Clinical evaluation of established optimal immobilizing doses of medetomidine-ketamine in captive reindeer (Rangifer tarandus tarandus).

OBJECTIVE: To evaluate clinical effects and repeatability of clinical effects for an optimal immobilizing dose of a combination of medetomidine hydrochloride (MED) and ketamine hydrochloride (KET) in reindeer (Rangifer tarandus tarandus). ANIMALS: 12 healthy 6- to 8-month old reindeer. PROCEDURE: Each reindeer was immobilized once with an initial dose (combination of 0.06 mg of MED/kg of body weight and 0.3 mg KET/kg) and twice with an optimal dose of MED-KET. Reversal was achieved with 5 mg of atipamezole/mg of MED injected 45 minutes after MED-KET administration. Observational variables were recorded. Oxygen saturation of arterial hemoglobin measured by pulse oximetry (Spo2), respiratory rate (RR), heart rate (HR), and rectal temperature (RT) were recorded 10, 25, and 40 minutes after immobilization. RESULTS: Mean time to first sign of sedation and time until a recumbent animal lifted its head were significantly reduced for reindeer given the optimal dose, compared with the initial dose. Mean Spo2 remained > 90% during initial immobilization; this value was significantly lower for the optimal dose, but increased during immobilization from 85 to 89%. At all doses, RR increased significantly throughout the recorded period; however, RT and HR were constant. Except for time until reindeer stood, all time variables, Spo2, RR, RT, and HR were repeatable. CONCLUSION AND CLINICAL RELEVANCE: mmobilization of captive reindeer achieved by use of the optimal dose established here is clinically acceptable, although Spo2 should be carefully monitored. Administration of the optimal dose produced the same clinical effect during repeated immobilization of the same reindeer.

Determination of optimal immobilizing doses of a medetomidine hydrochloride and ketamine hydrochloride combination in captive reindeer.

OBJECTIVE: To establish optimal immobilizing doses of medetomidine hydrochloride (MED) with ketamine hydrochloride (KET) for hand- and dart-administered injections in captive reindeer. ANIMALS: 12 healthy 6- to 9-month-old reindeer (Rangifer tarandus tarandus). Procedure An optimal dose was defined as a dose resulting in an induction time of 150 to 210 seconds, measured from the time of IM injection until recumbency. Initially, each stalled reindeer was immobilized by hand-administered injection. If the induction time was > 210 seconds, the dose was doubled for the next immobilization procedure. If it was < 150 seconds, the dose was halved for the next immobilization procedure. This iteration procedure was continued for each reindeer until an optimal dose was found. Later the reindeer was placed in a paddock and darted with its optimal dose as determined by hand-administered injection. Adjusting to a linear relationship between dose and induction time, optimal darting doses for each reindeer were predicted and later verified. RESULTS: The established mean optimal hand- and dart-administered doses were 0.10 mg of MED/kg of body mass with 0.50 mg of KET/kg, and 0.15 mg of MED/kg with 0.75 mg of KET/kg, producing mean induction times of 171 seconds and 215 seconds, respectively. The mean induction time after darting was 5 seconds greater than the upper limit of the predefined time interval. CONCLUSIONS AND CLINICAL RELEVANCE: The higher dose requirement of MED-KET administration outdoors, compared with indoors, was explained by factors inherent in the darting technique and the different confinements. The iteration and the prediction methods seem applicable for determination of optimal doses of MED-KET in reindeer. The iteration and the prediction procedures may be used to reduce the number of experimental animals in dose-response studies in other species.

The effects of medetomidine and its reversal with atipamezole on plasma glucose, cortisol and noradrenaline in cattle and sheep.

In the present study, we report the effect of medetomidine followed by atipamezole on plasma glucose, cortisol and noradrenaline in calves, cows and sheep. Eight calves, eight lactating dairy cows and eight adult female sheep were included in a crossover trial. The animals were injected i.v. with medetomidine (40 microg/kg), followed 60 min later by atipamezole i.v. (200 microg/kg) or saline. The wash-out period between experiments was 1 or 2 weeks. In every animal, medetomidine induced a marked hyperglycaemia, which was reversed by atipamezole. Cortisol levels increased significantly in cows and sheep, reaching levels 4-8-fold higher than the baseline levels 25-45 min after injection of medetomidine. Atipamezole did not affect the cortisol levels, except in sheep where an increase was observed. Plasma levels of noradrenaline decreased in cows and sheep after medetomidine injection, reflecting the inhibition of sympathetic activity by the drug. After injection of the antagonist, there was a large increase in noradrenaline levels. In conclusion, a high dose of medetomidine does not seem to reduce the overall endocrine stress response in cattle and sheep, which has previously been reported in other species.

Experimental Narthecium ossifragum nephrotoxicity in cervids from Norway.

One moose (Alces alces), two red deer (Cervus elaphus), two reindeer (Rangifer tarandus) and two fallow deer (Dama dama) were dosed intraruminally with an aqueous extract made from 30 g of bog asphodel (Narthecium ossifragum) (wet weight) per kg live weight. The moose and one of the two reindeer were mildly depressed and had reduced appetite 3 to 7 days and 1 to 4 days after dosing, respectively. The serum creatinine and urea concentrations increased markedly in the moose and red deer, and moderately in the reindeer. No increase in serum creatinine and urea was observed in the fallow deer. Histopathological examination of the kidneys of the animals, killed 8 to 10 days after dosing, revealed tubular epithelial cell degeneration, necrosis, and regeneration in the moose, red deer and reindeer. The renal lesions were severe in the moose, moderate in the red deer and mild in the reindeer. No histopathological lesions were seen in the kidneys of the fallow deer.

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.

Pharmacokinetics of medetomidine and atipamezole in dairy calves: an agonist-antagonist interaction.

Medetomidine and atipamezole are licensed for use in dogs and cats in several countries and are highly selective and specific alpha2-adrenoceptor agents. The pharmacokinetics of the agonist medetomidine and the antagonist atipamezole were studied in a cross-over trial in eight dairy calves. The animals were injected intravenously (i.v.) with medetomidine (40 microg/kg i.v.), followed by atipamezole (200 microg/kg i.v.) or saline after 60 min. The wash-out period between experiments was 1 week. Drug concentrations in plasma were determined using HPLC. Atipamezole significantly (P < 0.05) increased the AUMC and MRT of medetomidine due to an increase in the medetomidine concentration when atipamezole was injected i.v. The mean increment in medetomidine concentration was 6.4 ng/mL, increased levels having a mean duration of 39.4 min. Other pharmacokinetic parameters of medetomidine were not significantly altered by atipamezole. Sedative effects of the agonist, and the effectiveness of the antagonist were recorded. All the animals relapsed into sedation on average 80 min after reversal with atipamezole. It is likely that the increase in medetomidine concentration after the injection of atipamezole i.v. results from displacement of medetomidine from alpha2-adrenoceptors in highly perfused tissues.