title: Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock: A Randomized Clinical Trial.
abstract: 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.
  
  
  
  To determine whether high-dose intravenous sodium selenite treatment and procalcitonin-guided anti-infectious therapy in patients with severe sepsis affect mortality.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  clinicaltrials.gov Identifier: NCT00832039.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany2Center for Sepsis Control & Care, Jena University Hospital, Jena, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Bloos
authors.affiliation: Clinical Trial Centre Leipzig, University of Leipzig, Leipzig, Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Trips
authors.affiliation: Department of Intensive Care Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Nierhaus
authors.affiliation: Department of Anesthesiology, University Hospital Munich, Munich, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Briegel
authors.affiliation: Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario, Canada.
authors.forename: Daren K
authors.initials: DK
authors.lastname: Heyland
authors.affiliation: Department of Anesthesiology and Surgical Intensive Care Medicine, Hospital Augsburg, Augsburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jaschinski
authors.affiliation: Department of Anesthesiology, University Hospital Göttingen, Göttingen, Germany.
authors.forename: Onnen
authors.initials: O
authors.lastname: Moerer
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Oldenburg, Oldenburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Weyland
authors.affiliation: Department of Intensive Care Medicine, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany.
authors.forename: Gernot
authors.initials: G
authors.lastname: Marx
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Greifswald, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gründling
authors.affiliation: Department of Intensive Care Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kluge
authors.affiliation: Department of Anesthesiology, University Hospital Munich, Munich, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Kaufmann
authors.affiliation: Department of Anesthesiology and Surgical Intensive Care Medicine, Hospital Augsburg, Augsburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Ott
authors.affiliation: Department of Anesthesiology, University Hospital Göttingen, Göttingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Quintel
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Oldenburg, Oldenburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Jelschen
authors.affiliation: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Meybohm
authors.affiliation: Department of Nephrology and Intensive Care Medicine, Charité Berlin, Berlin, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Rademacher
authors.affiliation: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, HELIOS Hospital Erfurt, Erfurt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meier-Hellmann
authors.affiliation: Department of General Surgery, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Utzolino
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Udo X
authors.initials: UX
authors.lastname: Kaisers
authors.affiliation: Department of Anesthesiology and Surgical Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Putensen
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Medical Center Kiel, Kiel, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Elke
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Dresden, Dresden, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Ragaller
authors.affiliation: Department of Anesthesiology, Surgical Intensive Care Medicine and Pain Therapy, Vivantes Hospital Neukölln, Berlin, Germany.
authors.forename: Herwig
authors.initials: H
authors.lastname: Gerlach
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany2Center for Sepsis Control & Care, Jena University Hospital, Jena, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Ludewig
authors.affiliation: Institute for Clinical Chemistry, Jena University Hospital, Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kiehntopf
authors.affiliation: Clinical Trial Centre Leipzig, University of Leipzig, Leipzig, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Bogatsch
authors.affiliation: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Engel
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany2Center for Sepsis Control & Care, Jena University Hospital, Jena, Germany.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Brunkhorst
authors.affiliation: Clinical Trial Centre Leipzig, University of Leipzig, Leipzig, Germany22Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany2Center for Sepsis Control & Care, Jena University Hospital, Jena, Germany.
authors.forename: Konrad
authors.initials: K
authors.lastname: Reinhart
mesh_terms: D000368:Aged; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005858:Germany / Q000453:epidemiology; D017052:Hospital Mortality; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality; D018038:Sodium Selenite / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D015415:Biomarkers; D002116:Calcitonin; D018038:Sodium Selenite