Inhaled Sedation in Acute Respiratory Distress Syndrome: The SESAR Randomized Clinical Trial.
Summary
In this phase 3 randomized, assessor-blinded trial of 687 ARDS patients, inhaled sevoflurane sedation led to fewer ventilator‑free days by day 28 and lower 90‑day survival compared with intravenous propofol. Early 7‑day mortality and ICU‑free days were also worse with sevoflurane.
Key Findings
- Sevoflurane resulted in fewer ventilator‑free days at day 28 vs propofol (median difference −2.1 days, 95% CI −3.6 to −0.7).
- 90‑day survival was lower with sevoflurane (47.1%) than propofol (55.7%; HR 1.31, 95% CI 1.05–1.62).
- Higher 7‑day mortality and fewer ICU‑free days through day 28 occurred with sevoflurane.
Clinical Implications
For moderate-to-severe ARDS requiring deep sedation, prioritize intravenous propofol over inhaled sevoflurane outside of research protocols; review institutional sedation pathways and device availability. Monitor for early mortality risk when using inhaled agents.
Why It Matters
This high‑quality RCT directly informs sedation choice in ARDS and indicates potential harm with inhaled sevoflurane. The negative but definitive findings can change ICU practice and guidelines.
Limitations
- Open-label to treating teams may introduce performance bias
- Results reflect French ICUs and device availability; generalizability to other settings may vary
Future Directions
Conduct pragmatic trials on sedation bundles incorporating analgesia-first strategies; explore mechanistic reasons for harm with volatile agents in ARDS (e.g., alveolar inflammation, hemodynamics).
Study Information
- Study Type
- RCT
- Research Domain
- Treatment
- Evidence Level
- I - High-quality randomized clinical trial evidence directly comparing sedation strategies.
- Study Design
- OTHER