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Original Investigation
September 2016

Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic ShockA Randomized Clinical Trial

Author Affiliations
  • 1Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany
  • 2Center for Sepsis Control & Care, Jena University Hospital, Jena, Germany
  • 3Clinical Trial Centre Leipzig, University of Leipzig, Leipzig, Germany
  • 4Department of Intensive Care Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany
  • 5Department of Anesthesiology, University Hospital Munich, Munich, Germany
  • 6Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario, Canada
  • 7Department of Anesthesiology and Surgical Intensive Care Medicine, Hospital Augsburg, Augsburg, Germany
  • 8Department of Anesthesiology, University Hospital Göttingen, Göttingen, Germany
  • 9Department of Anesthesiology and Intensive Care Medicine, University Hospital Oldenburg, Oldenburg, Germany
  • 10Department of Intensive Care Medicine, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany
  • 11Department of Anesthesiology and Intensive Care Medicine, University Hospital Greifswald, Germany
  • 12Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt, Germany
  • 13Department of Nephrology and Intensive Care Medicine, Charité Berlin, Berlin, Germany
  • 14Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, HELIOS Hospital Erfurt, Erfurt, Germany
  • 15Department of General Surgery, University Hospital Freiburg, Freiburg, Germany
  • 16Department of Anesthesiology and Intensive Care Medicine, University Hospital Leipzig, Leipzig, Germany
  • 17Department of Anesthesiology and Surgical Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
  • 18Department of Anesthesiology and Intensive Care Medicine, University Medical Center Kiel, Kiel, Germany
  • 19Department of Anesthesiology and Intensive Care Medicine, University Hospital Dresden, Dresden, Germany
  • 20Department of Anesthesiology, Surgical Intensive Care Medicine and Pain Therapy, Vivantes Hospital Neukölln, Berlin, Germany
  • 21Institute for Clinical Chemistry, Jena University Hospital, Jena, Germany
  • 22Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
JAMA Intern Med. 2016;176(9):1266-1276. doi:10.1001/jamainternmed.2016.2514
Abstract

Importance  High-dose intravenous administration of sodium selenite has been proposed to improve outcome in sepsis by attenuating oxidative stress. Procalcitonin-guided antimicrobial therapy may hasten the diagnosis of sepsis, but effect on outcome is unclear.

Objective  To determine whether high-dose intravenous sodium selenite treatment and procalcitonin-guided anti-infectious therapy in patients with severe sepsis affect mortality.

Design, Setting, and Participants  The Placebo-Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT), a multicenter, randomized, clinical, 2 × 2 factorial trial performed in 33 intensive care units in Germany, was conducted from November 6, 2009, to June 6, 2013, including a 90-day follow-up period.

Interventions  Patients were randomly assigned to receive an initial intravenous loading dose of sodium selenite, 1000 µg, followed by a continuous intravenous infusion of sodium selenite, 1000 µg, daily until discharge from the intensive care unit, but not longer than 21 days, or placebo. Patients also were randomized to receive anti-infectious therapy guided by a procalcitonin algorithm or without procalcitonin guidance.

Main Outcomes and Measures  The primary end point was 28-day mortality. Secondary outcomes included 90-day all-cause mortality, intervention-free days, antimicrobial costs, antimicrobial-free days, and secondary infections.

Results  Of 8174 eligible patients, 1089 patients (13.3%) with severe sepsis or septic shock were included in an intention-to-treat analysis comparing sodium selenite (543 patients [49.9%]) with placebo (546 [50.1%]) and procalcitonin guidance (552 [50.7%]) vs no procalcitonin guidance (537 [49.3%]). The 28-day mortality rate was 28.3% (95% CI, 24.5%-32.3%) in the sodium selenite group and 25.5% (95% CI, 21.8%-29.4%) (P = .30) in the placebo group. There was no significant difference in 28-day mortality between patients assigned to procalcitonin guidance (25.6% [95% CI, 22.0%-29.5%]) vs no procalcitonin guidance (28.2% [95% CI, 24.4%-32.2%]) (P = .34). Procalcitonin guidance did not affect frequency of diagnostic or therapeutic procedures but did result in a 4.5% reduction of antimicrobial exposure.

Conclusions and Relevance  Neither high-dose intravenous administration of sodium selenite nor anti-infectious therapy guided by a procalcitonin algorithm was associated with an improved outcome in patients with severe sepsis. These findings do not support administration of high-dose sodium selenite in these patients; the application of a procalcitonin-guided algorithm needs further evaluation.

Trial Registration  clinicaltrials.gov Identifier: NCT00832039

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