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

Summary

In this multicenter phase 3 RCT of 687 adults with moderate to severe ARDS, inhaled sevoflurane sedation resulted in fewer ventilator-free days at day 28 and lower 90-day survival compared with propofol. Early mortality (7-day) and ICU-free days were also worse with sevoflurane.

Key Findings

• Ventilator-free days at day 28 were lower with sevoflurane vs propofol (median difference -2.1 days; 95% CI -3.6 to -0.7).
• Ninety-day survival was lower with sevoflurane (47.1%) vs propofol (55.7%); HR 1.31 (95% CI 1.05–1.62).
• Sevoflurane increased 7-day mortality (19.4% vs 13.5%; RR 1.44) and reduced ICU-free days through day 28 (median difference -2.5 days).

Clinical Implications

For moderate to severe ARDS requiring deep sedation, prefer intravenous propofol over inhaled sevoflurane. Reassess protocols that promote volatile sedation in ARDS; consider potential harms despite logistical or environmental advantages.

Limitations

• Open-label sedation strategy could introduce performance bias despite assessor blinding
• Generalizability beyond French ICUs and to milder ARDS or different sedation protocols remains uncertain

Future Directions

Mechanistic studies to explain adverse outcomes with volatile sedation in ARDS and pragmatic trials testing protocolized sedation minimizing volatile agents.