ANESTHESIA AND ANALGESIA

Safe and effective anesthesia and analgesia can be challenging in reptiles because of their unique anatomy and physiology and their variable response to anesthetic and analgesic drugs and dosages. Commonly used anesthetic and analgesic agents may also unpredictably compromise homeostasis of the reptilian patient. For successful anesthesia of the variety of reptilian species commonly seen by the practitioner, a thorough knowledge and understanding of their unique anatomy, physiology, and the pathophysiology of diseases is essential. Species and individual differences may be present, and a good understanding of reptile disease processes is recommended for selection and administration of an effective and safe anesthetic protocol for the patient. Reptiles are poikilothermic animals, and all body functions are dependent on the environmental temperature. Reptiles have a species specific preferred optimal temperature range (POTR) in which all organ systems work most effectively. Consequently, the patient's response to drugs including anesthetic and analgesic agents also depends on the environmental temperature.

Anesthesia and analgesia are important specialties in reptile medicine that need further studies to determine effective drugs and dosage regimen. Few studies have determined the cardiopulmonary effects of anesthetic agents and the pharmacokinetics and effectiveness of analgesic agents in reptiles. Along with the advances of diagnostic and surgical procedures in reptile medicine, safe and effective anesthetic techniques including appropriate analgesic therapy are required. This chapter describes clinical anesthetic and analgesic techniques in reptiles, and comprehensive reviews on reptile anesthesia have been published previously.

ANATOMY AND PHYSIOLOGY

The anatomy and physiology of reptiles differs considerably from mammalian and avian species, and knowledge of normal anatomic structures and normal reptilian physiology is essential to successfully anesthetize and monitor the reptilian patient. All anesthetic agents commonly used in reptile anesthesia have profound effects on cardiopulmonary performance, and a detailed understanding of normal respiratory anatomy and function is essential to select a safe and effective anesthetic regimen and facilitate appropriate monitoring of cardiopulmonary function in the preoperative, intraoperative, and postoperative periods.

Respiratory Anatomy and Physiology

The structure and function of the reptilian respiratory system not only differs considerably from mammalian and avian species, but differences are also apparent between orders of reptiles and between species. All reptiles lack a functional diaphragm, and the force to move air during inspiration and expiration comes from movement of the intercostal, pectoral and abdominal musculature, resulting in changes of intrapulmonary pressure.

The glottis of snakes is located rostrally, and air enters through the external nares, the nasal sinuses, and the internal nares. The trachea consists of incomplete cartilagenous rings and bifurcates into short bronchi at the level of the heart. The lungs are elongated sac-like structures lined with respiratory epithelium. Although the left lung is vestigal in most snake species, the right lung extends into a caudal air sac, lined with nonrespiratory epithelium. The glottis of carnivorous lizards is located more rostrally when compared with herbivorous species, where it is commonly found at the base of the tongue (Figure 27-1). Lizards have incomplete tracheal rings, and the trachea bifurcates approximately at the base of the heart. The lungs of most lizard species are single-chambered organs that extend caudally into an air sac. Iguanids have multichambered lungs that consist of an anterior and posterior chamber. In chelonians, the glottis is located at the base of a fleshy tongue. The trachea has complete tracheal rings, is relatively short, and bifurcates into a left and right intrapulmonary bronchus at the level of the thoracic inlet. Turtles and tortoises have paired, multichambered, relatively rigid lungs. In crocodilians, the glottis is located behind the epiglottal flap. The lungs of crocodilians are complex and multichambered, and the bronchi branch into multiple internal lobes.

Reptile respiratory physiology differs considerably between orders and species, especially terrestrial and aquatic species. The lungs are the major organ for gas exchange (oxygen and carbon dioxide); however, some aquatic snake and turtle species feature cutaneous gas exchange, primarily for the elimination of CO2. Many reptiles, especially aquatic species, are also capable of converting to anaerobic metabolism during long periods of apnea. Reptilian lungs have high compliance values and are relatively easy to inflate. Reptiles increase the minute volume by increasing the respiratory rate. In comparison with mammals, reptiles have larger lung volumes; however, the surface area for gas exchange is approximately 20% of that of a mammal of comparative body mass.

Reptilian respiration is controlled by hypoxia and hypercapnia and environmental temperature. Specific receptors increase ventilation during periods of low O₂ and high CO₂. In most reptile species, hypercapnia causes increases in tidal volume and periods of hypoxia increase respiratory rate. In reptiles, the stimulus to breathe comes from low oxygen concentrations. Respiratory rate has been shown in tortoises to increase during hypercapnia but decrease during hypoxia. The higher demand for oxygen during increased temperature or after prolonged dives in aquatic species is met by increasing the tidal volume and not the respiratory rate. In an oxygenenriched environment, reptiles decrease ventilation, characterized by a decrease in respiratory rate and tidal volume. Intrapulmonary shunts, which represent the portion of pulmonary blood bypassing gas exchange, reduce the efficiency of gas exchange in the lungs and result in a reduction of arterial PO₂ concentrations.

PREANESTHETIC EVALUATION

Reptiles are often seen with chronic disease processes characterized by poor body condition, dehydration, and the presence of secondary bacterial and fungal infections. In many cases, disease is a result of inadequate environmental conditions, and a careful review of husbandry practices and onset of clinical signs of disease is mandatory. For reduction of anesthetic risk and stabilization of the patient's condition, supportive care measures such as fluid therapy and nutritional support should be initiated before anesthesia. In patients with identified infectious bacterial disease processes, treatment should include effective antimicrobial agents, as determined with culture and sensitivity testing. Particular attention should be paid to the cardiopulmonary status and performance of the patient. Rate and depth of respiration should be carefully evaluated for signs of respiratory disease requiring treatment before anesthesia. Baseline respiratory and heart rates and an accurate body weight should be recorded as part of the physical examination.

For assessment of the health status of the reptile, collection of a venous blood sample for hematologic and plasma biochemical parameters is indicated. Minimally, the packed cell volume (PCV), total protein, and glucose levels should be determined. In some patients, however, such as crocodilians, large lizards, and chelonians, sedation or general anesthesia may be necessary to obtain a blood sample and other diagnostic specimen. Additional diagnostic tests should be performed as indicated and should include fecal screens for parasites, collection of biopsy specimen, and aspirates for cytologic and microbiologic evaluation. Imaging procedures such as radiography and ultrasound can be performed in most species with manual restraint alone and are valuable tools in determination of the health status of the patient and identification of organ abnormalities.

Before anesthesia, the patient should be acclimated to temperature and humidity levels appropriate for the species. Fluid therapy should be initiated with indication of volume depletion, on the basis of physical and laboratory findings. The goal of fluid therapy is to restore homeostasis and maintain organ function, and administration of a balanced electrolyte solution is indicated in most patients. Fluid requirements and selection and treatment of disturbances of hydration status have been reported for reptiles. A constantrate infusion of fluids is preferable over intermittent boluses; therefore, every effort should be made to place an intravenous (IV), or alternatively an intraosseous (IO), catheter. In reptiles with electrolyte imbalances, the underlying problem should be identified and corrected. Normal electrolyte levels in reptiles are species dependent, and a wide range of values has been reported for various species.

In patients in which physical and diagnostic findings indicate that the animal is in pain and discomfort, appropriate analgesic therapy should be initiated before anesthetic induction, as part of a preemptive analgesic regimen.

PREMEDICATION

The type and amount of preanesthetic agents depend on the species of reptile to be anesthetized and the procedure to be performed (Table 27-1). Large crocodilians, large and venomous snakes, and chelonians may need administration of an injectable agent to facilitate handling and induction of anesthesia with an inhalational (e.g., isoflurane) or injectable (e.g., propofol) agent.

Reptiles scheduled to undergo surgical or anticipated painful procedures should be administered a preoperative analgesic agent such as butorphanol or buprenorphine for a balanced anesthetic regimen. Administration of these agents provides intraoperative and postoperative analgesia and often reduces anesthetic maintenance requirements of the inhalational agent. However, a study in Green Iguanas (Iguana iguana) determined that butorphanol does not have significant isoflurane-sparing effects.The cardiac anesthetic index of isoflurane in Green Iguanas has been determined to be more than 4.32 and is not affected by the administration of butorphanol. Both butorphanol and buprenorphine, if used alone even at high doses, have minimal to moderate sedative effects in most reptile species. Green Iguanas premeditated with intramuscular (IM) butorphanol (2 mg/kg) showed no changes in heart and respiratory rates 30 minutes after drug administration when compared with baseline values.14as Administered before mask induction, butorphanol or buprenorphine results in decreased struggling of the patient, and most animals are less likely to hold their breath during induction of anesthesia.

Benzodiazepines such as diazepam and midazolam if used alone have minimal sedative effects in most reptile species. Midazolam has been reported as a sedative agent in Redeared Slider Turtles (Trachemys scripta elegans) at a dosage of 1.5 mg/kg intramuscularly and resulted in a sedative plane suitable for minor manipulations.16 In most anesthetic regimens, benzodiazepines are combined with dissociative agents such as ketamine and opioid agents (butorphanol, buprenorphine). Anticholinergic agents such as atropine and glycopyrrolate to reduce respiratory secretions are not routinely used in reptiles.

Hypothermia or deliberate cooling is not an acceptable means for the immobilization of reptiles. Although it causes immobilization, it does not provide analgesia and anesthesia. Hypothermia is painful and associated with decreased metabolism and may also result in necrosis of the brain. Safe and effective injectable and inhalational anesthetic agents are available for reptiles, and hypothermia is an unacceptable inhumane means for immobilization of reptiles.

INJECTABLE ANESTHETIC AGENTS

Many injectable agents have been used and investigated for induction and maintenance of anesthesia in reptiles (see Table 27-1). Most agents, especially when used alone at high dosages, are associated with pronounced cardiopulmonary depressant effects, prolonged induction and recovery times, and poor muscle relaxation and analgesia during maintenance of anesthesia. Species and individual differences are commonly seen in response to parenteral anesthetic agents.

Most commonly, the dissociative anesthetic agent ketamine HCl is used in reptiles to produce immobilization and induce anesthesia. Ketamine has a wide range of safety in most reptiles and can be administered intramuscularly and intravenously. Ketamine alone results in poor muscle relaxation, minimal analgesia, and, if used at high dosages, prolonged recovery times. In snakes, ketamine alone has been shown to produce respiratory depression, hypertension, and tachycardia.l' Therefore, it is rarely used alone and often combined at lower dosages with synergistic agents such as benzodiazepines (e.g., diazepam, midazolam), opioid agents (e.g., butorphanol, buprenorphine), or alpha₂-adrenergic agonists (e.g., medetomidine). The addition of synergistic agents allows for the dose of ketamine to be reduced and results in better quality of anesthesia, characterized by more rapid and smoother induction and recoveries and improved muscle relaxation and analgesia during maintenance. A study of ketamine (60 mg/kg IM) alone or in combination with xylazine (2 mg/kg 1M) or midazolam (2 mg/kg IM) in Red-eared Sliders (Trachemus scripta elegans) resulted in various degrees of sedation.

Telazol, a combination of tiletamine and zolazepam, has been used for immobilization and induction of anesthesia in reptiles; however, at higher doses (>6 mg/kg IM), it is associated with prolonged recovery times (>48 to 72 hours), especially in chelonians. At a dose of 2 to 4 mg/kg IM, tiletamine / zolazepam is useful to facilitate handling of large chelonians, lizards, and snakes.

The alpha₂-agonist medetomidine has been investigated as a sedative agent in reptiles, especially in potentially dangerous species and for short procedures. Similar to use in domestic animals, medetomidine should not be used alone and therefore is commonly combined with a low dose of ketamine and an opioid agent such as butorphanol. Administration of this combination facilitates handling of large reptile species and allows minor procedures to be performed, such as abscess debridement, shell repair, and collection of diagnostic samples. The specific alpha₂-antagonist atipamezole should be administered at five times the medetomidine dose to reverse the effects of the alpha₂-agonist at the end of the procedure.

Atipamezole administered intravenously to Gopher Tortoises (Gopherus polyphemus) immobilized with ketaminemedetomidine resulted in severe hypotension, and the conclusion was that this agent should not be given via the IV route in turtles and tortoises. The sedative effects of medetomidine (150 µg/kg IM) alone have been reported in Desert Tortoises (Gopherus agassizii). At the dosage used in this study, all tortoises were sedated; however, pronounced cardiopulmonary depression, including decreases in heart and respiratory rate and hypotension, was present IV administration of a ketamine (5 mg/kg)-medetomidine (0.1 mg/kg) combination in Gopher Tortoises resulted in effective short-term immobilization adequate for minor procedures. In this study, moderate hypoxemia and hypercapnia and moderate increases in arterial blood pressures were seen. Therefore, recommendation is to provide supplemental oxygen and assist ventilation with this combination.

Propofol an ultra-short-acting induction agent is the injectable agent of choice in reptiles if vascular access is available (Figure 27-2). Propofol has been used in a variety of reptile species for induction and maintenance of anesthesia. Propofol has to be administered intravenously or intraosseously and can be used for both induction and maintenance of anesthesia via constant rate infusion (0.3 to 0.5 mg/kg/ minute) or with intermittent boluses (0.5 to 1 mg/kg). Propofol does not contain preservatives, and sterile techniques should be used with administration of the agent.

Perivascular injections are not associated with tissue necrosis; however, the potential for infection is present. Although these injections have been shown by some investigators to be effective, the author does not use the intracardiac route for propofol administration for the previous reason. Similar to use of barbiturate induction agents, administration of propofol results in pronounced cardiopulmonary depressant effects in reptiles and therefore should be titrated to effect. Studies in humans and domestic animals have shown that propofol causes systemic hypotension, decreased myocardial contractility, and respiratory depression. Rapid bolus injection of propofol during induction is commonly associated with apnea. The advantage over other induction agents such as barbiturate agents is the shorter duration of action of propofol.

Agent	Lizards	Snakes	Chelonians	Comments
Alphaxalone/alphadolone (mg/kg)	6-15 IM, IV	6-15 IM, IV	6-15 IM, IV	Species differences
Diazepam (mg/kg)	0.2-2 IM, IV	0.2-2 IM, IV	0.2-1 IM, IV	All species
Isoflurane (%)	Induction: 4-5 Maintenance: 1.5-3	Induction: 5 Maintenance: 2-3	Induction: 4.5 Maintenance: 2-3	All species
Ketamine (mg/kg)	5-20 IM, IV	10-60 IM, IV	5-50 IM, IV	Rarely used alone
Medetomidine (mg/kg)	0.05-0.1 IM	0.1-0.15 IM	0.03-0.15 IM	Reversible with atipamezole
Midazolam (mg/kg)	1-2 IM, IV	1-2 IM, IV	1-2 IM, IV	All species
Propofol (mg/kg)	3-5 IV, IO	3-5 IV	2-5 IV, IO	Induction agent of choice
Sevoflurane (%)	Induction: 7-8 Maintenance: 2.5-4.5	Induction: 7-8 Maintenance: 2.5-4.5	Induction: 7-8 Maintenance: 2.5-4.5	Species differences
Tiletamine/zolazepam (mg/kg)	2-6 IM, IV	2-6 IM	2-4 IM	Prolonged recoveries, especially in chelonians

Routes of Drug Administration

In most reptiles, IM administration of anesthetic agents is most effective and practical. Although oral administration of sedative agents has been investigated in domestic and nondomestic species, in reptiles, this route of drug administration is not reliable. Subcutaneous administration of anesthetic agents results in prolonged and unreliable induction times.

Although a renal portal system has been identified in reptiles, the pharmacokinetics of injectable agents have been shown to be minimally altered if injected into the caudal half of the body.

In snakes, IM injections are given into the paravertebral muscles. IV injections can be given into the ventral coccygeal vein or the right jugular vein, after a cutdown procedure. Intracardiac injections should only be given in emergency situations for administration of emergency drugs. In lizards and chelonians, IM injections can be administered into the musculature of the front limbs. In chelonians, the jugular vein can be catheterized for IV access or the coccygeal vein can be used for IV injections. In most lizards, the ventral coccygeal vein is used for IV drug administration. Lizards have a prominent ventral abdominal vein that can be catheterized for administration of anesthetic agents such as propofol and for administration of effective fluid therapy during anesthesia. In patients in which venous access is difficult, an 10 catheter can be placed anterograde into the tibia.

LOCAL ANESTHETIC AGENTS

Local anesthetic agents alone are not routinely used in reptiles. However, they can be used for the same indications as in domestic animals.26 As part of a balanced analgesic regimen, local anesthetic agents such as lidocaine or the longer-acting bupivacaine should be administered concurrently with systemic analgesic agents. Techniques for local and regional anesthesia, including epidural anesthesia, have not been described in reptiles. However, indications for use of local anesthetic techniques are similar to those in domestic animals. Intercostal nerve blocks and interpleural administration of local anesthetic agents are indicated for coeliotomies in reptiles. The most effective local anesthetic agent is bupivacaine at 1 to 2 mg/kg. Administration of bupivacaine should be repeated every 4 to 12 hours if the patient tolerates it. Additional indications for the application of local anesthetic agents in reptiles include orthopedic surgeries in combination with systemic analgesic agents.

INHALATIONAL AGENTS

Most anesthetic regimens in reptiles are based on the administration of inhalational agents either alone or in combination with parenteral agents such as dissociative agents, benzodiazepines, opioid agents, and alpha₂-agonists. Inhalational agents can be administered for both induction and maintenance of anesthesia in most reptile species. Inhalational agents should be administered with a precision vaporizer in oxygen, and a nonrebreathing system is indicated in most smaller reptile species (<10 kg body weight). Induction and maintenance requirements of the inhalational agent are determined by the health status of the animal and the amount of preanesthetic agent administered.

At present, the inhalational agent of choice in reptiles is isoflurane because of its rapid induction and recovery times, minimal depressant effects on cardiopulmonary function, and limited hepatic and renal toxicity. For most reptile species, isoflurane concentrations for induction of anesthesia are 5% and maintenance requirements range between 2% and 3%. In Green Iguanas, the minimum alveolar concentration (MAC) of isoflurane has been determined at 2.1%. Lower concentrations are indicated for severely debilitated patients.

Sevoflurane, commonly used in human and domestic animal anesthesia, has been investigated in several reptile species with various results. Sevoflurane has a low solubility in blood, which results in short induction and recovery times and the ability to rapidly change the depth of anesthesia. During induction with sevoflurane, a rapid increase in alveolar concentration can be seen. In humans and domestic animals, use of premedicants does not change the concentration of sevoflurane necessary for induction of anesthesia. In reptiles, induction times with sevoflurane appear to vary between species, and some species may fail to reach a surgical plane of anesthesia, even at high concentrations.

A study in Desert Tortoises showed minimal cardiopulmonary depressant effects of sevoflurane. A study in Green Iguanas that compared anesthetic and cardiopulmonary effects of sevoflurane and isoflurane after premeditation with IM butorphanol (2 mg/kg) showed faster induction and recovery times and improved muscle relaxation with sevoflurane when compared with isoflurane. In sevoflurane-anesthetized iguanas, no significant changes in heart rate were seen over time; however, isoflurane-anesthetized iguanas had significantly lower heart rates approximately 30 minutes after induction of anesthesia. No significant differences between both agents were determined regarding their cardiopulmonary effects. If the agent is used alone, most reptile species need sevoflurane concentrations of 7% to 8% for induction and 3.5% to 4.5% for maintenance of a surgical plane of anesthesia.

INDUCTION OF ANESTHESIA

Techniques for induction of anesthesia depend on the species to be anesthetized, the procedure to be performed, and the health status of the patient. For most reptile species, recommendation is administration of a sedative agent (e.g., butorphanol or buprenorphine) before induction to reduce the amount of induction agent necessary and to decrease the likelihood of breath-holding and struggling. In patients in which vascular access has been established, propofol (3 to 5 mg/kg IV/10) is the induction agent of choice to facilitate endotrachael intubation and maintenance with an inhalational agent. The amount of injectable or inhalational agent necessary for induction of anesthesia depends on the type and dosage of the premedicant, the degree of sedation at the time of induction, and the condition of the reptile and should be adjusted accordingly.

Chelonians

Induction of anesthesia can be challenging in large tortoise species and aquatic species, with the latter often being aggressive and capable of delivering a painful bite. In large tortoises, gaining access to the head and the limbs once retracted into the shell is often difficult. Administration of inhalational agents alone via face mask may result in prolonged induction times, especially in aquatic species capable of prolonged breath-holding. In most species, administration of an injectable anesthetic agent facilitates handling and reduces the amount of induction agent necessary for induction of anesthesia (Figure 27-3). If a peripheral vein is accessible, the author prefers administration of propofol for induction of anesthesia after premeditation with IM butorphanol (1 to 2 mg/kg; Figure 27-4). Propofol (3 to 5 mg/kg) can be administered slowly to effect into the jugular vein or the coccygeal vein in most chelonians. In patients where IV access has not been established, IM administration of immobilizing agents is indicated. Ketamine, if given alone for immobilization, requires high dosages, resulting in prolonged recovery times and poor analgesia and muscle relaxation. A combination of ketamine (4 to 10 mg/kg), butorphanol (0.5 to 1 mg/kg), and medetomidine (40 to 150 µg/kg) administered intramuscularly facilitates handling and often allows endotracheal intubation and maintenance of anesthesia with isoflurane or sevoflurane.

Anesthesia was effectively and safely induced in a Loggerhead Seaturtle (Caretta caretta) with IV ketamine (5 mg/kg) and medetomidine (0.05 mg/kg) and maintained with sevoflurane (0.5% to 2.5%) In Snapping Turtles (Chelydra serpentina), a combination of ketamine (20 to 40 mg/kg IM) and midazolam (2 mg/kg IM) resulted in good sedation to facilitate handling. A combination of alphaxalon/ alphadolon (24 mg/kg) administered intracoelomically resulted in excellent muscle relaxation and a surgical plane of anesthesia in Red-eared Sliders (Trachemus scripta elegans).

Rocuronium, a reversible neuromuscular blocking agent, has successfully been investigated in Gulf Coast Box Turtles (Terrapene Carolina major) to induce short-term immobilization and facilitate endotracheal intubation. Turtles administered rocuronium at 0.25 to 0.5 mg/kg were effectively immobilized and the trachea was intubated. Reversal of the effects of rocuronium was via administration of neostigmine and glycopyrrolate. Any animal immobilized with a neuromuscular blocking agent is not anesthetized, and no analgesia is provided. Therefore, the length of the procedure should be minimized, and no painful invasive procedures should be performed without prior administration of effective anesthetic and analgesic agents.

Snakes

Most snakes can be premedicated with butorphanol (1 to 4 mg/kg IM) or a low dose of ketamine (5 to 20 mg/kg IM) before induction with an inhalational agent (e.g., 5% isoflurane or 8% sevoflurane). Large snakes such as boid snakes can be premedicated with Telazol (2 to 4 mg/kg IM) to facilitate handling, endotracheal intubation, and induction with an inhalational agent. For IV administration of the induction agent, propofol should be administered into the ventral tail vein. Venomous snakes can be induced in an induction chamber or directly intubated and maintained with an inhalational anesthetic agent. Clear plexiglass tubes are ideal for handling of venomous snakes. They allow safe restraint and visualization of the snake, and tubes are often provided with small holes and slits to allow injections and sample collection. Once the snake is restrained in the tube, an inhalant anesthetic can be administered into the tube to faciliate induction of anesthesia and endotracheal intubation.

Lizards

Most lizards can deliver a painful bite to the inexperienced handler, and one should be aware of the tail and the nails that can inflict injury. The use of leather gloves is recommended for handling large powerful lizard species. Large potentially dangerous lizards can be administered tiletamine-zolazepam (4 to 6 mg/kg IM) to facilitate handling. Butorphanol (1 to 4 mg/kg IM) administered 30 minutes before induction is useful as a preanesthetic and provides preoperative and intraoperative analgesia. Butorphanol alone often does not produce pronounced sedative effects but does reduce the amount of induction agent necessary to induce anesthesia. If venous access is available, propofol (3 to 5 mg/kg IV) administered to effect induces anesthesia to facilitate endotracheal intubation and maintenance with the inhalational anesthetic agents isoflurane or sevoflurane.

The ventral coccygeal vein and the ventral abdominal vein are the preferred venous access sites. Access to the cephalic vein requires a cut-down procedure in most lizards. If inhalational agents are selected for induction of anesthesia, lizards can be induced via facemask with isoflurane (4 % to 5%) or sevoflurane (7% to 8%).

Crocodilians

All crocodilians should be considered dangerous and should only be handled by experienced handlers. A variety of injectable agents have been investigated for chemical restraint of crocodilians with variable success.33-ss Apparent species differences in response to immobilizing agents have been observed in crocodilians. Most anesthetic regimens for crocodilians are based on injectable agents to provide immobilization and safe handling and faciliate induction and maintenance of anesthesia with inhalational agents. Muscle relaxants (e.g., gallamine and succinylcholine) either alone or in combination with other agents (e.g., benzodiazepines, ketamine) have been used in crocodilians to provide immobilization.

Potent opioid agents such as etorphine HCl have been investigated in a variety of crocodilian species. In comparison with mammalian species, crocodilians need higher dosages to induce immobilization, often in exceess of 1 mg/kg IM. For small crocodilians that can be manually restrained, propofol (3 to 5 mg/kg IV) is the induction agent of choice and should be given into the ventral coccygeal vein. After induction, the animal should be intubated and maintained on an inhalational agent. Large crocodilians require administration of IM anesthetic agents for safe handling. Tiletamine-zolazepam (5 to 10 mg/kg IM) often provides sufficient immobilization to facilitate handling and endotracheal intubation. However, recovery times after tiletamine-zolazepam administration may be prolonged. A combination of ketamine (5 to 20 mg/kg 1M) and medetomidine (80 to 360 µg/kg IM) induced effective and reversible anesthesia in American Alligators (Alligator mississippiensis). Reversal with atipamezole was rapid and complete.

Endotracheal Intubation

Endotrachael intubation after induction of anesthesia is relatively easy to perform in most reptile species and is recommended in all patients to maintain a patent airway, prevent aspiration of fluids (e.g., during oral surgery), and allow positive pressure ventilation during maintenance of anesthesia.

The glottis is located rostrally in snakes and in carnivorous lizards. Herbivorous lizards and chelonians have a fleshy tongue, and the glottis is located at the base. For visualization of the tracheal opening, adequate jaw relaxation should be present. A laryngoscope blade and a light source aid in the visualization of the glottis. Chelonians have a relatively short trachea, and care should be taken not to intubate one bronchus. An adequately sized uncuffed endotracheal tube is recommended for most reptiles to avoid damage to the tracheal mucosa that could result in ischemic injury. In oral surgical procedures, cuffed endotracheal tubes can be used, but care should be taken not to overinflate the cuff. Therefore, large-volume low-pressure cuffs are preferable over low volume high-pressure cuffs. For minimization of the potential for overinflation of the cuff, a small syringe should be used for inflation. In respiratory emergencies, such as obstructive processes in the oral cavity or the trachea (e.g., granulomas, foreign bodies), a tracheostomy can be performed to gain access to the trachea and secure an airway.

MAINTENANCE AND MONITORING

All anesthetic agents have cardiopulmonary depressant effects, and during maintenance of anesthesia, cardiopulmonary performance should be closely monitored. Minimally, rate and depth of respiration and heart rate should be recorded. Supportive care during maintenance of anesthesia includes adequate fluid therapy on the basis of laboratory findings. For correction of major fluid deficits and for maintenance fluid therapy, IV or 10 administration of fluids is most effective. In small reptile species, commercially available syringe pumps are mandatory to deliver accurate fluid volumes at a constant rate. The rate of fluid administration depends on the degree of dehydration. In critical cases, a venous blood sample can be collected during anesthesia to monitor success of fluid therapy and initiate corrective measures if indicated. For maintenance fluid requirements, 5 to 10 mL/kg/h of a balanced electrolyte solution is recommended. Also recommended is monitoring of blood parameters such as PCV, hemoglobin, total protein, glucose, and electrolytes during anesthesia and at regular intervals into the recovery period.

During the anesthetic event, the reptile should be maintained within the POTR. Supplemental heat can effectively be provided via heating blankets and heat lamps. During surgery, the reptile should be frequently assessed for effective analgesia. If signs of pain are present during anesthesia and surgery, such as movement or increase in heart and respiratory rate in response to a painful stimulus, the analgesic protocol should be reviewed and additional analgesic agents should be administered during surgery. Critical assessment of the following parameters is recommended for effective anesthetic monitoring of the reptilian patient.

Reflexes

In reptiles, muscular tone and reflexes are evaluated for assessment of anesthetic depth, and the presence or absence of reflexes should be recorded. During a surgical plane of anesthesia, the righting reflex is absent as is the palpebral reflex in chelonians and most lizard species. The corneal reflex should be present; its absence indicates a deep plane of anesthesia. In some lizard species and in all snakes, the palpebral and corneal reflexes cannot be evaluated because of the presence of the spectacle. Additional reflexes to be monitored include the tail, toe, and cloacal reflexes. If no response is found to a surgical stimulus, the anesthetic depth should be critically evaluated to ensure the patient's condition is not too deep. If the reptile is in a surgical plane of anesthesia, slight movement in response to a stimulus is normally not associated with the perception of pain.

Cardiovascular Performance

The most useful monitoring equipment is a Doppler flow device with the probe positioned at the level of the heart (snakes and lizards) or over the carotid artery (chelonians and lizards) to monitor heart rate and rhythm. The probe can also be placed over the coccygeal artery in lizards and snakes. In chelonians, a pencil probe should be placed at the level of the thoracic inlet, close to the heart and the major vessels.

Electrocardiography (ECG) is a useful monitoring tool for detection of changes in heart rate, such as tachycardia and bradycardia and arrhythmias; however, it does not determine mechanical performance of the heart. ECGs can be recorded with leads attached in a conventional manner. ECGs should especially be recorded in reptiles suspected of or diagnosed with cardiac disease or when arrhythmias are detected during routine monitoring.

Direct arterial blood pressure measurements are the most accurate tool for continuous assessment of arterial blood pressure. However, they are impractical in most reptile patients because of the limited access to a peripheral artery. In most cases, a cut-down procedure is necessary to gain access to the femoral or carotid artery. In those lizard and chelonian patients in which arterial catheterization is necessary, the left carotid artery is the most accessible artery.

Respiratory Performance

During a surgical plane of anesthesia, all reptiles exhibit respiratory depression characterized by bradypnea or even apnea. Consequently, all reptiles need assisted ventilation or intermittent positive pressure ventilation (IPPV) during anesthesia, either manually or via mechanical ventilators (Figures 27-5 and 27-6). Little work has been published on effective and safe ventilation in anesthetized reptiles. The general principles of IPPV should also be applied in reptilian patients. Manual ventilation can be effectively administered to reptiles, however, it is labor intensive and allows less control of tidal volume and peak airway pressure. Small animal ventilators, pressure driven or volume driven, are commercially available and can be used for reptiles. The tidal volume and respiratory rate determine minute ventilation and in most healthy mammals a tidal volume of 20 mL/kg at a respiratory rate of 10 breaths/minute is adequate to maintain a normal PaC0₂.

However, the tidal volume of reptiles is larger than that of mammals of comparable body mass, and the rate of IPPV is usually set between 4 and 8 breaths/minute. Peak airway pressure should not exceed 10 to 15 cm H20 and inspiration should not take longer than 1 to 2 seconds. In order to minimize the negative effects of IPPV on cardiovascular performance (e.g., hypotension, decreased cardiac output) the lowest pressure and inspiration time necessary to ensure appropriate ventilation should be used. In reptiles, a useful visual aid for delivery of an adequate tidal volume is also observation of chest expansion during inspiration.

In human and domestic animal anesthesia, pulse oximetry is a useful tool for monitoring heart rate and trends in relative arterial oxygen saturation (SpO₂) and detecting hypoxemia (Sp0₂ <>

Arterial blood gas analysis is impractical in most reptiles, and a cut-down procedure is necessary in most patients to gain arterial access. In addition, the size of the reptile is often the limiting factor in catheterization of a peripheral artery for arterial blood gas determination. Arterial blood gas analyzers directly measure PaO₂ PaCO2, and pH, and these values can be interpreted as absolute numbers. Arterial blood oxygen saturation (SaO), however, is calculated on the basis of the human oxygen hemoglobin dissociation curve. Cardiac sampling for blood gas analysis is inaccurate in reptiles because of the mixture of arterial and venous blood within the ventricle. Venous blood gas analysis is of very limited value for assessment of pulmonary function in reptiles.

End-tidal PCOZ monitoring has become the standard in human anesthesia for determination of respiratory performance and estimation of PaCO₂. Capnometry measures CO₂ concentrations in the expired air for determination of adequate ventilation. Analyzers with high sampling rates (>100 mL/minute) are unsuitable for small reptiles; however, analyzers with low sampling rates of 50 mL /minute and less are available and are more suitable for most reptiles. End tidal CO₂ monitoring in reptiles is limited by the fact that reptiles can develop cardiac shunts. A report in Green Iguanas concluded that no correlation exists between end-tidal CO₂ concentrations and arterial PCO₂ values. However, changes in end-tidal CO₂ may give valuable information on existing complications. A decrease in end-tidal CO₂ may indicate airway leaks, airway obstruction, disconnection of the reptile from the breathing system, or if IPPV is used, malfunction of the ventilator.

RECOVERY AND POSTOPERATIVE CARE

Recovery of the reptilian patient should be in a temperaturecontrolled and humidity-controlled environment that closely resembles the natural requirements of the species. Small animal incubators are ideal for this purpose, and most offer the ability to provide supplemental oxygen, if indicated (Figure 27-8). The reptile should only be extubated when oral and pharyngeal reflexes have returned and the animal is breathing spontaneously.

Throughout the recovery period, cardiopulmonary parameters, including heart rate and respiratory rate and pattern, should be frequently monitored and recorded. If indicated, respiratory support such as IPPV with room air should be administered. In reptiles, low oxygen concentrations are the stimulus to breath and high oxygen concentrations in the inspired air may prolong return to spontaneous respiration. In a study with Green Iguanas, patients were found to recover twice as quickly when breathing only room air as compared with those patients on supplemented with oxygen.

If supplemental oxygen is necessary, facemasks are most useful and the flow rate of oxygen should be 2 to 5 L / minute, depending on the size of the patient. Insufflation of oxygen can be achieved with several techniques. For nasal insufflation with oxygen, a rubber catheter is inserted into the nares and then sutured or glued to the scales. Oxygen at a rate of 0.5 to 3 L/minute should be delivered through a humidifier to prevent drying of the airways. In reptiles with obstructive processes in the nasal passageways or the oral cavity, the trachea can be insufflated with oxygen. With this technique, a catheter is inserted percutaneously into the trachea with the tip advanced to the bifurcation.

Throughout the recovery period, the absence or presence of reflexes, such as palpebral, corneal, foot, and tail withdrawal reflexes, should be recorded in regular intervals for assessment of the degree of recovery and return to a preanesthetic state. Adequate fluid therapy should be continued into the recovery period to ensure normovolemia of the patient. Balanced electrolyte solutions are recommended for most species, and if indicated, determination of hematologic and plasma biochemical parameters facilitates accurate assessment of effective fluid therapy. For reduction of recovery time, increase in environmental temperature during the recovery period above the POTR for the species is not recommended. Increases in environmental temperature result in increased metabolism and consequently an increased demand for oxygen by the tissues. During recovery, most reptiles have respiratory depression and may not be able to meet the increased oxygen demand.

Reptiles recovering from anesthesia should be monitored closely for any evidence of postoperative distress or pain. The analgesic regimen should be reevaluated in reptiles with signs of discomfort or pain. If indicated, additional analgesic agents should be administered in the postoperative period.

Only fully recovered animals should be returned to their enclosure, especially if they are housed in groups, to avoid potential injuries from cage mates. Aquatic species should only be returned back to their aquatic environment completely recovered to prevent accidental drowning.

ANALGESIA

Current knowledge of effective analgesic drugs and therapy in reptiles is scant (Table 27-2). Few studies have evaluated effective pain management in common reptile species. Unfortunately, lack of knowledge of effective drugs and dosage regimen often results in neglecting the management of pain in reptilian patients. A recent study concluded that provision of analgesia for the reptilian patient is uncommon. However, all vertebrates experience pain, and the major difference between reptiles and mammalian species may be different pain pathways and receptors. Reptiles posess an endogenous opioid system, and nociceptive neurns in crotaline snakes are similar to those identified in monkeys.40

In some cases, lack of recognition of pain in reptiles and unfamiliarity with analgesic agents may result in improper pain management. Conditions such as trauma, neoplasia, surgical procedures, and chronic disease processes commonly associated with pain in humans and mammals also cause pain and discomfort in reptiles.

Before treatment, familiarity with the reptile species is mandatory, including knowledge of normal behavior and signs that indicate discomfort and pain, such as restlessness, increased respiratory rate, anorexia, and aggressiveness. Assessment of pain and the required analgesic regimen is mandatory before treatment. The physiology and pathophysiology of pain have been described in detail elsewere.

Pain, stress, and discomfort are closely related, and effective pain management greatly reduces stress and discomfort of the reptile, thus reducing or eliminating the effects of acute and chronic pain on the animal's metabolism, such as compromised immune function, hematologic and biochemical imbalances, and metabolic changes. Although most veterinary practitioners are familiar with "normal" behavior in domestic animals such as dogs and cats, recognition of normal and abnormal behavior is often challenging in reptiles. Although the reptilian patient does not show obvious well-recognized signs of pain such as vocalization it does not mean the animal does not experience pain and discomfort. However, familiarity with normal behavior and normal body position may help in the diagnosis of pain. Abnormal body position in reptiles, such as hunched-up abdomen or resting in an abnormal position, reluctance to lie down in lizards and tortoises, and abnormal movement such as abnormal gait and restlessness may indicate discomfort. Additional signs in reptiles include anorexia, increased aggressiveness, depression, trembling, and increased respiratory rate as

Analgesic regimens in reptiles are often adjusted from the pharmacokinetic and pharmacodynamic principles known from domestic animals. For effective analgesia and comfort for the reptile, acute pain needs to be differentiated from chronic pain. Acute pain is the result of trauma, surgery, or an infectious event and is of relatively short duration; chronic pain persists beyond an acute injury and has severe effects on metabolic status. Chronic pain such as cancer pain and arthritis serves no biologic function and often results in severe impairment and distress of the animal.

Prevention of pain is the most effective method of pain management. Therefore, preemptive analgesic techniques are recommended in cases in which the animal undergoes elective surgical procedures. Similar to domestic animals, balanced analgesic techniques are most effective in the treatment of intraoperative and postoperative pain in reptiles. Often this includes administration of systemic analgesic agents (opioid agents) in combination with long-acting local anesthetic agents (e.g., bupivacaine).

Acute Pain Management

Opioid agents such as butorphanol and buprenorphine are most often used for the management of acute pain in reptiles. Indications for the treatment of acute pain include traumatic events such as shell fractures in chelonians; fractures of the long bones in lizards; bite wounds; thermal burns from default heating devices, especially in snakes and lizards; and surgical procedures such as coeliotomies. The latter are commonly performed in reptiles for removal of masses, such as granulomas and neoplasia; reproductive surgeries; and removal of bladder stones. Although effective drugs and dosage intervals are poorly understood in reptiles, the patient should be frequently assessed for evidence of pain, especially in the postoperative period. Recognition of signs of pain and, discomfort often facilitates effective analgesic therapy.

Local Anesthetic Agents

In reptiles, local anesthetics are often used for local procedures, such as surgical debridement of abscesses. For invasive procedures, administration of local anesthetic agents should be accompanied by concurrent administration of systemic analgesic agents such as opioid agents as part of a preemptive analgesic regimen. Both lidocaine and bupivacaine can be used in reptiles; the former has a fast onset of action, and the latter is more effective in controlling postoperative pain because of its long duration of action. Many techniques have described in domestic animals the use of local anesthetics to provide topical and regional anesthesia and local infiltration techniques and field blocks. These techniques are often directly applicable to reptiles. Local anesthetics can be directly applied to surgical wounds (e.g., abscess debridement) or injected into coeliotomy incisions in the reptiles. Although toxic doses of both drugs have not been determined in reptiles, one should not exceed 4 mg/kg bupivacaine and 10 mg/kg lidocaine in reptiles to avoid potential side effects such as arrhythmias and seizures.

Chronic Pain Management

Chronic pain management in reptiles is often neglected because of a poor understanding of the effects of drugs used for the management of chronic pain in domestic animals, especially nonsteroidal antiinflammatory agents (NSAIDs). Various metabolic bone diseases, gout, renal disease, and a variety of neoplastic diseases are a few examples of conditions associated with chronic pain in reptiles. NSAIDs can be used for the management of chronic pain in reptiles, although little information is available regarding effective treatment regimens and potential side effects in reptiles. NSAIDs offer the advantage of a long duration of action, and both ketoprofen and carprofen are useful analgesic agents for the reptilian patient diagnosed with chronic pain. Before administration of these agents, every effort should be made to determine the renal status of the patient because both drugs should not be used in patients with severe renal and gastrointestinal disease.

Agent	Dosage (mg/kg)	Route	Frequency	Comments
Bupivacaine	1-2	Local infiltration	4-12 h	Maximum dose: 4 mg/kg
Buprenorphine	0.02-0.2	SC, IM	12-24 h	All species
Butorphanol	0.4-2.0	SC, IM,IV	12-24 h	All species
Carprofen	1-4	PO, SC, IM, IV	24 h	All species
Flunixin meglumine	0.5-2	IM	12-24 h	All species
Ketoprofen	2	SC, IM	24 h	All species
Lidocaine	2-5	Topical and local infiltration	-	Maximum dose: 10 mg/kg
Meloxicam	0.1-0.2	PO	24 h	All species
Morphine	0.4-2.0	SC, IM	12h	Species variability
Oxymorphone	0.1-0.2	SC, IM	12-24 h	Species variability