Summary of “Inhaled Sedation in Acute Respiratory Distress Syndrome: The SESAR Randomized Clinical Trial”
Abstract
This randomized clinical trial compared the efficacy and safety of inhaled sevoflurane versus intravenous propofol for sedation in patients with moderate to severe acute respiratory distress syndrome (ARDS). Conducted across 37 French ICUs, the study enrolled 687 patients to determine whether inhaled sedation improved ventilator-free days at 28 days and 90-day survival. The results showed that sevoflurane led to fewer ventilator-free days and lower survival rates compared to propofol. These findings do not support the routine use of inhaled sedation with sevoflurane in critically ill ARDS patients.
Key Points
-
Study Design and Participants: This was a phase 3, open-label, assessor-blinded trial enrolling 687 patients with early moderate to severe ARDS (PaO₂/FiO₂ <150 mmHg, PEEP ≥8 cmH₂O). Patients were randomized to receive either inhaled sevoflurane or intravenous propofol for up to seven days.
-
Primary Endpoint – Ventilator-Free Days at 28 Days: The median number of ventilator-free days was 0.0 in both groups, but the interquartile range favored propofol (0.0 to 18.7 days) over sevoflurane (0.0 to 11.9 days), with a median difference of -2.1 days.
-
90-Day Mortality Outcomes: Survival at 90 days was significantly lower in the sevoflurane group (47.1%) compared to the propofol group (55.7%), with a hazard ratio of 1.31, indicating a 31% higher risk of mortality with inhaled sedation.
-
Short-Term Mortality Differences: Sevoflurane was associated with higher 7-day mortality (19.4% vs. 13.5%, relative risk 1.44), suggesting early adverse effects that contributed to worse outcomes.
-
Hemodynamic and Renal Effects: Patients in the sevoflurane group required higher norepinephrine doses and had increased lactate levels, possibly indicating vasodilatory shock. Additionally, they were more likely to develop acute kidney injury.
-
Impact of COVID-19 Subgroup: Patients with ARDS due to COVID-19 showed a greater disparity in mortality outcomes between sevoflurane and propofol, suggesting a differential effect based on ARDS etiology.
-
Ventilation Strategies and Adverse Events: Both groups received lung-protective ventilation and similar neuromuscular blockade protocols. Sevoflurane was associated with an increased risk of nephrogenic diabetes insipidus.
-
No Improvement in Oxygenation: Contrary to prior hypotheses, inhaled sevoflurane did not confer an oxygenation benefit, challenging previous data suggesting volatile anesthetics improve pulmonary function.
-
Potential Mechanisms for Worse Outcomes: The increased mortality and lower ventilator-free days may be linked to sevoflurane-induced hemodynamic instability, impaired CO₂ clearance due to dead space accumulation, and increased renal dysfunction.
-
Implications for ARDS Sedation: The results suggest that intravenous propofol remains the preferred sedation strategy in ARDS, with inhaled sevoflurane showing no advantage and potential harm.
Conclusion
In patients with moderate to severe ARDS, inhaled sedation with sevoflurane resulted in fewer ventilator-free days and lower 90-day survival compared to intravenous sedation with propofol. These findings do not support the routine use of inhaled sevoflurane in ARDS management and highlight potential safety concerns, including hemodynamic instability and increased risk of acute kidney injury. Future research should focus on refining sedation strategies tailored to specific ARDS subgroups while balancing respiratory, hemodynamic, and renal considerations.
Watch the following video on “Respiratory drive ESICM vebinar 2024” by nsicu ru
***FREE ACCESS ARTICLE***
Jabaudon M, Quenot J, Badie J, et al. Inhaled Sedation in Acute Respiratory Distress Syndrome: The SESAR Randomized Clinical Trial. JAMA. Published online March 18, 2025. doi:10.1001/jama.2025.3169
