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.     

Effects of preoperative administration of ketoprofen on whole blood platelet aggregation,buccal mucosal bleeding time,and hematologic indices in dogs undergoing elective ovariohysterectomy

OBJECTIVE: To determine effects of preoperative administration of ketoprofen on whole blood platelet aggregation, buccal mucosal bleeding time, and hematologic indices in dogs after elective ovariohysterectomy. DESIGN: Randomized, masked clinical trial. ANIMALS: 22 healthy dogs. PROCEDURE: 60 minutes before induction of anesthesia, 11 dogs were given 0.9% NaCl solution (control), and 11 dogs were given ketoprofen (2 mg/kg [0.9 mg/lb], IM). Thirty minutes before induction of anesthesia, glycopyrrolate (0.01mg/kg [0.005 mg/lb]), acepromazine (0.05 mg/kg [0.02 mg/lb]), and butorphanol (0.2 mg/kg 10.09 mg/lb]) were given IM to all dogs. Anesthesia was induced with thiopental (5 to 10 mg/kg [2.3 to 4.5 mg/lb], IV) and maintained with isoflurane (1 to 3%). Ovariohysterectomy was performed and butorphanol (0.1 mg/kg [0.05 mg/lb], IV) was given 15 minutes before completion of surgery. Blood samples for measurement of variables were collected at intervals before and after surgery. RESULTS: In dogs given ketoprofen, platelet aggregation was decreased 95 +/- 10% and 80 +/- 35% (mean +/- SD) immediately after surgery and 24 hours after surgery, respectively, compared with preoperative values. At both times, mean values in dogs given ketoprofen differed significantly from those in control dogs. Significant differences between groups were not observed for mucosal bleeding time or hematologic indices. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative administration of ketoprofen inhibited platelet aggre gation but did not alter bleeding time. Ketoprofen can be given before surgery to healthy dogs undergoing elective ovariohysterectomy, provided that dogs are screened for potential bleeding problems before surgery and monitored closely after surgery.     

Cardiorespiratory responses and plasma cortisol concentrations in dogs treated with medetomidine before undergoing ovariohysterectomy

OBJECTIVE: To evaluate effects of medetomidine on anesthetic dose requirements, cardiorespiratory variables, plasma cortisol concentrations, and behavioral pain scores in dogs undergoing ovariohysterectomy. DESIGN: Randomized, prospective study. ANIMALS: 12 healthy Walker-type hound dogs. PROCEDURE: Dogs received medetomidine (40 micrograms/kg [18.2 micrograms/lb] of body weight, i.m.; n = 6) or saline (0.9% NaCl) solution (1 ml, i.m.; 6) prior to anesthesia induction with thiopental; thiopental dose needed for endotracheal intubation was compared between groups. Ovariohysterectomy was performed during halothane anesthesia. Blood samples were obtained at various times before drug administration until 300 minutes after extubation. Various physiologic measurements and end-tidal halothane concentrations were recorded. RESULTS: In medetomidine-treated dogs, heart rate was significantly lower than in controls, and blood pressure did not change significantly from baseline. Plasma cortisol concentrations did not increase significantly until 60 minutes after extubation in medetomidine-treated dogs, whereas values in control dogs were increased from time of surgery until the end of the recording period. Control dogs had higher pain scores than treated dogs from extubation until the end of the recording period. CONCLUSION AND CLINICAL RELEVANCE: Administration of medetomidine reduced dose requirements for thiopental and halothane and provided postoperative analgesia up to 90 minutes after extubation. Dogs undergoing ovariohysterectomy by use of thiopental induction and halothane anesthesia benefit from analgesia induced by medetomidine administered prior to anesthesia induction. Additional analgesia is appropriate 60 minutes after extubation.     

Evaluation of sedative and cardiorespiratory effects of romifidine and romifidine-butorphanol in cats

OBJECTIVE: To determine sedative and cardiorespiratory effects of romifidine alone and romifidine in combination with butorphanol and effects of preemptive atropine administration in cats sedated with romifidine-butorphanol. DESIGN: Randomized crossover study. ANIMALS: 6 healthy adult cats. PROCEDURES: Cats were given saline (0.9% NaCl) solution followed by romifidine alone (100 microg/kg [45.4 microg/lb], i.m.), saline solution followed by a combination of romifidine (40 microg/kg [18.1 microg/lb], i.m.) and butorphanol (0.2 mg/kg [0.09 mg/lb], i.m.), or atropine (0.04 mg/kg [0.02 mg/lb], s.c.) followed by romifidine (40 microg/kg, i.m.) and butorphanol (0.2 mg/kg, i.m.). Treatments were administered in random order, with > or = 1 week between treatments. Physiologic variables were determined before and after drug administration. Time to recumbency, duration of recumbency, time to recover from sedation, and subjective evaluation of sedation, muscle relaxation, and analgesia were assessed. RESULTS: Bradycardia developed in all cats that received saline solution and romifidine-butorphanol or romifidine alone. Preemptive administration of atropine prevented bradycardia for 50 minutes in cats given romifidine-butorphanol. Oxyhemoglobin saturation was significantly decreased 10 minutes after romifidine-butorphanol administration in atropine-treated cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that administration of romifidine alone or romifidine-butorphanol causes a significant decrease in heart rate and that preemptive administration of atropine in cats sedated with romifidine-butorphanol effectively prevents bradycardia for 50 minutes.     

Postoperative hypoxemia and hypercarbia in healthy dogs undergoing routine ovariohysterectomy or castration and receiving butorphanol or hydromorphone for analgesia

OBJECTIVE: To determine frequency and severity of postanesthetic hypoxemia and hypercarbia in healthy dogs undergoing elective ovariohysterectomy or castration and given butorphanol or hydromorphone for analgesia. DESIGN: Prospective trial. ANIMALS: 0 healthy dogs weighing > 10 kg (22 lb). PROCEDURE: Dogs were anesthestized with acepromazine, glycopyrrolate, thiopental, and isoflurane, and butorphanol (n = 10) or hydromorphone (10) was used for perioperative analgesia. Arterial blood gas analyses were performed 10 and 30 minutes and 1, 2, 3, and 4 hours after extubation. RESULTS: In dogs that received hydromorphone, mean PaCO2 was significantly higher, compared with the preoperative value, 10 and 30 minutes and 1, 2, and 3 hours after extubation. Mean PaCO2 was significantly higher in dogs given hydromorphone rather than butorphanol 10 and 30 minutes and 1 and 2 hours after extubation. Mean PaO2 was significantly lower, compared with preoperative values, 30 minutes and 1 and 2 hours after extubation in dogs given hydromorphone and 30 minutes after extubation in dogs given butorphanol. Mean PaO2 was significantly lower in dogs given hydromorphone rather than butorphanol 1 hour after extubation. Four dogs had PaO2 < 80 mm Hg 1 or more times after extubation. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of hydromorphone to healthy dogs undergoing elective ovariohysterectomy or castration may result in transient increases in PaCO2 postoperatively and that administration of hydromorphone or butorphanol may result in transient decreases in PaO2. However, increases in PaCO2 and decreases in PaO2 were mild, and mean PaCO2 and PaO2 remained within reference limits.     

Effects of preoperative administration of ketoprofen on anesthetic requirements and signs of postoperative pain in dogs undergoing elective ovariohysterectomy

OBJECTIVE: To determine the effects of preoperative administration of ketoprofen on anesthetic requirements and signs of postoperative pain in dogs undergoing elective ovariohysterectomy. DESIGN: Randomized, controlled clinical trial. ANIMALS: 22 clinically normal client-owned dogs. PROCEDURE: 60 minutes before induction of anesthesia, 11 dogs were given ketoprofen (2 mg/kg [0.9 mg/lb], i.m.), and the other 11 were given saline (0.9% NaCl) solution. Dogs were premedicated with glycopyrrolate, acepromazine, and butorphanol and anesthetized with thiopental; anesthesia was maintained with isoflurane. Ovariohysterectomy was performed by an experienced surgeon, and butorphanol was given 15 minutes before completion of the procedure. Objective behavioral scores and numerical pain scores at rest and with movement were recorded every 2 hours for 12 hours after surgery and then every 4 hours for an additional 12 hours. RESULTS: Preoperative administration of ketoprofen did not reduce the dose of thiopental required to induce anesthesia or the end-tidal concentration of isoflurane required to maintain anesthesia. Activity levels and median objective behavioral scores were significantly higher 4 and 6 hours after surgery in dogs given ketoprofen than in dogs given saline solution. However, mean numerical pain scores in dogs given ketoprofen were not significantly different from scores for dogs given saline solution at any time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that preoperative administration of ketoprofen does not reduce anesthetic requirements in dogs undergoing elective ovariohysterectomy but may reduce signs of pain after surgery. Results also suggest that the objective behavioral score may be a more sensitive measure of acute postoperative pain than traditional numerical pain scores.     

Duration of nonresponse to noxious stimulation after intramuscular administration of butorphanol, medetomidine, or a butorphanol-medetomidine combination during isoflurane administration in dogs

OBJECTIVE: To assess duration of actions of butorphanol, medetomidine, and a butorphanol-medetomidine combination in dogs given subanesthetic doses of isoflurane (ISO). ANIMALS: 6 healthy dogs. PROCEDURE: Minimum alveolar concentration (MAC) values for ISO were determined. for each dog. Subsequently, 4 treatments were administered to each dog (saline [0.9% NaCl] solution, butorphanol [0.2 mg/kg of body weight], medetomidine [5.0 microg/kg], and a combination of butorphanol [0.2 mg/kg] and medetomidine [5.0 microg/kg]). All treatments were administered IM to dogs concurrent with isoflurane; treatment order was determined, using a randomized crossover design. Treatments were given at 7-day intervals. After mask induction with ISO and instrumentation with a rectal temperature probe, end-tidal CO2 and anesthetic gas concentrations were analyzed. End-tidal ISO concentration was reduced to 90% MAC for each dog. A tail clamp was applied 15 minutes later. After a positive response, 1 of the treatments was administered. Response to application of the tail clamp was assessed at 15-minute intervals until a positive response again was detected. RESULTS: Duration of nonresponse after administration of saline solution, butorphanol, medetomidine, and butorphanol-medetomidine (mean +/- SD) was 0.0+/-0.0, 1.5+/-1.5, 2.63+/-0.49, and 5.58+/-2.28 hours, respectively. Medetomidine effects were evident significantly longer than those for saline solution, whereas effects for butorphanol-medetomidine were evident significantly longer than for each agent administered alone. CONCLUSION AND CLINICAL RELEVANCE: During ISO-induced anesthesia, administration of medetomidine, but not butorphanol, provides longer and more consistent analgesia than does saline solution, and the combination of butorphanol-medetomidine appears superior to the use of medetomidine or butorphanol alone.     

The pharmacodynamics of thiopental, medetomidine, butorphanol and atropine in beagle dogs

This study evaluated the quality of anaesthesia and some of the haemodynamic effects induced by a combination of thiopental, medetomidine, butorphanol and atropine in healthy beagle dogs ( n  = 12). Following premedication with atropine (ATR, 0.022 mg/kg intravenously (i.v.)) and butorphanol (BUT, 0.22 mg/kg i.v.), medetomidine (MED, 22 μg/kg intramuscularly (i.m.)) was administered followed in 5 min by thiopental (THIO, 2.2 mg/kg i.v.). Heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MBP) were monitored continuously with an ECG and direct arterial blood pressure monitor. Atipamezole (ATI, 110 μg/kg i.v.) was administered to half of the dogs ( n  = 6) following surgery to evaluate the speed and quality of arousal from anaesthesia. Anaesthesia was characterized by excellent muscle relaxation, analgesia and absence of purposeful movement in response to surgical castration. Arousal following antagonism of mede­tomidine was significantly faster ( P  < 0.05) than in unantagonized dogs. Recoveries were smooth but recovery times following atipamezole administration were highly variable among dogs (sternal time range 6–38 min, standing time range 9–56 min). Medetomidine caused a significant ( P  < 0.05) increase in SBP, DBP and MBP. Atropine prevented the medetomidine induced bradycardia. In conclusion, this combination provided adequate surgical anaesthesia in healthy beagle dogs. At the dosages used in this study, it seems prudent that this combination should be reserved for dogs free of myocardial disease.     

Effects of butorphanol and carprofen on the minimal alveolar concentration of isoflurane in dogs

OBJECTIVE: To evaluate the effects of butorphanol and carprofen, alone and in combination, on the minimal alveolar concentration (MAC) of isoflurane in dogs. DESIGN: Randomized complete-block crossover study. ANIMALS: 6 healthy adult dogs. PROCEDURE: Minimal alveolar concentration of isoflurane was determined following administration of carprofen alone, butorphanol alone, carprofen and butorphanol, and neither drug (control). Anesthesia was induced with isoflurane in oxygen, and MAC was determined by use of a tail clamp method. Three hours prior to induction of anesthesia, dogs were fed a small amount of canned food without any drugs (control) or with carprofen (2.2 mg/kg of body weight [1 mg/lb]). Following initial determination of MAC, butorphanol (0.4 mg/kg [0.18 mg/lb], i.v.) was administered, and MAC was determined again. Heart rate, respiratory rate, indirect arterial blood pressure, endtidal partial pressure of CO2, and saturation of hemoglobin with oxygen were recorded at the time MAC was determined. RESULTS: Mean +/- SD MAC of isoflurane following administration of butorphanol alone (1.03 +/- 0.22%) or carprofen and butorphanol (0.90 +/- 0.21%) were significantly less than the control MAC (1.28 +/- 0.14%), but MAC after administration of carprofen alone (1.20 +/- 0.13%) was not significantly different from the control value. The effects of carprofen and butorphanol on the MAC of isoflurane were additive. There were not any significant differences among treatments in regard to cardiorespiratory data. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of butorphanol alone or in combination with carprofen significantly reduces the MAC of isoflurane in dogs; however, the effects of butorphanol and carprofen are additive, not synergistic.     

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.     

Analgesic efficacy of preoperative administration of meloxicam or butorphanol in onychectomized cats

OBJECTIVE: To determine analgesic efficacy and adverse effects of preemptive administration of meloxicam or butorphanol in cats undergoing onychectomy or onychectomy and neutering. DESIGN: Randomized controlled study. ANIMALS: 64 female and 74 male cats that were 4 to 192 months old and weighed 1.09 to 705 kg (2.4 to 15.5 lb). PROCEDURE: Cats received meloxicam (0.3 mg/kg [0.14 mg/lb], s.c.) or butorphanol (0.4 mg/kg [0.18 mg/lb], s.c.) 15 minutes after premedication and prior to anesthesia. A single blinded observer measured physiologic variables, assigned analgesia and lameness scores, and withdrew blood samples for each cat at baseline and throughout the 24 hours after surgery. Rescue analgesia (butorphanol, 0.4 mg/kg, i.v. or s.c.) or administration of acepromazine (0.025 to 0.05 mg/kg [0.011 to 0.023 mg/lb], i.v.) was allowed. RESULTS: Meloxicam-treated cats were less lame and had lower pain scores. Cortisol concentration was higher at extubation and lower at 1, 5, and 12 hours in the meloxicam-treated cats. Fewer meloxicam-treated cats required rescue analgesia at 3, 5, 12, and 24 hours after extubation. General impression scores were excellent or good in 75% of meloxicam-treated cats and 44% of butorphanol-treated cats. There was no treatment effect on buccal bleeding time; PCV and BUN concentration decreased in both groups, and glucose concentration decreased in meloxicam-treated cats. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative administration of meloxicam improved analgesia for 24 hours without clinically relevant adverse effects in cats that underwent onychectomy or onychectomy and neutering and provided safe, extended analgesia, compared with butorphanol.     

Enhancing effect of butorphanol on medetomidine-induced sedation in pigs.

Enhancing effect of an opiate agonist-antagonist butorphanol (0.2 mg/kg) on sedation induced by medetomidine (80 micrograms/kg) was evaluated in pigs. Butorphanol significantly enhanced the depth of medetomidine-induced sedation and prolonged the duration of that assessed by posture score and spontaneous movement of pigs. The combination of medetomidine and butorphanol produced excellent muscle relaxation and moderate surface analgesia which was enough for procedures with mild pain in pigs.     

Evaluation of the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication

OBJECTIVE: To compare the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication. ANIMALS: 42 client-owned dogs that underwent elective ovariohysterectomy. PROCEDURE: Each dog was randomly allocated to receive medetomidine and butorphanol tartrate (20 microgram/kg and 0.2 mg/kg, respectively, IM) or acepromazine maleate and butorphanol (0.05 and 0.2 mg/kg, respectively, IM) for preanesthetic medication. Approximately 80 minutes later, anesthesia was induced by administration of propofol and maintained by use of isoflurane in oxygen. Each dog was also given carprofen before surgery and buprenorphine after surgery. Plasma concentrations of epinephrine, norepinephrine, cortisol, and beta-endorphin were measured at various stages during the perioperative period. In addition, cardiovascular and clinical variables were monitored. RESULTS: Concentrations of epinephrine, norepinephrine, and cortisol were significantly lower for dogs administered medetomidine. Concentrations of beta-endorphin did not differ between the 2 groups. Heart rate was significantly lower and mean arterial blood pressure significantly higher in dogs administered medetomidine, compared with values for dogs administered acepromazine. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that for preanesthetic medications, medetomidine may offer some advantages over acepromazine with respect to the ability to decrease perioperative concentrations of stress-related hormones. In particular, the ability to provide stable plasma catecholamine concentrations may help to attenuate perioperative activation of the sympathetic nervous system.     

Comparison of the efficacy and cardiorespiratory effects of medetomidine-based anesthetic protocols in ring-tailed lemurs (Lemur catta).

The relative efficacies and cardiorespiratory effects of three injectable anesthetic combinations containing medetomidine were evaluated in ring-tailed lemurs (Lemur catta). In addition, the direct effects of medetomidine on heart rate and blood pressure were evaluated in lemurs anesthetized with isoflurane. For injectable anesthesia, captive adult ring-tailed lemurs were anesthetized with medetomidine and ketamine (0.04-0.06 mg/kg, i.m. and 3 mg/kg, i.m., respectively), medetomidine, butorphanol, and ketamine (0.04 mg/kg, i.m., 0.4 mg/kg, i.m., and 3 mg/kg, i.m., respectively), or medetomidine, butorphanol, and midazolam (0.04 mg/kg, i.m., 0.4 mg/kg, i.m., and 0.3 mg/kg, i.m., respectively). For inhalation anesthesia, lemurs were mask-induced and maintained with isoflurane for 30 min before receiving medetomidine (0.04 mg/kg, i.m.). Sedation produced by medetomidine-ketamine was unpredictable and of short duration. Both medetomidine-butorphanol-ketamine (MBK) and medetomidine-butorphanol-midazolam (MBMz) provided adequate anesthesia for routine physical exams; however, the effects of MBMz lasted longer than those of MBK. Heart rates and respiratory rates were within clinically normal ranges for all groups, and lemurs remained normotensive throughout the study. Common side effects such as hypertension and bradycardia associated with the use of alpha2-adrenergic receptor agonist combinations in other species were not observed. Likewise, medetomidine administration had no effect on HR in lemurs receiving isoflurane. Lemurs in all groups were well ventilated and remained well oxygenated throughout the procedures, though arterial partial pressure of O2 was lowest in the MBMz group. All three injectable medetomidine combinations were effective in ring-tailed lemurs but only MBK and MBMz provided adequate depth and duration of anesthesia for use as sole regimes. For many clinical procedures in lemurs, MBMz offers advantages over MBK because of its longer duration of action and its rapid and more complete reversibility with specific antagonists.     

Development of a minimum-anesthetic-concentration depression model to study the effects of various analgesics in goldfish (Carassius auratus)

Teleost fish demonstrate the neurophysiologic capacity to experience pain and analgesia. A common model for assessing analgesic effect is the reduction of minimum anesthetic concentration (MAC). The present study adapted the model of MAC depression to evaluate the analgesic effects of morphine, butorphanol, medetomidine, and ketoprofen in goldfish (Carassius auratus). MAC was determined by an up-down method of sequential population sampling, anesthetizing fish with tricaine methanesulfonate (MS-222) in concentration increments of 10 parts per million (ppm), and using intramuscular needle insertion as a supramaximal noxious stimulus. Baseline MAC was determined in triplicate at the beginning (MACi) and conclusion (MACe) of the experiment (approximately 60 days). For drug trials, MAC was redetermined 1 hr after administration of morphine (10, 20, 40 mg/kg i.m.), butorphanol (0.1, 0.2, 0.4 mg/kg i.m.), medetomidine (0.01, 0.015, 0.025 mg/kg i.m.), ketoprofen (0.5, 1.0, 2.0 mg/kg i.m.), or saline control. Each drug/dose was tested in random order with a > 6-day washout period. MACi and MACf were 163 and 182 ppm, respectively, and were significantly different from each other (P = 0.02). All doses of morphine and ketoprofen decreased MAC below MACi. The highest dose of medetomidine decreased MAC below MACi. The lowest dose of butorphanol decreased MAC below MACi, but higher doses increased MAC above MACf. The authors conclude that MAC determination in fish using MS-222 was feasible and reproducible in the short term. The fact that MAC increased over time and/or exposure may limit the usefulness of MS-222 in MAC depression studies. Morphine and ketoprofen decrease anesthetic needs in goldfish and may provide analgesia.     

Clinical evaluation of medetomidine, a novel sedative and analgesic drug for dogs and cats

Medetomidine, a potent alpha 2-adrenoceptor agonist, was investigated in open, multicenter clinical trials with patients of various canine and feline breeds (1736 dogs and 678 cats). The purpose of the study was to find an optimal dose of medetomidine for sedation and analgesia in clinical practice and to study how well the intended procedure could be performed under the influence of the drug. The mean dose (i.m.) of medetomidine used for examinations, clinical procedures and minor surgical interventions was 40 micrograms/kg, and for radiography 30 micrograms/kg. In cats the dose was 80-110 micrograms/kg. On the doses chosen, almost all animals were recumbent and 72% of the dogs and 85% of the cats were in a slight anaesthetic stage, unable to rise. The evaluation of the overall suitability of medetomidine (% of cases) in different indications was "very satisfactory" or "satisfactory" in 95% of dogs and 81-96% of cats. Side effects reported were limited almost exclusively to vomiting and muscle jerking in dogs (12% and 0.5% of the cases) and to vomiting in cats (65%). Medetomidine seems to suffice for pharmacological restraint of dogs and cats. The concomitant use of medetomidine (80-100 micrograms/kg) and ketamine (7 mg/kg) in cats (n = 295) provided a good anaesthesia (20-40 min). The recovery was smooth. The present study shows that medetomidine provides an effective level of sedation and analgesia for clinical use.     

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.     

Comparison of medetomidine and dexmedetomidine as premedicants in dogs undergoing propofol-isoflurane anesthesia.

OBJECTIVE: To compare 3 dose levels of medetomidine and dexmedetomidine for use as premedicants in dogs undergoing propofol-isoflurane anesthesia. ANIMALS: 6 healthy Beagles. PROCEDURE: Dogs received medetomidine or dexmedetomidine intravenously at the following dose levels: 0.4 microg of medetomidine or 0.2 microg of dexmedetomidine/kg of body weight (M0.4/D0.2), 4.0 microg of medetomidine or 2.0 microg of dexmedetomidine/kg (M4/D2), and 40 microg of medetomidine or 20 microg of dexmedetomidine/kg (M40/D20). Sedation and analgesia were scored before induction. Anesthesia was induced with propofol and maintained with isoflurane. End-tidal isoflurane concentration, heart rate, and arterial blood pressures and gases were measured. RESULTS: Degrees of sedation and analgesia were significantly affected by dose level but not drug. Combined mean end-tidal isoflurane concentration for all dose levels was higher in dogs that received medetomidine, compared with dexmedetomidine. Recovery time was significantly prolonged in dogs treated at the M40/D20 dose level, compared with the other dose levels. After induction, blood pressure decreased below reference range and heart rate increased in dogs treated at the M0.4/D0.2 dose level, whereas blood pressure was preserved in dogs treated at the M40/D20 dose level. However, dogs in these latter groups developed profound bradycardia and mild metabolic acidosis during anesthesia. Treatment at the M4/D2 dose level resulted in more stable cardiovascular effects, compared with the other dose levels. In addition, PaCO2 was similar among dose levels. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine is at least as safe and effective as medetomidine for use as a premedicant in dogs undergoing propofol-isoflurane anesthesia.     

Reversible anesthesia of captive California sea lions (Zalophus californianus) with medetomidine, midazolam, butorphanol, and isoflurane.

Two adult California sea lions (Zalophus californianus) were effectively anesthetized 13 times with medetomidine (0.010-0.013 mg/kg), midazolam (0.2-0.26 mg/kg), and butorphanol (0.2-0.4 mg/kg) by i.m. hand or pole syringe injection. For each anesthetic event, atropine (0.02 mg/kg, i.m.) was administered 6-20 min after initial injections, and oxygen administration via face mask or nasal insufflation began at the same time. Light anesthesia was induced in 8-22 min and lasted 13-78 min. During eight of the procedures, isoflurane (0.5-2.0%) was administered via face mask or endotracheal tube for an additional 30-120 min to facilitate longer procedures or surgery. Anesthesia was antagonized with atipamezole (0.05-0.06 mg/kg) and naltrexone (0.1 mg/kg) in seven events, with the addition of flumazenil (0.0002-0.002 mg/kg) in six events. The antagonists were administered by i.m. injection 42-149 min after administration of the induction agents. All sea lions recovered to mild sedation within 4-17 min after administration of the antagonists.     

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.