Cisapride associated with QTc prolongation in very low birth weight preterm infants
A Dubin1, M Kikkert, M Mirmiran
1Division of Pediatric Cardiology, Department of Pediatrics, Stanford University, Stanford, California, USA. amdubin@leland.stanford.edu
Insights
Cisapride therapy in preterm infants, especially those less than 32 weeks gestation, significantly prolonged the QT and JTc intervals. This increases the risk of arrhythmias in premature neonates.
Area of Science:
- Neonatal cardiology
- Pediatric pharmacology
- Clinical electrocardiology
Background:
- Cisapride was frequently used in preterm infants to aid enteral feeding and reduce reflux.
- The drug's effect on cardiac repolarization in this vulnerable population has not been systematically studied.
- Concerns about QT interval prolongation led to cisapride's withdrawal by the FDA.
Purpose of the Study:
- To evaluate the impact of recommended cisapride doses on the QT interval in premature infants.
- To assess the incidence of QT and JTc interval prolongation in this cohort.
Main Methods:
- Prospective, blinded electrocardiogram analysis in 25 preterm infants.
- Measurements included QT, JT, QTc, and JTc intervals before and after cisapride administration.
- Infants received either 0.1 mg/kg/dose or 0.2 mg/kg/dose of cisapride.
Main Results:
- 48% of infants (12/25) exhibited repolarization abnormalities.
- QTc prolongation (≥0.450 seconds) occurred in 32% of infants, and JTc prolongation (≥0.360 seconds) in 40%.
- Infants <32 weeks gestation showed a significant QTc prolongation from 0.41 ± 0.02 to 0.44 ± 0.02 seconds.
Conclusions:
- Recommended cisapride doses significantly prolonged QTc and JTc intervals in preterm infants, particularly those <32 weeks.
- A substantial percentage of infants developed prolonged QTc (32%) and JTc (40%) intervals.
- Higher prematurity correlated with an increased risk of QTc prolongation and potential arrhythmias.
Objective:
No systematic study has been performed to evaluate the effect of cisapride on the QT interval in premature infants. Cisapride, which has recently been withdrawn by the Food and Drug Administration and is no longer an approved therapy, was commonly used for preterm infant care to improve the advance of enteral feedings and to reduce reflux and associated apnea. Our aim was to evaluate the effect of recommended doses of cisapride on the QT interval in this population.
Study Design:
Prospective blinded evaluation of electrocardiogram for QT, JT, QTc, and JTc measurements in 25 preterm infants before and after cisapride administration.
Results:
Twelve of 25 infants (48%) developed repolarization abnormalities with cisapride administration: 32% of the infants (8/25) studied had QTc prolongation (>/=0.450 seconds), whereas 10/25 had JTc prolongation (>/=0.360 seconds). Preterm infants <32 weeks significantly prolonged their QTc interval from 0.41 +/- 0.02 to 0.44 +/- 0.02. The QTc and/or JTc was prolonged in 54% of infants receiving 0.1 mg/kg/dose and 42% receiving 0.2 mg/kg/dose.
Conclusions:
The QTc and JTc interval significantly prolonged in preterm infants <32 weeks on the recommended dose of cisapride therapy. A QTc >/=0.450 seconds developed in 32% of infants treated with cisapride, whereas the JTc prolonged in 40%. A significant percentage of infants (54%) developed prolonged QTc intervals at a dose of 0.1 mg/kg/dose. From these data we conclude that there is a higher risk of prolongation of the QTc interval and risk of arrhythmias with greater prematurity.
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