{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:52:34Z","timestamp":1791985954788,"version":"4.4.0"},"reference-count":42,"publisher":"American Medical Association (AMA)","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"abstract":"\n Importance<\/jats:title>\n Rigorous evidence for inhaled sedation using isoflurane in mechanically ventilated patients with acute hypoxemic respiratory failure (AHRF) is limited.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate whether an inhaled sedation strategy lowers hospital mortality compared with usual care intravenous sedation strategy in mechanically ventilated adults with AHRF.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n Pragmatic, effectiveness, open-label, superiority, randomized clinical trial in 14 intensive care units (ICUs) in Canada. Adults (\u226518 years) receiving sedation for less than 72 hours and receiving mechanical ventilation for AHRF from non-COVID respiratory failure (ratio of partial pressure of arterial oxygen [Pa\n o<\/jats:sc>\n 2<\/jats:sub>\n ] to fraction of inspired oxygen [F\n io<\/jats:sc>\n 2<\/jats:sub>\n ] &amp;lt;300 mm Hg) or COVID-19 were enrolled between September 2020 and March 2025 with follow-up through June 2025.\n <\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n Patients were randomized to an inhaled sedation strategy using isoflurane with intravenous adjuncts as clinically needed or to a usual intravenous sedation care strategy. Sedatives were titrated to achieve the desired target sedation score guided by clinical teams and continued until extubation or death.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Primary outcome was all-cause hospital mortality. Secondary outcomes included ICU- and ventilator-free days at day 30; hospital-free days at day 60; use of refractory hypoxemia adjunctive therapies; delirium- and coma-free days at day 14; and quality-of-life and disability scores at 3 months.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 786 patients randomized, 780 were included in the primary analysis (mean age, 61.1 years; 34.0% female; 73.7% non-COVID AHRF, mean Pa\n o<\/jats:sc>\n 2<\/jats:sub>\n :F\n io<\/jats:sc>\n 2<\/jats:sub>\n ratio, 152.6 mm Hg); 385 in the inhaled sedation and 395 in the intravenous sedation groups. In the inhaled sedation group, 49.9% to 55.4% of patients received concomitant intravenous sedation on any day during the first 14 days after randomization. At hospital discharge, 161 of 379 patients (42.5%) in the inhaled sedation group had died, compared with 171 of 390 patients (43.8%) in the intravenous sedation group (risk ratio, 0.98 [95% CI, 0.84 to 1.14];\n P<\/jats:italic>\n \u2009=\u2009.85). There was no effect modification in prespecified subgroup analyses for age, sex, and COVID-19 status. ICU-, ventilator-, and hospital-free days were similar between groups. The inhaled sedation group received more adjunctive therapies for hypoxemia (239 [63.9%] vs 214 [55.0%]; between-group difference, 8.89% [95% CI, 1.95% to 15.83%]) and had fewer delirium- and coma-free days (between-group difference, \u22120.95 [95% CI, \u22121.69 to \u22120.22]). There was no difference in quality-of-life and disability scores between groups.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In mechanically ventilated adults with AHRF, an inhaled sedation strategy using isoflurane with intravenous adjuncts as clinically needed did not reduce hospital mortality compared with an intravenous sedation strategy.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT04415060<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jama.2026.18471","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:30:21Z","timestamp":1791984621000},"source":"Crossref","is-referenced-by-count":0,"title":["Isoflurane-Based Inhaled Sedation in Mechanically Ventilated Adults With Acute Hypoxemic Respiratory Failure"],"prefix":"10.1001","author":[{"given":"Angela","family":"Jerath","sequence":"first","affiliation":[{"name":"Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada"},{"name":"Temerty Faculty of Medicine, Department of Anesthesiology and Pain Medicine, Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada"},{"name":"Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marat","family":"Slessarev","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre Research Institute, London, Ontario, Canada"},{"name":"Department of Medicine, Western University, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Martin","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre Research Institute, London, Ontario, Canada"},{"name":"Department of Medicine, Western University, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9rick","family":"D\u2019Aragon","sequence":"additional","affiliation":[{"name":"Department of anesthesiology, Universit\u00e9 de Sherbrooke, Sherbrooke, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois Martin","family":"Carrier","sequence":"additional","affiliation":[{"name":"Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM), Montr\u00e9al, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janek","family":"Senaratne","sequence":"additional","affiliation":[{"name":"Grey Nuns Community Hospital, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary","family":"Meggison","sequence":"additional","affiliation":[{"name":"The Ottawa Hospital, University Health Network, Ottawa, Ontario, 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