Emma J Love

Thermal and mechanical nociceptive threshold testing in horses: a review

OBJECTIVE This review evaluates the thermal and mechanical nociceptive threshold testing techniques that have been used in horses and discusses them with reference to their applications, limitations and the factors which can influence both the testing procedure itself and the animals responses. Methods to optimise the reliability and repeatability of the testing procedures are suggested and the potential clinical applications discussed. DATABASES USED Web of Science and Medline. CONCLUSIONS Thermal and mechanical nociceptive threshold testing techniques have valuable roles in both the identification of altered nociceptive function and the pre-clinical evaluation of analgesics in horses.

Effects of acepromazine, butorphanol and buprenorphine on thermal and mechanical nociceptive thresholds in horses.

REASONS FOR PERFORMING STUDY To investigate the antinociceptive effects of buprenorphine administered in combination with acepromazine in horses and to establish an effective dose for use in a clinical environment. OBJECTIVES To evaluate the responses to thermal and mechanical stimulation following administration of 3 doses of buprenorphine compared to positive (butorphanol) and negative (glucose) controls. METHODS Observer blinded, randomised, crossover design using 6 Thoroughbred geldings (3-10 years, 500-560 kg). Thermal and mechanical nociceptive thresholds were measured 3 times at 15 min intervals. Horses then received acepromazine 0.05 mg/kg bwt with one of 5 treatments i.v.: 5% glucose (Glu), butorphanol 100 µg/kg bwt (But) buprenorphine 5 µg/kg bwt (Bup5), buprenorphine 7.5 µg/kg bwt (Bup7.5) and buprenorphine 10 µg/kg bwt (Bup10). Thresholds were measured 15, 30, 45, 60, 90, 120, 150, 180, 230 min, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 24 h post treatment administration. The 95% confidence intervals for threshold temperature (ΔT) for each horse were calculated and an antinociceptive effect defined as ΔT, which was higher than the upper limit of the confidence interval. Duration of thermal antinociception was analysed using a within-subjects ANOVA and peak mechanical thresholds with a general linear model with post hoc Tukey tests. Significance was set at P<0.05. RESULTS Mean (± s.d.) durations of thermal antinociception following treatment administration were: Glu 0.5 (1.1), But 2.9 (2.0), Bup5 7.4 (2.3), Bup7.5 7.8 (2.7) and Bup10 9.4 (1.1) h. B5, B7.5 and B10 were significantly different from Glu and But. No serious adverse effects occurred, although determination of mechanical thresholds was confounded by locomotor stimulation. CONCLUSIONS Administration of acepromazine and all doses of buprenorphine produced antinociception to a thermal stimulus for significantly longer than acepromazine and either butorphanol or glucose. POTENTIAL RELEVANCE This study suggests that buprenorphine has considerable potential as an analgesic in horses and should be examined further under clinical conditions and by investigation of the pharmacokinetic/pharmacodynamic profile.

Morphine administration in horses anaesthetized for upper respiratory tract surgery

OBJECTIVE To determine the effect of morphine administration on commonly monitored cardio-respiratory variables and recovery quality in horses undergoing anaesthesia and surgery. STUDY DESIGN Prospective, randomized clinical study. ANIMALS Thirty-eight thoroughbred horses, 32 geldings and six mares, 3-13 years old, weighing 411-600 kg. MATERIALS AND METHODS A standard anaesthetic technique was used. Twenty minutes after induction of anaesthesia horses received 0.1 mg kg-1 (0.1 m) or 0.2 mg kg-1 (0.2 m) morphine by intravenous injection. A control group did not receive morphine. Heart rate, respiratory rate (fr), mean arterial pressure (MAP) and blood gases were measured before morphine administration and every 10 minutes thereafter. Horses were positioned for 35 minutes in right lateral recumbency for tension palatoplasty by cautery and were then moved into dorsal recumbency for additional intraluminal surgery comprising one or more of aryepiglottic fold resection, sub-epiglottal mucosal resection, ventriculectomy and cordectomy. A subjective recovery score from 0 (worst) to 5 (best) was assigned by a single observer who was unaware of treatment group. Two-way repeated measures anova, one-way anova, Kruskal-Wallis test, Mann-Whitney test, Pearson and Spearman correlation coefficients, and chi-squared tests were used to analyse the data where appropriate. RESULTS Arterial partial pressure of oxygen (PaO2) decreased significantly over time and was significantly lower in horses that received morphine. One horse in the control group and two horses in each of the morphine groups had a PaO2 <13 kPa. No other significant cardiopulmonary effects were detected. Recovery scores [median (range)] were higher in morphine recipients: 4 (2-5) in 0.1 m, 4 (3-5) in 0.2 m compared with 3 (2-4) in the control group. CONCLUSIONS AND CLINICAL RELEVANCE The lower PaO2 in morphine recipients did not appear to be of clinical significance in healthy horses because the number of horses with a low PaO2 was similar between groups. The quality of recovery was significantly better in morphine recipients. These results indicate that morphine may be considered for use in clinical cases although further work is required to assess the analgesic properties of the drug in this species.

Postcastration analgesia in ponies using buprenorphine hydrochloride.

Buprenorphine has recently obtained UK Marketing Authorisation for horses. The analgesic effects are long lasting, and have considerable potential for postoperative pain relief. This observer blinded, randomised study aimed to evaluate postsurgical analgesia in ponies premedicated with buprenorphine prior to castration under intravenous anaesthesia. Ponies received either 0.01 mg/kg bodyweight (BW) buprenorphine (group B) or an equivalent volume of 5 per cent glucose (group C) given intravenously before induction of anaesthesia. Pain was assessed and recorded using dynamic interactive visual analogue scores (DIVAS 0–100) and a Simple Descriptive Scale (SDS 0–3) (high scores=most pain) before and 1, 3, 6, 9, 12 and 24 hours after anaesthesia. Rescue analgesia was given if DIVAS>40 mm. Data were analysed using the Mann-Whitney U test at P<0.05. Median (range) areas under the curve for DIVAS were 63 (0–383) mm hour in group B and 209 (0–391) mm hour in group C (P=0.0348). The SDS was lower in group B than in group C (P=0.038). Three group B and five group C animals required rescue analgesia. Buprenorphine did not produce any serious adverse effects. Buprenorphine at 0.01 mg/kg BW intravenously administered before anaesthesia provided near-comprehensive postoperative analgesia after surgical castration in ponies.

Assessment of the sedative effects of buprenorphine administered with 10 μg/kg detomidine in horses

The aim of this randomised, observer-blinded, crossover study was to compare the effects of six treatments, administered intravenously to six horses: saline and saline (S/S); detomidine and saline (D/S); detomidine and 5 µg/kg buprenorphine (D/B5); detomidine and 7.5 µg/kg buprenorphine (D/B7.5); detomidine and 10 µg/kg buprenorphine (D/B10); and detomidine and 25 µg/kg butorphanol (D/BUT). The detomidine dose was 10 µg/kg for all treatments in which it was included. Sedation was subjectively assessed and recorded on a visual analogue scale. Peak sedation, duration of sedation and the area under the curve (AUC) for sedation scores were investigated using a univariate general linear model with post-hoc Tukey tests (P<0.05). Peak sedation and duration of sedation were statistically significantly different between treatments (P<0.001). No sedation was apparent after administration of S/S. The AUC was significantly different between treatments (P=0.010), with S/S being significantly different from D/S, D/BUT, D/B5 and D/B7.5, but not D/B10 (P=0.051).

Recovery characteristics following maintenance of anaesthesia with sevoflurane or isoflurane in dogs premedicated with acepromazine

A standard anaesthetic protocol was used to anaesthetise 40 dogs for intravenous urography and a retrograde urethrogram or vaginourethrogram. The dogs were allocated by blocked randomisation to receive either isoflurane or sevoflurane for maintenance of anaesthesia after they had been premedicated with acepromazine and pethidine, and anaesthesia induced with propofol. An observer who was unaware of which agent had been used assessed ataxia 30 and 60 minutes after discontinuation of administration of the anaesthetic and assigned an overall recovery score. No complications occurred during anaesthesia of either group of dogs. The scores for ataxia were significantly lower after 60 minutes than after 30 minutes, but there was no significant difference between the groups. The quality of recovery was significantly better in the dogs that received sevoflurane than in those that received isoflurane, but the recovery times were similar.

Validity and client use of information from the World Wide Web regarding veterinary anesthesia in dogs

OBJECTIVE To determine the validity of the information on the World Wide Web concerning veterinary anesthesia in dogs and to determine the methods dog owners use to obtain that information. DESIGN Web-based search and client survey. SUBJECTS 73 Web sites and 92 clients. PROCEDURES Web sites were scored on a 5-point scale for completeness and accuracy of information about veterinary anesthesia by 3 board-certified anesthesiologists. A search for anesthetic information regarding 49 specific breeds of dogs was also performed. A survey was distributed to the clients who visited the University of Georgia Veterinary Teaching Hospital during a 4-month period to solicit data about sources used by clients to obtain veterinary medical information and the manner in which information obtained from Web sites was used. RESULTS The general search identified 73 Web sites that included information on veterinary anesthesia; these sites received a mean score of 3.4 for accuracy and 2.5 for completeness. Of 178 Web sites identified through the breed-specific search, 57 (32%) indicated that a particular breed was sensitive to anesthesia. Of 83 usable, completed surveys, 72 (87%) indicated the client used the Web for veterinary medical information. Fifteen clients (18%) indicated they believed their animal was sensitive to anesthesia because of its breed. CONCLUSIONS AND CLINICAL RELEVANCE Information available on the internet regarding anesthesia in dogs is generally not complete and may be misleading with respect to risks to specific breeds. Consequently, veterinarians should appropriately educate clients regarding anesthetic risk to their particular dog.

Preliminary investigation comparing a detomidine continuous rate infusion combined with either morphine or buprenorphine for standing sedation in horses

OBJECTIVE To compare sedative and analgesic properties of buprenorphine or morphine for standing procedures combined with a detomidine continuous rate infusion (CRI). STUDY DESIGN Blinded, prospective, randomized clinical pilot study. ANIMALS Ten horses presented for dental or sinus procedures. METHODS Horses received 0.02 mg kg(-1) acepromazine intravenously (IV), followed 30 minutes later by detomidine 10 μg kg(-1) IV. Five minutes later, buprenorphine 0.01 mg kg(-1) (n = 6) or morphine 0.1 mg kg(-1) (n = 4) was administered IV. Detomidine was administered by CRI (0.2 μg kg(-1) minute(-1)) and adjusted to maintain appropriate sedation. Heart rate, respiratory frequency, gastrointestinal motility and rectal temperature were measured; pain, ataxia and sedation were scored. Sedation, pain scores and ataxia scores were analysed using a mixed linear model. Detomidine dose and procedure success scores were compared using Wilcoxons rank sum test. Complications between groups were analysed using Fishers exact test. RESULTS Two horses had incomplete data. Weights and ages were not different between groups (p = 0.15 and p = 0.42, respectively). The dose rate for detomidine was not different between groups (0.33 ± 0.02 μg kg(-1) minute(-1) in the buprenorphine group and 0.33 ± 0.05 μg kg(-1) minute(-1), in the morphine group p = 0.89). Intraoperative visual analogue scale scores were greater after buprenorphine than morphine (mean ± SD, buprenorphine 48 ± 4, morphine 40 ± 5, p = 0.0497). Procedure duration was not different between groups (buprenorphine 142 ± 33, morphine 140 ± 12 minutes). All horses treated with buprenorphine experienced complications compared with none in the morphine group (p = 0.0286). CONCLUSIONS AND CLINICAL RELEVANCE At the doses used, buprenorphine produced greater sedation but more post-operative complications than morphine. However, Type I or Type II errors cannot be excluded and larger studies are required to confirm these findings.

Comparison of two formulations of buprenorphine in cats administered by the oral transmucosal route.

This randomised, blinded, cross-over study investigated the ease of oral transmucosal administration of two formulations of buprenorphine using glucose as a control in 12 cats. The cats received three treatments: buprenorphine multi-dose, buprenorphine and the equivalent volume of glucose 5%. Ease of treatment administration, observation of swallowing, changes in pupil size, sedation, salivation, vomiting, behaviour and food intake were assessed. The data were analysed using MLwiN and multi-level modelling. Ease of administration of buprenorphine multi-dose was statistically different from glucose (P <0.001), and the administration of all treatments became easier over the study periods. Swallowing was not statistically different between groups (P >0.05). Mydriasis was evident after the administration of both formulations of buprenorphine. Sedation, salivation, vomiting, behavioural changes or in-appetence were not observed after any treatment. Cats tolerated oral transmucosal administration of glucose better than buprenorphine multi-dose, while buprenorphine administration was tolerated as well as glucose.

Practical use of opioids in cats: a state-of-the-art, evidence-based review

Rationale Recent recognition of the need to improve pain management in cats has led to the investigation of the pharmacokinetics and efficacy of opioid analgesic drugs in this species. The results of these studies may be difficult to interpret because the effect of these drugs varies with dose, route of administration and the method used to assess them. As equipotency of different opioids is not known, it is hard to compare their effects. Animals do not verbalise the pain they feel and, in cats, it may be more difficult to recognise signs of pain in comparison with other species such as dogs. Aim This article reviews the use of opioid analgesics in cats. It must be remembered that not all drugs are licensed for use in cats, and that marketing authorisations vary between different countries.