Vitamin C in Cardiac Surgery Patients

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.

Inclusion criteria

• Patients 21 to 79 years of age admitted to Geisinger Wyoming Valley (GWV) and scheduled to undergo urgent CABG
• Planned utilization of cardiopulmonary bypass during the surgical procedure

Exclusion criteria

• Body mass index greater than 30 kg/m2
• Estimated creatinine clearance less than 30 ml/min
• History of persistent or permanent atrial fibrillation
• Condition associated with oxidative stress or inflammation (e.g. chronic rheumatic, inflammatory or neoplastic disease, recent infection, etc.)
• Currently taking corticosteroids, non-steroidal anti-inflammatory drugs or deferoxamine
• History of oxalate kidney stones
• Currently pregnant
• History of allergic reaction to ascorbic acid products
• Currently taking any herbals or supplements (not including a multivitamin or calcium)
• Enrolled in another research study