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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.