Vitamin C in Cardiac Surgery Patients

Overview

Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery that increases the incidence of stroke, kidney injury and death. Vitamin C has been shown to decrease the incidence of POAF follow cardiac surgery, but the optimal dose has not been identified. With this project, the investigators plan to gather pharmacokinetic and dose-response data for vitamin C in the cardiac surgery population. The investigators plan to conduct a small interventional pilot study investigating the pharmacokinetics and pharmacodynamics of Vitamin C in patients undergoing coronary artery bypass graft (CABG) surgery. Patients enrolled will receive an intravenous dose of Vitamin C the day before surgery and the day after. Patients will have blood samples obtained with each dose for analysis of vitamin C concentrations and several biomarkers of oxidative stress. Analysis of samples will be performed within the Department of Pharmaceutical Sciences at Wilkes University.

The pathophysiology of post-operative atrial fibrillation (POAF) in cardiac surgery patients has not been fully elucidated, but inflammation and oxidative stress are associated with its occurrence. Increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and production of glutathione and nitrotyrosine have been found to occur in animal models of atrial fibrillation and patients who develop POAF. Similarly, malondialdehyde (MDA), a biomarker of lipid peroxidation, has also been shown to increase during cardiac surgery, and be significantly more elevated in patients who develop POAF. Cardiac surgery patients supplemented with ascorbic acid have reduced expression of NADPH oxidase and levels of MDA, glutathione and nitrotyrosine, and reduced POAF rates. Ascorbic acid supplementation has demonstrated a significant reduction in POAF in small clinical trials enrolling patients undergoing cardiac surgery. Collectively, these findings show that ascorbic acid prevents POAF in a novel way compared to recommended therapies such as beta-blockers and amiodarone, without the risk of significant side effects. However, the doses of ascorbic acid utilized in clinical trials have been found to inadequately suppress the production of inflammatory markers associated with POAF. Therefore, the maximum effect of ascorbic acid for POAF prevention may not have been realized in clinical trials published to date. These suboptimal responses may be attributable to known variances in medication pharmacokinetics in the cardiac surgery population that lead to reduced medication bioavailability, metabolism and elimination. The variation in ascorbic acid pharmacokinetics in this population is unknown. Thus, the contribution of the proposed research is expected to be determination of the pharmacokinetic profile of ascorbic acid and its concentration-response relationship with oxidative biomarkers associated with POAF in the cardiac surgery population.