Respiratory Depression in Impala During Chemical Immobilization
The impala (Aepyceros melampus) is the most widespread antelope of the savannas of eastern and southern Africa and the bushveld of South Africa.1 It is a medium-sized antelope with slender, well-developed legs and a long neck. The impala stands 28–36 inches high and weighs 88–167 pounds. Impala males are approximately 20% heavier than females and have wide, winding horns that are 18–36 inches or longer.2 Like other antelope, the impala is a member of the family Bovidae, and the only member of the subfamily (or tribe) Aepycerotini.1
Both impala males and females have a tan coat with a reddish-brown saddle and white markings at the eyes, the inside of the ears, throat, the underside of the torso and tail. They also have black markings at the ears, tail and back feet. The darker, black-faced impala (Aepyceros melampus petersi) of southwest Africa is a less common subspecies.1
Like a few other African antelope species, the impala is considered an “edge” species that favors areas between woodland and grassland. It is a mixed feeder that eats grass during the rainy season and switches to browsing during the dry season.1,2 Impala are often seen in large breeding herds that are closely attended by a dominant male. It is a seasonal breeder that mates during the rainy season and given birth six months later. During the rut, large herds of up to 100 impalas enhance male sexual competition.1 Near the end of gestation, females leave the herds and seek secluded places to bear their fawns.
Chemical Immobilization and Stress
Chemical immobilization has become the chief method of capture for large wildlife species for the purposes of translocation, diagnostic testing and medical treatment. In zoos, farms, breeding facilities and even in free-ranging situations, chemical immobilization is usually carried out from the ground. Under field conditions, wild animals often have to be located and darted from a ground-based vehicle or helicopter.3 All of the above methods of capture cause significant stress and trauma to these animals, potentially giving rise to complications.
Remote drug delivery systems are used for the purpose of administering immobilizing drugs, usually via a dart gun or blowpipe. Drugs are injected by means of a dart syringe which is fired from the dart gun or blowpipe at a distance. Since dart volume can be a limiting factor, immobilizing drugs must be highly potent and concentrated. They must also have a high therapeutic index and wide safety margin, since animals generally cannot be examined and weighed prior to immobilization.3 The ideal immobilizing drugs must also be fast-acting to limit stress and the likelihood of escape following darting. They should also be reversible since animals are often released back into the wild immediately after the procedures are performed.
Respiratory Depression as a Complication
The chemical immobilization of impala and other wildlife is associated with risks. In most cases, animals cannot be examined with regard to their weight and health status beforehand; further, they usually cannot receive adequate supportive treatment during immobilization in the field. Finally, they are often highly-stressed and sometimes run long distances before the immobilizing drugs take full effect. Most drugs used for immobilization have side effects; they not only cause sedation by influencing the central nervous system, but also influence cardiovascular, respiratory and thermoregulatory functions.3 Complications commonly encountered during wildlife immobilization include respiratory depression, cardiovascular disturbances, bloat, impaired thermoregulation, hypoxia and capture myopathy.3-5
Potent opioids are often components in the drug formulations used to immobilize impala. One chief disadvantage of opioids is that they can cause clinically significant respiratory depression. This is due to their strong effect on mu-opioid receptors.5 Activation of mu-opioid receptors in the respiratory centers of animals depresses neurons that generate the normal respiratory rhythm. At the same time, activation of these receptors activate other receptors in the brain stem, on the aortic arch and carotid bodies, which depresses normal respiratory function.4 Alpha-2 agonists such as guanabenz, clonidine, medetomidine, and dexmedetomidine cause reflex bradycardia and hypotension, which can lead to hypoxemia and tissue hypoxia. Hypoxia can give rise to capture myopathy, which can ultimately lead to cardiac arrest and death.3
Treating Respiratory Depression in Impala
There are several approaches available to lessen opioid-induced respiratory depression in impala undergoing chemical immobilization. Assisted ventilation and oxygen insufflation can combat hypoxia,3 while agents such as opioid antagonists or partial antagonists can be used. The latter also reduces desirable effects however, such as the degree of immobilization, sedation and analgesia. Respiration can also be improved during chemical immobilization events via respiratory stimulants which act on non-opioid receptor systems such as serotonin receptor agonists, potassium channel blockers and ampakines.6
The use of oxygen is recommended during wildlife immobilization; this can be combined with a partial opioid reversal to better alleviate hypoxia.3 Naltrexone is frequently used to fully reverse opioid-based immobilization after capture; this is especially useful if the animal needs to be released back into the field and must be fully alert. If analgesic or sedative effects are still required, partial opioid antagonists or mixed agonists/antagonists may be used for the reversal of opioids such as diprenorphine, nalorphine or butorphanol.4,5 Increased respiratory depth followed by ear twitching, eye movement and lifting of the head are signs of recovery after naltrexone administration.3
Partial mu-receptor antagonists such as butorphanol can be used to alleviate respiratory depression caused by strong mu-agonistic immobilization drugs.3,5 Some of these partial antagonists, however, also reduce the immobilization effects of opioids. Potassium channel blockers such as doxapram can also be used to stimulate breathing. Doxapram has been shown to increase the minute ventilation in large herbivores immobilized with etorphine.3 It should be noted that the respiratory effects of doxapram are usually short-lived.
While efficacious drug combinations used for darting were not always commercially available as pre-mixed solutions, many of these can now be purchased as highly-concentrated drug formulations for this purpose from compounding pharmacies. These formulations are often species-specific, reliable and are less likely to bring about complications such as respiratory depression in impala than drugs and combinations used in the past.
3Arnemo, J. Kreeger, T. (2018). Handbook of Wildlife Chemical Immobilization 5th Ed. Sunquest Publishing, 2007.
4Arnemo, J., et. al. Field Emergencies and Complications. In: G. West, D. Heard, & N. Caulkett, eds. Zoo Animal and Wildlife Immobilization and Anaesthesia. Oxford: Wiley Blackwell, pp. 139–147.
5Bailey, P.L., et. al. (1985) The ED50 of carfentanil for elk immobilization with and without the Tranquilizer R51703. The Journal of Wildlife Management, 49(4), pp.931–934.
6Van der Schier, R., et. al. (2014) Opioid-induced respiratory depression: reversal by non-opioid drugs. F1000 Prime Reports, 6, pp.1–8.
About NexGen Pharmaceuticals
NexGen Pharmaceuticals is an industry-leading veterinary compounding pharmacy, offering sterile and non-sterile compounding services nationwide. Unlike other veterinary compounding pharmacies, NexGen focuses on drugs that are difficult to find or are no longer available due to manufacturer discontinuance or have yet to be offered commercially for veterinary applications, but which still serve a critical need for our customers. We also specialize in wildlife pharmaceuticals, including sedatives and their antagonists, offering many unique options to serve a wide array of zoo animal and wildlife immobilization and anesthesia requirements.
Our pharmacists are also encouraged to develop strong working relationships with our veterinarians in order to better care for veterinary patients. Such relationships foster an ever-increasing knowledge base upon which pharmacists and veterinarians can draw, making both significantly more effective in their professional roles.
Disclaimer
The information contained in this blog post is general in nature and is intended for use as an informational aid. It does not cover all possible uses, actions, precautions, side effects, or interactions of the medications shown, nor is the information intended as medical advice or diagnosis for individual health problems or for making an evaluation as to the risks and benefits of using a particular medication. You should consult your veterinarian about diagnosis and treatment of any health problems. Information and statements have not been evaluated by the Food and Drug Administration ("FDA"), nor has the FDA approved the medications to diagnose, cure or prevent disease. Medications compounded by NexGen Pharmaceuticals are prepared at the direction of a veterinarian. NexGen Pharmaceuticals compounded veterinary preparations are not intended for use in food and food-producing animals.
NexGen Pharmaceuticals, LLC does not recommend, endorse or make any representation about the efficacy, appropriateness or suitability of any specific dosing, products, procedures, treatments, services, opinions, veterinary care providers or other information that may be contained in this blog post. NEXGEN PHARMACEUTICALS, LLC IS NOT RESPONSIBLE NOR LIABLE FOR ANY ADVICE, COURSE OF TREATMENT, DIAGNOSIS OR ANY OTHER INFORMATION, SERVICES OR PRODUCTS THAT YOU OBTAIN THROUGH THIS BLOG POST.