Physiological, Biochemical, and Pathological Determinants of Oxidative Stress in Pediatric Sepsis Requiring Intensive Care

Abstract

Background: Oxidative stress contributes to endothelial dysfunction, mitochondrial injury, and multiple-organ failure in pediatric sepsis, but its major clinical determinants remain insufficiently defined. This study evaluated physiological, biochemical, and pathological factors associated with oxidative stress among children with sepsis requiring intensive care.

Methods: This multicentre prospective observational cohort study included 120 children aged 1 month to 15 years admitted with sepsis between January and August 2025. Clinical and laboratory variables were recorded within six hours of admission. Malondialdehyde, 8-hydroxy-2′-deoxyguanosine, total antioxidant capacity, superoxide dismutase, and reduced glutathione were measured, and a composite oxidative stress index was calculated. Multivariable regression identified independent determinants of oxidative stress and its relationship with outcomes.

Results: The cohort included 68 males and 52 females. Septic shock occurred in 54 children, acute kidney injury in 34, pediatric acute respiratory distress syndrome in 29, and mortality in 25. Children with high oxidative stress had higher lactate concentrations, vasoactive-inotropic scores, rates of septic shock, mechanical ventilation, organ dysfunction, and mortality, but lower serum albumin and antioxidant levels. Independent determinants were serum lactate, vasoactive-inotropic score, hypoalbuminemia, septic shock, acute kidney injury, and pediatric acute respiratory distress syndrome. High oxidative stress independently predicted intensive care mortality.

Conclusion: Oxidative stress in pediatric sepsis reflects the combined effects of circulatory failure, reduced antioxidant reserve, and organ injury. Early recognition of these determinants may improve biological risk stratification in critically ill children and support timely escalation of organ-supportive management in intensive care settings.