MENDS2
Trial question
What is the role of dexmedetomidine in mechanically ventilated patients with sepsis?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
43.0% female
57.0% male
N = 422
422 patients (181 female, 241 male).
Inclusion criteria: mechanically ventilated adult patients with sepsis treated with recommended light sedation approaches.
Key exclusion criteria: severe cognitive impairment; pregnancy or lactation; second- or third-degree heart block or persistent bradycardia requiring intervention; allergy to dexmedetomidine or propofol; indication for benzodiazepines; moribund state; receipt of mechanical ventilation for > 96 hours.
Interventions
N=214 dexmedetomidine (at a dose of 0.2-1.5 mcg/kg/hr adjusted by bedside nurses to achieve target sedation goals set by clinicians).
N=208 propofol (at a dose of 5-50 mcg/kg/min adjusted by bedside nurses to achieve target sedation goals set by clinicians).
Primary outcome
Median days alive without delirium or coma at 14 days
10.7 days
10.8 days
10.8 days
8.1 days
5.4 days
2.7 days
0.0 days
Dexmedetomidine
Propofol
No significant
difference ↔
No significant difference in median days alive without delirium or coma at 14 days (10.7 days vs. 10.8 days; OR 0.96, 96% CI 0.74 to 1.26).
Secondary outcomes
No significant difference in median ventilator-free days at 28 days (23.7 days vs. 24 days; OR 0.98, 95% CI 0.63 to 1.51).
No significant difference in death at day 90 (38% vs. 39%; HR 1.06, 95% CI 0.74 to 1.52).
No significant difference in median Telephone Interview for Cognitive Status questionnaire score at 6 months (40.9 points vs. 41.4 points; OR 0.94, 95% CI 0.66 to 1.33).
Safety outcomes
No significant differences in organ dysfunction, hypotension, severe lactic acidosis.
Conclusion
In mechanically ventilated adult patients with sepsis treated with recommended light sedation approaches, dexmedetomidine was not superior to propofol with respect to median days alive without delirium or coma at 14 days.
Reference
Christopher G Hughes, Patrick T Mailloux, John W Devlin et al. Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis. N Engl J Med. 2021 Apr 15;384(15):1424-1436.
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