Oxidative stress as a novel target in pediatric sepsis management

Abstract

Sepsis with secondary multisystem organ dysfunction syndrome is the leading cause of death in the pediatric intensive care unit. Increased reactive oxygen species may influence circulating and endothelial cells, contributing to inflammatory tissue injury and explaining the tissue hypoxia paradigm based on microvascular dysfunction. An impaired mitochondrial cellular oxygen utilization, rather than inadequate oxygen delivery, was claimed to play a more important role in the development of multisystem organ dysfunction syndrome. Anyway, it seems plausible that reactive oxygen species can mediate the pathophysiologic processes occurring in sepsis. However, the consensus guidelines for the management of patients with these conditions do not include the enhancement of antioxidant potential. Therefore, further investigation is needed to support interventions aimed to attenuate the severity of the systemic compromise by abrogating the mechanism of oxidative damage. Antioxidant supplementation currently in use lacks a mechanistic support. Specific pharmacologic targets, such as mitochondria or Nicotinamide Adenine Dinucleotide Phosphate-Oxidase (NADPH) oxidase system, need to be explored. Furthermore, the early recognition of oxidative damage in these seriously ill patients and the usefulness of oxidative stress biomarkers to define a cut point for more successful therapeutic antioxidant interventions to be instituted would offer a new strategy to improve the outcome of critically ill children.