This is a further meta-analysis to evaluate the relationship between intravenous magnesium and POAF. All trials included in this analysis are double-blind, placebo-controlled, randomized clinical trials. The data can give greater power to assess the efficacy of intravenous magnesium on the prevention of atrial fibrillation after CABG. We combined the effect sizes of all seven included trials that used intravenous magnesium for preventing POAF through a fixed-effects model and found that intravenous magnesium significantly reduced the incidence of POAF by 36%. A meta-analysis of data collected before December 2003 [15
] found a cumulative RR of 0.64 (95% CI: 0.47-0.87) for the randomized controlled trials. Our findings are consistent with this previous meta-analysis.
This meta-analysis shows diversity in the dosing, timing and duration of magnesium administration. The diversity accounts for the inconsistency in the reported outcomes of the included trials as listed in Table . In three [23
] of the prospectively controlled clinical trials [11
], intravenous magnesium significantly reduced the incidence of POAF after CABG. In three trials, magnesium was dosed for at least 2 consecutive days postoperatively. Given that the onset of POAF following CABG generally occurs between 24 and 96 h postoperatively, with a peak incidence on the second postoperative day and that it is often associated with hypomagnesaemia, intravenous magnesium supplementation during this period may play a key role in the suppression of POAF.
Demographic bias owing to generating the sequence of randomization inadequately may be another reason for the discordance in the reported results of magnesium prophylaxis. The biased variable, if it happens to be a powerful predictor of POAF, would apparently have a strong influence on the outcome of the study. For example, one trial [22
] showed that prophylactic magnesium supplementation does not significantly reduce the incidence of POAF, patients in the magnesium group had a higher ratio of male gender (98% versus 86%, P
= 0.02). This characteristic, male gender has been consistently a risk factor for the development of POAF.
Up to now, various preventive methods including pharmacologic and non-pharmacologic interventions have been proposed in the preventive strategy of POAF. Current evidences from meta-analyses [27
] suggest that beta-blockers are effective and safe for most patients and advise that clinicians should not discontinue beta-blockers before cardiac surgery, unless contraindicated. Amiodarone can be safely added in patients at high risk for atrial fibrillation. In a recent meta-analysis, however, Patel et al
] found that amiodarone increases the risk of bradycardia and hypotension, particularly when administered intravenously. Meta-analyses of the clinical trials [8
] investigating the effect of prophylactic pacing have consistently suggested that single- or dual-site atrial pacing significantly reduces the incidence of POAF; however, it is limited in practical use because of its complexity. Furthermore, there are some other pharmaceuticals such as statins [32
], N-3 polyunsaturated fatty acids [34
], and anti-inflammatory agents [35
] being used to prevent POAF following CABG. However, the number of enrolled patients in these trails was small, and the pharmaceutical doses and administration times varied widely among studies. Thus, further studies are still necessary before confirmed conclusion. In a prospective, randomized, double-blind, placebo-controlled study, Cagli et al
] have concluded that low-dose amiodarone and magnesium combination is an effective, simple, well-tolerated, and possibly cost-effective regimen to prevent atrial fibrillation after CABG for high-risk patients. Perhaps appropriate combinations of these pharmacologic and non-pharmacologic interventions might be of benefit for further reducing POAF. In this meta-analysis, the patient population enrolled was quite homogeneous in its presentation. The studies included are of high quality, and all seven studies are double-blind, placebo-controlled, randomized trials having a Jadad score of ≥ 3. We combined all the studies using a fixed-effects mode and tested heterogeneity between trials with I2
(0.0%) and with P
value (0.8), indicating no heterogeneity.
Several potential limitations of this meta-analysis merit consideration. First, we accept that our meta-analysis included some clinical studies which had a modest sample size. Although we aimed to retrieve additional data from investigators, it was inevitable that some missing and unpublished data may still exist. Second, the exclusion of non-English-language studies and studies with fewer than 10 patients may lead to bias in effect size. In addition, follow-up time varied among included studies, and different total dose of intravenous magnesium was adopted in these studies. The discrepancy may explain clinical heterogeneity among studies, although no statistical heterogeneity is found.