@article {Bloos917_2016,
	year = {2016},
	author = {Bloos, Frank and Trips, Evelyn and Nierhaus, Axel and Briegel, Josef and Heyland, Daren K and Jaschinski, Ulrich and Moerer, Onnen and Weyland, Andreas and Marx, Gernot and Gründling, Matthias and Kluge, Stefan and Kaufmann, Ines and Ott, Klaus and Quintel, Michael and Jelschen, Florian and Meybohm, Patrick and Rademacher, Sibylle and Meier-Hellmann, Andreas and Utzolino, Stefan and Kaisers, Udo X and Putensen, Christian and Elke, Gunnar and Ragaller, Maximilian and Gerlach, Herwig and Ludewig, Katrin and Kiehntopf, Michael and Bogatsch, Holger and Engel, Christoph and Brunkhorst, Frank M and Loeffler, Markus and Reinhart, Konrad},
	title = {Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock: A Randomized Clinical Trial},
	journal = {JAMA internal medicine},
	DOI = {10.1001/jamainternmed.2016.2514},
	ISSN = {2},
	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}
}