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In a prospective experimental crossover study, six clinically healthy donkeys were injected epidurally with normal saline (5 mL/animal), dexmedetomidine (5 μg kg−1), and xylazine (200 μg kg−1). Perineal analgesia, sedation, and degree of ataxia were evaluated preadministration and at 5, 10, 15, 30, 60, 90, 120, 150, and 180 minutes post-administrarion. Heart rate, respiratory rate, and rectal temperature were measured at the same time points. Epidural dexmedetomidine and xylazine produced complete bilateral perinea analgesia in all donkeys. The onset of analgesia was significantly rapid in dexmedetomidine-treated donkeys in comparison with xylazine (5.8 ± 2.04 vs. 14.2 ± 2.04 minutes, P = .004). Dexmedetomidine induced longer duration of perinea analgesia when compared with xylazine (160.0 ± 25.0 vs. 115.8 ± 14.97 minutes, P = .021). Both drugs induced moderate sedation (score 2). The sedative effect of dexmedetomidine was longer than that of xylazine (105 ± 10 vs. 80.83 ± 12 minutes, P = .017). All donkeys showed mild ataxia (score 1) after epidural xylazine and dexmedetomidine. Tail flaccidity was noticed in all donkeys at 15 and remained until 125 and 165 minutes postadministration of xylazine and dexmedetomidine, respectively. In conclusion, epidural dexmedetomidine induced faster and longer perinea analgesia with minimal cardiovascular effects than xylazine.Comparative, sedative, and analgesic effects of epidural dexmedetomidine and xylazine in donkeys were conducted.Six donkeys were used in a crossover study.Analgesia, sedation, ataxia, tail flaccidity as well as respiratory and heart rates were evaluated.Dexmedetomidine induced rapid onset longer duration of perinea analgesia than xylazine.Dexmedetomidine has longer sedative effect than that of xylazine.