Commonly Used Preanesthetics


2
Commonly Used Preanesthetics


HuiChu Lin


Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, AL, USA


Preanesthetic tranquilization or sedation is rarely necessary in ruminants, but on occasion its use may be required to calm intractable animals for the safety of the animals and also for the safety of the personnel handling the animals. The choice of whether a tranquilizer/sedative is needed for a particular animal is based on that animal’s temperament and physical condition. However, a complete physical examination prior to anesthesia in large ruminants often is not feasible because some of these animals are not accustomed to being handled and restrained, particularly free‐ranging animals. In addition to relocation to unfamiliar surroundings for the intended procedure, special equipment like a head catch or restraining chute that may be used for proper restraint of an intractable animal can add another level of stress to the patient. In large aggressive animals, the use of a tranquilizer/sedative will minimize the stress from forceful restraint, ease the anesthetic induction process, and decrease the dose of general anesthetic required, thus preventing the possibility of disastrous hypotension due to the use of large doses of an anesthetic. Camelids and swine are less tolerant of physical restraint; consequently, deep sedation or general anesthesia is often needed to perform even minor surgical procedures. Oral administration of a tranquilizer/sedative may be used to reduce stress associated with physical restraint in free‐ranging animals under field conditions or for animals intolerant of physical restraint. Drugs used for tranquilization and sedation are also used to produce chemical restraint. In ruminants and camelids, oral medication has to pass through the rumen or rumen‐like C1 compartment, respectively. Thus, the absorption and distribution of the drug will be affected by forestomach motility and the pH of the contained fluid [1]. Reticuloruminal motility is controlled by the medullary gastric center of the brain. Physical conditions affecting the patient, such as depression, pain, fear, excitement, and extreme distension of the ruminal wall (e.g. bloating), or administration of analgesics like opioids, α2 agonists, or anesthetics (e.g. thiopental and propofol) have been reported to decrease gastric motility resulting in prolonged gastric emptying time and increased absorption of a drug [1].


The difference in pH between saliva (8.2), plasma (7.4), and ruminal content (5.5–6.5) also affects the absorption and distribution of the drug by its effect on the degree of ionization of the drug. Nonionized drugs have higher lipid solubility and easily diffuse across cell membranes, whereas ionized drugs have lower lipid solubility and are therefore less capable of diffusion across cell membranes. Weak acidic drugs ionize and accumulate in the alkalinized saliva and thus allow the delivery of large quantities of the drug into the rumen with the flow of saliva. Once in the more acidic environment of the rumen, ionized drugs become nonionized and diffuse across the rumen membrane into the local blood circulation. On the contrary, drugs that are weak bases become ionized and accumulate in the rumen. The degree of ionization and the diffusion of the drug between saliva, ruminal content, and plasma is constantly changing, which increases the difficulty in predicting the bioavailability, distribution, and calming effect of an orally administered tranquilizer/sedative [1]. Drugs administered intramuscularly or intravenously usually produce more predictable and reliable calming effects in ruminants and camelids, and are the preferred routes for administering a tranquilizer/sedative when possible. For monogastric animals like pigs, the pH in the stomach is acidic (1.5–2.5) [2], therefore orally administered acidic drugs will present with a greater percentage in nonionized form and thus better and faster absorption from the stomach and greater bioavailability of the drug. Basic drugs tend to have lower bioavailability due to a higher degree of ionization of the drugs in the stomach.


2.1 Acepromazine (Phenothiazine Derivatives)


2.1.1 Cattle


Acepromazine produces mild tranquilization without analgesia in animal species. It produces a calming effect by blocking dopaminergic receptors at the basal ganglia in the brain [3]. The drug has minimal effects on heart rate and respiratory function. Direct depression on myocardial contractility and a decrease in cardiac output with subsequent hypotension often observed with the administration of acepromazine are the result of its effect on blocking α1 adrenoceptors located at the myocardium [4, 5]. In addition to a calming effect, acepromazine produces beneficial effects such as antiarrhythmic and antiemetic effects. Acepromazine may cause relaxation of the esophagus and cardia, which increases the risk of regurgitation in ruminants [6, 7]. Thus, special measures to protect the airway should be taken if the animal is to be placed in lateral or dorsal recumbency during the procedure. Use of the coccygeal vein for intravenous (IV) injection should be avoided when administering acepromazine because of its close proximity to the coccygeal artery [3]. Prolapse of the penis with potential subsequent trauma following the administration of acepromazine as reported in horses may occur in ruminants as well. The IV and intramuscular (IM) doses of acepromazine recommended for ruminants are 0.01–0.02 and 0.03–0.1 mg/kg, respectively [8]. The duration of tranquilization of acepromazine is usually 2–4 hours when administered at recommended dosages, but effects of 4–8 hours have been reported [9]. The use of acepromazine is contraindicated in debilitated or hypovolemic animals due to its hypotensive effect [3]. In addition, acepromazine depresses the thermoregulatory center, resulting in significant hypothermia and prolonged recovery in anesthetized newborns and neonatal animals. Acepromazine (0.03 mg/kg IM) has been administered occasionally to calm fractious bulls prior to induction of anesthesia with IV xylazine and ketamine.


2.1.2 Small Ruminants and Camelids


Acepromazine, though rarely used in small ruminants, can be administered at 0.05–0.1 mg/kg to produce mild tranquilization [10]. The drug has been used as an alternative for xylazine in goats with urethral obstruction where increased urine output associated with α2 agonists is contraindicated. Doses from 0.05 to 0.2 mg/kg can be administered IM or IV to produce tranquilization in sheep and goats [11]. In camelids, 0.033 mg/kg has been used to produce some calming effect in a female guanaco for eye examination [12]. However, a dose of up to 0.15 mg/kg was needed to quiet an aggressive male llama prior to induction of anesthesia with halothane [13].


2.1.3 Swine


Acepromazine is not an effective tranquilizer in pigs, for though tranquilized, they can still resist and fight the imposing restraint viciously. The doses of acepromazine recommended for pigs are 0.11–0.44 mg/kg IV or IM with a maximum total dose of 15 mg [8]. Large doses of acepromazine have been administered in addition to local anesthesia to sows undergoing cesarean section surgery, resulting in severe hypotensive shock. Several sows did not recover following the surgery [14]. IM doses of 0.05–0.5 mg/kg have been given to Vietnamese potbellied pigs with an unreliable calming effect even with high doses [15]. Acepromazine is frequently used in combination with ketamine or Telazol (tiletamine/zolazepam) to produce excellent sedation and muscle relaxation [16]. In pigs susceptible to malignant hyperthermia, acepromazine at 1.1 and 1.65 mg/kg IM has been reported to reduce the incidence of malignant hyperthermia by 40% and 73%, respectively. A lower dose of 0.55 mg/kg IM only delayed but did not prevent the onset of the episode [17].


2.2 Droperidol and Azaperone (Butyrophenone Derivatives)


Butyrophenone derivatives like droperidol and azaperone have pharmacological effects very similar to acepromazine (phenothiazine derivatives). Droperidol alone has been administered to pigs at 0.3 mg/kg IM to produce sedation for 2 hours [18]. However, droperidol is seldom administered alone to animals; it is manufactured as a proprietary combination of droperidol (20 mg/ml) and fentanyl (0.4 mg/ml) and marketed as Innovar‐Vet for veterinary use. Innovar‐Vet is a neuroleptanalgesic combination which consists of a tranquilizer (droperidol) and an analgesic (fentanyl). The combination of two drugs not only potentiates the central nervous system (CNS)‐depressing effect and the analgesic effect of each drug but also reduces the dose requirement for each drug, which decreases the side effects of each drug. Innovar‐Vet is often used to calm intractable or vicious animals but is rarely used in ruminants. When given at 0.19, 0.25, or 0.3 ml/kg to sheep, Innovar‐Vet was reported to produce adequate analgesia and smooth induction and recovery [19]. Innovar‐Vet had been shown to produce satisfactory calming effect in pigs (1 ml/12–25 kg [26.4–55 lb] IM). However, pigs often sneezed and became more excited if stimulated while under the influence of Innovar‐Vet [20]. Variable responses ranging from light sedation to pronounced relaxation and analgesia have been reported when 1 ml/10 kg (22 lb) of Innovar‐Vet was administered to young pigs [21]. Better and more reliable sedation was observed when xylazine was administered with Innovar‐Vet [14]. When administered to miniature pigs, Innovar‐Vet induced CNS stimulation rather than sedation [22]. Contrary to the previous report, Piermattei and Swan [23] showed that 1 ml/14 kg (30.8 lb) of Innovar‐Vet IM produced good sedation prior to halothane anesthesia.


Azaperone, another butyrophenone derivative, has pharmacologic effects similar to acepromazine and droperidol. Hughes et al. [24] compared the effects of azaperone and acepromazine in free‐ranging sheep. At 1 mg/kg, azaperone produced a calming effect and reduced the stress response as evidenced by calmer behavior and a greater comfort level of the animals studied. In this study, azaperone appeared to be more effective in reducing the stress response than acepromazine [24]. Madsen et al. [25] observed greater disorientation for a longer duration with azaperone. Interestingly, sheep tended to disperse with acepromazine but they tended to congregate with azaperone.


In pigs, azaperone has been shown to be the most effective tranquilizer. Azaperone has been used for the prevention of aggressiveness and savaging of newborn pigs by sows, for the treatment of stress, and for the completion of minor surgical procedures. At 2.2 mg/kg IM, azaperone was effective in reducing fighting following intermingling [26]. Approximately 20 minutes of deep sedation sufficient for minor surgeries was produced by 4–8 mg/kg of azaperone IM. Excessive salivation during deep sedation has been observed [2631]. Practitioners should keep in mind that tranquilizers like acepromazine, droperidol, azaperone, diazepam, and midazolam do not possess analgesic effect. Therefore, a tranquilizer may render the animal unresponsive to painful manipulations, but the physiological stress response resulting from painful stimulations still exists. Similar to acepromazine, azaperone is effective in preventing malignant hyperthermia episodes due to halothane in susceptible pigs. Doses of 0.5–2.0 mg/kg IM azaperone offered 100% protection against malignant hyperthermia in susceptible Pietrain pigs [32].


2.3 Detomidine, Dexmedetomidine, Medetomidine, Romifidine, and Xylazine (α2 Agonists)


The α2 agonists (e.g. xylazine, detomidine, medetomidine, dexmedetomidine, and romifidine) are classified as sedatives/analgesics. In addition to effective sedation, these drugs produce profound analgesia and good central muscle relaxation. The α2 agonists produce their pharmacologic effects by their actions on both the central and peripheral α2 adrenoceptors. Stimulation of central (presynaptic) α2 adrenoceptors inhibits the release of catecholamines, thus reducing the response to excitatory input, and as a result sedation occurs. Peripheral (postsynaptic) α2 receptors are found in the vasculature, pancreatic islet cells, and uterine muscles. As a result, transient hypertension, hypoinsulinemia, hyperglycemia, and oxytocin‐like effect are often associated with the administration of an α2 agonist [33]. Other side effects associated with the administration of α2 agonists include direct myocardial depression and augmentation of parasympathetic stimulation resulting in a decrease in cardiac output, bradycardia, and hypotension. Up to a sixfold increase in urine output subsequent to a decrease in secretion of antidiuretic hormone is a common side effect of α2 agonists. The central muscle‐relaxing effect produced by α2 agonists is believed to be mediated through the inhibition of nerve impulse transmission at the internuncial neurons of the spinal cord, brain stem, and subcortical level of the brain [34]. Because of this, α2 agonists are often given in combination with anesthetics that do not provide adequate muscle relaxation for surgical procedures. For example, when ketamine is administered alone, it is often associated with muscle tremors, jerking activity, and rigidity; xylazine is administered concurrently to improve the muscle relaxation during ketamine anesthesia. All α2 agonists, though considered as pure α2 agonists, also have affinity for α1 receptors. The α2 : α1 selectivity ratios for xylazine, detomidine, romifidine, and medetomidine/dexmedetomidine are 160 : 1, 260 : 1, 340 : 1, and 1620 : 1, respectively [35, 36].


2.3.1 Cattle


2.3.1.1 Xylazine


Xylazine is the most popular sedative in large animal practice today. Cattle are much more sensitive to xylazine than horses and require only one‐tenth of the dose needed for horses to produce the same degree of sedation [33]. The degree of sensitivity to xylazine varies within breeds, and Brahmans appear to be the most sensitive, Herefords intermediate, and Holsteins are the least sensitive [37]. Xylazine produces potent sedation, profound analgesia, and good muscle relaxation. It is frequently used for chemical restraint or anesthetic adjunct in ruminants. Xylazine alone produces dose‐dependent CNS depression from standing sedation (0.015–0.025 mg/kg IV or IM) [21, 38] to recumbency and immobilization (0.1 mg/kg IV or 0.2 mg/kg IM) [39]. Administration of xylazine to ruminants in the final trimester of pregnancy may cause premature parturition and retention of fetal membranes [40, 41]. In pregnant dairy cows during late gestation, administration of xylazine (0.04 mg/kg IV) resulted in a significant increase in uterine vascular resistance (118–156%) and a decrease in uterine blood flow (25–59%) accompanied by a drastic decrease in fetal O2 delivery (59%) [42]. Due to these detrimental effects on the fetus, the use of xylazine during late gestation in pregnant cows is not recommended. Fayed et al. [43] observed pronounced and prolonged drug effects when xylazine was administered to cattle under high ambient temperature. Xylazine should be used with extreme caution in animals with preexisting cardiopulmonary disease or urinary tract obstruction due to its adverse effects on the myocardium and urine output [33]. Higher dose of xylazine (single average dose, 0.55 ± 0.18 mg/kg) delivered by tranquilizer gun has been used to produce complete immobilization to capture free‐ranging cattle [44]. Xylazine is often used with butorphanol to produce neuroleptanalgesia. Enhanced sedation and analgesia develop when these two drugs are administered concurrently. Administration of high doses of butorphanol alone to nonpainful cattle may induce slight CNS stimulation and behavioral changes. Thus, when used in combination with xylazine, it is recommended the dose of butorphanol be maintained below 0.05 mg/kg to avoid butorphanol‐induced CNS excitation offsetting the sedative effect of xylazine [45]. Detailed discussion of chemical restraint techniques using xylazine combinations is described in Chapter 3.


Epidural administration of xylazine to standing cattle produced effective perineal analgesia for 2.5–4 hours. Compared to epidural lidocaine, xylazine produced less disruption of hind limb motor function and provides a longer duration of perineal analgesia [46, 47]. Systemic effects like mild to moderate sedation and slight ataxia sometimes occur following caudal epidural administration of xylazine, which is a result of absorption of the drug into blood circulation from the injection site and/or diffusion of the drug into cerebrospinal fluid (CSF) with subsequent cranial migration of the drug into the CNS. Similarly, studies in humans [48] and dogs [49] showed that diffusion of epidurally administered morphine into the CSF and the subsequent migration of the drug up the spinal cord, rather than the total injected drug volume, were the primary factors responsible for the widespread analgesia of epidural morphine. IV administration of an α2 antagonist such as tolazoline reversed the systemic effects (sedation and ataxia) but did not affect the caudal epidural analgesia of xylazine [50]. It is believed that the epidural analgesia of xylazine is the result of the binding of xylazine to the α2 adrenoceptors located in the dorsal horn of the spinal cord, not the effect of xylazine on the central α2 adrenoceptors in the CNS [51, 52]. Therefore, IV or IM administration of an α2 antagonist does not affect the binding of an α2 agonist to the receptors in the epidural space due to low concentration of the α2 antagonist in the epidural space.


2.3.1.2 Detomidine


Detomidine has pharmacologic effects that are very similar to those of xylazine. Interestingly, ruminants appear to be less sensitive to detomidine than they are to xylazine. The dose of detomidine required to produce standing sedation is similar to the dose required for horses. When administered at 0.05 mg/kg IV or IM to adult cattle, detomidine produced effective sedation, though the analgesic effect appeared to be more intense when the drug was administered intravenously [53]. Standing sedation of 30–60 minutes was evident with 0.025–0.01 mg/kg IV of detomidine [38, 54, 55]. Unlike xylazine, detomidine does not produce an oxytocin‐like effect on the uterus in gravid cattle at IV doses less than 0.04 mg/kg. However, doses greater than 0.04 mg/kg were observed to cause increased electrical activity of the uterine muscle without inducing synchronizing burst potentials characteristics of parturition [56, 57]. This indicates that detomidine is less likely to induce premature parturition in pregnant ruminants at recommended doses and this may make it safer for use in pregnant ruminants. Slight sedation without analgesic effect was observed when 0.01 mg/kg of IM detomidine was given to Lanka buffaloes. Moderate sedation with analgesia was observed at 0.02 mg/kg, while deep sedation with excellent analgesia occurred with 0.04 mg/kg. However, 50% of the animals receiving 0.04 mg/kg became recumbent. When increasing the dose to 0.08 mg/kg, detomidine induced recumbency and complete immobilization in these buffaloes. The author of the study concluded that 0.02 and 0.04 mg/kg of detomidine induced adequate sedation and analgesia that suffices most clinical and practical purposes [58]. At higher doses (0.08–0.1 mg/kg IM), detomidine induced complete immobilization and excellent muscle relaxation, but regurgitation and subsequent aspiration pneumonia could be a risk if the animal’s airway is not protected [58, 59]. In dairy cattle, IV detomidine alone (0.1 mg/kg) induced moderate sedation with significant decreased heart rate and respiratory rate for 39–55 minutes. Similar to xylazine and butorphanol administered to Holstein cows as mentioned previously, CNS excitation produced by butorphanol (0.05 mg/kg IV) seemed to offset the sedative effect of detomidine (0.1 mg/kg IV) when the two drugs were administered concurrently [45].


Caudal epidural administration of detomidine (0.04 mg/kg) induced perineal analgesia within 5 minutes following administration and lasted for 175 minutes [60]. In horses, caudal epidural detomidine has a slightly faster onset and shorter duration of perineal analgesia than xylazine, 12.5 ± 2.7 and 160 ± 8 minutes versus 13.1 ± 3.7 and greater than 165–180 minutes, respectively [61].


Recently, sublingual detomidine gel with a concentration of 7.6 mg/ml in a 3‐ml syringe is available for horses to be used in the field or on the farm. When administered sublingually to horses, the oral bioavailability was 22% and the peak plasma concentration was approximately 40% that of the plasma concentration following IM administration. A mild to moderate degree of sedation occurred within 30–40 minutes and lasted 90–180 minutes [62, 63]. Minor procedures like grooming or examination can be accomplished with this application [64]. The pharmacokinetic results from blood and urine samples in horses suggested a 48‐hour and 3‐day withdrawal time of detomidine should be sufficient [63, 65]. In calves undergoing disbudding, the efficacy of sublingual administration of detomidine (0.08 mg/kg) was compared to IV detomidine (0.03 mg/kg). The bioavailability of detomidine was 34% with time to maximum plasma concentration at 66.0 ± 36.9 minutes. Maximal sedation occurred at 40 minutes following sublingual application as compared to 10 minutes following IV administration. Heart rate decreased in both groups. All calves were adequately sedated and offered little resistance for injection of local anesthetic prior to disbudding [66].


When administered at 0.08 mg/kg IV or IM to six cows, the concentration of detomidine measured in milk was below 0.4 ng/g at 11 hours, and no detectable concentration was measured at 23 hours post administration. Drug residue was detected in the liver of three cows (0.3–3.9 μg/kg tissue weight) and in the lung (2.3 μg/kg), kidney (0.3 μg/kg), and muscle of the injection site (0.5 μg/kg) of one cow, respectively. Only minute concentrations of 0.4 and 2.5 ng/g in the lungs and 0.7 and 0.8 ng/g in the muscle sample from the injection site were detected in two cows at 48 hours post administration [67]. These residual concentrations of detomidine in different tissues would affect the withdrawal time in food‐producing animals.


2.3.1.3 Medetomidine


IV administration of medetomidine (0.005 mg/kg) to domestic ruminants produced a short duration of standing sedation with minimal analgesia [54]. However, IM administration of 0.03 mg/kg in domestic calves resulted in lateral recumbency with analgesia lasting for 60–75 minutes [68]. Higher doses of medetomidine (0.04 mg/kg in heifers, 0.08 mg/kg in cows) delivered by tranquilizer gun have been used successfully to produce immobilization for the capture of free‐ranging cattle. In both studies, atipamezole was used effectively to reverse medetomidine’s effect [69, 70]. In one study, two cows were in the last month of pregnancy and both calved normally at full term [70]. Caudal epidural injection of medetomidine (0.015 mg/kg) has been reported to induce rapid onset of perineal analgesia, similar to that of lidocaine, but with a significantly longer duration (4–9.5 hours). Moderate sedation and ataxia were observed in these cows. Two cows became recumbent at 20 and 40 minutes following drug administration, but both were easily coaxed to stand. It was believed that the recumbency in these two cows was caused by the nature of the ruminants during deep sedation and was not the result of motor nerve function disruption due to caudal epidural medetomidine [71].


2.3.1.4 Romifidine


When administered at 0.02 mg/kg IM to cattle, romifidine produced deep sedation with recumbency at 14.8 ± 3.4 minutes after injection. The duration of immobilization was 45.2 ± 3.4 minutes, and standing recovery occurred at 78.7 ± 17.7 minutes. The degree of analgesia produced by romifidine at this dose was similar to that produced by 0.2 mg/kg of IM xylazine. Similar to other α2 agonists, romifidine caused bradycardia, and the heart rate was significantly lower with romifidine. Other side effects of romifidine observed included bradypnea, decreased hematocrit, and ruminal tympany [72]. Romifidine (0.05 mg/kg) and morphine (0.1 mg/kg) have been combined and diluted in saline to a total volume of 30 ml and administered through a caudal epidural to Holstein–Friesian cows. Significant perineal analgesia with moderate sedation lasted 6 hours, but on occasion analgesia lasted up to 12 hours. Cows in this study tended to sit down and assume a recumbent position. The authors were not clear whether the recumbency was due to the deep sedation and ataxia from systemic absorption of romifidine and morphine into the blood circulation or the natural instinct of the cattle to sit down during sedation. One cow developed hind limb paresis and became recumbent 24 hours after drug administration. The cow showed no improvement 72 hours later and was humanely euthanized. Postmortem examination did not reveal any pathological changes like necrosis, inflammation, or degenerative lesions in the spinal cord to explain the hind limb paresis. However, the cow did have severe muscle necrosis of the adductor muscles, mild hepatic lipidosis, and moderate acute abomasal ulceration [73].


2.3.2 Small Ruminants and Camelids


2.3.2.1 Xylazine


Similar to cattle, small ruminants (e.g. sheep and goats) are very sensitive to xylazine, and goats are more sensitive than sheep [6]. Camelids (e.g. alpacas, llamas), though more sensitive to xylazine than horses, are not as sensitive as cattle and small ruminants. Therefore, the dose of xylazine required to produce a similar degree of sedation in goats is equal to or slightly less than that of cattle, whereas a slightly higher dose is required in camelids than in cattle and small ruminants. Compared to llamas, alpacas require dosages 10–15% higher than the recommended dose for llamas. Xylazine alone produces dose‐dependent CNS depression ranging from standing sedation to recumbency and immobilization in small ruminants and camelids. Extreme caution should be practiced when xylazine is used in animals with preexisting cardiopulmonary disease and urinary tract obstruction or in late pregnancy [33, 40, 74]. Severe hypoxemia and pulmonary edema have been implicated as the cause of death in sheep under xylazine sedation/anesthesia [7578]. Lateral recumbency in conscious sheep has been reported to induce a significant decrease in PaO2 [79]. Xylazine has been reported to cause hypoxemia in xylazine‐sedated standing sheep [80, 81]. Apparently, all α2 agonists cause similar and significant decrease in PaO2 in sheep without affecting the PaCO2 [82]. Nolan et al. (1986) [83] demonstrated that xylazine‐induced increased airway pressure (from 13.7 to 35 mmHg) in sheep was a result of dose‐dependent stimulation of peripheral (postsynaptic) α2 adrenoceptors located in the airway smooth muscles (0.002–0.02 mg/kg). The effect of xylazine on the airway smooth muscles occurred within 5 minutes following IV administration and lasted longer than 60 minutes, long after the measured cardiovascular variables had returned to baseline values [83]. Furthermore, severe pulmonary parenchymal damage was seen with substantial morphological changes, such as extensive damages to capillary endothelium and alveolar type I cells, intra‐alveolar hemorrhage, and interstitial and alveolar edema. Such changes occurred almost immediately following IV administration of 0.15 mg/kg of xylazine [84]. Bronchospasm and venospasm due to direct action of α2 adrenoceptors on the vascular and bronchial smooth muscles, transient α2‐induced platelet aggregation with pulmonary microembolism, and release of cytokines and other inflammatory mediators subsequent to α2‐induced pulmonary intravascular macrophage activation have been suggested as the contributing factors for the development of hypoxemia in sheep [85].


Caudal epidural administration of xylazine (0.07–0.1 mg/kg), with or without lidocaine, induced long‐lasting somatic analgesia for open castration in rams (8 hours, without lidocaine) and correction of vaginal prolapse in ewes (24 hours, with 0.5 mg/kg of lidocaine) [86, 87]. However, visceral analgesia induced by epidural xylazine alone may not be sufficient for ligation of the spermatic cord [86].


2.3.2.2 Detomidine


At 0.02 mg/kg IV, detomidine produced sedation which is comparable to that of 0.04 mg/kg of xylazine [88]. Increasing the dose to 0.03 mg/kg, detomidine induced recumbency in sheep with sedation that was equivalent to 0.15 mg/kg of xylazine and 0.01 mg/kg of medetomidine [89]. Effective sedation and significant but transient hypotension and bradycardia followed by tachycardia and hypoxemia were reported during sedation with 0.091 ± 0.004 mg/kg of IV detomidine. Cardiac arrhythmias (e.g. atrioventricular block, ST elevation, and premature ventricular contraction) were also observed in this study [90]. Deep sedation with hypotension of 108 ± 9.1 minutes occurred when detomidine (0.092 ± 0.006 mg/kg IV) was combined with diazepam (0.7 ± 0.2 mg/kg IV). Cardiac arrhythmias, but not hypoxemia or hypercapnia, were observed when diazepam was administered with detomidine [91]. Obviously, hypoxemia and pulmonary edema can occur with any of the α2 agonists, but the severity of hypoxemia was reported to be less with detomidine [85]. IV administration of α2 agonists normally induces a characteristic biphasic blood pressure response characterized by transient hypertension followed by longer‐lasting hypotension. The initial hypertension is the result of vasoconstriction from stimulation of peripheral (postsynaptic) α2 adrenoceptors, and the subsequent hypotension is due to activation of central (presynaptic) α2 adrenoceptors resulting in decreased sympathetic outflow and catecholamine release [33]. Celly et al. [82] reported a longer‐lasting hypertension was observed following IV administration of detomidine (0.03 mg/kg). Interestingly, in that study, mean arterial blood pressure showed the characteristic biphasic patterns for all four α2 agonists (xylazine, detomidine, medetomidine, and romifidine), but all the values were within or above normal values. In other words, hypotension, defined as below‐normal arterial blood pressure values, was not observed with any of the α2 agonists in this study [82]

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Nov 10, 2022 | Posted by in SUGERY, ORTHOPEDICS & ANESTHESIA | Comments Off on Commonly Used Preanesthetics

Full access? Get Clinical Tree

Get Clinical Tree app for offline access