INJECTABLE ANESTHESIA IN SOUTH AMERICAN CAMELIDS

Thomas Riebold DVM, Diplomate ACVAA Veterinary Teaching Hospital College of Veterinary Medicine Oregon State University Corvallis, Oregon 97331

INTRODUCTION

Interest in llamas, and more recently in alpacas, as pets and as breeding and pack animals has led to increased demand for veterinary services for them. While they have some unique species characteristics regarding anesthesia, many of the principles and techniques used in food animal and equine anesthesia also apply to South American camelids. Except for differences in size, anesthetic management of alpacas and llamas is similar. Much like there are species differences between cattle, sheep, and goats in their response to xylazine, it does appear that alpacas require higher doses of sedatives, approximately 10-20%, to obtain the same response that lower doses of sedatives would obtain in llamas.

PREANESTHETIC CONSIDERATIONS

Consideration for preanesthetic preparation includes fasting, assessment of hematologic and blood chemistry values, venous catheterization, and estimation of bodyweight. The camelid has a stomach divided into three compartments. Therefore, potential complications similar to those of domestic ruminants, regurgitation and aspiration pneumonia, exist during anesthesia. Abdominal tympany as it occurs in anesthetized domestic ruminants does not appear to occur in anesthetized camelids. It is recommended that the animals be fasted 12-18 hours and deprived of water for 8-12 hours. In nonelective cases, this is often not possible and precautions should be taken to avoid aspiration of gastric fluid and ingesta. Fasting neonatal camelids is not advisable because hypoglycemia may result. As in other species, hematologic and blood chemistry values are determined before anesthesia. Results should be compared to reference values.

Venipuncture and venous catheterization are often performed in camelids. Physical restraint during venipuncture or catheterization varies and can consist of a handler holding the camelid's halter, and if the camelid is fractious, grasping an ear; or it can involve use of restraining chutes designed specifically for camelids. Bending the neck excessively to either side seems to hinder venipuncture and catheter placement and increase the likelihood of entering the carotid artery. Local anesthesia at the catheterization site is recommended for catheter placement.

The jugular vein is formed rostrally by the union of the linguofacial vein ventrally and maxillary vein dorsally and in that aspect is comparable to the external jugular vein of domestic mammals. However, rather than taking a superficial course in the neck, the vein is directed deeply in its caudal course for most of its length and is contained in the carotid sheath with the common carotid artery and vagosympathetic nerve trunk in a relationship similar to the internal jugular vein of horses and domestic ruminants.

Most of the jugular vein lies deep to the sternomandibularis and brachiocephalicus muscles, ventral to cervical vertebral transverse processes. Beginning at a point about 15 cm caudal to the ramus of the mandible, the rostral course of the jugular vein is separated from the carotid artery by the omohyoideus muscle. The origin of the jugular vein is located at the intersection of a line drawn caudally along the ventral aspect of the body of the mandible and another line connecting the base of the ear and the lateral aspect of the cervical transverse processes. Venipuncture or catheterization can be performed at the bifurcation of the jugular vein or at any point caudal to it. Because of the close proximity of the carotid artery to the jugular vein, one must ascertain that the vein has been catheterized and not the artery before injecting any medication.

Camelids have a round neck without a distinct jugular groove. The location of the jugular vein can be approximated by placing the four fingers of one's hand at the dorsal midline of the neck and pressing the thumb against the cervical vertebrae. After occlusion of the vessel, one will usually be unable to see the jugular vein distend; however, the vein can be palpated or balloted particularly rostrally and more easily in females and altered males because their skin is thinner. On occasion, one will be able to see the jugular vein of crias and juvenile camelids distend. Sixteen gauge catheters are appropriate for adult camelids and 18-20 gauge catheters for smaller camelids. Camelids can have 4-5 jugular venous valves that prevent flow of venous blood into the head when the head is lowered during grazing. Contact of the catheter tip with jugular venous valves while threading it may prevent successful catheterization; a site caudal to the point where the valve was contacted should be used.

Administration of small volumes of drugs can also be made through an ear vein of tractable camelids without too much of a vigorous response from the animal. Use of small gauge needles (25 ga) is recommended. Clipping the area is helpful to improve visibility of the vessel. The vessels are small and the back wall of the vessel is often flattened by the auricular cartilage making the lumen smaller than one would expect. If one wishes to place a catheter in this vessel, it is useful to block the area with lidocaine at the base of the ear. Injection in the caudal auricular artery must be avoided. Injection of drug preparations with pH values widely different from physiological pH, for example, phenylbutazone, must be avoided to prevent thrombophlebitis and risk of ear slough.

Finally, bodyweight of the camelid must be determined either by weighing the animal or estimating its weight so that accurate drug administration is possible. It is easy to overestimate bodyweight because camelids, particularly llamas, are fairly tall animals and have a long haircoat that obscures their body type. Adult male llamas usually weigh from 125-160 kg although occasional males can exceed 180 kg. Adult female llamas usually weigh from 100-150 kg but occasional females will also exceed 180 kg. Adult male alpacas usually weigh from 55-80 kg and adult female alpacas usually weigh from 45-70 kg. Bodyweight of crias and small juveniles may be estimated by lifting the individual or a bathroom scale can be used to determine weight by weighing an individual while holding the camelid and without it.

2 SEDATION/RESTRAINT

Although acepromazine is not commonly used in llamas and alpacas, it has been used at 0.03 mg/kg. Acepromazine should be expected to produce actions similar to those produced in domestic ruminants. Recumbency usually does not occur. Acepromazine and other phenothiazine derivative tranquilizers are contraindicated in anemic, cachexic or debilitated animals and animals with compromised cardiovascular status.

Xylazine is often used to provide sedation or, in higher doses, restraint. Although complete data are not available on the cardiovascular and respiratory effects of xylazine in camelids, the agent causes bradycardia as it does in other species and probably causes mild hypertension or has little effect initially on blood pressure followed by mild hypotension. The degree of sedation or restraint that results depends on the amount given and the animal's temperament. Poorly trained animals or berserk males tend to be less responsive and ill or debilitated camelids are more responsive to sedatives. Low doses (0.1 mg/kg IV or 0.15-0.2 mg/kg IM, llamas; 0.015 mg/kg IV, 0.2-0.3 mg/kg IM, alpacas) provide sedation without recumbency. Butorphanol (0.07-0.1 mg/kg IV or IM) can also be used to provide sedation and analgesia in camelids. While butorphanol does provide sedation, it also causes some degree of dysphoria in camelids yielding sedation that is qualitatively somewhat less than that usually obtained with tranquilizers and sedatives. The animals usually remain standing but may show slight agitation.

Higher doses of xylazine will cause recumbency and light planes of general anesthesia. Xylazine, 0.3 mg/kg IV (llamas), 0.4 mg/kg IV (alpacas), usually produces 20 to 30 minutes of recumbency in llamas. Xylazine can also be given intramuscularly at 0.44-0.66 mg/kg (llamas) or at 0.66-0.88 mg/kg (alpacas) to produce recumbency. Higher doses of xylazine, 0.5 mg/kg IV in llamas, can provide sufficient sedation and restraint to allow tracheal intubation. Even though intubation may be possible, muscle relaxation is poor and intubation can be difficult.

In a limited number of llamas, detomidine in doses as high as 40 ìg/kg IV provided mild sedation but would not provide restraint in llamas. The animals would lie down following detomidine administration but would arise as soon as a handler approached.

Medetomidine has recently been evaluated for use as a sedative/restraint agent in llamas. Doses as low as 10 ìg/kg IM give brief periods of standing sedation (approximately 35 minutes). Onset of sedation is approximately 10-15 minutes. Llamas will not always assume sternal recumbency and, if they do so, duration is brief (5-10 minutes). Analgesia is not present. When medetomidine is given at 20 ìg/kg IM sedation is more profound and lasts approximately 60 minutes. Onset of sedation is approximately 10-15 minutes. Llamas will assume either sternal or lateral recumbency. Analgesia is present about 30 minutes following injection and lasts approximately 30 minutes. When medetomidine is given at 30 ìg/kg IM onset of sedation is within 7 minutes and sedation is more profound. Duration of recumbency approaches two hours. Llamas will assume either sternal or lateral recumbency. Analgesia is present about 15 minutes following injection and lasts

3 Agent Dose Duration Comment

Butorphanol 0.07 - 0.1 mg/kg IM 30 - 45 minutes Provides standing sedation without recumbency

Xylazine 0.1 mg/kg IV 30 - 45 minutes Provides standing sedation without recumbency. Can be (llamas) 0.15-0.2 mg/kg IM reversed with atipamezole (30 ìg/kg IV), tolazoline (1.0 mg/kg IV), or yohimbine (0.12 mg/kg IV).

Xylazine 0.15 mg/kg IV 30 - 45 minutes Provides standing sedation without recumbency. Can be (alpacas) 0.2-0.3 mg/kg IM reversed with atipamezole, tolazoline or yohimbine.

Medetomidine 10 µg/kg IM 5 - 10 minutes Provides standing sedation without recumbency Can be reversed with atipamezole, tolazoline, or yohimbine

Midazolam 0.5 mg/kg IM up to 100 minutes Provides mild standing sedation.

Table 1. Doses of injectable anesthetic agents commonly used for standing sedation in camelids. approximately 60 minutes. As an alternative dexmedetomidine could be used at 0.5 of the medetomidine dose. Proprietary medetomidine is currently unavailable in the United States, having been replaced by dexmedetomidine, available in both 0.1 mg/ml and 0.5 mg/ml preparations. Medetomidine is available in Europe in two different concentrations, 1 mg/ml and 10 mg/ml. The more concentrated product is more convenient to use in large animals. In the United States an additional source of generic medetomidine is Wildlife Pharmaceuticals, Windsor, Colorado. They have preparations of medetomidine of 10 mg/ml, 20 mg/ml, and 40 mg/ml.

Use of romifidine has not been reported in South American camelids. Its effect have been reported in dromedary camels at 40 ìg/kg, 80 ìg/kg, and 120 ìg/kg IV. The lowest dose provides little to mild sedation lasting at approximately thirty minutes. Mild analgesia is present for 20 minutes. Given at 80 ìg/kg IV, romifidine provides mild to moderate sedation of approximately 50 minutes duration with analgesia present for 35 minutes. Given at 120 ìg/kg IV, romifidine causes recumbency and and marked sedation of approximately one hour duration with analgesia present for 45 minutes. Extrapolating to South American camelids, a dose of approximately 60-80 ìg/kg IV would seem logical for mild to moderate sedation. When restraint is needed then 120 ìg/kg IV could be given although its duration of action may be longer than that obtained with administration of xylazine to South American camelids and may limit its applicability.

The benzodiazepines are usually ineffective sedative agents in most species and will cause excitement in some species. However, they can be effective in ruminants and South American camelids while causing relatively mild cardiovascular effects. Diazepam and midazolam are used interchangeably in most species. Because of its formulation, intramuscular administration of diazepam is not recommended. Midazolam is water soluble and can be given either intramuscularly or intravenously. Midazolam is given at 0.5 mg/kg IM to alpacas and provides sedation without recumbency of approximately 100 minutes duration. When given at 0.5 mg/kg IV to alpacas

4 Agent Dose Duration Comment

Xylazine (llamas) 0.3 mg/kg IV 30 - 45 minutes Will cause recumbency. Can be reversed with atipamezole 0.44 - 0.66 mg/kg IM (30 ìg/kg IV), tolazoline (1.0 mg/kg IV), or yohimbine (0.12 mg/kg IV).

Xylazine (alpacas) 0.4 mg/kg IV 30 - 45 minutes Will cause recumbency. Can be reversed with atipamezole 0.66 - 0.88 mg/kg IM (30 ìg/kg IV), tolazoline (1.0 mg/kg IV), or yohimbine (0.12 mg/kg IV).

Medetomidine 20 - 30 µg/kg IM 30 - 110 minutes Will cause recumbency. Can be reversed with atipamezole (30 ìg/kg IV), tolazoline (1.0 mg/kg IV), or yohimbine (0.12 mg/kg IV).

Midazolam 0.5 mg/kg IV up to 100 minutes Provides strong sedation and recumbency.

Xylazine 0.2 mg/kg IV 20 - 30 minutes Combined and given together. Provides recumbency and Butorphanol 0.02 - 0.04 mg/kg IV profound sedation.

Midazolam 0.1 mg/kg IV 20 - 30 minutes Combined and given together. Provides recumbency and Butorphanol 0.1 mg/kg IV profound sedation.

Xylazine - 0.4 mg/kg IM 15 - 20 minutes Relaxation may be inadequate for orotracheal intubation; Ketamine 4.0 mg/kg IM may require local anesthesia at the site. given simultaneously

Butorphanol - 1.0 ml (10 mg) 20 - 25 minutes “BKX” Ketamine - 10.0 ml (1 gm) (restraint) Given at 1 ml/23 kg IM (llamas). Xylazine 1.0 ml (100 mg) 50 minutes Given at 1 ml/18 kg IM (alpacas). (recumbency) May require local anesthesia at the site.

Xylazine - 0.22-0.33 mg/kg IV 15 - 20 minutes “Ketamine Stun” Ketamine - 0.22-0.33 mg/kg IV Can be extended with a partial dose of ketamine. May Butorphanol 0.08-0.11 mg/kg IV require local anesthesia at the site.

Xylazine - 0.22-0.55 mg/kg IM 45 minutes “Ketamine Stun” Ketamine - 0.22-0.55 mg/kg IM Can be extended with a partial dose of ketamine. May Butorphanol 0.08-0.11 mg/kg IM require local anesthesia at the site.

Xylazine - 0.35 mg/kg IM 30 - 60 minutes Relaxation may be inadequate for orotracheal intubation; Ketamine 5.0 - 8.0 mg/kg IM may require local anesthesia at the site, relatively large given 15 minutes apart injection volume.

Tiletamine - 2.0 mg/kg IM 60 minutes Use of acepromazine, butorphanol, or xylazine increases Zolazepam duration. May require local anesthesia at the site.

Tiletamine - 4.0 mg/kg IM 120 minutes Relaxation may be inadequate for orotracheal intubation; Zolazepam may require local anesthesia at the site.

Table 2. Doses of injectable anesthetic agents commonly used for restraint in camelids.

5 midazolam provides strong sedation with recumbency of approximately 100 minutes duration. Currently midazolam has the advantage of being less expensive than diazepam.

Neuroleptanalgesia (combinations of analgesic agents and tranquilizers or sedatives) has been used in llamas. Xylazine, 0.2 mg/kg IV, and butorphanol, 0.02-0.04 mg/kg IV, have been combined to provide recumbency and profound sedation. They can be combined and given or can be given simultaneously in separate syringes. Duration of action is approximately 20 minutes. When use of xylazine is contraindicated, midazolam, 0.1 mg IV, and butorphanol, 0.1 mg/kg IV, simultaneously provide restraint of short duration.

Xylazine, 0.25 mg/kg IV or 0.35 mg/kg IM, and ketamine, 3.0-5.0 mg/kg IV or 5.0-8.0 mg/kg IM 15 minutes later, usually provide 30-60 minutes of restraint. Xylazine, 0.4 mg/kg IM, and ketamine, 4.0 mg/kg IM, given simultaneously usually provide 15-20 minutes of restraint. Tiletamine- zolazepam, 2.0 mg/kg IM, can provide up to one hour of restraint. Duration of recumbency can be lengthened the addition of acepromazine, butorphanol, or xylazine. Tiletamine-zolazepam, 4.0 mg/kg IM, can provide up to two hours of restraint. Laryngeal reflexes were present but diminished following tiletamine-zolazepam affording some airway protection. Tiletamine-zolazepam used in this manner provides long duration of recumbency and probably other techniques that provide better airway management are better choices if up to two hours’ duration of effect is needed.

Combinations of butorphanol, xylazine, and ketamine (“BKX”) have also been used in camelids to provide restraint. The combination is prepared by adding 100 mg of xylazine (1 ml) and 10 mg butorphanol (1 ml) to 10 ml of ketamine. It is administered at 1 ml/18.8 kg IM to alpacas and at 1 ml/22.5 kg IM to llamas. Recumbency occurs within five minutes with duration of effect approximately 25 minutes. Other combinations of butorphanol, xylazine, and ketamine (“Ketamine Stun”) are also used. Given intravenously the combination is more predictable and is given at 0.22- 0.33 mg/kg xylazine, 0.22-0.33 mg/kg ketamine, and 0.08-0.11 mg/kg butorphanol. It will provide recumbency and analgesia for 15-20 minutes. Additional duration of action can be obtained by administration of a partial dose of ketamine. Given intramuscularly the combination is 0.22-0.55 mg/kg xylazine, 0.22-0.55 mg/kg ketamine, and 0.08-0.11 mg/kg butorphanol. Onset is within ten minutes and duration of action is approximately 45 minutes.

Amount of sedation/restraint varies with amount of the agents given, route of administration, and the camelid's temperament but is usually sufficient for minor procedures such as suturing lacerations, draining abscesses, or cast application. When these combinations provide insufficient anesthetic depth, supplemental local anesthesia may be needed to allow completion of surgery and intubation may not be possible. However, these combinations do immobilize the animal, facilitating venipuncture and administration of additional anesthetic agent or application of a face mask to increase depth of anesthesia and thus allow one to manage a fractious animal.

ALPHA2 ANTAGONISTS

6 Alpha2 agonist mediated sedation and recumbency in camelids can be reversed with alpha2 antagonists. Currently there are three alpha2 antagonists available for veterinary use. They are atipamezole (Antisedan,® 5 mg/ml, Zoetis), tolazoline (Tolazine,® 100 mg/ml, Lloyd Laboratories), ® and yohimbine (Yobine, 2 mg/ml, Lloyd Laboratories). Tolazoline has activity at both alpha1 and alpha2 receptors while the other two drugs are more selective having activity at only alpha2 receptor sites. Tolazoline is the only product available for equine use. The other drugs are available for canine use (Yobine® and Antisedan®) or compounded for use in exotic species. While the canine preparations could be used in large animal practice, the amount of yohimbine needed to reverse xylazine sedation could be costly in adult llamas, but less so in alpacas. Although doxapram, an analeptic, will reverse xylazine sedation in cattle and dogs it will not reverse xylazine sedation in camelids even when given in doses as high as 2.0 mg/kg IV. Currently these three alpha2 antagonists are also available from Wildlife Pharmaceuticals, a compounding pharmacy in Windsor, CO. They are atipamezole (10 mg/ml), tolazoline (200 mg/ml), and yohimbine (10 mg/ml).

Some general caveats about use of alpha2 antagonists are in order. Some agents, tolazoline, for example, cause vasodilatation because of their alpha1 effect. Caution should be exercised when tolazoline is given to animals with compromised cardiovascular status to avoid precipitating shock.

In these instances, atipamezole would be the better choice. Secondly, use of alpha2 antagonists to hasten recovery from alpha2 agonist / ketamine anesthesia can be inadvisable. If an alpha2 antagonist is administered before ketamine has been fully metabolized, recovery may be accompanied by more excitement because the excitatory effects of ketamine will be unmasked following antagonism of the sedative agent. Thirdly, given the differences between potency of alpha2 agonists, there may be some differences in response to alpha2 antagonist administration. That is, lower doses of antagonist may be sufficient to reverse xylazine sedation than would be used to reverse medetomidine sedation of the same duration.

The amount of alpha2 antagonist required to reverse an alpha2 sedative will depend on the amount of alpha2 agonist used and the interval between its administration and administration of the antagonist. If the interval between administration of the two drugs is relatively long, then extensive metabolism of the alpha2 sedative should have occurred and less antagonist will be needed. Giving the full dose of antagonist after extensive metabolism of the sedative has occurred could cause mild excitement and opisthotonus in the animal. Antagonists can be given either intramuscularly or intravenously. Often the drug is given intravenously in order to expedite reversal. If intramuscular administration is planned, a higher dose will be required and reversal will be more gradual.

When yohimbine is used in llamas at 0.12 mg/kg IV in combination with 4-aminopyridine at 0.3 mg/kg IV, it produced complete recovery from xylazine sedation. Its use singly in llamas is also effective and can be given at 0.12 mg/kg IV. If sufficient arousal does not occur, additional yohimbine can be given.

Atipamezole is also available for reversal of medetomidine and other alpha2 agonists. It is a highly selective alpha2 antagonist, approximately 200 times greater than yohimbine. Side effects associated with its use in unsedated dogs are increased heart rate, increased motor activity, irritability, panting,

7 sweating, and vomiting. Experience with atipamezole is somewhat limited in large animals. One could expect on occasion to see somewhat similar signs when reversing alpha2 sedation in large animals if large doses of atipamezole are given relatively long after the alpha2 sedative was administered. Atipamezole has been used in llamas at doses as high as 125 ìg/kg IV following medetomidine. Reversal of sedation occurred in approximately 6 minutes. In most instances, atipamezole at 30 ìg/kg IV is adequate to provide sufficient arousal following xylazine within five minutes.

Tolazoline appears to be more effective than yohimbine for reversal of xylazine sedation in domestic ruminants. This coupled with its availability as a large animal product, has led to its use in domestic ruminants and llamas. Unfortunately, there is considerable variation in dosage and toxicity between species with the dosage needed for reversal of xylazine in horses being quite high in relation to that needed to reverse xylazine sedation and restraint in domestic ruminants and llamas. It appears that tolazoline given at the equine dose in domestic ruminants and llamas can cause severe complications (transitory apnea, cardiac arrest, and, additionally in llamas, depression and vague signs of abdominal pain followed by death within twenty-four hours). Perhaps the acute complications are related to tolazoline's vasodilatory effect becoming more important in hypovolemic animals or they may be due to other unknown causes. Regardless of the mechanism, it is important to remember that tolazoline given in high doses has been associated with death following its administration to xylazine sedated llamas.

Our method of administering tolazoline to llamas and domestic ruminants has been to give 50% of the calculated dose (1.0 - 2.0 mg/kg IV) to effect initially and additional tolazoline if adequate reversal does not occur. In most instances, the initial amount (0.5 - 1.0 mg/kg IV) of tolazoline is adequate to provide sufficient arousal of the animal for it to be able to stand. Following tolazoline at the full calculated dose, 2.0 mg/kg IV as a bolus in llamas, opisthotonus can occur in some animals, usually those where the interval between alpha2 agonist and antagonist administration was longer. After that period of excitement subsides, recovery is uneventful. Tolazoline can also be given intramuscularly to produce more gradual reversal of alpha2 sedation.

GENERAL ANESTHESIA

Camelids tend to recover well from anesthesia without experiencing emergence delirium and are often not tranquilized prior to induction unless their temperament necessitates it or one wishes to use sedatives/analgesics as a component of the anesthetic protocol. Camelids are prone to parasympathetic discharge during intubation or painful stimuli during surgery. Atropine, 0.02 mg/kg IV or 0.04 mg/kg IM, is recommended to prevent bradyarrhythmia and will also decrease salivary secretions. If desired, glycopyrrolate, 5-10 ìg/kg IM or 2-5 ìg/kg mg/kg IV, could be substituted for atropine.

Induction can be accomplished in untranquilized camelids with several different techniques (Table 3) including thiobarbiturates (if available), 8.0-11.0 mg/kg IV; ketamine and xylazine, ketamine and

8 Agent Dose Duration Comment

Thiobarbiturate 8.0 - 11.0 mg/kg IV 10 - 15 minutes Relaxation adequate for intubation, may cause apnea

Xylazine - 0.25 mg/kg IV 30 - 45 minutes Relaxation usually adequate for intubation Ketamine 2.5 - 3.0 mg/kg IV 5 minutes apart

Xylazine - 0.5 mg/kg IM 15 - 20 minutes Relaxation usually adequate for intubation Ketamine 2.2 mg/kg IV give 5 minutes apart

Thiopental (0.2%) 4.4 mg/kg IV 15 - 20 minutes Good muscle relaxation Guaifenesin (5%) 100 mg/kg IV give combined to effect

Ketamine (0.1%) - 2.0 mg/kg IV 15 - 20 minutes Good muscle relaxation Guaifenesin (5%) 100 mg/kg IV give combined to effect

Diazepam (midazolam) - 0.11 - 0.22 mg/kg IV 5 - 15 minutes Relaxation usually adequate for orotracheal intubation Ketamine 4.4 mg/kg IV given simultaneously

Tiletamine - 2.2 mg/kg IV 30 minutes Relaxation may be inadequate for orotracheal intubation Zolazepam

Propofol 2.0 - 6.0 mg/kg IV 10 - 15 minutes Relaxation usually inadequate at lower doses for 0.4 mg/kg/min IV for orotracheal intubation of unsedated camelids. maintenance Recovery occurs approximately 30 minutes following discontinuation of infusion.

Alfaxalone 2.0 mg/kg IV 10 - 15 minutes Recovery is poor in unsedated camelids. Alfaxalone is (anesthesia) better used as an induction agent followed by inhalant 35 minutes anesthesia. (recumbency)

Xylazine (0.01 - 0.02%) Calculated infusion rate is Duration of anesthesia should be limited to 60 minutes. Ketamine (0.2%) 1.2 - 2.4 ml/kg/hr IV for Recovery occurs approximately 30 minutes following Guaifenesin (5%) maintenance of anesthesia. discontinuation of infusion.

Table 3. Doses of commonly used injectable induction agents in camelids.

diazepam or midazolam, 5% guaifenesin (50 mg/ml) and 0.2% thiobarbiturate (2 mg/ml) solution, 1.5-2.0 ml/kg IV to effect; 5% guaifenesin (50 mg/ml) and 0.1% ketamine (1 mg/ml) solution, 1.5- 2.0 ml/kg IV to effect; propofol (4-6 mg/kg IV), and tiletamine-zolazepam (2.2 mg/kg IV). Xylazine, 0.25 mg/kg IV, and ketamine, 2.5-3.0 mg/kg IV, may be administered 5 minutes apart to

9 obtain a more uniform response and sufficient depth of anesthesia for intubation when compared to intramuscular administration of xylazine - ketamine. If desired, xylazine, 0.5 mg/kg IM, followed by ketamine, 2.2 mg/kg IV, can be used. Duration of anesthesia is 15-20 minutes. Diazepam can be substituted for xylazine in debilitated animals and is given at 0.1 - 0.22 mg/kg IV and followed immediately by ketamine at 2.2-4.4 mg/kg IV. If desired, both diazepam and ketamine may be given mixed in the same syringe. Duration of anesthesia is brief, 5-15 minutes, and muscle relaxation may not be sufficient to allow laryngoscopy and orotracheal intubation when the lower dose is used. Guaifenesin (5%) used alone at 1.5-2.0 ml/kg IV provides little, if any, analgesia, and local anesthesia must be used when painful procedures are performed. Techniques that combine guaifenesin with ketamine (1 mg/ml) or a thiobarbiturate (2 mg/ml) provide better muscle relaxation during intubation. Transient apnea can occur with all techniques. For convenience, guaifenesin- based mixtures may be injected to effect with large (60 - 140 ml) syringes rather than administered by infusion. Most llamas can be intubated with approximately 67% of the calculated dose. Alpacas often require amounts approaching the calculated dose.

Propofol is a nonbarbiturate, nonsteroidal hypnotic agent that provides brief periods (5-10 minutes) of anesthesia in other species. As in other species sedation of the camelid prior to induction or use of a co-induction agent (diazepam, midazolam) will decrease the amount of propofol required. Induction and recovery are smooth. If injected rapidly, apnea may occur. Slow administration will usually prevent that complication. Anesthesia can be induced with propofol given at 2 mg/kg IV to unsedated llamas for restraint. Tracheal intubation is often difficult or not possible when propofol given at this dose in unsedated camelids and additional propofol (2-4 mg/kg) is usually needed to allow intubation. A light plane of anesthesia can be maintained with a constant infusion of propofol at 0.4 mg/kg/min with minimal cardiovascular effects in unsedated camelids. Mean time from discontinuation of infusion to sternal recumbency was 13 minutes and to standing was 22 minutes. Administration of propofol can be made more convenient and precise with use of infusion pumps. Except during special circumstances (for example, during MR imaging), economic considerations will dictate its use for maintenance of anesthesia in camelids.

Tiletamine-zolazepam, 2.2 mg/kg IV, provided 15-20 minutes of restraint and 25-35 minutes of recumbency. Depth of anesthesia was adequate to intubate the animals nasally but muscle relaxation was poor and oral laryngoscopy and intubation can be difficult. Camelids usually recover well from tiletamine-zolazepam.

Alfaxalone is a neuroactive steroidal anesthetic agent that has been available in the United Kingdom for a number of years for use in dogs and cats. It was licensed for use in Canada in Spring 2011 and was released in the United States during summer-fall 2014. It is primarily used as an induction agent. Given to unsedated alpacas at 2 mg/kg IV, it provides sufficient depth of anesthesia to allow tracheal intubation. Duration of anesthesia is approximately 10 minutes. Recovery to standing was approximately 35 minutes. Recovery was characterized as poor with some degree of excitement. It is likely recovery from this drug will be improved if it is used in sedated camelids or if anesthesia is maintained with an inhalant. As with propofol, economic considerations will dictate its use for anesthesia of camelids.

10 Mixtures of xylazine, ketamine, and guaifenesin have been used extensively to induce and maintain anesthesia in horses and domestic ruminants when an anesthesia machine was unavailable. These same drugs can be used to prolong anesthesia in llamas following induction with one of the other techniques. Final concentrations are 0.02% xylazine (0.2 mg/ml), 0.2% ketamine (2.0 mg/ml), and 5% guaifenesin (50 mg/ml). The calculated infusion rate is 1.2-2.4 ml/kg/hr although final administration rate may vary with patient temperament and invasiveness of the procedure. When using commercial administration sets (15 drops/ml), administration rate can be calculated with the following formula: (body weight) x (dose) x 15 drops/ml = drops/min 60 min/hr

The infusion rate of a 5% guaifenesin - 0.2 ketamine - 0.02% xylazine solution for a 150 kg llama would be:

(150 kg) x (2 ml/kg/hr) x 15 drops/ml = 75 drops/min 60 min/hr

Administration is made more convenient with use of a DripAssist® device from Shift Labs. This device attaches to the drip chamber of an administration set, counts the drops, and displays the information as either drops/min or ml/hr. Recovery to standing usually occurs within 30 minutes following discontinuation of infusion. Administration of xylazine-ketamine-guaifenesin can be made more convenient and precise with use of infusion pumps.

INTUBATION

After induction, tracheal intubation is recommended because it provides a secure airway and prevents aspiration of salivary secretions and gastric fluids if regurgitation occurs. Oral intubation (cuffed, 6-14 mm i.d.) is performed similar to domestic ruminants (Table 4). The camelid can be positioned either in lateral or sternal recumbency depending on personal preference. Conventional small animal or human endotracheal tubes are of sufficient length for crias, juvenile camelids, and some adult alpacas, endotracheal tubes 50 cm in length are used for larger alpacas and adult llamas. Oral blind intubation is usually unsuccessful and laryngoscopy with a 250-350 mm laryngoscope is recommended. The mouth can be held open with gauze loops or an equine mouth speculum. Even though the speculum must be held in place against the dental pad, the speculum opens the mouth more widely and provides better visualization of the oral pharynx than that obtained by other technics. Additionally because the mouth of herbivores does not open widely, the laryngoscope blade must be placed on the epiglottis to obtain adequate visualization of the larynx. Visibility of the larynx is improved by hyperextending the head and neck to make the orotracheal axis approach or exceed 180E and using gauze on a sponge forceps to swab the pharynx if secretions hinder visibility of the larynx. If desired, an obturator, e.g. a male canine urinary catheter, could be inserted through the endotracheal tube. The obturator should extend 6-10 cm beyond the bevel of the

11 Body Weight (kg) Endotracheal Tube Size (mm id) Oral Nasal

25 8 7 35 8 - 10 8 55 10 - 12 9 - 10 100 12 10 > 180 14 10 - 12

Table 4. Sizes of endotracheal tubes needed for camelids of various bodyweight. endotracheal tube and can be easily visualized as it is passed into the larynx. The endotracheal tube is then threaded off of the obturator into the trachea. Attempting intubation when anesthetic depth is insufficient will often provoke active regurgitation when the laryngoscope blade contacts the epiglottis or when the endotracheal tube contacts the larynx. With adequate depth of anesthesia, this reflex is eliminated. Desensitization of the larynx with topical lidocaine as is performed in sheep, goats, and swine is usually not necessary in camelids. However, desensitization of the larynx is helpful when intubation is difficult.

Nasotracheal intubation is also possible although it requires an endotracheal tube one size smaller (Table 4). Camelids are prone to epistaxis and use of lubricating compounds that contain phenylephrine is recommended. Blind nasal intubation is technically easier than oral intubation but nasal intubation under laryngoscopic control is technically more difficult than orotracheal intubation. Even though nasotracheal intubation can be more difficult, it offers the option of recovering the animal with the endotracheal tube in place as a method of preventing airway obstruction during recovery. With the same technic that is used in the horse, the endotracheal tube is advanced through the external nares into the ventral meatus with slow gentle pressure. Rotating the tube while passing it will increase the incidence of epistaxis. If an obstruction is encountered at approximately 6-10 cm in adult llamas it is usually due to placement of the tube in the middle meatus. If an obstruction is encountered more caudally, approximately 25 cm in adult llamas, the tube is likely in the pharyngeal diverticulum (Engel's diverticulum). In either case the tube should be withdrawn and redirected. If the endotracheal tube cannot be redirected past the pharyngeal diverticulum, placement of a prebent stylet (e.g. a piece of the smallest aluminum rod (3/16") available for Thomas splints) into the tube to direct the endotracheal tube tip ventrally is usually effective. The pharyngeal diverticulum is not as prominent in alpacas.

After the endotracheal tube has been advanced into the nasopharynx, the endotracheal tube can be rotated without increased risk of injury to the camelid. The camelid's head and neck should be hyperextended and the tube manipulated into the larynx. If the tube will not enter the larynx, placing a prebent stylet in the endotracheal tube to direct the tube tip ventrally into the larynx instead of the

12 esophagus is helpful. Although visibility of the larynx is somewhat limited, oral laryngoscopy will aid intubation and confirm correct and incorrect placement of the tube during intubation.

Endotracheal intubation can be confirmed with any of several techniques. Initially they include visualization of the endotracheal tube passing into the larynx and absence of stertorous breathing sounds. When transparent endotracheal tubes are used, water vapor condensation will appear and clear during each breath. One can feel gas being expelled from the tube during exhalation. If a suction bulb is evacuated and connected to the endotracheal tube, it will re-expand if the tube is in the trachea and will remain collapsed if the tube is in the esophagus, providing immediate confirmation of correct or incorrect placement of the tube. When the endotracheal tube is connected to the anesthesia machine, observation of synchrony between movement of the rebreathing bag and the thorax will be noted. Finally, if a capnograph or respiratory gas analyzer is available, presence of CO2 will be noted in exhaled gas.

MONITORING

As with any species, good anesthetic protocols require good monitoring techniques to tailor drug administration to the animal's requirements. Techniques employed to monitor depth of anesthesia in camelids are similar to those used for the traditional veterinary species. When animals are anesthetized and maintained with injectable techniques, instruments to help monitor anesthetic depth typically are not available and emphasis should be placed on variables than can be monitored with one’s senses. It is recommended that one consider use of a handheld pulse oximeter to help assess heart rate and rhythm and oxygenation. Several products are available. Instruments that utilize Masimo technology are preferred. Handheld pulse oximeter/capnography instruments are also available at additional expense. The addition of capnography allows one to assess respiratory rate and adequacy of ventilation.

Variables used to monitor response to intravenous anesthesia are: heart rate and rhythm, respiratory rate, mucous membrane color, perfusion time, pulse pressure, blood pressure, ocular reflexes, and arterial blood and respiratory gas analysis. Normal values (Table 5) for these variables are: heart rate, 60-90 beats/minute (adults, after atropine), 100-125 beats/minute (juveniles, after atropine), 28- 40 beats/minute (adults; after xylazine without atropine); pink mucous membranes and 1-2 second perfusion time. The mucous membranes of some camelids are pigmented, making assessment difficult. Pulse strength is assessed by palpation of caudal auricular, saphenous, and digital arteries. Pulse pressure should be full and bounding and will decrease as anesthetic depth increases. Normal values for respiratory rate are 10-25 breaths/minute (adults) and 15-30 breaths/minute (juveniles). Compared to horses and domestic ruminants, camelids tend to ventilate well as judged by blood gas analysis and respiratory gas analysis when anesthetized with halothane and if xylazine is not part of the anesthetic protocol.

Ocular reflexes are beneficial in assessing anesthetic depth. Usually the palpebral reflex of the dorsal eyelid remains present during surgical anesthesia. If the animal can move its ventral eyelid

13 Variable Normal Value

Cardiovascular System Heart Rate Adults (following atropine) 60 - 90 beats/minute Adults (following xylazine) 28 - 40 beats/minute Juveniles (following atropine) 100 - 125 beats/minute

Perfusion Time 1 - 2 seconds

Hemoglobin Saturation > 95%

Respiratory System Respiratory Rate Adults 10 - 25 breaths/minute Juveniles 15 - 30 breaths/minute

End tidal CO2 40 - 50 mmHg

Table 5. Normal physiological values for anesthetized camelids. without tactile stimulation, anesthetic depth is decreasing and eventually movement is likely. Nystagmus usually does not occur with decreasing depth of anesthesia. The corneal reflex should be present, but often is not assessed because of the reliability of the other reflexes and the risk of injury to the eye.

SUPPORTIVE THERAPY

Supportive therapy is an important part of anesthetic practice especially when the patient is compromised or debilitated. Supportive therapy is similar to that provided to the traditional veterinary species and includes patient positioning, fluid administration, cardiovascular support, mechanical ventilation, prevention of hypothermia in small camelids, intubation, and oxygen administration.

Although camelids do not appear to be prone to postanesthetic myopathy-neuropathy as is the horse, attention should be given to patient positioning and prevention of hypotension during anesthesia. Whether in dorsal or lateral recumbency, the camelid should be placed on a flat padded surface. To avoid myopathy or radial neuropathy when in lateral recumbency, the camelid’s dependent forelimb should be drawn forward so the thorax rests on the triceps rather than the humerus. Camelids have prominent eyes and special attention should be given to the dependent eye to avoid injury. The head should be positioned so oral secretions will drain from the mouth and not contact the eye. The head of non-intubated camelids should be positioned to facilitate drainage of secretions from the oral cavity.

14 Intravenous fluids are recommended but often not administered during intravenous anesthesia. Unless contraindicated, a polyionic, isotonic alkalinizing fluid (e.g. lactated Ringers or Normosol- R,® 5-10 ml/kg/hr) is preferred. Care should be taken to avoid administering excess fluid volume and often administration rate is decreased to 5 ml/kg after the first hour of anesthesia. Normal saline or sodium bicarbonate should be administered when indicated.

Efforts should be taken to keep the camelid warm during anesthesia performed during periods of cold ambient temperature as hypothermia can slow metabolism of the drugs and delay recovery. Use of blankets or other methods to help the camelid to conserve heat are recommended until the animal recovers. Use of forced air warmers (Bair Huggers®) can be considered and is advantageous.

Oxygen supplementation is recommended to camelids during intravenous anesthesia. Small diameter tubing can be inserted into the endotracheal tube of intubated camelids and connected to an oxygen source. Tubing diameter must be small enough to not impede exhalation. Oxygen can be insufflated nasally in non-intubated camelids by inserting small diameter tubing in the nares or nasopharynx. Typical flow rates are 3-7 lpm depending on camelid size and presence of an endotracheal tube.

RECOVERY

Camelids are obligate nasal breathers. If the animal was intubated during the procedure, gas exchange must be confirmed following extubation as airway obstruction can commonly occur during the transition from oral endotracheal tube breathing to nasal breathing. When anesthetizing horses or cattle one commonly removes the endotracheal tube as soon as the swallowing reflex returns. After doing so in camelids the animal tends to relax as soon as the stimulus of the endotracheal tube is removed and becomes prone to airway obstruction severe enough to cause death without intervention. Consequently, orotracheally intubated camelids should remain intubated until they are able to swallow, chew, cough, and are actively trying to expel the endotracheal tube to insure that the animal will be able to protect its airway following extubation. Precautions should be taken to prevent the camelid from damaging or aspirating the endotracheal tube. Even following these precautions occasional camelids will still experience airway obstruction following extubation. Because these animals are starting to regain consciousness, they are difficult to reintubate orally and may need to be re-anesthetized and re-intubated or may require emergency placement of a tracheotomy tube. The endotracheal tube of nasally intubated camelids can be removed after they stand. Airway obstruction is unlikely to occur in these animals because the animal has recovered much more completely from anesthesia and therefore, is more able to manage its airway. If regurgitation has occurred, the endotracheal tube should be withdrawn with the cuff inflated until the cuff reaches the larynx. Any ingesta that may have lodged in the pharynx or buccal cavity must be removed. It is preferable to have the camelid assume sternal recumbency as soon as possible. Although camelids recover well from general anesthesia with minimal assistance, an attendant should be available. Prolonged recovery (up to 2 hours) following halothane may occur subsequent to lengthy surgery or in animals that are stressed or compromised. Examples are fracture repair or

15 laparotomy. Nasotracheal intubation makes these patients easier to manage during recovery than orotracheal intubation. Use of isoflurane will shorten recovery as will use of sevoflurane or desflurane.

In conclusion, anesthetic management of South American camelids is similar to anesthetic management of domestic ruminants of similar size. When emphasis is placed on drug selection, airway management, and supportive care, anesthesia in these species to allow completion of surgical and diagnostic procedures can be very rewarding.

16 READING LIST

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