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Levosimendan in septic shock in patients with biochemical evidence of cardiac dysfunction : a subgroup analysis of the LeoPARDS randomised trial
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Antcliffe, David B., Santhakumaran, Shalini, Ormec, Robert M. L., Ward, Josie K., Al-Beidh, Farah, O'Dea, Kieran, Perkins, Gavin D., Singer, Mervyn, McAuley, Daniel F., Mason, Alexina, Cross, Mary, Ashby, Deborah and Gordon, Anthony C. (2019) Levosimendan in septic shock in patients with biochemical evidence of cardiac dysfunction : a subgroup analysis of the LeoPARDS randomised trial. Intensive Care Medicine, 45 . pp. 1392-1400. doi:10.1007/s00134-019-05731-w ISSN 0342-4642.
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WRAP-Levosimendan-septic-shock-patients-biochemical-dysfunction-Perkins-2019.pdf - Accepted Version - Requires a PDF viewer. Download (857Kb) | Preview |
Official URL: https://doi.org/10.1007/s00134-019-05731-w
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.
| Item Type: | Journal Article | |||||||||||||||
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| Subjects: | R Medicine > RC Internal medicine | |||||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Clinical Trials Unit Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Septicemia, Septicemia -- Patients, Heart -- Diseases -- Diagnosis, Biochemical markers | |||||||||||||||
| Journal or Publication Title: | Intensive Care Medicine | |||||||||||||||
| Publisher: | Springer | |||||||||||||||
| ISSN: | 0342-4642 | |||||||||||||||
| Official Date: | October 2019 | |||||||||||||||
| Dates: |
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| Volume: | 45 | |||||||||||||||
| Page Range: | pp. 1392-1400 | |||||||||||||||
| DOI: | 10.1007/s00134-019-05731-w | |||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||
| Publication Status: | Published | |||||||||||||||
| Reuse Statement (publisher, data, author rights): | This is a post-peer-review, pre-copyedit version of an article published in Intensive Care Medicine. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00134-019-05731-w | |||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||
| Date of first compliant deposit: | 8 August 2019 | |||||||||||||||
| Date of first compliant Open Access: | 19 August 2020 | |||||||||||||||
| RIOXX Funder/Project Grant: |
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