To the Editor: In the last two years several reports published in this journal have addressed the use of cisapride in idiopathic chronic constipation of childhood. The results of these studies are conflicting. An improvement of symptoms with an increase of stool frequency, an increase in the number of stools with normal consistency in severe cases and a decrease of laxative use are reported by some investigators (1-3). In contrast, the most recent study by Odeka et al., "Use of cisapride in treatment of constipation in children," could not demonstrate a clinical role for the use of cisapride in idiopathic constipation(4). At present the debate seems to be unsettled(5).
It is remarkable that in all these studies no clarification is given whether cisapride is administered in tablet or suspension form. Recently, Feldstein reported on the carbohydrate and alcohol content in a large selection of popular oral liquid medication (6). Manufacturers are not obliged to include inactive ingredients in product labelling (7). Therefore, with the exception of alcohol, the quantification of other constituents such as sweetening agents is difficult to obtain. The concentrations of glycerin, sucrose and sorbitol vary considerably from none to very high (6,7). In liquid cisapride, sorbitol content is the highest of all the 200 medications that have been investigated, namely 3.85g/5mL(6).
For many years sorbitol has been used as a laxative with a majority of healthy adults producing watery stools after daily ingestion of 20-30g of a 70% syrup (8). Some adults develop symptoms with as little as 5 to 10g of sorbitol(9,10). Sorbitol absorption is greatly facilitated by glucose or amino acids(11). Consequently, sorbitol absorption after ingestion of a liquid will be less than contained in a meal. On the contrary, in a mixture with fructose, sorbitol malabsorption is more pronounced(12). In the studies on constipation liquid cisapride would provide 0.46g/kg sorbitol per day, a dose that may cause diarrhoea in some children.
Cisapride in liquid form is increasingly used in particular for regurgitation in infants(13). The liquid medication is frequently given to older chronically ill children requiring administration by nasal tube or gastrostomy. Clinicians must consider sorbitol malabsorption with patients having diarrhoea as a side effect of cisapride in liquid form. This form cannot be used in studies addressing cisapride treatment in chronic constipation.
Department of Paediatrics; Bosch Medicentrum; 's-Hertogenbosch; The Netherlands
1. Cucchiara S. Cisapride therapy for gastrointestinal disease. J Pediatr Gastroenterol Nutr
2. Nurko S, Garcia-Aranda JA, Guerrero VY, Worona LB. Treatment of intractable constipation in children: experience with cisapride.J Pediatr Gastroenterol Nutr
3. Staiano A, Cucchiara S, Andreotti MR, Minella R, Manzi G. Effect of cisapride on chronic idiopathic constipation in children.Dig Dis Sci
4. Odeka EB, Sagher F, Miller V, Doig C. Use of cisapride in treatment of constipation in children. J Pediatr Gastroenterol Nutr
5. Loening-Baucke V. Cisapride for children with intractable constipation: an interim verdict. J Pediatr Gastroenterol Nutr
6. Feldstein TJ. Carbohydrate and alcohol content of 200 oral liquid medications for use in patients receiving ketogenic diets.Pediatrics
7. Johnston KR, Govel LA, Andritz MH. Gastrointestinal effects of sorbitol as an additive in liquid medications. Am J Med
8. Ellis FW, Krantz JC. Metabolism and toxicity studies with mannitol and sorbitol in man and in animals. J Biol Chem
9. Hyams JS. Sorbitol intolerance: an unappreciated cause of functional gastrointestinal complaints. Gastroenterology
10. Jain NK, Rosenberg DB, Ullahannan MJ, Glasser MJ, Pitchumoni CS. Sorbitol intolerance in adults. Am J Gastroenterol
11. Hoekstra JH, van den Aker JHL. Facilitating effect of amino acids on fructose and sorbitol absorption in children. J Pediatr Gastroenterol Nutr
12. Rumessen JJ, Gudmand-Hoyer E. Functional bowel disease: malabsorption and abdominal distress after ingestion of fructose, sorbitol and fructose-sorbitol mixtures. Gastroenterology
13. Vandenplas Y, Belli D, Benhamou P, et al. A critical appraisal of current management practices for infant regurgitation-recommendations of a working party. Eur J Pediatr