Contamination of multidose butorphanol vials in small animal general practices.

OBJECTIVES: To assess and quantify medetomidine contamination of butorphanol multidose vials in small animal general practices and determine if practice policies and procedures regarding drug handling, as determined by questionnaire, impact upon contamination level. METHODS: Samples of butorphanol were withdrawn from in-use vials in participating practices in June and July 2013. Samples were analysed using high-performance liquid chromatography and mass spectrometry. RESULTS: Forty-one samples were obtained from 31 practices. Contamination was detected in 29 samples from 10 mL vials. The mean (αsd) contamination was 0 · 275 (α0 · 393) µg/mL; maximum contamination in any vial was 2 · 034 µg/mL. There was no correlation between volume of the vial used and the level of contamination. None of the survey factors predicted contamination levels of the vials. CLINICAL SIGNIFICANCE: Contamination of butorphanol multidose vials with medetomidine was common but the level of contamination was insufficient to cause detrimental effects in dogs if butorphanol were to be administered alone. The potential for sporadic higher levels of contamination must be taken into account, especially when using 50 mL vials when sedating critically ill cases, because there is a risk of clinical side effects.

Compatibility of butorphanol and droperidol in 0.9% sodium chloride injection.

PURPOSE: The compatibility and stability of butorphanol tartrate and droperidol in polyvinyl chloride (PVC) bags and glass bottles stored at 4°C and 25°C for up to 15 days were studied. METHODS: Admixtures were assessed initially and for 15 days after preparation in PVC bags and glass bottles using 0.9% sodium chloride injection as a diluent and stored at 4°C and 25°C. The initial drug concentrations were 0.08 mg/mL for butorphanol tartrate and 0.05 mg/mL for droperidol. Samples were withdrawn from each container immediately after preparation and at predetermined intervals (2, 4, 8, 24, 48, 72, 120, 168, 240, and 360 hours after preparation). The solutions were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. Drug concentrations were determined using a validated high-pressure liquid chromatography method. RESULTS: After 15 days of storage, all formulations tested retained >98% of the initial concentrations of both drugs. The drug mixtures were clear in appearance, and no color change or precipitation was observed. Throughout this period, pH values remained stable. CONCLUSION: Admixtures of butorphanol tartrate 0.08 mg/mL and droperidol 0.05 mg/mL in 0.9% sodium chloride injection were stable for at least 360 hours when stored in PVC bags or glass bottles at 4°C and 25°C and protected from light.

Separation of enantiomers of butorphanol and cycloamine by capillary zone electrophoresis.

Butorphanol tartrate is a synthetic opioid agonist-antagonist used as analgesic, possessing three chiral centres in the basic part of the molecule. Its chiral purity is routinely controlled only by optical rotation. A new capillary zone electrophoresis method, capable to separate the enantiomers of butorphanol and intermediate of its synthesis, cycloamine, was developed. Different electrolyte composition (type and concentration of carrier ion, pH, and organic solvent addition), and type and concentration of several chiral selectors (natural and modified cyclodextrins) were tested. Using the optimized conditions (acidic electrolyte with the addition of highly sulphated gamma-cyclodextrin) as low as 0.05% of undesirable enantiomers can be detected. Selected method characteristics, i.e., linearity (0-50 mg/l), precision (2.5% at 20 mg/l), and accuracy (101 +/- 2% at 20 mg/l) were evaluated. The optimized method was applied for the analysis of real batches of butorphanol and cycloamine. It was found that butorphanol tartrate manufactured by IVAX Pharmaceuticals contains less than 0.05% of undesirable enantiomer.

Detomidine-butorphanol-propofol for carotid artery translocation and castration or ovariectomy in goats.

OBJECTIVE: To determine the safety and efficacy of propofol, after detomidine-butorphanol premedication, for induction and anesthetic maintenance for carotid artery translocation and castration or ovariectomy in goats. STUDY DESIGN: Case series. ANIMALS: Nine 4-month-old Spanish goats (17.1 +/- 2.6 kg) were used to evaluate propofol anesthesia for carotid artery translocation and castration or ovariectomy. METHODS: Goats were premedicated with detomidine (10 micrograms/kg intramuscularly [i.m.]) and butorphanol (0.1 mg/kg i.m.) and induced with an initial bolus of propofol (3 to 4 mg/kg intravenously [i.v.]). If necessary for intubation, additional propofol was given in 5-mg (i.v.) increments. Propofol infusion (0.3 mg/kg/min i.v.) was used to maintain anesthesia, and oxygen was insufflated (5 L/min). The infusion rate was adjusted to maintain an acceptable anesthetic plane as determined by movement, muscle relaxation, ocular signs, response to surgery, and cardiopulmonary responses. Systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures, heart rate (HR), ECG, respiratory rate (RR), SpO2, and rectal temperature (T) were recorded every 5 minutes postinduction; arterial blood gas samples were collected every 15 minutes. Normally distributed data are represented as mean +/- SD; other data are medians (range). RESULTS: Propofol (4.3 +/- 0.9 mg/kg/min i.v.) produced smooth, rapid (15.2 +/- 6 sec) sternal recumbency. Propofol infusion (0.52 +/- 0.11 mg/kg/min i.v.) maintained anesthesia. Mean anesthesia time was 83 +/- 15 minutes. Muscle relaxation was good; eye signs indicated surgical anesthesia; two goats moved before surgery began; one goat moved twice during laparotomy. Means are reported over the course of the data collection period. Means during the anesthesia for pHa (arterial PH), PaCO2, PaO2, HCO3-, and BE (base excess) ranged from 7.233 +/- 0.067 to 7.319 +/- 0.026, 54.1 +/- 4.6 to 65.3 +/- 12.0 mm Hg, 133.1 +/- 45.4 to 183.8 +/- 75.1 mm Hg, 26.9 +/- 2.6 to 28.2 +/- 2.1 mEq/L, and -0.8 +/- 2.9 to 1.4 +/- 2.2 mEq/L. Means over time for MAP were 53 +/- 12 to 85 +/- 21 mm Hg. Mean HR varied over time from 81 +/- 6 to 91 +/- 11 beats/minute; mean RR, from 9 +/- 8 to 15 +/- 5 breaths/minute; SpO2 from 97 +/- 3% to 98 +/- 3%; mean T, from 36.0 +/- 0.6 degrees C to 39.1 +/- 0.7 degrees C. Over time, SpO2 and SaO2 did not change significantly; HR, RR, T, and PaCO2 decreased significantly; SAP, DAP, MAP, pHa, PaO2, and BE increased significantly. HCO3- concentrations increased significantly, peaking at 45 minutes. Recoveries were smooth and rapid; the time from the end of propofol infusion to extubation was 7.3 +/- 3 minutes, to sternal was 9.2 +/- 5 minutes, and to standing was 17.7 +/- 4 minutes. Median number of attempts to stand was two (range of one to four). Postoperative pain was mild to moderate. CONCLUSIONS: Detomidine-butorphanol-propofol provided good anesthesia for carotid artery translocation and neutering in goats. CLINICAL RELEVANCE: Detomidine-butorphanol-propofol anesthesia with oxygen insufflation may be safely used for surgical intervention in healthy goats.

A comparison of ketorolac with flunixin, butorphanol, and oxymorphone in controlling postoperative pain in dogs.

Ketorolac tromethamine, a nonsteroidal anti-inflammatory analgesic, was compared with flunixin and butorphanol for its analgesic efficacy and potential side effects after laparotomy or shoulder arthrotomy in dogs. Sixty-four dogs were randomly assigned to receive butorphanol 0.4 mg/kg body weight (BW) (n = 21), flunixin 1.0 mg/kg BW (n = 21), or ketorolac 0.5 mg/kg BW (n = 22), in a double blind fashion. The analgesic efficacy was rated from 1 to 4 (1 = inadequate, 4 = excellent) for each dog. The average scores after laparotomy were ketorolac, 3.4; flunixin, 2.7; and butorphanol, 1.6. After shoulder arthrotomy, the average scores were ketorolac, 3.5; flunixin, 3.0; and butorphanol, 1.4 (5/11 dogs). As butorphanol was unable to control pain after shoulder arthrotomy, oxymorphone, 0.05 mg/kg BW, replaced butorphanol in a subsequent group of dogs and had a score of 2.0 (6/11 dogs). Serum alanine aminotransferase and creatinine were significantly elevated above baseline at 24 hours postoperatively in dogs receiving flunixin. One dog in each group developed melena or hematochezia. One dog receiving ketorolac had histological evidence of gastric ulceration. We concluded that ketorolac is a good analgesic for postoperative pain in dogs.