Veterinary Anaesthesia (Tenth Edition)

PrefaceThis, the 10th edition of Veterinary Anaesthesia, is a direct descendant of Anaesthesia & Narcosis of Animals &Birds by Sir Frederick Hobday published in 1915 by Baillière, Tindall and Cox. The 1st edition of VeterinaryAnaesthesia, which had marked similarities to Hobday’s book, was written by Professor J.G. Wright andpublished in 1942. Wright’s intention was to ‘incorporate in a small volume the present status of knowledgeon anaesthesia in the domestic animals’. This he accomplished in 198 small pages with fewer than100 references to publications – including many to his own work. Since then tremendous advances havebeen made and now almost every week that passes sees new publications relating to veterinary anaesthesiaand its related subjects.Thus, we have had to acknowledge the impossibility of including a comprehensivebibliography in this edition, but we have selected references which should provide a usefulintroduction to the literature. In addition, we have indicated where attention should be given to materialpublished before computerized databases became available because, despite the increasing complexity ofanaesthesia, simple methods also work.Although extensively revised, the general concepts remain as in previous editions. The aim is still toprovide a text for undergraduate veterinary students, a reference work for veterinarians in general practiceand laboratory scientists, and a stimulating introduction to the subject for those wishing to specializein veterinary anaesthesia through the examinations of the Royal College of Veterinary Surgeons, theAmerican College of Veterinary Anesthesiologists and the European College of Veterinary Anaesthesia.Because we believe that clinical anaesthesia encompasses much more than an exercise in applied pharmacology,emphasis is still on the effects of clinically useful doses of drugs and of practical techniques in animalpatients, rather than on pharmacological effects demonstrated in healthy experimental animals inlaboratories.We wish to express our appreciation of the invaluable help given by Mrs Lorraine Leonard, librarian ofthe University of Cambridge Veterinary School, and the librarians at the Royal College of VeterinarySurgeons in tracing older references. Mr Stephen Freane of the Royal Veterinary College gave much assistancewith computer-generated figures. Finally, our warmest thanks are due to the publishers for theirpatience, and especially to Deborah Russell whose encouragement ensured completion of the manuscript.L.W. HallK.W. ClarkeC.M. Trim2000

General considerations 1INTRODUCTIONThe clinical discipline concerned with thereversible production of insensibility to pain isknown as ‘anaesthesia’, a term coined by OliverWendell Holmes in 1846 to describe a new phenomenonin a single word. It is essentially a practicalsubject and although becoming increasinglybased on science it still retains some of the attributesof an art. In veterinary practice anaesthesiahas to satisfy two requirements: (i) the humanehandling of animals and (ii) technical efficiency.Humanitarian considerations dictate that gentlehandling and restraint should always be employed;these minimize apprehension and protectthe struggling animal from possible injury.Technical efficiency is not restricted to facilitationof the procedure to be carried out on the animal, itmust also take into account the protection of personnelfrom bites, scratches or kicks as well as therisks of accidental or deliberate self-injection withdangerous or addictive drugs. Moreover, today itis considered that personnel need protection fromthe possible harmful effects of breathing low concentrationsof inhalation anaesthetic agents.While anaesthesia has precisely the same meaningas when it was first coined, i.e. the state inwhich an animal is insensible to pain resultingfrom the trauma of surgery, it is now used muchmore widely and can be compared to terms such as‘illness’ and ‘shock’ which are too non-specific tobe of real value. Starting with the premise that‘pain is the conscious perception of a noxious stimulus’two conditions may be envisaged: generalanaesthesia where the animal is unconscious andapparently unaware of its surroundings, and analgesiaor local anaesthesia where the animal, althoughseemingly aware of its surroundings, showsdiminished or no perception of pain.General anaesthesia is a reversible, controlleddrug-induced intoxication of the central nervoussystem in which the patient neither perceives norrecalls noxious or painful stimuli. Analgesia maybe produced by centrally acting drugs such asmorphine given in doses insufficient to produceunconsciousness or by substances having a local,transient, selective paralytic action on sensorynerves and nerve endings (local anaesthetics). Theanalgesia produced by these latter substances maybe classified as local or regional, applied as theyare by topical application, subdermal or submucousinfiltration and by peripheral, paravertebralor spinal perineural injection.The anaesthetist aims to prevent awareness ofpain, provide immobility and, whenever this isneeded, relaxation of the skeletal muscles. Theseobjectives must be achieved in such a way that thesafety of the patient is not jeopardized during theperianaesthetic period. Many animals fear andresist the restraint necessary for the administrationof anaesthetics thereby increasing not only thetechnical difficulties of administration but alsothe dangers inseparable from their use. A fullyconscious animal forced to breathe a strange and1

2 PRINCIPLES AND PROCEDURESpossibly pungent vapour struggles to escape andsympatho-adrenal stimulation greatly increasesthe risks associated with the induction of anaesthesia.For this reason, veterinary anaesthetistsoften employ sedative drugs to facilitate the completionof general anaesthesia as well as to overcomethe natural fear of restraint inherent inanimals and to control any tendency to move suddenlyduring operations under local analgesia.In addition, the veterinary anaesthetist mustrecognize that not only does the response of eachspecies of animal to the various anaesthetics differdue to anatomical and physiological differences,but that there is often a marked variation inresponse between breeds within each particularspecies. Another factor which must be consideredis that in many parts of the world veterinariansmust perform tasks without highly skilled assistanceand when employing general anaesthesia,after inducing it themselves, have to depute itsmaintenance to a nurse or even to a lay assistant.(It must be pointed out that in many countries,including the UK, the delegation of tasks related toanaesthesia to an untrained person may in law beconsidered negligent if a mishap occurs). Thus, thecontinued development in recent years of safe,simple, easily applied techniques of general anaesthesiaand regional analgesia, together with theinstitution of nurse and anaesthetic techniciantraining programmes, are particularly welcome.PAINCLASSIC TEACHING RELATING TO PAINAs anaesthesia is invoked to prevent appreciationof pain, any study of the discipline of anaesthesiamust be related to an understanding of what constitutespain. The old classic teaching on paininvolved a hard-wired, modality specific, line specific,single pathway which coupled stimulus withpain sensation. Anatomists labelled the axons andnerve cells according to this single relay transmissionsystem. It commenced in the periphery withfine myelinated (Aδ) and unmyelinated (C-fibre)afferents which possessed such high thresholds forstimulation that they only responded to noxiousstimuli. Sherrington (1900) termed these structures‘nociceptors’ but he realized that impulses in themwould not necessarily lead to pain sensationunless the central nervous system accepted themand conveyed them to a pain-perceiving region ofthe brain. The nociceptor fibres were found to endpreferentially on cells in laminae 1, 2 and 5 of thedorsal horn and from there impulses were believedto reach the thalamus by way of spinothalamicfibres which ran in the ventrolateral whitematter of the spinal cord. From the thalamusimpulses were said to reach a site of pure pain sensation(pain centre) in the association areas of thecerebral cortex.Afferent mechanismsIn recent years pain studies have resulted in analmost explosive expansion of knowledge relatingto pain mechanisms in the body and have shownthat these earlier ideas must be abandoned infavour of an interlocking, dynamic series of biologicalprocesses which need still further investigation.It is apparent that in the periphery the oldpicture of fixed property nociceptor cells in damagedtissue passively detecting the products of cellbreakdown does not accurately represent what isactually happening. The tissue breakdown productshave been shown to have both direct and indirecteffects on sensory afferent nerves. The roleof unmyelinated sensory fibres themselves ininflammation as proposed by Lewis (1942) is, however,now well established. Leucocytes attractedinto damaged tissues secrete cytokines which haveboth powerful systemic and local effects. Substancessuch as nerve growth factor synthetizedlocally in damaged tissue are also involved in painproduction (McMahon et al., 1995). The sympatheticnerves play a role in the inflammatoryprocess, new α adrenergic, bradykinin and opiatereceptors appear and there are a group of C-fibreswhich seem to be completely silent in normaltissue but which are activated by ongoinginflammation.It is now also clear that certain types of pain areproduced by afferents with large diameters outsidethe range of nociceptors. There is evidencethat secondary mechanical hyperalgesia, whichdevelops in healthy tissue surrounding injury or indistant tissue to which pain is referred, can be

GENERAL CONSIDERATIONS 3mediated by the thick tactile sensory fibres. Thesepains are probably provoked by impulses in normallow-threshold afferents entering the centralnervous system, where they encounter highlyabnormal central nervous circuits that amplify orreroute the signals of normally innocuous events.The afferent fibres convey information to thecentral nervous system in two quite differentways. Sensory fibres which have been changed bytheir contact with damaged or inflamed tissue dischargeimpulses in a characteristic spatial and temporalpattern. The second way is by transport ofchemicals from the tissues along axons towardsthe dorsal root ganglion. In response to changes inthese relatively slowly transported chemicals thechemistry and metabolism of the cytoplasm andcell membrane, including its central terminalarborizations, is altered. This consequently affectsthe post-synaptic cells of the central nervoussystem.Pain and the central nervous systemThe first cells of the central nervous system onwhich the afferents terminate are not exclusivelysimply relay cells. They form integrated groupswith both summation and differentiation functionsas well as inhibitory and facilitatory mechanisms.The facilitatory functions appear tobecome active following noxious inputs and thisresults in the development of a hyperalgesic state(Treede et al., 1992; Woolf & Doubell, 1994). Inaddition, there are also powerful inhibitory systemsin this region and their failure may contributeto hyperalgesia.The modulator role of the spinal cord in transmissionof nocioceptive signals from the peripheryto the brain has been known for many years, andnew evidence as to the complexity of the systemand both the excitatory and inhibitory influence ofmany different neurotransmitter substancesemerges continually (Dickenson, 1995, Marshet al., 1997). Knowledge of these pathways formsthe basis for the provision of pain relief by theepidural or intrathecal administration of analgesicdrugs. To date the opioid pathways remain themost important system involved in the productionof analgesia at the spinal level, although noradrenaline,the natural ligand acting at α 2 adrenoceptors,also has a major role in the spinal modulationof nocioception. Opioid receptors and α 2 adrenoceptorsare present in laminae 1 and 2 of the dorsalhorn, the area involved in the reception and modulationof incoming nocioceptive signals, and theirdensity and, in the case of opioid, the proportion ofeach type of receptor differ at different levels of thespinal cord (Bouchenafa & Livingston, 1987, 1989;Khan et al., 1999). The density of opioid receptors islabile, increasing in response to chronic pain(Brandt & Livingston, 1990; Dickenson, 1995), andchanging with age (Marsh et al., 1997).In both brain and spinal cord, a new receptorhas been identified which although sharing a highdegree of sequence similarity with opioid receptorsis not activated by opioids. This receptor wasnamed the ORL-1 (opioid receptor-like) receptor.Subsequently the endogenous peptide ligand forORL-1 was identified and named orphanin FQ ornociceptin. This peptide has a widespread distributionthroughout the nervous system. Despite itsstructural similarity to opioid peptides, nociceptin(which has now been synthesized) appears towork through entirely different neurological pathways,and it is thought that these pathways mightbe involved in the modulation of a broad range ofphysiological and behavioural functions (Meunier,1997; Darland & Grandy, 1998). In the midbrain theORL-1 receptor type has a dense to moderate levelof expression in the periaqueductal gray matter, anarea known to be involved with nocioceptive processing,and where electrical stimulation or opioidagonist agents will produce intense analgesia(Meunier, 1997; Darland & Grandy, 1998). In thespinal cord of the rat, ORL-1 receptors are found inthe superficial layers (laminae 1 and 2) of the dorsalhorn, in areas similar to those where opioidreceptors are located. The density of neuronesexpressing the ORL-1 receptor varies in differentareas of the spinal cord. The most recent work(unpublished results quoted by Darland &Grandy, 1998) suggests that these neurones areinternuncial neurones, and do not themselvesproject forward to the thalamus.The position of nociceptin in relation to analgesiais still unclear. From the anatomical locationsof the ORL-1 receptors it was anticipated that nociceptinwould cause analgesia by both spinal andsupraspinal mechanisms. In the whole animal,

4 PRINCIPLES AND PROCEDURESnociceptin does provide analgesia through spinalmechanisms, as intrathecal injection in rats produceda dose-dependent reduction of a spinalnocioceptive flexor reflex, and produced behaviouralantinocioception in the tail flick test. Theseeffects were not accompanied by sedation ormotor impairment, and could not be reversedby antagonists of the opioid, α 2 adrenoceptor agonistor GABA-A receptors, thus suggesting thatthey acted through a mechanism as yet unknown(Xu et al., 1996). However in rats and mice nociceptingiven by intracerebroventricular injectionunexpectedly antagonized the analgesic effects ofstress, opioids and electroacupuncture, thus suggestingthat the supraspinal actions of the peptidewere ant-analgesic. The apparent allodynia andhyperalgesia induced by the supraspinal effects ofnociceptin can be blocked by another naturallyoccurring peptide, which has been termed nocistatin(Okuda-Ashitaka et al., 1998; Darland &Grandy, 1998). Despite the complexity of the pathwaysinvolving the modulation of pain by nociceptin,interest continues in this field. Recent workhas concentrated on the production of antagoniststo nociceptin, as theoretically these may provideanalgesia by supraspinal mechanisms, and thereforebe more suitable as analgesic drugs in thepractical situation (Meunier, 1997). When comparedwith opioid analgesics, a major potentialadvantage of nociceptin-based compounds is that,to date, they have not been seen to cause behavioursuggestive of euphoria or dysphoria, andtherefore have the potential to become analgesicswith limited tendency for abuse.Increased understanding of the activities of theperipheral and first central cells has not beenaccompanied by similar advances in knowledge ofthe functioning of the deeper parts of the nervoussystem. There is considerable new knowledge ofthe way in which the brainstem exerts a descendingcontrol of the receptivity of the dorsal horncells (Stamford, 1995), but so far there is no understandingof the circumstances in which these controlscome into operation. The old idea of adedicated, localized pain centre is quite untenablebecause apart from massive excision of the inputstructures, no discrete lesion in the brain has everbeen shown to produce long-lasting analgesia.Thus it is necessary to analyse a distributed systemand until very recently methods to analyse brainsystems in a relatively non-invasive manner didnot exist.Investigation of brain systems involved in painEven the techniques now available to study activityin the brain have severe limitations. Singlephoton emission computed tomography (SPECT),positron emission tomography (PET) and functionalmagnetic resonance imaging (fMRI) provideindirect measures of local brain activity. Directmeasures of neural activity can be obtained frommagnetoencephalography (MEG) and electroencephalography(EEG). A critical review of all thesetechniques as applied to human subjects is that ofBerman (1995).SPECT, PET and fMRI measure changes inregional cerebral blood flow (rCBF) and the evidencethat links rCBF to increased neural activityas originally proposed by Roy and Sherrington(1890) is now well established. However, as pointedout by Berman (1995) there are important limitationsto the usefulness of these techniques.Temporal and spacial resolution are poor, beingmeasured in tens of seconds and several millimetres,while the final images are produced after multipleprocessing steps on large data sets sometimesobtained by pooling data from several subjects.MEG is limited to the cortical grey matter, the techniqueis very costly and requires a specially shieldedenvironment because the magnetic fields producedby the brain are of the order of 10 −13 Tesla,compared with 5×10 −5 Tesla for the earth’s magneticfield. The EEG has well known limitations ofcomplexity due to the difficulties inherent in accuratelyknowing the shape and conductivity of thedifferent tissues.It must be said that the application of functionalneuroimaging to pain is still of little value to theanaesthetist. There is much disagreement betweeninvestigators and the only reliable conclusionsseem to be that changes in activity in regions of thedi- and telencephalon are associated with painperception. These facts have been known fromother research methods for many years, some ofthem for more than a century, so that to date imagingmethods have done little more than reproduceolder findings. However, as these new,

GENERAL CONSIDERATIONS 5relatively or completely non-invasive methodsbecome established they promise to increase ourknowledge of cerebral pain mechanisms.CONTROL OF PAINIn experimental studies, acute pain behaviour orhyperexcitability of dorsal horn neurones may beeliminated or reduced if the afferent input is preventedfrom reaching the central nervous systemby pre-injury local anaesthetic block of afferentfibres or by dampening of the excitability of thecentral nervous system with opioids before itreceives an input from nociceptors (Woolf &Wall, 1986; Dickenson & Sullivan, 1987). Similarantinociceptive procedures are less effective whenapplied post-injury (Woolf & Wall, 1986a; Coderreet al., 1990). As a result, the importance of ‘timing’of the application of analgesic methods has beensuggested as a potential major factor in the treatmentof postoperative pain and the experimentalstudies would indicate a valuable role for preemptiveanalgesia in the prevention of postoperativepain.In contrast to the experimental findings, severalclinical studies in man (the only species where theduration and severity of pain can be relatively easilyestablished) have so far failed to demonstrateany marked superiority of pre-emptive analgesia.Only three studies have been somewhat positive infinding either a delay in request from the patient foradditional analgesics or a reduction in the need forpostoperative analgesics (Katz et al., 1992; Ejlersenet al., 1992; Richmond et al., 1993). Although it mustbe recognized that many of the clinical studieshave been non-randomized and otherwise poorlydesigned, there are likely to be good reasons forfailure to achieve similar results to those obtainedin experimental animals. Although central sensitizationmay contribute to postoperative pain inhumans, surgical trauma differs from the type ofstimulus used in most experimental animals.Contrary to a well localized thermal or chemicalinjury, or brief C-afferent fibre stimulation, theafferent input to the central nervous system duringand after surgery is prolonged and extensive withmixed cutaneous, muscular and visceral components.Central stimulation may persist in thepostoperative period because of continuinginflammation and hyperalgesia at the site of thewound; the analgesic methods have not been continuedinto this period. Moreover, conventionalpostoperative analgesia with local anaesthetics oropioids may not provide total C-afferent blockduring surgery.In human subjects it is useful to define pain asthat state that disappears when treated for pain. Itwould, therefore, seem useful to call a drug ananalgesic for an animal if it appears to amelioratethe reaction of an animal to what in man would beperceived as pain. However, it is most importantto be certain that the treatment has not merely preventedthe animal from displaying the sign usedby the observer to connote pain in that animal. Anextreme example would be to paralyse the animalwith a neuromuscular blocking drug. Abolition ofa clinical sign may be even more subtle. For example,neurectomy is commonly used to prevent ahorse from limping. In man this technique isknown to lead to Charcot joints and a deafferentationsyndrome, two signs that the unfortunatehorse may not be able to exhibit. Even in man,therapy is not a guaranteed test because there areintractable pains that fail to respond to any knowntherapy. There is no obvious reason to supposethat similar conditions do not exist in animals.Furthermore, because of the differing neurotransmittersand structures and behavioural repertoiresit could be that effective analgesics for human subjectsare not necessarily effective in all animals(Wall, 1992).It must be concluded that before clinical recommendationsof pre-emptive analgesia can be suggested,well controlled investigations in bothanimals and man are imperative. In the future,effective pre-emptive analgesia may well beachieved by a multimodal technique, such as acombination of opioids and neural block, or withspecific drugs acting at the spinal cord, such asNMDA antagonists, etc. rather than a singlemodality ‘pre-emptive’ treatment. There is a needto establish the exact role of post-injury neuroplasticityrelative to the magnitude and duration ofpostoperative pain and to develop simple and reliablemethods for clinical measurement of neuroplasticity.It is naive to believe that one analgesic orone single technique will solve the complex problemof postoperative pain. However, research and

6 PRINCIPLES AND PROCEDURESdevelopment of new analgesics acting at theperipheral site of injury, such as the NSAIDs, maylead to a reduction of side effects currently associatedwith postoperative pain relief. It is now wellestablished that prostaglandins contribute notonly to peripheral but also to central sensitization,and that NSAIDs act at peripheral and centralsites. Intrathecal administration of NSAIDs resultsin antinociception in experimental models of centralsensitization (Malmberg & Yaksh, 1992; 1992a)and their central action is equally effectivewhether given before or after the application of thenoxious stimulus. This is because they act on intracellularmessengers responsible for the maintenanceof the persistent nociceptive state in thespinal cord (Coderre & Yashpal, 1994). If the concentrationof NSAID in the brain continues toincrease for some hours after its administrationthis could provide analgesia covering much of theimmediate postoperative period (Hudspith &Munglani, 1996).MECHANISMS OF ANAESTHESIAIn 1906 Sherrington stressed the importance of thesynapse in central nervous system (CNS) processing.Since then details of synaptic transmissionwithin the CNS have received much attention.Studies have shown that a nerve cell receives informationby way of synaptic contacts all over thedendrites and cell body (Fig. 1.1). Impulses travellingin presynaptic fibres progress to the terminalbranches to depolarize the nerve endings. This depolarizationopens voltage-gated calcium (Ca 2+ )channels and the influx of calcium into theterminal. The resulting increase in intracellularcalcium triggers the exocytotic secretion of transmittersubstance from the nerve terminal. Thereleased transmitter diffuses across the synapticcleft and binds to specific receptor sites on the postsynapticmembrane. Receptor activation results ina change in permeability of the cell membrane toparticular ions, which in turn leads to changes inmembrane potential and to excitation or inhibitionof the postsynaptic neurone depending on thenature of the synapse, i.e. excitatory or inhibitory.This voltage gated activity is generally acceptedbut it is now known that there is no clear distinctionbetween voltage modulated channels and ligandgated channels. The demonstration of intermediateforms of ion channels suggests that overallcellular effects are far more complicated than wasthought to be the case as little as 25 years ago.FAST AND SLOW SIGNALLINGThe receptors linked directly to ion channels arefor fast signalling but synaptic stimulation mayresult in a more subtle long term modulation ofexcitability via second messengers. For example,noradrenaline interacts with two different classesof receptors (Pfaffinger & Siegelbaum, 1990). Oneclass activates adenylate cyclase (β adrenoceptors)and the other inhibits adenylate cyclase (α adrenoceptors).Similarly, the response of muscarinicacetylcholine receptors depends on the receptorsubtype. M1, M3 and M5 receptors activate phospholipaseC and generate diacylglycerol and inositoltriphosphate (IP3), while M2 and M4 receptorsare associated with inhibition of adenylate cyclase(Fukuda et al., 1989). Many other neurotransmitters,such as dopamine and 5-hydroxytryptamine,are now thought to activate second messengersystems inside the cell.Both fast and slow synaptic events eventuallymodulate specific ion channels and alter the levelof excitability of postsynaptic neurones. Nerve terminalsthemselves are subject to modulation bypresynaptic axonal contacts by way of presynapticinhibition (Schmidt, 1971). Also, axons branch andchanges in threshold at each branch point mayresult in different patterns of impulse activity indifferent nerve branches. Thus, there are both temporaland spatial patterns of neuronal activity inthe CNS.ACTION OF GENERAL ANAESTHETICAGENTSAt concentrations likely to be found in the brainduring surgical anaesthesia general anaestheticsdepress excitatory synaptic transmission. Theeffects of anaesthetics on inhibitory synaptic transmissionare more varied and both depressionand enhancement of inhibition have been reported.From the above brief account of synapticprocessing, it is clear that anaesthetics may act

GENERAL CONSIDERATIONS 7at a number of different sites either enhancinginhibition or depressing excitation at them.Depression of excitation or enhancement of inhibitionwill reduce transmission through a synapticrelay.Excitation may be depressed by:1. Slowing of action potential propagation2. Enhancement of presynaptic inhibition3. Depression of release of transmittersubstances4. Depression of the response of postsynapticreceptors5. Enhancement of postsynaptic inhibition byincreased release of inhibitoryneurotransmitters6. Augmentation of the response ofpostsynaptic receptors to inhibitoryneurotransmitters7. Direct action on postsynaptic neurones tomodulate excitability8. Modulation of the resting cell membranepotential.It is clear that the action of general anaesthetics islikely to be complex. Moreover, the usual chemicalstructure/activity relationship seen with mostTerminalarborizationDendritic treeAfferent axonCell bodyPresynapticinhibitory axonExcitatorysynapsesInhibitorysynapseInhibitoryinterneuroneAxon colateralFIG.1.1 Schematic diagram of the organization of asynaptic relay within the CNS.bioactive chemicals is conspicuously absent inanaesthetics. There is a very wide range in molecularstructure ranging from relatively simple chemicals(e.g. cyclopropane) to complex steroids (e.g.alphaxalone) which may, if conditions are appropriate,lead to a state of anaesthesia. Although convulsantsmay antagonize some anaesthetics theonly effective antagonist for all is very great ambientpressure. Pressure provides a physicochemicalbarrier to an anaesthetic by action at a putativehydrophobic receptor site: it seems that pressureprevents the normal increase in volume caused byan anaesthetic at the receptor site.There is still argument over whether anaestheticshave a common mode of action or whethereach agent has a unique action, the end result ofwhich is to produce a state of anaesthesia. Thesimplicity of the idea of a common mode of actionis more appealing but is yet to be established. Oneof the more attractive unifying hypotheses is thatvoltage sensitive Ca 2+ channels are the targets forall anaesthetic agents since this cation contributesto the regulation of neuronal excitability andneurotransmitter release through at least threedifferent types of voltage sensitive Ca 2+ channel(Hirota & Lambert, 1996). However, general anaestheticsdiffer in their effects on distinct neuronalprocesses and even their isomers do so, thus a nonspecificunitary mechanism is unlikely.Natural sleep and general anaesthesiaIt is interesting to compare general anaesthesiawith natural sleep. Some 40 years have passedsince the first recognition of rapid eye movement(REM) sleep (Aserensky & Kleitman, 1953) and thelinking of this to Moruzzi and Magoun’s earlierfinding in 1949 of the arousal-promoting brainstem network – the ascending reticular activatingsystem. Later, in 1962 Jouvet discovered that thepontine reticular formation played a key role inREM sleep generation. It has since been shownthat REM sleep is regulated, at least in part, bymuscarinic cholinergic receptors of the non-M1variety localized within the medial pontine reticularformation (Steriade & McCarley, 1990). Animalstudies have shown that the injection of minutedoses of morphine into the medial pontine reticularformation known to be involved significantly

8 PRINCIPLES AND PROCEDURESinhibited REM sleep and increased the occurrenceof apnoea (Keifer et al., 1992). Even more recentlyin vivo microdialysis studies have shown that systemicallyadministered morphine significantlydecreases release of acetylcholine in the medialpontine reticular formation (Lydic et al., 1993). Similarresults have been reported for anaesthetic concentrationsof the inhalation anaesthetic, halothane(Keifer et al., 1994). Thus, cholinergic neurotransmissionin the pontine reticular formation is alteredby morphine, halothane and REM sleep. Thisgives rise to the view that cholinergic transmissionin pontine reticular formation may generate someof the phenomena associated with morphineeffects and halothane anaesthesia.Although there are serious reservations aboutthe use of the EEG as an index of anaesthesia(Prys-Roberts, 1987; Hug, 1990; Kulli & Koch,1991; Kissin, 1993) both halothane and naturalsleep produce similar spindles in the cortical EEGsuggesting that halothane spindles and naturalsleep spindles may be generated by the same thalamocorticalmechanisms (Keifer et al., 1994).Further reseach in this area may prove productivebut to date the fact remains that anaestheticsare one of the few groups of drugs which are usedclinically without any real understanding of theirunderlying activity and the reason for their amazingefficacy remains a mystery.DEPTH OF ANAESTHESIAOnly two years after the first demonstration ofgeneral anaesthesia John Snow (1847) stated, quiteemphatically, that the point requiring most skill inthe administration of anaesthetics is to determinewhen it has been carried far enough. Snowdescribed five stages of anaesthesia produced bydiethyl ether, the last stage in his experiments withanimals being characterized by feeble and irregularrespiratory movements heralding death – clearlya stage too far. A major problem faced by allanaesthetists since that time is to avoid both ‘toolight’ anaesthesia with the risk of sudden violentmovement, and the dangerous ‘too deep’ stage.Snow suggested guidelines whereby anaesthetistscould reduce the risk of either too light or too deepether anaesthesia. In the First World War the USArmy in France was seriously deficient in medicalofficers with any experience of anaesthesia and tohelp the inexperienced doctors avoid some of thedangers Guedel in 1918 devised a scheme involvingobservation of changes in respiratory rate,limb movement and eye signs which formed thebasis of his celebrated ‘Signs and Stages of EtherAnaesthesia’ which has been included until veryrecently in all text books of anaesthesia.The introduction of neuromuscular blockingdrugs after World War II completely changed thepicture and the emphasis swung from the dangerof too deep anaesthesia to that of too light anaesthesiawith the risk of conscious awareness andperception of pain. Cullen et al. (1972), in anattempt to produce new guidelines indicatingdepth of anaesthesia, were forced to conclude thatit was difficult to categorize the clinical signs ofanaesthesia for any one inhalation anaesthetic letalone for inhalation agents in general. Today avery much broader range of different drugs areemployed during anaesthesia than were used inthe 1970s. These drugs produce a very wide spectrumof quite separate pharmacological actionswhich include analgesia, amnesia, unconsciousnessand relaxation of skeletal muscles as well assuppression of somatic, cardiovascular, respiratoryand hormonal responses to surgical stimulation.It is believed from observations in man thatloss of conscious awareness is achieved at lighterdepths of anaesthesia than are needed to preventmovement.Electroencephalography (EEG)The majority of comprehensive studies attemptingto monitor the depth of anaesthesia have focussedon the use of the EEG. However, the raw EEG is ofvery limited value to the clinical anaesthetistbecause of wide differences in response with differentanaesthetics, the long paper runs utilized forrecording generating unmanageable amounts ofpaper, and subjective interpretation of the tracesobtained. The fast-moving EEG signals cannot beeffectively monitored on visual display unit(VDU) as can the electrocardiogram and in orderto simplify the extraction of useful informationfrom complex waveforms a number of methods ofcompressing, processing and displaying EEGsignals have been developed, some of which have

GENERAL CONSIDERATIONS 9been compared by Levy et al. (1980) and Stoeckelet al. (1981). In attempts to simplify the procedurethese techniques have, in many cases, beenapplied to single channels of EEG rather than the16 channels normally studied.It is only possible to describe the EEG changesrelated to anaesthesia in the most general terms.The earliest changes seen with the induction ofanaesthesia are that a previously responsive αrhythm becomes unresponsive and then desynchronizedand flattened, becoming replaced withhigh frequency activity of low or high voltagedepending on the agent. Further deepening ofanaesthesia is associated with replacement ofthese waves with slow waves and the slower thefrequency the deeper the level of anaesthesia(Mori et al., 1985). Further deepening of anaesthesiaproduces periods of electrical silence interruptedby bursts of activity. The bursts may be of a fewslow waves or with other agents repetitive highvoltage spikes or even the ‘spike and dome’ complexesthat characterize epileptic fits. This ‘epileptoid’activity has commonly been associatedwith enflurane but it is charcteristic of ethers (Joaset al., 1971).Power spectrum analysisIn this technique the EEG signal, after being digitized,is subjected to fast Fourier analysis inwhich it is separated into a series of sine waves,%/Hz80the sum of which represents the original signal.Breaking up the original waveform in thisway makes it possible to compare one nonstandardwave form with another and, in particular,to extract the distribution of components ofdifferent frequency within the EEG signal. Thepower in each frequency band is then derived bysquaring the amplitude of each sine wave intowhich the Fourier Transform has separated theoriginal signal. Power spectrum analysis as ameans of monitoring depth of halothane anaesthesiain horses has been reported by Otto and Short(1991).Considerable ingenuity has been devoted todisplaying the three variable data derived fromthe EEG by power spectrum analysis (Figs 1.2 &1.3). Methods such as power spectrum analysisdemonstrate the relative partitioning of changesassociated with depth of anaesthesia as shown inthe unprocessed EEG in the general shift to lowerfrequency but even so they are cumbersome and oflimited clinical application. The averaging overtime needed for all the various methods is relativelylong with a great loss of resolution.Important changes of a transient nature in theEEG such as those associated with arousal andburst suppression may be completely obscured(Bimar & Bellville, 1977). Thus it seems that inthe typical clinical environment, in which multipledrugs are administered and clinical end-pointsare not defined clearly, the success achieved inTime (min)300 00.5FIG.1.2 Plot of compressed spectral array of EEG power spectrum.(After Stoeckel & Schwilden,1987).In this plot it isnecessary to suppress the lines behind the hillocks (high power bands) of the plot so that information hidden behind thehillocks is lost.To avoid loss the time axis is at an angle to the other two axes but this only slightly improves the visibility ofthis lost information.20 Hz

10 PRINCIPLES AND PROCEDURESFrequency (Hz)2000determining the depth of anaesthesia and predictingintraoperative arousal with movement, bystudy of EEG variables, is limited.Cerebral function monitoringA number of methods of analysing the EEG signalhave been used in attempts to extract from it a singlenumber which might be related to the depth ofanaesthesia. The median frequency and the numberof times the signal crosses the isoelectric line ina fixed time have been suggested but have notproved to be useful. The cerebral functionanalysing monitor (CFAM) of Maynard andJenkinson (1984) is a development of the cerebralfunction monitor (CFM) described by Maynard in1969. The CFM filtered the EEG signal anddisplayed the average peak voltage on a slowlymoving chart to facilitate trend analysis. and wasof particular value as a monitor of cerebral perfusion.In the CFAM similar signal processing isemployed; after filtering to increase amplitudewith frequency and logarithmetic amplitude compression,the frequency distribution is displayeddivided into the four conventional EEG frequencybands. This instrument may be used to displaytransient EEG events and to study evoked potentials.References to the the use of the CFAM aregiven by Frank and Prior (1987).Evoked responsesTime (min)FIG.1.3 Spectral edge frequency plot.This plotdemonstrates the frequency below which lies 95% of thepower in the EEG signal.(After Rampil et al.,1980.)Evoked responses are changes in the EEG producedin the EEG by external stimuli, surgical1or otherwise. Anaesthetic depth is a balancebetween cerebral depression and surgical (orother) stimulation. Thus, cerebral function duringanaesthesia is most easily assessed by putting in astimulus – auditory or somatic or visual – andobserving the EEG response. That response canthen be compared for amplitude and latency withthe response to the same stimulus in the presenceof differing brain concentrations of any anaesthetic.Changes in the EEG produced by external stimuli(evoked responses) are not easy to detect becausethey may be as much as 100 times below normalEEG noise and the technique of signal averagingmust be employed. A repetitive stimulus such asclicks in the external ear canal is applied to thesubject and an epoch of EEG signal is summatedin such a way that the normal EEG signal is cancelledout (because it is random). The evokedresponse is time-locked to the stimulus and reinforcesitself by repetition. The auditory evokedresponse (AER) is usually summated over 2000 ormore epochs, taking 5 to 7 minutes, and this is alimitation of the technique since transient changesmay not be detected. The AER can be tracked fromits entry into the brain stem via the auditory nerveto the auditory cortex and cortical associationareas and the pathway continues to function duringquite deep surgical anaesthesia.There are two ways of producing the AER: thetransient method and the steady state method. Themiddle latency part of the transient response refersto a series of one to three bipolar waves occurringin the first 100 ms after an abrupt auditory event.This middle latency response (MLR) or ‘early corticalresponse’ represents processing at the primaryauditory cortex and is elicited using clicks atrates near to 10/s. Although rates of as few as 1/sproduce larger MLR responses, they take a verylong period of signal averaging in order to producea satisfactory waveform. The transient MLRis promising but the time to produce the response(about 5 min) and difficulties in interpreting thewaveforms mean that it is very limited as a clinicaltool. In contrast, the steady state method refers toactivity in the EEG driven by a train of stimulidelivered at a sufficiently fast rate to cause responsesprovoked by successive stimuli to overlap.At rates of stimulation near to 40 Hz theamplitude reaches a maximum and with all gen-

GENERAL CONSIDERATIONS 11Air0.4% Isoflurane0 10 20 30 40 50Frequency (Hz)0 10 20 30 40 50Frequency (Hz)FIG.1.4 Coherent frequency of the auditory evokedpotential.(After Mungliani et al.,1993.) The coherentfrequency is derived by a mathematical process whichdemonstrates the power of the fundamental (which islarge compared with the power in the harmonics).eral anaesthetics the 40Hz value of the dominantfrequency decreases with anaesthetic depth(Mungliani et al., 1993), as illustrated in Fig. 1.4.Somatosensory evoked potentials (SER or SEP)are usually produced by percutaneous stimulationof a peripheral nerve and the waveform of theevoked potential depends on the site of stimulationand the positions of the cranial electrodes.Again the technique suffers from the time requiredto obtain a signal; averaging over 4 to 8 minutesmay be necessary and this obscures transient EEGchanges which may be produced by surgicalstimulation.The effect of surgical stimulation in horsesunder isoflurane anaesthesia has been examinedby Otto & Short (1991). These workers looked atthe power spectrum between 1 and 30 Hz andcalculated the 80% spectral edge frequency (80%quantile; SEF 80), median power frequency (50%quantile; MED), relative fractional power locatedin the delta (1 to 4Hz), theta (4 to 8Hz), alpha (8 to13Hz), beta (13 to 30Hz) frequency band and thebeta/delta ratio (BD), the theta/delta (T/D) andalpha/delta (A/D) ratio. They concluded that themeasured EEG variables A/D ratio, median powerfrequency and the 80% spectral edge frequencyrecorded in horses with an end-tidal concentrationof 1.7% isoflurane were significantly increased bysurgical stimulation, suggesting EEG arousal bythis stimulation.New techniques are now being developedusing bandpass digital filtering and automaticpeak detection to decrease greatly the time neededfor the averaging process (Bertrand et al., 1987).The Bispectral Index (BIS) has been developedby Aspect Medical Systems as a monitor ofthe state of cortical arousal and gives a number of0 to 100 depending on the degree of wakefulnessof the subject. A low BIS may occur with sleep,anaesthesia and head injury (Driver et al., 1996).The BIS uses both the EEG frequency and phase inits computation but the exact process remains, atthe moment, a jealously guarded commercialsecret.More technologies for study of depth of anaesthesiaare currently available than at any time inthe past but whether any of them will become clinicallyuseful may well be governed by the degree ofcommercial investment they obtain. To be of use inclinical practice the technology must be presentedin monitors that are easy to apply and simple tooperate. Many potentially useful technologies willdisappear without the balance of academic studyand commercial interest being available to assessthem (Pomfrett, 1999).THE ‘CLASSIC’ SIGNS OF ANAESTHESIAThe so-called ‘classic signs’ of anaesthesia, such astabulated in Chapter 2 for convenience of newcomersto the subject and in older textbooks ofanaesthesia, were provided by the presence orabsence of response of the anaesthetized subject tostimuli provided by the anaesthetist or surgeon.Particular signs of anaesthesia were, therefore,equated with particular anatomical levels or‘planes’ of depression of the central nervous system.These signs were often likened to a series oflandmarks used to assess the progess made on ajourney. Such empirical, traditional methods ofassessing the progress of anaesthesia and the

12 PRINCIPLES AND PROCEDURESanatomical implications that went with thesemethods incorporated a fallacy, because theytook no account of the fact that the changing functionof any biological system can only be made interms of magnitude and time. A depth of unconsciousnessis really a particular moment in a continuoustemporal stream of biological orneurological phenomena to be interpreted by themagnitude and quality of these phenomenaobtaining to that moment.Use of the term ‘depth of anaesthesia’ is nowso ingrained in common usage that it must beaccepted since it probably cannot be eradicated. Itis important, however, to realize that it commonlyrefers to depression of brain function beyond thatnecessary for the production of ‘anaesthesia’, i.e.unawareness of surroundings and absence ofrecall of events.In general, the volatile anaesthetic agentshalothane, enflurane, isoflurane, sevoflurane anddesflurane produce a dose-dependent decrease inarterial blood pressure and many veterinaryanaesthetists use this depression to assess thedepth of anaesthesia. The effect is not so markedduring anaesthetic techniques involving theadministration of opioid analgesics and nitrousoxide. If the depth of unconsciousness is adequate,surgical stimulation does not cause any change inarterial blood pressure. There are, however, manyother factors which influence the arterial bloodpressure during surgery such as the circulatingblood volume, cardiac output and the influence ofdrug therapy given before anaesthesia. If ketamineor high doses of opioids are given arterial bloodpressure may change very little if the depth ofunconsciousness is increased by the administrationof higher concentrations of inhalation anaesthetics.Changes in heart rate alone are a poor guide tochanges in the depth of unconsciousness. Theheart rate may increase under isoflurane andenflurane anaesthesia due to their direct effect onthe myocardium. Arrhythmias are common duringlight levels of unconsciousness induced byhalothane, when they are usually due to increasedsympathetic activity. In general, however, tachycardiain the absence of any other cause may betaken to represent inadequate anaesthesia for theprocedure being undertaken.Anaesthetic agents affect respiration in a dosedependentmanner and this was responsible forthe original classification of the ‘depth of anaesthesia’.In deeply anaesthetized animals tidal andminute volumes are decreased but, depending onthe species of animal and on the anaesthetic agentsused, respiratory rate may increase before breathingeventually ceases once the animal is closeto death. As inadequate anaesthesia also is oftenindicated by an increase in the rate and/or depthof breathing the unwary may be tempted toadminister more anaesthetic agent to the deeplyanaesthetized animal in the mistaken impressionthat awareness is imminent. Laryngospasm,coughing or breath-holding can indicate excessiveairway stimulation or inadequate depth of unconsciousness.All anaesthetic agents, other than the dissociativedrugs such as ketamine, cause a dose-relatedreduction in muscle tone and overdosage producescomplete respiratory muscle paralysis. Inthe absence of complete neuromuscular block producedby neuromuscular blocking drugs thedegree of muscle relaxation may, therefore, usuallybe used as a measure of the depth of anaestheticinducedunconsciousness. However, even in thepresence of muscular paralysis due to clinicallyeffective doses of neuromuscular blockers it is notuncommon to observe movements of facial muscles,swallowing or chewing movements inresponse to surgical stimulation if the depth ofunconsciousness becomes inadequate.When animals are breathing spontaneouslythere are several signs which are generally recognizedas indicating that the depth of unconsciousnessis adequate for the performance of painfulprocedures, i.e. the animal is unaware of the environmentand of the infliction of pain – it is anaesthetized.Sweating (in those animals which do)and lacrimation may both occur if surgical stimulationis intense while the depth of unconsciousnessis too light. However, drugs that modifyautonomic effects, such as the phenothiazinederivatives (e.g. chlorpromazine or acepromazine)may also modify sweating responses.Unfortunately, there are many differencesbetween the various species of animal in the signswhich are usually used to estimate the depth ofunconsciousness. One fairly reliable sign is that of

GENERAL CONSIDERATIONS 13eyeball movement, especially in horses and cattle,although even this may be modified in the presenceof certain other drugs, such as the α 2 adrenoceptoragents (see ch. 11 on equine anaesthesia).Fortunately for the animal this test involvesinspection only and no touching of the delicatecornea and conjunctiva although it may be necessaryto separate the eyelids because these are usuallyclosed. Unless neuromuscular blocking drugsare in use very slow nystagmus in both horses andcattle and downward inclination of the eyeballs inpigs and dogs usually indicates a satisfactory levelof unconsciousness and, at this level, breathingshould be smooth although its rate and depth mayalter depending on the prevailing severity of thesurgical stimulation. Nystagmus is also seen inhorses just before death from hypoxaemia.Absence of the lash or palpebral reflex (closure ofthe eyelids in response to light stroking of the eyelashes)is another reasonably reliable guide to satisfactoryanaesthesia. In dogs and cats it is safe toassume that if the mouth can be opened withoutprovoking yawning or curling of the tongue, centraldepression is adequate. In all animals salivationand excessive lacrimation usually indicate areturning awareness.Disappearance of head shaking or whiskertwitching in response to gentle scratching of theinside of the ear pinna is a good sign of unawarenessin pigs, cats, rabbits and guinea pigs. Pupilsize is a most unreliable guide to unawarenessbecause a dose of an opiate tends to cause constrictionof the pupils while atropine causes dilation.The pupils do, however, dilate when an overdoseof an anaesthetic has been given or when awarenessis imminent.The experienced anaesthetist relies most of thetime on an animal’s response to stimuli producedby the surgeon or procedure to indicate adequatedepth of unconsciousness. The most effectivedepth is taken to be that which obliterates the animal’sresponse to pain and/or discomfort withoutdepressing respiratory and circulatory function.Computer controlled anaesthesiaIn general, anaesthetists use ‘rules of thumb’ whenmanaging the course of anaesthesia. As the anaestheticadministration proceeds, changes in the animal’sphysiological state are monitored by theanaesthetist who adjusts the rate of administrationof intravenous drugs, or the concentration of theadministered inhalation anaesthetic, or the lungventilation, as appropriate for the perceived stateof anaesthesia. The extent and direction of theadjustment is determined by this ‘rule of thumb’but this does not preclude the provision of safe andeffective anaesthesia. Every anaesthetist probablyuses some type of rules, but sometimes simplerules are hidden by an aura of profundititydesigned to enhance the mystique of anaesthesia.A computer may assist in dispelling this mystique.Given the availability of the necessary hardwareand computer software a computer can beused to control the administration of an anaesthetic.It may be programed to respond to a set deviationfrom some predetermined value measured bya sensor, which is considered by the anaesthetist tobe ‘normal’, by inducing a change in the deliveryof an agent. For example, the instructions may be‘If the arterial blood pressure decreases by10 mmHg then decrease the rate of administrationof halothane by 10%’. It is relatively easy to programthe computer to do this but a human anaesthetistcontrolling an anaesthetic administrationwill not respond in such a precise way. More likelya rule of thumb such as ‘If the arterial blood pressuredecreases slowly, then the rate of administrationof the anaesthetic needs to be decreased alittle’ will be applied by the anaesthetist. This isbecause humans have no difficulty in respondingto such imprecise information as ‘decreases slowly’or ‘a little’ but there is currently no freely availablecomputer language to describe suchimprecise data in such a way that a computer iscapable of acting on it.Accurate control of arterial pressure (or indeedany variable) in any anaesthetized animal imposesthe task of frequent monitoring of arterial pressureand adjustments of the rate of anaesthetic administration.Manual methods can lead to poor controlwith see-sawing values. Automatic closed-loopcontrol of anaesthetic delivery systems, developedto improve the quality of control using standardengineering systems of self-tuning algorithmsrelying on mathematical models of the cardiovascularsystem, are not much better because the cardiovascularsystem is complex. Much of the

14 PRINCIPLES AND PROCEDURES10075Set membership (%)25VerylowLow High Very highNormal020 80 120 160 200 220Systolic arterial pressure (mmHg)FIG.1.5 Subdivision of systolic arterial blood pressure into sets using fuzzy logic.The boundaries of each set form atriangle and overlap the boundaries of neighbouring sets.The shaded area shows the extent of the ‘normal’ set.(AfterAsbury & Tzabar,1995.)complexity arises from the fact that the response isnon-linear and involves a time delay before itoccurs, while the degree of responsiveness maychange with time.A key to solve this problem was provided byLofti Zadeh (1965) who coined the term ‘fuzzysets’. This concept says that an item (e.g. a measurementof blood pressure or a blood gas value)can belong simultaneously to several sets to differentdegrees, from not belonging (or 0% membership)through to totally belonging (or 100%membership) to a set. This principle has been wellexplained in relation to anaesthesia by Asbury &Tzabar (1995). They point out that a set of meanarterial blood pressure measurements from 20 to220mmHg can be assigned into sets such as ‘normal’,‘very low’, ‘high’, etc. Using classic logic eachvalue then takes on 100% membership of one andonly one set. This logic becomes less reasonablewhen 99 mmHg is interpreted as ‘low’ but100 mmHg as ‘normal’. When the values are dividedinto fuzzy sets where the ordinate indicates theextent of membership, each value can belong toone or more sets (but usually two sets). Thus avalue of 85 mmHg can be seen as belonging 75% toa set termed ‘low’ and at the same time 25% to a settermed ‘normal’ (Fig. 1.5). This gives a way ofexpressing imprecise information in a form whichcan be incorporated into a computer program.Using fuzzy logic control (Ying et al., 1992)which employs a series of rules described inimprecise terms (e.g. ‘If the arterial pressure isslightly above the desired range, increase theadministration rate of the anaesthetic a little’ or ‘Ifthe arterial pressure falls catastrophically stop theadministration temporarily’) leads to muchsmoother control. These rules would be formulatedby questioning an expert anaesthetist so that anengineer can convert the rules and imprecise datainto a computer program which fuzzifies theincoming blood pressure data from the measuringdevice, applies the rules and then calculates adefinitive administration rate (defuzzification)and automatically sets it on the anaesthetic deliverysystem.The difficulty with fuzzy logic is that its ruleshave to be extracted from experts who, thoughperhaps highly efficient in clinical work, do notrealize the extent of their own knowledge and particularlyhow their knowledge is structured. Anengineer then needs to optimize the rules andboundaries of fuzzy sets for best performance. Intheory, application of fuzzy logic should alwaysresult in much smoother and better controlled

GENERAL CONSIDERATIONS 15anaesthesia. The use of fuzzy logic control is likelyto grow but its development is both time-consumingand costly.MINIMAL ALVEOLAR CONCENTRATION(MAC) AND MINIMUM INFUSION RATE(MIR)Recognition of the problems in establishing thatthe patient is unconscious at any given moment,coupled with the difficulty of reproducing thesame degree of central nervous depression onanother occasion, forces the anaesthetist to rely onthe concept of minimal alveolar concentration(MAC), sometimes also known as minimal anaestheticconcentration, as proposed by Merkel andEger (1963). MAC is defined as the alveolar concentrationof an anaesthetic that prevents muscularmovement in response to a painful stimulus in50% of the test subjects. If adequate time is allowedfor the anaesthetic in the brain to equilibrate withthe anaesthetic agent in the blood, the alveolar partialpressure of the anaesthetic (which can bemeasured) is a reasonably accurate expression ofthe anaesthetic state. The stimulus, standardizedas far as possible, usually consists of tail clampingor an electrical stimulus in animals or surgical incisionor an electrical stimulus in man.The measurement of MAC enables the relativepotencies of anaesthetics to be compared, and withthe MAC defined as 1.0, the level of central nervousdepression can be stated as the ratio of alveolarconcentration to the MAC. This reproduciblemethod may be contrasted with the difficulty inusing physiological parameters as an indication, orthe EEG, which varies according to the agent used.Although the MAC value represents the anaesthetizingdose for only 50% of subjects the anaesthetistcan be reasonably certain that increasing thealveolar concentration to between 1.1 or 1.2 timesMAC will ensure satisfactory anaesthesia inthe vast majority of individuals because thedose–response curve is relatively steep. In veterinarypractice it is also important to note thataccording to Eger, the variability of MAC isremarkably low between species and is quite constantin any one animal. Finally, it is important toremember that MAC is determined in healthy animalsunder laboratory conditions in the absenceof other drugs and circumstances encounteredduring clinical anaesthesia which may alterthe requirement for anaesthesia. MAC is notaffected by the duration of anaesthesia, hyperkalaemia,hypokalaemia, hypercarbia or metabolicacid–base changes. However, MAC is reduced by8% for every °C reduction in body temperature, byhyponatraemia and with increasing age. In dogs aprogressive reduction of halothane MAC has beenshown to occur as mean partial pressure isreduced to 50 mmHg. Young animals have highMAC values, and hyperthermia also increasesMAC. MAC is measured as vol%, and so isdependent on atmospheric pressure, thus explainingthe increased doses of volatile agents requiredto maintain anaesthesia at high altitudes (Eger,1974; Quasha et al., 1980).The accurate control of depth of unconsciousnessis more difficult to achieve with intravenousanaesthetic agents. To obtain unconsciousnessthey must be administered at a rate which producesa concentration of drug in the bloodstreamsufficient to result in the required depth of depressionof the central nervous system. The concept ofminimum infusion rate (MIR) was introduced bySear and Prys-Roberts in 1970 to define the medianeffective dose (ED 50 ) of an intravenous anaestheticagent which would prevent movement in responseto surgical incision. Unlike MAC, however, MIRdoes not necessarily equate with the concentrationof the anaesthetic in the blood (Spelina et al., 1986).In veterinary anaesthesia there is a paucity of informationrelating to the MIR and since there is noway of estimating the concentration of the agent inthe blood sufficiently rapidly to enable the anaesthetistto adjust the rate of administration duringany operation in the light of the analytical result, itsusefulness is questionable. It may be of value in settinginfusion rates in computer controlled intravenousanaesthesia but such techniques currentlyappear to be used infrequently in veterinary practicealthough it is possible that their use in experimentallaboratories is more widespread.ANAESTHETIC RISKGeneral anaesthesia and local analgesia do notoccur naturally and their induction with drugs

16 PRINCIPLES AND PROCEDURESTABLE 1.1 American Society ofAnesthesiologists’ categories of anaestheticriskCategory 1 Normal healthy patient with nodetectable diseaseCategory 2 Slight or moderate systemic diseasecausing no obvious incapacityCategory 3 Mild to moderate systemic diseasecausing mild symptoms (e.g.moderatepyrexia,anaemia or hypovolaemia)Category 4 Extreme systemic disease constituting athreat to life (e.g.toxaemia,uraemia,severe hypovolaemia,cardiac failure)Category 5 Moribund or dying patientsthat even today are never completely devoid oftoxicity must constitute a threat to the life of thepatient. This can be a major or trivial threatdepending on the circumstances, but no ownermust ever be assured that anaesthesia does notconstitute a risk. When an animal owner raises thequestion of risk involved in any anaesthetic procedurethe veterinarian needs, before replying, to consider:1. The state of health of the animal. Animalspresented for anaesthesia may be fit and healthy orsuffering from disease; they may be presented forelective (‘cold’) surgery or as emergency casesneeding immediate attention for obstetrical crises,intractable haemorrhage or thoracic injuries. In theUSA the American Society of Anesthesiologists(ASA) has adopted a classification of physicalstatus into categories, an ‘E’ being added after thenumber when the case is presented as an emergency(Table 1.1).This is a useful classification but most importantlyit refers only to the physical status ofthe patient and is not necessarily a classification ofrisk because additional factors such as itsspecies, breed and temperament contribute tothe risk involved for any particular animal.Moreover, the assessment of a patient’s ‘correct’ASA classification varies between different anaesthetists(Haynes & Lawler, 1995; Wolters et al.,1996).2. The influence of the surgeon. Inexperiencedsurgeons may take much longer to perform anoperation and by rough technique produce intenseand extensive trauma to tissues, thereby causing agreater metabolic disturbance (and increased postoperativepain). Increased danger can also arisewhen the surgeon is working in the mouth orpharynx in such a way as to make the maintenanceof a clear airway difficult, or is working on structuressuch as the eye or larynx and provokingautonomic reflexes.3. The influence of available facilities. Crisesarising during anaesthesia are usually more easilyovercome in a well equipped veterinary hospitalthan under the primitive conditions which may beencountered on farms.4. The influence of the anaesthetist. The competence,experience and judgement of the anaesthetisthave a profound bearing on the degree ofrisk to which the patient is exposed. Familaritywith anaesthetic techniques leads to greater efficiencyand the art of anaesthetic administration isonly developed by experience.GENERAL CONSIDERATIONS IN THESELECTION OF THE ANAESTHETICMETHODThe first consideration will be the nature of theoperation to be performed, its magnitude, site andduration. In general, the use of local infiltrationanalgesia may suffice for simple operations suchas the incision of superficial abscesses, the excisionof small neoplasms, biopsies and the castration ofimmature animals. Nevertheless, what seems to bea simple interference may have special anaestheticrequirements. Subdermal fibrosis may make localinfiltration impossible to effect. Again, the site ofthe operation in relation to the complexity of thestructures in its vicinity may render operationunder local analgesia dangerous because of possiblemovement by the conscious animal, e.g. operationsin the vicinity of the eyes.When adopting general anaesthesia the likelyduration of the procedure to be performed willinfluence the selection of the anaesthetic. Minor,short operations may be performed quite satisfactorilyafter the intravenous injection of a small doseof an agent such as propofol or thiopental sodium.For longer operations anaesthesia may be inducedwith an ultra-short acting agent and maintainedwith an inhalation agent with or without endotrachealintubation. For most major operations under

GENERAL CONSIDERATIONS 17general anaesthesia, preanaesthetic medication(‘premedication’) will need to be considered, particularlywhen they are of long duration and theanimal must remain quiet and pain-free for severalhours after the operation. Undesirable effects ofcertain agents (e.g. ketamine) may need to becountered by the administration of ‘correcting’agents (e.g. α 2 adrenoceptor agonists, atropine).Although sedative premedication may significantlyreduce the amount of general anaesthetic whichhas to be given it may also increase the duration ofrecovery from anaesthesia. Premedication may beomitted for day-case patients when a rapid returnto full awareness is desirable.The species of animal involved is a pre-eminentconsideration in the selection of the anaestheticmethod (see later chapters). The anaesthetist willbe influenced not only by size and temperamentbut also by any anatomical or physiological featurespeculiar to a particular species or breed.Experience indicates that the larger the animal, thegreater are the difficulties and dangers associatedwith the induction and maintenance of generalanaesthesia. Methods which are safe and satisfactoryfor the dog and cat may be quite unsuitablefor horses and cattle. In vigorous and heavycreatures the mere upset of locomotor coordinationmay entail risks, as also may prolongedrecumbency.Individual animalsThe variable reaction of the different species of animals,and of individuals, to the various agentsadministered by anaesthetists will also influencethe choice of anaesthetic technique. In addition,factors causing increased susceptibility to the toxicactions of anaesthetic agents must be borne inmind. These include:1. Prolonged fasting. This, by depleting theglycogen reserves of the liver, greatly reducesits detoxicating power and when using parenterallyadministered agents in computed doses,allowance must be made for increased susceptibilityto them.2. Diseased conditions. Toxaemia causesdegenerative changes in parenchymatous organs,particularly the liver and the heart, and great caremust be taken in giving computed doses of agentsto toxaemic subjects. Quite often it is found that atoxaemic animal requires very much less than the‘normal’ dose. Toxaemia may also be associatedwith a slowing of the circulation and unless this isrecognized it may lead to gross overdosing ofintravenous anaesthetics. In those diseases associatedwith wasting there is often tachycardia and asoft, friable myocardium; animals suffering fromsuch diseases are, in consequence, liable to developcardiac failure when subjected to the stress ofanaesthesia. It is most important that the presenceof a diseased condition is detected before anaesthesiais induced.EVALUATION OF THE PATIENTBEFORE ANAESTHESIAIt is probable that most veterinary operations areperformed on normal, healthy animals. The subjectsare generally young and represent good‘anaesthetic risks’. Nevertheless, enquiry shouldbe made to ensure that they are normal andhealthy – bright, vigorous and of hearty appetite.Should there be any doubt, operations are bestdelayed until there is assurance on this point.Many a reputation has been damaged by performingsimple operations on young animals which arein the early stages of some acute infectious diseaseor which possess some congenital abnormality.When an operation is to be performed for therelief of disease, considerable care must be exercisedin assessing the factors which may influencethe choice or course of the anaesthetic. Once theseare recognized the appropriate type of anaesthesiacan be chosen and preoperative measures adoptedto diminish or, where possible, prevent complications.The commonest conditions affecting thecourse of anaesthesia are those involving the cardiovascularand respiratory systems, but the stateof the liver and kidneys cannot be ignored.The owner or attendant should always be askedwhether the animal has a cough. A soft, moistcough is associated with airway secretions thatmay give rise to respiratory obstruction and lungcollapse when the cough reflex is suppressed bygeneral anaesthesia. Severe cardiovascular diseasemay be almost unoticed by the owner and enquiry

18 PRINCIPLES AND PROCEDURESshould be made to determine whether the animalappears to suffer from respiratory distress afterexertion, or indeed appears unwilling to take exercise,since these signs may precede other signs ofcardiac and respiratory failure by many months oreven years. Dyspnoea is generally the first sign ofleft ventricular failure and a history of excessivethirst may indicate the existence of advanced renaldisease, diabetes mellitus or diabetes insipidus.The actual examination may be restricted to onewhich is informative yet will not consume toomuch time nor unduly disturb the animal. While amore complete examination may sometimes benecessary, attention should always be paid to thepulse, the position of the apex beat of the heart, thepresence of cardiac thrills, the heart sounds andthe jugular venous pressure. Examination of theurine for the presence of albumin and reducingsubstances may also be useful.Tachycardia is to be expected in all febrile andin many wasting diseases and under these circumstancesis indicative of some myocardial weakness.It can, however, also be due to nervousnessand where this is so it is often associaed withrather cold ears and/or feet. Bradycardia may bephysiological or it may indicate complete atrioventricularblock. In horses atrioventricular blockthat disappears with exercise is probably of noclinical significance. In all animals the electrocardiogrammay be the only way of determiningwhether bradycardia is physiological or is due toconduction block in the heart.The jugular venous pressure is also important.When the animal is standing and the head isheld so that the neck is at an angle of about 45°to the horizontal, distension of the jugularveins should, in normal animals, be just visible atthe base of the neck. When the distensionrises above this level, even in the absence of othersigns, it indicates an obstruction to the cranialvena cava or a rise in right atrial or ventricularpressures. The commonest cause of a rise in pressurein these chambers is probably right ventricularhypertrophy associated with chronic lung diseasealthough congenital conditions such as atrial septaldefects may also be indicated by this sign and itshould be remembered that cattle suffering fromconstrictive pericarditis, or bacterial endocarditis,may have a marked increase in venous pressure.The presence of a thrill over the heart is alwaysa sign of cardiovascular disease and suggests anincreased risk of complications arising duringanaesthesia. More detailed cardiological examinationis warranted when a cardiac thrill is detectedduring the preoperative examination.Auscultation of the heart should never be omitted,particularly when the animal’s owner is presentbecause owners expect this to be carried out,but the findings are perhaps only of limited interestto the anaesthetist. The timing of any murmursshould be ascertained by simultaneous palpationof the arterial pulse. Diastolic murmurs are alwaysindicative of heart disease and, while they may beof little importance in relation to cardiac functionduring anaesthesia, it is unwise to come to thisconclusion unless other signs, such as displacementof the apex beat, are absent. Systolic murmursmay or may not indicate the presence of heartdisease, but if other signs are absent they are mostprobably of no significance to the anaesthetist.Accurate location of the apex beat is possiblythe most important single observation in assessingthe state of the cardovascular and respiratory systems.It is displaced in most abnormal conditionsof the lungs (e.g. pleural effusion, pneumothorax,lung collapse) and in the presence of enlargementof the left ventricle. In the absence of any pulmonarydisorder a displaced apex beat indicatescardiac hypertrophy or dilatation.Oedema in cardiac failure has multiple causeswhich are not fully understood but include a failingright ventricle and an abnormal renal bloodflow that gives rise to secondary aldosteronismand excessive reabsorption of salt and water by therenal tubules. The tissue fluid appears to accumulatein different regions in different species – inhorses in the limbs and along the ventral bodywall, in cattle it is seen in the brisket region and indogs and cats the fluid tends to accumulate in theabdominal cavity. The differential diagnosis ofperipheral oedema includes renal disease, liverdisease and impaired lymphatic drainage.Pulmonary disorders provide particular hazardsfor an animal undergoing operation and anyexamination, no matter how brief, must bedesigned to disclose their presence or absence. Onauscultation attention should be directed towardsthe length of the expiratory sounds and the discov-

GENERAL CONSIDERATIONS 19ery of any rhonchi or crepitations. If rhonchi orcrepitations are heard excessive sputum is present,and the animal is either suffering from, or hasrecently suffered, a pulmonary infection.Prolongation of the the expiratory sounds, especiallywhen accompanied by high pitched rhonchi,indicate narrowing of the airways or bronchospasm.Respiratory sounds may be absent inanimals with pneumothorax, extensive lung consolidation,or severe emphysema; they are usuallyfaint in moribund animals.Uneven movements between the two sides ofthe chest is a reliable sign of pulmonary diseaseand one which is easily and quickly observed. Theanimal should be positioned squarely while theexaminer stands directly in front of it and thendirectly behind it. In small animals uneven movementof the two sides of the chest is often betterappreciated by palpation rather than by inspection.The mouth should be examined for the presenceof loose teeth which might become dislodgedduring general anaesthesia and enter the tracheobronchialtree. Other mucous membranes shouldbe inspected for evidence of anaemia, denoted bypaleness.Biochemical tests prior to anaesthesiaThe question as to whether preanaesthetic urineand blood analysis should be performed routinelybefore every elective anaesthetic is controversial.Such tests are essential to confirm or excludedisease conditions suspected as a result of clinicalhistory and examination, but the cost/benefit oftheir use in animals which appear perfectlyhealthy can be argued on the basis that the resultsrarely would alter the anaesthetic protocol to beemployed. Urine testing is simple, inexpensiveand is particularly important in dogs for in theseanimals renal disease and previously undiagnoseddiabetes mellitus are common. Urine samples maybe less readily obtainable from other species of animal.The Association of Veterinary Anaesthetistsdebated (Spring Meeting, 1998) the question as tothe need for routine preanaesthetic checks onhaematological and biochemical profiles, andvoted that they were unnecessary if the clinicalexamination was adequate. Although in a veryoccasional case (e.g. the detection of a partialhepto-portal shunt in a young dog) such tests maydetect an unsuspected disease state, in the vastmajority of apparently fit healthy animals theyconstitute an unnecessary expense, and indeed theextra cost involved may prevent an owner fromagreeing to continuation of treatment necessaryfor the wellbeing of the patient.Provided a brief examination such as thatdescribed is carried out thoroughly, and that theexaminer has sufficient skill and experience to recognizethe significance or lack of significance ofthe findings, most of the conditions that have abearing on the wellbeing of an animal in the perioperativeperiod will be brought to light so thatappropriate measures can be taken to protect itfrom harm.SIGNIFICANCE OF CONDITIONSFOUND BY PREANAESTHETICEXAMINATIONCARDIOVASCULAR AND RESPIRATORYDISEASEThe cardiovascular and respiratory systems arethose which govern the rate at which oxygen canbe made available to the tissues of the body. Manyyears ago Nunn and Freeman drew attention tothe crucial fact that this rate is equal to the productof the cardiac output and the oxygen content of thearterial blood. Since the arterial oxygen contentapproximates to the product of the oxygen saturationand the quantity of oxygen which can be carriedby the haemoglobin (about 1.34 ml per g ofhaemoglobin when fully saturated), the oxygenmade available to the body can be expressed by asimple equation:Available oxygen = cardiac output (ml/min)(ml/min) × arterial saturation (%)× haemoglobin (g/ml)× 1.34This equation, of course, makes no allowance forthe small quantity of oxygen which is carried inphysical solution in the plasma, but it serves toillustrate the way in which three variables combineto produce an effect which is often greaterthan is commonly supposed. If any one of the three

20 PRINCIPLES AND PROCEDURESdetermining variables on the right-hand side ofthe equation is changed, the rate at which oxygenis made available to the tissues of the body isaltered proportionately. Thus, if the cardiac outputis halved, the available oxygen is also halved. Iftwo determinants are lowered simultaneouslywhile the third remains constant, the effect on theavailable oxygen is the product of the individualchanges. For example, if the cardiac output and thehaemoglobin concentration are both halved whilethe arterial oxygen saturation remains at about thenormal 95%, only one-quarter of the normalamount of oxygen is made available to the bodytissues. If all three variables are reduced the effectis, of course, even more dramatic.DRUG METABOLISM AND DISEASE STATESInducers(e.g. phenobarbitone)Direct effect onthe enzyme(e.g. propofol)Lack of co-factors(e.g. oxygen)EnzymeInhibitorsEnvironmentalchanges(e.g. hypoxia,inflammation)Substratecompetition(e.g. midazolam)FIG.1.6 Factors which may change enzyme function.Drugs are usually metabolized through severalpathways so that they are changed from fat soluble,active, unexcretable drugs into water soluble,inactive drugs that are able to be excreted by thekidneys and in the bile. Since the mammalian bodymetabolizes many thousands of compounds everyday and has far fewer enzymes, each enzymemetabolizes many substrates. Only very rarely,if ever, will one enzyme metabolize only onesubstrate. Many things change enzyme function.Mechanisms for enzyme induction are poorlyunderstood, unlike inhibition, which has beenmuch more extensively studied. Enzyme inductionis a slow process involving an increased amount ofenzyme in the cell over about 24 to 48 hours,whereas inhibition is quick and sometimes occursafter only one dose of an inhibitor. Since enzymesare proteins their concentrations inside cells maybe changed by a variety of factors (Fig. 1.6).There is now an increasing amount of informationabout how enzymes change in response to onestressful stimulus but it is important to recognizethat usually several stimuli exist at the same timein each critically ill animal. Most chemical reactionsare sensitive to temperature, speeding up asthe temperature increases and slowing with adecrease in temperature, but in spite of thisall fevers do not increase the rate of metabolismof drugs: the cause of the fever is important.Infections and pyrogens cause the release ofinflammatory mediators which reduce the expressionand activity of many enzymes. Non-traumaticstress has been shown to reduce enzyme function,possibly by decreased hepatic blood flow resultingin hypoxaemic induced reduction in metabolizingenzymes. Endogenous corticosteroid secretion aspart of the stress response or exogenous steroidgiven to treat disease will change the expression ofdrug metabolizing enymes, and metabolic activityalso varies with age. The anaesthetist must beaware of these factors so that any increase ordecrease in the duration of drug action may beanticipated.FACTORS AFFECTING TRANSPORT OFDRUGS IN THE BODYMost drugs are carried in the bloodstream partlybound, usually by electrostatic bonds, to the proteinsof the plasma, albumin being far the mostimportant for the majority of agents. Light or moderateprotein binding has relatively little effect ondrug pharmacokinetics or pharmacodynamics.Heavy protein binding with drugs such asthiopental results in a low free plasma concentrationof the drug, which may become progressively

GENERAL CONSIDERATIONS 21augmented as the available binding sites becomesaturated. The bound drug is, of course, in dynamicequilibrium with free (active) drug in the plasmawater. The bonds are generally reversible and conformto the law of mass action:[D]drug+[P]proteinThe association and dissociation processes takeplace very quickly, and can generally be taken tobe instantaneous. The equilibrium association constantK A is defined as the ratio of rate constants,and of bound to the product of unbound concentrations:k fbk bf[DP]complexdrugs by lowering the free plasma concentration,thereby increasing the concentration gradient fordiffusion from the gut lumen. An apparent exceptionto the increased activity of drugs in hypoproteinaemicanimals is the resistance to tubocurarineseen in cases of liver disease. This is explained bythe fact that tubocurarine binds to γ globulin ratherthan albumin and reversed albumin/globulinratios are common in hepatic diseases.Not surprisingly, for a protein with a molecularweight of about 65 000, there are several geneticallyacquired variants of albumin. Furthermore,the configuration of the albumin molecule alsochanges during illness and, for example, in renalfailure. These changes can be demonstrated byelectrophoresis but their significance for the bindingof drugs in vivo is not known.This simple relationship is often obscured by thefact that one protein molecule may possess severalbinding sites for any particular drug, which mayor may not have the same association constant. Itcan generally be assumed, however, that so long asthe plasma proteins remain unchanged, the ratioof ‘free’ to ‘bound’ drug will remain constant. Thisratio depends on the nature of the drug molecule.Small, neutral, water soluble drugs will not bind toprotein at all but larger lipophilic molecules mayexhibit very high binding ratios.Anaemia is often associated with hypoproteinaemiaand this can have marked effects inanaesthesia. In conditions where there is anaemiaand hypoalbuminaemia, a greater fraction of agiven dose of a drug will be unbound and this willbe even greater if other bound drugs have alreadyoccupied many of the binding sites.This can resultin an increased peak activity of the drug. Liver diseasegiving rise to hypoalbuminaemia can result inreduced binding of drugs such as morphine so thatsmaller than normal doses of this analgesic will beeffective when pain relief is needed. A rapid intravenousinjection of an albumin-bound drug mayalso lead to increased pharmacological activitybecause the binding capacity of the albumin in thelimited volume of blood with which the drug initiallymixes is exceeded and more free (active)drug is presented to the receptor sites. Plasma proteinbinding enhances alimentary absorption ofRENAL DISEASEChronic renal disease is common in dogs, andaffected animals cannot produce concentratedurine. Dehydration from any cause deprives thekidneys of sufficient water for excretory purposes(Fig. 1.7). To ensure that these animals receive anadequate fluid intake over the anaesthetic period itis usually necessary to administer fluid by intravenousinfusion. A uraemic circle can also be setup in animals suffering from chronic renal diseaseif the arterial blood pressure is allowed to decreasebecause of anaesthetic overdose or haemorrhageand renal ischaemia ensues (Fig. 1.8). The maintenanceof the circulating fluid volume is mostimportant in all animals with chronic renal diseaseand it is important that adequate venous access isassured before anaesthesia and operation.Acute renal failure can be defined as an abruptdecline in renal function with a decrease inglomerular filtration rate (GFR) resulting in theretention of nitrogenous waste products. Acuterenal failure is classified into:(i) Prerenal failure, denoting a disorder in thesystemic circulation that causes renal hypoperfusion.Implicit here is that correction of the underlyingcirculatory disturbance (e.g. by improvementin cardiac function or repletion of volume) restoresthe GFR. However, prerenal failure is often followedby transition to:

22 PRINCIPLES AND PROCEDURESAbnormal high water lossInadequate water intakeChronic renal diseaseVomiting, diarrhoeaOliguriaDilute urineDeathUraemiaOliguria and dilute urineFIG.1.7 Effect of water deprivation in dogs suffering from chronic renal disease.(ii) Intrinsic renal failure, where correction ofthe underlying circulatory impairment does notrestore the GFR to normal levels. Intrinsic renalfailure generally includes tubular necrosis or theblocking of tubules by cell debris or precipitatedproteins and there is no question of unaffectednephrons compensating for failing nephrons asthere is in chronic renal failure. Instead all areinvolved in a massive disturbance of renal functionwith diversion of blood flow away from therenal cortex towards the medulla and an overallreduction in renal perfusion. There is, however, apotential for complete recovery, whereas chronicrenal failure invariably progresses over a variableperiod of time with no hope of recovery of renalfunction.(iii) Postrenal failure (obstructive) is a third possibility.Excessive reliance on blood pressure maintenanceto between the ‘autoregulatory range’ by infusionor the use of vasoactive drugs overlooks the factthat renal blood flow is labile since the kidneyscontribute to the regulation of blood pressure. Theincidence of acute renal failure is high after the useof intravenous contrast radiological media, nephrotoxicdrugs (e.g. non-steroidal anti-inflammatorydrugs, gentamycin, amphotericin). The use ofdopamine as a renoprotective agent is controversial;it is said to act as a renal vasodilator but it isprobable that the increased renal blood flow whenit is given in doses of 2–5 µg/kg/min is due toinotropic effects because other non-dopaminergicinotropic agents have similar effects on renal bloodflow.PREPARATION OF THE PATIENTCertain operations are performed as emergencieswhen it is imperative that there shall be no delayand but little preparation of the patient is possible.Amongst these operations are repair of thoracicinjuries, the control of severe, persistent haemorrhage,and certain obstetrical interferenceswhere the delivery of a live, healthy neonate isof paramount importance. For all other operations,time and care spent in preoperative preparationare well worthwhile since proper preparationnot only improves the patient’s chances ofsurvival, but also prevents the complicationswhich might otherwise occur during andafter operation. When operations are to beperformed on normal, healthy animals, onlythe minimum of preparation is required beforethe administration of a general anaesthetic, butoperations on dehydrated, anaemic, hypovolaemicor toxic patients should only be undertakenafter careful preoperative assessement andpreparation.FOOD AND WATERFood should be withheld from the animal on theday it is to undergo an elective operation undergeneral anaesthesia. A distended stomach may

GENERAL CONSIDERATIONS 23DehydrationDrug overdoseHaemorrhagewithholding water for about six hours beforeabdominal operations because this appears toresult in slowing of fermentation in the rumen.FLUID AND ELECTROLYTESArterial hypotensionRenal ischaemiaOliguriaUraemiaDeathImpairedrenal functionFIG.1.8 Effect of drug overdose or haemorrhage onarterial blood pressure leading to renal failure and death inthe presence of chronic renal disease.interfere with the free movement of the diaphragmand hinder breathing. In dogs, cats and pigs, a fullstomach predisposes to vomiting under anaesthesia.In horses a full stomach may rupture when thehorse falls to the ground as unconsciousness isinduced. In ruminants, a few hours of starvationwill not result in an appreciable reduction in thevolume of the fluid content of the rumen but itseems to reduce the rate of fermentation withinthis organ, thus delaying the development of tympanywhen eructation is supressed by generalanaesthesia.Excessive fasting exposes the patient to risksalmost as great as those associated with lack ofpreparation and should not be adopted. Any fastingof birds and small mammals is actually lifethreatening.Many clinicians are of the opinionthat prolonged fasting in horses predisposes topostanaesthetic colic by encouraging gut stasis. Innon-ruminants, free access to water should beallowed right up to the time premedication isgiven, but in ruminants there is some advantage inThe water and electrolyte balance of an animal is amost important factor in determining uncomplicatedrecovery or otherwise after operation. Therepair of existing deficits of body fluid, or of one ofits components, is complex because of the interrelationsbetween the different electrolytes andthe difficulties imposed by the effects of severesodium depletion on the circulation and renalfunction.Fortunately, the majority of animal patients sufferonly minor and recent upsets of fluid balance sothat infusion with isotonic saline, Hartmann’s solutionor 5% dextrose, depending on whether sodiumdepletion or water depletion is the more predominant,is all that is required. An anaesthetic shouldnot be administered to an animal which has adepleted circulating blood volume for the vasodilatationcaused by anaesthetic agents may lead toacute circulatory failure, and every effort should bemade to repair this deficit by the infusion of blood,plasma or plasma substitute before anaesthesia isinduced. In many instances, anaesthesia and operationmay be safely postponed until the total fluiddeficit is made good and an adequate renal outputis achieved, but in cases of intestinal obstructionoperation should be carried out as soon as theblood volume has been restored. Attempts torestore the complete extracellular deficit before theintestinal obstruction is relieved result in furtherloss of fluid into the lumen of the obstructed boweland, especially in horses, make subsequent operationmore difficult. When in doubt about thenature and volume of fluid to be administered, it isas well to remember that, with the exception oftoxic conditions and where severe hypotensiondue to hypovolaemia is present, an animal’s conditionshould not deteriorate further if sufficientfluid is given to cover current losses. These currentlosses include the inevitable loss of water throughthe skin and respiratory tract (approximately20–60 ml/kg/day depending on the age andspecies of the animal), the urinary and faecal loss,and any abnormal loss such as vomit.

24 PRINCIPLES AND PROCEDURESHAEMOGLOBIN LEVELAs already mentioned on page 21 anaemia may betreated to raise the haemoglobin concentration tomore reasonable value before any major premeditatedsurgery is performed. When operation can bedelayed for two or more weeks, the oral or parenteraladministration of iron may increase thehaemoglobin to an acceptable value, (eg. 10 to12 g/100 ml blood depending on the species of animal)but when such a delay is inadvisable eitherthe transfusion of red blood cells is indicated orlow levels of haemoglobin must be tolerated fortheir effect of decreasing blood viscosity.DIABETES MELLITUSIt is sometimes necessary to anaesthetize a dog orcat suffering from diabetes mellitis and if the conditionis already under control no serious problemsare likely to be encountered. However, if thenormal dose of insulin is given, starvation beforeoperation and inappetance afterwards may giverise to hypolgycaemia. There are over 30 commerciallyavailable preparations of insulin and theyhave different durations of action. Short actinginsulins (e.g. soluble insulin) have a peak effect at2 to 4 hours and their effects last for 8 to 12 hours.Medium acting insulins (e.g. semilente) have apeak effect at 6 to 10 hours and activity for up to24 hours. Long acting insulins have a peak effect at12 to 15 hours and one dose lasts for at least36 hours. For this reason it is advisable to switch topurely short acting insulin a few days prior to electivesurgery. By doing this, there is effectively noactive long acting insulin preparation left on theday of operation and it becomes much easier tocontrol the blood sugar around the perioperativeperiod.If an emergency operation has to be performedon an uncontrolled diabetic then the condition ofthe animal requires careful assessment and treatment.Ketonuria is an indication for treatmentwith gluose and soluble insulin, whilst overbreathingis a sign of severe metabolic acidosis.This must be treated with the infusion of sodiumbicarbonate solution but the amount of bicarbonateneeded in any particular case can only becalculated with any degree of certainty when theacid–base status is known from laboratory examinationof an anaerobically drawn arterial bloodsample. In the absence of this data the animal maybe treated by infusing 2.5% sodium bicarbonatesolution until the overbreathing ceases. Because ofthe presence of an osmotic diuresis, many uncontrolleddiabetics also require treatment for dehydration.The object of management is not to try tocorrect all disturbances as quickly as possible, soas achieving in an hour or two what normallyshould take 2 to 3 days. Doing this may produceswings in plasma osmolarity that can be responsiblefor the development of cerebral oedema. Allthat is necessary prior to emergency surgery is tocorrect any hypovolaemia and ensure that theblood glucose level is declining.INFLUENCE OF PRE-EXISTING DRUGTHERAPYModern therapeutic agents are often of considerablepharmacological potency and animals presentedfor anaesthesia may have been exposed toone or more of these. Some may have been givenas part of the preoperative management of the animalbut whatever the reason for their administrationthey may modify the animal’s response toanaesthetic agents, to surgery and to drugs givenbefore, during and after operation. In some casesdrug interactions are predictable and these mayform the basis of many of the combinations used inmodern anaesthesia, but effects which are unexpectedmay be dangerous.In an ideal situation a drug action would occuronly at a desired site to produce the sought-aftereffect. In practice, drugs are much less selective andare prone to produce ‘side effects’ which have to beanticipated and taken into account whenever thedrug is administered. (A ‘side effect’ may bedefined as a response not required clinically, butwhich occurs when when a drug is used within itstherapeutic range.) Apart from these unavoidableside effects which are inherent, adverse reactions todrugs may occur in many different ways which areof importance to the anaesthetist. These include:1. Overdosage. For some drugs exact dosing maybe difficult. Overdosage may be absolute as whenan amount greater than the intended dose is given

GENERAL CONSIDERATIONS 25in error, or a drug is given by an inappropriateroute, e.g. a normal intramuscular dose may constitutea serious overdose if given intravenously.Relative overdose may be due to an abnormality ofthe animal; an abnormal sensitivity to digitalis isfound in hypokalaemic animals and newborn animalsare sensitive to non-depolarizing neuromuscularblocking drugs. The use in dogs and cats offlea collars containing organophosphorus compoundsmay reduce the plasma cholinesterase andprolong the action of a normal dose of suxamethonium.Overdose manifestations vary from acute tochronic and may produce toxicity by a quantitativelyenhanced action which can be an extensionof the therapeutic action, e.g. neostigmine inexcess for the antagonism of non-depolarizingneuromuscular block. They may also be due toside effects (e.g. morphine producing respiratorydepression).2. Idiosyncrasy. Some animals may have agenetically determined response to a drug whichis qualitatively different to that of normal individuals,as in the porcine hyperpyrexia syndrome(porcine malignant hyperthermia).3. Intolerance. This is exhibiting a qualitativelynormal response but to an abnormally low or highdose. It is usually simply explained by theGaussian distribution of variation in the animalpopulation.4. Allergy. Allergic responses are, in general, notdose related and the allergy may be due to thedrug itself or to the vehicle in which it is presented.Thereaction may take a number of forms:shock, asthma or bronchospasm, hepatic congestionfrom hepatic vein constriction, blood disorders,rashes or pyrexia. Terms such as ‘allergic’,‘anaphylactic’, ‘anaphylactoid’ or ‘hypersensitive’have specific meanings to immunologists but,unfortunately, they are often used interchangeably.Strictly speaking it is inaccurate to use any ofthese terms until evidence of the immunologicalbasis of a reaction has been established. Manyof these reactions are histamine-related butother mediators such as prostaglandins, leucotrienesor kinins may be involved. Some immunologistsconsider that where either themediator or the mechanism involved is uncertain,reactions are best described as ‘histaminoid’ or‘anaphylactoid’.5. Drug interactions. Despite the importanceof drug interactions there is little information inthe veterinary literature on this subject. Drug interactioncan occur outside the body, as when twodrugs are mixed in a a syringe before they areadministered, or inside the body after administrationby the same or different routes. It is generallyunwise to mix products or vehicles in the samesyringe or to administer a drug into an intravenousinfusion of another drug for this may result inprecipitation of one or both drugs or even the formationof new potentially toxic or inactive compounds.The result of the interaction between twodrugs inside the body may be an increased ordecreased action of one or both or even an effect completelydifferent from the normal action of eitherdrug. The result of interaction may be simply thethe sum of the actions of the two drugs (1 + 1 = 2),or greater (1 + 1 > 2), when it is known as synergism.When one agent has no appreciable effect butenhances the response to the other (0 + 1 > 1) theterm ‘potentiation’ is used to describe the effect ofthe first on the action of the second. An agent mayalso antagonize the effects of another and theantagonism may be ‘chemical’ if they form an inactivecomplex, ‘physiological’ if they have directlyopposing actions although at different sites, or‘competitive’ if they compete for the same receptors.Non-competitive antgonism may result frommodification by one drug of the transport, biotransformationor excretion of the other. In the liverthe non-specific metabolic degradation of manydrugs occurs and many different agents have theability to cause an ‘enzyme induction’ whilst a fewdecrease the activity – ‘enzyme inhibition’. Analgesicssuch as phenylbutazone cause enzymeinduction and can produce a great increase in therate of metabolism of substrates. Barbiturate treatmentof epilepsy may almost halve the half-life ofdexamethasone with a conseqent marked deteriorationin the therapeutic effect of this steroidal substance.Competition for binding sites and thedisplacement of one drug from the bound (inactive)form may lead to increased toxicity. For example,warfarin (which is sometimes used in themanagement of navicular disease in horses) is displacedby several agents, including the analgesicphenylbutazone, with a resulting risk of haemorrhage.

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Patient monitoring and clinical2measurementINTRODUCTIONFrom the earliest days of anaesthesia the anaesthetisthas monitored the patient’s pulse rate, pattern ofbreathing and general condition. Advances in electronictechnology have made reasonably reliable,easily attached, non-invasive monitoring devicesavailable for clinical practice. Observations andmeasurements of certain parameters before, during,and after anaesthesia provide important datato support the clinical assessment of the animal’scondition and improve the chances of survival ofthe very ill by indicating what treatment is needed,as well as the response to treatment already given.It is necessary to know what to measure as well ashow to measure it and not all anaesthetists may agreeon the priority ranking of the monitoring devicesavailable. There can be little doubt that to introducethe full panoply of monitoring equipment for shortbloodless procedures on healthy animals may turna simple anaesthetic administration into a complexone with unnecessary distractions. However, formajor surgery, for anaesthesia and surgery ofpoor-risk patients, and for equine anaesthesia, itwould be difficult to defend the failure to use monitoringequipment, especially if it were available.GENERAL CONSIDERATIONSRELATING TO MONITORINGAnaesthetic mishaps may be caused by mechanicalmalfunction, disconnection of equipment, orhuman error. Judgmental error frequently occurswhen the anaesthetist is in a hurry and circumventsbasic practices and procedures, or when adecision must be made in an emergency. Theprevalence of complications may also be associatedwith inadequate training or experience ofthe anaesthetist. Knowledge and experience are afunction of the nature of the training received andthe years of practice, but proper vigilance at alltimes can only be generated by self-motivation.Routines should be developed to ensure thateach aspect of apparatus function is checkedbefore use. Failure to follow a simple check list inevery case features high on the list of causes ofanaesthetic disasters. All anaesthetic equipment,including monitoring devices, should be maintainedin good functioning order. It should be amatter of course to maintain monitors with a batteryback-up fully charged in case of need in anarea without a convenient electricity outlet nearby,failure of electricity supply, or the need to disconnectfrom the main supply to minimize electricalinterference with other monitoring equipment.Proficiency with methods of electronic surveillancemust be acquired during minor proceduresso that they can be applied properly in circumstanceswhere their use is mandatory (e.g.during major surgery or a cardiovascular crisis).Routine use ensures that probes, sensors, electrodes,etc. can be applied quickly to the animaland increases the likelihood that the informationobtained is reliable.29

30 PRINCIPLES AND PROCEDURESAlthough current practice is to establish monitoringonly after the animal has been anaesthetized,it must be recognised that many complicationsoccur during induction of anaesthesia. Ideally,especially for poor-risk patients, monitoringshould begin when the drugs for premedicationare administered. Dogs and cats may vomit afteradministration of an opioid and the quantity andcontent of the vomit may warn that the animal wasfed recently and so may be at risk for regurgitationand pulmonary aspiration of gastric material.Brachycephalic breeds and animals with respiratoryproblems should always be observed afteradministration of preanaesthetic drugs becausesedation may cause partial or complete airwayobstruction or serious respiratory depression. InAbbreviationsTIMEAG 1 2 3 4 AE0 15 30 45 0 15 30 45 0 15 30O 2 flow L/minEnd tidal CO 2Vaporizer %2237 32 38 38 381.75 21.5HR180Arterial pressure:160V V SystolicDiastolic140X Mean120Ventilation:Spontaneous 100S80ControlledC6040AI Anes. inductionAG Begin inhalant20AE End anes.SS Surgery start 10SE Surgery endE Extubation 0Temperature 103.1Fluids (ml) LRSOtherVVV VVVV VVS101.6 101.6175 350180160140V VV V 120VV VV V V VV V V VVVVVVVV VXXVXX X X X X X XX X X V VVVV 100VVX XXX X X X 80XXX VVV VVVVV V VV VVV 60V VV VVVV40SS2010099.9 98.8 98.6 98.1550 850 1050 143097.5 97.2 96.6 96.12050 2200 2530 265096.52725DETAILED COMMENTS:1. Oxymorphone 1.5mg IV2. Move to O.R. 1200mg Cefotetan IV3. Change from indirect to direct arterial BP monitoring4. Morphine 30mg IMFig.2.1 Anaesthetic record of a 61 kg,6-year-old female Great Dane anaesthetized for exploratory laparotomy becauseof torsion of the spleen. Anaesthesia was induced by intravenous administration of ketamine,200 mg,and diazepam,10mg,and maintained with isoflurane.Heart rate,blood pressure and respiratory rate were recorded at regular intervals tofacilitate early recognition of adverse trends.

PATIENT MONITORING AND CLINICAL MEASUREMENT 31any animal, evaluation of the degree of sedationproduced by premedicant drugs may indicate thatthe anaesthetic plan should be reassessed and eitherdrug doses reduced or additional agents included.Careful observation of the patient duringinduction of anaesthesia may allow precise titrationof drugs to achieve the desired depth of anaesthesiaand ensure early recognition of acomplication that requires immediate specifictreatment, such as cyanosis, anaphylaxis, or cardiacarrest. Where possible, patients at risk forcomplications may be attached to specific monitoringequipment before induction of anaesthesia.Appropriate equipment for this would be the electrocardiograph(ECG) and a device for measurementof blood pressure.Recording drugs, dosages and responses foreach patient is essential and provides valuableinformation for any subsequent time that anaesthesiamay be needed. Noting all measurements on ananaesthetic record provides a pictorial descriptionof changes that can be used to predict complicationsand plan treatment (Fig. 2.1). Retrospectiveevaluation of difficult cases and of series of records,perhaps of patients with similar surgical procedures,or to compare different anaesthetic protocols,can be used to monitor the anaesthetist’s performanceand identify difficult situations that requirefurther thought and improved management. Forresearch purposes, data can be acquired into acomputer for accurate data summaries.Monitoring animals during anaesthesia mustinclude observation of behaviour and reflexes andmeasurement of various physiological parametersat regular intervals to accomplish two objectives.The first objective is to ensure that the animal survivesanaesthesia and surgery. The second objectiveis to obtain information that can be used toadjust anaesthetic administration and managementto minimize physiological abnormalities,which is especially important for animals thathave already compromized organ systems. Thegoal is to prevent development of preventableadverse consequences 1 hour, 12 hours, or even3 days after anaesthesia.Monitoring should continue into the recoveryperiod to determine the need for additional analgesicdrugs and to record serious deviations inbody temperature. Mucous membrane colourshould be checked for at least 20minutes after theanimal has been disconnected from oxygen as itmay take that long for hypoxaemia to develop inanimals that are moderately hypoventilating andbreathing air.A variety of methods using inexpensive orexpensive equipment can be used to monitor parametersdetermined by the species of animal to beanaesthetized and by the abnormalities alreadypresent in the patient. Not all monitoring techniquesneed to be applied to every patient. A recommendationfor three levels of monitoring is presentedin Table 2.1; level 1 monitoring information shouldbe obtained from all anaesthetized animals, level 2monitors are affordable and recommended forroutine use in some groups of patients, and level 3monitors individually offer improved monitoringfor patients with specific problems.This chapter will describe the techniques ofmonitoring using a systems approach, and offerguidelines for interpretation of the informationobtained. Further recommendations are given inthe chapters devoted to species anaesthesia andthe chapter on management of complications.CLINICAL ASSESSMENT OF THEPATIENTMONITORING THE CENTRAL NERVOUSSYSTEMAn early attempt at defining depth of anaesthesiathrough observation of changes in reflexes, muscletone, and respiration with administration ofincreased concentration of ether resulted in classificationof anaesthesia into four stages (Fig. 2.2).The animal was said to make the transition fromconsciousness to deep anaesthesia by passingsequentially through Stage I (in which voluntaryexcitement might be observed), Stage II (when theanimal appeared to be unconscious but exhibitedinvoluntary muscle movement, such as limbpaddling, and vocalization), Stage III (surgicalanaesthesia), and Stage IV (anaesthetic overdoseimmediately prior to death). Stage III was furtherdivided into Plane 1 (light anaesthesia sufficientonly for non-painful procedures), Plane 2(medium depth anaesthesia employed for most

32 PRINCIPLES AND PROCEDURESTABLE 2.1 Prioritization of monitoringMonitor Information obtained Specific useLevel 1 (Basic monitoring)● Palpebral and pedal reflexes,eye position Depth of anaesthesia All anaesthetized animals● Respiratory rate and depth of chest or Adequacy of ventilation All anaesthetized animalsbag excursion● Oral mucous membrane colour Oxygenation All anaesthetized animals● Heart rate,pulse strength,capillary refill Assessment of circulation All anaesthetized animalstime● Temperature Temperature Dogs and cats anaesthesiagreater than 30 min;all inhalationanaesthesiaLevel 2 (Routine use recommended for some patients)● Arterial blood pressure measurement Blood pressure All inhalation anaesthesia;(indirect or direct methods)cardiovascular disease ordepression● Blood glucose Blood glucose Paediatric patients;diabetics;septicaemia;insulinoma● Electrocardiography Cardiac rate and rhythm;diagnosis All inhalation anaesthesia;of arrhythmia or cardiac arrest thoracic trauma or cardiacdisease● Pulse oximetry Haemoglobin oxygen saturation; Small animals breathing airpulse rateduring anaesthesia;thoracictrauma or pulmonarydisease;septicaemia/endotoxaemia● Urine output,either by expression Urine volume produced during Renal disease;some urinary tractof urinary bladder or by urethral anaesthesia;indirect assessment surgery;multiorgan failurecatheterizationof adequacy of tissue perfusionLevel 3 (Use for specific patients or problems)● Anaesthetic gas analyser Inspired and end-tidal anaesthetic Any patient on inhalationagent concentration;evaluation of anaesthetic agentdepth of inhalation anaesthesia● Blood gases and pH PaCO 2 ,PaO 2 ,pH,HCO 3 ;base Suspected hypoventilation orexcess/deficithypoxaemia;measurement ofmetabolic status● Capnography End-tidal carbon dioxide Suspected hypoventilationconcentration;estimate ofduring inhalation anaesthesia;adequacy of ventilation;warning patients at risk for complicationsof circuit disconnect or cardiacarrest● Cardiac output measurement Cardiac output Multiorgan failure;researchinvestigations● Central venous pressure Adequacy of blood volume Dehydrated small animalpatients;portosystemic shunt● Electrophysiological diagnostics Cerebral ischaemia;assessment of Reliability is being investigated(electroencephalogram,cortical evoked depth of anaesthesiaresponses,spectral edge frequency)● Packed cell volume and total protein Haemodilution and protein Haemorrhage;large volumeconcentrationinfusion of crystalloidsolution● Peripheral nerve stimulator Neuromuscular transmission Use of neuromuscular blockingagents

PATIENT MONITORING AND CLINICAL MEASUREMENT 33surgical procedures), Plane 3 (deep anaesthesia),and Plane 4 (excessively deep anaesthesia). Althoughthe progression of changes described inFig. 2.2 are generally accurate representations ofthe transition from light to deep ether anaesthesia,the rate of changes vary for the newer inhalationagents and are altered by concurrent administrationof injectable drugs.Eye position and reflexesEye movements are similar with thiopental,propofol, halothane, and isoflurane in that theeyeball rotates rostroventrally during light andmoderate depths of surgical anaesthesia, returningto a central position during deep anaesthesia (Fig.2.3). Muscle tone is retained during ketamineanaesthesia and the eye remains centrally placedin the orbit in dogs and cats (Fig. 2.4), and onlyslightly rotated in horses and ruminants. Finenystagmus may be present in horses anaesthetisedwith ketamine (See Chapter 11). The palpebralreflex, which is partial or complete closure ofthe eyelids (a blink) elicited by a gentle tap atthe lateral canthus of the eye or gentle stroking ofthe eyelashes, is frequently a useful guide to depthof anaesthesia. At a plane of anaesthesia satisfactoryfor surgery, the palpebral reflex is weak andnystagmus is absent. A brisk palpebral reflexdevelops when anaesthesia lightens. Ketamineanaesthesia is associated with a brisk palpebralreflex.A corneal reflex is a similar lid response elicitedby gentle pressure on the cornea. The presence of acorneal reflex is no indicator of depth of anaesthesiaand may still be present for a short time aftercardiac arrest has occurred.The pedal reflex is frequently tested in dogs,cats and small laboratory animals to determine ifdepth of anaesthesia is adequate for the start ofVENTILATIONPatternPupilEyeballpositionEyereflexesIntercostalDiaphragmLacrimationResponse tosurgical stim.AwakeStage IIStage IIILIGHTPlane 1MEDIUMPlane 2IrregularpantingIrregularbreathholdingRegularRegularshallowPalpebralDEEPPlane 3JerkyCornealStage IVFIG.2.2 Changes in ventilation and eye signs follow recognized patterns with different stages of inhalation anaesthesia.The progression of these changes will be influenced by inclusion of injectable anaesthetic agents (adapted from Soma,1971).

34 PRINCIPLES AND PROCEDURESof pentobarbital to facilitate rapid transitionthrough any excitement stage, small incrementsare administered over several minutes just untilthe whisker reflex is abolished.MONITORING OF RESPIRATORY RATE ANDCARDIOVASCULAR FUNCTIONFIG.2.3 The rostroventral rotation of the eye in this dogis consistent with light and medium planes of halothane orisoflurane anaesthesia.surgery. Pinching the web between the toes or firmpressure applied to a nail bed will be followedby withdrawal of the limb if anaesthesia isinadequate.The whisker reflex in cats, where pinching ofthe pinna elicits a twitch of the whiskers, has beenused to assist in titration of pentobarbital to anadequate depth of anaesthesia. After administrationof one-third to one-half of the calculated doseMeasurements of respiratory rates, heart rates,and blood pressure are not reliable guides to depthof anaesthesia, although increasing the depth ofanaesthesia by increasing administration of ananaesthetic agent produces increased respiratoryand cardiovascular depression. It is not uncommonfor an unstimulated dog anaesthetisedwith an inhalation agent to have a low arterialblood pressure and yet in the next minute startmoving its legs and chewing on the endotrachealtube in response to a skin incision, all accompaniedby a dramatic increase in blood pressure.Inhalation agents may elicit different responses,for example, increasing depth of isoflurane anaesthesiamay decrease respiratory rates whereasincreasing depth of halothane anaesthesia mayresult in increased respiratory rates. Furthermore,today in a clinical patient, more than one anaestheticor preanaesthetic agent is generally usedand the cardiopulmonary effects are determinedby the combination of agents used and the doserates.FIG.2.4 The central position of the eye,with a brisk palpebral reflex,is observed typically during ketamine anaesthesia incats.

PATIENT MONITORING AND CLINICAL MEASUREMENT 35FIG.2.5 This gas analyser (Capnomac Ultima TM ,Datex-Engstrom Inc.,Tewksbury,Maryland,USA) is monitoring a 27 kgfemale English Bulldog that was premedicated with glycopyrrolate and butorphanol and anaesthesia induced with propofol.She has been breathing oxygen and isoflurane at a vaporizer setting of 2.5% for 5 minutes.The monitor indicates that theinspired (Fi) isoflurane concentration is less than the vaporizer setting and that the end-tidal (ET) isoflurane concentrationis less than MAC value.Anaesthetic gas analysersThe anaesthetic gas analyser measures the concentrationof inhalation anaesthetic agent in inspiredand expired gases (Fig. 2.5). The gases are sampledat the junction of the endotracheal tube andbreathing circuit either directly in-line or by continuousaspiration of gases at a rate of 150 ml/minto a monitor placed at some distance from thepatient. To assess the depth of anaesthesia, theend-tidal concentration of inhalation agent ismeasured (alveolar concentration is measured atthe end of exhalation) and compared with theMAC value for that inhalant anaesthetic andspecies (Table 2.2). Higher than MAC values willbe required to prevent movement in response tosurgery, usually 1.2 to 1.5 times MAC, when anaesthesiais maintained almost entirely by inhalationagent. Less than MAC value may be sufficientwhen analgesia is provided by neuroleptanalgesia,by continuous or intermittent administration of anopioid, or by medetomidine or detomidine.For these animals, the anaesthetic administrationmust be adjusted according to observation ofreflexes and cardiovascular response to surgicalstimulus.It should be noted that the gas analyser alsoaccurately measures inspired anaesthetic concentration,which may be substantially lower than theTABLE 2.2 MAC * values for halothane,isoflurane and sevoflurane in several speciesAnaesthetic Dogs Cats HorsesagentHalothane 0.9 1.1 0.9Isoflurane 1.4 1.6 1.3Sevoflurane 2.8 2.6 2.3* MAC = minimum alveolar concentration of anaestheticagent required to prevent purposeful movement in 50% ofanimals in response to a standard painful stimulus.

36 PRINCIPLES AND PROCEDURESvaporizer setting in rebreathing systems duringanaesthesia in large dogs, horses and ruminants.In the absence of an accurate measure of anaestheticconcentration delivered, administration ofan anaesthetic agent may be inadequate despite anapparently adequate vaporizer setting. In a retrospectivestudy of equine anaesthesia, it was foundthat horses were four times more likely to moveduring anaesthesia when an anaesthetic agentanalyser was not used (C. M. Trim, unpublishedobservations).Some monitors using the principles of infraredabsorption spectrometry cannot be used forhorses or ruminants as they will measure exhaledmethane and record the concentration ashalothane, for example the Datex Capnomac/Normac (Taylor 1990). Analysers that use higherwavelengths of infrared light should be unaffectedby methane (Moens et al., 1991).TABLE 2.3 Methods of assessing cardiovascularfunction in anaesthetized clinical patientsHeart rate● Palpation of arterial pulse● Oesophageal stethoscope● Electrocardiogram● Blood pressure monitor● Pulse oximeterTissue perfusion● Mucous membrane colour● Capillary refill time● Blood pressure● Bleeding at operative site● Observation of intestine colour● Urine outputArterial blood pressure● Palpation of peripheral pulse● Doppler ultrasound method● Oscillometric method● Arterial catheterizationComputerized anaesthetic administrationThe subject of computerized control of anaestheticadministration has already been discussed inChapter 1. This control is usually exerted by referenceto the changes in the electroencephalogram(EEG) with changes in depth of anaesthesia asdetermined by clinical signs or end-tidal concentrationsof halothane (Otto & Short, 1991; Ekstromet al., 1993; Johnson et al., 1994). The EEG may beinfluenced by a variety of factors occurring duringanaesthesia, including cerebrocortical depression,hypotension, hypoxaemia, and hypercapnia.Computerized EEG techniques, such as powerspectrum analysis (described by 80% or 95% spectraledge frequency), have potential application formonitoring depth of anaesthesia (Otto & Short1991; Johnson et al., 1994; Otto et al., 1996), but it ismost important to recognize the limitations of theraw EEG and its derivatives as discussed inChapter 1.Heart rate monitorsHeart rates measured before anaesthesia aregreatly influenced by the environment. Means(standard deviations, range) of heart rates obtainedby palpation from healthy cats at home were 118MONITORING THE CIRCULATIONThe heart rate, tissue perfusion, and bloodpressure of all anaesthetized animals shouldbe assessed at frequent regular intervals (Table2.3).FIG.2.6 The lingual artery is easily palpated in dogsmidline on the ventral surface of the tongue,adjacent tothe nerve and between the lingual veins.The arrow in thephotograph points to a line drawn adjacent to the lingualartery.

PATIENT MONITORING AND CLINICAL MEASUREMENT 37Facial arteryTransversefacial arteryThe lowest acceptable heart rates during anaesthesiaare controversial, but reasonable guidelinesare 55 beats/min for large dogs, 65 beats/minfor adult cats, 26 beats/min for horses, and50 beats/min for cattle. Heart rates should behigher in small breed dogs and much higher inimmature animals. It should be remembered thatheart rate is a major determinant of cardiac output,consequently, bradycardia should be treated ifblood pressure and peripheral perfusion are alsodecreased.Heart rate may be counted by palpation of aperipheral arterial pulse, such as the femoralartery in dogs and cats, lingual artery in dogs (Fig.2.6), facial, median or metatarsal arteries in horses(Fig. 2.7), and femoral, median, or auricular arteriesin ruminants and pigs.Lateralnasal arteryFIG.2.7 Sites for palpation of arterial pulse or catheterplacement for blood pressure measurement in horses.mean (SD 11, range 80 to 160) beats per minutecompared with mean 182 (SD 20, range 142 to 222)when obtained by electrocardiography in the veterinaryhospital (Sawyer et al., 1991).Oesophageal stethoscopeThe oesophageal stethoscope (Fig. 2.8) is a simplemethod of monitoring heart rate in dogs and cats.This monitor consists of a tube with a balloon onthe end which is passed dorsal to the endotrachealtube and into the oesophagus until the tip is levelwith the heart. The open end of the tube is connectedto an ordinary stethoscope headpiece, to aFIG.2.8 The oesophageal stethoscope.It may be used with a single earpiece or with a conventional stethoscopeheadpiece.This is a simple and inexpensive monitoring device for heart beat and respiratory activity.

38 PRINCIPLES AND PROCEDURESsingle earpiece that can be worn by the anaesthetistor surgeon, or connected to an amplifierthat makes the heart sounds audible throughoutthe room. This monitor provides only informationabout heart rate and rhythm; the intensity ofsound is not reliably associated with changes inblood pressure or cardiac output. Other electronicoesophageal probes are available to provide heartrate, and some also may produce an ECG andoesophageal temperature.ElectrocardiographyHeart rate and rhythm can be obtained from anelectrocardiograph using standard limb leads insmall animals, clip electrodes and ECG paste , andselecting ECG Lead II on the oscilloscope (Fig.2.9A). Poor contact of the electrodes to the skinfrom hair bunched in the clips, or close proximityto another electrical apparatus, such as the hotwater circulating pad, can result in electrical interferencethat obscures the ECG. The leads shouldnot be placed over the thorax as breathing willmove the electrodes and result in a wanderingECG baseline (Fig. 2.9B).Sinus arrhythmia is abolished when atropinehas been administered. Other arrhythmias, forexample second degree atrioventricular heartblock and premature ventricular contractions,may or may not require specific treatment (seeABCFIG.2.9 A Normal Lead II ECG from a Labrador anaesthetised with halothane. B ECG with a wandering baselineinduced by movement of leads as the dog breathes.This dog has a heart rate of 114 beats per minute,systolic arterialpressure of 96 mmHg,diastolic pressure of 46 mmHg,and mean pressure of 61 mmHg.C Normal base apex ECG andblood pressure recorded from a horse anaesthetised with isoflurane.

PATIENT MONITORING AND CLINICAL MEASUREMENT 39Chapter 20). Dogs with premature ventricular contractions(PVCs) from myocardial ischaemia as aresult of a road accident or gastric dilatation andvolvulus may be treated with antiarrhythmicdrugs before anaesthesia. Rather than completelyabolish all arrhythmias, the aim is to monitorblood pressure and tissue perfusion and adjustanaesthetic management to ensure that myocardialand respiratory depression are minimal.A frequently used monitor lead in equineanaesthesia is the ‘base-apex’ lead. The right armelectrode is clipped on the neck in the right jugularfurrow and the left arm electrode is passedbetween the forelimbs and clipped at the apex ofthe heart over the left 5th intercostal space severalinches from the midline. The left leg electrode isclipped on the neck or on the shoulder. Good electricalcontact is achieved with alcohol or electrodepaste. Lead I is selected on the electrocardiographand the normal configuration includes a negativeR wave (Fig. 2.9C). A bifid P wave is frequentlyobserved in the normal equine ECG.There is a high incidence of sinus arrhythmiaand first and second degree atrioventricular (AV)heart block in conscious unsedated horses(Robertson, 1990). In contrast, AV block duringanaesthesia is uncommon except when the horsehas been premedicated with detomidine, or supplementalintravenous injections of xylazine aregiven during anaesthesia. The appearance of thisarrhythmia during anaesthesia on any other occasionis cause for concern as this rhythm mayprogress within a few minutes to advanced heartblock (P waves only, no ventricular complexes)and cardiac arrest. Atrial fibrillation and VPCsoccur rarely but may require specific treatment ifassociated with hypotension.Tissue perfusionEvaluation of tissue perfusion can be done by consideringgum or lip mucous membrane colour, thecapillary refill time, and the blood pressure. Highmean arterial pressure does not guarantee adequatetissue perfusion. For example, when bloodpressure increases during anaesthesia in responseto a surgical stimulus, cardiac output may bedecreased due to increased afterload from peripheralvasoconstriction.Tissue perfusion is usually decreased when thegums are pale, rather than pink, and the capillaryrefill time (CRT) exceeds 1.5 seconds, or the meanarterial pressure (MAP) is less than 60 mmHg.When MAP is above 60 mmHg, palpation of thestrength of the peripheral pulse and observation oforal membrane colour and CRT should be used toassess adequacy of peripheral perfusion and cardiacoutput.Arterial blood pressureSystolic (SAP), mean (MAP), and diastolic (DAP)arterial pressures in awake healthy animals areapproximately 140–160 mmHg, 100–110 mHg, and85–95 mmHg, respectively. Excepting when premedicationhas included detomidine or medetomidineor when anaesthesia was induced withketamine or tiletamine, arterial blood pressure isdecreased from the awake value during anaesthesia.Arterial blood pressure is lower in paediatricpatients than in mature animals. For example,healthy 5 or 6-day-old foals anaesthetized withisoflurane had an average MAP of 58 mmHg.When the same foals were reanaesthetized 4–5weeks later, the average MAP had increased to 80mmHg, with a corresponding decrease in cardiacindex (Hodgson et al., 1990).Hypotension may be defined as a mean arterialpressure of less than 65 mmHg in mature animals.An MAP as low as 60 mmHg may be allowed indogs and cats provided that the mucous membranecolour is pink and CRT is 1 sec. This combinationof values may occur during inhalationanaesthesia at the time of minimal stimulationduring preparation of the operative site and beforethe onset of surgery. MAP is not usually allowed tofall below 65–70 mmHg for any length of time inanaesthetized horses because of the increased riskfor postanaesthetic myopathy. When hypotensionis documented, appropriate treatment can beinstituted, such as decreasing anaesthetic depth orcommencing or increasing the intravenous administrationof fluids or administration of a vasoactivedrug such as dopamine, dobutamine, or ephedrine.The outcome of untreated severe or prolongedhypotension may be unexpected cardiacarrest during anaesthesia or blindness or renal failureafter recovery from anaesthesia. In equine

40 PRINCIPLES AND PROCEDURESpractice, consequences also include the potentiallyfatal syndrome of postanaesthetic myopathy.An approximate estimate of blood pressure canbe made from palpation of a peripheral artery.However, in states associated with vasodilatation,a peripheral pulse can be palpated at pressures aslow as 50 mmHg and, in some cases, palpationalone does not suggest the urgency for treatmentthat is frequently warranted. Furthermore, it is notuncommon for heart rates to be within an acceptednormal range while blood pressure is low ordecreasing.Measurement of blood pressure can be madeeasily; equipment cost varies. The investment intime and money is worthwhile in animals at riskfor hypotension, such as small animals and horsesanaesthetised with inhalation agents, and inanimals with abnormalities likely to give rise tocomplications during anaesthesia. The leastexpensive techniques are the Doppler ultrasoundtechnique in dogs and cats, and direct blood pressuremeasurement using an anaeroid manometerin horses.Doppler ultrasound for indirect measurement of bloodpressureHair is first clipped from the skin on the palmarsurface of the paw of dogs and cats (Fig. 2.10).A probe covered with contact gel is placed overthe artery and taped in place (Fig. 2.11). Ultrasoundwaves emitted from one of the two piezoelectriccrystals embedded in the probe passesthrough the skin and deeper tissues. A structurewhich is stationary will reflect sound back to thesecond crystal without any frequency change(Stegall et al., 1968). Moving objects, such as erythrocytesand the artery wall, will reflect some ofthe sound at a different frequency (Doppler-shift).The change in frequency can be heard through aloudspeaker as an audible swooshing sound witheach pulse.A cuff is wrapped snugly around an extremityproximal to the probe, in dogs and cats with thecentre of the inflatable part of the cuff on the medialaspect of the limb. The cuff is connected to ananaeroid manometer and a bulb for manual inflationof the cuff with air (Fig. 2.12). In horses, thecuff is wrapped around the base of the tail with the125FIG.2.10 Sites for application of the Doppler probe forindirect measurement of arterial blood pressure in dogs.1 & 2:Ulnar artery on the caudal surface of the forelimb,above and below the carpal pad;3:cranial tibial artery onthe craniolateral surface of the hindlimb;4 & 5:saphenousartery on the medial surface of the flexor tendons and onthe plantar surface of the paw proximal to the foot pad;6:dorsal pedal artery;7:coccygeal artery on the ventralsurface of the tail.cuff air bladder centred over the ventral surface ofthe tail. The probe is taped distal to the cuff overthe coccygeal artery in the ventral midline groove.The coccygeal artery can be used for this techniquein adult cattle but the results are not reliable. Infoals and small ruminants, the probe can be tapedover the metatarsal artery on the lateral surface ofthe hind limb or the common digital artery on themedial side of the forelimb distal to the carpus.The cuff is secured around the limb above thehock or carpus. In pigs, the probe is most reliablewhen taped over the common digital artery onthe caudomedial aspect of the forelimb. The cuffshould be placed between the carpus and theelbow but, because of the triangular shape of theforearm, it may be unable to occlude blood flowwhen inflation of the cuff causes it to slip downover the carpus. The width of the air bladder withinthe cuff is important for accuracy; a bladder thatis too narrow will overestimate blood pressure andone which is too wide will underestimate it. A cuffthat is attached too loosely or slips down theextremity and becomes loose, will result in an erroneouslyhigh value.3647

PATIENT MONITORING AND CLINICAL MEASUREMENT 41FIG.2.11 Doppler-shift pulse detector.Onepiezoelectric crystal emits incident ultrasound signal whilethe other receives the reflected signal from cells in flowingblood.The frequency shift between the incident andreflected sound is converted to audible sound.FIG.2.12 Measurement of arterial pressure in a dog bytaping a Doppler probe over an artery distal to the carpalpad so that audible sounds of arterial pulses are emittedfrom the box. A blood pressure cuff is applied higher upthe limb and the anaeroid manometer attached to the cuffis used to identify systolic and diastolic pressures.To measure blood pressure, the cuff is inflated toabove systolic pressure to occlude the artery andno sound is heard. The pressure in the cuff isgradually released until the first sounds of bloodflow are detected at systolic pressure. As additionalpressure is released from the cuff, diastolic pressureis heard as a change in character of soundfrom a one or two beat sound to a multiple beatsound, to a muffling of sound, or to a growl. Thiswill occur 15 to 40 mmHg below systolic pressure.The sounds associated with diastolic pressure arewell defined in some animals but not at all clear inothers. In some animals a first muffling of beatsignals may occur 10 to 15 mmHg above thetrue diastolic pressure. In this event, the secondchange in beat signal will be more abrupt or distinct.Mean pressure can be calculated as one thirdof the pulse pressure (systolic–diastolic) plus diastolicpressure.A decrease in intensity of the pulsing sound,when the attachment and setting have been unchanged,is a reliable indication of decreased bloodflow. Furthermore, changes in cardiac rhythm areeasily detected by listening to this monitor.An investigation in cats comparing the Dopplerultrasonic method, using a cuff placed halfwaybetween the carpus and the elbow, with measurementsobtained from a femoral artery catheterrevealed that the indirect method consistentlyunderestimated the pressure by an average of14 mmHg (Grandy et al., 1992). Using this techniqueof measuring blood pressure in mature horsesusing a cuff width 48% of the circumference ofthe tail (bladder width 10.4 cm) systolic pressurewas underestimated and diastolic pressure overestimatedby approximately 9% (Parry et al., 1982). Inanother investigation, measurements of systolicarterial pressure in horses anaesthetized in dorsalrecumbency with halothane using a cuff 41% of thetail circumference was reasonably accurate but in5% of the horses this technique had an error rangeof ± 20 mmHg (Bailey et al., 1994).

42 PRINCIPLES AND PROCEDURESOscillometry for indirect measurement of blood pressureDevices that non-invasively measure peripheralblood pressures using the oscillometric methodgenerally operate by automatically inflating a cuffplaced around an extremity (Fig. 2.13). As pressureis released from the cuff, pressure changes occurringwithin the cuff as a result of adjacent arterialpulsations are detected by a transducer within themonitor. Values for systolic, diastolic, and meanarterial pressures, and heart rate are digitallydisplayed and the monitor can be programmed toautomatically measure at a specific time interval.Artefactual pressure changes induced in thecuff by movement of the extremity, for example,during preparation of the surgical site, will eitherinduce abnormal readings or prevent the monitorfrom obtaining a measurement.Published results of comparisons betweenmeasurements of blood pressure obtained by indirectand direct methods have identified variabilityaccording to the monitor used, cuff size, and site ofapplication of the cuff. The closest correlationsbetween direct and indirect measurements haveoccurred in anaesthetized dogs, using cuff widthsbetween 40 and 60% of the circumference of the extremity,at systolic pressures greater than 80mmHg.An evaluation of the DINAMAP model 1846SXcomparing direct measurement of blood pressurefrom the dorsal pedal artery with measurementsobtained from a cuff applied at various sites on theforelimb, hindlimb, and tail determined that theclosest correlations were from a cuff on the tail orat a proximal site on the hindlimb (Bodey et al.,1994). The tail cuff delivered the best reproducibilityin conscious dogs and although the systolicpressure obtained from the tail cuff was substantiallyhigher than direct values, the tail systolicpressure correlated best with changes in directblood pressure. In anaesthetized dogs, mean pressuresobtained from a cuff applied to a proximalsite on the hindlimb were significantly correlatedto mean direct pressures, whereas systolic and diastolicpressures were on average 8 and 5 mmHg,respectively, higher than directly measured pressures(Bodey et al., 1994).Measurements obtained from a DINAMAPmodel 8100 using a cuff around the metacarpus ormetatarsus and cuff width 40–60% of limb circumferencewere compared with direct measurementof blood pressure from a catheter in the abdominalaorta of medium to large-sized anaesthetized dogs(Sawyer et al., 1991). No differences were found inFIG.2.13 The DINAMAP 8300 (Sharn,Tampa,Florida,USA) utilizes the oscillometric method of measuring arterial bloodpressure non-invasively.

PATIENT MONITORING AND CLINICAL MEASUREMENT 43measurements recorded from cuffs applied toeither forelimb or hindlimb. Differences betweenindirect and direct measurements were statisticallysignificant but not considered to be clinicallysignificant. In general, indirect pressure measurementswere lower than direct measurementsand indirect systolic pressure was found to havethe most accurate correlation. At systolic pressuresof lower than 80 mmHg, indirect pressuremeasurements were 6 to 15% higher than directmeasurements.In a clinical study of dogs anaesthetized for avariety of soft tissue surgical procedures, indirectmeasurements of blood pressure using theDINAMAP model 8300 and a cuff around themetatarsus with the arrow directly over the pedalartery were compared with pressures recordedfrom the dorsal pedal artery in the opposite limb(Meurs et al., 1996). It was concluded that measurementstaken at a single point in time varied widelybetween indirect and direct methods, and that singlevalues do not provide reliable informationabout changing blood pressure. When five sequentialreadings over 30 minutes were averaged, thismodel had a sensitivity of 100% (i.e. the methodcorrectly identified a direct MAP of less than60 mmHg 100% of the time) in this population ofanimals, of which 73% were normovolaemic(Meurs et al., 1996). A positive predictive value of80% was calculated, which indicates that the abilityof this method to detect correctly a true MAP ofless than 60 mmHg was 80% and that the methodincorrectly predicted hypotension 20% of the time.Six sites for placement of the cuff have beenevaluated in anaesthetized cats using theDINAMAP model 8300 (Sawyer, 1992). The greatestaccuracy was obtained with the cuff placedbetween the elbow and carpus with the cuff arrowon the medial side of the limb. An evaluation of theDatascope Passport revealed that this model didnot accurately estimate direct blood pressure incats (Branson et al., 1997).In horses, the DINAMAP is a commonly usedmonitor utilizing the oscillometric method ofblood pressure measurement. The cuff is wrappedaround the tail of mature horses or around thehind limb near the metatarsal artery in foals. Thecuff should not be wrapped tightly. Some investigatorshave recommended that the tail cuff beplaced close to the base of the tail, but in thisauthor’s opinion more accurate readings areobtained with the cuff applied approximately10cm from the base of the tail, where the tail diameteris constant for the length of the cuff. Earlyinvestigations of the DINAMAP confirmed accurateand clinically useful values for arterial pressureusing a cuff width 24% of the tailcircumference in ponies (Geddes et al., 1977) and25–35% in horses (Latshaw et al., 1979; Muir et al.,1983). However, measurements were inaccurate atheart rates of less than 25 beats/minute. Our experienceusing a Model 8300 DINAMAP and a cuffwidth 35–40% of the tail circumference ratio (childor small adult cuff for a mature horse dependingon tail thickness and the amount of hair) has beenthat the mean arterial blood pressure valueobtained from this monitor is usually the same asthat obtained by direct blood pressure measurement.Occasionally, the DINAMAP recorded pressures10 to 20 mmHg higher than the true meanarterial pressure.In summary, indirect method of measurementof blood pressure provides useful information inmost horses, but may produce erroneous valuesin a small number. Consequently, blood pressureshould be measured by direct means wheneverCranialtibial arteryDorsalpedal arteryFIG.2.14 Sites for insertion of arterial catheters on thecranial aspect of the right hindlimb of a dog.

44 PRINCIPLES AND PROCEDURESpossible in horses at risk of developing lowblood pressure, for example, during inhalationanaesthesia.Direct measurement of blood pressureMeasurement of arterial blood pressure directly isaccomplished by insertion of a 20 gauge, 22 gaugeor, in cats and small dogs, a 24 gauge catheter asepticallyinto a peripheral artery, usually the dorsalpedal artery, anterior tibial or femoral artery indogs and cats (Fig. 2.14), the lateral nasal, facial,transverse facial, or metatarsal artery in horses(Fig. 2.7), or an auricular artery in ruminants andpigs (Fig. 2.15). The catheter is connected by salinefilledtubing to either an anaeroid manometer (Fig.2.16) or an electrical pressure transducer (Fig. 2.17)for measurement of arterial pressure. Either an airgap or a commercially available latex diaphragm(Fig. 2.18) should be maintained next to theanaeroid manometer to prevent saline entering themanometer and to maintain sterility. An optionaladdition is a continuous flushing device (Fig. 2.19)that can be inserted between the manometer ortransducer and the artery. This device is connectedto a bag of saline that has been pressurized to200mmHg and will deliver 2–4 ml saline/hour tohelp prevent clotting of blood in the catheter.The needle of the anaeroid manometer deflectsslightly with each beat and the value at the upperFIG.2.15 Ink lines have been drawn over the auriculararteries in this goat.FIG.2.16 Inexpensive apparatus for the directmeasurement of mean arterial blood pressure.deflection of the needle is slightly less than thevalues obtained by direct measurement (Riebold& Evans 1985). For accurate measurement, theair–saline junction in the tubing connected tothe manometer, or the electrical transducer, arezero reference points and should be placed levelwith the right atrium or the point of the shoulderwhen the horse is in dorsal recumbency or levelwith the sternal manubrium when in lateralrecumbency.The anaeroid manometer costs very little butprovides only MAP. The initial cost of an electrocardiographand blood pressure monitor can behigh, however, the electrical transducer does providemuch more information, such as digitalvalues for SAP, MAP and DAP, heart rate, and awaveform that can be observed on the oscilloscopeor paper printout (Fig. 2.20).Important advantages of direct measurement ofblood pressure are the reliability of measurementand the ability continuously to observe the pressureand immediately detect an abnormality (Fig. 2.21).

PATIENT MONITORING AND CLINICAL MEASUREMENT 45FIG.2.17 Direct measurement of blood pressure in a horse using a catheter in the facial artery connected by saline-filledtubing to an electrical transducer.Central venous pressureThe apparatus for measurement of central venouspressure (CVP) can include a commercially-availableplastic venous manometer set or be constructedfrom venous extension tubes and acentimetre ruler (Fig. 2.22). A catheter of sufficientlength is introduced into the jugular vein andadvanced until its tip lies in the cranial vena cava.The distance the catheter tip has to be introducedis, initially, estimated by measurement of length,but once the catheter is connected to the manometerits position may be adjusted until the level offluid in the manometer tube moves in time withthe animal’s respiratory movements. In dogs andcats the introduction of a catheter into the jugularvein is often greatly facilitated by laying theanimal on its side and extending its head and neckover a pillow or sandbag. If the catheter is to be leftin position for a long time it is kept patent with adrip infusion or the catheter is kept filled withheparin-saline solution (10 units/ml) betweenmeasurements. Readings may be taken at anytime. If an intravenous drip is used it is turned fullon and the stopcock manipulated first to fill themanometer tube from the bag or bottle and then toconnect the manometer tube to the catheter. Thefall of fluid in the manometer is observed andshould be ‘step-like’ in response to respiratorypressure changes. The central venous pressure isread off when fluid fall ceases.Venous pressures being low, the margin of errorintroduced by inaccuracies in obtaining a suitablereference point to represent zero pressure may beclinically significant. Whatever apparatus is used,the zero of the scale should be carefully located,either by placing the patient and manometer inclose proximity or by using a spirit level to ensureaccuracy. The ideal reference point is the meanpressure in the right atrium but for practical purposesthe most appropriate is the sternal manubriumwhich is easily located and is related to theposition of the right atrium in all animals, irrespectiveof body position. Measurements of CVP are notsignificantly affected by positioning the animal inright or left recumbency or by catheter size,although oscillations are more easily observedwith a 16 gauge catheter (Oakley et al., 1997).CVP is used in the evaluation of adequacyof blood volume, with the normal range being 0 to5 cm H 2 O in small animals. Hypovolaemia is

46 PRINCIPLES AND PROCEDURESmmHg12080ABmmHg120dP/dt80CDFIG.2.20 Waveforms from direct measurement of thearterial pressure.A Good trace.B Recording of the samepressure but with excessive damping,systolic pressurelow,diastolic pressure high,mean arterial pressureunchanged.C Recording of same pressures but withresonance,systolic pressure apparently increased whilediastolic pressure reduced,mean pressure unchanged.D Illustration of how left ventricular contractility may beestimated from the rate of rise of pressure during earlysystole (dP/dt) while the shaded area gives an index ofstroke volume.indicated when the CVP is less than 0 cmH 2 O. Anincrease in pressure above 12 cmH 2 O may becaused by fluid overload or cardiac failure.FIG.2.18 Pressure transfer unit in which a latexdiaphragm isolates the anaeroid manometer from thefluid-filled catheter line.These units are presterilized anddisposable.Left atrial pressure (pulmonary artery wedgepressure)Left heart failure may precede that of the right sideand precipitate pulmonary oedema without a risein central venous pressure. The pulmonary arteryFIG.2.19 Continuous infusion valve for attachment to a pressure transducer. A pressurized bag of intravenous fluid isconnected to the plastic tube to give a continuous infusion of 3 ml per hour.With this particular version,rapid flushing ofthe manometer line is achieved by pulling the rubber tag on top of the valve.

PATIENT MONITORING AND CLINICAL MEASUREMENT 47FIG.2.21 Top:pressure trace from a dog’s femoral artery.Bottom:Lead II electrocardiogram.Circulatory failure from anoverdose of pentobarbital.Note that while the pressure trace shows the circulation to be ineffective,the ECG trace islittle different from normal – heart rate monitors relying on the QRS complex for detection of the heart beat would,under these circumstances,show an unchanged heart rate and in the absence of a blood pressure record encourage theerroneous belief that all was well with the circulatory system.Balanced electrolytesolution withadministration set3–way stopcockFluid-filledmanometercalibratedin cmwedge pressure (PAWP) is used as a measure ofthe left atrial filling pressure. A balloon-tipcatheter is introduced into the jugular vein and itstip advanced into the heart. Inflation of the balloonwith 0.5 ml air facilitates floating the catheter in thebloodstream into the pulmonary artery and thenthe catheter can be advanced until the tip iswedged in a small pulmonary vessel. The measurementis made using the same apparatus as isused for the measurement of central venous pressureor using an electrical pressure transducer.Care must be taken to ensure that vessel occlusionis not maintained between measurements or pulmonaryinfarction may occur. If a balloon catheteris used the balloon should only be inflated whilemeasurements are made and if a simple catheter isused it should be slightly withdrawn from thewedged position between measurements.Manometer connectedto jugular catheter(covered by bandagearound neck)Zero on scalecorresponds withthoracic inletFIG.2.22 Schematic diagram of the apparatus formeasurement of central venous pressure.Cardiac outputThe measurement of cardiac output is not onewhich is routinely carried out in clinical anaesthesia.For research purposes it may be determined byinvasive methods such as the direct or indirect

48 PRINCIPLES AND PROCEDURESFick estimations, dye (indocyanine green) or thermaldilution. Modern non-invasive methodsinclude Doppler shift measurements, includingcolour Doppler displays, but the cost of the necessaryapparatus renders them impracticable formost veterinary purposes.Blood lossMonitoring blood loss should include measuringthe volume of blood aspirated from a body cavity,estimating free blood on drapes around the surgicalsite, and counting blood-soaked gauze swabs.The volume of blood lost on the swabs may beestimated or the swabs weighed and, after theweight of the same number of dry gauze swabshas been subtracted, applying the formula that 1gweight equals 1 ml blood. Measurement of packedcell volume is not useful in acute blood loss as thisvalue will not change initially. Once large volumesof balanced electrolyte solution have been infusedthe packed cell volume and total protein concentrationswill decrease. When evaluating packedcell volume changes it is important to consider thatanaesthesia per se will result in sequestration of redblood cells in the spleen and decrease the packedcell volume by up to 20%.In the conscious animal, loss of blood volume isinitially compensated for by increased heart rateand cardiac contractility, together with peripheralvasoconstriction. These physiological responsesare blunted or abolished during anaesthesia.Consequently, the significance of the blood lossmay not be appreciated owing to maintenance of anormal heart rate. Furthermore, it should beremembered that when mean arterial pressure isdecreasing in response to haemorrhage, cardiacoutput decreases to a greater extent (Fig. 2.23)(Weiskopf et al., 1981).Measurement of arterial pressure is an importantstep in the management of blood loss as oxygendelivery to tissues is impaired when meanarterial pressure decreases below 60 mmHg. Thepotential impact of blood loss on the patientmay be evaluated better by assessing the volumeof blood loss against the total blood volume.The blood volume varies between species and isusually assessed in mature animals as 86 ml/kgbody weight in dogs, 56 ml/kg in cats, 72 ml/kg inPercent decrease0-10-20-30-40-50Haemorrhage % of blood volume10% 20% 30%Heart rateMean arterial pressureCardiac outputFIG.2.23 Cardiovascular responses to gradedhemorrhage in five isoflurane-anaesthetized dogs.Resultsare presented as percent change from values measuredbefore blood loss (adapted from Weiskopf et al.,1981).draught horses and ponies, 100ml/kg in Thoroughbredsand Arabians, 60 ml/kg in sheep.Blood volume of paediatric patients may be50% greater than the blood volume of the matureanimal. The percentage of this volume that the animalcan lose before circulatory shock ensuesdepends to a large extent on the physical status ofthe patient, the depth of anaesthesia, and the supporttreatment provided. The maximum blood lossallowed before giving a blood transfusion isusually 20% of the estimated blood volume, however,in some animals up to 40% of the total bloodvolume may be lost without onset of hypotensionor hypoxia if the patient has no major preanaestheticillness, is ventilated with oxygen, the depthof anaesthesia is lightened, balanced electrolytesolution is infused intravenously, and vasoactivedrugs are administered as needed.MONITORING THE RESPIRATORY SYSTEMVisual observation of respiratory rate and depth ofbreathing is a basic estimate of adequacy of breathing.The respiratory rate may be counted by observationof chest movement or movement of thereservoir bag on the anaesthesia machine. Theexcursion of the chest, abdomen, or bag should beobserved to gain an impression of the depth ofbreathing. In general, except possibly in horses, aspontaneous rate of 6 breaths/min or less constitutesrespiratory depression. Respiratory rates of10 breaths/min or greater may provide adequate

PATIENT MONITORING AND CLINICAL MEASUREMENT 49ventilation but the breaths may be shallow andresult in hypoventilation. Chest wall movementwith no corresponding movement of the bag iscommon with complete respiratory obstruction.Rate monitors and apnoea alarmsRate monitors and apnoea alarms may use a thermistoreither connected to the endotracheal tubeor placed in front of a dog’s nose. The thermistordetects temperature differences between inspiredand exhaled gases to produce a signal that drives adigital rate meter to make a noise which varies inintensity or pitch in time with the animal’s breathing.An alarm sounds if a constant gas temperatureis detected. Like the oesophageal stethoscope thatcounts only heart rate, the respiratory rate monitorregisters rate only and not adequacy of ventilation.Tidal and minute volume monitorsThe volume of each breath (tidal volume) and thevolume of gas inhaled or exhaled per minute(minute volume) can be measured in small animalsby attaching a gas meter such as a Wright’srespirometer within the circle circuit or to theendotracheal tube. The respirometer has a lowresistance to breathing and is reasonably accurateover volumes ranging from 4 l/min to 15 l/minbut under-reads below 4 l/min. Gas meters sufficientlylarge for adult horses are not routinelyutilised but domestic dry-gasmeters can be incorporatedin large animal breathing systems.Measurement of arterial pH and blood gastensionsMeasurement of the partial pressure of carbondioxide (PaCO 2 ) in a sample of arterial blood byblood gas analysis is the best monitor of ventilation.Arterial blood may be collected from anyperipheral artery used for blood pressure measurement.A small amount of 1:1000 heparin shouldbe drawn into a 3 ml syringe using a 25 gauge needleand the plunger withdrawn to wash the insideof the syringe with heparin. Excess heparin is thensquirted from the syringe leaving only syringedead space filled with heparin and no bubbles. A1–2 ml sample of blood is collected from mostanimals. A micro technique using 0.2 ml blooddrawn into a 1 ml syringe can be used for verysmall animals.The blood sample should be collected anaerobicallyslowly over several respiratory cycles andwithout aspirating any air bubbles. After expressinga drop of blood and any bubbles from the needle,the syringe should be sealed either with aspecial cap or by inserting the tip of the needle intoa rubber stopper. The syringe should be invertedseveral times to mix the blood with the heparin. Ifthe sample is not analysed immediately, thesyringe should be immersed in a container containingice and water. The temperature of the animalshould be measured at the time of sampling.The blood sample is then introduced intoequipment incorporating electrodes measuringpH, PCO 2 and PO 2 . The machine may use themeasured values to compute bicarbonate (HCO 3 ),total CO 2 (TCO 2 ), base excess (BE) and oxygen saturation(SaO 2 ). The patient’s temperature isentered into the blood gas analyser for appropriateadjustment of pH and PO 2 . The patient’s haemoglobinconcentration must be known for an accuratemeasure of base excess. Fully automated pHand blood gas analysers are highly accurate butexpensive. Portable and less expensive equipmentis available, for example, StatPal® (PPGTABLE 2.4 Normal values for pH,PaCO 2 ,andPaO 2 in mature conscious unsedated animals.Values for PaCO 2 ,and PaO 2 given as pKa(mmHg)Species pHa PaCO 2 PaO 2 ReferencesDogs 7.40 4.67 13.6 Horwitz et al.,(35) (102) 1969Cats 7.34 4.5 13.7 Middleton et al.,(34) (100) 1981Horses 7.38 5.0–6.1 13.5 Steffey et al.,1987;(38–46) (100) Clarke et al.,1991;Wagner et al.,1991;Wan et al.,1992Cattle 7.40 5.28 12.0 Gallivan et al.,1989(39) (89)Sheep 7.48 4.4 12.3 Wanner &(33) (92) Reinhart,1978Goats 7.45 5.48 12.6 Foster et al.,1981(41) (95)

50 PRINCIPLES AND PROCEDURESIndustries, Inc., La Jolla, California, USA) andi-STAT (Sensor Devices, Inc., Waukesha, Wisconsin,USA), although the cost of individual analyses ishigher.Normal values for PaCO 2 in conscious unsedatedanimals are given in Table 2.4. IncreasedPaCO 2 (hypercapnia) is a direct consequence ofhypoventilation and commonly occurs duringanaesthesia. PaCO 2 values exceeding 8 kPa(60mmHg) are indicative of significant respiratorydepression. A decrease in PaCO 2 (hypocapnia)is due to increased ventilation. A PaO 2 less than2.6 kPa (20 mmHg) causes cerebral vasoconstrictionand cerebral hypoxia.Hypercapnia in dogs and cats, particularly duringhalothane anaesthesia, may be associated witharrhythmias such as premature ventricular depolarizations.In these animals intermittent positivepressure ventilation (IPPV) will result in normalcardiac rhythm within a few minutes. Hypercapniain horses during anaesthesia may causestimulation of the sympathetic nervous system,increased blood pressure and cardiac output(Wagner et al., 1990; Khanna et al., 1995). Adverseeffects of hypercapnia are observed in some horsesas tachycardia of 60–70 beats/min, or hypotensioncaused by decreased myocardial contractility.These abnormalities are corrected within 5–10 minutes by initiating controlled ventilation.More frequently, the effects of hypoventilationduring inhalation anaesthesia are manifested as aninadequate depth of anaesthesia despite a vaporisersetting that should provide a sufficient depth ofanaesthesia. In these animals, controlled ventilationexpands the lungs, thereby improving uptakeof anaesthetic agent and resulting in increaseddepth of anaesthesia.Arterial oxygenation can be monitored bydirect measurement of the partial pressure of oxygenin a sample of arterial blood (PaO 2 ) or indirectlyby attaching a sensor to the tongue, for example,and measuring oxygen saturation of arterialblood (pulse oximetry). PaO 2 values are influencedby the inspired oxygen tension (P I O 2 ), adequacyof ventilation, cardiac output, and bloodpressure. A PaO 2 of 12–14.6 kPa (90–110 mmHg) isnormal in unsedated animals at sea level and PaO 2values less than 8 kPa (60 mmHg) constitutehypoxaemia.The maximum possible PaO 2 is governed bythe PiO 2 and animals breathing oxygen may havePaO 2 values up to five times greater than whenbreathing air. The partial pressure of oxygen at thealveolar level (PaO 2 ) can be calculated from thefollowing formula:PaO 2 = [(barometric pressure – P water vapour )× FIO 2 ] – PaCO 2 ,where the value for water vapour is 6.25 kPa (47mmHg) and FIO 2 is the fractional concentration ofoxygen in inspired gas. Values for PaO 2 greaterthan 53.2 kPa (400 mmHg) are expected in healthydogs breathing oxygen. Horses and ruminants aresubject to lung collapse during recumbency andanaesthesia and, consequently, ventilation andperfusion are mismatched within the lung, resultingin a lower PaO 2 .Hypoxaemia may develop in dogs and catsduring anaesthesia or recovery as a result ofhypoventilation when breathing air. This situationis most likely to occur in old animals, animals withhypotension, pneumothorax, pulmonary disease,CNS depression from metabolic disease, or afteradministration of opioids. Hypoxaemia may alsodevelop during general anaesthesia as a result ofsevere lung collapse. Patients at greatest risk aresmall animals during thoracotomy or repair of aruptured diaphragm, foals with pneumonia andhorses with abdominal distension from pregnancyor colic. Cyanosis may be suspected but is notalways obvious, especially in horses. Monitoringby blood gas analysis or pulse oximetry will confirmlow PaO 2 or SaO 2 .Pulse oximetryPulse oximetry is a non-invasive method ofcontinuously measuring haemoglobin oxygen -saturation (SpO 2 ). The sensor consists of lightemittingdiodes (LEDs) that emit light in thered (660 nm) and infrared (940 nm) wavelengthsand a photodetector that measures the amountof light that has been transmitted through tissues(Tremper & Barker, 1990). The principles ofmeasurement are based on the different lightabsorption spectra of oxyhaemoglobin and reducedhaemoglobin, and the detection of a pulsatilesignal.

PATIENT MONITORING AND CLINICAL MEASUREMENT 51FIG.2.24 Pulse oximeter (Heska Corporation,Fort Collins,Colorado,USA) showing the dog’s heart rate andhaemoglobin oxygen saturation in waveform and as a digital number.Pulse oximeters display a digital record of pulserate, with an audible beep, and some monitors displaythe oxygen saturation waveform (Fig. 2.24). Alimit for acceptable saturation can be entered intothe monitor, allowing an alarm to sound whenlower values are sensed. The pulse rate displayedon the oximeter must correspond to the rateobtained by palpation or ECG, and the sensor be inposition for at least 30 seconds, before the measurementcan be assumed to be accurate. The shapeof the sensor, thickness of tissue placed within thesensor, the presence of pigment and hair, andmovement of the patient, can be responsible forthe oximeter failing to measure oxygen saturation.It may be impossible to obtain a reading from apulse oximeter when peripheral vasoconstrictionis severe, for example, after administration ofmedetomidine in dogs or patients in circulatoryshock.Arterial oxygen saturation (SaO 2 ) is the percentof haemoglobin saturated with oxygen. The relationshipbetween PaO 2 and SaO 2 is not linearbecause haemoglobin changes its affinity for oxygenat increasing levels of saturation, and the associationis further altered by pH and temperature ofthe blood (Fig. 2.25). Oxygen delivery to tissues isdefined by the oxygen content (oxygen combinedwith haemoglobin and dissolved in plasma) andthe cardiac output, although oxygen delivery to anindividual organ is influenced by the blood flow tothat specific organ. Hypoxia is inadequate tissueoxygenation caused by low arterial oxygen contentor inadequate blood flow. An animal with alow haemoglobin will have low blood oxygencontent despite PaO 2 and SaO 2 being withinHaemoglobin saturation (%)10080604020Venoussat. 75%PO 2 40Arterialsat. 97%PO 2 1000 00 20 40 60 80 100PO 2 (mmHg)20161284O 2 content (ml/100ml)FIG.2.25 Graph depicting the relationship betweenPaO 2 ,haemoglobin oxygen saturation SaO 2 ,and oxygencontent.

52 PRINCIPLES AND PROCEDUREStheir normal ranges. Anaesthetic managementof anaemic patients should, therefore, includeadministration of 100% inspired oxygen and cardiovascularsupport.A pulse oximeter detects inadequate blood oxygenation,which should be taken as an indicationto supplement the animal’s inspired oxygen concentrationand to search for the cause. A pulseoximeter is a valuable monitor for animals anaesthetizedwith injectable anaesthetic agents andbreathing air, or during inhalation anaesthesia inpatients with pulmonary disease or traumatic pulmonarycontusions or pneumothorax, and duringthoracotomy or major surgery in the cranialabdomen. It is also important to keep track of oxygenationin animals during recovery from anaesthesia,in patients with partial airway obstruction,or when ventilation is depressed or impairedby systemic opioid administration or residualpneumothorax after thoracotomy or ruptured diaphragmrepair.The pulse oximeter is particularly valuablebecause it provides an immediate monitor ofdecreased oxygen saturation, so that correctivetreatment can be initiated before respiratory orcardiovascular failure develops. Evaluation of thepatient should take into account the fact that thepulse oximeter does not measure carbon dioxideconcentration or blood pressure and may continueto read satisfactorily in the presence of hypotension.However, it can provide a warning of asevere decrease in tissue blood flow caused byhypotension or decreased cardiac output byabruptly failing to obtain a signal. Loss of signalmay also occur spontaneously with no change inthe patient’s condition and measurement isrestored by changing the position of the probe.Compression of the base of the tongue between theendotracheal tube and the jaw may decrease bloodflow and signal acquisition from a probe clipped tothe tongue.Different body sites in dogs have been evaluatedfor accuracy of measurement of SaO 2 . In one investigation,a multisite clip probe placed on the lip,tongue, toe web, and the tip of the tail gave accurateand reliable estimations of SaO 2 values duringconditions of full haemoglobin saturation andmoderate haemoglobin desaturation (92%) (Husset al., 1995). In this study, the human finger probewas accurate only when placed on the dog’s lipand when haemoglobin saturation was complete.The lip was found to be the best site in consciousanimals. Another study of conscious dogs in anintensive care unit found that a circumferentialpulse oximeter probe around a digit or themetatarsus produced excellent correlationsbetween pulse oximeter and SaO 2 values (Fairman,1993). An evaluation of the Ohmeda Biox 3700with a human ear probe applied to the tongueprovided an accurate evaluation of SaO 2 (Jacobsonet al., 1992). The pulse oximeter underestimatedSaO 2 at higher saturations and overestimatedSaO 2 at saturations < 70%. However, as theauthors pointed out, detection of hypoxaemia ismore important than measurement of the exactdegree of hypoxaemia. In our experience, a rectalsensor is useful for monitoring oxygenation indogs and cats recovering from anaesthesia.Different monitors, types of sensors, and alternativessites for measurement have been evaluatedin horses (Whitehair et al., 1990; Chaffin et al.,1996). The Ohmeda Biox 3700 pulse oximeter andthe Physio-Control Lifestat 1600 pulse oximeterwere evaluated in mature horses using the humanear lobe probe (Whitehair et al., 1990). Measurementswere obtained from the tongue and the ear,with the most accurate measurements obtainedfrom the tongue; the oximeters failed to detect apulse at the nostril, lip, or vulva. The resultsrevealed that both oximeters tended to underestimatesaturation by 3.7%, with 95% of the oxygensaturation values within 1 percent above or 8 percentbelow SaO 2 (Whitehair et al, 1990). TheNellcor N-200 pulse oximeter was evaluated inanaesthetized foals using a fingertip probe(Durasensor DS-100A) (Chaffin et al., 1996).Attachment of the probe to the tongue or ear of thefoals slightly underestimated SaO 2 within therange of 80–100% saturation. In our experience, asensor applied to the Schneiderian membrane inthe nostrils yields the most accurate results inhorses.Reflectance pulse oximeters detect changes inabsorption of light reflected from tissues, ratherthan transmitted through tissues as just described(Watney et al., 1993; Chaffin et al., 1996). Attachmentof a reflectance probe designed for thehuman forehead to the ventral surface of the base

PATIENT MONITORING AND CLINICAL MEASUREMENT 5360CO 2mm0INEXCO 2 mm049O 2 %9487N 2 O%00ISO%1.21.1RESPFIG.2.26 Capnograph (redrawn) from a foal anaesthetized with isoflurane and an end-tidal concentration of 1.1%.Thefoal is breathing spontaneously at 10 breaths per minute and the end-tidal concentration of carbon dioxide is 6.5 kPa (49mmHg),confirming a degree of hypoventilation.10of the tail in foals had 100% sensitivity fordetecting SaO 2 < 90% but consistently underestimatedthe actual value (Chaffin et al., 1996).Therefore, this probesite combination will incorrectlyidentify some foals as being hypoxaemic.CapnographyCapnography indirectly estimates PaCO 2 bymeasuring the concentration of CO 2 in expiredgas. Capnography is also useful for diagnosis ofmechanical problems in anaesthetic circuits, airwayobstruction, and cardiogenic shock. Gas isaspirated from the endotracheal tube or Y-piece(Matthews et al., 1990) and the capnometer measuresCO 2 concentration by infrared absorption(Fig. 2.5). Gases leaving the analyser should bedirected back into the anaesthetic circuit or into thescavenging system. The capnometer providesbreath-by-breath numerical values for carbon dioxideconcentration and some monitors display theCO 2 waveform (capnograph). The upward slope ofthe waveform represents expiration and the highestvalue is the end-tidal CO 2 (E T CO 2 ). The downwardslope occurs during inspiration and theinspiratory baseline should be zero (Fig. 2.26).Falsely low measurements of E T CO 2 may occurwith the use of non-rebreathing circuits, becausethe high gas flow results in dilution of expiredgases, and in animals with very small tidal volumesor that are panting. Bumps and dips in theexpiratory plateau may be caused by spontaneousrespiratory efforts, heart beats, and movements ofthe animal by the surgeon. Changes in E T CO 2 orwaveform are useful indicators of significant alterationin physiological status or equipment malfunction(Table 2.5). A sudden decrease in E T CO 2 iscause for concern and the patient and equipmentshould be checked for hypotension, cardiac arrest,or equipment leaks and disconnection. Exhaledwater vapour condenses in the sampling tubingand water trap but when water enters the monitorunpredictable and bizarre values are obtained.Significant correlation between E T CO 2 andPaCO 2 has been recorded in dogs and horses, withthe PaCO 2 exceeding the E T CO 2 by 1.00–4.65 kPaTABLE 2.5 Troubleshooting the capnogramUnexpectedly low E T CO 2Cardiac arrestSampling line disconnected or brokenEndotracheal tube cuff deflatedTidal volume too smallFailure to read zero on inspiration(rebreathing)Large apparatus deadspaceExhausted soda limeExpiratory valve on circle stuck in open positionBreathing rapid and shallowProlonged inspiratory or expiratory slopeSlow inspiratory timeObstruction or crack in the sampling lineGas sampling rate too slowLeak around connection to circle or tracheal tubeLung disease

54 PRINCIPLES AND PROCEDURES(1–35 mmHg) depending on the degree ofpulmonary shunting and lung collapse. E T CO 2values exceeding 6.7 kPa (50 mmHg) representincreased PaCO 2 and significant hypoventilation.However, when E T CO 2 is normal, PaCO 2 may benormal or increased and when E T CO 2 is low,PaCO 2 may be low, normal or increased.Therefore, if blood gas analysis is available onedirect measurement of PaCO 2 is advisable whenthe E T CO 2 value is normal or low, particularly indogs with pulmonary disease or during thoracotomy,and anaesthetized horses at risk for severelung collapse, such as colic patients or foals.The difference between PaCO 2 and E T CO 2 isusually less in dogs than in horses. In a group ofmechanically ventilated dogs in intensive care, theE T CO 2 was on average 0.67 kPa (5 mmHg) lessthan PaCO 2 (Hendricks & King, 1994). Nonetheless,there was sufficient variation to concludethat although high E T CO 2 confirms the presenceof hypoventilation, some patients may be erroneouslyidentified as having adequate ventilation.In anaesthetized healthy mature horses an averagedifference of 1.6 kPa (12 mmHg), range 0–4.3kPa (0–32 mmHg) was recorded during halothane(Cribb, 1988; Moens, 1989) and 1.9 kPa (14 mmHg)during isoflurane anaesthesia (Cribb, 1988). Astronger correlation between E T CO 2 and PaCO 2was identified during halothane compared withisoflurane anaesthesia (Meyer & Short, 1985;Cribb, 1988). No significant increase in PaCO 2 –E T CO 2 difference was recorded with increasedduration of anaesthesia (Cribb, 1988; Moens,1989).In one study of 110 horses, the PaCO 2 –E T CO 2 differencewas greater in heavier horses and wasincreased when horses were in dorsal recumbencycompared with lateral recumbency (Moens, 1989).A mean PaCO 2 –E T CO 2 difference of 1.8 ± 0.9 kPa(13.4 ± 6.9 mmHg; range 0–37.5 mmHg) was measuredin 125 horses anaesthetized with isofluranein dorsal recumbency for colic surgery (Trim, 1998).Spontaneously breathing foals anaesthetized withisoflurane had a mean PaCO 2 –E T CO 2 difference inthe first hour of anaesthesia of 0.9 kPa (7 mmHg)which increased over 90 minutes of anaesthesia to1.7 kPa (13 mmHg), coincident with an increase inPaCO 2 (Geiser & Rohrbach, 1992). These authorswere unable accurately to predict PaCO 2 fromE T CO 2 and emphasized the limitations of capnometryin spontaneously breathing anaesthetizedfoals (Geiser & Rohrbach, 1992).Monitoring acid–base statusThe values for HCO 3 and TCO 2 calculated fromthe measured values for pH and PaCO 2 are influencedby both metabolic and respiratory physiologicalfunctions and both values are increased byhypercapnia. The base excess value is obtainedby a calculation that defines the metabolic statusby eliminating deviations of the respiratorycomponent from normal. Zero base excess is neitheracidotic nor alkalotic. Positive base excessdescribes a metabolic alkalosis and a negative baseexcess (base deficit) defines a metabolic acidosis.The metabolic status of a healthy animal is influencedby its diet and, in general, carnivores usuallyhave a mild metabolic acidosis and herbivoresa metabolic alkalosis. An approximate estimate ofseverity of acid–base changes can be obtainedfrom the guideline that a 5 mmol/l change fromnormal is a mild deviation, a 10 mmol/l change is amoderate deviation, and a 15 mmol/l deviation issevere.Chemical determination of TCO 2 in serumor plasma is often used as an estimate of bloodbicarbonate concentration and acid–base statusof patients when blood gas analysis is unavailable.However, the values obtained using autoanalysersmay be significantly different from thatobtained by calculation from pH and PCO 2 . Errorsarise from differences in handling the samples,such as exposure to air, underfilling of bloodcollection tubes, delay in analysis, and changingreagents. A combination of these factorsmay result in lowering the TCO 2 by as much as5.3 mmol/l in canine blood and 4.6 mmol/l infeline blood. This degree of inaccuracy mightresult in erroneous assumptions and affect clinicaldecisions.Acid–base evaluation has always used the VanSlyke technique as the ‘gold standard’ measurementbut more recently a very similar approachhas been available in the form of a simple kit,intended for use with serum (the ‘Harleco’ system),which, when correctly used, is capable ofhigh precision by clinical standards, allowingTCO 2 status to be determined with reasonable

PATIENT MONITORING AND CLINICAL MEASUREMENT 55confidence from samples of venous whole blood(Groutides & Michell, 1988).Monitoring body temperatureIn the normal animal, body heat is unevenlydistributed with the core temperature being 2–4° Chigher than the peripheral. General anaesthesiainhibits vasoconstriction, allowing generalizedredistribution of body heat. An additional decreasein body temperature occurs as heat is lost tothe environment by exposure to cold operatingroom conditions, skin preparation with cold solutions,and abdominal surgical exposure. Furthermore,anaesthetics inhibit thermoregulation,vasoconstriction, and shivering, thereby decreasingthe thresholds for cold responses. Administrationof unwarmed iv. fluid contributessubstantially to the decrease in body temperature.HypothermiaTABLE 2.6 Adverse effects of perianaesthetichypothermiaImpaired cardiovascular functionHypoventilationDecreased metabolism and detoxification ofanaesthetic drugsWeakness during recovery from anaesthesiaDecreased resistance to infectionIncreased incidence of surgical wound infectionIncreased postoperative protein catabolismHypothermia, (35 ° C; 96 ° F), may develop in animalsanaesthetized in a cool environment. Adecrease in temperature of 1–3 ° C below normalhas been demonstrated to provide substantial protectionagainst cerebral ischaemia and hypoxaemiain anaesthetised dogs (Wass et al., 1995).However, life-threatening cardiovascular depressionmay develop when the temperature decreasesbelow 32.8 ° C (91 ° F). Perioperative hypothermiais associated with several other significant adverseeffects (Table 2.6) (Carli et al., 1991; Sheffield et al.,1994; Kurz et al., 1996).Rectal or oesophageal temperature should bemonitored at regular intervals during inhalationanaesthesia, during protracted total intravenousanaesthesia, and during recovery from anaesthesia.Small animals can be insulated from a coolenvironment by a variety of methods, includingplastic covered foam pads and hot water circulatingpads to lie on, and wrapping of extremitieswith towels or plastic insulation. Heat loss fromthe respiratory tract may be minimized by ensuringthat the inspired air remains warm and humidified.This can be accomplished by employingrebreathing circuits and low flow administration,or by attachment of a humidifier to the endotrachealconnexion of the anaesthetic circuit. Heatloss in small cats and dogs is effectively limited byinsertion of a low-volume passive humidifier (e.g.Humid-Vent®, Gibeck) between the endotrachealtube and the anaesthetic circuit. The water vapourin exhaled gases condenses on the humidifier sothat the inhaled air is moistened and warmed.Fluids to be administered iv. should be warm,either in the bag or bottle by storage in an incubatoror at the time of administration by attaching awarming block to the administration line. Activeskin warming of the limbs may be the most effectivemethod of preventing heat loss (Cabell et al.,1997). This can be accomplished by application ofhot water or hot air circulating devices, or warmedtowels and gel-filled packs.Special care should be taken to avoid skinsloughing from burns caused by application ofdevices that are too hot. Electrical heating padsand packs heated in a microwave oven are frequentlyto blame for tissue damage. It should alsobe remembered that warming devices placed overthe site of an intramuscular injection, or an opioidfilledpatch applied to the skin, may alter localblood flow and speed absorption of the drug.HyperthermiaIncreased body temperature is occasionally measuredin anaesthetized animals. Hyperthermiadeveloping in dogs and cats is most often causedby either excessive application of heat in anattempt to prevent hypothermia or by a pyrogenicreaction to a bacterial infection, a contaminant iniv. fluids, or drugs. Other causes of intraoperativehyperthermia are loss of central nervous systemtemperature regulation, thyrotoxicosis, orphaeochromocytoma. Rarely, hyperthermia is amanifestation of the malignant hyperthermia

56 PRINCIPLES AND PROCEDURESsyndrome (MH) which is a life-threatening hypermetaboliccondition triggered by stress and certainanaesthetic agents.Hyperthermia (40.5 ° C; 105 ° F) quite frequentlydevelops in cats during recovery from anaesthesiathat included administration of tiletamine-zolazepam.In these animals, the increase in temperatureis associated with increased muscle activity suchas paddling, uncoordinated movements, or purposefulmovements directed at restraints or bandages.Treatment that is usually effective includesdirecting a flow of air over the cat from a fanplaced outside the cage and providing sedation,for example, butorphanol, 0.2 mg/kg i.m., with orwithout acepromazine, 0.05–0.1 mg/kg i.m.only one of these signs present in a dog that wasmerely overheated.The clinical picture of MH in horses is not clearcut. Abnormal measurements may not be observedfor some time after induction of anaesthesia.Observed signs may be suggestive that the horse isin a light plane of anaesthesia, however, the earliestchanges are usually increased PaCO 2 and E T CO 2 .Heart rates may be mildly elevated and arterialblood pressure is often within the normal range forinhalation anaesthesia (Manley et al., 1983; Klein etal., 1989). Changes in anaesthetic management maypermit the horse to survive anaesthesia but severerhabdomyolysis developing during recovery fromanaesthesia may necessitate euthanasia.Malignant hyperthermiaMalignant hyperthermia (MH) occurs most frequentlyduring anaesthesia of human beings andpigs (McGrath, 1986; Roewer et al., 1995), but hasbeen reported to occur in dogs (O’Brien et al., 1990;Nelson, 1991), cats (Bellah et al., 1989), and horses(Manley et al., 1983; Klein et al., 1989). Clinicalsigns of MH in pigs (p.366) usually include anincrease in temperature, increased respiratory rateand depth, increased E T CO 2 and PaCO 2 , metabolicacidosis, tachycardia, hypertension, and arrhythmias.Purple blotches may be observed in theskin of the abdomen and snout. The soda limecanister on the anaesthesia machine may becomeexcessively hot to touch and the absorbentchanges colour rapidly, reflecting massive carbondioxide production. Rigidity of the jaw and limbmuscles may be observed as the condition progresses.The animal dies unless the condition istreated early.The clinical appearance of dogs developing MHduring anaesthesia may differ from pigs. Tachycardiamay not be a feature, skeletal muscle rigiditymay not occur, and rectal temperature maynot increase until the syndrome is well established(Nelson, 1991). The earliest signs may berelated to increased CO 2 production. These signsinclude an increased respiratory rate and depth,rapid changing of soda lime colour, a hot sodalime canister, and increased E T CO 2 in the absenceof hypoventilation or malfunctioning one-wayvalves. Increased respiratory rate would be theMonitoring urine volumeThe urinary output depends on the renal bloodflow which, in turn, depends on cardiac outputand circulating blood volume, and thus it is a relativelysensitive indicator of the circulatory stateduring anaesthesia. Measurement of urine productionis advisable in animals with severe chronicrenal disease, renal failure, or circulatory failurefrom non-renal causes. The urinary bladder maybe catheterized using aseptic technique beforeanaesthesia or after induction of anaesthesia, andthe catheter connected to a plastic bag for continuouscollection of urine.Urine output of less than 1 ml/kg/hour is inadequateand an indication for treatment. In event ofinadequate urine flow, the anaesthetist should firstcheck that the catheter is not blocked by mucus ora blood clot and that urine is not pooling in thebladder and cannot drain because of the relationshipbetween the catheter tip and positioning ofthe animal.Monitoring blood glucoseClinical signs of hypoglycaemia may not be obviousduring anaesthesia and the condition may gounrecognized. Consequences of hypoglycaemiaare coma, hypotension, or prolonged recoveryfrom anaesthesia with depression, weakness, oreven seizures.Animals at risk for developing hypoglycaemiaduring anaesthesia include paediatric patients,

PATIENT MONITORING AND CLINICAL MEASUREMENT 57diabetics, and animals with hepatic disease, portosystemicshunt, insulinoma, and septicaemia orendotoxaemia. Occasionally, healthy adult sheep,goats, and even horses develop hypoglycaemiawhich manifests as a prolonged or weak recoveryfrom anaesthesia. Routine monitoring of patientsat risk for hypoglycaemia should include measurementof blood glucose at the start and the end ofanaesthesia. Blood glucose can be determined rapidlyusing reagent strips and a glucometer.Animals with low blood glucose concentrationsinitially or those undergoing major or prolongedsurgery, should have their blood glucose monitoredat approximately 1 hour intervals duringanaesthesia.Patients at risk for hypoglycemia should begiven 5% dextrose in water (D5W) as part ofthe intraoperative i.v. fluid therapy. D5W shouldbe infused at a rate of 2–5 ml/kg/hour to maintainblood glucose between 5.5–11.0 mmol/l (100and 200 mg/dl). Balanced electrolyte solutionshould also be infused at the usual rate of5–10ml/kg/hour.Monitoring neuromuscular blockadeThe mechanical response to nerve stimulation (i.e.muscular contraction) may be observed followingthe application of supramaximal single, tetanic or‘train-of-four’ electrical stimuli to a suitableperipheral motor nerve, usually a foot twitch inresponse to stimulation of the peroneal, tibial, orulnar nerves. During general anaesthesia theresponse obtained may be influenced by the anaestheticagents and any neuromuscular blockingdrugs which have been used. Details about neuromuscularblocking drugs and the monitoring techniqueare given in Chapter 7.MONITORING OF EQUIPMENTBefore any anaesthetic is administered all equipmentlikely to be used should be carefully checked.It is essential to ensure that the O 2 supply will beadequate, the circuit is free from leaks and that thecorrect volatile anaesthetic is in the vaporizer. Ifsoda lime is to be used its freshness should bechecked by blowing CO 2 through a small portionand testing to see whether this causes it to get hot.The colour indicator incorporated in many brandsof soda lime cannot be relied upon to indicatefreshness.Interruption in the supply of O 2 to the patient isone of the most serious events which can occur duringanaesthesia and many anaesthesic machinesincorporate warning devices which sound alarmsif the O 2 supply fails. However, when a rebreathingcircuit is being used, the delivery of O 2 in thefresh gas supply does not always ensure that theinspired gases will contain sufficient O 2 to supportlife. Dilution of the O 2 in a rebreathing system isparticularly likely to occur in the early stages ofanaesthesia when denitrogenation of the patient istaking place, or when N 2 O is used with low totalflow rates of fresh gas. Measurement devices areavailable which can be used to demonstrate to theanaesthetist that the patient is receiving an adequateconcentration of O 2 (Fig. 2.5).Inspired and end-tidal concentrations of volatileanaesthetics can be measured by sampling gasesfrom the endotracheal tube connector, as describedearlier in this chapter. In addition to providing informationon the concentration of the volatile anaestheticagent in the patient, the analyser acts as amonitor of the accuracy of output of the vaporizers.REFERENCESBailey, J.E., Dunlop, C.I., Chapman, P.L., et al. (1994)Indirect Doppler ultrasonic measurement of arterialblood pressure results in a large measurement error indorsally recumbent anaesthetised horses. EquineVeterinary Journal 26(1): 70–73.Bellah, J.R., Robertson, S.A, Buergelt, C.D. and McGavinA.D. (1989) Suspected malignant hyperthermia afterhalothane anesthesia in a cat. Veterinary Surgery 18(6):483–488.Bodey, A.R., Young, L.E., Bartram, D.H., Diamond, M.J.and Michell, A.R. (1994) A comparison of directand indirect (oscillometric) measurements of arterialblood pressure in anaesthetised dogs, using tail andlimb cuffs. Research in Veterinary Science 57: 265–269.Branson, K.R., Wagner-Mann, C.C. and Mann, F.A.(1997) Evaluation of an oscillometric blood pressuremonitor on anesthetized cats and the effect of cuffplacement and fur on accuracy. Veterinary Surgery 26,347–353.Cabell, L.W., Perkowski, S.Z., Gregor, T. and Smith, G.K.(1997) The effects of active peripheral skin warmingon perioperative hypothermia in dogs. VeterinarySurgery 26: 79–85.

58 PRINCIPLES AND PROCEDURESCarli, F., Webster J., Pearson M., et al. (1991)Postoperative protein metabolism: effect of nursingelderly patients for 24 h after abdominal surgery in athermoneutral environment. British Journal ofAnaesthesia 66: 292–299.Chaffin, M.K., Mathews, N.S., Cohen, N.D. and Carter,G.K. (1996) Evaluation of pulse oximetry inanaesthetised foals using multiple combinations oftransducer type and transducer attachment site.Equine Veterinary Journal 28(6): 437–445.Clarke, K.W., England, G.C.W. and Goosens, L. (1991)Sedative and cardiovascular effects of romifidine,alone and in combination with butorphanol, in thehorse. Journal of Veterinary Anaesthesia, 18: 25–29.Cribb, P.H. (1988) Capnographic monitoring duringanesthesia with controlled ventilation in the horse.Veterinary Surgery 17(1): 48–52.Ekstrom, P.M., Short, C.E. and Geimer, T.R. (1993)Electroencephalography of detomidine-ketaminehalothaneand detomidine-ketamine-isofluraneanesthetized horses during orthopedic surgery: acomparison. Veterinary Surgery 22(5): 414–418.Fairman, N. (1993) Evaluation of pulse oximetry as acontinuous monitoring technique in critically ill dogsin the small animal intensive care unit. VeterinaryEmergency and Critical Care 2(2): 50–56.Forster, H.V., Bisgard, G.E. and Klein, J.P.(1981) Effect ofperipheral chemoreceptor denervation onacclimatization of goats during hypoxia. Journal ofApplied Physiology 50(2): 392–398.Gallivan, J.G., McDonell, W.N. and Forrest, J.B. (1989)Comparative ventilation and gas exchange in thehorse and cow. Research in Veterinary Science 46(3):331–336.Geddes, L.A., Chaffee, V., Whistler, S.J., Bourland, J.D.and Tacker, W.A. (1977) Indirect mean blood pressurein the anesthetized pony. American Journal of VeterinaryScience 38(12): 2055–2057.Geiser, D.R. and Rohrbach, B.W. 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Introduction to generalanaesthesia: pharmacodynamicsand pharmacokinetics3INTRODUCTIONThe term pharmacodynamics refers to the relationshipbetween drug concentration and its clinical orpharmacological effect, while pharmacokineticsrefers to the mathematical description of the variousprocesses relating to drug movement from thesite of its administration, followed by distributionto the tissues and, finally, elimination from thebody. To paraphrase, pharmacokinetics is ‘whatthe body does to the drug’ whereas pharmacodynamicsis ‘what the drug does to the body’. Theycannot be regarded as separate processes for drugsproduce effects in vivo which alter their own kineticand dynamic profiles, for example by means ofacute haemodynamic effects and increased ordecreased end-organ sensitivity by ‘up’ or ‘down’receptor regulation (Fig. 3.1).In the account of the pharmacokinetics ofinhaled drugs which follows frequent reference ismade to tensions, solubilities and concentrationsof gases in solution. These terms may perhaps bebest explained by considering specific examples.THE TENSIONS OF AGENT DISSOLVED INA LIQUIDThis is the pressure of the agent in the gas withwhich the liquid should be in equilibrium. A liquidand a gas, or two liquids, are in equilibrium if,when separated by a permeable membrane, thereis no exchange between them. The statement that‘the tension of nitrous oxide in the blood is 50.5kPa(380 mmHg)’ means that if a sample of blood wereplaced in an ambient atmosphere containingnitrous oxide at a concentration of 50% v/v (and,therefore according to Dalton’s law, exerting a partialpressure of 50.5 kPa (380 mmHg) there wouldbe no movement of nitrous oxide into or out of theblood. ‘Tension’ is a term used by physiologistsand anaesthetists, while physicists speak of ‘partialpressure’.SOLUBILITY COEFFICIENTS OF GASESAt any given temperature the mass of a gasdissolved in a solution, i.e. its concentrationin the solution, varies directly with its tension(Henry’s law) and is governed by the solubilityof the gas in the particular solvent. Thesolubility of anaesthetics varies widely and, therefore,at any one tension, the quantities of the differentanaesthetics in the solvent are not equal. Thesolubility of anaesthetics in the blood and tissuesare best expressed in terms of their partition, ordistribution, coefficients. For example, the blood–gas partition coefficient of nitrous oxide is 0.47.This means that when blood and alveolar air containingnitrous oxide at a given tension are inequilibrium, there will be 47 parts of nitrousoxide per unit volume (say per litre) of blood forevery 100 parts of nitrous oxide per unitvolume (litre) of alveolar air. In general, the partitioncoefficient of a gas at a stated temperature is61

62 PRINCIPLES AND PROCEDURESDrugActivityAbsorptionRedistribution toinactive tissuesFree drug in plasmaBound to plasma proteinSite fortherapeuticeffectSite(s) forside effectsActivityBiotransformationActivityExcretion of metabolitesExcretionReabsorptionExcretion ofunchanged drugFIG.3.1 Pathways for the uptake,distribution and elimination from the body of an active drug.the ratio, at equilibrium, of the gas’s concentrationon the two sides of a diffusing membrane or interface.Tissue solubility does not necessarily correlatewith blood–gas solubility. The newer volatileagents (e.g. isoflurane, desflurane, sevoflurane)may have a low blood–gas partition coefficient buttheir brain–blood partition coefficient is notnecesssarily lowered to the same extent. Thebrain–blood partition coefficient can be estimatedby dividing the brain–gas with the blood–gas partitioncoefficient. The brain–blood partition coefficientsfor halothane, enflurane, isoflurane anddesflurane calculate to be 1.86, 1.73, 1.67 and 1.27,respectively. Hence desflurane has a more rapiduptake in the brain tissue. For simplicity, in manytheoretical calculations it is often assumed that inthe brain and all other tissues (except fat) gaseshave very nearly the same solubility as they havein blood because their tissue–blood partition coefficientsare sufficiently close in unity.CONCENTRATION OF A GAS INSOLUTIONThe concentration of a gas in solution may beexpressed in a variety of ways including :1. The volume of gas which can be extractedfrom a unit of volume of solution understandard conditions (v/v)2. The weight of dissolved gas per unit volumeof solvent (w/v)3. The molar concentration, i.e. the number ofgram–molecules of gas per litre of solvent. Themolar concentration is the most useful – equimolarsolutions of gases of different molecularweights contain equal concentrations of molecules.This would not be so if their concentrationsin terms of w/v were equal.

INTRODUCTION TO GENERAL ANAESTHESIA 63PHARMACOKINETICS OF INHALEDANAESTHETICSInhaled anaesthetics have a pharmacokinetic profilewhich results in ease in controlling the depth ofanaesthesia as a result of rapid uptake and elimination:a knowledge of this profile can facilitatetheir use in clinical practice. They cannot be introducedinto the brain without at the same timebeing distributed through the entire body, and thisdistribution exerts a controlling influence over therate of the uptake or elimination of the anaestheticby brain tissue. Although with some agents theremay be some metabolism, all the gaseous andvolatile substances used as anaesthetics may beregarded as essentially inert gases as far as uptakeand elimination are concerned.UPTAKE OF INHALED ANAESTHETICSIf some factors are reduced to their simplest possibleterms, and certain assumptions are made, it ispossible to give approximate predictions relatingto inert gas exchange in the body (Bourne, 1964).These predictions are sufficiently realistic for practicalpurposes and serve to illustrate the main principlesinvolved. Once these are understood moreelaborate expositions found elsewhere (Eger, 1974,1990; Mapleson, 1989) should become reasonablyeasy to follow.For simplicity, the physiological variables suchas cardiac output and tidal volume must beassumed to be unaffected by the presence of thegas, and to remain uniform throughout the administration.Allowance cannot be made for alterationsin the tidal volume as administrationproceeds. The blood supply to the grey matter ofthe brain must be assumed to be uniform and thegas to be evenly distributed throughout the greymatter. Finally, although in practice anaestheticsare seldom administered in this way, the anaestheticmust be assumed to be given at a fixedinspired concentration, and, what is more, it mustbe assumed that no rebreathing of gases occurs.The tensions of the gas in the alveolar blood andtissues all tend to move towards inspired tension(Kety, 1951) but a number of processes, each ofwhich proceeds at its own rate, intervene to delaythe eventual saturation of the tissues. The tensionof the gas in the brain follows, with a slight delay,its tension in the alveolar air. Since both the rate ofinduction and recovery from inhalation anaesthesiaare governed by the rate of change of thetension of the anaesthetic in the brain, and this inturn is governed by the rate of change of tension inthe alveoli, the factors which determine the anaesthetictension in the alveoli are obviously of verygreat importance.The rate at which the tension of an anaestheticin the alveolar air approaches its tension in theinspired air depends on the pulmonary ventilation,the uptake of the anaesthetic by the blood andtissues and the inspired concentration. First, bymeans of pulmonary ventilation the gas is inhaled,diluted with functional residual air, and enters thealveoli. This is where diffusion occurs and normallythe alveolar gas equilibrates almost immediatelywith the pulmonary blood which is thendistributed throughout the body. A second diffusionprocess occurs across the capillary membranesof the tissues into the interstitial fluid andfrom there through the cell membranes into thecells themselves. Venous blood leaving the tissuesis in equilibrium with the tissue tension. The bloodfrom the tissues returns to the lungs, still carryingsome of its original content of anaesthetic, and isagain equilibrated with alveolar gas which nowFA as % of FI100'knee'Initial rise(lung wash-in phase)Tail(Tissue saturation phase)00 5 10Time (min)FIG.3.2 Typical alveolar tension curve for an inert gasinhaled at a fixed concentration from a non-rebreathingsystem.

64 PRINCIPLES AND PROCEDUREScontains a slightly higher tension of the anaesthetic.It is in this manner that the alveolar (orarterial) and venous (or tissue) tensions of theanaesthetic in question gradually, and in thatorder, rise towards eventual equilibrium with theinspired tension.As this complex process proceeds, the tensionof the anaesthetic in the alveolar air increases continuously,but not at a uniform rate. Plotted againsttime, alveolar tension rises in a curve that is, ingeneral, the same for every inert gas (Fig. 3.2). Thiscurve tails off and slopes gradually upwards until,after several hours or even days, depending on theanaesthetic in question, complete equilibrium isreached. The steep initial rise represents movementof anaesthetic into the lungs, i.e. the pulmonarywash-in phase. The slowly rising tailrepresents more gradual tissue saturation. Thechange from steep part of the curve to the tailmarks the point at which lung wash-in gives placeto tissue saturation as the most important influence.The tail can be very long if the anaestheticin question has a very high fat/blood partitioncoefficient.BLOOD SOLUBILITY AND ALVEOLARTENSIONThe shape of curve obtained with any given anaestheticdepends on a number of factors. Theseinclude such things as minute volume of respiration;the functional residual capacity of the lungs;the cardiac output and the blood flow to the mainanaesthetic absorbing bulk of the body – musclesand fat. However, one physical property of theanaesthetic itself is considerably more importantthan all of these factors – the solubility of theanaesthetic in the blood. This is the factor whichdetermines the height of the ‘knee’ in the alveolaruptake curve. With anaesthetics of low blood solubilitythe knee is high; with high solubility theknee is low. This may be illustrated by considerationof the hypothetical extremes of solubility.A totally insoluble gas would not diffuse intothe pulmonary blood and would not be carried init away from the lungs. If such a gas were inhaledat a constant inspired tension in a non-rebreathingsystem, its alveolar tension would increase exponentiallyas lung washout proceeded until, after aFA as % of FI1005000 5 10Time (min)FIG.3.3 Alveolar tension curves for a totally insolublegas,A of low solubility,B (nitrous oxide) and a gas ofextremely high solubility,C all breathed at a constantinspired concentration from a non-rebreathing system.very short time, alveolar tension equalled inspiredtension (Fig. 3.3). The curve obtained would be allinitial rise and there would be no tail. Such a gascould not ever be an anaesthetic, since none wouldever reach the brain.A gas of extremely low blood solubility (Fig. 3.3,curve B) would give an almost identical curve. Theloss into the pulmonary blood stream of only aminute amount of the gas contained in the lungs atany moment would bring the tension of the gas inthe blood into equilibrium with that in the alveolarair. The capacity of the blood for such a gas wouldbe extremely small. Likewise, the capacity of theentire body tissue (with the possible exception offat) would be small, since as already pointed out,the tissue–blood partition coefficients of mostanaesthetics are close to unity. If such an agent,even when given at the highest permissible concentrationof 80% with 20% of oxygen only produceda faint depression of the central nervoussystem, it could nevertheless be looked upon as avery active agent because it would be deriving itseffect through the presence in the brain of only aminute trace.At the other hypothetical extreme would be agas of very nearly infinite solubility in blood. Allbut a very small fraction of the gas in the lungs atABC

INTRODUCTION TO GENERAL ANAESTHESIA 65TABLE 3.1 Partition coefficients of some inhalation anaesthesics at 37 °CPartition coefficient Desflurane Isoflurane Sevoflurane Enflurane HalothaneBlood–gas 0.42 1.40 0.60 2.00 1.94Tissue–blood:Brain 1.29 1.57 1.70 2.70 1.94Heart 1.29 1.61 1.78 1.15 1.84Liver 1.31 1.75 1.85 3.70 2.07Muscle 1.02 1.92 3.13 2.20 3.38Fat 27.20 44.90 47.59 83.00 51.10any one moment would dissolve in the pulmonaryblood as soon as the blood arrived at the alveoli.The capacity of the blood and body tissues for sucha gas would be vast. The alveoli tension curve (Fig.3.3, C) would be very flat, with virtually no rapidinitial rise and a very slowly rising tail. Givenenough time for full equilibrium, it might be possibleto achieve very deep anaesthesia by using aminute inspired tension but of course, in one sensethe gas would be a very weak anaesthetic, since itsconcentration in the brain would be enormous.Ranging between these hypothetical extremesof solubility are the gaseous and volatile anaesthetics.Their solubilities in blood and tissuesfor man and some animals (figures taken fromF A /F i1.00.500 10 20 30Minutes of administrationN 2 ODesfluraneIsofluraneHalothaneFIG.3.4 Increase in alveolar tension (FA) towardsinspired tension (FI) during administration at a fixedconcentration in a non-rebreathing system.Effect of bloodsolubility.The curves are not drawn accurately and onlyrepresent approximate,relative curves.various sources but mainly from data sheets) areshown in Table 3.1. The effect of the different solubilitieson the alveolar tension when the agents areadministered at a constant inspired tension areshown in Fig. 3.4.THE TENSION OF ANAESTHETIC AGENTSIN BRAIN TISSUEIn addition to the alveolar tensions, the anaesthetistis also concerned with the tension of anaestheticagents in the grey matter of the brain. In thelungs (unless pathological changes are present)diffusion from the alveolar air to the blood isalmost instantaneous, so that for theoretical purposesthe tension in the arterial blood leaving thelungs can be regarded as equal to the tension in thealveolar air. Only when the body has becomeabsolutely saturated does the arterial tensionequal the tissue tension. During the saturationprocess, and after the administration is stopped,the tissue tension is accurately represented by thetension of the agent in the venous blood leavingthat tissue. This lags behind the arterial tension byan amount which depends mainly upon the bloodsupply to the tissue. Fatty tissues are exceptions tothis rule, for in them the relative solubilities playan important part. In organs with a rich blood supplysuch as the brain and heart, the venous tensionrises quite quickly to the arterial tension. Afterabout 20 minutes (in man) with anaestheticswhose solubility in grey matter is about equal tothat in blood, or perhaps 40 minutes in the case ofagents like halothane which are a little more solublein grey matter, arterial and grey mattertensions, during uptake and during elimination,are almost equal (Fig. 3.3).

66 PRINCIPLES AND PROCEDURESIt follows from these considerations that if a gashas a low blood solubility, any change in its tensionin the alveolar air is quickly reflected in thegrey matter in the brain, whereas if the blood solubilityis high there will be a considerable delaybecause the whole body will act as a very largebuffer. Thus, with an inhalation anaesthetic, thespeed with which induction of anaesthesia can becarried out (when the inspired tension is kept constant)is governed by the solubility of the anaestheticin the blood. Low solubility (e.g. desflurane)favours rapid induction, whereas high blood solubility(methoxyflurane) leads to slow induction.The important point to note here is, of course, thatso far all arguments have been based on theassumption that the inspired concentration ismaintained constant. In fact, alteration of theinspired tension can do much to overcome theslow induction with agents of high blood solubility.For example, if in animals methoxyfluranewere given at concentrations which wouldgive satisfactory anaesthesia afer full equilibration,induction might take many hours. Itwould be a very long time before the animal evenlost consciousness. The difficulty is, of coursein practice, overcome by starting the administrationnot with this concentration, but with onewhich is much higher and which would, if administeredindefinitely, kill the animal. As the desiredlevel of anaesthesia is reached the inspired concentrationis gradually reduced. Even so, inductionwith a very soluble agent such as methoxyfluraneis slow.It is in fact standard practice to hasten inductionof anaesthesia in this way. However, the maximumconcentration which can be administered islimited by the volatility of the anaesthetic, and itspungency. Many anaesthetics are so pungent orirritant that they cannot be inhaled in high concentrations.RECOVERY FROM ANAESTHESIAWhen the administration of the anaesthetic is terminated,its concentration in the inspired air cannotbe reduced (wash-out phase) to below zero.Although the full buffering effect of the body tissueswill not be seen after accelerated inductionsand brief administration (those tissues with a poorblood supply or high tissue–blood partitioncoefficient will then be only very incompletelysaturated), elimination of the more soluble anaestheticswill take time and recovery will be slow.Low blood solubility leads to rapid elimination ofanaesthetics like desflurane and rapid recoveryfrom anaesthesia.At the end of anaesthesia the volume of nitrousoxide eliminated causes the minute volume ofexpiration to exceed the inspired volume and thisoutpouring of nitrous oxide dilutes the alveolarcontent of oxygen. If the animal is breathing roomair, the alveolar oxygen tension can fall to low levels,resulting in a severe reduction in PaO 2 . Thisphenomenon, called ‘diffusion hypoxia‘ can alsohappen if nitrous oxide is cut off during anaesthesia.Theoretically, it can happen with any agent,but it is unlikely to have any ill effects with verysoluble agents such as methoxyflurane, because ofthe small volumes involved and the slow excretionof the agent. The danger is greatest if two insolubleagents (e.g. nitrous oxide and desflurane) areadministered together.SPEED OF UPTAKE AND ELIMINATIONRELATED TO SAFETY OF INHALATIONAGENTSBlood solubility is not only important as a factorinfluencing the speed of induction and recovery. Ithas wider implications; it determines (in an inversemanner) the extent to which tissue tensionskeep pace with alterations in inspired tension andthus it controls the rate at which anaesthesia can bedeepened or lightened. With a very soluble agentsuch as diethyl ether or methoxyflurane no suddenchange in tissue tension is possible; if grossoverdosage is given the anaesthetist has plenty oftime in which to observe the signs of deepeningunconsciousness and to reduce the strength of theinhaled mixture. With an anaesthetic of low bloodsolubility such as desflurane, however, increase intissue tension follows very quickly after anincrease in the inspired tension; anaesthesia maydeepen rapidly and a gross overdose may result. Itis, therefore, very important with the less solubleanaesthetics to consider carefully the factors thatfavour the giving of an overdose, the chief ofwhich must be volatility and potency.

INTRODUCTION TO GENERAL ANAESTHESIA 67VolatilityVolatility governs the potential strength of theinspired mixture for obviously the more volatilethe anaesthetic the greater the risk of its beingadministered at a high concentration. Gaseousanaesthetics and liquid anaesthetics which havelow boiling points are, therefore, potentially dangerous.Because gases are passed through flowmetersthe danger is, in their case, rather less, sincethe anaesthetist has an accuracy of control onlypossible with volatile liquids by the use of special,often expensive vaporizers.PotencyPotency determines the magnitude of a possibleoverdose. With a weak anaesthetic such as nitrousoxide overdose is imposssible; if it were not forlack of oxygen, nitrous oxide could be given at100% concentration without danger. However, aconcentration of 80% of an agent which was fullyeffective when given at a concentration of say 5%would constitute gross overdosage. This is, ofcourse, self-evident, but as has been pointed out byBourne (1964), anaesthetists have in the past paidinsufficient attention to the precise meaning andmeasurement of potency, so that there is muchconfusion. An acceptable definition of potencywould do much to clarify thought relating tosafety of inhalation anaesthetics.UPTAKE AND ELIMINATION OFINHALATION ANAESTHETICS IN CLINICALPRACTICEThe various assumptions made for the purpose oftheoretical or mathematical predictions of inhalationalanaesthetic uptake and elimination cannot bemade in everyday practice. Many of the factorswhich have to be regarded as constant if any mathematicalprediction is to be made, do, in fact, varyconsiderably during the course of anaesthesia.These factors include the tidal volume; the physiologicaldead-space; the functional residual capacity(FRC – that volume of gas in the lungs whichdilutes each single breath of anaesthetic); the thicknessand permeability of the alveolar–capillarymembrane; the cardiac output and pulmonaryblood flow (which may be different, especially inpathological conditions of the lungs); regional variationsin ventilation/perfusion relationships in thelungs; the blood flow through the tissues of thebody; the partition coefficients of the anaestheticbetween the gaseous or vapour state and lungtissue or blood, and between blood and the bodytissues; and the blood flow diffusion coefficient anddiffusion distance for each of the tissues of the body.In addition the anaesthetics themselves maymodify many of the variables as administrationproceeds. For example, most anaesthetics depressbreathing and reduce the cardiac output. Considerationssuch as these indicate only too clearlywhy it is not yet possible to give a complete accountof the uptake and elimination of inhalationanaesthetics as encountered in clinical practice.OTHER FACTORS AFFECTING INHALATIONANAESTHETIC ADMINISTRATION(1) The vaporizerThe output or concentration delivered from avaporizer can be calculated but they are usuallycalibrated manually by the manufacturer. Modernvaporizers are capable of delivering very accurateconcentrations but there are several factors thatcan influence the concentration of a volatile agentin the gas mixture leaving the vaporizer (Fig. 3.5).Older vaporizers were inaccurate at low gasflow rates but most are, today, stable for flows of100 ml to 5000 ml/min. The vapour pressure ofthe volatile anaesthetic in the vaporizing chamberis temperature dependent and most modernvaporizers have temperature compensating mechanismsto correct for this so that output is constantfor a wide temperature range.Vaporizers are usually calibrated for a specificcarrier gas (mostly air or oxygen). When switchingfrom pure oxygen as the carrier gas to a mixture ofnitrous oxide and oxygen, some nitrous oxide dissolvesin the volatile liquid anaesthetic in thevaporizing chamber and thus the total amount ofgas leaving the chamber decreases, causing anoverall decrease in the concentration of the volatileagent. When nitrous oxide is switched off, the dissolvednitrous oxide evaporates from the liquid

68 PRINCIPLES AND PROCEDURESTemperatureVaporizerFresh gas flowDeliverysystemMethod ofcarbon dioxideremovalSecond gas effectConcentration effectAlveolar ventilationLungsSecond gas effectVQ ratioSolubilityCirculationCardiac outputSedativesBrainPerfusionSurgeryEffectAgeFIG.3.5 The concentration cascade between the vaporizer and the brain tissue and some factors which influence it.volatile anaesthetic agent, resulting in an increasedflow through the vaporizing chamber and, therefore,an increase in the delivered concentration.This effect can lead to an error of 20–30% dependingon the fresh gas flow (Lin, 1980).(2) The breathing systemThe fresh gas that flows into the breathing system(circuit) is diluted by the expired alveolar gas,causing a difference between the concentration ofthe inflowing gas and the concentration which isactually inspired. The lower the fresh gas flowrates the greater this difference becomes.Absorption by tubing and any absorbent used toremove carbon dioxide, as well as high anaestheticuptake by the animal, may also increase this difference.At the beginning of anaesthesia soda limebehaves like a ‘molecular sieve’ with saturablecharacteristics. Later a quasi-steady state occursand anaesthetic agents dissove in accordance withtheir partial pressure. Wet soda lime absorbs muchless of volatile anaesthetics than when it is drybecause the ‘molecular sieve’ is occupied by water.A variable amount of the anaesthetic may be absorbedin the tubing of the breathing system. Thereis a large difference between materials and polycarbonis more inert in this respect than teflon.In a circle system the fresh gas utilization willvary widely depending on the arrangement ofthe system components. An arrangement with thespill-off valve between the fresh gas inlet and thelungs will result in a lower fresh gas utilization.Better characteristics with greater utilization arefound where the spill-off valve closes duringinspiration and is as close to the lungs as possible.

INTRODUCTION TO GENERAL ANAESTHESIA 69(3) The lungsDepending on how much fresh gas reaches thelungs and how much anaesthetic is carried awayin the arterialized blood there will be a variableconcentration difference between the inspired andarterial concentrations of the anaesthetic. Theinspired concentration of the agent is the easiestparameter to be changed by the anaesthetist inorder to influence the uptake and elimination ofthe anaesthetic.With higher alveolar ventilation there is a morerapid increase in the alveolar uptake curve. Duringspontaneous ventilation, the animal is to someextent protected against overdosage becausevolatile anaesthetics depress ventilation and consequently,due to negative feed back, the speed ofuptake is reduced. The relative ventilatory depressanteffects of some inhaled agents are: nitrousoxide < halothane (Bahlman et al., 1972) < isoflurane(Fourcade et al., 1971) < enflurane (Calverleyet al., 1978).During spontaneous ventilation the alveolartension of halothane or isoflurane cannot increaseto more than 23 mmHg regardless of the inspiredconcentration because of the resultant ventilatorydepression (Munson et al., 1973).Nitrous oxide, because it can be given in highconcentration, increases alveolar ventilation andthus its own uptake via the concentration effect, inparticular when the animal is hypoventilated andhighly soluble agents are used (Eger, 1963). Forexample, if halothane is used in low concentrations,its uptake is increased as well (second gaseffect) due to the additional inspiratory inflow bythe concentration effect of the nitrous oxide(Epstein et al., 1964).(4) Cardiac outputCardiac output is another major determinant ofinhaled anaesthetic uptake. The higher the cardiacoutput the more anaesthetic agent is removedfrom the alveolar gas and the slower is the rise inalveolar concentration. The volatile anaestheticagents all depress cardiac output and while withspontaneous ventilation a protective negative feedback exists with respect to high concentrations, thereverse is true for the circulation because due toPlasma concentrationEarly distribution phaseLate elimination phaseTimeFIG.3.6 Plasma concentration versus time relationshipfollowing rapid intravenous administration of a drug suchas propofol,illustrating the rapid decline in plasma drugconcentration during the early distributional (α) phaseand the much slower decline in the terminal (β)elimination phase.the depressed circulation less of the agent isremoved from the alveoli so that alveolar concentrationrises more rapidly.PHARMACOKINETICS OFINTRAVENOUS ANAESTHETICSThe pharmacokinetics of the intravenous agents,i.e. the processes by which drug concentrations ateffector sites are achieved, maintained and diminishedafter intravenous injection, is of increasingimportance today because of the use of computermodels to study drug uptake and elimination, andthe use of microprocessors to control anaestheticadministration. For a more detailed account oftheir pharmacokinetics than follows here referenceshould be made to standard textbooks of pharmacology(e.g. Dean, 1987; Pratt & Taylor, 1990).Pharmacokinetic variables commonly reportedfor intravenous or otherwise parenterally administereddrugs are total apparent volume of distribution,total elimination clearance, and eliminationhalf-life .TOTAL APPARENT VOLUME OFDISTRIBUTIONThe total apparent volume of distribution (V d )relates the amount of drug in the body to the plasmaor blood concentration:V d = amount of drug/drug concentration.

70 PRINCIPLES AND PROCEDURESA frequently reported total volume of distributionis the volume of distribution at steady state, V dss ,the total apparent volume a drug would have if itwere in equilibrium with all body tissues. Anothercommonly reported, and usually larger, total volumeof distribution is V dβ which, together withelimination clearance (Cl E ), determines the eliminationhalf-life.In theory, a volume of distribution is measuredby injecting a known quantity of the drug and,after allowing an adequate period of time for it todistribute, determining its concentration (both freeand combined) in the plasma . In practice the equilibriumnecessary is seldom attained becausebefore it is complete the opposing processes ofmetabolism or excretion come into operation.A knowledge of the apparent volume of distributionmakes it possible to calculate the doses to beadministered initially and subsequently to achievedesired concentrations in the blood and tissues.TOTAL ELIMINATION CLEARANCE (Cl E )AND ELIMINATION HALF-LIFE (t 1/2β )Cl E is an independent variable relating the rate ofirreversible drug removal from the body to theplasma or blood concentration:Cl E = rate of elimination/drug concentrationThus, Cl E is the sum of the elimination clearancesof all the organs and tissues of the body, principallythe liver and the kidneys. The eliminationhalf-life, t 1/2β , is a dependent variable and is thetime required for the amount of drug in the bodyto decrease by one-half:t 1/2β = ln2 × V dβ /Cl Eor, t 1/2β = 0.693 × V dβ /Cl E .These pharmacokinetic variables can be useful fordrugs with a rapid onset of action, such as intravenouslyadministered propofol, but they do notprovide a complete description of their pharmacokinetics.The total volume of distribution is notrealized until after extensive drug distribution andredistribution has occurred. Thus, predicted earlydrug concentrations based on the dose and V dsswill be very low. Although elimination clearancebegins from the time the drug arrives at the clearingorgans, the relatively slow decline in drug concentrationsdue to elimination clearance becomes asignificant factor in the relationship of plasma (orblood) concentration with time only after the initalrapid decline due to the distribution and redistributionphase is over (Fig. 3.6).It is now appreciated that the offset of clinicaleffect is not simply a function of half-life. It may beaffected by the rate of equilibration between plasmaand effector site and duration of infusion.Hughes et al. (1992) proposed the use of contextsensitivehalf-time (t 1/2 context ) and defined this asthe time for the plasma conentration to decrease by50% after termination of an i.v. infusion designedto maintain a constant plasma concentration.Context refers to the duration of infusion. Theydemonstrated that context-sensitive half-lines ofcommonly used i.v. anaesthetic agents and opioidscould differ markedly from elimination half-livesand were dependent on duration of infusion.COMPARTMENTAL MODELSDrugs injected into a vein are distributed directlyin the blood stream to the brain and the other tissuesof the body. Those given by the alimentaryroute (by mouth or high into the rectum) must firstbe absorbed into the blood and they then passthrough the liver before reaching the central nervoussystem. Passage through the liver (the ‘firstpass‘) is avoided if the drugs are given via themucous membranes of the nose, the terminal rectum,or sublingually, so that administration of suitabledrugs by these routes renders the effectivedose similar to that needed by the intravenousroute. Elimination of these drugs from the body isnot a reversal of the process of absorption; they arebroken down, mostly in the liver, and are thenexcreted mainly by the kidneys.When a drug is administered by intravenousinjection the onset and duration of its effect dependon the distribution to the tissues, tissue binding andaccess to those tissues where the pharmacologicaleffect takes place, interaction with receptor sites,and elimination by various routes (Fig. 3.1). Sincethe body is composed of innumerable tissue zones,each with a unique blend of perfusion, bindingaffinity, etc. for the drug, quantification of the wholeprocess is nearly impossible unless some gross simplificationscan be made. For any particular drug

INTRODUCTION TO GENERAL ANAESTHESIA 71the body can be thought of as comprising one ormore compartments, each of which can be consideredas a space throughout which the substance isuniformly distributed and has uniform kinetics ofdistribution or transport (Sheppard, 1948).Secondary dispersion of highly lipid-solubledrugs such as the intravenous anasthetic agentsoccurs as they cross cell membranes and the limitingfactor to this process is the rate at which theyare delivered to the cells – the blood flow to the tissues.Thus, organs with a rapid blood flow (e.g.brain, heart, liver, kidney) initially receive a highconcentration of the drug but, with time, this isdepleted as the agent redistributes into moderatelyand slowly perfused tissues (the muscles andfat, respectively). The greater the lipid solubility ofthe drug the more rapid its redistribution but evencharged drugs can be redistributed. Redistributionalso means that repeated doses of the drug canexert prolonged effects due to the gradual passageover an extended period from saturated siteswhere it is inactive, back into the plasma. Plasmaand the organs where blood flow is rapid can betaken to represent one ‘compartment’, while moderatelyand poorly perfused tissues represent secondand third compartments.which has the dimension of rate and will be statedin reciprocal units (t −1 ). From this it follows that agraph of ln(C/C 0 ) against time will yield a straightline, of gradient –k. In practice, very few drugsbehave according to one compartment kinetics,since some initial redistribution from the circulationto other tissues is almost inevitable. Themajority of drugs can be regarded as obeying whatare known as zero order or first order kinetics.A zero order process is one which occurs at a constantrate and is, therefore, independent of thequantity of drug present at the particular sites ofabsorption or removal. A zero order processrequires a large excess of drug available on theentry side (e.g. intravenous infusion) or, on theremoval side, a system of limited capacity.A first order process is considered to be the mostcommon for both drug absorption and elimination.In a first order process the rate of the reactionis exponentially related to the amount of drugavailable. In other words, a constant fraction of thedrug is absorbed or eliminated in constant time.The rate constants ( k ab and k el ) are measurementsof these fractions since they represent the fractionof the drug present which is absorbed or eliminatedin unit time (usually in 1 minute or 1 hour).The one compartment modelWhen drugs behave as if they were distributedinto a single uniform compartment excretion takesplace according to ‘first order‘ kinetics, i.e. in anytime period a constant proportion of the remainingdrug will be eliminated; the elimination rate is proportionalto the concentration. When a drug concentrationdecreases in this constant proportionmanner, the concentration curve can be defined bya simple exponential equation:C/C 0 = e −ktwhere C = drug concentration at time t; C 0 = drugconcentration at time 0 (i.e. immediately after i.v.administration); k = a constant; t = time elapsed;and e = the base of the natural logarithm (2.718).Taking the natural logarithm of both sides of theequation, a linear equation results :ln (C/C 0 ) = –kt or ln (C/C 0 )/t = −k.Thus, the natural logarithm of the proportion bywhich C has decreased to time is a constant (k)Log plasma conc.2.001.000.500.25t 1/200 2 4 6 8Time (hours)FIG.3.7 Simplified diagram of first order eliminationfrom the plasma of an intravenous drug.The plot of logplasma concentration versus time is linear.

72 PRINCIPLES AND PROCEDURESA very simplified example of a first order eliminationis shown in Fig. 3.7 where the natural logarithm(ln) of the plasma concentration of a druggiven by a single intravenous injection is plottedagainst time. Under these conditions a plot of lnplasma concentration versus time is linear. Thetime taken for the plasma concentration to halve(t 1/2 ) is known as the plasma half-life. V d can becalculated for the initial concentration (i.e. that atzero time) and from this, by assuming V d to beconstant over the whole time period (which, inpractice, it seldom is), the clearance from the plasmacan be calculated. A more accurate methodassumes (usually incorrectly) that the clearancefrom the plasma is a constant fraction of the instantaneouslevel, thus:Plasma clearance (C 1 ) =Original doseArea under curve to complete elimination.The area under the curve (AUC) is obtained from agraph of the actual (not log concentration) againsttime. A drug with a high C 1 will have a lower AUCthan one with a lower C 1 given at the same dose. Adrug given to an animal with a reduced C 1 resultingfrom disease will have a higher AUC than thesame drug administered to an animal with a normalC 1 . It follows from this that the diseased animalwill be exposed to a higher drug concentration fora longer period of time and greater and more persistentdrug effects can be produced unless thedose of the drug is reduced.Plasma concentrationTimeMaximumEffective concentrationMinimumFIG.3.8 Intermittent intravenous dosage to maintain aneffective anaesthetic concentration.Single compartmentmodel.What is known as ‘the plateau principle’ applieswhen a drug undergoes zero order absorption andfirst order elimination. Under these conditions itcan be shown that when the concentration of thedrug being administered is changed, the timetaken to reach a steady state (plateau) level isdetermined solely by the reciprocal of k el . Theheight of the plateau reached depends on the concentrationof the drug administered and when thisheight is attained the amount of drug given isreduced to maintain it. Similar principles applywhen a loading dose is followed by subsequentdoses to maintain this level (Fig. 3.8). About 97% ofa drug will be eliminated from the plasma in about5 × t 1/2 (i.e. 50% + 25% + 12.5% + 6.25% + 3.125%).The two compartment modelFrequently, the serial plasma concentrations afterthe intravenous administration of a drug show aninitial rapid decay (the α phase), followed by a lineardecline (the β phase) when plotted on the samesemi-logarithmic axes. The curve of best fit is a biexponentialdecay, which is characteristic of drugconcentration in the central compartment (V 1 ) of atwo compartment system where the drug isassumed to enter V 1 , from which it is also elim-DrugV 1EliminationCDrugV 2 V 2V 3ABDrugV 1 EliminationV 2 V 3V 1EliminationFIG.3.9 A Two compartment model.B Mamillarythree compartment model.C Catenary threecompartment model.In the mamillary three compartmentmodel both V 2 and V 3 exchange with V 1 ,whereas in thecatenary model V 3 is‘deep’ to V 2 and is not connected inany way to V 1 .This catenary model has been proposed forsome drug metabolites and has characteristics of its own.

INTRODUCTION TO GENERAL ANAESTHESIA 73inated. A second peripheral compartment (V 2 )receives drug by redistribution from V 1 but eliminationof the drug does not take place except bytransfer back to V 1 (Fig. 3.9).In the two compartment model the half-life isexpressed as t 1/2β which makes it clear that it islimited to the β (elimination) phase of the decay,but it depends on both elimination and distributionrates so that it cannot be regarded as a directindicator of elimination rate.The multi-compartment modelA three compartment model has been used toexplain a curve of declining drug concentrationwhich does not fit in a conveniently bi-exponentialfashion and better fits a three-exponential equation.However, great care must be exercised whenexpanding the number of terms, since the ‘degreesof freedom’ in the regression equations are progressivelyreduced, thus widening the confidenceinterval for the line. In other words, although amore complex curve may fit measured concentrationpoints better, the probability of it being correctdiminishes. There are two types of three compartmentmodels. In one, the ‘mamillary’ model, bothperipheral compartments (V 2 and V 3 ) connect tothe central compartment (V 1 ). For some drugmetabolites a different, ‘catenary’, model has beenproposed where V 3 is ‘deep’ to V 2 , but is not connectedto V 1 and has quite different characteristics.Rarely can a plasma decay curve be defined soprecisely as to permit justification of more thanthree exponential terms. Moreover, the compartmentscannot be equated with true anatomical volumes.The use of ‘perfusion models’ overcomesmany difficulties to some extent, but these requiremuch more information. The perfusion modeltakes a number of anatomically defined compartmentsand, by consideration of their volumes,blood flow rates through them and tissue/bloodpartition coefficients computes the movement ofdrug between them. Although the distribution ofcardiac output in the anaesthetized horse (Staddonet al., 1979) and the solubility of halothane inequine tissues have been studied (Webb & Weaver,1981) there is little other relevant informationin the veterinary literature. Moreover, thetissue/blood partition coefficients vary widelybecause of the wide range of solubilities in the varioustissues. Thus, the perfusion model is limitedby the number of identifiable tissues or organs forwhich reliable data are available.PRACTICAL METHODS OF DRUG DELIVERYDURING INTRAVENOUS ANAESTHESIAIt is now generally agreed that it is possible toimprove the titration of intravenous drugs byadministering continuous variable rate infusionsrather than by injecting intermittent bolus doses.Continuous infusion is the logical extension of themore traditional incremental bolus dose methodwhich inevitably leads to fluctuations in blood (andhence brain) concentrations that follow each bolusdose (Fig. 3.8). To achieve an effective blood concentrationrapidly, it is necessary to administer a ‘loadingdose’, just as with inhalation anaesthesia it isusually necessary to start with a high inspiredconcentration. Similarly, as with the inhalationanaesthetics, it is necessary to reduce the doseadministered to maintain this effective concentration.In practice, intravenous infusions are generallytitrated on an empirical basis depending on theresponse of the animal to the infusion rate.However, the aim for the future is to predict thedosage requirements from pharmacokinetic data.The smaller the loading dose, the greater the initialmaintenance infusion rate needed because theamount of drug infused must be equal to thatwhich is removed from the brain by both distributionand elimination processes. With time, distributionassumes less importance, and the infusionrate required to maintain any given blood concentrationbecomes solely dependent on the eliminationrate. Thus, the infusion rate needed tomaintain a given concentration in the bodydecreases as a function of the infusion period.Considerations of this nature have led to the establishmentof two or three stages in computer controlledinfusion regimens following a loading doseor inital high infusion rate.Ideally, the anaesthetist would like to know theconcentration of the anaesthetic agent attained andmaintained at its site of effect (i.e. the brain) but, asmay be guessed from the above considerations,this is rarely possible. All that can be said is that

74 PRINCIPLES AND PROCEDURESPropofol conc. (µg/ml)14121086420 20 40 60 80 100 120 140Time (min)FIG.3.10 Blood propofol concentrations (µg/ml) in 6dogs (beagles) after an induction dose of 7mg/kg followedby an infusion of 0.4mg/kg/min,illustrating the tendency ofblood concentrations to rise when the infusion rate iskept constant throughout 120minutes of anaesthesia.the plasma or blood drug concentration is oftenrelated to, and is a valid measure of, the requiredquantity so that t 1/2 is, usually, the paramountdeterminant of dose frequency when intermittentadministration is practised. The main difficultiesin devising suitable computer controlled infusionregimens for the induction and maintenance ofintravenous anaesthesia arise from the variableresponse of individual subjects (Fig. 3.10). Thefuture of computer-controlled infusions foradministering intravenous anaesthetics willdepend on their safety, reliability, cost-effectivenessand ‘user friendliness’.The clinical anaesthetist may be forgiven for feelingthat the sources of variation are so legion that inthe case of many drugs used in anaesthetic practiceit is better to titrate dose against response rather thanattempt to predict the correct dose on theoreticalgrounds. This is a somewhat regressive pharmacologicapproach to the administration of intravenousagents but, at the moment, it certainly offers a simplermodel for everyday use. Even using this approach,a clear understanding of the ways in whichthe animal’s ‘drug model’ may be modified byphysiological or pathological changes makes itpossible to anticipate variations in drug requirementsand, therefore, titrate with greater skill anddelicacy.REFERENCESBahlman, S.H., Eger, E.I. II, Halsy, M.J., et al. (1972) Thecardiovascular effects of halothane in man duringspontaneous ventilation. Anesthesiology 36(5): 494–502.Bourne, J.G. (1964) Uptake , elimination and potency ofthe inhalational anaesthetics. Anaesthesia 19: 12–32.Calverley, R.K., Smith, N.T., Jones, C.W., Prys-Roberts,C. and Eger, E.I. II (1978) Ventilatory andcardiovascular effects of enflurane anesthesia duringspontaneous ventilation in man. Anesthesia andAnalgesia, 54(6), 610–618.Dean, P.M. (1987) Molecular Foundations of Drug ReceptorInteraction. Cambridge: Cambridge University Press.Eger, E.I. II (1963) Effect of inspired anestheticconcentration on the rate of rise of alveolarconcentration. Anesthesiology 24: 153–157.Eger, E.I. II (1974) Anesthetic Uptake and Action.Baltimore : Williams and Wilkins.Eger, E.I. II (1990) Uptake and distribution. In: Miller,R.D. (ed) Anesthesia, 3rd Ed New York: ChurchillLivingstone, pp 85–104.Epstein, R.M., Rackow, H., Salanitre, E. and Wolf, G.L.(1964) Influence of the concentration effect on theuptake of anesthetic mixtures: the second gas effect.Anesthesiology 25: 364–371.Fourcade, H.E., Stevens, W.C., Larson, C.P. et al. (1971)The ventilatory effects of forane, a new inhaledanesthetic. Anesthesiology 35(1): 26–31.Hughes, M.A., Glass, P.S.A. and Jacobs, J.R. (1992)Context-sensitive half-time in multicompartmentpharmacokinetic models for intravenous anaestheticdrugs. Anesthesiology 76(3): 334–341.Kety, S.S. (1951) The theory and applications of theexchange of inert gas at the lungs and tissues.Pharmacological Reviews (Baltimore) 3: 1–41.Lin, C.Y. (1980) Assessment of vaporizer performance inlow-flow and closed-circuit anesthesia. Anesthesia andAnalgesia 59: 359–366.Mapleson, W.W. (1989) Pharmacokinetics of inhalationalanaesthetics. In: Nunn, Utting and Brown (eds)General Anaesthesia, 5th edn. London: Nunn, Utting &Brown, pp. 44–59.Munson, E.S., Eger, E.I. II and Bowers, D.L. (1973) Effectsof anaesthetic-depressed ventilation and cardiacoutput on anesthetic uptake: a computer nonlinearsimulation. Anesthesiology 38(3): 251–259.Pratt, W.B. and Taylor, P. (1990) Principles of Drug Action:the Basis of Pharmacology, 3rd edn. Edinburgh:Churchill-Livingstone.Sheppard, C.W. (1948) The theory of the study oftransfers within a multi-compartment system. Journalof Applied Physics 19: 70–76.Staddon, G.E., Weaver, B.M.Q. and Webb, A.I. (1979)Distribution of cardiac output in anaesthetized horses.Research in Veterinary Science 27(1): 38–45.Webb, A.I. and Weaver, B.M.Q. (1981) Solubility ofhalothane in equine tissues at 37°C. British Journal ofAnaesthesia 53(5): 479–486.

Principles of sedation, analgesia4and premedicationINTRODUCTIONThere is considerable confusion concerning theterminology applied to sedative, tranquillizingand hypnotic drugs, and no single classification iscompletely satisfactory. However, the followingdefinitions are commonly used and almost universallyrecognized:● A hypnotic is a depressant of the centralnervous system which enables the animal to go tosleep more easily, or a drug used to intensify thedepth of sleep. They are rarely used in veterinarymedicine because the state of sleep, from whichthe animal is easily aroused by minor stimulationsuch as noise, is seldom recognizable.● A sedative is a drug which relieves anxietyand as a result tends to make it easier for thepatient to rest or sleep – in fact they are usuallyassociated with drowsiness. Many drugs fall intoboth the sedative and the hypnotic categories, thedifferentiation usually being related to dose. Theyare best considered as one group, exemplified bychloral hydrate or xylazine where low doses causedrowsiness and higher doses cause sleep.● A tranquillizer (or ataractic) is a drug with apredominant action in relieving anxiety withoutproducing undue sedation. They affect mood orbehaviour but in recent years the terms havebecome unpopular (Tobin & Ballard, 1979) andindeed the classification of tranquillizers as‘major’ and ‘minor’ suggested by the WorldHealth Organization is now rarely used. Instead,in pharmacological texts (Booth, 1988), classificationis based on medical clinical uses of thedrugs. Thus, three categories are recognized:antianxiety drugs (or anxiolytics), antipsychoticdrugs and the classic sedative/hypnotics. Benzodiazepinesare considered to be both anxiolytics andsedative/hypnotics. Drugs now classified as antipsychoticare those previously termed neuroleptics.They reduce psychomotor agitation, curiosity andapparent aggressiveness in animals, exertingtheir effects by blocking dopamine-mediatedresponses in the central nervous system. Overdosecauses marked extrapyramidal symptoms andparkinsonian-type tremor (Lees, 1979, 1979a;Vickers et al., 1984). Drugs of the butyrophenoneand phenothiazine groups are now categorized asantipsychotics. The term ‘tranquillizer’ is stillloosely used in clinical anaesthesia to cover boththe anxiolytics and antipsychotics (Dundee &Wyant, 1989), and will continue to be used inplaces in this and later chapters.The multiplicity of definitions is confusing andunderstanding of the major actions of the drugs ismore important than being able to categorizethem, for with this understanding it is possible toappreciate the limitations of the drugs in use. Forexample, if drugs such as the benzodiazepines areused for premedication they will not quieten theanimal, but may make it more difficult to handleby removing its inhibitions, so that vicious animalsbecome more likely to bite or kick, and evenfriendly animals may become uncontrollable. By75

76 PRINCIPLES AND PROCEDURESreducing nervousness, phenothiazine derivativesmay make an animal more liable to sleep, but willnot make the vicious animal easier to handle, nomatter what dose is given.Effective sedation depends on the careful selectionof the drug appropriate for the procedure, thespecies of animal, its temperament and condition,and must allow for possible side effects. Wheresedation is to control an animal so that it mayundergo surgery under local analgesia, comparativelyhigh doses of drugs may be used, but wheresedation fails to be adequate, resort may have to bemade to drug combinations or to general anaesthesia.Where ‘sedative’ and ‘tranquillizing’ drugs areused for premedication, low doses are usually utilizedand their effect on the subsequent depth andduration of anaesthesia must be taken intoaccount. In all cases it is important that the animal isleft undisturbed for an adequate period of timeafter administration of the sedative because stimulationduring the onset of the drug’s action may preventthe full effect from developing. To sedate ananimal that is in pain a suitable analgesic must beused, possibly in combination with a sedative drug,because most sedative drugs themselves have littleor no analgesic activity and may cause exaggeratedreactions to painful stimulation.During the past two decades major pharmacologicaladvances have been made in the recognitionof specific drug receptor sites and of theactions resulting from their stimulation or blockade.These advances have been followed by synthesisof potent drugs which act as agonists or asantagonists at such sites. Where receptors areinvolved in sedation and anaesthesia, theseadvances have included a better understanding ofthe actions of existing drugs, availability of newerand more potent agonist drugs, and of antagonistsenabling the reversal of some sedative agenteffects.SEDATIONPHENOTHIAZINE DERIVATIVESDrugs of this group are classified as antipsychoticdrugs (or in older terminology ‘neuroleptics’).All have a wide range of central and peripheraleffects, but the degree of activity in differentpharmacological actions varies from one compoundto another. These actions and side effectshave been well reviewed (Tobin & Ballard, 1979;Lees, 1979, 1979a).Being dopamine antagonists, they have calmingand mood-altering (antipsychotic?) effects,and also a powerful antiemetic action, particularlyagainst opioid induced vomiting. The degree ofsedation produced varies markedly betweendrugs. For many uses in medical practice sedationis an unwanted side effect, but in veterinary medicinethe phenothiazine derivatives are used primarilyfor this purpose. In general, they do not haveanalgesic activity, although methotrimeprazine isclaimed to be a powerful analgesic in man. Theirmajor cardiovascular side effects are related totheir ability to block α 1 adrenoceptors, and thushaving an anti-adrenaline effect. This results inmarked arterial hypotension primarily due toperipheral vasodilatation, and a decrease inpacked cell volume caused by splenic dilatation.They exert an antiarrhythmic effect on the heart(Muir et al., 1975; Muir, 1981) which was originallythought to be due to a quinidine action on thecardiac membrane (Lees, 1979, 1979a), but hasmore recently been suggested as being caused by ablocking action on the cardiac α-arrhythmic receptors(Maze et al., 1985; Dresel, 1985). They havea spasmolytic action on the gut although, at leastin horses, gut motility is not reduced (J. Davis,personal communication 1990). However, as theycause relaxation of the cardiac sphincter, in ruminantsthey increase the chance of regurgitationshould an animal become recumbent. They havevarying degrees of antihistamine activity andalso produce a partial cholinergic block. All phenothiazinederivatives cause a fall in body temperaturepartly due to increased heat loss throughdilated cutaneous vessels and partly throughresetting of thermoregulatory mechanisms. Inspite of all their side effects the phenothiazines arewell tolerated by the majority of normovolaemicanimals.Although promethazine is used as an antihistamine,the most commonly used phenothiazinetoday in the UK, North America and Australasia isacepromazine, but other derivatives such as chlorpromazine,promazine and propiopromazine areused in some European and other countries.

SEDATION, ANALGESIA & PREMEDICATION 77AcepromazineAcepromazine is the 2-acetyl derivative of promazineand has the chemical name 2–acetyl-10-(3-dimethylaminopropyl) phenothiazine; it is preparedas the maleate, a yellow crystalline solid.The drug has marked sedative properties, whichare responsible for its popularity in veterinarymedicine. Like all phenothiazine drugs, with lowdoses there are effects on behaviour, and as thedose is increased sedation occurs but the dose–response curve rapidly reaches a plateau afterwhich higher doses do not increase, but onlylengthen sedation, and increase side effects (Tobin& Ballard, 1979). Further increase in doses maycause excitement and extrapyramidal signs. Inmany animals sedation may be achieved with i.m.doses as low as 0.03 mg/kg although the drug hasbeen used safely at ten times this dose when prolongedeffects were required. A calming effect onthe behaviour of excitable animals can be seen atdoses even below 0.03 mg/kg, making acepromazine,particularly, a drug liable to abuse especiallyin the equine sporting field. The length ofaction is prolonged. Clinically obvious sedationlasts 4–6 hours after doses of 0.2 mg/kg, but inhorses Parry and coworkers (1982) considered thatthere were detectable residual effects for 12 hoursafter doses of 0.1 mg/kg, and for 16–24 hours after0.15 mg/kg i.m. Owners of giant breeds of dogoften complain that their animals are sedated forseveral days following acepromazine administration,but scientific substantiation of these reports isnot available.In practice, the dose is chosen in relation to thelength of sedation required and the purpose forwhich it is needed. However, the drug cannot berelied upon to give sedation in all animals; someindividuals fail to become sedated and, in these,other drugs or drug combinations must beemployed. Excitement reactions are rare but havebeen reported following i.v. (Tobin & Ballard, 1979)or i.m. injection of the drug (MacKenzie & Snow,1977). Other central effects of acepromazineinclude hypothermia and a moderate antiemeticeffect. Acepromazine is said to reduce the thresholdat which epileptiform seizures occur but it isclaimed that in man the phenothiazine derivativeshave an anticonvulsant effect. It is difficult to reconcilethese two statements but in veterinary medicineit seems to be generally agreed that acepromazineshould be avoided in animals with ahistory of fits or which are in danger of convulsionsfor any reason (e.g. after myelography).In all species of animal acepromazine causes adose related fall in arterial blood pressure and thisproperty has been particularly well documentedin the horse (Kerr et al., 1972a; Glen, 1973; Muir &Hamlin, 1975; Parry et al., 1982). This property isthought to be mediated through vasodilatationbrought about by peripheral α 1 adrenoceptorblock. In most fit and healthy animals the loweringof blood pressure is well tolerated but in shockedor hypovolaemic animals a precipitous and evenfatal fall in arterial pressure can occur. The effectsof clinical dose rates of acepromazine on heart rateare generally minimal, most investigators havingfound a slight rise (MacKenzie & Snow, 1977; Kerret al., 1972a; Parry et al., 1982) or no change (Muiret al., 1979). However, Popovic et al. (1972) reportedthat in dogs doses of 0.1 mg/kg i.m. acepromazinecaused bradycardia and even sinoatrial arrest, andatrioventricular block has been noted in horses(L.W. Hall, unpublished observations). These differencesin reports could be due to the route ofadministration, dose (0.1 mg/kg is high comparedwith doses usually used in clinical practice), orindividual animal sensitivity. Changes in cardiacoutput appear to be minimal (Maze et al., 1985).Acepromazine has antiarrhythmic effects and protectsagainst adrenaline induced fibrillation (Muiret al., 1981) and this property must be an advantagewhen this drug is used for preanaestheticmedication.Fainting and cardiovascular collapse has beenreported to occur occasionally in all species of animalfollowing the use of even low doses ofacepromazine. In some cases it may have been dueto administration to a hypovolaemic animal but inothers it has not been explained. Some strains ofBoxer dogs are renowned for collapsing after avery small dose of acepromazine given by anyroute, and it has been suggested that this may bedue to orthostatic hypotension or to vasovagalsyncope.Clinical doses have little effect on respirationand although sedated animals may breathe moreslowly the minute volume of respiration is usually

78 PRINCIPLES AND PROCEDURESunchanged (Muir et al., 1975; Tobin & Ballard,1979; Parry et al., 1982).Acepromazine has little antihistamine activitybut has a powerful spasmolytic effect on smoothmuscle including that of the gut. It is metabolized inthe liver and both conjugated and non-conjugatedmetabolites are excreted in the urine. The drugcauses paralysis of the retractor penis muscle andprotrusion of the flaccid penis from the prepuce inbulls and stallions; it was often given to facilitateexamination of the penis. In horses, however,physical damage to the dangling penis may resultin swelling and failure of the organ to return withinthe prepuce when the drug action ceases. Thisevent, which may eventually necessitate amputationof the penis, has been reported as occurring inhorses following the use of several phenothiazinederivatives.Priapism has been reported in stallions followingthe use of acepromazine as part of the neuroleptanalgesicmixture ‘Large Animal Immobilon’(Pearson & Weaver, 1978). In most reports the stallionwas being castrated but priapism has beenencountered in other circumstances, for exampleimmediately after induction of anaesthesia with anintravenous barbiturate in acepromazine premedicatedhorses (Lucke & Sanson, 1972). Currentspeculation is that priapism and flaccid protrusionof the penis is due to acepromazine blockade ofcentral and peripheral adrenergic and dopaminergicreceptors but the therapeutic administration ofcatecholamines and anticholinergics has foundlimited success. However, Wilson et al. (1991) havereported two cases of priapism in adult horseswhere detumescence followed the administrationof 8 mg of benztropine mesylate (a drug used inthe treatment of Parkinson disease) which isbelieved to be a central anticholinergic. It is ofinterest that Edwards and Clarke (unpublishedobservations) have encountered three cases of priapismin horses undergoing surgery for relief ofcolic which had not been given acepromazine.As both priapism and flaccid paralysis withsubsequent physical injury are equally calamitousin valuable breeding stallions the manufacturersspecifically contraindicate the drug in these animals.Members attending a meeting of theAssociation of Veterinary Anaesthetists held inthe UK discussed the use of acepromazine in somedetail and their conclusion was that, despitethe possible side effects involving the equine penis,the drug remained a useful sedative in malehorses. It was, however, recommended that onlyminimal doses of acepromazine should be administered,preferably by i.m. rather than i.v. injection,and in the event of priapism or prolonged prolapseof the flaccid penis, the condition ought to betreated quickly and efficiently (Jones, 1979). Thepenis must be supported to prevent or reduceswelling and the application of ice packs togetherwith massage and manual compression may alsobe of help.In the UK acepromazine is available as 2% and10% solutions for injection, and for oral use in dogsand cats as tablets of 5 and 20 mg. The injectableforms are non-irritant and are effective by i.v., i.m.and s.c. routes. Following i.v. injection sedation isusually obvious within 5 minutes but in some casesthe full effects may not be apparent for 20 minutesand when the drug is used for premedication bythis route at least this period should be allowed toelapse before anaesthetic agents are given. Maximaleffects are seen 30–45 minutes after i.m. ands.c. injection. It has been claimed that absorptionfrom s.c. sites is poor and the fact that, at least insmall animals, it works very well when given s.c.,may indicate that even the minimum recommendeddoses are larger than necessary. Given by theoral route, absorption, and therefore its effects, arevery variable and much higher doses need to beadministered (e.g. 1–3 mg/kg in dogs and cats).Very small doses have been used to treat behaviouralproblems in dogs and horses but the doserequired in any individual case can only be foundby trial and error. Its antiemetic properties make ita useful drug for the prevention of motion sicknessin dogs and cats and its spasmolytic propertieshave led to its use in spasmodic colic in horses.It has been very widely used in all species of animalas a sedative and premedicant, as well as incombination with etorphine as ‘Large AnimalImmobilon’.Parenteral doses of acepromazine for sedativeand premedicant purposes in most domesticanimals are in the range of 0.025 to 0.100 mg/kg,the lower doses being used by the i.v. route.Higher doses of up to 0.2 mg/kg may be usedsafely by i.m. injection. Recommended doses

SEDATION, ANALGESIA & PREMEDICATION 79for specific purposes will be discussed in the -chapters relating to the individual species ofanimal.PropionylpromazinePropionylpromazine, 10-(3-dimethyl aminopropyl)-2-propionylphenothiazine,has beenwidely used on the Continent of Europe and inScandinavia for sedation and premedicationof both small and large animal patients. Itsactions, the sedation it produces and its side effectsare very similar to those of acepromazine. Inhorses it is used in doses of 0.15–0.25 mg/kgand in dogs the dose ranges from 0.2–0.3 mg/kg.It has also been widely used in combinationwith methadone.ChlorpromazineThis compound, 2-chloro-10-(3-dimethylaminopropyl)phenothiazine hydrochloride, was usedextensively in veterinary practice but has largelybeen replaced by acepromazine and propionylpromazine.Its actions and side effects are similar tothose of acepromazine, but it is less potent (dosesof up to 1 mg/kg were used in all species of animal),has a longer duration of action and producesless sedation. It is particularly unreliable in horses,giving rise to what appears to be a state of panicdue the muscle weakness it supposedly causes. Itis still widely used in human medicine for itsantipsychotic actions as in psychotic patients itsweak sedative properties constitute a desirablefeature.PromazineThis is 10-(3-dimethylaminopropyl) phenothiazinehydrochloride and has actions similar tothose of chlorpromazine but is claimed to givebetter sedation with fewer side effects. For premedicationit was administered at doses of up to1mg/kg but it is seldom used today.MethotrimeprazineThis is a typical phenothiazine but it is also apotent analgesic, having a potency about 0.7 timesthat of morphine. In veterinary practice in the UKit has been combined with etorphine as theneuroleptanalgesic mixture ‘Small AnimalImmobilon’.PromethazineThis drug, 10-(2-dimethylaminopropyl) phenothiazinehydrochloride, was probably the firstphenothiazine derivative to be used in veterinaryanaesthesia. Solutions of this drug are irritant to thetissues and when used for premedication should beinjected deeply in a large muscle mass 40–60 minutesbefore anaesthesia. In emergencies the drugcan be given, after dilution with isotonic saline, byvery slow i.v. injection. Rapid i.v. injection causes aprofound fall in arterial blood pressure which maybe fatal in shocked or hypovolaemic animals.Promethazine is used in veterinary medicineprimarily for its potent antihistamine activity; it isemployed for premedication prior to the administrationof anaesthetic drugs which cause histaminerelease.BUTYROPHENONESIn man the butyrophenone group of compoundswere classed as major tranquillizers (neuroleptics)but they can cause very unpleasant side effects,including hallucinations, mental agitation, andeven feelings of aggression. These side effects areoften not obvious to an observer and only becomeknown when a human patient recovers from thedrug and complains, often bitterly, about the experience.The incidence of these side effects is doserelated and increases with increase of dose.Overdose results in dystonic reactions. We do notknow whether the subjective effects produced inanimals are similar to those known to occur inman, but the unpredictable aggressive behaviourshown by some animals when under the influencesuggests they may be.Cardiovascular and respiratory effects of thebutyrophenones are minimal, although slightarterial hypotension may result from α adrenergicblockade. They are potent antiemetics, actingon the chemoemetic trigger zone to prevent druginducedvomiting, such as may be caused by

80 PRINCIPLES AND PROCEDURESopioid analgesics. It is this latter property whichmakes the butyrophenones the drug of choicefor the neuroleptic component of neuroleptanalgesia.From experience of their use in man it seemsdoubtful whether the butyrophenones should everbe used on their own as tranquillizing agents, butin veterinary medicine they have been used in thisway as well as in neuroleptanalgesic combinations.It may be that blocking of central dopaminergicand noradrenergic activity is responsible fortheir ability to suppress evidence of opioidinducedexcitement.AzaperoneAzaperone, 4’-fluoro-4 [4-(2 pyridyl)-1-piperazinyl]butyrophenone, is a drug licenced in theUK for use in pigs where its i.m. administrationproduces a good, dose-related sedative effect up tothe maximum recommended dose for clinical use(4 mg/kg). Pigs may show excitement during thefirst 20 minutes following injection, particularly ifdisturbed during this period. Intravenous administrationof this drug frequently results in a vigorousexcitement phase.Azaperone in clinical doses has minimal effectson respiration, such effect as there is being that ofslight stimulation (Clarke, 1969). Clarke alsoreported a consistent small fall in arterial bloodpressure following the i.m. injection of 0.3–3.5 mg/kg of the drug. The effect is presumablydue to the α adrenergic block common to all butyrophenones.Reductions in cardiac output andheart rate in pigs were reported by MacKenzie andSnow (1977) to be clinically insignificant.Azaperone is widely used both as a sedativeand as a premedicant in pigs. In anaesthesia, givenprior to the use of metomidate, it is a useful premedicant(p.368). It is also sold directly to farmersto be used to sedate pigs before transportation,and to prevent fighting following the mixing ofcalves or pigs in one pen. When azaperone isused as a sedative or premedication for vaginaldelivery of piglets or for caesarian section, thepiglets may appear sleepy for some hours afterdelivery. However, provided they are kept warmthey breathe well and there is usually no problemdue to this sleepiness.In horses i.m. doses of 0.4–0.8 mg/kg can sometimesgive good sedation (Aitken & Sanford, 1972)but some horses develop muscle tremors andsweat profusely (Lees & Serrano, 1976) and, inpractice, azaperone often proves unsatisfactory.Should an excitement reaction be encountered anextremely dangerous situation arises in whichinjury to the horse and/or its handlers could occur(Dodman & Waterman, 1979). Although Dodmanand Waterman suggest that the cause of excitementmay be a reaction to the ataxia produced,the fact that pigs show a similar reaction, coupledwith the known central nervous effect in man,suggests that the excitement is due to a direct effectof the drug. Thus, its use in horses cannot berecommended.DroperidolDroperidol is a potent neuroleptic agent with anaction of 6–8 hours duration. It is an extremelypotent antiemetic and is said to antagonize therespiratory depressant effects of morphine-likecompounds by increasing the sensitivity of the respiratorycentre to carbon dioxide. Although it wasclaimed that extrapyramidal side effects were rare,they are produced by overdosing – but are sometimesdelayed for up to 24 hours after administrationof the drug. Doses of 0.1–0.4mg/kg give usefulsedation in pigs for 2–5 hours. However, in pigsdroperidol has largely been superseded by the lessexpensive azaperone. Its main use was in neuroleptanalgesiatechniques when combined with fentanyl(p.369), but more recently 0.5mg/kg has beenused with 0.3mg/kg midazolam, both given i.m., toproduce dependable sedation.FluanisoneThis is 4’-fluoro-4-[4-(o-methoxy)phenyl]-1-piperazinyl)butyrophenone. It was used for neuroleptanalgesictechniques in many laboratory animals.BENZODIAZEPINESChlordiazepoxide was first introduced in 1955 andsince this time drugs of the benzodiazepine grouphave been widely used in human and veterinarymedicine, although their veterinary applications

SEDATION, ANALGESIA & PREMEDICATION 81appear to have been more limited. In man, drugsof this group are utilized to provide:1. an anti-anxiety action2. sedation and hypnosis3. anticonvulsant effects4. muscle relaxation5. retrograde amnesia.A very wide range of different compounds nowexist which are employed for one or more of theseeffects, these compounds differing primarily inbioavailability, permissible route of administrationand length of action.Benzodiazepine compounds exert their mainsedative effects through depression of the limbicsystem, and their muscle relaxing propertiesthrough inhibition of the internuncial neurones atspinal levels. Their action is thought to be throughstimulation of specific benzodiazepine (BZ) receptors,and there are as many as six variants of BZsites (Doble & Martin, 1992). The ligand interactionswith BZ sites are unusual in that three categoriesof action can be identified. Agents whichincrease γ amino butyric acid (GABA) bindingand also GABA-induced chloride currents, areregarded as agonists. Others reduce both GABAbinding and GABA- induced chloride flux; theyare known as inverse agonists and are believed tobe responsible for anxiety and convulsions as wellas having analeptic properties. A third group, thegenuine antagonists of both agonists and inverseagonists, bind but have no efficacy at the site;flumazanil is the drug of this type.GABA is now well validated as one of the twomajor inhibitory amino acid transmitters in thecentral nervous system, the other being glycine(Bloom, 1996). Glycine performs this inhibitoryfunction in the spinal cord, brain stem and retina,whereas GABA is found in the cerebrum and cerebellum.Two types of GABA receptors are recognizedand both these GABA A and GABA Breceptors are found at pre- and postsynaptic sites.GABA A receptors have at least eight interactingbinding sites (Sieghart, 1992). Benzodiazepinespotentiate the actions of GABA at the GABA Areceptor and they do so by increasing the frequencyof Cl − channel opening. Ligand bindingstudies have shown high affinity binding sites forbenzodiazepines associated with GABA and thereis a reciprocal interaction by which GABA and thebenzodiazepines each increase the binding of theother agent. There is a very good correlationbetween the binding affinities of benzodiazepinesto this site and their clinical potencies and it is,therefore, assumed that this is the site at whichthey produce their main effects. In vitro, sevofluraneat concentrations found in clinical anaesthesiaactivates both GABA A and GABA B mediatedinhibitions in the hippocampus (Hirota & Roth,1997)It is very difficult if not impossible to induceanaesthesia with benzodiazepine drugs in fithealthy animals (Lees, 1979, 1979a), although theydo combine with almost any other central nervousdepressant drug to give anaesthesia. It is in combinationswith such drugs as the opioids that theyare generally employed. Certainly, when used forpremedication at subanaesthetic doses, they domarkedly reduce the dose required of subsequentanaesthetic agents, but when they are used inmany combinations their advantage of causingminimal cardiovascular and respiratory effectsmay be lost (Dundee & Wyant, 1989).Most benzodiazepines have a high oralbioavailability and many can also be given by thei.m. and i.v. routes. Their action when given i.v. isnot within one circulation time; there are markeddifferences between individuals in sensitivity andit may take several minutes for maximal effects tobecome apparent. Metabolism is in the liver and inmany instances metabolites are as active or moreactive than the parent compound; actions thereforetend to be prolonged. In fit animals they donot, on their own, cause sedation and indeed theiranxiolytic properties may result in animals becominguncontrollable – a phenomenon also noted inpeople (Dundee & Wyant, 1989).They are used in combination with other drugsto produce sedation and analgesia for intensivecare and to counteract the convulsant and hallucinatoryproperties of ketamine. In a variety ofanimals benzodiazepines have the property of stimulatingappetite (Van Miet et al., 1989). Diazepamhas been particularly widely used for this in catsshowing anorexia following illness and doses ofup to 1 mg/kg have been claimed to be successfulin restoring normal feeding habits. However, indebilitated cats i.v. doses of 0.05–0.1 mg/kg are

82 PRINCIPLES AND PROCEDURESusually adequate and doses of 0.4 mg/kg shouldnot be exceeded if deep sedation is not to result.Of the available benzodiazepine drugs, diazepam,midazolam, climazolam and zolazepamhave been most utilized in veterinary anaesthesia.DiazepamDiazepam is probably the most widely used of thebenzodiazepines. It is, like all other compounds ofthis group, insoluble in water and solutions forinjections contain solvents such as propylene glycol,ethanol, and sodium benzoate in benzoic acid.Intravenous injection may give rise to thrombophlebitisand this is thought to be due to the solventsrather than to diazepam itself. An emulsionspecially prepared for i.v. injection is claimed to benon-irritant to veins, but the bioavailability of thispreparation is reduced compared with that ofother formulations. Because of the problems of solubilitydiazepam should not be diluted with wateror mixed with solutions of other drugs.The effects of diazepam in domestic animals arenot well documented. A rise in plasma concentration,coupled with a return of clinical effects, occurs6–8 hours after administration and is thought tobe due to enterohepatic recycling of the drugand/or its metabolites (Dundee & Wyant, 1989).Premedication with diazepam increases the lengthof action of other anaesthetic agents and thedrug is particularly useful prior to ketamineanaesthesia to reduce the hallucinations whichseem to be associated with this dissociative anaestheticagent.The sedative and hypnotic effects of diazepamappear to be minimal or absent in fit, healthy dogsand attempts to use it for hypnosis or as an i.v.induction agent have been unsuccessful because,used alone in healthy animals, it often inducesexcitement. At clinical dosage rates diazepam hasno significant effect on the circulation or respiratoryactivity but does produce some muscularrelaxation due to its action at internuncial neurones.It has very low toxicity and large dosesgiven to dogs for prolonged periods do not produceany changes in liver or kidney function.Diazepam has a major role in veterinary practicein the control of convulsions of any origin.Averill (1970) recommends that dogs in statusepilepticus should be given 5 mg by slow i.v. injection,followed if necessary by a further 5 mg, andmore recently doses of 10–35 mg have been recommendedfor this purpose. In dogs and cats thedrug has been used both for premedication as apreventative measure and postoperatively to controlconvulsions caused by radiographic techniquesinvolving the introduction of contrastmedia into the spinal canal. Convulsions of toxicorigin in cats have also been treated successfullywith the drug.The use of diazepam as a premedicant, sedativeand tranquillizer is less well documented. Oraldoses of up to 5 mg per day have been used in dogsto control behavioural problems without producingunwanted sedation. It has been used for premedicationprior to the use of ketamine in dogsand horses (Short, 1981, 1981a), and during anaesthesiato abolish ketamine-induced convulsions incats (Reid & Frank, 1972). In the postoperativeperiod, provided pain has been relieved by theappropriate use of analgesic agents, diazepammay be given i.v. in doses of up to 1 mg/kg/hourto control restlessness and facilitate the carryingout of necessary nursing.Diazepam alone has not been widely used inlarge animals and in horses its muscle relaxingproperties may be associated with induced panic(Muir et al., 1982; Rehm & Schatzmann, 1984). Itmay, however, be used as part of a protocol of generalanaesthesia.MidazolamMidazolam, (8-chloro-6 (2-flurophenol)-1–methyl-4H imidazo (1,5-a) (1,4)) benzodiazepine is awater soluble compound yielding a solution witha pH of 3.5. Above pH values of 4.0 the chemicalconfiguration of the molecule changes so that itbecomes lipid soluble. The aqueous solution is notpainful on i.v. injection and does not cause thrombophlebitis.It is metabolized in the liver and inman its half-life is considerably shorter than that ofdiazepam thus it is less cumulative and recovery ismore rapid. These properties have led to its beingused for i.v. sedation and ‘induction of anaesthesia’.Like most benzodiazepines it has minimalrespiratory and cardiovascular effects and incombination with opioids has been widely used

SEDATION, ANALGESIA & PREMEDICATION 83in man for cardiac surgery (Dundee & Wyant,1989).Although literature relating to its use is sparse,midazolam has been used fairly extensively insmall animal patients, especially with ketamine incats (Chambers & Dobson, 1989). The combinationof midazolam (0.25 mg/kg) and metaclopramide(3.3 mg/kg) will produce good sedation in pigseven though neither drug on its own will producesedation in these animals. Again in pigs, midazolam(0.3 mg/kg) has been used by i.m. injectionwith droperidol (0.5 mg/kg) to produce excellentsedation.is now being widely employed to reverse midazolamsedation in ‘day case’ patients.Flumazenil has been reported to reversediazepam or climazolam sedation in sheep andcattle (Rhem & Schatzmann, 1984) and has alsobeen used in combination with naloxone to reverseclimazolam/fentanyl combination anaesthesia(Erhardt et al., 1986). Although to date the veterinaryuse of flumazenil has been limited (Grosset al., 1992; Tranquilli et al., 1992) there is no reasonwhy it should not be employed in any situationwhere it may become necessary to reverse theeffects of a benzodiazepine drug.ClimazolamClimazolam is a potent benzodiazepine which, followingi.v. administration, has a very rapid onsetof effect. It has been used in a wide variety of animalsincluding cattle, sheep, horses and dogs(Rehm & Schatzmann, 1984; Erhardt et al., 1986;Komar & Mouallem, 1988). In cattle, 5mg/kg orallycause sedation and ataxia but much lower dosesby the i.v. or i.m. routes give useful sedation.Horses, however, panic (presumably from the feelingof muscle weakness) and the drug is contraindicatedon its own for these animals, althoughit is useful in anaesthetic combinations, being particularlyeffective for use with ketamine (Rehm &Schatzmann, 1984). Climazolam (1.0–1.5 mg/kg)has also been used in combination with fentanyl(5–15 µg/kg) for anaesthesia in the dog (Erhardtet al., 1986).ZolazepamThis drug is claimed to have marked hypnoticeffects in man. It is now being used in animalscombined, in a fixed ratio, with the dissociativeagent, tiletamine (Rehm & Schatzmann, 1984).This combination (‘Telazol’, Parke Davis), producesrespiratory depression and periods ofexcitement occur during recovery.Flumazenil (benzodiazepine antagonist)Originally developed for the treatment of overdosein man, flumazenil is a potent and specificbenzodiazepine antagonist and in medical practiceα 2 ADRENOCEPTOR AGONISTSXylazine has been used as a sedative in animalssince 1968 (Sagner et al., 1968, 1968a) but at thattime the mechanisms of its complex actions andside effects were not understood. When it wasdescribed as ‘both excitatory and inhibitory ofadrenergic and cholinergic neurones’ (Kronberg etal., 1966) this statement appeared more than a littleconfusing. A similar drug, clonidine, was originallyused in man for its powers of peripheral vasoconstrictionbut later became (and still is) used asan antihypertensive (Schmidtt, 1977).These actions and the correctness of the abovedescription only became explicable when Langer(1974) suggested the existence of receptor sites situatedpresynaptically on the noradrenergic neuroneswhich, when stimulated by noradrenaline,inhibited the further release of this transmitter,thus forming a negative feedback mechanism.Langer suggested further that these presynapticinhibitory receptors differed from the previouslyrecognized α adrenoceptors and should thereforebe termed α 2 adrenoceptors. There is now convincingevidence for the presence of postsynaptic andpresynaptic α 2 adrenoceptors in both central andperipheral sites. The distinction between α 1 , andα 2 adrenoceptors is made on sensitivity to specificagonist and antagonists. Adrenaline and noradrenalinestimulate both types. For α 1 adrenoceptors,phenylephrine and methoxamine areconsidered to be fairly specific agonists and prazosinto be a specific antagonist. Classically, forpharmacological tests clonidine is considered aspecific α 2 adrenoceptor agonist and yohimbine

84 PRINCIPLES AND PROCEDURESand idazoxan antagonists. However, very fewdrugs are absolutely specific in their actions andthe vast majority can only be described as showingselectivity, thus at higher doses the alternative αreceptors may also be stimulated or blocked, a factorpossibly explaining some of the side effects andaberrant reactions occasionally seen with theirclinical use.Characteristic adrenergic responses are predicatedby the structure of the α 2 adrenoceptorswhich is similar to many other neurotransmitterreceptors including the other adrenergic (α 1 , β),muscarinic, opioid and dopamine receptors. Eachof these receptors consists of a single polypeptidechain which meanders back and forth through thecell membrane. The intramembranous portion ofeach adrenergic receptor is hydrophobic and allare similar in structure; from this it can be inferredthat they are the site which recognizes noradrenaline,the common neurotransmitter for each of theadrenergic receptors. By way of contrast, the cytoplasmicadrenergic receptor proteins show muchdifference in structure and especially in their ‘contactregions’ for the many guanine nucleotidebinding proteins (G proteins). At least four differentG proteins couple to the α 2 adrenoceptors.Moreover, biological molecular probes haveshown that at least three different α 2 isoreceptorsexist (Bylund, 1988). These are defined by the locationof the gene for the receptor on the chromosome,being either α 2 c 2, α 2 c 4 , or α 2 c 10 . It is alsopossible to divide the α 2 adrenoceptors at the levelof intracellular second messenger systems. Forexample, the postsynaptic α 2 adrenoceptors invascular smooth muscle and the presynaptic α 2adrenoceptors on peripheral sympathetic nerveendings utilize different transduction mechanisms(Nichols et al., 1988). Finally it is now recognizedthat there are species differences in the location,distribution and type of α 2 receptors.As the presynaptic α 2 adrenoceptors inhibitnoradrenaline release, it might be expected thatthe action of agonists would be the opposite ofthe classic effects of sympathetic stimulation.However, where postsynaptic α 2 adrenoceptorsexist they often exert a stimulating action similarto that exerted by α 1 adrenoceptors at the samesite. The major central and peripheral actions mostrelevant to anaesthetic practice of stimulation ofTABLE 4.1 Results of α 2 adrenoceptorstimulationCNS Sedation,analgesia,hypotension,bradycardiaCVS Peripheral vasoconstriction → initialhypertension. Central bradycardia andvasomotor depression → hypotensionGut Relaxation,decreased motilitySalivation DecreasedGastric ReducedsecretionUterus StimulationHormones Reduced release of insulin,renin andantidiuretic hormone (ADH)Eyes Mydriasis,decreased intraocularpressurePlatelets AggregationAfter Livingstone,Nolan & Waterman (1986)the α 2 adrenoceptors are summarized in Table 4.1and the clinical effects seen with drugs which areagonist at this site are the result of the balance ofthese actions.Clinical actions of α 2 adrenoceptor agonistdrugsIn recent years many new potent and highly selectiveα 2 adrenoceptor agonists have been developedfor both medical and veterinary use. In veterinarypractice the major drugs used are xylazine,detomidine, medetomidine and romifidine;clonidine, although primarily used in medicalpractice, has also been studied in animals in somedetail.The major actions and side effects of all thesedrugs are similar, although there may be differencesin length of action and in the extent and significanceof some of the side effects seen. There arevariations between the drugs in their specificityfor α 2 and α 1 receptors and this explains some ofthe differences in observed clinical effects. There isalso marked variation in species sensitivity to theiractions. For example, cattle are approximately10 times more sensitive to xylazine than horses ordogs, but are equally sensitive to medetomidine asdogs, and equally or less sensitive to detomidinethan horses. Pigs appear very resistant to all thedrugs so far tested. Generalized comparisons of

SEDATION, ANALGESIA & PREMEDICATION 85their potency are meaningless except in the contextof a stated species of animal.The α 2 adrenoceptor agonist drugs are used primarilyfor their central effect of profound sedation(even of hypnosis in some species of animal) butthey also give analgesia through both spinal andcentral actions even in subsedative doses (Vainio etal., 1986; Nolan et al., 1986; Scheinin & Macdonald,1989). This is not surprising because α 2 adrenoceptorsand opioid receptors share similar regions ofthe brain and even some of the same neurones.Binding of either α 2 adrenergic or µ opioid receptoragonists results in activation of the same transductionsystems (the membrane associated Gproteins).The major side effects of α 2 adrenoceptor agonistsare on the cardiovascular system. Althoughthe majority of investigations have been into theactions of xylazine, the evidence to date with thenewer compounds suggests that their actions are,in the main, similar. In all species there is markedbradycardia due to central stimulation and mediatedthrough the vagus nerves. The effects on arterialblood pressure depend on the relative effectsof the central and peripheral stimulation. There isoften an initial hypertensive phase, the extent andduration of which depend on the particular drug,its dose, route of administration, and the species ofanimal concerned, followed by a more prolongedperiod of arterial hypotension, again dependenton the drug and the species of animal. Cardiac outputfalls (but the drugs seem to have little directaction on the myocardium) and the circulationappears to be slowed. The exact state of the peripheralcirculation is more complicated and dosedependent. During the early phase of arterialhypertension with bradycardia, peripheral resistanceis increased, presumably through shut downof blood vessels. How long this poor peripheralperfusion lasts is difficult to ascertain and probablydepends on the species of animal, the drugand the dose used, because in the hypotensivephase peripheral resistance is said to be reduced.The bradycardia, which can be severe, hasgiven rise to much discussion. Many authoritieshave recommended medication with anticholinergicsprior to sedation with these drugs to preventthe fall in heart rate but recent evidence hasthrown doubt on the soundness of this advice. Tobe effective the anticholinergic must be given anadequate time prior to the α 2 adrenoceptor agonist;arrhythmias or tachycardia often result andthe hypertensive phase of the agonist’s action maybe enhanced in the absence of bradycardia. In catsit has been shown that anticholinergics furtherdecrease cardiac output, presumably due to theresulting tachycardia preventing adequate fillingof the heart during diastole (Dunkle et al., 1986),but this does not necessarily apply in larger animals.Work involving continuous recording of theECG has shown the pulse rates of normal sleepingdogs (Hall et al., 1991) and horses (Hall, unpublisheddata) to drop to values similar to those seenin animals sedated by α 2 adrenoceptor agonists.The bradycardia in the sedated animal can be overriddenby toxaemia or by the administration ofsome anaesthetics. Thus, the use of anticholinergicsremains controversial and more study of thepossible combinations is necessary before aninformed judgement of their use can be made.The question of the possible direct effects of α 2adrenoceptor agonists on the myocardium is alsoan open one. There have been reports of animalswhich were in a very excited state at the time ofxylazine administration suffering sudden cardiacarrest and the suggestion has been made that thisdrug might sensitize the heart to adrenalineinduced arrhythmias. Indeed Muir and Piper(1977) showed this to be the case in halothaneanaesthetized dogs but failed to show the sameeffect in horses. It must be noted here that pharmacologicalstudies have failed to demonstrate α 2adrenoceptors in the heart but their presence in thecoronary vessels has been established.Respiratory effects appear to differ betweenspecies of animal. Although with doses whichcause deep sedation in dogs, cats and horses,respiratory rates may be reduced, there is noserious fall in PaO 2 (Hsu, 1985; Dunkle et al., 1986).In ruminants tachypnoea may occur, breathingappears to require a considerable effort and thePaO 2 shows desaturation of the haemoglobin(DeMoor & Desmet, 1971; Raptopoulos et al.,1985; Nolan et al., 1986). This hypoxaemia does notseem to be due to changes in blood pressure or inventilation and, indeed, has been shown to occurfollowing clonidine injection in anaesthetizedartificially ventilated sheep (Eisenach, 1988). Thus,

86 PRINCIPLES AND PROCEDURESintrapulmonary mechanisms have been postulatedas the cause, hypoxaemia being accompaniedby a marked increase in intrapulmonary shunt.Xylazine causes a marked increase in airwayresistance in sheep (Nolan & Waterman, 1985) butnot in cattle (Watney, 1986).All α 2 adrenoceptor agonist drugs cause anincrease in urination, thought to be through inhibitionof ADH release, but when high doses areused, diuresis is possibly assisted by hyperglycaemia.Gut motility ceases almost completely.These side effects must be taken into account whenthese drugs are used to facilitate investigationssuch as barium meals and glucose tolerance tests.Another important side effect of α 2 adrenoceptoragonists is that many (but not all) cause significantuterine stimulation and their administration is,therefore, contraindicated in very early or latepregnancy for they may induce abortion.In doses which produce clinical sedation mostof these drugs cause hypothermia but the mechanismby which this is produced appears to differbetween drugs and species of animal. Xylazineinduced hypothermia has been shown to be antagonizedby idazoxan whilst clonidine inducedhypothermia is intensified by this antagonist(Livingstone et al., 1984). In rats, low doses of detomidinecause hypothermia which can be reversedby yohimbine (Virtanen, 1986) but higher dosescause hyperthermia probably due to an α 1 adrenoceptor-stimulatingaction.When α 2 adrenoceptor agonists are used forpremedication they greatly reduce the doserequirements of inhalation anaesthetics (Virtanen,1986) or intravenous agents. They also combinewith opioids to produce deep sedation or evenanaesthesia.XylazineXylazine, 2-(2,6-dimethylphenylamino)-4H-5,5dihydro-1,3-thiazine, was enthusiastically receivedas a sedative and over the past 20 years ithas maintained its popularity as a generally reliablesedative and premedicant in a wide range ofanimal species (Clarke & Hall, 1969). The drug is atypical α 2 adrenoceptor agonist and exerts itseffects accordingly. However, there are markedvariations in susceptibility to it between the variousspecies of domestic animals. Horses, dogs andcats require 10 times the dose needed in cattle andeven then the degree of sedation achieved inhorses is considerably less. Pigs are even moreresistant than horses (Sagner et al., 1968, 1968a). Itis possible that lesser variations in sensitivity mayoccur in breeds within a single species and thatthis might contribute to the occasional failure ofthe drug to produce sedation.Xylazine can be given by i.v., i.m. or s.c. injectionalthough the s.c. route is not very reliable.Injections are non-irritant although minor temporaryswellings have been reported at the site of i.m.injection of concentrated solutions in horses.Although never proved by laboratory testing,most users of the drug are satisfied that the potencyof available commercial solutions decreaseswith age, and that this deterioration is enhancedby increased environmental temperature (VanDieten, 1988, personal communication).In horses the drug is usually used in doses thatenable the animal to remain standing (althoughwith marked ataxia), but in ruminants and smallanimals sedation is dose dependent and higherdoses are used which may cause recumbency,unconsciousness and a state close to general anaesthesia.After these high doses sedation is veryprolonged and is accompanied by marked cardiovascularand respiratory depression, i.e. they constituteoverdoses. The sedative effects of xylazineappear to be synergistic with a variety of analgesic,sedative and anaesthetic drugs and such combinationsare much preferable to overdoses of xylazinefor the production of sedation.Although the drug can be a potent analgesic,claims as to the degree of analgesia achieved atclinical dose rates are conflicting. Sedative dosesappear to produce a short period of intense analgesiain horses – there is considerable experimentaland clinical evidence that it produces excellentanalgesia in equine colic (Lowe, 1978). However,others (Clarke & Hall, 1969; Tronicke & Vocke,1970) have found that horses deeply sedated withxylazine may respond violently to manipulationsor even attempts to inject local analgesics. It maybe that such reactions are a response to touchrather than pain as non-painful procedures such ashair clipping or placing a radiographic plate maycause a horse to respond with a well directed kick.

SEDATION, ANALGESIA & PREMEDICATION 87Cattle and small animals do not show this markedresponse to touch. Analgesia is not adequate forminor surgery and in cats Arbeiter et al. (1972)found that even massive doses of xylazine sufficientto cause prolonged unconsciousness wereinadequate to abolish all reaction to painful stimuliin the majority of animals. Thus, despite theundoubted analgesic properties of the drug, in theopinion of the authors where surgery is to be performedlocal analgesia must be used to supplementits effects.The cardiovascular effects of xylazine are typicalof this group of drugs and appear to be similar in allspecies of animal (Clarke & Hall, 1969; Garner etal., 1971; Haskins et al., 1986). An initial rise inarterial blood pressure following its i.v. injection asa bolus is short lived and the pressure then falls to10 to 20% below initial resting levels. The hypertensivephase is not always evident after i.m. injection,possibly because of reduced peak bloodconcentrations of the drug.Cardiac output falls due to bradycardia andheart block is usually observed. The advisability ofusing anticholinergic drugs to counteract bradycardiais disputed (Kerr et al., 1972; Hsu, 1985).Pronounced hypertension associated with thebradycardia can usually be avoided by using minimaldoses and i.m. or slow i.v. injection. Xylazineappears to have little direct effect on the myocardiumbut causes a dose related depression of respiration.Falls in PaO 2 are species specific, beingparticularly severe in ruminants, while the musclerelaxing properties make the drug contraindicatedin animals suffering from upper airwayobstruction.Other side effects of xylazine include: muscletwitching when sedation is deep; sweating inhorses at the time sedation is diminishing; vomitingat the onset of sedation in dogs and cats; hypergylcaemia;decreased intraocular pressure and gutmotility and increased urine production. Xylazinealso causes uterine contractions and should not beused in late pregnancy for it may induce prematurelabour. Increase in uterine tone may contraindicateit in cattle or horses receiving ovumtransplants since this may reduce the chance ofimplantation.Xylazine has proved to be a very safe sedativein a wide variety of animals but some serious reactionshave been reported. There have been reportsof violent excitement or collapse in horses associatedwith its intravenous injection. Some of thesemishaps may have been due to inadvertent intraarterialinjection, but it is probable that a few havebeen genuine drug reactions. Fainting throughextreme bradycardia has been suggested as a possiblecause of collapse, but this is unlikely becausethe greatest bradycardia is coupled with arterialhypertension. Deaths have also been reported incattle and the problems of recumbency in ruminantsmust be increased by the hypoxaemiacaused by α 2 adrenoceptor agonists. The advent ofthe opportunity to limit the duration of recumbencyby the reversal of sedation with drugs suchas atipamezole should increase the safety ofxylazine in these animals. In small animals deathshave mainly resulted from the use of xylazine forpremedication.In most species of animal, xylazine is a usefuldrug for premedication prior to induction ofanaesthesia with one of a wide variety of agents.Its use greatly reduces the dose of anaestheticrequired, and although the reduction can often bepredicted from the degree of sedation achieved itmay still be present in animals which have respondedpoorly to the drug. In heavily sedatedanimals circulation is slowed, the effects of subsequentanaesthetic agents is delayed and overdoseof the anaesthetic may result. Thus, particularcare is needed when this sedative is followed byi.v. agents such as the barbiturates, Saffan orpropofol. Xylazine is particularly useful in combinationwith ketamine for its muscle relaxingproperties help to reduce the rigidity causedby the dissociative agent and for many yearsxylazine/ketamine combinations have proveduseful in a wide range of animal species (Muiret al., 1977; 1978; Butera et al., 1978; Brouwer et al.,1980; Hall & Taylor, 1981; Waterman, 1981).DetomidineDetomidine, 4-(2,3-dimethylphenyl)methyl-1Himidazolehydrochloride, is an imidazolederivative which has been developed as a sedative/analgesicfor animals. It is supplied in multidosebottles at a concentration of 10 mg/ml andmay be given by the i.v. and i.m. routes. It is

88 PRINCIPLES AND PROCEDURESnot effective if given orally, but is when administeredsublingually because it is readily absorbedthrough mucous membranes. In a variety of laboratoryanimals its sedative potency has beenshown to be of a similar order to that of clonidineand approximately 10 times (Virtanen, 1986) thatof xylazine. (These relative potencies are not necessarilythe same in domestic animals for in cattle,unlike xylazine, it is no more potent than it is inhorses).The properties of detomidine are well documentedin Acta Veterinaria Scandinavica, Supplement82/1986 (20 papers). Its analgesic powershave been shown in a number of pain models andit is particularly effective as an analgesic in equinecolic (Virtanen, 1985; Clarke, 1988; Jochle et al.,1989). Cardiovascular changes are typical of an α 2adrenoceptor agonist in that there is a markedbradycardia and following doses of 20 µg/kg arterialblood pressure is elevated for about 15 minutesbut falls significantly below control valueswithin 45 minutes of injection of the drug (Clarke& Taylor, 1987; Sarazan et al., 1989). Higher dosesof the drug are followed by more prolonged arterialhypertension but as yet there have been noinvestigations into whether this is followed byprolonged hypotension. Work to date in horsesshows that arterial pressure during anaesthesiaafter detomidine premedication appears to bedependent on the anaesthetic agents used (Clarke,1988). Like xylazine, detomidine causes a minimalfall in equine PaO 2 (Clarke, 1988), but markedhypoxaemia in sheep (Waterman et al., 1986). Inhorses, other side effects include muscular twitching,sweating, piloerection, hyperglycaemia, amarked diuresis and reduced gut motility. Sideeffects increase in frequency and duration withincreased dose.One difference between xylazine and detomidineappears to be in their effects on the uterus.Whereas xylazine appears to have marked ecboliceffects, detomidine, at i.v. doses of 20 µg/kg, slowselectrical activity in the pregnant bovine uterus,although 40–60 µg/kg causes an increase in electricalactivity (Jedruch & Gajewski, 1986).Detomidine is primarily used as a sedativefor horses. In early work doses between 10 and300 µg/kg were employed, horses remainingstanding after the highest doses, although sedationand side effects (bradycardia, arterial hypertension,ataxia, sweating, piloerection, muscle tremorand diuresis) were unacceptably prolonged.This early work serves to demonstrate the veryhigh therapeutic index of the drug as subsequentclinical experience has shown that i.v. doses of 10to 20 µg/kg give adequate sedation for about anhour with much more limited side effects (Clarke& Taylor, 1987). Its action is prolonged in the presenceof abnormal liver function, even when this isnot clinically apparent (Chambers et al., 1996). Thedrug has also been widely used in horses for premedicationprior to induction of anaesthesia withagents such as ketamine, thiopental and propofol(Taylor & Clarke, 1985; Clarke et al., 1986). A moredetailed description of the effects and uses of detomidinein horses is given in Chapter 11.The doses of detomidine required in cattleappear to be similar to those in horses. Again, earlyexperimental work suggested that high doseswere needed for adequate sedation but subsequenttrials have shown that doses of up to30 µg/kg are satisfactory. In the authors’ experience,doses of 10 µg/kg i.v. produce sedation incattle very similar to that seen in horses, i.e. cattleremain standing but show marked ataxia. Therelative lack of hypnotic effect with detomidinemeans that cattle are more likely to remain standingthan after xylazine and this probably led tothe initial misapprehension that cattle requiredhigher doses. Low doses of detomidine may beused safely in early and late pregnancy in cattle(Chapter 18).MedetomidineThis compound, 4-(1-(2,3-dimethylphenyl) ethyl)-1H-imadazole, is a very potent, efficacious andselective agonist for α 2 adrenoreceptors in the centraland peripheral nervous system (Virtanen et al.,1988). The preparation that has been used in veterinaryanaesthesia is a mixture of two sterioisomersand contains 1 mg/ml of the racaemicmixture. The dextrorotatory isomer, which is usedin man as a premedicant and anxiolytic (Scheininet al., 1987; MacDonald et al., 1988), is the activecomponent.Apart from the required actions of sedation,hypnosis and analgesia (Stenberg et al., 1987)

SEDATION, ANALGESIA & PREMEDICATION 89medetomidine has the usual marked cardiovasculareffects of this group of drugs (bradycardia, arterialhypertension followed by hypotension andreduced cardiac output). Its actions in dogs andcats have been well reviewed by Cullen (1996).In most animals medetomidine slows respiration(Clarke & England, 1989). Nevertheless, atnormal sedative doses in non-ruminant animalsthe PaCO 2 does not rise to an excessive level(Vainio, 1989; Cullen & Reynoldson, 1993) and thereis less depression of the ventilatory response toCO 2 than is commonly seen in anaesthetized animals.However, cyanosis has been reported in upto one third of dogs sedated with medetomidine(Clarke & England, 1989; Vaha-Vahe, 1989; Sap &Hellebrekers, 1993). This cyanosis is not associatedwith a lowered arterial PaO 2 or an oxygen saturationbelow 95% and has been attributed to a slowtissue blood flow with increased oxygen extractionleading to cyanosis from venous desaturation.It has not yet been established whether medetomidineis safe for use in pregnant animals but inbitches the electrical activity of the uterine muscleis depressed at doses of 20 µg/kg, while at higherdoses (40–60 µg/kg) there is an initial increase inthis activity for some 5–7 minutes followed bydepression; pregnant bitches do not abort (Jedruch& Gajewski, 1989). Medetomidine markedlyreduces the MAC of volatile agents given subsequentlyfor anaesthesia and a similar synergismmust be expected with i.v. agents whenevermedetomidine premedication is used.The solution is non-irritant and can be administeredby s.c., i.m. or i.v. injection. Intravenous injectiongives the fastest and most reliable results andvomiting is less common than with other routes ofadministration. Vomiting occurs in 10 to 20% ofdogs and 50 to 65% of cats given i.m. medetomidineand although some sedation may be evidentwithin 5 minutes maximal sedation is not achieveduntil 20 minutes have elapsed. Although medetomidineis ineffective when given by mouth, as it isinactivated by passage through the liver, it is readilyabsorbed through mucous membranes and canbe administered effectively sublingually.Following its administration in the dog, the animalrapidly becomes ataxic then stands quietlywith its head down. Vomiting may occur at thistime, but tends to be of short-lived duration comparedwith that induced by xylazine. Next, thedogs becomes recumbent but even if apparentlyvery deeply sedated it can be made to arise andwalk around in an ataxic manner before resumingrecumbency. Muscle twitching may occur, beingmost marked in most deeply sedated animals. Inthe medium sized dog, maximal sedation isachieved with i.m. doses of 40 µg/kg (or half thesedoses by i.v. injection), higher doses lengtheningthe duration of sedation but up to 80 µg/kg alsocontributing to further analgesia. Smaller animalsappear more resistant to the effects so that it hasbeen suggested that doses should be calculated onthe basis of µg/unit body surface area rather thanon body weight. Sedation is less effective in noisyor disturbing surroundings but, once sedated,dogs are not usually responsive to sound. All theother typical side effects such as vomiting, musculartwitching, hypothermia, decreased gut movementand hyperglycaemia, have been noted(Vainio et al., 1986; Clarke & England, 1989).In cats higher doses (80 to 150 µg/kg i.m.) areneeded to produce sedation. Sedation is usuallyexcellent but the animals are capable of beingaroused. The i.v. use of medetomidine in cats hasapparently not been widely explored.The drug has been widely used in combinationwith other drugs to prolong recumbency. In thedog opioids have proved to be successful (Clarke& England, 1988) but the most popular combinationshave been with ketamine, even 1 to 2 mg/kgof ketamine being adequate to ensure prolongationof recumbency.Medetomidine has been used in sheep andcattle; i.v. doses of 10 to 20 µg/kg causingsedation similar to that seen after 0.1 to 0.2 mg/kgof xylazine (Clarke & England, unpublishedobservations). In wild animals higher dosesare required and the drug has usually beenused in combination with ketamine when administeredby dart gun for immobilization. Indeed,medetomidine/ketamine combinations have beenfound to provide excellent immobilization andrelaxation in a wide range of species of animals,while the ability to reverse the sedation with α 2adrenoceptor antagonists has proved to be particularlyuseful (Jalenka, 1989, 1989a).The drug has also been used in many rodentsand other laboratory animals and there is marked

90 PRINCIPLES AND PROCEDURESvariation in susceptibility to its effects, the guineapig being most resistant. Once again, combinationswith ketamine are more effective than thesedative alone.RomifidineThis drug, developed from clonidine, has typicalα 2 adrenoceptor agonist effects. It has undergoneclinical trials in Germany, Switzerland and the UKas a sedative (Clarke et al., 1991) and premedicant(Young, 1992) for horses. Maximal sedation isachieved with i.v. doses of 80 µg/kg. When comparedin horses given i.v. xylazine (1 mg/kg) ordetomidine (20 µg/kg) it produces less ataxia andthe head is not lowered to the same extent, butresponse to imposed stimuli is reduced to the samedegree by all three drugs. At these doses, the durationof effect is longest with romifidine, the horsesremaining quieter than normal for some considerabletime after obvious sedation has waned.Romifidine produces a marked increase in urineproduction over 90 minutes accompanied by anincrease in sodium and glucose excretion whilecreatinine clearance remains constant (Gasthuyset al., 1996).In dogs, recovery from romifidine is rapid(Michelsen, 1996) but the liver contributes verylittle to its overall clearance from the body (Chism& Rickert, 1996).α 2 ADRENOCEPTOR ANTAGONISTSThe central and peripheral effects of the α 2 adrenoceptoragonists can be reversed by the use ofequally specific antagonists. The antagonists usedinclude yohimbine (Hsu et al., 1989), idazoxan(Docherty et al., 1987; Hsu et al., 1989), tolazoline(Hsu et al., 1987) and atipamezole (Clarke &England, 1988; Kock et al., 1989), the most potentand specific being atipamezole.The ability to awaken xylazine or detomidinesedatedsubjects has proved to be particularly usefulin wild animals where prolonged sedation maybe fatal (Kock et al., 1989), and in domestic ruminants(Thompson et al., 1989) where prolongedrecumbency is again unwelcome. Also, in someclinical situations the α 2 adrenoceptor antagonistsare useful in small animal practice.When using antagonists in the clinical situationit is necessary to consider the pharmacokinetics ofthe drugs involved, because if the antagonist iseliminated faster than the agonist, resedation willoccur; this is most serious in wild animals whichare not under observation and vulnerable to predators.The dose rates of antagonist drugs forreversing sedation will obviously vary with thedose of sedative used and the elapsed time after itsadministration. With all antagonists investigated,higher doses are required to reverse cardiopulmonaryeffects than to reverse sedation (Hsu et al.,1989; Vainio & Vaha-Vahe, 1989). The situation iscomplicated by the fact that there may be speciesdifferences in antagonistic effects and it is, therefore,very difficult to be certain of the exact dose ofantagonist necessary in any particular case. Forthis reason it is important that no side effects occurshould the antagonist be overdosed. Convulsionshave occasionally been reported after yohimbine,idazoxan and atipamezole but in most reports ketamine,which is not influenced by the α 2 adrenoceptorantagonists, was part of the sedativecombination used and may have been the cause ofthis side effect.Of the α 2 adrenoceptor antagonists, yohimbineand atipamazole are the most commonly used inveterinary practice. Numerous studies havedemonstrated the effectiveness of yohimbine inantagonizing α 2 agonist induced sedation andanalgesia in laboratory animals, dogs and cats(Holmberg & Gershon, 1961; Hsu, 1983). Doses of0.1 mg/kg have generally been employed toreverse xylazine sedation in small animals; highdoses have caused excitement in dogs (Paddleford,1988). Yohimbine has sometimes been used incombination with 4-aminopyridine, a drug whichreleases acetylcholine and other neurotransmittersfrom presynaptic nerve endings, but the combinationappears to have no advantages over the use ofthe antagonist alone.Atipamezole has mainly been used to reversemedetomidine sedation in dogs (Clarke &England, 1988; Vainio & Vaha-Vahe, 1989), cats(Virtanen, 1989) and wild animals. Serious relapseinto sedation has not been noted, although followinglow doses of the drug animals have beendescribed as appearing ‘tired’ for some hours.Overdose of atipamezole does not appear to cause

SEDATION, ANALGESIA & PREMEDICATION 91problems in most species of animal, injection intothe unsedated dog (Clarke & England 1988) causingmild muscular tremors but little else andconvulsions have never been noted in the absenceof ketamine. However, although atipamezoleappears to have little effect in unsedated cats, whenused to reverse medetomidine sedation a few catshave been described as being ‘over-reversed’ butovert excitement has not been seen. Atipamezolehas also been shown to be effective in reversingdetomidine sedation in horses, and xylazine sedationin wild animals, sheep and cattle.Tolazoline (Tolazine, Lloyd Laboratories, Iowa)is used in doses of 4 mg/kg to antagonize theeffects of xylazine in horses. The rate of i.v. administrationneeds to be controlled to approximately100 mg/min. It is a mixed α 1 and α 2 adrenergicreceptor antagonist and also has a direct peripheralvasodilator action. Temporary side effects,which usually last not more than 1 to 2 hours,include increases in blood pressure, tachycardia,peripheral vasodilatation and sweating.TAMERIDONETameridone, a purine alkyl piperidine derivative,has undergone extensive clinical and pharmacologicalinvestigations in cattle where i.v. doses of0.05 mg/kg or i.m. doses of 0.1–0.2 mg/kg producegood sedation for 90–120 minutes. Sedationappears to be dose dependent in depth and takeslonger to appear than sedation after xylazineadministration. The drug appears to be equallyeffective in all breeds of cattle but cows at full termundergoing caesarian section appear to be undulysensitive, i.v. doses of 0.03 mg/kg readily causingrecumbency. In the USA tameridone has been triedextensively for the capture and transport of wildruminant animals but the results have been variable– doses and depth of sedation achieved differbetween species of animal.ANALGESIAAlthough an animal may be deemed to be unconsciousduring general anaesthesia and, therefore,incapable of appreciating pain, there is now evidencethat the use of analgesic drugs before and duringgeneral anaesthesia assists in obtaining a smooth,pain-free recovery. All general anesthetics undoubtedlyhave an intrinsic analgesic action but furtheranalgesia can be provided by four main methods:1. Use of local analgesics2. Use of α 2 adrenoceptor agonists3. Use of non-steroidal anti-inflammatorydrugs (NSAIDs)4. Use of opioid drugs.Local analgesics, particularly the long acting groupof drugs, e.g. bupivacaine, used during surgerymay also provide outstanding postoperative analgesia.These drugs are discussed in more detail inChapter 10. α 2 Adrenoceptor agonists, discussedabove, when used parenterally at analgesic doseswill also cause deep sedation (which is not alwaysa disadvantage in the postoperative period) andbradycardia. In man, and increasingly in animals,these α 2 adrenoceptor agonists are now beingadministered epidurally to limit their side effects.With all of these drugs, there is now convincingevidence that they are more effective if administeredbefore pain becomes manifest (Mitchell &Smith, 1989).NON-STEROIDAL ANTI-INFLAMMATORYDRUGS (NSAIDs)These agents act primarily by inhibiting prostaglandinrelease at the site of trauma and by reducinginflammation and swelling – themselves a majorsource of postoperative pain. Details of the verylarge number of NSAIDs, their uses, limitationsand toxicity are beyond the scope of this book butare well reviewed in current standard pharmacologicaltexts. With due care, they can make a mostuseful contribution to postoperative analgesia.SalicylateAcetylsalicylate (‘Aspirin’) was one of the firstNSAIDs used in veterinary medicine and still has aplace, particularly for postoperative pain and discomfortin small animals. It acts as an analgesicboth centrally and peripherally. It is said to causegastric irritation due, in part, to ion trapping (iontrapping occurs when an ion passes through amembrane and encounters a different pH from

92 PRINCIPLES AND PROCEDURESwhich it has difficulty in escaping). By this mechanismthe concentration of aspirin within a cell maycontribute to the gastric irritation because aspirinwhich is absorbed in the stomach at the intracellularpH of approximately 7.4 reverts to the ionizedform which can only slowly cross from the cellsinto the blood plasma (aspirin pK a = 3.4 so that theionized concentration is 10 4 times that of theunionized amount). The so-called ‘soluble’aspirins are certainly solutions at about neutralpH, i.e. when dissolved in water, but precipitate aconsiderable proportion of the drug in the acidmedium of the gastric juice. ‘Buffered’ aspirinpreparations reduce ion trapping by decreasinggastric absorption. In the alkaline medium of thesmall intestine the aqueous solubility of aspirinincreases and although the unionized form of thedrug is present in much lower proportion, most ofthe absorption into the bloodstream occurs due tothe larger absorptive surface and the greater timespent in this part of the gastrointestinal tract.Plasma content is chiefly (due to rapid hydrolysisin blood and liver) in the form of sodium salicylatewhich is heavily protein bound.There is little evidence of clinical harm causedby aspirin irritation of the canine or feline stomachapart from one isolated report of buffered aspirincausing massive gastric haemorrhage in a Greyhound(Shaw et al., 1997). By diminishing plateletaggregation it has a small, clinically insignificant,effect in prolonging blood coagulation.Dogs can quite safely be given 10 mg orally perday and cats 5 mg per day by the same route(Davis & Donnelly, 1968). It may be given preoperatively,or after the first 48 to 72 hourspostoperatively when the most severe postoperativepain has waned.PhenylbutazonePhenylbutazone is a favourite drug of horse ownerswishing to alleviate minor degrees of lamenessas an alternative to euthanasia. Veterinaryanaesthetists may use this drug as an analgesicanti-inflammatory in the treatment of equine postanaestheticrhabdomyolysis in i.v. doses of4mg/kg. In dogs i.v. injections or oral administrationof up to 20 mg/kg (100 and 200 mg tablets areavailable in the UK) are used for the treatment ofpain and may be given daily in divided dosesevery 8 hours for not more than one week.The drug is highly protein bound and shouldnot be administered with other highly proteinbound drugs for this can lead to toxic effects. Itshould not be administered to cats (Christianson,1980) and since in all animals it produces manyside effects which are likely to be severe if theusual therapeutic dose is exceeded many authoritiesconsider this drug to be obsolescent.FlunixinFlunixin in i.v. doses of 1.1 mg/kg is used in horsessuffering from colic for its antiendotoxic and visceralpain relieving properties. Doses should notbe repeated more than twice. Consequently, manyanimals presented for surgical treatment of colicwill have received the drug prior to surgery. Itssafety in pregnant mares has not been demonstrated.The drug in tablet form is also used indogs for the control of postoperative pain andinflammation at a dose of 1 mg/kg for up to threedays. Side effects in dogs include vomiting anddiarrhoea and it should not be administered topregnant bitches. Its pharmacokinetics and pharmacodynamicsin cats have been reported by Leesand Taylor (1991).KetoprofenKetoprofen is used in horses, dogs and cats. It issaid to be approximately 15 times more potentthan phenylbutazone and 30 times more potentthan aspirin. The i.v. dose for horses is 2.2 mg/kg,once daily, in dogs it is 2 mg/kg by the i.v., i.m. ors.c. routes, and in cats (s.c.) 2 mg/kg is given, ineach case for not more than three days.In common with other NSAIDs it is not permittedby the racing authorities of Great Britainand Ireland to be used at the time of racing andketoprofen or its conjugates can be detected inurine for up to 10 days after its administrationceases.CarprofenCarprofen is the latest NSAID to be introducedinto veterinary practice. It does not appear to act

SEDATION, ANALGESIA & PREMEDICATION 93by inhibition of cyclo-oxgenase or lipoxygenase(McKellar et al., 1990) as the earlier NSAIDs do.The side effects of these drugs generally resultfrom inhibition of prostaglandin formation by thismechanism, so carprofen promises to have fewerside effects than the other drugs.In horses carprofen is used as a single i.v. doseof 0.7 mg/kg (1 ml/70 kg) which may be repeatedafter 24 hours or followed with oral therapy for upto five days. In dogs, the drug is given before orimmediately after induction of general anaesthesiain i.v. or s.c. doses of 4 mg/kg for ‘pre-emptiveanalgesia’. Clinical evidence in dogs suggests thatonly a single dose of carprofen is required in thefirst 24 hours perioperatively; if analgesia is neededafter this, half the initial dose may be given fornot more than seven days. Its analgesic activity incats has been described by Lascelles et al., (1995)who found that i.m. pethidine (meperidine) indoses of 10 mg/kg produced significantly betterpostoperative analgesia for up to two hours postoperativelybut from 2 to 20 hours postoperativelythe reverse was true and 4 mg/kg carprofen providedsignificantly better pain relief.OPIOID ANALGESICSOpioids have been used as painkillers in man forat least 2000 years and the refined and processedextracts, morphine and heroin, still have a majorrole as analgesics. There is now a wide range ofboth naturally occurring and synthetic opioids, sothat the clinician has an enormous range of choice.The principal reason for employing opioids is toprovide analgesia but some are used as coughsuppressants. Unfortunately, these drugs have awide range of side effects, the most important ofwhich is probably respiratory depression. Evenmore unfortunately, in man these drugs causeeuphoria and addiction, rendering them liable toabuse and resulting in controls on their use. Abuseis not a feature of their use in veterinary patientsbut they have other undesirable side effects,including the production of nausea and vomiting(in dogs), constipation, pruritis and in somecases dysphoria. Whilst in dogs they invariablycause sedation, in cats and horses higher dosescause excitement, although clinical doses can beused quite safely in these species of animal, beingparticularly unlikely to produce excitement whenpain is present.The use of nalorphine as an antidote to morphinepoisoning in man was first reported in 1951and since then other agents which antagonize theeffects of morphine have been produced. Many ofthese have partial agonist activity, sufficient forthem to be used as analgesics, and often they areless liable to abuse and, therefore, have fewer controlsover their use. Pure antagonists, such asnaloxone, will reverse the effects of morphine atdoses which have no intrinsic activity when givenalone.In recent years the discovery of specific receptorsites of action for the opioids (first suggested byMartin et al., 1976) and the identification in the centralnervous system of endogenous ligands such asencephalins, endorphins and dynorphin which actat these receptors, has led to better understandingof the multiple actions of agonist and partial agonistopioid drugs, as well as providing the possibilityof the development of more specific drugswith fewer side effects. On the basis of response tospecific drugs Martin et al. initially postulated theexistence of three opioid receptors receptors,termed µ, κ and σ.Other multiple receptors have since been postulatedand it is now accepted that the one known asthe δ receptor is of importance. Table 4.2 showsreceptor selectivity of some opioid analgesics.Many authorities now do not consider the σ receptorto be a true opioid receptor. The actionswhich are suggested to occur on activation of theseTABLE 4.2 Receptor selectivity (agonist andantagonist) of some opioid drugsDrug µ receptor κ receptorδ receptorBuprenorphine +++ ? ?Butorphanol ++ ++ −Diprenorphine ++ ++ ++Fentanyl +++ − −Methadone +++ − −Morphine +++ +/− −Naloxone +++ + +Nalbuphine +++ + −Pentazocine ++ + +Pethidine ++ − −Remifentanil +++ − −Sufentanil +++ + +

94 PRINCIPLES AND PROCEDURESvarious receptors have been the subject of verymany reviews and Table 4.3 summarizes, in a verysimplified form, the suggested actions followingstimulation of the receptors as gleaned from thesereviews.The cloning of receptor sites, with the identificationof a large number of variations, has led to are-classification in which the classical receptors arenow termed OP 1 (previously the δ receptor), OP 2 ,(κ) and OP 3 . (µ). However, as this classification isas yet unfamiliar in anaesthetic use, the originalterminology will continue to be used in this book.It is thought that analgesia results primarilyfrom stimulation of the µ and κ receptors whilestimulation of the δ receptors modulates the effectsat the µ receptors.Drugs classified as pure agonists, e.g. morphine,cause analgesia by stimulation of the µ andκ receptors, although they may have actions elsewhere.Naloxone is antagonistic at all receptorswhere it is active. The partial agonist/antagonistdrugs show a range of activity. Some may act asagonists at one type of receptor whilst antagonizingat another; some have partial agonist actions ata single type of receptor, low doses stimulating thereceptor but higher doses antagonizing this effect.Unfortunately, in intact animals, unlike in pharmacologicalpreparations, responses may not be soclear cut. For example, butorphanol is said to haveno µ activity but it induces a ‘walking’ response inTABLE 4.3 Actions suggested to occur onstimulation of opioid receptorsReceptor Suggested actionµ Spinal and supraspinal analgesiaRespiratory depressionEuphoriaNausea and VomitingChanges in gut motilityMiosisAddictionSedationκSupraspinal analgesiaSedationAddiction (mild)MiosisDysphoria and psychomimetic effectsδσanalgesiaDysphoria and psychomimetic effectsMydriasishorses, which is said to be a µ effect (Tobin et al.,1979). Nevertheless, despite discrepancies, aknowledge of the range of activity at differentreceptors is helpful in arriving at an understandingof the actions, side effects and reversibility ofthe wide range of opioids available for clinical use.Increasing the dose of pure agonist drugs increasesanalgesia but, unfortunately, also increasesrespiratory depression. Moreover, all the drugswhich have potent µ agonist activity appear tohave effects which give rise to abuse by humans. Ithas been suggested that there are µ 1 and µ 2 receptors,stimulation of µ 1 resulting in analgesia whilstµ 2 stimulation leads to respiratory depression andabuse. Meptazinol was claimed to be a pure µ 1 agonist(Sanford, 1948) but this drug does not appearto have lived up to early expectations and is nowthought to act also by other mechanisms.Partial agonists have a limit to the analgesiathey can produce, increasing doses sometimesantagonizing the analgesia of lower doses (i.e. thedose–response curve is bell-shaped). However, therespiratory depression produced by the partialagonists is also limited, maximal depression reachinga plateau at high doses. Unfortunately, themaximal respiratory depression produced maystill be of some clinical significance. Partial agonistdrugs are less liable to human abuse, primarilybecause many produce unpleasant dysphoric andhallucinatory effects. Psychomimetic and hallucinatoryeffects have generally been consideredsigns of σ receptor stimulation. Recently, pure κagonists have become available and it was hopedthat these drugs would have the analgesic advantagesof an opioid agonist without causing respiratorydepression or having a major potential forabuse. Regrettably, all the drugs available to datecause unacceptable dysphoria in man and as aresult it is now postulated that some of the actionsattributed to σ receptor stimulation may in fact bea property of κ receptor stimulation. As animalscannot complain of dysphoric or hallucinatoryexperiences it behoves veterinarians to exercisecare when using drugs likely to cause such effects.General actions of opioid agonists in animalsAt least in man, it seems that the euphoric effectsof morphine-like drugs contribute to the analgesia

SEDATION, ANALGESIA & PREMEDICATION 95they produce, patients being unconcerned by anyresidual pain. Whether this is also true in animalscan only remain a speculation. The pure agonistsproduce dose-dependent respiratory depressionbut it must be emphasized that in chest pain lowdoses may improve respiratory activity throughthe analgesic effect. In ambulatory humans, dogsand cats, morphine and some other opioid agonistscause vomiting and as they also produce markeddepression of the cough reflex care must be takento ensure that inhalation of vomit does not occur.Opioid agonists increase the tone of the gut, particularlyof the sphincters, and decrease transit time,causing constipation. Their use is generally contraindicatedfor biliary or ureteric pain as theycause spasm of the bile and ureteric ducts.Cerebrospinal fluid pressure is elevated, so theiruse is also contraindicated in head injuries. Thepure agonist drugs’ effects of causing toleranceand addiction in man results in their being subjectto tight statutory controls.In humans, dogs and rabbits, opioid agoniststend to cause central nervous depression whilst incats and horses excitement may predominate. Thisspecies difference reflects in many of the propertiesof the drugs. High doses of morphine willsedate dogs, but not horses or cats. Opioid agonistsgenerally cause miosis, and do so in the dog,but generalized excitement in horses and cats maysometimes be accompanied by mydriasis. Theeffects on the cardiovascular system are very variableand depend on the drug, its dose and thespecies of animal concerned. In general, however,at high doses they cause bradycardia, thought tobe mediated via vagal mechanisms, and this is regularlyseen in dogs. They have minimal directeffect on the heart and their effects on arterialblood pressure may be very variable. Release ofhistamine by morphine and pethidine may causearterial hypotension in dogs. Opioid agonists usuallycause arterial hypertension and tachycardia inhorses – presumably manifestations of the excitementreaction although under some circumstancesbradycardia can occur (Muir et al., 1978; Clarke &Paton, 1988). High doses of opioids produce musclerigidity in all species of animals, includingdogs.It must be emphasized again that the presenceor absence of pain can have a major influence onthe response to opioids, and horses and cats inpain when these drugs are given may show noadverse reactions to doses which would causeexcitement in normal animals.Use and choice of opioid analgesicsOpioid drugs may be used to provide analgesiabefore, during and after surgery as well as in combinationwith sedative drugs for ‘chemical control’.The choice of opioid will depend on thedegree of analgesia needed, the speed of onset ofthe drug’s action and the length of action required,as well as on the side effects that can be tolerated inthe circumstances. When analgesia is needed duringsurgery, an opioid with a fairly long actionmay be used for premedication (e.g. morphine orbuprenorphine), or a short acting drug such asfentanyl or alfentanil given during surgery.Where potent agonists such as fentanyl oralfentanil are used to provide a major componentof anaesthesia for surgery, respiratory depressionmay be severe and respiratory support withintermittent positive pressure ventilation of thelungs and oxygen supplementation will be necessary.A similar degree of respiratory depressionduring the recovery period is unacceptable ifless support is available. As all opioids crossthe placenta, care must be taken if they are usedat parturition, although naloxone may be usedto antagonize respiratory depression in theneonate.Dysphoric or hallucinatory effects will not be aproblem during general anaesthesia and are oftenprevented in conscious animals by the use of sedatives,but may cause distress if drugs causing theseeffects are given to unsedated, ambulatory animals.Because opioids often have a synergisticdepressant action in combination with sedatives oranaesthetics, doses (particularly of the morepotent agents) may need to be reduced when combinationsof these drugs are used. The use of partialagonist drugs was encouraged by theirfreedom from statutory controls in many countries,but now in the USA pentazocine, butorphanoland buprenorphine are all FDA controlledand in the UK buprenorphine and pentazocine arecontrolled drugs while butorphanol is a prescription-onlymedicine.

96 PRINCIPLES AND PROCEDURESEpidural opioidsOpioids, including morphine, oxymorphone, fentanyl,sufentanil and butorphanol have been usedby the epidural route in order to try to achieveanalgesia without central and respiratory depressionduring and after surgery. There are differencesin receptor pharmacology and extrapolationfrom human experience may be unwise. In man,respiratory depression may occur and is sometimesseriously delayed, but this does not seem tobe a clinical problem in dogs. Another commonside effect is pruritis in 67–100% of patients,although only serious in 1–10% (Morgan, 1989).Epidural opioids administered through indwellingcatheters may have a role to play in the provisionof prolonged analgesia but in veterinarypractice maintaining asepsis in the management ofindwelling epidural catheters can present problems.When they are used by epidural injectioncare must be taken to ensure that the solution doesnot contain a preservative, for this may damagenerves.OPIOID AGONISTSMorphineMorphine, the principal alkaloid found in opium(the partially dried latex from the unripe capsuleof Papaver somniferum) is still the ‘gold standard’against which other analgesics are assessed. As thealkaloid itself is insoluble in water, it is supplied asa water soluble salt, usually the sulphate orhydrochloride. Because of its euphoric propertiesin man it is strongly addictive and its use is, therefore,subject to controls.Its major properties are those of producing analgesia,respiratory depression and constipation.Small doses have minimal effects on the cardiovascularsystem but higher doses may cause bradycardiaand hypotension in dogs. In these animalshistamine release may contribute to its hypotensiveaction. In horses, hypertension may occur withminimal changes in heart rate (Muir et al., 1978).Doses of 0.1 to 0.3 mg/kg by intramuscularinjection will usually provide good analgesia inmost species of animal if they are in pain when thedrug is given, but in cats it may be safer to restrictthe dose to 0.1 mg/kg. Excitement reactions,bradycardia and histamine release are more commonwhen the drug is given by the intravenousroute and even after intravenous injection analgesiamay not become apparent for some 15 minutes.PapaveretumThe mixture of drugs now marketed as papaveretumcontains morphine, papaverine andcodeine and is currently available in two strengths.This combination differs from that sold previousto 1993 under the Trade name, ‘Omnopon’ whichalso contained a number of other morphine alkaloids.In veterinary anaesthesia, the advantage of‘Omnopon’ over morphine alone was that itcaused less vomiting in ambulatory dogs.‘Omnopon’ was commonly used with hyoscine inthe preparation ‘Omnopon-Scopolamine’, whichcontained 20 mg of the alkaloids with 0.4 mg ofhyoscine (‘Scopolamine’) per ml. The combinationwas a time-honoured premedication in medicalanaesthesia, and a 1 ml vial of the ‘Omnopon-Scopolamine’ mixture with 3 mg of acepromazinewas useful to sedate and control vicious dogs. Theauthors have no experience with the currentpreparation of papaveretum, but it is probable thatit will be equally effective as a canine sedativewhen combined with hyoscine (still available inthe UK as Scopolamine) and acepromazine.PethidinePethidine (‘meperidine’ in North America) is only1/10 th as potent as morphine and although its primaryactions are typical of agonist opioids it alsoappears to have atropine-like properties. Unlikemorphine, it appears to relax intestinal spasm andso is particularly useful in equine spasmodic colic.It rarely, if ever, causes vomiting in dogs or catsand has little effect on the cough reflex. Dosesgiven by i.m. injection have little effect on arterialblood pressure but pethidine is a potent histamineliberator and because of this its i.v. injection canresult in severe hypotension in dogs.In large animals doses of 1 mg/kg by i.m. injectionand in dogs 1–2 mg/kg produce generally satisfactoryanalgesia. In cats i.m. doses of 10–20 mgper cat may be given. Pethidine appears to have a

SEDATION, ANALGESIA & PREMEDICATION 97short half life in animals (Alexander & Collett,1974; Kalthum & Waterman, 1988) and these dosesonly give effective pain relief for 1.5 to 2 hours.Polyester film backingFentanyl reservoirMethadoneMethadone is a synthetic agonist, approximatelyequipotent to morphine in terms of analgesia,although it produces less sedation in dogs andmore ataxia in horses. It is less likely to causeanaphylactoid reactions than is pethidine. It hasbeen widely used in horses at i.v. or i.m. doses of0.1 mg/kg, higher doses carrying an increased riskof ataxia and excitement. The dose for the dog isgenerally accepted to be 0.25 mg/kg.Methadone has frequently been used in dogsand horses as part of sedative/opioid combinations.A preparation used on the Continent ofEurope, ‘Polamivet’, contains 2.5 mg of thelaevorotatory isomer together with 0.125 mg of anatropine-like compound, diphenylpiperidonoethylacetamidehydrochloride, per ml of solution andthis mixture is widely used in combination withthe phenothiazine derivative, propionyl promazine,‘Combelen’, for sedation of horses anddogs.FentanylThis drug is about 50 times as potent as morphine.It is a pure agonist capable of producing a highlevel of analgesia, sufficient to allow surgery(Tobin et al., 1979). Effective following i.v. injection,it is also rapidly absorbed across mucous membranes.Following i.v. injection it is effective in4–7minutes and, although claimed to be short acting(15 to 20 minutes) this is largely due to redistributionin the body so that cumulative effects occurwith prolonged or high dosages.The pharmacology of fentanyl in animals hasbeen well described (Tobin et al., 1979; Sanford,1984). In dogs, rats and primates it produces sedationand myosis, whilst in mice, cats and horses itcauses excitement with mydriasis. Horses show avery marked locomotor response, pacing increasingwith dosage, yet they show very little ataxia(Tobin et al., 1979). As with all opioid agonists,analgesia is accompanied by respiratory depressionand when the drug is used in dogs duringRelease membraneAdhesiveFIG. 4.1 Diagrammatic section through a fentanyl patch(fentanyl transdermal system;Duragesic,Janssen).general anaesthesia IPPV is usually necessary ifthe dose used exceeds 0.2 mg/kg. Fentanyl has littleeffect on the cardiovascular system but usuallycauses some slowing of the pulse. Occasionallysevere bradycardia occurs, necessitating theadministration of anticholinergics.In veterinary practice, fentanyl was initiallyused as part of neuroleptanalgesic mixtures fordogs (Marsboom & Mortelmans, 1964) but it isnow popular in balanced anaesthesia techniquesand for postoperative analgesia in intensive care.In man, the use of adequate doses of opioids suchas fentanyl has been shown to reduce the stress andcatabolic responses to anaesthesia and surgery, andto reduce morbidity. There is some evidence toindicate that a similar reduction in stress responseoccurs in animal patients given these analgesicsduring surgery.A recent development has been the availabilityof cutaneous patches for the continuous, controlledadministration of fentanyl (Fig. 4.1) and althoughthere is still some debate about the best way toemploy them they are apparently being used ondogs and cats in the USA. In the UK they areavailable for use in man (Janssen-Cilag Ltd.,Saunderton, High Wycombe, Bucks, HP14 4HJ)and designed to release 25 µg/hour, 50 µg/hour, 75µg/hour and 100 µg/hour.They all produce a skin depot of the drug so thatfentanyl continues to be absorbed into the circulationfor some time after removal of the patch. Therewas concern that drug abuse might be encouragedby the use of these patches in canine outpatients,however, recommended disposal of the patch afterits removal from the skin entails no more than foldingit over and discarding into the household trashbin. Their use in animals is not licenced but, inthe future, they may make the provision of

98 PRINCIPLES AND PROCEDURESpostoperative analgesia for day case surgery easierto ensure. Egger et al.(1998) recommended thatbecause of inter-individual and intra-individualvariation in plasma fentanyl concentrationsobtained from the use of 50, 75 and 100 µg/hourpatches, they should be applied 24 hours before theanticipated time that analgesia will be required.AlfentanilThis fentanyl derivative is only one-quarter aspotent an analgesic as fentanyl itself but has theadvantage of being rapidly effective (1 to 2 minutesfollowing i.v. injection). It has been claimed tobe shorter acting although studies of its pharmacokineticsin dogs throw some doubt on this since ithas been shown to be more cumulative followingrepeated doses. Alfentanil plasma levels decaytriphasically in dogs (t 1/2 β = 104 minutes), and lessthan 1% of the drug is excreted unchanged asalfentanil, metabolism into a large number of inactivemetabolites being rapid (Heykants et al., 1982).Analgesia is accompanied by respiratory depressionand very severe bradycardia may occur(Arndt et al., 1986).In dogs alfentanil may be used to reduce theinduction dose of an i.v. anaesthetic although thismay entail production of several minutes ofapnoea. For example, mixing 10 µg/kg of alfentanilwith 0.3 or 0.6 mg of atropine and injectingthis mixture some 30 seconds before injectingpropofol can reduce the dose of propofol neededto induce anaesthesia to less than 2 mg/kg, butapnoea of up to three minutes duration may occur(Chambers, 1989). Similar results follow whenalfentanil at this dose is used prior to the injectionof thiopental. However, with these i.v. anaestheticsapnoea is not nearly so prolonged when the alfentanildose is reduced to 5 µg/kg, while there is stilla desirable reduction in the dose of anaestheticneeded to allow endotracheal intubation. Alfentanilis now often used in intermittent doses to providean ‘analgesic element’ in anaesthetized dogsabout to be subjected to intense surgical stimulationbut in spontaneously breathing animals the individualdoses should not exceed 5 µg/kg if there areno facilities for prolonged IPPV of the lungs.In Munich, Erhardt has used etomidate/alfentanil(Erhardt, 1984; Erhardt et al.; 1985, 1985a) toproduce short periods of anaesthesia followed by arapid recovery in a wide range of species.RemifentanilRemifentanil is a fentanyl derivative with an esterlinkage which is rapidly broken down by non-specifictissue and plasma esterases and is responsiblefor its unique characteristics. It is a pure µ agonist(James et al., 1991) and the EEG effects of remifentanilare similar to those of other opioids in dogs(Hoffman et al., 1993). Clearance is unlikely to bedependent on renal or hepatic function andbecause in vitro it is a poor substrate for butyrylcholinesterases(pseudocholinesterases), its clearanceshould be unaffected by cholinesterasedeficiency induced by anticholinesterase flea collars.Currently, remifentanil is formulated inglycine, an inhibitory neurotransmitter, and consequentlyit should not be given by spinal orextradural injection.Rapid biotransformation to minimally activemetabolites should be associated with a short, predictableduration of action with no accumulation ofeffect on repeated dosing or with continuous infusion.Its effects are antagonized by naloxone and itspotency is similar to that of fentanyl, and 15 to 30times that of alfentanil. Bolus i.v. injection is said tocause a reduction of about 20% in mean arterialblood pressure and heart rate, but more detailedhaemodynamic investigations are awaited. Recoveryfrom remifentanil anaesthesia is said to bemuch more rapid than for any other opioid studiedto date, especially after continuous infusions maintainedfor six or more hours ( Michelsen et al., 1996).To date there are no reports of the clinical useof remifentanil in veterinary practice. It maybe that it will be used widely (perhaps in place ofnitrous oxide during general anaesthesia) becauseof its predictability, short duration of action andeasily reversible effects, but its exact niche in veterinaryanaesthesia remains to be seen.Other fentanyl derivativesSufentanil,lofentanil and carfentanilSufentanil is approximately 10 times as potent asfentanyl, while lofentanil has a very potent and

SEDATION, ANALGESIA & PREMEDICATION 99exceptionally long lasting effect. Neither of thesedrugs has been used extensively in veterinarymedicine. Carfentanil is one of the most potentopioids known. It is said to be 3–8 times as potentas etorphine and has proved to be useful inelephants (Bengis et al., 1985), although at the concentrationsused it is a dangerous drug to handlesince it is rapidly absorbed across mucous membranes.An antagonist drug suitable for use inhumans should be readily available whenever carfentanilis used.EtorphineEtorphine is a very potent derivative of morphinewhich is claimed to be effective in a dose ofabout 0.5 mg per 500 kg. It appears to have allthe properties of morphine but equipotentdoses cause more respiratory depression. Itsvery great potency constitutes its sole advantagein that an effective dose for a very large animalcan be dissolved in a small volume of solvent,enabling it to be used in dart gun projectiles forimmoblizing wild game animals. In anaestheticpractice this very same potency makes it a difficultdrug to handle and constitutes a hazard to theanaesthetist.Etorphine is an extremely long acting compoundand recovery from its effects is also delayedby enterohepatic recycling. Its action is usually terminatedby the use of diprenorphine, a specificantagonist, but relapse into deep sedation mayoccur. The drug has the highly undesirable propertyof producing stimulation of the central nervoussystem before depressing it and this results in aperiod of excitement. In an attempt to overcomethis, etorphine is marketed in fixed ratio combinationswith phenothizine tranquillizers (‘LargeAnimal Immobilon’ with acepromazine and‘Small Animal Immobilon’ with methotrimeprazine).Should accidental self-administrationoccur, death can result if the antidote is not readilyavailable.BuprenorphineBuprenorphine is a partial agonist that is popularas a premedicant and postoperative analgesicin cats, dogs and laboratory animal where it is usedby the i.v., i.m. and s.c. routes. Although in man it isgiven in the form of a sublingual tablet, sublingualabsorption is difficult to achieve in animals andoral administration is ineffective as the drug is brokendown during first pass through the liver.This drug is unusual in that its associationand dissociation with receptors is very slow.Thus, even after i.v. injection it has a prolongedonset of action (30 minutes or longer), a factoften forgotten in its use. Its long durationof action (known to be about eight hours in man) isdue to its slow dissociation from receptorsand analgesia remains long after it can nolonger be detected in the blood by mostassay methods. This tight binding to receptorsmeans that its actions are very difficult to reversewith naloxone, although pretreatment with naloxonewill prevent its effects. Should respiratorydepression result from the use of buprenorphine itshould be treated with IPPV of the lungs, or withnon-specific respiratory stimulants such asdoxapram.The analgesic dose–response curve is bellshaped,higher doses antagonizing analgesiaalready produced by lower doses but higher dosesdo not antagonize the respiratory depression oncethis has reached a plateau. In the authors’ experienceserious respiratory depression is rare with theusual clinical doses but as its onset may be delayed,when it does occur, it is important that any animalgiven the drug remains under close observationfor at least two hours after its administration. Onits own, in clinical doses, it does not appear tocause sedation, or to cause excitement in susceptiblespecies of animal, but its use towards theend of surgery slows recovery from anaesthesia. Itseffects on the cardiovascular system are minimal.Doses used in dogs and cats vary from 6 to10µg/kg and in horses the authors have found itan effective analgesic at doses of 6 µg/kg fororthopaedic cases. However, the bell-shapednature of the dose–response curve must be consideredand if these doses are inadequate for painrelief, they may be followed by doses of a pureagonist drug. Buprenorphine has also been extensivelyused with α 2 adrenoceptor agonists in sedativecombinations.The popularity of the drug in the UK hasundoubtedly been due to its prolonged length of

100 PRINCIPLES AND PROCEDURESaction, that it provides better analgesia than can beobtained with other partial agonists and, untilrecently, its freedom from control under theMisuse of Drugs Act 1971.ButorphanolIn the UK this drug is currently not subject to controlsunder the Misuse of Drugs Act 1971. It is usedin cats, dogs and horses for analgesia and in sedativecombinations with α 2 adrenoceptor agonists.Butorphanol is also used in dogs for its antitussiveeffect. In dogs and horses it is said to have minimaleffects on the cardiovascular system (Trim, 1983;Robertson et al., 1981) but caution may be in orderhere for in man it causes increased pulmonary vascularresistance and, at high doses, hypertension,so it is not recommended for patients with cardiovasculardisease.In experimental horses it has been used in dosesof 0.1 to 0.4mg/kg but the higher doses caused restlessnessand apparent dysphoria (Kalpravidh et al.,1984) and the dose currently used clinically is 0.02 to0.1mg/kg by i.v. injection, which seems to be particularlyeffective for the relief of mild colic. However,in the authors’ experience even this dose mayinduce walking behaviour in unrestrained animals.Doses of 0.1 to 0.5 mg/kg by i.m. or s.c. injectionhave been found to give effective analgesia for upto four hours in both dogs and cats (Paddleford,1988). In experimental studies visceral analgesiawas found to be superior to somatic analgesia,and lower doses superior to higher doses, possiblyindicating that, like buprenorphine, thedose–response curve is bell shaped. Butorphanolmay be given orally for analgesia although doses5–10 times those by injection are required to producean equivalent effect.PentazocineIn man this partial agonist has lost its earlier popularitydue to producing a high incidence of dysphoriaand hallucinatory responses, coupled withcausing a marked increase in pulmonary vascularresistance. Moreover, because of its abuse potential,in the UK it is controlled under the Misuse ofDrugs Act 1971. Although it is impossible to assessdysphoria in animals most veterinarians withextensive experience of pentazocine have seensigns they associate with such an effect, particularlyfollowing high doses.Despite these problems pentazocine has beenquite widely used in veterinary practice, dosesof 1 to 3 mg/kg being said give to three hours ofpain relief (Taylor & Houlton, 1984; Sawyer &Rech, 1987; Paddleford, 1988). Pentazocine canbe given orally but first pass liver metabolismmeans that high doses are necessary. In the experimentalhorse colic model doses of 0.5 to 4.0 mg/kghave been tested, the higher doses giving riseto ataxia and muscle tremors. The recommendeddose for the relief of colic pains in horses is0.33mg/kg i.v., followed 15 minutes later by a similari.m. dose.NalbuphineAlthough this drug has minimal cardiovasculareffects and appears to cause few dysphoric reactions,it has a low ceiling of analgesia and is notrecommended for relief of severe pain. In experimentaldogs it has been found that doses of0.75 mg/kg give reasonable visceral analgesia;somatic analgesia is poor and analgesia is alwaysinferior to that provided by butorphanol. As part ofa sedative combination for use in horses, in thedoses employed for this, nalbuphine alone producesno discernible unwanted effects in pain-freehorses.SEQUENTIAL ANALGESIASequential analgesia is a term introduced to describethe use of partial agonists subsequent to pureagonists (usually fentanyl) in an attempt to reverseresidual respiratory depression whilst maintaininganalgesia. First attempted with pentazocine,buprenorphine, butorphanol and nalbuphine havealso been used for this purpose (Mitchell & Smith,1989). On theoretical grounds buprenorphineshould be the least efficient and nalbuphine themost because of their µ agonist and antagonistproperties (Table 4.2), and nalbuphine has beenwidely recommended for use in man for this purpose.In laboratory practice, buprenorphine hasbeen used to reverse the effects of high dose fentanyl(Flecknell, et al., 1989).

SEDATION, ANALGESIA & PREMEDICATION 101The idea of agonist/antagonist analgesia is notnew for many years ago a combination of pethidinetogether with its antagonist levallorphan wasmarketed, but was found to produce no less respiratorydepression than pethidine alone atequianalgesic doses. It is clear that the final outcomeof sequential analgesia must be the result of adelicate balance of activities at the various receptorsand the ‘reversing’ drugs must be given withgreat care according to the need of the individualpatient.their use as analgesics, are used for their antagonisticproperties. Nalorphine was the first to be usedas an opioid antagonist but has now been supersededby naloxone. Diprenorphine is marketed asa specific antagonist of etorphine and in animals itappears to be very efficient in this role. However asit causes hallucinations in man it is only licensedfor use in animals and in medical practice naloxoneremains the drug of choice for countering theeffects of etorphine.OPIOID ANTAGONISTSPure antagonistsNaloxoneNaloxone is a pure antagonist at all opioid receptorsand so will reverse the effect of all opioid agonistsbut it is less effective against partial agonists. Inman, reversal of opioid actions with naloxone issometimes accompanied by tachycardia but thereare no reports of this in the veterinary literature.The drug is fairly short acting and its effects maywear off before those of the previously administeredagonist so that repeated doses may beneeded. This is particularly important in veterinarymedicine where large and frequent doses ofnaloxone are necessary to counter the accidentalself-administration of the potent long acting agent,etorphine.Naloxone given to an animal that has notreceived an opioid may temporarily alter itsbehaviour and it has been claimed that it is effectivein stopping horses crib-biting (Booth, 1988).Naloxone is thought by some to have a role in thetreatment of shock (Booth, 1988).NaltrexoneNaltrexone is a long acting derivative of naloxoneand although not apparently often used in veterinarypractice it could prove useful should a longacting pure antagonist be required.Partial agonists used as antagonistsSome partial agonists, which either give poor analgesiaor produce dysphoria sufficient to precludeSEDATIVE–OPIOID COMBINATIONSWhen opioids are combined with sedative drugs,synergism seems to occur, sedation and analgesiabeing greater than that capable of being achievedby either drug alone. The use of the sedative willoften also prevent any excitement effects thatmight occur with the opioid alone. There is nothingnew about the use of such combinations, veterinarianshaving used them for many years tomake animals more manageable (Amadon &Craige, 1936). The range of sedative/opioid mixturesin use for sedation and control of animals isnow enormous, α 2 adrenoceptor agonists, neurolepticagents and benzodiazepines all having beencombined with a wide variety of agonist and partialagonist opioids. Depth of sedation achieveddepends primarily on the opioid employed, partialagonists or less potent agonist combinationsproducing sedation whereas large doses of potentopioids such as fentanyl or alfentanil can achieveanaesthesia. Unfortunately, severe respiratorydepression may accompany the use of these highdose opioid techniques. Suitable combinations forsedation, control and anaesthesia in each speciesof animal are given in later chapters of this book.The term neuroleptanalgesia has been used todescribe the combination of opioids with phenothiazinesor butyrophenones (neuroleptics). Theprinciples of their use are the same as outlinedabove for any sedative/opioid combination butthe neuroleptic agents have the specific propertyof reducing opioid-induced vomiting in dogs.Neuroleptic techniques can be used in two ways.At comparatively low opioid dose rates they canbe used for control, or as premedication beforegeneral anaesthesia; at higher dose rates they can

102 PRINCIPLES AND PROCEDURESTABLE 4.4 Composition of some commerciallyavailable neuroleptanalgesic mixturesCommercial AnalgesicnameNeurolepticThalamonal Fentanyl 0.05 mg/ml Droperidol 20 mg/mlHypnorm Fentanyl 0.315 mg/kg Fluanisone 10 mg/mlImmobilon SA Etorphine 0.074 mg/ml Methotrimeprazine18 mg/mlImmobilon LA Etorphine 2.45 mg/ml Acepromazine10 mg/mlbe used to produce sufficient depression of thecentral nervous system to enable surgery to be performed.This latter use is sometimes termed ‘neuroleptanaesthesia’and was the way in which thetechnique was first used in veterinary medicine(Marsboom & Mortelmans, 1964), but it is associatedwith profound respiratory depression andshould not be used unless facilities for respiratorysupport are available.To obtain the best results the neuroleptic shouldbe administered first and, when it is fully effective,the analgesic should be given to produce thedesired result. In veterinary medicine, however,for convenience it is usual to employ commerciallyavailable fixed ratios of the two drugs and it mustbe accepted that this ratio may not be optimal forany particular animal.The composition of commercially availablemixtures of fentanyl/butyrophenone tranquillizerare given in Table 4.4. All have similar propertiesand may be considered together. They are used indogs, primates and rodents, but they are contraindicatedin cats because fentanyl may causeviolent excitement in these animals. They are usuallyused to produce deep sedation with profoundanalgesia sufficient for procedures such asendoscopy, or the lancing of a superficial abscess,but are inadequate for major surgery. The rationalefor using the short acting fentanyl with long actingbutyrophenones is not obvious, but the combinationappears effective.Fentanyl has been used with fluanisone for neuroleptanalgesiain a 1:50 mixture (FluanisoneComp.). Given at a dosage level of 0.1 mg/kg offentanyl with 5 mg/kg of fluanisone by slow i.v.injection it produced a short period of anaesthesiaafter short and mild excitement. Recovery wasslow, the time varying from 2 to 10 hours beforerecovery to full consciousness. Respiratory effectsare variable, with both hyperpnoea and respiratorydepression occurring. The advantages of themixture include ease of administration, wide safetymargin, quiet postoperative state, reversibilitywith narcotic antagonists (such as naloxone),and tolerance by animals in poor physical condition.Disadvantages include variable responsein certain breeds, the spontaneous movementswhich occur, the need to employ nitrous oxide orlocal analgesia when major surgery is to beperformed, and the possibility of respiratorydepression.Fentanyl has also been used in the UK in combinationwith fluanisone, as the preparation‘Hypnorm’. Diarrhoea has been reported to followthe administration of this mixture in over 24% ofcanine patients.The effects of fentanyl with fluanisone and fentanylwith droperidol in pigs have been studiedbut neither mixture produced better sedation thandroperidol alone.The results obtained by neuroleptanalgesictechniques are more impressive in monkeys. Inthese animals the technique may offer distinctadvantages over the more conventional methodsof anaesthesia especially when skilled assistance isnot available.‘IMMOBILON’‘Immobilon’ is marketed for both small and largeanimal use, the concentrations of etorphine andthe tranquillizer in each preparation being asshown in Table 4.4. At the doses recommended bythe manufacturers the preparations cause intensecentral nervous depression with considerableanalgesia, allowing major surgery to be carriedout. When surgery is completed it was recommendedthat the effects of the etorphine (but not ofthe phenothiazine tranquillizer) be reversed by theuse of the specific antagonist (‘Revivon’). LARevivon contains 3.0 mg/ml and SM Revivon0.272 mg/ml of diprenorphine.The effects of ‘Immobilon’ in horses are whatmight be expected to follow such high doses of anopiate drug in this species of animal. Intramuscularinjection regularly leads to excitement dur-

SEDATION, ANALGESIA & PREMEDICATION 103ing induction; after i.v. injection the horse becomesrecumbent within one minute and although excitementmay occur it is much less marked. Oncerecumbent, intense muscular activity makes theanimal very stiff and violent continuous tremorsoccur. The muscles relax somewhat after about20 minutes. Blood pressure and heart rate increaseto very high levels but respiration is severelydepressed. Following the i.v. injection of ‘Revivon’most horses regain the standing position within afew minutes. Occasionally, horses become excitedshortly after standing and a further excitementphase may occur several hours later due to enterohepaticrecycling of the etorphine. The disadvantagesassociated with the use of ‘Immobilon’ indomestic animals far outweigh the advantages.‘Immobilon’ and other etorphine-containingmixtures have been extensively used for the captureof wild game. Although generally used as‘knockdown’ doses, as in horses, they are alsocommonly used at lower dose rates whereby theanimals (elephants and giraffes) became sedatedbut remain standing. ‘Immobilon’ is not recommendedfor wild felidae (nor domestic cats!).In man etorphine is extremely potent and theuse of ‘Immobilon’ constitutes a danger to theanaesthetist and assistants. Should an accidentoccur, naloxone is recommended as the drug ofchoice for treatment of human beings, but severaldoses may be needed to maintain respiration untilmedical help can be obtained.ANTICHOLINERGIC AGENTSAnticholinergic agents are widely used in anaesthesiato antagonize the muscarinic effects ofacetylcholine and thus to block transmission atparasympathetic postganglionic nerve endings.The main purposes are:1. To reduce salivation and bronchial secretions2. To block the effects of impulses in the vagusnerves3. To block certain of the effects produced bydrugs which stimulate the parasympatheticsystem.The reduction of salivation and bronchial secretionis necessary if irritant volatile anaesthetics such asether are used, but it is not essential with modernhalogenated anaesthetics like halothane andisoflurane. However, in small dogs and in cats,even a little secretion may be enough to give rise tosignificant respiratory obstruction and in suchsmall patients it is arguably advisable to administeranticholinergics before any anaesthetic.Ruminants produce large quantities of saliva butanticholinergic drugs merely make their salivamore viscid and thick and more likely to create respiratoryobstruction, so these drugs should not beused.Some drugs, in particular the α 2 adrenoceptoragonists and, in high doses, the opioids, can causemarked vagus-mediated bradycardia. Also, underlight anaesthesia, surgery of the head and neck isprone to trigger vagal reflexes, and the horse, dogand cat seem to be most at risk from these disturbances.In cats the oculocardiac reflex is well knownto result in bradycardia and even cardiac arrest;stimulation of the nose or other similarly sensitivestructures can have the same effect or cause laryngospasm.In horses, stimulation about the headand neck can produce sudden cardiac arrest withouta prior warning of bradycardia.Anticholinesterase drugs such as neostigmineare used to antagonize the block produced by competitiveneuromuscular blocking drugs and theiruse must be preceded or combined with one of theanticholinergic drugs to block the muscariniceffects of the released acetylcholine. Also, thedepolarizing agent suxamethonium has effectssimilar to those of acetylcholine and, at least indogs and cats, an anticholinergic ‘cover’ should beemployed when this relaxant is used.In recent years the advisability of routine premedicationwith anticholinergic drugs has beenquestioned. These drugs certainly have side effectsand the tachycardia they induce may be undesirablewhen it reduces stroke volume or cardiac output.Disturbance of vision may cause a cat or horseto panic. Reduced gut motility may cause colic inhorses. In man, considerable discomfort resultsfrom dry mouth in the postoperative period and,presumably, this may also be the case in animals.These disadvantages must be weighed against theadvantages already mentioned.Current practice, where ether is not to be used,seems to be not to use anticholinergic drugs for

104 PRINCIPLES AND PROCEDURESroutine premedication, but to reserve them for correctivemeasures should bradycardia occur duringthe course of the anaesthetic. This, of course,assumes that monitoring is adequate to detect thebradycardia. However, it must be rememberedthat following i.v. injection atropine may causefurther bradycardia through a central effect beforeblocking at the vagal endings and increasing theheart rate. Thus, it can be argued that in dogs, catsand pigs the i.m. use of atropine before inductionof anaesthesia is preferable to waiting for bradycardiaand heart block to appear during the courseof anaesthesia and correction by i.v. administration.The use of i.v. atropine or glycopyrrolate tocorrect some drug-induced bradycardias has beenshown to be associated with further bradycardiaand heart block (Richards et al., 1989). Thus, thedecision to include an anticholinergic agent in premedicationmay be based on the species of animalconcerned, its size, the drugs to be used for andduring anaesthesia, the likelihood of complicationsfrom bradycardia or vagal reflexes, the levelof monitoring in use and any specific contraindications.The main contraindications are in conditionsassociated with tachycardia and in certain forms ofglaucoma which are aggravated by dilatation ofthe pupil.AtropineAtropine, the most important of the alkaloidsobtained from Atropa belladonna (deadly nightshade),is used in anaesthesia as its water-solublesulphate. Its metabolism is not the same in all speciesof animal. When administered to dogs, atropinedisappears very rapidly from the bloodstream.Part of the dose is excreted unchanged in the urine,part appears in the urine as tropine and theremainder is apparently broken down in the bodyto as yet unidentified substances. In cats, atropineis hydrolyzed by either of two esterases which arefound in large quantities in the liver and kidneys.These esterases are also found in rabbits and rats.Atropine inhibits transmission of postganglioniccholinergic nerve impulses to effector cellsbut inhibition is not equally effective all over thebody and atropine has less effect upon the urinarybladder and intestines than upon the heart andsalivary glands.The drug has unpredictable effects on thecentral nervous system. Certain cerebral andmedullary functions are initially stimulated thenlater depressed, so that the final outcome dependson the dose used and the route of administration.Clinical doses may produce an initial slowing ofthe heart due to stimulation of vagal centres in thebrain before its peripheral anticholinergic effectsoccur. Atropine overdose causes a ‘central cholinergiceffect’ with fluctuations between hyperexcitabilityand depression. Although atropine is, ingeneral, a very safe drug with a wide therapeuticmargin, occasional cases have been reportedwhere an individual person or animal hasappeared unduly sensitive to the central effects.The main action of the drug is on the heart rate,which usually increases due to peripheral inhibitionof the cardiac vagus: the initial slowing due tocentral action is only seen before the onset ofperipheral inhibition. Arterial blood pressure isusually unchanged, but if already depressed byvagal activity due to reflex or drug action (e.g.halothane) it will be raised by the administrationof atropine. In man, an increase in the incidence ofcardiac arrythmias has been observed duringanaesthesia following atropine premedication, butK. W. Clarke (unpublished observations) foundthat atropine reduced the incidence of ventricularextrasystoles in cats anaesthetized with a varietyof halogenated volatile anaesthetics. Cardiacarrhythmias (e.g. bigeminy) in dogs previouslyattributed to atropine were probably due to barbituratesand are often seen in the absence ofatropine.The minute volume of respiration is slightlyincreased due to central stimulation. Bronchialmusculature is relaxed and bronchial secretionsare reduced. Both anatomical and physiologicaldead space are increased by atropine (Nunn& Bergman, 1964). Studies in dogs at the CambridgeVeterinary School and elsewhere have notshown any hypoxaemia attributable to atropineadministration.Atropine has marked ocular effects. Mydriasisresults from the local or systemic administration ofatropine. Except in dogs, where the parenteraladministration of clinical doses of atropine doesnot alter pupillary size, the mydriasis may interferewith the so-called ‘ocular signs’ of anaesthe-

SEDATION, ANALGESIA & PREMEDICATION 105sia. The ocular effects also result in visual disturbancesand animals so effected must beapproached with great caution as they may haveproblems in judging distances. This is particularlyimportant in horses and cats as both these animalstend to panic in response to sudden movementswhich they do not see clearly.Although atropine reduces muscle tone in thegastrointestinal tract, at the doses used for premedicationthis effect is minimal. The passage ofbarium meals along the gut of the dog is not appreciablyslowed by atropine premedication but it ispossible that the incidence of postanaesthetic colicin horses is increased by the use of this drug.Because of the different ways in which theymetabolize the drug, the effectiveness of a givendose varies according to the species of animal butits therapeutic index is such that a wide range ofdoses can be recommended. In dogs, doses from0.02 to 0.05 mg/kg are employed, while in catsdoses of up to 0.3 mg (approximately 0.1 mg/kgfor an adult cat for example) are perfectly safe.Pigs may be given 0.3 to 1.8 mg according to size.The exact dose is largely determined by the factthat, at least in the UK, atropine sulphate for injectionis still supplied in a solution of 0.6 mg/ml – alegacy of earlier days when doses were measuredin grains. A large animal preparation containing10mg/ml is now available, and this enables horsesto be given doses between 10 and 60 mg muchmore conveniently than was previously possible.To neutralize the muscarinic effects of anticholinesterasessuch as neostigmine, in cats, dogsand pigs 0.6 to 1.2 mg of atropine are given slowlyi.v. 2 to 5 minutes before these agents are injected,or else mixed in the syringe and injected with theanticholinesterase. In horses doses of 10 mg appearto be adequate for this purpose.GlycopyrrolateGlycopyrrolate is a quaternary ammonium anticholinergicagent with powerful and prolongedanti-sialagogue activity. As an anti-sialagogue it isabout five times as potent as atropine. In man, clinicaldoses have an almost selective effect on salivaryand sweat gland secretion. Cardiovascularstability is excellent, there being little change inheart rate, and there is a reduction in cardiacarrhythmias compared with their incidence afteratropine. This cardiovascular stability wasthought to make it particularly useful for combinationwith anticholinesterases for antagonizing theeffects of non-depolarizing neuromuscular blockingagents and, indeed, as glycopyrrolate isclaimed to have a more rapid onset of action thanatropine, a preparation of neostigmine with glycopyrrolateis available for this purpose. However,work on anaesthetized human patients showed nodifference in the cardiovascular effects of atropineand glycopyrrolate other than in the time of onsetof action – glycopyrrolate taking 2 to 3 minutes tobecome effective following i.v. injection (Short &Miller, 1978).Glycopyrrolate has now been used widely inveterinary practice in doses of 0.01 to 0.02 mg/kg(Short et al., 1974). However, although it has beensatisfactory in preventing excessive salivation andbradycardia, it has proved disappointingly similarto atropine in its effects on the heart rate (Richardset al., 1989). A comparison of atropine given i.v. atdoses of 0.02 to 0.04 mg/kg with i.v. glycopyrrolate(0.02 and 0.01 mg/kg) in dogs with drug-inducedbradycardia showed that both agents caused ahigh incidence of cardiac arrhythmia, includingatrioventricular block, during the first three minutesafter injection. This is surprising since glycopyrrolatedoes not readily cross the blood–brainbarrier and suggests that arrhythmias may be dueto mechanisms other than central stimulation.The fact that the drug does not readily cross theblood–brain barrier means that it has little centralaction, producing less effect on vision than otheranticholinergic agents and thus it could be theanticholinergic of choice in horses and cats.HyoscineHyoscine is an alkaloid resembling atropine,found in the same group of plants but usuallyobtained from the shrub henbane (Hyoscyamusniger). The peripheral actions of hyoscine resemblethose of atropine. However, its relative potency atdifferent sites differs from atropine. It is a morepotent anti-sialagogue but less effective as avagolytic so that its effect on heart rate is less thanthat of atropine when they are given in equipotentdoses for their drying effects. The central effects of

106 PRINCIPLES AND PROCEDUREShyoscine are greater than those of atropine and inhorses it may produce considerable excitement. Ingeneral, although hyoscine is used in man (in spiteof its propensity to cause hallucination) as adepressant of nervous activity, it is not suitable forthis purpose in animals. It has been used as the hydrobromidefor premedication in dogs in doses of0.2 to 0.4 mg and it is often used with paraveretum.PREMEDICATIONPreanaesthetic medication or ‘premedication’helps both the anaesthetist and the animal, for itmakes induction and maintenance of anaesthesiaeasier for the anaesthetist while at the same timerendering the experience safer and more comfortablefor the patient. It implies the administration,usually before, but sometimes at or immediatelyafter, the induction of anaesthesia, of sedatives,anxiolytics and analgesics, with or without anticholinergics.The classic aims of premedication are :1. To relieve anxiety thus apprehension, fearand resistance to anaesthesia.2. To counteract unwanted side effects ofagents used in anaesthesia. Effects which mayrequire modification depend on the species ofanimal and on the drugs used; they includevomiting (mainly in dogs and cats), poor quality ofrecovery, bradycardia, salivation and excessivemuscle tone.3. To reduce the dose of anaesthetic. In many,but not all cases, drug combinations may have alower incidence of side effects than a high dose ofthe anaesthetic would have on its own.4. To provide extra analgesia.The use of anticholinergic agents for premedicationhas been discussed in the previous section.Analgesic agents are essential if the patient is inpain in the preoperative period, but even whenpain is absent, analgesics may increase preoperativesedation, reduce the dose of anaesthetic needed,contribute to analgesia during surgery andeven, if sufficiently long acting, contribute to analgesiapostoperatively. The use of long acting analgesicssuch as buprenorphine is particularlypopular for the contribution they make to allstages of the anaesthetic process. Very potent butshort acting opioids such as fentanyl and alfentanilwill reduce the dose of anaesthetic required, buttheir short action means that further analgesiamust be provided during recovery.The sedative and anxiolytic drugs play themajor role in premedication, improving thequality of anaesthesia and recovery, contributingto anaesthesia and, in some cases counteractingunwanted side effects such as the muscle rigidityproduced by ketamine. By calming the animal inthe preoperative period, the necessary clippingand cleaning is made more pleasant for both theanimal and nursing staff. Moreover, by controllingemotional disturbance the release of catecholaminesis reduced, thus decreasing the chance ofadrenaline-induced cardiac arrhythmias, smoothingthe course of anaesthesia and (usually) ensuringa quiet recovery.The degree of activity of the central nervoussystem at the time when anaesthesia is induceddetermines the amount of anaesthetic which has tobe administered to produce surgical anaesthesia.This activity is lowered by wasting disease, senilityand surgical shock and increased by pain, fear,fever and conditions such as thyrotoxicosis.Sedatives and analgesics decrease the irritability ofthe central nervous system and thereby enhancethe effects of the anaesthetic agents. In general, thedepressant effects of the drugs used in premedicationsummate with those of the anaesthetic andunless this is clearly understood overdosage mayoccur. Most sedative drugs depress respiration,and if given in large doses before anaestheticswhich also produce respiratory depression (e.g.thiopental sodium or halothane), respiratoryfailure may occur before surgical anaesthesia isattained. Premedication must, therefore, beregarded as an integral part of the whole anaesthetictechnique and never as an isolated event.The type of sedative drug chosen for premedicationwill depend on a variety of factors.Phenothiazine derivatives such as acepromazineare good anxiolytics and reduce the incidence ofvomiting. Their use usually results in a calm, butdelayed, recovery and delayed recovery is usuallyto be avoided in horses and ruminants for in theseanimals prolonged recumbency gives rise to problems.To prevent recovery being unacceptably

SEDATION, ANALGESIA & PREMEDICATION 107delayed, doses of the phenothiazine derivativesused for premedication should be below thoserecommended for simply sedating animalswhen anaesthesia is not contemplated. Phenothiazinedrugs undoubtedly increase the chance ofregurgitation at induction of general anaesthesiain ruminants.The α 2 adrenoceptor agonists have a majoreffect in reducing the dose of subsequent anaestheticrequired; doses at the lower end of thedosage range provide profound sedation and areuseful in the animal which is particularly difficultto handle. They also provide some degree of musclerelaxation and are especially effective in counteractingthe muscle tension associated with theuse of drugs such as ketamine.Benzodiazepines provide little obvious preoperativesedation but their muscle relaxing propertiesare useful when drugs such as ketamine are tobe used and they reduce the dose of subsequentanaesthetic needed.Often, more than one sedative drug is used inpremedication. For example, α 2 adrenoceptoragonists and benzodiazepines may be combinedprior to the use of ketamine. However, suchpolypharmacy must be used with care, as manysuch combinations have synergistic activity and itis easy to administer an overdose of anaestheticagents given subsequently.For premedication, drugs can be given by anyone or more of the usual routes of drug administration.The choice is governed both by the natureof the drug to be used and the time which is availablebefore anaesthesia is to be induced. If there isplenty of time the drugs may be given sublingually,by mouth or into the rectum. The rectalroute is not very satisfactory and is only used whenfor some reason the others are impracticable, butthe sublingual route is surprisingly effective for theα 2 adrenoceptor agonists, making it possible tosubdue vicious animals by using a syringe to squirtthe drug into the animal’s open mouth. If only 5 to10 minutes will elapse before anaesthesia is to beinduced, then the i.v. route must be employed. It isalways as well to ensure that the preliminary medicationexerts its full effects before the administrationof a general anaesthetic is begun, otherwiserespiratory depression and even respiratory failuremay occur even during light anaesthesia.In the past it was fairly simple to define the limitsof premedication and when anaesthesia began.Today, with the wide range of different types ofdrugs available, such distinctions are no longerclear. Neuroleptanalgesic techniques may enablesurgery to be carried out without further resort togeneral anaesthetic agents. Dissociative agentssuch as ketamine may be regarded as being drugsfor premedication or for the induction of generalanaesthesia. Hypnotics (e.g. chloral hydrate orpentobarbital sodium) may be used at low dosesfor sedation, or at higher doses to produce hypnosisor even anaesthesia. In clinical practice, exactdefinitions of terminology are unimportant aslong as the anaesthetist clearly understandsthe role played by each drug used, be it ‘premedicant’,‘dissociative agent’ or ‘anaesthetic’, inthe total process in bringing the animal to a statesuitable for the performance of surgery, examination,or whatever else is required. Anxiolytics,sedatives, hypnotics and analgesics all havetheir place in this process. In any particularcase, the choice of drugs, their dose and route ofadministration, gives the anaesthetist the opportunityto demonstrate artistry as well as scientificknowledge.REFERENCESAitken, M.M. and Sanford, J. (1972) Comparativeassessment of tranquillizers in the horse. Proceedings ofthe Association of Veterinary Anaesthetists of Great Britainand Ireland 3: 20–28.Alexander, F. and Collet, R.A. (1974) Pethidine in thehorse. Research in Veterinary Science 17: 136–137.Amadon, R.S. and Craige, A.H. (1936) Observations onthe use of bulbocapnine as a soporific in horses.Journal of the American Veterinary Medical Association41: 737–754.Arbieter, K., Szekely, H. and Lorin, D. (1972)Veterinary.Medical Reviews. (Leverkusen) 3:248.Arndt, J.O., Bednarski, B. and Parasher, C. (1986)Alfentanil’s analgesic, respiratory and cardiovascularactions in relation to dose and plasma concentrationin unanesthetized dogs. Anesthesiology 64 (3):345.Averill, D.R. (1970) Treatment of status epilepticus indogs with diazepam sodium. Journal of the AmericanVeterinary Medical Association 56: 432–434.Bengis, R.G., de Vos, V. and van Niekerk, J. (1985)Immobilisation of the African Elephant. Proceedings ofthe 2nd International Congress of Veterinary Anaesthesia:142–143.

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SEDATION, ANALGESIA & PREMEDICATION 111Muir, W.W., Werner, L.L. and Hamlin, R.L. (1975) Effectsof xylazine and acetylpromazine upon inducedventricular fibrillation in dogs anesthetized withthiamylal and halothane. American Journal ofVeterinary Research 36: 1299–1303.Nichols, A.J., Motley, E.D. and Ruffolo, R.R. (1988)Differential effects of pertussis toxin on the pre- andpostjunctional alpha-2-adrenoceptors in thecardiovascular system of the pithed rat. EuropeanJournal of Pharmacology 145: 345–349.Nolan, A.M. and Waterman, A.E. (1985) Preliminaryresults of a study on the effects of xylazine on airwaypressure in the sheep’s lung. Journal of the Associationof Veterinary Anaesthetists 13: 122–123.Nolan, A.M., Waterman, A.E. and Livingston, A. (1986)The analgesic activity of alpha-2 adrenoceptoragonists in sheep: A comparison with opioids.Journal of the Association of Veterinary Anaesthetists14: 14–15.Nunn, J.F. and Bergman, N.A. (1964) The effect ofatropine on pulmonary gas exchange. 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General pharmacology of the5injectable agents used inanaesthesiaINTRODUCTIONIn the past, injectable or intravenous agents wereregarded as being particularly useful for either theinduction of anaesthesia to be continued by aninhalation technique or for anaesthesia of shortduration. They are now increasingly used as alternativesto inhalation anaesthetic agents when prolongedperiods of anaesthesia are desired. Forthese longer periods they may be given by intermittentinjection or by continuous infusion.While it is perfectly possible to obtain satisfactoryanaesthesia using manual control of infusionrates, the procedure is facilitated greatly bythe use of a computer controlled continuous infusionwhere the anaesthetist specifies the ‘target’blood concentration rather than an infusion rateand the computer is programed to determine theappropriate rate of injection to achieve this targetconcentration. Computer controlled infusions arenot yet so widely used in veterinary anaesthesia asthey are in medical practice, largely because thenecessary pharmacokinetic data are not available,but their use is likely to increase as the necessaryinformation is revealed by research.With intravenous agents (in particular thebarbiturates), the clinical level of anaesthesia ismore related to the intensity of stimulation than itis with most of the inhalation agents. An undisturbedanimal may be breathing quietly and havemarked relaxation of the jaw and abdominal muscles,giving a picture of deep unconsciousness.However, on surgical stimulation the breathingmay accelerate or deepen, muscle relaxation maybe lost, reflex movement of a limb occur, and bloodpressure and heart rate suddenly increase. Hereinlies one of the major hazards of intravenous anaesthesiabecause if this animal is now given sufficientof the intravenous agent to abolish these reactionsto stimulation, a dangerous degree of respiratorydepression may occur when the stimulationceases. Moreover, because of the larger quantityof agent being administered more prolongedunconsciousness can be expected. Althoughsimilar considerations apply to anaesthesia withsome inhalation agents it must always be borne inmind that a major difference between the intravenousanaesthetics and those given by inhalationis that the action of intravenous agents is not asquickly reversible because, unlike the inhalationagents, they cannot be recovered from the patient.Another significant difference from the inhalationagents is that specific receptor sites for manyof the intravenous agents have been identified inthe central nervous system, whereas no such specificreceptors have been shown to exist for theinhalation agents. The inhalation agents act on cellmembranes generally and are much more prone todemonstrate undesirable side effects from theiractions on cell function in the body outside thecentral nervous system.Intravenous anaesthetic agents should,when given in adequate doses, produce loss of113

114 PRINCIPLES AND PROCEDURESconsciousness in one injection site–brain circulationtime so that the dose can be titrated againstthe animal’s requirements. Drugs with a sloweronset of action, such as ketamine, are more difficultto use as induction agents. Rapidity of effectrequires the drug to be lipophilic at physiologicalpH and they must also be non-toxic to any bodyorgan or tissue as well as being non-allergenic.Other important characteristics include biotransformationto inactive metabolites and, even at highdose rates, non-saturability of the enzyme systemsresponsible for their elimination from the bodyThe terms ‘ultra-short acting’ and ‘short acting’were originally used in the classification of theeffects of barbiturates but they have come to beemployed for a wider range of anaesthetic agents.They are both confusing and misleading andshould be reserved for drugs which are indeedbroken down rapidly in the body (propofol, forexample). In contrast to these, return of consciousnessfollowing an intravenous barbiturate such asthiopental (which was originally classified as an‘ultra-short acting’ compound) occurs with a largeamount of active drug still in the body so that if leftundisturbed animals tend to lapse back into a deepsleep from which they can only be aroused withdifficulty.Total intravenous anaesthesia (TIVA) avoids theuse of both volatile agents and nitrous oxide duringanaesthesia. An intravenous analgesic (e.g.fentanyl) ensures adequate pain relief during theperioperative and early postoperative period. Inpractice many prefer to use a combination ofnitrous oxide with intravenous supplementation(intravenous anaesthesia; IVA). In a number ofclinical situations IVA and TIVA can offer advantagesover the more traditional volatile agentanaesthesia.THE BARBITURATESIt is more correct to regard barbituric acid as apyrimidine derivative but it is usually depicted ineither the keto or enol form (Fig.5.1).From Dundeeand Wyant (1988) it seems that the many occurringvariations are all derived by substitutions in the1,2 and 5,5’ positions and that four distinct groupsof compounds can be recognized:(5)H(5') HHHOHC N6 1C 5 2C O Keto form4 3C NOOHC N6 1C 5 24 3C OH Enol formC NOFIG.5.1 Keto and enol forms of barbituric acid.H1. Barbiturates (or oxybarbiturates): 1 = H, 2 = O.2. Methylated oxybarbiturates: 1 = CH 3 , 2 = O.3. Thiobarbiturates: 1 = H, 2 = S4. Methylated thiobarbiturates: 1 = CH 3 , 2 = S.Unconsciousness cannot be produced in one injectionsite–brain circulation time by the intravenousinjection of any of the group 1 compounds; theyhave a very limited use in veterinary practice ashypnotics or sedatives. Group 2 compounds frequently,but not invariably, will produce unconsciousnessin one injection site–brain circulationtime. The methyl group confers convulsive activity,of which tremor, involuntary muscle movementand hypertonicity are manifestations. Intravenousinjection of an adequate dose of one of the Group 3thiobarbiturates produces unconsciousness in oneinjection site–brain time and return to consciousnessis more rapid than after the same dose of thecomparable oxybarbiturate. Methylated barbituratesof Group 4 produce such severe convulsivemanifestations as to preclude their use in clinicalanaesthesia.All barbiturates commonly used as anaestheticsare prepared for clinical use as sodium salts andare usually available as powders to be dissolved inwater or saline before use. Commercial preparationsof most barbiturate anaesthetics contain amixture of six parts of anhydrous sodium carbonateand 100 parts (w/w) of the barbiturate to preventprecipitation of the insoluble free acid byatmospheric CO 2 . Aqueous solutions are stronglyalkaline and are incompatible with acids such as

INJECTABLE ANAESTHETIC AGENTS 115most solutions of analgesics, phenothiazine derivatives,adrenaline and some preparations of neuromuscularblocking drugs. Methohexital is acolourless compound and its solution is readilydistinguishable from the yellow solution of sulphur-containingcompounds.The terminology applied to the barbituratesformerly varied between North America andthe UK, the former using the suffix ‘-al’ and thelatter ‘-one’, hence ‘thiopental’ and ‘thiopentone’referred to the same compound. The use of the ‘-al’suffix is now universal.THIOPENTAL SODIUMIn the UK thiopental (thiopentone) was introducedinto veterinary practice in 1937 (Sheppard &Sheppard, 1937; Wright, 1937) and over the next60 years came to be the most widely used inductionagent, especially for dogs and cats. Studies ofits pharmacology did not keep pace with progressin the clinical field and it was not until the 1950sthat any notable contribution to an understandingof its clinical pharmacology was made when Brodieand his co-workers (Brodie, 1952; Brodie et al.,1951; 1953) followed the concentration of the drugin the urine and various body tissues both in dogsand in man. It was found that the liver and plasmaconcentrations of thiopental, which were highalmost immediately after a single injection, soonfell rapidly. The muscle concentration, althoughhigh almost immediately after injection, continuedto rise for some 20 minutes, then fell – the fall beingfairly rapid during the first hour but then becomingprogressively slower in the next two to threehours. In contrast to this, the concentration in thebody fat, which was negligible at first, increasedrapidly during the first hour and then more slowlyuntil a maximum was reached in three to six hours.It was obvious that the concentration in the fat roseat the expense of that in the plasma and all othertissues. Although the brain concentration ofthiopental was below that of the blood plasma,both showed similar changes and therefore thedepth of narcosis could be related to the plasmaconcentration of the drug.From these findings it is clear that the factorswhich govern the duration and depth of narcosisdue to an injection of thiopental are:1. The amount of the drug injected2. The speed of injection3. The rate of distribution of the drug in thenon-fatty tissues of the body4. The rate of uptake of thiopental by the bodyfat.The speed of injection and the quantity injected arerelated. For example, a small amount injected rapidlymay produce a high plasma concentration ofundissociated drug and consequently a parallelhigh brain level so that deep narcosis is inducedrapidly. However, the drug soon becomes distributedthroughout the non-fatty tissues of the bodyso that the plasma concentration and the brainconcentration are reduced and there is a rapiddecrease in the depth of narcosis. In contrast, aslow rate of injection of a larger quantity of thedrug has the effect of maintaining the plasma levelas the drug is distributed to the body tissues. Thismeans that a larger amount of thiopental will benecessary to obtain any given depth of narcosisand recovery will depend more on the uptake ofthe drug by the body fat and detoxication, sincethe concentration of thiopental in the non-fatty tissueswill already be high at the end of injection.Thiopental appears to cross the blood–brainbarrier with very great speed. The factor whichlimits the time of response following an injection isthe circulation time from the site of injection to thebrain. The absence of any appreciable blood–brainbarrier makes the rapid injection of the drug veryuseful for the production of short periods of narcosiswith rapid recovery as redistribution occurs.Induction doses of the drug are usually between5 and 10 mg/kg for most species of animal, but theanaesthetist always aims to combine the effects ofinjection speed and total dose in such a manner asto minimize the quantity needed by any individualfor any given procedure, and takes full advantageof the reduction in dose offered by suitablepremedication.Carbon dioxide (CO 2 ) retention or the administrationof CO 2 has the effect of reducing plasmapH. Alteration of the plasma pH has a complexeffect on the distribution of thiopental in the body.The drug is partially ionized and acts as a weakorganic acid; the dissociation constant is such thata small change in pH will markedly affect the

116 PRINCIPLES AND PROCEDURESdegree of ionization. If the plasma pH is loweredby CO 2 , the undissociated fraction is increased andsince only this fraction is fat soluble, the decreasein pH results in an increase in the uptake of thedrug by fatty tissues. This lowers the plasmaconcentration and narcosis might be expected tolighten. However, this does not occur and Brodiehas suggested that although the total plasmathiopental is reduced, the concentration of theundissociated (active) fraction remains roughlythe same.A further mechanism may be implicated sincethiopental becomes bound to the plasma proteinand the degree of binding depends on the proteinconcentration and the pH of the plasma. Proteinbinding is reduced by a reduction in pH andbecause the pharmacological activity resides in theunbound fraction, narcosis might be expected todeepen when the plasma pH is reduced by CO 2 . Tocomplicate matters further, hyperventilation,which should have the opposite effect to hypercapnia,has been shown to to reduce the amount ofthiopental necessary for the maintenance of anaesthesia.This, of course, is not necessarily contradictorysince all three factors, the uptake by body fat,the degree of dissociaton and the degree of bindingby the plasma proteins, affect the concentrationof active drug. It is unlikely that all threefactors will be affected to the same degree and inthe same way by changes in the pH of the plasma.Comparatively little attention has been given tothe reduction of plasma thiopental concentrationby detoxication. Animal experiments show prolongationof the action of large doses followingliver damage caused by other agents, revealing theimportance of the liver for recovery from thiopental.Mark and co-workers (1963) showed that up to50% of thiopental is removed in its passagethrough the human liver and although there areknown to be marked species variations, metabolismin animals is now generally agreed. In dogs,Saidman and Eger (1966) concluded that althoughthe uptake in muscle still plays the dominant rolein the early fall of arterial thiopental levels, this isrivalled by the additive effect of metabolism anduptake in fat. Decreased liver metabolism was alsoshown to be involved in the prolonged recoveryfrom thiopental found in greyhounds (Ilkiw et al.,1985).After intravenous injection thiopental rapidlyreaches the central nervous system and its effectsbecome apparent within 15–30s of injection.Concentrations of the drug in the plasma and cerebrospinalfluid run parallel so the depth of narcosiscan be assumed to be dependent on, and varywith, the blood level. However, this relationship isnot a simple linear one, as acute tolerance to thedrug develops. The plasma concentration ofthe drug at which the animal wakens increases asthe duration of narcosis proceeds. Moreover, thedepth and duration of narcosis bear some relationto the initial dose. When a large dose has beeninjected for the induction of narcosis, the animalwill awaken at a higher plasma level than after asmall dose. This acute tolerance is probably theexplanation for the clinical observation that recoveryfrom the rapid injection of a given dose isquicker than if the same amount is given slowly.The initial concentration of the drug reaching thebrain is greater when the drug is injected quicklyso that consciousness returns at a higher plasmaconcentration than after a slower administration.In clinical practice the intravenous injection ofthe drug is usually carried out at such a rate thatsurgical anaesthesia is reached within, at the most,1–2 minutes. Apnoea sometimes occurs at a depthof anaesthesia sufficient to permit surgical interventionbut excitement is very rarely seen duringthe induction of anaesthesia. The drug, like all barbiturates,has little, if any, analgesic action andreflex response to stimuli is not abolished until anappreciably greater depth of unconsciousness isreached than is required with many other anaestheticagents. Because of the lack of analgesicproperties anaesthesia is more affected by premedicationwith analgesic drugs than is the case withother anaesthetic agents. This applies also to supplementationduring anaesthesia with analgesicswhether these be of the opioid type (e.g. alfentanil)or analgesic mixtures of nitrous oxide and oxygen.They reduce or abolish reflex response to stimuliand enable operative procedures to be performedat plasma levels of thiopental which would beinsufficient if the drug were given alone.All barbiturate drugs cause respiratory depressionand a short period of apnoea usually followsthe intravenous injection of thiopental. This isprobably due to the central nervous depression

INJECTABLE ANAESTHETIC AGENTS 117caused by the initial high plasma concentration.The sensitivity of the respiratory centre to CO 2 isreduced progressively as narcosis deepens. As aresult of the central depression the alveolar ventilationis diminished, raising the CO 2 tension of thearterial blood.As with many other agents, anaesthesia inhorses is often associated with a peculiar respiratoryeffect – a complete arrest of respiration for20–30 s followed by four to eight respiratory movements.These bursts of activity followed by inactivitymay persist throughout anaesthesia (Longley,1950; Waddington, 1950; Ford, 1951; Jones et al.,1960; Tyagi et al. 1964).There is an apparent increase in the sensitivityof the laryngeal and bronchial reflexes under lightthiopental anaesthesia. This is generally attributedvaguely to parasympathetic preponderance underthiopental anaesthesia. It would be wrong, however,to assume that thiopental itself produceslaryngeal and bronchial spasm for these are reflexphenomena, usually evoked by stimulation of sensoryafferent nerves by small amounts of mucus,regurgitated gastric contents or by foreign bodiessuch as endotracheal tubes. They may also be initiatedby stimuli from other parts of the body.During anaesthesia these reflexes are depressedcentrally and it is probable that thiopental does notaffect the afferent side of the reflex pathway asmuch as other agents do, so that deeper levels ofunconsciousness are necessary for the suppressionof these effects. Certainly, spasm is no more commonin deep thiopental anaesthesia than withother anaesthetic agents.There is considerable disagreement amongresearch workers concerning the effects ofthiopental on the cardiovascular system. This maywell be due to varying methods used for determinationsof such things as cardiac output, differencesof premedication, depth of narcosis and the degreeof CO 2 retention, as well as on the speed of injection.It appears to be generally agreed, however,that the rapid intravenous injection of the drugcauses a fall in blood pressure even in normovolaemicanimals and that this can be serious inhypovolaemic states. After the initial fall in normovolaemicanimals the blood pressure returns toabout the normal level but often with a persistenttachycardia.The drug appears to have a direct depressanteffect on the myocardium and in certain circumstancesmay produce cardiac arrhythmias such asventricular extrasystoles. It is doubtful whetherthese have any clinical significance since they donot seem to progress to fibrillation and usuallypass off spontaneously. In most instances only theECG provides any indication of their presence.Where myocardial damage is present, it is unwiseto use a very rapid rate of injection because thiswill submit the heart to a very high initial concentrationof the drug.In many types of anaemia the amount ofthiopental necessary for any given level of narcosisis reduced, for the plasma protein concentration aswell as the haemoglobin level are low anddecreased protein binding is then responsible forincreased sensitivity to the drug.Thiopental modifies the vasomotor response toincrease in intrathoracic pressure (Valsalvamanoeuvre). In the absence of thiopental, too vigorouscontrolled respiration will produce a fall inarterial pressure by increasing the mean intrathoracicpressure, although a degree of recoveryensues as the result of compensatory venoconstriction.This compensatory mechanism is impairedby thiopental and persistent hypotension mayresult from injudicious positive pressure ventilationof the lungs.Thiopental does not effectively block motornerve impulses and muscular relaxation can beprovided only by excessive central nervousdepression. Shivering is common in all species ofanimal in the recovery period and may be due topersistent cutaneous vasodilatation in a cold environment.It is probably a reflection of the lack ofanalgesic action because it is usually readily controlledby small doses of analgesic drugs.The incidence of hepatic damage is related tothe dose administered and hepatic dysfunctionalways follows the use of large doses. However,the presence of liver damage does not contraindicatethe drug so long as only minimal doses areemployed. Uraemia increases the duration ofthiopental narcosis and the drug should be usedwith care, and in only minimal doses, in uraemicanimals. Renal blood flow varies with the arterialblood pressure and prolonged hypotension causedby thiopental can be followed by temporary

118 PRINCIPLES AND PROCEDURESoliguria. The drug is associated with a small butsometimes persistent fall in plasma potassiumconcentration.Foetal respiration seems particularly sensitiveto the depressant effects of thiopental. It has neverbeen clearly established whether, in animals, along or short induction–delivery interval is beneficialto the offspring. At Cambridge it has beenused as an induction agent for obstetrical cases forover 40 years without evidence of serious harm tothe offspring. Only minimal doses are administeredfor the induction of anaesthesia and a relativelylong induction–delivery interval is allowed.Other induction agents, with the possible exceptionof propofol, and in horses ketamine, appear tohave no remarkable advantages.PresentationIn dogs a 2.5% solution (0.5 g in 20 ml) should beused and 1.25% solution is preferable in very smalldogs and in cats. The intravenous injection of a 5%or stronger solution causes spasm of the vein andperivascular injection causes sloughing of overlyingtissues. The use of a 2.5% solution does notcause venous thrombosis and ensures that accidentalperivascular injection is much less likely tobe followed by tissue necrosis. In small animalswhere the total dose is likely to be between 50 and100 mg, further dilution of the 1.25% solution isadvisable to give the injection bulk and ensure thatthe dose is not given too quickly. When it seemspossible that more than 20 ml of the 2.5 % solutionwill be required for a dog or similar sized animal,thought should be given to the use of suitable premedicationto reduce the thiopental dose.It may be essential to use concentrated solutions(e.g. up to 10%) in horses and the larger farm animalsbut necrosis, sloughing and even aneurysmsmay follow their accidental perivascular injection.The likelihood of accidental perivascular injectionmay be reduced by always injecting the solutionthrough a correctly placed intravenous catheterthat is well secured in position in the vein.It is a remarkable and as yet unexplained factthat the use of a 2.5% rather than a 5% solutionhalves the total dose of the drug which has tobe administered to small animal patients. There isno completely acceptable explanation for thisbut it seems likely that acute tolerance may beinvolved.Thiopental is usually supplied together withthe appropriate quantities of water for injection tomake a 2.5 or 5% solution. When prepared as a2.5% solution dose and stored in multidose vials atroom temperature the solution will generallyremain fit for use for up to four or five days butfreshly prepared 10% solutions may precipitateout at lower environmental temperatures.ContraindicationsPorphyria, a disease characterized by progressiveacute demyelination of nerves, with clinical signsdepending on those most affected, is well documentedin man. In a latent stage any barbituratemay provoke an acute exacerbation. Progressiveparalysis may end in the death of the patient.During these acute excerbations porphobilinogenis usually present in the urine and can be detectedby a simple test in the absence of laboratory facilities.When first voided, urine containing porphobilinogenis usually normal in colour but itdarkens when left standing in daylight for a fewhours. The classic case presents with colickyabdominal pain and many are subjected to unnecessarylaparatomy. Porphyria has been diagnosedin cattle and pigs (Blood & Henderson, 1961) andwhile it is probably of little importance in thesespecies, the anaesthetist must note that it has alsobeen diagnosed in cats (Tobias, 1964) although theexact type of porphyria was uncertain. In the lightof our present knowledge porphyria must be consideredan absolute contraindication to the use ofthiopental in veterinary practice. There are noother absolute contraindications.Thiamylal sodiumThiamylal closely resembles thiopental in chemicalstructure except that while the latter is theethyl derivative of the series, the former is the allylcompound. It is no longer available.METHOHEXITAL SODIUMMethohexital sodium is a racemic mixture of theα-d and a-l isomers of sodium 5-allyl-1-methyl-5-

INJECTABLE ANAESTHETIC AGENTS 119(1-methyl-2-ynyl) barbiturate, and differs fromthiopental in having no sulphur in the molecule. Itis stable for at least six weeks in aqueous solutionskept at room temperature.There are important differences between thisand other barbiturates. The significant featurescharacteristic of methohexital sodium comparedto thiopental are:1. Potency is two or three times greater2. Shorter duration of effect3. More rapid recovery to full alertness, evenafter prolonged anaesthesia (it is the onlybarbiturate drug for which there is convincingevidence of a more rapid recovery thanfrom the ‘standard’ barbiturate, thiopental).Its action is characterized by a rapid induction, satisfactorysurgical anaesthesia and a recoverywhich seldom exceeds 30 minutes. Unfortunately,the recovery period is often complicated by muscletremors or even frank convulsions. Muscletremors may also occur during the inductionof anaesthesia. These undesirable features are usuallysuppressed by the use of an opioid or acepromazinefor premedication. The short duration ofaction depends both on marked fat solubility andalso on rapid hepatic breakdown to inactive compounds.It is best administered to small animals as a 1%solution (10 mg/ml) but when large volumes ofthis solution would be required to administer adose of 3–5 mg/kg, a 2.5% (25 mg/ml) solutionmay be used. In large animals more concentratedsolutions of up to 6% are more convenient. Owingto differences in pH, solutions of methohexitalsodium should not be mixed with acid solutionssuch as atropine sulphate.Rapid injection, especially of the more concentratedsolutions, usually produces apnoea of 30 to60 s duration. Rapid injection may also producetransient hypotension but the blood pressure soonreturns to normal levels. Laryngospasm is reputedto occur less frequently than with the other intravenousanaesthetics.Undoubtedly, there is a place in veterinaryanaesthesia for an agent which can safely producerapid anaesthesia with recovery that is fast andcomplete. Methohexital sodium fulfills mostrequirements, although the occurrence of muscletremors indicates that it is not the perfect agent. Itseems to have an advantage over the thiobarbituratesin that recovery may be completed earlier asthe animal is more alert and coordinated onregaining consciousness. It seems probable, however,that in the near future it will be supersededby propofol and in some countries it is no longeravailable.RAPIDLY ACTINGNON-BARBITURATESSAFFANResearch into the anaesthetic activity of steroidsproduced a number of hypnotic compounds. Ofthese alphaxalone was the most promising and,although virtually insoluble in water, when dissolvedin cremophor EL the addition of anotherweakly hypnotic steroid, alphadolone, increasedits solubility more than threefold. ‘Saffan’ is a mixtureof the two steroids in cremophor EL and thismixture has never been given an ‘official’ name. Inmedical practice an identical formulation wasknown as ‘Althesin’. Solution in cremophor ELbeing no longer acceptable for drugs to be used inman, Althesin was withdrawn from medical clinicaluse in 1984, although many anaesthetists consideredits withdrawal unwarranted.Each millitre of Saffan contains 9 mg of alphaxaloneand 3 mg of alphadolone. The ready-to-usesolution is viscid, has a pH of about 7 and is isotonicwith blood. Like all solutions made up in cremophorEL it froths when drawn up into thesyringe but is miscible with water. The dose ofSaffan may be expressed in several ways but inveterinary anaesthesia it has been usual to recordit as mg (total steroid) per kg body weight.Pharmacological studies in Glaxo laboratories(Child et al., 1971) led to the introduction of Saffanas an anaesthetic for cats, but it can be used in alldomesticated animals, except dogs (in these animalsit causes histamine release), without majorproblems (Hall, 1972; Eales et al., 1974; Eales 1976;Komar, 1984) and in monkeys (Dhiri, 1984).The electroencephalographic pattern of cerebraldepression is similar to that produced by otheranaesthetics. Some evidence has been producedwhich suggests that Saffan selectively decreases

120 PRINCIPLES AND PROCEDUREScerebral oxygen consumption to an extent greaterthan can be attributed to a reduction in cerebralblood flow. Thus, it may be a useful agent foranaesthetizing animals other than dogs sufferingfrom head injuries. When given to cats by intravenousinjection induction is not as smooth as withthiopental and, in the authors’ experience, retchingand even vomiting may occur unless theinduction dose is given rapidly. Twitching of limband facial muscles is also seen but appears to haveno clinical significance. Saffan produces similarfalls in arterial blood pressure, central venouspressure and stroke volume to thiopental, but thehypotension is not dose related and is accompaniedby tachycardia. It causes no significant changesin cardiac index or systemic vascular resistance(Dyson et al., 1987). With moderate doses the arterialhypotension is transient but large doses have amore prolonged effect. Foex and Prys-Roberts(1972) observed a dose-related increase in pulmonaryvascular resistance in goats and concludedthat Saffan appeared to cause a greater fall incardiac output than equipotent doses of otherinduction agents. Sheep appear to be unduly sensitiveto Saffan (Clarke & Hall, 1975) for in theseanimals it produces a marked fall in cardiac output,pulse rate and arterial blood pressure. In dogscremophor EL produces histamine release, thuscausing a further fall in arterial blood pressure andmaking Saffan unsuitable for use without priorantihistamine medication; even then it cannot berecommended.It is claimed that Saffan produces good musclerelaxation in cats without at the same time causingsevere respiratory depression. Malignant hyperthermia-susceptiblepigs have been safely anaesthetizedwith Saffan (Hall et al., 1972).The only endocrine effect of Saffan is a weakanti-oestrogenic action. The major route for excretionof steroids is via the bile and in rats 60–70% ofalphaxalone and alphadolone are excreted by thisroute within three hours of administration. Thereis some evidence that, like progesterone, theanaesthetic steroids are involved in enterohepaticcirculation.Information relating to the transfer of Saffanacross the placental barrier is scanty but clinicalresults show very minor adverse effects on kittenswhen induction doses of up to 6 mg/kg are givento the mother. It has been claimed that kittensbreathe almost immediately after delivery whenthe dose of Saffan given to the mother is restrictedto less than 4 mg/kg.Cats recovering from Saffan anaesthesia oftenshow tremor of muscles, paddle and, if stimulated,may become extremely excited or convulse.Thisexcitement and convulsions disappear as soon asthe stimulation ceases. Oedema and/or hyperaemiaof the ear pinnae and paws is commonunder Saffan anaesthesia. Measurement of pawand ear thickness suggests that this occurs morefrequently than can be recognized by simple visualinspection. Currently, it has to be accepted thatthese side effects result from some idiosyncrasy insome cats to some unidentified ingredient in theproduct. Informed opinion seems to be that thistype of reaction, probably related to histaminerelease, is usually without clinical significance –although there have been occasional reports of earpinna and paw necrosis.Other reports of possible histamine release incats cannot be dismissed so easily. These are clinicalreports, only seldom supported by autopsyfindings, associating the administration of Saffanwith pulmonary oedema. However, in about 30instances, lung oedema has been confirmed histologicallyat autopsy. Evans (1979) attributedpulmonary oedema to an administration oradministrator-related problem because mostreports stem from very few practitioners and heestimated that about 30 000 cats are anaesthetizedwith Saffan each month. There seems to be no wayof preventing it occurring and because it is apotentially lethal problem others take the viewthat Saffan is not an acceptable alternative tothiopental. However, in at least one region of theUK from which pulmonary oedema has beenreported similar trouble has followed the use ofthiopental and this may indicate the operation ofsome factor peculiar to a geographical region. Insuch a region an endemic chronic infection mayprime the complement systems, making them susceptibleto activation by an intravenously administeredcompound. This would lead to histaminerelease in affected animals by the so-called ‘alternativepathway’ without involvement of immunerecognition so no previous exposure to Saffan or toany other intravenous agent would be necessary

INJECTABLE ANAESTHETIC AGENTS 121for such a reaction as histamine-induced pulmonaryoedema to occur. There are also reliablereports of laryngeal oedema following inductionof anaesthesia with Saffan with no history of previousexposure to the steroids.Although all the genus Canis show a doserelatedanaphylactoid type of reaction to surfaceactiveagents such as cremophor EL, a constituentof Saffan, the preparation has been used in dogsafter premedication with acepromazine andchlorpheniramine. Attempts to follow this regimenin dogs in the UK have revealed a high incidenceof skin erythema and vomiting. It isdifficult to accept that the prior administration ofan antihistamine merely to enable Saffan to beused is good practice, especially now that otherand better agents such as propofol are availablefor use in dogs.Unlike many induction agents Saffan may begiven by intramuscular injection but, despite thispossible use, there is no doubt that the prime rolefor the formulation is as an intravenous inductionagent, or as a total anaesthetic (using incrementaldosage or a continuous infusion technique).Metabolism is so fast that subcutaneous injectionfails to produce any evidence of effect on thecentral nervous system, making it possible todisregard inadvertent perivascular injection as faras subsequent doses are concerned.OTHER STEROIDSMinaxoloneFollowing enthusiastic reports of its use in earlyclinical trials in man, minaxolone, a rapidly acting,water soluble steroid was subjected to clinicaltrials involving 70 dogs and six anaesthetists(Clarke & Hall, 1984). It proved to be an adequateanaesthetic, with usually smooth induction butprolonged recovery times. The commonest sideeffect noted was twitching, while the most seriouswas respiratory depression often needing oxygensupplementation coupled with intermittentpositive pressure ventilation of the lungs, to maintainan adequate PaO 2 . Occasionally, there was amarked delay between intravenous injection andthe attainment of maximal anaesthesia. Cardiovasculareffects were minimal, a slight fall in arterialpressure occurring immediately after injection butpressure rapidly returned to normal or slightlyelevated levels.Unfortunately the drug did not live up to expectationswith regard to smoothness of recoveryor speed of recovery and was withdrawn from themarket.5β Pregnanolone and other steroidsThe pregnanes were first reported to possessanaesthetic activity in 1957 but it was a decadelater that the anaesthetic effects of some weredescribed. 5 β Pregnanolone is insoluble in waterbut it has been used as an emulsion in man. To datethere are no published data on its efficacy in veterinaryanaesthesia. It may have an impact on intravenousanaesthetic techniques.METOMIDATEMetomidate (Hypnodil) is a non-barbiturate intravenoushypnotic synthesized in the laboratories ofJanssen Pharmaceutica in Belgium. It was the firstrepresentative of a completely new group ofhypnotics, the imidazole derivatives. It is awhite crystalline powder, freely soluble inwater, but aqueous solutions are unstable andshould be used within 24 hours of preparation.A 1% solution has a pH of 2.9 and a 5% solution apH of 2.4. It was introduced as a hypnotic forpigs and its use has mainly been confined to theseanimals.Metomidate has strong central muscle relaxantproperties but little ability to suppress response topainful stimulation. However, since it has usuallybeen used with other agents, such as fentanyl orazaperone, it is difficult to establish the effects ofthe agent alone. Given by intravenous injection itproduces unconsciousness in one injectionsite–brain circulation time. In pigs, after azaperonepremedication, induction of unconsciousness issmooth and side effects are rarely seen. Occasionallymuscle tremors occur and although theymay persist for a few hours they appear to be oflittle clinical significance. Metomidate has alsobeen given by intraperitoneal injection at the sametime as an intramuscular injection of azaperonebut the results were unpredictable.

122 PRINCIPLES AND PROCEDURESIn pigs, injection of metomidate is followed byslight hypotension, with a decreased pulse rateand a mild decrease in cardiac output. Duringsedation there is remarkable stability of the cardiovascularsystem. Under azaperone–metomidatesedation the minute volume of respiration is equalto that of the rested, conscious pig, with a decreasedfrequency but an increased tidal volume.Piglets delivered by caesarean section from sowsunder metomidate hypnosis are sleepy but usuallyrecover from this depressed state if they are keptwarm. When high doses of metomidate are givento the sow the piglets may show tremors for severalhours after birth.Although introduced as a hypnotic for pigs ithas also been used experimentally in horses (Cox,1973; Hillidge et al., 1973) and for restraint for avariety of species of birds (Cooper, 1974). In horsesmetomidate produces sweating, muscular tremorsand involuntary head and limb movements ; itcannot be recommended for clinical use.RoleAlthough possibly indicated for pigs, there is currentlylittle call for its use in the field because offarm economics and although pigs are becomingwidely used as experimental animals other agentsare usually more satisfactory for laboratorypurposes.ETOMIDATEThe commercial preparation, Hypnomidate, contains20 mg of the dextrorotatory isomer of thecompound dissolved in 10 ml of a mixture of 35%propylene glycol and 65% water v/v, becauseinjection of plain aqueous solutions causes pain.Etomidate is currently much more expensive thanmetomidate.The pharmacokinetics of etomidate favour itsuse as an infusion and, combined with its low cardiovasculartoxicity it is not surprising that thisbecame a popular technique (usually combinedwith an opioid such as fentanyl) in man. In dogs itis 76% bound to albumin and like thiopental itquickly enters the brain and leaves rapidly as itbecomes redistributed in the body. Of the totaldose given, in rats 83% is excreted in the urine in24 hours (2% as unchanged etomidate) and 13% isexcreted in the bile. It is quickly hydrolysed byesterases in the liver and plasma to pharmacologicallyinert metabolites. The pharmacokinetics ofetomidate in cats have been investigated (Wertzet al., 1990) and are best described by a threecompartmentopen model similar to those determinedin people and rats.In effective doses etomidate causes loss of consciousnessin one injection site–brain circulationtime and in dogs doses of 1.5 to 3 mg/kg producehypnosis, in a dose dependent manner, lastingfrom 10 to 20 minutes. Thus on a weight-forweightbasis it appears to be about 10 times morepotent than thiopental. Side effects are no morelikely to occur with the higher dose rates than withlower ones.Intravenous injection is associated with a highincidence of involuntary muscle movement,tremor and hypertonus. The EEG changes producedby etomidate at induction are similar tothose seen with barbiturates and no specificepileptogenic or convulsive activity is observed, sothe muscle movements cannot be attributed tocentral nervous activity. Premedication withdiazepam, fentanyl or pethidine reduces the incidenceof these side effects so they may be related topain on intravenous injection when the drug isadministered through a small calibre vein.Lack of cardiovascular depression is claimed tobe one of the outstanding features of etomidate(Nagel et al., 1979). The drug does release significantamounts of histamine and there is a very lowincidence of thrombosis after injection. Injection ofetomidate is frequently followed by a short bout ofcoughing in unpremedicated dogs but in generalrespiration is less depressed than after other intravenoushypnotics.A slight rise in serum potassium occurs whenmarked, persistent myoclonic movements occur,but the main effect of importance is that etomidateinhibits increases in plasma cortisol and aldosteroneconcentrations during surgical stress, evenwhen adrenocorticotropic hormone levels arenormal or increased. In canine surgical patientsadrenocortical function is suppressed for two tothree hours after the administration of etomidate(Kruse-Elliott et al., 1987). Suppression of theendocrine response to surgical stress has been

INJECTABLE ANAESTHETIC AGENTS 123deemed by some to be beneficial, although thissuppression has resulted in etomidate no longerbeing used for sedation of human patients inintensive care units.RoleIt is impossible to assess whether etomidate has aplace in veterinary anaesthesia. Erhardt (1984) hasreported acceptable results with a mixture of etomidateand alfentanil mixed in a ratio of 1.000 mgto 0.015 mg in dogs, cats, rats, rabbits, sheep, goatsand calves but etomidate has so far failed to makeany impact in veterinary practice in NorthAmerica or the UK.EUGENOLSThe eugenols are related to oil of cloves and threederivatives have been subjected to clinical trials inman. The first, known as G29505 or Estil, wasabandoned because of its deleterious effects onveins. Another derivative, Propinal, was abandonedvery quickly because of its effects on respirationand the circulation. The third eugenol,propanidid (Epontol), became available in the UKin 1967. Doses of 5 mg/kg given to very smallponies by extremely rapid intravenous injectionproduced anaesthesia sufficient for castration followedby complete recovery in less than 10 minutes.Because of the extremely short duration ofaction it was found to be physically impossible togive the drug fast enough to produce anaesthesiain larger horses, and violent excitement followedthe administration of subanaesthetic doses. Indogs, Epontol was found to produce profoundhypotension, probably because propanidid wasdissolved in cremophor EL.PROPOFOLPropofol is an intravenous anaesthetic agentunrelated to barbiturates, eugenols, or steroidanaesthetic agents. The active ingredient, 2,6 diisopropylphenol,exists as an oil at room temperatures.Originally introduced in a preparationcontaining the surface-active agent cremophor ELit is now presented as a free flowing oil-in-wateremulsion containing 1% w/v soya bean oil, 1.2%w/v purified egg phosphatide and 2.25% w/vglycerol.Like thiopental, propofol is a rapidly-actingagent producing anaesthesia of short durationwithout side effects. Both agents produce equivalentcardiovascular and respiratory effects but,unlike thiopental, propofol does not damagetissue when injected perivascularly or intra-arterially.Pain on injection into small veins has beenreported in man and occasionally dogs seem toresent injection into the cephalic vein. The reasonfor pain on injection is not known but the variouspossible explanations have been reviewed by Tan& Onsiong (1998). Greater reflex depression andmore pronounced EEG changes are associatedwith propofol than with thiopental.Details of pharmacological studies performedin rabbits, cats, pigs and monkeys were published(Glen, 1980; James & Glen, 1980; Glen & Hunter,1984), and preliminary clinical trials in 10 dogs andone cat soon followed (Hall, 1984). Propofol hasbeen shown to be compatible with a wide range ofdrugs used for premedication, inhalation anaesthesiaand neuromuscular block (James & Glen,1980). It lacks any central anticholinergic effect, isnot potentiated by other non-anaesthetic drugs,does not affect bronchomotor tone or gastrointestinalmotility, and decreases the risk for catecholamineinduced cardiac arrhythmias.The propofol blood concentration profile followinga single bolus dose can be described by thesum of three exponential functions representing;(i) distribution from blood into tissues(ii) metabolic clearance from blood(iii) metabolic clearance constrained by theslow return of propofol into the blood from apoorly perfused tissue compartment.It is highly lipophilic and rapidly metabolizedprimarily to inactive glucuronide conjugates, themetabolites being excreted in the urine. In man,liver disease and renal failure have little effect onpharmacokinetic parameters and it seems likelythat extrahepatic mechanisms contribute to themetabolism of propofol, but this has not beeninvestigated in any detail in other animals. In dogspremedication with 10 µg/kg of medetomidine,which might be expected to reduce hepatic bloodflow, does not significantly alter the kinetic

124 PRINCIPLES AND PROCEDURESTABLE 5.1 Mean utilization rate of propofol (datasupplied by J.B.Glen)SpeciesMean utilization rate(mg/kg/min)Mouse 2.22Rabbit 1.55Rat 0.61Pig 0.28Cat 0.19TABLE 5.2 Disposition of propofol in mongrel andlaboratory beagle dogs. V SS = apparent volume ofdistribution at steady state.T 1/2 β = eliminationhalf-life. * indicates a significant difference atp > 0.05 (data from Hall et al.,1994;1997);Disposition Mongrel dogs Laboratorybeagles(n = 6) (n = 6)V SS (L/kg) 6.04 (0.71) 3.27 (0.26)*Systemicclearance 34.40 (1.92) 47.46 (6.21)(ml/kg/min)T 1/2β (min) 486.2 (56.4) 131.30 (12.82)*variables (Hall et al., 1994). In cats considerablefirst pass extraction of propofol occurs in the lung(Matot et al., 1993) and it is uncertain whether all ofthe drug is released back into the circulation or ifsome is metabolized in the pulmonary tissue.The mean ‘utilization rate’ of propofol variesfrom species to species (Table 5.1) and is probablyrelated to differences in the rate of biotransformationand conjugation as the cat, with the smallestutilization rate of the animals studied, has a deficiencyin its ability to conjugate phenols.Propofol is now accepted as a most useful agentin all domestic animals, although its current priceprecludes its widespread use in adult farm animalsand horses. The principal advantage of propofolover thiopental is the more rapid recovery of consciousness.As it is very lipophilic it has a very largevolume of distribution. There are noticeable differencesbetween the disposition data from mongrelsand beagle dogs (Table 5.2). It is metabolized veryquickly although, at least in man, concurrentadministration of fentanyl reduces clearance andincreases plasma concentrations (Cockshott, 1985).The dose for induction of anaesthesia inunpremedicated dogs and cats is between 6 and7 mg/kg. Premedication with between 0.02 and0.04 mg/kg of acepromazine reduces this inductiondose by about 30% in dogs but this effect is notso marked in cats premedicated with 0.04 mg/kgof acepromazine (Brearley et al., 1988). Premedicationwith 10 or 20 µg/kg of medetomidinedecreases the anaesthetic induction dose in dogs toabout 5 mg/kg and 3 mg/kg respectively (Hallet al., 1994; 1997). Blood systemic clearance isalmost halved by premedication with medetomidine20 µg/kg whereas 10 µg/kg produces very littleeffect. It has been demonstrated that thepharmacokinetics of propofol differ in greyhoundsand mixed breed dogs (Zoran & Riedesel,1993) so that breed differences must be expected.In dogs, anaesthesia maintained by continuousinfusion (Chambers, 1988; Vainio 1991; Nolan &Reid, 1993; Hammond & England, 1994) appearedto be less controllable than that maintained byhalothane/nitrous oxide (Hall & Chambers, 1987;Chambers, 1988) although it is perhaps betterwhen maintained by intermittent injections of theagent (Watkins et al., 1987). Following a singleintravenous dose of 6 mg/kg recovery in dogs iscomplete (awake, no ataxia) after about 20 minutesand neither acepromazine nor medetomidine premedicationappear to increase the recovery time.Recovery in greyhounds and other sighthounds isno longer than in other breeds. There is a suggestionthat some families of boxer dogs may be moresusceptible to the drug since recovery was prolongedin some related animals of this breed (Hall& Chambers, 1987). In cats recovery after a singledose is less rapid – about 30 minutes – presumablybecause of relative inability to conjugate phenols.In cats the incidence of postanaesthetic side effectssuch as vomiting/retching and sneezing or pawingat the mouth is about 15% but this can beslightly reduced by acepromazine premedication(Brearley et al., 1988). Vomiting and retchingmay also be seen during recovery in dogs, the incidencebeing about 16% following infusion at0.4mg/kg/min after atropine and acepromazinepremedication (Chambers, 1988).Propofol has also been used for anaesthesia inhorses (Nolan, 1982; Nolan & Hall, 1985; Aguiaret al., 1993), goats (Nolan et al., 1991), macacaque

INJECTABLE ANAESTHETIC AGENTS 125monkeys (Sainsbury et al., 1991) and many otherspecies of animal. It does not appear to triggermalignant hyperthermia in susceptible pigs (Raff& Harrison, 1989)The great attraction for using propofol is therapid and complete, excitement-free awakening,irrespective of the duration of anaesthesia. However,animals require careful observation duringthe recovery period to ensure that they come to noharm from vomiting. In dogs, excitatory phenomenaassociated with the use of propofol have beenreported (Davies, 1991; Davies & Hall, 1991).These have been mainly muscle twitching, extensorrigidity and opisthotonus, and have not givenrise to life-threatening situations.LESS RAPIDLY ACTING INTRAVENOUSAGENTSThe less rapidly acting intravenous agents includechloral hydrate, the dissociative agents and pentobarbitalsodium. In the past all have been used asanaesthetics but appropriate doses do not produceunconsciousness in one injection site–brain circulationtime.CHLORAL HYDRATEChloral hydrate is a white, translucent, crystallinesubstance which volatilizes on exposure to air,producing a penetrating smell. It is not deliquescent,but it is readily soluble in water and aqueoussolutions are generally stable although the drugdecomposes in the presence of alkali. Solutionsmay be sterilized by boiling for a few minutes. Inthe blood chloral hydrate is reduced to 2,2,2-trichloroethanol and its narcotic effect is generallyattributed to this substance. When given by intravenousinjection its effects are slow in appearingand this means that it is difficult to assess thedegree of depression produced by a given dose asinjection proceeds. Even following slow intravenousinfusion of a dilute solution, narcosis continuesto deepen for several minutes andadditional doses should not be administered untilit is clear that the maximum depth of depressionfrom the initial dose has been reached. Perivascularinjection causes severe tissue reaction,often followed by sloughing of the overlyingtissues. A small amount appears unchanged in theurine but most is excreted after conjugationwith glycuronic acid through the kidneys astrichloroethylglycuronic acid.Chloral hydrate is a hypnotic and not an anaesthetic.The dose needed to produce anaesthesia isvery close to the minimal lethal dose. It has onlyvery weak analgesic action. Hypnotic doses causerespiratory depression and large doses result inarterial hypotension. Death from chloral hydrateresults as a result of respiratory depression.The drug was never used as an anaesthetic indogs and cats but formerly it was used extensivelyin large animals, sometimes with a barbiturate(Wright, 1957). Recovery from chloral hydrateanaesthesia in horses occupies one to four or morehours and unless tranquillizers are given is oftenaccompanied by struggling to rise. Its action incattle is similar to that in horses except that recoveryis always quiet. It was often given, well dilutedwith water, by stomach tube into the rumen. Morerecently introduced agents are safer and more convenientto administer to both horses and cattle andthere is little to recommend its continuing use.CHLORALOSEChloralose is prepared by heating equal quantitiesof glucose and chloral hydrate under controlledconditions so that two isomers are produced. Onlyα-chloralose has narcotic properties; β chloralosecan produce muscular pain. α-Chloralose is availablecommercially as a white, crystalline powderand it is used as a 1% solution in water or saline.The solution is prepared fresh immediately beforeuse by heating to 60°C. Heating above this temperatureresults in decomposition and precipitationoccurs on standing. Chloralose is still extensivelyused in physiological and pharmacological nonsurvivalexperiments. Because large volumes ofsolution have to be given before consciousness islost, anaesthesia is often induced with some otheragent such as methohexital or, today, propofol. Anintravenous dose of 80–100 mg/kg of chloralosecauses loss of consciousness but spontaneousmuscular activity is common. The peak narcoticaction of chloralose is seen some 15 to 20 minutesafter injection. The arterial blood pressure is elev-

126 PRINCIPLES AND PROCEDURESated and the activity of the autonomic nervoussystem is believed to be unaffected. The heart rateis often greatly increased and respiratory depressiondoes not occur until very large doses aregiven. In the body chloralose is broken down tochloral and glucose and the safety margin is relativelywide.Disadvantages are its relative insolubility, thelong comparatively shallow depth of anaesthesiaand the slow recovery accompanied by struggling.It has no place in veterinary practice but it isregarded by many experimentalists as a valuabledrug for maintenance of unconsciousness for long,non-survival experiments.URETHANEUrethane is no longer commonly used as an anaestheticfor any laboratory experiments. It wasoften given with chloralose to suppress the muscularactivity which may occur when chloralose isused alone. Urethane has little effect on respirationand arterial blood pressure. It is believed to be carcinogenicand laboratory workers still having contactwith this compound should handle it withcare.PENTOBARBITAL SODIUMPentobarbital sodium in the form of a racemicmixture of sodium 5-ethyl-5-(1-methylbutyl) barbiturateis marketed as a sterile 6.5% solution containingpropylene glycol, as a powder in gelatinecapsules and, for euthanasia, in non-sterile solutionsof about 20%.The main action of pentobarbital sodium is todepress the central nervous system, and effectsupon other systems of the body only becomeimportant as the toxic limitations to the use of thedrug are approached. It depresses the cerebral cortexand, probably, the hypothalamus. Because itdepresses the motor areas of the brain it is used tocontrol convulsive seizures. It has only a weakanalgesic action and relatively large doses must beadministered before pain perception is affected;like all barbiturates, it is primarily a hypnoticdrug. Pentobarbital sodium takes an appreciabletime to cross the blood–brain barrier and whengiven by intravenous injection the rate of injectionmust be slow if the full effects are to be assessed asinjection proceeds.The drug markedly depressesthe respiratory centre and in pregnant animals itdiffuses readily across the placenta into the fetalcirculation, inhibiting fetal respiratory movements.One of its isomers causes a transient periodof excitement before depressing the central nervoussystem while the other produces smoother,progressive hypnosis.In sheep, pentobarbital causes a marked decreasein stroke volume and in the acceleration ofblood in the pulmonary artery. Pulse rate increasesbut this does not compensate for the fall in strokevolume so cardiac output falls to an average of64% of the resting volume in the conscious animal(Clarke & Hall, 1975). The blood pressure maysubsequently rise due to hypercapnia consequentupon respiratory depression produced by thedrug. The drug alters both myocardial functionand the distribution of blood flow in most laboratoryanimals so that although often used in thepast as an anaesthetic for physiological and pharmacologicalstudies their results require criticalevaluation.The drug has no appreciable effect on the gastrointestinalsystem or on liver function but largedoses may cause further damage to an alreadydamaged liver. It is destroyed primarily in the liveralthough other tissues may have the power ofbreaking it down. Some of the administered dose isexcreted in the urine so that if a diuresis can be producedby intravenous infusion of fluid, awakeningmay be accelerated. Pentobarbital has no directaction on the kidney but may inhibit water diuresis,probably by causing a release of antidiuretichormone from the pituitary gland (Blake, 1957).Recovery from pentobarbital is always slow butthe duration varies according to the species of animal.The drug is metabolized more rapidly inhorses, sheep and goats than in pigs, dogs andcats. Convulsive movements, paddling and vocalizationmay occur in the recovery period but suchexcitatory phenomena can usually be suppressedwith analgesics or tranquillizers although thesewill further delay complete recovery. The ‘glucoseeffect’ – a reanaesthetizing effect due to a glucoseinduced decreased microsomal activity – exhibits amarked species variability and is of no significancein dogs, cats, mice or rats, although it has been

INJECTABLE ANAESTHETIC AGENTS 127demonstrated to prolong recovery in rabbits andguinea pigs (Hamlin et al., 1965).RoleIn horses pentobarbital may be used to prolong theduration of chloral hydrate hypnosis. Horsesmetabolize pentobarbital relatively quickly butunless combined with chloral hydrate recovery isusually associated with excitement. Sheep andgoats also metabolize the drug rapidly. In the fieldit may used in cattle for anaesthesia of short duration,although the prolonged recovery period constitutesa disadvantage. In dogs and cats it can beused on its own as a hypnotic or anaesthetic butanalgesics are needed to reduce distress in recoveryafter surgery. In the laboratory it is still a mostwidely used injectable anaesthetic in dogs and catsdespite its disadvantages. It is becoming increasinglyused to maintain hypnosis in pigs for long,non-survival experiments.DISSOCIATIVE AGENTSThree cyclohexylamine derivatives have beenused in several species of animal to produce a statethat enables a surgical operation to be carried out.These substances, phencyclidine, tiletamine andketamine, differ markedly both in chemical andphysical properties as well as in their clinicaleffects when compared to the non-inhalationagents already described. They have been describedas having cataleptic, analgesic and anaestheticaction, but no hypnotic properties.Catalepsy is defined as a characteristic akineticstate with loss of orthostatic reflexes but withoutimpairment of consciousness in which the extremitiesappear to be paralysed by motor and sensoryfailure.Another definition of the state produced bythese agents is ‘dissociative anaesthesia’ which ischaracterized by complete analgesia combinedwith only superficial sleep. In man, hallucinationsand emergence delirium phenomena are known tooccur. It cannot be established whether similarphenomena are experienced by animals but thestate produced by these substances is clinicallyvery different from anaesthesia produced by otheragents. Spontaneous involuntary muscle movementand hypertonus are not uncommon duringinduction and purposeless tonic-clonic movementsof the extremities may be mistaken to indicatean inadequate level of anaesthesia and the needfor additional doses and unless this possibility isrecognized, overdoses may be given.Electroencephalographic studies show a functionaldissociation between the thalamoneocorticaland limbic systems, the former beingdepressed before there is a significant effect on thereticular activating and limbic systems.This differsfrom the effects of other non-inhalation anaestheticsand is manifested by the state of the animal.Hypertonus and muscle movement have alreadybeen mentioned; in addition animals may remainwith their eyes open and have a good tone in thejaw muscles with active laryngeal and pharyngealreflexes, whilst analgesia appears to be extremelygood.PhencyclidinePhencyclidine was the first dissociative agent usedin veterinary anaesthesia but is no longer generallyavailable.TiletamineTiletamine hydrochloride is a cataleptic agent similarto phencyclidine hydrochloride but at leasttwice as potent. The lack of muscle relaxation andlong recovery period together with pain on injectionof the available preparation (Garmer, 1969)resulted in it not being used in the UK.TILETAMINE-ZOLAZEPAM MIXTURETiletamine is currently marketed in combinationwith a diazepam analogue, zolazepam (‘Telazol’,‘Zoletil’) in the USA, Australia, Europe and elsewhere,but not in the UK. This preparation is a 1:1dry powder with a long shelf-life. It can be madeinto highly concentrated solutions convenient foradministration to wild animals by dart gun.In domestic cats the drug combination causestachycardia with slight rises in blood pressure andcardiac output coupled with initial respiratorystimulation followed by mild depression of

128 PRINCIPLES AND PROCEDURESbreathing. Its use in non-domesticated cats hasbeen well described by Lewis (1994). In dogs, thetranquillizing effects of zolazepam seem to wanebefore those of tiletamine so that recovery is oftenviolent. Muscle rigidity is common and someseizure-like manifestations may be seen. In the UKthe mixture has yet to be subjected to clinical trialsbut initial reports indicate that the combination isunlikely to find favour.KETAMINEThe ketamine molecule exists as two optical isomersand the racemic mixture is currently usedclinically. It is available in 10, 50 and 100 mg/mlstrengths suitable for i.m. or i.v. injection. The10mg/ml solution is made isotonic with sodiumchloride. In all species of animal ketamine appearsto have a much shorter duration of action thanphencyclidine or tiletamine.The effects of the two enantiomers of ketaminediffer. The potency ratio between the two isomersappears to be greater for ketamine’s analgesicaction than for its anaesthetic effect. White et al.(1980) have suggested that d-ketamine (about fourtimes as potent than the l form) would be moreuseful than either the racemic mixture or the l isomer,retaining the desirable but lacking the undesirableproperties of the drug. It is unlikely thatthis will be followed up because it would involveconsiderable pharmaceutical outlay, which mighthave been very much more worthwhile if it hadpreceded the introduction of propofol.The effects of ketamine on the central nervoussystem become apparent rapidly for the brain/plasma ratio becomes constant in less than oneminute. It also rapidly crosses the placental barrier.Liver metabolism produces at least four metaboliteswhich are excreted in the urine; they mayhave some slight additive effect to the action of theparent drug. Ketamine produces profound analgesiawithout muscle relaxtion, and tonic-clonicspasms of limb muscles may occur even in theabsence of surgical or other stimulation. Salivationis increased and saliva can obstruct the airwayeven though laryngeal and pharyngeal reflexes areretained. To eliminate side effects a variety of othercompounds such as atropine, diazepam, midazolam,xylazine, detomidine, medetomidine andeven the thiobarbiturates or an inhalation agentare commonly given concurrently with ketamine.Mild respiratory depression has been reportedand in clinical practice this is usually manifestedby an increased rate which does not compensatefor a decreased tidal volume. Although laryngealreflexes may be present it is still necessary for theairway to be kept under close observation becausethe degree of protection of the upper airway is lessthan was once thought.In contrast with the action of other i.v. inductionagents ketamine causes a rise in arterial bloodpressure. The rate of injection is not an importantfactor in the production of hypertension and i.m.injection results in no less a rise in blood pressurethan the i.v. route. The picture is one of stimulationby an agent which has a direct depressant actionon the isolated heart preparation. This is probablydue to an increase in circulating catecholaminescaused by ketamine blocking the reuptake of noradrenalineby adrenergic nerve terminals. Cardiacarrhythmias are uncommon in animals under ketamineanaesthesia and the minimal arterial bloodpressure is always similar to and rarely less thanthe preoperative level.Ketamine produces little, if any, muscle relaxation.There is generally an increase in skeletalmuscle tonus and tendon reflexes are brisk.Athetoid limb movements occur without externalstimuli and are not dose-related.There is no evidence of tolerance developingafter repeated injections of ketamine and no significantcumulative effects have been reported in theveterinary literature, although a case of tolerancehas been noted in a young child (Stevens & Hain,1981). Daily injections of ketamine in rats, dogsand monkeys caused no alterations in haematological,urine or bone marrow values or in bloodchemistry. According to the manufacturers therewere no adverse effects on the dam or the pupswhen pregnant bitches were given 25 mg/kg ketaminetwice a week over a three-week period duringeach third of pregnancy and pregnant rabbitsgiven ketamine daily during the period of organogenesisproduced normal litters.There is little published information regardingthe use of ketamine for caesarian section in anyspecies of animal. In the authors’ experience lambsdelivered from ewes that have had anaesthesia

INJECTABLE ANAESTHETIC AGENTS 129induced with ketamine behave as though they areunaware of their surroundings for up to 12 hoursafter delivery. Extreme difficulty was experiencedin getting them to suckle in the first six hours oflife. The behaviour of young of other animalspecies born to mothers after ketamine has apparentlynot been studied but for caesarian section inmares, induction of anaesthesia with ketamineafter xylazine premedication seems to have littleeffect on the survival of the foal.The difficulty in assessing the depth of unconsciousnesscoupled with the poor muscle relaxationproduced by the drug make it doubtfulwhether ketamine should ever be used alone forsurgical operations, although its ease of administrationmakes its use superficially attractive in animalssuch as sheep and cats. Ketamine alone insheep, or in any other animals, in the authors’experience and that of others (Taylor et al., 1972;Thurmon et al., 1973) fails to produce satisfactoryanaesthesia. In cats it is doubtful if ketamine aloneshould be used, except possibly to subdue a particularlywild individual. However, there is generalagreement that if injectables have to be used, ketamineis the agent of choice for the sedation ofreptiles (Bree & Gross, 1969; Borzio,1973; Harding,1977). Similarly, ketamine has proved to be ofvalue in many species of birds (Gerlach, 1969;Kittle, 1971; Mattingly, 1972; Klide, 1973;Mandelker, 1973; Boever & Wright, 1975) wheninhalation agents are unavailable.REFERENCESAguiar, A.J.A., Hussni, C.A., Luna, S.P.L., Castro, G.B.,Massone, F. and Alves, A.L.G. (1993) Propofolcompared with propofol/guaiphenesin afterdetomidine premedication for equine surgery. Journalof Veterinary Anaesthesia 20: 26–28.Blake, W.D. (1957) Some effects of pentobarbital andanesthesia on renal hemodynamics. American Journalof Physiology 191: 393–398.Blood, D.C. and Henderson, J.A. (1961). In: VeterinaryMedicine. London: Baillière, Tindall and Cox.Boever, W.J. and Wright, W. (1975). Use of ketamine forrestraint and anaesthesia of birds. Veterinary Medicine– Small Animal Clinician 70: 86–88.Borzio, F. (1973) Ketamine hydrochloride as ananesthetic for wild fowl. Veterinary Medicine – SmallAnimal Clinician 68: 1364–1367.Brearley, J.C., Kellagher, R.E.B. and Hall, L.W. (1988)Propofol anaesthesia in cats. Journal of Small AnimalPractice 29: 315–322.Bree, M.M. and Gross, N.B. (1969). Anesthesia of pigeonswith CI581 (ketamine) and pentobarbital. LaboratoryAnimal Care 19: 500–502.Brodie, B.B. (1952). Physiological disposition andchemical fate of thiobarbiturates in the body. FederalProceedings 11: 632–639.Brodie, B.B., Mark, L. C., Papper, E.M., Lief, P.A.,Bernstein, E. and Papper, E.M. (1951). Acute toleranceto thiopentone.Journal of Pharmacology andExperimental Therapeutics 102: 215–218.Brodie, B.B, Burns, J.J., Mark, L.C., Lief, P.A.,Bernstein,E. and Papper, E.M. (1953). Fate ofpentobarbital in man and dog, and method for itsestimation in biological material. Journal ofPharmacology and Experimental Therapeutics109: 26–34.Chambers, J.P. (1988). Propofol infusion anaesthesia indogs. Journal of the Association of VeterinaryAnaesthetists 15: 135.Child, K.J., Currie, J.P., Davis, B., Dodds, M.G., Pearce,D.R. and Twissell, D.J. (1971). The pharmacologicalproperties in animals of CT1341 – a new steroidanaesthetic agent. British Journal of Anaesthesia 43:2–13.Clarke, K.W. and Hall, L.W. (1975). The effect of someintravenous anaesthetics on cardiac output.Proceedings of the 20th. World VeterinaryCongress,Thessaloniki. 2: 1688–1692 (published in 1976).Clarke, K.W. and Hall, L.W. (1984). Minaxolone : aclinical trial in the dog. Journal of the Association ofVeterinary Anaesthetists 12: 83–92.Cockshott, I.D. (1985). Propofol (‘Diprivan’)pharmacokinetics and metabolism – an overview.Postgraduate Medical Journal., 61 (Suppl 13): 45–50.Cooper, J.E. (1974). Metomidate anaesthesia of somebirds of prey for laparotomy and sexing. VeterinaryRecord 94: 437–440.Cox, J.E. (1973). Immobilization and anaesthesia of thepig. Veterinary Record 92: 143–147.Davies, C. (1991). Excitatory phenomena following theuse of propofol in dogs. Journal of VeterinaryAnaesthesia 18: 48–51.Davies, C. and Hall, L.W. (1991). Propofol and excitatorysequelae in dogs. Anaesthesia 46: 797–798.Dhiri, A.K. (1984). Continuous intravenous infusionusing Saffan (CT1341) in the Patas monkey. Journal ofthe Association of Veterinary Anaesthetists of Great Britainand Ireland 12: 68–77.Dundee, J.W. and Wyant, G.M. (1988) In: IntravenousAnaesthesia 2nd Edition, Edinburgh. ChurchillLivingstone.Dyson, D.H., Allen, D.A., Ingwersen, W., Pascoe, P.J. andO’Grady, M. (1987). Efects of Saffan oncardiopulmonary functions in healthy cats. CanadianJournal of Veterinary Research 51: 236–239.Eales, F.A., Hall, L.W. and Massey G.M. (1974)‘Saffan’ a new steroid anaesthetic in veterinary

130 PRINCIPLES AND PROCEDURESanaesthesia. Proceedings of the Association of VeterinaryAnaesthetists of Great Britain and Ireland. No. 5: 1–5.Eales, F.A. (1976). Effects of Saffan administeredintravenously in the horse. Veterinary Record99: 270–272.Erhardt, W. (1984). Anaesthesia with alfentanil andetomidate in several animal species. Journal of theAssociation of Veterinary Anaesthetists of Great Britainand Ireland 12: 196–196.Evans, J.M. (1979). Steroid anaesthesia five years on.Proceedings of the Association of Veterinary Anaesthetistsof Great Britain and Ireland 8: 73–84.Foex, P. and Prys-Roberts, C. (1972). Pulmonaryhaemodynamics and myocardial effects of Althesin(CT1341) in goat. Postgraduate Medical Journal.(Suppl 2). 48–24.Ford, E.J.H. (1951) Some observations on the use ofthiopentone in large animals. Veterinary Record63: 636–638.Garmer, L.N. (1969). Effects of 2-ethylamino- 2’-(2’phenyl) cyclohexanone HCl (CI-634) in cats.Research in Veterinary Science 10: 382–388.Gerlach, H. 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General pharmacology of the6inhalation anaestheticsINTRODUCTIONAn inhalation anaesthetic cannot be introduced intothe brain without at the same time being distributedthrough the entire body, and this distribution exertsa controlling influence over the rate of uptake orelimination of the anaesthetic by brain tissue. Sofar, no specific receptors mediating the actions ofused inhalation anaesthetics have been identified.It seems that they act via a non-specific (? physical)mechanism on the lipid bilayer of cell membranesand thus it is not unexpected that profound effectson other organ systems besides the central nervoussystem have been readily identified.The influence of the physical characteristicsshown in Table 6.1 on the pharmacokinetics of thevolatile anaesthetic agents (and therefore on thespeed on induction of and recovery from anaesthesia)have been described in detail in Chapter 3. Theanaesthetist needs to know these and other physicaland pharmacodynamic properties of the currentlyused inhalation agents in order to use theseagents in the safest possible manner.NON-INFLAMMABILITYModern anaesthetics must be non-inflammable inthe range of concentrations and in the range of gasmixtures (usually of O 2 and N 2 O) used in clinicalpractice. In the past, quenching gases such ashelium were used to make otherwise explosivemixtures of agents such as cyclopropane safe forTABLE 6.1 Physical characteristics for some anaesthetic agents. Values taken from various sources inthe literature but mainly from Halsey (1981),Steward et al.(1900),Eger (1987),Rhône Mèrieux datasheets and Ohio Medical ProductsCompound Water/gas Blood/gas Oil/gas Boiling Point (°C) Vapour Pressurepart.coeff. part.coeff. part.coeff. at 20°C.(mmHG)Cyclopropane 0.21 0.55 11.50 –34.0 Gas at 20 °CDesflurane 0.23 0.42 18.70 23.5 664Enflurane 0.78 1.90 98.00 56.5 172Ether 13.00 12.00 65.00 34.6 442Halothane 0.80 1.94 220.00 50.2 240Isoflurane 0.62 1.40 97.00 48.5 236Methoxyflurane 12.00 970.00 104.8 23Nitrous oxide 0.47 0.47 1.40 –89.0 Gas at 20 °CSevoflurane 0.36 0.60 53.00 58.5 157133

134 PRINCIPLES AND PROCEDURESclinical purposes but today non-inflammability isusually achieved by halogenation – in particularfluorination – of the agent. In most cases this doesnot greatly change inflammability limits but itdoes greatly increase the energy necessary toignite the agents and it is this which renders theseagents non-inflammable in clinical use. Theyrequire a spark having an energy of 10–30 joules toignite them and a static spark released within ananaesthetic system has an energy of only a fewhundred millijoules. Thus, the halothane/oxygenmixture within the vaporizing chamber of aplenum type vaporizer (see p.67) may containabout 33% of halothane at 20 °C, well within theflammable range for halothane, but it could onlybe ignited by a powerful energy source which cannotbe present during normal use.Promising anaesthetic agents have often beenrejected on grounds of inflammability and it isworth noting that N 2 O increases the flammabilityof organic vapours because it is an endothermiccompound whose decomposition results in theevolution of heat together with the production ofan oxygen-rich mixture (33% O 2 ). Thus, althoughthe lowest concentration of halothane in oxygenwhich can be ignited is around 14% it can beshown that in pure N 2 O, 2% of halothane vapouris ignitable by an ignition energy as low as 0.3joules.CHEMICAL STABILITYThe use of completely closed breathing systems(see p.68) imposes a severe test on the chemical stabilityof an agent because of its continuing passageover hot, moist CO 2 absorbents (soda lime orBarolyme). A compound which is toxic to mice inthe concentration range of 100–5000 ppm has beendetected after one hour of closed circuit halothaneanaesthesia (Sharp et al., 1979) but halothane hasnow been used very extensively with soda limecarbon dioxide absorption during prolongedanaesthesia in all species of domestic animal withoutany reports of harmful effects. Halothane is,however, broken down by ultraviolet light andsamples removed from an anaesthetic system foranalysis by an ultraviolet absorption meter shouldnot be returned to the breathing circuit, andindeed it is for this reason that the economicalultraviolet method of anaesthetic gas analysis is nolonger used.Sevoflurane when used in closed systems, producesa number of breakdown products of which‘Compound A’ (CF 3 =C(CF 3 )-O-CH 2 F) is nephrotoxicin rats. Although toxic values (in rats) usuallyneed to exceed 1000 ppm, under certain circumstanceslevels as low as 50 ppm may causemedullary tubular necrosis (Callan et al., 1994).The concentrations of Compound A which occurare greatest at higher temperatures, with dryabsorbents, with low flow or closed systems and,not surprisingly, with high concentrations of sevoflurane(Baum & Aitenhead, 1995). Levels in manand the dog using closed systems are usuallyabout 20 ppm, but in certain circumstamces reachover 50 ppm in individuals (Smith et al., 1996).Nevertheless, in man there is no evidence thatrenal failure has resulted from sevoflurane anaesthesia(Malan, 1995).The passage of some volatile anaesthetic agentsover very dry CO 2 absorbents results in accumulationof carbon monoxide (CO) within a closedanaesthetic system. Of the volatile agents in commonuse, desflurane produces the greatest amountof CO, and halothane probably the least (Fanget al., 1995). The problem can be avoided by turningoff the O 2 flow of ‘fail-safe’ machines whenthey are not in use to avoid the drying effect ofcontinuous gas flow through the system.BIOTRANSFORMATION OF ANAESTHETICGASES AND VAPOURS AND ORGANTOXICITYDamage to organs as a result of inhalation anaestheticagents may be due to direct toxic effects ofthe agent, to effects mediated by metabolites, or tohypoxic changes, usually from poor organ bloodflow. Except in sensitivity reactions the toxicity ofthe unchanged compound is normally directlyrelated to the concentration present and decreasingthe concentration present and/or the duration ofexposure to it will decrease toxicity. Metabolite formationis more complicated and may be fasterwhen the concentration of the parent compound islow. The mechanism of this concentration/timedependence is unknown but it seems that biotransformationreaches a maximum at relatively low

INHALATION ANAESTHETICS 135concentrations of anaesthetic and later as its concentrationin the liver increases the efficiency of theenzyme system decreases. The plateau in biotransformationrate could be because the amount ofenzyme available becomes the rate limiting factoror its activity is depressed either by inhibition dueto the anaesthetic substrate or the metabolites produced.The important implication for toxicitycaused by metabolism of anaesthetics is thatgreater quantities of metabolites may be producedby subanaesthetic concentrations than by exposureto an anaesthetizing concentration when each isadministered for the same number of MAC hours.Furthermore, increasing the duration of anaesthesiadoes not proportionally increase the quantity ofmetabolites produced in the body. Finally, while alarge reduction in the concentration of an administeredanaesthetic might reduce direct toxicity tobelow threshold for harm this might not be the casefor indirect toxicity due to metabolites.Toxic effects of anaesthetic drugs are most commonlyseen in the liver and kidneys. The mostcommonly cited example is that of halothane,which is extensively metabolized, catalysed byenzymes such as cytochrome P450. Breakdownproducts include trifluoroacetyl halides, whichcan link to liver proteins. In some cases antibodiesare formed against the halothane-induced antigen,resulting in immune mediated liver damage (theso-called ‘halothane hepatitis’). However, isofluraneand enflurane produce similar breakdownproducts to halothane, but to a lesser extent, sosimilar autoimmune mediated hepatitis may occur(Frink, 1995; Kenna & Jones, 1995), but moreuncommonly. The renal damage which wasreported following the prolonged use ofmethoxyflurane was thought to be due to theaction of free fluoride ions formed from hepaticmetabolism. The threshold for plasma fluoride tocause nephrotoxicity is approximately 50 mmol/l.However, levels close to this occur after prolongedenflurane or seveflurane anaesthesia, but appearto have only transient effects and serious renaldamage is rare (Kenna & Jones, 1955).DEPRESSION OF VITAL BODY FUNCTIONSIn experiments on isolated organs all anaestheticshave a depressant effect but in an intact animalthese depressant effects may be modified or evencontrolled by various mechanisms. With theexception of N 2 O, all the inhalation anaestheticsproduce a concentration dependent depression ofrespiration although there is some difference ofdegree between the agents currently used in theirtendency to produce this effect. In clinical practicethis is offset by surgical stimulation so that all thestandard agents can be used in spontaneouslybreathing animals without undue accumulation ofcarbon dioxide provided excessively deep levels ofcentral nervous depression are avoided.On the cardiovascular system all the inhalationalagents have a directly depressant action and thedifferences in their overall effects can be attributedto their action on baroreceptor activity and on theactivity of the sympathoadrenal system as reflectedin plasma adrenaline and noradrenaline.The direct effects on the cardiovascular system areopposed by sympathetic activity resulting fromsurgical stimulation and the changes in cardiovascularfunction seen will depend on the balancebetween inhibitory and excitatory influences.INTERACTION WITH OTHER DRUGSAll neuromuscular blocking drugs are potentiatedby inhalational anaesthetics in a dose-dependentmanner and since muscle relaxation quite adequatefor most operations can be produced byinhalation agents alone it is reasonable to assumethat at least part of this potentiation is due to thecentral nervous depression produced by theanaesthetic agent. In addition, it has been shownthat inhalational agents decrease the sensitivity ofthe postjunctional membrane of the neuromuscularjunction and possibly act at a more distal sitesuch as the muscle membrane itself. The differentanaesthetic agents differ in the extent they potentiaterelaxants. For example, enflurane and isofluraneare considerably more potent in potentiatingd-tubocurarine in man than are halothane or N 2 O(Ali & Savarese, 1976). The reason for this is quiteunknown but, clearly, it may be considered advantageousfor an inhalational agent to contribute toneuromuscular block since this component canbe removed by ventilation of the lungs, so increasingthe flexibility of control because there are thenat least two methods of reducing or abolishing

136 PRINCIPLES AND PROCEDURESthe block – use of an anticholinesterase and augmentedventilation.The sensitization of the myocardium to bothendogenous and exogenous adrenaline by theinhalational agents has been the subject of muchinvestigation and it can be concluded that whilestraight-chain hydrocarbons tend to sensitize theheart to catecholamines, the ethers, especially iffluorinated, do not have this effect. Indeed, fluorinatedethers such as enflurane and isoflurane, havethe desirable attribute of conferring good stabilityto adrenaline.ANALGESIAFor as yet unknown reasons subanaesthetic concentrationsof agents such as nitrous oxide producemarked analgesia, whereas others such ashalothane do not. It may be speculated that thiseffect depends on the release of endorphins(encephalins) but, except for N 2 O evidence for thisis lacking. If an agent having good analgesic propertieshas a high solubility (e.g methoxyflurane)then elimination of it will be slow and analgesiawill be present during recovery. Unfortunately,less desirable effects such as respiratory depressionand arterial hypotension are also prolongedso that it is usually better to rely on specific analgesicdrugs in the postoperative period rather thanthe retention of the anaesthetic agent.INDIVIDUAL INHALATIONANAESTHETICSNITROUS OXIDE (N 2 O)N 2 O is a colourless gas with a faint, rather pleasantsmell; it is not flammable or explosive but it willsupport combustion, even in the absence of freeO 2 . Compressed into cylinders (‘tanks’ in NorthAmerica) at 40 atmospheres pressure it liquifies sothat the amount in a cylinder can only be determinedby weighing since the pressure of thegaseous N 2 O above the liquid level remains constantas long as any liquid remains. Thus a pressuregauge screwed into the cylinder outlet willregister a constant pressure until all the N 2 O hasvaporized and after this the reading drops rapidlyas gas leaves the cylinder. Some type of ‘regulator’or pressure-reducing valve must be attached to thecylinder before the rate of flow of the gas can beaccurately adjusted or measured.It is not irritant to the respiratory mucosa andbecause short periods of inhalation do not causetoxicity it was given for prolonged periods inintensive care units. However, exposure to it forseveral days caused bone marrow depression inhumans due to interference with methionine synthasegiving rise to disturbances of folate metabolismand megablastosis (Armstrong & Spence,1993). N 2 O has little or no effect on the liver andkidneys and although it has a direct depressanteffect on the myocardium this is offset by its sympatheticstimulating properties.The results of several studies suggest that N 2 Omay increase pulmonary ventilation (Eckenhoff &Helrich, 1958; Hornbein et al., 1982; Hall, 1988).The tachypnoea produced by N 2 O may result fromdirect central stimulation similar to that postulatedfor potent inhalation agents but the impact ofN 2 O appears to be greater than that of otherinhalation anaesthetics. The greater increase in respiratoryrate and minute ventilation associatedwith its use is also found when it is combined withsome of the inhaled anaesthetics but not with opioidanalgesics. Respiratory rate and minute ventilationare greater at a given MAC level when N 2 Oand isoflurane are combined than when isofluraneis given alone (Dolan et al., 1974). This is also truefor halothane but not enflurane. Adding N 2 O to astable level of alfentanil narcosis appears to haveno effect (Andrews et al., 1982).As already discussed N 2 O tends to enter gasfilledspaces in the body at a greater rate thannitrogen can diffuse out. This is of considerableimportance in herbivores and in the presence of aclosed pneumothorax.During the induction of anaesthesia a large gradientexists between the tension of N 2 O in theinspired gas and the arterial blood so that in theearly moments of induction the blood takes uplarge volumes of gas. Its rapid removal from thealveoli by the blood elevates the tension ofany remaining (second) gas or vapour such as oxygen,or a volatile anaesthetic agent, and augmentsalveolar ventilation. Thus, during the first fewminutes of N 2 O administration anaesthetic uptake

INHALATION ANAESTHETICS 137is facilitated because the enhanced tension of thesecond gas ensures a steeper tension gradient forits passage into the blood. This is known as ‘thesecond gas effect’.The phenomenon known as ‘diffusion hypoxia’occurs immediately following anaesthesia whenthe gas is being rapidly eliminated from the lungs;N 2 O may form 10% or more of the volume ofexpired gas, and the outward diffusion of N 2 O intothe alveoli lowers the the partial pressure of O 2 inthe lungs (PaO 2 ). This effect appears to have littleclinical significance in healthy animals but anyhypoxia may be dangerous in elderly animals or inthose suffering from cardiovascular or pulmonarydisease and such animals should have an O 2enriched mixture to inhale for some 10 minutesafter the termination of N 2 O administration. Manyanaesthetists consider that even healthy animalsbenefit from 5–10 minutes of O 2 inhalation whenN 2 O is discontinued at the end of a lengthyprocedure. When the insoluble agent desflurane isused with N 2 O, it is imperative that O 2 is given forsome minutes after termination of the anaestheticadministration.Being only a very weak anaesthetic, with aMAC of over 100%, N 2 O cannot, on its own, beused to produce anaesthesia because it must begiven with sufficient O 2 (>25%) to prevent hypoxia.Its strong analgesic properties make it most usefulto provide additional analgesia for bothintravenous and inhalation anaesthetic agents, i.e.it is best regarded as an anaesthetic adjuvant.DIETHYL ETHERDiethyl ether, commonly known simply as ‘ether’,was one of the earliest inhalation anaestheticsintroduced into clinical practice but its use iscurrently declining rapidly. The chief reasonfor this is its inflammability and also its greatwater and blood solubility which, together withits irritant smell, make for a slow inductionand recovery. Nevertheless, ether has always hadthe justification of being a very safe anaestheticagent.It is a transparent, colourless liquid with avapour twice as heavy as air, which is highlyinflammable in air and explosive in O 2 rich atmospheres.Ether is decomposed by air, light and heat;the liquid is, therefore, stored in amber-colouredbottles kept in a cool dark place. Its heavy vapourtends to pool on the floor and unless ventilation isgood the possibility of fires is very great. Sparks ofstatic electricity from faulty connections in electricalswitches and apparatus can easily igniteether/air mixtures and ether/oxygen mixtures areexplosive. Fires have resulted from the vapourrolling into an adjoining room and being ignitedthere. Ether should not be administered in locationswhere equipment such as radiographic apparatusor diathermy is to be used.Ether is safe in the presence of adrenaline.Indeed, its administration is associated with sympathoadrenalstimulation which opposes its negativeinotropic effect and the concurrent use ofβ-adrenergic blocking drugs allows this effect tobecome dangerous. Normally, cardiac output iswell maintained even at deep levels of unconsciousness.During light levels of unconsciousness,ether does not depress respiration. Thespleen contracts while the intestines becomedilated and atonic. The blood sugar level risesdue to the mobilization of liver glycogen underthe influence of the increased secretion of adrenaline.Liver and kidney function is depressed butthese organs usually recover their normal functionwithin 24 hours. The inhalation of ether causesmetabolic acidosis and ketone bodies may appearin the urine. Although ether does undergo somemetabolism it contains no halogens so that itsintermediate metabolites are such relatively nontoxicsubstances as ethyl alcohol, acetic acid andacetaldehyde.Ether possesses many disadvantages in additionto its inflammability. Its inhalation provokesthe secretion of saliva and of mucus within therespiratory tract (although this problem can becounteracted by premedication with an anticholinergicagent). In man, postanaesthetic nauseaappears to be pronounced and it is a fact that animalsare reluctant to eat for several hours followingether anaesthesia, possibly indicating they tooexperience nausea.Ether has now been in continuous use for wellover 100 years and millions of operations musthave been performed on animals under etheranaesthesia. The number of deaths directlyattributable to ether, apart from accidents (e.g.

138 PRINCIPLES AND PROCEDURESexplosions and fires) and errors of technique, mustbe very small indeed or its use would have beendiscontinued long ago. It must still be considered asafe agent for the inexperienced anaesthetist to usebecause, in addition to being slow in action, it producesa graded series of signs useful in indicatingthe depth of central nervous depression.CHLOROFORMChloroform is a most powerful anaesthetic whichis no longer used. It has a toxic effect on the liverand kidneys, causing cloudy swelling and evenacute fatty change in the cells. When severe thesechanges give rise to delayed poisoning, the symptomsof which develop some 24–48 hours afteradministration. Delayed poisoning is characterizedby acute acidosis, severe vomiting (indogs and cats), acetonuria, albuminuria, mildpyrexia and icterus, and frequently terminatesfatally with severe hyperpyrexia. In addition,chloroform sensitizes the myocardium to theeffects of catecholamines and sudden death hasoccurred from ventricular fibrillation duringanaesthesia or recovery from chloroform.CYCLOPROPANECyclopropane is as inflammable as ether and mixtureswith both air and oxygen are explosive. It hassolubility characteristics which commend it as ananaesthetic agent for induction and recovery but itproduces marked respiratory depression. In the1950s it was extensively employed in veterinaryhospitals in the UK and was noted for causingvomiting in the recovery period in pigs and dogs.The explosion risk associated with its use is a veryreal one and it is no longer available.HALOTHANEHalothane was introduced into veterinary anaesthesiain 1956 (Hall, 1957) and was so greatly superiorto existing agents that it soon became usedthroughout the world. It is probable that halothanehas been subjected to more investigational studiesthan any other anaesthetic agent and in the veterinaryfield alone there is now an extremely largenumber of references to this agent.Vapour concentrations from 2 to 4% in theinspired air produce smooth and rapid inductionof anaesthesia in all species of domestic animal.Anaesthesia can then be maintained with inspiredconcentrations of 0.8 to 2%, the MAC beingabout 0.85% in all mammals. Recovery from shortdurationhalothane anaesthesia is also reasonablyrapid and free from excitement although unrelievedpain can give rise to restlessness duringrecovery. When no other agents are administeredmost animals are able to walk without ataxia in15 to 30 minutes, depending on the duration of anaesthesiaand the degree of obesity of the animal.Blood concentrations are around 14 mg/dl duringmaintenance of anaesthesia and fall rapidly duringrecovery so that levels of 4–6 mg/dl have beenrecorded 15 minutes after the discontinuation ofadministration.The mucosa of the respiratory tract is not irritatedand and it is for this reason that halothane has(until the advent of sevoflurane), remained theagent of choice in man for mask induction ofanaesthesia. Halothane has been shown to producebronchodilatation with an increase in expiratoryreserve volume in ponies (Watney et al., 1987).The PaCO 2 is directly related to the alveolar concentrationof halothane when this is above 0.7%(Merkel & Eger, 1963).Halothane causes a dose-dependent depressionof cardiac output and arterial blood pressure duemainly to a negative inotropic effect although itdoes cause some block of transmission at sympatheticganglia. Evidence for the mode of action ofhalothane on the peripheral vasculature is stillboth controversial and more than a little confusing.In dogs Perry et al. (1974) showed that halothanedecreases plasma catecholamine levels andthis may explain the reduction of arterial pressureand decreased myocardial contractility and cardiacoutput.Dose-dependent respiratory depression occurs,both the depth and rate being decreased so that theminute volume of respiration is greatly reducedleading to a progressive rise in PaCO 2 until equilibriumbetween production and elimination ofthis gas is reached. In small dogs and in catstachypnoea has been related to a central action ofthe anaesthetic (Mazzarelli et al., 1979; Berkenboschet al., 1982). Except in horses, respiratory

INHALATION ANAESTHETICS 139failure from overdose precedes cardiac failure by aconsiderable margin. Adaptation of both cardiovascularand respiratory function occurs with time(Steffey et al., 1987) After about four hours cardiacoutput in horses increases by about 40% from thatat 30 minutes and the values for PaCO 2 and theratio of inspired to expired gas flow become significantlyhigher than those at 30 minutes of anaesthesia.Bradycardia is common during halothaneanaesthesia due apparently to activity in the vagusnerves. Usually a perfectly normal electrocardiogrampersists throughout anaesthesia althoughventricular extrasystoles and bigeminal rhythmhave been reported as occurring in dogs; these canlargely be prevented by premedication with acepromazine(Wiersig et al., 1974). In cats A-V dissociationwith interference and extrasystoles mayoccur (Muir et al., 1959). Arrhythmias are usuallyassociated with CO 2 accumulation from respiratorydepression, hypoxia, catecholamine releaseand overdosage. Changes in heart rate and rhythmshould not be treated with atropine as a routinesince the abolition of vagal tone may accentuatetheir severity and even induce ventricular fibrillation.Catecholamine-induced tachyarrhythmiasmay be treated with propranolol or by switchingto another inhalation agent.Halothane has minimal neuromuscular blockingeffect and the muscle relaxation seen duringhalothane anaesthesia (which is only moderate atdeep levels of central nervous depression) does,however, potentiate the effects of non-depolarizingmuscle relaxants and antagonize those ofdepolarizing agents (Graham, 1958). Shivering isoften seen in all species of domestic animals duringrecovery but the reason for it is not completelyunderstood. It does not seem to be related to wholebody or environmental temperature and its onlyimportance is that it may be harmful by increasingoxygen demands in animals suffering from respiratoryand/or cardiovascular diseases which limitoxygen uptake when they are breathing air.Because of its lack of analgesic propertieshalothane anaesthesia is more affected by premedicationwith analgesic drugs than is the case formany other agents. This also applies to supplementationduring anaesthesia with analgesics,whether these be of the opioid type or analgesicmixtures of N 2 O and O 2 . Postoperative analgesiaduring recovery is not a feature of unsupplementedhalothane anaesthesia.Minimal pathological changes have been foundin the liver and kidneys of dogs, horses and sheepanaesthetized for long periods with halothane(Stephen et al., 1958; Wolff et al., 1967). Susceptibilityto hepatic damage varies from speciesto species. For example, rat liver microsomes,which contain the cytochrome P450, will bindto reductive metabolites of halothane and ifthese microsomal enzymes are pre-inducedhepatoxicity results. Mice have the same isoenzymeP450 as rats but even when this is induced,hepatotoxicity cannot be provoked by halothane(Gorsky & Cascorbi, 1979). The guinea pig doesnot metabolize halothane well under reductiveconditions, yet develops hepatoxicity (Lunamet al., 1985).The question of hepatotoxicity in man has beenmuch discussed but its actual incidence seemssmall because the estimated incidence of fatal fulminanthepatic failure is less than 1:35 000(National Halothane Study, Washington DC, 1969)and is associated with repeated exposure to thedrug, often at short intervals (Elliott & Strunin,1993). A second, more common syndrome, characterizedby moderately increased concentrations ofliver transaminases and sometimes transient jaundice,carries a low morbidity. These conditions,however, only relate to people given halothaneanaesthetics and the veterinary anaesthetist ismore concerned by the risk of adverse effectsfrom exposure of anaesthetic personnel to the lowconcentrations of halothane in operating rooms.After a detailed and extensive review, Armstrongand Spence (1993) concluded that evidence for asevere problem with pollution from anaestheticwaste gases, including halothane, is small butnevertheless they may cause adverse effects inpregnant women and have an effect on theimmune system (although this is probably of noclinical relevance).Halothane and ether form an azeotropic mixture(31.7% diethyl ether and 68.3% halothane,v/v) with a boiling point of 51.5 °C. This mixturehas been employed in veterinary anaesthesia(Hime, 1963) but it is an illogical one and is nolonger used.

140 PRINCIPLES AND PROCEDURESMETHOXYFLURANEMethoxyflurane is a clear, colourless liquid whichboils at 104.65 °C. at 760 mmHg (101 kPa) pressureand freezes at –35 °C. Although the boiling point isslightly higher than that of water it volatilizesmore readily as a result of low latent heat of vaporization(49 cal/g). It is non-explosive and noninflammablein air or oxygen and conditionsencountered in anaesthesia.It is chemically stable and is not decomposed byair, light, moisture or alkali such as soda lime. Itmay, however, slowly form a brownish discolorationdue to the antioxidant used in its formulation.Chenworth et al. (1962) have shown that theurine contains only minute traces of methoxyflurane,but polyuric renal dysfunction (high outputrenal failure) has been reported in people andlaboratory animals. It follows the prolongedadministration of high concentrations and is saidto be due to the release of free fluoride by metabolismin the body: this resulted in the withdrawal ofmethoxyflurane from medical practice. High outputrenal failure, except when flunixin was givenconcurrently, has not been reported in veterinaryanaesthesia where methoxyflurane was usedextensively for small animals. The agent has nowbeen completely withdrawn from clinical use bythe manufacturers, although it can still be obtainedfrom them for research purposes and is apparentlystill available in Australia.ISOFLURANEIsoflurane is similar to enflurane in general, physicaland chemical properties. A great deal of experimentalwork has been carried out in evaluatingisoflurane and comprehensive reviews of its pharmacologicalproperties are those of Eger (1981),Wade & Stevens (1981) and Forrest (1983). Isofluranedoes not decompose in the presence of moistsoda lime but has been reported to interact withdry carbon dioxide absorbents to form carbonmonoxide (Rhône Mérieux Ltd, Data Sheet).It may be administered with oxygen or nitrousoxide/oxygen mixtures and because it is a potentanaesthetic an accurately calibrated vaporizershould be used. Isoflurane has a pungent odourbut animals breathe it without breath holding orcoughing. Clinical signs of anaesthesia resemblethose seen with halothane.Like most inhalation agents it undergoes somebiotransformation (approximately 1%), the mainmetabolites being trifluroacetic acid and inorganicfluoride, but the possibility of fluoride nephrotoxicityis very remote. Respiratory and cardiovasculardepression are dose-dependent. Respiratorydepression in the unstimulated subject is greaterthan with halothane but surgical stimulationcounteracts this and tends to equalize respiratoryrates under anaesthesia with the two agents.Arterial blood pressure is as depressed as it isunder halothane anaesthesia. However, heartrate is increased and cardiac output and strokevolume are reduced less than they are withhalothane; a greater fall in peripheral resistancemust be responsible for the similarity of theblood pressure response, for at clinical concentrationshalothane has little effect on totalperipheral resistance. There is evidence that at1.5 and 2.0 × MAC isoflurane lowers peripheralresistance and maintains or increases blood flow toorgans and muscle. Arrhythmias have not beenreported and because it is an ether irregularitiesfollowing the injection of catecholamines are lesslikely to occur than under halothane anaesthesia.In horses a limited number of tests have shownminimal or no toxicity (Davidcova et al., 1988)and recovery is usually quiet although problemswith the quality of recovery have been reported,particulary after the use of ketamine as an inductionagent. The quick elimination of isofluraneallows mares to nurse shortly after completion ofsurgery.The high volatility, coupled with low blood solubility,provide for relatively rapid induction andrecovery and easy control of the depth of anaesthesia.Its low solubility in fatty tissues avoids accumulationin obese subjects. Isoflurane increasessplanchnic blood flow and thus enhances hepaticoxygenation. Renal blood flow is well maintainedduring isoflurane anaesthesia and because there isvery little production of fluoride ions, coupled withless than 1% elimination via the kidneys, it can generallybe administered quite safely to animals withrenal dysfunction. Isoflurane should not be used inanimals with a known susceptibility to malignanthyperthermia. Fully comprehensive data concern-

INHALATION ANAESTHETICS 141TABLE 6.2 Inspired concentrations for theinduction and maintenance of anaesthesia withisoflurane for different species of animal.Theprecise concentration depends on the otherdrugs administered and the type of anaestheticdelivery system.The concentrations shownhere refer to situations where the induction ofanaesthesia has been with isoflurane alone andcould represent gross overdoses whenanaesthesia is induced with other drugs (dataSPECIESing its use in pregnant, breeding or lactating domesticanimals are not yet available, althoughFunkquist et al. (1993) have reported its use forcaesarian section in bitches. The use of isofluranein reptiles has been reported by Hochleithner(1995).Despite the popularity isoflurane has gained,especially in North America, it is doubtful whetherit will replace halothane in veterinary anaesthesiaexcept possibly in certain indications such as inobese animals or those suffering from cardiac disease.The much publicized rapid recovery has notbeen substantiated in dogs (Zbinden et al., 1988).Moreover, after propofol induced anaesthesiamaintained with isoflurane/N 2 O/O 2 (Peshin &Hall, 1996) significant differences in recoverytimes from halothane, enflurane and isofluranewere not observed (Table 6.3).ENFLURANEMAC (%) Induction (%) MaintenanceHorse 1.31 3.0–5.0 (foals) 1.5–2.5Dog 1.28 Up to 5.0 1.5–2.5Cat 1.63 Up to 4.0 1.5–3.0Ornamentalbirds About 1.45 3.0–5.0 0.6–5.0Reptiles ? 2.0–4.0 1.0–3.0Mouse 1.34 2.0–3.0 0.25–2.0Rat 1.38–2.40 2.0–3.0 0.25–2.0Rabbits 2.05 2.0–3.0 0.25–2.0Enflurane was first synthesized in 1963 and wasreleased for general clinical use in people in NorthAmerica in 1972. Fears about possible epileptogenicproperties have not been realized althoughsome anaesthetists have reported muscle twitchingin enflurane anaesthetized dogs. Like halothaneit depresses cardiovascular function in aTABLE 6.3 Median recovery times toswallowing,response to voice,spontaneoushead lift and walking without ataxia in 12 dogsafter anaesthesia induced with propofol andmaintained for a median time of 18 minuteswith halothane,enflurane and isoflurane inN 2 O / O 2 .None of the dogs receivedpremedication or underwent surgicalprocedures (data from Peshin & Hall,1996)from Mallinckrodt Veterinary,1996) Agent Time to Time Time Time toswallowing response to head walking(min) to voice lift (min)(min) (min)Halothane 3 5 8 12.5Enflurane 2.2 4.5 8 12Isoflurane 4.5 8 10 12.5dose-dependent manner, and the effects of the twoagents are comparable. It has a negative inotropiceffect on the canine heart, which is accompaniedby a decrease in myocardial oxygen demand. Inequipotent concentrations enflurane causes slightlygreater impairment of left ventricular functionthan does halothane (Horan et al., 1977). Heart rateand rhythm are stable with enflurane and it onlymildly sensitizes the heart muscle to catecholamines.Thus, subcutaneous injection ofadrenaline by the surgeon is unlikely to cause seriouscardiac irregularities. Arterial hypotension isoften a conspicuous feature (Wolff et al., 1967;Steffey et al., 1975). Comparative studies of equipotentconcentrations of enflurane, isoflurane,sevoflurane and halothane in dogs showed thatenflurane produced the greatest falls in cardiacoutput and arterial blood pressure (Mutoh et al.,1997). Under light anaesthesia surgical stimulationproduces an immediate increase in arterial bloodpressure, possibly due to increased sympatheticactivity. All the commonly used neuromuscularblocking drugs are compatible with this agent butthe actions of the non-depolarizing relaxants maybe markedly enhanced so that smaller dosesbecome adequate.The degree of metabolic biotransformation isapproximately 2–8% (Elliot & Strunin, 1993). Theproduction of inorganic fluoride is probably notgreat enough to pose a threat to the health of normalkidneys so any potential hazard from renalfluoride toxicity is unlikely to occur but ‘enflurane

142 PRINCIPLES AND PROCEDUREShepatitis’ has been reported. The ability to producerapid changes in the depth of anaesthesia coupledwith apparent absence of adverse side effects suggestedthat this agent might be useful in veterinarypractice, particularly for horses and small animalsundergoing surgery on a day case basis. In horsesrecovery not covered by xylazine administration isunpleasant (Taylor & Hall, 1985) but in dogs enfluranehas been used very satisfactorily for radiotherapytreatment (Peshin & Hall, 1996).FFFCFFCHCCIHCOOFCFFCHHIsofluraneDesfluraneDESFLURANEDesflurane is a fluorinated methyl ethyl ether, differingfrom isoflurane only in the substitution offluorine for chlorine at the α-ethyl carbon atom(Fig.6.1). It is a clear, colourless and virtuallyodourless fluid, with a boiling point of 23.5 °Cand a saturated vapour pressure of 88.53 kPa(664 mmHg) at 20 °C. Substitution of fluorine forchlorine on the α-ethyl carbon atom confers a highdegree of chemical stability so that desflurane canbe stored at room temperature for up to one yearwithout the need for added preservatives. It is notdegraded by artificial light and is inflammable at aconcentration of 17%.Although decomposing when in contact withdry soda lime it is not significantly decomposed bywarm, moist soda lime, thus it can be used in theminimal flow systems so important in the currentawareness of the need for cost containment inveterinary anaesthesia. Desflurane has a very lowsolubility in blood (0.42; N 2 O is 0.46 – Eger (1987))and might, therefore, be expected to induce anaesthesiavery rapidly, as well as permitting rapidchanges in depth of anaesthesia when the inspiredconcentration is altered (Eger, 1992; Smiley 1992;White, 1992; Jones & Nay, 1994). Similarly, recoveryshould be rapid. Problems have arisen in manwhere the quality of induction of anaesthesia iscomplicated by breath holding, coughing, laryngealspasm and increased airway secretions fromirritation of the airways (White, 1992; Smiley, 1992;Whitton et al., 1993). No similar problems havebeen reported when desflurane has been used toinduce anaesthesia in the dog and cat and dogsrecovered within 3–9 minutes following 5–9 hoursof desflurane anaesthesia (Hammond et al., 1994;McMurphy & Hodgson, 1994).FFFIG.6.1 Formulae of isoflurane and desflurane.FThe minimum alveolar concentration (MAC) ofdesflurane varies between species and betweenindividuals within that species. For example, themeasured MAC of desflurane in human surgicalpatients has been reported as 7.25% in the age group18–30 years and 6% in those aged 31–65 years(Rampil et al., 1991), while in neonates it is about9.16% (Taylor & Lerman, 1991). In non-human primatesMAC varies between 5.7 and 10.3% (Eger,1992). After induction of anaesthesia with xylazineand ketamine, Clarke et al. (1996, 1996a) reportedthe MAC in ponies aged 1 or 2 years to be 7.0% (SD0.85) with a range of 5.8 to 8.3%.In an individual the MAC of an inhalationagent does not usually vary by more than 10%(Quasha et al., 1980) and sudden large increases ofMAC during the period of measurement as reportedby Eger et al. (1988) or Clarke et al. (1996), havenot been reported for other inhalation agents.Desflurane boils at close to room temperature,and a special vaporizer, such as the Tec 6 vaporizerproduced by Ohmeda, is essential. Any volume ofgas flowing through the vaporizing chamber of atraditional vaporizer will contain several volumesof desflurane because of the high volatility of theagent. The resulting volume expansion will produceuncontrollable efflux of gas from the chamber.Moreover, the low potency of desfluranenecessitates the vaporization of large quantities ofliquid during the course of an anaesthestic and inthe absence of any heat source this will causeexcessive cooling of the vaporizer. In the specialvaporizer desflurane is contained in a sump whichis electrically heated and thermostatically con-

INHALATION ANAESTHETICS 143trolled to maintain a constant temperature of 37 °C,while an electronically controlled pressure regulatingvalve ensures a precise, controllable outputfrom the vaporizer which is not affected by the rateof gas flow through the sump but is reduced by upto 2% by the concurrent use of N 2 O in the carriergas flow (Johnston et al., 1994).Desflurane undergoes minimal metabolism(0.2%) and therefore the potential for toxicity islow (Koblin, 1992). It does not prevent the developmentof malignant hyperthermia in susceptiblepigs (Wedal et al., 1993) and in experimentalcircumstances the effects of desflurane on vitalorgan function are similar to those of isoflurane(Merin et al., 1991; Hartman et al., 1992; Warltierand Pagel, 1992) in that it causes dose-relatedvasodilatation, moderate impairment of myocardialfunction and a similar degree of respiratorydepression. The heart is not sensitized to adrenaline-inducedarrhythmias. However, experimentallyWeiskoptf et al. reported ‘sympathetic storms’in man whereby an increase in inhaled concentrationwas followed by tachycardia and an increasein arterial blood pressure (Ebert & Muzi, 1993;Weiskopft et al., 1994). Such sympathetic stormshave not been reported in animals but the variationsin reported MAC may be due to a similaroccurrence.The major potential advantages of desfluranein comparison with isoflurane result from itslow solubilities in blood and fat. However, inmost veterinary species it is probable that theadvantages are minimal. The exception is in thehorse (p.298), where desflurane renders it exceptionallyeasy to maintain stable anaesthesiaand is possible to run in a totally closed system,making it very economical in use. Clarke et al.(1996) reported that in ponies recovery after desflurane,when coupled with low dose xylazine (0.2mg/kg i.v. given after extubation), proved to beextremely rapid, quiet and uneventful; withoutxylazine, animals tended to fall at their firstattempt to stand.The availability of desflurane for use in animalswill probably depend on its fate in the medicalanaesthetic market where it does not seem to beproving popular because of its irritant nature (preventingmask inductions of anaesthesia) and theoccurrence of sympathetic storms.SEVOFLURANESevoflurane is a fluorinated ether (Fig. 6.2) whichhas been licenced for medical use in Japan since1990 and is now approved for clinical use in medicalpractice in the USA, the UK and ContinentalEurope. Although the blood/gas partition coefficientof sevoflurane is quite low (0.62), dictatingrapidity of uptake and elimination, thetissue/blood partition coefficients are greater thanthose of isoflurane (Table 6.4)The data in Table 6.4 do not prevent sevofluranebeing a rapidly acting general anaestheticwith faster induction and emergence than isoflurane,but not as fast as desflurane. Both inductionand emergence phases are smoothalthough there have been reports of emergenceexcitement in man and unsedated recoveries inhorses may be violent (Clarke, 1999). The vapourpressure of sevoflurane is such that a conventionalvaporizer can be employed rather than the special,and expensive, vaporizer required fordesflurane.The respiratory and cardiovascular (Ebert et al.,1995) actions of sevoflurane are similar to those ofthe other halogenated agents. No seizure-likeactivity has been noted for sevoflurane. Sevofluranedepresses myocardial contractility anddecreases peripheral blood flow but it is non-irritantto the respiratory passages so that induction ofanaesthesia is not complicated by coughing orbreath-holding.Sevoflurane undergoes biotransformation tofree fluoride ions and hexafluoroisopropanolwhich is rapidly glucuronidated. Its potential forhepatotoxicity is low as its metabolic pathway isnot via trifluroacetic acid, but the release of freefluoride ions has given rise to some concern.Investigations into this issue demonstrate no evidenceof renal toxicity and extensive clinical experiencein man has brought to light no cases of renalfailure following its use.FFCFFIG.6.2 Chemical structure of sevoflurane.HCOHCHF

144 PRINCIPLES AND PROCEDURESTABLE 6.4 Physiochemical and partition datafor isoflurane and sevoflurane in humansubjects (part.coeff.= partition coefficient)Sevoflurane IsofluraneBoiling point (°C) 58.5 48.5Vapour pressure (20 °C) 157 236Blood/gas partit.coeff. 0.62 1.36Oil/Gas part.coeff. 47 98MAC in O 2 (%) 2.05 1.20Tissue/fat part.coeff. 47.5 44.9Tissue/brain part.coeff. 1.70 1.57Tissue/muscle part. coeff. 3.13 2.92Tissue/liver part.coeff. 1.85 1.75Another question which has been raised concernsthe stability of sevoflurane in the presence ofstrongly alkaline carbon dioxide absorbers sincethe molecule is more susceptible to spontaneousbase degradation than are other anaestheticmolecules, such as those of isoflurane and desflurane.Two of the decomposition compoundsgenerated in carbon dioxide absorbers duringmedical clinical use are known as compounds Aand B. In clinical practice the maximum concentrationof the degradation product, compound A,was far below the toxic concentration foundexperimentally.The MAC of sevoflurane in horses has beendetermined by Aida et al. ( 1994) as 2.31 and Aidaet al. (1966) have described its cardiovascular andpulmonary effects in these animals. Its use followingatropine/xylazine/guaifenesin/thiopentalinduction of anaesthesia in horses was recorded byHikasa et al. (1994a).In adult spontaneously breathing cattle itsuse following atropine/guaifenesin/thiopentalinduction of anaesthesia was reported by Hikasaet al. (1994b), while Yasuda et al. (1990) comparedits pharmacokinetics with those of desflurane,isoflurane and halothane in pigs. Hikasa et al. studiedthe effects of these same agents in spontaneouslybreathing cats and compared theirventricular arrhythmogenic activities (Hikasaet al., 1996). Sevoflurane has also been used indogs (Mutoh et al., 1995, 1995a) and cats (Hikasaet al., 1994c). Its cardipulmonary effects were comparedwith those of halothane, enflurane andisoflurane in healthy Beagles by Mutoh et al.(1997).OCCUPATIONAL EXPOSURE TOINHALATION ANAESTHETIC AGENTSPersonnel are often exposed to trace concentrationsof inhalation anaesthetics in the atmosphere.Contamination of ambient air occurs during thefilling of vaporizers, via known or unsuspectedleaks in breathing systems, and accidental spillageof liquid agent. Personnel inhale and apparentlyretain these agents in their bodies for some hoursor even days and slow elimination of anaestheticssuch as halothane allows accumulation of retainedquantities from one day to the next and the persistentlow concentration of the agent may encouragethe formation of toxic metabolites.The Control of Substance Hazardous to HumanHealth (COSHH) regulations in the UK requireemployers to evaluate and control the risks tohealth for all their employees from exposure to hazardoussubstances at work. Occupational ExposureStandards (OES) on an eight hour timeweighted average (TWA) have been set by theHealth and Safety Commision and are shown inTable 6.5.The critical health effect was considered to betoxicity to reproduction but reproductive effectshave not been proven following occupationalexposures. In the USA levels of exposure whichshould not be exceeded are, for example, by governmentrecommendation 2.0 ppm for volatileagents and 25 ppm for N 2 O.There seems to be no good evidence on whichto base any recommendations such as those abovebut there is now a legal obligation in the UK foremployers to meet these conditions. Anaesthetiststhroughout the UK were united in opposing(unsuccessfully) the imposition of COSHH regulationsto anaesthetic practice. Monitoring of levelsof these supposedly hazardous substances in theTABLE 6.5 Occupational exposure standards(Health and Safety Commission of the UK).The standard for isoflurane is five times that forhalothaneHalothaneIsofluraneNitrous Oxide10 ppm50 ppm100 ppm

INHALATION ANAESTHETICS 145environment will, of course, entail expense for thepurchase of suitable equipment. It must also benoted that work using better controlled groupsand improved methods of data collection indicatethat pollution of theatre atmosphere with anaestheticgases is not as great a hazard as was thoughtsome 20 years ago (Armstrong & Spence, 1993).However, even now there is still sufficient doubtabout the safety of trace concentrations of anaestheticgases for further research to be needed.REFERENCESAida, H., Mizuno, Y., Hobo, S., Yoshida, K. and Fujinaga,T. (1994) Determination of the minimum alveolarconcentration (MAC) and physical response tosevoflurane inhalation in horses. Journal of VeterinaryMedical Science 56: 1161–1165.Aida, H., Mizuno, Y., Hobo, S., Yoshida, K. and Fujinaga,T. (1996) Cardiovascular and pulmonary effects ofsevoflurane in horses. Veterinary Surgery 25: 164–170.Andrews, C.J.H., Sinclair, M., Dye, A., Dye, J., Harvey, J.and Prys-Roberts, C. 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INHALATION ANAESTHETICS 147adult and geriatric patients. Anesthesia and Analgesia74 (Suppl 4): 38–46; discussion S44–S46.Smith. I., Nathanson, M. and White, P.F. (1996)Sevoflurane – a long awaited volatile anaesthetic.British Journal of Anaesthesia 76: 435–445.Steffey, E.P., Gillespie, J.R., Berry, J.D., Eger, E.I.II andRhode, E.A. (1975) Circulatory effects of halothaneand halothane-nitrous oxide anaesthesia in the dog:spontaneous ventilation. American Journal of VeterinaryResearch 36(2): 197–200.Steffey, E.P. Kelly, A.B. and Woliner, M.J. (1987) Timerelated responses of spontaneously breathing,laterally recumbent horses to prolonged anesthesiawith halothane. American Journal of Veterinary Research48(6): 952–957.Stephen, C.R., Margolisd, G., Fabian, L.W. andBourgeois- Garvardin, M. (1958) Laboratoryobservations with fluothane. Anesthesiology19: 770–781.Steward, A. et al. (1900) British Journal of Anaesthesia45: 282.Taylor, P.M. and Hall, L.W. (1985) Clinical anaesthesia inthe horse: comparison of enflurane and halothane.Equine Veterinary Journal 17: 51–57.Taylor, R.H. and Lerman, J. (1991) Minimum alveolarconcentration of desflurane and hemodynamicresponses in neonates, infants and children.Anesthesiology 75: 975–979.Wade, J.G. and Stevens, W.C. (1981) Isoflurane: ananesthetic for the eighties? Anesthesia and Analgesia60: 666–682.Warltier, D.C. and Pagel, P.S. (1992) Cardiovascular andrespiratory actions of desflurane: is desfluranediferent from isoflurane? Anesthesia and Analgesia75 (Suppl 4): S17–29; discussion S29–S31.Watney, G.C.G., Jordan, C. and Hall, L.W. (1987) Effect ofhalothane, enflurane and isoflurane on bronchomotortone in anaesthetized ponies. British Journal ofAnaesthesia 59(8): 1022–1026.Wedal, D.J., Gammel, S.A., Milde, J.H. and Iaizzo, P.A.(1993) Delayed onset of malignant hyperthermiainduced by isoflurane and desflurane compared withhalothane in susceptible swine. Anesthesiology78: 1138–1144.Weiskopf, R.B., Moore, M.A., Eger, E.I. II, Noorani, M.,McKay, L., Chortkoff, B., Hart, P.S. and Damask, M.(1994) Rapid increase in desflurane concentration isassociated with greater transient cardiovascularstimulation than with rapid increase in isofluraneconcentration in humans. Anesthesiology80(5): 1035–1045.White, P.F. (1992) Studies of desflurane for outpatientanesthesia. Anesthesia and Analgesia 74 (Suppl 4):S47–S53; discussion S53–S54.Whitton, C.W., Elmore, J.C. and Latson, T.W. (1993)Desflurane; a review. Progress in Anesthesiology78: 46–58.Wiersig, D.O., Davis, R.H. and Szabiniewicvz, M. (1974)Prevention of induced ventricular fibrillation in dogsanesthetized with ultra-short acting barbiturates andhalothane. Journal of the American Veterinary MedicalAssociation 165(4): 341–345.Wolff, W.A., Lumb, W.V. and Ramsaya, K. (1967) Effectsof halothane and chloroform anesthesia on the equineliver. American Journal of Veterinary Research 28(126):1363–1372.Yasuda, N., Targ, A.G., Eger, E.I.II, Johnson, B.H. andWeiskopf, R.B. (1990) Pharmacokinetics of desflurane,sevoflurane, isoflurane and halothane in pigs.Anesthesia and Analgesia 71(4): 340–348.

Relaxation of the skeletal7musclesINTRODUCTIONTo relax skeletal muscles it is necessary to abolishvoluntary muscle contractions and modify theslight tension which is the normal state (the ‘tone’or ‘tonus’ of the muscle). Tone is maintained bymany complex mechanisms but, briefly, it can besaid that all result in the slow asynchronous dischargeof impulses from cells in the ventral hornregion of the spinal cord. This discharge gives riseto impulses in the α motor neurones which causethe muscle fibres to contract. Activity of these ventralhorn cells is controlled by impulses from thehigher centres (cerebrum, cerebellum, or medullaoblongata) exciting the α motor neurone direct, orby impulses through the small motor nerve fibresystem (the γ efferents) which activate them indirectlyvia the stretch reflex arc. Movements controlledby the γ fibre system are essentially directedtowards governing the length of the muscle.Voluntary movement, on the other hand, involvingdirect activity in the γ fibres, results in muscletension of a given magnitude.The relevance to anaesthesia lies in the fact thatthe small motor nerve fibre system is, like themotor fibres to the skeletal muscles themselves, acholinergic one. Any drug which can affect theneuromuscular junction may, therefore, also interferewith the effect of the γ-fibres on the musclespindles. A paralysis of the γ fibre/muscle spindlejunction will have, as a major consequence, areduction in the afferent inflow from the musclespindles and the mere reduction of such a flow tothe brainstem may have subtle effects. For example,there is a possibility that a drug which paralysesthe γ fibres and so reduces muscle spindleproprioceptive inflow to the higher centres actuallycontributes to a sleep-like state.METHODS OF ABOLISHING MUSCLE TONEAND ABILITY TO CONTRACTDuring anaesthesia abolition of muscle tone andability to contract can be brought about in threeways:1. By the use of anaesthetic agents which actcentrally.The anaesthetic agents cause decreased activityof ventral horn cells in the spinal cord and, thus,muscle relaxation. A profound degree of musclerelaxation can be obtained when a potent drug isadministered in doses which produce a deepgeneralized depression of the whole centralnervous system. However, the consequences arewidespread for these agents produce dosedependentdepression of the cardiovascular andrespiratory systems. Also, deep depression andimmobility in the recovery period can predisposeto complications such as pneumonia in horses andaspiration of regurgitated ingesta in ruminants orof stomach acid in other animals.Other centrally acting drugs, such asguaiphenesin, which produce muscle relaxation149

150 PRINCIPLES AND PROCEDURESby selectively depressing the transmission ofimpulses at the internuncial neurones of the spinalcord, brain stem and subcortical regions ofthe brain, may be more acceptable but therelaxation produced by them is seldom profound.Muscle relaxation can also be produced by thebenzodiazepines and α 2 adrenoceptor agonists butthis is weak and no substitute for the completerelaxation produced by neuromuscular blockingagents.2. Utilizing drugs which have a peripheral action.Local analgesics injected directly into a musclemass, or around nerve fibres or nerve endings,block the transmission of impulses and musclefibres are effectively isolated from nervousinfluences. This is strikingly demonstrated byparavertebral nerve block in cattle. At the sametime this method also has its disadvantages. Thetemperament of some animals renders themunsuitable subjects for the use of local analgesicsalone, especially when limb muscles are involved,and even in docile animals immobility of thewhole body can only be assured when localanalgesia is combined with general anaesthesia orvery deep sedation. The injection of localanalgesics is a time-consuming procedure andeven after simple techniques there is a delay beforethe full degree of relaxation is obtained. Inaddition, techniques such as neuraxial blocks cancause loss of control of much of the circulatorysystem as a result of paralysis of sympatheticnerves.In spite of the disadvantages it is probable thatcombinations of local analgesia and generalanaesthesia are used much less than they shouldbe in veterinary anaesthesia. Peripheral nerveblocks such as brachial plexus block, or epiduralblocks with low dose bupivacaine and opioids, arethe only reliable methods of preventing wind-upin the dorsal horn cells of the spinal cord and canthus make a marked contribution to postoperativepain control.3. Using specific neuromuscular blocking agents.Modern neuromuscular blocking agents havelittle or no significant action in the body other thanat the neuromuscular junction, and by their use itis possible to produce quickly, and with certainty,any degree of muscle relaxation withoutinfluencing the excitability and functioning of thecentral nervous and cardiovascular systems. Theyare commonly called ‘muscle relaxants’ or simply‘relaxants’.In order that their mode of action be understoodit is essential that the phenomena which occur atthe neuromuscular junction upon the arrival of animpulse in the motor nerve should be appreciated.The following brief review of neuromusculartransmission is concerned with those aspects thatare of importance in anaesthesia. For a detailedstudy of these phenomena reference should bemade to the standard texts of physiology.THEORY OF NEUROMUSCULARTRANSMISSIONThe neuromuscular junction is the most accessibleof the synapses in the body to study and over thelast 100 years very much has been revealed aboutit. Even so, there are many processes involved insynaptic transmission which still await explanation.It is now well established that acetylcholine issynthesized and stored in the motor nerve in vesicles,each of which contains one packet or ‘quantum’of acetylcholine. This is the transmittersubstance released as a result of a propagatedimpulse in the nerve fibre. After release, the acetylcholinediffuses across the synaptic gap (cleft) andinteracts with nicotinic acetylcholine receptorsembedded in the postjunctional membrane directlyopposite the sites of its release. This interactioncauses the receptor–ion channel complex toundergo a conformational change from a closed toan open state. The channnel is relatively nonspecificand in the open state it can conduct sodiumand potassium ions, together with other lessimportant cations, down their respective chemicaland electrical gradients resulting in a localized fallin membrane potential measured by physiologistsas the ‘end-plate potential’. The end-plate potentialcauses local circuit currents which lower themembrane potential in the electrically excitableadjacent muscle membrane and, if this lowering isof great enough amplitude, sodium channels opento initiate the muscle action potential which resultsin muscle contraction.Release of acetylcholine from the nerve terminaloccurs in discrete quanta and it is now believed

RELAXATION OF SKELETAL MUSCLES 151that transmitter release is an exocytotic processwhereby each quantum of acetylcholine releasedrepresents the exocytotic liberation of the contentsof a single synaptic vesicle found in the terminalregion of the nerve. Acetylcholine is synthesized inthe nerve cytoplasm by choline acetyl-O-transferaseand must be pumped into these vesiclesagainst its concentration gradient, but the mechanismby which this occurs is poorly understood.There must also be mechanisms which link the initiationof exocytosis and promote the fusion of thesynaptic vesicle membrane with the nerve terminalmembrane together with the formation of a‘pore’ linking the inside of the vesicle to the extracellularspace of the synaptic cleft. There is stillmuch controversy and uncertainty with respect tovesicular exocytotic processes.The release of acetylcholine can only occur atactive or ‘critical’ zones, meaning that there is alimited compartment of acetylcholine which canbe regarded as available for release. In simpleterms, ‘mobilization’ must occur, bringing reservesupplies of either acetylcholine itself or acetylcholine-containingvesicles into the available compartmentas depletion occurs from vesicularexocytosis. One proposal which has gainedground is that prejunctional nicotinic acetylcholinereceptors exist on nerve terminals allowinga positive feedback control mechanism suchthat acetylcholine can enhance its own release. Theimportance of effective mobilization becomes criticalat high rates of nerve stimulation when theacetylcholine output of the nerve terminal is greatest.The phenomenon known as ‘tetanic fade’, i.e.the inability of the muscle to maintain a constanttension in reponse to high frequency stimulationof its motor nerve, is used by some anaesthetists tomonitor the degree of neuromuscular block (Klide,1973). A rate of stimulation of 50Hz is consideredto be the maximum physiological rate as theevoked muscle tension is similar to that developedduring maximum voluntary effort.All nicotinic receptors so far isolated and characterized,function as cation channels, the activationof which causes a change in postjunctional membranepotential. Thus they behave in a similar mannerto receptors for other known chemicaltransmitters and belong to a family of closely relatedreceptors (5-HT 3 receptor, GABA A receptor,αβζIon channelαεExtracellular fluidIntracellular fluidLipid bilayercell membraneFIG.7.1 Diagram of the nicotinic receptor at theneuromuscular junction.There are thought to be fivesubunits,two of which,the α receptors,are similar.Theother subunits are called β,δ and ε. Another type ofnicotinic receptor has a γ subunit instead of ε,the so-calledextrajunctional or foetal receptor,because it occurs inrelatively low numbers outside the neuromuscularjunction in skeletal muscle.The five units are arranged as acylinder around a central funnel-shaped pore.glycine receptor and kainate-type glutamate receptor).The common element in this receptor family isthat the receptors consist of five glycosylated proteinsubunits of varying molecular type. In matureskeletal muscle these have been designated α, β, γ, δand ε (Fig. 7.1) having changed from embryonictypes during the neonatal period when the size andnumber of end plates and the number of receptorsincreases. Each of the subunits traverses the musclemembrane at the end plate region and they arearranged to form the walls of an aqueous pore representingthe ion channel through which mainlysodium and potassium ions flow to produce thesingle channel current measurable by the physiologists’patch-clamping technique.Neurotransmitter acetylcholine must bind tosites on two α subunits for the ion channel to openand produce the single channel current. Competitiveneuromuscular blocking agents bind onthese sites so that acetylcholine has a reduced

152 PRINCIPLES AND PROCEDURESchance of binding and opening the channel. It isknown that tubocurarine has different bindingaffinities for α subunits and it is possible that differentialbinding of other chemical classes of neuromuscularblocking agents may explain some ofthe interactions that can be observed clinicallywith such agents (Pedersen & Cohen, 1990).General anaesthetics, local analgesics and antibioticsare all potential causes of end plate ionchannel block. The most widely documented formof channel block is the ‘open channel block’(Lambert et al., 1983). After the channel is openedby acetylcholine this type of block is produced bydrugs which themselves have no affinity for thebinding sites on the α subunits but which, once thechannel is open, enter it and bind to amino acids inthe transmembrane domains. The result is that theactive or open form of the receptor becomesblocked in a non-competitive way and increasingthe agonist concentration (acetylcholine) leads tomore open channels and hence more opportunityfor the blocking compound to act. This type ofblock is, consequently, not reversible by anticholinesteraseagents such as neostigmine.Calcium is recognized as an essential intermediarylinking depolarization of the presynapticterminals to transmitter release. Release of acetylcholineis triggered by an increase in the concentrationof intracellular calcium ions (Ca ++ ).Depolarization opens channels in the membranethat allow calcium to pass into the cell, possiblythrough the cyclic adenosine monophosphate(cAMP) mechanism. Thus, it is generally believedthat depolarization activates membrane-boundadenyl cyclase which converts ATP to cAMP andthat the latter acts on a protein kinase which causesopening of the Ca ++ channel. Calcium itself doesnot cause transmitter mobilization and release – anessential intermediary is calmodulin, a Ca ++ bindingprotein which regulates its action. Binding offour Ca ++ to calmodulin changes its shape andactivates it. Activated calmodulin combines withan inactive receptor protein, activating it by changingits shape, and this activated form is known tobe associated with the aggregation of acetylcholinevesicles and their subsequent interaction with thepresynaptic membrane. It seems probable thatrelease of transmitter (exocytosis) is dependent oncalcium ions and calmodulin.Drugs may interfere with this complex Ca ++mechanism in many ways. For example, Ca ++antagonists such as verapamil may act by inhibitingcalmodulin combination. One molecule of thisdrug may be sufficient to block the uptake of severalthousand Ca ++ . There is evidence that thechange in quantal release of acetylcholine is proportionalto the fourth power of the change inCa ++ concentration. In dogs, a dose of 1mg/kg ofverapamil has been shown to produce a significantinteraction with the non-depolarizing agent, pancuronium,which persists long beyond the periodof the calcium antagonist’s cardiac effects (Jones,1984). Volatile anaesthetics may be considered tobe non-specific calcium antagonists and so potentiateneuromuscular blockade (Pollard & Millar,1973).In recent years there has been an increasingawareness that in addition to nicotinic cholinergicreceptors at the end plate there are prejunctionalreceptors which have an influence on normal neuromusculartransmission. It is thought that thereare at least two populations of presynaptic cholinergicreceptors, each subserving different physiologicalfunctions. One group is the presynapticnicotinic receptor which acts as a positive feedbackand responds to low concentrations of acetylcholineby facilitating its release at the end plate.This is believed to be mediated at least partly by itsaction on synapsin I causing an increase in theimmediately available store of the transmitter. Thesecond group are presynaptic muscarinic receptorswhich respond to a high concentration ofacetylcholine and act in a negative feedback mechanism.Stimulation of these receptors causesreduced release of transmitter in response to motornerve activity. There are also adrenoreceptors onmotor nerve endings which may modulatesynaptic function, and noradrenaline is known toincrease transmitter output in skeletal muscle.The catecholamine effect on the motor nerve endingsis thought to be an α effect in the presynapticregion contributing to an anticurare action; it contrastswith the β effect on the postsynaptic membranewhich leads to hyperpolarization and adeepening of non-depolarising neuromuscularblock.A remarkable property known as ‘desensitization’is displayed by the acetylcholine receptor of

RELAXATION OF SKELETAL MUSCLES 153striated muscle and its associated systems. Thisappears as the waning of a stimulant effect ordevelopment of repolarization (usually partial butunder some circumstances complete) despite thecontinued presence of acetylcholine or some otherdepolarizing substance at the end plate. The rate ofthis repolarization increases with the concentrationof the drug and is faster when the extracellularconcentration of Ca ++ is high. The extent of desensitizationappears to vary between individuals ofany one species. Acetylcholine has been shown tochange the affinity of the receptor for certainblocking agents in a way which may be connectedwith the desensitization process.NEUROMUSCULAR BLOCKConsideration of the mechanisms of neuromusculartransmission outlined above suggests manyways in which the process may be modified to producefailure or block of transmission.Non-depolarizing, antagonist, curare-like orcompetitive block results when the drug reducesthe degree of depolarization of the postsynapticmembrane caused by acetylcholine followingmotor nerve stimulation. When the reduction inthe degree of depolarization is such that a thresholddepolarization of the membrane adjacent tothe end plate is not achieved, a neuromuscularblock is present. As the effect is ‘all or none’ foreach motor end plate, what is seen in any particularmuscle during this type of block represents aspectrum of these thresholds. For complete suppressionof the motor response to occur even themost resistant synapses must be blocked.In normal neuromuscular transmission anexcess of acetylcholine is produced by motor nervestimulation. There also exist many more receptorsthan necessary for the production of a totalincrease in cation conductance required to triggeran action potential. This results in a substantial‘safety factor’ (Jones, 1984). It has been shown thatunder certain conditions in cat tibialis muscle fourto five times as much acetylcholine is released as isneeded for threshold action. Expressed in terms ofreceptors this means that 75–80% of the receptorsmust be occluded before the threshold is reached(Cookson & Paton, 1969).The existence of a safety factor has obviouspractical significance. It means, for example, thatthe action of the drug is far from terminated at thetime when transmission is apparently normal.There is likely to be considerable ‘subthresholdaction’ which is only detectable when a tetanicstimulus is applied to the motor nerve or whensome other drug is potentiated. It also explains theproperties of muscles partially blocked by competitivedrugs, such as the fall of tension during atetanus, the sensitivity of the depth of blockto anticholinesterases, catecholamines, previoustetanization, anaesthesia and a wide range ofdrugs.Depolarizing drugs will increase the variationof the safety factor. Slightly depolarized fibresbecome more excitable, i.e. their safety factorbecomes greater than normal conversely, deeplydepolarized fibres become less excitable. If thedepolarization is sufficient, the propagationthreshold may rise above the maximum depolarizationwhich can be achieved by acetylcholineand the safety factor becomes zero. It is likely thatthis underlies the general insensitivity of partialdepolarization block.Drugs which produce depolarization and thenprevent the passage of excitation from motornerves have been termed ‘depolarizing agents’and the analysis of their actions brought to light avariety of stimulant effects analogous to those ofacetylcholine itself, and attributable to end platedepolarization. In themselves, however, theseeffects do not explain how synaptic block is produced,nor why the overt signs of stimulation(such as fasciculations and limb movements) arequite transient although the depolarization persists.During the block produced by a depolarizingagent there is a decrease of electrical excitability ofthe postsynaptic membrane as a result of the persistingdepolarization (Burns & Paton, 1951).Depolarizing block may be followed by analteration of the threshold of the end plate regionto depolarization by acetylcholine. This ‘raisedthreshold block’ was originally described as ‘dualblock’ but now the commonly used term is ‘phaseII block’, indicating that it follows ‘phase I’ whichis the depolarizing activity of the drug. Phase IIblock following prolonged suxamethonium depolarizationmay be due to ‘channel block’, the

154 PRINCIPLES AND PROCEDURESmolecule of the drug being small enough to actuallypenetrate the open ion channels.In the past, neuromuscular block was classifiedas ‘depolarizing’ or ‘non-depolarizing’ (‘competitive’)solely on characteristics such as the responseto an anticholinesterase, behaviour during andafter the application of a tetanic stimulus, andinteraction with other drugs. This now seems adangerous outlook. Erosion of the safety factormakes it possible for a block to develop from quitea small rise in propagation threshold produced bya depolarizing drug without greatly increasing thevariation in safety factor; such a block would showmany of the characteristics of a competitive block.When it is realized that some neuromuscularblocking agents may be ‘partial agonists’ (i.e. possessinglimited ability themselves to depolarize aswell as to compete) and that drugs may act presynapticallyas well as postsynaptically, it becomesclear that under clinical conditions many situationswill arise where the underlying mechanismscan only be guessed. To interpret the effectof neuromuscular blocking drugs clinically it isnecessary to assess contributions due to depolarization,competitive antagonism and presynapticaction produced by the various drugs used.PATTERN OF NEUROMUSCULAR BLOCKAttempts have been made to take advantage of thedifferent susceptibilities of the body muscle toparalysis by neuromuscular blocking drugs bygiving doses which were just enough to paralysethe abdominal muscles without paralysis of theintercostal muscles and diaphragm. However, usefulrelaxation of the abdominal muscles is invariablyassociated with a marked diminution in thetidal volume of respiration. When it is of a minordegree the animal may compensate for this respiratoryimpairment by an increase in respiratoryrate. The breathing which results is characterizedby a pause between inspiration and expiration,producing a rectangular pattern when recordedspirometrically. The increased respiratory rate isaccompanied by over-activity of the diaphragmresulting in very turbulent conditions for intraabdominalsurgery. Larger doses of the neuromuscularblocking agent result in depression whichcannot be compensated for by an increase inrespiratory rate. Because of the oxygen-rich mixturescommonly used in breathing circuits hypoxiamay not occur but, nevertheless, the decreasedminute volume of respiration will lead to an inefficientelimination of carbon dioxide. The results arelikely to be a rising blood pressure, an increasedoozing from cut cutaneous vessels and distressedrespiratory efforts. Thus, it is now generally recognizedthat if a neuromuscular blocking drug isadministered for any purpose some form of artificalrespiration (IPPV) will be required.Sensitivity of muscles to neuromuscularblockThe concept of sensitivity refers to the concentrationof drug at the neuromuscular junction neededto produce a specific degree of blockade. From theearliest attempts to use these drugs it has beenrecognised that the neuromuscular junctions ofvarious muscles differ in response with regard tointensity and duration of blockade. The recentprogress in monitoring and assessing the relationshipbetween the response of different muscles hasnot, unfortunately, been equalled by an understandingof the mechanisms underlying the differentresponses of muscles to neuromuscularblocking agents. If it were available it might allowobjective predictions of the sensitivities of musclesthat are inaccessible to easy monitoring under awide range of pathological states.Among the mechanisms suggested as beingresponsible for differing responses are:1. Perfusion.This is important since neuromuscular blockcan only be produced when the drug binds withacetylcholine receptors at the neuromuscularjunction. Therefore, after i.v. injection the onsettime for the block in any particular muscledepends on circulatory factors such as cardiacoutput and circulation time from injection site tothe muscle, muscle blood flow and proximity tothe central arterial circulation (Donati, 1988). Thisexplains the more rapid onset of paralysis at thediaphragm, laryngeal, masseter, abdominal andfacial muscles which are nearer to the aorta andprobably better perfused than muscles of the distallimbs. For the onset phase concentration gradients

RELAXATION OF SKELETAL MUSCLES 155between the plasma and the receptors are largeand thus perfusion plays a major part in thedevelopment of neuromuscular block. Perfusion,however, does not appear to contribute to unequaldurations of paralysis of different muscles, at leastfor longer acting paralysing drugs (Goat et al.,1976). During recovery from block plasmaconcentration changes slowly with time, so thatthe concentration gradient between plasma andreceptors on the different muscles is likely to besmall as a result perfusion plays only a minor role,duration of blockade being determined mainly byplasma concentration and sensitivity of eachmuscle.2. Acetylcholine receptor numbers, distribution andtype.The motor innervation pattern of muscles,acetylcholinesterase activity and number anddensity of receptors at end plate regions may allplay a part but it is not known exactly how thesemay contribute to muscle sensitivity toneuromuscular blocking drugs.3. Fibre size in the muscle.In goats there is a direct association betweentime to spontaneous recovery from vecuronium orsuxamethonium blockade and size of fibres in thediaphragm, posterior cricoarytenoideus, thyroarytenoideusand ulnaris lateralis muscles (Ibebunjo& Hall, 1993). This evidence for influence of fibresize is supported by the fact that laryngeal andfacial muscles contain very small fibres whilelarger fibres are found in the diaphragm and stilllarger ones in peripheral muscles, a rank orderidentical to the relative sensitivities of thesemuscles to neuromuscular block (Donati et al.,1990).The respiratory musclesThe anaesthetist is interested in the sensitivity ofthe respiratory muscles to neuromuscular blockingdrugs but there is a paucity of informationrelating to the response of intercostal, abdominaland accessory respiratory muscles to these agents.The upper airway is kept patent and protected bythe laryngeal adductors, laryngeal abductors, themasseter muscle and the muscles of the tongueand pharynx, but again little is known about theirsensitivity to neuromuscular blockade.The diaphragm requires more neuromuscularblocker than a peripheral limb muscle for an identicaldegree of blockade. Monitoring of neuromuscularblockade during recovery is, because of theirrelative sensitivity, clearly best carried out byobserving the responses of peripheral muscles tostimulation of their motor nerves.MONITORING OF NEUROMUSCULARBLOCKThe large variability in onset times, duration anddepth of neuromuscular blockade following agiven dose of a neuromuscular blocking agentmakes it impossible to predict its effect in any individualanimal. It is desirable to monitor blockadeto allow drug dosage to be titrated againstresponse of the individual. Monitoring assessesresponse of a muscle following electrical stimulationof its motor nerve somewhere in the nerve’speripheral course. This does not mean that neuromuscularblocking drugs should not be used in theabsence of monitoring apparatus – they were usedquite safely for very many years before thesedevices became available in clinical practice, buttheir use does, undeniably, add to the ease withwhich the degree of muscle relaxation can becontrolled.PERIPHERAL NERVE STIMULATIONA peripheral motor nerve is stimulated to producea propagated action potential when the electricalpotential inside the fibre is decreased from the normalresting value of −90 mV to a threshold ofaround −50 mV. A peripheral nerve stimulatorachieves this when a sufficient current density isproduced to decrease the potential in the tissuesurrounding the nerve whereby the effectivemembrane potential is decreased to the thresholdvalue. This is most easily achieved when the negativeelectrode of the stimulator is placed closest tothe nerve, for a smaller current is then requiredthan if the positive electrode is nearest. After anerve has been depolarized to produce an actionpotential, it is resistant to further stimulation forits refractory period of some 0.5 to 1.0 ms. Theobserved muscle response following stimulation

156 PRINCIPLES AND PROCEDURESto presynaptic effects of non-depolarizing agentsimpairing release of acetylcholine. Its usefulness inveterinary anaesthesia is limited as the size of theresponse must be quantified against a controlresponse obtained before the administration ofany drug and simple visual inspection of thetwitch is insufficiently accurate for this.Train-of-four (TOF)FIG.7.2 MiniStim nerve stimulator.This is typical of thesmall,hand-held inexpensive nerve stimulators used formonitoring neuromuscular block.of a peripheral nerve is only reliable when thenerve is depolarized once in response to the electricalstimulus, the same number of nerve fibresare stimulated each time and the direct stimulationof muscle fibres is avoided. The duration andshape of the stimulus pulse is important for if theduration of the impulse exceeds the refractoryperiod of the nerve, or a non-square wave impulseis delivered, repetitive nerve stimulation mayoccur. A long stimulus duration is also likely toresult in direct muscle stimulation (Fig. 7.2).Since its description by Ali et al., (1970) the trainof-four (four pulses at 2.0Hz) has become the mostpopular of the methods available to the clinicalanaesthetist to monitor competitive neuromuscularblockade. The method as developed by theseworkers involves recording four twitch responsesevoked in a muscle by supramaximal stimulationof its motor nerve at a rate of 2Hz. The frequencyof 2Hz was adopted to allow maximum separationof individual twitch responses; to avoid fadebetween successive train-of-four (TOF) stimuli, thestimulation should not be repeated at intervals ofless than 12 s. The great advantage of the TOF isthat it is not necessary to establish a controlresponse before the administration of the neuromuscularblocking agent (Cullen & Jones, 1984).The technique is simple and evaluation of theevoked response requires no special equipment.Response of the muscle can be assessed either asthe number of palpable twitches (TOF count) orratio of the fourth and the first response (TOFratio). Fig. 7.3 illustrates the relationship duringrecovery from non-depolarizing blockade.The relationship shown in Fig. 7.4 is relativelyconstant for all the different non-depolarizing1234The single twitchSingle twitch stimulation at slow frequencies hasbeen used extensively to investigate effects of neuromuscularblocking agents in human subjects. Ata stimulus frequency greater than about 0.15 Hzthe response becomes progressively smaller owingControlTwitch height ratio =CurarizedHeight of 4Height of 1FIG.7.3 ‘Train-of-four’ (TOF) stimulation of a motornerve.

RELAXATION OF SKELETAL MUSCLES 157Depolarizing block1 2 3 4Non-depolarizing block2 Hz, and thus stimulation at the higher rate is amuch more sensitive method to indicate a slightblockade. However, tetanic stimulation inducesrecovery in the muscles stimulated so that all subsequentevents are shifted towards normality (Ali& Salvarese, 1976). Moreover, stimulation of thenerve at 50 Hz results in sustained tension whenonly 20–25% of receptors are free, less than the25–30% as indicated by TOF restoration of thefourth twitch. Conflicting views may result fromobservations in different species of animal andstimulation of different muscles.Tetanus1 23 4FIG.7.4 Pattern of responses to TOF stimulation duringrecovery from non-depolarizing neuromuscular block.Twitch height calculated as percentage inhibition of firstresponse to TOF stimulation.agents (O’Hara et al., 1986). A TOF ratio of > 0.5 isgenerally accepted as being compatible with clinicallysafe recovery but a TOF ratio of 0.6 to 0.7 canstill be associated with fade (Drenck et al., 1989). Asthe consequences of missing residual curarizationare more serious than failing to recogzise fullrecovery, the prudent anaesthetist is only satisfiedwith a TOF ratio of 0.8 to 0.9. The fourth twitch issaid to be as strong as the first when 25–30% of thereceptors are free of the blocking drug. Duringdepolarizing neuromuscular blockade, theresponses to TOF stimulation are all of approximatelyequal height. The detection of fade is associatedwith the appearance of a phase II block.The TOF has been used to study suxamethonium(Cullen & Jones, 1980), atracurium (Jones &Brearley, 1985), gallamine and pancuronium(Gleed & Jones, 1982), vecuronium (Jones &Seymour, 1985), pipecuronium (Jones, 1987) androcuronium (Martinez et al., 1996) in dogs, but itsvalue in other animals has been questioned.According to Klein et al.(1988) in halothane anaesthetizedhorses there may be very obvious ‘fade’during 50 Hz stimulation when no fade exists atRepetitive high frequency stimulation of the motornerve where the responses to individual stimulifuse and summate to produce a sustained musclecontraction causes what is known as ‘tetany’. Theabsence or presence of fade due to presynapticeffect of non-depolarizing blockade has beenused to assess adequacy of recovery in orderto judge whether any clinically significant blockadepersists to endanger the life of the animal. Atetanic stimulation of 50 Hz for 5 s stressesneuromuscular function to much the same extentas does maximal voluntary effort and it may bepossible to decide, by visual or tactile means,whether there is any fade in response to tetanicstimulation.A sustained tetanus correlates with a TOF ratioof 0.7 or greater. It seems certain that fade representsinteraction of neuromuscular blockingagents with different sites within the neuromuscularjunction. A site of action at presynaptic nicotinicreceptors or ion channels could impede themobilization and/or release of the transmitter inresponse to repeated stimulation of the motornerve; ion channel block might also be involved.Increased mobilization and release of transmittersubstance occuring following tetanic stimulationin the presence of a neuromuscular blockingagent can cause the magnitude of response to asubsequent stimulus to be enhanced. This istermed post-tetanic facilitation or potentiation.The effect increases with the duration and frequencyof tetanic stimulus and can persist for up to30 minutes. It can lead to underestimation of neuromuscularblock and to avoid it it is necessary to

158 PRINCIPLES AND PROCEDURESdelay further tetanic stimlation for at least twominutes (Brul et al., 1991; Silverman & Brul, 1993).During profound neuromuscular blockadewhen all responses to single twitch, TOF andtetanic stimulation have been abolished, posttetanicfacilitation following a tetanic burst mayallow responses to occur with single twitch stimulation.Post tetanic count (PTC) is the number ofresponses to 1 Hz stimulation 3 s after a 5 s 50 Hztetanus (Viby-Mogensen et al., 1981). The numberof post-tetanic responses is inversely related todepth of blockade: the smaller the PTC the deeperthe neuromuscular block.Double burst stimulation (DBS)The DBS consists of two short lasting bursts oftetanus (2 to 4 pulses at 50Hz) separated by 0.75s.The interval of 0.75 s allows the muscle to relaxcompletely between tetanic bursts, so thatresponse to this pattern of stimulation is two singleseparated muscle contractions perceived as twotwitches. The tetanic bursts fatigue the neuromuscularsynapse more than two single twitches sothat fade is exaggerated. Several diferent combinationsof tetanic stimulation have been used but thepattern known as DBS 3,3 seems the most satisfactory.This consists of three bursts at 50Hz followedby a further three at 50Hz after a 0.75s delay (Fig.7.5). The stimulus pattern is of limited use duringoperations; the larger response to DBS means thatthe first response reappears just before that from20 ms750 msFIG.7.5 Preferred pattern of double-burst stimulation.In each burst three impulses are given at a frequency of 50Hz and the two bursts are separated by 750ms (= 0.75s).TOF stimulation and the second response occursslightly before the fourth response to TOF (Gill etal., 1990) DBS was designed to improve clinicaldetection of residual curarization because it iseasier to compare the strength of the two contractionsto DBS than to compare the strength of thefirst and fourth contractions with TOF ratio.When any nerve stimulator is used, supramaximalstimulation must be employed (e.g. 200to 300 V for 0.3 ms) and results of stimulationshould be observed before neuromuscularblock is induced to ascertain that the placing ofthe electrodes is correct and that twitches canbe obtained. Supramaximal stimulation can beachieved using surface or needle electrodes.Paediatric ECG silver/silver chloride gel electrodesare excellent provided the underlying skinis properly prepared by shaving but needle electrodesmay be necessary in obese animals or thosehaving very thick skins.Recognition of twitches in clinical practiceIn clinical practice the most convenient way ofassessing the response to stimulation of the motornerve is to observe or feel for contraction of muscles.This obviously means that the accurate evaluationof the strength of muscle activity obtained bymechanical recording with a force transducer asemployed in the laboratory, cannot be expected.However, even under laboratory conditions stabilityof recording with time tends to be poor so perhapsthe limitations imposed in the clinicalsituation are not a major drawback. Visualappraisal of the relevant muscle twitch is probablythe simplest way of recognizing the response tonerve stimulation but other means exist.When the ulnar nerve is stimulated accelerographymay be used to measure the acceleration of thedistal limb. The mass of the limb is taken to be constantand by Newton’s law (force = mass × acceleration)changes in force are directly proportional tochanges in acceleration. Fixation of the limb is notcritical and small hand-held accelerograph monitorsare available but these devices are not veryreliable. Slight alteration in the position of the limbmay alter the measured response.Another method of monitoring involves recordingof the electromyogram (EMG) from the stimu-

RELAXATION OF SKELETAL MUSCLES 159lated muscle. This involves insertion of threeneedle electrodes – the active electrode from thebelly of the muscle, a reference electrode onthe point of origin of the muscle and a ground electrodepositioned between the recording and stimulatingelectrodes. The recording signal is gated andusually delayed for 3 to 4ms following nerve stimulationto avoid stimulus artefact. The equipmentis expensive and the technique is usually reservedfor experimental studies.Recognition of paralysis when a nervestimulator is not usedThere can be little doubt that the reliance on simpleclinical evaluations of the degree of neuromuscularblockade (using such criteria as the respiratoryefforts in the anaesthetized animal) is inadequate.There is a remarkably wide variation in the sensitivityof individuals to neuromuscular blockingdrugs but after spontaneous or evoked recoveryfrom neuromuscular blockade routine clinicalmonitoring may allow the prediction of whichindividuals are likely to be able to maintain andclear their airways.Abolition of diaphragmatic activity can betaken to indicate complete muscle paralysis. If ananimal can move its limbs in such a way as to beable to maintain itself in sternal recumbency itusually means that at the most only partial neuromuscularblock is present. Short, jerky respiratoryefforts are often seen in animals where diaphragmaticactivity is not in evidence and marked blockadeexists. To assess the ability of a partiallyparalysed animal to breathe, the endotracheal tubemay be occluded and the negative pressure generatedin the tracheal tube during an attempt at inspirationmeasured with a simple anaeroid manometer.Depending on depth of anaesthesia and the prevailingPaCO 2 , a pressure of −10 to −20cm H 2 O canusually be taken to indicate that the block is insufficientto produce respiratory inadequacy. However,although in these circumstances gas exchange maybe adequate in an animal whose airway is safeguardedby an endotracheal tube, the degree ofneuromuscular block may not leave enough marginof safety after extubation because of residualparalysis of the muscles of the pharynx and larynxcausing upper airway obstruction.FIG.7.6 Site for stimulation of the ulnar nerve in the dogand cat.Sites for electrical stimulation of motornervesIn theory, neuromuscular block can be monitoredby stimulation of any superficially placed peripheralmotor nerve and evaluation of the response ofany muscle supplied by that nerve. Monitoring isusually performed at some site where there is anaccessible peripheral nerve and a readily availablemuscle for assessment of the results of the nervestimulation.The dog and catIn dogs muscle responses to electrical stimulationof the ulnar (Heckman et al., 1977; Cullen et al.,1980), tibial (Curtis & Eiker, 1991), peroneal(Bowen, 1969) and facial (Cullen et al., 1980a)nerves have been reported. Probably the best ofthese, which should be used when accessible duringan operation, is the ulnar nerve. It is stimulatedat its most superficial location on the medial aspectof the elbow and contraction involving theforepaw is assessed visually or by palpation. Theperoneal nerve is stimulated on the lateral aspectof the stifle and muscle twitch of the hindfootassessed; this site is particularly useful when thehead end of the animal is covered, for exampleduring ocular surgery. Accurate recording of muscletwitches is not possible with facial nerve stimulation(Cullen and Jones, 1980a).The horseThe most commonly stimulated nerve is the facialnerve (Fig. 7.7) where it can be palpated on themasseter muscle ventral to the lateral canthus ofthe eye. This produces easily visible contractionsof the muscles of the lip and nostrils (Bowen, 1969;

160 PRINCIPLES AND PROCEDURESJones & Prentice, 1976). The peroneal nerve (Fig.7.8) can be stimulated as it crosses the head of thefibula (Klein et al., 1988) to produce contractions ofthe digital extensor muscles. It is advisable torestrain the hind leg when this nerve is stimulatedeven if no mechanical recording of the response isproposed. In horses and ponies stimulation of theperoneal nerve shows greater sensitivity to neuromuscularblocking agents than the facial muscletwitch (Manley et al., 1983 ; Hildebrand & Arpin,1988; Hildebrand et al., 1989).Other animalsPeroneal nerve stimulation has been used in theassessment of neuromuscular block in cows(Bowen, 1969), calves (Hildebrand & Howitt, 1984)and llamas (Hildebrand & Hill, 1991).Factors affecting monitoringFIG.7.7 Site for stimulation of the facial nerve in thehorse.Some patient conditions and errors in monitoringtechniques can affect the muscle response observedfollowing stimulation of a motor nerve andcan lead to erroneous conclusions being drawn.HypothermiaHypothermia is a common finding during generalanaesthesia and may cause the degree of neuromuscularblock to be overestimated. It is generallyaccepted that there is a 10% decrease in twitchheight per °C, although the TOF ratio shows only aminimal effect. Hypothermia seems to have asmaller and more consistent effect on the EMGcompared to mechanical recording (Engbaek et al.,1992).Reduction in body temperature decreases renal,hepatic and biliary elimination of non-depolarizingdrugs and during hypothermia reduced dosesmay be needed to produce any given degree ofblockade. Below a body core temperature of34.5 °C monitoring may become increasinglyinaccurate as thermoregulatory vasoconstrictionoccurs. Reduction of muscle blood flow inhypothermic animals may lead to delay in theonset of the block and unless allowance is madefor this unduly deep block can result when assessmentis carried out too soon after the injection ofthe drug because the anaesthetist is persuaded toadminister further, unnecessary, doses.FIG.7.8 Site for stimulation of the peroneal nerve in thehorse.The nerve crosses the shaft of the tibia just distal tothe head of the fibula and is often palpable at this site inthin-skinned horses.OverstimulationOverstimulation caused by an excessive currentdirectly stimulating muscle or by inducing repetitivefiring leads to the degree of blockade being

RELAXATION OF SKELETAL MUSCLES 161underestimated. Overstimulation is most likely tofollow when the nerve stimulator is applied afterthe administration of the first dose of neuromuscularblocking agent.AGENTS WHICH PRODUCE NON-DEPOLARIZING (COMPETITIVE)BLOCKd-TUBOCURARINE CHLORIDEA purified, biologically standardized preparationof curare (Intocostrin) was used in dogs in 1951.Intocostrin was, however, a relatively crudesubstance, and the pure quaternary alkaloid,d-tubocurarine, which had become available in1944, was used in the UK and elsewhere. Afterintravenous injection maximum activity is apparentwithin 2–3 minutes and lasts for 35–40 minutesin most species of animal. Some 30–40% of thedose is excreted unchanged in the urine within 3–4 hours. Plasma proteins have the power of bindingd-tubocurarine chloride and full discussion ofthe fate of tubocurarine in the body has been givenby Kalow (1959).Use of an effective dose, i.e. dose that correspondsto 90% depression of twitch response underlight general anaesthesia, showed that in dogsd-tubocurarine chloride has actions other than atthe neuromuscular junction for although evenlarge doses of the drug do not affect the caninemyocardium it causes a severe fall in blood pressureand an increase in heart rate. The fall in arterialblood pressure appears to be due to block ofimpulse transmission across autonomic ganglia –hence tachycardia from vagal block – and/orrelease of histamine. A similar fall in arterial bloodpressure occurs when the drug is administeredintravenously to cats. In pigs, doses of the order of0.3mg/kg cause complete relaxation with respiratoryparalysis without at the same time causing anymarked fall in arterial blood pressure. Althoughunlikely to be of any use in clinical porcine anaesthesia,d-tubocurarine chloride has proved to be auseful agent for the production of relaxationrequired for experimental surgery.Relatively little is known about the action of d-tubocurarine chloride in ruminant animals. Younglambs and calves appear very sensitive to theparalysing action of the drug but doses of up to0.06 mg/kg have been given without harmfuleffects being noted. Intocostrin, the crude curarepreparation, was used in horses during chloralhydrate narcosis and Booth and Rankin (1953)came to the conclusion that this combinationof drugs had no value in equine anaesthesia.However, the dose of curare used (about0.12 mg/kg when expressed in terms of the pured-tubocurarine was much less than what is todayregarded as the minimal effective dose. Doses of0.22 to 0.25mg/kg produce good relaxation withrespiratory arrest in anaesthetized horses breathing0.8 to 1.0% halothane and no significanthypotension is encountered.DIMETHYL ETHER OF d-TUBOCURARINEThe dimethyl ether of d-tubocurarine has beenused as a relaxant during anaesthesia in dogs, cats,pigs and horses. It appeared to be two to threetimes as potent as d-tubocurarine chloride but theduration of neuromuscular blockade was slightlyshorter. It never gained a wide popularity and hasnot been available a in the UK since about 1965 butit is available in the USA under the name of‘Metocurine’.GALLAMINE TRIETHIODIDEGallamine block of cardiac muscarinic activity canbe useful during halothane anaesthesia sincehalothane tends to produce bradycardia via thevagus nerve. Tachycardia occurs within 1.0 to1.5min after i.v. injection and in dogs and pigs theheart rate increases by 10–20%. The rise in heartrate is sometimes accompanied by a rise in arterialblood pressure. It is not detoxicated and is excretedunchanged in the urine. Gallamine does notgive rise to histamine release so that it is a usefulnon-depolarizing relaxant in dogs.In dogs doses of 1.0mg/kg by i.v. injection usuallycause complete relaxation for 15 to 20 minutes.Apart from a slight tachycardia, the drug appearsto produce few side effects, but occasionallyhypertension follows its administration. In cats1.0mg/kg produces apnoea of 10 to 20min duration.Pigs are very resistant to gallamine and dosesof 4mg/kg are needed to produce complete relax-

162 PRINCIPLES AND PROCEDURESation with apnoea. In horses, doses of 0.5 to1.0 mg/kg result in complete paralysis withapnoea of 10 to 20min duration. Young lambs andcalves have been given doses of 0.5–1.0 mg/kgwithout harmful effect but in these animals apnoeamay be prolonged.ALCURONIUM CHLORIDEAlcuronium is not available in the USA. It is diallylnortoxiferine,a derivative of the alkaloid toxiferineobtained from calabash curare. It has beenused quite extensively in dogs and horses andseems to have no significant histamine liberatingor ganglionic blocking effects. During lighthalothane anaesthesia the dose required to producecomplete relaxation with respiratory arrest is0.1 mg/kg. Intravenous injection produces nochange in heart rate, arterial blood pressure or centralvenous pressure. The return of spontaneousbreathing is apparently followed by a prolongedperiod of partial paresis; because of this, reversalof the myoneural block is obligatory. If only onedose of alcuronium chloride has been given duringthe course of an operation, the block is veryreadily reversed with neostigmine or other anticholinesterases,but when more than one dose ofalcuronium has been administered some difficultymay be experienced in antagonizing its effects. Itis, therefore, probably advisable to limit the use ofalcuronium for operations which can be completedin the 70 ± 18 minute period of relaxation whichfollows one injection of the drug (Jones et al., 1978).PANCURONIUM BROMIDEPancuronium bromide, an amino steroid free fromany hormonal action, is a rapidly acting, nondepolarizingneuromuscular blocker with a mediumduration of activity. It has no majorundesirable side effects but its administration maybe followed by a slight, short lived, rise in arterialblood pressure. A study in 1970 of the effects ofpancuronium in dogs, cats and horses (G.M.Thompson, personal communication) showed thatthe i.v. injection of the drug causes minimal changein heart rate or central venous pressure and noalteration of the ECG. During light anaesthesiadoses of 0.06mg/kg have been found to producecomplete relaxation with apnoea in dogs andhorses of about 40 min duration together with ashort-lived rise in arterial blood pressure. A similarperiod of apnoea follows a second dose of0.03 mg/kg. The delay in achieving maximumeffect after i.v. administration is much less than isfound with d-tubocurarine or alcuronium. Completeantagonism with neostigmine (always givenwith an anticholinergic) is readily obtained and nocases of relapse into neuromuscular block havebeen encountered. Care should be taken in dogssuffering from chronic nephritis and other conditionswhich impair kidney function, because it is, inpart, excreted unchanged in the urine and its actionis also prolonged in cases of biliary obstruction.VECURONIUMVecuronium is a monoquarternary analogue ofpancuronium, the only difference in structurebeing that in this compound the nitrogen in thepiperidine group attached to the steroid nucleusis not quarternary and positively charged whereasin pancuronium it is. Due to the instability of the3-acetyl group in high concentrations in solutionthe drug is marketed as a freeze-dried bufferedpowder with water in a separate ampoule. Thepowder can be kept on the shelf at room temperaturewithout deterioration. Vecuronium is currentlythe most specific neuromuscular blockingdrug in clinical use and is more potent and shorteracting than pancuronium. It shows a low propensityto liberate histamine and possesses anegligible ganglionic blocking action, hencecardiovascular side effects are unlikely to be seenduring clinical use.Although the mechanism and exact pathway ofinactivation in the body is not fully understood, byanalogy with pancuronium there are likely to bethree main metabolites that could arise by deacetylationto the corresponding alcohol. The principalmetabolite appears to be the 3-hydroxyl derivativefor up to 10% of an injected dose may appear inthis form in the urine.In dogs doses of 0.06mg/kg produce an initialblock of about 20 min and in horses this doseappears to produce apnoea of 20 to 30 min duration.Although the ED 50 of vecuronium is about0.04 mg/kg compared with 0.05 mg/kg for

RELAXATION OF SKELETAL MUSCLES 163pancuronium, at this dose the recovery from neuromuscularblock to 50% twitch depression is lessthan 10min and this period is less than adequatefor most surgical procedures, whereas thatproduced by pancuronium is much longer lasting.As a result, if longer lasting relaxation is to beobtained it is necessary to use a larger bolus doseof vecuronium to produce a rather greater initialblock than with pancuronium.Vecuronium has both hepatic and renal pathwaysfor excretion but renal failure has little effecton its clearance. Biliary excretion accounts forabout 50% of the injected dose so that clearance ismuch reduced in severe hepatic disease. In theabsence of renal and hepatic disease it is notmarkedly cumulative and, indeed, in healthy dogsup to six incremental doses of 0.4 mg/kg havebeen shown to be non-cumulative (Jones &Seymour, 1985). It has also been used as an infusionin dogs (Clutton, 1992).PIPECURONIUMPipecuronium bromide, a long acting non-depolarizingneuromuscular blocking agent, is an analogueof pancuronium. It was originally used in1980 in Hungary but it is now approved for clinicaluse in man in both the UK and the USA. In dogsabout 77% of the injected drug is said to be eliminatedin the urine with less than 5% being excretedin the bile. One potential advantage of pipecuroniumis that it is apparently free from cardiovascularside effects. Its neuromuscular blocking effects in thedog have been investigated (Jones 1987;1987a).ROCURONIUMRocuronium, formerly known as Org 9426, asteroidal non-depolarizing neuromuscular blocker,is a derivative of vecuronium. Initial animal studies(Muir et al., 1989 ; Cason et al., 1990) demonstratedthat compared with vecuronium the onsetof block was more rapid, its duration of action verysimilar and its potency about one-fifth. It has no orminimal cardiovascular effects but in anaesthetizedcats it has been shown to possess avagal/neuromuscular blocking ratio of 7 comparedto 3 for pancuronium (Marshall et al., 1994),so that compared to vecuronium it may be consideredto have some mild vagolytic activity. In catsmore than 50% of the injected dose is eliminatedunchanged in the bile and only 9% in the urine(Khuenl-Brady et al., 1990). No signs of histaminerelease or anaphylactoid responses have beenreported after its administration but it has beenreported that in man the injection of rocuronium ispainful and, therefore, the drug should only beinjected after the deeper stages of anaesthesia havebeen achieved (Borgeat & Kwiatkowski, 1997).ATRACURIUMAtracurium besylate is a bisquaternary isoquinolinecompound and is available as a mixture of10 sterioisomers (Amaki et al., 1985). It is eliminatedby pH and temperature-dependent Hofmanndegradation, giving rise to laudanosine and amonoquaternary ester which is further degraded toa second laudanosine molecule and an acrylateester (Stenlake et al., 1981). None of these degraduationproducts is active at the neuromuscularjunction. The half-life of this process in cats is about19 minutes (Payne & Hughes, 1981). Coupled withuptake by the the liver, kidney and other tissues,this produces a rapid plasma clearance and anapparent large distribution volume. The Hofmanndegradation process does not need an enzyme systemand attains a linear relationship between thedose of drug and the rate of metabolism irrespectiveof the substrate load. Obviously, the reasonwhy the duration of block is unaffected by hepaticdisease or anuria is because neither process involvesliver metabolism or renal excretion.Because of its propensity to release histamine,atracurium cannot be administered in multiples ofits ED 50 to give the same sort of flexibility of durationof action associated with vecuronium where alarge single bolus dose can be used to providerelaxation for a moderately prolonged operation.It is in short procedures that its relatively rapidonset, medium duration of action and rapid recoveryare most useful.The paralysing dose for the dog is from 0.3 to0.5 mg/kg (Jones & Clutton, 1984) and recoveryfrom these doses occurs in about 40 min (Joneset al., 1983) although there is a very wide range inthe duration of effect. The reason for this widevariability in duration is unknown. The drug has

164 PRINCIPLES AND PROCEDURESalso been administered to dogs by continuousinfusion of 0.5mg/kg/hour after a loading dose of0.5mg/kg (Jones & Brearley, 1985).A single injection of 0.11 mg/kg of atracuroniumproduces paralysis of about 20 to 30 minduration in halothane anaesthetized horses(Hildebrand et al., 1986). It has also been administeredby infusion to horses under halothane anaesthesia(Klein et al., 1988). After a loading dose of0.05 mg/kg in another investigation a 95 to 99 %reduction in TOF hoof-twitch response was producedby an infusion of 0.17 ± 0.01 mg/kg/hour(Hildebrand & Hill, 1989).Some anxiety has been expressed about a possiblecentral nervous system effect of the tertiarymetabolite of atracurium. This compound, laudanosine,does penetrate the blood–brain barrierand, in higher concentrations than are likely to beproduced with clinical doses in normal animals, itcan cause analeptic or convulsant effects. To date,no reports of these effects have been described inthe veterinary literature.MIVACURIUMSavarese and colleagues in Massachusettsinvestigated a series of compounds which are nondepolarizingand metabolized by plasma cholinesterase.One of these, mivacurium, is abenzylisoquinoline diester compound with apotency approximately one third to one half that ofatracurium. It consists of three sterioisomers ofwhich one is active. Unlike atracurium, its breakdownproducts are pharmacologically inactive.Breakdown is by plasma cholinesterase and bothacetylcholinesterase and spontaneous hydrolysisappear to have only minimal effects. Low plasmacholinesterase levels are associated with a longerduration of action and a decreased plasmacholinesterase due to hepatic failure results in prolongedactivity, although alternative pathways forclearance are available (Saverese et al., 1988).Re-establishment of paralysis using very smalldoses of mivacurium following apparent fullrecovery from mivacurium-induced neuromuscularblock has been reported in man (Kopman et al.,1996). Even at a TOF of 0.95 the neuromuscularjunction’s margin of safety remains considerablyreduced.PHARMACOKINETICS OF THENON-DEPOLARIZING AGENTSAll neuromuscular blocking agents contain quaternaryammonium groups making them positivelycharged at body temperature. Because of thisionization they are highly water soluble and relativelyinsoluble in fat. Their pharmacokinetics canbe described by a two or three compartmentmodel, with a rapid distribution phase in whichthey distribute from a central into a peripheralcompartment. This is followed by one or twoslower elimination phases, consisting of biotransformationand excretion. For most drugs atwo compartment model is suitable and thus twohalf-lives can be determined: the half-life of distribution(t 1/2α ) and the half-life of elimination(t 1/2β ). The mean residence time (MRT) has beenintroduced for statistical purposes – the time for63.2 % of the administered dose to be excreted. Thevalue known as C ss95is the plasma concentrationat which a 95% decrease in muscle contractionoccurs. This is particularly important to the anaesthetistbecause it represents the surgically optimallevel of neuromuscular block.All pharmacokinetic data are relevant to the fullunderstanding of the pharmacological profile of adrug under particular circumstances, but only afew are of immediate clinical importance to theanaesthetist who principally wishes to utilizethem for calculation of the appropriate infusionrate for any particular drug. These clinicallyimportant data are summarized in Table 7.1 whichshows mean figures culled from the literature. Thepublished data show a marked variability resultingfrom differences in the doses administered, theanaesthetic technique employed, the time ofsampling, the extraction and assay methods formeasuring the concentrations, the species of animaland in the pharmacokinetic model used forthe calculations.Vd c governs the peak plasma concentration followinginjection of a bolus dose. Because drug distributiondepends on tissue perfusion, cardiacoutput is an important factor in pharmacokinetics.Reduction in cardiac output leads to slow and lesserdistribution with lengthening of t 1/2α , a sloweronset of action and eventually, a stronger effect.With increased cardiac output tissue perfusion is

RELAXATION OF SKELETAL MUSCLES 165TABLE 7.1 Pharmacokinetic data (rounded figures).Vd c = initial volume of distribution;Vdss = volume ofdistribution,central and peripheral compartment;Clp = plasma clearance;t 1/2 β = half-life of elimination;MRT = mean residence time;C ss95 = plasma concentration for 95 % decrease in first twitch of TOFDrug C ss95 (mg/kg) Vd c (l/kg) Cd ss (1/kg) Cl p (ml/kg/min) t 1/2 β (min) MRT (min)Alcuronium 0.08 0.15 0.33 1.34 143Atracurium 1.30 0.05 0.20 6.60 21Doxacurium 0.22 2.76 99 91.9Gallamine 10.00 0.10 0.20 1.20 134Metocurine 0.60 0.05 0.57 1.20 360Mivacurium 0.11 70.00 18 1.5Pancuronium 0.35 0.10 0.26 1.80 132 134.0Pipecuronium 0.11 0.31 2.30 137 140.0Rocuronium 0.04 0.21 3.70 97 58.3Vecuronium 0.23 0.07 0.27 5.20 71 52.0greater than normal which means a more extensiveand faster distribution and thus a higher dose isneeded to cause the same effect. When the plasmaconcentration of a drug to produce a given level ofneuromuscular block (e.g. C ss95 ) is known, the singlebolus dose or the rate of a continuous infusionneeded for it to be achieved can be calculated:Bolus dose = C ss95 × Vd ss ,and infusion rate = C ss95 × ClpIt must be remembered, however, that a wide biologicalvariability in response to neuromuscularblocking drugs exists between individual animals.Another important factor in pharmacokineticbehaviour is protein binding which influences thevolume of distribution, metabolism and excretionof neuromuscular blocking agents. Changes inplasma protein concentration in diseased statesand binding of concurrently administered drugswill both influence the protein binding of theseagents.AGENTS WHICH PRODUCEDEPOLARIZING BLOCKMuscle paralysis due to depolarization differsfrom that caused by non-depolarizing drugs in thefollowing respects:1. The paralysis is preceded by the transientstimulation of muscle fibres, probably caused bythe initial depolarization. The muscle twitchingwhich results from this is visible in animalsubjects.2. Substances which antagonize the non-depolarizingagents tend to potentiate the depolarizingones and thus in clinical practice it is important tonote that anticholinestrases such as neostigminemay prolong the action of depolarizing relaxants.3. In a nerve–muscle preparation it can bedemonstrated that after partial paralysis with anon-depolarizing drug there is a rapid decay of aninduced tetanus, whereas after a correspondingdegree of paralysis caused by a depolarizing agentan induced tetanus is sustained.4. It is unlikely that depolarizing agents everproduce a pure type of neuromuscular block. Forexample, in dogs they cause both depolarizationand desensitization.5. In the cat, rat and mouse, the depolarizingagents affect the red muscles more than the white,whereas non-depolarizers have the oppositeeffect.In certain animal species esters of choline, notablythe succinyl derivatives, cause neuromuscularblock of short duration by depolarization. Two ofthese compounds are dimethylsuccinylcholineand diethylsuccinylcholine. The former substanceis known as suxamethonium and the latter as suxethonium.They resemble each other pharmacologically,with the sole difference that the paralysiscaused by suxethonium is rather more rapid inonset and of slightly shorter duration. The firsttwo of the compounds to be used clinically in veterinaryanaesthesia was suxethonium bromide(Hall, 1952) but the suxamethonium compound isthe one generally employed today.

166 PRINCIPLES AND PROCEDURESSUXAMETHONIUMSuxamethonium consists of two acetylcholinemolecules coupled back to back. Like acetylcholine,it is hydrolysed by cholinesterases andthis hydrolysis is believed to be responsible forrecovery from its effects. It has been shown in dogsthat the injection of a purified cholinesterasepreparation produces a marked increase in resistanceto the effect of the drug (Hall et al., 1953).Because of this, attempts have been made to correlatethe sensitivity of an animal to suxamethoniumwith the levels of cholinesterase present in itsblood (Stowe et al., 1958).The ability of plasma cholinesterase to hydrolysebutyrylthiocholine can be used to predict sensitivityto suxamethonium in man but has not been of valuein animals. Faye (1988) has made an extensive studyof the role of cholinesterase in the explanation ofdiffering species sensitivity to suxamethonium. Inher opinion the affinities of cholinesterase for differentsubstrates are different between species (Tables7.2 and 7.3) and, furthermore, although the hydrolysisof some assay substrates parallel that of suxamethoniumin man they do not in other species ofanimal. Therefore, the substrates used to studycholinesterase activity in man cannot be used todraw conclusions regarding suxamethonium sensitivityin other animals; for this to be done, Faye considersit is most important that the substrate usedfor assay is suxamethonium itself.In birds, suxamethonium produces spasticparalysis of the whole body. An initial enhancementof the twitch produced by stimulation of themotor nerve is quickly followed by a tonic contractionand depression of neuromuscular transmission.Spasm does not require neural impulses,usually prevents muscle fasciculation and persistsas long as the block lasts. In mammals, thismyotonic response persists in the extraocular muscles,in partially denervated and degeneratinglimb muscles and to a minor degree in the jawmuscles. Animals susceptible to malignant hyperthermiaalso respond to suxamethonium with aspastic paralysis.In domestic animals there is some slight variationin response of the various muscle groups butthe diaphragmatic muscle is usually the last to beaffected. Suxamethonium causes marked musclefasciculation and in man these contractions frequentlylead to muscle pains obvious the next dayto the patient. Conscious volunteers given suxamethoniumfor experimental purposes have reportedthat the muscle fasciculations are extremelypainful. Suxamethonium produces actual muscleinjury; serum creatine kinase levels are raised andmyoglobinuria has been seen after intermittentadministration of the drug during halothaneanaesthesia in horses.Because cholinesterase is formed in the liver,the existence of severe liver damage, cachexia, ormalnutrition may prolong the duration of action ofsuxamethonium. In man, atypical forms of cholinesteraseare recognized. They have been foundin animals but their significance and mode ofinheritance have not been determined (Trucchiet al, 1988). Low cholinesterase levels are alsoTABLE 7.2 Mean values for plasma cholinesterases as determined by the use of different assay substrates(courtesy of Dr Sherry Faye,Senior Biochemist,Bristol Royal Infirmary)Species Propionyl thiocholine Benzoyl choline Butyryl thiocholine SuccinylcholineSacred baboon 4.20 0.85 7.01 89.70Chimpanzee 5.65 0.93 6.15 76.50Bottle-nosed dolphin 0.04 None 0.02 47.90Pig 0.34 0.03 0.32 43.13Horse 4.18 0.27 4.46 33.10Dog 2.13 0.36 3.33 8.01Cat 1.36 – – 7.24Indian elephant 0.01 None 0.05 7.00Goat 0.14 0.04 0.02 6.70Sheep 0.05 None None 1.47Cow 0.06 – – 0.95

RELAXATION OF SKELETAL MUSCLES 167TABLE 7.3 Plasma cholinesterase activities determined using different substrates expressed as apercentage of appropriate mean human reference range.Mean cholinesterase activity for human Eluhomozygotes taken as:propionylthiocholine activity 4.58units/ml,benzoylcholine activity 0.88units/ml,butyryl thiocholine activity 5.04units/ml and succinylcholine activity 58.6units/ml (courtesy ofDr Sherry Faye,Senior Biochemist,Bristol Royal Infirmary)Species Propionyl thiocholine Benzoyl choline Butyryl thiocholine Succinylcholineactivity activity actvity activityRed deer 1.3 4.5 0.5 6.8Goat 2.9 4.5 0.5 6.7Fallow deer 1.0 – 1.3 12.4Bottle-nosed dolphin 0.9 – 0.4 81.7Indian elephant 0.2 – 0.9 11.9Sacred baboon 91.7 96.6 139.1 153.1Patas monkey 9.2 5.7 13.5 45.9White rhino 29.7 12.5 34.3 26.4Donkey 99.3 62.5 124.4 61.6Muscovy duck 8.5 7.9 6.9 18.9encountered after exposure to organophosphoruscompounds.Suxamethonium, containing two acetylcholinemolecules, might be expected to have actions inthe body in addition to its effects at the neuromuscularjunction and this is indeed the case. Injectionof suxamethonium causes a rise in blood pressurein all animals, although in some species the risemay be preceded by a fall. In cats there is an immediatemarked fall in arterial blood pressure, followedby a slower rise to above the resting level.The fall in blood pressure can be prevented by theprior administration of atropine, and the rise byhexamethonium so that the prior administrationof both these drugs prevents any blood pressurechange. Blood pressure changes are seen after eachsuccessive dose of suxamethonium but with progressivelydiminishing severity. Pulse rate changesare variable, both bradycardia and tachycardiabeing observed, sometimes in the same animal,and often the heart rate does not change. In horsesand dogs the nicotinic response predominates(Adams & Hall, 1962, 1962a) – very occasionally afall in blood pressure with bradycardia is seen, butan increase in both blood pressure and heart rate isthe usual response.Cardiac arrhythmias are frequently seen after i.v.injection and usually take the form of atrioventricularnodal rhythm. One injection of suxamethoniumcauses a rise in serum potassium which is notabolished by adrenalectomy, ganglionic blockade,adrenolytic drugs or high epidural block so it islikely to be due to release of potassium ions frommuscle. This rise in serum potassium may also beassociated with cardiac irregularities. Prolongedadministration of suxamethonium, on the otherhand, causes a large decrease in serum potassiumin dogs, but the reason for this is unknown(Stevenson, 1960).There are wide species differences in sensitivityto the neuromuscular blocking action of suxamethonium.Horses, pigs and cats are relativelyresistant, but dogs, sheep and cattle are paralysedby small doses. In horses 0.12–0.15mg/kg usuallycause paralysis of the limb, head and neck muscleswithout producing diaphragmatic paralysis. Inmost horses double this dose will cause total paralysisbut the exact effect produced in any individualwill depend on the depth of anaesthesia at thetime when the relaxant is administered. After asingle dose paralysis generally lasts for about4–5 min although limb weakness may persist forsome time longer. In cattle, one-sixth of this quantity(0.02 mg/kg) produces paralysis of the bodymuscles without diaphragmatic paralysis and thisrelaxation lasts 6–8 min. Once again, double thisdose will cause complete paralysis in most animals.In sheep, doses similar to those used in cattleare employed. Pigs require much larger doses; tofacilitate endotracheal intubation the doserequired is about 2mg/kg, which produces completeparalysis for only 2–3min. In cats, 3–5mg of

168 PRINCIPLES AND PROCEDURESsuxamethonium chloride (total dose) produces5–6 min of paralysis. The dog is comparativelysensitive and doses of 0.3 mg/kg produce totalparalysis of 15–20minutes’ duration. A single dosemay produce phase II block in dogs and phase IIblock may also be produced when more than onedose is given to other animals. It is believed thatthe response of the motor end plate graduallyalters with each successive dose but the precisetime and dose relationship is not yet known.Apart from its use to facilitate endotrachealintubation in pigs and cats, it seems that there aretoday no good indications for suxamethonium inveterinary anaesthesia.FACTORS AFFECTING THE ACTION OFNEUROMUSCULAR BLOCKING DRUGSFactors such as age, concurrent administration ofother drugs, body temperature, extracellular pH,neuromuscular disease and genetic abnormalitiesmay influence response to muscle relaxant drugs.AgeThe response of young animals to neuromuscularblocking drugs is different from that of adults. Themuscles of a 7-day-old kitten are less sensitive todepolarizing drugs than those of a normal adultcat but very sensitive to tubocurarine. The anaestheticdrugs themselves have an age-dependenteffect upon neuromuscular transmission so thatcomplementary relaxation provided by someanaesthetics is variable and important.Body temperatureThe effect of muscle and body temperature on thepotency and duration of action of muscle relaxantsis difficult to assess because any effect of change inbody temperature on neuromuscular block may becomplicated by changes in regional blood flow.Reduction in body temperature decreases renal,hepatic and biliary elimination of non-depolarizingneuromuscular blocking agents and duringhypothermia reduced doses may be needed to producea given degree of neuromuscular block. Inclinical practice it certainly seems that the requirementsof non-depolarizing agents are decreasedduring moderate hypothermia. Reduction of muscleblood flow in hypothermic animals may lead todelay in onset time of block and unless allowanceis made for this, gives rise to the risk of seriousoverdosing if the drug is being given in incrementaldoses to assess its effects as administrationproceeds.Administration of other drugsAny drug which has anticholinesterase propertieswill prolong the action of suxamethonium andtend to antagonize non-depolarizing neuromuscularblockade. Several antibiotics, especially theaminoglycosides, may produce or enhance nondepolarizingblock, possibly by binding calcium toproduce hypocalcaemia, or by influencing bindingof calcium at presynaptic sites. However, antibioticinduced or enhanced competitive block is notinvariably antagonized by anticholinesterasedrugs or by administration of calcium. Careshould, therefore, be taken over the administrationof antibiotics such as gentamycin during theimmediate recovery period following antagonismof non-depolarizing neuromuscular blockersbecause refractory paralysis may occur.General anaesthetics may have a marked effecton neuromuscular block. Halothane, methoxyfluraneand isoflurane potentiate non-depolarizingrelaxants such as pancuronium. Rocuronium blockis potentiated by isoflurane and enflurane but onlyto a lesser degree by halothane.Extracellular pHHypercapnia augments tubocurarine block andopposes its reversal by neostigmine. Alcuroniumand pancuronium block are apparently unaffectedby PCO 2 , but block due to suxamethonium may bepotentiated by acidosis. A number of explanationshave been advanced to account for these findingsand it seems likely that factors such as proteinbinding, ionization of the relaxant and ionizationof the receptor sites may be important.Neuromuscular diseaseAnimals suffering from myasthenia gravis areresistant to depolarizing neuromuscular blockers

RELAXATION OF SKELETAL MUSCLES 169and are more than normally sensitive to competitiveblocking agents. A myopathy has beendescribed in a horse (Jones & Richie, 1965) where ageneralized muscle spasm was produced by theadministration of an extremely small dose of suxamethonium.Genetic factorsGenetic factors in relation to response to suxamethoniumhave been described in humans. Trucchiet al. (1988) have demonstrated some effects oncholinesterase activity which seem to have a geneticbasis in dogs.Blood pressure and flowRecovery from the effects of relaxant drugs is likelyto be more rapid if blood flow through themuscle is high and thus maintains a steep concentrationgradient between tissues and blood byremoving molecules of the agent as soon as theyare freed from receptors.Electrolyte imbalanceA deficiency of calcium, potassium or sodiumretards the depolarization of motor end plates andby thus inhibiting neuromuscular transmissionwill increase the blocking effects of the non-depolarizingmuscle relaxants. On the other hand,hyperkalaemia and hypernatraemia render musclesmore resistant to them.EVOKED RECOVERY FROMNEUROMUSCULAR BLOCKWhile it is possible for non-depolarizing agents tobe eliminated from the body with or without significantmetabolism, thus resulting in terminationof action, this can never be reliably predicted.There is great individual variation in response ofanimals to neuromuscular blocking drugs and, inaddition, with many drugs spontaneous recoverytakes a very long time. Thus, antagonism of nondepolarizingneuromuscular block is usually indicatedin routine clinical practice – especially inhorses, for these animals appear to have a psychologicalneed to stand immediately on recoveryfrom anaesthesia. The presence of even a smalldegree of neuromuscular block can result in violentexcitement and floundering about as the horsetries, unsuccessfully because of muscle weakness,to get to its feet.The principle underlying use of antagonists toneuromuscular blocking drugs is tilting of the balancebetween the concentration of acetylcholineand the concentration of the drug at the neuromuscularjunction in favour of the former. To do this, itis necessary to reduce breakdown of acetylcholineby cholinesterase or to facilitate greater release ofit. The drugs that are in common use as antagonistsof neuromuscular block are those that reducebreakdown of the transmitter, i.e. they are anticholinesterases.The anticholinesterases allow theaccumulation of acetylcholine at the end plateregion but acetylcholine does not actively displacethe neuromuscular blocking drugs molecules fromthe receptor sites. There is constant attachmentand reattachment of the molecules of the musclerelaxant and acetylcholine to the receptor, andwith the greater numbers of acetylcholine moleculesfrom inhibition of acetylcholinesterase thereis a greater chance of one of the acetylcholine moleculesoccupying a temporarily ‘unblocked’ receptor(Bowman, 1990).There are no effective antidotes to those agentswhich act by depolarization, but certain anticholinesterasesare effective antidotes to the phaseII block following the use of suxamethonium. It isessential to observe clear fade of TOF because,when phase II block is not present, prolongedparalysis requiring several hours of ventilatorysupport may result from anticholinesterase administration.The commonly used anticholinesteraseagents are neostigmine, edrophonium and pyridostigmineand of these neostigmine is by far themost popular. The use of these agents in the reversalof neuromuscular blockade in veterinary anaesthesiawas well reviewed by Jones (1988).Acetylcholinesterase has two sites of action, oneionic and and the other esteratic, and its inhibitorsare usually classified as acid-transferring or prosthetic.Neostigmine and pyridostigmine are acidtransferringdrugs, containing a carbamate groupand combining with cholinesterase in almostthe same way as acetylcholine.The bond of the

170 PRINCIPLES AND PROCEDUREScarbamate–enzyme is much longer lasting thanthat of the bond of the enzyme with acetylcholineand they are, therefore, more slowly hydrolysedthan acetylcholine, thus preventing the access ofthe enzyme to acetylcholine. Their breakdownproducts also have weak anticholinesterase activity.Prosthetic inhibitors such as edrophoniumhave a dissociation half-life which is much shorterthan that of the neostigmine–enzyme bond but,unlike neostigmine, edrophonium is not metabolizedwhen combined with cholinesterase andis therefore free to recombine repeatedly withthe enzyme (Wilson, 1955). The inhibition ofacetylcholinesterase, although it is the main one, isnot the only action of these drugs. Their otheractions include a direct stimulation of the receptoras well as a presynaptic effect involving enhancementof acetylcholine release (Riker & Wescoe,1946; Deana & Scuka, 1990).Neostigmine and pyridostigmine differ fromedrophonium in their effects on presynaptic receptors.Presynaptic effects of edrophonium are muchgreater in terms of acetylcholine liberation. This isshown by greater anti-fade effect (higher TOFratio) when administered for reversal of neuromuscularblock, fade being a presynaptic phenomenonrelated to liberation of more acetylcholine(Donati et al., 1983). Edrophonium may also differfrom neostigmine and pyridostigmine because itsinconsistent effect in deep neuromuscular blockmay result, at least in part, from a direct depressionof the end plate channel leading to muscleweakness from accumulation of acetylcholine producedin excess due to a presynaptic effect of edrophonium(Wachtel, 1990).If the anticholinerestases are administered inthe absence of non-depolarizing neuromuscularblocking drug they produce muscle fibrillation orfasciculations and, given in large enough doses,they will produce a depolarization type of neuromuscularblock.NEOSTIGMINENeostigmine is probably the most widely usedanticholinesterase antagonist of non-depolarizingneuromuscular block. The time course of theantagonising effect of neostigmine is roughly halfwaybetween that of edrophonium and pyridostigmine,being about 7 to 10 minutes. Unless neuromuscularblock is being monitored by a motornerve stimulation technique, neostigmine shouldnever be given until there is some sign of spontaneousrespiratory activity, otherwise there is noway of assessing its effects and the possibility ofpassing from a non-depolarization to a depolarizationblock exists. An anticholinergic should alwaysbe given to counteract the more serious muscariniceffects of neostigmine (bradycardia, salivation,defaecation and urination). Atropine sulphate maybe mixed in the syringe with neostigmine and themixture given in small repeated doses until fullrespiratory activity is established or monitoringreveals a satisfactory TOF ratio. It is customary tomix atropine and neostigmine in the ratio ofapproximately 1 : 2 (e.g. 1.2 mg of atropine with2.5mg of neostigmine). This practice is quite safebecause anticholinergics exert their effects beforethe onset of neostigmine activity.Neostigmine, even if given with full doses ofatropine, may cause serious cardiac arrhythmias ifthere has been gross underventilation duringanaesthesia or if CO 2 has been allowed to accumulateat the end of operation with a view to ensuringreturn of spontaneous respiration. Hypercapniaalso increases the neuromuscular block of nondepolarizingagents and so antagonism is likely tobe less effective under these conditions. It has beenshown that after anaesthesia in which IPPV hasbeen used to lower the PaCO 2 , spontaneousbreathing returns at low PaCO 2 s, provided that nodepressant drugs have been used. This is probablydue to the effect of stimuli arising in the tracheaand bronchi, skin and, perhaps, to the effect of asudden increase of afferent nerve impulses resultingfrom the return of proprioceptive activity asmuscle tone is restored following the administrationof neostigmine.In the absence of facilities for monitoring ofneuromuscular block reliance must be placed onclinical signs to assess when reversal is adequate.Signs of residual neuromuscular block include trachealtug, paradoxical indrawing of intercostalmuscles during inspiration similar to that seen incases of respiratory obstruction, and a ‘rectangular’breathing pattern in which the inspiratoryposition is held for some time before expirationbegins. The atropine-neostigmine mixture should

RELAXATION OF SKELETAL MUSCLES 171be given in small doses, with a pause betweeneach, until these signs disappear.EDROPHONIUMEdrophonium is an effective and reliable anatagonistto the non-depolarizing agents. Earlier impressionsthat its effects were too short lasting wereprobably due to use of inadequate doses and, withthe use of higher doses, the drug is now becomingpopular. Doses of edrophonium in excess of0.5 mg/kg appear similar in effect to that of neostigminebut the onset of action is considerablyshorter (about 1 to 3 minutes) making it easier totitrate more accurately its administration to fullreversal of blockade. It is usual to administer it inconjunction with atropine or glycopyrrolatealthough it may have fewer and more transientmuscarinic effects than neostigmine.PYRIDOSTIGMINEIn the USA pyridostigmine has found favour insome centres. It has a longer duration of actionthan neostigmine but its long onset time of around10 – 15 minutes means that assessment of reversalis difficult if it is administered by a titrationmethod. In veterinary practice, it appears to haveno significant advantages over neostigmine.4-AMINOPYRIDINEThis has not been used to increase the output ofacetylcholine at nerve endings since the early1980s. The main problems with 4-aminopyridineare its occasional inability to antagonize nondepolarizingneuromuscular block, and its effectson the central and peripheral nervous systems. Itscentral effects may be useful as an analeptic andrespiratory stimulant but other and more satisfactorydrugs exist for these purposes.USE OF NEUROMUSCULARBLOCKING DRUGS IN VETERINARYANAESTHESIAINDICATIONSThe general indications for the use of these drugsin veterinary clinical practice are:1. To relax skeletal muscles for easier surgicalaccess.2. To facilitate control of respiration duringintrathoracic surgery.3. To assist in reduction of dislocated joints.Clinical experience shows that not only aredislocations more easily reduced if the muscles areparalysed but also that reluxation of the joint isfacilitated by the absence of muscle tone. Thereduction of fractures, on the other hand, is seldomeased by administration of relaxants since thedifficulties of reduction are due to spasm ofmuscles around the fracture site provoked byhaematomata and broken bone fragments.4. To limit the amount of general anaestheticused when muscle relaxation itself is not the primerequisite. For example, in dogs no musclerelaxation is needed for operations on the ear canalbut surgical stimulation can be intense, resultingin head shaking unless the animal is very deeplyanaesthetized. The judicious use of neuromuscularblock prevents head shaking by weakening neckmuscles so very much smaller quantities ofanaesthetic or analgesic can be employed. In thesecircumstances all that is required is a light degreeof unconsciousness coupled with analgesia, andthus the detrimental effects of deep depression ofthe central nervous system are avoided.5. To ease the induction of full anaesthesia inanimals already unconscious from intravenousnarcotic drugs. For example, when thiopentone isused to induce loss of consciousness in horsesbefore administration of an inhalant such ashalothane or isoflurane, there is a period when theeffect of the thiopentone is waning and the uptakeof the inhalation agent is not yet sufficient toprevent movement of the limbs. The careful use ofsmall doses of relaxant can do much to ‘smoothout’ this transitional period by paralysing the limbmuscles.6. To facilitate the performance of endotrachealintubation and endoscopy. Although animals canbe intubated without the use of these drugs, theymay make endotracheal intubation very mucheasier, especially in cats and pigs.7. To reduce the need for postoperativeanalgesics. By making surgical access easierwithout forcible retraction of muscles by thesurgeon they minimize bruising of muscle caused

172 PRINCIPLES AND PROCEDURESby retractors. Much postoperative pain is due tomuscle damage and minimizing this by use ofneuromuscular blocking drugs contributes greatlyto postoperative comfort of the animal and towound healing.8. To facilitate eye surgery by ensuringimmobility of the eyeball.CONTRAINDICATIONSIt must be very clearly understood that a relaxantshould never be administered unless facilities areavailable for immediate and sustained artificialrespiration to be applied. The administration ofeven small doses of these drugs may, on occasion,be followed by respiratory paralysis. An animalcannot be ventilated efficiently for very long byapplication of intermittent pressure to the chestwall and artificial respiration must be carried outby application of intermittent positive pressure tothe airway through an endotracheal tube – the useof a face mask, except in an emergency when intubationattempts fail, is not really satisfactorybecause it is all too easy to inflate the stomach aswell as the lungs.In addition it must be clearly recognized thatneuromuscular blocking drugs have no narcotic oranalgesic properties. During any surgical operationan animal must be incapable of appreciatingpain or fear throughout the whole period of actionof any neuromuscular blocking drug which maybe employed. Fortunately, provided due care istaken, it is a relatively simple matter to ensure this,but any doubt about the maintenance of unconsciousnessmust constitute an absolute contraindicationto the use of neuromuscular blockers. Whenan inhalation anaesthetic such as halothane, isofluraneor sevoflurane is being used, with or withoutnitrous oxide, administration of 1.2 × MAC shouldalways ensure unconsciousness without producingan undesirable depth of unconsciousness.TECHNIQUE OF USEInduction of anaesthesia by intravenous medicationis simple and pleasant for the animal sothat heavy sedation with large doses of sedative/analgesic drugs is neither necessary nor desirable.When, however, the use of an intravenous inductionagent is deemed contraindicated andanaesthesia is induced with an inhalation agent,somewhat heavier sedation is required. The neuromuscularblocker may be given at induction orlater, at the start of, or during surgery, dependingon the reason for its use. Atropine or glycopyrrolateshould always be given to avoid troublesomesalivation and increased bronchial secretion whichmay otherwise follow administration of suxamethonium.Induction of anaesthesia with an i.v. drug hasvery few contraindications provided that onlyminimal doses are employed. The dose usedshould only be just sufficient to induce loss of consciousnessand relaxation of the jaw muscles.Dogs, horses and ruminants may then be intubated.In cats and pigs injection of the induction agentmay be followed immediately unconsciousnesssupervenes by i.v. injection of a neuromuscularblocking agent and the animal allowed to breatheO 2 through a close-fitting face mask until respirationceases and atraumatic endotracheal intubationcan be performed. These animals are perhapsbest intubated under suxamethonium-inducedrelaxation but pigs may be intubated undervecuronium paralysis (Richards et al., 1988).Endotracheal intubation is most desirable whenrelaxant drugs are used because a perfectly clearairway is required at all times (but it must never beassumed that the presence of an endotracheal tubenecessarily guarantees an unobstructed airway).Owing to relaxation of pharyngeal and oesophagealmuscles stomach contents may be regurgitatedand aspirated into the lungs. This need notimply that a cuffed endotracheal tube is essential.In cats and other small animals, reasonably closefittingplain tubes confer a considerable protectionfor with IPPV escape of gas around the tube duringthe inspiratory phase discourages the passageof regurgitated stomach contents down the tracheaand the presence of stomach content in thepharynx, from where it can be removed by suction,will become obvious to the observant anaesthetist.If an endotracheal tube is not used the stomachand even the intestines may be inflated by gasforced down the oesophagus when positive pressureis applied to the airway at the mouth and nostrils.This may be dangerous and is always anuisance in abdominal surgery. Laryngeal masks

RELAXATION OF SKELETAL MUSCLES 173(Colgate Medical, Windsor, Berkshire), now widelyused in man instead of endotracheal intubation,may not provide total airway protection in animals.Although tried in pigs they have not beenextensively tested in animals and, currently, thewider exploration of their use in veterinary anaesthesiais precluded by their cost.Maintenance of anaesthesia involves theadministration of further doses of the neuromuscularblocker whenever these are indicated, andensuring beyond all reasonable doubt that theanimal remains lightly anaesthetized throughoutthe operation. Indications for supplementarydoses of relaxant are relatively easy to state. Thedrugs are always best given by i.v. injection ofrepeated small doses, or by continuous infusion,until the desired degree of relaxation is obtained.One exception to this rule is that a dose given priorto endotracheal intubation must be large enoughto abolish respiratory movements so that the tubemay be introduced through a completely relaxedlarynx.Neuromuscular blockade is probably bestmaintained during prolonged surgical proceduresby an infusion of the agent after an initial bolusdose. Infusion is commenced when the desiredlevel of block returns after this dose and its rate isadjusted to to maintain this level, with initialadjustments of ± 20%, but adjustments are notmade more frequently than every 5 minutes.Atracurium, vecuronium or mivacurium may begiven in this way and infusion is stopped whenrelaxation is no longer needed. The desired level ofblock is easily established when TOF monitoring isemployed because maintenance of one twitch willprovide good operating conditions; desired blocklevel is more difficult to recognize when TOFmonitoring is unavailable. Most anaesthetists considerthat the dose of relaxant drug used should besuch that if IPPV is temporarily suspended, theanimal is just capable of making feeble respiratoryefforts. Resistance to lung inflation, in the absenceof other obvious causes (e.g. airway obstruction)indicates that forcible respiratory efforts are imminentand a further dose of neuromuscular blockeris required. When an intermittent injection techniqueis used supplementary doses of neuromuscularblockers should not, in general, exceed halfthe initial dose.The maintenance of a light plane of anaesthesiathroughout the operation is of very great importance.Allowing the animal to awaken to consciousnessduring the course of an operationclearly cannot be tolerated but deep central nervousdepression must be avoided or the full benefitderived from the use of neuromuscular blockingdrugs will not be obtained. Once anaesthesia hasbeen induced light anaesthesia may be ensured inone or more of several ways but it is important tonote that if it becomes dangerously light, contractionsof limb or facial muscles will occur eitherspontaneously or in response to surgical stimulation.These movements can always be seen, evenwhen clinically paralysing doses of neuromuscularblockers have been given. The reason for this isunknown, but it is tempting to speculate that the γfibre system nerve endings are more sensitive tothe action of relaxant drugs than are the α fibreendings, for if this is so the neuromuscular blockersmight abolish muscle tonus and produce relaxationwithout entirely preventing contraction of the musclesdue to impulses in the α motor neurones.Theoretically, it is unwise to use drugs of differingactions at the myoneural junction in the sameanimal at any one time. There is some clinical evidenceto support this view yet with a properappreciation of the risks involved and the avoidanceof certain sequences, drugs such as suxamethoniumand pancuronium can be given withsafety to the animal during one operation. Jonesand Gleed (1984) demonstrated that in dogs prioradministration of suxamethonium reduced theduration of action of alcuronium, gallamine andpancuronium. In pigs it is often desirable to producetotal paralysis rapidly with suxamethoniumso as to obtain the best possible conditions for intubationof the trachea and yet to obtain relaxationthroughout the subsequent operation with a nondepolarizingdrug. Provided the effects of suxamethoniumhave worn off (as judged by therespiratory activity) few, if any, harmful effects areseen when the non-depolarizing neuromuscularblocker is given. In dogs, the use of suxamethoniumat the end of a long operation when a nondepolarizingdrug has provided the relaxation upto the last few minutes, seems to involve reductionin the duration of action of the depolarizing agent(Jones & Gleed, 1984a).

174 PRINCIPLES AND PROCEDURESCumulative effects should not be forgotten – if,when bolus administration is being employed, it isnecessary to administer subsequent doses, thequantity of each dose given should not, ingeneral, exceed half the total dose used initially tosecure the desired degree of relaxation. As notedpreviously the aminoglycoside variety of antibioticsmay cause difficulty in antagonism of neuromuscularblock produced by non-depolarizingagents.POSTOPERATIVE COMPLICATIONSOF NEUROMUSCULAR BLOCKINGAGENTSThe most important complication is prolongedapnoea. The best prevention of this complication isthe avoidance of excessive doses. Potentially troublesomedesensitization of the postjunctionalmembrane can be avoided if the anaesthetist doesnot persist with administration of increasinglylarger doses of depolarizing agents in the face ofobvious tachyphylaxis to their blocking effect. Inpostoperative apnoea the animal should be ventilateduntil the cause of the apnoea can be ascertainedand treated. If non-depolarizing agentswere used during the operation and the cause ofapnoea seems to be due to paralysis of the respiratorymuscles, it may be treated by i.v. atropine andan anticholinesterase. There is no antidote to thephase I block of depolarizing drugs and the onlytreatment is IPPV until the return of adequatespontaneous breathing.When an anticholinesterase agent is ineffectivebut the apnoea appears to be due to neuromuscularblock caused by non-depolarizing agents, or isdue to a phase 2 block of the depolarizing agents,the effects of the i.v. administration of potassiumand/or calcium may be tried. In the absence of aurinary output potassium should be given cautiouslyand if possible myocardial activity shouldbe continuously monitored for incipient electrocardiographicevidence of hyperkalaemia (e.g.high spiking T-waves, shortening of the S–T segment).If the administration of potassium is noteffective and there is reason to believe that theplasma level of ionized calcium has been diminished(e.g. after transfusion of large quantities ofcitrated blood), calcium gluconate or calcium chloridesolutions may be given.The commonest cause of prolonged apnoea followingthe use of non-depolarizing agents appearsto be hypothermia. Unless precautions are taken tomaintain the body temperature it falls, especiallyduring laparotomy and thoracotomy. This fall isparticularly great in small animal patients andthere is often difficulty in antagonizing the effectsof non-depolarizing drugs in these animals untilthey are rewarmed. Animals should not be left inthe postoperative period with any residual neuromuscularblock. If dogs are returned to their cageswith any residual curarization, pulmonary atelectasismay develop. Estimation of the tone of themasseter muscle, by gentle traction on themandible, has proved to be a useful test for detectingslight degrees of muscular weakness. If themasseter tone is good there is unlikely to be troublewith respiration.CENTRALLY ACTING MUSCLERELAXANTSMEPHENESINMephenesin is a colourless, odourless, crystallinesolid soluble in ethyl alchohol and propylene glycol.Intravenous injection of a 10% solution leadsto a high incidence of venous thrombosis and alsoto haemolysis which may cause haemoglobinuria,oliguria, uraemia and death. The drug is partlydetoxicated in the liver and partly excretedunchanged in the urine. Mephenesin mixed withpentobarbitone was introduced for canine andfeline anaesthesia but the mixture did not prove tohave any significant advantage over pentobarbitonealone. Mephenesin has many side effects andit is no longer used in anaesthesia.GUAIPHENESINGuaiphenesin (Guaifenesin in North America),formerly known as guaicol glycerine ether, GGE orGG, is a mephenesin-like compound which hasbeen used in Germany for many years (Westhues& Fritsch, 1961) and is now used widely throughoutthe world. Concentrated solutions (over 10%)

RELAXATION OF SKELETAL MUSCLES 175in water or 5% glucose have been associated withhaemolysis, haemoglobinuria and venous thrombosisand although the recently introduced 15%stabilized solutions are said to be be free fromthese effects there is evidence that they causethrombosis. Solutions of 10% in water have minimalhaemolytic effect – they have an osmolality of242mOsm/kg which is closer to the osmolality ofequine plasma than the formerly recommended5% aqueous or dextrose solutions (Grandy &McDonell, 1980) but 10% aqueous solutions giverise to thrombus formation in the equine jugularvein (Herschl et al., 1992). Injection into tissuescauses pain, abscesses and necrosis so that accurateintravenous injection is essential. Venousthrombosis is potentially very serious; it is adelayed complication and may be related to speedof injection since it has been reported to occur withall formulations of guiaphenesin, particularlywhen they were infused under pressure(Schatzmann, 1980). However, the incidence ofvenous thrombosis was greatly reduced when15 % stabilized solutions were administered to2000 horses (Schatzmann, 1988).Cardiovascular depression is dose dependent.In healthy horses heart rate is increased and arterialblood pressure decreased when guaiphenesin isadministered with minimal doses of thiobarbiturates(Heath & Gabel, 1970; Wright et al., 1979).Respiration is also depressed by guaiphenesin,and the PaCO 2 rises (Muir et al., 1977; Muir et al.,1978), an increase in frequency being insufficientto compensate for decreased tidal volume. Itseffects on the cardiopulmonary system have beenstudied in detail by Hubbell et al. (1980). The durationof action in male horses is 1.5 times that inmares but there is apparently no sex difference inthe doses required to produce relaxation (Davis &Wolff, 1970). In contrast to neuromuscular blockingagents significant amounts of guaiphenesincross the placental barrier.Following premedication with acepromazine(0.04mg/kg i.v.) or xylazine (0.6mg/kg i.v.) a mixtureof guaiphenesin and thiobarbiturate given toeffect will produce about 20min of immobilizationin horses. The usual dose requirement is about4 mg/kg of thiobarbiturate and 100 mg/kg ofguaiphenesin. Completing the induction of anaesthesiawith halothane often produces marked arterialhypotension but the pressure recovers slowlyover the next 20 to 30min. Abdominal relaxationobtained with doses of guaiphenesin which do notinterfere with respiratory activity is never as goodas can be produced by the proper use of neuromuscularblocking drugs, but may be useful in situationswhere inhalation anaesthesia cannot beused or where the services of a specialist anaesthetistare not available. For short operations,doses in excess of 50 mg/kg may be associatedwith marked ataxia in the recovery period and thiscan give rise to excitement unless a small dose of asedative such as xylazine is given at the end ofoperation.Guaiphenesin is now used as an ingredient ofthe ‘Triple drip’ for total intravenous anaesthesiain horses with xylazine and ketamine (Greene etal., 1986; Young et al., 1993) or detomidine and ketamine(Taylor & Watkins, 1992).The drug may be used to cast cattle. If these animalsare premedicated with tranquillizers andanalgesics the necessary dose for casting purposesis 4–5g/kg, i.e. about 1l of the 5% solution in anyanimal weighing 500kg. Towards the end, or afterthe completion of this i.v. injection, the animal startsto sway and then falls relaxed. Barbiturates may bemixed with the solution (e.g. 0.25g thiobarbital per50kg body weight) but as the two drugs potentiateeach other most animals fall during the infusion,which is completed in the cast position.Guaiphenesin has been used in other species ofanimal but its administration is rendered difficultby the large volumes of solution which must beinfused. Even in horses and cattle this is a considerabledisadvantage associated with its use, forataxia develops as the solution is run into the veinand care has to be exercised to avoid the type ofinjury to the animal resulting from stumblingwhen the hind legs are crossed.REFERENCESAdams, A.K. and Hall, L.W. (1962) An experimentalstudy of the action of suxamethonium on thecirculatory system. British Journal of Anaesthesia 34:445–450.Adams, A.K. and Hall, L.W. (1962a) The action ofsuxamethonium on the circulatory system.Proceedings of the 1st European Congress of Anaesthesia,Vienna.

176 PRINCIPLES AND PROCEDURESAli, H.H. and Savarese, J.J. (1976) Monitoring ofneuromuscular function Anesthesiology 45: 216–249.Ali, H.H., Utting, J.E. and Gray, T.C. (1970) Stimulusfrequency in the detection of neuromuscular block inhumans. British Journal of Anaesthesia 42: 967–978.Amaki, Y. , Waud, B.E. and Waud, D.R. (1985)Atracurium-receptor kinetics: sample behaviour froma mixture. Anesthesia and Analgesia 64: 777–780.Booth, N.H. and Rankin, A.D. (1953) Studies on thepharmacodynamics of curare in the horse. I. Dosageand physiological activity of d-tubocurarine chloride.American Journal of Veterinary Research 14: 51–59.Borgeat, A. and Kwiatkowski, D. (19997) Spontaneousmovements associate with rocuronium; is pain oninjection the cause? British Journal of Anaesthesia79: 382–383.Bowen, J.M. (1969) Monitoring neuromuscular functionin intact animals. American Journal of VeterinaryResearch 30: 857–859.Bowman, W.C. (1990) Reversal agents. In: Pharmacologyof Neuromuscular Function, 2nd edn. London: Wright,pp 196–202.Brul, S.J., Connelly, N.R., O’Connor, T.Z., and Silverman,D.G. (1991) Effect of tetanus on subsequentneuromuscular monitoring in patients receivingvecuronium. Anesthesiology 74: 64–70.Burns, B.D. and Paton, W.D.M. (1951) depolarization ofthe motor end plate by decamethonium andacetylcholine. Journal of Applied Physiology. 115: 41–73.Cason, B., Baker, D.G.,Hickey, R.F. et al. (1990)Cardiovascular and neuromuscular effects of threesteroidal neuromuscular blocking drugs in dogs(ORG 9616, ORG 9426, ORG 9991). Anesthesia andAnalgesia 70: 382–388.Clutton, R.E. (1992) Combined bolus and infusion ofvecuronium in dogs. Journal of Veterinary Anaesthesia19: 74–77.Cookson, J.C. and Paton, W.D.M. (1969) Mechanisms ofneuromuscular block. Anaesthesia 24: 395–416.Cullen, L.K. and Jones, R.S. (1980) The nature ofsuxamethonium neuromuscular block in the dogassessed by train-of-four stimulation. Research inVeterinary Science. 29: 266–268.Cullen, L.K. and Jones, R.S. (1980a) Recording oftrain-of-four evoked muscle responses from the noseand foreleg in the intact dog. Research in VeterinaryScience 29: 277–280.Cullen, L.K. and Jones, R.S. (1984) Residualnon-depolarizing neuromuscular block assessed bytrain-of-four stimulation in the dog. Research inVeterinary Science 32: 121–123.Cullen, L.K., Jones, R.S. and Snowdon, S.L. (1980)Neuromuscular activity in the intact dog: techniquesfor recording evoked mechanical responses. BritishVeterinary Journal 136: 154–159.Curtis, M.B. and Eicker, S.E. (1991) Pharmacodynamicproperties of succinylcholine in greyhounds.American Journal of Veterinary Research52: 898–902.Davis, L.E. and Wolff, W. A. (1970) Pharmacokineticsand metabolism of glyceryl guaiacolate in ponies.American Journal of Veterinary Research 31: 469–473.Deana, A. and Scuka, N. (1990) Time course ofneostigmine; action on the end plate response.Neurosciences 118: 82–84.Donati, F. (1988) Onset of action of relaxants. CanadianJournal of Anaesthesia 35: S52–S58.Donati, F., Ferguson, A. and Bevan, D.R. (1983) Twitchdepression and train-of-four ratio after antagonism ofpancuronium with edrophonium, neostigmine orpyridostigmine. Anesthesia and Analgesia 62: 314–316.Donati, F., Meistelman, C. and Plaud, B. (1990)Vecuronium neuromuscular blockade at thediaphragm, the orbicularis oculi and the adductorpollicis muscles. Anesthesiology 74: 833–837.Drenck, N.W., Ueda, N., Olsen, N.V. et al. (1989) Manualevaluation of residual curarization using double burststimulation: a comparison with train-of-four.Anesthesiology 70: 578–581.Engbaek, J., Skovgaard, L.T., Friis, B. et al. (1992)Monitoring of the neuromuscular transmission byelectromyography (I). Stability and temperaturedependence of evoked EMG response compared tomechanical twitch recordings in the cat. ActaAnaesthesiologica Scandinavica 36: 495–504.Faye, S. (1988) PhD thesis. Leeds: University of Leeds.Gill, S.S., Donati, F. and Bevan, D.R. (1990) Clinicalevaluation of double-burst stimulation. Anaesthesia 45:543–548.Gleed, R.D. and Jones, R.S. (1982) Observations on theneuromuscular blocking action of gallamine andpancuronium and their reversal by neostigmine.Research in Veterinary Science 32: 324–326.Goat, V.A., Yeung, M.L., Blakeney, C. and Feldman, S.A.(1976) The effect of blood flow upon the activity ofgallamine triethiodide. British Journal of Anaesthesia48: 69–72.Grandy, J.L. and McDonell, W.N. (1980) Evaluation ofconcentrated solutions of guiafenesin for equineanesthesia. Journal of the American Veterinary MedicalAssociation 176: 619–622.Greene, S.A., Thurmaon, J.C., Tranquilli, W.J. andBenson, G.J. (1986) Cardiopulmonary effects ofcontinuous intravenous infusion of guaifenesin,ketamine and xylazine in ponies. American Journal ofVeterinary Research 47: 2364–2367.Hall, L.W. 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RELAXATION OF SKELETAL MUSCLES 177Heckmann, R., Jones, R.S. and Wuersch, W.A. (1977)A method for recording electrical and mechanicalactivity of muscle in the intact dog. Research inVeterinary Science 23: 1–6.Herschl, M.A., Trim, C.M. and Mahaffey, E.A. (1992)Effects of 5% and 10% guaifenesin infusion on equinevascular endothelium. Veterinary Surgery 21: 494–497.Hildebrand, S.V. and Arpin, D. (1988) Neuromuscularand cardiovascular effects of atracurium administeredto healthy horses anesthetized with halothane.American Journal of Veterinary Research 49: 1066–1071.Hildebrand, S.V. and Hill, T. (1989) Effects of atracuriumadministered by continuous intravenous infusion inhalothane-anesthetized horses. American Journal ofVeterinary Research 50: 2124–2126.Hildebrand, S.V. and Hill, T. (1991) Neuromuscularblockade by atracurium in llamas. Veterinary Surgery20: 153–154.Hildebrand, S.V., Hill, T. and Holland, M. 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(1984a) Effects of prioradministration of a non-depolarizing muscle relaxanton the action of suxamethonium in the dog. Researchin Veterinary Science 36: 348–353.Jones, R.S., Heckmann, R. and Wuersch, W. (1978)Observations on the neuromuscular blockingaction of alcuronium in the dog and its reversal byneostigmine. Research in Veterinary Science25: 101–102.Jones, R.S., Hunter, J.M. and Utting, J.E. (1983)Neuromuscular blocking action of atracurium and itsreversal by neostigmine. Research in Veterinary Science34: 173–176.Jones, R.S. and Prentice, D.E. (1976) A technique forinvestigation of the action of drugs on theneuromuscular junction in the intact horse. BritishVeterinary Journal 132: 226–230.Jones, R. S and Richie, H.E. (1965) The effects ofsuxamethonium in a case of myotonia in the horse.British Journal of Anaesthesia 37: 142.Jones, R.S. and Seymour, C.J. (1985) Clinicalobservations on the use of vecuronium as a musclerelaxant in the dog. 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178 PRINCIPLES AND PROCEDURESCollege of Veterinary Anesthesiologists, New Orleans,p 32.Muir, A.W., Houston, J., Green, K.L. et al. (1989) Effects ofa new neuromuscular blocking agent, ORG 9426 inanaesthetized cats and pigs and in isolated nervemusclepreparations. British Journal of Anaesthesia63: 400–410.Muir, W.W., Skarda, R.T. and Milne, D.W. (1977)Evaluation of xylazine and ketamine hydrochloridefor anesthesia American Journal of Veterinary Research38: 195–201.Muir, W.W., Skarda, R.T. and Sheenan, W. (1978)Evaluation of xylazine, guaifenesin and ketaminehydrochloride for restraint in horses. American Journalof Veterinary Research 39: 1274–1278.O’Hara, D.A., Fragen, R.J. and Shanks, C.A. (1986)Reappearance of train-of-four after neuromuscularblockade induced with tubocurarine, vecuronium oratracurium. British Journal of Anaesthesia58: 1296–1299.Payne, J.P. and Hughes, R. (1981) Evaluation ofatracuronium in anaesthetized man. British Journal ofAnaesthesia, 53: 45–54.Pedersen, S.E. and Cohen, J.B. (1990) D-tubocurainebinding sites are located at alpha-gamma and alphadeltasubunit interfaces of the nicotinic acetylcholinereceptor. Proceedings of the National Academy of Sciencesof the USA 87: 2785–2789.Pollard, B.J. and Millar, R.A. (1973) Potentiating anddepressant effects of inhalation anaesthetics on the ratphrenic nerve – diaphragm preparation. British Journalof Anaesthesia 45: 404–415.Riker, W.F. and Wescoe, W.C. (1946) The direct action ofprostigmin on skeletal muscle; its relationship to thecholine esters. Journal of Pharmacology and ExperimentalTherapeutics 88: 58–66.Richards, D.L.S., Clutton, R.E., Boyd, C., Shipley, C. andMcGrath, C.J. (1988) Conditions for trachealintubation in pigs using vecuronium–a comparisonwith succinylcholine. Journal of the Association ofVeterinary Anaesthetists of GB Great Britain and Ireland15: 89–90.Savarese, J.J., Ali, H.H., Basta, S.J. et al. (1988) The clinicalpharmacology of mivacurium (BW B1090U).Anesthesiology 68: 723–732.Schatzmann, U. (1980/81) Advantages anddisadvantages of glycerol guaiacolate (Guaifenesin) inthe equine species. Proceedings of the Association ofVeterinary Anaesthetists of Great Britain and Ireland.9: 153–159.Schatzmann, U. (1988) Discussion on the use of glycerylguiacolate ether (G.G.E.). Journal of the Association ofVeterinary Anaesthetists of Great Britain and Ireland15: 14–16.Silverman, D.G. and Brul, S.J. (1993) The effect of atetanic stimulus on the response to subsequenttetanic stimulation. Anesthesia and Analgesia76: 1284–1287.Stenlake, J.B., Waigh, R.D. and Dewar, G.H. (1981)Biodegradable neuromuscular blocking agentspart 4: atracurium besylate and related polyalkylenedi-esters. European Journal of Medical Chemistry16: 515–524.Stevenson, D.E. (1960) Changes in the bloodelectrolytes of anaesthetized dogs causedby suxamethonium. British Journal of Anaesthesia32: 364–371.Stowe, C.M., Bieter, R.N. and Roepke, M.H. (1958)The relationship between cholinesterase activityand the effects of succinylcholine in the horseand cow. Cornell Veterinarian 48: 241–259.Taylor, P.M. and Watkins, S.B. (1992) Stress responsesduring total intravenous anaesthesia in ponies withdetomidine–guaiphenesin–ketamine. Journal ofVeterinary Anaesthesia 19: 13–17.Trucchi, G., Buracco, P., Mangione, M., Quaranta,G. and Berra, G.P. (1988) Correlation between theduration of action of suxamethonium, serumlevels of pseudocholinesterases and dibucainenumber in the dog. Journal of the Association ofVeterinary Anaesthetists of Great Britain and Ireland15: 96–113.Viby-Mogensen, J., Howard-Hansen, P., Chraemmer-Jorgensen, B. et al. (1981) Posttetanic count (PTC):A method of evaluating an intense nondepolarizingneuromuscular blockade. Anesthesiology55: 458–461.Wachtel, R.E. (1990) Comparison of anticholinesterasesand their effects on acetylcholine-activated ionchannels. Anesthesiology 72: 496–503.Westhues, M. and Fritsch, R. (1961) In: Weaver, A.D.(trans) Animal Anaesthesia, volume 2. Berlin: PaulParey Translated in 1965.Wilson, I.B. (1955) The interaction of tensilon andneostigmine with acetylcholinesterase. ArchivesInternationales de Pharmacodynamie et de Therapie54: 204–213.Wright, M., McGrath, C.J. and Raffe, M. (1979)Indirect blood pressure readings in horses beforeand after induction of general anesthesia withacepromazine, glyceryl guaiacolate andsodium thiamylal. Veterinary AnesthesiaVI: 41–44.Young, L.E., Bartram, D.H., Diamond, M.J. Gregg, A.S.and Jones, R.S. (1993) Clinical evaluation of xylazine,guaifenesin and ketamine for maintenance ofanaesthesia in horses. Equine Veterinary Journal25: 115–119.

Pulmonary gas exchange:8artifical ventilation of the lungsINTRODUCTIONSpecial techniques to ventilate the lungs when therespiratory muscles are paralysed by neuromuscularblocking drugs or rendered inactive by centralnervous depression have evolved gradually over anumber of years. Today, they usually involve endotrachealintubation together with periodic inflationof the lungs and the commonest method usedis known as ‘intermittent positive pressure ventilation’of the lungs or IPPV. It was first employedduring intrathoracic surgery but it is now muchmore widely used in anaesthesia. It is also a routinetechnique in intensive care whenever respiratoryfailure occurs. There are differences betweenspontaneous breathing and IPPV, and IPPV whenthe thoracic cage is opened widely at thoracotomyfrom when it is intact. The anaesthetist mustappreciate what these differences are if IPPV is tobe correctly managed under all circumstances.SPONTANEOUS RESPIRATIONIn a spontaneously breathing animal active contractionof the inspiratory muscles lowers the normallysubatmospheric intrapleural pressure stillfurther by enlarging the relatively rigid thoraciccavity. The decrease in intrapleural pressure lowersthe alveolar pressure (Fig. 8.1) so that a pressuregradient or driving force is set up between theVolume change(%)Pressure(cmH 2 O)10000-5AlveolarpressureTranspulmonary pressureInspirationLung volumePleural pressureExpirationFIG.8.1 Changes in lung volume,pleural andtranspulmonary pressures during normal spontaneousbreathing (diagramatic only).exterior and the alveoli. This overcomes the airwayresistance and air flows into the alveoli untilat the end of inspiration the alveolar pressurebecomes equal to the atmospheric pressure.During expiration the pressure gradient isreversed and air flows out of the alveoli.The transpulmonary pressure is a measure ofthe elastic forces which tend to collapse the lungsand there is no one intrapleural pressure. In theventral parts of the chest it is just sufficient to keepthe lungs expanded. Because of the influence ofgravity acting on the lungs, the intrapleural pressurein the dorsal parts of the chest should bemuch more below atmospheric, but it is not at allcertain how uniform the pressure on the pleural179

180 PRINCIPLES AND PROCEDURESSpontaneous breathingInsp. Exp.A +100–10B +100–10cmH 2 OcmH 2 OIPPVA 200B 100–10cmH 2 OcmH 2 OInsp.electricity, where:ER =RSo that:Resistance =alveolar pressure changeair flowAirway resistance is largely influenced by the lungvolume because the elastic recoil of lung parenchymaexerts traction on the pleural surfaces andwalls of airways (holding them patent) whenthe lungs are inflated above residual volume. As thelungs are further inflated, elastic recoil pressureincreases, thus further dilating the airways anddecreasing resistance to air flow. This relationshipbetween airway resistance and lung volume ishyperbolic in nature, as shown in Fig. 8. 3. Airwayresistance also depends on the nature of airflowthrough the airway. With a clear airway and a lowgas flow rate, intrapulmonary flow is largelylaminar (streamlined) and airway resistance is alsolow, but obstruction or a high flow velocity willgive rise to turbulence and a greatly increasedresistance. Measurement of airway resistance mustbe made when gas is flowing. During IPPV whenthe chest wall is intact, resistance to expansionof the lungs is also offered by the chest wallwhich then contributes to the total respiratoryresistance.Total respiratory resistance (Rr s ) may be estimatedby the application of an oscillating airflowto the airways with measurement of the resultantFIG.8.2 Pressure changes (A) at the mouth end ofendotracheal tube,(B) in the thoracic oesophagus duringspontaneous breathing and IPPV with closed chest(diagramatic only).surface ot the lung really is. The hilar forces, thebuoyancy of the lung in the pleural cavity and thedifferent shapes of the lung and chest wall are allpossible sources of local pressure differences.Thus, it is customary to measure the intraoesophagealpressure as being representative ofthe mean intrapleural pressure (Fig. 8.2)The alveolar pressure changes generate airflowinto and out of the lungs against a resistance in away analagous to that stated by Ohm’s Law forResistance or conductanceABLung volumeAB(2)(1)FIG.8.3 Resistance and volume curves together withlower airways conductance curves (G law ).(1):Resistancecurves;(2):(G law ); A:normal airway B:obstructed airway(Lehane et al.,1980).

ARTIFICIAL VENTILATION OF THE LUNGS 181pressure and airflow changes. A technique wasdeveloped by Lehane et al. (1980) to measure airwayresistance as a function of lung volume duringa vital capacity manoeuvre and so to derivespecific lower airways conductance, s.G law , (conductancebeing the reciprocal of resistance) andthe expiratory reserve volume (ERV). The methodwas modified by Watney for use in anaesthetizedand paralysed horses and dogs (Watney et al., 1987;1988) and it was demonstrated that in poniesxylazine, acepromazine, halothane and enfluraneproduce bronchodilatation and a decrease in ERVwhile isoflurane appears to increase ERV. In dogs,it was concluded that both bronchoconstrictionand changes in lung volume may be responsiblefor changes in airway resistance seen duringhypoxia. During spontaneous breathing changesin resistance may necessitate a great increase inthe work of breathing. The effect of inhalationanaesthetics on total respiratory resistance in conscioushorses was studied by Hall and Young(1992) who showed that halothane appeared tohave no effect while enflurane and isofluraneseemed to increase it.Resistance is not the only factor opposingmovement of air in and out of the chest; a fullanalysis includes the effects of compliance andinertance. Adding the compliance and inertanceforms the reactance and this can be combined withthe resistance in one complex term called the‘impedance’. If the impedance of the respiratorysystem is known then the resistance and reactancecan be determined. A completely non-invasivemethod suggested by Michaelson et al. (1975) has,since the introduction of computers, been usedquite extensively to determine the frequencydependence of resistance in man. Because it doesnot require patient cooperation it is relatively simpleto use in conscious animals as described byYoung and Hall (1989) for horses but it is dificult touse in anaesthetized, intubated animals becausethe impedance of the tube alone is much greaterthan that of a non-intubated animal. Commerciallyavailable apparatus is expensive but, nevertheless,it can provide a useful diagnostic tool for the identificationof horses suffering from chronic obstructivepulmonary disease (COPD) which can poseproblems during anaesthesia with IPPV because ofa sudden increase airway resistance at the end ofResistanceSegmentalbronchi0 5 10 15 20Airway divisionsTerminal bronchiolesFIG.8.4 Contribution of the major and minor airways tototal respiratory resistance.The resistance offered by thesmall airways,each of which has a high resistance,is smallbecause they are in parallel (by analogy with electricalresistance:1/R total = 1/R 1 + 1/R 2 + 1/R 33 ...1/R n ).expiration (Gillespie et al., 1966). This increasedoes not usually present problems during anaesthesiawith spontaneous breathing but may necessitatea prolonged expiratory period during IPPV.Unfortunately, small airways contribute little tothe total lung resistance; although each one has alarge individual resistance, there are large numbersin parallel so that the overall effect is small(Fig. 8.4). This is important because small airwaydisease (which increases local resistance) is notdetected by measurement of total airway resistanceuntil the condition is well advanced.Anaesthetic apparatus may afford resistancethat is considerably higher than that offered by theanimal’s respiratory tract. It is difficult to say atwhat value this apparatus resistance becomesintolerable because a healthy anaesthetized animalseems able to compensate for increases in resistanceto airflow. Anaesthetized human subjectsbreathe at 80 % of control tidal volume against aninspiratory load of 10cm H 2 O (Nunn & Ezi-Ashi,1961). It is unlikely that moderate expiratoryresistance will cause serious problems in spontaneouslybreathing animals provided the PaCO 2remains within acceptable limits. In halothaneanaesthetized horses, Hall and Trim (1975) foundthat 10 and 20cm H 2 O of expiratory resistance didnot affect the PaO 2 but was associated with

182 PRINCIPLES AND PROCEDURESincreases in PaCO 2 of about 1.2mmHg (0.16kPa)per min. However, common sense would seem tosuggest that apparatus resistance should be keptto a minimum. Purchase (1965; 1965a) studied theresistance afforded by four closed breathing systemsused in horses and cattle and in three, all ofwhich had internal bores of 5cm, found it to be ofthe order of 1 cm H 2 O (0.1 kPa) per 100l/min atflow rates of 600 l/min, which he judged to bequite acceptable. He also found that the resistanceof endotracheal tube connectors was relativelyhigh in comparison with that of the remainder ofthe apparatus.During a breathing cycle mean intrathoracicpressure may be above or below atmospheric pressureas a result of apparatus resistance. For example,if the expiratory flow through a piece ofapparatus with a high resistance is great enough toinduce turbulence, whilst the inspiratory rate islower (as it often is in horses) so that during inspirationthe flow is laminar, the mean intrathoracicpressure will be above atmospheric. Conversely, ifthe inspiratory flow rate is greater there may bea subatmospheric mean intrathoracic pressure.Mean intrathoracic pressures above atmosphericmay cause cardiovascular failure in hypovolaemicstates by reducing the effect of the thoraco-abdominalpump for venous return. Large subatmosphericmean intrathoracic pressures may be equally dangerous,perhaps by producing pulmonary oedema,but probably more importantly by reducinglung volume. Trapping of gas in the lungs occursmore readily at low lung volumes and gas trappingproduces widespread airway obstructionwith serious impairment of respiratory function.the PaCO 2 falls below the threshold for stimulatingthe respiratory centre so that spontaneousbreathing movements cease and the anaesthetistcan impose whatever respiratory rhythm isrequired – ‘controlled respiration’.A properly used machine undoubtedly providesthe most efficient means of ventilating thelungs for prolonged periods, but to use a machineproperly or even to squeeze a bag correctly, it isessential to understand the principles underlyingIPPV and to know under what circumstances anypossible harmful effects may arise.Compliance has been defined in many ways butthe simplest definition is that it is the volumechange produced by unit pressure change (δV/δP).Compliance shows hysteresis (Fig.8.5) and it ischanges in surfactant which seem to be responsible;airway resistance and tissue viscosity playonly a small part. Ideally, measurements neededfor the calculation necessary to obtain this valueshould be made when no air is flowing into or outof the lungs (i.e. at the end of inspiration).Compliance measures cannot be compared unlessrelated to a lung volume such as the functionalVolumeDeflateInflateTotallungcapacityIPPV WHEN THE CHEST WALL ISINTACTIPPV is easily applied during anaesthesia byrhythmical compression of the reservoir bag of abreathing circuit. This is most simply achieved bymanual squeezing, but machines have beendesigned and built to relieve the anaesthetist of thebag-squeezing duty. If the bag is squeezed as theanimal breathes in, the tidal volume may be augmented(‘assisted ventilation’). The increased ventilationproduced results in ‘washout’ of CO 2 andPressureResidualvolumeFIG.8.5 Total thoracic compliance curves showinghysteresis.The compliance can be altered by a number offactors: (a) the lung compliance is reduced by lack ofsurfactant (respiratory distress syndrome),reduction ofelastic tissue in the lungs (as in emphysema),and fibrosis orscar tissue;(b) the chest wall compliance is altered byobesity and splinting of the diaphragm by abdominaldisorders.

ARTIFICIAL VENTILATION OF THE LUNGS 183residual capacity (FRC). Unfortunately, measurementof FRC is not a simple procedure and suchmeasurements of compliance as have been madein animals have often omitted this refinement.As commonly measured, compliance has twocomponents and compliance values can be foundfor both the lungs themselves and the thoraciccage but, of course, when the chest wall is notintact the total compliance measured approachesthat of the lungs alone. It might seem that methodsusing high airway pressures to inflate the lungsmight be safe if, when compliance is reduced, it isthe thoracic cage itself which is uncompliantbecause alveoli only rupture when overdistended.On the other hand, decreased compliance of thelungs themselves is apt to be non-uniform, an airwaypressure which produces little ventilation ofsome regions may overdistend and even rupturealveoli in other regions. During anaesthesia compliancemay be altered by assistants resting theirweight on the chest, by the use of retractors and bythe degree of muscle relaxation.Airway resistance has to be overcome to delivergas to the alveoli at inspiration and to expel it duringexpiration. Resistance during anaesthesia isincreased by the resistance of apparatus used, suchas endotracheal tubes. Animals with pulmonarydisease may also have increased airway resistanceso that it is necessary to allow a more prolongedexpiratory period if the lungs are to deflate to FRC.If this is not done lung volume will be greater atthe start of the next inspiration and there will be asteady increase in FRC until the retractive forces ofthe lung, which increase with increase in lung volume,become sufficient to empty the lungs to anew FRC in the time available and the inspiratoryand expiratory tidal volumes become normallyrelated. While conscious, the animal with expiratoryobstruction empties its lungs by active expiratorymovements but, when anaesthetized andparalysed or made otherwise apnoeic, expirationmay become passive and, consequently, of longerduration. The pattern of IPPV used must makeallowance for this, and large tidal volumes shouldbe delivered with long expiratory pauses betweeneach inspiration to allow the chest to return to itsoriginal resting position.The induction of general anaesthesia is usuallyassociated with an increase in resistance due toa decrease in lung volume but this may be counteredto some extent by bronchodilation due tothe agents given, e.g. xylazine, acepromazine,halothane and enflurane.Perhaps the most obvious effect of IPPVwhen the chest is closed is on the circulatorysystem. During spontaneous breathing, by loweringintrathoracic pressure inspiration augmentsthe venous return to the heart; in many animals,as can often be seen on a tracing of continuouslyrecorded blood pressure, there are indicationsthat a increased stroke volume is produced.During IPPV, however, intrathoracic pressure risesduring inspiration, blood is dammed back fromthe thorax, venous return and stroke volumedecrease; blood flows freely into the thoracicvessels during the expiratory period. Fortunately,by causing distension of veins this damming backof blood during inspiration produces a reflexincrease in venous tone which in normal animalsappears to compensate for the changed intrathoracicconditions during the inspiratory periodand restores the venous return towards normality.Obviously the extent to which an increase invenous tone can compensate will depend onthe degree of venomotor integrity (which canbe affected by drugs), the blood volume, themagnitude of the intrathoracic pressure rise andits duration.The magnitude and duration of the increasedpressure within the thorax during the inspiratoryphase of IPPV are, therefore, critical and arereflected in the ‘mean intrathoracic pressure’. Thismean pressure, like the mean arterial blood pressure,is not the simple arithmetical mean betweenthe highest and lowest pressures reached in thesystem and its calculation is not always easy forthe non-mathematician. It is clearly important tokeep this mean pressure as low as possible duringthe respiratory cycle and this can be accomplishedin a variety of ways:1. Short application of positive pressure.The shorter the inspiratory period during IPPVthe lower the mean intrathoracic pressure will befor any given applied pressure. Theoretically, itmight seem that the peak pressure should never bemaintained – expiration should commence as soonas the peak pressure is achieved – or the circulation

184 PRINCIPLES AND PROCEDURESwill suffer. However, the short application of apositive pressure may not result in very gooddistribution of fresh gas within the lungs. In manvery short inspiratory periods have the effect ofincreasing the physiological dead space, whileHall et al. (1968) found a decrease in thephysiological dead space/tidal volume ratio inhorses ventilated with a ventilator which had arelatively long inspiratory phase. A compromiseseems to be necessary here, but exactly what it islikely to be for any one animal of any one speciesremains pure speculation. It is usually taughtthat in small animals (dogs, cats, foals, calves,sheep) the inspiratory time should be 10–1.5s andin adult horses and cattle 2–3s provided the lungsare healthy.2. Rapid gas flow rate.If the necessary tidal volume of gas is to bedelivered to the lungs in a short inspiratory periodit is clear that the flow rate will need to be high.The rate at which gas can flow into the lungs,however, is largely dictated by the resistanceoffered by the apparatus used and the airwayresistance. The airway resistance to the variouslung regions may not be uniform. For example, ableb of mucus may partially obstruct a smallbronchus and greatly increase the resistance to gasflow through it. A high gas flow rate through aneighbouring, unobstructed bronchus may resultin overdistension of the alveoli supplied by it in aninterval of time so short that the alveoli suppliedby the partially obstructed bronchus will not havetime for more than minimal expansion. Theoretically,it would seem that under these circumstancesalveolar rupture might occur, but in practice thiscomplication seems rare.3. Low expiratory resistance.Because any resistance to the airflow createdby the passive phase of IPPV will delay the fallin intrathoracic pressure, it will result in anincrease in mean intrathoracic pressure andpossibly in circulatory embarrassment. However,expiratory resistance can result in more orderlyemptying of alveoli and an increase in FRC withconsequent widening of the airways (Comroe etal., 1962). Thus, at least in some cases (e.g. inanimals with obstructive emphysema) a higherexpiratory resistance may be advantageous to theanimal.4. Subatmospheric pressure during the expiratoryphase.If a subatmospheric pressure is applied to theairway during the expiratory phase of IPPV theinspiratory pressure will be applied from a lowerbaseline. Hence the pressure gradient necessary toproduce the required volume change in the lungscan be achieved with a lower peak pressure. Thismight be expected to help maintain cardiacoutput, but changes in arterial blood pressure andcardiac output are proportional to the durationof the increased airway pressure and not necessarilyto the peak pressures reached. Consequently,merely decreasing the peak airway pressuremay have but little effect if the inspiratory phase islong. Clinical experience in dogs suggests that anybeneficial effects resulting from a subatmosphericexpiratory phase are difficult to appreciate. Inanimals suffering from emphysema where airtrapping occurs, its use will result in furtherimpairment of the expiratory gas flow. Duringthoracotomy its application will cause suchmarked lung collapse that re-expansion may bedifficult.IPPV AFTER OPENING OF THEPLEURAL CAVITYCOLLAPSE OF THE LUNGNormally, distension of the lungs to fill thethoracic cavity is due to the existence of a pressuregradient between the airway and the pleuralcavity. The airway pressure is usually atmosphericand the intrapleural pressure subatmosphericdue to the outward recoil forces of the chest wall,the lymphatic removal of fluid from the pleuralcavity and the limited expansibility of the lungs.This distending force is opposed by what has beentermed the ‘elasticity’ of the lung tissue, althoughthe term ‘elasticity’ is not strictly applicablebecause surface tension in the alveoli contributesin a most important manner to the lung retractiveforce. When the chest is opened and atmosphericpressure allowed to act directly in the pleural cavity,the normal pressure gradient is abolished andthe retractive forces cause the lung to collapse(Fig.8.6).

ARTIFICIAL VENTILATION OF THE LUNGS 185Atmospheric pressureAtmospheric pressureIntact sideOpen sidePendulum airMediastinumParadoxical respirationRelativecross-sectionareas of tracheaRetractiveforcesFIG.8.6 Forces responsible for collapse of the lungfollowing unilateral opening of the chest wall duringspontaneous breathing. The volume of air entering thepleural cavity at each breath will depend on the relativecross-sectional area of the trachea and the defect in thechest wall.The paradox is that during spontaneous breathingfollowing unilateral large openings into the pleuralcavity the lung on the damaged side of thechest becomes smaller on inspiration and larger onexpiration. Normally, when the thorax enlargesdue to activity of the inspiratory muscles itsincreased volume comes to be occupied by airwhich enters via the trachea and blood whichenters the right atrium and thin-walled greatveins. In the presence of a unilateral open pneumothoraxair enters not only into the lungs via thetrachea but also through the chest wall defect intothe pleural cavity. The proportion of air enteringby each route is largely governed by the relativesize of the the chest wall defect to the tracheallumen. When the opening to the hemithorax islarge, or when there is any degree of airwayobstruction, the greater volume of air will enterthrough the hole in the chest wall and the mediastinumwill be pushed towards the intact side ofthe chest. During inspiration pressure in thebronchi on the open side of the chest will begreater than in the trachea because of the additionof the normal retractive forces of the lung to theatmospheric pressure acting on the pleural surfaceof the exposed lung (Fig. 8.7). Thus, on inspirationthe increased volume on the intact side of the chestis occupied by air from the collapsed lung as wellas from the atmosphere. The exposed lung, therefore,becomes smaller. On expiration the lung onthe intact side is discharged partly into the collapsedlung, which becomes larger. In this way ananimal with a unilateral open pneumothoraxbreathing spontaneously shuttles air from onelung to the other. This ‘pendulum air’ produces, ineffect, an increase in respiratory dead space, andthe animal’s respiratory efforts are less effective inproducing overall ventilation. It is not seen afterbilateral opening of the pleural cavity through asternotomy. Applying positive pressure to the airwayduring inspiration abolishes paradoxical respiration.MEDIASTINAL MOVEMENTAtmospheric pressure plusretractive forceFIG.8.7 Effect of unilateral pneumothorax onintrabronchial pressure.In any normal animal the mediastinum is not arigid partition between the two halves of the chest.Veterinary anatomists have made much of thepresence or absence of fenestration in the mediastinumbut in practice this seems unimportantand the behaviour of each half of the chest duringrespiration is always dependent on the conditionsprevailing in the other half. Unilateral pneumothoraxcan occur in all domestic animals and itspresence causes the mediastinum to move towardsthe intact side during inspiration and the oppositeway during expiration. This movement of themediastinum results in obstruction of the thinwalledgreat veins and thus impedes the venousreturn to the heart. However, this impedimentposes little problem and death is usually due tohypoxia rather than circulatory failure. Rigidity of

186 PRINCIPLES AND PROCEDURESthe mediastinum may be encountered in chronicinflammatory pleuritis.EFFECTS ON THE CIRCULATIONIt might be expected that most of the potentiallyharmful effects of IPPV on the circulatory systemwould be absent when the pleura is opened widelybecause an opening in the chest wall should preventcompression of intrathoracic vessels whenpositive pressure is applied to the airway.Nevertheless, in dogs it has been found that thoracotomyreduces the cardiac output to below levelsthat might be expected to result from the applicationof IPPV alone, apparently by causing a furtherreduction in venous return to the heart. It maybe that the airway pressure results in compressionof pulmonary capillaries leading to a diminishedreturn to the left atrium.POSSIBLE HARMFUL EFFECTS OFIPPVThe effects of IPPV on pulmonary ventilation are,of course, in the main clearly beneficial, or the procedurewould not have found such extensive usein the treatment of respiratory failure. Rupture oflung tissue is no more likely to occur during properlyconducted IPPV than during the ordinaryactivities of life. Very high intrapulmonary pressuresdevelop during activities such as coughing,or straining at defaecation or parturition. In dogs,pressures above 100mmHg (13.3kPa) will producefatal air embolism, while during thoracotomypressures above 70 mmHg (9.3 kPa) can producemediastinal emphysema but pressures of thisorder are most unlikely to be encountered duringnormal IPPV where it is seldom possible to createpressure above 60cm H 2 O (6kPa) by compressionof the reservoir bag. Care is needed when ventilatorsare used for, in some, sticking of valves mayexpose the patient’s airway directly to the highpressures at which gases are delivered from theanaesthetic machine to the ventilator. As alreadymentioned, uneven inflation of alveoli is a distinctpossibility during IPPV but the surrounding tissuesseem to provide sufficient support to preventrupture of the relatively overinflated alveoli.Any uneven distribution of gas must have theeffect of disturbing the normal ventilation/perfusionrelationships within the lungs. It appears thatthese are often upset by anaesthesia itself and ifIPPV produces more uneven gas distribution itwill probably fail to affect any improvement in thealveolar–arterial oxygen tension gradient foundduring anaesthesia in spite of any improvement intidal exchange which it may produce. For example,in laterally recumbent horses it is possible thatthe gravitational force gradient from the top to thebottom of the lungs acting on the low pressure pulmonarycirculation may, by reducing the circulationto the upper lung, cause this lung to beoverventilated in relation to its perfusion. Due tothe weight of the horse’s abdominal viscera actingon the lower cone of the diaphragm, IPPV is moresuccessful in inflating the upper than the lowerlung and hence the upper lung receives an evenmore disproportionally large part of the ventilationto the further detriment of its ventilation/perfusionrelationships. Certainly, in the laterallyrecumbent horse IPPV appears to produce very littleimprovement in the alveolar–arterial oxygentension gradient found during general anaesthesia.Other situations in which the normal relationshipsbetween ventilation may be upset occur inall animals where the expansion of one lung orpart of a lung is limited by surgical proceduressuch as ‘packing off’ and retraction of lung lobesduring intrathoracic surgery.IPPV should remove CO 2 from the animal’slungs and it is possible, over a period of time, toremove either too much or too little causing theanimal to suffer from either respiratory alkalosisor acidosis. Respiratory acidosis (hypercapnia) ischaracterized by sympathetic overactivity, cutaneousvasodilatation, a rise in arterial blood pressureand a bounding pulse. Respiratory alkalosis(hypocapnia) may, it has been claimed, lead tocerebral damage from cerebral vasoconstrictionbecause the calibre of the cerebral blood vesselsdepends on the PaCO 2 . However, convincingevidence of cerebral damage due to hypocapniahas yet to be produced. Moreover, although it hasbeen demonstrated that hypocapnia reducescardiac output in horses (Hall et al., 1968), at leastin normovolaemic states no disaster appears toresult.

ARTIFICIAL VENTILATION OF THE LUNGS 187IPPV carried out with a face mask instead ofthrough an endotracheal tube can be harmfulunless care is taken to avoid forcing gases downthe oesophagus into the stomach. This entails carefullimiting of the pressure applied at the mouthand nostrils and observations of the epigastricregion to detect any inflation of the stomach. Aninflated stomach not only hinders intra-abdominalsurgery – if it becomes sufficiently distended withgas, regurgitation of gastric fluid is a distinct possibility.Gas accidentally forced into the stomachshould be removed as soon as possible by passinga stomach tube.MANAGEMENT OF IPPVBefore IPPV can be applied all spontaneousbreathing movements have to be abolished if theanimal is not to ‘fight’ the imposed ventilation.This is usually accomplished by:1. Depressing the respiratory centres byrelative overdose of anaesthetics or agents such asmorphine or fentanyl.2. Paralysis of the respiratory muscles byneuromuscular block.3. Lowering the PCO 2 by hyperventilation.This may be done by forcing a little more gas intothe lungs at the end of a normal inspiration, or byventilating between spontaneous breaths.4. Reflexly inhibiting the respiratory centres byregular rhythmical lung inflation. This inhibitiondoes not depend on changes in blood pH andPaCO 2 . For example, in the cat subjected to IPPV itis known that respiratory neuronal activity usuallysynchronizes with the ventilator cycle within twoto three respiratory cycles; this is too rapid forsignificant changes in the arterial blood gases tooccur. It is believed that if the lungs are slightlyoverdistended at each inspiration afferent impulsesfrom pulmonary receptors inhibit themedullary centres.MANUAL VENTILATIONWhen IPPV is carried out by manual squeezing ofthe reservoir bag (a procedure often known inNorth America as ‘bagging the animal’) thisshould be done gently and rhythmically. Once thedesired degree of lung inflation has been producedthe bag should be released and the lungs allowedto empty freely. The rate of lung ventilation shouldbe faster than the normal respiratory rate of theanimal and the chest wall movement producedshould be more obvious than in normal breathing.During thoracotomy, expansion of the lungbeyond the limits of the wound indicates thatexcessive inflation on the lungs is being produced.Simple observations such as these ensure that ventilationis being carried out in a manner which willresult in no harm to the animal.Because the rhythmical squeezing of a reservoirbag for long periods is both tedious and monotonous,mechanical devices (‘ventilators’) are commonlyused to perform this duty. The use of aventilator frees the anaesthetist to set up intravenousinfusions, keep records, suck out the tracheobronchialtree, and otherwise attend to thewelfare of the patient. Nevertheless, it should benoted that the manual squeezing of a reservoir bagis not to be despised. Observation of the bagbetween compressions shows volume changesdue to the heart beat; the anaesthetist can alter therate, rhythm and character of lung inflation to suitthe convenience of the surgeon at any particularlycritical stage of an operation, and the presence ofrespiratory obstruction is immediately obvious.Theoretically, the effort necessary to produce thedesired degree of lung inflation should give theanaesthetist information about the level of anaesthesiaor degree of relaxation of the respiratorymuscles, more difficult inflation meaning waningrelaxation or lighter anaesthesia. As relaxationwears off it is undoubtedly necessary to exert agreater pressure to maintain the tidal exchange asmay be observed by anyone using suitably calibratedapparatus, but the authors have seldombeen able to appreciate this while actually squeezinga reservoir bag. There may be such a thing asan ‘educated hand’ which recognizes every flickerof the diaphragm, or attempted cough, or waningrelaxation, but it does not seem to be all that easilyacquired.LUNG VENTILATORSA description of every commercially available ventilatoris quite outside the scope of this book and

188 PRINCIPLES AND PROCEDURESthe principles that underlie their operation canonly be outlined. In general, the respiratory cycleof a ventilator can be divided into four parts :1. The inspiratory phase provided by eitherflow generators or pressure generators. With flowgenerators the tidal volume delivered to thepatient is independent of factors outside theventilator – if, for example, the patient’s airwayresistance rises then the inflation pressureincreases. The flow is not necessarily constant andcan be generated by a bellows compressed by acam mechanism or by pneumatic compression ofthe anaesthetic reservoir bag situated in a gas-tightchamber. Pressure generators maintain a constantpressure during the inspiratory phase of therespiratory cycle, often by a weight acting on aconcertina bag. The volume delivered by apressure ventilator will depend on such factors asthe airway resistance (Mushin et al., 1969).2. The changeover from inspiratory to expiratoryphase, i.e. the manner in which the ventilatorcycles, may be (a) time cycled, in which inspirationis terminated after a set time, (b) volume cycled,where inspiration is terminated after a presetvolume has been delivered, or (c) pressure cycled,in which case inspiration ceases as soon as a presetpressure is reached. Not all machines conform tothis classification in that some show mixed cyclingwith hybrid cycling mechanisms. Each type ofapparatus has its own advantages and disadvantagesand discussion of their relative meritsis, again, outside the scope of this book.3. In the expiratory phase a machine may act asa flow generator (e.g. an injector) or a pressuregenerator and the commonest arrangement is toexpose the patient’s airway to atmosphericpressure.4. The changeover from the expiratory to theinspiratory phase may be time cycled or patienttriggered. In the patient triggered ventilator aslight inspiratory effort by the patient triggers thechangeover to the inspiratory phase.Ventilator performance in the presence of changedparameters in the patient is extremely complexand anyone contemplating the use of an unfamiliarventilator is well advised to read any instructionsprovided by the manufacturer and becomethoroughly conversant with its mode of operationbefore attempting to employ it. As a guide, provideda machine meets the following requirements itshould be adequate in most circumstances no matterwhat its mode of operation or mechanism ofcycling may be.Essential characteristicsFor use in cats, dogs, sheep, goats, small calves andsmall pigs, a ventilator needs to provide tidal volumesup to 1000 ml at a cycling rate of from 8 toabout 40 cycles/minute. The duration of the inspiratoryphase should be variable, independent ofthe other settings and range from about 0.5 to 3.0sduration. Whenever possible the expired volumeshould be monitored since due to leaks the ‘strokevolume’ of the ventilator may not represent thetidal volume delivered to the animal.Difficulty is experienced in using many commerciallyavailable ventilators in cats and smalldogs. The problems involve the provision of highrespiratory rates, and low tidal volumes. Adaptationof ventilators designed for adult humans canbe accomplished by employing a controlled leak ora parallel resistance and compliance used in conjunctionwith an Ayre’s T-piece. However, suchsystems are complicated and the ventilatorsdesigned specifically for veterinary purposes offera better solution to the problem (Fig 8.8).Since there is nothing more tiresome than havingto adjust all the controls of a ventilator whenonly one setting needs correction, control of thelength of expiratory period should, like that ofthe inspiratory period, be independent of the othersettings. It should be possible to obtain inspiratory:expiratory ratios of at least 1:3, the expiratoryperiod beginning immediately the desired tidalvolume has been delivered to the lungs. Resistanceto expiration should be low although it may sometimesbe to an animal’s advantage if the expiratoryresistance can be increased (e.g. in emphysematousanimals).A high peak gas flow rate during the inspiratoryphase is always desirable if the lungs are to beinflated in a short inspiratory period. It is comparativelyeasy to adapt a ventilator which gives ahigh peak flow rate to give a lower flow rate but itis impossible to obtain a high peak flow rate from amachine which is not designed to achieve this.

ARTIFICIAL VENTILATION OF THE LUNGS 189AProvided a ventilator satisfies these general criteria,its method of cycling is unimportant. Thereare, however, several points which should betaken into account before buying a machine. First,for safety, it is essential that provision is made for achange to manual squeezing of a reservoir bagshould any mechanical fault develop during thecourse of an operation. Secondly, if electricallydriven, the machine must be electrically safe andexplosion proof. Possibly less important, themachinery should not be noisy and if free standingit should occupy the minimum of floor space. Inpractice, the choice of ventilator is largely one ofpersonal preference, convenience of operation forthe particular circumstances in which it is to beused and the financial resources available.The basic clinical criteria for ventilators for adulthorses, cattle and large pigs are similar to those forthe other animals described above (Fig. 8.9). Auseful ventilator has a tidal volume of between2 and 20 l with a cycling rate of between 4 and15/min and an inspiratory phase of 2 to 3s duration.It should be capable of sustaining pressuresFIG.8.8 A, B One example of a ventilator specially designed for veterinary use is the Hallowell ventilator,which is widelyused in North America and elsewhere.It is electronically controlled,time-cycled and pressure-limited.Interchangeablebellows and housings enable it to deliver accurate tidal volumes of from 20 ml to 3000 ml at safe working pressures of10–60 cm H 2 O with respiratory rates of 6–40 breaths per minute.It can be fitted to all anaesthesia systems without-of-circuit vaporizers (photographs courtesy of Hallowell EMC,63 Eagle Street,Pittsfield,Massachusetts 01201,USA).B

190 PRINCIPLES AND PROCEDURESFIG.8.9 On the Mallard Medical ventilator the controls are easily identified and the setting clearly displayed, making thisventilator very easy to set up.Rachel Model 2800 Large animal anaesthesia ventilator with model 2850 large animalabsorber circuit.1:Microprocessor based ventilator;2:expanded flow rate control for paediatric through to large adultapplication 0–600 litres per minute;3:positive end-expiratory pressure (PEEP) control to enhance oxygenation of thepatient;4:LED display of respiratory values and IE ratio;5:convenient shelves for monitors and accessories;6:mountingwraps on frame and backboard for hoses;7:21 litre ascending bellows with resolution of less than 1 litre;8:surge andnoise suppresser to protect all electronic instruments and provide multiple electrical outlets;9:model 2850 large animalabsorber circuit;10:visible directional valves to observe inhalation and exhalation;11:new advanced design gas balancevalve from human medicine.Allows for visual indication of setting and instant breathing circuit pressure relief;12:ultracapacity soda lime canister for removal of carbon dioxide;13:patient airway pressure gauge;14:vaporizer (not part ofmodel 2800) backboard has holes located for either two Ohmeda or two Drager vaporizers,or a combination;15:oxygenflush,delivers 100% oxygen to absorber circuit; 16:anaesthesia flowmeter (1–10 litres per minute) to vaporizer;Note:not shown is an optional paediatric bellows assembly,providing tidal volumes of 200 ml to 2.20 litres (photographcourtesy of Mallard Medical,Inc.,20268 Skypark Drive,Redding,California 96002,USA).of up to 60 cmH 2 O (6 kPa) in the upper airwayduring inspiration, although it must be noted thatSchatzmann (1988) reported that peak inspiratorypressures above 20cmH 2 O lead to overdistensionof lung tissue in the apical regions of the horse’slungs and to discharge of unidentified fluid out ofthe lungs during recovery from anaesthesia. Theinspiratory: expiratory ratio should be at least 1:2.To achieve sufficiently high gas flows and tidalvolumes special machines were developed for usewith large animals and often constructed to localspecifications. Commercially made ventilatorsfor adult horses and cattle are now available butproper data on their performance is scarce.Ventilator settingsA survey of the literature reveals wide variationsin the recommendations for tidal and minute volumesof respiration when IPPV is used. There are

ARTIFICIAL VENTILATION OF THE LUNGS 191no generally agreed values for the production ofadequate levels of ventilation in horses and evenin dogs, where more studies have been done, publishedfigures range from 20 to 30ml/kg (tidal volume)and from 400 to 600ml/kg (minute volume),so it is clear that numbers such as these can only beregarded as a very rough guide. In horses and cattleit is suggested that a tidal volume of 10ml/kg ata rate of 8 to 12 breaths per minute, with an inspiratory:expiratory time ratio of 1:2 and a peak airwaypressure not exceeding 30 cm H 2 O shouldprovide suitable initial settings for IPPV, althoughthese may need to be modified as anaesthesia proceeds.Ideally, the end tidal concentration of carbondioxide may be monitored continuously and,once the end tidal to arterial tension difference hasbeen derived from blood gas analysis, the ventilationmay be adjusted to yield a normal PaCO 2 ; it isimportant to note, however, that the end tidal toarterial carbon dioxide gradient may change duringthe course of anaesthesia. In practice, facilitiesfor rapid gas and blood analysis are limited byfinancial and other constraints and it is often necessaryto perform IPPV without such assistance.For small animal patients, where non-rebreathingsystems can be employed, it is relatively easyto ensure the maintenance of satisfactory PaCO 2by deliberately hyperventilating at large tidalvolumes with a gas mixture containing 4% CO 2and at least 30% O 2 . Using such a gas mixture inthis way it is only necessary to ensure that largetidal and minute volumes are being imposed andthis can be done from observation of the frequencyof lung inflation and the amplitude of the chestwall excursions.In large animals, where for reasons of economyin the use of gases it is essential to employrebreathing systems, it is much less easy to ensuresatisfactory blood gas levels and, in the absence ofmonitoring facilities, the anaesthetist has to rely onexperience and aim to err, if at all, on the side ofproviding a mild degree of hyperventilation. Ingeneral, it is better to ventilate at slower rates withlarge tidal volumes than to achieve the sameminute volumes by faster rates and smaller tidalvolumes because low tidal volumes predispose tothe lung collapse which necessitated the ‘obligatorysigh’ incorporated into the mechanism ofearlier ventilators.WEANING FROM IPPVIt is important to note that while in most animalsapnoea may be established with the aid of neuromuscularblocking or centrally depressant drugs,in all cases at the end of operation apnoea shouldbe mainly due to reflex inhibition of respirationby the rhythmical slight overinflation of thelungs and, possibly, hypocapnia. Thus, promptresumption of spontaneous breathing usually followsif:1. The rhythm of lung inflation is broken.2. Some accumulation of CO 2 is allowed byeither by slowing the ventilation rate,removing the soda lime canister or, innon-rebreathing systems, by adding moreCO 2 to the inspired gases.Residual neuromuscular block should be counteractedwhere appropriate by the i.v. administrationof anticholinergic and anticholinesterase drugs.This should be done before any CO 2 accumulationis encouraged because anticholinesterases appearless likely to produce cardiac irregularities whenthe PaCO 2 is low. When inhalation anaestheticshave been used the inspired anaesthetic concentrationshould be decreased. Provided only minimalcentral depression by anaesthetic agents is presentanimals will resume spontaneous breathing atvery low PaCO 2 . Dogs have been observed to startbreathing with PaCO 2 as low as 18–20 mmHg(approx. 2.2kPa).In cases where apnoea is established by the useof centrally acting drugs, antagonists such asnaloxone may be given at the end of operation toovercome the respiratory depressant effects, butthe relatively short action of the drugs commonlyused today (e.g. fentanyl) usually makes thisunnecessary.PEEP and CPAPIn many conditions of advanced lung disease theimposition of an expiratory threshold has beenshown to have beneficial effects on the PaO 2 .According to Nunn (1977), use of an expiratoryresistor during IPPV is known as PEEP (positiveend-expiratory pressure) and during spontaneousbreathing as CPAP (continuous positive airwaypressure).

192 PRINCIPLES AND PROCEDURESThe respiratory benefits of an expiratory resistorinclude an overall reduction in airway resistancedue to an increase in FRC, movement of thetidal volume above the airway closing volume, atendency towards re-expansion of any collapsedlung and, possibly, a reduction in total lung water.The net result is that ventilation/perfusion relationshipsare improved. However, these advantagesare, in some circumstances, counterbalancedby circulatory disadvantages due to the inevitablerise in mean intrathoracic pressure. Although thevenous return can be restored by an α adrenergicstimulator such as dobutamine, or by over-transfusion,in clinical practice the situation is morecomplicated.Both disease and drugs have profound effectson the circulatory response to a rise in meanintrathoracic pressure due to PEEP (or CPAP).Certain conditions may aggravate the reduction incardiac output but others actually oppose it and itis in these latter conditions that PEEP or CPAP islikely to be of benefit. In animals with poor lungcompliance much of the applied end-expiratorypressure will be opposed by the excessive pulmonarytransmural pressure, thus minimizing theincrease in intrathoracic pressure. Thus, the stifferthe lungs, the safer is the application of PEEP orCPAP likely to be.To summarize, PEEP and CPAP may confer respiratoryadvantages and circulatory disadvantageswhich interact in a complicated mannerrendering it necessary to make direct measurementsof the relevant physiological functions toensure that overall benefit results.The results of PEEP and CPAP during routineanaesthesia are disappointing. Colgan et al. (1971)showed that PEEP produced no change in thealveolar–arterial gradient in anaesthetized dogs.Hall and Trim (1975) failed to demonstrate anybenefit from CPAP in anaesthetized horses, andbroadly similar results were obtained by Beadle etal. (1975). These results all probably indicate thatanaesthesia produces no reduction in lung compliancein veterinary patients free from pulmonarydisease. There would, therefore, seem to be noindication for the use of PEEP or CPAP in routineanaesthesia in healthy animals. Use of PEEP orCPAP in animals suffering from respiratory diseasedoes not appear to have been documented.HIGH FREQUENCY LUNG VENTILATIONVentilation with tidal volumes of less than theanatomical dead space volume can provide adequategas exchange in the lungs. The means ofachieving this are not immediately obvious.Effective gas exchange in the lungs requires freshgas to be presented to the animal’s alveoli and theremoval of used gas from the alveoli. The amountof gas required per minute to accomplish this isdetermined by the size and metabolic rate of theanimal. Conventional artificial ventilation describedin this chapter uses rates and tidal volumeswithin the physiological range but using smalltidal volumes and higher respiratory frequenciesis associated with lower peak inspiratory airwaypressures and less fluctuation in intrathoracicpressure.The transition from the conducting airways,with no gas exchanging function, to the alveolarsacs where gas exchange takes place, is not sharplydemarcated anatomically. The respiratory bronchiolesare predominently conducting passagesbut do have alveolar sacs opening off them.The alveolar ducts have gas exchanging epitheliumthroughout and in addition conduct gas tothe alveoli. Thus any gas which penetrates tothe respiratory bronchioles by bulk convectionfrom the mouth and nose will take part in gasexchange.Within the lung differing regions have differenttime constants (product of compliance and airwayresistance). Some areas of the lung are fast fillerswith short time constants, whereas other areasare slow fillers with long time constants. Duringearly inspiration the fast filling regions becomefull and during late inspiration are actually emptyinginto the slow fillers. This is known as‘Pendelluft’, and the sum of gas movement withinthe lung is greater than the gas flow down the trachea;there is gas movement between regions ofthe lung without gas movement in the trachea. Itis, therefore, apparent that when small tidalvolumes are delivered at high frequency, a slowfiller could still be filling from a fast filler which atthe same time is providing gas for expiration upthe trachea.Even with high ventilation frequencies freshgas presented to the alveoli has ample time to dif-

ARTIFICIAL VENTILATION OF THE LUNGS 193fuse across the alveolar zone (for this is completewithin 10 ms.) and thus there is an enhancedpotential for molecular diffusion to take a considerablygreater role in the movement of gas acrossthe alveoli.High ventilation frequencyIn the conventional model of ventilation a massof gas under pressure (potential energy) is presentedat the airway opening. This potentialenergy is converted to kinetic energy to allowthe gas to flow down the airway. By the end ofinspiration this kinetic energy has become zero forthe gas is then static and the energy is stored aspotential energy in the distended lungs. The timecourse for this change is determined by the timeconstant for the lung and it is known that 95% ofchange occurs within three time constants. It isobvious that with higher frequencies of ventilationthere will be insufficient time for inspirationto go to completion, i.e. with static gas distendingthe lung alveoli. It therefore follows that withhigher ventilatory frequencies either a reducedtidal volume is delivered to the lung peripheryor a higher peak pressure is required to forcethe gas into the lung periphery within the timeavailable.With high frequencies of ventilation the kineticenergy of the molecules of gas undergoing bulkconvection as ventilation cycles from inspiration toexpiration becomes increasingly important. Asventilation changes from inspiration to expirationthe gas retains its forward kinetic energy and willcontinue to progress peripherally until this kineticenergy is dissipated. This inertia of gas moleculesis not present with conventional IPPV since endinspirationis a static state.The pressure–flow relationships at conventionalbreathing rates are adequately expressed by airwaysresistance but with higher frequenciesairways resistance can no longer be assumed to beconstant and inertia makes an increasing contribution.Thus, at higher frequencies airway impedance,which takes inertia into account, must beused to express pressure–flow relationships. By farthe largest component of impedance to high frequencyventilation lies in the endotracheal tube.This impedance is greatest with a wide bore endotrachealtube and high gas flow rates (large tidalvolumes at high frequency).At normal breathing rates gas distributionwithin the lung is determined by regional compliance.However, with higher respiratory ratesairway resistance and gas inertia have an increasingeffect on the distribution of ventilation.Potentially, this will result in a change of ventilationfrom areas of high compliance to areas oflow impedance. Since there is no evidence tosuggest that regional lung perfusion is altered,high frequency ventilation must, therefore, resultin changes in lung ventilation–perfusion ratios.Another aspect of high frequency ventilation isthat it involves less time for the bulk convection ofgas during inspiration and expiration so that thegas path length becomes increasingly important.Thus, in animals such as horses with long tracheas,pressures at the airway distend the major conductingpassages, then the nearby fast filling lung unitsand finally the peripheral slow filling units. With aprogressive shortening of the inspiratory time asituation will arise when there is insufficient timefor the tidal volume to get beyond the major conductingpassages which will then act in a wayanalagous to that of an electrical capacitor. Theimplication of this is that pressure at the airwayopening is not transmitted to the lung peripheryand hence the pleural space. However, the reversewill also occure in that there will not be enoughtime for the intra-alveolar pressure to emptythe alveoli so that there will be a continuouspositive pressure in the peripheral lung units.This should, in theory, be beneficial in elderly animalsor in those with a reduced FRC since smallairway closure is most likely to occur in thesepatients.Methods for achieving high frequencyventilation of the lungsConventional ventilators deliver a volume of gasduring inspiration by occlusion of a relativelywide bore orifice through which expiration takesplace and the device to occlude the expiratoryorifice must function rapidly. The more rapidlythis device is made to operate the more likely valvebounce is to occur so that conventional ventilatorscannot, in general, operate at frequencies above

194 PRINCIPLES AND PROCEDURES2 Hz. Because of this limitation high frequencyventilation is normally provided by either highfrequency jet ventilation (HFJV) or high frequencyoscillation (HFO).High frequency jet ventilatorsThese ventilators allow a high pressure gas sourceto flow into the airway during part of the respiratorycycle, usually 20–35% of the cycle time,through a narrow diameter tube usually at tracheallevel. They require no expiratory seal andhence the airway is open to atmospheric pressurethroughout the cycle. This potentially results inentrainment of an unknown quantity of ambientgas and thus the volume and composition ofthe tidal volume is unknown. The system has theinherent safety advantage that the animal can takea spontaneous breath at any time during the respiratorycycle.High frequency oscillatorsOscillator type ventilators tend to be used forhigher frequencies (6 to 40Hz). A piston driven bya motor or an electronically driven diaphragm atthe airway opening generates a to-and-fro motionof gas within the airway. The tidal volume resultsfrom displacement of the piston or diaphragm anda subatmospheric airway pressure is generatedduring the expiratory half of the respiratory cycle.Fresh gas is fed in at the airway opening and a lowpassfilter exhaust port allows gas to exit the system.The low-pass filter offers a high impedance tohigh frequencies which are thus able to direct thetidal volume down the airway, which has a lowerimpedance, rather than be lost through the exhaustport.Carbon dioxide elimination and oxygendeliveryOn theoretical grounds it might be expected thatwith a constant tidal volume there should be alinear relationship between CO 2 removal and ventilatoryfrequency until such a time as the durationof inspiration is insufficent to permit the gas topenetrate the conducting airways to the gasexchanging regions of the lung. In practice thisseems to be the case and there is a critical frequencyat which CO 2 elimination reaches a peak.Above this frequency CO 2 elimination becomes afunction of tidal volume and independent of ventilatoryfrequency. The critical frequency is dependenton the anatomy of the lung and is certainlyhigher in dogs than in horses.One of the original hopes for high frequencyventilation was that the change from compliance/airwayresistance distribution of ventilationto one determined by airway resistance/gas inertiawould result in improved distribution of gaswithin the lung and an improvement in ventilation.However, it is now generally accepted that, atequivalent tidal volumes, neither HFJV nor HFOproduce improvement in PaO 2 , over that whichcan be attained by conventional ventilation techniques.Reports to date of high frequency lungventilation in veterinary patients (Wilson et al.,1985; Dunlop et al., 1985; Dodman et al, 1985) arenot encouraging.LUNG VENTILATION IN INTENSIVE CARELong term IPPV over several days may be necessaryafter cardiopulmonary resuscitation, prolongedrecovery from anaesthesia, or in animalspresently unable to maintain an adequate PaO 2when breathing 60% O 2 but which are expected torecover after appropriate treatment. IPPV is usuallycarried out with an air/oxygen mixture, theinspired O 2 concentration being adjusted to yieldan arterial O 2 saturation of over 90% as shown bypulse oximetry.Animals which are restless may require sedationor even light general anaesthesia for toleranceof the endotracheal tube (which is obligatory forthe performance of IPPV). In dogs, cats and smallruminants an oral endotracheal tube is usual but infoals it is customary to employ a nasotracheal tube.Humidification of the inspired gases is necessary ifhigh gas flows are employed but at low flows sufficientwater vapour appears to condense on theinside of a rebreathing circuit to provide the waternecessary for humidification. With high gas flowsa disposable condenser-humidifier between theendotracheal tube and and delivery circuit is aconvenient method of ensuring proper humidificationof the inspired gas.

ARTIFICIAL VENTILATION OF THE LUNGS 195REFERENCESBeadle, R.E., Robinson, N.E. and Sorensen, P.R.(1975) Cardiopulmonary effects of positiveend-expiratory pressure in anesthetized horses.American Journal of Veterinary Research.36: 1435– 1438.Colgan, F.J., Barrow, R.E and Fanning, G. (1971)Constant positive pressure breathing andcardiorespiratory function. Anesthesiology34: 145–151.Comroe, J.H., Forster, R.E., Dubois, A.B., Briscoe, W.A.and Carlsen, E. (1962) The Lung, 2nd edn. Chicago:Year Book Medical.Dodman, N.H., Lehr, J.L. and Spaulding, G.L.(1985) High frequency ventilation in largeanimals. Proceedings of the 2nd InternationalCongress of Veterinary Anaesthesia, Sacramento,pp 186–187.Dunlop, C., Steffey, E.P., Daunt, D., Kock, N. andHodgson, D. (1985) Experiences with high frequencyjet ventilation in conscious horses. Proceedings of the2nd International Congress of Veterinary Anaesthesia,Sacramento, pp 190–191.Gillespie, J.R., Tyler, W.S. and Eberly, V.E.( 1966) Pulmonary ventilation and resistancein emphysematous and control horses. Journalof Applied Physiology. 21: 416–422.Hall, L.W., Gillespie, J.R. and Tyler, W.S. (1968)Alveolar–arterial oxygen tension differences inanaesthetized horses. British Journal of Anaesthesia40: 560–568.Hall, L. W. and Trim, C.M. (1975) Positiveend-expiratory pressure in anaesthetizedspontaneously breathing horses. British Journal ofAnaesthesia 47: 819–824.Hall, L.W. and Young, S.S. (1992) Effect of inhalationanaesthetics on total respiratory resistance inconscious ponies. Journal of Veterinary Pharmacologyand Therapeutics 15: 174–179.Lehane, J.R. Jordan, C. and Jones, J.G. (1980) Influenceof halothane and enflurane on respiratory airflowresistance and specific conductance in anaesthetizedman. British Journal of Anaesthesia 52: 773–781.Michaelson, E.D., Grassman, E.D. and Peters, W.R.(1975) Pulmonary mechanics by spectral analysis offorced random noise. Journal of Clinical Investigation56: 1210–1230.Mushin, W.W., Rendell-Baker, L., Thompson, P. andMapleson, W.W. (1969) Automatic Ventilation of theLungs. Oxford: Blackwell Scientific.Nunn, J.F. (1977) Applied Respiratory Physiology. London:Butterworths, p 128.Nunn, J.F. and Azi-Ashi, T.I. (1961) Respiratory effects ofresistance to breathing in anaesthetized man.Anesthesiology 22: 174–175.Purchase I.F.H. (1965) Function tests on four largeanimal anaesthetic circuits. Veterinary Record77: 913–919.Purchase I.F.H. (1965a) Some respiratory parametersin horses and cattle. Veterinary Record 77: 859–860.Schatzmann, U. (1988) Artificial ventilation in thehorse. Advances in Veterinary Anaesthesia: Proceedings ofthe 3rd International Congress of Veterinary Anaesthesia,Brisbane, pp 29–34.Watney, G.C.G., Jordan, C. and Hall, L.W. (1987)Effect of halothane, enflurane and isoflurane onbronchomotor tone in anaesthetized ponies. BritishJournal of Anaesthesia 59: 1022–1026.Watney, G.C.G., Jordan, C., Hall, L.W. and Nolan, A.M.(1988) Effects of xylazine and acepromazine onbronchomotor tone of anaesthetized ponies. EquineVeterinary Journal. 20: 185–188.Wilson, D.V., Soma, L.R. and Klein, L.V. (1985) Highfrequency positive pressure ventilation in the equine.Proceedings of the 2nd International Congress ofVeterinary Anaesthesia, Sacramento, pp 188–189.Young, S.S. and Hall, L.W. (1989) A rapid, non-invasivemethod for measuring total respiratory impedance inthe horse. Equine Veterinary Journal 21: 99–105.

Apparatus for the9administration of anaestheticsADMINISTRATION OF INTRAVENOUSAGENTSFor agents which are intended to reach the centralnervous system and produce narcosis or anaesthesiathe intravenous route is obviously more directthan one through the respiratory tract. But it mustalways be borne in mind that unlike the respiratorypathway the intravenous one does not providean exit as well as an entrance and, for thisreason, apparatus used for the administration ofintravenous agents must be designed to allow accuratecontrol of the amount given, for once injected itcannot be recovered from the animal’s body.Although any superficial vein may be used, thechoice of vein does not influence the apparatuswhich may be employed and detailed descriptionsof the techniques of venepuncture will be found inthe chapters concerned with anaesthesia of thevarious species of animal.SYRINGES, NEEDLES AND CATHETERSThe largest syringe which can be handled convenientlyis one of 50 to 60 ml capacity and for easypercutaneous venepuncture all those of greatercapacity than 2 ml should have eccentricallyplaced nozzles. All-glass syringes are easy to sterilizebut have plungers which tend to stick duringinjection and, although theoretically the best inwhich to collect samples of blood for blood gasanalysis (see Chapter 2) even for this purpose theyhave been replaced by the disposable plastic varietywhen no delay between collection of the sampleand its analysis is anticipated.Needles must be sharp and their points should,preferably, have a short bevel to reduce the risk oftransfixing the vein: good quality disposable needlesare always sharp. In small animals insertion ofa needle or catheter through the skin may be renderedpainless by the prior application of a localanalgesic cream to the skin after suitable hair clipping.EMLA cream, a eutectic mixture of lignocainebase 2.5% with prilocaine base 2.5% appliedunder an occlusive dressing for 60 min prior tovenepuncture, has been reported to be effective,but amethocaine 4% gel also applied under anocclusive dressing needs only 30 min to producesimilar analgesia. In horses and cattle it is customaryto desensitize the skin by the intradermal ors.c. injection of a small bleb of 2% lignocainehydrochloride through a 25 gauge needle or via anair powered intradermal injector, prior to theinsertion of a large bore catheter.The administration of intermittent small dosesof a drug, or its constant infusion, normallyrequires that a catheter be kept in the vein and freefrom blood clot. Methods in which a needle is leftin the vein and an attached, loaded, syringestrapped to the patient are rarely satisfactorybecause movement between the skin and the vein,or of the patient, results in displacement of the needle.Unless this mishap is noticed it may lead to197

198 PRINCIPLES AND PROCEDURESFIG.9.1 Disposable plastic ‘catheter over-needle’.Manypatterns are available.haematoma formation and/or the extravascularinjection of drugs, some of which (e.g. guaiphenesin,thiopentone) may be highly irritant to thesurrounding tissues.Where anaesthesia is to be supervised bynursing staff or a technician it is particularlyimportant to ensure there is a secure open venousline before commencing surgery. Venous access isusually ensured with a plastic catheter (Fig. 9.1).Proprietary catheters for this purpose are suppliedsterile: they consist of a nylon, polythene or tefloncatheter around a hollow metal needle or trocar,the point of which projects just beyond the taperedend of the catheter. The catheter is inserted into thevein with the trocar needle in position and the needleis withdrawn when blood flows from its proximalend or is seen to enter the catheter hub. Theneedle hub is then held firmly while the catheter isadvanced well up the vein and secured in positionwith adhesive tape or a stitch. Because the catheteris blunt ended it does not transfix the vein and along length can be threaded into the vein. Once thecatheter is in position the needle is completelywithdrawn. To prevent unwelcome spilling ofblood from a peripheral vein it is customary, assoon as the catheter has been sited, to occlude thevein by exerting digital pressure over the cathetertip (usually easily located by palpation) until anobturator or tap is affixed or an infusion connected.An attempt to insert one of these cathetersdirectly through the skin may result in the tip ofthe catheter opening out into a bell-mouth shapewhich is almost impossible to introduce into thevein, so they should be inserted through a smallskin incision. Often, a small skin incision for thispurpose can be made with the cutting edge of aneedle. Should venepuncture be found to beunsuccessful, even if the needle has only been partiallywithdrawn from the catheter, it must not bereinserted unless the catheter is completelyremoved from the tissues because it may penetratethe side wall of the catheter and sheer off the distalportion.More than than 25 different patterns of ‘catheterover needle’ are commercially available in theUnited Kingdom alone. There is some variation ontheir general shape and some have small handlesto aid insertion. Most have plastic needle hubsthrough which which blood can be seen when theneedle enters the vein. Three important factorsgovern the choice of catheter. First, it should be nolonger than strictly necessary. The length of mostcatheters (up to 7cm) is always adequate and thereis no need for the larger diameters to be longer.However, exceptions to this rule may be made incircumstances when the need to ensure that thecatheter remains in the vein at all costs (e.g. whenadministering guaiphenesin to a horse) outweighthe effect of the increased length on resistance toflow. The second important feature is the wallthickness. It is the external diameter which largelydetermines the size chosen in any given situationand catheters with thinner walls obviously permitmore rapid infusions. The third factor is that theexternal shape should be as smooth as possible, forcatheters with smooth contours are the easiest tointroduce.Longer catheters are available for special purposessuch as measurement of the central venouspressure (see Chapter 2). Although it is possible toobtain some of the catheters described above up to5.25 inches (13.3cm) in length (which may be adequatefor central venous pressure measurement incats and small dogs), the longer catheters are generallynot provided with introducing needles.Whenever possible, they are introduced into thevein through a previously placed large borecatheter. Some long catheters (e.g. Abbotts DrumReel) are supplied with an additional short, widerbore catheter of the ‘over needle pattern’ that isintroduced into the vein so that the longer one canbe threaded through it.Veins (and arteries) can be catheterized over aguidewire. Originally described as the ‘Seldinger’

ANAESTHETIC ADMINISTRATION 199DilatorDilatorNeedleSheathVeinVeinVeinGuide wireGuide wireLong softcatheterFIG.9.2 Technique for the insertion of a long,softcatheter (e.g.Swan–Ganz) into a vein by the modifiedSeldinger technique.The vein is first penetrated with aneedle through which the guide wire is threaded as soonas the needle is placed in the vein.After withdrawing theneedle,a sheathed vein dilator is introduced over theguide wire and the dilator and guide wire are removed toleave the dilator sheath patent for the introduction of thecatheter.technique for arterial cannulation, this method isnow used to introduce catheters which are too flexible,blunt ended or too large to be inserted directlypercutaneously. It is commonly used for arterialcatheters, right atrial feeding catheters, cathetersfor injecting radiological contrast media, cardiacpacing catheters and pulmonary artery flowdirected catheters, but it may be used for any intravenouscatheter placement. A relatively small needleor catheter is introduced into the vessel, aguidewire is inserted through it and the catheter iswithdrawn. A large bore vein dilator is threadedover the guidewire. Most vein dilators are fragileand a scalpel incision must be made to clear a trackto the vessel. Dilators usually consist of an innersection and a sheath; the inner section is removedwith the guidewire. The catheter proper is insertedthrough the vein dilator sheath (Fig. 9.2). There areseveral designs of guidewire; most have flexibletips followed by a stiffer section. The tip may bepreformed into a J-shape to facilitate its passagethrough angles in the vessels. Some catheters (e.g.radiographic catheters) are stiff enough to bethreaded over the guidewire and passed intothe vessel but softer catheters need to be passedthrough the vein dilator. For asepsis it is saferto ‘gown-up’ completely and towel up a largedisinfected area of skin to avoid contamination ofa very expensive catheter which may not be resterilizable.The number of proprietary catheters of variouslengths now available is bewilderingly large andchoice is difficult. Because the wrong choice ismade intravenous infusions which appear to runsmoothly when originally set up with electrolytesolutions may prove infuriatingly slow whenblood or a colloid solution has to be given. Sucha disadvantage may cost an animal’s life. Considerationof some of the factors influencing the flowmakes the choice of catheter more rational and lessdependent on the information given on the packetby the manufacturers of any particular product.The flow through a tube is proportional to thedriving pressure, which is equal to the pressuredifference between the two ends of the tube, multipliedby a constant, π/8. Flow is also inversely proportionalto the viscosity of the fluid, since themore viscous it is the harder it will be to force itthrough the tube. The final factor governing theflow is the internal diameter of the tube, flowbeing directly proportional to the fourth power ofthe radius, and inversely proportional to thelength of the bore. Thus, for maximum flow of anygiven fluid at any given pressure, the tube shouldbe short, and the diameter large. It must be notedthat a small change in diameter has a great effecton flow velocity.At very high flow rates it may be found that theresistance to flow is disproportionately high. Thereis a critical flow velocity at which flow changesfrom streamline to turbulent. During turbulencethe driving pressure is largely used up in creatingthe kinetic energy of the turbulent eddies. Theflow no longer depends on the viscosity of thefluid but on its density. However, the critical velocityat which turbulence occurs depends mainly onthe viscosity and density of the fluid as well as theradius of the bore of the tube through which it is

200 PRINCIPLES AND PROCEDURESFIG.9.3 ‘Butterfly’ or ‘small vein set’ or ‘infant scalp veinset’.Many types are available but all have lengths of plastictubing attached and most have winged needles to aidinsertion and subsequent fixation to the patient.flowing. In an intravenous infusion system thecritical velocity is likely to be exceeded at veryhigh flow rates and also at local points in theapparatus at which, because of sudden change ininternal configuration, the velocity of flow momentarilyrises. Thus, at points at which the internaldiameter changes suddenly, turbulence will occur.The viscosity of blood is considerably greaterthan that of water, mainly because of the presenceof erythrocytes. It increases with the haematocritand above about 60% packed cell volume bloodhardly behaves as a fluid. Viscosity is also increasedby a drop in temperature, and the viscosityof blood at 0 °C is about 2.5 times as great as at37°C. Blood warming coils are, therefore, justifiedon grounds of increasing the speed of transfusionas well as of preventing the development ofhypothermia in the recipient.An alternative to a catheter for very small veinsis a needle attached to a hub by a length of plastictubing. There are at least nine types of ‘small vein’needles currently available (Fig. 9.3). Some havewinged handles to aid insertion and subsquent fixationto the patient. Flow performance of most ofthe ‘small vein sets’ (often called ‘scalp vein sets’or ‘butterflies’) is surprisingly poor, and it is usuallybest to choose one with the shortest length oftubing attached.INFUSION APPARATUSWhere, as in larger farm animals and horses, largevolume infusions are to be given rapidly, simpleapparatus may be used. However, if a fairly accuratecontrol of flow rate is needed, or the infusionis to be given slowly as may be necessary in smallanimal patients or when potent drugs are to beadministered, a system giving a greater degree ofcontrol is essential. Proprietary disposable plastic‘giving sets’ or ‘administration sets’ are convenientfor these purposes and can be obtained in a varietyof patterns.Essentially, a ‘giving set’ consists of an outlettube which may or may not incorporate a filterdepending on whether the set is for blood andblood products or crystalloids alone, a drip chamberand a long length of plastic delivery tubingwhich can be occluded by some form of adjustableclamp. If it is intended for use with bottles of fluidan air inlet with a filter is incorporated. All plasticsets include a short piece of rubber tubing towardsthe needle mount end of the delivery tube, or a rubbercapped short side arm so that injections can bemade through a fine bore needle whilst the tubingis pinched between the finger and thumb on thedrip chamber side of the injection site to preventthe pressure damming back fluid in the drip chamber.The flow rate is controlled by means of theclamp and can be estimated from number of dropswhich pass through the drip chamber in oneminute. For example, with most sets 40 drops/minute means the administration of approximately500 ml in 4 hours. Much more accurate control ofinfusion rate can be obtained by the use of a driprate controller between the fluid container and thepatient. These are electronic devices which monitorthe drip chamber and, by changing the effectivecross-section area of a section of the standardadministration set tubing, maintain a constantinfusion rate. The automatic control eliminates theneed for frequent adjustment of the drip rate. However,drip rate controllers are expensive and cannotcompensate for variations in drip size so that theactual delivery rate depends on the drop size.Drip rate pumps are similar in cost and appearanceto drop rate controllers and most operate satisfactorilywith standard administration sets. Theygenerate a pressure by peristaltic fingers or rollersacting on deformable tubing to give a constantinfusion rate.Volumetric pumps are designed to avoid problemsassociated with variations in drop size. Very

ANAESTHETIC ADMINISTRATION 201FIG.9.5 Syringe driver.Many types of electrically drivensyringe drivers are available.Some must be used with onespecified size of syringe,others can be used with a varietyof syringes.FIG.9.4 Volumetric or constant infusion pump.Typessuch as this drive a disposable piston pump and the needto refill the barrel of the pump means that the infusion rateis not actually constant.They will,however,maintain areliable infusion rate.Most have devices which warn of thepresence of air in the infusion line or occlusion of the line.good volumetric accuracy is obtained with either areciprocating piston type pump or by peristalticpumping on an accurately made tube which formspart of the administration set. With the piston typepump (Fig. 9.4) no fluid is delivered to the patientduring the refilling stage of the cycle so that at lowflow rates significant fluctuations in delivery rateoccur. The need for a dedicated infusion set addsto the cost of each infusion and the volume of fluidneeded to prime these sets can also be in the regionof 20ml which may give rise to significant wastageof expensive solutions. These pumps are, however,particularly valuable for longer procedures wherethe solution can be withdrawn from a large containersuch as a 3l plastic bag.Electrically driven syringe drivers (Fig. 9.5)overcome many of the problems associated withthe administration of relatively small volumes offluid (e.g. to cats or for the continuous administrationof small volumes of drug solutions duringanaesthesia). They are usually calibrated for a particulartype and size of syringe. The delivery ratecontrol alters the rate of plunger travel and hencethe cross-sectional area of the barrel is critical inensuring that the delivery rate is correct. Thesyringe can be filled from a large container of fluidand connected to the intravenous catheter with asimple administration extension set so that primingvolume is minimal. Syringe drivers are generallyless expensive than volumetric pumps or driprate pumps or controllers as well as being moreportable. Further developments include the use ofprogrammed microprocessor control with an ability(if the pharmacokinetics of the infused substanceare known) to deliver a changing infusionrate such that a steady state of blood concentrationscan be achieved and maintained.Most infusion pumps monitor line pressure bydetecting changes in the motor current needed fordriving and to avoid frequent false alarms the pressureat which an occlusion is indicated is usuallyset well above the anticipated line pressure. Thismeans that occlusion alarms on infusion pumpshave little value in indicating that the fluid is beinginjected into the tissues rather than into a vein.With low flow rates, the time required for a significantincrease in interstitial, and subsequently linepressure, will be long and substantial amounts offluid may be injected before any warning is given.

202 PRINCIPLES AND PROCEDURESPharmaceutical companies now provide intravenousfluids in plastic disposable bag containersand some provide bags with an integral giving set.Because such bags are collapsible, no air inlet isnecessary, air embolism cannot occur and infusionscan be left running unattended, which maybe an advantage for veterinary use. When bottlesof fluid are used, there is a possibility of airembolism should the bottle empty unobserved, asair has to enter the bottle before fluid can leave.When fluids are administered under the influenceof gravity the speed of infusion dependsmore on the bore of the needle or catheter than onthe pressure applied (i.e. the height above the needleor catheter at which the container is held).Doubling the diameter of the needle or cathetergives a 16-fold increase in the rate of flow, whereasa four-fold increase in the pressure is required todouble the rate. However, in the case of the ‘fluttervalve’ apparatus traditional and formerly so popularin veterinary practice, the vertical distancebetween the needle and the air inlet opening determinesthe rate at which air enters the system;increasing this distance increases the rate of airentry and hence the speed of infusion. The ‘fluttervalve’ is unreliable and there is little justificationfor its continued use in veterinary anaestheticpractice except, perhaps, when short duration fastinfusion needs to be given.In circumstances where the maximum size ofthe needle or catheter is limited, the maximum rateof flow of fluid can be increased by pressurizingthe system. Where bottles are in use, they can bepressurized by pumping air under pressurethrough the air inlet. This procedure carries a highrisk of producing air embolism if the supply offluid runs out, so it should be used with cautionand the infusion should never be left unattended.Pressure can be applied to plastic bags of fluid byplacing them in a second bag or container pressurizedby pumping in air; there is then no danger ofair embolism.ADMINISTRATION OF INHALATIONAGENTSThe administration of an inhalation anaestheticrequires:1. A source of oxygen (which may be air)2. A vaporizer or a source of anaesthetic gas3. A ‘patient’ or ‘breathing’ system.In its simplest form modern anaesthetic apparatusconsists of an oxygen cylinder, with pressuregauge, pressure regulator and flowmeter, deliveringoxygen to a suitable patient breathing system.A vaporizer for an inhalation anaesthetic agentmay be included inside or outside the patientbreathing system.DELIVERY AND REGULATION OFANAESTHETIC GASESOxygen cylinders (‘tanks’ in North America)For medical use oxygen is obtained compressed athigh pressure (138 atmospheres or 2000 lb/in 2 )into metal cylinders or as liquid oxygen in specialcontainers. For veterinary purposes cylinders areusually used. In the United Kingdom they arecolour coded black with a white top but in othercountries there is no adherence to what wasintended to be a universal code. In the USA theyare coloured all green and in Canada all white.When delivered, all cylinders have a plastic sealover their outlet to exclude dust and this sealshould be removed only immediately before use.There are two types of cylinder outlet. Some cylindersfit into a yoke over pins which are indexed fordifferent gases so as to make it impossible to attachan incorrect cylinder. A small washer termed a‘Bodcock seal’ is needed around the inlet on theyoke of these pin-indexed fittings. Larger cylindersutilize ‘bull-nose’ fittings which screw intoplace and require no sealing washer.Pressure gaugeIt is essential for the anaesthetist to know thatthere is an adequate supply of oxygen in thecylinder so when in use they are coupled to apressure gauge to register the pressure insideand, therefore, the quantity of oxygen available.Pressure gauges are most commonly of theBourdon type (see Fig. 9.6), consisting of ametal tube, the end of which is attached to apointer. The application of pressure to the inside ofthe tube causes it to straighten and moves thepointer over a scale.

ANAESTHETIC ADMINISTRATION 203shut off by the flowmeter control is very muchreduced.The regulators in common use in anaesthesia usuallyreduce the pressure at which oxygen is deliveredto below 200 lb/in 2 (13.8 atm) and manymodern anaesthetic machines incorporate thevalve into the block featuring the cylinder pinindex so that on superficial inspection of themachine they may be difficult to identify. Furtherdetails of these regulators can be obtained fromsuch texts as Ward’s Anaesthetic Equipment byMoyle and Davey (4th edn. (1997) W. B. Saunders)and will not be considered here.FlowmetersToday most of the flowmeters used in anaesthesiain the UK are known as ‘rotameters’ (Fig. 9.7).They make use of the interdependence of flowrate, size of an orifice and the pressure differenceon either side of the orifice. The rotameter consistsFIG.9.6 Bourdon gauge.These are used for measuringgas pressure and,placed before an orifice,for gas flowmeasurement.Reducing valves or regulatorsA pressure reducing valve at the cylinder outlet oron a pipeline supply is necessary for three reasons:1. For cylinder supplies, once the flow has beenset for any particular level, frequent readjustmentof the flowmeter control, which would be necessaryas the pressure in the cylinder fell off, is obviated.Because the reducing valve exerts this automaticcontrol it is often referred to as a ‘regulator’.2. By supplying a low gas pressure to thecontrol valve spindle small variations in the gasflow can be made easily. Where a high pressurecylinder is controlled directly by a simple needletypevalve large changes in flow result from verysmall movements of the control valve spindle.3. The regulator limits the pressure within theconnecting tubing to a low level and the likelihoodof bursting the connecting tube when the flow isFIG.9.7 Rotameter.

204 PRINCIPLES AND PROCEDURESof a glass tube inside which a rotating bobbin isfree to move. The bore of the tube graduallyincreases from below upwards. The bobbin floatsup and down the tube, allowing gas to flowaround it. The higher the bobbin in the tube thewider the annular space between the tube andbobbin (orifice) and the greater the flow ratethrough it. The bobbin, usually made of aluminium,has an upper rim which is of a diameterslightly greater than that of the body, and in whichspecially shaped channels are cut. As the gasenters the rotameter tube it impinges on the bobbinand causes it to rise and to spin because the rimwith its set of channels acts like a set of vanes. Theresult is that the bobbin rides on a cushion of gasthereby eliminating errors due to friction betweenthe tube and bobbin. The gas flow rate is read fromthe top of the bobbin against a scale etched on theoutside of the glass tube. If the tube is mounted ina truly upright position these meters are capable ofreadings of an accuracy of ± 2% but only for the gasfor which they have been calibrated.The Heidbrink flowmeter, commonly usedin the USA, has a metal tube, the inside of whichis tapered in the same way as a rotameter tube.The bobbin is replaced by a rod, the tip of whichis visible through a glass tube fitted at the topof the metal tube. A scale is fitted to the side ofthe glass tube and the gas flow rate can be readoff from the position of the tip of the metalrod against this scale. In the UK this type ofmeter is most commonly found on oxygen therapyapparatus.Ball float meters, like the rotameter andHeidbrink, have a tapering bore and are, therefore,variable orifice meters. The bobbin or rod isreplaced by a special ball and if the tube is mountedon an inclined plane one ball is sufficient, but if thetube is vertical the ball tends to oscillate; this isovercome by using two ball floats. The reading istaken from the centre of the ball or, in two balltypes, the point of contact between the balls. TheConnell flowmeter has two balls in contact in aninclined tube. With all inclined tube meters it isimportant that they are set at the correct angle orinaccuracies will occur.A much more crude flowmeter utilizes aBourdon pressure gauge (Fig. 9.8). The gas flowingfrom the cylinder issues from the reducing valveFIG.9.8 Boyle-type vaporizer.This relatively crude typeof vaporizer is not temperature or flow compensated andis mostly used in developing countries for the volatilizationof ether in a stream of O 2 or air.and is made to pass through a small orifice. A pressurebuilds up proximal to the constriction andthis pressure is transmitted to the flexible, metal,oval cross-section, Bourdon tube. The tube tendsto straighten, the degree of straightening dependingon the pressure within it which, in turn,depends on the gas flow through the orifice. Thetip of the Bourdon tube is linked by a simple mechanismto an indicator needle which moves over ascale calibrated in terms of rate of gas flow. In fact,in this meter the gauge indicates the pressure differencebetween the proximal side of the orificeand the atmosphere. This is virtually equivalent tomeasuring the pressure gradient across the orificesince in anaesthetic practice the pressure on thedistal side of the orifice approximates very closelyto atmospheric.The Bourdon type of flowmeter is not satisfactoryfor measuring small rates of gas flow. Owing tothe pressure necessary to cause the Bourdon tubeto straighten out, a very small orifice must be usedto provide the resistance to gas flow. If this orificebecomes partially blocked by dirt the meter readingincreases whereas the actual flow of gas isdecreased; if the orifice becomes completelyblocked the meter reading suggests that the flow isbeing maintained. On the other hand, if the orificeis enlarged due to wear, the gas flow will be

ANAESTHETIC ADMINISTRATION 205increased while the decreased resistance to gasflow will lead to a low meter reading.Pipeline systemsWhere large quantities of oxygen (or other gases)are used, it is more convenient and more economicalto utilize larger cylinders. As these are awkwardto handle they are kept outside the operatingarea and the gas is supplied to the anaestheticmachine through a pipeline. The central depot hasa number of large cylinders connected to a manifoldso that gas is taken from all the cylinders inthe bank. Warning devices are included so that themanifold can be changed to a second bank of cylinderswhen the supply pressure drops, or, withmore complex apparatus where there are two ormore manifolds, the change to the bank of freshcylinders takes place automatically. If extremelylarge quantities of oxygen are used daily, as theymay be in a large hospital, the cylinder bankmay be replaced by liquid oxygen containers butthis is most unlikely to be necessary for veterinarypractice.In the UK the outlets from the pipelines in thetheatre are colour coded and indexed so that atleast in theory, pipes from the anaesthetic machinecannot be connected to the wrong outlet. In practice,it is not unknown for force to be used to circumventthis precautionary system. Oxygen andother gases are delivered at a low pressure to theanaesthetic machine and are fed directly from thepiped supply to the flowmeter. However, mostpipeline machines also carry a small oxygen cylinderand an associated pressure regulator for emergencyuse in the event of a failure in the pipelinesupply.Oxygen failure warning devicesDevices which warn the anaesthetist that the pressureof the oxygen supply is low have been largelyneglected in veterinary anaesthesia, yet it is in thisfield, when often in general practice there is minimalassistance available to monitor the oxygendelivery, where they should be considered anessential feature of anaesthetic machines. Sometypes depend on a second source of gas, usuallynitrous oxide, for their operation. When the oxygenpressure falls a diaphragm moves to allow thesecond gas to pass through a whistle and an easilyaudible warning note is emitted. In other types avalve opens as the oxygen pressure drops and theremaining oxygen passes through the whistle; thewhistling noise ceases as the oxygen pressure fallsto atmospheric pressure.Gases other than oxygenGases other than oxygen which are commonlyfound on anaesthetic machines include nitrousoxide (in the UK cylinders are colour coded blue)and carbon dioxide (grey cylinders). These gasesare compressed in cylinders under a pressurewhich liquifies them at ordinary room temperatures.The amount of gas present in the cylindercan only be found by weighing (all have full andempty weights stamped on them) since the pressureof the gas above the liquid remains almostconstant as long as any liquid remains. Thus, apressure gauge at the cylinder outlet will registeronly a small fall as the gas is being drawn off dueto cooling causing a fall in the saturated vapourpressure, but this will rise again as the cylinderwarms and the pressure registered will not droprapidly until all the liquid has been vaporized andthe residual gas is being drawn off.The saturation pressure of 20°C of N 2 O and CO 2is sufficiently high that the cylinders need to befitted with reducing valves (‘pressure regulators’).It is now possible to mix two gases using amonitored dial mixer unit before delivery into afinal common pathway. This type of system(Quantiflex) has been used for nitrous oxide/oxygenmixtures in any proportions from 21 to 100%oxygen at flow rates of 1–20 l/min. The system iscostly, but it has the advantage that it can be moreconvenient and mistakes are less likely. It is inherentlysafe because hypoxic gas mixtures cannot bedelivered.When an oxygen flow is being mixed with anitrous oxide without the aid of a Quantiflexmixer, failure of the oxygen supply is disastrousbecause the machine will then deliver 100% N 2 O.Oxygen warning devices such as those describedabove reduce the chance of this happeningwithout the knowledge of the anaesthetist, butmany modern machines incorporate a cut-off

206 PRINCIPLES AND PROCEDURESdevice so that should O 2 flow cease the N 2 O flow isalso cut off. This cut-off device may prevent themachine from being fitted with some types of oxygenfailure alarm.VAPORIZERSThe ideal vaporizer would be one that delivered asuitable and accurately known quantity of avolatile anaesthetic agent at all times and under allconditions of use. However, many factors whichvary during the course of administration influencevaporization and only the most modern of expensive,sophisticated pieces of apparatus approachanywhere near this ideal.Factors which have most influence includetemperature, gas flow rate through the vaporizer,and back pressure transmitted during IPPV. Alow resistance to gas flow may also be important ifthe vaporizer is to be used in the breathing circuit(p. 000).Uncalibrated vaporizersIf a liquid volatile anaesthetic is contained in a bottleit is possible to bubble gas through it or to allowthe gas to flow over its surface. This arrangementis sometimes known as a ‘plenum vaporizer’because gas is being forced into a chamber, and‘plenum’ is a chamber or container in which thepressure inside is greater than that outside it.In the UK Boyle pattern vaporizers are stilloccasionally encountered and they are common insome developing countries. In these vaporizers themethod of varying the concentration of anaestheticvapour delivered utilizes a permanent partitionto prevent the direct passage of gases from theflowmeters to the patient. When the control leveris in the OFF position all gases are diverted aroundthe partition but away from the bottle. With the tapin the ON position all gases pass through the bottlecontaining the liquid. The control can be placed inany intermediate position and this determineshow much of the total gas flow passes through thebottle.A further means of controlling the vapour concentrationis also provided. The gases are made topass through a J-shaped tube before emerging intothe space above the liquid anaesthetic in the bottle.The open end of the J-tube is covered by a metalhood which can be positioned as required by movingthe rod attached to it up or down. As the hoodis pushed downwards the gas is deflected nearerand nearer to the surface of the liquid and finally,when the open end of the hood is pushed belowthe surface of the liquid gases are made to bubblethrough the liquid anaesthetic. When the tap is inthe ON position and the hood, or cowl, fullydepressed, the whole of the gas flow is made tobubble through the liquid and a maximum concentrationof the anaesthetic vapour is picked up.Boyle pattern vaporizers for potent agents such ashalothane have a single, straight inlet tube with aside port and no cowl arrangement.When air or other gas flows over the surface of aliquid, the vapour of the liquid is carried away,and is replaced by fresh vapour. This continuousprocess of vaporization is accompanied by a correspondingloss of heat, the magnitude of which isdetermined by the rate at which the vapour isremoved and by the latent heat of vaporization ofthe liquid. The loss of heat results in a fall in thetemperature of the liquid unless heat is conductedto the liquid from some outside source. With a fallin the temperature of the liquid there is a correspondingdecrease in the speed of vaporizationand, if the gas flow remains constant, the concentrationof anaesthetic vapour in the gas streamfrom a Boyle pattern vaporizer decreases withtime until the heat loss due to vaporization is balancedby the conduction of heat through the glassbottle from the surrounding atmosphere. Whenether was used in this type of vaporizer it was notuncommon to see ice crystals forming on the outsideof the bottle as its temperature fell due tovolatilization of the ether.Calibrated vaporizersThere are today many precision vaporizers on themarket, all designed to deliver an accuratelyknown concentration of specific volatile anaestheticsover a wide range of gas flow rates. They consistof a vaporizing chamber and a bypass. Thefresh gas stream flowing into the vaporizer isdivided into two portions, the larger of whichpasses straight through the bypass. The smallerportion is ducted through the vaporizing chamber

ANAESTHETIC ADMINISTRATION 207where it becomes saturated with the vapour, andthis ensures that:1. There is no sudden burst of high vapourconcentration when the vaporizer is firstswitched on.2. The output of the vaporizer is unaffected byshaking.As already pointed out, vaporization of the liquidanaesthetic results in the removal of heat from theliquid with a resultant fall in its temperature.Modern calibrated vaporizers are constructedfrom metal (mainly copper) which ensure theready conduction of heat from the room to the containedliquid, the high thermal conductivity of themetal container together with the high thermalcapacity of its mass, ensure a sufficient supply ofheat for vaporization, holding the liquid temperatureconstant. In these modern vaporizers the onlycontrol to set is the output concentration.A major problem in vaporizer design lies in thedesign of the splitting valves. In the earlier types itproved impossible to ensure that the flow divisionof this valve remained constant over a widerange of flow rates, and the vaporizers weresupplied with graphs which needed to be consultedto determine the concentration of volatileagent being delivered when they were usedwith gas flow rates below 4 l/min. In currentmodels this problem has been overcome and itis generally accepted that most deliver accuratelyindicated concentrations at flow rates above500ml/min.Pressure fluctuations produced by IPPV have apumping effect and this may have a considerableeffect on the output, even doubling the output concentrationat low gas flow rates. Modern vaporizersincorporate a non-return valve to overcomethis.The volatile anaesthetic agent, desflurane,requires a special vaporizer as its boiling point istoo close to room temperature for it to be used inthe conventional systems.The ‘Selectatec’ and similar systems enable theeasy removal or placement of the vaporizer on the‘back bar’ of the anaesthetic machine for filling inanother environment, or for exchange for a vaporizercontaining a different anaesthetic agent or forservice. Calibrated vaporizers need regular serviceat intervals as recommended by the manufacturersif they are to retain their accuracy.All the vaporizers described so far have a highresistance to gas flow, which is unimportant whenthe carrier gas is pushed through them by thepower of the compressed gases in the cylinders orpipelines. However, if the vaporizer is to be usedwhere the gas flow is powered by the respiratoryefforts of the animal, then a low resistance vaporizeris essential and vaporizers of this type are necessaryfor use in ‘in-circle’ systems.Low resistance vaporizersVaporizers offering a low resistance to gas flow areusually of a simple type with wide-bore entry andexit ports and no wicks to impede the flow ofgases. A simple low resistance, low efficiencyvaporizer of this type often used in dental surgeryis the Goldman (Fig. 9.9).The EMO vaporizer (Epstein-Macintosh-Oxford) (Fig. 9.10) was specifically designed forthe volatilization of ether and is generally recognizedas the best of this type of vaporizer. It isFIG.9.9 Goldman vaporizer for inclusion in thebreathing system.Commonly used for halothane.

208 PRINCIPLES AND PROCEDURESagreed system. A system of classification formerlyin common use in the UK was:1. The open method2. The semi-open method3. (a) The closed method with carbon dioxideabsorption (b) The semi-closed method withcarbon dioxide absorption4. The semi-closed method without carbondioxide absorption.This classification has been criticised on thegrounds that it is impractical and does not fit allsystems. A more clinically useful definition of systemsis based on the two methods by which carbondioxide is removed from the inspired gases:1. Non-rebreathingThe system is designed so that the expired gasesare vented to the atmosphere and cannot berebreathed.2. RebreathingThe expired gases are passed through anabsorber which contains soda lime or anotherabsorbent (e.g. Baralyme) to remove the carbondioxide.FIG.9.10 The EMO vaporizer for ether.This draw-over,temperature compensated unit may be used in situationswhere supplies of O 2 are not readily available and,consequently,it is very popular in some developingcountries.portable, has a temperature compensating deviceand is employed in a non-rebreathing system.Ether/air anaesthesia administered from it meetscriteria for acceptability in general practice wherethe veterinarian may be assisted in the operatingtheatre by a nurse or may be entirely alone. It maybe used in situations where supplies of oxygen arenot readily available and, consequently it is popularin many developing countries.BREATHING SYSTEMSThe purpose of the breathing system is to conveyoxygen and anaesthetic to the patient, and toensure the removal of carbon dioxide produced bythe patient. It does not seem possible to classify allthe ways in which this can be done in a completelylogical manner and as yet there is no universallyThe open and semi-open methods were used tovolatilize agents such as chloroform and ether. Themethods are often referred to as ‘rag and bottleanaesthesia’ and they survived through over ahundred years of anaesthetic history. In the semiopenor ‘perhalation’ method all the inspired airwas made to pass through a mask on which thevaporization of the agent occurred. In horse andcattle special masks were often used for the semiopenadministration of chloroform. These maskswere cylinders of leather and canvas applied overeither the upper or both jaws. Chloroform wasapplied to a sponge inserted in the open end of thecylinder. In the cruder types of mask the spongewas actually in contact with the nostrils, but inmore refined patterns a wire mesh partition preventedthis direct contact.Today, the open and semi-open methods ofadministration are seldom used. In them, theanaesthetic agents are diluted to an unknownextent by air and this dilution is greatest whenthe minute volume of breathing is large so theinspiratory gas flow rate is high. The greater theventilation (and hence, the dilution of the anaes-

ANAESTHETIC ADMINISTRATION 209thetic inhaled), the closer the alveolar concentrationof the anaesthetic will approach zero, andanaesthesia lightens as ventilation increases. Onthe other hand, depression of breathing decreasesthe air dilution and thereby increases the concentrationof anaesthetic inspired. Under thesecircumstances unless there is an increase in theuptake of the anaesthetic by the body, the alveolarconcentration of the anaesthetic must rise. A risein the alveolar concentration produces deeperunconsciousness and further respiratory depression.In addition, deepening anaesthesia reducesthe cardiac output and hence the uptake of anaestheticby the body, thus adding still further to therise in the alveolar concentration. If this process isallowed to proceed unchecked, unconsciousnessdeepens until the ventilation becomes inadequate.In other words, with the open and semi-openmethods of administration, animals which becomemore lightly anaesthetized tend to continue awakeningand animals which become more deeplyanaesthetized tend to continue becoming moredepressed and nearer to death.ABCDEFGFGFGFGPPPPPMAPELSONSYSTEMSNON-REBREATHING SYSTEMSThe general principle behind non-rebreathing systemsis that the fresh gases flow from the anaestheticmachine into a reservoir from which the patientinhales and the exhaled gases are spilled, usuallythrough an expiratory valve, to the atmosphere.Carbon dioxide removal depends on the fresh gasflow rate, and on the tidal and minute volumes ofrespiration of the patient. Many systems have beendevised but, in general, they are all variations ofthose classified by Mapleson (1954). The performanceof many of these systems has been reviewedby Sykes (1968). Strictly speaking, they often cannotbe regarded as non-rebreathing systemsbecause some rebreathing of exhaled gases takesplace, but they are operated to ensure that thisrebreathed gas constitutes no more than the gascoming from the deadspace of the animals’ respiratorytract, i.e. fresh gas in so far as the inhaled concentrationof anaesthetic gases is concerned. Inveterinary anaesthesia the most commonly usednon-rebreathing systems are the Magill (MaplesonA), the T-piece (Mapleson E) and coaxial circuits(variations of Mapleson A and D) (Fig. 9.11).FFIG.9.11 The Mapleson classification of patientbreathing systems. A:Magill and Lack circuits;E:T-piecesystem;FG:fresh gas flow;P:patient.The Magill systemThe Magill attachment, which incorporates areservoir bag, wide bore corrugated tubing and aspring loaded expiratory valve is probably themost generally useful of all the non-rebreathingsystems. With this system rebreathing is preventedby maintaining the total gas flow rate slightly inexcess of the patient’s respiratory minute volume.The animal inhales from the bag and wide boretubing; the exhaled mixture passes back up thetubing displacing the gas in it back into the bagFGFGP

210 PRINCIPLES AND PROCEDURESFresh gasflowalveolar gasearly inspirationlate inspirationearly expirationlate expirationdeadspace gasFIG.9.12 The Magill system (spontaneous breathing)showing the mode of operation to prevent rebreathing ofexhaled gas.until it is full. The exhaled gases never reach thebag because the capacity of the tube is too greatand once the bag is distended the build up of pressureinside the system causes the expiratory valveto open so that the terminal part of expiration (richin carbon dioxide – the alveolar gas) passes out ofthe valve into the atmosphere. During the pausewhich follows expiration and before the next inspirationfresh gas from the anaesthetic apparatussweeps the first part of the exhaled gases from thecorrugated tube out through the expiratory valve(Fig. 9.12).To ensure minimal rebreathing of the expiredgases the fresh gas flow rate should be equal to, orgreater than, the minute volume of respiration ofthe patient. However, as the system leads to thepreferential removal of alveolar gas, a lower freshgas flow rate (equal to the alveolar ventilation)may be adequate and, in man, Kain and Nunn(1968) have shown that in spontaneously breathingpatients significant rebreathing does not occuruntil the fresh gas flow rate falls below 70% of thepatient’s minute volume. If, however, IPPV isapplied by compression of the reservoir bag, thenvery much higher fresh gas flows are needed toprevent rebreathing because under these circumstancesthe fresh gas is spilled through the expiratoryvalve at the end of inspiration.Various non-return valves have been incorporatedin the Magill system in place of the simplespring loaded expiratory valve. All these valvesprevent any rebreathing of the exhaled gases otherthan those contained in the valve itself and its connections.Where they are used the gas flow ratesfrom the apparatus require frequent adjustment,for any alteration in the rate or depth of thepatient’s breathing affects the degree of distensionof the reservoir bag. If the gas flow rate is kept constant,deep or rapid breathing empties the bagquickly, while slow or shallow breathing allowsthe bag to become over distended. These nonreturnvalves can be used to measure the minutevolume of respiration for if the flow rates areadjusted to maintain the bag at a constant averagesize at the end of expiration the total flow rate asread from the flowmeters will equal the respiratoryminute volume. In practice because of thenecessity for repeated adjustments of the total gasflow rate, an excessive flow is employed and a spillvalve is incorporated between the reservoir bagand the non-return valve.The T-piece systemThe low resistance and small deadspace make theT-piece system, first described by Ayre in 1937,very suitable for small dogs and cats. As shown inFig. 9.13 an open tube acts as a reservoir and thereare no valves. The exhaled gases are swept out ofthe open end of the reservoir tube by fresh gasesflowing in from the anaesthetic apparatus duringthe expiratory phase. Unless the capacity of thereservoir tube is at least equal to the tidal volumeof the animal the terminal part of inspiration willbe air, but unless its capacity is very small this isunimportant for the air will only enter the respiratorydead-space and no dilution of the anaestheticgases will take place.

ANAESTHETIC ADMINISTRATION 211fresh gas flowearly inspirationsuit the circumstances. Scavenging of waste gasesfrom the T-piece system presents some difficultiesif the overall resistance of the apparatus is not to beincreased.alveolar gasdeadspace gasfresh gas flowfresh gas flowfresh gas flowlate inspirationearly expirationlate expirationFIG.9.13 Mode of operation of the T-piece system inpreventing rebreathing provided the fresh gas flowexceeds about twice the patient’s minute volume.The resistance and fresh gas requirements areobviously related to the expiratory flow rate andflow patterns which occur in animals of any particularsize. The minimum fresh gas flow raterequired to prevent rebreathing and air dilutionduring both spontaneous and controlled ventilationis generally recommended to be 2.5 – 3.0 timesthe minute volume of respiration, provided theexpiratory limb has a capacity greater than thetidal volume.Using the basic T-piece system IPPV may beapplied by intermittently blocking the open end ofthe reservoir tube thus directing the fresh gas intothe animal’s lungs. However, the inflation pressure,being that supplied by the anaestheticmachine, may be so high as to cause massive pulmonarydamage if over inflation is allowed tooccur. Ventilation may be controlled more safelyby squeezing an open-tailed bag attached to theend of the expiratory limb – the Jackson–Reesmodification. The orifice of the open tail can becontrolled between the finger and thumb of theanaesthetist and the inflation pressure adjusted toCoaxial systemsThe desirability of controlling atmospheric pollutionin operating theatres has led to an interest inthe use of coaxial circuits because it is relativelyeasy to duct the waste gases from them to theatmosphere by valves placed at the anaestheticmachine and well away from the patient. The Bain(Fig 9.14) and the Lack (Fig. 9.15) systems are twotypes of coaxial circuits.In the Bain system fresh gas passes up the centraltube and expired gas through the outer sleeve.It can be seen that this arrangement is basicallythat of the T-piece system and, therefore, in general,the same gas flow considerations will apply.However, higher gas flow rates are needed to preventrebreathing of expired gases during spontaneousrespiration and the pattern of respiration isimportant. These high flows directed via a narrowpipe to the animal’s airway themselves cause quitemarked expiratory respiratory resistance througha venturi effect. An animal which breathes slowlywith a long expiratory pause will make more efficientuse of the fresh gas inflow than an animalwith a rapid, shallow respiratory pattern.The Lack circuit uses the alternative arrangementin which the fresh gas flows in the outersleeve and expiration through the inner tube. Thisarrangement was designed to aid scavenging ofexpired gas and is more satisfactory than the conventionalMapleson A system in this respect. TheLack system cannot be used with controlled ventilationin the same way as the Bain system withoutexcessive rebreathing so its use is restricted tospontaneously breathing animals.The modified Bain system collects the expiredgas in a reservoir bag connected to a blow-offvalve at the end of the expiratory tube and hasproved reasonably satisfactory for use in dogsover 10kg body weight. Compression of this reservoirbag or the introduction of air during the inspiratorycycle of a ventilator connected to the bagmount gives very good results for IPPV in dogsover 20kg body weight.

212 PRINCIPLES AND PROCEDURESFGFFGFPatientAPatientAFGFPatientBFGFPatientBFGFPatientCFGFPatientDFGFPatientCFIG.9.14 The T-piece system (A) compared to theoriginal Bain coaxial system (B),the modified Bain system(C) and the modified,parallel Bain system (D).It isimportant to note that in the modified systems the bag ison the expiratory limb (FGF:fresh gas flow).Use of these coaxial systems in veterinary anaesthesiahas revealed a number of problems. In somecases the internal or external tubing has been ofsuch a small bore that excessive demands weremade on the animal’s inspiratory or expiratoryefforts. More serious, perhaps, the inner tube maybecome detached from the anaesthetic machine orthe patient resulting in a very large deadspace.The potential for a large increase in deadspaceif the inner tube of a coaxial system becomesdetached at the end nearest the anaestheticmachine has been appreciated in respect of theBain system for some considerable time and it ismost important that the system is tested immediatelybefore use. Testing may be done by connectingit to the common gas outlet of the anaestheticmachine and passing a flow of at least 6 l/min ofoxygen through the inner tube of the system. Thedistal (patient) end of this inner tube is thenFIG.9.15 The Lack coaxial system (B) compared to thestandard Magill system (A) and the parallel Lack system(C).In all these systems the bag is on the inspiratory limb ofthe system (FGF:fresh gas flow)occluded (with the finger or the plunger of a 5mlsyringe) and the oxygen flowmeter bobbin shouldbe seen to dip and the machine pressure reliefvalve heard blowing off, indicating that all is well.Parallel systems which operate in the samemanner as the Bain and Lack systems have twotubes running alongside one another rather thanone inside the other (Figs 9.14 & 9.15). Althoughperhaps slightly more cumbersome, faults in thesystems are more easily recognized.Modifications of non-rebreathing systemsThe Humphrey ADE system is designed to facilitatechanging from a Mapleson A configurationduring spontaneous ventilation to a Mapleson Dor E mode during controlled ventilation. Recentlythe system has been adapted to include the optionaluse of a carbon dioxide absorber. Resistance

ANAESTHETIC ADMINISTRATION 213in the system is reduced by the use of a flat (noncorrugated)lining to the tubing, which reducesturbulence. In man, the system has proved suitablefor use in adults and children. To have one systemadaptable for rebreathing, non-rebreathing, spontaneousand controlled ventilation for all sizes ofcats and dogs would be of great convenience inveterinary practice. The Humphrey system hasproved suitable for dogs weighing from 5.4–89.0Kg(Lilja et al., 1999), but its use in smaller dogs or catshas yet to be investigated.The Maxima breathing system (Miller 1995)also can be used for both controlled and spontaneousventilation. It is a lightweight valveless nonabsorbersystem that allows selective eliminationof alveolar gas in both spontaneous and controlledventilation modes. In spontaneous ventilationmode it behaves as a Mapleson A system.Flow rates required in non-rebreathingsystemsNon-rebreathing systems have major advantagesin that they may have low deadspace and resistance,and the anaesthetist knows the concentrationof gases which the animal is breathing. Their disadvantageis the wastefulness of using high flowrates of gases. Although most textbooks advocatethe need for administering the minute volume (forMapleson A systems) or more (Mapleson E), a surveyof existing literature demonstrates that thereare few recommendations as to what is the minutevolume of a particular type of animal. Most studieshave suggested that tidal volume ranges from10–20 ml/kg in dogs (Clutton 1995), and respiratoryrate may be counted in order to obtain minutevolume (this is not accurate if the dog is panting).A second approach is to set flow rates based onml/kg/minute. With a Mapleson A circuit the flowrates recommended to prevent rebreathing areapproximately 130ml/kg/minute for dogs weighingless than 10 Kg, and 95 ml/kg/min for thoseweighing more (Holden, personal communication;Waterman 1986; Lilja et al., 1999). The highermetabolic rate of the smaller animal provides anexplanation for the differences in requirement inrelation to weight, and it has been suggested that itshould be possible to find a single suitable flowrate for a moderately wide range of weights. Liljaet al. (1999) has demonstrated that with aMapleson A circuit, a flow rate of 4 l/min. wassufficient to prevent rebreathing in all but one of 49dogs, weights ranging from 5.4 – 89.0kg, but onedog (not the heaviest but with a weight of 59 kg)required a flow of 5 l/min. The disadvantage ofusing any of the set ‘formulae’ discussed above isthat in order to ensure that flow rates are adequatefor every single animal, they will be excessive formany, leading to waste and expense. Ideally,where there is the ability to monitor end tidal carbondioxide, gas flows can be reduced to those justsufficient to prevent rebreathing, and where this ispracticable, it will be found that for small animalsnon-rebreathing circuits can be used with minimalexpense.REBREATHING SYSTEMSAnaesthetic gases and vapours are said to be moreor less physiologically ‘indifferent’, in that they arelargely exhaled from the body unchanged, butwhen exhaled they are mixed with carbon dioxide.The exhaled gas can be directed into a closed bagand if the carbon dioxide is removed, and sufficientoxygen added to satisfy the metabolicrequirements of the animal, the same gas orvapour can be rebreathed continuously from thebag. This is the principle of closed system anaestheticadministration. The same apparatus mayalso be employed as a ‘low flow’ system if slightlyhigher gas flow rates are fed in and the excessgases allowed to escape through an overflowvalve.In anaesthesia, the carbon dioxide is usuallyremoved by directing the exhaled mixture over thesurface of soda lime. This is a mixture of 90% calciumhydroxide and 5% sodium hydroxide togetherwith 5% of silicate and water to preventpowdering. It is used in a granular form, the granulesbeing 4–8 mesh in size, and ideally packed in acontainer so that the space between the granules isat least equal to the tidal volume of the animal.Some brands of soda lime contain an indicator dyethat changes colour (e.g. from white to violet)when the carbon dioxide absorbing capacity isexhausted. Absence of visible colour change is noguarantee that the soda line is capable of absorbingmore carbon dioxide – a small quantity should

214 PRINCIPLES AND PROCEDURESbe wrapped in gauze and a brisk flow of carbondioxide directed through it. When this is doneactive soda lime becomes very hot but exhaustedabsorbent remains cool. Unfortunately, the modernpractice of removing carbon dioxide suppliesfrom anaesthetic machines means that this simpletest may be impossible to carry out although simplybreathing out over a small quantity is effective,albeit taking a longer time, for the heat change tobecome palpable. When a capnograph is availablethe inspired gases should not contain more than0.1 to 1% of carbon dioxide and thus any rise in theinspired concentration of this gas in a circle systemmay be the only indication that the soda lime isexhausted. Due to the exothermic nature of thereaction between soda lime and carbon dioxide,the soda lime container should become warm asanaesthesia proceeds and this should be detectableif absorption is efficient.Theoretically, during closed circuit administration,once anaesthesia has been induced and a stateof equilibrium established, all that the animalrequires from the apparatus is a continuous streamof oxygen just sufficient to satisfy its metabolicneeds, and efficient absorption of carbon dioxide.In practice, however, most periods of anaesthesiaare too short to allow a state of equilibrium to bereached and the body continues to take up theanaesthetic agent throughout the administration,so that the agent has to be given all the time inorder to maintain the alveolar concentration.The closed method of administration is simple,and much less anaesthetic is used than in nonrebreathingmethods because there is no wastage tothe atmosphere. The chief disadvantage of closedsystem anaesthesia was assumed to be the resistancedue to the packed soda lime and this resistancewas considered sufficiently great to render themethod unsuitable for cats, puppies and very smalladult dogs. These reservations were applied to theuse of systems designed for use in human adultsfor these small veterinary patients. Although themechanical deadspace imposed by some of theY-piece connectors was excessive, physiologicalfactors such as muscle fatigue, inefficient ventilationand a tendency to lung collapse were probablyresponsible for some of the respiratory problemsobserved in small animals breathing spontaneouslyfrom systems designed for use with adulthumans. Another disadvantage is that the conservationof heat and water vapour afforded by themethod may give rise to heat stroke in dogs andsheep if the ambient temperature is high.There are two systems in use for carbon dioxideabsorption in anaesthesia:1. The ‘to-and-fro’ system2. The ‘circle’ system.The ‘to-and-fro’ systemA canister full of CO 2 absorbent is interposedbetween animal and the rebreathing bag, freshgases being fed into the system as close to the animalas possible to effect changes in the mixturerapidly (Fig 9.16A). This system is simple but hasseveral drawbacks. It is difficult to maintain theheavy, awkward apparatus in a gas-tight conditionand the inspired gases become undesirably hotdue to the chemical action between the soda limeand the carbon dioxide. Furthermore, irritatingdust may be inhaled from the soda lime and giverise to a bronchitis. Nevertheless, the system hasbeen most commonly used in veterinary anaesthesiafor the necessary apparatus is relatively inexpensiveand may be improvized.For small animal anaesthesia (dogs, sheep andgoats, young calves, young foals and small pigs)the standard soda lime canisters used in man,which are known as Water’s canisters after theirdesigner, are quite satisfactory. They are availablein various sizes: one containing 1lb (approx 0.5kg)and a second one containing 10oz (approx 0.3kg)of soda lime are adequate for most veterinary purposes.These canisters are used horizontally andunless the soda lime is tightly packed when thecanister is filled it tends the settle, leaving a channelalong the top through which gases may passfollowing the path of least resistance withoutbeing subjected to the action of the soda lime. Inthe larger canisters a domestic nylon pot-scrubmay be used so as to leave about half of it to becompressed by the wire gauze in the lid of the canisterwhen the cap is screwed on.Adult horses, cattle and large pigs need muchlarger soda lime canisters. They are designed onthe principle that the animal’s tidal volume shouldbe accommodated in the spaces between the sodalime granules. Because of the difficulty of packing

ANAESTHETIC ADMINISTRATION 215FGFsoda limesoda limethese canister sufficiently tightly with soda lime,special to-and-fro canisters have been designedand developed for large animals. The vertical positionof these soda lime canisters means that tightpacking is not necessary and their cross-sectionalarea is large to ensure than the respired gases passthrough the absorbent slowly. For adult horses andcattle a rebreathing bag having a capacity of about15 l is used.The to-and-fro systems can never be reallyefficient absorbers of carbon dioxide. The exhaledgases all come into contact with the soda limeat the end of the canister nearest to the patientand the absorbent in this region is quickly exhausted.Thus, as this occurs, the gases haveto travel further and further into the canisterbefore carbon dioxide is absorbed or, in otherwords, the apparatus deadspace steadily increasesduring anaesthesia. Thus, ideally the absorbent inthese circuits should be changed between everycase.The ‘circle’ systemvalvevalveFGFPatientFIG.9.16 To-and-fro (A) and circle absorber(B) systems (FGF:fresh gas flow).PatientThe circle system for carbon dioxide absorptionincorporates an inspiratory and an expiratory tubewith unidirectional valves to ensure a one-wayflow of gases; the rebreathing bag and soda limeABcanister are placed between these tubes. The valvesand tubing offer an appreciable resistance tobreathing and unless the apparatus is carefullydesigned with regard to the diameter of airways inrelation to flow rates, breathing through the apparatuscan impose a considerable strain on theanimal, and the inevitable degree of rebreathingwhich occurs at the T-piece connexion to the patientlimits the removal of CO 2 from the exhaled gas.This rebreathing can be prevented by placing theunidirectional valves at the face-piece or endotrachealtube connection, but it is difficult to designrobust, competent valves for use at these situations.In the majority of modern circle type units the unidirectionalvalves are of the turret type; they arerobust and competent but must be kept upright andof necessity, therefore, have to be mounted on theapparatus at some distance away from the animal.Circle absorber units (Fig. 9.16B) are more efficientabsorbers of carbon dioxide than are to-andfrounits because their dead space is constant sinceall the charge of soda lime is available to therespired gases. Exhaustion of soda lime is noticedmore suddenly than in to-and-fro absorbers andonce it occurs the inspired carbon dioxide concentrationmay soon become excessive.To avoid this sudden exhaustion of soda limeand for economy in its use, canisters are now oftenmade with two compartments. The compartmentof the canister which first receives the expiredgases and, therefore, whose soda lime is first used,can be refilled and the position of the canisterreversed so that expired gases pass through theremaining partially used soda lime, using this tocomplete exhaustion before reaching the newlyfilled compartment.Standard circle absorbers designed for man aresatisfactory for spontaneously breathing youngfoals, young calves, sheep, goats, most pigs, anddogs over 15 kg body weight. Circle absorbers forlarge animal patients are now readily available fromcommercial sources but there are few reports of theirefficiency in terms of carbon dioxide absorbingcapacity or resistance to breathing. In NorthAmerica human paediatric circle absorbers are oftenused for small dogs (and even cats) but they havenever found favour in the UK for patients of thissize. In adapting circle systems for use in small animals,it was originally assumed that all components

216 PRINCIPLES AND PROCEDURESof the standard adult human systems should bereduced in proportion to the size of animal in orderto minimize deadspace and resistance to breathing.Several minaturized circle systems were manufactured,of which the Bloomquist and Ohio InfantCircle Systems are probably the best known (Dorsch& Dorsch, 1975). However, it was an error to assumethat smaller valves would result in less resistance tobreathing because resistance is inversely proportionalto the diameter of the valve (Hunt, 1955).Moreover, being non-standard apparatus, all thesesmall animal circle systems involve a considerablenuisance factor for the anaesthetist, requiring a completechangeover from standard adult human systems.The general practice in medical anaesthesiatoday is to anaesthetize paediatric patients usingstandard adult size apparatus but with IPPV overcomethe physiological factors such as musclefatigue and inefficient ventilation involved.Practical problems involved in the use ofclosed rebreathing systemsAll anaesthetists using closed rebreathing systemsmust fully understand how the concentrations ofgases which the animal breathes from the reservoirbag are altered by the uptake, utilization, and eliminationof gases and vapours by the patient.When anaesthesia is first induced with aninhalation anaesthetic the animal takes up theanaesthetic and the expired gases contain a lowerconcentration of the anaesthetic than in theinspired gases. Thus, the concentration of anaestheticin a completely closed circuit will be diluted.The speed of uptake of the anaesthetic depends onmany factors (Chapter 6) but the larger the animal,the greater the dilution, and the longer the timebefore equilibrium is attained. Also, during induction,nitrogen from the patient accumulates in theanaesthetic circuit and decreases the concentrationof O 2 therein.The problems of denitrogenation and of maintainingan adequate concentration of anaestheticfor the induction of anaesthesia are best overcomeby increasing the fresh gas flow rate, opening overspillvalves, frequently emptying the rebreathingbag (‘dumping’) and thus converting the systeminto a semi-closed system for the duration of theinduction period. Rapidly decreasing the depth ofanaesthesia presents problems similar to thoseencountered in induction of anaesthesia but thegases exhaled by the patient will contain anaestheticin higher concentrations than the inspiredgas, so that the concentration in the breathingcircuit will tend to increase, and the depth of anaesthesiawill only lighten very slowly. Again, this canbe overcome by increasing the gas inflow rates andemptying the rebreathing bag at frequent intervals.When a completely closed rebreathing system isemployed maintenance of a stable depth of anaesthesiaalso poses problems. Theoretically, all that isrequired is a fresh gas inflow containing exactly theoxygen requirements of the animal together withlow concentrations of the anaesthetic just sufficientto replenish that being absorbed by the patient orlost from the wound surfaces etc. In large animalswhere the oxygen need exceeds 1l/min., the completelyclosed system works well and can be usedthroughout the anaesthetic maintenance period. Insmall animals, however, it is often difficult to maintainsmooth stable anaesthesia without extremecare being paid by the anaesthetist to every aspectof administration. This is because these smallanimals have very low basal metabolic requirementsof oxygen and the vaporizers used todeliver volatile anaesthetics are often very inefficientat low gas flow rates. Even modernvaporizers only deliver accurately known concentrationsof the volatile agents with carrier gasflow rates of more than 0.5 l/min. and stableanaesthesia can only be achieved by increasingthe fresh gas flow rate to a level at which the vaporizerwill deliver an accurately known concentrationsof anaesthetic, and allowing the excessto escape from an overflow valve. Some veterinariansattempt to overcome these problems by fillingthe circuit intermittently with high fresh gasflow rates but this results in fluctuating levels ofanaesthesia.A second method of overcoming the problem ofvaporization of the anaesthetic at low fresh gasflow rates is to place the vaporizer inside thebreathing system. If the vaporizer is placed in thefresh gas supply line outside the breathing systemthe system receives a steady supply of anaesthetic.When the vaporizer is placed in the breathing circuit(vic), however, the flow through it depends onthe respiratory efforts of the patient so that vapori-

ANAESTHETIC ADMINISTRATION 217zation of the anaesthetic depends on this ratherthan the fresh gas flow rate.All anaesthetists using vaporizers inside thebreathing circuit must understand clearly the wayin which the alveolar concentration and hence thedepth of anaesthesia, is dependent on the factorsof ventilation, fresh gas inflow and vaporizer characteristics.In general, when the vaporizer is in thebreathing circuit:1. If anaesthesia is too light surgical stimulationwill lead to increased ventilation and adeepening of unconsciousness. A sudden increasein ventilation and, therefore, of inspired concentrationmay be dangerous.2. If the vaporizer setting is too high, deepeninganaesthesia depresses ventilation and reducesvaporization. This acts to some extent as a built-insafety factor.3. If the animal stops breathing no fresh vapourenters the circuit.4. The smaller the fresh gas inflow thegreater the economy in the use of the volatileagent.5. A simple, low efficiency vaporizer is all thatis required (e.g. The Goldman vaporizer for halothanewhich limits the concentration delivered toless than 3% by volume whatever the gas flowthrough it).6. The safety of the circuit will depend on theanaesthetic agent. The concentration achieved willdepend on the volatility of the agent, and thesafety of that concentration on the MAC of theagent. For example, the boiling points and thusthe concentration achieved at any setting of thevaporizer for halothane and isoflurane are similar,but as the MAC of isoflurane is higher, theoreticallyits use should be safer in this system thanhalothane (Laredo et al., 1998). The boiling point ofsevoflurane is higher, its MAC is 2.5%, and it hasproved necessary to increase the efficacy of thestandard vaporizer by adding a wick in order touse sevoflurane efficiently in a VIC (Muir &Gadawski, 1998). The low boiling point ofdesflurane means that it would be impossible touse in such a vaporizer.7. The fact that respired gases pass through thevaporizer introduces problems of resistance tobreathing.There is wide concern among anaesthetists thatinadvertent high flows through the vaporizer maylead to undesirably high concentrations of the volatileagent accumulating in the circuit during assistedlung ventilation with consequent danger fromoverdose. However, used cautiously with, if possible,monitoring of the circuit concentrations of thevolatile agent the method can be very satisfactory.When the vaporizer is outside the breathingsystem:1. Ventilation has no effect on vaporization.Assisted or controlled respiration by IPPV haslittle effect on the depth of anaesthesia and istherefore much safer than is the case when thevaporizer is in the breathing system.2. In most instances for any particular setting ofthe vaporizer control the smaller the fresh gasflow, the lower is the inspired concentration.3. Too deep anaesthesia with respiratory depressiondoes not have the built in safety factorfound when the vaporizer is in the breathingsystem and the animal is in the breathing spontaneously.Because of the difficulties with both in-circuitand out-of-circuit vaporizer positions manyworkers are adopting a simple system of injectingthe liquid volatile agents directly into theclosed breathing system. Vaporization takesplace inside the tubing of the system and ametal sleeve with or without some gauze may beused to aid vaporization. Drip feeds of liquidanaesthetics into anaesthetic systems werecommon in the past but current interest is inthe injection of liquid anaesthetic into the systemusing an electrically driven syringe pumpwhich greatly facilitates automatic, computercontrol. Using a monitoring device in the inspiratorylimb it is possible to set up a computerassisted system to maintain a constant inspiredconcentration of the anaesthetic agent. The closedcircuit system also lends itself to various methodsof automatically controlling gas flow into the system.One sophisticated approach uses a concertinabellows in the circuit as a volume transducerwhich is attached to a linear transducer to controlthe inflow of oxygen and nitrous oxide. In thissystem the gas flows can be electrically controlled

218 PRINCIPLES AND PROCEDURESto produce any desired flow rate from 50 to1000ml/min with an accuracy of ±1%, an oxygensensor controlling oxygen flow to maintain apredetermined concentration and the nitrousoxide to maintain the volume. Work with suchsystems for veterinary use has been reported byMoens (1985).The influence of the location of the vaporizer onthe inspired tension of the anaesthetic agent mustalways be taken into account. Each placement hasits own advantages and disadvantages, but in thehands of an experienced anaesthetist eitherarrangement is equally safe (or unsafe). The inexperiencedanaesthetist is advised, especially withpotent anaesthetics such as halothane or isoflurane,to use a calibrated and preferably thermostaticallycontrolled vaporizer placed outside thebreathing system.DEFINITION OF ANAESTHETIC SYSTEMSThere have been many multiple and inconsistentdefinitions in British and North American literatureand, as yet, there is no universal nomenclature.The systems of terminology consist of‘closed’ and ‘open’ themes with variations, butthis terminology is now of very little value.Moreover, these systems attempt to use rebreathingas the distinguishing factor. Althoughrebreathing is an extremely important variable, itis impossible to describe accurately variationswhich occur in the degree of rebreathing by the useof such terms as semi-closed, semi-closed withabsorption, partial rebreathing, etc. It appears tobe agreed by most workers that semi-closed refersto partial rebreathing techniques. Thus, for example,a system which has nearly complete rebreathingof the expired gases might have the same labelas a system which has almost no rebreathing.Clearly this system of nomenclature may allowerroneous interpretations concerning the actualinspired concentration or tension of any inhalationanaesthetic. In order to clarify matters so that readersof an account of a procedure reported in anypaper or book can obtain an exact picture of whatwas actually done, regardless of variations ofteaching, practice and geographical location, it isonly necessary for an author to give two simplepieces of information. First, the actual equipmentused needs to be described (T-piece, etc.), and second,the fresh gas flow rate should be stated. Thesetwo basic items of information need only besupplemented under certain, special circumstances.For example in certain communications itmight be necessary to give details such as the exactapparatus deadspace volume, types of valves,type and location of vaporizer (in or out of thebreathing circuit), etc. For the majority of communicationssimply stating the apparatus used and theflow rates of gases would be quite adequate. It is tobe hoped that authors will adopt this simple expedientso easy exchange of accurate information sovital to patient’s welfare, teaching and research,will become a possibility in veterinary anaesthesia.FACE MASKS AND ENDOTRACHEALTUBESAnaesthetics given by any method must be deliveredto the animal through a well fitting face maskor endotracheal tube or the anaesthetic agent willbe diluted and inhaled with an unknown quantityof air.ANAESTHETIC FACE MASKSIn domestic animals there are wide variations inthe configuration and size of the face in any onespecies, so that it is difficult to obtain an accurateairtight fit between the face and a mask. However,this difficulty can be overcome by the use of malleableconstructions of latex rubber (Figs. 9.17 &9.18) which can be moulded around the face.Another type of mask for small animals makes useof rigid transparent cones fitted with a perforatedthin rubber diaphragm to provide an air-tight sealaround the face. This latter type are difficult toapply for IPPV of the lungs and should be avoidedif the mask is to be left in place for any length oftime for the tightly fitting rubber diaphragm cutsoff the venous return from the muzzle and cancause cutaneous oedema. In small animals thelower jaw must be pushed forward into the maskfor if it is displaced backwards the airway maybecome obstructed by the base of the tonguecoming into contact with the posterior wall of the

ANAESTHETIC ADMINISTRATION 219ensure that the nostrils are not obstructed by cominginto contact with the mask. Some patterns offace mask are made of transparent material toallow the anaesthetist to observe the position ofthe mouth and nostrils.ENDOTRACHEAL INTUBATIONFIG.9.17 Commercially available malleable face mask.pharynx. Variations in face shape are not so troublesomein large animals and face masks for horsesand cattle can be made from rigid material with asoft cushion to provide an air-tight seal with themuzzle, but again a variety of sizes is needed.Whenever a face mask is used care must betaken not to cause damage to the eyes and, inspecies of animal that breathe through the noserather than the mouth, it is most important toFIG.9.18 Modification of commercially available facemasks for cats and small brachycephalic dogs to reduceexcessive deadspace.The masks are cut in two and thesmaller diameter cemented inside the other.Thistelescoping produces a more rigid mask with a muchsmaller deadspace.The history of endotracheal intubation in animalsis older than that of anaesthesia. In 1542 Vesaliuspassed a tube into the trachea of an animal andinflated the lungs by means of a bellows to keepthe animal alive while the anatomy of its thoraciccavity was demonstrated. Similar demonstrationswere given before the Fellows of the Royal Societyin London by Robert Hook in 1667.There are two methods by which inhalationanaesthetics can be administered through an endotrachealtube. The first to be used was that of‘insufflation’ in which the anaesthetics are blowninto the lungs near to the carina through a narrowbore tube. Respiration and the return flow of gasesand vapours takes place around the tube. Theinsufflation technique is said to render respiratorymovements unnecessary but has the great disadvantageof causing a considerable loss of heat andwater vapour from the body. It has fallen intodisuse but has given rise to the technique of intermittententrainment of air to produce ventilationof the lungs of apnoeic small animal patients duringrigid-tube bronchoscopy (Fig. 9.19).A fine-bore tube (usually an 18 s.w.g. needle)mounted at the eyepiece end of a rigid bronchoscopehas oxygen or a mixture of oxygen, nitrousoxide and/or a volatile agent blown through itintermittently. The jet of gas entrains air and generatesenough pressure to inflate the animal’slungs which deflate as soon as the gas flowthrough the fine-bore tube is stopped. To-and-frorespiration takes place through one large-boretube.The standard endotracheal tubes used in manin the UK were designed by Magill and hence areknown as ‘Magill tubes’. Both ‘oral’ and ‘nasal’ areavailable. The oral tubes have comparatively thickwalls and are intended for intubation through themouth, while the ‘nasal’ tubes, designed for passagethrough the nostril into the trachea, havecomparatively thin walls. The tubes are obtainable

220 PRINCIPLES AND PROCEDURESFIG.9.19 Entrainer on rigid bronchoscope to allow ventilation of the lungs of the apnoeic patient during bronchoscopy.in red rubber (seldom encountered today), plastic,or silicone rubber. The oral tubes may be eitherplain, or fitted with a cuff which can be inflatedwith air after the tube has been passed into the trachea.The inflated cuff provides an airtight sealbetween the wall of the trachea and the tube sothat all respired gases must pass through thelumen of the tube. A good seal between the tracheaand cuff reduces the danger of inhalation of foreignmaterial, but over inflation must be avoidedbecause this may result in either pressure damageto the mucous membrane of the trachea or torespiratory obstruction by pressing the wall of thetube into its lumen (Fig. 9.20).Some of these problems may be overcome bythe use of tubes which have a high volume, lowpressure cuff but these tubes may be difficult topass through the larynx. On all cuffed tubes a pilotballoon gives some guidance to the degree of inflationbut does not show when an air-tight seal hasbeen obtained. The cuff should be inflated with airuntil gentle compression of the reservoir gag of theanaesthetic circuit to which the patient is connectedno longer causes an audible leak of gasaround the tube.Intracuff and ‘leak-past’ pressures of varioustypes of tube have been measured and it has beenshown that air diffuses out of the cuff irrespectiveof the material being red rubber, later or PVC. Thematerial of the cuff stretches under stress, increasingcuff volume. The ‘leak-past’ pressure decreaseswith red rubber and silicone rubber tubes butincreases with PVC tubes as time passes. Pressurechanges within the cuff may be caused by the dif-FIG.9.20 Radiograph showing occlusion of anendotracheal tube due to over-distension of the inflatablecuff.

ANAESTHETIC ADMINISTRATION 221fusion of gases – the most important gas is oxygenand when the respired gases contain 30% oxygenthe pressure in the cuff can increase by up to90mmHg (0.9KPa). Ideally, the pressure inside thecuff should be monitored to prevent damage to thetracheal mucosa but in practice this is seldomdone.Length of endotracheal tubesAn endotracheal tube which is too long may beinadvertently introduced into one or the other ofthe main bronchi; this results in one lung providinga large ‘shunt’. Most commonly the tube willenter the right main bronchus. Endobronchialintubation may give rise to persistent cyanosis andhypercapnia. It should be suspected if an animalshows cyanosis when breathing an oxygen-richmixture through an endotracheal tube. Often veryhigh inspired concentrations of volatile anaestheticagent are required to keep the animal asleep.All new Magill tubes must be cut to the correctlength both to ensure that endobronchial intubationis impossible and to minimize the respiratorydeadspace. They should be cut so that when theirbevelled tip lies between the larynx and carinatheir cut end is immediately beyond the nostrils.Also, the connecting piece between the tube andanaesthetic delivery apparatus should be as shortas possible. Unfortunately with many moderntubes, the tube through which the cuff is inflated isenclosed within the wall of the endotracheal tube,making it impossible to shorten.Reinforced endotracheal tubesFrequent use with associated cleaning and sterilizationprocesses makes red rubber endotrachealtubes soft and plastic tubes may soften whenwarmed to body temperature. Soft tubes flattenout and are easily compressed by pressure.Obliteration of the lumen from either of thesecauses may give rise to serious obstruction of theairway. Patency of the airway, when the animal hasto be placed in any position which may cause flatteningor kinking of the tube, can be assured by theuse of an armoured, or reinforced, endotrachealtube. These special tubes incorporate a wire ornylon spiral in their walls. They are more expensivethan the standard tubes, and because there arenot many occasions when their use is essential,many veterinary anaesthetists consider their purchaseto be unjustified. They have thicker wallsthan non-reinforced tubes and are difficult to cut toshorter lengths (they come with a non-reinforcedend to ease their connection to the endotrachealconnector). They are usually very flexible and tofacilitate their introduction it is often necessary tostiffen them with a malleable stilette introducedinto their lumen in such a way as not to protrudefrom the bevelled tip.LARYNGOSCOPESAlthough not strictly essential, a laryngoscopegreatly facilitates the process of intubation inmany animals and is a piece of equipment which ismost desirable. A suitable laryngoscope usuallyholds a dry electric battery in the handle and hasdetachable blades of different sizes. The bladesshould be designed so as to enable the passage of alarge bore endotracheal tube to be made as easilyas possible. For veterinary purposes one standardhuman adult and one child size ‘Magill pattern’blades and one special blade are the minimumrequirements. The special blade should be of theMacintosh pattern, 3/4 inch (1.9 cm) wide, and23 to 30 cm long. The blades should be separatefrom the lamp and its electrical connections so theycan be sterilized by boiling without risk of damageto the electrical system. Various types are availableand one suitable instrument is shown in Fig.9.21.For small animal use, a modified penlight torchcan provide an inexpensive light source which,although less satisfactory than a laryngoscope,may prove adequate in an emergency. For largeanimals, special laryngoscope blades are requiredand the Rowson blade (Rowson, 1965) has greatlysimplified the intubation of small cattle, sheep andlarge pigs. The most attractive feature of theRowson blade is that it makes lifting of the lowerjaw to expose the laryngeal opening unnecessary.The 14 inch Wisconsin blade is excellent for Ilamas,large rams and goats and in these animals it maybe necessary to use an introducer in the form of astilette passed through the tube to stiffen it.Difficult intubation may be overcome by use of afibrescope to identify the glottis. Before passing the

222 PRINCIPLES AND PROCEDURESCLEANING AND STERILIZATION OFANAESTHETIC EQUIPMENTFIG.9.21 Laryngoscope with detachable Macintoshblade – a wide variety of patterns of blade areavailable.fibrescope it is introduced through an appropriatesized endotracheal tube so that this tube may be‘railroaded’ into the trachea once the tip of thefibrescope is seen to be correctly placed. Becausethe fibrescope occupies most of the lumen of thetube it must be quickly withdrawn leaving the tubein place. Intubating flexible endoscopes (KeyMed,KeyMed House, Stock Road, Southend-on-Sea,Essex SS2 5QH) are manufactured with tougherrubber than is used in other flexible endoscopes toensure that ‘railroading’ an endotracheal tube willnot cause deterioration of the endoscope.Wide-bore tubes may be introduced into the tracheain various ways and the method to be adoptedin any particular case is decided by the skill andexperience of the anaesthetist and the kind of animal.In the chapters dealing with anaesthesia forthe various species of animal will be found descriptionsof techniques which undergraduate studentsand anaesthetists in training have foundrelatively easy to master. Experienced, skilledanaesthetists should of course be able to pass anendotracheal tube in all species of animal underany circumstances and most develop their owntechniques.Anaesthetic equipment is obviously a potentialsource of cross infection from one patient to thenext; ideally, all parts of the breathing systemsshould be capable of being sterilized between eachuse. Unfortunately, this is not very practical asparts of the apparatus do not tolerate many of thepossible methods of sterilization and, where theydo, most of the methods shorten their life. Thenearer the part of the system to the patient, thegreater the risk of cross infection from organismsassociated with previous usage. The compromiseusually adopted with anaesthetic equipment is,therefore, to sterilize the components such asendotracheal tubes or face masks after use, whilstthe rest of the equipment is only regularly cleanedby washing. All equipment should, however, besterilized periodically, or immediately followingits use on a patient thought or known to be sufferingfrom an infectious disease.Whatever method of sterilization is to beemployed, the apparatus must first be thoroughlycleaned by washing in hot water with a detergentor soap. Many parts of the breathing circuit may bedamaged if subjected to autoclaving. Heat sterilizationby boiling may be used for endotrachealtubes although regular treatment of this naturedoes shorten their life. The various means of chemicalsterilization rarely damage equipment butwhen they are used the apparatus must be thoroughlywashed afterwards because traces ofchemical, particularly if remaining on face masksor endotracheal tubes, may prove to be very irritantindeed to the next patient The use of ethyleneoxide gas is now a practical method of sterilizationin veterinary practice and although it causes nodamage to anaesthetic equipment a sufficient time(up to 7 days) must be allowed to elapse before theequipment is used again in order to allow all tracesof this most irritant gas to disappear. Also, it mustbe remembered that some plastics which havebeen previously sterilized by γ irradiation (e.g.most plastic endotracheal tubes supplied in sterilepackets) produce an extreme toxic substance, ethylenechlorohydrin, when subjected to ethyleneoxide gas so they should never be resterilized byexposure to the agent (Dorsch & Dorsch, 1975).

ANAESTHETIC ADMINISTRATION 223REFERENCESClutton, R.E. (1995) The right anaesthetic breathingsystem for you? In Practice 5: 229–237.Dorsch, J.A. and Dorsch, S.E. (1975) UnderstandingAnaesthetic Equipment. Baltimore: Williams andWilkins.Humphrey, D. (1983) A new anaesthetic breathingsystem combining Mapleson A.D and E principles.A simple apparatus for low flow universal usewithout carbon dioxide absorption. Anaesthesia38: 361–372.Hunt, K.H. (1955) Resistance in respiratory valves andcanisters. Anesthesiology 16: 190–205.Kain, M.K. and Nunn, J.F. (1968) Fresh gaseconomics of the Magill circuit. Anesthesiology29: 964–974.Laredo, F.G., Sanchez-Valverde, M.A., Cantalapiedra,A.G., Pereira, J.L. and Agut, A. (1998) Efficacy ofthe Komesaroff anaesthetic machine fordelivering isoflurane to dogs. Veterinary Record143: 437–440.Lilja, A.S., Alibhai, H.I.K. and Clarke, K.W. (1999)Evaluation of the Humphrey ADE circuit duringspontaneous ventilation in dogs. Journal of VeterinaryAnaesthesia (in press).Mapleson, W.W. (1954) The elimination of rebreathing invarious semi-closed anaesthetic systems. BritishJournal of Anaesthesia 26: 323–332.Miller (1995) An enclosed efferent afferent reservoirsystem: the Maxima. Anaesthesia and Intensive Care.23: 292–295.Moens, Y. (1985) Introduction to the quantitativepractice and the use of closed circuit in veterinaryanaesthesia. Proceedings of the 2nd InternationalCongress of Veterinary Anesthesia, Sacramento, p.57.Muir, W.W. and Gadawski, J. (1998) Cardiorespiratoryeffects of low-flow and closed circuit inhalationanesthesia using sevoflurane delivered with anin-circle vaporizer, and concentrations of compoundA. American Journal of Veterinary Research 59: 603.Rowson, L.E.A. (1965) Endotracheal intubation in thepig. Veterinary Record 77: 1465.Sykes, M.K. (1968) Rebreathing circuits. British Journal ofAnaesthesia 40: 666–670.Waterman, A.E. (1985) Clinical experiences with theKomesaroff machine. Journal of the Association ofVeterinary Anaesthetists 13: 42–49.Waterman, A.E. (1986) Clinical evaluation of theLack coaxial breathing circuit in small animalanaesthesia. Journal of small Animal Practice 27:591–598.

General principles of local10analgesiaINTRODUCTIONMany surgical procedures can be satisfactorilyperformed under local analgesia. Whether or notsedation is employed as an adjunct will depend onthe species, temperament and health of the animal,as well as the magnitude of the procedure. In adultcattle and horses, many operations can be performedon standing animals and since sedationmay induce the animal to lie down, it is oftenbetter avoided. In other animals sedation shouldbe adopted since efficient surgery is greatly facilitatedby the reduction of fear and liability to suddenmovement. Local analgesics may exert asedative action when they are absorbed from sitesof injection and for surgery on the standing animalthe dose of any calming sedative drug must bereduced to allow for this.There are several features of local analgesiawhich render it particularly useful in veterinarypractice. It enables protracted operations to be performedon standing animals and in large animalsthis avoids the dangers associated with prolongedrecumbency. Local analgesia can also be a usefultechnique to reduce the depth of anaesthesia neededfor major surgery during general anaesthesia. Afeature which appeals to those in general veterinarypractice is that the surgeon can induce localanalgesia and operate without the assistance of ananaesthetist. The techniques of local analgesia arenot difficult to learn and do not involve the use ofexpensive or complicated equipment.ANATOMY AND FUNCTION OF THENERVE FIBREThe unit of nervous tissue consists of the nerve celland its processes, the dendrites and the axon. Theprocesses are dependent upon the intact connectionwith the nerve cell for survival and nutrition.Conventional theories of nerve function have longbeen based on the assumption that the surfacemembrane of nerve fibres and cells exists as a differentiallypermeable interface between tissuefluid and the liquid phase of the neuronal cytoplasm.However, modern cytological studies renderit very unlikely that external surfaces of nervecells and fibres are bathed directly by tissue fluid,for it now appears that most neurones are entirely,or almost entirely, covered by supporting cellsapplied directly to their external surfaces. Thus,the diffusion barrier surrounding neurones mustbe considered to involve these supporting cellsand their membranes. The larger nerve cells aresurrounded by a coat of fatty material – the myelinsheath. The thickness of this sheath increases withthe diameter of the axon it encloses, and it is composedof a number of lipoprotein lamellae which,in the case of peripheral nerve fibres, are laid downfrom the Schwann cells that enclose the axons. Themyelin lamellae are not continuous along theentire length of the fibre, being interrupted at moreor less regular intervals (the nodes of Ranvier) toleave short segments of the axon covered by the225

226 PRINCIPLES AND PROCEDURESTABLE 10.1 Relationship between nerve fibresize and function.The divisions are not absoluteand there is a varying degree of overlap fromone diameter group to the otherGroup Fibre diameter Functionsrange (µm)I 15–25 Somatic motor efferents(myelinated) Proprioceptive afferentsII 5–15 Cutancous afferents(myelinated) (except pain)2–5 Pain efferents(myelinated) γmotor efferentsIII

LOCAL ANALGESIA 227concentrations of the drug can decrease the exit ofpotassium ions this is irrelevant to the local blockingaction which can occur without any change inresting potential.CLINICALLY USEFUL LOCALANALGESIC DRUGSBASIC STRUCTUREClinically useful local analgesics have a commonchemical pattern of aromatic group–intermediatechain–amine group (Table 10.2). The aromaticgroup confers lipophilic properties while theamine group is hydrophilic. The intermediatechain is usually either an ester or an amide. Theester linkage can be hydrolyzed by esterases, whilethe amide group can only be broken down by liverenzymes. Some compounds lack the hydrophilictail (e.g. benzocaine) and are nearly insoluble inwater so that they are unsuitable for injection butthey can be applied to mucosal surfaces.Modification of the chemical structure altersactivity and the physical properties of the molecule.Lengthening of the intermediate chain oraddition of carbon atoms to the aromatic or aminegroups results in an increase in potency up to a certainmaximum, beyond which any further increasein molecular weight is followed by a decrease inactivity. The addition of a butyl group to the aromaticend of the procaine molecule increases lipidsolubility and gives a 10-fold increase in proteinbinding with an increased duration of action andsystemic toxicity. Similarly, the substitution of abutyl group for the methyl group of the amine ofmepivacaine gives greater potency and a moreprolonged duration of activity. Once again there isan increase in lipid solubility and a greater degreeof protein binding.CocaineCocaine is an alkaloid obtained from the leaves ofErythroxylum coca, a South American plant. It wasfirst introduced into surgery by Koller in 1884,some 38 years after the introduction of generalanaesthesia. Its toxicity and addictive properties inman led to a search for synthetic substitutes andreference to it now has become largely historicalfor it has been almost entirely replaced by compoundswhich do not suffer from these disadvantagesto the same extent. Its one remaining use is forsurgery in the nasal chambers, where its propertyof producing intense vasoconstriction shrinks themucous membrane, allowing more room for thesurgeon and aiding haemostasis.ProcaineProcaine was introduced in 1905 under thetrade name of Novocain, and largely replacedcocaine as a local analgesic. Compared to cocaineits power of penetration of mucous membranes ispoor and following injection nerve block is slow inonset.AmethocaineAmethocaine is a member of the procaine series ofcompounds which is particularly useful for desensitizingmucous membranes. A 1% solution is usedfor instillation into the conjunctival sac instead ofproxymetacaine and a 2% solution is used forthe pharyngeal, laryngeal and nasal mucousmembranes.CinchocaineThis was first introduced as Percaine in 1929. It isknown as ‘Nupercaine’, a name which preventsconfusion with procaine, and in the United Statesas ‘Dibucaine’. The drug is quite different fromeither cocaine or procaine, being a quinoline derivative– butyloxycinchoninic acid diethyl ethylenediamide. It is readily soluble in water and solutionsmay be boiled repeatedly for sterilization. Itis decomposed by alkali, and for this reason tracesof acid are added to solutions which are to bestored. For the same reason Nupercaine mustalways be kept in alkali-free glass containers. Thedrug is much more toxic than procaine, but this iscounterbalanced by the smaller quantities used,for the minimal effective concentration is aboutone-fortieth that of procaine. In addition, the analgesiait produces lasts for very much longer.Nupercaine has been used for every type of localanalgesia but has been found most useful for surfaceand spinal analgesia.

228 PRINCIPLES AND PROCEDURESChemical structures and properties of some commonly used local analgesicsChemical structureAromaticendIntermediatechainAminoendLipidsolubilityAnaestheticdurationOnsettimeAmino estersProcaineH 2 N –C 2 H 5COOCH 2 CH 2 – NC 2 H 51ShortSlowCL2-Chloroprocaine H 2 NH 9 C 4TetracaineNHAmino amidesLignocainePrilocaineEtidocaineMepivacaineBupivacaineCH 3C 4 H 9C 2 H 5COOCH 2 CH 2 – NC 2 H 5CH 3COOCH 2 CH 2 – NCH 3CH 3C 2 H 5NHCOCH 2 – NC 2 H 5CH 3CH 3C 3 H 7NHCOCH – NHCH 3CH3C 2 H 5NHCOCH NC 3 H 7CH 3C 2 H 5CH 3NHCONCH 3CH 3CH 3NHCON18041.5140130ShortLongModerateModerateLongModerateLongFastSlowFastFastFastFastModerate

LOCAL ANALGESIA 229Lignocaine (lidocaine)Since its introduction into veterinary clinicalpractice in 1944 lignocaine (lidocaine in NorthAmerica) has replaced procaine and most othercompounds in every field where local analgesiais used (except for postoperative analgesia).Chemically, lignocaine is N-diethylaminoacetyl-2,6-xylidine hydrochloride and as it is not an esterit is unaffected by pseudocholinesterase (procaineesterase). It is extremely stable in solution andsolutions can be stored and resterilized almostindefinitely, without fear of toxic changes or loss ofpotency. Compared with procaine, lignocaine hasa far shorter period of onset, a more intense and alonger duration of action. Spread through the tissuesis much greater with lignocaine than withprocaine, and injections made in the neighbourhoodof a nerve trunk penetrate more effectively.This facility for tissue penetration has some importantpractical applications. It is unnecessary to addhyaluronidase to solutions of lignocaine for infiltrationor nerve blocking purposes (as is oftenrecommended with other agents) since the spreadingpower of this agent is already adequate.Probably as another result of its tissue penetratingproperties, lignocaine also has marked local analgesicactivity when applied to the surface ofmucous membranes or the cornea. Its activity onmucous membranes is similar to that of cocaine,while on the cornea a 4% solution of lignocaine isapproximately equivalent to a 2% solution ofcocaine.The drug is rapidly absorbed from tissues andmucous surfaces. In dogs, after subcutaneous orintramuscular injection, the blood concentration oflignocaine reaches a maximum in about 30 minutes.The addition of adrenaline (epinephrine) tothe injected solution approximately doubles thetime required for complete absorption. Ten percentor less of an injected dose of lignocaine is excretedunchanged in the urine and the metabolism of lignocainehas, therefore, been the subject of muchinvestigation. Liver is the only tissue which hasbeen shown to metabolize lignocaine in significantquantities. The approximate maximum dose byinfiltration before toxic signs become apparent isnot known with any certainty but is thought to be6–10 mg/kg.PrilocaineThis substance is closely related to lignocaineand possesses the same pKa and onset timeof the block in isolated nerves. However, invivo, prilocaine nerve blocks do not develop asrapidly as lignocaine blocks. It is popular inequine surgery because it is claimed to produceless tissue reaction than lignocaine. It is the mostrapidly metabolized amide and its metabolismreleases o-toluidine, which causes methaemoglobinaemia.MepivacaineThis compound (Carbocaine) closely resembleslignocaine hydrochloride but is slightly less toxic.It has been found to be especially useful for thenerve blocks used in the diagnosis of equine lamenessbecause there is less post-injection oedemathan with lignocaine.BupivacaineBupivacaine (Marcain) is dl-l-butyl-2’.6’-pipecoloxylididehydrochloride, a remarkably stablecompound which is resistant to boiling withstrong acid or alkali and shows no change onrepeated autoclaving. It possesses, to greater orlesser degrees, the most desirable general propertiesof a local analgesic drug.The local analgesic effect of bupivacaine isslower in rate of onset and similar in depth to thatof lignocaine and mepivacaine, but is of muchlonger duration. The addition of adrenaline in lowconcentrations has been shown to increase boththe speed of onset and the duration of analgesia sothat all solutions of bupivacaine for clinical useshould contain adrenaline.Bupivacaine is approximately four times aspotent as lignocaine; hence a 0.5% solution isequivalent in nerve-blocking activity to a 2% solutionof lignocaine. It is generally agreed that bupivacaineprovides a period of analgesia at leasttwice as long as that of lignocaine, and that it isexceptionally well tolerated by all tissues. Due tothese properties it is increasingly used today as acomponent of regimens providing postoperativeanalgesia.

230 PRINCIPLES AND PROCEDURESRopivacaineRopivacaine, a relatively new long acting amidetypelocal analgesic, is the (S) enantiomer of achain-shortened homologue of bupivacaine. Itappears to provide a greater margin of safety thanbupivacaine when used in equal dosage (Reiz etal., 1989). It is an effective long acting drug whengiven epidurally and it appears to be a vasoconstrictorover a wide range of concentrations.Subcutaneous infiltration of plain ropivacaine producescutaneous vasoconstriction equivalent toadrenaline, in contrast to bupivacaine, which producesvasodilatation.PHARMACOKINETICS OF LOCALANALGESIC DRUGSThe concentration of local analgesics in the bloodis determined by the rate of absorption from thesite of injection or application, the rate of tissuedistribution and the rate of metabolism and excretionof the particular compound. The physiologicaldisposition and resultant blood concentrationwill also depend on the age of the animal, its cardiovascularstatus and hepatic function.ABSORPTIONFactors which influence systemic absorption andpotential toxicity of local analgesics are:1. The site of injection2. The dosage3. The addition of a vasoconstrictor4. The pharmacological profile of the agentitself.Multiple injections (e.g. intercostal nerve blocks)may expose the agent to a great vascular area,resulting in a faster rate of absorption. The samedose of agent injected in one site results in a muchlower maximum blood level. Topical applicationof local analgesics at various sites also results indifferences in absorption and toxicity. In general,absorption occurs most rapidly after intratrachealspray for the agent is dispersed over a wide surfacearea, promoting vascular absorption. The rateof absorption is less after intranasal instillationand administration into the urethra and urinarybladder. Peak blood levels occur 10 minutes afterintrapleural instillation. The use of ointments orgels to apply local analgesic drugs to mucousmembranes tends to delay absorption.The absorption and subsequent blood levels oflocal analgesics is related to the total dose of drugadministered regardless of the site or route ofadministration. For most agents there is a linearrelationship between the amount of drug givenand the resultant peak blood level. Local analgesicsolutions frequently contain a vasoconstrictor,usually adrenaline (epinephrine), in concentrationsvarying from 5 µg/ml to 20 µg/ml, to delaythe absorption and prolong the action of the agent.Although other vasoconstrictors such as noradrenaline(norepinephrine) and phenylephrine havebeen employed with local analgesic drugs neitherseems as effective as adrenaline in a concentrationof 1:200 000.The pharmacological characteristics of the specificlocal analgesic also influence the rate anddegree of vascular absorption. For example, lignocaineand mepivacaine are absorbed more rapidlythan prilocaine from the epidural space, whilebupivacaine is absorbed more rapidly than etidocaine.These differences are probably a reflection ofdifferences in both vasodilator activity and lipidsolubility.Local analgesic drugs distribute themselvesthroughout the total body water. Their rate of disappearancefrom the blood (tissue redistribution),the volume of distribution and relative uptake bythe various tissues are related to their physiochemicalproperties. The distribution can be describedby a two or three compartment model. The rapiddisappearance (α) phase is believed to be related touptake by rapidly equilibrating tissues (i.e. thosewith high vascular perfusion). The slower β phaseof disappearance from blood is mainly a functionof distribution to slowly equilibrating tissues andthe metabolism and excretion of the compound.This secondary phase may also be subdivided intodistribution into slowly perfused tissues (true βphase) and a phase of metabolism and excretion (γphase). A comparison of the three amide drugs(lignocaine, mepivacaine and prilocaine) revealsthat prilocaine is redistributed at a significantlyfaster rate from blood to tissues than is lignocaine

LOCAL ANALGESIA 231or mepivacaine (which have similar rates of tissueredistribution). In addition, the β disappearancephase from blood also occurs more rapidlywith prilocaine, suggesting a more rapid rate ofmetabolism.Local analgesics become distributed throughoutall body tissues, but the relative concentrationin different tissues varies. In general the morehighly perfused organs show a greater concentrationof local analgesic drugs than less well perfusedorgans. The highest fraction of an injecteddose is found in the skeletal muscles since theirmass makes them the largest reservoir but theyhave no specific affinity for these drugs.The pattern of metabolism of the local analgesicsvaries according to their chemical composition.Plasma pseudocholinesterase hydrolyses theester class agents. Chloroprocaine is hydrolysedmore rapidly than procaine or tetracaine and thetoxicity of these agents is directly related to theirrate of degradation. Less than 2% of unchangedprocaine is found in the urine but 90% of paraaminobenzoicacid, its primary metabolite, isexcreted in urine. The amide class of local analgesicsundergoes enzymatic degradation primarilyin the liver. The rate of hepatic degradationmay vary between compounds which, in turn,may influence the toxicity of the specific agent.Prilocaine undergoes the fastest rate of enzymaticmetabolism and is the least toxic of the amide-typeagents. Lignocaine is metabolized more rapidlythan is mepivacaine. Some degradation of theseamide compounds may take place in tissues otherthan liver cells and their metabolism is more complexthan that of the ester compounds. Themetabolites of local analgesics are of clinicalimportance since they may exert both pharmacologicaland toxicological effects similar to those oftheir parent compounds.The excretion of amide-type compounds occursthrough the kidneys. Less than about 5% of thedrug is excreted unchanged. The major fractionappears in the form of various metabolites, someas yet unidentified. The renal clearance of theamide-type drugs appears to be inversely relatedto their protein binding abilities. Renal clearance isalso inversely proportional to urinary pH, suggestingthat urinary excretion occurs by non-ionicdiffusion.In animals with a pathologically low hepaticblood flow, or advanced hepatic disease, significantlyhigher blood concentrations of the amideagents may be expected. This is important for thedisappearance of lignocaine from the blood maybe markedly prolonged in animals with congestiveheart failure.SYSTEMIC AND TOXIC EFFECTS OFLOCAL ANALGESIC DRUGSLocal analgesics affect not only the nerve fibres butall types of excitable tissue including skeletal,smooth and cardiac muscle. Side effects occurwhen they enter the systemic circulation and themost severe follow inadvertent intravascular injection,but absorption from tissue depots can also beresponsible if the rate of absorption exceeds therate of metabolism or elimination from the body asit may be if the dose rate is too high. Cardiovascular,respiratory and central nervous disturbancesare common side effects but allergicreactions occasionally occur with ester-typeagents.CENTRAL NERVOUS SYSTEMLocal analgesics have a complex effect on the centralnervous system. Usually, sedation is the firstobvious sign but a further increase in the brainconcentration produces grand mal tonic-clonicseizures. One explanation given for this is thatlocal analgesics stabilize cell membranes even atlow concentrations but as the concentrationincreases more and more of the cells havinginhibitory functions are affected and as theinhibitory pathways become blocked facilitatoryneurones are released to act unopposed, thus givingrise to excitation and convulsions. As the concentrationof the drug in the brain rises still higher,however, depression of both inhibitory and facilitatorysystems occurs with overall loss of centralnervous activity. For this explanation to be valid itwould seem that there must be certain predilectionsites of activity in the brain but evidence for theirprecise location is conflicting.Lignocaine and other agents have anticonvulsantactivity as well as the ability to produce

232 PRINCIPLES AND PROCEDURESseizures. In general, the dose giving rise to anticonvulsantactivity is less than that associated withconvulsions and a marked antiepileptic effect isobserved. It seems probable that this antiepilepticactivity is due to depression of specific hyperexcitablecortical neurones.Seizures induced by local analgesics may bemanaged in several different ways but it should beremembered that many are self-limiting due to therapid redistrubution of the drug from the brain toother tissues. Grand mal seizures increase the cerebraloxygen consumption yet interfere with normalpulmonary function, while hypercapniapotentiates the effect of local analgesics on thebrain. Thus, whatever else is done, measures toprotect the airway and ensure adequate alveolarventilation must be taken immediately. If theseizures continue for more than 1–2 minutesdiazepam (up to 0.2 mg/kg) or 5 mg/kg ofthiopental should be given by i.v. injection. It hasbeen suggested that diazepam has a specific antagonisteffect against the excitatory effects of localanalgesics on the limbic brain and that it gives riseto fewer side effects than thiopental, but the barbituratehas a shorter duration of action and in manysituations this short duration of action may bedesirable.The stimulant action of local analgesics on thebrain has led to their abuse by human subjectsseeking to achieve the preseizive aura withoutusing sufficient of the drug to produce a generalizedseizure, and also in the horse racing industrywhere they have been given to enhance performance.CARDIOVASCULAR SYSTEMLocal analgesics have both direct and indirecteffects on the cardiovascular system. In experimentson isolated cardiac muscle preparationswith concentrations of lignocaine known to controlarrythmias but which are not toxic, it has beenshown that automaticity is strongly suppressed.The duration of the action potential and effectiverefractory period is shortened in both Purkinjefibres and ventricular muscle and it has been suggestedthat these effects are responsible for the stabilizingaction which lignocaine has on cardiacirregularities. Toxic concentrations of lignocaineare associated with a decrease in the maximumrate of depolarization on Purkinje fibres and ventricularmuscle, a reduction in amplitude of theaction potential, and a marked decrease in conductionvelocity. On the ECG there is an increase in theP–R interval and in duration of the QRS complex.Sinus bradycardia may proceed to cardiac arrest athigh lignocaine concentrations. At concentrationsof lignocaine sufficient to control arrythmias thereis no reduction in cardiac output or myocardialcontractility. Lignocaine is particularly useful forcontrolling ventricular arrhythmias perhapsbecause it enhances the efflux of K + from ventricularmuscle and Purkinje fibres but not from atrialtissue.The usual clinical doses of lignocaine and otheranalgesics used for local and regional analgesia donot give rise to blood levels which are associatedwith cardiodepressant effects. Accidental intravascularinjection of excessive doses may, however,give rise to concentrations which result in significantdecreases in myocardial contractility or evencardiac arrest.Cocaine is the only agent which produces vasoconstrictionand it is believed that this results fromuptake of catecholamines into tissue binding sites.Most other agents have a dose-related effect; lowconcentrations stimulate smooth muscle producingvasoconstriction, while high concentrationscause vasodilatation.Secondary effects independent of the directactions of whatever agent is used can occur due tothe regional nature of the block produced.Systemic hypotension may accompany epiduralinjection due to sympathetic blockade. For theheart rate to be able to compensate for falls in arterialpressure the cardioaccelerator fibres in the firsttwo thoracic nerves must be unaffected and if theblock reaches this level vasodilatation will occur inthe forelimbs and peripheral resistance willdecrease so that hypotension will be very severe. Ifthe block affects the caudal nerves only the hypotensionis less profound because of compensatoryvasoconstriction in the rostral regions of the body.Renal and hepatic blood flow may also decreasesecondary to the effects of the drugs on the centralnervous system and this will result in a decrease inboth renal excretion and liver metabolism of theamide-type drugs.

LOCAL ANALGESIA 233RESPIRATORY SYSTEMAt subtoxic doses bronchial smooth muscle isrelaxed and some respiratory depression mayoccur from central nervous activity.Local toxic effectsLarge doses of local analgesics cause damage totissues such as nerves and skeletal muscles and theuse of excessive amounts together with vasoconstrictorsin wound areas may delay healing.Cytotoxicity is correlated with potency – the morepotent the drug the greater its cytotoxic activity.Methaemoglobinaemia has been reported indogs following topical application of largeamounts of benzocaine for relief of pruritis.Local analgesics must always be treated withrespect and it is important that in practice onlyminimal, accurately placed quantities are used iftoxic effects are to be avoided.INTERACTION WITH OTHER DRUGSThe duration of nerve block can be increased andthe potential risk of systemic toxicity can bereduced by combining vasoconstrictor drugs withlocal analgesics so as to delay absorption from theinjection site. As already mentioned, it is probablethat adrenaline in concentrations between1:100000 and 1:200 000 is the most generally usefuldrug for this purpose. Dilute solutions of adrenalinetend to be unstable and for this reason mostcommercially available solutions of local analgesicscontain rather more – usually about 1:80 000– to allow for deterioration in strength duringshelf-life.Local analgesics can enhance the duration ofaction of both depolarizing and non-depolarizingneuromuscular blocking agents. Drugs such as thephenothiazine derivatives and pethidine maylower the threshold at which the convulsantactions of local analgesics are encountered.FORMS OF LOCAL ANALGESIASURFACE ANALGESIAAgents which cause freezing of the superficial layersof the skin are sometimes used for analgesia.Ice is the simplest but, generally, volatile substanceswhich cause freezing by rapid volatilizationfrom the surface of the skin are used (e.g. ethylchloride spray and carbonic acid snow). Theiraction is very superficial and transient andtheir use is limited to the simplest forms of surgicalinterference, such as the incision of small superficialabscesses. Used too freely, they may causeskin necrosis. In man, the thawing out after theiruse is known to be painful. Decicaine and lignocaineare sometimes incorporated in ointmentsand applied with friction to the skin. Some slightabsorption occurs producing a local numbingwhich has been found to be useful for the controlof pruritis but they have little use in anaesthesia.Similarly, aqueous solutions of 2% lignocaine or4% procaine may be applied topically for the reliefof pain from superficial abraded or eczematousareas.EMLA cream (2.5% lignocaine base with 2.5%prilocaine base) and 4% amethocaine gel can beapplied to the skin over the site of venepuncture torender subsequent penetration by needles andcatheters painless. They are applied under anocclusive dressing and anaesthetizing the superficialskin layers takes about 60 minutes withEMLA cream but less than 30 minutes withamethocaine gel.For analgesia of the mucous membranes of theglans penis and the vulva the application of lignocainein carboxymethylcellulose gel is the preparationof choice. (This gel possesses very goodlubricating properties and is an excellent lubricantfor urethral catheters.)For procedures in the nasal chambers of thehorse, or for the transnasal passage of a stomachtube in dogs, spraying with 4% lignocaine providessatisfactory analgesia. In ophthalmic surgery4% lignocaine is quite safe but the agent of choicefor topical analgesia of the cornea is proxymetacainehydrochloride (2-diethylaminoethyl-3-amino-4 propoxybenzoate hydrochloride), knownby the trade name of ‘Ophthaine’. Using a singledrop, the onset of corneal analgesia occurs inabout 15 seconds and persists for about 15 minutes.This compound does not produce pupillarydilatation and is non-irritant, but its solutionis rather unstable, having a shelf-life of only12 months.

234 PRINCIPLES AND PROCEDURESINTRASYNOVIAL ANALGESIASurface analgesia is also employed for the relief ofpain arising from pathological processes or operationsinvolving joints and tendon sheaths. A solutionof local analgesic is injected into the synovialcavity and then dispersed throughout the cavityby manipulation of the limb. If the synovial cavityis distended with fluid, it is first drained to ensurethe injected solution is not excessively diluted. It isrelatively simple to introduce a needle into synovialsheaths when they are distended with fluid,but entry to a normal sheath is not easy. Whensearching for a synovial sheath the exploring needleshould be connected to a syringe containingthe analgesic solution and a slight pressure maintainedon the syringe plunger. As soon as the needleenters the sheath resistance to injectiondisappears and some of the solution enters thesheath, lifting its wall away from the underlyingtendon. Analgesia develops within 5 to 10 minutesafter successful injection and persists for about onehour depending on the drug employed. The injectionrenders the synovial membrane insensitivebut it is not known whether the nerve endings inthe underlying structures are affected.Intra-articular injection of local analgesics inconnection with the diagnosis of lameness was firstintroduced by Forssell at the Royal VeterinaryCollege, Stockholm in 1921, and his techniques,with only slight modifications, are still in use today.Clearly, almost every joint and tendon sheath in thebody can be treated in this way and the technique isnow being increasingly employed for the relief ofpostoperative pain after arthrotomy.INFILTRATION ANALGESIABy this method the nerve endings are affected atthe actual site of operation. Most minor surgicalprocedures not involving the digits, penis or teatscan be performed under infiltration analgesia andthe technique is also useful, in conjunction withlight narcosis, for major operations in animalswhich are bad operative risks. Infiltration should,however, never be carried out through, or into,infected or inflamed tissues.Suitable concentrations of lignocaine for canineand feline anaesthesia are 0.2 to 0.5%, and strongersolutions than 0.5% should never be necessary. Inlarge animals 2% solutions of lignocaine are commonlyused. Bupivacaine is used in concentrationsof 0.125 to 0.250%. Care must be taken to minimizethe total doses of analgesic in dogs and cats toavoid toxic reactions; maximum effective dilutionof the agent is necessary. It is usual to add adrenaline(1:400 000 to 1:200 000) to the solution, but thisvasoconstrictor should be omitted when thereare circumstances present which may interferewith healing, e.g. damaged tissue, possible contamination.A hypodermic syringe and needle is all theapparatus necessary for the administration of localinfiltration analgesia. The limits of the area to beinfiltrated are conveniently defined and markedfor subsequent recognition by the use of intradermalweals. To produce an intradermal weal a shortneedle is held almost parallel to the skin surfacewith the bevel of its point uppermost. The needleis thrust into the skin until the bevel is no longervisible and by exerting considerable pressure onthe plunger of the syringe 0.5 to 1.0 ml of localanalgesic solution is injected. The resulting weal isinsensitive as soon as it is formed and if puncturesare repeatedly made at the periphery of suchweals, a continuous weal can be produced alongthe proposed line of incision without an animalfeeling more than the initial needle prick. Suchintradermal infiltration is only easily performed inthick-skinned animals; in horses and cattle it isusual to simply mark the proposed line of infiltrationby raising a weal at either end of the line.Subcutaneous tissues are infiltrated by introducinga needle through the skin at the site of anintradermal weal. For infiltration of a straight lineincision a needle about 10 cm long is introducedalmost parallel to the skin surface and pushedthrough the subcutaneous tissue along the proposedline. Before injecting any local analgesicsolution, aspiration is attempted to ascertain thatthe needle point has not entered a blood vessel. Ifblood is aspirated back into the syringe, the needleis partially withdrawn and reinserted in a slightlydifferent direction. About 1 ml of solution is injectedfor every centimetre length of incision as theneedle is withdrawn. If the proposed incision islonger than the needle it may be infiltrated from itsmiddle, the needle being introduced first in one

LOCAL ANALGESIA 235direction and then in the opposite direction. Verylong incisions will necessitate more than one puncture,but the needle may be reinserted throughthe extremity of the area that has already beeninfiltrated so that the animal suffers only thesensation of one needle insertion. Care shouldbe taken to infiltrate an adequate area at the outset,so there is no necessity for further infiltrationas operation proceeds. It is always better to overdolocal infiltration than to apply it inadequatelyand to use more of a dilute rather than less of aconcentrated, solution of local analgesic. Localinfiltration may also be used at the concludingstages of an operation carried out under generalanaesthesia to ensure a measure of postoperativepain relief.To infiltrate several layers of tissue, the procedureis to inject, from one puncture site, firstthe subcutaneous tissue and then, in successionby further advancing the needle, the deepertissues.REGIONAL NERVE BLOCKSOne form of regional nerve block consists of makingwalls of analgesia enclosing the operationfield. It is accomplished by making fanwise injectionsin certain planes of the tissues so as to soak allthe nerves which cross these on their way to theoperation site. Usually the entire thickness of thesoft tissue in which the nerves run is involved. Incattle and sheep, for flank coeliotomy, two linearinfiltrations are made of the whole thickness of theabdominal wall, one cranial to and one dorsal to,the line of incision (Fig. 10.1).Ring block of an extremity is another specialtype of regional analgesia in which a transverseplane through the whole extremity is infiltratedand particular attention is paid to the sites of largenerve trunks. In limbs the technique is more effectivewhen the injection is made distal to a tourniquet.When used for operations on cow’s teats it isimportant that vasoconstrictors should not beadded to the analgesic solutions, for prolongedvasoconstriction may result in ischaemic necrosisof the end of the teat.More commonly, regional analgesia is broughtabout by blocking conduction in the sensory nerveor nerves innervating the operation site. TheIncisionFIG.10.1 The L-block often used for flank coeliotomy incattle and sheep.This technique is effective butcumbersome and,if properly carried out,time consuming.operative field itself is not touched while itssensitivity is abolished and good analgesia resultsfrom the use of small quantities of solution. Thesolution must, however, be brought into the closestpossible contact with the nerve which is to beblocked, and special care must be taken to ensurethat there is no sheet of fascia between the nerveand the site of deposition of the analgesic solutionsince solutions do not diffuse through fascialsheets. Success in regional nerve blocks comesonly from constant practice, as does success inother techniques, but clearly it requires a thoroughknowledge of the topographical anatomy of thenerves and sites of injection. Moreover, no description,however long and detailed, or however wellillustrated, can ever be more than a poor substitutefor demonstration and tuition by an experiencedpractitioner.It is quite beyond the scope of this book to givea complete account of all the nerve blocks that canbe carried out, but in the following chapters varioustechniques will be described, arranged moreor less on a regional basis. Selection presents difficultyin a book of limited scope and must be ratherarbitrary, but two considerations have been bornein mind. First, the methods described are, with oneor two exceptions, comparatively easy to carry outand may be attempted without apprehension.Secondly, they are all useful techniques which aresuitable for inclusion in a general textbook ofanaesthesia.

236 PRINCIPLES AND PROCEDURESINTRAVENOUS REGIONAL ANALGESIA(IVRA)In 1908 Bier reported a technique of ‘venous anaesthesia’and recorded 134 cases, but this techniqueseems to have been largely forgotten until recentyears. After suitable modification it has beenemployed in canine and bovine surgery with gratifyingresults.A small needle or catheter is inserted into a veinat the distal extremity of a limb and temporarilyblocked with an obturator or tap. The limb isexsanguinated, usually with an Esmarch bandage,a tourniquet is inflated or tied to occlude the arterialsupply at the top of the limb and the local analgesicsolution is injected via the needle or catheter.Analgesia of the limb up to the lower limit of thetourniquet comes on rapidly, and when the tourniquetis released it wears off with almost equalrapidity.The mode of action of this technique is unclearbut it seems to be both safe and simple for operationson the digits, especially in ruminant animalsand in dogs unfit for general anaesthesia becauseof a full stomach or intercurrent disease. The goodanalgesia and bloodless field are appreciated bythe surgeon. Analgesia develops distally and progressesproximally so it is important that the injectionis made as distally as possible. If thetourniquet is left in place for more than about1.5 hours ischaemic damage may follow and painis severe. Bupivacaine should not be used for thistechnique because, due to the toxicity of this localanalgesic drug, cardiovascular collapse and deathmay occur when the tourniquet is released. Majoradvantages of this technique is that it requires noprecise knowledge of anatomy and only one injectionneeds to be made.LOCAL ANALGESIA FOR FRACTURESA technique which does not fit readily into anyclassification but must be mentioned, is that oflocal analgesia for the relief of pain arising fromfractured bones. The injection is made directly intothe haematoma at the site of fracture and depositionof the solution in the correct place is essentialfor success. The needle should be inserted as farinto the haematoma and as near the bone ends aspossible. Its position should be verified by aspiration,when blood or blood clot should be drawninto the syringe. Lignocaine hydrochloride (1%solution without adrenaline) is the best agent touse. In small animal patients 2 to 5 ml, and in largeanimals 10 to 15 ml, of solution are required.Analgesia follows 5–10 minutes after injection.Scrupulous asepsis must be observed when injectinginto a fracture site as the consequences of infectionare serious. This technique is particularlysuitable as a first aid measure and in the relief ofpain arising from fractured ribs.SPINAL NERVE BLOCKSSpinal analgesia is a special type of regional blockcomprising the injection into some part of thespinal canal of a local analgesic solution. By cominginto contact with the spinal nerves the drugtemporarily paralyses them and gives rise to lossof sensation in those parts of the body from whichthe sensory portion of the nerves carries impulsesand, when more concentrated solutions are used,paralysis of those parts supplied by the motorfibres. It is divided into two distinct types:1. Subarachnoid injection in which the needlepenetrates the dura mater and the arachnoid materso that the analgesic solution is introduced directlyinto the cerebrospinal fluid.2. Epi- (extra-) dural injection, in which theneedle enters the spinal canal but does notpenetrate the meninges, and the injected solutionpermeates along the spinal canal outside the duramater.In 1885 Corning found that the injection of cocainesolutions into the spinal canal of the dog wasfollowed by paralysis of the hind limbs and lossof sensation in them. This observation receivedvery little attention until 1899 when Bier publishedhis observations in the injection of cocainesolutions into the subarachnoid space in man.In veterinary practice subarachnoid injectionswere first performed in France by Cuille andSendrail in 1901. They demonstrated the methodin the horse, ox and dog, but consequent upon itsperceived difficulties and dangers it was notwidely adopted. Epidural injection was introducedinto the UK by Brook in 1930 and this same

LOCAL ANALGESIA 237worker contributed an extensive review of the subject(Brooke, 1935).Anatomy of the epidural spaceExamination of the epidural space has been performedusing a great number of methods. Postmortemmeasurements, pressure measurementsinvolving needle and catheter introduction intothe space, radiographic examination with or withoutcontrast injection, isotopic studies of localblood circulation, computerized tomography,endoscopic examination, magnetic resonance andcryomicrotome section have all contributed topresent day knowledge of this space but somestudies were, regrettably, unsound. Studies claimingto show the existence of a space by the introductionof air, contrast media or endoscopes, alldisplaced the dura and created the space whichwas then studied. Acceptable studies show thatthe epidural space is not a cavity in the undisturbedstate in vivo; it contains vessels, nerves andfat in dorsal and lateral compartments, i.e. it isonly a potential space.The spinal cord lies within the spinal canal andis covered by three membranes, the dense duramater, the arachnoid mater and the delicate piamater. The wall of the spinal canal is formed by thevertebral arches and bodies, the intervertebraldiscs and the intervertebral ligaments. The tubelikecanal is somewhat flat in the lumbar region.The spinal cord and dura mater end at the lumbarenlargement and the canal itself tapers off caudalto this enlargement to end in the 4th or 5th coccygealvertebra. In each vertebral segment thecanal has lateral openings between the vertebralarches, the ‘intervertebral foraminae’, throughwhich pass blood vessels and the spinal nerves.In the cranial cavity the dura mater is arrangedin two layers, the ‘periosteal’ and ‘investing’ layers,which are firmly adherent except where theysplit to enclose venous sinuses. The outer layerforms the periosteum of the inner surface of thecranial bones and in the spine acts as the periosteumlining the vertebral canal. The investinglayer is continued from the cranium into the spinalcanal but at the foramen magnum is firmly adherentto the margins of the foramen where it blendswith the outer or periosteal layer. Between the twolayers in the spinal canal is the ‘extra-’ or ‘epidural’(perhaps more strictly the ‘interdural’) potentialspace. The dorsal and ventral nerve roots issuingfrom the spinal canal penetrate the investing layerof dura and carry tubular prolongations (duralcuffs) which blend with the perineurium of themixed spinal nerve.The spinal arachnoid mater is a continuation ofthe cerebral arachnoid. An incomplete and inconsistentseptum divides the spinal subarachnoidspace along the midline of the dorsal surface of thecord. In the spinal canal the pia mater is closelyapplied to the cord and extends into the ventralmedian fissure. The blood vessels going to the cordlie in the subarachnoid space before piercing thepia mater. They carry with them into the spinalcord a double sleeve of meninges.Although the venous plexuses of the spinalcanal lie in the epidural space to form a networkthey can be subdivided into:1. A pair of ventral venous plexuses lying oneither side of the dorsal longitudinal ligament ofthe vertebra, into which the basivertebral veinsdrain.2. A single dorsal venous plexus whichconnects with the dorsal external veins. Allinterconnect with one another and form a series ofvenous rings at the level of each vertebra. Theaccidental injection of local analgesic solution intothese veins may occur during the performance ofan epidural block and be responsible for toxicmanifestations.In addition to the venous plexuses, branches fromvertebral, ascending cervical, deep cervical, intercostal,lumbar and iliolumbar arteries enter theintervertebral foramina and anastomose with oneanother, chiefly in the lateral parts of the epiduralspace. The spaces between the nerves, arteries andveins in the epidural space are filled with fatty tissue,the amount of which corresponds with theadiposity of the subject.Each spinal nerve results from the union of tworoots – a dorsal, ganglionic or sensory root and aventral motor root. In the horse, these roots penetratethe dura mater separately and convergetowards the intervertebral foramina where theyjoin, immediately external to the point where thedorsal root has the ganglion placed on it. In the

238 PRINCIPLES AND PROCEDUREScervical, dorsal and cranial lumbar regions thebundles of both roots pass through separate openingsin the dura mater in linear series before unitinginto a root proper, but further caudally thebundles of each root unite within the dura mater.In the dog, union is effected within the intervertebralforamina, except in the lumbar and coccygealregions, where it takes place within the vertebralcanal. The point of fusion of the two roots is ofpractical significance – at any rate, in the small animalsin which epidural anaesthesia is induced. Itis the dorsal root which it is desired to influenceand thus when injecting volumes likely to permeatein front of the cranial lumbar region it is anadvantage to place the animal on its back afterinjection to reduce the extent of the complicatingfactors resulting from paralysis of vasomotorfibres emerging with the ventral root.Spread of epidural analgesiaFor a long time the clinical management of epiduralblockade was based on three assumptionsthat seemed self-evident. First, the number of segmentsblocked would depend on the volume ofsolution injected. The space was considered to be asimple cylindrical reservoir, whose volume wasdetermined by the length and diameter of thecylinder less the volume of the structures it contained.Thus a larger volume would be needed foranimals with long backs than for those with shortones. Secondly, certain escape channels, mostimportantly the intervertebral foramina, drainedthis reservoir and the extent of spread from theinjection site would depend on the leakage of solutionthrough these escape channels. Thirdly, thequality or intensity of sensory and motor blockadewould be governed by the concentration of thelocal analgesic solution used.There were a number of reasons for doubtingthe first two of these assumptions, although thethird gained more credibility from clinical observations.Brook (1935) quoted the assertion of severalpractitioners that, in cattle, the concentrationof the solution employed affected the extent ofthe block. For example, 2–3 ml of 5% lignocaineinjected into the caudal region of a cow blocks asmany segments as 10–12 ml of 2% lignocaine. Thatspread could not be simply governed by volume ofsolution injected was indicated from a well recognizedand commonly used technique for examiningthe bull’s penis. In this technique, if the initialinjection was ineffective succeeding injections ofsmaller volumes of solution seemed to pass cranially,tracking along in the wake of the initial ineffectiveinjection, to extend the neural block andresult in the desired extrusion of the penis from theprepuce. If volume alone was the major determinantof spread, why should this be? The inter-relationshipsof concentration, volume and effect wereindeed difficult to explain on the basis of the prevailingassumptions and it is only in recent yearsthat explanations have been recognized.Other assumptions were also accepted for toomany years. It was held that the dura mater wasimpermeable to the passage of local analgesic (orany other) drugs so that there seemed to be no logicallimit to the volume of solution that could beinjected into the epidural space, and excessiveamounts would leak harmlessly out through theintervertebral foramina. Moreover, since the durafused with the periosteum at the base of the skull,it was assumed that the impermeable dura wouldform a safety barrier preventing the entry of localanalgesics from the epidural space into the intracranialparts of the central nervous system.Unfortunately, neither of these is true. It is nowrecognized that the dura itself appears to be permeableto drugs and it is the pia-arachnoid with itscomplex mixture of water (extracellular fluid andcerebrospinal fluid) and lipid (in cell membranes)which constitutes the permeability barrier(Bernards & Hill, 1990).When a drug is administered into the epiduralspace it must diffuse into neuronal tissue to producean effect. The drug may leak out throughintervertebral foramina, it may get taken up intoepidural fat, it may diffuse into nerve roots beyondthe meningeal sleeves, and it may be removed byepidural blood flow. It may diffuse into the dorsalroots through the dural cuffs or directly throughthe meninges to the cerebrospinal fluid and thespinal cord itself. The site of action of local analgesicsgiven epidurally is still controversial but themain sites are thought to be the nerve roots withinthe dura and nerve tracts in the superficial layersof the spinal cord. The quantity of drug actuallyreaching the neuronal tissues is largely, but not

LOCAL ANALGESIA 239entirely, dependent on the lipid solubility ofthe drug. Hydrophilic drugs easily cross thehydrophilic component of the meningeal tissuebut enter the hydrophobic lipid phase with difficulty,in contrast to hydrophobic drugs.The precise effect of epidurally administeredlocal analgesic drugs is not only related to lipidsolubility, however. Other physiochemical propertiessuch as the pH of the solution, the pKa of thedrug and tissue and protein binding capacity arealso involved. The effectiveness of block is a functionof drug concentration and its durationappears to be related to its protein binding.Although it is the base form of the drug which isresponsible for penetration of the lipid membrane,it is the ionic form which is responsible for blockingsodium channels and so interfering with nerveconduction.It is well recognized that epidural block has atendency to spread widely during pregnancy, atleast at term and when labour has begun. Severalfactors are probably involved. One of the mostimportant is the space occupying and massagingeffects of the distended venous plexuses in theepidural space causing rhythmic pressure waveswhich tend to disperse solutions lying aroundthem. Increased vascularity of the meninges andchanges in the cerebrospinal fluid have also beensuggested as contributing to the spread.In the final analysis it appears that the spread ofsolutions in the epidural space is a function of thetotal mass (concentration × volume) of the particulardrug used, and the site of injection. The durationof block depends on the protein binding of thedrug and whether or not a vasoconstrictor such asadrenaline is mixed with the injected drug.Lignocaine and mepivacaine are less tightlyprotein bound than bupivacaine and ropivacaineand, consequently have a shorter duration ofeffect. The addition of adrenaline prolongs blockdue to lignocaine and mepivcaine but not that ofbupivacaine or ropivacaine (Feldman & Covino,1988).Effects of spinal nerve blocksMany of the spinal nerves which may be involvedin spinal nerve blocks contain fibres of the autonomicnervous system. The function of these nervefibres varies according to the site at which theyleave the spinal cord.The cranial and sacral outflow (parasympathetic)is, in general, concerned with vegetativefunctions such digestion and excretion, whereasthe lumbar and thoracic (sympathetic) outflow ismore closely concerned with protective reflexactivity. Distinct from the sympathetic nervoussystem but running with it are afferent fibres fromthe viscera. These visceral afferent fibres travelwith the postganglionic fibres, but run in the oppositedirection, passing through the ganglia, up thewhite rami and into the dorsal root of the spinalnerve. Their cell bodies are located in the dorsalroot ganglia and an axon passes to a synapse in thelateral horn of the spinal cord. These fibres mustnot be confused with the postganglionic autonomicfibres (vasoconstrictor and vasodilatorfibres) which also follow the dorsal root but whosecell bodies have not yet been precisely located.The postganglionic fibres to a limb mainly passwith the spinal nerves to reach the cutaneousblood vessels, and the sweat and sebaceous glandsin its distal four-fifths. The proximal one-fifth ofthe limb in the groin and axilla is supplied byfibres passing directly from ganglia withoutjoining the spinal nerves. Since the spinal nervealways carries sympathetic fibres, a peripheralnerve block always produces vasodilatation in thedistal part of the limb. Physiologically, neurogenicsympathetic influences are important for the controlof blood pressure by the rapid adjustment offlow resistance and cardiac output on one hand,and by stabilizing the filling of the heart via theireffects on blood distribution on the other.The largest vasomotor nerves in the body arethe splanchnic, which pass to the abdominal viscera.The area supplied by them is so great thattheir paralysis should produce a marked fall inblood pressure. This fall should be most marked inherbivores, in which the abdominal viscera arelarge and their blood supply correspondinglygreat. It would thus seem that when the lumbarand thoracic nerves which give rise to thesplanchnic nerves are blocked a marked fall inblood pressure should occur. However, since thedevelopment of indirect means of measuring arterialpressure it has become apparent that inhealthy subjects this does not happen.

240 PRINCIPLES AND PROCEDURESCardiovascular effects of spinal nerve blocksMost studies to date have shown that changes inarterial pressure, heart rate and cardiac outputvary within ± 20% of pre-block levels, regardless ofwhether the upper analgesic level is above orbelow the T4 spinal segment. This is also true withsegmental epidural blockade, which definitelyeliminates sympathetic drive to the heart, so thatbradycardia during major spinal blocks must be ofvagal origin. Blood flow is always increased in thedenervated extremities (upper and lower limbs)provided the cranial analgesic level exceeds T4. Incontrast, blood flow is decreased in all otherorgans, despite the fact that they are deprived ofneurogenic sympathetic tone. Why the blood flowof the internal organs decreases rather thanincreases is as yet unknown. Alternatives are thatcompared with the limbs, the internal organs havea low resting sympathetic tone, are also under thecontrol of vagal vasoconstrictor tone, respondpreferentially to vasoactive hormones, or theirblood flow decreases when arterial pressure falls.Physiologically, neurogenic sympathetic tone isimportant for the control of arterial blood pressureby the rapid adjustment of flow resistance, the cardiacoutput and stabilization of the filling of theheart via their effects on blood distribution. It isnow apparent, however, that animals can wellmaintain their circulation even when the sympathetictone is removed by autonomic blockade.Spinal nerve blockade jeopardizes primarily thefilling of the heart because of blood pooling in denervatedbody regions, which is normally counteractedby vasoconstriction in the remaininginnervated body regions and particularly by vasoconstrictionin the splanchnic region. Blood loss,low blood volumes from other causes and positiveairway pressure also reduce the filling of the heartwhich must be maintained to avoid circulatorycollapse. The empty heart cannot maintain an efficientcirculation and renders cardiopulmonaryresuscitation ineffective (Keats, 1988).The capacitance vessels – postarteriolar extrathoracicvessels, the venules and veins of thesystemic circulation and the sinusoids of the liverand spleen – contain a large proportion of theblood which can be mobilized in favour of cardiacfilling (Arndt, 1986). Although the pulmonary circulationcontains a large proportion of the totalblood volume it cannot be used actively to increasefilling of the left ventricle because of lack of musclefibres in the blood vessels of greater than about0.2mm in diameter. Consequently left ventricularfilling must passively follow changes in theextrathoracic capacitance vessels.Maintenance of cardiac filling during spinalnerve blockade of sympathetic fibres is dependenton hormonal support systems, particularly vasopressin.(Share 1988). Although angiotensin, themost effective constrictor of resistance vesselsplays a dominant role in normal blood pressureregulation there is evidence that the reninangiotensinmechanism does not respond as ablood pressure support during spinal nerve blocks(Peters et al., 1990). Renin, which controls the formationof angiotensin II, originates from the juxtaglomerularapparatus of the kidneys and isreleased in response to a fall in arterial blood pressure,particularly renal perfusion pressure, butalso and apparently more importantly, in responseto increased sympathetic drive via β 1 adrenoceptors(Ehmke et al., 1987). This drive is eliminatedby spinal nerve blocks which affect the relevantnerve roots. It is, therefore, vasopressin thatstabilizes the arterial pressure during spinalnerve blocks. Vasopressin plasma concentrationsincrease considerably during epidural blocks,especially when combined with severe hypoxaemia.In dogs, when vasopressin is preventedfrom acting by pretreatment with a vasopressin1 receptor antagonist, epidural block causes aprofound fall in blood pressure (Peters et al.,1990a).Site of injectionIt is now customary to classify extradural spinalblocks as epidural and caudal, according to the siteof injection.Caudal blockCaudal injection is made between the coccygealintervertebral spaces with the object of providinganalgesia over the tail and croup as far as the midsacralregion, the anus, vulva, perineum and thecaudal aspect of the thigh. If paralysis of motor

LOCAL ANALGESIA 241fibres is produced the anal sphincter relaxes andthe posterior part of the rectum balloons. Defaecationwill be suspended and stretching of thevulva provokes no response. The vagina dilatesand in animals at parturition ‘straining’ or ‘bearingdown’ ceases while uterine contractions are uninfluenced.Epidural blockEpidural block implies that the injection is madefurther cranially, usually at the lumbosacral junctionor in the lumbar region, although injection issometimes made in the thoracic region. There isusually some degree of interference with the controlof the hind limbs, depending on the drugsused and their concentration. It is important tonote that the motor nerve fibres need not beblocked for this to occur, for block of afferent fibresalone will suffice to destroy temporarily theintegrity of the reflex arcs involved in the maintenanceof muscle tone. Recently there has been considerableinterest, especially in human obstetrics,in using spinal analgesia to provide sensory blockswithout interfering with motor control. The mechanismsbehind this differential blockade are notwell understood but it can be achieved by injectingdilute solutions of the local analgesic into theepidural space. It has been suggested that differentialuptake by nerve fibres firing at differentfrequencies may be responsible since the drugsare taken up more readily by fast firing fibres.An alternative explanation is that it is relatedto the action at the nerve roots – small unmyelinatedC-fibres need to be bathed in solutionfor only a short distance to prevent impulse conduction,whereas in myelinated fibres a longer distanceincorporating several nodes of Ranvier haveto be involved. Bupivacaine at concentrations ofless than 0.125% and ropivacaine at 0.1% appear tohave the least effect on motor fibres while producinggood sensory block.The concept of differential nerve block isattractive in veterinary medicine where it isdesired to avoid recumbency following epiduralanalgesia but it seems that the proprioceptive andsensory deficits produced may limit its application.It will be further discussed in subsequentchapters.Drugs used in epidural injectionsThe efficacy of local analgesic drugs in producingepidural block may be enhanced by mixingthem with other drugs such as opioids, α 2adrenoceptor agonists, NMDA antagonists andnon-steroidal anti-inflammatory drugs. Sincethese drugs have actions which are mostly distinctfrom each other it seems logical that combinationsof different classes of drugs will enhanceanalgesia.OpioidsIn the epidural space there is a synergismbetween local analgesics and opioids (Wang et al.,1993) and combinations are being used clinically atdoses which minimize the side effects of eachindividual drug. The opioids are believed to actat presynaptic sites in the dorsal horn to preventthe release of substance P and on postsynapticreceptors to hyperpolarize nerve cells. Thus,they diminish nociception without having anynoticeable effect on motor function. In rats thepotency of different opioids given intrathecallyhas been shown to be a linear function of lipidsolubility (Dickenson et al., 1990), with decreasingpotency as lipophilicity increases. Morphinehas been the most useful opioid given by epiduralinjection because it has a high potency and along duration of action. It has been used indogs (Bonath & Saleh, 1985), cats (Tung & Yaksh,1982), horses (Valverde et al., 1990), and goats(Pablo, 1993). The common side effects noted inanimals with epidural morphine are pruritis andurinary retention (Drenger & Magora, 1989). It isbelieved that only about 0.3% of epidural morphinecrosses the meninges in dogs (Durant &Yaksh, 1986).Pethidine (meperidine)In cats pethidine given epidurally has a rapidonset of action with a duration of up to 4 hours,depending on the dose (Tung & Yaksh, 1982). Itmust be noted in this connexion that pethidine haslocal analgesic properties in addition to its opioidactivity (Jaffe & Rowe, 1996) and this may have abearing on the rapidity of onset.

242 PRINCIPLES AND PROCEDURESMethadoneIntrathecal methadone increases urinary bladdertone and decreases bladder compliance in dogs(Drenger et al., 1986). It has also been given to cats(Tung & Yaksh, (1982) by epidural injection indoses of 0.7 to 1.0 mg/kg.OxymorphoneEpidural oxymorphone has been given todogs and 0.1 mg/kg was shown to more effectiveand to last longer (10 hours compared with2 hours) than 0.2 mg/kg given i.m. (Popilskis et al.,1991). A more recent clinical study indicatedthat 0.05 mg/kg epidurally gave about 7 hours ofgood analgesia without significant side effects(Vesal et al., 1996).Fentanyl, sufentanilThere is considerable doubt about the effectivenessof these two opioids when given epidurally.ClonidineClonidine has been used quite extensivelyin humans and is known to produce a dosedependent duration of analgesia accompaniedby some sedation and systemic hypotension. Insheep the drug gave profound analgesia and somesedation with no hypotension (Eisenach et al.,1987).XylazineEpidural xylazine can provide profound analgesiain some animals without interfering with motoractivity (Caulkett et al., 1993). In cattle and llamasthe onset of analgesia occurs within 15 to 20 minutesand persists for 2 to 3 hours; in horses theonset is slower but the analgesia lasts longer. Bothhorses and cattle show signs of sedation anddecreased intestinal activity as well as slightataxia. In cattle the systemic signs can be antagonizedwithout loss of analgesia by systemic tolazoline(Skarda & Muir, 1990).ButorphanolA number of studies have failed to produce goodevidence that there is any advantage in administeringbutorphanol epidurally rather than i.v. butthe epidural route may have advantages in dogs(Troncy et al., 1996).BuprenorphineThe analgesia effects of epidural buprenorphineappear similar to those of epidural morphine. Theoccurrence of urinary retention is less likely withbuprenorphine since its intrathecal injection hasminimal effects on urodynamics in dogs (Drenger& Magora, 1989).α 2 adrenoceptor agonistsWhen epidural doses of α 2 adrenoceptor agonistsproduce analgesia it is usual to see signs of sedationas a result of systemic uptake. Of the availablecompounds clonidine, xylazine, detomidine andmedetomidine have been administered by theepidural route.DetomidineMainly used in horses, epidural detomidineproduces profound analgesia with ataxia andloss of proprioception. Skarda and Muir (1994)reported that 60 µg/kg administered at thefirst intercoccygeal space induced analgesia asfar cranially as the 4th thoracic segment. Onsetof analgesia was within 20 minutes and wasaccompanied by marked sedation, a reduction inheart and respiratory rates and an increase inPaCO 2 . Ko et al. (1992) failed to produce analgesiain pigs after epidural injection of massive doses ofdetomidine.MedetomidineEpidural medetomidine in cats produces sedationand, often, vomiting, which suggests that itseffects are mainly systemic following absorptionfrom the epidural space. Further evidence infavour of this is that it produces an initial increasein arterial blood pressure followed some 20 minuteslater by a decrease, while heart rate and respiratoryrates are both decreased.

LOCAL ANALGESIA 243NMDA antagonistsKetamine is known to have activity as a localanalgesic, an NMDA antagonist, an opioid agonist/antagonistand, possibly, as an antimuscarinic.These complex actions have made theevaluation of epidural ketamine difficult. In isofluraneanaesthetized dogs epidural ketamine(2mg/kg) is associated with minimal haemodynamiceffects (Martin et al., 1997). Further investigationis needed before epidural ketamine can berecommended.Miscellaneous drugsNSAIDs, corticosteroids anticholinesterases, inhibitorsof nitric oxide synthase, vasopressin andsomatostatin have all been shown to have somedegree of analgesic effect when administeredepidurally. Currently, none is used clinically byepidural injection.Continuous epidural blockContinuous spinal blocks can be used to providelong term analgesia and, with the correct choice ofdrugs and drug concentrations, animals can bekept both ambulatory and pain free after operationson the caudal limbs, perineum and tail. Thetechnique can also be used to prevent straining incases of rectal and vaginal prolapse. In mostinstances the catheter is introduced into theepidural rather than subarachnoid space and thedrugs are injected from a syringe in repeatedsmall, fractional doses, or by slow continuousinfusion using a syringe pump. The introductionof commercially available sterile packs of cathetersand suitable needles has made the use of continuousblocks attractive in many species of animal.The indications, advantages, contraindicationsand complications associated with continuousepidural block are similar to those of single injectiontechniques. The additional advantages of continuousblock are the ability to maintain analgesiafor long periods and to maintain a route for theinjection of opioids and other drugs during surgeryand postoperatively.To date, continuous epidural block has notbecome a routine technique in veterinary anaesthesiabecause of technical difficulties in catheterplacement, the potential for producing damage ofthe spinal cord, meninges and nerves, the risk ofintroducing infection and catheter related problems.However, practice should render the techniquesafer and its accomplishment lessformidable in all species of animal.Problems and hazards of epidural blockVery few drugs are specifically marketed forepidural or spinal use and those availablefor intramuscular or intravenous injectioncontain preservatives. Common preservatives aresodium bisulphite, benzethonium chloride,chlorbutanol and disodium EDTA. Their neurotoxicityis currently largely unknown. One preservative,methylparaben, does not appear to betoxic but has been associated with allergicresponses in man (Adams et al., 1977). Morphineis now marketed specifically for epidural use(‘Duramorph’) and this preparation is free frompreservatives.Testing for entry to the epidural space by loss ofresistance to injection of a small quantity of air as isoften used in children (Michel & Anaes, 1991) andsheep (Hall & Clarke, 1991) may be associatedwith incomplete or patchy absorption of epiduraldrugs, postoperative neurological deficits andeven air embolism. (Dalens et al., 1987; Stevens etal., 1989; Sethna & Berde, 1993).Arterial hypotension is more frequently theconsequence of toxic blood levels after absorptionor from undetected intravenous injection than theresult of sympathetic block. It seems probablefrom experience in a variety of animals that thesafety limits are to inject no more than 10 mg/kg oflignocaine and no more than 4 mg/kg of bupivacaine,but the maximal doses produced depend onthe speed of injection and the time to reach maximumplasma concentration.Catheters can be sheared off when pulled backwardthrough the insertion needle. Whenadvancement is impossible the needle and cathetershould be withdrawn together and the procedurerepeated. The management of cases where acatheter has sheared or broken is rather controversial,but a retained fragment is rarely a problem(Hurley & Lambert, 1990).

244 PRINCIPLES AND PROCEDURESPuncture of the dura is not dangerous if recognizedand does not contraindicate a secondattempt (preferably at another interspace) with aslow speed of injection. Total spinal block occurswhen dural puncture is not recognized and fulldoses intended for epidural injection are given.The first signs are changes in respiratory rate buthaemodynamic changes are minimal. The pupilsfirst become unequal, then dilated and apnoea follows.If the animal is intubated and ventilated withpure oxygen it is usually found that total spinalblock takes about one hour to wear off. If the situationis under control it is probably not necessary topostpone surgery.The major complication of a ‘bloody tap’, whenblood issues from the hub of a spinal needle, is thedanger of intravascular injection that can result incardiac toxicity.REFERENCESAdams, H., Mastri, A. and Charron, D. (1977)Morphological effects of subarachnoidmethylparaben on rabbit spinal cord. PharmacologicalResearch Communications 9: 547–551.Arndt, J.O. (1986) The low pressure system: theintegrated function of veins. European Journal ofAnaesthesiology 3: 343–370.Bernards, C.M., and Hill, H.F. (1990) Morphine andalfentanil permeability through the spinal dura,arachnoid and pia mater of dogs and monkeys.Anesthesiology 73: 1214–1219.Bouarth, K.H. and Saleh, A.S. (1985) Long-term paintreatment in the dog by peridural morphine.Proceedings of the 2nd International Congress ofAnesthesia, Sacramento, p. 161.Brook, G.B. (1930) Spinal (epidural) anaesthesiain cattle. Veterinary Record 10: 30–36.Brook, G.B. (1935) Spinal (epidural) anaesthesiain the domestic animal. A review of ourknowledge at the present time. VeterinaryRecord 15: 549–553; 576–581; 597–606; 631–635;659–667.Caulkett, N., Cribb, P.H., Duke, T. (1993) Xylazineepidural analgesia for cesarian section in cattle.Canadian Veterinary Journal 34: 674–676.Dalens, B., Bazin, J.E. and Haberer, J. P. (1987) Epiduralair bubbles a cause of incomplete analgesia duringepidural anesthesia. Anesthesia and Analgesia66: 697–683.Dickenson, A., Sullivan, A. and McQuay, H. (1990)Intrathecal etorphine, fentanyl and buprenorphine onspinal nociceptive neurones in the rat. Pain42: 227–234.Drenger, B., Magora, F., Evron, S. et al. (1986) The actionof intrathecal morphine and methadone on the lowerurinary tract of the dog. Journal of Urology135: 852–855.Drenger, B. and Magora, F. (1989) Urodynamic studiesafter intrathecal fentanyl and buprenorphine in thedog. Anesthesia and Analgesia 69: 348–353.Durant, P.A.C. and Yaksh, T.L. (1986) Distribution incerebrospinal fluid, blood and lymph of epidurallyinjected morphine and inulin in dogs. Anesthesia andAnalgesia 65: 583–592.Eisenach, J.C., Dewan, D.M., Rose, J.C. and Angelo, J.M.(1987) Epidural clonidine produces antinociception,but not hypotension in sheep. Anesthesiology66: 496–501.Emhke, H., Persson, P.B. and Kirchheim, H.R. (1987)A physiological role for pressure-dependent reninrelease in long term pressure control. PfluegersArchive European Journal of Physiology410: 450–456.Feldman, H. and Covino, B. (1988) Comparative motorblocking effects of bupivacaine and ropivacaine, anew amino amide local anesthetic in the rat and dog.Anesthesia and Analgesia 67: 1047–1052.Hall, L. W. and Clarke, K.W. (1991) VeterinaryAnaesthesia, 9th ed. London: Baillière Tindal, p. 263.Hurley, R.J. and Lambert, D.H. (1990) Continuous spinalanesthesia with a microcatheter technique;preliminary experience. Anesthesia and Analgesia70: 97–102.Jaffe, R.A. and Rowe, M.A. (1996) A comparison of thelocal anesthetic effects of meperidine, fentanyl andsufentanil on dorsal root axons. Anesthesia andAnalgesia 83: 776–781.Keates, A.S. (1988) Anesthesia mortality – a newmechanism. Anesthesiology 68: 2–4.Ko, J.C.H., Thurmon, J.C., Benson, J.G. et al. (1992)Comparison of epidural analgesia induced bydetomidine or xylazine in swine.Veterinary Surgery21: 82.Martin, D.D., Tranquilli, W.J., Olson, W.A., Thurmon,J.C. and Besson, G.J. (1997) Hemodynamic effects ofepidural ketamine in isoflurane anesthetized dogs.Veterinary Surgery 26: 505–509.Pablo, L.S. (1993) Epidural morphine in goats afterhindlimb orthopedic surgery. Veterinary Surgery22: 307–310.Peters, J., Kutkuhn, B., Medert, H.A., Schlaghecke, R.,Schuttler, J. and Arndt, J.O. (1990) Sympatheticblockade by epidural anesthesia attenuates thecardiovascular response to severe hypoxemia.Anesthesiology 72: 134–144.Peters, J., Schlaghecke, R., Thouet, H. and Arndt, J.O.(1990a) Endogenous vasopressin supports bloodpressure and prevents severe hypotension duringepidural anesthesia in conscious dogs. Anesthesiology73: 694–702.Popilskis S. Kohn, D., Sanchez J.A. and Gorman, P.(1991) Epidural vs. intramuscular oxymorphone

LOCAL ANALGESIA 245analgesia after thoracotomy in dogs. VeterinarySurgery 20: 462–467.Reiz, S., Häggmark, S. Johansson, G. and Nath, S. (1989)Cardiotoxicity of ropivacaine – a new amide localanaesthetic agent. Acta Anaesthesiologica Scandinavica33: 93–98.Sethna, N.F. and Berde, C.B. (1993) Venous airembolism during identification of the epiduralspace in children. Anesthesia and Analgesia76: 925–927.Share, L. (1988) Role of vasopressin in cardiovascularregulation. Physiological Reviews 68: 1248–1284.Skarda, R.T. and Muir, W.W. III (1990) Influence oftolazoline on caudal epidural administration ofxylazine in cattle. American Journal of VeterinaryResearch 51: 556–560.Stevens, R., Mikat-Stevens, M., Van Clief, M. et al. (1989)Deliberate epidural air injection in dogs: aradiographic study. Regional Anesthesia 14: 180–182.Troncy, E., Cuvelliez, S. and Blaise, D. (1996) Evaluationof analgesia and cardiorespiratory effects ofepidurally administered butorphanol in isofluraneanesthetizeddogs. American Journal of VeterinaryResearch 57: 1478–1482.Tung, A.S. and Yaksh, T.L. (1982) The antinociceptiveeffects of epidural opiates in the cat: Studies on thepharmacology and the effects of lipophilicity in spinalanalgesia. Pain 12: 343–356.Valverde, A., Little, C.B. Dyson, D.H. and Motter, C.H.(1990) Use of epidural morphine to relieve pain in ahorse. Canadian Veterinary Journal 31: 211–212.Vesal, N., Cribb, P. and Frketic, M. (1996) Postoperativeanalgesic and cardiopulmonary effects ofoxymorphone administered epidurally andintramuscularly, and medetomidine administeredepidurally: a comparative clinical study. VeterinarySurgery 25: 361–369.Wang, C., Chakrabarti, M.K. and Whitwam, J.G. (1993)Specific enhancement by fentanyl of the effects ofintrathecal bupivacaine on nociceptive afferent butnot sympathetic efferent pathways in dogs.Anesthesiology 79: 766–733.

Anaesthesia of the horse 11INTRODUCTIONProbably no other species of animal presents asmany special problems to the veterinary anaesthetistas the horse. Perioperative mortality rate inrelation to general anaesthesia in apparentlyhealthy horses is around 1% (Johnston et al., 1995)and has remained constant over at least 30 years(Hall, 1983; Tevik, 1983; Clarke & Gerring, 1990;Young & Taylor, 1993) despite increasing sophisticationof anaesthetic techniques and monitoring.However, lack of improvement in survival ratesresults mainly from the longer duration of manysurgical procedures which, without the advanceswhich have occurred, would have been impossibleto perform. Increased duration of anaesthesia significantlyincreases the risk (Johnston et al., 1995).The veterinary anaesthetist is faced with numerousdisturbances of cardiopulmonary and skeletalmuscle function associated with general anaesthesia,many of which are only very incompletelyunderstood. Their certain prevention is currentlyimpossible, and measures designed to overcomeone problem often only result in exacerbation ofanother. Developments in the provision of reliablesedation has enabled a wider range of proceduresto be carried out under local analgesia than wasonce considered practicable, but even this techniqueis not without risk (to horse and operator)and general anaesthesia still remains the onlyoption in many cases.SEDATION OF THE STANDING HORSEIt frequently is necessary to sedate horses to enableprocedures to be carried out easily and safely.Horses are not good subjects for sedation for if theyexperience a feeling of muscle weakness or ataxiathey may panic in a violent manner. Historically,the most effective sedative was, for many years,chloral hydrate, but its use required administrationof large volumes of solution and panicresponses to ataxia produced by it were occasionallyencountered. Other drugs used includedcannabis indica, bulbocapnine, bromides, and pentobarbitone(Amadon & Craige, 1936; Wright,1942). The introduction of the mood-altering ‘neuroleptic’agents, in particular the phenothiazines,followed in 1969 by xylazine (Clarke & Hall, 1969),and more recently other α 2 adrenoceptor agonists,has revolutionized equine sedation and, with theadditional use of local analgesic techniques, enablemany procedures to be performed in the standinganimal. However, even with modern agents, sedatedhorses must be handled with caution for theymay be aroused by stimulation and when disturbedcan respond with a very well aimed kick.PHENOTHIAZINESAcepromazineAcepromazine is the phenothiazine derivative mostwidely used in horses for both its mood-altering247

248 ANAESTHESIA OF THE SPECIESand sedative actions. Intravenous (i.v.) doses of0.03 mg/kg or intramuscular (i.m.) of 0.05 mg/kgexert a calming effect within 20–30 minutes ofinjection and, although at these dose rates obvioussedation may only be apparent in 60% of horses,they become much easier to handle. Doses may bedoubled, but the dose–response curve of acepromazineis such that the level of sedation does notalways increase, although the duration will.Acepromazine (in paste or tablet forms) also maybe given orally at maximally recommended dosesof 0.1 mg/kg. Oral availability in horses is highand can be equal to that of the i.m. route (Hashem& Keller, 1993). Acepromazine is very long acting,and elimination may be further delayed in old orsick animals, particularly in those with even mildliver disease.Acepromazine at the doses recommended haslittle effect on ventilation, but causes hypotensionthrough vasodilation, and hypovolaemic horsesmay faint. Tachycardia results from the fall in arterialblood pressure (ABP), but sometimes firstdegree atrioventicular block is seen. A very smallproportion of horses (the authors have seen twosuch cases) show aberrant reactions, and maybecome recumbent without there being any apparentcardiovascular cause; these reactions weremore common with other phenothiazine agents. Inmale animals effective sedation with phenothiazinederivatives is associated with protrusion ofthe flaccid penis or, on very rare occasions, priapism.In either case, physical damage to the penismust be avoided. In the vast majority of animalsthe penis retracts as sedation wears off; in a verysmall proportion prolonged prolapse occurs.Treatment of this complication is by manual massage,compression bandage and replacement in theprepuce followed by suture of the preputial orifice.It is the opinion of the authors that the low incidenceof this complication coupled with the possibilityof immediate treatment means that where aphenothiazine agent is the drug of choice its use isnot contraindicated in stallions or geldings.Acepromazine has proved a very safe agent inthe horse. The calming and low level sedativeeffects it produces make it the agent of choice forinterventions such as shoeing, and when used inyoung animals it appears to assist in training thehorse to tolerate many future procedures withoutsedation. When acepromazine is combined withopioid agents deep sedation is achieved, and suchcombinations may be used in cases where α 2adrenoceptor agonists alone would be inappropriate.Acepromazine is an excellent premedicantbefore general anaesthesia; it calms the horse priorto the insertion of catheters, lengthens the action ofthe anaesthetic agents, statistically reduces theanaesthetic risk in the horse (Johnston et al., 1995)and its prolonged duration of action means that itcontributes to a quiet recovery.α 2 ADRENOCEPTOR AGONISTSXylazineFollowing the introduction of xylazine for sedatinghorses, it rapidly gained in popularity becauseof the reliable sedation produced. Doses of0.5–1.1 mg/kg i.v. are followed within 2 minutesby obvious signs of effect. The horse’s head is loweredand the eyelids and lower lip droop (Clarke &Hall 1969; Kerr et al., 1972). Although the horsemay sway on its feet, cross its hindlegs or knuckleon a foreleg, it will remain on its feet and show nopanic. Sedation is maximal after about 5 minutesand lasts 30 to 60 minutes depending on the dose.Doses of 2 to 3 mg/kg i.m. give similar effects,maximal sedation being achieved 20 minutes afterinjection. Xylazine has analgesic properties, particularlyin colic (Pippi & Lumb, 1979; Lowe &Hilfiger, 1986; Jochle et al., 1989; England & Clarke,1996) and in colic cases analgesia is associated withthe marked reduction in gut movement caused bydrugs of this class. Horses sedated with xylazineremain very sensitive to touch and the apparentlywell sedated horse may, if disturbed, respond witha very sudden and accurate kick.The cardiopulmonary effects of xylazine inhorses have been well investigated (Muir et al.,1979a; Short, 1992; England & Clarke, 1996). Atransient rise in ABP peaks 1–2 minutes after i.v.injection; the pressure then slowly falls to belowresting values and remains depressed for at leastone hour. Concurrent with the hypertensive phasethere is profound bradycardia coupled with bothatrioventricular and sinoatrial heart block. Heartblock is at its most intense in the first few minutesand in many cases disappears as the heart rate

THE HORSE 249increases. Changes in ABP are dose dependent inintensity and duration, and following i.m. injectionchanges are similar but less marked. Cardiac output(CO) is significantly reduced, i.v. doses of1.1mg/kg causing falls of 20–40% of normal restingvalues. At doses of up to 1.1 mg/kg xylazinedoes not cause severe respiratory depressionalthough there may be a small rise in PaCO 2 and aslight decrease in PaO 2 . However, some upper airwayobstruction may occur. Heavy coated horsesmay sweat as sedation is waning – this is mostcommonly seen if atmospheric temperatures arehigh. Other side effects are those typical of α 2adrenoceptor agonists and include hyperglycaemia(Thurmon et al., 1982) and diuresis.Changes in insulin production and hyperglycaemiado not appear to be a feature of xylazineaction in neonatal foals (Robertson et al., 1990).When used as a premedicant, xylazine greatlyreduces the amount of both injectable and volatileanaesthetic agents subsequently required. In the 30years since its launch xylazine has become the‘gold standard’ for equine sedation and premedication,particularly in North America. In Europeuntil the advent of generic forms and alternativeagents forced prices to reduce to a realistic level, itsuse was limited by much higher pricing.DetomidineDetomidine, a very potent α 2 adrenoceptor agonistwas first used as a sedative and analgesicagent by Alitalo and Vainio in 1982, and since itsintroduction has gained great popularity for sedationand premedication of all types of horse(Vainio, 1985; Alitalo, 1986; Clarke & Taylor, 1986;Short, 1992). Initially very high doses (up to160 µg/kg) of detomidine were recommended butit soon became obvious that maximal sedativeeffects were obtained with i.v. doses of 20 µg/kgand that higher doses increased the durationrather than depth of sedation. Slightly higherdoses appear necessary to provide good analgesia(Hamm & Jochle, 1984). The concentrated but nonirritantform of 10 mg/ml in which detomidine (asDomosedan or Dormasedan) is provided makes itvery suitable for i.m. injection, doses approximatelytwice those given i.v. being required to producethe same effect.Detomidine has some effect when injected subcutaneously(SC) and is also absorbed throughmucous membranes. The latter property has beenutilized by administering the drug on sugarlumps, peppermint sweets or, more effectively,squirting it under the tongue (Malone & Clarke,1993). When given in food, the effect is less reliableas the drug is extensively metabolized by first passthrough the liver. The property of easy absorptionacross mucous membranes must, for reasons ofpersonal safety, be taken into account when handlingthe drug.The type of sedation produced by detomidine isidentical to that produced by xylazine; blind trialsfailed to identify which horses had been given1mg/kg xylazine i.v. and which 20 µg/kg detomidinei.v. (England et al., 1992), except by durationof action. As with xylazine, horses under detomidinesedation are sensitive to touch and may kick.Lower doses of detomidine do not always result inmaximal sedation, but may prove useful where ashort period of action is required. Detomidine premedicationreduces the dose of anaesthetic agentssubsequently required.The pharmacological properties of detomidineare typical of those of an α 2 adrenoceptor agonist.Following doses of 10–20 µg/kg i.v. cardiovascularchanges are very similar to those followingxylazine (Short, 1992), there being a markedbradycardia with heart block, coupled with arterialhypertension followed by hypotension. However,with higher doses the hypertensive phase isconsiderably more prolonged (Vainio, 1985; Shortet al., 1986). Whether this hypertension is then followedby prolonged hypotension has not beeninvestigated – most studies terminating whensedation ceases. At clinically used doses respirationis slowed and PaO 2 is slightly decreased.Some horses snore – presumably from congestionof the nasal mucous membranes. The authors havenoted occasional horses (usually those sufferingfrom toxaemic conditions) becoming tachypnoepicfor some 10–15 minutes after the administrationof detomidine. Similar reactions have beenobserved after other α 2 adrenoceptor agonistsxylazine, romifidine and medetomidine (Clarke &Gerring 1990; Bettschart et al., 1999a). Other effectsinclude reduction in gut motility, hyperglycaemia,sweating and an increase in urination. Doses

250 ANAESTHESIA OF THE SPECIESabove 60 µg/kg may cause swelling of the head;this problem appears to be associated with theprolonged head droop and can be prevented bypropping the head in a more normal position.Occasionally urticarial reactions have been noted;these are self-limiting and regress without treatment.Moderate doses of detomidine are claimedto be safe in pregnancy and many mares havereceived multiple doses throughout gestationwithout any maternal or foetal harm resulting.Abortion has been reported in a pony mare whichhad received detomidine (Katila & Oijala, 1988),but the authors considered the abortion was due toother causes.The actions of detomidine (and of other α 2adrenoceptor agonists) can be reversed by the specificantagonist, atipamezole. Dose rates from60–200 µg/kg have been used, that requireddepending on the degree of residual sedation(Nilsfors & Kvart 1986; Ramseyer et al., 1998;Bettschart et al., 1999a). At the doses of detomidinerecommended it is rare that antagonism isrequired, but the authors have been grateful of itsavailability in cases of overdosage of α 2 /opioidcombinations where a horse has become severelyataxic or even recumbent.reduces gut motility, the duration of this effectbeing dose dependant (Freeman, 1998). Self-limitingurticarial reactions may occur occasionally.The degree of analgesia produced by romifidinehas been questioned; Voegtli (1988) found thatanalgesia did occur but was not dose related orconsistent, whilst other work has suggested that itis devoid of analgesic activity (Hamm et al., 1995).Nevertheless, romifidine is widely used for premedicationand as part of anaesthetic combinationsit reduces the dose of anaesthetic agentssubsequently used.MedetomidineMedetomidine’s use has been investigated inhorses (Bryant et al., 1991; Bettschart et al., 1999).Doses of 5–7 µg/kg i.v. are sufficient to cause verydeep sedation with severe ataxia, and higher dosesmay result in recumbency. The marked hypnoticproperties make the agent unsuitable for routineuse as a sedative in horses. However, it appears tobe very short acting in the horse, and its excellentanalgesic and muscle relaxant properties meanthat it can be a useful agent as part of an anaestheticprocess.RomifidineRomifidine is a recent α 2 adrenoceptor agonistmarketed for use in horses. The type of sedationproduced by romifidine differs from that producedby the other α 2 adrenoceptor agonists;the horse’s head does not hang so low, andthere is considerably less ataxia (Voetgli, 1988;England et al., 1992). Nevertheless, doses of from40–120µg/kg i.v. result in sedation which enablesa range of clinical procedures to be performed. Inclinical practice romifidine has proved very popularwhere ataxia is particularly unwelcome, e.g. forshoeing. When used to sedate animals for surgicalprocedures, romifidine is generally combined withopioid agents as indeed are most α 2 adrenoceptoragonists. The pharmacological actions of romifidineother than sedation are similar to all α 2adrenoceptor agonists. Following i.v. administrationthere is bradycardia, a fall in CO, and hypertensionfollowed by lowered blood pressure(Clarke et al., 1991; Freeman, 1998). RomifidinePRACTICAL USE OF α 2 ADRENOCEPTORAGONISTS IN THE HORSE.The different manifestation of sedation and lack ofataxia with romifidine excepted, the remainingproperties, including all side effects, appear similarwith all three α 2 adrenoceptor agonists commonlyused in horses (Fig. 11.1). Thus choice willdepend on the duration of action required, theroute of administration, and on personal preferences.For example, all three agents provide excellentanalgesia in cases of colic, although thebradycardia and lack of gut motility induced mustbe considered in the subsequent assessment.Before a definitive diagnosis has been made in acolic case it is preferable to use xylazine or a lowdose (up to 20 µg/kg) of detomidine for sedationand analgesia, as high doses may mask signs indicatingthe requirement for surgery. Following adecision that surgery is required, the longer actingromifidine with its lack of ataxia, may be the mostsuitable analgesic for transportation. Although

THE HORSE 25150 Heart rate200 Mean arterial blood pressureHeart rate(beats/min)40302010Mean arterial blood pressure(mmHg)10000 2 5 10 15 30 45 60Time from injection (min)00 2 5 10 15 30 45 60Time from injection (min)120 Muzzle to floor distance20 Ataxia (sum of scores)Change in muzzleto floor distance %10080604020Ataxia score(sum from 5 ponies)1510500 5 10 15 30 45 6000 5 10 15 30 45 60Time from injection (min)Time from injection (min)Xylazine 1mg/kgDetomidine 0.02mg/kg (20 µg/kg)Romifidine 0.08mg/kg (80 µg/kg)FIG.11.1 Comparison of some of the sedative and cardiovascular effects of i.v.doses of xylazine (1mg/kg),detomidine(20µg/kg) and romifidine (80µg/kg).Data from 5 ponies.SE bars are omitted for the sake of clarity (from Clarke (1988),Clarke et al.,1991;England et al.,1992).there are no scientific studies of combining differentα 2 adrenoceptor agonists, in practical clinicaluse there are many reports of changing from one toanother at subsequent dosing; the effects appear tobe additive as expected.α 2 Adrenoceptor agonists have marked cardiopulmonaryside effects, and it is not surprisingthat occasional cases of collapse, or even of deathhave been reported following their use. Somereported cases may have resulted from intracarotidinjection, but where there is a delaybetween injection of the drug and the unexpectedevent, then such a reaction is probably druginduced. In dogs, xylazine sensitizes the heart toadrenaline induced arrhythmias but in horse suchsensitization has not been proved (W.W. Muir, personalcommunication). However, there are anecdotalreports of collapse in horses which are givenan α 2 adrenoceptor agonist when in a high state ofexcitement. Unfortunately immediate sedation isnecessary in many such situations, and in thesecases sufficient time must be left after drug administrationbefore further stimulation is applied. Insuch situations, the authors prefer combinations

252 ANAESTHESIA OF THE SPECIESwith acepromazine, which may reduce the risk.Clinical reports have suggested that combinationsof α 2 adrenoceptor agonists and potentiated sulfonamidesshould be avoided, although the scientificbasis of these observations is unproven.Some authorities premedicate horses with ananticholinergic agent (atropine or glycopyrrolate)prior to the administration of an α 2 adrenoceptoragonist, but use of such combinations is controversial.Anticholinergic drugs will prevent or reversethe bradycardia caused by α 2 adrenoceptor agonistsand will improve CO. However, the bradycardiaprotects against the hypertension caused byα 2 adrenoceptor agonist induced vasoconstrictionand once pulse rate rises, so does ABP (Alibhai &Clarke, 1996). Anticholinergic drugs, if used, mustbe given an adequate time prior to sedation; givingthe two drugs together is pointless.Infusions of α 2 adrenoceptor agonistsWhere α 2 adrenoceptor agonists are being used toprovide sedation for surgery, sometimes it is necessaryto increase their duration of action.Intermittent dosing, each increment being 25–50%of the original dose administered, is effective, butinfusion results in a more level and controllableplane of sedation. There are few scientific studiesas to the doses required; usually, the agent used isdiluted in a saline drip, then, following the initialloading dose, is infused to effect. The authorshave found that in conscious horses an infusionof 0.55 mg/kg/hour of xylazine provides goodsedation with minimal ataxia. Detomidine infusionsat 0.18 µg/kg/min have been demonstratedto provide steady sedation and to be appropriatefor intraoperative infusion (Wagner et al., 1992;Daunt et al., 1993). Infusions of 3.5 µg/kg/hour ofmedetomidine following a loading dose of 5 µg/kggive deep sedation and have also proved effectivein providing intraoperative analgesia withoutresulting in any delay of recovery (Bettschart et al.,1999).Administration of α 2 adrenoceptoragonists by other routesα 2 Adrenoceptor agonists are strong analgesicswhen administered by epidural or subarachnoidinjection. The caudal epidural administration of0.17 mg/kg of xylazine in 10 ml of normal salineproduces safe, effective perineal analgesia of 2.5hours duration in horses without apparent sideeffects (LeBlanc et al., 1988). More recently extensiveinvestigations have been carried out into theanalgesic and systemic effects of xylazine anddetomidine given by this route (Skarda & Muir1994; 1996a, b; 1998). To date there are no reports ofthe epidural adminstration of romifidine. Caudalepidural xylazine (0.25 mg/kg) gives perinealanalgesia and variable bilateral analgesia as farforward as S3 with minimal systemic effects. Inorder to obtain adequate perineal analgesia withepidural detomidine, doses of 60 µg/kg wererequired, which resulted in variable spread ofanalgesia sometimes extending to the thoracicregion. Systemic effects (e.g. bradycardia andsedation) suggested that a significant quantity ofdetomidine had been absorbed, and horses weresometimes very ataxic. However, when given bythe midsacral subarachnoid route, 30 µg/kg detomidinegave good analgesia from the coccyx to thelumbar region with minimal systemic effects.Systemic effects could be antagonized with agentssuch as atipamezole given systemically or by theepidural route. With either α 2 adrenoceptor agonist,onset of perineal analgesia occurred within15minutes. Skarda and Muir (1996a, b) suggestedthat xylazine was exerting a local anaestheticeffect, hence the low doses required in comparisonto those used when the drug is given systemically.α 2 Adrenoceptor agonists have also been givenby the epidural route in combination with opioidsand/or local anaesthetic agents.BENZODIAZEPINESDiazepam, midazolam, climazolam andzolazepamThe anxiolytic properties of diazepam are notobvious in horses and the drug should not be usedon its own as it gives rise to ataxia, sometimesassociated with panic, possibly through its musclerelaxing properties (Muir et al., 1982). Anotherbenzodiazepine, climazolam, has been found tohave similar properties and the antagonist sarmazenilhas been used to reverse its effects.

THE HORSE 253Although not useful as a sedatives in adult horsesthe benzodiazepine agents can be used in foalswhich will usually become recumbent followingi.v. 0.1–0.25 mg/kg of diazepam or midazolam (awater soluble benzodiazepine). The musclerelaxation induced by benzodiazepine agents isuseful during anaesthesia, and benzodiazepinessuch as diazepam, climazolam, midazolam andzolazepam have all been incorporated into anaestheticregimes used in adult horses.OTHER CATEGORIESChloral hydrateChloral hydrate was a popular sedative for horsesbut it has largely fallen into disuse because itsadministration poses problems and sedation isaccompanied by ataxia. Details of suitable dosescan be found in earlier editions of this book and itis still a useful component in some mixtures usedin equine anaesthesia.ReserpineReserpine has been employed for its prolongedcalming action, but has many side effects and doesnot give the type of sedation allowing veterinaryprocedures to be carried out easily (Tobin, 1978).DRUG COMBINATIONSIn the search for a completely reliable, safe methodof producing sedation in standing horses a numberof mixtures of drugs have been used.Appropriate doses of many of these have provedto have a more certain and profound effect thancan be regularly obtained from the use of any singledrug. However, the possibility of untowardreactions and appearance of as yet unrecognizeddrug interactions must always be consideredwhen these mixtures are employed.Acepromazine/α 2 adrenoceptor agonistcombinationsAcepromazine (0.02–0.05 mg/kg) and α 2 adrenoceptoragonists such as xylazine (0.5–1.0 mg/kg),detomidine (10–20 µg/kg) or romifidine (50–100 µg/kg) have often been used together forsedating horses. The prolonged calming action ofacepromazine is useful in a variety of circumstances,particularly if the horse was very excitedprior to sedation, both for premedication and incombination with opioids. Some North Americansources have considered that acepromazine andthe α 2 adrenoceptor agonists should not be usedtogether. The pharmacological reasoning behindthe suggestion that the two drugs should not begiven together rests on the fact that acepromazinecauses hypotension and the α 2 adrenoceptor agonistcauses bradycardia. However, the maximalbradycardia occurs within 1–2 minutes of injection,and at this time is accompanied by hypertension.If detomidine is given to horses alreadysedated with acepromazine, there is still a hypertensiveresponse, albeit starting from a lower base(Muir et al., 1979a). The authors have administeredxylazine, detomidine or romifidine to over 4000horses already sedated with acepromazine with noill effects (other than an increase in ataxia) and providingboth drugs are given at suitable doses thereis no reason why the combination cannot be used.Sedative/opioid combinationsThe pharmacological basis for combination ofsedatives with opioids has already been discussed(Chapter 4). Their use in the horse is not new(Martin & Beck, 1956; Klein, 1975) and a very largenumber of such combinations have been investigatedand advocated for use in this species of animal(Martin & Beck, 1956; Muir et al., 1979b;Robertson & Muir 1983; Nolan & Hall, 1984;Clarke & Paton, 1988). The addition of opioids,even at subanalgesic doses, appears to enhancesedation dramatically and, in particular, diminishesthe response to touch, thus reducing the likelihoodof provoking well directed kicks from thesedated horse. The disadvantage is that ataxia isalso increased (particularly with combinationsinvolving methadone or butorphanol), and occasionallya horse may become recumbent. Opioidexcitement reactions such as aimless walking mayoccur when sedation becomes inadequate and it isirrational to combine a short acting sedative suchas xylazine with opioids with long actions suchas buprenorphine or high doses of morphine.

254 ANAESTHESIA OF THE SPECIESTABLE 11.1 Some of the sedative/opioidcombinations that have been satisfactorilyused;there are many other combinationswhich are likely to be as satisfactorySedative 1 Sedative 2 OpioidAcepromazine,Methadone,0.05–0.10 mg/kg 0.05–0.10 mg/kgorButorphanol,0.02–0.04 mg/kgAcepromazine, Xylazine,0.5 mg/kg0.02–0.05 mg/kg orDetomidine,0.01 mg/kgorRomifidine,0.04–0.08 mg/kgAcepromazine, Detomidine, Butorphanol,0.04–0.06 mg/kg 0.01 mg/kg 0.01–0.02 mg/kgorMethadone,0.05 mg/kgXylazine,Butorphanol,0.5–0.6 mg/kg or 0.02–0.05 mg/kgDetomidine,or Methadone,0.010–0.015 mg/kg 0.05–0.10 mg/kg.or Romifidine,0.04–0.08 mg/kgAcepromazine has a very long action so problemsare less when this is part of the combination. Theincidence of opioid-induced excitement occurringcan be reduced by administering sedatives firstfollowed by opioids once sedation is apparent,although if the opioid concerned is one which hasa delayed onset of action (e.g. buprenorphine), thisis neither necessary nor desirable.Table 11.1 lists some of the sedative/opioidcombinations that have been satisfactorily used,but there are many other potential combinationswhich are likely to be as satisfactory. The dose ofopioid required is considerably less than that producinganalgesia (and with these combinations,local analgesia should still be employed for surgery).In recent years the most popular opioid foruse in such combinations has been butorphanol,which has the advantage of not being subject tosuch strict control regulations as the pure agonists.In the UK the combination of i.v. detomidine(10–15 µg/kg) or romifidine (40–120 µg/kg) andbutorphanol (0.02 mg/kg) has proved very successful,particularly for clipping fractious horses.Prolonged sedation can be achieved by initialdosage of both agents followed by an infusion ofthe α 2 adrenoceptor; often further dosing of theopioid is not needed, although this depends on theduration of action of the agent chosen. Caution isneeded to prevent cross contamination of thedrugs in their multi-dose bottles; the authors haveseen several cases of gross overdosage (the horsebecoming very ataxic, or recumbent) where thishas occurred.ANALGESIAAs with all species, the perioperative analgesicrequirements in the horse are generally met bynon-steroidal analgesics, opioid analgesics andlocal analgesics. In certain circumstances α 2adrenoceptor agonists and agents used as anaestheticagents, such as ketamine, also play a part inthe provision of analgesia.NON-STEROIDAL ANTI-INFLAMMATORYANALGESICS (NSAIDs)Non-steroidal anti-inflammatory agents arewidely used in horses for the provision of analgesiafor acute pain, for their anti-inflammatoryaction in injury and disease, for anti-endotoxaemicactions and for the provision of analgesia in chronicpain. Although they have not been shown to provideany intraoperative analgesia (Alibhai &Clarke, 1996), they are often administered atpremedication or intraoperatively so that theiranalgesic and anti-inflammatory actions will beeffective at the time of recovery.For many years, phenylbutazone was the NSAIDof choice for equine use, and it still remains aninexpensive and very effective agent that may begiven by injection in the immediate perioperativeperiod, then orally for continuing postoperativecare. Although it can cause toxic reactions, theseare well known, and can be avoided with correctdosing schedules. However, currently in Europe itmay not be used in food animals, and in manycountries this includes horses. Other older agentsused in the horse include dipyrone and meclofenicacid. In the last 10 years the most popular NSAID

THE HORSE 255for use in the horse has been flunixin meglumate,which gives excellent analgesia in a wide varietyof circumstances. Several of the new, very effectiveand potentially less toxic NSAIDs including carprofen,cedaprofen and ketoprofen are marketedin oral and/or injectable formulations for horses,and others may soon become available.The major problem with NSAIDs is their hightoxicity and fairly low therapeutic index and,although in theory the newer COX 2 sparingagents such as carprofen and vedaprofen shouldcause fewer problems, it will be only after someyears of use that lack of toxic effects will be confirmed.The major sites of toxicity of the NSAIDsare the gastrointestinal tract, kidneys, liver and theblood cells. In horses, the gastrointestinal tractappears the organ most affected, overdose of theagent causing stomach ulceration, and also damageto other areas, including the large bowel, leadingto diarrhoea. In the horse renal damage, evenin the presence of hypotension, is not common,and NSAIDs are administered before or duringanaesthesia without apparent problems. Liverdamage due to NSAIDs has been reported in oldhorses maintained on NSAIDs, and blooddyscrasias have occurred in horses given highdoses of phenylbutazone. Many of the injectablepreparations are contraindicated for i.m. use in thehorse as they cause local irritation. At least one i.v.preparation of phenylbutazone can cause severecardiac arrhythmias if injected too fast (probablybecause of the solvent, rather than the drug), so inthe absence of evidence to the contrary, it is best toadminister all i.v. NSAIDs slowly, especially inanaesthetized horses.The pharmacokinetics of NSAIDs vary greatlybetween species. In normal horses, the half-lives ofsome of the commonly used agents are as follows:●●●●●●Phenylbutazone: 4.5–9.0 hoursFlunixin: 1.6–2.1 hoursMeloxycam: 3 hoursCarprofen: 18 hoursVedaprofen: 6–8 hoursKetoprofen: 0.7–1.0 hour.(Cunningham & Lees 1995; product informationsheets).Breakdown products of some agents are themselvesactive. Knowledge of the half-life is necessaryto assess dosing schedules but efficacy mayoutlast effective blood levels as in some cases theNSAID is concentrated in the inflammatory fluidat the site of injury. Toxic effects, most commonlymanifest by diarrhoea, are usually due to cumulation,and are most likely to occur some days intothe postoperative period. It is therefore veryimportant not to exceed the data sheet recommendationsfor doses and frequency of dosing, and torealise that if more than one NSAID is employed,their toxic effects will be cumulative. Even if themanufacturers guidelines are kept, toxicity may begreater than expected in a sick horse, for examplein shocked animals, or in hypoproteinaemia(NSAIDs are highly protein bound).NSAIDs are widely used as analgesics for colicbut the response may be variable – sometimesthere is complete relief from pain, even in caseswhere there is non-viable intestine, whilst anothercase with an identical lesion may show no remissionof symptoms. NSAIDs prevent the onset ofsymptoms of endotoxaemia, such as the increasein pulse rate and in PCV. Prevention of thesechanges coupled with analgesia may preventrecognition of the onset of ‘shock’ and diagnosis ofsurgical conditions. Thus, it is better if NSAIDs arenot given to horses with colic until there is a definitivediagnosis, and a decision for surgery (or not) ismade. When using NSAIDs in the postoperativeperiod in colic cases consideration must be givento the effect of altered blood protein levels, and ofcirculation (which may increase half-life) on theirpharmacokinetics. It is difficult to distinguishwhether diarrhoea following surgery for colic isdue to endotoxaemia or is, itself, due to the toxicityof the NSAIDs used.OPIOID ANALGESICSOpioid analgesics are now widely used in thehorse to provide analgesia during and after surgery,as well as in combination with sedativeagents for restraint. As in all other species of animal,they cause a dose-related respiratory depression.The cardiovascular effects of high dosesinclude tachycardia and arterial hypertension,although at clinical dose rates such responses areminimal (Muir et al., 1978a). Excitement can occurfollowing their use, depending on dosage and

256 ANAESTHESIA OF THE SPECIESTABLE 11.2 Doses of opioids for producinganalgesi;i.m.injection minimizes the risk ofexcitement reactionsOpioidMorphineMethadoneOxymorphonePethidineBuprenorphineButorphanolwhether or not the horse is in pain at the time oftheir administration. Excitement is manifest in variousways from muzzle twitching, muscularspasms, ataxia, snatching at food, uncontrollablewalking through to violent excitement. Tobinand co-workers (Tobin & Combie, 1982) developeda ‘step-counting’ method of measuring the -walking or locomotor response and obtaineddose–response curves very similar to thoseobtained for analgesia. It is probable that many ofthese responses are due to stimulation of µ(OP3)receptors.The assessment of analgesic activity is very difficult.Drugs may affect different types of pain indifferent ways and despite a variety of experimentalmethods of assessment it is not easy to be certainof the most effective dose in any clinical circumstance.Table 11.2 lists suggested doses for someopioids but it must be remembered that theresponse obtained (both of analgesia and sideeffects) will depend on many factors such as thepresence or absence of pre-existing pain and thepresence of sedative or anaesthetic drugs.Pure agonistsDose and route0.05–0.1 mg/kg i.v.or i.m.Up to0.25 mg/kg i.m.0.1 mg/kg i.v.or i.m.0.05–0.3 mg/kg i.v.or i.m.1–2 mg/kg i.m.only0.006 mg/kg i.v.or i.m.0.05–0.10 mg/kg i.v.MorphineOf the agonist drugs, morphine is still to be regardedas an excellent postoperative analgesic, butthere is controversy as to the most effective dose.Classically, a suitable dose is said to be 0.1 mg/kg,but even this dose may cause dysphoria (Muir et al.,1978a). However, Combie et al., (1979; 1981) foundthat doses of up to 0.3 mg/kg produced minimalbehavioural effects, although they did commentthat any locomotor response was delayed.MethadoneMethadone (0.1 mg/kg i.v. or i.m.) is popular foruse in the horse, both as an analgesic and in sedative/opioidcombinations.Pethidine (meperidine)Pethidine (meperidine) has been one of the mostwidely used opioids in horses (Archer, 1947;Combie et al., 1979) especially for spasmodic colicas it has an antispasmodic action. Doses of up to2 mg/kg have been recommended and theseappear to produce good analgesia with moderatesedation. Pethidine does have several drawbacks.It is comparatively short acting (Alexander &Collett, 1974) and analgesia rarely lasts more thantwo hours. Following i.v. use excitement reactionsare common. A small but significant number ofhorses suffer anaphylactoid reactions (Clutton,1987) manifest by severe sweating, shaking andeven collapse. Anaphylactoid reactions are lesscommon and less severe when pethidine is given byi.m. injection; excitement is also less common andso this route should be considered the one of choice.Partial agonistsThe advantage of the partial agonist opioid drugsis that they are often less addictive in man andtherefore subject to less control regulations thanare pure agonist agents. Controversy concerningtheir most suitable doses for horses may bebecause dose–response effects occur in whichhigher doses antagonize analgesia already produced,so if, in clinical use, analgesia is notobtained it is inadvisable to increase the dose, andanother analgesic should be used.PentazocinePentazocine has been used in horses in NorthAmerica. Dose recommendations are very variable,ranging from 0.9 to 2.2 mg/kg.ButorphanolButorphanol is used to provide analgesia in premedication,during surgery, for postoperativeanalgesia and in sedative/opioid combinations.

THE HORSE 257Again, dose recommendations vary widely. Theminimal analgesic dose is 0.1 mg/kg i.v. but analgesiais transient, higher doses being required forlonger effective pain relief (Robertson et al., 1981;Kalpravidh et al., 1984). Doses of 0.2 mg/kg i.v.have been claimed to produce effective analgesiain equine colic for up to two hours. Cardiovasculareffects appear to be minimal but all studies of itsuse in pain-free animals found it to producebehavioural effects – nose-twitches, ataxia, shiveringbox walking and restlessness at doses as low as0.1 mg/kg i.v. Differences may be due to whetheror not the horse is in pain but, in the authors’experience of the use of this drug alone as an analgesic,doses of 0.1 mg/kg i.v. given to horses withmild colic pain cause the horse to walk constantlyaround the box for one hour (a locomotorresponse), and such a response could be disastrousin postoperative orthopaedic cases.BuprenorphineBuprenorphine, another partial agonist, givesanalgesia for about eight hours although it must beremembered that even after i.v. injection onset ofanalgesia requires at least 15 minutes. The authorshave found in clinical practice that doses of0.006mg/kg i.m. or i.v. to the horse in pain apparentlygive good analgesia for several hours.Additional routes of administration ofopioid agentsMorphine has been administered into joints followingarthroscopy. This is effective in man presumablythrough its action on specific opioidreceptors in the synovium (Lawrence et al., 1992)but claims of its efficacy in the horse have yet to besubstantiated. When morphine (15 mg in 5 ml ofsaline) is injected into the joints of ponies, the morphineplasma levels do not reach those likely toresult in systemic effects, whilst morphine is stilldetectable in joint fluid for at least 24 hours(Raekallio et al., 1997). Morphine (in a preparationwhich does not contain preservatives) may begiven by caudal epidural injection at doses of0.1mg/kg. Robinson et al., (1994) found that caudalepidural injection of 50 mg of morphine in10mls of saline resulted in analgesia of at least fivedermatomes and in some animals analgesiaspread considerably further cranially. Analgesialasted for 17 hours, but onset of analgesia wasdelayed for up to eight hours. When a higher doseof morphine (100 mg) was used, onset of analgesiawas faster (six hours), lasted longer (19 hours) andspread further (sometimes as far as T9) but thesigns of sedation, presumably through systemicabsorption of the drug, were greater. There aremany anecdotal reports from clinical practice as tothe efficacy of epidural morphine in providingpostoperative analgesia of the hind limbs and evenof the abdomen of individual animals, but fewmention the very prolonged onset of analgesiceffects. In practice, frequently morphine is used incombination with other agents. Sysel et al., (1996;1997) demonstrated that morphine (0.2 mg/kg)and detomidine (30 µg/kg) given through anepidural catheter situated at approximately thelumbosacral junction reduced experimentally inducedlameness within an a hour; that there wasminimal ataxia (the horses could trot); that thisanalgesia lasted for at least six hours after drugadministration and that incremental dosing couldbe used to maintain analgesia for up to 14 days.LOCAL ANALGESIAThe many techniques of nerve block used in horsesfor purely diagnostic purposes and the methodsfor producing intrasynovial desensitization willnot be considered here. Details of these techniquescan be obtained from surgical textbooks or fromDie Narkose der Tiere, volume 1, Lokalanasthesie, byWesthues and Fritsch (Westhues and Fristch,1960). Those to be described here are only the oneswhich the authors have found useful in operativesurgery or for giving pain relief (Fig. 11.2).SPECIFIC NERVE BLOCKSInfraorbital nerve blockThe infraorbital nerve is the continuation of themaxillary division of the Vth cranial nerve and isentirely sensory. During its course along the infraorbitalcanal it supplies branches to the uppermolar, canine and incisor teeth on that side, and

258 ANAESTHESIA OF THE SPECIEStheir alveoli and contiguous gum. The nerves supplyingthe first and second molars (PM1 and 2), thecanine and incisors, arise within the canal about2.5 cm from the infraorbital foramen and pass forwardsin the maxilla and premaxilla to the teeth.The nerves to cheek teeth three to six (PM3, Ml,2 and 3) pass directly from the parent nerve trunkin the upper parts of the canal. After emergingfrom the foramen the nerve supplies sensory fibresto the upper lip and cheek, the nostrils and lowerparts of the face.The infraorbital nerve may be approached attwo sites:1. At its point of emergence from theinfraorbital foramen: the area desensitized willcomprise the skin of the lip, nostril and face on thatside up to the level of the foramen2. Within the canal, via the infraorbital foramen,when in addition the first and second premolars,the canine and incisor teeth with their alveoli andgum, and the skin as high as the level of the innercanthus of the eye, will be influenced (Fig. 11.3).The lip of the infraorbital foramen can be detectedreadily as a bony ridge lying beneath the edge ofthe flat levator nasolabialis muscle. When it isdesired to block the nerve within the canal it is necessaryto pass the needle up the canal about 2.5 cm.To do this the needle must be inserted through theskin about 2 cm in front of the foramen afterreflecting the edge of the levator muscle upwards.An insensitive skin weal is an advantage. For theperineural injection a needle 19 gauge (1.1 mm),5 cm long, is suitable. The quantity of local analgesicsolution required will vary from 4 to 5 ml. Forblocking the nerve at its point of emergence fromthe canal, the needle is introduced until its pointcan be felt beneath the bony lip of the foramen.From 4 to 5 ml of 1% mepivacaine is injected, withdrawingthe needle slightly as injection proceeds.Loss of sensation should follow in 15–20 minutesand last a further 30–40 minutes if the solutioninjected contains a vasoconstrictor.Injections at site 1 may be employed for interferencesabout the lips and nostrils, such as suturingof wounds, removal of polypi, etc. Extractionof canine or incisor teeth is seldom required inhorses, and for extraction of molar teeth generalanaesthesia is usually preferred. For trephiningFIG.11.2 Sites for insertion of the needle to block thesupraorbital,infraorbital,mental and mandibular nerves.the facial sinuses, local infiltration analgesia offersa good alternative.Mandibular nerve blockThe alveolar branch of the mandibular division ofthe Vth cranial nerve enters the mandibular foramenon the medial aspect of the vertical ramus ofthe mandible under cover of the medial pterygoidmuscle. It traverses the mandibular canal, givingoff dental and alveolar branches on that side, andemerges through the mental foramen. From thispoint it is styled the mental nerve. The nerves supplyingthe canine and incisor teeth arise from theparent trunk within the canal 3–5 cm behind themental foramen, and pass to the teeth within thebone.If the mandibular alveolar nerve is injected atits point of entry into the mandibular canal at themandibular foramen, practically the whole of thelower jaw and all the teeth and alveoli on that sidewill become desensitized. The technique is difficultand uncertain, for the nerve enters the canalhigh up on the medial aspect of the vertical ramus.The foramen lies practically opposite the point ofintersection of a line passing vertically downwardsfrom the lateral canthus of the eye, and oneextending backwards from the tables of themandibular molar teeth.A point is selected on the caudal border of themandible about 3 cm below the temporomandibulararticulation. After penetrating the skin the needleis allowed to lie in the depression between the

THE HORSE 259incisor teeth will also be desensitized) but this isnot easily performed.The mental foramen is situated on the lateralaspect of the ramus in the middle of the interdentalspace. It can be palpated after deflecting thepencil-like tendon of the depressor labii inferiorismuscle upwards. The nerve may be detected as anemerging thick straw-like structure. From thispoint the technique is the same as that outlined forthe infraorbital nerve.FIG.11.3 Area of skin desensitized after blocking:theinfraorbital nerve within the canal (transverse lines),thesupaorbital nerve (vertical lines) and the mental nerve(spotted).wing of the atlas and the base of the ear. The needleis advanced as its point is depressed until it passesdeep to the medial border of the ramus. It is thenadvanced further in the direction of the point ofintersection of the previously mentioned lines,keeping as close as possible to the medial surface ofthe mandible but, as the nerve lies medial to theaccompanying artery and vein, the needle does notneed to follow the bone closely. Following thismethod the needle should lie parallel with the nervefor a distance of 3–4 cm. About 5 ml of analgesicsolution is injected along this length. Germanwriters describe a modification: the foramen isapproached from the ventral border of the ramus,just in front of the angle. The point of the needlemust penetrate a distance of 1.0–1.5 cm to reach theforamen.The chief indications are molar dental interferencesin the lower jaw, but most surgeons todayprefer to carry out all dental surgery under generalanaesthesia and this nerve block will only be usedwhen, for some reason, general anaesthesia isimpracticable.Mental nerve blockSuturing of wounds of the lower lip may be conveientlycarried out under mental nerve block.The nerve can be injected as it emerges fromthe mental foramen and analgesia of the lowerlip on that side will ensue (Fig. 11.3). Attemptsmay be made to pass the needle along a canal adistance of 3–5 cm (in which case the canine andSupraorbital nerve blockSuturing of wounds involving only the uppereyelid is easily possible after block of the supraorbitalnerve (Fig. 11.3). The supraorbital (orfrontal) nerve is one of the terminal branches of theophthalmic division of the Vth cranial nerve. Itemerges from the orbit accompanied by the arterythrough the supraorbital foramen in the supraorbitalprocess. It supplies sensory fibres to the uppereyelid and, in part, to the skin of the forehead. Thenerve is injected within the supraorbital foramen.The upper and lower borders of the supraorbitalprocess, close to its junction with the mainmass of the frontal bone, is palpable. The foramenis recognized as a pit-like depression midwaybetween the two borders. The skin is prepared andan insensitive weal produced. A needle, 19 gauge(1.1 mm), 2.2 cm long, is passed into the foramen toa depth of 0.5–1.0 cm and 5 ml of analgesic solutioninjected.Auriculopalpebral nerve blockThe auriculopalpebral nerve is a terminal branchof the facial division of the trigeminal (Vth) cranialnerve innervating the orbicularis oculi muscles.Blocking it prevents voluntary closure of theeyelids but does not in any way desensitize them.In conjunction with topical analgesia of theconjunctiva it is most useful for examination ofthe eye, as well as for the removal of foreignbodies from the cornea and other minor eye surgery.It may be blocked by placing 5 ml of 2%mepivacaine solution subfascially at the mostdorsal point of the zygomatic arch. A 2.5 cm,22 gauge (0.7 mm) needle is a convenient size forthis injection.

260 ANAESTHESIA OF THE SPECIESPalmar/plantar nerve blockThe nerves confer sensibility to the digit. Themedial palmar nerve of the forelimb is one of theterminal branches of the median nerve. At thelevel of the proximal sesamoid bones the trunk ofthe nerve divides into three digital branches, andall three branches are in close relationship with thedigital vessels. The dorsal branch in front of thevein distributes cutaneous branches to the front ofthe digit, and terminates in the coronary cushion.The middle branch, which is small and irregular,descends between the artery and vein. It is generallyformed by the union of several smallerbranches which cross forwards over the arterybefore uniting, and it terminates in the sensitivelaminae and the coronary cushion. The palmarbranch lies close behind the artery, except at themetacarpophalangeal joint, where the nerve isalmost superposed to the artery. It accompaniesthe digital artery in the hoof, and passes with thepalmar branch of that vessel to be distributed tothe distal phalanx and sensitive laminae.The lateral palmar nerve is formed by fusion ofthe termination of the ulnar nerve with one of theterminal branches of the median. In the metacarpalregion it occupies, on the outside of the limb, aposition on the flexor tendons analogous to that ofthe medial palmar nerve on the inside. Unlike thelatter nerve, however, it is accompanied by only asingle vessel – the lateral palmar vein – which liesin front of it. (A small artery – the lateral palmarmetacarpal artery – accompanies the nerve andvein from the carpus to the metacarpophalangealjoint on the lateral aspect of the limb). At the levelof the sesamoid bones it divides into three digitalbranches exactly as does the medial palmar nervealready described.In the hindlimb, plantar nerves result frombifurcation of the tibial nerve when it gains theback of the tarsus. They accompany the deep digitalflexor tendon in the tarsal sheath and, divergingfrom one another, they descend in the metatarsalregion, one at each side of the deep digital flexortendon. Each is accompanied in the metatarsus bythe metatarsal vein of that side, and by a slenderartery from the vascular arch at the back of the tarsus.A little below the middle of the metatarsus themedial nerve detaches a considerable branch thatwinds obliquely downwards and outwardsbehind the flexor tendons to join the lateral plantarnerve about the level of the button of the fourthmetatarsal bone. At the metatarsophalangeal joint,each nerve, coming into relation with the digitalvessels, resolves itself into three branches for thesupply of the digit.In the hindlimb the main artery – the dorsalmetatarsal artery – passes to the back of themetatarsus by dipping under the free end of the4th metatarsal bone, and finally bifurcates abovethe fetlock, between the two divisions of the suspensoryligament, to form the digital arteries. Inthe pastern region the disposition of the nervesand vessels is the same as in the forelimb. Plantarnerve block does not give the same results as palmarblock in the forelimb. The skin and deeper tissueson the dorsal aspect of the hind fetlock andpastern are innervated by terminal branches of thefibular nerve. This may be important from a surgicalstandpoint although less important from adiagnostic point of view (S. Dyson, personal communication,1991).Technique for palmar/plantar (abaxial sesamoid)injectionInjection in both fore- and hindlimbs is where thenerves course just proximal to the metacarpophalangeal/metatarsophalangealjoint. Although thenerves divide up into three branches at about thispoint the injection of 2–3 ml of local analgesic solutionmedially and laterally still produces completedesensitization of the entire foot (Fig. 11.4) Anadvantage of this site is that when the limb is heldup and the joint flexed, the nerves and their associatedvessels can be palpated so their accurate locationis easy.A strict aseptic technique must be practised andthe lateral and medial sites should be clipped andprepared as for an operation. In thin-skinnedhorses a 25 gauge (0.5 mm), 2.5 cm long needle isused; disposable needles can usually be introducedthrough the skin without the horse showingresentment.After the injections have been completed theanimal is allowed to stand quietly for 10–15 minutes.At the end of this time the limb is tested forsensation by tapping on the skin with a blunt-

THE HORSE 261FIG.11.4 Area of skin desensitized after bilateral plantaror palmar nerve block.ended spike on the end of a short pole. This is abetter way of detecting loss of deep sensation thanpricking with a needle. Any response to tappingaround the coronet and heel indicates failure toblock the nerve on that side. One indication of sensationis sufficient to prove this, and successive trialsonly serve to agitate the animal. It may benecessary to cover the animal’s eye to prevent itseeing the approach of the test instrument.Technique of palmar/plantar metacarpal/metatarsalinjectionAn alternative site for blocking the palmar/plantardigital nerves is from 5 to 7 cm proximal to themetacarpophalangeal/metatarsophalangeal jointat the level of the distal enlargements of the 2ndand 4th metacarpal or metatarsal bones. Thisensures that the analgesic solution is in contactwith the nerve proximal to its point of division.The local analgesic is injected into the groovebetween the deep digital flexor tendon and thesuspensory ligament. The nerve lies deep tothe subcutaneous fascia immediately in front ofthe deep flexor tendon. A 25 gauge (0.5 mm) needle1.2 cm long is used. The skin over the site is clippedand cleansed. In the great majority of cases theneedle can be inserted without movement on thepart of the animal. With the animal standing on thelimb, the skin and subcutaneous fascia are tense,and it is easy to penetrate the latter and thusensure that the subsequent injection is in directcontact with the nerve. If the limb is held raisedduring insertion of the needle, the flaccidity of theskin may cause the point to enter the subcutaneousconnective tissue and the method will fail. If bloodescapes from the needle, it should be partiallywithdrawn, redirected and reinserted. It may bedecided, first, to provoke an insensitive skin weal,and then pass the needle through this at the appropriateangle until its point lies beneath the fascia.When it is intended to block both sides of thelimb supplied by these nerves, the opposite side ofthe leg is similarly dealt with. When dealing withthe medial nerve it is necessary to work around theopposite leg. With the horse standing squarely,the operator passes one hand around the front ofthe adjacent leg for inserting the needle, while theother is passed behind the limb for holding thesyringe to the needle.The most likely cause of failure is that the solutionwas injected into the subcutaneous connectivetissue, and not beneath the fascia. Fortunately theskin at the site is now desensitized and a secondand deeper injection can be made withoutrestraint.About 2.5–5.0 ml of 1% mepivacaine or 0.5%bupivacaine solution is commonly injected aroundeach nerve. The average hunter is given 3 ml overeach nerve. In the hindlimb the technique is similar,except that the procedure exposes the operatorto a greater risk of injury, especially when dealingwith a nervous animal. Thus, not only must theanimal be twitched, but the forelimb raised inaddition if the operation is to be carried out withthe animal standing on the affected limb. Shouldthe operator feel indisposed to make the injectionwith the hindleg free, it may be raised by an assistant,but the needle must be inserted sufficientlydeeply to penetrate the fascia.Technique of blocking palmar terminal digital nervesThe terminal divisions of the palmar and plantarnerves may be subjected to medial and lateral perineuralinjection in the pastern region. The site forinjection is midway between the fetlock joint andcoronet. The palmar or volar border of the firstphalanx is located, and the dorsal edge of the (atthis point flattened) deep digital flexor tendon ispalpated. The nerve lies immediately dorsal to thetendon. About 2 ml of 1% mepivacaine or 0.5%

262 ANAESTHESIA OF THE SPECIESbupivacaine solution is injected SC just proximalto the collateral cartilages. The area desensitized islimited to the palmar or volar part of the foot andheel on that side.Indications for palmar/plantar blockPalmar/plantar block is commonly used to aiddiagnosis of the site of lameness, but it is also veryuseful to relieve the pain of acutely painful lesionsabout the foot, and to allow the animal to rest. Thepractice may be repeated daily for a few days insevere cases. Longest pain relief is obtained byusing bupivacaine with a vasoconstrictor such asadrenaline at a concentration of 1:200 000.The nerve blocks allow the painless performanceof palmar and plantar neurectomy and ofoperations about the foot, coronet and heel, suchas exposure of a corn or gathered nail track, partialoperations for quittor and sandcrack. Even whenoperations about the foot are performed undergeneral anaesthesia, palmar and plantar blockscan provide analgesia intraoperatively and in therecovery period. The desensitization of the footwhich they produce does not seem to be an obstacleto the animal regaining its feet after generalanaesthesia or to contribute to ataxia immediatelyafterwards.The complete desensitization of theforelimb below the carpusSimultaneous block of the median, ulnar and musculocutaneous(cutaneous branch) nerves desensitizethe entire manus.Median nerveThe best site at which to inject the median nerve isthe one used for the operation of median neurectomy,i.e. the point on the medial aspect of thelimb about 5 cm distal to the elbow joint, where thenerve lies immediately caudal to the radius andcranial to the muscular belly of the internal flexorof the metacarpus, deep to the caudal superficialpectoral muscle and the deep fascia.With the animal standing squarely, the administratorstoops adjacent to and slightly behind theopposite forelimb. The caudal border of the radiusFIG.11.5 Areas of skin desensitization after block of theulnar (shaded) and median nerves (spotted) (S.Dyson,personal communication,1991).where it meets the distal edge of the caudal superficialpectoral muscle is located with a finger. Thepoint of insertion of the needle is immediatelyproximal to the finger. A needle, 19 gauge(1.1mm), 2.5–3.0 cm long, is suitable. It is directedproximally and axially at an angle of 20 ° to the vertical,to ensure penetration of the pectoral muscleand the deep fascia; 7.5–10.0 ml of local analgesicsolution is injected. To facilitate insertion of theneedle to the proper depth it is best first to inducean insensitive skin weal.The indications for blocking the median nervealone are limited, for the surface area desensitizedis little more than that obtained with medial palmarblock (see Figs 11.4 and 11.5).Ulnar nerveThis nerve may be blocked by injection of 10 ml oflocal analgesic solution in the centre of the caudalaspect of the limb, about 10 cm proximal to theaccessory carpal bone, in the groove between thetendons of the ulnaris lateralis and flexor carpiulnaris, and beneath the deep fascia.Musculocutaneous nerveThis nerve is blocked on the medial aspect of thelimb where it lies on the surface of the radiushalfway between the elbow and carpus, immedi-

THE HORSE 263ately adjacent to the cephalic vein. At this site, itcan easily be palpated just cranial to the cephalicvein and blocked by the injection of 10 ml of localanalgesic solution.The complete desensitization of the distalhindlimbThe technique of nerve block of the hindlimbsometimes works extremely well but is unreliable,especially for removal of cutaneous sensation(Westhues & Fristch, 1960). Westhues and Fristchdescribed techniques for blocking the tibial andperoneal (fibular) nerves.Tibial nerveInjection is made about 1.5 cm above the point ofthe tarsus, in the groove between the gastrocnemiusand the deep digital flexor tendons.Palpation of the nerve at this site is facilitated byholding up the foot and slightly flexing the leg,although the injection is best made with the limbbearing weight. Care must be taken to inject deepto the subcutaneous fascia or only the superficialbranch of the nerve will be affected. Some 20 ml oflocal analgesic solution should be injected at thissite through a 2.5 cm, 20 gauge (0.9 mm) needlethat has been placed beneath the fascia.FIG.11.6 Sites for injection about the peroneal nerve onthe lateral aspect and the tibial nerve on the medial aspectof the horse’s hindlimb.proximal to the tibiotarsal joint will effectivelyblock the saphenous nerve.Block of the tibial nerve above the hock, and ofthe deep peroneal (fibular) nerve, desensitizes theplantar metatarsus, the medial and lateral aspects ofthe fetlock and whole digit. To produce a completeblock distal to the hock, these two nerves must beinjected together with the saphenous nerve, thesuperficial peroneal (fibular) nerve and the caudalcutaneous nerve (a branch of the tibial nerve).Peroneal (fibular) nerveThe superficial and deep branches of this nerveare best blocked simultaneously in the groovebetween the tendons of the long and lateral digitalextensors about 10 cm proximal to the lateralmalleolus of the tibia. First a 3.75 cm, 22 gauge(0.7mm) needle is introduced subcutaneously and10 ml of the local analgesic solution injectedthrough it to block the superficial nerve. Theneedle must then be inserted another 2–3 cm topenetrate the deep fascia and about 1.0–1.5 ml oflocal analgesic solution injected (Fig. 11.6) aroundthe deep branch.Saphenous nerveThe deposition of 5 ml of local analgesic solutionon the dorsal aspect of the median saphenous veinAccidents and complicationsSudden movement by the animal, while insertingthe needle or during injection, may cause the shaftof the needle to break from the hub. The accident isespecially liable to occur if an attempt is made tocarry out the operation without sedating or twitchinga nervous or fractious animal. A sufficientlength of needle may remain exposed for it to begripped with forceps and withdrawn. Removalwill be facilitated by raising the limb, and thus easingthe tension of the skin. Should the needle becompletely buried, it is necessary to insert anotherneedle into the subcutaneous connective tissue,provoke an insensitive weal, and make an incision1 cm or so long, directly over the broken needle toexpose it.Although horses can perform fast work aftersurgical neurectomy, care should be taken that a

264 ANAESTHESIA OF THE SPECIEShorse under the influence of palmar/plantar blockis not exercised vigorously, for incoordinate movementafter acute loss of sensation may result inbone fracture. (Cases involving the proximal anddistal phalanges were reported by J. G. Wright inthe 1st edition of this book.)Local analgesia for castrationThere are three methods in common use for desensitizingthe scrotum, testicle and spermatic cord byinjection of local analgesics but for all of them it isessential that the animal is properly restrained orsedated if the operator is not to be injured whencarrying them out on the standing animal. The animalis placed with its right side against a wall orpartition and if not sedated a twitch is applied toits upper lip. After preparation of the skin of thescrotum, prepuce and medial aspect of the thighs,the operator stands with his left shoulder pressedlightly against the caudal part of the animal’s leftchest wall. The neck of the scrotum on the rightside is gripped with the left hand and the testicledrawn well down until the skin of the scrotum istense (Fig. 11.7).Method 1A 19 gauge (1.1 mm) needle is quickly thrust intothe substance of the testicle to a depth of 3–4 cmand 30–35 ml of 2% lignocaine injected. When anadequate amount of lignocaine has been injectedthe testicle feels firm. The procedure is repeatedfor the left testicle, and local analgesic solution isinjected along the median raphe of the scrotum.After about 10 minutes has elapsed castration canbe carried out painlessly.Method 2The spermatic cord is grasped with the fingers justabove the testicle and a 5 cm 19 gauge (1.1 mm)needle thrust into the subcutaneous tissues of thatregion. The needle is kept stationary to avoid penetrationof blood vessels and about 20 ml of 2% lignocaineinjected around each spermatic cord. Thescrotal skin is injected along the line of the proposedincisions. This method does not seem aseffective as the one described above.FIG.11.7 Injection into the substance of the testiclesafter linear infiltration of the scrotal tissues.Method 3A long (12–15 cm) 19 gauge (1.1 mm) needle isthrust through the testicle and directed into thespermatic cord while 20–25 ml 2% lignocaine arebeing injected. After treatment of both spermaticcords the scrotal skin is infiltrated.To infiltrate the scrotal skin it is important that thedirection of the needle shall be almost parallel to theskin to ensure that its point lies in the subcutaneousconnective tissue, for if it enters the dartos or thesubstance of the testicle itself, difficulty may beexperienced in injecting the solution and, what ismore important, the skin does not become analgesic.The animal usually moves as the needle isinserted and the operator must be prepared for this.Some right-handed operators prefer to stand onthe right side of the horse, with the left hand holdingthe scrotum or spermatic cord, so that the leftarm is against the stifle and affords some measureof protection against a kick. The person holding

THE HORSE 265the twitch should stand on the same side as theoperator. It is interesting to note that many equinepractitioners assert that a twitch applied aroundthe upper lip appears to produce some measure ofanalgesia and is not simply a distraction or counterirritant.It may be relevant that the midpoint in themidline between the upper lip and the nose is, infact, a well-recognized acupuncture point.PARAVERTEBRAL ANALGESIAFIG.11.8 Location of the site for paravertebral block ofL2. A line extended vertically upward from the mostcaudal point of the last rib passes over the transverseprocess of L3. A needle inserted 3–6cm (depending onsize of the horse) from the midline over L3 should strikethe transverse process; L2 nerve can be located byredirecting the needle to pass anterior to the process.A thoracolumbar paravertebral block of T18, L1and L2 segmental nerves provides useful anaesthesiaof skin, muscles and peritoneum of theparalumbar fossa, and it is an excellent method ofanalgesia for procedures such as flank laparotomyor for laparoscopy in the standing horse (Fig. 11.8)(Moon & Suter, 1993). L3 should not be blocked, asin horses it provides some innervation to the hindlimbs, and its block may cause ataxia.The basic anatomy of the spinal nerves resemblesthat of cattle, each nerve bifurcating shortlyafter leaving the spinal canal, the dorsal branchsupplying the skin and superficial tissues, whilstthe ventral branch passes beneath the inter-transverseligament, and innervates the muscle layersand peritoneum. Thus, as with cattle, it is necessaryto block both dorsal and ventral branches ofeach spinal nerve if adequate analgesia is to beobtained. In cattle the landmarks for injection arefound by palpation of the transverse process of thelumbar vertebrae, but these are almost impossibleto locate in horses. However, Moon and Suter(1993) point out that a line from the most caudalportion of the last rib (easily located in almost allhorses) and perpendicular to the long axis of thespine passes across the transverse process of L3.Thus, to block the spinal nerve L2, the site chosenis over the transverse process of L3, and approximately5–6 cm lateral to the midline. A small bleb oflocal anaesthetic is placed in the skin, then 5 ml of2% lignocaine (or other suitable local analgesicagent) infiltrated in the muscle. A long spinal needle(eg. 18 G × 7–15 cm) is then introduced verticallyuntil it impinges on the transverse process; it iswithdrawn a little, then redirected slightly cranially,until the inter-transverse ligament betweenL2 and L3 is penetrated (felt as an increase, thensudden decrease, in resistance). Following aspirationto ensure that the needle is not in a blood vessel,20 mls of 2% lignocaine is slowly infiltrated,half 2.5 cm below the inter-transverse ligament,and the remainder 2.5 cm above to block the dorsalbranch of the nerve. Skarda (1996) points out that itis easy to enter the peritoneum and that this isdetected by a loss of resistance (as it penetrates thetransverse ligament) and sometimes by hearing airbeing aspirated through the needle. Should thishappen, the needle should be withdrawn to aretroperitoneal position, before the local anaestheticis deposited. The procedure is repeated toblock nerves L1 and T13. The sites for injection arelocated by measuring 5–6 cm anterior from theprevious site (less in ponies), and confirmed bythe needle impinging on a transverse process ofthe vertebrae.With practice, the technique is simple and reliable,although on occasions analgesia of the ventralarea of the paralumbar fossa is inadequate forsurgery, and local infiltration become necessary.EPIDURAL ANALGESIACaudal and more anterior blocksIn horses the caudal epidural block is performedby entering between the first and second coccygealvertebrae (Fig. 11.9), the spinal cord and its

266 ANAESTHESIA OF THE SPECIESmeninges ending in the midsacral region. Thedepression between the first and second coccygealdorsal spinous processes can usually be felt withthe finger when the tail is raised, even in the heavybreeds, about 2.5 cm cranial to the commencementof the tail hairs, although in fat animals it may beimpossible to detect any of the sacral or coccygealdorsal spinous processes. Upward flexion at thesacrococcygeal articulation is seldom discernible;in fact, in many animals this joint is fused A linedrawn over the back joining the two coxofemoraljoints crosses the midline at the level of the sacrococcygealjoint. Immediately behind this may bepalpated the dorsal spinous process of the firstcoccygeal bone, and the site for insertion of theneedle is the space immediately caudal to this. Theinterarcual space is smaller than in the ox and maybe more difficult to locate with the needle, particularlyin welldeveloped or fat animals in which theroot of the tail is well covered by muscle or fat.Sometimes it is possible to detect a ‘popping’ sensationas the interarcual ligament is penetrated. Thesurest evidence, however, that the canal has beenentered is the almost complete absence of resistanceto injection of the local analgesic solution.Most anaesthetists introduce the needle at rightangles to the general contour of the croup until thefloor of the neural canal is struck, but in the methodof Browne the point of the needle is inserted at thecaudal part of the intercoccygeal depression anddirected cranioventrally at an angle of 30 ° from thehorizontal so that its point will glide along thefloor of the neural canal and the needle can beinserted to its full length (the steep cranioventraldirection of the canal at this point allows this). It isprobable, however, that the first method, wherebythe needle is inserted at a 60 ° angle from the horizontal,is easier to perform. Where it is likely that acaudal block will need extending in duration, acatheter can be placed through the needle and intothe epidural space. An 18 G Tuohy needle may beplaced as described above, and a 20 G epiduralcatheter advanced through this. Whichever type ofneedle is used, the skin and subcutaneous tissuesshould be made insensitive by the injection of asmall weal of local analgesic solution.Ten millilitres of 2% lignocaine or 5 ml of 2%mepivacine, with or without a vasoconstrictor, isusually sufficient to produce caudal block in thelargest of horses. Analgesia takes much longer todevelop than in cattle and unless allowance ismade for this it may be erroneously concluded thatinjection was not made correctly. Analgesia willusually be present after about 20 minutes and persistsfor 35–50 minutes depending on whether ornot the solution used contained a vasoconstrictor.Caudal block is indicated to overcome strainingduring manipulative correction of the simplerforms of malpresentation of the fetus, for amputationof the tail (an operation which in the UK mayonly be performed for surgical reasons), and foroperations about the anus, perineum and vulva,suture of wounds, operation for prolapsed rectumand Caslick’s operation for vaginal wind sucking.Anterior blockABFIG.11.9 Caudal epidural block in the horse.The needlemay be inserted at right angles to the skin surface betweenthe first and second caudal vertebrae (B),or it may beintroduced further caudally over the cranial boder of thesecond coccygeal vertebra and inclined at an angle of about30° to the horizontal to advance up the neural canal (A).Local anaesthetic agents injected epidurally at thecaudal region in doses sufficient to cause anteriorepidural block have no place in equine anaesthesiabecause of the hindlimb paralysis produced.However, with modern epidural catheters, anteriorblock is technically possible to perform; smallquantities of local anaesthetic agents beingdeposited in the region of the dermatomes to beanaesthetized. Catheters inserted in the coccygealregion may be advanced at least as far forward asthe lumbosacral junction (Sysel et al., 1996). The

THE HORSE 267technique has been used to provide long termanalgesia with agents other than local anaestheticdrugs, which reduces the danger of unwantedhindlimb weakness.Subarachnoid anaesthesiaSubarachnoid catheterization in the horse is practicable(Skarda, 1996), and enables segmentalanalgesia to be provided if the catheter, inserted atthe lumbosacral junction, is advanced until itreaches the required dermatome. However, thetechnique is complicated, and paravertebral thoracolumbaranalgesia is usually preferable for surgicalanalgesia of the sublumbar region.domestic animal. In particular, cardiopulmonarydysfunction, nerve and ischaemic muscle damageappear more pronounced and can be difficult toavoid. The problems are often inter-related andseem to follow directly from the actions of theanaesthetic agents themselves, or from interferencewith mechanisms existing in conscioushorses to compensate for respiratory or cardiovascularchanges induced by recumbency. Otherproblems relate to the horse’s size, its temperamentand its tendency to panic. It is necessary toanticipate the problems from the beginning of theanaesthetic protocol in order to take action necessaryto avoid or reduce them; hence they will beconsidered in general at this stage.Use of other agentsThe use of morphine (p.257) and α 2 adrenoceptoragonists (p.252) by epidural injection has been discussedabove. Where such agents are required togive surgical analgesia it is usual to combine themwith small doses of local analgesics. The aim ofsuch combinations is to combine the rapid onset oflocal analgesics with the prolonged pain relievingproperties of opioids and α 2 adrenoceptor agonists,to reduce the dose of any single agent to below thatwhich may cause systemic effects and, hopefully, toreduce the dose of local analgesics to that whichwill not cause ataxia or hindlimb paralysis.The combination most commonly used is thatof xylazine and lignocaine (Grubb et al., 1992) butmany similar combinations have been employed.Opioids have also been combined with local analgesics.Butorphanol (0.04 mg/kg) and lignocaine(0.25 mg/kg) given into the epidural space hasbeen reported to give prolonged analgesia withoutthe horses showing ataxia (Farney et al., 1991).However, it must be remembered that only preservative-freesolutions should be administered intothe epidural space – morphine and xylazine areeasily obtainable in this form, hence their popularityfor use by this route.GENERAL ANAESTHESIAGeneral anaesthesia in horses appears beset withmore problems than are encountered in any otherPROBLEMS RELATING TO SIZE ANDTEMPERAMENTWhen handling horses the safety not only of thehorse, but also of the handlers must be considered,and methods of control used must reflect the temperamentof the horse and availability of welltrained personnel. Sedative premedication aidsplacement of catheters and the smoothness ofinduction of anaesthesia. The sheer weight andbulk of a large horse makes it difficult to handle,transport or position for surgery without adequatemanpower or mechanical aids. Many unconscioushorses are transported for short distances (e.g.from the operating table to recovery box) suspendedin a net or by their hobbled legs from anoverhead hoist. Other methods of moving unconscioushorses include trolleys which may constitutethe floor of the anaesthetic induction box andmay then become the operating table top.In clinical practice anaesthesia in the adulthorse is amost always induced by i.v. agents,although in young foals it may be induced withinhalation agents. Breed is often allied to temperamentand must not be ignored in the selection of ananaesthetic technique. A method suitable for aphlegmatic warmblood, trotter or quarter horsemay be totally unsuitable for a very excitableyoung Thoroughbred or Arab.Ideally the horse should regain its feet as rapidlyas possible at the first attempt, with minimal ataxia.Unfortunately this is not easily achieved followingprolonged anaesthesia. Although prolonged

268 ANAESTHESIA OF THE SPECIESrecumbency is not desirable, it is now appreciatedthat in some cases ultra-fast recoveries may be ofpoor quality because the horse tries to arise whilststill disorientated. The best quality recoveries areseen where the drugs given during anaesthesia areeliminated in such a manner that the horse doesnot try to rise until it is ready, and it may be necessaryto use sedation to increase the duration ofrecumbency. Animals which are unused to peoplemay try to rise too soon, but the young, well handledbut excitable Thoroughbred colt (whichrequires very careful handling for induction ofanaesthesia) often remains recumbent for a considerabletime, and then recovers remarkably well.Ponies exhibit poor quality recovery as often as dolarge horses, but it is the heavier animal which ismost likely to suffer from serious injury as a result.Other causes of poor quality of recovery fromanaesthesia include nerve and muscle damageinduced during anaesthesia, and untreated postoperativepain.DISTURBANCES IN CARDIOPULMONARYFUNCTIONDisturbances of cardiopulmonary function havelong been recognized in anaesthetized horses but,in spite of much research, their cause remainsuncertain. Because general anaesthesia necessarilyinvolves recumbency there has been some debateas to the relative importance of the roles of recumbencyand of anaesthetic agents in their genesis,but in conscious experimental animals the cardiopulmonarydisturbances produced by lateralrecumbency have been found to be minimal (Hall1984; Ruch et al., 1984). The effects of posture cannotbe ignored for disturbances are more severefollowing supine rather than lateral recumbency inanaesthetized horses; however it is probable thatwhile various postures may magnify effects theydo not initiate them.From the evidence available today it seemslikely that any disturbances resulting from recumbencyare minimized in conscious animals by theoperation of compensatory mechanisms that failor become depressed when an anaesthetic isadministered. Their failure or depression is manifestedin several ways but probably the mostimportant results which affect equine anaestheticmorbidity and mortality are cardiovasculardepression, the development of a large alveolar–arterial oxygen tension gradient ((A–a) PO 2 ) and,probably resulting from the first two factors,postanaesthetic myopathy.Cardiovascular effectsHorses in which anaesthesia is maintained usingvolatile anaesthetic agents often suffer fromhypotension, which may be the result of vasodilationand/or a fall in CO. A number of studies haveinvestigated the effects of volatile anaestheticsalone, i.e. including volatile anaesthetic induction(Steffey & Howland, 1978a; Dunlop et al., 1987;Steffey et al., 1987a, b, c; 1990; 1993). These investigationshave demonstrated that halothanedepresses the equine heart in a dose-dependentfashion. Accommodation occurs and, at a givenend-tidal concentration, CO and heart rate rise asanaesthesia progresses, possibly due to the releaseof catecholamines, although the cause of thisrelease remains uncertain. The time course of thisaccommodation is more prolonged (over five ormore hours) than would be encountered duringnormal clinical practice. Accommodation is morepronounced in spontaneously breathing animals,probably as a result of hypercapnia. Anaesthesiawith isoflurane or sevoflurane (Steffey &Howland, 1980; Aida et al., 1996) also results inhypotension, mainly arising from vasodilation as,at eqi-MAC values, CO is better maintained thanwith halothane. However, even with these neweragents increasing the concentration still results in adose related fall in CO.Such experiments as detailed above provideuseful pharmacological information about thevolatile anaesthetic agents in horses, but are nottypical of normal clinical anaesthetic practice, inwhich anaesthesia is induced by i.v. agents. Withthe i.v. techniques most commonly employed, theintroduction of the volatile anaesthetic agentresults in marked hypotension, in experimentalsituations mean arterial blood pressure (MAP) frequentlyfalling to below 40 mmHg (Gleed &Dobson, 1990; Lee et al., 1998a). With halothane,these minimal levels are reached 30–40 minutesafter anaesthetic induction, and are considerablylower than the minimal MAP of 70–80 mm Hg

THE HORSE 269which occurred with 1 MAC in most of the experimentalstudies in which halothane was used as asole agent. ABP slowly rises through vasoconstrictionover the next hour, but CO remainsunchanged or may even fall. Similar changes inMAP also occur with other volatile anaesthetics,although with these newer agents CO is bettermaintained. The relative effects of the different i.v.anaesthetic techniques on the subsequent cardiovascularactions of the volatile anaesthetic agentshave not been fully investigated, but the fact thatan induction technique itself does not cause cardiovasculardepression does not mean that itscombination with a volatile agent will not do so.With many total i.v. techniques, blood pressure iswell maintained, but this does not mean that thereis no cardiovascular depression.In clinical practice, although hypotension mayoccur it is rarely as severe as that seen experimentally,as surgical stimulation causes APB to rise.However, this rise is due to vasoconstriction, andCO may fall, probably because of the increasedafterload (Wagner et al., 1992). To maintain bloodflow an adequate perfusion pressure must be coupledwith good CO, and unfortunately CO currentlyis not easy to measure. Pink mucousmembranes and a rapid capillary refill time indicategood peripheral blood flow. Venous blood oxygenvalues also give a guide as to the adequacy ofperfusion. Although, ideally, mixed venous samplesare necessary, in the horse the oxygen tensionof jugular venous blood approximates (Wetmore etal., 1987) and values above 5 kPa (37.5 mmHg)indicate the adequacy of oygenation and thereforeof perfusion of the peripheral tissue.Pulmonary changesA major problem encountered in equine anaesthesiais that the arterial oxygen tension (PaO 2 ) isalways much lower than might be expected fromthe inspired oxygen tensions (PiO 2 ), i.e. there is alarge (A–a)PaO 2 . A normal (A–a) of about 18mmHg (2.4 kPa) in standing horses breathing air isdoubled in anaesthetized, laterally recumbent animals.Most investigations concerned with(A–a)PO 2 gradients have been carried out underhalothane/oxygen anaesthesia but similar differenceshave been found during general anaesthesiawith other agents. The increased (A–a)PO 2 may bethe result of a combination of several factors andthese have been the subject of many investigationsin recent years.The PaO 2 depends on the size of the animal andits position during anaesthesia (Hall, 1983), but itis relatively unaffected by the degree of respiratorydepression produced by the anaesthetic agent.Many studies have reported relative or absolutedecreases in PaO 2 with or without increasedPaCO 2 levels. Moreover, there has been shown tobe no statistically significant difference in(A–a)PO 2 in a series of animals anaesthetized oncewith spontaneous breathing and on another occasionwith IPPV to normocapnia (Hall et al., 1968a,b). One notable feature is that the (A–a)PO 2 gradientdoes not increase significantly with time(Gillespie et al., 1969).When a horse is disconnected from a breathingcircuit containing an O 2 -rich mixture of gases andallowed to breathe air, PaO 2 of around 50 mmHg(6.5 kPa) is common. This may represent a bloodO 2 saturation of around 90% (Clerbaux et al., 1986)but the steep part of the dissociation curve startsabout here and any accident such as temporaryobstruction of the airway can have very seriousconsequences. It is not uncommon for frankcyanosis to be observed in the recovery period ifoxygen is not administered but it must be rememberedthat the PaO 2 may fall to 40 mmHg (5.3 kPa)without cyanosis becoming apparent if the bloodflow to the mucous membranes is adequate. Toimprove the situation O 2 must be insufflated at aminimum rate of 15 l/min. The PaO 2 apparentlyrecovers to normal levels as soon as the animalregains its feet.Factors other than hypoventilation which maycontribute to the large (A-a)PO 2 include diffusiondefects in the lungs, right-to-left intrapulmonaryvascular shunts, mismatching of ventilation andperfusion in the lungs, atelectasis and a fall in COwithout a corresponding fall in tissue oxygen consumption.Diffusion impairmentThere is no evidence that diffusion impairmentoccurs so this must be regarded as an unlikelycause of hypoxaemia.

270 ANAESTHESIA OF THE SPECIESFIG.11.10 Slices of the lungs of a large horse that diedfollowing anaesthesia.The horse had undergone 3 hours ofsurgery in dorsal decubitus,then been placed in lateraldecubitus for recovery. The lung dependent during lateraldecubitus (lower picture) shows a large region of totalcollapse,while the lung which was uppermost in recoverystill shows considerable areas of collapse around the hilarregion from the period of time in which the horse was indorsal decubitus.AtelectasisProgressive atelectasis is unlikely because inhorses the (A-a)PO 2 develops very soon after theinduction of anaesthesia and thereafter remainsrelatively constant. There is no doubt, however,that atelectasis does occur for total collapse ofregions of the dependent lung is commonly seen atautopsy of horses dying while anaesthetized(Fig. 11.10). This collapse is presumably due tocompression of the lung by overlying abdominaland thoracic viscera. A totally collapsed lung actsas a venous–arterial shunt and can cause markedarterial hypoxaemia. A shunt of 15% of the totalpulmonary blood flow has been found in laterallyFIG.11.11 Opacity of the lower lung seen in aradiograph taken at full expiration after 20 minutes ofhalothane anaesthesia in right decubitus (fromMcDonell,W.N.,Hall,L.W & Jeffcott,L.B.(1979),withpermission).recumbent horses under halothane anaesthesia,compared with about 5% in the standing animal(Gillespie et al., 1969). Decrease in lung volumeshort of collapse may not have all that an adverseeffect on alveolar ventilation for the alveolar compliancecurve predicts that a small alveolus willexpand proportionally more for any given changein intra-alveolar pressure.Radiographic studies (McDonell et al., 1979)and blood samples drawn from pulmonary veinsthrough implanted catheters in conscious andanaesthetized animals in lateral decubitus (Hallet al., 1968b; Hall, 1979) have afforded further confirmationof the impairment of function in thelower lung. Radiographic appearances (Fig. 11.11)are suggestive of a greatly reduced volume of thelower lung in laterally recumbent animals(McDonell et al., 1979; Nyman et al., 1990). When ahorse lies on its side a diffuse radiographic opacityof the lower lung develops within 20 minutes and

THE HORSE 271may be due to alveolar collapse, regional pulmonarycongestion and/or interstitial oedema.Spontaneous deep breaths or forced expansion ofthe lung by compression of an anaesthetic reservoirbag, both of which might be expected toreexpand collapsed alveoli, fail to alter the radiologicalappearance. Stolk (1979) demonstrated nosignificant increase in the water content of thelower lung and considered that the radiographicopacity must be due to an increased blood content.The opacity persists for some time after the horseis turned over and this raises the possibility thatvenous congestion may kink pulmonary veins andhinder the prompt drainage of blood from theaffected lung.Venous admixtureIt would seem unlikely that total collapse of lungregions resulting in right-to-left vascular shuntingaccounts for all the venous admixture whichoccurs in anaesthetized horses. A substantialamount must be due to the occurrence of grossmismatching of ventilation and perfusion in thelungs. Some indication of this may be obtainedfrom the physiological deadspace:tidal volumeratio. In most mammals this ratio is about 0.3 butin anaesthetized horses it is over 0.5 (Hall et al.,1968a).The large physiological deadspace: tidal volumeratio probably explains why IPPV is relativelyineffective in decreasing the (A–a)PO 2 in horses.The augmented tidal volume resulting from IPPVmerely increases ventilation to those regions of thelung which are already overventilated in relationto their perfusion, i.e. those contributing to thephysiological deadspace. While even in horses theincreased ventilation will remove carbon dioxidefrom the lungs and keep the PaCO 2 within normallimits, it will not greatly increase the PaO 2 .Effect of cardiac outputCO is usually reduced under anaesthesia but tissueO 2 consumption may remain substantiallyunchanged. The resulting arterio-mixed venousPaO 2 tension difference, (A–V)PO 2 , thus increasesand venous blood passing through the anatomicalshunt or regions of lung collapse has a greatereffect on the (A–V)PO 2 . It is important to note herethat the magnitude of the reduction in CO cannotbe inferred from the ABP and that IPPV mayreduce CO. Indeed, the oxygen tension in mixedvenous blood from the pulmonary artery (PvO 2 ) islower when IPPV is used despite a slight increasein PaO 2 , presumably because of an increasedextraction of oxygen from the blood by the tissue –necessitated by the reduced CO – and hence rate oftissue perfusion. Because right-to-left intrapulmonaryshunt increases from the normal 5% in thestanding, awake horse to about 15% underhalothane anaesthesia (Gillespie et al., 1969),the effect of the shunted blood of lower thannormal PO 2 will be to produce noticeable reductionin the mixed PaO 2 of the blood in the leftatrium (PaO 2 ).Lung volumeThe larger the lung the greater the stretch acrossthe airways and the less tendency for closure tooccur on expiration. The lung volume at which airwayclosure starts to occur (‘the closing volume’) isimportant, for, if airways close, gas trapped distalto the point of closure soon becomes depleted ofoxygen and the blood perfusing the region getsthrough unoxygenated to join the blood fromother regions and reduces the mixed PaO 2 . Studiesstrongly suggest that during general anaesthesiathe horse’s lung volume is reduced to a level atwhich airway closure may occur and that thereduction in lung volume in the laterally recumbenthorse was not equally distributed betweenthe lower and upper lungs (McDonell, 1974). Inboth right and left lateral decubitus there was agreater reduction in the volume of the lower lung,and pulling the legs together in hobbles reducedlung volume still further.The effect of airway closure on PaO 2 might bemitigated by collateral ventilation from neighbouringalveoli but although anatomical studies(Tyler et al., 1971) indicate that this is possible, it isunlikely to occur in horses. McDonell (1974) concludedthat recumbency rather than anaesthesiawas responsible for the reduction of lung volumefound in anaesthetized ponies but more recentwork has suggested that the anaesthetic agent mayalso play a part (Watney et al., 1987).

272 ANAESTHESIA OF THE SPECIESConfirmation of serious impairment of expansionof the lowermost lung has been obtained fromhistological examination of very rapidly frozenlung regions. Also, from the histological appearancesit would seem that a reduction of the tetheringeffect of lung parenchyma on extra-alveolarvessels might well be responsible for the increasedresistance to blood flow in this lung (Hall, 1979).It might be thought that increasing the airwaypressure to above atmospheric pressure (positiveend-expiratory pressure or PEEP) will, by increasingthe lung volume to an amount equal to theproduct of the total compliance and the pressure,decrease the tendency for airways to close andthus raise the PaO 2 . However, the imposition of a10 and 20 cmH 2 O (1 and 2 kPa) expiratory resistanceby the insertion of a water trap in the expiratorylimb of a circle absorber fails to improve thePaO 2 in horses breathing spontaneously underhalothane/oxygen anaesthesia (Hall & Trim, 1975),and indeed usually produced immediate respiratoryarrest. Broadly similar results were obtained inhorses under barbiturate /guaiphenesin anaesthesia(Beadle et al., 1975), but in this second studyarterial oxygen saturation was always over 95%. Itis possible that some beneficial effect of expiratoryresistance might be found where arterial oxygensaturation is reduced by pulmonary disease, but itseems likely that, because of its dome-like shape,only the upper part of the horse’s diaphragm issusceptible to displacement by end-expiratorypressure, and thus lung volume will only increasein regions which are already well ventilated. Theindiscriminate use of end-expiratory pressure certainlyhas no place in routine equine anaesthesiaand, by reducing CO, it may even be harmful insome circumstances.Pharmacological treatmentsHypoventilation is not the major cause of anaesthetic-inducedhypoxia in the horse, and indeed inthis species hypoxia, rather than hypercapniaappears to be the respiratory drive under anaesthesia(Schatzmann, 1982; Steffey et al., 1992). Thusit is not surprising that respiratory stimulantssuch as doxapram are ineffective at improvingoxygenation in anaesthetized horses (Taylor,1990). Gleed and Dobson (1990) reported that theβ 2 agonist clenbuterol (0.8 mg/kg) was very effectivein increasing PaO 2 in dorsally recumbenthalothane anaesthetized horses and their workwas confirmed in clinical cases (Keegan et al.,1991). Other studies failed to reproduce theseFIG.11.12 Postanaesthetic myopathy shown in the forelimb.Characteristic posture of pain with head thrown back andup when made to walk.In this case there was hard swelling of the shoulder muscles and triceps.The posture due to painvaries with the muscles involved.

THE HORSE 273results (Doddam et al., 1993; Lee et al., 1998b) and itis probable that both positioning and the anaesthetictechnique employed influence the efficacy ofclenbuterol in raising PaO 2 . In some cases theinjection of clenbuterol is followed by a transientfall in PaO 2 , presumably because of the increasedO 2 demand associated with the side effects ofsweating and tachycardia. Thus the routine use ofclenbuterol to increase PaO 2 in anaesthetizedhorses cannot be recommended for use in clinicalpractice.Muscle and nerve damageThere is an incidence of up to 6.4% of lameness followinganaesthesia in the horse (Klein,1978;Richey et al, 1990), much of which is due to damageto nerves and muscles during recumbency. In theclinical situation it is not always easy to distingishbetween the two syndromes (hence the term‘radial paralysis’ was once used to describe thecondition now known to be caused by a tricepsmyopathy (Fig 11.12) and it is probable that it somecases both occur together.Postanaesthetic myopathy (rhabdomyolysis)It is now generally accepted that the common formof postanaesthetic myopathy is due to muscleischaemia caused by inadequate muscle perfusion(Trim & Mason, 1973; Lindsay et al., 1980; 1985;1989). Clinical surveys (Klein, 1978; Richey et al.,1990) have demonstrated that the incidence of thecondition is increased by duration of anaesthesiaand by periods of hypotension. In experimentalcircumstances it can be can be induced by prolonged(three plus hours) of hypotensive anaesthesia(Grandy et al., 1987; Lindsay et al., 1989). Thefailure of perfusion to the muscles is a typical‘compartmental syndrome’. i.e. increased pressurewithin the space limited by the fascial sheath of themuscle compromises the circulation. When intracompartmentalmuscular pressure increases to thepoint at which the local circulation fails, the musclewill become ischaemic. Damage will occur atreperfusion and this results in swelling and a furtherincrease in compartmental pressure, thusworsening the situation. The potential for continuingdamage at reperfusion (Serteyn et al., 1990)explains why horses may appear unaffected whenthey first rise, the condition becoming apparentover the ensuing hours.In order to limit the occurrence of myopathy,three factors are necessary:(a) The time of anaesthesia should be kept asshort as possible and anaesthetic time shouldnever be wasted.(b) Intracompartmental pressure should bereduced to the minimum. The intracompartmentalpressure in the triceps muscles of the dependentlimb in a horse positioned on a hard surface mayreach as high as 50 mm Hg; positioning on a softsurface reduces this (Lindsay et al., 1980; 1985).However, the weight of a horse or of one of itslimbs can compress veins while patent arteriesallow blood to flow into muscle capillaries, thusresulting in a rapid increase in intracompartmentalpressure to that of arterial pressure (Taylor& Young, 1990) and the total failure of all muscleperfusion; this is probably the reason for myopathyin the non-dependant (or upper ) limbs oflaterally recumbent horses.(c) Blood supply to the muscles should beincreased. It has been routine to assume thatthis means increasing ABP, and certainly it isnecessary to raise this above the ‘closing pressure’within the muscle compartment. However,once ABP is above this ‘closing pressure’, thenfurther improvement in muscle blood flow dependson increasing CO (Lee et al., 1998a,b,c).Positive inotropes such as dobutamine improveCO, ABP and muscle blood flow whilst vasoconstrictoragents increase ABP but have no actionon peripheral perfusion (Fig 11.13).The condition described above fails to explainall cases of myopathy, and it is probable thatthe condition is multifactorial. Klein (1978) consideredthat there were two distinct types of anaestheticinduced myopathy, the compartmentalsyndrome and a more generalized form whichshe considered was more likely to occur in veryfit animals; the authors have seen two cases ofacute generalized rhabdomyolysis occurring inhorses one–two days after anaesthesia, in whichpost-mortem findings resembled capture myopathy.The condition has much in common withequine azoturia. It has been postulated that the

274 ANAESTHESIA OF THE SPECIESMean arterial blood pressure(mmHg)Cardiac index(l/min/m 2 )Intramuscular blood flow(% change from time 0)120 Mean arterialblood pressure100806040200–20 0 20 40 60 807 Cardiac index6543210–20 0 20 40 60 80400 Intramuscularblood flow300200100nutritional status and resulting intracellular pHat the time of anaesthesia is another factor involved,but no survey has found a significant linkbetween the animals’ nutritional status and anaesthetic-relatedmyopathy. It would appear the generalizedcondition is sporadic and unpredictablein occurrence.The treatment for myopathy is mainly symptomatic:analgesia (the condition is very painful), sedationif necessary, prevention of further damage,fluids (to prevent renal damage) and a great dealof tender loving care. As much of the damageoccurs at reperfusion there could be a role for theadministration of free radical scavengers, but asyet there is no evidence as to their efficacy. It isprobable that by the time the condition is diagnosed,the damage is already present.NeuropathyNerves may be damaged during the anaestheticprocess by the effects of pressure, of stretching,and by ischaemia. Peripheral neuropathies (suchas facial nerve damage through pressure from theheadcollar (Fig 11.14) are easy to diagnose, butother cases (e.g. femoral nerve damage) may be0–20 0 20 40 60 80Time (min)ControlDobutaminePhenylephrineFIG.11.13 Cardiac index,mean arterial blood pressure(MAP) and intramuscular blood flow in the dependenttriceps muscle in 6 halothane-anaesthetized ponies.Ondifferent occasions the ponies were given increasing dosesof infusions of one of the following: saline (control),phenylephrine or dobutamine.Dobutamine increased MAP,cardiac index and intramuscular blood flow,but whilstphenylephrine was equally effective in increasing MAP, itfailed to improve either cardiac index or intramuscularblood flow (adapted from Y.H.Lee,et al.,(1998)).FIG.11.14 Facial nerve paresis resulting from pressure.In this case the damage resulted from inadequate paddingon the operating table,but more typically it results frompressure exerted by a head collar.

THE HORSE 275difficult to differentiate from myopathy, andindeed it is probable that the two conditions frequentlyoccur concurrently. Neuropathy is notpainful, but if it involves the motor supply to morethan one limb, the horse will be unable to rise.Contused nerves may regain their function oncethe surrounding swelling has subsided, so symptomatictreatment should be combined with goodnursing.A very occasional but disastrous occurrence followinganaesthesia is spinal malacia. The problemhas only been reported to occur in young horsespositioned on their back for a short procedure.Most, but not all cases have occurred in heavyhorses (Brearley et al., 1986; Lam et al., 1995; Trim,1997). Sometimes the horse fails to regain its feetfollowing anaesthesia, other times it will stand, butan ascending paralysis commences. The conditionappears totally painless; many cases have beenmaintained by good nursing for several days butthe condition always progresses and euthanasiais inevitable. The cause of this condition isunknown.PREPARATION FOR GENERALANAESTHESIAThe preanaesthetic examination and the generalprinciples of preparation prior to anaesthesiadescribed in Chapter 1 are, of course, applicable tohorses, but there are some aspects of preanaestheticpreparation of these animals which warrantfurther consideration.General considerationsTo preserve the largest oxygen store in the bodyand to minimize gas trapping in the lungs, the FRCneeds to be maintained at the highest possiblelevel. Except in emergencies, it is always possibleto ensure that the animal is fasted before anaesthesia.Fasting for more than 18 hours may resultin acidosis, and is probably inadvisable, but itincreases the FRC by up to 30%, presumably dueto a reduction in the bulk of the abdominal contentsthrough loss of ingesta and reduced gas content(McDonell, 1974). Water should always beavailable except for the last two hours prior toanaesthesia.Extremely fit horses on high levels of nutrition,fed on grain-rich diets, and horses entirely grassfed seem particularly difficult to manage. Theyoften develop abdominal distension during anaesthesiaeven after careful fasting and there is a clinicalimpression, unsupported by investigationaldata, that they are more prone to develop circulatoryand other problems. Although there appears tobe little scientific justification for it, many experiencedanaesthetists and equine surgeons are firmbelievers in the old practice of ‘letting down’ ananimal before subjecting it to anaesthesia andoperation, i.e. reducing the protein and energycontent of its diet for some 7–10 days before anaesthesia.In the authors’ opinion, to postpone all butthe most urgent of operations until a horse whichis in full training has lost the peak of its fitnessfrom being fed a less rich diet certainly does noharm and may have much to commend it.Unfortunately, economic considerations oftendemand that horses be returned to full work withthe minimum of delay and this period of therapeuticinactivity is not well received by many owners.Shoes should be removed before anaesthesia, orat least covered with adhesive plaster, to preventdamage to flooring or the animal itself in therecovery period. Surgeons may request that thehorse receives prophylactic treatment for tetanusand is given antibiotics prior to the inductionanaesthesia. Many of the antibiotic agents mayinfluence the effects of anaesthetic drugs.Gentamycin and other antibiotics of this groupwill increase the length of action of neuromuscularblocking agents. The i.v. injection of penicillincauses marked hypotension (through vasodilation)for approximately 40 minutes (Hubbell et al.,1987) and is best avoided just prior to anaesthesia.As the cardiovascular effects of most antibioticsare unknown, their i.v. use immediately prior toanaesthesia should be avoided unless absolutelyessential to the overall success of the case.In emergencies the aim of preparation foranaesthesia is to improve the physical status of thehorse as much as possible, and to make any preparationswhich may reduce the risk of the perioperativeprocess. To detail all such preparations isbeyond the scope of this chapter. Briefly,orthopaedic cases may need support to the limb toprevent damage at anaesthetic induction, and

276 ANAESTHESIA OF THE SPECIESanalgesia and sedation should be chosen to avoidexcessive ataxia. Most acute thoracic crises are theresult of trauma and horses suffering from chestinjuries may be agitated, restless and dyspnoeic,and may require an analgesic both for its sake andto reduce the risk of injury to attendants. Providedexcessive doses are not used, the potential abilityof analgesics to produce respiratory depressioncan be ignored. Air and/or fluid should beremoved from the pleural cavity by the insertion ofa chest drain before general anaesthesia isinduced. In most emergency cases, hypovolaemianeeds to be corrected before induction of anaesthesia.However, where blood loss is acute and thepotential for further loss is still present (e.g. haemorrhagefrom the guttural pouch) such replacementshould be limited prior to anaestheticinduction as an increase in blood pressure mayresult in the commencement of severe and uncontrollablehaemorrhage. In such cases the agentsused for sedation and analgesia should have minimaleffects (in either direction) on blood pressure.Once the horse has been anaesthetized blood pressurewill almost certainly be reduced, and it maythen be necessary to administer rapidly high volumesof fluids.ColicThe most common equine emergency case presentedto the anaesthetist is that of colic. Mostcases of colic presented for surgical treatment havealready been treated medically and it is importantto consider the drugs used, their route of administration,doses and time of dosing, for they caninfluence the response to subsequent anaesthesia.Pain is usually indicative of gastric and/or intestinaldistension and of acute ischaemia. Its severitymay make the horse unmanageable until itbecomes utterly exhausted and pain must be controlled,although this is not always easy. NSAIDs,in particular flunixin, are widely used and can beso effective in reducing both the pain of colic andthe signs of toxaemia as to mask the need for surgery(Moore, 1994). Opioids which are often usedinclude butorphanol, pethidine (often in verylarge doses), methadone and morphine. Xylazineand detomidine are usually the most effectiveagents to provide analgesia in colic, but dosesshould be kept low both to limit their duration ofaction, and their cardiopulmonary effects in analready stressed horse. The effect of these agentson gut motility is probably unimportant as it iscomparatively short acting. Acepromazine, beingan α-adrenergic blocker, will contribute tohypotension in dehydrated or shocked animalsand is generally not advised if surgery will be necessary,although doses of up to 0.05 mg/kg areunlikely to do any harm.The main problem in the preanaesthetic preparationof most colic cases is the replacement offluids in the dehydrated and possibly shockedanimal. Fluid replacement is extremely urgent insurgical cases if any consistent measure of successis to be obtained. Unfortunately, diagnosis is veryimprecise, and there is an understandable reluctanceon the part of both owners and veterinariansto spend a considerable sum of money and time oncases which may at laparotomy prove to be inoperable.To overcome this reluctance some acceptableroutine which does not involve replacement of themajor part of the fluid deficit prior to anaesthesia isclearly desirable. Our experience of cases in whichtympany or violent intractable pain allowed onlyminimal preparation indicates that if really vigorousreplacement is carried out once the surgeon hasconfirmed that surgical treatment is possible, a successfuloutcome is quite as likely as in cases treatedbefore the induction of anaesthesia. Moreover, incases of intestinal obstruction many are of the opinionthat massive preoperative infusions are betteravoided since much of the fluid infused accumulatesin the obstructed intestine, making operationmore difficult and time consuming because of thegreater need for decompression of the bowel.Thus, it is possible that ‘minimal’ preparationcan be justified on both surgical and economicgrounds but it must be emphasized that for successit must be carried out in a rational manner.Whenever possible anaesthesia should not beinduced in a colic case until hypovolaemia hasbeen improved and the packed cell volume (PCV)decreased. Tachycardia may persist, due to pain ortoxaemia, even after the blood volume has beenrestored to normal. Hypertonic saline (4 ml/kg i.v.of 7.5%) followed by large quantities of Ringer’slactate provides an inexpensive method of treatingthe hypovolaemia rapidly. Other methods include

THE HORSE 277the transfusion of plasma or plasma substitutes,such as starch. Acid–base disturbances are seldoma problem in the preoperative period and there isno need to administer bicarbonate at this stage.The administration of bicarbonate intraoperativelyresults in a very high PaCO 2 , and the rapidexhaustion of the carbon dioxide absorbent of theanaesthetic circuit. Even in cases complicated byseptic shock, the routine administration of glucocorticoidsbefore operation is of doubtful value.Non-steroidal anti-inflammatory drugs (NSAIDs),if not already given, are usually administeredboth for their analgesic and antitoxaemic effects.Methods of treatment of endotoxic shock, such asthe use of antibodies are very expensive and as yetthere is no published data as to their efficacy inimproving overall success.Regardless of whether preoperative fluids areto be given to a colic case, at least one reliable i.v.line must be introduced into the jugular vein. Astomach tube should be passed through one nostrilbefore the horse is anaesthetized and the stomachdecompressed. It should be withdrawn intothe oesophagus before the induction of anaesthesiabecause if left in the stomach it seems to encourageregurgitation, but it should not be completely removedfor once the horse is recumbent underanaesthesia it is almost impossible to pass a tubedown the oesophagus to the stomach. Gastricdecompression will minimize the likelihood of thestomach rupturing during induction. Wheneverpossible the surgical site should be clipped and preparedwhile the animal is conscious and standing,for the duration of the anaesthetic period needs tobe kept to a minimum in these very ill animals.Mares nursing foals should not be separated fromtheir offspring in the preanaesthetic period. If it isnecessary to operate on the mare, the need forsedation is greatly reduced if anaesthesia isinduced in the presence of the foal. Similarly, thepresence of a foal’s sedated mother contributes tothe smooth induction of anaesthesia in the foal.It is always safer if the weight of the animal isknown and it should be determined by actualweighing, for visual appraisal, even with experience,is too inaccurate. Under field conditions it isimprobable that weighing facilities will be available,and the average figures given in Table 11.3constitute a useful guide. The weight of a horsemay also be estimated with acceptable accuracyfrom the formula:Weight (kg) =The girth is measured just behind the elbow andthe length is from the point of the shoulder to theline of the ischial tuberosity. M. Down and L. Gray(personal communication) weighed 400 horses ofall ages, including geldings, stallions and maresadmitted to the Cambridge Veterinary School overa 3-year period and found that the formula givenabove always estimated the weight to within 25 kgof the true weight. Commercially available ‘weighbands’base their calculation on the girth measurementonly, but still provide a useful estimate ofweight.Intravenous techniquesGirth (inches) 2 × Length (inches)660In horses i.v. injections are usually made into thejugular vein about half way down the neck. Thehorse should be handled quietly, as once forciblerestraint (such as the twitch) is used many willtense their neck muscles and obscure the jugularfurrow, making i.v. injection difficult and the dangerof accidental intracarotid injection more likely.The usual aseptic precautions should be takenprior to insertion of a needle or catheter, the size ofwhich depends on personal preference and onwhat is to be injected. A small fine needle (e.g.23 G) does not necessarily cause the horse less painTABLE 11.3 Ranges in weight for various types ofanimalType of animalWeight (kg)Children’s ponies 150–300Donkeys 150–200Thoroughbred yearlings 300–350Thoroughbred 2 y.o. 300–400Thoroughbred 3 y.o. 400–450Thoroughbred adults 450–550Hunter 450–675Warmbloods 500–750Cart yearlings 350–450Cart 2 y.o. 450–525Draught cross 550–625Heavy draught 650–850

278 ANAESTHESIA OF THE SPECIESthe point of injection and maintained there for atleast 5 minutes in order to prevent the formation ofa haematoma. Unfortunately intracarotid injectionmay not be recognized if a small bore needle isemployed. Once the needle is in situ, its hub andthe syringe should be held and pressed gently andcontinuously against the animal’s neck during anyinjection so that should the animal move its neckthe hand (and needle) will move with the horseand thus overcome any tendency for the needle tobe pulled out of the vein.Catheterization of the jugular veinFIG.11.15 Injection into the jugular vein of the horse.The vein is easily raised with digital pressure.‘Neck ropes’should not be employed for this purpose as they invariablydisplace the skin resulting in withdrawal of the needle orcatheter from the vein when their compression isreleased.than one of 19 G, but will reduce the damage to thevein which may be important if many such injectionsare anticipated. The vein is distended bypressing the thumb into the jugular furrow justbelow the site of venipuncture (Fig. 11.15). Thistenses the skin and the distended vein is easily palpable.Two methods of placement of a needle maybe used. In the first, the point of the needle isdirected at an angle of 45 ° to the vein, slid throughthe skin, into the vein then advanced up the veintowards the head. In the second method the needleis held at an angle of 90 ° to the vein, thrust into it,then turned 90 ° so that it can be advanced upthe vessel. It is important that a good length of needle(or catheter) is introduced into the vein otherwisethere is a risk that as the vein subsides, on therelease of pressure, it will retract away from theneedle or that the slightest movement will causethe needle to leave the vessel. A free flow of bloodindicates that the needle is well placed in thelumen of the vein. If only a few drops of bloodfall either (1) the needle is in a perivascularhaematoma or (2) the needle is in the vein but itslumen is partially blocked. If red blood spurts, orblood is very free flowing then the needle may bein the carotid artery and should be withdrawn, thefist being placed hard into the jugular furrow overIf larger needles or catheters are to be used in foals(which are hypersensitive to injections), or if theanimal is very sensitive, it is necessary to desensitizethe skin either by injecting a bleb of lignocainesubcutaneously via a very fine needle, or by usingan intradermal pressure injector. EMLA creamalso may be used for this purpose but it is difficultto keep the cream-covered swab in place for longenough to be effective.Catheters are now almost routine for theadministration of i.v. anaesthetic agents in thehorse. Simple, short (less than 6 inches) overthe needle catheters are perfectly adequate and areplaced as described in Chapter 9. Once it is certainthat a catheter is in the vein to its maximum lengthit should be secured in position with a partial skinthickness stitch and a stopcock or injection capattached (Fig. 11.16). The catheter may be keptpatent for many hours if its lumen is periodicallyflushed with heparin saline solution (10 IU/ml).Ideally the skin suture should be laid beforevenipuncture is attempted so that it may be tiedsecurely around the catheter without risk of displacingthis from the vein, but otherwise, thecatheter may be fixed in place with a drop of acrylateglue which will hold it whilst the suture is completed.There is no advantage to be gained from introducinga needle or catheter into the vein in adownwards direction away from the head except,possibly, for the infusion of large volumes of solutionssuch as guaiphenesin. Technical errors aremuch more likely to arise if attempts are made toperform venipuncture in this manner. The operationis more awkward: it is more difficult to assess

THE HORSE 279AFIG.11.16 Introduction of a catheter into the jugular vein.In (A) a catheter of the ‘over-the-needle’ variety is beingintroduced through an insensitive skin weal produced by the intradermal injection of 1ml of 2% lignocaine.It is usuallynecessary to make a small skin incision in the centre of the weal to prevent ‘belling-out’ of the catheter tip,or the catheterbeing pushed back along its introducing needle as the skin is penetrated. After penetration of the skin the vein is distendedby digital pressure and the catheter advanced well into the vein.In (B) the catheter and its occluding tap are being fixed inposition with partial skin thickness sutures.(It is helpful if these sutures are in position before the catheter is introducedbut this was avoided here for sake of clarity.)Bthe depth to which the needle is being inserted, itis more difficult to detect intracarotid injection andif the animal moves its neck the direction of movementwill be against the point of the needle thustending to transfix the vein. Care must be taken toavoid air embolism when a needle or catheter is

280 ANAESTHESIA OF THE SPECIESdirected downwards since its tip will be at a lowerpressure than its hub, predisposing to the aspirationof air if the hub is not closed off whenever aninjection is not being made. Very little air needs tobe aspirated to cause the horse to collapse – theauthors have seen one case where aspiration washeard to occur for less than one second through a23 G catheter.Where a catheter is to remain in place for sometime postoperatively, usually to enable the infusionof fluids, then long catheters are used. Thesecatheters are usually placed over guide wires bythe Seldinger technique and are always directedtowards the heart. Long catheters are not ideal fori.v. induction of anaesthesia (other than by infusiontechniques) nor for the very rapid administrationof fluids as their length increases resistanceand therefore slows the speed of injection. Whencatheters are left in place, there is a danger ofinfection and subsequent thrombophlebitis so fullsterile precautions are required for their placement,and in subsequent handling of the injectionports.PREMEDICATIONThe choice and dose of any premedicant drug willdepend on the physical condition and temperamentof the horse, the likely duration of the proposedexamination or operation and the nature ofthe anaesthetic technique to be employed. In manyrespects, the relative importance given to the premedicantdrugs or the anaesthetic agents is a matterof personal preference. Some anaesthetistsfavour heavy sedative premedication whichdecreases the quantities of sedatives and anaestheticsadministered later, while others habituallyuse light premedication and more of the anaesthetic.In the hands of their exponents both regimensappear to produce similar results.AnticholinergicsIn current practice anticholinergic drugs are notused in the routine premedication of horses,although they may be administered if requiredonce the horse is anaesthetized, for example if thesurgery is likely to provoke vagal reflexes orshould bradycardia develop. Doses of 0.01–0.02mg/kg i.v. atropine appear to be safe to use whererequired but nevertheless in horses, glycopyrrolate(0.005–0.010 mg/kg) is probably preferable(Singh et al., 1997), for it is shorter acting and doesnot readily cross the blood-brain barrier, thusbeing less likely to cause central excitatory effects.SedativesPremedication with sedative agents whilst thehorse is still in its accustomed accommodationgreatly improves the process of anaesthetic inductionas it keeps the horse calm, reduces apprehensionand fear, and makes procedures such as theplacement of catheters more pleasant for bothhorse and anaesthetist.AcepromazineIn many cases acepromazine (0.03–0.05 mg/kgi.m. or 0.03 mg/kg i.v.) given 30–60 minutes priorto anaesthesia is ideal for premedication; it calmsthe horse without making it ataxic and its longlastingeffects usually last throughout the wholeperioperative period, so contributing to a calmrecovery. Acepromazine reduces the dose of theparental anaesthetics used and reduces MAC ofvolatile anaesthetic agents (Heard et al., 1986). Theinfluence of acepromazine premedication on theamount of volatile anaesthetic agent requiredbecomes obvious when the effects of concurrentlyadministered short acting α 2 adrenoceptor agonistswane (usually 60–90 minutes); without acepromazinethe depth of anaesthesia lightens verysuddenly, necessitating a rapid increase in theinspired levels of volatile anaesthetic agents.The use of acepromazine for premedicationsignificantly reduces the overall anaesthetic risk(Johnston et al., 1995).α 2 adrenoceptor agonistsXylazine, detomidine and romifidine are widelyused as part of the anaesthetic induction processand they reduce markedly the dose of both i.v. andinhalation anaesthetic agents. However, they mayalso be used as classic ‘premedicants’ in whichcase their residual action must be taken intoaccount when deciding on doses to be used at

THE HORSE 281anaesthetic induction. Doses used i.v. for premedicationare approximately half those used for sedation(i.e. xylazine at 0.5 mg/kg, detomidine at 10µg/kg and romifidine at 50 µg/kg) so that thehorse is able to walk to the anaesthetic inductionarea. The i.m. use of α 2 adrenoceptor agonists hasbeen much neglected, but i.m. doses of 1 mg/kgxylazine or 20 µg/kg detomidine give excellentsedation after approximately 20 minutes. If thehorse is exceptionally difficult to handle, 40–50µg/kg detomidine (chosen because of the low volumeinvoved) may be given i.m., the horse left quietlyfor at least 20 minutes, after which time, in theauthors’ experience, i.v. injection has alwaysbecome possible, although occasionally only withthe aid of a twitch. In such horses i.m. injectionmay be given at any convenient site (the horseoften does not anticipate an injection in the pectoralmuscles) as swelling rarely occurs after theuse of i.m. detomidine.AnalgesicsOpioid analgesics may be used both to providepreoperative pain relief if necessary, when fullanalgesic doses are required, and to improve thelevel of sedation, when doses are usually reducedto half. Full doses may be required for difficulthorses, and in these circumstances can usuallymixed in the same syringe as the α 2 adrenoceptoragonist. In general mixing such combinations isnot recommended by the manufacturers as thenecessary tests to ensure chemical stability havenot been performed, but with difficult horses theremay only be one opportunity to carry out theinjection. If not already given, NSAIDs may beadministered so that they will be effective by thepostoperative period.INDUCTION OF ANAESTHESIAThe past 40 years have seen great improvements inequine anaesthesia but a routine method suitablefor every situation has yet to be discovered. Theanaesthetist must choose a suitable method withregard to the size, health and temperament of theindividual horse, the cost of the procedure and thefacilities and staff available.Facilities for inductionWith the exception of occasional emergency situations,anaesthesia should never be induced in horsewithout there being available the necessary apparatusto resuscitate the horse should it become necessary.Such apparatus includes endotrachealtubes, methods to administer O 2 and apply IPPV,and the drugs likely to be needed should cardiacarrest occur. In the hospital setting the apparatusneeded to administer volatile anaesthetic agents(anaesthetic machine and absorber circuit) will fulfilthis role. For field anaesthesia, a portable sourceof O 2 will be required. IPPV of the lungs can be satisfactorilyprovided by the use of a stream of oxygendirected into the trachea for the Venturi effectby a Hudson valve, or using an easily portable toand-frocircuit.The cardiopulmonary system of the anaesthetizedhorse must be monitored continuouslythroughout anaesthesia but the degree of sophisticationwith which this will be done will dependon the facilities available, and in the field may belimited to those of continuous observation, palpationof the pulse, and possibly the use of a batteryoperated pulse oximeter. The pulse oximeter is ofvariable use in the horse as many such instrumentscannot function with pulse rates below 40beats/minute. The favoured site for the probe isacross the nasal septum, as it is without hair, usuallywithout pigment, and sufficiently thin. Inequine hospitals monitoring is more sophisticatedand may include the electrocardiogram, ABP,peripheral pulse monitor, end-tidal gases and arterialand venous blood gases.Methods of control at anaestheticinductionFree fallIn this simplest method of control, one personholds the horse’s head as it becomes recumbent. Ifthe horse leans back as anaesthesia takes hold, thehandler holds the head down, which steadies thefall and prevents the horse going over backwards(Fig 11.17). With the type of induction whichoccurs following use of the dissociative agents thisis less necessary, and the handler simply has tosteady the head. If induction is in a padded box,

282 ANAESTHESIA OF THE SPECIESRing inpadded wallSwinginggateAppliedpressureBreastrestrainingropeHalter ropeFIG.11.17 Control of a horse during induction ofanaesthesia using the ‘free-fall’ method.the horse may be placed with its rump to a wall sothat the wall takes the weight; this makes inductionvery smooth, but occasionally results in a hindleg becoming trapped beneath the horse.The free fall method requires the minimum ofstaff and is the only practicable method in the field.Gate methodIn this method the horse is positioned against awall of the induction box, and restrained there by agate. A rope, which can easily be released, holdsthe gate in place and prevents the horse movingforward (Fig. 11.18). Usually when available severalpeople also press against the gate to support it.As anaesthesia is induced, the rope is released andthe gate opened so that the horse may sink to theground.A variation of this method manages without thegate, the horse being held against the wall by anumber of people. The horse is restrained and itsweight supported as it becomes recumbent byhead and tail ropes attached to rings in the wall ofthe induction box.Tilting tableIn this method the operating table top is tilted tothe vertical position; the adequately premedicatedor quiet animal is restrained against the table topFIG.11.18 Control of a horse during induction ofanaesthesia using the ‘gate’ or ‘swinging-door’ method.Induction to recumbency is aided by two or three peopleapplying pressure to the gate as the horse sinks towardsthe floor. An assistant restrains the horse’s head andprevents the horse from falling forwards or backwards.The breast control rope which prevents the horse fromwalking forwards is slackened off as the horse becomesrecumbent.by straps (Fig 11.19). As the horse loses consciousnessduring the induction process it is broughtsmoothly into lateral recumbency by restoring thetable top to its normal horizontal position. Themethod usually works very well but it is onlypossible where an adequate number of trainedpersonnel are available, and trouble occurs ifthe horse panics or a fault develops in thetable mechanism at a critical stage of induction.Once the horse is unconscious, padding must beplaced underneath it, so the method does notremove the necessity to lift the horse. The horsemay be allowed to recover on the horizontal tabletop and placed on its feet as soon as it is judgedable to stand by rotating the top to vertical; or thehorse may be transferred to a padded recoverybox.

THE HORSE 283agents such as ketamine. Either method may beassisted by the use of centrally acting muscle relaxantssuch as guiaphenesin or the benzodiazepineagents. The following section and Table 11.4 discusssome combinations which the authors havefound satisfactory. If the horse is not healthy modificationsmay have to be made to these protocols.For example, there may be times when the sideeffects of the α 2 adrenoceptor agonists are contraindicated,and conditions such as toxaemia orhypoproteinaemia reduce the quantity of anaestheticagent required.Hypnotic/anaesthetic agentsFIG.11.19 Induction of anaesthesia using a tilting tabletop.The sedated horse is restrained against the tablewhich is rotated to the horizontal position as the animalbecomes unconscious and relaxed.Usually induction ofanaesthesia is with guaiphenesin/thiopental orguaiphenesin/ketamine and 4 to 6 trained personnel areinvolved in manipulation of the table and animal.Intravenous regimes for anaestheticinductionIn normal clinical practice anaesthesia in adulthorses is induced with i.v. agents. The dose ofanaesthetic required in the healthy horse willdepend on the amount of sedative and opioidanalgesic it has received both as premedicationand just prior to anaesthetic administration. Thenumber of possible combinations of sedative andanaesthetic agents which are suitable for anaestheticinduction are enormous, and the choice willdepend on facilities, the state of the horse, and onpersonal preference. However, the majority ofinduction techniques are based on a combinationof sedative drugs either with hypnotic/anaestheticagents such as thiopental, or with dissociativeThe manner in which a horse becomes recumbentis similar following the injection of any of the hypnotic/anaestheticagents, and is typified by thatwith thiopental. Following injection of thiopentalthe horse tries to lean backwards and to lift itshead, which must be restrained to prevent thehorse losing its balance and possibly ‘going overbackwards’ (Fig. 11.17). With restraint, the horsesinks gently to the ground. Premedication with theα 2 adrenoceptor agonists slows the circulation in adose-dependent manner and the onset of unconsciousnessis delayed for 40–120 seconds aftercompletion of the thiopental injection. The horsemay make paddling or galloping movementswhen it first becomes recumbent; these movementsdisappear within 10–20 seconds as unconsciousnessdeepens.ThiopentalThiopental is a hypnotic/anaesthetic agent commonlyemployed. The dose required to induceanaesthesia in the horse depends on the amount ofsedation present (Table 11.4). As recovery from aninduction dose of thiopental depends on redistributionrather than elimination, reduction in the doseleads to a faster and better quality recovery.Thiopental at 15 mg/kg i.v. can be given rapidly tounsedated colts for castration; induction is adequatebut recovery, although rapid, may be veryviolent and this method cannot be recommended.Following premedication with acepromazine(0.03–0.05 mg/kg) given at least 30 minutes priorto anaesthesia, thiopental, at a dose of 10 mg/kg

284 ANAESTHESIA OF THE SPECIESTABLE 11.4 Some regimes suitable for the induction of anaesthesia prior to maintenance with volatileagents,or by TIVA. Anaesthesia results from a combination of the effects of the sedative premedicantdrugs and of the induction agents.Many combinations other than those listed here can be used safelyPremedication Anaesthetic Maintenance by further i.v.agents (TIVA)for short duration (20–30 mins) onlyAcepromazine,Thiopental,11 mg/kg i.v.or0.03–0.05 mg/kg i.m.or i.v. Methohexital,5 mg/kg i.v.Xylazine,0.5 mg/kg i.v.or Thiopental,7–8 mg/kg i.v. Thiopental,1 mg/kg i.v.(recovery may beDetomidine,0.01 mg/kg i.v.prolonged and of poor quality if totalthiopentone dose exceeds 12 mg/kg)Xylazine,1 mg/kg i.v.or Thiopental,5.5 mg/kg i.v.or Thiopental,1 mg/kg i.v.(maximal dose as above)Detomidine,0.01 mg/kg i.v. Methohexital,3 mg/kg i.v.Xylazine,1 mg/kg i.v. Ketamine,2.0–2.2 mg/kg i.v. Thiopental,1 mg/kg i.v.(maximal dose as above)(Diazepam,0.01–0.03 mg/kg i.v.given or increments of 0.5 mg/kg xylazine and 1 mg/kgimmediately following the ketamine ketamine i.v.as requiredwill improve relaxation,but maycause apnoea)Detomidine,0.015–0.02 Ketamine,2.0–2.2 mg/kg i.v. Thiopental,1 mg/kg i.v.(maximal dose as above)mg/kg i.v. (optional: diazepam,0.01–0.03 or increments of 1 mg/kg ketamine i.v.as requiredkg/i.v.as above)Romifidine 0.08–0.12 mg/kg i.v.Ketamine,2.0–2.2 mg/kg i.v.(optional: Thiopental,1 mg/kg i.v.(maximal dose as above)diazepam,0.01–0.03 mg/kg i.v. or increments of 0.02–0.04mg/kg romifidine andas above)1 mg/kg ketamine i.v.as requiredXylazine,0.5–1.0 mg/kg i.v. Tiletamine,0.05–1.0 mg/kg i.v.andDetomidine,0.01–0.02 Zolazepam,0.5–1 mg/kg i.v.mg/kg i.v.(Tiletamine and zolazepam aresupplied as a fixed 50:50 ratiocombination)Acepromazine,0.03–0.05 Guaiphenesin infused i.v. Thiopental,1 mg/kg i.v.(maximal dose asmg/kg i.m.or i.v. (approximately 25–50 mg/kg) above).Extra guiaphenesin may be infused,butuntil ataxia,then thiopental, maximal doses should not exceed 50 mg/kg,or5 mg/kg i.v. recovery may be delayedXylazine,0.5–1.0 mg/kg i.v.or Guaiphenesin infused i.v. Thiopental,1 mg/kg i.v.(maximal dose as above).Detomidine,0.01 mg/kg i.v. (approximately 25–50 mg/kg) until Extra guiaphenesin may be infused,but maximalor Romifidine,0.08 mg/kg i.v. ataxia,then thiopental doses should not exceed 50 mg/kg,or recovery5 mg/kg i.v.(Alternatively may be delayedthiopentone can be mixed withthe guaiphenesin,and the mixtureinfused until the horse becomesrecumbent)Xylazine,1 mg/kg i.v.or Guaiphenesin infused i.v. Thiopental,1 mg/kg i.v.or ketamine,1 mg/kg i.v.Detomidine,0.01–0.02 (approximately 15–30 mg/kg)mg/kg i.v.Romifidine,0.08 until ataxia,then ketamine,mg/kg i.v.1.5–2.0 mg/kg mg/kg i.v.Additional premedication with acepromazine (

THE HORSE 285its feet in approximately 30–40 minutes, andalthough there may be some ataxia, recovery isusually calm. The dose of thiopental is critical,under dosage through underestimation of weightmay lead to excitement during induction, and forthis reason it used to be common practice to followthe injection of thiopental with a small dose (0.1mg/kg) of succinyl choline, but this agent is nowused rarely.The use of i.v. α 2 adrenoceptor agonists (xylazine,detomidine or romifidine) just prior to anaestheticinduction reduces the dose of thiopentalrequired in a dose dependent manner, and alsoincreases the therapeutic index of the drug, meaningthat it is rare for underdosage to cause excitement.Xylazine 1 mg/kg or detomidine 20 µg/kggiven i.v. 5 minutes prior to induction reduces thenecessary dose of thiopental to about 5.5 mg/kg.Following doses of xylazine of 0.5 mg/kg or detomidineat 10 µ g/kg i.v. the dose of thiopentalrequired is about 8 mg/kg. Anaesthesia lasts for15–20 minutes (sufficient to enable castration) andif no further drugs are administered, the horse willregain its feet after 30–40 minutes. As yet there islittle published information available as to thecombination doses of romifidine and thiopental.Premedication with acepromazine prior to givingxylazine or detomidine does not appear to reducethe dose of thiopental subsequently requiredfor anaesthetic induction. Recovery to standing (inthe absence of maintenance agents) occurs in30–40 minutes, and with less ataxia than whenhigher does of thiopental are employed.Thiopental/guaiphenesinAfter premedication with acepromazine, and/orα 2 adrenoceptor agonists, guaiphenesin (at concentrationsof 5–15% depending on the personalpreferences of the anaesthetist and the preparationsavailable) is infused into the jugular veinuntil the horse shows marked ataxia (after approximately35–50 mg/kg). A bolus i.v. dose of about5mg/kg of thiopental then produces recumbencyand apparent unconsciousness. Panic due to muscleweakness may be seen if guaiphenesin isinfused without prior administration of sufficientsedative. It is also possible to combine guaiphenesinand thiopental solutions for infusion into thejugular vein to produce recumbency but there ismuch less control over anaesthesia when this isdone and profound respiratory depression can beproduced. Recovery from these agents aloneoccurs in 30–40 minutes, but there may be someresidual muscle weakness if high doses ofguiaphenesin are used. Where anaesthesia subsequentlyis maintained with other agents theeffects of guiaphenesin have time to wane.MethohexitalThe dose of methohexital required to induceanaesthesia appears to be half that for thiopental.For example 5 minutes after i.v. xylazine (1 mg/kg)or detomidine (15 µg/kg) anaesthesia can beinduced with 2.8 mg/kg of methohexital given i.v.as a bolus dose. Lateral recumbency occurs in asimilar fashion and time scale to that followingthiopental. However, following the use of methohexital,the breathing rhythm is often abnormal,three deep breaths being succeeded by 30–40 secondswithout any sign of respiratory activity.Similar breathing patterns occur in horses withother anaesthetic agents but the clinical impressionis that they are more common during anaesthesiainvolving methohexital. Anaesthesia lastsfor about 5 minutes and the horse usually standsup about 25 minutes later. Recovery is usuallyquiet and uneventful.PropofolA rapid injection of propofol (2 mg/kg i.v.)appears adequate for induction of anaesthesiawhen given 5 minutes after i.v. α 2 adrenoceptoragonists such as xylazine 0.5 mg/kg, detomidine15–20 µg/kg, or medetomidine 7 µg/kg (Nolan &Hall, 1985; Aguiar et al., 1993; Bettschart-Wolfensbergeret al., 1999a). At these doses of propofolanaesthesia appears to last for approximately 10minutes, with recovery to standing within 30 minutes.In all studies the animals became hypoxaemicand appeared very lightly anaesthetized,but where surgery was being performed (Aguiaret al., 1993), there was no response to surgical stimulation.Without premedication a dose of 4 mg/kgpropofol is necessary to induce anaesthesia andeven then horses show some excitement and

286 ANAESTHESIA OF THE SPECIESpaddling (Mama et al., 1995). With the currentpreparations of propofol available, it is difficult toinject even 2 mg/kg propofol sufficiently rapidly,and in large horses slow injection results in a poorquality of anaesthetic induction (Bettschart-Wolfensberger, 1999a). However, it is possible thatnew more concentrated preparations of propofolwill become available and these may make inductionof anaesthesia with this agent more practicableand perhaps, less expensive.Etomidate and metomidateEtomidate has apparently not been used in horses,and it is probable that current preparations wouldresult in the volume required being too large to bepracticable. However, the similar but no longeravailable compound, metomidate (2.25 mg/kg i.v.)following premedication with detomidine(10µg/kg) produced excellent induction prior tomaintenance of anaesthesia with halothane sincesignificant apnoea did not occur.Dissociative agentsWhen the dissociative agents, ketamine or tiletamineare given on their own to horses, they causestimulation rather than depression of the centralnervous system, with a form of excitement inwhich there is poor muscle relaxation, tremors andeven convulsions. Many drugs have been used inattempts to suppress these most undesirableeffects but only the α 2 adrenoceptor agonists andthe benzodiazepines have proved to be of any realvalue.The dissociative anaesthetic agents are noteffective in a single brain circulation time, andtherefore where sedation with an α 2 adrenoceptoragonist has preceded the i.v. injection of ketaminea large horse may take as long as 3 minutes tobecome recumbent. The method of achievingrecumbency differs from that seen followingthiopental; it is a much more gradual process, theanimal often taking a step or two sideways orbackwards before sitting back on its haunches andsinking to sternal recumbency. It then rolls gentlyover on to its side and may make one or two quitevigorous limb movements before becoming still.Once laterally recumbent, the animal settles muchmore quickly and the onset of unconsciousness ismore rapid when no attempt is made forcibly torestrain the head – if this is done the horse mayeven try to rise and can be very difficult to restrain.KetamineKetamine, following premdication with an α 2adrenoceptor agonist produces excellent inductionof anaesthesia followed by a spectacularly rapid,but usually very quiet, recovery. Xylazine1.0–1.1mg/kg, detomidine 20 µg/kg or romifidine80–100 µg/kg is given i.v. and then, once maximumsedation has developed (approximately 5 minutes),a bolus of ketamine (2.2 mg/kg) is injectedi.v. Lateral recumbency is assumed in 1–3 minutesafter the ketamine injection, the longer time occurringwith the larger animals. Anaesthesia continuesto deepen for 1–2 minutes after the horsebecomes recumbent, and even when eye movementscease, relaxation of the jaw muscles is notalways good and it may be necessary to prise themouth open for the passage of an endotrachealtube. Relaxation can be improved by the adminstrationof a benzodiazepine agent i.v. (usuallydiazepam 0.01–0.05 mg/kg) immediately after theketamine injection, although this tends to causefurther repiratory depression and should be usedwith caution in situations where facilities for IPPVare not readily available. If for any clinical reason itis desirable to give a lower dose of α 2 adrenoceptoragonist, then the dose rate of the benzodiazepinecan be increased to compensate. The classic signsand stages of anaesthesia are not recognizable;nystagmus and tear formation may be observedand the surest guide to the depth of anaesthesia isthe presence or absence of response to surgicalstimulation. When no other anaesthetic is given,depending on the degree of surgical stimulation,horses first raise their heads 10–30 minutes afterthe ketamine injection, roll into sternal recumbencysome minutes later and stand 5 or 6 minutesafter this. Termination of surgical anaesthesia isvery abrupt but recovery is remarkably free fromexcitement and horses usually stand at the firstattempt. Once standing there is very little evidenceof ataxia.The method is not without disadvantages. Thevery abrupt end of surgical anaesthesia when no

THE HORSE 287other agents are given can lead to difficulties, andindeed this rapid ‘awakening’ may become evidenteven when anaesthesia is continued withvolatile anaesthetic agents. Horses require verydifferent handling from that used when anaesthesiais induced with the barbiturates, and this is amatter of familiarity with the regime. However,the method appears to be a very safe way ofproducing short periods of anaesthesia. Cardiovascularparameters are well maintained (Muiret al., 1977; Hall & Taylor, 1981; Clarke et al., 1986),respiration is adequate and continuation of anaesthesiawith an inhalation agent or by total i.v.methods presents no problems.Ketamine may also be used with other premedicantagents or in other combinations. Acepromazinepremedication is inadequate prior to ketamineinduction. Many dose schedules utilizing guaiphenesintogether with α 2 adrenceptor agonistsand ketamine have been recommended. For example,xylazine (2.2 mg/kg) is given by i.m. injection20 minutes before 55 mg/kg of guaiphenesin isinfused as a 5% solution in 5% dextrose into thejugular vein. This is followed by the i.v. injection of1.7 mg/kg of ketamine (Muir et al., 1978b).Ketamine can be given with benzodiazepineagents alone (i.e. with no α 2 adrenoceptor agonists).In foals diazepam or midazolam (0.10–0.25 mg/kgi.v.) followed by ketamine (2.2 mg/kg i.v.) gives avery satisfactory anaesthetic; usually foals liedown following the benzodiazepine drug.However, in adult horses the combination is moredifficult to employ. Neither agent should be givenalone. As both have a variable onset of action,when administered together the quality of inductionis very variable depending on which agenttakes effect first (Clarke et al., 1997). One studyutilizing midazolam/ketamine found that evenafter three hours of subsequent halothane anaesthesia,recovery was complicated by muscleweakness, and in some cases it was necessary toantagonize the residual midazolam. The poorquality of induction and recovery with these benzodizepine/ketaminecombinations is unfortunateas during subsequent maintenance with volatileagents, heart rate, MAP and CO are maintained ata considerably higher value than when α 2 adrenoceptoragonists are used in the induction protocol(Luna et al., 1997).TiIetamine/zoIazepamThe idea behind the combination of tiletaminewith zolazepam is that there is already a benzodiazepinepresent to ensure muscle relaxation duringsubsequent anaesthesia. In the horse, however,this combination has always been used followingthe administration of an α 2 adrenoceptor agonist.This combination is used after xylazine (Hubbell etal., 1989) or detomidine premedication (Muir et al.,1999). Although it produces reasonably safe ‘shorttermanaesthesia’ of a little longer duration thanthat seen after xylazine/ketamine/diazepam, itoffers very little other advantage.Other i.v. techniquesEtorphineEtorphine is used in horses as ‘Large AnimalImmobilon’, a yellow solution containing 2.45 mgetorphine hydrochloride with 10 mg acepromazinemaleate per millilitre. The minimum dosefor horses is 0.5 ml of the solution i.v. per 50 kgbody weight. The i.m. route should only be used indire emergencies since it results in a period ofmarked excitement before sedation and anaesthesiaensue. Animals made recumbent withImmobilon are very stiff, with muscle tremors,severe respiratory depression, cyanosis, tachycardiaand hypertension. In male animals priapism isnot uncommon. Transfer to inhalation anaesthesiais usually not required because the effects ofImmobilon last about 45 minutes. Because of themarked effects in the body, Immobilon is not recommendedfor use in horses with cardiac problemsor liver damage. Animals should not beslaughtered for consumption by humans or otheranimals until 28 days have elapsed.The actions of Immobilon may be antagonizedby the injection of Revivon, a blue solution containing3 mg/ml of diprenorphine hydrochloride.A quantity of Revivon equal to the total volume ofImmobilon injected should be given i.v. as soon aspossible after the required period of restraint iscomplete. Most (but not all) horses regain their feetwithin a few minutes of this injection. Injectionof Revivon antagonizes only the actions of etorphine,hence analgesia is lost but sedation due tothe acepromazine is unaffected. Undesirable

288 ANAESTHESIA OF THE SPECIEShyperexcitability may be associated with the injectionof the antagonist and enterohepatic cyclingmay occur, causing excitement and compulsivewalking 6–8 hours after remobilization. An extrahalf dose of Revivon given subcutaneously at thetime of initial reversal may reduce the incidence ofthis delayed excitement, but should it still occur, afurther half dose of Revivon must be given. Theproduct information states that horses mustbe kept stabled for at least 24 hours after theadministration of Immobilon. Donkeys appearparticularly susceptible to delayed excitementwith Immobilon, and the current product informationno longer gives any recommendations for thisspecies. Combinations of etorphine with otheragents such as xylazine and azaperone haveproved no more satisfactory in practice thanImmobilon, and the attempts of some clinicians toobtain greater muscle relaxation by combining α 2adrenoceptor agonists with Immobilon are unwisein view of the respiratory and circulatory disturbanceswhich result.The use of Immobilon is associated both with adegree of risk to the life of the anaesthetist and tothat of even healthy horses. Large AnimalImmobilon is an extremely potent neuroleptanalgesicwhich is highly toxic to man. In man it causesdizziness, nausea, pinpoint pupils, respiratorydepression, cyanosis, hypotension, loss of consciousnessand death. In the event of accidentalinjection, spillage on the skin or splashing into theeyes or mouth immediate treatment is essential.Any veterinarian contemplating the use ofImmobilon should be thoroughly familiar with thelatest treatment measures set out in the productinformation sheet and ensure that adequate suppliesof (in date) naloxone are to hand. If it is consideredfor any reason that the use of Immobilon isabsolutely essential, it is clearly most unwise to useit unless another qualified person is present.Anaesthetic induction with inhalationagentsAlthough induction of anaesthesia in adult horseswith volatile agents of anaesthesia is possible inexperimental circumstances, it is not practicablefor clinical use with the very limited exception ofchloroform by Cox’s mask. However, in foalsanaesthesia can be induced with any suitablevolatile anaesthetic agent.ChloroformChloroform has little place in routine equineanaesthesia. It causes dose related liver toxicitywhile sensitizing the heart to adrenaline inducedarrhythmias, and its safe use requires a great dealof skill. Anaesthetic chloroform is no longer availablein the UK, but analytical quality chloroform isat least, if not more, pure. Despite potential problems,its use may be justified on the grounds ofeconomy for procedures such as castration insmall unbroken colts whose monetary or sentimentalvalue is minimal. Administration of chloroformby Cox’s mask to induce anaesthesia hasbeen described in a great deal of detail in earliereditions of this bookVolatile agents in foalsAn inhalation induction technique in young foalsavoids the necessity of giving drugs that theirimmature hepatic detoxicating mechanisms maynot be able to cope with. The size and lack of fat inthe foal mean that induction with volatile agents iseasily achieved, with minimal excitement. Themare should be sedated, but if possible allowed toremain until the foal is unconscious as to separatethe two at this time will lead to great distress andhigh levels of circulating adrenaline in the foal,with an increased anaesthetic risk. To achieveinduction of anaesthesia the standing foal isgently restrained and the inhalation anaesthetic(halothane or isoflurane) volatilized in a stream ofO 2 or N 2 O/O 2 administered through a face-maskapplied lightly over both nostrils. The volatileagent should be introduced gradually, its concentrationbeing increased every three or four breathsup to a maximum of 4 × MAC until consciousnessis lost. As the foal loses consciousness the attendantsmust lower it gently to the ground, the maskremoved, and an endotracheal tube passedthrough the mouth in the usual manner. Currentlythere is no evidence as to the safety of using thenew volatile agents, sevoflurane or desflurane, toinduce anaesthesia in foal. It is anticipated thatthey will result in very fast effective anaesthetic

THE HORSE 289induction, but their rapid speed of uptake willmean that great care is needed to prevent overdosage.The maximum concentrations required inrelation to MAC will be very much lower thanthose recommended above for halothane andisoflurane.An alternative to using a face-mask is to pass anendotracheal tube into the trachea via one nostriland administer the anaesthetic through this. Thebest endotracheal tubes for this purpose are of siliconerubber and about 55 cm long. NeonatalThoroughbred foals can accommodate tubes of7–9mm internal diameter and in 6 week old foals11 mm tubes can be passed with ease. Passage ofthe tube is greatly facilitated by prior preparationof the ventral nasal mucosa with lignocaine ointmentor gel and lubrication of the tube with thesame preparation. The possible complications ofthis technique have been reviewed (Webb, 1984)but with care they are rare. Anaesthetic systemsdesigned for use in adult human subjects are adequatefor foals up to 2–3 months of age.The recent survey of anaesthetic deaths inhorses (Johnston et al., 1995) found that in foalsinduction of anaesthesia with a volatile agentresulted in a higher mortality rate than when i.v.induction methods were employed. Whether thisfinding represents a genuine increased risk, orwhether it results from the fact that in the sickestfoals anaesthesia was induced with volatile agentshas yet to be elucidated.MAINTENANCE OF ANAESTHESIAEndotracheal intubationIn horses the passage of a Magill-type endotrachealtube (for which in the UK there is a BritishStandards specification) presents no great problem.With the anaesthetized horse in lateral recumbencythe head is moderately extended on theneck, the mouth opened, a suitable gag or biteblock put in place and the tongue pulled forward.The tube, lubricated on its outside with a suitablelubricant (e.g. K-Y Jelly, Johnson and Johnson), isintroduced into the mouth with the concave side ofits curve directed towards the hard palate andadvanced, keeping to the midline, until its tip is inthe pharynx. It is then rotated so that the concavityFIG.11.20 Passage of an oral endotracheal tube in ahorse.of its curve is towards the tongue (Fig. 11.20) andat the next inspiration it is pushed rapidly on intothe trachea. The rotation of the tube when its tip isin the pharynx ensures that it does not becomeimpacted on the epiglottis.The commonest causes for failure of the tube toenter the trachea are that the alignment of the headand neck is incorrect, that the tube is not in themidline of the orotracheal axis, or that the tip of thetube is sited ventral to the epiglottis: should any ofthese occur the tube should be withdrawn to clearthe epiglottis, and redirected for a further attempt.The technique for introduction of straight tubesor those with only a shallow curvature differsslightly: the head needs to be more extended onthe neck and often it is easier to introduce the tubewith its concavity towards the tongue, then torotate the tube 360 ° once in the pharynx in order todisconnect the soft palate from the epiglottis.Once in the correct position the tube shouldadvance down the trachea with minimal resistance;force should not be used. Resistance to passing thetube suggests either the endotracheal tube is toolarge, or that oesophageal intubation has occurred.Intubation through the mouth permits the useof the largest tube which will comfortably fit thetrachea. A 16.0 mm diameter tube is suitable forponies up to about 150 kg body weight, while a25–30 mm tube is adequate for most thoroughbreds.Heavy hunters and warmbloods often takesurprisingly large tubes.Endotracheal tubes can be passed through theinferior nasal meatus but this limits the size of the

290 ANAESTHESIA OF THE SPECIEStube to that which can be accommodated by thenostril, and therefore increases resistance tobreathing. The introduction and removal of nasaltubes entails the risk of damaging the turbinatebones, although with the modern soft siliconetubes this risk is reduced. Despite the limitations,nasal intubation can be very useful in cases wherethe surgeons require unobstructed access to themouth. In young foals the nasal passages are relativelymuch larger than in adults and tubes of adequatesize can be introduced through the nostril.The cuffs of endotracheal tubes are often damagedby contact with the horse’s teeth even when areliable mouth-gag is used to keep the mouth openduring intubation and extubation. Cuffed tubesmade of red rubber for use in horses are veryexpensive, but punctured cuffs should not berepaired with patches not vulcanized on, as otherwisethese patches may become detached duringanaesthesia and lodge in one of the smaller air passageswith disastrous results. Plastic tubes havemet with only partial success; either the plastic isso hard that atraumatic intubation is difficult or,when they reach body temperature they soften somuch that they become obstructed when the headis flexed on the neck. Siliconized latex rubbercuffed tubes are more successful, can be recuffed,and, although the smaller versions for foals, sheepetc. may require an ‘introducer’ before they can beinserted, those designed for adult horses are sufficientlystiff to enable endotracheal intubation to beperformed easily. Static charges on the siliconeattracts dust, and it is important that after use andcleaning it is not placed where it will attract suchdirt during the induction process.As the horse has poor laryngeal tone, the cuff ofthe endotracheal tube must be adequately inflatedif the IPPV is to be carried out, and a good seal isexceptionally important in cases of colic to preventinhalation of regurgitated material. Cuffs shouldtherefore be checked for leaks by leaving theminflated for a period of time prior to useThe Cole-pattern tube (Fig. 11.21), which has noinflatable cuff, has been used in horses but thesetubes have to be of the exact size needed for anygiven animal and accurately placed in the larynx ifthey are to provide an atraumatic seal which is sufficientlygas-tight for IPPV to be carried out withoutgross leakage of anaesthetic gases. They mustFIG.11.21 Cole-pattern endotracheal tube for thehorse.be used with care in young animals having softlaryngeal cartilages for in them forcible dilatationwith these tubes can seriously damage the larynx.They have been reported in association with acutelaryngeal oedema in two adult horses althoughwhether they were in fact the cause was not established(Trim, 1984).PositioningPractically the aim in positioning is:1. to reduce to the minimum possible thepressure at all points in order to enable adequateblood perfusion to muscles and to decrease thechance of a compartmental syndrome occurring2. to ensure that major veins are not obstructed.If this happens then pressure in the area drainedby these veins will increase until it reaches arterialvalues, after which time there will be no furtherperfusion to the area3. to avoid putting anything under tension.Nerves are particularly easily damaged bystretching as well as by direct pressure4. to allow surgical access.The first three aims are often at odds with thefourth, necessitating compromise and sacrifice ofsurgical convenience for the benefit of the horse.It is now generally accepted that the bestmethod to reduce pressure on the horse’s body isto position it on a soft foam mattress sufficientlydeep to allow the horse to sink right in (thus reducingthe unit weight at any one point) without ‘bot-

THE HORSE 291AFIG.11.22 The Snell infla-table.This is a portable,pnuematically raised table comprising of five stackedchambers.The top chamber provides the working surfaceand should not be fully inflated so that the horse lies on asoft,compressible surface.The lower four provide supportand height adjustment.It is placed in its deflated conditionalongside the anaesthetized horse which is then rolled onto it.The table is then inflated to the desired workingheight using an electrically powered air pump.(Manufactured by Snell-Wessex Ltd,Fosters Farm,Boyshill,Holnest,Sherborne,Dorset DT9 5PJ,UK).toming’ on the hard undersurface. The type ofmatting used in gymnastics is ideal. However, thehorse has to be lifted on to such a mat. Alternativesare air or water mattresses which may be partiallyinflated under the horse (Fig. 11.22). It is veryimportant that air mattresses are not fully inflated– the horse must still be able to sink in or no reductionin pressure is achieved. This is one of the timeswhen compromise from the surgeon is necessaryas operating on a horse which is lying on a soggywater or air bed is not conducive to the performanceof any delicate surgery.The edges of tables or overinflated air or waterbeds can cause pressure points and result in nerveor muscle damage. Operating tables may havesuch ‘edges’ in association with sections whichslide out, and if so, suitable pads and mattingto cover these pressure points are essential (Fig.11.23).When horses are positioned in lateral recumbency,the under front leg should be pulled forward,and both upper legs should be supportedparallel to the body (Fig. 11.24). This supportreduces pressure on the triceps muscles, brachialvessels and nerves, and also prevents obstructionof the venous drainage of the upper limbs. Supinehorses may be supported by a V-shaped back support(Fig. 11.25) but where such supports are used,BFIG.11.23 An operating table with many sections whichmay slide out (A) thus assisting the surgeons to make agood approach to the operating site.However,the edgesof hard padding around these separate sections arepotential‘pressure points’ and extra padding (B) shouldbe provided between them and the horse.care must be taken to use some soft padding orthe pressure on the triceps muscle may be sufficientto induce myopathy. The legs may be supportedon a hoist or tied to pillars but extendingboth hind legs, and in particular locking the stiflejoints of dorsally recumbent horses, should beavoided unless absolutely essential to the surgery,as it may result in severe hindlimb lameness. Thislameness is thought to be due to femoral nervedamage, but there may also be a component ofgluteal myopathy. If bilateral, the horse will beunable to rise. The problem is unrelated to weight– the authors have seen it in miniature Shetland

292 ANAESTHESIA OF THE SPECIESABThe head is very liable to damage at pressurepoints and to avoid damage to the masseter muscle,facial nerve and eyes, care must be taken toensure that the face is not allowed to fall over theedge of the table top or to remain in contact withsharp edges of halters or head collars. Whether inlateral decubitus or supine the head must not beover-extended (this leads to laryngeal paralysis)nor rotated on the neck. If possible the head shouldbe slightly raised during anaesthesia to ensuregood venous drainage and to avoid intense vascularcongestion of the nasal passages leading togross upper respiratory obstruction after extubation.When the anaesthetized horse has to bemoved the head should be supported in a normalposition in relation to the neck.Under field conditions, the facilities may notbe available to position the horse as suggestedabove. However, a horse in lateral decubitus mayhave adduction of the upper limbs prevented bysupporting them on straw bales, and the undermostforeleg may be drawn as far forward as possibleto minimize pressure on the brachial vesselsand nerves.AGENTS FOR THE MAINTENANCE OFANAESTHESIAIntravenous agents: total i.v. anaesthesia(TIVA)FIG.11.24 A well positioned horse in lateral recumbency.It is placed on a deep soft foam bed,into which it sinks,thus reducing the weight at any one point.The upper limbsare supported so that venous drainage is not impaired,and the other forelimb drawn forward.When a table isnot used the limbs can be positioned with cushions A.InB the limbs are supported in slings. An extra foamcushion was used to keep the head slightly elevated.ponies, and it can occur after a comparativelyshort time.Total i.v. anaesthesia for short procedures in thefield (such as castration) has been used for manyyears, but in the past available agents had such along duration of action that their use was veryrestricted. Today, drugs which are rapidly metabolizedand eliminated are being introduced andTIVA can be used for more prolonged proceduresas the duration of recovery after some of the morerecently introduced agents and combinations is nolonger than after anaesthesia with volatile agents.Also, reassessment of some of the older agents hasshown that many of their disadvantages can beovercome by using them in combination withother or newer drugs.The use of TIVA does not reduce the need forapparatus or for experienced staff. Most i.v. anaesthetictechniques cause as much, if not more respiratorydepression, than do volatile anaesthetics, and

THE HORSE 293FIG.11.25 Back support for supine horse.In use the support is covered with 3 inches (7.5 cm) thick foam padding.Theweight of the horse is taken by the dorsal spine and the spines of the scapulae,thus avoiding pressure on the back muscles.indeed overdose commonly causes respiratoryarrest, so it is still essential to have a means of deliveringoxygen to the horse and of providing IPPV ifrequired. ABP is better maintained than withvolatile agents, but it is now realized that this doesnot necessarily mean that there is no cardiovasculardepression; CO still may be reduced and peripheralperfusion poor. Adequate cardiopulmonary monitoringis as necessary with i.v. as with volatile agents.The current limitations to techniques of TIVA arethose of duration and of expense. Many drugs orcombinations are long acting and cumulative, soextending length of action with more drug mayresult in a prolonged and poor quality recovery. Theideal agents for use by infusion (propofol and someof the α 2 adrenoceptor agonists) have pharmacokineticssuch that neither they nor their active metabolitesare cumulative whatever the duration ofadministration. In a compromise between expenseand the ideal agents, the techniques suitable forTIVA can be considered in three categories: thosesuitable for short procedures such as castration (upto 30minutes) and which result in a very rapid recovery;those suitable for more prolonged use (up to1.5–2.0 hours), and those which could be extendedindefinitely should the surgery demand. Proceduresmay last far longer than anticipated, and ifnecessary anaesthetists must be prepared to changetechnique (e.g. to introduce volatile agents, orchange to different drug combinations) if required.TIVA for short procedures (up to 30minutes)The techniques for i.v. induction anaesthesiadescribed above (p. 284, Table 11.4 ) provide adequateanaesthesia for procedures lasting 10–15minutes and (except for Immobilon) anaesthesiacan be ‘topped up’ with increments of i.v. drugs fora period of time before cumulation occurs. Themost commonly used combinations for short termanaesthesia are combinations of the α 2 adrenoceptorswith ketamine or with thiopental. Anaesthesiais then extended with incremental doses ofthiopental or ketamine.If no additional agents are given, recovery fromketamine-based methods occurs within 20–25 minutesand is usually very smooth and well controlled.However, recovery can be abrupt, andsometimes the horse may awaken during surgerywith little warning so it is essential that a rapidmeans to deepen anaesthesia is to hand. The durationof surgical anaesthesia can be increased by theuse of local anaesthesia; this technique is particu-

294 ANAESTHESIA OF THE SPECIESlarly suitable for castration. Choice of the α 2 adrenoceptoragonist (xylazine, detomidine or romifidine)utilized prior to ketamine does not influencethe quality and duration of anaesthesia, or thespeed and quality of recovery (Kerr et al., 1996).With thiopental-based methods, recovery isslower (30–40 minutes), there is some hindlimbweakness, and often more that one attempt to riseis required. Nevertheless, with appropriate premedicationrising is usually calm. Although thehorse may still move in response to surgery (localanaesthesia is a good option to prevent this) it iseasy to anticipate, and the abrupt awakenings seenwith ketamine do not occur.Agents used to extend the duration ofanaesthesiaThiopental sodiumSmall doses (0.5–1.0 mg/kg i.v.) may be given toextend anaesthesia which has been induced witheither thiopental or with ketamine. The majoradvantage of thiopental is that it acts in a circulationtime and is ideal to bring an awakeninganimal quickly back under control. However,overdose may cause apnoea and, as the drug iscumulative, speed and quality of recovery dependon the total dose. Thus, if initial anaesthetic inductionwas with ketamine, more increments may begiven than is possible following induction usingthiopental. A total dose of 10 mg/kg still results ina calm recovery in an acceptable time; higher totaldoses may be safe but will lengthen recovery.Ketamine hydrochlorideAnaesthesia induced with α 2 adrenoceptor agonists/ketaminemixtures may be prolonged withadditional ketamine, but there is a danger of undesirableexcitatory effects unless the α 2 adrenoceptorinduced sedation is still adequate. In clinicalpractice, incremental doses of half the originaldose of both xylazine and ketamine are given asrequired. There will be a delay before these agentswill be effective. The xylazine/ketamine combinationcan be extended to give medium term anaesthesiaby administration of half the initial doseof both xylazine and ketamine at approximately20 minute intervals (Short, 1981). The combination,using infusions of the two drugs, has been used toprovide approximately 90 minutes of anaesthesia(Mama et al., 1998). With detomidine/ketaminecombinations only a further dose of ketamine(1mg/kg) is required initially to extend the duration,although if ketamine increments are to begiven more than 30 minutes after anaesthetic induction,it is probably advisable also to administera small dose of detomidine (approximately 5µg/kg). With romifidine/ketamine combinationsthe product information sheet suggests that incrementaldoses of both ketamine and romifidine aregiven to extend anaesthesia.To date there are no scientific reports as to theuse of ketamine (1 mg/kg i.v.) to lengthen theduration of anaesthesia induced with α 2 adrenoceptoragonist/thiopental, although anecdotalreports suggest that the method is practicable.Methohexital sodiumMethohexital (0.5 mg/kg i.v.) can be given toextend anaesthesia in the situations where incrementsof thiopental would otherwise be used.However, it is very respiratory-depressant andrecovery is violent if the horse is not well sedated.TIVA for medium duration procedures(30–90 minutes)Anaesthesia which needs to be prolonged for morethan 30 minutes is usually achieved by combinationsof α 2 adrenoceptor agonists, ketamine, and acentrally acting muscle relaxant – guiaphenesin ora benzodiazepine. (Table 11.5). Ideally any drugused for infusion to provide long term anaesthesiashould have a short half life of elimination so thatthere is no cumulation. Not all these agents havethe ideal kinetics, hence their limitations for usebeyond 90 minutes (although some extension maybe possible at the expense of a more prolongedrecovery).Xylazine and detomidine have adequatelyrapid kinetics (the information for romifidine iscurrently not available), but residual guiaphenesinwill cause muscle weakness in recovery, so methodswhich reduce the dose of this component arepreferred. It benzodiazepines are used, then they

THE HORSE 295TABLE 11.5 Some regimens of total intravenous anaesthesia (TIVA) suitable for providing anaesthesiaof from 30–90 minutes duration. All agents are given i.v.unless otherwise stated.Many variations ofthese combinations can be used safelyPremedication Anaesthetic MaintenanceAcepromazine, Chloral hydrate (10%) infused Thiopental,1mg/kg (maximal total dose0.03–0.05 mg/kg i.m.or i.v. until ataxia (50–60 mg/kg),then 12 mg/kg) or methohexital,0.5 mg/kg.thiopental,5–6 mg/kg or If anaesthesia needs to be extended beyond 45methohexital,2.5–3.0 mg/kg minutes,more chloral hydrate may be requiredXylazine,1 mg/kg or Ketamine,2.0–2.2 mg/kg The ‘Triple Drip’,a combination of guiaphenesin,α 2Detomidine,0.02 mg/kgadrenoceptor agonist and ketamine infused to effect.orFor details of how to prepare suitable mixtures,seeRomifidine,0.08 mg/kgbelowXylazine,1 mg/kg Ketamine,2.0–2.2 mg/kg Climazolam (0.4 mg/kg/h) and ketamine (6 mg/kg/h)followed after induction byClimazolam 0.2 mg/kgare infused during surgery. 20 minutes after cessationof infusion,the climazolam is reversed with sarmazenil(0.04 mg/kg)Additional premedication with acepromazine (

296 ANAESTHESIA OF THE SPECIESavailable. Anaesthesia is induced with xylazineand ketamine, then climazolam is given at0.2mg/kg i.v. Anaesthesia is maintained with aninfusion of climazolam 0.4 mg/kg/hour and ketamine6 mg/kg/hour. Infusion ceases at the end ofsurgery, but the benzodiazepine is not antagonizedwith sarmazenil (0.04 mg/kg i.v.) for 20 minutesin order to give time for the ketamine effectsto have waned. The system gives good cardiovascularstability and respiration is adequate but O 2 isusually given. Recovery occurs rapidly followingreversal of the benzodiazepine agent (Bettschart-Wolfensberger et al, 1996).Chloral hydrate/barbiturateChloral hydrate lost favour due to its irritantnature if injected outside the vein and to the factthat if used alone recovery is very slow. However,in combination with the barbiturates it gives goodmoderate term anaesthesia and administrationthrough long i.v. catheters reduces the risk ofperivascular injection. A 10% solution is infuseduntil the horse becomes ataxic (after 40–60 mg/kghave been administered) when thiopental(5mg/kg) or methohexital (2.5 mg/kg) is injectedi.v. as a bolus. Surgical anaesthesia is maintainedby injection of increments of barbiturates (thiopental1 mg/kg or methohexital 0.5 mg/kg). If anaesthesiais to extend for more than 45 minutes, it mayprove necessary to give more chloral hydrate(approximately 10 mg/kg but to effect). The needfor this becomes obvious if small increments ofbarbiturate fail to suppress paddling movements.If no further chloral hydrate is given, the horse willstand some 50–60 minutes after anaesthetic inductionand recovery is usually calm. Whilst anaesthetized,respiration is well maintained, the pulseis strong and mucous membranes are a healthypink with a fast capillary refill time, all suggestingthat there is minimal cardiovascular depression.TIVA for long procedures (2hours andmore)Propofol combinationsThe only anaesthetic agent which is sufficientlynon-cumulative in the horse to be used for veryprolonged anaesthesia is propofol (Nolan et al.,1996). Propofol however has several drawbacks: itis a poor analgesic, it produces severe respiratoryand moderate cardiovascular depression, and itscarrier results in accumulation of triglycerides inblood. In the horse there are additional disadvantagesthat with existing preparations, large volumesare required and at such volumes it becomesvery expensive. There must also be some concernas to the dangers of triggering hyperlipaemia insusceptible individuals, although to date this complicationhas never occurred. Nevertheless, ifTIVA is ever to become practical for anaesthesia ofunlimited time in the horse, propofol is the agentmost likely to be involved.A number of studies have looked at methods toreduce the dose of propofol by providing analgesiaand further sedation (Nolan & Hall, 1985;Taylor, 1989; Nolan et al., 1996; Flaherty et al., 1997;Carroll et al., 1998; Mama et al., 1998; Bettschart-Wolfensberger, 1999a; Matthews et al., 1999). Mostcombinations utilize α 2 adrenoceptor agonists,with or without ketamine. In all studies theauthors commented on the fact the horse appearedvery lightly anaesthetized, yet did not respond tosurgery.Betschart-Wolfensberger (1999a) investigatedthe use of continuous propofol and medetomidineinfusions to provide 4 hours of anaesthesia inponies. Medetomidine was chosen for its kineticsand its marked analgesic properties. Anaesthesiawas induced either with medetomidine/propofolor medetomidine/ketamine and an infusion ofmedetomidine at 3.5 µg/kg/hour commenced.The minimum propofol infusion required toprevent response to a noxious stimulus rangedfrom 0.06–0.11 mg/kg/minute and cardiovascularparameters were well maintained although oxygensupplementation was requried to preventhypoxia. Following 4 hours anaesthesia recoveryoccurred in approximately 30 minutes, and was ofexcellent quality. Mama et al., (1998) investigatedthe use of xylazine infusions of 35 µg/kg togetherwith propofol at either 0.15 or 0.25 mg/kg/min forone hour; anaesthetic quality was excellent but atthe higher doses there was marked hypoxia andrecoveries were delayed. Flaherty et al., (1997)maintained anaesthesia in ponies with an infusionof ketamine (40 µg/kg/min) and propofol

THE HORSE 297(0.124mg/kg/min); anaesthesia was adequate forcastration and recovery was smooth.ANAESTHETIC MAINTENANCE WITHINHALATION AGENTSVolatile agentsHalothaneHalothane’s special advantages were (and still are)reasonably rapid induction and recovery, minimalexcitement during induction or recovery, adequatereflex suppression and sufficient muscle relaxationto allow most surgery to be performed, lack of toxicityand ease with which anaesthesia can be controlled.Halothane causes a dose-dependent fall inABP and CO and a rise in CVP. The fall in CO isdue to a direct depressant effect of the agent on themyocardium and falls of up to 55% of the nonanaesthetizedvalues have been recorded (Hall etal., 1968). There is a marked respiratory acidosis inspontaneously breathing halothane-anaesthetizedhorses and while this can be overcome by IPPVthis causes a further fall in CO (Steffey &Howland, 1978). Schatzmann (1982) showed thathypoxaemia causes a respiratory drive in horsesanaesthetized with halothane in air, thus demonstratingthat hypoxia can overcome halothaneinducedrespiratory depression.In horses it is remarkably difficult to judge thedepth of unconsciousness during anaesthesia withhalothane (or the other volatile agents) as hypoxiafrom any cause results in sympathetic stimulationand signs such as nystagmus, sweating, hyperventilationand even movement. These may be taken assigns of inadequate depth of unconsciousness bythe inexperienced anaesthetist, with disastrousconsequences. As the MAC value for halothane isabout 0.9% it is possible to monitor the depth ofhalothane by continuous measurement of the endtidalconcentration. The end-tidal values needed tomaintain anaesthesia depend on the sedative premedicationand anaesthetic induction techniqueemployed.Following induction of anaesthesia withthiopental, when O 2 alone is used as the carriergas, stable maintenance of anaesthesia is usuallyachieved with end-tidal concentrations of0.7–1.1% halothane; when induction is with ketamine,once the effect of the α 2 adrenoceptoragonist has waned end-tidal concentrations of1.1–1.3 % are frequently required. Halothane is apoor analgesic; horses which are apparently wellanaesthetized may respond suddenly to surgicalstimulation. Many of such responses are spinalreflexes, and are best prevented by provisionof analgesia. ABP and HR during halothaneanaesthesia also will depend on other agentsadministered. The decrease in ABP can give anindication of the depth of anaesthesia, but modernpractice of treating hypotension with positiveinotrope agents will counteract this fall andremove this sign.Horses normally regain their feet within about30 minutes following the termination of halothaneadministration after induction with xylazine/ketamine;after acepromazine premedication andthiopental induction, recovery takes about twiceas long. Shivering is often seen during recovery;the reason is unknown – it does not seem to berelated to body or environmental temperature andusually is of no importance. However, by increasingO 2 demands it may be harmful to horses sufferingfrom respiratory and/or cardiovasculardiseases which limit O 2 uptake when they arebreathing air. Quality of recovery depends on theinjectable drugs which have been administered, onthe surgery performed and the presence orabsence of pain. Recovery tends to be better followingthiopental induction compared to ketamineinductions (Young & Taylor, 1993), possiblybecause a prolonged recovery enables more of thehalothane to be eliminated before the horse tries tostand. Horses may take several attempts to rise,and show a measure of incoordination after recoveryfrom halothane, but usually remain calm.However, horses should not be made to walk (e.g.from recovery to loose box or stall) within 10–15minutes of standing up.IsofluraneIsoflurane has been used for anaesthesia in horsesfor approximately 15 years (Steffey et al., 1977; Steffey,1978; Steffey & Howland, 1980). In many waysit is very similar to halothane, and the signs of depthof anaesthesia in horses and the potential for a suddenresponse to surgery are identical with both

298 ANAESTHESIA OF THE SPECIESagents. However the kinetics and the cardiopulmonaryeffects of isoflurane and halothane differ.At equipotent doses isoflurane causes a smallerfall in CO than does halothane, and thus its effecton arterial hypotension mainly results from decreasedperipheral resistance (Steffey & Howland,1980). These differences between the cardiovasculareffects of halothane and isoflurane are stillapparent following anaesthetic induction with i.v.agents (Taylor, 1991; Lee et al., 1998c). However,isoflurane is more respiratory depressant than ishalothane (Steffey et al., 1980) and it is advisable toperform IPPV on isoflurane-anaesthetized horsesnot surgically stimulated in order to avoid hypoxiaand hypercapnia. The kinetics of isoflurane meanthat induction and changes in depth of anaesthesiaare rapid and recovery is impressively quick.However, the quality of recovery can be poor(Rose et al., 1989), especially where ketamine wasused for anaesthetic induction, and it is usual toadminister a further dose of an α 2 adrenoceptoragonist at the end of anaesthesia to delay recoveryand improve its quality.Opinions diverge as to the relative merits ofhalothane and isoflurane for prolonged anaesthesiain the horse. As yet there is no evidence thatisoflurane is safer than halothane; indeed in themulti-centre survey of equine deaths associatedwith anaesthesia (Johnston et al., 1995) horseswhich received isoflurane were more likely to diethan those receiving halothane but this may havebeen due to the selection of isoflurane for the morecritical cases.EnfluraneEnflurane may be used for equine anaesthesia(Steffey et al, 1977; 1978; Taylor & Hall, 1985), buthas not gained popularity for a number of reasons.The MAC value of enflurane is about 2% and, clinically,end-tidal concentrations of about 2.3% producesatisfactory surgical anaesthesia afteracepromazine premedication and thiobarbiturateinduction. However, with large animals it is difficultto achieve this end-tidal concentration usingthe commercially available vaporizers (maximumof 5% enflurane) unless economically unacceptablehigh flows of fresh gas are added to therebreathing systems. Respiratory depression withenflurane is marked, and if IPPV is used to overcomethis, then hypotension can be severe or evenfatal. Deep enflurane anaesthesia is associatedwith abnormal twitches in the muscles of the head,neck and forelimbs which become progressivelymore pronounced as the end-tidal concentration ofenflurane increases. Recovery from enfluraneanaesthesia is very rapid, but it is associated withoccasional bouts of excitement and more shiveringand incoordination than is recovery fromhalothane (Taylor & Hall, 1985).SevofluraneMAC of sevoflurane in the horse is 2.3% (Aidaet al., 1994) and despite the fact that most commercialvaporizers currently have a maximum outputof 5%, low solubility and rapid uptake means thatthere are no problems in achieving suitable endtidalvalues. Like other volatile anaesthetic agents,sevoflurane causes dose related depression of respiration,CO and ABP (Aida et al., 1996) but clinically,following anaesthetic induction withinjectable agents, the cardiopulmonary depressionis similar in extent to that caused by isoflurane(Grosenbaugh & Muir, 1998). The speed withwhich anaesthesia can be deepened means there israrely a need to give additional injectable anaestheticagents during anaesthesia. However, therapidity of uptake is such that care must be takennot to overdose in the early stages of anaesthesia.Recovery from anaesthesia is very fast, but itsquality is variable. Without further sedation theauthors have found it to be poor, but if xylazine isadministered to horses as soon as sevoflurane isterminated acceptable quality recovery occurs inabout 30 minutes, and is often better than followingisoflurane anaesthesia (Aida et al., 1997;Matthews et al., 1997).If sevoflurane is priced at an affordable level(currently it is very expensive) it may well replacecurrently employed agents.DesfluraneTrials of desflurane in the horse have been verylimited. However, the few studies which havebeen performed suggest that desflurane has majoradvantages for use in this species (Jones et al., 1995;

THE HORSE 299Clarke et al., 1996; 1996a; Tendillo et al., 1997). Thekinetics of desflurane are such that the end-tidalconcentration reaches inspired concentrations in amatter of minutes, even in a large horse, and recoveryis equally as fast. Consequently, control ofanaesthesia is very easy. The MAC of desflurane inthe horse is approximately 7.5%; following i.v.induction the horse is connected to the circle circuitwhich has been primed with 8% desflurane inO 2 . In the first 10minutes the circle system is emptiedtwice to reduce the contained N 2 concentration,but after this time the circuit can be run closed– the fresh gas flow rate still containing 8% desflurane,together with enough O 2 to replace that lostby utilization and by leaks from the circuit (usuallyabout 3 litres/minute in a large horse). The lowflow rates used throughout mean that desfluranebecomes comparatively inexpensive to use – in theUK it costs less than halothane. If anaesthesia istoo light, the bag is emptied and refilled with aconcentration 1% above the previous level, anddepth of anaesthesia changes within a veryshort space of time. Horses anaesthetized withdesflurane rarely react suddenly or violently tosurgical stimulation, but occasionally if anaesthesiais too light, they exhibit muscle tremor and it issometimes necessary to increase inspired desfluraneconcentration to as much as 10% to stopthis. Recovery from anaesthesia is also very fast –unsedated animals attempt to rise within 6–10minutes of withdrawal of desflurane, andalthough they remain calm, are still weak and mayfall forward. It is now routine to administer a smalldose of i.v. xylazine (0.1– 0.2mg/kg) at the end ofanaesthesia, after which horses get to their feet inabout 15–20 minutes in a calm and coordinatedmanner.The use of desflurane is not without its problems.Cardiopulmonary depression is dosedependentand is similar to that of equipotentdoses of isoflurane (Clarke et al., 1996a). At alveolarconcentrations sufficient for surgery CO is wellmaintained, although there is marked hypotension.The rapid kinetics and very fast change indepth of anaesthesia mean that is easy to overdose,and in early work, before it was realized that theinitial inspired concentration of desflurane neededto be very little higher than MAC, some horsesbecame very hypotensive (Jones et al., 1995).Desflurane is unpopular for use in man and it isquestionable as to how long it will be available.This is unfortunate, as the rapid and completenature of recovery from desflurane means that it isan excellent anaesthetic agent in horses.Nitrous oxideThe use of N 2 O is controversial. Its analgesic propertiesensures that less of the volatile agents whichlack analgesic properties are required (Steffey &Howland, 1978a). The disadvantage lies in thepotential for causing hypoxia. N 2 O will reducethe PiO 2 and particular care needs to be takenwhen it is used in a rebreathing system. N 2 Oalso passes into the gut spaces, increasing theirvolume and reducing FRC, thus resulting in agreater fall in PaO 2 than can be explained by thereduction in PiO 2 alone (Lee et al., 1998). The use ofN 2 O at the phase of transfer from i.v. induction tomaintenance speeds uptake of the volatile agentby the ‘second gas effect’. However, increasing thealveolar concentration of volatile agent by thismeans will result in a greater degree of cardiopulmonarydepression. N 2 O can provide useful analgesiabut in the horse it should be used only insituations where it is possible to monitor arterialblood gases.General points in relation to maintenanceof anaesthesia using volatile agentsMethods of administrationIn equine anaesthesia volatile anaesthetic agentsare administered via a circle or to-and-fro absorptionsystem using an out-of circuit vaporizer, andfor reasons of economy, they should be used withas low a flow of fresh gas as is practicable.However, the limitations to the use of minimumflows in the early phase of anaesthesia are (a) thenecessity to remove N 2 from the animal and thebreathing system, and (b) the need to maintainadequate inspired concentrations of volatile agentat a time when it is being taken up by the animal(Chapter 9). The simplest way to use a low-flowsystem is to restrict the method to the carriergas O 2 and only one volatile anaesthetic suchas halothane or isoflurane. At the outset the

300 ANAESTHESIA OF THE SPECIESanaesthetic system should be primed with O 2 andup to 4% of halothane or isoflurane (less in animalswith circulatory dysfunction). Following anaestheticinduction, the horse is connected to the systemwith fresh gas flow of 6–8 l/min (still carryingup to 4% of the anaesthetic agent). The excess ofgas is vented via the (scavenged) exhaust valve,thus reducing N 2 and keeping the inspired anaestheticagent concentration at an adequate level.The vaporizer setting is reduced in accordancewith the clinical needs of the animal. At the end of10–15 minutes, provided the reservoir bag is fillingwell the fresh gas flow can be reduced to about4 1/min. At these flows rates, with a large horsegiven halothane the inspired concentration will beapproximately half that of the vaporizer setting.The reason for this is simply that the mass ofhalothane delivered to the circuit at this low flowrate is insufficient in the first few hours of theanaesthetic period to make up the net losses fromthe breathing system to the animal’s tissues.Reducing the flow rate still further (the minimumneeded is that required to keep the reservoir bagfilled) will increase the difference betweeninspired concentrations and the vaporizer setting.If the depth of anaesthesia needs to be altered, thereservoir bag should be emptied and the new concentrationof agent given with a high flow of O 2until the required depth is achieved.The more insoluble the anaesthetic, the shorterthe time required for the tissues to become saturatedand therefore the closer is the inspired concentrationto the vaporizer setting. Isoflurane is givenin a similar manner to halothane, but since it is lesssoluble, the vaporizer setting and the flow ratescan be reduced more rapidly; with sevofluranethese changes occur even faster, and with desfluraneinspired settings are close to those of thevaporizer within minutes, even when very lowflow rates are used throughout.With all volatile anaesthetic agents difficulty canbe experienced in the transition to anaesthesia afterinduction by an i.v. technique. When the horse isfirst connected to the breathing system respiratoryarrest frequently occurs as a result of drug inducedrespiratory depression, removal of the hypoxicdrive through high PiO 2 (Steffey et al., 1992) and,possibly, the sudden imposition of expiratoryresistance. The problem can be overcome by IPPV,but careful monitoring is needed to ensure thatoverdose does not occur. Attempts to hasten theuptake by the administration of high inspired concentrationscan provoke cardiovascular collapse.Additional analgesiaIdeally, additional analgesia should be provided tohorses anaesthetized with halothane or isofluraneprior to the start of painful surgery. Local nerveblocks, where practicable, totally reduce response tosurgery and may also provide postoperative analgesia.NSAIDs are often given preoperatively orintraoperatively but there no evidence that their usereduces MAC. The place of opioids is controversial;many anaesthetists consider that butorphanol(0.02–0.04 mg/kg) or morphine (0.1–0.2 mg/kg)improve the quality of anaesthesia and preventmovement in response to surgery, but in some individualanimals even under anaesthesia their effectis to produce excitement and the dose of volatileanaesthetic needs to be increased to counteract this.Experimental studies have failed to demonstrate anaction of opioids on MAC in the horse (Matthews &Lindsay, 1990; Pascoe et al., 1993). Once the horsehas responded to surgery, a small dose of thiopental(0.05–0.10 mg/kg) will rapidly regain control,although it may cause a fall in ABP and transientapnoea. Incremental doses of ketamine (0.1–0.2mg/kg i.v.) may be given for additional analgesia,but the total dose should not exceed 2 mg/kg, andshould not be given in the last half hour of anaesthesia.Other options are α 2 adrenoceptor agonistsgiven as bolus injections (0.1 mg/kg xylazine or2µg/kg detomidine) or by infusion.TREATMENT OF CIRCULATORYDEPRESSIONIn the horse, hypotension is common duringanaesthesia with volatile agents, and as thisparameter is easy to measure, it has usually beenroutine practice to equate such hypotension withcardiovascular depression. However, it is nowrealised that, although it is essential that ABP isadequate to perfuse vital organs, once this ‘opening’pressure is reached then, as discussed aboveperfusion and peripheral blood flow depend onCO. Improving ABP by vasoconstriction may

THE HORSE 301result in a fall in CO, presumably as the result ofincreased afterload (Wagner et al., 1992; Lee et al.,1998a). The aim of cardiovascular support is,therefore, to increase ABP to an acceptable level(usually taken as a MAP of 65–70 mmHg) by theimprovement of CO and blood flow. A number ofmethods of providing such support have beenadvocated and investigated in horses anaesthetizedwith volatile agents. Often the findingsconcerning efficacy and dosage at different centresdo not agree, probably because of differingresponses in individual animals. In clinical practicemore than one of these methods of supportmay be needed. Few studies have examined suchtreatments in horses anaesthetized with i.v. agentsalthough it is now recognized that cardiovascularsupport still may be required if good peripheralperfusion is to be maintained.Increase in circulating fluid volumeAn increase in the circulating fluid volume tomatch the increased volume of the dilated vascularbed will restore the venous return. The simplestmethod entails the i.v. infusion of 5–20 litres of isotonicfluid (usually lactated Ringer), depending onthe size of the animal, as rapidly as possible immediatelyafter the induction of anaesthesia, althoughover-enthusiastic adminstration may causeperipheral oedema. The use of hypertonic saline (4ml/kg) in anaesthetized horses has been reviewedby Gasthuys (1994). When given prior to anaesthesiaand followed by a slower infusion of lactatedRinger it improves blood pressure during anaesthesia(Dyson & Pascoe, 1990). However, Gasthuyset al. (1994) found that when hypertonic saline wasgiven to halothane anaesthetized ponies, theimprovement in CO and ABP was significant onlyat a time point 5 minutes after the cessation of infusion.During the actual infusion of hypertonicsaline ABP fell, and these workers suggest thatthe method is not ideal where hypotension alreadyis severe. Gelatin-based compounds are not suitableas volume expanders in the normovolaemichorse (Taylor, 1998) as the volumes required aretoo great, but starch solutions have provedvery effective in clinical practice for improving thecirculation in endotoxic horses (Bettschart-Wolfensberger, personal communication, 1999).Positive inotropesMany of the sympathomimetic agents are easilyoxidized to inactive compounds on exposure to air,and thus should be prepared to the required dilutionjust prior to use. This property may explaindiffering results and differing recommendationsas to dosage and efficacy. Fortunately, in clinicalpractice some changes in potency are acceptable asthe drugs are administered to effect by infusion.The pharmacological action of dopamine, dobutamineand similar agents is to increase heart rate,yet if given too fast to anaesthetized horses bradycardiaor even heart block may occur. This appearsto be a vagally mediated reflex to the improvingABP, and if these drugs are given after treatmentwith an anticholinergic agent, tachycardia and arise in ABP occurs with very low doses of the sympathomimetic.Bradycardia can be avoid by commencingthe infusion of sympathomimetic slowly,then gradually increasing the dose as required.DopamineDopamine is a naturally occurring precursor ofnoradrenaline which exerts its action at α 1 , β 1 andβ 2 , and dopaminergic adrenoceptors. In horsesinfusions of 2.5–5.0 mg/kg/min improve COwhilst causing vasodilation. Renal perfusion isincreased (Trim et al., 1985; 1989) and both CO andABP improved in horses with endotoxic shock(Trim et al., 1991). Higher doses may cause vasoconstrictionvia α 1 activity. Signs of overdose aretachycardia and associated arrhythmias, and trembling(Lee et al., 1998a) but these effects cease assoon as the infusion rate is reduced.DobutamineDobutamine exerts its actions at both α and βadrenoceptors (β actions predominating at lowdoses), but is devoid of action at dopaminergicreceptors. In anaesthetized horses infusions of from0.5–5.0mg/kg have been found to improve both COand ABP (Swanson et al., 1985; Donaldson, 1988;Gasthuys et al., 1991a; Lee et al., 1998a). Overdose ofdobutamine causes tachycardia with associatedarrhythmias (which may be dangerous in the presenceof hypercapnia) but lack of dopinergic activitymeans that muscle tremors do not occur.

302 ANAESTHESIA OF THE SPECIESDopexamineDopexamine is a new synthetic catecholaminewhich has marked activity at β 2 receptors with alesser action at β 1 and dopaminergic sites. Itimproves CO through a positive inotropic effect,whist causing vasodilation, reducing afterload andimproving renal perfusion. Muir (1992; 1992a)demonstrated in conscious and anaesthetizedhorses that at doses of 1 µg/kg/min or more, COand HR increased, whilst systemic vascular resistancedecreased. In conscious horses ABP changeswere minimal but in anaesthetized animals dopexamineinfusion caused a dose-dependent increase.These advantageous cardiovascular effects in anaesthetizedhorses have been confirmed by otherworkers (Young et al., 1997; Lee et al., 1998), but inthese later studies under halothane anaesthesiadopexamine was found to cause unacceptable sideeffects. The initial response to infusion of the drugwas a fall in end-tidal anaesthetic agent (presumablybecause the vasodilation had opened underperfusedareas which then took up the halothane)and great difficulty was encountered in keepingthe animals unconscious. Higher doses causedsweating, tachycardia and tremor. When infusionwas stopped, ABP and heart rate continued to rise,and side effects did not abate for a considerableperiod of time. The quality of recovery was poorand in one study two horses developed postanaestheticcolic. The cardiovascular effects of dopexamineare ideal for circulatory support, and the sideeffects almost certainly result from overdosage, butconsiderably more experimental work is requiredto elucidate the correct dose before this agent canbe recommended for use in clinical practice.Phenylephrine and methoxaminePhenylephrine and methoxamine both act as α 2adrenoceptor agonists, and increase arterial bloodpressure by vasoconstriction. An infusion dose ofphenylephrine of 0.25–2.00 µg/kg/min in anaesthetizedhorses raises blood pressure but CO andmuscle blood flow fall or are unchanged (Lee et al.,1998). These vasoconstrictor agents should notroutinely be used to treat hypotension in anaesthetizedhorses but may have a role where all othermethods have failed.CalciumThe use of calcium to counteract anaestheticinduced cardiovascular depression has been advocatedfor many years but much of the evidence asto dose and efficacy is anecdotal, and the differingavailability of elemental calcium in preparations ofdifferent calcium salts sometimes makes comparisonsbetween studies difficult (Gasthuys et al.,1991b; Grubb et al., 1994). Calcium borogluconate,being readily available in veterinary practice, is acommon choice and up to 300 ml of a 40% w/vsolution may be given prior to or during anaesthesiaby slow i.v. infusion. Another recommendationis an infusion of 0.25–2.00 ml/kg/min of 10% calciumgluconate (Daunt, 1990). In clinical practicecalcium infusions tend either to be very effectiveor almost totally ineffective in improving ABP andperipheral blood flow. The rationale of the use ofcalcium is that plasma calcium levels fall duringanaesthesia with volatile agents. Whether calciumhas any effect in improving CO depressed by i.v.agents is not known.Anticholinergic agents:glycopyrrolate and atropineThe advantages and disadvantages of the use ofanticholinergic agents in equine anaesthesiahas been discussed above. However, during anaesthesiawith volatile anaesthetic agents bradycardiamay contribute to the fall in CO and this is particularlylikely to be the case if α 2 adrenoceptoragonists have been used in the anaesthetic protocol.Atropine (0.01 mg/kg) or glycopyrrolate(0.005 mg/kg ) given i.v. often do not increaseheart rate, but following their use, small doses ofdopamine or dobutamine do, with a spectaculareffect on CO.USE OF MUSCLE RELAXANTSCentrally acting muscle relaxantsGuaiphenesinWhere guiaphenesin has been used as part of theanaesthetic induction technique, it will improvemuscle relaxation for an hour or more. Doses ofguaiphenesin of 3 g and 5 g/ 50 kg may be given tothe anaesthetized horse and will produce some

THE HORSE 303relaxation without interfering with respiratoryactivity but when given in this way it causes amarked fall in ABP, probably through a negativeinotropic effect (Pascoe et al., 1985).BenzodiazepinesBenzodiazepines may also be administered intraoperativelyfor their muscle relaxant properties.However, when given to horses already anaesthetizedwith volatile anaesthetic agents, benzodiazepinescause marked respiratory depression.Neuromuscular blocking agentsFor many years neuromuscular blocking agentshave been used sparingly in equine anaesthesia(other than suxamethonium at induction of anaesthesia),the major fear being that residual muscleweakness when the horse tried to rise wouldadversely affect the quality of recovery. The adventof the short acting easily reversed competitiverelaxant atracurium changed this, and neuromuscularblocking agents are now widely used notonly to aid abdominal, ophthalmic and thoracicsurgery, but in general and orthopaedic surgery toprevent the sudden reflex responses which sometimesoccur.The rules for the use of neuromuscular blockingagents are, as for any species: (a) that the facilitieswhich enable immediate and sustained IPPV areavailable, and (b) that it is possible to be certainthat the horse will be unconscious throughout theduration of their effect.There is a wide variation among individuals inthe response to a given dose of neuromuscularblocking agent and in rate of recovery from blockade.Also, some antibiotic agents such as gentamycingreatly reduce the dose of relaxantrequired. For this reason no attempt should bemade to administer them in fixed doses; theyshould always be given so as to produce just thedesired effect. An incremental dosage regimenenables this to be done; about one-half the anticipatedfull dose is given initially and further incrementsof half this initial dose are given at 3–5 minintervals until the desired degree of relaxation isobtained. Only small doses are needed to suppressunwanted muscle movements during generalanaesthesia (e.g. in eye surgery) but large doseswill be required to produce the nearly completeblockade demanded by some surgical procedures.In every case the aim should be to use only a minimumdose and to ensure a complete recovery ofneuromuscular function before the termination ofanaesthesia. If unwanted muscle tone is returningtowards the end of a surgical procedure it isusually wiser to restore relaxation by a slight deepeningof anaesthesia rather than the administrationof more neuromuscular blocker.Clinical monitoring of neuromuscular block isfacilitated by the use of a peripheral nerve stimulator(Chapter 7) which may be used on the facial orsuperficial peroneal nerves and the strength ofcontraction of the relevant muscles estimated bymanual sensing at the muzzle or toe. If this facilityis not available, myoneural block may be monitoredby careful observation of the breathing andgeneral muscular activity of the anaesthetizedhorse. Signs of partial blockade include brief, weakinspiratory movements, without holding of inspiration,and feeble, unsustained withdrawalresponses to painful stimulation. One extremelysimple objective test is measurement of airwaypressure with a water manometer when the endotrachealtube is occluded before an inspiratoryeffort. No significant degree of myoneural block ispresent if the horse can generate a pressure in theoccluded airway of more than 25 cm H 2 O (2.5 kPa)below atmospheric pressure. If a degree of block ispresent during anaesthetic recovery the horse isunable to stiffen the neck or hold up the headwhen attempting to sit in sternal recumbency, or itmay make brief, weak attempts to stand followedby shaking of the limb muscles and collapse.Dosage and duration of action ofneuromuscular blocking drugsAtracuriumThe relatively short duration of action of activityand the lack of cumulative neuromuscular blockingeffect make atracurium particularly suitablefor use in horses in doses of 0.12–0.20 mg/kg(Hildebrand et al., 1986; 1989). The authors recommendan initial dose of 0.1 mg/kg followed, if thisdoes not produce the desired degree of relaxation

304 ANAESTHESIA OF THE SPECIESas indicated by train-of-four stimulation, by dosesof 0.01 mg/kg at 2 minute intervals until the blockis judged to be adequate (reduction of initialtwitch height). Edrophonium 0.5–1.0 mg/kg willantagonize any residual neuromuscular blockingeffects at the end of the procedure for which it isgiven and prior administration of atropine or glycopyrrolateis unnecessary provided the antagonistis injected slowly over more than 1 minute.Atracurium has also been given by continuousinfusion at 0.17 mg/kg/h after an initial bolusdose of 0.05 mg/kg (Hildebrand et al., 1989).Cardiovascular stability is good but there may besome slowing of heart rate after an initial increasein ABP in response to edrophonium.d-Tubocurarine chlorideIn halothane-anaesthetized animals with end-tidalconcentrations of halothane of about 1.0%, dosesof the order of 0.22–0.25 mg/kg d-tubocurarinechloride produce good relaxation with respiratoryarrest. The use of d-tubocurarine in horses sufferingfrom asthma or alveolar emphysema may beassociated with the production of bronchospasm,presumably due to histamine release. It is seldompossible to restore adequate spontaneous breathingby the use of anticholinesterases in less than35–40 minutes after d-tubocurarine has been givenin doses which produce respiratory arrest. Limbmovements are not seen during this period unlessthe depth of anaesthesia is allowed to becomeinadequate.Pancuronium bromideDuring light anaesthesia doses of 0.06 mg/kgproduce complete relaxation with apnoea of about20 min duration, but it is more usual to givedoses of 0.1 mg/kg to be certain of producingapnoea with complete relaxation of respiratorymuscles so that IPPV can be performed with thelowest possible airway pressures (Hildebrand &Howitt, 1984). The delay in achieving maximumeffect after i.v. injection is much less than that of d-tubocurarine chloride and no cases of relapse intoneuromuscular block have been encounteredfollowing neostigmine. The lack of histaminerelease makes this drug of value in cases where theadministration of d-tubocurarine might be dangerous.VecuroniumDoses of 0.1 mg/kg produce neuromuscular blockof some 20–30 minutes duration in horses lightlyanaesthetized with halothane. Although experiencewith this drug is limited it appears to be wellsuited for use in horses in that there is no evidenceof histamine release and complete antagonism ofblock is readily obtained about 20 minutes afterattainment of full relaxation with depression of thefirst twitch height in train-of-four stimulation ofthe superficial peroneal nerve. There then is noevidence of muscle weakness in the anaestheticrecovery period.Suxamethonium chlorideThe use of suxamethonium for casting andrestraint of horses is considered by the vast majorityof veterinary anaesthetists to be an extremelyinhumane practice, it is unnecessary and it isunsafe on pharmacological grounds. In the past,suxamethonium had a place in the provision ofvery short term muscle relaxation in anaesthetizedhorses but it has now been almost totally replacedby the short acting competitive blocking agentatracurium.Termination of neuromuscular blockThere is no effective antidote to suxamethonium,but neostigmine is an efficient antidote to the nondepolarizingrelaxants. In horses its use should bepreceded by the i.v. injection of 10 mg atropine sulphateor, better, 5 mg glycopyrrolate, and it is thengiven in incremental doses up to a total dose of10mg. A period of 2–3 minutes should be allowedbetween increments and the effect of each carefullyassessed before the next is given. Edrophoniumor neostigmine should be given whileIPPV is continued so that there is no danger ofhypoxia or hypercapnia because if given to hypoxicor hypercapnic animals neostigmine maycause serious arrhythmias. As a general rule, thedose of neostigmine needed to restore full spontaneousbreathing should be noted and a further

THE HORSE 305dose of half this amount given to be completely sureof full antagonism of all the effects of the relaxantdrug. Care must be taken not to confuse the weaknessof respiratory activity due to deep inhalationanaesthesia, hypothermia or metabolic alkalosisfrom excessive bicarbonate administration, withthat due to residual neuromuscular block.Intermittent positive pressure ventilation(IPPV)Careful thought is needed before IPPV is used inhorses. Since blood gas measurements havebecome readily available during anaesthesia,many anaesthetists have thought it advisable toinstitute IPPV whenever the PaCO 2 increases byabout 15 mmHg (2 kPa). Often in these circumstancesIPPV is commenced under inhalationanaesthesia without the use of muscle relaxants,the chest wall is stiff due to tone in the intercostalmuscles and diaphragm so that compliance is lowand high airway pressures are needed to expandthe lungs. These high inspiratory pressures raisethe mean intrathoracic pressure and can have amost deleterious effect on the circulation. LowerABPs during IPPV than during spontaneous ventilationhave often been erroneously attributed tolowering of the PaCO 2 . A decline in PaO 2 is frequentlyobserved in anaesthetized horses whenmuscle tone is returning after the use of neuromuscularblockers and airway pressures are increasedto maintain the respiratory tidal volume. In thesecases restoration of the PaO 2 requires nothingmore than the administration of a further dose ofthe relaxant.Normally, any increase in mean intrathoracicpressure is countered by peripheral venoconstrictionwhich raises the peripheral venous pressureand restores the pressure gradient to the right atrium.This has the effect of increasing the venousreturn and hence the CO. In hypovolaemic horses(e.g. many colic cases), and where the inhalationanaesthetic agents block the effect of sympatheticdischarge, the peripheral venoconstriction may beinadequate to counter the rise in mean intrathoracicpressure due to IPPV so that venous returnfalls and the CO declines. Diagnosis of hypovolaemiain horses is not always easy and evenwhen correctly diagnosed there may be insufficienttime for full replenishment of the blood volumeby transfusion before anaesthesia has to beinduced. For these reasons many anaesthetistsclaim that equine colic cases which may be hypovolaemicfare better if allowed to breathe spontaneouslyduring anaesthesia even if their PaCO 2rises to 60–70 mmHg (8.0–9.5 kPa). (In this connectionit must be noted that there is no evidence thatPaCO 2 increase to these levels is harmful—indeedit may be beneficial by increasing tissue perfusion.)The picture is, however, not quite as simpleas this for spontaneous ventilation must producean adequate tidal volume and many horses withbowel obstruction only ventilate satisfactorilyonce the abdomen has been surgically decompressed.If there is any delay in this decompressionit may be essential to institute IPPV as soon asanaesthesia is induced. IPPV is, of course, essentialfor thoracotomy or the repair of penetratingwounds of the chest.Ideally, monitoring of end-tidal CO 2 and/oranalysis of arterial blood samples drawn afterabout 20 minutes after the commencement of IPPVwill enable adjustments to be made to the imposedtidal volume and/or rate of ventilation so that anadequate PaO 2 is maintained with as near as possiblenormal PaCO 2 . Unfortunately, in many casesfacilities for blood gas estimation are not readilyavailable and the setting of the ventilator has to bemade from simple clinical observation of thehorse. Excursion of the chest wall should be somewhatgreater than might be expected in the spontaneouslybreathing horse, the respiratory frequencyshould be between 8 and 10 breaths/min, the tidalvolume about 10 ml/kg; the airway pressureshould be kept as low as is consistent with adequateexpansion of the chest wall and the inspiratorytime should be between 2 and 3 seconds.Experience is often the only reliable guide toproper pulmonary ventilation in any individualhorse. Whenever possible, the ABP should bemonitored so that any embarrassment of the circulationcan be recognized before too much harmresults from an unsuitable pattern of lung inflation.Assisted ventilation, in which the horse triggersthe ventilator which then delivers a prescribedtidal volume, is a very useful compromise inequine anaesthesia as long as the ventilator has a‘fail safe’ mechanism, whereby if the horse does

306 ANAESTHESIA OF THE SPECIESnot trigger a breath within a certain time, the ventilatorswitches to automatic mode.ANAESTHETIC RECOVERY PERIODIdeally horses should recover from anaesthesiacalmly and quietly, and in as fast a time as possible,but these aims cannot always be achieved. Thequality of recovery will depend on a number offactors including the sedative and anaestheticdrugs used throughout the perioperative process,the degree of postoperative pain, the comfort ofthe horse, its temperament, and limitation tostanding caused by surgery or onset of anaestheticinduced myopathy or neuropathy.It is important that the horse does not try to riseuntil it is able to do so. Following prolonged anaesthesiawith volatile agents it has now commonpractice to administer additional sedation (e.g.,xylazine at increments of 0.1 mg/kg i.v.) in theearly recovery period. Such sedation is less necessarywith halothane than with the newer agents orif, after suitable premedication, thiopental (whichprovides residual sedation) was used as the inductionagent.Horses anaesthetized under ‘field conditions’may be left to recover in a grassy field or on a thickstraw bed; no attempt should be made to inducean animal to stand before it tries to do so of its ownaccord. However, in equine hospitals animals areusually moved to a quiet, dimly-lit, well-paddedroom to minimize the chance of serious injury asthey regain their feet. It is important that the floorof this box is not slippery, even if wet. In some hospitalshorse are placed on thick soft mats – thismakes it difficult for the horse to regain sternalrecumbency, and this, together with the extra comfort,encourage it to remain recumbent until fullyready to stand. Assuming there are no surgicalcontraindications, an animal which has beensupine should be placed on its left side in therecovery area. However the positioning of an animalwhich has been lying on its side is controversial;turning to the other side enablesunder-perfused muscles to be reoxygenated, butresults in atelectasis of the lung lobes which arestill expanded.In major orthopaedic cases a decision may bemade to assist recovery but such recoveries shouldonly be carried out by experienced staff. Handlersprevent the horse from rising by controlling itshead, and by administering small doses ofxylazine as required, until the effects of the volatileagent have waned. The time required before thehorse should be allowed to attempt to risedepends on the kinetics of the volatile agentemployed – the authors sometimes restrain horsesgiven halothane for up to two hours, whilst followingdesflurane 30 minutes is sufficient. In manyhospitals ropes are used to assist the horse to risebut in most cases slings should not be used unlessthe horse is already accustomed to their use.In most cases adequate analgesia for the immediatepostoperative period will have been administeredat the end of anaesthesia. However, if notalready given, NSAIDs may be administered i.v.,and i.m. doses of pethidine (1 mg/ kg), do not addto recovery time (Taylor, 1986). Local nerve blocksgiven at the end of surgery on the digits for postoperativeanalgesia do not seem to cause problemsfor the horse attempting to stand up. Unlesscatheterized, the bladder of male animals givenfluid i.v. during operation may become distendedand cause considerable abdominal pain; catheterizationof the bladder produces immediate relief.This problem does not occur in female animalsbecause urine will seep from the bladder duringanaesthesia, but catheterization will prevent urinefrom spilling on to the floor.The timing of removal of the endotracheal tubeis controversial. Some anaesthetists leave the tubein place until the horse has arisen, but this is onlypossible with an adequate mouth gag, and eventhen authors have seen recovering animal occludethe tube by biting on it. Respiratory obstructioncaused in this way can be difficult to relieve andexpensive tubes may be ruined. In addition, stimulationof the trachea by the tube has been associatedwith cardiac arrest, presumably through avagal mechanism, as anaesthesia lightens.Following prolonged anaesthesia, respiratoryobstruction is frequently observed after removal ofthe endotracheal tube, probably due to hypostaticcongestion of the nasal and pharyngeal mucousmembranes, and the horse makes a characteristicsnoring noise. Ideally, it is prevented by keepingthe horse’s head slightly elevated during anaesthesia,but if this has not been done, the obstruction

THE HORSE 307can be relieved by passing a small-bore endotrachealtube through one nostril. Unless properlysecured such a tube may be aspirated into thetracheobronchial tree.A rare complication in recovery is obstructiondue to laryngeal paralysis; this probably resultsfrom neuronal damage from stretching the headon the neck. Should this occur the horse willobstruct as soon as the nasal tube is removed,and an emergency tracheotomy may be required.O 2 can be given through the nasal endotrachealtube, although to produce any significantimprovement of PaO 2 , it must be administeredinto the trachea at a flow rate of at least 15 1/min.It has been suggested that an O 2 demand valvemay be used to administer oxygen during therecovery period (Reibold et al., 1980) but othershave found this rather unsuitable (Watney et al.,1985).REFERENCESAguiar, A., Hussni, C.A., Luna, S.P. et al. (1993) Propofolcompared with propofol/guaifenesin afterdetomidine premedication. Journal of VeterinaryAnaesthesia 20: 26–28.Aida, H., Mizuno, Y., Hobo, S. et al. (1994) Determinationof the minimal alveolar concentration (MAC)and physical response to sevoflurane inhalationin horses. Journal of Veterinary Medical Science56: 1161–1165.Aida, H., Mizuno, Y., Hobo, S. et al. (1996)Cardiovascular and pulmonary effects ofsevoflurane anesthesia in horses. VeterinarySurgery 25: 164–170.Aida, H., Kawashima, K., Yokota, M. et al. (1997)Recovery characteristics of sevoflurane anesthesia inracehorses. Proceedings of the 6th International Congressof Veterinary Anaesthesiology, p. 125.Alexander, F. and Collett, R.A. (1974) Pethidine in thehorse. Research in Veterinary Science 17: 136–137.Alibhai, H.I. and Clarke, K.W. (1996) Influence ofcarprofen on minimum alveolar concentration ofhalothane in dogs. Journal of Veterinary Pharmacologyand Therapeutics 19: 320–321.Alitalo, I. (1986) Clinical experiences with Domosedanin horses and cattle. A Review. Acta VeterinariaScandinavica Supplement 82: 193–196.Amadon, R.S. and Craige, A.H. (1936) Observations onthe use of bulbocapnine as a soporific in horses.Journal of the American Veterinary Medical Association41: 737–754.Archer, R.K. (1947) Pethidine in Veterinary Practice.Veterinary Record 59: 401– 402.Beadle, R.E., Robinson, N.E. and Sorensen, P.R. (1975)Cardiopulmonary effects of postitive end-expiratorypressure in anesthetized horses. American Journal ofVeterinary Research 36: 1435–1438.Bettschart-Wolfensberger, R., Taylor, P.M., Sear, J.W. et al.(1996) Physiologic effects of anesthesia induced andmaintained by intravenous administration of aclimazolam-ketamine combination in poniespremedicated with acepromazine and xylazine.American Journal of Veterinary Research 57: 1472– 1477.Bettschart, W.R., Clarke, K.W., Vainio, O. et al. (1999)Pharmacokinetics of medetomidine in ponies andelaboration of a medetomidine infusion regime whichprovides a constant level of sedation. Research inVeterinary Science 67: 41– 46.Bettschart-Wolfensberger, R. (1999a) Total intravenousanaesthesia in horses using medetomidine andpropofol. PhD thesis. London: Royal VeterinaryCollege, University of London.Brearley, J.C., Jones, R.S., Kelly, D.F. et al. (1986) Spinalcord degeneration following general anaesthesia in aShire horse. Equine Veterinary Journal 18: 222–224.Bryant, C.E., England, G.C. and Clarke, K.W. (1991)Comparison of the sedative effects of medetomidineand xylazine in horses. Veterinary Record 129: 421– 423.Carroll, G.L., Hooper, R.N., Slater, M.R. et al. (1998)Detomidine-butorphanol-propofol for carotid arterytranslocation and castration or ovariectomy in goats.Veterinary Surgery 27: 75–82.Clarke, K.W. and Hall, L.W. (1969) Xylazine–a newsedative for horses and cattle. Veterinary Record85: 512–517.Clarke, K.W. and Taylor, P.M. (1986) Detomidine: a newsedative for horses. Equine Veterinary Journal18: 366– 370.Clarke, K.W., Taylor, P.M. and Watkins, S.B. (1986)Detomidine/ketamine anaesthesia in the horse.Acta Veterinaria Scandinavica (Suppl): 82: 167–179.Clarke, K.W. (1988) D. Vet. Med. Thesis. London:University of London.Clarke, K.W. and Paton, B.S. (1988) Combined use ofdetomidine with opiates in the horse. EquineVeterinary Journal 20: 331– 334.Clarke, K.W. and Gerring, E.E.L. (1990) Detomidine as asedative and premedicant in the horse. AmericanAssociation of Equine Practitioners 35: 629–635.Clarke, K.W., England, G.C.W. and Goossens, L. (1991)Sedative and cardiovascular effects of romifidinealone and in combination with butorphanol in thehorse. Journal of Veterinary Anaesthesia 18: 25–29.Clarke, K.W., Alibhai, H.I.K. and Hammond, R.A.(1996) Desflurane anaesthesia in the horse: Minimalalveolar concentration following induction withxylazine and ketamine. Journal of VeterinaryAnaesthesia 23: 56– 59.Clarke, K.W., Song, D.Y., Alibhai, H.I. et al. (1996a)Cardiopulmonary effects of desflurane in ponies, afterinduction of anaesthesia with xylazine and ketamine.Veterinary Record 139: 180–185.

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310 ANAESTHESIA OF THE SPECIEShalothane-anesthetized ponies. American Journal ofVeterinary Research 59: 1463–1472.Lee, Y.H., Clarke, K.W. and Alibhai, H.I. (1998a) Thecardiopulmonary effects of clenbuterol whenadministered to dorsally recumbent halothaneanaesthetisedponies—failure to increase arterialoxygenation. Research in Veterinary Science65: 227–232.Lee, Y.H., Clarke, K.W. and Alibhai, H.I. (1998b) Effectson the intramuscular blood flow andcardiopulmonary function of anaesthetised ponies ofchanging from halothane to isoflurane maintenanceand vice versa. Veterinary Record 143: 629–633.Lindsay, W.A., McDonell, W. and Bignell, W. (1980)Equine postanesthetic forelimb lameness:intracompartmental muscle pressure changes andbiochemical patterns. American Journal of VeterinaryResearch 41: 1919–1924.Lindsay, W.A., Pascoe, P.J., McDonell, W.N. et al. (1985)Effect of protective padding on forelimbintracompartmental muscle pressures in anesthetizedhorses. 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Anaesthesia of cattle 12INTRODUCTIONCattle are by no means good subjects for heavysedation or general anaesthesia. Regurgitationfollowed by aspiration of ruminal contents intothe lungs can easily occur. Once a ruminant animalis in lateral or dorsal recumbency, theoesophageal opening is submerged in ruminalmaterial, normal eructation cannot occur, and gasaccumulates. The degree of bloat depends on theamount of fermentation of the ingesta and on thelength of time that gas is allowed to accumulate.Gross distension of the rumen becomes a hazard ifanaesthesia or recumbency is prolonged and regurgitationcan follow from this. In addition, theweight of the abdominal viscera and their contentsprevents the diaphragm from moving freely oninspiration and ventilation becomes shallow, rapidand inefficient for gas exchange within the lungs.The danger of regurgitation and inhalation ofingesta is always present but the likelihood of itoccurring can be minimized by:1. Withholding all food for 24 to 48 hoursbefore anaesthesia. Optimum duration forstarvation is up for discussion, with somerecommending that 24 hours is not only sufficientbut also produces the best consistency of rumencontents to minimize regurgitation. A longerperiod of starvation may result in formation of amore liquid ruminal content which may beregurgitated more easily.2. Withholding water for 8 to 12 hours beforeanaesthesia.3. When the animal is in lateral recumbencyduring anaesthesia arranging that the occiput isabove general body level and that the head slopesso that saliva and any regurgitated material runsfreely from the mouth (Fig. 12.1).4. At the end of anaesthesia, cleaning solidmaterial from the pharynx and leaving theendotracheal tube in the trachea with the cuffinflated until the animal is in sternal recumbency,is swallowing and, most importantly, can withdrawits tongue back into its mouth.An additional procedure to prevent regurgitationthat has been tried but not often used is topass a modified stomach tube as far down theoesophagus as possible. The tube has a balloonfirmly attached to its end that can be inflated toFIG.12.1 Animal’s head inclined over a support to allowsaliva and any regurgitated rumenal content to drain outof the mouth.315

316 ANAESTHESIA OF THE SPECIESobstruct flow of ingesta from the rumen into thepharynx.Regurgitation occurs during both light anddeep anaesthesia so that it is probable that twomechanisms are involved in the process. Duringlight anaesthesia ingesta may pass up the oesophagusinto the pharynx as a result of an active, butuncontrolled, reflex mechanism. It is then a matterof chance whether or not the protective reflexes,e.g. laryngeal closure, coughing, etc., are activeand can or cannot prevent aspiration. Fortunately,laryngeal closure often occurs but, as hypoxiadevelops, at some point the animal will take alarge breath and any ingesta accumulated in thepharynx will be aspirated. The order in which thereflexes of laryngeal closure, coughing, swallowing,and regurgitation disappear as anaesthesia isdeepened differs from one anaesthetic drug combinationto another but the relative safety of thevarious agents is not documented. During deepanaesthesia, on the other hand, regurgitation is apassive process. The striated muscle of the oesophagusloses its tone and any increase in the intraruminalpressure – whether from pressure on theabdominal wall from a rope or belly band or fromgas accumulation in the rumen itself – may forceingesta up into the pharynx. The protective reflexesare not active and aspiration may occur easily.Tracheal intubation is not always performed inall sedated or anaesthetized recumbent bovine animalsand regurgitation does not always occur.However, some animals will regurgitate, and thishas an unreasonably high risk for fatal outcome.Should regurgitation occur during the induction ofanaesthesia before endotracheal intubation hasbeen accomplished, the endotracheal tube may beimmediately passed into the oesophagus and itscuff inflated so that the regurgitated material passesalong the tube and out of the mouth. The tracheacan then be intubated with a second tube,taking care to cover the end of the tube to avoidscooping material into its lumen. In actuality, thepresence of one endotracheal tube in the pharynxoften makes passage of a second tube nearlyimpossible due to the small size of the bovinepharynx. One option is to intubate the tracheawith a stomach tube and attempt to feed the secondendotracheal tube over the stomach tube. Analternative is to wait until the flow of ingesta stops,remove the tube from the oesophagus and torapidly intubate the trachea. However, if theconditions initiating the regurgitation such asropes tight around the thorax and abdomenhave not been removed, or the depth of anaesthesiais light, regurgitation may recommence duringthe removal of the endotracheal tube from theoesophagus.Salivation continues as a copious flow throughoutgeneral anaesthesia but the loss of saliva isunlikely to produce a significant effect onacid–base status. Antisialagogues are not of muchuse for they make the secretion more viscid innature and do not significantly reduce its production.It is important to arrange the head of theanaesthetized animal so that saliva drains from themouth and does not accumulate in the pharynx.Intubation with a cuffed endotracheal tube willprevent inhalation of saliva.In two reports involving restraint of unsedatedcows or bulls in dorsal or lateral recumbency, adecrease in PaO 2 from an average standing valueof 11.4 kPa (86 mmHg) to less than 9.3 kPa (70mmHg) was measured, with a decrease to below6.6 kPa (50 mmHg) in some individuals (Semrad etal., 1986; Klein & Fisher 1988). Arterial PCO 2remained at or slightly below 5 kPa (38 mmHg). Inanother investigation of cows from which foodwas withheld for 18 h, mean PaO 2 in standing animalswas 14.5 kPa (109 mmHg) (Wagner et al.,1990). Significant decreases in PaO 2 occurred inboth lateral and dorsal positions but only in dorsalrecumbency did values decrease to below 9.3 kPa(70 mmHg). These changes indicate that even inunsedated cattle, recumbency creates abnormalitiesof ventilation and perfusion that are notcounter-balanced by normal compensatory mechanisms.It is not surprising that cattle sedated withxylazine and breathing air will develop decreasedoxygenation or hypoxaemia (DeMoor & Desmet,1971; Raptopoulos & Weaver 1984).Withholding feed before sedation and anaesthesiamay reduce pressure on the diaphragm,limit lung collapse and modify the decrease inPaO 2 . In a study of fed and non-fed cows anaesthetizedwith halothane and breathing oxygen,cows fed before anaesthesia had a progressivedecrease in PaO 2 , reaching hypoxaemic levels afteran hour of anaesthesia, whereas cows that were

CATTLE 317starved before anaesthesia were well oxygenated(Blaze et al., 1988). Severe hypercapnia was measuredin both groups with a greater increase measured inthe fed cows. Thus, hypoxaemia may develop inrecumbent non-starved cattle even when inhalinghigh O 2 concentrations but supplementation ofinspired air with O 2 may prevent hypoxaemia ifthe cow has been starved first. Respiratory acidosisusually develops in anaesthetized cattle.Normal values for cardiovascular parametersin unsedated healthy cattle are approximately73 ± 14 beats/min (mean ± SD) for heart rate,150 ± 27 mmHg for mean arterial pressure, and64 ± 14 ml/kg/min for cardiac output (Wagneret al., 1990). Withholding feed for 48 h has beendetermined to cause significant decreases in heartrates in cattle (Rumsey & Bond, 1976; McGuirket al., 1990).RESTRAINTThe majority of bovine clinical surgery is carriedout under local analgesia, frequently in the standinganimal. Surgical procedure is made easier byuse of appropriate sedation and/or restraining‘crushes’ or ‘chutes’. Ropes are useful additions forrestraining sedated or unsedated cattle and anyonein cattle veterinary practice soon becomesexpert at tying quick-release knots, tying bowlineknots for rope loops, applying Reuff’s method ofcasting a mature bovine by squeezing with a neckloop and two half-hitches around the body, andassembling figure of eight ties to secure flexedfront and hind limbs.ElectroimmobilizationElectrical devices are available to immobilize cattleby causing muscle tetanus from application of anelectrical current between electrodes at the lip andrectum. There are concerns that this technique isneither humane nor analgesic. Holstein cowstrained to be lead with a halter and enter a set ofstocks were observed for behavioural and physiologicalresponses to either immobilization byapplication of an electric current for 30 s from acommercially available electroimmobilizer or toan intramuscular injection with an 18 gauge needle(Pascoe, 1986). The electrical immobilizationwas associated with significant aversive behaviourand evidence of distress and the results led theauthors to believe that electroimmobilization wasa strong noxious stimulus that was rememberedfor several months.SEDATIONAGENTS USED IN BOVINE ANAESTHESIAXylazineXylazine has for a long time been the most effectivesedative available for cattle. The dose rate ofxylazine in cattle, 0.02–0.20 mg/kg, with the highestdose intended for i.m. use, is one-tenth of thatused in horses. Intravenous injection results indeeper sedation than i.m. administration. Cattlemay assume recumbency even at the lowest doserates, although breed differences in sensitivity toxylazine have been reported. In an investigationcomparing Hereford and Holstein cattle, 84% ofHerefords spontaneously lay down after xylazineadministration, whereas only 22% of Holsteins didso (Raptopoulos & Weaver, 1984). Furthermore,the average duration of recumbency in the Herefordswas 90 min compared with 50 min in theHolsteins. The environmental conditions underwhich xylazine is administered may influence theresponse. In a study comparing the effects ofxylazine in Holstein heifers under a thermoneutralcondition compared with a hot environment (temperatureapproximately 33 °C and relative humidity63%), the time to standing was increased from41 min to an average of 107 min during heat stress(Fayed et al., 1989). Xylazine causes contraction ofthe bovine uterus similar to oxytocin (LeBlancet al., 1984), and premature birth has been reportedafter administration to heavily pregnant cows.Today it is generally acknowledged that use ofxylazine in pregnant cows in the last trimester ofpregnancy is contraindicated.Xylazine may cause mild to severe decreases inPaO 2 and moderate increases in PaCO 2 in maturecattle (DeMoor & Desmet, 1971; Raptopoulos &Weaver, 1984). Xylazine administration inducesbradycardia, decreased MAP and CO, andincreased peripheral resistance (Campbell et al.,1979). Campbell et al. (1979) also noted second

318 ANAESTHESIA OF THE SPECIESdegree atrioventricular heart block in one out offive calves receiving xylazine.Xylazine has a number of side effects that mayhave an adverse effect on the animal. It abolishesthe swallowing reflex so that regurgitation canresult in pulmonary aspiration. The inability of thecow or bull to withdraw its tongue into its mouthand swallow may persist until after the animalregains the standing position. Thus, it is advisableto withhold food and water from cattle before givingxylazine. Gastrointestinal motility is decreasedand bloat may develop, while diarrhoea may beobserved 12–24 hours after sedation (Hopkins,1972). Hyperglycaemia persisting for about10 hours develops after xylazine administrationand this is associated with a decrease in seruminsulin concentration (Symonds & Mallinson,1978; Eichner et al., 1979). The decrease in seruminsulin is believed to be due to a decrease inproduction (Fayed et al., 1989). Increased urineproduction occurs within 30 minutes of administrationand continues for two hours (Thurmonet al., 1978) due to suppression of antidiuretic hormone(ADH) release. Use of xylazine in animalswith urethral obstruction may be responsible forrupture of the urinary bladder or urethra.Minor surgical procedures have been performedon cattle sedated with xylazine but,whenever possible, local infiltration techniques ornerve blocks should be utilized to ensure sufficientanalgesia.DetomidineIn contrast to xylazine, the dose rates for detomidinein cattle are similar to those used in horses.Dose rates of 0.03–0.06 mg/kg i.m. have been usedin clinical trials, however lower doses may providesufficient sedation for combination with local analgesictechniques for surgery. Elimination is mainlyby metabolism as there is negligible excretion ofthe drug in urine. No detomidine was detectable inmilk 23 h after dosing and tissue concentrationsmeasured 48 h after dosing were less than 3% ofthe original dose (Salonen et al., 1989). Detomidine,0.04 and 0.06 mg/kg, increases electrical activity ofthe bovine uterus, although administration ofdetomidine, 0.05 mg/kg, to a group of pregnantcows was not followed by abortions (Vainio, 1988).A lower dose rate of detomidine, 0.02 mg/kg,decreased electrical activity of the uterus and sedationat this dose rate may be safe in the pregnantanimal (Vainio 1988).The pharmacologic effects of detomidine in cattleare very similar to those of xylazine in that itcauses bradycardia, hyperglycaemia, and increasedurine production. An exception is thatdetomidine causes arterial hypertension which isdose-dependent in duration.MedetomidineDeep sedation without recumbency can be obtainedwith intravenous doses of medetomidine,0.005 mg/kg, while 0.01 mg/kg produces recumbencyand sedation equivalent to that obtainedwith intravenous doses of 0.1–0.2 mg/kg xylazine(G. C. W. England and K. W. Clarke, unpublishedobservations). Medetomidine, 0.04 mg/kg, hasbeen given intravenously alone or with ketaminefor anaesthesia in calves (Raekallio et al., 1991;Ranheim et al., 1998). Medetomidine, 0.015 mg/kg,has been administered by epidural injection foranalgesia in cows (Lin et al., 1998).Antagonists to the α 2 adrenoceptor agonistsAs prolonged recumbency causes so many problemsin cattle, the availability of α 2 adrenoceptorantagonists is of particular value. These antagonistsnot only cause the animal to awaken, they alsoantagonize the majority of the side effects of theagonists, including restoring ruminal motility tonormal.Almost all the α 2 adrenoceptor antagonistshave been used in cattle sedated with xylazine.Yohimbine, 0.125 mg/kg, with aminopyridine,0.3 mg/kg, will awaken cattle sedated with0.2–0.3 mg/kg of xylazine, but will not restore anormal state of consciousness. Idazoxan at dose of0.01–0.10 mg/kg is reported to be effective againstxylazine in calves, with no relapse to sedation.Tolazoline at 0.2 mg/kg reverses the suppressionof ruminal motility induced by xylazine but higherdoses, 0.5–2.0 mg/kg, are required for full reversalof sedation. Care must be taken to administer tolazolineslowly as intravenous injection has beenassociated with abrupt adverse haemodynamic

CATTLE 319changes. One experimental study of xylazineadministered by intramuscular and lumbosacralepidural routes concluded that the technique didnot provide adequate analgesia for umbilical surgeryin calves (Lewis et al., 1999). In this study,reversal of sedation with tolazoline caused transientsinus bradycardia and sinus arrest, accompaniedby severe systemic arterial hypotension.Atipamezole in doses of 25 and 50 µg/kg, intravenouslyor intramuscularly, causes awakening incows sedated with 0.2 mg/kg of xylazine, withrestoration of ruminal motility to normal. Twohours later some relapse occurs although resedationshould not be so deep as to cause recumbency.Relapse does not occur after i.m. injection of theantagonist. Atipamezole, 60 µg/kg, given either asthe entire dose i.v. or as half the dose i.v. and halfi.m. to antagonize medetomidine in calves resultsin a rapid smooth recovery to ambulation(Raekallio et al., 1991). Calves sedated with medetomidine,0.04 mg/kg, and injected with atipamezole,200 µg/kg i.v. 60 minutes later, becameresedated on average 80 min after the injection ofatipamezole and this lasted an average of 240 min(Ranheim et al., 1998). These authors suggestedthat the relapse into sedation could not be explainedby differences in pharmacokinetic parametersof medetomidine and atipamezole. It may bethat the elimination of medetomidine from thesites of action is slower than elimination of thedrug from plasma. Atipamezole given to unsedatedcattle, or as medetomidine sedation is waning,may induce a state of hyperactivity, kickingand bucking.AcepromazineAcepromazine may be given in doses of0.05 mg/kg i.v. or 0.1 mg/kg i.m. to induce mildtranquillization. Acepromazine will decrease thedose rate of subsequently administered anaestheticsand may increase the risk of regurgitation.Chloral hydrateAlthough some of the more recently introducedagents, such as the α 2 adrenoceptor agonistxylazine, may have some advantages, includingeasier administration, chloral hydrate is still aperfectably acceptable, inexpensive sedative foradult cattle. It may be given by mouth or i.v. injection.To obtain a recumbent, very lightly unconsciousadult cow, the drug is usually administeredby drench, or preferably by stomach tube, in dosesof 30–60 g as a 1 in 20 solution in water. Sedationattains its maximum depth in a period of 10–20min and local analgesics may be injected for nerveblocks while sedation is developing. As cows cangenerally be cast and restrained without difficulty,i.v. administration will generally be in this positionwith the head and neck extended. The externaljugular vein can be readily distended by fingerpressure and the use of choke cords is unnecessarilydistressful for the animal. The doserequired is between 80 and 90 mg/kg of a 10%solution and it should be remembered that narcosiswill continue to deepen after the i.v. injection iscompleted. The induction and recovery periodsare excitement free.Young bulls present no particular difficultiesprovided their temperament is such that they canbe safely and effectively restrained for drenchingor precise i.v. injection. In older bulls the precisei.v. injection of drugs in the standing position maynot only be uncertain on account of difficulties insatisfactorily introducing the needle into the veinbut sometimes impossible because of movementby the animal.In many instances the temperament of the bullis such that large doses have to be given by mouthin order to obtain sufficient sedation to allowapplication of casting tackle. The further administrationof the drug by the i.v. route after castinggives rise to danger of overdose consequent oncontinued absorption from the stomach. When,without any previous medication, chloral hydrateis given to a bull by i.v. injection at the usual rate,the dose required to induce deep narcosis is thesame as for the big cow – about 90–100 mg/kg.When the drug is given by the mouth a dose of140–200 g (or even more) may be required toinduce a degree of sedation whereby the animalcan be handled safely and even after such a quantitythe animal may still be able to stand.The bull which is running free in the yard or aloose-box may be quite dangerous even toapproach. In such cases it is generally advised thatdrinking water be withheld for 36 hours and that

320 ANAESTHESIA OF THE SPECIESthe animal then be offered water containing 90 to120 g of chloral hydrate in 12 litres. It is often takenand, if it is, the degree of sedation is such that, withcare, the bull can be approached and a leading poleapplied.PentobarbitalNervous or excitable cattle may be restrained bythe slow i.v. injection of a 20% solution of pentobarbital.To make the animal sway slightly on its hindlegs while being able to walk unaided, a dose of1–2 g is needed for the adult cow. A dose of about3g/500 kg usually makes an adult cow recumbentand almost unconscious.Small doses (15–20 ml of a 6.5% solution, i.e.1.00–1.25 g) may be given to prolong narcosisinduced with chloral hydrate. It is injected i.v. assoon as the chloral hydrate effect becomes inadequateand provided the injection is made slowly,and to effect, no harmful effects occur. The period ofrecumbency is much less than if additional doses ofchloral hydrate are administered and recovery isnot associated with struggling and excitement.More than one injection of pentobarbital may begiven during the course of long operations.ButorphanolAdministration of butorphanol to healthy unsedatedcows will not predictably induce sedationand may induce behaviour changes including restlessnessand bellowing. Butorphanol, 0.02–0.03 mg/kg, may provide sedation in cattle thatare sick and may increase the quality of sedationwhen administered in conjunction with xylazine.Butorphanol can be detected in the milk for up to36 hours following administration (Court et al.,1992)LOCAL ANALGESIASPECIAL NERVE BLOCKSAuriculopalpebral nerve blockThis nerve supplies motor fibres to the orbicularisoculi muscle. The nerve runs from the base of theear along the facial crest, past and ventral to theFig.12.2 Auriculopalpebral nerve block.eye, giving off its branches on the way. This blockis used to prevent eyelid closure during examinationor surgery of the eye. It does not provide analgesiato the eye or eyelids and should be used inconjunction with topical analgesia or other nerveblocks for painful procedures.The needle is inserted in front of the base of theear at the end of the zygomatic arch until its pointlies at the dorsal border of the arch (Fig. 12.2).About 10–15 ml of 2% lignocaine is injectedbeneath the fascia at this point.Cornual nerve blockThe horn corium and the skin around its basederive their sensory nerve supply from a branch ofthe ophthalmic division of the 5th cranial nerve.The nerve emerges from the orbit and ascends justbehind the lateral ridge of the frontal bone. Thislatter structure can be readily palpated with thefingers. In the upper third of the ridge the nerve isrelatively superficial, being covered only by skinand a thin layer of the frontalis muscle.The site for injection is the upper third of thetemporal ridge, about 2.5 cm below the base of thehorn (Fig. 12.3). The needle (18 gauge, 2.5 cm long)is inserted so that its point lies 0.7–1.0 cm deep,immediately behind the ridge, and 5 ml of 2% lignocainesolution injected. The needle must not beinserted too deeply, otherwise injection will bemade beneath the aponeurosis of the temporalmuscle and the method will fail. In large animals

CATTLE 321PterygoidcrestCoronoid processof mandibleSupraorbitalprocessFIG.12.3 Injection of the nerve to the horn core.Insome animals the branch to the caudal part leaves theparent trunk proximal to the normal site for injection.with well developed horns, a second injectionshould be made about 1 cm behind the first toblock the posterior division of the nerve (Fig. 12.3).Loss of sensation develops in 10–15 minutes andlasts about 1 hour. This nerve block has beenwidely used for the dishorning of adult cattle butthe block is not always complete. Variability in thecurvature of the lateral ridge of the frontal bonemakes exact determination of the site of the nervedifficult. In a struggling animal, it may be difficultto ensure that the point of the needle is at the correctdepth. A third injection may be required inadult cattle with well developed horns; it is madecaudal to the horn base to block the cutaneousbranches of cervical nerves.Petersen eye blockForamenorbitorotundumNeedle directionfor Petersen blockA 22 gauge, 2.5 cm needle is used to infiltrate localanalgesic solution subcutaneously, about 5 ml of2% lignocaine, within the notch formed by thesupraorbital process cranially, the zygomatic archventrally and the coronoid process of the mandiblecaudally (Fig. 12.4). A 12 or 14 gauge, 2.5 cm needleplaced as far rostral and ventral as possible in thedesensitized skin of the notch serves as a cannulaand a 18 gauge, 10 or 12 cm needle is introducedthrough it. The long needle is directed in a horizontaland caudal direction until it strikes the coronoidprocess of the mandible. It is then redirectedtowards the pterygopalatine fossa rostral to theorbitorotundum foramen at a depth of about 8–10cmfrom the skin and 10–15 ml of 2% lignocaine solutioninjected. This blocks the oculomotor, trochlear,abducens nerves and the three branches of thetrigeminal nerve as they emerge from the foramenorbitorotundum. The needle is withdrawn to thesubcutaneous tissue and redirected caudally andlaterally to block the auriculopalpebral nerve onthe zygomatic ridge by the injection of 5–10 ml ofthe local analgesic solution. The Petersen techniquerequires more skill to perform than a retrobulbarblock but it may be safer.Peribulbar and retrobulbar blockSite forauriculopalpebralnerve block(zygomatic arch)FIG.12.4 Schematic drawing of the Petersen nerve blockto block the nerves emerging from the foramenorbitorotundum,together with the auriculopalpebralnerve block on the zygomatic ridge.This is an alternative tothe retrobulbar block but requires more skill to perform.Retrobulbar injection is achieved by introductionof a curved needle through the skin about 1 cmlateral to the lateral canthus, or through the conjunctiva.The needle is first directed straight backand away from the eyeball until the point is beyondthe globe and then turned inward to penetrate themuscle cone. When no blood is obtained after aspiration,lignocaine is deposited behind the eye.Peribulbar anaesthesia is produced by insertingthe needle and injecting lignocaine in 2 to 4 quadrantswithin the orbit but outside the ocular

322 ANAESTHESIA OF THE SPECIESmuscles. Injection of 20–30 ml of 2% lignocaine (orits equivalent) will produce corneal analgesia, mydriasis,and proptosis and paralysis of the eyeball.Anaesthesia is produced after spread of the anaestheticagent; thus a larger volume of lignocaine isrequired for peribulbar anaesthesia, the onset ofblock is longer, and the larger volume of solutioncauses a greater increase in ocular pressure.Recommendations vary over the use of sharphypodermic or blunt (e.g. spinal needle) needlesfor ocular blocks, but penetration of the globe hasbeen reported in human patients with both sharpand blunt needles (Hay, 1991; Wong, 1993). Bluntneedles are not considered to be safer thansharp needles. Visual outcome is not a factor whenpenetration of the globe occurs during nerve blockfor enucleation. However, bacterial contaminationof the orbit is possible.Potentially adverse effects of both the Petersenblock and the retrobulbar block include bradycardia,hypotension, asystole, respiratory depression,apnoea, perforation of the globe and intraorbital orretrobulbar venous haemorrhage. Symptoms oflocal anaesthetic spread to the central nervous systemvary but respiratory arrest is a usual sign ofbrainstem anaesthesia. When the block is used forother purposes, care must be taken to ensure thatthe corneal surface does not become dry becauseof loss of tear formation for several hours.Inverted L blockInfiltration of the skin, subcutaneous and deepertissues in an inverted L shape with 60 ml of 2% lignocainesolution is a commonly used technique toprovide analgesia for a flank laparotomy in astanding cow (Chapter 10). It is also used inrecumbent animals to block the site for a paramedianincision, or repeated in a mirror image toform a U shape and analgesia for a midline incision.Injections must be made both subcutaneouslyand down to the peritoneum to produce atotal block. The block can be achieved by makingisolated injections at intervals of about 1 cm, whichrelies on lateral diffusion of the analgesic solution.Alternatively, a wall of local analgesic solution canbe created by inserting a long needle to its depth,and injecting anaesthetic solution in a steadystream as the needle is withdrawn.Paravertebral nerve blockParavertebral block involves the perineural injectionof local analgesic solution about the spinalnerves as they emerge from the vertebral canalthrough the intervertebral foramina. This techniqueis commonly used to provide analgesia forlaparotomy. It offers a major advantage over use offield infiltration in that the abdominal wall includingthe peritoneum is more likely to be uniformlydesensitized. Additionally, the abdominal wall isrelaxed.The area of the flank bounded cranially by thelast rib, caudally by the angle of the ilium and dorsallyby the lumbar transverse processes, is innervatedby the thirteenth and first and second lumbarnerves. In addition, the third lumbar nerve,although it does not supply the flank, gives off acutaneous branch which passes obliquely backwardsin front of the ilium. Operations involvingthe ventral aspect of the abdominal wall willrequire additional desensitization of the dorsalnerves cranial to the thirteenth. The last dorsal andfirst lumbar intervertebral foramina in cattle areoccasionally double. The last dorsal foramen liesimmediately caudal to the head of the last rib andon a level with the base of the transverse process ofthe first lumbar vertebra. The lumbar foramina arelarge and are situated between the base of the transverseprocesses and approximately on the samelevel. The spinal nerves, after emerging from theforamina, immediately divide into a smaller dorsaland a larger ventral branch. The dorsal branchsupplies chiefly the skin and muscles of the loins,but some of its cutaneous branches pass a considerabledistance down the flank. The ventral branchpasses obliquely ventrally and caudally betweenthe muscles and comprises the main nerve supplyto the skin, muscles, and peritoneum of the flank.The ventral branch is also connected with the sympatheticsystem by a ramus communicans. Paralysisof the nerves at their points of emergencefrom the intervertebral foramina will provokedesensitization of the whole depth of the flankwall and complete muscular relaxation. Block ofthe rami communicantes will result in splanchnicvasodilatation and potential for hypotension.The number of nerves to be blocked willdepend on the site and extent of the proposed inci-

CATTLE 323FIG.12.5 Regions of the flank involved afterparavertebral block of the respective nerves.sion. The areas involved by blocking of respectivenerves are illustrated in Fig. 12.5. Therefore, forrumenotomy, using an incision parallel with andabout 7 cm caudal to the last rib, analgesia of thethirteenth thoracic and first and second lumbarnerves is required. The third lumbar nerve must beblocked for a more caudal incision and for relaxationof the internal oblique muscle.A number of different techniques for blockingthe respective nerves have been described but themost reliable relies on directing the needle towardsthe cranial border of the transverse process of thevertebra behind the nerve to be blocked. For example,to block the 1st lumbar nerve the needleshould be directed to strike the cranial broder ofthe 2nd lumbar vertebra about 5–6 cm from theanimal’s midline. At such sites the cranial bordersof the transverse processes are usually in the samecross sectional plane of the body as the mostprominent parts of their lateral borders.To block the thirteenth thoracic and first, secondand third lumbar nerves skin weals should beraised in line with the most obvious parts of thetransverse processes of the second, third andfourth lumbar vertebrae, 5–6 cm from, the midlineof the body. Location of the transverse process ofthe first lumbar vertebra is usually difficult (particularlyin well-muscled or obese animals) so inmost cases the site for infiltration around the thirteenththoracic nerve is found by simple measurement.The distance between the skin weals overthe second and third lumbar transverse processesis measured and another skin weal is produced ata distance equal to this, cranial to the anteriorweal, to mark the site where the needle is to beintroduced to strike the cranial border of the firstlumbar transverse process. A stout needle (7 cmlong, 3 mm bore) is inserted through each skinweal and the underlying longissimus dorsi muscleinfiltrated with 2–3 ml of 1% lignocaine (lidocaine)or other local analgesic solution as they areadvanced to a depth of about 4 cm from the skinsurface. This infiltration is omitted by some workersbut it does serve to counteract spasm of thelongissimus dorsi during the subsequent insertionof the longer needle used to deposit analgesicsolution around the main nerve trunks. The needlesused for injection around the nerves (10 cmlong, 2 mm bore) are introduced, after an appropriatepause, through the holes made in the skin bythe stout needles used for infiltration of the longissimusdorsi muscle, and advanced to strike theanterior border of the transverse process. Eachneedle is then redirected cranially over the edge ofthe transverse process and advanced until it is feltto penetrate the intertransverse ligament. Penetrationof the intertransverse ligament is mademore obvious if the needles used have ‘shortbevel’points. Injection of 15 ml of local analgesicsolution is made immediately below the ligamentand a further 5 ml is injected as the needle is withdrawnto just above the ligament. During finalwithdrawal of the needle the skin is pressed downwardsto prevent separation of the connective tissueand aspiration of air through the needle.It is important to ensure that the needles shallbe vertical when contact is first made with the cranialborder of the transverse processes for, if theyare not, redirection over the edge of the processesmay cause their points to lie well away from thecourse of the nerves. Successful infiltration aroundthe nerves is indicated first by the development ofa belt of hyperaemia which causes a distinct andappreciable rise in skin temperature. Full analgesiadevelops in about ten minutes and when lignocainewith adrenaline 1:400 000 is used it persistsfor about 90 minutes. When a unilateral block isfully developed it produces a curvature of the

324 ANAESTHESIA OF THE SPECIESFIG.12.6 Unilateral analgesia with either a paravertebralblock or lumbar epidural producing spinal curvaturetowards the affected side.spine, the convexity of which is towards the analgesicside (Fig. 12.6).An alternative method of lumbar paravertebralblock utilizing a lateral approach to the nerves isfavoured by some. About 10 ml of local analgesicsolution is injected beneath each transverseprocess towards the midline. The needle is thenwithdrawn a short distance and then redirectedfirst cranially, then caudally, with more analgesicsolution being injected along each line of insertion.A total of about 20 ml of solution is used for eachsite and the last portion of each 20 ml is injectedslightly dorsal and caudal to the transverseprocess to block dorsolateral branches of thenerves. With this technique analgesic solution maybe injected below fascial sheets and thus be preventedfrom bathing the nerves.It is inevitable that failure or at least partial failurewill sometimes attend attempts to inject localanalgesic solution in the immediate vicinity of aseries of nerves situated at a depth of 5–7 cm fromthe body surface, however careful the techniqueof injection and no matter which approach isadopted. Among the factors which reduce theprecision of the method are: the nerves traversethe intertransverse spaces obliquely; in some ani-17161218143213515467110915811 12FIG.12.7 Pudendal nerve block.Lateral view of the pelvis with the sacrosciatic ligament removed to show distribution ofthe sacral spinal nerves.1:Pudic nerve;2:middle haemorrhoidal nerve;3:caudal haemorrhoidal nerve;4,5:proximal anddistal cutaneous branches of pudic nerve;6:deep perineal nerve;7:nerve that becomes the dorsal nerve of the penis;8:sciatic nerve;9:branch connecting sciatic nerve with branch of pudic nerve 7;10:pelvic nerve;11:internal pudicartery;12:coccygeus muscle;13:external anal sphincter;14:sacrosciatic ligament;15:tuber ischii;16:sacrum;17:firstcoccygeal vertebra;18:needle in position.

CATTLE 325mals the nerve roots are double, emerging fromdouble foramina; it is difficult to ensure that thesite of injection is the same as that assessed fromthe body surface; penetration of the muscularmass of the back tends to cause spasmodic contractionof the muscles with consequent modificationof the needle track. Precise location of the injectionsites is also more difficult in the newer large breedsof cattle.Pudic (internal pudendal) blockWhile epidural block is a reliable means of provokingexposure of the penis in the bull, it must beacknowledged that the method also has disadvantages,particularly in heavier individuals. Thechief of these is that the volume of analgesic solutionrequired to cause complete exposure mayresult in severe interference with the motor powerof the hindlimbs, and in order to prevent injury tothe limbs and pelvis it becomes necessary to keepthe animal cast and restrained for several hours.But prolonged recumbency in a heavy bull, oftenassociated with struggling, may result in injuryelsewhere. A most useful alternative to produceanalgesia of the penis for examination and surgicalprocedures is a bilateral pudic (internal pudendal)block.The pudic (internal pudendal) nerve consists offibres arising from the ventral branches of the thirdand fourth sacral nerves. It passes ventrally andcaudally on the medial surface of the sacrosciaticligament, where it is associated with the middlehaemorrhoidal nerve, to cross the lesser sacrosciaticforamen where it is accompanied by theinternal pudic vessels; they then pass along thefloor of the pelvis to the ischial arch supplyingmotor fibres to the urethra and the erector andretractor muscles of the penis, the middle haemorrhoidalnerve and sensory fibres to the skin oneither side of the midline from the anus to the scrotum.Between the sacrosciatic ligament and the rectumin the region of surgical approach to the nervelies the sheet-like coccygeal muscle. The pudicnerve lies between the ligament and the muscle,while the accompanying middle haemorrhoidalnerve lies deep to the muscle, that is between it andthe rectal wall. The lesser sacrosciatic foramen isclosed by a sheet of fascia which is an extension ofthe fascia of the coccygeal muscle. In addition tothe pudic and middle haemorrhoidal nerves somefibres which enter into the dorsal nerve of the penisare obtained from a branch of the sciatic nervewhich, leaving the parent nerve on the outer aspectof the sacrosciatic ligament, passes into the lessersacrosciatic foramen and anastomoses with theventral branch of the pudic nerve where that liesimmediately above the internal pudic vessels closeto the ventral border of the foramen (Fig. 12.7).The pudic nerve is located per rectum, the handbeing introduced as far as the wrist and the fingersdirected laterally and ventrally to detect the lessersacrosciatic foramen. Its outline is not clearly identifiable,but its position is recognized by the softnessand depressability of the pelvic wall at thispoint. Moreover, the internal pudic artery whichcan readily be detected running along the lateroventralaspect of the pelvic cavity passes out ofthe pelvis at the cranial part of the foramen. Careshould be taken not to advance the hand too far,for on entering the rectum the foramen lies immediatelyventrolateral to the fingers. The nerve canreadily be felt, the size of a straw, lying on thesacrosciatic ligament immediately rostral and dorsalto the foramen.The site of insertion of the needle is at the pointof deepest depression of the ischiorectal fossa andit is directed rostral and slightly ventral in direction.During the whole procedure a hand is kept inthe rectum. When the needle has penetrated to adepth of 5–7 cm, it will be palpable through therectal wall and its point should be directed to theposition of the nerve a little rostral to the foramen.Here some 20–25 ml of 2% lignocaine hydrochloride(or its equivalent) is injected. Afurther 10–15mlis injected a little caudal and dorsal to this point toblock also the middle haemorrhoidal nerve whichmay carry some sympathetic fibres to the penis. Athird injection should be made after redirecting theneedle a little ventrally just inside the lesser sciaticforamen where the ventral branch of the pudicnerve can be palpated distal to its anastomosiswith sciatic nerve branches. The onset of adequateexposure of the penis is delayed for a period of30–45 min after injection of the nerves.Another approach to pudendal nerve block is alateral one. One injection is made over the pudendalnerve just as it passes medial to the dorsorostral

326 ANAESTHESIA OF THE SPECIESquadrant of the lesser sciatic foramen and a secondinjection is performed between the posterior haemorrhoidaland pudendal nerves. This latter injectionnecessitates penetration of the sacrosciaticligament. The site of insertion of the needle is determinedby using the cranial tuberosity of the tuberischii as a fixed point and the length of the sacrotuberousligament as a radius. The distance is usedto establish the site on a line drawn parallel to themidline anterior to the fixed point. After clipping,cleaning and disinfecting the skin the site ismarked by the s.c. injection of 2 ml of 2% lignocaineor equivalent drug solution. This injection makessubsequent manipulations less painful and rendersthe subject more amenable to handling. Eitherhand is then introduced into the rectum andthe lesser sciatic foramen located. A 12 cm long,1.8mm bore needle is introduced through the skinsite and directed towards the middle finger held inthe foramen until it can be felt to lie alongside thenerve. About 10 ml of the local analgesic solutionis injected at this point. The needle is withdrawn4–5 cm and redirected caudally and dorsally so thatit penetrates the sacrosciatic ligament at a pointabout 2.5 cm above and behind the first site of injection.About 5 ml of solution is injected at this point,the needle is withdrawn and the sites massaged tospread the solution in the tissues. Similar injectionsare carried out on the other side of the animal.Local analgesia for castrationFor castration the site of the proposed incision inthe scrotum may be desensitized by the s.c. infiltrationof local analgesic solution but this does not, ofcourse, block the nerve fibres running in the spermaticcord. These fibres can be blocked by thedirect injection of 5–10 ml of local analgesic solutioninto each cord at the neck of the scrotum or byinjecting 5–25 ml (depending on the size of the animal)into the substance of each testicle. In the lattermethod the drug is assumed to pass out fromthe testicle along the lymph vessels and to block,after diffusion, the nerve fibres present in the cord.The bulk of the drug is carried on in the lymph toenter the blood stream and for this reason excessivedosage must be avoided or intoxication will occur.For the closed or bloodless (Burdizzo) castrationthe skin of the neck of the scrotum must be infiltratedby s.c. injection and the spermatic cord itself isalso infiltrated at the same site. About 10–20 ml of2% lignocaine is a suitable dose on each side.Caudal epidural analgesiaThe spinal cord ends in the region of the last lumbarvertebra but the meningeal sac is continued asfar as the junction of the 3rd and 4th sacral segments.The diameter of the neural canal as it passesthrough the sacrum is approximately 1.8 cm in thecaudal part and 2 cm in the cranial. In the lumbarregions the dimensions of the canal are muchgreater, its width at the last segment being 4 cm.This helps to explain why paralysis of the spinalnerves as far forward as the first sacral is effectedwith comparatively small quantities of local analgesicsolution (20 ml), whereas paralysis of the craniallumbar nerves necessitates the injection ofmuch larger quantities (100 ml).Caudal epidural block is performed by insertionof the needle between the 1st and 2nd coccygealvertebrae, i.e. beyond the termination of thespinal cord and its meninges (Fig. 12.8). This site islarger and more easily penetrated and, in someanimals, more easily located than the sacrococcygealspace. One or more of the following methodsmay be used:1. The tail is gripped about 15 cm from its baseand raised ‘pump-handle’ fashion. The firstobvious articulation behind the sacrum is the firstintercoccygeal space.FIG.12.8 Caudal epidural injection made into the firstintercoccygeal space.

CATTLE 3272. Standing on one side of the animal andobserving the line of the croup, the prominence ofthe sacrum is seen. Moving the eye back towardsthe tail, the next prominence to be observed is thespine of the first coccygeal bone. The site is thedepression immediately behind it.3. The caudal prominence of the tuberosity ofthe ischium is palpated and the point selected10–11 cm in front of it. A line drawn directly overthe back from this point passes, in a medium-sizedanimal, through the depression between the firstand second coccygeal spines.The dimensions of the opening in the dorsal wallof the neural canal are approximately 2 cm transversely,2.5 cm craniocaudally and about 0.5 cm indepth.The canal is occupied by six caudal nerves,together with a vein on each side. The aperturebetween the two vertebral arches is closed by theinterarcual ligament and the space between thespines occupied by connective tissue. Surmountingthe spines is a variable amount of fat coveredby skin. The floor comprises, about the centre ofthe space, the intervertebral cartilaginous discand, in front and behind this, the surface of thevertebral centrum.An insensitive skin weal is made with the objectof preventing movement during insertion of theinjection needle and thus ensuring that the latter isintroduced in the correct position and direction.For insertion of the epidural needle the tail isallowed to hang naturally. The point of the needleis applied to the centre of the depression betweenthe 1st and 2nd coccygeal spines, taking care that itis precisely in the midline. The needle is advancedventrally and cranially at an angle of 15 ° with thevertical, until its point impinges on the floor of thecanal. Often, contact with a caudal nerve causesthe animal to move suddenly, and the anaesthetistshould be prepared for this.Provided the needle has been correctly introducedthere is usually no doubt but that it hasentered the epidural space. Sometimes, however,the point of the needle will tranverse the space andpenetrate the intervertebral disc. This is detected,on attaching the syringe and attempting to injectsolution, by a great resistance offered to thesyringe plunger. Should this error occur, the needleshould be slightly withdrawn, the syringe reappliedand injection attempted. When the pointof the needle is correctly placed in the neural canalthere is, for all practicable purposes, no resistanceand injection can be made quite easily. Sometimesblood issues from the needle due to penetration ofa vein but experience indicates that injection canstill be injected without harm. If thought preferablethe needle can be withdrawn, cleansed ofblood clot and reintroduced.The rate of injection should be rather slow, avolume of 15 ml being given over 10–15 seconds;2% lignocaine hydrochloride is now almost universallyused but the duration of block can, ifneeded be increased by using 0.5% bupivacaine.Production of caudal block means that motorcontrol of the hindlimbs is uninfluenced. When 2%solutions of lignocaine are used the total dose liesbetween 5 and 10 ml depending on the size of theanimal. Provided that the concentration of thesolution used is sufficient to paralyse the sensoryfibres, skin analgesia will develop in the tail andcroup as far as the mid-sacral region, the anus,vulva and perineum and the posterior aspect ofthe thighs. Paralysis of motor fibres will cause theanal sphincter to relax and the posterior part of therectum to balloon. Defaecation will be suspended,stretching of the vulva will produce no responseand the vagina will dilate. During parturitionstraining ceases but uterine contractions are uninfluenced.The onset of muscular paralysis of the tailoccurs from 60–90s after injection and affords reliableevidence that the injection has been made correctly.When lignocaine is used analgesia attains itsmaximum extent over 5–10 min, and persists forabout an hour after which there is progressiverecovery. The block completely disappears by theend of the second hour from the time of injection.The introduction of caudal epidural analgesiawas immediately followed by its use as a means ofcausing relaxation and exposure of the penis inbulls. For this, a minimum dose should be given,the epidural needle left in place and if extrusion ofthe penis does not occur after the elapse of anappropriate length of time additional small dosescan be given until it does. The dose necessary forpenile extrusion is very close to that causing somedegree of motor incoordination of the hind limbs.

328 ANAESTHESIA OF THE SPECIESAs yet, there is no way of determining the effectivedose in relation to weight or other measurementsand it is necessary to wait for at least 25 min beforeconcluding that the dose administered was inadequate.For this particular purpose caudal blockhas, nowadays, been replaced to a large extent bypudic nerve block, sympathetic blockade or by theuse of tranquillizers such as acepromazine, or theα 2 adrenoceptor agonists.Many other drugs are now commonly administeredinto the epidural space at the caudal site.Xylazine, 0.05 mg/kg diluted to 5 ml in 0.9% saline,is used to provide analgesia of the perineum and toreduce straining during parturition. Xylazine willinduce bilateral analgesia of dermatomes suppliedby the caudal, caudal rectal, perineal, pudendal,and caudal cutaneous femoral nerves (StJean et al.,1990). Analgesia develops by 20 min after administrationand persists for 2h. The tail will be flaccidand mild ataxia may be present. Sufficient xylazineis absorbed to induce mild sedation, decreasedruminal motility (bloat), bradycardia anddecreased MAP. These side effects may have a significantlyadverse effect in sick animals. A slightlyhigher dose of xylazine, 0.07 mg/kg in 7.5 ml of0.9% saline, has been used by caudal epidural injectionto provide analgesia for castration in maturebulls (Caulkett et al., 1993). Sedation was evident inthese animals and moderate ataxia, with recumbency,was observed in 14%. Surgery was performed30 minutes after injection and surgicalanalgesia was judged to be good in 81% of animalsbut pain or discomfort during emasculation wasapparent in the remaining bulls.Medetomidine, 0.015 mg/kg diluted with 0.9%saline to a volume of 5 ml, has been evaluated forepidural analgesia in cows (Lin et al., 1998). Resultsof this investigation showed that medetomidineinduced analgesia within 10 minutes and lasted412 ± 156 min (mean ± SD) – significantly longerthan lignocaine, 0.2 mg/kg, which lasted 10 to115 min (mean 43 ± 37 min). Systemic effects ofabsorbed medetomidine included mild to moderatesedation and mild ataxia.Lumbosacral epidural analgesiaInjection of local analgesic solutions in the caudalregion affords a method of inducing epidural analgesia,but when lumbar epidural block is requiredit is not always possible to produce satisfactorycranial spread from the caudal injection site.Consequently, some make the injection at the lumbosacralforamen although needles introducedhere may enter the subarachnoid space and oncethis has been done it is no longer really safe to proceedwith the induction of an epidural block untilthe puncture in the dural has become sealed. Thepatency of the hole in the dura persists for severalhours and if an immediate spinal block is essential,a deliberate, controlled subarachnoid block mustbe performed. However, a subarachnoid block canonly be managed in relatively small animals,where full use can be made of gravity to controlthe extent of neural blockade, so injection at thelumbosacral foramen is normally only employedin sheep, goats, small pigs and dogs.Injection into the epidural space in the lumbarregion can be employed to produce analgesia of anumber of body segments in cattle. By careful controlof the dose of local analgesic injected it is possibleto produce a belt of analgesia around theanimal’s trunk without interfering with control ofthe hind limbs. Although not easy to perform, inexpert hands it can be most effective.With the animal standing, the site for insertionof the needle is just to the right of the lumbar spinousprocess on a line 1.5 cm behind the cranialedge of the 2nd lumbar transverse process. An initialskin weal is produced using a fine needle and alongitudinal skin incision some 2–3 cm is made tofacilitate penetration by the spinal needle. Thespinal needle (14 gauge, 12 cm long) is directedventrally and medially at an angle of 10–13 ° withthe vertical for a distance of 7.5 cm – at which pointthe needle enters the neural canal. Even whensmall quantities of local analgesic are injectedalong the track of the needle, penetration of theinterarcual ligament is apparently painful andthus the animal needs adequate restraint. Theintervertebral space through which the needlemust pass to enter the epidural space is actually aninterosseous canal formed by the bases of thespinous processes cranially and caudally and bythe intervertebral articular processes laterally.Immediately the needle is felt to penetrate theinterarcual ligament the stilette is withdrawn andif air is heard to enter the needle it is certain that

CATTLE 329the epidural space has been entered. Alternatively,in the absence of air aspiration and if no fluid flowsfrom the needle, a trial injection is made. If theneedle is correctly placed in the epidural spacescarcely any pressure on the syringe plunger isneeded. If on removing the stilette, cerebrospinalfluid flows from the needle, the latter must bequickly but gently withdrawn until the flow ceasesand then injection made (Fig. 12.9).The cardiovascular response to segmental block(T13–L1) is associated with a reduction in MAP,and an increase in CO due to an increase in HR inresponse to decreased vascular resistance. Thesechanges appear to be of no clinical significance andit seems generally agreed that the sympatheticblockade caused by segmental epidural injection iswell tolerated by non-sedated healthy cows.Digital nerve blocksThe nerve supply of the digits of cattle is morecomplex than in the horse and regional analgesia ismore difficult to produce. The skin below the carpusand tarsus is tense and the subcutaneous tissuefibrous, so that precise location of the nerves isnot easy.Analgesia may be produced in the forelimb byinjection at the sites indicated in Fig. 12.10. TheABBFIG.12.9 Segmental epidural block.A First four lumbar vertebrae viewed from above.1:Point of insertion of spinalneedle through skin;2:articular process;3:transverse process;4:spinous processes.BTransverse section through thejoints between the articular processes of the 1st and 2nd lumbar vertebrae.The body of the 1st lumbar segmentis viewed from its caudal aspect.1:Needle in position;2:spinal cord surrounded by meninges;3:left 1st lumbarnerve;4:body of 1st lumbar vertebra;5:spinous process;6:transverse process;7:sectioned interlocking articularprocesses.FIG.12.10 Nerve block of the forelimb.To block the whole digit,injections must be made at A,B,C,D and E. To blockthe medial digit,inject at A,D and E. To block the lateral digit,inject at points B,C,D and E.

330 ANAESTHESIA OF THE SPECIESdorsal metacarpal nerve is located by palpation atabout the middle of the metacarpus, medial to theextensor tendon. The dorsal branch of the ulnarnerve is blocked about 5 cm above the fetlock onthe lateral aspect of the limb, in the groovebetween the suspensory ligament and themetacarpal bone. At this point, the palmar branchof the ulnar nerve may also be blocked, the twonerves being respectively situated in front of, andbehind the suspensory ligament. The axial palmaraspect of the digits may be rendered analgesic byan injection in the midline just above the fetlock.The injection will reach the lateral branch of themedian nerve before it divides, or if it has alreadydivided its two branches will still be close to eachother. The two branches may also be simultaneouslyblocked on the midline just below the levelof the dew claws, i.e. after they have passed frombelow the fibrous plate of the dew claws. Themedial branch of the median nerve is blocked onthe medial side of the limb in the groove betweenthe suspensory ligament and the flexor tendonsabout 5 cm above the fetlock. Blocking the mediannerve higher up the limb before it divides is notpractical as at this point the nerve lies beneath theartery and vein.An alternative technique that is less precise is toperform a ring block of the limb with local anaestheticsolution in an attempt to block all nervebranches at the same level.The hindlimb can be blocked to provide loss ofsensation below the hock. The peroneal nerve isblocked immediately behind the caudal edge ofthe lateral condyle of the tibia, over the fibula. Thenerve is blocked before it dips down between theextensor pedis and flexor metatarsi muscles todivide into the deep and superficial peroneal nerves.The bony prominence can easily be palpatedin most animals, and in some, the nerve itself canbe rolled against the bone as it passes superficially,obliquely downwards and cranially, at this point.An 18 or 20 gauge, 2.5 cm, needle is insertedthrough the skin, the subcutaneous tissue and theaponeurotic sheet of the biceps femoris until itspoint just touches the bony landmark. Lignocaine,approximately 20 ml of 2% for an adult, is injectedat this point. Onset of analgesia is in 20 minutes.The tibial nerve is blocked about 10–12 cmabove the summit of the calcaneous on the medialaspect of the limb, just in front of the gastrocnemiustendon. The gastrocnemius tendon isgrasped between the thumb and index finger ofone hand while a needle, about 2.5 cm long, isinserted immediately below the thumb until itspoint can be felt just under the skin by the indexfinger. About 15 ml of local analgesia solution isinjected at this site. A further 5 ml of solutionshould be injected on the medial side of the legto block a small cutaneous nerve. The block takes15 minutes to develop.An alternative method for desensitization ofthe hindlimb below the fetlock involves blockingthe superficial and deep peroneal nerves separately.The superficial peroneal nerve is blocked inthe upper third of the metatarsus where it liessubcutaneously over the midline of the dorsalaspect of the metatarsal bone (Fig. 12.11). The deepperoneal nerve accompanies the dorsal metatarsalvessels in a groove on the cranial aspect of themetatarsal bone under cover of the extensor tendons.Injection is made halfway between the hockand the fetlock. The needle is inserted from the lateralaspect of the bone and the point directedbeneath the edge of the tendon.The plantar metatarsal nerves are blocked onthe medial and lateral sides of the limb in thedepression between the suspensory ligament andFIG.12.11 Nerve block of the distal part of thehindlimb. A:injection of the superficial peroneal nerve.B:injection of the deep peroneal nerve.C:injection of theplantar metatarsal nerves.

CATTLE 331the flexor tendons, about 5 cm proximal to the fetlockjoint and deep to the superficial fascia (Fig.12.11). Five ml of local analgesia solution is injectedover each nerve.INTRAVENOUS REGIONALANALGESIAIntravenous regional analgesia (IVRA) is a simpleand commonly used technique to provide analgesiaof the limb or digits. It is achieved by injectinglocal analgesic solution into a superficialvein in a limb isolated from the general circulationby a tourniquet. The limb distal to the site of applicationof the tourniquet becomes analgesic andremains so until the tourniquet is released.The animal is restrained in lateral recumbency,with or without sedation. The hair over a prominentvein on the relevant limb is clipped and theskin prepared for injection (Fig. 12.12 ). A tourniquetof stout rubber tubing or a wide flat rubberband is applied above the carpus or hock, or abovethe fetlock, to occlude arterial blood flow. The flattourniquet is preferable as it appears to cause theanimals less discomfort than rubber tubing; consequently,they are less likely to be restless. Whenthe tourniquet is to be placed on the hind limbabove the hock in an adult animal, rolls of bandageshould be placed either side of the limb beneaththe tourniquet in the depression between the tibiaand the gastrocnemius tendon to ensure occlusionof all blood vessels (Fig. 12.12 ). A 19 gauge needleor butterfly needle is inserted into a vein with itspoint towards the foot. If the limb is to be exsanguinatedby application of an Esmarch bandage,the vein may be difficult to locate after applicationof the bandage; the needle should be placedfirst and kept patent with heparin-saline solution.In adult cattle, 30 ml of 2% lignocaine (withoutadrenaline) is injected into the vein after firstaspirating blood to confirm location of the needlewithin the lumen of the vessel. Some veterinariansmay follow that injection with saline to encouragespread of the local anaesthetic through the limb.Analgesia distal to the tourniquet will develop in15–20 minutes and persist until the tourniquet isremoved. Provided that 10 minutes or more haveelapsed since the injection, no adverse effect fromthe local analgesic solution should be observedwhen the tourniquet is removed. Analgesia dissipatesvery rapidly in almost all animals.Occasionally, the foot is analgesic everywhereexcept for the skin between the digits. This can beblocked by injection of 5 ml of 2% lignocaine midlineon the dorsal aspect of the fetlock and a further5 ml of solution on the caudal aspect of thefetlock between the dew claws.The duration of analgesia is limited only by thetime it is considered safe to leave a tourniquet inplace. Intravenous regional analgesia is safe for upto at least 1.5 hours and this is long enough formost procedures done on the bovine foot.(1) (2)FIG.12.12 Easily recognized veins of the distal parts oflimbs that can be used in placing needles or cannulae forintravenous regional analgesia.(1) Medial view of the rightforeleg.A:radial vein;B:medial palmar digital vein.(2)Lateral view of the right hindleg.C:lateral branch of lateralsaphenous vein;D:lateral plantar vein;E:lateral plantardigital vein.GENERAL ANAESTHESIAClearly, choice of technique depends in large parton the circumstances surrounding the need forsedation or anaesthesia. For example, managementof a dairy cow for caesarian section is different frommanagement of a beef or feedlot heifer that has notbeen handled. Sedating a bull for a foot trim or

332 ANAESTHESIA OF THE SPECIESradiographs may be more difficult when done onthe farm than when performed in the clinic.Regurgitation during anaesthesia is a real hazardwith potential consequence of pulmonaryaspiration of ruminal fluid and material, asphyxia,pulmonary abscesses, or pneumonia. Food is customarilywithheld from cattle older than 3 monthsof age before elective anaesthesia for 36 (24–48)hours, water for 8–12 hours, to decrease the volumeof the rumen contents. This reduction in gastrointestinalvolume has an added benefit ofimproving oxygenation during recumbency.Animals less than 2 months of age are likely todevelop hypoglycaemia if food and milk are withheldfor several hours. One recommendation is toprevent the calves from eating solid food for severalhours and to withhold milk or milk replacer for30 to 60 minutes before anaesthesia.Choice of drugs may be influenced by currentlegislature concerning use of anaesthetic agents infood-producing animals. In this chapter informationon the pharmacological effects of variousagents and their combinations is given in orderthat informed decisions can be made about theiruse in all situations. Some of the anaesthetic agentsmentioned may be unsuitable in some countriesfor use in animals for subsequent slaughter becauseof presumed persistence of drug residues.TABLE 12.1 Drug combinations used in cattleanaesthesiaDrugs Dose CommentsThiopental 11mg/kg i.v. Premedicationdecreases doserateGuaiphenesin50–100mg/kg i.v. Dose rate5% + decreases > 600 kg+ bodyweight;Thiopental 3–4mg/kg premedicationdecreases doserateXylazine 0.1–0.2mg/kg/ i.m. 15–20 min+ or i.v.+ duration;Ketamine 2mg/kg i.v. prolong with 1 gketamine in 1 litre5% guaiphenesin at1.5–2.0 ml/kg/hXylazine Infuse 1–2ml/kg100 mg/litre of the mixture i.v.+Guaiphenesin50 g/litre+Ketamine1 g/litremedetomidine is usual prior to anaesthesia withketamine, except in young calves in which anaesthesiacan be induced with diazepam-ketamine.ANAESTHETIC TECHNIQUESAnaesthesia can be induced in the standing animalwith only one assistant holding the head duringinjection, or the cow or bull can be first cast withropes or strapped to a tilting table and anaesthetizedin standing or lateral position. There is aclinically obvious difference in response to anaestheticdrugs between Bos taurus breeds and breedscrossed with Bos indicus. Dairy breeds in particularare relatively tolerant of the effects of anaesthesia.Breeds such as the Beefmaster, Santa Gertrudis,and Brahman often require a much lower dose ofanaesthetic agents.Premedication is not essential prior to injectionof thiopental or thiopental-guaiphenesin. Administrationof acepromazine or xylazine will decreasethe dose rate of induction drug, alter the cardiovascularparameters, and slow recovery fromanaesthesia. Premedication with xylazine orIntravenous injectionUse of an indwelling catheter is preferable to avoidperivascular injection of irritant drugs, such asthiopental or guaiphenesin, and to facilitate supplementalinjections. A 14 gauge, 13cm long catheter issuitable for insertion in the jugular vein, although a10 gauge catheter is better for administration ofguaiphenesin solutions in bulls. The skin of bullsmay be 0.5–1.0 cm thick over the jugular vein andinsertion of the catheter is easier through a smallincision made with a scalpel blade through an intradermalbleb of local analgesic (usually lignocaine).Endotracheal intubationThere are a variety of techniques that can be usedto facilitate endotracheal intubation in adult cattle.In cattle up to about 300 kg, intubation can beaccomplished under direct vision of the larynx

CATTLE 333FIG.12.13 Intubation by palpation.using a laryngoscope with a blade suitable forintubating a large dog. The animal is supported insternal position, the head and neck extended, andthe laryngoscope positioned at the corner of theanimal’s mouth with the tip of the blade on thedorsum of the tongue. The trachea is intubatedwith an endotracheal tube of 11–18 or 20 mm internaldiameter (ID), with a technique similar to thatused in dogs. Care must be taken in smaller calvesnot to use the blade of the laryngoscope as a leverwith the incisor teeth acting as a fulcrum.In large bovine animals, a longer laryngoscopeblade will be needed to view the laryngeal opening.A stiff stomach tube or a 2 m metal rod with ablunted end is passed through the mouth and intothe trachea. The laryngoscope is withdrawn andthe endotracheal tube is fed over the tube or rodand into the trachea, whereupon the tube or rod isremoved. One problem is that the tube may catchon the epiglottis unless it is rotated at the appropriatemoment.Intubation by palpation is a technique commonlyemployed for cows and bulls. The mouth ofthe anaesthetized animal must be held opensecurely using a wedge-shaped gag insertedbetween the molar teeth or any other gag suitablefor ruminants. A 25 mm or 30 mm ID endotrachealtube is used for adult cattle. The anaesthetistgrasps the end of the endotracheal tube and insertsthe arm and tube into the cow’s mouth, taking careto remain midline so that the endotracheal tubecuff does not brush against the sharp edges ofthe molar teeth and tear (Fig. 12.13). The forefingeris used to depress the epiglottis and thefree hand is used to advance the endotrachealtube onto the epiglottis. The arm inside themouth is then advanced a further 5 cm and theforefinger and middle finger are used to spreadthe arytenoids and open the larynx. The freehand is used to advance the endotracheal tubeinto the larynx and trachea. If the endotrachealtube catches at the entrance of the larynx, the forefingershould be swept around the tube to freeit for insertion. The anaesthetist’s arm is removedand the endotracheal tube inserted its full length.The endotracheal tube cuff should be inflatedimmediately and the tube secured with gauzeto the speculum, the halter, or by lengths of gauzearound the head or horns. When there is insufficientroom for both the anaesthetist’s arm andthe endotracheal tube, a stomach tube or metalrod can be inserted in a manner just describedand then the endotracheal tube fed over the tubeor rod and into the trachea after removal of theanaesthetist’s arm.Endotracheal tubes may be passed ‘blind’ bythe anaesthetist gripping the larynx with one handand feeding the endotracheal tube into the larynxwith the other hand. This is not an easy techniquebut the success rate of this technique increaseswith practice.The lubricant applied to any endotracheal tubeused in ruminant animals should never contain alocal analgesic drug for if it does the mucous membraneof the trachea and larynx may remain desensitizedfor some time after the tube is withdrawn. Theprotective cough reflex will then be absent and foreignmaterial may be inhaled into the bronchial tree.INJECTABLE ANAESTHETIC AGENTSThiopentalThiopental may be used in adult cattle either aloneto provide full anaesthesia for operations of shortduration or to induce anaesthesia that is thenmaintained by inhalation agents. In the unpremedicatedanimal thiopental, 5% or 10% solution, isinjected rapidly into the jugular vein in a dose of11mg/kg estimated body weight; if xylazine premedicationhas been used a dose of 5–6 mg/kg isusually adequate. The animal sinks quietly to theground within 20–30 seconds of injection and there

334 ANAESTHESIA OF THE SPECIESis a brief period of apnoea. Apnoea seldom lasts formore than 15–20 seconds and artificial respirationis not required. Surgical anaesthesia of about10minutes is followed by recovery which is completewithin 45 minutes. Recovery is usually quietand free from excitement. The animal can bepropped up, and will maintain a position of sternalrecumbency, about 12–15 min after injection of thedrug. The period of surgical anaesthesia is brief butadequate for operations of very short duration orfor endotracheal intubation prior to maintenanceof anaesthesia with an inhalation agent.Apart from the usual risks of anaesthesia inruminant animals the method is safe in healthycattle. Overdosage may occur when there is a grosserror in estimation of body weight. Underdosageis more frequent and the animal may remainstanding, but excitement does not occur. Failure toinduce anaesthesia may be the result of the injectionbeing made too slowly or because of perivascularinjection. Additional thiopental may beinjected i.v. immediately to achieve anaesthesiaprovided that i.v. access can be guaranteed.Perivascular injection should be treated by infiltrationof the area with 1–2 mg/kg of 2% lignocaineand several hundred ml of 0.9% saline in anattempt to avoid tissue necrosis and abscesses.Thiopental should not be administered by thisrapid injection technique to sick animals or animalswith compromized cardiovascular function.Young calves up to 2.5 months of age are not goodsubjects for thiopental anaesthesia and the use ofeven small doses for induction of anaesthesia cannotbe recommended.Thiopental-guaiphenesinApproximately 80–100 mg/kg of 5% guaiphenesinon it own is needed to produce recumbency in cattle.If pain-producing procedures are to follow,a combination of guaiphenesin and thiopentalshould always be used (50 g of guaiphenesin to 2 gthiopental sodium). The mixture is run rapidly intoa catheterized vein (perivascular injection willcause tissue necrosis and sloughing) to produce thedesired effect; the prior use of xylazine greatlydiminishes the necessary quantity of the combinationnecessary. Administration of the mixtureresults in a decrease in respiratory tidal volume andABP, and an increase in respiratory and heart rates.The dose rate in unpremedicated cattle up to500 kg is approximately 2 ml/kg and this ratedecreases substantially on a mg/kg basis, with evenlarge bulls seldom requiring more than 1500 mlof the mixture for anaesthesia adequate for endotrachealintubation. Administration of xylazinepremedication greatly reduces the dose raterequired for anaesthesia.The drugs may also be administered separately,in which case, guaiphenesin is first infused i.v.at 50 mg/kg followed by a bolus injection of 3–4mg/kg of thiopental.MethohexitalBecause recovery after methohexital (methohexitone)is so much more rapid than it is after thiopental,it might appear to be the better of the twocompounds for use in cattle. However, the action ofmethohexitone is, for unknown reasons, rather unpredictableand the rapid i.v. injection of a computeddose cannot be recommended. Given to adultcows by slow i.v. injection, assessing the effects producedas injection proceeds, the agent has provedto be quite satisfactory although muscle tremorsoccur as unconsciousness supervenes. These muscletremors appear to have no clinical significance.Methohexital appears to produce better conditionsfor endotracheal intubation than are producedby thiopental. The jaw is more relaxed for agiven degree of unconsciousness and the laryngealand cough mechanisms appear to be less active.Recovery from methohexital anaesthesia issmooth and extremely rapid but occasionally it isaccompanied by a return of the muscle tremorsseen during induction of anaesthesia.Doses of 1 mg/kg by rapid i.v. injection are sufficientto enable endotracheal intubation to be carriedout in young calves and can be used forcastration of calves whose ages range from 6 weeksto 10 months.PentobarbitalToosey (1959) found that 1.9–3.8 mg/kg of i.v. pentobarbitalproduced sedation in adult animalswhich remained standing, but swaying, on theirfeet. Thirty years later, Valverde et al. (1989) con-

CATTLE 335firmed that 2 mg/kg i.v. produces reliable sedationin standing adult cattle. These doses produce moderatesedation for 30 min and mild sedation for afurther 30 min. Respiratory rate is significantlydecreased but no changes have been measured inarterial blood gases.Full general anaesthesia may be induced insmall bovine animals by the slow i.v. injection ofpentobarbital, taking some 4 min over the injection.Induction is quiet and the dose for the productionof light anaesthesia varies from 1.00 to1.45 g/50 kg. Surgical anaesthesia persists forabout 30 min and is followed by slow recovery takingup to 3 h before the animal can regain its feet.For the very young calf – animals up to 1 monthold – pentobarbital is quite unsuitable. In theseyoung animals unconsciousness lightens slowlyover more than 2 days and there is a grave dangerthat during this period the animal will succumbfrom pulmonary oedema, or that it may subsequentlydevelop pneumonia.KetamineKetamine alone will not cause seizures in cattle butthe quality of anaesthesia obtained by it is poor.Premedication with xylazine produces quiet,smooth induction of anaesthesia with good musclerelaxation and a smooth recovery from anaesthesia.In young calves, premedication with xylazinemay be substituted with diazepam or acepromazine,with or without butorphanol. The doserate of ketamine is usually higher in calves than inmature animals.Xylazine is given to adult cattle either i.m. at0.1–0.2 mg/kg or i.v. at 0.05–0.10 mg/kg to producedeep sedation, often with recumbency. Ketamine isthen given i.v. in doses of 2 mg/kg to induce anaesthesia.Often, endotracheal intubation can be performedsoon after the xylazine injection and beforeketamine is given and whenever possible thisshould be done, for ketamine appears to producecopious salivation or an inability to swallow thenormal saliva volume. The duration of anaesthesiais about 15 min.In smaller animals of about 200–350 kg bodyweight, xylazine, 0.1–0.2 mg/kg, is given intramuscularly5–8 min before ketamine at either 6mg/kg by intramuscular injection or 4 mg/kg byintravenous injection. In calves, xylazine, 0.1mg/kg, and ketamine, 10 mg/kg, can be givenintramuscularly at the same time, or ketamine maybe administered after a few minutes intravenouslyat 4–6 mg/kg. Intramuscular administration ofxylazine and ketamine will provide 25–30 min ofanaesthesia. Anaesthesia can be maintained afterany of these combinations by intermittent injectionsor infusion of guaiphensin-ketamine, 1 gramof ketamine in 1 litre of 5% guaiphenesin, or byinhalation agents.The combination of diazepam and ketaminewill produce less cardiovascular depressionin calves than xylazine and ketamine. Diazepam,0.2 mg/kg, and ketamine, 5 mg/kg, can be combinedand injected intravenously as a bolus or inincrements to achieve the desired effect. This combinationwill provide about 15 min of anaesthesia.Butorphanol, 0.1–0.2 mg/kg, can be included withthis combination to increase analgesia and musclerelaxation. Anaesthesia may be prolonged byintermittent injections of diazepam and ketamine,or by inhalation agents.Medetomidine, 0.02 mg/kg, and ketamine,0.5mg/kg, given together intravenously is a combinationthat has been described to produce deepsedation lasting 30 min in calves that couldbe combined with local analgesia for surgery(Raekallio et al., 1991). As might be expected,hypoxaemia developed in the calves in dorsalrecumbency. Administration of atipamezole,20–60µg/kg, produced a rapid smooth recovery. Itshould be noted that in another study of medetomidinesedation in calves, injection of antipamezole,200 µg/kg, to reverse sedation inducedtransient severe hypotension and even sinus arrest(Ranheim et al., 1998). Therefore, reversal agentsshould be given cautiously while monitoring thepatient closely. Relapse of sedation may occur90minutes later.Ketamine-guaiphenesinA similar technique to that for thiopental/guaiphenesinemploys a mixture of 1 g of ketaminemixed with 50 g of guaiphenesin, infused i.v. toeffect.Anaesthesia can also be induced and maintainedby i.v. infusion of xylazine, guaiphenesin

336 ANAESTHESIA OF THE SPECIESand ketamine. Xylazine, 100 mg and ketamine1000 mg are added to 1 litre of 5% guaiphenesinand the mixture infused i.v. at 1–2 ml/kg. Alternatively,after induction of anaesthesia withxylazine and ketamine anaesthesia can be -maintained by intermittent or continuous infusionof a mixture of guaiphenesin-ketamine (1000 mgketamine added to 1 litre of 5% guaiphenesin)at approximately 2 ml/kg /h – there is no needto add xylazine to the maintenance anaestheticcombination because in cattle the half life ofxylazine is longer than ketamine. When anaesthesiais prolonged supplementation with O 2 isadvisable.PropofolIt would seem because of rapid and completerecovery, irrespective of the duration of anaesthesia,that propofol should be the ideal agentfor general anaesthesia in cattle. However, thereare very few reports of its use in these animals,probably due to cost making its use impractical inadults. In calves inhalation anaesthesia is easilymanaged and much less expensive so that therehas been little incentive to use an expensive i.v.agent.Personal experience (LWH) has been that onei.v. injection of propofol (5–6 mg/kg) provides, innon-premedicated calves up to 3 months of age,perfectably acceptable general anaesthesia of4–9min duration, with a smooth, excitement-freeawakening. Further work to establish the dose–response to propofol alone, and after α 2 adrenoceptorsagonists is needed.Tiletamine-zolazepamThe combination of tiletamine-zolazepam,4mg/kg, and xylazine, 0.1 mg/kg, injected i.m. insequence produced anaesthesia within minutesin calves (Thurmon et al., 1989). Analgesia lastedon average 70 min and the calves were able to walkin 130 ± 18 min from the time of the last injection.When higher doses of xylazine were used inanother group of calves some became apnoeic.Although not measured in this study, clinical experiencehas been that calves anaesthetized with tiletamine-zolazepambecome hypoxic when placedin dorsal recumbency.INHALATION ANAESTHESIAMask induction with halothane or isofluraneis possible with little difficulty in calves up to2months of age. A small animal circle system canbe used to deliver O 2 and anaesthetic initiallythrough a well-fitting mask. The calf can beunpremedicated or sedated with a combinationof diazepam, 0.1 mg/kg, butorphanol, 0.05–0.10 mg/kg, and xylazine, 0.02 mg/kg. With thecalf standing the mask is applied with the O 2 flowingat 3–4 l/min, the vaporizer setting starts at zeroand is increased by 0.5% increments every fewbreaths. As its legs begin to relax the calf is allowedto subside to the ground and it is supported in sternalrecumbency. The trachea is intubated underdirect vision of the larynx using a laryngoscope.The mouth can be held open using lengths ofgauze looped around the upper and lower jawsand the tongue pulled to the opposite side of themouth to the laryngoscope. After intubation thecuff is inflated and the tube secured by tying gauzearound the tube and then around the back of thecalf’s head. Subsequently the calf can be positionedor lifted onto the operating table.HalothaneHalothane is a useful inhalation anaesthetic forcattle and is usually administered by low-flowmethods with a precision vaporizer and CO 2absorption. Endotracheal intubation is first accomplishedafter administration of xylazine orthiopental or ketamine, with or without guaiphenesin.Tracheal intubation is associated withincreased circulating catecholamine concentrations(Semrad et al., 1986) and premature ventricularcontractions may develop in some animalsafter intubation, particularly when anaesthesia isnot deep. The prevalence of arrhythmias decreasesover 15 minutes. Halothane induces a significantdecrease in ABP with increasing depth of anaesthesiabut ABP is usually high during halothaneanaesthesia in mature male cattle.IsofluraneIsoflurane is often chosen for anaesthesia of youngcalves. MAP may fall due to peripheral vasodilatation,mucous membrane colour and capillary refill

CATTLE 337time remaining good. Induction of anaesthesia isnormally as smooth as it is with halothane whilerecovery is said to be more rapid than afterhalothane, although this is scientifically unsubstantiated.Isoflurane anaesthesia is satisfactory inadult cattle.Sevoflurane and desfluraneThe safe use of sevoflurane and desflurane in cattlehas still to be established. Administration of anaesthesiawith sevoflurane is similar to halothane andisoflurane except that higher inspired concentrationsare required to overcome its lower potency.Desflurane anaesthesia is easily controlled and,although expensive, its use in a closed system mayprove to be commercially acceptable.Nitrous oxideN 2 O/O 2 mixtures are not often used in cattlebecause of the progressive movement of N 2 O intothe rumen and intestines which results in bloat.N 2 O is not sufficiently potent to induce or maintainanaesthesia when given on its own and it is,therefore, administered with another agent such ashalothane or isoflurane.NEUROMUSCULAR BLOCKING DRUGSThe fact that in cattle peripheral nerve blocks areeasily used to produce skeletal muscle relaxationmeans that neuromuscular blocking drugs are seldomnecessary in clinical anaesthesia. Such furthermuscle relaxation as may be needed is usually providedby the i.v. injection of guaiphenesin.In experimental studies pancuronium(0.1mg/kg) has been found to produce relaxationof some 30–40 min duration. As in horses, but incontrast to other species of animal, the facial musclesare more resistant to neuromuscular blockthan are the limb muscles. Monitoring of blockshould, therefore, be carried out by stimulation ofnerves to limb muscles.MONITORINGMonitoring the anaesthetized animal is discussedin Chapter 2 but there are some differences fromthe general descriptions that should be noted. Thebovine eye rotates with increasing depth of anaesthesiainto a ventral rather than rostroventral positionand only the sclera can be seen; it then rotatesback into a central position during deep anaesthesia.The pupil usually constricts to a horizontal slitbut some pupillary dilatation may occur after ketamineadministration. The presence of a palpebralreflex indicates that anaesthesia is light. Duringketamine anaesthesia increased muscle tone mayresult in a centrally placed eye and strong palpebralreflex.Respiratory rate may be rapid (20–40 breaths/min) and the depth shallow. Mature bulls andcows develop high PaCO 2 during inhalationanaesthesia and IPPV is often necessary to preventsevere hypercapnia, which manifests as tachycardia.A rate of 10 breaths/min and a tidal volume of10 ml/kg (5–6 l for an adult cow or bull) will usuallymaintain a PaCO 2 of around 5.3 kPa (40 mmHg).Spontaneously breathing calves usually seriouslyhypoventilate when supine and IPPV with tidalvolumes of 12–15 ml/kg, at rates of 12 breathspermin and an inspiratory pressure of 30 mmHgmay be necessary to keep the PaCO 2 at about5.3 kPa (40 mmHg). Oxygenation when anaesthesiais being maintained with i.v. agents canbe provided by endotracheal intubation and connectionto an anaesthetic system or a demandvalve for assisted or controlled ventilation.Insufflation of O 2 at 15l/min through a small boretube down an endotracheal tube may preventhypoxaemia.Mature bulls and cows usually maintain HRs of60–80 beats/min during anaesthesia. Bulls andadult cows develop hypertension during anaesthesiaand systolic pressures of >200 mmHg arenot uncommon. Values obtained by indirect methodsof measurement are often incorrect, but ABP iseasily and accurately measured by direct meansusing a 20 or 22 gauge catheter placed in the middleor caudal auricular artery (Fig 2.15) and connectedto a manometer or electrical transducer.Hypotension should be treated in the usual manner,namely, by decreasing the rate of anaestheticadministration, infusing balanced electrolyte solutionand infusion of either dopamine or dobutamine.For prolonged anaesthesia or major surgeryit is common practice to give 10 ml/kg/h of

338 ANAESTHESIA OF THE SPECIESbalanced electrolyte solution while calves less than3 months of age should be given 2–5 ml/kg/h of5% dextrose in water to prevent the developmentof hypoglycaemia.In calves ABP is similar to that in other smallruminant animals. The MAP should be >60 mmHgand values less than this warrant treatment.Premedication with acepromazine or xylazinemay contribute to low ABPs.POSITIONINGCorrect positioning and padding is important asradial nerve damage may develop in the undermostforelimb in cattle that have been lying inlateral recumbency for more than about 20 min.Padding (e.g. inflated tractor tyre inner tubes)should be inserted under the shoulder and forearm.Position of the limbs in cattle is the same as inanaesthetized horses, but the difference in theshoulders makes it difficult to pull the lower forelimbforward to the same extent. The upper limbsshould be elevated into a horizontal position andthe head should be positioned with a pad underthe poll so that the nose is lower than the crown,allowing saliva and any regurgitated material todrain from the pharynx. The horns should be protectedfrom breakage.RECOVERY FROM ANAESTHESIACattle should be moved into sternal recumbencyand propped up in this position as soon as anaesthesiais terminated to allow eructation for theexpulsion of ruminal gases which impair respiratoryfunction. The endotracheal tube should not beremoved until the animal is swallowing and voluntarilywithdraws its tongue into its mouth. Thismay not occur for some time after coughing andchewing movements return. O 2 administration byinsufflation down the endotracheal tube, orthrough a facemask, should be carried out wheneverpossible. In animals that have been intubated,the tube should be removed with the cuff still partiallyinflated. Cattle often remain sitting for sometime after consciousness has returned and theprocess of standing is much more deliberate than itis in horses. After sevoflurane anaesthesia recoveryto standing is rapid.Cattle may be allowed to eat and drink within afew hours of recovery to consciousness, the precisetime depending, to some extent, on the anaestheticagents administered. Calves are usually preventedfrom suckling for an hour and hypoglycaemiashould be ruled out if recovery is slow.REFERENCESBlaze, C.A., LeBlanc, P.H. and Robinson, N.E.(1988) Effect of withholding feed on ventilationand the incidence of regurgitation duringhalothane anesthesia of adult cattle. AmericanJournal of Veterinary Research 49: 2126–2129.Campbell, K.B., Klavano, P.A., Richardson, P. andAlexander, J.E. (1979) Hemodynamic effects ofxylazine in the calf. American Journal of VeterinaryResearch 40: 1777–1780.Caulkett, N.A., MacDonald, D.G., Janzen, E.D., Cribb,P.N. and Fretz, P.B. (1993) Xylazine hydrochlorideepidural analgesia: a method of providing sedationand analgesia to facilitate castration of maturebulls. Compendium for Continuing Education15: 1155–1159.Court, M.H., Dodman, N.H., Levine, H.D., Richey, M.T.,Lee, J.W. and Hustead, D.R. (1992) Pharmacokineticsand milk residues of butorphanol in dairy cowsafter single intravenous administration. Journal ofVeterinary Pharmacology and Therapeutics15: 28–35.DeMoor, A. and Desmet, P. (1971) Effect of Rompun onacid-base-equilibrium and arterial O 2 pressure incattle. Veterinary Medical Reviews 2: 163–169.Eichner, R.D., Prior, R.L. and Kvasnicka, W.G. (1979)Xylazine-induced hyperglycemia in beef cattle.American Journal of Veterinary Research 40: 127–129.Fayed, A.H., Abdalla, E.B., Anderson, R.R., Spencer, K.and Johnson, H.D. (1989) Effect of xylazine inheifers under thermoneutral or heat stressconditions. American Journal of VeterinaryResearch 50: 151–153.Hay, A. (1991) Needle penetration of the globe duringretrobulbar and peribulbar injections. Ophthalmology98: 1017–1024.Hopkins, T.J. (1972) The clinical pharmacology ofxylazine in cattle. Australian Veterinary Journal48: 109–112.Klein, L. and Fisher, N. (1988) Cardiopulmonary effectsof restraint in dorsal recumbency on awake cattle.American Journal of Veterinary Research 49: 1605–1608.LeBlanc, M.M., Hubbell, J.A.E. and Smith, H.C. (1984)The effects of xylazine hydrochloride on intrauterinepressure in the cow. Theriogenology 21: 681–690.Lewis, C.A., Constable, P.D., Huhn, J.C. and Morin, D.E.(1999) Sedation with xylazine and lumbosacralepidural administration of lidocaine and xylazine

CATTLE 339for umbilical surgery in calves. Journal of theAmericanVeterinary Medical Association214: 89–95.Lin, H.C., Trachte, E.A., DeGraves, F.J., Rodgerson, D.H.,Steiss, J.E. and Carson, R.L. (1998) Evaluation ofanalgesia induced by epidural administration ofmedetomidine to cows. American Journal of VeterinaryResearch 59: 162–167.McGuirk, S.M., Bednarski, R.M. and Clayton, M.K.(1990) Bradycardia in cattle deprived of food. Journalof the AmericanVeterinary Medical Association196: 894–896.Pascoe, P.J. (1986) Humaneness of anelectroimmobilization unit for cattle. American Journalof Veterinary Research 47: 2252–2256.Raekallio, M., Kivalo, M., Jalanka, H. and Vainio, O.(1991) Medetomidine/ketamine sedation in calvesand its reversal with atipamezole. Journal of VeterinaryAnaesthesia 18: 45–47.Ranheim, B., Soli, N.E., Ryeng, K.A., Arnemo, J.M.and Horsberg, T.E. (1998) Pharmacokinetics ofmedetomidine and atipamezole in dairy calves:an agonist-antagonist interaction. Journal ofVeterinary Pharmacology and Therapeutics21: 428–432.Raptopoulos, D. and Weaver, B.M. (1984) Observationsfollowing intravenous xylazine administration insteers. Veterinary Record 114: 567–569.Rumsey, T.S. and Bond, J. (1976) Cardiorespiratorypatterns, rectal temperature, serum electrolytes andpacked cell volume in beef cattle deprived of feed andwater. Journal of Animal Science 42: 1227–1238.Salonen, J.S., Vaha-Vahe, T., Vainio, O. and Vakkuri, O.(1989) Single-dose pharmacokinetics of detomidine inthe horse and cow. Journal of Veterinary Pharmacologyand Therapeutics 12: 65–72.Semrad, S.D., Trim, C.M. and Hardee, G.E. (1986)Hypertension in bulls and steers anesthetizedwith guaifenesin-thiobarbiturate-halothanecombination. American Journal of VeterinaryResearch 47: 1577–1582.StJean, G., Skarda, R.T., Muir, W.W. and Hoffsis, G.F.(1990) Caudal epidural analgesia induced by xylazineadministration in cows. American Journal of VeterinaryResearch 51: 1232–1236.Symonds, H.W. and Mallinson, C.B. (1978) The effect ofxylazine and xylazine followed by insulin on bloodglucose and insulin in the dairy cow. Veterinary Record102: 27–29.Thurmon, J.C., Nelson, D.R., Hartsfield, S.M. andRumore, C.A. (1978) Effects of xylazine hydrochlorideon urine in cattle. Australian Veterinary Journal54: 178–180.Thurmon, J.C., Lin, H.C., Benson, G.J., Tranquieli, W.J.and Olson, W.A. (1989) Combining telazal andxylazine for anesthesia in calves. Veterinary medicine84: 824–830.Toosey, M.B. (1959) The uses of concentratedpentobarbitone sodium solution in bovine practice.Veterinary Record 71: 24–27.Vainio, O. (1988) Detomidine (letter to the editor).Veterinary Record 123: 655.Valuesde, A., Doheny, T.J., Dyson, D. and Valliant, A.E.(1989) Evaluation of pentobarbital as a drug forstanding sedation in castle. Veterinary Surgery18: 235–238.Wagner, A.E., Muir, W.W. and Grospitch, B.J. (1990)Cardiopulmonary effects of position in consciouscattle. American Journal of Veterinary Research 51: 7–10.Wong, D.H.W. (1993) Regional anaesthesia forintraocular surgery. Canadian Journal of Anaesthesia40: 635–657.

Anaesthesia of sheep, goats13and other herbivoresINTRODUCTIONAnaesthetic management of sheep and goats isusually uncomplicated with the notable exceptionthat regurgitation with potentially fatal pulmonaryaspiration is always a risk of sedation orgeneral anaesthesia. Furthermore, intubation canbe technically difficult, particularly in large rams,because the animals’ narrow jaws leave little roomto view the larynx during insertion of the endotrachealtube. Two factors should be considered inselection of anaesthetic protocols for these ruminants.First, dose rates of some anaesthetic agentsdiffer from those in other species. Secondly,animals that are not used to being handled or isolatedmay not exhibit signs commonly associatedwith sickness or pain. These animals will have areduced requirement for anaesthesia and failure torecognize this may result in overdosage.This chapter describes techniques and drug combinationsthat can be used to anaesthetize sheep,goats, and llamas in a variety of clinical settings.Local analgesia is useful in these species and detailson the techniques are included. Some informationon methods of anaesthesia of deer, camels and elephantshas been provided at the end of the chapter.LOCAL ANALGESIALocal analgesia techniques are highly useful insheep and goat practice because equipmentinvolved is inexpensive, cardiovascular and respiratorydepression are less than produced by generalanaesthesia, and the risk of regurgitation andaspiration is decreased. The immediate post surgicalrecovery time may or may not be shorter thanafter general anaesthesia, depending on the agentsand techniques used. Local anaesthetic agents mayinduce toxic symptoms when used inappropriately,especially when an excessive volume of localanaesthetic is injected. Limiting the initial administrationof lignocaine to 6 mg/kg has been foundto be safe; administration of lignocaine in excess of10 mg/kg can result in sufficiently high blood levelsto cause cardiovascular depression and centralnervous system stimulation. This section will alsodiscuss techniques of local nerve blocks involvinguse of opioids or α 2 adrenoceptor agonists.APPLICATIONS OF LOCAL ANAESTHESIACornual nerve blocks for dehorningThe cornual branches of the lachrymal and infratrochlearnerves provide sensory innervation tothe horns. The cornual branch of the lachrymalnerve emerges from the orbit behind the root of thesupraorbital process. The nerve, covered by a thinfrontalis muscle, divides into several branches,two of which supply mainly the lateral and caudalparts of the horn. The main trunk of theinfratrochlear nerve emerges from the orbit dorsomediallyand divides into two branches, the dorsal341

342 ANAESTHESIA OF THE SPECIESmaximum of 6 mg/kg or about 2–3 ml per site foradult animals.Care must be taken with young goats not toexceed the toxic dose of Lignocaine or to inadvertentlyinject local anaesthetic intravenously.Alternative analgesic techniques for dehorninginclude administration of xylazine for sedation, orproduction of light general anaesthesia withdiazepam and ketamine, Saffan®, propofol, or aninhalant. It must be remembered that when inhalationanaesthesia is employed, the oxygen must beswitched off and the facemask removed beforeapplication of a hot iron.CastrationFIG.13.1 Nerve blocks for dehorning of goats.Thecornual branches of both the lachrymal and infratrochlearnerves must be blocked.Care must be taken in young kidsto ensure that attempts to block both nerves do not leadto injection of toxic quantities of local analgesic solution.or cornual branch and the medial or frontalbranch. The cornual branch soon divides, one divisioncoursing to the dorsal aspect of the base of thehorn and ramifying dorsally and dorsomedially.The other division passes to the medial aspect ofthe base of the horn and gives off branches to themedial and caudomedial parts of it. Both divisionsare covered in part by the orbicularis and in partby the frontalis muscle.The site for producing block of the cornualbranch of the lachrymal nerve is caudal to the rootof the supraorbital process (Fig. 13.1). The needleshould be inserted as close as possible to the caudalridge of the root of the supraorbital process to adepth of 1.0–1.5 cm in adult goats. The syringeplunger should be withdrawn before injection tocheck that the tip of the needle has not penetratedthe large blood vessel located at this site.The site for blocking the cornual branch of theinfratrochlear nerve is at the dorsomedial marginof the orbit (Fig. 13.1). In some animals the nerve ispalpable by applying thumbnail pressure andmoving the skin over this area. The needle shouldbe inserted as close as possible to the marginof the orbit and under the muscle to a depth ofabout 0.5 cm. Local analgesic solution such as 2%Lignocaine should be injected at each site, up to aIn the UK the Protection of Animals (Anaesthetics)Act specifies that castration of male sheep over3 months of age and of male goats over 2 months ofage must be carried out under local or generalanaesthesia. All of the methods described for cattleare applicable.Caudal blockInjection of 2 (1–4) ml of 2% lignocaine solutioninto the epidural canal through the sacrococcygealspace will provide caudal epidural analgesia forobstetrical procedures involving the vagina,vulva, and perineum. A smaller volume of localanaesthetic, 0.75 to 1.0 ml of 1% lignocaine, willprovide analgesia for the docking of lambs’ tails.Strict attention must be paid to aseptic techniqueto avoid complications and several minutes mustbe allowed for analgesia to develop.The wool must be clipped from over the sacrumand the base of the tail. The site for needle placementis located by moving the tail up and downand palpating the most cranial point of articulation.A 20 gauge hypodermic needle is insertedmidline approximately at a 45 ° angle to the curvatureof the rump so that the tip of the needle entersthe vertebral column and may even thread for afew mm cranially. Addition of xylazine, 0.05mg/kg,will prolong analgesia for up to 36 hours.Continuous caudal block can be employed toprovide relief of conditions of the vagina and rectumwhich provoke severe and continuous straining.Continuous block is facilitated by placement

SHEEP, GOATS & OTHER HERBIVORES 343TABLE 13.1 Epidural analgesia for flanklaparotomy in goats. A lower dose rate,such as1 ml/7 kg,is sufficient for analgesia of thehindlimbs or perineal surgeryFIG.13.2 Catheter emerging from tip of Tuohy needle.of an epidural catheter. Threading of the catheterinto the epidural space is performed using a Tuohyneedle, which has a curved end that directs thecatheter (Fig. 13.2). The needle is withdrawn afterthe catheter has been advanced 6–8 cm in theepidural space. Local analgesic solution is injectedthrough the catheter whenever the animal showssigns of returning sensation. Extreme care must betaken to secure the catheter in position and toensure sterile injections by protecting the freecatheter end – capped and wrapped in sterilegauze, for example.Digital nerve blockDigital nerves are easily blocked with lignocaine atthe sites described for cattle. (Chapter 12)Epidural blockEpidural block can be produced by injection oflocal anaesthetic solution into the epidural space atthe lumbosacral junction. Complete analgesia andparalysis can be induced in the hindlimbs andabdomen to allow surgery, depending on the volumeof local anaesthetic injected (Trim, 1989). Thedose rates for different drugs and their times foronset of action are listed in Table 13.1. The doserates listed are to produce analgesia for flanklaparotomy. The dose should be decreased if theanimal is old, obese, or pregnant. A lower dose oflignocaine, such as 1 ml/7 kg, is sufficient for perinealor hindlimb surgical procedures, and for caesariansection. The long duration of hindlimbparalysis from bupivacaine block for caesariansection interferes with nursing of the newborn,and for that reason lignocaine with adrenaline isusually preferred.The lumbosacral junction is easy to palpate inthin animals but recognition of landmarks will benecessary to identify the point of needle insertionTreatment Onset Duration Standing(min) (h) (h)Lignocaine 25 2 3.5–5.02% withadrenaline,1 ml / 5 kgBupivacaine 45 4–6 8–120.5% or 0.75%,1 ml / 4 kgin muscled or fat animals. Epidural block can beperformed with the goat or sheep standing or inlateral recumbency. An imaginary line between thecranial borders of the ilium crosses betweenthe spinous processes of the last lumbar vertebrae(Fig. 13.3). The caudal borders of the ilium, wherethe angle bends to parallel midline, are level withthe cranial edge of the sacrum. The point of needleinsertion is midline halfway between the spinousprocess of the seventh lumbar vertebra and thesacrum. If the spinous process of the last lumbarvertebra can be palpated, the next depression caudalto it is the lumbosacral space. This area must beclipped and the skin prepared with a surgicalscrub.A spinal needle should be used because it has astilette to prevent injection of a core of subcutaneoustissue into the epidural space. The notch onthe hub of the needle indicates the direction of thebevel. Thus the anaesthetist can ensure that injectionof local anaesthetic solution is towards thehead of the animal.When epidural nerve block is to be performedon the conscious animal, 1–3 ml 2% lignocaineshould be injected subcutaneously with a fine needleat the site intended for insertion of the spinalneedle. For lambs, kids, and pygmy goats, a22 gauge 3.7 cm spinal needle can be used. Foradult animals a sturdier needle, such as an 18 gauge6.25 cm spinal needle, is recommended. The needleshould be inserted midline perpendicular to thecurvature of the hindquarters and perpendicularto the midline sagittal plane of the animal, i.e. notnecessarily parallel or perpendicular to the floor ortable top (Fig. 13.4).

344 ANAESTHESIA OF THE SPECIESFIG.13.3 Black pen has been used to identify the landmarks used to locate the lumbosacral space in a goat. An imaginaryline between the cranial edge of the ilium crosses midline between the spinous processes of the last two lumbarvertebrae.The wings of the ilium angle obliquely towards midline and the sacrum (S).Considerable pressure may be needed to introducethe needle through the skin and supraspinousligament and it may be preferable to puncturethe skin first with a larger, sharp hypodermic needle.Once introduced, the spinal needle should beadvanced gently for two reasons. First, to be ableFIG.13.4 Direction of insertion of needle for lumbarepidural injection in sheep in lateral recumbency.to appreciate the resistance then penetration of theinterarcuate ligament which lies over the epiduralspace, described as a ‘pop’, and secondly, to controlintroduction of the tip of the needle into theepidural space so that movement of the needle canbe stopped immediately. Further introduction ofthe needle will penetrate the spinal cord andthe animal, if conscious, will jump and may dislodgethe position of the needle. If the tip of theneedle strikes bone and the needle does not appearto be deep enough to be in the epidural space, theneedle should be withdrawn until the tip is justunder the skin and redirected in a cranial direction.If unsuccessful, the procedure should be repeatedwith the needle advanced in a caudal direction.After correct placement of the needle, thestilette should be removed and placed on a sterilesurface. A 3 ml syringe containing 0.5 ml air shouldbe attached to the spinal needle and the plungerwithdrawn to test for aspiration of cerebrospinalfluid (CSF) or blood. Attempts at aspiration shouldreveal only a vacuum and aspiration of air meansthat the syringe is not tightly attached to the needle.When no cerebrospinal fluid or blood is aspirated,a test injection of a small amount of airshould be made. Injection should be easy whenthe needle is in the epidural space. After correct

SHEEP, GOATS & OTHER HERBIVORES 345placement of the needle, the 3 ml syringe should bedetached and the syringe containing the localanaesthetic solution attached. Injection of the drugshould be made over at least 30 seconds. Fasterinjections result in increased intracranial pressurewhich, if the animal is conscious, manifest asopisthotonus, nystagmus, and collapse. Afterinjection, the spinal needle should be withdrawn.If analgesia of one side or leg is required the animalshould be placed in lateral recumbency withthe side to be desensitized underneath. Whenbilateral analgesia is required, the animal shouldbe positioned either prone or supine so that thevertebral canal is horizontal. The goat or sheepshould not be allowed to ‘dog-sit’, otherwise analgesiawill not develop cranially.The spinal cord may project into the sacrum insheep and goats and penetration of the dura willresult in aspiration of CSF. Injection into the subarachnoidspace of the same volume of local anaestheticintended for epidural analgesia will result inthe block extending further cranially and respiratoryarrest. Usually, the volume for subarachnoidinjection is half the epidural dose. There is somerisk of local anaesthetic solution entering CSFthrough the puncture hole if the spinal needle ispartly withdrawn and redirected into the epiduralspace a few mm distant from the original insertion.If the entry of the needle into a venous sinus is notdetected by aspirating blood, intravenous injectionmay result in cardiovascular depression. Thelocal anaesthetic solution should be warmed whenthe epidural injection is to be made in the consciousanimal. Injection of a cold solution willstimulate receptors in the spinal cord and the animalwill jump, possibly dislodging the needle.Indwelling catheters can be inserted into theepidural space at the lumbosacral junction using a16 gauge Tuohy needle as described for caudalanalgesia.Placement of a venous catheter is a sensible precautionwhen epidural analgesia is to be used forsurgery. Epidural injection of local anaestheticsolution causes paralysis of the splanchnic nervesand results in a decrease in blood pressure.Hypotension may develop, especially in hypovolaemicanimals, such as for caesarian section, oranimals positioned in such a way as to promotepooling of blood in the hindlimbs. In theseanimals, treatment should include expansion ofblood volume with intravenous administration offluid and injection of ephedrine, 0.06 mg/kg, ormethoxamine, 5–10 mg. Animals with urethralobstruction being given epidural analgesia for perinealurethrostomy or cystotomy may alreadyhave a distended urinary bladder at risk ofrupture. Nonetheless, administration of fluidintravenously is important to restore blood volumeand cardiovascular function. One option is todecrease the size of the bladder by cystocentesis.Alternatively, fluid infusion can begin at the timeof epidural administration so that surgical relief ofdistension can be accomplished before a substantialincrease in urine production occurs.Approximately 50% of human patientsexperience visceral pain during caesarian sectionunder epidural block with bupivacaine anddescribe the pain as poorly localized, dull pain, oras a feeling of heaviness or squeezing (Alahuhta etal., 1990). Sheep or goats may respond by movementor vocalization to manipulation of visceraduring laparotomy under epidural analgesia withlignocaine or bupivacaine. The animals may bemade more comfortable by i.v. butorphanol,0.1mg/kg, diazepam, 0.05–0.10mg/kg, or xylazine,0.02 mg/kg. Disadvantages of adjunct drugadministration include respiratory depression,pharyngeal relaxation that may promote regurgitationand pulmonary aspiration, and depressionof the lambs or kids delivered by caesariansection.Sensory block may extend several dermatomescranial to the level of motor block. Limb movementis possible even when the animal is sufficientlyanalgesic for surgery. During recoveryfrom epidural block, the ability to move thehindlimbs may develop before analgesia is lost,although the ability to stand may not return untillong after analgesia is gone.Respiratory paralysis can occur if local anaestheticsolution travels cranially to the neck. Thiswill occur if a too large volume is injected, i.e. inaccuratecalculation of dose. In this event, generalanesthesia must be quickly induced, the tracheaintubated and IPPV applied until the animal isable to breathe again.During recovery from epidural block producedby local anaesthetic solutions, the animal should

346 ANAESTHESIA OF THE SPECIESbe allowed to recover quietly. It will be able tomaintain sternal recumbency but there is potentialfor injury to the hindlimbs if it makes uncoordinatedattempts to rise.Epidural morphineEpidural injection of morphine, 0.1 mg/kg used asa 1 mg/ml preservative-free solution, or 15 mg/mldiluted in saline to 0.15–0.20 ml/kg, at the lumbosacraljunction will produce analgesia withoutparalysis. This technique can be used to decreasethe requirement for general anaesthetic agents andto provide postoperative analgesia. Its beneficialeffects were documented by a study during whichit was noted that goats given epidural morphineafter stifle surgery vocalized less and were lesslikely to grind their teeth than goats that had not(Pablo, 1993). Epidural morphine also providespain relief for 6 hours after abdominal surgery(Hendrickson et al., 1996).Epidural xylazineXylazine, 0.05 mg/kg, diluted with saline to0.1 ml/kg may be used as an adjunct to generalanaesthesia for surgery. Systemic effects of sedationand decreased gastrointestinal motility mayaccompany epidural administration of xylazine inruminants. A higher dose of xylazine, 0.4 mg/kg,has been injected at the lumbosacral junction oframs to produce analgesia for surgery involvinglateral deviation of the penis (Aminkov &Hubenov 1995). Analgesia extended to T5–T6within 10 minutes and lasted for 120–140 minutes.Although sedation was judged to be poor,- heartrates decreased moderately, the ability to swallowwas decreased, and the rams urinated frequently,and these are all signs indicative of systemicabsorption. The rams were supine during the surgicalprocedure but changes in PaO 2 and PaCO 2were clinically insignificant. Hindlimb motorblock lasted an average of 224 minutes.Paravertebral nerve blockIn sheep and goats lumbar paravertebral nerveblock is carried out using techniques similar tothose employed in cattle. For operations carriedout through the flank the thirteenth thoracic andfirst three lumbar nerves are blocked. For each ofthese nerves up to 5 ml of 1 or 2% lignocaine isused, divided and injected above and below theintertransverse ligament, up to a maximum totaldose of 6 mg/kg lignocaine. Onset of analgesiamay be as fast as 5 minutes. Duration of analgesiais an hour, or longer when lignocaine with adrenalineis used.Inverted L blockFlank laparotomy can be performed usinglocal infiltration of lignocaine in an inverted Lpattern 2 to 3 cm cranial and dorsal to theintended skin incision site. Blebs of lignocainemust be injected subcutaneously and deep inthe abdominal muscle at approximately 1.5 cmintervals along the injection site. The maximumdose of lignocaine to be injected at one time is6 mg/kg and dilution of 2% solution to 1% solutionmay be necessary to provide sufficient volumefor injection. The duration of analgesia is about1.5hours.Intravenous regional analgesiaSurgery on the limbs can be performed using intravenousregional analgesia (Chapter 10). Insheep and goats the tourniquet or sphygmomanometercuff is usually placed on the forelimbabove the elbow (taking care not to pinch skin inthe axilla) and on the hindlimb above the hock(leaving sufficient length of the saphenous vein forinjection) (Fig. 13.5). A tourniquet must be sufficientlytight to block arterial flow without beingexcessively tight, and a sphygmomanometer cuffused as a tourniquet must be inflated to above thesystolic blood pressure. Injection of 4 mg/kg lignocainewithout adrenaline should be made slowlythrough a 25 gauge needle directed towards thefoot. Care must be taken to keep the needle immobilewithin the vein during injection. Blood shouldbe aspirated before injection to confirm needleplacement within the vein. Onset of action is in15–20 minutes. Analgesia will persist as long as thetourniquet is in place but sensation will rapidlyreturn after the tourniquet is removed. The tourniquetshould not be released within 10 minutes of

SHEEP, GOATS & OTHER HERBIVORES 347FIG.13.5 Intravenous regional analgesia in the hindlimb of a goat. A tourniquet is tied around the limb proximal to theintravenous injection of lignocaine.the initial injection to allow time for the lignocaineto diffuse into tissues. Thereafter, releasingthe tourniquet has no clinical effect on the animal.No long lasting effect has been noted in sheepor goats when the tourniquet has been in place for2 hours.Peroneal and tibial nerve blockAnalgesia of the hindlimb below the hock can beachieved by peroneal and tibial nerve blocks. Theperoneal nerve is blocked by injection of 5 ml 2%lignocaine where the nerve runs obliquely caudodorsallyto cranioventrally approximately2.5 cm below the lateral condyle of the tibia. Thenerve can often be palpated by using thumbnailpressure to move the skin and underlying tissues.Analgesia of the dorsum of the foot is obviousfrom the animal’s stance (Fig. 13.6).The tibial nerve is blocked by infiltration of 4 mlof 2% solution of lignocaine on the medial side ofthe leg at the hock between the flexor tendons andthe gastrocnemius tendon. A further 1 ml is injectedat a similar site on the lateral side of the limb toblock a small cutaneous nerve, a branch of thecommon peroneal nerve originating at the middleof the thigh. Onset of analgesia should be within15 minutes and is accompanied by straightening ofthe hock (Fig. 13.6).SEDATIONFIG.13.6 Peroneal and tibial nerve block producesanalgesia distal to the hock.The hock will straighten andthe goat will stand on the dorsum of the fetlock.

348 ANAESTHESIA OF THE SPECIESSEDATIONSEDATIVE AGENTS EMPLOYED IN SHEEPAND GOATSAcepromazineAcepromazine, 0.05–0.1 mg/kg, can be used toprovide mild tranquilisation in sheep and goats.α 2 Adrenoceptor agonists and antagonistsXylazine, detomidine, medetomidine, or romifidineprovide light to heavy sedation according tothe dose rate administered. Use of these agentsalone provides satisfactory sedation for restraintor they can be used for premedication prior toinduction of anaesthesia with other anaestheticagents. Dose rates for xylazine range from 0.02 to0.2 mg/kg, the largest dose producing profoundsedation for many hours. Animals that are youngor sick will only require a low dose to induce sedation.Variation in the analgesic effects of xylazinehas been noted in different breeds of sheep, forexample, analgesia after xylazine was less inWelsh mountain sheep than in Clun sheep (Leyet al., 1990). The average weight of the WelshMountain was 46 kg compared with 69 kg for theClun and the authors hypothesized that the differencemay have been the result of dosing accordingto body weight rather than body surface area.This group of sedatives induces marked physiologicalchanges. A comparison of i.v. xylazine,0.15mg/kg, detomidine, 0.03 mg/kg, medetomidine,0.01 mg/kg, and romifidine, 0.05 mg/kg, indicatedthat all caused a significant decrease inPaO 2 (hypoxaemia) for 45 minutes with no alterationin PaCO 2 , and that respiratory rate increased(Celly et al., 1997). These observations are in generalagreement with previously published investigations.The authors suggested that, since thehypoxaemia was not due to hypoventilation orchange in body position, a possible cause might bean increase in shunt fraction occurring from segmentalairway obstruction, areas of pulmonaryatelectasis, or opening of previously closed vascularconnections. Of further clinical interest, thehypoxaemia outlasted the duration of sedation.Further investigation has confirmed that in sheepxylazine causes severe pulmonary parenchymaldamage, including capillary endothelial damage,intra-alveolar haemorrhage, and interstitial oedema(Celly et al., 1999). Xylazine administration has occasionallybeen associated with the developmentof clinical signs of pulmonary oedema in sheep.Xylazine induces a short-lived decrease in heartrate and a mild decrease in mean arterial pressure(MAP). Detomidine, medetomidine and romifidineinduce significant bradycardia whereas detomidineand romifidine increase MAP (Celly et al.,1997). The impact of these cardiovascular changeswill depend on the dose rate of the agent, concurrentadministration of other anaesthetics, and thephysical status of the patient.The effects of xylazine can be reversed by intravenousadministration of yohimbine, 0.1 mg/kg,tolazoline, 2 mg/kg, or doxapram, 0.5 mg/kg.Atipamezole 25 to 50 µg/kg i.v. can also be used toantagonize the effects of this group of sedatives.Diazepam and midazolamIntravenous administration of these agents alonemay produce some sedation and ataxia in sheepand goats for 15–30 minutes, but the degree ofsedation is unpredictable in healthy animals.Midazolam, 0.2 mg/kg i.v. significantly decreasedthe response of sheep to a mechanical painful stimulusfor 20 minutes (Kyles et al., 1995). Increasingthe dose rate to 0.3 mg/kg extended the durationof antinociception but not the intensity. Administrationof flumazenil, 0.02 mg/kg, markedlyattenuated the sedation and analgesia induced bymidazolam but did not abolish it completely.Diazepam, 0.2 mg/kg, i.v. can be used to producemild sedation for transdermal tracheal wash.OpioidsA variety of opioids have been used in sheep andgoats to provide intraoperative and postoperativeanalgesia. Pethidine (meperidine) has been usedfor many years as an adjunct to anaesthesia insheep and goats. Butorphanol, 0.05–0.20 mg/kg,i.m. or i.v. is useful to increase sedation fromxylazine, acepromazine, or diazepam. Butorphanolhas a rapid onset of action and given 5–10minutes before diazepam and ketamine facilitatesa smooth and relaxed induction of anaesthesia.

SHEEP, GOATS & OTHER HERBIVORES 349The duration of effect appears to be 1 to 2 hours.Buprenorphine, 0.006–0.010 mg/kg, given intramuscularly30 minutes before induction of anaesthesia,appears to decrease the concentration ofinhalation agent required for anaesthesia. Buprenorphinecan be repeated in 4 hours for treatingpostoperative pain.Buprenorphine, 0.006 and 0.012 mg/kg i.v. inexperimental sheep produced analgesia from40minutes to 3.5 hours against a thermal stimulusbut no detectable relief from pressure-inducedpain (Waterman et al., 1991). This difference ineffect against different types of pain, which has notbeen observed with pethidine or fentanyl, may berelated to the fact that buprenorphine is a partialagonist at the µ opioid receptor. Buprenorphine,0.006 mg/kg, did not cause any significant changein pHa, PaCO 2 or PaO 2 .Etorphine and carfentanilThese opioids are used for immobilization of nondomesticanimals. A study comparing intramuscularlyadministered etorphine or carfentanil, 10, 20,and 40 µg/kg of body weight, in instrumentedgoats described similar effects for both drugs(Heard et al., 1996). The goats were rapidly immobilized,more quickly with carfentanil (≤ 5 minutes)than with etorphine (5–10 minutes) andetorphine always induced transient struggling.Immobilization was characterized by limb andneck hyperextension with occasional vocalizationand bruxation. The goats were partially recoveredby an hour after etorphine administration butwere unable to stand at 2 hours after carfentanil.Both drugs significantly increased blood pressureand decreased heart rates without changing cardiacoutputs. Arterial O 2 content was not decreasedand the goats did not regurgitate.GENERAL ANAESTHESIAPREPARATIONWithholding food from small ruminants beforeanaesthesia is not a universal practice. However,most anaesthetists prefer to withhold food for24hours and water for 6 to 12 hours before anaesthesiawhenever possible to decrease pressure ofthe rumen on the diaphragm and aid ventilation,to decrease the severity of bloat, and to decreasethe prevalence and volume of regurgitation.Lambs and kids should be prevented from sucklingfor 30 to 60 minutes before anaesthesia.When heavy sedation or general anaesthesia isto be administered to an unfasted ruminant, rapidsequenceinduction of anaesthesia and intubationof the trachea should be performed.It is doubtful if atropine has any value as a generalpremedicant in sheep and goats. The dosesnecessary to prevent salivation completely (0.2–0.8mg/kg) produce undesirable tachycardia and oculareffects, while smaller doses merely make thesaliva more viscid and hence more difficult to drainfrom the oropharynx. Bradycardia develops seldomduring anaesthesia but may be treated by i.v. atropine,0.02mg/kg, or glycopyrrolate, 0.005mg/kg.Premedication is not essential before generalanaesthesia in small ruminants, as excitement atinduction is uncommon. Administration of an opioid,such as butorphanol, 0.05–0.20 mg/kg, orbuprenorphine, 0.01mg/kg, i.m. or i.v., will improvemuscle relaxation and will provide essential analgesiafor orthopaedic procedures. Xylazine is animportant part of induction of anaesthesia with axylazine and ketamine combination. Diazepam isoften administered concurrently with ketamine atthe time of induction.ANAESTHETIC TECHNIQUESIntravenous injectionThe site of venepuncture in sheep and goatsdepends mainly on the assistance available andthe personal preference of the anaesthetist. Thecephalic vein in the forelimb (Fig.13.7) and thesaphenous vein in the hindlimb are easily viewedafter the wool or hair over them has been clipped.It should be noted that the cephalic vein is moreoblique on the limb than in the dog (Fig.13.8). Acatheter (18 gauge, 5 cm long) can be inserted intoeither vein, capped, flushed with heparinizedsaline, and secured to the leg with adhesive tape. Abutterfly needle (21 gauge or 19 gauge) can beused in the cephalic vein.Goats have relatively long, thin necks withobvious jugular veins so that jugular venepuncture

350 ANAESTHESIA OF THE SPECIESFIG.13.7 Restraint of sheep for injection into thecephalic vein.For jugular venepuncture the sheep issimilarly restrained in the sitting position but it is not easyto place the needle correctly in the vein with the sheep inthis position and hence the injection of irritant substancesinto the jugular vein of the sitting sheep is to be avoided.or catheterization may be carried out with the goatstanding, as described for horses. A 14 gauge 8 cmlong catheter is suitable for mature animals. Sheephave relatively short, thick necks and jugularcatheterization is less easy.The ear veins are easily observed after the hairis clipped, especially in goats, and can be used forintravenous injection.Endotracheal intubationAfter induction of anaesthesia, the sheep or goatshould be held in a sternal, head up position tominimize the likelihood of regurgitation until thetrachea is intubated and the endotracheal tube cuffinflated. If regurgitation occurs during the processof intubation, the animal should be turned intoFIG.13.8 The cephalic vein in a goat is short and obliqueacross the forearm (black pen has been used to identifythe location of the left cephalic vein in this animal).lateral recumbency and the head lowered to allowdrainage. Regurgitated rumen material should bequickly scooped out of the mouth before trachealintubation is attempted. When difficulty isencountered in intubating the trachea, turning theanimal into dorsal recumbency with its head offthe end of the table may facilitate the process byoverextending the head and neck. Note that thisposition will impair ventilation and may promoteregurgitation.Endotracheal intubation is best performedunder direct vision with the aid of a laryngoscope.Full extension of the head and neck is essential toplace the pharynx and trachea in a straight line(Fig. 13.9). Strips of gauze around the upper andlower jaws may be used to hold them open andkeep the assistant’s fingers out of the anaesthetist’sview. The assistant holds the tongue in a gauze

SHEEP, GOATS & OTHER HERBIVORES 351FIG.13.9 Intubation of the trachea is facilitated by extending the head and neck to form a straight line and use of alaryngoscope to view the laryngeal opening.sponge for better grip and draws it out of themouth. Endotracheal tubes with 11–12 mm internaldiameter are used for adult sheep and goats,and up to 16 mm for large breeds of sheep. A metalor plastic covered stilette inside the endotrachealtube may be used to stiffen it and provide morecontrol over the tip of the tube. The tip (last 2 cm)of the stilette should be bent down at a 30 degreeangle. The laryngoscope blade should be used todepress the dorsum of the tongue and the tip of theblade must be positioned at the base of the tonguein front of the epiglottis. Downward pressure onthe length of the blade will expose the laryngealentrance. Care must be taken to avoid damagingthe incisor teeth. The tip of the endotracheal tube isplaced on the epiglottis and used to flatten itagainst the tongue before the tube is advanced intothe larynx and trachea. Slight resistance may befelt as the tube passes by the vocal cords. A lengthof gauze is tied tightly around the tube behind theincisors and then secured around the back of thehead behind the ears, or around the bottom jaw.The cuff is inflated to produce an airtight seal withinthe trachea.Alternative methods of intubation includeinserting a half-metre blunt-ended, thin metal rodinto the trachea under direct vision, removing thelaryngoscope, then feeding the endotracheal tubeover the rod into the larynx and trachea, whereuponthe rod is withdrawn. The tube may have tobe rotated 360 ° as it enters the pharynx in order forthe tip to pass over the epiglottis and enter the larynx.Utilizing another method, some anaesthetistsare able to pass the endotracheal tube into the tracheablindly. The endotracheal tube (which musthave a good curvature to it) is introduced into themouth with one hand and the tip fed into thelarynx, which is gripped externally by the anaesthetist’sother hand.Tubes lubricated with an analgesic jelly mayalso be passed through the nostril. The ventralnasal meatus is relatively large in sheep and goatsand although tubes passed via the nostril must besmaller than those introduced through the mouthreasonably adequately sized ones can be used. Ifthe tube passed up the nostril cannot be introducedblindly through the larynx a laryngoscopeis used to view the tip of the tube in the pharynx.The tip of the tube is grasped with forceps andassisted into the laryngeal opening as the tube isadvanced through the nostril.INJECTABLE ANAESTHETIC AGENTSMajor surgery and prolonged diagnostic proceduresin sheep and goats are best performed under

352 ANAESTHESIA OF THE SPECIESinhalation anaesthesia, using injectable anaestheticagents only for induction and to facilitate endotrachealintubation. The greatest disadvantage touse of injectable anaesthetics for maintenance aswell as induction of anaesthesia is the high likelihoodof hypoxaemia developing. Further, with theexception of propofol, extending anaesthesia timebeyond 30 minutes with injectable agents is oftenaccompanied by prolongation of recovery. Use ofpreanaesthetic drugs whose actions can be antagonized,such as the α 2 agonist sedatives or opioids,may shorten recovery but they also contribute togreater respiratory depression and hypoxaemia.ThiopentalThiopental has been extensively used to induceanaesthesia in sheep and goats. Onset of anaesthesiais fast and the drug can be titrated to achievethe desired effect. The dose range to induce anaesthesiain the unpremedicated animal is wide, 7 to20 mg/kg, and the low or high dose does not seemto correlate with any particular patient characteristic,not age nor conformation nor degree of illhealth. To avoid overdosage, an initial bolus doseof 5–7 mg/kg of 2.5% thiopental should be injected.Within 30 seconds the degree of centralnervous system depression can be assessed andfurther small boluses of drug administered every20 seconds until the jaws are relaxed for endotrachealintubation. The duration of anaesthesia isshort, at 5 to 10 minutes, depending on the dose ofthiopental administered. Recovery is usuallysmooth. Preanaesthetic sedation decreases thedose rate proportionately to the degree ofsedation.MethohexitalIn both sheep and goats the intravenous injectionof 4 mg/kg of a 2.5% solution of methohexital producesanaesthesia of 5–7 minutes’ duration.Recovery to standing position is complete within10–14 minutes of the injection but the recovery isusually associated with violent jerking or convulsivemovements and excitement if the animalis disturbed by noise during this period. Recoveryexcitement may be prevented by premedicationwith diazepam or xylazine. Premedicationwill decrease the induction dose of methohexital to2 mg/kg.PentobarbitalMany years ago Phillipson and Barnett (1939)reported the experimental use of pentobarbital insheep. The approximate dose rate in adult sheep is30 mg/kg when given by slow intravenous injectionbut there is great variation in response to thedrug and anaesthesia time is short – about 15 minutes.In contrast to its effects in other species,detoxification of pentobarbital in sheep is rapid.The dose rate for pentobarbital in goats is similarto that in sheep with a variable but longer durationof anaesthesia.It is important to note that commercially availablesolutions of pentobarbital may containpropylene glycol and this causes haemolysisand haematuria in goats and sheep. Clinically,injectable anaesthetic agents other than pentobarbitalare now usually used for anaesthesia.KetamineKetamine can be used for anaesthesia in sheep andgoats without fear of causing convulsions. Musclerelaxation is poor, but may be improved by sedativessuch as diazepam or xylazine (Table 13.2).Ketamine alone or when given in low dose rateswith diazepam appears to produce a state of sedationin which there is profound analgesia with onlypartial depression of the swallowing and coughreflexes. Large dose rates have been used but alower dose is all that is needed to accomplish endotrachealintubation. A useful drug combination forinduction of anaesthesia is diazepam, 0.25 mg/kgi.v., and ketamine, 5mg/kg (4–6mg/kg) i.v., administeredat the same time. In many animals, half ofthis calculated dose is sufficient for endotrachealintubation. Better muscle relaxation is achievedwhen i.v. butorphanol, 0.05–0.10mg/kg, is administeredbefore the diazepam and ketamine. A differentopioid or a small dose of xylazine, 0.02–0.05mg/kg, can be given as an alternative to butorphanol.Acepromazine, 0.05 mg/kg, i.v. or i.m. canbe substituted for the diazepam but sufficient timeshould be allowed for onset of action before injectionof ketamine, 6 mg/kg.

SHEEP, GOATS & OTHER HERBIVORES 353TABLE 13.2 Injectable drug combinations forgeneral anaesthesia in goats and sheepDrugs Dosage (mg/kg) Duration CommentsDiazepam 0.2 to 0.3 mg/kg i.v. 10–15 min Can include+ + butorphanolKetamine 5.0 to 7.5 mg/kg i.v. 0.1 mg/kgXylazine 0.1 mg/kg i.m. 30 min Additional+ + xylazine canKetamine 6 mg/kg i.v.or be added if11 mg/kg i.m. depth ofanaesthesia notadequateThiopental 7 to 20 mg/kg i.v. 10 min Not < 3 monthsage.Dosagevaries:inject 5mg/kg i.v.initiallyand titrateadditional drug‘to effect’Xylazine 0.1 mg/kg i.m. 45–60 Higher+ + min xylazinetiletamine- 4 mg/kg i.v.dose mayzolazepamcause apnoeaPropofol About 4 mg/kg i.v. Short; Quality ofcan be anaesthesiamaintained improved byby incremental premedicationinjectionsor infusionThe combination of xylazine and ketamine is easyto use and produces a longer duration of anaesthesia.In goats, onset of anaesthesia is approximately5 minutes after i.m. xylazine, 0.1 mg/kg, and ketamine,11 mg/kg. If attempts at intubation inducechewing movements, an additional injection ofxylazine, 0.1 mg/kg, should induce completerelaxation. The duration of surgical anaesthesia is30–40 minutes. Alternatively, xylazine can beadministered i.m. 5 minutes before induction ofanaesthesia by i.v. ketamine, 2–4 mg/kg. The durationof anaesthesia is shorter after i.v. comparedwith i.m. administration. A disadvantage to the useof xylazine and ketamine is that MAP and cardiacoutput are decreased. This is particularly apparentwhen xylazine and ketamine are administered priorto halothane or isoflurane, when the combinedeffects often result in low arterial blood pressure.A combination of medetomidine, 0.02 mg/kg,and ketamine, 2 mg/kg, has been used to anaesthetizesheep and the effects reversed by injectionof atipamezole, 0.125 mg/kg (Laitinen, 1990;Tulamo et al., 1995). In one study, anaesthesia wascontinued by a further injection of medetomidine,0.01 mg/kg, and ketamine, 1 mg/kg, 25 minutesafter the first injection (Tulamo et al., 1995).Administration of atipamezole 45 minutes afterinduction of anaesthesia resulted in the sheepstanding on average 15 minutes later. With thisanaesthetic protocol hypoxaemia and moderatehypoventilation develop, and cardiac arrest atinduction has been reported (Tulamo et al., 1995).Endotracheal intubation and supplementationwith oxygen is advisable during anaesthesia.Tiletamine-zolazepamIntravenous administration of tiletamine-zolazepamproduces longer lasting anaesthesia thandiazepam-ketamine. Tiletamine-zolazepam maynot provide sufficient analgesia for laparotomyand an additional drug should be included for analgesia.In one report, i.v. butorphanol, 0.5 mg/kg,and tiletamine-zolazepam, 12 mg/kg i.v. resultedin 35 minutes of anaesthesia (25–50 minutes)(Howard et al., 1990). Mean arterial pressures andheart rates were sustained at acceptable values,and cardiac output decreased by an average of30%. Apnoea was present immediately after inductionfor up to 72 seconds followed by apneusticbreathing patterns and hypoxaemia was presentfor the first 10 minutes of anaesthesia. Mildhypoventilation persisted for longer than theanaesthesia time.The combination of i.v. tiletamine-zolazepam,6.6 mg/kg, with i.v. ketamine, 6.6 mg/kg, andxylazine, 0.11 mg/kg, resulted in a longer durationof anaesthesia, 83 ± 27 min (mean and standarddeviation), and a protracted recovery, mean4hours (Lin et al., 1994). Hypotension was present30 minutes after induction and persisted for theremainder of anaesthesia. Blood gas analyses werenot performed, however, it is probable that hypoxaemiadeveloped in these animals.SaffanAnaesthesia may be induced in healthy sheep andgoats by the intravenous injection of 3 mg/kg

354 ANAESTHESIA OF THE SPECIESSaffan and this is sufficient for intubation and asmooth transition to inhalation anaesthesia. WhenSaffan is to be used as sole agent in lambs and kidsfor disbudding, recommended intravenous doserates are 4–6 mg/kg.The effects of Saffan on the heart rate, arterialblood pressure (ABP) and respiratory rate aredose-dependent. Saffan at 2.2 mg/kg i.v. producesa short-lived decrease in heart rate and ABP withsome slowing of respiration. This dose may produceabout 10 minutes of surgical anaesthesia withrecovery to the standing position about 20 minutesafter injection. A dose of 4.4 mg/kg Saffan mayproduce a longer duration of decreased heart rateand ABP, and about 15 minutes of anaesthesia withcomplete recovery after a further 30 minutes.PropofolPropofol has a licence for clinical use in dogs andcats. Its chief advantage lies in its rapid detoxificationand elimination resulting in rapid recoveryfrom anaesthesia, even after multiple supplements.Propofol, 5–7 mg/kg i.v. in unpremedicatedsheep and goats will induce anaesthesia sufficientfor endotracheal intubation (Pablo et al., 1997).Apnoea is common but regurgitation should notbe a problem if food and water have been withheldbefore anaesthesia. Premedication with acepromazine,0.05 mg/kg, and papaveretum, 0.4 mg/kg,(Correia et al., 1996), or detomidine, 0.01 mg/kg,and butorphanol, 0.1 mg/kg (Carroll et al., 1998),all given i.m. decreased the dose of propofol forintubation to approximately 4 mg/kg.Anaesthesia can be maintained with an inhalantanaesthetic or maintained by continuousinfusion of propofol. The cardiopulmonary effectsduring anaesthesia maintained with halothane orisoflurane will reflect the influence of the inhalant.Recovery from anaesthesia is usually smooth andrapid.The infusion rate of propofol to maintain anaesthesiafor surgery is within the range 0.3 to0.6 mg/kg/min and depends on the presence orabsence of premedication and the intensity of thesurgical stimulus. The animals should be lessresponsive to the surgical stimulus when theyhave been premedicated with a sedative or a sedativeand opioid combination. Moderate to severehypoventilation occurs in sheep and goats duringcontinuous propofol anaesthesia, resulting inhypercapnia (Lin et al., 1997; Carroll et al., 1998).Consequently, endotracheal intubation and supplementationwith O 2 is recommended, either byinsufflation of O 2 at 50–100 ml/kg/min into theendotracheal tube or by giving 100% O 2 from ananaesthesia machine. MAP may be low afterinduction of anaesthesia with propofol but shouldprogressively rise with time. Recovery from anaesthesiais rapid with the animals standing 10 to 20minutes after propofol infusion is discontinued.Combination of propofol with ketamine is analternative technique for total intravenous anaesthesiathat has been tried in sheep (Correia et al.,1996). Induction was achieved with propofol,3mg/kg, and ketamine, 1 mg/kg. Anaesthesia wasmaintained for the first 20 minutes with a combinedinfusion of propofol, 0.3 mg/kg/min, withketamine, 0.2 mg/kg/min. This infusion rate wassubsequently decreased to 0.2 mg/kg/min ofpropofol and 0.1 mg/kg/min of ketamine. Recoveryfrom anaesthesia was rapid and free fromexcitement.Guaiphenesin (guaifenesin,glycerylguaiacolate,GGE)Maintenance of anaesthesia with an infusion ofguaiphenesin and ketamine after induction withxylazine and ketamine is a common protocol fortotal intravenous anaesthesia (TIVA) in cattle over200 kg body weight (see Chapter 12). Guaiphenesinis not often used in sheep and goats because ofits cost, but it can be used. One report describedanaesthesia of sheep with an infusion of guaiphenesin,50 mg/ml, ketamine, 1 mg/ml, and xylazine,0.1 mg/ml, combined in 5% dextrose in water.Anaesthesia was induced by rapid administrationof 1.2 ml/kg of the mixture and maintained byinfusion at 2.6 ml/kg/h (Lin et al., 1993). The sheepwere intubated and breathing air. Respiratoryrates were fast and the animals were severelyhypoxaemic with an average PaO 2 of 4.8 kPa(36.4 mmHg) at 30 minutes of anaesthesia. Heartrates and MAPs remained within acceptableranges of values. Recovery was smooth with timefrom termination of infusion to standing of 96 ± 50minutes. The advantage of the technique is the

SHEEP, GOATS & OTHER HERBIVORES 355constant level of anaesthesia that can be producedby a continuous infusion. Nonetheless, the severityof the decrease in PaO 2 introduces potential fora fatal outcome unless O 2 administration is includedin the technique.INHALATION ANAESTHESIAInhalation anaesthesia is a popular and reasonablysafe technique for providing anaesthesia forsurgery and medical diagnostic procedures.Halothane/O 2 and isoflurane/O 2 are the mostcommonly used inhalation anaesthetics in ruminants.They offer advantages over injectable agentsof easy control of the depth of anaesthesia, O 2 thatusually prevents hypoxaemia, and rapid recoveryfrom anaesthesia. The greatest disadvantages arethe production of respiratory and cardiovasculardepression that may require treatment with IPPVand vasoactive drugs.Tracheal intubation prior to halothane or isofluraneanaesthesia is usually accomplished afteranaesthesia is first induced with injectable agents.Induction of anaesthesia with the inhalant deliveredthrough a facemask is less desirable in anadult sheep or goat. The longer time for inductionallows accumulation of saliva in the pharynx andincreases the time before endotracheal intubation,during which regurgitation and aspiration canoccur. Induction with an inhalant also requires thatdeep anaesthesia is induced to facilitate endotrachealintubation, and this is often accompanied bya significant decrease in ABP. Furthermore, inductionusing a mask is often physically resented bythe adult animal. In contrast, young lambs andkids are easily induced with halothane or isofluranevia facemask.Anaesthetic breathing systems that are used fordogs can be used for sheep and goats. The initialvaporizer setting will depend on the anaestheticagents used for induction of anaesthesia and thetype of breathing system. For example, afterinduction and intubation in animals anaesthetizedwith acepromazine and thiopental, or butorphanol,diazepam and ketamine, and connectionto a circle circuit, a halothane vaporizer (vaporizerout of circle) may be set at 1.5% or the isofluranevaporizer at 2.0 or 2.5% with an oxygen flow rate of1 to 2 l/min. In contrast, after induction of anaesthesiawith xylazine and ketamine, or with tiletamine-zolazepam,the central nervous systemdepression is greater and the vaporizer settingshould be lower, for example, 0.50 to 0.75%halothane or 1% isoflurane. In either case, as thedepth of anaesthesia changes with time and onsetof surgery, the vaporizer setting can be adjusted upor down as needed. After about 20 minutes, whenthe blood anaesthetic concentrations are more stable,O 2 flow can be reduced to 1.0 or 0.5 l/min, ifdesired, to limit wastage of inhalant agent.Lambs and kids may be connected to a T-pieceor Bain circuit. The inspired anaesthetic concentrationis the same as the vaporizer setting and thusduring maintenance of anaesthesia should beabout 1.0 to 1.5 % for halothane or 1.4 to 1.8% forisoflurane, depending on the degree of preanaestheticsedation provided.Halothane,isoflurane,and sevofluraneAll these agents cause dose-dependent decreasesin ABP and cardiac output. MAC value forsevoflurane has been reported as 3.3% in sheepand 2.7% in goats (Clarke, 1999).Nitrous oxide (N 2 O)A major disadvantage of N 2 O is that it rapidly diffusesinto the rumen and causes bloat and respiratorycompromise. However, N 2 O can be used as anadjunct to injectable anaesthesia or used to supplementand decrease the requirement for halothaneor isoflurane. Low flows must not be used withN 2 O and a circle rebreathing system. Gas flows fora small sheep or goat should be 1 l/min each of O 2and N 2 O, with an increase to 2 l/min of each forvery large animals.ANAESTHETIC MANAGEMENTPositioningDuring anaesthesia, the head and neck should bepositioned so that the nose is lower than the pharynxfor drainage of saliva and any regurgitatedruminal fluid. Salivation will continue throughoutanaesthesia and saliva ceases to flow fromthe mouth only when it is accumulating in the

356 ANAESTHESIA OF THE SPECIESpharynx or because a deep plane of anaesthesiahas decreased production.Fluid therapyBalanced electrolyte solution, such as lactatedRinger’s solution at 10 ml/kg/h, should beinfused i.v. when surgery is being performed orwhen anaesthesia time becomes extended.Animals less than age 3 months should alsoreceive 5% dextrose in water at 2 to 5 ml/kg/h.Occasionally an adult ruminant develops hypoglycaemia,and this should be suspected any timethat recovery is more prolonged, or after recoveryfrom the immediate effects of the anaesthetic if theanimal is more lethargic than anticipated.MonitoringThe position of the eyeball during inhalationanaesthesia in goats and sheep is similar to the patternobserved in anaesthetized dogs; the eye rollsrostroventral between light and medium depthanaesthesia, and returns to a central position duringdeep plane of anaesthesia. Occasionally duringlight anaesthesia the eye will rotate dorsally (‘stargazing’). The palpebral reflex is lost in medium todeep anaesthesia. The pupil should be merely a slitduring an adequate plane of inhalation anaesthesiaand dilates in light or deep anaesthesia.The pupil dilates after ketamine administrationalthough, if the dose rate is low, the pupil mayclose down during inhalation anaesthesia.Respiratory rates are usually 15–30 breaths/minute; higher rates are associated with hypoventilationor hypoxaemia. Oxygen saturation andpulse rate can be monitored using a pulse oximeterwith a probe on the tongue. The depth of eachbreath is impaired when these animals are supineand moderate to severe hypercapnia usuallydevelops during inhalation anaesthesia. Oxygenationis usually adequate when the inspired gas isO 2 rich. Rumen bloat may develop during anaesthesiadespite preoperative fasting, pressing on thediaphragm and further impairing ventilation.Bloating can often be relieved by passage of a widebore tube through the mouth into the rumen, butthe tube may become blocked. Tachycardia, andsometimes hypertension, may develop as a consequenceof the hypercapnia and these will return tonormal values after the onset of controlled ventilation.Other potential consequences of hypoventilationare the lack of adequate anaesthesia duringinhalation anaesthesia despite a high vaporizersetting, and hepatic ischaemia as a result of hypercapnia-inducedsplanchnic vasoconstriction. Anear normal PaCO 2 results when IPPV is appliedat 12 breaths/min and an inspiratory pressure of20–25 cmH 2 O or tidal volume of 15 ml/kg.Peripheral arteries that are easily palpated orcan be used for indirect methods of blood pressuremeasurement are on the caudomedial side of theforelimb above or below the carpus and on thehindlimb on the dorsal surface of the metatarsus(Fig. 13.10). The median and caudal auriculararteries on the outside surface of the ear can beused for needle or catheter placement for directRight forelimb(palmar view)Cranial tibialarteryRadial arteryPalmarmetacarpalarteryRight hindlimb(cranial view)FIG.13.10 Schematic drawing of the arteries onfore- and hindlimbs for palpation of pulses and indirectblood pressure measurement.

SHEEP, GOATS & OTHER HERBIVORES 357measurement of arterial pressure and for collectionof blood for pH and blood gas analysis (seeChapter 2, Fig. 2.15). Heart rates are most frequentlybetween 60 and 120 beats/minute. Heart ratesless than 55 beats/min should be considered toconstitute bradycardia and heart rates greater than140 beats/min should be investigated for possibleabnormal cause. MAP should be above 70 mmHgduring anaesthesia.It is not uncommon for the animal’s temperatureto decrease to 37.2 ° C (99 ° F) before anaesthesiaafter 24 hours without food. Hypothermia maydevelop during anaesthesia and efforts should bemade to prevent heat loss. Sheep and goats requireexternal application of heat when rectal temperaturedecreases to 35.5 ° C (96 ° F) to avoid prolongedrecovery. Conversely, anaesthesia in a hotenvironment may result in hyperthermia.Treatment of hypotensionMean pressures below 65 mmHg should be treatedappropriately according to the suspected causeof hypotension. Treatment might include a 10 to20ml/kg bolus of electrolyte solution intravenouslyand lightening the depth of anaesthesia. Cardiovascularstimulation may be achieved by administrationof a catecholamine, such as an intravenousbolus of ephedrine, 0.03–0.06mg/kg, or an infusionof dopamine or dobutamine at 5–7 µg/kg/min of a100µg/ml solution in 0.9% saline. Blood loss can betreated initially by infusion of lactated Ringer’ssolution at 2 to 3 times the volume of blood lost andby decreasing anaesthetic administration.RecoveryThe animal should be placed prone at the end ofanaesthesia. When bloat is present ruminal gasshould be heard and smelled at the mouth.Regurgitation during anaesthesia is not a problemwhen the endotracheal tube is present and the cuffinflated to produce an airtight seal. Solid rumenmaterial should be removed from the pharynxbefore the end of anaesthesia. It must be rememberedthat regurgitation may occur when the animalis waking up. Consequently, the endotrachealtube must not be removed until the animal ischewing, swallowing, and can withdraw its tongueback into its mouth; this may be a considerabletime after the animal is able to lift up its head.Recovery is usually quiet and, unlike horses, ruminantsmay be in no hurry to stand after anaesthesia.Full control of swallowing and gastrointestinalmotility may not return for several hours afterxylazine administration and feeding must bedelayed. Hay or grass and water may be allowed3 hours after anaesthesia with most other agentsused in these species.Pain reliefThe relief of postoperative pain demands the samecare in goats and sheep as in all other animals.Signs of pain are not as obvious as in some otherspecies. Shivering may be a sign of anxiety. Immobility,vocalization, or grinding the teeth may beindicators that the animal is experiencing pain.Systemic administration of opioids may includei.m. 2 to 4 mg/kg of pethidine, 0.2 mg/kg of butorphanol,or 0.006 to 0.010 mg/kg of buprenorphine.Epidural injection of 0.1 mg/kg of morphine willprovide analgesia for procedures on the hindlimbsor abdomen.OTHER HERBIVORESLLAMAS (lama glama) AND ALPACAS(lama pacos)Llamas may weigh up to 200 kg and live up to20 years. Alpaca males weigh on average 60 kg.These animals should be handled with care asllamas can kick, swinging the limb forward andout, and males may bite. Use of side rails is notadvised, as a leg can be broken. Some commercialllama chutes incorporate straps which are passedunder the animal’s thorax and caudal abdomen toprevent the animal assuming sternal recumbency.Most llamas and alpacas tolerate a halter with arope lead. Suggestions for manual restraintinclude holding the haltered head and exerting thefull force of your weight on the hindlimbs to forcethe animal into a sternal recumbent submissiveposition (cush) (Jessup & Lance, 1982). This worksbecause the forelimbs are the main weight bearersand the hindlimbs cannot be locked up. Tapping

358 ANAESTHESIA OF THE SPECIESTABLE 13.3 Comparison of mean times foronset and duration of epidural analgesia with2% lignocaine,0.22 mg/kg,and diluted 10%xylazine,0.17 mg/kg,in six llamas (Grubb et al.,1993)Treatment Onset (min) Duration(min)Lignocaine 3 71Xylazine 21 187Lignocaine/xylazine 4 326A technique for castration in the standing llamahas been performed in more than 100 animalswithout complications (Barrington et al., 1993).Butorphanol, 0.1 mg/kg, i.m. was administered15minutes before applying a surgical scrub to theperineal region. Lignocaine, 2–5 ml of a 2% solution,was injected into each testicle until it becameturgid and a further 1–2ml was deposited subcutaneouslyat the site of the proposed incision as theneedle was withdrawn. The lower dose of lignocaineis recommended for llamas weighing lessthan 30 kg. These authors noted that llamas givenbutorphanol are not sedated but also that they donot exhibit the signs of discomfort and restlessnessduring the procedure that have been observed inanimals castrated with only local analgesia.behind the knee of the forelimb may help.Weanling or yearlings should not be tied as theymay struggle and injure cervical vertebrae.Aggressive handling or striking an animal willresult in fear, distrust and spitting.Caudal epidural analgesiaCaudal epidural injection of lignocaine, xylazine,or a combination of these has been evaluated in llamas(Grubb et al., 1993). Injections were made intothe sacrococcygeal space where the epidural spaceis shallow and easily entered. The procedure wasperformed with a 20 gauge, 2.5 cm long needleinserted at a 60 ° angle to the base of the tail. Onsetof action was rapid after injection of lignocaineand analgesia lasted longest when a combinationof lignocaine and xylazine was used (Table 13.3).Ataxia did not develop, although the llamas tendedto lie down. The dose rate of xylazine used inthis study was toward the high end of the doserange used in ruminants and from which somesystemic effects are to be expected. Mild sedationdeveloped in half the llamas given xylazine, beginningabout 20 minutes after injection and lastingfor 20–30 minutes. The synergistic effect on durationof analgesia caused by combining xylazinewith lignocaine is similar to that in horses.Local analgesia for castrationPreparation for anaesthesiaA number of publications are available documentingthe reference ranges for haematological andbiochemical values in llamas and alpacas (Fowler& Zinkl, 1989; Hajduk, 1992). In comparison withcommon domestic ruminants, llamas and alpacasmay have higher erythrocyte counts (11–14 ×10 12 /litre) and small mean corpuscular volume,with packed cell volumes of 0.25–0.45 litres/litre.Blood glucose levels of 108 to 156 mg/dl weremeasured in nursing 2 to 6 month old llamas comparedwith 74 to 154 mg/dl in adult llamas.Preparation for anaesthesia is the same as forsheep and goats. Bloat, regurgitation, and aspirationcan occur in llamas and, therefore, the animalsshould be fasted for 24 hours and water withheldfor 8 to 12 hours before elective anaesthesia. Youngcalves (cria) may take solid food as early as2weeks but weaning may not occur until age 4 to7 months. Fasting is not usually done in paediatricpatients because of the risk of hypoglycaemiaexcept that suckling is prevented for 30 to 60 minutesbefore anaesthesia. A rapid induction andintubation sequence is necessary for emergencyprocedures in animals that are not fasted.Severe bradycardia may develop during halothaneanaesthesia (Riebold et al., 1989) and there issome justification for premedication with atropine,0.02 mg/kg, in contrast to recommendations forsheep and goats.Anaesthetic techniquesVenepunctureJugular venepuncture for collection of blood orplacement of a catheter is not as easy as in sheep

SHEEP, GOATS & OTHER HERBIVORES 3593–4 cm dorsalto angle of ventralborder of mandible.Skin is thick.Cranial to the ventralprocess of 5th cervicalvertebra. Carotidartery nearby.FIG.13.11 Schematic drawing showing the landmarksfor jugular vein puncture in llamas.and goats. Two sites are recommended (Fig. 13.11)(Amsel et al., 1987). One site is high in the neckat the level of the mandible. An imaginary line isdrawn continuous with the ventral border ofthe mandible and the point of needle insertion is3 to 4 cm dorsal from its angle in an adult animal.Disadvantages to this site are that the overlyingskin is very thick, and movement of the headmay dislodge a needle or kink a catheter. Thesecond site is lower on the neck where the ventralprocesses of the fifth cervical vertebra can bepalpated. Placing a thumb in the depressionjust medial to the ventral process can raise thejugular vein. The overlying skin is less thick,facilitating catheter insertion. A disadvantage tothis site is that the carotid artery is nearby and canbe penetrated. Observation of pulsatile blood flowthrough the needle or catheter confirms that thecatheter is in the carotid artery and should bewithdrawn. A 14 gauge or 16 gauge, 13 cmlong catheter is inserted in adult llamas, althoughprominent valves in the vein may hinderthreading of the catheter. Other veins, such as anear vein, cephalic vein, or saphenous vein can beused in depressed, sedated, or anaesthetizedanimals.FIG.13.12 The long 35 cm Wisconsin laryngoscopeblade is useful for intubation of adult llamas;seen here incomparison with a blade used for intubation in large dogs.Endotracheal intubationThe technique for endotracheal intubation is similarto that in sheep and goats. Viewing the laryngealopening is difficult in adult llamas and alaryngoscope with a long blade is essential (e.g.35 cm Wisconsin blade, Anesthesia Medical Specialties,Santa Fe Springs, California 90670) (Fig.13.12). A 10 mm internal diameter tube can be usedin a 60 kg llama and a 12 mm in a llama of 100 kg.Intubation in large animals is made easier byinserting a metal rod inside the endotracheal tubeto stiffen it.Llamas are obligate nasal breathers and airwayobstruction may occur during anaesthesia in llamasthat are not intubated due to dorsal displacementof the soft palate, and during recovery fromanaesthesia due to nasal oedema and congestion.Nasotracheal intubation has been recommendedin llamas to provide a clear airway during anyphase of anaesthesia (Riebold et al., 1994). A longtube will be needed, such as the 40 to 55 cm longtubes manufactured for nasotracheal intubation infoals (Bivona, Gary, Indiana 46406). The internaldiameter will be about 2 mm less than the size oftube chosen for orotracheal intubation. The tubeshould be well lubricated, and lubricant containingphenylephrine can be used to causevasoconstriction in the nasal mucosa and limithaemorrhage. The tip of the tube is inserted mediallyand ventrally into the ventral nasal meatus asin horses, with the bevel directed laterally to minimizetrauma to the conchae. It is important to keep

360 ANAESTHESIA OF THE SPECIESa finger on the tube inside the nares to ensure thatthe tube remains in the ventral meatus while thetube is advanced slowly and without twisting. Ifthe tube is in the middle meatus it will impact onthe ethmoid and cause significant haemorrhage. Afurther obstruction to intubation in llamas is thelarge diverticulum, 1 cm wide and 2 cm deep, atthe caudodorsal angle of the nasopharynx. If thetip of the tube is level with the pharynx and it cannotbe advanced then the tube should be withdrawnseveral cm, redirected and advanced again.The arytenoid cartilages and epiglottis protrudeabove the soft palate into the nasopharynx.Hyperextension of the head and neck may allowthe nasotracheal tube to enter the larynx.Alternatively, a laryngoscope can be inserted intothe mouth to view the tip of the tube. While thetube is slowly and gently advanced its tip isgripped with forceps or hooked rostrally with abent stilette and directed into the larynx.Extubation after anaesthesia should be delayed, asin other ruminants, until the animal can withdrawits tongue into its mouth, and this may occur longafter the first swallowing and chewing movementsare observed.Anaesthetic agentsXylazineXylazine is often used as a sedative in doses of0.4–0.6 mg/kg intravenously. This dose will provide30 to 45 minutes of recumbency. Bradycardiawill be induced with little change in blood pressure.Sedation can be reversed with yohimbine butnot doxapram. Medetomidine produces dosedependentlight to heavy sedation in llamas,with 0.03 mg/kg i.m. inducing heavy sedationfor 1 to 2 hours. The sedative effects of medetomidinecan be reversed by i.v. atipamezole,0.125mg/kg.Lower doses of xylazine are adequate for premedicationto general anaesthesia. A commonanaesthetic combination to provide 30 minutesof anaesthesia in healthy llamas is xylazine,0.25mg/kg, i.v. followed in 10 to 15 minutes by injectionof ketamine, 2.5 mg/kg i.v. or 5 mg/kg i.m.Butorphanol, 0.1 mg/kg i.m., can be administeredat the same time as the xylazine or, 0.05 mg/kg i.v.,shortly before the ketamine. An alternative combinationis xylazine premedication followedby induction of anaesthesia with i.v. diazepam,0.1–0.2mg/kg, and ketamine 2.5 mg/kg.GuaiphenesinGuaiphenesin, up to 0.5 ml/kg of a 5% solution, isa useful adjunct to anaesthetic induction with ketaminein large llamas. Premedication facilitates theprocedure and can consist of a low dose of xylazine,or a combination of diazepam, 0.1 mg/kg,and butorphanol, 0.1 mg/kg. Guaiphenesin ismost easily injected into the catheter using a 60 mlsyringe and a 14 gauge needle. The llama will usuallyassume sternal recumbency before ketamine,2.5 mg/kg, is injected to complete induction ofanaesthesia. Dose rates of anaesthetic agents mustbe decreased for animals that are ill, for example,from urethral obstruction, peritonitis, or intestinalobstruction. Xylazine should be avoided in animalswith urethral obstruction.PropofolPropofol can be used to anaesthetize llamas butthe technique is expensive for large animals. Inductionof anaesthesia can be accomplished by2.0–3.5 mg/kg i.v. Anaesthesia may be maintainedwith an inhalation agent or by continuous infusionof propofol, 0.4 mg/kg/min. In an investigation ofcontinuous propofol anaesthesia in llamas, MAPremained high and cardiac output was not depressed(Duke et al., 1997). Hypoxaemia didnot develop even though the animals were breathingair. Additional analgesia, systemic or local, willbe necessary if the procedure is painful.Inhalation agentsHalothane or isoflurane can maintain anaesthesiaand is recommended for major surgery. Injectableagents are used to induce anaesthesia in adults,but induction with the inhalant using a facemaskis easy in paediatric animals, particularly afterpremedication with diazepam and butorphanol.Anaesthetic management is as for sheep andgoats described previously in this chapter. Thepalpebral reflex is usually retained during

SHEEP, GOATS & OTHER HERBIVORES 361anaesthesia adequate for surgery. Crinkling ofthe lower eyelid is an indication of light anaesthesia.Llamas breathe spontaneously at 10 to30 breaths/minute and appear to ventilate betterduring anaesthesia than horses or adult cattle,although IPPV should be used if monitoring identifiessevere hypoventilation.DEERThere are detailed recommendations for handlingfarmed deer, including recommendations fordesign of deer yards and raceways, deer crushesand chutes, and physical and chemical restraint(Chapman et al., 1987; Fletcher, 1995). The purposefor this section in this textbook is to describe somebasic principles of anaesthesia in deer and to referto articles for further reading on the subject.Some general guidelines for working with deerinclude talking to the deer to alert them as to yourlocation and to avoid walking through the middleof a group of deer (Fletcher, 1995). There are recommendationsthat, except for adult stags, deerare best examined in groups, as they may becomefrantic when isolated. Deer may become aggressiveand kick with their forelimbs, and occasionallybite or kick backward with their hindlimbs(Fletcher, 1995).There are considerations of special significanceto the anaesthetist. Not only are there differencesin responses between farmed deer and wildlife, inthat wild deer will require higher doses, but alsothere are differences between the species in theirresponses to both physical management andanaesthetic agents. An example given in a concisearticle on deer handling explains that fallow deer(Dama dama), unlike red deer (Cervus elaphus),respond favourably to darkened holding pens(Fletcher, 1995). Another author notes that whileroe deer (Capreolus capreolus) or fallow deer may lieimpassive when blindfolded and with their legstied, the technique is not suitable for muntjac(Muntiacus reevesi). Muntjac are small excitabledeer that will writhe, struggle and jerk violentlyagainst restraint. Extraordinary care in the methodof capture of these deer has been described(Chapman et al., 1987). Specifically, general anaesthesiawas induced with the ultra-short acting barbiturate,methohexital.Anaesthetic agentsAnaesthetic agents for sedation are frequentlyadministered by darts propelled by a gun or blowpipe,or from a syringe attached to a pole. The doserate for xylazine varies between the breeds andresponse to xylazine varies between individualswithin a breed. Xylazine alone can be administeredi.m. for sedation in penned red or fallow deerat 0.5 to 1.5 mg/kg (Fletcher, 1995), 1 mg/kg forwapiti (Cervus canadiensis), and 2 to 3 mg/kg forwhite-tailed deer (Odocoileus virginianus) and muledeer (Odocoileus hemionus) (Caulkett, 1997). Alower dosage of xylazine, 0.7 mg/kg, was satisfactoryfor capturing 104 free-ranging mule deer(Jessup et al., 1985). Reversal of sedation isachieved by administration of yohimbine, 0.1 to0.2 mg/kg, given half i.v. and half i.m., or tolazoline,2 to 4 mg/kg.Xylazine and ketamine have been used to immobilizedeer. Dosages of xylazine, 4mg/kg, and ketamine4 mg/kg, administered intramuscularly inadult fallow deer induced recumbency in less than5minutes (Stewart & English, 1990). Administrationof yohimbine 30 minutes later produced satisfactoryreversal for release after several minutes.Another recommendation is to mix 400 mg of ketaminewith 500 mg of dry xylazine powder and todose red deer at 1 to 2 ml and fallow deer up to 3 ml(Fletcher, 1995). Xylazine and ketamine may beadministered separately. The deer are sedated firstwith xylazine administered by dart and then ketamine,1 to 2 mg/kg, injected i.v. when the deer isfirst approachable (Caulkett, 1997). This decreasesthe dose of ketamine and there is less chance ofcentral nervous system excitement occurringwhen the xylazine sedation is reversed. Additionalketamine may be administered as needed.Detomidine and medetomidine, 60 to 80 µg/kgi.m., administered with ketamine, 1–2 mg/kg i.m.,have been used to sedate deer. The effects of detomidineor medetomidine can be reversed by injectionof atipamezole at a dose rate of up to fivetimes the medetomidine dose.Etorphine and acepromazine (Immobilon LA),etorphine and xylazine, and etorphine, acepromazineand xylazine combinations have been usedto immobilize a variety of species of deer (Jones,1984). Excitement has been observed with theetorphine and acepromazine combination (Jones,

362 ANAESTHESIA OF THE SPECIES1984). A high number of cardiac arrests occurred infallow deer immobilized with these combinations(Pearce & Kock, 1989).Other opioid combinations that have been usedin deer include carfentanil and xylazine and, availablein New Zealand, a premixed solution of fentanyl,azaperone, and xylazine.Anaesthesia can be deepened for major surgeryby the administration of halothane or isoflurane.The vaporizer settings are low for maintenance ofanaesthesia, 1% for halothane and 1.5% for isoflurane,particularly when detomidine or medetomidinehave been administered.Rectal temperature should be measured immediatelyand throughout the procedure. Hyperthermiawill develop in animals immobilizedoutside in the heat of the day. Monitoring pulserate and oxygen saturation is easily done with apulse oximeter and a probe applied to the tongue.ABP can be measured non-invasively using theoscillometric technique and the cuff placed aroundthe forelimb above the carpus or by using theDoppler technique and the probe over the coccygealartery. Direct measurement of ABP can bedone with a catheter in an auricular artery.Local analgesiaLocal analgesia is required for harvesting antlers.Investigation of the innervation of the antler pediclein wapiti and fallow deer identified theinfratrochlear and zygomaticotemporal nerves asthe largest nerves travelling to the pedicle(Woodbury & Haigh, 1996). In some animals, theauriculopalpebral nerve supplied prominent dorsalbranches to the lateral or caudal aspects of thepedicle. There should be no sensory fibres in thisnerve. However, there have been reports that blockof the auriculopalpebral nerve has achieved localanaesthesia in a small number of deer in whichinadequate analgesia was produced by conventionalnerve block. No other nerves were found toinnervate the antler. Branches of the second cervicalnerve were observed to terminate near the baseof the ear (Woodbury & Haigh, 1996). Thus, recommendationsfor nerve block are the conventionalblock as described earlier for sheep and goats,increasing the volume of lignocaine at each site to5 ml and depositing the solution deeper, 2 to 3 cm,for the zygomaticotemporal nerve. Local anaestheticsolution can also be injected over the zygomaticarch, halfway between the base of the earand the lateral canthus. A ring block can be includedshould additional analgesia be needed forantler removal.CAMELSHandling camels can be dangerous and particularcaution must be observed during the breeding seasonwhen males may be intractable and vicious.Males may press a person to the ground with theirneck and body, a crushing effect, or they may bite,causing severe even fatal injuries (Ogunbodede &Arotiba, 1997). Most experienced anaesthetistsprefer whenever possible to work on domesticatedcamels made by their handlers to sit for thisreduces the risk to personnel and to the animal.Tying the forelimb is a common mode of restraint(Fig. 13.13) in animals not trained to lie down oncommand. Also of interest to the anaesthetist,camels may be susceptible to toxicity from somedrugs at doses used commonly in other ruminants.Although the pharmacokinetics of a variety ofnon-steroidal drugs and antibiotics have beenpublished in recent years, very little information isavailable about anaesthetic agents.Heart rates in unsedated resting camels are40–50 beats/min, mean arterial pressures 130–140 mmHg, and respiratory rates 6–16 breaths/min. Hematologic and biochemical blood valuesfor camels (Camelus dromedarius) have been published(Snow et al., 1988; Nazefi & Maleki, 1998).FIG.13.13 Camels not trained to lie down on commandcan often be restrained by hobbling the front leg.

SHEEP, GOATS & OTHER HERBIVORES 363Measurements made after racing show that, incontrast to dogs and horses, no significant increasein haematocrit occurs after exercise due to releaseof red cells from the spleen. Although packed cellvolume is on average 0.33 litres/litre, camelerythrocytes have a very high mean corpuscularhaemoglobin concentration.Voluntary regurgitation of rumen contents mayoccur in agitated camels and withholding of roughagefor 48 hours and concentrate for 24 hoursbefore anaesthesia has been recommended.Domestic camels may sit on command (couched)which avoids the need for casting or the risk ofinjury with ataxia or falling after administration ofanaesthetic agents.Local and regional analgesiaNerve blocks of the hindlimb in camels have beendescribed, including the topographical anatomyand technique to block the peroneal, tibial, andplantar nerves (Dudi et al., 1984). Desensitization ofthe digit can also be achieved using intravenousregional analgesia by injecting 60 ml of 2% lignocaine(without adrenaline) distal to a tourniquet(Purohit et al., 1985). Xylazine sedation has beencombined with a line block with 2% lignocaine toprovide satisfactory restraint and analgesia for caesariansection to remove dead foetuses (Elias, 1991).Xylazine, 0.4 mg/kg i.m. , given to healthy adultcamels (Camelus dromedarius) (Peshin et al., 1980)and Camelus bactrianus (Custer et al., 1977)) resultsin sternal recumbency in 11–15 minutes and arecumbency time of 1–2 hours. The cardiovasculareffects of xylazine administration are qualitativelysimilar to those in sheep and goats in that xylazineinduces bradycardia, an increase in CVP, and asmall but statistically significant decrease in MAP,bottoming out at 45 minutes.Smaller doses of xylazine, 0.25 mg/kg, havebeen used in combination with ketamine, 2.5mg/kgi.m., for sedation and analgesia in the dromedarycamel (White et al., 1987). Loss of facial expression,drooping of the lower lip, weaving of the head, anddrooling of saliva occur at the onset of sedation.Most camels lay their head and neck on the groundand would assume lateral recumbency if allowed.In six camels (Camelus dromedarius) satisfactoryanaesthesia for tracheal intubation was achievedwith a mean thiopental dose of 7.25 mg/kg (Singhet al., 1994). Subsequent maintenance of anaesthesiawith halothane resulted in hypoventilationand a significant decrease in ABP. The camelsrecovered from anaesthesia on average 40 minutesafter the halothane was discontinued. The authorsnoted that O 2 supplementation was necessaryduring recovery from anaesthesia to preventhypoxaemia. Anaesthesia can also be inducedwith a mixture of thiopental and guaiphenesinprior to halothane anaesthesia. In camels injectedi.m. with xylazine, 0.25 mg/kg, 30 minutespreviously, 1.0–2.3 ml/kg of thiopental-guaiphenesin(2 g thiopental in 1 litre 5% guaiphenesin)given rapidly i.v. produces sufficient relaxationfor intubation (White et al., 1986). IPPV was employedto treat hypoventilation and MAPs weresatisfactory.Intubation of the trachea can be done manuallyusing the same techniques that are used in cattle.Male dromedary camels have a dulaa (palatal flapor goola pouch) which extends from the soft palate(White et al., 1986).ELEPHANTSTrained elephants are usually relatively quiet andintravenous injection can be made into an ear vein.Drug administration to free-ranging animals is bydart gun. Accurate estimates of body weight areuseful when calculating drug dosages in anattempt to produce consistent anaesthetic effects.Body measurements from 75 Asian elephants(Elephas maximus) from 1 to 57 years of age wereused to calculate correlations with body weight(Hile et al., 1997). The authors concluded that inAsian elephants the heart girth is the best predictorof weight. Heart girth (cm) was measured justbehind the front legs using cotton twine. Weightwas predicted using the equation:Weight (kg) = 18.0 ( heart girth) – 3336.Measurement of pad circumference was not a usefulpredictor of weight.ImmobilizationEtorphine has frequently been used to immobilizeelephants. Free ranging African elephants

364 ANAESTHESIA OF THE SPECIES(Loxodonta africana) were immobilized by i.m.injection by darts with 9.5 ± 0.5 mg etorphine(Osofsky, 1997) or 3, 6, or 9 mg of etorphine and 30,60, or 100 mg of azaperone according to size injuvenile elephants (mean weight 672 kg) (Still et al.,1996). The mean time to recumbency was 9 minutes.Additional etorphine had to be administeredintravenously to maintain immobilization fortransportation. All elephants recovered uneventfullyafter reversal by i.v. diprenorphine atapproximately three times the dose of etorphineadministered. In another report, etorphine,0.002mg/kg, was given i.m. or i.v. to provide satisfactoryimmobilization for laparotomy for castration(Foerner et al., 1994). Supplements of 1 mg ofetorphine were injected as needed to maintainimmobilization.Up to one-third of the elephants immobilizedwith etorphine are reported to be hypoxaemicas determined by pulse oximetry or blood gasanalysis. At an average respiratory rate of 9 breathsper minute, PaCO 2 was only mildly to moderatelyincreased. The average PaO 2 of the immobilizedelephants in one study, 10.0 ± 1.7 kPa (75 ±13 mmHg) (Still et al., 1996), was lower than previouslyreported for recumbent elephants, 11.2 ±0.4 kPa (84 ± 3 mmHg), or standing unpremedicatedelephants, 12.8 ± 0.3 kPa (96 ± 2 mmHg)(Honeyman et al., 1992). Hypoxaemia occurredonly in elephants with a body mass

SHEEP, GOATS & OTHER HERBIVORES 365administration of isoflurane. Anaesthesia timeswere from 2.4 to 3.3hours and the elephant recoveredsatisfactorily after each episode. O 2 was insufflatedat 60 l/min into the endotracheal tube duringrecovery from anaesthesia. Residual etorphinewas reversed by administration of diprenorphine25 to 40 minutes after isoflurane was discontinued.REFERENCESAlahuhta, S., Kangas-Saarela, T., Hollmen, A.I. andEdstrom, H.H. (1990) Visceral pain during caesariansection under spinal and epidural anaesthesia withbupivacaine. Acta Anaesthesiologica Scandinavica34: 95–98.Aminkov, B.Y. and Hubenov, H.D. (1995) The effect ofxylazine epidural anaesthesia on blood gas and acidbaseparameters in rams. British Veterinary Journal151: 579–585.Amsel, S.I., Kainer, R.A. and Johnson, L.W. (1987)Choosing the best site to perform venipuncture in allama. Veterinary Medicine 82: 535–536.Barrington, G.M., Meyer, T.F. and Parish, S.M. 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366 ANAESTHESIA OF THE SPECIESelephants. Journal of Zoo and Wildlife Medicine23: 205–210.Howard, B.W., Lagutchik, M.S., Januszkiewicz, A.J. andMartin, D.G. (1990) The cardiovascular response ofsheep to tiletamine-zolazepam and butorphanoltartrate anesthesia. Veterinary Surgery 19: 461–467.Jessup, D.A. and Lance, W.R. (1982) What veterinariansshould know about South American camelids.California Veterinarian 11: 12–18.Jessup, D.A., Jones, K., Mohr, R. and Kucera, T. (1985)Yohimbine antagonism to xylazine in free-rangingmule deer and desert bighorn sheep. Journal of theAmerican Veterinary Medical Association 187: 1251–1253.Jones, D.M. (1984) Physical and chemical methods ofcapturing deer. Veterinary Record 114: 109–112.Kyles, A.E., Waterman, A.E. and Livingston, A. (1995)Antinociceptive activity of midazolam in sheep.Journal of Veterinary Pharmacology and Therapeutics18: 54–60.Laitinen, O.M. 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Anaesthesia of the pig14INTRODUCTIONSurgery may be carried out on the farm using eitherlocal analgesia or general anaesthesia but, where economicallypossible, for all other than minor surgeryit is better to have the pig transported to a placewith complete surgical facilities. Where local analgesiais used, the pig is usually first heavily sedatedor even lightly anaesthetized to prevent theloud squealing noises which these animals makewhen restrained. When general anaesthesia is employedunder farm conditions, simple methods givingshort-term anaesthesia suffice, as surgery isusually limited in complexity. However, the pig isnow also often used as an experimental animal in researchprojects involving long and complicated surgeryand sophisticated techniques, possibly evenincluding cardiopulmonary bypass, may be required.Pigs presented for anaesthesia range in sizefrom small newborn piglets to adult boars weighing350 kg, and the methods of restraint andadministration of anaesthetics must be variedaccordingly. Whilst small pigs are easily restrained,large sows and boars may prove both difficultand dangerous. Large pigs are usuallyrestrained by a rope or wire snare around theupper jaw, behind the canine teeth (Fig. 14.1).In most cases the pig will try to escape bypulling back against this rope or snare and thusimmobilizes itself, but this method does not workif the animal moves forward to attack (as a sowFIG.14.1 Restraint of the pig by a snare applied aroundthe upper jaw.attempting to defend her litter may do). Smallerpigs are usually restrained on their sides by graspingthe undermost legs and leaning on the body.Pigs are easily trained and, at a research establishment,the problems of restraint are greatly reducedby very frequent, regular handling. In a largeintensive farming unit, however, there is a lackof individual handling and some animals maybe extremely difficult to control by physicalmeans.367

368 ANAESTHESIA OF THE SPECIESMost anaesthetists consider that when generalanaesthetics are administered with due care pigsare good subjects. Although they resent restraint,as is shown by the struggling and loud squealswhich they produce, this does not seem to result inadrenaline release with the attendant dangers duringsubsequent anaesthesia. Recovery from anaesthesiais usually calm. As they have little body hair,pigs are liable to develop hypothermia whensedated or anaesthetized, but this lack of hair doesenable the anaesthetist to assess the state ofperipheral circulation by monitoring the skincolour. Pigs tend to be fatter than most other farmanimals and adipose tissue forms a depot foranaesthetics. The fatty nature of the tissue alsomakes accurate i.m. injections more difficult inthese animals and necessitates the use of long needlesto reach the muscle through the fatty tissue.The shape of the pig’s head, together with the fatin the pharyngeal region (especially in VietnamesePot-bellied pigs) coupled with the small larynxand trachea, makes respiratory obstruction likelyin both sedated and anaesthetized animals.Patency of the airway in the absence of endotrachealintubation is best maintained by applyingpressure behind the vertical ramus of the mandibleand thus pushing the jaw forward, while the tongueis drawn out between the incisor teeth (Fig. 14.2).Salivation, even if not excessive, can contributeto airway obstruction so anticholinergic premedicationis usually given before general anaesthesiaunless there are contraindications such as preexistingtachycardia or pyrexia.PORCINE MALIGNANTHYPERTHERMIAAlthough in the vast majority of pigs generalanaesthesia presents few problems other thanthose associated with the maintenance of a clearairway, some strains and breeds suffer from a biochemicalmyopathy which manifests itself duringgeneral anaesthesia with some anaesthetic andancillary agents. Hall et al. (1966) reported itsoccurrence in Landrace cross pigs following theuse of suxamethonium during halothane anaesthesia,but it was later found that it could occurwithout the administration of suxamethonium.FIG.14.2 Maintaining a clear airway by pushing forwardon the vertical ramus of the mandible with the tonguedrawn forward on the mouth.For ease of photography,inthis illustration the mask is held firmly on the face by thethumb,but the position of the hand is usually reversed,thethumb being used to push on the mandible and the fingersto hold the mask on the face.Breeding experiments with Landrace cross pigsshowed the abnormality to be inherited as an autosomaldominant with variable penetrance, occasionallitters being found without susceptibleanimals. In some litters, however, piglets diedbefore testing with a non-lethal test procedurewhich had been developed (Hall et al., 1972) so thisfinding must be treated with some reserve. It isalso possible that two genes might have beeninvolved but, unfortunately, due to withdrawalof funding, further investigation of this wasimpossible.The abnormal response of these pigs to anaestheticand other drugs is characterized by thedevelopment of generalized muscle rigidity, asevere and sustained rise in body temperature,hyperkalaemia and metabolic acidosis. Since thefirst report of the porcine syndrome there havebeen numerous other reports of similar abnormalresponses to anaesthetic agents, both in humansand animals and it is generally agreed that thesyndrome has certain resemblances to the ‘stress

THE PIG 369FIG.14.3 Rigidity of limbs in a pig with developed porcine malignant hyperthermia.reaction’ seen in Pietrain and Poland-China pigs.There are, however, some striking differencesbetween the syndrome as manifested in variouspig breeds and strains. For example, in the Poland-China and Pietrain breeds dyspnoea, hyperthermiaand immediate rigor mortis can be induced byenvironmental stress associated with exercise,transportation and high environmental temperatures,whereas Landrace and Landrace cross pigsdevelop the syndrome only when anaesthetized.It has been suggested that malignant hyperthermiain man could be a syndrome resulting frommore than one defect, and the same may be true forthe porcine syndrome. It seems likely that it is resistanceor susceptibility to triggering factors whichdiffers, and that the final metabolic derangementwhich leads to death is common to all. While thepig has proved to be a valuable experimental animalfor the study of this condition, great caution isneeded in attempting to transpose results obtainedin one breed or strain of pigs to another breed orstrain, to another species of animal, or to man.Early clinical findings suggested that the primaryabnormality lies in the voluntary muscle ofaffected animals and attempts have been made tofind a biochemical ‘marker’ which could supportthis suggestion and which might serve to identifyexperimental animals (and more particularlyhuman beings) at risk. Raised serum creatinephosphokinase (CPK) occurs in a number ofmyopathies both in humans and in experimentalanimals and serum levels of this enzyme werestudied in Landrace cross pigs by Woolf et al.(1970) who found that raised CPK levels inunanaesthetized animals had a fair predictivevalue for the development of abnormal musclecontracture following induction of anaesthesiawith halothane and challenge with suxamethonium(Hall et al., 1972). Of 34 closely related pigsstudied, 25 had serum CPK levels > 250 units/mland 20 of these were subsequently found to reactpositively to challenge. Clearly finding of a CPKlevel of < 250 units/ml does not rule out the possibilityof an abnormal reaction, but the chances ofthis happening are much lower.It must be emphasized that the clinical veterinaryanaesthetist is very unlikely to encountercases of porcine malignant hyperthermia except inthe Poland-China and Pietrain breeds, but it mayoccur in Large White and Landrace pigs (particularlyin view of the modern practice of breedingfrom boars known to carry the trait because of thebelief that their offspring may have faster growthrates). However, anaesthetists should be aware ofthe existence of this condition, be able to recognizeits development during anaesthesia and, wherepossible, treat it. In a typical case, where a susceptiblepig is given a triggering agent, its musclesdevelop contracture making the animal very stiffor even rigid (Fig. 14.3). Often the first sign the

370 ANAESTHESIA OF THE SPECIESFIG.14.4 Spreading apart of the digits in a pig developing porcine malignant hyperthermia.anaesthetist notices is a spreading apart of the digits(Fig. 14.4). Next, the body temperature starts torise and the skin often shows blotchy reddening. Ifno attempt is made to treat the condition, the bodytemperature continues to rise (rectal temperaturesof over 108 ° F have been recorded); eventually respirationceases and death ensues. Presumablydeath is due to cellular hypoxia, for at temperaturesabove 42°C oxygen utilization exceeds oxygensupply.Dantrolene sodium, a skeletal muscle relaxant,given orally in doses of 2 to 5 mg/kg 6 to 8 hoursbefore the induction of anaesthesia, may preventthe onset of the syndrome in susceptible pigsand i.v. in doses of 2 to 10 mg/kg, has provedof some use in treating the established condition.Unfortunately dantrolene sodium is expensive.It has a very limited shelf-life and, in general,keeping it in readiness for the treatment of thisuncommon porcine condition cannot be justifiedon economic grounds although it certainly isfor man.Induction of anaesthesia with Saffan affordssome protection against the development of thesyndrome in some strains of susceptible animals(Hall et al., 1972). Symptomatic treatment includesrapid termination of the inhalation anaesthetic andthe administration of pure oxygen, preferablythrough a ‘clean’ anaesthetic system, the administrationof i.v. sodium bicarbonate (2 to 4mEq/kg i.v.)and whole body cooling with cold water appliedto the skin. Intravenous dantrolene may be given ifavailable.SEDATIONThe pig’s reaction to restraint (struggling accompaniedby ear-splitting squeals) is unpleasant forall concerned and, therefore, sedation is widelyused to facilitate all handling and minor procedures,as well as for restraint prior to local or generalanaesthesia. In pigs, α 2 adrenoceptor agonistsseem to be useful in smoothing reactions to ketaminebut, for reasons as yet unknown, they areotherwise generally ineffective as sedatives.SEDATIVE AGENTS EMPLOYED IN PIGSAzaperoneThis extremely safe butyrophenone drug is inexpensiveand so effective in pigs that other sedativesare now seldom used in these animals. It ismarketed both to the veterinary profession forclinical use and directly to farmers who use it tocontrol fighting when mixing litters in intensivefattening units.Azaperone must be given by deep i.m. injection,the neck muscles behind the ear usually proving tobe the most convenient and best site; s.c. injectionis ineffective and i.v. injection results in a phase ofviolent excitement. Injection into regions likely tobe used for human food (e.g. the hams) shouldalways be avoided. The doses used depend on theeffects sought and range from 1 to 8 mg/kg, but itis recommended that a dose of 1 mg/kg is notexceeded for adult boars as higher doses cause

THE PIG 371protrusion of the penis with the risk of subsequentdamage to that organ. Following an i.m. injectionof 1 to 8mg/kg of azaperone, the pig should be leftundisturbed for 20 minutes, as interference beforethis time may provoke an excitement reaction.Excitement may occur during this induction phaseeven in the absence of stimulation, but it is usuallymild and rarely of clinical significance. After theinduction period of some 20 minutes, pigs aredeeply sedated and handling for the administrationof other drugs or minor procedures is greatlyfacilitated.Azaperone causes vasodilatation resulting in asmall fall in arterial blood pressure, and someslight respiratory stimulation. Vasodilatation ofcutaneous vessels makes sedated pigs particularlylikely to develop hypothermia in a cold environmentso warm surroundings are essential, but thedilated ear veins are easy to enter for i.v. injectionof drugs.less when handled and are much less likely to dislodgethe i.v. needle by head-shaking when injectionis made. Acepromazine may be given by i.v.injection but this may be followed by venousthrombosis unless very dilute solutions are used.When given i.v. the drug should be allowed 10 to20 minutes to produce its full effects. Hyperpnoealasting for about 15 minutes may follow i.v. injection,but the reason for this is unknown.Dissociative agentsPhencyclidine was used very successfully as asedative for pigs for some years until the hallucinatoryeffects produced in man ingesting the drugled to a ban of the use of the drug in food animals.Phencyclidine has been withdrawn from the marketand the dissociative agent in current use, ketamine,is generally used as an anaesthetic ratherthan as a sedative; low doses are analgesic.DroperidolThe butyrophenone compound, droperidol, hasbeen used in pigs and doses of 0.1 to 0.4 mg/kggive similar sedation to that produced by azaperone.Butyrophenone/analgesic drug mixtureshave been used and fentanyl/droperidol producebetter sedation than droperidol alone. At theCambridge School a combination of i.m. droperidol(0.5 mg/kg) with midazolam (0.3 mg/kg) givenseparately, or where appropriate, from the samesyringe, produces ideal sedation for radiography,lancing of abscesses, etc. (P.G.C. Jackson, personalcommunication). Dependable sedation of approximately15 min duration follows some 10 minutesfrom the time of injection, but it is important toleave the pig undisturbed whilst the effects aredeveloping. As with ketamine, sudden awakeningwithout prior warning may occur.AcepromazinePhenothiazine derivatives are not as effective inpigs as they are in some other species of animal.However, pigs are more easily restrained for i.v.injection if first given an i.m. dose of 0.03 to0.10 mg/kg before venepuncture is attempted.Under the influence of acepromazine they squealGENERAL ANAESTHESIAPREPARATION FOR GENERALANAESTHESIAIn pigs, 6 to 8 hours fasting and 2 hours deprivationof water is usually adequate to ensure that thestomach is empty. Vomiting at induction or duringrecovery is rare in pigs (although it used to be seenregularly in pigs recovering from cylcopropaneanaesthesia) but a full stomach exerts pressure onthe diaphragm and reduces respiratory efficiency.The majority of surgery carried out in pigs,whether clinical or experimental, is elective, andfluid deficits are seldom present before anaesthesia.An i.v. infusion may be needed, however, beforeanaesthesia for the correction of a strangulatedhernia, for example. Details of existing drugtherapy such as antibiotic food additives, oranthelminitics, should be noted – especially ifneuromuscular blocking drugs whose action theymay lengthen are to be used in the anaesthetictechnique.PremedicationDuring general anaesthesia salivation, even if notexcessive, may cause respiratory obstruction.

372 ANAESTHESIA OF THE SPECIESAtropine, i.v. or i.m. in doses 0.3 to 2.4 mg (totaldose), or glycopyrrolate (0.2 to 2.0 mg total dose),depending on the size of the pig, will usually controlthis salivation.The degree of sedation required depends on theanaesthetic technique which is to follow. Someanaesthetists prefer to dispense with sedation atthis stage while others use it to facilitate theadministration of the anaesthetic and to reduce thesquealing and struggling which would otherwiseoccur during inhalation anaesthetic induction.Only rarely is there any need for analgesics to beincluded in the premedication but if required theymay be employed in slightly larger doses than areused in dogs. It is probable that azaperone is themost widely used premedicant drug for porcineanaesthesia. As already mentioned, it is given i.m.in doses of 1 to 8 mg/kg according to the degree ofsedation required.Intravenous techniqueInjections are best made into auricular veins on theexternal aspect of the ear flap. Small pigs arerestrained on their side on the table and usuallytwo assistants are needed, one gripping the legs,FIG.14.5 Distension of the ear flap veins by theapplication of a rubber band around the base of the ear.whilst the second holds the uppermost ear at thebase of the conchal cartilage and applies pressureover the vein as near to the base of the ear as possible.If a second assistant is not available a rubberband is applied around the base of the ear flap. Inlarge pigs, a noose is applied around the upper jawbehind the tusks as previously described (see Fig.14.1). As in small pigs, the ear veins are distendedby the application of pressure as near to the base ofthe ear flap as possible.Once the skin of the ear flap over the vein hasbeen cleansed, the veins are usually easily visible(Fig.14.5) but if necessary they can be made moreobvious by gentle slapping and brisk rubbing ofthe ear flap with an alcohol-soaked gauze swab.Venepuncture is then carried out using a needleabout 2.5 cm long and depending on the calibreof the vessel to be entered, 21 to 23 gauge (0.6 to0.65 mm). In large pigs blood can be aspirated intoan attached syringe once the needle has beeninserted into the lumen of the vein but in smallpigs the amount of blood in the vein between thepoints of pressure and the needle point may be sosmall that it is impossible to withdraw any into thesyringe. In such cases injection must be attemptedand if the needle point is not in the vein a subcutaneousbleb will develop. When it is certain that theneedle is in the vein the pressure is released (if arubber band has been applied to the base of theear flap the band must be cut with scissors) and theinjection made. It will be noticed that the injectedfluid washes the blood from the vein and thisaffords further evidence that the needle is correctlyplaced in the lumen of vessel.Introduction of a catheter into an ear vein is notdifficult (Fig. 14.6) but these veins are not very convenientfor the administration of large volumesfluid. Fortunately, infusions of large volumes areseldom needed but if they are anticipated to benecessary it is usually best to implant surgically acatheter into the jugular vein of the anaesthetizedpig as the subcutaneous fat makes percutaneousplacement difficult. Some workers prefer tocatheterize the anterior vena cava by a blind technique.Small pigs are restrained on their backs in aV-shaped trough with the neck fully extended andthe head hanging down. The forelegs are drawnback and a 5 to 7.5 cm long 16 s.w.g. (1.65 mm)needle pushed through the skin in the depression

THE PIG 373FIG.14.7 Site for the introduction of a needle topenetrate the anterior vena cava.The needle tip isadvanced towards an imaginary point midway between thescapulae.which can be palpated just lateral to the anteriorangle of the sternum and formed by the anglebetween the first rib and trachea. The needle isdirected towards an imaginary point midwaybetween the scapulae and advanced until bloodcan be freely aspirated through it when a syringeis attached. A fine plastic catheter is then threadedthrough the needle into the anterior vena cava andafter its position has been verified by aspirationof blood through it, or by radiography, theneedle is completely withdrawn and the cathetersecured in position with a skin suture. In large animalsthe procedure is carried out with the animalstanding and hanging back on a nose snare. It isalways important to ensure that the head does notdeviate from the midline and that the neck is wellextended (Fig. 14.7).Intraperitoneal injectionFIG.14.6 Stages in the introduction of a catheter into anear vein of a pig.The stitch securing the catheter does notpenetrate the ear cartilage.‘Super-glue’ may be used as analternative to stitching.This method of administration of anaestheticdrugs is very far from ideal, but it is sometimesemployed by the laboratory worker and the lessskilled veterinarian. Response is variable, andaccidental injection into the liver, kidney or gutlumen may follow. The injection of irritant solutionsmay lead to the subsequent formation ofintraperitoneal adhesions. Preferably, pigs shouldbe starved for 24 hours to reduce the gut volumebefore injection is made. The animal is thenrestrained on its back or by its hind legs, and an

374 ANAESTHESIA OF THE SPECIESarea of skin in the region of the umbilicus isclipped and cleaned. A needle is inserted 2 to 5 cmfrom the midline at the level of the umbilicus andinjection made. A complete absence of resistance topressure on the plunger of the syringe indicatesthat the solution is being injected into the peritonealcavity or, possibly, into the lumen of the gut.AEndotracheal intubationEndotracheal intubation in the pig is not as easy asin most other domestic animals. It is particularlydifficult in the extremely brachycephalic pot-belliedpig. The shape and size of the head and mouthmake the use of a laryngoscope difficult. The rimaglottis is extremely small and the larynx is set at anangle to the trachea, causing difficulty in passingthe tube beyond the cricoid ring (Fig. 14.8).Laryngeal spasm is easily provoked so atraumaticintubation must be carried out under deep generalanaesthesia with local analgesic spray of thecords, or with the aid of a neuromuscular blockingagent.The sizes of endotracheal tubes suitable for pigsare unexpectedly small when compared withthose used in dogs of a similar body weight. A6mm tube may be the largest which can be passedin a pig weighing about 25 kg; a 9 mm tube is suitablefor a 50 kg animal; large boars and sows mayaccommodate tubes of 14 to 16 mm diameter. Pot-BCArytenoid cartilageLumen of tracheaLateral ventricleof larynxEndotrachealtube (cuffed)Opening oflateral ventricleEpiglottisThyroid cartilageFIG.14.8 Saggital section of pig’s head to show principalstructures in relation to the passage of an endotrachealtube.The lumen of the trachea runs at an angle to the lineof the glottic opening.FIG.14.9 Apparatus needed for endotracheal intubationin the pig.A Note the malleable wire stilette inside thetube but not protruding from its bevelled end;B the use ofthe laryngoscope to elevate the lower jaw and displace thetongue to one side;C tube tied in position with tapearound the lower jaw and cuff inflated.

THE PIG 375bellied pigs can only be intubated with smallerdiameter tubes – a 90 kg animal can only accommodatea 9 mm diameter tube. Introduction of thetube may be made easier by the use of a malleablestilette such as a copper rod with one end carefullyrounded or covered to prevent damage to themucosa of the larynx or trachea. The stilette isplaced inside the endotracheal tube and a moveableside arm adjusted to ensure that the tip doesnot protrude beyond the end of the tube (Fig. 14.9).Whenever a tube is reinforced in this way caremust be taken not to use force in its introduction,as damage to the laryngeal mucosa with subsequentoedema and, after extubation, respiratoryobstruction, can easily occur. Laryngoscopesdesigned for use in man, as used in dogs, are suitablefor small pigs, but in large ones the weight ofthe lower jaw may make its elevation almostimpossible and the Rowson laryngoscope may beneeded to expose the larynx to view.The easiest position in which to intubate theanaesthetized pig using a standard laryngoscopeblade is with the pig supine and the neck and headfully extended. An assistant pulls on the tongueand fixes the upper jaw while the laryngoscope isintroduced and the larynx brought into view byvertical lifting of the tongue and lower jaw, noleverage being exerted (Fig 14.10). Under directvision the tube is passed between the vocal cordsand kept dorsal to the middle ventricle of the larynx.If its progress is arrested at the cricoid ring,the stilette must be partially withdrawn and thehead flexed slightly on the neck. The tube maythen be advanced gently into the trachea. An alternativeis to introduce a stilette about three times thelength of the endotracheal tube it is intended touse through the larynx under direct vision andthen to ‘railroad’ the tube over it into the trachea.Endotracheal intubation in the pig is greatlyfacilitated by the use of neuromuscular blockingdrugs, such as suxamethonium, which relax thejaw muscles and prevent the larynx from goinginto spasm. The anaesthetized pig is given oxygento breathe through a face mask and the chosenneuromuscular blocker given i.v. The pig is intubatedas soon as the jaw muscles relax and IPPV iscarried out until spontaneous respiration isresumed. When suxamethonium is injected, spontaneousrespiration returns within 1 to 2 min.FIG.14.10 View of the pig’s larynx when a standard typelaryngoscope is used correctly in the supine animal.As canbe seen,the laryngoscope blade is used to elevate the baseof the tongue and does not come into contact with theepiglottis.The epiglottis is often so soft and flexible thatunless due care is taken it folds back into the glotticopening as the tube is passed.Should an attempt at intubation fail, small pigsmay easily be ventilated with pure oxygen bysqueezing of the reservoir bag of the anaestheticapparatus while a face mask is correctly applied(Fig. 14.2). Applying IPPV in this way is more difficultin adult sows and boars, so it is recommendedthat neuromuscular blocking drugs are only usedin these larger animals by anaesthetists experiencedat endotracheal intubation and capable ofventilating large individuals through a face-mask.TECHNIQUES OF GENERAL ANAESTHESIAIN PIGSAlthough the pig is a good subject for generalanaesthesia the anaesthetist may find problems in

376 ANAESTHESIA OF THE SPECIESmaintaining a clear airway and spontaneousbreathing in non-intubated animals. When dealingwith fat pigs, cessation of breathing is a commoncomplication of deep anaesthesia. A striking featureof this apparent respiratory failure is that it isdifferent from that seen in other species, for expulsionof air from the lungs by pressure on theabdomen is immediately followed by a spontaneousdeep inspiration of the type seen when thereis some mechanical obstruction to respiration duringanaesthesia. It is possible that the position ofthe head is enough to cause pressure on the larynxsufficient to arrest breathing. The animal’s headshould be placed at a natural angle to the neck andIPPV applied. In unintubated animals this is performedby applying pressure to the abdomenabout every 4 seconds. Unless spontaneous breathingreturns within 1 to 2 minutes, endotrachealintubation to facilitate IPPV should be considered.If IPPV is carried out through a closely appliedface mask care must be taken to limit the pressuresapplied to avoid inflation of the stomach.The prudent anaesthetist avoids trouble byavoiding the need to produce deep anaesthesia inspontaneously breathing animals – if necessary bythe simultaneous use of techniques of local analgesiawhen light general anaesthesia does not sufficeon its own.Intravenous anaesthesiaThe i.v. injection of suitable agents into an alreadysedated animal is an excellent way of inducinggeneral anaesthesia in pigs. Under farm conditionsit may be desirable to maintain anaesthesia by useof intravenous drugs but if suitable apparatus isavailable anaesthesia can be maintained even onfarms, with inhalation agents. Numerous agentsare available for induction of anaesthesia by the i.v.route and many of them can be used to maintainanaesthesia in situations where this is necessary. Inpigs, some of these agents may also be administeredby IP injection, but this route is not to be recommended.MetomidateThis hypnotic drug has been used on theContinent of Europe, usually in combination withazaperone, for the production of deep narcosis(short of general anaesthesia) in pigs both underfield conditions and prior to the use of moresophisticated methods in the operating theatre.Ideally, metomidate is given i.v. at dose rates of3.3mg/kg about 20 minutes after i.m. injection of2 mg/kg azaperone. Often the pig moves as themetomidate is injected and this may be a responseto pain for the i.v. injection of the related drug, etomidate,is known to cause pain in man. Followingi.v. injection of metomidate after azaperone pigsbecome recumbent and will remain so for some10 to 20 min. Respiration is well maintained andfurther doses of metomidate can be given as neededto prolong recumbency. Analgesia is very limitedwith this combination of drugs and painfulstimuli sometimes result in dramatic, even if shortlived,awakening, so it is advisable to utilize someform of analgesia, or even physical restraint, toenable surgery to be carried out. The combinationof azaperone and metomidate is compatible withall inhalation and neuromuscular blocking agentsused in anaesthesia so they may be used subsequentlyas needed.In some centres anaesthesia associated withonly minimal analgesia has been maintained bythe continuous i.v. infusion of azaperone(2mg/kg/hour) and metomidate (8 mg/kg/hour).It is claimed that this technique offers a safe alternativewhen facilities for administration of inhalationagents are not available, although recoverycan be prolonged.It is possible to give azaperone i.p. or i.m. andmetomidate i.p. at the same time. Narcosis followsabout 20 minutes after injection but this can resultin peritonitis and formation of intra-abdominaladhesions.Thiopental sodiumAnaesthesia can be induced in pigs by the i.v. injectionof minimal (5 to 10 mg/kg) quantities of a2.5% solution of thiopental. As in all other speciesof animal, larger doses or incremental doses arecumulative and can result in delay in recovery.The quantity of thiopental taken to inducemedium depth surgical anaesthesia and the durationof the anaesthetic period are chiefly governedby the speed at which the i.v. injection is made.

THE PIG 377When rapid injection techniques are practised inhealthy pigs, the quantity used will be surprisinglysmall, and the recovery period short. Surgicalanaesthesia can be induced in non-premedicatedsows weighing about 100 kg by injection of nomore than 500 mg of the drug. Moreover, it hasbeen observed that use of a 2.5% solution decreasesthe total dose required for any operation.Induction of anaesthesia with thiopental sodium isgreatly facilitated by azaperone premedication.Provided that the pig is left undisturbed for20 minutes after injection of the azaperone, controlledinjection into an ear vein is easy and completeanaesthesia can be obtained with very low quantitiesof a 2.5% solution of thiopental. It seems thatbutyrophenone antagonizes the respiratorydepressant effect of thiopental but this clinicalimpression still awaits controlled investigation.As with all barbiturate anaesthetics, respirationmay fail with the onset of anaesthesia. When rapidinjection techniques are used this period of apnoeais short and should not necessitate use of IPPV.Apnoea of more than a few seconds durationmust, of course, be treated by IPPV and, providedthis is applied efficiently, spontaneous breathingsoon returns. Recovery after a very great overdoseof thiopental may be expected if efficient IPPV isperformed until the concentration of thiopental inthe brain has diminished.Methohexital sodiumProvided the anaesthetist is aware of the specialcharacteristics of methohexital (such as its tendencyto produce muscle tremors during inductionof anaesthesia) this agent can be used quite safelyin pigs. Anaesthesia can be produced in unsedatedanimals by i.v. injection of 5 to 6 mg/kg as a 2.5%solution and recovery is complete 10 to 15 minafter injection of a single dose.Premedication with azaperone reduces the doseof methohexital required and enables small incrementaldoses to be used to prolong anaesthesiawithout delay in recovery.Pentobarbital sodiumThis drug still has a place for surgery carried outon farms and in experimental laboratories. Themost satisfactory method of administration of pentobarbitalis slow i.v. injection into an ear vein untilthe desired degree of the central nervous systemdepression is obtained. However, for non-survivalexperiments intraperitoneal injection using a computeddose, or for castration intratesticular injectionof large doses, may be useful alternatives forthe inexperienced anaesthetist.For healthy, unsedated male and female pigs upto 50 kg (approx 1 cwt) live weight, the average i.v.dose necessary to induce medium depth anaesthesiais about 30 mg/kg. In small pigs there is a considerablemargin of safety, but in larger ones greatvariations in susceptibility may occur. Castratedanimals appear to be slightly more susceptible thanentires. Provided that injection is made slowly andthe onset of muscle relaxation is observed, themethod is safe. Induction is not associated with narcoticexcitement; in fact, in the case of a squealinganimal, the progressive reduction, and finally cessationof squealing, is a good guide to the progress ofnarcosis. Depths of anaesthesia may be difficult toassess in pigs. The presence of complete relaxationof abdominal muscles and absence of response topricking of the skin is usually taken as evidencethat anaesthesia has been attained. Its durationwill be sufficient for the performance of rapid operationssuch as castration. For very large subjectsdoses per kg need to be reduced and marked variationsin susceptibility will be encountered.The duration of surgical plane anaesthesia willdepend upon the initial depth induced. As a rule itis shorter than in dogs. With light levels of unconsciousness– a brisk corneal reflex and a reflexresponse to skin pricking – it is of 10 to 15 minutesonly; when there is a sluggish corneal reflex andloss of reflex response to pricking – 20 to 25 minutes.Anaesthesia is followed by a period of progressivelylightening narcosis which persists for3 to 8hours. Recovery is not accompanied by narcoticexcitement and the animal usually passes into astate of sleep. For non-survival experiments, afterinduction with 30 mg/kg pentobarbital, anaesthesiamay be maintained by continuous i.v. infusionof pentobarbital at about 2 mg/kg/hour althoughthis rate may need adjustment from time to time.In very small, unsedated subjects in whichintravenous injection may be found to be difficult,the intraperitoneal route may be adopted,

378 ANAESTHESIA OF THE SPECIESalthough in general, it is not to be recommended. Itbecomes necessary to compute an anaestheticdose. For animals up to 20 kg this is put at30 mg/kg; for those between 20 and 30 kg, at24 mg/kg. Variations in response are inevitablewith such a method. In some cases narcosis onlywill be obtained and it will be necessary to augmentit by inhalation or local analgesic injection,while in others it may become alarmingly deepand even fatal. Provided a careful watch is kept onthe breathing pattern and IPPV applied shouldrespiration cease, fatalities should, however, be ofrare occurrence. Provided efficient IPPV is usedpigs will survive after some three times the anaestheticdose has been given. In fat subjects there isthe possibility that, despite the length of the needleemployed, the injection will be made intoretroperitoneal fat. In this case absorption will beso slow it is improbable that even light narcosiswill develop. When employing this route ofadministration, the action of the drug will attain itsmaximum depth in a period of 20 to 30 minutesafter injection. The duration of the period of anaesthesiaand of narcosis tends to be rather longerthan with the i.v. method.Intratesticular injection of pentobarbitalA concentrated solution of pentobarbital sodium,such as one commercially available for euthanasiaof small animals (300 mg/ml) may be administeredby intratesticular injection prior to castration. Adose rate of about 45 mg/kg is employed, a verylarge boar being given 20 ml of solution into eachtesticle and adequate anaesthesia for castrationdevelops within 10 minutes of injection. Removalof the testicles removes any excess drug so that toprevent overdosage the testicles must be removedas soon as the boar becomes anaesthetized. Caremust be taken in disposal of the testicles after theirremoval since they still contain enough barbiturateto produce fatal poisoning of any animal (e.g. thefarm dog) which might eat them.SaffanWhen no premedication is used, i.v. doses of6 mg/kg produce surgical anaesthesia of 10 to15minutes duration followed by smooth recovery.In larger pigs intravenous doses of 6 mg/kgconstitute too large a volume for convenience andit is usual to employ premedication to reduce thedose needed. Following sedation with 4 mg/kgazaperone i.m., i.v. injection of 2 mg/kg of Saffanproduces good surgical anaesthesia with adequatemuscle relaxation and minimal respiratory depression.Further increments of Saffan can be given toprolong anaesthesia without appreciable increasein recovery time.KetaminePigs are rapidly immobilized by i.m. injection of20 mg/kg ketamine, which produces adequateanalgesia for the performance of minor operations.Wakening is often abrupt and many pigs seem toremain sensitive to noise throughout the period of‘anaesthesia’. Much better results are obtained by2 to 5 mg i.v. after pretreatment with 1 mg/kgxylazine, although this latter drug seems to produceno obvious sedation in these animals.Reasonably satisfactory results are also obtainedwhen 10 to 18mg/kg of ketamine are given after i.v.injection of 1 to 2 mg/kg of diazepam. Pot-belliedpigs generally need about half these doses.Ketamine (8 mg/kg) and xylazine (2 mg/kgdrawn into the same syringe may be injectedintratesticularly to provide anaesthesia for castrationof large boars. Rapid castration removes theremaining drugs contained in the testicles andrecovery is more rapid than after intratesticularpentobarbital.It must be remembered that ketamine, xylazineand diazepam are all rather expensive for use infarm animals.Triple dripThe combination of ketamine, xylazine andguaiphenesin in 5% dextrose (‘triple drip’) givenby i.v. infusion, although rather expensive, can beused in pigs as in other species of animal to produceand maintain anaesthesia. The solution isusually prepared immediately before use to contain2 mg of ketamine, and 1 mg of xylazine per mlof 5% guaiphenesin. Induction of anaesthesiausually needs 0.6 to 1 ml/kg. Following thismaintenance of anaesthesia is accomplished by

THE PIG 379infusion of approximately 2.2 ml/kg/hour but therate of infusion must, of course, be adjusted toeffect as judged by monitoring the usual signs ofanaesthesia. Recovery usually takes some 30 to 45minutes following cessation of administration butcan be hastened by the cautious i.v. injection ofatipamezole.Inhalation anaesthesiaBreathing systems designed for use in man, andwhich are used for dogs, may be employed for allbut the largest of boars and sows. In the latter, systemsdesigned for equine anaesthesia are moreappropriate.Endotracheal intubation is essential if IPPV is tobe used but otherwise volatile agents may beadministered via a face mask. Large Hall-patternface masks are adequate for small pigs but maskssuitable for large pigs are not commercially available.Fortunately, conical or snout-shaped masksare fairly easy to design and construct andalthough they may not fit tightly around the pig’ssnout a gas-tight seal can be obtained by wrappingwet towels around the edge of the mask. The pigbreathes through the nose, so whatever mask isused it is essential to ensure that it does not blockthe flow of gas into the nostrils. Luckily, the anteriorposition of the nostrils makes their obstructionby the mask much less likely than in animals suchas cattle where the nares are situated more laterally.If a suitable snout mask is not available theanaesthetic may be administered through a Hall’smask placed over the nostrils, although it is obviouslyimpossible to make this a gas-tight fit and aconsiderable quantity of anaesthetic escapes to theatmosphere. Whenever the pig is not intubated thetendency towards respiratory obstruction must beovercome by pushing the mandible forward aspreviously described (Fig. 14.2).Induction of anaesthesia with inhalation agentsis usually free from excitement but, except in smallpigs, it is usually more convenient to induce anaesthesiawith a parenterally administered drug anduse inhalation agents just for maintenance ofanaesthesia. Under farm conditions, when methodsof administration may lead to considerablewastage of anaesthetic, the older, less expensiveagents are usually employed but when moresophisticated apparatus is available any inhalationagent may be used.TrichloroethyleneTrichloroethylene – once quite widely used inporcine practice – is no longer commercially availableas a preparation for inhalation anaesthesia.EtherInhalation of ether by conscious pigs producescopious salivation and bronchial secretion, evenafter atropine premedication, so it cannot beregarded as a satisfactory induction agent for thisspecies of animal. Given by semi-closed or lowflowmethods following suitable premedicationand induction with i.v. agents, it can produce goodanaesthesia with marked muscle relaxation.Non-inflammable inhalation agentsAll modern inhalation anaesthetics are safe anaestheticsfor pigs other than those susceptible tomalignant hyperthermia. Halothane and isofluraneare known to be associated with triggeringthis condition in susceptible animals but in thisrespect the position of enflurane, sevoflurane anddesflurane is currently uncertain, although itseems likely that they too may act as triggers.Because of the need for suitable equipment fortheir safe administration use of all these agents ismore or less confined to hospital conditions. Desfluranerequires a very expensive special vaporizerfor its administration and it is likely that at least forthe foreseeable future its use will be confined toexperimental animals in well equipped laboratories.The physical characteristics of halothane andisoflurane are so similar that they may be administeredfrom the same precision vaporizer designedfor either drug provided that it is carefully cleanedbefore the subsequent use of the other agent.Because of its potency and relative low costwith an absence of toxicity (except in malignanthyperthermia susceptible pigs), halothane is anexcellent anaesthetic for pigs of all ages. Inductionof anaesthesia is rapid and provided the animalcan be effectively restrained there is seldom anyneed to use i.m. or i.v. administration of other drugsfor this purpose before halothane is given.

380 ANAESTHESIA OF THE SPECIESSquealing ceases after as few as 4 or 5 breaths andinhalation of the vapour does not provoke salivationor breath holding. Recovery from anaesthesiais equally smooth and rapid.Isoflurane is similarly effective but tendsto cause more respiratory depression in pigsnot being subjected to surgical stimulation. Unfortunately,the cost of halothane and isofluraneand the need for accurately calibrated vaporizerslimits their use on farms but, where low-flow orsemi-closed methods can be used halothane andisoflurane are worthy of consideration for porcineanaesthesia. Their main disadvantages in pigs, asin all species, are those of cardiovascular depressionleading to hypotension, respiratory depressionand the comparative lack of ability tosuppress motor response to surgical stimulation.Sevoflurane has not been widely used in pigsbut there seems no reason to suppose it will notprove to be an effective anaesthetic agent. It solubilitycharacteristics indicate it should produce arapid induction coupled with prompt recoveryfrom anaesthesia.Desflurane’s solubility in blood is much lessthan that of the other halogenated volatile agentsand thus, induction of anaesthesia and recoveryare rapid, while the depth of anaesthesia is readilycontrollable.Nitrous oxide (N 2 O)It is impossible to induce anaesthesia in pigs withN 2 O but as long as sufficient O 2 is provided it maybe supplemented with a volatile anaesthetic agent.In particular, it can be used to speed induction ofanaesthesia with the halogenated agents (‘secondgas’ effect).The sequence of premedication, induction ofanaesthesia with thiopental sodium, endotrachealintubation under the influence of a neuromuscularblocker and the maintenance of anaesthesia byendotracheal non-rebreathing administration ofN 2 O plus an intravenous or inhalational supplementtogether with a neuromuscular blocker withIPPV has proved to be a very satisfactory methodfor lengthy experimental surgical procedures inpigs of all ages. By this system N 2 O provides valuableanalgesia so that very light anaesthesia can bemaintained while the neuromuscular blockingdrug produces muscle relaxation as needed.Recovery from anaesthesia is rapid and after surgicalprocedures the administration of analgesicsis usually obligatory.NEUROMUSCULAR BLOCKINGAGENTSNeuromuscular blocking agents are used in pigs tofacilitate endotracheal intubation and for thoracic,abdominal, or some experimental procedures. Asin all species of animal, two things are essential ifthese drugs are to be administered:1. The pig must be unconscious and unawareof its surroundings, i.e. anaesthetized with recognizedanaesthetic agents.2. Means to apply efficient IPPV must beavailable.Techniques involving neuromuscular blockers arenot designed for use in the field, and can only beproperly employed to advantage by a skilledanaesthetist. All those intending to use these drugsin porcine anaesthesia should be thoroughly familiarwith the pharmacology (Chapter 7) and withthe methods of IPPV (Chapter 8). By providingcomplete muscular relaxation their use means thatthe surgeon does not need to apply forcible retractionto tissues to gain access to the surgical site andso avoids tissue bruising which can give rise topost-operative pain.SuxamethoniumThe main use of suxamethonium in pigs is tofacilitate endotracheal intubation. Atropine premedicationis essential to counter the autonomicstimulating effect of the initial depolarizing process.Following induction of anaesthesia, doses of2 mg/kg produce complete paralysis of skeletalmuscles for about 2 minutes, i.e. long enough toallow unhurried, atraumatic intubation. It is, ofcourse, necessary to perform IPPV until full spontaneousbreathing is resumed. When non-depolarizingblockers are to be employed for theremainder of the anaesthetic period many anaesthetistsconsider recovery from the suxamethoniumparalysis should be complete before they are administeredbut this does not seem to be essential.

THE PIG 381Table 14.1 Neuromuscular blocking drugs whichhave been used in pigsDrug Dose Approximate(mg/kg) duration ofaction (min)Suxamethonium 2.0 2–3D-tubocurarine 0.3 25–35Gallamine 4.0 15–20Alcuronium 0.1 30–40Pancuronium 0.12 25–30Vecuronium 0.1 15–20Atracurium 0.5 20–60Non-depolarizing neuromuscular blockingagentsAll the non-depolarizing relaxants used in manmay be employed in anaesthetized pigs to facilitatesurgical or experimental procedures. Thechoice of drug depends on the duration of actionneeded, on the route of its elimination, and on thecardiovascular effects it produces. The drugswhich have been used are listed in Table 14.1.The technique most commonly applied is thatas described under N 2 O above. Ventilators designedfor use in adult humans are adequate forthe majority of pigs, but large boars and sows mayhave to be ventilated with one of the ventilatorsdesigned for use in adult horses and cattle. At theend of the procedure it is usual to give atropine (indoses of up to 0.3 mg/kg) or glycopyrrolate (up to0.2 mg/kg) followed by neostigmine (up to 2.5 mgtotal dose) or edrophonium (up to 0.5 mg/kg) torestore adequate spontaneous breathing. In pigsthe depth of neuromuscular blockade is best estimatedby stimulation of the ulnar nerve as in the dogand cat using ‘double-burst’ stimulation.meninges continue, around the phylum terminale,as far as the middle of the sacrum. At the lumbosacralspace the sac is comparatively small, andit is improbable that a needle introduced at thispoint will penetrate into the subarachnoid space.The lumbosacral aperture is large. Its dimensionsin the adult are approximately 1.5 cm craniocaudallyand 3 cm transversely. The depth of the canal isabout 1 cm.The site for insertion of the needle is located asfollows: the cranial border of the ileum on eachside is found with the fingers. A line joining themcrosses the spinous process of the last lumbar vertebra(Fig. 14.11). The needle is inserted in the midlineimmediately behind this spinous process anddirected downwards and backwards at an angle of20° with the vertical. The depth to which the needlemust penetrate in pigs of from 30 to 70 kg willvary from 5 to 9 cm. The landmarks described arereadily detected in animals of smaller size but theymay be entirely masked by the overlying tissues inCrest ofthe ileumLumbosacralspaceLast lumbarvertebraSacrumLOCAL ANALGESIACaudal nerve block is not employed in pigs andepidural block is usually used simply for economicreasons.Epidural blockIn the pig the spinal cord ends at the junction of the5th and 6th lumbar vertebrae and the spinalFIG.14.11 Dorsal view of the pig’s pelvis. A lineconnecting the iliac crests crosses the last lumbarvertebra.The lumbosacral space in adult pigs is 2.5 – 3 cmcaudal to this point.The patella can be used as a reliablelandmark for location of the iliac crest in larger animals;with the hindlegs in a normal standing position,a verticalline through the patella will cross midline on level with thecrest of the ileum.

382 ANAESTHESIA OF THE SPECIESlarger ones. In these a point 15 cm cranial to thebase of the tail serves as a fairly accurate guide.Provided the needle is introduced in approximatelythe correct position and direction, the size of the lumbosacralspace makes its detection comparativelyeasy. Eighteen gauge needles are used; for pigsbetween 30 and 50kg one 8cm long, and for animalsof 70 kg and above, one 12 cm long are required.Before inserting the epidural needle an insensitiveskin weal should be produced. The animal isrestrained either on its breast or side. For smallpigs the latter is preferable, as sudden movementcan be better controlled. In large sows and boarsthe injection is made in the standing animal.Owing to difficulties with restraint, it is generallynecessary to make the injection comparatively rapidly.Penetration of the canal is often associatedwith sudden movement, for which attendantsmust be prepared. Rapid injection seems to causediscomfort, presumably due to transient elevationof CSF pressure. In pigs weighing from 10 to 20 kgthe interarcuate ligament is at a depth of about 2 to3.5 cm from the skin surface while in adult sowsand boars it may be at a depth of up to 15 cm.Epidural analgesia has been used for the castrationof pigs of 40 to 50 kg, injecting 10 ml of 2% lignocainesolution with adrenaline. Completedesensitization of the scrotum, testes and spermaticcord was present in 10 minutes, and there wasa partial motor paralysis of the hind-limbs.Recovery was complete at the end of the secondhour.It is difficult to know up to what weight of animalthis recommendation can be employed, for inlarger animals fat often represents a considerableproportion of body weight. It is suggested that for2% lignocaine the dose should be 1.0 ml per 7.5 kgfor pigs weighing up to 50 kg and an additional1.0ml for every 10 kg above this in weight. Anothersuggestion which has proved to be satisfactory isbased on occiput–tail base measurement allowing1.0 ml for the first 40 cm and an additional 1.5 mlfor each 10 cm longer length. Certainly, whenadministered at the lumbosacral space 20 ml of 2%lignocaine is adequate for caesarian section insows weighing about 300 kg.Recently the effects of xylazine and detomidineinjected at the lumbosacral space have been evaluated(Lumb and Jones, 1996). Epidural xylazine(2mg/kg in 5ml 0.9% saline) induces bilateral analgesiaextending from the anus to the umbilicuswithin 5 minutes after completion of the injectionand persists for at least 10 minutes. Detomidine(500 µg/kg in 5 ml 0.9% saline) induces recumbencybut analgesia caudal to the umbilicus is minimal.In large sows 1 mg/kg of 10% xylazine in10ml of 2% lignocaine injected at the lumbosacralspace produces analgesia extending from the anusto the umbilicus 5 to 8 minutes after completion ofthe injection.Tendillo et al. (1995) found that epiduralxylazine 0.2 mg/kg diluted in saline to 0.5 ml/kgproduced analgesia in isoflurane anaesthetizedhealthy Landrace–Large White pigs for up to90minutes.Analgesia for castrationLocal analgesia is quite suitable for the castrationof male pigs up to about 5 months of age but generalanaesthesia is probably more satisfactory forolder animals.In the field, intratesticular injection is probablythe most practical method of local analgesia. Aneedle of suitable size is thrust perpendicularlythrough the tensed scrotal skin and advanced untilits point lies in the middle of the testicle. Between 3and 15 ml, depending on the size the animal, of 2%lignocaine hydrochloride are injected into the middleof the testicle and a further 2 to 5 ml are injectedsubcutaneously beneath the scrotal skin as the needleis withdrawn. Both sides are treated in thesame manner. Operation may commence about5minutes after completion of the injections.POSTOPERATIVE CAREIt is absolutely essential that pigs should be kept ina warm environment until they are completelymobile after sedation or general anaesthesiabecause, due to their lack of body hair, they areprone to develop hypothermia if left in cold surroundings.Close observation during recovery isnecessary so that immediate measures may betaken to relieve any respiratory obstruction whichmay occur. Postoperative pain relief is essential,particularly following all surgical procedures.Narcotic analgesics may be given as necessary, in

THE PIG 383doses similar to those used in dogs. Amongst thosemost commonly employed are morphine (0.1mg/kgup to a maximum of 20mg for large pigs) and pethidine(2 mg/kg up to a maximum of 1.0 g in largeboars and sows). It is probable that postoperativeanalgesia is frequently considered as being toouneconomic for use after operations such as castrationbut, ethically, veterinarians are obliged to givepain relief whenever desirable without undueregard for agricultural economic considerations.REFERENCESHall, L.W., Woolf, V., Bradley, J.W.P. and Jolly, D.W.(1966) Unusual reaction to suxamethonium chloride.British Medical Journal ii: 1305.Hall, L.W., Trim, C.M. and Woolf, N. (1972) Furtherstudies of porcine malignant hyperthermia. BritishMedical Journal ii: 145–148.Bradley, W.G., Ward, M., Murchison, D., Hall, L.W.and Woolf, N. (1973) Clinical, electrophysiologicaland pathological studies on malignanthyperpyrexia. Proceedings of the Royal Society ofMedicine 66: 67–68.Lumb, W. V. and Jones, E.W. (1996) VeterinaryAnesthesia, 3rd edn. Baltimore: Williams & Wilkins,p. 501.Tendillo, F.J., Pera, A.M., Mascias, A. et al. (1995)Cardiopulmonary and analgesic effects of epidurallidocaine, alfentanil and xylazine in pigs anesthetizedwith isoflurane. Veterinary Surgery 24: 73–77.Woolf, N., Hall, L.W., Thorne, C., Down, M. and Walker,R.G. (1970) Serum creatine-phosphokinase levels inpigs reacting abnormally to halogenated anaesthetics.British Medical Journal iii: 386–387.

Anaesthesia of the dog 15INTRODUCTIONWithin the last 15 years there has been a considerablenumber of changes in the way anaesthesia isconducted in dogs. Introduction of new drugs hasbroadened choices for anaesthetic protocols andenabled use of appropriate combinations to meetdemands of increasingly sophisticated and moreprotracted medical and surgical procedures.Monitoring equipment has become availablespecifically for veterinary medicine and its cost issuch as to make its purchase feasible in generalveterinary practice. Now, more than ever, it is possibleto focus on the individual patient’s problemsand to design anaesthetic management to providesafe anaesthesia with optimum surgical conditionsand minimal adverse impact on postoperativecourse.SEDATION AND ANALGESIASelection of a drug or drugs for sedation dependson the purpose for which it is intended. Mild tranquilizationcan be achieved with a phenothiazinesuch as acepromazine whereas moderate to heavysedation is better obtained using an α 2 agonist,such as medetomidine, or a neuroleptanalgesicmixture, such as morphine with acepromazine.Dose rates chosen may depend on whether theanimal is to be only sedated or whether sedation isto be followed by general anaesthesia. Whenthe drugs are used for premedication to anaesthesia,dose rates are often considerably lower soas to minimize cardiovascular and respiratorydepression.PHENOTHIAZINE DERIVATIVESAcepromazine is the phenothiazine most commonlyused for sedation in dogs. It is best used as a2 mg/ml solution in dogs as dose administrationcan be more accurate than when a stronger solutionis used. The response to acepromazine is notuniform and depends on the animal’s temperament,physical condition, and breed. In general,the giant breeds (e.g. St Bernard and Newfoundland)are exceptionally sensitive to the drugand will become recumbent and reluctant to movefollowing doses of about 0.03 mg/kg. Smallbreeds, in particular the terrier breeds, are muchmore resistant and may not show signs of sedationfollowing even large doses.Dogs of the Boxer breed are renowned for theirliability to ‘faint’ following even small doses ofphenothiazine derivatives (e.g. 0.02 mg/kg of i.m.acepromazine). This response may occur quitesuddenly, with no prior sedation; the animalbecomes flaccid or unconscious and there is severehypotension with bradycardia. Because thisresponse is similar to a vasovagal reactionwhich might be blocked by atropine or glycopyrrolate,the authors suggest that not only shouldminimal doses (0.02 mg/kg) be employed in this385

386 ANAESTHESIA OF THE SPECIESbreed, but also that they should always becombined with anticholinergics even if beinggiven for purposes other than premedicationbefore anaesthesia.The actions of acepromazine are potentiated byhypovolaemia, uraemia, and old age. Thehypotensive effects of the drug can become particularlyserious in the presence of hypovolaemia.Hypotension is best treated by the rapid intravenousinfusion of balanced electrolyte solutionand, if necessary, by infusion of dobutamine.When an opioid has been administered concurrently,partial reversal of the opioid with naloxonemay assist in restoration of blood pressure.The dose rates for acepromazine decreasewith increasing size of the animal; for i.m. administrationin small dogs, 0.05–0.10 mg/kg; for dogs10 to 20 kg, 0.05 mg/kg; for dogs 20 to 40 kg,0.03–0.05 mg/kg: with a maximum dose of 3 mgfor most large dogs, with occasional dogs beinggiven 5 mg acepromazine with an opioid to induceprofound sedation (Table 15.1). These dose ratesare usually adequate for sedation of most animalsand for premedication. They are lower doses thanthose recommended on the product data sheets butincreasing the dosage rarely increases the sedativeeffect. The action of acepromazine is primarilyanxiolytic and may be negligible in aggressivedogs. In general, there will be better sedation andless cardiovascular depression if an opioid is givenconcurrently when more pronounced sedation isrequired.Acepromazine and atropine solutions maybe mixed in the same syringe and injected i.v.(0.03mg/kg acepromazine) but the drug may stilltake up to 20 minutes to produce its full effects.Acepromazine is said by some to be poorly absorbedfrom s.c. sites but has, in fact, been used satisfactorilyby this route in dogs for many years. Oraladministration is much less reliable and the sedativeeffect is greatly influenced by whether the drugis administered with food or on an empty stomach.An advantage to including acepromazinefor premedication is that it provides some protec-TABLE 15.1 Injectable drugs for sedation or premedication in dogsDrug Dose (mg/kg) CommentsAcepromazine 0.05 to 0.20 i.m.,i.v.small dogs Lowest dose for large dogs,max. usually 3 mg,absolute0.05 to 0.10 i.m.,i.v.10–30kg max.5 mg0.03 to 0.10 i.m.,i.v.>30kgAtropine 0.04 i.m.,s.c.;0.02 i.v. AnticholinergicBuprenorphine 0.006 to 0.010 i.m.,i.v. Onset time 30–40 min.Butorphanol 0.2 to 0.4 i.m.,i.v. Premedication0.05 to 0.20 i.m.,i.v. Postoperative analgesiaDiazepam 0.2 to 0.5 i.v. Do not give alone to healthy dogsGlycopyrrolate 0.010 i.m.;0.005 i.v. AnticholinergicMedetomidine 0.02–0.04 i.m. Profound sedation;severely decreases dose of0.01–0.02 i.v. anaesthetic agentsMidazolam 0.1 to 0.2 i.m.,i.v. Do not give alone to healthy dogsMorphine 0.2 to 1.0 i.m.If using i.v.route, Initiates vomitinggive slowly *Naloxone 0.01 to 0.02 i.m.,i.v.,s.c. Opioid antagonistOxymorphone 0.05 to 0.20 i.m.,i.v. Max.initial dose 5 mg;highest dose only for inductionprotocol;initiates vomiting,pantingPethidine 3.0 to 4.0 i.m. Premedication1.0 to 2.0 i.m.If using i.v.route, Postoperative analgesiagive slowly *Xylazine 0.5 to 2.0 i.m.,0.5 to 1.0 i.v. Initiates vomiting* Give slowly over 5min to avoid hypotension.

THE DOG 387tion against catcholamine-induced ventricularirregular rhythms. Acepromazine should be omittedfrom premedication when severe blood loss orhypotension is anticipated during surgery as theperipheral α blockade complicates treatment ofhypotension. Acepromazine decreases the thresholdfor seizures and it is usual to avoid it in dogswith a history of seizures and when myelographyis scheduled.Other phenothiazine derivatives which areused include propionyl promazine, promazine,promethazine, trimeprazine, and chlorpromazine.The side effects produced by them and the provisionsof use are similar to those of acepromazinebut methotrimeprazine, which is used as part ofthe neuroleptanalgesic mixture ‘Small AnimalImmobilon’, is said to have the added advantageof possessing analgesic properties.α 2 ADRENOCEPTOR AGONISTSXylazineXylazine was the first α 2 adrenoceptor agonist tobe widely used in veterinary medicine. Given i.m.to dogs in doses of 1–3 mg/kg it will produce goodsedation and even hypnosis. The drug is classifiedas a sedative/hypnotic and, as might be expected,increasing the dose leads to greater sedation aswell as increased duration of action. Althoughhigh doses will apparently produce unconsciousness(absence of visible response to externalstimuli) this is associated with severe cardiovasculareffects and prolonged recovery, so that highdoses cannot be recommended. An obvious sideeffect in dogs is retching and vomiting as sedationdevelops.In dogs, xylazine often causes a rise in arterialblood pressure (ABP) and dose-related respiratorydepression. Although atropine may be given toprevent bradycardia its effect is variable, and it issometimes ineffective.Even when sedation is not marked, the doses ofinduction agents are greatly reduced after xylazinepremedication. Xylazine slows the circulation, sothere is a long delay between i.v. injection of ananaesthetic drug and its effects becoming apparent:unless due allowance is made for this, i.v.anaesthetic agents will be overdosed.MedetomidineMedetomidine is a potent α 2 adrenoceptor agonistwhich produces a dose-dependent decrease in therelease and turnover of noradrenaline in the centralnervous system which results in sedation,analgesia and bradycardia. In the periphery,medetomidine causes vasoconstriction by activationof postsynaptic receptors in the vascularsmooth muscle. Thus, as with xylazine, there is aninitial increase in ABP due to an increase in systemicvascular resistance. When administered i.m.at doses which produce deep sedation (40 µg/kg)the rise is minimal and ABP rapidly falls to slightlybelow the normal resting level. Following medetomidineadministration dogs often breathe in anirregular manner, periods of up to 45 seconds ofapnoea being followed by several rapid breaths.Although the mucous membranes appear to becyanotic, PaO 2 is only slightly depressed.With equisedative doses of xylazine and medetomidineboth the type of sedation achievedand the side effects of bradycardia, respiratorydepression and mucous membrane colour are similar.Medetomidine provides better sedation andanalgesia than xylazine and has a longer durationof action (Tyner et al., 1997). Vomiting occurs inabout 20% of dogs receiving medetomidine, but ismore frequent and prolonged after xylazine. Bothxylazine and medetomidine decrease gut motility.Medetomidine, at 10 and 20 µg/kg i.v., significantlydecreases serum insulin concentration butplasma glucose concentration remains within thenormal physiologic range (Burton et al., 1997).Medetomidine has a steep dose–response curveand doses should, ideally, be calculated on a bodysurface area basis rather than on bodyweight. Inpractice this means that smaller dogs require relativelyhigher doses than large dogs. Over the risingphase of the dose–response curve sedation andanalgesia are dose-dependent. Although appearingdeeply sedated vicious dogs may still beaggressive and must be handled with care. Old ageincreases the sedative effect of medetomidine andfrequently a dose of 20 µg/kg will have the sameeffect as 40 µg/kg in a younger dog. The effect andduration of medetomidine also depends on theroute of administration, i.v. producing a moreintense sedation of shorter duration than i.m.

388 ANAESTHESIA OF THE SPECIES(England & Clarke, 1989). Injection s.c. of medetomidineresulted in poor absorption and unpredictableeffect. Following i.v. administration dogswill become recumbent in 2 minutes but maximaleffects may take longer to appear. The duration ofanalgesia may be 45 minutes without further drugadministration, and the time to standing will beapproximately 90 minutes. After i.m. injection,recumbency may occur within 6 minutes or take30 minutes and likewise, the time to standing isvariable from 1.5 to 2.0 hours.The drug is also effective when squirted from asyringe into the oral cavity of difficult dogs indoses of 30–80 µg/kg, but in quiet dogs may beadministered carefully under the tongue and dosesof 5–10 µg/kg are very effective by this sublingualroute which avoids a first-pass through the liver. Inthe UK the data sheet for medetomidine recommendsthat impervious gloves be worn whenhandling the drug. Care is necessary to avoidsplashing the drug on to mucous membraneswhen expelling air from syringes.Investigations relating to the use of anticholinergicswith medetomidine have confirmed that incidenceof ventricular arrhythmias is higher whenatropine and medetomidine are administered atthe same time; an effect which is not observedwhen the atropine is given 10 or more minutesbefore the medetomidine. Since hypertension isthe usual mechanism inducing the bradycardia,administration of an anticholinergic agent willexacerbate the hypertension (Alibhai et al., 1996).Thus, use of an anticholinergic is unnecessary oreven contraindicated when medetomidine is to beused only for sedation. However, when medetomidineis to be followed by inhalation anaesthesiathere is a valid argument for anticholinergic administrationfor premedication to avoid a furtherdecrease in cardiac output and blood pressureinduced by vasodilation from the inhalation agent.The use of medetomidine for premedicationgreatly reduces the doses of subsequent anaestheticrequired in a dose-dependent manner, e.g.moderate doses of medetomidine may decreasethe subsequent dose of thiopental to 2 mg/kg. Itssedative and hypnotic effects have been shown tobe synergistic with those of opioids such as butorphanoland fentanyl (England & Clarke, 1989a)and with other anaesthetic agents.RomifidineRomifidine is the most recent α 2 adrenoceptor agonistinvestigated for use as a sedative in dogs.Similarly to the other agents, romifidine, 40 µg/kgand 80 µg/kg, reduced the subsequent inductiondose of thiopental to 6.5 and 4.0 mg/kg, respectively(England & Hammond, 1997).OPIOID ANALGESICSOpioids are widely used to provide analgesia, inand outside the operating room (Table 15.1). Thechoice of opioid for a specific patient will dependon the origin of the noxious stimulus, the requiredduration of analgesia, the need for sedation or not,assessment of the potential impact of adverseeffects on the patient, and the relative cost. Theopiates such as morphine, pethidine (meperidine),hydromorphone, and oxymorphone are effectiveanalgesics for orthopaedic pain whereas the partialagonist, butorphanol appears to be less effective.Buprenorphine has been unpredictable in providingpostoperative analgesia. Nonetheless, in a clinicalstudy comparing preoperative administration ofmorphine and buprenorphine for post-arthrotomyanalgesia effects, both opioids provided adequateanalgesia (Brodbelt et al. 1997). The approximateonset of action after i.m. administration for butorphanoland oxymorphone is 10–15 minutes, forpethidine is 20 minutes, and for morphine andbuprenorphine is 40 minutes. The degree of sedationinduced by opioids depends on the drug, thedose rate, and the individual response. Some sedationis usually obtained with morphine and oxymorphone,although administration of morphineand to a lesser extent oxymorphone to healthydogs can result in excitement (Robinson et al.1988). Pethidine, butorphanol and buprenorphinemay produce little obvious sedation, althoughdose rates of subsequently administered drugs aredecreased. Pethidine and butorphanol have shortdurations of action of 1–2 h, morphine and oxymorphonemay provide analgesia for 3–4 h, andbuprenorphine appears to last 4–6 h. Fentanyl isvery short lived at 20–40 minutes.The opioids are renowned for their respiratorydepressant effects, particularly when used withinhalation anaesthesia. Hypoventilation (hyper-

THE DOG 389carbia) may increase intracranial pressure and bean undesirable feature for dogs with head trauma,intracranial masses, or spinal cord compression.Hypoventilation may result in inadequate uptakeof inhalation agent and an unacceptably lightplane of anaesthesia. Panting may be a feature ofopioid administration, and this occurs more oftenwith pethidine and oxymorphone. Potent shortacting opioids, such as fentanyl, that are injected assupplements during surgery or given as an infusioncause sufficient respiratory depression thatcontrolled ventilation is usually necessary.Dogs frequently vomit during the onset ofaction of morphine, hydromorphone and oxymorphone,and this is not a desirable feature for dogswith cervical instability or gastrointestinal foreignbodies or obstruction. Vomiting is less likely tooccur if the animal is in pain when the drug is administered.Pethidine and morphine cause severehypotension when given rapidly intravenously.The hypotension may be the result of histaminerelease or due to a direct peripheral vasodilation. Ifgiven i.v., these drugs must be given slowly overseveral minutes to avoid severe haemodynamicchanges or they may be best given by other routes.The other drugs may be given by i.v. or i.m. routesdepending on the need for rapidity of action, buti.m. administration tends to produced a more level,prolonged effect. The cardiovascular effects of i.v.administered opioids are greater when the animalis anaesthetized and decreases in cardiac outputand blood pressure should be expected (Martinezet al. 1997). Decreases in cardiovascular functionmay be unexpectedly dramatic when the opioid isgiven for postoperative analgesia to a patient thathas experienced haemorrhage during surgery.The cardiovascular effects of the opioids aregenerally minor but there are some differencesbetween the agents. Morphine, 1 mg/kg, givenslowly over 5 minutes has only minimal effects onsystemic haemodynamics (Priano & Vatner 1981).Similarly, oxymorphone induces minimal cardiovasculardepression in healthy dogs althoughheart rate may decrease (Copland et al. 1987).SEDATIVE/OPIOID COMBINATIONSThe combination of an opioid with a sedative mayaccomplish one of two goals. On the one hand,addition of an opioid will increase the degree ofsedation and analgesia beyond that achieved byuse of the sedative or opioid alone. Conversely, thecombination allows a decrease in dose rate of oneor both the drugs while still achieving satisfactorysedation. Decreased dose rates may result in lessrespiratory or cardiovascular depression, less airwayobstruction in brachycephalic breeds, and lessdrug to be metabolized for recovery. Furthermore,at the end of the procedure the opioid componentcan be antagonized by injection of naloxone.Sedative-opioid combinations (neuroleptanalgesia)are used for procedures such as radiography,examinations, bandage changes and minororthopaedic manipulations, and for preanaestheticmedication. For some of these combinations dogsremain sensitive to sound and may rouse abruptlyin response to a loud noise or sudden movement.Combinations such as acepromazine, 0.05 mg/kg, with morphine, 0.5–1.0 mg/kg, or oxymorphone,0.05–0.1 mg/kg (5 mg maximum initialtotal dose), or the combination of medetomidine,0.03–0.04 mg/kg, with butorphanol, 0.2 mg/kg,given i.m. will induce profound sedation. Thecombinations of acepromazine, 0.05 mg/kg,with pethidine, 3–4 mg/kg, or butorphanol,0.2–0.4 mg/kg, or buprenorphine, 0.01 mg/kg,cause mild to moderate sedation. The route ofadministration will influence the intensity of sedation.The combination of a benzodiazepine withbutorphanol is useful in brachycephalic dogs withlow risk for causing airway obstruction. For example,administration of butorphanol, 0.2–0.3 mg/kg,with midazolam, 0.2 mg/kg, i.m. to a Bulldogmight induce mild sedation but butorphanol,0.2 mg/kg, with diazepam, 0.2 mg/kg, given i.v.may produce greater sedation and a tractableanimal in lateral recumbency for a short time.Many combinations with different dose ratesare used. Other opioids used include methadone,0.1 mg/kg, and hydromorphone, 0.1–0.2 mg/kg.Omnopon-Scopolamine is a commercially availablemixture and 20 mg Omnopon (papaveretum)and 0.4 mg Scopolamine (hyoscine, an anticholinergic)combined with 3 mg of acepromazine providesgood sedation in aggressive GermanShepherd dogs.Various premixed combinations of drugs aremarketed for sedation in dogs. Hypnorm consists

390 ANAESTHESIA OF THE SPECIESof fentanyl with fluanisone. Intramuscular injectionproduces deep sedation and analgesia ofabout 20 minutes duration, which is suitable forminor surgical procedures. Dogs sedated with thiscombination will move in response to noise.Small Animal Immobilon contains the powerfuland long-acting opioid etorphine in combinationwith methotrimeprazine. Given at the manufacturer’srecommended doses to the dog by the i.v.,i.m. or s.c. routes, it produces a profound and prolongedstate of unconsciousness and analgesia.Intramuscular and s.c. injections are painful.Respiratory depression can be severe and the dogmay appear cyanotic. Convulsions following theuse of Immobilon have been reported to theAssociation of Veterinary Anaesthetists Committeeconcerned with deaths and adverse reactionsof drugs used in anaesthesia.At the end of surgery, the etorphine componentof the mixture may be antagonized by the injectionof diprenorphine but the patient remains sedatedfrom the effects of methotrimeprazine. It must beremembered that once the antagonist has beengiven, attempts to provide analgesia with pureagonist opioids will be unsuccessful. Followingreversal dogs tend to return to a state of deep sedation,or even unconsciousness, several hours afterthe antagonist has been given. Instances of postsedation renal failure have occurred after theuse of Immobilon which could be a result ofhypoxia and/or hypotension during the period ofsedation.Owners have reported that dogs `appear to bedifferent’ after Immobilon. Behavioral changes,including aggression to people within or outsidethe family have been reported after sedation withacepromazine-oxymorphone (4% of dogs) or fentanyl-droperidol(15% of dogs) (Dohoo et al. 1986).BENZODIAZEPINESDiazepam or midazolam are not often administeredalone to healthy dogs as they may induceexcitability. They are frequently used in combinationwith an opioid for sedation or preanaestheticmedication and within the combination contributeto greater sedation than would be obtained by theopioid alone. Diazepam or midazolam are ofteninjected i.v. just before thiopental, methohexital, orpropofol and will produce a small decrease in thedose rate needed for induction of anaesthesia.These benzodiazepines are often included withketamine to prevent the central nervous systemexcitation that may be caused by ketamine.Diazepam is poorly absorbed from i.m. injection.Midazolam is a water-soluble benzodiazepinethat is twice as potent as diazepam and isbetter suited for i.m. administration. Midazolam,unlike diazepam, is not painful on i.v. injectionand does not cause thrombophlebitis. Both agentsare commonly used because of their cardiovascular-sparingaction. They cause minor changes incardiac output and mean arterial pressure atthe dose rates used clinically (Jones et al. 1979).Heart rates may be increased and this mayhave an adverse influence in dogs with ventriculardysrhythmias. Diazepam is commonlygiven i.v. at a dose rate of 0.2–0.25 mg/kg but thismay be increased to 0.5 mg/kg in some circumstances.Midazolam is administered i.m. or i.v. at0.1–0.2 mg/kg.Temazepam does not form active metabolitesand has a relatively short duration of action. It maybe given to dogs in a soft gelatine capsule in dosesof approximately 0.25 mg/kg. Zolazepam is availablein a fixed combination with the dissociativeanaesthetic, tiletamine.Flumazenil is a benzodiazepine antagonist thatbinds competitively, reversibly, and specifically tothe same central nervous system sites as benzodiazepines.Agonist-antagonist ratios of flumazenilto rapidly and completely reverse the effects ofdiazepam and midazolam overdose in dogs is 26:1for diazepam and 13:1 for midazolam (Tranquilliet al. 1992).NON-STEROIDAL ANTI-INFLAMMATORYDRUGSNon-steroidal anti-inflammatory drugs (NSAIDs)are frequently used for pain relief in animalsbefore anaesthesia and surgery and can be used tosupplement analgesia in the postoperative period.NSAIDs used in dogs include aspirin, phenylbutazone,naproxen, meloxicam, ketoprofen, carprofen,and etodolac. Adverse side effects includegastritis, gastrointestinal haemorrhage, hepatocellulartoxicosis, and acute renal failure (Johnston &

THE DOG 391Fox, 1997; MacPhail et al., 1998). Gastroduodenallesions were observed by endoscopy in 71% ofhealthy dogs receiving carprofen, meloxicam, orketoprofen for 28 days, although none of the dogshad clinical signs related to the lesions (Forsyth etal., 1998). There is some evidence that the prevalenceand severity of adverse side effects are lesswith carprofen. Dogs undergoing anaesthesia andsurgery might be imagined to be at greater risk ofadverse effects from NSAIDs because these proceduresmay produce disturbances of fluid balanceand decreased organ blood flow which will slowelimination and result in prolonged blood concentrationsof NSAIDs. However, fluid balance disturbancesare usually corrected at the time of surgeryand for analgesia it is seldom necessary to administerthese drugs for more than the first 48 postoperativehours.A prospective evaluation of carprofen administeredat 4 mg/kg preoperatively for a variety oforthopaedic procedures indicated that dogs givencarprofen had similar or slightly better pain scoresthan dogs given pethidine pre- and postoperatively(Lascelles et al., 1994). A later study of theefficiacy of carprofen for analgesia in dogs undergoingovariohysterectomy confirmed that carprofenprovided pain relief and suggested thatadministration of carprofen preoperatively hadadvantages over postoperative administration(Lascelles et al., 1998). Immediately after anaesthesiafor elective orthopaedic surgery, trials showedthat evidence of pain relief was present 4 hourslater in dogs given ketoprofen but not in dogsgiven oxymorphone alone (Pibarot et al., 1997).PREPARATION FOR ANAESTHESIAPreparation for anaesthesia includes preanaestheticevaluation of the ability of the patient towithstand the changes induced by general anaesthesiaand of the potential impact of surgery andanaesthesia on the intra- and postoperative course.Choice of anaesthetic agents and management isbased on information derived from the dog’s history,physical examination, abnormal valuesdetected by laboratory tests, nature of any currentillness, and requirements of the proposed medicalor surgical procedure. The significance of manyof the conditions which may be discovered duringpreanaesthetic evaluation are discussed inChapter 1 and later on in this chapter.There are, however, some aspects of the preanaestheticpreparation of dogs that deal withroutine management and warrant further considerationhere.CONCURRENT DRUG THERAPYPrevious drug therapy can alter the response ofdogs to anaesthesia and operation so it is essentialthat details of drug use should be sought from thecase history. A full discussion of all possible druginteractions is beyond the scope of this book andreference should be made to textbooks on pharmacologyand drug interactions. Interactions that areencountered fairly commonly in canine anaesthesiaare described below.1. AntibioticsChloramphenicol increases the length of action ofbarbiturate and inhalant agents but this rarelypresents a clinical problem. More importantly,antibiotics given rapidly i.v. during anaesthesiacan, in some dogs, induce profound hypotensionthat is unresponsive to treatment (Table 15.2).Antibiotics to be administered i.v. should be givenslowly over several minutes with a close watch foreffect on the ABP, particularly in dogs with cardiovascularinstability. Many antibiotics, includingthe streptomycin group, the polymixins, and tetracyclines,exert an influence at the neuromuscularjunction which enhances the effects of non-depolarizingmuscle relaxants. This may induce re-paralysiswhen these antibiotics are administered at theend of anaesthesia.2. CorticosteroidsDogs which have been treated with corticosteroiddrugs at any time in the two months precedinganaesthesia may have reduced ability torespond to stress. Additional steroid cover maybe advisable in the form of methylprednisolonesodium succinate, 10 to 20 mg/kg i.v., or dexamethasone,0.5–2.0 mg/kg, or another steroid moreappropriate for the individual dog’s condition

392 ANAESTHESIA OF THE SPECIESTABLE 15.2 Impact of concurrent administrationof drugs on anaesthetic managementDrugSignificanceAntibioticsCarbonicanhydraseinhibitorsCardiovasculardrugsCorticosteroidsDiureticsInsulinNon-steroidalanti-inflammatorydrugsOrganophosphateanthelminticPhenobarbitalIntravenous administrationduring anaesthesia causesmoderate,occasionally severe,decrease in blood pressure insome dogs. Aminoglycosideantibiotics can cause muscleweakness and potentiateneuromuscular block fromnon-depolarizing relaxants.Chloramphenicol prolongssleep time with ketamine andinhalant agents.Induce metabolic acidosisCalcium channel blockers andACE inhibitors may contributeto hypotension duringanaesthesia unresponsive totreatment with vasoactivedrugsLong term preoperative usemay predispose to circulatorycollapseFrusemide (furosemide)decreases serum potassiumand may cause muscleweakness and cardiacarrhythmiasRisk of hypoglycaemia duringand after anaesthesiaAnaesthesia increases risk fortoxic effects;May beprevented byadequate fluid therapyIncreases toxicity ofacepromazine;may decreaseanaesthetic requirement;prolongs duration of action ofsuxamethoniumChronic use for seizurecontrol associated withdecreased hepatic function.Hepatic enzyme induction mayincrease production ofmetabolites from halothane totoxic levelbased on knowledge of the history and previousdosing regime. Further steroid may be neededdepending on the severity of the surgicalprocedure and how the dog recovered fromanaesthesia.3. BarbituratesLong term barbiturate therapy for epilepsy willlead to enzyme induction and a decrease in durationof action of similar drugs given for anaesthesia.Administration for years leads to hepaticcirrhosis and decreased hepatic function. Theeffects of acutely administered phenobarbital orpentobarbital for the seizuring animal will beadditive to subsequently administered drugs foranaesthesia for collection of cerebrospinal fluid orfurther diagnostic tests.4. Other drugsThe number of dogs on cardiac medications hasincreased in recent years. Calcium channel blockingagents, such as verapamil and diltiazem, maybe used to treat dogs with supraventricular tachyarrhythmias.Atrial fibrillation or flutter in dogswith dilated cardiomyopathy or advanced mitralregurgitation may be treated with these drugs,which slow conduction through and prolong therefractory period of the atrioventricular node(Pion & Brown, 1995). The cardiovascular effects ofanaesthetic agents may be greater in dogs receivingthese drugs. Anaesthesia with halothane orisoflurane may be associated with hypotensionand episodes of sinus arrest (Priebe & Skarvan,1987; Atlee et al., 1990). Treatment with atropinemay be necessary to increase sinus rate and atrioventricularconduction. Benzodiazepines maycompete for serum binding sites thus increasingfree serum levels of verapamil. Lignocaine administrationto dogs receiving verapamil results in achange in distribution of verapamil unrelatedto protein binding but fortunately has minimalimpact on cardiac function (Chelly et al., 1987).In contrast, the combined administration of -verapamil and bupivacaine leads to decreasedmyocardial contractility and to high-grade atrioventricularblocks in conscious dogs. Diltiazemhas been found to potentiate the neuromuscularblockade by vecuronium in humans (Takasakiet al., 1995).

THE DOG 393TABLE 15.3 A protocol for anaestheticmanagement of a regulated diabetic dogSequence of events ManagementNight before surgery Feed as usualMorning of the day Give one-half of the usualof surgerydose of insulin;do not feedBefore anaesthesia Measure blood glucose;administer dextrose if valueis lowDuring anaesthesia Administer 5% dextrose inwater,3 to 5 ml/kg/h,inaddition to balancedelectrolyte solution;measureblood glucose at the end ofanaesthesia,or every 1–2hours,and adjust dextroseinfusion rate according toresultAfter anaesthesia Measure blood glucose 2hours after anaesthesia;adjust treatment accordingto result;feed and return toinsulin therapy as soon asappropriateBREED CHARACTERISTICSThe breed, age, and conformation have significantimpact on choice of drugs and anticipated complications.Breed predispositions for different diseasesand traits are extensive and appear to beconstantly changing (Buchanan, 1993). Variableresponses to anaesthetic drugs within breeds havealso been reported. Some families of the Boxerbreed, for example, are very sensitive to the effectsof acepromazine. Several other breeds have beensuggested as having increased sensitivity to anaestheticagents, for example, the Belgian Terveuransand the Siberian Husky, and there is no doubt thatoften an adult St Bernard requires less drug foranaesthesia than an adult Great Dane. It is verylikely, and this hypothesis is supported by experienceand anecdotal reports, that there are strains ofdogs within many breeds that have a very low tolerancefor anaesthetic agents. Consequently, safetyis increased when balanced anaesthetic techniquesare employed and drugs are administered sequentiallyand ‘to effect’.Angiotensin-converting enzyme (ACE) inhibitors,such as captopril and enalapril, are currentlyused in the treatment of dogs showing clinicalsigns of congestive heart failure. These drugscause vasodilation by blocking the formation ofangiotensin II and subsequent administration ofanaesthetics that cause vasodilation is oftenaccompanied by profound hypotension. Omittingthe dose of drug on the morning of anaesthesiaresults in fewer treated dogs developing hypotensionduring anaesthesia.Diabetic dogs receiving insulin are at risk ofdeveloping hypoglycaemia, hypotension and cerebraldamage during anaesthesia. An acceptedmanagement for the diabetic dog that must beanaesthetized is given in Table 15.3. The bloodglucose level should be maintained between5.5–11.0 mmol/l (100–200 mg/dl) through frequentmeasurement of blood glucose concentrations andappropriate i.v. administration of 5% dextrose inwater. Even dogs with well controlled diabetes canexperience wide swings in blood glucose for severalhours after anaesthesia, and monitoring shouldbe continued until the following day.Brachycephalic breedsConformation will have an impact on anaestheticmanagement. Brachycephalic breeds such asthe English bulldog, Pug, Boston Terrier, andPekingese are at risk of airway obstruction becauseof elongated soft palates, abnormal narrowing ofthe larynx, and everted laryngeal ventricles.Prolonged inspiratory stridor contributes to formationof oedema of the soft palate and laryngealmucosa and tenacious stringy saliva in theoropharynx. These dogs are also more likely todevelop cyanosis during induction of anaesthesiaand to vomit in the recovery period. Obstructioncan occur even during sedation and these dogsshould be kept under observation after administrationof premedicant drugs. Tracheal intubationis more difficult in these breeds and may involvesmaller endotracheal tubes than expected basedon the body size. The anatomy of the EnglishBulldog larynx may be distorted such that only anextremely small lumen tube can be inserted.‘Preoxygenation’ is advisable to prevent hypoxaemiaduring induction of anaesthesia and is accomplishedby administration of O 2 by facemask

394 ANAESTHESIA OF THE SPECIESfor several minutes before and during induction.Acepromazine should be used cautiously, if at all,and propofol or ketamine are less likely to be associatedwith prolonged difficulty in breathing thanthiopental during recovery from anaesthesia.Opioids are useful agents to provide sedation andanalgesia and to decrease the dose of subsequentanaesthetics. One problem with this group is thatBulldogs, Boston Terriers, and Pugs frequentlypant during inhalation anaesthesia.SighthoundsThe lean athletic breeds collectively known as‘sighthounds’ include Greyhounds, Afghans,Salukis, Borzois, Whippets, Wolfhounds andDeerhounds. Their significance to the anaesthetistis the prolonged recovery from anaesthesia inducedby thiopental because of lack of body fat (andmuscle in some breeds), which precludes redistributionand lowering of blood thiopental concentrations.For these dogs, propofol yields vastlyimproved quality of recovery from anaesthesia.Ketamine is a less satisfactory agent for anaesthesiain these breeds than propofol, unless adequatesedation is provided for recovery, because theymay exhibit signs suggestive of dysphoria.AGE CHARACTERISTICSPaediatric anaesthesiaExtremes of age have a significant impact onanaesthetic management (Fig. 15.1). Puppies lessAnaestheticrequirementVentilationBlood pressureRecoveryHypothermiaHypoglycaemiaEffect of age on anaesthesiaPaediatricGeriatricFIG.15.1 Anaesthetic considerations for paediatric andgeriatric animals.than three months of age are more likely to requiresmall doses of anaesthetic agents and to develophypoventilation, hypotension, and hypothermiathan young adults: O 2 consumption is higherin puppies than in mature animals and respiratoryrates are high. Heart rates of around 200beats/min occur in new-born puppies. Decreasedheart rate and decreased preload (blood volume)result in large decreases in cardiac output (Baum &Palmisano, 1997). A small blood loss will cause agreater decrease in cardiac output than in an animal3 months of age. The MAP is considerablylower in the first month of life than in mature dogsand the problem for the anaesthetist is how low istoo low for blood pressure during anaesthesia?MAP of 50–60 mmHg may be satisfactory duringanaesthesia in the first two weeks of life providedthat peripheral perfusion appears to be adequateas indicated by pink membranes and rapid capillaryrefill time. Treatment of low pressure can be aproblem as the immature heart may not respondsatisfactorily to administration of anticholinergicsand inotropic agents. The young animal is capableof a significant increase in cardiac output inresponse to a volume load, but this increase isdepressed in the first few weeks of life.Puppies have a decreased requirement foranaesthetic agents and also immature mechanismsfor detoxification. Renal function does not, forexample, reach adult function until puppies are3months of age (Poffenbarger et al., 1990). Hypoglycaemiamay develop during and after anaesthesia.Food should not be withheld for more than afew hours before anaesthesia and the puppyshould be fed a few hours after anaesthesia. Asprevention against hypoglycaemia, 5% dextrose inwater, 3 to 5 ml/kg/h, should be infused intravenouslyduring anaesthesia in addition to balancedelectrolyte solution. Hypothermia developseasily in these small patients and will have a significanteffect in decreasing ABP and metabolicrate, thus prolonging recovery from anaesthesia.Geriatric (senior) dogsOlder dogs have a decreased requirement foranaesthetic agents due to a reduction in the numberof neurons and neurotransmitter and, becausehepatic and renal function are decreased, the dura-

THE DOG 395Dog A = healthyFATMUSCLEBLOODtion of action of drugs may be increased resultingin longer recovery from anaesthesia. The prevalenceof hypoventilation is higher in senior dogsbecause chemoreceptor response to high PCO 2and low PO 2 is decreased. Hypotension is morelikely to develop due to decreased autonomicfunction with increasing age. Thermoregulation isincreasingly impaired and hypothermia developsas a consequence. Pharyngeal and laryngeal reflexesare diminished and aspiration of reflux is morelikely to occur than in a younger animal.OTHER CONSIDERATIONSOverweight (obese) dogsAnaesthetic drug dosages for an obese dog shouldbe calculated on its ideal weight since the animal’scirculating blood volume is that of a smaller animaland fat contributes little to initial redistribution(Fig. 15.2). Hypoventilation may be severeand controlled ventilation will probably be necessary.An obese animal must not be allowed tobreathe only air when anaesthetized as this willresult in hypoxaemia.Auscultation of the thoraxDog B = overweightAdministration of the same mg/kg dosein overweight dog = overdosageFATMUSCLEBLOODFIG.15.2 Schematic representation of the risk foroverdosage of overweight dogs with intravenousanaesthetic agents.Auscultation of the heart, cardiac rhythm and lungsounds before anaesthesia is essential to identifyabnormalities in animals that exhibit no signs ofdisease to the owner, for example patent ductusarteriosus in the young animal scheduled for castrationor ovariohysterectomy. Auscultation ofmurmurs or abnormal rhythms should be followedup as potential early indicators of cardiomyopathy(Brownlie, 1991). All dogs that havebeen injured in a road traffic accident should beauscultated for decreased lung sounds indicatinglung collapse, pneumothorax, or diaphragmatichernia. Abnormal ventricular rhythm in thesedogs is an indication of traumatic myocarditis,although this clinical sign may not become apparentuntil 24 or 36 hours after the trauma. A thoracicradiograph provides valuable information on theintegrity of the lungs and diaphragm, and thisevaluation is especially important as up to 50% ofdogs involved in automobile trauma will havepulmonary contusions.Preanaesthetic blood testsConsiderable controversy arises concerning bloodtesting of healthy dogs scheduled for elective surgery.Retrospective studies of the outcomes ofanaesthesia of human patients have revealed thatin only a very small number of patients are thereabnormalities shown by laboratory tests whichhave an impact on anaesthetic protocol (Pasternak,1996). In a study of 2000 patients, only 0.22% oftests demonstrated abnormalities that might influenceperioperative management (Kaplan et al.,1985) and in another study of 1010 patients involvingover 5000 tests, important abnormalities werefound relating to only 4 patients (Turnbull & Buck,1987). Nonetheless, identification of only a fewdogs requiring special consideration for anaesthesiamay be justification enough for an evaluationincluding blood tests. There is a rationale for submittingolder dogs to blood testing before anaesthesiaeven when they are thought to be healthy.With increasing age, hepatocyte numbers decrease,pancreatic enzyme secretion diminishes,nephrons decrease, and glomerular filtration ratedecreases (Hoskins, 1995). The age at which a dogshould be considered geriatric (senior) varies withthe breed, but may be said to be 9 years old forsmall and medium dogs, and 6 years for giantbreeds. Many veterinary anaesthetists require thatall dogs over 4 or 5 years of age have blood drawnfor a complete blood count (CBC), plasma protein,blood urea nitrogen and creatinine, liver enzymetests such as alkaline phosphatase (ALP), alanineaminotransferease (ALT) and aspartate aminotransferase(AST), the in vitro levamisole inhibition

396 ANAESTHESIA OF THE SPECIEStest as a screening test for increased serum ALPactivity, and glucose. Measurement of electrolytesmay also be advisable.In the UK many veterinary anaesthetists considerthat dogs should be blood tested only when,based on the history or physical examination thereis an expectation of finding an abnormality, orwhen the dog is in a high risk population. Thismay include expanding the list of tests to cover aparticular concern, for example, tests for coagulopathyin a Doberman pinscher that may sufferfrom von Willebrand’s disease. Further, patientsscheduled for major surgical procedures that aremoderately to severely invasive and carry the riskof major blood loss should have blood tests performedto provide baseline values in anticipationof significant changes from surgery. Abnormalitiesof the results of laboratory tests should be notedfor the possible modification of the anaestheticprotocol, e.g. the impact of low plasma protein inaltering the amount of free and active anaestheticdrug, or in the ability of the dog to maintain anadequate blood pressure. Abnormalities of hepaticor renal function may dictate an adjustment in theselection of anaesthetic agents based on the dog’sdecreased ability to eliminate the drugs. Dogs with30% or less of the normal level of von Willebrandfactor tend to bleed and should be treated with8–D-arginine vasopressin (DDAVP) or an infusionof fresh plasma or cryoprecipitate before anaesthesiaand surgery.It must always be remembered that almost alllaboratory tests are costly to perform and theowner is entitled to have these costs justifiedbefore they can be expected to agree to procedureswhich may or may not influence the outcome oftheir dog’s treatment.Evaluation of the significance of diseaseIdentification of neurological or cardiac disease, orhepatic or renal malfunction, may have a directbearing on choice of anaesthetic agents or anaestheticmanagement as discussed later in this chapter.Some diseases cause derangements of fluid,electrolyte, and metabolic balance and these shouldbe corrected if possible before induction of anaesthesia.Correction of dehydration may not be feasible,but restoration of an adequate circulatory bloodvolume should be ensured by infusion of crystalloid,plasma or plasma substitute, or blood. The impactof the procedure on anaesthesia should beconsidered, for example, surgical procedures in thecranial abdomen or performed with the animal in aprone, head-down position will impair ventilation.Orthopaedic procedures require profound analgesiaand may be responsible for considerable bloodloss. Excision of tumours over the thorax mayresult in penetration of the pleural cavity. Animalswith mast cell tumours should be pretreated withan antihistamine such as diphenhydramine, 2mg/kg. Anaesthesia for thoracotomy or caesariansection is discussed in detail elsewhere.Food and water restrictionsDogs often vomit during induction or recoveryfrom anaesthesia when their stomachs are notempty. Subsequent inhalation of vomit leads toaspiration pneumonia which is frequently fatal. Itis usual practice to withhold food from maturedogs for about 12 hours, and water for at least2 hours, to ensure that a dog will have an emptystomach. Fasting must last at least 16 to 18 hoursfor dogs eating dry food to ensure a completelyempty stomach (Arnbjerg, 1992). A dog that hasbeen involved in a fight or an accident and parturientbitches may have food in the stomach and theanaesthetic technique should be chosen to includea rapid sequence of induction to tracheal intubation.Protective phayngeal and laryngeal reflexesmay not be present for several hours after anaesthesiaand may not be present when a dog firstregains its feet.PREMEDICATIONPremedication in the dog usually involves administrationof anticholinergic, sedative, and opioiddrugs, the combination chosen depending on thecircumstances and anaesthetic technique which isto follow.ANTICHOLINERGICSAnticholinergics are administered to limit bradycardiaand to prevent salivation that might

THE DOG 397obstruct the airway or initiate laryngospasm.Anticholinergics decrease intestinal motility andthe benefit observed is less vomiting in the recoveryperiod. Glycopyrrolate decreases gastricacidity and may protect against oesophageal irritationin the case of reflux. Glycopyrrolate results ina smaller increase in heart rate after intramuscularadministration than atropine and may be preferablein dogs in which high heart rates may haveadverse effects, e.g. geriatric dogs and dogs withmyocardial contusions. Atropine may be contraindicatedin some animals with cardiac disease asthe tachycardia induced may decrease cardiac output,increase the prevalence of ventricular arrhythmias,and increase myocardial ischaemia byincreasing O 2 demand. A further contraindicationto atropine administration is in dogs with a rectaltemperature exceeding 39.7 ° C (103.5 ° F).Atropine sulphate may be given i.m., s.c. or i.v.Dose rates commonly used for premedication are0.04 mg/kg of a 0.5 mg/ml solution s.c. or i.m., orhalf that dose i.v. Onset of action occurs in about20 minutes after i.m. injection and lasts about1.5hours. Onset of action is within 2 minutes afteri.v. injection and the effects on the heart last about30minutes. Higher doses may be used where neededand in the antagonism of neuromuscular block andin cardiopulmonary resuscitation. Glycopyrrolateis given at 0.01 mg/kg i.m. and 0.005 mg/kg i.v.Onset of action after i.m. administration is 40 minutesand duration is 2 to 4 hours.Other anticholinergics are sometimes used aspart of neuroleptanalgesic mixtures. Hyoscine iscombined with papaveretum in Omnopon/ Scopolamineand when this combination is usedatropine is not required.SEDATIVE AND ANALGESICPREMEDICATIONAny of the analgesic and sedative drugs alreadydiscussed may be used for premedication but inTABLE 15.4 Drug combinations for anaesthesia with injectable agents*Premedication Dose rate (mg/kg i.m.) Induction Dose rate (mg/kg i.v.)Acepromazine 0.03 (large dog) Thiopental 120.10 (small dog)Acepromazine 0.03 to 0.10 Thiopental 10Pethidine 3 to 4Acepromazine 0.03 to 0.10 Thiopental 10Butorphanol 0.3 to 0.4Acepromazine 0.03 to 0.05 Thiopental 4 to 6Morphine 0.5Medetomidine 0.02 Thiopental 1 to 3None Propofol 6 to 8Acepromazine 0.03 to 0.05 Propofol 4 to 5Acepromazine 0.03 to 0.05 Propofol 3 to 4Butorphanol 0.2 to 0.3Acepromazine 0.03 to 0.05 Propofol 1 to 2Morphine 0.5Medetomidine 0.04 Propofol 1.0 to 1.5None or acepromazine Diazepam (5 mg/ml) 0.25or butorphanol or Ketamine (100 mg/ml) 5.0 (=1 ml/10 kg using abuprenorphine50:50 mixture)Butorphanol 0.3 Etomidate 0.75 to 1.50None Diazepam 0.2Oxymorphone 0.1 to 0.2* The examples in this table refer to fit healthy dogs.Sick animals may require considerably less while individual dogs may requiremore or less of the induction agent following premedication.

398 ANAESTHESIA OF THE SPECIESdogs those most commonly employed for this purposein are the opioids, the phenothiazines, andthe α 2 adrenoceptor agonists (Table 15.4). Opioidswill provide analgesia during and after the procedureand when administered with sedatives, willincrease the sedation achieved. The choice of agentwill depend partly on the dog and the reason foruse and partly on availability and cost. When vomitingafter premedication is not advisable, such asin dogs with neck pain, gastric or intestinal foreignbodies, decreased ability to protect the airwayagainst aspiration, or with a ruptured cornea, premedicationwith morphine, oxymorphone, andpethidine should be avoided. Similarly, theseagents induce pupillary constriction in dogs andshould not be included in protocols for intraocularsurgery.When analgesia is to be supplemented by use ofa fentanyl patch or epidural morphine, then use ofa partial agonist such as butorphanol for premedicationis not advisable as it will decrease the effectivenessof fentanyl or morphine. Opiates that areµ receptor agonists can effectively be used concurrently,such as morphine or oxymorphone for premedicationfollowed by supplementation with i.v.fentanyl during surgery. In the event that butorphanolhas been used for premedication and later,during anaesthesia, greater analgesia is required, ahigher dose rate of a µ agonist opioid may be necessaryif the time elapsed since the initial administrationof butorphanol is less than 1.5 hours. Onepotential use for mixing µ agonists and partial agonistsis when an agonist such as morphine or oxymorphonehas been used intraoperatively andbutorphanol is used postoperatively. The butorphanolwill reverse the effects of the previous drugbut provide some analgesia with minimal sedationthrough κ receptors (Dyson et al., 1990).Neuroleptanalgesia created by concurrentadministration of a sedative and an opioid is apopular choice for premedication. Sedation ismuch improved by the combination and may dramaticallydecrease the dose rate of drugs used forinduction and to enable endotracheal intubation tobe carried out. The degree of sedation depends onthe drugs used and dose rates, and there is someindividual variation. Intramuscular administrationof butorphanol, 0.2–0.4 mg/kg, buprenorphine,0.01 mg/kg, or pethidine, 3–4 mg/kg, alonemay induce very little sedation but when combinedwith acepromazine, 0.02–0.03 mg/kg theycan produce heavier sedation. Sedation is greaterfrom morphine, 0.3–0.5 mg/kg, oxymorphone,0.07–0.1 mg/kg, or hydromorphone 0.2 mg/kg,but these agents induce profound sedation whencombined with acepromazine and may decreasethe induction dose of thiopental to 3–4 mg/kg.Acepromazine alone in i.v. or i.m. doses of0.02–0.03 mg/kg calms most animals effectivelyfor venepuncture and reduces the induction doseof thiopental or propofol. Active dogs may not besufficiently sedated and here the addition of anopioid is advisable. Larger doses of acepromazinedo not increase sedation but can result in hypotensionduring anaesthesia. Acepromazine contributesto maintenance of a steady plane ofanaesthesia and to a smooth recovery from anaesthesia,while also reducing myocardial irritability.Xylazine and medetomidine produce profoundsedation and greatly reduce the dose of anaestheticsused subsequently. Moderate doses of medetomidine,10–20 µg/kg, administered with an opioidproduce deep sedation that needs only a little ofthe induction drug for intubation to be possible.Care must be taken during induction of anaesthesiasince these drugs slow circulation time, andsufficient time must be allowed to elapse for fulleffect to be shown before administering more ofthe drug. Medetomidine, 30–40 µg/kg, given i.m.with butorphanol, 0.2 mg/kg, produces such deepsedation that endotracheal intubation may beaccomplished without further drug administration.The cardiovascular effects of this group ofdrugs are significant and their use in dogs sufferingfrom cardiovascular disease or those withhypovolaemia is inadvisable.INTRAVENOUS ANAESTHESIAIn dogs, as in other animals, intravenous agentsmay be used either to induce anaesthesia which isthen maintained by inhalation methods, or as soleanaesthetic agents. The use of intravenous drugsas sole anaesthetics does not mean that anaestheticmachines are unnecessary. The i.v. agents commonlyproduce respiratory depression and endotrachealintubation, administration of oxygen and

THE DOG 399even controlled ventilation may be necessary ifhypoxaemia and hypercapnia are to be avoided.Some i.v. agents may also be given by s.c. or i.m.injection but these routes of administration are notrecommended for routine induction of anaesthesiabecause of variable absorption and difficulty ingauging the dose.INTRAVENOUS TECHNIQUEFIG.15.3 Restraint for injection into the cephalic vein.Intravenous injections in dogs are commonlymade into the cephalic vein, but other convenientsites include the lateral saphenous vein, thefemoral vein, the jugular vein and, in anaesthetizedanimals, the sublingual veins. Whicheversite is used, conscious dogs should be handled quietlyand forcible restraint reserved for those occasionswhen it is essential. Muzzles may benecessary in dogs showing an inclination to bite.The muzzles should be of the type with a quickrelease catch as delay in removal of a muzzle tangledin facial hair in a dog that has vomited duringinduction of anaesthesia may lead to inhalation ofthe vomited material.Haematoma formation after venepunctureshould be prevented by application of pressureto the site for an adequate period – usually abouta minute. A haematoma is not only painful forthe patient; it may prevent subsequent use ofthe particular vein for venepuncture for severaldays. Where a vein has been entered duringan unsuccessful attempt at venepuncture, thepressure which was keeping the vein distendedshould be released and firm pressure applied tothe site to stop bleeding before another attempt ismade.If the vein on the right forelimb is to be puncturedan assistant stands on the left side of the animal,passes his or her left arm around the animal’sneck and raises its head (Fig. 15.3). The assistant’sright hand grips the animals right forelimb so thatthe middle, third and fourth fingers are immediatelybehind the olecranon and the thumb isaround the front side of the limb. The limb isextended by pushing on the olecranon and the veinis raised by applying pressure with the thumb. Thehand should be rotated so as to pull the cephalicvein slightly lateral, which straightens it andmakes it more visible. Venepuncture must be carriedout with the usual aseptic precautions, so hairover the vein is clipped and the skin is disinfected.It is an advantage to use syringes of more than2ml capacity that have an eccentrically placed nozzle,for this allows the syringe to rest securely on theforearm with the needle more or less flush to thevein. In this way, the angle of entrance, i.e., the anglebetween the needle and the vein, is small and consequentlythere is less risk of the needle beingpushed right through the vein. Suitable needlesizes depend on the size of the dog and the quantityand viscosity of the fluid to be injected. For mostpurposes a needle 2.5 cm long and 22 or 23 gauge issatisfactory; a 25 gauge needle can be used forsmall dogs. The point of the needle should not becut too acutely, the ‘short bevel’ being preferred.Two methods of stabilizing the vein prior toneedle puncture are employed. In one, the skinover the vein is tautened without flattening thevein by the anaesthetist’s free hand grasping thelimb distal to the site of venepuncture and gentlypulling the skin down. In this position it is easy forthe anaesthetist to adjust the handhold to grip thesyringe between thumb and forefinger once thevein has been entered. Usually the skin is penetratedin one move and then the vein entered in asecond move. Once blood is observed in the needlehub, the needle should always be threaded deeperinto the vein before making any injections.

400 ANAESTHESIA OF THE SPECIESFIG.15.4 Stabilization of the cephalic vein against thethumb.In the second method, the thumb of the anaesthetist’sfree hand is placed just alongside the vein,and the skin is not tensed (Fig. 15.4). The vein isstabilized between the needle and the thumb asthe needle is advanced through the skin into thevein. With this method it may be harder to threadthe needle up the vein and there is a greater tendencyto make contact between the needle point andthe branch of the radial nerve running alongsidethe vein.The first attempt at needle puncture shouldbe done distally in the limb so that, if a haematomaforms, further attempts can be made moreproximally. In Dachshunds and dogs with similarshort, bent forelimbs venepuncture is bestattempted in the angle where the accessory cephalicand cephalic veins join just cranial to the carpus(Fig. 15.5).All air should be expressed from the syringebefore venepuncture is attempted and there mustbe sufficient space left in the syringe to allow slightwithdrawal of the plunger in order to test whetherthe needle is within the lumen of the vessel. Bloodshould enter the syringe when this is done, and noFIG.15.5 In short-legged dogs such as Dachshunds withvery mobile skins the easiest point for venepuncture is atthe junction of the veins from the medial and lateralaspects of the carpus where they unite to form thecephalic vein.injection must be made if blood does not appear inthe syringe or needle hub. Failure to draw bloodusually means that either the vein has not beenentered, the needle tip has passed through theopposite wall of the vein, or that the needle hasbecome occluded. Failure to aspirate blood intothe syringe is also encountered if the assistant hasreleased occlusion pressure on the vein, if the veinis already thrombosed, or when peripheral perfusionis poor as it may be after administration of anα 2 adrenoceptor sedative.The lateral saphenous vein may be used for i.v.injection at the point where it passes obliquely onthe lateral aspect of the hindlimb just proximal tothe tarsus. The dog is usually restrained on its sidebut two assistants may be required for an alertdog. One restrains the head and forelimbs whilethe other holds the underneath leg immobilizedwith one hand and holds the upper limb in fullextension by pressure on the stifle while raisingthe vein as shown in Fig. 15.6. Two hands may beneeded to immobilize the limb and raise the vein

THE DOG 401FIG.15.6 Lateral saphenous vein.in very large or active dogs. The lateral saphenousvein is usually more prominent than the cephalicvein but it is more mobile and therefore more difficultto puncture. When the needle has been introducedwell into the vein the needle is fixed to theleg by pressing on the needle hub with thumb, orthumb and forefinger, while the fingers encirclethe limb.The femoral vein in the middle part of the medialaspect of the thigh may also be used. It isrendered obvious by pressure applied to theinguinal region and is usually more prominentin the cranial part of the thigh. Care should betaken to ensure that injections are not made intothe femoral artery which lies directly beneath thevein.Venepuncture of the jugular vein in the dog canbe done with the dog standing or sitting with thehead raised (Fig. 15.7). Particularly in smaller or illpatients, it is easier when the animal is restrainedon its side and the vein is raised by occlusion nearFIG.15.7 Jugular venepuncture in the conscious sittingdog.the sternal inlet. A small foam pad, towel, or sandbagplaced under the neck of the dog makes theposition of the vein more obvious.Short catheters (18 gauge and 20 gauge, 5 cmlong, or 20 gauge or 22 gauge, 2.5 cm long) arecommonly inserted into the cephalic or lateralsaphenous veins prior to induction of anaesthesiafor administration of anaesthetic drugs, electrolytesolutions and supportive drugs. All of the veinsdescribed, cephalic, saphenous, femoral, andjugular, can be used for placement of longercatheters (18 gauge and 22 gauge, 20–30 cm long)when the animal is likely to need several daysof treatment with i.v. solutions and drugs afteranaesthesia.Securing a catheter in the jugular vein is moredifficult than in a limb. The external end of thecatheter is positioned so that it is pointing towardthe back of the neck; several folded gauze spongesare placed under the free end of the catheter whichis then stabilized by wrapping 2 or 3–inch gauzearound the neck and this then secured by white

402 ANAESTHESIA OF THE SPECIEStape and vetwrap or elastic bandage. When acatheter-through-the-needle product is used, theneedle usually cannot the removed after thecatheter has been inserted in the vein. The needleguard provided should be clipped over the needleand the needle and catheter hubs glued togetherwith a drop of ‘superglue’.The sublingual veins may be used for i.v. injectionsin anaesthetized dogs. The tongue is pulledover the anaesthetist’s finger so that its ventral surfaceis exposed and injection is made into one ofthe easily visible veins. It is important to use asmall (25 gauge) needle because the vein will bleedvery freely after the needle is withdrawn. Pressureshould be applied to the site for several minutes toavoid large sublingual haematoma. However, incase of emergency and absence of any otherperipheral venous access, an 18 gauge catheter canbe inserted in the lingual vein of medium sizeddogs for administration of a large volume of electrolytesolution or blood. These veins are also usefulfor collecting blood to measure the packed cellvolume and total protein during anaesthesia andsurgery.Intraosseous injectionPlacement of a catheter in a vein is occasionallydifficult in dehydrated animals, especially toybreeds and puppies. The intraosseous route is anacceptable alternative for administration of fluids,blood, and drugs. Absorption of drugs is rapid andwithin one minute for some drugs, such asatropine. Intraosseous injection implies injectioninto the intramedullary canal of the femur, tibia, orhumerus using either a Cooke intraosseous needle,a Jamshidi needle or a spinal needle. A20 gauge, 2.5 cm spinal needle is satisfactory forthe smallest dogs and is inserted asepticallythrough the trochanteric fossa of the femur andparallel to the long axis of the bone into themedullary cavity. The stilette is removed, the needleflushed with heparinized saline, a T-port isattached and flushed again. Bandaging must besecure to prevent the needle from being dislodgedas the animal moves about. Potential complicationsinclude infection and exceptional care shouldbe taken in maintaining sterility of injections. Theneedle should be removed after 72 hours.Vascular portThe vascular port is a subcutaneously implantedsystem for i.v. delivery of drugs. It is used whendogs require multiple anaesthesias over a shorttime, for example for radiotherapy, and theperipheral veins are badly thrombosed. The vascularport consists of two basic parts: an indwellingcatheter that is threaded into the jugular vein aftersurgical dissection in the anaesthetized dog and arigid puncturable bulb that looks like a volcanoand is located subcutaneously in the neck. Thebulb has a silicone rubber window that is easilypalpated through the skin and allows percutaneousintravenous injections using an appropriateneedle.INTRAVENOUS AGENTSIntravenous agents may be administered alone butare usually given after preanaesthetic sedation.Induction of anaesthesia will then be calmer, feweradverse side effects of the induction drugs will beobserved, their margin of safety will be increased,and recovery may be faster. Some commonly useddrug combinations, with dose rates, are given inTable 15.4.ThiopentalSolutions of thiopental have a high pH and thedrug can only be given i.v. It should always beused in dogs as a 2.5% or weaker solution for moreconcentrated solutions are unnecessary and dangerous.A 5% solution increases the total quantityof the drug required, causes thrombosis of the veinand, if any is injected perivascularly, produces aserious slough of the overlying tissues and skin.Injection of any quantity of even a 2.5% solutioninto the tissues outside the vein is an indication forthe immediate injection into the area of 2 mg/kg oflignocaine (lidocaine) without adrenaline to precipitatethe thiopental into a harmless salt, and upto 20 ml of saline for dilution of the irritant.The dose of thiopental depends on the conditionof the dog, its state of hydration and, particularly,on previous medication. For these reasonsthe dose rate is often stated to be ‘sufficient and nomore’ but as a rough guide the anaesthetist should

THE DOG 403expect to have to use up to 12 mg/kg in a dogfor induction of anaesthesia. In the healthy butlightly premedicated dog, one half of this, i.e.about 6 mg/kg is given rapidly as a bolus of a 2.5%solution should produce a rapid induction ofanaesthesia and a smooth transition to inhalationanaesthesia. If anaesthesia is insufficient to permitendotracheal intubation, additional small incrementsof the remainder should be given at 20–30second intervals. The whole dose may be neededin a proportion of dogs and when the drug is givenmore slowly. Large dogs require relatively lessthan small, while geriatric dogs have a reducedanaesthetic requirement. A lower dose of 5–6 mg/kg of thiopental may be sufficient in dogs providedwith a moderate degree of preanaesthetic sedationfrom a combination of sedative and opioid,such as acepromazine and butorphanol. The doseof thiopental required for induction will be greatlydecreased to 1–3 mg/kg in dogs that are heavilysedated, for example with acepromazine andmorphine, xylazine and butorphanol, or medetomidine.Other drugs may be administered i.v. immediatelybefore thiopental to decrease the dose neededand to enhance the quality of induction. Diazepamor midazolam, 0.1–0.2 mg/kg, may decrease thedose of thiopental required by 15% or more,depending on the physical status of the dog.Potent opioids such as alfentanil may greatlyreduce the thiopental dose required to induceanaesthesia. Alfentanil, 5 µg/kg, given over 30 secondsbefore thiopental may reduce the thiopentaldose to about 3 mg/kg. A dilute solution of alfentanilshould be used to facilitate slow injectionwhich will minimize the occurrence of apnoeaafter thiopental injection. Atropine or glycopyrrolateshould be given prior to or concurrently withalfentanil administration to prevent bradycardia.The consequences of reduced thiopental doserate by prior administration of premedicant orother anaesthetic agents are two-fold. First, overdosageand cardiac arrest are a possibility andalways the anaesthetist should assess the dog’sneed for thiopental based on the degree of centralnervous depression and cardiovascular stability.Secondly, low dose administration of thiopentalmeans that the drug will be rapidly redistributedso that the duration and quality of recovery arerelated to the other agents used. When the otheragents are rapidly eliminated or their action can bepharmacologically antagonized, recovery fromanaesthesia is more rapid than when a higher doseof thiopental alone has been administered.In dogs, thiopental is very slowly metabolizedand attempts to prolong anaesthesia with multipleor higher doses which saturate the body fat resultin very prolonged anaesthesia followed by ‘hangover’for 24 or more hours. In thin dogs such asBorzois, Afghans, and Greyhounds (Greyhoundsmay also be deficient in the liver enzymes necessaryfor detoxification of thiopental), this level isreached very rapidly, and little more than the minimuminduction dose may be given with safety. Infact, recovery will be more satisfactory in theseanimals if thiopental is omitted and inductionachieved by administration of a more rapidlymetabolized agent such as propofol.Thiopental differs from some other intravenousagents in that high doses cause severe respiratorydepression so that prolonged anaesthesia cannotbe produced by an initial high dose, but must bemaintained by incremental doses. Where thiopentalis used as the sole anaesthetic, recovery may beviolent and noisy. Sedative premedication can preventthis, so should always be employed, but if it isomitted, a sedative or analgesic should be given atthe end of anaesthesia.The maximum total dose of thiopental for ahealthy dog is about 25 mg/kg – and this wouldrepresent a gross overdose in a sick animal.Recovery is prolonged after a dose of this magnitude.Because of its lack of analgesic properties,attempts to use thiopental for painful procedures,even short ones, tend to result in overdosage. It isfar preferable to provide a base of sedation andanalgesia with other drugs so that only smalldoses of thiopental must be injected to producethe minimum of respiratory depression whileonly just abolishing or modifying the response tostimulation.In the absence of surgical stimulation the firstindication that thiopental anaesthesia is passingoff is that stiffening of the jaws and curling of thetongue occur when the mouth is opened. Theremay be licking of the nose and from this pointrecovery is rapid. The time taken to assuming sternalposition will then depend on the lingering

404 ANAESTHESIA OF THE SPECIESeffects of premedication or provision for postoperativeanalgesia. After light preanaesthetic sedation,when no other anaesthetic agent has been given toprolong anaesthesia, the dog is obviously quiteconscious and aware of its environment about halfan hour after induction . Limb coordination, especiallythe hind, is delayed, and the dog may staggerin a drunken manner for about an hour.MethohexitalAlthough recovery from a single bolus dose ofmethohexital is due mainly to redistribution to themuscles and body fat, the drug is rapidly eliminatedfrom the body by metabolism and excretionso that dogs recover from even large doses quickly.In general it is advisable to use sedative premedicationto smooth induction and recovery, becausewithout such sedation both periods may be violent.Doses of 4 to 6mg/kg i.v. in a 1 or 2% solutionare suitable for the induction of anaesthesia indogs premedicated with acepromazine, and furthersmall increments given as required may beused to prolong anaesthesia. The method of injectionis similar to that for thiopental, although aslightly slower rate of initial injection is less likelyto result in apnoea. Because of its rapid eliminationfrom the body, recovery after prolongedmethohexital anaesthesia usually occurs withinhalf an hour of the last dose being given. Overdoseproduces severe respiratory depression, and evenanaesthetic doses produce more respiratorydepression than equipotent doses of thiopental.Depression of cardiac output with low anaestheticdoses is also greater than after equipotent doses ofthiopental (Clarke & Hall, 1975). Cumulation and,therefore, delayed recovery occurs in doses inexcess of 10–12 mg/kg.Because recovery is so rapid and complete,methohexital is most useful for outpatient anaesthesiaand induction of anaesthesia in brachycephalicdogs, thin dogs, young dogs, and for caesariansection. Even in these animals, however, methohexitalhas largely been replaced by propofol.PentobarbitalPentobarbital was formerly widely used in canineanaesthesia and there can be no doubt that at thetime of its introduction in the early 1930s it causeda revolution in small animal practice. By the end of1938 the slow intravenous injection of pentobarbitalhad been used to produce anaesthesia in morethan 2000 operation cases at the Beaumont Hospitalof the Royal Veterinary College, London, byJ. G. Wright and his colleagues. Pentobarbital soonbecame the standard agent for producing anaesthesiaof about an hour’s duration. Althoughpentobarbital is not often used now, it is occasionallyused in the intensive care unit to producedeep sedation in dogs with neurological diseaseand it is still widely employed in experimentallaboratories.After weighing the dog the approximate dose isestimated on a basis of about 30 mg/kg bodyweight. In healthy unpremedicated animals, abouta half to two-thirds of the computed probable doseis injected rapidly intravenously in order to ensurethat the dog passes quickly through the excitementphase of induction of anaesthesia. Because theonset of action of pentobarbital is much slowerthan that of thiopental, the remainder of the dose isadministered in increments over 3–5 minutes,pausing after the injection of each increment andassessing its effect. When complete relaxation ofthe head and neck is obtained, relaxation of thejaws is assessed. Opening the mouth provokesmovement of the tongue and jaws varying from acomplete yawn to a slight curling of the tip of thetongue. A little more of the anaesthetic is injectedand after an appropriate wait the jaws are againopened. The aim is to reach the point at which thejaws are completely relaxed and the tongue, whendrawn out, hangs limply.When this is attained, a light level of unconsciousnesscan be assumed. The corneal reflex ispresent, the pupil reacts to light and the pedalreflex is brisk. Respirations are regular and deep.This is the degree of anaesthesia to be induced forsuperficial operations. If it is decided to inducedeeper unconsciousness with pentobarbital, theso-called ‘pedal reflex’ is then used as the index ofdepth. If the web between the digits, or the nailbed, is pinched firmly with the finger and thumbnails, it will be found that the pedal reflex comprisesa definite upward and backward jerking of thelimb. Often the response continues for several secondsafter the stimulus has ceased. Administration

THE DOG 405is slowly continued until the reflex is just lost andthen the depth of unconsciousness is adequate forthe performance of intra-abdominal procedures.When used to control seizures in a patient withneurological disease, pentobarbital must be givenover several minutes in small increments to avoidoverdosage, as the dose in these patients may be aslow as 4 mg/kg.PropofolPropofol, as the free-flowing oil-in-water emulsionwhich does not give rise to histamine release, iscommonly used in dogs (Hall, 1984; Watkins et al.,1987). The dose for induction of anaesthesia inunpremedicated dogs is 6 mg/kg and premedicationwith 0.02–0.05 mg/kg of acepromazinereduces this to about 4 mg/kg. Females are moresusceptible than males, the induction dosein unpremedicated females being 5.23 mg/kg(SD 1.58, n = 68) and in males 5.74 mg/kg (SD 1.53,n = 39) (Watkins et al., 1987). Administration ofpropofol for induction of anaesthesia is similar tothiopental in that one-half of the anticipated doseis administered initially as a bolus but the initialadministration should be slower to avoid or minimizeapnoea. Recommendations for the rate of theinitial bolus vary from rapid to up to 3 minutes.However, administration of half the anticipateddose over 30 seconds seems to be satisfactory.Administration of O 2 by facemask during inductionto prevent cyanosis is advisable, particularlyin geriatric and sick dogs. The cyanosis occurringat induction of anaesthesia with propofol in somedogs has been attributed to apnoea, a transientdecrease in arterial blood pressure, or opening ofpulmonary shunts.After induction, propofol may be given in incrementaldoses as needed to maintain anaesthesia.In dogs premedicated with an anticholinergicand acepromazine (0.03 mg/kg) or butorphanol(0.2–0.3 mg/kg) anaesthesia can be maintainedby continuous infusion of propofol at a rate of0.3–0.4 mg/kg/min (Fig. 15.8). Anaesthesia maybe light for surgical procedures and muscle rigiditymay be present in some animals. Retching andvomiting have been encountered in the recoveryperiod in 16% of dogs after continuous infusion ofthe agent. Dogs left unstimulated in the recoveryFIG.15.8 Syringe driver (Medex Inc.,Duluth,Georgia,USA) for continuous administration of propofol or otheranaesthetic agents or fluids.period appear to sleep – arousal during this stagecan result in immediate awakening with an abilityto walk without ataxia. Dogs given one dose ofpropofol recover completely in about 18 minutesfrom the time of injection and those given intermittentinjections recover in about 22 minutes fromthe time of injection of the final increment.Preanaesthetic sedation will prolong recoveryaccording to the drugs used.Propofol has been used for induction of anaesthesiain dogs after a variety of medications.Medetomidine, 20–40 µg/kg, decreases the inductionof dose of propofol to 2–4 mg/kg (2 mg/kgafter the high dose of medetomidine) and the doserate for maintenance of anaesthesia to 0.15–0.2 mg/kg/min (Vanio, 1991; Hall et al., 1997;Hellebrekers et al., 1998). Alfentanil, 10 µg/kg i.v.mixed with 0.3 mg atropine, given one minutebefore induction of anaesthesia also decreased thedose of propofol for intubation to 2 mg/kg(Chambers, 1989) but apnoea of more than 3 minutesduration occurred in 11% of dogs and 6%showed twitching or paddling, usually of the forelimbs.Later trials (Hall, unpublished observations)demonstrated that a dose of 5 µg/kg of alfentanil,mixed with atropine, given over 30 seconds resultedin less apnoea without significantly increasingthe subsequent dose of propofol needed. Recoveryfrom injection to full awakening (no ataxia) is ofthe order of 7 minutes – a very fast recovery.The effect on respiratory rate is variable butdogs which are panting before the induction of anaesthesiaare likely to continue to do so throughout

406 ANAESTHESIA OF THE SPECIESanaesthesia. Induction of anaesthesia in healthydogs with propofol produces dose-dependent respiratorydepression. Respiratory rate and minuteventilation decrease with a transient mild increasein PaCO 2 (Quandt et al., 1998). No significantchanges in HR, MAP or CO were measured.Others have concluded that although propofolmay preserve MAP and CO if the preload is maintained,propofol may decrease MAP and CO secondaryto a reduction in preload by a directvenodilator effect. Administration of propofol indogs made hypovolaemic by withdrawal of 37% oftheir estimated blood volume resulted in a seriousdecrease in MAP (Ilkiw et al., 1992). Premedicationwith different agents alter the cardiovascularresponse to propofol. Medetomidine, for example,results in increased MAP such that arterial pressureis maintained after administration of propofol.Like thiopental and halothane, myocardialsensitivity to the effects of catecholamines isincreased by propofol and propofol should beused cautiously in patients at risk for ventriculararrhythmias, such as occur in cardiomyopathy andmyocardial ischaemia or contusions.Propofol may be a good choice for induction ofanaesthesia in dogs with seizures, meningitis, braintumours, or spinal cord disease as it decreasesintracranial pressure. Likewise, propofol decreasesintraocular pressure and may be used satisfactorilyfor induction of anaesthesia in dogswith severe corneal ulcers or those scheduled forintraocular procedures.KetamineThe dose of ketamine which produces anaesthesiain dogs produces excessive muscle tone and spontaneousmuscle activity and is near to that whichcauses convulsions. Thus, ketamine cannot berecommended as a sole agent for canine anaesthesia.It can be used in combination with varioussedative agents to induce anaesthesia for shortterm procedures or for maintenance with halothane,isoflurane, or sevoflurane. Unless specificallycontraindicated anticholinergics may beadministered for premedication to reduce the salivationinduced by ketamine, or to prevent thedecrease in heart rate induced by xylazine ormedetomidine.A common combination used for inductionof anaesthesia is 0.25 mg/kg of diazepam and5 mg/kg of ketamine given intravenously at thesame time (equivalent to combining 5 mg/ml ofdiazepam and 100 mg/ml of ketamine in the samesyringe as a 50:50 mixture and dosing at a rate of1 ml of the mixture per 10 kg of body weight).Premedication may also include acepromazine, oran opioid, or a tranquillizer-opioid combination.Frequently one half to two-thirds of the calculateddose is administered rapidly initially and theremainder administered in increments as needed.The onset of action is much slower than thiopentaland the signs of anaesthesia differ. Up to oneminute may elapse after injection of ketaminebefore endotracheal intubation can be accomplishedand even then there is little relaxation ofthe jaws; the eyelids will be wide open and a briskpalpebral reflex should be present.Ketamine, 10 mg/kg i.v., to dogs results inincreased HR, MAP, CO and systemic vascularresistance that is attributed to a centrally mediated,generalized increase in sympathetic tone (Haskinset al., 1985). The combination of diazepam and ketamineproduces similar effects (Haskins et al.,1986). Although the preservation of cardiovascularfunction is useful in ill dogs, the significant increasein heart rate may induce rhythm problemsin dogs with an ischaemic or damaged myocardium.Administration of ketamine to experimentaldogs with haemorrhagic hypovolaemia revealedthat ketamine supported cardiovascular functionwell (Haskins & Patz, 1990). However, inductionof anaesthesia in critically ill dogs with ketaminein combination with diazepam or an opioid mayusually be accomplished safely but using reduceddose rates.In the past, the combination of xylazine,1mg/kg, and ketamine, 10 mg/kg, given either i.v.or i.m. has been used for short term anaesthesia.However, severe cardiopulmonary changes havebeen measured during anaesthesia with this drugcombination such that there is concern about thesafety of its use in old and sick dogs. CO is significantlydecreased, and HR and ABP are increased,for 30 minutes following i.v. xylazine and ketamine(Kolata & Rawlings, 1982). The combinationalso produces moderate hypercapnia, acidaemia,and hypoxaemia for 20 minutes. Respiratory arrest

THE DOG 407is occasionally noted in clinical dogs anaesthetizedwith xylazine-ketamine. The more recent introductionof medetomidine has revived interest inthe use of an α 2 agonist sedative-ketamine combinationfor injectable anaesthesia. The clinicalfeatures of anaesthesia in healthy dogs with medetomidine,1000µg/m 2 body surface area(approximately 40 µg/kg in a 25 kg dog), administeredintramuscularly 10–15 minutes before i.v.ketamine, 3–4 mg/kg, have recently been reported(Hellebrekers & Sap, 1997; Hellebrekers et al.,1998). The duration of anaesthesia from singledosing was 54 ± 31 minutes (mean ± SD).Administration of ketamine reversed the medetomidine-inducedbradycardia and caused hypertensionwith MAPs at 150 mmHg (Hellebrekers &Sap, 1997). Recovery from anaesthesia with ketamineis often associated with restlessness orhyperactivity and indeed, only 63% of recoveriesfrom medetomidine-ketamine were judged tobe smooth; this is in contrast to 89% of anaestheticsutilizing medetomidine-propofol (Hellebrekerset al., 1998).Tiletamine-zolazepamIn those countries where tiletamine is available itis obtained in a premixed combination with thebenzodiazepine, zolazepam, under the tradenames of Telazol and Zoletil. The drug preparationconsists of 500 mg of lyophilized tiletaminezolazepam(250 mg of tiletamine and 250 mgof zolazepam) which is reconstituted with sterilewater. The doses reported are the sum oftiletamine and zolazepam doses so that 4 mg/kgof Telazol is equivalent to 2 mg/kg of tiletamineand 2 mg/kg of zolazepam. Initial studies ofthis drug combination were with higher doserates than are now used commonly. Tiletaminezolazepam,4 mg/kg, i.m. with an anticholinergicprovides effective sedation for aggressive or dangerousdogs. Sedation is profound but ranges fromthe dog being just capable of walking to the dogthat is almost unconscious and ready for trachealintubation. Onset of adequate sedation may bewithin minutes or up to 10 minutes. An alternativetechnique is to use lower doses of tiletaminezolazepami.v. to achieve anaesthesia for trachealintubation prior to inhalation anaesthesia.HR, MAP, and CO are increased by tiletaminezolazepambut larger i.v. doses result in a transientand severe decrease in MAP (Hellyer et al., 1989).EtomidateEtomidate is a short acting non-barbiturate i.v.anaesthetic. Its main feature is that induction ofanaesthesia with etomidate is accompanied by littleor no change in cardiovascular function andwith less myocardial depression than thiopental,and etomidate does not predispose the heart toarrhythmias. Even in experimental dogs madehypotensive and hypovolaemic by haemorrhage,little cardiovascular change was measured duringanaesthesia with etomidate (Pascoe et al., 1992).Etomidate decreases intracranial pressure. Thus,the main indication for use is for dogs with cardiovascularcompromise, such as cardiomyopathy,pericardial tamponade, sick sinus syndrome, or fordogs that are in haemorrhagic shock. Etomidate i.v.can be associated with undesirable side effects suchas excitement, myoclonus, pain on injection, vomiting,and apnoea (Muir III & Mason, 1989). Theseeffects should not be observed if etomidate,0.75–1.5 mg/kg, is given after premedication withan opioid or diazepam. The technique of administrationof etomidate is similar to that of thiopental,with half of the calculated dose (the dose used ismodified by the evaluation of the individual dog’sclinical condition) being given as a bolus injectionand additional drug given in increments.An important additional side effect of etomidateis that it interferes directly with adrenocorticalproduction of corticosteroids andaldosterone. Reduced cortisol response to thestress of surgery in comparison to thiopental wasmeasured for up to 6 hours after induction withetomidate, 2 mg/kg (Dodam et al., 1990). For thisreason, anaesthesia should not be maintained byadditional injections of etomidate beyond the calculateddose. Exogenous steroid can be administeredif necessary.NeuroleptanalgesiaSome combinations of neuroleptanalgesia are sufficientlypotent to induce anaesthesia that is adequatefor endotracheal intubation in old or sick

408 ANAESTHESIA OF THE SPECIESdogs. The dogs initially may be responsive to noiseand endotracheal intubation must be performedquietly and gently followed by administration ofsufficient inhalation agent to deepen anaesthesia.The administration of this type of induction isslightly more prolonged (over 2–3 minutes) thanbolus injections of thiopental or propofol, however,the main advantage is preservation of haemodynamicstability (Haskins et al., 1988). The drugsused for induction of anaesthesia may also be continuedduring surgery either as sole agents or toprovide a substantial base of sedation and analgesiasuch that a very low concentration of inhalationagent is required. Large doses of opioids frequentlyinduce bradycardia and administration of an anticholinergicmay be advisable. In old and sick dogsgiven opioids IPPV may be necessary to correcthypoventilation. Preoxygenation is recommended.Diazepam or midazolam, 0.2 mg/kg, with oxymorphone,0.1–0.2 mg/kg, can be injected i.v. inalternate increments, flushing the catheterbetween injections, until all the benzodiazepineand as much of the oxymorphone as necessary forinduction has been administered. A similar techniqueinvolves administration of diazepam,0.2mg/kg, and fentanyl, 2–5 µg/kg. Another combinationrecommended for cardiovascularly compromizeddogs, including those with gastricdilatation/volvulus is sufentanil-midazolam(Hellebrekers & Sap, 1992). Mean doses forinduction are 3 µg/kg sufentanil and 0.9 mg/kgmidazolam. This combination has been continuedfor maintenance of anaesthesia without additionalinhalation agent and the mean dose per hour wasthe same as the induction dose, namely 3 µg/kg/hsufentanil and 0.9 mg/kg/h midazolam (Hellebrekers& Sap, 1992); IPPVwas applied throughoutanaesthesia. A combination of metdetomidine,1500µg/m 2 body surface area, with fentanyl,2 µg/kg, resulted in satisfactory induction ofanaesthesia in healthy dogs but attempts to maintainanaesthesia with fentanyl were unsatisfactory,producing severe respiratory depression and theneed for O 2 (Hellebrekers & Sap, 1997).Alphaxalone-alphadaloneSaffan is marketed for use in cats but it is specificallycontraindicated by the manufacturers for usein dogs, as it is solubilized in Cremophor EL – acompound which may cause massive release ofhistamine in all Canidae. Although it has beenclaimed that following heavy premedication withpotent antihistamines Saffan can be used safely indogs, reports to the Association of VeterinaryAnaesthetists of Great Britain and Ireland indicatethat even after this premedication Saffan administrationcan be followed by anaphylaxis. It is theauthors’ view that, given that safer alternativesexist, Saffan should not be administered to dogs.INHALATION ANAESTHESIAA wide variety of inhalation agents has been usedin the past for canine anaesthesia. The choice ofagent or agents in any particular case is largelygoverned by the limitations of each agent and relativecontraindications imposed by the abnormalitiesof the dog. The properties of the gaseous andvolatile agents currently employed in dogs whichimpact on the agent selection are summarized inTable 15.5.The inhalation agents may be used in dogs bothto induce or maintain anaesthesia or, morecommonly, to maintain anaesthesia which hasbeen induced with an i.v. agent. Induction ofanaesthesia with i.v. agents is rapid and pleasantfor the animal. Induction of anaesthesia withthe inhalant agent using a facemask is usuallyonly done in lightly sedated puppies or old dogs,TABLE 15.5 Properties of inhalation agentscurrently used in dogsAgent Rapidity Analgesic Otherof action activity propertiesHalothane ++ Poor Hypotension,respiratorydepressionIsoflurane +++ Poor Hypotension,respiratorydepressionNitrous oxide ++++ Good Inadequateon its ownSevoflurane ++++ Poor Hypotension,respiratorydepression

THE DOG 409and in other dogs that are moderately or heavilysedated.INDUCTION USING A FACEMASKFacemask induction is slower than induction withinjectable agents and pollution of the room withanaesthetic gases usually occurs. The dog shouldbe placed on a table at a convenient height andgently restrained by an assistant. The facemask islightly placed over the dog’s nostrils with only O 2flowing to accustom the animal to the feel of theprocedure. When the dog is quiet, the inhalationagent can be introduced and vaporizer settingshould be increased by 0.5% increments afterevery three or four breaths. The face mask shouldbe applied closely to the dog’s face only when consciousnessis lost. Attempts to introduce a highconcentration of anaesthetic immediately througha closely fitted mask to a conscious dog will resultin struggling, breath holding and excitement.When a non-rebreathing system is used for anaestheticdelivery, the inspired anaesthetic concentrationwill change within seconds of a change in thevaporizer setting. The increase in inspired concentrationwill be more gradual and, therefore, inductionslower when a rebreathing system such as acircle is used. The O 2 flowmeter setting will begoverned by the type of system in use, with moderateto high O 2 flows used during mask inductionwith a rebreathing circuit and an out-of-circlevaporizer. The maximum vaporizer setting usedduring induction should depend on the degree ofpreanaesthetic sedation, the type of delivery system,and the health of the dog. When a halothanevaporizer is set to above 2.5%, or the isofluranevaporizer to above 4%, the anaesthetist mustclosely observe the progression of anaesthesia toavoid overdosage. Inclusion of 50–66% nitrousoxide from the start of administration will increasethe speed of induction of anaesthesia by utilizingthe ‘second gas’ effect (Chapter 6). Inductionwill also be rapid with sevoflurane. When a rebreathingsystem is to be used for maintenanceof anaesthesia in a small dog, induction may befacilitated by use of a non-rebreathing system duringinduction and connecting the dog to therebreathing system after tracheal intubation.When a rebreathing system is used for induction, itmay be advisable to express the low anaestheticconcentrations from the rebreathing bag periodicallyduring the induction phase and then toexpress the highest anaesthetic concentration fromthe rebreathing bag before connecting the dog tothe anaesthetic system after endotracheal intubation.In all cases the anaesthetist must remember todecrease the vaporizer setting to a safe level beforeconnecting the endotracheal tube to the breathingsystem.In circuits such as the Stephens machine, wherethe vaporizer is incorporated within the breathingcircuit, each breath of the dog serves to vaporizemore anaesthetic and the effect is maximal whenthe O 2 inflow rate is low. The rebreathing bagshould also be emptied several times duringinduction to minimize accumulation of exhaled N 2within the circuit.SYSTEMS OF ADMINISTRATIONThe different types of breathing systems which areavailable are described in Chapter 9 and the choiceof system will depend on the size of the dog.Resistance to breathing in the circuit and apparatusdeadspace should be low for small dogs.Suitable circuits include the T-piece, Normanelbow, Magill circuit, and the coaxial circuits suchas the Bain or Lack systems. An advantage to useof these systems is that the inspired anaestheticconcentration is the same as that leaving thevaporizer, so that it is easier to maintain a stablelevel of anesthesia or to quickly change the depthof anaesthesia. The inspired concentration ofanaesthetic agent changes within seconds ofchanging the vaporizer setting. Disadvantagescompared with rebreathing systems are the greaterdecrease in body temperature that may occurbecause the inspired gases are dry, and theincreased cost of anaesthesia because high gasflows are required and more anaesthetic agent isvaporized and wasted. Inclusion of a disposablehumidifier between the endotracheal tube and thecircuit will help to retain exhaled water vapor and,by moistening inspired gas, slow the rate of fall inbody temperature.Rebreathing systems used to administer inhalationanaesthesia include the circle and to-and-frosystems which contain carbon dioxide absorbers.

410 ANAESTHESIA OF THE SPECIESTheir main advantage over non-rebreathing systemsis that they are economical in use because lowO 2 flows are used and less anaesthetic agent isvaporized. Furthermore, heat is generated by theaction of the exhaled CO 2 on the soda lime in theabsorber, water vapour is conserved in the circuitand the dog consequently breathes warm, moistgases. Dogs with a heavy hair coat, anaesthetizedin a warm room using a rebreathing circuit candevelop hyperthermia.The resistance to breathing offered by the CO 2absorbent may contribute to hypoventilation insmall dogs. The smallest size of animal that shouldbe connected to a circle circuit usually used forhuman adults (internal diameter 22 mm) is controversial.Paediatric hoses (internal diameter 15 mm)where available may be substituted for animalsbetween 3 and 8 kg bodyweight. Resistance tobreathing in these small sized dogs may result infailure to move gases through the absorber andresult in rebreathing of CO 2 . This inability to overcomethe resistance of the soda lime may be counteredby maintaining an oxygen flow of 1 l/minwhich will facilitate movement of gases aroundthe circle and using IPPV.The to-and-fro rebreathing system with a sodalime canister capacity of 0.5 kg is usually used indogs weighing more than 10 kg and has the disadvantageof increasing dead space with use. Thepresence of the soda lime canister close to thedog’s head is physically awkward.Low-flow administration of inhalationanaestheticsA low-flow system can be defined as one in whichthere is substantial rebreathing of previouslyexpired gas which has passed through a CO 2absorber (usually in a circle system). The minimumO 2 flow that can be delivered safely to acircle circuit is a flow equal to the animal’smetabolic oxygen consumption (approximately6 ml/kg/min). This is called a closed system ofadministration because there is no excess oxygento be discharged through the ‘pop-off’ valve. Aclosed system does not require that the ‘pop-off’valve be shut closed because the valve is designedto remain closed until a pressure builds within thecircuit. During low-flow administration, the O 2inflow exceeds metabolic needs and a smallamount of waste gases will enter the scavengingsystem after each exhalation. An O 2 flow of lessthan 15 ml/kg/min is usually considered to below-flow anaesthesia.When low-flow administration is employedwith an out-of-the-circuit vaporizer, the number ofmolecules of inhalation agent delivered to the circleper unit time is low in proportion to the uptakeof agent into the patient’s body. Consequently,exhaled gas low in agent exerts a significant dilutingeffect on the percent concentration of freshagent entering the circle. The circle anaestheticconcentration may be lower than (down to onehalf)the vaporizer setting. Thus, the vaporizer settingmay have to be higher than 1.5–2.0 MAC inorder to achieve a sufficiently high inspired anaestheticconcentration to maintain anaesthesia.Changes in circuit anaesthetic concentration willdevelop only slowly after the vaporizer setting ischanged. When the concentration must beincreased quickly, such as when the dog is toolightly anaesthetized for surgery, the vaporizersetting must be increased for a few minutes andthen decreased to a value just above the original.Alternatively, the circle anaesthetic concentrationcan be increased rapidly by increasing the O 2 flowto 1 l/min. It must be realised that excessive anaestheticadministration can occur if the O 2 flow isincreased from an established low-flow system.The circle concentration will have been low and ifthe vaporizer setting is at a percentage greater than2 MAC, increasing the oxygen flow will bring thecircle concentration up to deliver an excessive concentration.To ensure that there is enough anaesthetic agentin the circle in the early part of anaesthesia, it iscommon to use a high oxygen flow (1 l/min) in thefirst 15 minutes of anaesthesia to wash-out expirednitrogen and wash-in sufficient anaesthetic agent.The oxygen flow rate is then decreased when thetransition from injectable anaesthesia to inhalationanaesthesia has occurred. The vaporizer settingwill be determined not only by whether high orlow-flow administration is employed but also bywhich anaesthetic agents have been used forpremedication and induction of anaesthesia. Forhealthy dogs, the vaporizer must be high after

THE DOG 411diazepam-ketamine induction but low after tiletamine-zolazepaminduction or high dose medetomidinepremedication.Low-flow administration must never be usedwith N 2 O unless the inspired concentration of O 2is measured with an O 2 monitor. The concern isthat N 2 O will accumulate in a low-flow system,reducing the O 2 concentration to a value resultingBACDFIG.15.9 Endotracheal intubation as seen by a right handed anaesthetist.AThe assistant is holding the upper lips and theanaesthetist is drawing the tongue out of the mouth,protecting its undersurface by placing a finger over the dog’s incisorteeth.BThe epiglottis is almost completely obscured by the soft palate.CThe soft palate has been lifted by the tip of thetube to allow the tip of the epiglottis to come forward.DThe tip has been passed over the epiglottis,through the vocalcords and on towards the sternum.

412 ANAESTHESIA OF THE SPECIESin hypoxia. For practical purposes, the ratio ofO 2 to N 2 O will not be distorted if the O 2 and N 2 Oflow rates are each set at 30 ml/kg/min; at least750 ml/min of each (total flow 1.5 l/min) for a25kg dog. Higher flows should be used if the ratioof N 2 O to O 2 is increased to 2:1.Circle circuits which incorporate the vaporizerwithin the breathing circuit are designed for thelow-flow system of administration. It is the dog’sown ventilation that draws oxygen through thevaporizer and vaporizes the inhalation agent. Thelower the oxygen flow rate the more quickly thecircle anaesthetic concentration increases. If thevaporizer was not initially intended for use withthe highly volatile anaesthetic agents, only the lowand middle settings on the vaporizer are neededfor adequate anaesthetic delivery.Endotracheal intubationCuffed endotracheal tubes for dogs vary from2.5mm to 16.0 mm internal diameter (ID). The diameterof the largest tube which can be introducedinto the trachea is related to both the size and thebreed of the dog with the requirement that the tubeselected should be a good approximation of thetracheal lumen diameter but not a ‘push’ fit. Forexample, a 14 mm tube can usually be inserted inthe trachea of an adult German Shepherd and an11 or 12 mm tube used for most 25 kg dogs. In contrast,the Bulldog often has an exceptionally smalldiameterlaryngeal lumen and trachea for its bodyweight and a selection of smaller tubes should beavailable at anaesthetic induction of this breed.The tubes should be checked for length alongsidethe dog because the tip of the tube should notextend beyond the thoracic inlet into the chest.Excess tube extending outside the incisors contributesto deadspace and CO 2 breathing and,therefore, some tubes may have to be shortened bycutting off 2 to 6 cm length with scissors. Thinwalledendotracheal tubes (e.g. ID to OD differenceof mm) with small volume cuffs should bepurchased for use in puppies and very small dogsto allow the largest lumen size possible in theirsmall tracheas. Alternatively, uncuffed or Cole patterntubes can be used to eliminate the space occupiedby the cuff. IPPV and aspiration of foreignmaterial are potential problems with use ofuncuffed tubes and should be prevented by packingthe pharynx with moistened gauze.A good light source is needed in the form ofbright overhead lighting or a laryngoscope sinceintubation in dogs is accomplished under directviewing of the epiglottis and the position of thetube in relation to it. A laryngoscope is advisablefor intubation of brachycephalic dogs. It is usual toinduce anaesthesia in the dog to a level which isjust adequate to allow the dog’s mouth to be heldopen without initiating chewing movements,yawning, or tongue curling. When thiopentalor propofol have been used for induction of anaesthesiaand the dog is swallowing when intubationis attempted, the depth of anaesthesia is toolight and more drug should be administered.Swallowing during intubation is normal duringketamine anaesthesia.The dog may be positioned in either sternal orlateral recumbency. In either case, the assistantmust hold the dog’s head and neck in a straightline with one hand holding the top jaw, thumb andforefinger either side of the jaw behind the canineteeth and holding the upper lips up and awayfrom the teeth to facilitate the anaesthetist’s view.The dog’s tongue is pulled rostrally to spread openthe larynx and is held either by the assistant or bythe anaesthetist in such a way as to protect it fromlaceration by the teeth (Fig. 15.9A). The blade ofthe laryngoscope is placed flat on the tongue withthe tip of the blade depressing the tongue at thebase of the epiglottis. In some dogs the epiglottismay be trapped behind the soft palate and must bereleased by using the tip of the endotracheal tubeto push the soft palate dorsally (Fig. 15.9 B,C). Thelubricated tube should be used to depress theepiglottis on to the tongue and to keep it herewhile the tube itself is advanced in front of the arytenoidcartilages into the trachea (Fig. 15.9D).Frequently, rotating the tube 90° about its longitudinalaxis as the tip passes through the larynxallows the tube to be advanced more easily into thetrachea. A strip of gauze should be tied tightly tothe tube within the mouth just behind the canineteeth and then either around the jaw or behind thedog’s head (Fig. 15.10). The knot around the tubemust be tight to avoid slipping and accidentalextubation. The endotracheal tube cuff should beinflated with just enough air to prevent a leak that

THE DOG 413FIG.15.10 Endotracheal tube secured in place by a tie placed tightly around the connector and then tied around theupper jaw behind the canine teeth.Note that the tube has been shortened so that the expiratory valve is at the nostrils,ensuring minimum dead-space.The inflating tube for the cuff has been doubled over and sealed by a disposable needle case(alternatively a 3-way tap can be used).can be detected when listening for air escapingaround the tube during inflation of the lungsby squeezing the reservoir bag to a pressure of20–25 cm H 2 O with any ‘pop-off’ valve screweddown. The anaesthetist must remember to releasethe valve after this procedure.The process of intubation should be performedgently to avoid trauma to the pharynx and larynxwhich can cause tissue swelling and may resultin airway obstruction during recovery from anaesthesia(even necessitating tracheotomy).Furthermore, any time that the dog’s position orlocation is changed, the endotracheal tube shouldbe briefly disconnected from the breathing circuitto avoid twisting the tube within the trachea andtearing tracheal mucosa.HALOTHANE, ISOFLURANE, SEVOFLURANECardiovascular effectsIncreasing doses of all three agents cause significantdecreases in cardiac index, MAP, and meanpulmonary arterial pressure, a significant increasein CVP, and a slight decrease or increase in HR(Hoffman et al., 1991; Hysing et al., 1992). Responsesin MAP, mean pulmonary arterial pressure,and CVP vary considerably between individualdogs. In some studies the decrease in CO is lessduring deep isoflurane anaesthesia than at equipotentconcentrations of halothane (Hysing et al.,1992). Changes in cardiovascular parametersinduced by sevoflurane anaesthesia are most similarto those produced by isoflurane (Mutoh et al.,1997). Nonetheless, since all three agents decreasecardiovascular function, excessively low MAP willoccur during inhalation anaesthesia in hypovolaemicdogs (Pascoe et al., 1994).Halothane increases the sensitivity of themyocardium to catecholamines and prematureventricular depolarizations may develop in thepresence of hypercapnia. The prevalence of abnormalventricular rhythms may increase in animalswith myocardial ischaemia caused by thoraciccontusions and gastric dilatation/volvulus. Incontrast, sensitivity of the myocardium is notincreased by isoflurane or sevoflurane. Occasionally,conscious dogs with ventricular prematuredepolarizations maintain a more stable cardiacrhythm when anaesthetized with isoflurane.

414 ANAESTHESIA OF THE SPECIESIsoflurane, but not halothane, has antifibrillatoryeffects in atrial tissue (Freeman et al., 1990).In healthy dogs without significant cardiovasculardisease, the effects of the inhalation agentson cardiovascular function are relatively unimportantuntil deep anaesthesia is produced. Theimpact of inhalation anaesthesia must be consideredin animals with ischaemic heart disease andcardiomyopathy. Myocardial blood flow is increasedduring isoflurane anaesthesia (despitedecreased CO and MAP) and decreased duringhalothane anaesthesia (Gelman et al., 1984). Themyocardial depressant effects in dogs are comparablebetween isoflurane and sevoflurane, however,isoflurane causes coronary vasodilation whereassevoflurane decreases coronary blood flow withno change in coronary vascular resistance (Tomiyasuet al., 1999). Thus isoflurane is a coronaryvasodilator with potential beneficial (increasedmyocardial blood flow) and hazardous (‘coronarysteal’) effects. ‘Coronary steal’ occurs when bloodflow is redirected away from ischaemic myocardium.This may occur during isoflurane anaesthesiasince this agent causes dilation of normal myocardialarteries, preferentially the smaller coronaryresistance vessels than the larger conductive vessels,and this may divert blood from stenotic ordamaged arteries that are unable to dilate (Merin& Johns, 1994). The significance of the differencesbetween the agents on myocardial blood flow isnot as yet resolved. Many dogs with cardiovasculardisease are anaesthetized satisfactorily withisoflurane with no untoward postoperative consequences.It may be a wise precaution to use ananaesthetic protocol that relies heavily on opioidsfor analgesia and only low doses of isoflurane indogs with serious cardiac disease.Both halothane and isoflurane increase cerebralblood flow, decrease portal blood flow, and preserverenal blood flow (Gelman et al., 1984;Bernard et al., 1991). Isoflurane increases hepaticblood flow whereas halothane decreases it duringdeep anaesthesia.VentilationThe decrease in ventilation during inhalationanaesthesia in healthy dogs is unpredictable. Insome dogs, particularly small dogs and brachycephalicbreeds, breathing may be fast and shallow(panting). This rapid rate must not be mistaken fora light plane of anaesthesia, although sometimesthe tidal volume is so inadequate that uptake ofhalothane is insufficient to maintain anaesthesia.Hypoventilation will occur during deep inhalationanaesthesia and is very likely to occur in old dogs,obese dogs, and dogs receiving opioids.Sevoflurane and compound ASevoflurane reacts with soda lime and generatesseveral degradation products, of which compoundA is reported to be nephrotoxic. Since the concentrationof compound A is greater in circle circuitsusing low oxygen flows there has been concern forpatient safety when using sevoflurane in closedcircuit or low flow systems. In a clinical trial ofsevoflurane in dogs involving three UniversityTeaching Hospitals no evidence of impaired renalfunction was detected when the O 2 inflow wasmaintained at 500 ml/min (Branson et al., 1997).Concentrations of compound A measured in circlecircuits administering low-flow (< 15 ml/kg/min)sevoflurane to dogs were substantially lower thanthe concentrations reported to cause renal toxicosesin rats (Muir & Gadawski, 1998).AdministrationHalothane, isoflurane, and sevoflurane are potentinhalation agents that can be used to change thedepth of anaesthesia rapidly. Anaesthesia can beinduced with these agents through a facemaskfollowing preanaesthetic sedation with a sedativeor sedative/opioid combination or they can beused for maintenance of anaesthesia after inductionwith an injectable anaesthetic agent.Induction of anaesthesia by facemask is faster andsmoother with sevoflurane than isoflurane and,unlike isoflurane, sevoflurane does not cause airwayirritation. The concentration of agent requiredto maintain anaesthesia is usually between 1.0 and1.5 MAC values. Values reported for MAC varyslightly but are approximately 0.9% for halothane,1.4% for isoflurane, and 2.1% for sevoflurane.Occasionally, the anaesthetic agent for maintenancemay be changed from halothane to isoflurane,for example, in the face of increasing

THE DOG 415frequency of ventricular arrhythmias or when thesurgical procedure is unexpectedly prolonged andthe anaesthetist wishes to take advantage of theshorter recovery time of isoflurane. Elimination ofhalothane takes longer than uptake of isofluranebecause up to 20% of an inhaled dose of halothaneis retained for metabolism in the liver. However,isoflurane is less potent than halothane and a highervaporizer setting is required for the same depthof anaesthesia. A compromise is achieved by turningoff the halothane vaporizer and turning on theisoflurane vaporizer to the identical setting forabout 20 minutes, after which the vaporizer mayhave to be increased slightly to maintain the samedepth of anaesthesia.RecoveryIn contrast to halothane, almost none of theinhaled isoflurane or sevoflurane is retained formetabolism. Consequently, recovery from anaesthesiacan be very fast and complete unlessunderlying sedation is present or an opioid isadministered for postanaesthetic analgesia.NITROUS OXIDEIt is generally agreed that dogs cannot be anaesthetizedwith unsupplemented mixtures of N 2 Oand O 2 . N 2 O is used in non-rebreathing or circlecircuits either:1. As a vehicle for the vaporization and deliveryof volatile anaesthetic agents and as a mild analgesicsupplement to inhalation anaesthesia. The proportionof O 2 in the mixture must be at least 30%;[or:]2. In conjunction with injectable agents andanalgesic supplements, such as fentanyl, and withmuscle relaxants, for maintaining a light planeof anaesthesia. The percent of N 2 O should beapproaching 70% since it plays an important partin maintaining unconsciousness. Gas flow intoa circle must be sufficiently high to wash out N 2and allow N 2 O concentration to increase. The cuffon the endotracheal tube must be inflated toachieve an airtight seal and prevent dilution ofthe inspired gases with air. As stated earlier, N 2 Oshould not be utilized in a low-flow system unlessan O 2 analyser is incorporated in the breathingsystem.N 2 O is a useful adjunct to anaesthesia withhalothane, isoflurane, or sevoflurane, providingsufficient analgesia is given to maintain an uninterruptedcourse of anaesthesia. N 2 O will blockpatient response to intermittent intense surgicalstimulation such as traction on the ovaries, clampingof the spermatic cord, or the manipulationinvolved in reducing a long bone fracture. Inclusionof N 2 O allows a reduction in the concentrationof volatile anaesthetic agent and, therefore,MAP remains at an acceptable value.ARTIFICIAL VENTILATION OF THE LUNGSControlled ventilation (IPPV) may be needed tocorrect hypoventilation especially in overweightor geriatric dogs, dogs with depressed ventilationfrom administration of opioids or high concentrationsof inhalant anaesthetics, or for dogs withimpaired ventilation from positioning for perineal,back, or upper abdominal surgery. SometimesIPPV is indicated in treatment of a moderatedegree of anaesthetic-induced hypoventilationthat is resulting in an inadequate uptake of inhalationalanaesthetic and a depth of anaesthesia thatis too light for the medical or surgical procedure tobe performed. IPPV will be required in dogs forintrathoracic surgery, during neuromuscularparalysis, in neurological procedures that eitherinclude muscle weakness or dictate the need fordecreased intracranial pressure, and for respiratoryor cardiac resuscitation.O 2 or O 2 /N 2 O gas flow rates do not need to bechanged at the onset of IPPV. When IPPV is neededto decrease hypercapnia but no change in thedepth of anaesthesia is desired, the vaporizer settingshould be decreased by 20–25% at the onset ofIPPV to adjust for the increase in alveolar ventilationand anaesthetic uptake. When a circle circuitwith a vaporizer inside the circle is being used, thevaporizer setting should be decreased to almostoff, as the positive pressure generated in the circuitand the increase in gas flow through the vaporizercan result in a dramatic increase in inspired anaestheticconcentration, with potentially fatal consequences.

416 ANAESTHESIA OF THE SPECIESRegardless of the spontaneous respiratory rateof the dog, satisfactory arterial carbon dioxide tension(PaCO 2 ) can be achieved in dogs with IPPVincorporating a respiratory rate of 12 breaths/minwith a tidal volume of 15 ml/kg body weight, or20 breaths/min with a tidal volume of 10 ml/kg. Atidal volume of 15 ml/kg can be achieved inhealthy dogs with a peak inspiratory pressure of18 to 20 cmH 2 O, as observed on the pressuregauge of the Bain or circle circuits. Inspiratory timeshould be kept short and less than 2 s. These valuesmay have to be adjusted for the individualpatient so that for an overweight dog, for example,the tidal volume should be calculated on the dog’sideal weight since the contribution of fat to CO 2production is minimal. In contrast, the tidalvolume for an athletic or lean dog with a largeframe and minimal fat should be increased from15 to 20 ml/kg. The inspiratory pressure may be aslow as 15 cm H 2 O in tiny, thin dogs or may have tobe increased up to 35 or 40 cm H 2 O to achieve anadequate tidal volume in dogs with pressure onthe diaphragm, such as from increased intraabdominalfat or positioned in a prone head-downposition. Inspiratory pressure should be limited to25 cm H 2 O in dogs with pulmonary disease or contusionsto decrease the risk of barotrauma andpneumothorax. The chest of the dog shouldalways be observed to confirm inflation of thelungs in the inspiratory phase of the IPPV cycle.Assessment of the adequacy of IPPV can be precisewith arterial blood gas measurement andreasonably so with end-tidal CO 2 measurement.Without these, an approximate guide can be obtainedfrom observation of the inspiratory pressureon a pressure gauge in the breathing circuit andfrom the amplitude of chest excursion. Observationof mucous membrane colour provides noinformation about PaCO 2 . The occurrence of spontaneousrespiratory movements during the applicationof IPPV in a dog with pink mucousmembranes usually, although not invariably, indicatesthat hypoventilation is still present. Othercauses that should be considered are failure toexpand the lungs owing to a leak at the level of theendotracheal tube or to pneumothorax, hypoxaemia,hyperthermia, or inadequate analgesia.General considerations applying to IPPV in allanimals are given in Chapter 8.NEUROMUSCULAR BLOCKINGAGENTSMuscle relaxation can be achieved during anaesthesiaby inducing deep general anaesthesia, byincorporation of agents that induce central relaxation,such as medetomidine, diazepam, ormidazolam, or by use of agents that induce neuromuscularblockade. Use of neuromuscular blockingagents provides profound relaxation whilepermitting a reduction in dose rate of generalanaesthetic agents and consequently the anaestheticprotocol results in less cardiovasculardepression. Neuromuscular blockers are commonlyused for ocular surgery, ensuring a centraleye position to facilitate the surgical procedure.Further, relaxation of the extraocular musclesdecreases intraocular pressure – a prerequisite forintraocular surgery to avoid prolapse of the vitreous.These drugs are also used during anaesthesiafor thoracotomy to control the respiratory movementsand for abdominal surgery to fully relax theabdominal muscles and increase surgical exposureto the organs. The relaxation induced by neuromuscularblocking agents means that the surgeonneeds to use much less forcible retraction of musclesto gain access to the body cavities and so causesfar less bruising of muscles, greatly contributing toreduction in postoperative pain. These drugs mayoccasionally be necessary to facilitate surgicalreduction of a fractured long bone or a dislocatedhip. The use of neuromuscular blocking agentsand their general pharmacology has been consideredin Chapter 7.When neuromuscular blocking agents are used,facilities for IPPV must be available because effectivespontaneous respiratory movements are abolished.Monitoring depth of anaesthesia may bedifficult when breathing and palpebral reflex areabolished. When excessive anaesthetic administrationoccurs, there is increased risk of hypotensionand prolonged recovery from anaesthesia.Insufficient anaesthesia results in awareness,increased sympathetic nervous system stimulationand increased intraocular pressure. One approachis to anaesthetize the patient and to achieve a stableplane of anaesthesia before administration ofthe relaxant. Subsequently, vaporizer settings and

THE DOG 417oxygen flow rates are used that in the anaesthetist’sexperience result in an adequate depth ofanaesthesia. In dogs, signs of autonomic stimulationlisted below may be observed in response toinadequate anaesthesia or analgesia:1. Pupillary dilation2. Salivation3. Tongue twitch4. Increased heart rate and blood pressure.Agents usedThe agents most commonly used at present to produceneuromuscular block in dogs are listed inTable 15.6. Other agents used less frequently aresuxamethonium (succinylcholine), cisatracurium,doxacurium, and rocuronium. The dose ratesgiven have been found to be clinically effective butindividuals may vary in the dose required to inducea complete block. Further, a dose one-fifth ofthe dose used to produce total paralysis may beused for intraocular surgery because the extraocularmuscles are paralysed earlier (at lower dosage)than muscles of the abdomen or thorax. At theselow dose rates some respiratory movements maycontinue but alveolar ventilation is inadequate andIPPV should still be employed (Lee et al., 1998).TABLE 15.6 Neuromuscular blocking agents indogs. Approximate doses and indications for useAgent Dose Effective Indication(mg/kg) duration for use(min.);halothanePancuronium 0.06 40 Abdominaland thoracicsurgeryPancuronium 0.01 60 Central eyeposition forocular surgeryAtracurium 0.5 40 Abdominaland thoracicsurgeryAtracurium 0.1 25 Central eyeposition forocular surgeryVecuronium 0.1 25 Abdominaland thoracicsurgeryWhen the duration of neuromuscular blockmust be extended beyond one dose, subsequentinjections for top-up should be one-half of the initialdose approximately every 20 minutes. Continuousinfusion of agent will produce a moreconsistent blockade. Maintenance of block withatracurium requires 0.5 mg/kg/h after an initialbolus dose of 0.5 mg/kg with halothane anaesthesia(Jones & Brearley, 1987). Two infusion rates forvecuronium have been recommended: an initialbolus of vecuronium 0.1 mg/kg followed by aninfusion of 0.1 mg/kg/h (Jones & Young, 1991)and an initial bolus of 0.05 mg/kg with an infusionof 0.054 mg/kg/h (Clutton, 1992). The higher doserate was antagonized with intravenous injectionsof atropine and neostigmine, 0.05 mg/kg, and thelower infusion rate was reversed with atropineand edrophonium, 0.5 mg/kg.As described in Chapter 7, other factors influencethe duration of neuromuscular block.Pancuronium and vecuronium will have a prolongedduration of action in dogs with hepatic orrenal disease. Atracurium is spontaneouslydestroyed in plasma (Hofmann elimination) and isdetoxified independently of hepatic or renal function.Atracurium, but not pancuronium or vecuronium,may occasionally result in histamine releaseand a decrease in arterial blood pressure.Suxamethonium (succinylcholine) is a depolarizingneuromuscular blocking agent that causesinitial muscle fasciculation after injection andbefore the onset of paralysis. Suxamethonium,0.3–0.4 mg/kg, will produce about 20 minutes ofparalysis in dogs. Salivation and bradycardia maybe induced such that prior administration of ananticholinergic is advisable. There is no reversalagent for suxamethonium available but its actionusually terminates rapidly and completely.Termination of neuromuscular blockAs the effects of neuromuscular block wear off,assuming the anaesthetic depth to be that of lightsurgical anaesthesia, the dog’s eyes, which havebeen central, start to rotate downwards andspontaneous respiration returns. It can usually besafely assumed that once spontaneous breathingbecomes adequate that neuromuscular block willnot become re-established unless a further dose of

418 ANAESTHESIA OF THE SPECIESrelaxant is given. Administration of an aminoglycosideantibiotic during recovery from anaesthesiamay potentiate residual neuromuscular blockadeand result in re-paralysis.Neostigmine and edrophonium are commonlyused anticholinesterase antagonists of nondepolarizingneuromuscular block in dogs. Theresponse to a reversal agent varies considerablywith the degree of block present and should onlybe attempted when the block begins to wane.When full paralysing doses are given, the timelapse from last administration of vecuroniumshould be 10–15 minutes or 25–40 minutes for pancuroniumand atracurium. When the train-of-fourtwitches are being monitored with a peripheralnerve stimulator, at least two twitches should bepresent before attempting to reverse the block. Inthe absence of this monitoring, decreasing chestcompliance, attempts at spontaneous breathing orresponse to stimuli afforded by movement of theendotracheal tube in the trachea should beobserved before attempts are made to restore normalneuromuscular transmission. It should beremembered that respiratory acidosis prolongsthe action of most non-depolarizing relaxantsand will impair reversal by neostigmine. IPPVshould, therefore, be continued during the reversalprocess. Monitoring of neuromuscular blockshould be continued until all four twitches of thetrain-of-four are of equal strength. Inhalationanaesthesia is usually continued through thereversal process so that the patient is still lightlyanaesthetized when neuromuscular function isrestored.An anticholinergic drug such as atropine,0.02 mg/kg, or glycopyrrolate , 0.005 mg/kg,should be given i.v. 1–2 minutes before administeringthe anticholinesterase to block the adverseeffects of bradycardia, salivation and increasedintestinal motility. HR should be monitored and arepeat dose of anticholinergic given if necessary.Alternatively, the anticholinergic can be mixedwith neostigmine in the same syringe (1.2 mgatropine or 0.5 mg glycopyrrolate to 2.5 mg neostigmine)and the mixture injected i.v. in small incrementsuntil satisfactory reversal is achieved. Thedose of neostigmine varies from 0.01 to 0.10mg/kg,with a maximum total dose of 0.1 mg/kg. The doseof edrophonium is 0.05 to 0.10 mg/kg. Onset ofaction of neostigmine is slower than edrophoniumand may take several minutes.Residual neuromuscular block may remaineven after restoration of apparently normal breathing.In the dog, this is shown by the eyes remainingcentral with an absence of palpebral reflexes whateverthe depth of anaesthesia. Pharyngeal andlaryngeal reflexes may remain weak and airwayobstruction may develop after tracheal extubation.The dog must be closely observed for evidenceof residual block and inability to raise its headand protect the airway during recovery fromanaesthesia.When the low doses of relaxant are employedfor ocular surgery, administration of an anticholinesterasemay be unnecessary when only oneor two doses are given and the duration of surgeryexceeds an hour after last administration.ANAESTHETIC MANAGEMENTMAIN CONSIDERATIONSPositioningCare should be taken when positioning the animalto pad parts of the body that might be subject topressure ischaemia. Limbs should not be allowedto hang off the side of the table. Some positionswill compromise abdominal movement and contributeto hypoventilation. Access to the head formonitoring may be facilitated by placing a drapestand in front of the animal. A drape stand can beeasily created by bending a metal rod into a semicircle,with the diameter of the circle as wide as theoperating table, and 15 cm at each end bent at rightangles and parallel to the table edges for taping thestand to the operating table.Fluid therapyAll paediatric, geriatric, and sick dogs, and all thatwill be anaesthetized for more than an hour,should receive balanced electrolyte solution intravenouslyduring anaesthesia. Indeed, it may bepreferable for all anaesthetized animals to be givenfluid to maintain blood volume and transport ofanaesthetic agents to detoxification sites, therebyfacilitating recovery from anaesthesia. An appro-

THE DOG 419priate rate of infusion for most patients is 10 ml/kgbodyweight/hour. The infusion rate should behalved after 3 hours for patients that do not have abody cavity open or when blood loss is minimalbecause from this point haemodilution will develop.Accurate infusion of the volume of fluid invery small patients is essential and may be accomplishedby using a paediatric administrationset delivering 60 drops/ml, or by using a dropcounting pump or a syringe driver (Fig. 15.8), orsimply by hand delivery of small boluses of fluidfrom a syringe. Patients with low blood glucoseor who are at risk for hypoglycaemia shouldin addition be given 5% dextrose in water at 3 to5ml/kg/h.TABLE 15.7 Causes of hypotension duringanaesthesiaDecreased venous Decreased myocardialreturncontractility● Airway obstruction ● Anaesthetic drugs● Blood loss ● Adjunct drugs,e.g.antibiotics● Mechanical compression ● Arrhythmias,e.g.of caudal vena cava by ventricular prematuresurgeon or enlarged depolarization andorganatrial fibrillation● Pancreatic enzymes ● Hypercapniareleased during surgeryfor pancreatitis● Tension pneumothorax ● Mediators of sepsis andendotoxaemiaMonitoringRoutine monitoring techniques have beendescribed in Chapter 2. It should be rememberedthat both respiratory rate and depth of breathingmust be observed during evaluation of ventilationand that mucous membrane colour is not an indicatorof adequacy of ventilation. A serious potentialconsequence of an anaesthetized animal breathingair is hypoxaemia. Monitoring blood O 2 saturationwith a pulse oximeter increases the safety of anaesthesiainduced and maintained with injectableagents. Halothane and isoflurane significantlydepress cardiovascular function and measurementof arterial blood pressure increases the safety ofinhalation anaesthesia.Analgesia supplementsSupplementation with additional opioid maybecome necessary during anaesthesia as the effectsof premedication wane. A rough rule of thumb isto administer the supplemental dose at one-thirdto one-half of the initial premedication dose.An alternative is to add a short acting opioid tothe protocol, such as fentanyl or alfentanil.Fentanyl can be administered as a bolus of 2 µg/kgevery 20 minutes or as a continuous infusion of0.2–0.7 µg/kg/min. Fentanyl may cause bradycardia,for which an anticholinergic may be given,and hypoventilation necessitating IPPV. An alternativeis to use supplements of alfentanil, 2–5µg/kg. The addition of N 2 O to the inspired gases,with or without an opioid, will often supply sufficientanalgesia to abolish the dog’s response to theprocedure.ComplicationsHypoventilation commonly occurs in dogs thatare overweight, old, sick, deeply anaesthetized,and those which have increased intra-abdominalpressure. Treatment is IPPV.Hypotension is a common complication thatdevelops during anaesthesia caused by decreasedvenous return and decreased cardiac contractility(Table 15.7). Initial treatment of hypotension duringanaesthesia involves decreasing anaestheticadministration and expansion of blood volumewith balanced electrolyte solution as a 10 to20ml/kg i.v. bolus. Mechanical causes of decreasedvenous return, such as a closed ‘pop-off’ valve on acircle circuit or compression of the caudal venacava by an enlarged organ such as the spleen,should be eliminated. Expansion of plasma volumeby infusion of hydroxyethylstarch (hetastarch)or plasma at 20 ml/kg over 30 min may beeffective in restoring ABP, especially in the patientwith low plasma protein concentration (Table15.8). Blood loss of up to 20% of blood volume maybe replaced by infusion of balanced electrolyte atthree times the volume of blood lost. In the eventof rapid blood loss, treatment with hypertonic(7.5%) saline at 4 ml/kg over 10 minutes shouldsustain cardiac output and blood pressure at

420 ANAESTHESIA OF THE SPECIESTABLE 15.8 Drug to increase cardiovascularperformanceDrug Indication Dose rateDopamine Hypotension, 2–7µg/kg/min of aadvanced 100µg/mlatrioventricular solution in 0.9%heart block, saline;cardiac arrest, 10–15µg/kg/minto increase renal for cardiac arrestblood flowDobutamine Hypotension 2–7µg/kg/min of a100µg/ml solution in0.9% saline;increaseto 10µg/kg/min inemergencyHetastarch Low plasma 10–20ml/kg overproteinat least 30minutesHypertonic Hypotension 4–5ml/kg over(7.5%) saline from haemorrhage 10minutesor endotoxaemia,for precautionssee textLignocaine Premature 1–2mg/kg up toventricular 10mg/kg overcontractions, 10 minutes;infusionventricular 0.02–0.02mg/kg/mintachycardia of a 1mg/ml solutionSodium Metabolic 1–1.5mEq/kg,bicarbonate acidosis repeated once;useformula mEq to beinfused = Base deficit× 0.3 × kgbodyweight givenover 60minutesacceptable values for about 1.5 hours. Meanwhile,additional therapy in the form of crystalloid solution,whole blood, packed red blood cells, oroxyglobin can be initiated. Hypertonic saline probablyshould not be given when the source of thebleeding cannot be controlled. An antihistamine,diphenhydramine, 2 mg/kg, is given before plasmaor blood transfusion to minimize the risk of ananaphylactic reaction, and transfusion shouldbe started slowly to allow an early detection ofa transfusion reaction. Although hemodilutionoccurs during fluid administration in the face ofhaemorrhage, measurement of haematocrit andtotal protein should be performed periodicallyduring anaesthesia in patients with considerableblood loss.Catecholamines used to improve cardiovascularfunction include dopamine, 2 to 7 µg/kg/min(100 µg/kg solution made by adding 50 mg ofdrug to 500 ml of 0.9% saline solution), or dobutamine,2 to 7 µg/kg/min (100 µg/100 ml solution)delivered using a paediatric administration set(60 drops/ml) for most dogs (Table 15.8). Dopamineis most effective in conditions of cardiacarrest or advanced atrioventricular heart block,and can be used to improve urine production.Dobutamine is best used for patients with cardiomyopathy,congestive heart failure, or who areat risk for ventricular arrhythmias. Both dopamineand dobutamine can be responsible for the appearanceof premature ventricular depolarizations,however, dopamine is metabolized to noradrenalineand this may increase the risk of abnormal cardiacrhythm. Ephedrine, 0.02 mg/kg, can be usedto increase ABP in dogs with excessive venodilation.An anticholinergic is only effective in increasingblood pressure when the heart rate is low.Ventricular arrhythmias not infrequentlydevelop during anaesthesia as a consequence ofmyocardial ischaemia following automobile trauma,or abdominal distension from gastric dilatation/volvulus,or from myocarditis or vasoactivemediators of sepsis. Management should includeruling out or treating hypoxia and hypercapnia.Treatment should be intravenous lignocaine whenthe ventricular premature depolarizations aremultifocal or sufficiently frequent to decrease cardiacoutput and blood pressure (Fig. 15. 11).Lignocaine 2% or 4% can be injected as an i.v. bolusat 1 mg/kg and repeated if ineffective. Additionallignocaine up to 8 mg/kg over 10 minutes can begiven to dogs if a lower dose is ineffective.Lignocaine can be given as a continuous infusionat 0.02 to 0.08 mg/kg/min. A 1 mg/ml solution oflignocaine can be prepared by adding 500 mg oflignocaine (25 ml of 2% or 12.5 ml of 4%) to 500 mlof 0.9% saline.POSTOPERATIVE MANAGEMENTCare of the dog in the immediate postanaestheticperiod should include allowing it to breathe 100%O 2 for about 10 minutes, or as long as seems appropriate,after discontinuing anaesthetic administration.Inhalation agents can severely depress

THE DOG 421FIG.15.11 This ECG was recorded from a Hound anaesthetized for surgical repair of intestinal rupture and abdominalherniation as a result of trauma.The trace shows two consecutive premature ventricular depolarizations that resulted in apulse deficit.The dog’s blood pressure progressively deteriorated and was sustained by treatment with hetastarch,plasma,dobutamine and lignocaine.The dog survived to go home.ventilation and this is masked when the animal isattached to high concentrations of O 2 in the anaesthesiasystem. Hypoxaemia may develop if theanimal is disconnected and made to breathe roomair when still deeply anaesthetized. O 2 should besupplied for at least 5 minutes after N 2 O is discontinuedto avoid diffusion hypoxia.Gastric reflux into the pharynx may occur anytimeduring anaesthesia but when it has occurredthe mouth must be cleaned before extubation andsuction of the nasal passages may be advisable.Gastric reflux into the oesophagus occurs morecommonly than is usually recognized (Raptopoulos& Galatos, 1995). In a series of 510 dogs theincidence of oesophageal reflux was 17% but thegastric contents reached the mouth only in 0.6%(3 dogs). Many factors may contribute to gastrooesophagealreflux. Intra-abdominal surgery isassociated with an increased frequency of refluxand oesophageal sphincter pressure is significantlydecreased at the end of surgery duringisoflurane anaesthesia at the time of suturing of theskin (Hashim et al., 1995). The incidence of gastrooesophagealreflux is significantly higher whenanaesthesia has been induced with propofol thanwith thiopental (Raptopoulos & Galatos, 1997).The information concerning the influence of preoperativefasting on the volume and acidity ofgastric fluid and the impact of anaesthetic combinationson lower oesophageal sphincter tone is notsufficiently definitive to make specific recommendationsto minimize gastric reflux.Before the dog regains consciousness, the urinarybladder should be expressed by abdominalpalpation or catheterized to avoid soiling of bandagesfrom urination in the cage during recovery.The volume of urine collected should be measuredor estimated to assess the adequacy of urine flowduring anaesthesia. Approximately 1 ml/kg/hof urine should have been produced. Whenthe volume is less, consideration should begiven to continuation of fluid therapy after anaesthesia.Blood should be collected from dogsthat have suffered blood loss for measurementof haematocrit and total protein concentration.Blood glucose should be measured in diabeticdogs, and those that are less than 3 months of ageor are thin.Rectal temperature should be measured andheat applied when the temperature is low. Thetemperature of animals frequently decreasesfurther after the end of surgery when the coveringdrapes are removed. Warming is highly effectivewhen using a device blowing hot air intopads placed over the animal (Bair Hugger,Augustine Medical Inc., Eden Prairie, Minnesota,USA).Oxygen supplementationO 2 therapy should be considered for dogs thathave trouble adequately oxygenating. An O 2chamber or baby incubator, if available, can beused to supply an inspired concentration of

422 ANAESTHESIA OF THE SPECIESTABLE 15.9 Placement of a nasal O 2 tubeSuppliesPlacement● Polyvinyl or rubber ● Measure tubefeeding 5F or 8F from medial canthus tonostril● Permanent pen ● Mark distance with penmarker● Lignocaine 2% ● Lubricate tube● Lubricant gel ● Push nose dorsally,● Haemostat forceps introduce tube dorsallyfor a few mm,thenmedially and ventrally● Suture±‘Superglue’ ● Suture at the nares,between the eyes,andon the forehead ± gluetube to hairFIG.15.12 Nasal tube for O 2 insufflation.a 40% inspired O 2 concentration and can be amore economical method of administration(Fig 15.12). A bleb of lignocaine can be injectedsubcutaneously at the site for suture placementbut is not needed when the nasal tube is insertedand secured before the animal regains consciousness(Table 15.9). O 2 is humidified by bubblingthrough sterile water and insufflated into thepatient at 100 ml/kg/min (Fig. 15.13). The oxygendelivery tubing should be secured to a collar ortape around the neck.AnalgesiaFIG.15.13 Oxygen flowmeter and humidifier for nasalinsufflation.40–60% O 2 and warm the animal at the sametime. Nasal administration of O 2 may achieveDisplay of pain during recovery from surgery maybe obvious or subtle and veterinarians differ widelyin their assessment of the degree of pain and intheir interpretation for the need for analgesia. Thesigns of pain in dogs may vary from excitement,vocalization, and mutilation of the painful area toshivering, reluctance to move, excessive salivationand pupillary dilation. Dogs may become aggressive,guard the painful site and avoid humantouch. There are individual and breed differencesin tolerance for pain and it is possible that sportingor working dogs are less likely to exhibit behaviourchanges to a noxious stimulus. Various typesof pain scoring scales have been described in anattempt to accurately detect severity of pain.To complete a visual analogue scale, the patientis observed for a specific behaviour and the

THE DOG 423TABLE 15.10 Examples of intramuscular doserates of opioids for analgesia in the earlyrecovery periodOpioid Dose rate Dosing interval(mg/kg) (h)Morphine 0.3–0.5 4Pethidine 2–3 2Oxymorphone 0.05–0.10 4Butorphanol 0.2–0.3 2Buprenorphine 0.006–0.010 4–6observer places a mark on a line on which theleft end represents no pain and the right end representsthe most pain possible. Use of a numericalrating scale is similar except that a numberis assigned to the behaviour where 0 representsnormal or preprocedural behaviour and 2 or 3represents abnormal behaviour (Conzemius et al.,1997; Holton et al., 1998; Firth & Haldane, 1999).Evaluations of pain scoring techniques have discoveredthat measurements of some clinical signs,such as heart rates and respiratory rates, do notaccurately reflect the severity of postoperativepain. Although combining scores from a variety ofobservations including activity, mental status, posture,vocalization, etc., can provide a reliableassessment of pain (Firth & Haldane, 1999), scoresfrom different observers may vary considerably(Holton et al., 1998).Plans for provision of analgesia should havebeen made before anaesthesia and whenever possiblea multimodal approach should be employedthat includes local nerve blocks with opioid or localanaesthetic solution. Parenterally administeredopioids should be given before consciousnessreturns. Examples of opioids for postoperativeanalgesia and dose rates are given in Table 15.10but adjustments should be made for the individualdog. A small dose of sedative or tranquillizermay be needed to potentiate the effect of theopioid, for example, acepromazine 0.025 mg/kgi.v., or medetomidine 1–2 µg/kg. Disadvantagesof the i.m. or i.v. routes of administration for opioidsinclude a variable degree of respiratory depression,even hypoxaemia, potential decrease inABP, and decreased effectiveness of the pharyngealand laryngeal reflexes, with increased risk foraspiration.Transdermal fentanyl patchA method of postoperative pain control that isgaining popularity in North America is the transdermalfentanyl patch (Chapter 4, p.97). Deliveryof fentanyl is proportional to the patch surfacearea and delivered fentanyl doses are 25, 50, 75,and 100 µg/hour. Appropriate dose rates in veterinarypatients are under investigation but currentusage is 25 µg/h for small dogs > 2 kg, 50 µg/hfor 10–20 kg dog, 75 µg/h for 20–30 kg dog, and100 µg/h patches for dogs >; 30 kg. The patchesshould be placed and covered so that the animalscannot remove them and ingest the contents.Measurement of plasma fentanyl concentrationshas determined that steady state plasma concentrationsare not achieved for 24 hours after patchapplication (Kyles et al., 1996; Egger et al., 1998).Consequently, the patch must be applied the daybefore surgery to provide some intraoperativeanalgesia. If the patch is applied at the end of surgery,another form of analgesia must be providedfor the first 12–24 postoperative hours. There isconsiderable individual variation in the analgesiaprovided by a fentanyl patch, and even when thepatch is applied sufficiently early, the analgesia isnot enough to prevent the dog experiencing theacute pain in the immediate postoperative period.Plasma fentanyl concentrations are sustained for72 hours but decline rapidly after the patch isremoved. Respiratory depression has not been anotable problem. The patch should be removed ifsigns of overdosage such as a restlessness, drowsiness,or inappetance are observed.SPECIFIC PATIENT PROBLEMSCARDIAC DISEASEGeneral recommendations for anaesthesia of dogswith cardiac disease include premedication topresent a calm, unstressed animal for induction ofanaesthesia and sufficient analgesia during andafter surgery. Management of cardiovascular functionmust include maintenance of an adequateblood volume without overload, preoxygenationand provision of O 2 during anaesthesia to avoidhypoxaemia, and adequate monitoring of the cardiovascularsystem during anaesthesia to detect

424 ANAESTHESIA OF THE SPECIESTABLE 15.11 Significance of cardiac disease toanaesthesiaPatient problem Anaesthetic considerationsMitral valve Increased risk forinsufficiency hypotension.Consider increasing cardiacpreload (i.v.fluids to maintainblood volume),avoiddecreasing cardiaccontractility,avoid bradycardia,and consider slightlydecreasing cardiac afterload(some vasodilation preferableto vasoconstriction)Cardiomyopathy Increased risk for hypotensionand death.Careful choice of anaestheticagents to avoid decreasedcardiac contractilityVentricular Increased risk for hypotensionarrhythmias e.g. or ventricular fibrillation andautomobile trauma,death.gastric dilatation Consider use of agentsvolvulusthat do not sensitize themyocardium tocatecholamines,e.g.benzodiazepines,opioids,ketamine,isofluranePatent ductus Increased risk for hypotensionarteriosus before ligation and forpulmonary oedema afterligation.Minimize dose of agents thatcause vasodilation and limitbaseline intraoperative fluidrate to 6 ml/kg/hunacceptable abnormalities. Different forms ofcardiac disease require specific management(Table 15.11). Knowledge of the physiology of thedisease can be used to define the pharmacologicalrequirements of the anaesthetic drugs.Mitral insufficiencyAnaesthesia for the old dog with mitral insufficiencymust take into consideration the impact ofold age on anaesthetic requirements and thatmitral insufficiency decreases cardiac output in thepresence of bradycardia, decreased venous return,and increased systemic vascular resistance.Consequently, premedication with glycopyrrolateis indicated and agents that should be avoidedinclude xylazine, medetomidine, large doses ofacepromazine, and thiopental.Patent ductus arteriosusA dog with a patent ductus arteriosus has lowdiastolic and MAP pressure and care should betaken with anaesthetic agents that cause vasodilation.Infusion of balanced electrolyte solution tothese patients should be restricted to 6 ml/kg/h,unless individual evaluation indicates need for amodified rate, to avoid pulmonary oedema afterligation of the ductus. ABP may be increased byinfusion of dobutamine, although a dramaticincrease in diastolic and mean pressures usuallyoccurs when the ductus is ligated. Other requirementsfor management relate to the thoracotomywhich is discussed later and in Chapter 19.ENDOSCOPYGastrointestinal endoscopyGastroduodenoscopy and proctoscopy may beperformed in relatively healthy dogs or in dogswith a history of chronic weight loss. In the lattercase, decreased serum total protein concentrationmay result in decreased anaesthetic requirementfor thiopental or propofol and serious loss of fatand muscle will result in prolonged recovery fromthiopental. Although the ease of introduction ofthe endoscope into the duodenum is directly relatedto the experience of the veterinarian in thisprocedure, premedication with atropine andmorphine has been documented to significantlyincrease the number of attempts to successfullypass the endoscope (Donaldson et al., 1993). Complicationsof endoscopy include excessive distensionof the stomach and intestines resulting in hypoventilationand gastric reflux into the pharynx. Thecardiovascular changes caused by gastrointestinaldistension depend on the severity of distension.Changes in ABP and CO are small during gastrointestinalendosopy in the majority of healthydogs (Jergens et al., 1995) but the anaesthetist mustbe alert for bradycardia and hypotension thatdevelop in individuals. Biopsy of the intestines

THE DOG 425carries the risk of perforation and tension pneumoperitoneumresulting in hypotension andthe need for an emergency exploratory laparotomy.Endoscopy for removal of an oesophageal foreignbody or for dilation of an oesophagealstricture also introduces the potential for pneumothorax.BronchoscopyBronchoscopy and bronchoalveolar lavage (BAL)are most difficult to manage in smaller dogs. Theability to cough should be retained during BALand this requires a light plane of anaesthesia witheither thiopental or propofol. Anticholinergicsshould be omitted to preserve the volume of secretionsand should not be used in dogs withpneumonia to avoid consolidating secretions.Butorphanol is marketed as an antitussive, however,it has proven to be a useful agent for premedicationin these dogs provided that the dose ofinduction drug is kept to a minimum. The drug forinduction should be administered in small incrementsto retain the coughing response to introductionof the sterile endotracheal tube and toinstillation of sterile saline for bronchial wash. Hypoxaemiais a common complication, especially duringbronchoscopy in a small dog where the diameterof the endoscope may be large in comparison withthe lumen of the trachea. Preoxygenation is essentialand use of a pulse oximeter is advisable duringthe procedure. O 2 may be supplied intermittentlyby facemask when the endoscope is removed orinsufflated around or down the endocope. Whenthe procedure is expected to last for more than afew minutes, anaesthesia may have to be continuedwith an injectable drug such as propofol.GASTRIC DILATATION/VOLVULUSSYNDROMEAbdominal distension resulting from gastricdilatation and volvulus (GDV) decreases CO andABP. Experimental investigations of GDV havedocumented a 64% decrease in CO (Orton &Muir III, 1983) or as much as an 89% decrease associatedwith 50% decrease in coronary blood flow(Horne et al., 1985). Even when the stomach hasbeen decompressed before anaesthesia, myocardialischaemia increases the risk of hypotensionand poor organ perfusion during anaesthesia.Overt clinical signs of myocardial ischaemia suchas cardiac arrythmias may not appear until afteranaesthesia has been induced or even after surgeryhas been completed. Forty percent of dogs withGDV or gastric dilatation develop cardiac arrhythmias,mainly ventricular premature depolarizationsor ventricular tachycardia, between 12 and 36hours after the onset of the problem (Muir, 1982;Brockman et al., 1995).Gastric decompression should be accomplishedbefore induction of anaesthesia by passage of astomach tube. Blood volume should be expandedwith crystalloid solution administered intravenouslyup to 90 ml/kg in the first hour.Hypertonic (7.5% saline solution) saline, 4 ml/kgi.v. over 10 minutes, will induce a more rapidimprovement in cardiovascular function. Hypertonicsaline in 6% Dextran 70, 5 ml/kg, has alsoproven to be effective (Allen et al., 1991; Schertelet al., 1997). Further volume expansion canbe achieved by administration of hetastarch,20 ml/kg. Reperfusion injury may occur afterdecompression of the stomach. Deferoxamine30mg/kg i.m. (Desferal, Novartis, East Hanover,New Jersey, USA), which inhibits production ofhydroxyl radicals, given before anaesthesia mayincrease survival rate (Lantz et al., 1992).Routine administration of sodium bicarbonateis not recommended because of uncertainty of thedog’s metabolic status. Gastric sequestration mayresult in metabolic alkalosis, however, hypotensionand decreased peripheral perfusion mayresult in metabolic acidosis. Treatment of suspectedmetabolic derangements are best reserved untilpH and blood gas analysis can be performed.Dogs with gastric necrosis are likely to have abnormalhemostatic function, most frequently thrombocytopeniaand decreased antithrombin IIIactivity, and a proportion will develop disseminatedintravascular coagulation (DIC) (Millis et al.,1993).Anaesthetic management of GDVThe clinical status of these dogs before anaesthesiavaries from relatively healthy to moribund.Anaesthetic agents, dose rates and additional

426 ANAESTHESIA OF THE SPECIESTABLE 15.12 Significance of hepatic disease to anaesthesiaPatient problemDecreased hepatic functionPortosystemic shuntBile duct calculiAnaesthetic considerationsIncreased risk for excessive bleeding,hypoglycaemia,prolonged recovery fromanaesthesia.Consider checking coagulation profile before anaesthesia (may need freshplasma),monitoring blood glucose and giving 5% dextrose in water 3 ml/kg/h aspart of fluid therapy,using anaesthetic agents that are easily eliminated orantagonized.During anaesthesia,avoid further hepatic damage by preventing hypotension andhypercarbiaIncreased risk for hypotension,hypoglycaemia,and hypothermia.Benzodiazepines contraindicated with encephalopathy;use agents with minimalcardiovascular depressant effects and that can be antagonized or do not dependon hepatic function for elimination.During anaesthesia,give 5% dextrose in water 3 ml/kg/h as part of fluid therapyand treat hypotension with dopamine or dobutamineIncreased risk for surgical procedure to cause hypoventilation and hypotension(mechanical obstruction of venous return).Contraction of bile ducts may be initiated by opiates.Impact of partial agonistsunder debatemanagement will have to be adjusted to theindividual dog and administered bearing in mindthat the dog may have severely decreased anaestheticrequirements.Cardiovascular monitoring should begin beforeinduction of anaesthesia by attaching ECGleads or a form of indirect or direct blood pressuremeasurement. Preoxygenation is advisable byadministration of O 2 by facemask for severalminutes before induction. Two induction techniquesthat are preferable for dogs with GDVare diazepam/ketamine and neuroleptanalgesia.A suitable alternative technique (except forthe high expense) is to use etomidate which preservescardiovascular function. Thiopental andpropofol are less appropriate as these agentsdecrease CO to a greater extent. Because of the riskof regurgitation and aspiration mask induction isinadvisable .Induction of anaesthesia with i.v. diazepam,0.25 mg/kg, and ketamine, 5 mg/kg, preservescardiovascular function. Tachycardia caused bythese drugs may potentiate ventricular arrhythmiasand i.v. lignocaine, 2 mg/kg, can be givenbefore or after ketamine to control abnormalrhythms. After the airway is secured analgesia canbe supplemented with an opioid. An alternativeinduction technique is neuroleptanalgesia. Thecombination of diazepam and fentanyl, ordiazepam and oxymorphone will provideanaesthesia with minimal cardiovascular depression.Disadvantages of these techniques are vomitingand probable hypoventilation necessitatingIPPV. Anaesthesia can be maintained with aninhalation agent or by continuous infusion of anopioid.HEPATIC DISEASEAdministration of anaesthesia to dogs withdecreased hepatic function presents two difficulties.First, recovery from anaesthesia will be slow ifthe anaesthetic agents used must be detoxified bythe liver. Secondly, further hepatic damage canoccur during anaesthesia from hepatic hypoxia asa consequence of hypotension, splanchnic vasoconstrictionfrom hypercapnia, or arterial hypoxaemia.Dogs with moderate to severe hepaticdisease may have disorders of clotting and tests ofcoagulation should be performed before surgery.Hypoglycaemia is also a potential complicationand 5% dextrose in water should be infused duringanaesthesia. Surgical problems relating to theliver, such as portosystemic shunt and bile ductcalculi, have specific anaesthetic considerations(Table 15.12).

THE DOG 427TABLE 15.13 Significance of neurological diseaseto anaesthesia (ICP = intracranial pressure)Patient problemNEUROLOGIC DISEASEDogs with neurologic disease range from beingessentially healthy to comatose. Anaesthesia maybe straightforward, or the dog may be at risk ofanaesthetic overdose or serious neurologic consequencesfrom increased intracranial pressure(Table 15.13). Diagnostic procedures, such ascollection of cerebrospinal fluid (CSF), myelography,or magnetic resonance imaging (MRI) havespecific considerations relating to anaesthesia.Increased intracranial pressureAnaesthetic considerationsSeizuresAvoid acepromazine.Use agents that decrease ICPe.g.thiopental,propofol,etomidate,diazepamDepression,decreased Adjust dose rates formentation,meningitis decreased anaestheticrequirementIncreased ICP,e.g. Use agents that decreasebrain tumour, ICP.hydrocephalushead traumaUse controlledventilationto prevent hypercarbiaDogs with increased intracranial pressure (ICP)before anaesthesia can be treated with methylprednisolonesodium succinate and mannitol.Anaesthesia may be induced with a combinationof agents known to decrease ICP and cerebralmetabolic O 2 demand, such as diazepam, midazolam,thiopental and propofol. Halothane andisoflurane are usually used to maintain anaesthesiaeven though they increase ICP by increasingcerebral blood flow and causing hypercapnia.Hypercapnia has a direct effect on cerebral vasculaturecausing increased cerebral blood flow thatincreases ICP. Consequently, IPPV should be usedthroughout anaesthesia in dogs with increasedICP (e.g those suffering from hydrocephalus, braintumours, or head trauma). IPPV should also beinstituted during collection of cerebrospinal fluid,as increased ICP during this procedure may resultin cerebellar herniation. Hypertension must beavoided as it also increases ICP. Acepromazine isusually avoided in dogs at risk for seizures as itdecreases the seizure threshold.MyelographyDogs must be observed closely for mild to seriousadverse side effects during injection of iohexol formyelography. Respiratory arrest should be treatedby IPPV and hypotension by decreasing anaestheticadministration. Severe decreases in ABP may betreated with dopamine or dobutamine. Occasionallycardiac arrest ensues. Balanced electrolyte solutionshould be infused during anaesthesia at a rateof 10 ml/kg/hour to promote excretion of the contrastagent. The dog’s head must be supported in anelevated position after the myelogram to encourageflow of contrast agent from the brain. Recoveryfrom anaesthesia for myelography may be complicatedby seizures requiring specific treatment.ORTHOPAEDIC SURGERYGeneral considerations for anaesthesia fororthopaedic surgery include awareness of the specificproblems created by a traumatic accident.Prolonged anaesthesia, significant blood loss, provisionof analgesia, and hypothermia are commonproblems for anaesthetic management. Analgesiafor surgery on the forelimb can include, in additionto parenteral administration of opioid andNSAID, epidural block with morphine and, forsurgery distal to the elbow, brachial plexus nerveblock with bupivacaine. Analgesia for surgery ofthe hindlimbs and pelvis can include parenteralopioid and NSAID, and epidural nerve block withmorphine alone or with bupivacaine. An alternativeto epidural block for elective surgery of thestifle is intra-articular morphine or bupivacaine.Repair of a fractured jaw introduces the risk ofaspiration of blood and debris and care must betaken to ensure that the endotracheal tube cuff issufficiently inflated and that the mouth is cleanedbefore recovery from anaesthesia. Surgical repairmay require that the endotracheal tube beremoved from the oropharynx to increase exposureto the fracture and to enable the surgeon tojudge correct alignment and avoid malocclusion ofthe teeth. Anaesthesia is induced and orotracheal

428 ANAESTHESIA OF THE SPECIESFIG.15.14 The endotracheal tube has been inserted through a pharyngostomy incision to provide better surgical accessfor repair of the fractured mandible. A reinforced metal spiral endotracheal tube has been used to avoid kinking of thetube as it turns 180° within the pharynx.intubation is performed as usual. The site for apharyngostomy tube is clipped, the skin preparedfor surgery, and the pharyngostomy made withappropriate surgical technique. The endotrachealtube cuff is deflated and the tube is disconnectedfrom the anaesthetic system and tube adapter.First, the pilot balloon is grasped with the tip offorceps introduced through the pharyngostomyand pulled through to the outside, and then theoral end of the endotracheal tube is exteriorized.The endotracheal tube is reconnected to theadapter and anaesthetic system, the cuff inflated,and anaesthesia proceeds (Fig. 15.14). Use of anendotracheal tube with a metal spiral embedded inits wall will ensure that the tube does not becomekinked during placement or the surgical procedure.An alternative technique for pharyngostomyintubation is to introduce the endotracheal tubefrom the outside and to use forceps to grasp theend of the endotracheal tube inside the mouth todirect the tube into the larynx.decreased CO and ABP, and by causing sympatheticnervous system stimulation. Thus, dogswith chronic renal disease are at risk for acuterenal failure after anaesthesia. Adverse effectsof anaesthesia can usually be prevented by adequatefluid therapy during anaesthesia and choiceof an anaesthetic technique providing a rapidrecovery from anaesthesia. For some dogs, adequatefluid therapy should include starting infusionbefore anaesthesia and continuing fluidadministration at a reduced rate for some hoursafter anaesthesia.Acute renal failure from urethral obstruction orurinary bladder or ureter rupture includes problemsof hypovolaemia, azotemia, and metabolicacidosis, all of which result in decreased anaestheticrequirement and increased risk of hypotensionand arrhythmias. Intensive care before anaesthesiawill decrease complications occurring duringanaesthesia. Anaesthetic agents should be administeredat markedly decreased dose rates.RENAL DISEASEAnaesthesia and surgery decrease urine formationby decreasing renal blood flow throughTHORACOTOMYConsideration of the appropriate choice of anaestheticagents for the dog’s problems is essential to

THE DOG 429TABLE 15.14 Significance of renal disease toanaesthesiaPatient problem Anaesthetic considerationsChronic renal Increased risk for prolongeddisease recovery from anaesthesia andfurther deterioration of renalfunction after anaesthesia.Use a combination of anaestheticagents to facilitate low dose ratesand rapid elimination.Consider initiating diuresis withi.v.balanced electrolyte infusion10 ml/kg/h for 60 min beforeinduction of anaesthesia,preventhypotension during anaesthesia,monitor urine production,continue i.v.fluids into recoveryperiodUrethral Increased risk for anaestheticobstruction, overdose,hypoventilation,ruptured ureter, hypotension,and prolongedurinary bladder recovery from anaesthesia.or urethra Provide medical treatment beforeanaesthesia to expand bloodvolume and decrease serumpotassium to

430 ANAESTHESIA OF THE SPECIESspreads throughout the lungs resulting in hypoxaemia.The changes may be severe and progress toa fatal outcome.Monitoring ABP, HR and cardiac rhythm areof prime importance during thoracotomy.The dog’s problems, the anaesthetic agents, andsurgical manipulation can all cause hypotensionand arrhythmias. Cardiovascular performancemay have to be improved as previously described inthe section on anaesthetic management. Prematureventricular contractions or ventricular tachycardiamay need to be treated by i.v. lignocaine.Analgesia can be provided by systemic administrationof opioids, by regional analgesia fromintercostal nerve blocks with bupivacaine,interpleural instillation of bupivacaine (up to atotal dose of 2.5 mg/kg), and epidural analgesiawith morphine (0.1 mg/kg). Postanaesthetic ventilationand oxygenation should be monitored closelyand administration of O 2 by O 2 chamber ornasal insufflation (100 ml O 2 /kg/min) may berequired for several hours.The extent of postoperative care needed afterthoracotomy varies from case to case. Minimalcare may be necessary after repair of a patent ductusarteriosus, unless a complication occurredor the dog has heart failure, and similarly, formany ruptured diaphragm repairs. However,intensive care will be needed for dogs with complications,such as sepsis, persistent pneumothorax,continual fluid accumulation, or aftercomplicated surgery. Chest tubes not connected toan underwater drain or Heimlich valve should besucked avoiding excessive pressures, every 1–2hours initially, decreasing to every 4 hours,depending on the progress of recovery. Lavagewill be necessary when bacterial contamination ispresent.LOCAL ANALGESIALocal analgesia is frequently used as an adjunctto general anaesthesia or in the treatment of preorpostoperative pain and less frequentlyemployed as the sole method of analgesia for surgicalprocedures in dogs. The techniques for theseblocks, listed alphabetically, are described in thissection.FIG.15.15 Auriculopalpebral nerve block.The nerve isblocked just where the zygomatic ridge dips medially.SPECIFIC APPLICATIONSAuriculopalpebral nerve blockThe nerve runs caudal to the mandibular jointat the base of the ear and, after giving off the cranialauricular branch, proceeds as the temporal branchalong the dorsal border of the zygomatic archtowards the orbit. Before reaching the orbit thenerve divides into two branches, which pass mediallyand laterally to supply the orbicularis muscle.The needle is introduced through the skin andfascia over the midpoint of the caudal third of thezygomatic arch (just where the arch can be felt todip sharply medially) and up to 1 ml of 2% lignocaineis injected (Fig. 15.15). The blocking ofthis branch of the facial nerve does not produceany analgesia. By paralysing the orbicularismuscle it facilitates examination of, and operationson, the eyeball. It is of particular value in preventingsqueezing of the eyeball after intraocularoperations.Brachial plexus blockBlock of the brachial plexus will provide analgesiabelow the elbow. Injection can be made with theanaesthetized dog in lateral recumbency using a22 gauge 3.75 cm, 6.25 cm, or 8.75 cm long spinalneedle, according to the size of the dog. Bupivacaine,2.0–2.5 mg/kg, should provide at least6 hours of analgesia with an onset time of 10 to40minutes. Alternatively, lignocaine, 6 mg/kg, canbe used for a shorter duration of action – approxi-

THE DOG 431Point of shoulder/greater tubercleof humerus1st ribC6FIG.15.16 Landmarks for brachial plexus nerve block.mately 2 hours. The brachial plexus originatesfrom the ventral branches the 6th, 7th and 8th cervicaland the 1st and 2nd thoracic spinal nerveswhich form three cords which run for a short distancebefore segregating into the nerves of the thoraciclimb. Local anaesthetic solution must bespread over a wide area to block all the nerves.Commercially available solutions can be dilutedwith saline by 25% to produce a larger volume forinjection and increase the spread of anaesthetic.An area rostral to the cranial border of thescapula, between the point of the shoulder and thecervical vertebrae should be clipped and the skinprepared as for surgery. The point of the needleshould be inserted halfway between the point ofthe shoulder and the transverse process of the 6thcervical vertebra. It is then advanced medial to thescapula and parallel to the vertebral column to the1st or 2nd rib (Fig. 15.16). Aspiration before injectionof local anaesthetic is essential to ensure thatthe needle is not in a blood vessel. Part of the totalvolume is injected and the remainder injected asthe needle is withdrawn, aspirating before eachsubsequent injection.Some complications may occur as a consequenceof this procedure. Large blood vessels passthrough the area for injection and needle puncturemay create a large haematoma. Further, the localanalgesic solution may be injected intravascularly,the needle may enter the thorax and permit theentry of air into the pleural cavity, the brachialplexus may be damaged, causing neuritis or permanentparalysis, or infection may be introducedinto the axilla. However, if due care is exercised,the technique may be regarded as a relatively safeprocedure, of particular value for intraoperativeand postoperative analgesia or even one that canbe used as the sole anaesthetic agent for surgery.EPIDURAL BLOCKEpidural block with lignocaine or bupivacaine canprovide analgesia for major surgery of the hindlimbsand pelvis. Opioids, morphine, oxymorphone,fentanyl, sufentanil, and butorphanol havebeen used in the epidural space to provide analgesiaduring and after surgery, although othermethods of analgesia may be needed to manageacute pain in the immediate recovery period.Combinations of an opioid with bupivacaine orxylazine or medetomidine have been used toextend the duration of analgesia. Epidural block iscontraindicated if the dog has a coagulopathy orskin infection over the lumbosacral area.TechniqueThe technique of epidural block has already beendiscussed in Chapters 10 and 13. The spinal cordends in the dog at the junction of the sixth and seventhlumbar vertebrae, and the meninges continueto the middle of the sacrum. Not infrequently, aneedle inserted at the lumbosacral space penetratesthe dura and cerebrospinal fluid (CSF) is aspirated.The epidural injection may be performed with aconscious dog in the sternal or lateral positions butis usually performed with the anaesthetized dog inlateral recumbency. Sudden forceful movement inthe conscious dog in sternal position cannot effectivelybe prevented when the animal’s limbs arebeneath it. Better control is achieved by the assistantrestraining the dog holding the hocks forwardso that the hind limbs are in extension. The hairshould be clipped over a sufficient area to observethe landmarks for injection and to maintain sterility.The site for needle insertion is located by identifyingthe cranial dorsal iliac spines of the pelvis(Fig. 15.17). An imaginary line joining these crossesmidline over the dorsal spinous process of the lastlumbar vertebra. The lumbosacral junction is pal-

432 ANAESTHESIA OF THE SPECIESFIG.15.17 Site for epidural injection.This dog isanaesthetized and clipped for orthopaedic surgery. Animaginary line between the caudal dorsal iliac spinescrosses the midline at the lumbosacral space. Animaginary line between the cranial edges of the cranialdorsal iliac spines crosses the midline at the dorsal spinousprocess of the last lumbar vertebra.pated as a depression immediately caudal to thismidline prominence, adjacent to the caudal dorsaliliac spines, which in thin dogs can be seen as themost dorsal bumps of the pelvis. In heavily muscledor fat dogs and dogs with rounded hindquarters,the caudal dorsal iliac spines are difficult topalpate and heavy reliance is placed on identifyingthe spinous process of the last lumbar vertebra.Palpation of the spinous process of the previouslumbar vertebra can be used as a guide. The needleshould be inserted caudal to the last spinousprocess at a distance that is half of the distancebetween the two spinous processes.In conscious dogs an insensitive skin weal ismade with a fine needle and a bleb of local anaesthetic.A 21 or 22 gauge spinal needle, 3.75 cm forsmall dogs and 6.25 cm for large dogs, is insertedmidline perpendicular to the skin and to the curvatureof the rump (Fig. 15.18). Penetration of theinterarcuate ligament imparts a distinct ‘popping’sensation to the fingers. Should bone rather thanligament be encountered, it indicates that thedirection of the needle has been wrong and thatits point has struck an articular process or theroof of the first sacral segment. If this occurs theneedle is slightly withdrawn and a search madefor the space by redirecting it a little caudally, craniallyor laterally. The hub of the needle should beheld securely as the stilette is removed. A 3 mlsyringe containing 0.5 ml air should be attachedFIG.15.18 Epidural analgesia.The site and direction forinsertion of the needle.and, after aspiration has not drawn cerebrospinalfluid (CSF) or blood into the syringe, injection ofair should offer no resistance. Confirmation of correctplacement is made by ensuring that the needleis midline, that it is sufficiently deep (needleshould be supported securely by surrounding tissueswhen the tip is in the epidural space), that aslight resistance then penetration ‘pop’ is appreciatedduring traverse of the interarcuate ligament,and there is no resistance to injection of the air. IfCSF or blood are aspirated into the syringe, thesyringe should be disconnected, the stilette reinsertedand the tip of the spinal needle repositioned.Injection of the anaesthetic solution shouldbe made over 30 seconds to avoid an increase inintracranial pressure. The injectate should bewarmed before performing epidural analgesia inthe conscious dog to avoid movement in responseto the cold solution.A catheter can be introduced easily some 2–3 cminto the epidural space through a correctly placedTuohy needle (Fig. 15.19). This technique is usefulfor continuous postoperative analgesia.Drugs used in the epidural spaceLignocaine 2% with 1:200 000 adrenaline will produceanalgesia in 15 minutes and last 1.5–2.0hours. Bupivacaine 0.50% or 0.75% has a sloweronset of action at 20–40 minutes and a longer durationof at least 6 hours. To produce analgesia up toL1 a dose of approximately 1 ml per 4.5 kg bodyweight is required and for cranial laparotomieswhere analgesia is needed to the 4th or 5th thoracicsegment this dose is usually increased to about 1

THE DOG 433(Branson et al., 1993), or even as long as 23 hours(Bonath & Saleh, 1985). Analgesia may extend asfar forward as the forelimb and provides a significantdecrease in anaesthetic requirement for surgery(MAC value for halothane decreased by30–40%) (Valverde et al., 1989; Valverde et al., 1991).The duration of analgesia after epidural injection ofoxymorphone, 0.05 mg/kg, was measured at7.6hours after hindlimb orthopaedic surgery (Vesalet al., 1996) and 10 hours after thoracotomy(Popilskis et al., 1991). The anaesthetic requirementfor halothane is reported to be significantlydecreased after epidural administration of oxymorphone,0.1 mg/kg, and further by oxymorphonewith bupivacaine, 1 mg/kg (Torske et al., 1998).Epidural fentanyl and butorphanol have also beenused, but the duration of analgesia is short.Potential complicationsFIG.15.19 Epidural‘Minipack’ set (Portex Ltd) which isideal for the introduction of a catheter into a dog’sepidural space.The set contains a 10 ml syringe,19 GTuohy needle graduated 10–45 mm × 5 mm,open-endedcatheter marked at 20–100 mm × 10 mm from tip,loss-ofresistancedevice,flat filter and Luer Lock connector.ml per 3.5 kg. The dose should be decreased about25% in pregnant animals. In contrast, epiduralblock may not extend as far cranially as expectedin dogs that have experienced serious weight loss.Morphine, 0.1 mg/kg in a total volume of0.10–0.25 ml/kg (a preservative-free solution contains1 mg/ml), is the opioid used most frequentlyfor epidural injection in veterinary medicine.Morphine preparations containing phenol orformaldehyde should not be used whereas the preservativechlorbutanol has not been shown to beneurotoxic (Du Pen et al. 1987).The onset of analgesiais about 45 minutes and lasts from 6–12 hoursIn dogs, temporary interference with hindlimbmotor power is of no clinical consequence.Analgesia caused by local anaesthetic solution thatdiffuses into the thoracic segments may be accompaniedby hypotension that can be minimizedby infusion of balanced electrolyte solution, 10–20ml/kg, as the block develops. ABP and peripheralperfusion should be monitored throughoutand a catheter for infusion of fluid and vasoactivedrugs should they be needed must be placed in avein before epidural block is induced .In man, respiratory depression has been reportedto occur several hours after epidural morphineinjection, but this does not appear to be a problemin dogs. Oxymorphone is absorbed into the systemiccirculation rapidly with peak valuesattained within 15 minutes after administration,similar to absorption after intramuscular injection(Torske et al., 1999). Serum values of morphinepeak 30 minutes after epidural administration. Epiduraloxymorphone results in significant decreasesin HR and CO (Vesal et al., 1996; Torske et al., 1999).These effects can be satisfactorily improved byadministration of glycopyrrolate. ABP, HR and COare not depressed after administration of morphinein anesthetized dogs (Valverde et al., 1991). A caseof postoperative urinary retention was reported ina dog following epidural analgesia with morphineand bupivacaine (Herperger, 1998).

434 ANAESTHESIA OF THE SPECIESA clinically insignificant complication that maybe regarded most adversely by the owners of showdogs is inability of hair over the lumbosacralregion to grow back at the same rate as expectedfor other parts of the body and to be darker thanthe original hair.Infiltration of the dental nervesNerve block of the infraorbital nerve will provideanalgesia of the upper teeth and block of the inferioralveolar nerve will desensitize the lowerteeth. The infraorbital nerve is blocked withinthe infraorbital canal located by palpation betweenthe dorsal border of the zygomatic arch and thecanine tooth. The inferior alveolar nerve is blockedby insertion of a needle through the mental foramenadjacent to the second premolar tooth. Arecent report of chloroprocaine, 1 ml of 2% ateach site, for dental blocks in anesthetized dogsdescribed the onset of analgesia occurring within10 minutes (Gross et al., 1997). The duration ofanalgesia lasted less than 90 minutes in the majorityof dogs but persisted in isolated teeth for up to96 hours. Use of bupivacaine results in a slowonset of action but should provide analgesia postoperatively.Infiltration of the digital nervesThe digital nerves are approached laterally andmedially to the first phalanx of the digit to be renderedanalgesic. A fine needle is introduced subcutaneouslyon each side of the digit (Fig. 15.20) and0.5–1.0 ml of local analgesic solution is injected oneach aspect to block the dorsal and palmar or plantarbranches of the digital nerves. Alternatively,the common dorsal and palmar (or plantar) digitalnerves can be blocked by injections dorsally andventrally at the distal end(s) of the mainmetacarpal (metatarsal) space(s).Intercostal nerve blockThis block is commonly used to provide analgesiaafter thoracotomy and is usually performed by thesurgeon before starting closure of the thoracicwall. The intercostal nerve should be blockedwhere it lies on the caudal surface of the rib.FIG.15.20 Injection of the digital nerves.Injection of 0.25 to 1.00 ml of 0.5% bupivacaine(1mg/kg) should be made as close to the head ofthe rib as possible before the nerve begins to sendoff branches. The block should include two nervesimmediately cranial to the thoracotomy incisionand two nerves caudal. Analgesia may be producedin this way in at least 3 out of 4 dogs andwill persist for the critical first 12 hours after surgery(Pascoe & Dyson, 1993).Interpleural analgesiaInjection of bupivacaine, 1.5–2.5 mg/kg, intothe interpleural space will provide analgesiaafter thoracotomy. The bupivacaine can beinstilled into the pleural cavity at the end of surgerybefore starting wound closure or instilleddown a chest tube, flushed in by several ml of sterilesaline. Analgesia develops most effectivelywhen the dog is in dorsal recumbency so that thebupivacaine collects near the vertebral columnand blocks the nerves at that point. Injection withthe dog in sternal position may only result in ventralanalgesia.Injection of 1.5 mg/kg after lateral thoracotomywas found to produce a significant improvementin PaO 2 and some measures of pulmonary functionfor several hours after anaesthesia when com-

THE DOG 435pared to systemic administration of morphine,1 mg/kg (Stobie et al., 1995) or buprenorphine(Conzemius et al., 1994). Furthermore, analgesiawas at least as good from interpleural bupivacaineas morphine (pain scores were lower after bupivacainefor 10 hours) and better than buprenorphine.A larger dose of bupivacaine willbe needed for analgesia after median sternotomy,however it should be noted that a dose rate of3 mg/kg 0.5% bupivacaine caused hypotensionin some anaesthetized dogs (Kushner et al., 1995).This occurred 15 minutes after injection andwas coincident with peak bupivacaine blood concentrations.Supplemental injections of bupivacaine can bemade down the chest drain tube as analgesiafades. Transient 30 second discomfort may beobserved after injection in the conscious dog.Intra-articular analgesiaPostoperative analgesia after arthrotomy may beprovided by injection of 0.5% bupivacaine(0.5 ml/kg) or preservative-free morphine (0.1mg/kg diluted with saline to 0.5 ml/kg). Aprospective blinded study comparing the analgesiceffects of these drugs after stifle surgery indogs confirmed that less supplemental analgesiawas needed in dogs receiving intra-articular morphineor bupivacaine compared with dogs receivinga placebo (Sammarco et al., 1996). Injectionswere made after the joint capsule was closed,extra-articular stabilization was performed, andsubcutaneous tissues were closed. Intra-articularbupivacaine provided the greatest analgesia withconsistently lower values postoperatively for HR,MAP, respiratory rates, and cumulative painscores (Sammarco et al., 1996). The duration of beneficialeffects of bupivacaine seemed to be up to 24hours.The advantage of local analgesia after joint surgerylies in the provision of analgesia and comfortfor the dog without systemic side effects. Theperipheral antinociceptive effects of opioids aredependent on the presence of inflammation at thesite. The effect of morphine is most likely at a µopioid receptor at the site of injection and mediatedin part by a direct reduction in terminalexcitability (Nagasaka et al., 1996).Intravenous regional analgesiaThis method provides a very safe and simpleway of obtaining analgesia in tractable or sedateddogs of the distal part of the limb for suturing lacerations,excision of tissue masses, and surgery ofthe toes.The dog should be restrained on its side and theappropriate limb held above heart level for 2–3minutes to partially exanguinate it prior to applicationof a tourniquet. Thin rubber tourniquets canbe painful and the least likely to cause the dog distressis a blood pressure cuff inflated to a pressureabove systolic arterial pressure. On the forelimbthe tourniquet is placed either high on the forearmor above the elbow and on the hind limb above thehock. Lignocaine, 4 mg/kg, is injected with a25 gauge needle into any vein distal to the occludingcuff, with the direction of injection being madetowards the toes. The lignocaine should notinclude adrenaline which will cause vasoconstriction,impair diffusion of lignocaine and possiblyresult in tissue ischaemia. Onset of analgesia willbe in about 15 minutes and this will persist as longas the tourniquet is in place. Failure of analgesiawill occur if the tourniquet does not effectivelyocclude arterial or venous blood flow. Sensationwill return to the limb within a few minutes ofremoval of the tourniquet.Intravenous injection may be difficult in thickskinned dogs and this problem can be circumventedby preplacement of a small indwelling catheterprior to exanguination and application of thetourniquet.The dog can be sedated with any drug combinationappropriate for the dog. If the sedatives are tobe reversed at the end of the procedure, it must beremembered that intravenous regional analgesiaconfers no lasting analgesia after the tourniquet isremoved.REFERENCESAlibhai, H.I., Clarke, K.W., Lee, Y.H. and Thompson, J.(1996) Cardiopulmonary effects of combinations ofmedetomidine hydrochloride and atropine sulphatein dogs. Veterinary Record 138, 11–13.Allen, D.A., Schertel, E.R., Muir, W.W. and Valentine,A.K. (1991) Hypertonic saline/dextran resuscitationof dogs with experimentally induced gastric

436 ANAESTHESIA OF THE SPECIESdilatation-volvulus shock. American Journal ofVeterinary Research 52: 92–96.Arnbjerg, J. (1992) Gastric emptying time in the dog andcat. Journal of the American Animal Hospital Association28: 77–81.Atlee, J.L., Bosnjak, Z.J. and Yeager, T.S. (1990) Effectsof diltiazem, verapamil, and inhalation anestheticson electrophysiologic properties affectingre-entrant supraventricular tachycardia inchronically instrumented dogs. Anesthesiology72: 889–901.Baum, V.C. and Palmisano, B.W. (1997) The immatureheart and anesthesia. Anesthesiology 87: 1529–1548.Bernard, J.-M., Doursout, M.-F., Wouters, P., Hartley, C.,Cohen, M., Merin, R.G. and Chelly, J.E. (1991)Effects of enflurane and isoflurane on hepatic andrenal circulations in chronically instrumented dogs.Anesthesiology 74, 298–302.Bonath, K. and Saleh, A. (1985) Long term treatmentin the dog by peridural morphines. 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THE DOG 437Freeman, L.C., Ack, J.A., Fligner, M.A. and Muir III,W.W. (1990) Atrial fibrillation in halothane-andisoflurane-anesthetized dogs. American Journal ofVeterinary Research 51, 174–177.Forsyth, S.F., Guilford, W.G., Haslett, S.J. and Godfrey, J.(1998) Endoscopy of the gastroduodenal mucosa aftercarprofen, meloxicam and ketoprofen administrationin dogs. Journal of Small Animal Practice 39: 421–424.Gelman, S., Fowler, K.C. and Smith, L.R. (1984) Regionalblood flow during isoflurane and halothaneanesthesia. Anesthesia & Analgesia 63, 557–565.Gross, M.E., Pope, E.R., O’Brien, D., Dodam, J.R. andPolkow-Haight, J. (1997) Regional anesthesia of theinfraorbital and inferior alveolar nerves duringnoninvasive tooth pulp stimulation in halothaneanesthetizeddogs. Journal of the American VeterinaryMedical Association 211: 1403–1405.Hall, L.W. (1984) A clinical study of a new intravenousagent in dogs and cats. 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(1990) Ketamine inhypovolemic dogs. Critical Care Medicine 18: 625–629.Hellebrekers, L.J. and Sap, R. (1992) Sufentanilmidazolamanaesthesia in the dog. Journal ofVeterinary Anaesthesia 19: 69–71.Hellebrekers, L.J. and Sap, R. (1997) Medetomidine as apremedicant for ketamine, propofol or fentanylanaesthesia in dogs. Veterinary Record 140: 545–548.Hellebrekers, L.J., vanHerpen, H., Hird, J.F.R.,Rosenhagen, C.U., Sap, R. and Vainio, O. (1998)Clinical efficacy and safety of propofol or ketamineanaesthesia in dogs premedicated withmedetomidine. Veterinary Record 142: 631–634.Hellyer, P., Muir III, W.W., Hubbell, J.A.E. and Sally, J.(1989) Cardiorespiratory effects of the intravenousadministration of tiletamine-zolazepam to dogs.Veterinary Surgery 18: 160–165.Herperger, L. (1998) Postoperative urinary retentionin a dog following morphine with bupivacaineepidural analgesia. 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438 ANAESTHESIA OF THE SPECIESKushner, L.I., Trim, C.M., Madhusudhan, S. and Boyle,C.R. (1995) Evaluation of hemodynamic effects ofinterpleural bupivacaine in dogs. Veterinary Surgery24: 180–187.Kyles, A., Papich, M. and Hardie, E. (1996) Dispositionof transdermally administered fentanyl in dogs.American Journal of Veterinary Research 57: 715–719.Lantz, G.C., Badylak, S.F., Hiles, M.C. and Arkin, T.E.(1992) Treatment of reperfusion injury in dogs withexperimentally induced gastric dilatation-volvulus.American Journal of Veterinary Research 53: 1594–1598.Lascelles, B.D., Butterworth, S.J. and Waterman, A.E.(1994) Postoperative analgesic and sedative effects ofcarprofen and pethidine in dogs. Veterinary Record134(8): 187–191.Lascelles, B.D., Cripps, P.J., Jones, A. and Waterman-Pearson, A. (1998) Efficacy and kinetics of carprofen,administered preoperatively or postoperatively, forthe prevention of pain in dogs undergoingovariohysterectomy. 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THE DOG 439Robinson, E.P., Faggella, A.M., Henry, D.P. and Russell,W.L. (1988) Comparison of histamine release inducedby morphine and oxymorphone administration indogs. American Journal of Veterinary Research 49,1699–1701.Sammarco, J.L., Conzemius, M.G., Perkowski, S.Z.,Weinstein, M.J., Gregor, T.P. and Smith, G.K. (1996)Postoperative analgesia for stifie surgery: acomparison of intra-articular bupivacaine, morphine,or saline. Veterinary Surgery 25: 59–69.Schertel, E.R., Allen, D.A., Muir, W.W., Brourman, J.D.and DeHoff, W.D. (1997) Evaluation of a hypertonicsaline-dextran solution for treatment of dogs withshock induced by gastric dilatation-volvulus. Journalof the American Veterinary Medical Association210: 226–230.Stobie, D., Caywood, D.D., Rozanski, E.A. et al. (1995)Evaluation of pulmonary function and analgesia indogs after intercostal thoracotomy and use ofmorphine administered intramuscularly orintrapleurally and bupivacaine administeredintrapleurally. American Journal of Veterinary Research56: 1098–1109.Takasaki, Y., Naruoka, Y., Shimizu, C., Ochi, G., Nagaro,T. and Arai, T. (1995) Diltiazem potentiates theneuromuscular blockade by vecuronium in humans.Masui 44: 503–507.Tomiyasu, S., Hara, T., Ureshino, H. and Sumikawa, K.(1999) Comparative analysis of systemic and coronaryhemodynamics during sevoflurane- andisoflurane-induced hypotension in dogs. Journal ofCardiovascular Pharmacology 33: 741–747.Torske, K.E., Dyson, D.H. and Pettifer, G. (1998) Endtidal halothane concentration and postoperativeanalgesia requirements in dogs: a comparisonbetween intravenous oxymorphone and epiduralbupivacaine alone and in combination withoxymorphone. Canadian Veterinary Journal39: 361–368.Torske, K.E., Dyson, D.H. and Conlon, P.D. (1999)Cardiovascular effects of epidurally administeredoxymorphone and an oxymorphone-bupivacainecombination in halothane-anesthetized dogs.American Journal of Veterinary Research 60: 194–200.Turnbull, J.M. and Buck, C. (1987) The value ofpreoperative screening investigations in otherwisehealthy individuals. Archives of Internal Medicine147, 1101–1105.Tyner, C.L., Woody, B.J., Reid, J.S. et al. (1997)Multicenter clinical comparison of sedative andanalgesic effects of medetomidine and xylazine indogs. Journal of the American Veterinary MedicalAssociation 211: 1413–1417.Valverde, A., Dyson, D. and McDonell, W. (1989)Epidural morphine reduces halothane MAC in thedog. Canadian Journal of Anaesthesia 36: 629–632.Valverde, A., Dyson, D., Cockshutt, J., McDonell, W.and Valliant, A. (1991) Comparison of thehemodynamic effects of halothane alone andhalothane combined with epidurally administeredmorphine for anesthesia in ventilated dogs. AmericanJournal of Veterinary Research52: 505–509.Vanio, O. (1991) Propofol infusion anaesthesia in dogspre-medicated with medetomidine. Journal ofVeterinary Anaesthesia 18: 35–37.Vesal, N., Cribb, P. and Frketic, M. (1996) Postoperativeanalgesic and cardiopulmonary effects in dogs ofoxymorphone administered epidurally andintramuscularly, and medetomidine administeredepidurally: A comparative clinical study. VeterinarySurgery 25: 361–369.Watkins, S., Hall, L. and Clarke, K. (1987) Propofol as anintravenous anaesthetic agent for dogs. VeterinaryRecord 120: 326–329.

Anaesthesia of the cat 16INTRODUCTIONSo often in the past domestic cats have beenregarded as being simply small dogs, but this attitudehas gradually changed and it is now recognizedthat cats are unique among domesticanimals (Hall & Taylor, 1994). Despite the cat’s reputationfor having nine lives, anaesthetic fatalitiesare not unknown in apparently fit, healthy animals.Indeed, in veterinary general practice in theUK the Association of Veterinary Anaesthetistssurvey in 1990 indicated a death rate of 1 in 550 forfit, healthy cats (Clarke & Hall, 1990). A study ofdeaths associated with the perianaesthetic periodin a University Teaching Hospital (Gaynor et al,1994) estimated the occurrence to be less than 1%,while anaesthetic related complications occurredin approximately 10.5% of cases. It may be thatignorance of the wealth of information relating tofeline physiology and pharmacology appearing injournals and other texts not readily available toveterinary clinicians has contributed to these quiteunacceptably high mortality and morbidity rates.Now that the peculiarities of the species have beenrecognized so that due allowance can be made forthem it is to be hoped that great improvementswill follow.Cats object to being restrained and evenfriendly cats may prove difficult to inject intravenously;unhandled cats may be impossible toanaesthetize using this route. For this reason itmay be necessary to give parenteral drugs by otherroutes, or to induce anaesthesia using inhalationagents. Cats are small in size and this means thatthe margin of error is small; using large syringesand needles can compromise accurate dosage sothat anaesthetic overdoses are easy. For inhalationanaesthesia special apparatus is necessary ifasphyxia is to be avoided. Respiratory obstructioncan occur from even a small blob of mucus in theairway due to the small diameter of the cat’s tracheaand the tendency for laryngeal spasm todevelop. Endotracheal intubation may not reducethis danger, as trauma to the larynx from inexpertintubation may result in obstruction from mucosaloedema postoperatively. Adrenaline releaseduring a stormy induction or recovery can causeventricular fibrillation and this is especially likelyto happen if the heart is suffering from the insultsof hypoxia or hypercapnia due to partial respiratoryobstruction, or to the use of inappropriateanaesthetic apparatus. In the cat, vagal reflexes arevery active during light anaesthesia, they aretriggered by surgery of the head and neck, particularlyof the eyes, nose and larynx, and give riseto laryngeal spasm or, occasionally, to cardiacarrest.Suitable premedication, a quiet inductionof anaesthesia, careful monitoring, the maintenanceof a clear airway, adequate oxygenation,the efficient removal of carbon dioxide, and appropriateattention to fluid and electrolyte balance,should ensure an extremely low mortality rate.441

442 ANAESTHESIA OF THE SPECIESANALGESIAOPIOIDSThe cat usually only vocalizes when pain is acuteand the tone of vocalization is higher than whenthe animal is merely resenting being handled orrestrained. ‘Swearing’ or hissing indicates that theanimal resents interference but purring does notnecessarily mean that all is well. Cats in pain willoften purr when stroked or petted. Chronic pain isoften manifested by the animal hiding in dark cornersof the cage, together with loss of appetite andself-grooming activity. In severe acute pain catsmay pant or mouth breathe.Cats have often been denied adequate analgesiaon the mistaken grounds that the use of opioidscauses maniacal excitement in Felidae. Certainly, theuse of high doses as employed by pharmacologistsstudying pharmacological effects can do so, andviolent excitement may be seen after intravenousinjection of these drugs, as this method of administrationmay expose the brain to a (temporary) overdose.Thus, i.v. administration of potent opioidssuch as fentanyl or alfentanil to conscious cats canonly be recommended if injection is made extremelyslowly. In the correct doses, and by appropriateroutes of administration, opioids will not induceexcitement even in fit, healthy animals (Davis &Donelly, 1968) and if the cat is in pain when theanalgesic is given higher doses are tolerated withoutproblems. Any of the opioids of moderatepotency, which have been recommended for use inother species of animal may be used to provide preorpostoperative analgesia in cats (Table 16.1).TABLE 16.1 Opioid analgesics suitable for use incats;s.c.= subcutaneous injection;i.m.= intramuscular injection;i.v.= intravenousinjectionDrug Dose Route ofadministrationBuprenorphine 0.006–0.010 mg/kg s.c.,i.m.,i.v.Butorphanol 0.2–0.5 mg/kg i.m.Methadone 0.10–0.2 mg/kg s.c.,i.v.Morphine 0.10–0.15 mg/kg s.c.,i.m.,i.v.Pethidine 2–5 mg/kg i.m.(meperidine)Oxymorphone 0.05–0.10 mg/kg i.m.Pethidine and buprenorphineIt is probable that pethidine (meperidine), i.m. attotal doses of 10 to 20 mg to average sized animalshas been the opioid most widely used, but cats insevere pain may safely be given i.m. morphine atdoses of 0.10–0.15 mg/kg. Of the partial agonistdrugs, butorphanol 0.2–0.5 mg/kg i.m. has beenrecommended by Short (1987) and i.m. buprenorphine(0.006 mg/kg) given at the end of surgeryprovides excellent analgesia although at theexpense of considerably delayed recovery fromanaesthesia.NeuroleptanalgesiaNeuroleptanalgesic techniques which employlarge doses of opioid analgesics may cause cats torespond with violent excitement. They are, therefore,contra-indicated in domestic cats and,indeed, in all other Felidae. Low doses of opioidssuch as pethidine (1–2 mg/kg) may be usedtogether with acepromazine but the improvementin sedation over that provided by acepromazine isminimal. However, acepromazine (0.05 mg/kg i.m.) is often used with 0.1 mg/kg morphinei.m. to produce sedation, and oxymorphone,buprenorphine, butorphanol, papaveretum andmethadone can also be used, although doses ofthese opioid drugs need to be kept to a minimum(e.g. butorphanol 0.2–0.4 mg/kg, oxymorphone0.05 mg/kg i.m.). Geriatric or sick cats may be premedicatedwith butorphanol 0.3 mg/kg i.m. andmidazolam 0.1–0.2 mg/kg i.m. prior to facemaskinduction of anaesthesia.NON-STEROIDAL ANTI-INFLAMMATORYDRUGS (NSAIDs)Table 16.2 gives recommended dosages for variousNSAIDs used in cats. Phenylbutazone is quitetoxic to cats, even in moderate doses, but aspirinTABLE 16.2 NSAID dosages in catsDrugDoseAspirin 5mg/kg/ 24 hours orally for < 2daysCarprofen 1–4 mg/kg i.v.or s.c.Ketoprofen 1 mg/kg/24 hours s.c.for

THE CAT 443may be given in small doses by mouth. When indicated10–20 mg of aspirin should be given in divideddoses over a period of 48hours. Given over oneor two days this dose is generally both safe andeffective and allows for the fact that the rate ofhepatic drug metabolism is slow due to a deficiencyof bilirubin-glucuronoside glucuronosyltransferase.Long term aspirin administration canlead to aplastic anaemia or thrombocytopaenia.Carprofen, which does not appear to act byinhibition of cyclo-oxygenase or lipoxygenase, asthe older NSAIDs do, may have fewer side effects.However, experience has shown that all NSAIDsmust be used with caution in cats and only in therecommended doses for periods not in excess of2 to 3days at a time. Other drugs such as acetaminophen(paracetamol), ibuprofen, indomethacin andnaproxen are contraindicated in cats because oftheir hepatoxicity.LOCAL ANALGESIAInfiltration of fracture sites or wounds with localanalgesics can be very effective means of relievingpain in cats, but the total dose of drug administeredmust be carefully regulated. If lignocaine isused the total dose should not exceed 10 mg/kg –this means a maximum of about 8 ml of a 0.5 %solution or 16 ml of a 0.25 % solution in an averagesized, conscious cat. Doses of 0.125 % or 0.070%bupivacaine are correspondingly smaller but theuse of this drug for longer duration analgesia incats has not been widely explored. Gross distensionof the tissues with local analgesic solutionmust be avoided for this interferes with blood flowand may result in delayed wound healing.Epidural blocks are sometimes difficult toproduce and in cats nearly always need to be combinedwith heavy sedation or light general anaesthesiaso their use is limited. If the block is inducedduring preparation of the surgical site it is an effectiveanalgesic long before the end of surgery.Ancillary aids to analgesiaThe importance of good nursing care in alleviatingpain must never be overlooked. Provision ofwarmth and appetizing food should always be apriority. Grooming and wiping around the mouthand eyes with moist cotton wool can do much toincrease the animals’ comfort and they seem to feelmuch better for this attention.SEDATIONPHENOTHIAZINE DERIVATIVESAcepromazineAcepromazine may be given at dose rates of 0.03 to0.10 mg/kg and by the routes described for dogs(p. 394) but in cats the sedation produced is veryvariable and is seldom adequate to assist in controlof an animal. The pharmacokinetics of orallyadministered acepromazine in cats was poorlydocumented until the studies of Verstegen et al.(1994). These workers found the apparent eliminationhalf life to be about 3 hours but the determinationof the elimination constant was hampered byimprecise estimation of the detectable concentrationsusing specific HPLC.Premedication with phenothiazine derivativessuch as acepromazine results in a smoother recoveryfrom anaesthesia and reduces excitement sideeffects of certain anaesthetic agents. Promethazine,a potent antihistamine, is sometimes used beforeSaffan anaesthesia to reduce the risk of allergictypereactions.α 2 ADRENOCEPTOR AGONISTSXylazineXylazine has been widely used, but it may producevariable results. Its action is that of a sedative/hypnoticso that increasing the dose increasesthe depth and duration of sedation produced,and doses of 1 to 3 mg/kg by the i.m. route may beused to give mild to fairly profound sedation; s.c.injection may be used but gives less reliableresults. Vomiting and retching occur as the drugstarts to exert its effect and are most commonlyseen after the lower dose rates are employed.Cardiovascular effects are dose-dependent andalthough there may be an initial period ofhypertension, doses of more than 3 mg/kg resultin cardiac depression and hypotension. Dunkleet al.(1986), using echocardiography, found

444 ANAESTHESIA OF THE SPECIESxylazine to have a marked depressive effect on cardiacperformance and showed that glycopyrrolatemay not completely alleviate the bradycardia dueto this α 2 adrenoceptor agonist. Very high doses ofxylazine have been used to anaesthetize cats butthey are associated with respiratory depression,cardiovascular depression and a very protractedrecovery. They represent overdosage and suchmisuse cannot be condoned.When xylazine is used for premedication,its effects summate with those of all othercentral nervous depressant drugs, so that doses ofall parenterally administered anaesthetics have tobe greatly reduced. This additive effect seemsto depend on the dose of xylazine rather thanthe effect which it has produced, so that greatcare is necessary in even apparently lightlysedated cats. Following xylazine premedicationdoses of barbiturate drugs are at least halved,and doses of Saffan have to be reduced even morethan this. Xylazine has often been used with ketamineand use of these two drugs will be discussedlater.MedetomidineMedetomidine has almost completely replacedxylazine and a dose of 80 µg/kg appears to givesedation similar in type and depth to that producedby 3 mg/kg of i.m. xylazine. Duration ofeffect is dose related, but after an i.m. dose of80 µg/kg clinically useful effects last for approximately1 hour and recovery appears to be completein about 2.5–3.0 hours. Side effects are asexpected for an α 2 adrenoceptor agonist, therebeing marked bradycardia and transient arterialhypertension followed by hypotension, depressionof respiratory rate, pallor of mucous membranesand vomiting early on as sedation develops.Prolonged sedation with high doses of medetomidinemay cause hypothermia.DexmedetomideneDexmedetomidine is the active sterioisomer ofthe racemic medetomidine preparations currentlyavailable for veterinary use. If this pure isomerbecomes available there should be no problemsfor its actions are those of the mixed veterinarypreparation. All that will need to be rememberedis that the effective dose of dexmedetomidine ishalf that of the current commercial preparationof medetomidine employed in veterinarymedicine.Considerations when using α 2adrenoceptor agonistsShould there be any worries about the condition ofan animal sedated with these drugs bradycardiamay be treated with atropine or glycopyrrolate,although this may not be altogether beneficial(Dunkle et al., 1986). Their sedative effects may beantagonized with atipamezole. However, the idealdose of atipamezole is uncertain. Doses of oneto four times the original dose of medetomidinehave been recommended and there is no consensusof the dose to be used to antagonizethe effects of xylazine. High doses, or doses givenat a time when sedation is already waning, haveled to some cats being over-alert. The over-alertstate did not progress to obvious excitement and,when left quiet in a cage, the animals resumednormal behaviour over the course of the next hour.As there are times when it may be desirable for acat to remain very slightly sedated (e.g for thejourney home) the decision as to the most suitabledose for any individual case should be adjustedaccording to the time lapsed since the administrationof the agonist drug and degree of reversalrequired. It should be noted that in the authors’experience under-reversal using lower dosesof atipamezole still leaves the cat liable tohypothermia.BENZODIAZEPINESDiazepamDiazepam and other benzodiazepine drugs produceno obvious sedation when given to domesticcats. They are sometimes used in premedicationfor their muscle-relaxing properties and their useis associated with an increased duration of actionof other drugs used in anaesthesia. Diazepam isgiven in doses of up to 0.5 mg/kg i.m.; its injectionappears to give rise to pain no matter what preparationis used.

THE CAT 445Other benzodiazepinesMidazolam (0.1–0.2 mg/kg) is sometimes usedi.m. mixed in the syringe with ketamine 6 mg/kgto produce a state of good sedation for the performanceof minor procedures such as skin biopsyor radiography.There are currently no reports of the use of climazolamor zolazepam given on their own to cats,but zolazepam is available in Australia, NorthAmerica and on the Continent of Europe in a fixedratio combination with the dissociative agent tiletamine(‘Telazol’, containing 50 mg tiletamine plus50 mg zolazepam per ml) for the induction of astate resembling general anaesthesia. Telazol is notavailable in the UK. Muscle relaxation is poor,there is usually profuse salivation and many catsshow respiratory depression as well as tachyarrhythmias.The author’s experience agrees withthat of Short (1987) that recovery from this combinationcan be prolonged and excited.GENERAL ANAESTHESIAPREANAESTHETIC PREPARATIONPreanaesthetic examination should be carried outin a manner similar to that described in Chapter 1,and any pathological conditions found, togetherwith any pre-existing drug therapy, taken intoaccount during subsequent anaesthesia. In clinicalpractice it is common to find that cats have beenexposed to organophosphorus insecticides fromflea collars or sprays and this may increase theduration of action of suxamethonium given forintubation. Corticosteroids are frequently used incats to control allergies to external parasites andcorticosteroid cover should be given over theanaesthetic and operating periods if the cat hasreceived such therapy in the 2 months precedinganaesthesia.About 12 hours of fasting will usually ensurethat cats have an empty stomach and water needonly be withheld for 2 hours prior to anaesthesia,or the water bowl removed at the time premedicationis given. If surgery is to be carried out on theday of admission, enquiry should be made as towhether the cat was closely confined throughoutthe previous night for a roaming, hunting cat mayhave filled its stomach by eating its prey.ANAESTHETIC TECHNIQUESIntravenous injectionThe minimum of forcible restraint should be usedto enable injection to be carried out. Cats objectstrongly to restraint and respond to its impositionby trying to escape from it, thus inviting moreforcible measures which only too often result inscratched and bitten assistants and a very frightened,excited cat. Such stormy conditions duringinduction of anaesthesia can lead to cats dyingfrom ventricular fibrillation.In conscious cats, i.v. injections are best madeinto the cephalic vein. The animal is placed in a sittingposition on a table of convenient height andfor injection into the right cephalic vein the assistantstands to the cat’s left side, raising and supportingits head between the thumb and fingersof the left hand (Fig. 16.1). In this position theassistant can usually help to keep the cat calmby tickling it below the ears (Fig. 16.2). Theassistant’s right hand is placed so that the middle,third and fourth fingers are behind the olecranon,and the thumb is around the front of the cat’sright forelimb. The limb is extended by pushingon the olecranon and the vein is raised by applyinggentle pressure with the thumb. The limbmust not be held in a vice-like grip becausethis cuts off the arterial blood supply and distressesthe cat.Fig.16.1 Injection into the cephalic vein.Note that onlythe minimum of restraint is being used and as can be seenfrom this cat’s expression it is not frightened or otherwiseupset by the procedure.

446 ANAESTHESIA OF THE SPECIESFIG.16.2 The ‘ear-tickling’ position for restraint duringvenepuncture.This is the position to be used for animalsnot as calm as the one illustrated in Fig.16.1.Most friendly household cats will allow venepunctureto be carried out easily as long as the needleis sharp (and modern disposable ones are) andno thrust is made with the needle. The needle mustbe introduced steadily and gently through the skinand into the lumen of the vein without stabbing.Should it become obvious that more restraint isneeded the assistant can provide this rapidly byholding the cat between his or her body and rightarm while preventing movement from the hindlimbs by pressing the cat firmly on to the table surface.The cat’s head can easily be controlled whenheld firmly in the left hand as described.Sometimes, for the protection of the handler, it isnecessary to wrap the cat in a towel held aroundthe neck, leaving only the head and the limb to beused for injection exposed. If it is clear that greaterrestraint than this is needed, it is probably preferableto abandon attempts at i.v. injection until anappropriate premedication has had time to takeeffect, or to induce anaesthesia by other means.A short needle with a fine bore is suitable forinjections into the cephalic vein and, in general, a25 gauge needle (0.5 mm external diameter),15mm long is ideal as long as venepuncture is freefrom difficulties and the limb is unlikely to bemoved excessively during positioning for operation,but it is probably always preferable to useeither a ‘Butterfly’ set or an over-the-needlecatheter which can be taped securely in position.Introduction of an i.v. needle or catheter may behelped in nervous or ‘needle-shy’ cats by the prioruse of a local analgesic cream (e.g. EMLA, Astra, oramethocaine ointment). The site for venepunctureis shaved and a 2–3 mm thick layer of creamapplied to the skin before covering it with anocclusive dressing for 40 to 45 min. This procedureproduces full thickness skin analgesia and afterremoving the dressing, the skin is wiped clean,disinfected and venepuncture carried out.Although in theory any of the methods ofvenepuncture described for use in dogs may beapplied in cats, the problems of restraint makethem difficult to use in conscious animals. In moribundor anaesthetized animals, the jugular veincan be used. The cat is placed in lateral recumbencywith its neck over a small pad or sandbag,its forelimbs are stretched backwards towards itstail, and the uppermost jugular vein occluded inthe jugular groove near to the sternal inlet by theassistant’s thumb. Jugular venepuncture is particularlyuseful for the administration of intravenousfluid therapy. When relatively large blood samplesare required for diagnostic or other purposes thejugular vein is commonly the only practicable sitefor cannulation, although alternatively, the easilyvisible saphenous medial vein on the medialaspect of the thigh can be used.Endotracheal intubationCats generally maintain a good airway under generalanaesthesia so endotracheal intubation isoften unnecessary for short periods of anaesthesiawhen a mask can be used to administer oxygenand any volatile anaesthetic. The mask may bekept in position by the application of a simple elasticharness passing from hooks on the mask (or awire frame applied over the mask) to around theback of the head (Fig.16.3). However, there aremany instances where intubation is essential andthe cat’s larynx is a small and delicate structure

THE CAT 447FIG.16.3 ‘Hall mask’ secured in position with a simpleharness.easily damaged by rough attempts at intubation.Atraumatic intubation is essential and may bemade difficult by laryngospasm. Endotrachealintubation carried out when there is no strict indicationfor it ensures that the technique can be carriedout quickly when it is essential to do so.Moreover, endotracheal intubation with an appropriatebreathing system can be used to limit atmosphericpollution which might otherwise be seriousduring long operations.LaryngospasmLaryngospasm means the intrinsic muscles of thelarynx contracting to occlude the glottis, preventingventilation and resulting in hypoxaemia. It isvery easily provoked in cats, and when it occurs,atraumatic intubation can only be carried out afterthe laryngeal reflexes responsible for the spasmhave been suppressed by adopting one of the followingmethods:1. The laryngeal mucous membrane of theanaesthetized cat can be desensitized by sprayingit with a solution of a local analgesic drug such as4% lignocaine hydrochloride. The larynx usuallygoes into a spasm when the spray is applied andattempts of intubation should be delayed for about30 seconds or until it is seen to relax. Purelignocaine solutions (2–4 %) should be used sincesome of the additives in medical preparationscause chemical irritation of the mucous membrane(Watson, 1992; Taylor, 1992, 1993) giving rise tooedema-related airway problems after extubation.Relaxation of the jaw muscles is not produced byspraying of the larynx and must be ensured by anadequate depth of anaesthesia. Followingintubation after local analgesic spray it must beremembered that the larynx will be insensitive andthe normal protective reflexes absent until theeffects of the local analgesic have worn off. Theamount of lignocaine used is critical since the drugis readily absorbed from mucous membranes.Care must be taken not to exceed the safe dose(approximately 1–2 mg/kg per laryngeal spray) toavoid systemic effects.In cases where quick intubation is essential thistechnique is not suitable since spraying the larynxwith local analgesic solution does not produceimmediate desensitization and paralysis of thevocal cords. Attempts should not be made to forcea tube through the non-relaxed, active larynx, forthis can cause serious injury. On more than oneoccasion attempts to force a tube through a larynxshowing spasm have resulted in penetration of thepharyngeal wall and passage of the tube down theneck between the oesophagus and trachea, withfatal results.2. When rapid intubation is essential theanaesthetized cat may be paralysed by theadministration of a neuromuscular blocker afterinhaling pure oxygen from a face-mask for 30 to60 seconds to prevent hypoxaemia during thesubsequent intubation procedure. Paralysis is producedmost rapidly by i.v. 3–5 mg of suxamethonium(for an adult cat), and oxygen administrationis continued during the fasciculations caused bythe initial depolarizing action of this agent. Whenrelaxation is complete the cat is intubated throughcompletely flaccid vocal cords (Fig 16.4).Rapid intubation made possible in thisway minimizes the risk of inhalation of regurgitatedstomach contents. Artificial ventilationof the lungs is continued through the endotrachealtube until spontaneous respiration returns

448 ANAESTHESIA OF THE SPECIESVentilation of the lungs using a face-mask is onlyimpossible in cats with upper airway obstruction(usually an abscess or tumour) and in these atracheostomy may be the only way in whichpatency of the airway can be assured so that thewisdom of using suxamethonium in such cases isdebatable. Particular care should be taken to exertonly minimal pressure on the bag in cats withruptured diaphragms, for in them it is very easy toinflate the stomach.Obviously, techniques of introducing an endotrachealtube should be practised when intubationof the cat is not strictly needed so that it can beperformed competently and quickly whenessential.FIG.16.4 Exposure of the larynx by simple lifting of thelaryngoscope blade when the cat is supine.some 3–5 minutes later. Should intubationprove difficult the cat is prevented from becominghypoxic while further efforts are made by manualventilation of the lungs using a face-mask.The mask is applied and the lungs inflated severaltimes with pure oxygen whenever (but preferablybefore) the mucous membranes take on a dusky,cyanotic appearance, and a further attempt ismade to intubate as soon as the colour is a normalpink. Manual ventilation of the lungs through aface-mask is not difficult. Cats’ faces arereasonably uniform in shape and it is easy to get agas-tight seal between a properly designed mask(e.g. modified ‘Hall’ mask) and face, althoughdifficult to achieve with the transparent plasticrubberdiaphragm type of mask. The lower jawmust be pushed forward to ensure the airway isclear and only gentle pressure applied to ventilatethe lungs or gas will be forced down theoesophagus into the stomach. It is possible toventilate the lungs of almost all cats withopen airways with pure oxygen at any timeand well oxygenated cats can be intubatedunder the influence of a neuromuscular blockersuch as suxamethonium without the need forundue haste.3. Laryngeal spasm does not occur during deepanaesthesia but deep anaesthesia cannot berecommended as the depth necessary to preventlaryngospasm is only achieved after considerableoverdose. However, where emergency intubationis required following an accidental overdose ofanaesthetic, it is never necessary to employ eitherof methods 1 or 2 above to secure relaxation of thejaw muscles and vocal cords.Attempts to carry out forcible intubation throughtightly opposed vocal cords, even if initially successful,will result in damage to the mucous membranewith oedema and danger of obstruction afterextubation. The cat’s larynx may also go into aspasm after extubation, especially if there is anymucus on the cords, so endotracheal tubes should,if there are no surgical contraindications, beremoved without any previous deliberate lighteningof anaesthesia and after careful aspiration ofmucus from the airway.Performance of endotracheal intubationIntubation is performed under direct vision assoon as the jaw muscles are relaxed by generalanaesthesia or the effects of the neuromuscularblocker, and intubation is, of course, possible atmuch lighter levels of anaesthesia when neuromuscularblockers are used. Although the expertshould be able to intubate regardless of the positionof the cat, the procedure is best learned if onestandard position is employed until the technique

THE CAT 449is mastered. Two positions are used for teachingintubation; the cat is either prone or supine.In the supine position the head and neck of thecat are extended by placing a small sandbag underthe neck, or by an assistant supporting the headwith a hand placed beneath the neck, and thetongue is pulled out of the mouth, care being takennot to injure it on the teeth. A standard laryngoscopewith an infant-sized blade is introduced andthe tip of the blade placed so that it is over the dorsumof the tongue and resting just in front of theepiglottis. The blade is then lifted to expose theglottic opening and give a good view of the vocalcords (Fig.16.4). The blade is not used as a lever butsimply as a means of lifting the tongue and lowerjaw while the mouth is kept open by use of the littlefinger of the hand which holds the laryngoscopeagainst the upper canine tooth.The endotracheal tube may then be passedbetween the cords without any difficulty. If alaryngoscope is not available, a lighted tonguedepressor can be used in much the same way buttongue depressors are not so easy to control and itmay be found easier to expose the larynx if the catis lying on its side as described for the dog.In the prone position endotracheal intubation isfacilitated by an assistant raising the head andextending the neck. Careful positioning by theassistant ensures that the path for the introductionof the tube is a relatively straight line. Ease of intubationof the cat in the prone position depends onthe assistant being properly trained, whereas inthe supine position the anaesthetist can be in completecontrol of the whole operation.Whatever position is adopted it is importantthat the laryngoscope blade does not come intocontact with the dorsal surface of the epiglottis forthis is likely to be followed by oedema. It is possibleto intubate cats under direct vision but the useof a laryngoscope greatly facilitates the procedureand by displaying the glottic opening enables estimationof the appropriate size of tube to be made.There is often a temptation to use a tube that is toosmall because it is easier introduce, but this shouldbe resisted for a small tube constitutes a partial airwayobstruction. For most adult cats non-cuffedtubes of 4.0 to 5.5 mm internal diameter are suitable;cuffed tubes have to be smaller and the cuffmay cause laryngeal trauma. A tight seal, such asFIG.16.5 New endotracheal tubes must be cut to thecorrect length before use.This is measured from thenostrils to the point of the shoulder.may be needed to prevent inhalation of foreignmaterials, can be ensured by a pharyngeal packof moistened ribbon gauze although relativelysmall, thin walled, cuffed portex tubes are commonlyused for this purpose in North America.Endotracheal tubes should be long enough to passwell beyond the larynx but not so long that theywill enter a main bronchus. The correct length maybe assessed as being from the nostrils to the pointof the shoulder, and all new tubes should be cut tothis measurement before use (Fig. 16.5).An excess of tube between the mouth andanaesthetic breathing system should not be toleratedbecause this, in small animals such as cats,adds significantly to the respiratory deadspace. Atape tied tightly around the tube over the endotrachealtube connector can be secured behind thecat’s ears to anchor the tube in position once it hasbeen introduced (Fig.16.6).PREMEDICATIONAnticholinergic drugs should generally be includedin the premedication given to cats to preventsaliva and bronchial secretions from obstructingthe small-diameter airway; they should be givenwhenever it is proposed to use suxamethoniumfor endotracheal intubation, and to block vagalreflexes. The only contraindications to their use arethe general ones of pre-existing tachycardia orglaucoma. Analgesics should be given whenever it

450 ANAESTHESIA OF THE SPECIESFIG.16.6 A correctly intubated cat with no excesslength of tube protruding from the mouth and the tubesecurely anchored in place with a tape. Apparatusdeadspace is minimal.is necessary to relieve pain, for cats in pain maynot be easy to handle. Sedative use is governed bythe temperament of the cat and by the anaesthetictechnique to follow. Phenothiazines do little tocalm a wild cat, but are useful in quieter animals tocounteract excitement caused by some drugs, andto improve the quality of recovery. Xylazine andmedetomidine markedly reduce the dose of allother agents used for anaesthesia and need to beused with very great care. In the survey of anaestheticproblems promoted by the Association ofVeterinary Anaesthetists of Great Britain andIreland, xylazine was associated with particularlyhigh number of fatalities (1 per 117 cats given thedrug), that were primarily due to overdosage withagents given later to produce anaesthesia.However, xylazine and medetomidine appear tobe useful in reducing the side effects of ketamine,as indeed are the benzodiazepines.Anticholinergic agentsIn the UK atropine, at a total dose of 0.3 mg i.m., i.v.or s.c. for an adult cat and 0.125 or 0.060 mg forsmaller or younger animals, is commonly usedwithout any attempt being made to calculate thedose on a mg/kg basis. This is because atropine isavailable in ampoules which still contain 0.6 mg ofatropine sulphate per ml (a relic of the days whenthe standard dose of atropine for an adult humanpatient in the UK was 1/100th of a grain!).Elsewhere in the world ampoules generally contain0.5 mg of atropine simplifying the calculationof a dose of 0.02 to 0.10 mg/kg. Atropine interfereswith vision and cats which have received this drugshould be handled particularly carefully to avoidinducing panic reactions.Glycopyrronium bromide 0.010 mg/kg i.m. or0.005 mg/kg i.v. may be preferred. It does notcause as marked an increase in heart rate as doesatropine, nor does it cross the blood-brain barrierand so results in less visual disturbance. It may bethe anticholinergic of choice for caesarian sectionor in accident cases which may have a contusedmyocardium.Sedatives and analgesicsPhenothiazines such as acepromazine and propionylpromazineproduce a variable degree of sedation.Some cats become deeply sedated on doses of0.05 mg/kg i.m. of acepromazine, whereas othersshow no appreciable effect. There is a ceiling effectand usually there is no more sedation produced byincreasing doses but they will increase undesirableeffects such as extrapyramidal signs and durationof action. All the phenothiazines directly depressthe temperature regulating mechanisms and catsare prone to develop hypothermia when sedatedwith them. Premedication with acepromazine doesnot significantly reduce the induction dose of propofol(Brearley et al., 1988) but the dose of thiopentalneeded to induce anaesthesia is reduced afteracepromazine premedication by about 30%.Acepromazine is often used in combinationwith opioids to increase sedation without increasingthe side effects of either drug. Most commonly,morphine is the drug used (0.1 mg/kg morphinewith 0.03 mg/kg acepromazine i.m.) but in equivalentdoses other opioids such as papaveretum,butorphanol, methadone and buprenorphine canbe used with acepromazine.Xylazine (0.2–0.4 mg/kg i.m.) and medetomidine(80µg/kg i.m.) may be used prophylacticallywhen there is any likelihood of the presence of afull stomach, for both these drugs induce vomitingin some 60 % of cats. This very property indicatesthat these drugs should be avoided in cats withopen eye or head injuries and those suffering from

THE CAT 451eosophageal or intestinal obstruction. Xylazine(0.55–1.00 mg/kg i.m. or s.c.) may be used prior toketamine administration to counteract the sideeffects of this dissociative agent. It should be notedthat increasing doses of both xylazine and medetomidinecause increased duration of sedation ratherthan increased depth. They also, by slowing thecirculation, delay the onset of action of injectedanaesthetic agents. Medetomidine 15–30 µ/kgsprayed under the tongue is a useful way of sedatingunmanageable cats prior to anaesthesia.The prime role of benzodiazepines in feline premedicationis before ketamine administration tocounteract the rigidity and convulsions producedby this agent, and in animals that may be liable toconvulsions (e.g. epileptics or animals undergoingmyeolography with some of the older contrastagents). They may be considered suitable premedicantsfor cats with cardiorespiratory disease for atnormal doses they have little influence on the respiratoryor cardiovascular systems. Diazepam may begiven i.m. or i.v. at doses of 0.1–0.5 mg/kg i.v. or0.3–1.0mg/kg i.m., and midazolam (0.2mg/kg i.m.)has been used before ketamine (6 mg/kg i.m.).Before propofol anaesthesia the dose of midazolamshould not exceed 0.3 mg/kg i.v.PARENTERALLY ADMINISTEREDANAESTHETICSIntravenous injection is relatively easy in dogs butin cats problems of restraint may make i.v. injectionsmore difficult or even impossible, so thatagents which can be given by other routes (e.g.i.m.) tend to have a greater part to play in felinethan in canine anaesthesia. The disadvantages ofsuch administration – slow induction, variableabsorption, variable effects, prolonged recovery,and inability to dose to effect, – must be weighedagainst the temperament of the cat, skill and experienceof the anaesthetist and the likelihood ofbeing able to carry out a controlled injection. Table16.3 compares the properties of parenteral anaestheticagents commonly used in cats.Thiopental sodiumThiopental may only be given i.v. and in cats itshould be used as a 1.25 % or even more dilutesolution. Induction doses are up to 10 mg/kg andif the cat has not been given sedative premedicationit is probable that the full dose will berequired. Very small doses (e.g. 2 mg/kg) will beneeded after heavy premedication with α 2 adrenoceptoragonists. If thiopental is to be used as thesole agent, incremental doses up to a maximum of20 mg/kg may be used, but at these high doses,saturation of the fat depots may mean that recoverywill take several hours and the effects will stillbe observable the next day. If recovery is prolonged,the cat must be kept warm, for the developmentof hypothermia (more marked whenacepromazine premedication is used) will delayrecovery still more.Methohexital sodiumMethohexital may be given only i.v., and is used ata concentration of 0.5% for feline anaesthesia.TABLE 16.3 Injectable anaesthetics in the cat. Dose rates,duration of action and recovery times mustbe regarded as only approximate and the use of other agents concurrently can prolong or reduce thesedoses and times.Moderate or heavy preanaesthetic sedation will decrease these doses and prolong thetimes for anaestheia and recoveryAgent Dose rate (mg/kg) Route Approx.duration of Approx.time toanaesthesia (min) standing /walking (h)Ketamine 10–35 i.m. 30–45 3–4Ketamine 2–10 i.v. 20–40 1–4Methohexital 5–12 i.v. 5–10 1.0–1.5Pentobarbital 20–30 i.v. 60–90 4–8Propofol 5–8 i.v. 3–6 0.5Saffan 4–12 i.v. 5–15 0.75–2.00Saffan Up to 18 i.m. 5–20 Average 1.0Thiopental 15–25 i.v. 5–15 1–2

452 ANAESTHESIA OF THE SPECIESAlthough it can be used for induction of anaesthesiaat a dose of about 5 mg/kg, and givenin incremental doses to maintain anaesthesia,in cats its tendency for causing excitementmeans that recovery is often far from uneventful.The use of sedative premedication helps to reducethe incidence of excitatory phenomena but ingeneral, is only employed in cats when veryrapid recovery is needed (e.g. after caesariansection).Pentobarbital sodiumUntil some 30 years ago pentobarbital was widelyused in general practice and experimental laboratoriesas an anaesthetic for cats. Doses of 25mg/kgi.v., half given fast to avoid induction excitementand the rest given slowly over 2–3 minutes toeffect, give about 2 hours of surgical anaesthesia.Recovery from such doses is very prolonged, thecat not becoming fully conscious until the nextday. Despite the long-acting nature of the drug andthe respiratory depression it causes, pentobarbitalanaesthesia has, over the years, been successfullyand safely administered clinically to many thousandsof cats. Most deaths following pentobarbitalanaesthesia probably result from hypothermia andit is essential that cats are kept warm in the recoveryperiod.Pentobarbital can also be given by intraperitonealinjection but the results are variable,depending on its absorption from the peritonealcavity. Induction of anaesthesia is slow andcats frequently show a stage of marked excitementso that if released from a cage at this stagethey may literally run around the walls of theroom. Today, this route of pentobarbital administrationshould, if used at all, be restricted tothose laboratory workers untrained in moreacceptable anaesthetic methods. Some veterinarianshave in the past administered pentobarbitalto cats by intrapleural injection andalthough absorption from this cavity is betterthan from the peritoneum, injection is very painfuland the potential complications are such that theintrapleural route must be regarded as quite unacceptable.Today there is little to recommend theuse of pentobarbital even i.v. in veterinary clinicalpractice.Alphaxalone-alphadolone (‘Saffan’)Since its introduction into clinical feline anaesthesiathis steroid mixture has become an extremelypopular anaesthetic agent, especially in generalpractice in the UK. Doses are commonly expressedas mg/kg of the total 12 mg/ml steroid content ofthe solution. This solution is non-irritant and isgiven to cats i.v. or i.m. Doses of 3 mg/kg i.v. produceunconsciousness for a few minutes, whilstdoses of 9 mg/kg give 10–15 minutes of anaesthesiawith very little increase in the initial depth ofunconsciousness or respiratory depression. Theincreased duration of action with initial higherdoses reaches a plateau at about 18 mg/kg i.v. andgiving higher i.v. doses is pointless and may bedangerous. If it is necessary to prolong anaesthesiafurther increments may be given later on, or aninhalation agent employed.Both steroids are rapidly broken down in theliver so that an incremental dose regimen does notresult in undue delay in recovery and cats are usuallycompletely conscious within 2hours of administrationof the last increment. The rapid breakdownof the steroids is undoubtedly responsible for thewide safety margin as far as dose is concerned.Induction of anaesthesia is usually smooth andrapid, but occasionally it is complicated by retching,vomiting and laryngeal spasm. Although inthe majority of healthy, unpremedicated cats thei.v. dose needed to produce some 15 minutes ofanaesthesia (9 mg/kg) may be given as a singleinjection, in a few it may be an overdose. It certainlycauses a significant depression of cardiacoutput, stroke volume and peripheral vascularresistance (Dyson et al., 1987).The authors much prefer to give an initial i.v.injection of 2 to 3 mg/kg and administer the rest ofthe dose after gauging the response to the initialinjection. Where sedative premedication is giventhe dose of Saffan has to be reduced and if xylazineis employed a reduction of more than 50% may benecessary. The use of other i.v. agents with Saffanmay result in severe respiratory and cardiovasculardepression and the manufacturers state thatSaffan should not at any time be combined withany other i.v. anaesthetic.There is normally little respiratory depressionduring Saffan anaesthesia although high doses i.v.

THE CAT 453(more than 12 mg/kg) may give rise to somedepression and a period of apnoea. Hypothermiamay occur but is rarely clinically significant unlessthe operation involves wide opening of the bodycavities for more than 15 minutes, or the cat is fluiddepleted. Recovery from Saffan anaesthesia isoften rather restless and if the animal is stimulatedin some way recovery may be violent, the catbecoming rigid, twitching, convulsing and evenshowing opisthotonus. The smoothness of recoverycan be improved by ensuring that the animal ispain-free and left undisturbed in a quiet, warm,comfortable cage. Acepromazine premedication isalso claimed by many to improve the quality ofrecovery from Saffan anaesthesia.When Saffan is used as an induction agentbefore inhalation anaesthesia it is often necessaryto increase the concentration of any volatile agentto above what might be expected in order tosuppress the twitching associated with recoveryfrom Saffan. Laryngeal spasm may be provokedby head and neck surgery under light Saffananaesthesia (reports to the Association ofVeterinary Anaesthetists) and for this type of surgerycats must be premedicated with atropine andintubated.Saffan may also be given i.m. and doses of18 mg/kg are followed in about 10 minutes byanaesthesia which lasts some 10 to 20 minutes.These doses represent a rather large volume (4.5ml for a 3 kg cat) but the injection appears painlessand cats do not resent administration. Lowerdoses can be used for minor procedures such asdematting the coat. As the anaesthetic is eliminatedso rapidly from the body, it is ineffective ifgiven either s.c. or into the fascial planes betweenmuscles so to ensure its proper effect it should begiven deep into the vastus group of muscles. Ani.m. administration is never as reliable as i.v. and itis, therefore, generally employed either wheredeep sedation rather than anaesthesia is needed orwhere it is possible to supplement by an i.v. injectiononce the cat is unconscious.Hyperaemia and swollen paws, ears and nosesare common following Saffan and there are reportsof laryngeal and pulmonary oedema. Other sideeffects include sneezing, retching, vomiting andlaryngeal spasm, but provided a clear airway ismaintained and respiration and cardiac functionare not depressed by other agents, Saffan isundoubtedly a reasonably safe induction andmaintenance agent for use in general practice.Evans estimated from the quantities sold by themanufacturers coupled with the deaths reportedto them, that the mortality rate was less than 1 in10 000, but it seems more likely that the true mortalityrate for Saffan in cats is nearly 10 timesgreater than this at about 1 in 900 (Clarke & Hall,1990).PropofolPropofol has been used quite extensively in cats asan i.v. anaesthetic. The dose needed to induceanaesthesia is 6 to 7 mg/kg in both unpremedicatedanimals and in animals premedicated with0.03 mg/kg acepromazine. The dose followingmedetomidine premedication has yet to be establishedbut is likely to be very low. Induction issmooth and blood pressure and heart rate are wellmaintained, but there is some significant respiratorydepression. Maintenance of anaesthesia withpropofol requires about 0.4 mg/kg per min by continuousinfusion but may be less when intermittentdoses are administered as needed to simplyobtund responses to particularly painful stimuli.Recovery is generally smooth but retching, sneezingor pawing of the face may occur in about 15%of cases.The cat’s liver does not metabolize phenols asrapidly as does the dog’s liver and although considerablefirst pass extraction of propofol is said tooccur in the cat’s lungs (Matot et al., 1993), rapidrecovery is not a marked feature of propofol anaesthesia.Also, some cats have disturbed recoveries,pawing at their noses in a manner reminiscent ofthat seen after the use of Saffan. Acepromazinepremedication appears to improve the quality ofrecovery. Propofol seems less likely than Saffan toproduce anaphylactoid reactions but, in the vastmajority of cats these reactions with Saffan are relativelymild, so this is not a reason to prefer theuse of propofol. It is doubtful whether propofoloffers any major advantage over other i.v. agentsand, indeed, many cats have very prolongedrecoveries, while the mortality rate, although notyet reliably established, may prove to be quiteunacceptable.

454 ANAESTHESIA OF THE SPECIESKetamineKetamine is available as the water soluble racemicmixture of two isomers and the standard forveterinary use is a solution containing 100 mg/mlketamine hydrochloride with benzethonium chloride0.01% as preservative. Lower strength solutions(10 mg/ml and 50 mg/ml) are available for usein man. As well as by i.v. injection ketamine canbe administered i.m. or s.c. and this has encouragedits use in cats that are difficult or impossibleto handle. The volume of solution which has to beinjected is small and the i.m. or s.c. injection can,when deemed to be essential, be made by a dartprojectile fired from a blowpipe. It should benoted, however that i.m. or s.c. injection of ketamineappears to be painful, in that it is often violentlyresented by the animal. Application to themucous membranes of the mouth (squirting froma syringe) can also be an effective route of administrationin cats which are difficult to handle. Whengiven i.v. there is usually a delay of 1–2 minutesbefore its effects become apparent, but this is thebest route of administration. Ketamine has becomea drug of abuse in man and care must be taken inits safe storage and disposal. In the USA it is now ascheduled drug.Cats become recumbent 3–5 minutes followingeither 10 mg/kg or 20 mg/kg i.m. Sternal recumbencyis usually regained 30 minutes after thelower dose and 50 minutes following the higherone, but standing and behaving normally takesconsiderably longer. Higher doses are seldommore reliable and result in very long recoveryperiods associated with ataxia, increased motoractivity and increased sensitivity to external stimuli.In man, ketamine emergence reactions are coupledwith a range of hallucinations and moodalterations but, of course, it is impossible to establishwhether similar phenomena occur in cats.The manufacturers recommend i.m. doses 11–33 mg/kg, the lower doses to be used for minorrestraint, and the larger doses for minor surgeryand restraint of fractious cats. Very small kittens ofless than 4 weeks of age appear to need still higherdoses of up to 35 mg/kg. Doses of up to the lowerend of the range are recommended when the drugis given i.v. Today, however, for the reasons givenbelow, ketamine is seldom used on its own andthese doses are greatly excessive when many of thecurrent drug combinations are employed.Ketamine induces a state of catalepsy withsome degree of analgesia. It appears to abolishresponses to superficial, painful stimuli, but not toabdominal pain (Sawyer et al., 1991). Ketaminedosed cats exhibit marked muscle tone, their eyesremain open and spontaneous movement quiteunrelated to any stimulation may occur. Suchmovements may lead an anaesthetist unaccustomedto the effects of the drug to assume thatanaesthesia is lightening, but this is not the caseand further doses given in attempts to suppressthem result in overdosage. Laryngeal and pharyngealreflexes are often said to be retained, but noreliance can be placed on this protection and allnormal precautions to protect the airway must betaken. Salivation is often profuse, so atropine orglycopyrrolate premedication is advisable.Although ketamine is claimed to produce minimalrespiratory depression, relative or absolute overdosescause apnoea (Clarke & Hall, 1990). It isessential that cats should be kept under continuousobservation from the time ketamine is givenuntil it is obvious that recovery is complete.Ketamine produces sympathomimetic effectsbut has a negative inotropic on the myocardium sothat the overall effect on the circulatory systemmay vary according to the clinical state of the animal.In healthy, normovolaemic cats the stimulatoryaction appears to predominate and the ABPand heart rate increase. The drug normally causessome depression of respiratory function but incats these effects are complex and dose-dependent.When ketamine is used in healthy individuals thedegree of respiratory depression is usuallyinsignificant.Ketamine combinationsA wide range of sedative agents have been used inorder to reduce side effects, in particular those ofemergence excitement and increased muscle tone.Where premedication enables a reduction in thedose of ketamine, speed of recovery may beenhanced. Atropine is generally recommended atdoses of 0.03 to 0.05 mg/kg to reduce salivation.Inhalation anaesthesia may be used after ketamineinjection and may be maintained by suitable

THE CAT 455combinations of O 2 with N 2 O or halothane, orisoflurane.AcepromazineAcepromazine (0.01–0.03 mg/kg i.m.), althoughwidely used, has little influence on the dose of ketaminesubsequently required. It reduces the musclerigidity associated with ketamine alone andappears to produce a state resembling more conventionalgeneral anaesthesia, although the eyesremain open with a dilated pupil. Better conditionsresult when butorphanol (0.4 mg/kg i.m.) isadded to increase analgesia (Tranquilli et al., 1988).Diazepam and midazolamDiazepam (1 mg/kg) is also disappointing butmidazolam with ketamine (0.2 mg/kg midazolamwith 10 mg/kg ketamine) mixed in the samesyringe and administered i.m. produces heavysedation with good muscle relaxation (Chambers& Dobson, 1989) suitable for radiotherapy or radiography.Useful sedation lasts about 30 minutes(some cats become cyanosed when breathing air)and recovery is usually complete within 2–3 hours.XylazineXylazine has been used for some years to preventketamine-induced emergence excitement but itsuse is also associated with the side effects of bradycardia(unless anticholinergics have been used forpremedication) and vomiting. Earlier high doseshave been replaced by much safer ones and therecommendation now is that 1 mg/kg of i.m.xylazine is followed by 5 mg/kg of i.m. ketamine.This yields a reasonably rapid recovery. The doseof i.m. xylazine has been reduced to 0.5 mg/kg andthe i.m. dose of ketamine increased to 20–25mg/kgby Arnbjerg (1979) with a recorded death rate of3 in over 7000 cats. Thus even these dosage ratesare comparatively safe but the prolonged recoveryperiod of 3–5 hours may present problems in busypractice conditions.MedetomidineThe relatively recently introduced α 2 adrenoceptoragonist, medetomidine, provides more analgesiathan does xylazine and hence the dose of ketamineneeded to produce surgical anaesthesia can bereduced to 5–7 mg/kg i.m. when preceded by80µg/kg i.m. medetomidine. These doses producea mild bradycardia and no apnoeic periods butincreasing the ketamine dose to 10 mg/kg resultsin tachycardia (? from hypotension) and briefperiods of apnoea. The data sheet for ketaminesuggests a dose of 80 µg/kg i.m. medetomidine followedby a 2.5–7.5 mg i.m. ketamine and that thesemay be combined in the same syringe, althoughthe vials should have separate needles inserted forwithdrawal to minimize the likelihood of crosscontamination. Accurate measurement of the doseis best assured by the use of a tuberculin syringe.Surgical anaesthesia of 30 to 60 minutes durationfollows after an interval of some 3–4 minutes.Except for heart and respiratory rate records,published data concerning the cardiovascular andrespiratory effects of these drug combinations islacking. In view of the similar actions of xylazineand medetomidine it seems reasonable to assumethat medetomidine/ketamine combinations willcause some degree of arterial hypotension. Thecardiovascular depressant effects of medetomidine/ ketamine combinations can be countered bythe administration of 200 µg/kg i.m. atipamezole(Verstegen et al., 1991a). In clinical practice it isunwise to administer atipamezole until the effectsof ketamine have waned – probably about onehour after a dose of 5 mg/kg – because of the likelihoodof ketamine emergence excitement.TiletamineTiletamine, a dissociative agent related to ketamineis seldom if ever used as the sole sedative orimmobilizing agent in cats. Investigations byTABLE 16.4 Composition of Zoletil (marketed byVirbac) according to the direction sheetOne vial contains: Zoletil Zoletil Zoletil20 50 100Tiletamine 50 mg 125 mg 250 mgZolazepam 50 mg 125 mg 250 mgDissolved in 5 ml 20 mg/ml 50 mg/ml 100mg/mlwater,each mlcontains

456 ANAESTHESIA OF THE SPECIESGarmer (1969) showed that i.m. it was painful, highdoses were required to abolish response to stimulationand recovery was prolonged and excited.Recently it has been combined with zolazepam, amember of the benzodiazepine group of drugs, as‘Telazol’ or, in Australia, ‘Zoletil’ (Table 16.4).Injection produces profuse salivation that canbe controlled by atropine, the degree of musclerelaxation is poor in comparison to medetomidine/ketamineand ketamine/xylazine and respiratorydepression is equal to that produced bytiletamine alone (Verstegen et al., 1991b). Recoverytakes 2–6 hours and if the cat is stimulated in anyway there may be periods of excitement. If morethan the one initial dose has been administeredrecovery can be very prolonged.INHALATION ANAESTHESIAInhalation agents may be used in cats to induceand maintain anaesthesia but because of the smallsize of the animals it is relatively easy to administeran overdose of volatile agents. The fit, unsedatedcat strongly resents attempts to force it tobreathe volatile agents from a face-mask and it isseldom possible to avoid struggling or fightingwith the animal at some time during attempts toinduce anaesthesia in this way. For this reasonmany anaesthetists prefer to induce inhalationanaesthesia by placing the cat in a rectangularglass or clear plastic chamber and piping the gasesand vapours into the chamber (Fig. 16.7). Scavengingis recommended to avoid pollution of the roomair. The cat usually accepts this quite calmly providedit can see out of the container and the transparentwalls of the chamber enable the behaviourof the cat to be observed. It must be removed fromthe chamber as soon as it loses consciousness andcollapses in a state of light anaesthesia.Restraining a fully conscious, unsedated catand applying a face-mask to force it to inhale anyanaesthetic mixture, although often done in thepast with apparent safety, must be regarded asbeing inhumane. It results in adrenaline release,which in the frightened animal may occasionallyresult in ventricular fibrillation and death, but themethod has been applied without fatalities forvery many years. The animal is usually restrainedin lateral recumbency with all four legs held by anassistant while the anaesthetist controls the headwith one hand and uses the other to apply the facemask.Cats seldom object to breathing a nitrousoxide/oxygen mixture and the volatile agents maybe added in gradually increasing concentrations.The normal rule is to increase the concentration ofthe volatile agent every three breaths until the safemaximum is obtained. This technique avoids theprolonged breath-holding which occurs if the animalis suddenly introduced to high induction concentrationsof the anaesthetic. If the cat struggles itusually breathes rapidly and deeply so the inductionof anaesthesia is more rapid; if breath-holdingis encountered care must be taken not to releasethe restraint as the cat may be in the stage of narcoticexcitement. In heavily premedicated or verysick cats, induction of anaesthesia by volatileagents (e.g. 2.5 % for halothane or 3.5 % for isoflurane)given by face-mask can usually be carriedout without provoking excitement or strugglingand is often the method of choice.Breathing circuitsFIG.16.7 A cat box with transparent sides for theinduction of inhalation anaesthesia.Scavenging of gasesissuing from the box is to be recommended.Any breathing system used to administer inhalationanaesthetics to cats must have a very lowresistance and small deadspace. In practice, thislimits the possible systems to non-rebreathingones because the soda lime canister and connect-

THE CAT 457TABLE 16.5 Average cardiovascular data foranaesthetized normal adult cats of all domesticbreeds (measurements made at the CambridgeSchool between 1952 and 1990)Respiratory rate 24–28 breaths/minTidal volume 12–24 mlMinute volume 280–760 ml/minHeart rate 160 beats/minArterial bloodpressure:systolic120–140 mmHgdiastolic70–80 mmHgArterial blood pH 7.34PaO 29/(95) 5 mmHg (12–13.9 kPa)PaO 235 mmHg (4.7 kPa)ing tubes of rebreathing systems create too muchresistance to respiration.The Ayre’s T-piece systemThis is the circuit of choice when the cat is intubatedbut it may also be used with a face-mask. It hasminimal resistance and deadspace and IPPV canbe carried out very efficiently by squeezing thepartially filled bag of the Jackson-Rees modificationof the T-piece system. Fresh gas flows of twicethe minute volume of respiration (Table 16.5) aresufficient to prevent rebreathing.Co-axial systemsIn practice the Bain system does not behave like aT-piece system and appears to offer too muchresistance for spontaneously breathing cats, but itseems that the performance of the modified Bainsystem is improved if the ‘tail’ of the bag is amputated!The Lack system behaves rather like aMagill system but the weight of the tubing tends todrag the face-mask away from the face or endotrachealtube out of the trachea. The expiratory valveneeds to be removed from the Lack circuit. Theparallel circuits in these configurations offer noadvantage in feline anaesthesia.The Magill systemAlthough the expiratory valve of the Magill systemcreates too much resistance for cats, the systemis frequently used with a face-mask toadminister inhalation anaesthetics. If the mask isapplied tightly to the cat’s face most anaesthetistslift the valve plate by introducing a needle or pinbeneath the plate. Other anaesthetists use a largeface-mask which is not applied tightly to the cat’sface so that expiration can take place freely betweenthe face and mask. These modifications of the systemcan result in considerable pollution of theatmosphere of the room by the anaesthetic agents.In the USA circle systems with their paediatrichoses designed for use in small human infants arecommonly used with a fresh gas inflow of 1 l/minfor cats weighing more than 3 kg. Circuitsdesigned for adult human patients can be satisfactorilyused in cats, but gentle IPPV is essential.Inhalation agents usedAll the inhalation anaesthetics may be used in catsin a similar way to that in which they are used indogs (Chapter 15). Chloroform has no place todayin feline anaesthesia.Nitrous oxideNitrous oxide/oxygen mixtures (3/2 in the Ayre’sT-piece and 50/50 in circle rebreathing systems)are useful after anaesthesia has been induced withSaffan, especially when it has been given i.m., asthey seem to suppress the muscle twitching oftenseen when the effects of Saffan are waning.However, nitrous oxide/oxygen mixtures are usuallyused in feline anaesthesia simply as a vehiclefor the delivery of volatile agents.EtherFor well over 100 years ether was used as a particularlysafe anaesthetic for cats. Today, however,because of its inflammable nature it is largely discardedin most developed countries in favourof more recently introduced non-inflammableagents. Nevertheless, although induction is slower,the margin for error is much greater than it is formore potent agents such as halothane and isoflurane.Many thousands of cats have been anaesthetizedwith ether and the number of deathswhich can be attributed to its proper use is small. Itappears that anaesthetization is often followed by

458 ANAESTHESIA OF THE SPECIESnausea for many cats are reluctant to eat for thefirst 24–48 hours after ether anaesthesia. This is,perhaps, a small price to pay for safety and theonly real objection to the use of ether in felineanaesthesia is the risk of fires or explosions when itis mixed with air or oxygen. Anticholinergics areessential to reduce the copious secretions inducedby the irritant nature of its vapour.HalothaneCardiac arrhythmias occur quite frequently in catsunder halothane anaesthesia. When they occurthey can usually be abolished and normal rhythmrestored by the performance of IPPV to increasethe gaseous exchange in the lungs. It appears thatthe respiratory depressant activity of halothaneallows CO 2 to accumulate in the body and once thePaCO 2 exceeds a certain threshold value arrhythmiasappear. Lowering the PaCO 2 by IPPV is followedby a prompt return to normal cardiacrhythm. Very satisfactory anaesthesia results whenan accurately calibrated vaporizer is used andhalothane is administered in oxygen or a nitrousoxide/oxygen mixture through a non-rebreathingsystem. For cats, the total fresh gas flow to a T-piece system need not exceed 1.5 to 2.0 l/min, littlehalothane is used and consequently, the method isnot expensive. Provided ducting of waste gasesfrom the open end of the T-piece is practised, thereis no justification for attempting to use closedmethods of administrationMethoxyfluraneIn cats methoxyflurane has been used to reinforcethe effects of nitrous oxide/oxygen mixtures butthis agent is no longer generally available for veterinaryuse.EnfluraneAlthough as yet there is little published informationrelating to the use of enflurane in cats it hasbeen used quite successfully to produce anaesthesiawith short induction and recovery periods.It may be volatilized, preferably from any calibratedvaporizer in a stream of oxygen or nitrousoxide/oxygen and delivered to the cat by any ofthe methods usually employed in feline anaesthesia.Evidence of seizures from central nervous irritationhas not been observed, but myotonia iscommon during recovery from anaesthesia.IsofluraneIsoflurane is a quite satisfactory agent for felineanaesthesia although in cats not subjected tosurgical or other stimuli it produces marked dosedependentrespiratory depression. Dose-dependentarterial hypotension is of the same order as thatproduced by halothane but results from reductionin peripheral resistance rather than the cardiacdepression associated with halothane. Unlike itsisomer, enflurane, it has not been linked to cerebralirritation in cats.SevofluraneThere seems to be nothing exceptional in relationto the use of sevoflurane in cats. With the possibleexception of a higher heart rate with sevoflurane,its respiratory and circulatory effects are similar tothose of isoflurane and halothane (Hikasa et al.,1996).DesfluraneThe cardiopulmonary effects of desflurane in catsduring spontaneous and controlled ventilationwere recorded by McMurphy and Hodgson (1994)who in 1995 reported the MAC to be 9.79 ± 0.70vol%. They noted that 1.7 MAC of desfluranecaused a profound depression of respiration whichthey suggested resulted in high pulmonary arterypressures. Desflurane apparently had a sparingeffect on cardiac output similar to isoflurane.Because a newly designed, special temperaturecontrolled,pressurized vaporizer is needed to deliverthe agent in a predictable fashion, this with theassociated costs makes it likely that the developmentof desflurane anaesthesia in cats will be slow.Intermittent positive-pressure ventilation(IPPV)In the intubated cat, IPPV can be carried out bymanual compression of the reservoir bag of the

THE CAT 459Jackson-Rees modification of the T-piece system. Itis possible to apply IPPV when an uncuffed endotrachealtube is in place and indeed the absence ofa cuff acts as a safety device by preventing theapplication of too high a pressure and over-inflationof the small feline lungs. When the cat is notintubated, IPPV can be applied through a tightlyfitting face-mask attached to either an Ayre’s T-piece or Magill system, but care must be taken toensure that the airway is clear and that too muchpressure is not applied or the stomach will beinflated. A clear airway is produced by avoidingover-flexion or extension of the head and applyingforward pressure behind the vertical ramus of themandible as the face is pushed into the mask. TheMagill system is only used for emergenciesbecause when IPPV is performed it gives rise toalmost total rebreathing so that the mask must beremoved from the patient’s face every few breathsto allow exhalation to the atmosphere and themask to refill with fresh gas.Most mechanical ventilators used in canine surgeryproduce tidal volumes which are too large forcats and if they are used in these animals a controlledleak has to be introduced into the circuit.Ventilators such as the Drager, the Halliwell andthe Columbus are quite suitable for use in felineanaesthesia but they are needed too infrequentlyto justify their purchase unless their routine use isnecessary.Neuromuscular blocking agentsIn cats there is seldom any indication for the use ofcompetitive neuromuscular blocking agents asmuscle tone is insufficient to interfere with mostfeline surgery. However, when they are indicated(e.g. for intraocular surgery) they may be used atthe same dose rates, and their action antagonizedin the same way, as described for the dog. Thedepolarizing agent, suxamethonium, is used to aidendotracheal intubation or endoscopy and in catstotal doses of 3–5 mg i.v. will, after the initial musclefasciculation, give complete relaxation forsome 4 – 6 minutes. During the period of apnoeaIPPV is, of course, necessary, and no difficulty isexperienced in continuing this IPPV for muchlonger than the paralysis due to the neuromuscularblocker lasts.Special problems in feline anaesthesiaThe small size of neonatal kittens renders themparticularly prone to develop hypothermia andrespiratory obstruction. Kittens should alwaysbe premedicated with an anticholinergic (0.005 mgof atropine is appropriate) and anaesthesia isbest induced and maintained with volatile anaesthetics.Endotracheal intubation should be avoidedunless absolutely essential – as it is if IPPV is needed.Very careful attention should be given to the maintenanceof body temperature and to the replacementof blood or fluid losses.POSTOPERATIVE CAREEndotracheal tubes should be removed from catswhen anaesthesia is still reasonably deep as theirremoval during light anaesthesia can give rise totroublesome laryngeal spasm. The quality ofrecovery in cats depends to a great extent on theanaesthetic agents that have been employed. It isusually smooth and uneventful after inhalationanaesthesia but cats may be hypersensitive tonoise and other stimulation after Saffan or ketamine.Whatever anaesthetic agents have beenused, recovery will be improved by keeping the catin a quiet environment. It is particularly importantfor the cage to be of adequate size, as many of the‘seizures’ seen during recovery are provoked bythe cat being unable to stretch out fully withouttouching the sides of the cage. Cats are prone todevelop hypothermia and the recovery areashould be kept warm or the cage should be heated.It is difficult to keep cats warm with heated waterpads or hot water bottles because their claws causepunctures if the animal moves vigorously as itregains consciousness.Adequate pain relief is as essential in cats as inall other animals. Narcotic analgesics may begiven i.m. as long as excessive doses are notemployed. Morphine in doses of 0.1 mg/kg doesnot cause excitement even in fit, healthy cats, andpost trauma it gives postoperative pain relief for 3to 4 hours. Pethidine, given at a dose of 4 mg/kggives analgesia for 2hours but no effect is apparentafter 4 hours and the use of this agent should probablybe restricted to preoperative use. In the

460 ANAESTHESIA OF THE SPECIESauthors’ experience doses of 10 to 25 mg (dependingon the size of the cat) given i.m. at 3 – 4 hourlyintervals produce excellent pain relief in the postoperativeperiod for the majority of animals.Buprenorphine (0.006 mg/kg i.m.) can also be veryeffective.As cats start to regain consciousness they mayreact to the presence of such things as chest drainsand occasionally it is necessary to give drugs tocontrol the animal at this time, even if they delayreturn to full consciousness. In such circumstances,provided that barbiturates have not beenemployed during anaesthesia, small incrementaldoses of i.v. Saffan given into an intravenousinfusion by the nursing staff as required toproduce the necessary control, may be prescribedquite safely and the cat still awakens rapidly afterthe last dose.It is often claimed that if local analgesics havebeen sprayed on the laryngeal mucous membranesto permit endotracheal intubation, thecat should not be allowed access to food orwater for 4 hours afterwards in case laryngeal protectivereflexes are still blocked. In practice,the local analgesic is absorbed so rapidly fromthe laryngeal mucous membrane that it becomesineffective about 15 minutes after application.Cats may always be encouraged to eat anddrink, provided that there are no surgical contraindications,as soon as they have fully regainedconsciousness.LOCAL ANALGESIALocal analgesia is seldom used in cats because ofthe problems involved in adequate restraint and inrestricting the dose of drug to non-toxic levels inthese small, active animals. However, it can bevaluable in very sick or moribund cats or when theanimal is controlled by deep sedation or lightanaesthesia. Whatever method of local analgesia isemployed care must be taken that the total dose ofthe agent does not constitute a toxic dose of about0.12 g, i.e. 12 ml of 1% lignocaine, or its equivalent,in an 4 kg adult cat. In cats local analgesia usuallyinvolves local infiltration of the operation site, buttechniques such as IVRA or specific nerve blockscan be employed if restraint is adequate.Epidural analgesiaThe technique is identical to that used in dogsand using 2% lignocaine doses of 1 ml/ 4.5 kgadministered at the lumbosacral space will blockcranially to the level of L1, while doses of 1ml/3.4kg extend the block to the fifth thoracic vertebrallevel.Most practical anaesthetists consider that inview of the heavy sedation needed to control thecat during operation, properly administered generalanaesthesia is safer and preferable in all circumstanceswhere lumbar epidural block might beused in other species of animal.WILD FELIDAELarge zoological Felidae can usually be trapped in‘squeeze’ or transport cages and when properlyplaced in a ‘squeeze’ cage, a limb can usually beroped and pulled through the bars so that an intravenousinjection can be made. They may then betreated as large domestic cats and procedures arenot as difficult or hazardous as might be anticipated.If thiopental is used the dose should be keptto a minimum since recovery from its effects cantake up to 2 days in the larger animals such as lionsand tigers. Many lions and tigers in zoologicalcollections and circuses can be enticed up to thebars to have their backs scratched and, althoughsome caution is needed, s.c. injections can often bemade while they are apparently enjoying thescratching.If the animal cannot be approached closely,xylazine/ketamine or medetomidine/ketaminecan be administered i.m. by pole or projectilesyringe, taking care to use the shortest needlecommensurate with penetration of the skin.Needles should be large bore and have holes onthe side of the shaft, for ordinary open-endedneedles may block with a core of skin. It is advisableto have atipamezole readily availablebecause it is easy to over-estimate the weight ofanimals that cannot be weighed and it may befound that doses of xylazine or medetomidineused were excessive. Antagonism of ketamine isseldom needed because the safe dose range iswide.

THE CAT 461REFERENCESArnberg, J. (1979) Clinical manifestations of overdose ofketamine-xylazine in the cat. Nordiske VeterinaryMedicine 31: 155–161.Brearley, J.C., Kellagher, R.E.B. and Hall, L.W. (1988)Propofol anaesthesia in cats. Journal of Small AnimalPractice 29: 315–322.Chambers, J.P. and Dobson, J.M. (1989) A midazolamand ketamine combination as a sedative in cats.Journal of the Association of Veterinary Anaesthetists16: 53–54.Clarke, K.W. and Hall, L.W. (1990) A survey ofanaesthesia in small animal practice: AVA/BSAVAreport. Journal of the Association of VeterinaryAnaesthetists 17: 4–10.Davis, L.E. and Donelly, E.J. (1968) Analgesic drugs inthe cat. Journal of the American Veterinary MedicalAssociation 53: 1611–1667.Dunkle, N., Moise, N.S., Scarlett, K.J. and Short, C.E.(1986) Cardiac performance in cats afteradministration of xylazine or xylazine andglycopyrrolate: echocardiographic evaluations.American Journal of Veterinary Research 47: 2212–2216.Dyson, D.H., Allen, D.G., Ingwersen, W., Pascoe, P.J. andO’Grady, M. (1987) Effects of Saffan oncardiopulmonary function in healthy cats. CanadianJournal of Veterinary Research 51: 236–239.Evans, J. (1979) Steroid anaesthesia five years on.Proceedings of the Association of Veterinary Anaesthetistsof Great Britain and Ireland 8: 73–83.Garmer, L. N. (1969) Efects of 2-ethylamino- 2’-(2’phenyl) cyclohexanone HCl (CI-634) in cats.Research in Veterinary Science 10: 382–388.Gaynor, J.S., Dunlop, C.I., Wagner, A.E., Wertz, E.M.,Golden, A. and Demme, W. (1994) Morbidity andmortality associated with small animal anesthesia.Proceedings of the 5th International Congress of VeterinaryAnesthesia, Guelph, p. 173.Hall, L.W. and Taylor, P.M. (eds) (1994) Anaesthesia of theCat. London: Baillière Tindall.Hikasa, Y., Kawanabe, H., Takase, K. and Ogoasawara,S. ( 1996) Comparisons of sevoflurane, isoflurane andhalothane anaesthesia in spontaneously breathingcats. Veterinary Surgery 25: 234–243.Matot, I., Neely, C.F., Ray, M.D., Latz, R.Y. and Neufield,G.R. (1993) Pulmonary uptake of propofol in cats,effect of fentanyl and halothane. Anesthesiology78: 1157–1165.McMurphy, R.M. and Hodgson, D.S. (1994)Cardiopulmonary effects of desflurane in cats.Proceedings of the 5th International Congress of VeterinaryAnesthesia, Guelph, p. 191.McMurphy, R.M. and Hodgson, D.S. (1995) Theminimum alveolar concentration of desflurane in cats.Veterinary Surgery 24: 453–455.Sawyer, D.C., Rech, R.H. and Durham, R.A. (1991). Doesketamine provide adequate visceral analgesia whenused alone or in combination with acepromazine,diazepam, or butorphanol in cats Proceedings of the 4thInternational Congress of Veterinary Anaesthesia, Utrechtp. 381. Special Supplement to Journal of VeterinaryAnaesthesia 1993.Short, C.E. (1987) ‘Principles and Practice of VeterinaryAnesthesia. Baltimore: Williams and Wilkins, p. 550.Taylor, P.M. (1992) Use of Xylocaine pump spray forintubation in cats. Veterinary Record 130: 583.Taylor, P. M. (1993) Veterinary use of Xylocaine spray.British Journal of Anaesthesia 70: 113.Tranquilli, W.J., Thurmon, J.C., Speiser, J.R. Benson, G.J.and Olson, W.A. (1988) Butorphanol as apreanesthetic in cats: its effects on two commonintramuscular regimens. Veterinary Medicine83: 848–854.Verstegen, J., Fargetton, X., Zanker, S., Donnay, I. andEctors, F. (1991a) Antagonistic activities ofatipamezole, 4-aminopyridine and yohimbine againstmedetomidine/ketamine induced anaesthesia in cats.Veterinary Record 128: 57–60.Verstegen, J., Fargetton, X., Donnay, I. and Ectors, F.(1991b) An evaluation of medetomidine/ketamineand other drug combinations for anaesthesia in cats.Veterinary Record 128: 32–35.Verstegen, J., Deleforge, J. and Rossillon, D. (1994)Pharmacokinetics of ACP after single oraladministration in dogs and cats. Proceedings of the 5thInternational Congress of Veterinary Anesthesia, Guelph,p. 171.Watson, A.K. (1992) Use of Xylocaine pump spray forintubation in cats. Veterinary Record 130: 455.

Anaesthesia of birds,laboratory animals andwild animals17INTRODUCTIONThe problems involved in anaesthetizing birds,laboratory animals and wild animals for clinicalprocedures are usually much less complicatedthan those encountered when these animals areanaesthetized for experimental purposes where itis important that the method of anaesthesia shouldhave little or no influence on the result of the experiment.The techniques to be described in this chapterare those which the authors have found to be satisfactoryin general practice for most clinical purposesin the various species of animal presented to themand, except in fish, do not require drugs not generallyfound in most veterinary general practices.RODENTS AND OTHER SMALLMAMMALSAlthough rodents and other small mammals areanaesthetized in large numbers for laboratory procedureswith apparently few serious problems,when similar species are anaesthetized for clinicalpurposes the mortality is high. (In a survey by theAssociation of Anaesthetists of Great Britainand Ireland, 1 in 32 small mammals or birds anaesthetizedin small animal practices died.) The causeof the high clinical mortality probably results fromunfamiliarity with the species and the generallyless healthy state of the animals.Many small mammals become very distressedby handling, increasing the risk of physical damageand of adrenaline release leading to problemsunder subsequent anaesthesia. The risk of physicaldamage is considerably reduced by proper handlingand animals may be weighed with minimaldistress by placing them in a bag or small box hungfrom a suitable spring balance. Adequate preanaestheticexamination is often difficult but many haverespiratory disease so oxygen should be availableeven if only injectable agents are to be used. Thehigh metabolic rate of these small mammals meansthat they require an almost constant supply offood, so preanaesthetic fasting should not exceed3hours. There is no need to curtail the water supplyup to the time of induction of anaesthesia. Duringanaesthesia small mammals are particularly proneto hypothermia and precautions to avoid thisshould be taken. Removal of hair and wetting (particularlywith alcohol based preparations) shouldbe kept to a minimum; the animal should be placedon a heating pad during anaesthesia and recovery.Heat loss can be considerably reduced by wrappingthe animal in foil or bubble paper, althoughthis reduces the access of both surgeon and anaesthetistto the patient. When inhalation agents areused, carrier gases also contribute to coolingeffects, thus gas flows should be adequate but notexcessive. Adequate monitoring of the animal’scondition, including cardiac and respiratory functionand ensuring it is not hypothermic, is essentialuntil recovery is complete (Table 17.1).463

464 ANAESTHESIA OF THE SPECIESTABLE 17.1 Some physiological measurements in guinea pigs,hamsters,hens,mice,rabbits and rats.Values from various sources including Green,C.J.(1979) AnimalAnaesthesia. London:LaboratoryAnimals Ltd,and measurements made at Cambridge Veterinary SchoolWeight Heart rate Arterial BP Functional Tidal Minute Breaths/(kg) (beats/min) (mmHg residual volume volume minsyst/diast) capacity (ml) (ml) (l/min)Guinea pig 0.69 150 90/55 4.75 3.5 0.13 100range 0.43–1.05 130–190 4.1–5.1 1.0–4.0 0.08–0.40 90–150Hamster 0.1 350 150/110 0.8 0.06 90range 0.90–0.12 250–450 0.65–0.85 30–140Domestic hen 1.6 300 140/85 35 0.7 33Mouse 0.02 570 110/80 0.15 0.025 190range 500–600 100–250Rabbit 2.4 220 110/80 11.3 15.8 0.62 40range 2.05–3.00 205–235 7.2–15.8 11.5–24.4 0.37–0.89 32–53Rat 0.25 350 115/90 1.6 0.22 90range 0.2–0.3 260–450 1.40–1.75 0.21–0.30 70–150The commonest cause of death is respiratory failure.Ideally, O 2 and the ability to administer artificialventilation of the lungs should always beavailable. However, intubation of rodents requiresconsiderable practice as the narrow mouth makesvisualization of the larynx difficult. Suitable antagonistsshould be at hand and there may be a placefor analeptic agents such as doxapram in circumstanceswhere intubation is difficult. The othercommon cause of mortality is surgical blood lossso that care must be taken to minimize this and,whenever possible, to replace that which doesoccur, with plasma volume expanders (colloids) orRinger’s lactate solution.The use of anticholinergic premedication iscontroversial as in other species but as small airwaysare easily blocked by saliva or mucus, its useis often desirable. Doses of 0.04–0.05 mg/kg ofatropine are suitable for most rodents but rabbitsneed much higher doses (e.g. 1–2 mg/kg).Small mammals are generally poor subjectsfor local analgesia since even if this is effectivethey still require restraint. If used, localanalgesic drugs should be diluted and care takento avoid overdose. General anaesthesia is preferredfor most purposes and may be inducedand maintained with volatile agents, inducedwith injectabable drugs and maintained withvolatile agents, or maintained with injectabledrugs alone.ANAESTHESIA WITH VOLATILE AGENTSThe most popular agents are halothane and isoflurane.Ether, often used in the past, is not recommendedas the excessive bronchial secretions itprovokes may cause respiratory obstruction even ifan anticholinergic premedication has been given.Mask induction can lead to handling stress andthe use of an induction chamber is to be preferred.Several such chambers are commercially availablebut they are relatively easy to improvize and thereis no reason why they should not be available inmost general veterinary practices.Once induced, anaesthesia should be maintainedby volatilizing the volatile agent in a streamof oxygen and administering the mixture through aT-piece or similar low-resistance breathing system,taking care not cause hypothermia by excessiveflow rates. Suitable face masks for small rodentscan be made from plastic syringe barrels andshould not be a tight fit around the muzzle, forallowing gas to escape reduces resistance to breathing.Such a leak of gas does, however, constituteproblems of atmospheric pollution and some formof active scavenging of gases should be used.ANAESTHESIA WITH INJECTABLE DRUGSTheoretically, any injectable anaesthetic can beused in small mammals and usually the necessary

BIRDS, LABORATORY & WILD ANIMALS 465doses for healthy animals are well known from theoriginal developmental work in laboratory animalscarried out by the company concerned withmarketing the drug. However, practical limitationsare set by the possible methods of administration.In some animals with easily accessibleveins (e.g. in rabbits) drugs such as propofol orthiopental can be used as in cats and dogs(although the duration of effect may be shorter).Where i.v. injection is more difficult, drugs whichcan be given by i.p., i.m. or s.c. injection are generallyused. The most popular combinations of drugs arethe neuroleptanalgesics or mixtures incorporatingketamine. There are marked differences betweenspecies responses and even within one species ofanimal many drug actions may be unreliable, agiven drug producing deep anaesthesia in one animalwhilst only providing some sedation inanother of the same species.KetamineKetamine has the advantage that it is effective nomatter what the route of administration. Dosesrequired and efficacy vary greatly between thevarious species of animal. Lower doses may beused for sedation and immobilization for non-surgicalprocedures. As in other species of animal,ketamine is used in combination with drugs suchas the benzodiazepines (diazepam or midazolam)and/or α 2 adrenoceptor agonists (xylazine ormedetomidine) in order to reduce the dose of ketamine,improve muscle relaxation and to increasethe effectiveness of the dissociative agent as ananaesthetic. It is worth noting that the formulationsof ketamine at lower concentrations, whichare available for use in children, can prove moreconvenient for use in very small animals than thestandard veterinary preparation which needs to befurther diluted before use.NeuroleptanalgesiaAlthough most commercially available neuroleptanalgesiccombinations can be used, the mixtureof fentanyl and fluanisone (‘Hypnorm’) hasproved to be the most popular in the UK; it can beadministered by any route. The dose of fentanyl inHypnorm is high, resulting in a prolonged lengthof action and, occasionally, in respiratory arrest.Combinations of Hypnorm with diazepam ormidazolam give better muscle relaxation andallow a reduction of some 50% in the dose ofHypnorm. If anaesthesia becomes too deep thefentanyl component may be antagonized withnaloxone (0.1 mg/kg). Flecknell (1988) has reportedon the use of buprenorphine to antagonizethe fentanyl in the drug combination – the techniqueof sequential analgesia.Other agentsA mixture that is often used, although unlicensed, isknown as the ‘Hellabrunn Mixture’. It was developedprimarily for administration to zoo animalsand is prepared by adding 4 ml of ketamine(100mg/ml) to a vial of dry xylazine (500 mg). Thisyields a stable injectable solution containing xylazine125 mg/ml together with ketamine 100 mg/ml. Itsstability means that it is immediately available and itis relatively safe for the administrator.Alphaxalone/alphadolone (Saffan) has provedto be useful in some species of animal when giveni.v., and it may also be given i.m.Pentobarbital and thiopental may be used byi.p. injection in some animals but give prolongedsedation and respiratory depression; they cannotbe recommended for clinical use.AnalgesiaPostoperative analgesia must not be neglected.Some opioid drugs are suitable and other methodsutilizing local analgesics should be considered. Itis regrettable that the rat, which has probably contributedmore than most animals to advances inmedical and veterinary sciences, still seems inmany laboratories to be ignored in circumstanceswhere postoperative analgesia would be regardedas essential for other animals.LAGOMORPHSRabbits (Oryctolagus cuniculus) and hares(Lepus europaeus)Rabbits and hares need to be handled carefully;they tend to panic if placed on slippery surfaces

466 ANAESTHESIA OF THE SPECIESTABLE 17.2 Recommended doses of a variety of agents for use in rabbits.These are in accordance withthe majority of recommendations in the literatureDrug Dosage Route of injection ReferenceXylazine 3 mg/kg i.v. Flecknell (1988)+ +ketamine (3 min.later) 3 mg/kg i.v.Thiopental 10–12 mg/kg to effect i.v. Sedgwick (1986)Medetomidine 300 µkg s.c. Mero et al.(1989)Ketamine20 mg/kg+ +diazepan0.75–1.00 mg/kgMethohexital 5–10 mg/kg to effect i.v. Green (1975)Saffan 2–8 mg/kg i.v.for induction ofto effectanaesthesia only12 mg/kg i.m.(sedation only)Ketamine 20–60 mg/kg i.m. Clifford (1984)and are best held for injection wrapped in a towelin the arms of an assistant or placed in a restrainingbox. A rabbit or hare struggling against forciblerestraint may fracture a vertebra, so any restrainttechnique used should only entail the minimum offorce. They should be caught by grasping thescruff of the neck firmly and pressing down on aflat surface until they relax; they may then be liftedby supplementing the neck grip with support forthe hindquarters. Rabbits, especially when kept aspets, can be calmed by scratching behind the earsand stroking the back. Respiratory problems, usuallydue to pasteurella infections, are common inrabbits which may appear to be healthy, and auscultationof the lungs for diagnosis is not easy;many authorities advise thoracic radiographyprior to anaesthesia so that owners may be warnedof the anaesthetic risks associated with the presenceof lung disease.Intramuscular injections are made into thequadriceps or triceps or lumbar muscles. Intravenousinjections are given into the marginal veinof the ear and i.v. injection is greatly facilitated bythe use of a restraining box which leaves the earsaccessible.Endotracheal intubation is relatively difficultbecause of the long, narrow oropharynx and longincisor teeth limiting access through the mouth.The tongue is thick, fleshy, friable and easilytorn.The soft palate is long and the epiglottis islarge. Endotracheal intubation is either accomplishedby direct visualization of the larynx using astraight, premature human infant blade, or blindly.For blind intubation the the head should be held inextension on the neck to provide a straight line ofpassage for the tube. A semi-rigid stilette can beused as a guide to aid in the passage of the endotrachealtube. Tubes of 2.5 to 4.0 mm internal diameterare suitable for use in rabbits.Rabbits produce atropinase, which rapidly inactivatesatropine, so to be effective doses of this agentmust be high (1–2 mg/kg) and repeated every 15to 20 min. Alternatively, glycopyrrolate (0.01–0.02 mg/kg) may be used as an anticholinergic.Although i.v. anaesthetic agents can be used toinduce anaesthesia in rabbits (Table 17.2), they arenot good for maintaining anaesthesia for even verysmall incremental doses may cause death throughrespiratory arrest. Similarly, unexpected deaths mayoccur following ketamine or fentanyl combinations,but Scandinavian workers (Mero et al., 1989) havereported no deaths in a series of 340 rabbits undergoingexperimental surgery and anaesthetized by a s.c.mixture of medetomidine (300 µg/kg), ketamine(20mg/kg) and diazepam (0.75 to 1.50mg/kg).Induction of anaesthesia with thiopental (10 to12 mg/kg), methohexital (5 to 10 mg/kg) or Saffan(2 to 8 mg/kg) given i.v. to effect, is satisfactory butit is doubtful whether methohexital or Saffan haveany real advantages over thiopental. These agentsare best given i.v. through a 21 swg or 23 swg butterflyneedle strapped into an ear vein.

BIRDS, LABORATORY & WILD ANIMALS 467For an inhalation induction a 1:1 mixture ofN 2 O/O 2 should be administered through a facemaskfrom a T-piece system at a flow rate of about2 litres/min for 1 to 2 minutes before halothane orisoflurane is cautiously added in small step incrementsup to 2 to 3 %. Induction of anaesthesia isusually quiet when the volatile agents are vaporizedin the N 2 O/O 2 mixture in this way. Onceanaesthetized the rabbit may be intubated. Analternative method which is probably better if N 2 Ois not available is to place the rabbit in a box andintroduce a stream of halothane or isofluranevolatilized in O 2 into the box until the animal isunconscious. Anaesthesia is usually maintainedwith 1.5 to 2.0% halothane or 2 to 3 % isofluranegiven by face mask or through an endotrachealtube and, as always in rabbits, O 2 administration isessential since anaesthetized rabbits rapidly develophypoxaemia.The depth of anaesthesia is assessed by ticklingthe inside of the ear pinnae, since with manyanaesthetic methods the pedal withdrawal reflexmay remain strong until the animal is very close todeath. Loss of the corneal reflex is a sign of dangerouslydeep anaesthesia.Postoperative analgesia may be providedby buprenorphine (0.02–0.05 mg/kg s.c.) every8–12 hours, or pethidine (10 mg/kg s.c. or i.m.)every 2–3hours. Postoperatively, rabbits should bekept warm, e.g. in a baby incubator at 95 °F (35 °C).RODENTIARats (Rattus norvegicus)Rats that are not tame can be very difficult to handle;they cannot be restrained by the tail for anylong time for they will turn and climb up their owntails to bite the restraining hand. They can berestrained in a towel which is folded over the ratand rolled, making sure that the legs are secure.Experienced handlers often grasp the rat with thepalm of the hand over the animal’s back andrestrain the forelegs by folding them across eachother under the chin so that the chin cannot bedepressed enough to bite.There are very many ways of anaesthetizingrats but simple halothane or isoflurane anaesthesiais very satisfactory for all clinical purposes.TABLE 17.3 Injectable drugs for use in ratsDrug Dose Route ReferenceKetamine 50–100mg/kg i.m. Green et al.(1981)Ketamine 70–80mg/kg i.m. Flecknell+ + (1988)acepromazine 2.5mg/kg i.m.Ketamine 60–75mg/kg i.p. Nevalainen+ + et al.medetomidine 0.25–0.5µg/kg s.c. (1989)Ketamine 40–87mg/kg i.p.,i.m. Green et al.+ + (1981)Xylazine 5–13mg/kg i.p.,i.m.Hypnorm 0.4–0.5ml/kg i.m.or Greeni.p. (1975)Anaesthesia may be induced in a box used as aninduction chamber, or by face-mask, with theagent volatilized in a stream of O 2 . Injectableagents may be given i.v. into the dorsal metatarsalvein or a tail vein, or i.p.Ketamine is generally unsatisfactory in rats inthat i.m. doses of 60 mg/kg usually only producesedation. There are age and sex differences in theresponse of rats to ketamine. Duration of effectdecreases as young rats mature from 1 to 3 weeksof age. After 3 weeks females sleep longer thanmales. To produce anaesthesia in rats ketamineshould always be combined with other drugs suchas xylazine (Table 17.3).In inexperienced hands inhalation anaesthesiais safer and anaesthesia is best induced in a chamberalthough if contamination of the room air isignored it can be done by blowing the anaestheticgas mixture over the face through a face mask.Rats should be kept warm until full recovery isapparent and postoperative analgesia can beobtained from buprenorphine 0.1–0.2 mg/kg s.c.at 8 to 12 hourly intervals or pethidine 20 mg/kgs.c. at intervals of 2–3 hours.Mice (Mus musculus)Mice should be lifted by holding the base of the tailbetween the thumb and forefinger and immediatelytransferred to a horizontal cloth surface (e.g. thecoat of the handler). As it attempts to escape, it isgrasped by the loose scruff of the neck and the tail

468 ANAESTHESIA OF THE SPECIESTABLE 17.4 Drugs for use in miceDrug Dose Route DurationKetamine 100mg/kg s.c. SedationonlyKetamine 100–200mg/kg i.m. 60–100min.+ +xylazine 5–15mg/kg i.p. Sedation to100–200mg/kgis gripped, turning the animal so that its abdominalwall is presented for i.p. injections given 2–3mmfrom the mid-abdominal line. With skill, i.v. injectionscan be made into a lateral vein of the tailusing a 10 mm long 27 to 28 gauge needle. Themargin of safety is generally considered to be toosmall for the routine use of inhalation anaestheticssuch as halothane and isoflurane to induce andmaintain anaesthesia but methoxyflurane, whereit is still available, can be used with greater safety(Green, 1979). Assessment of anaesthetic depth isbased on the respiratory rate and depth, corneal,tail-pinch and pedal reflexes.As in rats, ketamine on its own is generallyunsatisfactory but it may be used with other drugs(Table 17.4). It is most important to keep micewarm whilst they are anaesthetized and in therecovery period.Guinea pigs (Cavia porcellus)competeanaesthesiaHypnorm 0.01ml/30g i.p. Approx.60min.Hypnorm 0.01–0.02mg/30g i.p.+ +diazepam 5mg/kg i.p. 60–90min.Guinea pigs are best restrained by graspingaround their pectoral and pelvic structures.They are not good subjects for anaesthesiawith injectable agents whether given by i.v. injectionor other parenteral routes. Visible veinsare fragile and venepuncture is often difficult,while the use of other routes necessitates an accurateestimation of body weight for computation ofthe dose. Since the gastrointestinal tract can contributeanything from 20 to 40% of the total weightof the animal, depending on its content of ingesta,it is not surprising that variable results followfrom i.p. or i.m. injections of computed doses ofinjectable drugs. Moreover, respiratory disease iscommon.Fortunately, halothane or isoflurane anaesthesiameets most of the needs of clinical practice. Amixture of the volatile agent with O 2 is supplied toan induction chamber (box) or face-mask at 1 to2l/min, starting with a minimal concentration andgradually increasing it until the animal loses consciousness.Anaesthesia is usually produced inabout 2 to 3 min and can be maintained with concentrationsof halothane (0.5 to 1.5%) or isoflurane(1 to 2%), given through a face-mask from a T-piece system. Full recovery follows in less than20to 30 min after termination of administration ofthe anaesthetic.Maintenance of a clear airway is not alwayseasy in guinea-pigs since nasal and oropharyngealsecretions tend to become viscid during anaesthesiaand are liable to give rise to obstruction. Therisk may be countered by frequent aspirationof the mouth and oropharynx using a fine rubbercatheter attached to a 60 ml syringe. Endotrachealintubation is virtually impossible unless a semirigidstilette is used as an introducer and a smallendotracheal tube (1.5 mm i.d) is threaded over itonce it is in the trachea. As with all small mammals,conservation of body heat is important and awarm environment should be provided.Ketamine, whether used alone or in combinationwith α 2 adrenoceptor agonists, immobilizesand produces anaesthesia in these animals(Table 17.5).TABLE 17.5 Drugs used in guinea pigsDrug Dose Route DurationSaffan 16–20 mg/kg i.v. 10–20 min.Saffan 40–45 mg/kg i.p.or 40–90 min.i.m. sedation onlyPentobarbital 30 mg/kg i.p. 60 min.Ketamine 30–44 mg/kg i.m. 75 min.sedation+ +xylazine 0.1–5.0 mg/kg i.m.Ketamine 40–100 mg/kg i.m. 60 min.+ + anaesthesiaxylazine 4–5 mg/kg i.m.

BIRDS, LABORATORY & WILD ANIMALS 469TABLE 17.6 Drugs recommended for use in hamsters and gerbilsDrug Dose Route Duration of effect ReferenceHamstersPentobarbital 70–80 mg/kg i.p. 60–75 min. Orland & Orland (1946)Ketamine 40–80 mg/kg i.m. Sedation only Green et al.(1981)Hypnorm 0.1 ml/kg i.p. 60 min. Green (1975)GerbilsPentobarbital 30–100 mg/kg i.p. Approx.60 min.Saffan 80–120 mg/kg i.p. Approx.75 min.Hamsters and gerbils (Mesocricetus auratusand Gerbillidae)It should be remembered that hamsters are nocturnaland often greatly resent being disturbedduring daytime, making them liable to bite. Thehamster’s scruff is quite loose so restraint bygrasping the scruff needs to be quite vigorous.Hamsters and gerbils are best anaesthetized byinhalation methods. They should be placed in aninduction chamber such as a small cardboard boxwith a perforated lid and anaesthetized withisoflurane or halothane introduced into the box ina stream of O 2 , using scavenging of emergentgases whenever possible. The animal is removedfrom the box as soon as it becomes unconscious.Unconsciousness is usually equated with loss ofthe righting reflex when the box is tilted; anaesthesiais then maintained using a face-mask. If the useof injectable agents is obligatory, neuroleptanalgesiccombinations appear to give the most reliableresults. Ketamine is very variable in effect(Table 17.6).Mink (Mustela vison)Mink are not domestic animals – they are nervous,fast and vicious. All mink are best handled bypersuading them to enter a clear sided inductionbox. Mink dislike a human blowing into theirface and will retreat from such an onslaught.Moreover, mink are very inquisitive and willinvestigate the source of gentle scratching noisessuch as can be made on the side of a box. Once inthe box they can be anaesthetized with a volatileanaesthetic such as isoflurane or halothane. If necessarythe box may be covered with transparentplastic sheeting to make it more gas-tight, anduntil it is unconscious the animal is not removedfrom the box.Ferrets and skunks (Mustela putorius furo;Mephitis mephitis)Ferrets are tractable and are usually easily tamed.They readily vomit when anaesthetized so theyshould be fasted for about 6 hours before inductionof anaesthesia. Skunks can spray the anaesthetistwith musk unless precautions are taken to avoidthis. The scent glands can be emptied by holdingthe skunk up with its hindquarters away from thehandler and pulling the tail up and forwardstowards the head.Ferrets and skunks can be anaesthetized withisoflurane or halothane passed into an inductionbox until they are unconscious, following on withthe administration of the agent through a face-maskfrom a T-piece system. Skunks are probably bestanaesthetized in a disposable clear plastic bag,surgery being performed through a hole cut in thebag At the end of the procedure the bag is discarded,eliminating the problem of persistent odour otherwiseprobable when a box is used. Inhalation anaesthesiapresents no special features in these animals.Stoats and weasels (Mustela erminae;Mustela nivalis)Stoats and weasels can be dealt with in a similarmanner, using an induction box, but it should beremembered that they are much more vicious thanferrets or skunks. Preferred injectable agents arei.m. ketamine 20–30 mg/kg or ketamine (25 mg/kgi.m.) with diazepam (2 mg/kg i.m.) or Saffan(10–15 mg/kg i.m.).

470 ANAESTHESIA OF THE SPECIESOTHER SMALL MAMMALSBadgers (Meles meles)Badgers resist handling by biting and scratching.The safest procedure for handling them is toimmobilize them with ketamine (10–20 mg/kgi.m.) prior to maintenance of anaesthesia with conventionalinhalation techniques.Hedgehogs (Erinaceus europaeus)Hedgehogs are usually given drugs i.p. or anaesthesiais induced in a chamber with a volatileagent. Hypnorm, the fentanyl-fluanisone mixture(0.2 ml/kg) together with diazepam 2.5 mg/kg,both given i.p. are said to be the most useful agentsin this species of animal. However, to give an i.p.injection the animal must first be made to unroll byprodding it on the rump or back of the neck. As itunrolls the strong spines on the crown of the headare grasped with stout artery forceps and used togently rock the animal up and down until ituncurls. Keeping the hind limbs pinioned thenprevents it rolling itself up.CHELONIAIn tortoises, terrapins and turtles anaesthetic problemsare posed by the very low metabolic ratewhich varies with environmental temperature andthe ability to retract the head into the protectiveshell. Some species present further problems dueto their adaptation to a semi-aquatic or aquaticmode of life. It should be remembered that somespecies of soft shelled turtles can move quicklyand handlers can be bitten or scratched.The lungs are well developed and the respiratorymovements are produced chiefly by musclesat each leg pocket beneath the viscera. Althoughthese muscles have been described as diaphragms,they are too weak to drive gases around any anaestheticsystem. Most chelonians have the ability tosurvive on a single respiratory movement perhour, making attempts to induce anaesthesia withinhalation agents rather unsuccessful.Ketamine is probably the anaesthetic agent ofchoice although it does not produce muscle relaxation.It may be given in doses of 60 to 80 mg/kginto gluteal muscles and if the sedation producedis not sufficient for surgery it may be deepened byadministration of isoflurane or halothane becausethe head will protrude from the shell and breathingwill be reasonably rapid. Saffan may be usedinstead in i.m. doses of 12 to 18mg/kg. Loss of muscletone in the neck is the best guide to the depth ofcentral nervous depression. Chelonia are easilyintubated.Recovery from a dose of 60 mg/kg of ketaminetakes up to 24 hours. Tortoises should be allowedto recover at normal room temperature, preferablyin a straw filled box. Terrapins and turtles shouldbe kept at a slightly lower environmental temperatureand have their bodies kept damp by the applicationof cold water at frequent intervals.REPTILIASnakes are difficult subjects for the anaesthetist.They have a low basal metabolic rate which isdirectly related to the environmental temperatureso that if parenteral agents are used the inductionand recovery times are very variable. Moreover,they are relatively resistant to hypoxia and canhold their breath for several minutes so that theinduction of inhalation anaesthesia may be veryprolonged.Snakes have peculiar anatomical features. Theabsence of an epiglottis and the position of theglottis makes it possible to intubate non-venomoussnakes under simple physical restraint andinhalation anaesthesia may then be induced by theuse of IPPV (Fig. 17.1). (Even so, non-venemoussnakes can still inflict bite wounds which oftenbecome septic!) Most snakes have only one functionallung which consists of a thin walled tube terminatingin an air sac extending to the level of thecloaca, the trachea being open along one side withinthe lung. There is no diaphragm and the threechambered heart yields a slushing noise instead ofthe clear ‘lub-dub’ of the mammalian heart onauscultation.Snakes appear to be extremely sensitive topainful stimuli and strike or contract violentlywhen an injection needle is inserted through theskin. It is, therefore, essential to have snakes properlyrestrained before attempting any injection. A

BIRDS, LABORATORY & WILD ANIMALS 471EyeBodyLarynxTongueFIG.17.1 Intubation of snakes.Once the mouth isopened widely the larynx is visible and endotrachealintubation presents no problems.simple aid to handling is to reduce the environmentaltemperature to below 10 °C for this makesthe poikilothermic snake very sluggish. Ifinjectable agents are to be used only the lightestlevel of narcosis compatible with safe handlingshould be used, for deeper levels which requirelarger doses of drug may be followed by a recoveryperiod extending over several days.Of the injectable central nervous depressantsonly ketamine is really useful and initial i.m. dosesof the order of 50 mg/kg produce moderate sedationwhich facilitates handling but muscle relaxationis poor and serpentine movements mayoccur. Ketamine anaesthesia can be supplementedby infiltration of the surgical site with 0.5 to 1.0%lignocaine, or by the administration of isofluraneor halothane after endotracheal intubation.Snakes may also be anaesthetized with inhalationanaesthetics when a rapid recovery is important.Induction is best achieved by placing thesnake in a clear plastic box, strong plastic bag or anaquarium tank into which 7 to 10% halothane orisoflurane vapour in oxygen or nitrous oxide/oxygenis piped. Induction may take as long as 15 minutesand the snake should not be removed untilagitation or turning of the container demonstratesthat righting reflexes have been lost. It is thenremoved, intubated and anaesthesia maintainedwith about 3% of halothane or 4% of isofluranevapour given with IPPV. Lung ventilation shouldbe at the rate observed in the previously consciousindividual and fluid balance should be maintainedby giving 5 ml of isotonic saline every 1–2 hours.Most snakes may be kept at normal ambient temperaturesof around 20 °C unless it is desired tocool them for restraint purposes.Induction of anaesthesia in a tank has theadvantage that venomous snakes can be anaesthetizedwith the minimum of handling, butbecause anaesthetic vapours are heavier than airthey sink towards the bottom of the tank andsnakes can raise their heads above the anaestheticlayer so delaying the onset of anaesthesia. It isalways wise to ascertain the righting reflexes reallyhave been abolished before removing the snakefrom the tank.Most snakes exhibit a short period of excitementor agitation when first exposed to an anaestheticvapour but they quieten down and it is notalways easy to ascertain the depth of anaesthesia.The first indication that the snake can be safelyremoved from the tank is certainly loss of rightingreflexes but the tail withdrawal reflex is also valuable.Absence of response to pricking of the tailindicates that surgical anaesthesia is present. If thetip of the tongue is gently grasped with forcepsthere is a marked resistance to its withdrawal untilthe stage of surgical anaesthesia is reached.FISHFish are usually anaesthetized by allowing them toswim in a solution of the anaesthetic agent. Thesolution should be made up in some of the waterin which they are normally maintained (NOT intap water which is often heavily chlorinated) andvarious drugs are used:1. Carbon dioxide may be used at aconcentration of 200 ppm.2. Diethylether 10–15 ml per litre of water isusual but 50 ml per litre of water has been used forlarge fish. In goldfish anaesthesia is induced inabout 3–5 minutes; recovery once placed inanaesthetic-free water takes 5–15 minutes.3. Tricaine methanesulphonate is probablythe best agent to use. It is a white powderwhich dissolves in both fresh and sea water.

472 ANAESTHESIA OF THE SPECIESConcentrations of 1:30 000 up to 1:1000 areemployed, the more concentrated solutions beingused for larger fish. Anaesthesia is induced in1–2minutes and fish recover once placed in nonmedicatedwater in about 15 minutes.4. Propoxate hydrochloride (R7464) is verysoluble in both fresh and sea water. It is used inconcentrations of 0.5 to 10.0 ppm to obtain varyingdegrees of depth of central nervous depression.Unfortunately, propoxate is difficult to obtain.5. Benzocaine in an immersion solution atconcentrations of 20–30 ppm is an excellentanaesthetic for tagging, marking and measuringfish (Laird & Oswald, 1975). For surgical anaesthesia50 ppm solutions are used. It is dissolved inacetone at 40 mg/ml giving a stable solutionwhich, if protected from light, will keep for up to 3months. For use, this concentrated solution isdiluted in fresh or sea water as required.When a fish is immersed in the anaesthetic solutionthere is initial excited swimming, becomingincreasingly erratic. The fish then becomes inactive,sinking to the bottom of the container to reston its back. For surgery, the fish is removed fromthe tank and placed on a moist cloth. Completerecovery from the effects of the anaesthetic ensueswhen the fish is place in clean, aerated water (freshor sea water but NOT tap water).BIRDSIn recent years interest in conservation of wild lifehas led to an increased demand for anaesthesia forsurgical purposes in wild or semi-wild birds aswell as the more domesticated chicken, duck orgoose. Cage birds have also become popular ascompanions, especially for elderly people living inurban districts, and as a result of these trends it isnow commonplace for the veterinary anaesthetistto be confronted with avian patients requiringanaesthesia for a wide variety of conditions. It iswell known that birds do not react in the same wayas mammals to stimuli which in man cause pain.For example, after a slight reaction to the skin incision,conscious birds do not show any response tothe manipulations involved in caponization. Manyoperations on hens, such as the suturing of a torncrop or the removal of superficial neoplasms,cause little response and the heart rate, which mightbe expected to increase if pain was experienced,remains normal. In spite of these differences humaneconsiderations seem to dictate that anaesthesiashould be used for birds as it is for mammals.The special problems presented by birds, especiallywild ones, are related to their physiological,anatomical and metabolic differences from mammals.The problems of handling wild birds areoften greatly exaggerated. Provided they are handledquietly and that the normal precautions aretaken (such as the wearing of gauntlets when dealingwith birds of prey), few difficulties or dangersare encountered.The high metabolic rate has several implicationsfor the anaesthetist. It implies a higher rate ofutilization of foods so that starvation of 6 to 8hours is often sufficient to produce fatal hypoglycaemiaand ketosis. Metabolism of parenterallyadministered agents is also rapid. The high avianbody temperature means that excessive coolingoccurs when the bird is exposed to a cool environmentduring or after anaesthesia, especially ifmany feathers are plucked around the operationsite. Small birds such as budgerigars have veryhigh, labile heart rates and heart failure is frequentlyencountered when these birds are frightenedby handling. The blood volume of birds issuch that small surgical haemorrhages may be sufficientto cause death from shock.The avian respiratory tract is very differentfrom that of mammals, one obvious differencebeing that inspiration in birds is normally passivewhilst expiration is active. The respiratory systemis constructed around a central ‘core’ of relativelyfixed lung volume and its anatomy has been welldescribed by Dunker (1972), Piiper (1972) andPiiper and Schneid (1973). The trachea divides intotwo mesobronchi which in turn divide to give secondarybronchi, one group of which, the ventrobronchi,communicates with the cranial air sacs(cervical and interclavicular). The dorsal andlateral secondary bronchi arise from each mesobronchusbefore these terminate in caudal air sacs(abdominal and posterior thoracic air sacs). Thedorsal and ventral bronchi are joined by narrowtubes, the parabronchi, which form the analogueto mammalian lungs and are where gaseous

BIRDS, LABORATORY & WILD ANIMALS 473exchange takes place between the air and theblood. Air passing through the parabronchi movesin one direction only during both inspiration andexpiration: blood flows across the direction of gasflow. Thus, the gas composition must change fromthe inspiratory to expiratory ends of theparabronchi so that capillary blood must equilibratewith parabronchial gas at widely differentPO 2 and PaCO 2 . The arrangement is such that gasexchange takes place during both inspiration andexpiration and its efficiency is dependent on anuninterupted flow of air through the lungs. Tidalexchange is generated through the air sacs andfluid such as blood or injected solutions will interferewith ventilation. Even short periods of apnoeaare serious and will produce marked hypoxia.Anaesthetic gases and vapours are rapidlyabsorbed into the blood stream so that induction ofanaesthesia is rapid when inhalation anaesthesia isused and, equally recovery is also rapid. Mostinhalation anaesthetics are less soluble in in avianthan in mammalian blood so that brain tensionsequilibrate more rapidly with lung tensions andthe clinical anaesthetist will often find inductionand recovery disconcertingly abrupt.After anaesthesia birds must be kept warm in adarkened, padded box and they should be supportedin sternal recumbency. During recoveryvigorous flapping of the wings may occur and thisshould be prevented by wrapping the bird in atowel because a wing bone may be fractured if thewing beats against the cage or box wall.ANAESTHETIC TECHNIQUESLocal analgesiaBecause birds such as budgerigars are so small it isvery easy to give a gross overdose of a local analgesicagent, but in larger birds local analgesia canbe used quite safely. Even so, in large birds it iswise to watch the total dose which is administeredand to use very dilute solutions (e.g. 0.25–0.50%lignocaine) for injection because there is some evidencethat birds are more sensitive to local analgesicsthan are mammals of the same body weight.Many workers consider that local analgesia has noplace in avian anaesthesia because even when correctlyused the bird still requires restraint and thismay produce undue distress.Injectable agentsWhenever possible birds should be weighedbefore any drug is given by injection. This is usuallypossible if the bird can be confined to a plasticbox. Physical restraint should be kept to a minimumbecause small birds such as budgerigars andcanaries are prone to become very distressed andlarge birds may fracture bones whilst trying toescape. Poultry should be grasped so that thewings are held back along the abdomen to quietenthem. Budgerigars and the like should be cradledin the palm of the hand with the neck between theindex and middle fingers, taking care not to applypressure to the neck. Hawks usually present noproblem after being hooded and parrots may begripped around the neck and wings with a handwrapped in thick towelling.Intramuscular injection is made into the pectoralmuscles on either side of the cariniform sternumor into the thigh muscles. Intravenousinjections are made into the brachial vein where ispasses over the ventral aspect of the elbow joint.Although very many injectable agents have beenused in birds of all kinds it is probable that ketamineis the one of choice in every case (Table 17.7).When an injectable agent has to be used ketaminemay be given i.m. in doses of 15 mg/kg. The birdshould be confined in a warm, darkened boxTABLE 17.7 Doses of ketamine and ‘HellabrunnMixture’ for various birds.(Data from severalsources but mainly from published data sheets,Bayer UK Ltd and Parke-Davis Veterinary)Bird Adult Ketamine ‘HellabrunnBW (g) dose (mg) Mixture’(ml/kg)African Grey 350–450 10–14 0.02parrotsBudgerigars 30–50 2 –Geese 5000–7000 60–85 0.03–0.08Gulls 500–800 12–15 0.030–0.035Kestrels 150–250 6–8 0.03–0.06Macaws 750–850 15–18 0.020–0.025Muscovy 3500–5000 35–50 0.02ducksParakeets 80–100 3 0.03Penguins 3200–6000 70–175 0.06Mute 6000–7000 70–85 0.03–0.06swans

474 ANAESTHESIA OF THE SPECIESas soon as the injection has been made and thedepth of anaesthesia produced is assessed by notingresponse to pinching the wattle or skin of theneck and although the eyelids often close thecorneal reflex should persist throughout.Increments can be given to produce the desireddegree of unconsciousness. There is a wide safetymargin and doses of 25 mg/kg of ketamine maysafely be given to all species of birds, althoughrecovery may sometimes be prolonged.Inhalation anaesthesiaWhenever possible it is probably desirable toinduce and maintain anaesthesia with an inhalationagent. Birds may be restrained so that anaesthesiacan be induced using a face-mask or theycan be confined in a box made of transparent plasticmaterial while anaesthetic gases or vapours areintroduced into the box. Probably the best methodis to induce anaesthesia by passing halothane orisoflurane into the box in which the bird is confinedand then to maintain anaesthesia by administeringthe same agent through a face-mask orendotracheal tube.Endotracheal intubation is not difficult in birds(Fig. 17.2) and suitable tubes may be constructedfrom silicone rubber or PVC tubing. Tubes shouldbe long enough to reach the syrinx but deadspacemust be kept to a minimum and their ends shouldbe be cut at a bevel to facilitate passage into the trachea.Airway secretions may block the flow of gasin both intubated and non-intubated birds so it isalways wise to have suction available for theirremoval by aspiration. Adequate suction can beprovided from a 60 ml syringe fitted with a shortlength of fine catheter.Most birds can be anaesthetized with 0.5–1.0 %halothane or 1.0–1.5% isoflurane vapour in oxygendelivered to the endotracheal tube or facemaskfrom a T-piece system. The air sacs should beflushed at about 5 minute intervals by occlusion ofthe open arm of the T-piece system, their overdistensionbeing prevented by escape of gas aroundthe loose-fitting endotracheal tube or by partiallifting of the facemask away from the face.Totalgas flow rates should be about two to three timesthe estimated minute volume of respiration of thebird, e.g. about 750 ml in an adult domestic hen,FIG.17.2 Larynx of a raptor – to demonstrate theaccessibility for endotracheal intubation.250 ml in a pigeon and 25 ml in a budgerigar.Inhalation anaesthetics may also be administeredthrough a needle introduced directly into an airsac, but this has litle to commend it.Recovery from anaesthesia is accelerated byadministering oxygen and flushing the air sacsfrom time to time until the bird has regained itsrighting reflexes. Unless this is done the anaestheticwhich passes into the air sacs may not becleared by the depressed respiratory activity sothat it will be taken up again by the parabronchialcapillary blood and recovery will be prolonged.Combinations of inhalation and injectableagentsVery satisfactory results are obtained by the combinationof injectable and inhalation agents.

BIRDS, LABORATORY & WILD ANIMALS 475Although many combinations have been used, theinduction of unconsciousness with ketamine(10–15 mg/kg i.m.) followed by the inhalation ofisoflurane/O 2 or halothane/O 2 is probably thesimplest and safest.Measurement of ketamine doses for small birdssuch as canaries and budgerigars which mayweigh from 30 to 60 g is not easy and these birdsmay be dosed with 1 to 2 mg per bird. The standardsolution of ketamine for veterinary use contains100 mg/ml and if 0.1 ml is diluted to 1 mlbirds may be given 0.1–0.2 ml of the diluted solutioni.m. into the pectoral muscles. The larger dose(0.2 ml of the diluted solution) will usually producelight anaesthesia in 2–3 minutes from thetime of injection.It has been claimed, often anecdotally, thatcertain species of birds including moorhens,coots, doves and vultures are unsuitable for anaesthesiawith ketamine on its own or in combinationwith other drugs. Saffan can be used in placeof ketamine for most birds but when given i.m. itproduces more variable results, probably dueto the difficulty of ensuring that the dose is correctlyadministered into a muscle mass. Theaim should always be to give just enough ofthe injectable agent to make the bird unconsciousand to use only as much isoflurane orhalothane as is necessary for the maintenance ofanaesthesia.RATITESOstriches and emus pose challenging problems forrestraint. Adult birds can move very quickly, peckwith great accuracy and have large-toed feetwhich they use to strike forwards. Handling can befacilitated by hooding and it is always wise, wheneverpossible to work with attendant(s) familiarwith these flightless birds. Ketamine (15 mg/kg i.m.)appears to produce the most reliable andsmoothest induction of anaesthesia, especiallywhen combined with diazepam (0.5 mg/kg i.m.)or xylazine (3.5mg/kg i.m.). Inhalation anaesthesiacan be maintained in emus and ostriches weighingless than 130 kg using small animal breathingsystems, but a large animal breathing system isneeded for larger birds.BEARSBears can inflict severe injuries; their faces are curiouslyexpressionless and it is difficult to detecttheir mood. Even a playful blow from a paw caninflict a severe injury. Grizzly and polar bears maydeliberately attack human beings.In zoos and circuses, they can be confined insqueeze cages or airtight boxes where injected orinhalation agents can be administered, but if thesefacilities are not available, ketamine can be administeredfrom a projectile syringe (see below). Dosesare not well established but various doses from 15–25 mg/kg have been administered safely, withatropine to control salivation. Suggested optimaldoses are i.m. xylazine (2.9 mg/kg) plus i.m. ketamine(2–9 mg/kg) but it should be noted thatyoung bears seem notably sensitive to sedationand should have reduced doses.Venepuncture is not easy, even in sedated bears,because the limb veins are small and embeddedin fat so that if sedation produced by ketaminedoes not allow surgery an inhalation agent suchas halothane or isoflurane should be given.Endotracheal intubation is not difficult in theunconscious animal.NON-HUMAN PRIMATESNot only can monkeys inflict bites and scratches,they are also carriers of viruses which are extremelypathogenic to man as well as diseases such astuberculosis, salmonellosis and shigellosis. Forthese reasons it is always undesirable to handleconscious monkeys, and even domestic petsshould be viewed with suspicion. Handling ofany pet monkey should, preferably, be left to itsowners.If the owner of a small pet monkey can beinduced to hold its arms behind its back the anaesthetistcan usually make an intravenous injectionof an anaesthetic such as thiopental or Saffan intothe recurrent tarsal vein on the dorsal surface ofthe gastrocnemius muscle. Caution is necessaryfor these monkeys often weigh much less than isestimated and it is seldom necessary to exceed5mg/kg of thiopental or 2 mg/kg of Saffan. Once

476 ANAESTHESIA OF THE SPECIESunconscious the monkey may be given a smalldose of suxamethonium (e.g. 1 mg/kg) and intubatedwith an uncuffed tube. Anaesthesia maythen be maintained by the administration ofhalothane or isoflurane in N 2 O/O 2 , or O 2 alone,from a T-piece system. When suxamethonium is tobe given it is wise to inject atropine (0.15–0.30 mgi.v.) as soon as the induction agent has been given.Alternatively, if the owner or an assistant canhold the monkey, again with its arms held behindits back, an inhalation agent can be used for bothinduction and maintenance of anaesthesia. Theuse of N 2 O is a distinct advantage in these circumstancesand halothane is probably the volatileagent of choice for, in the authors’ experience,isoflurane often provokes breath holding. A suitableface-mask is held over, but not touching, theface and N 2 O/O 2 (3:1) is administered at a flowrate of 4 l/min for 1–2 minutes. Halothane is thenintroduced into the gas mixture, increasing theconcentration of the vapour every 3 to 4 breaths toa maximum of about 3%. The mask is applied tothe face as soon as it is judged that the monkey isunconscious and induction is usually free fromexcitement and struggling. Scavenging of wastegases is usually not possible during the inductionof anaesthesia. Anaesthesia is maintained with1.2– 1.5% of halothane vapour in the N 2 O/O 2mixture.Larger or less co-operative monkeys may needsedating by i.m. injection before an attempt is madeto induce anaesthesia (Green, 1979). The use ofprojectile syringes is not to be recommended formonkeys are adept at dodging or even deflectingthe projectile with their hands, and they usuallypull the needle out before the injection is completeeven when a hit is obtained! In the case of thesmaller varieties it is usually possible to catch themonkey’s arm through the bars of the cage so thatinjection can be made into the deltoid muscle, buta squeeze cage may be needed for the larger,strong animals such as adult chimpanzees.Ketamine is probably the agent of choice in allexcept squirrel monkeys and marmosets for chemicalrestraint or preanaesthetic sedation. At doserates of 10–25 mg/kg the volume of the veterinarypreparation ‘Vetalar’ injected is small so that thedrug can be given rapidly into the thigh muscles ofeven struggling animals. The peak effect isobtained 5 to 10 minutes after injection and theperiod of sedation is from 30 to 60 minutes.Recovery is complete in 1.5 to 4.5 hours dependingon the dose and species of the monkey. When thedesired degree of sedation is not produced by ketaminefurther depression of the central nervoussystem is probably best produced by administrationof N 2 O/O 2 supplemented with 0.5 to 1.0%halothane delivered through a face-mask from a T-piece system.For squirrel monkeys and marmosets Saffan isthe sedative of choice and this preparation is alsouseful in other species of non-human primates. Insquirrel monkeys and marmosets doses of 15–18mg/kg produce light general anaesthesia some5 minutes after injection into the thigh muscles.Anaesthesia lasts about 45 minutes and is followedby recovery to full consciousness 1–3 hours later.In baboons, i.m. doses of 12–18 mg/kg make theanimal safe to handle about 10 minutes after injectionand recovery is much quicker than in squirrelmonkeys. In all monkeys anaesthesia may bedeepened by giving i.v. increments of Saffan untilthe desired depth is obtained. Animals can then beintubated and maintained unconscious withinhalation agents such as halothane, or sequentialincremental i.v. doses of Saffan can be given overseveral hours if need be. The main disadvantage ofSaffan is the large volume which has to be giveni.m., although these volumes do not appear toresult in pain at the injection site.When it is impossible to give an i.m. injection to alarge monkey or ape the simplest thing is to enticeit into a cage which can be made airtight by coveringwith a sheet of plastic material so that anaestheticgases and vapours can be piped in. Theanimal must be observed carefully and removedfrom the cage as soon as it is unconscious andrelaxed.It is important to conserve body heat and theanaesthetized monkey should be placed on awarm water blanket maintained at 38 °C; this isespecially important for small monkeys. If sedationor anaesthesia is to last for more than about anhour, an intravenous drip infusion of N/5 saline orHartmann’s solution (Ringer’s lactate) should bestarted as soon as the animal is anaesthetized orsufficiently sedated. The fluid should be given atthe rate of 10 ml/kg per hour and, for the smaller

BIRDS, LABORATORY & WILD ANIMALS 477monkeys it should be warmed to 38 °C by passingit through a blood warmer before it reaches theanimal. The use of atropine is somewhat controversialbut it is probable that it should be given assoon as the monkey becomes anaesthetized, in adose of 0.15 to 1.20 mg depending on the size of theanimal.Recovery from anaesthesia should take place ina warm environment and endotracheal tubes andi.v. cannulae must be removed while it is still safeto handle the animal. Postsurgical analgesiashould be provided by the i.m. injection of a suitableanalgesic (e.g. pethidine at 2 mg/kg or morphineat 0.1 mg/kg).WILD ANIMALSOnly species of wild animal which are likely to beencountered by those in general veterinary practicein the UK will be considered here, but as a generalrule the principles of anaesthesia as applied todomesticated or captive pet animals apply equallywell in all wild animals and the main differencesarise from the need to protect the anaesthetist andany assistants from injury by unanaesthetizedsubjects.Difficulty in getting close to the subject, eitherbecause of its timidity or aversion to mankind, andthe obvious need to avoid being attacked, have ledto two approaches to the problems. The first is theuse of squeeze cages, the animal being enticed intothe cage then squeezed between a fixed and movablewall so that cannot turn around or move veryfar whilst being given an injection of a sedative oranaesthetic agent. These cages should be standardequipment at zoos, some research centres and similarestablishments and they have a definite role inthe capture of farmed deer, but they are unlikely tobe available to the veterinarian in general practice.The second which is, perhaps, more generallyapplicable, is the administration of agents fromprojectile syringes. These syringes may be projectedfrom rifles, crossbows, or blow-pipes so that theadministrator can remain a safe distance fromthe subject (Fig. 17.3). They were originally developedfor the capture of wild game animals but theyare now finding a use in ordinary veterinary practicewhere, for example, current methods of farming(particularly of some European breeds of cattle)are producing virtually unhandled beasts whichare often aggressive, especially if frightened.The use of projectile syringes for the captureand restraint of wild game animals was wellreviewed by Harthoorn (1971). The problems relatedto the use of projectile syringes in general veterinarypractice are somewhat different.Theprojectile syringe is designed to inject its contentsafter the needle has penetrated the skin of the animaland its impact with the tissues can result inserious bruising. They should empty within secondsof penetration and the force of the injectionshould be adequate to push the plunger fullyhome even if the needle is partially obstructed by askin plug. To minimise tissue damage the syringeshould strike the beast towards the end of the firingtrajectory, although obviously this is lessimportant when the projectile is propelled from ablowpipe. When fired from a gun or cross-bow attoo close range the syringe needle may enter bodycavities, and often when striking too hard,syringes bounce off without penetrating effectivelyin spite of barbs and collars on the needles.Extensive and fatal trauma may be caused byinjection into the thoracic or abdominal cavities.In all cases the shortest needle commensuratewith penetration of the skin should be used andlarge bore needles should terminate in a cone, withholes on the side of the shaft, for the ordinaryopen-ended needle may block with a core of skin.Collared needles are seldom satisfactory and tendto allow fluids to flow back out of the hole causedby penetration of the collar. To remove a barbedneedle a small incision is made over the site of thebarb.Irritant solutions may not be used since theiradministration under the non-sterile conditionsassociated with the use of dart-guns may producean abscess, but when simple precautions are routinelytaken, untoward reactions at the site of injectionare surprisingly rare. Valuable animals maybe given a precautionary dose of antimicrobialsubstances and in summer the wounds should bedressed with fly repellents.There are now many patterns of projectilesyringes designed for use with rifles, pistols andcross-bows but, in general, they usually inject theircontents through the agency of an explosive cap

478 ANAESTHESIA OF THE SPECIESand striker mechanisms, or by gas evolved from achemical reaction initiated in a capsule by a similarstriker mechanism, incorporated behind thesyringe plunger. The projectiles used with blowpipeshave needles with side holes which arecovered by a short plastic sleeve and displacementof this sleeve as the needle penetrates the skinand its displacement allows the pressure of airor gas previously injected behind the plunger toinject the syringe contents. In projectiles firedfrom crossbows, rifles or pistols detonation ofan explosive cap produces such a force that theejected fluid penetrates far into the tissues andhaematoma formation is common so that the slowerinjection due to gas propulsion is usually to bepreferred.Projectile syringes usually have a capacity of upto 4–5 ml so that only relatively soluble drugs canbe administered. If they are to be used on commonland or in dense undergrowth any temptation touse Immobilon or etorphine should be resisted forshould the projectile bounce off the animal or theanimal be missed completely, these projectiles aresurprisingly difficult to locate in spite of theirbright silver barrels and coloured flights, and theirsubsequent discovery by a child or even an adultcould have fatal consequences for that individual.It must be appreciated that projection is very farfrom accurate. The weight of the projectile accordingto its capacity and degree of filling has a greatinfluence at all but the shortest of ranges whichcan, in any case, only be estimated. Experience hasshown that the best results are obtained by gettingas close to the animal as is possible or safe, andaiming for the neck or shoulder region.FIG.17.3 ‘Dist-Inject’ dart pistol with projectile syringe.The lower illustration is of the ‘Miniject’ projectile syringefor use with a blowpipe.It is always advisable to use doses of injectableagent which allow the animal to be approachedwith safety and so allow general anaesthesia to beproduced with i.v. or inhalation agents. Althougha quick recovery is essential in the wild, as partiallysedated animals are at risk from predators, it is notso important in captive animals. To date, the techniquesmost frequently used for immobilizing awide variety of species have been based on useof opioids such as etorphine or carfentanil coupledwith sedatives, anaesthesia being terminatedwith antagonists such as diprenorphine or atipamezole.Ketamine and ketamine combinationsare now being employed much more commonly inruminants.The doses of drugs required by various speciesof animal and breeds within a species varies enormouslyso that an extensive literature on the subjectis now available. Anyone wishing to make useof agents to be administered by projectile syringeis strongly recommended before doing so to consultsuitable literature available from commercialsources.REFERENCESCooper, J.E. (1989) Anaesthesia of exotic species.In: Hilbery, A.D.R. (ed.) Manual of Anaesthesia forSmall Animal Practice. Cheltenham: BritishSmall Animal Veterinary Association, ch. 17,pp. 139–151.Dunker, H.R. (1972) Structure of avian lungs. RespiratoryPhysiology, 14: 44–63.Flecknell, P.A. (1988) Laboratory Animal Anaesthesia.London: Academic Press.Green, C.J. (1975) Neuroleptic drug combinations in theanaesthetic management of small laboratory animals.Laboratory Animals 9: 161–178.Green, C.J. (1979) Animal Anaesthesia. London:Laboratory AnimalsGreen, C.J., Knight, J., Precious, S. and Simpkin, S. (1981)Ketamine alone and combined with diazepam orxylazine in laboratory animals. London: LaboratoryAnimals LtdHarthoorn, A.M. (1971) Chemical Capture of Animals.London: Baillière Tindall.Mero, M., Vainionpaa, S., Vasensius, J., Vihkonen, K. andRockkanen, P. (1989) Medetomidine-ketaminediazepamanaesthesia in the rabbit. Acta VeterinariaScandinavica, 85 (Suppl): 135–137.Nevalainen, T., Pyhala, L., Hanna-Maija, V. et al.(1989) Evaluation of anaesthetic potency ofmedetomidine-ketamine combination in rats,

BIRDS, LABORATORY & WILD ANIMALS 479guinea pigs and rabbits. Acta Veterinaria Scandinavica85: 139–143.Orland F.J. and Orland, P.M. (1946) Pentobarbitalsodium anesthesia in the Syrian hamster. Journal of theAmerican Pharmaceutical Association 35: 263–265.Piiper, J. (1972) In: Bolis, L., Schmidt-Nielsen, K. andMaddrell, S.H.P. (eds) Comparative Physiology.Amsterdam: North Holland Veterinary MedicineReviews, ch. 3, p. 204.Piiper, J. and Scheid, P. (1973) Gas exchange inavian lungs: models and experimental evidence.In: Bolis, L., Schmidt-Nielsen, K. and Maddrell, S.H.P.(eds) Comparative Physiology. Amsterdam: NorthHolland Veterinary Medicine Reviews,pp. 616–618.Sedgewick, C.J. (1986) Anesthesia for rabbits. VeterinaryClinics of North America. Food Animal Practice2: 731–736.

Anaesthesia for obstetrics 18INTRODUCTIONThere is no one anaesthetic agent or technique that isideal for all parturient animals. In veterinary practicethe choice of anaesthetic methods and drugs is ofteninfluenced by whether the offspring are alive andwanted, unwanted,or dead due to obstetrical problems.In any case the choice must be such as toensure the safety of the mother and any living foetus(es),comfort of the mother during parturition orhysterotomy and convenience of the obstetrician/surgeon. To make a rational choice the anaesthetistmust be familiar with physiological alterationsinduced by pregnancy and labour, the pharmacologyof the agents used, and significance of obstetric complicationsnecessitating assisted delivery of the offspring.Most studies have been carried out in ewes,but physiological alterations are broadly comparablein other species of animal even if their magnitudediffers. The following brief account of changes in physiologyand in actions of drugs administered duringpregnancy and parturition is a summary of many publishedpapers and accounts in standard textbooksand should apply to all species of domestic animals.THE STATE OF PREGNACYPHYSIOLOGICAL AND ANATOMICALALTERATIONSPhysiological and anatomical alterations occur inmany organ systems during pregnancy and deliveryof the foetuses. Early in pregnancy changes aredue, at least in part, to metabolic demands of thefoetus(es), placenta and uterus, due largely toincreasing levels of progesterone and oestrogen.Later changes starting around mid-pregnancy areanatomical in nature and are caused by mechanicalpressure from the enlarging uterus.Circulatory changesCirculatory changes develop primarily to meetincreased metabolic demands of the mother andfoetus(es). Blood volume increases progressively,most of the added volume being accommodated inthe increased capacity of vessels in the uterus,mammary glands, renal, striated muscle and cutaneoustissues so that there is no evidence of circulatoryoverload in healthy pregnant animals.Increase in plasma volume is relatively greaterthan that of red cells, resulting in haemodilutionwith decreased haemoglobin content and haematocrit.The purpose of this increase in blood volumeis usually assumed to be twofold. First, it increasesplacental exchanges of respiratory gases, nutrientsand waste metabolites. Secondly, it acts as areserve if there is any abnormal maternal bloodloss at parturition so that increased autotransfusionof blood can occur from the involuting uterus.Cardiac output increases in pregnancy to a similardegree as blood volume and there is an additionalincrease in cardiac output during all stages oflabour. In 3rd stage labour it probably results from481

482 SPECIAL ANAESTHESIAblood being expelled from the involuting uterusinto the general circulation. Peripheral vascularresistance usually decreases during pregnancy sothat ABP does not change. A serious decreasein venous return due to compression of the venacava and aorta by the enlarged uterus and itscontents can occur if the animal is restrained orpositioned in the supine position This decreasein venous return will, of course, cause a fall incardiac output for the heart cannot pump moreblood than is being returned to it. Cardiac workis increased during pregnancy so that at parturitioncardiac reserve is reduced and pulmonarycongestion and heart failure may occur in animalsthat had previously well compensated cardiacdisease.Respiratory system changesDuring pregnancy the sensitivity of the respiratorycentre to carbon dioxide is increased, presumablydue to changes in hormone levels, so that PaCO 2and serum bicarbonate decrease although arterialpH is maintained due to long term renal compensation.Oxygen consumption is increased by thedemands of the developing foetus(es), placenta,uterine muscle and mammary glands. Duringlabour, ventilation may be further increased byapprehension or anxiety. Airway conductance isincreased and total pulmonary resistance isdecreased, apparently from hormone-inducedrelaxation of bronchial smooth muscle. Cranialdisplacement of the diaphragm results fromincreasing volume of the gravid uterus leading to adecrease in FRC, so that it is possible for airwayclosure to occur at end-expiration. Reduction inoxygen storage capacity from reduced FRC leadsto an unusually rapid decline in PaO 2 duringapnoea. Some compensation for the tendency ofthe FRC to decrease is achieved by increases in thetransverse and antero-posterior diameters of thechest cavity and flaring of the ribs.Other systemsLiver function is generally well maintained duringpregnancy. Plasma protein concentration is decreasedbut total plasma protein is increased dueto increase in blood volume.Renal plasma flow (RPF) and glomerular filtrationrate (GFR) increase progressively, parallelingthe increases in blood volume and cardiac output.Due to increases in renal clearances blood urea andcreatinine levels are lower than in non-pregnantanimals.Uterine blood flow is directly proportional toperfusion pressure and inversely proportional touterine vascular resistance, so that it can be compromizedfrom vasoconstriction due to catecholaminerelease from fright or anxiety.PHARMACOLOGY OF DRUGSADMINISTERED DURING PREGNANCYThe effects of pregnancy on drug disposition, biotransformationand excretion are largely unknownin domestic animals. The MAC of inhalationagents is decreased due to unknown mechanisms.The increase in RBF and GFR favours renal excretionof drugs. Any drug administered to the motheris liable to cross the placenta to the foetus(es) andinduce effects similar to those observed in themother.Placental transfer of drugs is governed by thephysiochemical properties of the drug andanatomical features of the placenta. Transfer ofdrugs can occur by simple diffusion, facilitateddiffusion via transport systems, active transportand pinocytosis. Of these simple diffusion is by farthe most important and this will be affected by thesurface area and thickness of the placenta. Thelarger farm animals have thick epitheliochorialplacentae with relatively small areas for diffusiondue to their cotyledonary or patchy diffuse distribution,whereas dogs and cats have thinnerendotheliochorial placenta with larger zonularareas of implantation. Thus, the placental diffusionbarrier is greatest in ruminants, pigs andhorses and least in dogs and cats. However, thediffusion barrier does not appear to be of greatclinical significance in the transfer of drugs frommother to foetus(es) in any species of animal.More important is the diffusion constant whichis unique to each drug and determined by molecularweight, degree of protein binding in maternalblood, lipid solubility and degree of ionization inthe plasma. Most drugs used in anaesthesia have

OBSTETRICS 483large diffusion constants – low molecular weights,high lipid solubility and poor ionization – and diffuserapidly across the placenta. The exceptionsare the neuromuscular blocking drugs, which arehighly ionized and of low lipid solubility.Maternal blood concentrations of drug dependon total dose administered, site or route of administration,rate of distribution and uptake of it bymaternal tissues and maternal detoxification andexcretion. Thus drugs with rapidly declining plasmaconcentration after administration of a fixeddose (e.g. thiopental) result in a short exposure ofthe placenta and hence foetus(es) to high maternalconcentrations, whereas drugs administered continuously(e.g. inhalation anaesthetics, infusedagents during TIVA) are associated with a continuousplacental transfer to the foetus(es).The concentration of drug in the umbilicalvein of a foetus is not that to which the foetaltarget organs such as the heart and brain areexposed, for most of the umbilical blood passesinitially through the liver, where the drug may bemetabolized or sequestrated. The remainder ofthe umbilical blood passes through the ductusvenous to the vena cava where it is diluted bydrug-free blood from the hind end of the foetus.Thus, the foetal circulation protects vital tissuesand organs from exposure to sudden high drugconcentrations.CLINICAL SIGNIFICANCE OF CHANGESDURING PREGNANCY AND PARTURITIONCirculatory changes of pregnancy and parturitioncan put a mother suffering from even normallywell compensated heart disease at risk unless careis taken to ensure a minimum cardiac depressionfrom anaesthetic drugs. Ecbolics used early on inlabour can have an adverse effect on cardiovascularfunction. Oxytocin will induce vasodilatationand hypotension that will have an adverse effecton both mother and foetus(es) due to decreasedtissue and placental perfusion. Ergometrine causesvasoconstriction and may give rise to an increasein systemic vascular resistance sufficient to produceheart failure in the immediate postpartumperiod when cardiac output is high from theincreased circulating blood volume. Venousengorgement of the epidural space decreases thevolume of solutions needed to produce block toany given level.Reduction in FRC means that any respiratorydepression caused by drugs is more significant inpregnant than in non-pregnant animals andhypoventilation will lead to hypercapnia andhypoxaemia; the hypoxaemia is particularly undesirableduring labour when oxygen consumptionis increased. In small animals induction of anaesthesiawith inhalational agents will be more rapidthan in non-pregnant animals due to decrease inFRC and increased alveolar ventilation as well asthe decrease in MAC, but in recumbent large animalsshunting of pulmonary blood may make theinduction and maintenance of inhalation anaesthesiamore difficult.In monogastric animals there is an increasedrisk of both vomiting and silent aspiration of gastriccontents in parturient animals for frequentlythe time of last feeding is unknown, and intragastricpressure is increased in the stomach displacedby the gravid uterus. Risk of regurgitation of ruminalcontents when general anaesthesia isinduced seems to be great in cattle, but perhapsnot in sheep and goats which normally have lessfluid rumen contents.DRUG ACTIONSOpioidsOpioids rapidly cross the placenta from mother tofoetus(es) and can cause marked respiratory andcentral nervous depression in neonate(s) withsleepiness and reluctance to feed. Opioid antagonistsalso readily cross the placenta and it hasbeen suggested that they should be given to themother immediately before delivery to counterneonatal respiratory and central nervous depression,but this deprives the mother of analgesia atthe time when it is most needed and may result inher regaining consciousness on the operatingtable. If used, the opioid antagonists such as naloxoneshould be given to the neonate(s). Because theaction of naloxone is shorter than that of some opioids,depression may return when naloxone ismetabolized and careful observation is indicatedto allow this to be detected and treated by theinjection of more naloxone.

484 SPECIAL ANAESTHESIAα 2 adrenoceptor agonists;ketamineAll α 2 adrenoceptor agonists rapidly cross the placentaand can cause respiratory and cardiovasculardepression in both mother and babies,although this can be counteracted by antagonists.The use of acepromazine/ketamine combinationsis theoretically unwise but, in practice, providedonly minimal doses are used little harm appears toresult.Intravenous anaesthetics;neuromuscularblockersLow doses of thiopental, methohexital, propofoland Saffan produce minimal respiratory or centralnervous depression in neonates. Neuromuscularblocking drugs do not cross the placenta but areseldom needed in obstetrical anaesthesia. No musclerelaxation is required for vaginal delivery andin caesarian section the only time it might be neededis for suture of the abdominal wall, but this isusually very relaxed following removal of thebulky uterine contents. Use of neuromuscularblockers to decrease the quantity of more depressantanaesthetic agents needed is, however, a legitimateindication for their use in balancedanaesthesia techniques.Inhalation anaestheticsInhalation anaesthetics readily cross the placentalbarrier with rapid equilibration between themother and foetus(es). The degree of depressionthey cause in the neonate is directly proportionalto the depth of unconsciousness induced in themother. Deep levels of maternal depression willcause maternal hypotension, decreased uterineblood flow and foetal acidosis. There is a reductionin anaesthetic requirements with a fall in MAC.When measured in ewes, MAC is 25 to 40% lowerin gravid as compared with non-pregnant animals.Use of the less soluble agents enflurane, isoflurane,sevoflurane and desflurane will lead to more rapidrecovery of the newly delivered animals thanwhen more soluble agents such as halothane areemployed. Nitrous oxide will often enable concentrationof more potent soluble anaesthetic agent tobe reduced and its use does not add to depressionof the newborn.Foetal haemoglobin can carry more O 2 for agiven PO 2 due to the low concentration of 2,3-diphosphoglycerate (2,3-DPG) in foetal red cells.This ensures a higher level of haemoglobin saturationat the normally low PO 2 of umbilical venousblood. Administration of O 2 to the mother resultsin a most significant increase in foetal oxygenationand maternal inspired O 2 concentrations of over50% during general anaesthesia are associatedwith delivery of more vigorous newborn. However,it must be remembered that administration ofhigh concentrations of oxygen for any prolongedtime to spontaneously breathing animals may leadto unrecognized, but fatal, hypercapnia.Local analgesicsLocal analgesics are not as harmless as sometimessupposed. Amide derivatives (e.g. lignocaine,mepivacaine, bupivacaine) are broken down byhepatic microsomal enzymes. After absorptionfrom the site of injection maternal blood levelsdecrease slowly and blood levels can reach a significantlevel in the foetus(es) causing depressionin the neonate. Sufficiently high concentrationsseldom occur after epidural or paravertebraladministration, but can be found after the indiscriminatelocal infiltration of large volumes oflocal analgesic solutions. Epidural block may producehypotension and this may be treated byinfusing fluid to fill the dilated vascular bed, orbetter, by injection of ephedrine. Ephedrine actscentrally to increase venous tone and thus cardiacpreload; it has minimal vasoconstrictor effect onthe arterial system.AnticholinergicsBecause glycopyrrolate does not readily cross theplacental barrier it is probably the anticholinergicof choice if anticholinergics are to be used to minimizethe effects of traction on the uterus andbroad ligaments by the surgeon.HORSESIn horses, obstructed labour quickly leads toexhaustion of the mare and death of the foal.

OBSTETRICS 485Prompt relief is necessary and anaesthesia mayhave to be provided for vaginal delivery or caesariansection. The viability of the foal will depend onits state at the time of anaesthesia but the mare willinvariably have a distended abdomen and mayshow signs of weakness or be in shock. The anaestheticproblems presented by the mare are verysimilar to those encountered in horses with bowelobstruction, although the degree of dehydration isgenerally much less severe. When the foal is alive,the effects of any drugs to be given to the mare onuterine blood flow and foetal oxygenation, as wellas on the respiratory centre of the foal after delivery,must also be taken into account.It can be assumed that any drug given to themare will cross the placenta to the foal, but its actualconcentration in the foal will depend on suchfactors as fat solubility, degree of protein bindingand ionization, dose given to the mare and timeinterval between its administration and deliveryof the foal, and the neonatal foal’s ability to eliminatethe drug from its body. Thus, opioids such aspethidine given to the mare will produce respiratorydepression in the foal, but low doses of thiobarbiturateswill be tolerated because recoveryfrom central nervous depression is more dependenton redistribution than on metabolism. Themore insoluble inhalation anaesthetics given to themare are readily excreted by the foal if it breathesproperly after delivery. Although neuromuscularblocking drugs such as vecuronium, atracuriumand pancuronium do not cross the placenta in significantamounts guaiphenesin does, so for obstetricalanaesthesia it is best avoided or used in muchreduced dose if the foal is alive when anaesthesiais induced. Respiratory and central nervousdepression in the foal resulting from administrationof opioids to the mare can be antagonized bygiving naloxone to the foal but, in general, stimulantdrugs have only a minor role in the managementof problems in newborns. Doxapram(0.5mg/kg i.v.) may be effective in provoking thefirst breath and aiding lung expansion. However,instead of relying on stimulant drugs to resuscitatefoals, resuscitation should normally involve clearingof the airway, endotracheal intubation, O 2administration, and IPPV.Abdominal distension of the mare will probablybe the problem which gives rise to most concernbecause many mares have great difficulty inbreathing once they are recumbent under generalanaesthesia. Due to intrapulmonary shunting ofblood they may also be difficult to keep unconsciouswith inhalation anaesthetics. In the supineposition which some surgeons prefer for caesariansection, the weight of the gravid uterus will compressthe vena cava and aorta, reducing venousreturn and causing a marked decrease in ABP.Once the foal is delivered, the condition of themare shows immediate improvement – pulmonaryventilation increases and ABP risestowards normal levels. Attempts by the surgeon toremove the placenta should be discouraged sincethis provokes hypotension and, occasionally, considerableblood loss requiring the infusion of 20 to30 ml/kg of lactated or acetated Ringer’s solution.To minimize difficulties before delivery of the foal,the mare should be positioned so that she is lyinginclined towards her left side and respiration mayneed to be controlled. As always in equine anaesthesia,the magnitude of the problems encounteredis related to size; small pony mares presentonly relatively minor problems. It is important toremember this for techniques successful for electivecaesarian section in small experimental ponymares operated on in lateral decubitus are ofteninadequate for the large mares of the heavy breedsrequiring emergency obstetric procedures while inthe supine position.In practice, vaginal repositioning and deliveryof the foal can often be carried out in the sedatedmare, using one of the drug combinations discussedearlier in this book. If general anaesthesia isessential the α 2 adrenoceptor agonist/ketaminecombination, in spite of some theoretical objections,can be recommended, for it has been usedwithout giving rise to problems in either theparturient mare or the foal. Should longer periodsof light general anaesthesia be required small i.v.doses of thiopental (or after delivery of the foal,guaiphenesin), may be given to prolong the effectsof this drug combination.Caudal epidural block is not as useful as it is incattle because in mares there is a rather long delaybetween injection and onset of full analgesia. A450kg mare requires 6 to 8 ml of 2% lignocaine or2% mepivacaine (or 0.17 mg/kg xylazine or 60µg/kg detomidine diluted in 10 ml of 0.9% NaCl)

486 SPECIAL ANAESTHESIAfor effective analgesia whilst remaining standingwith no apparent side effects. The development ofmaximum analgesia can be delayed for 10 to30minutes.For caesarean section, if the foal is alive, inductionwith an α 2 adrenoceptor agonist before i.v.thiopental or methohexital followed by endotrachealhalothane/oxygen or isoflurane/oxygenseems to be quite satisfactory, but ketamine isundoubtedly better than either of the barbituratesas the induction agent. Only the minimal amountsof halothane or isoflurane should be used andIPPV may be necessary until the foal is delivered.Involution of the uterus is hastened when xylazinehas been used and may be assisted by 2.5 to10 units i.v. of oxytocin. Bleeding from the uterus isbest controlled by i.v. injections of 3 to 5 mg ofergometrine tartrate, but this may give rise to cardiacarrhythmias in hypercapnic or hypertensiveanimals. Vigorous supportive therapy with i.v.fluids may be necessary. If the foal is dead anytechnique of general anaesthesia suitable forlaparotomy in horses may be used.CATTLEIn cattle, caudal block is nearly always used forvaginal delivery of the calf. The substitution ofxylazine for lignocaine (0.05 mg/kg xylazine in10 ml 0.9% saline for 5 to 10 ml 2% lignocaine)confers no obvious advantages. Whenever possiblesedation should be avoided but, if needed forcontrol, xylazine (0.05 mg/kg i.v.) will, in mostcases, provide adequate maternal tranquillizationto enable the block and obstetricalmanoeuvres to be undertaken with minimaltrouble. Lumbar segmental epidural block maybe used for caesarian section carried out throughthe left flank of the standing animal but it is noteasily performed and most veterinarians preferto use paravertebral block of the 13th thoracic,1st, 2nd and 3rd lumbar nerves on that side.Local infiltration techniques can be employedbut they do not relax the abdominal muscles and,if the foetus is alive, the injection of large volumesof the amide-type local analgesics mayresult in cardiopulmonary depression in theneonatal calf.Caesarian section via a ventral abdominal incisionis usually carried out under general anaesthesiawith endotracheal intubation. Anaesthesia maybe induced by the i.v. injection of minimal doses ofxylazine (0.1 mg/kg)/ketamine (2.2 mg/kg), thiopentone(5–10 mg/kg), or even propofol (0.2 mg/kg) and, after endotracheal intubation maintainedwith an inhalation agent (usually halothane orisoflurane). Alternatively, after xylazine (0.1 to 0.15mg/kg i.v.) or detomidine (10 to 20 µg/kg i.v.) hasbeen given to produce deep sedation, the animalmay be intubated and anaesthesia completed bythe administration of the inhalation agent.Involution of the uterus after delivery may beassisted by the use of ecbolic drugs provided thecow is not hypercapnic or hypertensive. All cowssubjected to caesarian section under generalanaesthesia should be given calcium borogluconates.c. to prevent the occurrence of hypocalcaemiawhich is otherwise frequently seen in thepostoperative period. Postoperative analgesia isalso important and 0.5 to 1.0 g pethidine (meperidine)depending on the size of the cow, repeated at4 to 6 hourly intervals for the first 24 hours, hasproved to provide analgesia as shown by the cowlooking comfortable and cudding or eating.Removal of a dead, putrefying normal-sizedcalf by hysterotomy should only be attemptedafter resuscitation of the toxaemic or shocked cowwith intravenous fluids; antimicrobial cover isessential and the cow should be closely observedfor adverse reactions to the antimicrobial drugused.SHEEP AND GOATSSheep are seldom given any analgesia or anaesthesiafor the vaginal delivery of lambs but, in difficultcases requiring extensive repositioning of thelamb in the birth canal, caudal block is verysatisfactory, using 1 ml/4.5 kg of 2 % lignocainehydrochloride. For caesarian section, which isusually carried out through the left flank, epiduralor paravertebral blocks, local infiltration andgeneral anaesthesia are all suitable. Sedation,when indicated by the behaviour of the ewe, maybe obtained with i.v. diazepam (0.25 to 1.0 mg/kg).The ewe is usually easily restrained for operation

OBSTETRICS 487and hence techniques of local analgesia arepopular. Probably the technique of choice isparavertebral block of the 13th thoracic, 1st, 2ndand 3rd lumbar nerves, for the ewe is then able tostand and suckle her lambs immediately the operationis completed and the wound area remainsanalgesic for one or more hours depending on thelocal analgesic drug used. If local infiltration isused care must be taken to restrict the total dose ofany amide-type local analgesic to below 5 mg/kgto minimize toxicity in the ewe and the likelihoodof depression of the lambs.Ewes carrying dead lambs or suffering frompregnancy toxaemia are often very toxic, dehydratedand dull or collapsed. Hysterotomy shouldbe preceded by resuscitation with intravenousfluids.Postoperative analgesia is all too often neglected.The ewe, like any other animal, is entitledto adequate pain relief in the postoperative periodand 4 hourly morphine (up to 10mg i.m.), pethidine(meperidine) up to 250 mg i.m., or epidural opioiddrugs should be used as freely as may be requiredto keep the animal comfortable. Obviously,epidural block will have minimal effects on thesuckling lambs.Goats do not seem to be as robust as sheep,require more careful handling and have a greaterneed for effective postoperative analgesia toensure rapid recovery from operation. Postoperativeanalgesia can be obtained with doses ofmorphine and pethidine (meperidine), butorphanolor buprenorphine as used in sheep.Many individual goats are much more used tohuman company than are sheep and seem toderive comfort from the presence of sympatheticpeople.PIGSAnaesthesia for obstetrical procedures in sows isalmost completely limited to provision of anaesthesiafor caesarean section. The general principlesare similar to those in all other species of animal –it is necessary to provide adequate surgical conditionsto prevent the sow from experiencing painand to use a method which produces minimaldepression of the piglets. Ideally, both the sow andpiglets should recover from the effects of theanaesthetic in the minimum of time.Caesarian section may be carried out underconditions which vary from those encountered onthe farm to those provided in an operating theatre.Elective caesarian section is carried out more commonlyfor the production of minimal disease herdsof pigs, or gnotobiotic animals for research purposes,than in ordinary farm sows, but is usuallyperformed in well equipped operating theatres.On the farm, caesarean section is probably bestcarried out under local or regional analgesia.Although paravertebral blocks are theoreticallypossible, they are difficult to perform because thethick layer of subcutaneous fat makes palpation oflandmarks almost impossible, and infiltration ofthe line of incision is the method usuallyemployed. Epidural block may also be used (seelater).The major problem is the restraint of the sowand today sedation with azaperone is usually usedfor this although the drug does cross the placentalbarrier and the piglets are sleepy when delivered.However, respiratory depression in the offspringseems minimal and if kept warm they usually survive.The sedative effects of azaperone on the soware rather prolonged and she may not be able tosuckle the piglets for some hours; if left unattendedwith the neonatal piglets she may suffocatesome by lying on them. If the sedation producedby azaperone is inadequate, i.v. thiopental or metomidatemay be given to effect. This does notappear to add to the depression of the piglets andis preferable to increasing the dose of azaperone. Ifthiopental or metomidate is used the sow losescontrol of her airway, so that care must be taken toensure that respiratory obstruction does not develop.In most animals it is as well to limit the totaldose of the i.v. agent to that which just producesimmobility and to supplement with some form oflocal analgesia.Under conditions encountered in hospitals,techniques are not usually limited by availabilityand a wide variety of techniques can be employed.The piglets are not always returned to the dam andin these circumstances speed of recovery of thesow is less important than under farm conditions.Surgical sterility is usually vital and the main taskof the anaesthetist is to ensure unconsciousness

488 SPECIAL ANAESTHESIAand immobility so that asepsis is not broken bymovement of the sow during the operation. Thestaff and equipment needed for resuscitation of thepiglets are usually available but in elective caesariansections there is always the risk of the deliveryof premature young and the resuscitation of theseis not always easy.Probably the most viable piglets are obtainedwhen anaesthesia is induced and maintained withan inhalation anaesthetic and maintained with ahigh concentration of inspired oxygen. In themajority of sows anaesthesia is rapidly attainedwith agents such as halothane, isoflurane or enflurane,but if the sow is very large or difficult to handle,a minimal dose of thiopental or propofol canbe employed.Satisfactory results are also achieved by theuse of ketamine, usually in combination withdiazepam (2 mg/kg i.v.) and atropine (0.03 mg/kgi.v.) followed by i.v. injection of ketaminegiven to effect. Usually about 5 to 10 mg/kg ofketamine is needed to produce a peculiar state inwhich the sow appears to be aware of the environmentyet does not react to skin incision orother surgical stimulation. If necessary nitrousoxide with or without a more potent inhalationanaesthetic can be used to control any slight restlessnesswhich may occur towards the end of theoperation.Sedative premedication with azaperone followedby induction of anaesthesia with inhalationor intravenous agents (such as medetomidate) hasbeen widely used for elective caesarean sectionwith generally satisfactory results. However, in theauthors’ experience, there can be no doubt thatpiglets delivered after the use of this sedative drugare, for some hours, sleepier than if no sedation isemployed.Methods of anaesthesia involving the use ofneuromuscular blocking agents result in the deliveryof lively piglets and rapid recovery of the sow;they can be used whenever endotracheal intubationand IPPV can be carried out. However, it isessential to ensure that the sow is completelyunconscious and it is sometimes difficult to be sureof this without having to administer large doses ofanaesthetic or other drugs which will give rise tomarked respiratory and central nervous depressionin the piglets. Techniques of this nature are,therefore, best avoided except by the experiencedveterinary anaesthetist.Involution of the uterus after delivery of thepiglets may, if the animal is not hypoxic or hypercapnic,be helped by i.v. 2–10 i.u. oxytocin or, ifbleeding is a problem i.v. 1.0–1.5 mg ergometrinetartrate, but this latter drug may produce cardiacarrhythmias if the PaCO 2 is elevated when it isgiven.DOGSFor elective caesarian section to deliver live pups itis essential that the minimum of depressant drugsshould be in the pups by the time of their delivery,and that the bitch shall be conscious as soon aspossible after operation so that she will accept andbe able to look after her offspring. It is also necessary,however, that the bitch shall not appreciatepain during the operation, that the surgeon shallbe provided with adequate operating conditionsand the bitch with adequate postoperative analgesia.Although there were several studies publishedprior to 1975 (Wright, 1939; Freak, 1962; Mitchell,1966; Goodger & Levy, 1973) there have been manynew agents introduced since then and there is atremendous variation in perioperative management.The problems presented and the generalprinciples of management, however, have notchanged since the earlier days.The bitch may be fit and healthy at the time ofoperation (as she should be for an elective operation)or she may be exhausted from a prolongedobstructed labour. Even after several hours of starvationher stomach may not be empty and if shehas already delivered one or more puppies spontaneouslyper vaginum she may have voluntarilyingested placental material. Thus the likelihood ofvomiting at induction of general anaesthesia mustbe recognized as a potential hazard. Premedicationwith a low dose of morphine (0.1 mg/kg) orpapaveretum (‘Omnopon’ 0.2 mg/kg) will usuallyprovoke vomiting and ensure an empty stomachbut may cause some depression in the pups.However, as long as low doses are used this willseldom be a problem and in any case, if it occurs itmay be overcome by giving the pups naloxone.There is little quantitative information regarding

OBSTETRICS 489the dose of naloxone which may be needed but as.c. dose of 0.04 mg/kg is suggested as being anappropriate initial dose. Similarly, the use ofxylazine or medetomidine for their emetic propertiesmay cause prolonged and serious respiratorydepression in the offspring but this can be overcomeby the use of atipamezole (up to 10 µg/kgs.c.). Sleepiness of the pups caused by premedicationof the bitch with acepromazine cannot, however,be counteracted for there is no specificantagonist to the phenothiazine derivatives.In the supine animal pressure on the caudalvena cava from the gravid uterus causes circulatorydisturbances; pressure on the posterior venacava can interfere with venous return to the heartand result in arterial hypotension. This pressurecan be avoided by a wedge of plastic foam materialplaced under the right side of the supine bitch.Major circulatory changes also occur once intraabdominalpressure has been reduced by removalof the gravid uterus or the pups and the ability ofthe bitch to compensate for these disturbancesmay have been reduced by the drugs used for generalanaesthesia or the sympathetic blockadeinduced by some techniques of local analgesia. Itis, therefore, advisable to set up an intravenousinfusion prior to the induction of anaesthesia andthis may be essential if the bitch is already toxic orvery exhausted. Respiratory function usuallyimproves greatly after delivery of the puppies andthe concentration of any inhalation anaestheticbeing administered at this time may need to bereduced if overdose is to be avoided.Some of the agents used during anaesthesiamay interfere with the involution of the uterus. Inwomen, halothane is particularly likely to lead topostoperative uterine haemorrhage after caesareansection but the difference in placental attachmentmakes this complication much less likely inbitches. Provided the bitch is not hypercapnic ani.v. ecbolic such as oxytocin (2–10 IU), orergometrine (up to 0.5 mg) depending on the sizeof the bitch, may be given after delivery of thepups to promote involution of the uterus and controlany uterine haemorrhage.Although there are considerable differences inthe rate at which drugs cross the placenta, it isalways safest to assume that any drug given to thebitch will exert an influence on the pups in thepostdelivery period. As long as the respiratorydepression is not too severe the pups will rapidlyeliminate any of the less soluble inhalation agentswhich may have come to them from the motherbut elimination of parenterally administeredanaesthetic agents may be much more difficult dueto the immaturity of the newborn pups’ detoxicatingmechanisms. For example, it has been estimatedthat renal function may take as long as 1 to 2weeks before reaching adult levels (Baggot, 1992).Anaesthetic-induced depression of the offspringcan be avoided by the use of local analgesia.Epidural block is particularly suited to caesareansection but it should only be used in quiet, easilyrestrained bitches. If heavy sedation is requiredfor the restraint of the animal the pups willbe affected and the method will offer no -advantages over a well managed generalanaesthetic.In bitches of reasonable temperament, premedicationbefore general anaesthesia may be limitedto an anticholinergic agent, but minimal doses ofopiates may be used and if they cause vomiting thestomach should be empty when anaesthesia isinduced.Induction of general anaesthesia with aninhalation agent has the advantage of rapid eliminationby the puppies and, when carried out by anexperienced anaesthetist, can be both rapid andexcitement-free. The main disadvantage of inhalationinduction is that vomiting may occur beforeendotracheal intubation is possible, so suctionapparatus should be available to enable the airwayto be cleared rapidly if the bitch is unable to do soby coughing. Halothane, enflurane, isoflurane,sevoflurane and desflurane can all be used for caesariansection with satisfactory results but (thenow obsolete) methoxyflurane usually producedmarked depression of the pups for some time aftertheir delivery.In large or bad tempered bitches an intravenousagent may be used for induction of anaesthesia.Propofol in doses of 4 to 6 mg/kg is probably theagent of choice but methohexital (up to 2.5 mg/kg)and thiopental (up to 5 mg/kg) can be used withoutrisk of serious depression of the pups. If endotrachealintubation is not possible at these lowdosages anaesthesia may be deepened with aninhalation anaesthetic administered by facemask.

490 SPECIAL ANAESTHESIAWhen i.v. agents have been used it is advisable towait a few minutes (about 15 minutes whenpropofol is used) before delivering the pups inorder to allow blood levels of induction agent todecline. Dodman (1979) when reviewing the literatureon the subject, pointed out that after a barbiturateinduction of anaesthesia there is oftensufficient barbiturate remaining to cause considerabledepression in the bitch at the time of deliveryof the pups, yet the pups are surprisingly lively.Accumulation of the barbiturate in the foetal liver,as shown by Finster et al. (1972) or further dilutionof the drug before it reaches the foetal brain mayexplain this. A recent review, together with survivalrates for the bitches was published by Moonet al. (1998).Techniques involving the use of neuromuscularblocking agents can be used very satisfactorily forcaesarian section, as these drugs do not cross theplacenta in sufficient quantities to paralyse themuscles of the offspring. However, there is apparentlyno real advantage to be gained from the useof neuromuscular blockers.Where apparatus for the administration ofinhalation anaesthesia is not available, seriousconsideration should be given to the use of lightsedation together with some method of local analgesiasuch as epidural block or local infiltration ofthe line of incision and topical application of localanalgesic to the broad ligaments.Postoperative pain relief for the bitch is essentialbut care must be taken to ensure that drugsused for this purpose are not excreted in the milkin concentrations which may affect suckling pups.The provision of adequate pain relief may poseproblems when opioid antagonists have been usedto produce more rapid awakening of the bitch.CATSThe requirements of anaesthesia for caesarian sectionin the cat, and the problems likely to beencountered, are similar to those already discussedabove for dogs. Although cats may vomiton induction of anaesthesia, inhalation of vomit isless likely than in bitches for cats have more activelaryngeal reflexes. Nevertheless, endotrachealintubation should be carried out as soon as anaesthesiais induced and, when a non-cuffed tube isused, a pharyngeal pack introduced around thetube.Many cats presented for caesarian section orhysterectomy are carrying dead kittens and theuterus may be infected. Ideally, in such cases a balancedelectrolye solution should be infused beforeanaesthesia is induced but, unless the queen isexhausted or otherwise very ill, this is oftendelayed until after careful anaesthetic induction.Premedication before caesarian section is usuallylimited to the administration of anticholinergics,and an inhalation induction of anaesthesiawith low-solubility agents leads to the quickestrecovery of both mother and kittens. With care,such an induction can be smooth, but many anaesthetistsprefer to induce unconsciousness withsmall doses of thiopental, methohexital, propofolor Saffan before going on to the inhalation anaesthetic.Only minimal quantities of any intravenousagent should be used and inhalation agents shouldbe employed to maintain the lightest possible levelsof anaesthesia.If total i.v. anaesthesia has to be used for caesariansection, Saffan is probably the best available.Although the Saffan steroids cross the placentalbarrier and will affect the kittens, no noticeablerespiratory depression results. If it is necessary touse Saffan alone for this operation it is probablethat it should be used in conjunction with localanalgesia so that the lightest levels of generalanaesthesia can be employed.Diazepam or midazolam with ketamine(

OBSTETRICS 491condition will be no better than after well-administeredgeneral anaesthesia.Maternal postoperative analgesia may be providedby the use of small doses of morphine(0.05 mg/kg i.m.), i.m. pethidine (meperidine)10mg/kg, or butorphanol (0.2 mg/kg). Any sucklingkittens must be carefully watched for signs ofundue sleepiness that indicate high drug levels inthe mother’s milk.REFERENCESBaggot, J.D. (1992) Drug therapy in the neonatal animal.In: Principles of Drug Disposition in Domestic Animals:the Basis of Veterinary Clinical Pharmacology.Philadelphia: W.B. Saunders.Dodman, N.H. (1979) Anaesthesia for caesarian sectionin the dog and cat: a revision. Journal of Small AnimalPractice 20: 449–460.Finster, M., Morishima, H.O., Mark, L.C., Perel, J.M,Dayton, P.G. and James, L.S. (1972) Thiopentalconcentrations in the fetus and newborn.Anesthesiology 36: 155–158.Freak, M.J. (1962) Abnormal conditions associated withpregnancy and parturition in the bitch. VeterinaryRecord 74: 1323–1325.Goodger, W.J. and Levy, W. (1973) Anaestheticmanagement of caesarean section. VeterinaryClinics of North America: Small Animal Practice3: 85–99.Mitchell, B. (1966) Anaesthesia for caesarean sectionand factors influencing mortality rates of bitchesand puppies. Veterinary Record 79: 252–257.Moon, P.F., Erb, H.N., Ludders, J.W., Gleed, R.D. andPascoe, P.J. (1998) Perioperative management andmortality rates of dogs undergoing cesariansection in the United States and Canada. Journalof the American Veterinary Medical Association213: 365–369.Wright, J.G. (1939) Caesarian hysterotomyhysterectomy.Veterinary Record 51: 1331–1346.

Intrathoracic surgery 19INTRODUCTIONThe anaesthetic management of the pneumothoraxcreated by the wide opening of the chestwall and/or diaphragm for surgical access to thecontents of the thoracic cavity involves ‘controlledrespiration’ or ‘IPPV’ (Chapter 8). Although inveterinary practice ventilation of the lungs bymanual squeezing of the reservoir bag of theanaesthetic breathing circuit is still carried outin centres where little intrathoracic surgery isundertaken, or where neuromuscular blockingdrugs are seldom used, the use of mechanicalventilators is now widespread. Surgeons find iteasier to work with the regular movementproduced by these devices and their use makesit possible to stabilize the tidal and minute volumesof respiration, the airway pressures and the durationof the inspiratory and expiratory periods, in a waywhich cannot be achieved by manual ‘bag squeezing’.Apart from the fact that IPPV is obligatorywhile the pleural cavity is open to the atmosphere,the actual anaesthetic methods employed forintrathoracic surgery are largely governed by thepersonal preferences and experience of the anaesthetist.The main anaesthetic problems centrearound the elimination of any pneumothoraxremaining after closure of the thoracotomy incisionand here the close cooperation between thesurgeon and anaesthetist is essential for their satisfactoryresolution.CLOSURE OF THE CHESTThe anaesthetic technique used while the chest isbeing closed varies with the nature of the operationbut should always include drainage of thepleural cavity. In the past, after a limited operationnot involving injury to the lung the chest was oftenclosed without drainage. An attempt was made toachieve full re-expansion of any collapsed area ofthe lung tissue and to maintain full control of thebreathing with the lungs held in full expansion asthe last suture was tied to make the chest airtight.Sometimes a cannula was left in the pleural cavityuntil the thoracotomy wound was completelyclosed and this cannula was withdrawn quicklywhile the lungs were held in what was presumedto be full expansion. However, the methodsemployed never succeeded in removing all theresidual air from the pleural cavity, portions of thelung remained collapsed and often became a focusof infection. The air trapped in the pleural cavitycaused movements of the chest wall to be transmittedto the lung by negative intrapleuralpressure and pleural exudation occurred as aresult of this.Proper drainage of the pleural cavity withremoval of all the residual air overcomes all ofthese problems but if, on occasion, the chest has tobe closed without drainage the amount of airtrapped in the pleural cavity can be minimized byinserting a catheter through an intercostal space493

494 SPECIAL ANAESTHESIAand applying suction after the chest wall is closed.The catheter is then pulled out with a sharp tug.Alternatively, when the thoracotomy wound hasbeen closed a large-bore catheter connected to asuction apparatus is introduced into the pleuralcavity and suction applied until there is a negativepressure present in the system. The catheter maybecome blocked by the lung and the method istherefore not very satisfactory. It is, however,commonly used in cats where, after closure of thethorax, a 13 swg intravenous catheter may beintroduced into the pleural cavity, the needle partbeing withdrawn after penetration of the skin andthe blunt ended catheter forced through the intercostalmuscles and parietal pleura.When there is any risk of injury to the lungwhich could cause a leak, or there is any likelihoodof continuing haemorrhage into the pleural cavitythe chest must be drained. Underwater drainage isundoubtedly the most reliable and informativeprocedure and for this the drain tube is connectedto a container of water or a weak aqueous solutionof chlorhexidine. The drain tube dips about 2.5 cmbelow the surface of the fluid and should have aninternal diameter of about 0.5 cm. The containermust have an internal diameter of not less than15cm. The system acts as a non-return valve andallows air or fluid to be expelled from the pleuralcavity but prevents the indrawing of air duringinspiration. When the closure of the chest is complete,inflation of the lung, or spontaneous respiratorymovements of the animal, forces air out of thepleural cavity whenever the pressure in the pleuralsac is greater than about 2.5 cmH 2 O (0.25 kPa),i.e. the depth which the tube dips below the surfaceof the water. Provided that the container iskept at least 80 cm below the level of the animal’sbody, water cannot be aspirated into the chest, forno effort of the animal can lift the water up this distance.The large diameter of the container shouldensure that no matter how high the level rises inthe tube the end of the tube will always be belowthe fluid surface (Fig. 19.1).When the animal breathes spontaneously thewater level in the drainage tube rises on inspiration(as the cavity between the lung and chestwall increases) and falls on expiration. When thelung occupies the whole of the pleural space thepressure does not show marked fluctuationsFor connectionto chest drainGlass or rigidplastic bottle2.5cm(1inch)Glass or stiff plastictubes of 0.5cm ID>15cm diameterFor connectionto suctionRemovablebungDilutechlorhexidineFIG.19.1 Underwater-seal drain bottle.The bottle,tubing and bung can be autoclaved before use or thewhole apparatus may be purchased,sterile and ready foruse from a commercial source.during the respiratory cycle. If, however, the lungis not fully expanded large variations of pressureoccur. Observation of the water level in the glass ortransparent plastic tube thus provides useful informationas to the state of expansion of thelungs – the greater the amplitude of the swing ofthe water level in the tube the poorer is the expansionof the lung. The drain should be allowed toremain in the pleural cavity until the lung is fullyexpanded as shown by minimal amplitude of theswing with a completely unobstructed drain. It isthen pulled out with a sharp tug during expiration,and a skin suture,which has been laidfor the purpose, tied tightly to occlude the hole inthe skin.After any operation which has involved strippingof the visceral layer of the pleura there will bean air leak from the raw surface of the lung. In suchcircumstances suction may have to be applied tothe far side of the underwater seal apparatus tocontrol the pneumothorax. This suction must bemaintained until there is no bubbling of air, indicatingthat the leak has been sealed off by inflammatoryreaction. It may not be possible to removethe drain for up to 48 hours after operation and

INTRATHORACIC SURGERY 495during this time the animal must be kept wellsedated. Experience has shown that in cats thissedation is best achieved by the use of Saffan giveneither as a continuous infusion or by intermittentinjection, while in dogs combinations of morphineand diazepam give excellent results particularlywhen combined with the instillation of 3 to5ml/10 kg of 0.25 % bupivacaine into the pleuralcavity. Whatever sedation and analgesia is used itis important that restlessness is overcome withoutat the same time producing respiratory depression.After any thoracotomy the animal must beexamined both physically and radiologically forevidence of lung collapse. Collapse of a lung, or ofa lobe of a lung, may necessitate immediate intrabronchialsuction to remove any material occludingthe bronchus to the lung or lobe. Wheneverpossible, an immediate postoperative chestradiograph should be taken to confirm full expansionof the lungs, the absence of pneumothoraxand the position of any drainage tubes. It alsoserves as a reference against which later films canbe assessed.The drain can be used in any animal and sterileunits ready for connection to the pleural catheterare commercially available. The outlet tube fromthe air above the surface of the liquid in the containercan be connected to a source of suction.Suction is usually only necessary when there is acontinuous air leak in the thoracic cavity but, if theleak is gross, the application of suction can be lifesaving.Suction must be provided from a high-volume,low-pressure apparatus.For horses, cattle, sheep, goats, pigs and ambulantlarge dogs it is sometimes more convenient touse a Heimlich valve (Fig. 19.2). These are alsoavailable from commercial sources. This valveshould be attached to the animal’s chest wall by askin suture and drain tubes tied tightly to the valveinlet – a Y-piece can be used if more than one drainis in use. The Heimlich valve gives no indication asto the state of expansion of the lungs and regular,frequent inspection is needed to check that it isworking properly.All drainage tubes introduced into the pleuralcavity should be of adequate bore and made fromsiliconized material which does not soften toomuch at body temperature. Small-bore chestdrains are almost worse than useless – they occludeFIG.19.2 Heimlich chest drain valve.easily if they become slightly kinked around a riband are readily blocked by the expanded lung or asmall blood clot. For cats a 2.5 mm internal boretube is the narrowest which should be used, buteven in the smallest of dogs and puppies 7.5 mmbore diameter tubing should be used. Commerciallyavailable, sterile chest drainage tubes aredesigned for use in man and may have more sideholes than the one or two convenient for use insmall animals.Dogs and cats can be turned from side to side topromote drainage of either air or blood but in largeanimals such as horses it is often necessary toinsert two chest drains – one ventrally for thedrainage of blood and one dorsally for thedrainage of air. These can be connected through aY-tube to a Heimlich drain (Fig. 19.3).The time for removal of the drain should be amatter for consultation between the surgeon and

496 SPECIAL ANAESTHESIADrain for air Y-connectorHeimlich drainsecured tochest wallFIG.19.3 Two chest drains for blood or fluid drainsconnected to a Heimlich valve by aY-piece connector fordrainage of both air and fluid from a standing horse.anaesthetist. It is essential that it should beremoved as soon as it is of no further use butshould a pleural effusion or pneumothorax developafter it has been taken out, another intercostaldrain should be introduced immediately underlocal infiltration analgesia.ANAESTHETIC MANAGEMENT FORSPECIFIC SURGICAL PROCEDURESSIMPLE THORACOTOMY FOR NON-PULMONARY LESIONSThoracotomies for most non-pulmonary lesionspresent few special problems. Large neoplasmswithin the thorax can cause an animal considerablerespiratory difficulty but removal of thespace-occupying lesions eases the respiration atonce. In removing some of the more extensivemediastinal tumours the surgeon may open bothpleural cavities but with the maintenance of controlledventilation no trouble is encountered duringoperation. Carcinomata of the bronchi mayrelease catecholamines when manipulated by thesurgeon. It may be necessary to drain both pleuralcavities and the two intercostal drains can be connectedto the same underwater seal or Heimlichdrain by a Y-connector.OESOPHAGEAL SURGERYThe problems in oesophageal surgery arise fromthe danger of regurgitation of food and/or salivawhich have been retained in the oesophagus.Prompt endotracheal intubation in the proneanimal with the head raised will usually preventthis mishap from occurring. Thoracotomy foroesophageal surgery presents no special anaestheticproblems that have not already beendiscussed.REPAIR OF RUPTURES OF THE DIAPHRAGMAlthough the majority of diaphragmatic rupturesare best repaired through an abdominal incisionthe pleural cavity is, of course, opened to theatmosphere during the course of the operation.The anaesthetic management of these cases is notalways easy.Diaphragmatic rupture produces respiratoryinefficiency which results both from reducedbreathing capacity and from an unbalanced distributionof blood and air within the lungs. The presenceof abdominal viscera and effusion within thechest reduces the vital capacity; the absence of displacementof effective diaphragmatic movementlimits the enlargement of the thoracic cavity.Twisting or displacement of the lung lobes causespartial obstruction of the bronchi, leading tothe uneven distribution of the inspired air. Theblood passing through overventilated areas ofthe lung will lose more CO 2 than it would undernormal conditions, but cannot become more thanfully oxygenated. In the under ventilated areas oflung both O 2 uptake and CO 2 elimination areimpaired. Because of these effects the mixed bloodreturning from the lungs to the systemic circulationusually has a PaCO 2 near to normal, but itsPaO 2 is low, i.e. the main threat to the animal’s lifeis hypoxia. Anything which distresses the animaland thus increases its O 2 requirements mayprove fatal. When most of the thoracic cavity isoccupied by abdominal viscera and/or effusion,the animal can only survive by making maximalbreathing efforts and the use of respiratory depressantsedative or analgesic drugs is most unwise.Heavy sedation for diagnostic radiography isparticularly contraindicated. In dogs, phenoth-

INTRATHORACIC SURGERY 497iazine ataractics like acepromazine together withsmall doses of an opioid such as pethidine(meperidine) generally produce sufficient, safesedation, and in cats small (10 mg) doses of pethidineare useful. All animals must be kept underclose observation after any sedative or analgesicpremedication to detect the development of respiratorydistress.Anaesthesia for animals with diaphragmaticrupture may be managed in a variety of ways. Nohard and fast rules can be given and each individualcase must be treated on its own merits. Allcases must be handled very quietly and gentlybefore anaesthesia is induced, and a smoothinduction of anaesthesia with an intravenousagent is advisable. Some animals do not resent theapplication of a face-mask on or near the face andthey may usefully be given oxygen to inhale for2 to 3 minutes before the induction of anaesthesia(‘preoxygenation’). In dogs, whenever it can bedone without undue disturbance of the animal, anintravenous fluid infusion should be set up beforeanaesthesia, otherwise it is set up as soon as possibleduring the course of the operation. This drip isoften needed to remedy the fall in arterial bloodpressure seen when re-expansion of the lungsalters the haemodynamic state of the body (presumablydue to the re-opening of areas of the pulmonaryvascular bed). Endotracheal intubation is,of course, essential in all cases.At the end of the operation no attempt shouldbe made to forcibly expand regions of lung tissuewhich have been in a collapsed state for more thana day, for this leads to pulmonary oedema. The useof a chest drain allows some over expansion ofhealthy, non-collapsed lung to fill the pleuralcavity and encourages collapsed regions to reexpandover a period of time. Chest drainage alsoallows removal from the pleural cavity of fluidwhich often appears in the first 24 to 48 hours ofthe postoperative period.Postoperative pain, which limits breathing torapid, very shallow movements of the chest wall,is best controlled by the injection of pethidine ormorphine, given as required, in doses appropriatefor the size and species of animal concerned.Infiltration of the abdominal incision with 0.25 %bupivacaine is also very effective in alleviatingpain.THORACOTOMY FOR PULMONARYSURGERYOne of the major problems in pulmonary surgeryis the prevention of spillage of secretions or pusfrom the affected part to the remainder of the lung.In man this problem is overcome by drainage orisolation of the affected part of the lung with someform of blocker (usually incorporating a tube fordrainage) or, alternatively, endobronchial tubes,either single or double lumen, provide means ofprotecting the sound lung which can then be ventilatedselectively. In animals, due to the shape of thechest and bronchial tree, most of these techniquesare impossible and reliance has to be placed onpreoperative preparation with antimicrobials andexpectorants to make the lung relatively ‘dry’.Non-irritating anaesthetic agents also play a partin reducing the volume of secretions, while anyremaining can be removed by bronchoscopic aspirationcarried out at frequent intervals through theendotracheal tube.During lobectomy or pneumonectomy, ventilationafter severance of the bronchus and prior to itsclosure presents surprisingly little difficulty andalthough IPPV results in some frothing of bloodthis does not usually obscure the surgeon’s view ofthe bronchial stump. Should it prove to be impossibleto obtain adequate lung expansion while thebronchus is wide open the surgeon may be askedto occlude the bronchial opening with a finger orthumb while the lung is inflated between the layingof bronchial sutures. Provided the minute volumeis kept constant the removal of a lobe or evenof one lung does not result in a significant risein PaCO 2 and indeed the PaCO 2 may actuallyfall, indicating an improvement in the deadspace/tidal volume ratio. There is usually a fall inPaCO 2 as soon as the chest is opened and measureswhich have been recommended to minimize patchyalveolar collapse during constant minute volumeIPPV, such as intermittent manual hyperinflationand continuous manual inflation, are quite ineffectiveand may be harmful. The PaO 2 usuallyremains above 80 mmHg (10.6 kPa) when theinspired gases contain at least 50% of oxygen evenwhen only one lung is available for ventilation.Frequent suction is needed to clear thebronchial tree in bronchiectasis cases and the use

498 SPECIAL ANAESTHESIAof halothane/oxygen or isoflurane/oxygen withoutnitrous oxide has been found to be advantageousin avoiding hypoxaemia when ventilationof the lungs is interrupted for the passage of thesuction catheter. Oxygenation by diffusion continueswhen ventilation is stopped at the end of inspirationbut the PaCO 2 rises until ventilationrecommences.In certain cases, such as operations for theremoval of congenital cysts of the lung, it is advisableto allow spontaneous respiration to continueuntil the pleural cavity is opened. This avoids therisk of overdistension of the cysts with collapse ofnormal lung tissue.Replacement of blood loss during the operationand the maintenance of fluid balance should followthe usual practice for major surgery but afterthe removal of lung tissue animals seem tomake better progress if they are slightly short offluid. Over-transfusion with blood or the administrationof excessive amounts of other fluids isassociated with pulmonary oedema and this isparticularly disastrous after resection of anysignificant amounts of lung tissue. It should benoted that in dogs, traction on the hilum of thelung can cause arterial hypotension; this is not anindication for the administration of fluids – bloodpressure returns quickly to normal when tractionceases.Postoperatively, animals which have had a lunglobe removed should be nursed lying on the soundside until they are able to sit up; this encourages reexpansionof lung remaining on the side of operationand facilitates drainage of any pneumothorax.After pneumonectomy the animal should benursed on the side of operation. The first dose ofpostoperative sedative analgesic should be givenintravenously in order that the patient’s needsmay be more accurately assessed. A routine chestradiograph is advisable before removal of theintercostal drainage tube but it must be recognizedthat positioning for this may distress the animaland under these circumstances it may be necessaryto rely upon auscultation of lung sounds to checkthat the lungs are fully expanded. Instillation of 3to 5 ml/10 kg of 0.25 % bupivacaine into the pleuralcavity on the operated side will usually providemost useful postoperative analgesia for up to6hours.CARDIAC SURGERYCardiac surgery involves more than simple thoracotomy.The drugs used may affect the heart andalter the vascular tone generally. Equally, disordersof the circulatory system may modify theabsorption, excretion and action of anaestheticdrugs. The problems that arise are often peculiar toeach lesion but certain general principles of anaestheticmanagement can be enunciated.All animals should be handled quietly to avoidexcitement and reduce the effect on the heart ofendogenous catecholamine secretion. A small doseof acepromazine is often valuable to calm andfacilitate handling of all species of animal.If an i.v. agent is to be used for the induction ofanaesthesia two points must be noted. First, slowingof the circulation due to the disease processcauses a considerable lag between the administrationof the drug and the development of its effect.This makes it very easy to give too much, for itmay give the impression of drug resistance.Secondly, these drugs may depress the myocardiumand produce peripheral vasodilatation. Inanimals where cardiac output is fixed (e.g. byvalvular stenoses), the vasodilatation may producea very marked fall in arterial blood pressure.The i.v. drug should always be administered veryslowly and in very dilute solutions. However, clinicalexperience indicated that the dangers of i.v.drugs have been overemphasized. The quiet,smooth induction of anaesthesia more than makesup for its supposed disadvantages which are, inany case, much less obvious with the small dosesneeded in properly premedicated patients.Provided it does not excite the animal, O 2 shouldbe administered through a face-mask before anaesthesiais induced, but in every case it should begiven as soon as consciousness is lost. A perfect airwayis always essential and a large-bore endotrachealtube must be introduced as soon as possible.Pericarditis and cardiac tamponade are verycrippling conditions because they limit the cardiacoutput and depress tissue respiration by thewidespread action of raised venous pressure.Associated ascites and pleural effusions reduce thevital capacity and venous back pressure may damagethe liver. Careful preanaesthetic preparation ofthese cases is necessary. Pleural and peritoneal

INTRATHORACIC SURGERY 499effusions must be tapped and fluid retentionreduced by the use of diuretics. Cardiac tamponademust be relieved by paracentesis under localinfiltration analgesia.Much has been written concerning anaesthesiaof healthy animals of various species for experimentalcardiac surgery but little of this is relevant toclinical veterinary practice. Clinical cases presentedfor cardiac surgery for the correction of acquired orcongenital lesions almost invariably have circulatorydisturbances which complicate their management,and in many, failure of medical treatment isthe reason why operation is contemplated. Few veterinarycentres will ever receive enough cases toenable the expertise necessary for their successfultreatment to be developed and the assistance of anexperienced medical cardiac surgery team shouldbe sought to give the animal the best chance of survival.However, some of the simpler lesions may beamenable to correction under moderate hypothermiaby veterinary surgical teams. Even when cardiopulmonarybypass techniques involving anexpert medical perfusionist are needed it is usualfor a veterinary anaesthetist to be involved in thepatient’s general management. The veterinary clinicalanaesthetist should, therefore, be familiar withthe principles of bypass techniques, and of moderatehypothermia, for circulatory arrest.It is probable that most cardiac surgery will becarried out in dogs and the techniques of anaesthesiaused in these animals will be described below.They are not difficult to adapt for other species ofanimal should the need arise. It must be emphasized,however, that in veterinary practice cardiacsurgery is seldom likely to be an economic propositionand it is often undertaken out of an academicinterest in the advancement of knowledge relatingto circulatory disorders generally.UltrasonographyThis technique of investigation can be carried outwithout risk to an animal that can be handled quietlyand the administration of drugs is usuallyquite unnecessary.Cardiac catheterizationMost animals presented for cardiac surgery arefirst investigated by cardiac catheterization.Radiopaque catheters, visible by fluoroscopy, canbe advanced from a peripheral vein into the rightheart and pulmonary artery. By wedging the tip ina pulmonary artery, an indication of left atrialpressure can be obtained. In addition, a needleconnected to a fine tube can be passed throughthe catheter when it is in the right atrium to piercethe atrial septum and measure the pressure in theleft atrium directly. The left ventricle can beentered directly if a catheter is introduced from aperipheral artery.Information is obtained by pressure measurement,by measurement of cardiac output and byblood gas analysis on samples of blood taken fromknown positions of the catheter tip. Angiographyis usually carried out on the same occasion usinglarge film rapid changers or cineradiography.Anaesthesia must not interfere with any of thesediagnostic procedures.After full premedication anaesthesia may beinduced by the careful i.v. injection of small dosesof thiopentone, diazepam/ketamine, or midazolam/propofol,followed by i.v. pancuronium,atracurium or vecuronium, and endotracheal intubationas soon as relaxation of the jaw muscles isobtained. To maintain blood gases as near normalas possible, IPPV is carried out with gas mixturescontaining 20% O 2 in such a way as to maintain thePaCO 2 between 35 and 40 mmHg (4.7 and 5.3 kPa).The use of IPPV overcomes alterations of PaO 2which may result in an uncontrolled way when theanimal is breathing spontaneously. The procedureis usually undertaken in a darkened room and thewise anaesthetist withdraws briefly during theradiation period.Cardiac catheterization is not without risk.Severe arrhythmias and circulatory instability arerelatively common. The anaesthetist must be preparedto deal with these as they arise, for exampleby giving 1–2 mg/kg of lignocaine (lidocaine) i.v.as a bolus to treat tachyarrhythmias.HypothermiaProvided that it has no work to do, heart muscleitself is not harmed by short periods of circulatoryarrest but brain cells are extremely sensitive tooxygen lack and at normal body temperatures of37–38 °C cannot survive if the circulation stops for

500 SPECIAL ANAESTHESIAmore than 3 to 5 minutes. Reducing the temperatureof brain cells depresses their metabolism andenables them to withstand the effects of longerperiods of circulatory arrest. For example, at 30 °Cthe brain will survive and function after a circulatoryarrest of 10 minutes.Body temperature measurementDuring the rapidly changing conditions of bodycooling and rewarming associated with hypothermiatechniques, a temperature measurement madein the mouth or rectum fails to provide an adequateindex of temperature in other regions ofthe body. There is ample evidence, however, thatthe oesophageal temperature at heart level is amost reliable measure of heart and blood temperature.For this reason a suitable calibrated thermometerprobe introduced correctly into theoesophagus, should always be used for temperaturemeasurement.Reactions to coldThe reactions of the body in response to chillingwere well described many years ago by Dripps(1956). In a conscious animal cutaneous vasoconstrictionis the first reaction of the body to a coldenvironment. Adrenaline (epinephrine) is releasedfrom the adrenal glands and this, besides causingvasoconstriction, stimulates cellular metabolismmobilizing glycogen and increasing heat production.Other responses include release of thyrotrophichormone and adrenal corticoids, both ofwhich result in greater heat production. If thesereactions prove insufficient to maintain normalbody temperature shivering occurs and a tremendousincrease in heat production results. Shiveringis by far the most effective means of maintainingbody temperature.As the body cools, the heart rate slows and it isabout halved when body temperature reaches25 °C. This slowing is apparently due to cooling ofthe pacemaker and is accompanied by a prolongationof systole and isometric contraction. Changesin the ECG include prolongation of the P–R intervaland a lengthening of the QRS complex.Elevation of the S–T segment or the appearance ofa wave rising steeply from the S wave heralds theonset of ventricular fibrillation. The onset of ventricularfibrillation during hypothermia is influencedby a number of factors :1. The type of anaesthesia.2. Mechanical stimulation. Stimulation of theheart by catheters in the ventricles or by surgicalmanipulations may induce fibrillation.3. Under-ventilation of the lungs, with aconsequent rise in PaCO 2 and a fall in pH,predisposes to fibrillation.4. Changes in ionic equilibrium of the blood.The relative concentrations of potassium andcalcium are particularly important here.5. Sympathetic discharge. There is someevidence suggesting that blocking sympatheticnerves to the heart protects this organ fromfibrillation under hypothermia.6. Blood pressure. Abrupt falls in ABP givingrise to decreased coronary blood flow can, duringhypothermia, precipitate ventricular fibrillation.The blood flow in the brain, kidney and splanchnicregion is reduced as body temperature falls. Thefemoral vascular bed dilates down to oesophagealtemperatures of about 34 °C, then vasoconstrictionoccurs and later at 20–25 °C a second vasodilatationtakes place. One of the common uses ofhypothermia is in circumstances requiring clampingof the aorta for a considerable time. Afterocclusion lasting more than about 30 minutes, thevasodilatation which follows the release of theclamp is large and lasts as long when the body iscold as when it is warm. Vasoconstrictor substancesor blood transfusion may be necessary tocounteract this effect.A fall in body and brain temperature results in adecrease in cerebral oxygen consumption. At 25 °Cbrain O 2 uptake is about one-third of that at 37 °Cand over this range O 2 consumption is a linearfunction of temperature. A matter of major importanceis the degree of protection afforded to nervoustissue from the effects of circulatory arrest byhypothermia. At 25 °C the circulation can bestopped for 15 minutes without apparent damageto brain cells and for various reasons this time of 15minutes seems to be maximum which can beachieved by surface cooling (between 28 and 25 °Cthe incidence of ventricular fibrillation risessteeply). The EEG begins to change as body

INTRATHORACIC SURGERY 501temperature falls to 36–34 °C. The potential recordedshows a decreased amplitude and large δ-waves appear, particularly in the frontal area, atabout 30 °C. The electrical activity then declinesuntil between 18 and 20 °C no activity is recorded.Moderate hypothermia has several potentiallyharmful effects (Deakin et al., 1988). The O 2 dissociationcurve is shifted to the left resulting in anincreased affinity of haemoglobin for O 2 at a givenpartial pressure of O 2 . This reduced O 2 delivery totissues is partly offset by an increase in freedissolved O 2 by as much as 20% at 30 °C. Hypothermiaincreases muscle tone and, at moderatedegrees of hypothermia, will trigger shiveringwhich can increase O 2 consumption several foldbut is prevented by the use of neuromuscularblocking drugs.Techniques for the production of hypothermiaTechniques for producing hypothermia includebody surface cooling, body cavity cooling, intragastriccooling and blood stream cooling.Before hypothermia can be produced by surfacecooling the animal’s natural defences to cold mustbe obtunded. Otherwise, attempts to reduce bodytemperature are likely to increase rather thanreduce cellular metabolism. The efficacy of bodysurface cooling therefore depends on maintaininga coincident vasodilatation of the superficial bloodvessels and preventing shivering. Fortunately, theanaesthetic agents which affect one reaction generallymodify the other. Chlorpromazine hydrochlorideappears to be the best drug to producevasodilatation and prevent shivering; acepromazinedoes not seem to result in the productionof as marked cutaneous vasodilatation. Onceanaesthesia is induced neuromuscular blockingdrugs can be given to make shivering impossible.Hypothermia by body surface cooling isinduced by immersing the animal in a water bathat 15 to 20 °C and circulating the water around thebody while the trunk and limbs are massaged tomaintain the cutaneous circulation. The animal isremoved from the bath when the oesophagealtemperature is about 30 °C and dried with towels.One of the principal dangers of body surface coolingby this immersion method is the ‘after-drop’when the animal has been removed from the bath.The ‘after-drop’ reduces oesophageal temperatureby up to 2 °C and it is important to allow for thisbecause ventricular fibrillation is common at temperaturesbelow 28 °C. The ‘after-drop’ occursbecause when the animal is removed from the baththe skin and neighbouring tissues are extremelycold. In fact they are much colder than the circulatingblood and as the blood reaches these parts itcontinues to cool long after active cooling measureshave been stopped.In many cases the animal has rewarmed sufficientlyby the end of the operation but if it has notdone so it may be partially immersed in a bath ofwarm water. If surgery is not complete, anaesthesiamay be continued when the body temperatureis above 35 °C.Surface body cooling is a messy, inconvenientprocedure, but it does not involve use of any complicatedapparatus and it can be applied by eveninexperienced personnel with a fair degree ofsafety to animals of below about 70 kg.Intragastric cooling is a slower but much moresophisticated process. A very good, relatively inexpensiveapparatus utilizes an intragastric balloonwhich is introduced into the stomach via theoesophagus after the induction of general anaesthesia.Cold water is circulated through this balloonand reduction of body temperature to below28–29 °C usually takes some 1 to 2 hours. This mayseem a relatively long time but during the coolingprocess ECG leads and blood pressure transducerscan easily be attached and vascular cannulationsmade while the surgical procedure is started.Rewarming can be commenced at any time duringsurgery (without interrupting its progress) by circulatingwarm water through the balloon, andrewarming is more rapid than can be achieved byany other method.Bloodstream cooling is normally regarded asbeing part of the cardiopulmonary bypass techniquebut hypothermia can be produced in thisway with relatively simple equipment. An externalcircuit containing a transfusion warming coiland a roller peristaltic pump is primed with a plasmasubstitute such as Haemaccel and the coil isimmersed in a bath of water maintained at 4–5 °C.Cannulae are inserted into the animal’s femoral orcarotid artery and femoral or jugular vein and theanimal is given 3 mg/kg heparin (using heparin

502 SPECIAL ANAESTHESIAwithout a preservative). The cannulae are thenconnected to the external circuit so that arterialblood is run through the coil and pumped backinto the vein. The animal cools quite rapidly andthe external circulation is stopped when thedesired oesophageal temperature has beenreached. Heparin has a half-life of about 1 hourand to maintain heparinization of the animal it isnecessary to give half the initial dose for each hourof operation.Rewarming can easily be achieved by recommencingthe external circulation with the water inthe water bath maintained at 40 °C. Once the animalhas rewarmed the external circulation isstopped and the heparinization reversed by theadministration of protamine sulphate at the rate of1.5 to 2.0 times the initial dose of heparin.Technique of cardiopulmonary bypassCardiopulmonary bypass enables the heart andlungs to be excluded from the circulation while anadequate blood supply to the rest of the body ismaintained. In order to exclude the heart andlungs from the circulation, the vena cavae orthe right atrium are cannulated and the blood isallowed to flow through these cannulae to thepump-oxygenator or ‘heart-lung’ machine. Havingpassed through the oxygenator to a reservoir it ispumped back into the circulation via a cannula ineither the aorta, or carotid or femoral artery. Theheart-lung machine is provided with a means ofaltering the temperature of the blood beingreturned to the patient as required by the circumstances(e.g. cooling during the bypass procedure,or rewarming at the end of bypass). It is also providedwith a number of pumps which are used toaspirate blood from the heart cavities and pericardiumfor return to the patient’s circulation viathe oxygenator during the bypass procedure.The pumps used for heart-lung machines areusually roller pumps which occlude and milksiliconized tubing against a track and thus causethe blood contained in the tubing to flow along it.The mechanical part of the pump does not comeinto contact with the blood and this minimizeshaemolysis.Modern oxygenators are designed to exposea thin film of blood to a flowing gas mixture separatedfrom it by a plastic film. This allows oxygenationto take place and carbon dioxide to beremoved with minimal blood damage. Whateverthe actual design, the gas input is usually a mixtureof O 2 and CO 2 at a flow adjusted to maintainsatisfactory levels of gaseous exchange. Themachines must, of necessity, have a large surfacearea for gaseous exchange and this leads to considerablecooling of the blood so some form of heatexchanger is always incorporated in the design.In order that blood may be pumped through theheart-lung machine without clotting the patientmust be anticoagulated with heparin beforebypass. The management of the anticoagulation isgreatly assisted by the use of the activated clottingtime (ACT) where 2–3 ml of blood are added to12mg celite which reduces the normal whole bloodclotting time to 90–130 s. Adequate heparinizationis achieved by prolonging the ACT to at least threetimes baseline levels. At the end of the procedureheparinization is reversed with protamine sulphategiven carefully to avoid undesirable sideeffects such as hypotension.Before the patient can be connected to the heartlungmachine air must be excluded from the systemby filling with fluid (‘priming of the system’).A typical prime allows the administration of 30 to50 ml/kg of 5% dextrose or Ringer’s lactate solutionfrom the circuit to the patient when bypasscommences. The resulting haemodilution reducesthe viscosity of the blood and enables better bodyperfusion to be achieved. The high flow rates usedtoday in cardiopulmonary bypass and meticulousattention to blood replacement prevent any acidosisfrom suboptimal perfusion of some tissuesdeveloping, so that it is not necessary to administersodium bicarbonate to correct acidosis at theend of the procedure.Anaesthesia for open heart surgery maybe administered in many ways and it is probablethat each centre carrying out this type of surgeryhas its own favoured technique. All methodsare chosen to cause minimal changes in heart rateor blood pressure, and to have no direct depressanteffect on the myocardium. Recently, the techniqueof low flow cardiopulmonary bypass insmall dogs has been recorded (Lew et al., 1997)with 6 out of 6 dogs being successfully weanedfrom bypass.

INTRATHORACIC SURGERY 503Premedication consists of administering effectivedoses of sedative drugs. Agents such asdiazepam, midazolam, morphine, hyoscine andpapaveretum may be used in full doses and often asmall dose of atropine is included with them.Heavy sedation helps to allay fear, induction ofanaesthesia is smoother and total drug dosageduring anaesthesia is reduced. It is probable thatpropofol is the best induction agent, administereduntil the eyelash reflex is just abolished. Somesmall reduction of arterial pressure occurs but isseldom of significance if the rate of administrationof the intravenous agent is slow. IPPV is commencedafter injection of a neuromuscular blockingdrug (e.g. atracurium, vecuronium), hasabolished spontaneous breathing.An intraoesophageal thermometer probe isplaced middle of the thoracic oesophagus andother temperature probes are placed in thenasopharynx and on the tympanic membrane. Ani.v. infusion is established and closed bladderdrainage is set up with a self-retaining urinarycatheter or, in male animals, with a catheterretained in position with a stitch. A catheter forarterial pressure monitoring is introduced andanother for CVP measurement is passed via thejugular vein. ECG leads using needle electrodesare attached and the ECG is monitored continuouslythereafter. The arterial and venous cathetersare attached to their respective manometer lines,including 3–way taps for easy withdrawal ofblood samples.For the maintenance of anaesthesia IPPV isusual with minimal infusions of propofol (2.5 to3.0 mg/kg) which can be added to the pump-oxygenatorduring total bypass. During total bypasslung ventilation is stopped and the lungs held atan airway pressure of about 10 cmH2O (1 kPa) toprevent collapse. Typically, the oxygenator gasesconsist of 97% O 2 with 3% CO 2 and an inhalationagent such as isoflurane or halothane may beincluded to assist in vasodilatation. Nitrous oxideis usually reintroduced for IPPV after coming offbypass as soon as the arterial blood saturation issatisfactory.In addition to the management of anaesthesia,the anaesthetist plays an important role in monitoringrespiratory and circulatory function andthe correction of any departures from optimum asmay occur. The preperfusion period is often themost hazardous. The heart lesion is uncorrectedand induction of anaesthesia may produce a furtherdeterioration in the animal’s condition. Whenthe mediastinum is opened and the heart and greatvessels are manipulated by the surgeon the effectivenessof the heart’s action may be temporarilyimpaired. Arrhythmias are easily provoked bycontact between the heart and suction cathetersand swabs or retractors may obstruct the venousreturn or the flow in the pulmonary artery.Constant observation of the arterial pressurewave-forms as displayed on an oscilloscope, andof the ECG are, therefore, essential. Before goingon bypass the surgeon may have to be asked tostop activities until the heart has recovered normalrhythm.Arrhythmias of all kinds may be seen, but areoften only transient, resolving spontaneouslywhen the cause is removed. Bradycardia may bedue to hypoxia, which must be eliminated as acause before atropine is given. In the absence ofsinus rhythm isoprenaline may be needed; anincomplete heart block is also treated with thisdrug. Myocardial irritability may be due tohypokalaemia and is often corrected by the veryslow intravenous injection of potassium chloride,but if this does not produce the desired result lignocainemay have to be given. It is most importantto have facilities for rapid estimation of blood electrolytesreadily available. Vary rarely, cardiac irritabilitymay be the result of metabolic acidosisneeding treatment with i.v. sodium bicarbonate.During perfusion the haematocrit falls becauseof the diluting effect of the pump prime and theaim is to keep it between 20 and 25% by addition ofblood to the pump circuit as needed. Some redistributionof body fluids occurs and urinary outputusually increases so that additional priming fluidhas to be added. Diuretics (e.g. frusemide) aregiven if the urinary output is unsatisfactory andpotassium is given to replace that lost in the urine.Lung ventilation is recommenced immediatelybefore perfusion is stopped. Caval snares arereleased and blood fills the heart and enters thelungs. The surgeon uses this blood to ensure thatair is displaced from the left heart before allowingthe systemic circulation to depend on the left ventricularcontraction. Proper cardiac filling is, of

504 SPECIAL ANAESTHESIAcourse, essential and blood is transfused from thepump circuit or by i.v. infusion until atrial pressuresare adequate. Initially atrial filling pressuresmay have to be increased slowly to 15 mmHg(2kPa) or until no further improvement in arterialpressure occurs, and inotropic support (adrenaline)may be needed but usually over a period ofabout 30 minutes a much lower atrial filling pressureof 5–6 mmHg (0.7–0.8 kPa) becomes effective.Perfusion is controlled by the perfusionist toproduce an adequate tissue blood supply withoutexcessive flow rates which result in destruction ofred blood cells and cause a greater incidence ofpostoperative bleeding. It is possible to reduce theperfusion rate needed by inducing hypothermiaand, consequently, cardiopulmonary bypass withmoderate hypothermia (reduction of central bodytemperature to 30–32 °C) is commonplace. Manysurgical units use additional profound hypothermiaof the myocardium, cooling it to 15–18 °C .There are many variations for the technique ofperfusion but typically after heparinization (about3 mg/kg) and introduction of the necessarycatheters and snares, cardiopulmonary bypass isbegun without arrest of the patient’s own circulation.Systemic cooling is instituted and once thedesired body temperature is reached IPPV is discontinuedand a left ventricular vent is placedthrough the apex of the ventricle. The caval snaresare then drawn tight and the aorta is crossclampedto produce total bypass. The heart is electricallyfibrillated with low voltage alternatingcurrent shock and the aortic root perfused withcold cardioplegic solution to cause rapid arrest ofthe heart in diastole. At the same time external cardiaccooling through the pericardial sac is commencedvia a recirculation cooling system usingcold saline. The cardioplegic solution containsbuffered potassium, calcium and magnesium saltswith heparin and procaine. The cardiac musclenormally becomes quite flaccid at 15–18 °C givingabout 30 minutes operating time.Rewarming is accomplished by removing theaortic clamp and allowing blood, warmed in thepump-oxygenator, to perfuse the animal, includingthe coronary circulation. The myocardiumrecovers in 10–20 minutes and goes into coarse fibrillation.The application of a direct current shockof about 45 J applied directly to the heart restoresnormal rhythm and the caval snares are released.Supportive bypass is maintained while the rightatrial pressure is adjusted to about 5 mmHg (0.7kPa) by fluid replenishment as needed. Bypass isthen discontinued and protamine sulphate isgiven over a 10 minute period while blood is transfusedfrom the heart-lung machine into the animalto maintain the right atrial pressure. Any tendencyto arterial hypotension in spite of an adequateright atrial pressure is treated by the infusion of aweak solution of adrenaline (1: 50 000 in Hartmann’ssolution) given at the rate of 2–3 drops perminute or administered by an infusion pump.Postoperative careAll animals subjected to open heart surgery withcardiopulmonary bypass should be treated in anintensive care situation with continuous nursingattention for at least the first 24 hours postoperation.During this time arterial and venous pressures,heart and respiratory rates, PaO 2 and PaCO 2should be recorded at 30 minute intervals while acontinuous watch is kept on the ECG and urinaryoutput.Surgical bleeding is not uncommon andtreatment may require reopening of the chest.Although the pericardium is seldom sutured, cardiactamponade should be suspected when ABP islow, the CVP is high and the urinary output poor.If clotting studies produce normal results, any animalscontinuing to bleed from the skin wound orinto the chest require surgical re-exploration.Poor tissue perfusion, low output states andmassive blood replacement together with lung collapsemay all lead to acid–base changes necessitatingthe administration of sodium bicarbonate.Emboli may be introduced into the circulationat any time during bypass and surgery. They maybe particles of silicone antifoam from the oxygenator,air or oxygen, or tissue debris. The mostimportant results of such embolism are neurologicaland it can produce anything from transientmonoplegia to total brain death.Sedation and pain relief are particularly importantfor the facilitation of nursing care for the first24 hours after surgery and i.v. frusemide (1 mg/kg)may have to be given to prompt a satisfactory urinaryoutput of 0.5 to 1 ml/kg/hour.

INTRATHORACIC SURGERY 505Chest drains are usually removed some 24 to 36hours after operation and if oedema develops itmay be necessary to administer concentrated plasmato counteract the effects of haemodilution atthe time of bypass.Insertion of pacemakersPacemakers are devices which ensure that theheart beats sufficient times per minute regardlessof the intrinsic rhythmic activity. They are insertedfor different types of conduction deficits and usuallyonly when an animal is showing symptoms.Most pacemakers used in veterinary practice areobtained from human cadavers prior to cremationof the body.Temporary pacemakers have wires passedthrough the veins to rest in the right ventricle.There are some needle electrodes which can beinserted through the chest wall but these are foremergency use only. Oesophageal pacing is alsopossible. Permanent pacemakers are frequentlyinserted under general anaesthesia. The pacingwire passes via the jugular vein and tricuspidvalve to the right ventricle where it is anchored tothe trabeculae by some kind of hook. A subcutaneouspocket is then constructed for the ‘pacemakerbox’ or it is placed in the abdominal cavity. Theyare powered by various types of battery. Less commonlypermanent pacemakers are implanted intothe epicardium via a min-thoracotomy.Pacemakers have one of three modes of operation.They may be fixed rate and have the advantageof simplicity, but are now seldom used(Fig.19.4). Demand pacemakers have the ability tosuppress cardiac pacemaker activity if the heartrate is adequate but cut in if the rate falls below apre-set minimum; they are the most common kind.Sequential pacemakers are complex, with atrialand ventricular electrodes, usually fired by the Pwave of the ECG; as yet, they have not been extensivelyused in veterinary medicine.Anaesthesia for fitting of pacemakers usuallypresents no difficulty but the surgeon shouldavoid diathermy and the pulse should be monitoredby a precordial or oesophageal stethoscope,or a peripheral pulse monitor which is not obliteratedby electrical interference. It is advisable tohave an isoprenaline or dopamine infusion readyfor use should bradycardia develop in the anesthetizedanimal before the pacemaker can be madeoperational.Many anaesthetists do not usually put temporarypacemakers in animals with stable 3rd degreeA–V block because these animals seem to maintainstable haemodynamics when anaesthetized.Should pharmacologic support be needed, dopamineat about 10 µg/kg/min usually produces asatisfactory increase in the heart rate. When facilitiesare available, however, most anaesthetists puta pacemaker in animals with sick sinus syndromeor in cases where there is concern about the stabilityof the slow rhythm before anaesthesia isinduced.REFERENCESABFIG.19.4 A:ECG with demand pacemaker. These havean internal ability to suppress their activity if the heart rateis adequate but ‘cut in’ if the spontaneous heart rate fallsbelow a preset minimum. B:ECG with a fixed ratepacemaker.These are seldom used today;ECG complexesare usually abnormal during pacemaker function becauseof depolarization commencing at an ectopic site.Deakin, C.D., Knight, H., Edwards, J.C., Monro, J.L.,Lamb, R.K., Keeton, B. and Salmon, A.P. (1988)Induced hypothermia in the postoperativemanagement of refractory cardiac failure followingpaediatric surgery. Anaesthesia 53: 848–853.Dripps, R.D. (1956) The Physiology of InducedHypothermia. National Research Council PublicationsNo. 451. Washington DC: National Research Council.Lew, L.J., Fowler, J.D., Egger, C.M., Thompson, D.J.,Rosin, M.W. and Pharr, J.W. (1997) Deep hypothermiclow flow cardiopulmonary bypass in small dogs.Veterinary Surgery 26: 281–289.

Prevention andmanagement of anaestheticaccidents and crises20INTRODUCTIONWhen the profound physiological changes initiatedby drugs used in anaesthesia are considered itis surprising that serious accidents and emergenciesare not more common. Familiarity with techniquesand drugs can lead to a nonchalant attitudebut the anaesthetic may be a greater hazard to thelife of the animal than is the operation. Duringanaesthesia some accidents occur suddenly andthe reason for the mishap must be recognizedimmediately so that the appropriate remedy canbe applied at once. Other incidents are less dramaticand their results may only become apparentduring the postoperative period. Moreover, onekind of emergency may lead to another. Few seriousemergencies are truly sudden in onset: theyare usually the result of summation of variousproblems which may have been overlooked. Mostdisasters can be avoided by critical assessment ofpotential hazards of the particular situation and bysuitable monitoring that enables potential problemsto be recognized before they progress to seriouslylife-threatening situations. Prevention is notalways possible and serious problems can ensue ifthe anaesthetist is not always ready to apply theappropriate remedy in any difficult situationwhich may arise. Anaesthesia is still an art, andthere is no substitute for experience, but even inexperiencedanaesthetists can deal successfully withmost mishaps if aware of the nature of the morecommon accidents and emergencies.The final result of most serious or fatal anaestheticaccidents is that of tissue hypoxia. Brain cellsare particularly easily damaged, and even mild hypoxiamay result in a loss of intelligence and changein temperament following anaesthesia, whilst amore prolonged insult results in coma, and possiblydeath. Hypoxia of the myocardium will reducemyocardial contractility and may, particularly ifcoupled with hypercapnia, sensitize the heart toother stimuli and finally produce cardiac arrest orfibrillation. Lack of oxygen will also damage theliver, kidneys and even somatic muscle, bothdirectly and by increasing the toxic effects of anyanaesthetic used, but the results of such damagemay not become obvious until well into the postoperativeperiod. Haemoglobin desaturation of arterialblood reduces the O 2 supplies to all tissues andis, therefore, very important to the anaesthetist.HAEMOGLOBIN DESATURATIONThe diagnosis and treatment of falls in O 2 transportby haemoglobin in arterial blood (desaturation)requires rapid, effective correction duringanaesthesia. New technologies such as pulseoximetry have revolutionized its early recognition.When it occurs the immediate response consists ofrapid performance of the well-known ‘Airway,Breathing and Circulation’ check routine (seep. 517) and, where possible, provision of anincrease in inspired O 2 . Next, attention should be507

508 SPECIAL ANAESTHESIAfocused on differential diagnosis of more definedcauses of hypoxia.Arterial desaturation can be detected directlyby observation of the colour of the patient’smucous membranes as well as by monitors such asthe pulse oximeter. The clinical sign of cyanosis isdependent on a number of factors other than arterialdesaturation. These include anaemia, ambientlighting and superficial pigmentation. Cyanosismay not be seen at all in anaemic or shocked animals.The coexistence of cyanosis with a pulseoximeter reading that indicates adequate saturationmay be due to local stasis of blood in theperipheral tissues (which is usually distinguishablefrom central cyanosis by examination of thecolour of the tongue). The colour of lightingsources in the room can also give a false impressionof cyanosis or normality. This is well known:shops use longer wavelength light to make counterdisplays of meat look pinker and fresher.Reasons for arterial desaturation which theanaesthetist needs to consider are given below.APPARATUSRoutine following of a checklist such as that givenbelow before administration of any general anaestheticwill prevent mishaps occurring from malfunctioningor misuse of equipment.Anaesthetic machinesBefore administering any anaesthetic, but especiallythose involving general anaesthetic methods:1. First:(i) Note any labelling or service informationattached to any machine by service engineers and,if appropriate, switch on electrical supply.(ii) Switch on and note whether any O 2analyser (if fitted) is calibrated and if so, whether itis functioning correctly.2. Gas supplies:(i) Check the connections to an O 2 supply. Ifconnected to a pipeline confirm correct connectionwith a ‘tug test’, ie a sharp pull at the connection,and inspect for any attempt to connect incorrectlyby nursing or other staff.(ii) If connected to a pipeline, switch on spareO 2 cylinder (‘tank’ in North America) and checkthat the contents are adequate. For non-pipelinemachines switch on the ‘in use’ cylinder and checkits contents, turn off the cylinder, repeat the checkon the reserve cylinder and after turning it off reopenthe ‘in use’ cylinder.(iii) If N 2 O use is intended check that themachine is connected to a N 2 O supply. For nonpipelinemachines check the contents of the N 2 Ocylinder.(iv) If intended to use an air supply (pipeline orcylinder) check the machine is connected to it.(v) If a CO 2 supply is attached to the machineconfirm that it is turned off.(vi) Make sure that blanking plugs are fitted toall empty or unused cylinder yokes.3. Flowmeters:(i) Check that all flowmeters move freelythroughout their range.(ii) Confirm that with O 2 flowing at 5 l/minany O 2 analyser fitted reads 100%.(iii) Make sure that all flowmeters are turnedoff.4. Emergency O 2 bypass control:(i) When the bypass control is operated see thatflow occurs without significant drop in thepipeline or cylinder pressure.(ii) Check that the flow ceases when the controlis released.(iii) If fitted, note that the O 2 analyser reads100% when the oxygen is flowing.5. Vaporizers:(i) Check that the vaporizers for the requiredvolatile agents are present, locked to the back- bar,correctly seated and adequately filled.(ii) Make sure that the filling ports of thevaporizers are tightly closed and that the controlsof each vaporizer move throughout their range.(iii) If the back bar is protected by pressurerelief valve, with an O 2 flow of 5 l/min occlude the

ANAESTHETIC ACCIDENTS 509common gas outlet, note that the flowmeterbobbin dips and that there is no leak from thefilling ports of the vaporizers.6. Breathing systems:(i) Ensure that the breathing system is correctlyassembled with all the connections tight.(ii) Listen for any leaks when gas is flowingand the system is pressurized by occlusion of thecommon gas outlet.(iii) Check that the pressure relief valve(s) openand close fully.(iv) By breathing through the system confirmthat in any circle system the unidirectional valvesoperate correctly.(v) When endotracheal intubation is contemplatedcheck that tubes of appropriate sizes areavailable and that their cuffs do not leak wheninflated with air.7 Ventilators:(i) Make sure that the ventilator is correctlyassembled and that all the connections are tight.Set the controls and switch on to check thatadequate pressure is generated in the inspiratoryphase.(ii) Ensure that an alternative means ofventilation (e.g. manual squeezing of a reservoirbag) is readily available.(iii) Check that the pressure relief valve operatescorrectly when the patient port is occluded.(iv) Ensure that any disconnection alarmwhich is present is operating correctly (if necessaryconsult the manufacturer’s instructions).8. Scavenging:Make sure that any scavenging system is correctlyattached and functioning.Ancillary equipment(i) Confirm that all laryngoscopes likely to beneeded are in working order.(ii) Check that suction apparatus is availableand able to generate adequate negative pressurerapidly.(iii) Check that appropriate monitoringequipment is present, switched on and calibratedwith appropriate alarm limits set.Checks such as these occupy very little time andshould be repeated before each anaesthetic administration.AIRWAYObstruction or excessive resistance within thepatient breathing circuit of the apparatus will havethe same result as obstruction of the patient’s ownairway. A spontaneously breathing, lightly anaesthetizedanimal commonly responds to respiratoryobstruction by making frequent violent attemptsto breath, but the short vigorous inspiratory effortsmake the situation worse as they increase theresistance created by the obstruction. Unfortunately,these vigorous movements can be taken bythe inexperienced anaesthetist to mean that anaesthesiais too light and the result may be an attemptto increase anaesthetic depth. The response toobstruction in a deeply anaesthetized animal isusually much quieter, ventilation simply becomesinadequate to maintain respiratory homeostasis.If a breathing system including a reservoir bagis in use for a spontaneously breathing animal, thebest guide to the patency of the airway is theexcursion of this bag, but if one is not present inthe system, diagnosis of airway obstruction maybe difficult. Although complete obstruction is usuallyfairly easy to detect, a partial obstruction isoften not so obvious and may result in the insidiousonset of hypoxia and hypercapnia.In animals connected to a ventilator, observationof its pressure or volume measuring dialsoften enables obstruction of the airway to bequickly recognized and some machines havedevices which warn of obstructions or changes ingas flow into or out of the lungs.In the non-intubated animal respiratory obstructionis usually due to the base of the tongue orthe epiglottis coming into contact with the posteriorwall of the pharynx. This type of obstruction isovercome by extending the head on the neck andpulling the tongue forwards out of the mouth. Inpigs over-extension of the head on the neck will

510 SPECIAL ANAESTHESIAFIG.20.1 Acute flexion of a dog’s neck for radiographyleading to kinking of the cuffed endotracheal tube withcomplete obstruction of the airway.also cause respiratory obstruction and in these animalscare should be taken to keep the head in anormal position (‘sniffing for food’) in relation tothe neck. Horses have a naturally good airway andseldom, if ever, suffer from respiratory obstructionof this nature.Brachycephalic dogs may develop respiratoryobstruction due to the ventral border of the softpalate coming into contact with the base of thetongue. Many brachycephalic breeds are almostunable to breathe through their nostrils andobstruction can only be overcome by endotrachealintubation. The main problem in these breedsoccurs during recovery, when the semiconsciousdog will not tolerate an endotracheal tube. Ideally,anaesthetic agents which ensure a very rapidreturn to consciousness should be used to reducethis danger, but spraying of the larynx with a localanalgesic (4% lignocaine) at the end of the anaestheticmay enable the endotracheal tube to be toleratedfor a longer period.Large blood clots may accumulate in the pharynxafter tonsillectomy, tooth extraction or endotrachealintubation when the tube has been passedthrough the nostril. These blood clots must befound and removed at the end of operation. Animalsunconscious after nose and throat operationsshould be placed in a position of lateral decubitusduring the recovery period and kept under observationuntil fully conscious and able to safeguardtheir own airway by coughing and swallowing.Camelids (e.g. llamas) are often compulsorynasal breathers and the posterior nares can becomeblocked by the soft palate if this comes to lie dorsalto the epiglottis. This can occur at any time in nonintubatedllamas, but more often it is encounteredafter extubation. Inducing the animal to swallowcauses the palate to resume its normal position. Ananimal can usually be induced to swallow by lighteninganaesthesia and introducing a small-borestomach tube into the oropharynx.The fact that an endotracheal tube is in the tracheadoes not necessarily mean that the airway isclear. Endotracheal tubes may kink, particularly ifthe head is flexed on the neck (Fig. 20. 1); they maybecome blocked with mucus and in the case ofcuffed tubes a faulty cuff may actually occlude theend of the tube, or the pressure inside the cuff mayobliterate the tube lumen (Fig. 20.2). During anaesthesiawith N 2 O cuffs can become overdistendedby diffusion of N 2 O into a cuff that has originallybeen inflated with air.An overlong endotracheal tube may pass downone bronchus (usually the right) effectively obstructingthe airway to the other lung. Obstructionmay also be due to an animal biting on the tube.An uncommon but serious cause of respiratoryobstruction in horses is impaction of the epiglottisin the glottic opening. This may occur during ‘blind’intubation in young horses and also in sheep,when a soft, flexible epiglottis is forced backwardsinto the glottic opening by the forcible passage ofan endotracheal tube. Unless the epiglottis is dislodgedto its normal position by the withdrawal ofthe tube at the end of anaesthesia, it can give rise toserious respiratory obstruction in the recoveryperiod until either coughing occurs, or the cause ofthe obstruction is recognized and overcome byhooking the epiglottis out of the airway with atube passed through the nostrils.In horses, oedema of the upper respiratory passagesdevelops during general anaesthesia if the

ANAESTHETIC ACCIDENTS 511FIG.20.2 Occlusion of a soft-walled endotracheal tube by overinflation of the cuff forcing the wall inwards until thelumen is almost obliterated.This picture was obtained by inflating the cuff with the tube inside the barrel of a plasticsyringe.head is in a dependent position or if the jugularveins are partially occluded for any length of time.This can result in serious respiratory obstruction inthe recovery period that can only be relieved byendotracheal intubation, preferably with a nasaltube.Animals suffering from laryngeal paralysis ortracheal collapse may obstruct during the recoveryperiod when the increased effort of breathingtends to draw the sides of the larynx and/or tracheatogether. As with the brachycephalic breedsof dogs, it may be necessary to leave an endotrachealtube in place longer than would otherwisehave been necessary.LARYNGEAL AND BRONCHIAL SPASMLaryngeal spasmLaryngeal spasm appears to be seen much morecommonly than bronchial spasm, but both conditionscan occur together during general anaesthesia.Laryngeal spasm can, in theory, occur in allanimals but it is most common in cats and pigswhen attempts are made to force them to breathehigh concentrations of inhalation anaesthetics duringinduction of anaesthesia before the protectivelaryngeal reflexes have been subdued.Another common complication of anaesthesiain cats is laryngeal ‘crowing’ – the crowing noisebeing caused by partial spasm of the vocal cordsdue to their irritation by a blob of mucus, saliva,blood or vomit. The incidence of this post-extubationcomplication has fallen since the introductionof endotracheal tubes manufactured from substancesmore inert than red rubber. When it persistsafter aspiration of foreign material from thevocal cords, i.v. or oral steroid (e.g. dexamethasone0.3 mg/kg) may relieve it.In horses laryngeal spasm is rare, but obstructionoccurs when the soft palate becomes displacedfrom its normal position under theepiglottis. This situation often arises followingextubation and it is important that the horse swallowswhen the endotracheal tube is removed for,as in camelids, this act restores the soft palate to itsnormal position. Endotracheal tubes are best notremoved until gentle manipulation of the tube orlaryngeal region of the neck is seen to induce thehorse to swallow.When laryngeal spasm is very troublesome thebest treatment is to administer a neuromuscular

512 SPECIAL ANAESTHESIAblocking agent in order to relax the spasm, andthen to intubate with an endotracheal tube.Attempts at intubation by forcible passage of thetube without the aid of neuromuscular blockerswill usually be unsuccessful and will prolong thespasm. Although deepening of anaesthesia itselfmay relax the spasm this can be hazardous.Repeated attempts at forcible intubation through aclosed glottis can result in oedema of the mucousmembrane necessitating tracheostomy. Sprayingof the larynx with 4% lignocaine hydrochloridedoes not produce instant relaxation of the cordsand may result in postanaesthetic problemsfrom their desensitization causing difficulties inswallowing.Bronchial spasm‘Bronchial spasm’ or constriction of the bronchiolesis uncommon but occasionally seen in allkinds of animal. Ruminants appear to be particularlyliable to develop this complication due tounsuspected regurgitation and inhalation of ruminalfluids. Bronchial spasm may also be initiatedreflexly during light anaesthesia by stimuli fromthe site of operation and there is some evidencesuggesting that passage of blood with a low P 2 O 2and high PaCO 2 through the brain causes bronchoconstriction.The first warning sign that bronchial spasmis imminent is usually a bout of coughing and ifan endotracheal tube is not in use the larynxcloses. Complete respiratory arrest follows. Thechest is rigid and the lungs can only be inflated bygreat pressure on a rebreathing bag. While thismay produce an adequate inspiratory volume, thepassive recoil of the lungs and chest wall may beinadequate to provide adequate expiratoryvolume. If a second breath is delivered beforecomplete expiration the phenomenon of ‘stacking’occurs, with increased thoracic gas volume, alveolardistension and increased risk of barotraumaand reduced cardiac output. Thus the animal withsevere bronchospasm should be ventilated with aslow rate allowing a prolonged expiratory time.In the extreme situation virtually no expirationoccurs and pressure on the chest wall may be lifesaving.When untreated, cyanosis sets in and issoon replaced by a grey pallor of the mucousmembranes. If not in robust condition the animalmay die, but usually the severe hypoxia releasesthe spasm and the animal gasps. The gasp is followedby normal spontaneous respiration and theanimal recovers. Unfortunately, bronchial spasmmay recur if the stimulus responsible for the firstattack is still present. In all cases the anaesthetistmust ensure that the upper airway is clear and thatwhenever possible the first gasp of the animal willbe of an O 2 enriched atmosphere.If it is necessary to treat bronchospasm withdrugs because other procedures have been unsuccessful,adrenaline is the drug of first choice asbeing the one most likely to relieve the spasm. Insmall animal patients an i.v. loading dose of 2.5 to5 ml of 1:10 000 followed by an infusion may beused; these doses need to be scaled up appropriatelyfor larger animals.ASPIRATION OF MATERIAL FROM THEOESOPHAGUS AND STOMACHThis accident occurs more frequently than is commonlyrealized for material from the oesophagusand stomach may reach the pharynx as a result ofvomiting or passive reflux. In either case the primaryproblem is respiratory obstruction, possiblyaccompanied by bronchospasm if foreign materialhas penetrated deeply enough into the lungs.Inhalation pneumonia may manifest itself over thenext few days.In those animals that can vomit, it is an activeprocess either during induction or recovery. It isoften preceded by swallowing or ‘gagging’ movements(sharp rhythmic contractions of the abdominaland thoracic muscles); these contractionsincrease intra-abdominal pressure and force gastricor oesophageal contents into the pharynx.When active vomiting occurs during the inductionof anaesthesia, the protective mechanisms oflaryngeal closure, coughing and breath holdingare usually present and the accident should nothave dire consequences, All that is necessary isto clear the pharynx of vomited material, byswabbing or suction, and to allow the animal tocough vigorously before proceeding with furtheradministration of the anaesthetic. The dog, however,has very weak protective reflexes and in afew cases, particularly when vomiting occurs dur-

ANAESTHETIC ACCIDENTS 513ing the recovery period and the dog is still sleepy,these reflexes fail to protect the airway so thatinhalation of vomited material occurs. In suchcases it may even prove necessary to re-anaesthetizethe dog in order to use vigorous suction toclear the tracheobronchial tree.It is obvious that if anaesthetics are not given toanimals whose stomachs might contain food thenaspiration is unlikely to occur, but this is a counselof perfection which cannot always be realized.Clearly, it can never be achieved in ruminants andin simple stomached animals the stomach maycontain material many hours after the eating of ameal, particularly if an accident has occurred inthe meanwhile or if the animal has gone intolabour.Passive regurgitation is most commonly seen inruminant animals but it also occurs in horses, pigs,dogs and cats. It usually happens when the animalis in a head-down position, or lying horizontallyon its side, and relaxation is induced by deepanaesthesia or the use of neuromuscular blockingdrugs. In these circumstances the protective reflexesare not active and aspiration occurs all tooreadily. In deeply anaesthetized ruminants anyincrease in intra-abdominal pressure will forcefluid ingesta up the oesophagus into the pharynx,and this type of regurgitation is frequently seen inadult cattle becoming recumbent after induction ofanaesthesia. To prevent regurgitation in cases ofequine surgical colic the stomach should bedecompressed by the passage of a stomach tubeprior to the induction of anaesthesia. It is almostimpossible to pass a tube into the stomach of ananaesthetized horse.In cases of oesophageal dilation or obstructionthere may be an accumulation of fluid in theoesophagus, while the stomach may contain fluidmaterial if there is an obstruction of the pylorus orsmall intestine. The most certain way of preventingthe aspiration of material from the oesophagusand stomach is to perform endotracheal intubationwith a cuffed tube immediately anaesthesia hasbeen induced. In the case of small animals, keepingthe head raised after induction of anaesthesia,together with rapid intubation of the trachea andcuff inflation will completely prevent the dangerof inhalation from passive regurgitation, but this isobviously not practicable in ruminants.Often, the first sign that aspiration has occurredis the unexpected appearance of cyanosis, dyspnoeaand tachycardia. The severity of theconsequences depends on the quantity of fluidaspirated and extent of the lung regions involved.Immediate treatment consists of thorough aspirationof the tracheobronchial tree – although this ismore easily advised than performed. Oxygenshould be administered and attention directedtowards the relief of bronchiolar spasm. If, afteroperation, the animal develops bronchopneumoniathe appropriate treatment must be instituted(antimicrobials, corticosteroids etc.).TracheostomyThe obvious treatment of respiratory obstructionis to locate it and remove the cause, but this is notalways possible and occasionally in cases of upperrespiratory obstruction an emergency tracheostomyis required to save the animal’s life.In a cat, a 14 gauge needle or catheter, placedpercutaneously directly into the trachea, if possiblethrough the cricothyroid membrane when theobstruction is cranial to this, provides an adequateshort-term airway. In small dogs (up to 5 kg)10gauge catheters or needles may be used in a similarmanner. In all but these small animals the sizeof such airways is totally inadequate for more thanone or two minutes but may be sufficient to sustainlife whilst a surgical tracheostomy is carried out.Curved plastic tracheostomy tubes or cannulae(Fig. 20.3) are available in sizes suitable for surgicalplacement in most dogs. They are insertedthrough the cricothyroid membrane, between twotracheal rings or by slitting a tracheal ring longitudinally.Once such a tube is in place in a dog or othersmall animal, the patient should be under constantobservation as the tube may become dislodged orblocked by folds of skin, secretions, or flexure ofthe neck.In the horse, tracheostomy is much easier tocarry out, and if necessary can provide a safe airwayfor a long period of time. In emergency, or forshort term use, narrow curved tubes (Fig. 20.4) aresuitable. On superficial examination these tubesmay appear to provide far too small an airway, butthey are fully effective in such situations. For moreprolonged use a tracheostomy tube which can be

514 SPECIAL ANAESTHESIAspasm but in most other species of animal it ismade necessary by pathological obstructions ofthe airway which prevent endotracheal intubation.In many cases, therefore, the requirement canbe foreseen and equipment for tracheostomy keptreadily available.BREATHINGAPNOEAFIG.20.3 Disposable tracheostomy tube.This type oftube is suitable for dogs,cats,sheep,goats and small calves.removed and cleaned is employed. These are oftenformed of interlocking pieces for ease of removaland replacement.It must be pointed out that the need for anemergency tracheostomy is rare. In the cat it maybe required because of severe, persistent laryngealApnoea during anaesthesia is very common andits successful treatment depends on the originalcause. Although respiratory arrest is obvious, it isoften preceded by respiratory insufficiency, whichis much more difficult to assess. In either case, theimmediate requirement is that oxygenation of thetissues should be maintained, so as soon as theproblem is diagnosed the anaesthetist shouldcarry out the following routine:1. Check the airway and, if necessary take stepsto clear it.2. Apply artificial respiration (ensuring there isno anaesthetic in the inspired gas).3. Check the pulse.Assuming that the circulation is adequate, inthe majority of cases steps 1 and 2 should preventfurther hypoxia and hypercarbia, and give theFIG.20.4 A laryngotomy tube for a horse.These tubes are intended for insertion through the incision shouldobstruction develop after a laryngoventriculectomy,but they may be used as emergency tracheostomy tubes because theycan be easily slipped through an incision between the tracheal rings.

ANAESTHETIC ACCIDENTS 515anaesthetist time to assess the problem and applyfurther measures accordingly. The commonest reasonfor the failure to resuscitate an apnoeic animalis delay in instituting artificial ventilation. It mustbe emphasized that there are no circumstances inwhich such ventilation is contraindicated in thetreatment of apnoea.The efficiency of artificial ventilation in anemergency depends on the apparatus availableand size of the patient. Where anaesthetic systemsutilizing reservoir bags are being employed it ispossible to ventilate by squeezing the bag, but otherwiseresuscitation is more difficult. Self-fillingbag/valve units such as the Ambu bag (Fig.20.5)are useful to ventilate small animals via a nonrebreathingvalve attached to a facemask or endotrachealtube. Ventilation is with room air but, if itis available, extra oxygen may be added to theinspired gas. These units are excellent in emergenciesaway from operating room areas, and shouldbe part of any portable resuscitation kit for smallanimals. Where only an endotracheal tube may beavailable a dog or cat can, in an emergency, be ventilatedby a person blowing gently down the tube(expired air ventilation). Expired air ventilationproduces only just adequate inspired PO 2 and isvery tiring to perform. Clearly, the small humanforced expired volume cannot be expected to produceeffective ventilation in large animal species.In the absence of any apparatus, small animalscan be ventilated by blowing down the nostrilswhile the mouth is held closed, but the person performingthis must produce a seal with his or herlips around the animal’s nostrils. Another methodof artificial ventilation, i.e. intermittent pressureon the animal’s chest wall, may well be preferred.This is totally inadequate in providing ventilationfor any length of time but may keep the animalalive for a few minutes. Often, compressing thechest triggers a reflex spontaneous respiration,which is more effective than the attempt to ventilatein this manner.Stimulation of the animal in various ways mayresult in a reflex spontaneous breath. Such a reflexis the ‘chest deflation reflex’ described above.Movement of the tube in the trachea may alsomake the animal breathe. Most reflexes, however,are associated with painful input, the most obviousone being the respiratory response to thecommencement of surgery. Janssens et al. (1979)suggest the use of acupuncture to stimulaterespiration and recommends the placing of a needlein the nasal septum. Certainly in cats and dogsthat area is extremely sensitive, and its stimulationFIG.20.5 Ambu self-inflating bag for IPPV.If available,O 2 can be given to enrich the inspired air by delivering it throughthe small-bore plastic tubing.

516 SPECIAL ANAESTHESIAmay trigger reflex respiration, but in lightly anaesthetizedanimals it may also trigger cardiac arrest.In horses, stimulation of respiration by twistingthe ear appears more effective. It must be emphasizedthat adequate artificial respiration must becontinued whilst these attempts to stimulate respirationare being made.The common causes of apnoea are listed inTable 20.1. As treatment further to initial immediateartificial ventilation is dependent on the causeof failure, it is essential that the anaesthetist iscapable of making the diagnosis. The most commoncause of apnoea is respiratory obstruction or(commonly in horses) too great resistance withinthe patient breathing system. Once the resistance isremoved, spontaneous ventilation resumes. Oninduction and recovery from anaesthesia theanimal may hold its breath for a few seconds,particularly if an endotracheal tube is in place.Examination of the level of unconsciousnessshows very light anaesthesia and spontaneous respirationresumes rapidly once the endotrachealtube is removed.Central nervous depression is the most seriouscommon cause of apnoea under anaesthesia. It isparticularly serious as it may be accompanied bycirculatory inadequacies, so that the pulse shouldbe carefully monitored until recovery occurs.Depression may be caused by overdoses of anaestheticor analgesic agents or by cerebral hypoxia.The animal will be deeply unconscious but estimationof the depth can be very difficult for theTABLE 20.1 Causes of hypoxia in absence ofrespiratory obstructionCauses of hypoxaemia RemedyFailure of O 2 supplyAccumulation of N 2in breathing systemSticking of valves incircle systemsEnsure no disconnectionfrom the anaestheticsystem,no empty cylinderwhen supply is not frompipelineFlush breathing systemwith pure O 2 or freshanaesthetic gas mixtureCheck operation ofdirectional valves and ifnecessary replacebreathing systeminexperienced anaesthetist. Hypoxia and hypercapnia,from whatever cause, can lead to a jerkyrespiratory movements with jaw and limb movements,leading the unwary into thinking thatanaesthesia is light. Gasping respirations ofthe Cheyne-Stokes last-gasp type may precedeapnoea, and again the overall movement of theanimal which accompanies these may be misleading.Despite movement, there is, at this stage, notone in the muscles and all reflexes show thatanaesthesia is, in fact, deep.Drug overdoses are best treated by maintainingIPPV until the drug can be eliminated or its actionantagonized. However, reliance should never beplaced on the use of analeptic or antagonisticdrugs alone. Where volatile agents are implicatedthey are removed from the circulation by ventilation,and rapid recovery occurs. Parenteral agents,however, are more difficult to remove from the circulation.Where only a small dose of the anaesthetichas been given i.v. anaesthesia usuallylightens as redistribution of the agent occurs, butwhere a relative or gross overdose has beenadministered and no antagonists are available theonly method of increasing excretion may be toincrease the renal output by means of an i.v. infusionof dextrose, a balanced electrolyte solution ora diuretic such as frusemide (furosemide).Respiratory depression due to opioid drugsmay be counteracted by specific antagonists.Diprenorphine (Revivon) is the specific antagonistto etorphine but should not be used to treat etorphineintoxication in man, because it has agonistproperties. Naloxone (Narcan) is the drug in currentuse to antagonize the effect of all opioid agonistdrugs. Its long-acting derivative, naltrexone,has not been studied in veterinary anaesthesia butcould prove useful should a long-acting pureantagonist be required.Naloxone is most effective against the pure opioidagonists, and is less effective against partialagonists such as buprenorphine. It may be given topups delivered from a bitch given a morphine-likedrugs during labour. In dogs and cats the initial i.v.bolus of naloxone is 200 µg and this can be repeatedevery 2 to 3 mins, up to a total dose of 2 mg, untilthe desired response is obtained. Large doses, ordoses given too rapidly after each other, will resultin hypertension and arrhythmias.

ANAESTHETIC ACCIDENTS 517In horses naloxone has been used in i.v. bolusdoses of 0.005–0.02 mg/kg but its use in equineanaesthesia is still controversial because its efficacyas an adjunct has not been established and byantagonizing the horse’s endogenous opioids ahorse which is in pain may become restless.Overdoses of the α 2 adrenoceptor agonists canbe treated with antagonists such as yohimbine oratipamezole.The place of analeptic drugs in the treatment ofrespiratory failure during anaesthesia is debatableand it is undoubtedly true that the experiencedanaesthetist only rarely finds it necessary to recourseto them. Their duration of action is relativelyshort and that of a single dose may be too transientto restore complete respiratory activity. Thus it isnecessary to maintain a careful watch until signs ofrecovering consciousness are evident and shouldbreathing again become alarmingly shallow orcease, repeated doses should be given (or naltrexoneused with caution because its effects in veterinarypatients are currently uninvestigated).Doxapram hydrochloride (Dopram V) increasesthe respiratory minute volume by actingon the respiratory centre and, in general, dosesconsiderably larger than those used clinically mustbe used before general stimulation results in convulsions.Its use is safe at i.v. doses of 2 mg/kg in awide range of species. For clinical purposes an initialintravenous dose of 1 mg/kg is usuallyemployed and further doses given if required.Doxapram may also be used by the sublingualroute to stimulate respiration in the new-born.Despite the claims as to the specificity of the actionon the respiratory centre, in practice clinical dosesare usually found to decrease the level of unconsciousnessof the anaesthetized animal. Whilst thisis useful if apnoea is due to central depression, thisdrug must be used with care in large animals suchas horses, where the awakening may be violent.Normal levels of carbon dioxide in the bloodare necessary to maintain spontaneous respiration.However, the role of carbon dioxide in resuscitationin veterinary anaesthesia has been grosslyabused. Although a slight increase in carbondioxide stimulates respiration in the conscious animal,this reflex is considerably reduced in anaesthetizedindividuals. Under anaesthesia increasesin PaCO 2 cause increasing central nervous depression,which will itself eventually result in apnoea.Hypercapnia also sensitizes the heart to arrhythmiasand may precipitate cardiac arrest. In themajority of case apnoea is preceded by respiratoryinsufficiency and by the time that respiration ceases,hypercapnia already exists. The only circumstanceswhere CO 2 is required to stimulaterespiration is to treat hypocapnia following vigoroushyperventilation. If CO 2 is required to correcthypocapnia it is best added to the inspired gaseither from cylinders on the anaesthetic machine,or by increasing the deadspace of the patient circuit,as in this way it is possible to continue ventilationand prevent hypoxia from occurring. IPPVshould never be stopped to allow accumulation ofCO 2 in the breathing systemFailure to antagonize the effects of neuromuscularblocking drugs used during anaesthesia willresult in respiratory failure. Treatment consists ofthe continuation of IPPV until the effects of theblocker have worn off or been adequately antagonized.Pain in the postoperative period, particularlythat involved in movement of the thoracicand abdominal muscles, may cause hypoventilation.If opioid analgesics in limited doses are usedin such circumstances, the increased ventilationthrough pain relief is usually greater than any respiratorydepression as a direct result of the drug.Other causes of inadequate ventilation includepathological changes such as space-occupyinglesions of the lung or pleural cavity, and bleedinginto the substance of the lung.Normal PaCO 2 is essential for the maintenanceof normal tissue perfusion and hypocapnia leads toa decrease in cerebral blood flow. However, severehypocapnia does not occur in spontaneouslybreathing animals and the cerebral circulation isonly likely to be affected when IPPV is carried out insuch a way as to remove excessive amounts of CO 2 .Assuming ventilation to be adequate, thecommonest causes of hypoxaemia during generalanaesthesia include an inadequate supply of O 2to the breathing system from failure of supply(empty cylinder, disconnection), accumulationof nitrogen or nitrous oxide in a low-flow systemor faulty valves preventing the proper circulationof gases around the system (Table 20.1). Suchaccidents occur quite commonly, and should besuspected if an animal which has previously been

518 SPECIAL ANAESTHESIAwell becomes cyanotic despite an adequate respiratoryminute volume and an apparently adequatecirculation. Treatment consists of the administrationof O 2 , preferably utilizing a simple nonrebreathingpatient system. However, as long as ananimal is breathing spontaneously simply disconnectingit from the machine and allowing it tobreathe room air will usually provide the necessaryO 2 whilst the fault is being located.Diminished excretion of CO 2 from the lungsresults in respiratory acidosis. This state is commonlyseen when the total gas flow rate in a nonrebreathingsystem is too low, or when the sodalime in an absorber is exhausted. It also occurswhen the airway is obstructed, or when respiratorymovements are hampered by the position ofthe animal’s body on the bed or operating table.Usually, when the duration of anaesthesia is shortthere is insufficient time for severe acidosis todevelop, but long duration anaesthesia can lead toa serious fall in blood pH. Death occurs when thearterial blood pH falls below about 6.7.The signs of respiratory acidosis are not alwaysobvious. Hypoxaemia may have been avoided byan increase in the inspired O 2 so that the animal’smucous membranes remain pink and its pulseslow and of good volume (sometimes noted as a‘bounding pulse’). Although in normal animals anincrease in the PaCO 2 causes a frank increase in thetidal volume, in the anaesthetized animal this maynot occur. The ABP first rises, then returns to normaland finally falls. Circulatory failure, when itoccurs, is rapid and is due to heart failure. Whensevere respiratory acidosis has developed an animalmay collapse at the end of operation, forexcess CO 2 is rapidly excreted as respiratorydepression decreases with lightening of anaesthesiaand the circulatory reflexes are not activeenough to compensate for the rapid change inblood pH. The condition may be erroneously diagnosedas shock, but unlike shock is characterizedby a slow pulse and, usually, in otherwise fit animals,spontaneous recovery.CIRCULATORY FAILURECirculatory failure may be due to volume or primarycardiac insufficiency. The main concern isfailure of organ perfusion and ABP is often used asan assessment of this because modern technologyhas made pressure measurement easy in most animals.However, ABP does not necessarily correlatewith O 2 transport which is more related to bloodflow. Fortunately, the brain, heart and kidneys areprotected by autoregulation and blood flowremains constant in spite of large changes in ABP.Cerebral and coronary flow remain constant downto a MAP of 60 mmHg and renal blood flow doesnot fall until MAP falls below about 70 mmHg.Unexpected arterial hypotension during anaesthesiamust always be investigated and remedialmeasures taken to avoid serious consequences forthe animal.As is well known, ABP is determined by the cardiacoutput (CO) and the systemic vascular resistance(SVR). The CO is dependent on the strokevolume (SV) and heart rate (HR). Arterial hypotensionresults from a change of one or more of thesefactors and diagnosis and treatment of hypotensionmust be based on these fundamental considerations.INADEQUACY OF THE CIRCULATINGFLUID VOLUMEInadequacy of the circulating fluid volume to fillthe existing vascular bed may be due to anabsolute reduction in blood or body fluid volumes,or to an increase in vascular space as a result ofperipheral vasodilatation. In either case ifcompensatory mechanisms are impaired the effectis to decrease venous return and reduce preload.Reduction in preload decreases ventricular enddiastolicfilling with consequent decrease in SVand hence in CO. Hypovolaemia is one of themost common causes of hypotension duringanaesthesia, operating either alone or in conjunctionwith other aggravating factors. Venodilatationcauses reduced preload when compensatorymechanisms are impaired – for example whensympathetic venomotor tone is diminished byneuroaxis blockade.A very common cause of circulatory failureunder anaesthesia is surgical haemorrhage. Theremay be a sudden effusion of blood or, more commonly,an almost imperceptible loss over thecourse of a long operation. Unless blood loss is

ANAESTHETIC ACCIDENTS 519actually measured by swab weighing or someother technique, it is very difficult to estimate theamount of haemorrhage occurring and many surgeonsdo not appreciate the extent of the blood lossthey cause. Many of the drugs used in anaesthesiaabolish the normal physiological response tohaemorrhage and the tachycardia response seenin young, healthy animals may not occur in theelderly or sick.For practical clinical purposes all animals canbe considered to have a circulating blood volumeof about 88 ml/kg and when a loss of 10% of this(i.e. 8–9 ml/kg) has occurred it needs to bereplaced. Replacement of lost blood volume withnon-blood substances is often desirable if a moderatedegree of haemodilution can be tolerated. Anacceptable minimal level of haemoglobin seems tobe around 7 g/dl which offsets the reduced O 2content of the blood with reduced viscosity(Concensus Conference, 1988). However, the heartmust be capable of increasing CO to cope with tissuedemands and so animals suffering fromrestricted CO (e.g. aortic stenosis, valvular incompetence)must be maintained at a higher haemoglobinconcentration.The crystalloid v. colloid debate has often beenargued (e.g. Davies, 1989), but the best course isprobably to combine the two and replace extracellulardeficits with crystalloid solutions and largeblood losses with a colloid (albumin, polygeline orhydroxyethyl starch) and/or blood. Crystalloidsolutions, in a ratio of 3 ml to replace 1 ml of bloodloss result in euvolaemia after approximately1 hour because the crystalloids usually distributethemselves to the extracellular fluid after about20 minutes. Some tissue oedema occurs and thefinal equilibration results in less than one-quarterof the infused fluid remaining in the circulation;any diuresis evoked by the lower colloid pressurewill reduce this contribution still further. Thus, ananimal which has had its circulating fluid deficitreplaced adequately by crystalloids soon afterhaemorrhage may have a circulating fluid deficitand be suffering from arterial hypotension somehours later, despite having suffered no furtherhaemorrhage.Fluid deficits which may have arisen in the preoperativeperiod may lead to hypotension whenblood vessels are dilated by anaesthetic drugs.When the fluid loss is primarily an electrolyte loss,such as seen in vomiting dogs and cats or equinecolic cases, circulatory changes can be so severethat the animal appears shocked. However, incases where the deficit is primarily of water, itis more difficult to recognize and assess but unlessthis is done these animals will becomehypotensive following the administration ofvasodilator drugs, or following an apparentlysmall blood loss. Also, elderly animals do not toleratedegrees of haemorrhage which might notgive rise to concern in young, fit subjects. In allthese instances deficits should, whenever possible,be corrected before anaesthesia is induced, theonly exceptions being cases of intestinal obstructionwhere it is prudent to restore only the circulatoryfluid volume if the surgeon is not to beinconvenienced.Peripheral vasodilatation due to drugs administeredbefore and during anaesthesia, or, moreseriously, due to endotoxins may lead to circulatoryfailure but in their absence major changes inthe peripheral circulation can occur in response toautonomic reflex activity. For example, suddenhypotension during operation sometimes occurswithout warning in an animal whose cardiovascularand autonomic systems are healthy and wherethere has been but little loss of blood. The pulsebecomes imperceptible, respiration ceases and theveins (notably in the tongue) are dilated. Thepupils remain normal in size and this may bethe only indication that the heart has not stoppedbeating. This alarming reaction appears to be initiatedreflexly by certain surgical manipulations.For example, it may be seen during caesarian hysterotomiesin cattle and sheep when traction isexerted on the mesovarium or on the broad ligamentof the uterus. It may also be seen in dogsand cats when swabs or retractors are allowed topress upon the coeliac plexus, or when the stomachand liver are handled by the surgeon. Tractionon the eyeball also invokes parasympatheticmediated hypotension. When it arises the surgeonshould stop and not recommence operatinguntil recovery has occurred. These reactionsmay be avoided by gentle surgery and the anaesthetistshould note that gentle surgery is onlypossible when the patient’s muscles are adequatelyrelaxed.

520 SPECIAL ANAESTHESIASHOCKShock is best regarded as a caricature of physiologicalresponses to insults such as haemorrhage orprolonged decrease in circulating fluid volume. Inshock the outline of the body’s defensive featuresto these insults remains recognizable but it is exaggeratedand distorted to a degree that becomesboth absurd and damaging. The major factors inits initiation and maintenance are, therefore, as inarterial hypotension, decreased cardiac output,increased vascular resistance and decreased circulatingblood volume. Unless corrected, each ofthese feeds back directly, or through the autonomicnervous system, to worsen the state of the circulationuntil there is insufficient perfusion oftissues, i.e. the animal becomes ‘shocked’.Realization that the development of shock canbe prevented by the correction of the conditionsleading to it resulted in its being classified on aetiologicalgrounds:1. Hypovolaemic – due to haemorrhage (surgicalor traumatic), fluid loss (vomiting, diarrhoea).2. Vasculogenic – changes in systemic resistanceor venous capacitance due to sepsis, anaphylaxis,loss of vasomotor tone from central nervouslesions or anaesthetic agents.3. Cardiogenic – when the heart ceases to bean effective pump. This can result from suchthings as severe cardiac depression from drugs,arrhythmias, ruptured chorda tendineae, cardiactamponade, or failure of venous return due toaortocaval compression in tension pneumothorax.Ventricular strain may be caused by prolongedincrease in systemic vascular resistance and theheart muscle itself can be contused by thoracictrauma.This classification, while useful in recognition ofthe factors which has been responsible for shockdeveloping, have little bearing on the shock syndromeitself. The conditions giving rise to theshock state may be amenable to suitable prompttreatment but delay in initiating treatment, or failureto respond to treatment for some other reason,leads from a final common pathway to inevitabledeath. The actual processes which lead to thisirreversibility are complex and still the subject fordebate.It seems likely that irreversibility begins whenischaemic hypoxia changes to stagnant hypoxia incertain tissues, and prolonged vasoconstriction isthought to be a key factor. For instance, aftersevere haemorrhage, sympathetic activity and catecholaminesecretion produce vasoconstrictionand ischaemic hypoxia in the splanchnic bed, liverand kidneys. This regional vasoconstrictionenables the circulation to be maintained throughthe unconstricted cerebral and coronary vessels inspite of any reduction in CO. Transfusion at thisstage improves CO, relieves hypotension andmuch of the vasoconstriction, allowing tissue perfusionto be restored. If transfusion is delayed theconstricted arterioles become less and less responsiveto adrenaline (epinephrine), apparently due tothe accumulation of metabolites in the tissues. Thevenules retain their responsiveness to adrenalineand when the arterioles relax the capillariesbecome engorged as flow stagnates. Capillaryengorgement then raises the hydrostatic pressureso that fluid exudes from the capillary beds andoligaemia becomes more severe. Anoxic changesbecome serious, local haemorrhages appear andtransfusion is of no avail because it merelyengorges further the stagnant capillary bed. Thevenous return and CO continue to fall and theheart ceases to beat as the coronary flow isreduced.Changes in the abdominal viscera and sympatheticactivity are of importance in irreversibilityas is the endotoxin of Gram-negative bacilli. Thistoxin is absorbed from the damaged (anoxic)bowel, acts on the nervous system, produces arelentless abdominal sympathetic-induced vasoconstriction,and then it cannot be detoxicatedbecause of failure of the reticuloendothelialenzyme in the hypoxic spleen and liver. Endotoxinaction certainly has an important adrenergic componentbecause its lethal effect is countered byadrenolytic compounds and it potentiates thepressor responses to catecholamines.Vasopressors are much more likely to be harmfulthan beneficial in shocked animals. The onlymeasures which consistently reduce mortality arethose which increase blood volume or reducevasoconstriction and this has led to the suggestionthat vasodilators may have a place in the treatmentof shock. Although not to be used when the blood

ANAESTHETIC ACCIDENTS 521volume is already reduced and no substitute forcorrect fluid therapy it is claimed by some thatanti-adrenergic drugs and other methods ofinhibiting sympathetic activity improve survivalafter haemorrhage or trauma provided that furthertransfusion is given to cover the increasedcapacity of the vascular system. It is extremelydoubtful if the adrenal cortex plays any partalthough hydrocortisone (itself a vasodilator)given in massive doses of 50 mg/kg doses hasbeen used. Such massive doses are impracticablefor large animals, but phenylbutazone, in doses of15 mg/kg may be as effective as corticosteroids inthe treatment of endotoxic shock. Unfortunately,the best results are only obtained when thesedrugs are given before shock actually develops.Flunixin (1 mg/kg i.v.) may counter endotoxaemiain equine colic cases. During shock the endogenousopioid β endorphin is released from the pituitaryand it has been suggested that it may contribute tohypotension since this is alleviated by the administrationof naloxone. Although the use of naloxonemay be efficacious it may also restore pain sensitivitywhich is usually reduced in shock.The infusion of small volumes of hypertonicsaline may be beneficial in shocked animals. Thisapproach has been reviewed by Gasthuys (1994)and is quite distinct from volume replacementtherapy. Hypertonic solutions are easily preparedand are non-viscous, so that rapid infusion is possiblein spite of their high osmolality (for 7.2 % solution2400 mosm/litre). They cause movement offluid from the intracellular compartment to theinterstitium and the circulation and, consequently,this form of therapy must be followed by largequantities of isotonic solutions or other fluids suchas whole blood given i.v. The effects of i.v. hypertonicsaline solutions, sometimes mixed with colloidssuch as dextran, have been reported in cats (Muir& Sally, 1989), dogs (Mermel & Boyle, 1986; Rochaet al., 1990; Kein et al., 1991; Dupe et al., 1993), pigs(Maningas et al., 1986; Hellyer et al., 1993; ), sheep(Smith et al., 1985) and horses (Bertone et al., 1990;Dyson & Pascoe, 1990; Allen et al., 1991; Arden etal., 1991; Moon et al., 1991). Infusion of thesehypertonic solutions is not without its drawbacks.A potentially dangerous initial decrease in arterialblood pressure has been noted (Kein et al., 1991).Extreme neuronal dehydration and hypernatriaemiacan induce marked neurological dysfunction(Kleeman, 1979), i.v. hypertonic solutions cancause phlebitis and saturated (25%) or semi-saturated(15%) NaCl solutions produce haemolysis(Rocha et al., 1990). Care must be taken in theinterpretation of these reports since some relate toinfusions in normovolaemic as opposed to hypovolaemicor shocked animals.Much work has been done to establish thebest methods of estimating the state of the circulation.Undoubtedly the most useful determinationsare measurement of ABP, CVP, capillaryrefill time, the state of distension of peripheralveins and the urinary output. Treatment of establishedshock is seldom effective and it is, therefore,most important to intervene during the progressionof the conditions which lead to it. Early transfusionto restore the vascular volumes andexpeditious operation to arrest bleeding, removalof damaged tissue and, if necessary, fixation of brokenbones, will prevent irreversible shock fromdeveloping.DISTURBANCES OF CARDIAC RHYTHMTachycardia is usual in young animals, but inadults the pulse rate increases in shock or after theadministration of anticholinergics. It must be emphasized,too, that in animals under the influenceof neuromuscular blocking agents tachycardiamay indicate an insufficient depth of anaesthesia.Many factors determine whether an animal willdevelop arrhythmias during anaesthesia but somemay well have existed prior to anaesthesia. Holtermonitoring for 24 hours has demonstrated that alarge proportion of conscious asymptomatic animalsshow arrhythmias. Pre-existing arrhythmiasare usually benign and include sinus arrhythmiain healthy young animals and sinus bradycardia intrained athletic animals.If the anaesthetic agent is known to depress thefunctional capacity of the heart muscle it is naturalto assume that the direct action of the drug on themyocardium is the cause, but it is more probablethat serious arrhythmias are caused by the actionof autonomic nerves to the heart. The nervoussystem is often hyperactive immediately beforeanaesthesia, especially if the animal is frightened,and stimulation of sympathetic nerves to the heart

522 SPECIAL ANAESTHESIAmay cause ventricular extrasystoles (VES) or evenventricular fibrillation if the heart muscle is sensitizedby anaesthetic agents. CO 2 may accumulatein the body; this accumulation and/or mild degreesof hypoxia can cause stimulation of the sympatheticnervous system, so arrhythmias are commonwhen respiration is depressed or obstructed.Cardiac arrhythmias during anaesthesia arecommon and most are benign but in an emergencysituation the anaesthetist must know how to treatthose which have haemodynamic consequences orthose that are potentially dangerous. Althoughattempts have been made to grade arrhythmiassuch as VES this has not so far proved to be productivein terms of prognosis. During anaesthesiaa classification system based on an ECG may beuseful because ECG monitoring is now very commonin veterinary anaesthesia. Before contemplatingadministration of anti-arrhythmic drugs it isessential to consider the possibility that thearrhythmia might have an anaesthetic (hypercapnia,hypoxic) or surgical (haemorrhage, traction ontissues) cause. Cardiac arrhythmias only requirepharmacological treatment when:(a) they cannot be corrected by removing thesuspected cause,(b) they are haemodynamically relevant, and(c) when the type of arrhythmia is likely toprogress to a life-threatening condition.First, hypercapnia, hypoxia, arterial hypotension,inadequate anaesthesia and electrolyte disordersshould be corrected. Next, the use of potentiallyarrhythmogenic drugs should be terminated. Onlyif these treatments are ineffective should the use ofantiarrhythmic drugs be started. Currently, in medicalanaesthesia there is a growing concern aboutthe safety of many antiarrhythmic agents becausethese drugs have the potential to fail, increase theseverity of the arrhythmias or produce othercirculatory disturbances (Podrid, 1991).BradyarrhythmiasBradyarrhythmias are the result of an abnormalprolongation of the transmission of the electricalsignal to the ventricles or to an decreased automaticityof the sinoatrial node. They may result inreduced CO and very slow HR may lead to escapebeats. The optimum therapeutic approach is toincrease HR using atropine or glycopyrrolate. Ifbradycardia occurs in animals having epidural orspinal analgesia it is probable that i.v. ephedrine asa bolus, possibly followed by an infusion, is theregimen of choice.Supraventricular arrhythmiasSupraventricular extrasystoles originate at orabove the bundle of His so that the QRS complexof the ECG is narrow. They may represent thephysiological response to light anaesthesia, sympathomimeticstimulation, direct myocardial traumaor loss of circulating blood volume. Exclusionof an anaesthetic and/or surgical aetiology suggeststhat treatment with a Ca ++ channel blockersuch as verapamil may be indicated. However,verapamil may cause sinus bradycardia, sinusarrest, AV block, ventricular arrhythmias and evenventricular asystole. It also has a marked negativeinotropic effect and interacts with other drugs,principally digoxin and β blockers. While interactionof Ca ++ channel blockers with digoxin issynergistic, the combination with β blockersaggravates the negatively inotropic properties ofboth drugs and can lead to asystole.Atrial fibrillation is easily detected by theabsolute arrhythmia and if chronic before anaesthesiadoes not require any therapeutic interventionunless it causes very high heart rates. Digoxinor β blockers may be useful if atrial fibrillationappears unexpectedly during anaesthesia.Ventricular arrhythmiasPremature VES are very common and result inwide QRS complexes in the ECG because depolarizationspreads across the ventricle from cell to cellrather than through the His-Purkinje system.Common causes during anaesthesia includehypercapnia, electrolyte imbalance, direct myocardialtrauma and high levels of circulatingcatecholamines. Predisposing factors are medicationwith digitalis and ventricular dilatation.Isolated VES do not need specific antiarrhythmictreatment but if there is a significant rise in HR orventricular tachycardia occurs, therapy is essential.Lignocaine (lidocaine) is the drug of choice.

ANAESTHETIC ACCIDENTS 523Heart blockHeart block is due to the faulty transmission of theelectrical signal from the sinoatrial node to theventricles. Usually this occurs at the atrioventricularnode (AV block) or in the His bundle (left orright bundle branch blocks). First degree AV blockshows as an increased time interval between the Pwave of the ECG and the beginning of the QRScomplex. Second degree AV block is characterizedby the failure of some of the atrial depolarizationsto reach the ventricles, whilst in third degree AVblock none of the atrial depolarizations reach theventricles. Second degree AV blocks are classifiedas Mobitz I and Mobitz II blocks. In Mobitz Iblocks there is an increasing time between the Pwaves and the QRS complex until for a single atrialdepolarization a complete block occurs. This typeof heart block is known as the Wenckebach phenomenon.Mobitz II blocks have a constant PRinterval; however, there is a failure of some of theatrial depolarizations to reach the ventricles.Animals with Mobitz I or first degree block donot need special treatment but Mobitz II is muchmore serious and any animal showing this conditionbefore anaesthesia should be thoroughlyinvestigated and equipment for cardiac pacingshould be available if anaesthesia is needed.CARDIAC ARRESTThe causes of cardiac arrest, when the heart ceasesto function as a pump, are numerous and in anyone case it is likely that several factors may beimplicated but in the majority of cases hypoxiaand hypercapnia contribute significantly to itsoccurrence. Cardiac arrest of neurogenic origin,usually stimulation of the vagus nerves, is theexception to the general rule of multiple causation.Where the surgeon stimulates the vagus nerves,either directly or by initiating a reflex such as theoculocardiac, the heart may stop with no priorwarning. Such an arrest can only be detected bycontinuous palpation of the pulse or with an ECG,as the suddenness of the cessation of circulation asthe heart ceases to beat means that the tissues arewell oxygenated, the mucous membranes remainpink, and spontaneous respiration may continuefor 2 to 3 minutes until the respiratory centresbecome anoxic. By the time respiration has ceasedand the pupil has dilated, cerebral hypoxia makessuccessful resuscitation much more difficult. Thehorse and the cat are the species of animal mostsensitive to vagal arrest of the heart and theyshould be protected by the administration of anticholinergicsprior to surgery in the head and neckregions.Cessation of the cardiac pumping action mayfollow complete cardiac arrest (asystole), ventricularfibrillation, or electromechanical dissociation(EMD). Electromechanical dissociation is similarto asystole except that there is a regular electricalrhythm demonstrated on the ECG coupled withthe progressive failure of ejection of blood from theventricles. EMD occurs with overdose of anaestheticdrugs, hypovolaemia, acute cardiac decompensation,hypoxaemia or severe acidosis. Thesethree types of cardiac failure can be differentiatedby observation of the ECG and palpation of aperipheral pulse. Diagnosis of cardiac arrest mustbe rapid because during anaesthesia it may havebeen preceded by respiratory or circulatory insufficiencyso that the brain may already be hypoxicwhen the circulation ceases. Diagnosis is based onthe absence of a palpable peripheral pulse, absenceof heart sounds and ashen-coloured mucous membranescoupled with an absence of bleeding fromany surgical wound. These signs are closely followedby wide dilatation of the pupils and eitheragonal gasping or apnoea. Respiration will continueuntil the respiratory centres become anoxic.When any or all of these signs are observed thetraditional ABC protocol should be institutedwithout delay. A refers to airway and it is mostimportant to ensure that the airway is clear. Thepresence of an endotracheal tube does not necessarilymean that the airway is clear and itspatency and positioning should be checked.Endotracheal intubation is the best way of ensuringa patent airway in an animal which has notgot a tube in position. B refers to breathing andIPPV is usually needed to ensure an adequatealveolar gas exchange. A high inspired concentrationof O 2 is most desirable. C indicates attentionto the circulation which in this situation meansrepetitive compression of the heart or intact chest.Conservative treatment is not only uselessbut also wastes valuable time. The only way of

524 SPECIAL ANAESTHESIArestoring an effective circulation is the immediateinstitution of resuscitative measures. Once aneffective circulation with O 2 delivery to the tissueshas been established, the immediate danger to thelife of the animal is over.It is always worth trying the effect of a manualthump over the precordial region of the chestbecause this sometimes results in resumption ofcardiac contractions and does not delay the institutionof other measures. There are two ways ofattempting to provide an effective circulation tothe brain and myocardium. One, and first thatshould be tried, is compression of the intact chest;the second is direct compression of the surgicallyexposed heart. The use of cardiac stimulant drugsshould not be considered until the myocardium isonce more well oxygenated and, therefore, theyhave no place in the initial treatment.There should be a simple, set routine for thetreatment of circulatory arrest, which is known toall those working in the theatre, recovery unit orelsewhere. Table 20.2 sets out such a routine.TABLE 20.2 Cardiac resuscitation routineStage 1: Establishment of an artificial circulation1. Notify the surgeon and note the time2. Clear and maintain the airway3. Carry out IPPV (if possible with O 2 )4. External compression of the chest;ifineffective perform internal cardiacmassage5. Where possible,place and maintain inhead-down positionStage 2: Infuse fluid to restore or maintaincirculating volumeThis may be left until after Stage 3Stage 3: Improve condition of the heartAdminister adrenaline (epinephrine) inappropriate doses for the type of animalconcerned,preferably i.v.but if impossibleinto the tracheobronchial tree or directlyinto the left ventricleStage 4: Post-resuscitation1. Continue IPPV2. Counteract acidosis by pulmonaryhyperventilation3. Prevent cerebral oedema –corticosteroids,diuretics4. Continue circulatory support withadrenaline infusion into a central vein(dopamine,dobutamine can be used)As soon as circulatory arrest is detected theadministration of any anaesthetic must bestopped; a clear airway must be ensured and IPPVpreferably with pure O 2 instituted. At the sametime external chest compression (see below)should be started to improve the venous return tothe heart; whenever possible the animal shouldbe placed in a head down position. The effectivenessof chest compression may be judgedby the presence of a palpable carotid pulse causedby each compression and a reduction in the diameterof the pupil. If chest compression does notprove to be effective, then direct cardiac compressionof the surgically exposed heart must beconsidered.Effective external chest compression is possiblein most animals although it is probable that exceptin cats and similar small animals this will not compressthe heart itself. In cats and small dogs thechest walls over the region of the heart are compressedbetween the fingers and thumb of onehand. Larger animals are quickly placed on theirside on a hard, unyielding surface. The upperchest wall over the region of the heart is thenforced inward and allowed to recoil outwards,movement of the lower chest being restricted bythe hard surface on which the animal is lying. It isan advantage if the lower chest wall can be supported.In dogs and other small animals pressureon the uppermost chest wall with the hand is adequate,but in adult horses and cattle or similarlysized animal the knee or foot is applied to the chestwall over the region of the heart. The rate of compressionshould be about 60 compressions/min indogs, or 30/min in adult horses and cattle. Aremarkably effective circulation can be maintained(Fig. 20.6); respiratory movements may return,although they are usually inadequate to provideproper gaseous exchange in the lungs and IPPVshould not be stopped. The size of the pupilsshould decrease and the level of unconsciousnessshould lighten. The authors have seen a horse startto recover consciousness and to move its limbswhile thoracic compression was being performed.The way in which external chest compressionproduces blood flow in the body is debated. It wasinitially thought that when the chest was compressedthe heart was squeezed, so ejecting bloodinto the aorta. This may be so in small animals,

ANAESTHETIC ACCIDENTS 525FIG.20.6 Tracing showing carotid arterial pressureproduced by chest compressions in a dog suffering fromcoarse ventricular fibrillation.Provided the myocardium iswell oxygenated electrical defibrillation should restorespontaneous heart beat.particularly in cats or animals of a similar size andin narrow chested dogs, where it is usually possibleto feel the resistance to compression of theventricles through the compliant chest wall, butthis is unlikely to occur in larger animals. It seemsmore likely that another mechanism is alsoinvolved in the latter, and this may be the onlymechanism in larger animals. External chest compressioninduces intrathoracic pressure changes,pushing blood in a retrograde and forward fashion,but due to the presence of valves and collapseof veins, retrograde flow is stopped early on andblood is allowed to flow into the aorta. The flow ofblood through the lungs is thought to be due to acascade effect between the right and left sides ofthe heart but emptying of the blood from the lungsis also caused by pulmonary ventilation. Whateverthe reason for forward blood flow through theaorta it appears that external chest compressionmay not be very protective of the brain as if this isperformed for more than 3–4 min it is oftenfollowed by significant neurological deficits,possibly because the induced cerebral blood flowsupplies glucose but insufficient O 2 for its metabolism,so that anaerobic metabolism produces largeamounts of lactate and other products. As againstthis, if resuscitation is delayed for more than 3 to4 min the glucose substrate will become exhausted.Because the technique of external chest compressionis often not followed by a satisfactory outcomeseveral procedures have been advocated forimproving the pulmonary pump mechanism. Thefirst is to bind the abdomen with an Esmarchbandage to limit the caudal displacement of thediaphragm and hence increase the intrathoracicpressure during chest compression. The second isto alternate compression of the chest and abdomenbut this gives rise to risk of damage of the liver. Athird suggestion is to limit the collapse of the lungsduring compression by ventilating with IPPV asthe chest compression is applied. None of thesehas been shown to improve survival in veterinaryclinical practice.Cardiac fibrillation may be present as the causeof circulatory arrest or may be precipitated in anasystolic heart by the effects of drugs or even chestcompression. The best and most specific treatmentis to pass an electric shock through the myocardiumso that when the contraction it causes passesoff the whole muscle remains in a relaxed state ofasystole: following this it is hoped that normalcontractions will start spontaneously. Electricaldefibrillation attempts will do no harm to a heartthat is in asystole and may even induce it to startbeating, so applying a shock, or shocks, is nowregarded as one of the first measures to be undertakenin cases of cardiac failure during anaesthesia.Compact and relatively inexpensive apparatusis available for external defibrillation (electrodesplaced on the chest wall (Fig. 20.7) and internal useelectrodes placed on the myocardium itself). Allthese pieces of apparatus are designed for manand they are suitable for use in small animals buttheir output may be inadequate for larger animaluse unless repeated shocks are given. This may notbe so much of a problem in horses for ventricularfibrillation, when it does occur, tends to be veryshort livedFor defibrillation through the intact chest wall,with good electrical contact assured by conductinggel, shocks of about 1 J are necessary in cats, from1 to 8 J in dogs and 400 J (repeated shocks at 15 secondintervals) in horses and cattle. When the electrodesare applied over saline-soaked padsdirectly on the myocardium shocks of about 0.2J/kg appear to be effective in most cases. Attemptsat electrical defibrillation are much more likely tobe effective if the myocardium is showing coarsefibrillation and is well oxygenated before theshock is applied.

526 SPECIAL ANAESTHESIAFIG.20.7 Defibrillator for external use.For reasons ofsafety in use both the electrodes have switches in theirinsulated handles.These switches need to be pressedsimultaneously to deliver the shock.This particular modelof defibrillator has its own monitor ECG.If an effective circulation cannot be producedby external chest compression coupled with electricaldefibrillation, the heart must be exposed by athoracotomy incision. Obviously, facilities forIPPV must be available before this can be done. Notime should be lost in ‘scrubbing up’ or in preparingthe operation site before making an intercostalincision and when the heart is exposed the ventriclesmust be squeezed rhythmically. The squeezingshould be carried out with a motion from theapex towards the base of the heart (rather like thereverse of hand-milking of a cow’s teat). The rateof compression should not be too rapid for thechambers of the heart need to have time to fillbetween compressions and a slight head-downinclination of the body assists this. In every casecare must be taken to avoid rupture of the heart bythe fingertips. In small animals the ventricles canbe compressed by the grasp of one hand but inlarger animals both hands must be used. The effectivenessof the circulation produced by this may begauged by the maintenance of a small pupil sizeand the presence of a palpable carotid pulse whenthe ventricles are squeezed.Often, when the chest is opened because externalchest compression is judged to be ineffective itis found that venous return is not sufficient to fillthe heart between compressions, indicating thatthe reason for cardiac failure was hypovolaemia,and in these circumstances direct cardiac compressionis also ineffective until a rapid i.v. infusion hascorrected the deficit in the blood volume.Once an apparently satisfactory artificial circulationhas been established there is no longer anynecessity for haste and there is time for a consideredapproach. Ideally, as soon as the primaryresuscitative measures have been commencedintravenous fluids should be given to expand thecirculatory volume. Where cardiac failure is ofunknown origin, 5% dextrose is used, but if haemorrhagecaused the problem, then a plasma volumeexpander such as a gelatine or starch solutionis to be preferred. However, in veterinary anaesthesiathere may be no venous line in place and sothis may be a counsel of perfection as venepunctureis usually very difficult at this time.Attempts to set up an intravenous infusion shouldnot interfere with resuscitation and, if venepunctureis impossible, placement of an intravenousline should be deferred until the situationis more stable.In the past bicarbonate was often administeredat this stage to counteract the acidosis whichoccurs as a result of hypoxia. However, today theconsensus of opinion appears to be that acidosisshould be counteracted by deliberate hyperventilationof the lungs. This avoids the risk of alkalosisdue to too much bicarbonate provoking arrhythmiasand resulting in intractable ventricular fibrillation.Although various substances such ascalcium chloride were formerly used, adrenaline(epinephrine) is now generally considered to bethe cardiac stimulant of choice. Treatment withadrenaline will do no further harm to a fibrillatingheart and indeed it may even be successful inrestoring a normal rhythm. It acts on α and β sympatheticreceptors thus not only stimulating themyocardium but also increasing the peripheralresistance and hence improving coronary perfusion.An initial dose of 10 µg/kg should be givenand as the action of this drug is short-lived furtherdoses are often needed every 3–4 min or an i.v. infusionmay be used (1:50 000 in Hartmann’s solution).If i.v. injection cannot be achieved, the initialdose may be given through a catheter passedthrough the endotracheal tube and wedged in abronchus. Attempts to inject directly into the ventriclesare inadvisable since coronary vessels maybe damaged.

ANAESTHETIC ACCIDENTS 527When an electrical defibrillator is not availablelignocaine hydrochloride in doses of 1 mg/kg maybe injected i.v. and massage continued to force itinto the coronary vessels. At this dose lignocaine(lidocaine) depresses cardiac excitability and prolongsthe refractory period of heart muscle, but italso decreases myocardial contractility. Althoughworth trying, experience has shown that its use isonly seldom successful in stopping ventricularfibrillation.Ventilation of the lungs with O 2 should be continueduntil all evidence of circulatory failure hasvanished. At this stage, there will be a metabolicacidosis due to the products of anaerobic metabolismin the peripheral tissues being returned to thecirculation.Bradycardia with heart block is common followingrestoration of the circulation after prolongedmyocardial hypoxia. This bradycardia isusually refractory to treatment with atropine andmany cases do not respond to sympathomimeticdrugs so electrical pacing of the heart may offer theonly hope of successful treatment. However, it isalways worth trying the effects of 1 in 50 000adrenaline before considering electrical pacing.External pacing of the heart uses voltages of100–150 V and frequently leads to skin burns at thesite of the electrodes, so internal pacing using 3–5 Vfrom a wire electrode passed from the jugular veininto the right ventricular chamber is to be muchpreferred.If, in spite of transfusion to a satisfactory rightatrial filling pressure as shown by a CVP of 6 to7 mmHg, and distension of peripheral veins, thespontaneous heart beat is incapable of maintainingan adequate CO and ABP, inotropic supportshould be given. Dopamine is claimed to have theadvantage of improving renal blood flow by stimulationof renal receptors and is a relatively safeinotropic drug. Dobutamine, on the other hand, isa pure β 1 agonist which is said to work primarilyby improving stroke volume rather than byincreasing the heart rate. Isoprenaline, another βagonist, also improves cardiac output but causesa marked tachycardia. Adrenaline (1:50 000in Hartmann’s solution) given at a rate of0.02ml/kg/min or as necessary to maintain a systolicpressure of about 120 mmHg is, however, theinotropic drug of choice. Once inotropic supporthas been started it cannot be withdrawn abruptlyand careful weaning is necessary, usually over aperiod of several hours.Cerebral oedema is not uncommon due tohypoxia during the circulatory arrest and animalswhich have apparently been successfully resuscitatedmay lapse into unconsciousness from thisseveral hours later. To limit this oedema, the resuscitatedanimal should be given large i.v. doses ofcorticosteroids (e.g. 1 mg/kg methylprednisolone,every 6 hours for four doses) and diuretics such asfrusemide (which also decreases CSF productionand enhances its clearance).The greater the time elapsing before restorationof adequate spontaneous circulation, the poorerthe prognosis. The heart is more resistant to theeffects of hypoxia than is the brain so that if theheart does not readily respond to resuscitativemeasures it is likely that cerebral function will beso compromised as to make normal life impossible.Usually, it is unrewarding to attempt resuscitationof an animal that has had no effective circulationfor more than 5 minutes unless it was veryhypothermic when circulatory arrest occurred.Following successful restoration of the heartbeat by open chest cardiac massage the beatshould be observed for several minutes before thechest is closed. This time is used to secure anybleeding points. In spite of the lack of sterile precautionsin opening the chest and massaging theheart, sepsis is rare in animals which recover.EMERGENCY RESUSCITATION EQUIPMENTIn the operating room, most animals are routinelyintubated and facilities for airway and ventilationcontrol are readily available on the anaestheticmachine. An emergency trolley for use in the operatingroom should carry syringes and needlesof all commonly used sizes, a fluid administrationset and i.v. cannulae, several bags of infusionfluids, and drugs – appropriate for the treatmentof cardiac arrest in the various species of animalalready – drawn up into labelled, capped syringes,with the doses, in terms of volumes of solution,required for the size of animal written on thesyringe labels (in an emergency there is little timeto calculate the doses from those given on datasheets in mg/kg or the dilutions needed).

528 SPECIAL ANAESTHESIAWhenever possible the kit should include a cardiacdefibrillator and electrocardioscope. In general,drugs on the emergency trolley should be kept to aminimum, e.g. lignocaine, atropine, and naloxone.Other drugs such as vasopressors, cardiac stimulants,β blockers and diuretics are best kept on asecond shelf or in a drawer of the trolley so thatidentification problems do not arise at the time ofgreatest emergency.Because the success of resuscitation dependsgreatly on the speed and efficiency with which it isapplied it is advisable to have a basic resuscitationkit wherever animals are recovering from anaesthesia.The actual requirements depend on thespecies of animal concerned and on the particularcircumstances. Airway problems are likely tobe important and the kit should contain endotrachealtubes, laryngoscope, and a self-inflatingbag, (e.g. an Ambu bag, Fig.20.5). Some drugssuch as adrenaline and naloxone should be includedwith a suitable range of needles and syringes,and a bag of intravenous infusion fluidtogether with an administration set may bethought worthwhile.HYPOTHERMIA AND HYPERTHERMIAFIG.20.8 Circulating pump and water blanket for smallanimal patients.Although body temperature may rise during anaesthesia,hypothermia is much more commonlyencountered. Whenever return to consciousness isunexpectedly delayed hypothermia should be suspected.Waterman (1981) reviewed the causes,effects and prevention of hypothermia. Basically,the causes consist of a reduction in heat productionby the animal, usually coupled with an increasedheat loss. It is very difficult to influence production,but Waterman recommends several methods ofreducing heat loss. She suggests that care should betaken not to wet the animal excessively to reduceevaporative heat losses, placing the animal on awarm surface, preferably a water blanket heated to38 °C (Fig 20.8) and keeping the drapes over theanimal as dry as possible. Ambient room temperatureshould be kept high but not so high as to makefor impossible working conditions (20 to 22 °C isusually satisfactory). Respiratory heat losses areincreased when the animal breathes cold dry gasfrom non-rebreathing systems. Although such lossesare reduced by the use of the use of rebreathingcircuits, the use of these systems may entail excessiveresistance to respiration for small animalswhere heat loss is particularly significant. In thesesmall animals a suitable humidifier can be used toreduce heat losses (Dodman & Brito-Babapulle,1979). Particularly in small animals, all infused fluidsshould be heated to 38 °C using an electric fluidwarmer or by letting them flow through a coil oftubing immersed in a bath of warm water.With the smallest of animals hypothermia is avery serious problem, but it may be the cause ofslow recovery from anaesthesia in any cat, dog,foal, calf or lamb. Should it occur it is easily treatedby warming the patient, but many hypothermicanimals will shiver violently in the recovery periodand, as well as increasing heat production thiscauses a considerable increase in oxygen consumption,so that the administration of O 2 shouldbe considered in addition to the provision ofwarmth.Hyperthermia, or heat stroke, is an unusualcomplication of anaesthesia. It may, however,occur in a warm environment if small animals areanaesthetized using a low-flow system in a highenvironmental temperature. Systems with CO 2absorption prevent the loss of heat by panting andevaporation from the respiratory tract. Treatmentis to change the anaesthetic system to one whichdelivers cold, dry gases, to cool the animal withice-packs and cold water applications and, if nec-

ANAESTHETIC ACCIDENTS 529essary, to administer drugs producing vasodilatation.Active treatment should be discontinuedwhen the body temperature is still 1 °C above normalor it may overshoot in a most disconcertingway. Hyperthermia will, of course, also occur inpathological sensitivity reactions such as porcinemalignant hyperthermia.ANAPHYLAXIS ANDANAPHYLACTOID REACTIONSAn adverse drug reaction is the occurrence of anydrug effect not of therapeutic, diagnostic or prophylacticbenefit to the animal. Anaphylaxis (ananaphylactic reaction) is an exaggerated responseto a substance to which the individual has becomesensitized, in which histamine, serotonin and othervasoactive substances are released from basophilsand mast cells in response to an IgE mediated reaction.An anaphylactoid reaction is clinically indistinguishablefrom anaphylaxis but is not mediatedby sensitizing IgE antibody. Previous exposure isneeded for anaphylaxis but not for an anaphylactoidreaction. Whether a reaction is designatedanaphylactic or anaphylactoid may depend onhow it has been investigated and how the resultsof tests are interpreted. Recurrence of symptomscan occur up to 8 hours after the initial manifestation,apparently due to recruitment of inflammatorycells such as eosinophils.Clinical manifestations of anaphylaxis canappear within seconds of exposure to the antigenTABLE 20.3 Based on booklet of the Associationof Anaesthetists of Great Britain and Irelandand British Society of Allergy and ClinicalImmunology (1995) Suspected AnaphylacticReactions Associated with Anaesthesia (revisededition)Type A anaphylaxisDose relatedExtension ofpharmacologicalresponseCommonType B anaphylaxisNot dose related – may beprecipitated by a very smalldose.More severe onre-exposureSigns unlike normalpharmacological response.Typical of drug allergyUncommonbut may be delayed for 30 to 60 min. The diagnosisis based solely on clinical grounds because there isno quick diagnostic test. Vasodilatation togetherwith an increase in vascular permeability producesoedema, hypotension and decreased tissueperfusion. Cardiac arrest can occur with but littlewarning. Laryngeal oedema and bronchospasmmay interfere with pulmonary ventilation. Facialoedema may occur and periorbital oedema hasbeen seen in horses and dogs, while cattle haveshown, in addition, multiple cutaneous uticarialplaques.Treatment involves the ‘ABC’ of resuscitation(p. 517). High concentrations of O 2 should beadministered and any IPPV support neededshould be given with prolonged expiratory timesto allow the lungs to empty in spite of the presenceof bronchospasm. The drug of choice is adrenaline(epinephrine), preferably given i.v. in doses of 1µg/kg/min but an i.m. injection of 10 µg/kg is initiallyprobably as good. Further treatment to supportthe blood pressure entails the i.v. infusion ofadrenaline 0.5 µg/kg/min, or as needed. All animalswith anaphylaxis should receive steroids andantihistamines (e.g. 1 mg/kg of methylprednisolone,promethazine 0.2 to 1.0mg/kg) becausealthough these drugs are not helpful in the immediatemanagement of the condition they mayreduce the severity of the late-phase response.There is a synergistic effect between adrenalineand the infusion of i.v. fluids given rapidly toexpand the intravascular volume.When an anaphylactic episode has been encounteredduring anaesthesia the animal’s ownershould be notified and given a written statementto present to any veterinarian contemplatinganaesthetizing the animal at a future date. Thisstatement should, where possible, indicate the suspectedallergen, or at least specify all the agentsused in the procedure when the reaction occurred.OTHER CAUSES OF ANAESTHETICACCIDENTPOSTUREAll anaesthetized animals should be movedwith great care to ensure that they are adequately

530 SPECIAL ANAESTHESIAsupported at all times. In small animals, mishandlingof the patient can, for example, result in theprotrusion of a calcified intervertebral disc. Thearthritic animal, if mishandled, may be in considerablepain for several days following anaesthesiafor purposes unconnected with joint problems.The problems in large animals may be even moreserious. If the hindlegs of horses and cattle areabducted during anaesthesia obturator paralysismay result in the animal being unable to regain thestanding position on recovery. The facial nerve ofthe horse is easily damaged by pressure on the facefrom the buckle of a head-collar or the edge of anoperating table. Ischaemic muscle damage inhorses has already been considered and theseanimals appear to suffer intense pain from thiscondition.The position during operation must always begiven careful consideration; pressure points mayneed to be protected by suitable padding, andlimbs should never be held abducted but alwaysrestrained forward or backwards to avoid nervedamage. The cornea can be protected by closingthe eyelids, if necessary with adhesive bandage,but because this precludes observation of the eyeballposition, and elicitation of the lid or cornealreflexes, it is always better to keep the level ofanaesthesia light enough for the eyelids to remainopen during general anaesthesia and tear formationto be preserved.ANAESTHETIC EXPLOSIONS AND FIRESProbably the main cause of explosions in operatingrooms used to be static electricity coupled withthe use of explosive inhalational agents. Today,with the almost universal use of non-inflammable,non-explosive agents, fires in the operating areasare generally associated with the use of diathermyand alcoholic skin disinfectants by surgeons. Itmust be remembered that many substances willburn in oxygen and, therefore, that no oil or greasemust be used on O 2 cylinder connections; moreover,N 2 O will support combustion.INTRAVENOUS INJECTIONSThe commonest mishap is accidental injection ofan irritant solution such as guaiphenesin orthiopentone into perivascular tissues. When thishappens the injected irritant solution should bediluted by immediate injection of a large volumeof saline into the site. Hyaluronidase may be dissolvedin the saline and this enzyme will hastenabsorption of the irritant drug. No other treatmentis required. It is often suggested that a local analgesicsuch as lignocaine (lidocaine) should beinjected into the site of extravasation because thesesolutions have a low pH that counteracts the highpH of solutions such as thiopentone but it is likelythat any beneficial effect noted is due to thevasodilatation they produce. Solutions of themcontaining vasoconstrictors such as adrenaline donot have any beneficial effect.Venous thrombosis is common in small animalsafter the i.v. injection of 5% thiopental but, as it doesnot appear for 5 to 10 days, it may be missed unlessthe anaesthetist has occasion to give another injectionafter that time. Whenever possible, thiopentalshould be used as a 2.5% or even more dilute solution,and care should be taken that venous flow isnot obstructed when the injection is made. Venousobstruction caused by acute flexion of the elbow orunnatural position of the limbs will result in i.v. irritantsolutions being retained in the vein and thismay give rise to thrombosis. In horses similar considerationsapply to guaiphenesin and care shouldbe taken to ensure that it is not retained in the jugularvein due to the obstruction of this vein.Permanent obliteration of vessels resultsfrom repeated, clumsy attempts at venepuncture,the use of unnecessarily large needles or cannulaeand allowing large haematomata to form at the siteof venepuncture. In animals superficial veinsare not too plentiful and their preservation isimportant.LOCAL ANALGESIAGenerally manifest toxic reactions to analgesicdrugs arise when the drugs are absorbed into thecirculation at a greater rate than that at which theycan be broken down by the body. Rapid absorptionoccurs from any hyperaemic or inflamed tissueand the rate of absorption is increased by the use ofsolutions which contain spreading agents such ashyaluronidase. Accidental intravascular injectionmay occur even though no blood can be aspirated

ANAESTHETIC ACCIDENTS 531into the syringe before injection. The rate ofabsorption is decreased by the addition of vasoconstrictordrugs to the system.Local analgesics both stimulate and depress theactivity of the central nervous system. They havethe same membrane stabilizing effect on the heartand nervous tissue of the brain as on the peripheralnervous system. Overt symptoms of centralnervous system toxicity appear before the cardiovasculareffects become apparent. In large doseslocal analgesics affect cardiac conduction and contractility.ECG changes include an increase in PRinterval, atrioventricular dissociation and prolongationof the QRS complex. As plasma concentrationsincrease, pacemaker activity decreases,causing sinus bradycardia and, eventually, asystole.Often, toxic effects manifested by stimulationwill vary according to the region of the brainaffected. Cortical stimulation produces generalizedclonic convulsions, while stimulatoryeffects in the medulla cause an increase in the rateand depth of respiration, tachycardia and vomitingin those animals where this is possible. Typicalgeneral anaesthesia with respiratory and vasomotordepression usually follows. It is uncertainwhether death is due to cardiac or to respiratoryfailure, but it seems probable that i.v. injection ofthe agent causes sudden primary cardiac failure,while rapid absorption from tissues results indepression of the central nervous system and respiratoryfailure.The minimum lethal doses of the various localanalgesic agents for the different species of animalencountered in veterinary practice are largelyunknown. It is probable that insufficient attentionis given to the quantities of local analgesicsinjected in clinical veterinary anaesthesia. In everycase where collapse has occurred after the use of alocal analgesics IPPV should be commencedat once. Analeptic drugs should be withheld sincethey increase the O 2 requirements of the brain.Convulsions should be controlled by the i.v.injection of hypnotic doses of short or ultra- shortacting barbiturates and it is probable that thiopentalwill be the drug most readily available for thispurpose. Hypotension due to peripheral or centralvasomotor failure should be treated by the intravenousinjection of vasopressor drugs. Primarycardiac failure must be treated by chest compressionor direct cardiac massage (p. 518).EPIDURAL ANALGESIADrugs used to produce spinal analgesia can causea reaction affecting both the meninges and spinalnerves. Clinical signs resulting from damageto nerves appear rather rapidly after the effects ofthe nerve block should have passed off. The regionof the spinal cord subjected to the greatestconcentration of the drug shows the mostmarked pathological changes. Where the mainlesion is in the meninges clinical signs appear laterand reaction to the drug takes the form of an asepticmeningitis which may be mild or severe. Thesecomplications do not appear to be due to faultytechnique. Injection of the drug into the substanceof the spinal cord produces a severe myelitisand neuritis. Damage to the CNS is rarelyreversible and management requires prevention,not treatment.In man, post lumbar puncture headache is awell recognized complication and it has beenobserved that sheep subjected to spinal analgesiabehave in a manner suggesting they too sufferfrom headache. The headache is believed to be dueto low cerebrospinal fluid pressure caused by leakageof the fluid through the needle puncture in thedura mater. It does not occur after epidural blocks.Infection of the epidural space is fortunatelyrare but has been reported after caudal epiduralblock in cattle. The prognosis appears to be betterin those cases in which the infection is withinthe dura for it usually remains localized. Strictaseptic precautions should be employed whenevera spinal or epidural block is attempted.The rapid injection of a large volume of fluidinto the epidural space may cause arching of theback and opisthotonus. This reaction is presumablydue to a rapid increase in pressure in theepidural space and is usually of short duration. Notreatment is required.DANGERS TO THE ANAESTHETISTModern drugs are very potent and it is mostimportant that the anaesthetist does not come

532 SPECIAL ANAESTHESIAunder their influence. Drugs such as ketamine, theα 2 adrenoceptor agonists or their antagonists,which are normally injected into animals, may beabsorbed through the human skin or mucousmembranes and when handling them appropriatecare should be taken. Splashing onto the skin,the lips or eyes should be avoided, but if it doesoccur, immediate, copious irrigation of thesite with water is essential to avoid their effects.Gloves should be worn when handling some ofthe α 2 adrenoceptor agonists or their antagonistsand etorphine. Syringes and needle cases shouldnever be held in the mouth (this appears to be acommon practice under field conditions but cannotbe excused) because their exterior surfaces mayhave been contaminated with the drug while it wasbeing drawn up and air expelled from the syringe.Dangers of exposure of the anaesthetist andoperating room personnel to inhalation agentshave already been discussed. In the UK the Departmentof Health (1976) has advised that reasonablemeasures should be taken to reduce the risk ofserious contamination of the atmosphere withvolatile substances. Similar, but much more elaboraterecommendations, have been made in theUSA by the National Institute of OccupationalSafety and Health (1977).Sensible, simple measures which can be takenin veterinary practice to reduce atmospheric pollutionin operating rooms include:1. Vaporizers should always be filled outsidethe operating room and proper filling apparatusshould be used, but if this is not possible funnelscan reduce the risk of spillage of the liquidanaesthetic.2. Vaporizers should be turned off when not inuse.3. Anaesthetic agents should not be used forcleaning purposes (especially of clothes!) or skindisinfection.4. Whenever it is safe and convenient to do so,low flow systems of administration should be used.5. Scavenging of waste gases and vapoursshould be encouraged.6. Whenever practicable, endotracheal intubationshould be practised to prevent undueatmospheric pollution as may occur from the useof ill-fitting face-masks.7. All breathing circuits, especially thosedesigned for low-flow use, should be checked,regularly, for leaks.There are many scavenging devices suitable forveterinary purposes but care must be taken toensure that their use does not have an adverseeffect on the patient. It must also be rememberedthat activated charcoal containers used to removevapours such as halothane from the exhaled gasesdo not absorb N 2 O.REFERENCESAllen, A., Schertel, E., Muir, W.W. and Valentine, A.(1991) Hypertonic saline/dextran resuscitation ofdogs with experimentally induced gastric dilatationvolvulusshock. American Journal of Veterinary Research52: 92–96.Arden, W.A., Reisdorff, E., Loeffler, B.S., Stick, J.A., andWalters, D. (1991) Effect of hypertonic-hyperoncoticfluid resuscitation on cardiopulmonary functionduring colon torsion shock in ponies. VeterinarySurgery 20: 329–333.Bertone, J.J., Gossett, K.A., Shoemaker, K.E.; Bertone,A.l. and Schneiter, H.L. (1990) Effect ofhypertonic vs. isotonic saline solution onresponses to sublethal E. coli endotoxemia inhorses.American Journal of Veterinary Research51: 999–1007.Concensus Conference (1988) Perioperative red bloodcell transfusion. Journal of the American MedicalAssociation 260: 2700–2703.Davies, M.J. (1989) Crystalloid or colloid: does it matter?Journal of Clinical Anesthesia 1: 464–471.Department of Health (1976) HC(76)38 or SHHD/DS(76). 65. London: DHSS.Dodman, N.H. and Brito-Babapulle, L.A. (1979) The roleof humidification in anaesthesia. Proceedings of theAssociation of Veterinary Anaesthetists of Great Britainand Ireland 8: 141–147.Dupe, R. Bywater, R.J. and Goddard, M. (1993) Ahypertonic infusion in the treatment of experimentalshock in calves and clinical shock in dogs and cats.Veterinary Record 133: 585–590.Dyson, D.H. and Pascoe, P.J. (1990) Influence ofpreinduction methoxamine, lactated Ringersolution, of hypertonic saline solution infusionor postinduction dobutamine infusion onanesthetic-induced hypotension in horses.American Journal of Veterinary Research51: 17–21.Gasthuys, F. (1994) The value of 7.2% hypertonic salinesolution in anaesthesia and intensive care: mythor fact? Journal of Veterinary Anaesthesia21: 12–14.

ANAESTHETIC ACCIDENTS 533Hellyer, P.W., Meyer, R.E. and Olson, N.C. (1993)Resuscitation of anesthetized endotoxaemic pigs bythe use of hypertonic saline solution containingdextran. American Journal of Veterinary Research54: 280–286.Janssens, L., Altman, S. and Rogers, P.A.M. (1979)Respiratory and cardiac arrest under generalanaesthesia: treatment by acupuncture of nasalphiltrum. Veterinary Record 105: 273–276.Kein, N.D., Kramer, G.C. and White, D.A. (1991) Acutehypotension caused by rapid hypertonic salineinfusion in anesthetized dogs. Anesthesia and Analgesia73: 597–602.Kleeman, N.S. (1979) CNS manifestations of disorderedsalts and water balance. Hospital Practice 60–73.Maningas, P.A., DeGuzman, L.R., Tilman, M.S. et al.(1986) Small volume infusion of 7.5% NaCl in 6%Dextran 70 for the treatment of severe hemorrhagicshock in swine. Annals of Emergency Medicine1: 1131–1137.Mermel, G.W. and Boyle, W.A. (1986) Hypertonic salineresuscitation following prolonged hemorrhage in theawake dog. Anesthesiology 65(3A): 91.Moon, P.F., Snyder, J.R., Haskins, S.C., Perron, P.R. andKramer, G.C. (1991) Effects of a highly concentratedhypertonic saline-deltran volume expander oncaroiopulmonary function in anesthetizednormovolemic horses. American Journal of VeterinaryResearch 52: 1611–1618.Muir, W.W. and Sally, J. (1989) Small-volumeresuscitation with hypertonic saline solution inhypovolemic cats. American Journal of VeterinaryResearch 50: 1883–1889.NIOSH (1977) DHEW Publication No 77–140.Washington DC: US Government Printing Office.Podrid, P.J. (1991) Safety and toxicity of antiarrhythmicdrug therapy: benefit versus risk. Journal ofCardiovascular Pharmacology 17: (Suppl 6): S65–S73.Rocha, E., Silva, M., Irineu, I., and Porfirio, M. (1990)Hypertonic saline resuscitation: saturatedsalt-dextran solutions are equally effective, but inducehemolysis in dogs. Critical Care Medicine 18: 203–211.Waterman, A.E. (1981) Maintenance of bodytemperature during anaesthesia. Proceedings of theAssociation of Veterinary Anaesthetists of Great Britainand Ireland 9: 73–85.

Appendix IABBREVATIONSPACO 2PaCO 2PACO 2PaCO 2(A–a) PCO 2(A–a) PO 2ABPACADHAFBMRBPCa ++ or Ca 2+CNSCOCO 2COPDCPAPCPKCSFCVPCVSDCECGFRCgg/kgHbHCO − 3HRi.m.i.p.IPPVAlveolar CO 2 tensionArterial carbon dioxide tensionAlveolar O 2 tensionArterial oxygen tensionAlveolar to arterial CO 2 tension differenceAlveolar to arterial O 2 tension differenceArterial blood pressureAlternating currentAntidiuretic hormoneAtrial fibrillationBasal metabolic rateBlood pressureCalcium; calcium ionCentral nervous systemCardiac outputCarbon dioxideChronic obstructive airways diseaseContinuous airway pressureCreatine phosphokinaseCerebrospinal fluidCentral venous pressureCardiovascular systemDirect currentElectrogram; electrocardiographFunctional residual capacityGrammeGrammes per kilogramme body weightHaemoglobinBicarbonate; bicarbonate ionHeart rateIntramuscular; intramuscularlyIntraperitoneal; intraperitoneallyIntermittent positive pressure ventilation

536 APPENDIXi.t.Intratracheali.v.Intravenous; intravenouslyK +Potassium; potassium ionkPaKilopascal (1 kPa = approximately 7.5 mmHg)lLitresl/kgLitres per kilogramme body weightLVFLeft ventricular failureMABP Mean arterial blood pressuremgMilligrammesMg ++ or Mg 2+ Magnesium; magnesium ionmg/kg Milligrammes per kilogramme body weightmlMillilitresml/kg Millilitres per kilogramme body weightmmH 2 O Millimetres of watermmHg Millimetres of mercurymolMole = amount of substanceN 2NitrogenN 2 ONitrous oxideNa +Sodium; Sodium ionNONitric oxideO 2Oxygen°C Degrees CelsiusPAWP Pulmonary artery wedge pressurePCO 2 Carbon dioxide tensionPEEP Positive end-expiratory pressurePEFR Peak expiratory flow ratePiO 2Inspired O 2 tension or concentrationPO 2Oxygen tensionpsiPounds per square inchPVCPosterior vena cavaP – vCO 2 Venous CO –2 v= mixed venous tension)P – vO 2 Venous O –2 v = mixed venous tension)PVRPeripheral vascular resistanceSBPSystolic blood pressures.c.Subcutaneous; subcutaneouslys.w.g. Standard wire gaugeTLC(i) Total lung capacity or (ii) Tender loving careUKUnited KingdomVICVaporizer in the (breathing) circuitVOC Vaporizer outside the (breathing) circuitV/Q Ventilation: perfusion ratioVD (Anat) Respiratory anatomical deadspace volumeVD (Physiol) Respiratory physiological deadspace volumeVEsVentricular extrasystolesVFVentricular fibrillationV tTidal volume of respirationµg Microgrammesµg / kg Microgrammes per kilogramme bodyweightµl Microlitresµl / kg Microlitres per kilogramme bodyweight

Appendix IIOCCUPATIONAL EXPOSURE STANDARDSIn many countries there are maximum concentrations of inhalation anaesthetics in the atmosphere towhich workers may be exposed,either recommended or governed by regulations, and applying to allplaces of work. These concentrations vary from country to country and as yet there appear to be no specifiedlimits for sevoflurane or desflurane.1. The UKIn the UK, Occupational Exposure Standards (OES) were introduced in January 1996 for the four mainanaesthetic agents: N 2 O 100 ppm; halothane 10 ppm; isoflurane 50 ppm and enflurane 50 ppm. 1 Theseform part of the Control of Substances Hazardous to Health Regulations 1994 (COSHH) 2 with limits basedon an 8 hour time-weighted average (TWA). These limits were set as a consequence of alleged adverseeffects associated with human exposures.1 Health Services Advisory Committee (1995) Anaesthetic Agents. Controlling Exposure Under COSHH.London: HMSO.2 Control of Substances Hazardous to Health(COSHH) (1994) Regulations. Approved Code of Practice.London: HMSO.2. The USAMaximal levels of exposure have been suggested by the National Institute of Occupational Safety andHealth (NIOSH). 3 These are 2 ppm for halogenated anaesthetic agents and 25 ppm for N 2 O. 4,53 Whitcher, C. (1975) Development and evaluationof methods for the elimiantion of waste anaestheticgases and vapors in hospitals. NIOSH No. 75–137. Washington DC: Department HEW Publications.4 Rogers, D. (1996) Exposure to waste anesthetic gases. American Association of Occupational Health NursesJournal 34: 574–579.5 Yagiela, J.A. (1991) Health hazards and nitrous oxide: a time for reappraisal. Anesthetic Progress 38: 1–11.

Appendix IIIUK AND US NAMES OF SOME DRUGS USED IN ANAESTHESIAUS NameAcetominophenAlfadoloneAlfaxaloneBupivacaineBuprenorphineButorphanolCromylin sodiumDibucaineEpinephrineErgonovineFlunixineFurosemideGuaifenesinIsoprenterenolLidocaineMethohexitalMeperidinePentobarbitalPhenobarbitalQuinalbarbitoneSalbutamolScopolamineSuccinylcholineTetracaineThiopentalUK NameParacetamolAlfadoloneAlphaxaloneBupivacaineBuprenorphineButorphanolSodium cromoglycateCinchocaineAdrenalineErgometrineFlunixineFrusemideGuaiphenesinIsoprenalineLignocaineMethohexital (methohexitone)PethidinePentobarbital (pentobarbitone)Phenobarbital (phenobarbitone)SecobarbitalSalbutamolHyoscineSuxamethoniumAmethocaineThiopental (thiopentone)

IndexEntries in bold indicate main discussion, entries in italic denote illustrations and tables.Abbreviations, 535–6Abdominal muscles, neuromuscularblock, 154, 155Accidents, 507–32Acepromazine, 12, 76, 77–9α 2 adrenoceptor agonistcombinations, horse, 253cardiovascular side effects, 77contraindications, 78equine colic, 276etorphine combination, 99expiratory reserve volume (ERV)effect, 181ketamine combinationcat, 455obstetric anaesthesia, 484sheep and goat, 349opioid combinationscat, 442, 450dog, 398horse, 254papaveretum combination, 96postoperative analgesia,dog, 422premedication, 103, 124, 287caesarean section in bitch, 488cat, 450cattle, 331dog, 384–5, 398horse, 280sedationcardiac surgery, 498cat, 443cattle, 319dog, 385–6horse, 247–8, 252, 253pig, 370sheep and goat, 348see also Immobilon, Large AnimalAcetaminophen (paracetamol),contraindication in cat, 443Acetylcholinemuscarinic receptors, 6, 7neuromuscular transmission, 149,150–1, 153desensitisation, 152–3neuromuscular block, 155nicotinic receptors, 151,152, 152Acetylsalicylate see AspirinAcid-base status monitoring, 54–5Activated charcoal, 531Acupuncture, respiration stimulation,515–16Aδ fibres, 2Adrenaline, 83anaphylaxis/anaphylactoidreactions management, 529cardiac arrest management, 527local anaesthetic mixtures,230, 233Age characteristics, generalanaesthesia in dogs, 390, 394Air embolism, 202Air mattresses, 291, 291Airway management, 509–14aspiration of oesophageal/stomach contents seeAspiration of ingesta/stomach contentsbronchial spasm, 514laryngeal spasm, 511–12respiratory obstruction, 509tracheostomy, 513–14Airway resistance, 180, 180measurement, 180–1pregnancy-associatedchanges, 481Albumin, drug transportprocesses, 20, 21Alcuronium, 162, 173pharmacokinetics, 165Alfentanil, 95, 98cat, 442dog, 419etomidate combination, 98, 123premedication, 103sedative combinations, 101Allergic drug reactions, 25see also Anaphylactoid reactions;AnaphylaxisAllodynia, 4Alpaca see Llama and alpacaα 1 adrenoceptors, 83α 2 adrenoceptor agonist antagonists,517cattle, 318–19occupational exposure hazard, 531α 2 adrenoceptor agonists, 83–90benzodiazepinecombination, 295–6cat, 437–8cattle, 317–18clinical actions, 84–6, 91dog, 385, 387–8, 397epidural analgesia, 242, 252local anaestheticcombinations, 267horseacepromazinecombination, 253caesarean section, 486epidural block, 267intraoperative analgesia, 300maintenance of anaesthesia,293, 294, 295–6premedication, 280–1, 285, 286sedation of standing animal,248–52, 251, 253ketamine combination, 295–6horse, 485small mammals, 465obstetric anaesthesia, 484, 485occupational exposure hazard, 531opioid combinations, 101premedication, 104reversal of sedation, 90sheep and goat, 347sheep and goat, 347side effects, 85–6cardiovascular, 85, 248, 251α 2 adrenoceptor antagonists, 90–1α 2 adrenoceptors, 3, 83isoreceptors, 84results of stimulation, 84, 84structural aspects, 84Alphadolone, 119see also SaffanAlphaxalone, 119see also SaffanAlthesin, 119Alveolar uptake, inhaled anaesthetics,63, 63–4anaesthetic solubility, 64, 65, 65cardiac output effect, 69safety aspects, 66–7ventilatory depression, 69541

542 INDEXAmbu self-inflating bag, 515, 515Amethocaine, 227topical application, 233, 4404–Aminopyridine, 171xylazine antagonism incattle, 318Amphotericin, 22Anaemia, 51–2drug transport processes, 21Anaesthesia, mechanisms, 6–8Anaesthetic accidents, 29Anaesthetic gas analysers, 35, 35–6,57, 134errors with exhaledmethane, 36Anaesthetic risk, 15–16ASA classification, 16Analgesia, 91–101cat, 436, 442–3ancillary aids, 443premedication, 450–1dog, 385–91, 384thoracotomy, 430horse, 254–7colic, 276intraoperative, 300premedication, 281inhalation anaesthetics, 136rodents, 465small mammals, 465see also Postoperative analgesiaAnaphylactoid reactions, 529, 529Anaphylaxis, 31, 529, 529Angiotensin-converting enzyme(ACE) inhibitors, 393Anterior tibial artery, direct bloodpressure measurement, 44Antiarrhythmic drugs, 522Antibioticsdrug interactions, 275dog, 391, 391–2neuromuscular blockingagents, 417preoperative prophylaxis inhorse, 275Anticholinergic agents, 103–6α 2 adrenoceptor agonist combinations,252bradyarrhythmias management,522horse, 302clinical applications, 103obstetric anaesthesia, 482premedication, 103cat, 449, 450dog, 392–3horse, 280Anticholinesterases, 169–70, 174epidural injection, 243Antihistamines, 529Antipsychotic drugs see NeurolepticsAntlers harvesting, 361Anxiolytic drugs, 75premedication, 103Apex beat, 18Apnoea, 508–12anaesthetic drug overdose, 516artificial ventilation, 515carbon dioxide levels, 518causes, 516, 516immediate management, 514–15oxygen supply faults, 517–18postoperative neuromuscularblock complications, 174respiratory acidosis, 518Apnoea alarms, 49Apparatusbreathing systems, 208–18cleaning/sterilisation, 222endotracheal intubation, 219–21facemasks, 218–19inhalation agents administration,202–8intravenous agentsadministration, 197–202laryngoscopes, 221–2, 222Apparatus checks, 29, 508–9monitoring equipment, 57Apparatus resistance, 181–2Arterial blood pressure, 518blood loss response, 48, 518computer controlledanaesthesia, 13, 14, 14depth of anaesthesiaassessment, 12, 34general anaesthesia responsesin horse, 268–9measurement, 40direct methods, 43, 44, 44,45, 46Doppler ultrasound, 40–1,40, 41oscillometry, 42–4, 42monitoring, 36, 39–44cattle, 336dog, 414horse, 281sheep and goat, 356, 356Arterial pH monitoring, 49, 49–50Artificial ventilation, 179–95apnoea management, 515CPAP (continuous positive airwaypressure), 191–2high frequency lungventilation, 192–4intensive care, 194–5intrathoracic surgery, 493IPPV see Intermittent positivepressure ventilation (IPPV)neuromuscular block, 154PEEP (positive end-expiratorypressure), 191–2Ascending reticular activatingsystem, 7Aspiration of ingesta/stomachcontents, 30, 149, 172, 511–12cattle, 315, 315–16, 332dog, 396, 398llama/alpaca, 358sheep/goat, 341Aspirin (acetylsalicylate), 91–2cat, 443dog, 390Assisted ventilation, 182Asystole, 523Ataractics (tranquillizers), 75Atelectasis, general anaesthesia inhorse, 270, 270–1Atipamezole, 90, 91, 517detomidine reversal in horse, 250large Felidae anaesthesiareversal, 460medetomidine reversalcattle, 319llama and alpaca, 360obstetric anaesthesia reversal inpuppies, 489sedation reversalcat, 444sheep and goat, 348, 353wild animal anaesthesiatermination, 478xylazine antagonism in cattle, 319Atracurium, 163–4, 173dog, 416, 417, 417horse, 303–4obstetric anaesthesia, 485pharmacokinetics, 165Atrial fibrillation, 522Atrioventricular heart block, 38,39, 523Atropine, 104–5, 172, 174, 252bradyarrhythmiasmanagement, 522horse, 302ketamine combination, 128neuromuscular block reversal indog, 417–18premedicationcardiopulmonary bypass, 503cat, 454dog, 396horse, 280llama and alpaca, 358monkey, 477pig, 372rabbit, 466sheep and goat, 349Auditory evoked responses(AER), 10, 11Auricular arterydirect blood pressuremeasurement, 44, 44pulse, 37Auricular vein injectionpig, 372, 372–3, 373sheep and goat, 350Auriculopalpebral nerve blockcattle, 320, 320deer, 362dog, 430–7, 431horse, 259Autoclaving, 222Autonomic reflex-mediatedhypotension, 519

INDEX 543Awareness, 8Azaperone, 80etorphine combination,immobilisation ofelephant, 364pigcaesarean section, 487, 488premedication, 372sedation, 370–1Back support for horse, 291, 292Badger (Meles meles), 470‘Bagging’ (manual IPPV), 187Bain coaxial system, 211–12,212, 409feline anaesthesia, 457Ball float flowmeter, 204Barbiturates, 113, 114, 114–19caesarean section in bitch, 490chloral hydrate combination inhorse, 296drug interactions, 25dog, 391, 392obstetric anaesthesia, 485Base excess, 49, 54Bear, 475Behavioural monitoring parameters,31Benzocaine, 233general anaesthesia in fish, 466Benzodiazepines, 75–6, 80–3catpremedication, 451sedation, 444–5drug interactions in dog, 392fentanyl/fluanisone combinationin small mammals, 465flumazenil reversal, 83horseintraoperative musclerelaxation, 303maintenance of anaesthesia,294sedation, 252–3ketamine combinationhorse, 295–6small mammals, 465mode of action, 81opioid combinations, 101premedication, 104, 287, 451β blockers, 5225 β pregnanolone, 121Bicarbonate, 49, 54, 526Biochemical tests, preoperative, 19Bird, 472–5general anaesthesia, 473–4ketamine sedation, 129metabolic rate, 472respiratory tract, 472–3suxamethonium response, 166Bispectral Index (BIS), 11Blindness, intraoperativehypotension, 39Blood gases monitoring, 49, 49–50acid-base status monitoring, 54cattle, 336horse, 269, 281Blood glucose monitoring, 56–7Blood lossestimation, 48, 48, 518–19replacement, 48, 519Blood transfusion, 200Blood volume assessment, 48Blood warming coils, 200Bodcock seal, 202Body temperaturemonitoring, 55–6neuromuscular blockeffects, 168Bourdon pressure gauge, 202,203, 204Bovine anaesthesia see CattleBoyle vaporiser, 204, 206Brachial plexus block, 150dog, 428, 431, 431Brachycephalic dogs, 393, 412, 414respiratory obstruction, 514Bradycardia, 522followiing cardiac arrest, 527preoperative evaluation, 18Bradykinin, 2Brain-blood partition coefficient, 62Breath-holding response, 12Breathing depth monitoring, 48Breathing system (circuit), 68,208–18apparatus checks, 509cat, 456–7classification, 208cleaning/sterilisation, 222dog, 409facemask induction, 408–9low-flow administration, 410horse, 299–300non-rebreathing, 209–13occupational safety, 532open/semi-open methods,208–109pig, 379rebreathing, 213–18terminology, 218Bronchial carcinoma, 496Bronchial spasm, 512, 529Bronchiectasis, 497Bronchoscopy in dog, 424Bupivacaine, 91, 150, 228, 229absorption, 230cat, 443drug interactions, 392epidural analgesiadog, 431, 432, 433sheep and goat, 343, 343, 344infiltration analgesia, 234intra-articular injection indog, 428, 434intrapleural analgesia in dog, 434obstetric analgesia, 484specific nerve blocksdog, 428, 430, 431, 434, 435horse, 262Buprenorphine, 95, 99acepromazine combinationcat, 450dog, 398cat, 442, 460epidural nerve block, 242horse, 257postoperative analgesiacaesarian section, 487cat, 460rabbit, 467rat, 467sheep and goat, 357, 487premedication, 103, 349sequential analgesia, 100sheep and goat, 349, 361, 487Butorphanol, 94, 95, 100acepromazine combination incat, 460cattle, 320epidural analgesia, 96, 242caesarean section insheep/goat, 345dog, 432, 433lignocaine combination inhorse, 267horse, 267analgesia, 256–7colic, 276intraoperative, 300sedative combinations, 254postcaesarian section analgesiacat, 491goat, 487premedicationdog, 397, 398sheep and goat, 349, 352sequential analgesia, 100sheep and goat, 345, 348, 349, 352,357Butyrophenones, 75, 79–80opioid combinations(neuroleptanalgesia), 101,102, 102side effects, 79C fibres, 2Cachexia, suxamethonium durationprolongation, 166Caesarean sectionbitch, 487–9cat, 489–90cattle, 486horse, 486pig, 487–8postoperative analgesia, 486, 487,490, 491sheep and goat, 486, 487epidural analgesia, 343, 345Calcium channel blockers, 152, 516drug interactions in dog, 392Calcium infusion, 302Calcium ion channelsneuromuscular transmission, 152voltage gated, 6, 7

544 INDEXCalmodulin, 152Camel, 362, 362–3endotracheal intubation, 363local/regional analgesia, 363restraint, 362Capillary refill time monitoring, 39Capnography, 53, 53–4Captopril, 392Carbon dioxide absorptioncircle system, 215–16, 410soda lime, 213–14to-and-fro system, 214–15, 215Carbon dioxide gas cylinders, 205Carbon dioxide partial pressure(PCO 2 ), 49, 49, 50capnography, 53–4Carbon monoxide accumulation, 134Carbonic acid snow, 233Cardiac arrest, 31, 523–27, 529airway, 523breathing, 523circulation, 523–4direct cardiac compression, 526electrical defibrillation,525–26, 526external chest compression, 524–5,525hypovolaemia, 526intraoperative hypotension, 39,526parturition, 482resuscitation routine, 524, 524Cardiac arrhythmias, 12, 38–9,521–3cardiopulmonary bypass, 503hypercapnia, 50, 522Cardiac auscultation, 18Cardiac catheterisation, 499Cardiac murmur, 18Cardiac outputblood loss response, 48inhaled anaesthetic uptake, 69measurement (monitoring), 47–8oxygen availability relationship,19–20pregnancy-associated changes,481, 482Cardiac surgery, 498–515cardiac catheterisation, 499cardiopulmonary bypass, 502–4hypothermia, 499–502pacemaker insertion, 505, 505ultrasonography, 499Cardiac tamponade, 498, 499Cardiac thrill, 18Cardiogenic shock, 520Cardiopulmonary bypass, 502–4general anaesthesia, 503postoperative care, 504–5premedication, 503rewarming, 504Cardiovascular diseasedog, 420, 423–4preoperative evaluation, 17–18,19–20Cardiovascular functioncat, 457cattle, 338horse, 268–9pregnancy-associated changes,481–2, 483Cardiovascular function monitoring,36, 36–48arterial blood pressure, 39–45blood loss, 48cardiac output, 47–8central venous pressure, 45–6depth of anaesthesiamonitoring, 34heart rate, 36–9left atrial pressure (pulmonaryartery wedge pressure), 46–7tissue perfusion, 39Carfentanil, 98–9sedationdeer, 362sheep and goat, 349wild animal immobilisation, 478Carprofen, 92–3cat, 444dog, 390horse, 255Castrationcattle, 326horsegeneral anaesthesia, 283,288, 294local analgesia, 264, 264–5llama and alpaca, 358pig, 378, 382–3sheep and goat, 342Cat, 441–60analgesia, 442, 442–3, 450–1ancillary aids, 443breathing systems, 456–7caesarean section, 490–1cardiovascular data, 457chest closure, 495defibrillation, 525endotracheal intubation, 446–9epidural analgesia, 443, 460, 490facemask anaesthesia, 446,447, 456general anaesthesia, 445–59inhalation agents, 441, 457–8intravenous agents, 441, 450,451–6kittens, 459problems, 441, 459hypothermia, 528induction chamber, 456, 456intermittent positive pressureventilation (IPPV), 459intravenous technique, 445–46,445, 446laryngeal spasm, 505local analgesia, 443, 460neuroleptanalgesia, 442neuromuscular blocking agents,167, 459obstetric anaesthesia, 490–1opioid analgesic antagonists, 516pain behaviour, 442perianaesthetic mortality,441, 445, 450peripheral nerve stimulationsites, 159postoperative care, 459–60preanaesthetic preparation, 445premedication, 441, 442, 443,449–51regurgitation, 513restraint, 441, 442, 445, 446,456, 460sedation, 443–5, 450, 495tracheostomy, 513, 514Catenary three compartment model,72, 73Catheter insertioncattle, 331dog, 401epidural analgesia, 433, 433horse, 277jugular vein, 278–80, 279pig ear-flap (auricular) vein,372, 373technique, 198–9, 199‘Catheter over needle’, 198, 198Catheters, 197–200, 198flow rates, 199–200length, 280small vein sets, 200, 200Cattle, 315–38aspiration of ingesta, 315, 513prevention, 315–16, 315defibrillation, 526endotracheal intubation, 316,333, 332–3general anaesthesia, 331–8drug combinations, 332inhalation agents, 336–7intravenous agents, 333–56monitoring, 337–8positioning, 338premedication, 332recovery, 338intravenous injection, 332intravenous regional analgesia,331, 331local analgesia, 320–31castration, 326caudal epidural, 326–8, 326lumbosacral epidural, 328–9,329, 486neuromuscular blocking agents,167, 337–8obstetric anaesthesia, 486peripheral nerve stimulationsites, 160pleural cavity drainage, 495preoperative preparation,316–17, 331–2recumbency-associated problemsbloat, 315pulmonary ventilation, 316

INDEX 545restraint, 317salivation, 316sedation, 317–20specific nerve blocks, 320–31auriculopalpebral, 320, 320cornual, 320–1, 321digital nerves, 329–31, 329, 330inverted L block, 322paravertebral, 322–5, 323peribulbar, 321–2Petersen eye block, 321,321, 322pudic (internal pudendal),325–6, 323, 324retrobulbar, 321–2Caudal block, 240–1cattle, 326, 326–8, 486horse, 252, 265–6, 266indications, 266, 485–86opioids, 257llama and alpaca, 358obstetric anaesthesiacattle, 486horse, 485–86sheep and goat, 486sheep and goat, 342–3, 343, 486Central nervous systemlocal anaesthetic toxicity, 231–2monitoring, 31, 33, 33–4Central venous pressure monitoring,45–6, 47Centrally acting muscle relaxants,174–5, 191dog, 416horse, 302–3Cephalic vein injectioncat, 445, 445, 446dog, 398, 399, 399short-legged breeds, 400sheep and goat, 349, 350Cerebral function monitoring,electroencephalography(EEG), 10Checking apparatus, 29, 508–9monitoring equipment, 57Chelonia, 470Chest deflation reflex, 515Cheyne-Stokes respiration, 516Chinchocaine, 227Chloral hydrate, 75, 104, 125, 127cattle, 319–20horse, 253barbiturates combination, 296Chloralose, 125–6Chloramphenicol, 391Chlordiazepoxide, 80Chloroform, 138, 208horse, 288Chloroprocaine, 228dental nerves infiltration indog, 433metabolism, 231Chlorpromazine, 12, 76, 79dog, 385Choline acetyl-O-transferase, 151Cholinesterase, 166, 166species differences, 167Circle carbon dioxide removal system,214–15, 215, 410Circulatory failure, 518–27autonomic reflex activity, 519cardiac rhythm disturbances,521–23fluid volume inadequacy, 518–20shock, 520–21Cisatracurium, 416Classical signs of anaesthesia, 11–13Cleaning apparatus, 222Clenbuterol, 272, 273Climazolam, 83cat, 445horse, 252Clonidine, 83, 84epidural nerve block, 242Coaxial breathing systems,211–12, 212feline anaesthesia, 457Cocaine, 227, 232spinal nerve block, 236Cole pattern endotracheal tube,290, 290Colic, equine, 250, 255, 513, 521analgesia, 276general anaesthesia, 276–7Compartment syndrome inhorse, 273Compliance, 182–3, 182Compound A, 414Computer controlled anaesthesia,13–15, 36continuous infusion, 113fuzzy logic control, 14–15, 14intravenous infusion regimens,73, 74Concentration effect, 69Connell flowmeter, 204Constant infusion (volumetric)pumps, 200, 201Context sensitive half-time(t 1context ), 702Continuous intravenous infusion,73, 405, 405Continuous positive airway pressure(CPAP), 191–2Control of Substances Hazardous toHuman Health (COSHH)regulations, 144, 145Cooke intraosseous needle, 402Corneal analgesia, 233Corneal reflex, 33Cornual blockcattle, 320–1, 321sheep and goat, 341–42, 342Corticosteroidsanaphylaxis/anaphylactoidreactions, 529cat preanaesthetic preparation, 445drug interactions in dog, 392, 391endotoxic shock, 521epidural injection, 243Cough, preoperative evaluation, 17Coughing response, 12Cox’s mask, 288C SS95 , 164, 165, 165Cyanosis, 31, 508Cyclopropane, 138physical characteristics, 133Cytokines, 2Dalton’s law, 61Dantrolene sodium, 370Deer, 361–2anaesthetic agents, 361–2handling recommendations, 361harvesting antlers, 362local analgesia, 362Defibrillation, 525–6, 526, 528Definitions of anaesthesia, 1Dehorningcattle, 321sheep and goat, 341–2Dehydration, intraoperative,21, 22, 23Dental nerves infiltration in dog, 434Depth of anaesthesia, 8–11, 12, 31,33, 33anaesthetic gas analysers, 35, 35–6blood pressure, 34classical signs, 11–13heart rate, 34respiratory rate, 34Desflurane, 142, 142–3general anaesthesiacat, 458cattle, 337horse, 298–9pig, 379, 380inhalation induction in foal, 288obstetric anaesthesia, 484caesarean section in bitch, 489pharmacokinetics, 66induction speed, 66partition coefficient, 62, 65physical characteristics, 133Detomidine, 35, 84, 87blood pressure response, 39cattle, 318obstetric anaesthesia, 486caudal injection, 252epidural nerve block, 242opioid combination, 257xylazine/mepivacainecombination, 485horse, 249–50, 251, 252, 294acepromazine combination,253atipamezole reversal, 250butorphanol combination, 254colic, 276obstetric anaesthesia, 485premedication, 280–1, 285, 286ketamine combination, 128deer, 362sheep and goat, 348‘triple drip’ anaesthesia, 175

546 INDEXDexamethasone, 25Dexmedetomidene, sedation incat, 444Diabetes insipidus, 18Diabetes mellitusdog, 392, 393intraoperative hypoglycaemia, 57preoperative evaluation, 18, 19preoperative preparation, 24Diaphragm, neuromuscular blockclinical evaluation of paralysis, 159sensitivity, 154, 155Diaphragm rupture repair, 497–8Diastolic arterial pressure (DAP), 39Diazepam, 82cat, 444, 451dogfentanyl combination, 407, 425morphine combination, 495oxymorphone combination,407, 425horse, 252ketamine combination, 128caesarean section in cat, 490caesarean section in sow, 487cardiac catheterisation, 499cat, 455, 490dog, 425sheep and goat, 342, 349,352–3ketamine/medetomidinecombination in rabbit, 466premedicationcalves, 332cardiopulmonary bypass, 503cat, 451sheep and goat, 348caesarean section underepidural block, 345, 486Diethyl ether, 8, 137–8breathing systems, 208cat, 457–8fish, 471pharmacokinetics, 66physical characteristics, 133Diffusion hypoxia, 66, 137Digital nerve blockcattle, 329–31, 329, 330dog, 434, 433sheep and goat, 343Digoxin, 522Diltiazem, 392Dimethyl ether of d-tubocurarine, 161DINAMAP, 42, 42–4Diprenorphine, 99, 101, 102etorphine antagonism, 99,102, 516elephant, 364, 365wild animal anaesthesiatermination, 478Dipyrone, 254Dissociative agents, 127–9horse, 286pig, 371Dissociative anaesthesia, 127Distribution half-life (t 1α),2non-depolarisingneuromuscular blockingagents, 164, 165Dobutamine, 39, 273, 357, 364, 388,419, 527cardiovascular depression inhorse, 301Dog, 385–435aspiration of vomited material, 513brachycephalic breeds, 393,412, 414respiratory obstruction, 510caesarean section, 487–9cardiac disease, 421, 423–4defibrillation, 525diabetes management, 392, 393drug interactions, 392, 391–2endoscopy, 424endotracheal intubation, 410–12,411, 413, 428–9, 428epidural analgesia, 428, 430, 431–4,432, 433obstetric anaesthesia, 488, 489gastric dilatation/volvulussyndrome, 424–5general anaesthesiaanalgesia supplements, 418–19breed-specific problems,392–3cardiovascular complications,419–20, 420facemask induction, 404–5fluid therapy, 418, 419, 429geriatric animals, 394, 394impact of disease, 396inhalation agents, 408, 408–16intravenous agents, 402–8monitoring, 416, 418overweight (obese) animals,394paediatric animals, 394, 394positioning, 418ventilation, 414, 415–16heart rate palpation, 36, 37hepatic disease, 425, 426hypothermia, 528intermittent positive pressureventilation (IPPV), 415–16, 419,426, 428intra-articular analgesia, 434intrapleural analgesia, 434intrathoracic surgerypleural cavity drainage, 495thoracotomy, 429–30, 429intravenous regional analgesia,434–5intravenous technique, 398–402,395, 399catheter insertion, 401intraosseous injection, 401–2vascular port, 402local analgesia, 430–36neuroleptanalgesia, 397, 398,407–8, 425neurologic disease, 425–7, 427intracranial pressureelevation, 426myelography, 426–7neuromuscular blocking agents,167, 168, 416–18, 417termination, 417–18obstetric anaesthesia, 487–9opioid analgesic antagonists, 516orthopaedic surgery, 427–8, 428peripheral nerve stimulationsites, 159postoperative management,420–3analgesia, 422–3, 422oxygen supplementation, 421,422premedication, 386–7, 390,396–8, 397preoperative preparation,391–6auscultation of thorax, 395–6food/water restriction, 396renal disease, 429, 429restraint, 398, 399, 399sedation, 385–9, 386, 494Boxer breed, 385specific nerve blocks, 430–1auriculopalpebral, 430–1, 430brachial plexus, 430, 431dental nerves, 433digital, 433, 434intercostal, 433–4tracheostomy, 513Dopamine, 6, 39, 357, 419, 527cardiovascular depression inhorse, 301renoprotection, 22Dopexamine, 302Doppler ultrasound blood pressuremeasurement, 40, 40–1, 41Dorsal horn laminae, 2, 3Dorsal pedal artery, direct bloodpressure measurement,43, 44Double burst stimulation (DBS),158, 158Doxacurium, 416pharmacokinetics, 165Doxapram, 272, 464, 517newborn foal resuscitation, 485sedation reversal in sheep andgoat, 348Drip rate controller, 200Droperidol, 80fentanyl combination, 102pig, 371Drug adverse effects, 24–5Drug interactions, 25dog, 392, 391–2Drug metabolism, 20, 20Drug names, UK/USA, 539Drug overdosage, 24–5hypoxaemia, 516–17inhalation agents, 66, 67

INDEX 547Drug transport processes, 20–1Dulaa, 361Dynorphin, 93Edrophonium, 169, 170, 171, 418Electrocardiogram (ECG)anaesthesia monitoring inhorse, 281heart rate monitoring, 38, 38–9hypothermia response, 500Electroencephalography (EEG), 4cerebral function monitoring, 10computer controlledanaesthesia, 36depth of anaesthesia, 8–11evoked responses, 10–11, 11power spectrum analysis, 9–10,9, 10sleep-associated thalamocorticalactivity, 8Electroimmobilisation of cattle, 317Electromechanical dissociation, 523Electromyogram (EMG),neuromuscular blockmonitoring, 158–9, 160Elephant, 363–5body weight estimation, 363endotracheal intubation, 364immobilisation, 363–4inhalation anaesthesia, 364–5premedication, 364Elimination half-life (t 1β )2intravenous anaesthetics, 70, 73non-depolarising neuromuscularblocking agents, 164, 165Emergencies, 507–32Emergency proceduresdiabetes mellitus management, 24equine colic, 276–7preanaesthetic preparation, 22horse, 275–6EMLA cream, 197, 233, 446EMO (Epstein-Mackintosh-Oxford)vaporiser, 207, 208Emu, 475Enalapril, 392Encephalins, 93, 136End tidal carbon dioxide (E T CO 2 ),53–4End-plate potential, 150Endorphins, 93, 136Endoscopy in dog, 424Endotoxaemia, 57Endotoxic shock, 520, 521Endotracheal intubation, 171, 172,219, 532bird, 474, 474camel, 363cardiac catheterisation, 499cardiac surgery, 498cat, 446–9, 448laryngospasm prevention,446–7technique, 447–8, 450tube size/length, 448, 449cattle, 316, 333, 332–3dog, 410–12, 411, 413brachycephalic breeds, 412mandibular fracture repair,428–30, 428elephant, 364high frequency lungventilation, 193horse, 289, 289–90, 290intermittent positive pressureventilation (IPPV), 194llama and alpaca, 359, 359–60monkey, 476pig, 373, 373–4rabbit, 466sheep and goat, 350–1, 351snake, 470, 471tube occlusioncuff overinflation, 510, 511kinked tube, 510, 510Endotracheal tube removalcat, 459cattle, 338horse, 306Endotracheal tubes, 219–21, 220length, 221reinforced, 221Enflurane, 141–2caesarean sectionbitch, 488sow, 487cardiovascular responses,12, 135cat, 452horse, 298neuromuscular blocking agentpotentiation, 135, 168obstetric anaesthesia, 484partition coefficient, 62, 65physical characteristics, 133pig, 377recovery time, 141respiratory responses, 69, 181toxicity/hepatitis, 135, 142Enzyme function, 20, 20Ephedrine, 39Epidural analgesia, 150, 236, 241bradyarrhythmias management,522caesarean sectionbitch, 488cat, 490postoperative analgesia, 487sheep and goat, 486cat, 443, 460, 490cattle, 326–9, 326, 329caudal block see Caudal blockcontinuous, 243dog, 428, 430, 431–4, 432,432, 488complications, 434drugs, 432drugs, 241–3horse, 252, 257, 265–7, 266obstetric anaesthesia, 485–6opioid/α 2 adrenoceptoragonist-local anaestheticcombinations, 267obstetric anaesthesia, 484cattle, 486sheep and goat, 486opioids see Opioid analgesicspig, 381, 381–3problems, 243–4, 531bloody tap, 244total spinal block, 244sheep and goat, 343, 344, 344–6, 486solution preservativeneurotoxicity, 243spread of analgesia, 238–9see also Spinal nerve blocksEpidural space, 236–8Equipment maintenance, 29Ergometrine, 483bitch, 488horse, 486sow, 488Ether see Diethyl etherEthyl chloride spray, 233Ethylene oxide sterilisation, 222Etidocaine, 228Etodolac, 390Etomidate, 122–3alfentanil combination, 98, 123dog, 407horse, 286Etorphine, 99acepromazine combination, 99azaperone combination, 364diprenorphine reversal, 99, 102, 516elephant, 364, 365elephant immobilisation, 364horse, 287–8methotrimeprazine combination,99occupational exposure hazard, 531sheep and goat, 349wild animal immobilisation, 471see also ImmobilonEugenols, 123Evoked responses,electroencephalography (EEG),10–11, 11Expiration, 179, 179Expiratory reserve volume (ERV), 181Expired air ventilation, 515Explosions, anaesthetic, 530External chest compression, 524–5,525Eye position, depth of anaesthesia,12–13, 33, 33–4, 34Eye reflexes, depth of anaesthesia,33, 33Face mask induction/ventilationbird, 474cat, 450, 447, 456IPPV application, 459manual ventilation oflungs, 448

548 INDEXFace mask induction/ventilation(contd.)dog, 408–9monkey, 476pig, 375, 379rabbit, 466rat, 466small mammals, 454Face masks, 218–19, 219Facial arterydirect blood pressuremeasurement, 37, 44, 45pulse, 37, 37Facial muscle block, 154Facial nerve damage, 274, 274, 529Fasting, preanaesthetic, 17, 22–3bird, 472camel, 363cat, 445cattle, 316–17, 332dog, 396horse, 275llama and alpaca, 358pig, 371sheep and goat, 349Felidae, large, 460Femoral arterydirect blood pressuremeasurement, 44pulse, 37Femoral nerve damage,horse, 274–5Femoral vein injection, dog, 398,401Fentanyl, 95, 97cat, 442cutaneous patch (transdermalsystem), 97, 97postoperative analgesia in dog,422–3dog, 419, 422, 432, 433diazepam combination,407, 425epidural analgesia, 96, 242dog, 432, 433fluanisone combinationhedgehog, 470small mammals, 465ketamine combination inrabbit, 466premedication, 103sedative combinations, 101neuroleptanalgesia, 102,102total intravenous anaesthesia(TIVA), 114Ferret (Mustela putorius furo), 469Fibular nerve block see Peronealnerve blockFires, 529First order processes, 71, 71, 72First pass effect, 70Fish, 471–2Flowmeters, 203, 203–5apparatus checks, 508Fluanisone, 80fentanyl combination, 102hedgehog, 470small mammals, 465Fluid and electrolytes, preoperativepreparation, 23Fluid therapyblood loss replacement, 519cardiac arrest, 526–7general anaesthesiadog, 418, 419, 429horse, 301monkey, 476–7sheep and goat, 356preoperative preparation, 23shock, 520, 521Flumazenil, 83sheep and goat, 348Flunixin, 92endotoxic shock, 521horse, 255colic, 276Fluorination, 134‘Flutter valve’ apparatus, 202Foetal drug exposure, 483Foetal haemoglobin, 484Forelimb desensitisationcattle, 329, 329horse, 262, 262–3median nerve block, 262musculocutanoues nerveblock, 262–3ulnar nerve block, 262Forelimb surgery, dog, 428Fractures, local anaesthesia, 236Free fall control, horse, 281–2, 282Functional magnetic resonanceimaging (fMRI), 4Functional residual capacity,pregnancy-associated changes,482, 483Fuzzy logic, 14–15, 14GABA (γ amino butyric acid)neurotransmission, 81Gallamine, 161–2, 173pharmacokinetics, 165train-of-four (TOF) stimulationresponse, 157γ motor fibres, 149Gas concentrations in solution, 62Gas delivery apparatus, 202–6apparatus checks, 508flowmeters, 203–5, 203gases other than oxygen, 205–6oxygen cylinders, 202oxygen failure warningdevices, 205pipeline systems, 205pressure gauges, 202, 203reducing valves/regulators,203, 205Gastric contents aspiration seeAspiration of ingesta/stomachcontentsGastric dilatation/volvulussyndrome, dog, 424–5Gastro-oesophageal reflux, dog, 420–1Gastrointestinal endoscopy,dog, 424Gate control method, horse, 282, 282General anaesthesia, 1, 2depth, 8–11classical signs, 11–13selection issues, 16–17General anaesthetic agentsactions, 6–8toxicity, 16Gentamycin, 22, 275Gerbil, 469, 469Glycine neurotransmission, 81Glycopyrrolate, 105, 172, 252bradyarrhythmias management,522horse, 302neuromuscular block reversal indog, 417–18obstetric anaesthesia, 484premedicationdog, 396horse, 280pig, 372sheep and goat, 349rabbit, 466Goat see Sheep and goatGoldman vaporiser, 207, 207, 217Guaiphenesin, 149–50, 174–5accidental perivascular injection,529contraindication for obstetricanaesthesia, 485general anaesthesiacamel, 363horse, 294, 302–3llama and alpaca, 360sheep and goat, 354–5ketamine combination incattle, 335ketamine/xylazine combination(triple drip), 175, 295pig, 378–9thiopental combinationcattle, 332, 333horse, 285Guinea pig, 464, 468physiological measurements,464Gum colour monitoring, 39Haemoglobindesaturation, 507–9detection, 507–8preventive checklist, 508–9foetal, 484oxygen availability relationship,19, 20oxygen saturation, 51, 51pregnancy-associatedchanges, 481preoperative evaluation, 24

INDEX 549Haemorrhage, surgical, 518–19Hall mask, 447, 448Halogenation, 134Halothane, 138–9aterial blood pressure reponse, 12caesarean sectionbitch, 488cattle, 486horse, 486sow, 482cardiovascular effects, 12, 50,412–14horse, 268chemical stability, 134drug interactions in dog, 392expiratory reserve volume (ERV)effect, 181eye movements, 33general anaesthesiabear, 475bird, 474, 475camel, 363cardiopulmonary bypass, 503cat, 458cattle, 336chelonia, 470deer, 363dog, 409, 412–13elephant, 364ferret, 469gerbil, 469guinea pig, 468hamster, 469horse, 297, 298, 300llama and alpaca, 360mink, 469monkey, 476pig, 381–2rabbit, 467rat, 467rodents, 464sheep and goat, 355skunk, 469small mammals, 463snake, 469hepatic damage, 135, 139inhalation induction in foals, 288minimum alveolar concentration(MAC), 35monitoring, 36neuromuscular blocking drugpotentiation, 135, 168non-inflammability, 134occupational safety, 139exposure standards, 144, 144partition coefficient, 62, 65physical characteristics, 133pontine reticular formationactions, 8recovery time, 141horse, 297respiratory despression, 69total respiratory resistance effect,181toxic metabolites, 135Hamster, 469, 469physiological measurements, 464Handling accidents, 529Hare (Lepus europaeus), 465–7, 466Heart block, 38, 39, 523Heart ratedepth of anaesthesia assessment,12, 34hypothermia response, 502monitoring, 36–9electrocardiography, 38–9, 38oesophageal stethoscope,36, 37–8palpation, 36, 37, 37Heart rate monitors, 36–9Heat stroke see HyperthermiaHedgehog (Erinaceus europaeus), 470Heidbrink flowmeter, 204Heimlich valve, 496, 496Y-connector, 495, 499, 496Helium, 134Hellabrunn mixture, 465Hen, domestic, 464Henry’s law, 61Hepatotoxicityinhalation anaesthetics, 135, 139NSAIDs in cat, 443thiopenta, 117High frequency jet ventilators, 194High frequency lung ventilation,192–4carbon dioxide elimination, 194methods, 193–4oxygen delivery, 194pressure-flow relationships, 193High frequency oscillators, 194Hind limb desensitisation, distalcattle, 330, 330horse, 263, 263peroneal (fibular) nerveblock, 263saphenous nerve block, 263tibial nerve block, 263sheep and goat, 347, 347Hind limb surgery, dog, 428Horse, 247–307analgesia, 254–7intra-articular injections, 257NSAIDs (non-steroidalanti-inflammatory drugs),254–5opioid analgesics, 255–7, 256caudal block, 257, 265–6defibrillation, 525endotracheal intubation, 289,289–90, 290epidural analgesia, 265–7, 266obstetric, 485–6general anaesthesia, 267–307atelectasis, 270–1, 270breathing systems, 299–300cardiovascular effects, 268–9circulatory depressiontreatment, 300–2emergencies, 275–6facilities, 281hypoxaemia, 269, 272–3induction, 281–9inhalation agents, 288–9,297–300inotropic agents, 301–2intercompartmental pressurein limbs, 273intermittent positive pressureventilation (IPPV), 305–6intravenous agents, 283–8, 284,292–7, 295intravenous fluid infusion, 301lung volume reduction, 271–2maintenance, 289–300, 295monitoring, 281movement while unconscious,267muscle blood flowimprovement, 273, 274neuropathy, 273, 274–5, 274,529pharmacological oxygenationimprovement, 272–3positioning, 290–2, 291, 292postanaesthetic myopathy(rhabdomyolysis), 272,273–4premedication, 280–1preparation, 275–6pulmonary changes, 269–73recovery, 267–8, 269,297, 306–7right-to-left intrapulmonaryshunt, 271size-related problems, 267–8temperament of animal, 267–8venous admixture, 271weight support duringinduction, 281–2, 282, 283heart rate palpation, 37, 37intravenous techniques, 277–80,278local analgesia, 257–67castration, 264, 264–5neuromuscular blocking agents,167, 302–5obstetric anaesthesia, 484–6opioid analgesic antagonists, 517paravertebral block, 265, 265peripheral nerve stimulation sites,159–60, 160physiological dead space:tidalvolume ratio, 271pleural cavity drainage, 495, 496postoperative analgesia, 306recumbency onset, 283, 286free fall control, 281–2, 282gate control method, 282, 282tilting table control method,282, 283recumbency-associated problems,268, 270, 271, 273obstetrics, 485respiratory obstruction, 510

550 INDEXHorse (contd.)sedation of standing animal,247–54acepromazine, 253α 2 adrenoceptor agonists,248–52benzodiazepines, 252–3chloral hydrate, 253drug combinations, 253–4opioid combinations, 253–4,254phenothiazines, 247–8reserpine, 253for transportation, 250soft palate blockage of airway, 511specific nerve blocks, 257–65auriculopalpebral, 259complications, 263–4distal hindlimb desensitisation,263forelimb desensitisation,262–3, 262infraorbital, 257–8, 258, 259mandibular, 258–9, 258mental, 258, 259needle accidents, 263palmar/plantar, 260–2supraorbital, 258, 259spinal nerve anatomy, 265subarachnoid anaesthesia, 267total intravenous anaesthesia(TIVA)induction regimes, 283–8, 284long procedures, 296–7maintenance of anaesthesia,292–7medium duration procedures,294–6, 295short procedures, 293–4tracheostomy, 513weight estimation, 277, 277Humanitarian considerations, 1Humidification of inspired gases,194–5Humphrey ADE system, 212–13Hydromorphone/acepromazinecombination in dog, 3985–Hydroxytryptamine, 6Hyoscine, 105–6papaveretum combination(‘Omnopon’), 96, 106dog, 397premedication, 503Hyperalgesia, 2, 3, 4Hypercapnia, 50acid-base status, 54cardiac arrhythmias, 50, 522neuromuscular blockpotentiation, 168Hyperthermia, 55–6, 528–9Hypertonic saline, 521‘Hypnorm’, 102Hypnotics, 104definition, 75Hypoalbuminaemia, 21Hypoglycaemia, 56–7Hypoproteinaemia, 21Hypotensionautonomic reflex activity, 519cattle, 337consequences, 39–40definition, 39hypovolaemia, 518–19inhalational agents in horse,268–9, 300postanaesthetic myopathy(rhabdomyolysis), 273treatment, 39, 518, 522dog, 386, 419elephant, 364fluid therapy, 517sheep and goat, 357Hypothermia, 55, 55, 528blood viscosity changes, 200cardiac surgery, 499–502temperature monitoring, 500cat, 450, 459neuromuscular block effects, 168,174peripheral nerve stimulationeffect, 160physiological responses, 500–1sheep and goat, 357small mammals, 463, 528techniques for production, 501–2trauma surgery in dog, 428Hypovolaemia, 518–20cardiac arrest, 526central venous pressuremonitoring, 45–6preoperative volumerestoration, 23Hypovolaemic shock, 520Hypoxaemia, 50, 52anaesthetic drug overdose, 516–17cattle, 316–17horse, 269, 272–3recovery period monitoring, 31Ibuprofen, contraindication in cat, 443Idazoxan, 84, 90xylazine antagonism in cattle, 318Idiosyncratic drug reactions, 25Immobilon, 102–3, 478Large Animal, 78, 99deer, 362horse, 287–8occupational exposuremanagement, 288Small Animal, 99, 387Induction chambercat, 456, 456ferret, 469gerbil, 469hamster, 469hedgehog, 470mink, 469rabbit, 467rat, 467skunk, 469small mammals, 464snake, 471stoat, 469weasel, 469Induction monitoring, 30, 31Inferior alveolar nerve block,dog, 433Infiltration analgesia, 234–5Inflammatory process, painmechanisms, 2–3Infraorbital nerve blockdog, 433horse, 257–8, 258, 259Infusion apparatus, 200–2, 201Inhalation agentsadministration, 67–9, 68analgesia, 136apparatus, 202–8anaesthetic gases delivery,202–6dog, 409safety checks, 508–9vaporisers, 206–8biotransformation, 134–5cardiovascular funciondepression, 135horse, 268, 300–2chemical stability, 134depth of anaesthesiaassessment, 12drug interactions, 135–6general anaesthesiabird, 474cat, 441, 457–8cattle, 336dog, 408, 408–16elephant, 364–5horse, 288–9, 297–300llama and alpaca, 360–1monkey, 476pig, 379–80rabbit, 467rat, 467rodents, 464sheep and goat, 355small mammals, 464induction chamber use seeInduction chambermyocardial sensitization tocatecholamines, 135neuromuscular blocking drugpotentiation, 135–6non-inflammability, 133–4obstetric anaesthesia, 484occupational exposure, 144,144–5, 531pharmacokinetics, 63–9blood solubility, 64–5, 64, 66brain tissue tension, 65–6clinical aspects, 67induction speed, 66lung wash-in, 64lung wash-out, 66overdosage, 66, 67potency, 67

INDEX 551recovery from anaesthesia,66, 67uptake, 63–4, 63, 67, 69volatility, 67pharmacology, 133–45physical characteristics, 133respiratory depressant effects,69, 135toxic effects, 134volatility, 67Injectable agents, 113–29bird, 473–4rat, 467, 467Inotropic supportfollowiing cardiac arrest, 527horse, 301–2Inspiration, 179, 179Insulin therapydiabetic dog, 392, 392preoperative preparation, 24Insulinoma, 57Intensive care, lung ventilation, 194–5Intercompartmental pressure inlimbs, horse, 273Intercostal nerve block in dog, 430,433–4Intermittent bolus doses, 72, 72, 73Intermittent positive pressureventilation (IPPV), 179adverse effects, 186after opening pleural cavity, 184–7cardiovascular responses, 186collapse of lung, 184–5, 185mediastinal movement, 185–6paradoxical respiration,185, 185cardiac arrest, 524, 526, 527cardiac catheterisation, 499cardiopulmonary bypass, 503cat, 459cattle, 337circulatory system effects, 183, 184continuous positive airwaypressure (CPAP), 191–2dog, 415–16, 419intracranial pressureelevation, 426thoracotomy, 429expiratory phase subatmosphericpressure application, 184expiratory resistance, 184face mask/inadvertent stomachinflation, 187gas flow rate, 184horse, 271, 305–6caesarean section, 486humidification of inspired gases,194–5intensive care, 194–5mean intrathoracic pressure, 183pig, 374, 375positive end-expiratory pressure(PEEP), 191–2positive pressure application,183–4practical management, 187–95lung ventilators, 187–91,188, 189, 190manual ventilation, 187spontaneous breathingmovements abolition, 187pulmonary surgery, 497thoracic surgery, 182–7, 493weaning, 191Internal pudendal nerve block seePudic nerve blockIntracranial pressure elevation,dog, 426Intraosseous injection, dog, 401–2Intraperitoneal injection, pig, 373–4Intrapleural analgesia, dog, 434Intrasynovial analgesia, 234dog, 428, 434horse, 257opioids, 257, 428Intrathoracic surgery, 493–505cardiac surgery, 498–505closure of chest, 493–6diaphragm rupturerepair, 496–7oesophageal surgery, 496thoracotomy, 496pulmonary surgery, 497–8Intravenous agents, 113–29, 114administration apparatus,197–202barbiturates, 114, 114–19computer-controlled continuousinfusion, 113dissociative agents, 127–9drug delivery methods, 73–4general anaesthesiacat, 441, 450, 451–6cattle, 333–6dog, 402–8horse, 283–8, 284, 292–7, 295llama and alpaca, 360monkey, 475pig, 376–9rabbit, 466sheep and goat, 351–5, 353small mammals, 464–5less rapidly acting drugs, 125–7level of anaesthesia, 113obstetric anaesthesia, 484pharmacokinetics, 69, 69–74elimination half-life(t1β), 702multicompartment model, 73one compartment model, 71–2,71, 72total apparent volume ofdistribution, 69–70total elimination clearance(Cl E ), 70two compartment model,72–3, 72rapidly-acting drugs, 119–25speed of reversal, 113see also Injectable agentsIntravenous regional analgesia, 236cattle, 331, 331dog, 434–5sheep and goat, 346–7, 347Intravenous techniqueaccidents, 529cat, 445, 445–6, 446cattle, 331dog, 398–402, 399, 400catheter insertion, 401intraosseous injection, 401–2vascular port, 402horse, 277–80, 278llama and alpaca, 358–9, 359mouse, 468pig, 372, 372–3, 373rabbit, 466sheep and goat, 349–50, 350Inverted L block, 234, 235cattle, 322sheep and goat, 346Iron therapy, preoperative, 24Isoflurane, 11, 140–1, 142blood pressure response, 12paediatric patients, 39caesarean sectionbitch, 489cattle, 486horse, 486sow, 488cardiovascular effects, 12, 135,412–14horse, 268drug interactions in dog, 392expiratory reserve volume (ERV)effect, 181eye movements, 33general anaesthesiabear, 475bird, 474, 475cardiopulmonary bypass, 503cat, 458cattle, 336–7chelonia, 470deer, 362dog, 409, 412–14elephant, 364, 365ferret, 469gerbil, 469guinea pig, 468hamster, 469horse, 297–8, 300llama and alpaca, 360mink, 469monkey, 476pig, 379, 380rabbit, 467rat, 467sheep and goat, 355skunk, 469small mammals, 454snake, 471hepatic damage, 135induction/maintenanceconcentrations, 141

552 INDEXIsoflurane (contd.)inhalation induction infoals, 288minimum alveolar concentration(MAC), 35neuromuscular blocking drugpotentiation, 135, 168obstetric anaesthesia, 484occupational exposure standards,144, 144partition coefficient, 62, 65physicochemical properties,133, 144recovery time, 141respiratory despression, 69total respiratory resistance (RrUsu)effect, 181toxic metabolites, 135Isoprenaline, 527Jackson–Rees system, 211, 457, 459Jamshidi neelde, 402Jaw fracture repair, dog, 428, 428Joint dislocation reduction, 171Jugular venepuncturecat, 446cattle, 332dog, 398, 401, 401horse, 277, 278catheterisation, 278–80, 279llama and alpaca, 358–9, 359sheep and goat, 349–50Jugular venous pressure, 18Ketamine, 104, 114, 128–9aterial blood pressure reponse,12, 39concurrently administeredagents, 128detomidine combination indeer, 362epidural nerve block, 243eye movements/reflexes, 33, 34fentanyl combination inrabbit, 466general anaesthesiabadger, 470bear, 475bird, 472, 473cat, 450, 453cattle, 335chelonia, 470dog, 393, 406guinea pig, 468horse, 286–7, 293, 294, 295mouse, 467, 468pig, 378rat, 467sheep and goat, 352–3small mammals, 465snake, 471stoat, 469weasel, 469obstetric anaesthesia in horse,485, 486occupational exposure hazard, 531premedication agents, 104, 451cat, 454cattle, 331horse, 286, 287sedationmonkey, 476pig, 371side effects, 17, 128management, 81`triple drip’ anaesthesia, 175, 295pig, 378–9wild animal anaesthesia, 477Ketamine/acepromazinecat, 455obstetric anaesthesia, 484sheep and goat, 352Ketamine/benzodiazepinecat, 455caesarean section, 490horse, 295–6small mammals, 465Ketamine/diazepamcaesarean section in sow, 488cardiac catheterisation, 499dog, 425rabbit, 466sheep and goat, 349, 352–3dehorning, 342Ketamine/medetomidine, 87–8cat, 455caesarean section, 490deer, 362dog, 406large Felidae, 460rabbit, 466sheep and goat, 353small mammals, 465Ketamine/xylazine, 87, 128caesarean section in cattle, 486camel, 363cat, 455deer, 362dog, 406elephant, 364large Felidae, 460pig, 378rat, 467sheep and goat, 349, 352–3small mammals, 465Ketoprofen, 92–3dog, 390horse, 255Lack coaxial system, 211–12,212, 409feline anaesthesia, 457Lacrimation, 12, 13Lagomorphs, 465–7, 465inhalation agents, 467intravenous agents, 466postoperative analgesia, 467Laryngeal mask, 172–3Laryngeal muscles, neuromuscularblock sensitivity, 154, 155Laryngeal oedema, 529Laryngeal paralysis, postoperative inhorse, 307Laryngoscope, 221–2, 222, 375apparatus checks, 509Laryngospasm, 12, 511–12prevention in cat, 447–8Laryngotomy tube, 514Lash reflex, 13Lateral saphenous vein injection, dog,398, 400–1, 401Left atrial pressure (pulmonary arterywedge pressure), 46–7Levallorphan, 100Ligand gated channels, 6Lignocaine (lidocaine), 228, 229cardiac arrest, 529cardiac arrhythmias, 499, 523dog, 420caudal block, obstetric anaesthesiain sheep and goat, 486drug interactions in dog, 392epidural analgesiabutorphanol combination, 267cat, 460cattle, 327, 486dog, 431, 432horse, 266, 267, 485obstetric anaesthesia, 485, 486sheep and goat, 342, 343, 345xylazine combination, 267infiltration analgesia, 234intravenous regional analgesiacattle, 331dog, 434–5sheep and goat, 346laryngospasm prevention incat, 447local analgesiacastration in horse, 264cat, 443, 460sheep and goat, 341metabolism, 231obstetric anaesthesia, 484,485, 486paravertebral analgesia inhorse, 265pharmacokinetics, 230, 231specific nerve blockscattle, 320, 329dog, 431horse see Horsesheep and goat, 342, 346systemic/toxic effects, 231–2topical application, 233Lingual arterial pulse, 36, 37Lion, 460Lip mucous membrane colourmonitoring, 39Liver diseasedog, 425, 426drug transport processes, 21intraoperative hypoglycaemia, 57suxamethonium durationprolongation, 166

INDEX 553Liver function, pregnancy-associatedchanges, 482Llama and alpaca, 357–61caudal epidural analgesia, 358endotracheal intubation,359–60, 359general anaesthesia, 358–61inhalation agents, 360–1intravenous agents, 360preparation, 358intravenous techniques, 358–9local analgesia for castration, 358manual restraint, 357peripheral nerve stimulationsites, 160premedication, 358, 360sedation, 360soft palate blockage of posteriornares, 510Local anaesthetic agents, 227–30drug interactions, 233local toxic effects, 233metabolism, 231mode of action, 226–7pharmacokinetics, 230–1structural aspects, 227, 228systemic absorption, 230systemic/toxic effects, 231–3cardiovascular system, 232central nervous system, 231–2respiratory system, 233vasoconstrictor mixtures, 230, 233Local analgesia, 1, 16–17, 225–44accidents, 530–1camel, 363cat, 443, 460cattle, 320–31castration, 326deer, 362dog, 430–6fracture management, 236horse, 91, 257–67, 300castration, 264, 264–5infiltration analgesia, 234–5intraoperative analgesia,91, 300intrasynovial analgesia, 234intravenous regional analgesia(IVRA), 236llama and alpaca, castration, 358muscle tone abolition, 150obstetric anaesthesia, 484pig, 381–3postoperative analgesia, 306pre-emptive analgesia, 5regional nerve blocks, 234, 235sheep and goat, 341–7small mammals, 464spinal nerve blocks see Spinalnerve blockssurface analgesia, 233catheter insertion, 197toxicity, 16see also Epidural analgesiaLocal analgesic cream, 197, 233, 446Lofentanil, 98Lung collapse, 50Lung cysts, congenital, 498Lung ventilators, 187–91characterisitcs, 188–90, 188,189, 190respiratory cycle, 188settings, 191Lung volumesairway resistance relationship,180, 180changes during spontaneousrespiration, 179, 179, 180Magill system, 209–10, 210, 409feline anaesthesia, 457, 459Magill tubes, 219, 220Magnetoencephalography (MEG), 4Malignant hyperthermia, 56porcine, 25, 368–70, 369, 370, 379prevention, 370treatment, 370Malnutrition, 166Mamillary three compartmentmodel, 72, 73Mandibular nerve block, horse, 258,258–9Mannitol, 426Manual IPPV, 187Mapelson classification, 209, 209Marmoset, 476Masseter muscle, neuromuscularblock sensitivity, 154, 155Maxima breathing system, 213Mean arterial pressure (MAP), 39Mean intrathoracic pressure, 183Mean residence time (MRT),non-depolarisingneuromuscular blockingagents, 164, 165Meclofenic acid, 254Medetomidine, 35, 84, 88–90antagonism, 91cattle, 319atipamezole reversalcat, 444llama and alpaca, 360blood pressure response, 39caesarean section in sow, 487epidural analgesia, 242cattle, 328dog, 432ketamine combination, 87–8, 128cat, 455, 490deer, 362dog, 406large Felidae, 460rabbit, 466sheep and goat, 353small mammals, 465premedication, 124caesarean section in bitch, 488cat, 451cattle, 332dog, 388propofol combination, 296sedationcat, 444cattle, 318dog, 385, 387–9, 416horse, 250llama and alpaca, 360sheep and goat, 348xylazine combination in dog, 398Median arterial pulse, 37Median nerve blockcattle, 330horse, 262, 262Meloxicamdog, 390horse, 255Mental nerve block in horse, 258, 259Meperidine see PethidineMephensin, 174Mepivacaine, 228, 229, 258horseepidural analgesia, 266, 485specific nerve blocks,258, 261metabolism, 231obstetric anaesthesia, 484, 485pharmacokinetics, 230, 231Meptazinol, 94Metatarsal artery, direct bloodpressure measurement, 44Methadone, 97acepromazine combination incat, 450epidural nerve block, 242horse, 256colic, 276Methohexital, 118–19caesarean sectioncat, 490horse, 486general anaesthesiacat, 451–2cattle, 334dog, 403–4horse, 285, 294pig, 377rabbit, 466sheep and goat, 352obstetric anaesthesia, 484Methotrimeprazine, 76, 79etorphine combination, 99sedation/analgesia in dog, 387Methoxamine, 83cardiovascular depression inhorse, 302Methoxyflurane, 140caesarean section in bitch, 488general anaesthesiacat, 458mouse, 468neuromuscular blockpotentiation, 168pharmacokinetics, 66induction speed, 66physical characteristics, 133

554 INDEXMethoxyflurane (contd.)renal damage, 135, 140toxic metabolites, 135Methylprednisolone, 426, 529Metocurine, 165Metomidate, 121–2general anaesthesiahorse, 286pig, 376sedationcaesarean section in sow, 487Midazolam, 82–3ketamine combination, 128cat, 455, 490oxymorphone combination indog, 407premedicationcardiopulmonary bypass,503cat, 451propofol combination for cardiaccatheterisation, 499sedationcat, 445horse, 253sheep and goat, 348sufentanil combination in dog,407–8Middle latency reponse (MLR), 10Minaxolone, 121Minimum alveolar concentration(MAC), 15, 35pregnancy-associated changes,482, 483, 484Minimum infusion rate (MIR), 15Mink (Mustela vison), 469Mitral insufficiency, dog, 423Mivacurium, 164, 173pharmacokinetics, 165Monitoring, 29–57anaesthetic gas analysers, 35,35–6anaesthetic records, 30, 31behavioural/physiologicalparameters, 31blood glucose, 56–7body temperature, 55–6cardiovascular function, 34, 36,36–48cattle, 337–8central nervous system, 31, 33,33–4, 34dog, 418, 428equipment checks, 57, 509equipment maintenance, 29horse, 281initiation, 30levels, 31, 32neuromuscular blockade, 57,155–61preoperative sedation, 30–1recovery period, 31respiratory rate, 34respiratory system, 48–55sheep and goat, 354, 356–7urine volume, 56Monkeyfluid therapy, 470–1general anaesthesia, 475–6handling, 475postoperative care, 477sedation, 476Morphine, 94, 95, 96acepromazine combinationcat, 442, 450dog, 398cat, 442diazepam combination indog, 495epidural analgesia, 96, 241dog, 428, 430, 431, 433, 434horse, 257sheep and goat, 346, 357horse, 256, 257, 300colic, 276intra-articulardog, 428, 434horse, 257pontine reticular formationactions, 7–8postoperative analgesiacaesarean section, 487, 491cat, 459, 491diaphragm rupturerepair, 497sheep and goat, 487premedicationcaesarean section in bitch, 487cardiopulmonary bypass, 503protein-bound transport, 21side effects, 25Mouse, 467–8, 468physiological measurements, 464Mouth examination, preoperative, 19Muscle blood flow, horse, 273, 274Muscle relaxants see Neuromuscularblocking agentsMuscle tone, 149depth of anaesthesia assessment,12, 31Musculocutanoues nerve block,horse, 262–3Myasthenia gravis, 168–9Myelin sheath, 225, 226Myelography, 425–6Myocardial sensitization tocatecholamines, 135, 429Myopathy see PostanaestheticmyopathyNalbuphine, 100Nalorphine, 93, 101Naloxone, 93, 94, 95, 101, 103, 288,516–17obstetric anaesthesia reversal,483, 485puppies, 487–8Naltrexone, 101, 510Naproxencontraindication in cat, 443dog, 393Needles, 197intravenous techniques in horse,277, 278occupational hazards, 531small vein, 200, 200Negligent delegation to assistant, 2Neostigmine, 152, 169, 170–1, 304atropine neutralization ofmuscarinic effects, 105dog, 418overdosage, 25Nephrotoxicity, 22, 414inhalation anaesthetics, 135Nerve block, 226–7Nerve fibres, 225–6diameter-function relationship,226, 226Nerve growth factor, 2Neuroleptanalgesia, 101, 101–2,102, 104cat, 442dog, 397, 398, 407–8, 425small mammals, 465Neuroleptics, 75, 76opioid combinations seeNeuroleptanalgesiaNeurologic disease, dog, 425–7, 427intracranial pressure elevation,426myelography, 426–9Neuromuscular blocking agents,149–75antibiotics potentiation, 275,392, 417caesarean sectionbitch, 490sow, 487cardiac catheterisation, 499cardiopulmonary bypass, 503cat, 459endotracheal intubation,445, 446cattle, 337centrally acting agents, 149–50,174–5, 191clinical use, 171–4contraindications, 172indications, 171–2technique, 172–4depolarising agents, 153, 154,165–8phase II block, 153, 157, 169dog, 416–18, 417termination of block, 417–18drug interactions, 168electrolyte interactions, 169evoked recovery, 169–71factors determining response,168–9horse, 302–5termination of block, 304–5hypothermia effects, 168, 174inhalation anaestheticpotentiation, 135

INDEX 555laryngeal spasm management, 512monitoring, 57, 155–61clinical evaluation of residualparalysis, 159muscle sensitivity, 154–5acetylcholine receptornumber/density, 154muscle fibre size, 154perfusion factors, 154–5respiratory muscles, 154non-depolarising (competitive)agents, 153, 154, 161–4pharmacokinetics, 164–5obstetric anaesthesia, 484, 485pig, 380–1, 381postoperative complications, 174sensitivity with neuromusculardisease, 168–9ventilatory support, 154reversal for weaning, 191Neuromuscular disease,neuromuscular blocksensitivity, 168–9Neuromuscular junctionacetylcholine nicotinic receptors,151, 152, 152desensitisation, 152–3end plate ion channel block, 152presynatpic acetylcholinereceptors, 152receptor-gated ion channels,151–2Neuromuscular transmission, 149,150–3receptor-gated ion channels, 151–2Neuropathy, postanaesthetic in horse,273, 274–5, 275Nitric oxide synthase inhibitors, 243Nitrous oxide, 136–7analgesia, 136, 137aterial blood pressure reponse, 12delivery apparatus, 205–6diffusion hypoxia, 66, 137gas cylinders, 205general anaesthesiacardiopulmonary bypass, 503cat, 457cattle, 337dog, 409, 410, 414–15horse, 299monkey, 476pig, 380rabbit, 467sheep and goat, 355inhalation agent flammabilityinfluence, 134intravenous anaesthesia (IVA), 114neuromuscular blocking drugpotentiation, 135obstetric anaesthesia, 484occupational exposure standards,144physical characteristics, 133potency, 67respiratory despression, 69second gas effect, 136–7, 409vaporizer administration, 67–8NMDA antagonistsepidural nerve block, 243pre-emptive analgesia, 5Nociceptin (orphanin FQ), 3–4Nociceptors, 2Nocistatin, 4Nodes of Ranvier, 225, 226Non-inflammability, 133–4Non-rebreathing systems, 209–13coaxial systems, 211–12, 212flow rates, 213Magill system, 209–10, 210Mapelson classification, 209,209modifications, 212–13T-piece system, 210–11, 211Noradrenaline, 3, 83adrenoceptor interactions, 6local anaesthetic mixtures, 230neuromuscular transmissionactions, 152Norman system, 409NSAIDs (non-steroidal antiinflammatorydrugs), 22,91–3cat, 442, 442–3COX 2 sparing agents, 255dog, 390–1, 428epidural injection, 243horse, 254–5, 281, 300, 306colic, 276, 277pharmacokinetics, 255side effects, 255mode of action, 91postoperative pain relief, 6, 306Nutrition, preoperative in horse, 275Nystagmus, 13, 33Obstetric anaesthesia, 481–91cat, 490–1cattle, 486dog, 487–9goat, 486–7horse, 484–6pig, 487–8sheep, 486–7Obstructive pulmonary disease,chronic (COPD), 181Occupational exposure, 531inhalation anaesthetics, 139, 144,144–5, 531Large Animal Immobilon, 288standards, 537halothane, 144, 144Oculocardiac reflex, 103Oedema, preoperative, 18Oesophageal stethoscope, 36, 37–8Oesophageal surgery, 496‘Omnopon’, 96‘Omnopon-Scopolamine’, 96Open breathing systems, 208–9Operating table, horse positioning,291–2, 291Opioid analgesics, 35, 93–6, 95acepromazine combination,cat, 450agonists, 94, 96–9antagonists, 93, 101, 510–11aterial blood pressure reponse, 12cat, 442, 441, 450, 459–60clinical actions, 94–5dog, 397–8, 418–19, 418, 422, 423,430, 431–2, 433epidural analgesia, 96, 150, 241–2detomidine combination, 257dog, 431–2, 433horse, 257, 267postcaesarian section in sheepand goat, 487horse, 255–7, 256, 267, 281, 300, 485colic, 276intra-articular, 257intraoperative, 95dog, 418–19, 430horse, 300obstetric anaesthesia, 483, 485horse, 485partial agonists, 94, 95, 99–100use as antagonists, 101postoperative analgesiacat, 459–60dog, 422, 423monkey, 477sheep and goat, 357pre-emptive analgesia, 5premedicationdog, 397–8horse, 281sheep and goat, 349receptor specificity, 93–4, 93sedationdeer, 361, 362sheep and goat, 348–9sedative combinations, 101–3horse, 253–4, 254sequential analgesia, 100–1sheep and goat, 348–9, 357, 487side effects, 93, 95respiratory depression, 93, 94,95, 516vomiting, 30, 76, 80Opioid receptors, 3, 93–4endogenous ligands, 93stimulation effects, 94Organophosphate insecticide-druginteractions, 445ORL-1 (opioid receptor-like)receptor, 3Orphanin FQ (nociceptin), 3–4Orthopaedic surgery, dog, 428, 428–9Oscillometric blood pressuremeasurement, 42, 42–4Ostrich, 475Oxygen availability, 51cardiac output relationship,19–20, 51Oxygen cylinders, 202pin-indexed fittings, 202

556 INDEXOxygen deliveryequipment checks, 57, 508hypoxaemia, 517–18warning devices, 205Oxygen partial pressure (PaO 2 ), 49,49, 50Oxygen saturation (SaO 2 ),49, 51pulse oximetry, 51, 52Oxymorphoneacepromazine combination indog, 398diazepam/midazolamcombination in dog, 407, 425epidural analgesia, 96, 242dog, 431–2, 433, 434Oxytocin, 483bitch, 489horse, 486sow, 488Pacemaker insertion, 505, 505Pacing, external, 527Paediatric patientsarterial blood pressure, 39blood volume assessment, 48general anaesthesiakittens, 459puppies, 394, 394hypoglycaemia, 56hypothermia, 528inhalation induction in foals,288–9neuromuscular blockresponse, 168Pain, 2–6afferent mechanisms, 2–3central processes, 3–4functional imaging, 4–5control, 5–6definition in animals, 5evaluation, 422Palmar/plantar nerve block, horse,260–2abaxial sesamoid injectiontechnique, 260–1, 261indications, 262metacarpal/metatarsal injectiontechnique, 261terminal digital nerves, 261–2Palpebral reflex, 13, 33Pancuronium, 162, 173cattle, 337dog, 417, 417horse, 304inhalation agent potentiation,168obstetric anaesthesia, 485pharmacokinetics, 165train-of-four (TOF) stimulationresponse, 157verapamil interaction, 152Papaveretum, 96acepromazine combination, 96cat, 450hyoscine combination, 96, 106dog, 397premedicationcaesarean section in bitch, 487cardiopulmonary bypass, 506Paravertebral block, 150cattle, 322–5, 323, 324caesarean section, 486horse, 265, 265obstetric anaesthesia, 484sheep and goat, 346caesarian section, 486, 487Partial pressure (tension), 61Partition coefficient, 61–2inhaled anaesthetics, 65Patent ductus arteriosus, dog, 423–4Pedal reflex, 33–4Penicillin, 275Pentazocine, 95, 100horse, 256sequential analgesia, 100Pentobarbital, 104, 126–7clinical role, 127depth of anaesthesia, 34general anaesthesiacat, 452cattle, 334–5dog, 404pig, 377–8sheep and goat, 352small mammals, 465intratesticular injection in pig, 378sedation in cattle, 320Peribulbar nerve block, cattle, 321–2Pericarditis, 498Peripheral arterial palpationblood pressure estimation, 40pulse, 36, 37, 37Peripheral nerve block, 150Peripheral nerve stimulation,155–61, 156double burst stimulation (DBS),158, 158hypothermia effect, 160muscle twitch appraisal, 158–9overstimulation, 160–1single twitch, 156stimulation sites, 159–60tetanus, 157–8train-of-four (TOF), 156–7, 156, 157Peroneal nerve blockcattle, 330, 330horse, 263, 263sheep and goat, 347, 347Petersen eye block, cattle, 321, 321, 322Pethidine, 96–7, 100acepromazine combinationcat, 442dog, 398cat, 442epidural nerve block, 241horse, 256colic, 276postcaesarean section analgesiacat, 491cow, 486sheep and goat, 487postoperative analgesiacat, 459diaphragm rupturerepair, 497rabbit, 467rat, 467sheep and goat, 357sheep and goat, 348, 357, 487pH, arterial blood, 49, 49Phaeochromocytoma, 55Pharmacodynamics, 61–74, 62definitions, 61Pharmacokinetics, 61–74, 62definitions, 61inhaled anaesthetics, 63–9intravenous anaesthetics, 69,69–74local anaesthetics, 230–1non-depolarising neuromuscularblocking agents, 164–5, 165pregnancy-associated changes,476Phencyclidine, 127sedation in pig, 371Phenothiazines, 12, 75, 76, 76–9antiemetic actions, 76horse, 247–8opioid combinations(neuroleptanalgesia), 101premedication, 103–4cat, 450dog, 397sedationcat, 443dog, 385–7side effects, 76Phenylbutazone, 92dog, 390drug interactions, 25endotoxic shock, 521horse, 254, 255Phenylephrine, 83, 302local anaesthetic mixtures, 230Physiological dead space:tidalvolume ratio, horse, 271Pig, 367–83airway management, 368, 368caesarean section, 487–8castration, 382–3intratesticular anaesthesia, 378endotracheal intubation,374–5, 374epidural analgesia, 381, 381–83general anaesthesia, 367, 371–81inhalation agents, 379–80intravenous agents, 376–9premedication, 371–72preparation, 371recovery, 368intramuscular injection, 368intraperitoneal injection, 373–4intravenous technique, 372–3,372, 373

INDEX 557laryngeal spasm, 511local analgesia, 381malignant hyperthermia, 25,368–70, 369, 370, 379neuromuscular blocking agents,167–8, 378–9, 381obstetric anaesthesia, 487–8pleural cavity drainage, 495regurgitation, 513respiratory problems, 376, 510restraint, 367–8, 367, 370sedation, 370–1Pinna stimulation, 13Pipecuronium, 163pharmacokinetics, 165train-of-four (TOF) stimulationresponse, 157Pipeline systems, 205Placental drug transfer, 482–3α 2 adrenoceptor agonists, 484neuromuscular blockingagents, 485opioids, 483, 485Plantar nerve blockhorse see Palmar/plantar nerveblock, horsemetatarsal block in cattle,329, 330Plateau principle, 72Plenum vaporiser, 206Pleural cavity drainage, 493–5, 494Pneumothoraxintermittent positive pressureventilation (IPPV),184–5, 185cardiovascular responses, 186mediastinal movement,185–6paradoxical respiration,185, 185see also Intrathoracic surgeryPolymixins, 392Porphyria, 118Portosystemic shunt, 57Position for operation, 529horse, 290–2, 291, 292, 293Positive end-expiratory pressure(PEEP), 191–2horse, 272Positron emission tomography(PET), 4Postanaesthetic myopathy(rhabdomyolysis), 39, 40horse, 272, 273–4treatment, 274Postoperative analgesia, 5–6caesarean sectionbitch, 490cat, 484cow, 486sheep and goat, 487cardiopulmonary bypass, 504cat, 459–60, 490diaphragm rupture repair, 497dog, 423, 422–3, 490horse, 306monkey, 477pain evaluation, 422pre-emptive analgesia, 5pulmonary surgery, 498rabbit, 467rat, 467sheep and goat, 357, 487small mammals, 465Postoperative carecat, 459–60dog, 420–3Potency, inhaled anaesthetics, 67Power spectrum analysis,electroencephalography(EEG), 9, 9–10, 10Preanaesthetic preparation, 22–4cat, 439diabetes mellitus, 24dog, 391–96auscultation of thorax, 397–8fluid and electrolyte balance, 23food and water intake, 22–3haemoglobin, 24horse, 275–6colic, 276llama and alpaca, 358pig, 371sheep and goat, 349small mammals, 463see also Preoperative evaluationPre-emptive analgesia, 5, 91Pregnancy, 481–2circulation changes, 481–2, 483drug actions, 483–4drug disposition, 482–3liver function, 482local analgesia, 484renal function, 482respiratory system changes,482, 483uterine blood flow, 482Premature ventricular contractions,38–9Premedication, 17, 106–7aims, 106α 2 adrenoceptor agonists, 104analgesic agents, 106anticholinergic agents, 103anxiolytic drugs, 103arterial blood pressureresponse, 39caesarean section in bitch, 487cardiopulmonary bypass, 503cat, 441, 443, 444, 449–50dog, 386–7, 390, 396–8, 397, 487drug selection, 75–6elephant, 364horse, 280–1, 285llama and alpaca, 358, 360monitoring, 30–1pig, 371–2sedatives, 103–4, 124sheep and goat, 349small mammals, 464Preoperative evaluation, 17–19biochemical tests, 19cardiovascular function, 17–18,19–20renal function, 18, 19, 21–2respiratory function, 18–19,19–20see also Preanaesthetic preparationPressure gauges, 202, 203Pressure reducing valves/regulators,203, 205Prilocaine, 228, 229pharmacokinetics, 230Primates, non-human, 475–7see also MonkeyProcaine, 227, 228metabolism, 231topical application, 233Projectile syringes, 477–8, 478Promazine, 76, 79sedation/analgesia in dog, 389Promethazine, 76, 79, 529Propionylpromazine, 76, 79premedication in cat, 450sedation/analgesia in dog, 389Propofol, 114, 123–5caesarean sectionbitch, 488cat, 489cattle, 486sow, 488cardiopulmonary bypass, 503cat, 451, 453, 490cattle, 336, 486clinical applications, 124–5continuous infusion, 405, 405dog, 393, 404–5disposition, 124, 124eye movements, 33horse, 285–6, 296–7llama and alpaca, 360mean utilization rate, 124, 124medetomidine combination, 296midazolam combination forcardiac catheterisation, 499obstetric anaesthesia, 484pharmacokinetics, 69, 70, 74recovery, 124, 125sheep and goat, 354dehorning, 341small mammals, 465xylazine combination, 296Propoxate hydrochloride, 472Protein-bound drugs, 20–1Pruritus, 233Pseudocholinesterase, 231Pudic (internal pudendal) nerveblock, cattle, 325–6, 324Pulmonary artery wedgepressure see Left atrialpressurePulmonary disorders, preoperativeevaluation, 18, 19–20Pulmonary surgery, 497–8postoperative analgesia, 498

558 INDEXPulse oximetry, 50–3, 51, 507, 508dog, 418, 428horse, 281reflectance probes, 52–3sites, 52Pupil size, 13Pyridostigmine, 169, 170, 171Quantiflex system, 205Rabbit (Oryctolagus cuniculus),465–67, 466physiological measurements, 464Rat, 467, 467physiological measurements, 464postoperative analgesia, 465Ratites, 475Rebreathing systems, 213–18carbon dioxide absorption, 213–14circle system, 215–16, 410to-and-fro system, 214–15,215, 409dog, 409vaporiser location, 216–18Records, anaesthetic, 30, 31Recovery from anaesthesiacat, 459, 460cattle, 338elephant, 365horse, 306–7inhaled anaesthetics, 66pig, 368sheep and goat, 357Recumbencycattle, associated problems,315, 316horseassociated problems, 268, 270,271, 273intraoperative positioning,290–2, 291, 292, 293Referred pain, 2Reflexes, depth of anaesthesiamonitoring, 31, 33–4Regional nerve blocks, 234, 235Remifentanil, 98Renal diseasedog, 429, 429intraoperative dehydration, 21,22, 23preoperative evaluation, 18, 19,21–2thiopentone use, 117–18Renal failure, acute, 21dog, 429intraoperative hypotension, 39intrinsic, 22postrenal (obstructive), 22prerenal, 21Renal function, pregnancy-associatedchanges, 482Reptilia, 470–1ketamine sedation, 129Reserpine, sedation in horse, 253Respiratory acidosis, 518Respiratory depression, 516blood gas tensions, 50inhaled anaesthetics, 69opioid analgesics, 93, 94, 95, 516respiratory rate, 48Respiratory functiondepth of anaesthesia assessment,12, 31, 33pregnancy-associated changes,482, 483recumbency-associated problemsin cattle, 316spontaneous respiration, 179,179–82pressure changes, 180, 180Respiratory minute volumedepth of anaesthesiaassessment, 12monitors, 49Respiratory muscle responses, 12Respiratory obstruction, 49, 509–10Respiratory ratedepth of anaesthesia assessment,12, 13, 34monitoring, 48–9Respiratory sounds, preoperativeevaluation, 18–19Respiratory stimulants, 517Respiratory system impedence, 181Respiratory system monitoring, 48–55acid-base status, 54–5arterial pH/blood gas tensions,49–50, 49capnography, 53–4, 53pulse oximetry, 50–3, 51respiratory rate, 48, 49tidal volume, 49Respiratory system reactance, 181Respiratory system resistance, 181intermittent positive pressureventilation (IPPV), 183Restraint, 1, 2Resuscitationanaphylaxis/anaphylactoidreactions, 529cardiac arrest, 524, 524–7emergency equipment, 527–8Reticular formation, 7Retrobulbar nerve block, cattle, 321–2Revivon, 102, 103, 516Large Animal Immobilonreversal, 287–8Rhabdomyolysis, postanaesthetic seePostanaesthetic myopathyRocuronium, 163dog, 416inhalation agent potentiation, 168pharmacokinetics, 165train-of-four (TOF) stimulationresponse, 157Rodents, 463–5, 467–8analgesia, 465general anaesthesiainhalated agents, 464intravenous agents, 464–5handling, 463, 464local analgesia, 464physiological measurements, 464preanaesthetic preparation, 463premedication, 464respiratory problems, 463, 464volume replacement, 464Romifidine, 84, 90dog, 390horse, 250, 251acepromazine complications,253butorphanol combination, 254premedication, 280–1, 285, 286sheep and goat, 348Ropivacaine, 230Rotameters, 203, 203Rowson laryngoscope, 375Safety aspects, 1, 531see also Occupational exposureSaffan, 119–21caesarean section in cat, 490dehorning in sheep and goat, 342general anaesthesiabird, 474cat, 452–3, 490chelonia, 470dog, 408monkey, 475, 476pig, 370, 378rabbit, 466sheep and goat, 342, 353–4small mammals, 463stoat, 469weasel, 469histamine release-mediated sideeffects, 119–20obstetric anaesthesia, 484sedation for closure of chest, 495Salicylate, 91–2Salivation, 103, 172cattle, 316depth of anaesthesiaassessment, 13pig, 369sheep and goat, 355–6Saphenous nerve block, horse, 263Saphenous vein puncture, sheep andgoat, 349Scavenging system, 531apparatus checks, 509Second gas effect, 69, 136–7, 409Second messengers, 6Sedation, 2, 75, 76–91α 2 adrenoceptor agonists, 83–90α 2 adrenoceptor antagonists,90–1benzodiazepines, 80–3butyrophenones, 79–80cardiopulmonary bypass, 503cat, 443–5, 450, 495premedication, 450–1cattle, 317–20deer, 362

INDEX 559dog, 385–9, 386, 495drug selection, 76horse, 247–54obstetric management, 485premedication, 280–1monkey, 476phenothiazines, 76–9pig, 370–1caesarean section, 487pleural cavity drainage, 495sheep and goat, 348–9caesarian section, 486Sedativesdefinition, 75opioid combinations, 101–3premedication, 103–4Seizures, local anaesthetic toxicity,231–2, 233Seldinger technique, 198–9, 280Semi-open breathing systems, 208–9Septicaemia, 57Sequential analgesia, 100–1Sevoflurane, 143, 143–4aterial blood pressure reponse, 12caesarean section in bitch, 488cardiovascular effects, 412–14horse, 268chemical stability/decompositioncompounds, 134, 144compound A, 414general anaesthesiacat, 458cattle, 337dog, 409, 412–4, 489horse, 298pig, 379, 380sheep and goat, 355inhalation induction in foals, 288minimum alveolar concentration(MAC), 35obstetric anaesthesia, 484partition coefficient, 65physicochemical properties,133, 144Sheep and goat, 341–57caesarian section, 486castration, 342caudal block, 342–3, 343, 486endotracheal intubation,350–1, 351epidural analgesia, 343, 344, 344–6general anaesthesia, 349–57fluid therapy, 356inhalation agents, 355intravenous agents,351–5, 353monitoring, 356, 356–7positioning, 355–6preparation, 349recovery, 357intravenous regional analgesia,346–7, 347intravenous technique, 349–50, 350local analgesia, 341–7obstetric anaesthesia, 486–7pleural cavity drainage, 495postoperative analgesia, 357sedation, 348–9specific nerve blockscornual, 341–2, 342digital nerves, 343inverted L, 346paravertebral, 346peroneal, 347, 347tibial, 347, 347suxamethonium sensitivity, 167Shock, 520–1Single photon emission computedtomography (SPECT), 4Single twitch stimulation, 156Sinus arrhythmias, 38, 39Skunk (Mephitis mephitis), 469Sleep, 7–8Small mammals, 463–70analgesia, 463general anaesthesiainhalated agents, 464injectable agents, 464–5handling, 463, 464hypothermia, 528local analgesia, 464monitoring, 463neuroleptanalgesia, 465physiological measurements, 464preanaesthetic preparation, 463respiratory problems, 463, 464volume replacement, 464Small vein set, 200, 200Snake, 470–1, 471respiratory tract, 470Snell infla-table, 291Soda lime, 57, 68, 134, 142, 213–14compound A generation fromsevoflurane, 414see also Carbon dioxide absorptionSolubilitycoefficient, 61–2inhaled anaesthetics, 64, 64–5induction speed, 66overdosage, 66Somatosensory evoked responses(SER; SEP), 11Somatostatin, epidural injection, 243Spinal malacia, 275Spinal nerve blocks, 236–44bradyarrhythmias management,522drugs, 241–3effects, 239–40cardiovascular, 239, 240epi- (extra-)dural injection, 236–9caudal block, 240–1epidural block, 241subarachnoid injection, 236Spinothalamic tracts, 2Squeeze cages, 477Squirrel monkey, 476Status epilepticus, 82Stephens machine, 409Sterilisation of apparatus, 222Stoat (Mustela erminae), 469Streptomycin, 392Stress responses, drugmetabolism, 20Subarachnoid anaesthesia, 236horse, 267Sublingual vein injection, dog, 398,401Sufentanil, 98epidural analgesia, 96, 242dog, 432midazolam combination indog, 407–8Supraorbital nerve blocks, horse,258, 259Supraventricular arrhythmias, 520Surface analgesia, 239Suxamethonium, 165, 166–8anticholinergic cover, 103cat, 447, 448, 459clinical use, 172, 173dog, 416, 417drug interactions, 25, 168organophosphate insecticides,445genetic factors in response, 169horse, 304monkey, 476muscle fasiculation, 166phase II block, 153pig, 380–1endotracheal intubation, 375malignant hyperthermia, 368species sensitivity differences,166, 167train-of-four (TOF) stimulationresponse, 157Suxethonium, 165Sweating, 12Synapsin I, 152Synaptic transmission, 6, 7fast/slow signalling, 6general anaesthetic agent actions,6–8second messengers, 6see also NeuromusculartransmissionSyringe drivers, 201, 201, 405, 405Syringes, 197occupational hazards, 531Systolic arterial pressure (SAP), 39T-piece system, 210–11, 211, 409bird, 474cat, 457, 459Jackson-Rees modification, 211,457, 459rabbit, 467small mammals, 464Tachycardia, 12preoperative evaluation, 18Tameridone, 91Tension (partial pressure), 61Terapins, 470Tetanic fade, 151

560 INDEXTetanic peripheral nerve stimulation,157–8Tetanus prophylaxis, 275Tetracaine, 228metabolism, 231Tetracyclines, 392Thalamic pain centres, 2Thiamylal sodium, 118Thiopental (thiopentone), 114, 115–18accidental perivascularinjection, 529caesarean sectionbitch, 488cat, 489cattle, 486horse, 486sow, 487, 488contraindications, 118eye movements, 33general anaesthesiacamel, 363cardiac catheterisation, 499cat, 451, 490cattle, 331, 333–4dog, 393, 402–3, 488horse, 283–5, 284, 293,294, 486large Felidae, 460monkey, 475pig, 376–7, 487rabbit, 466sheep and goat, 352small mammals, 465guaiphenesin combination incattle, 331, 334liver damage, 117liver metabolism, 116obstetric anaesthesia, 484plasma pH effects, 115–16presentation, 118protein binding, 20respiratory depression, 116–17Thoracotomy, 496cardiac arrest, 526dog, 429–30, 429intercostal nerve block, 433–4intrapleural analgesia, 434pulmonary surgery, 497–8Thyrotoxicosis, 55Tibial nerve blockcattle, 330horse, 263, 263sheep and goat, 347, 347Tidal volumedepth of anaesthesiaassessment, 12monitors, 49Tiger, 460Tiletamine, 127aterial blood pressure reponse, 39induction in horse, 287postoperative hyperthermia, 56zolazepam combination,127–8, 445cat, 455, 455–6cattle, 337dog, 406–7sheep and goat, 353Tilting table control method,282, 283Tissue perfusion monitoring, 36, 39Tissue solubility, 62To-and-fro carbon dioxide removalsystem, 214–15, 215, 409Tolazoline, 90, 91sedation reversalcattle, 318–19sheep and goat, 348Tortoise, 470Total apparent volume of distribution,69–70Total elimination clearance(Cl E ), 70Total intravenous anaesthesia(TIVA), 114horse, 283–8, 284, 292–7Total respiratory resistance (RrUsu),180, 181, 181Total spinal block, 244Total thoracic compliance, 182Toxaemia, 17Toxicityindividual/species variation, 17inhalation anaesthetic metabolites,134–5Tracheostomy, 513–14Tracheostomy tube, 513–14, 514Train-of-four (TOF) stimulation, 156,156–7, 157Tranquillizers (ataractics), 75Transpulmonary pressure, 179, 179Tricaine methanesulphonate, 471–2Trichloroethylene, 379Trimeprazine, 388`Triple drip’ anaesthesia, 175, 295pig, 378–9d-Tubocurarine, 161dimethyl ether, 161horse, 304hypercapnia potentiation, 168inhalation anaestheticpotentiation, 135mode of action, 152protein-bound transport, 21Tuohy needle, 343, 343, 345, 432Turtle, 470Ulnar nerve blockcattle, 329horse, 262, 262Ultrasonography, cardiac surgery, 499Urethane, 126Urine testing, preoperative, 19Urine volume monitoring, 56Uterine blood flow, 482Uterine involutionbitch, 488cow, 480horse, 486sow, 488Vagus-mediated bradycardia,103, 104Vaporisers, 67–8, 206–8apparatus checks, 508–9calibrated, 206–7inside breathing circuit, 216–17low resistance, 207–8occupational safety, 531outside breathing circuit,217–18uncalibrated, 206Vascular port, dog, 402Vasculogenic shock, 520Vasodilator therapy, 521Vasopressin, epiduralinjection, 243Vd C , 164, 165, 165Vecuronium, 162–3, 173dog, 417, 417drug interactions, 392horse, 304obstetric anaesthesia, 485pharmacokinetics, 165train-of-four (TOF) stimulationresponse, 157Vedaprofen, 255Venous access, 198Venous admixture, horse, 271Ventilators, apparatuschecks, 509Ventricular arrhythmias, 522–3dog, 420, 420Ventricular extrasystoles, 522Ventricular fibrillation, 522, 523hypothermia response, 500Verapamil, 392, 522pancuronium interaction, 152Volatile anaesthetic agents seeInhalation agentsVoltage gated channels, 6, 7Volumetric (constant infusion)pumps, 200, 201Vomiting during induction, 512Warfarin, 25Wasting diseases, 17Water access, preoperative, 23Water blanket, 528, 528Water mattress, 291Weaning from IPPV, 191Weasel (Mustela nivalis), 469Weight estimationelephant, 363horse, 277, 277Whisker reflex, 34Wild animals, 477–8Wright’s respirometer, 49Xylazine, 39, 75, 83, 84, 86–7camel, 363cat, 443–4cattle, 317–18, 332tiletamine/zolazepamcombination, 336caudal injection, 252

INDEX 561deer, 362, 363dog, 387, 432medetomidine combination,398epidural analgesia, 242cattle, 326–9detomidine/mepivacainecombination in horse, 485dog, 432lignocaine combination inhorse, 267sheep and goat, 345, 346expiratory reserve volume (ERV)effect, 181horse, 248–9, 251, 252, 267,294, 479acepromazine combination, 253colic, 276ketamine combination seeKetamine/xylazinellama and alpaca, 360obstetric anaesthesia, 485, 486opioid combinationsin deer, 362premedicationcaesarean section inbitch, 489cat, 450–1cattle, 331horse, 280–1, 285, 286propofol combination, 296reversal of sedation, 91cattle, 318–19sheep and goat, 346, 348dehorning, 342epidural caesareansection, 345side effects, 87‘triple drip’ anaesthesia, 175, 295pig, 378–9Yohimbine, 83, 90, 517sedation reversalcattle, 318llama and alpaca, 360sheep and goat, 348Zero order processes, 71, 72Zolazepam, 83horseinduction of anaesthesia, 287sedation, 252postoperative hyperthermia, 56tiletamine combination,127–8, 445cat, 445, 455, 455–6cattle, 336dog, 406–7sheep and goat, 353Zygomaticotemporal nerve block,deer, 362