Abstract
IntroductionSepsis is associated with the generation of oxygen free radicals and (lacking) decreased selenium plasma concentrations. High doses of sodium selenite might reduce inflammation by a direct pro-oxidative effect and may increase antioxidant cell capacities by selenium incorporation into selenoenzymes. We investigated the effects of a continuous administration of high doses of selenium in septic shock patients.MethodsA prospective, multicentre, placebo-controlled, randomized, double-blind study was performed with an intention-to-treat analysis in severe septic shock patients with documented infection. Patients received, for 10 days, selenium as sodium selenite (4,000 μg on the first day, 1,000 μg/day on the nine following days) or matching placebo using continuous intravenous infusion. The primary endpoint was the time to vasopressor therapy withdrawal. The duration of mechanical ventilation, the mortality rates in the intensive care unit, at hospital discharge, and at 7, 14, 28 and 180 days and 1 year after randomization, and adverse events were recorded.ResultsSixty patients were included (placebo, n = 29; selenium, n = 31). The median time to vasopressor therapy withdrawal was 7 days in both groups (95% confidence interval = 5–8 and 6–9 in the placebo and selenium groups, respectively; log-rank, P = 0.713). The median duration of mechanical ventilation was 14 days and 19 days in the placebo and selenium groups, respectively (P = 0.762). Mortality rates did not significantly differ between groups at any time point. Rates of adverse events were similar in the two groups.ConclusionContinuous infusion of selenium as sodium selenite (4,000 μg on the first day, 1,000 μg/day on the nine following days) had no obvious toxicity but did not improve the clinical outcome in septic shock patients. Trial Registration = NCT00207844.
Highlights
Sepsis is associated with the generation of oxygen free radicals and decreased selenium plasma concentrations
Characteristics of patients at inclusion There was no significant difference between the two patient groups for the general characteristics at randomization except for the admission category, which showed a greater proportion of patients of medical origin in the selenium group (Table 1)
The majority of the patients were included within 48 hours after intensive care units (ICUs) admission, with no significant difference between groups (79% and 90% in the placebo and selenium groups, respectively; P = 0.405)
Summary
Sepsis is associated with the generation of oxygen free radicals and (lacking) decreased selenium plasma concentrations. High doses of sodium selenite might reduce inflammation by a direct pro-oxidative effect and may increase antioxidant cell capacities by selenium incorporation into selenoenzymes. We investigated the effects of a continuous administration of high doses of selenium in septic shock patients. In severe sepsis patients or in systemic inflammatory response syndrome patients, there is an early 40% decrease in plasma selenium concentrations that could be associated with a decrease of antioxidant defences [6]. Recent data suggest that selenium administration as sodium selenite could induce a dose-dependent favourable effect on the clinical outcome and survival in septic shock, especially in severe septic shock patients [3,7,8,9,10]
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