Clinical Question:

• Does dexmedetomidine lead to better short-term and long-term outcomes than propofol in mechanically ventilated adults with sepsis?

Methods:

• Multicenter (13 US hospitals), double-blinded, 422 mechanically ventilated patients with sepsis
• Notable exclusion criteria: pregnant, 2nd- or 3rd-degree heart block or persistent bradycardia requiring intervention, indication for bzds, expected to have NMB > 48 hrs, already had received mechanical ventilation >96 hrs
• Pain was treated with opioid pushes or fentanyl gtt
• Primary end point: number of calendar days alive without delirium or coma during the 14-day intervention period
  • Secondary efficacy end points included ventilator-free days at 28 days, death at 90 days, and global cognition at 6 months

Results:

• No sig difference in adjusted number of days alive without delirium or coma over the 14-day intervention period  (dexmedetomidine: 10.7 days vs. propofol: 10.8 days; OR, 0.96; 95% CI, 0.74 to 1.26; P = 0.79
  • No sig differences in the number of ventilator-free days at 28 days, in death at 90 days, or global cognitiion at 6 months
• Other notable findings:
  • Fewer patients in the dexmedetomidine group had ARDS or signs of trial drug withdrawal
  • Fewer patients in the propofol group extubated themselves
  • Open-label propofol received by 13% in the dexmedetomidine group and 8% in the propofol group) and dexmedetomidine (4% in the dexmedetomidine group and 3% in the propofol group)
  • Rescue midazolam was used in about half the patients, most often for procedural sedation or during NMB, 42% received antipsychotics
  • Similar proportions of patients had organ dysfunction, hypotension, or severe lactic acidosis
  • Symptomatic bradycardia requiring discontinuation of the trial drug was similar in the two groups

Take-home points:

• Dexmedetomidine or propofol are reasonable options for septic patients requiring mechanical ventilation without notable differences in delirium or mortality

References

Hughes CG, Mailloux PT, Devlin JW, et al. Dexmedetomidine or propofol for sedation in mechanically ventilated adults with sepsis. N Engl J Med. Published online February 2, 2021:NEJMoa2024922.