Effect of cisapride on the QT interval in infants with gastroesophageal reflux.

OBJECTIVE We prospectively studied the effect of cisapride per se on QT interval in young infants (3-6 months) with gastroesophageal reflux (GER) in a controlled setting. STUDY DESIGN The infants diagnosed with GER and deemed to require therapy with cisapride were divided into 2 groups. Group A comprised infants with GER who underwent an electrocardiogram (ECG) before initiation of therapy with cisapride in the dose of 1 mg per kg per 24 hours, divided into 3 doses. They were reweighed after 7 to 10 days, and the dose was adjusted for their new weight. A repeat ECG was performed after approximately 2 weeks (12-18 days) of therapy. The QT interval was measured in each ECG and then the corrected QT interval was calculated by Bazett's formula. Group B comprised infants with GER who had already been on therapy with cisapride for over 1 month. All infants in group B received cisapride in an approximate dose of 1 mg per kg per 24 hours (.8-1.1 mg/kg/24 hours) given in 3 divided doses. They underwent only 1 ECG, ie, at 1 to 4 months after initiation of therapy. The measurement of the actual dose of cisapride was demonstrated to every parent and a marked measuring syringe was provided. The following categories of infants were not included: those with any underlying cardiopulmonary, renal, or hepatic problem; those with a history of apnea; those using a macrolide antibiotic or azole antifungal at any stage during the study; and infants hospitalized for any reason during the course of the study. RESULTS Cisapride therapy in the dose of 1 mg/kg/day frequently resulted in a slight increase in the QT interval (pretreatment: 390 +/- 18 milliseconds; posttreatment: 400 +/- 20 milliseconds) but the increase was still below the accepted upper limit of 440 milliseconds and not statistically significant. Even with prolonged therapy, the pattern of change in QT interval was similar to that with therapy for 2 weeks. Overall, 2 of 100 (2%) infants developed a prolongation of corrected QT interval beyond the normal range (456 and 486 milliseconds). Neither infant had evidence of any arrhythmia or conduction defect on ECG. No additional factor could be identified in either infant to explain prolongation of the QT interval. CONCLUSION Our experience suggests that cautious cisapride therapy in young infants in a modest dose does not result in arrhythmias or conduction defects. We recommend that: 1) the dose of cisapride in infants be <1.2 mg/kg/day and preferably between.8 and 1 mg/kg/day; 2) the right measure of the dose be actually demonstrated to the parents; and 3) parents be provided a list of drug interactions with cisapride. One should think twice before denying the use of an effective drug simply because of the need for closer monitoring and extra time spent for parent education.