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.     

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.     

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.     

Anaesthesia with midazolam/medetomidine/fentanyl in chinchillas (Chinchilla lanigera) compared to anaesthesia with xylazine/ketamine and medetomidine/ketamine

We studied four different drug regimes for anaesthetic management in chinchillas and evaluated and compared their cardiovascular and respiratory effects. In this randomized, cross-over experimental study, seven adult chinchillas, five females, two males [515 +/- 70 (SD) g] were randomly assigned to one of the following groups: group 1 [midazolam, medetomidine and fentanyl (MMF), flumazenil, atipamezole and naloxone (FAN); MMF-FAN] received 1.0 mg/kg midazolam, 0.05 mg/kg medetomidine and 0.02 mg/kg fentanyl i.m., and for reversal 0.1 mg/kg flumazenil, 0.5 mg/kg atipamezole and 0.05 mg/kg naloxone s.c. after 45 min; group 2 (MMF) 1.0 mg/kg midazolam, 0.05 mg/kg medetomidine and 0.02 mg/kg fentanyl i.m.; group 3 [xylazine/ketamine (X/K)] 2.0 mg/kg xylazine and 40.0 mg/kg ketamine i.m.; and group 4 [medetomidine/ketamine (M/K)] 0.06 mg/kg medetomidine and 5.0 mg/kg ketamine i.m. Reflexes were judged to determine anaesthetic stages and planes. Anaesthesia with X/K and M/K was associated with a prolonged surgical tolerance and recovery period. By reversing MMF, recovery period was significantly shortened (5 +/- 1.3 min versus 40 +/- 10.3 min in MMF without FAN, 73 +/- 15.0 min in X/K, and 31 +/- 8.5 min in M/K). Without reversal, MMF produced anaesthesia lasting 109 +/- 16.3 min. All combinations decreased respiratory and heart rate but compared with X/K and M/K, respiratory and cardiovascular complications were less in the MMF groups. Focussing on the clinical relevance of the tested combinations, completely reversible anaesthesia showed two major advantages: anaesthesia can be antagonized in case of emergency and routinely shortens recovery. In small animals particularly these advantages lead to less complications and discomfort and thus often can be lifesaving. As all analgesic components (medetomidine and fentanyl) are reversed, postoperative analgesia should be provided before reversal of anaesthesia.     

Intramuscular anesthesia of bonito and Pacific mackerel with ketamine and medetomidine and reversal of anesthesia with atipamezole

OBJECTIVE: To determine anesthetic effects of ketamine and medetomidine in bonitos and mackerels and whether anesthesia could be reversed with atipamezole. DESIGN: Clinical trial. ANIMALS: 43 bonitos (Sarda chiliensis) and 47 Pacific mackerels (Scomber japonica). PROCEDURE: 28 bonitos were given doses of ketamine ranging from 1 to 8 mg/kg (0.5 to 3.6 mg/lb), i.m., and doses of medetomidine ranging from 0.2 to 1.6 mg/kg (0.1 to 0.7 mg/lb), i.m. (ratio of ketamine to medetomidine, 2.5:1 to 20:1). Doses of atipamezole equal to 1 or 5 times the dose of medetomidine were used. The remaining 15 bonitos were used to determine the anesthetic effects of ketamine at a dose of 4 mg/kg (1.8 mg/lb) and medetomidine at a dose of 0.4 mg/kg (0.2 mg/lb). The mackerels were given ketamine at doses ranging from 11 to 533 mg/kg (5 to 242 mg/lb) and medetomidine at doses ranging from 0.3 to 9.1 mg/kg (0.1 to 4.1 mg/lb; ratio of ketamine to medetomidine, 3:1 to 800:1). Doses of atipamezole equal to 5 times the dose of medetomidine were used. RESULTS: I.m. administration of ketamine at a dose of 4 mg/kg and medetomidine at a dose of 0.4 mg/kg in bonitos and ketamine at a dose of 53 to 228 mg/kg (24 to 104 mg/lb) and medetomidine at a dose of 0.6 to 4.2 mg/kg (0.3 to 1.9 mg/lb) in mackerels was safe and effective. For both species, administration of atipamezole at a dose 5 times the dose of medetomidine reversed the anesthetic effects. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that a combination of ketamine and medetomidine can safely be used for anesthesia of bonitos and mackerels and that anesthetic effects can be reversed with atipamezole.     

Comparison of three anaesthetic protocols in Bennett’s wallabies (Macropus rufogriseus)

ObjectiveInvestigate physiological and sedative/anaesthetic effects of xylazine, medetomidine or dexmedetomidine combined with ketamine in free-ranging Bennett's wallabies.Study designProspective clinical trial.AnimalsTwenty-six adult free-ranging Bennett's wallabies.MethodsAnimals were darted intramuscularly with one of three treatments: xylazine and ketamine, 2.0 and 15.0 mg kg^?1, respectively (XK): medetomidine and ketamine 0.1 and 5.0 mg kg^?1 (MK) and dexmedetomidine and ketamine 0.05 and 5.0 mg kg^?1 (DMK). Body weights were estimated. If the animal was still laterally recumbent after 45 minutes of anaesthesia, then an alpha-2 adrenoceptor antagonist, atipamezole, was administered (XK: 0.4 mg kg^?1, MK: 5 mg kg^?1, DMK: 2.5 mg kg^?1). Heart rate (HR) and respiratory rate (f_R) were recorded at 5-minute intervals and temperature at 10-minute intervals. Venous blood was taken 30 minutes after initial injection. Statistical analysis utilized anova. p < 0.05 was considered significant.ResultsAnimals became recumbent rapidly in all groups. XK animals had muscle twitches, responded to external stimuli, and three animals required additional dosing; this was not observed in the MK and DMK groups. HR (mean ± SD beats minute^?1) in XK (81 ± 4) was significantly higher than MK (74 ± 2) and DMK (67 ± 4). There were no differences in f_R, temperature, blood-gas and biochemical values between groups. More animals in MK (9/10) and DMK (5/6) needed antagonism of anaesthesia compared with XK (1/10). There were no adverse effects after anaesthesia.Conclusion and clinical relevanceCardio-respiratory effects were similar in all groups. There were fewer muscle twitches and reactions to external stimuli in MK and DMK. Duration of anaesthesia was shorter in XK; most animals in MK and DMK needed atipamezole to assist recovery. All three treatments provided satisfactory sedation/anaesthesia and are suitable for use in Bennett's wallabies.     

Medetomidine-ketamine-butorphanol anesthetic combinations in binturongs (Arctictis binturong).

The efficacy, safety, and reliability of two ketamine-medetomidine-butorphanol anesthetic combinations were evaluated in 34 adult binturongs (Arctictis binturong). The animals were randomly assigned to one of the two groups. On the basis of estimated body weights, group high ketamine (HK) received ketamine (8 mg/kg, i.m.), medetomidine (0.02 mg/kg, i.m.), and butorphanol (0.2 mg/kg, i.m.) combined in a single injection, and group low ketamine (LK) received ketamine (2 mg/kg, i.m.), medetomidine (0.04 mg/kg, i.m.), and butorphanol (0.2 mg/kg, i.m.). Cardiopulmonary parameters were measured for approximately 45 min; the animals were then administered atipamezole (5 mg/mg medetomidine, i.m.). Individual responses varied greatly to the anesthetic combinations, but similar numbers of animals in each group needed supplemental anesthetic agents (seven in group HK and six in group LK). Mean heart rates were higher in the LK group throughout anesthesia. Animals in both groups were mildly to moderately hypoxemic, but oxygenation improved in both groups following supplemental oxygen administration. Respiratory rates, arterial blood pressures, body temperatures, and end-tidal CO2 values were similar in both groups. Both protocols were effective; however, the LK combination is preferable because the mean recovery time was shorter.     

Clinical evaluation of three medetomidine--midazolam--ketamine combinations for neutering of ferrets (Mustela putorius furo)

33 ferrets (Mustela putorius furo, 11 females, 22 males, ASA I-II) were neutered in a combination anaesthesia with medetomidine, midazolam and ketamine. The animals were randomized into 3 groups. All animals received 20 microg/kg BW medetomidine and 0.5 mg/kg BW midazolam. The three groups differed regarding dosis and way of application of ketamine (IM10 = 10 mg/kg BW intramuscularly; IM07 = 7 mg/kg BW intramuscularly; SC10 = 10 mg/kg BW subcutaneously). After 30 minutes anaesthesia was partially antagonised with 100 microg/kg BW atipamezole i.m.. Sedation, muscle relaxation, analgesia, and overall anaesthetic impression were compared by a scoring protocol. Reactions to painful stimuli of clamping the spermatic cord or the ovarial ligament including the A. ovarica were judged, too. All animals lost their righting reflex and could be placed in dorsal recumbency. Induction and recovery time were significantly the shortest in study group IM10 with 1.73 +/- 0.3 and 9.73 +/- 4.6 min respectively. Recovery was significantly prolonged in group SC10 with 30.27 +/- 15.6 min. The MMK-anaesthesia with 10 mg/kg ketamine i.m. is very useful for neutering ferrets. Respiratory depression and bradycardia typically for medetomidine were seen in all three combinations, but quickly reversed after partial antagonisation. Induction and intubation, followed by inhalation anaesthesia, were possible with all three regimes.     

Sedative and cardiorespiratory effects of medetomidine, medetomidine-butorphanol, and medetomidine-ketamine in dogs

OBJECTIVE: To determine sedative and cardiorespiratory effects of i.m. administration of medetomidine alone and in combination with butorphanol or ketamine in dogs. DESIGN: Randomized, crossover study. ANIMALS: 6 healthy adult dogs. PROCEDURES: Dogs were given medetomidine alone (30 micrograms/kg [13.6 micrograms/lb] of body weight, i.m.), a combination of medetomidine (30 micrograms/kg, i.m.) and butorphanol (0.2 mg/kg [0.09 mg/lb], i.m.), or a combination of medetomidine (30 micrograms/kg, i.m.) and ketamine (3 mg/kg [1.36 mg/lb], i.m.). Treatments were administered in random order with a minimum of 1 week between treatments. Glycopyrrolate was given at the same time. Atipamezole (150 micrograms/kg [68 micrograms/lb], i.m.) was given 40 minutes after administration of medetomidine. RESULTS: All but 1 dog (given medetomidine alone) assumed lateral recumbency within 6 minutes after drug administration. Endotracheal intubation was significantly more difficult when dogs were given medetomidine alone than when given medetomidine and butorphanol. At all evaluation times, percentages of dogs with positive responses to tail clamping or to needle pricks in the cervical region, shoulder region, abdominal region, or hindquarters were not significantly different among drug treatments. The Paco2 was significantly higher and the arterial pH and Pao2 were significantly lower when dogs were given medetomidine and butorphanol or medetomidine and ketamine than when they were given medetomidine alone. Recovery quality following atipamezole administration was unsatisfactory in 1 dog when given medetomidine and ketamine. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that a combination of medetomidine with butorphanol or ketamine resulted in more reliable and uniform sedation in dogs than did medetomidine alone.     

Clinical effectiveness of atipamezole as a medetomidine antagonist in cats

The efficacy of atipamezole to reverse medetomidine induced effects in cats was investigated in a clinical study (n=160) including placebo. The atipamezole doses (intramuscularly) were two, four and six times (2X, 4X and 6X) the preceding medetomidine dose, which was 100 ug/kg body weight intramuscularly. Medetomidine was shown to produce moderate to deep sedation, recumbency and bradycardia in cat. Atipamezole was clearly able to reverse these effects of medetomidine. The median arousal time in the atipamezole dose groups was five minutes and walking time, 10 minutes, compared with more than 30 minutes in the placebo group. Heart rate was increased towards normal by atipamezole in a dose related manner. The clinical evaluation of the ability of atipamezole to reverse the effects of medetomidine was found to be ‘good’ in 82-5, 75 or 65 per cent of cases in dose groups 2X, 4X and 6X, respectively. The effect of atipamezole was evaluated as being ‘too potent’ in 2–5, 5 or 25 per cent of the cases in these respective groups. The incidence of side effects was negligible. In conclusion, atipamezole at the dose of two to four times the preceding dose of medetomidine seems to be an effective medetomidine antagonist for clinical use in cats.     

Medetomidine as a premedicant in dogs and its reversal by atipamezole

Medetomidine (10, 20, 40 μg/kg) was used as a premedicant before thiopentone, halothane and nitrous oxide anaesthesia in 60 dogs undergoing a variety of elective surgical and diagnostic procedures at the University of Liverpool Small Animal Hospital. The efficacy of the sedation produced by the three dose groups was evaluated using a sedation scoring system which is presented. Induction of anaesthesia was accomplished using 1–25 per cent thiopentone sodium administered slowly to effect. The mean dose of thiopentone required for intubation following 10 μ-g/kg medetomidine (group 1) was 6–9 mg/kg (SD ± 2–3 mg/kg), following 20 μ-g/kg medetomidine (group 2) was 4–5 mg/kg (SD ± 1–6 mg/kg) and following 40 μg/kg (group 3) was 2–4 mg/kg (SD ± 2–5 mg/kg). Induction of anaesthesia was generally smooth and significant apnoea (greater than 45 seconds) was not noted. Anaesthesia was maintained in all cases using halothane vapourised in a one part oxygen to two parts nitrous oxide mixture, delivered to the patient via a suitable non-breathing circuit (Magill, Bain or T Piece). At the conclusion of the procedure, atipamezole (50, 100, 200 μg/kg) was administered intramuscularly to half of the dogs in each group (10 dogs). Dogs receiving atipamezole recovered rapidly and smoothly to sternal recumbency, group 1 taking 8-5 minutes (SD ± 2–7 minutes), group 2 taking 11-8 minutes (SD ± 3–6 minutes), and group 3 taking 12-6 minutes (sd ± 4–5 minutes). When atipamezole was not administered a dose dependent increase in recumbency time occurred.     

Use of medetomidine for capture and restraint of cassowaries (Casuarius casuaris)

OBJECTIVE: To examine the use of medetomidine for the sedation of captive and wild cassowaries (Casuarius casuarius). DESIGN: Clinical evaluation after administration of medetomidine by IM injection. PROCEDURE: Nine captive and two wild birds were chemically restrained, with the drug being administered by dart to 10 birds and hand injected to one. Doses of 0.26 to 0.31 mg/kg IM provided light sedation sufficient to allow approach and limited handling. Doses of 0.38 to 0.54 mg/kg IM provided heavy sedation adequate for full clinical examination. Body weights were estimated in six birds and measured in five birds and ranged from 40 to 66 kg. Sternal recumbency occurred in six birds, three in each dose range. In nine birds sedation was reversed with atipamezole at a dose of 15 to 80 mg/kg IM, which produced a return to alertness in 40 to 139 min. Forceful sneezing occurred during recovery in three birds. CONCLUSION: Medetomidine is a safe and reliable alternative to manual restraint in cassowaries.     

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.     

Anaesthetic and cardiopulmonary effects of intramuscular morphine, medetomidine and ketamine administered to telemetered cats

The quality and duration of anaesthesia, cardiorespiratory effects and recovery characteristics of a morphine, medetomidine, ketamine (MMK) drug combination were determined in cats. Six healthy, adult female cats were administered 0.2 mg/kg morphine sulphate, 60 microg/kg medetomidine hydrochloride, and 5 mg/kg ketamine hydrochloride intramuscularly. Atipamezole was administered intramuscularly at 120 min after MMK administration. Time to lateral recumbency, intubation, extubation and sternal recumbency were recorded. Cardiorespiratory variables and response to a noxious stimulus were recorded before and at 3 min and 10 min increments after drug administration until sternal recumbency. The time to lateral recumbency and intubation were 1.9+/-1.2 and 4.3+/-1.2 min, respectively. Body temperature and haemoglobin saturation with oxygen remained unchanged compared to baseline values throughout anaesthesia. Respiratory rate, tidal volume, minute volume, heart rate, and blood pressure were significantly decreased during anaesthesia compared to baseline values. One cat met criteria for hypotension (systolic blood pressure <90 mmHg). End tidal carbon dioxide increased during anaesthesia compared to baseline values. All but one cat remained non-responsive to noxious stimuli from 3 to 120 min. Time to extubation and sternal recumbency following atipamezole were 2.9+/-1.1 and 4.7+/-1.0 min, respectively. MMK drug combination produced excellent short-term anaesthesia and analgesia with minimal cardiopulmonary depression. Anaesthesia lasted for at least 120 min in all but one cat and was effectively reversed by atipamezole.     

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.     

Evaluation of propofol and medetomidine-ketamine for short-term immobilization of Gulf of Mexico sturgeon (Acipenser oxyrinchus de soti).

Parenteral anesthetic protocols for short-term immobilization were evaluated in twenty 4-yr-old Gulf of Mexico sturgeon (Acipenser oxyrinchus de soti). An initial dose-response trial determined the efficacy of either propofol (3.5-7.5 mg/kg. i.v.) or combinations of medetomidine (0.03-0.07 mg/kg, i.m.)-ketamine (3-7 mg/kg, i.m.). A subsequent study evaluated the physiologic effects of propofol (6.5 mg/kg, i.v.)-induced anesthesia and anesthesia induced with a medetomidine (0.06 mg/kg, i.m.)-ketamine (6 mg/kg i.m.) combination. The effects of medetomidine were reversed at 30 min with atipamezole (0.30 mg/kg, i.m.). Both drug protocols provided adequate short-term immobilization for minor diagnostic procedures. Sturgeon receiving propofol were in a light plane of anesthesia within 5 min after drug administration, whereas only 30% of the medetomidine-ketamine group reached a light plane of anesthesia in the same time period. Both propofol and medetomidine-ketamine resulted in mild bradycardia and apparent respiratory depression, with propofol producing more profound effects. At the dosages used in this study, both propofol and the medetomidine-ketamine combination effectively induced a light plane of anesthesia. Induction times were shorter in the propofol group.     

Anesthesia of captive African wild dogs (Lycaon pictus) using a medetomidine-ketamine-atropine combination.

Seven captive male African wild dogs (Lycaon pictus) weighing 25-32 kg each, were anesthetized by i.m. injection via hand syringe with a combination of 1.5 mg/kg ketamine, 40 microg/kg medetomidine, and 0.05 mg/kg atropine. Following endotracheal intubation, each animal was connected to a bain closed-circuit system that delivered 1.5% isoflurane and 2 L/min oxygen. Atipamezole (0.1 mg/kg i.v.; 0.1 mg/kg i.m.) was given at the end of each procedure (60 min following injection of medetomidine/ketamine/atropine). Time to sternal recumbency was 5-8 min. Times to standing after atipamezole administration were 8-20 min. This anesthetic regimen was repeated on three separate occasions (September 2000, February 2002, and October 2002) on all males to perform electroejaculation procedures. Each procedure was <80 min from injection to standing. Dogs showed excellent muscle relaxation during the procedures. Arterial blood samples were collected at 10-min intervals for blood gases in one procedure (September 2000). Separate venous samples were taken from each dog during each procedure for hematology and biochemistry. These values were within the normal range for this species. Arterial hemoglobin oxygen saturation (SpO2) and heart rate (HR) were monitored continuously in addition to other anesthesia monitoring procedures (body temperature, respiratory rate [RR], capillary refill time, blink response, pupil position, deep pain perception reflex). All dogs maintained relatively stable SpO2 profiles during monitoring, with a mean (+/-SD) SpO2 of 92% +/-5.4%. All other physiological variables (HR, RR, body temperature, blood pressure) were within normal limits. Following each procedure, normal behavior was noted in all dogs. All the dogs were reunited into the pack at completion of their anesthetic procedures. An injectable medetomidine-ketamine-atropine combination with maintenance by gaseous isoflurane and oxygen provides an inexpensive, reliable anesthetic for captive African wild dogs.     

Effects of medetomidine and midazolam alone or in combination on the metabolic and neurohormonal responses in healthy cats

The purpose of this study was to investigate the effects of a medetomidine-midazolam combination on some neurohormonal and metabolic variables in healthy cats. Five cats were used repeatedly in each of 5 groups, which were injected intramuscularly with physiological saline solution (control), 0.5 mg/kg of midazolam, 40 microg/kg of medetomidine, 80 microg/kg of medetomidine, and 40 microg/kg of medetomidine plus 0.5 mg/kg of midazolam. Blood samples were taken 10 times over 24 h from a catheter introduced into the jugular vein. Plasma concentrations of glucose, insulin, glucagon, cortisol, nonesterified fatty acids (NEFAs), norepinephrine, and epinephrine were determined. In addition, the duration of lateral recumbency, rectal temperature, heart rate, and respiratory rate were examined. The combination of medetomidine and midazolam enhanced the duration of lateral recumbency and reduced the hyperglycemia induced by medetomidine alone. Recovery from hypoinsulinemia induced by the medetomidine-midazolam combination tended to be more rapid than when the same dose of medetomidine was used alone. The decrease in plasma norepinephrine levels induced by medetomidine alone was diminished by the addition of midazolam. Midazolam alone did not significantly change the plasma glucose, insulin, glucagon, cortisol, epinephrine, or NEFA concentration, but increased the norepinephrine concentration. This study revealed that the combination of medetomidine and midazolam produces minimal neurohormonal and metabolic changes when compared with medetomidine alone in cats.     

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.     

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.