Delayed increase of plasma selenoproteins and absence of side effect induced by infusion of pharmacological dose of sodium selenite in septic shock: Secondary analysis of a multicenter, randomized controlled trial - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Journal of Trace Elements in Medicine and Biology Année : 2022

Delayed increase of plasma selenoproteins and absence of side effect induced by infusion of pharmacological dose of sodium selenite in septic shock: Secondary analysis of a multicenter, randomized controlled trial

Résumé

Background: In sepsis, neutrophil respiratory bursts participate in endothelium damage, the first step to multiple organ failure. In plasma two antioxidant selenoenzymes, which protect the endothelium, decrease: selenoprotein-P, and to a lesser extent glutathione peroxidase (GPX3). Sodium selenite (Na2SeO3) is a Se donor, but also an oxidant chemotherapy drug depending on its concentration. In a previous published study, Na(2)SeO(3 )continuous infusion in septic shock patients at a pharmacological dose of 4 mg1 Se/day on day-1, followed by a high nutritional dose of 1 mg Se/day during 9 days, showed no beneficial effect on weaning of catecholamine nor on survival. In this ancillary study, we report clinical and biological effects of such continuous infusion of Na2SeO3. Methods: This was a multicenter, placebo-controlled, double-blind study on 60 patients. Na(2)SeO(3)or placebo in continuous infusion as described above. Evolution with time of plasma Se, selenoprotein-P, GPX(3), Organ dysfunction (sequential organ failure assessment SOFA scores, including PaO2/FiO(2), for respiratory failure, and plasma lactate) and quality of life at 6 months (by SF36 scores) were analyzed using two-way (time, treatment) non-parametric repeated-measures analysis of variance (Friedman test). Main Results: At baseline, plasma Se was about a quarter of reference values. From baseline to day-4 plasma Se, selenoprotein-P and GPX(3) significantly increased by 3.9, 2.7 and 1.8 respectively in the Na(2)SeO(3 )group as compared with placebo and remained elevated by 2.3, 2.7 and 2.1 at day-14 respectively (p < 0.001). Na(2)SeO(3 )did not affect global and organ by organ SOFA Scores and plasma lactate concentration at day-1 and later up to day-14. The evolution of PaO2/FiO(2) until day-14 was similar in the two groups. Quality of life in the surviving patients at 6 months was similar between the two groups. Conclusion: Continuous infusion of Na(2)SeO(3 )at 4 mg Se at day-1 seems to have neither beneficial nor toxic effect at day-1 or later and induces a late increase of selenoprotein-P at day-4. Preclinical studies are required to confirm the use of Na(2)SeO(3 )as a cytotoxic drug against neutrophils and protection of the endothelium by sele-noprotein-P.
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hal-03770365 , version 1 (15-09-2022)

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Xavier Forceville, Bruno Laviolle, Jolanta Gromadzinska, Anne Boutten, Pierre van Antwerpen, et al.. Delayed increase of plasma selenoproteins and absence of side effect induced by infusion of pharmacological dose of sodium selenite in septic shock: Secondary analysis of a multicenter, randomized controlled trial. Journal of Trace Elements in Medicine and Biology, 2022, 73, pp.127031. ⟨10.1016/j.jtemb.2022.127031⟩. ⟨hal-03770365⟩
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