Effects of Intravenous Magnesium Sulfate on the QT Interval in Patients Receiving Ibutilide

Michael F. Caron, Pharm.D., Jeffrey Kluger, M.D., James P. Tsikouris, Pharm.D., Arnold Ritvo, M.D., James S. Kalus, Pharm.D., C. Michael White, Pharm.D.

Disclosures

Pharmacotherapy. 2003;23(3) 

In This Article

Abstract and Introduction

Study Objective: To determine the effect of intravenous magnesium sulfate on the QT and QTc intervals in patients receiving ibutilide for immediate chemical cardioversion of atrial flutter or fibrillation.
Design: Prospective, randomized, double-blind, placebo-controlled trial.
Setting: Hospital cardiology unit.
Patients: Twenty patients (mean age 72 ± 14 yrs) with atrial fibrillation (12 patients) or atrial flutter (8 patients) who were scheduled to receive ibutilide.
Intervention: After determining that the patients' baseline QTc intervals were less than 440 msec and baseline serum magnesium levels were within normal limits (mean 2.1 ± 0.29 mg/dl), the patients were randomly assigned to receive either a 10-minute infusion of magnesium sulfate 2 g in 50 ml of 0.9% sodium chloride or placebo immediately before ibutilide therapy. An additional 2 g of intravenous magnesium sulfate or placebo was given over 1 hour, 10 minutes after the first dose of ibutilide.
Measurements and Main Results: QT interval duration was measured manually in all 12 leads by using a 0.5-mm-scale precision ruler and magnifying lens. The QT interval increased 29% from baseline at 30 minutes after ibutilide therapy in the placebo group (p=0.007), but no significant change from baseline occurred in the magnesium sulfate group. The 30-minute QTc interval in the placebo group was 18% higher than the baseline value (p=0.01) but did not change significantly in the magnesium sulfate group. QTc changes from baseline were greater in the placebo group than in the magnesium sulfate group at 30 minutes (75 vs 19 msec, respectively, p=0.04). Magnesium sulfate reduced the risk of an ibutilide-induced QTc interval increase of greater than 30 msec or greater than 60 msec and reduced the risk of a QTc interval value of more than 500 msec by 65%, 60%, and 68%, respectively (p=0.07, p=0.175, and p=0.160).
Conclusions: Prophylactic administration of intravenous magnesium sulfate prevents increases in the QT and QTc interval 30 minutes after the last infusion of ibutilide.

The class III antiarrhythmic agent ibutilide is the only intravenous drug approved by the United States Food and Drug Administration for immediate restoration of sinus rhythm in patients with atrial fibrillation or flutter, with efficacy rates of up to 50% and 70%, respectively.[1,2] Unfortunately, the risk of torsades de pointes, occurring in approximately 4% of patients, has limited the widespread use of ibutilide.[3]

Increases in the electrocardiographic-corrected QT interval duration (QTc) and the dispersion of repolarization (QT dispersion) with class III agents enhance the risk of torsades de pointes.[4,5,6]

Magnesium sulfate is the drug of choice to restore normal sinus rhythm when torsades de pointes occurs, regardless of baseline serum magnesium levels.[7,8] Whether magnesium sulfate would be effective at preventing torsades de pointes from occurring when administered with class III antiarrhythmic agents is unknown. In a rabbit model, prophylactic intravenous magnesium sulfate prevented the occurrence of class III antiarrhythmic-induced torsades de pointes by 80% compared with placebo, but no changes in electrocardiographic effects were observed.[9] Hence, we sought to determine the effect of intravenous magnesium sulfate on the QTc interval and QTc dispersion in patients receiving ibutilide for immediate chemical cardioversion of atrial flutter or fibrillation.

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