Atrial Fibrillation is the most common complication following cardiac surgery with a reported incidence between 20% and 40% 12. It usually occurs between the second and fourth post-operative day. However, although this complication occurs frequently, the mechanism behind its development is less understood.

Numerous studies have identified and enumerated a variety of risk factors for the development of atrial fibrillation. These include increased age, male gender, history of atrial fibrillation, discontinuation of preoperative βeta-blocker therapy, congestive heart failure, electrolyte depletion (low potassium and magnesium), cardiopulmonary bypass, left atrial dysfunction, severity of coronary artery disease, respiratory disease, and pulmonary vein venting 1234567.

In an effort to prevent the occurrence of atrial fibrillation in the post-operative period, various treatment modalities have been implemented indicating its unclear pathophysiology. The key role of βeta blockers in prevention of atrial fibrillation is well recognised in many randomised control trials 89. Sotalol has an acceptable safety profile and is emerging as a key drug in the prevention of this complication 910. The role of magnesium supplements is less clear 11121314151617.

The present study was done to examine the beneficial role of sotalol and magnesium prophylaxis in the prevention of atrial fibrillation in routine coronary artery bypass graft (CABG) surgery.

Of the 590 patients who underwent first time isolated CABG at our institution during the study period, 28.0% developed post-operative atrial fibrillation. Of the 103 patients who received sotalol and magnesium, 13.6% developed atrial fibrillation compared to 31.0% in the other patients (p < 0.001).

We were able to successfully match 89 patients who received sotalol and magnesium to unique control patients who did not. Of these, 5 (5.6%) were 5-digit matches, 11 (12.4%) were 4-digit matches, 40 (44.9%) were 3-digit matches, 24 (27.0%) were 2-digit matches, and 9 (10.1%) were a 1-digit match. The patient and disease characteristics of the propensity-matched patients are shown in Table 1.

There was no significant difference with respect to in-hospital mortality between groups (sotalol and magnesium 1.1% versus control 4.5%; p = 0.17). The median length of hospital stay in the sotalol and magnesium group and control group were both 7 days [(25^th and 75^th percentiles: 6 to 9); p = 0.38].

The incidence of atrial fibrillation in the sotalol and magnesium group was significantly lower compared to the control group (Figure 1; p = 0.025); with an odds ratio of 0.42 (95% confidence interval: 0.19 to 0.91). The time of occurrence of atrial fibrillation was similar between the propensity-matched patients (Figure 2; p = 0.36).

A logistic regression analysis confirmed the beneficial effect of sotalol and magnesium for reducing post-operative atrial fibrillation (Table 2).

Numerous studies have identified and enumerated a variety of pre-, intra- and post-operative risk factors 1234567, with the aim of being able to change practice and reduce the occurrence of atrial fibrillation. Several treatment modalities have been investigated and have shown the effectiveness of either prophylactic amiodarone or sotalol in reducing this complication 910. A meta-analysis, by Wurdeman, concluded that compared to placebo, amiodarone and sotalol were both effective in reducing post-operative atrial fibrillation when used prohpylactically, and that both were equally as effective as each other 9. Sotalol has non-selective beta-blocking as well as class III antiarrhythmic activity. In addition, it has no interaction with the other beta blockers and so patients on pre-operative beta blockers other than Sotalol could be easily switched to Sotalol for atrial fibrillation prophylaxis. Sotalol is associated with an increase in QTc interval but reported incidence of torsades de pointes is very low. It can sometimes induce profound bradycardia and hypotension and should be avoided in low cardiac output states.

Recently, Forlani and associates 20 found that the incidence of atrial fibrillation after coronary operations was significantly reduced by the administration of combination sotalol and magnesium therapy. They showed in a randomised control trial of 207 consecutive CABG patients, that administration of sotalol alone and magnesium alone significantly reduced the incidence of atrial fibrillation, but more importantly, that when combined together, the incidence of atrial fibrillation was reduced to 1.9%.

The presence of hypomagnesemia following cardiac surgery is well described and has been shown to result in higher atrial myocardium excitability and an increased incidence of post-operative atrial fibrillation 14. The role of magnesium supplementation in reducing atrial fibrillation has been extensively studied with varying results.

Hazelrigg and colleagues 11 concluded that prophylactic magnesium supplementation does not significantly reduce atrial arrhythmias, and that the only benefit occurred on the first post-operative day. Sinilarly, Parikka 12 concluded that magnesium was not sufficient for decreasing the incidence of atrial fibrillation. In a recent randomised, double-blinded, placebo controlled trial, Geertman found that magnesium in addition to sotalol, was not more effective than sotalol alone in the prevention of tachyarrhythmias after CABG. They also found that serious bradyarrhythmias were observed in the magnesium-treated group of patients 13.

However, other reports in the literature have highlighted the potential role of magnesium for reducing arrhythmias post cardiac surgery 14151617. Toraman and colleagues 15 found that patients who received magnesium had a reported incidence of atrial fibrillation of just 2% compared to 21% in the control group. They point out that several studies that failed to show the benefit of magnesium in reducing atrial fibrillation were not well randomised with patients in the magnesium group being older and having more preoperative palpitations and arrhythmias 12. Alghamdi 16 published a systematic review and meta-analysis in 2005 which concluded that intravenous magnesium was associated with a significant reduction in the incidence of atrial fibrillation after coronary artery bypass surgery, with a relative risk of 0.64 (95% CI 0.47 to 0.87; p = 0.004). Another meta-analysis published in the same year by Miller and colleagues showed a similar result with patients receiving magnesium having an atrial fibrillation rate of 18% compared to 28% in the control group (p < 0.001) [28].

Our own study confirms that the combination of sotalol and magnesium can significantly reduce the incidence of post-operative atrial fibrillation, with an incidence of 13.5% compared to 27% in a propensity-matched cohort. But, unlike the study by Forlani 20, which had strict exclusion criteria, this study is based on routine clinical practice.

There are some limitations which need to be considered when drawing conclusions from this report. The first is that it is an observational study and therefore could have some degree of selection bias. The retrospective nature of the study cannot account for unknown variables affecting the outcomes that are not correlated strongly with the variables used in the propensity matching. Although, propensity score adjustment is no substitute for a properly designed randomised control trial, retrospective comparisons with propensity score adjustment are more versatile and may be more widely applicable to routine clinical practice 18. Perhaps one of the most important limitations is inextricable confounding caused by the sotalol and magnesium patients being performed completely by one surgeon. Even after careful application of multivariate analyses and propensity-matching, it remains difficult to distinguish between surgeon and treatment differences. However these results are highly suggestive of a role for the use of sotalol and magnesium in CABG and we are already embarking on a randomised control trial to confirm or refute the findings of this observational study.

In conclusion, the combination of sotalol and magnesium can significantly reduce the incidence of post-operative atrial fibrillation following coronary artery bypass surgery.