2013 Mar – Association Between Cell-Free Hemoglobin, Acetaminophen, and Mortality in Patients With Sepsis: An Observational Study

Janz, David R.; Bastarache, Julie A.; Peterson, Josh F.; Sills, Gillian; Wickersham, Nancy; May, Addison K.; Roberts, L. Jackson II; Ware, Lorraine B.; Critical Care Medicine. 41(3):784-790, March 2013.
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 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).

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.

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