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Love E.J.,University of Bristol | Pelligand L.,The Royal Veterinary College | Taylor P.M.,Taylor Monroe | Murrell J.C.,University of Bristol | Sear J.W.,University of Oxford
Veterinary Anaesthesia and Analgesia | Year: 2015

Objective: Describe the pharmacokinetics of buprenorphine and norbuprenorphine in horses and to relate the plasma buprenorphine concentration to the pharmacodynamic effects. Study design: Single phase non-blinded study. Animals: Six dedicated research horses, aged 3-10 years and weighing 480-515 kg. Methods: Thermal and mechanical nociceptive thresholds, heart and respiratory rates and locomotor activity were measured before and 15, 30, 45 & 60 minutes and 2, 4, 6, 8, 12 & 24 hours post-administration of 10 μg kg-1 buprenorphine IV. Intestinal motility was measured 1, 6, 12 & 24 hours after buprenorphine administration. Venous blood samples were obtained before administration of buprenorphine 10 μg kg-1 IV and 1, 2, 4, 6, 10, 15, 30, 45 & 60 minutes, and 2, 4, 6, 8, 12 & 24 hours afterwards. Plasma buprenorphine and norbuprenorphine concentrations were measured using a liquid chromatography-tandem mass spectroscopy (LC-MS/MS) assay with solid-phase extraction. A non-compartmental method was used for analysis of the plasma concentration-time data and plasma buprenorphine concentrations were modelled against two dynamic effects (change in thermal threshold and mechanical threshold) using a simple Emax model. Results: Plasma buprenorphine concentrations were detectable to 480 minutes in all horses and to 720 minutes in two out of six horses. Norbuprenorphine was not detected. Thermal thresholds increased from 15 minutes post-buprenorphine administration until the 8-12 hour time points. The increase in mechanical threshold ranged from 3.5 to 6.0 Newtons (median: 4.4 N); and was associated with plasma buprenorphine concentrations in the range 0.34-2.45 ng mL-1. Conclusions and clinical relevance: The suitability of the use of buprenorphine for peri-operative analgesia in the horse is supported by the present study. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia. Source

de Vries A.,Animal Health Trust | Taylor P.M.,Taylor Monroe
Veterinary Anaesthesia and Analgesia | Year: 2015

Objective: To compare intravenous (IV) midazolam and diazepam administered with ketamine for induction of anaesthesia in ponies, already sedated with detomidine, undergoing field castration. Study design: Prospective, randomised, 'blinded', clinical study. Animals: Twenty Welsh pony yearlings. Methods: After IV injection of detomidine (20 μg kg-1) and phenylbutazone (4.4 mg kg-1) ponies were allocated to receive either IV midazolam (group M) or diazepam (group D) (both 0.06 mg kg-1) with ketamine (2.2 mg kg-1) for induction of anaesthesia. Using simple descriptive scales, quality of sedation, induction, endotracheal intubation, surgical conditions and recovery were scored by observers blinded to treatment. Time from sedation to induction of anaesthesia, IV injection to lateral recumbency, induction to start of surgery, induction to first head lift and to standing, and total surgical time were measured. Cardiorespiratory function was assessed every 5 minutes. Time, number and total quantity of additional IV ketamine as well as any adverse effects were documented. Data were tested for normality and analysed using two-way anova with Bonferroni post hoc tests, unpaired t-tests and Mann-Whitney U tests as appropriate. Significance was set at p < 0.05. Results: There were no significant group differences in any of the measured variables except bodyweight (mean ± SD: group M 163 ± 12 kg; group D 150 ± 7 kg; p = 0.01). One pony in group M required ketamine 15 minutes after induction of anaesthesia. Surgical conditions were good in all cases; time from induction to standing was 50 ± 11 minutes in group M and 48 ± 12 minutes in group D. There were no adverse effects. Recoveries were uneventful with minimal ataxia. Conclusions and clinical relevance: Midazolam and diazepam at 0.06 mg kg-1 can be used interchangeably in combination with ketamine for IV induction of short term anaesthesia in ponies. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia. Source

Luna S.P.L.,Paulista University | Lopes C.,Paulista University | Rosa A.C.,Paulista University | Oliveira F.A.,Paulista University | And 3 more authors.
Equine Veterinary Journal | Year: 2015

Reasons for performing study: To validate a model for investigating the effects of analgesic drugs on mechanical, thermal and electrical stimulation testing. Objectives: To investigate repeatability, sensitivity and specificity of nociceptive tests. Study design: Randomised experiment with 2 observers in 2 phases. Methods: Mechanical (M), thermal (TL) and electrical (E) stimuli were applied to the dorsal metacarpus (M-left and TL-right) and coronary band of the left thoracic limb (E) and a thoracic thermal stimulus (TT) was applied caudal to the withers in 8 horses (405 ± 43kg). Stimuli intensities were increased until a clear avoidance response was detected without exceeding 20N (M), 60°C (TL and TT) and 15V (E). For each set of tests, 3 real stimuli and one sham stimulus were applied (32 per animal) using a blinded, randomised, crossover design repeated after 6 months. A distribution frequency and, for each stimulus, Chi-square and McNemar tests compared both the proportion of positive responses detected by 2 observers and the 2 study phases. The κ coefficients estimated interobserver agreement in determining endpoints. Sensitivity (384 tests) and specificity (128 tests) were evaluated for each nociceptive stimulus to assess the evaluators' accuracy in detecting real and sham stimuli. Results: Nociceptive thresholds were 3.1 ± 2N (M), 8.1 ± 3.8V (E), 51.4 ± 5.5°C (TL) and 55.2 ± 5.3°C (TT). The level of agreement after all tests, M, E, TL and TT, was 90, 100, 84, 98 and 75%, respectively. Sensitivity was 89, 100, 89, 98 and 70% and specificity 92, 97, 88, 91 and 94%, respectively. Conclusions: The high interobserver agreement, sensitivity and specificity suggest that M, E and TL tests are valid for pain studies in horses and are suitable tools for investigating antinociceptive effects of analgesics in horses. © 2015 EVJ Ltd. Source

Slingsby L.S.,University of Bristol | Murrell J.C.,University of Bristol | Taylor P.M.,Taylor Monroe
Veterinary Journal | Year: 2012

Naloxone can enhance the antinociceptive/analgesic effects of buprenorphine in humans and rats. The antinociceptive effects of a patented 15:1 buprenorphine:naloxone combination was investigated in cats using a thermal and mechanical nociceptive model. Twelve cats received buprenorphine 10 μg/kg, naloxone 0.67 μg/kg or a buprenorphine-naloxone combination intramuscularly in a randomised cross over study. Using thermal and mechanical analgesiometry validated in the cat, pre-treatment baselines were measured. Following test drug administration, thresholds were studied for the next 24 h. Naloxone did not enhance the thermal antinociceptive effect of buprenorphine. The results from this study are in agreement with previously published work showing that naloxone antagonises the effects of clinically analgesic doses of buprenorphine. Mechanical nociceptive thresholds were not affected by buprenorphine. © 2011 Elsevier Ltd. Source

Bouts T.,Zoological Society London | Karunaratna D.,UK Institute of Zoology | Berry K.,Zoological Society London | Dodds J.,Zoological Society London | And 3 more authors.
Journal of Zoo and Wildlife Medicine | Year: 2011

Twenty-six adult semifree-ranging Bennett's wallabies were anesthetized. Animals in group MA received medetomidine 0.1 mg/kg and alfaxalone 4 mg/kg i.m. in a 5-ml dart, whereas those in group MK received medetomidine 0.1 mg/kg and ketamine 5 mg/kg i.m. in a 3-ml dart. Dosages were based on estimated body weights. The wallabies were allowed to recover spontaneously or, if still nonresponsive at the end of the procedure, were given atipamezole 0.5 mg/kg (half the dose via i.m. and the other half via i.v.). Heart rate and respiratory rate were monitored at 5-min intervals, temperature at 10-min intervals, and two arterial blood samples were taken for blood gas analysis. Statistical analysis was performed by using analysis of variance (P < 0.05). The use of 5-ml darts in group MA compared with 3-ml darts in group MK could potentially increase the risk of iatrogenic trauma and should be considered. Induction and maintenance of anesthesia were satisfactory in both groups. There were no significant differences between the groups in mean time to first effect, recumbency, and approach, or to time to sternal recumbency and standing after reversal with atipamezole. Although bradycardia was present in both groups, no statistical differences were calculated for respiratory rate and heart rate, whereas the mean cloacal temperature was significantly lower in group MA (P = 0.01). Mixed acid-base disturbances occurred in both groups. All but one animal in group MK needed atipamezole at the end of the procedure. No adverse effects were observed after recovery. Copyright 2011 by American Association of Zoo Veterinarians. Source

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