Antagonism of medetomidine sedation by atipamezole in pigs.

The efficacy of atipamezole as a medetomidine antagonist was evaluated in pigs. The atipamezole doses (intramuscularly) were 80, 160, 320 and 480 micrograms/kg of body weight, which were one, two, four and six times higher than the preceding medetomidine dose (80 micrograms/kg, intramuscularly). Atipamezole effectively reversed medetomidine-induced sedation, and the optimal action was seen at doses of 160 and 320 micrograms/kg. Recovery from sedation was quick and smooth, and adverse effects such as hyperactivity or tachycardia were minimal with either dose.     

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.     

Investigation of romifidine and detomidine for the clinical sedation of horses

The effects of two intravenous doses of romifidine (80 and 120 microg/kg) and one dose of detomidine (20 microg/kg) were compared in a blinded study in 30 horses requiring to be sedated for routine dental treatment. Several physiological parameters were assessed before and for two hours after the administration of the drugs, and the horses' teeth were rasped 30 minutes after they were administered. Romifidine produced a dose-dependent effect on most parameters. Detomidine at 20 microg/kg was similar to romifidine at 120 microg/kg in the magnitude of its sedative effects, but was similar to romifidine at 80 pg/kg in its duration. There were no significant differences between the three treatments in terms of the clinical procedure score.     

Antagonism of detomidine with tolazoline in isoflurane-anaesthetised ponies

The effects of tolazoline (4.0 mg/kg iv) antagonism of detomidine (0.02 mg/kg iv) were evaluated in isoflurane-anaesthetised, ventilated ponies. Each of 6 ponies received both tolazoline and saline treatment during separate anaesthetic episodes only (no surgery was performed). Detomidine administration produced an increase in blood pressure, decrease in heart rate and decrease in P_aO₂ Tolazoline treatment transiently increased heart rate while blood pressure returned to baseline after both treatments. Arterial oxygenation decreased further after tolazoline treatment while oxgenation recovered towards baseline with saline treatment. No other cardiopulmonary effects were detected. Recovery from anaesthesia tended to be more rapid when detomidine was antagonized. The potential benefit of antagonizing detomidine-induced bradycardia with tolazoline, during isoflurane anaesthesia should be weighed against the potential to produce a decrease in arterial oxygenation. The mechanism for this effect is not clear.     

The use of atropine to control heart rate responses during detomidine sedation in horses

Detomidine is a sedative-analgesic which has a pharmacological profile similar to xylazine. There is evidence that the sedative effects are mediated through alpha-2 adrenoceptors.Cardiopulmonary responses were determined using detomidine as the principal agent and as a preanesthetic prior to the induction of general anesthesia. Compatibility with guaifenesin, sodium thia-mylal and halothane were determined.As in the case of xylazine, detomidine produces a slowing of heart rates. This was found to be either sinus bradycardia or heart block. There may be a corresponding increase in systolic blood pressures. The respiratory pattern is altered through the arterial blood gases and pH data supported evidence of adequate ventilation. The heart rate response to detomidine without anticholinergic treatment was transient and related to he duration of drug action.Atropine sulfate, 0.02 mg/kg i.v. was effective in preventing or treating bradycardia or heart block from detomidine. Heart rates also increased during the administration of guaifenesin and sodium thia-mylal when given 50 min poisit-detomidine.     

Behavioural and cardiovascular effects of medetomidine constant rate infusion compared with detomidine for standing sedation in horses

ObjectiveTo compare the efficacy of a medetomidine constant rate infusion (CRI) with a detomidine CRI for standing sedation in horses undergoing high dose rate brachytherapy.Study designRandomized, controlled, crossover, blinded clinical trial.AnimalsA total of 50 horses with owner consent, excluding stallions.MethodsEach horse was sedated with intravenous acepromazine (0.02 mg kg^–1), followed by an α₂-adrenoceptor agonist 30 minutes later and then by butorphanol (0.1 mg kg^–1) 5 minutes later. A CRI of the same α₂-adrenoceptor agonist was started 10 minutes after butorphanol administration and maintained for the treatment duration. Treatments were given 1 week apart. Each horse was sedated with detomidine (bolus dose, 10 μg kg^–1; CRI, 6 μg kg^–1 hour^–1) or medetomidine (bolus dose, 5 μg kg^–1; CRI, 3.5 μg kg^–1 hour^–1). If sedation was inadequate, a quarter of the initial bolus of the α₂-adrenoceptor agonist was administered. Heart rate (HR) was measured via electrocardiography, and sedation and behaviour evaluated using a previously published scale. Between treatments, behaviour scores were compared using a Wilcoxon signed-rank test, frequencies of arrhythmias with chi-square tests, and HR with two-tailed paired t tests. A p value <0.05 indicated statistical significance.ResultsTotal treatment time for medetomidine was longer than that for detomidine (p = 0.04), and ear movements during medetomidine sedation were more numerous than those during detomidine sedation (p = 0.03), suggesting there may be a subtle difference in the depth of sedation. No significant differences in HR were found between treatments (p ≥ 0.09). Several horses had arrhythmias, with no difference in their frequency between the two infusions.Conclusions and clinical relevanceMedetomidine at this dose rate may produce less sedation than detomidine. Further studies are required to evaluate any clinical advantages to either drug, or whether a different CRI may be more appropriate.     

Reversal of medetomidine sedation by atipamezole in dogs

Atipamezole reversed the sedative effect of medetomidine in twelve laboratory beagles. The dogs were sedated with medetomidine doses of 20, 40 and 80 micrograms/kg body wt i.m. Atipamezole was injected (i.m.) 20 min later at dose rates two, four, six and ten times higher (in micrograms/kg) than the preceding medetomidine dose. Placebo treatment was included in the study. The deeply sedated dogs showed signs of arousal in 3-7 min and took their first steps 4-12 min after atipamezole injection. The dose-related reversal effect of atipamezole proved to be optimal with doses which were four, six or ten times higher than the preceding medetomidine dose. Drowsiness was found 0.5-1 h after atipamezole injection in 41% of the cases. No adverse effects nor cases of over-alertness or excitement were found.     

Medetomidine/ketamine sedation in calves and its reversal with atipamezole

Atipamezole was used to reverse the sedation induced in calves by medetomidine/ketamine. Thirteen claves subjected to umbilical surgery received medetomidine 20 μg/kg bodyweight (bwt) and ketamine 0.5 mg/kg bwt intravenously (iv) from a mixture of the drugs in one syringe. Atipamezole was given at doses of 20 to 60 μg/kg iv and intramuscularly (im) to the calves at the end of the operation. Following the administration of medetomidine and ketamine, PaCO₂ increased whereas pH, PaO₂ and heart rate decreased. Reversing the effects of medetomidine with atipamezole did not cause undesirable effects; recovery was rapid and smooth, most of the animals reached a standing position within 1 to 3 mins after the atipamezole injection.     

Effects of atipamezole on xylazine sedation in ponies.

Atipamezole antagonism of xylazine sedation was evaluated in six ponies. Atipamezole (0.15 mg/kg) or saline was injected intravenously 15 minutes after the ponies had been sedated with xylazine (1.0 mg/kg). Arterial blood pressure and gases, pulse and respiratory rates, the electrocardiogram, nose-to-ground distance and a subjective sedation score were recorded. The pretreatment nose-to-ground distance and PaO2 returned to normal sooner after atipamezole than after saline and the ponies' appetite and normal locomotion also recovered sooner. No significant differences were observed between the effects of saline and atipamezole on the other measurements.     

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.     

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.     

The analgesic effects of intrathecal xylazine and detomidine in sheep and their antagonism with systemic atipamezole

OBJECTIVE: To evaluate the analgesic and adverse side effects of intrathecal (IT) xylazine (XYL) and detomidine (DET) and the subsequent effects of two doses of intravenous (IV) atipamezole (ATI). STUDY DESIGN: Prospective, randomized, cross-over. ANIMALS: Five adult healthy female sheep with mean body mass of 55 +/- 2.3 kg. Material and methods Each sheep underwent four treatments: 1) 50 microg kg(-1) XYL IT and 5 microg kg(-1) ATI IV, 2) 50 microg kg(-1) XYL IT and 2.5 microg kg(-1) ATI IV, 3) 10 microg kg(-1) DET IT and 5 microg kg(-1) ATI IV, 4) 10 microg kg(-1) DET IT and 2.5 microg kg(-1) ATI IV. Pain threshold (TH) was tested by applying pulsed and stepwise incremental direct current to the skin overlying the pastern. The current at the point of foot lift was recorded as the TH. Heart rate (HR), mean arterial pressure, arterial oxygen (PO(2)) and carbon dioxide (PCO(2)) tensions were monitored. Outcomes were derived as differences between baseline assessment and measurements after treatment. Two-way anova was used to analyse drug effects, treatment differences between groups were examined with an F-test or Wilcoxon's rank sum test in case of non-parametric data distribution. p was set at 0.05. RESULTS: Both drugs increased the pain TH, caused small increases in PCO(2), and small decreases in HR, the latter was only significant for XYL recipients. Xylazine produced a significantly higher TH, more rapidly and for longer than DET. Atipamezole only significantly affected PaCO(2) in the XYL group 2. The pain TH was not affected in either group after IV ATI. CONCLUSIONS: At the doses used, IT XYL, and to a lesser extent DET, induced pastern analgesia. Atipamezole 5 microg kg(-1) IV antagonized some side effects without affecting analgesia. CLINICAL RELEVANCE: Intrathecal XYL may be useful as an analgesic in sheep. Its safety is increased because IV ATI antagonizes side effects, but not analgesia.     

Reversal of xylazine-induced sedation in dairy calves with atipamezole: A field trial

Dairy calves immobilized with xylazine (XYL) were given atipamezole-HCl (ATI) at different XYL:ATI dose ratios (w/w) for reversal and the antagonistic effect of xylazine was evaluated. Control animals received saline for comparison. Intramuscular administration of xylazine (0.139–0.357 mg/kg) induced sedation with complete immobilization in all animals (n=195) and there were no spontaneous recoveries before injection of atipamezole or saline. Atipamezole was given 10–81 min and saline 25 min after xylazine administration. Intramuscular administration of atipamezole at XYL:ATI dose ratios of 5:2 (n=11), 10:3 (n=21), 4:1 (n=21) and 5:1 (n=25) effectively antagonized the xylazine-induced immobilization and sedation. The mean times (standard deviation) from injection of atipamezole until the animals were standing for these dose ratio groups were 6.09 (3.12), 5.15 (2.87), 6.35 (2.54) and 7.86 (3.11) min, respectively. The mean time to standing for control animals (n=11) was 94.1 (3.0) min. Intravenous administration of atipamezole at XYL:ATI dose ratios of 10:3 (n=7), 4:1 (n=33), 5:1 (n=16), 8:1 (n=27) and 10:1 (n=9) rapidly reversed the xylazine-induced immobilization and sedation. The mean times (standard deviation) from injection of atipamezole until the animals were standing for these dose ratio groups were 0.98 (0.22), 1.32 (0.48), 1.09 (0.34), 1.39 (0.52) and 1.60 (0.69) min, respectively. The mean time to standing for control animals (n=14) was 88.1 (13.1) min.Animals given high doses of atipamezole (dose ratio groups 5:2 intramuscularly, 10:3 intravenously and 4:1 intravenously) showed signs of excitement while in animals given low doses of atipamezole (dose ratio groups 5:1 intramuscularly and 10:1 intravenously) resedation and relapse into recumbency occurred. Medium doses of atipamezole (dose ratio groups 10:3 intramuscularly, 4:1 intramuscularly, 5:1 intravenously and 8:1 intravenously) did not cause any undesirable side-effects or resedation, and can be recommended for reversal of xylazine-induced sedation in dairy calvesAbbreviations ATI atipamezole-HCl - BW body weight - IM intramuscular - IV intravenous - SD standard deviation - XYL xylazine