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Interact CardioVasc Thorac Surg 2005;4:52-58. doi:10.1510/icvts.2004.100339 © 2005 European Association of Cardio-Thoracic Surgery
Does magnesium prophylaxis reduce the incidence of atrial fibrillation following coronary bypass surgery?Department of Cardiothoracic Surgery, Freeman Hospital, Freeman Road, Newcastle upon Tyne NE7 7AZ, UK *Corresponding author. Tel.: +44 7801548122. E-mail address: joeldunning{at}doctors.org.uk (J. Dunning). Received 5 October 2004; accepted 5 October 2004
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether prophylactic magnesium reduces the incidence of atrial fibrillation post cardiac surgery. Altogether 113 papers were found using the reported search, of which 21 represented the best evidence on this topic. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses were tabulated. We conclude that prophylactic magnesium reduces the incidence of arrhythmias post cardiac surgery with a number needed to treat of only 13 to prevent an episode of supraventricular arrhythmia.
Key Words: Magnesium; Thoracic surgery; Prophylactic drug therapy; Arrhythmias; Review
A best evidence topic was constructed according to a structured protocol. This protocol is fully described in the ICVTS [1].
You are seeing a 78-year-old lady with triple vessel disease, diabetes and bronchitis, for whom you are going to perform a coronary arterial bypass tomorrow. She has been suffering with angina for the past two years but it has progressively got worse, and she is now housebound. Her left ventricular ejection fraction is 45% and she has had a small inferior infarct in the past. One of the house officers requested a serum Magnesium in the pre-operative bloods and you find that her Magnesium level is low. She is high risk for post-operative arrhythmias and although you do not usually give prophylactic magnesium you elect to do so in her case. The case goes without complication, and she is discharged in sinus rhythm 6 days later. You wonder whether everyone would benefit from prophylactic magnesium and thus resolve to search the literature.
In [patients undergoing cardiac surgery] is [prophylactic magnesium] of benefit in reducing the incidence of [post-operative atrial fibrillation]?
Medline 1966–September 2004 using the OVID interface. [cardiac surgery.mp OR bypass.mp OR CABG.mp OR exp coronary artery bypass OR cardiopulmonary bypass.mp OR exp cardiovascular surgical procedures] AND [exp Magnesium] AND [exp arrhythmia OR postoperative arrhythmia.mp OR postoperative arrhythmias.mp OR supraventricular arrhythmia.mp OR supraventricular arrhythmias.mp].
A total of 113 papers were found from which 20 single centre prospective randomised trials represented the best evidence. In addition, the Journal Club identified a highly relevant meta-analysis published on the 1st September 2004. These papers are listed in Table 1.
Twenty studies were found that investigated the use of magnesium prophylaxis in patients undergoing cardiac surgery, using a range of strategies including pre and post-operative administration, administration via cardioplegia and in combination with other anti-arrhythmics. Of note all studies were of sufficiently similar quality to justify inclusion here and thus we were unable to reduce the number of studies presented. The meta-analysis published in 2004 [22] provided an excellent summary of most of the papers presented here, although they excluded or missed six papers that we identified. They summarized data on a total of 2069 patients who were randomized to either magnesium prophylaxis or placebo treatment. They found that the incidence of AF was 31% in the control groups but only 23% in the Magnesium Groups. This gives a number needed to treat (NNT) of only 13 patients to prevent one episode of supraventricular arrhythmia. They also found a significant reduction of ventricular arrhythmias with an NNT of 14. In addition, they reported that of 648 patients where complications were assessed, no episodes of bradycardia or hypotension were recorded. Significant differences were found between all these studies, however, and no one prophylactic regime was found to be superior to another. Regimes ranged from a single dose of 5 mmol in the cardioplegia solution to 110 mmol over the course of 3 days. Thus, we elected to summarize all identified PRCTs including the ones missed by this study (Table 1) and to discuss the largest studies. There were six studies that investigated over 200 patients. Toraman et al. [5] in 2001 performed a PRCT in 200 patients, giving them either 6 mmol of Mg both pre- and post-operatively or placebo. Only two (2%) of patients receiving Mg went into AF compared to 21 (21%) in the control group. Unfortunately, patients receiving beta-blockers or digoxin were excluded. Forlani et al. [10] performed a PRCT in 2001, separating 207 patients into four groups. Patients received either Sotalol 80 mg bd or Magnesium 1.5 g orally for 6 days post-op or both or neither treatment. Only 1 of 52 patients who received both treatments went into AF compared to 19 of 50 control patients Hazelrigg et al. [14] in 2004 randomized 105 patients to receive 80 mg/kg of magnesium preop, then 8 mg kg–1 h–1 postop for 48 h, or placebo in 97 patients. Thirty-two treatment patients went into AF compared to 41 control patients, which was a non-significant trend towards benefit. However, the reduction in AF was significantly different between groups on day one. Yeatman et al. [15] performed the largest study on magnesium prophylaxis, with 400 patients randomized in a double blind fashion to receive 40 mmol of 2 mmol/ml Magnesium Sulphate in the cardioplegia solution, or controls. They found that the incidence of AF was 22% in the Magnesium group compared to 29% in controls which was non-significant, although the findings were significant in a subset analysis of urgent patients. The authors acknowledged that their dose of Magnesium only produced a concentration of 5 mmol/l of cardioplegia, when actually they should have used a higher dose to obtain a concentration nearer 15 mmol/l of cardioplegia. Bert et al. [16] performed a multi-arm study in 387 patients randomized into six groups of prophylaxis including 2 g of Magnesium pre-operatively, post-operatively and for 4 days after the operation. Unfortunately, addition of magnesium had no beneficial effect as compared to Beta-blockers, Digoxin or controls. Kaplan et al. [20] performed a study in 200 patients, giving 3 g of Magnesium intravenously pre- and post-operatively and for 3 days post-op. No significant difference was found overall, although in a subanalysis of patients who had a low pre-operative serum magnesium a significant reduction was demonstrated. In summary, prophylactic magnesium significantly reduces the incidence of arrhythmia with a number needed to treat of around 13. This may be due to the fact that hypomagnesaemia is common around the time of coronary artery bypass graft surgery and 17 out of the 20 studies measured serum magnesium levels, all agreeing that normomagnesaemia affords protection from arrhythmias. With regard to which regime should be employed, Yeatman et al. [15] who performed the largest study recommends 15 mmol/l in the cardioplegia solution although they used a dose smaller than this in their study. Toraman et al. [5] found the greatest beneficial effect in their large study of 200 patients. They used 6 mmol MgSO4 infusion in 100 ml 0.9% NaCl solution (at 25 ml/h) the day before surgery, just after cardiopulmonary bypass, and once daily for 4 days after surgery. As this study demonstrates the largest benefit in a well conducted study, perhaps this should be regarded as the optimal regime so far investigated.
Prophylactic magnesium reduces the incidence of arrhythmias post cardiac surgery with a number needed to treat of only 13 to prevent an episode of supraventricular arrhythmia.
Author: Henrique H. Veloso (Electrophysiology Section, Hospital da Venerável Ordem Terceira da Penitencia, Rio de de Janeiro, Brazil) eComment: This meta-analysis provides important information regarding the role of magnesium in preventing atrial fibrillation after coronary bypass surgery. The following step is to define the efficacy of magnesium in comparison with other traditional interventions. Analyzing the data from a previous meta-analysis [1], it is possible to observe that the numbers needed to treat (NNT) for traditional drugs used to avoid postoperative atrial fibrillation are clearly inferior to that reported for magnesium. The calculated NNTS for beta-blockers, sotalol, and amiodarone were 7, 5, and 7, respectively; while for magnesium, it was 13. However, some small studies comparing directly magnesium with other interventions, such as sotalol [2] and amiodarone [3], failed to demonstrate the difference between the therapies. In conclusion, the comparison of magnesium with traditional interventions must be performed to define if this electrolyte is a first line prophylaxis for postoperative atrial fibrillation or should be reserved for patients with contraindications for traditional therapies. References 1 Crystal E, Connolly SJ, Sleik K, Ginger TJ, Yusuf S. Interventions on prevention of postoperative atrial fibrillation in patients undergoing heart surgery: a meta-analysis. Circulation 2002 106 pp. 75–802 Forlani S, De Paulis R, de Notaris S, Nardi P, Tomai F, Proietti I, Ghini AS, Chiariello L. Combination of sotalol and magnesium prevents atrial fibrillation after coronary artery bypass grafting. Ann Thorac Surg 2002 74 pp. 720–5 3 Treggiari-Venzi MM, Waeber JL, Perneger TV, Suter PM, Adamec R, Romand JA. Intravenous amiodarone or magnesium sulphate is not cost-beneficial prophylaxis for atrial fibrillation after coronary artery bypass surgery. Br J Anaesth 2000 85 pp. 690–5
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Abstract
1. Introduction
