Plasma antioxidant capacity as a predictor of mortality in critically ill patients

Background: Sepsis and shock are associated with high morbidity and mortality in critically ill patients. Oxidative stress contributes to endothelial dysfunction and multiorgan failure, but the prognostic value of total plasma antioxidant capacity, measured by the Ferric Reducing Antioxidant Power (FRAP) assay, has not been systematically evaluated in postoperative patients. Methods: We conducted a prospective, multicentre observational study including 464 critically ill postoperative patients admitted to intensive care units at three Spanish hospitals (2021–2026). Plasma FRAP levels were measured within the first 24 h after surgery or after clinical diagnosis of sepsis or shock, according to patient status. Clinical severity was assessed using Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. Associations between FRAP, shock, endothelial damage and 90-day mortality were analysed using survival and regression analyses. Endothelial-associated responses were evaluated in Human Umbilical Vein Endothelial Cells incubated with patient plasma. Results: FRAP levels were significantly higher in patients with shock, particularly in those with septic shock and in non-survivors (p < 0.001). FRAP positively correlated with Acute Physiology and Chronic Health Evaluation II scores and was independently associated with 90-day mortality (HR = 4.69; p < 0.05). Elevated FRAP was associated with endothelial damage and with increased FRAP levels in HUVEC supernatants. FRAP showed good discrimination for 90-day mortality (Area Under the Curve = 0.881; 95% CI: 0.775–0.987). Comparative analyses demonstrated slightly higher discriminative performance for FRAP compared with APACHE II within the present cohort, while combined FRAP-APACHE II models showed improved performance in precision-recall analyses. Conclusions: Elevated plasma Ferric Reducing Antioxidant Power levels in postoperative critically ill patients are associated with shock severity, endothelial injury and increased mortality, particularly in those with septic shock. This biomarker may serve as an early prognostic marker and a rapid, inexpensive and reproducible tool for risk stratification in critical care settings.