Chiara E. Hampton1 and Thomas W. Riebold2 1 Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee, USA 2 Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA As in other species, sedation and anesthesia are often required for surgical or diagnostic procedures in ruminants. Most procedures in ruminants can be done during standing sedation with the aid of physical restraint tools and locoregional anesthesia to avoid potential complications from general anesthesia. The decision to induce general anesthesia may be influenced by a ruminant’s temperament, its specific anatomic and physiologic characteristics, and the type of procedure to be performed. Diagnostic and surgical procedures that are more complex require general anesthesia. In addition to discussing techniques for cattle, goats, and sheep, anesthetic techniques for South American camelids, primarily llamas and alpacas, are discussed. South American camelids do not accept restraint as well as domestic ruminants and often require sedation before local or regional anesthesia. Although 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 and the fact that alpacas can require approximately 10% greater doses of sedatives, anesthetic management of alpacas and llamas is similar. Considerations for preanesthetic preparation include preanesthetic physical examination, estimation of body weight, assessment of hematologic and blood chemistry values, fasting, venous catheterization, and the need for patient stabilization. During preanesthetic physical examination, subjects should be visually examined first and then restrained properly for the “hands‐on” portion of the physical examination to ensure the safety of personnel. Occasionally, depending on the patient’s temperament and demeanor, a complete physical examination is not possible. The components of the preanesthetic physical examination are similar to those of other domestic species. The chest should be auscultated for evaluation of heart rate and rhythm, as well as for respiratory rate and the character of respiratory sounds. This is particularly important in camelids where a wide variety of congenital cardiac abnormalities have been reported [1], as well as in small ruminants, which often present with subclinical pulmonary disease of bacterial, viral, or fungal origin. Synchronicity of peripheral pulses can be evaluated via palpation of the femoral pulse in camelids, small ruminants, and calves. In large cattle, the coccygeal or facial arteries can be used for this purpose [2]. Conjunctival or buccal mucous membranes can be evaluated for color and moisture level. Capillary refill time should take approximately 2 s. The FAMACHA© scoring system can be used in goats and sheep to detect the presence and the severity of anemia [3]. The frequency of ruminal contractions is an important vital sign to evaluate as ruminal atony may be present in cases of lactic acidosis and endotoxemia. A summary of normal findings of species‐specific scoring systems and vital signs is provided in Table 64.1. For accurate drug administration, body weight must be estimated or determined by weighing the animal. It is easy to overestimate the body weight of camelids because they are fairly tall, and their long haircoat obscures their body condition. Adult male llamas usually weigh 140–175 kg, occasionally reaching or exceeding 200 kg. Adult female llamas usually weigh 100–150 kg but may occasionally exceed 200 kg. Adult male alpacas usually weigh 60–100 kg, and adult female alpacas usually weigh 50–80 kg. The body weight of crias and small ruminants may be determined on a bathroom scale. Hematologic and blood chemistry values should be evaluated before anesthesia when possible, and the results should be compared with instrument‐specific reference values [8–11]. The Heska Element POC blood gas and electrolyte analyzer shows good performance with camelid blood and can be useful in the clinical setting, although complete agreement with automated chemistry analyzers was not documented [12]. Domestic ruminants have a multicompartment stomach with a large rumen that does not empty completely. South American camelids have a stomach divided into three compartments [13]. Each species, therefore, is susceptible to complications associated with recumbency and anesthesia with arterial hypoxemia, tympany, regurgitation, and aspiration pneumonia due to accidental aspiration of ruminal contents being the most common. To reduce risks associated with these potential complications, older calves, sheep, goats, and camelids should be fasted for 12–18 h and deprived of water for 8–12 h prior to anesthesia. Juvenile calves should be fasted and water withheld for no longer than 6–12 h. Fasting of neonates is not advisable because the rumen remains underdeveloped and hypoglycemia may result. Adult cattle are commonly fasted for 18–24 h and deprived of water for 12–18 h prior to general anesthesia, but definitive evidence‐based guidelines are currently lacking. Evidence in preslaughtered steers showed that decreasing the fasting time from 23–29 h to 2–6 h prevented hemoconcentration and dehydration associated with decreased water consumption during the fasting period and resulted in an overall improvement in animal welfare [14]. Furthermore, a 36‐h fast resulted in subclinical acute ruminal acidosis [15]. Fasting and water deprivation may decrease the likelihood of tympany by decreasing the volume of fermentable ingesta compared to non‐fasted cattle, reduce the incidence of hypoxemia [16], and preserve better pulmonary functional residual capacity [17]. However, regurgitation seems more common with prolonged fasting [16,18]. In cattle, fasting for 48 h is associated with bradycardia [19], which seems to persist for at least 48 h after resumption of food intake [20]. Due to the hormonal and metabolic changes associated with mobilization of energy substrates after prolonged fasting (> 24 h) in cattle [21], and the adverse events observed with 48‐h fasting, further studies to elucidate optimal fasting times in ruminants are warranted and needed. Until evidence‐based practices are built, practitioners are advised to observe fasting times that take into consideration and balance the advantages and disadvantages of short and prolonged fasting times. Although gas does not appear to accumulate in the first compartment of anesthetized camelids, these precautions may decrease the incidence of regurgitation in these species. In non‐elective cases, fasting for the suggested times is often not possible, and precautions should be taken to avoid aspiration of gastric fluid and ingesta. Even with these precautions, some ruminants will become tympanitic, and others will regurgitate. Table 64.1 Summary of normal physical examination findings in domestic ruminants and camelids. Data compiled from: a Kaplan et al. [4]; b Constable et al. [2]; c Ghosh et al. [5]; d Phythian et al. [6]; e Wildman et al. [7]. Venipuncture and catheterization of the jugular vein are often performed prior to anesthesia. Adult cattle require 12–14 gauge catheters for catheterization of the jugular vein. If difficulties in accessing the jugular vein are present, an auricular catheter (16–20 gauge) can be placed for administration of sedatives or induction agents in cattle restrained in a chute. Similar sized catheters are appropriate for adult camelids, calves, and large goats and sheep, and 18 gauge catheters are appropriate for juvenile camelids, sheep, and goats. South American camelids possess anatomical features that make jugular catheterization technically challenging. A detailed description of the venipuncture and catheterization techniques is provided elsewhere [22–24]. Physical restraint during venipuncture or catheterization varies and can consist of a handler holding the animal’s halter or use of head gates and chutes for adult cattle and llamas. If a camelid is fractious, performing ear twitching by squeezing the base of the ear may be helpful [25]. Turning the animal’s head excessively to either side may hinder venipuncture and catheter placement in goats and camelids, and may increase the likelihood of carotid arterial puncture in camelids. Infiltration of a small amount of local anesthetic such as lidocaine at the site of catheterization is recommended. Camelids lack a jugular groove, and their jugular vein lies deep to the sternomandibularis and brachiocephalicus muscles, ventral to cervical vertebral transverse processes and superficial to the carotid artery and vagosympathetic trunk within the carotid sheath for most of its length [22–24]. 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 bifurcation 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 or at any point caudal to it. Because of the close proximity of the carotid artery to the jugular vein, one must confirm that the vein has been catheterized and not the artery. After occlusion of the vessel, one will often be unable to see the jugular vein distend; however, the vein can be palpated particularly rostrally and more easily in females and castrated males because their skin is thinner. On occasion, one will be able to see the jugular vein distend on crias and juvenile camelids. Camelids can have four to five jugular venous valves that prevent flow of venous blood into the head when the head is lowered during grazing [23]. Contact with jugular venous valves may prevent catheterization; a site caudal to the point where the valve was contacted should be used. Finally, repeated unsuccessful attempts to place a jugular venous catheter have been associated with collapse and death. If a camelid begins to mouth‐breathe during catheterization, it is highly recommended to discontinue the procedure and allow the animal time to recover from the stress before proceeding. Stabilization of the patient should be performed prior to the anesthetic episode according to the animal’s health status. The extent of enophthalmos (recession of the globe), along with capillary refill time, mucous membrane color, packed cell volume, and plasma total solids can be used to estimate the patient’s fluid deficit [26]. Anecdotally, a reduction in the volume of the hump can be seen during dehydration in Brahman cattle, which regains volume with replacement of fluid deficits. Calculations for fluid replacement should include the existing deficit, metabolic water consumption, and ongoing losses. Attempts should be made to replace this volume, as well as fluids lost during the anesthetic episode through salivation and regurgitation. Anemia is not uncommon in small ruminants and South American camelids and should be addressed and treated as appropriate before surgical intervention. Ruminants do not necessarily require sedation prior to induction of anesthesia as other species do, mostly due to their temperament. While atraumatic physical restraint may be used in lieu of sedatives in some circumstances, sedation may be indicated in certain animals (primarily fractious adult cattle) to facilitate safe handling during the induction period. Sedation has been shown to decrease stress and increase the quality of collected semen of goats during electroejaculation [27]. This, along with the associated anesthetic‐sparing effects documented in several species, makes sedative administration beneficial, even in tractable animals. Because ruminants seldom experience emergence delirium, sedation during the recovery period is rarely required, in contrast to horses where this is common practice. In addition to the reduction in anesthetic requirements, preanesthetic sedation in ruminants may tend to lengthen the recovery period from general anesthesia [28] and increase the likelihood of regurgitation [29]. Drugs used to tranquilize and/or sedate ruminants include phenothiazines and butyrophenones, α2‐adrenergic receptor agonists (xylazine, detomidine, romifidine, medetomidine, and dexmedetomidine), dissociative agents (ketamine and tiletamine), pentobarbital, chloral hydrate, benzodiazepines (diazepam, midazolam, and zolazepam), and opioids (butorphanol, nalbuphine, hydromorphone, and morphine). Most of these drugs, when given alone or in combination at doses sufficient to induce recumbency, have been shown to cause arterial hypoxemia. Therefore, oxygen supplementation is highly recommended throughout the sedation/immobilization period if this practice is tolerated by the animal. Anticholinergics are usually not administered to domestic ruminants as premedication agents. Their antisialagogue properties are inconsistent in these species unless used in very high doses and frequently repeated. Anticholinergics, while decreasing the volume of secretions, may make them more viscous and more difficult to clear from the trachea. In the authors’ experience, camelids are prone to increased vagal discharge during intubation or with painful stimuli during surgery. Consequently, administration of atropine (0.02 mg/kg IV or 0.04 mg/kg IM) is recommended to prevent bradyarrhythmia in these species [30]. Alternatively, glycopyrrolate (0.005–0.01 mg/kg IM or 0.002–0.005 mg/kg IV) may be substituted for atropine [31,32]. Acepromazine is a phenothiazine devoid of analgesic properties. It is not commonly used in ruminants but can be used in a manner similar to its use in horses, although lower doses are required for cattle (0.01–0.03 mg/kg IM) compared to horses. The usual doses of acepromazine in sheep and goats are 0.03–0.05 mg/kg IV and 0.05–0.1 mg/kg IM, which may increase the risk of regurgitation during anesthesia [29]. Tranquilizing effects may last for up to 8 h, although usually do not exceed 4 h. The combination of acepromazine (0.05 mg/kg IV) with methadone (0.5 mg/kg IV), morphine (0.5 mg/kg IV), or tramadol (5 mg/kg IV) failed to improve the level of sedation observed with acepromazine alone in sheep [33]. In llamas, acepromazine (0.05 mg/kg IM) with or without butorphanol (0.1 mg/kg IM) did not produce sedative effects, but prolonged antinociception produced by tiletamine–zolazepam [34]. Acepromazine should not be injected into the coccygeal vein. The close proximity of the coccygeal artery makes the risk of inadvertent intra‐arterial injection possible, with the potential loss of the tail [personal communication: John C. Thurmon, 1970]. Acepromazine can also cause priapism and is not recommended for sedation in mature bulls with reproductive value. Prolapse of the penis during recovery increases the risk of injury to that organ as the animal stands. Acepromazine (0.035 mg/kg IV) is preferred over xylazine for endoscopic evaluation of the upper airways and laryngeal function in cattle if the procedure cannot be carried out without sedation [35]. Uterine blood flow and oxygen delivery to the fetus is preserved by acepromazine in cows during late gestation, in contrast to xylazine, which may critically impair delivery of oxygen to the fetus [36]. Finally, acepromazine is best avoided in newborn or neonatal patients, as well as in systemically ill and/or hypovolemic patients due to its hypotensive effects and depression of thermoregulation [37]. Azaperone is a butyrophenone that has been successfully used in combination with opioids (e.g., butorphanol and etorphine) and an α2‐adrenergic receptor agonist (e.g., xylazine and medetomidine) to sedate and immobilize several captive and wild ruminant species [28,38,39]. Its best use is in neuroleptoanalgesic combinations administered via the IM route. Xylazine, detomidine, romifidine, medetomidine, and dexmedetomidine cause sedation by stimulating central α2‐adrenergic receptors. The degree of sedation or chemical restraint produced by α2‐adrenergic receptor agonists depends on the dose administered and the animal’s temperament and species. These drugs act synergistically with opioids in producing sedation and analgesia. In cattle, the α2D‐adrenergic receptor subunit was considered predominant, which would partly explain the increased sensitivity of cattle to the sedative effects of these agents [40]. However, contrasting evidence found no difference in α2A/D‐adrenergic receptor subunit expression in bovine brain compared to pigs and rats [41]. Instead, this study found that the slope of the inhibition binding curve when G‐protein coupling was diminished was considerably lower in cattle for xylazine compared to detomidine, and this difference was not identified in swine or rats [41]. This species difference at the G‐protein level or further downstream in the receptor cascade may explain the higher sensitivity of cattle to xylazine compared to detomidine. In goats, activation of the α2D‐adrenergic receptor subunit produces better analgesia compared to the α2B‐ and α2C‐adrenergic receptor subunits, whereas the α2C‐adrenergic receptor subunit seems to be involved in thermoregulation [42]. Xylazine is often used to sedate or, in higher doses, restrain ruminants by producing recumbency and light planes of general anesthesia. As previously mentioned, there appears to be significant interspecies and intraspecies variation in the biological response to this drug. Overall, xylazine is much more potent in ruminants than it is in horses [43]. Among ruminants, goats appear to be more sensitive to xylazine than sheep [29,32,44], and cattle appear to be intermediate in sensitivity when compared to sheep and goats. South American camelids appear to be less sensitive than cattle but more sensitive than horses to the effects of xylazine; and among camelids, alpacas appear to be less sensitive to xylazine than are llamas. Hereford cattle are anecdotally reported to be more sensitive to xylazine than are Holstein cattle [45], and Brahmans are perhaps the most sensitive of all cattle breeds [46]. Extreme environmental conditions can cause cattle to have a pronounced and prolonged response to xylazine [47]. Low doses of xylazine (0.015–0.025 mg/kg IV or IM) typically provide sedation without recumbency in domestic ruminants [31,32,48]. Higher doses (0.1–0.2 mg/kg IV) provide sedation without recumbency in camelids [49]. Higher doses of xylazine will induce restraint with recumbency, heavy sedation, or possibly light planes of general anesthesia in domestic ruminants and camelids. Xylazine in goats (0.05 mg/kg IV or 0.1 mg/kg IM) [29,32,44], in sheep (0.1–0.2 mg/kg IV or 0.2–0.3 mg/kg IM) [29,32,44], and in cattle (0.1 mg/kg IV or 0.2 mg/kg IM) [46] will induce recumbency for approximately 1 h. Xylazine at 0.3–0.4 mg/kg IV usually induces 20–30 min of recumbency in llamas [23,24,30,50]. Alpacas have been reported to be less sensitive to xylazine compared to llamas and may require an approximately 10–20% increase in dose to achieve the same result [51]. In cattle undergoing claw treatments, xylazine (0.05 mg/kg IV) used alone has been shown to decrease hormonal and metabolic stress responses and potentiate the effects of local anesthetics, but worsened ventilation and oxygenation in laterally recumbent cows [52,53]. In 8‐day old calves, administration of xylazine (0.3 mg/kg IV) produced a similar degree of sedation compared to medetomidine (30 μg/kg IV), with a shorter duration of action. Cardiopulmonary effects included decreases in heart rate, cardiac index, and arterial oxygen tension (PaO2) when compared to baseline, and increases in central venous pressure, arterial carbon dioxide tension (PaCO2), and pulmonary arterial pressures. Interestingly, arterial blood pressures and vascular resistance increased with medetomidine but were decreased by xylazine [54]. The subcutaneous route is a viable and efficacious alternative to intramuscular administration of xylazine to neonatal Holstein calves, with similar onset and duration of action [55]. Variation in response to the analgesic effects of xylazine between breeds of sheep has been reported [56,57]. Mechanical and thermal thresholds for limb withdrawal are increased by administration of 0.05 mg/kg IV xylazine for a short amount of time (60 and 30 min, respectively) [58–60]. Xylazine causes hyperglycemia and hypoinsulinemia in cattle and sheep [61–66]. Ruminal tympany has been observed after administration of xylazine [67], likely induced by ruminal hypomotility [68]. Hypoxemia and hypercapnia are common side effects in domestic ruminants [29,45,69,70]. Dose‐dependent arterial hypoxemia and pulmonary edema can be seen in sheep after administration of all α2‐adrenergic receptor agonists [71,72]. In this species, activation of α2‐adrenergic receptors results in pathophysiologic changes including increase airway pressure [73,74], vasoconstriction and redistribution of pulmonary blood flow, and activation of pulmonary intravascular macrophages, which release a range of vasoactive mediators and cytokines [75]. In vitro contraction of tracheal smooth muscle [76] and in vivo smooth muscle contraction [73,74,77] have also been demonstrated, leading to bronchoconstriction. Histopathology of the lung reveals capillary rupture with endothelial damage, alveolar hemorrhage with damage to type I alveolar cells, and interstitial and alveolar edema [77,78]. These pathophysiologic consequences can be completely prevented in sheep by the administration of atipamezole, tolazoline, and idazoxan administered within 5–10 min of xylazine, but not with administration of yohimbine [76,79–81]. Not surprisingly, though, administration of tolazoline and idaxozan was also reported to shorten the duration of xylazine‐induced recumbency in this species [81]. Xylazine has an oxytocin‐like effect on the uterus of pregnant cattle [82] and sheep [83] and should be used with caution during late gestation as it may cause premature parturition and retention of fetal membranes [84]. In vitro exposure of isolated bovine uterine stripes to lidocaine after xylazine decreased the tonic effect induced by xylazine on bovine pregnant uteri [85]. Poorly trained or agitated male camelids tend to be less responsive, and debilitated individuals are more responsive to sedative doses of xylazine. Although complete data are not available on the cardiovascular and respiratory effects of xylazine in camelids, bradycardia [69] typically occurs as it does in other species [45,86–88]. Xylazine (0.2 and 0.4 mg/kg IM) has been shown to increase the duration of antinociception in llamas anesthetized with tiletamine–zolazepam [89]. Detomidine, like other α2‐adrenergic receptor agonists other than xylazine, is used less frequently in domestic ruminants. As in all species, detomidine is more potent than xylazine, but this difference in potency is less pronounced in ruminants compared to other species. Compared to xylazine, cattle appear to be less sensitive (more tolerant) to the sedating effects of detomidine and doses closer to those used in horses may be appropriate. Interestingly, detomidine may not have the same effect on the gravid uterus as xylazine does in cattle [90]. Detomidine can be given at 2.5–10 μg/kg IV in cattle [32,48,90,91] and at 10–20 μg/kg in sheep [29] to provide standing sedation for approximately 30–60 min. A high dose of detomidine (30 μg/kg IV) will produce recumbency in sheep. This dose is equivalent to xylazine at 0.15 mg/kg IV, medetomidine at 10 μg/kg IV, or romifidine at 50 μg/kg IV [71]. Sublingual detomidine (80 μg/kg) has been shown to produce adequate sedation in dairy calves prior to infiltration of lidocaine for disbudding [92]. In llamas, detomidine at doses as high as 40 μg/kg IV provides mild sedation but not chemical restraint [49]. In alpacas, the pharmacokinetic and sedative effects of detomidine gel administered intravaginally (200 μg/kg) were compared to intravenous administration of the injectable solution (70 μg/kg) [93]. Although bioavailability of intravaginal detomidine was only 20%, the degree of sedation (characterized as mild) and the duration of sedation were similar with both routes of administration [93]. The hyperglycemic effect of detomidine is greater than that produced by xylazine and medetomidine in sheep [94]. Romifidine has been used at 40, 80, and 120 μg/kg IV in Old World camels. Profound sedation and bradycardia of 4 h duration occurred with the highest dose [95]. Initial doses of 50–60 μg/kg IV are appropriate for South American camelids. As the stereoisomer of medetomidine, dexmedetomidine can be substituted for medetomidine at 50% of the medetomidine dose. Medetomidine given at 10 μg/kg IV induces recumbency in cattle [91]. Doses of 5 μg/kg IV in cattle [91] or 10 μg/kg IM in llamas [96] produce brief periods of standing sedation with minimal analgesia. When medetomidine is given at 30 μg/kg IV, it causes bradycardia, decreased PaO2, recumbency of 4 h duration, and sedation of 7 h duration in calves [54]. In non‐pregnant ewes, dexmedetomidine (5 μg/kg IV) and medetomidine (10 μg/kg IV) were equipotent when effects on isoflurane requirements and cardiopulmonary parameters were evaluated [72]. The addition of vatinoxan, a peripheral α2‐adrenergic receptor antagonist, to intramuscular medetomidine and ketamine for sedation in sheep ameliorated the negative cardiopulmonary effects produced by medetomidine and ketamine alone. The level of sedation produced and its subsequent reversal with atipamezole were not affected by concurrent administration of vatinoxan [97]. When given at 20–30 μg/kg IM to llamas, medetomidine provides profound sedation and recumbency lasting up to 120 min [96]. In alpacas anesthetized with IM tiletamine–zolazepam, the addition of dexmedetomidine dose‐dependently increased the duration of lack of motor response to claw clamping to a maximum of 40 min with a 20 μg/kg dose [98]. Transient hypoxemia was observed but judged to be clinically unimportant by the authors, but oxygen supplementation was recommended. In calves, dexmedetomidine (5 μg/kg IV) had a rapid onset of action (2.7 min) and produced a degree of sedation similar to xylazine (0.2 mg/kg IV) with a similar recovery time (80 min) [99]. Higher doses of all α2‐adrenergic receptor agonists can be expected to induce longer periods of recumbency in all species. Sedation following administration of α2‐adrenergic receptor agonists can be reversed by α2‐adrenergic receptor antagonists. These include atipamezole and yohimbine, which are specific to the α2‐adrenergic receptor, and tolazoline that has both α2‐ and α1‐adrenergic receptor antagonist activity. The dose of antagonist is dependent on the amount of agonist given and the interval between agonist and antagonist administration. The longer the interval between administration of the agonist and antagonist, the lower the dose of antagonist that is needed, as more metabolism of the agonist should have occurred. Giving the full dose of antagonist after significant metabolism of the agonist has occurred increases the likelihood that excitement will result, particularly if the antagonist is given IV. One could also consider giving the antagonist IM to make reversal more gradual. When yohimbine is given at 0.12 mg/kg IV, its efficacy varies in cattle [100,101]. Low doses of yohimbine are ineffective in sheep [81], but higher doses (1 mg/kg IV) will generally reverse xylazine sedation [102]. Yohimbine (0.12 mg/kg IV) has been used in llamas in combination with 4‐aminopyridine (0.3 mg/kg IV) to produce complete recovery from xylazine sedation [69]. Its use singly in camelids is also effective, and it can be administered at 0.12 mg/kg IV [49]. If sufficient arousal does not occur, additional yohimbine can be titrated to achieve the desired effect. Tolazoline is usually given at 0.5–2 mg/kg IV [100], but at the upper end of this dose range, it can cause hyperesthesia in unsedated cattle [103,104]. Following a 2 mg/kg IV dose, opisthotonus can occur in some animals; however, after excitement subsides, recovery is usually uneventful. A safety study on increasing doses of tolazoline (0.5, 1, 1.5, 2, 4, 8, and 10 mg/kg IV) was conducted in unsedated Holstein calves, with the highest dose producing “bright red conjunctival mucous membranes, coughing, nasal discharge, salivation, increased breathing effort, central nervous system depression, signs of abdominal pain, straining, head pressing, restlessness, increased frequency of defecation and diarrhea,” but no fatalities were reported [105]. Tolazoline can induce unwanted cardiovascular effects in calves such as transient bradycardia, sinus arrest, and hypotension [106]. Lower doses of tolazoline (0.5–1.5 mg/kg IV) have been recommended in ruminants and camelids, whereas others have suggested that the IV route should be avoided except in emergency situations [84]. Regardless, if tolazoline is to be given intravenously, it should be administered slowly to effect. Caution is advised when the recommended equine dose of tolazoline is administered to camelids, as severe complications including transitory apnea, cardiac arrest, seizure‐like activity, depression, and vague signs of abdominal pain have been observed, followed by death within 24 h. In a case report, serious complications ensued after administering a total dose of 6.4 mg/kg of tolazoline to a llama resulting in tachycardia, cardiac arrhythmias, hypotension, and gastrointestinal tract hypermotility [107]. One method of administering tolazoline to healthy camelids is to slowly give 50% of the calculated 1–2 mg/kg IV dose initially, and the remainder if reversal is inadequate [49]. In most instances, the initial dose (0.5–1 mg/kg IV) of tolazoline is adequate to provide sufficient arousal. Idazoxan can be given at doses of 0.05 mg/kg IV to sheep [81] and calves to reverse xylazine sedation [108]. Atipamezole at doses ranging from 20 to 60 μg/kg IV has been used to reverse medetomidine sedation in calves [32]. In sheep, atipamezole has been used at a total dose of 125 μg/kg, administered either entirely IV or 50% of the dose given IV and 50% given IM, to reverse sedation produced by 20–25 μg/kg of medetomidine [109,110]. In sheep administered intrathecal xylazine and detomidine, atipamezole reversed side effects but not analgesia based on the assessment of pain thresholds in response to an electrical stimulus [111]. Reduced feed consumption and ruminal contractions produced by medetomidine, romifidine, and detomidine in dwarf goats are completely antagonized by atipamezole [112]. Atipamezole given at 30 μg/kg IV will reverse xylazine sedation in camelids. Vatinoxan (formerly known as “MK‐467” and “L‐659,066”) is a peripheral α2‐adrenergic receptor antagonist which is devoid of central effects due to its inability to cross the blood–brain barrier. Currently, ruminant‐specific literature about vatinoxan is limited to the ovine species. The restriction of vatinoxan binding to peripheral α2‐adrenergic receptors means that it is able to ameliorate the negative cardiovascular effects accompanying administration of α2‐adrenergic receptor agonists without impacting central sedative effects. Vatinoxan’s peripheral selectivity has been confirmed in sheep, where cerebrospinal fluid and brain concentrations of the drug were minimal compared to those in plasma [113]. In sheep, administration of vatinoxan (0.75 mg/kg) prior to xylazine (0.5 mg/kg) improved PaO2 and SpO2 by preventing α2‐adrenergic receptor agonist‐induced effects on the ovine lung [114]. Prevention of dexmedetomidine‐induced bronchoconstriction, pulmonary edema, and arterial hypoxemia have been documented with vatinoxan (0.15 mg/kg IV) pretreatment in sheep anesthetized with sevoflurane [115]. Further investigation of the histopathologic changes seen with vatinoxan is needed as microscopic interstitial alveolar edema and hemorrhage were observed [114]. Doxapram, an analeptic agent, can be used to enhance the response to yohimbine or tolazoline. When administered at 1 mg/kg IV, doxapram was somewhat effective in cattle [116], but when administered at 2 mg/kg IV, it was ineffective in llamas [69]. For more information about doxapram, the reader is referred to Chapter 25. Diazepam, 0.25–0.5 mg/kg IV, injected slowly will provide 30 min of sedation without analgesia in sheep and goats [29,44]. This drug, at a dose of 0.2–0.5 mg/kg IV, has been shown to preserve normal rumen motility compared to xylazine, which reduced motility at 0.05 mg/kg, and caused complete atony at 0.125 mg/kg IV [117]. The pharmacokinetic profile of midazolam (0.5 mg/kg IM or IV) has been described in sheep [118] and alpacas [119]. Midazolam, 0.4–0.6 mg/kg IM [118,120,121] or 0.3–0.6 mg/kg IV [122,123], will provide sedation and recumbency in sheep and goats for 10–20 min with minor cardiorespiratory effects that are reversible with flumazenil (0.02 mg/kg IV). In alpacas, onset of sedation following 0.5 mg/kg midazolam is 0.4 min after IV administration and 15 min after IM administration [119]. Midazolam given at 1 mg/kg IM [120] or 0.6 mg/kg IV [122] can induce recumbency and profound sedation in goats. Increasing the dose to 1.2 mg/kg IV lengthens recumbency, lasting up to 30 min [121]. Midazolam given at 0.5 mg/kg IM to alpacas provides sedation without recumbency of approximately 100 min duration, whereas when given IV at the same dose, it provided sedation with recumbency for the same amount of time [124]. Butorphanol acts as a κ‐opioid receptor agonist and μ‐opioid receptor antagonist and provides sedation and mild analgesia in camelids and domestic ruminants. It is often given at doses of 0.05–0.5 mg/kg IM in sheep and goats [29,125,126] and 0.1–0.2 mg/kg IM in camelids [127], and produces analgesia for up to 2 h [128]. Ataxia and dysphoria have been reported following butorphanol administration (0.1–0.2 mg/kg IV) in sheep [126]. In the authors’ experience, camelids remain standing following butorphanol administration but may experience mild dysphoria. In isoflurane‐anesthetized alpacas, butorphanol (0.1 mg/kg IV) induces minimal cardiovascular changes, mainly via decreased systemic vascular resistance [129]. The addition of morphine (0.5 mg/kg IV), methadone (0.5 mg/kg IV), or tramadol (5 mg/kg IV) to xylazine (0.1 mg/kg IV) has been shown to induce similar cardiopulmonary changes to those of xylazine alone, but the quality of sedation was improved for up to 30 min after administration [130]. Nalbuphine (0.5 mg/kg IV) in combination with ketamine (5 mg/kg IV) in goats premedicated with xylazine (0.07 mg/kg IV) may produce adequate analgesia for left flank laparotomy [131]. The use of an earlier preparation of alfaxalone (Saffan®, a combination of alfaxalone and alfadolone solubilized in saline and Cremophor EL®) was investigated in ruminants in the late 1970s and early 1980s before the product was discontinued [132]. In 2015, alfaxalone was released in the United States in a different formulation (2‐hydroxypropyl‐β‐cyclodextrin), and over the last decade, it has been investigated in sheep, goats, and alpacas. Although the current cyclodextrin‐based formulation of alfaxalone is labeled for intravenous use in dogs and cats, it has been used successfully as a sedative when administered intramuscularly in several species [133–135]. The sedative properties of intramuscular alfaxalone in ruminants and camelids are yet to be investigated. A new formulation (40 mg/mL) of alfaxalone is been currently investigated in wild ruminants for remote immobilization [136] and may have future applications in domestic ruminants. Pentobarbital (2 mg/kg IV) has been used in cattle for standing sedation and tranquilization [137]. Caution must be exercised to avoid inducing excitement. Pentobarbital provides moderate sedation for 30 min and mild sedation for an additional 60 min. Chloral hydrate or chloral hydrate‐magnesium sulfate solutions can also be used to sedate ruminants [46]. Extravasation of these drugs will cause tissue necrosis, so they should be administered through a catheter confirmed to be placed within the vein. Combinations of xylazine and butorphanol have been used in domestic ruminants and camelids to produce neuroleptanalgesia. In domestic ruminants, doses are 0.01–0.02 mg/kg IV of each drug administered separately [personal communication: John C. Thurmon, 1993], and in camelids, 0.2 mg/kg IV of xylazine is administered with 0.02–0.04 mg/kg IV of butorphanol [personal communication: Michael J. Huber, 2013]. The duration of action is approximately 1 h. Combinations of midazolam (0.1 mg/kg IV) and butorphanol (0.1 mg/kg IV) given simultaneously provide restraint of short duration [138]. Combinations of butorphanol, ketamine, and xylazine have also been used to restrain camelids [138]. The combination is prepared by combining 10 mg (1 mL) of butorphanol, 1000 mg (10 mL) of ketamine, and 100 mg (1 mL) of xylazine. It is administered at 1 mL/18 kg IM to alpacas and at 1 mL/23 kg IM to llamas [138]. Recumbency occurs within 5 min and lasts approximately 25 min. Other combinations of xylazine, ketamine, and butorphanol (“Ketamine Stun”) have also been used in ruminants [48] and camelids [138]. Ruminant doses for the IV route of the Ketamine Stun are lower compared to IM, and onset of action for the IV route is shorter compared to the IM route. Typically, xylazine at 0.025–0.05 mg/kg, ketamine at 0.3–0.5 mg/kg, and butorphanol at 0.05–0.1 mg/kg are administered IV [48]. Animals will become recumbent for 15–25 min and administration of an additional partial dose of ketamine (50% of the original dose) will lengthen the duration of analgesia. If venous access is not feasible, the upper end of the doses cited above can also be administered IM or subcutaneously to achieve a longer but less intense form of chemical restraint. Alternatively, a combination of xylazine (0.05 mg/kg), butorphanol (0.025 mg/kg), and ketamine (0.1 mg/kg) can also be given IM to render ruminant patients more cooperative [48]. Onset occurs within 10 min, and duration of action is approximately 45 min with an additional 30 min needed to resume standing. In calves, 0.1 mg/kg of ketamine and 0.05 mg/kg of xylazine administered IV have been shown to be efficacious and safe when administered to aid with surgical castration [139]. Given IV, the combination of xylazine at 0.22–0.33 mg/kg, ketamine at 0.22–0.33 mg/kg, and butorphanol at 0.08–0.11 mg/kg induces more predictable restraint in camelids [138]. Animals will become recumbent and analgesia lasts for 15–20 min. Administration of an additional partial dose of ketamine will lengthen the duration of analgesia. When given IM to camelids, the dose range is increased to xylazine at 0.22–0.55 mg/kg, ketamine at 0.22–0.55 mg/kg, and butorphanol at 0.08–0.11 mg/kg [138]. Onset occurs within 10 min and duration of action is extended to approximately 45 min. General anesthesia can be induced by either injectable or inhalation techniques. Widely available drugs include ketamine, guaifenesin, tiletamine–zolazepam, propofol, alfaxalone, pentobarbital, isoflurane, and sevoflurane. If available, the thiobarbiturates and halothane could also be used. In small ruminants weighing less than 50–100 kg, anesthesia can be induced using isoflurane or sevoflurane delivered by face mask, or with an injectable technique. If desired, calves and sheep can be intubated nasally while awake or following sedation using a technique similar to that used in foals and then connected to the anesthesia circuit for induction [140]. In larger ruminants, anesthesia is commonly induced using an IV technique but, if the animal’s temperament dictates it, the IM route is also possible. In small or debilitated camelids, or in camelids restrained with xylazine–ketamine, tiletamine–zolazepam, or other injectable combinations, anesthesia can be induced with isoflurane or sevoflurane by face mask. Mask induction in healthy untranquilized adult camelids is usually not attempted because application of the mask may provoke spitting. The addition of nitrous oxide (50% of total flow) to the inspired gas mixture will speed induction; however, administration of nitrous oxide to ruminants and camelids beyond induction may cause distension of gas‐containing organs, resulting in tympany. When available, the thiobarbiturates thiopental and thiamylal were used extensively in veterinary anesthesia, both alone and in combination with guaifenesin. Used alone, they quickly induce anesthesia. Muscle relaxation is relatively poor but still sufficient to accomplish intubation. The acid–base status and physical status of patients affect the actions of these drugs. Acidemia increases the non‐ionized fraction (i.e., the active portion) of the drug, increasing its activity and thus decreasing the dose required [141]. Because patients in shock are often acidemic, altered pharmacokinetics and hemodynamics may cause a relative overdose. In addition, the heart, brain, and other vital organs receive a larger portion of cardiac output when patients are in shock [142]. Recovery from induction doses of thiobarbiturates is based on redistribution of the drug from the brain to other tissues in the body. Metabolism of the agent continues for some time following recovery until final elimination occurs. Maintenance of anesthesia with thiobarbiturates is not recommended because saturation of tissue depots causes recovery to become dependent on metabolism resulting in prolongation. Concurrent use of non‐steroidal anti‐inflammatory drugs (NSAIDs) may delay recovery as thiobarbiturate is displaced from protein [143]. Drug interactions appear to be minimal in most instances. Thiopental can be given at 6–10 mg/kg IV to unsedated animals and will provide approximately 10–15 min of anesthesia. Camelids often require additional thiopental for tracheal intubation [30]. Thiamylal is administered in a similar fashion although in slightly lower doses, usually 25–30% less. Pentobarbital has been used to anesthetize domestic ruminants but is no longer commonly used. If a situation arises in which it is used, the dose is 20–25 mg/kg IV, half given rapidly and the remainder to effect. When given at an anesthetic dose, pentobarbital causes profound respiratory depression and is not an effective analgesic. Sheep appear to metabolize pentobarbital more quickly than other species [29]. Recovery in domestic ruminants is usually prolonged, and other anesthetic techniques are more appropriate. Ketamine is a very versatile drug that has been used in many species. It is an N‐methyl‐D‐aspartate (NMDA) receptor antagonist and acts by disrupting the signal pathway between the thalamus and the cortex, causing a dissociated state. It causes cardiovascular stimulation due to sympathetic discharge and can cause dysphoria, hallucinations, and excitement, in addition to tonic‐clonic muscle activity when used alone in horses. Those same traits characterize its use in ruminants, although perhaps not to the same extent. Ketamine in single and repeated IV doses has been shown to increase plasma cortisol in calves premedicated with xylazine [144]. Although ketamine, when used as a sole agent, does not eliminate the swallowing reflex, tracheal intubation can be accomplished in most ruminants. However, co‐administration of a sedative (e.g., benzodiazepines, α2‐adrenergic receptor agonists, and/or guaifenesin) to improve muscle relaxation is recommended, but may abolish the swallowing reflex. Ketamine will induce immobilization and incomplete analgesia when given alone, but it is usually combined with a sedative or tranquilizer. Most commonly, xylazine or a benzodiazepine is recommended. Xylazine at 0.1–0.2 mg/kg IM can be given first, followed by ketamine at 10–15 mg/kg IM in small domestic ruminants [29,44,145]. In goats, it is preferable to use the lower dose of xylazine followed by ketamine [29,44]. Anesthesia usually lasts about 45 min and can be prolonged by injection of 3–5 mg/kg IM or 1–2 mg/kg IV of ketamine. The longer duration of action of xylazine obviates the need for its readministration in most cases. Alternatively, xylazine at 0.03–0.05 mg/kg IV followed by ketamine at 3–5 mg/kg IV, or xylazine at 0.1 mg/kg IM in goats or 0.2 mg/kg IM in sheep, followed by ketamine at 3–5 mg/kg IV, can provide anesthesia lasting 15–20 min [29]. Adult cattle can by anesthetized with xylazine at 0.1–0.2 mg/kg IV followed by ketamine at 2 mg/kg IV [146]. The lower dose of xylazine is used when cattle weigh more than 600 kg [146]. Anesthesia lasts approximately 30 min but can be prolonged for 15 min with additional ketamine at 0.75–1.25 mg/kg IV [146]. When evaluated in sheep, xylazine at 0.1 mg/kg IV and ketamine at 7.5 mg/kg IV provided anesthesia lasting 25 min and caused a decrease in cardiac output, mean arterial pressure, and peripheral vascular resistance [147]. Medetomidine has been combined with ketamine to induce anesthesia in calves. Because medetomidine (20 μg/kg IV) is much more potent than xylazine, lower doses of ketamine (0.5 mg/kg IV) can be used [148]. However, a local anesthetic at the surgical site may be required when ketamine is used at this dose [148]. Anesthesia can be reversed completely with α2‐adrenergic receptor antagonists without excitement occurring during recovery. Using lidocaine (2 mg/kg IV) in conjunction with ketamine (2.5 mg/kg IV) in calves premedicated with xylazine and butorphanol increases sedation but fails to decrease ketamine requirements for endotracheal intubation [149]. Diazepam (0.1 mg/kg IV) or midazolam (0.1 mg/kg IV) immediately followed by ketamine (4.5 mg/kg IV) can be used in domestic ruminants. Muscle relaxation is usually adequate for tracheal intubation, although the swallowing reflex may not be completely obtunded. Anesthesia usually lasts 10–15 min following benzodiazepine–ketamine administration, with recumbency of up to 30 min. Higher doses of diazepam (0.25–0.5 mg/kg IV) with ketamine (4–7.5 mg/kg IV) have also been used in sheep and provide the same duration of anesthesia [29,44,147]. Investigations into the cardiopulmonary effects of diazepam (0.375 mg/kg IV) and ketamine (7.5 mg/kg IV) in sheep have shown a decrease in cardiac output and an increase in peripheral vascular resistance without affecting arterial pressure [147]. Midazolam can be substituted for diazepam in goats and given at 0.4 mg/kg IM followed by ketamine at 4 mg/kg IV after recumbency occurs (approximately 15 min). Anesthesia lasts approximately 15 min [120]. Xylazine (0.25–0.35 mg/kg IM) and ketamine (6–10 mg/kg IM) administered 15 min later usually provides 30–60 min of recumbency in camelids [23,30]. One disadvantage of this technique is that larger adult llamas require a relatively large injection volume. Simultaneous administration of xylazine (0.44 mg/kg IM) and ketamine (4 mg/kg IM) usually provides restraint for 15–20 min [50,150]. Higher doses of xylazine (0.8 mg/kg IM) and ketamine (8 mg/kg IM) given simultaneously usually induce sedation/anesthesia within 5 min that lasts 30 min [150]. Depth of anesthesia varies with the amount given and the camelid’s temperament but is usually sufficient for minor procedures such as suturing lacerations, draining abscesses, or applying casts. When any of these combinations provides insufficient anesthetic depth, supplemental local anesthesia may be required in order to complete the procedure. Tracheal intubation may not be possible. However, these combinations heavily sedate and immobilize the animals, facilitating venipuncture and administration of additional anesthetic agent or application of a face mask to increase the depth of anesthesia when necessary. If desired, xylazine (0.25 mg/kg IV) and ketamine (3–5 mg/kg IV) may be administered 5 min apart to obtain a more uniform response and sufficient depth of anesthesia for tracheal intubation in camelids [23]. Diazepam (0.1–0.2 mg/kg IV) or midazolam (0.1–0.2 mg/kg IV) and ketamine (4.5 mg/kg IV), as used for domestic ruminants, produces recumbency that lasts approximately 20 min and should provide enough muscle relaxation for tracheal intubation in camelids. Guaifenesin is a centrally acting skeletal muscle relaxant that exerts its effect at the internuncial neurons in the spinal cord and at polysynaptic nerve endings [151]. It can be used alone to induce recumbency in domestic ruminants and camelids but is not recommended because it imparts little, if any, analgesia [152]. The addition of ketamine, or historically a thiobarbiturate, to a guaifenesin solution improves induction quality and decreases the volume required for induction. Muscle relaxation is improved compared with induction with ketamine or thiobarbiturates given alone. Typically, 5% guaifenesin solutions are used as hemolysis can occur with 10% guaifenesin solutions in ruminants [153]. Commonly, these solutions are given rapidly to effect, either by gravity and a large gauge catheter or by pressurizing the bag or bottle, in either tranquilized or untranquilized patients. The volume of the calculated dose when using 5% guaifenesin solution is 2 mL/kg. The amount of ketamine added to guaifenesin varies but is commonly 1 g per 50 g of guaifenesin. The amount of thiobarbiturate added to guaifenesin varies but is commonly 2 g per 50 g of guaifenesin. For convenience, guaifenesin‐based mixtures may be injected with large (60–140 mL) syringes rather than administered by infusion to camelids and small ruminants to allow greater control over administration. If desired, xylazine can also be added to ketamine–guaifenesin solutions for induction and maintenance of anesthesia in cattle [146,154,155] and sheep [156]. Final concentrations are guaifenesin 50 mg/mL, ketamine 1–2 mg/mL, and xylazine 0.1 mg/mL. This solution is infused at 0.5 to 1 mL/kg IV for induction. For more information about guaifenesin, the reader is referred to Chapter 25. Tiletamine–zolazepam is a combination of equal parts of tiletamine and zolazepam available for use as an anesthetic agent in cats and dogs. When used alone, tiletamine induces poor muscle relaxation and causes excitement during recovery. The addition of zolazepam to tiletamine modifies these effects. As with ketamine, the swallowing reflex remains but may be obtunded. Like ketamine, this combination provides slight cardiovascular stimulation, causing the heart rate to increase [157]. Elimination of tiletamine and zolazepam is not uniform, with variation occurring in each drug’s clearance between species. Differential clearance of the two drugs can affect recovery quality [157]. In many respects, tiletamine–zolazepam can be considered to be similar to ketamine premixed with diazepam or midazolam. When used alone in horses, it provides unsatisfactory anesthesia [158]. Muscle relaxation is poor and recovery is characterized by excitement. However, when combined with a sedative such as xylazine, it can be used successfully in horses. Because of differences in temperament between horses and domestic ruminants and camelids, tiletamine–zolazepam can be used successfully with or without xylazine in these species. However, the addition of xylazine to tiletamine–zolazepam will lengthen the effect. Tiletamine–zolazepam given at 4 mg/kg IV in untranquilized calves caused minimal cardiovascular effects and provided anesthesia that lasted 45–60 min [159]. Xylazine (0.1 mg/kg IM) followed immediately by tiletamine–zolazepam at 4 mg/kg IM produced onset of anesthesia within 3 min, and anesthesia that lasted approximately 1 h [160]. Calves were able to stand approximately 130 min after injection. Increasing xylazine to 0.2 mg/kg IM increased the duration of anesthesia and recumbency and the incidence of apnea, necessitating intubation and ventilatory support [160]. Xylazine can also be administered at 0.05 mg/kg IV followed by tiletamine–zolazepam at 1 mg/kg IV [146]. Tiletamine–zolazepam given at 12 mg/kg IV in sheep provides approximately 2.5 h of surgical anesthesia, with a total recumbency time of 3.2 h [161]. More recent investigations in sheep have shown that tiletamine–zolazepam, given at 12–24 mg/kg IV, causes cardiopulmonary depression with anesthesia of approximately 40 min [162]. The addition of xylazine (0.11 mg/kg IV) to tiletamine–zolazepam (13.2 mg/kg IV), improved muscle relaxation and prolonged the duration of anesthesia and analgesia by 2.5 times [163]. Rather than using these relatively large doses, it is more appropriate to decrease the initial dose of tiletamine–zolazepam to 2–4 mg/kg IV and administer additional drug as required to prolong anesthesia. Butorphanol at 0.5 mg/kg IV combined with tiletamine–zolazepam at 12 mg/kg IV given either simultaneously or 10 min apart induces 25–50 min of anesthesia in sheep, with mild cardiopulmonary depression [164]. Tiletamine–zolazepam at 4 mg/kg IM can immobilize llamas for up to 2 h [165]. The length of recumbency is unaffected by administration of flumazenil, indicating that the duration of action is more likely influenced by tiletamine rather than zolazepam [165]. Cardiovascular function is preserved although hypercapnia and hypoxemia can occur in some animals. Airway reflexes are maintained. Local anesthesia may be required for some surgical procedures [165]. Tiletamine–zolazepam at 2 mg/kg IM can immobilize llamas for approximately 1 h [34] and can be combined with acepromazine, butorphanol, or xylazine which will lengthen the duration of immobilization [34,89]. Furthermore, the combination of both xylazine (0.15 mg/kg IM) and morphine (0.5 mg/kg IM) administered with tiletamine–zolazepam to llamas has been shown to produce antinociception for longer than when it is combined with either xylazine or morphine alone [166]. In camelids, tiletamine–zolazepam (2 mg/kg IV) can provide 15–20 min of anesthesia and 25–35 min of recumbency. Depth of anesthesia is adequate for nasal intubation, but muscle relaxation is poor and oral intubation is difficult.
64
Ruminants
Introduction
Preanesthetic preparation
Alpaca/Llama
Goat
Sheep
Cattle
Body condition score
5
(range 1–9)a
2.5–4
(range 0–5)c
3
(range 0–5)d
3
(range 1–5)e
Heart rate (beats/min)
60–90a
70–90b
70–90b
60–80b
Respiratory rate (breaths/min)
10–30a
25–35b
10–20b
10–30b
Rectal temperature (°F)
99.5–102a
103.0b
102.0b
101.5b
Ruminal contractions (F/min)
3–5a
1b
1b
1b
Sedation/chemical restraint
Anticholinergics
Acepromazine and azaperone
α 2 ‐Adrenergic receptor agonists
Xylazine
Detomidine
Romifidine
Medetomidine and dexmedetomidine
α 2 ‐Adrenergic receptor antagonists
Yohimbine
Tolazoline
Idazoxan
Atipamezole
Vatinoxan
Doxapram
Benzodiazepines
Opioids
Alfaxalone
Other sedatives
Common combinations for chemical restraint
Induction
Barbiturates/thiobarbiturates
Ketamine
Guaifenesin
Tiletamine–zolazepam
Propofol
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