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Anaesthesia of nyala (Tragelaphus angasi ) with a combination of thiafentanil (A3080), medetomidine and ketamine

D V Coopera, D Groblerb, M Bushc*, D Jessupd and W Lancee

receptor binding affinity of 10 times that ABSTRACT of the sedative xylazine11,20. Medetomidine A combination of thiafentanil (A3080), medetomidine hydrochloride (MED) and ketamine is a potent sedative and analgesic with hydrochloride (KET) was evaluated in 19 boma-habituated (12 female and 7 males) and 9 anxiolytic properties11,19 and at high doses free-ranging nyala (7 male and 2 females) (Tragelaphus angasi) to develop a safe and reliable has hypnotic or anaesthetic effects19. anaesthesia protocol. Wide dosages were used safely during this study with ranges for Medetomidine provides good muscle A3080 of 45 ± 8 µg/kg with MED of 69 ± 19 µg/kg and KET of 3.7 ± 1.0 mg/kg (200 mg/ relaxation with minor physiological animal). The dosages developed on boma-habituated nyala proved to be equally effective changes in Arabian oryx (Oryx leucoryx)8 in 9 adult free-ranging nyala (7 males and 2 females). The optimum dosage for nyala was a and when combined with ketamine hy- combination of A3080 (40–50 µg/kg), MED (60–80 µg/kg) plus 200 mg of KET/animal. The drochloride (KET) has been demon- anaesthesia was characterised by a short induction, good muscle relaxation and mild strated to be effective in a broad range of hypoxaemia during monitoring the anaesthesia was rapidly and completely reversed by 11 non-domestic hoofstock . A combination naltrexone hydrochloride (30 mg/mg of A3080) and atipamezole hydrochloride (5 mg/mg of of KET and MED provided chemical MED) given intramuscularly. There was no mortality or morbidity associated with this immobilisation of impala ( protocol. Aepyceros melampus)3 and MED combined with M99 Key words: A3080, anaesthesia, atipamezole hydrochloride, ketamine hydrochloride, provided adequate immobilisation of medetomidine hydrochloride, naltrexone hydrochloride, nyala, thiafentanil, Tragelaphus Arabian oryx for at least 3 h1. KET has a angasi. synergistic effect when combined with Cooper D V, Grobler D, Bush M, Jessup D, Lance W Anaesthesia of nyala (Tragelaphus MED3,11 and is observed to potentiate the angasi) with a combination of thiafentanil (A3080), medetomidine and ketamine. Journal sedative effect of synthetic opioids16. of the South African Veterinary Association (2005) 76(1): 18–21 (En.). Conservation and A potent and selective "2 adrenoreceptor Research Center, Smithsonian National Zoological Park, 1500 Remount Road, Front Royal antagonist, atipamezole hydrochloride Virginia, VA 22630, USA. (atipamezole) is highly effective in revers- ing sedation/anaesthesia induced by MED or MED/KET combinations in some 11,19 INTRODUCTION allow for individual selection of animals species , but other species such as Nyala (Tragelaphus angasi) are popular (e.g. trophy bulls). Reliable anaesthesia impala show re-sedation from MED 3 and economically important species of nyala has been difficult as shown by following atipamezole . stocked on many South African game previous reports that nyala are difficult to A pilot study was conducted on 5 farms and a flagship species in selected reliably anaesthetise and exhibit high boma-confined nyala (4 females and 1 national parks. They prefer a habitat of levels of stress-related morbidity and male) weighing 48±7kg(average ± SD) dense bush, which leads to complications mortality9 (DVC and DG, pers. obs., 2004). using a combination of A3080 (44 ± when field anaesthetic protocols with Thiafentanil (A3080) is a synthetic 14 µg/kg) and 200 mg of ketamine hydro- long induction times are used. Nyala are fentanyl derivative with a rapid, pro- chloride (KET)/animal (4.3 ± 0.6 mg/kg). fairly delicate antelope with thin skin and nounced opioid agonist activity. It has a This combination resulted in initial signs are predisposed to stress and capture shorter duration of action than carfentanil in 1:15 (min:sec) with recumbency in 4 of myopathy6,7,14. Traditionally, nyala are citrate (carfentanil) or etorphine hydro- 5 animals at 3:36 ± 2:18 min. The nyala captured by a net method2,7 and given a chloride (M99) and is only slightly less receiving the lowest dose of A3080 tranquiliser as rapidly as possible to pre- potent than carfentanil12,15,17,18. A3080 (24 µg/kg) did not become recumbent, but vent stress and myopathy6,7. There is a given at doses approximately 3.75 and 7.5 was easily caught. The induction time need to develop a rapid and safe field times greater than carfentanil produced did not decrease as the dose of A3080 anaesthesia protocol for nyala applicable more rapid immobilisation in elk15. A3080 increased. The quality of anaesthesia was for remote delivery of drugs, which would has a shorter induction time that carfentanil judged to be poor due to excessive strug- 16 13 aEzemvelo Kwa-Zulu Natal Wildlife, Private Bag X01, by 26–65 % in cervids . In impala and gling with difficulty of restraint, which St Lucia, 3936 South Africa. elk18 the induction time of A3080 was dose limited collection of physiological data. bSouth African National Parks, Kruger Park, South Africa. The animals had elevated respiration Present address: Catchco Africa, Highlands North, 2037 dependent. Naltrexone hydrochloride South Africa. (naltrexone) produces rapid and complete (31 ± 8/min), tachycardia (245 ± 22/min) cConservation and Research Center, Smithsonian Na- reversal of A3080 with no re-narcoti- and elevated rectal temperature (39.6 ± tional Zoological Park, 1500 Remount Road, Front Royal 13,17,18 Virginia, VA 22630, USA. sation . 0.5 °C) with good haemoglobin oxygen dInternational Wildlife Veterinary Services, 1451 Shaffer Medetomidine hydrochloride (MED) is saturation (91 ± 5 %). Owing to poor Rd., Santa Cruz, CA 95060. an imidazole-based compound with quality of the anaesthesia and the concern eWildlife Pharmaceutical Inc., Fort Collins, Colorado 80524, USA. potent selective and highly specific ago- for the welfare of the animal, naltrexone *Author for correspondence: [email protected] nistic activity at both pre and post-synap- (30 mg/mg of A3080) was given intramus- 2 19,20 2 Received: August 2004. Accepted: November 2004. tic " adrenoreceptors . It has an " cularly (i.m.) to end the procedure within

18 0038-2809 Tydskr.S.Afr.vet.Ver. (2005) 76(1): 18–21 10 min of induction. The animals stood in Table 1: Mean ± SD dosage rates and response times in nyala anaesthetised with A3080/ 1:15 ± 0:21 min and rapidly returned MED/KETM. towards normal. Group 1 Group 2 The objective of this study was to deter- mine if the rapid induction attribute of n 19 ± 9 ± A3080 could be combined with the potent Weight (kg) 62 ± 25 106 ± 26 2 selective " effects of MED plus the syner- A3080 (µg/kg) 45 ± 8 43 ± 3 16 gism of KET with opoids and MED to MED (µg/kg) 69 ± 19 63 ± 9 produce a rapid-acting, balanced combi- KET (µg/kg) 3.7 ± 1.0 2.0 ± 0.7 nation applicable to remote drug delivery Initial signs (min) 1:22 ± 0:21 1:48 ± 0:18 in this species’ dense habitat. The anaes- Recumbency (min) 3:11 ± 1:09 4:28 ± 1:48 thesia should be rapidly and completely NAL (mg/kg) 1.8 ± 0.7 1.3 ± 0.1 reversible. Previous reports of this combi- ATP (µg/kg) 340 ± 100 310 ± 50 Up (min) 2:28 ± 0:42 ** nation have been successful in producing rapid, safe and completely reversible **These nyala were given tranquilisers and crated; therefore the ‘Up time’ was compromised. anaesthesia in Lichtenstein's hartebeest (Sigmoceros lichtensteinil)5, roan antelope Group 2 consisted of free-ranging Animal Health, Exton, PA) at a dosage of (Hippotragus equines)4 and gemsbok (Oryx animals darted from a vehicle at a range of 5 mg/mg of MED. The time to stand- gazelle)10. 25–40 m. The 5 adult (trophy) males ing and completeness of recovery were (approximately 120 kg) received A3080 recorded. The anaesthetised free-ranging MATERIALS AND METHODS (5 mg) plus MED (7 mg) and 200 mg of nyala were crated and given tranquilisers The study was conducted with boma- KET/animal. The 2 adult female (approxi- [150 mg perphenazine enanthate (Trilifon habituated and free-ranging nyala. The mately 60 kg) received A3080 (2.5 or 3 mg), Enanthate, Schering-Plough, Isando, Kwa-Zulu Natal Nature Conservation MED (4.5 or 5 mg), respectively, plus South Africa) i.m. plus 15 mg haloperi- Service captured the animals using physi- 200 mg of KET/animal. Following moni- dol (Haloperidol®, Kyron Laboratories, cal methods routine in the management toring these animals were placed in crates Johannesburg) intravenously (i.v.)] at the of this species in the Hluhluwe Umfolozi and transported to holding bomas. time of the naltrexone and atipamezole Park. The animals included both sub- Data collected included the interval injections. This is the standard protocol of adult and adult males and females that from injection to 1st signs of drug effect the Natal Parks Board Game Capture Unit were conditioned to the bomas for at least and the time the animal became recum- when placing field captured nyala into a 3 weeks prior to the study. The diet bent. In Group 1 initial physiological data boma, therefore the full extent of recovery consisted of lucerne hay and commercial collection (Initial Time) began in the boma from the naltrexone and atipamezole antelope cubes and freshly cut browse. after the animal became recumbent could not be evaluated completely in this Water was available ad-libitum. To mimic (2:30 ± 0:50 min) and could be approached group. field conditions, food and water was not and safely handled. The ‘Time 0’ was after withheld prior to the anaesthesia. Their the animal was removed from the boma, RESULTS body condition and pelage was rated weighed and placed in sternal recumbency Group 1 received a combination of good by local biologists. at a central location for data collection A3080, MED and KET and showed signs The bomas were approximately 5×4m (5:45 ± 1:25 min). The data collection for at 1:22 ± 0:21 min with recumbency at with walls constructed with closely animals in Group 2 began once the animal 3:11 ± 1:09 min (Table 1). Neither the spaced4×13cmwide wooden boards. A was moved to the site of the transport onset or down time was related to the solid roof (2 m in height) covered the crate (n = 2) (Time 0). This was 3:30 and dosage of A3080 or MED. The quality of boma. The floors were rough-finished 1:20 min, respectively, after the animal the anaesthesia was good to excellent concrete covered with a layer of river sand. was down and stable. In the other 7 nyala depending on the degree of muscle relax- The study group consisted of 7 males and basic monitoring started once the animal ation and ease of handling. The improved 12 females housed in bomas and 9 free- was down and stable (lapse time was quality of the anaesthesia and muscle ranging adults (2 females and 7 males). 1:40 ± 0:50 min). relaxation was correlated to the increas- Anaesthetics were A3080 (A3080, Wild- In Group 1 the physiological parame- ing dosage of MED rather than an increas- life Pharmaceuticals, White River, South ters [heart rate, respiration rate, pulse ing dose of A3080. Africa), 10 mg/ml, MED (Medetomidine, oximetry (Nellcor N 200, Nellcor Incorp., The physiological data from Group 1 Wildlife Pharmaceuticals, White River), Haywood, CA 94588, USA), and rectal (Table 2) shows acceptable heart and res- 20 mg/ml and KET (Ketamine 200, Wild- temperature] and the animals' responses piration rates with the higher rates for life Pharmaceuticals, White River), and muscle relaxation were evaluated and both recorded initially when the animal 200 mg/ml. These were all formulated as recorded. The data collected in Group 2 in- became recumbent and in animals receiv- sterile injectable solutions in multidose cluded initial signs, down time, heart rate, ing the lower dosages of either A3080 or vials. The delivery system was a CO2- respiration rate, rectal temperature and MED. The average haemoglobin oxygen powered remote injection device deliver- muscle relaxation. Pulse oximetry read- saturation ranged from 80 to 86 %, with inga3mlair-pressurised plastic dart with ings were limited to 2 animals, a complete the lower values seen at initial recumbency, a 40 mm collared needle (Dan-Inject, 15 min monitoring in 1 male and a 15 min while 15 min later the value improved. South Africa) to insure a deep i.m. injec- reading in a 2nd male. The average initial rectal temperature tion. The A3080 was reversed using i.m. was 39.6 °C and only rose to 39.8 °C by the Group 1 consisted of 19 boma-confined naltrexone (Trexonil®, naltrexone HCl, end of the monitoring period. An area of male and females weighing 62 ± 25 kg Wildlife Laboratories, Fort Collins, CO) at piloerection of 4–8 cm was noted in that received A3080 (45 ± 8 µg/kg), MED a dosage of 30 mg/mg of A3080. The MED 12 animals around the dart site prior to (69 ± 19 µg/kg) plus KET (200 mg/animal was reversed using i.m. atipamezole recumbency. Eight females and 2 males [3.7 ± 1.0 mg/kg]). (Antisedan®, atipamezole HCl, Pfizer exhibited pelvic thrusting prior to recum-

0038-2809 Jl S.Afr.vet.Ass. (2005) 76(1): 18–21 19 Table 2: Physiological data of nyala anaesthetised with A3080/MED/KET including respira- 1:30 min of darting making physical tion rate, heart rate, oxygen saturation and body temperature. Mean ± SD. capture easy; in addition the distance travelled after darting was short with Group 1 Group 2 appropriate dosages, which proved to be an advantage in the Group 2 free-ranging n 19 ± 9 ± Respiration rate animals. Initial 24 ± 10 The physiological parameters measured 0 time 14 ± 6 24 ± 5 during this study were maintained within 5 min 15 ± 7 16 ± 8 an acceptable range with the exception of 10 min 13 ± 5 19 ± 1 initial hypoxia, which improved over the 15 min 15 ± 4 18 ± 2 monitoring period. All animals exhibited Heart rate an initial increased respiration and heart Initial 144 ± 46 rate, which over the next 15 min slowed to 0 time 106 ± 45 81 ± 11 an acceptable rate. 5 min 95 ± 32 68 ± 5 10 min 91 ± 15 67 ± 10 The piloerection at the dart site was 15 min 90 ± 13 69 ± 3 seen in 12 animals and was attributed to MED as reported in impala3. The pilo- O2 saturation 5 min 80 ± 16 72* erection is useful in a field situation to 10 min 82 ± 11 80* help follow the animal if the dart falls out. 15 min 86 ± 8 86** The cause of the pelvic thrusting is not Temperature (C) fully understood, but surprisingly was Initial 39.6 ± 0.5 39.1 ± 0.46 observed more commonly in females (10 End 39.8 ± 0.7 39.3 ± 0.52 of 14) compared with males (2 of 14).

**Only 1 reading was obtained on 1 animal for this period. The antagonists (naltrexone and atipa- **Average of readings on 2 animals for this period. mezole) were given i.m. and resulted in a controlled, rapid and complete reversal. bency. The quality of the anaesthesia was tranquilisers and placed in crates. Their When these drugs were given i.v. in other good in all but one male receiving a lower recovery was rapid to the point where species the reversal was very rapid and than average dosage of both A3080 they were sternal with control of their the animals had a tendency to stumble or (37 µg/kg) and MED (55 µg/kg). heads within 2–4 min, but they remained crash into fixed objects3. The Group 2 free-ranging nyala were quiet in the crate and eventually stood in darted by vehicle at ranges of up to 40 m. 10–20 min, which is desirable for crated REFERENCES Five of the 9 animals showed 1st signs at animals. 1. Ancrenaz M S, Ostrowski S, Anagariyah S, 1:48 ± 0:18 min with recumbency at Delhomme A 1996 Long-duration anesthe- 4:28 ± 1:48 min. The other 4 briefly disap- DISCUSSION sia in Arabian oryx (Oryx leucoryx) using a peared into the dense bush, which pre- Ketamine at 200 mg/animal was a medetomidine-etorphine combination. cluded obtaining initial signs and time of constant throughout this study. This Journal of Zoo and Wildlife Medicine 27: recumbency, but all were found recumbent dosage was selected since this volume 209–216 2. Burroughs R E J 1993 Chemical capture of in an average of 11 min. The estimated filled the 3 ml dart and was beneficial in antelope. In Mckenzie A A (ed.) The capture 4,5,10 distance travelled by all Group 2 nyala previous studies . and care manual. Wildlife Decision Support after darting was less than 40 m. Pelvic Ketamine has synergistic properties Services, Pretoria, and the South African thrusting was observed in both females. with both MED3,11 and opiates16 which Veterinary Foundation, Pretoria: 366–367 Data from Group 2 was comparable to decrease the dosages of MED and A3080 3. Bush M, Raath J P, Phillips L G, Lance W 2004 Immobilisation of impala (Aepyceros the boma-confined nyala with the excep- and gains the dissociative properties of melampus) with a ketamine hydrochlo- tion of slower heart rates (Table 2). Two KET to assist in the rapid down time. This ride/medetomidine hydrochloride combi- male nyala had more complete physiologi- dosage of KET was not observed to cause nation, and reversal with atipamezole cal data sets, and 7 only heart rate, respira- a residual problem following the reversal hydrochloride. Journal of the South African tion and body temperature collected of A3080 and MED. Veterinary Association 75: 14–18 4. Citino S B, Bush M, Grobler D, Lance W twice. The anaesthesia was good in all In the pilot study using only A3080 and 2001 Anaesthesia of roan antelope (Hippo- animals with good muscle relaxation, KET, there was a rapid onset and down tragus equinus) with a combination of which facilitated handling and crating. time, but the quality of the anaesthesia A3080, medetomidine and ketamine. Jour- The recoveries of the nyala in both was poor due to the muscle rigidity and nal of the South African Veterinary Association groups were comparable. Following excessive struggling. To decrease the 72: 29–32 5. Citino S B, Bush M, Grobler D, Lance W the i.m. injection of naltrexone and rigidity induced by the opiate, A3080, a 2002 Anesthesia of boma-captured Lichten- 2 atipamezole the average time to standing powerful rapid-acting " agonist (MED) stein's Hartebeest (Sigmoceros lichtensteinii) in Group 1 was 2:28 ± 0:42 min. The was added to Groups 1 and 2. This with a combination of thiafentanil. medeto- recovery progressed rapidly with the combination also produced a rapid onset midine, and ketamine. Journal of Wildlife animals appearing to be 90 % recovered and recumbency, plus having an animal Diseases 38: 457–462 6. Dolensek L S, Herron A J, Stover J, Doherty within 8–10 min. The recovery was that was relaxed and manageable. The J G 1982 Myopathy in the nyala. Journal of smooth with the animal first gaining addition of MED resulted in a lower American Veterinary Medical Association 18: control of its head and maintaining a haemoglobin oxygen saturation, but the 1232–1236 sternal position until standing in a con- benefits of the relaxation outweighed the 7. Ebedes H, Raath J P 1999 Artiodactylids: use trolled manner. Most nyala regained their decreased haemoglobin oxygen satura- of tranquilizers in wild herbivores. In Fowler M E, Miller R E (eds) Zoo and wildlife feet on the 1st attempt. The exceptions tion. With the A3080/MED/KET combina- medicine: current therapy 4. W B Saunders, were the field-anaesthetised nyala in tion it was observed that nyala were Philadelphia: 575–585 Group 2, which received i.v. and i.m. oblivious to their surroundings within 8. Greth A, Vassart M, Anagariyah S 1993

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