Exotic Animal Sedation Reversal
General anaesthetics and/or sedatives can take a number of hours to wear off and in some cases can cause patients to appear drowsy for more than a day. General anesthetic in healthy animals pose little risk, however, morbidity due to anesthesia does occasionally occur. In animals, as in humans, severe hypoxic brain damage can decrease intelligence following general anesthesia.1
A more dramatic and obvious cause of postanesthetic morbidity in some animals is renal failure. Some geriatric animals (dogs in particular) suffer from some degree of interstitial nephritis and in such animals even mild renal hypoxia may prove fatal within a relatively short time.1 Many choices are available to help veterinarians craft anesthetic protocols to meet the demand of increased sophistication of diagnostic and surgical procedures.
Sedation is often preferred over general anesthesia for exotic animals by veterinarians, primarily for reasons of patient safety. Exotic animals in captivity (as pets or in a zoo setting) often have a substantial financial component attached to them; additionally, they can present with higher levels of stress than domesticated animals, or a species might be physically less robust than most domesticated animals.
Reversal medicines act as synthetic adrenergic antagonists to reverse the actions of anesthetic and sedative compounds such as medetomidine and dexmedetomidine, which are widely used for wildlife such as deer. They also act to block alpha-adrenergics to onset arousal.1
Reversal Agents Used for Exotic Animals
Atipamezole is labeled for use as a reversal agent for medetomidine and dexmedetomidine in order to reduce their sedative and analgesic effects.
Atipamezole competitively inhibits alpha-2 adrenergic receptors, thereby acting as a reversal agent for alpha-2 adrenergic agonists (eg, medetomidine). Net pharmacologic effects are to reduce sedation, decrease blood pressure, increase heart and respiratory rate, and reduce the analgesic effects of dexmedetomidine. Atipamezole does not completely reverse the sedative and bradycardic effects in horses when administered 1 hour after sublingual detomidine gel.4
Naltrexone (an opioid antagonist) is a reversal agent that is also useful in determining if adverse behaviors (eg, self-mutilating or tail-chasing) in dogs or cats have a significant endorphin component.
Due to its long duration of action (approximately twice that of naloxone), naltrexone is preferred in wildlife and zoo animals when potent opioids, such as carfentanil and thiafentanil are used.
Pharmacologically, naltrexone competitively binds to opiate receptors in the CNS, thereby preventing both endogenous opioids (eg, endorphins) and exogenously administered opioid agonists or agonist/antagonists from occupying the site.
Tolazoline is an alpha-adrenergic antagonist used primarily as a reversal agent for xylazine. FDA-approved, it is indicated for the reversal of effects associated with xylazine in horses. It also will reverse the analgesic effects of alpha-agonists. Tolazoline antagonizes the effects of detomidine more completely, hastens recovery, and lasts longer than atipamezole.5Tolazoline reverses the analgesic effects of xylazine as well as the sedative effects. If an animal has been given xylazine for its analgesic properties, reversal may result in return of normal pain perception.4
By directly relaxing vascular smooth muscle, tolazoline has peripheral vasodilating effects and decreases total peripheral resistance. Tolazoline also is a competitive alpha-1 and alpha-2 adrenergic blocking agent, thus explaining its mechanism for reversing the effects of xylazine. Tolazoline is rapid acting (usually within 5 minutes of IV administration), but may not fully reverse effects on sedation or heart rate and rhythm. It has a short duration of action; repeat doses may be required.5
In horses that received detomidine 0.04 mg/kg sublingual (SL) 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.6
1Lee, L., DVM. Canine and Feline Anesthesia. Veterinary Surgery I, VMED 7412.
3Talukder MH, et al. Antagonistic Effects of Atipamezole and Yohimbine on Xylazine-Induced Diuresis in Healthy Dogs. J Vet Med Sci. 2009;71(5):539-548.
4Di Pietro S, et al. Effects of a medetomidine-ketamine combination on Schirmer tear test I results of clinically normal cats. Am J Vet Res. 2016;77(3):310-314.
5Zeiler GE. A review of clinical approaches to antagonism of alpha(2)-adrenoreceptor agonists in the horse. Equine Veterinary Education. 2015;27(1):48-54.
6Knych HK, Stanley SD. Effects of three antagonists on selected pharmacodynamic effects of sublingually administered detomidine in the horse. Vet Anaesth Analg. 2014;41(1):36-47.
