Effective immobilizing doses of medetomidine-ketamine in free-ranging, wild Norwegian reindeer (Rangifer tarandus tarandus).

Combinations of medetomidine and ketamine were evaluated in free-ranging, wild Norwegian reindeer (Rangifer tarandus tarandus) as part of a reintroduction program in southwestern Norway in November 1995 and November 1996. The drugs were administered by dart from a helicopter. The mean (SD) effective immobilizing doses for 29 adults (8 males, 21 females) were 0.21 (0.04) mg medetomidine/kg and 1.0 (0.2) mg ketamine/ kg based on estimated body mass. There was no significant difference in mean induction times between males and females. However, animals with optimal hits (shoulder or thigh muscles; n=16) had a significantly shorter (P<0.05) mean induction time than did animals with suboptimal hits (abdomen or flank; n=13), 5.6 (2.2) min and 11.1 (4.7) min, respectively. Inductions were calm, and immobilized animals were maintained in sternal recumbency. Clinical side effects included hypoxemia and hyperthermia in most animals. For reversal, all animals received 5 mg atipamezole per mg medetomidine, half intravenously and half intramuscularly, and the mean (SD) time to standing was 3.7 (3.6) min.

Reversible immobilization of free-ranging Svalbard reindeer (Rangifer tarandus platyrhynchus) with medetomidine-ketamine and atipamezole.

Twenty adult, free-ranging, female Svalbard reindeer (Rangifer tarandus platyrhynchus) were immobilized with medetomidine-ketamine from 30 September through 9 October 1999 at Svalbard, Norway (78 degrees 55'N, 11 degrees 56'E). The animals were approached on foot, and the drugs were administered into the heavy muscles of the shoulder or the thigh by dart syringe injection from 15-25 m. The mean (SD) induction time in 10 animals immobilized with 0.113 (0.009) mg/kg of medetomidine and 2.26 (0.19) mg/kg of ketamine (group 2) was significantly shorter (P < 0.05) than in 10 animals immobilized with 0.215 (0.043) mg/kg of medetomidine and 1.08 (0.21) mg/kg of ketamine (group 1): 6.5 (3.2) versus 14.3 (10.6) min, respectively. Inductions were calm, major clinical side effects were not detected, and there were no significant differences between groups regarding rectal temperature, pulse rate, respiratory rate, or relative arterial oxygen saturation. The 5 mg of atipamezole/1 mg of medetomidine were given half intramuscularly and half subcutaneously for reversal, and the animals were standing within 9.5 (4.5, group 1) and 13.0 (6.4, group 2) min, respectively, after administration of the antagonist.

Antagonistic effects of atipamezole, flumazenil and 4-aminopyridine against anaesthesia with medetomidine, midazolam and ketamine combination in cats.

Antagonistic effects of atipamezole (ATI), flumazenil (FLU) and 4-aminopyridine (4AP) alone and in various combinations after administration of medetomidine-midazolam-ketamine (MED-MID-KET) were evaluated in cats. Animals were anaesthetised with MED (50 microg/kg), MID (0.5 mg/kg) and KET (10 mg/kg) given intramuscularly. Twenty minutes later, physiological saline, ATI (200 microg/kg), FLU (0.1 mg/kg), 4AP (0.5 mg/kg), ATI-FLU, FLU-4AP, ATI-4AP or ATI-FLU-4AP was administered intravenously. FLU, 4AP alone, or FLU-4AP did not effectively antagonise the anaesthesia, hypothermia, bradycardia, and bradypnoea induced by MED-MID-KET. ATI alone was effective. ATI-FLU, ATI-4AP and ATI-FLU-4AP combinations produced an immediate and effective recovery from anaesthesia. The combination of ATI-FLU-4AP was the most effective in antagonising the anaesthetic effects, but was associated with tachycardia, tachypnoea, excitement, and muscle tremors. Combinations with ATI are more effective for antagonising anaesthesia, but ATI-FLU-4AP is not suitable.

Antagonistic effects of yohimbine in pigs anaesthetised with tiletamine/zolazepam and xylazine.

Twelve healthy two-month-old Landrace x Yorkshire pigs of both sexes were randomly assigned to receive either tiletamine and xylazine (zx) or zolazepam and xylazine followed 20 minutes later by yohimbine (zxy). The pigs' scores for immobilisation and analgesia, and their rectal temperature, heart rate, respiration rate, pO(2), pCO(2), alkaline phosphatase, aspartate aminotransferase, glucose and total plasma proteins were determined before and five, 25, 45, 65 and 85 minutes after the administration of the tiletamine/zolazepam and xylazine. The mean total scores for immobilisation and analgesia of the zxy pigs were significantly lower than those of the zx pigs after 85 minutes. The mean rectal temperatures of the zxy pigs were significantly lower than those of zx pigs after 25, 45 and 65 minutes. The mean respiratory rates of the zx pigs were significantly lower than those of zxy pigs after five minutes. The mean pCO(2) of the zxy pigs were significantly lower than those of zx pigs five minutes after the administration of yohimbine. The mean glucose concentration of the zxy pigs were significantly lower than those of zx pigs after 65 and 85 minutes. The mean concentration total protein of the zxy pigs were significantly lower than those of zx pigs throughout the period of anaesthesia. Both groups became laterally recumbent within three minutes. When recovering from anaesthesia, the pigs treated with yohimbine took significantly less time to achieve sternal recumbency (mean [sd] 52.2 [8.9] v 76.2 [20.6] minutes) and less time to be able to stand (mean [sd] 77.0 [9.8] v 98.7 [15.8] minutes), and walk (mean [sd] 81.3 [11.3] v 110.8 [18.6] minutes).

Reversal of medetomidine-ketamine combination anesthesia in rabbits by atipamezole.

This study was performed to determine the optimal reversal dosage of atipamezole on medetomidine-ketamine combination anesthesia. The subject rabbits were divided into five groups (n=5/group), and all were anesthetized with intravenous medetomidine (0.35 mg/kg) and ketamine (5 mg/kg). Atipamezole was administered intravenously 35 min after administration of the medetomidine-ketamine mixture, at doses of a quarter, a half, equal, or two times higher than the preceding medetomidine -ketamine dose according to experimental group. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR) and rectal temperature (RT) were measured every five minutes and the mean arousal time (MAT) was also recorded. This study revealed that the optimal atipamezole dosage to achieve reversal effects is equal to or double the dose of medetomidine. At these dosages, HR and MAP significantly recovered and MAT was significantly shortened with no side effects being observed (p<0.05).

Immobilization of mule deer with thiafentanil (A-3080) or thiafentanil plus xylazine.

We evaluated thiafentanil oxalate (A-3080) for the immobilization of mule deer (Odocoileus hemionus) under laboratory and field conditions. In a crossover experiment comparing recommended (0.1 mg/kg) and 2x recommended thiafentanil doses in captive deer, both produced rapid induction and immobilization. Mean induction was shorter (P = 0.013) for the 2x group (1.9 vs. 3 min); mean reversals for both groups were rapid (recommended = 0.9 min after naltrexone injection; 2x = 1 min) and did not differ (P = 0.29). Six free-ranging mule deer were immobilized with 7 mg thiafentanil and four with 10 mg; mean induction was 2.3 min for both groups (95% confidence interval [CI]: 7 mg, 1.2-3.4; 10 mg, 1.9-2.8), and mean reversal was <1 min for both groups. Of 165 free-ranging deer darted with various combinations of thiafentanil and xylazine, we successfully immobilized 148 (90%). Mean induction ranged from 2.1 to 4.9 min for different drug combinations. Reversals were not compared because naltrexone and yohimbine doses varied, but overall mean reversal was 1.9 min (95% CI, 1.7-2.1 min) after injection of naltrexone and yohimbine intravenously (i.v.); naltrexone:thiafentanil ratios ranging from 10:1 to 43:1 provided mean recoveries ranging from 1.5 to 2.3 min. All 25 deer fitted with radio collars were alive at 30 days postcapture. On the basis of overall reliability and effectiveness, drug volumes, and ease of handling drugged animals, we recommend using a combination of 10-12 mg thiafentanil (0.15-0.2 mg/kg) and 100 mg xylazine to immobilize mule deer; immobilization can be effectively reversed with 100 mg naltrexone or more and 15 mg yohimbine or more i.v. Where feasible, we also recommend the use of transmitter darts when immobilizing mule deer with opioids in order to maximize recovery of darted deer and to ensure that missed darts are found.

Reversible anesthesia of captive California sea lions (Zalophus californianus) with medetomidine, midazolam, butorphanol, and isoflurane.

Two adult California sea lions (Zalophus californianus) were effectively anesthetized 13 times with medetomidine (0.010-0.013 mg/kg), midazolam (0.2-0.26 mg/kg), and butorphanol (0.2-0.4 mg/kg) by i.m. hand or pole syringe injection. For each anesthetic event, atropine (0.02 mg/kg, i.m.) was administered 6-20 min after initial injections, and oxygen administration via face mask or nasal insufflation began at the same time. Light anesthesia was induced in 8-22 min and lasted 13-78 min. During eight of the procedures, isoflurane (0.5-2.0%) was administered via face mask or endotracheal tube for an additional 30-120 min to facilitate longer procedures or surgery. Anesthesia was antagonized with atipamezole (0.05-0.06 mg/kg) and naltrexone (0.1 mg/kg) in seven events, with the addition of flumazenil (0.0002-0.002 mg/kg) in six events. The antagonists were administered by i.m. injection 42-149 min after administration of the induction agents. All sea lions recovered to mild sedation within 4-17 min after administration of the antagonists.

Evaluation of medetomidine-ketamine anesthesia with atipamezole reversal in American alligators (Alligator mississippiensis).

Sixteen captive and wild-caught American alligators (Alligator mississippiensis), seven juveniles (< or = 1 m total length [TL]; 6.75 +/- 1.02 kg), and nine adults (> or = 2 m TL; 36.65 +/- 38.85 kg), were successfully anesthetized multiple times (n = 33) with an intramuscular (i.m.) medetomidine-ketamine (MK) combination administered in either the triceps or masseter muscle. The juvenile animals required significantly larger doses of medetomidine (x = 220.1 +/- 76.9 microg/kg i.m.) and atipamezole (x = 1,188.5 -/+ 328.1 microg/kg i.m.) compared with the adults (medetomidine, x = 131.1 +/- 19.5 microg/kg i.m.; atipamezole, x = 694.0 +/- 101.0 microg/kg i.m.). Juvenile alligators also required higher (statistically insignificant) doses of ketamine (x = 10.0 +/- 4.9 mg/kg i.m.) compared with the adult animals (x = 7.5 +/- 4.2 mg/kg i.m.). The differences in anesthesia induction times (juveniles, x = 19.6 +/- 8.5 min; adults, x = 26.6 +/- 17.4 min) and recovery times (juveniles, x = 35.4 +/- 22.1 min; adults, x = 37.9 +/- 20.2 min) were also not statistically significant. Anesthesia depth was judged by the loss of the righting, biting, corneal and blink, and front or rear toe-pinch withdrawal reflexes. Recovery in the animals was measured by the return of reflexes, open-mouthed hissing, and attempts to high-walk to the opposite end of the pen. Baseline heart rates (HRs) were significantly higher in the juvenile animals (x = 37 +/- 4 beats/min) compared with the adults (x = 24 +/- 5 bpm). However, RRs (juveniles, x = 8 +/- 2 breaths/min; adults, x = 8 +/- 2 breaths/min) and body temperatures (juveniles, x = 24.1 +/- 1.1 degrees C; adults, x = 25.2 +/- 1.2 degrees C) did not differ between the age groups. In both groups, significant HR decreases were recorded within 30-60 min after MK administration. Cardiac arrhythmias (second degree atrio-ventricular block and premature ventricular contractions) were seen in two animals but were not considered life-threatening. Total anesthesia times ranged from 61-250 min after i.m. injection. Although dosages were significantly different between the age groups, MK and atipamezole provided safe, effective, completely reversible anesthesia in alligators. Drug-dosage differences appear to be related to metabolic differences between the two size-classes, requiring more research into metabolic scaling as a method of calculating anesthetic dosages.

Partial antagonism of tiletamine-zolazepam anesthesia in cheetah.

This study evaluated partial antagonism of tiletamine-zolazepam (TZ) anesthesia in cheetahs (Acinonyx jubatus) and differences between two benzodiazepine antagonists, flumazenil and sarmazenil, in this species. Four cheetahs were anesthetized three times at an interval of 14 days with an average intramuscular dose of 4.2 mg/kg TZ. In trials 2 and 3 flumazenil at 0.031 mg/kg and sarmazenil at 0.1 mg/kg, respectively, were applied intramuscularly 30 min after initial TZ injection. There was a highly significant difference between the duration of TZ anesthesia with and without antagonist. Use of the antagonists significantly shortened duration and recovery and eliminated excitatory behavior during the recovery phase. No significant differences could be determined between the two antagonists. We recommend the use of sarmazenil and flumazenil to antagonize TZ anesthesia in cheetahs.

Tiletamine-zolazepam, ketamine, and xylazine anesthesia of captive cheetah (Acinonyx jubatus).

Thirty-two anesthetic episodes used a combination of tiletamine-zolezepam (50 mg/ml each), ketamine (80 mg/ml), and xylazine (20 mg/ml) at various dosages for routine diagnostic and minor surgical procedures in 13 captive cheetahs (Acinonyx jubatus). The mean dosage (0.023 +/- 0.003 ml/kg) provided rapid induction with a single i.m. injection along with safe predictable working time, good muscle relaxation, and analgesia. Yohimbine administration subsequently accelerated smooth and rapid recovery.

Medetomidine-ketamine in reindeer (Rangifer tarandus tarandus): effective immobilization by hand- and dart-administered injection.

Twelve reindeer (Rangifer tarandus tarandus) were immobilized by hand injection in indoor stalls with established optimal hand-injection doses of medetomidine-ketamine and then moved to outside paddocks where they were immobilized again with the same dose by dart. The reindeer in paddocks were immobilized a second time with a 50% higher dose, hereafter referred to as the optimal darting dose. Mean time to first sign of sedation was longer and mean induction time was significantly longer (55% and 79%, respectively) when the optimal hand-injection dose was dart injected versus hand injected. Mean time to first sign of sedation was not significantly shorter (although 21% shorter, numerically) but mean induction time was significantly shorter (30%) when animals were darted with the optimal darting dose versus darted with the optimal hand-injection dose. There were no significant differences in respiratory rate, rectal temperature, and relative arterial oxygen saturation in animals injected with different doses and by different routes. but there was a significantly lower heart rate in animals dart injected with the optimal darting dose versus dart injected with the optimal hand-injection dose. All animals responded at similar rates to atipamezole injection.

Use of medetomidine-zolazepam-tiletamine with and without atipamezole reversal to immobilize captive California sea lions.

From June 1998 to August 1999, 39 California sea lions (Zalophus californianus) were immobilized at a rehabilitation center in northern California (USA) using medetomidine plus zolazepam and tiletamine (MZT), alone and in combination with isoflurane, with atipamezole reversal. Animals were given 70 microg/kg medetomidine with 1 mg/kg of a 1:1 solution of tiletamine and zolazepam intramuscularly. Mean (+/-SD) time to maximal effect was 5+/-3 min. At the end of the procedure, animals were given 200 microg/kg atipamezole intramuscularly. Immobilization and recovery times were, respectively, 28+/-18 and 9+/-7 min for 15 animals maintained with MZT alone and 56+/-47 and 9+/-6 min for 18 animals intubated and maintained with isoflurane. One mortality occurred during anesthesia. Other disadvantages of the MZT combination included some prolonged ataxia, weakness and disorientation during recovery. However, the use of MZT resulted in faster induction and a more reliable plane of anesthesia that was reversible with atipamezole and safer than other previously used intramuscular agents. Physiological parameters including heart rate, respiratory rate, temperature, pulse oximeter saturation, and end-tidal carbon dioxide were monitored.

Chemical anesthesia of northern sea otters (Enhydra lutris): results of past field studies.

Between 1987 and 1997, we chemically immobilized 597 wild sea otters (Enhydra lutris) in Alaska for the collection of biological samples or for surgical instrumentation. One drug-related sea otter fatality occurred during this time. Fentanyl in combination with diazepam produced consistent, smooth inductions with minimal need for supplemental anesthetics during procedures lasting 30-40 min. Antagonism with naltrexone or naloxone was rapid and complete, although we observed narcotic recycling in sea otters treated with naloxone. For surgical procedures, we recommend a fentanyl target dose of 0.33 mg/kg of body mass and diazepam at 0.11 mg/kg. For nonsurgical biological sample collection procedures, we recommend fentanyl at 0.22 mg/kg and diazepam at 0.07 mg/kg. We advise the use of the opioid antagonist naltrexone at a ratio of 2:1 to the total fentanyl administered during processing.

Capture and immobilisation of aardvark (Orycteropus afer) using different drug combinations.

Nine aardvarks (Orycteropus afer) were captured in the southern Free State, South Africa, for the placement of abdominal radio transmitters. Five combinations of ketamine hydrochloride with xylazine hydrochloride, midazolam or medetomidine hydrochloride were used to induce anaesthesia. In some cases the level of anaesthesia was maintained with 1.5% halothane. A mixture of ketamine hydrochloride and medetomidine hydrochloride was found to be most effective. Atipamizole reversed the affects of medetomidine hydrochloride, resulting in a smooth and full recovery within 8 minutes. The immobilisation and subsequent anaesthesia of these animals on cold winter nights resulted in hypothermia, and keeping the animals warm was essential to the success of the procedures undertaken. Reversal of the sedative medetomidine hydrochloride proved to be important, because animals that were released before they were fully conscious took refuge in their burrows so that care was impossible.

Immobilization of wild kinkajous (Potos flavus) with medetomidine-ketamine and reversal by atipamezole.

As part of a wildlife rescue during the filling of a lake created by a hydroelectric dam (Petit Saut, French Guiana), 10 wild kinkajous (Potos flavus) were immobilized with medetomidine and ketamine for clinical examination and collection of biological samples. A mean (+/-SD) i.m. dose of 0.11+/-0.01 mg/kg medetomidine and 5.5+/-0.6 mg/kg ketamine rapidly induced complete immobilization (3.0+/-0.9 min) with good muscle relaxation and loss of corneal and pedal withdrawal reflexes. The duration and the quality of the anesthesia allowed procedures including minor surgery. Rectal temperature, heart and respiration rates, and relative oxyhemoglobin saturation (SpO2) were monitored at 5 min, 15 min, and 30 min after the medetomidine ketamine injection. Rectal temperature and heart rate significantly decreased during this time (P < 0.05). Low values of SpO2 (<90%) were recorded shortly after the injection. Hypoxemia partially resolved with time, confirmed by an increase in most SpO2 values. Atipamezole given i.m. at 5 mg/mg of medetomidine reversed the effects of the medetomidine in kinkajous. No adverse effects were observed during recovery. In group I, the antagonist was injected at 40.6+/-3.9 min. In group II, the animals showed signs of spontaneous recovery 37.9+/-6.9 min before antagonist injection at 52.2+/-6.1 min. Time from antagonist injection to ambulatory state was significantly shorter (P < 0.05) in group II (2.8+/-1.1 min) than in group I (6.9+/-1.2 min).

Observations on the use of medetomidine/ketamine and its reversal with atipamezole for chemical restraint in the mouse.

Ketamine and medetomidine produced chemical restraint for minor procedures in mice. Male mice required 50 mg/kg ketamine, 10 mg/kg medetomidine intraperitoneally (i.p.), and females a higher dose of ketamine (75 mg/kg i.p.). The onset of restraint effects, judged by loss of righting reflex, was more rapid in males than females. The effects were reversed using atipamezole (1-2.5 mg/kg). Recovery following administration of atipamezole was more rapid in males than females. We conclude that ketamine/medetomidine, followed by reversal with atipamezole, is an effective technique for chemical restraint in the mouse.

Reversible immobilization of free-ranging polar bears with medetomidine-zolazepam-tiletamine and atipamezole.

The objective of this study was to determine if the potent alpha 2 agonist, medetomidine, and its specific antagonist, atipamezole, could be effectively used to immobilize polar bears (Ursus maritimus). Specifically, our goal was to develop a drug combination containing medetomidine that addressed some of the problems such as prolonged recovery time, non-reversibility, and poor analgesia that have been identified with the currently preferred drug combination, zolazepamtiletamine (Telazol or Zoletil). During 1995 and 1996, 51 free-ranging polar bears along the western coast of Hudson Bay, Canada, were immobilized with a combination of medetomidine, zolazepam, and tiletamine (MZT). Immobilization with MZT was characterized by a short induction time, low volume, reliable and predictable immobilization and reversibility, adequate analgesia, and relative safety in handling for field personnel. Few adverse physiological effects were observed in any target animals with the exception of a single bear which convulsed and died shortly after it was reversed from anesthesia with atipamezole. We conclude that MZT is an effective drug combination for immobilizing polar bears. However, because of an unexplained mortality, further investigation of the physiological effects of MZT and atipamezole is warranted.

Safety considerations in the use of drug combinations during general anaesthesia.

The most commonly employed technique for providing general anaesthesia uses a balanced approach, where different drugs are used to reach specific desired endpoints. The variety of drugs used can result in a dozen or more different compounds being administered during a 'routine anaesthetic' procedure. Drug interactions are quite common and their clinical effects can be very significant. Clinically, general anaesthesia has 4 goals. These are: unconsciousness/amnesia; analgesia; muscle relaxation and maintenance of homeostasis. The anaesthesiologist tries to select only those drugs that permit a rapid onset of desirable operative conditions so that surgery can be performed properly and rapidly. Such drugs should also minimally disturb the patient's preoperative homeostatic maintenance, and maximise return to a desirable postanaesthetic functional state.