EVALUATION OF MEDETOMIDINE-KETAMINE AND MEDETOMIDINE-KETAMINE-BUTORPHANOL FOR THE FIELD ANESTHESIA OF FREE-RANGING DROMEDARY CAMELS (CAMELUS DROMEDARIUS) IN AUSTRALIA Open Access

Dromedary camels (Camelus dromedarius) were introduced into Australia as haulage animals between 1840 and 1907. With the advent of motorized transport in the 1920s, many camels were liberated and established significant feral populations (McKnight 1969). Feral populations remained largely unmanaged until recent research showed their population has grown considerably over the last 100 yr (Edwards et al. 2005). The feral population, now estimated at >300,000 animals, with a population growth rate of almost 10% per annum (Lapidge et al. 2010), occupies approximately 3.3 million km² of central and northwestern Australia (Pople and McLeod 2010; Saalfield and Edwards 2010; Spencer et al. 2012). While studies of their environmental impacts have been few, their growing population is considered to pose threats to environmental, cultural, and agricultural values (Edwards et al. 2010). Large invasive herbivores exert widespread negative impacts in Australia, and management efforts focus on reducing or maintaining their population densities (Edwards et al. 2004; Bradshaw et al. 2007).

Before effective population control methods can be implemented, it is important to understand the ecology of the target species (Reddiex et al. 2006). Telemetry studies are an effective method for understanding spatial ecology, a particularly important feature in variable arid environments (Ito et al. 2006; Lethbridge et al. 2010). One method employed to control camels is to use the “Judas” animal technique at low animal densities (Taylor and Katahira 1988; Campbell et al. 2005; Woolnough et al. 2006). The Judas technique is used to assist in the control of gregarious pest species (Woolnough et al. 2012) and involves the tracking of a telemetry-collared Judas individual to lead an aerial shooting team to the group. The collared individual is not culled and is left alive to join another group (Campbell et al. 2005; Woolnough et al. 2006, 2012).

For the attachment of telemetry devices to large wild herbivores, a safe, effective, and efficient capture method is required (Woolnough et al. 2012). Ground-based pursuit capture methods, used in the past for the capture of free-ranging camels (Grigg et al. 1995; Edwards et al. 2001), are increasingly seen as less acceptable from an animal welfare perspective, especially in environments where heat stress is likely (Berger et al. 2010). Chemical capture methods using helicopters to administer anesthetic drugs via remote injection offer a more humane, time-efficient approach for species inhabiting remote areas with sparse vegetation (e.g., Ballard et al. 1982; Woolnough et al. 2012).

An effective chemical capture regime has been described for free-ranging Bactrian camels (Camelus bactrianus; C. Walzer unpubl. data), but not for free-ranging dromedary camels. Sedation and general anesthesia regimes have only been described for domestic dromedary camels (e.g., Penshin et al. 1980; White et al. 1987; El-Maghraby and Al-Qudah 2005; Marzok and El-Khodery 2009; Al-Mubarak 2012). Most regimes have used the alpha-2 adrenergic receptor agonists, xylazine (Al-Mubarak et al. 2008), detomidine, or medetomidine, in combination with the dissociative anesthetic ketamine.

A combination of medetomidine and ketamine (MK) has proven highly successful for the anesthesia of a diverse range of captive wild animal species, including ungulates (Jalanka and Roeken 1990) and dromedary camels (T. de Marr unpubl. data 1998). Medetomidine, a highly specific alpha-2 adrenergic receptor agonist with sedative and analgesic properties and producing good muscle relaxation, is available in high concentrations and is reversible but produces side effects that include bradycardia, respiratory depression, and disruption of thermoregulation (Woolnough et al. 2012). Ketamine, a short-acting cyclohexamine dissociative anesthetic produces only mild cardiorespiratory depression, works synergistically with medetomidine, has a wide safety margin, can be concentrated, and has a short duration of action (Woolnough et al. 2012). Additionally, butorphanol tartrate, a μ-receptor antagonist and κ-receptor agonist (Branson and Cross 2001), has been combined with medetomidine and ketamine (MKB) in artiodactylids (Chittick et al. 2001) and New World camelids (Georoff et al. 2010) to reduce the dose of ketamine and thus minimize the residual effect of ketamine when reversal drugs, atipamezole and naltrexone, are given. Commonly, atipamezole, a potent alpha-2 antagonist, is used to reverse medetomidine at three to five times the dose of medetomidine (Jalanka and Roeken 1990), and naltrexone, an opiate receptor antagonist, is used to reverse butorphanol at two to three times the dose of butorphanol (Radcliffe et al. 2000).

We evaluated physiologic and anesthetic data from a case series of anesthetic procedures performed on free-ranging dromedary camels in Australia using remote intramuscular (IM) injection of MK and MKB. We describe safe and effective anesthetic dose ranges for free-ranging camels and identify future investigation requirements for further procedure optimization.

During 2008–11, we captured free-ranging dromedary camels (Camelus dromedarius) for ecological research or as Judas animals (Woolnough et al. 2012) during six field campaigns in areas of Western Australia and South Australia (Table 1). Ambient temperatures ranged from 20 to 35 C.

Camels were darted from 5–12 m from a Robinson® 44 (R44) helicopter (Robinson Helicopter, Torrance, California, USA) targeting the gluteal, hamstring, or quadriceps musculature. Six-milliliter or 7-mL darts, fitted with 20-gauge, 38-mm wire barbed needles (Type C dart, Pneu-dart, Inc.) were fired from a cartridge-fired Pneu-dart® gun (Models 389 and 193, Pneu-dart, Inc.) using green charges at power control position three. Darts were filled with either MK (medetomidine, 20 mg/mL or 40 mg/mL [Kyron Laboratories, Johannesburg, South Africa]; ketamine 1-g vials [Mavlab, Brisbane, Queensland, Australia]) or MKB (butorphanol as Torbugesic, 10 mg/mL [Zoetis Australia, West Ryde, New South Wales, Australia]). Medetomidine and/or butorphanol was used as a solvent to dissolve the dry ketamine. Initial dosages for MK and MKB were extrapolated from previous experience and from other ungulate species (Jalanka and Roeken 1990). Additional doses were administered by dart from the air or ground when the effect produced was not satisfactory. Subsequently, doses were adjusted to ensure camels became recumbent without the requirement for extra darts or until they became heavily sedated and stationary and could be roped down without risk to field staff. Mature, nonpregnant females and subadult males were targeted. Body weights were estimated visually before darting. Animals with estimated body weight >400 kg were classified as adult, and those <400 kg were classified as subadult.

After darting, the helicopter left the immediate vicinity to decrease excitation during the onset of sedation. Visual contact with the darted animal was always maintained. The helicopter returned once the camel became recumbent or stationary. Animals that showed no or little sedation after 15 min were darted a second time with partial or full doses. Time-to-induction was recorded in minutes.

When the camel was recumbent or standing still, a blindfold was applied. Stationary, standing, sedated animals were roped down by applying a lasso and running the rope around the animals' legs until they became unbalanced. Once recumbent, the animal was moved into sternal recumbency if necessary, and the dart was removed. One person ensured the animal stayed in sternal recumbency with its head raised to prevent regurgitation. Long-acting oxytetracycline (Alamycin LA 300, Norbrook, Tullamarine, Victoria, Australia) was administered at 20 mg/kg by deep IM injection to reduce secondary infection risk at the darting site. Recumbent camels were physically restrained by tying the forelegs together to prevent any attempts to stand.

Anesthetic monitoring consisted of recording oxygen saturation (SpO₂), heart rate (HR), respiratory rate (RR), rectal body temperature (RT), pulse strength, mucous membrane color, capillary refill time, and muscle tone. Heart rate was measured by auscultation, a pulse oximeter (Nellcor NPB-40 handheld pulse oximeter; Covidien, Mansfield, Massachusetts, USA) was attached to the camel's tongue, and body temperature was measured using a digital rectal thermometer. Under adverse field conditions including excessive dust, wind, and heat, blood gas analysis and blood pressure monitoring were not attempted. Time recumbent was recorded in minutes.

Once data were recorded and the satellite-tracking collar was attached, atipamezole (Antisedan, 5 mg/mL; Novartis, Sydney, New South Wales, Australia) was administered IM into the quadriceps, biceps, or triceps and, in some cases, intravenously (IV) as well into the left jugular vein. Atipamezole dose rates were extrapolated from recommended dose rates for related species (Jalanka and Roeken 1990) using 2–5 mg atipamezole per 1 mg of medetomidine. For MKB animals, additional naltrexone (Trexonil, 50 mg/mL; Wildlife Pharmaceuticals, White River, South Africa) was given IV based on 3 mg of naltrexone per 1 mg butorphanol.

Blindfolds were removed, and camels were released from physical restraint once reflexes had become strong and consistent and muscle tone returned. The animals were observed until they stood and walked in a coordinated fashion. Time-to-recovery was recorded in minutes. Animals were circled from a distance in the helicopter for 5 min after walking to ensure recovery was complete and uneventful. Within 24 hr, the location of the camel was checked using the satellite transmitter.

The induction was classified as successful when an animal receiving a single dart became recumbent and unconscious and remained nonresponsive with good muscle relaxation throughout the procedure, or was standing, stationary, and heavily sedated so that it could be roped down without risk and, when recumbent, remained nonresponsive and unconscious throughout the procedure with good muscle relaxation. For animals that had poor induction, it was not possible to assess if the induction was unsuccessful because of the anesthetic combination or the dose rate or because the drugs failed to be administered properly (e.g., malfunctioning dart, partial drug delivery, poor drug absorption). Because poor inductions could not be exclusively attributed to the anesthetic regime (i.e., the drug combination may not have been properly delivered), the efficacy of the two drug combinations or their dose rates could not be estimated as a proportion of successful inductions. Nonetheless, time-to-induction and time-to-recovery were compared between MK and MKB in successfully induced animals using survival analysis.

Kaplan-Meier survival curves for time-to-induction and time-to-recovery were constructed separately for animals successfully anesthetized with MK or MKB and compared using a log-rank test. Recumbent times were not compared because they depended on the time required to attach the satellite-tracking collar and not on the anesthetic regime. Unpaired t-tests without assumption of equal variance were used to compare the means of physiologic parameters in camels successfully anesthetized with MK and MKB. Collection, formatting, and basic descriptive statistics of data were conducted using MS Excel (Microsoft Pty, Redmond, Washington, USA). Inference statistics were performed using STATA v12.1 (Stata Corp LP, College Station, Texas, USA), and the tests were interpreted at the 5% level of significance.

We anesthetized and attached satellite-tracking collars to 76 camels (43 females, 33 males) during the six capture campaigns. Thirty-three camels were anesthetized using MK and 43 using MKB. All appeared healthy based on their behavior, field observations, body condition, and clinical examination. Six (18.2%) of 33 camels anesthetized with MK and 15 (34.9%) of 43 anesthetized with MKB experienced poor induction.

Summary statistics for demographics (age, sex), estimated dose rates, time-to-induction, time recumbent, time-to-recovery, and physiologic parameters for successful anesthetic procedures for MK and MKB regimes are presented in Table 2. Included in the table for comparison are data for animals where the induction was considered poor. Dose rates are presented as approximate estimations, given the inherent lack of precision of the visual assessment of animals' body weight. Among successfully anesthetized animals, the dose rates of medetomidine and ketamine for the MK combination were higher than for the MKB combination (Table 2).

Initial signs of camel sedation, in chronological order, included slowing down, detachment from the back of the train of camels, ataxia, and occasional hypermetria. The initial effects progressed to more pronounced ataxia and immobility with low head carriage, which commonly continued to recumbency. Animals would often fall on their side into lateral recumbency, but some would sit down in sternal recumbency. Those animals that lay in lateral recumbency were quickly positioned sternally. Of the 27 camels successfully anesthetized using MK, two were stationary, standing, and nonresponsive and were roped down without risk; of the 28 using MKB, four were stationary, standing, and nonresponsive and were roped down without risk.

Although the median time-to-induction was shorter in MKB (8.5 min) compared to MK (11 min) for successfully induced animals, their corresponding Kaplan-Meier survival curves did not differ significantly (Fig. 1; P = 0.129). No animals regurgitated or displayed apnea. Mucous membrane color was pale but still pink. Pulse strength was moderate with capillary refill times of 1–2 sec in all animals. Except rectal temperature, which was marginally higher in MK than in MKB successfully anesthetized animals (P = 0.05), all physiologic parameters (RR, HR, SO₂) were not clinically nor statistically different between the two anesthetic regimes (P = 0.597, 0.133, 0.678, respectively).

Soon after atipamezole or naltrexone was administered, respiratory rate and depth increased, the camel would shake, and muscle fasciculations were noted. The animal would then gain control of its head. At this point, the head cover was removed, and the assistant holding the head would move away. Occasionally, camels made an unsuccessful attempt to stand, but in most cases they stood on the first attempt. As the animal became more alert, it would shake and respond to staff and slowly walk away. All camels recovered uneventfully and were moving when the satellite-tracking signal was checked the following day. Median time-to-recovery was 1 min shorter in successfully anesthetized MK (5 min) than in MKB (6 min) camels, and the corresponding Kaplan-Meier survival curves differed significantly (Fig. 2; P = 0.022). For animals successfully anesthetized with MK, median time-to-recovery was 5 min (n = 17, range = 1–7) when given IM and IV and 4 min (n = 9, range = 2–32) when given IM only (P = 0.98). For animals successfully induced with MKB, median time to recovery was 6 min (n = 7, range = 3–15) when given IM and IV and 7 min (n = 19, range = 2–43) when given IM only (P = 0.09). No animals were injured during the procedure, and all survived.

This is the first report of field anesthesia for free-ranging dromedary camels. Empirical evidence collected during this case series showed that MK and MKB are safe and effective anesthetic regimes when administered by remote injection. Although the likelihood of poor induction appeared higher for MKB, it was not possible to rule out darting failure and ineffectively delivered anesthetic agents. Consequently, the efficacy of the anesthetic regimes (i.e., proportion of successfully induced animals) could not be estimated and compared. Regardless, poorly induced camels were darted with lower average dose rates of anesthetics (Table 2). Among the successfully anesthetized animals, the mean dose rates for medetomidine and ketamine were higher for animals successfully anesthetized with MK than MKB (Table 2). For a 600-kg animal, this equates to 132 mg of medetomidine and 1.5 g of ketamine for MK, and to 72 mg of medetomidine, 1.4 g of ketamine, plus 30 mg of butorphanol for MKB. The cost of these two regimes is similar, but the increased medetomidine dose in the MK regime required considerably more atipamezole reversal, increasing the cost of the MK anesthetic regime relative to MKB.

While these dosages produced safe, effective anesthesia, the medetomidine dosage in the MK group may have been greater than the minimum effective dose rate. Effective anesthesia may be potentially achieved at a lower dose rate of medetomidine even without butorphanol. Concentrated butorphanol (50 mg/mL) was not available in Australia at the time of the study. If available in the future, the potential for increased butorphanol dosages to effectively reduce the ketamine dose should be further investigated. Median time-to-induction was 2.5 min shorter in successfully anesthetized MKB camels compared to MK (not statistically significant), but this difference had only minor consequences in the field. No substantial clinical difference was observed among physiologic parameters between the MK and MKB successfully induced animals (Table 2). Median time-to-recovery was significantly shorter (by 1 min) in camels successfully induced with MK.

No anesthetized camels had adverse physiologic values. Observed heart rates (40–86) and respiratory rates (12–54) were higher in comparison to normal ranges reported from habituated, domesticated camels (38–60 and 9–16, respectively; Bosona et al. 2011). Alpha-2 receptor agonists commonly cause bradycardia, but this was not observed in our study. Exertion caused by helicopter pursuit (Woolnough et al. 2012) and the use of the sympathetic nervous system stimulant ketamine in the protocols may have negated these effects. The high doses of medetomidine used to produce effective anesthesia in combination with ketamine did not appear to adversely affect cardiac or respiratory performance. Rectal temperatures (36.6–41.1 C) also reached higher values compared to the reported reference range from habituated domesticated camels (36.6–38.9 C; Bosona et al. 2010), most likely due to exertion prior to anesthesia.

Regardless of the anesthetic combination, the dose rate of medetomidine used for successfully anesthetized camels in this study (0.06–0.30 mg/kg) was very high when compared to effective dose rates reported for habituated, domesticated camels in Kenya (0.05 mg/kg; T. de Marr et al. unpubl. data). The majority of studies using medetomidine and ketamine for wild animal anesthesia in a variety of species have used medetomidine dose rates in the range of 0.06–0.10 mg/kg (Jalanka and Roeken 1990). However, Woolnough et al. (2012) successfully used a high medetomidine dose rate of 0.14 mg/kg in helicopter-captured free-ranging feral donkeys (Equus asinus). High doses in this study in comparison to de Marr et al. (unpubl. data 1998) could be attributed to the wild nature of the animals and stress exerted during the helicopter chase, making them refractory to the effects of medetomidine. Furthermore, the degree of variability of drug dose rates can relate to the animal's health, state of hydration, and pre-anesthesia stress. Regardless of the anesthetic combination, a fair assessment of the efficacy of these field-based regimes delivered by helicopter darting is inherently challenging. Deep IM injection is essential to get the best possible absorption of drugs, and this is not always possible in the field, especially with the low degrees of precision associated with helicopter darting.

The potent opioid etorphine, in combination with butorphanol, tiletamine-zolazepam, and detomidine, was used successfully in wild Bactrian camels (C. Walzer unpubl. data). This alternative anesthetic regime was rejected because of the onerous legislative requirements when transferring these drugs across state borders. A butorphanol, azaperone, medetomidine (BAM) combination was successfully tested once in this study and deserves to be investigated as an alternative anesthetic regime.

Atipamezole, a potent alpha-2 antagonist, is used to reverse the effects of medetomidine. When de Marr et al. (unpubl. data 1998) successfully used atipamezole IV at the rate of 0.15 mg/kg (3 mg of atipamezole to 1 mg of medetomidine), animals stood within 2 min. While relatively cheap concentrated medetomidine is available, concentrated cheaper forms of atipamezole are not. To reduce the cost associated with the reversal, we sought to reduce the dose of atipamezole, to produce a quick, effective recovery to standing and walking. While the standard atipamezole dose of 2–5 mg per 1 mg of medetomidine is optimal, 1.6–1.8 mg of atipamezole to 1 mg of medetomidine was effective (n = 9), and when given one third IV and two thirds IM, all animals were walking within 7 min with no evidence of resedation, because all animals were seen to be tracking normally early the following day. Regardless of the induction combination, there was no evidence that atipamezole administered both IV and IM significantly impacted the median time-to-recovery in comparison to atipamezole administered IM alone.

In conclusion, the regimes of MK or MKB delivered by remote injection were safe, effective, humane combinations for the anesthesia of free-ranging dromedary camels in the rangelands of Australia. Further investigation is necessary to determine the optimal effective dose rate for both regimes and to compare their relative efficiency (cost, convenience, side effects, time to effect). Alternative regimes including potent opiates such as thiafentanil/etorphine or BAM should be investigated.

We thank the following for their help during the course of this project: Cate Creighton, Stephen Bent, Ken Rose, Rob Parr, Gary Martin, Andrew Longbottom, Michael Elliot, Neville McInerney, Stephen Wait, Nikki Anderson, Neil Burrows, Megan Harper, and Lindell Andrews. Thanks go to Viktor Molnar for reviewing this manuscript. This project was funded by the Bureau of Rural Sciences of the Australian government, the Rangelands Natural Resource Management Coordinating Group, the Kimberley Zone Control Authority, the West Australia Department of Agriculture and Food (DAFWA), and Primary Industries and Regions of South Australian under its Australian Pest Animal Management Program. Ecoknowledge and the School of Animal and Veterinary Sciences of the University of Adelaide also provided support. The DAFWA ethics committee and the South Australian wildlife ethics committee approved the projects.