Journal of the American College of Nutrition, Vol. 23, No. 5, 497S-500S (2004)
Published by the American College of Nutrition
Optimal Administration Dosage of Magnesium Sulfate for Torsades de Pointes in Children with Long QT Syndrome
Kenji Hoshino, MD,
Kiyoshi Ogawa, MD,
Takashi Hishitani, MD,
Takeshi Isobe, MD and
Yoshikatsu Eto, MD
Department of Pediatric Cardiology, Saitama Children’s Medical Center, Iwatsuki City, Saitama (K.H., K.O., T.H.), JAPAN
Department of Pediatrics, Ibaraki Children’s Hospital, Mito City, Ibaraki (T.I.), JAPAN
Department of Pediatrics, Jikei University School of Medicine, Tokyo (Y.E.), JAPAN
Address reprint requests to: Kenji Hoshino, MD, Pediatric Cardiology, Saitama Children’s Medical Center, 2100 Magome, Iwatsuki City, Saitama 339-8551, JAPAN. E-mail: a0182608{at}pref.saitama.jp
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ABSTRACT
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Background: Intravenous administration of magnesium sulphate (MgSO4) is a very effective and safe treatment for torsades de pointes (TdP) associated with acquired long QT syndrome (LQTS) in adults. Discussed here is the efficacy of MgSO4 for TdP in children with congenital and acquired LQTS.
Methods: The optimal MgSO4 dosage and serum magnesium (SMg) was determined in six consecutive children with TdP; four had congenital LQTS and two had acquired LQTS. A bolus injection of MgSO4 was given intravenously over 1 to 2 minutes followed by continuous infusion for the next 2 to 7 days.
Results: Of the six patients, five responded completely to the initial bolus of 6.1 ± 4.2 mg/kg (range, 2.3–12 mg/kg). One (a neonate with congenital LQTS) required a total of 30 mg/kg until complete TdP elimination. Continuous infusion was given at rates of 0.3 to 1.0 mg/kg/hr with no recurrence of TdP. SMg concentration was 3.9 ± 1.0 mg/dL (2.9–5.4 mg/dL) immediately after bolus injection.
Conclusion: Intravenous MgSO4 infusion effectively treated TdP in children with LQTS. Optimal bolus dosage, infusion rates and SMg concentration were 3 to 12 mg/kg, 0.5 to 1.0 mg/kg/hr and 3 to 5 mg/dL, respectively.
Key words: magnesium, torsades de pointes, long QT syndrome, children
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INTRODUCTION
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Torsades de pointes (TdP) is a serious ventricular tachycardia (VT) with a twisting QRS axis and polymorphous appearance that is associated with marked QT prolongation. The episodes usually terminate spontaneously within a few seconds, but they tend to recur and deteriorate into a uniform VT or fibrillation.
Intravenous administration of magnesium sulphate (MgSO4) was found to be a very effective and safe treatment for TdP associated with acquired long QT syndrome (LQTS) in adults [1], but in children, the efficacy of MgSO4 for TdP is still controversial.
In 1990 we first reported a dramatic effect of MgSO4 as a treatment for TdP associated with congenital LQTS in children [2]. In this study, we discuss the efficacy of MgSO4 as a treatment for TdP associated with both congenital and acquired LQTS in children. We also discuss the optimal administration dosage and extracellular concentration of magnesium (Mg) during MgSO4 therapy.
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METHODS
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Patients
We studied six consecutive paediatric patients presenting to our hospital and undergoing MgSO4 therapy for TdP associated with LQTS (Table 1). All patients were males with a mean age of 64 ± 50 months (range, 0 to 109 months) at initial presentation. The mean QT interval was 509 ± 77 ms (range, 428 to 604 ms) and the mean corrected QT (QTc) interval was 582 ± 51 ms (range, 518 to 652 ms) at initial presentation.
The diagnosis included congenital LQTS (patients 1 through 4) and acquired LQTS (patients 5 and 6). Patient 5 received patch closure of ventricular septal defect at 11 months old, and was associated with 2:1 atrioventricular block from 8 years old, which was presumed to be the cause of TdP. Patient 6 received oral disopyramide (10 mg/kg/day) for premature ventricular contraction (PVC) for 2 weeks, which was the cause of TdP.
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METHODS
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Of the six patients, one (patient 1) received other modes of therapy before administration of MgSO4, but these were not effective. The remaining five (patients 2 through 6) were given MgSO4 only for treatment of TdP. In all six patients, a bolus of MgSO4 was given intravenously until the TdP was completely abolished or the maximum total bolus dosage was reached (12 mg/kg of Mg in our centre) over 1 to 2 minutes (Table 2).
A patient who did not respond completely to the first bolus was given a second or third bolus within the 5 to 15 minute interval. In all patients, continuous infusion of MgSO4 was given over the next 2 to 7 days depending on each patient’s response to the initial bolus and Mg concentration immediately after the bolus injection. The concentration of MgSO4 solution used in this study was 1 mEq/mL, containing 12 mg of Mg/mL solution.
We also examined the efficacy of MgSO4 for TdP and discussed the optimal administration dosage (bolus injection and continuous infusion). We also examined the serum total Mg (SMg) concentrations and QTc intervals before and after administration of MgSO4. SMg concentration before administration was measured with the peripheral venous blood samples drawn from the median cubital vein just before the bolus injection. Mg concentration after administration of MgSO4 was measured in the same way immediately after the bolus injection. The concentration of SMg was measured by enzyme assay using TBA-30R Autoanalyzer (TOSHIBA Medical). The normal range in our laboratory is 1.7–2.4 mg/dL. The dosages and rates used in this study were expressed with the amount of Mg (not with MgSO4). QT interval was measured in lead II or V5, and the observed QT interval was corrected for the heart rate (QTc) according to Bazett’s formula [3].
Statistical Analysis
All data were presented as the mean ± standard deviation, and probability (p) value less than 0.05 was regarded as statistically significant. The mean levels of SMg, QT and QTc before and after administration of MgSO4 were assessed using paired t test.
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RESULTS
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Of the six patients, five (except patient 3) responded completely to the initial treatment with a single bolus and the bolus injection dosage was 6.1 ± 4.2 mg/kg (range, 2.3
12 mg/kg) in these five patients. In patient 3, frequent occurrence of TdP was almost abolished after the first bolus, but short bursts (less than 10 beats) of TdP were still recognized. Thus, the second and third bolus was given that completely abolished the TdP, and the total bolus dosage was 30 mg/kg.
A continuous infusion of MgSO4 was given preventively to all six patients at rates of 0.31.0 mg/kg/hr after the initial bolus injections. Three patients (patients 3, 4 and 5) were given higher rates compared with the other 3 patients because they showed isolated PVC after the initial bolus injection. Intravenous infusion was continued for 48 hrs and over after the complete termination of TdP (2 to 7 days).
Only one (patient 1) showed a very low SMg concentration (1.3 mg/dL) before bolus injection. In the other five, the mean SMg concentration before bolus injection was 2.1 ± 0.2 mg/dl (range, 1.82.3 mg/dL) and was within normal limits. The mean SMg concentration immediately after the bolus injection was 3.9 ± 1.0 mg/dL (range, 2.95.4 mg/dL) in 5 patients (the data of patient 4 was excluded because it was measured 24 hours after the bolus injection).
The mean QTc interval before bolus injection was 612 ± 54 millisecond (range, 518669 millisecond), which was not significantly different with that immediately after bolus injection (632 ± 35 millisecond; range, 598680 millisecond).
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DISCUSSION
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Mechanisms of Mg for TdP
It is probable that early after depolarizations (EADs) are associated with TdP. Recently, triggered activity (TA) consequent to EADs has been proposed as a cause of TdP [4,5]. According to our experiences and previous reports [1], it is observed that Mg abolishes TdP without shortening the QT interval. Kaseda et al. reported that Mg suppressed depolarization-induced automaticity when action potential duration was fixed [6]. This suggests that Mg is capable of abolishing triggered activity by inhibiting EADs directly rather than by shortening action potential duration or by suppressing the causes of EADs.
The Optimal Dosage of Mg
Administration dosages of Mg for TdP and other tachyarrhythmias have been reported in adults [1,7]. In most reports in adults, an initial bolus of 2g of MgSO4 (containing 193 mg of Mg) was given intravenously for 1 to 2 minutes and the patients who did not respond completely to the first bolus received a second bolus within 5 to 15 minutes.
In our experience, an initial bolus of 2.3 to 9 mg/kg (mean: 4.7 mg/kg) of Mg was effective except in two neonates with congenital LQTS. These two neonates needed 12 and 30 mg/kg of Mg, therefore it is recommended that bolus injection is given at 3 to 9 mg/kg initially and can be up to 12 mg/kg over 1 to 2 minutes until the TdP is completely abolished; however, if the patient does not respond completely, a second bolus can be given under the same protocol within 5 to 15 minutes.
We have found that Mg concentration continues to increase when Mg infusion is continued at a rate of 1 mg/kg/hr and above, while it decreases when infusion rate is below 0.5 mg/kg/hr. It may be preferable to give continuous infusion at a rate of 0.5 to 1.0 mg/kg/hr depending on each patient’s response to the initial bolus and also on the Mg concentrations immediately after the bolus injection.
The Optimal Concentration of Mg
The high critical limit of Mg is reported as 4.9 ± 2.0 mg/dl in adults and 4.3 ± 1.1 mg/dL in children [8]. SMg concentration in two patients (one in previous Allen’s report [7] and another, patient 4 in the present report) rose to 5 mg/dL and over, but no there were no notable side effects.
When the total bolus dose of Mg exceeds 400 mg in adults and 24 mg/kg in children, the measurement of Mg concentration and careful monitoring are mandatory. We suspect that optimal SMg concentration during Mg therapy may be as high as 3 to 5 mg/dL.
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CONCLUSIONS
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Intravenous infusion of MgSO4 was effective for TdP in children with LQTS. The optimal bolus dosage, infusion rates and SMg concentration were 3 to 12 mg/kg, 0.5 to 1.0 mg/kg/hr and 3 to 5 mg/dL, respectively.
Received August 5, 2004.
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ABSTRACT
INTRODUCTION
