University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• In children and adolescents with gastroenteritis, does centrally-acting ondansetron decrease vomiting?

Clinical Bottom Lines

Summary of Key Evidence

1. A randomized, double-blind, placebo-controlled trial of a single dose of IV ondansetron was conducted in a pediatric emergency department. The patients recruited were 107 children aged 3 months to 22 years with gastroenteritis who required IV fluid hydration.¹
2. 54 patients were randomized to the study group and received one dose of 0.15 mg/kg intravenous ondansetron; the control group received equivalent volumes of intravenous normal saline as placebo. Both groups received 20 cc/kg normal saline bolus followed by D5 ½ NS at twice maintenance rate. Telephone interviews provided follow-up data collection on 100% of the patients. The patients were followed until they were symptom-free for at least 24 hours.
3. There was a statistically significant increase in the number of patients with no further emesis following drug administration compared to control. 70% of the patients in the ondansetron group had cessation of vomiting following administration of the drug and fluid bolus; 51% of the control group also had cessation of vomiting following fluid bolus alone (P=0.04).
4. Of the patients who did not cease vomiting following drug/placebo administration, there was no statistically significant difference in the median number of episodes of emesis between the groups (2 times in the ondansetron group, compared to 4 times in the placebo group; P=0.25).

Additional Comments

• Clinical Relevance:
  -Approximately 30 million children in the US develop acute gastroenteritis per year. 3 million of these children seek evaluation by physicians, and 220,000 children younger than 5 years are hospitalized each year, accounting for more than 900,000 hospital days.^1,2
• Current AAP Recommendations:
  -Previous clinical experience with antiemetics, including prochlorperazine, promethazine hydrochloride, and metoclopramide, had found the adverse effects such as sedation and extrapyramidal reactions, to be prohibitive for routine treatment of acute gastroenteritis.3 The most recent AAP guidelines for the management of acute gastroenteritis in young children do not recommend antiemetics or antidiarrheal pharmacologic agents.2
  -The AAP recommends oral rehydration therapy as the first choice for patients with mild to moderate dehydration (3-5%). IV fluids are recommended for all patients with severe dehydration (10%) or moderate dehydration with persistent vomiting.²
• Limitations of Study:
  -Although the patients were randomized to the ondansetron and placebo groups, there were a greater number of patients with pre-treatment serum CO2 levels of <15 assigned to the study group (20, compared to 4 patients assigned to the placebo group; P<0.01). This suggests that the randomization process may not have successfully produced equivalent study and placebo groups, and that there may be other potentially confounding factors that were poorly controlled by the randomization process.
  -The patients were to keep symptom journals, but only 40% of the patients returned journals. Although the researchers were successful in contacting all patients for follow-up, the study may have been limited by inaccuracies in recall of symptoms by family members.
  -A large proportion of both groups had no emesis following administration of IV fluids. The researchers also did not discuss when patients resumed oral intake, and whether continuation of vomiting may have been influenced by oral intake.
• Ondansetron is relatively well tolerated. The most common adverse effects have been headache (6-27% among patients using the drug for chemotherapy or post-operative nausea, 5% among patients using the drug for radiation-induced nausea and vomiting) and constipation (3% among patients using single-day therapy). Most adverse effects were considered mild to moderate in severity.³
• The University of Michigan Medical Center has recently changed from ondansetron to dolasetron on its formulary as the 5-HT3 receptor antagonist of choice.

Citation

1. Reeves JJ, Shannon MW, Fleisher GR. Ondansetron decreases vomiting associated with acute gastroenteritis: a randomized, controlled trial. Pediatrics 2002; 109(4):e62. URL:http://www.pediatrics.org/cgi/content/full/109/4/e62.
2. American Academy of Pediatrics, Provisional Committee on Quality Improvement and Subcommittee on Acute Gastroenteritis. Practice parameter: the management of acute gastroenteritis in young children. Pediatrics 1996; 97:424-435.
3. McEvoly GK, et a.l, eds. AHFS Drug Information 2001. AHFS; 2001:2801-4.

CAT Author: Charmalie Jayasekera, MD, MPH

CAT Appraisers: Gene Golding, MD

Date appraised: November 18, 2002