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Sufentanil and medetomidine anaesthesia in the rat and its reversal with atipamezole and butorphanol.

Injectable anaesthetics are widely used to anaesthetize rats, but recovery times are often prolonged. Reversible anaesthetic regimens have the advantage that animals may be recovered quickly, thus reducing the incidence of postoperative complications such as hypothermia, and also providing a means of treating inadvertent anaesthetic overdose. This study assessed and compared the characteristics of anaesthesia induced with combinations of sufentanil and medetomidine administered as a single subcutaneous or intraperitoneal dose, and reversal with butorphanol and atipamezole. Combinations of sufentanil/medetomidine at 40 microg/150 microg and 50 microg/150 microg/kg administered subcutaneously, and 80 microg/300 microg/kg by intraperitoneal injection were found to produce surgical anaesthesia for 101+/-49, 124+/-45 and 76+/-23 min (means +/- SD) respectively. All three combinations produced marked respiratory depression 30 min after injection (< 50% of resting respiratory rate). Oxygen saturation, measured by pulse oximetry, was < 50% in all groups 30 min following drug administration. Subcutaneous administration is recommended since it resulted in a more reliable and more rapid induction of anaesthesia than intraperitoneal administration. The administration of butorphanol and atipamezole (0.2/0.5 mg/kg s.c.) resulted in a rapid (< 7 min) reversal of anaesthesia and an associated respiratory depression. The induction of anaesthesia with sufentanil/medetomidine and its reversal with a combination of atipamezole and butorphanol is an effective technique for anaesthetizing rats. However, due to the marked respiratory depression and the resulting hypoxia, we recommend that this regimen should only be used in animals which are free from respiratory disease and that oxygen should be provided during anaesthesia.

Anesthesia↗

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.

Animals↗

Cardiopulmonary effects of a combination of medetomidine and butorphanol in atropinized pigs.

Cardiopulmonary effects of a combination of medetomidine and butorphanol were evaluated in atropinized pigs. This combination unchanged the cardiac output and significantly lowered the oxygen consumption compared with base-line values. Although some statistically significant changes were recorded, both medetomidine and butorphanol did not have a marked effect on the cardiopulmonary parameters in atropinized pigs. It was indicated that the administration of the combination of medetomidine and butorphanol is relatively safe in atropinized pigs.

Adrenergic alpha-Agonists↗

Medetomidine-ketamine-butorphanol anesthetic combinations in binturongs (Arctictis binturong).

The efficacy, safety, and reliability of two ketamine-medetomidine-butorphanol anesthetic combinations were evaluated in 34 adult binturongs (Arctictis binturong). The animals were randomly assigned to one of the two groups. On the basis of estimated body weights, group high ketamine (HK) received ketamine (8 mg/kg, i.m.), medetomidine (0.02 mg/kg, i.m.), and butorphanol (0.2 mg/kg, i.m.) combined in a single injection, and group low ketamine (LK) received ketamine (2 mg/kg, i.m.), medetomidine (0.04 mg/kg, i.m.), and butorphanol (0.2 mg/kg, i.m.). Cardiopulmonary parameters were measured for approximately 45 min; the animals were then administered atipamezole (5 mg/mg medetomidine, i.m.). Individual responses varied greatly to the anesthetic combinations, but similar numbers of animals in each group needed supplemental anesthetic agents (seven in group HK and six in group LK). Mean heart rates were higher in the LK group throughout anesthesia. Animals in both groups were mildly to moderately hypoxemic, but oxygenation improved in both groups following supplemental oxygen administration. Respiratory rates, arterial blood pressures, body temperatures, and end-tidal CO2 values were similar in both groups. Both protocols were effective; however, the LK combination is preferable because the mean recovery time was shorter.

Anesthetics, Combined↗

Butorphanol and azaperone as a safe alternative for repeated chemical restraint in captive white rhinoceros (Ceratotherium simum).

Anesthesia in the white rhinoceros (Ceratotherium simum) has routinely involved potent narcotic anesthetic agents such as etorphine or carfentanil with their associated adverse side effects. In captive rhinoceroses conditioned to routine handling, a combination of butorphanol and azaperone at mean (+/- SD) doses of 69.3 +/- 18.0 mg and 103.1 +/- 20.9 mg, respectively, was used to produce levels of neuroleptanalgesia ranging from light "standing" sedation to deeper planes of anesthesia producing sternal and lateral recumbency. This combination was used for repeated (minimum repeat frequency of 3 days between events) anesthetic episodes (n = 26) in two animals, with the remaining episode performed in a white rhinoceros with chronic renal disease. The action of butorphanol was satisfactorily reversed with naltrexone (125 mg i.v. and 125 mg i.m.). Results (mean +/- SD) include sternal recumbency achieved in 14.1 +/- 8.1 min after i.m. dosing, standing and ambulation occurred in 1.7 +/- 0.6 min after reversal, heart rate was 62.0 +/- 10.1 beats/min, respiratory rate was 14.7 +/- 5.6 breaths/min, and percentage of oxygen saturation of hemoglobin (Spo2) was 89.2 +/- 3.0%. Without supplementation, the total elapsed time ranged from 44.9 min to 103.0 min, whereas elapsed times up to 214.3 min were achieved with supplementation (mean time to supplementation was 28.0 +/- 13.9 min after initial dosing). Butorphanol and azaperone produced adequate muscle relaxation and apparently adequate analgesia for minor surgical interferences, including abdominal laparoscopy. Respiratory rates and Spo2 measurements were improved compared with reports of using more potent opioids in this species.

Analgesics, Opioid↗

Effects of continuous rate intravenous infusion of butorphanol on physiologic and outcome variables in horses after celiotomy.

A randomized, controlled, blinded clinical trial was performed to determine whether butorphanol administered by continuous rate infusion (CRI) for 24 hours after abdominal surgery would decrease pain and surgical stress responses and improve recovery in horses. Thirty-one horses undergoing exploratory celiotomy for abdominal pain were randomly assigned to receive butorphanol CRI (13 microg/kg/h for 24 hours after surgery; treatment) or isotonic saline (control). All horses received flunixin meglumine (1.1 mg/kg IV q12h). There were no significant differences between treatment and control horses in preoperative or operative variables. Treatment horses had significantly lower plasma cortisol concentration compared with control horses at 2, 8, 12, 24, 36, and 48 hours after surgery. Mean weight loss while hospitalized was significantly less for treatment horses than control horses, whether expressed as total decrease in body weight (13.9+/-3.4 and 27.9+/-4.5 kg, respectively) or as a percentage decrease in body weight (2.6+/-0.7 and 6.3+/-1.1%, respectively). Treatment horses were significantly delayed in time to first passage of feces (median times of 15 and 4 hours, respectively). Treatment horses had significantly improved behavior scores during the first 24 hours after surgery, consistent with the conclusion that they experienced less pain during that time. Butorphanol CRI during the immediate postoperative period significantly decreased plasma cortisol concentrations and improved recovery characteristics in horses undergoing abdominal surgery.

Analgesics, Opioid↗

Evaluation of the analgesic effects of epidurally administered morphine, alfentanil, butorphanol, tramadol, and U50488H in horses.

OBJECTIVE: To evaluate and compare effects of epidurally administered morphine, alfentanil, butorphanol, tramadol, and U50488H on avoidance threshold to noxious electrical stimulation over the dermatomes of the perineal, sacral, lumbar, and thoracic regions in horses. ANIMALS: 5 healthy adult horses. PROCEDURE: Using a Latin square complete repeated-measures design, horses were randomly assigned to receive 1 of 6 treatments (morphine, alfentanil, butorphanol, tramadol, U50488H, or sterile water) at intervals of at least 7 days. Agents were injected epidurally at the first intercoccygeal epidural space, and electrical stimulation was applied at repeated intervals for 24 hours to the dermatomes of the perineal, sacral, lumbar, and thoracic regions. Avoidance threshold to electrical stimulation was recorded. RESULTS: Administration of butorphanol, U50488H, and sterile water did not induce change in avoidance threshold. Alfentanil increased avoidance threshold during the first 4 hours, but not significantly. Tramadol and morphine significantly increased threshold and analgesic effects. Complete analgesia (avoidance threshold, >40 V) in the perineal and sacral areas was achieved 30 minutes after tramadol injection, compared with 6 hours after morphine injection. Duration of complete analgesia was 4 hours and 5 hours after tramadol and morphine injections, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Epidural administration of tramadol and morphine induces long-lasting analgesia in healthy adult horses. Epidural administration of opioids may provide long-lasting analgesia in horses without excitation of the CNS.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Use of thermal threshold response to evaluate the antinociceptive effects of butorphanol in cats.

OBJECTIVE: To characterize the antinociceptive actions of several doses of butorphanol by use of a thermal threshold testing device specifically designed for cats. ANIMALS: 6 domestic shorthair cats. PROCEDURE: The study was a masked, randomized, crossover design. Thermal thresholds were measured by use of a thermal threshold-testing device specifically developed for cats. A small probe containing a heater element and temperature sensor was held with consistent contact against a shaved area of the cat's skin with an elasticized band. Skin temperature was recorded before each test, prior to activation of the heater. On detection of a response (eg, the cat flinched, turned, or jumped), the stimulus was terminated and the threshold temperature recorded. Three baseline measurements were recorded before IV injection of 0.1, 0.2, 0.4, or 0.8 mg of butorphanol/kg. Each cat received all doses in a randomized order at least 1 week apart. The investigator was unaware of the treatment received. Thermal thresholds were measured every 15 minutes for 6 hours. RESULTS: Mean+/-SD pretreatment threshold temperature for all cats was 40.8+/-2.2 degrees C. There were no dose-related differences among treatments. There was a significant increase in threshold values for all treatments from 15 to 90 minutes after injection. Mydriasis was detected in all cats after treatment with butorphanol and dysphoric behavior was frequently exhibited. CONCLUSIONS AND CLINICAL RELEVANCE: Results obtained by use of a thermal stimulus indicated that the duration of antinociceptive action of butorphanol was 90 minutes and there was no dose-response relationship in cats.

Analgesics↗

Butorphanol tartrate acts to decrease sow activity, which could lead to reduced pig crushing.

The objective of this study was to determine whether administration of an analgesic to sows immediately after farrowing would allow them to lie more restfully. Sows lying on their pigs, causing them to be "crushed," is a major cause of pig mortality. Most deaths due to crushing occur during the first 3 d postpartum. For modern, lean-type sows, farrowing crates are relatively hard and unforgiving, even though they may be equipped with plastic-coated, expanded metal flooring. Indeed, many sows develop pressure sores on their shoulders, and this may contribute to the sows' discomfort. These sores may cause a sow to change position frequently to alleviate pain, thus increasing its chances of crushing pigs. Sixteen production sows were assigned to either a control group (C, n = 8) with litter size 11.71+/-.78 or an experimental group (B, n = 8) with litter size 11.63+/-1.22. Pigs born to C and B sows weighed 1.60+/-.04 and 1.37+/-.04 kg, respectively. The C sows were given no treatment, whereas the B sows were administered an i.m. injection of butorphanol tartrate at a dose of .15 mg/kg BW every 6 h until 3 d after farrowing. Data were collected on all sows using time-lapse photography (1 frame/.4 s) for a 3-d duration upon the initiation of farrowing. To assess the degree of comfort of each sow, body position changes were recorded when sows switched between lying, sitting, and standing. Data were analyzed by 12-h periods using Wilcoxon-Mann-Whitney equations. During the 72-h period, B sows tended to perform fewer position changes than C sows (P = .10). Specifically, position changes were fewer for B sows from 48 to 72 h postpartum (P<.06). There were no differences in position changes between treatments from 0 to 48 h postpartum (P>.50). There was no difference in the rate of crushing between treatments (C = 5, B = 5). The butorphanol did not seem to affect pig activity or normal behaviors or to create adverse effects, such as diarrhea. Although the sows given butorphanol showed a reduced number of position changes, the dose was intermediate, and a higher dose may have a greater effect. If pig mortality can be decreased, an analgesic protocol that is simple to administer and readily available to producers can be developed. Alternatively, using of more pliable flooring or an increase in sow body fat may allow sows to lie more stationary.

Analgesics, Opioid↗

Efficacy and safety of preoperative etodolac and butorphanol administration in dogs undergoing ovariohysterectomy.

Eighteen dogs undergoing ovariohysterectomy were premedicated with etodolac, butorphanol, or their combination. Various parameters, such as blood pressure, isoflurane requirements, behavioral pain scores, plasma cortisol concentration, plasma glucose concentration, and mucosal bleeding time, were assessed. The integrated plasma cortisol values were significantly lower in the etodolac and etodolac with butorphanol groups. Dogs receiving etodolac and butorphanol had the lowest behavioral pain scores from extubation until the end of monitoring. Isoflurane concentration over time (area under the curve), buccal mucosal bleeding time, and indices of renal function were not significantly different among the treatment groups.

Animals↗

A comparison of haemodynamic response with pethidine vs. butorphanol in open cholecystectomy cases.

OBJECTIVE: The present study was undertaken to compare the haemodynamic responses with pethidine vs. Butorphanol intraoperatively in open cholecystectomy cases in KMCTH. METHOD: In this randomized study, all together 40 patients undergoing routine cholecystectomy surgery were included. Group A received Pethidine 1 mg/kg and Group B received Butorphanol 0.04 mg/kg intraoperatively. Heart rate and blood pressure were recorded before injection of the drug, after injection, before intubation, after intubation, before skin incision, after incision, before extubation and after extubation data analysis was done using independent sample t test. RESULT: Our study showed no statistical significance in haemodynamic responses with either pethidine or Butorphanol in open cholecystectomy cases. CONCLUSION: Both drugs appear equally good analgesics in our study.

Adjuvants, Anesthesia↗

Epidural butorphanol augments lidocaine sensory anesthesia during labor.

To determine the efficacy and safety of epidural butorphanol combined with lidocaine, 50 healthy parturients were studied during labor and delivery. All patients received a test dose of 3 ml 1.5% lidocaine with 1:200,000 epinephrine. Patients were then randomly assigned to receive 7 ml of one of two epidural regimens in a double-blind fashion: Group 1 patients received 1.5% lidocaine plus 1 mg butorphanol plus 1:300,000 epinephrine; Group 2 patients received 1.5% lidocaine plus 1:300,000 epinephrine. Each group consisted of 25 patients. The study ended at the time of redosing. All subsequent epidural injections were made with one bolus of plain 0.25% bupivacaine followed by continuous infusion of 0.125% bupivacaine. Duration of anesthesia was significantly longer for Group 1 compared to Group 2 (p less than 0.01), 124 +/- 8 minutes versus 99 +/- 6 minutes (mean +/- SEM). There were no difference between groups in duration of first and second stages of labor, method of delivery or neonatal outcome. Umbilical cord acid-base status and neurologic adaptive capacity scores did not differ significantly between the two groups. The authors conclude that adding small doses of butorphanol to epidural lidocaine during labor is effective and safe.

Adult↗

Butorphanol in perspective.

Butorphanol tartrate is a highly effective opioid agonist-antagonist analgesic with qualitative as well as quantitative differences from the pure agonists. These differences are thought to be due to interaction with a distinct subset of opioid receptors. Although it relieves severe pain, the drug does not usually elevate mood, and it may occasionally cause dysphoria. Counterbalancing its disadvantages is a wealth of clinical experience with the drug showing an impressive record of safety. Butorphanol produces limited respiratory depression and smooth muscle spasm, and both effects are reversible with naloxone. The most prominent side effect is sedation, a property that is generally quite useful in the perioperative period. Butorphanol is a weak morphine antagonist, so it may interact with agonists like morphine or fentanyl. The chief advantages of this agent are its low toxicity and very low potential for abuse.

Animals↗

Butorphanol improves CO2 response and ventilation after fentanyl anesthesia.

We have determined that the mixed agonist-antagonist narcotic, butorphanol, improves CO2 response and ventilation after fentanyl anesthesia. A tentative dosage range has been established. Twenty-two patients were anesthetized with isoflurane, nitrous oxide, and fentanyl, which was continuously infused throughout the study. Postoperatively three 1-mg doses of butorphanol were administered IV. Blood pressure, heart rate, plasma epinephrine and norepinephrine concentrations, and pain intensity were essentially unchanged after butorphanol. Most of the improvement in breathing occurred after the first 1-mg dose. Mean respiratory rate increased from 7.8 +/- 5.0 to 11.0 +/- 4.8 min-1 (P less than or equal to 0.005), tidal volume increased from 469 +/- 302 to 844 +/- 390 ml (P less than or equal to 0.005), minute ventilation increased from 4.32 +/- 2.97 to 8.51 +/- 3.14 L/min (P less than or equal to 0.005), and the slope of the ventilatory response to CO2 increased from 0.36 +/- 0.37 to 0.90 +/- 0.80 L X min-1 X mm Hg-1 (P less than or equal to 0.05). Resting PaCO2 decreased from a baseline of 57.8 +/- 11.1 to 51.7 +/- 5.12 mm Hg (P less than or equal to 0.05) after the third dose.

Anesthesia Recovery Period↗

Effects of metoclopramide, clenbuterol and butorphanol on ruminoreticular motility of calves.

Rate and amplitude of contractions of the rumen dorsal sac and reticulum of 6 male Holstein calves ages 12 to 20 weeks were monitored with electromyography, strain gauges and an intraruminal pressure catheter. Heart rate and mean arterial pressure were measured with ultrasound. The effects of metoclopramide, a dopamine antagonist, clenbuterol, a beta-2 adrenergic agonist, and butorphanol, a narcotic agonist/antagonist, were observed utilizing dosages bracketing those employed clinically. Metoclopramide significantly decreased the intraruminal pressure peaks associated with cyclical contractions without changing their rate. Clenbuterol had no measurable effect on the ruminoreticulum. Butorphanol totally inhibited ruminoreticular contractions for periods of 6 to greater than 40 min depending on dosage. Only clenbuterol significantly affected cardiovascular function; it increased heart rate and decreased mean arterial pressure. Both metoclopramide and butorphanol produced behavioral changes in the calves.

Animals↗

Patient-controlled analgesia using butorphanol for postoperative pain relief: an open-label study.

Patient-controlled analgesia (PCA) has been studied extensively for the treatment of postoperative pain using narcotic analgesics. Butorphanol, a nonnarcotic injectable analgesic, has not previously been investigated using this drug delivery mechanism. Twenty-five patients undergoing general abdominal surgery and general anesthesia used a PCA device with butorphanol as the analgesic agent. Most patients (84%) were able to obtain excellent postoperative pain relief. The role of butorphanol in the management of postoperative pain should be expanded to include patient-controlled drug delivery.

Adult↗

Double-blind comparison of butorphanol and morphine in patient-controlled analgesia.

In this study, the patient-controlled analgesia (PCA) technique was used to compare the suitability of butorphanol with that of morphine in relieving postoperative pain. Twelve patients, 19-77 years old, who had abdominal surgery, used the PCA device through the first 24-hour postoperative period. Results showed that all patients expressed satisfaction with the PCA technique. Analysis of the degree of discomfort according to the verbal description scale, recordings of respiratory rate, and assessment of sedation status showed no significant differences between patients who received butorphanol and those who received morphine. Patients were able to maintain acceptable analgesia with minimal sedation. There were no adverse side effects reported with butorphanol.

Adult↗

Outpatient sedation for oral surgery: a comparison of butorphanol and fentanyl.

Third molar surgery in the oral and maxillofacial surgery office has been a predictable model for evaluating the efficacy of sedatives and analgesics. In this setting, butorphanol plus diazepam and fentanyl plus diazepam were compared for surgical effectiveness and postoperative recovery. The comparison of butorphanol to a known sedative combination was clinically very satisfactory. It appears from this data that butorphanol has a pharmacologic place in outpatient conscious sedation.

Adult↗