Vitamin C in Cardiac Surgery Patients
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 21 - 79 |
| Updated: | 9/2/2018 |
| Start Date: | July 6, 2017 |
| End Date: | March 31, 2019 |
Advancing the Cardiovascular Science of Vitamin C in Cardiac Surgery Patients
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.
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.
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
We found this trial at
1
site
Wilkes-Barre, Pennsylvania 18711
Principal Investigator: Scott Bolesta, PharmD
Phone: 570-714-6642
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