Different Reactions of Zebra Finches and Bengalese Finches to a Three-Component Mixture of Anesthetics.

Kawai et al. (2011) recently introduced a mixture of three anesthetic agents (here called MMB) that has an effect similar to ketamine/xylazine in mice, which might allow more effective reaction to changes in the animal condition, as an antagonist is available, and which can be used without license for handling narcotic drugs. Using Kawai's study as a baseline, we tested whether this anesthesia and its antagonist can also be used in avian studies. In the present study, we used two species, the zebra finch and the Bengalese finch, of the avian family Estrildidae. In zebra finches, anesthesia effects similar to the use of ketamine/xylazine and to those obtained in mice can be reached by the use of MMB if a higher dose is applied. MMB leads to more variable anesthesia, but has the advantage of a longer time window of deep anesthesia. An antagonist to one component of MMB reduced the awaking time, but was not as effective as in mice. For Bengalese finches, MMB cannot be generally recommended because of difficult handling and high mortality rate when used without antagonist, but could be used for perfusions instead of pentobarbital.

Cardiovascular and sedation reversal effects of intramuscular administration of atipamezole in dogs treated with medetomidine hydrochloride with or without the peripheral α2-adrenoceptor antagonist vatinoxan hydrochloride.

OBJECTIVE: To investigate the cardiovascular and sedation reversal effects of IM administration of atipamezole (AA) in dogs treated with medetomidine hydrochloride (MED) or MED and vatinoxan (MK-467). ANIMALS: 8 purpose-bred, 2-year-old Beagles. PROCEDURES: A randomized, blinded, crossover study was performed in which each dog received 2 IM treatments at a ≥ 2-week interval as follows: injection of MED (20 µg/kg) or MED mixed with 400 µg of vatinoxan/kg (MEDVAT) 30 minutes before AA (100 µg/kg). Sedation score, heart rate, mean arterial and central venous blood pressures, and cardiac output were recorded before and at various time points (up to 90 minutes) after AA. Cardiac and systemic vascular resistance indices were calculated. Venous blood samples were collected at intervals until 210 minutes after AA for drug concentration analysis. RESULTS: Heart rate following MED administration was lower, compared with findings after MEDVAT administration, prior to and at ≥ 10 minutes after AA. Mean arterial blood pressure was lower with MEDVAT than with MED at 5 minutes after AA, when its nadir was detected. Overall, cardiac index was higher and systemic vascular resistance index lower, indicating better cardiovascular function, in MEDVAT-atipamezole-treated dogs. Plasma dexmedetomidine concentrations were lower and recoveries from sedation were faster and more complete after MEDVAT treatment with AA than after MED treatment with AA. CONCLUSIONS AND CLINICAL RELEVANCE: Atipamezole failed to restore heart rate and cardiac index in medetomidine-sedated dogs, and relapses into sedation were observed. Coadministration of vatinoxan with MED helped to maintain hemodynamic function and hastened the recovery from sedation after AA in dogs.

Effects of an anesthetic mixture of medetomidine, midazolam, and butorphanol and antagonism by atipamezole in rabbits.

Medetomidine (MED), midazolam (MID), and butorphanol (BUT) mixed anesthetic (MMB) has been used in laboratory animals since ketamine (KET) was designated as a narcotic in Japan in 2007. We previously reported that MMB produced anesthetic effects in mice and rats. We also demonstrated the efficacy of atipamezole (ATI), an antagonist of MED produced a quick recovery from anesthesia. Anesthetics have various anesthetic effects among different animal species. However, there is little information regarding its effects in rabbits. In the present study, we examined anesthetic effects of MMB compared to KET and xylazine mixed anesthetic (KX). We examined the antagonistic effects of ATI by intramuscular (IM) or intravenous (IV) injection in rabbits. We used the anesthetic score to measure surgical anesthetic duration and recovery time from anesthesia. During the experiments, we measured heart rate, respiratory rate, O2-saturation, and blood pressure. We found there were no significant differences in anesthetic duration and recovery time between MMB and KX. There were no significant differences in heart rate after administration of MMB or KX. Systolic blood pressure at 10 min after administration of MMB was higher than that of KX. The antagonistic effect of ATI by IV injection worked faster than that by IM injection. Overall, MMB is a useful drug that can induce similar anesthetic effects to KX and has an antagonist of ATI that makes rabbits quickly recover from anesthesia. These results may contribute to the welfare of laboratory animals, especially rabbits.

ECHOCARDIOGRAPHIC PARAMETERS IN EIGHT ADULT TIGERS ( PANTHERA TIGRIS) DURING TWO PHASES OF AN ANESTHETIC PROTOCOL.

Eight adult tigers ( Panthera tigris) underwent a complete echocardiographic examination following sedation with medetomidine, midazolam, and induction of general anesthesia using ketamine and isoflurane (phase 1). Atipamezole was used to antagonize medetomidine (phase 2) and a second echocardiographic examination was performed. Physiologic tricuspid and pulmonic regurgitations were common findings in the sample population and one tiger was excluded from final analyses due to the finding of a ventricular septal defect. Measurements and mean arterial pressure were assessed for statistically significant differences between the two examination phases as well as gender and weight. There was a statistically significant difference between interventricular septum thickness at end systole, ejection fraction, and mean arterial pressure between anesthetic phases while fractional shortening and left ventricular internal dimension at end-systole approached, but did not reach, statistical significance between phases. Weight was found to be a statistically significant predictor of stroke volume and left ventricular internal dimension at end-diastole. The echocardiographic measurements obtained during this study can be used as guidelines for future examinations in adult tigers. The effects of medetomidine on these measurements and systolic function should be taken into account when performing echocardiograms and monitoring anesthetic events.

Sedative effect of intramuscular medetomidine with and without vatinoxan (MK-467), and its reversal with atipamezole in sheep.

OBJECTIVE: To evaluate the effect of the peripherally acting α2-adrenoceptor antagonist vatinoxan (MK-467) on the sedative properties of medetomidine (MED) when injected intramuscularly (IM) in the same syringe and on reversal of this sedation with atipamezole in sheep. STUDY DESIGN: Randomized, blinded, crossover experimental trial. ANIMALS: Eight healthy adult female sheep. METHODS: Sheep received MED (30 µg kg-1 IM) alone or combined in the same syringe with vatinoxan (300 µg kg-1 IM, MED+VAT) with a 2 week washout period. Atipamezole (150 µg kg-1 IM) was administered 30 minutes later for reversal. Sedation was assessed using two sedation scores, a visual analog score and a descriptive scale before treatments (T0) and at intervals up to 5 hours thereafter. Pulse rate (PR) was counted at T0 and at 30 (T30) and 90 (T90) minutes. Rectal temperature was measured at T0 and T90 postinjection. Plasma samples were analyzed for drug concentrations at T30 and T90. RESULTS: The first signs of sedation were seen significantly earlier after MED+VAT (4.6 ± 1.7 minutes versus 9.4 ± 2.6 minutes after MED) and the sedation scores were significantly higher after MED+VAT than MED. All animals laid with head down 10.0 ± 3.4 minutes after MED+VAT, whereas three MED animals did not become recumbent before atipamezole was administered. The plasma concentrations of dexmedetomidine were significantly higher at T30 (2.47 ± 0.2 ng mL-1) and significantly lower at T90 (1.23 ± 0.3 ng mL-1) with MED+VAT than with MED (1.19 ± 0.8 and 1.83 ± 0.4 ng mL-1, respectively). While no significant differences were observed between treatments in PR at T30, PR at T90 was significantly higher with MED+VAT than with MED. CONCLUSIONS AND CLINICAL RELEVANCE: When administered IM in the same syringe, vatinoxan hastened and intensified the initial sedative effects of MED and enhanced the sedation reversal by atipamezole.

Propofol-medetomidine-ketamine total intravenous anaesthesia in thiafentanil-medetomidine-immobilized impala (Aepyceros melampus).

OBJECTIVE: To characterize a propofol-medetomidine-ketamine total intravenous anaesthetic in impala (Aepyceros melampus). STUDY DESIGN: Prospective clinical study. ANIMALS: Ten adult female impala. MATERIALS AND METHODS: Impala were immobilized at 1253 m above sea level with 2.0 mg thiafentanil and 2.2 mg medetomidine via projectile darts. Propofol was given to effect (0.5 mg kg-1 boluses) to allow endotracheal intubation, following which oxygen was supplemented at 2 L minute-1. Anaesthesia was maintained with a constant-rate infusion of medetomidine and ketamine at 5 µg kg-1 hour-1 and 1.5 mg kg-1 hour-1, respectively, and propofol to effect (initially 0.2 mg kg-1 minute-1) for 120 minutes. The propofol infusion was titrated according to reaction to nociceptive stimuli every 15 minutes. Cardiopulmonary parameters were monitored continuously and arterial blood gas samples were analysed intermittently. After 120 minutes' maintenance, the thiafentanil and medetomidine were antagonized using naltrexone (10:1 thiafentanil) and atipamezole (5:1 medetomidine), respectively. RESULTS: All impala were successfully immobilized. The median dose [interquartile range (IQR)] of propofol required for intubation was 2.7 (1.9-3.3) mg kg-1. The propofol-medetomidine-ketamine combination abolished voluntary movement and ensured anaesthesia for the 120 minute period. Propofol titration showed a generally downward trend. Median (IQR) heart rate [57 (53-61) beats minute-1], respiratory rate [10 (9-12) breaths minute-1] and mean arterial blood pressure [101 (98-106) mmHg] were well maintained. Arterial blood gas analysis indicated hypoxaemia, hyper- capnia and acidaemia. Butorphanol (0.12 mg kg-1) was an essential rescue drug to counteract thiafentanil-induced respiratory depression. All impala regurgitated frequently during the maintenance period. Recovery was calm and rapid in all animals. Median (IQR) time to standing from antagonist administration was 4.4 (3.2-5.6) minutes. CONCLUSIONS AND CLINICAL RELEVANCE: A propofol-medetomidine-ketamine combination could provide adequate anaesthesia for invasive procedures in impala. The propofol infusion should begin at 0.2 mg kg-1 minute-1 and be titrated to clinical effect. Oxygen supplementation and airway protection with a cuffed endotracheal tube are essential.

Injection anaesthesia with fentanyl-midazolam-medetomidine in adult female mice: importance of antagonization and perioperative care.

Injection anaesthesia is commonly used in laboratory mice; however, a disadvantage is that post-anaesthesia recovery phases are long. Here, we investigated the potential for shortening the recovery phase after injection anaesthesia with fentanyl-midazolam-medetomidine by antagonization with naloxone-flumazenil-atipamezole. In order to monitor side-effects, the depth of anaesthesia, heart rate (HR), core body temperature (BT) and concentration of blood gases, as well as reflex responses, were assessed during a 50 min anaesthesia. Mice were allowed to recover from the anaesthesia in their home cages either with or without antagonization, while HR, core BT and spontaneous home cage behaviours were recorded for 24 h. Mice lost righting reflex at 330 ± 47 s after intraperitoneal injection of fentanyl-midazolam-medetomidine. During anaesthesia, HR averaged 225 ± 23 beats/min, respiratory rate and core BT reached steady state at 131 ± 15 breaths/min and 34.3 ± 0.25℃, respectively. Positive pedal withdrawal reflex, movement triggered by tail pinch and by toe pinch, still occurred in 25%, 31.2% and 100% of animals, respectively. Arterial blood gas analysis revealed acidosis, hypoxia, hypercapnia and a marked increase in glucose concentration. After anaesthesia reversal by injection with naloxone-flumazenil-atipamezole, animals regained consciousness after 110 ± 18 s and swiftly returned to physiological baseline values, yet they displayed diminished levels of locomotion and disrupted circadian rhythm. Without antagonization, mice showed marked hypothermia (22 ± 1.9℃) and bradycardia (119 ± 69 beats/min) for several hours. Fentanyl-midazolam-medetomidine provided reliable anaesthesia in mice with reasonable intra-anaesthetic side-effects. Post-anaesthetic period and related adverse effects were both reduced substantially by antagonization with naloxone-flumazenil-atipamezole.

Effects of MK-467 on the antinociceptive and sedative actions and pharmacokinetics of medetomidine in dogs.

We investigated the influence of the peripherally acting α2 -adrenoceptor antagonist MK-467 on the sedative and antinociceptive actions and plasma drug concentrations of medetomidine, an α2 -adrenoceptor agonist that is used in veterinary medicine as a sedative and analgesic agent. Eight healthy beagle dogs received intravenous medetomidine (10 µg/kg) or medetomidine with MK-467 (250 µg/kg) in a randomized crossover design. A standardized nociceptive pressure stimulus was applied to a nail bed of a hindlimb. Times for withdrawal of the limb and for head lift were measured, and sedation was scored. EEG data were collected prior to and after stimulation. Plasma drug concentrations were measured. Co-administration of MK-467 significantly attenuated medetomidine analgesia, as assessed with limb withdrawal, and also shortened the duration of sedation. The apparent plasma clearance of both enantiomers of medetomidine, dexmedetomidine and levomedetomidine, was more than doubled in the presence of MK-467. Antagonism by MK-467 of medetomidine-evoked vasoconstriction is seen as the mechanism behind this pharmacokinetic drug interaction. Thus, MK-467 attenuated the antinociceptive and sedative effects of medetomidine. This can probably be explained by increased clearance and decreased concentrations of dexmedetomidine in plasma after co-administration of MK-467 with racemic medetomidine.

Effects of an anesthetic mixture of medetomidine, midazolam, and butorphanol in rats-strain difference and antagonism by atipamezole.

An anesthetic mixture of medetomidine (MED), midazolam (MID), and butorphanol (BUT) has been used in laboratory animals. We previously reported that this anesthetic mixture produced closely similar anesthetic effects in BALB/c and C57BL/6J strains. We also demonstrated the efficacy of atipamezole (ATI), an antagonist of MED that produced quick recovery from anesthesia in mice. Anesthetics have various anesthetic effects among animal strains. However, the differences in the effects of anesthetic mixtures in rats are unclear. In the present study, we first examined effects of the abovementioned anesthetic mixture using three different rat strains: Wistar (WST), Sprague-Dawley (SD), and Fischer 344 (F344). Second, we examined how different dosages and optimum injection timing of ATI affected recovery from anesthesia in rats. We used the anesthetic score to measure anesthetic duration and a pulse oximeter to monitor vital signs. We found no significant differences in anesthetic duration among the three different strains. However, recovery from anesthesia in the SD strain took significantly longer than in the other strains. The antagonistic effects of ATI (0.15 mg/kg and 0.75 mg/kg) were equivalent when administered at 30 min after anesthetic mixture administration. The antagonistic effects of ATI 0.75 mg/kg were stronger than those of ATI 0.15 mg/kg at 10 min after anesthetic mixture administration. This anesthetic mixture is a useful drug that can induce similar anesthetic effects in three different strains and has an antagonist, ATI, that makes rats quickly recover from anesthesia. These results may contribute to the welfare of laboratory animals.

Anesthetic effects of a three-drugs mixture--comparison of administrative routes and antagonistic effects of atipamezole in mice.

The anesthetic mixture of medetomidine (MED), midazolam (MID) and butorphanol (BUT) produced anesthetic duration of around 40 minutes (min) in ICR mice. We reported that this anesthetic mixture produced almost the same anesthetic effects in both male and female BALB/c and C57BL/6J strains. Intraperitoneal (IP) administration of drugs has been widely used in mice. However, various injectable routes of the anesthetic mixture may cause different anesthetic effects. First, we examined effects of the anesthetic mixture by subcutaneous (SC) and intravenous (IV) injection compared to IP injection. After injection of the anesthetic mixture, administration of atipamezole (ATI) induced mice recovery from anesthesia. Secondly, we examined how different dosage and optimum injection timing of ATI affected mice recovery from anesthesia. We used an anesthetic score to measure anesthetic duration and a pulse oximeter to monitor vital signs under anesthesia. Usually, drugs from SC injection work more weakly than IP or IV injection. However, we found no significant differences of anesthetic duration among the three different injection routes. Antagonistic effects of ATI (0.3 mg/kg and 1.5 mg/kg) worked equally when administered at 30 min after injection of the anesthetic mixture. Antagonistic effects of ATI (1.5 mg/kg) were stronger than ATI (0.3 mg/kg) at 10 min after injection of the anesthetic mixture. The anesthetic mixture is a useful drug to induce nearly the same anesthetic effects by different injection routes and has an antagonist of ATI which helps mice quickly recover from anesthesia. These results may contribute to the welfare of laboratory animals.

Haemodynamic interactions of medetomidine and the peripheral alpha-2 antagonist MK-467 during step infusions in isoflurane-anaesthetised dogs.

The haemodynamic interactions of a step infusion with medetomidine (MED) and the peripherally acting alpha-2 antagonist MK-467 (MK) were compared with MED infused alone in isoflurane-anaesthetised dogs. Eight purposely-bred Beagles were used in a randomised crossover study. Anaesthesia was induced with propofol intravenously (IV) and maintained with isoflurane in oxygen. Dogs received 1.25 µg/kg MED as a 1 min loading dose IV, along with a step-down MED infusion at rates of 8.0 µg/kg/h (step 1: 0-20 min), 5.5 µg/kg/h (step 2: 20-40 min) and 4.0 µg/kg/h (step 3: 40-95 min). Five minutes after starting the MED infusion, the dogs received MK-467 in a step-up infusion at rates of 100 µg/kg/h (step 1: 5-35 min), 200 µg/kg/h (step 2: 35-65 min) and 500 µg/kg/h (step 3: 65-95 min). Heart rate (HR), systolic (SAP) and mean arterial (MAP) blood pressures and arteriovenous oxygen content differences (a-vO2 diff) were calculated. Plasma drug concentrations were analysed. Repeated-measures general linear mixed models with Bonferroni correction were used for statistical analyses. MED infusion alone increased SAP maximally by 24.9%, MAP by 34.7% and a-vO2 diff by 222.5%, and reduced HR by 32.3%, but these changes were significantly attenuated by MK-467. Most MED effects returned to baseline during step 2 of MK-467 infusion and step 3 of MED infusion (MED/MK-467 ratio 1:18 to 1:50). Plasma concentrations of MED tended to be lower with the addition of MK-467. The use of step infusions helped to narrow down the therapeutic range for the MED/MK-467 infusion dose ratio during isoflurane anaesthesia in dogs.

Antagonistic effects of atipamezole, yohimbine and prazosin on medetomidine-induced diuresis in healthy cats.

This study aimed to investigate and compare the antagonistic effects of atipamezole, yohimbine and prazosin on medetomidine-induced diuresis in healthy cats. Five cats were repeatedly used in each of the 9 groups. One group was not medicated. Cats in the other groups received 40 µg/kg medetomidine intramuscularly and saline (as the control), 160 µg/kg prazosin, or 40, 160 or 480 µg/kg atipamezole or yohimbine intravenously 0.5 hr later. Volume, pH and specific gravity of urine; plasma arginine vasopressin (AVP) level; and creatinine, osmolality and electrolyte levels in both urine and plasma were measured. Both atipamezole and yohimbine, but not prazosin, antagonized medetomidine-induced diuresis. The antidiuretic effect of atipamezole was more potent than that of yohimbine, but was not dose dependent, in contrast to the effect of yohimbine at the tested doses. Both atipamezole and yohimbine reversed medetomidine-induced decreases in both urine specific gravity and osmolality and increases in plasma osmolality and free-water clearance. Antidiuresis of either atipamezole or yohimbine was not related to the area under the curve for AVP level, although the highest dose of both atipamezole and yohimbine initially and temporarily increased plasma AVP levels, suggesting that this may partly influence the antidiuretic effects of both agents. The diuretic effect of medetomidine in cats may be mediated by α2-adrenoceptors, but not α1-adrenoceptors. Atipamezole and yohimbine can be used as antagonistic agents against medetomidine-induced diuresis in healthy cats.

Evaluation of medetomidine-ketamine and atipamezole for reversible anesthesia of free-ranging gray wolves (Canis lupus).

Twenty-eight anesthetic events were carried out on 24 free-ranging Scandinavian gray wolves (Canis lupus) by darting from a helicopter with 5 mg medetomidine and 250 mg ketamine during winter in 2002 and 2003. Mean±SD doses were 0.162±0.008 mg medetomidine/kg and 8.1±0.4 mg ketamine/kg in juveniles (7-10 mo old) and 0.110±0.014 mg medetomidine/kg and 5.7±0.5 mg ketamine/kg in adults (>19 mo old). Mean±SD induction time was shorter (P<0.01) in juveniles (2.3±0.8 min) than in adults (4.1±0.6 min). In 26 cases, the animals were completely immobilized after one dart. Muscle relaxation was good, palpebral reflexes were present, and there were no reactions to handling or minor painful stimuli. Mild to severe hyperthermia was detected in 14/28 anesthetic events. Atipamezole (5 mg per mg medetomidine) was injected intramuscularly for reversal 98±28 and 94±40 min after darting in juveniles and adults, respectively. Mean±SD time from administration of atipamezole to coordinated walking was 38±20 min in juveniles and 41±21 min in adults. Recovery was uneventful in 25 anesthetic events, although vomiting was observed in five animals. One adult that did not respond to atipamezole was given intravenous fluids and was fully recovered 8 hr after darting. Two animals died 7-9 hr after capture, despite intensive care. Both mortalities were attributed to shock and circulatory collapse following stress-induced hyperthermia. Although effective, this combination cannot be recommended for darting free-ranging wolves from helicopter at the doses presented here because of the severe hyperthermia seen in several wolves, two deaths, and prolonged recovery in one individual.

Preliminary studies of chemical immobilization of captive juvenile estuarine (Crocodylus porosus) and Australian freshwater (C. johnstoni) crocodiles with medetomidine and reversal with atipamezole.

OBJECTIVE: To establish a safe, reliable and reversible immobilization protocol for captive juvenile crocodiles. STUDY DESIGN: Prospective, randomized, clinical study. ANIMALS: Thirty male estuarine crocodiles (body mass 1-12.1 kg) and 10 male Australian freshwater crocodiles (body mass 4.1-12.8 kg). METHODS: An optimized dose of medetomidine (0.5 mg kg(-1)) was administered intramuscularly (IM) into the tail (Group 1; n = 5), pelvic limb (Group 2; n = 5) and thoracic limb (Groups 3 and 4; n = 5 in each group) of estuarine crocodiles weighing 3-12.1 kg. Their heart and respiratory rates and degree of immobilization were monitored every 15 minutes until recovery and daily thereafter for 3 subsequent days. In Group 4 (n = 5), medetomidine was antagonized with an optimized dose of atipamezole (2.5 mg kg(-1)) given IM into the thoracic limb and time to recovery recorded. The effects of increasing doses of medetomidine given IM in the thoracic limb (n = 4) and intravenously (n = 6) were determined in 1-2 kg estuarine crocodiles. Australian freshwater crocodiles (4.1-12.8 kg) were administered medetomidine IM into the thoracic limb in divided doses at 0.5 mg kg(-1) (n = 5) and 0.75 mg kg(-1) (n = 5) and similarly monitored. RESULTS: Immobilization was achieved only in the estuarine crocodiles >3 kg and when medetomidine was administered into the thoracic limb. Immobilization was achieved within 30 minutes and the duration of immobilization lasted approximately 90 minutes. Immobilization in estuarine crocodiles was readily reversed with atipamezole. A dose of 0.75 g kg(-1) was required to immobilize Australian freshwater crocodiles and the onset of immobilization was longer and the duration shorter than seen in the estuarine crocodiles. The heart and respiratory rates of all immobilized animals decreased significantly and arterial blood pressure became undetectable in the animals in which it was measured. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine administered in the thoracic limb of captive estuarine and Australian freshwater crocodiles, ranging from 3 to 12.8 kg, provides a predictable onset and duration of immobilization sufficient for physical examination, sample collection, short minor procedures and translocation of the animals. Atipamezole administered in the thoracic limb results in complete reversal of the effects of medetomidine in the estuarine crocodile and a rapid return to normal behaviour.

Field immobilization of feral 'Judas' donkeys (Equus asinus) by remote injection of medetomidine and ketamine and antagonism with atipamezole.

The Judas technique is a method used for landscape control of feral donkeys (Equus asinus) in northern Australia. Central to the success of any Judas program is the safe, efficient, and humane attachment of the telemetry device. For feral donkeys, this involves the use of field immobilization. We examine the replacement of the current chemical capture agent, succinylcholine, with contemporary immobilization agents to achieve positive animal welfare outcomes. A combination of medetomidine and ketamine delivered by remote injection from a helicopter was used to capture 14 free-ranging feral donkeys for the fitting of telemetry collars in Western Australia in November 2010. Dose rates of 0.14 mg/kg medetomidine and 4.1 mg/kg ketamine were appropriate to immobilize animals in 9 min (± SD = 3). Mean recovery time (total time in recumbency) was 21 min (± 14). All animals recovered uneventfully after being administered atipamezole, a specific antagonist of medetomidine, intramuscularly at 0.35 mg/kg. Physiologic parameters were recorded during recumbency, with environment-related hyperthermia being the only abnormality recognized. No significant complications were encountered, and this drug combination represents an efficient approach to capturing wild donkeys. This new method allows a rapid, safe, cost-effective approach to the immobilization of feral donkeys for use as Judas animals. This drug combination will replace the relatively inhumane succinylcholine for the field immobilization of feral donkeys.

Chemical immobilization of raccoons (Procyon lotor) with ketamine-medetomidine mixture and reversal with atipamezole.

Safe and reliable capture techniques for wild animals are important for ecologic studies and management operations. We assessed the efficiency of ketamine-medetomidine (K:M) injection and reversal with atipamezole. We anesthetized 67 raccoons (Procyon lotor; 34 males, 33 females) 103 times (individuals captured between one and five times) from April 2009-October 2010 in Mont-Orford Provincial Park, Quebec, Canada. We administered a 1:1 mixture by volume of ketamine and medetomidine by intramuscular injection. Mean (±SD) induction times for males and females were 6.1±2.8 and 6.6±3.7 min, respectively. Mean induction time was 2 min longer for juveniles than for adults (7.8±3.9 and 5.8±2.9 min, respectively) and longer in autumn than in spring for adults (7.7±3.8 and 5.4±2.9 min, respectively). Recovery time after administration of atipamezole was 9.6±3.8 and 8.4±4.4 min for males and females, respectively. Recovery time was longer in spring than in autumn (10.2±4 and 7.4±3.8 min, respectively) for adults. Induction time increased by 166% after five captures of the same individual. Immobilization did not affect body mass, adult survival, or female reproductive success. We suggest the K:M mixture used is a safe and reliable method for anesthetizing raccoons in field conditions.

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.

Effects of early atipamezole reversal of medetomidine-ketamine anesthesia in mice.

Rodents are often anesthetized by using ketamine and medetomidine, with reversal by atipamezole. Methods vary for times of administration of the atipamezole, and literature is lacking regarding appropriate reversal time. We investigated the recovery of mice reversed with atipamezole 10 min (early) or 40 min (late) after induction of anesthesia. Time to regain pinch-reflex or righting reflex did not differ between the 2 reversal points, but time to walking was significantly greater in mice that underwent early reversal with atipamezole. This delay was not mitigated by administration of atropine as part of the anesthetic regimen. Inclusion of acetylpromazine in the anesthetic regimen shortened the time needed to reach a surgical plane of anesthesia but also prolonged recovery times as determined by righting reflex and time to walking.

Effects of medetomidine-midazolam-fentanyl IV bolus injections and its reversal by specific antagonists on cardiovascular function in rabbits.

The objective of this study was to investigate the short-term cardiovascular effects of intravenous (IV) medetomidine-midazolam-fentanyl (MMF) injections in the rabbit using vascular ultrasonography and echocardiography.Anesthesia with MMF was induced intramuscularly (IM) in 8 female New Zealand White rabbits before 3 defined bolus injections of MMF were given IV. Before and for 10 min after each MMF injection the following vascular variables [at the left common carotid artery (ACC) after the first injection and at the abdominal aorta (AA) after the second injection]: vessel diameter (D), peak systolic, minimum diastolic, end-diastolic and average blood flow velocities (psBFV, mdBFV, edBFV, Vave), average volumetric flow (VFave), resistance index (RI) and pulsatility index (PI) and other clinical variables: mean arterial pressure (MAP), heart rate (HR), peripheral arterial oxygen saturation and end-tidal CO2 were recorded. Echocardiography was used after the third injection to investigate changes in cardiac parameters. Additionally, hemodynamic effects were observed at the ACC after complete subcutaneous antagonism of anesthesia by atipamezole-flumazenil-naloxone (AFN) until recovery of the animals.Medetomidine-midazolam-fentanyl IV caused a significant decrease of blood flow velocity in both investigated vessels which was associated with a significant decrease of HR and cardiac performance indicated by the decrease of FS and average volumetric blood flow. Mean arterial pressure significantly increased after each MMF injection; whereas, it significantly decreased after AFN injection. Therefore, MMF and AFN should be carefully used in rabbits and may not be suitable in patients with ventricular dysfunction.