Should Ondansetron Be Used for Acute Gastroenteritis?

Patient Presentation
A 6-year-old female came to the clinic with emesis and diarrhea. She had been well but had onset of emesis 10 hours prior to coming to clinic and 2 episodes of loose water stools without blood. The emesis was of fluid and food without blood or a bilious color. The parent had tried some oral rehydration solution (ORS) but the patient had emesis of the fluid so the mother stopped giving it to her. She also started to have diarrhea about 4 hours previously with 2 loose, watery stools without blood. Her last urination was 6 hours ago. She had no obvious ill contacts. The past medical history showed a healthy patient and the review of systems was negative for fever, chills, or cough. The pertinent physical exam showed a tired appearing female with normal vital signs except for a weight that was down 680 grams from a weight 1 month ago. She had mildly dry lips but moist mucous membranes. Her capillary refill was approximately 2 seconds. Her examination was otherwise normal. The diagnosis of acute gastroenteritis with mild dehydration was made. The parent was instructed on how to give ORS and also given 1 dose of oral ondansetron. The patient had emesis once not long after starting the rehydration but then starting feeling somewhat better. By 2-3 hours later she had taken an additional 12 ounces without emesis and had urinated. The patient was sent home with instruction about how to continue to give the ORS, how to restart a regular diet and when to call the clinic.

Acute gastroenteritis (AGE) is a common illness worldwide and is “…defined as a decrease in the consistency of stools (loose or liquid) and/or an increase in the frequency of evacuations with or without fever or vomiting….” It is one of the most common reasons for seeking medical care and hospitalizations. In Europe, rotavirus and noroviruses are two of the most frequent viral agents causing AGE and Campylobacter and Salmonella are the most common bacterial AGE causes. For parasitic infections Giardia, and Crytosporidium are most common parasitic infections in Europe.

Recommendations for AGE treatment include oral rehydration, nasogastric rehydration and or intravenous rehydration. The European Society of Pediatric Gastroentrology, Hepatology, and Nutrition/European Society for Pediatric Infectious Diseases recommends oral and nasogastric rehydration before trying intranveous rehydration. They note that “…oral rehydration is more effective and less invasive than IV rehydration and the administration of [oral rehydration solutions] should be attempted and promoted.” Additionally if IV therapy is used, patients “… should be made to switch or oral rehydration as soon as indication for parental rehydration are no longer observed.” Those indications for IV rehydration include shock, dehydration that is accompanied by a change of consciousness or severe acidosis, worsening dehydration or lack of improvement despite oral or NG rehydration, persistent emesis despite oral or NG therapy or severe abdominal distention and ileus.

According to the European guidelines, in addition to rehydration, some absorbents (i.e. Diosmectite) and antisecretory medication (i.e. Racecadotril) can be considered for AGE, but some agents are not available in all countries. Probiotics (eg. L. rhamnosus GG and S. boulardii) should be considered for use with AGE as an adjunct to rehydration therapy according to these guidelines. Drug therapy that is not recommended includes the antimotiity agent loperamide, the antisecretory agent bismuth subsalicylate, symbiotics, prebiotics, folic acid and gelatine tannate. The guidelines also note that antiinfective therapy is generally not used in the “…vast majority of healthy children with acute gastroenteritis…” and “… is not needed routinely but only for specific pathogens or in defined clinical settings.”

AGE can cause visceral stimulation of the gut causing dopamine and serotonin to be released which in turn causes the medullary vomiting center to be stimulated which thereby causes nausea and emesis. Ondansetron (Zofran®) is a setotonin antagonist (5-HT3 receptor) used to treat this effect. The site of action is not entirely known and may be in the viscera, the medulla or both. A recent retrospective multicenter cohort study from 2002-2011 of the use of ondansetron in pediatric emergency room settings found that ondansetron use increased substantially from 0.11% in 2002 to 42.2% in 2011. Unfortunately there was only a small decrease in the percentage of patients who received IV hydration (18.7% to 17.8%) and hospital admissions increased over the same study period (6.0% to 6.7%). The authors have several ideas as to why this may occur and state “Our findings highlight the need to focus efforts to administer ondansetron to children at greatest risk for oral rehydration failure.”

Learning Point
According to the European guidelines, ondansetron “…may be effective in young children with vomiting related to AGE. Before a final recommendation is made, a clearance on safety in child is however, needed.” This could be given orally or by IV. The Canadian Pediatric Society recommends a single dose be considered for children 6 months – 12 years with emesis caused by AGE plus having mild to moderate dehydration or having failed oral rehydration therapy. A known side effect of ondansetron is diarrhea, therefore it is not recommended for AGE that is primarily due to diarrhea. Patients with electrolyte abnormalities such as hypomagnesemia and hypokalemia may have increased risk of prolongation of the QT interval when receiving ondansetron.

Questions for Further Discussion
1. How has the rotavirus vaccine changed the epidemiology of gastroenteritis in industrialized nations?
2. What causes chronic diarrhea in the pediatric age group?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Gastroenteritis

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

A Cheng. Emergency department use of oral ondansetron for acute gastroenteritis-related vomiting in infants and children. Canadian Paediatric Society, Acute Care Committee.
Paediatr Child Health 2011;16(3):177-9.

Fedorowicz Z, Jagannath VA, Carter B. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. Cochrane Database Syst Rev. 2011 Sep 7;(9):CD005506

Freedman SB, Hall M, Shah SS, Kharbanda AB, Aronson PL, Florin TA, Mistry RD, Macias CG, Neuman MI.
Impact of increasing ondansetron use on clinical outcomes in children with gastroenteritis. JAMA Pediatr. 2014 Apr;168(4):321-9.

Keren R. Ondansetron for acute gastroenteritis: a failure of knowledge translation. JAMA Pediatr. 2014 Apr;168(4):308-9.

Guarino A, Ashkenazi S, Gendrel D, Lo Vecchio A, Shamir R, Szajewska H. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Society for Pediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe: update 2014.
J Pediatr Gastroenterol Nutr. 2014 Jul;59(1):132-52. Ondansetron Clinical Pharmacology.
Available from the Internet at (rev. 11/7/2014, cited 7/13/2015).

Flake ZA, Linn BS, Hornecker JR. Practical selection of antiemetics in the ambulatory setting. Am Fam Physician. 2015 Mar 1;91(5):293-6.


Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital