Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 8  |  Issue : 2  |  Page : 59-65

Ascorbic acid versus magnesium for the prevention of atrial fibrillation after coronary artery bypass grafting surgery


1 Department of Anesthesia, Faculty of Medicine, Cairo University, Cairo, Egypt
2 Department of Cardiothoracic Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt

Date of Submission17-Jan-2014
Date of Acceptance04-Mar-2014
Date of Web Publication20-Oct-2014

Correspondence Address:
Abdelhay Ebade
MD,1 Elmekawleen Elarab St. from Gesr Elsewase, Elnozha, Masr Elgidida Flat No. 5, Cairo 1135
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-9090.143259

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  Abstract 

Objective
The aim of the study was to evaluate the prophylactic use of ascorbic acid or magnesium on frequency of postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass grafting surgery with cardiopulmonary bypass.
Patients and methods
The study included 60 patients divided into three equal groups (n = 20): the control group (group C) received saline infusion, the magnesium group (group M) received 2 g magnesium sulfate after induction of anesthesia, 1 g after 12 h followed by 1 g/8 h daily until the fifth postoperative (PO) day and the ascorbic acid group (group A) received 2 g ascorbic acid after induction of anesthesia, then 1 g after 12 h followed by 1 g/8 h daily until the fifth PO day. Operative and PO data were recorded. Primary endpoint was detection of an episode of atrial fibrillation (AF) lasting more than 10 min or the requirement for urgent intervention due to AF.
Results
Sixteen (26.7%) patients developed POAF, eight (40%) patients in group C, five (25%) in group M, and three (15%) in group A, with significantly higher frequency in group C compared with group M (P1 = 0.041) and group A (P2 = 0.001) but with nonsignificantly (P3 = 0.083) higher frequency in group M compared with group A. Four patients developed POAF on the first and 12 patients on the second PO day with nonsignificant intergroup difference. The mean duration of ICU stay was significantly longer in group C compared with groups M (P1 = 0.016) and A (P2 = 0.006), with nonsignificantly (P3 = 0.480) longer duration in group M compared with group A. The mean duration of PO hospital stay was significantly longer in group C compared with groups M (P1 = 0.008) and A (P2 = 0.004), with nonsignificantly (P3 = 0.415) longer duration in group M compared with group A.
Conclusion
Prophylactic use of ascorbic acid or magnesium significantly reduced the frequency of POAF after coronary artery bypass grafting surgery and significantly reduced ICU and hospital stay.

Keywords: Ascorbic acid, magnesium, postoperative atrial fibrillation, prophylaxis


How to cite this article:
Ebade A, Taha WS, Saleh RH, Fawzy A. Ascorbic acid versus magnesium for the prevention of atrial fibrillation after coronary artery bypass grafting surgery. Egypt J Cardiothorac Anesth 2014;8:59-65

How to cite this URL:
Ebade A, Taha WS, Saleh RH, Fawzy A. Ascorbic acid versus magnesium for the prevention of atrial fibrillation after coronary artery bypass grafting surgery. Egypt J Cardiothorac Anesth [serial online] 2014 [cited 2017 Jun 24];8:59-65. Available from: http://www.ejca.eg.net/text.asp?2014/8/2/59/143259


  Introduction Top


Atrial fibrillation (AF) is still considered the most common arrhythmia occurring after cardiac surgery. It generally occurs between 24 and 96 h postoperatively, with a peak incidence on the second postoperative (PO) day. AF occurs in ∼28-33% of the patients undergoing coronary artery bypass grafting (CABG) and in 30-63% of those operated for coexisting ischemic heart and valve disease. AF is often temporary and disappears after the recovery of mechanical and metabolic functions [1],[2],[3].

Multiple studies tried to explore the pathogenic mechanism underlying the development of postoperative atrial fibrillation (POAF). Oxidative stress has been strongly involved in the underlying mechanism of AF, particularly in the arrhythmia occurring in patients undergoing cardiac surgery with extracorporeal circulation. The ischemia/reperfusion injury occurring in the myocardial tissue contributes to the development of tissue remodeling, thought to be responsible for the functional heart impairment. Consequently, structural changes due to the cardiac tissue biomolecules attack by reactive oxygen species (ROS) and/or nitrogen species could account for functional changes in ion channels, transporters, membrane conductance, cytosolic transduction signals, and other events, all associated with the occurrence of arrhythmic consequences [4].

Current evidence suggest inhibition of prominent cardiac sources of ROS, such as nicotinamide adenine dinucleotide phosphate oxidase, and targeting subcellular compartments with the highest levels of ROS may prove to be effective therapies for AF.

Another proposed mechanism for AF is that multiple reentrant circuits develop within the atria, causing rapid depolarization of the surrounding atrial tissue. Magnesium regulates cellular enzymatic and metabolic processes throughout the body. In myocardial cells, magnesium antagonizes calcium and potassium channels. In addition, electrophysiologic studies have demonstrated slowed cardiac conduction and increased cardiac refractoriness with administration of magnesium.

These actions suggest that magnesium may inhibit substrate formation and the development of reentrant circuits within the atria that are responsible for the development and propagation of AF. Magnesium has an accepted role in the management of ventricular arrhythmias; however, the role of magnesium in the treatment and prevention of atrial tachyarrhythmias is less well defined [5],[6].

Thus, the current prospective comparative study was designed to evaluate the therapeutic yield of the prophylactic use of ascorbic acid or magnesium on the frequency of POAF in patients undergoing CABG surgery.


  Patients and methods Top


After approval of the study protocol by the local ethics committee and obtaining informed patient's consent, the current study was conducted between July 2010 and December 2013. Sixty patients assigned for elective CABG surgery with cardiopulmonary bypass (CPB) were enrolled in the study.

Patients with renal or hepatic dysfunction, patients with known hypersensitivity to the studied drugs, patients with chronic obstructive pulmonary disease, patients who had preoperative AF, permanent or temporary pacemaker, patients on medication with class I and III antiarrhythmic agents or digoxin, and patients with any degree of atrioventricular block were excluded from the study.

Patients were divided into three equal groups (n = 20): the control group (group C) receiving saline infusion, the magnesium group (group M), and the ascorbic acid group (group A). Group M received 2 g magnesium sulfate after induction of anesthesia, then 1 g after 12 h followed by 1 g every 8 h daily until the fifth PO day. Group A received 2 g ascorbic acid after induction of anesthesia, then 1 g after 12 h followed by 1 g every 8 h daily until the fifth PO day.

Patients were premedicated with midazolam at a dose of 0.03-0.05 mg/kg on arrival to the operating room. Arterial cannula was inserted in the radial artery by local anesthesia; monitors were attached then anesthesia was induced by propofol 1-2 mg/kg and cisatracurium 0.15 mg/kg with fentanyl 3-5 μg/kg, followed by controlled mechanical ventilation to keep PaCO 2 between 35 and 45 mmHg. Anesthesia was maintained by sevoflurane, cisatracurium 2 μg/kg/min, and fentanyl boluses when needed.

Heparin sulfate was given at a dose of 4 mg/kg and supplemented as needed to keep the activated clotting time longer than 400 s before going on CPB. Anesthesia was maintained on CPB by propofol 3-4 mg/kg/h and systemic temperature was allowed to drift to 34°C. Blood cardioplegia was prepared from equal volumes of normal saline and blood (1 : 1) and was composed of potassium chloride 30 mEq/l, sodium bicarbonate 26 mEq/l, and lidocaine 120 mg/l. Cardioplegia was given initially at a dose of 10-15 ml/kg followed by 5 ml/kg every 20-30 min. When inotropic support was needed, dobutamine 3-5 μg/kg/min was used.

Intraoperative hemodynamic data including heart rate, systolic and diastolic blood pressure, and central venous pressure changes were determined at time of induction of anesthesia, after CPB weaning, and 2 h thereafter. The number of grafted vessels, aortic cross clamping time, CPB time, and total operative time were also recorded. PO duration of ICU stay, hospital stay, amount of chest tube drainage, and the frequency of PO events were also noted.

The primary endpoint of the current study was the detection of an episode of AF lasting longer than 10 min or the requirement for urgent intervention due to AF as profound symptoms of AF or hemodynamically unstable situations due to AF.

Statistical analysis

Obtained data were presented as mean ± SD, ranges, numbers, and ratios. Results were analyzed using the Wilcoxon ranked test for unrelated data (Z-test) and the χ2 -test. Statistical analysis was conducted using SPSS (version 15, 2006; SPSS Inc., Chicago, Illinois, USA) for Windows statistical package. P value less than 0.05 was considered statistically significant.


  Results Top


The study included 60 patients, 42 male and 18 female with a mean age of 55.1 ± 8.2 years (range 36-68 years). Mean BMI of enrolled patients was 30.3 ± 2.1 kg/m 2 . Mean ejection fraction was 48.2 ± 11.1% (range 25-65%); 11 (18.3%) patients had EF of 35% or less, 12 (20%) patients had EF in range of greater than 35-45%, 18 (30%) patients had EF in range of greater than 45-55%, and 19 (31.7%) patients had EF of greater than 55%. There was nonsignificant difference between the studied groups with respect to patients' demographics and clinical profile [Table 1].
Table 1: Demographics and clinical profile

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Hemodynamic parameters showed nonsignificant difference between the studied groups at times of evaluation throughout surgical intervention [Table 2]. Mean ischemia time was 57.9 ± 10.5 min (range 35-75 min); mean CPB time was 78.9 ± 10.8 min (range 58-100 min); and mean total operative time was 175.7 ± 16.5 min (range 145-220 min). The mean number of grafted vessels was 3.9 ± 0.8 (range 3-5 vessels). There was nonsignificant (P>0.05) difference between the studied groups with respect to operative data [Table 3].
Table 2: Hemodynamic data

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Table 3: Operative data of studied patients

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All patients passed their PO course without development of Q wave in ECG or PO fever. Eight patients required inotropic support and five patients required defibrillation for resumption of sinus rhythm with nonsignificant difference between the studied groups with respect to the need for inotropic support or defibrillation. Sixteen patients developed POAF for a frequency of 26.7%: eight (40%) patients in group C, five (25%) in group M, and three (15%) in group A. The frequency of patients who developed POAF in group C was significantly higher compared with that of group M (P1 = 0.041) and group A (P2 = 0.001), with nonsignificantly (P3 = 0.083) higher frequency in group M compared with group A [Figure 1]. Four patients developed POAF on the first PO day, two in group C and one in each of the other groups, and the remaining 12 patients developed POAF on the second PO day, six in group C, four in group M, and two in group A, with nonsignificant difference between the studied groups with respect to the timing of occurrence of POAF [Table 4].
Figure 1:

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Table 4: Postoperative data of studied patients

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The mean duration of mechanical ventilation was 2.03 ± 0.31 h (range 1.5-2.8 h) and the mean amount of chest drainage was 1185 ± 174 ml (range 900-1600 ml) with nonsignificant difference between the studied groups with respect to duration of mechanical ventilation or amount of chest drainage. The mean duration of ICU stay was significantly longer in group C compared with groups M (P1 = 0.016) and A (P2 = 0.006), with nonsignificantly (P3 = 0.480) longer duration in group M compared with group A [Figure 2]. The mean duration of PO hospital stay was significantly longer in group C compared with groups M (P1 = 0.008) and A (P2 = 0.004), with nonsignificantly (P3 = 0.415) longer duration in group M compared with group A [Table 4] and [Figure 3].
Figure 2:

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Figure 3:

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  Discussion Top


The applied therapeutic strategy significantly improved the outcome of CABG surgery manifested as significant reduction in the frequency of post-CABG AF with subsequent significant reduction in duration of ICU and hospital stays in comparison with the control group, with nonsignificant difference between groups A and M but in favor of group A. These outcomes point spotlight on the beneficial effects of the additives used for prevention of POAF with subsequent reduction in possibility of development of additional morbidities related to ICU and hospital stays and spare patients and hospital resources.

The obtained results concerning the prophylactic role of magnesium against development of POAF are in agreement with and support those previously reported by Davis et al., who conducted a search of the PubMed database to identify studies published to evaluate the role of pharmacologic strategies beyond β-blockers in the prevention of POAF and found that sufficient evidence exists to recommend the use of magnesium as monotherapy or as add-on therapy for the prevention of POAF.

In addition, Maaroos et al. [7] tried to find out how widely different prophylactic strategies for POAF are used in Scandinavian countries and found that magnesium was used by 17% of cardiac surgeons as prophylactic measure for POAF. Khalil et al. [8] reported significantly lower incidences of AF in patients undergoing lobectomy and receiving prophylactic amiodarone alone or magnesium sulfate alone compared with control patients, with no significant difference between the amiodarone (10%) and magnesium sulfate (12.5%) groups, and there were significant differences between the three groups concerning ICU and total hospital stays.

Multiple studies denied the prophylactic effect of magnesium against the development of POAF [9],[10],[11]; however, these studies depended on the revision of previous published works either as comparative or noncomparative studies and suggested that conclusion. In support of this explanation for the difference of effect of magnesium on POAF, Arsenault et al. [12] in Cochrane study concluded that prophylaxis to prevent AF after cardiac surgery with any of the studied pharmacological or nonpharmacological interventions may be favored because of its reduction in the rate of AF, decrease in the length of stay and cost of hospital treatment, and a possible decrease in the rate of stroke.

However, this review is limited by the quality of the available data and heterogeneity between the included studies, and selection of appropriate interventions may depend on the individual patient situation and should take into consideration adverse effects and the cost associated with each approach [12].

With respect to ascorbic acid prophylaxis against development of POAF, Papoulidis et al. [13] found that supplementation of vitamin C significantly reduced the incidence of AF, the hospitalization time, the ICU stay, and the time interval for the conversion of AF into sinus rhythm. Harling et al. [14] reported that vitamins C and E significantly reduced the incidence of POAF and all-cause arrhythmia compared with controls, with a significant reduction in both ICU stay and hospital stay in the antioxidant group. Rasoli et al. [15] conducted a review of the literature concerning the use of antioxidants for prophylaxis against POAF and found that four studies showed antioxidant vitamins to significantly reduce the incidence of POAF and two studies showed that prophylactic treatment with adjuvant vitamin C and β-blockers is more effective than β-blocker therapy alone.

In addition, Rebrova et al. [16] found that administration of ascorbic acid at the stage of preparation of patients to surgery and in first 24 h after operation effectively prevented development of oxidative stress and disturbances of cardiac rhythm after CABG surgery and concluded that inclusion of ascorbic acid in drug therapy of patients with ischemic heart disease could be recommended for prevention of arrhythmia during PO period. Rodrigo et al. [17] found that the reinforcement of the antioxidant system through n-3 polyunsaturated fatty acids and vitamin C and E supplementation is a safe, well tolerated, and low-cost regimen that favorably reduces the incidence of POAF, increases antioxidant potential, and attenuates oxidative stress and inflammation.

In contrast to the obtained results concerning the use of vitamin C, Bjordahl et al. [18] found that supplementation of ascorbic acid in addition to routine PO care does not reduce AF after CABG. However, such difference of effect could be attributed to the PO administration of ascorbic acid, whereas the current study used ascorbic acid as prophylaxis after induction of anesthesia and before any manipulation that could help to release ROS; thus, prophylaxis use could strengthen the antioxidant system before the insult. Thereafter, ascorbic acid was used throughout 5 days after surgery to continue the supplementing effect to the antioxidant system.

In support of the beneficial effects of prophylaxis by vitamin C, Fukushima and Yamazaki [19] reported that blood vitamin C concentration decreases after uncomplicated elective surgery with further decreases in surgical ICU patients and attributed this decline to increased demand caused by increased oxidative stress and recommended the use of much higher doses than the recommended daily allowance or doses recommended in parenteral nutrition guidelines to normalize plasma vitamin C concentration with much higher doses in surgical ICU patients.

The reported results and review of the literature allowed concluding that prophylactic use of ascorbic acid or magnesium significantly reduced the frequency of POAF after CABG surgery and significantly reduced ICU and hospital stay. However, wider scale studies are advocated for confirmation of these results, especially those concerning magnesium, and to evaluate the outcome of combined administration of both for the frequency of POAF.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
  References Top

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Filardo G, Hamilton C, Hamman B, Hebeler RF Jr, Adams J, Grayburn P. New-onset postoperative atrial fibrillation and long-term survival after aortic valve replacement surgery. Ann Thorac Surg 2010; 90:474-479.  Back to cited text no. 3
    
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Rodrigo R, Vinay J, Castillo R, Cereceda M, Asenjo R, Zamorano J, et al. Use of vitamins C and E as a prophylactic therapy to prevent postoperative atrial fibrillation. Int J Cardiol 2010; 138:221-228.  Back to cited text no. 4
    
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Sedrakyan A, Treasure T, Browne J, Krumholz H, Sharpin C, van der Meulen J. Pharmacologic prophylaxis for postoperative atrial tachyarrhythmia in general thoracic surgery: evidence from randomized clinical trials. J Thorac Cardiovasc Surg 2005; 129:997-1005.  Back to cited text no. 5
    
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Hamid M, Kamal RS, Sami SA, Atiq F, Shafquat A, Naqvi HI, Khan FH. Effect of single dose magnesium on arrhythmias in patients undergoing coronary artery bypass surgery. J Pak Med Assoc 2008; 58:22-27.  Back to cited text no. 6
    
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Maaroos M, Tuomainen R, Price J, Rubens FD, Jideus RL, Halonen J, et al. Preventive strategies for atrial fibrillation after cardiac surgery in nordic countries. Scand J Surg 2013; 102:178-181.  Back to cited text no. 7
    
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Khalil MA, Al-Agaty AE, Ali WG, Abdel Azeem MS. A comparative study between amiodarone and magnesium sulfate as antiarrhythmic agents for prophylaxis against atrial fibrillation following lobectomy. J Anesth 2013; 27:56-61.  Back to cited text no. 8
    
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De Oliveira GS Jr, Knautz JS, Sherwani S, McCarthy RJ. Systemic magnesium to reduce postoperative arrhythmias after coronary artery bypass graft surgery: a meta-analysis of randomized controlled trials. J Cardiothorac Vasc Anesth 2012; 26:643-650.  Back to cited text no. 9
    
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Carrió ML, Ventura JL, Javierre C, Rodríguez-Castro D, Farrero E, Torrado H, et al. Does post-cardiac surgery magnesium supplementation improve outcome? Magnes Res 2012; 25:159-167.  Back to cited text no. 10
    
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Cook RC, Yamashita MH, Kearns M, Ramanathan K, Gin K, Humphries KH. Prophylactic magnesium does not prevent atrial fibrillation after cardiac surgery: a meta-analysis. Ann Thorac Surg 2013; 95:533-541.  Back to cited text no. 11
    
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Arsenault KA, Yusuf AM, Crystal E, Healey JS, Morillo CA, Nair GM, Whitlock RP. Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery. Cochrane Database Syst Rev 2013; 1:CD003611.  Back to cited text no. 12
    
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Papoulidis P, Ananiadou O, Chalvatzoulis E, Ampatzidou F, Koutsogiannidis C, Karaiskos T, et al. The role of ascorbic acid in the prevention of atrial fibrillation after elective on-pump myocardial revascularization surgery: a single-center experience - a pilot study. Interact Cardiovasc Thorac Surg 2011; 12:121-124.  Back to cited text no. 13
    
14.
Harling L, Rasoli S, Vecht JA, Ashrafian H, Kourliouros A, Athanasiou T. Do antioxidant vitamins have an anti-arrhythmic effect following cardiac surgery? A meta-analysis of randomised controlled trials. Heart 2011; 97:1636-1642.  Back to cited text no. 14
    
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Rasoli S, Kourliouros A, Harling L, Athanasiou T. Does prophylactic therapy with antioxidant vitamins have an effect on atrial fibrillation following cardiac surgery? Interact Cardiovasc Thorac Surg 2011; 13:82-85.  Back to cited text no. 15
    
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Rebrova TIu, Shipulin VM, Afanas′ev SA, Vorob′eva EV, Kiýko OG. The experience of the application of ascorbinic acid as antioxidant after coronary artery surgery with use of cardiopulmonary bypass. Kardiologiia 2012; 52:73-76.  Back to cited text no. 16
    
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Rodrigo R, Korantzopoulos P, Cereceda M, Asenjo R, Zamorano J, Villalabeitia E, et al. A Randomized Controlled Trial to Prevent Postoperative Atrial Fibrillation by Antioxidant Reinforcement. J Am Coll Cardiol 2013; 62:1457-1465.  Back to cited text no. 17
    
18.
Bjordahl PM, Helmer SD, Gosnell DJ, Wemmer GE, O′Hara WW, Milfeld DJ. Perioperative supplementation with ascorbic acid does not prevent atrial fibrillation in coronary artery bypass graft patients. Am J Surg 2012; 204:862-867.  Back to cited text no. 18
    
19.
Fukushima R, Yamazaki E. Vitamin C requirement in surgical patients. Curr Opin Clin Nutr Metab Care 2010; 13:669-676.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]


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