Grimace Scores: Tools to Support the Identification of Pain in Mammals Used in Research

The 3Rs, Replacement, Reduction and Refinement, is a framework to ensure the ethical and justified use of animals in research. The implementation of refinements is required to alleviate and minimise the pain and suffering of animals in research. Public acceptability of animal use in research is contingent on satisfying ethical and legal obligations to provide pain relief along with humane endpoints. To fulfil this obligation, staff, researchers, veterinarians, and technicians must rapidly, accurately, efficiently and consistently identify, assess and act on signs of pain. This ability is paramount to uphold animal welfare, prevent undue suffering and mitigate possible negative impacts on research. Identification of pain may be based on indicators such as physiological, behavioural, or physical ones. Each has been used to develop different pain scoring systems with potential benefits and limitations in identifying and assessing pain. Grimace scores are a promising adjunctive behavioural technique in some mammalian species to identify and assess pain in research animals. The use of this method can be beneficial to animal welfare and research outcomes by identifying animals that may require alleviation of pain or humane intervention. This paper highlights the benefits, caveats, and potential applications of grimace scales

Accidental alfaxalone overdose in a mature cat undergoing anaesthesia for magnetic resonance imaging.

Case summary This case report describes the clinical signs and treatment of an alfaxalone 10 times overdose in a 12-year-old cat undergoing anaesthesia for MRI. The cat was discharged from hospital following a prolonged recovery including obtunded mentation and cardiorespiratory depression for several hours following cessation of anaesthesia. The cat received supportive therapy that included supplemental oxygen via a face mask, intravenous crystalloid fluids and active rewarming. The benefits of using alfaxalone for maintenance of anaesthesia, its pharmacokinetics and previously reported lethal doses are discussed. Strategies for reducing the incidence of medication errors are presented. Relevance and novel information An unintentional overdose of alfaxalone by continuous rate infusion has not been reported previously in a cat. Treatment is supportive and directed towards maintenance of the cardiorespiratory systems. Whenever possible, smart pumps that have been designed to reduce human error should be used to help prevent medication errors associated with continuous rate infusions

Observations on the use of a pain numbing device for repetitive percutaneous sampling in sheep

Aims: To evaluate the success of a commercially available analgesic device (CoolSense; Coolsense Ltd, Tel Aviv, Israel) in ameliorating pain while sampling from subcutaneous tissue cages in sheep. Methods: The CoolSense device was used as part of a major parent study involving repetitive percutaneous sampling of subcutaneous tissue cages in seven sheep. Sampling was performed by passing a hypodermic needle through the skin and withdrawing fluid from the tissue cage. Each sheep had 10 tissue cages that were individually sampled 14 times over 74 h. The device was placed on the skin of the sampling site immediately before sampling cooling and numbing the skin. The reaction of the sheep was observed by the operators, flinching or jumping as the needle was passed through the skin was deemed to be a failure. We recorded the success or failure of the device for each needle stick. This was opportunistic data collection as part of a pharmacokinetic trial, therefore no controls were included. Results: A total of 1655 observations were recorded and then analysed using a generalised linear mixed model. Overall, 1380 of 1655 (83.4%) observations were recorded as successfully providing analgesia. Marked inter-occasion variability was noted with success ranging from 61.42% to 92.86% across sheep:period (approximately 140 observations each). As no controls were available, the effect of treatment could not be evaluated. Conclusions and clinical relevance: The CoolSense device is a viable option for veterinary research and clinical applications

Influence of two administration rates of alfaxalone at induction on its relative potency in cats: a pilot study

Objectives The aim of the study was to evaluate, in a controlled, randomised, masked clinical trial, the influence of administration rate of alfaxalone at induction on its relative potency in cats and to report the incidence of cardiorespiratory adverse effects. Methods Twelve healthy female domestic cats admitted for ovariohysterectomy were premedicated with buprenorphine 20 µg/kg intramuscularly and alfaxalone 3.0 mg/kg subcutaneously. Sedation scores were established (using a published scale ranging from 1 [no sedation] to 5 [profound sedation]) prior to anaesthesia induction with alfaxalone intravenously at 2 mg/kg/min (group A2; n = 6) or 0.5 mg/kg/min (group A0.5; n = 6) to effect until orotracheal intubation was achieved. Sedation scores and alfaxalone induction doses were compared between the groups, using a Mann-Whitney exact test. Results are reported as median and range. Presence of apnoea (no breathing for more than 30 s) or hypotension (mean arterial blood pressure <60 mmHg) within 5 mins postintubation was also reported. Results Although sedation scores (1.5 [range 1.0-3.0] and 2.5 [range 1.0-3.0] for A2 and A0.5, respectively) were not significantly different ( P = 0.32), cats in group A2 required significantly more alfaxalone (4.3 mg/kg [range 3.4-7.0 mg/kg]) than group A0.5 (2.1 mg/kg [range 1.5-2.5 mg/kg]) ( P = 0.002). Two cats in each group presented postinduction apnoea, and two cats in group A2 and three cats in group A0.5 presented postinduction hypotension. Conclusions and relevance The use of a slower induction infusion rate resulted in an increase in the alfaxalone relative potency without obvious cardiorespiratory benefit

The use of alfaxalone and remifentanil total intravenous anesthesia in a dog undergoing a craniectomy for tumor resection

A 7-year-old castrated border collie dog was anesthetised for surgical resection of a hippocampal mass. Anesthesia was maintained using a previously unreported TIVA protocol for craniectomy consisting of alfaxalone and remifentanil. Recovery was uneventful, and the patient was discharged from hospital. We describe the anesthetic management of this case

Clinical evaluation of alfaxalone to induce and maintain anaesthesia in cats undergoing neutering procedures

This study looked at the use and efficacy of alfaxalone for total intravenous anaesthesia (TIVA) in cats. Following intramuscular medetomidine (20 μg/kg) and morphine (0.3 mg/kg) premedication, anaesthesia was induced and maintained with intravenous alfaxalone. Patients were breathing 100% oxygen. Heart rate (HR), respiratory rate (RR), end-tidal carbon dioxide, oxygen saturation of haemoglobin and indirect arterial blood pressure via Doppler (DAP) were recorded every 5 mins. Thirty-four cats (10 males and 24 females), between the age of 6 and 18 months, and weighing between 1.8 and 5.3 kg, and undergoing neutering procedures were included in this study. The results are presented as median (min, max) values. The time to first spontaneous movement (TS) was >30 mins in 19 cats, of which 12 received atipamezole for reversal of the effects of medetomidine. The TS was 53 (43, 130) mins in these 12 cats and 50 (40, 72) mins in the other seven cats. The body temperature in those 19 cats was significantly lower than the other cats (P = 0.05). The alfaxalone induction dose and maintenance infusion rate were1.7 (0.7, 3.0) mg/kg and 0.18 (0.06, 0.25) mg/kg/min, respectively. The HR, RR and DAP were 145 (68, 235) beats/min, 17 (5, 40) breaths/min and 110 (58, 210) mmHg, respectively. Apnoea was not observed in any cat. In conclusion, alfaxalone TIVA in combination with medetomidine and morphine premedication was effective in feral and domestic cats for the performance of neutering surgery; low body temperature might have resulted in longer recoveries in some cats

A review of the pharmacology and clinical application of alfaxalone in cats

Alfaxalone-2-hydroxpropyl-β-cyclodextrin (alfaxalone-HPCD) was first marketed for veterinary use in Australia in 2001 and has since progressively became available throughout the world, including the USA, where in 2012 Food and Drug Administration (FDA) registration was granted. Despite the growing body of published works and increasing global availability of alfaxalone-HPCD, the accumulating evidence for its use in cats has not been thoroughly reviewed. The purpose of this review is: (1) to detail the pharmacokinetic properties of alfaxalone-HPCD in cats; (2) to assess the pharmacodynamic properties of alfaxalone-HPCD, including its cardiovascular, respiratory, central nervous system, neuromuscular, hepatic, renal, haematological, blood-biochemical, analgesic and endocrine effects; and (3) to consider the clinical application of alfaxalone-HPCD for sedation, induction and maintenance of anaesthesia in cats. Based on the published literature, alfaxalone-HPCD provides a good alternative to the existing intravenous anaesthetic options for healthy cats