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Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis

Gordon, AC; Perkins, GD; Singer, M; McAuley, DF; Orme, RML; Santhakumaran, S; Mason, AJ; ... Ashby, D; + view all (2016) Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis. The New England Journal of Medicine , 375 (17) pp. 1638-1648. 10.1056/NEJMoa1609409. Green open access

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Abstract

BACKGROUND: Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may improve outcomes in patients with sepsis. METHODS: We conducted a double-blind, randomized clinical trial to investigate whether levosimendan reduces the severity of organ dysfunction in adults with sepsis. Patients were randomly assigned to receive a blinded infusion of levosimendan (at a dose of 0.05 to 0.2 μg per kilogram of body weight per minute) for 24 hours or placebo in addition to standard care. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28 (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; maximum score, 20). Secondary outcomes included 28-day mortality, time to weaning from mechanical ventilation, and adverse events. RESULTS: The trial recruited 516 patients; 259 were assigned to receive levosimendan and 257 to receive placebo. There was no significant difference in the mean (±SD) SOFA score between the levosimendan group and the placebo group (6.68±3.96 vs. 6.06±3.89; mean difference, 0.61; 95% confidence interval [CI], −0.07 to 1.29; P=0.053). Mortality at 28 days was 34.5% in the levosimendan group and 30.9% in the placebo group (absolute difference, 3.6 percentage points; 95% CI, −4.5 to 11.7; P=0.43). Among patients requiring ventilation at baseline, those in the levosimendan group were less likely than those in the placebo group to be successfully weaned from mechanical ventilation over the period of 28 days (hazard ratio, 0.77; 95% CI, 0.60 to 0.97; P=0.03). More patients in the levosimendan group than in the placebo group had supraventricular tachyarrhythmia (3.1% vs. 0.4%; absolute difference, 2.7 percentage points; 95% CI, 0.1 to 5.3; P=0.04). CONCLUSIONS: The addition of levosimendan to standard treatment in adults with sepsis was not associated with less severe organ dysfunction or lower mortality. Levosimendan was associated with a lower likelihood of successful weaning from mechanical ventilation and a higher risk of supraventricular tachyarrhythmia. (Funded by the NIHR Efficacy and Mechanism Evaluation Programme and others; LeoPARDS Current Controlled Trials number, ISRCTN12776039.)

Type: Article
Title: Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1056/NEJMoa1609409
Publisher version: http://dx.doi.org/10.1056/NEJMoa1609409
Language: English
Additional information: From [Gordon, AC; Perkins, GD; Singer, M; McAuley, DF; Orme, RML; Santhakumaran, S; Mason, AJ; (2016) Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis. The New England Journal of Medicine , 375 (17) pp. 1638-1648. 10.1056/NEJMoa1609409]. Copyright © 2016 Massachusetts Medical Society. All rights reserved. Reprinted with permission.
Keywords: Science & Technology, Life Sciences & Biomedicine, Medicine, General & Internal, General & Internal Medicine, International Consensus Definitions, Randomized Controlled-trial, Septic Shock Sepsis-3, Acute Kidney Injury, Heart-failure, Critically Ill, Clinical-trial, Blood-pressure, Vasopressin, Norepinephrine
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1536325
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