Light sedation with dexmedetomidine does not lead to more days alive without acute brain dysfunction compared with propofol in mechanically ventilated adults with sepsis, according to the results of a multicenter, double-blind, controlled trial (MENDS2 Study; ClinicalTrials.gov Identifier: NCT01739933) published in The New England Journal of Medicine.
Current guidelines recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation; however, these sedatives have differences in arousability, immunity, and inflammation. It is unknown whether they affect outcomes in mechanically ventilated adults with sepsis undergoing light sedation.
Therefore, researchers randomly assigned 422 mechanically ventilated adults with sepsis to receive dexmedetomidine (214 received a median dose of 0.27 μg per kilogram per hour) or propofol (208 received a median dose of 10.21 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale (RASS; on which scores range from -5 [unresponsive] to [+4 combative]).
The median duration of receipt of the trial drugs was 3.0 days, and the median RASS score was =2.0. There was no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs 10.8 days), ventilator-free days (adjusted median, 23.7 vs 24.0 days), death at 90 days (38% vs 39%), or Telephone Interview for Cognitive Status questionnaire (TICS-T) score at 6 months (adjusted median score, 40.9 vs 41.4). In addition, safety end points were similar between the 2 groups.
“Our trial showed that among critically ill adults with sepsis who were receiving mechanical ventilation and for whom recommended light-sedation approaches were used, dexmedetomidine did not lead to better outcomes than propofol with respect to days alive without acute brain dysfunction, ventilator-free days, death at 90 days, or cognition at 6 months,” the study authors concluded.
Hughes CG, Mailloux PT, Devlin JW, et al; for the MENDS2 Study Investigators. Dexmedetomidine or propofol for sedation in mechanically ventilated adults with sepsis. N Engl J Med. Published online February 2, 2021. doi:10.1056/NEJMoa2024922