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.
Retrospective observational study.
A total of 391 critically ill patients with sepsis in multiple ICUs in an academic tertiary care hospital.
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).
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.
1 Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN.
2 Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN.
3 Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN.
4 Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN.
5 Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN.
* See also p. 919.
Drs. Janz, Bastarache, and Ware were involved in the study design. Dr. Janz, Dr. Peterson, Mr. Sills, Mr. Wickersham, Dr. May, and Dr. Roberts collected the data. Drs. Janz and Ware performed the statistical analysis. Dr. Janz drafted the article, and all authors participated in the revision of this article. All authors read and approved the final article.
Supported, in part, by the Vanderbilt CTSA grant UL1 RR024975-01 from NCRR/NIH, NIH HL103836, NIH HL090785, NIH GM42056, an American Heart Association Clinical Research Award, and an American Heart Association Established Investigator Award.
The authors have not disclosed any potential conflicts of interest.
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