Dexmedetomidine, Propofol give similar outcomes in septic ventilated patients: MENDS2 trial
USA: The administration of dexmedetomidine or propofol yields similar outcomes in mechanically ventilated adults with sepsis being treated with light sedation, according to findings from the MENDS2 trial. The findings of the study were presented at the 2021 virtual Clinical Congress of the Society of Critical Care Medicine and simultaneously published in The New England Journal of Medicine.
Current guidelines recommend targeting light sedation with propofol or dexmedetomidine for adults receiving mechanical ventilation. There are differences between these sedatives in inflammation, immunity, and arousability. However, it is still not known of they have differential outcomes in mechanically ventilated adults with sepsis undergoing light sedation.
Against the above background, Christopher G. Hughes, professor of anesthesiology at Vanderbilt University Medical Center, in Nashville, Tenn., and colleagues set up the ENDS2 (Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients with Acute Respiratory Failure) trial -- a multicenter, double-blind trial.
Mechanically ventilated adults with sepsis were randomly assigned to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 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 primary end point was days alive without delirium or coma during the 14-day intervention period.
Of 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses — 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute.
The median duration of receipt of the trial drugs was 3.0 days, and the median RASS score was −2.0.
Key findings of the study include:
- 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; odds ratio, 0.96), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98), death at 90 days (38% vs. 39%; hazard ratio, 1.06), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94).
- Safety end points were similar in the two groups.
"Our findings show that among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol," wrote the authors.
The study titled, "Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis," is published in the New England of Medicine.