You are in: eMedicine Specialties > Emergency Medicine > PEDIATRIC Pediatrics, GastroenteritisArticle Last Updated: Jun 16, 2008AUTHOR AND EDITOR INFORMATIONAuthor: Adam Levine, MD, MPH, Resident Physician, Department of Emergency Medicine, Brigham and Women's Hospital Adam Levine is a member of the following medical societies: Emergency Medicine Residents Association Coauthor(s): Karen A Santucci, MD, Fellowship Director of Pediatric Emergency Medicine, Department of Pediatrics, Assistant Professor, New Haven Children's Hospital, Yale University Editors: James Li, MD, Former Assistant Professor, Division of Emergency Medicine, Harvard Medical School; Board of Directors, Remote Medicine; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Wayne Wolfram, MD, MPH, Clinical Associate Professor, Departments of Pediatrics, Children's Hospital and University of Cincinnati; John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; Richard G Bachur, MD, Assistant Professor of Pediatrics, Harvard Medical School; Associate Chief and Fellowship Director, Attending Physician, Division of Emergency Medicine, Children's Hospital of Boston Author and Editor Disclosure Synonyms and related keywords: acute gastroenteritis, diarrhea, dysentery, gastroenteritis in children, gastroenteritis in infants, vomiting, dehydration, gastroesophageal reflux disease, GERD, gastric outlet, pyloric stenosis, intestinal obstruction, hernia, intussusception, diabetic ketoacidosis, urinary tract infection, pyelonephritis, enteric adenovirus, norovirus, rotavirus, Campylobacter, Salmonella, Shigella, enterohemorrhagic Escherichia coli, EHEC, enterotoxigenic E coli, ETEC, cholera, parasitic gastroenteritis INTRODUCTIONBackgroundAlthough often considered a benign disease, acute gastroenteritis remains a major cause of morbidity and mortality in children around the world, accounting for 1.8 million deaths annually in children younger than 5 years, or roughly 17% of all child deaths. Because the severity of the disease can widely vary depending on the volume of fluid loss, accurately assessing and treating dehydration in children presenting with acute gastroenteritis remains a critical skill for every emergency physician. Luckily, most cases of dehydration in children can be accurately diagnosed by a careful clinical examination and treated with simple, cost-effective measures. PathophysiologyAdequate fluid balance in humans depends on the secretion and reabsorption of fluid and electrolytes in the intestinal tract; diarrhea occurs when intestinal fluid output overwhelms the absorptive capacity of the GI tract. The primary mechanisms responsible for acute gastroenteritis are (1) damage to the villous brush border of the intestine, causing malabsorption of intestinal contents and leading to an osmotic diarrhea, and (2) the release of toxins that bind to specific enterocyte receptors and cause the release of chloride ions into the intestinal lumen, leading to secretory diarrhea. Even in severe diarrhea, various Na-coupled solute cotransport mechanisms remain intact, allowing for the efficient reabsorption of salt and water. By providing a 1:1 proportion of Na to glucose, classic oral rehydration solution (ORS) takes advantage of a specific Na-glucose transporter (SGLT-1) to increase the reabsorption of Na, which leads to the passive reabsorption of water. Alternatively, rice- and cereal-based ORS take advantage of Na-amino acid transporters to increase reabsorption of fluid and electrolytes. FrequencyUnited StatesIn the United States, acute gastroenteritis remains a major cause of morbidity in children, accounting for more than 1.5 million outpatient visits, 200,000 hospitalizations, and 300 deaths each year. InternationalWorldwide, children younger than 5 years suffer from an estimated 1.4 billion episodes of diarrhea each year, leading to 123 million clinic visits, 9 million hospitalizations, and 1.8 million deaths. Although the absolute number of cases of acute gastroenteritis has changed little over the past 4 decades, the mortality has declined sharply, from 4.6 million in the 1970s to 3 million in the 1980s to 2.5 million in the 1990s. One of the most important reasons for this decline has been the increasing international support for the use of ORS as the treatment of choice for acute diarrhea, with the proportion of diarrheal episodes treated with ORS rising from 15% in 1984 to 40% in 1993. CLINICALHistoryThe history helps both in differentiating gastroenteritis from other, often more serious, causes of vomiting and diarrhea in children, and in estimating the degree of dehydration. In some cases, the history can also aid in determining the type of pathogen responsible for the gastroenteritis, though only rarely will this effect management.
PhysicalThe physical examination should confirm and clarify the assessment of dehydration and should narrow diagnostic possibilities generated by the history.
CausesIdentifying the specific etiologic agent responsible for the acute gastroenteritis rarely changes management. However, it may be helpful to differentiate between viral, bacterial, parasitic, and noninfectious causes of diarrhea.
DIFFERENTIALSDiabetic Ketoacidosis Gastritis and Peptic Ulcer Disease Giardiasis Hemolytic Uremic Syndrome Hepatitis Inflammatory Bowel Disease Pancreatitis Pediatrics, Appendicitis Pediatrics, Foreign Body Ingestion Pediatrics, Intussusception Pediatrics, Pyloric Stenosis Pediatrics, Urinary Tract Infections and Pyelonephritis Shock, Septic
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| Variable | Mild (3-5%) | Moderate (6-9%) | Severe (³10%) |
| Blood pressure | Normal | Normal | Normal to reduced |
| Quality of pulses | Normal | Slightly diminished | Moderately diminished |
| Heart rate | Normal | Increased | Increased |
| Skin turgor | Normal | Decreased | Decreased |
| Fontanelle | Normal | Sunken | Sunken |
| Mucous membranes | Slightly dry | Dry | Dry |
| Eyes | Normal | Sunken orbits | Deeply sunken orbits |
| Extremities | Normal cap refill | Delayed cap refill | Cool, mottled |
| Mental status | Normal | Listless | Lethargic, comatose |
| Urine output | Slightly decreased | <1 mL/kg/h | ³1 mL/kg/h |
| Thirst | Slightly decreased | Moderately increased | Too lethargic to indicate |
| Severe dehydration | Two of the following signs: • Lethargic or unconscious • Sunken eyes • Not able to drink or drinking poorly • Skin pinch goes back very slowly |
| Some dehydration | Two of the following signs: • Restless, irritable • Sunken eyes • Thirsty, drinks eagerly • Skin pinch goes back slowly |
| No dehydration | Not enough of the above signs to classify as some or severe dehydration |
The AAP, the European Society of Pediatric Gastroenterology and Nutrition (ESPGAN), and the WHO all recommend ORS as the treatment of choice for children with mild-to-moderate gastroenteritis in both developed and developing countries, based on the results of dozens of randomized, controlled trials and several large meta-analyses. One large meta-analysis of 16 trials including 1545 children with mild-to-moderate dehydration found that, compared with intravenous rehydration, children treated with ORS had a significant reduction in length of hospital stay and fewer adverse events, including seizures and death.4 In most large trials, the rate of ORS failure (percentage of children eventually requiring intravenous hydration) was about 4%.
The goals of pharmacotherapy are to reduce morbidity, prevent complications, and prophylaxis. Antidiarrheal (ie, kaolin-pectin) and antimotility agents (ie, loperamide) are contraindicated in the treatment of acute gastroenteritis in children because of their lack of benefit and increased risk of side effects, including ileus, drowsiness, and nausea.
Probiotics are live microbial feeding supplements commonly used in the treatment and prevention of acute diarrhea. Possible mechanisms of action include synthesis of antimicrobial substances, competition with pathogens for nutrients, modification of toxins, and stimulation of nonspecific immune responses to pathogens. Several large studies and two recent meta-analyses have found probiotics (especially Lactobacillus GG) to be effective in reducing the duration of diarrhea in children presenting with acute gastroenteritis.8
Several large studies, all conducted in developing countries, have shown zinc supplementation to be effective in reducing the duration and severity of diarrhea in children with acute gastroenteritis, as well as the likelihood of recurrence of diarrhea.9 The WHO recommends zinc supplementation (10-20 mg/d for 10-14 d) for all children younger than 5 years with acute gastroenteritis, although little data support this recommendation for children in developed countries.
In February 2006, the US Food and Drug Administration (FDA) approved the RotaTeq vaccine for prevention of rotavirus gastroenteritis. The vaccine has been endorsed by the AAP and is currently the only available vaccine for the prevention of viral gastroenteritis in infants and children.
In April 2008, the FDA approved Rotarix, another oral vaccine, for prevention of rotavirus gastroenteritis. The current recommendation is to administer 2 separate doses of Rotarix to patients aged 6-24 weeks. Rotarix was efficacious in a large study, which reported that Rotarix protected patients with severe rotavirus gastroenteritis and decreased the rate of severe diarrhea or gastroenteritis of any cause.10
| Drug Name | Rotavirus vaccine (RotaTeq, Rotarix) |
|---|---|
| Description | Currently, 2 orally administered live-virus vaccines are marketed in the United States. Each is indicated to prevent rotavirus gastroenteritis, a major cause of severe diarrhea in infants. RotaTeq is a pentavalent vaccine that contains 5 live reassortant rotaviruses and is administered as a 3-dose regimen against G1, G2, G3, and G4 serotypes, the 4 most common rotavirus group A serotypes. It also contains attachment protein P1A (genotype P[8]). Rotarix protects against rotavirus gastroenteritis caused by G1, G3, G4, and G9 strains and is administered as a 2-dose series in infants aged 6-24 wk. Clinical trials reported that the vaccines prevented 74-78% of all rotavirus gastroenteritis cases, nearly all severe rotavirus gastroenteritis cases, and nearly all hospitalizations due to rotavirus. |
| Adult Dose | Not indicated |
| Pediatric Dose | <6 weeks: Not established RotaTeq 6-12 weeks: 2 mL PO as a single dose, followed by 2 additional doses at 4- to 10-wk intervals; do not administer after age 32 wk Rotarix 6 weeks: 1 mL PO as a single dose; administer a second dose after an interval of at least 4 wk and before age 24 wk |
| Contraindications | Documented hypersensitivity; uncorrected congenital GI malformation that would predispose to intussusception |
| Interactions | Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, high-dose corticosteroids) may decrease immune response |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Common adverse effects include diarrhea, vomiting, otitis media, inflamed nasal passages, and bronchospasm; refrigerate and protect from light; handle and discard empty tube according to biological waste procedures; previously marketed rotavirus vaccine (RotaShield) was associated with intussusception; however, RotaTeq did not show an increased risk compared with placebo in clinical trials (monitor for signs of intestinal blockage), and Rotarix did not show an increase in intussusception in 31,673 infants compared with 31,552 infants who received placebo; do not mix in same syringe with other vaccines or solutions |
Since the majority of cases of acute gastroenteritis in developed and developing countries are due to viruses, antibiotics are generally not indicated. Even in cases (eg, dysentery) where a bacterial pathogen is suspected, antibiotics may be ineffective (Campylobacter), may prolong the carrier state (Salmonella), or may increase the risk of hemolytic uremic syndrome (enterohemorrhagic E coli).
In patients with positive stool assays or high clinical suspicion for C difficile, the offending antibiotic should be stopped immediately. Metronidazole (30 mg/kg/d divided qid for 7 d) can be used as a first-line agent, with oral vancomycin reserved for resistant infections.
Although generally not recommended for children younger than 8 years, tetracycline (50 mg/kg/d divided qid for 3 d) and doxycycline (6 mg/kg single dose) remain the treatment of choice for cholera. Alternative treatments with good efficacy include erythromycin and ciprofloxacin.
For patients with ova and parasites (O+P) confirming infection with Giardia, metronidazole (35-50 mg/kg/d divided q8h) remains the drug of choice. Nitazoxanide oral suspension (age 1-3: 100 mg q12h for 3 d, age 4-11: 200 mg q12h for 3 d) is as effective as metronidazole and has the added benefit of treating other intestinal parasites, such as Cryptosporidium.
| Drug Name | Metronidazole (Flagyl) |
|---|---|
| Description | Recommended as the treatment of choice for mild-to-moderate cases of C difficile colitis. Provides effective therapy, with reported response rates from 95-100%. In vitro activity is bactericidal and dose dependent. Standard dosing has been shown to promote fecal concentrations capable of a 99.99% reduction of C difficile. Metronidazole IV may be administered to those patients who cannot tolerate PO medications because of its potential to accumulate in the inflamed colon. IV route is not as effective as PO. |
| Pediatric Dose | 30 mg/kg/d PO divided qid for 7 d |
| Contraindications | Documented hypersensitivity |
| Interactions | May increase toxicity of anticoagulants, cyclosporine, lithium, phenytoin, tacrolimus, and carbamazepine; cimetidine may increase toxicity of metronidazole; disulfiram reaction may occur with orally ingested ethanol; coadministration increases amiodarone toxicity (QT prolongation); increases disulfiram toxicity (psychotic symptoms) with concurrent use; phenobarbital and rifampin may increase metabolism of metronidazole |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Caution with liver impairment, blood dyscrasias, CNS disease; reduce dosage with severe hepatic disease; monitor for seizures and development of peripheral neuropathy |
| Drug Name | Nitazoxanide (Alinia) |
|---|---|
| Description | Inhibits growth of C parvum sporozoites and oocysts and G lamblia trophozoites. Elicits antiprotozoal activity by interference with the pyruvate: ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction, which is essential to anaerobic energy metabolism. Available as an oral suspension (20 mg/mL). |
| Pediatric Dose | <1 year: Not established 1-3 years: 100 mg (5 mL) PO q12h for 3 d with food 4-12 years: 200 mg (10 mL) PO q12h for 3 d with food >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Tizoxanide (nitazoxanide metabolite) is >99.9% bound to plasma protein and may potentially increase toxicity of other highly plasma protein-bound drugs |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | May cause abdominal pain, diarrhea, vomiting, or headache; administer with food; caution when coadministered with other highly plasma protein-bound drugs with narrow therapeutic indices. |
A recent large, prospective, randomized, double-blind trial compared a single dose of an orally disintegrating ondansetron tablet to placebo in children presenting to an emergency department with acute gastroenteritis. The study found that children treated with ondansetron were less likely to vomit, had greater oral intake, were less likely to require intravenous rehydration, and had a reduced length of stay in the emergency department compared with children treated with placebo. Previous smaller studies have shown ondansetron to be similarly effective in children, although little data exist regarding the efficacy of other antiemetic drugs.
| Drug Name | Ondansetron (Zofran) |
|---|---|
| Description | Selective 5-HT3-receptor antagonist that blocks serotonin both peripherally and centrally. |
| Pediatric Dose | <8 kg: Not established 8-15 kg: 2 mg PO once 15-30 kg: 4 mg PO once >30 kg: 8 mg PO once |
| Contraindications | Documented hypersensitivity |
| Interactions | Although potential for cytochrome P-450 inducers (barbiturates, rifampin, carbamazepine, and phenytoin) to change half-life and clearance of ondansetron, dosage adjustment is not usually required |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | May cause headache |
The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, David W Marby, MD† , to the development and writing of this article.
Pediatrics, Gastroenteritis excerpt
Article Last Updated: Jun 16, 2008