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Introduction: Weaning of mechanical ventilation while maintaining appropriate pain control and preventing delirium is one of the most challenging aspects of burn care. Dexmedetomidine, an α 2 -adrenergic receptor agonist used for sedation may improve intensive care unit (ICU) patients' arousal status and enhance patient comfort., Objectives: To determine the efficacy of dexmedetomidine vs. standardized usual care (midazolam or propofol) in maintaining sedation and reducing delirium in burn patients while weaning off mechanical ventilation., Material and Methods: A total of 56 mechanically ventilated patients who fulfilled the criteria for weaning were enrolled in the study. Group 1 (26 patients) received dexmedetomidine 1 mcg/kg over 15 minutes as a loading dose, followed by 0.4-0.1 mcg/kg/h. Group 2 (30 patients) received usual sedation with midazolam 0.08 mg/kg/h or propofol 15- 30 mcg /kg/min)., Results:  Dexmedetomidine was not associated with a significantly shorter duration of mechanical ventilation (Mean {IQR}: 9.3 {4,12} versus 7.5 {4,10}, p=0.3). Patients who received dexmedetomidine had a lower delirium rate (38,4% on Day 1 to 7,7% on Day 5) in comparison with patients from the usual care group (53,3% on Day 1 to 20% on Day 5) during the five days after the onset of weaning process (p=0.02) and had less need for supplemental use of analgesia (23.1% versus 53.3%, p=0.045) and antipsychotic agents (15.4% versus 53.3%, p=0.01). The most notable adverse effect of dexmedetomidine was bradycardia., Conclusions: Dexmedetomidine may provide effective light sedation and is associated with fewer sedation-related adverse effects in burn patients. Sedation with dexmedetomidine during the weaning process in adult burn patients was associated with lower delirium rates, a trend towards the earlier withdrawal of mechanical ventilation but did not seem to improve the total duration of mechanical ventilation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Stangaciu et al.)