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.     

Comparative cardiovascular, analgesic, and sedative effects of medetomidine, medetomidine-hydromorphone, and medetomidine-butorphanol in dogs

OBJECTIVE: To compare sedative, analgesic, and cardiopulmonary effects after IV administration of medetomidine (20 microg/kg), medetomidine-hydromorphone (20 microg of medetomidine/kg and 0.1 mg of hydromorphone/kg), and medetomidine-butorphanol (20 microg of medetomidine/kg and 0.2 mg of butorphanol tartrate/kg) in dogs. ANIMALS: 6 dogs healthy mixed-breed dogs. PROCEDURE: Instruments were surgically inserted, and heart rate (HR), respiratory rate (RR), systolic arterial pressure (SAP), mean arterial pressure (MAP), diastolic arterial pressure (DAP), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), core body temperature, and cardiac output (CO) were measured 0, 5, 10, 15, 30, 45, and 60 minutes after injection. Cardiac index (CI), stroke volume (SV), stroke index (SI), systemic vascular resistance (SVR), and pulmonary vascular resistance (PVR) were calculated. Arterial samples for blood gas analysis were collected 0, 15, and 45 minutes after injection. Intensity of analgesia, degree of sedation, and degree of muscle relaxation were evaluated at aforementioned time points and 75, 90, 120, 150, 180, and 210 minutes after injection. RESULTS: Administration of medetomidine, medetomidine-hydromorphone, and medetomidine-butorphanol was associated with increases in SAP, MAP, DAP, MPAP, PCWP, CVP, SVR, PVR, core body temperature, and PaCO2 and decreases in HR, CO, CI, SV, SI, RR, pH, and PaO2. Clinically important differences were not detected among treatments. Medetomidine-hydromorphone and medetomidine-butorphanol provided a longer duration of sedation and better quality of analgesia, compared with medetomidine alone. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine-hydromorphone or medetomidine-butorphanol is associated with improved analgesia and sedation but has cardiopulmonary effects comparable to those for medetomidine alone.     

Sedative and cardiorespiratory effects of three doses of romifidine in comparison with medetomidine in five cats

This study was designed to compare the effects of three doses of romifidine (200, 400 and 600 microg/kg) with medetomidine (80 microg/kg) administered intramuscularly to five cats. The quality of sedation and the cardiovascular and respiratory effects of each treatment were evaluated, and the onset and duration of the sedation, and the cats' recovery times, were measured. Cardiorespiratory variables were also analysed. The dose of 200 microg/kg romifidine was clinically superior to the other doses of romifidine, providing moderate sedation, with minor cardiorespiratory and other adverse effects. However none of the doses of romifidine induced as deep and reliable sedation as the dose of medetomidine.     

Sedative and analgesic effects of medetomidine in beagle dogs infected and uninfected with heartworm

The sedative and analgesic effects of medetomidine were evaluated in heartworm-infected (HW+) and uninfected (HW–) beagle dogs by intravenous (IV) and intramuscular (IM) administration of 30 µg/kg and 40 µg/kg doses, respectively. Posture, response to noise and the pedal reflex were monitored. A procedure for mock radiographic positioning was performed to evaluate its overall clinical use. Observation times were 0, 15, 30, 60, 90, 120 and 180 min. In addition, the times from injection until the dog could not stand on its feet (down time), from lateral to sternal recumbency (sternal recumbency time), and from sternal recumbency to rising again (rising time) were also noted.Medetomidine produced rapid sedation and analgesia by both routes. Down times for the IM and IV routes were similar, which verified the manufacturer's recommended doses. The HW+ dogs had shorter down times, probably owing to increased blood flow to the brain caused by adrenergic alpha-2 activity. Sternal recumbency and rising times did not differ between the groups, suggesting a similar metabolism. Sedation and analgesia were adequate for performing the procedure in all dogs. HW– dogs showed less resistance to handling during the procedure than HW+ dogs. Overall, medetomidine seems to be a suitable agent for short-term chemical restraint in dogs, even with subclinical heartworm infestation.     

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.     

Sedative and cardiorespiratory effects of acepromazine or atropine given before dexmedetomidine in dogs

To test the hypothesis that acepromazine could potentiate the sedative actions and attenuate the pressor response induced by dexmedetomidine, the effects of acepromazine or atropine were compared in six healthy adult dogs treated with this alpha2-agonist. In a randomised block design, the dogs received intravenous doses of either physiological saline, 0.05 mg/kg acepromazine or 0.04 mg/kg atropine, 15 minutes before an intravenous dose of 5 microg/kg dexmedetomidine. The dogs' heart rate was reduced by 50 to 63 per cent from baseline and their mean arterial blood pressure was increased transiently from baseline for 20 minutes after the dexmedetomidine. Atropine prevented the alpha2-agonist-induced bradycardia and increased the severity and duration of the hypertension, but acepromazine did not substantially modify the cardiovascular effects of the alpha2-agonist, except for a slight reduction in the magnitude and duration of its pressor effects. The dexmedetomidine induced moderate to intense sedation in all the treatments, but the dogs' sedation scores did not differ among treatments. The combination of acepromazine with dexmedetomidine had no obvious advantages in comparison with dexmedetomidine alone, but the administration of atropine before dexmedetomidine is contraindicated because of a severe hypertensive response.     

Effects of medetomidine and medetomidine-butorphanol combination on Schirmer tear test 1 readings in dogs

Medetomidine is a commonly used sedative in veterinary medicine whether administered alone or in combination with an opioid such as butorphanol. There are no previous studies that look at the effects of this drug on sequential Schirmer tear test (STT) 1 readings in dogs, including effects on tear production after reversal of the drug. The present study looked at two groups of 10 dogs each that were sedated with intravenous medetomidine or a combination of medetomidine and butorphanol. All dogs had tear readings taken presedation, 15 min postsedation, and 15 min after reversal of medetomidine with atipamezole. Results revealed that intravenous sedation with medetomidine and medetomidine-butorphanol in dogs with no history of ophthalmic disease and presedation STT 1 readings above 15 mm/min, causes a significant decrease in tear production that is measurable at 15 min postsedation. Readings returned to near presedation values within 15 min postreversal in most cases. It is therefore recommended that all eyes be treated with a tear substitute from the time the sedative is given until at least 15 min after reversal.     

Sedative, analgesic and cardiorespiratory effects of romifidine in cats

OBJECTIVE: To evaluate the sedative, analgesic, and cardiorespiratory effects of intramascular (IM) romifidine in cats. STUDY DESIGN: Prospective, randomized experimental trial. ANIMALS: Ten healthy adult cats. METHODS: Romifidine (100, 200, and 400 microg kg(-1)) or xylazine (1 mg kg(-1)) was given IM in a cross-over study design. Heart rate (HR), respiratory rate (RR), rectal temperature (RT), hemoglobin saturation, oscillometric arterial pressure, and scores for sedation, muscle relaxation, position, auditory response, and analgesia were determined before and after drug administration. Time to recumbency, duration of recumbency, and time to recover from sedation were determined. Subjective evaluation and cardiorespiratory variables were recorded before and at regular intervals for 60 minutes after drug administration. RESULTS: Bradycardia developed in all cats that were given romifidine or xylazine. No other significant differences in physiologic parameters were observed from baseline values or between treatments. Increasing the dose of romifidine did not result in increased sedation or muscle relaxation. Cats given xylazine showed higher sedation and muscle relaxation scores over time. Analgesia scores were significantly higher after administration of romifidine (400 microg kg(-1)) and xylazine (1 mg kg(-1)) than after romifidine at 100 or 200 microg kg(-1). Duration of lateral recumbency was not significantly different between treatments; however, cats took longer to recover after administration of 400 micro g kg(-1) romifidine. CONCLUSIONS AND CLINICAL RELEVANCE: Bradycardia is the most important adverse effect after IM administration of romifidine at doses ranging from 100 to 400 microg kg(-1) or 1 mg kg(-1) of xylazine in cats. The sedative effects of romifidine at 200 microg kg(-1) are comparable to those of 1 mg kg(-1) of xylazine, although muscle relaxation and analgesia were significantly less with romifidine than with xylazine.     

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.     

Sedative and cardiorespiratory effects of intranasal atomized alfaxalone in Japanese White rabbits

ObjectiveTo investigate the sedative and cardiorespiratory effects of intranasal atomization (INA) of alfaxalone using a mucosal atomization device in Japanese White rabbits.Study designRandomized, prospective, crossover study.AnimalsA total of eight healthy female rabbits, weighing 3.6–4.3 kg and aged 12–24 months.MethodsEach rabbit was randomly assigned to four INA treatments administered 7 days apart: Control treatment, 0.15 mL 0.9% saline in both nostrils; treatment INA0.3, 0.15 mL 4% alfaxalone in both nostrils; treatment INA0.6, 0.3 mL 4% alfaxalone in both nostrils; treatment INA0.9, 0.3 mL 4% alfaxalone in left, then right, then left nostril. Sedation was scored 0–13 using a composite measure scoring system for rabbits. Simultaneously, pulse rate (PR), respiratory rate (f_R), noninvasive mean arterial pressure (MAP), peripheral hemoglobin oxygen saturation (SpO₂) and arterial blood gases were measured until 120 minutes. The rabbits breathed room air during the experiment and were administered flow-by oxygen when hypoxemia (SpO₂ <90% or PaO₂ <60 mmHg; 8.0 kPa) developed. Data were analyzed using the Fisher's exact test and the Friedman test (p < 0.05).ResultsNo rabbit was sedated in treatments Control and INA0.3. All rabbits in treatment INA0.9 developed loss of righting reflex for 15 (10–20) minutes [median (25th–75th percentile)]. Sedation score significantly increased from 5 to 30 minutes in treatments INA0.6 and INA0.9 with maximum scores of 2 (1–4) and 9 (9–9), respectively. f_R decreased in an alfaxalone dose-dependent manner and one rabbit developed hypoxemia in treatment INA0.9. No significant changes were observed in PR and MAP.Conclusions and clinical relevanceINA alfaxalone resulted in dose-dependent sedation and respiratory depression in Japanese White rabbits to values considered not clinically relevant. Further investigation of INA alfaxalone in combination with other drugs is warranted.     

Sedative effects of three doses of romifidine in comparison with medetomidine in cats

ObjectiveTo compare the sedative effects of three doses of romifidine with one dose of medetomidine.Study designProspective blinded experimental cross-over.AnimalsFive adult Domestic Short Hair cats.MethodsCats were administered romifidine at 80, 120 and 160 μg kg^?1 or medetomidine at 20 μg kg^?1 (M20) intramuscularly (IM). Sedative effects were assessed for 3 hours by summing the scores given to posture, auditory response, resistance to positioning, muscular relaxation, and response to noxious stimuli, giving a total sedation score (TS). The area under the curve (AUC) of TS ≥7 (the score considered as clinically useful sedation) was calculated. Times to stages of sedation were determined. Some physiological parameters were measured. Data to compare treatments were analysed by anova or Kruskal–Wallis test as relevant.ResultsAll treatments gave a TS considered clinically useful. There were no significant differences between treatments for times to onset of sedation, maximum TS reached, or AUC. Differences between romifidine treatments for other sedation parameters were not significant but the time to maximum TS and to recovery was shortest in M20. Heart rate (HR) fell significantly with all treatments and, although with M20 it recovered at 65 minutes, it remained significantly depressed for 3 hours after all romifidine treatments. Most cats vomited, and/or hypersalivated after all treatments.ConclusionsDoses of 80, 120 and 160 μg kg^?1 romifidine IM produce sedation in cats which is similar to that following medetomidine 20 μg kg^?1. Recovery from sedation and of physiological parameters was quickest after M20.Clinical relevanceDoses of romifidine considerably lower than those investigated by previous authors give a clinically useful level of sedation, and their use might result in less side effects and a quicker recovery.     

A comparison of anesthetic and cardiorespiratory effects of tiletamine-zolazepam-butorphanol and tiletamine-zolazepam-butorphanol- medetomidine in cats

Using a randomized crossover design, this study compared the anesthetic and cardiorespiratory effects of three intramuscular anesthetic combinations in seven 2-year-old cats: tiletamine-zolazepam (8 mg/kg) and butorphanol (0.2 mg/kg) (TT); tiletamine-zolazepam (3 mg/kg), butorphanol (0.15 mg/kg), and medetomidine (15 microg/kg) (TTD); or the TTD protocol plus atipamezole (75 microg/kg IM) given 20 minutes later to reverse medetomidine. Analgesia was assessed using algometry and needle pricking. All three combinations effectively induced anesthesia suitable for orotracheal intubation within 5 minutes after injection. Hemoglobin oxygen saturation was lower than 90% at least once in all three groups between 5 and 15 minutes after drug administration. Blood pressure and heart and respiratory rates were within normal ranges. Both TT and TTD appeared to be effective injectable anesthetic combinations. TTD provided significantly better analgesia with a longer duration than did TT. Atipamezole administration shortened the duration of analgesia and decreased blood pressure but did not shorten total recovery time.     

Cardiopulmonary effects of medetomidine, oxymorphone, or butorphanol in selegiline-treated dogs

OBJECTIVES: To determine if chronic selegiline HCl administration affects the cardiopulmonary response to medetomidine, oxymorphone, or butorphanol in dogs. STUDY DESIGN: Prospective randomized experimental study. ANIMALS: Twenty-eight adult, random source, hound dogs weighing 21-33 kg. METHODS: Dogs were assigned to the following treatment groups: selegiline + medetomidine (MED; n = 6); placebo + MED (n = 6), selegiline + oxymorphone (OXY; n = 6); placebo + OXY (n = 6); selegiline + butorphanol (BUT; n = 7) or placebo + BUT (n = 6). Nine dogs were treated with two of the three pre-medicants. Dogs were treated with selegiline (1 mg kg(-1) PO, q 24 hours) or placebo for at least 44 days prior to pre-medicant administration. On the day of the experiment, arterial blood for blood gas analysis, blood pressure measurements, ECG, cardiac ultrasound (mM-mode, 2-D, and continuous wave Doppler), and behavioral observations were obtained by blinded observers. An IV injection of MED (750 micro g m(-2)), OXY (0.1 mg kg(-1)) or BUT (0.4 mg kg(-1)) was given. Cardiopulmonary and behavioral data were collected at 1, 2, 5, 15, 30, and 60 minutes after injection. RESULTS: Selegiline did not modify responses to any of the pre-medicant drugs. Medetomidine caused a significant decrease in heart rate (HR), cardiac output (CO), and fractional shortening (FS). Mean arterial pressure (MAP), systemic vascular resistance (SVR), and central venous pressure (CVP) were increased. Level of consciousness and resistance to restraint were both decreased. Oxymorphone did not affect MAP, CO, CVP, or SVR, but RR and PaCO(2) were increased. Level of consciousness and resistance to restraint were decreased. BUT decreased heart rate at 1 and 5 minutes. All other cardiovascular parameters were unchanged. BUT administration was associated with decreased arterial pH and increased PaCO(2). BUT decreased level of consciousness and resistance to restraint. CONCLUSIONS AND CLINICAL RELEVANCE: Although pre-medicants themselves altered cardiopulmonary and behavioral function, selegiline did not affect the response to medetomidine, oxymorphone, or butorphanol in this group of normal dogs.     

Cardiorespiratory effects of a combination of medetomidine, midazolam, and butorphanol in dogs.

OBJECTIVE: To characterize cardiorespiratory effects for a combination of medetomidine, butorphanol, and midazolam and to compare magnitude of cardiorespiratory depression with that induced by a commonly used inhalation anesthetic regimen (acepromazine-butorphanol-thiopental-halothane). ANIMALS: 10 clinically normal dogs (2 groups of 5). PROCEDURE: In treated dogs, medetomidine was administered (time, 0 minutes); midazolam and butorphanol were administered when effects of medetomidine were maximal (time, 20), and atipamezole was administered subsequently (time 60). In control dogs, drugs were administered after allowing effects of each agent to be achieved: acepromazine was given at time 0, butorphanol and thiopental were administered at time 35, and halothane was administered from time 45 until 110. Various cardiorespiratory and hematologic variables were measured or calculated. RESULTS: Respiratory rate, arterial and venous pH, venous oxygen content, oxygen consumption, and oxygen delivery decreased significantly below baseline values for treated dogs; end-tidal CO2, arterial and venous P(CO)2, and O2 extraction increased significantly above baseline values. Compared with data obtained after anesthesia, arterial HCO3- concentration, venous P(O2) and S(O2), cardiac output, oxygen extraction, and oxygen delivery appeared more modified in treated dogs. Oxygen consumption and physiologic shunt fraction were less modified in treated dogs than control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine-butorphanol-midazolam combination induced respiratory depression, comparable in magnitude to that induced by a widely used inhalation anesthetic regimen. Respiratory variables remained within acceptable limits during anesthesia; however, those associated with cardiovascular function were more severely affected.     

Echocardiographic evaluation of the effects of medetomidine and xylazine in dogs

The echocardiographic effects of medetomidine and xylazine were evaluated in 6 healthy dogs. Values for echocardiographic variables were significantly different from pre-treatment values after administration of both drugs. The effects of medetomidine were similar to that of xylazine. Because of their cardiac depressant effects, both drugs should be used with care in sick dogs.     

Sedative and physiologic effects of low-dose intramuscular alfaxalone in dogs

Objective

To describe the sedative and physiologic effects of two doses of alfaxalone administered intramuscularly in dogs.