Inhaled Sedation in Acute Respiratory Distress Syndrome: The SESAR Randomized Clinical Trial.

Summary

Among 687 adults with moderate-to-severe ARDS, sevoflurane sedation resulted in fewer ventilator-free days through day 28 (median difference −2.1; 95% CI, −3.6 to −0.7) and lower 90-day survival (47.1% vs 55.7%; HR, 1.31; 95% CI, 1.05–1.62) compared with propofol. Sevoflurane also increased 7-day mortality (19.4% vs 13.5%; RR, 1.44) and reduced ICU-free days.

Key Findings

• Sevoflurane led to fewer ventilator-free days through day 28 (median difference −2.1; 95% CI, −3.6 to −0.7) versus propofol.
• Ninety-day survival was lower with sevoflurane (47.1% vs 55.7%; hazard ratio 1.31; 95% CI, 1.05–1.62).
• Sevoflurane increased 7-day mortality (19.4% vs 13.5%; relative risk 1.44; 95% CI, 1.02–2.03) and reduced ICU-free days.

Clinical Implications

Propofol should be preferred over sevoflurane for sedation in moderate-to-severe ARDS. Centers using volatile sedation should re-evaluate protocols and monitor outcomes closely.

Limitations

• Open-label to treating clinicians, which may influence co-interventions
• Inhaled sedation logistics and device availability may limit generalizability

Future Directions

Mechanistic analyses to understand why volatile sedation worsens outcomes, subgroup analyses (e.g., etiologies of ARDS), and trials of alternative sedation strategies.