Abstract

The clinical use of anesthetic and analgesic agents in reptiles presents a number of unique challenges due to the diversity of the Class Reptilia with respect to natural history, size, anatomy, and physiology. Reptiles are commonly maintained as companion animals, are widely displayed in zoological institutions, and many species serve as subjects in laboratory facilities. Therefore, developing an understanding of anesthetic and analgesic efficacy across reptile species is important. Current obstacles to our understanding of both reptile anesthesia and analgesia include: 1) inadequate knowledge of anesthetic and analgesic efficacy, safety, dosages and dosing frequency across species; 2) inability to monitor anesthetic depth; 3) pharmacokinetics of anesthetic and analgesic drugs; 4) the unknown relationship between risks and benefits for specific drugs; and 5) subjectivity and difficulty associated with pain assessment. The objective of this presentation is to provide a current perspective on the practical application of anesthetics and analgesics in commonly maintained pet reptile species.

Clinical Reptile Anesthesia

The diversity of reptiles in terms of natural history, size, anatomy, and physiology presents a unique clinical challenge to the veterinarian. However, as with all nondomestic species, the application of safe and effective anesthetic techniques is essential for those veterinarians dealing with reptile patients, and effective anesthetic application will facilitate performing complete physical examinations, collecting appropriate and high-quality diagnostic samples, and realizing successful surgical procedures.

Reptiles differ from mammals physiologically and anatomically, and therefore, it is difficult to directly extrapolate from methods used in mammalian anesthesia. Reptiles are poikilothermic; their body temperature is directly dependent on environmental temperature, and therefore, the temperature at which one maintains a patient is an important factor during anesthesia, due to the fact that the metabolism and excretion of drugs in reptiles is directly related to environmental temperature.^2,4,7,8,10 The reptile patient should be maintained at its preferred optimal body temperature (POBT) in order to better predict the physiologic effects of anesthetic drugs, as well as drug metabolism and excretion. Preferred optimal body temperature is generally considered to be 20–25°C in temperate and aquatic species, and 25–35°C in tropical species.^2,4,7,8,10

Procedural sedation is defined as the state of drug-induced altered consciousness, which allows the patient to better tolerate stressful or unpleasant procedures, without depressing protective airway reflexes or having a significant cardiopulmonary depressant effect. Procedural sedation is commonly used in human and domestic animal veterinary medicine to facilitate diagnostic sample collection, as well as diagnostic imaging. A variety of injectable drugs are reported to be effective when administered alone, or in combination, for sedation of reptiles. The preferred route of sedative drug administration is subcutaneous (SC) in the cranial half of the body, the advantages of which include access to a variety of subcutaneous sites requiring minimal manual restraint or patient manipulation, and the capability of administering larger volumes in a single location.^7,10 Preference should be given to sedative combinations, which are partially or completely reversible, in order to avoid prolonged or unpredictable recoveries.^3,4,7,10,14 Commonly used sedative protocols were recently published.¹⁰

For general anesthesia, a variety of injectable anesthetic protocols have been reported in different reptile species, but published dosages vary widely for many drugs, which is partially due to the fact that different species of reptiles require different dosages to achieve the same effect. In general, we recommend avoiding the administration of high doses of a single anesthetic agent, and instead, consider protocols in which multiple drugs are combined with synergistic actions, thereby requiring lower dosages for each drug. Additionally, using readily reversible drug protocols will provide for more rapid recoveries. Since most deleterious side effects (e.g., prolonged recovery, cardiopulmonary depression) associated with anesthetic and sedative drug administration are dose-dependent, individual drug dosage reduction and reversibility will result in fewer complications and improved recoveries. Commonly used parenteral anesthetic protocols were recently published.¹⁰ All reptiles undergoing general anesthesia for longer than 15 minutes should be intubated in order to provide assisted ventilation and/or to deliver inhalant anesthetic gases for maintenance of general anesthesia. Isoflurane and sevoflurane are the most commonly used maintenance inhalant anesthetics in reptiles, but most reptiles develop apnea or marked bradypnea and hypoventilation, when anesthetized.^7,10 Therefore, constant ventilatory support (intermittent positive pressure ventilation or IPPV; approximately 4 breaths per minute) should be provided throughout the anesthetic procedure.^7,10 The guideline of limiting peak inspiratory pressure to < 10 cm H₂O is recommended to limit lung or air sac damage.¹⁰

Local anesthesia is currently underutilized in reptile medicine, but offers significant benefits, such as the ability to reduce the depth of general anesthesia or sedation for certain surgical procedures. In some cases, local anesthesia can be used solely in manually restrained animals for minor surgical procedures.^7,10 Common indications for the use of local anesthetics as part of an anesthetic protocol in reptiles include distal limb surgery, tracheal or lung washes, or infiltration of incision sites prior to coeliotomy. Lidocaine and bupivacaine are readily available in most veterinary clinics, and both are effective local anesthetics in reptiles.

Monitoring of anesthetic depth and cardiopulmonary function is a continual clinical challenge in reptiles. Approaches to anesthetic monitoring include righting reflex; corneal reflex in those species with eyelids; heart rate via auscultation, application of an ultrasonic Doppler device or sonography; heart rate and rhythm using an electrocardiograph; pulse oximeter indirectly estimates arterial oxygen-hemoglobin saturation by applying a reflectance probe (e.g., mammalian rectal probe); respiratory rate; and body temperature.^7,10

Recovery from anesthesia can be best accomplished by placing the reptile in a temperature-controlled environment, antagonizing any benzodiazepines and alpha-2-adrenergic agonists, periodically assessing muscle tone, reflexes, and spontaneous breathing. Until spontaneous breathing is observed, an Ambu bag should be attached to the endotracheal tube and IPPV performed, since room air for ventilation is preferred during recovery because high oxygen concentrations in the lungs have been shown to significantly delay the return of spontaneous respiration.^7,10 Fluid therapy and pain management should be continued during the recovery phase.

Clinical Reptile Analgesia

The important questions are whether reptiles experience "pain," and can we recognize pain in reptiles? Is the perception of pain by a reptile equivalent to that of a mammal? We will never be able to objectively answer whether reptiles feel pain because they simply cannot tell us. However, like human infants or mammals, should the inability to verbally communicate dictate whether pain is being perceived or an analgesic drug administered? I would argue no! Because the word "pain" conjures up anthropocentrism for some scientists and clinicians, nociception and antinociception are used when referring to pain and analgesia. This stems from the controversy concerning whether or not non-mammalian species have central and peripheral nervous system structures and pathways, which are capable of "receiving and processing" noxious stimuli and responding appropriately. In other words, can non-mammals "experience" pain, or are they merely capable of demonstrating a "reflexive" response to a noxious stimulus (nociception)? Like mammals, reptiles possess all of the anatomical structures considered critical for the recognition of pain: peripheral nociceptors, appropriate central nervous system structures and pathways, opioid receptors and endogenous opioids, reduction of nociceptive response with analgesics (although data are sparse), pain avoidance learning, and suspension of normal behavior with pain.^4,9,11 Thus, the physiological and anatomical requirements for pain and analgesia appear to be remarkably similar among all vertebrate species. Therefore, as clinicians, it is our contention that because of our limited understanding of pain and analgesia in reptiles, we should err on the side of reptile patient wellbeing and make the assumption that conditions considered painful in humans and other mammals should be assumed to be painful across all other vertebrate species.

Measuring pain in reptiles is the most difficult hurdle in the study of analgesic efficacy. In mammals, it is well established that perioperative pain management facilitates recovery and healing, reduces morbidity and mortality, and contributes to more rapid return to normal behavior.^9,11 An objective understanding of normal behavior of a particular species and the ability to differentiate the presence of abnormal behavior indicative of discomfort are critical to the study of pain and analgesia. Therefore, one must first have an understanding of normal species-specific behavior within the environmental context in which that behavior is being displayed, in order to be able to discriminate behavior associated with pain. Methods for assessing and measuring pain in reptiles have been described previously.^9,11-13

Opioids, the most effective drugs for controlling pain in mammals, are classified according to receptor subtypes - µ (mu), κ (kappa), and δ (delta). For pain management in mammals, many clinicians prefer administering a µ-opioid receptor agonist (e.g., hydromorphone, buprenorphine) or a mixed-opioid, κ-receptor agonist-µ-receptor antagonist (e.g., butorphanol). Butorphanol tartrate (a kappa-opioid receptor agonist), administered at mammalian-derived dosages, was once believed to be the most effective analgesic drug for use in reptiles.⁶ However, more recent data demonstrate that mu-opioid receptor agonists, such as morphine, hydromorphone, or tramadol, provide the most effective analgesia in all reptile species other than snakes, while butorphanol appears to be no more effective than saline.^1,9,11-13 Commonly used anesthetic protocols were recently published.^9,11 Extrapolation of analgesic efficacy across orders and species remains a major limitation, and there is a clear need for evaluating analgesic drugs across a variety of clinical situations, particularly as they apply to post-surgical pain. Objectively derived methods for evaluation of pain in animals are critical, but these methods must be species- and context-specific. In addition, determining pharmacokinetic parameters, duration of drug efficacy, species-specific requirements, and deleterious side effects of opioid drugs in different reptile species remains critical to continue to advance the field of reptile analgesia.

References

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