Ondansetron and Oral Rehydration Therapy in Pediatric Patients with Dehydration: A Review of Clinical Effectiveness [Internet]

Dehydration occurs when losses of water and electrolytes are not adequately replaced,, often secondary to vomiting and diarrhea related to gastroenteritis. Severe dehydration and the resultant decreased blood volume results in decreased tissue perfusion and can cause ischemic end-organ damage if not corrected with fluid repletion. Oral rehydration solution was an important medical advance, resulting in decreased mortality from diarrheal illness.Several methods of defining and categorizing severity of dehydration have been used in the literature. The World Health Organization (WHO) categorizes dehydration as severe dehydration (two or more signs of severe dehydration), some dehydration (two or more signs of dehydration that are not severe), or no dehydration (not meeting the criteria for some or severe). The Clinical Dehydration Scale is a validated four-item scale categorizing dehydration as mild, moderate or severe according to physical exam findings; the clinical features assessed are appearance, eyes, mucous membranes, and tears. A score between 1 and 4 is considered mild dehydration, whereas a score of 5 to 8 is considered moderate to severe. Dehydration can also be categorized according to percentage of body weight lost; mild dehydration corresponds to a loss of 3% to 5% of body weight, moderate 6% to 9%, and severe 10% or greater.,Oral rehydration therapy refers to the frequent administration of small amounts of fluid in order to prevent or treat dehydration. The oral rehydration solution recommended by the WHO contains 75 mEq/L of sodium and 75 mmol/L of glucose, with a total osmolarity of 245 mOsm/L. For severe dehydration, WHO recommends intravenous administration of isotonic fluid as well as oral rehydration therapy with oral rehydration solution if feasible. Oral rehydration therapy (with oral rehydration solution) is recommended for children with some dehydration. Administration of extra oral fluids at home is recommended for children with no dehydration. A number of antiemetics have been studied in children with gastroenteritis, including dexamethasone, dimenhydrinate, domperidone, granisetron, metoclopramide, and ondansetron. Apart from ondansetron, evidence to support the use of other antiemetics in children with acute gastroenteritis is lacking.,Ondansetron is a serotonin receptor antagonist, selective for the 5-HT3 subtype. It is indicated for the prevention and treatment of nausea and vomiting related to chemotherapy or radiotherapy, as well as post-operative nausea and vomiting, in children age 4-18 and adults. Ondansetron is available in Canada as an oral solution, tablet, and oral disintegrating tablet (ODT). It is typically well-tolerated; the most common adverse effects include mild headache, asthenia, constipation, and dizziness., Although, an increased risk of diarrhea up to 48 hours after administration of ondansetron was the most commonly reported adverse effect in studies of children with gastroenteritis. Ondansetron causes dose-dependent prolongation of the QT-interval, and cases of torsades de pointes have been reported. Ondansetron should be avoided in patients with congenital long QT syndrome and used with caution in individuals at risk of torsades de pointes.The Canadian pediatric society recommends considering a single dose of ondansetron for children between 6 months to 12 years old presenting to the emergency department with vomiting related to suspected acute gastroenteritis, and mild to moderate dehydration or failed oral rehydration therapy. They recommend initiation of oral rehydration therapy 15 min to 30 min after administration of oral ondansetron.The objective of this review was to summarize the evidence surrounding the clinical effectiveness of ondansetron for pediatric patients with or at risk of mild to moderate dehydration. For the purposes of this report, dehydration is categorized as mild to moderate according to the definitions used within the included studies. The population considered to be “at risk” of dehydration includes those who do not meet the criteria for mild or moderate dehydration according to the study definition but in whom oral rehydration therapy is deemed necessary.

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