Selenium and intensive care medicine. Clinical trials in SIRS and sepsis

Selenium is an essential component of the intracellular antioxidant system as a structural component of the active center of the glutathione peroxidas e enzymes. These selenoenzymes play a major role in protecting cells agains t peroxidation, especially lipid peroxidation and selenium seems to play a direct role in the regulation of inflammatory processes. In conditions of s ystemic inflammatory response or sepsis, patients are exposed to severe oxi dative stress. These patients already have both, a decreased plasma seleniu m and glutathion peroxidase activity at admission to the ICU as has been sh own in several studies. The degree of selenium deficiency is correlated wit h the severity of disease and the incidence of mortality. The reason for th e low plasma selenium levels is unknown. Especially it would be of interest a) if the low plasma selenium is the consequence of the systemic inflammat ory response with distribution of selenium in other compartments of the bod y, b) most important, whether the substitution of selenium might improve th e outcome and decrease the mortality rate of these patients. In 2 independently performed intention-to-treat studies including patients with systemic inflammatory response syndrome or sepsis a beneficial effect of selenium supplementation on multiple organ function and outcome could al ready be demonstrated as well as a tendency of an improved mortality rate. A prospective analytical study clearly could demonstrate the inverse relati onship between low plasma selenium and morbidity and mortality of patients with SIRS/sepsis. The results of these studies are so convincing, that we propose a randomize d, prospective, double blind multicenter phase-III study including patients with systemic inflammatory response syndrome or sepsis to investigate, whe ther a high-dose selenium substitution in addition to the recommended treat ment strategies for patients with sepsis improves outcome and mortality rat e of these patients.