• David R Janz, Julie A Bastarache, Josh F Peterson, Gillian Sills, Nancy Wickersham, Addison K May, L Jackson Roberts, and Lorraine B Ware.
• Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. david.janz@vanderbilt.edu
• Crit. Care Med.. 2013 Mar 1;41(3):784-90.

ObjectiveTo 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.DesignRetrospective observational study.PatientsA total of 391 critically ill patients with sepsis in multiple ICUs in an academic tertiary care hospital.InterventionsNone.Measurements And Main ResultsNonsurvivors had significantly higher plasma cell-free hemoglobin concentrations (median 20mg/dL, interquartile range 10-40) measured on enrollment compared to survivors (10mg/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 F2-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).ConclusionsIn 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.

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