title: Perioperative intravenous acetaminophen attenuates lipid peroxidation in adults undergoing cardiopulmonary bypass: a randomized clinical trial.
abstract: BACKGROUND
  Cardiopulmonary bypass (CPB) lyses erythrocytes and induces lipid peroxidation, indicated by increasing plasma concentrations of free hemoglobin, F2-isoprostanes, and isofurans. Acetaminophen attenuates hemeprotein-mediated lipid peroxidation, reduces plasma and urine concentrations of F2-isoprostanes, and preserves kidney function in an animal model of rhabdomyolysis. Acetaminophen also attenuates plasma concentrations of isofurans in children undergoing CPB. The effect of acetaminophen on lipid peroxidation in adults has not been studied. This was a pilot study designed to test the hypothesis that acetaminophen attenuates lipid peroxidation in adults undergoing CPB and to generate data for a clinical trial aimed to reduce acute kidney injury following cardiac surgery.
  
  
  RESULTS
  In a prospective double-blind placebo-controlled clinical trial, sixty adult patients were randomized to receive intravenous acetaminophen or placebo starting prior to initiation of CPB and for every 6 hours for 4 doses. Acetaminophen concentrations measured 30 min into CPB and post-CPB were 11.9 ± 0.6 μg/mL (78.9 ± 3.9 μM) and 8.7 ± 0.3 μg/mL (57.6 ± 2.0 μM), respectively. Plasma free hemoglobin increased more than 15-fold during CPB, and haptoglobin decreased 73%, indicating hemolysis. Plasma and urinary markers of lipid peroxidation also increased during CPB but returned to baseline by the first postoperative day. Acetaminophen reduced plasma isofuran concentrations over the duration of the study (P = 0.05), and the intraoperative plasma isofuran concentrations that corresponded to peak hemolysis were attenuated in those subjects randomized to acetaminophen (P = 0.03). Perioperative acetaminophen did not affect plasma concentrations of F2-isoprostanes or urinary markers of lipid peroxidation.
  
  
  CONCLUSIONS
  Intravenous acetaminophen attenuates the increase in intraoperative plasma isofuran concentrations that occurs during CPB, while urinary markers were unaffected.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01366976.
authors.affiliation: Department of Anesthesiology, Vanderbilt University Medical School, Nashville, Tennessee, United States of America.
authors.forename: Frederic T
authors.initials: FT
authors.lastname: Billings
authors.affiliation: Department of Cardiac Surgery, Vanderbilt University Medical School, Nashville, Tennessee, United States of America.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Petracek
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee, United States of America; Department of Pharmacology, Vanderbilt University Medical School, Nashville, Tennessee, United States of America.
authors.forename: L Jackson
authors.initials: LJ
authors.lastname: Roberts
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee, United States of America; Department of Anesthesiology, Vanderbilt University Medical School, Nashville, Tennessee, United States of America.
authors.forename: Mias
authors.initials: M
authors.lastname: Pretorius
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000494:pharmacology; D000368:Aged; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011446:Prospective Studies
chemical_list: D010919:Placebos; D000082:Acetaminophen