Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study

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.

Micronutrients: do small things matter?

“…31 The systematic review and meta-analysis undertaken by our group 31 substantially builds on the initial very important review by Heyland et al 9 by including seven new trials, including the first four multi-centre randomised controlled trials in this area of research. [32][33][34][35] This updated review 31 indicates and supports previous findings 9 that micronutrient supplementation in the critically ill may be associated with a reduction in overall mortality, and specifically 28 day mortality.…”

The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities

“…Based on the correlative data just described, there has emerged an interest in the use of Se supplementation as an intervention of SIRS. Five studies conducted between 2007 and 2011 investigated the potential beneficial effects of Se supplementation (as sodium selenite) on SIRS and sepsis patient outcomes (8,72,123,169,252). Study populations in three of these studies ranged from 35 to 150 patients with initial doses of 400 to 4000 lg Se followed by daily infusions, and results showed increases in plasma Se and GPX3 levels.…”

Trace Elements in Critical Illness

“…Studies using a higher than median dose of selenium (500 -1000 mcg/day) have been associated with a trend towards significant reduction in mortality, whereas studies using a lower dose of selenium had no effect on mortality. Extremely high doses, however, may be associated with adverse effects and hence further research and dosefinding studies on pharmaco-nutrients are required [39]. In this context, a phase I, single-center, dose-escalating study involving 28 critically ill patients was recently conducted which demonstrated that intravenous selenium 500 mcg/ day added to the 300 mcg/day enteral supplement, resulted in a greater reduction in markers of oxidative stress and improved mitochondrial function with no apparent adverse effect on organ function [40].…”