Association Between Cell-Free Hemoglobin, Acetaminophen, and Mortality in Patients With Sepsis: An Observational Study

Objective: To determine the association of circulating cell-free hemoglobin with poor clinical outcomes in patients with sepsis and to characterize the potential protective effects of acetaminophen, an inhibitor of hemoprotein-mediated oxidation. Design: Retrospective observational study. Patients: A total of 391 critically ill patients with sepsis in multiple ICUs in an academic tertiary care hospital. Interventions: None. Measurements and Main Results: Nonsurvivors had significantly higher plasma cell-free hemoglobin concentrations (median 20 mg/dL, interquartile range 10-40) measured on enrollment compared to survivors (10 mg/dL, interquartile range 10-30, p = 0.002). After controlling for potential confounders, patients with higher cell-free hemoglobin concentrations were significantly more likely to die in the hospital (odds ratio 1.078, 95% confidence interval 1.012-1.149, p = 0.02). In addition, receiving acetaminophen in the setting of increased cell-free hemoglobin was independently associated with a protective effect against death (odds ratio 0.48, 95% confidence interval 0.25-0.91, p = 0.026) and lower plasma concentrations of the lipid peroxidation product F-2-isoprostanes (18.5 pg/mL, interquartile range 9-22.2) compared to no acetaminophen (42 pg/mL, interquartile range 29.7-86, p = 0.009). Conclusions: In critically ill patients with sepsis, elevated concentrations of circulating cell-free hemoglobin are independently associated with an increased risk of death. Acetaminophen may exert a protective effect by reducing cell-free hemoglobin-induced oxidative injury. (Crit Care Med 2013; 41:784-790)