The correlation of the thermal and mechanical antinociceptive activity of pethidine hydrochloride with plasma concentrations of the drug in sheep

The analgesic activity of pethidine was measured in eight sheep using both thermal and mechanical test systems. Pethidine, at a dose rate of 5 mg/kg body weight given intravenously, produced a significant degree of antinociception to thermal pain for 30 min (on average) but gave only a few minutes of significant analgesia when tested in the mechanical pressure system. Analgesia in both systems was abolished by pretreatment with naloxone. Pharmacokinetic analyses of plasma levels of pethidine after intravenous (i.v.) injection were carried out. Plasma concentrations of the drug exhibited a rapid biexponential pattern of decline with an average distribution half-life of 0.99 min and an elimination half-life of 12.8 min. Correlation of plasma levels of the drug with the presence of a significant degree of antinociception in the thermal test system enabled 'critical' analgesic levels of pethidine to be defined for sheep (0.93 microgram/ml).     

The antinociceptive activity and respiratory effects of fentanyl in sheep

The analgesic activity of fentanyl was measured in sheep using both thermal and mechanical test systems. Fentanyl at a dose rate of 5 μg/kg given intravenously (iv) produced significant analgesia to thermal pain for some 30 mins but no detectable mechanical antinociceptive activity. However, at a dose rate of 10 μg/kg the drug produced both thermal (for 60 mins) and mechanical (40 mins) antinociceptive effects. In one sheep a dose of 20 μg/kg produced thermal analgesia for 110 mins and mechanical antinociception for 60 mins. Following iv injection at 10 μg/kg in five of the sheep, there was a brief period of respiratory depression evidenced by a significant fall in PaCO₂ of the order of 25 per cent and an increase in PCO₂ levels, but these changes were short lived and levels were back to normal at 15 mins after injection.     

Effects of acepromazine, butorphanol and buprenorphine on thermal and mechanical nociceptive thresholds in horses

Reasons for performing study: To investigate the antinociceptive effects of buprenorphine administered in combination with acepromazine in horses and to establish an effective dose for use in a clinical environment. Objectives: To evaluate the responses to thermal and mechanical stimulation following administration of 3 doses of buprenorphine compared to positive (butorphanol) and negative (glucose) controls. Methods: Observer blinded, randomised, crossover design using 6 Thoroughbred geldings (3–10 years, 500–560 kg). Thermal and mechanical nociceptive thresholds were measured 3 times at 15 min intervals. Horses then received acepromazine 0.05 mg/kg bwt with one of 5 treatments i.v.: 5% glucose (Glu), butorphanol 100 µg/kg bwt (But) buprenorphine 5 µg/kg bwt (Bup5), buprenorphine 7.5 µg/kg bwt (Bup7.5) and buprenorphine 10 µg/kg bwt (Bup10). Thresholds were measured 15, 30, 45, 60, 90, 120, 150, 180, 230 min, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 24 h post treatment administration. The 95% confidence intervals for threshold temperature (ΔT) for each horse were calculated and an antinociceptive effect defined as ΔT, which was higher than the upper limit of the confidence interval. Duration of thermal antinociception was analysed using a within‐subjects ANOVA and peak mechanical thresholds with a general linear model with post hoc Tukey tests. Significance was set at P<0.05. Results: Mean (± s.d.) durations of thermal antinociception following treatment administration were: Glu 0.5 (1.1), But 2.9 (2.0), Bup5 7.4 (2.3), Bup7.5 7.8 (2.7) and Bup10 9.4 (1.1) h. B5, B7.5 and B10 were significantly different from Glu and But. No serious adverse effects occurred, although determination of mechanical thresholds was confounded by locomotor stimulation. Conclusions: Administration of acepromazine and all doses of buprenorphine produced antinociception to a thermal stimulus for significantly longer than acepromazine and either butorphanol or glucose. Potential relevance: This study suggests that buprenorphine has considerable potential as an analgesic in horses and should be examined further under clinical conditions and by investigation of the pharmacokinetic/pharmacodynamic profile.     

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.     

Thermal antinociception after dexmedetomidine administration in cats: a dose-finding study

The optimum dose of dexmedetomidine for antinociception to a thermal stimulus was determined in a crossover study of 12 cats. In five treatment groups ( n  = 10 per group), dexmedetomidine was administered intramuscularly (i.m.) at 2, 5, 10, 20 and 40 μg/kg; positive and negative controls were administered buprenorphine (20 μg/kg, i.m.) and 0.9% saline (0.006 mL/kg, i.m.) respectively. Baseline thermal thresholds and visual analogue scale (VAS) sedation scores were obtained prior to drug treatment and then at regular intervals until 24 h after administration. The summary measures of overall mean thresholds and overall mean VAS scores were investigated using a univariate general linear model for multiple factors with post hoc Tukey's tests ( P  < 0.05). Only dexmedetomidine at 40 μg/kg displayed an analgesic effect (less than that of buprenorphine). The VAS for sedation did not significantly affect the thresholds obtained and treatment was the only significant factor to influence VAS. Dexmedetomidine resulted in higher VAS for sedation than saline and buprenorphine. Dexmedetomidine at 40 μg/kg significantly increased nociceptive thresholds compared with saline control, but less than buprenorphine. Dexmedetomidine produced dose-dependent sedation, but only the highest dose produced analgesia, suggesting that induction of analgesia requires the highest dose (or an additional analgesic) in the clinical setting.     

The toxicity of phomopsin for sheep

Pure phomopsin was administered to young Merino x Border Leicester wethers by single subcutaneous (SC) and by single and multiple intraruminal (IR) injection. The toxicity after IR injection was influenced by the size of individual doses and the time over which the total dose was given. At high levels of ingestion the toxicity of phomopsin may be limited by absorption rates; with low daily doses the capacity to repair liver damage may be sufficient to prevent cumulative effects. By SC injection a single dose of 10 micrograms/kg approximated the LD50. By IR injection the overall clinical, biochemical and histological responses closest to these of this SC dose resulted from a single dose of 1,000 micrograms/kg. The same total dose administered at daily rates of 50 or 200 micrograms/kg was more toxic and killed all sheep. A single dose of 500 micrograms/kg caused significant liver damage, but no deaths. Single doses of 125 and 250 micrograms/kg and repeated daily doses of 12.5 micrograms/kg over 16 weeks caused no detectable tissue damage. Inappetence was the most sensitive indicator of phomopsin toxicity. About 10% of the sheep differed substantially from the rest of the flock in their susceptibility to phomopsin poisoning.     

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.     

Pharmacokinetics and physiological effects of two intravenous infusion rates of morphine in conscious dogs

This study examined the pharmacokinetics and physiologic effects of two infusions rates of morphine in conscious dogs. Five adult dogs were randomly studied at weekly intervals. An initial dose of either 0.3 or 0.6 mg/kg were each followed by infusions of 0.17 and 0.34 mg/kg/h. Plasma morphine concentrations, physiological parameters, sedation and mechanical antinociception were evaluated during each infusion. Morphine was assayed by high pressure liquid chromatography (HPLC) with electrochemical coulometric detection and pharmacokinetic parameters were calculated. Data were fitted to a bi-compartment model with a rapid distribution (<1 min for both doses) and slower termination rate. For the high and low doses, respectively, mean+/-SD terminal half-life was 38+/-5 and 27+/-14 min, apparent volumes of distribution at steady-state were 1.9+/-0.5 and 1.3+/-0.8 L/kg, with clearances of 50+/-15 and 67+/-20 mL/kg/min. Steady-state plasma concentrations ranged from 93 to 180 ng/mL and 45 to 80 ng/mL in the high and low doses, respectively. Respiratory rate increased significantly, pulse oximetry remained>95% and body temperature decreased significantly during both infusions. No vomition or neuroexcitation occurred. Sedation and mechanical antinociception were both mild during the lower infusion rate, and mild to moderate during the higher infusion rate. In conclusion, morphine pharmacokinetics was not altered by increasing infusion rates, producing stable, long-lasting plasma concentrations.     

Antinociceptive Effects of Oxymorphone-Butorphanol-Acepromazine Combination in Cats

Objective—To determine the antinociceptive effects of oxymorphone, butorphanol, and acepromazine individually and in combination to a noxious visceral stimulus in cats. Study Design—Randomized, blinded controlled study. Animals—Eight healthy mixed-breed cats (four male, four female) weighing 4.4 ± 1.2 kg and aged 1 to 2 years old. Methods—A silastic balloon catheter was inserted per rectum and inflated at various pressures. Physiological parameters (respiratory rate, pulse rate, and blood pressure) were also recorded. Subjects were administered individual and combined intravenous (IV) doses of 0.025, 0.05, 0.10, and 0.20 mg/kg oxymorphone and 0.025, 0.05, 0.10, and 0.20 mg/kg butorphanol. A further study of various ratios of butorphanol and oxymorphone (3:1, 2:1, 1:1, 1:2, and 1:3), at a combined equivalent dose of 0.1 mg/kg, was performed in four cats per dose combination. In a separate study, four cats were administered combined IV doses of 0.05 mg/kg each of oxymorphone and butorphanol or 0.05 mg/kg each of oxymorphone, butorphanol, and acepromazine. Results—Combined doses of 0.05 and 0.10 mg/kg of oxymorphone and butorphanol showed mainly additive with some synergistic antinociceptive interactions and the combined dose of 0.2 mg/kg of each agent demonstrated additional antinociceptive effects, P < .05. Additional studies showed that various ratios of the two agents at a total combined dose of 0.10 mg/kg IV did not produce levels of antinociception that were significantly different from each other, P > .05. Acepromazine (ACE) significantly increased the magnitude of antinociception at 15 minutes when administered in combination with oxymorphone and butorphanol, P < .05. Also, physiological variables were unaffected by these drug combinations. Conclusions—Low doses of oxymorphone and butorphanol in combination can produce greater levels of antinociception than when used individually. ACE, in conjunction with oxymorphone and butorphanol, produced even greater levels of antinociception than the two-opioid drug combination. Clinical Relevance—Oxymorphone, butorphanol, and ACE can be used in combination to produce additive or synergistic effects without adverse effects in cats. These data suggest that ACE and butorphanol at low doses given as preanesthetic medication followed by a mu opioid (eg, oxymorphone) after surgery at low doses may provide an effective method of pain management in the cat.     

Sedative effect of detomidine in infant calves.

Detomidine administered intramuscularly at a dose of 10, 20 or 40 micrograms/kg body mass was evaluated for its sedative effects in 15 unfasted infant calves (age: 15-20 days; body mass: 18-33 kg). The drug produced dose-dependent sedation. At a dose of 10 micrograms/kg detomidine produced effective sedation for 30 to 45 min without any observable analgesia. At doses of 20 or 40 micrograms/kg it caused deep sedation, sternal recumbency, and moderate analgesia of the trunk. Hyperglycaemia was recorded at all dose levels. The changes in respiratory rate, rectal temperature, haemoglobin, packed cell volume, total erythrocyte count and plasma concentration of total protein were not significant.     

Analgesic activity and respiratory effects of butorphanol in sheep

The analgesic drug butorphanol tartrate has proved useful clinically in horses and dogs but its analgesic profile had not yet been investigated in sheep. This study was initiated to determine the thermal and mechanical antinociceptive activity of butorphanol (at the dose rates 0.05, 0.1 and 0.2 mg kg-1) in sheep. The drug produced significant analgesia in the thermal test system, the duration of which was dose related but no significant elevation in mechanical pressure thresholds could be detected. In a further set of experiments the dose rate was increased to 0.4 mg kg-1 and mechanical testing was repeated. There was still no clinically significant elevation in pressure thresholds. At a dose rate of 0.2 mg kg-1 the drug had no detectable effect on respiratory blood gas tensions. Behavioural changes were severe if a dose rate of 0.2 mg kg-1 was exceeded.     

Antinociceptive effects after oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis)

Objective-To evaluate antinociceptive effects on thermal thresholds after oral administration of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). Animals-15 healthy adult Hispaniolan Amazon parrots. Procedures-2 crossover experiments were conducted. In the first experiment, 15 parrots received 3 treatments (tramadol at 2 doses [10 and 20 mg/kg] and a control suspension) administered orally. In the second experiment, 11 parrots received 2 treatments (tramadol hydrochloride [30 mg/kg] and a control suspension) administered orally. Baseline thermal foot withdrawal threshold was measured 1 hour before drug or control suspension administration; thermal foot withdrawal threshold was measured after administration at 0.5, 1.5, 3, and 6 hours (both experiments) and also at 9 hours (second experiment only). Results-For the first experiment, there were no overall effects of treatment, hour, period, or any interactions. For the second experiment, there was an overall effect of treatment, with a significant difference between tramadol hydrochloride and control suspension (mean change from baseline, 2.00° and -0.09°C, respectively). There also was a significant change from baseline for tramadol hydrochloride at 0.5, 1.5, and 6 hours after administration but not at 3 or 9 hours after administration. Conclusions and Clinical Relevance-Tramadol at a dose of 30 mg/kg, PO, induced thermal antinociception in Hispaniolan Amazon parrots. This dose was necessary for induction of significant and sustained analgesic effects, with duration of action up to 6 hours. Further studies with other types of noxious stimulation, dosages, and intervals are needed to fully evaluate the analgesic effects of tramadol hydrochloride in psittacines.     

Effects of intravenously administered glycopyrrolate in anesthetized horses.

The purpose of this study was to determine the heart rate (HR) and blood pressure (BP) effect of glycopyrrolate in anesthetized horses with low HR (< or = 30 beats/min). The horses were randomly treated with glycopyrrolate (2.5 micrograms/kg body weight (BW)) or saline, intravenously (i.v.) (n = 17). If HR failed to increase (by > 5 beats/min within 10 min), glycopyrrolate (same dose) was administered. Heart rate increased by > 5 beats/min in 3 out of 9 horses following the initial glycopyrrolate treatment. Overall changes in HR and mean BP were not significantly different, while systolic and diastolic BP increased significantly (P < 0.025 using a Bonferroni corrected paired t-test). On the 2nd treatment, 3 out of 7 horses given 2.5 micrograms/kg BW glycopyrrolate, and 4 out of 5 horses given 5.0 micrograms/kg BW (total dose) showed an increase in heart rate of > 5 beats/min, which was significant. A significant increase in BP was produced following treatment with 2.5 micrograms/kg BW, but not following 5.0 micrograms/kg BW. A final increase in HR, of > 5 beats/min, was associated with a significant rise in BP (P < 0.05 using an unpaired t-test). In conclusion, an increase in HR can occur with 2.5 to 5.0 micrograms of glycopyrrolate/kg BW, i.v., and results in improvement in BP in anesthetized horses.     

An assessment of the peripheral antinociceptive potential of remoxipride, clonidine and fentanyl in sheep using the forelimb tourniquet

A modification of the intravenous regional anaesthesia technique was used to assess the peripheral antinociceptive effect of remoxipride, clonidine and fentanyl. Drugs administered intravenously via peripheral catheters were restricted to the distal limb and nociceptive threshold test site by prior inflation of a tourniquet proximal to both the catheter and a threshold-testing device. Lignocaine (1 mg/kg) induced peripheral antinociception during tourniquet inflation. Clonidine (6 μg/kg) only induced significant elevations in thresholds after tourniquet deflation. A low dose of remoxipride (2 mg/kg), which had no systemic antinociceptive effect, produced antinociception after its restriction to the periphery. Peripheral administration of saline and tourniquet-induced restriction of blood flow to the distal limb did not alter threshold values. Peripheral administration of fentanyl was used to test a further modification of the injection protocol designed to reduce the incidence of leakage into the systemic circulation. Fentanyl administration (11.2 μg/kg) failed to elicit an increase in thresholds when it was restricted to the distal limb test site. The contribution of a peripheral mechanism to the antinociception induced by systemic administration of a higher remoxipride dose (7.5 mg/kg) was investigated using an inflated tourniquet to exclude remoxipride from the periphery. Exclusion of remoxipride from the periphery reduced its antinociceptive effect, i.e. threshold values were lower than if remoxipride was allowed free access to the limb prior to tourniquet inflation.
The technique described here was effective in demonstrating that the increase in noninflammatory nociceptive thresholds seen with clonidine and fentanyl is not peripherally mediated whilst that seen with remoxipride has a peripheral component.     

Characterization of the antinociceptive and sedative effect of amitraz in horses

Amitraz, an acaricide used to control ectoparasites in animals has a complex pharmacological activity, including α₂-adrenergic agonist action. The purpose of this research was to investigate the possible antinociceptive and/or sedative effect of amitraz in horses. The sedative effect of the intravenous (i.v.) injection of dimethylformamide (DMF, 5 mL, control) or amitraz (0.05, 0.10, 0.15 mg/kg), was investigated on the head ptosis test. The participation of α₂-adrenergic receptors in the sedative effect provoked by amitraz was studied by dosing yohimbine (0.12 mg/kg, i.v.). To measure the antinociception, xylazine hydrochloride (1 mg/kg, i.v., positive control) and the same doses of amitraz and DMF were used. A focused radiant light/heat directed onto the fetlock and withers of a horse were used as a noxious stimulus to measure the hoof withdrawal reflex latency (HWRL) and the skin twitch reflex latency (STRL). The three doses of amitraz used (0.05, 0.10 and 0.15 mg/kg) provoked a dose-dependent relaxation of the cervical muscles. The experiments with amitraz and xylazine on the HWRL showed that after i.v. administration of all doses of amitraz there was a significant increase of HWRL up to 150 min after the injections. Additionally, there was a significant difference between control (DMF) and positive control (xylazine) values up to 30 min after drug injection. On the other hand, the experiments on the STRL show that after administration of amitraz at the dose of 0.15 mg/kg, a significant increase in STRL was observed when compared with the control group. This effect lasted up to 120 min after injection. However, no significant antinociceptive effect was observed with the 0.05 and 0.10 mg/kg doses of amitraz or at the 1.0 mg/kg dose of xylazine.     

Cardiopulmonary effects of dopamine hydrochloride in anaesthetised horses

Dopamine hydrochloride was infused intravenously into six horses anaesthetised with halothane. Three dose rates; 0.5, 2.5 and 5.0 micrograms/kg/min, were evaluated in each horse. The cardiac output was significantly increased at 15 and 30 mins following administration of dopamine at 2.5 and 5.0 micrograms/kg/min. The heart rate, facial artery pressure and pulmonary artery pressure remained unchanged. Total peripheral resistance was significantly decreased at 30 mins with 2.5 micrograms/kg/min and at 15 and 30 mins with 5.0 micrograms/kg/min. No significant change was produced in packed cell volume, total protein, white blood cell count, platelets, glucose or lactate at any infusion rate. Supraventricular premature contractions occurred in one horse and episodes of tachycardia occurred in two horses during infusion of dopamine at 5.0 micrograms/kg/min. The results of the investigation demonstrated that dopamine administered at 2.5 and 5.0 micrograms/kg/min effectively increased the cardiac output of halothane anaesthetised horses and that dopamine at the high dosage may cause dysrhythmias.     

Evaluation of detomidine as a sedative in goats.

Intramuscular (i.m.) and intravenous (i.v.) administration of detomidine at doses of 10, 20 and 40 micrograms/kg body mass was evaluated for its sedative and analgesic properties in 15 goats (Capra hircus). The drug produced dose- and route-dependent sedation. The 10 micrograms/kg dose was effective only when administered i.v. There was no observable analgesia at this dose. Higher doses produced effective sedation and moderate analgesia of the body with either route of administration. Severe ataxia and sternal recumbency were seen in all the animals after the dose of 40 micrograms/kg. Other effects of detomidine in these goats included mild to moderate salivation, depressed respiratory rate, decreased rectal temperature, bradycardia and hyperglycaemia. Plasma concentrations of total protein, sodium, potassium and chloride were not affected.     

Pharmacokinetics and pharmacodynamics of oral acetaminophen in combination with codeine in healthy Greyhound dogs

The purpose of this study was to determine the pharmacokinetic and antinociceptive effects of an acetaminophen/codeine combination administered orally to six healthy greyhounds. Antinociception was assessed using an electronic von Frey (vF) device as a mechanical/pressure model. Acetaminophen was administered at a dose of 600 mg (14.4–23.1 mg/kg) and codeine phosphate at 90 mg (2.1–3.3 mg/kg) equivalent to 67.5 mg codeine base (1.6–2.5 mg/kg). The geometric mean maximum plasma concentrations of acetaminophen, codeine, and codeine‐6‐glucuronide were 7.95 μg/mL, 11.0 ng/mL, and 3819 ng/mL, respectively. Morphine concentrations were <1 ng/mL. The terminal half‐lives of acetaminophen, codeine, and codeine‐6‐glucuronide were 0.94, 1.71, and 3.12 h. There were no significant changes in vF thresholds, except at 12 h which decreased on average by 17% compared to baseline. The decrease in vF thresholds at 12 h could be due to aversion, hyperalgesia, or random variability. The lack of antinociception in this study could be due to a true lack of antinociception, lack of model sensitivity, or specificity. Further studies using different models (including clinical trials), different dog breeds, multiple dose regimens, and a range of dosages are needed prior to recommended use or concluding lack of efficacy for oral acetaminophen/codeine in dogs.     

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.     

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.