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The Effect of Selenium Therapy on Mortality in Patients With Sepsis Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials*

Alhazzani, Waleed MD1; Jacobi, Judith PharmD2; Sindi, Anees MD1; Hartog, Christiane MD3; Reinhart, Konrad MD3; Kokkoris, Stelios MB4; Gerlach, Herwig MD5; Andrews, Peter MD6; Drabek, Tomas MD7; Manzanares, William MD8; Cook, Deborah J. MD1,9; Jaeschke, Roman Z. MD1,9

doi: 10.1097/CCM.0b013e31828a24c6
Review Articles

Background: Patients with sepsis syndrome commonly have low serum selenium levels. Several randomized controlled trials have examined the efficacy of selenium supplementation on mortality in patients with sepsis.

Objective: To determine the efficacy and safety of high-dose selenium supplementation compared to placebo for the reduction of mortality in patients with sepsis.

Sources of Data: We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, SciFinder, and

Selection Criteria: Randomized controlled parallel group trials comparing selenium supplementation in doses greater than daily requirement to placebo on the outcome of mortality in patients with sepsis syndrome.

Data Collection and Analysis: Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcome was mortality; secondary outcomes were ICU length of stay, nosocomial pneumonia, and adverse events. Trial authors were contacted for additional or clarifying information.

Results: Nine trials enrolling a total of 792 patients were included. Selenium supplementation in comparison to placebo was associated with lower mortality (odds ratio, 0.73; 95% CI, 0.54, 0.98; p = 0.03; I 2 = 0%). Among patients receiving and not receiving selenium, there was no difference in ICU length of stay (mean difference, 2.03; 95% CI, –0.51, 4.56; p = 0.12; I 2 = 0%) or nosocomial pneumonia (odds ratio, 0.83; 95% CI, 0.28, 2.49; p = 0.74; I 2 = 56%). Significant heterogeneity among trials in adverse event reporting precluded pooling of results.

Conclusions: In patients with sepsis, selenium supplementation at doses higher than daily requirement may reduce mortality. We observed no impact of selenium on ICU length of stay or risk of nosocomial pneumonia.

1 Department of Medicine, McMaster University, Hamilton, ON, Canada.

2 Department of Pharmacy, Indiana University Health Methodist Hospital, Indianapolis, IN.

3 Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.

4 Department of Intensive Care, Western General Hospital, Edinburgh, UK.

5 Department of Anesthesia and Intensive Care, Vivantes–Klinikum Neukoelln, Berlin, Germany.

6 Department of Anesthesia, Critical Care and Pain Management, University of Edinburgh, Edinburgh, UK.

7 Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA.

8 Department of Critical Care, University Hospital Faculty of Medicine, Universidad de la República, Montevideo, Uruguay.

9 Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.

*See also p. 1591.

This work was performed at McMaster University.

Dr. Reinhart received grant support from and lectured for Biosyn. Dr. Drabek received grant support from The Laerdal Foundation for Acute Medicine, AHA #09BGIA2310196, and DoD81XWH-07-1-0682.

The remaining authors have disclosed that they do not have any potential conflicts of interest.

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© 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins