Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock: A Randomized Clinical Trial
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Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock: A Randomized Clinical Trial. / Bloos, Frank; Trips, Evelyn; Nierhaus, Axel; Briegel, Josef; Heyland, Daren K; Jaschinski, Ulrich; Moerer, Onnen; Weyland, Andreas; Marx, Gernot; Gründling, Matthias; Kluge, Stefan; Kaufmann, Ines; Ott, Klaus; Quintel, Michael; Jelschen, Florian; Meybohm, Patrick; Rademacher, Sibylle; Meier-Hellmann, Andreas; Utzolino, Stefan; Kaisers, Udo X; Putensen, Christian; Elke, Gunnar; Ragaller, Maximilian; Gerlach, Herwig; Ludewig, Katrin; Kiehntopf, Michael; Bogatsch, Holger; Engel, Christoph; Brunkhorst, Frank M; Loeffler, Markus; Reinhart, Konrad; SepNet Critical Care Trials Group.
in: JAMA INTERN MED, Jahrgang 176, Nr. 9, 01.09.2016, S. 1266-1276.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock: A Randomized Clinical Trial
AU - Bloos, Frank
AU - Trips, Evelyn
AU - Nierhaus, Axel
AU - Briegel, Josef
AU - Heyland, Daren K
AU - Jaschinski, Ulrich
AU - Moerer, Onnen
AU - Weyland, Andreas
AU - Marx, Gernot
AU - Gründling, Matthias
AU - Kluge, Stefan
AU - Kaufmann, Ines
AU - Ott, Klaus
AU - Quintel, Michael
AU - Jelschen, Florian
AU - Meybohm, Patrick
AU - Rademacher, Sibylle
AU - Meier-Hellmann, Andreas
AU - Utzolino, Stefan
AU - Kaisers, Udo X
AU - Putensen, Christian
AU - Elke, Gunnar
AU - Ragaller, Maximilian
AU - Gerlach, Herwig
AU - Ludewig, Katrin
AU - Kiehntopf, Michael
AU - Bogatsch, Holger
AU - Engel, Christoph
AU - Brunkhorst, Frank M
AU - Loeffler, Markus
AU - Reinhart, Konrad
AU - SepNet Critical Care Trials Group
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
U2 - 10.1001/jamainternmed.2016.2514
DO - 10.1001/jamainternmed.2016.2514
M3 - SCORING: Journal article
C2 - 27428731
VL - 176
SP - 1266
EP - 1276
JO - JAMA INTERN MED
JF - JAMA INTERN MED
SN - 2168-6106
IS - 9
ER -