Endothelial Dysfunction and Selenium Status in Children With Acute Systemic Inflammatory Response

Endothelial Dysfunction, Regulation of Acute Inflammatory Response, Selenium Deficiency

The overall hypotheses of this project is that severe sepsis is associated with endothelial dysfunction in pediatric patients and that selenium deficiency is associated with changes in biological markers of endothelial dysfunction and that these changes, in turn, are associated with worse clinical prognosis.

Background: Oxidative stress occurs during shock as a result of granulocytes and endothelial cell activation. Higher intensity of endothelial activation is associated with unfavorable outcomes. Selenium is an essential trace element that plays a key role in the antioxidant defenses and whose plasma concentrations have been low in critically ill patients. There are no clinical studies, especially in pediatric patients that consider the roles of selenium and nutritional status in the modulation of endothelial adaptive response during the inflammatory response secondary to shock. The investigators hypothesize that selenium deficiency is associated with changes in biological markers of endothelial dysfunction and that these changes, in turn, are associated with worse clinical prognosis. Objectives: 1) to investigate the association between selenium (Se) status and the endothelial activation in children during acute systemic inflammatory response and 2) to investigate whether the intensity of endothelial activation can predict the clinical outcome in children with systemic inflammatory response. Methodology: prospective, observational study in children admitted to an intensive care unit (ICU) with systemic inflammatory response. The primary outcome will be 'intensity endothelial activation' which will be defined based on biological markers (SE-selectin, soluble intercellular molecule 1 of Vascular Cell adhesion Molecule and soluble adhesion-1). The association between the state of Se (anthropometric measurements, blood levels of selenium and erythrocyte glutathione peroxidase, selenoprotein P activity) and this outcome will be investigated in a multiple logistic model considering age, gender, primary diagnosis, prognostic scores and clinical characteristics. The secondary outcome will be 'clinical prognosis' which will be defined based on 'organ dysfunction' (creatinine level, platelets level and arterial hypotension), infectious complications during the staying in ICU and death up to 28 days. In this step the explanatory variables will be the same used in the first analyse plus to 'intensity of endothelial activation'. Participants will be followed for the duration of ICU/Hospital stay, an expected average of 28 days. Particularly, biological markers of endothelial activation will be evaluated in three different times: at baseline and on days 3 and 5 ICU. Expected results: if the study hypotheses are correct, they may justify the analysis of biomarkers of endothelial activation in medical practice and in future studies assessing the benefits of selenium supplementation in critical illness.

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