DOUBLE-BLIND, RANDOMIZED STUDY OF THE EFFECT OF CISAPRIDE ON GASTRIC-EMPTYING IN CRITICALLY ILL PATIENTS

Objectives: To investigate the absorption of the gastrokinetic drug, c isapride, and effect of cisapride on gastric emptying in critically il l patients; and to assess the usefulness of clinical signs of gastric emptying. Design: Prospective, randomized, controlled study. Setting: Medical/surgical/trauma intensive care unit (ICU) in a university hosp ital. Patients: Twenty-seven consecutively enrolled patients, aged 18 to 65 yrs, with normal hepatic and renal biochemistry who were not rec eiving enteral nutrition and who had no contraindications to enteral n utrition. These patients were expected to stay in the ICU for at least 4 days. Interventions: Patients were randomized to receive either pla cebo or rectal cisapride, 60 mg initially followed by two doses of 30 mg at 8-hr intervals. Measurements and Main Results: Gastric emptying was estimated, using acetaminophen absorption on day 1 of the study. P lacebo or cisapride was administered and a second acetaminophen absorp tion 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 acetami nophen absorption curve from 0 to 60 mins as the primary measure of ga stric 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 i n patients who received placebo or cisapride. Using the combination of the time to maximum acetaminophen concentration (less than or equal t o 30 mins) with a maximum concentration (> 12 mg/L) to define ''normal '' emptying, on day 1, four of the 11 placebo patients had the ''norma l'' gastric emptying, and by day 2, five patients fulfilled this crite rion. Before administration of cisapride, four of the 12 patients fulf illed this criterion, whereas nine fulfilled the criterion after recei ving cisapride. There was a large variation in gastric emptying from d ay 1 to day 2; a power calculation suggests that similar to 150 patien ts would have to be studied to determine the effect of cisapride. Ther e was no correlation between gastric emptying and the volume of gastri c aspirate or the presence of bowel sounds. Plasma cisapride concentra tions 4 hrs after the third dose, during the second acetaminophen abso rption test, averaged 53 ng/mL (range 20 to 111). Conclusions: Rectal cisapride in the dose given achieved average plasma concentrations sim ilar to those concentrations achieved in healthy subjects after 30 mg of cisapride rectally. There is a large variation in gastric emptying from one day to the next and large numbers of patients are required to determine if cisapride administration improves early gastric emptying in critically ill patients. The volume of gastric aspirate and the pr esence of bowel sounds do not correlate with gastric emptying.