Original Investigation 

Caring for the Critically Ill Patient

March 18, 2025

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

Matthieu Jabaudon, Jean-Pierre Quenot, Julio Badie, et al

JAMA. Published online March 18, 2025. doi:10.1001/jama.2025.3169

Key Points

Question  Is a strategy of inhaled sedation with sevoflurane safe and associated with improved clinical outcomes in patients with acute respiratory distress syndrome compared with a strategy of intravenous sedation with propofol?

Findings  In this randomized clinical trial that included 687 intensive care unit patients with moderate to severe acute respiratory distress syndrome, inhaled sedation with sevoflurane resulted in fewer ventilator-free days at 28 days and lower survival at 90 days than intravenous sedation with propofol.

Meaning  These findings do not support a strategy of inhaled sedation with sevoflurane in critically ill patients with moderate to severe acute respiratory distress syndrome.

Abstract

Importance  Whether the use of inhaled or intravenous sedation affects outcomes differentially in mechanically ventilated adults with acute respiratory distress syndrome (ARDS) is unknown.

Objective  To determine the efficacy and safety of inhaled sevoflurane compared with intravenous propofol for sedation in patients with ARDS.

Design, Setting, and Participants  Phase 3 randomized, open-label, assessor-blinded clinical trial conducted from May 2020 to October 2023 with 90-day follow-up. Adults with early moderate to severe ARDS (defined by a ratio of Pao₂ to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure of ≥8 cm H₂O) were enrolled in 37 French intensive care units.

Interventions  Patients were randomized to a strategy of inhaled sedation with sevoflurane (intervention group) or to a strategy of intravenous sedation with propofol (control group) for up to 7 days.

Main Outcomes and Measures  The primary end point was the number of ventilator-free days at 28 days; the key secondary end point was 90-day survival.

Results  Of 687 patients enrolled (mean [SD] age, 65 [12] years; 30% female), 346 were randomized to sevoflurane and 341 to propofol. The median total duration of sedation was 7 days (IQR, 4 to 7) in both groups. The number of ventilator-free days through day 28 was 0.0 days (IQR, 0.0 to 11.9) in the sevoflurane group and 0.0 days (IQR, 0.0 to 18.7) in the propofol group (median difference, −2.1 [95% CI, −3.6 to −0.7]; standardized hazard ratio, 0.76 [95% CI, 0.50 to 0.97]). The 90-day survival rates were 47.1% and 55.7% in the sevoflurane and propofol groups, respectively (hazard ratio, 1.31 [95% CI, 1.05 to 1.62]). Among 4 secondary outcomes, sevoflurane was associated with higher 7-day mortality (19.4% vs 13.5%, respectively; relative risk, 1.44 [95% CI, 1.02 to 2.03]) and fewer intensive care unit–free days through day 28 (median, 0.0 [IQR, 0.0 to 6.0] vs 0.0 [IQR, 0.0 to 15.0]; median difference, –2.5 [95% CI, –3.7 to –1.4]) compared with propofol.

Conclusions and Relevance  Among patients with moderate to severe ARDS, inhaled sedation with sevoflurane resulted in fewer ventilator-free days at day 28 and lower 90-day survival than sedation with propofol.

Trial Registration  ClinicalTrials.gov Identifier: NCT04235608