Inhaled Isoflurane Sedation in the ICU: What SAVE-ICU Showed
Volatile anesthetics are our everyday tools in the OR, so there has been real interest in bringing them to the ICU for sedation. The SAVE-ICU trial, published October 14, 2026 in JAMA, is the largest randomized test of that idea so far in patients on the ventilator with acute hypoxemic respiratory failure.
The study
This was a pragmatic, open-label trial in 14 Canadian ICUs. Adults on mechanical ventilation for hypoxemic respiratory failure, either COVID-19 or other causes, were randomized early to an isoflurane-based inhaled sedation strategy with IV adjuncts as needed, or to usual IV sedation. About 780 patients were analyzed. Roughly half of the inhaled group still received some IV sedation on any given day in the first two weeks.
Hospital mortality was 42.5% with inhaled sedation and 43.8% with IV sedation, with no significant difference. ICU free days, ventilator free days, hospital free days, and three month quality of life and disability scores were similar. The inhaled group received more rescue therapies for hypoxemia and had fewer delirium and coma free days, largely from more time in coma.
Why it matters
The hope behind inhaled sedation has been that faster offset and possible lung protective effects would translate into better outcomes. SAVE-ICU does not show that. It also did not show the mortality harm seen in the earlier SESAR trial with sevoflurane, which is reassuring on safety, although the accompanying editorial points out that kidney and liver labs were not collected prospectively, so organ safety is not fully settled.
The deeper sedation finding is the part I keep coming back to. Many patients in the isoflurane group were deeply sedated in the first days, and more than half of all patients were also receiving neuromuscular blockade, which makes bedside sedation scores hard to use. Volatile agents are easy to titrate when you are watching end-tidal concentration closely, as we do in the OR. Without that kind of monitoring and experience, it is easy to end up deeper than intended.
What it means for practice here
For now, I do not see this trial as a reason to change how most ventilated patients are sedated. Light sedation goals, daily reassessment, and attention to delirium still matter more than the choice of agent. If inhaled sedation is used, it should come with the same discipline we use in the OR: monitored end-tidal levels, a clear target, and a plan to lighten up as soon as the patient allows.
Source
- Jerath A, Slessarev M, Martin C, et al. Isoflurane-based inhaled sedation in mechanically ventilated adults with acute hypoxemic respiratory failure: the SAVE-ICU randomized clinical trial. JAMA. Published online October 14, 2026. doi:10.1001/jama.2026.18471. Article (JAMA)
This post is clinician commentary for educational discussion. It is not medical advice for any reader's personal care. Anesthesia and perioperative decisions should be made with the treating clinician based on the individual patient's circumstances.