A randomized clinical trial involving 687 adult patients with moderate to severe acute respiratory distress syndrome found that inhaled sevoflurane could result in fewer ventilator-free days and lower 90-day survival compared with intravenous propofol.

Conducted in 37 intensive care units (ICU) across France, researchers assigned 346 patients to receive sevoflurane and 341 to receive propofol for sedation during the first 7 days of mechanical ventilation.

The primary outcome was ventilator-free days within 28 days of randomization. Both groups had a median of 0.0 days, but the propofol group had a broader interquartile range ([IQR] = 0.0–18.7) compared with the sevoflurane group (IQR = 0.0–11.9). The median difference was −2.1 days (95% confidence interval [CI] = −3.6 to −0.7), favoring propofol.

Ninety-day survival was 47.1% in the sevoflurane group and 55.7% in the propofol group. The hazard ratio for mortality was 1.31 (95% CI = 1.05–1.62), indicating higher mortality with sevoflurane. At 7 days, mortality was also higher with sevoflurane (19.4% vs 13.5%, relative risk = 1.44, 95% CI = 1.02–2.03).

The number of ICU-free days by day 28 also differed. Both groups had a median of 0.0, but the upper range was lower in the sevoflurane group (IQR = 0.0–6.0) compared with in the propofol group (IQR = 0.0–15.0), with a median difference of −2.5 days (95% CI = −3.7 to −1.4).

Acute kidney injury was more frequent in the sevoflurane group. Stage III kidney injury occurred in 33.5% of these patients compared with 27.0% among those in the propofol group. Just 31.8% of the patients who received sevoflurane remained free of kidney injury through day 7 vs 42.8% of those who received propofol. Nephrogenic diabetes insipidus was reported among five patients receiving sevoflurane and none receiving propofol.

The median PaO₂/FiO₂ ratio at enrollment was similar between groups (111 mmHg for sevoflurane, 107 mmHg for propofol). About 55% of patients had COVID-19 pneumonia as the underlying acute respiratory distress syndrome cause. Sedation depth, neuromuscular blockade, and ventilation strategies were standardized across groups.

The trial took place from May 2020 to October 2023. Informed consent was obtained from all participants or their representatives. The researchers noted that further investigation is needed to assess the effects of other volatile agents or shorter durations of inhaled sedation.

Full author disclosures are available in the source publication.

Source: JAMA