Tolazoline as a Reversal Agent for Wildlife and Exotic Animals
Field anesthesia is often necessary for both invasive and noninvasive procedures on wild animals. For invasive procedures, the potential for immediate and lasting pain must be addressed and appropriate analgesia provided. In situations where the minimum standard of safe anesthesia and effective analgesia cannot be provided, the investigator and governing bodies should rigorously evaluate the risk to patients against the value of the data obtained.Wild animals are used for research and management purposes throughout the world. Animals are often subjected to similar procedures, which can involve risks from capture, anesthesia, handling, sampling, marking, and sometimes selective removal.For these reasons, anesthetic protocols for wildlife should be as efficient as possible, providing effective anesthesia, analgesia and anesthetic reversal.
Anesthesia is an integral part of veterinary and zoological medicine. Even basic clinical examinationscan require sedation or anesthesia, as most patients are either too timid, too fast, or too dangerous to examine without chemical immobilization.1 Most drugs and procedures pertaining to wild and exotic animal medicine are well known from domestic animal or human medicine, but new combinations and modifications to existing protocols and equipment are common.
Anesthesia in the Field
Before attempting to anesthetize an unfamiliar species, the veterinarian or wildlife managershould consider and review any anatomic or physiologic adaptations that might influence the anesthetic event. Then, the level of anesthesia required for the procedure planned should be considered. The vast majority of procedures performed in field or zoo settings involve loading, crating, or simple clinical exams; for these, a much lighter level of anesthesia may be used than for a surgical procedure.1 Similarly, the likely duration of the procedure and the need for and possibility of prolonging the anesthesia should be considered. Pre-planning is important, particularly with large, heavy animals, and sufficient crates, ropes, machinery, and manpower should be readily available, as should all equipment needed for the procedure as to not prolong down time unnecessarily. An important part of planning is to inform all team members of what is going to happen and what is expected of them. It is also useful to discuss contingency plans ahead of time. Additional factors to consider are climatic conditions and the demeanor of the patient. It sometimes takes more courage and determination on the part of a veterinarian to call off a procedure because an animal is stressed or the weather is too hot than to attempt to executethe original plan.2
Field anesthetic equipment can involve several different layers. While small, sedentary animals may be handled and anesthetized without the use of complicated equipment, the majority of species do require some sort of specialized devices to allow safe and effective anesthesia.For therestraint of birds, reptiles, and small mammals, towels, hoop nets, and gauntlets are indispensible components.2 For larger animals, squeeze cages, narrow corridors, chutes and stockades may aid in restraint. In some cases (and with certain species), trapsmay aid in capturing shy, fragile or elusive animals.
Once physically restrained, many smaller animals may be induced using volatile anesthetics delivered using anesthetic machines. Chamber induction may be employed when handling of the animal is considered impractical, but in many cases, repurposed items (such as plastic bottles) can be used in lieu of custom-built masks.3
Remote injection systems (for sedating wild animals at a distance) are an integral part of field and zoological anesthesia.The simplest instruments of this type are homemade pole syringes, but versions both with and without spring loaded injection have beencommerciallyavailable for quite some time.Beyond a few meters, pole syringes are of no use, and darts are the preferred method of delivery.4While some wildlife managers and researchers have fashioned homemade versions of these, they tend to be inaccurate at longer distances and don’t have the reliability of commercially-manufactured darts. These are available from several manufactures, including Dan-Inject, Telinject and Pneu-dart. The first twoare multiple-use compressed air-driven darts, while the latter employs single-use darts injected through a powder charge.1
Xylazine: A Staple of Field Anesthesia
Xylazine was the first α2-agonist sedative to be widely used in veterinary medicine. It producesdose-dependent sedation and markedly decrease dose rates of other anesthetic agents administered subsequently.4Xylazine is the most frequently used drug for sedation in large animals. The initial demeanor of the animal greatly influences the sedation produced by a given dose of an α2-adrenergic agonist. The sedative effect of α2-adrenergic agonists can be overridden by elevated sympathetic tone, resulting in two characteristic features of α2-adrenergic agonist sedation.3 The sedative effect produced by lower doses of α2-adrenergic agonists is not as stable. Calm, quiet patients require smaller doses, whereas anxious or fractiousanimals typically require larger doses. The ideal dose can be difficult to predict, especially when recumbency is not desired.2Having an experienced wildlife veterinarian can make the necessary adjustments easier, but even seasoned practitioners are occasionally surprised.
Xylazine can be administered IV, intramuscularly (IM), or subcutaneously (SQ). Intravenous administration of α2-adrenergic agonists provides a faster onset and more intense level of chemical restraint and analgesia. The fairly rapid onset time can be used to advantage, allowing multiple smaller IV doses of an α2-adrenergic agonist to be administered in an attempt to titrate the effect to the desired level.2,4 Intramuscular administration results in a more gradual onset and provides a longer duration of less intense chemical restraint and analgesia. IM administration is often used when the animal’s demeanor does not allow IV administration or when extended duration is desired. The intramuscular dose is traditionally twice the IV dose one would select for the patient based on the desired level of effect and the patient's initial demeanor.4 SQ administration results in the most gradual onset, longest duration, and mildest peak effect. Administering the IV dose IM or SQ is a method used to produce a degree of sedation with limited the risk for recumbency.α2-Adrenergic agonists such as xylazine produce dose-dependent side effects, including decreases in gastrointestinal motility and cardiorespiratory function.2
Xylazine should be avoided or used cautiously in compromised patients and should be reversed on completion of the procedure.1 Even in normal, healthy animals, when large doses of α2-adrenergic agonists are administered (e.g., to produce recumbency), reversal is advisable to minimize the risk for gastrointestinal complications. Restraint or interaction should be minimized whenever possible until xylazine has produced a reasonable degree of patient control.Unless contraindicated, stressed or fractious animals should be sedated with xylazine 5 to 10 minutes before the anesthetic induction sequence.
Tolazoline as a Reversal Agent for Xylazine
Tolazoline HClbelongs to the synthetic group of α-adrenergic blocking agents known as the imidazoline derivatives. It has been approved by the U.S. Food and Drug Administration (FDA) and indicated for the reversal of effects associated with xylazine in horses. It also will reverse the analgesic effects of α-agonists. Tolazoline antagonizes the effects of detomidine more completely, hastens recovery, and lasts longer than atipamezole.4
Tolazoline is a vasodilator that has direct actions on blood vessels and also increases cardiac output. It can interact to some degree with histamine, adrenergic, and cholinergic receptors, but the mechanisms of its therapeutic effects are not clear. Tolazoline’s mechanism of action is by means of a direct effect on peripheral vascular smooth muscle and indirect effects produced, in part, by release of endogenous histamine. It has moderate α-adrenergic blocking activity and has histamine agonist activity. Tolazoline usually reduces pulmonary arterial pressure and vascular resistance. In humans, it is used in treatment of persistent pulmonary hypertension of the newborn.5
In wildlife medicine, tolazoline is often used to reverse sedation and cardiovascular effects of xylazine. Tolazoline is fast-acting (usually within 5 minutes of IV administration), but may not fully reverse effects on sedation or heart rate and rhythm. Its duration of action is relatively short, occasionally requiring repeat doses.4,5 In horses that received detomidine(0.04 mg/kg sublingual) then tolazoline (4 mg/kg IV) 1 hour later, tolazoline’s effect on detomidine-induced changes in chin-to-ground distance were minimal; detomidine-induced changes in heart rate and rhythm only persisted for 15 to 20 minutes.4
1Chinnadurai, S., et. al. Best-Practice Guidelines For Field-Based Surgery And Anesthesia Of Free-Ranging Wildlife. I. Anesthesia And Analgesia, Journal of Wildlife Diseases, 52(2s), (1 April 2016).
2Sikes, R.S., Paul, E. Fundamental differences between wildlife and biomedical research. Ilar J. (2013) 54:5–13.
3Giroux, Marie-Chantal et al. Anesthetic and pathological changes following high doses of ketamine and xylazine in Sprague Dawley rats. Experimental animals vol. 64,3 (2015): 253-60. doi:10.1538/expanim.14-0088
4Kreeger TJ, Arnemo JM (eds): The Handbook of Wildlife Chemical Immobilization, 4th ed. Private publishing, 2012.
5Plumb’s Veterinary Drugs.
6Casbeer C, Knych HK. Pharmacokinetics and pharmacodynamic effects of tolazoline following intravenous administration to horses. Vet J. 2013;196(3):504-509.
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.
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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.
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