Influence of detomidine and buprenorphine on motor-evoked potentials in horses

Horses need to be sedated before they are investigated by transcranial magnetic stimulation because of the mild discomfort induced by the evoked muscle contraction and the noise of stimulation. This paper describes the influence of a combination of detomidine (10 microg/kg bodyweight) and a low dose of buprenorphine (2.4 microg/kg) on the onset latency and peak-to-peak amplitude of magnetic motor-evoked potentials in normal horses. There were no significant differences between measurements of these parameters made before the horses were sedated and measurements made 10 and 30 minutes after the drugs were administered.     

A comparison of epidural buprenorphine plus detomidine with morphine plus detomidine in horses undergoing bilateral stifle arthroscopy

ObjectiveTo compare the analgesic efficacy of buprenorphine plus detomidine with that of morphine plus detomidine when administered epidurally in horses undergoing bilateral stifle arthroscopy.Study designProspective, randomized, blinded clinical trial.AnimalsTwelve healthy adult horses participating in an orthopedic research study. Group M (n = 6) received morphine (0.2 mg kg^?1) and detomidine (0.15 mg kg^?1) epidurally; group B (n = 6) received buprenorphine (0.005 mg kg^?1) and detomidine (0.15 mg kg^?1) epidurally.MethodsHorses received one of two epidural treatments following induction of general anesthesia for bilateral stifle arthroscopy. Heart rate (HR), mean arterial blood pressure (MAP), end-tidal CO₂ (Pe’CO₂), and end-tidal isoflurane concentrations (E’Iso%) were recorded every 15 minutes following epidural administration. Post-operative assessment was performed at 1, 2, 3, 6, 9, 12, and 24 hours after standing; variables recorded included HR, respiratory rate (f_R), abdominal borborygmi, defecation, and the presence of undesirable side effects. At the same times post-operatively, each horse was videotaped at a walk and subsequently assigned a lameness score (0-4) by three ACVS diplomates blinded to treatment and who followed previously published guidelines. Nonparametric data were analyzed using Wilcoxon’s rank-sum test. Inter- and intra-rater agreement were determined using weighted kappa coefficients. Statistical significance was set at p = 0.05.ResultsNo statistically significant differences were found between groups with respect to intra-operative HR, MAP, E’Iso%, or post-operative HR, gastrointestinal function and cumulative median lameness scores. Post-operative f_R in group B [24 (12-30), median (range)] breaths per minute was significantly higher than in group M [18 (15-20)] breaths per minute, p = 0.04.Conclusions and clinical relevanceIn horses undergoing bilateral stifle arthroscopy, these doses of buprenorphine plus detomidine injected epidurally produced analgesia similar in intensity and duration to that of morphine plus detomidine injected epidurally.     

Cardiopulmonary effects of buprenorphine in horses

OBJECTIVE: To investigate the effects of buprenorphine on cardiopulmonary variables and on abdominal auscultation scores in horses. ANIMALS: 6 healthy adult horses. PROCEDURES: Horses were restrained in stocks and allocated to 2 treatments in a randomized crossover design, with 1-week intervals between each treatment. Saline (0.9% NaCl) solution was administered IV as a control, whereas buprenorphine (10 mug/kg, IV) was administered to the experimental group. Cardiopulmonary data were collected for 120 minutes after buprenorphine or saline solution administration. Abdominal auscultation scores were monitored for 2 and 12 hours after drug administration in the control and experimental groups, respectively. RESULTS: Following control treatment, horses remained calm while restrained in the stocks and no significant changes in cardiopulmonary variables were observed throughout the study. Buprenorphine administration caused excitatory phenomena (restlessness and head shaking). Heart rate, cardiac index, and arterial blood pressure were significantly increased after buprenorphine administration until the end of the observational period (120 minutes). Minimal changes were found in arterial blood gas tensions. Abdominal auscultation scores decreased significantly from baseline for 4 hours after buprenorphine administration. CONCLUSIONS AND CLINICAL RELEVANCE: Buprenorphine induced excitement and hemodynamic stimulation with minimal changes in arterial blood gas tensions. These effects may impact the clinical use of buprenorphine in horses. Further studies are indicated to investigate the effects of buprenorphine on gastrointestinal motility and fecal output.     

Cardiovascular effects of xylazine and detomidine in horses

The cardiovascular effects of xylazine and detomidine in horses were studied. Six horses were given each of the following 5 treatments, at 1-week intervals: xylazine, 1.1 mg/kg, IV; xylazine, 2.2 mg/kg, IM; detomidine, 0.01 mg/kg, IV; detomidine, 0.02 mg/kg, IV; and detomidine, 0.04 mg/kg, IM. All treatments resulted in significantly decreased heart rate, increased incidence of atrioventricular block, and decreased cardiac output and cardiac index; cardiac output and cardiac index were lowest following IV administration of 0.02 mg of detomidine/kg. Mean arterial pressure was significantly reduced for various periods with all treatments; however, IV administration of 0.02 mg of detomidine/kg caused hypertension initially. Systemic vascular resistance was increased by all treatments. Indices of ventricular contractility and relaxation, +dP/dt and -dP/dt, were significantly depressed by all treatments. Significant changes were not detected in stroke volume or ejection fraction. The PCV was significantly reduced by all treatments. Respiratory rate was significantly decreased with all treatments, but arterial carbon dioxide tension did not change. Arterial oxygen tension was significantly decreased briefly with the 3 IV treatments only.     

Bioavailability of detomidine administered sublingually to horses as an oromucosal gel

Kaukinen, H., Aspegrén, J., Hyyppä, S., Tamm, L., Salonen, J. S. Bioavailability of detomidine administered sublingually to horses as an oromucosal gel. J. vet. Pharmacol. Therap. 34 , 76–81. The objective of the study was to determine the absorption, bioavailability and sedative effect of detomidine administered to horses as an oromucosal gel compared to intravenous and intramuscular administration of detomidine injectable solution. The study was open and randomized, with three sequences crossover design. Nine healthy horses were given 40 μg/kg detomidine intravenously, intramuscularly or administered under the tongue with a 7‐day wash‐out period between treatments. Blood samples were collected before and after drug administration for the measurement of detomidine concentrations in serum. The effects of the route of administration on heart rate and rhythm were evaluated and the depth of sedation assessed. Mean (±SD) bioavailability of detomidine was 22% (±5.3%) after sublingual administration and 38.2% (±7.9%) after intramuscular administration. The sedative effects correlated with detomidine concentrations regardless of the route of administration. We conclude that less detomidine is absorbed when given sublingually than when given intramuscularly, because part of it does not reach the circulation. Sublingual administration of detomidine oromucosal gel at 40 μg/kg produces safe sedation in horses. Slow absorption leads to fewer and less pronounced adverse effects than the more rapid absorption after intramuscular injection.     

The effect of the sedative and analgesic detomidine for laryngoscopy of adult horses and foals]

Detomidine was used in this field trial effectively as a sedative and analgesic for laryngoscopic examinations in a total of 193 foals and 806 mature horses (Hanoverians). Detomidine was given either i.v. in foals 3 to 11 months old (20 micrograms/kg) and in mature horses (15 micrograms/kg), or i.m. in foals below 6 months of age (35 micrograms/kg). After i.v. administration, laryngoscopy was tolerated in more than 90% of all animals without additional use of a twitch, while in foals treated i.m. more than 70% required a twitch in order to enable this procedure. The effectiveness of detomidine was influenced by dose, route of administration, the time interval between treatment and examination and the degree of excitement before treatment, but not by sex. Profound bradycardia was evident in all treated animals, but arrhythmias were seen only in animals older than 4 months and were more pronounced in horses with a lower resting heart rate. These cardiovascular responses never endangered any of the treated animals. A transient dyspnea was seen in 13 foals (6.7%) and 10 horses (1.2%). Other side effects were rare. The foaling rate of 297 mares treated at any time during the first 8 months of pregnancy was 66.7%. A comparison with 5499 untreated, contemporary controls revealed a foaling rate of 61.0%. Hence treatments had no adverse effects on pregnancies.     

Pharmacokinetics of detomidine administered to horses at rest and after maximal exercise

Reason for performing study: Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. Objectives: To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. Methods: Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, horses were treated with detomidine. Each horse was treated with the same dose of detomidine on a second occasion a minimum of 14 days later while standing in a stocks. Samples of heparinised blood were obtained at various time points on both occasions. Plasma detomidine concentrations were determined by liquid chromatographymass spectrometry. The plasma concentration vs. time data were analysed by nonlinear regression analysis. Results: Median back‐extrapolated time zero plasma concentration was significantly lower and median plasma half‐life and median mean residence time were significantly longer when detomidine was administered after exercise compared to administration at rest. Median volume of distribution was significantly higher after exercise but median plasma clearance was not different between the 2 administrations. Conclusions and potential relevance: Detomidine i.v. is more widely distributed when administered to horses immediately after exercise compared to administration at rest resulting in lower peak plasma concentrations and a slower rate of elimination. The dose requirement to produce an equivalent effect may be higher in horses after exercise than in resting horses and less frequent subsequent doses may be required to produce a sustained effect.     

Cardiovascular effects of medetomidine, detomidine and xylazine in horses

The cardiovascular effects of medetomidine, detomidine, and xylazine in horses were studied. Fifteen horses, whose right carotid arteries had previously been surgically raised to a subcutaneous position during general anesthesia were used. Five horses each were given the following 8 treatments: an intravenous injection of 4 doses of medetomidine (3, 5, 7.5, and 10 microg/kg), 3 doses of detomidine (10, 20, and 40 microg/kg), and one dose of xylazine (1 mg/kg). Heart rate decreased, but not statistically significant. Atrio-ventricular block was observed following all treatments and prolonged with detomidine. Cardiac index (CI) and stroke volume (SV) were decreased with all treatments. The CI decreased to about 50% of baseline values for 5 min after 7.5 and 10 microg/kg medetomidine and 1 mg/kg xylazine, for 20 min after 20 microg/kg detomidine, and for 50 min after 40 microg/kg detomidine. All treatments produced an initial hypertension within 2 min of drug administration followed by a significant decrease in arterial blood pressure (ABP) in horses administered 3 to 7.5 microg/kg medetomidine and 1 mg/kg xylazine. Hypertension was significantly prolonged in 20 and 40 microg/kg detomidine. The hypotensive phase was not observed in 10 microg/kg medetomidine or detomidine. The changes in ABP were associated with an increase in peripheral vascular resistance. Respiratory rate was decreased for 40 to 120 min in 5, 7.5, and 10 microg/kg medetomidine and detomidine. The partial pressure of arterial oxygen decreased significantly in 10 microg/kg medetomidine and detomidine, while the partial pressure of arterial carbon dioxide did not change significantly. Medetomidine induced dose-dependent cardiovascular depression similar to detomidine. The cardiovascular effects of medetomidine and xylazine were not as prolonged as that of detomidine. KEY WORDS: cardiovascular effect, detomidine, equine, medetomidine, xylazine.     

Antagonism of detomidine sedation with atipamezole in horses

The reversal of detomidine-induced sedation with iv atipamezole was studied in 6 horses. All horses were injected iv with 10 μg and 20 μg/kg bwt detomidine and 15 min later this was followed by 6-, 8- and 10-fold doses of iv atipamezole. Atipamezole caused a quick arousal in all horses with minor side effects. Bradycardia, rhythm disturbances and head ptosis caused by detomidine were not abolished completely at the end of the 15 min observation period, even with the highest atipamezole doses. All horses remained slightly sedated but without ataxia. There were no significant differences in head height, heart rate and sedation score between the different doses of atipamezole for either dose of detomidine. According to the degree of sedation, doses of 100 μg to 160 μg/kg bwt atipamezole are adequate to antagonise detomidine-induced sedation in the horse.     

The sedative and analgesic effects of detomidine-butorphanol and detomidine alone in donkeys

Butorphanol and detomidine constitute an effective combination for sedation and analgesia in horses. This trial was undertaken to assess the effectiveness of this combination in donkeys. The detomidine and butorphanol were given intravenously one after the other. A dose of 10 microg/kg of detomidine and 25 microg/kg of butorphanol was used. Sedation is easily extended by additional doses of butorphanol. The average dose of detomidine was 11.24 microg/kg and that of butorphanol was 28.0 microg/kg. Four donkeys in the detomidine group required additional sedation and analgesia. Detomidine alone did not totally eliminate coronary band pain. Heart rates dropped significantly in the first minute after the injection of the combination. One donkey developed an atrioventricular block, while another developed a sino-atrial block. Four donkeys developed a Cheyne-Stokes respiratory pattern. The combination of detomidine and butorphanol is an effective combination for sedation and analgesia of donkeys for standing procedures.     

The influence of atipamezole on the cardiovascular effects of detomidine in horses

The reversal of the cardiovascular effects of the α₂-adrenoceptor agonist detomidine by the α₂-antagonist atipamezole was studied. Nine horses were given detomidine 20 μg/kg iv. On a separate occasion they were given atipamezole 100 μg/kg iv 15 mins after the detomidine injection. Blood gas tensions were measured and clinical signs of sedation were also observed. Bradycardia and the frequency of heart blocks induced by detomidine were reduced after atipamezole and blood pressure decreased. These reversal effects of atipamezole were of short duration (a few minutes) at the dose level tested. Two of the nine horses exhibited premature depolarisations after administration of detomidine, but not after atipamezole injection. PaO₂ decreased and PaCO₂ increased slightly after detomidine injection, but the arterial pH was within reference values or slightly elevated. Administration of atipamezole did not alter these values. Base excess rose after detomidine, and it decreased more quickly towards the baseline level, when the horses were given detomidine alone. No clinical adverse effects were seen from the administration of atipamezole. Atipamezole may be beneficial, if detomidine-induced bradycardia needs to be reversed in horses.     

Cardiovascular effects of insufflation of the abdomen with carbon dioxide in standing horses sedated with detomidine

OBJECTIVE: To determine the cardiovascular effects of 60 minutes of abdominal insufflation with CO2 to an intra-abdominal pressure of 15 mm Hg in standing horses receiving a constant rate infusion of detomidine. ANIMALS: 5 horses. PROCEDURE: Horses were randomly allocated into treatment or control groups. A washout period of a minimum of 7 days separated the 2 experimental periods of the crossover study. Catheters were placed into the right atrium, pulmonary artery, jugular vein, and right transverse facial artery after lidocaine infiltration. All horses were sedated with detomidine (8.54 microg/kg/h, i.v.). Horses in the treatment group received abdominal insufflation with CO2 via a laparoscopic cannula to a final and constant intra-abdominal pressure of 15 mm Hg for 60 minutes. Systemic arterial pressure, right atrial pressure, heart rate, cardiac output, core body temperature, and the pH and gas tensions of arterial and mixed venous blood were obtained. Cardiac index and systemic vascular resistance were calculated. Data were collected in 3 stages: preinsufflation (-10 and -5 minutes), insufflation (0, 15, 30, 45, and 60 minutes), and postinsufflation (70 and 80 minutes). The quality of sedation and level of analgesia were determined. RESULTS: The PaO2 of horses in the treatment group was significantly higher after 60 minutes of pneumoperitoneum than in the control group. Core body temperature decreased significantly from baseline in both groups. CONCLUSIONS AND CLINICAL RELEVANCE: A 60-minute period of abdominal insufflation to an intra-abdominal pressure of 15 mm Hg did not induce significant cardiovascular abnormalities in healthy horses.     

Clinical effects of detomidine with or without atropine used for arthrocentesis in horses

The effectiveness of detomidine with or without atropine sulfate premedication in producing sedation and analgesia for arthrocentesis was studied in 12 horses. The effects were evaluated by monitoring heart and respiratory rates, borborygmi, distance from the lower lip to the floor, systolic blood pressure, and response to needle insertion. Either atropine or saline (as a placebo) was administered immediately prior to detomidine. All drugs were administered intravenously. Measurements were taken prior to drug injection and at 1, 5, 10, 15, 20, 25, 30, 40, 50, 60, 120, 180 and 240 minutes postinjection. Detomidine with atropine resulted in significantly higher heart rates than detomidine without atropine for the three hours of observation. Borborygmi were significantly decreased for four hours following detomidine with atropine and for three hours following detomidine without atropine, when compared to preinjection levels. Systolic blood pressure was significantly increased for 15 minutes following detomidine and atropine compared to the preinjection level. The head was markedly lowered for 60 minutes with either treatment. Atropine prevented the bradyarrhythmia and bradycardia induced by detomidine, but it induced a tachycardia. A satisfactory response for needle insertion and adequate synovial fluid aspiration was achieved in 95% of the trials with detomidine, with or without atropine sulfate premedication. The results suggest that, although atropine prevents bradyarrhythmia and bradycardia following detomidine, administering detomidine without atropine is satisfactory for arthrocentesis in untrained horses.     

Cardiorespiratory and metabolic effects of xylazine, detomidine, and a combination of xylazine and acepromazine administered after exercise in horses

OBJECTIVE: To determine sedative, cardiorespiratory and metabolic effects of xylazine hydrochloride, detomidine hydrochloride, and a combination of xylazine and acepromazine administered i.v. at twice the standard doses in Thoroughbred horses recuperating from a brief period of maximal exercise. ANIMALS: 6 adult Thoroughbreds. PROCEDURE: Horses were preconditioned by exercising them on a treadmill to establish a uniform level of fitness. Each horse ran 4 simulated races, with a minimum of 14 days between races. Simulated races were run at a treadmill speed that caused horses to exercise at 120% of their maximal oxygen consumption. Horses ran until they were fatigued or for a maximum of 2 minutes. One minute after the end of exercise, horses were treated i.v. with xylazine (2.2 mg/kg of body weight), detomidine (0.04 mg/kg), a combination of xylazine (2.2 mg/kg) and acepromazine (0.04 mg/kg), or saline (0.9% NaCl) solution. Treatments were randomized so that each horse received each treatment once, in random order. Cardiopulmonary indices were measured, and samples of arterial and venous blood were collected immediately before and at specific times for 90 minutes after the end of each race. RESULTS: All sedatives produced effective sedation. The cardiopulmonary depression that was induced was qualitatively similar to that induced by administration of these sedatives to resting horses and was not severe. Sedative administration after exercise prolonged the exercise-induced increase in body temperature. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of xylazine, detomidine, or a combination of xylazine-acepromazine at twice the standard doses produced safe and effective sedation in horses that had just undergone a brief, intense bout of exercise.