Sadeghpour A, Alizadehasl A, Kyavar M, et al. Impact of vitamin C supplementation on post-cardiac surgery ICU and hospital length of stay. Anesth Pain Med. 2015;5(1):e25337.
Randomized, double-blind, placebo-controlled prospective trial
The intervention group consisted of 113 participants (80 men, 33 women). The placebo group had 177 participants (111 men, 66 women). Both groups were scheduled for various cardiac surgeries. Mean age of participants was 55.78 years +13.72 years.
Vitamin C (as ascorbic acid) or placebo: The intervention group received 2 g intravenous vitamin C immediately before surgery and 1 g daily for 4 days after surgery. The placebo ampoule and tablets were matched in shape and size to the vitamin C provided.
Outcome parameters that may influence complication rates and/or recovery from cardiac surgery were chosen. These parameters included time spent in the intensive care unit (ICU) postsurgery, overall time spent in the hospital, duration of intubation after surgery, drainage volume in the ICU as well as the first 24 hours postsurgery, and incidence of atrial fibrillation postsurgery.
While time spent in the ICU was not different between groups, overall hospital stay did vary significantly. The intervention group stayed approximately 2 fewer days in the hospital than the placebo group (10.17+4.63 d vs 12+4.51 d; P=0.01). The intervention group also had a shorter intubation time (11.83+3.91 h vs 14.14+9.52 h; P=0.003). Volume of drainage in the ICU was less in the intervention group vs placebo as well (499.55 cc+296.69 cc vs 577.96 cc+454.44 cc). Incidence of postsurgical atrial fibrillation was 35.5% in the vitamin C group vs 55.9% in the placebo group (P=0.001). Perhaps most impressive, there was a statistically significant difference in postoperative complications, defined as “death, any infection and any impairment in the renal function” (P=0.042).
This study is a straightforward example of an inexpensive, natural intervention having a profound effect on outcomes. The effect of a cumulative dose of 6 g vitamin C over the course of 5 days seems remarkable. From a practical perspective, the low cost, limited amount of effort (4 tab over 4 d), and negligible downside risk should give the use of oral vitamin C widespread appeal.
This is not the first trial suggesting vitamin C may improve outcomes of cardiac surgeries. Several trials have specifically looked at atrial fibrillation and found benefit with moderate oral doses of vitamin C.
Given the current state of the evidence, vitamin C should be given to all patients having cardiac procedures, particularly coronary artery bypass surgery.
In 2007, Esami and colleagues reported dramatic improvement with the use of 2 g orally the night before coronary bypass surgery, then 1 g twice daily for 5 days after surgery.1 Fifty patients were in the intervention group and 50 in the control group. All patients were on beta blockers and wore Holter monitors for 4 days postprocedure. The incidence of atrial fibrillation was 4% in the ascorbic acid group and 26% in the control group (odds ratio [OR]:0.119; 95% confidence interval [CI]:0.025-0.558; P=0.002).
In 2014, a systematic review of 23 studies on antioxidant supplementation and cardiac surgery outcomes found that vitamin C supplementation was associated with a 50% reduction in postsurgical atrial fibrillation (OR:0.50; 95% CI:0.27-0.91; P=0.02).2 It was also associated with shorter hospital stays (standard mean deviation: −0.325; 95% CI:−0.50 to −0.14; P<0.01). As an aside, other antioxidant supplements found to impact outcomes were n-acetyl-cysteine and poly-unsaturated fatty acids, both of which lessened atrial fibrillation after surgery, albeit to a lesser extent than vitamin C.
Exactly how vitamin C improves outcomes is still being investigated. Atrial fibrillation, in particular, appears to be a multifactorial process that involves both oxidative stress and inflammatory reactants.3 The authors of the trial reviewed here speculate that these are the mechanisms most likely behind vitamin C’s postsurgical benefit.
While the study under review used a limited duration of vitamin C supplementation, there may be good reason to continue its use beyond the immediate postsurgical hospital stay. For the extended postsurgical period, healing of the surgical wound itself should be considered. Ascorbic acid is well proven to increase collagen synthesis.4,5 Longer term, vitamin C is integral to the health of the endothelium, a topic that was previously covered by Daniel Chong, ND, in the special cardiology issue of Natural Medicine Journal.6
A limitation of this study is that the status of circulating vitamin C was not measured. Whether there is an underlying deficiency of vitamin C that is being corrected with supplementation or whether doses of vitamin C higher than physiological repletion are therapeutic cannot be inferred. However, the preponderance of evidence in the systematic review of 23 studies mentioned above implies there is more than merely repletion at work.
Given the current state of the evidence, vitamin C should be given to all patients having cardiac procedures, particularly coronary artery bypass surgery. Given the simplicity and cost-effectiveness, it is a wonder that it is not yet part of standard of care.
- Eslami M, Badkoubeh RS, Mousavi M, et al. Oral ascorbic acid in combination with beta-blockers is more effective than beta-blockers alone in the prevention of atrial fibrillation after coronary artery bypass grafting. Texas Heart Inst J. 2007;34(3): 268-274.
- Ali-Hassan-Sayegh S, Mirhosseini SJ, Rezaeisadrabadi M, et al. Antioxidant supplementations for prevention of atrial fibrillation after cardiac surgery: an updated comprehensive systematic review and meta-analysis of 23 randomized controlled trials. Interact Cardiovasc Thorac Surg. 2014;18(5):646-654.
- Elahi MM, Flatman S, Matata BM. Tracing the origins of postoperative atrial fibrillation: the concept of oxidative stress-mediated myocardial injury phenomenon. Eur J Cardiovasc Prev Rehabil. 2008;15(6):735-741.
- van Robertson WB, Schwartz B. Ascorbic acid and the formation of collagen. J Biol Chem. 1953;201(2):689-696.
- Tajima S, Pinnell SR. Regulation of collagen synthesis by ascorbic acid. Ascorbic acid increases type I procollagen mRNA. Biochem Biophys Res Commun. 1982;106(2):632-637.
- Chong D. The impact of vitamin C on endothelial function. Nat Med J. 2015;7(2S). http://naturalmedicinejournal.com/journal/2015-02/impact-vitamin-c-endothelial-function.