Isoflurane Sedation Did Not Reduce Hospital Mortality in Acute Hypoxemic Respiratory Failure

A JAMA-reported pragmatic, open-label randomized superiority trial evaluated isoflurane-based inhaled sedation versus usual intravenous sedation in mechanically ventilated adults with acute hypoxemic respiratory failure. Conducted in 14 Canadian ICUs, the trial enrolled 786 patients between September 2020 and March 2025; 780 entered the primary analysis. Mean age was 61.1 years, and 73.7% had non-COVID respiratory failure. The primary outcome was all-cause hospital mortality.

Hospital mortality was 42.5% (161/379) with inhaled sedation and 43.8% (171/390) with intravenous sedation (risk ratio, 0.98; 95% CI, 0.84–1.14; P=.85). ICU-, ventilator-, and hospital-free days were similar. More patients receiving inhaled sedation required adjunctive hypoxemia therapies (63.9% vs 55.0%; difference, 8.89 percentage points; 95% CI, 1.95–15.83), and they had fewer delirium- and coma-free days at day 14 (difference, −0.95 days; 95% CI, −1.69 to −0.22). Quality-of-life and disability scores did not differ at three months.

These findings do not support choosing isoflurane-based sedation to reduce hospital mortality in this population, although the confidence interval does not establish equivalence. Interpretation should account for the open-label design and concomitant intravenous sedation in 49.9%–55.4% of the inhaled group on any given day during the first 14 days. The trial therefore assessed a sedation strategy rather than isoflurane alone; full-text details were unavailable for this update.