Chances are you will be seeing a patient with vomiting during your next shift in the ED. That vomiting may very well be caused by a case of acute gastroenteritis (AGE). You’ve probably written for, and also prescribed ondansetron (Zofran) – perhaps in a reflexive fashion. As with many therapies that have become accepted into routine practice I think that it important to delve into the evidence as to why this is the case. So, without further ado, let’s look at the use of ondansetron to treat vomiting in acute gastroenteritis.

A brief review of pharmacology

Ondansteron, AKA Zofran is a serotonin 5-HT3 receptor antagonist. These receptors are located in terminal of the vagus nerve in the gut and in the brain. Specific cells in the small intestine produce serotonin in response to vomit-inducing stimuli. Blocking the serotonin receptors thus preventing vomiting. The dose is generally 0.15 mg/kg PO or IV. Oral forms are available as a solution or oral dissolving tablet. If you want to keep things simple you could dose in the following manner:

  • 2 mg for children weighing 8 to 15 kg
  • 4 mg for children weighing >15 to 30 kg
  • 8 mg for children weighing >30 kg

The  side effects include diarrhea, urticaria, headache, constipation, and fever. It is contraindicated in patients at risk for malignant hyperthermia and in those with history of prolonged QTc. EKG changes can occur with all 5-HT3 antagonists. Patients especially at risk include those with hypokalemia or hypomagnesemia, heart failure, bradyarrhythmias and those on other medications that increase the risk of QTc prolongation.

The evidence

It is not surprising (especially to readers of the blog) that I would first cite a systematic review. DeCamp et al in JAMA Pediatrics, 2008 identified 11 trials of antiemetics to reduce vomiting in kids with AGE. Six of these compared ondansetron to placebo. Let’s look at each in turn, in chronological order, before moving on to the conclusions.

Cubeddu et al. Aliment Pharmacol Ther, 1997

Three groups of 12 patients were randomized in a parallel fashion to get a single i.v. dose of ondansetron (0.3 mg/kg), metoclopramide (0.3 mg/kg) or placebo (saline). Patients received primarily oral rehydration via fluids over a 24 hour period. In this small trial the authors found that:

  • Patients that received ondansetron vomited less – mean of 2 episodes versus 5 with placebo (p = 0.048)
  • Patients that received ondansetron were more likely to not vomit at all 58% versus 17% placebo (p – 0.039)
  • The antiemetic groups saw more diarrhea, and fewer treatment failures versus placebo overall

Reeves et al. Pediatrics, 2002

This randomized, double blind, placebo-controlled trial in a pediatric ED of patient 1 month to 22 years included patients needing IV fluids for AGE. They were randomized to either IV ondansetron or placebo. The investigators assessed for frequency of vomiting, admission rate, and occurrence of complications.

  • More ondansetron patients stopped vomiting (70% vs 51%)
  • More placebo patients were admitted (30% vs 26%)
  • Subanalysis of patients with CO2 ≥15 mEq/L showed a greater proportion of the placebo group requiring admission (23% vs 7%)

Ramsook et al. Ann Emerg Med, 2002

This double-blind RCT prospectively examined children between the ages of 6 months and 12 years who had vomited at least 5 times in the last 24 hours. They received oral ondansetron or placebo. ORT started 15 minutes later at 5 mL/min. Oral rehydration was commenced 15 minutes later at 5 mL/min. Treatment failure was defined as patients necessitating admission. Kids that were sent home did so with recommendations to do oral rehydration at home with the introduction of a bananas, rice, applesauce, and toast (BRAT) diet after the first 24 hours. The discharged patients also got 5 doses of either ondansetron or placebo. Phone follow up occurred at 24 and 48 hours and parents were queried on the number of episodes of vomiting and diarrhea. Parents also kept a diary of the same. Ultimately they found the following:

  • Ondansetron patients vomited less in the ED (p =.001)
  • There was no significant difference in the number of episodes of vomiting during the first 48 hour follow up period
  • Ondansetron patients had more diarrhea during the follow up period
  • Ondansetron patients needed IV fluids less frequently (p =.015)
  • The admission rate was lower in the ondansetron group (p =.007)
  • The revisit rate was higher in the ondansetron group vs placebo (p =.047)

It is important to note that in either group the median number of episodes of vomiting int he ED and at home was actually zero. They assessed for the rank sum (comparing the continuous distribution of number of episodes of vomiting). This was a viable alternative since so few patients vomited.

Freedman et al. NEJM, 2006

This double blind RCT compared ondansetron ODT vs placebo in children with mild to moderate dehydration due to emesis. 15 minutes after administration they began a oral rehydration therapy based protocol. The children that received ondansetron were:

  • Less likely to have subsequent vomiting (14 vs 35%; p < 0.001) / Number needed to treat to prevent vomiting in one child = 5
  • Vomited less often (0.18 vs 0.65 episodes per child; p < 0.001)
  • Took more oral volume (239 vs 196 ml; p = 0.001)
  • Less likely to get IVF (14 vs 31%; 95% CI: 0.26-20.79) / Number needed to treat to prevent IV fluids in one child = 6
  • There was no difference in the rate of hospitalization or ED return visits

Stork et al. Acad. Emerg Med, 2006

This double-blinded RCT of 166 patients examined IV ondansetron in pediatric ED patients that needed IV fluids after failing ORT. All were mildly to moderately dehydrated. The subjects were ra