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 ]

Test the hypothesis that acetaminophen attenuates the oxidative stress response, as measured by F2-isoprostanes, in children undergoing cardiopulmonary bypass. The primary outcome is the oxidative stress response as measured by F2-isoprostane


Original Primary Outcome: Same as current

Current Secondary Outcome: renal function [ Time Frame: for the first 24 hrs after cardiopulmonary bypass ]

Because free hemoglobin (hemolysis) has been associated with acute kidney injury (AKI) we will assess renal function as a secondary outcome in the immediate postoperative period. To assess renal function we will collect already available data including urine output, blood urea nitrogen, Creatinine and daily fluid ins and outs. Other potential confounders of AKI including cardiopulmonary bypass (CPB) time, daily use vasopressors and re-exploration for bleeding will be collected. In addition we will also measure urine neutrophil gelatinase-associated lipocalin (NGAL) as an early marker for AKI.


Original Secondary Outcome: renal function [ Time Frame: for the first 24 hrs after cardiopulmonary bypass ]

Because free hemoglobin (hemolysis) has been associated with acute kidney injury (AKI) we will assess renal function as a secondary outcome in the immediate postoperative period. To assess renal function we will collect already available data including urine output, BUN/Creatinine and daily fluid ins and outs. Other potential confounders of AKI including CPB time, daily use vasopressors and re-exploration for bleeding will be collected. In addition we will also measure urine NGAL as an early marker for AKI.


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