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.     

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.     

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 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.     

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.     

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.     

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.     

Neuromuscular blocking action of vecuronium in the dog and its reversal by neostigmine

Vecuronium bromide is one of a new series of competitive or nondepolarising muscle relaxants which is closely related chemically to pancuronium. Doses of 0.06, 0.1 and 0.2 mg kg-1 produced neuromuscular block in the anaesthetised dog. There were no observable effects on arterial blood pressure. The neuromuscular block was readily reversible with neostigmine preceded by atropine.     

Chemical restraint by medetomidine and medetomidine–midazolam and its reversal by atipamezole in Japanese macaques (Macaca fuscata)

Objective To evaluate the sedative effects of medetomidine, and a medetomidine–midazolam combination, in Japanese macaques and the antagonism of medetomidine–midazolam with atipamezole. Study design Prospective randomized study. Animals Thirteen healthy Japanese macaques between 3 and 21 years old and weighing between 4.3 and 15.1 kg. Methods Medetomidine (120 µg kg^?1) alone or a medetomidine (30 µg kg^?1) plus midazolam (0.3 mg kg^?1) mixture were injected intramuscularly in the hind limb of 12 animals (n = 6 for each group) and their effects, particularly behavioural changes, response to external stimuli, sedative onset time, time to lateral recumbency and time in lateral recumbency, were monitored for 120 minutes. Another group (n = 7) were given medetomidine–midazolam and injected 30 minutes later with atipamezole (120 µg kg^?1). Behavioural changes and responses to external stimuli were assessed as before. Results Animals given medetomidine became sedated but could be aroused by external stimuli. Despite the lower (25%) dose of medetomidine involved, the effects of medetomidine–midazolam were more marked. Macaques given this combination became sedated in 4 ± 2 minutes (mean ± SD) and remained unresponsive to external stimuli for at least 60 minutes. Five out of six macaques became laterally recumbent for 74 ± 37 minutes. Intramuscular atipamezole effectively reversed sedation, shortening the arousal and total recovery time. The recovery from sedation was rapid and smooth, being completed 19 ± 11 minutes after antagonism. Conclusions The medetomidine–midazolam combination described provided useful chemical restraint and may prove useful in macaques undergoing some experimental, diagnostic or therapeutic procedures. The use of atipamezole as an antagonist increases the value of this technique in macaques.     

Sedative and cardiopulmonary effects of medetomidine and reversal with atipamezole in desert tortoises (Gopherus agassizii).

Ten desert tortoises (Gopherus agassizii) were given i.m. injections of 150 microg/kg of medetomidine. Sedation was achieved in all tortoises by 20 min postinjection and was accompanied by a significant decrease in mean heart and respiratory rates, systolic, diastolic, and mean ventricular pressures, and mean ventricular partial pressure of oxygen (PO2). There was no change in mean blood pH, HCO3, Na+, K+, ionized calcium values, and mean ventricular partial pressure of carbon dioxide (PCO2). There were statistically significant but clinically insignificant changes in mean base excess and pH-corrected ionized calcium values. Atipamezole given to five of the tortoises at 0.75 mg/kg i.m. significantly reversed the sedative effects of the medetomidine, with all tortoises returning to a normal state by 30 min after administration of the reversal agent. In comparison, the other five tortoises given an equal volume of physiologic saline in place of atipamezole (control group) remained significantly sedated for the duration of the study. In addition, the heart rate and ventricular PO2 returned to baseline, but the respiratory rate and ventricular blood pressures were not significantly altered by the atipamezole as compared with those of the control group. These cardiopulmonary and physiologic effects are similar to those seen in some domestic mammals. Medetomidine can be used to safely induce sedation in desert tortoises. For procedures lasting greater than 120 min, supplemental oxygen should be provided. Atipamezole will reverse the sedation but not all of the cardiopulmonary effects, thus necessitating continued monitoring after reversal. Future studies should address the anesthetic and cardiopulmonary effects of medetomidine in combination with other agents such as ketamine and/or butorphanol.     

搜救犬的发展概况及其使用价值

一、国外搜救犬的发展概况 国外特别是欧洲应用搜救犬的历史比较长,一百多年来,随着经济社会的发展,养犬业的发展,形成了一套适应国情的管理体制。欧洲的搜救犬由政府的紧急情况救援局或红十字协会管理,根据国土面积的大小,设一个或多个灾害搜救犬队,设施和装备由国家提供。     

Preliminary tests of a new reversible male contraceptive in bush dog, Speothos venaticus: open-ended vasectomy and microscopic reversal.

Open-ended vasectomies were performed on four male bush dogs (Speothos venaticus), with three having microscopic reversal surgery (vasovasostomy) between 10 and 20 mo post-vasectomy. The key to ease of reversal is leaving the distal (testicular) end open to allow leakage, resulting in a pressure-relieving granuloma. The proximal (abdominal) end is cauterized, providing an effective seal. This technique prevents the buildup of pressure in the epididymis, therefore limiting damage to the male's reproductive capacity. Described here are detailed procedures for both surgeries. One of the three males that underwent vasovasostomy has successfully impregnated his female partner. This study demonstrates that these techniques can be successfully applied to animals. With the two remaining pairs, none of the four individuals were proven breeders prior to the study, so it is not possible to eliminate the possibility of previously existing infertility. This technique may have limited application for carnivores, because vasectomy does not prevent potential adverse effects to females from prolonged, cyclic exposure to endogenous progesterone. In other taxonomic groups (e.g., primates, ungulates, marsupials, and rodents) in which multimale groupings are common, this reversible male sterilization technique could provide managers with the ability to control which males reproduce without eliminating their future reproductive capacity or social interaction.     

Chemical restraint-reversal with medetomidine and atipamezole in veterinary small animal practice: a survey on the opinions of the dog owners and veterinarians.

The opinions of animal owners and practising veterinarians concerning a new restraint-reversal medication (medetomidine-atipamezole) for dogs were obtained by two questionnaires in connection with a clinical study. Four alternative answers to each statement question scored as "completely agree", "somewhat agree", "somewhat disagree" and "completely disagree". The questionnaires were completed by 21 veterinarians and 245 dog owners. The overall response to the treatment was clearly positive. Both groups had a favourable attitude towards drug use with mean combined scores (from 1 to 4; 4 = most favourable) of 48.1 (max 56) for the dog owners and 39.2 (max 52) for the veterinarians. Only a little information was gained about the background of negative sentiments. Some pet owners (19%) opposed to medication on a priori grounds, some (26%) reacted strongly to the dizziness of their animals and some owners (21%) complained because of general anxiety before, during and after their pets were treated.     

Evaluation of the clinical efficacy and safety of intramuscular and intravenous doses of dexmedetomidine and medetomidine in dogs and their reversal with atipamezole

Two hundred and twelve dogs were treated either intravenously or intramuscularly with either dexmedetomidine or medetomidine in a randomised double-blinded multicentre clinical study during procedures such as dental care, radiography and otitis treatment. Sedative, analgesic and cardiorespiratory parameters and body temperature were assessed for three hours after the treatments. Approximately half the dogs were given atipamezole intramuscularly after the completion of the procedure, and the other dogs were allowed to recover spontaneously. Dexmedetomidine and medetomidine induced similar clinical effects, and the procedure was completed successfully in 97 per cent of cases. There were few adverse side effects, but they included prolonged sedation, hypothermia, apnoea and bradycardia; no adverse effects were observed after the administration of atipamezole, which effectively reversed all the clinical effects of dexmedetomidine and medetomidine.     

Pharmacological evidence for the involvement of alpha-2 adrenoceptors in the sedative effect of detomidine, a novel sedative-analgesic

The sedative effect and mechanism of action of a novel imidazole derivative, detomidine, were studied in laboratory animals. Three methods were used to quantify drug-induced sedation: (i) decrease in spontaneous activity of mice; (ii) increase in barbiturate induced anaesthesia time in mice; (iii) loss of righting reflex in chicks. Clonidine and xylazine were included in the studies for comparison. The sedative potency of detomidine was shown to be approximately equal to that of clonidine and much higher than that of xylazine. In all tests, the sedative effect of detomidine was inhibited by antagonists of alpha-2 adrenoceptors (yohimbine, rauwolscine and idazoxan) but not by alpha-1 antagonists (prazosin, corynanthine). Furthermore, an ex vivo receptor binding study in the rat showed that detomidine-induced decrease in spontaneous activity was significantly correlated to [3H]clonidine but not to [3H]prazosin displacement in brain membranes. These results show that detomidine has potent sedative effects in mice, rats and chicks, and suggest that this action is mediated through stimulation of alpha-2 adrenoceptors.