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

Methods

Between April 2000 and March 2002, we conducted a prospective, randomized, double-blind, placebo-controlled trial at Hartford Hospital. Patients were enrolled with the approval of the institutional review board at Hartford Hospital, and written informed consent was obtained. Patients older than 17 years who had atrial fibrillation or flutter and were scheduled to receive ibutilide (Corvert; Pharmacia Corp., Kalamazoo, MI) were eligible for inclusion. Patients were excluded if they had any known magnesium sulfate hypersensitivity, had received magnesium supplementation within 48 hours before the study, had moderate-to-severe renal dysfunction (serum creatinine level > 1.5 mg/dl), or were pregnant or planning to become pregnant. Also, as part of Hartford Hospital's ibutilide treatment protocol, ibutilide was not administered to patients who were receiving other drugs with the potential to prolong the QT interval, including other antiarrhythmics. The protocol also required that the baseline QTc interval be less than 440 msec and that baseline serum magnesium and potassium levels be within normal limits.

Patients received either an intravenous infusion of magnesium sulfate 2 g in 50 ml of 0.9% sodium chloride or matching placebo (50 ml of 0.9% sodium chloride alone) over the 10 minutes immediately before starting ibutilide therapy. Intravenous ibutilide 1 mg or 0.01 mg/kg for body weight less than 60 kg was given over 10 minutes, with a second 10-minute infusion of ibutilide (1 mg, or 0.01 mg/kg for body weight < 60 kg) administered to patients who did not convert to sinus rhythm within 10 minutes after the first infusion. An additional 2 g of intravenous magnesium sulfate or placebo was administered over 1 hour, 10 minutes after the first dose of ibutilide, irrespective of a second dose of ibutilide.

Twelve-lead electrocardiograms were recorded at 25 mm/sec at rest before the start of treatment and 30 and 60 minutes after completion of the final ibutilide dose. The three 12-lead electro-cardiograms for each patient were grouped together and read by a blinded study investigator. The QRS, QT, and R-R intervals were determined from lead II of the 12-lead electrocardiogram. A precision ruler method of 0.5-mm scale (Schlaedler-Quinzel, Inc., Parsippany, NJ) was used to measure all intervals because it was shown to be superior to the caliper and computer methods.[10,11]

The QT intervals were measured from the onset of the Q wave (or R wave if there was no Q wave) to the end of the T wave where it merges with the isoelectric baseline. The beginning and end of the QRS complex were determined by visual inspection, whereas the end of the T wave was obtained by extrapolating the descending slope of the T wave to the isoelectric baseline. When a U wave interrupted the down-sloping of the T wave, the visible portion of the T wave was extrapolated to the T-P baseline to define the end of the T wave. The R-R interval was measured from the peak of one R wave to the peak of an adjacent R wave. The QTc interval was corrected for heart rate by using the following formula: QTc = QT/ R-R.[12] Because the patient population was either in atrial fibrillation or atrial flutter, we measured all the QT and R-R intervals in each evaluable lead and averaged them for a more accurate assessment. The maximum and minimum QT, R-R, and QTc interval dispersions were calculated by subtracting the shortest interval from the longest interval. Heart rate was calculated by dividing 60 seconds by the lead II R-R interval (in sec).[13]

All continuous data are reported as the mean ± SD. Intergroup electrocardiographic parameter changes were compared by using the Mann-Whitney U test. Intragroup electrocardiographic parameters were compared by using analysis of variance with post hoc Bonferroni-corrected t tests. A 2 analysis was used for categorical data. A p value less than 0.05 was considered to indicate a statistically significant difference.

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