Emergency department use of oral ondansetron for acute gastroenteritis-related vomiting in infants and children

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Acute gastroenteritis is the most common cause of physician visits and hospitalizations in infants and young children. Each year in the United States, gastroenteritis accounts for approximately two to four million physician visits ^[1][2][3]. The estimated incidence of acute gastroenteritis in children younger than five years of age is approximately one to two episodes annually in industrialized countries ^[4]. In the United States, the disease accounts for 20% of all outpatient visits among younger children, and more than 200,000 hospitalizations per year ^[5].

Acute gastroenteritis is the most common cause of vomiting in children, and is often associated with abdominal pain, cramping, diarrhea and fever ^[6]. It is usually a self-limited infection, and is most commonly caused by viruses such as rotavirus or norovirus ^[2][6]. During the course of illness, many children suffer from an inability to tolerate fluids and solids. Those with persistent vomiting are at risk of dehydration, electrolyte abnormalities and, for the more seriously affected, nasogastric (NG) or intravenous (IV) rehydration therapy and/or hospital admission may be necessary.

Ondansetron – Pharmacology and patterns of use

Antiemetic drugs are frequently used to treat vomiting in infants and children with gastroenteritis. A recent survey ^[7] of paediatricians, emergency physicians and paediatric emergency physicians reported that 61% of physicians had prescribed an antiemetic medication for paediatric gastroenteritis-related vomiting at least once in the previous year. Prescription patterns and use of antiemetic medications such as promethazine, metoclopramide, dimenhydrinate and domperidone vary considerably ^[8][9]. Although rare, worrisome adverse effects such as drowsiness, extrapyramidal reactions, hallucinations, convulsions and neuroleptic malignant syndrome must be considered when prescribing these medications ^[8][9].

Ondansetron is a highly potent and selective serotonin 5-HT3 receptor antagonist. When administered orally, it is rapidly absorbed by the gastrointestinal tract, achieving peak plasma concentrations after only 1 h to 2 h ^[10]-[13]. Ondansetron is safe and effective in preventing chemotherapy- and radiation-induced nausea and vomiting, as well as vomiting in postoperative patients ^[14]-[18]. When used in these clinical circumstances, there is a very low risk of significant adverse effects ^[14]-[18]. When used for gastroenteritis in infants and children, the most common side effect is diarrhea, which is usually quite mild and self-limiting ^[13][19]. While both the Federal Drug Administration and Health Canada have issued warnings regarding the use of ondansetron and fatal arrhythmias ^[20][21], current evidence does not support routine electrocardiogram (ECG) and electrolyte screening before single oral ondansetron dose administration to individuals without known risk factors ^[22]. Due to its favourable safety profile and absence of drowsiness as a side effect, several clinical trials have been conducted in the past 20 years to assess the efficacy of ondansetron use in paediatric gastroenteritis.

Review of paediatric evidence

Four randomized controlled studies ^[23]-[26] that examined the use of oral ondansetron (versus placebo) for vomiting due to acute gastroenteritis are outlined in Table 1. Studies that examined the use of IV ondansetron in acute gastroenteritis were not considered for the purposes of the present review ^[27]-[29]. Two recent meta-analyses, published in 2008 ^[30] and 2015 ^[31], examined the efficacy of various antiemetics and will be discussed below.

In 2008, Roslund et al ^[25] published a study in which they enrolled 106 children one to 10 years of age from a combined adult and paediatric ED (Table 1). Children were recruited if they had a clinical diagnosis of acute gastritis or gastroenteritis, mild to moderate dehydration and had failed controlled oral rehydration in the ED. Subjects were randomly assigned to receive a single weight-based dose of oral ondansetron or placebo, and were restarted on the oral rehydration protocol 30 min later. The investigators found that children who received oral ondansetron were less likely to receive IV fluids and less likely to be admitted to hospital compared with children who received a placebo.

In 2016, Marchetti et al ^[26] published a study in which 356 children from one to six years of age with acute gastroenteritis were randomized to receive either a single dose of oral ondansetron, domperidone or a placebo in the emergency department after failure of initial oral rehydration administration. Oral rehydration was commenced 45 to 60 minutes later. Ondansetron reduced the relative risk of IV hydration by more than 50% compared with both placebo and domperidone. There was no difference in adverse events among the three groups.

DeCamp et al ^[30] published a meta-analysis in 2008 specifically to examine the use of various antiemetic drugs for children with acute gastroenteritis. As part of their analysis, they reviewed six different studies involving ondansetron; three studies described above ^[23]-[25] and three other studies involving the use of IV ondansetron ^[27]-[29]. Their analysis included data obtained from the original publications, as well as data from personal communications with the original authors. The results of their combined analysis of oral and IV ondansetron studies showed that subjects treated with ondansetron were at decreased risk for further emesis in the ED, IV fluid administration and hospital admission (RRs and 95% CIs are reported in Table 1). The most significant adverse event noted from the various studies was an increased risk of diarrhea up to 48 h after administration of ondansetron. No other adverse events were common across all studies.

Freedman et al ^[31] published a systematic review and meta-analysis in 2015 examining gastroenteritis therapies for children <18 years old in developed countries. All studies involving antiemetics demonstrated a reduction in the primary outcome of IV rehydration use. Ondansetron was the antiemetic used in six of these nine studies.

Conclusion

Oral ondansetron therapy, as a single dose for paediatric gastroenteritis, is effective in reducing the frequency of vomiting and IV fluid administration in infants and children six months to 12 years of age who present to the ED with mild to moderate dehydration or who have failed a trial of oral rehydration therapy. Evidence suggests that oral ondansetron may be effective in reducing hospital admissions. The most common side effect of the administration of oral ondansetron in this context is diarrhea, which is usually self-limited in nature and lasts less than 48 h. Further studies are required to address its use and efficacy in the out-of-hospital setting.

Recommendations

Oral ondansetron therapy, as a single dose, should be considered for infants and children age six months and older who present to the ED with vomiting related to suspected acute gastroenteritis, and who have mild to moderate dehydration or who have failed oral rehydration therapy. Because the most common side effect of ondansetron is diarrhea, its use is not routinely recommended in children with gastroenteritis whose predominant symptom is moderate to severe diarrhea. Ondansetron dosage is 0.15 mg/kg in liquid format (to a maximum dose of 8 mg). Alternatively, a reasonable weight-based oral dosing regimen for infants and children is the following:

• 8 kg to 15 kg: 2 mg
• 15 kg to 30 kg: 4 mg
• Greater than 30 kg: 6 mg to 8 mg

Oral rehydration therapy should be initiated 15 min to 30 min after administration of oral ondansetron. The use of a single dose of oral ondansetron is recommended, as there are no benefits seen with multi-dose therapy ^[22].

Acknowledgements

The following Canadian Paediatric Society committees reviewed this practice point: Community Paediatrics, Drug Therapy and Hazardous Substances, Infectious Diseases and Immunization, and Nutrition and Gastroenterology.

ACUTE CARE COMMITTEE

Members: Adam Cheng MD; Catherine Farrell MD; Jeremy Friedman MD; Marie Gauthier MD (Board Representative); Angelo Mikrogianakis MD (Chair); Oliva Ortiz-Alvarez MD
Liaisons: Laurel Chauvin-Kimoff MD, Paediatric Emergency Medicine Section, Canadian Paediatric Society; Dawn Hartfield MD, Hospital Paediatrics Section, Canadian Paediatric Society
Principal author: Adam Cheng MD
Updated by: Marie-Joëlle Doré-Bergeron and Laurel Chauvin-Kimoff

References

Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.