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.
| Specialty Area | Score |
|---|---|
| Respirology/Pulmonology | |
| Hospital Doctor/Hospitalists | |
| Internal Medicine | |
| Intensivist/Critical Care |
Although only some hospitalists will be managing sedation for patients with ARDS, the size of the observed difference in these patients is sufficient to continue my current preference for intravenous propofol over sevoflurane.
This trial can benefit Hospitalists working in an open ICU setting where they continue to provide care to patients transitioned to ICU level of care. In my mode of practice at my institution where I do not provide direct care to ICU patients as a hospitalist, I frequently provide care for post-ICU ARDS patients. Being up to date on the latest evidence pertaining to ARDS is helpful for transition of care and prognostic awareness. This is a multicenter assessor-blinded RCT with robust methodology. It is adequately powered for the primary end point of ventilator-free days at 28 days, but may have been underpowered to detect differences in longer-term outcomes (e.g., 90-day survival). A 2-day difference in ventilator-free days was statistically significant but may not be clinically significant, especially in severely ill ARDS patients. However, the study results are in line with the current ICU sedation guidelines that favor IV agents over inhaled agents.
There has been substantial interest in inhaled sedation as an alternative to continuous sedation infusions. This well done trial indicates that inhaled anesthetics are associated with worse outcomes. This is newsworthy but not directly relevant to practice because inhaled sedation is not currently standard of care.
Inhaled sedation in the ICU became a thing during the pandemic. Most don't have access to it; if there were positive studies, they would need to get access. This study shows potential harm, but the numbers are small. Bottom line - this is informative but not not practice-changing and more studies on the topic coming soon!
This is probably more relevant to Critical Care than Hospitalists.
This RCT finds that for ICU patients with ARDS, inhaled anesthesia with sevoflurane resulted in higher mortality and fewer ventilator-free days compared with IV propofol. This fails to provide support for inhaled anesthesia in this context.
This study suggests that ARDS patients sedated with inhaled sevoflurane had poorer survival than those sedated with propofol. The study was considerably limited by lack of data about fluid, steroid, and opioid administration.
The evidence for using inhaled anesthetics in ARDS had been scarce. This well-designed RCT puts the issue to rest with clear worsening outcomes in this cohort. Interesting question that required investigation.
ACP JournalWise is copyrighted © 2025 by the American College of Physicians
Powered by McMaster Premium Literature Service (PLUS)