Gastro-oesophageal reflux is the movement of stomach contents back into the oesophagus. A ring of smooth muscle (sphincter) at the lower end of the oesophagus near the stomach usually prevents this regurgitation. Relaxation of the sphincter, ineffective clearance of food from the oesophagus into the stomach, and delayed emptying of the stomach can all contribute to reflux. The peak incidence of reflux is generally at around four months of age and resolves by one to two years. Parents may seek medical help for the reflux if they are anxious or find the symptoms of regurgitation, crying, irritability, vomiting and, gagging difficult to tolerate. Some young children experience associated respiratory problems of chronic cough, wheezing, hoarseness, recurring bronchitis, pneumonia, apnoea or breath holding; and back-arching, refusal to feed and sleep disturbance. Inflammation of the oesophagus may be evident with endoscopy or the child may fail to thrive and surgery may be required. Scintigraphy or sonography are used to monitor oesophageal motility.
Attention to the child’s position (by avoiding lying flat or a slumped seated position) and diet (thickened feeds, frequent small meals, non-prescription stabilisers such as Gaviscon) may be effective in reducing reflux. Medications include prokinetic drugs given before a meal to stimulate gut motility and acid-secretion inhibitors. Cisapride is a prokinetic drug used to improve symptoms and avoid serious complications of reflux. From this systematic review, we found no clear evidence of reduced symptoms of reflux with cisapride compared to placebo or no treatment. The parent or guardian of the child or the treating physician assessed the symptoms (regurgitation, crying, irritability, vomiting, gagging) at the end of treatment. Nine trials compared cisapride with placebo or no treatment, of which eight (262 participants) reported data on symptoms of gastro-oesophageal reflux in children aged between five days and five years. They were followed up for two weeks to eight weeks.
Investigations of reflux can include oesophageal pH monitoring for 18 to 24 hours to determine the number of episodes of pH < 4, duration of the longest episode of pH < 4 and the presence of sleep reflux. These pH measurements poorly correlate with symptoms and responses of a child to treatment.
Cisapride significantly reduced the percentage of time the pH < 4 (reflux index) but not other measures of oesophageal pH monitoring
Fatal cardiac arrhythmia or sudden death have been associated with cisapride use in children and it is only used within restricted programmes under specialist supervision. One multicentre study of 134 children found no electrocardiographic QTc interval changes with cisapride.
We found no clear evidence that cisapride reduces symptoms of GOR. Due to reports of fatal cardiac arrhythmias or sudden death, from July 2000 in the USA and Europe cisapride was restricted to a limited access programme supervised by a paediatric gastrologist.
Gastro-oesophageal reflux (GOR) is common and usually self-limiting in infants. Cisapride, a pro-kinetic agent, was commonly prescribed until reports of possible serious adverse events were associated with its use.
To determine the effectiveness of cisapride versus placebo or non-surgical treatments for symptoms of GOR.
We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Specialised Register and Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, reference lists of relevant review articles and searched in the Science Citation Index for all the trials identified. All searches were updated in February 2009.
Randomised controlled trials comparing oral cisapride therapy with placebo or other non-surgical treatments for children diagnosed with GOR were included. We excluded trials with a majority of participants less than 28 days of age.
Primary outcomes were a change in symptoms at the end of treatment, presence of adverse events, occurrence of clinical complications and weight gain. Secondary outcomes included physiological measures of GOR or histological evidence of oesophagitis. We dichotomised symptoms into 'same or worse' versus 'improved' and calculated summary odds ratios (OR). Continuous measures of GOR (for example reflux index) were summarised as a weighted mean difference. All outcomes were analysed using a random-effects method.
Ten trials in total met the inclusion criteria. Nine trials compared cisapride with placebo or no treatment, of which eight (262 participants) reported data on symptoms of gastro-oesophageal reflux. There was no statistically significant difference between the two interventions (OR 0.34; 95% CI 0.10 to 1.19) for 'same or worse' versus 'improved symptoms' at the end of treatment. There was significant heterogeneity between the studies, suggesting publication bias. Four studies reported adverse events (mainly diarrhoea); this difference was not statistically significant (OR 1.80; 95% CI 0.87 to 3.70). Another trial found no difference in the electrocardiographic QTc interval after three to eight weeks of treatment. Cisapride significantly reduced the reflux index (weighted mean difference -6.49; 95% CI -10.13 to -2.85; P = 0.0005). Other measures of oesophageal pH monitoring did not reach significance. One included study compared cisapride with Gaviscon (with no statistically significant difference). One small study found no evidence of benefit on frequency of regurgitation or weight gain after treatment with cisapride versus no treatment, carob bean or corn syrup thickeners.