MENDS2 Trial

What was the research question?

Does the use of dexmedetomidine (intervention) improve days alive without delirium or coma (outcome) in mechanically ventilated adults with sepsis (population) compared to propofol (comparator)?

How did they do it?

A multicenter, double-blind, randomized, controlled trial randomized 432 septic patients on mechanical ventilation in 13 centers in the United States with 1:1 randomization looking at:

• Days alive without delirium or coma during the 14 days of intervention (primary)

• Number of ventilator-free days at 28 days (secondary)

• Mortality rate at 90 days (secondary)

• Age-adjusted total score on the Telephone Interview for Cognitive Status (TICS-T) questionnaire (secondary)

What did they find?

No siginficant difference in primary or secondary outcome measures:

• Median days alive without delirium (10.7 vs. 10.8).

• Ventilator-free days ( 23.7 vs. 24.0).

• Death at 90 days (38% vs. 39%).

• TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4).

• Similar safety profile between the two groups.

Any limitations?

• Some cross-contamination of sedative use

• Unmasking rate of 14%.

• Median of 22 hours to start trial medication after meeting inclusion criteria.

• Sample size was adjusted but still adequate power.

• Some exclusions were secondary to some physicians having preference on sedation choice.

What does it mean?

No change in practice, still both propofol and dexmedetomidine have an equipoise position in terms of sedation of septic patients on mechanical ventilation.