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Etorphine based immobilization protocols are reported to be effective in pronghorn; however, information on cardiorespiratory effects is limited. The objective of this study was to evaluate the efficacy and cardiopulmonary effects of etorphine, medetomidine, midazolam, and azaperone for immobilization in captive pronghorn. Additionally, the effects of endotracheal intubation and manual ventilation on cardiopulmonary variables were assessed. A combination of 5 mg etorphine, 10 mg medetomidine, 2.5 mg midazolam, and 5 mg azaperone was administered by hand or via dart to 10 pronghorn. Five pronghorn were endotracheally intubated once recumbent and manually ventilated. Oxygen at a flow of 6 L/min was supplemented to all animals. Induction and recovery times were recorded, and during recumbency vital parameters and arterial blood samples were collected. Time to lateral recumbency was 3.8 ± 1.25 min. Marked hypoxemia and hypercapnia was observed in both spontaneously breathing and manually ventilated pronghorn. Hypercapnia improved significantly in manually ventilated pronghorn compared to spontaneously breathing animals. All pronghorn recovered rapidly after reversal with 150 mg naltrexone and 30 mg atipamezole. Administration of etorphine, medetomidine, midazolam, and azaperone resulted in excellent chemical immobilization in pronghorn. Significant hypoxemia and hypercapnia occurred and oxygen supplementation, endotracheal intubation, and manual ventilation is recommended.

Chemical immobilization is commonly used to capture and handle free-ranging elk (Cervus canadensis). Butorphanol-azaperone-medetomidine (BAM) and nalbuphine-medetomidine-azaperone (NalMed-A) are compounded drug combinations that are lower-scheduled in the US than drugs historically used for elk immobilizations. We compared BAM and NalMed-A for immobilization of free-ranging elk using free-darting and Clover trapping. From January 2020 to April 2022, 196 female elk were immobilized in Pennsylvania, USA. We report vital rates, induction and recovery times, and the need for supplemental drugs. We built mixed-effects logistic regression models to describe differences between drug choice based on induction and recovery times, capture method, and individual variation. Several models were competing, including our null model, which suggests that BAM and NalMed-A are comparable based on the parameters we evaluated. Supplemental drug administration was more frequently needed in NalMed-A immobilizations (21.2%) than in BAM immobilizations (9.0%). Overall, we found minor differences between BAM and NalMed-A, both of which appear to be effective for immobilizing elk in both free-darting and Clover trapping scenarios when performing moderately invasive, minimally painful procedures on free-ranging elk., (© Wildlife Disease Association 2024.)

Administration of butorphanol, azaperone, and medetomidine (BAM) for immobilization of black howler monkeys ( Alouatta pigra ) has not been previously reported. In this observational study, 0.02 ml/kg of compounded BAM (butorphanol 27.3 mg/ml, azaperone 9.1 mg/ml, medetomidine 10.9 mg/ml) was administered IM in 10 captive black howler monkeys. Time to immobilization was recorded, an arterial blood gas performed, and at 5-min intervals, HR, RR, oscillometric arterial blood pressure, SPO 2, and rectal temperature were measured. Naltrexone and atipamezole were administered IM at procedure completion and recovery times were recorded. If invasive procedures such as surgery were necessary and additional drugs needed, further data from that individual was removed from data analysis. Final BAM dosages were 0.55 ± 0.12 mg/kg butorphanol, 0.19 ± 0.04 mg/kg azaperone, and 0.22 ± 0.05 mg/kg medetomidine. Nine of 10 monkeys achieved sedation allowing for physical exam, venipuncture, and tuberculin skin testing within 4 ± 2 min. No monkeys reached a plane of immobilization allowing for intubation. Physiologic variables were acceptable for this species. Hypoxemia (SPO 2 < 95%) was observed in three monkeys via pulse oximetry, and normoxemia was observed on arterial blood gas. Recovery was smooth and rapid. Therefore, BAM is a viable option for noninvasive procedures or as a premedication prior to induction of anesthesia in black howler monkeys.

Immobilization kits including butorphanol-azaperone-medetomidine (BAM) and nalbuphine-azaperone-medetomidine can provide effective, safe, and easy-to-use protocols in bears. Nalbuphine-azaperone-medetomidine is not commercially available but may be useful for wildlife agencies because it does not contain controlled substances. This study directly compared BAM to nalbuphine-azaperone-medetomidine immobilization in 10 juvenile healthy black bears (10 mo old; four females, six males) undergoing prerelease examinations after rehabilitation. Bears were immobilized via remote delivery of 1 mL of BAM (n=5) or nalbuphine-azaperone-medetomidine (n=5) intramuscularly in the shoulder during December (randomized, blinded trial). Bears were intubated, monitored with an electrocardiogram, pulse oximeter, capnograph, noninvasive blood pressure cuff, and rectal thermometer, and underwent physical examination, sample collection, morphometrics, and ear-tag placement. Induction, physiologic, and recovery parameters were recorded, including arterial blood gas analysis. The anesthetic agents were antagonized with atipamezole and naltrexone. There were no differences between protocols in induction or recovery times. There were no differences between protocols in heart rate, respiratory rate, temperature, oxygen saturation, end-tidal CO2, mean arterial pressure, or blood gas analysis or any differences between male and female bears in any parameters. Bears were hypertensive and normoxemic with low oxygen saturation via pulse oximeter, but all recovered smoothly and were released within 2 h of recovery. This study supports that nalbuphine-azaperone-medetomidine is clini-cally as safe and effective as BAM in American black bears., (© Wildlife Disease Association 2024.)

Raccoons (Procyon lotor) are frequently handled using chemical immobilization in North America for management and research. In a controlled environment, we compared three drug combinations: ketamine-xylazine (KX), butorphanol-azaperone-medetomidine (BAM), and nalbuphine-medetomidine-azaperone (NalMed-A) for raccoon immobilization. In crossover comparisons, raccoons received a mean of the following: 8.66 mg/kg ketamine and 1.74 mg/kg xylazine (0.104 mL/kg KX); 0.464 mg/kg butorphanol, 0.155 mg/kg azaperone, and 0.185 mg/kg medetomidine (0.017 mL/kg BAM); and 0.800 mg/kg nalbuphine, 0.200 mg/kg azaperone, and 0.200 mg/kg medetomidine (0.020 mL/kg NalMed-A). Induction time was shortest with KX (mean±SE, 10.0±0.7 min) and longest with NalMed-A (13.0±1.3 min). A sampling procedure was completed on 89% (16/18), 72% (13/18), and 89% (16/18) of the raccoons administered KX, BAM, and NalMed-A, respectively. Reasons for incomplete sampling included inadequate immobilization (one KX and one NalMed-A), responsive behaviors (one each with KX, BAM, NalMed-A), or animal safety (four BAM). Mean recovery time for KX was 32.8±7.1 min without antagonizing and 28.6±5.2 min following delivery of an antagonist. Mean recovery time was 6.2±0.8 min for BAM and 5.1±0.5 min for NalMed-A after antagonizing. Only with KX were raccoons observed to recover without use of an antagonist. Supplemental oxygen was provided to 23% (3/13), 72% (13/18), and 71% (12/17) of raccoons immobilized with KX, BAM, and NalMed-A, respectively. Hypoxemia at <80% oxygen saturation occurred in 0% (0/17), 27% (4/15), and 6% (1/16) of the raccoons administered KX, BAM, and NalMed-A, respectively; all raccoons fully recovered from chemical immobilization. All combinations could be used for raccoon immobilization; however, the need for delivery of supplemental oxygen to a majority of raccoons immobilized with BAM and NalMed-A may limit broader use of these agents for certain field studies involving capture, sample, and release of free-ranging animals from a practical standpoint., (© Wildlife Disease Association 2024.)

We evaluated a combination of nalbuphine HCl (40 mg/mL), azaperone tartrate (10 mg/mL), and medetomidine HCl (10 mg/mL), a combination known as NAM or NalMed-A, in 23 ringtails (Bassariscus astutus) during 29 handling events for a radio-collaring study in southern Oregon, US, from August 2020 to March 2022. The combination was delivered to ringtails by hand injection at 0.075 mL NAM per estimated 1 kg body mass. The mean (± standard deviation, SD) dosage calculated post hoc was 3.366 (±0.724) mg/kg nalbuphine, 0.841 (±0.181) mg/kg medetomidine, and 0.841 (±0.181) mg/kg azaperone. All captured ringtails were effectively immobilized with a mean (SD) induction time of 13.24 (±3.57) min. The medetomidine and nalbuphine components were antagonized with a combination of atipamezole and naltrexone HCl with a mean (SD) recovery time of 2.48 (±1.94) min. This combination appeared to be safe and effective for immobilizing ringtails with a low volume dose, smooth antagonism, and rapid recovery. In addition, NAM does not contain any drugs that are US Drug Enforcement scheduled, which makes it useful for immobilization procedures by wildlife professionals in the US., (© Wildlife Disease Association 2023.)

Sable antelope ( Hippotragus niger ), a large, dominant species, often require chemical immobilization for captive management. Despite several recorded protocols, limited objective or subjective data are available to guide chemical immobilization of this species. This study retrospectively compared immobilization drug combinations of carfentanil-xylazine (CX), thiafentanil-xylazine (TX), etorphine-xylazine (EX), carfentanil-acepromazine (CA), and butorphanol-azaperone-medetomidine (BAM) for healthy sable antelope at one institution. Clinically applicable physiologic measures, subjective ratings, and timing of anesthetic milestones of 161 events for 107 individuals revealed the following statistically significant findings ( P < 0.05). Induction ratings were best for TX, highest degree of muscle relaxation occurred with BAM and TX, and anesthetic ratings were best for TX and EX. Time to recovery was longest and complications 2.56 times more likely with CX. Time to recumbency was shortest in TX. Heart rate was highest in CA and lowest in BAM. For immobilization procedures, this study suggests TX would be the preferred combination for H. niger . However, all drug combinations evaluated can be used successfully to immobilize H. niger, and certain combinations may be situationally preferred based on desired muscle relaxation, expected induction or recovery times, or anticipated procedure length.

Chemical immobilization is widely used by wildlife and veterinary professionals for the safe handling of animals. A combination of nalbuphine (40 mg/mL), azaperone (10 mg/mL), and medetomidine (10 mg/mL), known as NAM, is a low-volume combination with field immobilization practicality and fewer regulations restricting its use in the US than some other drug combinations. We evaluated the safety and effectiveness of NAM as an immobilizing agent for raccoons (Procyon lotor). From May 2021 to February 2022, 16 adult raccoons were captured in cage traps and immobilized with 0.3 mL NAM intramuscularly (12 mg nalbuphine, 3 mg medetomidine, and 3 mg azaperone, regardless of body weight). After administration, time to sedation was measured; body temperature, heart rate, respiratory rate, and oxygen saturation were monitored and recorded every 5 min for 20 min. Each raccoon was weighed; the dose administered was calculated (range 2.2-4.1 mg/kg, mean 3 mg/kg). Mean induction time was 6 min (4-17 min); time to recovery following administration of 15 mg atipamezole, 7.5 mg naltrexone for reversal, was 10 min (6-18 min). Heart rate, oxygen saturation, and respiration rate remained steady during immobilization. Rectal temperature steadily declined. Overall, NAM appeared to be a practical option for raccoon immobilization, providing rapid induction and reversal as well as adequate sedation for short-term handling and minimally invasive sampling., (© Wildlife Disease Association 2023.)

A combination of tiletamine-zolazepam, medetomidine, and azaperone was used to immobilize captive Chacoan peccaries (Catagonus wagneri) for health assessments and biological sample collection at the Centro Chaqueño para la Conservación e Investigación (CCCI) in the Paraguayan Chaco during July in 2017 and 2018. In total, 83 peccaries kept in 0.25-1.50 hectare enclosures were immobilized via dart-administered anesthetic. Mean animal weight was 33.89±3.74 kg (standard deviation; n=77). The mean intramuscular (IM) anesthetic drug and dosages were 0.03±0.00 mg/kg of medetomidine, 0.91±0.10 mg/kg of Zoletil 50 (tiletamine-zolazepam), and 0.30±0.03 mg/kg azaperone. The mean time to recumbency after darting was 6.07±2.65 min. The mean time to reach the anesthetic plane postdarting was 10.00±2.00 min. Muscle relaxation was adequate to allow minor veterinary procedures. A mean dosage of 0.15±0.02 mg/kg of atipamezole was given IM to reverse the medetomidine. Recoveries were smooth and animals were standing by 59.17±30.18 min postreversal. Full recovery and release back to enclosures occurred 90±30 min postreversal. A single dose of this drug combination provided adequate anesthesia for 88% of adult Chacoan peccaries; 12% needed a supplemental dose of tiletamine-zolazepam because of failure to receive the full dose from the anesthetic dart. Sex and age did not impact the dosage required to achieve immobilization. Confinement during recovery from anesthesia is required with this protocol. Aside from mild hypoxemia, no adverse effects from anesthesia were observed. However, oxygen supplementation as a part of this protocol is recommended to support circulatory and respiratory capacity., (© Wildlife Disease Association 2023.)

We chemically immobilized a free-ranging moose subspecies, Shiras moose (Alces alces shirasi), using a combination of butorphanol (27.3 mg/mL), azaperone (9.1 mg/mL), and medetomidine (10.9 mg/mL). Ground and helicopter darting with fixed doses of 2 mL and 3 mL, respectively, safely immobilized 13 individuals in Wyoming, USA., (© Wildlife Disease Association 2023.)

Objective: To determine the pharmacokinetics of a single bolus of intravenous (IV) propofol after intramuscular administration of etorphine, butorphanol, medetomidine, and azaperone in 5 southern white rhinoceros to facilitate reproductive evaluations. A specific consideration was whether propofol would facilitate timely orotracheal intubation., Animals: 5 adult, female, zoo-maintained southern white rhinoceros., Procedures: Rhinoceros were administered etorphine (0.002 mg/kg), butorphanol (0.02 to 0.026 mg/kg), medetomidine (0.023 to 0.025 mg/kg), and azaperone (0.014 to 0.017 mg/kg) intramuscularly (IM) prior to an IV dose of propofol (0.5 mg/kg). Physiologic parameters (heart rate, blood pressure, respiratory rate, and capnography), timed parameters (eg, time to initial effects and intubation), and quality of induction and intubation were recorded following drug administration. Venous blood was collected for analysis of plasma propofol concentrations using liquid chromatography-tandem mass spectrometry at various time points after propofol administration., Results: All animals were approachable following IM drug administration, and orotracheal intubation was achieved at 9.8 ± 2.0 minutes (mean ±SD) following propofol administration. The mean clearance for propofol was 14.2 ± 7.7 ml/min/kg, the mean terminal half-life was 82.4 ± 74.4 minutes, and the maximum concentration occurred at 2.8 ± 2.9 minutes. Two of 5 rhinoceros experienced apnea after propofol administration. Initial hypertension, which improved without intervention, was observed., Clinical Relevance: This study provides pharmacokinetic data and insight into the effects of propofol in rhinoceros anesthetized using etorphine, butorphanol, medetomidine, and azaperone. While apnea was observed in 2 rhinoceros, propofol administration allowed for rapid control of the airway and facilitated oxygen administration and ventilatory support.

Chemical immobilization of wildlife, required for many biological studies and management events, often induces hypoxemia and respiratory depression. Laryngeal mask airways (LMAs) have shown promise as an efficient method of airway protection during anesthesia. Nineteen wild bighorn sheep ( Ovis canadensis ) lambs were immobilized using an IM combination of medetomidine (0.16 ± 0.062 mg/kg), azaperone (0.20 ± 0.058 mg/kg), and alfaxalone (0.54 ± 0.21 mg/kg) via remote injection. Upon recumbency, arterial blood gas parameters, minute ventilation (V E ), tidal volume (V T ), and respiratory rate were measured before and after LMA placement. The V E and V T were measured via respirometer. Time to LMA placement, cuff pressure, cuff volume, and ease of placement were measured. Medetomidine was reversed with IM atipamezole at five times the medetomidine dose upon completion of procedures. Pre- and post-LMA measurements were compared using a t test or a Wilcoxon signed-rank test based on normality of the data. The LMA provided a patent airway in all lambs with a significant ( P < 0.0001) increase in VE (mean [95% CI]; pre-LMA: V E = 17.3 [16.2-18.5] L/min, post-LMA: V E = 19.8 [18.6-21.0] L/min) but did not have a significant impact on partial pressure of oxygen (PaO 2 ; pre-LMA: corrected PaO 2 = 45.2 [41.2-49.2] mm Hg, post-LMA: corrected PaO 2 = 47.5 [43.3-51.7] mm Hg; P = 0.19) or partial pressure of carbon dioxide (PaCO 2 ; pre-LMA: PaCO 2 = 50.4 [46.6-53.2] mm Hg, post-LMA: PaCO 2 = 51.6 [48.8-55.7] mm Hg; P = 0.035) following placement. This study demonstrated that the LMA is a viable option for airway protection in wild bighorn sheep.

We evaluated the safety and efficacy of nalbuphine (40 mg/mL), plus medetomidine (10 mg/mL), plus azaperone (10 mg/mL) under the premixed label NalMed-A. From January to March 2020, 10 aoudad (Ammotragus lervia) were immobilized via dart-gun for seven separate sampling periods for a total of 45 recorded individual immobilization events. Induction and reversal times with NalMed-A were 5.53±2.61 min and (following atipamezole administration) 5.08±2.43 min while previous studies with alpha-2 agonist-ketamine combinations gave median and average induction times of 4.6 min and 11.2 min using medetomidine-ketamine and xylazine-ketamine, respectively. Overall, NalMed-A adequately immobilized aoudad, with 13% incidence of hyperthermia and 2.22% mortality when delivered via dart., (© Wildlife Disease Association 2022.)

Abstract: The study compared immobilisation of blesbok ( Damaliscus pygargus phillipsi ) with etorphine and azaperone vs etorphine and midazolam. Twelve female blesbok, weighing 59.4 ± 2.8 kg, were used. Each animal randomly received Treatment 1 (T1) (etorphine, 0.07 ± 0.003 mg/kg + azaperone, 0.36 ± 0.02 mg/kg) and Treatment 2 (T2) (etorphine, 0.07 ± 0.003 mg/kg + midazolam, 0.20 ± 0.01 mg/kg) with a one-week washout period between treatments. Induction times were recorded followed by physiological monitoring for 45 minutes of immobilisation. Immobilisation was reversed with naltrexone (20 mg per mg etorphine). Recovery times were also recorded. Induction, immobilisation and recovery were scored with subjective measures. Inductions and recoveries did not differ between combinations, but the quality of immobilisation was significantly better with T1. Rectal temperature and blood pressure were significantly lower during T1. Both treatments resulted in severe hypoxaemia and impaired gas exchange, although overall hypoxaemia was more pronounced for T1. Animals treated with T2, however, exhibited a deterioration in respiration as the monitoring period progressed, possibly as a result of impaired ventilatory muscle function due to the effects of midazolam. Both combinations are suitable for adequate immobilisation of blesbok and should be selected based on the specific capture situation. Supplementation with oxygen is highly recommended., (Copyright© Authors.)

Objective: To compare ketamine-butorphanol-azaperone-medetomidine (KBAM) to detomidine-etorphine-acepromazine (DEA) for field anesthesia in captive Przewalski horses (Equus przewalskii)., Animals: 10 adult Przewalski horses., Procedures: A prospective randomized crossover trial was conducted. Each horse was immobilized once with KBAM (200 mg ketamine, 109.2 mg butorphanol, 36.4 mg azaperone, and 43.6 mg medetomidine) and once with DEA (40 mg detomidine premedication, followed 20 minutes later by 3.9 to 4.4 mg etorphine and 16 to 18 mg acepromazine). Both protocols were administered by IM remote dart injection with a washout period of 6 months between treatments. Selected cardiorespiratory variables and quality of anesthesia were recorded. Antagonists were administered IM (KBAM, 215 mg atipamezole and 50 mg naltrexone; DEA, 4 mg RX821002 and 100 mg naltrexone)., Results: All horses were anesthetized and recovered uneventfully. Inductions (DEA, 6.8 min; KBAM, 11.6 min; P = 0.04) and recoveries (DEA, 3.2 min; KBAM, 19.6 min; P < 0.01) were faster with DEA compared with KBAM. Quality scores for induction and recovery did not differ between protocols, but maintenance quality was poorer for DEA (P < 0.01). Clinical concerns during DEA immobilizations included apnea, severe hypoxemia (arterial partial pressure of oxygen < 60 mm Hg), muscle rigidity, and tremors. Horses treated with KBAM were moderately hypoxemic, but arterial partial pressures of oxygen were higher compared with DEA (P < 0.01)., Clinical Relevance: Captive Przewalski horses are effectively immobilized with KBAM, and this protocol results in superior muscle relaxation and less marked hypoxemia during the maintenance phase, but slower inductions and recoveries, compared with DEA.

Objective: To determine the time course and certain cardiopulmonary effects of trunk-breathing elephants immobilized with thiafentanil-azaperone., Study Design: Prospective descriptive study., Animals: A convenience sample of 10 free-ranging African elephant bulls (estimated weight range: 3000-6000 kg)., Methods: Elephants were immobilized using thiafentanil (15-18 mg) and azaperone (75-90 mg) administered by dart. Once recumbent, the respiratory rate, minute ventilation (V˙e), end-tidal carbon dioxide (Pe'CO 2 ), arterial blood pressure and heart rate were recorded immediately after instrumentation and at 5 minute intervals until 20 minutes. Arterial blood gases were analysed at the time of initial instrumentation and at 20 minutes. On completion of data collection, thiafentanil was antagonized using naltrexone (10 mg mg -1 thiafentanil; administered intravenously). A stopwatch was used to record time to recumbency (dart placement to recumbency) and time to recovery (administration of antagonist to standing). Data were compared using a one-way anova. Data are presented as mean ± standard deviation., Results: All elephants were successfully immobilized, and there were no significant changes in cardiopulmonary variables over the monitoring period. Average time to recumbency was 12.5 (± 3.9) minutes. The measured V˙e was 103 (± 30) L minute -1 . The average heart and respiratory rates over the 20 minute immobilization were steady at 49 (± 6) beats minute -1 and 5 (± 1) breaths minute -1 , respectively. The mean arterial blood pressure was 153 (± 31) mmHg. The elephants were acidaemic (pH: 7.18 ± 0.06), mildly hypoxaemic (PaO 2 : 68 ± 15 mmHg; 9.1 ± 2.0 kPa) and hypercapnic (PaCO 2 : 52 ± 7 mmHg; 6.9 ± 0.9 kPa). Average time to recovery was 2.2 ± 0.5 minutes., Conclusion and Clinical Relevance: African elephant bulls can be successfully immobilized using thiafentanil-azaperone. Recumbency was rapid, the cardiopulmonary variables were stable over time, and recovery was rapid and complete. Mild hypoxaemia and hypercapnia were evident., (Copyright © 2022 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Background: Butorphanol-azaperone-medetomidine (BAM™) has not been evaluated in horses., Objectives: The objective of this study was to evaluate BAM™ for chemical restraint of feral horses., Study Design: Retrospective and prospective descriptive studies., Methods: Data were collected retrospectively from medical records of 28 feral horses immobilised with BAM™ over a 6-year period. Prospectively, 0.0125 mL/kg bwt of BAM™ (butorphanol 27.3 mg/mL, azaperone 9.1 mg/mL and medetomidine 10.9 mg/mL) intramuscularly (im) was administered to eight stallions via dart, and once recumbent, 1.0 mg/kg bwt ketamine was given intravenously (iv). Induction and recovery time and quality via a standardised rubric (1 = very poor; 5 = excellent) and visual analogue scale (VAS), need for additional darts, weight tape measurement and serial physiological parameters were recorded. Serial arterial blood gas analysis was performed during recumbency. Following castration, horses were given 0.1 mg/kg bwt atipamezole (25% iv and 75% im) and allowed to recover unaided., Results: Retrospectively, 28 horses were successfully immobilised with BAM™ without a major complication. Prospectively, eight horses were given a median (range) actual BAM TM dose of 0.0143 (0.0127-0.0510) mL/kg bwt. Three of eight horses needed 1, 2 or 5 additional darts. Median (range) time to recumbency was 11 (2-44) minutes. Median (range) induction (n = 4) and recovery (n = 6) scores via rubric and VAS were 5 (4-5) and 5 (5-5) and 92 (86-93) and 98 (92-99) cm, respectively. Four of seven horses were hypoxaemic at ≥1 time point with otherwise acceptable physiological parameters. Following atipamezole, median (range) time to sternal recumbency and standing was 12 (2-18) and 17 (11-52) minutes, respectively (n = 6)., Main Limitations: The sample size was small. Data could not be collected before darting or after recovery. Some data were missing from retrospective analysis., Conclusions: Intramuscular BAM™ with iv ketamine provided chemical restraint suitable for field castration of feral horses with no mortality. Hypoxaemia occurred in the majority of horses., (© 2021 EVJ Ltd.)

We describe induction time in six white rhinoceros (Ceratotherium simum) when they received etorphine intramuscularly (IM) or etorphine plus azaperone IM. The median induction time was reduced from 8.9 min for etorphine alone to 6.25 min with azaperone; however, there was no difference in immobilization quality between treatments., (© Wildlife Disease Association 2022.)

Netgun capture is a commonly used capture method for mule deer (Odocoileus hemionus) in North America. Mortalities during netgun captures are generally low, and most often caused by direct trauma and occasionally fatal capture myopathy. Capture is a stressful event for a wild animal, and subclinical capture myopathy is difficult to measure. The use of tranquilizers during netgun capture is not widespread. We compared physiologic variables from 250 netgun-captured deer (57 males and 193 females) that did or did not receive midazolam and azaperone (mean, 0.14 mg/kg; SD, 0.02 mg/kg; range, 0.08-0.21 mg/kg) at time of capture and before transporting to a processing location, with the goal of evaluating whether drug administration would improve or worsen the physiologic state of the animal. Deer were captured in association with management activities between December 2018 and March 2020, with 132 deer receiving midazolam and azaperone at time of capture. Variables recorded included chase times, time from capture to arrival at the processing location, time from capture to release, serial rectal temperatures, heart rates, respiratory rates, body condition, age, sex, O2 administration, creatine kinase, aspartate aminotransferase, packed cell volume, red blood cell concentration, and hemoglobin, as well as serial venous pH, pCO2, HCO3-, and base excess. All animals were collared with GPS tracking devices and monitored after release. There was no difference in survival after capture between deer that did or did not receive midazolam and azaperone. All animals experienced severe metabolic lactic acidosis, which generally worsened with increasing chase time, highlighting the critical importance of limiting chase times during captures. Drug administration did not influence the degree of metabolic acidosis; however, it appeared to have a favorable effect on several stress-related indices, including rectal temperature, heart rate, respiratory rate, and packed cell volume., (© Wildlife Disease Association 2022.)

Chemical immobilisation is essential for veterinarians to perform medical procedures in wild African ungulates. Potent opioids combined with neuroleptic drugs are most often used for this purpose. The present study aimed at comparing the quality of immobilisation and effects on physiological variables between a high (high etorphine-azaperone [HE]: 0.09 mg kg-1) and low etorphine dose (low etorphine-azaperone [LE]: 0.05 mg kg-1), both combined with azaperone (0.35 mg kg-1), in 12 adult female boma-acclimatised blesbok. It was hypothesised that a reduction in etorphine's dose in combination with azaperone would result in less cardiorespiratory impairment but likely worsen the quality of immobilisation. Both treatments resulted in rapid induction and recovery times. Overall inter-treatment differences occurred in pulse rate (HE and LE: 52 ± 15 and 44 ± 11 beats minute-1, p 0.0001), respiratory rate (HE and LE: 15 ± 4 and 17 ± 4 breaths minute-1, p 0.006), partial pressure of exhaled carbon dioxide (HE and LE: 62.0 ± 5.0 and 60.0 ± 5.6 millimetre of mercury [mmHg], p 0.028) and arterial carbon dioxide (HE and LE: 58.0 ± 4.5 and 55.0 ± 3.9 mmHg, p 0.002). Both HE and LE led to bradycardia, hypertension and marked hypoxia to a similar extent. Furthermore, quality of induction, immobilisation and recovery were similar in both treatments. The role of azaperone in the development of cardiorespiratory compromise and gas exchange impairment that occurred when these combinations were used is still unclear. Further studies are recommended to elucidate drug- and dose-specific physiological effects in immobilised antelope.

Etorphine-azaperone is the most commonly used drug combination for chemical immobilisation of free-ranging white rhinoceroses, but causes several profound physiological disturbances, including muscle tremors. The addition of benzodiazepine sedatives, such as midazolam, has been proposed to reduce the muscular rigidity and tremors in immobilised rhinoceroses. Twenty-three free-ranging, sub-adult white rhinoceros bulls were darted and captured using a combination of etorphine plus either azaperone or midazolam. Skeletal muscle tremors were visually evaluated and scored by an experienced veterinarian, and tremor scores and distance run were compared between groups using the Wilcoxon rank sum test. No statistical differences were observed in tremor scores (p = 0.435) or distance run (p = 0.711) between the two groups, and no correlation between these variables was detected (r = -0.628; p = 0.807). Etorphine-midazolam was as effective as etorphine-azaperone at immobilising rhinoceroses, with animals running similar distances. Although the addition of midazolam to the etorphine did not reduce tremor scores compared to azaperone, it might have other beneficial immobilising effects in rhinoceroses, and further investigation is necessary to elucidate possible methods of reducing muscle tremoring during chemical immobilisation of rhinoceroses.

Fifty-three free-ranging moose ( Alces americanus ) cows were darted from a helicopter with 3-4 ml of a premix combination of butorphanol (27.3 mg/ml), azaperone (9.1 mg/ml), and medetomidine (10.9 mg/ml; BAM), equivalent to estimated dosages of: butorphanol 0.26 ± 0.08 (mean ± SD) mg/kg, azaperone 0.09 ± 0.03 mg/kg, and medetomidine 0.11 ± 0.03 mg/kg. After a mean chase time (from sighting to darting) of 6.1 ± 5.5 min, the mean induction time (from darting to recumbency) was 8.3 ± 2.6 min. This combination provided a safe and reliable sedation for minor procedures that lasted 30-60 min. Heart rate (50.4 ± 7.0 beats/min), respiratory rate (21.3 ± 11.1 breaths/minute), ETCO 2 via nasal canula (43.2 ± 7.0 mmHg), and rectal temperature (38.5°C ± 0.7°C) mostly remained at expected values for wild cervid and bovid species anesthetized with this drug combination. SpO 2 (90.0% ± 3.7%) was suggestive of moderate hypoxemia despite intranasal oxygen supplementation (1 L per 100 kg/min). The recovery time to standing was 6.7 ± 3.8 min after reversal with IM naltrexone (3 mg/mg butorphanol) and atipamezole (5 mg/mg medetomidine). Despite a larger volume to inject, this protocol offers an alternative to highly potent opioids, and should be considered for practical or staff safety reasons. On the basis of the results of this study, the use of 4 ml of BAM is considered a safe and effective protocol for immobilization of cow moose under comparable settings.

Objective: To assess the efficacy of butorphanol-azaperone-medetomidine (BAM) and butorphanol-midazolam-medetomidine (BMM) protocols for immobilization of wild common palm civets (Paradoxurus musangus) with subsequent antagonization with atipamezole., Study Design: Prospective, randomized, blinded clinical trial., Animals: A total of 40 adult wild common palm civets, 24 female and 16 male, weighing 1.5-3.4 kg., Methods: The civets were randomly assigned for anesthesia with butorphanol, azaperone and medetomidine (0.6, 0.6 and 0.2 mg kg -1 , respectively; group BAM) or with butorphanol, midazolam and medetomidine (0.3, 0.4 and 0.1 mg kg -1 , respectively; group BMM) intramuscularly (IM) in a squeeze cage. When adequately relaxed, the trachea was intubated for oxygen administration. Physiological variables were recorded every 5 minutes after intubation. Following morphometric measurements, sampling, microchipping and parasite treatment, medetomidine was reversed with atipamezole at 1.0 or 0.5 mg kg -1 IM to groups BAM and BMM, respectively. Physiological variables and times to reach the different stages of anesthesia were compared between groups., Results: Onset time of sedation and recumbency was similar in both groups; time to achieve complete relaxation and tracheal intubation was longer in group BAM. Supplementation with isoflurane was required to enable intubation in five civets in group BAM and one civet in group BMM. All civets in group BAM required topical lidocaine to facilitate intubation. End-tidal carbon dioxide partial pressure was lower in group BAM, but heart rate, respiratory rate, rectal temperature, peripheral hemoglobin oxygen saturation and mean arterial blood pressure were not different. All civets in both groups recovered well following administration of atipamezole., Conclusions and Clinical Relevance: Both BAM and BMM combinations were effective for immobilizing wild common palm civets. The BMM combination had the advantage of producing complete relaxation that allowed intubation more rapidly., (Copyright © 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Alfaxalone has been successfully used intramuscularly (im) combined with medetomidine and azaperone for immobilization of small ungulates. An experimental 40 mg/ml alfaxalone solution (RD0387) was recently formulated for reduced injection volume. The objective of this study was to assess the efficacy and cardiopulmonary effects of high-concentration alfaxalone combined with medetomidine and azaperone for the intramuscular immobilization of captive Rocky Mountain elk ( Cervus elaphus nelsoni ). Seven adult female elk were used in a crossover design in which they were administered alfaxalone 1 mg/kg, medetomidine 0.05 mg/kg, and azaperone 0.1 mg/kg or alfaxalone 0.5 mg/kg, medetomidine 0.1 mg/kg, and azaperone 0.1 mg/kg im approximately 3 wk apart. Drugs were delivered to each elk in a chute by hand injection. Once recumbent, elk were placed in sternal recumbency for a period of 30 min, during which time level of sedation, response to minor procedures, heart rate, respiratory rate, rectal temperature, oxygen saturation, and direct arterial blood pressures were recorded every 5 min. Arterial blood gases were performed every 15 min. At 30 min, elk were administered atipamezole 0.25 or 0.5 mg/kg im and recovery quality and times were recorded. Statistical comparisons were made by t test, Wilcoxon signed rank test, and repeated measures analysis (significance level P < 0.05). Both drug combinations provided effective immobilization for 30 min, with induction and recovery time and quality similar to other medetomidine-based combinations used in elk. Cardiopulmonary effects included bradycardia, hypertension, and hypoxemia that resolved with oxygen supplementation. The average injection volume in the low-dose alfaxalone combination was approximately 5 ml. These combinations provided deep sedation and the ability to perform minor procedures in captive elk, with acceptable cardiopulmonary parameters as long as supplemental oxygen was provided.

The tranquilizer combination of butorphanol, azaperone, and medetomidine (BAM) has shown good efficacy for immobilization of wildlife, including black bears (Ursus americanus). BAM is antagonized with a combination of naltrexone and atipamezole. We immobilized 19 adult captive wild caught black bears and, except for three bears that were euthanized immediately, bears were recovered with naltrexone and atipamezole. Tissue residues (≥0.01 ppm) for the tranquilizers butorphanol, azaperone, and medetomidine were detected in liver and muscle of all three bears euthanized on day 0 postinjection (PI). Azaperone was not detected after 1 d PI. Residue for medetomidine was detected in two bears: in the liver 3 d PI and in the kidney 6 d PI. Butorphanol was reported in three bears: in fat 5 d PI, in kidney 6 d PI, and, surprisingly, in kidney, muscle, and fat 7 d PI. No tissue residues were detected in the three bears euthanized at 8 d PI. Tissue residues for the antagonists, naltrexone and atipamezole, were detected in bears euthanized 2 and 6 d PI, but not in tissues from animals euthanized at 7 or 8 d PI., (© Wildlife Disease Association 2020.)

Objective: To evaluate the immobilization quality and cardiopulmonary effects of etorphine alone compared with etorphine-azaperone in blesbok (Damaliscus pygargus phillipsi)., Study Design: Blinded, randomized, crossover design., Animals: A total of 12 boma-habituated female blesbok weighing [mean ± standard deviation (SD)] 57.5 ± 2.5 kg., Methods: Each animal was administered etorphine (0.09 mg kg -1 ) or etorphine-azaperone (0.09 mg kg -1 ; 0.35 mg kg -1 ) intramuscularly with 1-week intertreatment washout period. Time to first sign of altered state of consciousness and immobilization time were recorded. Physiological variables were recorded, arterial blood samples were taken during a 40-minute immobilization period, and naltrexone (mean ± SD: 1.83 ± 0.06 mg kg -1 ) was intravenously administered. Recovery times were documented, and induction, immobilization and recovery were subjectively scored. Statistical analyses were performed; p < 0.05 was significant., Results: No difference was observed in time to first sign, immobilization time and recovery times between treatments. Time to head up was longer with etorphine-azaperone (0.5 ± 0.2 versus 0.4 ± 0.2 minutes; p = 0.015). Etorphine caused higher arterial blood pressures (mean: 131 ± 17 versus 110 ± 11 mmHg, p < 0.0001), pH, rectal temperature and arterial oxygen partial pressure (59.2 ± 7.7 versus 42.2 ± 9.8 mmHg), but lower heart (p = 0.002) and respiratory rates (p = 0.01). Etorphine-azaperone combination led to greater impairment of ventilatory function, with higher end-tidal carbon dioxide (p < 0.0001) and arterial partial pressure of carbon dioxide (58.0 ± 4.5 versus 48.1 ± 5.1 mmHg). Immobilization quality was greater with etorphine-azaperone than with etorphine alone (median scores: 4 versus 3; p < 0.0001)., Conclusions and Clinical Relevance: Both treatments provided satisfactory immobilization of blesbok; however, in addition to a deeper level of immobilization, etorphine-azaperone caused greater ventilatory impairment. Oxygen supplementation is recommended with both treatments., (Copyright © 2020 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Five free-ranging male (subadults, n = 3; adults, n = 2) plains zebras ( Equus quagga ) were immobilized using a combination of etorphine (0.017 mg/kg), medetomidine (0.017 mg/kg), and azaperone (0.24 mg/kg) by means of a blank cartridge-fired projector. Time to recumbency was recorded and a descriptive score used to assess the quality of immobilization, manipulation, maintenance, and recovery. Physiological parameters were recorded at 5-min intervals for 20 min. At the end of the procedure, naltrexone (0.23 mg/kg) was administered intramuscularly and time to standing documented. The combination evaluated in this study allowed for successful immobilization and safe recovery of all animals, including during the subsequent 15 days. Despite the good outcome in this pilot study, as a result of the periodic apneic events and hypercapnia documented in the zebras, the authors suggest that physiological parameters be thoroughly monitored when using this protocol. Further studies are needed to improve upon chemical immobilization protocols in free-ranging plains zebras.

The care and management of deer in captivity is challenging, especially in the case of red brocket deer (Mazama americana), whose routine management using physical restraint is difficult. Our study evaluated the effects of azaperone and xylazine combination for immobilizing red brocket deer and allow for the standard capture and handling protocols (e.g., biological material, horn cutting, and trimming) to be conducted safely. Six adult, captive, red brocket deer received an intramuscular injection of either 1 mg/kg azaperone and 0.5 mg/kg xylazine (AX0.5) or 1 mg/kg azaperone and 1 mg/kg xylazine (AX1.0). Sedation latency, sternal recumbency, safe handling, and quality of the sedation were evaluated to provide an overview of how the immobilizing drugs affected managing the species in captivity. Additionally, heart rate, respiratory rate, mean arterial pressure, rectal temperature, pH, PaO2, PaCO2, SaO2, HCO3-, BE, Na+, K+ and serum lactate were also measured. The latency period of the animals in the AX0.5 group was greater than that of the animals in the AX1.0 group (7 ± 6.6 min vs. 5 ± 2.0 min), as was the time for them to assume sternal recumbency (12 ± 9.7 min vs. 6 ± 3.1 min). However, the time after the initial dose at which the animals could safely be handled (14 ± 4.5 min vs. 12 ± 5.2 min), and the time until the end of the safe handling period (75 ± 12.3 min vs. 85 ± 6.8 min) were similar for both groups. Animals in both groups showed physiological stability during all evaluations, but hypoxemia was observed in one animal in each group. We conclude that both drug combinations are safe and effective at sedating red brocket deer in captivity and suggest that the procedure be performed with oxygen supplementation to reduce the potential for hypoxia., Competing Interests: The authors have declared that no competing interests exist.

Objective: To compare immobilization efficacy of a nonpotent opioid drug combination, ketamine-butorphanol-medetomidine (KBM) to the preferred etorphine-azaperone (EA) combination in zebras., Study Design: Randomized crossover trial., Animals: A group of ten adult zebra (six females and four male)., Methods: KBM and EA were administered once to the zebras in random order by dart, 3 weeks apart. Once a zebra was recumbent and instrumented, physiological parameters were measured and recorded at 5-minute intervals until 20 minutes. Antagonist drugs were administered at 25 minutes. KBM was antagonised using atipamezole (7.5 mg mg -1 medetomidine dose) and naltrexone (2 mg mg -1 butorphanol dose). EA was antagonized using naltrexone (20 mg mg -1 etorphine dose). Induction and recovery (following antagonist administration) times were recorded. Physiological parameters, including invasive blood pressure and blood gas analysis, were compared between combinations using a general linear mixed model. Data are reported as mean ± standard deviation or median (interquartile range)., Results: The doses of KBM and EA administered were 3.30 ± 0.18, 0.40 ± 0.02 and 0.16 ± 0.01 mg kg -1 ; and 0.02 ± 0.001 and 0.20 ± 0.01 mg kg -1 , respectively. KBM and EA induction times were 420 (282-564) and 240 (204-294) seconds, respectively (p = 0.03). Zebras remained recumbent throughout the study procedures. Systolic blood pressure (226 ± 42 and 167 ± 42 mmHg) and oxygen partial pressure (64 ± 12 and 47 ± 13 mmHg) were higher for KBM compared to EA (p < 0.01). Recovery time, after administering antagonists, was 92 (34-1337) and 26 (22-32) seconds for KBM and EA, respectively (p = 0.03)., Conclusions and Clinical Relevance: Compared to EA, KBM also immobilized zebras effectively. Systemic hypertension and moderate hypoxaemia are clinical concerns of KBM and severe hypoxaemia is a concern of EA. This occurrence of hypoxaemia highlights the importance of oxygen administration during immobilization., (Copyright © 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Thirty-two American beavers ( Castor canadensis ) were immobilized with a mixture of nalbuphine, medetomidine, and azaperone (NalMedA) for tail transmitter placement and health assessments prior to translocation. Inductions and reversals were very smooth, but regardless of the dose administered, which ranged from 0.02 to 0.06 mL/kg, many beavers reacted to mild stimuli such as being lifted out of the cage, drawing blood from the tail, expressing anal glands for sex determination, and turning on isoflurane to deepen anesthesia before placement of tail transmitters. On a scale from 1 to 5, a sedation score of 4 was achieved in 8/32 beavers and a sedation score of 5 in 1/32 of beavers given a mean (SD) dosage of 0.04 (0.01) mL/kg NalMedA, which equated to a mean of 1.09 (0.21) mg/kg nalbuphine, 0.43 (0.09) mg/kg medetomidine, and 0.36 (0.07) mg/kg azaperone. All other animals achieved lower sedation scores. Supplementary isoflurane was needed to deepen anesthesia before tail transmitter placement. Although Nal-MedA appeared to be safe for use in American beavers, the level of sedation achieved was quite variable. Supplementary oxygen is recommended to reduce hypoxemia.

Maximizing animal wellbeing by minimizing drug-related side effects is a key consideration when choosing pharmaceutical agents for chemical restraint in nonhuman primates. One drug combination that may promote this ideology is butorphanol (27.3 mg/mL), azaperone (9.1 mg/mL), and medetomidine (10.9 mg/mL; BAM). Based on results from a pilot study, 2 doses of BAM (16 and 24 μL/kg IM) were compared in healthy, 3-y-old rhesus macaques. Physiologic parameters and anesthetic quality were assessed and recorded every 5 min. Experimental endpoints were established for hypoxemia (85% or less peripheral oxygen saturation with oxygen supplementation), pulse rate (80 bpm or less for 2 consecutive readings), mean arterial pressure (MAP; 50 mm Hg or less), and hypothermia (97 °F or less); if any endpoint was achieved, medetomidine was reversed by using atipamezole (0.22 mg/kg IM). Both BAM doses resulted in immobilization of all animals with no clinically significant differences between groups. All animals initially exhibited hypoxemia that resolved with oxygen supplementation. Regardless of dose, most macaques (71%) reached established experimental endpoints for bradycardia (62 to 80 bpm) or hypotension (44 to 50 mm Hg MAP). Given the results of this study, our recommendation regarding the use of 16- or 24-μL/kg BAM for immobilizing rhesus macaques is dependent on caution regarding cardiopulmonary parameters and the provision of supplemental oxygen.

The catecholamine neurotransmitter dopamine (DA) exerts powerful modulatory control of physiology and behavior across phylogeny. Perturbations of DA signaling in humans are associated with multiple neurodegenerative and behavioral disorders, including Parkinson's disease, attention-deficit/hyperactivity disorder, addiction and schizophrenia. In the nematode C. elegans, DA signaling regulates mating behavior, learning, food seeking and locomotion. Previously, we demonstrated that loss of function mutations in the dat-1 gene that encodes the presynaptic DA transporter (DAT-1) results in a rapid cessation of movement when animals are placed in water, termed Swimming Induced Paralysis (Swip). Loss of function mutations in genes that support DA biosynthesis, DA vesicular packaging and DA action at the extrasynaptic D2-type DA receptor DOP-3 suppress Swip in dat-1 animals, consistent with paralysis as arising from excessive DA signaling. Although animals grown on the vesicular monoamine transporter antagonist reserpine diminish Swip, the drug must be applied chronically, can impact the signaling of multiple biogenic amines, and has been reported to have penetrant, off-target actions. Here, we demonstrate that the antipsychotic drug azaperone potently and rapidly suppresses Swip behavior in either dat-1 mutants, as well as in wildtype animals treated with the DAT-1 antagonist nisoxetine, with genetic experiments consistent with DOP-3 antagonism as the mechanism of Swip suppression. Reversal of Swip in previously paralyzed dat-1 animals by azaperone application demonstrates an otherwise functionally-intact swimming circuit in these mutants. Finally, whereas azaperone suppresses DA-dependent Swip, the drug fails to attenuate the DA-independent paralysis induced by βPEA, aldicarb or genetic disruption of γ-aminobutyric acid (GABA) signaling. We discuss our findings with respect to the use of azaperone as a potent and selective tool in the identification and analysis of presynaptic mechanisms that regulate DA signaling., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: The butorphanol-azaperone-medetomidine fixed-dose combination (BAM, respectively, 30-12-12 mg mL -1 ) with subsequent antagonism by naltrexone-atipamezole was evaluated for reversible immobilization of captive cheetahs (Acinonyx jubatus)., Study Design: Prospective, clinical trial., Animals: Twelve cheetahs (six males and six females, weighing 37-57 kg) housed in enclosures, were immobilized at Hoedspruit Endangered Species Centre in the Republic of South Africa., Methods: BAM volume dose rate was 0.009-0.014 mL kg -1 (mean ± standard deviation 0.010 ± 0.001 mL kg -1 ). Total dose in all animals was 0.5 mL. The actual doses were as follows: butorphanol (0.29 ± 0.04 mg kg -1 ), azaperone (0.12 ± 0.01 mg kg -1 ) and medetomidine (0.12 ± 0.01 mg kg -1 ). Physiologic variables and quality of immobilization were recorded every 5 minutes beginning at 15-20 minutes after darting. Arterial blood samples were collected three times at 20, 30 and 40 minutes after darting from all animals for analysis of blood oxygenation and acid-base status., Results: The inductions were calm and smooth and mean induction time was 4.0 ± 1.1 minutes. Heart rate (50 ± 9 beats minute -1 ) and respiratory frequency (20 ± 3 breaths minute -1 ) were stable throughout immobilization. The recovery time after reversing with naltrexone and atipamezole was 9.1 ± 3.6 minutes., Conclusions: and clinical relevance BAM proved to be a reliable and cardiovascular stable drug combination for immobilization of cheetahs., (Copyright © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

To assess potential seasonal differences in responses to immobilization, we sedated eight orphaned yearling black bears ( Ursus americanus) being held for rehabilitation at a wildlife facility in Colorado, US, using a premixed combination of nalbuphine (40 mg/mL), azaperone (10 mg/mL), and medetomidine (10 mg/mL; NalMed-A) in October (autumn) prior to hibernation and again after emergence in May (spring) prior to their release. We dosed all bears at 1 mL NalMed-A per estimated 45 kg body mass (1 mL NalMed-A/45 kg), delivered by intramuscular injection using a pole syringe, to facilitate routine examination and ear tagging. Arterial blood gases were measured to assess oxygenation and acid-base status of bears both pre and post oxygen supplementation. The mean (SE) dose calculated post hoc was 0.9 (0.04) mg nalbuphine/kg, 0.2 (0.01) mg azaperone/kg, and 0.2 (0.01) mg medetomidine/kg. The mean induction time was 8 (1) min for six of the bears in October and 6 (1) min for eight bears in May. The NalMed-A combination provided good sedation in captive yearling black bears in autumn and spring and was effectively antagonized with a combination of naltrexone and atipamezole. Mild hypoxemia (PaO 2 : 53.5-54.4 mmHg) was the most significant side effect and was corrected (PaO 2 : 68.4-150.1 mmHg) with supplemental oxygen administered at 2-5 L/min for 5 min (point of sampling).

Decreased access to potent narcotics for wildlife applications has stimulated the need to explore alternative drug combinations for ungulate immobilizations. A combination of butorphanol, azaperone, and medetomidine (BAM) has been used for some ungulate species, but information on its use in bison ( Bison bison) is limited. We conducted field trials using BAM, in conjunction with atipamezole and naltrexone as antagonists, for reversible field immobilization of bison during ground- and helicopter-based operations. We compared times to induction and recovery, vital rates (rectal temperature and respiration rate), and the quality of induction, immobilization, and recovery between ground- and helicopter-based immobilizations of bison. Overall, 15 of 21 bison were induced with the volume we used (mean±SD=3.4±0.6 mL); two other animals darted from a helicopter required a full second dose, and four others (two darted from the ground and two from a helicopter) required a supplemental partial dose to achieve induction. All immobilizations achieved a sufficient plane of anesthesia to permit minor invasive procedures (e.g., skin biopsy and blood sampling). All animals recovered, and most (17 of 21) were reversed in ≤5 min. The mean time to induction was 10.8±7.3 min while that for recovery was 5.0±2.1 min. We found few differences in vital rates or the quality of immobilizations between ground- and helicopter-based captures. The drug combination provided good immobilization and was reliably reversed; however, inconsistent inductions at the doses we used may limit its use in field immobilizations of bison, particularly those animals being darted from a helicopter.

Azaperone can reduce stress caused by weaning and relocation of breeding sows, but its effects on reproductive processes are still poorly understood. The primary aim of this study was to describe and compare the endocrine and ovarian activity in ultrasonographically monitored second parity sows, with or without azaperone treatment at weaning (2 mg/kg BW i.m.). The intervals from weaning to the onset of estrus and ovulation were both greater (P<0.05) in azaperone-treated (n=12) than in control sows (n=12) by ~12 h. Mean daily growth rates of identified antral follicles were less (P<0.05) in azaperone-treated than in control sows (1.08±0.17 v.1.23±0.18 mm/day; mean±SD) and treated animals exceeded (P<0.05) controls in the mean ovulation rate (13.7±1.3 v. 12.6±1.2). A transient suppression of cortisol release was observed in the treatment group (at 10 and 30 min after azaperone injections) but circulating cortisol concentrations were variable in both groups of sows for the remainder of the study. The preovulatory rise in LH and estradiol secretion was delayed (P<0.05), and the duration of the LH surge was greater (P<0.001) in azaperone-treated sows compared with their control counterparts. The amplitude of episodic fluctuations in serum cortisol concentrations was correlated with the number of stillborn piglets in control sows (r=0.63, P=0.04). The amplitude and concentration of the preovulatory rise in estradiol secretion were negatively correlated with ovulatory response and litter size (r=-0.63 to -0.82, P<0.05), whereas the time at which the LH surge ended was directly related to the number of live-born piglets (r=0.82, P=0.002) in azaperone-treated animals. The present results indicate that administration of azaperone at weaning had a profound effect on preovulatory LH secretion as well as growth kinetics and estrogenicity of ovarian antral follicles. However, the causative associations among various characteristics of the preovulatory LH discharge, ovarian and adrenal steroid secretion post-weaning, and reproductive variables in sows remain equivocal.

Chemical immobilization is a key aspect of wildlife management. To minimize dose-dependent adverse effects, immobilization protocols often include two or more synergistic agents, which allows for reductions in individual drug dosages. Free-ranging bighorn sheep ( Ovis canadensis) in Canada ( n = 74) were remotely injected with a combination of medetomidine (0.16 ± 0.04 mg/kg) and ketamine (4.0 ± 1.4 mg/kg) (MK), or combination of medetomidine (0.14 ± 0.06 mg/kg), azaperone (0.21 ± 0.11 mg/kg), and alfaxalone (0.45 ± 0.21 mg/kg) (MAA). Once recumbency was achieved, arterial blood samples were collected and immediately analyzed for blood gas and acid-base status. Rectal temperature, heart rate, and respiratory rate were recorded upon recumbency and throughout anesthesia at 5-15 min intervals. At conclusion of the procedures, medetomidine was reversed by intramuscular atipamezole at five times the medetomidine dose. Induction times (mean ± standard deviation) of animals that became immobilized with one dart (8.7 ± 3.2 min, 7.3 ± 3.9 min) and recovery times of all animals (3.4 ± 1.5 min, 3.9 ± 1.6 min) were not significantly different between MK and MAA groups, respectively. Both MK and MAA groups experienced severe hypoxemia (PaO 2 42 ± 9 mmHg, 40 ± 10 mmHg, respectively). PaCO 2 was significantly higher ( P = 0.0248) in the MK group (median 54 mmHg) than the MAA group (median 48 mmHg) with a trend towards lower pH (7.40 vs 7.42, respectively, P = 0.07). Initially, MK animals had higher heart rates than MAA animals (median 49 vs 40 beats/min), which decreased over time. In bighorn sheep, both MK and MAA produced reliable, reversible immobilization with smooth inductions and recoveries. However, less respiratory depression was seen with MAA than MK.

A combination of butorphanol-azaperone-medetomidine was used to immobilize four captive caribou ( Rangifer tarandus granti) in Palmer, Alaska, US. The average induction time for this combination was 5:17±2:06 min. Inductions were smooth, and recoveries were excellent. This drug combination may provide an alternative to the use of potent opioids for immobilizing caribou.

Various anesthetic protocols are used in laboratory swine, each with specific advantages and disadvantages. Partial intravenous anesthetic techniques (PIVA) help minimize dose-dependent cardiopulmonary effects of inhalant drugs. The aim of this study was to determine the cardiopulmonary effects of a PIVA in laboratory swine. In a prospective, nonrandomized clinical study, 8 healthy juvenile Landrace-White pigs were premedicated with azaperone (0.20 ± 0.20 mg/kg IM), dexmedetomidine (0.02 ± 0.002 mg/kg IM), and alfaxalone (2.0 ± 0.20 mg/kg IM), and anesthesia was induced with intravenous alfaxalone. Anesthesia was maintained by using constant-rate infusion of dexmedetomidine (2 μg/kg/h) and alfaxalone (25 μg/kg/min) in combination with isoflurane. After the fraction of expired isoflurane was adjusted to 1.1% to 1.5%, respiratory rate, heart rate, systemic and pulmonary arterial pressure, central venous pressure, cardiac output, bispectral index, systemic vascular resistance, and arterial and mixed venous blood gases were recorded every 10 min for 60 min. Statistical analysis consisted of repeated-measures one-way ANOVA. Significant decreases occurred in heart rate, pulmonary mean arterial pressure, pulmonary diastolic pressure, partial pressure of arterial oxygen, partial pressure of venous oxygen; significant increases occurred in respiratory rate, minute volume index, diastolic arterial blood pressure, systemic vascular resistance, and arterial pH over time. We consider that the observed statistically significant cardiopulmonary changes were clinically important and that the PIVA protocol provided hemodynamic and respiratory stability for short-term anesthesia of laboratory swine.

A total of 58 American beavers ( Castor canadensis) was immobilized with butorphanol, azaperone, and medetomidine (BAM) for the purpose of health assessments, sex determination, and placement of very high-frequency tail transmitters in a subset of animals. Isoflurane gas anesthesia was available to aid with induction when needed, and all animals received supplementary oxygen. Thirty-one beavers immobilized with a mean (SD) dose of 0.65 (0.15) mg/kg butorphanol, 0.22 (0.05) mg/kg azaperone, and 0.26 (0.06) mg/kg medetomidine did not require supplemental isoflurane during induction and the mean induction time was 8 min (range: 3-21 min). This dose was equivalent to 0.024 (0.005) mL of BAM per kilogram. A total of 29 beavers that were immobilized with a mean (SD) of 0.51 (0.07) mg/kg butorphanol, 0.17 (0.02) mg/kg azaperone, and 0.2 (0.03) mg/kg medetomidine needed supplementary isoflurane at 5% and 5 L/min for <1 min to induce full anesthesia. In none of the beavers did BAM alone provide sufficient depth of anesthesia to drill a hole in the tail for transmitter placement, and supplementary isoflurane was administered to reach a sufficient level of analgesia for the procedure. The beavers were reversed with 5 mg of atipamezole per milligram of medetomidine and 1 mg of naltrexone per milligram of butorphanol. No adverse effects or mortalities were observed. Butorphanol-azaperone-medetomidine can be considered safe for use in American beavers for minor procedures.

Wildlife anesthetic protocols must offer rapid inductions and recoveries, be physiologically safe, and be minimally regulated. With this in mind, we evaluated differences in induction and recovery times and physiological parameters in 33 American black bears ( Ursus americanus) anesthetized with ketamine-xylazine (KX) or immobilized with a commercial drug combination of butorphanol, azaperone, and medetomidine (BAM). Dose was based on mass estimated from field observations. Bears were housed at Appalachian Bear Rescue, Townsend, Tennessee, US, or free-ranging within the Great Smoky Mountains National Park (Tennessee and North Carolina, US) and chemically immobilized for management purposes. From 11 April to 29 June 2016, we immobilized bears with injection via pole syringe or disposable dart projected from an air-powered dart rifle. Once immobilized, we measured each bear's temperature, respiration (breaths/min), heart rate (beats/min), hemoglobin oxygen saturation (via pulse oximetry), arterial blood gases, and mass (kg). We found no differences in the induction parameters, partial pressures of CO 2 , and rectal temperatures. The BAM-treated bears had lower heart and respiratory rates that led to lower hemoglobin oxygen saturation levels (from blood gas analysis, SaO 2 ). The SaO 2 after treatment with BAM (91.1±0.8%) was lower than with KX (93.4±0.9%). After handling, we reversed KX-treated bears with a x̄=0.2±0.02 mg/kg yohimbine and BAM-treated bears with x̄=1.5±0.1 mg/kg atipamezole and 0.8±0.1 mg/kg naltrexone. We found no differences in the recovery times to increased respiration and to the bear assuming a head-up position. The BAM-treated bears stood and recovered quicker than did KX-treated animals. Based on our observations, BAM appears to offer safe, predictable immobilizations with fewer drawbacks and faster recovery times than KX-treated bears.

Previous studies demonstrated that nalbuphine, medetomidine, and azaperone (NalMed-A) can effectively immobilize adult elk ( Cervus elaphus nelsoni), and be antagonized using naltrexone and atipamezole, with or without tolazoline. To assess duration of tissue residues for this immobilization package, we immobilized 14 captive adult elk with NalMed-A, then euthanized animals and collected tissues 0, 3, 6, 14, 21, or 28 d later. Except for two animals euthanized immediately, all elk were recovered using naltrexone, atipamezole, and tolazoline. Tissue residues (≥0.01 parts per million) for the tranquilizers nalbuphine, medetomidine, and azaperone were detected in liver and muscle tissue samples from elk euthanized within 40 min postinjection (PI) and one animal that died 12-24 h PI, but not in tissues from any of the animals euthanized at 3, 6, 14, 21, or 28 d PI. Tissue residues for the antagonists naltrexone, atipamezole, and tolazoline were detected in liver and muscle of the animal that died 12-24 h PI. Only naltrexone was detected in liver from the two elk euthanized at day 3, and no antagonist residues were detected thereafter.

Records of 56 Persian fallow deer (Dama dama mesopotamica) immobilized for translocation were reviewed. Twenty-three were administered 0.05 ± 0.01 (mean ± SD) mg/kg thiafentanil (THIA), 20 were administered 0.045 ± 0.008 mg/kg thiafentanil combined with 0.19 ± 0.03 mg/kg azaperone (THIA-AZP), and 13 were administered 0.032 ± 0.04 mg/kg etorphine-acepromazine (ETOR-ACP) by intramuscular remote injection. Parameters recorded and compared between groups included induction and recovery times, heart rate, respiratory rate, rectal temperature, oxygen saturation, blood pressure, reflexes, quality of immobilization, and blood concentrations of lactate and glucose. Naltrexone (THIA groups) or diprenorphine (ETOR-ACP) were administered for reversal. Mean induction time was significantly shorter in the THIA group versus the ETOR-ACP group (2.0 ± 1.3 and 4.8 ± 2.8 min, respectively), but not significantly shorter than the THIA-AZP group (2.8 ± 3.1 min). Respiratory rate was significantly higher in the THIA group in comparison to the two other groups. None of the protocols provided excellent immobilization quality, which was significantly poorer in the THIA group. Following antagonist administration, all deer from the THIA and ETOR-ACP groups recovered quickly, while there were five perianesthetic morbidity and mortality cases in the THIA-AZP group. Mean recovery time was significantly shorter in the THIA group versus the THIA-AZP and ETOR-ACP groups (0.5 ± 0.3, 1.1 ± 0.8, and 2.3 ± 1.1 min, respectively). In conclusion, the use of THIA provided faster induction and recovery, with less respiratory depression, but poorer immobilization. The THIA-AZP combination should be used with caution in Persian fallow deer until further investigation.

The aim of this current study was to evaluate the level of anesthesia produced by a combination of butorphanol-azaperone-medetomidine (BAM) for semen collection by electroejaculation on captive white-tailed bucks (Odocoileus virginianus). Ten male white-tailed deer, weighing 68.2-115.9kg, ranging in age from one to four years were randomly selected from housing pens and anesthetized with the BAM drug combination at a dose volume of 2.0mL each. Semen was collected from each animal using a standard cervid electroejaculation protocol while under BAM anesthesia. Physiological data was recorded following induction of anesthesia and during semen collection. Collected ejaculates were prepared for analysis using a standard extender protocol for cryopreservation. Eleven sperm viability parameters were quantified for each sample using a Computerized Assisted Sperm Analysis system, including total seminal volume; sperm concentration and total sperm number. kinematic parameters of motile spermatozoa were also assessed. Results demonstrated that BAM provided an effective plane of anesthesia for successful collection of viable sperm. Measured physiological variables of heart rate, respiration and body temperature all remained within safe, normal limits. Data recorded on semen characteristics from all collected ejaculates correlated well with key traits determined to be important for successful fertilization through measurement of total semen volume; sperm concentration; total sperm number; and kinematic parameters of motile spermatozoa. There were no serious adverse events. This field study indicates that BAM anesthesia is suitable for semen collection in white-tailed deer., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Experimental setups for physiological research, in which acute operative interventions need to be performed, can require inclusion of general anesthesia (GA), which may interfere or confound with the effects of the experimental factors of interest on measured variables. It was recently shown that the most commonly used sedatives/anesthetics in pigs (e.g., ketamine, xylazine, azaperone) affect physiological responses and thus the primary metabolic readouts have the potential to be confounded. To extend the search for a physiologically-friendly anesthesia regime for such studies, we investigated effects of GA induced by propofol (Prop) or pentobarbital (Pent) or propofol plus isoflurane (Prop + Isof) on plasma concentrations of commonly measured metabolites and hormones. In 2 experimental runs, 6 female pigs fitted with jugular vein catheters were used. Fasted pigs received either no drug (CON) or anesthetized rotationally either with Prop, Pent or Prop + Isof on different days, separated with washout periods of sufficient length (2 to 3 d). Six-h profiles of glucose, lactate, non-esterified fatty acids (NEFA), triglycerides (TG), cholesterol, urea as well as hormones including glucagon, insulin and cortisol were determined. Concentrations of cholesterol, urea and glucagon remained unaffected by any of the treatments ( > 0.05). Pent tended to increase cortisol from 30 to 90 min after drug administration. Glucose and lactate concentrations were increased ( < 0.05) by Prop and Pent within the first hour of GA ( < 0.05). Propofol and Pent reduced NEFA concentrations, which were more pronounced during the last 2 h of the studied period. Triglyceride concentrations were increased by all 3 agents within the first 45 min with Prop containing treatments exerting a stronger effect than Pent. Our data suggest that GA with Prop and particularly with Pent adulterate plasma metabolite and hormone profiles of pigs acutely, and thus has the potential to confound the effects of experimental factors of interest. Although Prop + Isof anesthesia did not differ from the controls, providing a physiologically-friendly GA, both single and the isoflurane-combined treatment of Prop induced hypertriglyceridemia due to the lipid adjuvant of the Prop drugs. It is concluded that readouts obtained under GA may be influenced both by physiological adulterations as response to anesthesia as well as by artifacts due to accompanying ingredients of the drug formulations.

The objective of this study was to compare a traditional partially reversible medetomidine-ketamine sedation with a more reversible butorphanol-azaperone-medetomidine combination in Bennett's wallabies ( Macropus rufogriseus ) maintained in a zoological collection. Fourteen animals were divided into two treatment groups. Individuals in group 1 received an intramuscular (i.m.) injection of butorphanol (0.54 ± 0.05 mg/kg), azaperone (0.22 ± 0.02 mg/kg), and medetomidine (0.16 ± 0.02 mg/kg). Individuals in group 2 received an i.m. injection of ketamine (5.43 ±1.16 mg/kg) with medetomidine (0.05 ± 0.014 mg/kg). For group 1, sedation was reversed with atipamezole (0.81 ± 0.069 mg/kg i.m.) and naltrexone (1.08 ± 0.09 mg/kg i.m.). For group 2, sedation was reversed with atipamezole (0.27 ± 0.056 mg/kg i.m.). There were no significant differences between the groups in mean time to induction, time spent on gas anesthesia, or time to standing after reversal was administered. Animals in both groups required supplemental gas anesthesia to facilitate intubation. No adverse reactions or effects were noted with either protocol; however, the BAM protocol did not provide sufficient sedation for handling in all animals and may not be suitable for use in this species.

Chemical capture is an essential tool in the management and conservation of white rhinoceros ( Ceratotherium simum ); however, cardiovascular responses in immobilized megaherbivores are poorly understood. Blood pressure and heart rate responses in rhinoceros immobilized with etorphine or etorphine plus azaperone, and the effects of subsequent i.v. butorphanol administration were investigated. Six white rhinoceros were used in a randomized crossover study design with four interventions: 1) etorphine i.m.; 2) etorphine plus azaperone i.m.; 3) etorphine i.m. and butorphanol i.v.; and 4) etorphine plus azaperone i.m., and butorphanol i.v. Etorphine resulted in hypertension and tachycardia in immobilized rhinoceros on initial measurements. Over the 25-min study period, blood pressures and heart rate declined. Heart rates were slower, although the rhinoceros were still tachycardic, and blood pressures lower during the whole study period in animals immobilized with etorphine and azaperone compared with those that received only etorphine. Butorphanol administration resulted in lower arterial blood pressures and heart rates in etorphine-immobilized rhinoceros. In rhinoceros immobilized with etorphine and azaperone, heart rate slowed following administration of butorphanol i.v., although blood pressures remained unchanged. Azaperone reduced hypertension associated with etorphine immobilization, but animals remained tachycardic. Administration of butorphanol to etorphine/azaperone-immoblized rhinoceros lowered heart rate to values approaching normal resting levels without altering blood pressure.

Physiological research with swine often includes sedation or general anesthesia (GA), which may influence the basal physiological responses of experimental animals and may have the potential to confound or interfere with the effects of experimental factors of interest. Using 6 adult female pigs, we investigated whether selected plasma metabolites and hormones are influenced by GA induced with ketamine (K) and 2 neuroleptic sedatives, namely azaperone (A) and xylazine (X). Fasted pigs rotationally received either no drug, a single intravenous administration of A or X, or A or X combined with ketamine (AK or XK, respectively), and plasma concentrations of glucose, lactate, non-esterified fatty acids (NEFA), triglycerides (TG), glucagon, insulin, and cortisol were determined for a 5-h period following administration. Azaperone and X induced deep sedation, whereas AK and XK induced GA. Overall, the average plasma glucose concentrations were increased by A and X, with the latter exerting a stronger effect that was also associated with hypoinsulinemia ( < 0.05). Time-dependent effects indicated a more rapid increase in glucose concentration due to X or XK than AK. Plasma NEFA concentrations were elevated by A and AK and to a lesser extent by X and XK ( < 0.05). Plasma lactate and TG levels were elevated by A and AK and remained unaffected by X or XK. Plasma cortisol concentrations were elevated ( < 0.05) by X and XK and even more so with a single administration of A ( < 0.05), while the combined effect of A with ketamine resulted in the highest cortisol concentrations ( < 0.05). Our data suggest that the effects of azaperone are mediated by cortisol but less so for xylazine, which also indicates that azaperone elicits a stronger stress response in pigs. Xylazine probably induces long-lasting, fasting-state hyperglycemia through the stimulation of hepatic glucose production associated with hypoinsulinemia. A discriminant analysis based on the variation in all of the measured metabolites and hormones, collectively, indicated that ketamine induced no additional effect on the overall physiological response patterns than that of the individual sedatives. In conclusion, the neuroleptic sedatives azaperone, and to a lesser extent, xylazine, acutely affect the metabolism of pigs, so primary metabolic readouts obtained under these drugs may be confounded.

Carfentanil-xylazine (CX) has been the primary drug combination used for immobilizing free-ranging ungulates in Alaska, US since 1986. We investigated the efficacy of a potential new drug of choice, thiafentanil (Investigational New Animal Drug A-3080). Captive trials indicated that thiafentanil-azaperone-medetomidine could provide good levels of immobilization. However, field trials conducted in October 2013 on free-ranging caribou ( Rangifer tarandus granti) calves showed the combination too potent, causing three respiratory arrests and one mortality. The protocol was revised to thiafentanil-azaperone-xylazine (TAX), with good results. The induction time was not significantly different between the two combinations. However, the recovery time was significantly shorter for the TAX group than for the CX group. A physiologic evaluation was performed on 12 animals immobilized on CX and 15 animals on TAX. Arterial blood was collected after induction and again after 10 min of intranasal oxygen supplements (1 L/min). Both groups had significant increases in partial pressure of arterial oxygen after oxygen treatment. There was a concurrent significant increase in partial pressure of arterial carbon dioxide in both groups. Rectal temperature increased significantly in both groups during the downtime, which is consistent with other studies of potent opioids in ungulates. On the basis of our results, we found TAX to be a potential alternative for the current CX protocol for immobilizing free-ranging caribou calves via helicopter darting.

Alfaxalone is a neurosteroid that interacts with gamma-aminobutyric type A receptors to produce central nervous system depression and muscle relaxation. The effects of alfaxalone vary from sedation to general anesthesia. Alfaxalone is synergistic with other tranquilizers and sedatives and therefore has the potential to improve existing alpha-2 adrenergic agonist-based combinations used for wildlife immobilization. The objective of this study was to determine the efficacy and cardiopulmonary effects of a medetomidine-azaperone-alfaxalone (MAA) combination in captive white-tailed deer (Odocoileus virginianus). Eight captive white-tailed deer were restrained in a drop-floor chute; hand injected i.m. with 0.15 mg/kg medetomidine, 0.2 mg/kg azaperone, and 0.5 mg/kg alfaxalone; and released into a small enclosure for observation. The deer were maintained in lateral recumbency for a total time from postinjection (PI) of the drug of 60 min. At 60 min PI, atipamezole was administered i.m. at five times the medetomidine dose. Heart rate, respiratory rate, rectal temperature, and direct systolic, mean, and diastolic arterial blood pressures were recorded every 5 min. Arterial blood samples were taken every 15 min for blood gas analysis. Level of sedation and quality of recovery were scored. Statistical analysis was performed using analysis of variance and descriptive statistics with a significance level of P < 0.05. Induction (time to lateral recumbency, 7.1 ± 2.4 min (mean ± SD) and recovery times (time to standing, 9.1 ± 3.1 min) were comparable to currently used medetomidine-based combinations in white-tailed deer. Major cardiopulmonary effects observed (values reported are 15 min PI of immobilizing drugs) were hypoxemia (PaO2, 54 ± 9 mm Hg), hypoventilation (PaCO2, 55 ± 3 mm Hg), and mixed acid-base disturbances (pH, 7.22 ± 0.04). No adverse effects were observed after recovery from anesthesia. MAA produced a satisfactory level of deep sedation for safe handling and minor procedures in captive white-tailed deer.