Sedation with isoflurane for patients receiving invasive ventilation in the intensive care unit (ICU) yielded a higher rate of spontaneous breathing and a shorter wakeup time than sedation with propofol, according to the results of a recent study published in Lancet Respiratory Medicine.

A European, phase 3, open-label noninferiority randomized controlled trial assessed the use of isoflurane vs propofol for sedation of invasively ventilated ICU patients in Germany and Slovenia. Patients were randomly assigned to isoflurane inhalation via an anaesthetic-conserving device or intravenous propofol infusion for 48 hours. The primary endpoint was percentage of time in Richmond Agitation–Sedation Scale (RASS) range –1 to –4. Secondary endpoints included opioid requirements, spontaneous breathing, time to wake-up, extubation, and adverse events.

Among the 388 patients enrolled, 301 patients were randomized 1:1 to either the isoflurane (n=150) or propofol (n=151) groups. A total of 146 patients in each group completed the 24 hours of follow-up. For the primary study outcome, the percentage of time in RASS target range was 90.7% in the isoflurane group and 91.1% in the propofol group. Additionally, the opioid dose intensity was 29% lower in the isoflurane group vs the propofol group. Other results included both more frequent spontaneous breathing on day 1 and shorter median wake up in the isoflurane group.

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The study authors wrote, “The main findings were that isoflurane, administered via the ACD for the sedation of patients in the ICU for up to 54 [hours], was efficacious, non-inferior to propofol, and well tolerated.” They added, “Sedation with isoflurane also resulted in a higher rate of spontaneous breathing, and a shorter wakeup time after 48 [hours] of study sedation, compared with propofol.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Meiser A, Volk T, Wallenborn J, et al. Inhaled isoflurane via the anaesthetic conserving device versus propofol for sedation of invasively ventilated patients in intensive care units in Germany and Slovenia: an open-label, phase 3, randomised controlled, non-inferiority trial. Lancet Respir Med. 2021;9(11):1231-1240. doi:10.1016/S2213-2600(21)00323-4