Abstract | OBJECTIVES: DESIGN: Single-center, randomized, double-blind, placebo-controlled phase II trial. SETTING: Medical ICU in a tertiary, academic medical center. PATIENTS: INTERVENTIONS: Patients were randomized 1:1 to enteral acetaminophen 1 g every 6 hours for 3 days (n = 18) or placebo (n = 22) with the same dosing schedule and duration. MEASUREMENTS AND MAIN RESULTS:
F2-Isoprostanes on study day 3, the primary outcome, did not differ between acetaminophen (30 pg/mL; interquartile range, 24-41) and placebo (36 pg/mL; interquartile range, 25-80; p = 0.35). However, F2-isoprostanes were significantly reduced on study day 2 in the acetaminophen group (24 pg/mL; interquartile range, 19-36) when compared with placebo (36 pg/mL; interquartile range, 23-55; p = 0.047). Creatinine on study day 3, a secondary outcome, was significantly lower in the acetaminophen group (1.0 mg/dL; interquartile range, 0.6-1.4) when compared with that in the placebo (1.3 mg/dL; interquartile range, 0.83-2.0; p = 0.039). There was no statistically significant difference in hospital mortality ( acetaminophen 5.6% vs placebo 18.2%; p = 0.355) or adverse events ( aspartate aminotransferase or alanine aminotransferase > 400; acetaminophen 9.5% vs placebo 4.3%; p = 0.599). CONCLUSIONS: In adults with severe sepsis and detectable plasma cell-free hemoglobin, treatment with acetaminophen within 24 hours of ICU admission may reduce oxidative injury and improve renal function. Additional study is needed to confirm these findings and determine the effect of acetaminophen on patient-centered outcomes.
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Authors | David R Janz, Julie A Bastarache, Todd W Rice, Gordon R Bernard, Melissa A Warren, Nancy Wickersham, Gillian Sills, John A Oates, L Jackson Roberts 2nd, Lorraine B Ware, Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis Study Group |
Journal | Critical care medicine
(Crit Care Med)
Vol. 43
Issue 3
Pg. 534-41
(Mar 2015)
ISSN: 1530-0293 [Electronic] United States |
PMID | 25474535
(Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Analgesics, Non-Narcotic
- F2-Isoprostanes
- Hemoglobins
- Acetaminophen
- Creatinine
- Propofol
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Topics |
- Acetaminophen
(administration & dosage, adverse effects, therapeutic use)
- Adult
- Analgesics, Non-Narcotic
(adverse effects, therapeutic use)
- Cell-Free System
- Creatinine
(blood)
- Critical Illness
- Double-Blind Method
- F2-Isoprostanes
(blood)
- Female
- Hemoglobins
(analysis)
- Hospital Mortality
- Humans
- Male
- Middle Aged
- Oxidation-Reduction
(drug effects)
- Propofol
(administration & dosage)
- Respiration, Artificial
- Sepsis
(drug therapy, mortality, physiopathology)
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