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Sequential single doses of cisapride, erythromycin, and metoclopramide in critically ill patients intolerant to enteral nutrition: A randomized, placebo-controlled, crossover study

MacLaren, Robert PharmD; Kuhl, David A. PharmD; Gervasio, Jane M. PharmD; Brown, Rex O. PharmD; Dickerson, Roland N. PharmD; Livingston, Teresa N. PharmD; Swift, Kyle PharmD; Headley, Stacey MD; Kudsk, Kenneth A. MD; Lima, John J. PharmD

Clinical Investigations

Objective: To evaluate the comparative efficacy of enteral cisapride, metoclopramide, erythromycin, and placebo for promoting gastric emptying in critically ill patients with intolerance to gastric enteral nutrition (EN).

Design: A randomized, crossover study.

Setting: Adult medical intensive care unit at a university-affiliated private hospital and trauma intensive care unit at a university teaching hospital.

Patients: Ten adult, critically ill, mechanically ventilated patients not tolerating a fiber-containing EN product defined as a single aspirated gastric residual volume >150 mL or two aspirated gastric residual volumes >120 mL during a 12-hr period.

Interventions: Patients received 10 mg of cisapride, 200 mg of erythromycin ethylsuccinate, 10 mg of metoclopramide, and placebo as 20 mL of sterile water every 12 hrs over 48 hrs. Acetaminophen solution (1000 mg) was administered concurrently. Gastric residual volumes were assessed, and plasma acetaminophen concentrations were serially determined by TDx between 0 and 12 hrs to evaluate gastric emptying.

Measurements and Main Results: Gastric residual volumes during the study were not significantly different between agents. No differences in area under the concentration vs. time curve or elimination rate constant were identified between agents. Metoclopramide and cisapride had a significantly shorter mean residence time of absorption than erythromycin (6.3 ± 4.5 [SEM] mins and 10.9 ± 5.8 vs. 30.1 ± 4.5 mins, respectively [p< .05]). Metoclopramide (9.7 ± 15.3 mins) had a significantly shorter time to peak concentration compared with erythromycin and placebo (60.7 ± 8.1 and 50.9 ± 13.5 mins, respectively [p< .05]). The time to onset of absorption was significantly shorter for metoclopramide vs. cisapride (5.7 ± 4.5 vs. 22.9 ± 5.7 mins [p< .05]).

Conclusion: In critically ill patients intolerant to EN, single enteral doses of metoclopramide or cisapride are effective for promoting gastric emptying in critically ill patients with gastric motility dysfunction. Additionally, metoclopramide may provide a quicker onset than cisapride.

From the College of Pharmacy, Dalhousie University, NS, Canada (Dr. MacLaren); the College of Pharmacy, the Department of Clinical Pharmacy (Drs. Kuhl, Gervasio, Brown, Dickerson, Livingston, Swift, and Lima), and the College of Medicine, the Departments of Pulmonary and Critical Care Medicine (Dr. Headley) and Surgery (Dr. Kudsk), University of Tennessee, Memphis, TN; and the Department of Pharmacy Services, Baptist Memorial Health Care Corporation, Memphis, TN (Dr. Kuhl).

Supported, in part, by research funds available through the Department of Clinical Pharmacy, University of Tennessee, Memphis, TN.

Address requests for reprints to: David A. Kuhl, PharmD, Department of Pharmacy Services, Baptist Memorial Hospital, 899 Madison Avenue, Memphis, TN 38146. E-mail:

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