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Comparison of anesthetic and cardiorespiratory effects of diazepam-butorphanol-ketamine, acepromazine-butorphanol-ketamine, and xylazine-butorphanol-ketamine in ferrets.

Ten ferrets were used in a crossover study to determine the sedative effects of intramuscularly administered diazepam (3 mg/kg body weight)-butorphanol (0.2 mg/kg body weight)-ketamine (15 mg/kg body weight); acepromazine (0.1 mg/kg body weight)-butorphanol (0.2 mg/kg body weight)-ketamine (15 mg/kg body weight); and xylazine (2 mg/kg body weight)-butorphanol (0.2 mg/kg body weight)-ketamine (15 mg/kg body weight). All of the ferrets became laterally recumbent following the administration of each drug combination. The xylazine-butorphanol-ketamine combination induced significantly longer (p less than 0.05) durations of tail-clamp analgesia (mean+/-standard deviation [SD], 81.0+/-19.1 min versus 20.5+/-25.4 min and 30.0+/-26.9 min), dorsal recumbency (mean+/-SD, 94.6+/-13.6 min versus 75. 6+/-34.7 min and 55.2+24.8 min), and muscle relaxation suitable for endotracheal intubation (mean+/-SD, 67.1+/-23.0 min versus 7.0+/-22.1 min and 9.5+/-15.4 min) than the diazepam-butorphanol-ketamine and acepromazine-butorphanol-ketamine combinations, respectively. The recovery time from dorsal recumbency to standing was not significantly different among the three treatment groups. The heart rate was significantly lower in the xylazine-butorphanol-ketamine group; however, systolic blood pressure was not significantly different among the treatment groups. Ventilatory function was more depressed in the diazepam-butorphanol-ketamine and xylazine-butorphanol-ketamine groups than in the acepromazine-butorphanol-ketamine group. A period (approximately 45 minutes) of hypoxia was observed in the xylazine-butorphanol-ketamine-treated ferret. Of the three combinations evaluated in ferrets, xylazine-butorphanol-ketamine was concluded to be the most effective anesthetic combination. However, hypoxemia and ventricular arrhythmias were observed in the xylazine-butorphanol-ketamine-treated ferrets, so the effectiveness of the xylazine-butorphanol-ketamine combination should be weighed against its cardiorespiratory side effects.

Acepromazine↗

Evaluation of sedative and cardiorespiratory effects of diazepam-butorphanol, acepromazine-butorphanol, and xylazine-butorphanol in ferrets.

Ten ferrets were used in a crossover study to determine the sedative effects of intramuscularly (IM) administered diazepam (3 mg/kg body weight)-butorphanol (0.2 mg/kg body weight), acepromazine (0.1 mg/kg body weight)-butorphanol (0.2 mg/kg body weight), or xylazine (2.0 mg/kg body weight)-butorphanol (0.2 mg/kg body weight). All ferrets became laterally recumbent following the administration of each drug combination. The xylazine-butorphanol combination caused a significantly longer (p less than 0.05) duration of analgesia than the diazepam-butorphanol and acepromazine-butorphanol combinations. None of the ferrets could be intubated with any of the drug combinations. The time from induction to recovery was significantly shorter in the acepromazine-butorphanol-treated ferrets. A significantly lower heart rate was observed in the xylazine-butorphanol-treated ferrets; however, an acceptable systolic blood pressure was maintained. Ventilatory function was more depressed in the diazepam-butorphanol- and xylazine-butorphanol-treated ferrets than in the acepromazine-butorphanol-treated ferrets. Xylazine-butorphanol was found to be the best combination for use in ferrets.

Acepromazine↗

Cardiorespiratory effects of medetomidine-butorphanol, medetomidine-butorphanol-diazepam, and medetomidine-butorphanol-ketamine in captive red wolves (Canis rufus).

Safe, effective, and reversible immobilization protocols are essential for the management of free-ranging red wolves (Canis rufus). Combinations using an alpha2-adrenoceptor agonist and ketamine have been shown to be effective for immobilization but are not reversible and can produce severe hypertension and prolonged or rough recoveries. To minimize hypertension and provide reversibility, 24 red wolves were immobilized using three medetomidine-butorphanol (MB) combinations without the use of ketamine in the initial injection. All wolves were administered medetomidine (0.04 mg/kg i.m.) and butorphanol (0.4 mg/kg i.m.). Seven wolves received no other immobilization agents (MB wolves), nine received diazepam (0.2 mg/kg i.v.) at the time they were instrumented (MBD wolves), and eight received ketamine (1 mg/kg i.v.) 30 min after instrumentation (MBK30 wolves). Physiologic parameters were monitored during immobilization. The heart rate was similar among the three groups for the first 30 min, and marked bradycardia was noted in one wolf from each group. Hypertension was observed initially in all three groups but was resolved within 10-30 min. The MBK30 wolves had significant elevations in heart rate and transient hypertension after intravenous ketamine administration. Most wolves had mild to moderate metabolic acidemia. Immobilizing drugs were antagonized in all wolves with atipamezole (0.2 mg/kg i.m.) and naloxone (0.02 mg/kg i.m.). The medetomidine-butorphanol-diazepam wolves were also given flumazenil (0.04 mg/kg i.v.). All wolves were standing within 12 min and were fully recovered within 17 min. Medetomamine-butorphanol and MBD combinations provided effective and reversible immobilization of red wolves without the sustained hypertension associated with the use of alpha2-adrenoceptor agonist-ketamine combinations. Delaying the administration of ketamine reduced its hypertensive effects.

Adrenergic alpha-Antagonists↗

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.

Analgesics, Non-Narcotic↗

A pharmacokinetic interaction study between butorphanol and sumatriptan nasal sprays in healthy subjects: importance of the timing of butorphanol administration.

Sumatriptan and butorphanol nasal sprays are commonly used agents for the management of migraine headaches. Under certain circumstances, these two agents may be administered closely in time. However, the possibility of a pharmacokinetic interaction and the safety of this regime have not been examined. In this crossover design study, 24 healthy subjects received the following four treatments, each separated by at least 7 days: 1 mg butorphanol (Stadol NS7); 20 mg sumatriptan (Imitrex Nasal Spray); or both formulations together with butorphanol administered either 1 or 30 min after sumatriptan. Serial plasma samples were collected for 24 h post-dose and analysed for butorphanol and/or sumatriptan by HPLC-MS/MS. Butorphanol plasma concentrations were reduced when it was administered 1 min (mean 28.6% decrease in AUC(0-infinity)), but not 30 min, after sumatriptan. The pharmacokinetics of sumatriptan were not substantially altered by butorphanol. The combination of nasally administered sumatriptan and butorphanol appeared safe. However, if butorphanol nasal spray is administered <30 min after sumatriptan nasal spray, the analgesic effect of butorphanol may be diminished due to reduced nasal absorption resulting from probable transient vasoconstriction of nasal blood vessels by sumatriptan.

Administration, Intranasal↗

Comparison of epidural butorphanol plus clonidine with butorphanol alone for postoperative pain relief.

BACKGROUND: Epidural butorphanol has been shown to produce effective analgesia with less side effects than that of morphine but relatively short duration. Clonidine, an alpha 2-adrenergic agonist, has been reported to provide [corrected] pain relief by epidural administration. Furthermore, epidural clonidine has been shown to potentiate the analgesic effect of epidural morphine. The present study was undertaken to evaluate the analgesic and side effects of epidural administration (Ep) of butorphanol and clonidine. METHODS: After giving their consents, 60 adult patients scheduled for abdominal surgeries were enrolled in this study. Prior to anesthesia induction, indwelling lumbar epidural catheters were placed in all patients who then received general anesthesia with inhalation anesthetic without narcotic analgesics. In the postoperative period, when the patients first complained of pain, they were divided into 2 equal groups of 30 patients each in a randomized and double blinded fashion with Group I receiving Ep butorphanol 0.5 mg and Group II receiving Ep butorphanol 0.5 mg plus clonidine 75 micrograms. All patients were observed for pain relief, sedation, vital signs, arterial blood gas studies and adverse effects for 12 h. RESULTS: Onset of pain relief with epidural butorphanol began at 5 min and peaked at 20-30 min with a duration of action lasting 4-6 h. The combination of butorphanol and clonidine had numerically superior pain relief than that of butorphanol for the first 30 min but it did not attain statistical significant difference. The duration of action with the combination group was similar to that of butorphanol alone. Incidence of adverse effects were similar in both groups except that hypotension and more pronounced sedation were observed in Group II. CONCLUSIONS: Our study showed that the addition of clonidine to epidural butorphanol did not enhance its analgesic effect in any significant manner nor did it reduce the adverse effects. This combination does not seem to offer any advantage for clinical use.

Adrenergic alpha-Agonists↗

The influence of butorphanol dose on characteristics of xylazine-butorphanol-propofol anesthesia in horses at altitude.

OBJECTIVE: To characterize behavioral and physiological responses to short-term, unsupplemented intravenous (IV) anesthesia in healthy horses at high altitude (2240 m), and to test the hypothesis that the dose of butorphanol modifies the response of the horse to propofol anesthesia following xylazine pre-medication. STUDY DESIGN: Randomized prospective butorphanol dose cross-over experimental design. Animals Eight healthy horses, 13 +/- 6 (mean +/- SD) years of age, and weighing 523 +/- 26 kg. METHODS: Each horse was anesthetized three times with at least 3 weeks between each anesthesia. After collecting pre-drug data, xylazine (0.5 mg kg(-1)) was given IV. Five minutes later butorphanol was given IV according to a randomized order of three doses: 0.025, 0.05 and 0.075 mg kg(-1). Five minutes later, anesthesia was induced with propofol, 2 mg kg(-1) IV. Data on heart rate (HR) and respiratory rate (f(r)), mean arterial blood pressure, P(a)O(2), P(a)CO(2) and pH(a) were collected before, during and for 60 minutes following anesthesia, and quality of induction and recovery was scored. RESULTS: The pre-drug values for the three butorphanol groups did not differ. The combined pre-drug values from the 24 studies were HR, 33 +/- 7 beats minute(-1); f(r), 11 +/- 3 breaths minute(-1); P(a)O(2), 67 +/- 7 mmHg; P(a)CO(2), 36 +/- 4 mmHg; and pH(a), 7.42 +/- 0.04. Five minutes after anesthetic induction P(a)O(2) decreased and P(a)CO(2) increased 14.5 +/- 7.7 and 5.1 +/- 4.9 mmHg, respectively, but returned to pre-drug levels within 15 minutes of anesthetic recovery. There were no significant butorphanol dose-related differences in physiological results, anesthetic induction and recovery quality scores or recovery time. CONCLUSIONS AND CLINICAL RELEVANCE: Dose of butorphanol did not markedly influence study results. Notably, low P(a)O(2) values related to geographic location of study and general anesthesia indicates a narrow margin of error for hypoxemia-related complications in anesthetized horses breathing unsupplemented air at high altitude.

Altitude↗

Evaluation of the sedative and cardiorespiratory effects of medetomidine, medetomidine-butorphanol, medetomidine-ketamine, and medetomidine-butorphanol-ketamine in ferrets.

Ten ferrets were used in a crossover study to determine the anesthetic effects of intramuscular (I.M.) medetomidine (80 microg/kg body weight), medetomidine (80 microg/kg body weight)-butorphanol (0.1 mg/kg body weight), medetomidine (80 microg/kg body weight)-ketamine (5 mg/kg body weight), and medetomidine (80 microg/kg body weight)-butorphanol (0.1 mg/kg body weight)-ketamine (5 mg/kg body weight). All ferrets assumed lateral recumbency within four minutes and remained dorsally recumbent for 100 minutes, until atipamezole (400 microg/kg body weight, I.M.) administration. All four anesthetic combinations were effective for chemical restraint, with the most respiratory depression occurring in the medetomidine-butorphanol-ketamine group. The addition of butorphanol or ketamine to medetomidine significantly increased the duration of analgesia. The addition of ketamine to medetomidine-butorphanol expedited endotracheal intubation.

Analgesics, Opioid↗

The effect of a combination of medetomidine-butorphanol and medetomidine, butorphanol, atropine on glomerular filtration rate in dogs.

The effects of intramuscularly administered medetomidine and butorphanol (MB), and medetomidine, butorphanol, atropine (MBA) on glomerular filtration rate (GFR) were determined in six dogs as measured by 99m-Tc-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) nuclear scintigraphy. Direct systolic, diastolic, and mean arterial blood pressures and heart rate were measured at regular time intervals before, during, and after GFR calculations. The mean GFR measurement following MB was significantly greater (4.44 ml/min/kg) than following MBA (3.82 ml/min/kg) or saline treatment (3.41 ml/min/kg). There was no significant difference between the mean GFR measurements following MBA injection and following saline injection. Diastolic and mean arterial pressures following MBA injection were significantly higher than the values recorded after either MB or saline alone. Heart rate following MB administration was significantly lower than that recorded for dogs receiving MBA or saline alone. The results of this study indicate that the administration of medetomidine in combination with butorphanol significantly increases total GFR in healthy dogs, while the administration of the combination of medetomidine, butorphanol, and atropine does not.

Adrenergic alpha-Agonists↗

The use of propofol for induction of anaesthesia in dogs premedicated with acepromazine, butorphanol and acepromazine-butorphanol.

Cardiovascular, pulmonary and anaesthetic-analgesic responses were evaluated in 18 male and female dogs to determine the effect of the injectable anaesthetic propofol used in conjuction with acepromazine and butorphanol. The dogs were randomly divided into three groups. Dogs in Group A were premeditated with 0.1 mg/kg of intramuscular acepromazine followed by an induction dose of 4.4 mg/kg of intravenous propofol; Group B received 0.2 mg/kg of intramuscular butorphanol and 4.4 mg/kg of intravenous propofol; dogs in Group AB were administered a premeditation combination of 0.1 mg/kg of intramuscular acepromazine and 0.2 mg/kg of intramuscular butorphanol, followed by induction with 3.3 mg/kg of intravenous propofol. The induction dose of propofol was given over a period of 30-60 seconds to determine responses and duration of anaesthesia. Observations recorded in the dogs included heart and respiratory rates, indirect arterial blood pressures (systolic, diastolic and mean), cardiac rhythm, end-tidal CO, tension, oxygen saturation, induction time, duration of anaesthesia, recovery time and adverse reactions. The depth of anaesthesia was assessed by the response to mechanical noxious stimuli (tail clamping), the degree of muscle relaxation and the strength of reflexes. Significant respiratory depression was seen after propofol induction in both groups receiving butorphanol with or without acepromazine. The incidence of apnea was 4/6 dogs in Group B, and 5/6 dogs in Group AB. The incidence of apnea was also correlated to the rate of propofol administration. Propofol-mediated decreases in arterial blood pressure were observed in all three groups. Moderate bradycardia (minimum value > 55 beats/min) was observed in both Groups B and AB. There were no cardiac dysrhythmias noted in any of the 18 dogs. The anaesthetic duration and recovery times were longer in dogs premeditated with acepromazine/butorphanol.

Journal Article↗

Comparison of continuous brachial plexus infusion of butorphanol, mepivacaine and mepivacaine-butorphanol mixtures for postoperative analgesia.

We have reported recently that continuous administration of butorphanol into the brachial plexus sheath provided analgesia of a quality superior to that of continuous i.v. administration. In the present study, we have compared postoperative pain relief produced by continuous infusion of one of three types of solution into the axillary sheath: opioid alone, local anaesthetic alone or a mixture of local anaesthetic and opioid. In patients undergoing upper extremity surgery with continuous axillary brachial plexus block, we injected one of the three solutions into the axillary neurovascular sheath: butorphanol 2 mg (group B), 0.5% mepivacaine alone (group M) and 0.5% mepivacaine-butorphanol (group MB); the volume of each solution was 50 ml, administered at a rate of 50 ml per 24 h. At 3 h after operation, visual analogue scale (VAS) scores were significantly higher in group M than in group MB (P < 0.01), and higher in group B than in group MB (P < 0.05).

Adolescent↗

Comparison of sedative effects of medetomidine-midazolam, acepromazine-butorphanol and midazolam-butorphanol in dogs.

Sedative effects of medetomidine at 20 micrograms/kg and midazolam at 0.3 mg/kg (MM), acepromazine at 0.05 mg/kg and butorphanol at 0.2 mg/kg (AB), and midazolam at 0.1 mg/kg and butorphanol at 0.2 mg/kg (MB) were compared in dogs. All dogs given MM were laterally recumbent within 11 min of the administration of the drugs, and this combination also induced deep sedation accompanied by analgesia and muscle relaxation, and strongly depressed arousal reactions to external stimuli. However, undesirable effects such as bradycardia and decreased respiration were also observed in dogs given MM. Six of seven dogs given AB were laterally recumbent within 16 min of the administration of the drugs, and this combination induced relatively deep sedation but only a mild depression of arousal reactions to external stimuli. MB induced mild or moderate sedation with relatively large differences in effects among individuals. The recovery from sedation in each group was smooth and total recovery times were not significantly different.

Acepromazine↗

Comparison of cardiopulmonary effects of medetomidine-midazolam, acepromazine-butorphanol and midazolam-butorphanol in dogs.

Cardiopulmonary effects of intramuscular administration of medetomidine-midazolam at 20 micrograms/kg and 0.3 mg/kg, respectively (MM), acepromazine-butorphanol at 0.05 and 0.2 mg/kg, respectively (AB), and midazolam-butorphanol at 0.1 and 0.2 mg/kg, respectively (MB), were compared in dogs. MM produced relatively large cardiovascular changes such as bradycardia, hypertension, a decrease in cardiac output and vasoconstriction. AB produced moderate cardiovascular changes. Hypotension was observed within 5 min after administration and the mean arterial blood pressure decreased by 30% at 20 min after administration. MB produced decreases in arterial blood pressure and cardiac output, but these changes were small and, of the combinations evaluated in this study, MB had the mildest cardiovascular effects.

Acepromazine↗

Effects of midazolam-butorphanol, acepromazine-butorphanol and medetomidine on an induction dose of propofol and their compatibility in dogs.

The effects of acepromazine-butorphanol (AB), midazolam-butorphanol (MB) and medetomidine (Med) on the induction dose of propofol and their compatibility with propofol were evaluated in client-owned dogs. All premedications induced good to excellent sedation and the induction dose of propofol was considerably reduced. Of the tested premedicants, Med induced the deepest sedation and the most potent dose-sparing effect. Induction of anesthesia was excellent to good in all dogs except for one dog premedicated with MB. Most dogs premedicated with AB or MB showed temporary apnea. Although other adverse effects such as bradycardia or hypotension may also occur, premedication with MB, AB or Med is a valuable technique for the induction of anesthesia with propofol in dogs in a clinical setting.

Acepromazine↗

Comparison of the cardiorespiratory effects of medetomidine-butorphanol-ketamine and medetomidine-butorphanol-midazolam in patas monkeys (Erythrocebus patas).

The cardiorespiratory effects, effectiveness, and reversibility of two injectable anesthetic combinations were compared in captive patas monkeys (Erythrocebus patas). Seven patas monkeys were hand-injected with medetomidine (40 microg/kg, i.m.), butorphanol (0.4 mg/kg. i.m.), and ketamine (3.0 mg/kg. i.m.), and seven were injected with the same dosages of medetomidine and butorphanol plus midazolam (0.3 mg/kg, i.m.). Heart rates decreased in monkeys in both treatment groups and were lower than those previously recorded in patas monkeys anesthetized with either ketamine or ketamine and isoflurane. Mean arterial pressures were highest in ketamine-treated monkeys but remained within normal limits for both groups. End tidal CO2 values increased gradually over time in both groups and were above physiologic norms after 20 min. Respiratory rates were similar between groups and remained constant throughout the procedures. Despite adequate ventilation parameters, initial low percent oxygen-hemoglobin saturation (SpO2) values were suggestive of severe hypoxemia. It was not clear whether these were accurate readings or an artifact of medetomidine-induced peripheral vasoconstriction. Oxygen supplementation restored SpO2 values to normal (>94%) in both groups. Both combinations effectively produced a state of light anesthesia, although spontaneous recoveries occurred after 30 min in three ketamine-treated monkeys. All monkeys were given i.m. atipamezole (0.2 mg/kg) and naloxone (0.02 mg/kg), whereas midazolam-treated monkeys also received flumazenil (0.02 mg/kg, i.v.), which resulted in faster (median recovery time = 5 min) and more complete recoveries in this group. Both combinations are safe to use when supplemented with oxygen, although the midazolam combination provided a longer anesthetic period and was more fully reversible.

Analgesics, Opioid↗

Effects of medetomidine-midazolam, acepromazine-butorphanol, and midazolam-butorphanol on induction dose of thiopental and propofol and on cardiopulmonary changes in dogs.

OBJECTIVE: To evaluate dose-sparing effects of medetomidine-midazolam (MM), acepromazine-butorphanol (AB), and midazolam-butorphanol (MB) on the induction dose of thiopental and propofol and to examine cardiopulmonary changes in dogs. ANIMALS: 23 healthy Beagles. PROCEDURE: Dogs were administered MM, AB, MB, or physiologic saline (0.9% NaCI) solution (PS) IM, and anesthesia was induced with thiopental or propofol. Cardiopulmonary measurements were obtained before and after administration of medication and 0, 5, 10, and 15 minutes after endotracheal intubation. RESULTS: Induction doses were reduced significantly by preanesthetic administration of MM, AB, and MB (thiopental, 20, 45, and 46% after administration of PS; propofol, 42, 58, and 74% after administration of PS, respectively). Recovery time in dogs administered MM-thiopental or MM-propofol and AB-propofol were significantly prolonged, compared with recovery time in dogs administered PS-thiopental or PS-propofol. Relatively large cardiovascular changes were induced by administration of MM, which were sustained even after the induction of anesthesia. Administration of AB and MB induced cardiovascular changes during and immediately after endotracheal intubation that were significantly decreased by induction with thiopental or propofol. However, mild hypotension developed with AB-propofol. Apnea was observed in dogs administered MM during induction of anesthesia, but most respiratory variables did not change significantly. CONCLUSIONS AND CLINICAL RELEVANCE: Preanesthetic medication with MM greatly reduced the anesthesia induction dose of thiopental and propofol but caused noticeable cardiopulmonary changes. Preanesthetic medication with AB and MB moderately reduced the induction dose of thiopental and propofol and amelio rated cardiovascular changes induced by these anesthetics, although AB caused mild hypotension.

Acepromazine↗