0902 Cisapride for reflux in neonates and children

Because of its effects on gastric emptying, a decade ago cisapride was used to treat reflux and regurgitation in some 80% of neonatal units, with reports of up to 40% of neonates being exposed to the drug. This was despite the paucity of evidence in terms of controlled trials. Reports of prolonged QT intervals followed, the problem being aggravated when drug accumulated and particularly if there was coexisting hypokalaemia and/or hypomagnesaemia. Pharmacokinetic studies showed that hepatic immaturity was associated with delayed metabolism in preterm infants, and these factors, together with a Cochrane review which concluded that there was no clear evidence of an effect of the drug on gastro-oesophageal reflux, led to the withdrawal of the drug from general use. However it would seem that certain centres that qualify for controlled use are continuing to use and study the drug. In a recent paper one such centre in Belgium reported on the comparative effects of domperidone and cisapride in an investigator-blinded, prospective study into (a) the frequency of regurgitation, (b) acid reflux and (c) cardiac side effects in infants. The frequency of regurgitation decreased in both groups, more rapidly and significantly in the cisapride group (from 6.22 to 3.50 vs 4.80 to 3.70 in the domperidone group). The decrease was still significant after 1 month (6.22 to 1.55 vs 4.80 to 1.25). However, the similar end points introduce the question of a natural, age-related decrease in regurgitation. Of concern is the fact that one child treated with cisapride developed significant QT prolongation. It is not clear whether the authors are advocating the general reintroduction of the drug, but another recent article speaks in favour of considering its use, not in neonates and young infants but in tube-fed developmentally-impaired children at risk for aspiration pneumonia. Retrospective review of data before and after use of cisapride showed that admission rates and length of stay were both reduced during the months of drug therapy. Their conclusion is that there might be a place for monitored cisapride treatment, however this is unlikely to happen without intensive debate about the safety and benefits vs risks.

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