Comparison of neurologic responses to the use of medetomidine as a sole agent or preanesthetic in laboratory beagles.

Different dose regimens of medetomidine (a potent alpha 2-adrenergic agonist), adding up to a combined dose of 80 micrograms/kg, were administered to laboratory beagles to determine physiologic responses including neurologic. The study was intended to determine EEG responses where sufficient sedative and analgesic effects are reached with medetomidine and in contrast its effects when used with ketamine or halothane. Cardiopulmonary responses were very similar in each dose regimen, showing the characteristic properties of single doses of 80 micrograms/kg of medetomidine. Effective sedative and analgesic duration seemed to be a function of when the largest dose was administered. Adequate additional sedative and analgesic could be gained from injections at doses of half of the initial one. The potent sedative and analgesic effects of medetomidine confirmed by neurologic evaluation supports its potential use as a premedication to general anesthesia in dogs. In this study, 2 different doses of medetomidine were also tested as premedication to both ketamine HCI and halothane anesthesia. Neorologic responses were determined at the same time cardiopulmonary parameters, anesthetic quality, and dose requirements were recorded. Medetomidine was found to have favorable qualities in conjunction with these anesthetics. Cardiopulmonary parameters remained satisfactory in both groups as preanesthetic medication prior to halothane, but no additional benefits could be seen from doses of 40 micrograms/kg medetomidine compared to 20 micrograms/kg, except a significant 30% reduction in halothane requirement. The positive chronotropic and inotropic properties of ketamine restored the medetomidine-induced bradycardia and produced a short anesthetic period of 15 to 30 min depending on the dose of medetomidine. The quality of anesthesia was better when 40 micrograms/kg medetomidine was used, but recovery was quicker with 20 micrograms/kg medetomidine. Medetomidine significantly reduced cerebral activity as demonstrated by recordings of total amplitude and frequency evaluation of the EEG with compressed spectral analysis. This analytical method was effective in confirming clinical signs of sedation, analgesia, and anesthesia in canine subjects.     

Sedative and analgesic effects of medetomidine in dogs

The sedative and analgesic effects of medetomidine were studied in 18 laboratory beagles in a randomized cross-over study which was carried out in a double-blind fashion. Xylazine was included as a positive control and placebo as a negative control. Medetomidine was used at doses of 10, 30, 90 and 180 micrograms/kg i.m. compared to a dose of 2.2 mg/kg xylazine i.m. Parameters closely related to sedation were used to measure the degree of sedation. These were a posture variable (including evaluation of the dog's posture without external disturbance and resistance when laid recumbent) and a relaxation variable (including relaxation of the jaws, upper eyelids and anal sphincter). The first signs of sedation were recorded 1.5-3.5 min after administration of both drugs. The dogs sat down at 0.6-2.6 min post-injection and became prone at 1.9-5.9 min. Medetomidine dose-dependently affected the posture of the dogs and the relaxation variable--the higher the dose, the stronger and longer lasting the effect recorded. The sedative effect of xylazine was comparable to a medetomidine dose of 30 micrograms/kg. The analgesic effect was assessed as changes in the response to superficial pain induced by electrical stimuli. The response threshold increased significantly with both drugs and the effect of medetomidine was dose-dependent. The effects of the doses of 30 micrograms/kg medetomidine and 2.2 mg/kg xylazine did not differ significantly. In summary, medetomidine possessed an excellent sedative effect associated with analgesia in dogs.     

Sedative effects of medetomidine in pigs.

Sedative effects of medetomidine, a potent selective and specific alpha 2-adrenoceptor agonist, were evaluated in pigs using 5 different doses (30, 50, 80, 100 and 150 micrograms/kg of body weight) and compared with those of xylazine (2 mg/kg). Atropine (25 micrograms/kg) was mixed with both drugs to prevent severe bradycardia. All drugs were administered intramuscularly. Medetomidine at a dosage of 30 micrograms/kg produced more potent sedation than xylazine. The depth of sedation induced by medetomidine was dose dependent within the range from 30 to 80 micrograms/kg. At 100 or 150 micrograms/kg, the depth of sedation was mostly the similar level to that at 80 micrograms/kg but the duration was prolonged. The degree of muscle relaxation produced by medetomidine also seemed to be dose dependent from 30 to 80 micrograms/kg and was stronger than that produced by xylazine. An increase in the duration of muscle relaxation was dose dependent up to 150 micrograms/kg. No analgesic effect was produced by xylazine, however moderate analgesia was obtained by medetomidine. There were no marked changes in heart rate and respiratory rate during the observation period in pigs of any groups, however mild hypothermia after the administration of both drugs was observed. From these results, medetomidine has a significant and dose-dependent sedative effects which are much more potent than that of xylazine, and a combination of 80 micrograms/kg of medetomidine and 25 micrograms/kg of atropine is suitable for sedation with lateral recumbency and moderate muscle relaxation without notable side effects in pigs.     

Comparison of the sedative effects of medetomidine and xylazine in horses.

The sedative effects in horses of the new alpha 2 agonist medetomidine were compared with those of xylazine. Four ponies and one horse were treated on separate occasions with two doses of medetomidine (5 micrograms/kg bodyweight and 10 micrograms/kg bodyweight) and with one dose of xylazine (1 mg/kg bodyweight) given by intravenous injection. Medetomidine at 10 micrograms/kg was similar to 1 mg/kg xylazine in its sedative effect but produced more severe and more prolonged ataxia, and one animal fell over during the study. Medetomidine at 5 micrograms/kg produced less sedation but a similar degree of ataxia to 1 mg/kg xylazine.     

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.     

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 combinations of medetomidine/pethidine when used for sedation and pre-anaesthetic medication in dogs

Medetomidine, either 5, 10 or 20 (μg/kg, was administered together with pethidine, 2 mg/kg, by either the intramuscular or subcutaneous route to 88 dogs from a clinical population. Administration of all the drug combinations consistently produced profound sedation in the dogs, accompanied by dramatic reductions in heart rate. The degree of sedation was similar to that seen after 40 μg/kg medetomidine is administered on its own to dogs. Intramuscular administration produced more reliable sedation, but was associated with more pain than subcutaneous administration. In a number of dogs, sedation permitted the completion of various diagnostic or therapeutic procedures. Several dogs were anaesthetised with thiopentone and the induction doses required were characteristically low (mean doses between 2 to 3·3 mg/kg depending on the dose of medetomidine and the route of administration). Administration of atipamezole at the termination of sedation or anaesthesia, produced a rapid and full recovery (mean time to standing between seven and 11 minutes).     

Analgesic, behavioural and cardiopulmonary effects of epidurally injected medetomidine (Domitor) in goats

This study was carried out in order to evaluate the analgesic, sedative, immobilizing and cardiopulmonary effects of medetomidine in goats after lumbosacral epidural injection of three (10, 20 and 30 micrograms/kg body weight) doses. The volume of the injection for all three medetomidine doses was 5 ml in sterile water. Seventeen clinically healthy, Small East African goats of either sex and weighing between 12 and 22 kg (mean +/- SD; 14.8 +/- 2.5 kg body weight) were used. The animals were randomly assigned to two groups. Seven goats were used for evaluating analgesic, behavioural and cardiopulmonary effects while 10 were used for experimental surgery. The cardiopulmonary values and rectal temperature were determined and recorded at time 0 (preinjection) and at 5, 10, 15, 20 and 30 min, and thereafter at 15-min intervals up to 180 min after injection. Analgesia of the flank and perineum was determined at time 0 (preinjection) and at 5, 10, 15, 30, 60, 120 and 180 min using a scoring system. The spread of analgesia to the thorax, neck, forelimbs and head was also determined and recorded. The onset and duration of lateral recumbency was noted and recorded. Medetomidine at the given doses induced variable cardiopulmonary depression, which was not detrimental to the animals. All three doses (10, 20 and 30 micrograms/kg) of medetomidine induced adequate analgesia of the flank and perineum. Analgesia extended to the thorax, forelimbs, neck and head. The duration of lateral recumbency was 136 and 166 min for the 20 and 30 micrograms/kg medetomidine doses, respectively. The duration of lateral recumbency was not determined for the animal given 10 micrograms/kg medetomidine. Signs of sedation (lowering of the head, drooping of the lower lip, partial to complete closure of the eyes and salivation) were noted after administration of all three doses. It can be concluded from this study that all three doses induced adequate analgesia of the flank and perineum. Surgical analgesia of the flank of goats was achieved after lumbosacral epidural administration of 20 micrograms medetomidine/kg, diluted in 5 ml of sterile water. Surgery was not performed with the other doses (10 and 30 micrograms/kg) of medetomidine.     

A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice

Medetomidine is a relatively new sedative analgesic drug that is approved for use in dogs in Canada. It is the most potent alpha2-adrenoreceptor available for clinical use in veterinary medicine and stimulates receptors centrally to produce dose-dependent sedation and analgesia. Significant dose sparing properties occur when medetomidine is combined with other anesthetic agents correlating with the high affinity of this drug to the alpha2-adrenoreceptor. Hypoventilation occurs with medetomidine sedation in dogs; however, respiratory depression becomes most significant when given in combination with other sedative or injectable agents. The typical negative cardiovascular effects produced with other alpha2-agonists (bradycardia, bradyarrhythmias, a reduction in cardiac output, hypertension +/- hypotension) are also produced with medetomidine, warranting precautions when it is used and necessitating appropriate patient selection (young, middle-aged healthy animals). While hypotension may occur, sedative doses of medetomidine typically raise the blood pressure, due to the effect on peripheral alpha2-adrenoreceptors. Anticholinergic premedication has been recommended with alpha2-agonists to prevent bradyarrhythmias and, potentially, the reduction in cardiac output produced by these agents; however, current research does not demonstrate a clear improvement in cardiovascular function. Negatively, the anticholinergic induced increase in heart rate potentiates the alpha2-agonist mediated hypertension and may increase myocardial oxygen tension, demand, and workload. Overall, reversal with the specific antagonist atipamezole is recommended when significant cardiorespiratory complications occur. Other physiological effects of medetomidine sedation include; vomiting, increased urine volumes, changes to endocrine function and uterine activity, decreased intestinal motility, decreased intraocular pressure and potentially hypothermia, muscle twitching, and cyanosis. Decreased doses of medetomidine, compared with the recommended label dose, should be considered in combination with other sedatives to enhance sedation and analgesia and lower the duration and potential severity of the negative cardiovascular side effects. The literature was searched in Pubmed, Medline, Agricola, CAB direct, and Biological Sciences.     

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.     

Influence of medetomidine on stress-related neurohormonal and metabolic effects caused by butorphanol, fentanyl, and ketamine administration in dogs

OBJECTIVE: To examine stress-related neurohormonal and metabolic effects of butorphanol, fentanyl, and ketamine administration alone and in combination with medetomidine in dogs. ANIMALS: 10 Beagles. PROCEDURE: 5 dogs received either butorphanol (0.1 mg/kg), fentanyl (0.01 mg/kg), or ketamine (10 mg/kg) IM in a crossover design. Another 5 dogs received either medetomidine (0.02 mg/kg) and butorphanol (0.1 mg/kg), medetomidine and fentanyl (0.01 mg/kg), medetomidine and ketamine (10 mg/kg), or medetomidine and saline (0.9% NaCI) solution (0.1 mL/kg) in a similar design. Blood samples were obtained for 6 hours following the treatments. Norepinephrine, epinephrine, cortisol, glucose, insulin, and nonesterified fatty acid concentrations were determined in plasma. RESULTS: Administration of butorphanol, fentanyl, and ketamine caused neurohormonal and metabolic changes similar to stress, including increased plasma epinephrine, cortisol, and glucose concentrations. The hyperglycemic effect of butorphanol was not significant. Ketamine caused increased norepinephrine concentration. Epinephrine concentration was correlated with glucose concentration in the butorphanol and fentanyl groups but not in the ketamine groups, suggesting an important difference between the mechanisms of the hyperglycemic effects of these drugs. Medetomidine prevented most of these effects except for hyperglycemia. Plasma glucose concentrations were lower in the combined sedation groups than in the medetomidine-saline solution group. CONCLUSIONS AND CLINICAL RELEVANCE: Opioids or ketamine used alone may cause changes in stress-related biochemical variables in plasma. Medetomidine prevented or blunted these changes. Combined sedation provided better hormonal and metabolic stability than either component alone. We recommend using medetomidine-butorphanol or medetomidine-ketamine combinations for sedation or anesthesia of systemically healthy dogs.     

Sedative action of the α2-agonist medetomidine in cats

Medetomidine, a novel alpha 2-agonist drug intended for small animal sedation, was injected intramuscularly at dose rates of 0.02, 0.06 and 0.18 mg/kg. Xylazine (3.0 mg/kg) and saline were used for comparison. The five treatments were tested in a Latin square design in five cats. Treatments differed significantly in three-way analysis of variance, medetomidine inducing an increase in drowsiness with a corresponding decrease in both aroused waking and sleep determined by polygraphical criteria. The duration of effect was dose-dependent. The effect of 0.18 mg/kg medetomidine was comparable to 3.0 mg/kg of xylazine. The drugs also induced bradycardia.     

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 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.     

Antagonistic activities of atipamezole, 4-aminopyridine and yohimbine against medetomidine/ketamine-induced anaesthesia in cats

The objectives of this trial were to determine the ability of atipamezole, 4-aminopyridine and yohimbine to reverse the anaesthetic effects of a combination of medetomidine and ketamine in cats. Forty healthy cats were anaesthetised with 80 micrograms/kg medetomidine combined with 5 mg/kg ketamine. Thirty minutes later atipamezole (200 or 500 micrograms/kg), 4-aminopyridine (500 or 1000 micrograms/kg) or yohimbine (250 or 500 micrograms/kg) were injected intramuscularly. The doses of antagonists were randomised, so that each dose was administered to five cats, and 10 cats were injected only with physiological saline. Atipamezole clearly reversed the anaesthesia and bradycardia induced by medetomidine and ketamine. The mean (+/- sd) arousal times were 28 (+/- 4.7), 5.8 (+/- 1.8) and 7 (+/- 2.1) minutes in the placebo group, and the groups receiving 200 and 500 micrograms/kg atipamezole, respectively. The heart rates of the cats receiving 200 micrograms/kg atipamezole rapidly returned to values close to the initial ones, but 15 minutes after the injection of 500 micrograms/kg atipamezole a significant tachycardia was observed. All the cats showed moderate signs of ataxia during the recovery period. A dose of 500 micrograms/kg yohimbine also clearly reversed the anaesthetic effects of medetomidine/ketamine but 250 micrograms/kg was not effective. The dose of 500 micrograms/kg allowed a smooth recovery with no particular side effects except for some signs of incomplete antagonism of the ketamine effects, ie, ataxia and muscular incoordination. With 4-aminopyridine there were no statistically significant effects on the recovery, or the heart and respiratory rates of the cats anaesthetised with medetomidine/ketamine.     

Oxygenation in medetomidine-sedated dogs with and without 100% oxygen insufflation

Oxygenation status was evaluated in medetomidine-sedated dogs breathing room air (M) or 100 percent oxygen (MO2). Medetomidine (40 microg/kg IV) administration resulted in peripheral vasoconstriction and decreased venous saturation as measured by an increased oxygen extraction ratio in peripheral tissues. Providing 100 percent oxygen insufflation via face mask reduced desaturation by increasing oxygen content but did not prevent vasoconstriction or reduce the oxygen extraction ratio in peripheral tissues. Atipamezole (200 microg/kg IV) reversed medetomidine-induced vasoconstriction and increased oxygen supply to tissues as indicated by a lower tissue oxygen extraction ratio. The authors conclude that 100 percent oxygen insufflation via face mask during medetomidine sedation (40 micrograms/kg [corrected] IV) benefits tissue oxygenation in healthy dogs.     

The Analgesic Effects of Administering Fentanyl or Medetomidine in the Lumbosacral Epidural Space of Cats

The analgesic effects of fentanyl (4 μg/kg) and medetomidine (10 μg/kg) in 1 mL saline injected epidurally were measured in 15 cats. The response to an electrical cutaneous stimulus from a constant current generator was used as the index of analgesia. The stimulus was applied to a forelimb before epidural injection, and at 15, 30, 60, 90, 120, 180, 240, and 300 minutes post-injection (PI). The hindlimb was tested 5 minutes later. One mL saline only was used to control for volume of injection and saline. Medetomidine significantly increased the pain threshold for the hindlimb at 20 to 245 minutes PI compared with the preinjection level. Fentanyl significantly increased the pain threshold at 20 minutes PI only compared with preinjection levels. Medetomidine significantly increased the pain threshold of the forelimb at 15 to 120 minutes PI compared with the preinjection levels. Fentanyl did not significantly increase the pain threshold of the forelimb. Administration of medetomidine produced emesis in 12 of 15 cats in an average of 6.4 minutes PI (range, 3 to 11 minutes) and mild sedation in all cats. Injection of fentanyl produced no visible side effects in any of the cats.     

Hemodynamic Effects of Medetomidine in the Dog: A Dose Titration Study

Objective —To characterize the hemodynamic effects of medetomidine administered intravenously at doses ranging from 1 to 20 μg/kg, and to determine whether these effects are dose dependent. Study Design —Prospective randomized multidose trial. Animals —Twenty-five clinically normal male beagles (5 groups of 5), aged 1 to 4 years and weighing 13.5 ±1.7 kg. Methods —Medetomidine, at a dose of 1, 2, 5, 10, or 20 μg/kg, was administered intravenously at time 0. Heart rate, arterial pressure, central venous pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, body temperature, cardiac output, and packed cell volume were measured immediately before and at selected times after medetomidine administration (3, 7, 10, 20, 30, 40, 50, and 60 minutes in all groups, at 90 minutes for the 10 and 20 μg/kg groups, and at 120 minutes for the highest dose). Cardiac index, stroke index, rate-pressure product, systemic vascular resistance index, pulmonary vascular resistance index, and left and right ventricular stroke work indices were calculated. The degree of sedation was subjectively scored by an observer who was blinded to the treatment used. Results —Heart rate, rate-pressure product, cardiac index, and left and right ventricular stroke work indices decreased below baseline values. Central venous pressure and systemic vascular resistance index increased above baseline measurements. Except in the 2 μg/kg group, after an initial and short lasting increase, a prolonged decrease in arterial pressure was observed. Conclusions —Hemodynamic changes were observed with the intravenous (IV) administration of medetomidine, at any dose. However, the two lowest doses (1 and 2 μg/kg) produced less cardiovascular depression. Clinical Relevance —Medetomidine is an alpha-2 adrenoceptor agonist widely used in dogs, producing sedation, analgesia and cardiovascular depression. When using IV medetomidine, a reduction of the recommended dosage (ie, ±30 to 40 μg/kg) by up to 6 times did not significantly influence the cardiovascular effects.     

Clinical effects and pharmacokinetics of medetomidine and its enantiomers in dogs

The clinical effects and pharmacokinetics of medetomidine (MED) and its enanti-omers, dexmedetomidine (DEX) and levomedetomidine (LEVO) were compared in a group of six beagle dogs. The dogs received intravenously (i.v.) a bolus of MED (40 microg/kg), DEX (20 and 10 microg/kg), LEVO (20 and 10 microg/kg), and saline placebo in a blinded, randomized block study in six separate sessions. Sedation and analgesia were scored subjectively, and the dogs were monitored for heart rate, ECG lead II, direct blood pressure, respiratory rate, arterial blood gases, and rectal body temperature. Blood samples for drug analysis were taken. Peak sedative and analgesic effects were observed at mean (+/- SD) plasma levels of 18.5 +/- 4.7 ng/mL for MED40, 14.0 +/- 4.5 ng/mL for DEX20, and 5.5 +/- 1.3 ng/mL for DEX10. The overall level of sedation and cardiorespiratory effects did not differ between MED40, DEX20 and DEX10 during the first hour, apparently due to a ceiling effect. However, the analgesic effect of DEX20 lasted longer than the effect of the corresponding dose of racemic medetomidine, suggesting greater potency for dexmedetomidine in dogs. Levomedetomidine had no effect on cardio-vascular parameters and caused no apparent sedation or analgesia. The pharmacokinetics of dexmedetomidine and racemic medetomidine were similar, but clearance of levomedetomidine was more rapid (4.07 +/- 0.69 L/h/kg for LEVO20 and 3.52 +/- 1.03 for LEVO10) than of the other drugs (1.26 +/- 0.44 L/h/kg for MED40, 1.24 +/- 0.48 for DEX20, and 0.97 +/- 0.33 for DEX10).     

Comparison of three doses of dexmedetomidine with medetomidine in cats following intramuscular administration

Cats ( n  = 6) were administered dexmedetomidine (DEX) and medetomidine (MED) at three different dose levels in a randomized, blinded, cross-over study. DEX was administered at 25, 50 and 75 μg/kg (D25, D50 and D75), corresponding to MED 50, 100 and 150 μg/kg (M50, M100 and M150). Sedation, analgesia and muscular relaxation were scored subjectively. Heart and respiratory rates and rectal temperature were measured. Corresponding doses of DEX and MED were compared. Effects were also compared between dose levels for each compound. At dose level 2 (D50-M100), the duration of effective clinical sedation was significantly shorter after DEX (202.5±16.0 min) than after MED (230.0±41.2 min). Proceeding from D50-M100 to D75-M150, the duration of effective clinical sedation was increased more after DEX (by 57.5±38.4 min) than after MED (by 14.2±41.9 min) Increasing from D50-M100 to D75-M150, heart rate was further decreased after DEX (by 8.1±13.4%) but not after MED. There was no statistically significant difference between corresponding doses of DEX and MED for any of the other parameters studied. Changes in sedation, analgesia and muscular relaxation were dose-dependent. It was concluded that anaesthetic effects of medetomidine in cats are probably due entirely to its d-isomer and that dexmedetomidine at 25, 50 and 75 μg/kg induces dose-dependent sedation, analgesia and muscular relaxation of clinical significance in cats.