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Anaesthetic and cardiopulmonary effects of balanced anaesthesia with medetomidine-midazolam and butorphanol in dogs.

The anaesthetic and cardiopulmonary effects of combinations of medetomidine (Me), midazolam (Mi) and butorphanol (Bu) were evaluated in dogs. The characterization of anaesthetic effects was assessed using a scoring system. The combinations tested were 20 or 40 micrograms/kg Me and 0.5 mg/kg Mi (20Me-Mi or 40Me-Mi) followed by either an intravenous injection of physiological saline solution (PSS) or Bu (0.1 or 0.3 mg/kg). The mixture of Me and Mi was injected intramuscularly, followed 15 min later by an intravenous injection of Bu or PSS in all six groups. The combined Me-Mi induced deep sedation but not profound anaesthesia. The effect of the subsequent Bu administration was observed in the scores related to its analgesic effect. There were no significant differences between the two doses of Bu, following either 20Me-Mi or 40Me-Mi in the duration of anaesthesia, heart and respiratory rates, rectal temperature, and anaesthetic and analgesic scores except for palpebral reflex, and interdigital web clamping scores. Therefore, we concluded that the addition of 0.1 mg/kg Bu to Me-Mi elicits adequate anaesthesia with adequate analgesic effect, and side-effects such as bradycardia, hypertension, and slight respiratory acidosis in some dogs.

Adrenergic alpha-Agonists↗

Quantitative electroencephalography of medetomidine, medetomidine-midazolam and medetomidine-midazolam-butorphanol in dogs.

The purpose of this study was to evaluate the effects of the administration of an alpha2-adrenoceptor agonist alone and in combination with other derivatives on brain wave activity. In addition, the diagnostic values of the electroencephalogram (EEG) for judging the depth of the balanced anaesthesia with an alpha2-adrenoceptor agonist was evaluated. The treatments comprised 20 microg/kg medetomidine (Me-20), 80 microg/kg medetomidine (Me-80), 20 microg/kg medetomidine and 0.5 mg/kg midazolam (Me-Mi) administered intramuscularly, and 20 microg/kg medetomidine with 0.5 mg/kg midazolam and 0.1 mg/kg butorphanol (Me-Mi-Bu). The EEG was recorded continuously at pre-administration, and at 7, 10, 20, 30, 45 and 60 min after administration. The recorded data were analysed by separating the power spectrum into 1-3, 4-7, 8-13 and 14-30 Hz bands. Spectral-edge analysis was used to calculate the spectral edge frequency 90 (SEF90) and the median edge frequency (MEF). Time-related changes in power spectrum analysis showed a significant increase in the Me-80 group in the 1-3 Hz band. The power for 1-3 Hz in the Me-80 group was significantly higher than in all the other groups. In the 14-30 Hz band, there was a significant reduction of power in all groups following administration of the agents. The SEF90 frequencies were significantly reduced in all groups except for the Me-20 group after administration of the agents. The SEF90 frequencies in the Me-20, Me-Mi and Me-Mi-Bu were all significantly higher than those in the Me-80 group. However, there was no significant difference between the Me-20, Me-Mi and Me-Mi-Bu groups in any analyses. Our results demonstrated that the changes in quantitative EEG made by the Me-Mi-Bu and Me-Mi groups were similar to those made by Me-20 groups. Present results suggest that the EEG should be interpreted with caution in assessing the anaesthetic level in balanced anaesthesia in dogs.

Adrenergic alpha-Agonists↗

Chemical restraint of peccaries with tiletamine/zolazepam and xylazine or tiletamine/zolazepam and butorphanol.

OBJECTIVE: To evaluate the use of a combination of tiletamine/zolazepam and xylazine (TZX) in collared and white-lipped peccaries and to compare its efficacy as an anesthetic technique with that of tiletamine/zolazepam and butorphanol (TZB). STUDY DESIGN: Prospective experimental trial. ANIMALS: Seven white-lipped peccaries (Tayassu pecari) (four females and three males) and four collared peccaries (Tayasu tajacu) (two males and two females). METHODS: Animal immobilization was attempted with TZX and TZB (IM) on two different occasions. Heart and respiratory rates (HR, RR), rectal temperature (RT), sedation, muscle relaxation, posture, auditory response and analgesia were evaluated every 15 minutes during immobilization. Induction, anesthesia, standing and walking time were determined after drug administration. RESULTS: Doses for white-lipped peccaries were 1.23 +/- 0.26 mg kg(-1) (mean +/- SD) of TZ and 1.23 +/- 0.26 mg kg(-1) of X, and 1.46 +/- 0.09 mg kg(-1) of TZ and 0.14 +/- 0.008 mg kg(-1) of B; doses for collared peccaries were 1.51 +/- 0.29 mg kg(-1) of TZ and 1.51 +/- 0.29 mg kg(-1) of X and 1.68 +/- 0.02 mg kg(-1) of TZ and 0.17 +/- 0.002 mg kg(-1) of B. In white-lipped peccaries, both drug combinations provided a smooth induction and good immobilization for more than an hour. Anesthesia and standing times were significantly longer in animals given TZB, whereas walking time was significantly longer in animals given TZX. A significant decrease in HR was observed with both treatments. Respiratory rate decreased significantly with TZX, but the rate remained higher than with TZB. Induction and recovery quality in white-lipped peccaries was better with TZB than with TZX. Neither protocol provided adequate immobilization in collared peccaries. CONCLUSION AND CLINICAL RELEVANCE: At the doses described, TZB is effective in providing a long period of immobilization, whereas TZX is adequate for short to medium immobilization in white-lipped peccaries. Neither drug combination was effective in collared peccaries at the doses given.

Adrenergic alpha-Agonists↗

Effectiveness of Stadol NS (butorphanol tartrate) with ibuprofen in the treatment of pain after laser-assisted uvulopalatopharyngoplasty.

PURPOSE: Laser-assisted uvulopalatopharyngoplasty (LA-UPPP) is a recently developed technique for treating snoring and mild sleep apnea. This treatment is associated with severe postoperative pain. This study evaluated the effectiveness and safety of transnasal administration of butorphanol tartrate (Stadol NS; Bristol-Myers Squibb, New York, NY) as a primary means of controlling pain after this surgical procedure. PATIENTS AND METHODS: Twenty patients (14 men and 6 women; mean age, 43 years) were enrolled and treated with LA-UPPP and radiofrequency turbinate procedures (coblation) for severe snoring and chronic nasal congestion in an open label study. The same surgeon performed all procedures. Patients were advised to take 2 tablets of ibuprofen (200 mg each) and use a single 1 mg spray of Stadol NS in 1 nostril for the initial dose. If adequate pain relief was not achieved in 1 to 1.5 hours, an additional 1 mg dose of Stadol NS was recommended. Thereafter, they could repeat the ibuprofen and Stadol NS every 3 to 4 hours, as needed. Comprehensive preoperative and postoperative evaluations were made using a visual analog scale of 0 to 10, with 0 equal to no pain and 10 being the most severe. Patients were followed-up for 14 days. RESULTS: All 20 patients had LA-UPPP and nasal turbinate radiofrequency coblation, and all 20 were eligible for both efficacy and safety analysis. Pain was reduced from a mean of 6.6 to a mean of 3.3 (50%) after an average of 48 minutes after the initial dose. CONCLUSION: Stadol NS appears to be an effective treatment for moderate-to-severe pain after LA-UPPP. If patients have difficulty swallowing, which is the case with most throat surgeries performed by oral and maxillofacial surgeons and otolaryngologists, the transnasal route of administration reduces the number of oral medications taken by the patient.

Administration, Inhalation↗

Postoperative pain control in cats: clinical trials with medetomidine and butorphanol.

OBJECTIVE: To evaluate the analgesic effects of medetomidine (MED) and butorphanol (BTO) in cats after ovariohysterectomy. STUDY DESIGN: A placebo-controlled, blinded monocenter clinical study. ANIMALS: Healthy adult female client-owned cats. METHODS: Sixty-four cats weighing 3.15 +/- 0.6 kg, presented to the University of Helsinki's Small Animal Teaching Hospital for routine elective ovariohysterectomy, received MED at 15 microg/kg (n = 18), BTO at 0.1 mg/kg (n = 23), or saline (PL) (n = 23) intramuscularly immediately after ovariohysterectomy. Level of pain perception, degree of restlessness, and extent of sedation were scored subjectively before and at 30, 60, 90, and 120 minutes after test-drug administration. RESULTS: BTO provided the best pain relief, followed by MED. Saline provided the least pain relief. Both MED and BTO effectively and identically prevented postoperative restlessness. MED and BTO produced an identical degree of sedation that was better than the PL. CONCLUSIONS: Both MED (at 15 microg/kg) and BTO (at 0.1 mg/kg) prevent postoperative pain in cats after ovariohysterectomy. Clinical Relevance-MED and BTO are useful for preventing postoperative pain in cats.

Analgesics, Non-Narcotic↗

Effect of butorphanol tartrate on food and water consumption in humans.

There is much evidence that endogenous opioid peptides are involved in the regulation of food and water intake in a variety of species. We report here that the exogenous opiate agonist, butorphanol tartrate (1 microgram/kg), significantly increases food, but not water, intake in normal humans. The major effect on food intake was seen within the first 2 h after the administration of drug. These findings suggest that this drug may be therapeutically useful in patients with cancer anorexia.

Adult↗

The use and assessment of ketamine-medetomidine-butorphanol combinations for field anaesthesia in wild European badgers (Meles meles).

OBJECTIVE: To evaluate the effectiveness of four ketamine-based anaesthetics in badgers using a quantitative anaesthesia assessment technique. STUDY DESIGN: Prospective randomized 'blinded' experimental trial. METHODS: The quality of induction, of anaesthesia (at 5-minute intervals) and of recovery were assessed in 93 badgers, given either one of three ketamine (K)-medetomidine (M)-butorphanol (B) combinations: group A - M K B at 20/40/80 microg kg(-1); group B - M K B at 20/40/60 microg kg(-1); and group C - M K B at 20/60/40 microg kg(-1), or ketamine (K) alone at 2 mg kg(-1) (group D). The assessor was ignorant of the combination administered. Physiological variables (heart and respiratory rates and rectal temperature) were measured at 5-minute intervals during anaesthesia. Gingival mucus membrane colour was also recorded. RESULTS: Induction to anaesthesia was most rapid with ketamine (2 mg kg(-1)) although induction quality did not differ between techniques. Ketamine used alone gave the poorest score for anaesthesia quality. Heart rate (HR) and scores for gingival mucus membrane colour were higher in animals anaesthetized with ketamine alone. Rectal temperature did not differ significantly between the techniques at any time during anaesthesia. Ketamine used alone produced the poorest quality of recovery. CONCLUSION AND CLINICAL RELEVANCE: The M-K-B combinations investigated overcame several side effects associated with ketamine anaesthesia, but at the expense of more variable induction times, lower HRs, and poorer mucus membrane coloration.

Anesthesia↗

Detomidine-butorphanol sedation in equine clinical practice.

Combinations of detomidine (mean dose rate 13 micrograms/kg) and butorphanol (mean dose rate 26 micrograms/kg) were used to sedate 61 horses for a variety of surgical or diagnostic procedures in general equine practice. Three horses were sedated on more than one occasion. The degree of sedation was graded from 3 to 0 (deep sedation to no effect) and any side effects were recorded. Forty-three per cent of the horses were graded 3, 46 per cent were graded 2, 8 per cent were graded 1 and 3 per cent were graded 0. Bradycardia and ataxia were the major side effects. The combination was judged to be effective and safe for use in general practice. In 56 horses (92 per cent) the necessary procedure was carried out under excellent conditions and in only one horse was the degree of sedation considered to be totally unsatisfactory.

Animals↗

An open evaluation of oral butorphanol as long-term therapy in out-patients suffering from moderate to severe chronic pain.

This open study evaluated the safety, tolerance and efficacy of multiple oral doses of butorphanol tartrate as long-term therapy for moderate to severe pain of various aetiologies. Twenty patients were given doses ranging from four to twelve 4 mg tablets per day for a period of 3 to 201 days (median 87 days). Median pain relief over the entire study was rated as good, very good or excellent in eleven patients (55%) and poor to fair in the remaining nine patients (45%). Global assessments were as follows: good to very good--twelve patients; poor to fair--eight patients. Ten of the twenty patients treated reported side-effects (sedation, light-headedness, dizziness, insomnia and headache) ranging from mild to severe. No drug-related abnormalities with respect to blood pressure, body-weight or laboratory data were evident.

Administration, Oral↗

Oral butorphanol tartrate for the long-term treatment of out-patients with moderate to severe cancer pain.

The safety, tolerance and analgesic efficacy of multiple oral doses of butorphanol tartrate for the long-term treatment of cancer pain were evaluated in this open study. Thirty-five patients were treated with various doses (1 to 12 tablets per day) for 4 to 147 days. The median pain relief was fair, good, very good or excellent in 51% of the patients and poor in 49% of the patients. Global assessments were very similar. No clinically significant changes in blood pressure, weight, blood and urine chemistries were observed. Seventeen patients reported side-effects (only sedation and dry mouth) ranging from mild to severe.

Adult↗

Fentanyl and medetomidine anaesthesia in the rat and its reversal using atipamazole and either nalbuphine or butorphanol.

The intraperitoneal injection of anaesthetic agents is a simple and convenient method of anaesthetizing rats. However, all of the anaesthetic combinations in current use which are administered by intraperitoneal injection produce prolonged sedation, and full recovery of consciousness may take several hours. Fentanyl, a mu agonist opioid, and medetomidine, an alpha 2-adrenoceptor agonist were mixed and administered as a single intraperitoneal injection. Combinations of 300 micrograms/300 micrograms/kg and 300 micrograms/200 micrograms/kg of fentanyl/medetomidine were shown to produce surgical anaesthesia in the rat. This anaesthetic regimen produced significant respiratory depression (P less than 0.01) and animals did not regain their righting reflex until 193 +/- 21 min (mean +/- 1 SD) after injection. Administration by intraperitoneal injection of atipamezole, a specific alpha 2-adrenoceptor antagonist (1 mg/kg) mixed with a mu antagonist/k agonist opioid (nalbuphine, 2 mg/kg or butorphanol 0.4 mg/kg), resulted in a rapid (less than 8 min) reversal of anaesthesia and the associated respiratory depression, and apparent full recovery of consciousness.

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.

Anesthetics, Combined↗

Cardiopulmonary and anesthetic effects of medetomidine-ketamine-butorphanol and antagonism with atipamezole in servals (Felis serval).

Seven (three male and four female) 4-7-yr old captive servals (Felis serval) weighing 13.7 +/- 2.3 kg were used to evaluate the cardiopulmonary and anesthetic effects of combined intramuscular injections of medetomidine (47.4 +/- 10.3 microg/kg), ketamine (1.0 +/- 0.2 mg/kg), and butorphanol (0.2 +/- 0.03 mg/kg). Inductions were smooth and rapid (11.7 +/- 4.3 min) and resulted in good muscle relaxation. Significant decreases in heart rate (85 +/- 12 beats/min) at 10 min after injection and respiratory rate (27 +/- 10 breaths/min) at 5 min after injection continued throughout the immobilization period. Rectal temperature and arterial blood pressure did not change significantly. The PaO2 decreased significantly, and PaCO2 increased significantly during immobilization but remained within clinically acceptable limits. Hypoxemia (PaO2 < 60 mm Hg) was not noted, and arterial blood oxygen saturation (SaO2) was greater than 90% at all times. Relative arterial oxygen saturation (SpO2) values, indicated by pulse oximetry, were lower than SaO2 values. All animals could be safely handled while sedated. Administration of atipamezole (236.8 +/- 51.2 microg/kg half i.v. and half s.c.), an alpha2 antagonist, resulted in rapid (4.1 +/- 3 min to standing) and smooth recoveries.

Adrenergic alpha-Antagonists↗

Physiological response of gray wolves to butorphanol-xylazine immobilization and antagonism by naloxone and yohimbine.

Captive gray wolves (Canis lupus) were immobilized (loss of consciousness) with 2.0 mg/kg xylazine hydrochloride (XYL) and 0.4 mg/kg butorphanol tartrate (BUT) administered intramuscularly. Induction time was 11.8 +/- 0.8 min (mean +/- SE). Immobilization resulted in bradycardia, respiratory depression, and normotension. Fifteen min after induction, six wolves were given either 0.05 mg/kg naloxone hydrochloride (NAL) and 0.125 or 0.250 mg/kg yohimbine hydrochloride (YOH), or an equal volume of saline (control) intravenously. Antagonism resulted in shortened recovery times compared to control animals (P less than 0.03); there was no difference in recovery times between the YOH doses (P greater than 0.05). Antagonism caused increases in heart rate (HR) and respiratory rate (RR), but no changes in MABP. Eight other wolves were similarly immobilized, but given only NAL. This resulted in partial antagonism with the animals appearing to be sedated with XYL only. Three wolves given only 0.4 mg/kg BUT assumed a state described as "apathetic sedation." Three other wolves sedated with only 2.0 mg/kg XYL showed a profound sedation characterized by recumbency, bradycardia and shallow, but regular, respiration. This study demonstrated that (1) BUT and XYL together, but not separately, can completely immobilize wolves, (2) this combination can be rapidly antagonized by NAL and YOH, and (3) there appeared to be no adverse cardiopulmonary reactions to any of the drugs used.

Animals↗

[The interaction of moradol (butorphanol tartrate) and flormidal (midazolam) in the patient's body].

Twenty five female patients (3 groups) operated on for cholelithiasis without premedication have been examined. In patients of group F an effective flormidal dose (EFD) causing an unconscious state upon intravenous injection by a measuring device has been determined. Due to an insufficient sedative effect of moradol it was impossible to determine an effective moradol dose (EMD). In group M+F right after intravenous administration of a standard moradol dose (SMD) flormidal infusion was begun, as in patients of group F. EFD after moradol injection (EFMD) was determined. Making proportions with known EFD, EFMD and SMD values, EMD was calculated. Upon intravenous administration of the calculated EMD by a measuring device the sedative effect was superficial in all the patients of group M and it was impossible to achieve an unconscious state. The interaction of moradol (butorphanol tartrate) and flormidal (midazolam) in the patients' body is of synergic nature.

Butorphanol↗

Yohimbine/flumazenil antagonism of hemodynamic alterations induced by a combination of midazolam, xylazine, and butorphanol in dogs.

Reversal of hemodynamic alterations induced by midazolam maleate (1.0 mg/kg of body weight), xylazine hydrochloride (0.44 mg/kg), and butorphanol tartrate (0.1 mg/kg) with yohimbine (0.1 mg/kg) and flumazenil (0.25 mg/kg) was evaluated in 5 dogs. The dogs were anesthetized with isoflurane for instrumentation. With return to consciousness, baseline values were recorded, and the midazolam/xylazine/butorphanol mixture with glycopyrrolate was administered IV. Hemodynamic data were recorded for 60 minutes, and then a reversal mixture of yohimbine and flumazenil was administered IV. All variables were measured 1 minute from beginning of the reversal injection. Mean arterial pressure, pulmonary arterial pressure, systemic vascular resistance, and right ventricular stroke work index increased significantly (P < 0.05) above baseline at 60 minutes. Cardiac index and central venous pressure significantly decreased below baseline at 60 minutes. After reversal, mean arterial pressure and central venous pressure significantly decreased from baseline, whereas cardiac index, pulmonary arterial pressure, and right ventricular stroke work index increased significantly above baseline. Heart rate, cardiac index, and right ventricular stroke work index increased significantly above the 60-minute value after reversal. Mean arterial pressure and systemic vascular resistance decreased significantly (P < 0.05) below the 60-minute value after reversal. The hemodynamic alterations accompanying midazolam/xylazine/butorphanol sedation-anesthesia may be rapidly reversed with a combination of yohimbine and flumazenil.

Anesthesia↗

Pharmacokinetics of butorphanol tartrate in rabbits.

The pharmacokinetic properties of butorphanol tartrate were determined in 7 rabbits after IV and SC injection (0.5 mg/kg of body weight). A 2-compartment model (biexponential) best represented the concentration vs time curve after IV injection. The half-life was calculated to be 1.64 hours via IV administration, whereas SC injection resulted in an elimination half-life of 3.16 hours.

Animals↗

Fibrous myopathy from butorphanol injections.

We describe an unusual, and probably underrecognized manifestation of intramuscular narcotic abuse. Fibrous myopathy is a deforming, fibrous infiltration of the muscles used for injection over a prolonged period. It is usually associated with pentazocine or meperidine injections, and to our knowledge, this is the first report of butorphanol causing the entity.

Adult↗