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Effects of cisapride on ventricular repolarization in children
H E Tutar1, A Kansu, A G Kalayci
1Department of Pediatric Cardiology, Ankara University Medical School, Turkey. tutor@dialup.ankara.edu.tr
Insights
Cisapride treatment in children prolongs ventricular repolarization (QTc), but does not increase QT dispersion, even at higher doses. This effect was observed without any reported clinical adverse events or arrhythmias in the study group.
Area of Science:
- Cardiology
- Pediatric Pharmacology
- Clinical Electrophysiology
Background:
- Cisapride, a prokinetic agent, has been linked to life-threatening ventricular dysrhythmias due to QTc prolongation.
- Concomitant use of cisapride with CYP450 inhibitors may increase the risk of malignant ventricular dysrhythmias.
Purpose of the Study:
- To prospectively evaluate the time- and dose-dependent effects of cisapride on ventricular repolarization in infants and children.
- To assess changes in corrected QT interval (QTc) and QT dispersion (QTD, QTcD) during cisapride therapy.
Main Methods:
- Prospective study of 38 pediatric patients receiving cisapride (0.8-1.2 mg/kg/d) without other medications.
- Standard 12-lead ECGs were recorded at baseline, 3 days, 7 days, and 1 month after initiating cisapride.
- Comparison with a control group of 372 healthy children; patients divided into low-dose (0.8 mg/kg/d) and high-dose (1.2 mg/kg/d) groups.
Main Results:
- Mean QTc values were significantly higher in the cisapride group at 7 days and 1 month compared to baseline and controls (p < 0.001).
- Higher cisapride doses (1.2 mg/kg/d) showed a more significant QTc increase from baseline at 1 month (p < 0.05).
- No significant differences were found in mean QTD or QTcD between the cisapride groups, baseline, or controls.
Conclusions:
- Cisapride therapy in children can lead to prolongation of ventricular repolarization (increased QTc).
- Cisapride does not appear to increase heterogeneity of repolarization (QT dispersion) in pediatric patients.
- The clinical significance of cisapride-induced QTc prolongation remains unclear as no adverse cardiac events were observed in this study.
Abstract:
Life-threatening ventricular dysrhythmias mainly attributed to QTc prolongation have been reported in adults and children who were using cisapride, a prokinetic agent that facilitates gastrointestinal motility. Recent adult and paediatric case reports have suggested an association of malignant ventricular dysrhythmias with administration of cisapride in conjunction with drugs that inhibit its cytochrome P-450 metabolism. Therefore, to analyse the time- and dose-related effects of cisapride on ventricular repolarization, we prospectively studied infants and children receiving cisapride with no concomitant medications. Standard 12-lead resting ECGs were obtained from 38 patients (mean age: 6.6 +/- 4.4 y) before the first dose of cisapride (0.8-1.2 mg/kg/d) therapy, and 3 d, 7 d and 1 mo after the first dose of continuing cisapride therapy. The corrected QT interval (QTc), dispersion of QT and QTc (QTD, QTcD) were calculated. Patients were divided into two groups according to dose of cisapride: Group 1 (n = 22) (0.8 mg/kg/d), Group 2 (n = 16) (1.2 mg/ kg/d). Data obtained from these patients were compared with a control group consisting of 372 normal children. No clinical adverse effects such as palpitations, presyncope or syncope were noted during the study. Baseline QTc, QTD and QTcD measurements of the study group were not different from those of the control group. Mean QTc values of the study group on days 7 and 30 of cisapride therapy were found to be significantly higher than those of the control group (p < 0.001 and <0.0001, respectively). Mean QTc values of the study group on days 7 and 30 of therapy were also significantly higher than those of baseline value (p < 0.01 and <0.001, respectively). Mean QTD and mean QTcD values that were recorded throughout the cisapride treatment in the study group were not found to be different from the baseline values and the values of the controls. Mean QTD and QTcD were also not found to be different between Groups 1 and 2. However, mean QTc was found to be more significantly increased from baseline at the first month of therapy in Group 2 (p < 0.05). The results of this study suggest that cisapride treatment cause prolongation of ventricular repolarization without causing increased heterogeneity of repolarization (QT dispersion). However, the clinical significance of this effect is unclear, because all the patients in this study group remained asymptomatic, without signs of dysrhythmia.