{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T11:14:10Z","timestamp":1793445250024,"version":"4.5.0"},"reference-count":28,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"\n Importance<\/jats:title>\n Levosimendan may facilitate weaning from venoarterial extracorporeal membrane oxygenation (VA-ECMO) and improve survival, but supporting evidence remains limited.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To assess whether early administration of levosimendan reduces the time to successful VA-ECMO weaning in patients with severe but potentially reversible cardiogenic shock.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n Randomized, double-blind, placebo-controlled trial conducted across 11 intensive care units (ICUs) in France. Between August 27, 2021, and September 10, 2024, 205 adult patients with acute cardiogenic shock who had started VA-ECMO in the preceding 48 hours were enrolled. Final follow-up was completed on November 10, 2024.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Patients were randomized in a 1:1 ratio to receive levosimendan, 0.15 \u03bcg\/kg per minute, to be increased to 0.20 \u03bcg\/kg per minute after 2 hours (n\u2009=\u2009101), or placebo (n\u2009=\u2009104).<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was time to successful ECMO weaning within 30 days following randomization. Secondary outcomes included ECMO-, mechanical ventilation\u2013, and organ failure\u2013free days, ICU and hospital lengths of stay, serious adverse events, and all-cause 30- and 60-day mortality.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among the 205 randomized patients (median age, 58 [IQR, 50-67] years; 149 [72.7%] male), main cardiogenic shock etiologies were postcardiotomy (79 [38.5%]), acute myocardial infarction (56 [27.3%]), and myocarditis (28 [13.7%]). Treatment dose was increased to 0.20 \u00b1 0.01 \u03bcg\/kg per minute in 93% of patients receiving levosimendan and in 96% of those receiving placebo. Within 30 days, 69 of 101 patients (68.3%) had a successful ECMO weaning in the levosimendan group compared with 71 of 104 (68.3%) in the placebo group (risk difference, 0.0% [95% CI, \u221212.8% to 12.7%]; subdistribution hazard ratio, 1.02 [95% CI, 0.74-1.39];\n P<\/jats:italic>\n \u2009=\u2009.92). In the levosimendan and placebo groups, respectively, median ECMO duration (5 [IQR, 4-7] days vs 6 [IQR, 4-11] days;\n P<\/jats:italic>\n \u2009=\u2009.53), mean ICU length of stay (18 [SD, 15] days vs 19 [SD, 15] days;\n P<\/jats:italic>\n \u2009=\u2009.42), and 60-day mortality (27.7% vs 25.0%; risk difference, 2.7% [95% CI, \u22129.0% to 15.3%];\n P<\/jats:italic>\n \u2009=\u2009.78) did not differ significantly. Ventricular arrhythmias occurred more frequently with levosimendan (18 [17.8%] vs 9 [8.7%]; absolute risk difference, 9.2% [95% CI, 0.4%-18.1%]).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Among patients with severe but potentially reversible cardiogenic shock supported by VA-ECMO, early levosimendan administration did not significantly reduce the time to successful weaning of ECMO compared with placebo.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT04728932<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jama.2025.19843","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T16:00:23Z","timestamp":1764604823000},"page":"60","source":"Crossref","is-referenced-by-count":26,"title":["Levosimendan to Facilitate Weaning From ECMO in Patients With Severe Cardiogenic Shock"],"prefix":"10.1001","volume":"335","author":[{"given":"Alain","family":"Combes","sequence":"first","affiliation":[{"name":"INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, Sorbonne Universit\u00e9, Paris, France"},{"name":"AP-HP, Service de M\u00e9decine Intensive-R\u00e9animation, Institut de Cardiologie, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ouriel","family":"Saura","sequence":"additional","affiliation":[{"name":"INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, Sorbonne Universit\u00e9, Paris, France"},{"name":"AP-HP, Service de M\u00e9decine Intensive-R\u00e9animation, Institut de Cardiologie, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Nesseler","sequence":"additional","affiliation":[{"name":"INSERM, CIC 1414 (Centre d\u2019Investigation Clinique de Rennes), INRAE, INSERM, Institut NUMECAN\u2013UMR_A 1341, UMR_S 1241, Department of Anesthesia, Critical Care and Perioperative Medicine, Pontchaillou, University Hospital of Rennes, University of Rennes, CHU Rennes, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"Lebbah","sequence":"additional","affiliation":[{"name":"AP-HP, Unit\u00e9 de Recherche Clinique PSL-CFX, H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Rozec","sequence":"additional","affiliation":[{"name":"Service d\u2019Anesth\u00e9sie-R\u00e9animation, Nantes Universit\u00e9, CHU Nantes, H\u00f4pital La\u00ebnnec, Nantes, France"},{"name":"Nantes Universit\u00e9, CHU Nantes, CNRS, INSERM, l\u2019Institut du Thorax, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Levy","sequence":"additional","affiliation":[{"name":"M\u00e9decine 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Meslin","sequence":"additional","affiliation":[{"name":"AP-HP, Service d\u2019Anesth\u00e9sie-R\u00e9animation et M\u00e9decine Peri-Op\u00e9ratoire, H\u00f4pital Europ\u00e9en Georges Pompidou, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Gaudard","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Arnaud de Villeneuve, Montpellier University Hospital, University of Montpellier, and PhyMedExp, INSERM, CNRS, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrien","family":"Bougl\u00e9","sequence":"additional","affiliation":[{"name":"GRC 29, Groupe de Recherche Clinique en Anesth\u00e9sie R\u00e9animation M\u00e9decine P\u00e9riop\u00e9ratoire, ARPE, Sorbonne Universit\u00e9, Paris, France"},{"name":"APHP, DMU DREAM, Department of Anesthesiology and Critical 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