Some factors influencing the level of clinical sedation induced by medetomidine in rabbits

Rabbits (n=23) received intravenous bolus medetomidine at 100 mug/kg. Prior to medetomidine administration, heart and respiratory rates were measured, arterial blood was collected and analysed for plasma cortisol, glucose and albumin concentrations. Fifteen minutes after medetomidine administration, heart and respiratory rates were measured again and sedation was scored. The rabbit was afterwards anaesthetized with 20 mg/kg ketamine administered intravenously to enable spinal tap and heart puncture. Cerebrospinal fluid (CSF) was collected (this occurred 20 min post medetomidine administration) and analysed for medetomidine concentration. Blood was collected by heart puncture immediately after the spinal tap and analysed for serum medetomidine concentration. Cerebrospinal fluid medetomidine concentration correlated negatively with sedation. Serum medetomidine correlated positively with CSF medetomidine concentration. Cerebro-spinal fluid medetomidine was 17 +/- 13% of serum medetomidine concentration. Plasma cortisol and glucose concentrations correlated negatively with serum medetomidine. We conclude that after an intravenous bolus administration of a low sedative dose of medetomidine to rabbits; CSF concentration of the drug correlate negatively with sedation and that this may be because of the fact that only the free and unbound medetomidine may be available for detection in the CSF, the concentration of medetomidine detected in the CSF was much lower than that in blood and a positive correlation exists between CSF and serum medetomidine concentrations. Stress may have some effect on the distribution or metabolism of medetomidine in rabbits.     

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.     

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.     

Comparison of the clinical utility of medetomidine/ketamine and xylazine/ketamine combinations for the ovariectomy of cats

A controlled trial was conducted to assess suitability of combinations of medetomidine and ketamine for the ovariectomy of cats, to investigate the possible side effects, and to compare medetomidine/ketamine with a combination of xylazine and ketamine. Three hundred and thirty-seven cats were submitted to surgery; 100 were anaesthetised with 80 micrograms/kg medetomidine and 5 mg/kg ketamine, 137 with 80 micrograms/kg medetomidine and 7.5 mg/kg ketamine, and 100 were anaesthetised with 1 mg/kg xylazine and 10 mg/kg ketamine. The combinations were injected intramuscularly in the same syringe. The anaesthesia provided by the medetomidine/ketamine combinations was characterised by good muscle relaxation, good analgesia and minimal side effects. The only difference between the two doses of ketamine was the length of the period of anaesthesia. The advantages of the medetomidine/ketamine combination in comparison with xylazine/ketamine were the need for a lower dose of ketamine, a longer duration of action and better analgesia. Similar side effects were observed with both medetomidine/ketamine and xylazine/ketamine combinations.     

The effect of medetomidine premedication upon propofol induction and infusion anaesthesia in the dog

The effect of premedication with four different intramuscular doses of medetomidine (5.0,10.0, 20.0 and 40.0 μg.kg-¹) and a saline placebo were compared in a group of six adult beagle dogs anaesthetised with propofol on five separate occasions. Anaesthesia was induced 30 minutes after premedication and maintained by intravenous injection and continuous infusion of propofol. The effects of medetomidine were reversed with atipamezole 30 minutes after anaesthetic induction. The marked synergistic effects of medetomidine with propofol were demonstrated by a dose related reduction in the induction and infusion requirements for a similar degree of anaesthesia. The effect appeared exponential in nature; lower medetomidine doses produced a disproportionately greater effect.
The maintenance of anaesthesia with propofol following a saline placebo or low doses of medetomidine proved to be difficult. Higher doses of medetomidine required less propofol for induction and infusion and allowed a more stable anaesthesia to be maintained. Propofol produced no statistically significant change in heart rate during infusion. Changes in respiratory rate were markedly group specific. A significant reduction in respiratory rate was seen in dogs given either 5 μg.kg- or 10 μ-g.kg-¹ medetomidine. No change was recorded in dogs given 20 /μg.kg-¹ medetomidine and a significant increase was seen in dogs given 40 μg.kg-¹ medetomidine. Recovery was monitored following the termination of propofol infusion after the reversal of medetomidine using atipamezole at five times the medetomidine dose. Recovery was slower for dogs given lower doses of medetomidine and consequently higher doses of propofol.     

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.     

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.     

The effects of topical tropicamide and systemic medetomidine, followed by atipamezole reversal, on pupil size and intraocular pressure in normal dogs

Twenty normal Golden Retrievers being screeened for eye, hip and elbow diseases were given tropicamide topically and medetomidine systemically. Medetomidine effects were later reversed with systemic atipamezole. Pupil size and intraocular pressure changes were determined. Pupil size increased significantly following tropicamide administration and continued to increase slightly but significantly after medetomidine injection. It was unclear whether the slight increase in pupil size following medetomidine administration was due to continued effect of tropicamide or due to the medetomidine itself. Atipamezole did not influence pupil size. Intraocular pressure (IOP) was not affected by these drugs. Ophthalmic screening examination for inherited disease following tropicamide administration is equally feasible prior to sedation with medetomidine and after reversal with atipamezole, but not during the period of sedation.     

Sedative and cardiopulmonary effects of medetomidine hydrochloride and xylazine hydrochloride and their reversal with atipamezole hydrochloride in calves

OBJECTIVE: To assess the sedative and cardiopulmonary effects of medetomidine and xylazine and their reversal with atipamezole in calves. ANIMALS: 25 calves. PROCEDURES: A 2-phase (7-day interval) study was performed. Sedative characteristics (phase I) and cardiopulmonary effects (phase II) of medetomidine hydrochloride and xylazine hydrochloride administration followed by atipamezole hydrochloride administration were evaluated. In both phases, calves were randomly allocated to receive 1 of 4 treatments IV: medetomidine (0.03 mg/kg) followed by atipamezole (0.1 mg/kg; n = 6), xylazine (0.3 mg/kg) followed by atipamezole (0.04 mg/kg; 7), medetomidine (0.03 mg/kg) followed by saline (0.9% NaCl; 6) solution (10 mL), and xylazine (0.3 mg/kg) followed by saline solution (10 mL; 6). Atipamezole or saline solution was administered 20 minutes after the first injection. Cardiopulmonary variables were recorded at intervals for 35 minutes after medetomidine or xylazine administration. RESULTS: At the doses evaluated, xylazine and medetomidine induced a similar degree of sedation in calves; however, the duration of medetomidine-associated sedation was longer. Compared with pretreatment values, heart rate, cardiac index, and PaO(2) decreased, whereas central venous pressure, PaCO(2), and pulmonary artery pressures increased with medetomidine or xylazine. Systemic arterial blood pressures and vascular resistance increased with medetomidine and decreased with xylazine. Atipamezole reversed the sedative and most of the cardiopulmonary effects of both drugs. CONCLUSIONS AND CLINICAL RELEVANCE: At these doses, xylazine and medetomidine induced similar degrees of sedation and cardiopulmonary depression in calves, although medetomidine administration resulted in increases in systemic arterial blood pressures. Atipamezole effectively reversed medetomidine- and xylazine-associated sedative and cardiopulmonary effects in calves.     

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.     

Effects of intramuscular administration of low doses of medetomidine and medetomidine-butorphanol in middle-aged and old dogs.

OBJECTIVE: To determine effects of low doses of medetomidine administered with and without butorphanol and glycopyrrolate to middle-aged and old dogs. DESIGN: Prospective randomized clinical trial. ANIMALS: 88 healthy dogs > or = 5 years old. PROCEDURE: Dogs were assigned randomly to receive medetomidine (2, 5, or 10 micrograms/kg [0.9, 2.3, or 4.6 micrograms/lb] of body weight, i.m.) alone or with glycopyrrolate (0.01 mg/kg [0.005 mg/lb], s.c.), medetomidine (10 micrograms/kg) and butorphanol (0.2 mg/kg [0.1 mg/lb], i.m.), or medetomidine (10 micrograms/kg), butorphanol (0.2 mg/kg), and glycopyrrolate (0.01 mg/kg). Anesthesia was induced with thiopental sodium and maintained with isoflurane. Degree of sedation and analgesia were determined before and after medetomidine administration. Respiratory rate, heart rate, and mean arterial blood pressure were determined 10 and 30 minutes after medetomidine administration. Adverse effects and amounts of thiopental and isoflurane used were recorded. RESULTS: Sedation increased after medetomidine administration in 79 of 88 dogs, but decreased in 7 dogs that received 2 or 5 micrograms of medetomidine/kg. Mean postsedation analgesia score and amounts of thiopental and isoflurane used were less in dogs that received medetomidine and butorphanol, compared with other groups. Respiratory rate, heart rate, and blood pressure were not different among groups. Significantly more adverse effects developed in dogs that did not receive glycopyrrolate. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of medetomidine (10 micrograms/kg, i.m.) and butorphanol (0.2 mg/kg, i.m.) induced sedation and analgesia and reduced amounts of thiopental and isoflurane required for anesthesia in middle-aged and old dogs. Glycopyrrolate decreased frequency of medetomidine-associated adverse effects.     

Effects of medetomidine,l‐methadone,and their combination on arterial blood gases in dogs

ObjectiveTo investigate the influence of l–methadone on medetomidine–induced changes in arterial blood gases and clinical sedation in dogs.Study designProspective experimental cross–over study (Latin square design).AnimalsFive 1–year–old purpose bred laboratory beagle dogs of both sexes.MethodsEach dog was treated three times: medetomidine (20 μg kg^?1 IV), l–methadone (0.1 mg kg^?1 IV) and their combination. Arterial blood was collected for blood gas analysis. Heart and respiratory rates were recorded, and clinical sedation and reaction to a painful stimulus were scored before drug administration and at various time points for 30 minutes thereafter.ResultsArterial partial pressure of oxygen decreased slightly after medetomidine administration and further after medetomidine/l–methadone administration (range 55.2–86.7 mmHg, 7.4–11.6 kPa, at 5 minutes). A slight increase was detected in arterial partial pressure of carbon dioxide after administration of l–methadone and medetomidine/l–methadone (42.6 ± 2.9 and 44.7 ± 2.4 mmHg, 5.7 ± 0.4 and 6.0 ± 0.3 kPa, 30 minutes after drug administration, respectively). Arterial pH decreased slightly after administration of l–methadone and medetomidine/l–methadone. Heart and respiratory rates decreased after administration of medetomidine and medetomidine/l–methadone, and no differences were detected between the two treatments. Most dogs panted after administration of l–methadone and there was slight sedation. Medetomidine induced moderate or deep sedation, and all dogs were deeply sedated after administration of medetomidine/l–methadone. Reaction to a noxious stimulus was strong or moderate after administration of methadone, moderate or absent after administration of medetomidine, and absent after administration of medetomidine/l–methadone.Conclusions and clinical relevanceAt the doses used in this study, l–methadone potentiated the sedative and analgesic effects and the decrease in arterial oxygenation induced by medetomidine in dogs, which limits the clinical use of this combination.     

Seizures during medetomindine sedation and local anaesthesia in two dogs undergoing skin biopsy

Each of two dogs presented for multiple skin biopsies were sedated with intravenous medetomidine and lignocaine was injected subcutaneously to provide local anaesthesia for skin biopsy. One dog had a seizure during skin biopsy and again immediately following reversal of medetomidine with atipamezole. The other dog developed seizures 2 h following skin biopsy at which time the medetomidine was reversed with atipamezole. Both dogs were neurologically normal with no history of seizures prior to the procedure and remained neurologically normal for 14 weeks and 9 months, respectively, following the procedure. A drug interaction between the α₂-adrenergic agonist medetomidine and lignocaine is suspected and highlights the potential for seizures following the subcutaneous administration of relatively large doses of lignocaine under medetomidine sedation.     

Effects of a peripheral alpha2 adrenergic-receptor antagonist on the hemodynamic changes induced by medetomidine administration in conscious dogs

OBJECTIVE: To evaluate the effects of administration of a peripheral alpha(2)-adrenergic receptor antagonist (L-659,066), with and without concurrent administration of glycopyrrolate, on cardiopulmonary effects of medetomidine administration in dogs. ANIMALS: 6 healthy adult dogs. PROCEDURES: Dogs received saline (0.9% NaCl) solution (saline group), L-659,066 (group L), or L-659,066 with glycopyrrolate (group LG). These pretreatments were followed 10 minutes later by administration of medetomidine in a randomized crossover study. Hemodynamic measurements and arterial and mixed-venous blood samples for blood gas analysis were obtained prior to pretreatment, 5 minutes after pretreatment, and after medetomidine administration at intervals up to 60 minutes. RESULTS: After pretreatment in the L and LG groups, heart rate, cardiac index, and partial pressure of oxygen in mixed-venous blood (PvO2) values were higher than those in the saline group. After medetomidine administration, heart rate, cardiac index, and PvO2 were higher and systemic vascular resistance, mean arterial blood pressure, and central venous pressure were lower in the L and LG groups than in the saline group. When the L and LG groups were compared, heart rate was greater at 5 minutes after medetomidine administration, mean arterial blood pressure was greater at 5 and 15 minutes after medetomidine administration, and central venous pressure was lower during the 60-minute period after medetomidine administration in the LG group. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of L-659,066 prior to administration of medetomidine reduced medetomidine-induced cardiovascular changes in healthy dogs. No advantage was detected with concurrent administration of L-659,066 and glycopyrrolate.     

Effects of preemptive atropine administration on incidence of medetomidine-induced bradycardia in dogs

OBJECTIVE: To determine the cardiorespiratory effects of preemptive atropine administration in dogs sedated with medetomidine. DESIGN: Randomized crossover trial. ANIMALS: 12 healthy adult dogs. PROCEDURES: Dogs underwent 6 treatments. Each treatment consisted of administration of atropine (0.04 mg/kg [0.018 mg/lb] of body weight, IM) or saline solution (0.9% NaCl, 1 ml, IM) and administration of medetomidine (10, 20, or 40 microg/kg [4.5, 9.1, or 18.2 microg/lb], IM) 10 minutes later. Treatments were administered in random order, with a minimum of 1 week between treatments. Cardiorespiratory effects before and after atropine and medetomidine administration were assessed. Duration of lateral recumbency and quality of sedation and recovery were assessed. RESULTS: Bradycardia (heart rate < 60 beats/min) was seen in all dogs when saline solution was administered followed by medetomidine, and the dose of medetomidine was not associated with severity or frequency of bradycardia or second-degree heart block. However, a medetomidine dose-dependent increase in mean and diastolic blood pressures was observed, regardless of whether dogs received saline solution or atropine. Preemptive atropine administration effectively prevented bradycardia and second-degree heart block but induced pulsus alternans and hypertension. The protective effects of atropine against bradycardia lasted 50 minutes. Blood gas values were within reference limits during all treatments and were not significantly different from baseline values. Higher doses of medetomidine resulted in a longer duration of lateral recumbency. CONCLUSIONS AND CLINICAL RELEVANCE: Preemptive administration of atropine in dogs sedated with medetomidine effectively prevents bradycardia for 50 minutes but induces hypertension and pulsus alternans.     

An evaluation of the influence of medetomidine hydrochloride and atipamezole hydrochloride on the arrhythmogenic dose of epinephrine in dogs during halothane anesthesia.

Alterations in the arrhythmogenic dose of epinephrine (ADE) were determined following administration of medetomidine hydrochloride (750 micrograms/M2) and a saline placebo, or medetomidine hydrochloride (750 micrograms/M2), followed by specific medetomidine reversal agent, atipamezole hydrochloride (50 micrograms/kg) 20 min later, in halothane-anesthetized dogs (n = 6). ADE determinations were made prior to the administration of either treatment, 20 min and 4 h following medetomidine/saline or medetomidine/atipamezole administration. Epinephrine was infused for 3 min at increasing dose rates (2.5 and 5.0 micrograms/kg/min) until the arrhythmia criterion (4 or more intermittent or continuous premature ventricular contractions) was reached. The interinfusion interval was 20 min. There were no significant differences in the amount of epinephrine required to reach the arrhythmia criterion following the administration of either treatment. In addition, the ADE at each determination was not different between treatment groups. In this study, the administration of medetomidine to halothane-anesthetized dogs did not alter their arrhythmogenic response to infused epinephrine.     

Actions and pharmacokinetic properties of the α2-adrenergic agents, medetomidine and atipamezole, in rainbow trout (Oncorhynchus mykiss)

The effects of medetomidine and atipamezole were examined in rainbow trout. Medetomidine proved to be an effective sedative but not an anaesthetic; its effects were antagonised by atipamezole. The clinical signs of medetomidine sedation were rapid settling to the bottom of the tank followed by progressive ataxia. The sedative effect was dose-dependent: at 1 mg/l, one of 6 fish rested on its side after 10 min, whereas at 20 mg/l all 6 rested on their sides. No loss of consciousness occurred. Atipamezole at 6 times the medetomidine concentration antagonised sedation. The average time before fish exposed to medetomidine alone showed avoidance reactions was 10 h, more than 5 times longer than the mean time in fish exposed to medetomidine and then atipamezole. During exposure to medetomidine (5 mg/l) opercular movement rate decreased from 80/min to 20/min. The nature of opercular excursions also changed from being rapid and shallow to slow and deep. Respiratory movements increased after transfer to the bath containing atipamezole. Medetomidine had a marked effect upon skin colour, with fish becoming very pale a few min after exposure. Normal pigmentation was not restored until 4.5 days after exposure to medetomidine alone, but returned to normal after 10 min exposure to atipamezole solution. The half-life (t¹/₂ lambda_z) for medetomidine was 5.5 h. For atipamezole, it was 8.6 h.     

Medetomidine, a new sedative-analgesic for use in the dog and its reversal with atipamezole

The sedative and physiological effects of intramuscular medetomidine (20 and 40 μg/kg) in dogs were compared with those of xylazine (2 mg/kg). The efficacy of atipamezole (200 μg/kg), as an antagonist given 15 or 45 minutes after medetomidine (40 μg/kg) was studied. Following medetomidine, onset of sedation was rapid, and depth and duration of sedation were dose dependent. The higher dose produced jaw relaxation, depression of the pedal reflex, downward rotation of the eye and dogs could be positioned for radiography of the hips. Side effects were similar after either medetomidine or xylazine, and included bradycardia, a fall in respiratory rate and muscle tremor. Vomiting during induction was less frequent after medetomidine than after xylazine. Intramuscular administration of atipamezole rapidly reversed the sedative effects of medetomidine. Signs of arousal were seen within three minutes; all dogs could stand within 10 minutes and appeared clinically normal. Heart and respiratory rates rose, but did not return to presedation values. Relapse to sedation was not noted.     

Cardiovascular effects of medetomidine, detomidine and xylazine in horses

The cardiovascular effects of medetomidine, detomidine, and xylazine in horses were studied. Fifteen horses, whose right carotid arteries had previously been surgically raised to a subcutaneous position during general anesthesia were used. Five horses each were given the following 8 treatments: an intravenous injection of 4 doses of medetomidine (3, 5, 7.5, and 10 microg/kg), 3 doses of detomidine (10, 20, and 40 microg/kg), and one dose of xylazine (1 mg/kg). Heart rate decreased, but not statistically significant. Atrio-ventricular block was observed following all treatments and prolonged with detomidine. Cardiac index (CI) and stroke volume (SV) were decreased with all treatments. The CI decreased to about 50% of baseline values for 5 min after 7.5 and 10 microg/kg medetomidine and 1 mg/kg xylazine, for 20 min after 20 microg/kg detomidine, and for 50 min after 40 microg/kg detomidine. All treatments produced an initial hypertension within 2 min of drug administration followed by a significant decrease in arterial blood pressure (ABP) in horses administered 3 to 7.5 microg/kg medetomidine and 1 mg/kg xylazine. Hypertension was significantly prolonged in 20 and 40 microg/kg detomidine. The hypotensive phase was not observed in 10 microg/kg medetomidine or detomidine. The changes in ABP were associated with an increase in peripheral vascular resistance. Respiratory rate was decreased for 40 to 120 min in 5, 7.5, and 10 microg/kg medetomidine and detomidine. The partial pressure of arterial oxygen decreased significantly in 10 microg/kg medetomidine and detomidine, while the partial pressure of arterial carbon dioxide did not change significantly. Medetomidine induced dose-dependent cardiovascular depression similar to detomidine. The cardiovascular effects of medetomidine and xylazine were not as prolonged as that of detomidine. KEY WORDS: cardiovascular effect, detomidine, equine, medetomidine, xylazine.     

The effects of medetomidine on cardiac function in normal cats measured by radionuclide ventriculography

To assess the effects of medetomidine, an α₂-adrenoceptor agonist, on cardiac function, radionuclide ventriculograms (RNV) were performed in 7 normal anesthetised cats before and after im administration of the drug. Ejection fraction (EF), peak ventricular ejection rate (PVER), peak ventricular filling rate (PVFR), time to peak ejection (TPE) and time to peak filling (TPF) were determined. Medetomidine caused significant reductions in EF (baseline 55.0 ± 10.8%, post medetomidine 43.3 ± 10.7%), PVER (baseline 4.38 ± 0.83 EDV/s, post medetomidine 3.28 ± 0.73 EDV/s) and PVFR (baseline 4.46 ± 1.42 EDV/s, post medetomidine 3.05 ± 1.27 EDV/s). There was also a significant decrease in heart rate following medetomidine administration (baseline 115 ± 27.2 bpm, post medetomidine 100 ± 21.2 bpm). The TPE and TPF did not change significantly following medetomidine. The observed decrease in cardiac function may have been caused by a drug-induced increase in systemic vascular resistance, and the bradycardia due to central nervous system depression.