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The anesthetic effects of alfaxalone were investigated in mice. Mice were administered alfaxalone (100 mg/kg) alone or the combinations of 0.3 mg/kg of medetomidine and 5 mg/kg of butorphanol with alfaxalone at doses of 20 mg/kg (M/B/A20), 40 mg/kg (M/B/A40), 60 mg/kg (M/B/A60), or 80 mg/kg (M/B/A80). Control mice received 0.3 mg/kg of medetomidine, 4 mg/kg of midazolam, and 5 mg/kg of butorphanol (M/M/B). Each drug was administrated by intraperitoneal (IP) or subcutaneous (SC) routes. M/M/B IP did not achieve surgical anesthesia but M/M/B SC achieved surgical anesthesia within 10 min after administration and maintained anesthesia for 45 min. The anesthetic scores were very low after IP or SC administration of alfaxalone alone. M/B/A20 IP and SC did not achieve surgical anesthesia. M/B/A40 IP did not achieve surgical anesthesia but M/B/A40 SC achieved surgical anesthesia within 10 min after administration and maintained anesthesia for 35 min. M/B/A60 SC achieved surgical anesthesia within 5 min after administration and maintained anesthesia for 75 min. By contrast, M/B/A60 IP did not achieve surgical anesthesia. M/B/A80 SC achieved surgical anesthesia within 5 min after administration and maintained anesthesia for 85 min. By contrast, M/B/A80 IP did not achieve surgical anesthesia and one mouse died about 10 min after drug administration. Administration of atipamezole rapidly reversed anesthesia induced by M/B/A60 in mice. These results suggest that M/B/A60 SC, an alfaxalone-based combination, is suitable for inducing surgical anesthesia in laboratory mice.

An anesthetic mixture of medetomidine (MED), midazolam (MID), and butorphanol (BUT) has been used in laboratory animals. We previously reported that this anesthetic mixture produced closely similar anesthetic effects in BALB/c and C57BL/6J strains. We also demonstrated the efficacy of atipamezole (ATI), an antagonist of MED that produced quick recovery from anesthesia in mice. Anesthetics have various anesthetic effects among animal strains. However, the differences in the effects of anesthetic mixtures in rats are unclear. In the present study, we first examined effects of the abovementioned anesthetic mixture using three different rat strains: Wistar (WST), Sprague-Dawley (SD), and Fischer 344 (F344). Second, we examined how different dosages and optimum injection timing of ATI affected recovery from anesthesia in rats. We used the anesthetic score to measure anesthetic duration and a pulse oximeter to monitor vital signs. We found no significant differences in anesthetic duration among the three different strains. However, recovery from anesthesia in the SD strain took significantly longer than in the other strains. The antagonistic effects of ATI (0.15 mg/kg and 0.75 mg/kg) were equivalent when administered at 30 min after anesthetic mixture administration. The antagonistic effects of ATI 0.75 mg/kg were stronger than those of ATI 0.15 mg/kg at 10 min after anesthetic mixture administration. This anesthetic mixture is a useful drug that can induce similar anesthetic effects in three different strains and has an antagonist, ATI, that makes rats quickly recover from anesthesia. These results may contribute to the welfare of laboratory animals.

Objective: To provide stable anaesthesia of long duration in broiler chickens in order to perform a terminal caecal ligated loop procedure., Study Design: Prospective experimental study., Animals: Seven clinically healthy broiler chickens (Gallus domesticus) aged 27-36 days, weighing 884-2000 g., Methods: Anaesthesia was induced and maintained with isoflurane in oxygen. All birds underwent intermittent positive pressure ventilation for the duration. End-tidal carbon dioxide, peripheral haemoglobin oxygen saturation, heart rate and oesophageal temperature were monitored continuously. All birds received intraosseous fluids. Butorphanol (2 mg kg(-1)) was administered intramuscularly at two hourly intervals. Euthanasia by parenteral pentobarbitone was performed at the end of procedure., Results: Stable anaesthesia was maintained in four chickens for durations ranging from 435 to 510 minutes. One bird died and one was euthanized after 130 and 330 minutes, respectively, owing to surgical complications and another died from anaesthetic complication after 285 minutes., Conclusions and Clinical Relevance: Long-term, stable anaesthesia is possible in clinically healthy chickens, provided complications such as hypothermia and hypoventilation are addressed and vital signs are carefully monitored. There are no known previous reports describing monitored, controlled anaesthesia of this duration in chickens., (© 2015 The Authors Veterinary Anaesthesia and Analgesia published by John Wiley & Sons Ltd on behalf of Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

This study evaluated anesthesia quality, degree of analgesia and cardiorespiratory parameters after intramuscular (IM) injection of a combination of butorphanol (0.1 mg/kg), medetomidine (10 µg/kg) and alfaxalone (1.5 mg/kg) in ten healthy adult Beagle dogs. Rectal temperature (T), heart rate (HR), respiratory rate (fR), arterial pressure, arterial blood gases and M-mode echocardiographic left ventricular (LV) indices were measured before drug administration and every 10 min thereafter until extubation. Mean duration of anesthesia, recovery and analgesia were 89 ± 17, 6 ± 1 and 80 ± 12 min. HR, fR, partial pressure of arterial CO2 and O2, arterial pressure, and LV contractility were significantly altered during anesthesia. IM administration of the drug combination provided acceptable anesthesia, but produced substantial cardiorespiratory suppression.

Objectives: To evaluate the echocardiographic variables and sedation after two dosages of dexmedetomidine combined with butorphanol in healthy dogs., Animals: Fourteen healthy dogs., Methods: The dogs received dexmedetomidine 5 mcg/kg IM and butorphanol 0.4 mg/kg (low dose (LD), n = 6) or dexmedetomidine 10 mcg/kg IM and butorphanol 0.4 mg/kg (recommended dose (RD), n = 8). Sedation scoring, noninvasive blood pressure measurement, and echocardiography were performed before sedation at baseline, at 20 minutes (T20), and 60 minutes (T60) after drug administration., Results: The median sedation scores were increased at both T20 and T60 in the RD group, and at T60 in the LD group, compared with baseline (p < 0.0001, p = 0.012). At T60, the RD dogs were more sedated than the LD dogs (p = 0.0093). The median cardiac output (CO) decreased at both T20 (63%) and T60 (65%) in the RD group and at T60 (42%) in the LD group, compared with baseline (p = 0.0011, p = 0.0055). The median heart rate (HR) was decreased at both T20 and T60 in the RD group and at T60 in the LD group, compared with baseline (p = 0.0009, p = 0.0001). In both RD and LD dogs, valvular regurgitation developed and was identified by color Doppler imaging., Conclusions: There were significant hemodynamic changes, mainly related to HR and indices of systolic function, following administration of dexmedetomidine in these healthy dogs. The changes also included decreases in systolic function and CO, as well as appearance of 'new' valvular regurgitation. Caution should be used when considering dexmedetomidine for sedation in dogs with, or being screened for, cardiovascular disease., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To compare the sedative effects of an intramuscular (IM) low dose of medetomidine in combination with butorphanol or methadone in dogs., Study Design: Prospective, blinded, randomized clinical trial., Animals: Forty-eight healthy adult dogs that required sedation for diagnostic or surgical elective procedures., Methods: Dogs were sedated IM with medetomidine (2.5 μg kg(-1)) and either butorphanol (0.4 mg kg(-1)) or methadone (0.4 mg kg(-1)). The degree of sedation was assessed every 10 minutes, for 30 minutes, using a numeric descriptive scale. Data on heart rate (HR), respiratory rate, capillary refill time, temperature and response to a toe pinch were recorded. The response to venous catheterization at minute 30 was also evaluated., Results: Both combinations produced moderate to deep sedation with a maximal effect at 20-30 minutes without significant differences in the degree of sedation between the treatments at any studied time-point. HR decreased from minute 10 to minute 30 with both opioid combinations (p<0.05); this reduction did not differ between groups (p>0.05). No differences between groups were detected in any of the other variables., Conclusions and Clinical Relevance: Combinations of a low dose of medetomidine with butorphanol or methadone, respectively, provide similar degrees of sedation., (© 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Ten white rhinoceros (Ceratotherium simum) were immobilized for a total of 13 procedures in holding facilities in Kruger National Park using etorphine, azaperone, and hyaluronidase to assess the effect of extended immobilization on serial cardiorespiratory, blood gas, and lactate values. Butorphanol was administered intravenously following initial blood collection and physiologic assessment (t=0). Respiratory and cardiovascular parameters, body temperature, and arterial blood gases were monitored at 10-min intervals for a total of 100 min. Initial parameters at the time of recumbency revealed severe hypoxemia, hypercapnia, tachycardia, an increased alveolar-arterial (A-a) gradient, and mildly elevated lactate levels. At 10 min and 20 min, there were significant (P<0.05) changes in the following physiologic parameters: heart rate decreased [96 and 80 beats/min, respectively, vs. 120 beats/min], arterial partial pressure of oxygen (PaO2) increased [48 and 45 mm Hg, respectively vs. 30 mm Hg], arterial hemoglobin oxygen saturation increased [79% and 74%, respectively, vs. 47%], A-a gradient decreased [29.13 and 30.00 mm Hg, respectively, vs. 49.19 mm Hg], and respiratory rate decreased [5 and 5 breaths/min vs. 7 breaths/min]. Blood lactate levels also decreased from 2.54 mM/L to 1.50 and 0.89 mM/L, respectively. Despite initial improvements in blood oxygen levels at t=10 and 20 min, the rhinoceros remained severely hypoxemic for the remainder of the procedure (median PaO2=50.5 mm Hg, 95% confidence interval, 43.8-58.1). Median values for respiratory rate (5 breaths/min) and arterial partial pressure of carbon dioxide (PaCO2; 68.5 mm Hg) did not change significantly for the remaining 80 min. Median lactate, base excess, bicarbonate, and pH values improved between 20 and 100 min despite the persistent hypercapnia, indicating that the animals adequately compensated for respiratory and lactic acidosis. White rhinoceros were immobilized for 100 min with no negative effects, a desirable outcome if procedures require extended chemical immobilization without oxygen supplementation.

Seventeen captive Nubian ibex (Capra nubiana) were immobilized for transportation and/or hoof trimming, deworming, and vaccinations. Of these, 11 were immobilized with a combination of butorphanol (0.13±0.03 mg/kg), midazolam (0.13±0.03 mg/kg), and medetomidine (0.13±0.03 mg/kg) (BMM), and 6 were immobilized with a combination of butorphanol (0.11±0.03 mg/kg), azaperone (0.22±0.06 mg/kg), and medetomidine (0.11±0.03 mg/kg) (BAM) by intramuscular injection. Induction and recovery times were recorded. Heart rate, respiratory rate, rectal temperature, blood pressure, and oxygen saturation were measured. The quality of induction, immobilization, and recovery were scored (scale 1-5; 1=poor, 5=excellent). Mean induction time was significantly shorter in the BMM group versus the BAM group (8.8±2.7 and 20.1±7.8 min, respectively). Median induction score and median immobilization score were significantly higher (i.e., better) in the BMM group than the BAM group (5 versus 2.5 and 4 versus 3, respectively). The mean and diastolic blood pressures were significantly higher in the BMM group at the 25-min time point. Atipamezole was administered at the end of procedures, and all ibex recovered smoothly. Mean recovery time was significantly longer in the BMM group versus the BAM group (9.5±4.3 and 3.3±2.2, respectively). In conclusion, at the doses used, the combination of BMM was superior to BAM for short-term immobilization in captive Nubian ibex.

Acute stress induced by physical restraint can interfere with the validity of laboratory findings. Sedation could minimize such stress. However, it is not known whether sedation can affect hematologic and hemostatic parameters in cats. The purpose of this study was to evaluate hematologic and hemostatic parameters in domestic cats subjected to physical restraint in addition to one of two sedation protocols. In total, 50 cats were subjected to physical restraint and were then randomly divided into two groups of 25 animals, receiving dexmedetomidine (5 µg/kg) and butorphanol (0.3 mg/kg; DB group) or dexmedetomidine (5 µg/kg), butorphanol (0.3 mg/kg) and ketamine (3 mg/kg; DBK group). The cats were assessed for acute stress, sedation level, onset of sedation and duration of sedation. Blood samples were collected after handling and after sedation. The complete blood count (CBC), platelet count, buccal mucosal bleeding time (BMBT), whole-blood clotting time, prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT) were determined for each sample, before and after chemical restraint. No statistically significant differences were found in the hematologic parameters. Certain hemostatic parameters (PT, aPTT and TT) were higher in the DB group (P <0.05). The onset of sedation was similar in the two groups, and the duration of sedation was longer in the DBK group. Both sedation protocols were effective for short-duration chemical restraint for blood collection from the studied cats, and no clinically relevant effects on hematologic or hemostatic parameters were detected., (© ISFM and AAFP 2014.)

Reasons for Performing Study: Combinations of α2 -adrenoceptor and opioid agonists are commonly used in equids, but little scientific information is available on donkeys., Objectives: To compare the sedative and hypoalgesic effects of xylazine alone or in combination with different dosages of butorphanol in donkeys., Study Design: Placebo-controlled, operator-blinded, randomised, crossover, Latin square study., Methods: Six donkeys received intravenous normal saline and normal saline (NS-NS); xylazine (0.5 mg/kg bwt) and normal saline (X-NS); xylazine and 10 μg/kg bwt butorphanol (X-B10); xylazine and 20 μg/kg bwt butorphanol (X-B20); xylazine and 30 μg/kg bwt butorphanol (X-B30); and xylazine and 40 μg/kg bwt butorphanol (X-B40). Sedation scores (SS), head height above ground (HHAG) and mechanical nociceptive thresholds (MNT) were assessed before and for 120 min after treatment. Areas under the curve (AUC) values for 0-30, 30-60 and 60-120 min were computed for SS, HHAG and MNT. As appropriate, differences between treatments were analysed using the Friedman test followed by Dunn's test and a repeated measures one-way analysis of variance followed by Tukey's test; significance was set at P<0.05., Results: All treatments apart from NS-NS induced sedation. Butorphanol treatments induced significantly larger SS-AUC0 -30 values than those for NS-NS (P<0.05). Compared to corresponding NS-NS values, HHAG-AUC0 -30 values were significantly smaller for all other treatments (P<0.001) and HHAG-AUC30-60 values were significantly smaller for X-B40 (P<0.05). Compared to NS-NS, all treatments induced mechanical hypoalgesia and yielded significantly larger MNT-AUC0-30 values (P<0.001). Treatment X-NS yielded significantly smaller MNT-AUC0 -30 values than those for X-B30 and X-B40 (P<0.05). Only MNT-AUC30 -60 values for X-B30 and X-B40 were significantly larger than those for NS-NS and X-NS (P<0.05)., Conclusions: Sedation and mechanical hypoalgesia induced by xylazine were enhanced by butorphanol at 40 μg/kg bwt. This drug combination may be suitable for chemical restraint of donkeys undergoing certain clinical procedures., (© 2014 EVJ Ltd.)

Objective: To evaluate the physiological variables, arterial blood gas values, induction of anesthesia quality, and recovery quality using the combination of butorphanol, midazolam and alfaxalone in dogs., Animals: Ten healthy adult Beagle dogs weighing 8.3 ± 3.1 kg., Methods: Rectal temperature (T), pulse rate (PR), respiratory rate (f(R)), mean arterial pressure (MAP), and arterial blood gases were measured and recorded prior to intravenous (IV) administration of butorphanol, prior to administration of both midazolam and alfaxalone IV 10 minutes later, then every 5 minutes for 20 minutes. M-mode echocardiographic left ventricular (LV) indices were measured before and 5 minutes after administration of alfaxalone. Qualitative scores for induction of anesthesia and recovery were allocated, duration of anesthesia and recovery were calculated, and adverse events were recorded., Results: Scores for induction and recovery quality were excellent. No significant adverse events were observed. Mean ± SD time from induction to extubation and to standing (full recovery) was 29 ± 6 and 36 ± 8 minutes, respectively. There were statistically significant changes in PR, f(R) and MAP after drug administration. Transient hypercarbia developed after alfaxalone injection. The echocardiographic LV indices were reduced after alfaxalone injection, although those changes were not statistically significant., Conclusions and Clinical Relevance: The combination of butorphanol, midazolam and alfaxalone provided excellent quality of induction of anesthesia and exerted minimal cardiopulmonary effects in healthy dogs., (© 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Opioid receptors in the central nervous system are important modulators of itch transmission. In this study, we examined the effect of mixed-action opioid butorphanol on histamine itch, cowhage itch, and heat pain in healthy volunteers. Using functional MRI, we investigated significant changes in cerebral perfusion to identify the critical brain centers mediating the antipruritic effect of butorphanol. Butorphanol suppressed the itch induced experimentally with histamine, reduced the intensity of cowhage itch by approximately 35%, and did not affect heat pain sensitivity. In comparison with the placebo, butorphanol produced a bilateral deactivation of claustrum, insula, and putamen, areas activated during itch processing. Analysis of cerebral perfusion patterns of brain processing of itch versus itch inhibition under the effect of the drug revealed that the reduction in cowhage itch by butorphanol was correlated with changes in cerebral perfusion in the midbrain, thalamus, S1, insula, and cerebellum. The suppression of histamine itch by butorphanol was paralleled by the activation of nucleus accumbens and septal nuclei, structures expressing high levels of kappa opioid receptors. In conclusion, important relays of the mesolimbic circuit were involved in the inhibition of itch by butorphanol and could represent potential targets for the development of antipruritic therapy.

Isoflurane is a representative inhalant anesthesia used in laboratory animals. However, isoflurane mediates respiratory depression and adverse clinical reactions during induction. In the present study, we established a novel balanced anesthesia method in mice that combined isoflurane anesthesia with midazolam and butorphanol (MB). Thirty-four male C57BL/6J mice received either isoflurane alone or isoflurane with an intra-peritoneal MB premedication (3 mg/kg midazolam and 4 mg/kg butorphanol). The minimum alveolar concentration (MAC) in each group was evaluated. Induction time and adverse clinical reactions were recorded in each group. Core body temperature, heart rate, respiratory rate, and oxygen saturation (SPO(2)) were assessed before and for 1 h after induction. Premedication with MB achieved a significant reduction in MAC compared with isoflurane monoanesthesia (isoflurane, 1.38 ± 0.15%; isoflurane with MB, 0.78 ± 0.10%; P<0.05). Induction time was significantly shortened with MB premedication, and adverse reactions such as excitement or incontinence were observed less frequently. Furthermore, isoflurane anesthesia with MB premedication caused increase of respiratory rates compared to isoflurane monoanesthesia. No significant decrease of SPO(2) was observed in MBI anesthesia, while a decrease in SPO(2) was apparent with isoflurane monoanesthesia (baseline, 98.3% ± 1.1; 10 min after induction, 91.8 ± 6.4%; P<0.05). In conclusion, premedication with MB was effective for the mitigation of respiratory depression induced by isoflurane in mice, with rapid induction and fewer adverse clinical reactions.

The anesthetic mixture of medetomidine (MED), midazolam (MID) and butorphanol (BUT) produced anesthetic duration of around 40 minutes (min) in ICR mice. We reported that this anesthetic mixture produced almost the same anesthetic effects in both male and female BALB/c and C57BL/6J strains. Intraperitoneal (IP) administration of drugs has been widely used in mice. However, various injectable routes of the anesthetic mixture may cause different anesthetic effects. First, we examined effects of the anesthetic mixture by subcutaneous (SC) and intravenous (IV) injection compared to IP injection. After injection of the anesthetic mixture, administration of atipamezole (ATI) induced mice recovery from anesthesia. Secondly, we examined how different dosage and optimum injection timing of ATI affected mice recovery from anesthesia. We used an anesthetic score to measure anesthetic duration and a pulse oximeter to monitor vital signs under anesthesia. Usually, drugs from SC injection work more weakly than IP or IV injection. However, we found no significant differences of anesthetic duration among the three different injection routes. Antagonistic effects of ATI (0.3 mg/kg and 1.5 mg/kg) worked equally when administered at 30 min after injection of the anesthetic mixture. Antagonistic effects of ATI (1.5 mg/kg) were stronger than ATI (0.3 mg/kg) at 10 min after injection of the anesthetic mixture. The anesthetic mixture is a useful drug to induce nearly the same anesthetic effects by different injection routes and has an antagonist of ATI which helps mice quickly recover from anesthesia. These results may contribute to the welfare of laboratory animals.

Effects of intermittent positive pressure ventilation (IPPV) on cardiopulmonary function were evaluated in horses anesthetized with total intravenous anesthesia using constant rate infusions of medetomidine (3.5 µg/kg/hr), lidocaine (3 mg/kg/hr), butorphanol (24 µg/kg/hr) and propofol (0.1 mg/kg/min) (MLBP-TIVA). Five horses were anesthetized twice using MLBP-TIVA with or without IPPV at 4-week interval (crossover study). In each occasion, the horses breathed 100% oxygen with spontaneous ventilation (SB-group, n=5) or with IPPV (CV-group, n=5), and changes in cardiopulmonary parameters were observed for 120 min. In the SB-group, cardiovascular parameters were maintained within acceptable ranges (heart rate: 33-35 beats/min, cardiac output: 27-30 l/min, mean arterial blood pressure [MABP]: 114-123 mmHg, mean pulmonary arterial pressure [MPAP]: 28-29 mmHg and mean right atrial pressure [MRAP]: 19-21 mmHg), but severe hypercapnea and insufficient oxygenation were observed (arterial CO(2) pressure [PaCO(2)]: 84-103 mmHg and arterial O(2) pressure [PaO(2)]: 155-172 mmHg). In the CV-group, normocapnea (PaCO(2): 42-50 mmHg) and good oxygenation (PaO(2): 395-419 mmHg) were achieved by the IPPV without apparent cardiovascular depression (heart rate: 29-31 beats/min, cardiac output: 17-21 l /min, MABP: 111-123 mmHg, MPAP: 27-30 mmHg and MRAP: 15-16 mmHg). MLBP-TIVA preserved cardiovascular function even in horses artificially ventilated.

Purpose: To assess the cardiorespiratory parametes, recovery, gastrointestinal motility and serum cortisol concentrations in horses anesthetized with isoflurane with or without a continuous rate infusion (CRI) of butorphanol for orchiectomy., Methods: Twelve adult, intact, male horses weighing 332 ± 55 kg were included in the study. Xilazine was administered as premedication. Anesthesia was induced with ketamine and midazolam and maintained with isoflurane. Butorphanol (0.025 mg kg-1 bolus) or an equivalent volume of saline (0.9%) was given intravenously followed by a CRI of butorphanol (BG) (13 µg kg-1 hour-1) or saline (CG). Cardiorespiratory variables were recorded before (T0) and every 15 minutes for 75 minutes after the start of infusion. Serum cortisol concentration was measured at T0 and 60 minutes, and 30 minutes and 19 hours after the horse stood up. Recovery from anesthesia was evaluated using a scoring system. Gastrointestinal motility was evaluated before anesthesia and during 24 hours after recovery., Results: There were no significant differences between groups in cardiopulmonary variables, or recovery scores or serum cortisol concentrations. A reduction in gastrointestinal motility was recorded for 60 minutes in BG., Conclusions: Continuous rate infusion of butorphanol in horses anesthetized with isoflurane did not adversely affect the cardiopulmonary variables monitored, or recovery scores. A small but statistically significant reduction in gastrointestinal motility occurred in the butorphanol group.

Contrast-enhanced ultrasonography of the left kidney was performed using a commercial contrast agent in six healthy adult purpose-bred cats. A cross-over design was used to compare three protocols: (1) awake, (2) butorphanol (0.4 mg/kg IM), and (3) propofol (3.5-7.7 mg/kg IV boluses to effect). Time-intensity curves were created from two regions-of-interest drawn in the renal cortex. The curves were analyzed for blood flow parameters representing blood volume (base intensity, peak intensity, area-under-curve) and blood velocity (arrival time, time-to-peak, wash-in/out). There was no difference in the subjective enhancement pattern between the three protocols. No significant effect of butorphanol was observed in any of the perfusion parameters (P > 0.05). Propofol did not influence the most important perfusion parameter, area-under-the-curve, and is adequate for use in contrast-enhanced ultrasound studies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To compare the cardiopulmonary effects of intravenous (IV) and intramuscular (IM) medetomidine and butorphanol with or without MK-467., Study Design: Prospective, randomized experimental cross-over., Animals: Eight purpose-bred beagles (two females, six males), 3-4 years old and weighing 14.5 ±1.6 kg (mean ± SD)., Methods: All dogs received four different treatments as follows: medetomidine 20 μg kg(-1) and butorphanol tartrate 0.1 mg kg(-1) IV and IM (MB), and MB combined with MK-467,500 μg kg(-1) (MBMK) IV and IM. Heart rate (HR), arterial blood pressures (SAP, MAP, DAP), central venous pressure (CVP), cardiac output, respiratory rate (fR ), rectal temperature (RT) were measured and arterial blood samples were obtained for gas analysis at baseline and at 3, 10, 20, 30, 45 and 60 minutes after drug administration. The cardiac index (CI), systemic vascular resistance index (SVRI) and oxygen delivery index (DO2 I) were calculated. After the follow-up period atipamezole 50 μg kg(-1) IM was given to reverse sedation., Results: HR, CI and DO2 I were significantly higher with MBMK after both IV and IM administration. Similarly, SAP, MAP, DAP, CVP, SVRI and RT were significantly lower after MBMK than with MB. There were no differences in fR between treatments, but arterial partial pressure of oxygen decreased transiently after all treatments. Recoveries were uneventful following atipamezole administration after all treatments., Conclusions and Clinical Relevance: MK-467 attenuated the cardiovascular effects of a medetomidine-butorphanol combination after IV and IM administration., (© 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

There have been recent calls to examine the efficacy of drug-combination therapies in the treatment of substance use disorders. The purpose of the present study was to examine the ability of a novel stimulant-opioid combination to reduce cocaine self-administration, and to compare these effects to those of each drug administered alone. To this end, male Long-Evans rats were implanted with intravenous catheters and trained to self-administer cocaine under positive reinforcement contingencies. Once self-administration was acquired, rats were divided into four different groups and treated chronically for 20 days with (1) saline, (2) the psychomotor stimulant and monoamine releaser amphetamine, (3) the mu/kappa opioid agonist butorphanol, or (4) a combination of amphetamine and butorphanol. During chronic treatment, cocaine self-administration was examined on both fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. On the FR schedule, butorphanol significantly decreased cocaine self-administration, but this effect was not enhanced by amphetamine. On the PR schedule, amphetamine and butorphanol non-significantly decreased cocaine self-administration when administered alone but significantly decreased cocaine self-administration when administered in combination. These data suggest that under some conditions (e.g., when the response requirement of cocaine is high), a dual stimulant-opioid pharmacotherapy may be more effective than a single-drug monotherapy., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We formulated novel drug combinations of nalbuphine HCl and medetomidine HCl (NalMed), with or without azaperone tartrate, for use in immobilizing Rocky Mountain elk (Cervus elaphus nelsoni) and potentially for other wildlife species. Using the lowest tested nalbuphine dose (0.3 mg/kg) that produced sedation in elk, we initially evaluated a combination of nalbuphine, medetomidine, and azaperone (NalMed-A) for immobilizing adult elk. Based on initial success, we then conducted follow-up trials to assess alternative NalMed formulations successively modified to improve field usability, striving to shorten induction within a dose volume that accommodated practical remote delivery. All NalMed formulations immobilized adult elk; however, combinations with dose volumes that included about 80 mg nalbuphine tended to yield the shortest inductions (mean 6.8 min with, and 7.7 min without, azaperone). Our findings demonstrate that nalbuphine and medetomidine can be combined to yield effective, low-volume (≤ 2 mL), lightly regulated, reversible drug combinations. Based on results to date, we recommend NalMed-A (40 mg/mL nalbuphine, 10 mg/mL medetomidine, and 10 mg/mL azaperone) dosed at 1.8-2.0 mL for immobilizing adult elk; for recovery we recommend 50 mg naltrexone and 600 mg tolazoline administered intramuscularly (IM) about 5 min in advance of 100 mg atipamezole (divided 25 mg intravenously and 75 mg IM). Further work is under way to explore efficacy in other large mammal species.

Abstract We report the clinical course and physiologic and anesthetic data for a case series of 76 free-ranging dromedary camels (Camelus dromedarius) chemically restrained, by remote injection from a helicopter, in the rangelands of Western Australia and South Australia, 2008-11, to attach satellite-tracking collars. Fifty-five camels were successfully anesthetized using medetomidine-ketamine (MK, n=27) and medetomidine-ketamine-butorphanol (MKB, n=28); the induction of anesthesia in 21 animals was considered unsuccessful. To produce reliable anesthesia for MK, medetomidine was administered at 0.22 mg/kg (± SD=0.05) and ketamine at 2.54 mg/kg (± 0.56), and for MKB, medetomidine was administered at 0.12 mg/kg (± 0.05), ketamine at 2.3 mg/kg (± 0.39), and butorphanol at 0.05 mg/kg (± 0.02). Median time-to-recumbency for MKB (8.5 min) was 2.5 min shorter than for MK (11 min) (P=0.13). For MK, the reversal atipamezole was administered at 0.24 mg/kg (± 0.10), and for MKB, atipamezole was administered at 0.23 mg/kg (± 0.13) and naltrexone at 0.17 mg/kg (± 0.16). Median time-to-recovery was 1 min shorter for MK (5 min) than MKB (6 min; P=0.02). Physiologic parameters during recumbency were not clinically different between the two regimes. Both regimes were suitable to safely anesthetize free-ranging camels; however, further investigation is required to find the safest, most consistent, and logistically practical combination.

Abstract We immobilized 47 white rhinoceroses (Ceratotherium simum) for dehorning with 1-4 mg of etorphine HCl, 10-40 mg of azaperone, and 7,500 IU of hyaluronidase, at a game ranch in South Africa in November 2012. Forty-four received butorphanol intravenously 5 min after recumbency, at the rate of 10 mg of butorphanol per 1 mg of etorphine, and three animals did not. When possible, blood gas and physiologic parameters were measured immediately before butorphanol administration and 10 min later. Statistically significant improvements were observed, with a reduction in pH, partial pressure of carbon dioxide in arterial blood, heart rate, systolic blood pressure, and diastolic blood pressure, and with an increase in arterial partial pressure of oxygen, arterial hemoglobin oxygen saturation, and respiratory rate in animals administered butorphanol. In the three animals that did not receive butorphanol, no improvement was apparent. Butorphanol given to recumbent white rhinoceroses immediately after immobilization was associated with improved blood gas values and cardiopulmonary function for at least 10 min. Studies on the sustainability of these effects are necessary.

This randomized, double-blinded, placebo-controlled trial investigated the effect of continuous epidural butorphanol on intrathecal morphine-related pruritus in patients undergoing cesarean section. Eighty-three patients undergoing elective cesarean section under spinal anesthesia (1.5 mL of isobaric bupivacaine 0.5 % and 0.1 mg of preservative-free morphine) were enrolled in this study. Subjects were randomized to receive epidural butorphanol (n = 43) or normal saline combined bupivacaine (n = 40). In the study group, after the umbilical cord was clamped, patients were administered an epidural loading dose of 1 mg followed by a 48-h infusion of 0.004 % butorphanol with 0.1 % bupivacaine at a rate of 2 mL/h. In the normal saline group, saline was used for the loading dose and the infusion 0.1 % bupivacaine at a same rate. Postoperatively, a blinded observer recorded the incidence/severity of pruritus, visual analog pain scores and sedation level at 1, 3, 6, 9, 12, 24 and 48 h. The 48-h consumption of breakthrough analgesic (tramadol) was also noted. The primary outcome was the incidence of pruritus at 48 h. At 48 h, the incidence of pruritus was significantly lower in the butorphanol group (16.3 vs. 52.5 %; P < 0.001). Furthermore, compared with the normal saline group, the intensity of pruritus was also decreased with epidural butorphanol at 3, 6 and 9 h (all P ≤ 0.008). The pain scores were significantly lower at 12, 24 and 48 h (all P < 0.05) in the butorphanol groups. Patients only receiving bupivacaine required a higher cumulative dose of tramadol (37.5 ± 62.8 vs. 9.3 ± 36.6; P = 0.014). In patients undergoing elective cesarean section, continuous epidural butorphanol with bupivacaine decreases the incidence and severity of intrathecal morphine-related pruritus without adversely affecting the quality of postoperative analgesia.

Goats are rarely anaesthetised; consequently, scant information is available on the efficacy of anaesthetic drugs in this species. Alfaxalone is a relatively new anaesthetic agent, of which the efficacy in goats has not yet been studied. In this study, the sedative and alfaxalone sparing effects of midazolam and butorphanol, administered alone or concomitantly, in goats were assessed. Eight clinically healthy goats, four does and four wethers, were enlisted in a randomised crossover manner to receive intramuscular sedative treatments consisting of saline 0.05 mL/kg, or midazolam 0.30 mg/kg, or butorphanol 0.10 mg/kg, or a combination of midazolam 0.30 mg/kg with butorphanol 0.10 mg/kg before intravenous induction of general anaesthesia with alfaxalone. Following induction, the goats were immediately intubated and the quality of anaesthesia and basic physiological cardiorespiratory and blood-gas parameters were assessed until the goats had recovered from anaesthesia. The degree of sedation, quality of induction and recovery were scored. When compared with saline (3.00 mg/kg), midazolam,administered alone or with butorphanol, caused a statistically significant increased level of sedation and a reduction in the amount of alfaxalone required for induction (2.00 mg/kg and 1.70 mg/kg, respectively). Butorphanol alone (2.30 mg/kg) did not cause significant changes in level of sedation or alfaxalone-induction dose. During induction and recovery, the goats were calm following all treatments, including the control group. Cardiorespiratory and blood-gas parameters were maintained within clinically acceptable limits. The present study showed that midazolam, administered alone or combined with butorphanol, produces a degree of sedation that significantly reduces the dose of alfaxalone required for induction of general anaesthesia in goats, without causing any major adverse cardiorespiratory effects.

We compared dosages of a combination of sedatives, which included butorphanol tartrate, azaperone tartrate, and medetomidine HCl (BAM) in captive adult Rocky Mountain elk (Cervus elaphus nelsoni). All three BAM dosages (low, medium, and high) effectively immobilized elk and produced an adequate level of sedation in all subjects. Induction times were similar among the three groups (mean ± SD: low=6.9 ± 1.1 min; medium=6.3 ± 0.9 min; high=4.7 ± 1.3 min). Most elk became hypoxemic regardless of BAM dosage, but hypoxemia tended to be most severe in the high-BAM group; regardless of BAM dosage, oxygen supplementation improved the percentage of oxygen saturation and stabilized the vital rates. Recovery after administration of antagonists (3 mg atipamezole/mg medetomidine and 2 mg/kg tolazoline) was comparable among groups (range of means=9 ± 1.5-11.7 ± 1 min). Based on the findings from clinical trials and field data from free-ranging elk immobilizations, we recommend low-dose BAM (2 mL dose; equivalent to 46 mg butorphanol, 30 mg azaperone, and 18 mg medetomidine) and supplemental oxygen for adult elk; immobilization should be antagonized using 3-5 mg atipamezole/mg medetomidine and 2 mg/kg tolazoline, with tolazoline injected about 5-10 min before atipamezole to smooth out recovery.

Three medetomidine-based protocols were evaluated for sedation in companion rats undergoing diagnostic procedures. Group Me received medetomidine at 150 μg/kg intramuscularly (IM); group Me-Bu received medetomidine 100 μg/kg IM and butorphanol 2 mg/kg IM, and group Me-Bu-Mi received medetomidine 50 μg/kg IM, butorphanol 2 mg/kg IM and midazolam 1 mg/kg IM. The righting reflex disappeared more quickly in the Me-Bu-Mi group, but recovery after atipamezole was longer. In group Me, a palpebral reflex was present throughout sedation in more rats than in the other two groups. Pulse and respiratory rates were higher when lower doses of medetomidine were used, although arterial haemoglobin O2 saturation was similar among groups. All protocols tested produced adequate sedation lasting 25 min., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The anesthetic effect of a combination of medetomidine, midazolam and butorphanol (Me-Mi-Bu) was evaluated in healthy cynomolgus monkeys. The Me-Mi-Bu combination was intramuscularly administered as follows: Dose 1, Me 0.015 mg/kg-Mi 0.1 mg/kg-Bu 0.15 mg/kg; Dose 2, Me 0.02 mg/kg-Mi 0.15 mg/kg-Bu 0.2 mg/kg; and Dose 3, Me 0.04 mg/kg-Mi 0.3 mg/kg-Bu 0.4 mg/kg. The combination rapidly induced immobilization, and lateral recumbency was reached within 15 min. The duration of anesthesia for each dose administered was follows: Dose 1, 47 ± 27 min; Dose 2, 113 ± 31 min; and Dose 3, 190 ± 24 min. The anesthetic effect of the combination was abolished by the α2-adrenoceptor antagonist atipamezole. No marked changes in the levels of hematologic or serum biochemical parameters were noted in cynomolgus monkeys administered the combination plus atipamezole. Taken together, these results suggest that the Me-Mi-Bu combination exhibits reversible anesthetic effect and may be useful for studies involving cynomolgus monkeys.

Lameness is common in commercially reared broiler chickens but relationships between lameness and pain (and thus bird welfare) have proved complex, partly because lameness is often partially confounded with factors such as bodyweight, sex and pathology. Thermal nociceptive threshold (TNT) testing explores the neural processing of noxious stimuli, and so can contribute to our understanding of pain. Using an acute model of experimentally induced articular pain, we recently demonstrated that TNT was reduced in lame broiler chickens, and was subsequently attenuated by administration of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). This study extended these findings to a large sample of commercial broilers. It examined factors affecting thermal threshold (Part 1) and the effect of an NSAID drug (meloxicam, 5 mg/kg) and of an opioid (butorphanol; 4 mg/kg) (Part 2). Spontaneously lame and matched non-lame birds (n=167) from commercial farms were exposed to ramped thermal stimulations via a probe attached to the lateral aspect of the tarsometatarsus. Baseline skin temperature and temperature at which a behavioural avoidance response occurred (threshold) were recorded. In Part 1 bird characteristics influencing threshold were modelled; In Part 2 the effect of subcutaneous administration of meloxicam or butorphanol was investigated. Unexpectedly, after accounting for other influences, lameness increased threshold significantly (Part 1). In Part 2, meloxicam affected threshold differentially: it increased further in lame birds and decreased in non-lame birds. No effect of butorphanol was detected. Baseline skin temperature was also consistently a significant predictor of threshold. Overall, lameness significantly influenced threshold after other bird characteristics were taken into account. This, and a differential effect of meloxicam on lame birds, suggests that nociceptive processing may be altered in lame birds, though mechanisms for this require further investigation.

Objectives: Butorphanol tartrate is a synthetic opioid partial agonist analgesic. Butorphanol targets the heart, mainly via κ-opioid receptor (κ-OR) activation. The purpose of this study was to determine the effect and mechanism underlying butorphanol postconditioning (B-Post) on myocardial ischaemia reperfusion injury in rats., Methods: Seventy-five male Sprague-Dawley rats were randomly divided into five groups of 15 each: Group sham; Group I/R (ischaemia/reperfusion); Group B (butorphanol postconditioning); Group B/N (butorphanol postconditioning + antagonist of κ-OR nor-binaltorphimine [Nor-BNI]); Group B/G (butorphanol postconditioning + nonselective ATP-sensitive potassium (KATP) channel blocker glibenclamide [GLI]). The left coronary anterior descending artery (LAD) was occluded for 30 min, followed by a 120-min reperfusion. Blood samples were obtained at the end of reperfusion for determination of serum tumour necrosis factor (TNF)-α and interleukin (IL)-6 concentrations. The hearts were then excised for determination of myocardial infarct size by triphenyltetrazolium chloride staining. The myocardial tissues were used for determination of the expression of myocardial superoxide dismutase (SOD), malondialdehyde (MDA) and myeloperoxidase (MPO)., Results: Myocardial infarct size was significantly reduced in B (26.4 ± 1.83%), B/N (34.5 ± 1.56%) and B/G (31.5 ± 1.27%) Groups compared with Group I/R (46.8 ± 1.41%) (all P < 0. 001). The serum TNF-α and IL-6 concentrations and the MDA and MPO activities in the ischaemic area in B, B/N and B/G Groups were significantly lower than those in the I/R Group (all P < 0.001). In addition, myocardial infarct size, TNF-α and IL-6 concentrations and the MDA and MPO activities in B/N and B/G Groups were higher than those in the B Group (all P < 0.001). In contrast, SOD activity was significantly increased in B, B/N and B/G Groups, and SOD activity in B/N and B/G Groups was less than in the B Group (all P < 0.001)., Conclusions: These results suggest that postconditioning of butorphanol tartrate can provide a potent cardioprotective effect against myocardial ischaemic and reperfusion injury. Both the κ-OR and the KATP channels were involved in this effect.

Objective: To compare the haemodynamic effects of three premedicant regimens during propofol-induced isoflurane anaesthesia., Study Design: Prospective, randomized cross-over study., Animals: Eight healthy purpose-bred beagles aged 4 years and weighing mean 13.6 ± SD 1.9 kg., Methods: The dogs were instrumented whilst under isoflurane anaesthesia prior to each experiment, then allowed to recover for 60 minutes. Each dog was treated with three different premedications given intravenously (IV): medetomidine 10 μg kg⁻¹ (MED), medetomidine 10 μg kg⁻¹ with MK-467 250 μg kg⁻¹ (MMK), or acepromazine 0.01 mg kg⁻¹ with butorphanol 0.3 mg kg⁻¹ (AB). Anaesthesia was induced 20 minutes later with propofol and maintained with isoflurane in oxygen for 60 minutes. Heart rate (HR), cardiac output, arterial blood pressures (ABP), central venous pressure (CVP), respiratory rate, inspired oxygen fraction, rectal temperature (RT) and bispectral index (BIS) were measured and arterial and venous blood gases analyzed. Cardiac index (CI), systemic vascular resistance index (SVRI), oxygen delivery index (DO₂ I), systemic oxygen consumption index (VO₂ I) and oxygen extraction (EO₂) were calculated. Times to extubation, righting, sternal recumbency and walking were recorded. The differences between treatment groups were evaluated with repeated measures analysis of covariance., Results: HR, CI, DO₂ I and BIS were significantly lower with MED than with MMK. ABP, CVP, SVRI, EO₂, RT and arterial lactate were significantly higher with MED than with MMK and AB. HR and ABP were significantly higher with MMK than with AB. However, CVP, CI, SVRI, DO₂ I, VO₂ I, EO₂, T, BIS and blood lactate did not differ significantly between MMK and AB. The times to extubation, righting, sternal recumbency and walking were significantly shorter with MMK than with MED and AB., Conclusions and Clinical Relevance: MK-467 attenuates certain cardiovascular effects of medetomidine in dogs anaesthetized with isoflurane. The cardiovascular effects of MMK are very similar to those of AB., (© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Three adult and two subadult greater one-horned rhinoceroses (Rhinoceros unicornis) were sedated a total of nine times using two different intramuscular sedative combinations in order to compare the effectiveness of these combinations in inducing consistent standing sedation in this species. The sedation protocols compared were butorphanol tartrate (50-60 mg) and detomidine hydrochloride (20-30 mg; BD) versus butorphanol tartrate (80-120 mg) and azaperone (80-120 mg; BA). Specific doses were adjusted according to age and sex class, and based on previous experience. Parameters compared included time to achieve defined levels of sedation, time to recovery following antagonism, physiological parameters including heart rate, respiratory rate, indirect arterial blood pressure, and venous blood gas values. A hydraulic restraint chute was utilized to mechanically restrain animals during the procedures, and blood collection and ophthalmic examinations were conducted on all animals. Both protocols resulted in standing sedation for > or = 22.3 +/- 2.9 min or until antagonists were administered. The BD protocol resulted in deeper and more consistent sedation, compared to the BA protocol. Naltrexone hydrochloride (250-300 mg) and tolazoline hydrochloride (1,500-2,000 mg) were administered intramuscularly to antagonize protocol BD, whereas naltrexone alone (200-500 mg) was used to antagonize BA. Time to full antagonism, defined as normal mentation and ambulation following administration of antagonists, was prolonged in the BD protocol (132.3 +/- 17.2 min) compared with the BA protocol (7.5 +/- 2.5 min). Venous blood gas analysis did not reveal any significant blood gas deviations during sedation when compared with either conscious equine or white rhinoceros (Ceratotherium simum) venous reference ranges. In summary, both combinations resulted in adequate standing sedation for minimally invasive procedures, although BD resulted in more profound and consistent sedation.

Background: Prolonged drug infusions are used to treat horses with severe signs of pain, but can be associated with altered gastrointestinal transit. The purpose of this study was to determine the effects of prolonged constant rate infusions (CRI) of lidocaine (L), butorphanol (B), and ketamine (K) alone and in combination on gastrointestinal transit, behavior, and thermal nociceptive threshold in healthy horses., Methods: Eight healthy adult horses were used in a randomized, cross-over, blinded, prospective experimental trial. Interventions were saline, L, K, B, LK, LB, BK, and LBK as an intravenous CRI for 96 hours. Drugs were mixed or diluted in saline; following a bolus, CRI rate was 0.15 mL/kg/hr with drug doses as follows: L - 1.3 mg/kg then 3 mg/kg/hr; B - 0.018 mg/kg then 0.013 mg/kg/hr; K - 0.55 mg/kg then 0.5 mg/kg/hr. Two-hundred plastic beads were administered intragastrically by nasogastric tube immediately prior to the bolus. Feces were collected every 2 hours, weighed, and beads manually retrieved. Behavior was scored every 2 hours, vital parameters every 6 hours, and thermal nociceptive threshold every 12 hours for 96 hours. Drug concentrations in the LBK solution were tested every 6 hours for 72 hours., Results: Four of 64 trials (3 LBK, 1 BK) were discontinued early due to signs of abdominal discomfort. There were no apparent differences between groups in vital parameters or thermal threshold. Transit time was delayed for LB and LBK with a corresponding decrease in fecal weight that was most severe in the final 24 hours of infusion. Significant changes in behavior scores, vital parameters, or thermal threshold were not observed. The concentration of each drug in the combined solution declined by less than 31% over the sampling period., Conclusions: Drug combinations containing butorphanol cause an apparent delay in gastrointestinal transit in healthy horses without substantially affecting somatic nociception at the doses studied. Combinations of lidocaine and ketamine may have less impact on gastrointestinal transit than infusions combined with butorphanol. Further work is needed to determine the effects of these drugs in painful or critically ill patients.

Objective: To evaluate the efficacy and safety of a combination of dexmedetomidine, butorphanol, and midazolam administered IM for anesthesia in captive Asian small-clawed otters (Aonyx cinereus) and to compare this combination with a combination of ketamine and midazolam., Design: Prospective crossover study., Animals: 10 captive Asian small-clawed otters., Procedures: A combination of either dexmedetomidine (0.03 mg/kg [0.014 mg/lb]), butorphanol (0.2 mg/kg [0.091 mg/lb]), and midazolam (0.15 mg/kg [0.068 mg/lb]) or ketamine (10.1 mg/kg [4.59 mg/lb]) and midazolam (0.3 mg/kg [0.14 mg/lb]) was administered IM to otters for immobilization to allow scheduled wellness examinations. Otters were intubated and administered 100% oxygen during the examination. Anesthesia was supplemented with isoflurane in oxygen if necessary. Routine medical procedures, including blood collection, radiography, echocardiography, dental scaling, vaccinations, and contraception administration, were performed as indicated during the immobilization. Physiologic, clinicopathologic, and anesthetic variables were recorded and compared. Otters given dexmedetomidine-butorphanol-midazolam were administered atipamezole (0.2 mg/kg [0.091 mg/lb]), naltrexone (0.6 mg/kg [0.27 mg/lb]), and flumazenil (0.05 mg/kg [0.023 mg/lb]) IM at the completion of the examination., Results: The need for and duration of isoflurane administration were greater for ketamine-midazolam anesthesia, compared with dexmedetomidine-butorphanol-midazolam anesthesia. Recoveries were shorter and subjectively smoother with dexmedetomidine-butorphanol-midazolam. Heart rates were significantly higher during ketamine-midazolam anesthesia. Regardless of protocol, all otters developed hypothermia and hypercapnia during anesthesia., Conclusions and Clinical Relevance: Both protocols were safe and effective for this species, but the reversible nature of dexmedetomidine-butorphanol-midazolam resulted in more rapid recoveries than did ketamine-midazolam. Otters anesthetized with ketamine-midazolam may require additional anesthetic medications for routine examinations, and assisted ventilation and thermal support may be of benefit with either protocol.

Voiding urohydropropulsion and cystoscopy are routine procedures performed in the dog for diagnostic and therapeutic purposes. These procedures are typically performed under general anesthesia. The purpose of this study was to describe the use of medetomidine-based sedation protocols to perform voiding urohydropropulsion and cystoscopy in cardiovascularly healthy, non-diabetic dogs without evidence of urinary obstruction, renal disease, or hepatic disease. Results of this study revealed significantly shorter procedure times and decreased cost in sedated dogs, with diagnostic and therapeutic outcomes equivalent to those of patients that underwent general anesthesia. Based on the results of this retrospective study, the authors recommend medetomidine-based sedation protocols for voiding urohydropropulsion and cystoscopy in appropriately selected patients.

Background: Sedation is commonly used during intradermal testing (IDT). Morphine and its derivatives have long been avoided because of their histamine-releasing effects., Hypothesis/objectives: Butorphanol, an opioid agonist/antagonist, will not adversely affect IDT in dogs., Animals: Ten client-owned dogs diagnosed with atopic dermatitis., Methods: Dogs were randomized to be sedated with butorphanol (0.4 mg/kg) or dexmedetomidine (5 μg/kg). Routine IDT along with intradermal injections of various dilutions of histamine were performed on the lateral thorax, followed 7 days later by the alternative sedative and IDT on the opposite side. The injection sites were subjectively scored and objectively measured by one investigator, blinded to the sedatives, and compared between groups., Results: When the mean wheal diameters from the objective measurements of all antigens, including saline and histamine dilutions, were compared, butorphanol was associated with significantly smaller reactions than dexmedetomidine (P = 0.0001). There was a high level of agreement between sedatives when positive reactions subjectively scored as ≥3+ were compared (κ = 0.91). When mean wheal diameters of histamine at concentrations of 1:100,000, 1:400,000, 1:1,600,000 and 1:6,400,000 were compared, there were no significant differences between sedative types. Moreover, the percentage agreement when comparing subjective interpretation of all histamine dilutions between sedations was high (κ = 0.90). However, there was only 69% agreement beyond chance when objective and subjective interpretations of all antigens were compared between sedative groups., Conclusions: Although butorphanol resulted in significantly smaller wheal size in comparison to dexmedetomidine, it did not affect the overall subjective interpretation of the results of IDT., (© 2013 ESVD and ACVD.)

The study was designed to determine the effects of two protocols of sedation, medetomidine and medetomidine-butorphanol, on cerebral blood flow (CBF) by transcranial color-coded Duplex ultrasonography in healthy dogs. Transcranial Doppler ultrasonographic examination was performed in 20 dogs before and 20 min after sedation with either medetomidine (group 1) or medetomidine-butorphanol (group 2). The left and right middle cerebral arteries (LMCA and RMCA) were evaluated using the temporal windows, and the basilar artery (BA) was studied through the suboccipital window. Peak systolic velocity (PSV), mean velocity (MV), end diastolic velocity (EDV), resistance index (RI), and pulsatility index (PI) were measured for each vessel. Blood pressure (BP) and heart rate (HR) were also recorded before and after sedation in both groups. Statistically significant differences were found for PSV, MV and EDV when RMCA and LMCA were interrogated before and after sedation. PSV, RI and PI were found to be statistically significantly different when the study was performed on the BA. These results should be taken in account when a transcranial Doppler is performed in dogs sedated with the mentioned protocols and it might suggest some degree of neuroprotection., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Doppler flow indices (DFIs), such as the resistive index (RI) and the pulsatility index (PI), are commonly used to characterize blood flow. Parenchymal infiltration of an organ and administration of sedative and anaesthetic drugs can affect DFIs by altering resistance to blood flow. In this prospective study, the effect on DFIs of two sedative protocols (acepromazine or dexmedetomidine, each combined with butorphanol) and the presence or absence of hepatic and/or splenic disease, was investigated in the splenic arteries of 75 dogs. The RI and PI in splenic arteries of dogs sedated with dexmedetomidine and butorphanol were lower than those of dogs sedated with acepromazine and butorphanol. PI in splenic arteries was higher in animals with hepatosplenic disease than in healthy animals. Receiver Operating Characteristic (ROC) curves suggested that PI measured in canine splenic arteries could be useful in predicting the presence of hepatosplenic disease in the absence of other abdominal disease., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Reasons for Performing Study: Pain management is an important component of foal nursing care, and no objective data currently exist regarding the analgesic efficacy of opioids in foals., Objectives: To evaluate the somatic antinociceptive effects of 2 commonly used doses of intravenous (i.v.) butorphanol in healthy foals. Our hypothesis was that thermal nociceptive threshold would increase following i.v. butorphanol in a dose-dependent manner in both neonatal and older pony foals., Methods: Seven healthy neonatal pony foals (age 1-2 weeks), and 11 healthy older pony foals (age 4-8 weeks). Five foals were used during both age periods. Treatments, which included saline (0.5 ml), butorphanol (0.05 mg/kg bwt) and butorphanol (0.1 mg/kg bwt), were administered i.v. in a randomised crossover design with at least 2 days between treatments. Response variables included thermal nociceptive threshold, skin temperature and behaviour score. Data within each age period were analysed using a 2-way repeated measures ANOVA, followed by a Holm-Sidak multiple comparison procedure if warranted., Results: There was a significant (P<0.05) increase in thermal threshold, relative to Time 0, following butorphanol (0.1 mg/kg bwt) administration in both age groups. No significant time or treatment effects were apparent for skin temperature. Significant time, but not treatment, effects were evident for behaviour score in both age groups., Conclusions: Butorphanol (0.1 mg/kg bwt, but not 0.05 mg/kg bwt) significantly increased thermal nociceptive threshold in neonatal and older foals without apparent adverse behavioural effects., Potential Relevance: Butorphanol shows analgesic potential in foals for management of somatic painful conditions., (© 2012 EVJ Ltd.)

Objective: To quantitatively and qualitatively compare electroretinography (ERG) recordings in awake, sedated, and anesthetized dogs., Animals: Six 6-month-old Beagles., Procedures: A brief ERG protocol for dogs was used. Following 1-minute and subsequent 5-minute dark adaptation, mixed rod-cone responses were recorded bilaterally with a handheld multispecies ERG device with dogs in each of 3 states of consciousness: awake, sedated (dexmedetomidine and butorphanol), and anesthetized (atropine and hydromorphone, followed by propofol and midazolam and anesthetic maintenance with isoflurane). Low- and high-frequency noise levels were quantified via Fourier analysis, and the effect of consciousness state on signal amplitude, implicit time, and noise was analyzed via repeated-measures ANOVA. In addition, 13 veterinary ophthalmologists who were unaware of the dogs' consciousness states subjectively graded the ERG recording quality, and scores for each tracing were compared., Results: ERG amplitudes were highest in awake dogs and lowest in anesthetized dogs. Implicit times were shortest in awake dogs and longest in anesthetized dogs. Differences in b-wave amplitudes and a-wave implicit times were significant. Neither low- nor high-frequency noise levels differed significantly among consciousness states. Furthermore, no significant differences were identified among observers' scores assigned to ERG tracings., Conclusions and Clinical Relevance: Anesthesia and sedation resulted in significant attenuation and delay of ERG responses in dogs. Chemical restraint of dogs had no consistently significant effect on low- or high-frequency noise levels or on observer perception of signal quality.

The purpose of this study was to assess the clinical effects of dexmedetomidine, both alone and combined with pethidine or butorphanol, in cats. A prospective randomized blind study was performed. Thirty cats were randomly assigned to three groups of 10 animals: D: dexmedetomidine (20 μg/kg IM); DP: dexmedetomidine (10 μg/kg IM) and pethidine (2.5 mg/kg IM); DB: dexmedetomidine (10 μg/kg IM) and butorphanol (0.4 mg/kg IM). Quality of sedation, analgesia, muscle relaxation and the possibility of performing some clinical procedures were compared using a multifactorial scale. Sedation, analgesia and muscle relaxation increased progressively over time and did not differ in the three protocols. The three protocols facilitated the completion of several clinical procedures. The clinical variables studied showed a similar behaviour in the three protocols and remained close to the baseline, except for a drop in heart rate in protocol D. In conclusion, dexmedetomidine, either alone or combined with pethidine or butorphanol, offers suitable sedation, analgesia and relaxation to perform various clinical procedures in cats., (© 2012 Blackwell Publishing Ltd.)

Forty free-ranging white rhinoceros (Ceratotherium simum) were anesthetized with etorphine, azaperone, and hyaluronidase in Kruger National Park, South Africa, between February and August 2009. Eighteen rhinoceros received butorphanol in the dart combination, and 22 rhinoceros had butorphanol administered intravenously within 15 min of darting. Body position, blood gas values, heart rate, respiratory rate, and temperature were measured at two time points after darting, approximately 10 min apart (sample 1 mean collection time after darting, 9.4 +/- 2.7 min; sample 2 mean collection time, 18.6 +/- 2.8 min). A significant number of field-captured rhinoceros remained standing at the first sample period when butorphanol was administered in the dart. Higher median values for arterial partial pressure of oxygen (PaO2) in combination with lower arterial partial pressure of carbon dioxide (PaCO2) in standing versus recumbent rhinoceros suggested improved ventilation in this posture (P < 0.05). When the effect of time, body position, and age was controlled, median values for respiratory rate, lactate, and pH were better in rhinoceros that received butorphanol in the dart (P < 0.05). There was also a trend toward higher median values for SO2 and bicarbonate in rhinoceros receiving butorphanol in the dart. Intravenous administration of butorphanol resulted in significantly decreased median PaCO2 and heart rate in recumbent rhinoceros (P < 0.05) without changes in PaO2 between sample periods 1 and 2. However, rhinoceros remained hypoxemic during the short anesthetic procedure despite butorphanol administration. Preliminary results suggest that administration of butorphanol (either in the dart or intravenously) improves some metabolic parameters in free-ranging recumbent white rhinoceros without significantly affecting ventilation. It is hypothesized that this may be due to a lighter state of immobilization. Addition of butorphanol to the dart provides handling and physiologic advantages because the majority of rhinoceros remain standing.

Objective: To record, with a thermal camera, peripheral temperature changes during different sedation protocols and to relate the results to changes in the rectal temperature., Study Design: Randomized crossover part-blinded experimental study., Animals: Eight healthy purpose-bred neutered Beagles (two females and six males) weight 14.5 ± 1.6 kg (mean ± SD) and aged 3-4 years., Methods: Each dog was sedated four times. Treatments were medetomidine 20 μg kg(-1) and butorphanol 0.1 mg kg(-1) (MB) with or without MK-467 500 μg kg(-1) (MK). Both drug combinations were administered IV and IM as separate treatments. A thermal camera (T425, FLIR) with a resolution of 320 by 240 was used for imaging. The dogs were placed in lateral recumbency on an insulated mattress. Digital (DFT) and metatarsal footpad temperatures (MFT) were measured with thermography. Thermograms and rectal temperature (RT) were taken before and at 3, 10, 20, 30, 45 and 60 minutes after treatment., Results: At 60 minutes after drug administration, MFT was higher (p < 0.001) after MB+MK (34.5 ± 1.1 IV, 34.8 ± 0.5 IM) than MB (31.1 ± 2.9 IV, 30.5 ± 3.6 IM), DFT was higher (p < 0.001) after MB+MK (33.6 ± 1.4 IV, 34.0 ± 0.6 IM) than MB (26.7 ± 1.4 IV, 26.7 ± 2.5 IM), and RT was lower (p < 0.001) after MB+MK (36.7 ± 0.8 IV, 36.9 ± 0.3 IM) than MB (37.5 ± 0.3 IV, 37.4 ± 0.4 IM), with both routes. The change from baseline was greater with MB+MK than MB in all variables., Conclusions: Superficial temperature changes can be seen and detected with thermography. MK-467 used with MB resulted in increased superficial temperatures and a decline in rectal temperature compared to MB alone., Clinical Relevance: The sedation protocol may influence core temperature loss, and may also have an effect on thermographic images., (© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Objective: To investigate the safety, sedative and analgesic properties of methadone in combination with acepromazine prior to neutering in cats., Study Design: Controlled clinical, block randomized, prospective, blinded study designed for regulatory purposes., Animals: 24 female and 21 male healthy cats., Methods: Cats received one of three opioids combined with acepromazine (0.05 mg kg(-1) ) intramuscularly (IM) for premedication: Group 1: buprenorphine (0.02 mg kg(-1) ), group 2: methadone (0.5 mg kg(-1) ), group 3 butorphanol (0.4 mg kg(-1) ). Sedation was assessed 30 minutes after premedication using a visual analogue scale (VAS) and simple descriptive scale. Anaesthesia was induced with alfaxalone and maintained with isoflurane in oxygen. Surgical ovariohysterectomy or castration was performed. Pain was assessed using an interactive VAS (IVAS) and mechanical nociceptive threshold (MNT) with a pressure rate onset device. Methadone (0.5 mg kg(-1) IM) and meloxicam (0.2 mg kg(-1) subcutaneously) were provided 6 and 8 hours after premedication respectively, or together as rescue analgesia (IVAS above 50)., Results: Sedation scores, induction agent dose, pain scores at all time points and rescue analgesia were not statistically different between groups. In methadone treated cats there was no significant variation in MNT over time, suggesting a possible anti-hyperalgesic action, whereas in the other two groups lower thresholds were recorded at various time points after surgery compared to baseline. No cats required rescue analgesia after the second dose of methadone. No perioperative adverse effects occurred., Conclusion and Clinical Relevance: Methadone provided comparable sedation and analgesia to both buprenorphine and butorphanol when combined with acepromazine. Differences in analgesic efficacy between opioids might have been undetectable because of the surgical model and surgeon competency. Nevertheless, methadone is an effective analgesic in cats and its administration prior to feline neutering may be advantageous., (© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Anesthetic and cardiorespiratory effects of medetomidine, lidocaine, butorphanol and propofol total intravenous anesthesia (MLBP-TIVA) were evaluated in horses undergoing an experimental surgery. Ten horses were premedicated with an intravenous injection (IV) of medetomidine (5 µg/kg) and butorphanol (20 µg/kg). Anesthesia was induced by administration of 1% propofol (3 mg/kg, IV) at a rate of 1 mg/kg/min (n=5, group-1) or 2% propofol administered at a rate of 6 mg/kg/min (n=5, group-2) following administration of lidocaine (1 mg/kg, IV) and then maintained by infusions of propofol, medetomidine (3.5 µg/kg/hr), lidocaine (3 mg/kg/hr) and butorphanol (24 µg/kg/hr). The mean durations of anesthesia and propofol infusion rate required for maintaining surgical anesthesia were 130 ± 17 min and 0.10 ± 0.01 mg/kg/min in group 1 and 129 ± 14 min and 0.10 ± 0.02 mg/kg/min in group 2. Four horses in group 1 and 2 horses in group 2 paddled following recumbency during induction of anesthesia. The median quality scores for induction (0-4: poor-excellent) and recovery (0-5: unable to stand-excellent) were 3 and 4 for both groups, respectively. Transition to anesthesia (the first 20-min period after induction) was uneventful in group 2, while all horses showed a light plane of anesthesia in group 1. The quality score (0-3: poor-excellent) for the transition to anesthesia in group 2 was significantly higher than in group 1 (median 3 versus 1, P=0.009). Heart rate and arterial blood pressure were maintained within acceptable ranges, but hypercapnia occurred during anesthesia in both groups. In conclusion, MLBP-TIVA may provide clinically useful surgical anesthesia in horses. A rapid induction with propofol may improve the qualities of induction and transition to MLBP-TIVA.

Butorphanol is a narcotic analgesic commonly used in horses. Currently, any detectable concentration of butorphanol in biological samples collected from performance horses is considered a violation. The primary goal of the study reported here was to update the pharmacokinetics of butorphanol following intravenous administration, utilizing a highly sensitive liquid chromatography-mass spectrometry (LC-MS) assay that is currently employed in many drug-testing laboratories. An additional objective was to characterize behavioral and cardiac effects following administration of butorphanol. Ten exercised adult horses received a single intravenous dose of 0.1 mg/kg butorphanol. Blood and urine samples were collected at time 0 and at various times for up to 120 h and analyzed using LC-MS. Mean±SD systemic clearance, steady-state volume of distribution, and terminal elimination half-life were 11.5±2.5 mL/min/kg, 1.4±0.3 L/kg, and 5.9±1.5 h, respectively. Butorphanol plasma concentrations were below the limit of detection (LOD) (0.01 ng/mL) by 48 h post administration. Urine butorphanol concentrations were below the LOD (0.05 ng/mL) of the assay in seven of 10 horses by 120 h post drug administration. Following administration, horses appeared excited as noted by an increase in heart rate and locomotion. Gastrointestinal sounds were markedly decreased for up to 24 h., (© 2012 Blackwell Publishing Ltd.)

We have studied the analgesic activity of a morpholinoethylimidazobenzimidazole derivative (RU-1205) in comparison to butorphanol. It is established that the test compound exhibits a pronounced analgesic activity, which exceeded that ofbutorphanol six times in the hot-plate test and was comparable to the reference drug effect in the tail-flick and acetic acid-induced writhing tests. It is established that the analgesic action of RU-1205 is based on the kappa-opioidergic mechanism.

The rabbit is a good experimental model for brachial plexus surgery. The risks of death during anesthesia were significantly greater in rabbits than cats or dogs. This article presents the protocol of injectable anesthesia for a short surgical procedure, safe for the rabbit patient and convenient for the surgeon.

Objective: To determine the pharmacokinetics and pharmacodynamics of the neurosteroid anaesthetic, alfaxalone, in neonatal foals after a single intravenous (IV) injection of alfaxalone following premedication with butorphanol tartrate., Study Design: Prospective experimental study., Animals: Five clinically healthy Australian Stock Horse foals of mean ± SD age of 12 ± 3 days and weighing 67.3 ± 12.4 kg., Methods: Foals were premedicated with butorphanol (0.05 mg kg(-1) IV) and anaesthesia was induced 10 minutes later by IV injection with alfaxalone 3 mg kg(-1) . Cardiorespiratory variables (pulse rate, respiratory rate, direct arterial blood pressure, arterial blood gases) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and alfaxalone plasma concentrations were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis., Results: The harmonic, mean ± SD plasma elimination half life (t½) for alfaxalone was 22.8 ± 5.2 minutes. The observed mean plasma clearance (Cl(p) ) and volume of distribution (Vd) were 19.9 ± 5.9 mL minute kg(-1) and 0.6 ± 0.2 L kg(-1) , respectively. Overall, the quality of the anaesthetic inductions and recoveries was good and most monitored physiological variables were clinically acceptable in all foals, although some foals became hypoxaemic for a short period following recumbency. The mean durations of anaesthesia from induction to first movement and from induction to standing were 18.7 ± 7 and 37.2 ± 4.7 minutes, respectively., Conclusions: The anaesthetic protocol used provided a predictable and consistent plane of anaesthesia in the five foals studied, with minimal cardiovascular depression. In foals, as in the adult horse, alfaxalone has a short elimination half life., Clinical Relevance: Alfaxalone appears to be an adequate anaesthetic induction agent in foals and the pharmacokinetics suggest that, with continuous infusion, it might be suitable to provide more prolonged anaesthesia. Oxygen supplementation is recommended., (© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)