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Prior Use of Calcium Channel Blockers Is Associated With Decreased Mortality in Critically Ill Patients With Sepsis: A Prospective Observational Study

Wiewel, Maryse A. MD; van Vught, Lonneke A. MD; Scicluna, Brendon P. PhD; Hoogendijk, Arie J. PhD; Frencken, Jos F. MD; Zwinderman, Aeilko H. PhD; Horn, Janneke MD, PhD; Cremer, Olaf L. MD, PhD; Bonten, Marc J. MD, PhD; Schultz, Marcus J. MD, PhD; van der Poll, Tom MD, PhD; on behalf of the Molecular Diagnosis and Risk Stratification of Sepsis (MARS) Consortium

doi: 10.1097/CCM.0000000000002236
Clinical Investigations
Editor's Choice

Objectives: Experimental studies suggest that calcium channel blockers can improve sepsis outcome. The aim of this study was to determine the association between prior use of calcium channel blockers and the outcome of patients admitted to the ICU with sepsis.

Design: A prospective observational study.

Setting: The ICUs of two tertiary care hospitals in the Netherlands.

Patients: In total, 1,060 consecutive patients admitted with sepsis were analyzed, 18.6% of whom used calcium channel blockers.

Interventions: None.

Measurements and Main Results: Considering large baseline differences between calcium channel blocker users and nonusers, a propensity score matched cohort was constructed to account for differential likelihoods of receiving calcium channel blockers. Fifteen plasma biomarkers providing insight in key host responses implicated in sepsis pathogenesis were measured during the first 4 days after admission. Severity of illness over the first 24 hours, sites of infection and causative pathogens were similar in both groups. Prior use of calcium channel blockers was associated with improved 30-day survival in the propensity-matched cohort (20.2% vs 32.9% in non-calcium channel blockers users; p = 0.009) and in multivariate analysis (odds ratio, 0.48; 95% CI, 0.31–0.74; p = 0.0007). Prior calcium channel blocker use was not associated with changes in the plasma levels of host biomarkers indicative of activation of the cytokine network, the vascular endothelium and the coagulation system, with the exception of antithrombin levels, which were less decreased in calcium channel blocker users.

Conclusions: Prior calcium channel blocker use is associated with reduced mortality in patients following ICU admission with sepsis.

1Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

2The Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

3Department of Clinical Epidemiology, Bioinformatics, and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

4Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

5Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

6Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.

7Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.

8Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.

A complete list of members of the Molecular Diagnosis and Risk Stratification of Sepsis Consortium appears in the Acknowledgements.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

This research was performed within the framework of the Center for Translational Molecular Medicine (CTMM) (www.ctmm.nl), project Molecular Diagnosis and Risk Stratification of Sepsis (grant 04I-201). The sponsor CTMM was not involved in the design and conduction of the study; nor was the sponsor involved in collection, management, analysis, and interpretation of the data or preparation, review or approval of the article. Decision to submit the article was not dependent on the sponsor.

Dr. Cremer’s institution received funding from Center for Translational Molecular Medicine, project Molecular Diagnosis and Risk Stratification of Sepsis. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: m.a.wiewel@amc.uva.nl

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