Levosimendan in septic shock in patients with biochemical evidence of cardiac dysfunction: a subgroup analysis of the LeoPARDS randomised trial

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Title: Levosimendan in septic shock in patients with biochemical evidence of cardiac dysfunction: a subgroup analysis of the LeoPARDS randomised trial
Authors: Antcliffe, DB
Santhakumaran, S
Orme, RML
Ward, JK
Al-Beidh, F
O’Dea, K
Perkins, GD
Singer, M
McAuley, DF
Mason, AJ
Cross, M
Ashby, D
Gordon, AC
Item Type: Journal Article
Abstract: Purpose Myocardial dysfunction is common in sepsis but optimal treatment strategies are unclear. The inodilator, levosimendan was suggested as a possible therapy; however, the levosimendan to prevent acute organ dysfunction in Sepsis (LeoPARDS) trial found it to have no benefit in reducing organ dysfunction in septic shock. In this study we evaluated the effects of levosimendan in patients with and without biochemical cardiac dysfunction and examined its non-inotropic effects. Methods Two cardiac biomarkers, troponin I (cTnI) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and five inflammatory mediators were measured in plasma from patients recruited to the LeoPARDS trial at baseline and over the first 6 days. Mean total Sequential Organ Failure Assessment (SOFA) score and 28-day mortality were compared between patients with normal and raised cTnI and NT-proBNP values, and between patients above and below median values. Results Levosimendan produced no benefit in SOFA score or 28-day mortality in patients with cardiac dysfunction. There was a statistically significant treatment by subgroup interaction (p = 0.04) in patients with NT-proBNP above or below the median value. Those with NT-proBNP values above the median receiving levosimendan had higher SOFA scores than those receiving placebo (mean daily total SOFA score 7.64 (4.41) vs 6.09 (3.88), mean difference 1.55, 95% CI 0.43–2.68). Levosimendan had no effect on the rate of decline of inflammatory biomarkers. Conclusion Adding levosimendan to standard care in septic shock was not associated with less severe organ dysfunction nor lower mortality in patients with biochemical evidence of cardiac dysfunction.
Issue Date: Oct-2019
Date of Acceptance: 5-Aug-2019
URI: http://hdl.handle.net/10044/1/72773
DOI: https://doi.org/10.1007/s00134-019-05731-w
ISSN: 0342-4642
Publisher: Springer Science and Business Media LLC
Start Page: 1392
End Page: 1400
Journal / Book Title: Intensive Care Medicine
Volume: 45
Issue: 10
Copyright Statement: © Springer-Verlag GmbH Germany, part of Springer Nature 2019. The final publication is available at Springer via https://doi.org/10.1007/s00134-019-05731-w
Sponsor/Funder: National Institute for Health Research
National Institute for Health Research
National Institute for Health Research
Tenax Therapeutics Inc
Funder's Grant Number: NIHR/CS/009/007
NIHR Fellowship
11/14/08
WSSA_P52845
Keywords: Inflammation
Levosimendan
N-terminal prohormone of brain natriuretic peptide
Septic shock
Troponin
cTnI
Emergency & Critical Care Medicine
1103 Clinical Sciences
1117 Public Health and Health Services
Publication Status: Published
Embargo Date: 2020-08-19
Online Publication Date: 2019-08-19
Appears in Collections:Division of Surgery
Faculty of Medicine
Epidemiology, Public Health and Primary Care



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