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Objective: The aim of this study was to compare dexmedetomidine-butorphanol (DB) and midazolam-butorphanol (MB) combinations for sedation, and analgesia in burn patients undergoing dressing changes.Methods: A total of 56 ASA I–II burn patients were included in this single-center randomized clinical trial. The ages of these patients were between 20 and 60 years. TBSA ranged from 10% to 50%. They were randomized to group DB and group MB during dressing change. In the DB group, each patient received a bolus dose of dexmedetomidine (0.5 μg kg−1) and intermittent boluses of butorphanol (20 μg kg−1). In the MB group, each patient received a bolus dose of midazolam (0.05 mg kg−1) and intermittent boluses of butorphanol (20 μg kg−1). The primary outcomes were sedation scores and pain scores. The second outcomes were vital signs, side effects, and butorphanol consumption.Results: The sedation scores of these two groups did not differ significantly (p > 0.05), and the pain scores of these groups were not significantly different (p > 0.05). More patients had hypotension in the DB group than in the MB group (6 versus 0, p = 0.01), but the number of patients who had respiratory depression was higher in the MB group compared with the DB group (4 versus 0, p = 0.038). Butorphanol consumption in the MB group was higher than in the DB group (p = 0.025).Conclusion: Dexmedetomidine is comparable to midazolam when combined with butorphanol in burn patients during dressing change. Compared with midazolam, it has the advantage of opioid-sparing effect.Clinical Trial Registration: [http://www.chictr.org.cn/showproj.aspx&proj=130622], identifier [ChiCTR2100049325].

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