Hochdosierte Selentherapie

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.

Angstwurm MW, Engelmann L, Zimmermann T, et al.                                                                                          Crit Care Med 2007; 35:118-26

Medizinische Klinik Innenstadt, Ludwig-Maximilians Universität München, München, Deutschland.

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.
DESIGN: Prospective randomized, placebo-controlled, multiple-center trial.
SETTING: Eleven intensive care units in Germany.
PATIENTS: 249 patients with severe systemic inflammatory response syndrome, sepsis and septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE)-III-score >70.
INTERVENTIONS: Patients received 1000 µg of sodium-selenite as a 30-min bolus injection, followed by 14 daily continuous infusions of 1000 µg intravenously, or placebo.
MEASUREMENTS AND MAIN 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 gluthation-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 >=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.