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Amiodarone is considered a first-choice antiarrhythmic drug in critically ill patients with new-onset atrial fibrillation (AF). However, evidence supporting the use of this potentially toxic drug in critically ill patients is scarce. Magnesium sulphate (MgSO4) has shown to be effective for both rate and rhythm control, to act synergistically with antiarrhythmic drugs, and to prevent proarrhythmia. Treatment with MgSO4may reduce the need for antiarrhythmic drugs such as amiodarone in critically ill patients with new-onset atrial fibrillation. The efficacy of a new institutional protocol was evaluated. Patients were treated with a new institutional protocol for new-onset atrial fibrillation in critically ill patients. An MgSO4bolus (0.037 g/kg body weight in 15 minutes) was followed by continuous infusion (0.025 g/kg body weight/h). Intravenous amiodarone (loading dose 300 mg, followed by continuous infusion of 1200 mg/24 h) was given to those not responding to MgSO4within 1 hour. Clinical response was defined as conversion to sinus rhythm or decrease in heart rate <110 beats/min. Sixteen of the 29 patients responded to MgSO4monotherapy, whereas the addition of amiodarone was needed in 13 patients. Median (range) time until conversion to sinus rhythm after MgSO4was 2 (1–45) hours. Median (range) conversion time in patients requiring amiodarone was 4 (2–78) hours, and median (range) conversion time in all patients was 3 (1–78) hours. The 24-hour conversion rate was 90%. Relapse atrial fibrillation was seen in 7 patients. The magnesium-amiodarone step-up scheme reduces the need for amiodarone, effectively converts new-onset atrial fibrillation into a sinus rhythm within 24 hours, and seems to be safe in critically ill patients.