PROTOCOL FOR HUMAN EXPOSURE TO OPIOIDS AND CONCENTRATED MEDETOMIDINE USED IN FIELD APPLICATIONS.

Wildlife professionals routinely use potent sedatives and anesthetics when chemically immobilizing wildlife and zoo species in remote environments. Accidental exposure to these prescription veterinary drugs is rare but could be rapidly fatal. Commonly used agents include opioids and α2 adrenoreceptor agonists. These drugs can be reversed with specific antagonists; however, they are often not approved for human use. The protocol created here can be used by wildlife health professionals in a field setting with basic human emergency medical response training in coordination with local Emergency Medical Services (EMS). Key components include, building local relationships between EMS and wildlife professionals, focused EMS training, administering opioid and α2 adrenergic antagonists off label, and local evacuation procedures. This framework could allow wildlife management agencies or zoos to mitigate the risk of human exposures to these commonly used drugs, significantly improving occupational safety in an otherwise high-risk environment.

Safety and Efficacy of Nalbuphine, Medetomidine, and Azaperone for Immobilizing Aoudad (Ammotragus lervia).

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.

Tissue Residue Levels after Immobilization of Rocky Mountain Elk ( Cervus elaphus nelsoni) using a Combination of Nalbuphine, Medetomidine, and Azaperone Antagonized with Naltrexone, Atipamezole, and Tolazoline.

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.

THE EFFICACY OF NALBUPHINE, MEDETOMIDINE, AND AZAPERONE IN IMMOBILIZING AMERICAN BISON (BISON BISON).

We evaluated a combination of nalbuphine, medetomidine, and azaperone (NalMed-A) in 12 American bison ( Bison bison ) during 13 sedation handling events. The mean (SE) dosage was 0.4 (0.02) mg/kg nalbuphine, 0.08 (0.003) mg/kg medetomidine, and 0.08 (0.003) mg/kg azaperone contained in an average delivery volume of 0.8 mL/100 kg. Two animals required a supplemental dose for safe handling (additive dose used in calculating means) and a third animal was not adequately sedated despite a supplemental dose. Bison immobilized with NalMed-A showed good sedation in 12 of 13 handling attempts. Advantages of this drug combination included a relatively low delivery volume, rapid antagonism, and minimal regulatory burden for component drugs. The most consistent disadvantage was hypoxemia, and oxygen supplementation is recommended when using this sedative combination in bison.

Novel combinations of nalbuphine and medetomidine for wildlife immobilization.

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.

Butorphanol, azaperone, and medetomidine anesthesia in free-ranging white-tailed deer (Odocoileus virginianus) using radiotransmitter darts.

Fourteen free-ranging white-tailed deer (Odocoileus virginianus) were successfully anesthetized for a total of 15 anesthetic events using a combination of butorphanol (mean+/-SD, 0.58+/-0.1 mg/kg), azaperone (0.37+/-0.06 mg/kg), and medetomidine (0.19+/-0.03 mg/kg) (BAM) administered by radiotelemetry darts from hunting blinds between November 2006 and May 2007. Mean time to locate deer (mean+/-SD, 17. 3+/-7 min), to recumbency (21.4+/-5 min), to initiation of data acquisition (27.5+/-8 min), total down time (37+/-6 min), and average distance run (161+/-82 m) were recorded. Physiologic monitoring was done every 5 min for a total of 20 min. Arterial blood gases were collected every 10 min. Mild to moderate hypoxemia and mildly depressed ventilation occurred in some animals. Muscle relaxation and plane of anesthesia were adequate for completion of all procedures; two deer were administered intravenous butorphanol supplementation to achieve light anesthesia (mean+/-SD, 0.19 mg/kg; 0.12 mg/kg). Recovery following intramuscular administration of naltrexone (1.34+/-0.42 mg/kg; 2x butorphanol dose) and atipamezole (0.93+/-0.14 mg/kg; 5x medetomidine dose) was rapid, smooth, and complete. Mean+/-SD recovery time was 4.5+/-1.5 min. Overall efficacy of the Pneu-Dart radiotelemetry system was 65%. Negative attributes of this protocol included long induction time and dart failure. No known mortalities occurred as a result of the study. This drug combination provided safe, reliable, short-term anesthesia of free-ranging white-tailed deer. Further evaluation for use in field procedures in other cervids is warranted.

Butorphanol-azaperone-medetomidine for immobilization of captive white-tailed deer.

Drug combinations are commonly used to immobilize white-tailed deer (Odocoileus virginianus) for capture or handling. Although efficacy of various compatible and complementary drugs has been tested in clinical trials with deer, extensive negative side effects, impractical drug volume, and slow recovery from immobilization sometimes make these combinations less than ideal for routine field use. We hypothesized that a combination of butorphanol, azaperone, and medetomidine (BAM) would provide safe and effective immobilization of captive white-tailed deer while minimizing these complicating factors. We tested two dosages of this drug combination (BAM-1 and BAM-2) and two dosages of a naltrexone, tolazoline, and atipamezole antagonist combination (NTA-1 and NTA-2) with captive white-tailed deer. We characterized efficacy of drug for immobilization, quality of drug induction, and recovery after drug reversal, and we compared our findings with those of previous drug trials. Complete immobilization and excellent induction quality was achieved with a low volume dosage of BAM-2. Time to drug induction and deer recumbency for BAM-2 compared favorably with results from previous trials involving xylaxine/ ketamine and medetomidine/ketamine but without risk of hyperthermia. We found no differences in time to deer recovery for NTA-1 and NTA-2, with deer treated with either combination standing by 30 min postinjection. Regardless of immobilizing drugs used, we suggest practitioners monitor for signs of circulatory deficiency in deer and provide supplemental oxygen when needed.

Evaluation of intramuscular butorphanol, azaperone, and medetomidine and nasal oxygen insufflation for the chemical immobilization of white-tailed deer, Odocoileus virginianus.

Chemical immobilization of wildlife often includes opioids or cyclohexamines. These substances are problematic as a result of their required storage, handling, and record-keeping protocols. A potentially useful alternative sedation protocol includes a combination of butorphanol, azaperone, and medetomidine (BAM: 0.43 mg/kg butorphanol, 0.36 mg/kg azaperone, 0.14 mg/kg medetomidine). One risk of wildlife immobilization with any drug combination is hypoxemia. This may be of particular importance when using an alpha 2 agonist such as medetomidine because of its powerful vasoconstrictive effect. In this prospective study, the BAM combination was evaluated for chemical immobilization of white-tailed deer. Additionally, selected physiologic parameters associated with BAM immobilization, including oxygen saturation via pulse oximetry and arterial blood gas measurement, with and without nasal insufflation of oxygen at a relatively low flow of 3 L/min, were evaluated. The BAM combination resulted in a predictable onset of sedation, with a mean induction time to lateral recumbency of 9.8 +/- 3.6 min. All deer recovered smoothly within a range of 5-20 min after reversal with intramuscular administration of naltrexone, atipamazole, and tolazoline (NAT). Clinically relevant decreases in arterial partial pressure of oxygen (PaO2) and oxygen saturation (SpO2) were observed in animals not receiving supplemental oxygen, while both parameters significantly improved for oxygen-supplemented deer. Pulse oximetry with this protocol was an unreliable indicator of oxygen saturation. In this study, altitude, recumbency, hypoventilation, butorphanol- and medetomidine-specific effects, as well as the potential for alpha 2 agonist-induced pulmonary changes all may have contributed to the development of hypoxemia. Overall, capture of white-tailed deer with the BAM/NAT protocol resulted in excellent chemical immobilization and reversal. Because the BAM combination caused significant hypoxemia that is unreliably detected by pulse oximetry but that may be resolved with nasal oxygen insufflation, routine use of oxygen supplementation is recommended.

Immobilization of mule deer with thiafentanil (A-3080) or thiafentanil plus xylazine.

We evaluated thiafentanil oxalate (A-3080) for the immobilization of mule deer (Odocoileus hemionus) under laboratory and field conditions. In a crossover experiment comparing recommended (0.1 mg/kg) and 2x recommended thiafentanil doses in captive deer, both produced rapid induction and immobilization. Mean induction was shorter (P = 0.013) for the 2x group (1.9 vs. 3 min); mean reversals for both groups were rapid (recommended = 0.9 min after naltrexone injection; 2x = 1 min) and did not differ (P = 0.29). Six free-ranging mule deer were immobilized with 7 mg thiafentanil and four with 10 mg; mean induction was 2.3 min for both groups (95% confidence interval [CI]: 7 mg, 1.2-3.4; 10 mg, 1.9-2.8), and mean reversal was <1 min for both groups. Of 165 free-ranging deer darted with various combinations of thiafentanil and xylazine, we successfully immobilized 148 (90%). Mean induction ranged from 2.1 to 4.9 min for different drug combinations. Reversals were not compared because naltrexone and yohimbine doses varied, but overall mean reversal was 1.9 min (95% CI, 1.7-2.1 min) after injection of naltrexone and yohimbine intravenously (i.v.); naltrexone:thiafentanil ratios ranging from 10:1 to 43:1 provided mean recoveries ranging from 1.5 to 2.3 min. All 25 deer fitted with radio collars were alive at 30 days postcapture. On the basis of overall reliability and effectiveness, drug volumes, and ease of handling drugged animals, we recommend using a combination of 10-12 mg thiafentanil (0.15-0.2 mg/kg) and 100 mg xylazine to immobilize mule deer; immobilization can be effectively reversed with 100 mg naltrexone or more and 15 mg yohimbine or more i.v. Where feasible, we also recommend the use of transmitter darts when immobilizing mule deer with opioids in order to maximize recovery of darted deer and to ensure that missed darts are found.