Tierärztliche Hochschule Hannover Vergleichende Studie zur

Tierärztliche Hochschule Hannover
Vergleichende Studie zur analgetischen Wirksamkeit
von Inhalationsnarkose sowie Injektions- und
Epiduralanästhesie bei Operationen am Nabel des
Kalbes
INAUGURAL – DISSERTATION
zur Erlangung des Grades einer Doktorin
der Veterinärmedizin
- Doctor medicinae veterinariae -
( Dr. med. vet. )
vorgelegt von
Jennifer Offinger
Memmingen
Hannover 2010

Wissenschaftliche Betreuung:
Univ.-Prof. Dr. Jürgen Rehage
Klinik für Rinder
1. Gutachter: Univ.-Prof. Dr. Jürgen Rehage
Klinik für Rinder
2. Gutachter: Univ.-Prof. Dr. Manfred Kietzmann
Institut für Pharmakologie, Toxikologie
und Pharmazie
Tag der mündlichen Prüfung: 01. November 2010
Eine Arbeit mit Unterstützung durch die Konrad-Adenauer-Stiftung e.V.

Meinen Eltern

Jennifer Offinger
Vergleichende Studie zur Analgesie der Nabelregion mittels Isofluran-
Inhalationsnarkose, Epiduralanästhesie und Injektionsnarkose und zu den
Auswirkungen dieser drei Methoden auf die intraoperativen Schmerzparameter und
das Herzkreislaufsystem bei Kälbern
Inhaltsverzeichnis
Einleitung und Fragestellung der Arbeit...................................................................... 1
Literatur................................................................................................................. 9
Publikation 1:............................................................................................................ 15
Percutaneous, ultrasonographically guided technique of catheterization of the
abdominal aorta in calves for serial blood sampling and continuous arterial blood
pressure measurement
Publikation 2:............................................................................................................ 17
Comparison of isoflurane inhalation anaesthesia, injection anaesthesia and high
volume caudal epidural anaesthesia in calves; metabolic, endocrine and
cardiopulmonary effects
Publikation 3:............................................................................................................ 56
Case report: Spinal chord infarct in a calf after aortic catheter implantation............
Übergreifende Diskussion......................................................................................... 75
Literatur............................................................................................................... 83
Zusammenfassung ................................................................................................... 86
Summary .................................................................................................................. 89
Danksagungen ......................................................................................................... 92
I

Abkürzungsverzeichnis
A.a.
a
Abb.
ABP
ACTH
AD
AMG
AMV
BE
BW
˚C
C a O 2
CcO 2
CI
C v¯ O 2
cm
CO
D oder d
E
Fig.
g
h
Hb
HCO 3
HPA
HR
ID
Aorta abdominalis (Abdominal aorta)
arteriell (arterial)
Abbildung
arterial blood pressure
Adrenocorticotropes Hormon
Außendurchmesser
Arzneimittelgesetz
Atemminutenvolumen
Basenüberschuss (base excess)
body weight
Grad Celsius
Arterieller Sauerstoffgehalt (arterial oxygen content)
Sauerstoffgehalt in Lungenkapillarblut (oxygen content in
pulmonary capillary blood)
Herzindex (cardiac index)
Gemischt venöser Sauerstoffgehalt (mixed venous oxygen
content)
Zentimeter (centimetres)
Herzzeitvolumen (cardiac output)
Tag (day)
Epinephrin (epinephrine)
Figure
Gramm
Stunden (hours)
Hämoglobin (haemoglobin)
Standard-Bikarbonatgehalt
hypothalamo-hypophysär-andrenerges System
Herzfrequenz (heart rate)
Innendurchmesser (inner diameter)
II

I.E.
internationale Einheit
IM oder i/m intramuskulär
I.U.
international units
IV oder i/v intravenös
kg
Kilogramm
KGW
Körpergewicht
kPa
Kilopascal
L
Liter
MAP
arterieller Mittelduck (mean systemic arterial pressure)
MCVP
zentralvenöser Mitteldruck (mean central venous pressure)
mg
Milligramm
min
Minute
mL
Milliliter
mm
Millimeter
mmHg
Millimeter Quecksilbersäule
mmol
Millimol
MPAP
pulmonalarterieller Mitteldruck (mean pulmonary artery pressure)
µg Mykrogramm
n
Anzahl
NaCl
Natriumchlorid
NE
Norepinephrin (norepinephrine)
NEFA
freie (nicht veresterte) Fettsäuren (non-esterified fatty acids)
ng
Nanogramm
NRS
Numerisches System (numeric rating scale)
NSAID
nichtsteroidales Antiphlogistikum (non-steroidal antiinflammatory
drug)
O 2
OD
op
P
Sauerstoff (oxygen)
outer diameter
operationem
Irrtumswahrscheinlichkeit (probability)
III

p a CO 2
arterieller Kohlendioxidpartialdruck (arteial partal pressure of
carbon dioxide)
p a O 2
arterieller Sauerstoffpartialdruck (arteial partal pressure of
oxygen)
pAO 2
alveolar oxygen tension
PCWP
pulmonalkapillärer Verschlussdruck (pulmonary capillary wedge
pressure)
PVR
pulmonaler Gefäßwiderstand (pulmonary vascular resistance)
Qs/Qt
pulmonärer Shunt (pulmonary shunt)
RR
Atemfrequenz (respiratory rate)
RQ
respiratorischer Quotient (respiratory quotient)
SD
Standardabweichung (standard deviation)
S a O 2
Sauerstoffsättigung (oxygen saturation)
SC oder s/c subkutan (subcutaneous)
sec
Sekunde (second)
SEM
Standardfehler (standard error of the mean)
SV
Schlagvolumen (stroke volume)
SVR
systemischer Gefäßwiderstand (systemic vascular resistance)
Tab.
Tabelle (Table)
v¯
Gemischt venös (mixed venous)
VAS
Visuell Analoges System (visual analogue scale)
Vol.
Volumen (volume)
vs.
Versus
V E
V T
minute ventillation
tidal volume
% Prozent (percent)
Abkürzungen Gruppen:
INH
Inhalationsanästhesie
EPI
Epiduralanästhesie
INJ
Injektionsanästhesie
IV

Einleitung
Einleitung und Fragestellung der Arbeit
Die Herausforderung in der Anästhesie von Nutztieren liegt darin, praxistaugliche
Medikationen im Rahmen des gültigen Arzneimittelgesetzes (AMG) zu etablieren, die
am Tier einen sicheren und weitgehend schmerzfreien operativen Eingriff
ermöglichen und dabei betriebswirtschaftliche Aspekte nicht aus dem Auge verlieren.
Der Verbraucher legt heute zunehmend Wert darauf, dass Produkte tierischer
Herkunft aus Produktionssystemen stammen, die den Aspekten des „Animal Welfare“
angemessen Rechnung tragen. Hierzu zählt auch eine umfassende
Schmerzausschaltung im Rahmen operativer Eingriffe. Es muss daher auch die
Bereitschaft von Seiten der Landwirte bestehen, Mehrkosten für eine adäquate
Schmerzmedikation ihrer Tiere zu tragen. Umfragen ergaben, dass Landwirte bereit
sind, finanzielle Ressourcen in ein adäquates Schmerzmanagement ihrer Tiere zu
investieren, solange der Markt im Gegenzug die Bereitschaft zeigt, die anfallenden
Mehrkosten für die Fleisch- und Milchproduktion zu übernehmen. Die Bereitwilligkeit,
in Verbesserungen des Wohlbefindens der Tiere zu investieren, wurde zwar durch
Konsumentenumfragen deutlich signalisiert, jedoch reflektiert das Kaufverhalten der
Konsumenten jene Werte, die von diesen Studien abgeleitet werden, nicht wider
(Moran and McVittie, 2008).
Durch den Druck des internationalen Wettbewerbes ist die Wirtschaftlichkeit nach wie
vor der entscheidende Faktor in modernen Produktionssystemen. Oftmals rechtfertigt
1

Einleitung
der geringe Wert des Einzeltieres nicht den Gebrauch kostspieliger Medikamente
und die Anschaffung von teuren Apparaturen wie Narkosetowern, OP-Tischen und
Überwachungsgeräten. Anästhesieverfahren müssen einfach, ökonomisch, risikoarm
und wirksam sein. Es liegt in der Verantwortung der Forschung, den Praktikern
wissenschaftlich fundierte Anästhesietechniken aufzuzeigen, die ein verantwortbares
Maß an Ökonomie, Praktikabilität und Sicherheit vereinen und dabei auch ethischen
Anforderungen gerecht werden.
Wesentlicher Bestandteil einer Anästhesie ist das Ausschalten des
Schmerzempfindens (Analgesie) sowie nozizeptiv vermittelter, überschießender
autonomer Reflexe. Die von der International Association for the Study of Pain
(1979) veröffentlichte Arbeitsdefinition lautet: „Schmerz ist eine unangenehme
sensorische und emotionale Erfahrung, die im Zusammenhang steht mit
tatsächlicher oder potentieller Schädigung oder in Form einer solchen Schädigung
beschrieben wird“. Schmerzen haben nicht nur einen signifikant nachteiligen Einfluss
auf das Wohlbefinden von Tieren, sondern auch auf deren physiologischen Zustand,
was die Wundheilung deutlich verzögert (Otto und Short, 1998). Es ist bekannt, dass
bei unter Schmerz stehenden Patienten eine erhöhte Infektionsrate besteht
(Benedetti, 1990), die wahrscheinlich auf die hinlänglich bekannte immunsuppressive
Wirkung von Kortikosteroiden zurückzuführen ist. Allerdings existieren jedoch auch
Beobachtungen, dass Schmerz (Fujiwara and Orita, 1987) und Stress (Jessop et al.,
1987) das Immunsystem stimulieren können. Ferner ist bekannt, dass die
Schmerzunterdrückung nicht nur im Moment der Einwirkung des Traumas einen
positiven Effekt ausübt, sondern auch die Dauer und Qualität der Rekonvaleszenz
2

Einleitung
günstig beeinflusst. Dies wird damit begründet, dass periphere Noxen zu einer
nachhaltigen Hypersensitivität im Zentralnervensystem führen können. Animal
Welfare und Ökonomie stehen somit nicht in einem Konflikt, da sich eine Investition
in adäquate Schmerzausschaltung durch schnellere Rekonvaleszenz auszahlt. So
konnten Pang et al. (2006), Ting et al. (2003) Fisher et al. (1996), sowie Earley and
Crowe (2002) zeigen, dass die Produktionsleistung der Tiere durch eine
angemessene Schmerzbehandlung vor, während und nach schmerzhaften Eingriffen
signifikant gesteigert war.
Das Ziel der Schmerzbekämpfung impliziert nicht notwendigerweise die Eliminierung
aller Schmerzen, sondern vielmehr die Reduktion und Ausschaltung des
pathologischen Schmerzes, der mit einer Verletzung oder einem Eingriff verbunden
ist. Die Schmerzausschaltung kann dabei entweder durch eine lokale Betäubung,
eine Allgemeinnarkose, oder einer Kombination Beider herbeigeführt werden. In den
letzten Jahren ist in dieser Hinsicht die multimodale Schmerztherapie bei Tieren in
den Fokus gerückt. In Studien aus der Humanmedizin zeigte sich durch die
Kombination verschiedener analgetisch wirkender Substanzklassen, die auf
unterschiedlichen Ebenen der Schmerzwahrnehmung und Schmerzleitung ansetzen,
ein synergistischer Effekt, wodurch die jeweiligen Einzeldosen und die damit
verbundenen unerwünschten Nebenwirkungen verringert werden (Kehlet, 1997,
Kehlet and Wilmore, 2002). Während zum multimodalen Schmerzmanagement beim
Kleintier sowie beim Pferd umfangreiche, wissenschaftlich fundierte Erkenntnisse
bestehen, existieren für das Nutztier, insbesondere für das Rind, hierzu kaum auf
einschlägigen Studien basierende Erfahrungen.
3

Einleitung
Naturgemäß können Tiere, anders als der Mensch, erlebte Schmerzen nicht verbal
kommunizieren. Da das nozizeptive System der Tiere dem des Menschen jedoch
sehr ähnlich ist, sind Analogieschlüsse durchaus legitim (Dawkins, 1982, Endenburg
et al., 2001, Otto, 2008). Rückschlüsse auf die Präsenz und die Intensität des
wahrgenommenen Schmerzes bei Tieren erfolgen dabei einerseits indirekt durch
Verhaltensbeobachtung, aber auch durch direkte, mess- und quantifizierbare
Parameter der kardio-respiratorischen- und die metabolisch-hormonellen
Stressresponse sowie der Akuten-Phase-Antwort.
Bei der Interpretation subjektiver Parameter erfolgt die Einschätzung von Schmerz
durch einen Beobachter, welcher Verhaltensmuster, Haltung und andere Hinweise
(z.B. Vokalisation, Zähneknirschen) dem tierindividuellen schmerzspezifischen
Verhalten zuordnet. Das Ausmaß an Schmerz wird dann beispielsweise auf einer
Linie mit den Endpunkten „kein Schmerz“ und „schlimmstes möglichstes
Schmerzerlebnis“ eingetragen (visual analog scale, VAS (Hudson et al., 2008, Firth
and Haldane, 1999)) oder einem vorher festgelegten numerischen Wert zugeordnet
(numeric rating scale, NRS (Reid and Nolan, 1991)). Da die Wiederholbarkeit und
Verlässlichkeit dieser Werte jedoch stark von der Erfahrung im Beobachten sowie
der persönlichen Schmerzerfahrung des Beobachters abhängen (Valverde et al.,
2005), stellt die Verhaltensbeobachtung eine subjektive und mäßig genaue
Annäherung dar, welche zudem keine Vergleichbarkeit von Werten zwischen Studien
ermöglicht (Anil et al., 2002, Gaynor and Muir, 2002). Dennoch ist diese Form der
4

Einleitung
Schmerzbeurteilung bei Tieren nach wie vor unverzichtbar, da sie zwar nicht sehr
genau aber sehr sensitiv ist (Mathews, 2000).
Um objektive Schmerzparameter zu erfassen, bedient man sich einzelner Elemente
der Stressantwort, die im Wesentlichen aus drei Komponenten besteht: der
endokrinen, der metabolischen sowie die kardio-respiratorischen Stressantwort. Die
endokrine Stressantwort basiert auf einer Aktivitätssteigerung des hypothalamohypophysär-adrenergen
Systems (HPA), des sympathisch autonomen
Nervensystems und der Akute-Phase-Reaktion. Dies bietet diverse mess- und
quantifizierbare Parameter wie Atem- und Herzfrequenz (Morton and Griffiths, 1985,
Weary et al., 2007), Blutdruck, Glucose- (Henke et al., 2008), Laktat- (Henke and
Erhard 2001) und freie Fettsäurespiegel (Greco, 2007), Akute Phase Proteine
(Earley and Crowe, 2002, Doherty et al., 2007, Murata et al., 2004), Substanz P
(Coetzee et al., 2008), ACTH, Katecholamin- (Epinephrin und Norepinephrin) und
Cortisolkonzentrationen im Blut (Mormede et al., 2007, Mellor et al., 2002, Herskin et
al., 2004).
Vor dem Hintergrund, einfache, günstige und praxistaugliche Anästhesieverfahren im
Rahmen der gültigen Arzneimittelgesetzgebung zu entwickeln, wurden in dieser
Arbeit drei Anästhesieprotokolle am Modell der Nabeloperation des Kalbes
miteinander verglichen. Dabei wurde anhand einer Reihe von objektiven und
subjektiven Parametern untersucht, welchen Einfluss diese drei Techniken auf das
neuroendokrine und hämodynamische Gleichgewicht der Tiere ausüben. Die
Inhalationsnarkose wird als „Goldstandard“ der Anästhesiemethoden bei Kälbern für
5

Einleitung
abdominalchirurgische Eingriffe angesehen, jedoch limitiert der damit verbundene
finanzielle und technische Aufwand deren Anwendung außerhalb klinischer
Einrichtungen. Die derzeit am häufigsten verwendete Narkoseform der praktischen
Tierärzte in Deutschland ist eine Injektionsnarkose mit Xylazin und Ketamin. Mit
dieser Narkoseform sind jedoch erhebliche Nebenwirkungen auf das Herz-Kreislauf-
System verbundenen und laut Rings and Muir (1982) ist es fraglich, ob diese
Methode eine ausreichende Schmerzausschaltung für Nabeloperationen erzielt. Eine
Epiduralanästhesie mit dem Lokalanästhetikum Procain in Kombination mit dem
Alpha-2-Agonisten Xylazin in einem großen Volumen (0.5 - 0.6 ml kg -1 ) wurde von
Meyer et al. (2007) als effektive, sichere und kostengünstige Alternative für
Nabeloperationen beim Kalb propagiert. Dabei führt die verzögerte Resorption des
epidural applizierten Xylazins zu einer abgeschwächten kardiovaskulären
Beeinträchtigung (Mpanduji et al., 1999, Meyer et al., 2009). Die drei genannten
Verfahren zur Schmerzauschaltung wurden im Zuge eines multimodalen
Schmerzmanagements mit der parenteralen Applikation von nichtsteroidalen
Antiphlogistika sowie einer Lokalanästhesie im Bereich des Nabels kombiniert.
In einem Großteil der bekannten Studien über anästhetische und antinozizeptive
Effekte verschiedener Medikamente und deren Kombinationen bei Rindern wurde ein
kontrollierter Schmerzreiz durch elektrische Strömungen oder Nadelstiche gesetzt
(Skarda et al., 1990, Junhold and Schneider, 2002, Prado et al., 1999). Obwohl diese
Methoden gute Annäherungen darstellen, um antinozizeptive Effekte zu studieren,
sind sie dennoch nicht mit einem chirurgischen Trauma gleichzusetzen, da die
endokrine Stressantwort durch die Freisetzung vasoaktiver Substanzen durch den
6

Einleitung
Gewebsschaden potenziert wird (Traynor and Hall, 1981, Madsen et al., 1976,
Goldkuhl et al., 2010). Die Untersuchung zum Vergleich der drei Methoden zur
Schmerzausschaltung erfolgte daher am Modell der praxis-üblichen und –relevanten
Nabeloperation.
Um während der Operation einen zuverlässigen Zugang zum arteriellen
Gefäßsystem zu schaffen, regelmäßig Blutproben für arterielle Blutgasanalysen zu
nehmen und kontinuierlich Blutdruck zu messen, wurde bereits ein Tag vor der
Operation ein Katheter in die Aorta abdominalis gelegt. Diverse
Zugangsmöglichkeiten zur permanenten Implantation von arteriellen Kathetern bei
Rindern wurden beschrieben (Gustin et al., 1988, Kotwica et al., 1990, Parker and
Fitzpatrick, 2006), jedoch ist die Aorta gerade bei Kälbern aufgrund des
annehmbaren Durchmessers und der hohen Blutflussgeschwindigkeit besonders
geeignet. Im Gegensatz dazu sind Messwerte der zu diesem Zwecke ebenfalls
häufig verwendeten A. auricularis durch Bewegungen des Ohres oder des gesamten
Kopfes störanfälliger. Bislang erfolgten Aortenpunktionen „blind“, d.h. ohne Kontrolle
durch bildgebende Untersuchungsverfahren (Junhold and Schneider, 2002, Weber et
al., 1992). Die hiermit verbundenen vorstellbaren Komplikationen, wie z.B. einer
Verletzung der Aorta oder benachbarter Organe, führt zu erheblichen Unsicherheiten
des Untersuchers in der Durchführung (Adams et al., 1991, Nagy et al., 2002). Es
wurde daher eine Methode der ultraschall-kontrollierten Punktion der Aorta
abdominalis bei Kälbern entwickelt.
7

Einleitung
Im Rahmen von Studien zum Schmerzmanagement bei Kälbern wurde in den
vergangenen fünf Jahren bei insgesamt 102 Kälbern ein arterieller Zugang in die
Aorta abdominalis gelegt. Bei einem dieser Kälber führte eine punktiosbedingte
Embolisation spinaler Gefäße zu einer ischämischen Myelopathie des
Rückenmarkes im Lendenbereich, welche sich klinisch in einer Paraplegie äußerte.
Diese Komplikation ist ausführlich in Form eines Fallberichts dokumentiert.
In dieser Studie wurde der intraoperative Effekt der drei Anästhesieprotokolle an 30
Kälbern untersucht. Die Langzeitauswirkungen der Anästhesieformen auf die
Rekonvaleszenz, insbesondere die Lungengesundheit, sowie die postoperative
Produktivität dieser Kälber wurden von Fischer et al. 2010 (Manuskript in
Vorbereitung) untersucht und zusammengefasst.
Diese Arbeit gliedert sich somit in drei Abschnitte:
1. Darstellung der ultraschall-geführten Aortenpunktion bei Kälbern,
2. Vergleich der Auswirkungen von Inhalations-, Injektions- und hoher caudaler
Epiduralanästhesie auf die kardiorespiratorischen, metabolischen sowie
hormonellen Stressreaktionen bei Kälbern während einer Nabeloperation,
sowie
3. Fallbericht zum spinalen Infarkt als Komplikation der Aortenpunktion bei einem
Kalb.
8

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MEYER, H., STARKE, A., KEHLER, W. & REHAGE, J. (2007) High caudal epidural
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PANG, W. Y., EARLEY, B., SWEENEY, T. & CROWE, M. A. (2006) Effect of
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PRADO, M. E., STREETER, R. N., MANDSAGER, R. E., SHAWLEY, R. V. &
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RINGS, D. M. & MUIR, W. W. (1982) Cardiopulmonary effects of intramuscular
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function, feed intake, growth, and behavior. J Anim Sci, 81, 1253-64.
TRAYNOR, C. & HALL, G. M. (1981) Endocrine and metabolic changes during
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14

Publikation 1
Publikation 1:
Percutaneous, ultrasonographically guided technique of catheterization of the
abdominal aorta in calves for serial blood sampling and continuous arterial
blood pressure measurement
J. Offinger, J.Fischer, J. Rehage, H. Meyer*
Res. Vet. Sci. (2010), doi:10.1016/j.rvsc.2010.07.016
Clinic for Cattle, University of Veterinary Medicine Hannover, Foundation,
Bischofsholer Damm 15, D-30173 Hannover, Germany
*Corresponding author. Tel.:+49 511 8567302, fax: +49 511 8567693
E-mail address: henning.meyer@tiho-hannover.de (Henning Meyer)
15

Publikation 1
Abstract
The study describes a technique of ultrasonographically guided transcutaneous
catheter implantation into the abdominal aorta of 29 six- to eight-week-old German
Holstein calves. Catheters were implanted between the left transverse processes of
L3 and L4, left in place for two days and used for serial blood sampling and
continuous measurement of blood pressure. Complete cell counts and clinical
examination were performed before, as well as one and five days after implantation.
Catheterization was successful in all calves. The catheter was patent for blood
sampling and pressure recordings at all times. A significant decrease in red blood
cells was found in all animals after catheterization, which remained reduced for five
days. Clinical signs of anaemia were absent. In conclusion, ultrasonographically
guided catheterization of the abdominal aorta provides a continuous arterial access
in calves, whereby the minimal invasive technique and the ultrasonographical
guidance reduces accidental tissue trauma and pain for the animal.
Keywords: arteriopuncture, aortic catheter, arterial blood pressure, ultrasoundguided,
cattle
16

Publikation 2
Publikation 2:
Comparison of isoflurane inhalation anaesthesia, injection anaesthesia and
high volume caudal epidural anaesthesia in calves; metabolic, endocrine and
cardiopulmonary effects
Jennifer Offinger* ,+ DVM, Henning Meyer * ,+ Dr med vet, Jessica Fischer* DVM,
Sabine B.R. Kästner†, Prof Dr med vet, Diplomate ECVAA, Marion Piechotta* Dr
med vet, Jürgen Rehage*, Prof Dr med vet, Diplomate ECBHM
*Clinic for Cattle, University of Veterinary Medicine Hannover, Hannover, Germany
†Small Animal Clinic, University of Veterinary Medicine Hannover, Hannover,
Germany
+ both authors contributed equally to this paper
Correspondence: Jennifer Offinger, Clinic for cattle, University of Veterinary Medicine
Hannover, Bischofsholer Damm 15, 30173 Hannover, Germany
E-mail: jennifer.offinger@tiho-hannover.de
Tel.:+49 511 856
Fax: +49 511 856 7693
17

Publikation 2
Abstract
Objective To compare three different anaesthetic protocols for umbilical surgery in
calves regarding the quality of analgesia and cardiopulmonary side effects
Study Design Prospective, randomised experimental study
Animals Thirty healthy German Holstein calves.
Methods All calves underwent a standardised umbilical surgery. The inhalationgroup
(INH) received isoflurane in oxygen after induction of anaesthesia with 0.1
mg kg -1 xylazine IM and 2.0 mg kg -1 ketamine IV, the injection-group (INJ) was treated
with 0.2 mg kg -1 xylazine IM and 5.0 mg kg -1 ketamine IV injection, redosed every 10-
15 min with half the initial dose of ketamine, while the epidural-group (EPI)
underwent a high volume caudal epidural anaesthesia of 0.2 mg kg -1 xylazine diluted
to a final volume of 0.6 ml kg -1 with procaine 2%. All calves received a periumbilical
infiltration of procaine and pre-emptive IV application of flunixine (2.2 mg kg -1 ). The
endocrine stress response was determined through analysis of norepinephrine (NE)
and cortisol concentrations at preset intervals up to five hours after surgery. A visual
analogue scale (VAS) was applied to monitor intraoperative nociception. At the same
time, cardiopulmonary variables and arterial blood gases were measured.
Results The highest VAS-scores were recorded for Group INJ, followed by Group
EPI and Group INH. Cortisol and NE-concentrations were significantly lower in Group
EPI compared to Group INH and Group INJ. Partial pressure of oxygen (PaO 2 ) in
Group INJ was significantly decreased during surgery. Calves of Group INH and INJ
developed decreased levels of arterial pH and high levels of partial pressure of
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Publikation 2
carbon dioxide (signs of respiratory acidosis), mean arterial blood pressure and
systemic vascular resistance.
Conclusion High volume caudal epidural anaesthesia provided a more continuous
antinociception than injection anaesthesia while inducing less cardiopulmonary side
effects.
Clinical relevance For umbilical surgery, high volume caudal epidural anaesthesia
provides a practical, inexpensive and safe anaesthetic protocol for calves undergoing
umbilical surgery.
Key words: epidural anaesthesia, pain management, calf
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Publikation 2
Introduction
Abdominal surgery in calves is commonly performed under inhalation anaesthesia
(halothane (Steffey & Howland 1979; Trent & Smith 1984; Staller et al. 1995) or
isoflurane (Kerr et al. 2007)) or using intravenous (IV) or intramuscular (IM) injection
of xylazine and ketamine (Waterman 1981; Rings & Muir 1982; Greene & Thurmon
1988). Even though the benefits of inhalative agents are unambiguous, the
requirement of special equipment renders them unsuitable for field-use. Injection
anaesthesia is most frequently employed in farm animal practice, but is associated
with considerable cardiopulmonary side effects (Campbell et al. 1979; Picavet et al.
2004) while not even providing adequate analgesia for umbilical surgery in all cases
(Rings & Muir 1982).
As an alternative to general anaesthesia, high volume caudal epidural anaesthesia
using a combination of spinal local anaesthetics and α 2 -adrenergic agonists has been
utilised in cattle practice in recent years. Epidural application of 0.1 mg kg -1 xylazine
diluted to a final volume of 0.5 - 0.6 ml kg -1 with procaine (2%) proved to be effective,
safe and economic for umbilical surgery in calves (Meyer et al. 2007), while the
delayed manner of systemic resorption of epidural xylazine induced only mild
cardiopulmonary depressant effects in ruminants (Mpanduji et al. 1999; Meyer et al.
2009). While numerous experimental studies have examined the anaesthetic and
antinociceptive effects of different drug combinations in cattle, few have investigated
reactions to actual surgical trauma. Electrical stimulation or pinprick (Skarda et al.
1990; Prado et al. 1999; Junhold & Schneider 2002) are regarded as good
20

Publikation 2
estimations to determine antinociceptive effects, but do not accurately reflect surgical
manipulation, as the endocrine response with release of vasoactive substances
occurs in proportion to the operative trauma (Traynor & Hall 1981; Goldkuhl et al.
2010).
The aim of this study was to compare analgesic quality and cardiopulmonary impact
of three anaesthetical regimes (inhalation anaesthesia, injection anaesthesia and
high volume caudal epidural anaesthesia) for umbilical surgery in calves. To simulate
authentic conditions, a multimodal approach to pain management was chosen
(anaesthesia plus local infiltration of the umbilical area as well as pre-emptive NSAID
application) and calves underwent an actual surgical intervention.
Materials and methods
Animals
Thirty healthy German Holstein calves (7 female, 23 male) with an average age
(mean ± SD) of 45.9 ± 6.4 (range 36 - 59) days and body weight (BW) of 66.1 ± 6.2
(range 57.0 – 83.5) kg were included in this study. The study was conducted under
the guidelines and ethical review of the Research Animal Act of the Lower Saxony
Federal State Office for Consumer Protection and Food Safety (research permit
number 33.9-42502-04-08/1572).
Calves were housed in individual pens on straw bedding, were fed milk (10 % of
BW per day) divided into four feedings and had free access to hay, calf starter and
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Publikation 2
water. Daily clinical examination commencing two weeks prior to the start of the study
ensured calves were acclimatised to handling.
Study design and drug application
All 30 calves were randomly assigned to one of three anesthetic protocols:
Inhalation- (INH), injection- (INJ) and epidural- (EPI) anaesthesia, before undergoing
a standardised surgical procedure (Baird 2008), whereby the umbilical stalk was
removed. Food was withheld for 12 hours prior to induction of anaesthesia to prevent
intraoperative regurgitation and excessive bloating.
Calves of the Group INH were initially sedated by intramuscular (IM) injection of
0.1 mg kg -1 2% xylazine (Rompun, Bayer Vital GmbH, Leverkusen, Germany),
followed by slow intravenous (IV) administration of 2.0 mg kg -1 ketamine (Ketamin
10%, Selectavet GmbH, Weyarn-Holzolling, Germany) (Tadmor et al. 1979).
Following endotracheal intubation (Tubus, blue line, ID 8.5, Smith Portex Critical
Care GmbH, Grasbrun, Germany) anaesthesia was maintained with isoflurane to
effect with vaporizer settings between 1.5 and 2 Vol.-% (CuraMED Pharma GmbH,
Karlsruhe, Germany) and an oxygen flow rate of 1-2 L min -1 using a circle breathing
system operated in a semi-closed mode (Sulla 808, Dräger, Lübeck, Germany).
Group INJ was treated with IM injection of xylazine at a dose of 0.2 mg kg -1 . After ten
minutes, 5.0 mg kg -1
ketamine IV was slowly injected (Waterman 1981; Carroll &
Hartsfield 1996). Anaesthesia was maintained with intermittent redoses of 2.5 mg kg -
1 ketamine IV at preset 15 min intervals. However, if the depth of anaesthesia
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Publikation 2
deemed insufficient as assessed by positive nociceptive responses (purposeful
movements of the head, neck, trunk or limb), ketamine re-doses were applied ahead
of schedule. If the duration of the operation exceeded 60 minutes, a follow up dose of
xylazine (0.1 mg kg -1 ) was applied by the IM route. In replicating field conditions, the
animals of Group INJ were not orotracheally intubated and were breathing room air
during surgery.
Calves of Group EPI received a caudal epidural injection of 2% xylazine at a dose of
0.2 mg kg -1 , diluted with 2% procaine solution (Procasel 2%, Selectavet GmbH,
Weyarn-Holzolling, Germany) to a final volume of 0.6 mL kg -1 (equivalent to 12
mg / kg Procaine; modified from Meyer et al. (2007)). The sacrococcygeal area was
surgically prepared and an 18 gauge hypodermic needle (length 40 mm, Braun
Melsungen AG, Melsungen, Germany) was aseptically introduced into the
lumbosacral epidural space. Correct needle placement was confirmed by the hanging
drop technique (Skarda 1986) and loss of resistance to injection. Epidural injection
was performed with a rate of approximately 0.5 mL s -1 with the fluid prewarmed to
body temperature. After epidural injection calves were maintained in sternal
recumbancy for an additional two minutes to facilitate an equal distribution of
anaesthetic within the epidural space.
In addition to all anaesthetic protocols, local anaesthesia of the umbilical region by
rhomboid infiltration with 0.5 ml kg -1
2% procaine was carried out in all animals.
Furthermore, all calves received 2.2 mg kg -1 Flunixine IV (Finadyne RPS, Intervet
GmbH, Germany) 30 minutes prior to surgery. An infusion of warmed 0.9% saline
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Publikation 2
solution (37°C) at a rate of 0.2 ml kg -1 min -1
and two electrical heating pads
(43 × 38 cm, 37°C, Eickemeyer, Tuttlingen, Germany) were used to reduce
intraoperative hypothermia. All surgeries were carried out at a room temperature of
20-22°C.
Baseline measurements were obtained in the standing calves in the operating theatre
(- 60 min). After administration of the drugs, calves were positioned in dorsal
recumbency. To prevent uncontrolled cranial migration of epidural drugs, the animals
were placed on a table that was cranially elevated (at an angle of 3-5°), so that the
shoulder became the highest point of the spinal column. Furthermore, the muzzle of
the calf was positioned below the pharyngeal area for drainage of fluids such as
saliva or regurgitated ruminal fluid, thus reducing the risk of their aspiration. When
the calf was restrained in dorsal recumbancy, pre-surgical parameters were recorded
(-30 min). Thereafter, intra-operative measurements were taken at incision (0 min)
and 15, 30, 45 min into the operation and at the end of the surgical procedure (65
min). On completion of the surgery, calves were positioned in sternal recumbency
and kept in a calm environment on soft bedding. Calves were no longer restrained,
thus were free to stand up or resume sternal recumbency during this period. Further
measurements were taken 95, 125, 185 and 365 min after commencing the
operation. The calves were then returned to their stalls and visually monitored until
they regained the righting reflex and were able to stand. During recovery, hind limbs
of calves in Group EPI were hobbled to avoid musculoskeletal injuries.
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Publikation 2
Instrumentation
One day before the operation, a catheter introducer set (8F Walter Veterinär
Instrumente e.K., Germany) was aseptically placed into the left jugular vein using the
Seldinger technique (Seldinger, 1953). An arterial catheter (Cavafix Certo Mono, OD
1.4 mm, ID 0.8 mm, B.Braun Melsungen AG, Melsungen, Germany) was placed
transcutaneously into the abdominal aorta as described in detail elsewhere (Offinger
et al. 2010). The catheters were implanted under local anaesthesia and remained in
place for two days. Calves received 2.5 mg kg -1 10% enrofloxacine (Baytril, Bayer
Vital GmbH, Leverkusen, Germany) for five consecutive days. On the day of the
operation, a 110 cm 7 F Swan-Ganz thermodilution catheter with an in-line
temperature sensor (Citri Cath TD Catheter, Becton, Dickinson Critical Care
Systems, Heidelberg, Germany) was introduced aseptically into the jugular vein and
connected to a fluid-filled transducer (Smith pvb Critical Care GmbH, Grasbrun,
Germany). The level of the scapulohumeral joint was used as the reference zero
level in the standing calf and the centre of the thorax was considered as the
reference zero level in dorsal and sternal recumbency for calibrating the transducer
(Amory et al. 1992; Lewis et al. 1999). The thermodilution catheter was advanced
until the tip of the catheter reached the wedge position in the pulmonary artery.
Characteristic pressure waveforms were used to confirm correct catheter positioning.
The aortic catheter was also connected to a calibrated transducer via a fluid-filled
extension set for continuous measurement of arterial blood pressure. All catheters
were flushed after each sampling with heparinised 0.9% sterile saline solution
(10,000 IU heparin x L -1 , Heparin-Calcium, Ratiopharm, Ulm, Germany) to ensure
patency.
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Publikation 2
Measured parameters
Analgesia and endocrine stress response
The quality of anaesthesia and analgesia was assessed by observing the calves’
reactions to the following pre-set intra-operative procedures on a visual analogue
scale (VAS) (Anil et al. 2002): Incision of the skin, incision of muscular tissue,
opening of abdominal cavity, exploration of abdominal cavity, umbilical resection,
suture of peritoneum, sutures of muscular tissue and sutures of skin. Responses to
each event were subjectively interpreted and individually recorded on a line ranging
from 0 (no pain) to 100 mm (very severe pain).
Cardiopulmonary parameters
Blood pressures were measured and recorded with a cardiovascular monitor
(IntelliVue MP50, Phillips Medizin Systeme, Hamburg, Germany). Central venous
blood pressures (CVP), pulmonary arterial pressures (Carrick et al. 1989) and central
blood temperature were measured via the different ports of the Swan-Ganz catheter,
and heart rate (HR), as well as systemic arterial blood pressure (MAP), via the aortic
catheter. Cardiac output (CO) was determined using the thermodilution technique
(Sprung et al. 1984) by injecting 5 mL of cold (0–5°C) 5% dextrose solution through
the proximal port of the catheter and recording the change in pulmonary artery
temperature as previously described by Meyer et al. (2009). Respiratory rate (RR)
was measured by visual observations of thoracic excursions over a period of 1 min.
Blood samples for blood-gas analysis were drawn anaerobically from the distal lumen
of the Swan-Ganz- and the aortic catheter for mixed venous ( v¯ ) and arterial ( a ) blood
26

Publikation 2
gases, respectively. The samples were placed on ice and analysed within 10 min of
collection. Blood gas analysis included measurement of blood pH, partial pressure of
oxygen (pO 2 ) and carbon dioxide (pCO 2 ), base excess (BE) as well as oxygen
saturation (S a O 2 ) using an automated blood gas analyser (Rapidlab 348, Bayer
Diagnostics) after prior adjustment for blood temperature and haemoglobin
concentration (Celltax MEK-6108G, Nihon-Kohdan, Rosbach, Germany).
Calculations
Cardiopulmonary parameters were calculated using the following standard equations:
• stroke volume (SV) [mL beat -1 ]: SV= (CO/HR) × 1000 (Amory et al. 1992)
• systemic vascular resistance (SVR) [dynes×s×cm -5 ]: SVR= ((MAP –
CVP)/CO) × 79.9
• pulmonary vascular resistance (PVR) [dynes×s×cm -5 ]: PVR = ((MPAP –
PCWP)/CO) × 79.9 (Amory et al. 1992)
• tidal volume (V T ) [L]: V T = Minute Ventilation (V E )/ RR, whereby V E was
determined by the minute volumeter.
• arterial and venous oxygen content were calculated according to (Wilson et al.
1988) and (Sprung et al. 1983):
o arterial oxygen content (C a O 2 ) [mL dL -1 ]: C a O 2 = [Hb] × S a O 2 × 1.36 + (p a O 2
× 0.003),
o mixed venous oxygen content (C v¯ O 2 ) [mL dL -1 ]: (C v¯ O 2 )= [Hb] × S v¯ O 2 ×
1.36 + (p v¯ O 2 × 0.003)
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Publikation 2
• alveolar oxygen tension (pAO 2 ) was calculated according to (Uystepruyst et al.
2002):
pAO 2 [mmHg] =: (BP - 47) × FIO 2 – (p a CO 2 /RQ), where BP is the barometric
pressure (in mmHg) on the day of the surgery, RQ is the respiratory quotient
determined as 0.80 by (Vermorel et al. 1989) and FIO 2 is the fraction of
inspired oxygen (0.2095 on room air).
• oxygen content in pulmonary capillary blood (CcO 2 ) [mL dL -1 ]: CcO 2 = [Hb] × 1* ×
1,36 + (pAO 2 × 0,003)
(*As the oxygen saturation in capillary blood is assumed to be 100%, the Hb is
multiplied by the factor 1)
• Pulmonary shunt (Qs/Qt) [%]: Qs/Qt = ((CcO 2 - C a O 2 ) / (CcO 2 - C v¯ O 2 )) x 100
Venous blood samples for determination of serum cortisol (Cortisol-Immulite 1000-
Test ® , Siemens Healthcare Diagnostics GmbH, Eschborn, Germany), plasma
epinephrine and norepinephrine (2 CAT RIA, Labor Diagnostika Nord GmbH & Co.
KG, Nordhorn, Germany) from each calf were collected from the jugular vein (via the
catheter) into serum tubes and EDTA-coated tubes, respectively. For cortisol, the
intra-assay coefficient of variation (CV %) was 6.3-10.0% and the inter-assay CV %
was 5.8-8.8%. For both, epinephrine and norepinephrine, intra-assay coefficients of
variation were 4.6% and the inter-assay CV % were 6.1%. Samples were obtained
synchronous to all other measurements and stored at -80°C before analysis.
Data are presented as mean ± standard deviation (SD). A value of P < 0.05 was
considered significant. Normal distribution of data was tested by determining the
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Publikation 2
Shapiro-Wilk W and associated P value as well as by screening the normal
probability plots. Values were log transformed whenever necessary to achieve a
normal distribution. A two-way analysis of variance for repeated measurements
(factor group, time and time × group; PROC GLM, Repeated-Statement) was used to
determine the main effects of groups and time as well as the interaction between
group and time. Consecutive tests were used for multiple comparisons of means
whenever the F-test was significant. Within groups paired t-tests were used to
compare means of different time points with baseline (PROC PRT) and a modified t-
test (PROC LSMEANS; TDIFF/PDIFF option) was used to compare means between
treatment groups at different time points. The statistical analysis was conducted
using a statistical software package (SAS 9.1 SAS Institute Inc., Cary, N.C., USA).
Results
All three anaesthetic regimes provided sufficient anaesthesia for umbilical surgery to
be carried out. The resection of umbilical tissue was uncomplicated in all calves and
the mean duration of surgery was 65 min (range 56 – 73 min).
Analgesia and behavioural changes
Maintenance of anaesthesia was uneventful in Group INH. In five of ten calves from
Group EPI intra-operative focal muscle twitching or spontaneous foreleg movement
occurred. However, none of these events occurred simultaneously with the predefined
actions of surgical manipulation. In six out of ten calves in Group INJ,
ketamine had to be redosed ahead of the predetermined interval responses to pre-
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Publikation 2
set intraoperative procedures indicated an insufficient depth of anaesthesia. Despite
slow IV injection of ketamine, on four occasions the intraoperative administration led
to respiratory arrest for up to two minutes. In these cases intermittent manual
compression of the animals’ thorax was carried out until spontaneous breathing
resumed. At all time points, calves in Group INJ had higher VAS scores compared to
Group EPI. The lowest scores occurred in Group INH (Fig. 1). Recoveries were
smooth and rapid. All animals were able to stand up without assistance within two
hours of completion of the surgery.
Figure 1 near here
Measurements of endocrine and metabolic stress response
Cortisol
During the course of the operation, cortisol concentrations increased successively
until 15 min into the operation, plateaued until the end of the surgery and decreased
from then on, resuming baseline levels 60 min after surgery (Table 1). Mean cortisol
concentrations throughout the surgical period were significantly lower in Group EPI
compared to Group INH but only significantly reduced at 45 min into surgery
compared to INJ.
Catecholamines
A surge in epinephrine from baseline values of < 10 ng mL -1 to values over 200 ng
mL -1 in Group INH and Group INJ and to values of 140 ng mL -1 in Group EPI were
observed directly after surgical incision (Table 1). Epinephrine levels steadily
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Publikation 2
decreased during surgery, but remained elevated compared to baseline until the end
of the observation period. At the beginning and the end of the surgical period (0 min
and 65 min) mean norepinephrine concentrations of Group INH were significantly
elevated compared to groups INJ and EPI (Table 1).
Table 1 near here
Effects on the cardiopulmonary system
In all calves, the administration of anaesthetics and subsequent positioning into
dorsal recumbency caused an initial significant decrease of HR, SV, CO, MAP, CVP
and BE, whereas SVR, PVR and RR significantly increased in all groups (Tables 2-3;
Fig. 2).
Figure 2 near here
-
The surgical procedure itself led to transient decreases in CVP, BE and HCO 3
(Tables 2-3). For these parameters, no significant differences were detected among
the groups and all parameters returned to baseline after surgery. HR and SV were
initially elevated by the operational stimulus before HR successively decreased and
SV successively increased in course of the surgery. In Group INH p a O 2 was
significantly higher whereas body temperature, PAP and PVR were significantly
lower than in groups INJ and EPI (Tables 2-3). Injection anaesthesia led to a
significant decrease in p a O 2 and SaO 2 , and significantly increased values of PAP and
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Qs/Qt (Fig. 3) in comparison to groups INH and EPI. Tidal volume (V T ) of Group INH
gradually increased in the course of the surgery from 0.27 to 0.33 L (data not shown).
Table 2 and Figure 3 near here
Mean body temperatures in all groups decreased over the course of anaesthesia,
whereby the temperature drop of calves of the Group INH was significantly greater
compared to groups INJ and EPI. This difference was sustained until 60 minutes
after the operation (Table 2).
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Discussion
All three anaesthetic regimes investigated in this study were suitable for umbilical
surgery in calves. However, according to VAS assessment, most nociceptive
responses to all stages of surgical intervention occurred during ketamine based
injection anaesthesia. Ketamine, as dissociative anaesthetic agent, is known to
induce good somatic, yet poor visceral analgesia (Carroll & Hartsfield 1996). The
overt responses to exploration of the abdominal cavity in the calves might be a
reflection of this, even though it was used in combination with xylazine. Monitoring of
anaesthetic depth in ketamine based injection anaesthesia is difficult because
protective reflexes are maintained and often the occurrence of purposeful
movements is the only parameter indicating inadequate depth of anaesthesia. In the
current study, ketamine re-doses were often necessary ahead of schedule and it was
difficult to accomplish a constant level of anaesthesia. Respiratory depression after
IV redosing of ketamine, as seen in all calves in this study, have also been described
by other authors (Lin 1996; Carroll & Hartsfield 1996) and may, in the extreme cases
of respiratory arrest, lead to severe problems in the field situation, especially if the
surgeon has no qualified assistance.
Regional anaesthesia like epidural anaesthesia represents a type of local
anaesthesia without any influence on consciousness. Even though epidurally
administered xylazine exerts some systemic effects owing to the absorption of the
drug through the longitudinal epidural veins and possibly the lymphatics (Lee et al.
2001), sedative or hypnotic effects are only mild. Therefore, it is difficult to distinguish
33

Publikation 2
whether movement by the animals in Group EPI represent a reaction to an aversive
sensation caused by surgical intervention or if they are an expression of discomfort
being restrained in an unfamiliar proprioceptive state. In an attempt to prevent
misinterpretation of the VAS, we recorded specific reactions only to pre-defined intraoperative
procedures which are commonly regarded as painful (e.g. the incision of
the skin or sutures of muscular tissue).
As expected the INH anaesthesia was rapidly adjustable and an adequate depth of
anaesthesia was easy to maintain, which is supported by the low VAS. By inference,
intra-operative agitations reflect an unpleasant and aversive sensory experience
(pain) suffered by the calf (Anil et al. 2002). According to the VAS, the EPI
anaesthesia did not alleviate intraoperative pain as much as INH anaesthesia, but
provided superior analgesia compared to the INJ anaesthesia. However, low VAS
scores alone are insufficient to indicate low pain sensation, as immobility in inhalation
anaesthesia is due to depression of spinal alpha-motor neurons and not due to
analgesia alone.
Cortisol levels increased in response to the surgical procedure in all three groups,
indicating that neither inhalation anaesthesia, nor injection anaesthesia or epidural
anaesthesia were able to prevent the surgical stress response. A total suppression of
the endocrine stress response is unachievable, because general anaesthesia has
little effect on the direct release of cytokines into the bloodstream (acute phase
response) after local trauma and injury (Imura et al. 1991; Desborough 2000).
Increased cortisol levels are not a specific indicator for pain, as they are also
34

Publikation 2
associated with stress and fear. In ponies under volatile agent anaesthesia,
abdominal surgery did not induce a greater cortisol and catecholamine response than
anaesthesia alone, indicating that the adrenocortical response to anaesthesia is
already maximal and cannot be further increased by additional stimuli (Taylor et al.
1998). Similar results for cattle (Anderson & Muir 2005) suggest that general
anaesthesia itself is intensely distressful despite the absence of nociceptive
stimulation and tissue trauma from surgery. In man, inhalation anaesthesia was less
effective than neuroleptic, spinal or epidural anaesthesia in reducing the endocrine
response to surgery (Kehlet 1979). This may account for the significantly elevated
norepinephrine levels in Group INH observed immediately after incision and 65 min
into surgery.
The rise in cortisol in Group EPI when the calf was placed in dorsal recumbency
again reflects the reaction of a conscious, mildly sedated animal to unfamiliar
manipulations. However, during surgery, when actual noxious stimuli were applied, a
diminished stress response after spinal epidural anaesthesia similar to dogs (Stanek
et al. 1980) and man (Ecoffey et al. 1985; Stevens et al. 1991; Kehlet 2000)
compared to general anaesthesia could be confirmed by this study. The blunted
surgical stress response after epidural administration of xylazine is due to its local
effect on alpha-2-receptors located in the dorsal horn neurons of the spinal cord.
Activation of these receptors inhibits the release of norepinephrine and substance P,
thus decreasing neuronal activity and, in turn, inhibiting rostral transmission of
nociceptive impulses (Caron & LeBlanc 1989; Prado et al. 1999). Studies in man
found the use of epidural anaesthesia to completely suppress the stress response
35

Publikation 2
resulting from procedures below the umbilicus (Kehlet 1984, Kehlet 1988). A
complete sympathetic and somatic blockade of the surgical site, affecting not only the
nociceptive, but also non-nociceptive pathways, such as the sympathetic innervation
to the adrenal glands however, requires an extensive epidural anaesthesia reaching
from T4 to S5 (Engquist et al. 1977). According to Meyer et al. (2007), a caudal
epidural application of 0.4 ml kg -1 BW (20 ml into a 50 kg calf) of contrast medium in a
calf migrated cranially as far as the T12, hence we assume that applying 0.6 ml kg -1
BW as performed in this study, will still be insufficient to induce the anaesthesia
necessary to induce complete sympathetic and somatic blockage. Thus, the local
release of stress response mediators from the surgical site extending cranially of the
umbilicus and the dose related lack of extent of neuronal blockage may explain the
incomplete effects of the EPI-anaesthesia on the stress response to umbilical
surgery. Application of higher volumes risks blocking the phrenical nerve, originating
in the fifth to seventh cervical segment, and thus causing a motor blockage of the
diaphragm, which would in turn require intubation and diligent monitoring by a
qualified assistant.
The effects of dorsal recumbancy in this study are in accordance with results of
Meyer et al. (2009). The change in positioning leads to compression of the caval vein
by abdominal viscera and, in consequence, reduces venous pre-load in all calves.
This, in addition to xylazines’ bradycardic effect and depression of cardiac
contractility (Campbell et al. 1979; Knight 1980) causes an initial significant reduction
in CO and MAP (Antonaccio et al. 1973). Statistically significant differences among
cardiovascular parameters of the three groups after inducing anaesthesia and before
36

Publikation 2
commencing surgery are only apparent in MAP, whereby the severity of hypotension
in the Group INH is greater compared to the Group INJ and EPI. Isofluranes’
vasodilatative and hypotensive effect is described in foals (Read et al. 2002), dogs
(Mutoh et al. 1997) and mice (Janssen et al. 2004), and accounts for the reduced
MAP and SVR in animals of Group INH.
Due to incomplete afferent somatic and sympathetic neural blockage, surgical stress
caused by abdominal surgery inevitably leads to a release of epinephrine and
norepinephrine immediately after incision, regardless of the anaesthetical protocol
used (Bromage et al. 1971; Traynor & Hall 1981). The positive chronotrope, inotrope
and dromotrope effects of these catecholamines on the heart are reflected in all
groups by an instantaneous increase in CO (as a product of HR and SV). In Group
EPI, HR is not elevated during the operation, yet CO is maintained by a
compensatory increase in SV. Vasoconstrictive effects of epinephrine and
norepinephrine lead to an increased SVR and MAP in Group INJ and INH, but
interestingly, not in Group EPI. Studies by Hogan et al. on rabbits (Hogan et al. 1994)
and Bromage et al. (1971) on man suggest a dilatation of capacitance vessels
evoked by sympathetic blockade following high volume caudal epidural anaesthesia.
This vasodilatation is postulated to result from passive distension of the mesenteric
veins by increased CVP, which was also observed in the Group EPI. To the best of
our knowledge, no such studies have been carried out in ruminants. If the same
mechanism applies in cattle, it would account for the reduced SVR and MAP in
Group EPI, compared to Group INH and INJ.
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Publikation 2
As in this study the RR rate of Group INH increased, but the p a CO 2 remained at a
high level (Fig. 3), we proposed that the central respiratory depressant effect of
isoflurane (Hikasa et al. 1997) may lead to a reduced tidal volume (V T ) or an
increased dead space ventilation, or both. As we did not include pre-anaesthetic
pulmonary function measurements in this study, we had no base value for the
standing unanaesthatised calf for comparison. However, a study on healthy calves of
similar age (Reinhold et al. 2002) determined a V T of 0.64 ± 0.9 L, which is decidedly
above the intra-operative level of Group INH (gradually increasing from 0.27 to
0.33 L), hence we infer that a decrease in V T in Group INH occurred after inducing
anaesthesia and positioning the calves in dorsal recumbancy. It is also known that
the normal stimulation of ventilation caused by increased p a CO 2 is depressed by the
inhalation anaesthetics, presumably due to their direct actions on the medullary and
peripheral chemoreceptors (Hirshman et al. 1977; Knill et al. 1983). The excessive
supply of oxygen may in this case mask an actual ventilation-perfusion mismatch, as
enough oxygen diffuses into the blood, but insufficient CO 2 gets removed from it.
In Group INJ considerable hypoxaemia, reaching mean paO 2 levels of 66.2 mmHg,
was observed. This is well below recommended values of 80 - 110 mmHg
(McDonnell & Kerr 2007). The respiratory depressant effect of xylazine (Rings & Muir
1982) is seen as the cause of the hypoxia, which was further exacerbated by the
respiratory depression following slow IV ketamine redoses. The hypoxaemia and the
significantly increased PVR in Group INJ suggest a definite ventilation-perfusion
mismatch, which is confirmed by the increased pulmonary shunt. It should therefore
be stressed that if no alternative to the combined xylazine and ketamine anaesthesia
38

Publikation 2
can be accomplished, oxygen supplementation is highly recommended during INJ
anaesthesia to provide for adequate oxygenation.
Intra-operatively, calves of Group INH and INJ developed an acute decompensated
respiratory acidosis indicated by acidaemia (Fig. 3) and hypercapnia and almost
unchanged values of BE and HCO - 3 . This is mostly attributed to the respiratory
depressant effects of xylazine, ketamine and isoflurane (Hikasa et al. 1997), but also
due to the change in positioning as described above. In contrast, calves of Group EPI
maintain a stable acid base balance throughout the surgical period. Furthermore, the
influence of the epidural anaesthesia regarding cardiopulmonary parameters was
negligible, emphasizing the limited impact of this anaesthetic protocol on the
cardiovascular system. This is in agreement with the existing opinion that epidurally
applied xylazine unfolds systemic action, yet in a delayed and more moderate
manner than after IV or IM application, therefore creating fewer cardiopulmonary
depression (Junhold & Schneider 2002; Picavet et al. 2004).
Alpha-2-c-receptors mediate hypothermia that accompanies xylazine administration
(Lemke 2007). This anaesthetic drug depression of muscular activity, together with a
reduced metabolism and depression of hypothalamic thermostatic mechanisms,
account for the drop in body temperature in all three groups despite active heating
and infusion of warmed saline solution. Body temperatures of calves in Group INH,
however, remain significantly below those of Group INJ and EPI, from the start of the
surgery until 60 min thereafter. The heat loss in this group is augmented by the
inhalation of cold gases, causing minimal values in individual calves of 36.7°C. This
39

Publikation 2
can definitely be regarded as a disadvantage of INH anaesthesia. In a study on
calves (Olson et al. 1983) found that cold-stressed calves show a linear decrease in
leucocytes and may thus compromise natural host defence capabilities. In man,
hypothermia adversely affects antibody- and cell-mediated immune defences, as well
as the oxygen availability in the peripheral wound tissues. Consequentially,
postoperative hypothermia is known to increase the incidence in surgical wound
infections and is furthermore associated with delayed post-anaesthetic recovery
(Doufas 2003; Polderman 2009).
Increased economic pressures have caused selection against general anaesthesia
and the need for practical, cheap and safe alternatives within the legal framework of
food animal practice is apparent. The inhalation anaesthesia will certainly remain the
gold standard in calf anaesthesia, but from a practical point of view, repeated
ketamine injections are difficult to accomplish when unassisted. However, qualified
assistance definitely becomes a prerequisite when anaesthetic machines are utilised.
Personnel expenditures, acquisition costs and regular maintenance of anaesthetical
machines will, even in the future, limit inhalation anaesthesia subject to use within
large animal clinics. In contrast, high volume caudal epidural anaesthesia requires a
single application and no sophisticated or expensive equipment.
In summary, high volume caudal epidural application of xylazine and procaine in
combination with local rhomboid infiltration of local anaesthetic around the umbilicus
and pre-emptive application of flunixine-meglumine provided a practical, inexpensive
and safe anaesthetic protocol for calves undergoing umbilical surgery, as it has little
40

Publikation 2
effect on cardiopulmonary variables. In comparison to inhalation- and injectionanaesthesia,
intraoperative stress response was reduced and most cardiopulmonary
parameters remained unaltered and within reference ranges. It may therefore be
concluded that for umbilical surgery, high volume caudal epidural anaesthesia can be
promoted as an alternative to inhalation anaesthesia and should definitively be
regarded as superior to injection anaesthesia regarding cardiopulmonary side effects
and analgesic quality.
Aknowledgements
The authors thank Katrin Koslowski for her technical support.
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Figures
b
30 INH
INJ
EPI
b
b
b
VAS
20
ab
b
b
b
c
b
a
10
a
a
a
a
0
Incision of the skin
a
Incision of muscular tissue
Opening of abdominal cavity
Surgical Manipulation
Umbilical resection
Sutures of peritoneum
Intraoperative procedures
Sutures of muscular tissue
a a
Sutures of skin
Figure 1 VAS scores (mean ± SD) of calves undergoing umbilical surgery under
inhalation (INH; n=10), injection (INJ; n=10) and high volume caudal epidural
anaesthesia (EPI; n=10) at pre-determined intraoperative procedures. Different
letters denote significant differences between treatments (p < 0.05).
50

Publikation 2
MAP [mmHg]
180
160
140
120
100
80
a
a
a
ab
a
ab
ab
a
a
ab
a
ab
a
b
INH
INJ
EPI
a
b
60
40
20
0
-60
b
-30
0
b
15
b
b
30
b
45
b
65
b
group effect: p = 0.0326
time effect: p < 0.0001
time x group effect: p < 0.0001
95
b
125
Time relative to start of the operation [min]
2400
2200
a
a
INH
INJ
EPI
SVR [dynes s cm -5 ]
2000
1800
1600
1400
1200
1000
800
a
a
a
a
a
a
a
a
a
b
c
a
b
c
600
400
0
-60
b
-30
0
b
15
b
30
b
45
b
65
group effect: p = 0.0002
time effect: p = 0.0002
time x group effect: p < 0.0001
95
125
Time relative to start of operation [min]
Figure 2 Mean arterial blood pressure (MAP) and systemic vascular resistance (SVR)
of calves undergoing umbilical surgery under inhalation (INH; n=10), injection (INJ;
n=10) and high volume caudal epidural anaesthesia (EPI; n=10). Baseline values (-
60) are determined in the standing calf in the operating theatre. Between -60 and -30
min, calves were anaesthatised and positioned into dorsal recumbency (light grey
underlay). The surgical period is marked by a dark grey underlay. Symbols with a dot
differ significantly from baseline (p < 0.05). For each given point in time, significant
differences between experimental groups are indicated by different letters.
51

Publikation 2
SaO 2
[%]
105
100
95
90
85
80
a
ab
b
a a a a a
a
a
ab
ab
ab
b
ab
a
b
INH
INJ
EPI
p a
CO 2
[mmHg]
80
75
70
65
60
55
50
a
b
a
a
a
b
a
b
a
b
a
ab
INH
INJ
EPI
75
70
0
-60
-30
0
b
b
15
b
30
b
45
65
group effect: p = 0.0118
time effect: p = 0.1120
time x group effect: p = 0.0052
95
125
185
365
45
40
35
0
-60
c
-30
0
b
c
15
c
30
c
45
b
65
group effect: p = 0.0013
time effect: p < 0.0001
time x group effect: p < 0.0001
95
125
185
365
Time relative to start of operation [min]
Time relative to start of the operation [min]
arterial pH
7,45
7,40
7,35
7,30
7,25
7,20
0,00
-60
a
b
-30
a
0
a
b
b
b
a
15
b
a
b
30
b
a
b
45
b
a
b
65
b
95
a
a
b
125
ab
185
INH
INJ
EPI
group effect: p = 0.0036
time effect: p < 0.0001
time x group effect: p < 0.0001
a
b
a
b
365
ab
Pulmonary Shunt [%]
45
40
35
30
25
20
15
10
5
0
-60
-30
b
0
a
b
15
a
b
b
30
45
65
time effect: p = 0.0773
group effect: p = 0.0135
time x group effect: p = 0.0808
95
125
INH
INJ
EPI
185
365
Time relative to start of the operation [min]
Time relative to start of the operation [min]
Figure 3 Oxygen saturation (SaO 2 ), arterial partial pressure of carbon dioxide
(p a CO 2 ), arterial pH and pulmonary shunt (Qs/Qt) of calves undergoing umbilical
surgery under inhalation (INH; n=10), injection (INJ; n=10) and high volume caudal
epidural anaesthesia (EPI; n=10). Baseline values (-60) are determined in the
standing calf in the operating theatre. Between -60 and -30 min, calves were
anaesthatised and positioned into dorsal recumbency (light grey underlay). The
surgical period is marked by a dark grey underlay. Symbols with a dot differ
significantly from baseline (p < 0.05). For each given point in time, significant
differences between experimental groups are indicated by different letters.
52

Publikation 2
Tables
dorsal recumbancy after surgery
surgery
sternal recumbancy or standing
before surgery
Group Stand
Parameter (n) Stable - 60 min -30 min 0 min 15 min 30 min 45 min 65 min 95 min 125 min 185 min 365 min P-values
Cortisol INH (10) 5.1 ± 5.1 10.2 ± 6.5 7.5 ± 4.1a 15.2 ± 9.7a 26.5 ± 7.7a 27.6 ± 7.1a 25.9 ± 8.5a 26.2 ± 7.0a 20.1 ± 8.2 10.4 ± 7.0 6.2 ± 4.3 3.5 ± 1.7 group 0.3577
[ng ml -1 ] INJ (10) 6.8 ± 5.1 10.7 ± 6.0 19.8 ± 13.7b 22.3 ± 10.1b 22.1 ± 11.7ab 25.9 ± 10.2ab 25.5 ± 11.3a 26.1 ± 13.5ab 23.3 ± 11.1 10.6 ± 5.6 8.1 ± 4.3 3.6 ± 2.3 time

Publikation 2
Group Stand
Parameter (n ) - 60 min -30 min 0 min 15 min 30 min 45 min 65 min 95 min 125 min 185 min 365 min P-values
Body
temperature
before surgery
dorsal recumbancy
surgery
after surgery
sternal recumbancy or standing
INH (10) 39.3 ± 0.1 39.1 ± 0.2 38.2 ± 0.2a 38.1 ± 0.2a 38.1 ± 0.2a 38.0 ± 0.2a 38.0 ± 0.2a 37.5 ± 0.2a 37.6 ± 0.2a 37.5 ± 0.7a 37.6 ± 0.7a group 0.0458
INJ (10) 39.2 ± 0.1 39.3 ± 0.1 38.8 ± 0.1b 38.7 ± 0.1b 38.7 ± 0.2b 38.7 ± 0.2b 38.7 ± 0.2b 38.2 ± 0.1b 38.1 ± 0.1b 38.2 ± 0.4b 38.1 ± 0.4b time

Publikation 2
before surgery
Group Stand
dorsal recumbancy
surgery
after surgery
sternal recumbancy or standing
Parameter (n ) - 60 min -30 min 0 min 15 min 30 min 45 min 65 min 95 min 125 min P -values
CO INH (10) 10.3 ± 1.7 7.5 ± 1.5 10.3 ± 1.9 11.1 ± 2.1 10.4 ± 1.9 10.1 ± 1.8 9.7 ± 1.87 9.8 ± 2.3 9.5 ± 2.1 group 0.7922
[L·min -1 ] INJ (10) 11.8 ± 1.6 8.0 ± 0.9 10.8 ± 1.9 10.6 ± 2.0 9.6 ± 1.8 9.5 ± 1.7 9.8 ± 1.6 10.6 ± 1.6 10.1 ± 0.5 time

Publikation 3
Publikation 3:
Case report: Spinal cord infarct in a calf after aortic catheter implantation
Jennifer Offinger a, *, Henning Meyer a , Reiner Ulrich b , Andreas Beineke b , Jessica
Fischer a , Cornelia Flieshardt c , Andrea Tipold c , Jürgen Rehage a ,
a Clinic for Cattle, University of Veterinary Medicine Hannover, Foundation,
Bischofsholer Damm 15, D-30173 Hannover, Germany
b Department of Pathology, University of Veterinary Medicine Hannover,
Bünteweg 17, D-30559 Hannover, Germany
c Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation,
Bünteweg 9, D-30559 Hannover, Germany
*Corresponding author:
Offinger J
Tel.:+49 511 856 7302
Fax: +49 511 856 7693
E-mail address: jennifer.offinger@tiho-hannover.de
56

Publikation 3
An 8-week-old healthy female German-Holstein calf weighing 60 kg underwent
aortic catheterization to facilitate an arterial access for continuous monitoring of blood
pressure and serial arterial blood sampling. Aortic puncture was carried out under
ultrasonographic guidance on the non-sedated, standing animal between the left
transverse processes of the third (L3) and fourth (L4) lumbar vertebrae on the lateral
border of the longissimus lumborum muscle 1 . In brief, the puncture site was surgically
prepared and locally anesthetized. After five minutes the skin was pre-punctured
using a 15 G hypodermic needle. Under ultrasonographic guidance, a 120 mm
needle a was percutaneously directed into the vessel and a 45 cm long polyethylene
catheter b was introduced using a modified Seldinger technique. Finally, the needle
was withdrawn, leaving 15 cm of the catheter in the lumen of the abdominal aorta.
The catheter was connected to a Luer-lock adapter c and a three-way stopcock. In
contrast to Offinger et al. (2010) the catheter and the stopcock were kept in medical
ethanol and flushed with saline before use. Approximately 2 minutes after the
catheter was successfully implanted in the aorta and flushed with heparinized d
(10,000 IU heparin x L -1 ) 0.9% sterile saline, the calf’s hind limbs suddenly collapsed,
the calf could not regain an upright position and remained in sternal recumbency.
Repeated efforts to assist the calf into a standing position failed, as pelvic limbs could
not support the weight. However, if lifted and supported under the trunk, the calf
could hop on the thoracic limbs.
On clinical examination, the animal was bright, alert and responsive,
had a normal appetite and could maintain sternal recumbency. Both pelvic limbs
were flexed at the hip joint while the stifle was hyperextended. Heart and respiratory
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Publikation 3
rates, as well as body temperature, were within physiological limits. Cardiac and
pulmonary auscultation identified no abnormalities. While consciousness,
examination of the cranial nerves, forelimb postural reactions and forelimb spinal
reflexes appeared normal, a severe paraparesis with a hyperextensive posture of
both stifle joints and a hyperflexion of the hip joints was noted. The tone of the
quadriceps muscles was normal, whereas the tone of the remaining hind limb
muscles was severely reduced. Both hind legs were warm and femoral pulse was
palpable. Neurological examination 2 of the pelvic limbs revealed bilateral reduced
patellar and absent tibialis cranialis and withdrawal reflexes. On exterting pressure
onto the medial areas of the pelvic limb with hemostats, superficial and deep pain
perception was present. However, application of the same noxious stimuli to the
caudal and lateral areas of the distal extremities caused no pain reaction. The
perineal reflex was also absent, the tail was atonic and analgesic, and the bladder
was distended and had to be expressed manually. Haematology and blood
biochemistry results, including serum creatine kinase activity, were considered as
unremarkable in the calf.
Neuroanatomically, the absence of superficial and deep pain sensation in the
area innervated by the sciatic and the pudendal nerves, alongside normal reflexes in
the area innervated by the saphenous nerves suggested a lower motor neuron (LMN)
spinal cord lesion localized between L6 and sacral spinal cord segments. The
decreased patellar reflex was considered to be a result of the hyperextension of the
limbs and, together with pain on the medial side of the leg, indicated that the
segments L4, L5 and the femoral and saphenous nerves were intact. Destruction of
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Publikation 3
the L6, S1 and S2 segments prevented stimulation of alpha-motoneurons of the
sciatic nerves. Therefore, no active flexion of the stifle, tarsus or digits occurred.
Bladder paralysis occurred as a result of the lesion of the sacral segments. At this
point the tentative diagnosis was an acute vascular accident (thromboembolism or
fibrocartilagenous- or air-embolism) involving the spinal cord, causing ischemic
myelopathy and consequentially paraplegia. Treatment with heparin d (100 IU / kg IV),
enrofloxacin e (2.5 mg / kg IV) and carprofen f (1.4 mg / kg SC) was instituted.
Additionally, a singular epidural injection of 8 mg dexamethasone g combined with
1.200.000 IE benzylpenicillin h dissolved in 20 ml sterile isotonic saline was applied.
The following day, magnetic resonance imaging (MRI) i , Magnetom Impact
Plus, 1.0 Tesla, Siemens, Erlangen, Germany) was carried out. The calf was
premedicated with 0.1 mg/kg 2% xylazine j i/m and 2.0 mg/kg ketamine k i/v.
Anaesthesia was maintained with inhalant isoflurane l and oxygen after intubation.
MRI examination was performed about 48 hours after the onset of clinical signs with
the calf in dorsal recumbency. T2-weighted images in sagittal (TR: 4700 ms, TE 112
ms, slice thickness 3 mm) and transverse planes (TR: 3458 ms, TE 96 ms, slice
thickness 3 mm) from the lumbar vertebral column to the sacrum revealed an
intramedullary hyperintense signal abnormality beginning at vertebral body L4. This
lesion occurred mainly in the grey matter with a right lateralization. The spinal cord
segments caudally to vertebral body L5 showed a severe hyperintensity of both the
grey and white matter. Additional signal changes (T2 weighted, hyperintense) were
identified at the area of the right sided paralumbar muscles adjacent to the fifth and
sixth lumbar vertebrae.
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Publikation 3
On sagittal and transverse T1-weighted images (TR: 330 ms, TE 12 ms, slice
thickness 3 mm) the described intramedullary lesion was normointense, while the
muscular abnormality showed a mildly hypointense signal. After the administration of
contrast-medium m (0.2 mmol/kg IV) no pathological enhancement of the spinal cord
but missing physiological enhancement of the described paraspinal muscle and the
body of the fifth lumbar vertebra was present. Gradient-echo magnetic resonance
images (TR: 880 ms, TE 26 ms, slice thickness 3 mm) in transverse plane provided
an hyperintensity of the changed spinal cord parenchyma, whereas the described
paraspinal musculature showed an inhomogeneous hyperintens signal with multifocal
hypointense areas as an indication of necrosis within this muscle group. Altogether,
MRI findings supported the clinical differential diagnosis and indicated profound focal
ischemic necrosis, particularly of the grey matter in the caudal lumbar and cranial
sacral segments of the spinal column.
Despite intense physical therapy and continuation of medication for one week,
the calf’s ability to stand did not improve. In consideration of the poor prognosis and
in consent of animal welfare, the calf was thus euthanized and submitted for postmortem
examination.
Pathological examination revealed a mild to moderate, focal subacute
hematoma with necrosis, mineralization, resorptive lymphohistiocytic inflammation,
hemosiderosis and granulation-tissue formation within the muscular and
retroperitoneal tissues along the puncture channel and focally surrounding the
abdominal aorta. On the left side of the abdominal aorta, on the level of the 4 th
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Publikation 3
lumbar vertebral body, a punctual lesion of less than 1 mm in diameter designated
the puncture site. A small arterial thrombus was firmly attached to the inner surface of
the contralateral vessel wall on an area of approximately 5 mm in diameter and
protruded 1-2 mm into the lumen. Microscopic examination of the arterial thrombus
displayed ongoing organization characterized by infiltrating macrophages
occasionally containing intracytoplasmic brown granular pigment (hemosiderin),
capillary sprouts and fibroblasts. Gross examination of the spinal cord revealed a
locally extensive bilateral malacia and focal hemorrhage of the grey matter extending
from the 4 th lumbar spinal nerve root to the caudal end of the sacral spinal cord
(Figure 2). Microscopically, sections of the affected spinal cord segment contained
extensive bilateral malacia of the grey matter and the adjacent central parts of the
white matter (Figure 3), characterized by necrotic neurons and glial cells,
disintegration of neuropil, myelin sheaths and axons, as well as a peripheral zone of
intercellular edema, multifocal perivascular hemorrhages and infiltrating
macrophages and fewer lymphocytes. Many macrophages / microglia displayed an
enlarged size and foamy cytoplasmic change (“gitter cells”) indicative of phagocytotic
activity. The arteria (A.) spinalis ventralis, and multiple other small to medium sized
arterial vessels (Aa. sulcocomissurales, Aa. radicularis dorsalis; multiple rami
marginales within the white matter) ranging from the area of the 4 th lumbar spinal
nerve root to the caudal end of the sacral cord displayed a multifocal partial to total
occlusion of the vessel lumina by fibrin-rich thrombi, displaying multifocal attachment
to the vessel walls with endothelial necrosis and loss, whereas they exhibited no
contact to the vessel walls in other areas. These thrombi displayed signs of
organization characterized by surface re-endothelization, hyaline change of the fibrin,
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Publikation 3
formation of internal clefts and sinusoid spaces filled by erythrocytes and encased
necrotic white blood cells (Figure 4). A detailed examination of the affected spinal
cord area employing serial histologic sections with an interval of approximately 6 mm
revealed no embolized exogenous particles, skin or soft-tissue pieces within the
vessels. Furthermore, no mucopolysaccarides or chondroid material, were detected
by alcian blue special staining.
There was a moderate focal ischemic necrosis with mineralization, resorptive
inflammation and granulation tissue formation in the right sided paralumbar
musculature, medial of the tuber coxae, possibly representing a second focus of a
primarily arterial thrombotic lesion. Additionally, the urinary bladder displayed mild
dilatation and a mild multifocal subacute lymphoplasmacytic cystitis. The latter
changes were interpreted as a consequence of a neurological impairment of bladder
function as a sequela of the myelomalacia. The final pathomorphological diagnosis of
a subacute thromboembolic arterial infarct of the lumbar and sacral spinal cord with
ischemic myelomalacia most likely originating from an arterial thrombus within the
lumbar aorta contralateral to the arterial puncture site supported the tentative clinical
diagnosis and the findings in MRI of an ischemic myelopathy of the caudal lumbar
and sacral spinal cord segments. The majority of spinal cord grey matter is supplied
by the ventral spinal artery and, as it has the highest area of vascularity, is most
susceptible to ischemia.
Ischemic myelopathy as a result of acute spinal cord infarction caused by
fibrocartilagineous emboli has been described in several large animal species
including pigs 3 , sheep 4 , a calf 5
and horses 6,7 . Aortic thrombosis and subsequent
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Publikation 3
embolization has been identified as another major cause of spinal cord ischemia. In
cats and man, the formation of arterial thrombi is strongly associated with underlying
cardiovascular and thromboembolic diseases 8
or abdominal aortic operation 9 . In
calves and horses the origin of occluding thrombi is less clear 10,11 . In the few
described cases, predisposing factors associated with the formation of thrombemboli
were identified to be valvular endocarditis, bacterial endotoxins 12 , immune
complexes 13 , disruption of laminar blood flow 14 , injury to vascular endothelium and
alteration in the coagulability of the blood 15 . However, the clinical and post mortem
examination provided no informative basis for such alterations being the cause for
the ischemic myelopathy and the chronology of events appears highly indicative of a
direct causal relationship to the catheterization process. The application of a recently
published classification system for forensic histological age determination of
thromboses and embolisms in human fatal pulmonary thromboembolism 16 revealed
that both, the aortic arterial thrombus and the spinal cord thrombemboli display
changes characteristic for a 1-7 week-old process, including infiltrating endothelial
sprouts, fibroblasts, and macrophages containing hemosiderin, coalescing ribbons of
fibrin with entrapped necrotic white blood cells, and re-endothelization of the
thrombus surface (phase II; 2 nd to 8 th week) which is in accordance with the one week
period between catheterization and necropsy of the present case.
Trauma to the vascular endothelium at insertion, caused by the needle, the
catheter tip or the guide wire exposes luminal blood to collagen and tissue factors
and may have stimulated thrombus formation through the activation of the platelet
and coagulation cascade. This was further exacerbated by the alterations in normal
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Publikation 3
blood flow 15 caused by the indwelling catheter. In a murine model, using real-time in
vivo imaging, thrombus formation was demonstrated 15-20 seconds after laserinduced
endothelial injury 17 . In hamsters, thrombi were detected 8 ± 1.1 min after a
trauma was set to the carotid artery by crushing the exposed vessel with a clamp.
The formed thrombi gradually embolized and disintegrated 15 ± 2.1 min after
traumatization 18 . As the onset of neurological symptoms in this case was within
minutes of the puncture, the detachment of thrombemboli must have occurred very
shortly after the procedure. Therefore, even if taking into account inter-species
variances in hemostasis, it appears unlikely that a thrombembolus originating from
endothelial damage contralaterally to the puncture site disintegrated that rapidly and
consequentially led to the infarction of the spinal vessels.
Cutaneous, subcutaneous or muscular material accumulated in the lumen of
the needle may have been introduced into the abdominal aorta whilst threading the
catheter into the vessel. Emboli may have travelled with the aortic bloodstream into
arterial branches supplying the vertebrae. The occurrence of skin tissue emboli
originating from needle punctures 19,20 or catheter fragment embolization have been
reported in studies in man 21,22 . Even though the temporal sequence would support
these explanations, skin tissue or a polyurethrane fragment would have been
detected macroscopically or histologically. Moreover, it appears unlikely that these
emboli would cause multiple arterial embolization.
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Publikation 3
The three-way stopcock and the catheter were immersed in ethanol before
use. The multiple thrombi in the vessels of the spinal cord may have formed by
remnants of ethanol within the lumen of the stopcock despite flushing with saline
before connection to the catheter. After the catheter was inserted and connected to
the stopcock on flushing with saline these remnants may have entered the aortic
blood stream or, depending on the location of the catheters’ tip, directly into spinal
vessels. Due to the sclerosing properties and local toxic effects related to its protein
denaturant and hydroscopic properties, ethanol is widely used as embolizing agent
for large area tissue destruction 23 . Therapeutic transcatheter arterial embolization is
an established procedure to treat neoplasms and arteriovenous malformations in a
variety of tissues. Major complications described in transcatheter arterial
embolization are spinal cord infarction and distal embolization of particles into the
aorta and its branches 24 . To achieve renal infarction in dogs, 0.2 ml/kg body weight of
pure ethanol was injected into the renal artery, although the authors indicate that a
lower concentration and amount would suffice 25 . It appears unlikely that remnants of
alcohol within the introduced catheter play a role in the pathogenesis of the
thrombembolus since the catheter was flushed with saline before insertion as well as
by aortic blood directly after insertion due to the high arterial blood pressure.
Another cause of embolization may have been small air bubbles, introduced
into the vessel on flushing the catheter. In arterial vessels, cerebral air emboli due to
a patent foramen ovale originating from central venous catheters and resulting in
neurologic manifestations have been described in man 26,27 . However, special
attention was paid on removal of possible air bubbles within the used syringe prior to
65

Publikation 3
flushing with hepatinized saline, thus, it appears unlikely that air bubbles were
intoduced into the aorta. Furthermore, during catheterization, the high blood pressure
within the abdominal aorta immediately forced blood out of the catheter thus resulting
in an immediate retrograde blood flow which did not allow for air bubbles to be
introduced.
The etiology of the multiple thromboembolic arterial infarct of the spinal cord in
the described case is not definitely proven, but it appears highly likely that embolism
was caused by ethanol or possibly air bubbles since histopathological examination
revealed no embolic material. Thus, in order to reduce the risk of thromboembolism
after catheterization of vessels, implementation of sterilized catheter material is
recommended or thorough flushing before use must be guaranteed.
Footnotes
a TSK-Supra Cannula, length 120 mm, OD 2 mm, Tochigi, Japan
b
Polyethylene tube, AD 1.27 mm, Kleinfeld Labortechnik, Gehrden, Germany
c Teflon AD 1.5 mm, Walter Veterinär Instrumente e. K., Baruth/Mark,
Germany
d Heparin-calcium-25000-ratiopharm, Ratiopharm GmbH, Ulm, Germany
e Baytril, Bayer Vital GmbH, Leverkusen, Germany
f Rimadyl Cattle, Pfizer Pharma GmbH, Karlsruhe, Germany.
g Dexamethason-Injektionslösung,CP-Pharma, Burgdorf, Germany
h Penicillin-G-Natrium, Bela-Pharm, Germany
i Magnetom Impact Plus, 1.0 Tesla, Siemens, Erlangen, Germany
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Publikation 3
j Rompun, Bayer Vital GmbH, Leverkusen, Germany
k
Ketamin 10%, Selectavet GmbH, Weyarn-Holzolling, Germany
l Isofluran-Baxter®, Baxter Deutschland GmbH, Unterschleißheim, Germany
m Gadolinium-Dimeglumine, GdDTPA, Magnevist®, Schering Deutschland
GmbH, Berlin, Germany
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References:
1. Offinger J. Percutaneous, ultrasonographically guided technique of
catheterization of the abdominal aorta in calves for serial blood sampling and
continuous arterial blood pressure measurement. Res Vet Sci
2010:doi:10.1016/j.rvsc.2010.1007.1016.
2. Constable PD. Clinical examination of the ruminant nervous system. Vet Clin
North Am Food Anim Pract 2004;20:185-214.
3. Tessaro SV, Doige CE, Rhodes CS. Posterior paralysis due to fibrocartilaginous
embolism in two weaner pigs. Can J Comp Med 1983;47:124-126.
4. Jeffrey M, Wells GA. Multifocal ischaemic encephalomyelopathy associated with
fibrocartilaginous emboli in the lamb. Neuropathol Appl Neurobiol 1986;12:415-
424.
5. Landolfi JA, Saunders GK, Swecker WS. Fibrocartilaginous embolic myelopathy
in a calf. J Vet Diagn Invest 2004;16:360-362.
6. Taylor HW, Vandevelde M, Firth EC. Ischemic myelopathy caused by
fibrocartilaginous emboli in a horse. Vet Pathol 1977;14:479-481.
7. Fuentealba IC, Weeks BR, Martin MT, et al. Spinal cord ischemic necrosis due to
fibrocartilaginous embolism in a horse. J Vet Diagn Invest 1991;3:176-179.
8. Laste NJ, Harpster NK. A retrospective study of 100 cases of feline distal aortic
thromboembolism: 1977-1993. J Am Anim Hosp Assoc 1995;31:492-500.
9. Rosenthal D. Spinal cord ischemia after abdominal aortic operation: is it
preventable? J Vasc Surg 1999;30:391-397.
10. Rolfe DL. Aortic thromboembolism in a calf. Can Vet J 1977;18:321-324.
11. Maxie MG, Physick-Sheard PW. Aortic-iliac thrombosis in horses. Vet Pathol
1985;22:238-249.
12. D'Angelo A, Bellino C, Alborali GL, et al. Aortic thrombosis in three calves with
Escherichia coli sepsis. J Vet Intern Med 2006;20:1261-1263.
13. Louis J, Salmon J, Betz C. [Pathogenesis of the intravascular coagulation
syndrome induced by immunologic reactions: role of the antigen-antibody ratio
in the activation of the phenomenon]. C R Seances Soc Biol Fil 1971;165:1484-
1487.
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14. Goldsmith HL. The flow of model particles and blood cells and its relation to
thrombogenesis. Prog Hemost Thromb 1972;1:97-127.
15. Morley PS, Allen AL, Woolums AR. Aortic and iliac artery thrombosis in calves:
nine cases (1974-1993). J Am Vet Med Assoc 1996;209:130-136.
16. Fineschi V, Turillazzi E, Neri M, et al. Histological age determination of venous
thrombosis: a neglected forensic task in fatal pulmonary thrombo-embolism.
Forensic Sci Int 2009;186:22-28.
17. Falati S, Gross P, Merrill-Skoloff G, et al. Real-time in vivo imaging of platelets,
tissue factor and fibrin during arterial thrombus formation in the mouse. Nat Med
2002;8:1175-1181.
18. Stockmans F, Stassen JM, Vermylen J, et al. A technique to investigate mural
thrombus formation in small arteries and veins: I. Comparative morphometric
and histological analysis. Ann Plast Surg 1997;38:56-62.
19. Andrew JH. Pulmonary skin embolism: a case report. Pathology 1976;8:185-187.
20. Donhuijsen K, Schmidt U. [Iatrogenic skin-tissue embolism in the lung]. Schweiz
Med Wochenschr 1983;113:833-834.
21. Doering RB, Stemmer EA, Connolly JE. Complications of indwelling venous
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1967;114:259-266.
22. Surov A, Buerke M, John E, et al. Intravenous port catheter embolization:
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24. Miller FJ, Jr., Mineau DE. Transcatheter arterial embolization-major complications
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25. Ellman BA, Green CE, Eigenbrodt E, et al. Renal infarction with absolute ethanol.
Invest Radiol 1980;15:318-322.
26. Eichhorn V, Bender A, Reuter DA. Paradoxical air embolism from a central
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27. Fathi AR, Eshtehardi P, Meier B. Patent foramen ovale and neurosurgery in
sitting position: a systematic review. Br J Anaesth 2009;102:588-596.
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70

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Figure 1: magnet resonance tomography: T2-weighted images in
transverse planes (TR: 3458 ms, TE 96 ms, slice thickness 3 mm) at vertebral
body L5. “x” labels an intramedullary hyperintense signal abnormality in the
grey matter with a right lateralization. “o” labels hyperintense signal changes in
the area of the right sided paralumbar muscles; R = right sided.
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Figure 2: Spinal cord. Bovine. Transversal section of the lumbar spinal cord
reveals a focally-extensive bilateral ischemic malacia of the grey matter (stars)
surrounded by a rim of edema and hemorrhage.in the adjacent white matter
(arrows). Furthermore a thrombembolus is present within the arteria spinalis
ventralis (arrowhead). Df = dorsal funiculus of the white matter; dh = dorsal
horn of the grey matter; dr = dorsal spinal nerve root; lf = lateral funiculus of
the white matter; vh = ventral horn of the grey matter; vr = ventral spinal nerve
root.
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Publikation 3
Figure 3: Spinal cord. Bovine. Light microscopic examination of the
lumbar and sacral spinal cord reveals a marked subacute ischemic malacia of
the grey matter characterized by disintegration of the neuropil, and necrotic
neurons (arrow), surrounded by a peripheral rim of edema (stars), and
infiltrating macrophages / microglia and gitter cells (arrowhead) in the adjacent
white matter. Gm = grey matter; wm = white matter. HE. Bar = 200 µm.
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Publikation 3
Figure 4: Arteria spinalis ventralis. Bovine. Light microscopy of a
thrombembolus displaying signs of organization characterized by surface reendothelization
(arrows), hyaline change of the fibrin (stars), and encased
necrotic white blood cells. Tm = tunica media; vl = remaining vessel lumen.
HE. Bar = 100 µm.
74

Übergreifende Diskussion
Übergreifende Diskussion
Ziel dieser Studie war es, drei Anästhesieprotokolle hinsichtlich ihrer hormonellmetabolischen
Schmerzreaktion sowie kardiovaskulärer und hämodynamischer
Auswirkungen während einer Nabeloperation beim Kalb zu untersuchen. Das
markanteste Ergebnis dieser Arbeit ist, dass die hohe Epiduralanästhesie mit Xylazin
und Procain in Kombination mit einer Lokalanästhesie sowie der präoperativen
Applikation eines nichtsteroidalen Antiphlogistikums (NSAIDs) eine im Vergleich zur
Inhalationsnarkose, welche als „Goldstandard“ gilt, ebenso überzeugende Form der
gleichmäßig anhaltenden Schmerzausschaltung für die Nabeloperation des Kalbes
darstellte (Kapitel 2). Die Injektionsnarkose mittels Xylazin und Ketamin stellte sich
hinsichtlich der analgetischen Potenz und Narkosetiefe als schwer steuerbar sowie
unzuverlässig heraus. Letzteres entsprach nicht den Erwartungen, da die für diese
Studie gewählte Dosierung von 0.2 mg kg -1 Xylazin und 5.0 mg kg -1 Ketamin im
Bereich der üblichen Empfehlungen von Waterman (1981), Thurmon (1986) sowie
Carroll und Hartsfield (1996) lag, um beim Rind eine ausreichende Analgesie für
chirurgische Interventionen zu erreichen. Bei niedrigerer Dosierung (0,088 mg kg -1
Xylazin und 4,4 mg kg -1
Ketamin) machten bereits Rings und Muir (1982) die
Erfahrung einer beim Rind unzureichend herbeigeführten Analgesie. Mit dieser
Studie konnte wissenschaftlich belegt werden, dass die Epiduralanästhesie durch die
einfache und kostengünstige Anwendbarkeit eine überzeugende Anästhesiemethode
für abdominalchirurgische Eingriffe bei Kälbern darstellt, die der Inhalationsnarkose
ebenbürtig und der Xylazin/Ketamin Injektionsnarkose deutlich überlegen ist
75

Übergreifende Diskussion
Basierend auf der Beurteilung von typischen schmerzbedingten Verhaltensweisen
wurde in dieser Studie die Epiduralanästhesie der Inhalationsnarkose untergeordnet,
jedoch der Injektionsnarkose überlegen angesehen. Diese Einreihung muss jedoch
differenzierter betrachtet werden: Die Epiduralanästhesie wird den Lokalanästhesien
zugeordnet, da sie nicht zur Bewusstlosigkeit des Tieres führt. Die systemische
Resorption von epidural appliziertem Xylazin führt zwar zu systemischer Wirkung mit
sedativen Effekten (Lee et al., 2001), ist aber dennoch nicht mit der
ketaminbedingten funktionellen Entkopplung zwischen dem thalamo-neokortikalen
und dem limbischen System (Kochs et al., 1988) oder der zur Bewusstlosigkeit
führenden Wirkung des Isoflurans zu vergleichen. Während die
Bewegungsunfähigkeit unter der Inhalationsnarkose auf der muskelrelaxierenden
und hypnotischen Wirkung des Isoflurans basiert, führt die hier durchgeführte hohe
Epiduralanästhesie naturgemäß lediglich zur Paralyse der Hintergliedmaßen. Kälber
unter Epiduralanästhesie verfügen jedoch cranial der Anästhesie über das
vollständige Verhaltensrepertoire und können jede Form des Unwohlseins, sei es
operationsbedingt oder durch die ungewohnte Fixierung in Rückenlage, zu erkennen
geben. Damit mögliche Spontanbewegungen von schmerz-induzierten
Verhaltensäußerungen unterschieden werden konnten, erfolgten Aufzeichnungen nur
bei Reaktionen auf zuvor definierte und erfahrungsgemäß schmerzhafte operative
Manipulationen (z.B. Haut- und Muskelinzisionen). Dennoch ist im Fall der
epiduralanästhesierten Tiere die Abgrenzung von wirklichen Schmerzreaktionen und
dem Reflex, sich aus einem ungewohnten propriozeptiven Zustand zu befreien,
kaum zu unterscheiden. Ferner ist bekannt, dass Isofluran nur geringe analgetische
Wirkung besitzt und daher stets mit der Applikation von Analgetika kombiniert
76

Übergreifende Diskussion
werden muss (Pascoe, 2000). Erfolgt dies nur unzureichend oder womöglich nicht,
würde die Isofluran-induzierte Inhalationsnarkose dennoch dem betroffenem Kalb
keinen Ausdruck von Schmerz durch Verhaltensänderungen erlauben. Die im Mittel
leicht erhöhten Scores der Kälber unter Epiduralanästhesie im Vergleich zur
Inhalationsnarkose lassen sich dadurch erklären, werfen aber gleichzeitig die Frage
auf, inwiefern diese unterschiedlichen Anästhesietechniken hinsichtlich der
intraoperativen Verhaltensbeurteilung überhaupt verglichen werden können.
Verhaltensbeobachtungen zur Beurteilung von Schmerzzuständen, die durch
Übertragung in ein VAS oder NRS System zwar statistisch leicht auswertbar werden,
stellen immer eine subjektive Beurteilung dar. Sie gelten als sehr sensitiv und sind
daher auch nicht verzichtbar. Es ist aber stets ratsam, diese mit objektiven,
messbaren Parametern zu kombinieren (Anil et al., 2002). Zu diesen gehört die
hormonelle Stressantwort auf einen nozizeptiven Reiz, der beispielsweise durch ein
operatives Trauma hervorgerufen wird.
Stress und Traumata führen durch die Aktivierung der Hypothalamus-Hypophysen-
Nebennieren-Achse zur Erhöhung von Katecholamin- und Kortisolkonzentrationen
(Kehlet, 1991, Mellema et al., 2006, Mellor et al., 2002). Die
Plasmacortisolkonzentrationen stiegen bei den Versuchskälbern bereits mit dem
Verbringen in den Operationsraum, erneut mit der Rückenlagerung und wieder mit
Beginn der Operation an. Im Unterschied zu Verhalten der Plasmacortisolspiegel
konnte erst mit Beginn der chirurgischen Eröffnung der Bauchhöhle eine Erhöhung
der mittleren Epinephrinwerte der Kälber beobachtet werden. Zu diesem Zeitpunkt
erhöhten sich die Epinephrinwerte um ein 20- bis 30-faches gegenüber den
77

Übergreifende Diskussion
Basalwerten, wenn auch nur kurzfristig. Sie fielen rasch im Verlauf des operativen
Eingriffes, blieben aber selbst eine Stunde post-operationem gegenüber dem
Basiswert leicht erhöht. Der erhebliche Anstieg in den Plasma-Catecholamin-
Konzentrationen deutet auf eine inkomplette nozizeptive, sympathische oder
endokrine Blockade aller drei Anästhesieverfahren hin. Auch die bei allen Kälbern
zusätzlich durchgeführte lokale rhomboide Umspritzung des Nabels mit
Lokalanästhetika konnte diese Reaktion offensichtlich nicht unterdrücken. Es ist
bekannt, dass eine operationsbedingte Stressantwort nie komplett durch eine
Narkose unterdrückt werden kann, da eine lokale Reaktion an der Schnittstelle nicht
verhindert werden kann (Desborough, 2000, Imura et al., 1991). Tatsächlich zeigten
Studien an Ponys und Rindern, dass die Inhalationsnarkose per se eine maximale
Stressantwort hervorruft, selbst wenn kein nozizeptiver Stimulus oder Gewebstrauma
auf das Tier einwirkt (Taylor, 1998, Anderson and Muir, 2005).
Mit dem multimodalen Ansatz in dieser Studie, d.h. der kombinierten Anwendung von
Analgetika verschiedener Substanzklassen, sollten nozizeptive Reize auf möglichst
allen Ebenen des schmerzleitenden Systems gehemmt werden. Aus der
Humanmedizin ist bekannt, dass allein die Epiduralanästhesie eine komplette
Suppression der endokrinen Stressantwort induzieren kann, allerdings beschränkt
sich diese Aussage auf Eingriffe caudal des Nabels. Um eine komplette
sympathische und somatische Blockade dieses Operationsgebietes zu erreichen, die
nicht nur nozizeptive, sondern auch nicht-nozizeptive Afferenzen umfasst, sollte laut
Engquist et al. (1977) die Epiduralanästhesie eine Ausdehnung von Th4 bis S5
aufweisen. In einer Studie von Meyer et al. (2007), welcher mittels epiduraler
78

Übergreifende Diskussion
Applikation eines Kontrastmittels dessen Ausbreitung innerhalb des Epiduralspaltes
untersuchte, wurde mit einem Volumen von 0,4 ml kg -1 KGW eine kraniale Migration
bis zu Th12 beobachtet. Offenbar wurde in der vorliegenden Studie trotz epiduraler
Applikation eines größeren Volumens von 0,6 ml kg -1 KGW eine Ausbreitung der
Anästhetika bis Th4 ebenfalls nicht erreicht, da eine komplette sympathische und
somatische Blockade des Operationsfeldes anhand der hormonellen Stressantwort
nicht erkennbar war. Da jedoch mit der Applikation größerer Volumina die Gefahr
steigt, den N. phrenicus, welcher seinen Ursprung im fünften bis siebten
Zervikalsegment hat, mit in die Blockade einzuschließen und somit eine motorische
Blockade der rumpfnahen Atemmuskulatur und des Zwerchfells zu verursachen, war
eine weitere Volumenerhöhung ohne vorherige Prüfung der Verträglichkeit nicht
vertretbar. Weiterhin wäre in diesem Fall eine Intubation und Beatmungseinrichtung
unerlässlich, was wiederum dem praktischen Motivationsgrund der Anästhesie
widerspricht.
Die Epiduralanästhesie führte in dieser Studie nicht nur zu einer hoch wirksam
Schmerzausschaltung, sie erwies sich auch als unproblematisch in der
Durchführung. Ein gewisser anästhetikabedingter kardio-respiratorisch depressiver
Effekt wurde durch alle drei Anästhesieprotokolle verzeichnet, jedoch wurden die
signifikant geringsten Auswirkungen auf die Respiration (Atemfrequenz,
Sauerstoffsättigung, pCO 2 , pulmonärer Shunt, pH) und kardiovaskuläre Funktion
(MAP, SVR) bei den epiduralanästhesierten Tieren gemessen. Die Injektionsnarkose
hatte im Gegensatz nicht nur die schwächste analgetische Wirkung, sondern auch
einen klinisch relevanten negativen Effekt auf die Respiration. Im Mittel wurden bei
79

Übergreifende Diskussion
diesen Tieren während der Operation im Vergleich zu den beiden weiteren Gruppen
die niedrigsten arteriellen Sauerstoffsättigungen von deutlich unter 90% gemessen.
Bemerkenswert ist, dass die erforderliche Nachdosierung von 2.5 mg kg -1 Ketamin
bei vier Kälbern trotz konsequent langsamer, intravenöser Verabreichung zu bis zu
zwei minütigen Atemstillständen führte. Aus Sicht der praktischen Durchführung sind
die wiederholten Anästhetika-Gaben der Injektionsnarkose als nachteilig zu
bewerten, da eine wiederholte Applikation unter sterilen Kautelen ein qualifiziertes
Hilfspersonal voraussetzt. Ein solcher gravierender Narkosezwischenfall wie ein
Atemstillstand würde jedoch selbst einen erfahrenen Praktiker intraoperativ in eine
kompromittierende Situation bringen. Eine geringere Dosis zu wählen, wäre
sicherlich eine Möglichkeit, um die Nebenwirkungen zu verringern, jedoch nicht ohne
die Gefahr, dabei gleichzeitig die analgetische Wirkung zu vermindern.
Es wird aus den Ergebnissen geschlussfolgert, dass die Epiduralanästhesie mit
Xylazin und Procain für Operationen am Nabel von Kälbern eine zuverlässige
Schmerzausschaltung herbeiführt. Ferner stellt diese Form der Anästhesie aufgrund
ihrer einfachen Anwendbarkeit, den minimalen unerwünschten Nebenwirkungen und
dem geringen Kostenaufwand bei Nabeloperationen an Kälbern eine hervorragende
Anästhesieform für die Praxis dar. Die Injektionsnarkose mit Xylazin und Ketamin
erscheint schwer steuerbar und damit unzuverlässig für eine gleichmäßige
Schmerzausschaltung. Zudem wird die mit ihr verbundene Atemdepression als
klinisch gravierend eingeschätzt und es ist mit lebensbedrohlichen Komplikationen zu
rechnen. Sie erscheint damit nicht nur unzureichend in ihrer Wirksamkeit, sondern
zudem als unsicher und wird daher zur Anwendung in der Praxis nicht empfohlen.
80

Übergreifende Diskussion
Die Inhalationsnarkose hatte gegenüber der Epiduralanästhesie bei Kälbern
hinsichtlich der Wirksamkeit und Sicherheit keine nennenswerten Vor-, aber auch
keine Nachteile. Beim Vorhandensein entsprechender Gerätschaften ist die
Inhalationsnarkose in der hier geprüften Form eine unstrittig adäquate Methode zur
Schmerzausschaltung.
In dieser Studie wurde die Aorta abdominalis als arterieller Zugang für Blutdruck und
Blutgasmessungen gewählt. Die bekannte Punktionstechnik (Junhold and Schneider,
2002, Weber et al., 1992) wurde durch die Sonographie ergänzt und erfolgte somit
unter visueller Kontrolle (Kapitel 1). Trotz dieser Optimierung wurde bei einem Kalb
eine letztlich tödlich verlaufende Komplikation, ein spinaler Infarkt, beobachtet. Da
spinale Infarkte extrem seltene Ereignisse bei Rindern darstellen und eine
vollständige neurologische Aufarbeitung des Falles möglich war, kann dieser in Form
eines Fallberichts präsentiert werden (Kapitel 3). Die Begebenheit erscheint auch
deshalb berichtenswert, da als Ursache eine Verunreinigung des Punktionsmaterials
mit medizinischem Alkohol nahe lag. Katheter und Zubehör wurden bis zur Punktion
in 70 Vol-% Ethanol gelagert und vor Anwendung mit Kochsalzlösung gespült,
offenbar jedoch nicht ausreichend. Die Lagerung von chirurgischen Instrumenten ist
in der Nutztierpraxis noch immer übliche Praxis. Deshalb ist die Information, dass bei
Verwendung so gelagerten Kathetermaterials, ohne eine vorherige sorgfältige
Spülung, Embolien möglich sind, für die Praxis aber auch für experimentelle
Anwender von besonderer Bedeutung. Dies war die einzige jemals mit der
Aortenpunktion an der hiesigen Klinik vergesellschaftete Komplikation. Da
inzwischen über 100 Kälber auf diese Weise punktiert wurden, wird die
81

Übergreifende Diskussion
Aortenpunktion dennoch als ausreichend sicher angesehen. Zudem wird an der
hiesigen Klinik als Konsequenz auf die beobachtete Komplikation Kathetermaterial
nicht mehr in Alkohol gelagert.
82

Literatur
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85

Zusammenfassung
Jennifer Offinger (2010)
Vergleichende Studie zur Analgesie der Nabelregion mittels Isofluran-
Inhalationsnarkose, Epiduralanästhesie und Injektionsnarkose und zu den
Auswirkungen dieser drei Methoden auf die intraoperativen Schmerzparameter und
das Herzkreislaufsystem bei Kälbern
Zusammenfassung
In einer vergleichenden Studie wurden die Auswirkungen dreier Anästhesieformen
(Inhalations-, Injektions- und Epiduralanästhesie) auf die Analgesie sowie auf
kardiorespiratorische- und endokrin-metabolische Parameter während einer
Nabeloperation beim Kalb geprüft.
Die Untersuchungen wurden an 30 Kälbern (7 Kuh- und 23 Bullenkälber) der Rasse
Holstein-Friesian aus dem Bestand der Klinik für Rinder der Tierärztlichen
Hochschule Hannover, mit einem durchschnittlichen Alter von 45,9 ± 6,4 Tagen und
einem mittleren Köpergewicht von 66,1 ± 6,2 kg, durchgeführt. Die Kälber wurden
randomisiert in drei Gruppen mit je 10 Tieren eingeteilt. Die Narkose der Kälber der
Gruppe INH wurden mit Xylazin (0,1 mg kg -1 IM), gefolgt von Ketamin (2,0 mg kg -1 IV)
eingeleitet, und durch eine Isofluran-Inhalation mit einer Sauerstoffflussrate von 2 L
min -1 aufrechterhalten. Gruppe INJ erhielt 0,2 mg kg -1 Xylazin IM sowie 5,0 mg kg -1
Ketamin IV, wobei die Narkose durch regelmäßige Nachdosierungen von Ketamin in
10-15minütigen Abständen mit der Hälfte der Initialdosis aufrechterhalten wurde.
Kälber der Gruppe EPI bekamen 0,2 mg kg -1 Xylazin, welches mit 2%igem Procain
zu einem Gesamtvolumen von 0,6 ml kg -1 verdünnt wurde, kaudal epidural appliziert.
Die rhomboide Infiltration der Schnittlinie erfolgte mit 20 mL 2%igem Procain.
Zusätzlich erhielten alle Kälber 30 min vor Operationsbeginn eine Applikation von 2,2
mg kg -1 Flunixin IV.
Alle Parameter wurden präoperativ am stehenden und (nach Anästhesieeinleitung)
am liegenden Tier ermittelt. Intraoperativ fanden die Messungen in 15minütigen
86

Zusammenfassung
Abständen statt (Tier in Rückenlage). 30, 60 und 120 Minuten post operationem
wurde in vom Tier selbst gewählter Lage (Stand oder Brustlage) gemessen. Die
endokrine Stressantwort wurde durch regelmäßige Bestimmung von Epinephrin-,
Norepinephrin- und Kortisol-Konzentrationen aus venösen Blutproben bestimmt. Eine
Visuell Analoge Skala (VAS) wurde angewandt um die intraoperative Nozizeption zu
beurteilen. Mit Hilfe eines Herzkatheters, eines Aortenkatheters und der
Blutgasanalyse wurden die Herzkreislauffunktionen kontinuierlich überwacht.
Die Epiduralanästhesie hatte, gemessen an Cortsiol und Katecholamin-
Konzentrationen, intraoperativ eine signifikant geringere endokrine Stressantwort als
die Inhalations- und Injektionsnarkose zur Folge. Die höchsten VAS-Werte wurden in
Gruppe INJ aufgezeichnet, gefolgt von Gruppe EPI und Gruppe INH. Intraoperativ
sank der Sauerstoffpartialdruck (PaO 2 ) in Gruppe INJ signifikant ab. Kälber der
Gruppen INH und INJ entwickelten im Laufe der Operation eine Hypertonie, eine
respiratorische Azidose (gekennzeichnet durch einen hohen arteriellen pH und
Kohlendioxidpartialdruck), sowie einen erhöhten systemischen Gefäßwiderstand.
Mit den Ergebnissen dieser Studie konnte belegt werden, dass die hohe
Epiduralanästhesie aus einer Kombination aus Xylazin und Procain, zusammen mit
einer rhomboiden Infiltration der Schnittstelle und der präoperativen Applikation von
Flunixin eine praktikable, kostengünstige und sichere Anästhesiemethode bietet, um
Kälber einer Nabeloperation zu unterziehen. Im Vergleich zur in dieser Studie
geprüften Inhalations- und Injektionsnarkose zeigten die epiduralanästhesierten Tiere
eine verminderte endokrine Stressantwort und die gemessenen kardio-pulmonären
Parameter wurden durch die Anästhesie kaum beeinträchtigt.
Das bisherige Verfahren der direkten Aortenpunktion am stehenden Tier wurde in
dieser Studie durch die ultrasonographische Kontrolle ergänzt. Bei 29 Kälbern
konnten innerhalb 24 Stunden nach der so durchgeführten Aortenpunktion keine
klinischen Anzeichen von Anämie oder Entzündung festgestellt werden. Es war
weiterhin über die nächsten 5 Tage weder eine lokale Entzündungsreaktion, noch ein
87

Zusammenfassung
signifikanter Anstieg von Leukozyten erkennbar. Zwar war durch den dirketen
Blutverlust bei der Punktion ein signifikanter Abfall an Erythrozyten, Hämoglobin,
Hämatokrit und Gesamteiweiß zu vermerken, jedoch blieben diese Werte innerhalb
der Referenzwerte. Die oftmals als riskant eingestufte Methode der direkten
Aortenpunktion ist demnach durch die ultrasonographische Kontrolle bedeutend
effizienter und sicherer geworden. Dennoch ist darauf hinzuweisen, dass die
Punktion arterieller Gefäße stets mit dem Risiko einer Embolie verbunden ist, daher
ist der zusätzliche Nutzen eines invasiven gegenüber eines nicht-invasiven
Verfahrens für die Datenerhebung abzuwägen. In einem von 102 Kälbern trat bei
einem Kalb eine Paraplegie aufgrund multipler Embolien spinaler Gefäße des
Lendenmarkes mit folgender ischämische Myelopathie. Trotz
magnetresonanztomographischer- und pathologisch-histologischer Untersuchung
bleibt die genaue Embolieursache in diesem Fall ungeklärt. Es erscheint aber am
naheliegendsten, dass eine Verunreinigung des Kathetermaterials sowie des
Zubehörs die Embolie auslöste.
88

Summary
Jennifer Offinger (2010)
Comparison of isoflurane inhalation anaesthesia, injection anaesthesia and high
volume caudal epidural anaesthesia in calves; metabolic, endocrine and
cardiopulmonary effects
Summary
In a prospective, randomised study, the effects of three anaesthetic regimes
(inhalation-, injection- and high volume caudal epidural anaesthesia) were compared
regarding analgesic qulatity, cardiorespiratory effect and endocrine-metabolical
parameters in calves undergoing umbilical surgery.
Thirty Holstein-Friesian calves (7 female, 23 male) aged 45.9 ± 6.4 days with a mean
body weight of 66.1 ± 6.2 kg were included in the study. Calves were randomly
allocated to three groups: The inhalation-group (INH) received isoflurane in oxygen
after induction of anaesthesia with 0.1 mg kg -1 xylazine IM and 2.0 mg kg -1 ketamine
IV, the injection-group (INJ) was treated with 0.2 mg kg -1 xylazine IM and 5.0 mg kg -1
ketamine IV injection, redosed every 10-15 min with half the initial dose of ketamine,
while the epidural-group (EPI) underwent a high volume caudal epidural anaesthesia
of 0.2 mg kg -1 xylazine, diluted to a final volume of 0.6 ml kg -1 with procaine 2%. All
calves received a periumbilical infiltration with local anaesthetic and a pre-emptive
application of flunixine IV (2.2 mg kg -1 ).
Preoperative parameters were initially determined in the standing calf. After induction
of anaesthesia, measurements took place in 15 minute intervals with the animal
restrained in dorsal recumbency. During the final measurements taken 30, 60 and
120 minutes after completing the surgery, animals were free to choose standing
position or sternal recumbency.
The endocrine stress response was determined through analysis of epinephrine,
norepinephrine and cortisol concentrations. A visual analogue scale (VAS) was
89

Summary
applied to monitor intraoperative nociception. Additionally, with the help of an aortic
catheter and a Swan-Ganz catheter, cardiopulmonary variables and arterial blood
gases were continuously monitored.
Compared to inhalation- and injection anaesthesia, the high volume caudal epidural
anaesthesia resulted in an intraopertively reduced stress response as determined by
cortisol and catecholamine concentrations. The highest VAS-scores were recorded
for Group INJ, followed by Group EPI and Group INH. During the course of the
operation, partial pressure of oxygen (PaO 2 ) in Group INJ was significantly
decreased. Calves of Groups INH and INJ developed hypertonia and respiratory
acidosis, as well as an increased systemic vascular resistance.
The results of the study indicate that the high volume caudal epidural anaesthesia,
consisting of xylazine and procaine, combined with a periumbilical infiltration of local
anaesthetic and a preoperative NSAID-application provides a practical, inexpensive
and safe anaesthetic protocol for calves undergoing umbilical surgery. Compared to
inhalation and injection anaesthesia, a reduced endocrine stress response was
observed and cardiopulmonary variables were scaresly affected.
The current method of direct aortic puncture on the standing, unsedated animal was
improved by adding ultrasonographical control. Within 24 hours of puncture, no
clinical signs of anaemia or inflammation were observed in 29 punctured animals.
Furthermore, in the following four days, neither local inflammation, nor significant
increases in leucocyte levels were recorded. Nevertheless, the puncture resultet in
highly significant decreases in levels of red blood cells, haemoglobin, packed cell
volume and total protein, albeit all post-catheterization levels stay within reference
ranges established for calves of the same age. In summary, the implementation of
ultrasonographic guidance in this method resulted in improving this technique
regarding safety, efficiency and reliablility.
90

Summary
It should certainly be stressed that catheterisation of arterial vessels is generally
accompanied by the risk of causing an embolus, thus the added value of an invasive
procedure needs to be carefully assessed. Out of 102 calves undergoing aortic
catheterisation, one case of paraplegia caused by multiple emboli in spinal vessels
leading to ischemic myelopathy is described. Despite ancillary studies (MRI),
necropsy and histological examination, the nature of the embolus remains
speculative, although the chronology of events strongly suggests a direct causal
relationship to the catheterisation process.
91

Danksagungen
An erster Stelle gilt mein Dank Herrn Prof. Dr. Jürgen Rehage für die Überlassung
dieser Arbeit, die gute Betreuung während ihrer Fertigstellung und die darüber
hinausgehende Förderung während der gesamten Dissertationszeit.
Besonders danken möchte ich Herrn Dr. Henning Meyer für die aggressiv-produktive
Zusammenarbeit, für seine Geduld und sein Glauben daran, dass trotz aller
beruflichen und privaten Rückschläge am Ende alles gut wird.
Ganz herzlich möchte ich mich bei der Harmoniebeauftragten Jessica Fischer
bedanken. Ihre unerschütterliche gute Laune, ihr Humor und ihre verlässliche
Hilfsbereitschaft machten die einjährige „Kälber-Action“ zu einem Erlebnis.
Der Konrad-Adenauer-Stiftung möchte ich für die finanzielle und ideelle Förderung
danken, die es mir ermöglicht hat, mich auf die Fertigstellung der Dissertation zu
konzentrieren und mir durch die Seminare abwechslungsreiche Einblicke in andere
interessante Themengebiete ermöglichte.
Danken möchte ich auch Frau Prof. Dr. Kästner für kompetente Hilfe bei der
Fertigstellung des Publikationsmanuskriptes.
Ein großes Dankeschön an die Assistenten der Klinik für Rinder für die
Nabeloperationen und Hilfe in Ausnahmesituationen, an die Tierpfleger für die
aufmerksame Betreuung unserer Kälber und an die Mitarbeiter des Labors für ihre
tatkräftige Unterstützung und Motivation.
Für viele unvergessliche, heitere Stunden möchte ich den „Freunden der doppelten
Sohle“, der „Tanzgruppe Nelson“ und allen anderen Mitstreitern im
Doktorandenzimmer danken. Sehr herzlich danke ich Anne List und Ilka Schulze für

ihre hervorragende Einarbeitung und tatkräftige Unterstützung, besonders in der
aufregenden Anfangszeit der Versuche.
Fabienne Ferrara danke ich besonders für ihre Unterstützung in allen Lebenslagen,
ihre konstante Freundschaft über die letzten Jahre, ihre aufmunternden Worte und
für die Sicherheit, jederzeit eine rote Couch vorfinden zu können.
Ein besonderer Dank auch an Anne Sander für die tiefgründigen Gespräche bei
Käse und Rotwein, die schöne und lustige Zeit in- und ausserhalb der Klinik, für ihre
geniale Spontanität und dafür, dass sie mir vermitteln konnte, dass man sich das
Leben auch schön machen muss.
Des Weiteren danke ich Carola und Hubert Dumann fürs Zuhören, für viel gutes
Essen und für ein wunderbares zu Hause in Hemmingen.
Der größte Dank aber gebührt meiner Familie, im Besonderen meinen Eltern, die
mich in den letzten Jahren so selbstverständlich und vertrauensvoll unterstützt
haben. Meinem Vater für sein allzeit offenes Ohr, seinen stets ehrlichen Rat und
seine Mühe, mir den Blick für die wichtigen Dinge im Leben zu schärfen. Meiner
Mutter für ihre Fürsorge und Liebe.