Inhibition of Lipid Peroxidation During Cardiac Surgery

Vanderbilt University

Status: Completed

Conditions: Cardiopulmonary Bypass Induced Lipid Peroxidation

Treatments: Drug: Acetaminophen

Study type: Interventional

Funder types: Other

Identifiers

NCT01366976

110423

Details and patient eligibility

About

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.

Enrollment: 67 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Subjects, 18 to 80 years of age, scheduled for elective cardiac surgery requiring CPB
2. 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

1. Allergic reaction to ApAP (acetaminophen)
2. Evidence of severe hepatic impairment (history of liver cirrhosis or total bilirubin >2.0mg/dl)
3. Impaired renal function (serum creatinine >2.0 mg/dl)
4. Emergency surgery
5. Pregnancy
6. Breast-feeding
7. 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
8. History of alcohol or drug abuse
9. Treatment with any investigational drug in the 1 month preceding the study
10. Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
11. Inability to comply with the protocol, e.g. uncooperative attitude and unlikelihood of completing the study
12. History or evidence of active asthma

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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67 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Treatment:

Drug: Acetaminophen

Acetaminophen

Active Comparator group

Description:

Acetaminophen will ge given as 1g every 6 hours for 4 doses over a 24 hours study period

Treatment:

Drug: Acetaminophen