Medetomidine/ketamine sedation in calves and its reversal with atipamezole

Atipamezole was used to reverse the sedation induced in calves by medetomidine/ketamine. Thirteen claves subjected to umbilical surgery received medetomidine 20 μg/kg bodyweight (bwt) and ketamine 0.5 mg/kg bwt intravenously (iv) from a mixture of the drugs in one syringe. Atipamezole was given at doses of 20 to 60 μg/kg iv and intramuscularly (im) to the calves at the end of the operation. Following the administration of medetomidine and ketamine, PaCO₂ increased whereas pH, PaO₂ and heart rate decreased. Reversing the effects of medetomidine with atipamezole did not cause undesirable effects; recovery was rapid and smooth, most of the animals reached a standing position within 1 to 3 mins after the atipamezole injection.     

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.     

Medetomidine immobilisation and atipamezole reversal in large estuarine crocodiles (Crocodylus porosus) using metabolically scaled dosages

Background Restraint of large estuarine crocodiles is potentially dangerous. Neuromuscular blockers and other immobilising drugs have been used with variable results. Medetomidine has been reported as a reliable, repeatable and reversible immobilisation agent in small estuarine crocodilians. Methods and Results Two wild and two farmed male animals, between 3.05 and 4.6 m long, were hand‐injected into a triceps muscle with a metabolically scaled medetomidine dosage. Immobilisation occurred within 30 min. At the conclusion of the procedures, 70 min after medetomidine administration, three animals were injected with atipamezole IM into the opposite triceps muscle at a dosage based on body surface area. Reversal occurred within 5 min. The fourth animal was intubated prior to reversal of medetomidine and maintained on isoflurane anaesthesia for a gastrotomy. All animals were monitored closely post recovery and then regularly for at least 1 week. Conclusions Medetomidine at a metabolically scaled dosage delivered IM into the forelimb was effective for immobilising large estuarine crocodiles for at least 40 min. Atipamezole administered at a dosage calculated as a function of surface area effectively reversed this immobilisation.     

Cardiovascular effects of medetomidine-ketamine anaesthesia in sheep, with and without 100% oxygen, and its reversal with atipamezole.

The cardiovascular effects of intravenously (iv) administered medetomidine 20 μg/kg bodyweight (bwt) and ketamine (2 mg/kgbwt), with and without 100% inspired oxygen, were investigated in six domestic sheep. A second dose of medetomidine and ketamine was administered iv, at dose 10 μg/kg bwt and 1 mg/kg bwt respectively, 25 minutes after the initial injection. Heart rate, PaO₂ pH and haemoglobin saturation decreased whereas PaCO₂ and base excess increased post-injection. Transient hypertension and an increase in respiration rate were evident within the first 10 minutes of anaesthesia. Significant hypoxaemia (P<0.01) developed in sheep breathing room air. Inspired 100% oxygen improved PaO₂ (but the difference was not significant), and improved haemoglobin saturation significantly (P<0.05), however, this effect varied between individuals. One sheep breathing room air suffered a cardiac arrest immediately post-injection and had to be resuscitated. Atipamezole 125 μg/kg given intramuscularly 45 minutes after the initial injection rapidly reversed the effects of medetomidine. Recovery times did not significantly differ although time to extubation and standing tended to be longer in sheep breathing room air compared to the sheep breathing 100% oxygen. The quality of the recovery did not differ.     

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.     

Clinical observations on medetomidine/ketamine anaesthesia in sheep and its reversal by atipamezole

Medetomidine (25 μg/kg) and ketamine (1mg/kg) were administered intramuscularly to anaesthetise 13 sheep for experimental oral surgery. Anaesthesia was characterised by good muscle relaxation and tachypnoea. Heart rates were not significantly different from those recorded before administration of the anaesthetic agents. Spontaneous recovery from anaesthesia was allowed in five sheep. In eight sheep atipamezole, at a total dose of 125 μg/kg, divided and administered both intravenously and intramuscularly, hastened return to full awareness.     

Xylazine-induced sedation in axis deer (Axis axis) and its reversal by atipamezole

Eight free-ranging axis deer (Axis axis) were captured in drive nets and injected with xylazine (3.4±0.1 mg/kg; mean ±SEM) intramuscularly using a hand-held syringe. Xylazine induced complete immobilization and sedation in three animals, heavy sedation in three, and moderate sedation in two. The mean induction time was 10.4±1.0 min. The mean rectal temperature, heart and respiratory rates of immobilized animals were 39.2±0.4°C, 75.5±6.5 beats/min and 62.1±4.2 breaths/min, respectively.All the animals were given atipamezole intravenously for reversal. The mean time from injection of xylazine to administration of atipamezole was 37.8±4.6 min. A dose ratio (w/w) for xylazine:atipamezole-HCl of 10:1 was used. The mean time from injection of atipamezole to mobility was 2.41±0.58 min.Atipamezole given intravenously effectively antagonized xylazine-induced sedation in axis deer. Only one animal showed signs of overalertness after reversal and no cases of resedation were observed.Abbreviations i.m. intramuscular(ly) - i.v. intravenous(ly) - SEM standard error of the mean     

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.     

Long-term anaesthesia with propofol and alfentanil in the dog and its partial reversal with nalbuphine

Prolonged surgical anaesthesia in the dog was induced with propofol (6.5 ± 1.3 mg/kg) followed by alfentanil (25.5 ± 5 μg/kg) (mean ± 1 sd) and maintained with a continuous infusion of propofol (0.14 to 0.18 mg/kg/min) and alfentanil (2 to 3 μg/kg/min). Neuromuscular blockade was produced with vecuronium (0.1 mg/kg). After induction of anaesthesia with propofol, administration of alfentanil to dogs which had received no pre-anaesthetic medication produced cardiac arrest and apnoea. Administration of atropine intravenously immediately prior to alfentanil prevented these cardiac depressant effects. The cardiac depressant effect of alfentanil was not as severe in a second group of dogs in which anaesthesia was induced with thiopentone. After commencing the continuous infusion anaesthetic regime and establishment of IPPV, blood pressure and heart rate remained stable during the remaining 4 to 6 h period of anaesthesia. Recovery from anaesthesia was smooth and uneventful. The depressant effects of alfentanil on respiration and on consciousness were reversed rapidly by administration of nalbuphine (10 mg total dose). The smooth recovery and the integration of anaesthesia and post operative analgesia attained by the reversal of alfentanil with nalbuphine make this an attractive anaesthetic regime for major surgery in dogs, provided that facilities for IPPV are available.     

Medetomidine and dexmedetomidine: a review of cardiovascular effects and antinociceptive properties in the dog

Alpha(2)-adrenoreceptor agonists (alpha(2)-agonists) are commonly used in small animal anaesthesia for their potent sedative and analgesic properties, although concerns about their cardiovascular effects have prevented their full adoption into veterinary practice. Research into alpha(2) adrenoreceptor agonists and their clinical use is extensive, therefore this review focuses on the use of dexmedetomidine and medetomidine in dogs. Emphasis is given to the cardiovascular effects and antinociceptive action of these agents.     

Medetomidine- and medetomidine-ketamine-induced immobilization in blue foxes (Alopex lagopus) and its reversal by atipamezole

The sedative and immobilizing effects of the alpha 2-adrenoceptor agonist medetomidine alone or combined with the dissociative anesthetic ketamine, were studied in blue foxes. Medetomidine at doses of 25 and 50 micrograms/kg induced moderate to deep sedation, but only with the highest medetomidine dose tested, 100 micrograms/kg, was the immobilization complete. Medetomidine 50 micrograms/kg combined with ketamine 2.5 mg/kg rapidly induced complete immobilization, characterized by good myorelaxation, and no clinically significant alterations in serially determined hematologic and serum chemistry parameters. The alpha 2-adrenoceptor antagonist atipamezole effectively reversed the medetomidine- or medetomidine-ketamine-induced immobilizations. A transient increase in heart rates was noted after each atipamezole injection.     

Chemical capture of free-ranging cattle: Immobilization with xylazine or medetomidine,and reversal with atipamezole

Twenty-nine free-ranging Norwegian cattle were captured with xylazine (n=20) or medetomidine (n=9) using a tranquilizing gun, and the time from darting to recumbency (induction time) was recorded. Twenty-eight animals were given atipamezole IV 15–100 min after darting, and the effects of the antagonist were evaluated. Blood samples (n=19) for haematology and serum chemistry were collected within 10 min after immobilization was induced.Xylazine (0.55±0.18 mg/kg; mean ± SD;n=18) or medetomidine-HCl (0.039±0.10 mg/kg;n=8) induced complete immobilization after a single darting with sternal or lateral recumbency, the induction times being 9.6±3.8 and 12.0±6.8 min, respectively. No difference in the clinical effects of the two drugs was observed.Rapid reversal was achieved with 0.057±0.017 and 0.077±0.019 mg/kg of atipamezole-HCl in xylazine- and medetomidine-treated animals, respectively. All the animals stood within 2 min after IV administration of the antagonist. Seven animals showed signs of excitement shortly after reversal, but these side-effects were of brief duration. Heavy resedation with relapse into recumbency was seen 3–4 h after reversal in two cows captured with xylazine, while moderate resedation was observed in two medetomidine-treated animals 2 h after reversal.Except for the plasma glucose concentration, which was elevated in both xylazine- and medetomidine-treated animals, the mean values of the haematological and plasma chemical parameters were within the reference ranges established for Norwegian cattle.Eight cows captured with xylazine (0.51±0.20 mg/kg) and given atipamezole-HCl (0.045±0.013 mg/kg) for reversal were in the last two months of pregnancy. All these animals calved normally and no cases of premature births or other periparturient disorders were seen.Abbreviations EDTA ethylene diamine tetraacetic acid - IM intramuscular - IV intravenous - SC subcutaneous - SD standard deviation     

A new anaesthetic circuit for use in the dog

A co–axial non–rebreathing circuit for use in small animal anaesthesia is described. The advantages and disadvantages of this type of circuit are discussed in relation to other circuits in current use.     

Evaluation of the anaesthetic effects of medetomidine and ketamine in rats and their reversal with atipamezole

ObjectivesTo compare the anaesthetic effects of varying doses of medetomidine (MED) combined with ketamine (KET) in rats, and to determine the efficacy of atipamezole (ATI) in the reversal of these effects using electroencephalogram (EEG) and assessment of clinical parameters.Study designProspective, randomized experimental trial.AnimalsTwenty-one male Sprague–Dawley rats weighing 300–398 g and aged 8–11 weeks old.MethodsThree groups received intraperitoneal injections of MED (0.2, 0.4 or 0.8 mg kg^?1) with KET (60 mg kg^?1) (MED-200, MED-400 and MED-800). Atipamezole, at doses five times higher than the previous dose of MED, was then administered intraperitoneally 70 minutes after MED-KET injection. The EEG band powers and spectral edge frequencies (SEFs), respiratory rates, reflex scores to toe-web clamping and behavioural changes were measured. Correlations between EEG parameters and reflex scores were also evaluated.ResultsThe duration of surgical anaesthesia was directly proportional to the dose of MED. Lower frequency bands (δ1 to α2) increased in all groups, and these changes were reversed by ATI. Minimal changes were observed in the higher frequency bands (β1 to γ), but their powers were increased by ATI. The SEFs were decreased in all groups, and they were reversed by ATI. While α1 band power and SEF95 showed strong correlations with the depth of anaesthesia, their changes appeared before the measured decreases in reflex score. Recovery from anaesthesia was extended by increasing the dose of MED.Conclusions and clinical relevanceSpectral EEG parameters may not accurately predict the depth of surgical anaesthesia because they had already changed during the induction of surgical anaesthesia. The ATI dose used in the present study may not be enough for complete reversal of anaesthesia induced by MED-KET.