Double-blind, randomized study of the effect of cisapride on gastric emptying in critically ill patients

OBJECTIVESTo investigate the absorption of the gastrokinetic drug, cisapride, and effect of cisapride on gastric emptying in critically ill patients; and to assess the usefulness of clinical signs of gastric emptying. DESIGNProspective, randomized, controlled study. SETTINGMedical/surgical/trauma intensive care unit (ICU) in a university hospital. PATIENTSTwenty-seven consecutively enrolled patients, aged 18 to 65 yrs, with normal hepatic and renal biochemistry who were not receiving enteral nutrition and who had no contraindications to enteral nutrition. These patients were expected to stay in the ICU for at least 4 days. INTERVENTIONSPatients were randomized to receive either placebo or rectal cisapride, 60 mg initially followed by two doses of 30 mg at 8-hr intervals. MEASUREMENTS AND MAIN RESULTSGastric emptying was estimated, using acetaminophen absorption on day 1 of the study. Placebo or cisapride was administered and a second acetaminophen absorption test for gastric emptying was carried out on day 2, 24 hrs after the first test. Four patients were excluded because of incomplete data. Statistical analysis was performed, using the area under the acetaminophen absorption curve from 0 to 60 mins as the primary measure of gastric emptying. There was no significant change in the area under the acetaminophen absorption curve from 0 to 60 mins from day 1 to day 2 in patients who received placebo or cisapride. Using the combination of the time to maximum acetaminophen concentration (12 mg/L) to define "normal" emptying, on day 1, four of the 11 placebo patients had the "normal" gastric emptying, and by day 2, five patients fulfilled this criterion. Before administration of cisapride, four of the 12 patients fulfilled this criterion, whereas nine fulfilled the criterion after receiving cisapride. There was a large variation in gastric emptying from day 1 to day 2; a power calculation suggests that [approximately] 150 patients would have to be studied to determine the effect of cisapride. There was no correlation between gastric emptying and the volume of gastric aspirate or the presence of bowel sounds. Plasma cisapride concentrations 4 hrs after the third dose, during the second acetaminophen absorption test, averaged 53 ng/mL (range 20 to 111). CONCLUSIONSRectal cisapride in the dose given achieved average plasma concentrations similar to those concentrations achieved in healthy subjects after 30 mg of cisapri