THE EFFECTS OF CISAPRIDE ON VENTRICULAR REPOLARIZATION IN CHILDREN

Abstract

112 AIMS: Life-threatening ventricular arrhythmias mainly attributed to QTc prolongation have been reported in adults and children using cisapride, a prokinetic agent that facilitates gastrointestinal motility. Recent adult and pediatric case reports have suggested an association of malignant ventricular arrhythmias with administration of cisapride in conjunction with drugs that inhibit its cytochrome P-450 metabolism. Therefore, we prospectively studied infants and children receiving cisapride without any concomitant drug to analyze the time-related effects of cisapride on ventricular repolarization. METHODS: Standard 12-lead resting ECGs were obtained from 20 patients (mean age: 6.1±4.1 years; range 2 months-13 years) before cisapride (0.8-1.2 mg/kg per day) therapy, and after 3rd, 7th days and 1 month of therapy. The QT and the preceding RR intervals of at least one sinus beat (range one to three) were measured in a range of nine to 12 leads, and the mean QT and RR intervals were calculated. The corrected QT interval (QTc) was calculated by the method of Bazett (QTc = QT/√RR). Dispersion of QT and QTc (QTD, QTcD) were defined as the difference between the maximum and minimum QT and QTc intervals occurring in any of the 12 leads. Data from these patients were compared with a control group of 372 normal children. RESULTS: Indications of cisapride therapy included gastroesophageal reflux, chronic constipation and cyclic vomiting. Mean QTc, QTD and QTcD values of patients and controls and the time of the ECG study is presented in the Table. Baseline QTc, QTD and QTcD measurements were not different from control group. Mean QTc values 7th day and 1 month of cisapride therapy were significantly higher from control group (p < 0.01 and < 0.001). Mean QTc at 7th day and 1 month of therapy were also found significantly higher than that of baseline value (p < 0.05 and < 0.01). Mean QTD and mean QTcD values during the cisapride treatment were not different from baseline values and controls. Only two patients (2 and 8 months old) had prolongation of QTc (> 450 ms) at 1 month of therapy. One patient had increased QTD (> 50 ms), and 3 patients had increased QTcD (> 80 ms) according to upper limits of control group.TableCONCLUSIONS: The results of this study suggest that cisapride treatment may cause prolongation of ventricular repolarization without causing increased heterogeneity of repolarization (QT dispersion). Small infants may be more vulnerable to this effect because of reduced activity of p-450 enzyme system. However, clinical significance of these findings are unclear, because all the patients in this study group have been asymptomatic without signs of arrhythmia.