Cell-free hemoglobin can be measured in the plasma of patients with sickle cell anemia, hemodialysis, after red blood cell transfusion, and in patients with sepsis. Cell-free hemoglobin in these patient population has been associated with poor outcomes, including an association with an increased risk of death. Acetaminophen may have a protective effect in these patient populations by inhibiting hemoprotein-mediated lipid peroxidation. The purpose of the present trial is to study the effect of acetaminophen on lipid peroxidation in adults with severe sepsis and detectable cell-free hemoglobin.

The primary hypothesis is that systemic markers of oxidative stress and lipid peroxidation, as measured by F2-isoprostanes, will be significantly lower in patients with severe sepsis and detectable cell-free hemoglobin who receive acetaminophen compared to placebo. The secondary hypothesis is that patients with severe sepsis and detectable cell-free hemoglobin treated with acetaminophen will have better clinical outcomes, including decreased incidence of acute kidney injury and lower rates of hospital mortality, compared to those who receive placebo.

Inclusion Criteria:

• Males and Female >=18 years old
• Admitted to an Intensive Care Unit
• Severe Sepsis
• Detectable plasma cell-free hemoglobin

Exclusion Criteria:

• patients who received acetaminophen in the past 48 hours prior to enrollment
• intolerance or allergy to acetaminophen
• measured AST/ALT >400 U/L in the 24 hours prior to enrollment
• chronic liver disease defined by a Child-Pugh score >4
• cannot swallow or have no enteral feeding access
• patients with no detectable cell-free hemoglobin
• patients transitioned to palliative care
• pregnant patients or women of childbearing potential without a documented pregnancy test

Participants were followed for the duration of hospital stay, an average of 4 weeks