A pharmacokinetic study including some relevant clinical effect of medetomidine and atipamezole in lactating dairy cows

Medetomidine is the most potent and selective alpha2-agonist used in veterinary medicine and its effects can be antagonized by the alpha2-antagonist atipamezole. The pharmacokinetics of medetomidine and atipamezole were studied in a cross-over trial in eight lactating dairy cows. The animals were injected intravenously (i.v.) with medetomidine (40 microg/kg) followed by atipamezole i.v. (200 microg/kg) or saline i.v. after 60 min. Drug concentrations in plasma were measured by HPLC. After the injection of atipamezole, the concentration of medetomidine in plasma increased slightly, the mean increment being 2.7 ng/mL and the mean duration 12.1 min. However, atipamezole did not alter the pharmacokinetics of medetomidine. It is likely that the increase in medetomidine concentration is caused by displacement of medetomidine by atipamezole in highly perfused tissues. The volume of distribution at steady state (Vss) for medetomidine followed by saline and medetomidine followed by atipamezole was 1.21 and 1.32 L/kg, respectively, whereas the total clearance (Cl) values were 24.2 and 25.8 mL/min x kg. Vss and Cl values for atipamezole were 1.77 mL/kg and 48.1 mL/min x kg, respectively. Clinically, medetomidine significantly reduced heart rate and increased rectal temperature for 45 min. Atipamezole reversed the sedative effects of medetomidine. However, all the animals, except one, relapsed into sedation at an average of 80 min after injection of the antagonist.     

Sedative and cardiopulmonary effects of medetomidine hydrochloride and xylazine hydrochloride and their reversal with atipamezole hydrochloride in calves

OBJECTIVE: To assess the sedative and cardiopulmonary effects of medetomidine and xylazine and their reversal with atipamezole in calves. ANIMALS: 25 calves. PROCEDURES: A 2-phase (7-day interval) study was performed. Sedative characteristics (phase I) and cardiopulmonary effects (phase II) of medetomidine hydrochloride and xylazine hydrochloride administration followed by atipamezole hydrochloride administration were evaluated. In both phases, calves were randomly allocated to receive 1 of 4 treatments IV: medetomidine (0.03 mg/kg) followed by atipamezole (0.1 mg/kg; n = 6), xylazine (0.3 mg/kg) followed by atipamezole (0.04 mg/kg; 7), medetomidine (0.03 mg/kg) followed by saline (0.9% NaCl; 6) solution (10 mL), and xylazine (0.3 mg/kg) followed by saline solution (10 mL; 6). Atipamezole or saline solution was administered 20 minutes after the first injection. Cardiopulmonary variables were recorded at intervals for 35 minutes after medetomidine or xylazine administration. RESULTS: At the doses evaluated, xylazine and medetomidine induced a similar degree of sedation in calves; however, the duration of medetomidine-associated sedation was longer. Compared with pretreatment values, heart rate, cardiac index, and PaO(2) decreased, whereas central venous pressure, PaCO(2), and pulmonary artery pressures increased with medetomidine or xylazine. Systemic arterial blood pressures and vascular resistance increased with medetomidine and decreased with xylazine. Atipamezole reversed the sedative and most of the cardiopulmonary effects of both drugs. CONCLUSIONS AND CLINICAL RELEVANCE: At these doses, xylazine and medetomidine induced similar degrees of sedation and cardiopulmonary depression in calves, although medetomidine administration resulted in increases in systemic arterial blood pressures. Atipamezole effectively reversed medetomidine- and xylazine-associated sedative and cardiopulmonary effects in calves.     

Reversal of medetomidine-induced sedation in reindeer (Rangifer tarandus tarandus) with atipamezole increases the medetomidine concentration in plasma

The pharmacokinetics of two potent α₂-adrenoceptor agents that can be used for immobilization (medetomidine) and reversal (atipamezole) of the sedation in mammals, were studied in three reindeer ( Rangifer tarandus tarandus) in winter and again in summer. Medetomidine (60 μg/kg) was injected intravenously (i.v.), followed by atipamezole (300 μg/kg) intravenously 60 min later. Drug concentrations in plasma were measured by HPLC. The administration of atipamezole resulted in an immediate 2.5–3.5 fold increase in the medetomidine concentration in plasma. Clearance for medetomidine (median 19.3 mL/min·kg) was lower than clearance for atipamezole (median 31.0 mL/min·kg). The median elimination half-lives of medetomidine and atipamezole in plasma were 76.1 and 59.9 min, respectively. The animals became resedated 0.5–1 h after the reversal with atipamezole. Resedation may be explained by the longer elimination half-life of medetomidine compared to atipamezole.     

Adrenocorticotropic hormone and cortisol in calves after corticotropin-releasing hormone.

The aim for this study was to analyze responsiveness of the hypothalamo-pituitary-adrenocortical axis to exogenous bovine corticotropin-releasing hormone (bCRH) in calves. Two dose-response studies were carried out, using either bCRH alone (dose rates of 0, .01, .03, and .1 microg bCRH/kg live weight) or in combination with arginine-vasopressin (bCRH:AVP, 0:0, .1:.05, .5:.25, and 1:.5 microg kg live weight). The bCRH was administered i.v. to calves (n = 5 to 7 per dose) housed individually or in groups. Serial blood samples were obtained from before to 300 min after injection and analyzed for plasma ACTH and cortisol concentrations. The lowest bCRH dose that produced a response in all calves was .1 microg/kg. In the experiment using bCRH with AVP, increasing the bCRH dose from .1 to 1 microg/kg resulted in an increase in peak ACTH concentration (321 vs. 2,003 pg/mL) but did not significantly affect the peak cortisol concentration (37 vs. 40 ng/mL). The time to reach the peak cortisol concentration increased with the dose of bCRH with AVP (from 38 to 111 min). The ACTH and cortisol concentrations determined at any time between 20 and 90 min after bCRH injection were correlated to the integrated responses calculated as areas under the ACTH and the cortisol curves (r between .61 and .99, P<.05). In comparison with results from studies in humans, pigs, and sheep, our data showed that the pituitary of calves seems less sensitive to CRH than that of other mammals, despite a greater capacity to produce ACTH. Moreover, the calf's adrenals seem to have a lower capacity to produce cortisol than adrenals of other mammals. As in other species, it seems that AVP enhances the release of ACTH and cortisol. For CRH challenge to be used in calves, we suggest injecting at least .1 microg of bCRH/kg live weight either with or without AVP and taking several blood samples before injection and between 20 and 90 min after injection.     

Effect of medetomidine and its antagonism with atipamezole on stress-related hormones, metabolites, physiologic responses, sedation, and mechanical threshold in goats

OBJECTIVE: To evaluate the effects of medetomidine and its antagonism with atipamezole in goats. STUDY DESIGN: Prospective randomized crossover study with 1 week between treatments. ANIMALS: Six healthy 3-year-old neutered goats (three male and three female) weighing 39.1-90.9 kg (60.0 +/- 18 kg, mean +/- SD). METHODS: Goats were given medetomidine (20 microg kg(-1), IV) followed, 25 minutes later, by either atipamezole (100 microg kg(-1), IV) or saline. Heart and respiratory rate, rectal temperature, indirect blood pressure, and mechanical threshold were measured, and sedation and posture were scored and blood samples obtained to measure epinephrine, norepinephrine, free fatty acids, glucose, and cortisol concentrations at baseline (immediately before medetomidine), 5 and 25 minutes after medetomidine administration, and at 5, 30, 60, and 120 minutes after the administration of antagonist or saline. Parametric and nonparametric tests were used to evaluate data; p < 0.05 was considered significant. RESULTS: Medetomidine decreased body temperature, heart rate, and respiratory rate and increased mean arterial blood pressure, cortisol, and glucose. Recumbency occurred 89 +/- 50 seconds after medetomidine administration. All goats were standing 86 +/- 24 seconds after atipamezole administration whereas all goats administered saline were sedate and recumbent at 2 hours. Tolerance to compression of the withers and metacarpus increased with medetomidine. From 5 to 120 minutes after saline or atipamezole administration, there were differences in body temperature, glucose, and cortisol but none in heart rate or blood pressure. Three of the six goats receiving saline developed bloat; five of six urinated. After atipamezole, four of six goats developed piloerection and all goats were agitated and vocalized. CONCLUSION: At the doses used, atipamezole antagonized the effects of medetomidine on recumbency, sedation, mechanical threshold, and the increase in glucose. Atipamezole increased the rate of return of cortisol toward baseline, and prevented further decline in rectal body temperature. CLINICAL RELEVANCE: Atipamezole may be used to antagonize some, but not all effects of medetomidine.     

Influence of yohimbine and atipamezole on haemodynamics and ECG after lumbosacral subarachnoid administration of medetomidine in goats

Effects of intravenous yohimbine and atipamezole on haemodynamics and electrocardiogram (ECG) were studied after lumbosacral subarachnoid administration of medetomidine in eight goats. All goats received lumbosacral subarachnoid medetomidine at a dosage of 0.01 mg/kg followed by yohimbine (0.25 mg/kg) or atipamezole (0.005 mg/kg) intravenously 45 min after administration of medetomidine, in a randomized crossover design, in right lateral recumbency keeping a gap of 1 week between each trial. Heart rate, respiratory rate, rectal temperature, mean arterial pressure (MAP), mean central venous pressure (MCVP) and ECG were determined. Goats were observed for sedation and urination. All goats showed sedation and depression after medetomidine administration became alert within 2-5 min after reversal. Bradycardia and bradypnoea were the consistent findings after medetomidine injection. Tachycardia and tachypnoea were recorded within 2-5 min after reversal in both groups. A decrease in MAP and an increase in MCVP were seen after medetomidine administration in both groups. Effects of yohimbine and atipamezole on the reversal of MAP and MCVP were more or less the same and statistically non-significant (P > 0.05) in all animals. The ECG changes were non-significant (P > 0.05) in both groups. It is concluded that in the given dose rates both yohimbine (0.25 mg/kg) and atipamezole (0.005 mg/kg) produced equal reversal of the sedation, CNS depression, cardiopulmonary and ECG changes induced by subarachnoid administration of medetomidine in goats indicating that most of the actions of medetomidine were mediated via activation of alpha2-adrenergic receptors.     

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.     

Anaesthesia of roan antelope (Hippotragus equinus) with a combination of A3080, medetomidine and ketamine

A dose range was determined for anaesthesia of 20 recently boma-captured roan antelope (Hippotragus equinus) with the synthetic opiate A3080 combined with medetomidine and ketamine. A dose of 10-30 micro/kg A3080 (x = 20+/-8 microg/kg) combined with 5-21 microg/kg medetomidine (x = 13+/-7 microg/kg) plus 0.29-1.11 mg/kg ketamine (x = 0.71+/-0.24 mg/kg) was found to be safe and effective for the field conditions in this study. The anaesthesia produced by this drug combination was predictable and characterised by a short induction time, good muscle relaxation, and acceptable physiological parameters for anaesthesia periods ranging from 49-103 min (x = 64+/-19 min). The wide range (3-4-fold) of doses with acceptable results is also an indication that this drug combination has a wide margin of safety in roan antelope, making it desirable for field use. When 2 dose levels (2-3-fold dif ference) were retrospectively evaluated, no statistical difference was found in induction times, and no observable clinical differences in the anaesthetic episodes were seen. Based on this study, the recommended dose range in roan antelope for this combination is 10-13 microg/kg A3080, 5-6 microg/kg medetomidine and 0.3-0.6 mg/kg ketamine. The anaesthesia produced by this combination was rapidly and completely reversed by i.m. or i.v. injections of naltrexone at 30 times the A3080 dose (x = 0.60+/-0.25 mg/kg) and atipamezole at 3 times the medetomidine dose (x = 38+/-20 microg/kg). No residual effects from ketamine were noted following reversal of A3080 and medetomidine. No mortality was associated with this protocol.     

Cardiopulmonary assessment of medetomidine, ketamine, and butorphanol anesthesia in captive Thomson's gazelles (Gazella thomsoni).

This investigation evaluated the cardiopulmonary effects of medetomidine, ketamine, and butorphanol anesthesia in captive juvenile Thomson's gazelles (Gazella thomsoni). Butorphanol was incorporated to reduce the dose of medetomidine necessary for immobilization and minimize medetomidine-induced adverse cardiovascular side effects. Medetomidine 40.1 +/- 3.6 microg/kg, ketamine 4.9 +/- 0.6 mg/kg, and butorphanol 0.40 +/- 0.04 mg/kg were administered intramuscularly by hand injection to nine gazelles. Times to initial effect and recumbency were within 8 min postinjection. Cardiopulmonary status was monitored every 5 min by measuring heart rate, respiratory rate, indirect blood pressure, end-tidal CO2, and indirect oxygen-hemoglobin saturation by pulse oximetry. Venous blood gases were collected every 15 min postinjection. Oxygen saturations less than 90% in three gazelles suggested hypoxemia. Subsequent immobilized gazelles were supplemented with intranasal oxygen throughout the anesthetic period. Sustained bradycardia (<60 beats per minute, as compared with anesthetized domestic calves, sheep, and goats) was noted in eight of nine gazelles. Heart and respiratory rates and rectal temperatures decreased slightly, whereas systolic, mean, and diastolic blood pressure values were consistent over the anesthetic period. Mild elevations in end tidal CO2 and PCO2 suggested hypoventilation. Local lidocaine blocks were necessary to perform castrations in all seven of the gazelles undergoing the procedure. Return to sternal recumbency occurred within 7 min and return to standing occurred within 12 min after reversal with atipamezole (0.2 +/- 0.03 mg/kg) and naloxone (0.02 +/- 0.001 mg/kg). Medetomidine, ketamine, and butorphanol can be used to safely anesthetize Thomson's gazelles for routine, noninvasive procedures. More invasive procedures, such as castration, can be readily performed with the additional use of local anesthetics.     

The clinical effectiveness of atipamezole as a medetomidine antagonist in the dog

The efficacy of atipamezole, a recently introduced alpha 2-adrenoceptor antagonist, in reversing medetomidine-induced effects in dogs was investigated in a clinical study. Dogs from eight Finnish small-animal hospitals were sedated with a 40-microgram/kg dose of the alpha 2-agonist medetomidine i.m. In the first part of the study (n = 319), a randomized, double-blind design with respect to the dose of atipamezole (0, 80, 160 and 240 micrograms/kg i.m.) was used. In a separate study (n = 358), which was an open trial, the selected dose of atipamezole was 200 micrograms/kg i.m. Atipamezole at dose rates of 80-240 micrograms/kg rapidly and effectively reversed medetomidine-induced deep sedation-analgesia, recumbency and bradycardia. The median arousal time after atipamezole was 3-5 min, and walking time was 6-10 min compared to greater than 30 min for both effects after placebo. Heart rate also increased in a dose-related manner after atipamezole administration. The investigators' overall evaluation of the ability of atipamezole to reverse the effects of medetomidine was 'good' in 90%, and 'moderate' in 9% of cases. Relapse into sedation was reported in three individual cases. Side-effects were minimal. It is concluded that at doses four- to sixfold the medetomidine dose, atipamezole is a highly effective and safe agent in reversing medetomidine-induced sedation-analgesia, recumbency and bradycardia in dogs in veterinary practice.     

Cardiopulmonary effects of a two hour medetomidine infusion and its antagonism by atipamezole in horses and ponies

The cardiopulmonary effects of an intravenous (iv) medetomidine injection (5 μg/kg) followed 5 min later by its infusion at 3.5 μg/kg/h for 115 rnin were studied in 9 horses and ponies. Five minutes after the end of infusion 60 μg/kg atipamezole were given. Physiological data during infusion were compared with pre-sedation values. Stroke volume was reduced significantly 5 min after initial medetomidine injection. Cardiac index was reduced significantly and systemic vascular resistance increased significantly for the first 20 min, but returned towards pre-sedation values after this time. Arterial blood pressures were reduced significantly from 30 min until the end of the procedure (minimum MAP was 102.4 ± 9.61 mmHg). Mixed venous oxygen tension was reduced significantly during the infusion. Respiratory rate fell and PaCO₂- rose significantly from 40 min onward. Other variables showed no significant changes. The horses recovered rapidly after atipamezole was injected. Arterial blood pressures remained significantly lowered, but other cardiovascular variables returned towards pre-sedation values. It is concluded that the infusion of medetomidine at 3.5 μg/kg/h causes minimum cardiopulmonary depression once the effects of an initial 5 μg/kg injection have waned, and so could prove suitable as part of an anaesthetic technique in equidae.     

Immobilisation of impala (Aepyceros melampus) with a ketamine hydrochloride/medetomidine hydrochloride combination, and reversal with atipamezole hydrochloride

A combination of medetomidine hydrochloride (medetomidine) and ketamine hydrochloride (ketamine) was evaluated in 16 boma-confined and 19 free-ranging impalas (Aepyceros melampus) to develop a non-opiate immobilisation protocol. In free-ranging impala a dose of 220 +/- 34 microg/kg medetomidine and 4.4 +/- 0.7 mg/kg ketamine combined with 7500 IU of hyaluronidase induced recumbency within 4.5 +/- 1.5 min, with good muscle relaxation, a stable heart rate and blood pH. PaCO2 was maintained within acceptable ranges. The animals were hypoxic with reduced oxygen saturation and low PaO2 in the presence of an elevated respiration rate, therefore methods for respiratory support are indicated. The depth of sedation was adequate for minor manipulations but additional anaesthesia is indicated for painful manipulations. Immobilisation was reversed by 467 +/- 108 microg/kg atipamezole hydrochloride (atipamezole) intramuscularly, but re-sedation was observed several hours later, possibly due to a low atipamezole:medetomidine ratio of 2:1. Therefore, this immobilisation and reversal protocol would subject impalas to possible predation or conspecific aggression following reversal if they were released into the wild. If the protocol is used on free-ranging impala, an atipamezole:medetomidine ratio of 5:1 should probably be used to prevent re-sedation.     

Comparison of etorphine-detomidine and medetomidine-ketamine anesthesia in captive addax (Addax nasomaculatus).

Thirty-five anesthetic events involving 15 captive addax (Addax nasonzaculatus) were performed between August 1998 and February 2002 using a combination of etorphine (33.7 +/- 7.9 microg/kg) and detomidine (21.9 +/- 4.6 microg/ kg) or a combination of medetomidine (57.4 +/- 8.6 microg/kg) and ketamine (1.22 +/- 0.3 microg/kg), with or without supplemental injectable or inhalant anesthetic agents. Etorphine-detomidine anesthesia was antagonized with diprenorphine (107.1 +/- 16.4 microg/kg) and atipamezole (100.9 +/- 42.4 microg/kg). Medetomidine-ketamine anesthesia was antagonized with atipamezole (245.3 +/- 63.4 microg/kg). Animals became recumbent within 5 min when the combination of etorphine and detomidine was used and within 11 min when the combination of medetomidine and ketamine was used. Both drug combinations were suitable for use as primary immobilizing agents producing short-duration restraint and analgesia. Bradycardia was noted with both combinations. Further investigation of the cardiopulmonary effects of both combinations is warranted.     

Renal effects of medetomidine in isoflurane-anesthetized dogs with special reference to its diuretic action

Renal effects of the selective alpha(2)-adrenoceptor agonist, medetomidine, were investigated in anesthetized dogs. Animals were administered medetomidine 20 and 40 microg/kg intravenously (IV) and 80 mug/kg intramuscularly (IM) or 1 ml of saline IV. Urine and blood samples were collected before and at 30, 60, 90 and 120 min following medetomidine injection. Mean arterial blood pressure (MABP), renal blood flow (RBF), glomerular filtration rate (GFR), urine volume (U(v)), urine osmolality (U(osm)), free water clearance (C(H2O)), fractional clearance of sodium (F(Na)), plasma osmolality (P(osm)), plasma glucose levels and plasma antidiuretic hormone (ADH) concentrations were measured. The results showed that IV administration of medetomidine initially increased MABP 5-15 min followed by long-lasting decrease. The initial hypertension was not observed after IM administration, which was accompanied by a more profound hypotensive effects. RBF, GFR, U(v), C(H2O) increased after IV injection and decreased after IM. Medetomidine increased FNa and Posm and decreased U(osm). Plasma glucose levels initially increased and subsequently decreased. Plasma ADH concentration was decreased by IV injection but increased by IM administration. Our data imply that: 1) IV administration of medetomidine at dose rates of 20 and 40 microg/kg results in profound diuresis up to 2 hr; 2) Suppression of ADH release from the CNS is one of the mechanisms of medetomidine-induced diuresis although it may not be the principal one.     

An evaluation of the influence of medetomidine hydrochloride and atipamezole hydrochloride on the arrhythmogenic dose of epinephrine in dogs during halothane anesthesia.

Alterations in the arrhythmogenic dose of epinephrine (ADE) were determined following administration of medetomidine hydrochloride (750 micrograms/M2) and a saline placebo, or medetomidine hydrochloride (750 micrograms/M2), followed by specific medetomidine reversal agent, atipamezole hydrochloride (50 micrograms/kg) 20 min later, in halothane-anesthetized dogs (n = 6). ADE determinations were made prior to the administration of either treatment, 20 min and 4 h following medetomidine/saline or medetomidine/atipamezole administration. Epinephrine was infused for 3 min at increasing dose rates (2.5 and 5.0 micrograms/kg/min) until the arrhythmia criterion (4 or more intermittent or continuous premature ventricular contractions) was reached. The interinfusion interval was 20 min. There were no significant differences in the amount of epinephrine required to reach the arrhythmia criterion following the administration of either treatment. In addition, the ADE at each determination was not different between treatment groups. In this study, the administration of medetomidine to halothane-anesthetized dogs did not alter their arrhythmogenic response to infused epinephrine.     

The pharmacodynamics of thiopental, medetomidine, butorphanol and atropine in beagle dogs

This study evaluated the quality of anaesthesia and some of the haemodynamic effects induced by a combination of thiopental, medetomidine, butorphanol and atropine in healthy beagle dogs ( n  = 12). Following premedication with atropine (ATR, 0.022 mg/kg intravenously (i.v.)) and butorphanol (BUT, 0.22 mg/kg i.v.), medetomidine (MED, 22 μg/kg intramuscularly (i.m.)) was administered followed in 5 min by thiopental (THIO, 2.2 mg/kg i.v.). Heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MBP) were monitored continuously with an ECG and direct arterial blood pressure monitor. Atipamezole (ATI, 110 μg/kg i.v.) was administered to half of the dogs ( n  = 6) following surgery to evaluate the speed and quality of arousal from anaesthesia. Anaesthesia was characterized by excellent muscle relaxation, analgesia and absence of purposeful movement in response to surgical castration. Arousal following antagonism of mede­tomidine was significantly faster ( P  < 0.05) than in unantagonized dogs. Recoveries were smooth but recovery times following atipamezole administration were highly variable among dogs (sternal time range 6–38 min, standing time range 9–56 min). Medetomidine caused a significant ( P  < 0.05) increase in SBP, DBP and MBP. Atropine prevented the medetomidine induced bradycardia. In conclusion, this combination provided adequate surgical anaesthesia in healthy beagle dogs. At the dosages used in this study, it seems prudent that this combination should be reserved for dogs free of myocardial disease.     

Cardiopulmonary and anesthetic effects of medetomidine-ketamine-butorphanol and antagonism with atipamezole in servals (Felis serval).

Seven (three male and four female) 4-7-yr old captive servals (Felis serval) weighing 13.7 +/- 2.3 kg were used to evaluate the cardiopulmonary and anesthetic effects of combined intramuscular injections of medetomidine (47.4 +/- 10.3 microg/kg), ketamine (1.0 +/- 0.2 mg/kg), and butorphanol (0.2 +/- 0.03 mg/kg). Inductions were smooth and rapid (11.7 +/- 4.3 min) and resulted in good muscle relaxation. Significant decreases in heart rate (85 +/- 12 beats/min) at 10 min after injection and respiratory rate (27 +/- 10 breaths/min) at 5 min after injection continued throughout the immobilization period. Rectal temperature and arterial blood pressure did not change significantly. The PaO2 decreased significantly, and PaCO2 increased significantly during immobilization but remained within clinically acceptable limits. Hypoxemia (PaO2 < 60 mm Hg) was not noted, and arterial blood oxygen saturation (SaO2) was greater than 90% at all times. Relative arterial oxygen saturation (SpO2) values, indicated by pulse oximetry, were lower than SaO2 values. All animals could be safely handled while sedated. Administration of atipamezole (236.8 +/- 51.2 microg/kg half i.v. and half s.c.), an alpha2 antagonist, resulted in rapid (4.1 +/- 3 min to standing) and smooth recoveries.     

Determination of an optimal dose of medetomidine-ketamine-buprenorphine for anaesthesia in the Cape ground squirrel (Xerus inauris)

The optimal dose of medetomidine-ketamine-buprenorphine was determined in 25 Cape ground squirrels (Xerus inauris) undergoing surgical implantation of a temperature logger into the abdominal cavity. At the end of anaesthesia, the squirrels were given atipamezole intramuscularly to reverse the effects of medetomidine. The mean dose of medetomidine was 67.6 +/- 9.2microg/kg, ketamine 13.6 +/- 1.9 mg/kg and buprenorphine 0.5 +/- 0.06 microg/kg. Induction time was 3.1 +/- 1.4 min. This produced surgical anaesthesia for 21 +/- 4.2 min. Atipamezole 232 +/- 92 microg/kg produced a rapid recovery. Squirrels were sternally recumbent in 3.5 +/- 2.2 min.     

Reversible anaesthesia of free-ranging lions (Panthera leo) in Zimbabwe

The combination of medetomidine-zolazepam-tiletamine with subsequent antagonism by atipamezole was evaluated for reversible anaesthesia of free-ranging lions (Panthera leo). Twenty-one anaesthetic events of 17 free-ranging lions (5 males and 12 females, body weight 105-211 kg) were studied in Zimbabwe. Medetomidine at 0.027-0.055 mg/kg (total dose 4-11 mg) and zolazepam-tiletamine at 0.38-1.32 mg/kg (total dose 50-275 mg) were administered i.m. by dart injection. The doses were gradually decreased to improve recovery. Respiratory and heart rates, rectal temperature and relative haemoglobin oxygen saturation (SpO2) were recorded every 15 min. Arterial blood samples were collected from 5 lions for analysis of blood gases and acid-base status. For anaesthetic reversal, atipamezole was administered i.m. at 2.5 or 5 times the medetomidine dose. Induction was smooth and all lions were anaesthetised with good muscle relaxation within 3.4-9.5 min after darting. The predictable working time was a minimum of 1 h and no additional drug doses were needed. Respiratory and heart rates and SpO2 were stable throughout anaesthesia, whereas rectal temperature changed significantly over time. Atipamezole at 2.5 times the medetomidine dose was sufficient for reversal and recoveries were smooth and calm in all lions independent of the atipamezole dose. First sign of recovery was observed 3-27 min after reversal. The animals were up walking 8-26 min after reversal when zolazepam-tiletamine doses < 1 mg/kg were used. In practice, a total dose of 6 mg medetomidine and 80 mg zolazepam-tiletamine and reversal with 15 mg atipamezole can be used for either sex of an adult or subadult lion. The drugs and doses used in this study provided a reliable, safe and reversible anaesthesia protocol for free-ranging lions.