1. Clarification: The 2013 Guidelines make a distinction between euthanasia, humane killing, and slaughter, and state that neither slaughter nor humane killing is covered in the document P.68, S6.1.1. Not included among the definitions of these terms are ending the lives of healthy animals or scientific collection of animals. For clarification, whatever the term used, classification of the method, or reason given for killing animals: euthanasia, humane killing, slaughter, harvest, depopulation, scientific collection, or research-related, the Council on Accreditation’s foremost concern, in all situations, is with humane technique. The goal of humane technique is to minimize pain, distress, and the negative effect to the animal. The technique employed should result in rapid loss of consciousness followed by cardiac or respiratory arrest and, ultimately, a loss of brain function. Although complete absence of pain and distress is preferred, it is understood that it cannot always be achieved P7.13.2.

https://works.bepress.com/cheryl_greenacre/14/download/

AVMA Guidelines for the Euthanasia of Animals: 2013 Edition

Many are frustrated with the lack of translational progress in the pain field, in which huge gains in basic science knowledge obtained using animal models have not led to the development of many new clinically effective compounds. A careful re-examination of animal models of pain is therefore warranted. Pain researchers now have at their disposal a much wider range of mutant animals to study, assays that more closely resemble clinical pain states, and dependent measures beyond simple reflexive withdrawal. However, the complexity of the phenomenon of pain has made it difficult to assess the true value of these advances. In addition, pain studies are importantly affected by a wide range of modulatory factors, including sex, genotype and social communication, all of which must be taken into account when using an animal model.

Animal models of pain: progress and challenges

Ketamine, a racemic mixture consisting of (S)- and (R)-ketamine, has been in clinical use since 1970. Although best characterized for its dissociative anesthetic properties, ketamine also exerts analgesic, anti-inflammatory, and antidepressant actions. We provide a comprehensive review of these therapeutic uses, emphasizing drug dose, route of administration, and the time course of these effects. Dissociative, psychotomimetic, cognitive, and peripheral side effects associated with short-term or prolonged exposure, as well as recreational ketamine use, are also discussed. We further describe ketamine’s pharmacokinetics, including its rapid and extensive metabolism to norketamine, dehydronorketamine, hydroxyketamine, and hydroxynorketamine (HNK) metabolites. Whereas the anesthetic and analgesic properties of ketamine are generally attributed to direct ketamine-induced inhibition of N-methyl-D-aspartate receptors, other putative lower-affinity pharmacological targets of ketamine include, but are not limited to, γ-amynobutyric acid (GABA), dopamine, serotonin, sigma, opioid, and cholinergic receptors, as well as voltage-gated sodium and hyperpolarization-activated cyclic nucleotide-gated channels. We examine the evidence supporting the relevance of these targets of ketamine and its metabolites to the clinical effects of the drug. Ketamine metabolites may have broader clinical relevance than was previously considered, given that HNK metabolites have antidepressant efficacy in preclinical studies. Overall, pharmacological target deconvolution of ketamine and its metabolites will provide insight critical to the development of new pharmacotherapies that possess the desirable clinical effects of ketamine, but limit undesirable side effects.

https://pharmrev.aspetjournals.org/content/pharmrev/70/3/621.full.pdf

Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms

Physiology of Behavior

Working party: Mrs Bryony Close (Chair), Dr Keith Banister, Dr Vera Baumans, Dr Eva-Maria Bernoth, Dr Niall Bromage, Dr John Bunyan, Professor DrWolff Erhardt, Professor Paul Flecknell, Dr Neville Gregory, Professor Dr Hansjoachim Hackbarth, Professor David Morton & M r Clifford Warwick Correspondence to: Mrs BClose, Battleborough Croft, Battleborough Lane, Brent Knoll, Highbridge, SomersetTA9 4DS, UK

https://lan.sagepub.com/content/31/1/1.full.pdf+html

Recommendations for euthanasia of experimental animals: Part 2

Medetomidine and dexmedetomidine: a review of cardiovascular effects and antinociceptive properties in the dog.

The Glasgow Composite Measure Pain Scale was developed to measure acute pain in dogs in a hospital setting. In this investigation a modified version of the scale was applied in a centre with a different surgical case load and analgesic protocols, and where English is not the first language, to test its validity in a different clinical environment. The modified scale was used to score pain in 60 dogs during the 24 hours after surgery. Their levels of sedation and a clinical impression of their pain were scored at the same time. Three questions were considered; first, how the modified pain score was related to the pain assessed subjectively, secondly, how it related to variables such as the surgical procedure and the dog's health and thirdly, how it changed over time. The mean modified pain scores for the dogs rated subjectively as having no, mild, moderate or severe pain were significantly different, indicating that the modified scale distinguished between pain of different severities. The changes in the dogs' scores also followed the expected changes in their level of pain with time, providing empirical evidence that the scale measures pain.

Application of a modified form of the Glasgow pain scale in a veterinary teaching centre in the Netherlands

Physiological parameters, metabolic parameters and stress-related hormones are evaluated in horses anaesthetized with isoflurane in oxygen combined with lidocaine intravenously. Two groups of horses anaesthetized with isoflurane (six horses in each group) were studied: a lidocaine group (IL), which received intravenous lidocaine and a control group (C), which received intravenous saline. Horses in both groups were premedicated with detomidine (i.v.), and anaesthesia was induced with midazolam-ketamine (i.v.). The lidocaine group received intravenous lidocaine as a loading dose of 2.5 mg kg(-1) at 15 min after induction of anaesthesia directly followed by a maintenance dosage of 50 microg kg(-1) min(-1), while the control group received saline (i.v.) following the same regime. End-tidal isoflurane and standard physiological parameters were measured. Blood was sampled for measurement of lidocaine, stress hormones and metabolic parameters. The end-tidal isoflurane concentration in the lidocaine group was 0.96 +/- 0.06% versus 1.28 +/- 0.06% (mean +/- SD) in the control group, a significant (P < 0.05) reduction of 25%. No significant differences were found regarding stress-related hormones, metabolic and physiological parameters. This study suggests that the use of lidocaine to decrease the concentration of isoflurane to obtain a sufficient surgical anaesthesia has no subsequent effects on physiological and metabolic parameters or stress-related hormones.

Effects of intravenous lidocaine on isoflurane concentration, physiological parameters, metabolic parameters and stress-related hormones in horses undergoing surgery.

Ludo J. Hellebrekers

Papers

Medetomidine and dexmedetomidine: a review of cardiovascular effects and antinociceptive properties in the dog.

Application of a modified form of the Glasgow pain scale in a veterinary teaching centre in the Netherlands

Effects of intravenous lidocaine on isoflurane concentration, physiological parameters, metabolic parameters and stress-related hormones in horses undergoing surgery.

Dexmedetomidine continuous rate infusion during isoflurane anaesthesia in canine surgical patients.

Application of a Composite Pain Scale to Objectively Monitor Horses with Somatic and Visceral Pain under Hospital Conditions