Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 5 ANESTHETIC AGENTS
Table 5.1 Sources of variation in minimum alveolar
concentration (MAC) that occur within a species
Factors that decrease MAC
Hypothermia
Hyponatremia
Pregnancy
Old age
CNS depressants, e.g.
sedatives, analgesics,
injectable anesthetics
Severe anemia
Severe hypotension
Severe hypoxia
Extreme respiratory acidosis
(P a CO 2 > 95 mmHg)
Factors that increase MAC
Hyperthermia
Hypernatremia
CNS stimulants, e.g. amfetamine
intracranial pressure is already raised, e.g. by an intracranial
mass, further increases in pressure may severely
compromise cerebral perfusion and thus oxygen delivery.
Most inhalation anesthetics will also reduce the
metabolic rate and oxygen requirement of the brain and
it is the balance between supply and demand that
governs overall safety.
Cardiovascular effects
All inhalation anesthetics cause dose-dependent depression
of the cardiovascular system. At clinical concentrations
some agents tend to affect the heart more than the
vessels, while for others depression of vascular tone is
the predominant effect. Inhalation agents may also
sensitize the myocardium to catecholamine-induced
arrhythmias. This detrimental effect is influenced by the
chemical structure of the agent, hydrocarbons being
more arrhythmogenic than ethers.
Respiratory effects
All volatile anesthetics depress ventilation in a dosedependent
fashion. As the inspired concentration of
agent is increased, tidal volume falls, followed by reductions
in respiratory rate. These changes lead to retention
of carbon dioxide and the arterial partial pressure of
carbon dioxide (P a CO 2 ) rises accordingly. In the conscious
patient such a change would stimulate increased
ventilation but this reflex is depressed by inhalation
anesthetics. For most agents, respiratory arrest is likely
at alveolar concentrations of between two and three
times MAC. Variations in the degree of respiratory
depression induced by different volatile anesthetics are
relatively small.
Hepatic effects
Mild and transient hepatic dysfunction may be associated
with all the volatile anesthetics, probably as a result
of reduced blood flow and oxygen delivery. More severe
hepatocellular damage occurs rarely and is usually associated
with the use of halothane.
Renal effects
All inhalation anesthetics will reduce renal blood flow
and thus glomerular filtration rate. Direct nephrotoxicity
is a potential adverse effect of those agents that
undergo extensive metabolism to free fluoride ions, e.g.
methoxyflurane.
Skeletal muscle effects
All halogenated volatile anesthetics can trigger malignant
hyperthermia, a potentially life-threatening myopathy
that occurs in susceptible individuals. Susceptibility
is conferred genetically and is most common in rapidly
growing breeds of pig, such as the landrace, large white
and pietrain. However, the syndrome has been reported
in other species, including the dog and cat. It may also
be triggered by stress, and in wild species the term
‘capture myopathy’ has been used.
The mechanism of malignant hyperthermia is not
fully understood but involves a marked elevation in the
concentration of intracellular calcium. This causes
widespread muscle contracture. Lactic acidosis rapidly
ensues as oxygen supply fails to meet demand. The
resultant cell membrane damage leads to electrolyte disturbances,
particularly hyperkalemia, that serve to compound
the problem. Clinical signs include muscle
rigidity, hyperthermia, tachycardia and tachypnea progressing
to dyspnea. The condition is rapidly fatal and
treatment must be instituted at an early stage if it is to
be successful. Inhalation anesthesia should be terminated
immediately and, if available, dantrolene should
be given (2–5 mg/kg IV). This muscle relaxant, which
inhibits the release of calcium from the sarcoplasmic
reticulum, has been used to prevent as well as treat
malignant hyperthermia. Symptomatic treatments
should also be instituted, including aggressive body
cooling, intravenous fluids, ventilation with 100%
oxygen and administration of bicarbonate to correct the
acidosis and hyperkalemia.
Special considerations
Hazards to people
Many adverse health effects, ranging from dizziness and
headaches to spontaneous abortion and congenital
abnormalities, have been attributed to chronic exposure
to waste anesthetic gases, particularly halothane and
nitrous oxide. While experimental studies have largely
failed to confirm this association, measures to minimize
the exposure of operating room personnel to waste
anesthetic gases would seem sensible.
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