{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:02:55Z","timestamp":1793329375234,"version":"4.5.0"},"reference-count":38,"publisher":"American Medical Association (AMA)","issue":"18","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2025,5,13]]},"abstract":"<jats:sec><jats:title>Importance<\/jats:title><jats:p>Whether the use of inhaled or intravenous sedation affects outcomes differentially in mechanically ventilated adults with acute respiratory distress syndrome (ARDS) is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the efficacy and safety of inhaled sevoflurane compared with intravenous propofol for sedation in patients with ARDS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>Phase 3 randomized, open-label, assessor-blinded clinical trial conducted from May 2020 to October 2023 with 90-day follow-up. Adults with early moderate to severe ARDS (defined by a ratio of Pao<jats:sub>2<\/jats:sub> to the fraction of inspired oxygen of &amp;amp;lt;150 mm Hg with a positive end-expiratory pressure of \u22658 cm H<jats:sub>2<\/jats:sub>O) were enrolled in 37 French intensive care units.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interventions<\/jats:title><jats:p>Patients were randomized to a strategy of inhaled sedation with sevoflurane (intervention group) or to a strategy of intravenous sedation with propofol (control group) for up to 7 days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The primary end point was the number of ventilator-free days at 28 days; the key secondary end point was 90-day survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 687 patients enrolled (mean [SD] age, 65 [12] years; 30% female), 346 were randomized to sevoflurane and 341 to propofol. The median total duration of sedation was 7 days (IQR, 4 to 7) in both groups. The number of ventilator-free days through day 28 was 0.0 days (IQR, 0.0 to 11.9) in the sevoflurane group and 0.0 days (IQR, 0.0 to 18.7) in the propofol group (median difference, \u22122.1 [95% CI, \u22123.6 to \u22120.7]; standardized hazard ratio, 0.76 [95% CI, 0.50 to 0.97]). The 90-day survival rates were 47.1% and 55.7% in the sevoflurane and propofol groups, respectively (hazard ratio, 1.31 [95% CI, 1.05 to 1.62]). Among 4 secondary outcomes, sevoflurane was associated with higher 7-day mortality (19.4% vs 13.5%, respectively; relative risk, 1.44 [95% CI, 1.02 to 2.03]) and fewer intensive care unit\u2013free days through day 28 (median, 0.0 [IQR, 0.0 to 6.0] vs 0.0 [IQR, 0.0 to 15.0]; median difference, \u20132.5 [95% CI, \u20133.7 to \u20131.4]) compared with propofol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Relevance<\/jats:title><jats:p>Among patients with moderate to severe ARDS, inhaled sedation with sevoflurane resulted in fewer ventilator-free days at day 28 and lower 90-day survival than sedation with propofol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04235608\">NCT04235608<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jama.2025.3169","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T08:30:33Z","timestamp":1742286633000},"page":"1608","source":"Crossref","is-referenced-by-count":64,"title":["Inhaled Sedation in Acute Respiratory Distress Syndrome"],"prefix":"10.1001","volume":"333","author":[{"given":"Matthieu","family":"Jabaudon","sequence":"first","affiliation":[{"name":"Department of Perioperative Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France"},{"name":"iGReD, CNRS, INSERM, Universit\u00e9 Clermont Auvergne, Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Quenot","sequence":"additional","affiliation":[{"name":"The Lipness Team, INSERM Lipids, Nutrition, Cancer-Unit\u00e9 Mixte de Recherche 1231 and LabEx LipSTIC, INSERM Centre d\u2019Investigation Clinique 1432, Clinical Epidemiology, Universit\u00e9 de Bourgogne, and M\u00e9decine Intensive R\u00e9animation, CHU Dijon, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Badie","sequence":"additional","affiliation":[{"name":"R\u00e9animation Polyvalente, H\u00f4pital Nord Franche-Comt\u00e9, Tr\u00e9venans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jules","family":"Audard","sequence":"additional","affiliation":[{"name":"Department of Perioperative Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Jaber","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire (CHU) Montpellier, D\u00e9partement Anesth\u00e9sie R\u00e9animation B, H\u00f4pital Saint Eloi and PhyMedExp, INSERM U1046, Universit\u00e9 de Montpellier, Montpellier, 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