title: Association between cell-free hemoglobin, acetaminophen, and mortality in patients with sepsis: an observational study.
abstract: 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.
  
  
  METHODS
  Retrospective observational study.
  
  
  METHODS
  A total of 391 critically ill patients with sepsis in multiple ICUs in an academic tertiary care hospital.
  
  
  METHODS
  None.
  
  
  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.
authors: Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. david.janz@vanderbilt.edu
authors: David R
authors: DR
authors: Janz
authors: Julie A
authors: JA
authors: Bastarache
authors: Josh F
authors: JF
authors: Peterson
authors: Gillian
authors: G
authors: Sills
authors: Nancy
authors: N
authors: Wickersham
authors: Addison K
authors: AK
authors: May
authors: L Jackson
authors: LJ
authors: Roberts
authors: Lorraine B
authors: LB
authors: Ware
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D002474:Cell-Free System; D016001:Confidence Intervals; D028441:F2-Isoprostanes / Q000097:blood; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D018384:Oxidative Stress / Q000187:drug effects*; D036301:Qualitative Research; D012189:Retrospective Studies; D018805:Sepsis / Q000097:blood / Q000401:mortality*; D062606:Tertiary Care Centers
chemical_list: D018712:Analgesics, Non-Narcotic; D028441:F2-Isoprostanes; D006454:Hemoglobins; D000082:Acetaminophen