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01-10-2019 | Septicemia | Original

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

Authors: David B. Antcliffe, Shalini Santhakumaran, Robert M. L. Orme, Josie K. Ward, Farah Al-Beidh, Kieran O’Dea, Gavin D. Perkins, Mervyn Singer, Daniel F. McAuley, Alexina J. Mason, Mary Cross, Deborah Ashby, Anthony C. Gordon

Published in: Intensive Care Medicine | Issue 10/2019

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.

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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: David B. Antcliffe
Shalini Santhakumaran
Robert M. L. Orme
Josie K. Ward
Farah Al-Beidh
Kieran O’Dea
Gavin D. Perkins
Mervyn Singer
Daniel F. McAuley
Alexina J. Mason
Mary Cross
Deborah Ashby
Anthony C. Gordon
Publication date: 01-10-2019
Publisher: Springer Berlin Heidelberg
Keywords: Septicemia
Septicemia
Septic Shock
Biomarkers
Published in: Intensive Care Medicine / Issue 10/2019
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-019-05731-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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