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Acute gastroenteritis: from guidelines to real life
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Clinical and Experimental Gastroenterology
14 July 2010
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Chung M Chow 1 Abstract: Acute gastroenteritis is a very common disease. It causes significant mortality in
Alexander KC Leung 2 developing countries and significant economic burden to developed countries. Viruses are
Kam L Hon 1 responsible for approximately 70% of episodes of acute gastroenteritis in children and rotavirus
is one of the best studied of these viruses. Oral rehydration therapy is as effective as intravenous
1
Department of Paediatrics,
The Chinese University of therapy in treating mild to moderate dehydration in acute gastroenteritis and is strongly
Hong Kong, Hong Kong Special recommended as the first line therapy. However, the oral rehydration solution is described as an
Administrative Region, PR China;
underused simple solution. Vomiting is one of the main reasons to explain the underuse of oral
2
Department of Pediatrics, The
University of Calgary, Calgary, rehydration therapy. Antiemetics are not routinely recommended in treating acute gastroenteritis,
Alberta, Canada though they are still commonly prescribed. Ondansetron is one of the best studied antiemetics
and its role in enhancing the compliance of oral rehydration therapy and decreasing the rate
of hospitalization has been proved recently. The guidelines regarding the recommendation on
antiemetics have been changed according to the evidence of these recent studies.
Keywords: gastroenteritis, vomiting, antiemetic, ondansetron, rotavirus, oral rehydration
therapy, intravenous therapy, guideline
Introduction
Gastroenteritis is defined as the inflammation of the mucus membranes of the
gastrointestinal tract and is characterized by diarrhea or vomiting. It is a common child-
hood disease. Children in developing countries are particular at risk of both morbidity
and mortality. Worldwide, gastroenteritis affects 3 to 5 billion children each year, and
accounts for 1.5 to 2.5 million deaths per year or 12% of all deaths among children
less than 5 years of age.1–3 In developed countries, such as the United States, acute
gastroenteritis seldom causes deaths, however, it still accounts for 300 deaths per year.2
Moreover, it puts a heavy burden on the health care system. Acute gastroenteritis causes
1.5 million visits to primary care providers each year and 220,000 hospital admis-
sions for children under the age of 5 years; that is 10% of all the hospital admissions
of children in the United States.2 In general, developing countries have a higher rate
of hospital admissions as compared to developed countries. In the United States, the
admission rate is 9 per 1000, per annum, for children younger than 5 years old.4 When
Correspondence: Chung M Chow compared to the United Kingdom and Australia, the admission rates are around 12
Department of Paediatrics, 6/F Clinical to 15 per 1000 per annum.5,6 However, the rate increases dramatically to 26 per 1000
Science Building, Prince of Wales Hospital,
Shatin, Hong Kong Special Administrative per annum in China.7 This may be due to the facts that children in developed coun-
Region, PR China tries have a better nutrition status and better primary care. The difference can also be
Tel +852 26322861
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explained by the fact that, the incidence of acute gastroenteritis is significantly higher
Email [email protected] in developing countries than the industrialized countries.8 Interestingly, Hong Kong
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6554 which permits unrestricted noncommercial use, provided the original work is properly cited.
Chow et al Dovepress
is a developed city, and yet the admission rate is even higher the cause of 205,000 to 272,000 emergency department
than many of the developing countries.9 This may reflect that visits, which results in 55,000 to 70,000 hospitalizations.23
the decision of admission does not simply depend on the In the United States, 1 in 67–85 children will be hospitalized
clinical situations, but it can also be affected by the parents’ because of rotavirus infection by the age of 5 years.24 On the
wishes and other social factors. other hand, Hong Kong has a very high rate of hospitalization.
By the age of 5 years, the cumulative risk is 1 in 24, a figure
Etiology that is 3 times higher than the that of the United States.9
Viruses are the most important etiology and are responsible For each admission in the United States, the hospital costs
for approximately 70% of the episodes of acute gastroenteritis range from $2999 to $3400 with the family costs being $359
in children.10 There are over 20 different types of viruses which includes the caregivers loss of work.24–26 In Hong
that have been identified as etiological agents.11 Worldwide, Kong, admission costs are less expensive although they are
rotavirus is still the most common virus causing this disease not unsubstantial at $1868 (US) for each admission and
and accounts for some 30% to 72% of all the hospitalizations $120 for family expenses.9 Adding in the prevalence of the
and 4% to 24% of acute gastroenteritis at the community disease, gastroenteritis causes a significant economic burden
level.12–15 Virtually all children have been infected with rota- to the health care system. As to the severity of the disease, a
virus by the age of 3 years.16 Rotavirus infection is seasonal study that included 234 hospitalized children infected with
in temperate climates, peaking in late winter, although it rotavirus, 63% of them had diarrhea, vomiting and fever, 21%
occurs throughout the year in the tropics. The peak age for had diarrhea and vomiting, 7% had diarrhea and fever, 4%
infection ranges from 6 months to 2 years. Other common had vomiting and fever, 3% had fever alone, 2% had vomiting
viruses causing gastroenteritis include calicivirus, adenovirus alone and 0.4% had diarrhea alone.27 In general, 90% of the
and astrovirus. Globally these viruses are responsible for hospitalized patients had vomiting. Vomiting is one of the
diarrhea episodes in hospitalized children, with detection most important symptoms for considering failure of oral
rates varying from 3.2%–29.3%, 1%–31%, and 1.8%–16%, rehydration therapy and requiring intravenous therapy.28,29
respectively.17–20 Rates of virus infection are similar in both
developed and less developed countries.21 Bacterial infection Oral rehydration therapy versus
accounts for 10% to 20% of all the acute gastroenteritis.22 intravenous therapy
The most common bacterial causes are, Salmonella species, The American Academy of Pediatrics (AAP), Centers for
Campylobacter species, Shigella species and Yersina species. Disease Control and Prevention (CDC), European Society
Vibrio cholerae remains a major cause of diarrhea, especially for Pediatric Gastroenterology and Nutrition, and the World
after a disaster where sanitation is compromised. Giardia Health Organization (WHO) all strongly support the use
lamblia is the most common protozoal infection that causes of oral rehydration therapy as the first-line therapy for the
gastroenteritis, although it tends to be associated with more treatment of acute gastroenteritis, except in cases of severe
persistent diarrhea. Other protozoa include Cryptosporidium dehydration.2,30–32 The effectiveness of oral rehydration
species and Entamoeba histolytica. However, less developed t herapy in treating acute gastroenteritis, with mild to
countries have a higher rate of parasites and Escherichia moderated dehydration, has been demonstrated by many
coli infection which are both relatively uncommon in the randomized controlled trials. In a Cochrane meta-analysis of
industrialized countries.21 This indicates that improvement 17 trials from 1982 to 2005, in which 9 trials were from the
in sanitation will not decrease the disease prevalence of developed countries, 7 trials from developing countries and
viral infection but can help in prevention of parasites and 1 trial involving developed and less developed countries.33
bacterial infections. Included in this analysis were more than 1800 participants.
The data showed that there were no important clinical
Rotavirus as a prototypic differences between oral hydration therapy and intravenous
virus for gastroenteritis therapy for rehydration secondary to acute gastroenteritis
Rotavirus is a prototypical virus because it is the most common in children; and that children treated with oral rehydration
virus that causes acute gastroenteritis in children which therapy spent less time in hospitals. Moreover, patients
results in hospitalization and treatment with intravenous fluid. receiving intravenous therapy had a 2.5% risk of phlebitis that
According to the data from the United States, approximately did not occur in the oral rehydration group. Importantly, this
410,000 physician visits are due to the rotavirus infection, result is unlikely to change with further trials because there
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Dovepress Acute gastroenteritis: from guidelines to real life
is already adequate power to support the observed results Their responses can be divided into four categories: the
and further research comparing oral rehydration therapy and physician factors; patient factors; parental concern; and
intravenous therapy is not warranted and may be unethical. environment or social factors. Regarding the physician fac-
The effectiveness of oral rehydration therapy is not isolated tors; in contrast to the group of physicians unfamiliar with
to just clinical trials it can also be reflected in the decreased the AAP guidelines, the familiar group was more likely to
mortality rate. In 1970’s the diarrheal illness related deaths use oral rehydration therapy in scenarios of mild dehydration
were 4.6 million/year worldwide.34 After the promotion (81% versus 66%) and moderate dehydration (25% versus
of oral rehydration therapy by World Health Organization 10%). Parental concern about dehydration (disregarding the
(WHO) at the end of 1970’s, the diarrheal illness related death actual hydration status of the patients) would make 31% of
rate dropped to 3.3 million/year in 1980’s, with a further drop the emergency department physicians choose intravenous
to 2.5 million/year in 1990’s.35 therapy over oral rehydration therapy. A crowded or emer-
The oral rehydration solution is regarded as one of gency department with long waiting times would cause 22%
the most important medical advances of the 20th century. of the physicians to choose intravenous therapy. Regarding
Although there is much evidence to support the usage of the severity of dehydration, 49.4% of emergency department
oral rehydration with numerous published guidelines and physicians would offer intravenous therapy even in moderate
many professional organizations recommending its use, dehydration. In terms of symptoms, only 8% of the emer-
oral rehydration solution is still described as an underused gency department physicians would consider intravenous
simple therapy.36 Intravenous therapy is still often chosen therapy when diarrhea was a major symptom. On the other
rather than oral rehydration therapy. Data from Europe, hand, patients refusing to drink was the most likely reason
Australia and Canada show that 80% to 94% of hospitalized for choosing intravenous therapy (up to 96%). Vomiting
children do not have any signs of dehydration and yet they was the second most important reason given for intravenous
still receive intravenous therapy.37–39 Data from Hong Kong, therapy, with up to 85% of the physicians being more likely
that assessed more than 7000 episodes of admission due to to use intravenous therapy when vomiting was the predomi-
gastroenteritis in children under 5 years of age, also showed nant symptom. In another study, up to 36% of the surveyed
that only 1.3% to 8.4% had signs of dehydration and yet up physicians believed that vomiting was a contraindication for
to 48% of the patients received intravenous therapy.40 The oral rehydration therapy.28
rate of intravenous therapy was even higher in the rotavirus Approximately 70% of all children with gastroenteritis also
group. According to a recent survey, 45% of physicians present with vomiting.37 According to our own unpublished
still preferred intravenous fluid therapy rather than oral data ( of more than 7000 episodes of hospitalization in Hong
rehydration therapy in treating moderate dehydration in Kong due to acute gastroenteritis in children younger than
acute gastroenteritis.41 However, judging the effectiveness of 5 years of age) 62% of gastroenteritis patients presented
oral rehydration therapy and the overuse of the intravenous with vomiting. Up to 82% of rotavirus infected children
therapy, any treatments in acute gastroenteritis should presented with vomiting, a figure that was very similar to
improve the success or compliance of oral rehydration the study by Staat and colleagues in 2002.27 In terms of the
therapy as the top priority. Safety and cost are also important episodes and duration of vomiting in gastroenteritis patients,
issues. Successful oral rehydration therapy always means the mean number of vomiting episodes was 4.91/24 hours
that the children can be managed in the community. It is and for a duration of 1.84 days. In summary this may partly
more pleasant for the children and more comfortable for the explain why the oral rehydration solution is an underused
caregivers. Oral rehydration therapy also helps to save money simple solution.
by reducing the hospitalization costs.
The pathophysiology of vomiting
Reasons of underused oral and the mechanisms of antiemetic
rehydration therapy medications
The reasons for the underuse of oral rehydration therapy are Vomiting is usually defined as a violent expulsion of the
not fully understood. In 2002 Ozuah and colleagues published stomach contents through the mouth and being a very
a national random survey of emergency physicians selected unpleasant symptom. It can also be associated with nau-
from the mailing list of the AAP that addressed this issue.29 sea and retching. The mechanism of vomiting has been
A total of 176 physicians responded (73% response rate). well characterized, first by Borison and Wang in 1953.42
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The vomiting center controls and integrates the act of Antiemetic therapy aims at: depressing the vomiting
vomiting. It is located in the lateral reticular formation of center; depressing the chemoreceptor center; inhibiting the
the medulla oblongata, which is close to other centers that impulses from chemoreceptor zone to vomiting center; and/or
regulate respiration, vasomotor, and other autonomic func- inhibiting impulses from peripheral receptors to the vomiting
tions. These centers too may also play an additional role center. All the areas involved in the pathogenesis of vomit-
in vomiting. Emetic stimuli can be transmitted directly to ing are rich in serotoninergic, dopaminergic, histaminic, and
the vomiting center or through the chemoreceptor trigger muscarinic receptors.45 Dopamine antagonists suppress pro-
zone. The chemoreceptor trigger zone, located in the area emetic stimuli by blocking D2 receptors in the chemoreceptor
postrema of the fourth ventricle and outside the blood-brain trigger zone. 5-HT3 antagonists have been more recently
barrier, is exposed to both cerebrospinal fluid and blood.43 developed to block the nausea and vomiting reflexes medi-
This would allow the chemoreceptor trigger zone to pick ated by stimulation of 5-HT3 receptors in both the small
up the chemical signals from both cerebrospinal fluid and intestine and the chemoreceptor center. Antihistamines,
blood stream (such as bacterial toxins or form metabolic although widely used for migraine, are generally recom-
abnormalities that occur with uremia) and act as an afferent mended for motion sickness as they act at the level of the
limb to the vomiting center; however, it cannot indepen- vestibular apparatus.43,52 Anti-cholinergic agents such as
dently mediate the act of vomiting without the interaction of atropine and hyoscine are relatively ineffective in the treat-
vomiting center. On the other hand, the vomiting center does ment or prevention of vomiting due to causes other than
not only receive information from the chemoreceptor trigger motion sickness.52–54 The mechanism of action is not clearly
zone, it can also receive information and stimulation from understood in some antiemetic medications such as dexam-
the cerebral cortex and limbic system, the vestibular system, ethasone and trimethobenzamide.
and the vagal and splanchnic afferents.42,44,45 Psychological
stress such as fear can act on cerebral cortex and limbic The use of antiemetics
system to induce vomiting via the vomiting center. Vomiting in acute gastroenteritis
due to motion sickness develops consequent to stimulation In 1996, the AAP made the following statement: “The
of the vestibular system, with impulses that travel from the committee did not evaluate the use of antiemetic drugs.
labyrinth of the inner ear to the vomiting center. Consensus opinion is that antiemetic drugs are not needed.
However, the exact mechanism of vomiting in Physicians who feel that antiemetic therapy is indicated in a
gastroenteritis is not known; although it is thought to be due given situation should be aware of potential adverse effects”.31
to the peripheral stimuli arising from the gastrointestinal In 2003, the Centers for Disease Control and Prevention
tract primarily via the vagus nerve or via serotonin (CDC) released an updated statement regarding the usage
stimulation of the 5-hydroxytryptamine 3 (5HT3) recep- of antiemetics. It also concluded that antiemetics are usually
tors in the gut.46–49 In acute gastroenteritis, intestinal irrita- unnecessary. Reliance on pharmacologic agents shifts the
tion can damage the gastrointestinal mucosa and result in therapeutic focus away from appropriate fluid, electrolyte,
the release of serotonin from the enterochromaffin cells. and nutritional therapy, that can result in adverse events, and
This serotonin acts on the 5HT3 receptors of the vagal can add unnecessarily to the economic burden of the illness.2
afferent nerves in the gastrointestinal tract,49 which are Notwithstanding the lack of an official recommendation for
then transmitted to the vomiting center directly or via the their use, antiemetics are still commonly prescribed among
chemoreceptor trigger zone. The vomiting center then sends different specialties and countries in the management of
efferent impulses to the diaphragm, abdominal muscles, and acute gastroenteritis.
visceral nerves of the stomach and esophagus to produce Antiemetics are often used because vomiting is an
vomiting.50,51 These events typically include: an increase unpleasant and a distressing symptom which can increase the
in salivation; a decrease in gastric tone that results in the likelihood of dehydration, electrolyte imbalance, pulmonary
sensation of nausea; nonperistaltic contractions in the small aspiration, and most importantly the need for intravenous
intestine; regurgitation of the intestinal contents into the hydration or hospitalization.55–58 The reasons why antiemetics
stomach; contractions of the respiratory and abdominal are not commonly recommended for gastroenteritis related
muscles; and the descent of the diaphragm against a closed vomiting are because vomiting is self-limiting, vomiting
glottis such that the gastric contents are forced up into the is a normal physiological reaction for ridding the body of
esophagus and out through the mouth. toxic substances, and antiemetics can have adverse side
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effects.10,38,59 In addition, the newer antiemetics are also received prescriptions for antiemetic medications (United
costly. States, 23%; Germany, 17%; France, 17%; Spain, 15%; Italy,
O’Loughlin and colleagues prospectively surveyed all 11%; Canada, 3%; United Kingdom, 2%).
children with acute vomiting or diarrhea who were admitted In summary, antiemetic drugs are frequently used
to a pediatric inpatient facility in Newcastle, NSW, Australia, in children with gastroenteritis by physicians in various
during a 12-month period. The authors found that antiemetic specialties and in various countries in spite of the lack of an
medication was administered to 21 (9%) of 231 children official recommendation for their use.
prior to admission.59 Elliott and colleagues found that
antiemetic medications were prescribed for the treatment
of acute gastroenteritis in 9 (5.5%) of 164 children prior to Antiemetic medications
admission to the Royal Alexandra Hospital for Children in Serotonin 5HT3 receptor antagonists
Sydney, NSW, Australia, during a 6-month period.38 Nelson Ondansetron
and colleagues interviewed the caregivers of 105 pediatric Ondansetron is a carbazole derivative that has been available
in-patients with gastroenteritis in Hong Kong where up to since 1991. It is one of the best known potent serotonin 5-HT3
73% had seen one or more primary care practitioners prior receptor-antagonists that blocks receptors at the vagus and
to admission to hospital, and 29% of cases were prescribed sympathetic nerves together with the chemoreceptor trigger
antiemetics.60 zones.64 It has no antidopaminergic properties. The efficacy
In 2002, Kwon and colleagues conducted a national of ondansetron for chemotherapy-induced or postoperative
survey to address this problem in the United States among vomiting in the pediatric population is well documented.65,66
emergency physicians, general pediatricians and pediatric It also has promising effects in patients with vomiting
emergency physicians.61 In this study, 79.2% of emergency due to migraines, procedural sedation with ketamine and
physicians would prescribe antiemetics as compared to 52.2% acetaminophen poisoning.67–69
of general pediatricians and 55.2% of pediatric emergency These positive results initiated investigations for their
physicians. The use of antiemetics by emergency physicians use in gastroenteritis related vomiting. However, only a few
was greater than the other two specialties (P , 0.001). randomized controlled trials regarding its use in pediatric
The most commonly nonexclusive reason for prescribing gastroenteritis have been published. In 2008, DeCamp and
antiemetic use was to prevent the worsening dehydration colleagues published a meta-analysis in order to address this
and the need for subsequent intravenous fluids or admission question.70 The investigators reviewed prospective controlled
(72.0%). This was followed by patient comfort (59.0%), trials only and looked at the emesis cessation, use of
assurance/documentation of oral liquid trial in emergency intravenous fluid for rehydration, hospital admission, return
department/clinic/office before discharge (35.5%), and to care, and medication adverse effects as the principal out-
parental concerns/pressures (29.4%). Albano and colleagues comes. There were 11 articles that met the inclusion criteria.
conducted a similar survey to look at the practice of Italian Ondansetron has the greatest number of studies that met the
hospital pediatricians and family physicians.62 Approximately criteria (n = 6, participants = 745).55,71–75 All of the studies
71% of hospital pediatricians would use antiemetic were conducted in the emergency department setting, except
medications as compared to 96% of the family physicians. the study by Cubeddu and colleagues that was performed in
When comparing the reasons for prescription by family an in-patient setting.55 The majority of studies included only
physicians versus hospital pediatricians, the latter were more children but the study by Reeves and colleagues also included
likely to prescribe antiemetics in order to increase the suc- patients up to 22 years of age.72 Among the six studies,
cess rate of oral rehydration therapy (48%), whereas family the two studies published by Reeves et al and Freedman
physicians prescribed them to increase patient comfort or to et al required dehydration as an inclusion criterion.72,74 The
reduce concerns of parents (46%). study published by Roslund and colleagues and Stork and
Pfeil and colleagues investigated the prescription pattern colleagues, required both dehydration and failure of oral
of antiemetic medications in 0- to 9-year-old children with rehydration as the inclusion criteria.71,75 However, all the
infectious gastroenteritis in several industrialized countries participants in the study by Stork and colleagues received
during 2005.63 The authors retrospectively retrieved data intravenous therapy.71 In all except one study, only one dose
from four national and international databases which showed of ondansetron was administered during the study period.
that between 2% and 23% of children with gastroenteritis The study by Ramsook and colleagues provided families with

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additional doses for home use.73 Routes of administration from the emergency department.72,75 In summary, although an
and dosing varied across studies. There were 3 studies using increase in diarrhea was noted in the ondansetron group up to
intravenous ondansetron. Among these 3 studies, both Stork 48 hours after administration, no difference in frequency was
et al and Reeves et al used a dose of 0.15 mg/kg,71,72 whereas detected afterwards. No other adverse event was systemically
Cubeddu and colleagues used a dose of 0.3 mg/kg.55 Among evaluated and no other adverse effects were common across
the 3 studies of oral ondansetron, Freedman et al and Roslund different studies.
et al used similar weight-based dosing ranging from 2 to The most recent Cochrane meta-analysis was performed
8 mg,74,75 and Ramsook and colleagues used age-based dosing by Alhashimi and colleagues who used very strict inclusion
ranging from 1.6 to 4.0 mg.73 The follow-up period ranged criteria and excluded the studies by Reeves et al and Stork
from 24 hours to 2 weeks. et al.76 The authors came to a similar conclusion, that
Five studies (659 participants) reported whether patients ondansetron may reduce the amount of acute vomiting as well
continued to have emesis in the emergency department after as reducing the number of children who required intravenous
administration of the study drug. Using data from these rehydration, and admission for acute g astroenteritis.
five studies, the relative risk (RR) for vomiting after the However, participants in the ondansetron group did have
ondansetron compared to placebo was 0.45 ( 95% confidence more diarrhea than in the placebo group.
interval [CI]: 0.33–0.62; number needed to treat [NNT] = 5).70 There was one randomized, double blind, placebo
Four studies (489 participants) reported the use of intravenous controlled trial that was published in 2009, however, it was not
fluid. However, the indications for intravenous fluid varied included in the previous meta-analysis.77 This study was also
from study to study and included persistent emesis, refusal performed in emergency department. A total of 109 children
to drink, and persistent or worsening states of dehydration. It aged from 5 months to 8 years who had nonbilious, nonbloody
also showed a statistically significant reduction in the RR of vomiting at least 4 times in the last six hours, who could not
intravenous fluid use for patients who received ondansetron tolerate oral feeding, who had at least 4 episodes of diarrhea
versus placebo (RR, 0.41; 95% CI: 0.28–0.62; NNT = 5).70 in the previous 24 hours, and who had mild to moderate dehy-
Five trials (662 participants) included hospital admission dration were recruited. Oral ondansetron (0.2 mg/kg/dose)
as an outcome. Patients who received ondansetron had a was administered at 8 hourly intervals with a total of 3 doses.
statistically significant decrease in risk of immediate hospital The frequency of vomiting was significantly lower among
admission (RR, 0.52; 95% CI: 0.27–0.95; NNT = 14).70 Five the children who received ondansetron than among those
trials (612 participants) assessed whether patients returned who received placebo (0.36 versus 1.33, P , 0.001 and 0.2
to outpatient care during the study period. Ondansetron versus 1.66, P , 0.001 at four hours and twenty-four hours
use did not significantly affect return to care (RR, 1.34; respectively). Weight gain in the ondansetron group was
95% CI: 0.77–2.35).70 With regard to the RR of admission significantly higher than that of the placebo group at eight
during the whole study period, there was also no significant hours after intervention. At the end of the study, 5.4% (3/55)
difference between the treatment group and the controlled in the ondansetron group and 18.6% (10/54) in the placebo
group (RR, 0.69; 95% CI: 0.43–1.11).70 group failed oral rehydration therapy (RR = 0.29; 95% CI:
Five studies documented the severity of diarrhea after 0.086–1.01; P = 0.04). The authors found that the absolute
ondansetron administration. Overall, three studies have risk of reduction and the number needed to treat were 13.2%
documented an increased severity of diarrhea after the and 8%, in terms of hospitalization and/or intravenous rehy-
ondansetron. Freedman and colleagues reported an increase dration treatment. In terms of side effects, the children who
in diarrhea during the emergency department stay although received ondansetron had more episodes of diarrhea while
they did not evaluate the incidence of diarrhea during follow- undergoing oral rehydration than those who received placebo
up.74 Ramsook and colleagues did not detect any difference at 24 hours (P = 0.04). All of the randomized controlled tri-
in the severity of diarrhea during the emergency department als (RCT) evaluating the efficacy of ondansetron in acute
stay but reported an increase in severity in 48 hours after gastroenteritis are summarized in Table 1.
discharge from the emergency department.73 Cubeddu and The safety profile of ondansetron is favorable, as in the
colleagues also reported more diarrhea episodes in the treatment of gastroenteritis, diarrhea is the most common
24 hours after the ondansetron administration.55 On the other and only reported side effect according to the 7 randomized
hand, the studies by Roslund et al and Reeves et al detected no controlled trials involving 854 participants. However,
differences in diarrheal episodes 5 to 7 days after discharge diarrhea associated with this treatment is usually mild and
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Table 1 Summary of randomized controlled trials evaluating the efficacy of ondansetron in acute gastroenteritis
Source Setting No. Age Inclusion Antiemetic Route/dose of Outcomes Side Follow-
criteria agent ondansetron effects up
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Cubeddu Inpatient 36 6 month GE and .2 × emesis Ondansetron/ IV Vomiting episodes and ORT Increase in 24 hrs
et al 199755 –8 years within 1 hours Metoclopramide 0.3 mg/kg single dose failure diarrhea
(0.3mg/kg iv)/
isotonic saline
Ramsook ED 145 6 month GE with .5 × vomiting Ondansetron PO Vomiting episodes, Increase in 24 hrs
et al 200273 –12 years in the preceding 24 hours (syrup) 6 m – 1 year: 1.6 mg receipt of IVF, hospital diarrhea
1–3 year: 3.2 mg/ admission, and diarrheal
4–12 year: 4 mg episode
Q8H up to 6 doses
Reeves et al ED 107 1 month GE and .3 × vomiting Ondansetron IV Vomiting episodes, No 5–7 days
200272 –22 years in the preceding 24 hours, 0.15 mg/kg hospital admission, increase in
Clinical and Experimental Gastroenterology 2010:3

requiring IV Single dose duration of vomiting, diarrhea
rehydration diarrhea episodes, and
return to ED and need for
readministration of IVF
Stork ED 137 6 month GE, .3 × emesis Onsansetron/ IV Hospital admission, ORT Not assess 1 and
et al 200671 –12 years within past 24 hours, Dexamethasone 0.15 mg/kg Single dose tolerance, and degree of the 2 days
mild to moderate (1mg/kg)/ isotonic dehydration severity of
dehydration, and failed saline diarrhea
oral hydration
Freedman ED 214 6 month GE with mild to Ondansetron PO Vomiting episodes, Increase in 1–2
et al 2006(4) –10 years moderate dehydration and (orally dissolving 8–15 kg: 2 mg receipt of IVF, and diarrhea weeks
.1 × vomiting in tablet) 15–30 kg: 4 mg admission to the hospital
the preceding 4 hours .30 kg: 8 mg Single dose
Roslund ED 106 1–10 years GE with mild to Ondansetron PO Vomiting episodes, No increase 1 week
et al 200875 moderate dehydration (orally dissolving 0.15 mg/kg Single dose receipt of IVF, hospital in diarrhea
and failed oral tablet) admission, diarrheal
rehydration attempt episodes, and return visit
to ED
Yilmaz et al ED 109 5 month GE with mild to Ondansetron PO Vomiting episodes, Increase in 24 hrs
200977 –8 years moderate dehydration, (syrup) 0.2 mg/kg Q8H for 3 doses receipt of IVF, hospital diarrhea
.4 × vomiting in 6hr admission, diarrheal
and .4 × diarrhea episodes, and return visit
in 24 hours to ED
Abbreviations: GE, gastroenteritis; IV, intravenous; PO, per os; ED, emergency department; ORT, oral rehydration therapy; IVF, intravenous fluid.
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Acute gastroenteritis: from guidelines to real life
self-limiting. Furthermore, the study by Bryson, evaluating showed no significant difference in terms of efficacy.85–87
the use of ondansetron in the treatment of postoperative There has been no controlled trial directly comparing
emesis in 1900 patients, found the incidence of adverse ramosetron and ondansetron. Moreover, none of these new
events was similar to that of placebo.78 It did not cause extra- 5HT3 receptor antagonists have evaluated in the treatment
paramidal reactions or sedation.56 However, in other large of gastroenteritis related vomiting. Although one advantage
clinical trials, including some pediatric patients, documented of these medications is that their longer half-life, the main
headache as the most common adverse effect, followed by disadvantage is they are usually more expensive.
fatigue and constipation.79
Ondansetron has a good tolerability. It is completely Other antiemetic medications
and rapidly absorbed from the gastrointestinal tract, and Antihistamine
then metabolized by the cytochrome P450 enzyme system Dimenhydrinate
with subsequent glucuronide or sulfate conjugation in Dimenhydrinate is a first generation H1 receptor antagonist.
the liver.80–82 It also has a low potential for drug interac- It not only blocks the H1 receptors in the nucleus tractus
tions. Peak plasma concentration occurs approximately solitarius, it also blocks the muscarinic-cholinergic receptors
2 hours post oral and the bioavailability is approximately in both the vestibular apparatus and the vomiting center.43,82
60%. 80 Peak plasma con centration occurs 40 minutes Dimenhydrinate is very convenient to use because it can be
post intramuscular administration, and 10 minutes post given via oral, rectal, intramuscular or intravenous routes.88
intravenous administration. It has a half-life of 2 to 6 hours.81 The recommended dose is 1.25 mg/kg body weight, with a
Its antiemetic duration of action is variable from 2 to 8 hours maximum of 50 mg.43,82 It has also been used for the treatment
with standard dosing. The recommended intravenous dose and prevention of motion sickness, radiation sickness,
of ondansetron is 0.1 to 0.15 mg/kg body weight, up to a disturbances of labyrinthine function, and post operative
maximum of 4 mg.81 The recommended oral dose is 2 mg nausea and vomiting.89–92 The cost of dimenhydrinate is a
for children weighing 8 to 15 kg, 4 mg for children weighing lot less expensive when compared to ondansetron. The main
15 to 30 kg and 8 mg for children weighting .30 kg up concern for the use of dimenhydrinate in the treatment of
to a maximum of 3 times/day. However, a single dose of acute gastroenteritis related vomiting is its sedative effect.
oral ondansetron is usually sufficient for the treatment of It can jeopardize the oral intake of rehydration fluids and
gastroenteritis related vomiting. further aggravate dehydration. There have been no efficacy
The main drawback of ondansetron has been the cost; studies for dimenhydrinate in gastroenteritis until recently.
however, a generic form of ondansetron has recently been In 2009, Uhlig and colleagues published a prospective, ran-
available and so cost is no longer a barrier to its use. In domized, placebo controlled, multicenter trial investigating
addition, the use of the medication can minimize the need dimenhydrinate in children with infectious gastroenteritis.93
for hospitalization (NNT = 14) and intravenous therapy The investigators randomly assigned 243 children (aged
(NNT = 5).70 Even so there has been no formal study in terms between 6 months and 6 years) with presumed gastroenteritis
of the cost saving, although judging from the very high costs related vomiting to treatment with rectal dimenhydrinate
associated with hospitalization, the use of this medication or placebo. The dose of dimenhydrinate depended on body
may reduce the overall health care costs of treating patients weight (40 mg ,15 kg bodyweight; 80 mg for 15 to 25 kg
with gastroenteritis. bodyweight and 120 mg for bodyweights .25 kg). Additional
doses could only be given in case of visible excretion of the
Other 5HT3 receptor antagonists suppository immediately after administration or in case of
These include granisetron, tropisetron, dolasetron and persistent vomiting. Children with none or mild dehydration
ramosetron. These medications have been evaluated in the were included. All children received oral rehydration therapy.
management of post-operative and chemotherapy related A short-term follow-up visit in the study center was scheduled
nausea and vomiting. One trial comparing granisetron and at 18 to 24 hours after treatment. The investigators called
ondansetron and another comparing granisetron, tropisetron the families for a telephone interview 7 to 14 days after
and ondansetron in children undergoing chemotherapy enrollment. There was no change of bodyweight between
found no significant differences in efficacy outcomes.83,84 children who received dimenhydrinate or placebo. The mean
Three trials have compared dolasetron and ondansetron number of vomiting episodes between treatment and the
in children undergoing surgical procedures and these also follow-up visit was 0.64 in the dimenhydrinate group and
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1.36 in the placebo group. In total, 69.6% of the children occurred with all routes of administration (oral, rectal, and
in the dimenhydrinate group versus 47.4% in the placebo parenteral). Because of this, in late 2004, a “boxed warning”
group were free of vomiting between treatment and the was added to the labeling for promethazine hydrochloride
follow-up visit. The numbers needed to treat were 2 (95% (Phenergan), including a contraindication for use in children
CI: 1–4) to avoid 1 episode of vomiting and 5 (95% CI: less than two years of age and a strengthened warning with
3–12) for complete cessation of vomiting. Hospital admis- regard to the use in children two years of age or older. It
sion rate, fluid intake, general well-being of the children, should also not be prescribed to children who are already
parental satisfaction and potential adverse effects, includ- on other drugs with respiratory depressant effects as it may
ing the number of diarrheal episodes, were similar for both further aggravate the effect on respiratory depression.
groups. Sedation occurred in 21.6% children who received
dimenhydrinate and 18.6% children who received placebo. Dopamine receptor antagonists
The study showed that dimenhydrinate reduced the frequency Metoclopramide
of vomiting in children with mild dehydration; however, Metoclopramide is a chlorinated procainamide derivative
the overall benefit was low, because it did not improve oral that has been marketed since the 1960s. It acts primarily as
rehydration or clinical outcome. a D2 receptor antagonist and also has parasympathomimetic
activity with weak 5-HT3 receptor antagonist activity.88 It has
Promethazine both central and peripheral actions, and alleviates nausea and
Promethazine is derived from phenothiazines with pronounced vomiting by decreasing afferent impulses to the chemorecep-
antihistamine activity.43 It also has anti-cholinergic and anti- tor trigger zone, lowering gastric sphincter tone, stimulating
dopaminergic activities.88 Promethazine has also been used in gastric motility and accelerating gastric emptying and small
the management of post-operative nausea and vomiting and intestine transit time. It has been used for the prevention of
motion sickness.57,88 The medication is not expensive and can chemotherapy related vomiting, post-operative nausea and
also be given orally, rectally, intramuscularly or intravenously vomiting, and pregnancy associated nausea and vomiting.98
with a doses of 0.25 mg to 1 mg/kg bodyweight (up to a Two studies evaluated metoclopramide as a treatment for
maximum of 25 mg) every 4 to 6 hours as required.43 It is well vomiting associated with gastroenteritis in 96 hospitalized
absorbed orally with clinical effects beginning 20 minutes children.55,99 The first double blind, randomized, controlled
after administration. There has been only one study published, study, in 1979, was published by Van Eygen and colleagues.99
that being by Tibbs in 1968 involving 60 children that use The authors recruited 60 children aged between 2 to 6 years in
promethazine and pyrilamine-pentobarbital for the treatment an in-patient setting. The children were randomized to receive
of children with vomiting from gastroenteritis.94 However, a suppository that contained placebo (n = 20), domperidone
this study did not include a placebo group and included 30 mg (n = 20) or metoclopramide 10mg (n = 20) at study
children with a variety of illnesses other than gastroenteritis. entry repeated up to 3 times throughout the 24 hour period as
However, it showed that promethazine was less effective than clinically warranted. This study found that metoclopramide
pyrilamine-pentobarbital for the relief of vomiting. was more effective than placebo in reducing symptoms of
Since its approval in 1951, serious and often life- nausea and vomiting. No adverse events were reported.
threatening adverse events; including respiratory depression; However, a second study by Cubeddu and colleagues found
over sedation; agitation; hallucinations; seizures; and that although m etoclopramide reduced the number of
dystonic reactions have been reported with promethazine vomiting episodes the results did not reach any statistical
use in children.95,96 As of 2005, there were 38 cases of significance.55 Significantly more episodes of diarrhea were
respiratory depression, apnea, or cardiac arrest reported to reported during the first 24 hours in the metoclopramide
the Food and Drug Administration (FDA).97 Twenty two of group than the placebo group.
them were in children aged 1.5 months to 2 years of age, 7 of Metoclopramide can be given intravenously, intramuscularly
which died. Nine of these 22 patients received 1 mg or less or orally at a dose of 0.1 mg/kg (up to a maximum of 10 mg),
of promethazine per kilogram of bodyweight, plus another with the onset of action 1 to 3 minutes, 10 to 15 minutes, and 30
drug with respiratory depressant effects. A wide range of to 60 minutes, respectively.61 The half-life is 5 to 6 hours with a
weight-based doses (0.45 to 6.4 mg per kg) were associated duration of action of 1 to 2 hours.61 Reported adverse effects in
with respiratory depression. Serious outcomes, including patients who received metoclopramide included: drowsiness,
death, disability, life-threatening events, and hospitalization, cough, and tremor. Extrapyramidal reactions such as dystonia,

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akathisia and oculogyric crisis are more common in children nausea and vomiting. There have been two studies that
and reported in up to 25% of children.100,101 Extrapyramidal included 109 hospitalized children, aged between 8 months to
reactions occur regardless of the doses, (whether single or 10 years old, which examined its antiemetic effect in children
multiple doses) or routes of administration. Other severe with gastroenteritis.99,113 Unfortunately, the enrollment in
reactions such as: seizures; neuroleptic malignant syndrome; both studies was not limited to patients with gastroenteritis,
methemoglobinemia; sulfhemoglobinemia; and gynecomastia although both of them demonstrated that domperidone
have also been reported.102–104 s uppositories decreased the symptoms of nausea and
vomiting when compared with placebo. Domperidone is now
Droperidol only available for oral or suppository administration because
In June 1968 McNeil laboratories submitted a new drug cardiac arrhythmias have been reported after high intravenous
application for droperidol to the FDA. The drug was approved, dose administration; therefore, the intravenous route of
on June 11 1970, for use preoperatively, during induction and administration was discontinued.114–116 The recommended
maintenance for sedation or tranquilization, for anti-anxiety oral dose is 0.3 to 0.6 mg/kg bodyweight, with a maximum
activity, and for the reduction of the incidence of nausea and of 25 mg three times a day.82 The recommended rectal dose
vomiting. Droperidol is classified as a short acting butyrophe- is 10 mg, 30 mg and 60 mg twice/day for children age
none and a potent D2 receptor antagonist that also has weak ,2 years, 2 to 6 years and .6 years, respectively.82;99 After
anti-cholinergic and antihistamine activity.43 It is pharmaco- oral administration, peak plasma levels of domperidone occur
logically related to phenothiazines and thought to act both after 30 minutes. Peak levels after the rectal administration of
centrally and peripherally. Droperidol has been well studied suppositories is usually achieved after 1 to 2 hours. Adverse
as a postoperative antiemetic agent, but there are no studies effects of domperidone include ventricular arrhythmias and
on its efficacy in gastroenteritis related vomiting.105–107 It has a cardiac arrest.82 Unlike metoclopramide, which also has
good anti-nausea effect although a lesser antiemetic effect.108 both central and peripheral effects, domperidone does not
The recommended dose of droperidol for vomiting is 0.05 to cause any significant extrapyramidal adverse effects because
0.06 mg/kg bodyweight/dose every 4 to 6 hours intramuscularly of its poor penetration into the central nervous system.
or intravenously and the onset of action is within 3 to 10 minutes Domperidone is currently available in many countries and
with a half-life of 2 hours. Droperidol is not recommended in there is worldwide experience in the use of this agent. In the
children younger than 2 years because its safety and efficacy past 3 years, domperidone has been available in the United
have not yet been established. The side effects of droperidol are States through a compassionate clearance program.
mainly prolonged CNS depression and extrapyramidal symp-
toms. Sedative effects can last up to 12 hours.109 However, in Prochlorperazine
2001, the FDA posted a black box warning that droperidol could Prochlorperazine is a phenothiazine derivative that belongs to
cause QT prolongation and torsades de pointes. The warning the piperazine class of drugs. It is a weak dopamine receptor
was based on 273 cases reported over a 4-year period.110 Before blocker and depresses the chemoreceptor trigger zone. It
administration of droperidol, a 12-lead electrocardiogram was first introduced as an antipsychotic in the 1950s and
should be performed. Furthermore, the patient must have elec- subsequently found to be effective for controlling vomiting
trocardiographic monitoring for 2 to 3 hours after droperidol in 1956 and extended its usage in children in 1958.117 It is
administration. Manufacturers now only recommend droperidol indicated for control of severe nausea and vomiting, but not
in patients who fail to show a response to other treatments. recommended in patients less than 2 years or 9 kg. Its efficacy
Janssen Pharmaceuticals has also stopped marketing droperidol in pediatric gastroenteritis has not been documented. Even in
outside of the United States since 2001. The fallout from the adults, only 3 prospective studies are known to exist.57,118,119
black box warning has the been near cessation of droperidol These 3 studies also included vomiting from other causes.
use in the United States.111,112 The authors compared prochlorperazine to promethzine
or trimethobenzamide. All these 3 studies showed that
Domperidone prochlorperazine is more effective than promethazine or
Domperidone was first synthesized in 1974 and acts as a D2 trimethobenzamide for treating vomiting.
receptor antagonist. It acts on the chemoreceptor trigger zone However, the medication is contraindicated in patients
and it can also accelerate gastric emptying time. Domperidone with hepatic or renal dysfunction. Akathisia and dystonia are
has been used for prevention and treatment of post-operative the most common side effects in both adults and children in
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up to 44% of patients administered with this medication.57,120,121 efficacy.125 The injectable form is also contraindicated in
Children with acute illnesses such as gastroenteritis seem pediatric patients. The onset of action, following an oral dose,
more susceptible to neuromuscular reactions, particularly is within 10 to 40 minutes with a half-life 3 to 6 hours and
dystonias, than adults.(122,123) Other adverse effects include: duration of action of 3 to 4 hours. Adverse reactions include
drowsiness; depression; neuroleptic malignant syndrome; extrapyramidal reactions, drowsiness, depression, headache
orthostatic hypotension; and prolongation of the QT interval. and hypotension.
Tremor and tardive dyskinesia can occur after prolonged or
chronic use, which are usually irreversible. Dexamethasone
The recommended oral and rectal dose is 0.1 to 0.2 mg/kg Dexamethasone is a potent synthetic member of the
bodyweight with a maximum dose of 5 mg once daily to glucocorticoid class of steroid hormones. An action via its
three times daily.43 The recommended intramuscular dose is well known effects on eicosanoid metabolism, reduction
0.15 mg/kg bodyweight.43 Intravenous administration is not in inflammation and edema is probably the most favored
recommended in children. The onset of action following oral explanation for its antiemetic effects.126 It is seldom prescribed
or rectal administration is 30 to 60 minutes with a half-life as an antiemetic in acute gastroenteritis but its effective-
of 23 hours and duration of action of 3 to 4 hours. ness in chemotherapy induced emesis has been proved by
randomized controlled trial.127 However, until recently there
Unclassified antiemetics has been no randomized-controlled trial to assess it efficacy
Trimethobenzamide in treating vomiting in acute gastroenteritis. Stork and col-
Trimethobenzamide is an unclassified antiemetic medication. leagues randomized patients with acute gastroenteritis-related
Presumably, it acts on the chemoreceptor trigger zone.61 vomiting to receive: dexamethasone (47patients) 1 mg/kg
It is used for the treatment of post-operative nausea and bodyweight intravenously, (with a maximum dose of up to
vomiting. 43 Regarding its clinical efficacy for treating 15 mg); ondansetron (46 patients) 0.15 mg/kg bodyweight; or
vomiting in acute gastroenteritis in children, there are only placebo (44 patients) normal saline, 10 ml.71 Hospital admis-
2 published randomized trials. The study published by Tibbs sion occurred in nine patients (20.5%) receiving placebo (nor-
included 60 patients in a private pediatric clinic present- mal saline alone), two patients (4.4%) receiving ondansetron,
ing with vomiting due to either gastroenteritis, pharyngitis and seven patients (14.9%) receiving dexamethasone. There
or tonsillitis compared trimethobenzamide hydrochloride were no significant differences in number of mean episodes
suppositories with pyrilamine-pentobarbital suppositories.94 of vomiting or repeat visits to health care providers at 24
Another study by Ginsburg and colleagues, randomized and 72 hours in the ondansetron, dexamethasone, or normal
49 children with acute gastritis who had experienced at least saline groups. Dexamethasone was not very effective in
one episode of vomiting in the preceding 2 hours to receive a treating acute gastroenteritis related vomiting, nor effective
suppository that contained either trimethobenzamide 200 mg for reducing hospital admission in this study.
(n = 24) or placebo (n = 25).124 Both studies received low qual- The numbers of randomized controlled trials for different
ity scores and showed that trimethobenzamide was no more antiemetics, doses and routes of administration, and special
effective than placebo, and was less effective than pyrilamine considerations are summarized in Table 2.
pentobarbital in treating vomiting due to gastroenteritis.70
Bardfeld conducted a controlled double-blind study of The changing
trimethobenzamide, prochlorperazine and placebo in patients of pharmacoepidemiology
older than 17 years of age.119 The author concluded that of antiemetic medications
intramuscular prochlorperazine was more effective than In 2008, Pfeil and colleagues investigated the prescription
trimethobenzamide for the treatment of nausea and vomiting. pattern of antiemetic medications in 0 to 9-year-old children
At the same time trimethobenzamide is no more effective than with infectious gastroenteritis in several industrialized
placebo for treating vomiting in gastroenteritis. countries during 2005.63 The authors did not only look at the
The recommended dose of trimethobenzamide is 4 to percentage of antiemetic prescriptions among patients with
5 mg/kg bodyweight with a maximum of 200 mg up to 3 acute gastroenteritis, they also investigated the distribution
to 4 times/day administered orally or rectally. However, of different antiemetics among the different countries.
suppositories are contraindicated in premature or newborn Antihistamines or dopaminergic receptor antagonists were
infants and were removed from the market due to lack of prescribed preferentially in all countries. In Germany and

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Table 2 Summary of antiemetic drugs

Drug No. of Route/dose Consideration
RCT
Ondansetron 7 RCTs PO: 2 mg for BW 8–15 kg Minimal adverse effects, with good evidence
4 mg for BW 15–30 kg for reduced admission and intravenous
8 mg for BW .30 kg therapy
IV: 0.1–0.15 mg/kg BW
Dimenhydrinate 1 RCT PO/PR/IM/IV: 1.25 mg/kg BW Sedative effect
Promethazine 1 RCT PO/PR/IM/IV: 0.25-1 mg/kg BW FDA black box warning
Metoclopramide 2 RCTs PO/IM/IV: 0.1 mg/kg BW High frequency of extra-pyramidal reaction
Droperidol No RCT IM/IV: 0.05–0.06 mg/kg BW FDA black box warning
Domperidone 2 RCTs PO: 0.3–0.6 mg/kg BW No IV as increase cardiac arrhythmias
PR: ,2 yr: 10 mg, 2–6yr:
30 mg, .6 yr: 60 mg
Prochlorperazine No RCT PO: 0.1–0.2 mg/kg BW Not recommended if ,2y/IV dosing not
PR: 0.1–0.2 mg/kg BW recommended in pediatric patients
IM: 0.15 mg/kg BW
Trimethobenzamide 2 RCTs PO: 4–5 mg/kg BW PR form was removed from the
PR: 4–5 mg/kg BW manufacture/IM/IV routes not
recommended in pediatric patients
Abbreviations: BW, body weight; PO, per os; PR, per rectum; IM, intramuscular; IV, intravenous; FDA, Food and Drug Administration; RCT, randomized controlled trial.
Canada, dimenhydrinate accounted most of the prescrip- those presenting to emergency departments and those seek-
tions. In the United States, promethazine was the most ing outpatient care for acute gastritis received ondansetron.
commonly prescribed antiemetic, even though the FDA had However, the percentage had grown to 3.43% in emergency
issued a black box warning. The dopamine receptor antago- departments and 3.6% in outpatient care during 2008. After
nist domperidone was preferred in Spain, France, Italy and the availability of a generic formula of this drug it is antici-
United Kingdom. The prescription rate of ondansetron was pated that the use of ondansetron will most likely increase.
0% in Germany, Canada, Spain and Italy, 3% in United Status
and 6% in United Kingdom. It seems that there is a strong The essential pillars of good
variation among the different countries in the prescription treatment of acute gastroenteritis
pattern. The serotonin receptor antagonist ondansetron was Oral rehydration therapy is still the key treatment for
prescribed in a small number of patients only. Cost was a bar- acute gastroenteritis. Many physicians still believe that
rier because as there was no generic form available at the time. antiemetic medications have no role in the management
Furthermore, the proof of therapeutic efficacy of ondansetron of acute ga stroenteritis. However, after reviewing the
is relatively new. Physicians are just beginning to adopt the existing literature, it is evident that ondansetron decreases
use of ondansetron as a strategy for avoiding intravenous the fr equency of vomiting, improves the success and
therapy and hospitalization for children with gastroenteritis compliance of oral rehydration therapy and decreases the
related vomiting. In 2009, the use of antiemetics in children rate of intravenous therapy. It can also decrease the rate of
between the ages of 1 and 10 years in emergency visits, hospitalization. Even though there is no formal economic
reported to the National Ambulatory Medical Care Survey study, judging from the high cost of hospitalization and the
database, from 2002 to 2006 was published.128 The database decreasing cost of the medication, it is likely that ondansetron
included more than 3 million pediatric visits per year to can reduce the health care costs in patients presenting with
emergency departments for acute gastroenteritis. The study acute gastroenteritis. When compared to placebo ondansetron
showed the rate of prescribed ondansetron increased from does not increase revisited rate. It has a very good safety
0.53% in 2002 to 6.42% in 2006. A similar analysis of both profile and does not have a sedative effect. The only drawback
emergency department and outpatient visits to academic is the increased frequency of diarrhea after its usage; however
medical centers and teaching hospitals from 2005 through to this is usually transient and well tolerated. Although there is
2008, derived from the University Health System Consortium no study to evaluate parental satisfaction the success of oral
Clinical Database, showed a similar trend.128 Only 0.5% of rehydration therapy always means that the patients can be
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managed at home; which is more comfortable for both the 6. Carlin JB, Chondros P, Masendycz P, Bugg H, Bishop RF, Barnes
GL. Rotavirus infection and rates of hospitalisation for acute
patients and parents. As vomiting usually lasts for a few days gastroenteritis in young children in Australia, 1993–1996. Med J Aust.
one dose of ondansetron is usually enough. An oral dose is 1998;169(5):252–256.
preferred because it can be easily given and can avoid the 7. Fang ZY, Yang H, Zhang J, et al. Child rotavirus infection in association
with acute gastroenteritis in two Chinese sentinel hospitals. Pediatr Int.
setting of an intravenous drip, which may be quite painful 2000;42(4):401–405.
to the patients. 8. Canadian Paediatric Society. Oral rehydration therapy and early refeed-
ing in the management of childhood gastroenteritis. Paediatr Child
In 2008, the European Society for Pediatric Health. 2006;11(8):527–531.
G astroenterology, Hepatology, and Nutrition and the 9. Nelson EA, Tam JS, Bresee JS, et al. Estimates of rotavirus disease bur-
European Society for Pediatric Infectious Diseases published den in Hong Kong: hospital-based surveillance. J Infect Dis 2005;(192
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an evidence-based guideline for the management of acute 10. Webb A, Starr M. Acute gastroenteritis in children. Aust Fam Physician.
gastroenteritis in children in Europe.129 The statement has 2005;34(4):227–231.
11. Wilhelmi I, Roman E, Sanchez-Fauquier A. Viruses causing
changed the perspective on antiemetics and comments that gastroenteritis. Clin Microbiol Infect. 2003;9(4):247–262.
antiemetics may be of value for selected children with severe 12. Rivest P, Proulx M, Lonergan G, Lebel MH, Bedard L.
vomiting. However, the guideline does not clearly state the Hospitalisations for gastroenteritis: the role of rotavirus. Vaccine.
2004;22(15–16):2013–2017.
indications and rationales for choosing the different kinds 13. Ehlken B, Laubereau B, Karmaus W, Petersen G, Rohwedder A, Forster
of antiemetics. In the future, guidelines should concentrate J. Prospective population-based study on rotavirus disease in Germany.
Acta Paediatr. 2002;91(7):769–775.
more on the subgroup of patients that can benefit from the 14. Parashar UD, Hummelman EG, Bresee JS, Miller MA, Glass RI. Global
antiemetics, and which antiemetics could provide the best illness and deaths caused by rotavirus disease in children. Emerg Infect
clinical advantages. Dis. 2003;9(5):565–572.
15. Parashar UD, Gibson CJ, Bresse JS, Glass RI. Rotavirus and severe
The essential pillars of good treatment of acute childhood diarrhea. Emerg Infect Dis. 2006;12(2):304–6.
gastroenteritis always include the followings:130 16. Leung AK, Kellner JD, Davies HD. Rotavirus gastroenteritis. Adv Ther.
2005;22(5):476–487.
i. Use of oral rehydration for dehydration; 17. Andreasi MS, Cardoso DD, Fernandes SM, et al. Adenovirus, calicivirus
ii. Hypotonic oral rehydration solution; and astrovirus detection in fecal samples of hospitalized children
iii. Fast oral rehydration over 3 to 4 hours; with acute gastroenteritis from Campo Grande, MS, Brazil. Mem Inst
Oswaldo Cruz. 2008;103(7):741–744.
iv. Rapid realimentation with normal feeding; 18. Caracciolo S, Minini C, Colombrita D, Foresti I, Avolio M, Tosti G,
v. Use of special formula is unjustified; et al. Detection of sporadic cases of Norovirus infection in hospitalized
children in Italy. New Microbiol. 2007;30(1):49–52.
vi. Use of diluted formula is unjustified; 19. Fodha I, Chouikha A, Dewar J, Trabelsi A, Boujaafar N, Steele AD.
vii. Continuation of breast feeding at all time; Prevalence of adenovirus antigens in children presenting with acute
viii. Supplement with oral rehydration solution for ongoing diarrhoea. Med Trop (Mars). 2007;67(3):256–258.
20. Jakab F, Peterfai J, Meleg E, Banyai K, Mitchell DK, Szucs G.
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35–40.
Disclosure 23. Parashar UD, Alexander JP, Glass RI. Prevention of rotavirus
The authors report no conflicts of interest relevant to this gastroenteritis among infants and children. Recommendations of the
Advisory Committee on Immunization Practices (ACIP). MMWR
research.
Recomm Rep. 2006;55(RR-12):1–13.
24. Malek MA, Curns AT, Holman RC, et al. Diarrhea- and rotavirus-
associated hospitalizations among children less than 5 years of
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