Preanesthesia, Anesthesia, Analgesia, and Euthanasia Paul Flecknell, MA, Vetmb, Phd, DECLAM, DLAS, DECVA, (Hon) DACLAM, (Hon) Frcvsa, Jennifer L.S
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CHAPTER 24 Preanesthesia, Anesthesia, Analgesia, and Euthanasia Paul Flecknell, MA, VetMB, PhD, DECLAM, DLAS, DECVA, (Hon) DACLAM, (Hon) FRCVSa, Jennifer L.S. Lofgren, DVM, MS, DACLAMb, Melissa C. Dyson, DVM, DACLAMb, Robert R. Marini, DVMc, M. Michael Swindle, DVMd and Ronald P. Wilson, VMD, MSe aComparative Biology Medicine, Newcastle University, Newcastle Upon Tyne, UK bUnit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA cDivision of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts dDepartment of Comparative Medicine, Medical University of South Carolina, Charleston, SC, USA ePenn State College of Medicine, Department of Comparative Medicine, Hershey, PA, USA OUTLINE I. Introduction 1136 IV. Ferrets 1156 A. Introduction 1156 II. Rodents 1136 B. Preoperative Assessment and Preparation 1157 A. Introduction 1136 C. Intraoperative Anesthetics 1158 B. Preoperative Assessment and Preparation 1136 D. Intraoperative Monitoring and Support 1160 C. Anesthetic Agents 1137 E. Postoperative Recovery 1160 D. Intraoperative Monitoring and Support 1143 F. Acute and Chronic Analgesic Therapy 1160 E. Special Anesthetic Considerations 1144 G. Special Anesthetic Considerations 1161 F. Analgesic Therapy 1145 G. Species Considerations 1147 V. Swine 1162 H. Euthanasia 1148 A. Introduction 1162 B. Preoperative Assessment and Preparation 1162 III. Rabbits 1149 C. Intraoperative Anesthesia 1163 A. Introduction 1149 D. Intraoperative Monitoring and Support 1166 B. Preoperative Assessment and Preparation 1149 E. Special Anesthetic Considerations 1166 C. Intraoperative Anesthesia 1150 F. Postoperative Recovery 1167 D. Intraoperative Monitoring and Support 1154 G. Acute and Chronic Analgesic Therapy 1167 E. Special Anesthetic Considerations 1154 H. Euthanasia 1168 F. Acute and Chronic Analgesic Therapy 1155 Laboratory Animal Medicine, Third Edition DOI: http://dx.doi.org/10.1016/B978-0-12-409527-4.00024-9 1135 © 20122015 Elsevier Inc. All rights reserved. 1136 24. PREANESTHESIA, ANESTHESIA, ANALGESIA, AND EUTHANASIA VI. Small Ruminants 1168 C. Intraoperative Anesthesia 1182 A. Introduction 1168 D. Intraoperative Monitoring and Support 1184 B. Preoperative Evaluation and Preparation 1169 E. Special Anesthesia Considerations 1185 C. Postoperative Recovery and Pain Management 1178 F. Postoperative Recovery 1186 D. Euthanasia 1180 G. Euthanasia 1187 VII. Nonhuman Primates 1180 References 1187 A. Introduction 1180 B. Preoperative Assessment and Preparation 1180 I. INTRODUCTION analgesia for rodents are rapidly evolving. The reader is urged to consult laboratory animal anesthesia texts The purpose of this chapter is to provide practical (Gaertner et al., 2008; Flecknell, 2009) and journals for advice for administering anesthetics, analgesics, and more complete and timely information. euthanasia agents to the most commonly used labora- tory animal species. It is not meant to be an exhaustive review of all anesthetic and analgesic protocols used in B. Preoperative Assessment and Preparation these species. More detailed information is available in 1. Preanesthetic Evaluation both specialist laboratory animal anesthesia texts, (e.g., No anesthetic regimen is universally safe or appro- Fish, 2008; Kohn et al., 1997; Flecknell, 2009), and general priate. Anesthetic protocols that are satisfactory for veterinary anesthesia texts (e.g., Tranquilli et al., 2007). healthy animals can severely compromise or be fatal The most commonly used rodent species, rabbits, to unhealthy ones. A vigilant rodent health surveil- ferrets, pigs, small ruminants, and nonhuman primates lance program is the first line of defense but cannot be were selected for inclusion in this chapter. These species expected to detect alterations in husbandry or experi- encompass the overwhelming majority of laboratory ani- mental manipulations that may affect anesthesia out- mals that are currently utilized. References for in-depth comes. Preanesthetic considerations should include an discussion of anesthetic and analgesic protocols for each assessment of appearance, behavior, and bodyweight species are included within its particular section. for evidence of abnormality as well as for establishing doses for injectable agents. The history of the group of II. RODENTS animals should be examined to identify experimental, housing, and strain-specific features that might affect A. Introduction choice of anesthesic agents and techniques. In addi- tion, sex, age, and specific procedures may be expected Rodents, especially rats and mice, are the most to alter the effects of anesthesia, often to a surprising numerous and arguably the most important group of degree. A summary of anesthetic and analgesic varia- animals used in research. Among the factors that dif- tions among mice and rat stocks and strains is available ferentiate anesthetic techniques used in rodents from in the chapter on Laboratory Rodents in the second edi- those more commonly employed in larger species are tion of the text Anesthesia and Analgesia in Laboratory the small size of the animals, the perceived and often Animals (Gaertner et al., 2008). Unless the anesthetic real difficulties of vascular and airway access, and the regimen is known to be safe and effective in the animals frequent need to anesthetize large numbers of animals to be used, a pilot study should be conducted to assess in a relatively short time. Trends that have combined and verify the effects of the proposed anesthetic and to increase attention on the safe and appropriate anes- analgesic protocol (Flecknell, 2009). In all cases, it is thetic and analgesic delivery and monitoring for rodents important to allow adequate time for newly arrived ani- include: humane concerns; scientific recognition of the mals to become acclimated to changes in housing, diet, effects of pain, anesthesia, and analgesia on experimen- and husbandry conditions and to recover from shipping tal design; and the expense of generation or purchase stress. An acclimation period of at least 24–72 h is rec- of genetically altered rodents. This section will briefly ommended for rodents (Capdevila et al., 2007; Obernier discuss common anesthetic techniques for mice and rats, and Baldwin, 2006). Fasting is not usually necessary or with comments on hamsters, gerbils, and guinea pigs. recommended before anesthesia and surgery in rodents Drugs, techniques, and approaches to anesthesia and (Gaertner et al., 2008). LABORATORY ANIMAL MEDICINE II. RODENTS 1137 2. Choice of Anesthetic Techniques TABLE 24.1 Selected Anesthetic and Analgesic Doses for Micea All anesthetics have undesirable properties, so a pri- Drug Dose Route Duration mary goal must be to select an anesthetic technique that has the least adverse effect on the animal and on the ANESTHESTICS research. Thus, the goals of the research and the limita- Barbiturates tions this places on selection of the anesthetic agents must Pentobarbital 40–50 mg/kg IP 20–40 min be taken into account in formulating an anesthetic pro- tocol. For example, when prolonged stable anesthesia is EMTU (inactin) 80–mg/kg IP 60–240 min required, the choice might favor an inhalation or continu- Dissociative agents and combinations ous infusion method to avoid the variations that tend to occur with repeated bolus administration of drugs. A pro- Ketamine+ 100 mg/kg IP 20–30 min longed recovery period can further stress the animal and acepromazine 5 mg/kg the resources of the facility, favoring selection of agents Ketamine+ 50–75 mg/kg IP 20–30 min that have rapid recovery characteristics or agents that can medetomidine 1–10 mg/kg easily be reversed, such as α2-agonists, benzodiazepines, and some opioids. Finally, some techniques that meet all Ketamine+ 80–100 mg/kg IP 20–30 min of the preceding criteria may be too technically demand- xylazine 5–10 mg/kg ing or simply too expensive for the proposed research. Ketamine+ 80–100 mg/kg IP 30–40 min Inhalation anesthesia with modern agents requires the Xylazine+ 5–10 mg/kg proper equipment and training. Precise intravenous infu- sion methods may require an infusion pump, as well as acepromazine 3 mg/kg vascular access and experience with the technique. In Neuroleptanesthetics many cases, only brief anesthesia may be needed, such as procedures that may not be extremely painful but require Fentanyl-fluanisone (hypnorm) adequate restraint for the safety of the animal and the b operator (e.g., bleeding, injections, or sampling of small +midazolam 10.0 ml/kg IP 30–40 min amounts of tissue). Brief exposure to an inhalation agent Fentanyl-fluanisone 0.4 ml/kg is often selected to meet these needs. (hypnorm) In summary, selection of a suitable anesthetic tech- +diazepam 5 mg/kg IP 30–40 min nique must include professional and humane consid- Inhalant agents erations, scientific requirements and restrictions, and recognition of technical and personnel limitations. Isoflurane 1–4%, to effect Inhalant 3. Preanesthetic Medications Other agents Preanesthetic drugs are not commonly used in Propofol 12–26 mg/kg IV 5–10 min rodents. However, the advantages of sedation, analge- Tribromoethanol 125–300 mg/kg IP 15–45 min sia, and reduced doses of the general anesthetic agent or agents apply equally well to rodents. The principal ANALGESICS disadvantage of using a preanesthetic agent in rodents Buprenorphine 0.05–0.1 mg/kg SC, IP 6–12 h is the need to restrain and thus stress the animals twice Butorphanol 1–5 mg/kg SC, IP 4 h rather than once for the induction of anesthesia.