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.     

A clinical study on the effect in horses during medetomidine-isoflurane anaesthesia, of butorphanol constant rate infusion on isoflurane requirements, on cardiopulmonary function and on recovery characteristics

ObjectiveTo test if the addition of butorphanol by constant rate infusion (CRI) to medetomidine–isoflurane anaesthesia reduced isoflurane requirements, and influenced cardiopulmonary function and/or recovery characteristics.Study designProspective blinded randomised clinical trial.Animals61 horses undergoing elective surgery.MethodsHorses were sedated with intravenous (IV) medetomidine (7 μg kg^?1); anaesthesia was induced with IV ketamine (2.2 mg kg^?1) and diazepam (0.02 mg kg^?1) and maintained with isoflurane and a CRI of medetomidine (3.5 μg kg^?1 hour^?1). Group MB (n = 31) received butorphanol CRI (25 μg kg^?1 IV bolus then 25 μg kg^?1 hour^?1); Group M (n = 30) an equal volume of saline. Artificial ventilation maintained end-tidal CO₂ in the normal range. Horses received lactated Ringer’s solution 5 mL kg^?1 hour^?1, dobutamine <1.25 μg kg^?1 minute^?1 and colloids if required. Inspired and exhaled gases, heart rate and mean arterial blood pressure (MAP) were monitored continuously; pH and arterial blood gases were measured every 30 minutes. Recovery was timed and scored. Data were analyzed using two way repeated measures anova, independent t-tests or Mann–Whitney Rank Sum test (p < 0.05).ResultsThere was no difference between groups with respect to anaesthesia duration, end-tidal isoflurane (MB: mean 1.06 ± SD 0.11, M: 1.05 ± 0.1%), MAP (MB: 88 ± 9, M: 87 ± 7 mmHg), heart rate (MB: 33 ± 6, M: 35 ± 8 beats minute^?1), pH, PaO₂ (MB: 19.2 ± 6.6, M: 18.2 ± 6.6 kPa) or PaCO_2. Recovery times and quality did not differ between groups, but the time to extubation was significantly longer in group MB (26.9 ± 10.9 minutes) than in group M (20.4 ± 9.4 minutes).Conclusion and clinical relevanceButorphanol CRI at the dose used does not decrease isoflurane requirements in horses anaesthetised with medetomidine–isoflurane and has no influence on cardiopulmonary function or recovery.     

Comparison of hydromorphone and butorphanol for management of pain in equine patients undergoing elective arthroscopy: a randomized clinical trial

ObjectiveTo compare the effects of hydromorphone and butorphanol in horses undergoing arthroscopy and describe the pharmacokinetics of hydromorphone in anesthetized horses.Study designRandomized controlled clinical trial.AnimalsA total of 40 adult horses admitted for elective arthroscopy.MethodsHorses were randomly assigned to be administered intravenous hydromorphone (0.04 mg kg^–1; group TxH; n = 19) or butorphanol (0.02 mg kg^–1; group TxB; n = 21) prior to surgery as part of a standardized anesthetic protocol. Pain was scored by two observers unaware of group assignment using the Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) and a composite pain scale (CPS) prior to surgery (baseline), 2 hours (P2) and 4 hours (P4) following recovery from anesthesia. Blood samples were collected at various time points for determination of plasma hydromorphone concentration using liquid chromatography–tandem mass spectrometry. Data were analyzed with a mixed-effect model.ResultsMedian (range) baseline EQUUS-FAP was 1.2 (0.0–4.0) with no effect of group, time points or interaction. Baseline CPS was similar between groups. Group TxH baseline CPS was 2.5 (0.0–10.0), increased at P2 [4.5 (0–10.0); p = 0.046] and returned to baseline values at P4 [3.0 (0.0–11.0)]. Group TxB baseline CPS was 2.0 (0.0–8.0), increased at P2 [3.5 (0.0–11.0); p = 0.009] and P4 [5.0 (0.0–11.0); p < 0.001]. Pharmacokinetic terminal half-life was 774 ± 82.3 minutes, area under the curve was 1362 ± 314 ng minutes mL^–1, clearance was 30.7 ± 7.23 mL minute^–1 kg^–1 and volume of distribution at steady state was 884 ± 740 mL kg^–1.ConclusionsHydromorphone, but not butorphanol, decreased CPS back to baseline at P4 after recovery.Clinical relevanceHydromorphone may provide superior postoperative analgesia compared with butorphanol in horses undergoing arthroscopy.     

Effect of head and tail rope-assisted recovery of horses after elective and emergency surgery under general anaesthesia

The recovery phase is a critical period during equine anaesthesia. In an attempt to reduce the risk of recovery, several recovery systems, including head and tail ropes, have been developed over time. However, the clinical safety and efficacy of these systems have not been compared to a nonassisted group in a larger study. The objective of this comparative, retrospective, nonrandomised single-centre study was to determine whether the risk of developing fatal and nonfatal complications after general anaesthesia is reduced in horses assisted with head and tail ropes during recovery compared with horses recovering unassisted. Included were all horses undergoing general anaesthesia at the Large Animal Hospital, University of Copenhagen, Denmark, from 2010 to 2019. Analysed data included age, body mass, American Society of Anesthesiologists grade of physical status (ASA score), type of surgery and anaesthetic duration. Complications were divided into none, fatal and nonfatal. Logistic regression was performed to analyse the risk and predictors of fatal and nonfatal complications using the built-in R function ‘step’. Tukey’s honest significance difference test was applied to determine significance, set at P<0.05, within the categorical variables of the reduced models. The study included 1252 horses: 662 recovered with assistance (group A) and 590 without (group NA). Overall recovery-associated mortality was 1.4%: 0.6% in group A and 2.2% in group NA. Both emergency abdominal surgery (P = 0.004) and duration of surgery (P = 0.0001) affected the risk of fatal complications negatively. Assisted recovery (P = 0.02) significantly reduced the risk of fatal complications after emergency abdominal surgery. The limitation of the study was a lack of randomisation and potentially a larger proportion of sedation among assisted horses. It was concluded that emergency abdominal surgery and duration of anaesthesia are significant risk factors for fatal complications during recovery. Head and tail rope-assisted recovery is a significant factor of reducing fatal complications during recovery after emergency abdominal surgery.     

A comparison in dogs of medetomidine,with or without MK‐467, and the combination acepromazine‐butorphanol as premedication prior to anaesthesia induced by propofol and maintained with isoflurane

ObjectiveTo compare the haemodynamic effects of three premedicant regimens during propofol-induced isoflurane anaesthesia.Study designProspective, randomized cross-over study.AnimalsEight healthy purpose-bred beagles aged 4 years and weighing mean 13.6 ± SD 1.9 kg.MethodsThe dogs were instrumented whilst under isoflurane anaesthesia prior to each experiment, then allowed to recover for 60 minutes. Each dog was treated with three different premedications given intravenously (IV): medetomidine 10 μg kg^?1 (MED), medetomidine 10 μg kg^?1 with MK-467 250 μg kg^?1 (MMK), or acepromazine 0.01 mg kg^?1 with butorphanol 0.3 mg kg^?1 (AB). Anaesthesia was induced 20 minutes later with propofol and maintained with isoflurane in oxygen for 60 minutes. Heart rate (HR), cardiac output, arterial blood pressures (ABP), central venous pressure (CVP), respiratory rate, inspired oxygen fraction, rectal temperature (RT) and bispectral index (BIS) were measured and arterial and venous blood gases analyzed. Cardiac index (CI), systemic vascular resistance index (SVRI), oxygen delivery index (DO₂I), systemic oxygen consumption index (VO₂I) and oxygen extraction (EO₂) were calculated. Times to extubation, righting, sternal recumbency and walking were recorded. The differences between treatment groups were evaluated with repeated measures analysis of covariance.ResultsHR, CI, DO₂I and BIS were significantly lower with MED than with MMK. ABP, CVP, SVRI, EO₂, RT and arterial lactate were significantly higher with MED than with MMK and AB. HR and ABP were significantly higher with MMK than with AB. However, CVP, CI, SVRI, DO₂I, VO₂I, EO₂, T, BIS and blood lactate did not differ significantly between MMK and AB. The times to extubation, righting, sternal recumbency and walking were significantly shorter with MMK than with MED and AB.Conclusions and clinical relevanceMK-467 attenuates certain cardiovascular effects of medetomidine in dogs anaesthetized with isoflurane. The cardiovascular effects of MMK are very similar to those of AB.     

Tracheal trauma and pneumonia secondary to endotracheal intubation in a horse undergoing general anaesthesia,computerised tomography and myelography

Endotracheal intubation is commonly performed in horses undergoing general anaesthesia to avoid fluid aspiration and provide mechanical ventilation and inhalational anaesthetic agents. Secondary laryngeal and tracheal trauma following intubation is not rare. This case report describes the successful treatment of a horse with laryngeal and tracheal trauma secondary to intubation during myelography. Based on other clinical reports and clinical experience, movement of the endotracheal tube during myelography was considered the most likely cause of the damage. This case underscores the importance of monitoring horses for development of respiratory signs after general anaesthesia for computerised tomography and myelography.     

Sedative and analgesic effects of buprenorphine,combined with either acepromazine or dexmedetomidine,for premedication prior to elective surgery in cats and dogs

ObjectiveTo evaluate the sedative and analgesic effects of intramuscular buprenorphine with either dexmedetomidine or acepromazine, administered as premedication to cats and dogs undergoing elective surgery.Study designProspective, randomized, blinded clinical study.AnimalsForty dogs and 48 cats.MethodsAnimals were assigned to one of four groups, according to anaesthetic premedication and induction agent: buprenorphine 20 μg kg^?1 with either dexmedetomidine (dex) 250 μg m^?2 or acepromazine (acp) 0.03 mg kg^?1, followed by alfaxalone (ALF) or propofol (PRO). Meloxicam was administered preoperatively to all animals and anaesthesia was always maintained using isoflurane. Physiological measures and assessments of pain, sedation and mechanical nociceptive threshold (MNT) were made before and after premedication, intraoperatively, and for up to 24 hours after premedication. Data were analyzed with one-way, two-way and mixed between-within subjects anova, Kruskall–Wallis analyses and Chi squared tests. Results were deemed significant if p ≤ 0.05, except where multiple comparisons were performed (p ≤ 0.005).ResultsCats premedicated with dex were more sedated than cats premedicated with acp (p < 0.001) and ALF doses were lower in dex cats (1.2 ± 1.0 mg kg^?1) than acp cats (2.5 ± 1.9 mg kg^?1) (p = 0.041). There were no differences in sedation in dogs however PRO doses were lower in dex dogs (1.5 ± 0.8 mg kg^?1) compared to acp dogs (3.3 ± 1.1 mg kg^?1) (p < 0.001). There were no differences between groups with respect to pain scores or MNT for cats or dogs.ConclusionChoice of dex or acp, when given with buprenorphine, caused minor, clinically detectable, differences in various characteristics of anaesthesia, but not in the level of analgesia.Clinical relevanceA combination of buprenorphine with either acp or dex, followed by either PRO or ALF, and then isoflurane, accompanied by an NSAID, was suitable for anaesthesia in dogs and cats undergoing elective surgery. Choice of sedative agent may influence dose of anaesthetic induction agent.     

A review of the general pharmacology of ketamine and its clinical use for injectable anaesthesia in horses

Ketamine is the most commonly used injectable anaesthetic in horses. Combinations of ketamine have been used to produce short durations of anaesthesia or as total intravenous anaesthesia (TIVA) for longer diagnostic or surgical procedures. In recent years, ketamine has been used for pain management due to its effectiveness in producing analgesia at subanaesthetic doses. This paper provides a review of the pharmacological effects of ketamine in general and its clinical use for injectable anaesthesia and pain management in horses.     

A randomised,blinded, crossover study to assess the efficacy of a feed supplement in alleviating the clinical signs of headshaking in 32 horses

Reasons for performing study: Feed supplements are commonly used by owners to alleviate headshaking; however, randomised, controlled trials are required to assess their efficacy. Objective: To determine the efficacy of a feed supplement for alleviation of the clinical signs of headshaking using a randomised, blinded, placebo‐controlled trial. Methods: Using a crossover design, 44 horses previously diagnosed with chronic idiopathic headshaking received both the supplement and a matching placebo per os for 28 days with a washout period between of 14 days. Video recordings were taken at rest and exercise prior to the study and at the end of both periods of treatment. The degree of headshaking was assessed in a blinded, randomised manner by 2 veterinary surgeons. At the same time points, owners completed a questionnaire to assess the severity of headshaking signs. A Wilcoxon signed rank test was used to compare the scores while on supplement and placebo. Results: Using the video assessments, there was no significant difference between scores while on supplement compared with placebo (P = 0.7). Using the questionnaire responses, there was no significant difference between scores for any activity when the placebo and the supplement were compared with each other. However, owners reported significant improvement during all activities for both placebo and supplement compared with pretreatment scores. Conclusions and potential relevance: The supplement offered no benefit over a placebo in alleviating the clinical signs of headshaking. There appeared to be a significant proxy placebo effect when the outcome was based on subjective owner perception of clinical signs. This study demonstrated no beneficial effect of this supplement on the clinical signs of headshaking. The study did show a significant placebo effect, thereby highlighting the necessity of properly conducted, randomised controlled trials, with blinding, to assess true treatment effects in trials in animals.     

A dose titration study into the effects of diazepam or midazolam on the propofol dose requirements for induction of general anaesthesia in client owned dogs,premedicated with methadone and acepromazine

ObjectiveTo assess the effect of a benzodiazepine co–induction on propofol dose requirement for induction of anaesthesia in healthy dogs, to describe any differences between midazolam and diazepam and to determine an optimal benzodiazepine dose for co–induction.Study designProspective, randomised, blinded placebo controlled clinical trial.AnimalsNinety client owned dogs (ASA I–III, median body mass 21.5kg (IQR 10–33)) presented for anaesthesia for a variety of procedures.MethodsDogs were randomised to receive saline 0.1 mL kg^?1, midazolam or diazepam at 0.2, 0.3, 0.4 or 0.5 mg kg^?1. All dogs received 0.01 mg kg^?1 acepromazine and 0.2 mg kg^?1 methadone intravenously (IV). Fifteen minutes later, sedation was assessed and scored prior to anaesthetic induction. Propofol, 1 mg kg^?1, was administered IV, followed by the treatment drug. Further propofol was administered until endotracheal intubation was possible. Recorded data included patient signalment, sedation score, propofol dosage and any adverse reactions.ResultsMidazolam (all groups combined) significantly reduced propofol dose requirement compared to saline (p < 0.001) and diazepam (p = 0.008). Midazolam (0.4 mg kg^?1) significantly reduced propofol dose requirement (p = 0.014) compared to saline, however other doses failed to reach statistical significance. Diazepam did not significantly reduce propofol dose requirement compared to saline (p = 0.089). Dogs weighing <5 kg, regardless of treatment group, required a greater propofol dose than those weighing 5–40 kg (p = 0.002) and those >40 kg (p = 0.008). Dogs which were profoundly sedated required less propofol than those which were mildly sedated (p < 0.001) and adequately sedated (p = 0.003).Conclusions and clinical relevanceMidazolam (0.4 mg kg^?1) given IV after 1 mg kg^?1 of propofol significantly reduced the further propofol dose required for intubation compared to saline. At the investigated doses, diazepam did not have significant propofol dose sparing effects.     

A clinical trial to evaluate the effects of flumethrin or ivermectin treatment on hemoparasites, gastrointestinal parasites, conception and daily weight gain in a dairy farm in Japan

A clinical trial was performed to compare the effects of flumethrin and ivermectin treatments of grazing heifers at one farm in central Japan. 64 heifers were randomly allocated into two groups. Flumethrin (1 mg/kg pour on) was applied approximately once every 3 weeks to heifers in one group and heifers in the second group were injected approximately once every month with ivermectin (200 microg/kg; id). Between groups, no significant differences were detected in the proportions of animals that showed parasitemia of Theileria sergenti and conception risks. Significantly lower average log-transformed nematode-egg counts and higher average daily weight gain were observed in the ivermectin-treated group. Animals with higher body weight at the start of grazing and lower log-transformed total nematode-egg and coccidia-oocyst counts had higher odds of conceiving. Animals with ivermectin treatment, lower body weight at the start of grazing and lower log-transformed coccidia-oocyst count had higher daily weight gain. Ivermectin may be more useful in this farm because of the higher productivity for cattle and lower cost for its usage.