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

Xavier Forceville¹ , Bruno Laviolle² , Djillali Annane³ , Dominique Vitoux⁴ , Gérard Bleichner⁵ , Jean-Michel Korach⁶ , Emmanuel Cantais⁷ , Hugues Georges⁸ , Jean-Louis Soubirou⁹ , Alain Combes¹ and Eric Bellissant²

¹Service de Réanimation Polyvalente, Centre Hospitalier de Meaux, Hôpital Saint Faron, 6–8 rue Saint Fiacre, 77104 Meaux, France

²Centre d'Investigation Clinique INSERM 0203, Unité de Pharmacologie Clinique, Hôpital de Pontchaillou, CHU de Rennes et Université de Rennes 1, 2 rue Henri le Guilloux, 35033 Rennes, France

³Service de Réanimation Médicale, Hôpital Raymond Poincaré, 104 boulevard Raymond Poincaré, 92380 Garches, France

⁴Service de Biochimie A, Hôpital Saint-Louis, avenue Claude Vellefaux, 75475 Paris cedex 10, France

⁵Service de Réanimation Polyvalente, Centre Hospitalier Victor Dupouy, 69 rue du Lieut-Col Prudhon, 95107 Argenteuil cedex, France

⁶Service de Réanimation Polyvalente, Centre Hospitalier, 51 rue du Commandant Derrien, 51005 Châlons en Champagne cedex, France

⁷Hôpital d'Instruction des Armées Sainte Anne, boulevard Sainte Anne, 83800 Toulon Naval, France

⁸Centre Hospitalier Gustave Dron, 135 rue du Président Coty, 59200 Tourcoing, France

⁹Hôpital d'Instruction des Armées Desgenettes, 108 boulevard Pinel, 69003 Lyon, France

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Critical Care 2007, 11:R73doi:10.1186/cc5960


Published:	6 July 2007

See related commentary by Heyland, http://ccforum.com/content/11/4/153

Abstract

Introduction

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.

Methods

A 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.

Results

Sixty 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.

Conclusion

Continuous 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.