Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock.
OBJECTIVE
Sepsis is associated with an increase in reactive oxygen species and low endogenous antioxidative capacity. We postulated that high-dose supplementation of sodium-selenite would improve the outcome of patients with severe sepsis and septic shock.


METHODS
Prospective randomized, placebo-controlled, multiple-center trial.


METHODS
Eleven intensive care units in Germany.


METHODS
Patients were 249 patients with severe systemic inflammatory response syndrome, sepsis, and septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE) III score >70.


METHODS
Patients received 1000 microg of sodium-selenite as a 30-min bolus injection, followed by 14 daily continuous infusions of 1000 microg intravenously, or placebo.


RESULTS
The primary end point was 28-day mortality; secondary end points were survival time and clinical course of APACHE III and logistic organ dysfunction system scores. In addition, selenium levels in serum, whole blood, and urine as well as serum glutathione-peroxidase-3 activity were measured. From 249 patients included, 11 patients had to be excluded. The intention-to-treat analysis of the remaining 238 patients revealed a mortality rate of 50.0% in the placebo group and 39.7% in the selenium-treated group (p = .109; odds ratio, 0.66; confidence interval, 0.39-1.1). A further 49 patients had to be excluded before the final analysis because of severe violations of the study protocol. In the remaining 92 patients of the study group, the 28-day mortality rate was significantly reduced to 42.4% compared with 56.7% in 97 patients of the placebo group (p = .049, odds ratio, 0.56; confidence interval, 0.32-1.00). In predefined subgroup analyses, the mortality rate was significantly reduced in patients with septic shock with disseminated intravascular coagulation (n = 82, p = .018) as well as in the most critically ill patients with an APACHE III score > or =102 (>75% quartile, n = 54, p = .040) or in patients with more than three organ dysfunctions (n = 83, p = .039). Whole blood selenium concentrations and glutathione peroxidase-3 activity were within the upper normal range during selenium treatment, whereas they remained significantly low in the placebo group. There were no side effects observed due to high-dose sodium-selenite treatment.


CONCLUSIONS
The adjuvant treatment of patients with high-dose sodium-selenite reduces mortality rate in patients with severe sepsis or septic shock.
Angstwurm
Matthias W A
MW
Medizinische Klinik Innenstadt, Ludwig-Maximilians Universität München, Münich, Germany.
Engelmann
Lothar
L
Zimmermann
Thomas
T
Lehmann
Christian
C
Spes
Christoph H
CH
Abel
Peter
P
Strauss
Richard
R
Meier-Hellmann
Andreas
A
Insel
Rudolf
R
Radke
Joachim
J
Schüttler
Jürgen
J
Gärtner
Roland
R
D018806:APACHE; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004211:Disseminated Intravascular Coagulation / Q000209:etiology; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D005858:Germany / Q000453:epidemiology; D005979:Glutathione Peroxidase / Q000097:blood; D017052:Hospital Mortality; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology; D011446:Prospective Studies; D018805:Sepsis / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D018038:Sodium Selenite / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D015996:Survival Rate; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D016896:Treatment Outcome
C486484:GPX3 protein, human; D005979:Glutathione Peroxidase; D018038:Sodium Selenite