Isoflurane-Based Inhaled Sedation in Mechanically Ventilated Adults With Acute Hypoxemic Respiratory Failure: The SAVE-ICU Randomized Clinical Trial
JAMA, 2026 · Pragmatic open-label randomized trial in 14 Canadian ICUs; 780 in the primary analysis
What the trial found
Hospital mortality was 42.5% versus 43.8% (RR 0.98, 95% CI 0.84–1.14); ventilator-free days were similar. The inhaled strategy used more hypoxemia adjuncts and yielded fewer delirium- and coma-free days.
Current guideline position
This trial must be interpreted alongside indication-specific guidance; its result alone does not establish a universal treatment policy.
Clinical interpretation
Do not promise an outcome advantage from routine inhaled sedation in hypoxemic respiratory failure.
Limitations
Analgesia-first sedation, light sedation targets, ABCDEF bundle, spontaneous breathing trials, and non-pharmacologic delirium mitigation.
Acute, diffuse inflammatory lung injury causing hypoxemia and bilateral infiltrates not fully explained by cardiac failure or fluid overload.
Pathophysiologic mechanisms (shunt vs V/Q mismatch), dynamic ROX index trajectories, P-SILI prevention, and evidence-based oxygen escalation ladders.
Complete clinical topic overview. For the full 10-level interactive course, visit Master MV. Covers core ventilator modes, respiratory mechanics (Cstat, Raw, driving pressure), waveform dyssynchrony analysis, VILI prevention, and liberation protocols.