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JAMA Intern Med. 2016 Sep 1;176(9):1266-76. doi: 10.1001/jamainternmed.2016.2514.

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

Author information

1
Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany2Center for Sepsis Control & Care, Jena University Hospital, Jena, Germany.
2
Clinical Trial Centre Leipzig, University of Leipzig, Leipzig, Germany.
3
Department of Intensive Care Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
4
Department of Anesthesiology, University Hospital Munich, Munich, Germany.
5
Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario, Canada.
6
Department of Anesthesiology and Surgical Intensive Care Medicine, Hospital Augsburg, Augsburg, Germany.
7
Department of Anesthesiology, University Hospital Göttingen, Göttingen, Germany.
8
Department of Anesthesiology and Intensive Care Medicine, University Hospital Oldenburg, Oldenburg, Germany.
9
Department of Intensive Care Medicine, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany.
10
Department of Anesthesiology and Intensive Care Medicine, University Hospital Greifswald, Germany.
11
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt, Germany.
12
Department of Nephrology and Intensive Care Medicine, Charité Berlin, Berlin, Germany.
13
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, HELIOS Hospital Erfurt, Erfurt, Germany.
14
Department of General Surgery, University Hospital Freiburg, Freiburg, Germany.
15
Department of Anesthesiology and Intensive Care Medicine, University Hospital Leipzig, Leipzig, Germany.
16
Department of Anesthesiology and Surgical Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
17
Department of Anesthesiology and Intensive Care Medicine, University Medical Center Kiel, Kiel, Germany.
18
Department of Anesthesiology and Intensive Care Medicine, University Hospital Dresden, Dresden, Germany.
19
Department of Anesthesiology, Surgical Intensive Care Medicine and Pain Therapy, Vivantes Hospital Neukölln, Berlin, Germany.
20
Institute for Clinical Chemistry, Jena University Hospital, Jena, Germany.
21
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
22
Clinical Trial Centre Leipzig, University of Leipzig, Leipzig, Germany22Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.

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.

PMID:
27428731
DOI:
10.1001/jamainternmed.2016.2514
[Indexed for MEDLINE]

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