Effects of Cisapride on Corrected QT Interval, Heart Rate, and Rhythm in Infants Undergoing Polysomnography

Abstract

ABSTRACT. Objective. To evaluate the effects of cisapride, a prokinetic gastrointestinal drug, on the electrocardiographic QT interval, heart rate, and rhythm in infants during routine 8-hour polysomnography. Reported electrocardiogram (ECG) and rhythm disturbances in a small number of patients with the use of cisapride provided the impetus for this prospective study.Study Design. Two hundred fifty-two infants born at term were enrolled. Of these, 134 were on cisapride therapy for suspected gastroesophageal reflux and 118 were not on cisapride and served as controls. Cisapride-treated and control infants were from the outset divided into 3 age groups; group 1: under 3 months of age; group 2: between 3 and 6 months of age; and group 3: >6 months of age. Continuous ECG bipolar limb lead I recording, saturation monitoring, and electroencephalography were conducted. QT intervals and heart rate were measured at hourly intervals.Results. Cisapride doses were: group 1 mean, 0.80 mg/kg/day (range: 0.38 -1.55); group 2 mean, 0.80 mg/kg/ day (range: 0.23-1.38); and group 3 mean, 0.72 mg/kg/day (range: 0.32-1.41). Heart rate was higher in the younger infants, with a gradual decrease with age. No difference in heart rate was detected between the cisapride and control groups. The QTc interval in patients in group 1 was statistically longer than the controls, when applying both Bazett's and Hodges' formulae for QT correction. The other age groups did not differ. No arrhythmia or atrioventricular conduction abnormalities were observed.Conclusion. Infants under 3 months of age on cisapride treatment had significantly longer QTc intervals (with Bazett's formula, the 98th percentile was 504 ms in the cisapride group vs 447 ms in controls). The clinical significance and risk of the increased QTc interval in these infants are unclear and need further evaluation and risk stratification. Meanwhile, cisapride should be judiciously prescribed in infants <3 months of age. Pediatrics 2000;106(6). URL: http://www.pediatrics.org/ cgi/content/full/106/6/e85; QT interval, QTc, cisapride, heart rate, heart rhythm, infants.ABBREVIATIONS. ECG, electrocardiogram; CYP, cytochrome P-450. C isapride, a prokinetic agent used in adults and children with gastrointestinal motility disorders, has been reported in some patients to increase the QT interval on the electrocardiogram (ECG). 1-3 Prolongation of the electrocardiographic QT interval may be either congenital 4 -6 or acquired. 7 Acquired prolongation of the QT interval can be caused by electrolyte disturbances (commonly hypokalemia and hypocalcemia), hypothermia, central nervous system injury, malnutrition, organophosphate poisoning, and medication. Medications that have been implicated include tricyclic antidepressants, macrolide antibiotics, phenothiazines, and antiarrhythmic agents. 7 The QT interval on the ECG represents the period from the beginning of depolarization (QRS complex) to the end of repolarization (T wave) of the ventricles. There are at least 5 different genes responsible for ...

Efficacy and Tolerability of Cisapride in Children

“…[57][58][59][60][61] This is also confirmed by general surveys in the population. Among 36 743 cisapride users in Canada and the UK, cisapride did not appear to be associated with serious rhythm disorders.…”

“…During the last couple of years, no new risk factors have been identified (see table III for established contraindications and precautions). There is little doubt that cisapride may have a QT-prolonging effect in some circumstances, [8,9,[57][58][59][60][61] as do many other drugs and clinical situations (table III). [56] Cisapride possesses Class III antiarrhythmic properties and prolongs the action potential duration, delaying cardiac repolarisation, [62] although many studies do not report an increase in duration of QTc in neonates or in older children.…”

How accurately can QT interval be measured in newborn infants?

“…An association between a prolonged QTc interval in the 1st week of life and sudden infant death syndrome was reported in 1998 [17] and since 1996, various case reports have mentioned a prolonged QTc interval in association with the use of cisapride, a routinely prescribed gastroprokinetic agent [9,10]. Several prospective studies confirmed an increase in QTc interval following the use of cisapride in preterm neonates and young infants but results are inconsistent and although a relationship could be found between postnatal age, gestational age and QTc prolongation, the clinical importance remains unclear [2,3,5,6,7,8,15,18].…”

24-Hour Electrocardiogram before and during Cisapride Treatment in Neonates and Infants

“…Several proarrhythmia risk factors have been identified: overdose or concomitant use of drugs that are metabolized through the P-450 cytochrome or prolong the Q-T interval, heart disease, electrolyte disturbances, prematurity, and newborn age [15,17]. From a review of the effects of cisapride on the QTc interval, it appears that preterm and term infants younger than 3 months of age are particularly sensitive to the cardiac effects of cisapride (table 6).…”