Juergen Schumacher and Christoph Mans

Preanesthetic Evaluation

A thorough and complete evaluation of the patient should be conducted so that an effective anesthetic and analgesic protocol can be designed. A complete history and critical review of husbandry practices including diet, temperature, and humidity should be obtained because they will provide valuable information on the health status of the patient. The medical record of the patient should be reviewed, followed by a complete visual and physical examination. Particular attention should be paid to evidence of systemic disease, as well as signs of cardiovascular or respiratory compromise, which would affect the patient’s performance under anesthesia.

Diseases of the respiratory tract are commonly seen in reptiles and may affect both the upper and lower respiratory tract.⁹ Most commonly, a viral or bacterial cause is identified, and the patient may require effective antimicrobial therapy before induction of general anesthesia. Determination of respiratory rate and effort will provide limited information on the presence of respiratory tract disease. Imaging modalities such as radiography or computed tomography and collection of diagnostic samples will assist in identifying the severity and etiology of respiratory tract disease.

Assessment of cardiovascular performance should be part of the physical examination. Unfortunately, few studies have determined normal values for cardiovascular performance (e.g., heart rate and arterial blood pressures) in reptiles. Although reference values for various cardiac variables need to be established in common reptile species, determination of heart rate and rhythm, radiographic evaluation of cardiac morphologic characteristics, and echocardiography will give valuable information on cardiac performance and abnormalities. Reviews of reptile cardiology, including anatomy, physiology, and diagnostic procedures, have been published previously.10,11

Diagnostic samples such as fecal screens and hematologic and plasma biochemistry panels should be evaluated to determine the health status of the reptile. Reference values for common reptile species have been published and may provide important information on organ function and the presence of infectious and noninfectious disease processes. Imaging modalities such as radiography, ultrasonography, computed tomography and magnetic resonance imaging are performed as indicated by medical history and physical examination findings.

Supportive Measures

Many reptiles require supportive care before anesthesia because of underlying chronic disease processes and dehydration, which can often be identified during the preanesthetic evaluation. Effective fluid therapy is indicated for correcting fluid and electrolyte imbalances and returning the patient to a normovolemic state. Intravenous (IV) or intraosseous (IO) fluid therapy is most effective and should be administered as a constant rate infusion if vascular or intraosseous access has been established (Figure 12-1). IV catheters can be placed percutaneously in the jugular veins of chelonians (Figure 12-1, A) and in ventral tail veins of lizards. After cut-down techniques, IV catheters can also be placed in the cephalic and ventral abdominal veins of lizards (Figure 12-1, B) or in the jugular veins of snakes. In lizards, the tibia is a common site for IO catheterization (Figure 12-1, C) when IV access is not possible.

In cases of suspected or confirmed bacterial and fungal infections, effective antimicrobial/antifungal therapy should be initiated before the anesthetic event but preferably after the collection of material for culture and sensitivity testing. Particular attention should be paid to signs of respiratory or cardiovascular compromise because these will affect the anesthetic plan, including selection of drugs, dosages, and monitoring equipment, and the requirement for supportive care measures during anesthesia, such as intermittent positive pressure ventilation (IPPV).

Analgesia

Until recently, relatively little work had been done to determine effective drugs and dosages in commonly kept reptile species. Reptiles are a diverse group of animals with often pronounced taxonomic differences in response to analgesic agents and dosages. Therefore application of drugs and dosages derived from one species to another should be done with caution. It is well-known that application of preemptive analgesia in mammals is more effective in the management of pain and should likewise be provided to reptiles undergoing potentially painful procedures.

A balanced analgesic regimen takes advantage of distinct analgesic pathways and may include the systemic administration of different classes of analgesics (e.g., nonsteroidal antiinflammatory drugs [NSAIDs] and opioids) and/or the provision of local anesthetics. At present, local anesthetic regimens are not commonly utilized in reptiles. Although little data are available on effective drugs, dosages, and techniques, local anesthesia in combination with systemic analgesic therapy offers the advantages of reduced dosages for systemic analgesic agents and will reduce maintenance requirements during general anesthesia. The same principles established in domestic animals should be followed and should include administration of lidocaine or preferably the longer acting bupivacaine at the surgery site. Advanced techniques such as spinal anesthesia have been investigated and are described further on. It should be part of the anesthetic protocol to provide preoperative, intraoperative, and postoperative analgesia. Opioid agents are most effective in controlling acute pain resulting from trauma and surgery, whereas NSAIDs are most commonly used for the management of chronic pain.1,^12–14

Common opioid analgesic agents used in reptiles to manage acute pain include morphine (1 to 2 mg/kg) and hydromorphone (0.5 to 1 mg/kg).1,13 At present, the most common NSAID used in reptiles is meloxicam at 0.2 mg/kg IV, intramuscularly (IM), or per os (PO) every 24 to 48 hours. For further information on effective pain management and protocols see Chapter 18.

Sedation

Sedation is commonly used in human and domestic animal veterinary medicine to facilitate diagnostic sample collection, medical treatment, and positioning for diagnostic imaging (Figure 12-2, A-C). Sedation is defined as a state of drug-induced altered consciousness that allows the patient to better tolerate stressful or unpleasant procedures without depressing protective airway reflexes or having a significant cardiopulmonary depressant effect.¹⁵ Currently, diagnostic procedures are often performed in conscious reptiles or under general anesthesia. For sedation of reptiles, a variety of injectable anesthetic drugs at lower subanesthetic doses can be used alone or, preferably, in combination.^16–19 Drugs used for sedation should be short-acting or reversible, so that prolonged or unpredictable recoveries are avoided. Sedative drugs should be chosen based on the desired level of sedation (mild to deep), the general condition of the patient, and the diagnostic and/or therapeutic procedure to be performed. Commonly used sedative protocols are summarized in Table 12-1. Under sedation, spontaneous respiration should be maintained and reptiles should respond to painful stimulation (e.g., toe pinch). The combination of procedural sedation, with either local or spinal anesthesia, offers the possibility of performing surgical or invasive procedures that would otherwise only be possible under general anesthesia (Figure 12-2, D). When sedation is combined with local or spinal anesthesia, the dose of general anesthetic drugs can be reduced, which will lead to reduced cardiovascular depression, more rapid recoveries, and potentially fewer anesthetic complications compared with general anesthesia.

Regional Anesthesia and Analgesia

Anesthetic Agents

Before administration of any anesthetic or sedative drugs, reptiles should be maintained within their preferred optimal temperature zone (POTZ), and the core body temperature should be monitored throughout the chemical restraint period. A variety of agents representing different classes of drugs are often used either alone or in combination, depending on the desired level of sedation or anesthesia. Preference should be given to agents that have a specific antagonist available so that recovery time is reduced and the patient is returned as quickly as possible to the preanesthetic state. Similar drugs and drug combinations can also be chosen for premedication before induction of general anesthesia. If the patient is scheduled for a painful procedure, it is recommended that an analgesic agent such as an opioid be included in the preanesthetic protocol.

Most injectable protocols in reptiles include the administration of the dissociative anesthetic agent ketamine in combination with synergistic agents such as midazolam, opioid agents, and alpha-2 agonists (e.g., dexmedetomidine). The addition of synergistic agents such as an alpha-2 agonist will reduce the amount of ketamine required to induce sedation and immobilization. Therefore recovery times after administration of a specific alpha-2 antagonist (e.g., atipamezole) or benzodiazepine antagonists (e.g., flumazenil) will be greatly reduced. Although injectable agents alone can be used to facilitate short, minor procedures, induction and maintenance of a surgical plane of anesthesia for prolonged, invasive procedures is often based on administration of an inhalational agent such as isoflurane or sevoflurane.

Ketamine, a dissociative agent with dose-dependent anesthetic, sedative, and analgesic properties, is frequently used in reptile anesthesia. However, when administered alone, muscle relaxation is considered inadequate and recoveries excessively prolonged, especially when high dosages are used. Administering an alpha-2-adrenergic agonist (e.g., dexmedetomidine) or a benzodiazepine (e.g., midazolam) along with ketamine allows for reduction of the dose of ketamine administered and provides the benefit of partial reversibility of these protocols, leading to more rapid recoveries and increased safety. Even at lower subanesthetic dosages (less than 5 mg/kg), ketamine can provide additional sedation and analgesia if combined with other anesthetic drugs.24,33

Tiletamine/zolazepam (Telazol, Fort Dodge Laboratories, Fort Dodge, Iowa) is a commercially available drug combination composed of a dissociative anesthetic (tiletamine) and a benzodiazepine (zolazepam). Dosages of 2 to 10 mg/kg have been recommended for sedation, induction of general anesthesia, or facilitation of intubation.5,6,20 The anesthetic efficacy of tiletamine/zolazepam can be unpredictable, and recovery may be prolonged. In dehydrated patients or in those with underlying renal or metabolic disorders, the use of this drug combination is contraindicated.²⁰ Tiletamine/zolazepam is also useful in large or dangerous species (e.g., crocodilians and large monitor lizards), and although not recommended for routine use in most reptiles, some have reported consistently good results (Mader DR: Pers. com., Feb, 2013 ).

Alpha-2-adrenergic agonists, such as medetomidine and dexmedetomidine, provide sedation, muscle relaxation, and possibly, analgesia in reptiles. Dose-dependent cardiovascular depression has been documented in reptiles after medetomidine administration.19,34,35 Alpha-2-adrenergic agonists are commonly used in combination with ketamine, especially in chelonian species, for safe, reliable, and reversible sedation but can also be combined with benzodiazepines for procedural sedation.^36–41 Combining ketamine with medetomidine or dexmedetomidine allows reduction of both drug dosages, and reversibility of the alpha-2-adrenergic agonists with atipamezole will lead to faster and more predictable recoveries. Morphine or hydromorphone can be added to alpha-2 adrenergic-agonist-plus-ketamine protocols in cases in which analgesia is needed.³⁷ If morphine or hydromorphone are used, reversal with naloxone (0.04 to 0.2 mg/kg, subcutaneously [SC]) should be considered after termination of the anesthetic procedure, particularly in freshwater turtles, if respiratory depression is profound or if prolonged recoveries or renarcotization are to be avoided.³⁷

Benzodiazepines, such as midazolam and diazepam, have sedative and muscle relaxant properties. Midazolam is water soluble, can be administered SC, IM, and IV, and is considered a more appropriate choice than diazepam, which is not recommended for IM or SC injection.⁴ Midazolam, used alone, provides mild but highly variable sedation, which may be sufficient for minor clinical procedures.^16,17 Midazolam, combined with ketamine or an alpha-2-adrenergic agonist, reduces all drug dosages and attenuates the dose-dependent cardiovascular depressant effects and prolonged recoveries commonly observed with high dosages of ketamine. The effects of benzodiazepines can be antagonized with the use of flumazenil (0.05 mg/kg, SC), which shortens recovery from sedation or anesthesia.⁴¹

Propofol, a short-acting nonbarbiturate anesthetic agent, can be administered IV or IO to provide short-term anesthesia, facilitating procedures such as placement of an esophagostomy tube or abscess debridement, or to induce general anesthesia and allow for endotracheal intubation and maintenance of anesthesia with an inhalational anesthetic agent. Respiratory depression is more profound when propofol is administered rapidly.20,42 Because propofol does not accumulate in tissues and is rapidly metabolized, complete recovery can be expected with assisted ventilation in cases of overdose. Propofol requires intravascular administration, which can be challenging in some species. Recently, published articles have described complications secondary to accidental extravascular injection of propofol intrathecally and into the subcarapacial sinus or the coccygeal vein of chelonian species.^43–45 Complications associated with intrathecal propofol injection included forelimb and hindlimb paralysis, coma, and spinal necrosis.^43–45 In addition, complications with propofol in sea turtles have been reported and include respiratory arrest and death several hours postanesthesia (Mader DR: Pers. com., Feb 2013).

Alfaxalone is a short-acting steroid anesthetic due for commercial release in the United States in 2013 that has a long history of use in other countries for induction of sedation or anesthesia. Alfaxalone is rapidly cleared and its metabolism is independent of organ function. Similar to propofol administration, alfaxalone administration is associated with smooth and rapid recoveries and dose-dependent cardiovascular and respiratory depression in mammals.46–48 One major advantage of alfaxalone is that it can be administered IM as well as IV.^46,49–52 However, dose volumes are often large and may need to be divided between injection sites; thus the cost may be prohibitive in larger patients.

The IV administration of alfaxalone in Green Iguanas (Iguana iguana) (10 mg/kg) resulted in rapid induction of light anesthesia, which allowed endotracheal intubation.52,53 The effects of IM administration of alfaxalone have been investigated in Red-eared Sliders, Horsfield’s tortoises (Agrionemys horsfieldii) and Green Iguanas.^49–51, At a dose of 10 mg/kg IM light-to-moderate sedation, suitable for minor nonpainful procedures such as blood collection and physical examination was induced. At 20 mg/kg, light anesthesia was induced and allowed for endotracheal intubation in all Red-eared Sliders and Green Iguanas, but only in about half of the Horsfield’s tortoises, which were moderately to deeply sedated. The administration of 30 mg/kg in Green Iguanas resulted in surgical anesthesia for up to 40 minutes.⁵⁰ The induction times after IM alfaxalone administration in Green Iguanas were short (approximately 5 to 10 minutes at 24°C to 27°C), and recovery was smooth. The induction, duration, and recovery times after alfaxalone administration were significantly shorter at 35°C compared with 20°C in Red-eared Slider Turtles.⁴⁹ At 20 mg/kg IM, the induction times were 19 ± 6 (20°C) and 7 ± 5 minutes (35°C), and the plateau phase lasted 28 ± 13 (20°C) or 8 ± 5 (35°C) minutes.⁴⁹

Inhalational agents such as isoflurane and sevoflurane can be used for both induction and maintenance of anesthesia in many reptiles (but often not chelonians and crocodilians due to breath holding). Both agents offer the advantages of relatively fast induction and recovery times as well as limited organ toxicity, especially in patients with renal or hepatic impairment. Sevoflurane is commonly used in human and domestic animal anesthesia and has a low blood solubility. A rapid increase in alveolar concentration can be seen during induction with this agent. The low blood solubility allows for rapid changes in anesthetic depth. Investigations of the use of sevoflurane in various reptile species have shown variable results in that some species have not achieved a surgical plane of anesthesia. Few studies have investigated comparative cardiopulmonary effects of sevoflurane versus isoflurane in reptiles.¹⁴ Administration of inhalational agents follows similar principles as those established for domestic animal anesthesia. After induction of anesthesia, the trachea should be intubated with an appropriately sized endotracheal tube, which should be connected to a non–rebreathing (body weight, less than 10 kg) or rebreathing system. IPPV should be performed in all reptiles. The concentration of the inhalational agent necessary to maintain a surgical plane of anesthesia depends on the health status of the patient. Minimum anesthetic concentrations (MAC) of isoflurane and sevoflurane have been determined in Green Iguanas and are 1.8% to 2.1% and 2.1% to 4.1%, respectively.^54,55 Maintenance requirements for a surgical plane of anesthesia have been reported to be 2% to 3% for isoflurane and 3.5% to 4.5% for sevoflurane.⁵ Like all anesthetic agents, both isoflurane and sevoflurane will cause cardiopulmonary depression as shown in Green Iguanas, in which isoflurane at 3% induced severe hypotension.⁵⁶ Therefore the concentrations of both agents would have to be reduced in debilitated patients. A study in Green Iguanas has shown that cardiopulmonary effects of both inhalational agents are similar; however, sevoflurane will produce faster induction and recovery times.¹