Clinical Trial: Acetaminophen for Oxidative Stress After Cardiopulmonary Bypass
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Does Preoperative Acetaminophen Reduce Biochemical Markers of Oxidative Stress From Cardiopulmonary Bypass?
Brief Summary: The current proposal tests the central hypothesis that acetaminophen will attenuate the oxidative stress response associated with cardiopulmonary bypass (CPB)-induced hemolysis in children undergoing cardiac surgery.
Detailed Summary:
Infants with complex congenital cardiac defects frequently undergo cardiopulmonary bypass (CBP) during surgical repair of their cardiac lesions (1). CBP exposes infants and children to endothelial damage, hyperoxia, hemolysis, and systemic inflammatory response (2-7). The systemic inflammatory response contributes to the organ dysfunction and is initiated by exposure of blood to the artificial surfaces of the extracorporeal circuit resulting in significant hemolysis and activation of complement. Hyperoxia has been shown to cause oxidative stress and the production of free radical molecules, which contributes to the morbidity of CPB. Hemolysis leads to free hemoglobin and the subsequent release of free iron in the plasma, which can catalyze redox reactions and has been shown to be another source of severe oxidant injury in children following bypass (8, 9). Additionally, the release of proinflammatory cytokines, hypothermia, hemorrhage requiring multiple transfusions, and activation of neutrophils leading to an enhancement of the respiratory burst contribute to oxidative injury and worsening inflammation (9).
Myoglobin and hemoglobin contain ferrous iron (Fe2+), which normally transports reversibly bound oxygen molecules to tissues. When muscle or red blood cells are damaged, the iron-chelating heme molecules are released into the plasma, and the ferrous iron is oxidized to the ferric (Fe3+) state. In the higher oxidation state, the ferric hemoproteins are able to reduce other molecules, notably hydrogen peroxide and lipid hydroperoxides, producing lipid peroxides and ferryl (Fe4+) hemoproteins. The ferryl hemoproteins can then enter an oxidation-reduction cycle with lipid molecules, causing further lipid peroxide production, leading to a cascade of oxidative damage to cellular membranes (10-12).
With increasing oxidative st
Sponsor: Vanderbilt University Medical Center
Current Primary Outcome: oxidative stress response as measured by F2-isoprostane [ Time Frame: 24 hours after cardiopulmonary bypass ]
Original Primary Outcome: Same as current
Current Secondary Outcome: renal function [ Time Frame: for the first 24 hrs after cardiopulmonary bypass ]
Original Secondary Outcome: renal function [ Time Frame: for the first 24 hrs after cardiopulmonary bypass ]
Information By: Vanderbilt University Medical Center
Dates:
Date Received: October 22, 2010
Date Started: July 2011
Date Completion:
Last Updated: April 19, 2017
Last Verified: April 2017