Abstract

General anesthesia is used frequently in zoological companion animal medicine for purposes in addition to surgery. Indications include sample collection, diagnostic imaging, and minor therapeutics. General anesthesia carries a significantly higher risk than sedation alone. Newer drugs and drug combinations have been found extremely useful and generally safe for sedation in zoological companion animal patients, and they provide a viable alternative to general anesthesia. Use of sedation for minor procedures is further amplified when combined with local analgesia.

Introduction

Anesthesia is defined by the American Society of Anesthesiologists (ASA) as a pharmacologically induced reversible state of amnesia, analgesia, loss of responsiveness, and loss of skeletal muscle reflexes, or more simply “without sensation.”¹ In contrast, sedation is a “drug induced depression of consciousness during which patients cannot be easily aroused, but responds purposefully following repeated or painful stimulation.” The advantages of sedation primarily focus on ease of administration, patient safety, and in human medicine, on relative cost. A study comparing death rates in dogs, cats and rabbits indicated a 2.5 times higher death rate in anesthetized verses sedated patients; however, numbers of sedated patients were small and significance is uncertain.² While not yet scientifically demonstrated, it is hopeful that sedation can provide a safe, effective alternative in exotic species in cases where general anesthesia carries increased risk or is non-essential. Additionally, sedation can be an effective adjunct to physical restraint, a means to reduce stress in hospitalized patients, and potentially a method to reduce patient memory of unpleasant procedures.

Disadvantages of sedation can include incomplete elimination of patient movement, patient semi-awareness, and lack of analgesia. Other disadvantages include risks associated with use of the drugs themselves; however, these can be mitigated with careful drug selection and dosing, patient selection, and vigilant monitoring.

The American College of Veterinary Anesthetists (ACVA) has published recommendations for monitoring patients that are sedated without general anesthesia. For these patients, intermittent monitoring using similar parameters as for general anesthesia is recommended. If the patient is sedated to the point where protective airway reflexes are lost, monitoring should proceed as with a fully anesthetized patient (continuous monitoring). Supplemental oxygen, and endotracheal tube and materials to obtain vascular access should be readily available.

Drugs Used for Sedation

Many drugs and drug combinations have been evaluated specifically for sedation in humans, with significant focus on sedation of the critical patient. While anesthetic studies are relatively plentiful, only a few drugs have been investigated specifically for sedation in animal species, most commonly in traditional companion animal species. In general, dosages for sedation are lower than dosages of the same drugs when used for preanesthesia, induction or general anesthesia. In zoological companion animals, potential agents include ketamine, xylazine, medetomidine, midazolam, diazepam, and opioids (specifically butorphanol in birds), alfaxalone and others. In some zoological companion animal anesthetic studies, complete anesthesia is not achieved; therefore, results are better described as sedation.

Midazolam

Midazolam is a benzodiazepine sedative with no analgesic effects and is used with increasing frequency as an alternative to general anesthesia for a variety of procedures in human patients. Midazolam reduces anxiety and has been shown to produce amnesia in humans and some laboratory species.^3,4

Reports on the use of midazolam in zoological companion animal patients are scarce and focus mainly on use in combination with other drugs for anesthesia, but not specifically for sedation. The effects of midazolam can be reversed with flumazenil.

Opioids

Opioids are frequently combined with midazolam for sedation in humans, and this combination has been found useful in birds and mammals. The effects of some opioids can be reversed with naloxone.

Ketamine

Ketamine is a NMDA receptor antagonist used in combination with other drugs for sedation, and as part of induction and general anesthesia. At low doses, ketamine has a wide safety profile in many species and can be an effective addition to other agents for sedation in zoological companion mammals. Lower dosages are analgesic. Combinations described in humans and animals include ketamine/midazolam, ketamine/opioid and ketamine/dexmedetomidine. Suggested dosages for sedation in zoological companion mammals range from 5–10 mg/kg.

Dexmedetomidine

Dexmedetomidine is the newest agent for use for light sedation of critical human patients in the ICU and is believed to have a safety profile superior to benzodiazepines.⁵ Dexmedetomidine has also been evaluated and found to be effective alone and with the addition of other agents in cats.⁶ The author has used dexmedetomidine in combination with low-dose ketamine and an opioid, with or without the use of midazolam for preanesthesia and sedation in rabbits. Optimal dosages of dexmedetomidine for sedation in zoological companion patients are unknown. Effects of dexmedetomidine can be reversed with atipamezole.

Alfaxalone

Alfaxalone (Alfaxan, Jurox, NSW, Australia) is an injectable anesthetic agent used for induction and maintenance of anesthesia in dogs and cats. Anecdotally it is useful in some zoological companion species as well. The author’s experience is with the use of alfaxalone as a preanesthetic or sedative for reptiles. The drug is available in Australia, and the United Kingdom, but not currently manufactured and distributed in the United States. It can be acquired legally using the Importation of Drugs regulations administered by the U.S. Food and Drug Administration (www.fda.vob/ForIndustry/ImportProgram/ucm173751.htm) (VIN editor: Link was not accessible as of 12-16-20).

Table 1. Suggested drug dosages for sedation in zoological companion animals. Dosages are based on clinical trial and error only. Note administration is by IM injection, which is considerably less stressful than restraint for IV injection.

Sedation in Birds

In the author’s experience, response to administration of midazolam and butorphanol for sedation is variable, and ranges from profound to barely perceptible. Onset after intramuscular injection is rapid, within 2–3 min. The profoundly sedated bird does not stand, but rests on the sternum with the head over the back or down. Some rest in a head down and tail up position. Respirations are generally slow and regular. In birds with respiratory distress, respiratory rate and effort is usually improved. In all cases, birds can be roused to a standing position, and react immediately to handling or discomfort. When left undisturbed, the bird returns to a sleeping position. Length of sedation is variable, but ranges from 20 min to several hours, with progressively decreasing level of sedation over time.

The largest factor affecting degree of sedation appears to be overall patient condition and demeanor, with more profound effects seen in ill or calm birds. For this reason, dose modification is based primarily on degree of debilitation. No species, sex or age predilections have been confirmed, but may emerge with expanded usage.

Psittacines

While every effort should be made to practice safe, atraumatic handling techniques, and even more importantly to train young birds to tolerate and accept the medical examination, in some cases, handling and examination produces extreme stress, continuous vocalizations, marked increased respiratory and cardiac rate, and hyperventilation. The author and others have observed cases of anxiety followed by seizures in parrots, in particular African grey parrots. In many of these cases, diagnostic tests and procedures did not indicate an underlying medical etiology for seizure, therefore these are assumed to be stress-induced. Sedation of these patients is extremely useful. The level of sedation varies from bird to bird, with some resting while undisturbed on the sternum, and most dozing while standing. Level of sedation decreases over time, and birds are generally standing and reacting to visual stimulation within 15–30 min. Recovery is improved with administration of flumazenil.

Sedation in Mammals

Combinations of midazolam and an opioid have variable results in zoological companion mammals, from profound to non-perceptible. In the author’s experience, the largest factor influencing effect appears to be clinical condition of the patient, rather than drug selection and/or species. If the initial combination does not provide adequate sedation, the dose may be slightly increased, or additional agents may be added, in particular ketamine and dexmedetomidine in low doses. Use of sedation has been associated with extremely low morbidity and mortality in clinical practice.

Sedation in Reptiles

The author and others have experience with the use of Alfaxan in reptiles in clinical practice. The best uses for Alfaxan in reptiles appear to be the following: a) induction (with or without preanesthetics) followed by immediate intubation and maintenance with isoflurane; and b) sedation (with or without other agents) combined with local analgesia for brief, minor procedures. Even when combined with premedications, Alfaxan alone does not appear to achieve an acceptable surgical plane of anesthesia at currently explored dosages, and is therefore best described as a preanesthetic/sedative agent for this species. Duration of action is variable but in general brief, often no more than 15 min. Full recovery is usually within 1 hour, but can be longer when combined with other agents, especially in debilitated patients. Dosages required appear to be higher in chelonians and green iguanas, and lower in snakes and leopard geckos. The author always begins with the lower end of the dosage range, adding boluses as needed to effect.

Indications for Sedation in Zoological Companion Animal Patients

Handling and Restraint

A number of patients experience stress during handling, and may present danger to the handler. For these patients, efficient, safe restraint (or use of a squeeze cage when applicable) plus administration of sedative agents can be extremely useful.

Respiratory Distress

A number of disease conditions produce variable degrees of respiratory distress in zoological companion animal patients. In some cases, distress is extreme, and handling is risky. Patients in respiratory distress are placed in a gently warmed incubator with oxygen for 10–15 min, then given midazolam by IM injection and returned quickly to the incubator. If additional sedation is desired, administer butorphanol by IM injection. The author has not noted a single case of worsening respiratory distress in sedated birds or mammals with sedation.

Diagnostic Sampling and Imaging

While sedation decreases anxiety and struggling during radiography, complete reduction of patient movement is superior with general anesthesia. However, calm handling and patience results in production of high-quality radiographs in patients for which general anesthesia is considered excessively risky. Collection of diagnostic samples, in particular blood is easier in the calm, sedated patient.

Establishment of Vascular Access

Many patients requiring vascular access are by necessity higher risk patients. Vascular access can be accomplished with the use of sedation, plus local analgesia over the catheterization site. Topical lidocaine gel is followed by injection of lidocaine at the site. Careful movement of the skin away from the vessel of choice is necessary to avoid inadvertent intravenous injection. For intraosseous catheterization, lidocaine is injected subcutaneously over the desired location, and into the periosteum of the bone.

Literature Cited

1.  ASA American Society of Anesthesiologists: Continuum of depth of sedation; definition of general anesthesia and levels of sedation/analgesia. ASA 2005-10-27 http://sedation.sgna.org/sedation_administration/sedation-levels (VIN editor: This link could not be accessed as of 12-16-20.)

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3.  Ishitobi S., T. Ayuse, H. Yoshida, K. Oii, K. Toda, and T. Miyamoto. 2009. Effects of midazolam on acquisition and extinction of conditioned taste aversion memory in rats. Neurosci. Lett. 450:270–274.

4.  Kain Z.N., M.B. Hofstadter, L.C., Mayes, D.M. Krivutza, G. Alexander, S.M. Wang, and J.S. Reznick. Midazolam: effects on amnesia and anxiety in children. Anesthesiology. 2000;93(3):676–684.

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6.  Nagore L., C. Soler, L. Gil, L. Serra, G. Soler and J.I. Redondo. 2012. Sedative effects of dexmedetomidine, dexmedetomidine-pethidine and dexmedetomidine-butorphanol in cats. J Vet Pharm Therap, doi: 10.1111/j.1365-2885.2012.01405.x.