Vitamin C in Cardiac Surgery Patients
Condition: Coronary Artery Bypass Graft Surgery
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Ascorbic Acid
Intervention type(s): Drug
Intervention description(s): Ascorbic acid doses will be mixed in 100 mL normal saline and infused over 60 minutes. The postoperative dose will be given on postoperative day #1.
Other intervention name(s): Vitamin C
Intervention MeSH terms: Ascorbic Acid
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Vitamin C; Postoperative atrial fibrillation; coronary artery bypass graft; ascorbic acid