Exotic Animal Sedation Reversals: Theory & Practice

While there are inherent risks to deep sedation over general anesthesia in veterinary medicine,¹ it is generally accepted that sedation carries less risks compared to general anesthesia in most cases. “While no clear statistics exist regarding the morbidity and mortality of sedative versus anesthetic protocols, we do have concerning data illustrating the danger of modern anesthesia.”^2,3 These potential hazards should prompt a judicious regard for all procedures that involve alterations of consciousness in animals.

Sedation can be used to facilitate management of aggressive animals, the completion of minor procedures and diagnostic imaging.⁴ “However, sedation may not be safer than general anesthesia in all cases (eg, brachycephalic patient with significant stertor/stridor), as is often presumed.”^5,6

While general anesthesia will be the preferred protocol for certain procedures, there are many circumstances in which the veterinarian will opt for sedation rather than general anesthesia, particularly when exotic species are considered. Much of this has to do with patient safety, since exotic species in the wild, in a zoo setting or as companion animals are sometimes presented under greater stress than traditional companion animals in a practice setting. “Sedation is aimed at facilitating completion of the procedure without causing undue stress to the patient or veterinary staff. Drugs should provide adequate calming, pain relief (if needed), and reduction in mobility appropriate to the procedure.”⁴

Since many drugs commonly used for the sedation of animals in a veterinary setting can lead to prolonged post-surgical lethargy, veterinarians typically rely on reversal medications, particularly in the case of exotic animals. In a zoo setting or in the field, it can be disadvantageous to leave an animal in a physically depressed condition when there is a high probability that it will encounter other animals (perhaps even predators in the field, if it is a prey species). For exotics that are companion animals, quick recovery is of equal concern to owners as with domesticated species.

Patient Recovery

Since the goal of employing reversal agents is to return the animal to homeostasis as rapidly as possible post-procedure, it is important to include non-pharmaceutical aspects of recovery as well.

• In general, body temperature must be maintained so as not to prolong the recovery, and lessen oxygen requirement by muscle tissues. Forced warm air blankets and circulating warm water blankets are very effective at maintaining body temperature, but other means may be used at the veterinarian’s discretion.
• Endotracheal tubes (if used) should remain in place until the animal regains at least a couple of strong swallowing reflex to protect the airway, and with return of strong muscle tones.
• If animals pre-treated with reversible agents, recovery can be expedited by reversing the drugs with specific antagonists. Atipamezole and naloxone are two primary examples and they are best used titrated to effect.3

Classes of Reversal Agents

Despite the advent of short and ultra-short acting drugs, an in-depth knowledge of the reversal agents used is a necessity for any anaesthesiologist. Reversal agents are defined as any drug used to reverse the effects of anaesthetics, narcotics or potentially toxic agents.⁷

The introduction of newer drugs such as dexmedetomidine necessitate the veterinarian’s ongoing education in the newer reversal agents.⁷ Typically, reversal agents fall into two categories:

• Receptor-specific antagonists
• Non-specific analeptic agents

Antagonists are defined as agents which have a high affinity for a receptor and no intrinsic activity. For example anticholinesterases, naloxone, flumazenil, etc. Analeptics are defined as stimulants (e.g., theophylline, doxapram, caffeine, etc.)⁷

Pani et. al. state that “Routine reversal of neuromuscular blockade is more common in the United States but is not used in the European countries. However, the risk of residual neuromuscular blockade makes it necessary to reverse NMBAs. [These] may be reversed either by increasing the concentration of acetylcholine in the synaptic junction or aid the elimination of the drug or its metabolism.”

Sedatives and Reversal Agents

There are popular reversal agents that are commonly used in veterinary medicine; these are typically class-specific (opioids, alpha-2 agonists, dissociatives) to the sedation agent being used.

Medetomidine is an alpha-2 agonist used as a sedative, premedicant/anesthesia adjunct and analgesic in dogs, cats, and other small animals. An alpha adrenergic receptor, medetomidine has an alpha-2:alpha-1 selectivity factor of 1620 and, when compared to xylazine, is reportedly 10 times more specific for alpha-2 receptors vs alpha-1 receptors. Dexmedetomidine is an alpha-2 agonist similar to medetomidine. The injectable formulation is used as a preanesthetic agent & for sedation & analgesia in dogs & cats. In cats, the injectable has been used in an extra-label manner as an emetic.

Atipamezole is typically used as a reversal agent for medetomidine and dexmedetomidine. A synthetic α2-adrenergic antagonist, atipamezole reverses the effects of these compounds and is widely used in small and large animal practices, as well as in exotics and wildlife applications, such as deer.

Butorphanol is an opioid agonist/antagonist used in a variety of species as an analgesic, premedication, antitussive, or antiemetic. It is listed as a reasonably effective analgesic for horses, and is also used in small animals.⁹

Naltrexone hydrochloride is an opioid receptor antagonist that is used in veterinary medicine to block receptors as a reversal agent for opiate agonists such as butorphanol. It is also used for the treatment of recurring, compulsive animal behavior disorders such as tail-chasing and self-mutilation such as acral lick dermatitis.⁸

Xylazine is one of the most commonly-used drugs in veterinary practices. It is FDA-approved for use in dogs, cats, horses, deer, and elk to produce a state of sedation with a shorter period of analgesia, and as a preanesthetic before local anesthesia; and as a preanesthetic before general anesthesia in dogs, cats and horses. Xylazine is often used in combination with other agents (eg, opioids, ketamine, guaifenesin) for inducing anesthesia or perioperative sedation and analgesia in horses.¹⁰

Tolazoline belongs to the synthetic group of alpha-adrenergic blocking agents known as the imidazoline derivatives. It is typically used as a xylazine reversing agent and antagonist for intravenous use in horses, with minimal adverse effects typically presenting. Onset of arousal is generally apparent within 5 minutes of tolazine administration, depending on the depth and duration of sedation.