Does magnesium prophylaxis reduce the incidence of atrial fibrillation following coronary bypass surgery?

Interactive CardioVascular and Thoracic Surgery, Feb 2005

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.

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Does magnesium prophylaxis reduce the incidence of atrial fibrillation following coronary bypass surgery?

Anthony Rostron 0 Aliu Sanni 0 Joel Dunning 0 0 Department of Cardiothoracic Surgery, Freeman Hospital , Freeman Road, Newcastle upon Tyne NE7 7AZ, UK 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. 2005 Published by European Association for Cardio-Thoracic Surgery. All rights reserved. 1. Introduction A best evidence topic was constructed according to a structured protocol. This protocol is fully described in the ICVTS w1x. 2. Clinical scenario 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. 3. Three-part question In wpatients undergoing cardiac surgeryx is wprophylactic magnesiumx of benefit in reducing the incidence of wpostoperative atrial fibrillationx? 4. Search strategy Medline 1966September 2004 using the OVID interface. wcardiac surgery.mp OR bypass.mp OR CABG.mp OR exp coronary artery bypass OR cardiopulmonary bypass.mp OR exp cardiovascular surgical proceduresx AND wexp Magnesiumx AND wexp arrhythmia OR postoperative arrhythmia.mp OR postoperative arrhythmias.mp OR supraventricular arrhythmia.mp OR supraventricular arrhythmias.mpx. 5. Search outcome 6. Comment Twenty studies were found that investigated the use of magnesium prophylaxis in patients undergoing cardiac surgery, using a range of strategies including pre and postoperative 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 w22x 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 inci Meta-analysis of 17 PRCTs containing 2069 patients. Studies identified from Medline, Embase, CENTRAL and cross checking. Studies included were single or double blinded PRCTs with magnesium alone as a treatment arm and a placebo control arm. 200 consecutive patients having first time CABG were randomised into two groups: Grp1-6 mmol MgSO4qNaCl before and after CABG for 4 days (Ns100) Grp2-Placebo (Ns100) A. Rostron et al. / Interactive CardioVascular and Thoracic Surgery 4 (2005) 5258 Patient group Study weaknessesycomments Magnesium groups 234y1014 (23%) Control groups 312y1015 (31%) Magnesium groups 36y596 (6%) Control groups 79y599 (13%) 5 trials (648 patients) studied side-effects, but no episodes of bradycardia or hypotension found. Grp1-12y35(34%) Grp2-14y35(40%) Grp3-5y35(14%) Grp4-1y35(3%) Ventricular arrhythmias less frequent in grps 3 and 4 (P-0.05) Atrial arrhythmias less frequent but not statistically significant Grp1-18y71(26%) Grp1-5y25(20%) Grp1-2y100(2%) Grp2-21y100(21%) P-0.001 28 trials identified of which 11 failed the inclusion criteria. Quality of trial was investigated as reason for heterogeneity but no significant difference found. The reasons for heterogeneity could not be identified. No significant difference in hospital stay, MI or mortality found. They did not include Casthely w2x, Spezale w9x, Solomon w12x, as they could not extract the data, Hazelrigg w14x, Geertman w17x as they were to recent for their study and Whistbacka w19x due to no control group Subgroup analysis of hypo- vs normokalaemic patients Hypokalaemic patients experienced arrhythmias more frequently than normokalaemic (P-0.05) Exclusions: chronic AF, concomitant valve replacement and antiarrhythmic medication. Use of digoxin,B blockers and calcium antagonists were permited. Groups not aged matched. Inclusions: good LV function and without any documented arrhythmia Exclusions: past hx of AF, heart valve disease, DM, thyroid disease, COPD CRF and patients receiving antiarrhythmic drugs digoxin and B blocking agents Table 1 (Continued) 99 consecutive patients randomised into double blinded placebo controlled trial Grp1-178 mEq of Mg after CABG (Ns49) Grp2-Placebo (Ns50) 100 patients scheduled for Cardiac surgery were randomised into a double blinded placebo-controlled trial Grp1-2 g IV MgCl2 (Ns50) Grp2-Placebox Ns50 Occurrence of Ventricular dysrythmia Supravent dysrythmia Occurrence of atrial arrythmias Ventricular arrythmias Patient group Study weaknessesycomments Grp1-7y49(14%) Grp2-14y51(27%) Grp1- 8y50(16%) Grp1- 17y50(34%) GrpA-13y25(52%) GrpB-4y25(16%) GrpC-2y22(9%) GrpD-19y25(76%) GrpA-9y25(36%) GrpB-1y25(4%) Significant differences (P-0.05) were noted for groups B and C vs A and D for artial fibrillation and ventricular arrhythmias Sotalol group 11.8% (6y51) Mg group 14.8% (8y54) Sotalol and Mg 1.9% (1y52) Control group 38% (19y50) All findings significant with Sotalol and Mg versus control P-0.0001 Exclusions: previous documented arrhythmia, CRF, 2nd or 3rd degree AV block, PPM. Use of B blockers, calcium antagonists, digoxin and diuretics permitted Exclusions: chronic AF, 2nd or 3rd degree AV block, PPM, amiodarone in previous year, thyroid disease, other associated heart surgery, valvular disease, CRF, liver dysfunction Inclusion of those with past history of arrhythmias. Exclusions: endocrineymetabolic disturbance, CRF, diuretic, digitalis or specific antiarrhythmic therapy. Preop arrhythmia and those requiring other surgical procedures. 207 patients undergoing elective CABG were randomised into four groups S-80 mg/sotalol bd from posoperative day 1 (ns51) M-1.5 g od for 6 days starting at induction of anaesthesia (ns54) SqM-both treatments (ns52) Control-no treatment (ns50) Occurrence of atrial fibrillation 85 patients undergoing CABG were randomised into two groups 1-Mg2q measured and corrected (ns43) Table 1 (Continued) Patient group 167 patients undergoing CABG were randomised into two groups 1-propranolol 20 mg qds from admission to ICU analysis of combination 2-as above qMg2q 18 gy24 h started intraoperatively (ns85) 400 patients undergoing CABG randomised into 2 groups in double blind fashion. BC-Mg2q-intermittent blood cardioplegia with Mg2q 10 ml of 2 mmolyml MgSO4; BC-intermittent cardioplegia without Mg2q 147 patients undergoing CABG were randomised into 1-Mg 50 mmoly24 h after induction and for 36 h q sotalol from 1624 h postop (ns74) 2-Sotalol alone from 1624 h postop (ns73) Ventricular ectopia Occurrence of AF during postop stay and on POD1 15y25 had AF 28y25 had AF Psnot significant A. Rostron et al. / Interactive CardioVascular and Thoracic Surgery 4 (2005) 5258 Study weaknessesycomments EF-30% Creat )120 Combination therapy led to xs hypotension Conditions: EF)0.5, normal preop Mg2q, no documented arrhythmia. Conditions: )18 years old, lack of chronic arrhythmia, EF)0.25, normal renal function, normal liver function, systolic BP)90 mmHg Exclusions: redoyemergency surgery, renal or hepatic dysfunction This study acknowledged that their dose of Mg may have been too low Exclusions: EF-0.20, hx of arrhythmias, requiring bronchodilators, requiring haemodialysis 15 AVR patients included Exclusions: other cardiovascular surgery, age-30, EF-0.3, CRF, COPD, PPM, MI-30y7, Hx of atrial arrhythmias, high degree AV block. 12% of gp1 experienced serious bradyarrhythmias H40y41 L35y40 Ps0.016 115y100 216y100 Significant difference (P-0.05) only when Mg2q levels low. Table 1 (Continued) Patient group 81 patients undergoing elective CABG randomised into 2 groups H-received 4.2 g"0.7 g of Mg2q before CPB, followed by infusion 11.9"2.8 g of Mg2q until first postop morning and further 5.5"1.0 g until second postop morning (ns41) L-received Mg2q only after CPB to a total of 2.9"0.5 g on first postop morning and 1.4"0.1 g on second postop morning 200 consecutive patients undergoing elective primary CABG were randomised into two groups 13 g Mg2qy100 ml saline over 2 h preperi and at postop days 0, 1, 2, 3 2100 ml saline at same time interval Exclsuions: abnormal renal function, reoperation, emergency operation, medication to control dysrhythmia Exclusions: NYHA I, EF-0.5, age)75, known endocrine, metabolic or renal disease, patients on diuretic, digitalis or specific antiarrhythmic medication, hx of preop arrhythmias. Exclusions: Hx of AF, preop bradycardia -50, concomitant valve surgery, redo surgery, BP -100 mmHg, renal or respiratory dysfunction. B blocker administerd until 1 day before operation and not reinstituted unless necessary. 50% offpump in each group Exclusions: antiarrhythmic medication, impaired renal function. A. Rostron et al. / Interactive CardioVascular and Thoracic Surgery 4 (2005) 5258 Study weaknessesycomments Single Supraventricentre PRCT cular (level 1b) arrhythmias 111y66 (16.7%) 224y64 (37.5%) Ps0.013 dence 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. w5x 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. w10x 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 postop 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. w14x in 2004 randomized 105 patients to receive 80 mgykg of magnesium preop, then 8 mg kgy1 hy1 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. w15x performed the largest study on magnesium prophylaxis, with 400 patients randomized in a double blind fashion to receive 40 mmol of 2 mmolyml A. Rostron et al. / Interactive CardioVascular and Thoracic Surgery 4 (2005) 5258 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 mmolyl of cardioplegia, when actually they should have used a higher dose to obtain a concentration nearer 15 mmolyl of cardioplegia. Bert et al. w16x 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 Betablockers, Digoxin or controls. Kaplan et al. w20x performed a study in 200 patients, giving 3 g of Magnesium intravenously pre- and postoperatively 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. w15x who performed the largest study recommends 15 mmolyl in the cardioplegia solution although they used a dose smaller than this in their study. Toraman et al. w5x 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 mlyh) 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. 7. Clinical bottom line 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. Appendix A. ICVTS on-line discussion Author: Henrique H. Veloso (Electrophysiology Section, Hospital da Veneravel Ordem Terceira da Penitncia, Rio 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 w1x, 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 w2x and amiodarone w3x, 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.


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Anthony Rostron, Aliu Sanni, Joel Dunning. Does magnesium prophylaxis reduce the incidence of atrial fibrillation following coronary bypass surgery?, Interactive CardioVascular and Thoracic Surgery, 2005, 52-58, DOI: 10.1510/icvts.2004.100339