Inhibition of Lipid Peroxidation During Cardiac Surgery

Not Applicable

Completed

Conditions: Cardiopulmonary Bypass Induced Lipid Peroxidation

Interventions: Drug: Acetaminophen

Registration Number: NCT01366976

Lead Sponsor: Vanderbilt University

Brief Summary: Acute kidney injury is a major complication of cardiac surgery requiring cardiopulmonary bypass (CPB). Hemolysis and rhabdomyolysis frequently occur during CPB. Hemolysis leads to an increase in free hemoglobin, whereas rhabdomyolysis leads to an increase in myoglobin. Free plasma hemoglobin and myoglobin have been shown to be independent predictors of the acute kidney injury that results from CPB. When these hemeproteins are released into the plasma, they undergo redox cycling, generating radical species that initiate lipid peroxidation and a cascade of oxidative damage to cellular membranes, notably in the kidney. F2-isoprostanes and isofurans are sensitive and specific markers of oxidative stress in vivo, and are increased after CPB, particularly in those patients with acute kidney injury. Acetaminophen inhibits the lipid peroxidation catalyzed by myoglobin and hemoglobin. Moreover, in an animal model of rhabdomyolysis-induced kidney injury, acetaminophen significantly attenuated the decrease in creatinine clearance compared to control. The current proposal tests the central hypothesis that acetaminophen will attenuate the lipid peroxidation associated with the hemolysis and rhabdomyolysis that occur in patients undergoing CPB. Demonstration that acetaminophen inhibits the lipid peroxidation resulting from CPB would provide a rationale for a prospective randomized trial to test the hypothesis that acetaminophen will reduce the acute kidney injury that results from CPB.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 67

Inclusion Criteria

Subjects, 18 to 80 years of age, scheduled for elective cardiac surgery requiring CPB
For female subjects, the following conditions must be met:

postmenopausal for at least 1 year, or status-post surgical sterilization, or if of childbearing potential, utilizing adequate birth control and a negative urine beta-hcg prior to drug treatment

Exclusion Criteria

Allergic reaction to ApAP (acetaminophen)
Evidence of severe hepatic impairment (history of liver cirrhosis or total bilirubin >2.0mg/dl)
Impaired renal function (serum creatinine >2.0 mg/dl)
Emergency surgery
Pregnancy
Breast-feeding
Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
History of alcohol or drug abuse
Treatment with any investigational drug in the 1 month preceding the study
Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
Inability to comply with the protocol, e.g. uncooperative attitude and unlikelihood of completing the study
History or evidence of active asthma

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Acetaminophen	-
Acetaminophen	Acetaminophen	Acetaminophen will ge given as 1g every 6 hours for 4 doses over a 24 hours study period

Primary Outcome Measures

Name	Time	Method
Plasma F2-isoprostane Concentrations	24 hours	Plasma F2-isoprostane concentrations as a measure of lipid peroxidation
Plasma Isofuran Concentrations	24 hours	Plasma isofuran concentrations as a measure of lipid peroxidation

Secondary Outcome Measures

Name	Time	Method
Urinary NGAL (Neutrophil Gelatinase-associated Lipocalin)	24 hours	Changes in urinary NGAL (neutrophil gelatinase-associated lipocalin) as marker of acute kidney injury
Serum Creatinine	72 hours	Serum creatinine measured over a 72 hour period