Letters to the Editor
Indian Pediatrics 2001; 38: 108-110
Cisapride Use in Preterms
However, we need certain clarifications. Firstly, it is not clear from the study whether the placebo used in the study contained the same base as in Cisapride preparation as any difference in composition will have a bearing on the final outcome. Secondly, was the drug administered at the time of feeding or some time before feeding, since the peak level of cisapride is effected if taken with food(2). Lastly, while undergoing nuclear scan study, was Tc99 phytate administered at a fixed time in each baby to minimize the effect of circadian rhythm?
There are only few double blind studies on the use of cisapride in preterm neonates(3,4). In one such study(3), the time taken to tolerate full enteral feeds was unaltered by Cisapride as compared to placebo, but large gastric residua did seem to be significantly reduced. The author concluded that its use may be appropriate in neonates with significant gastric stasis or regurgitation. Contrary to this, in a recent study(4). Cisapride used for clinically diagnosed cases of gastroesophageal reflux (GER) and feed intolerance didnít demonstrate any benefit; rather it worsened the GER as reaffirmed the current study. One plausible explanation for the ineffectiveness of Cisapride on preterm neonates could be its action on intestinal receptors. Cisapride acts by stimula-tion of 6-Hydroxytyptamine (5-HT4) intesti-nal receptors. It has been suggeted on basis of animal model that 5 HT4 receptors have differing affinities for Cisapride(5). Hence, stimulation of high affinity receptors seemed to increase gastrointestinal motor activity while that of low receptors had the opposite effect. It is quite possible that in the gastrointestinal tract of the preterm neonates, only low affinity receptors have developed sufficiently to be stimulated by Cisapride. Alternatively, the dose of Cisapride used in the current study (within the quoted recommended ranges) may have been too high for the babies and may have resulted in stimulation of low affinity receptors.
We as neonatologists and pediatricians working in nursery, are routinely using Cisapride for feed intolerance and GER in preterm neonates and we are not sure how many of us are using it under cardiac monitoring. In view of the conflicting reports of benefit of Cisapride in preterm neonates, we feel that it should not be used in normal preterm neonates and we fully agree with the authors that multicentric trials are necessary betore it can be prescribed in preterm neonates for feed intolerance and GER. Moreover, in UK, the Medicines Control Agency has stated that Cisapride is contraindicated in neonates born before 36 weeks of gestation until they are 3 months of age due to its fatal side effects(3). So are we really justified in using cisapride in preterm neonates?
We agree that till now there are conflicting reports of efficay of Cisapride in preterm neonates. But if we consider all randomized controlled studies published till now, (includ-ing ours) only one study has shown a beneficial effect(1). All other have shown either no effect(2,3) or negative effect(4). Thus, we believe that efficacy for which we are using Cisapride in neonates is of doubtful nature.
We obtained the drug and placebo from a pharmaceutical company, who provided the placebo with the same base without the drug. The drug was administered along with feeds in all babies at 8 hourly intervals. The nuclear scan was performed in all babies at a fixed time slot in the afternoon (3.00-6.00 p.m.). The drug or placebo was administered approximately two hours prior to nuclear scan (the timing of peak level of Cisapride).
Safety of Cisapride in neonates is not yet settled. There are serious concerns and conflicting views(5,6). Not surprisingly FDA has withdrawn the drug from the US market. Cisapride can be associated with serious side-effects if used inappropriately especially in preterm neonates. Thus Cisapride should be used, if at all, judiciously and under close monitoring(7).