Though often considered a benign disease, acute gastroenteritis remains a leading cause of pediatric morbidity and mortality around the world, accounting for 533,800 deaths annually in children younger than 5 years (higher than other well-known diseases such as malaria, HIV & TB for the same age group).[1] See the video below.
View Video
Child with sunken eyes.
Viruses remain by far the most common cause of acute gastroenteritis in children, both in high-resource and low-resource settings, though several bacterial species also play an important role in acute gastroenteritis, especially in low-resource settings. The two primary mechanisms responsible for acute gastroenteritis are as follows:
Damage to the villous brush border of the intestine, causing malabsorption of intestinal contents and leading to osmotic diarrhea
Toxins that bind to specific enterocyte receptors and cause the release of chloride ions into the intestinal lumen, leading to secretory diarrhea
Signs and symptoms
These include the following:
Diarrhea
Vomiting
Increase or decrease in urinary frequency
Abdominal pain
Signs and symptoms of infection - Presence of fever, chills, myalgias, rash, rhinorrhea, sore throat, cough; these may be evidence of systemic infection or sepsis
Changes in appearance and behavior - Including weight loss and increased malaise, lethargy, or irritability, as well as changes in the amount and frequency of feeding and in the child’s level of thirst
History of recent antibiotic use - Increases the likelihood of Clostridium difficile
History of travel to endemic areas
Assessment of dehydration
According to the World Health Organization (WHO), a patient exhibiting 2 of the following signs can be considered to have some amount of dehydration:
Restless, irritable
Sunken eyes
Thirsty, drinks eagerly
Skin pinch goes back slowly
According to the WHO, a patient exhibiting 2 of the following signs can be considered to have severe dehydration:
Lethargic or unconscious
Sunken eyes
Not able to drink or drinking poorly
Skin pinch goes back very slowly
See Clinical Presentation for more detail.
Diagnosis
Workup in pediatric gastroenteritis can include the following:
Baseline electrolytes, bicarbonate, and urea/creatinine - In any child being treated with intravenous fluids for severe dehydration
Fecal leukocytes and stool culture - May be helpful in children presenting with dysentery
Stool analysis for C difficile toxins - In children older than 12 months with a recent history of antibiotic use
Stool analysis for ova and parasites - In patients with a history of prolonged watery diarrhea (>14 days) or travel to an endemic area
Complete blood count (CBC) and blood cultures - Any child with evidence of systemic infection
If indicated, urine cultures, chest radiography, and/or lumbar puncture should be performed. Several studies have found that combinations of clinical signs and symptoms may have better sensitivity and specificity for detecting dehydration in children than do individual signs or symptoms.[2, 3, 4, 5, 6]
See Workup for more detail.
Management
Oral rehydration solution
The American Academy of Pediatrics, the European Society of Pediatric Gastroenterology and Nutrition (ESPGAN), and the World Health Organization (WHO) all recommend oral rehydration solution (ORS) as the treatment of choice for children with mild to moderate gastroenteritis, including those in both high-resource and low-resource settings, based on the results of dozens of randomized, controlled trials and several large meta-analyses.[7, 8, 9]
Pharmacologic therapy
Agents used in the treatment or prevention of acute pediatric gastroenteritis include the following:
Probiotics - As probiotic preparations vary widely, it is difficult to estimate the effectiveness of any single preparation. Evidence is mixed for the effectiveness of some probiotics.
Zinc - To treat diarrhea;[10] the WHO and two systematic reviews support (with moderate evidence) zinc supplementation for all children younger than 5 years with acute gastroenteritis in low-resource settings, though little data exist to support this recommendation for children in high-resource settings
Metronidazole and Tinidazole - first-line drugs- In patients infected with C difficile and Giardia
Tetracycline and doxycycline - For cholera (azithromycin should be used for children younger than 8 years)
Vaccine - In February 2006, the US Food and Drug Administration (FDA) approved the RotaTeq vaccine for prevention of rotavirus gastroenteritis
Though often considered a benign disease, acute gastroenteritis remains a leading cause of morbidity and mortality in children around the world, accounting for 533,800 deaths annually in children younger than 5 years.[1] Because the disease severity depends on the degree of fluid loss, accurately assessing dehydration status remains a crucial step in preventing mortality. Luckily, most cases of dehydration in children can be accurately diagnosed by a careful clinical examination and treated with simple, cost-effective measures.
See the video below depicting a child with acute gastroenteritis.
Adequate 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 gastrointestinal tract. The 2 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.[6]
However, even in severe diarrhea, various sodium-coupled solute co-transport mechanisms remain intact, allowing for the efficient reabsorption of salt and water. By providing a 1:1 proportion of sodium to glucose, classic oral rehydration solution (ORS) takes advantage of a specific sodium-glucose transporter (SGLT-1) to increase the reabsorption of sodium, which leads to the passive reabsorption of water. Rice- and cereal-based ORS may also take advantage of sodium-amino acid transporters to increase reabsorption of fluid and electrolytes.[6]
In the US, diarrheal diseases were the only cause of infectious diseases mortality to increase from 2000 to 2014, reaching a rate of 2.41 deaths per 100 000 persons.[11]
International
An estimated of 1.1 billion episodes of diarrhea (1.8 episodes per child) occurs in children younger than 5 years old in 2016.[12] Diarrhea is the ninth leading cause of death worldwide (1.3 million deaths per year) and the fourth leading cause among children under 5 (or approximately 40% of deaths). Rotavirus is the leading cause of diarrhea deaths, follow by Cryptosporidium spp, and Shigella spp.[13] Globally, norovirus costs society $39.8 billion among children less than 5 years of age and poses a considerable economic exceed that of rotavirus.[14]
Research has shown that early daycare attendence may be a risk factor for AGE in infants, but also protective against AGE later in childhood. One study found that first-year daycare attendance advances the timing of acute gastroenteritis infections, resulting in increased acute gastroenteritis disease burden in the first year of life and relative protection thereafter. The study also added that protection against acute gastroenteritis infection persists at least up to age 6 years.[15]
Most cases of AGE follow a relatively benign course, with less than 2% of diarrheal episodes progressing to severe disease. Even among children who develop severe diarrhea, mortality is only about 2%.[16] Younger children under two years of age tend to be at higher risk of death.[16] In all cases, early and appropriate rehydration can reduce mortality in both high and low-resource settings.
Parents should be reassured that AGE is generally a benign disease, and in most cases will improve on its own within one week without specific treatment. For children without signs of dehydration who are being discharged home, parents should be told to continue breastfeeding/general feeding of the child, and can encourage extra fluid intake as long as the child tolerates. Parents should be told to return if their child develops intractable vomiting, signs of more severe dehydration such as irritablity or lethargy, sunken eyes, reduced skin pinch, decreased tears, or refusal to drink fluids. Parents should also be told to return if the child develops high fevers, seizures, worsening abdominal pain, or bloody diarrhea, or if the diarrhea continues to persist beyond 1-2 weeks.
The history and physical examination serve two vital functions: (1) differentiating gastroenteritis from other causes of vomiting and diarrhea in children, and (2) estimating the degree of dehydration. In some cases, the history and physical examination can also aid in determining the type of pathogen responsible for the gastroenteritis, though only rarely will this affect management.
Diarrhea: Duration of diarrhea, the frequency and amount of stools, the time since last episode of diarrhea, and the quality of stools. Frequent, watery stools are more consistent with viral gastroenteritis, whereas stools with blood or mucus are indicative of a bacterial pathogen, and "rice water" diarrhea is typically associated with cholera. Similarly, a long duration of diarrhea (>14 d) is more consistent with a parasitic or noninfectious cause of diarrhea. It is important to note that the WHO definition of diarrhea is 3 or more loose stools per day.
Vomiting: Duration of vomiting, the amount and quality of vomitus (eg, food contents, blood, bile), and time since the last episode of vomiting. When symptoms of vomiting predominate, one should consider other diseases such as gastroesophageal reflux disease (GERD), diabetic ketoacidosis, pyloric stenosis, acute abdomen, or urinary tract infection.
Urination: Increase or decrease in frequency of urination measured by number of wet diapers, time since last urination, color and concentration of urine, and presence of dysuria. Urine output may be difficult to determine with frequent watery stools.
Abdominal pain: Location, quality, radiation, severity, and timing of pain, per report of parents and/or child. In general, pain that precedes vomiting and diarrhea is more likely to be due to abdominal pathology other than gastroenteritis.
Signs of infection: Presence of fever, chills, myalgias, rash, rhinorrhea, sore throat, cough, known immunocompromised status. These may indicate evidence of systemic infection or sepsis.
Appearance and behavior: Weight loss, quality of feeding, amount and frequency of feeding, level of thirst, level of alertness, increased malaise, lethargy, or irritability, quality of crying, and presence or absence of tears with crying.
Antibiotics: History of recent antibiotic use increases the likelihood of Clostridium difficile.
Travel: History of travel to endemic areas may make prompt consideration of organisms that are relatively rare in the United States, such as parasitic diseases or cholera.
General: Weight, ill appearance, level of alertness, lethargy, irritability as depicted in the video below.
View Video
Child with lethargy/poor general appearance.
Head, ears, eyes, nose, and throat (HEENT): Presence or absence of tears, dry or moist mucous membranes, and whether the eyes appear sunken as shown in the videos below.
View Video
Child with absent tears.
View Video
Child with sunken eyes.
Cardiovascular: Heart rate and quality of pulses
Respiratory: Rate and quality of respirations (The presence of deep, acidotic breathing suggests severe dehydration.). See the video below.
View Video
Child with hyperpnea (deep, acidotic breathing)
Abdomen: Abdominal tenderness, guarding, and rebound, bowel sounds. Abdominal tenderness on examination, with or without guarding, should prompt consideration of diseases other than gastroenteritis.
Back: Flank/costovertebral angle (CVA) tenderness increases the likelihood of pyelonephritis.
Rectal: Quality and color of stool, presence of gross blood or mucus
Extremities: Capillary refill time, warm or cool extremities
Skin: Abdominal rash may indicate typhoid fever (infection with Salmonella typhi), whereas jaundice might make viral or toxic hepatitis more likely. The slow return of abdominal skin pinch suggests decreased skin turgor and dehydration (see the video below), while a doughy feel to the skin may indicate hypernatremia.
Identifying 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.
By far, viruses remain the most common cause of acute gastroenteritis in children, both in high-resource and low-resource settings. In the United States, routine rotavirus vaccination has led to a 60-75% reduction in pediatric rotavirus hospitalization since 2006.[17] Rotavirus infection follows seasonal variation, with an increased incidence in winter and decreased incidence in summer months. A 2014 retrospective analysis reported that implementation of rotavirus vaccines has reduced diarrhea-related healthcare use in US children by as much as 94% in 2009–2010.[17, 18]
With the continued decline of rotavirus-associated gastroenteritis since the introduction of rotavirus vaccines, noroviruses (Norwalk-like viruses) have become the leading cause of medically attended acute gastroenteritis in children younger than 5 years in the United States, accounting for 14,000 hospitalizations, 281,000 emergency department visits, 627,000 outpatient visits, and more than $273 million in treatment costs each year.[19] Approximately half of the norovirus-related visits involved children aged 6-18 months according to a 2013 study from the US Centers for Disease Control and Prevention (CDC).[19, 20, 21] It has been estimated that globally norovirus resulted in a total of $4.2 billion in direct health system costs and $60.3 billion in societal costs per year.[14] Among this $60.3 billion, disease among children less than 5 years of age cost society $39.8 billion compared to $20.4 billion for all other age groups. Norovirus poses a considerable economic burden for both in high and low income countries and exceeds that of rotavirus. Rotavirus has been a target for vaccine because it kills more young children. Currently there is no approved vaccine against norovirus.[14]
Caliciviruses, astroviruses, and enteric adenoviruses make up the remainder of cases of viral gastroenteritis. Viral gastroenteritis typically presents with low-grade fever and vomiting followed by copious watery diarrhea (up to 10-20 bowel movements per day), with symptoms persisting for 3-8 days.[22] In high-resource settings, bacterial pathogens account for a small portion, perhaps 2-10%, of all cases of pediatric gastroenteritis. In the United States, the most important pathogens, in order of prevalence, are Campylobacter, Salmonella, Shigella, and enterohemorrhagic Escherichia coli (EHEC) species.[22] Relative to viral gastroenteritis, bacterial disease is more likely to be associated with high fevers, shaking chills, bloody bowel movements (dysentery), abdominal cramping, and fecal leukocytes.
In low-resource settings, a community-based cohort study enrolling patients from 8 sites in South America, Africa, and Asia found Norovirus, rotavirus, Campylobacter, astrovirus, and Cryptosporidium to be the most common causes of diarrhea overall in the first year of life, while Campylobacter, norovirus, rotavirus, astrovirus, and Shigella were the most common causes in the second year of life.[23] In this study, a causative agent was identified in less than one-third of cases, however. A recent case-control study conducted in 7 countries in Africa and South Asia specifically investigated causes of moderate-severe diarrhea in children under five. Using quantitative PCR analysis, they were able to identify causes for about 90% of cases, with the six most common being Shigella, rotavirus, adenovirus, ETEC, Cryptosporidium, and Campylobacter, though they found significant variation based on geography, seasonality, and severity of illness.[23] Of note, Shigella was by far the most common cause of bloody diarrhea in children, but also a common cause of watery diarrhea as well.
Clostridium difficile has emerged as an important cause of antibiotic-associated diarrhea in children. Any antibiotic can trigger infection with C difficile, though certain penicillins (e.g. co-amoxiclav) , cephalosporins, clindamycin and flouroquinolones are the most likely causes.[24] C. difficile testing in infants younger than 1 year of age is not recommended due to the high rates of colonization (37%). The rate of colonization decreases as age increases.[25]
Parasites remain yet another source of gastroenteritis in young children, with Giardia and Cryptosporidium the most common causes in the United States. Parasitic gastroenteritis generally present with watery stools but can be differentiated from viral gastroenteritis by a protracted course or history of travel to endemic areas.[26]
The vast majority of children presenting with acute gastroenteritis do not require serum or urine tests, as they are unlikely to be helpful in determining the degree of dehydration. In a meta-analysis of 6 studies, only serum bicarbonate (< 17) had statistically significant positive and negative likelihood ratios for detecting moderate dehydration.[27] Serum bicarbonate is also most closely associated (inversely) with the clinical dehydration scale (CDS) score out of all the tested urine biomarkers.[28]
Clinically significant electrolyte abnormalities are rare in children with moderate dehydration. However, any child being treated with intravenous fluids for severe dehydration should have baseline electrolytes, bicarbonate, and urea/creatinine drawn. Laboratory tests are also indicated in patients with moderate dehydration whose history and physical examination are inconsistent with straightforward gastroenteritis.
Fecal leukocytes and stool culture may be helpful in children presenting with bloody diarrhea or recent travel to a low-resource setting. Children older than 12 months of age with a recent history of antibiotic use should have stool tested for C difficile toxins. Those with a history of prolonged watery diarrhea (>14 d) or travel to an endemic area should have stool sent for ova and parasites.
Any child with evidence of systemic infection should have a complete workup, including complete blood count (CBC) and blood cultures. If indicated, urine cultures, chest radiography, and/or lumbar puncture should be performed.
Abdominal films are not indicated in the management of acute gastroenteritis. If the clinician suspects a diagnosis other than acute gastroenteritis based on history and physical examination findings, appropriate imaging modalities should be pursued.
A study looked to determine the predictive value of ultrasonography (US) for appendicitis in children when combined with clinical assessment based on the Pediatric Appendicitis Score (PAS). The study concluded that ultrasound findings in children with possible appendicitis should be integrated with clinical assessment, such as a clinical score, to determine next steps in management. Rates of false-negative US increase with increasing PAS, and false-positive US results occur more often with lower PAS. When discordance exists between US results and the clinical assessment, serial examinations or further imaging are warranted.[29] As US sensitivity is limited, non-visualization of the appendix and non-diagnostic US results can be followed by clinical reassessment and complementary imaging with MRI/CT.[30]
Corrected carotid flow time was found to be a poor predictor of severe dehydration (those with hypovolemia) in a prospective cohort study that enrolled a sample of 350 children age 0-60 months presented with acute diarrhea in Bangladesh.[31] This finding contrasts with previous studies that found this tool to be effective in predicting volume status and fluid responsiveness in adults.[31]
Ultrasound of the inferior vena cava to aorta ratio has been shown to be associated with overall volume status in children, a recent large study did not find it sensitive or specific enough to use as an independent tool for the diagnosis of dehydration in children with diarrhea.[32] A meta-analysis found that beside ultrasound may help in ruling out dehydration but should not be used to confirm the presence of dehydration. In addition, current evidence does not support the routine use of ultrasound or urinalysis to determine dehydration severity.[33]
Workup of acute gastroenteritis should begin by using elements of the history and physical examination to determine level of dehydration. Both the Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics (AAP) recommend using a simple dehydration scale to classify the total body water loss occurring with dehydration as minimal/none (< 3%), mild/moderate (3-9%), or severe (>10%) (see Table 1 below).[8] The World Health Organization (WHO) recommends a simpler system for use by both physicians and lay health workers, which classifies dehydration as none, some, or severe.
Some studies have found that combinations of clinical signs, symptoms, diagnostic tools and laboratory test may have better sensitivity and specificity for detecting dehydration in children than individual signs or symptoms.[33, 34]
The golden standard to detect the level of dehydration in children remains the percentage change between pre-illness weight and admission weight. However, pre-illness weight is rarely available in limited-resource settings. There are standardized scales that can assist in evaluating dehydration and their efficacy is discussed below. The four scales are the WHO algorithms, the Gorelick scale, the Clinical Dehydration Scale (CDS), and finally the DHAKA score.
A review of the first three clinical prediction models by Freedman et al found that the CDS and Gorelick scales consistently reported sensitivity of more than 80% in identifying dehydration in high-income countries, though acknowledges that at least one study by Jauregui, et al reported lower values.[33, 35] The authors conclude that the scales provide some improved diagnostic accuracy, but substantial gap remains in how well the scores predict the outcome of interest. Future research should focus on clarifying the efficacy of the existing dehydration assessment tools, especially the WHO algorithm because of its international usage, and develop new tools, especially those that can be used in low-resourced settings, with greater accuracy.
The Dehydration: Assessing Kids Accurately (DHAKA) scale is a newly developed tool. The DHAKA Dehydration Score comprises of 4 clinical signs: general appearance, skin pinch, tears, and respiration. The DHAKA Score has been internally and externally validated and concluded to be statistically more accurate and reliable than the WHO algorithm when used in children with acute diarrhoea in a low-income country.[36]
One potential obstacle to the accurate assessment of dehydration status is acute malnutrition. The WHO cites difficulty in using clinical signs alone to assess the dehydration status in severely malnourished children because there is a potential for the clinical signs to be distorted by malnutrition. However, one study found that, contrary to this recommendation, clinical signs of dehydration are as accurate in children with acute malnutrition as in children without acute malnutrition.[37] However, children with bilateral pitting edema (3.8% children) was excluded from the study. In addition, acute malnutrition did not have a significant effect on the accuracy of the DHAKA score, the WHO scale, or the CDS to predict any dehydration.
Table 1. Assessment of Dehydration*
View Table
See Table
Table 2. Assessment of Dehydration According to the World Health Organization*
View Table
See Table
Table 3:
Clinical Dehydration Scale
View Table
See Table
Adapted from Parkin PC, Macarthur C, Khambalia A, Goldman RD, Friedman JN. Clinical and laboratory assessment of dehydration severity in children with acute gastroenteritis. Clin Pediatr (Phila). 2010 Mar;49(3):235–9.
Total: ≥4 severe dehydration, 2-3 some dehydration, 0-1 no dehydration
Adapted from: External Validation of the DHAKA score and comparison to the current IMCI algorithm for the assessment of dehydration in children with diarrhoea. Lancet Global Health. 2016 Oct;4(10):e744-51.
Children with acute gastroenteritis rarely require intravenous access. In those presenting with circulatory collapse due to severe dehydration or sepsis, intravenous access should be obtained and followed by an immediate 20 mL/kg bolus of normal saline.
The American Academy of Pediatrics (2012), the European Society of Pediatric Gastroenterology (2014) and Nutrition (ESPGAN), the Center for Disease Control (CDC) (2003), and the World Health Organization (2004) all recommend oral rehydration solution (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.[5, 6, 7, 8]
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.[38] It has been reported that for every 25 children who are started on oral rehydration therapy, one would fail and require intravenous therapy (i.e. 4% failure rate).[39]
Initial care in the emergency department should focus on correction of dehydration. The type and amount of fluid given should reflect the degree of dehydration in the child.
A study reported sustained improvement in acute gastroenteritis care as a result of a clinical care pathway that emphasizes oral rehydration therapy and ondansetron for children with acute gastroenteritis. A downward shift in the percentage of patients receiving IV fluids was reported from 48% to 26% after initiation of the pathway and later with addition of ondansetron. The study also reported a decrease from 247 to 172 minutes in average emergency department length of stay for discharged patients with acute gastroenteritis.[40]
Minimal or no dehydration
No immediate treatment is required. If the child is breastfed, the mother should be encouraged to breastfeed more frequently than usual and for longer at each feed. If the child is not exclusively breastfed, then oral maintenance fluids (including clean water, soup, rice water, yogurt drink, or other culturally appropriate fluid) should be given at a rate of approximately 500 mL/day for children younger than 2 years, 1000 mL/day for children aged 2-10 years, and 2000 mL/day for children older than 10 years.
In addition, ongoing fluid losses should be replaced with 10 mL/kg body weight of additional ORS for each loose stool and 2 mL/kg body weight of additional ORS for each episode of emesis (both for breastfed and non-breastfed children).
A study of 647 children in Canada by Freedman et al found that patients with mild gastroenteritis and minimal dehydration experienced fewer treatment failures when offered half-strength apple juice followed by their preferred drinks compared with children given a standard electrolyte maintenance solution. As a result, fewer children administered apple juice required subsequent IV rehydration.[41]
Mild-to-moderate dehydration
Children should be given 50-100 mL/kg of ORS over a 2- to 4-hour period to replace their estimated fluid deficit, with additional ORS given to replace ongoing losses (10 mL/kg body weight for each stool and 2 mL/kg body weight for each episode of emesis). After the initial rehydration phase, patients may be transitioned to maintenance fluids as described above.
ORS should be given slowly by the caregiver or parent using a teaspoon, syringe, or medicine dropper at a rate of 5 mL every 1-2 minutes. If tolerated by the patient, the rate of ORS delivery can be increased slowly over time.
For patients who do not tolerate ORS by mouth, nasogastric (NG) feeding is a safe and effective alternative. Multiple clinical trials have found NG rehydration to be as efficacious as intravenous rehydration, but more cost-effective and with fewer adverse events and shorter hospital stay.[42, 43, 44] Therefore, ORS and NG are recommended as first-line treatment options before IV administration for mild-to-moderate dehydration.
Patients should be reassessed frequently by the clinician to ensure adequacy of oral intake and resolution of the various signs and symptoms of dehydration.
Severe dehydration
Severe dehydration constitutes a medical emergency requiring immediate resuscitation with intravenous fluids. Intravenous access should be obtained, and patients should be administered a bolus of 20-30 mL/kg lactated Ringer's (LR) or normal saline (NS). If pulse, perfusion, and/or mental status do not improve, a second bolus should be administered. After this, the patient should be given an infusion of 70 mL/kg LR or NS over 5 hours (children < 12 months) or 2.5 hours (older children). If no peripheral veins are available, an intraosseous line should be placed. Serum electrolytes, bicarbonate, urea/creatinine, and glucose levels should be sent.
Once resuscitation is complete and mental status returns to normal, rehydration should continue with ORS as described above, as it has been shown to decrease the rate of hyponatremia and hypernatremia when compared with intravenous rehydration.
Type of ORS
A large CochraneDatabase of Systematic Reviews meta-analysis confirmed several earlier studies showing that reduced osmolarity ORS (osmolarity: 245 mmol/L; sodium: 75) is associated with fewer treatment failures, lower stool output, and less frequent vomiting compared with standard osmolarity ORS for patients with noncholera gastroenteritis.[45] However, patients with cholera appear to have higher rates of hyponatremia with reduced osmolarity ORS compared with standard osmolarity ORS, without any of the added benefits seen in patients with noncholera gastroenteritis.[46] Nonetheless, the WHO 2005 guideline assessed that the reduced osmolarity solution appeared to be as safe and at least as effective as the standard solution for use in children with cholera.[8]
Multiple preparations of reduced osmolarity ORS are available in the United States, including Pedialyte, Infalyte, and Naturalyte. Available formulations in Europe include Dioralyte and Diocalm Junior. In developing countries, clinicians can use WHO reduced osmolarity ORS sachets or a homemade solution of 3 g (1 teaspoon) salt and 18 g (6 teaspoon) sugar added to 1 liter of clean water.
A systematic Cochrane review by Gregorio et al found that polymer-based ORS, made from complex carbohydrates such as rice, wheat, or maize, shows advantages compared to glucose-based ORS with osmolarity over 310 mmol/L.[47] Polymer-based ORS may reduce stool output in the first 24 hours and the duration of diarrhoea, albeit supported by low quality of evidence. Comparisons also favoured polymer-based ORS over ORS with osmolarity less than 270 mmol/L but this analysis is underpowered according to the authors.
The possible mechanism of polymer-based ORS is that carbohydrates are slowly digested in the small intestine, releasing glucose to facilitate sodium uptake without adding a significant osmotic load to bowel contents. Although currently not widely available in the United States, polymer-based ORS may become the preferred solution for oral rehydration of children with diarrhea in the future.
Feeding and nutrition
In general, children with gastroenteritis should be returned to a normal diet as rapidly as possible. Early feeding reduces illness duration and improves nutritional outcome.
Breastfed infants should continue breastfeeding throughout the rehydration and maintenance phases of acute gastroenteritis. Formula fed infants should restart feeding at full strength as soon as the rehydration phase is complete (ideally in 2-4 h). Weaned children should restart their normal fluids and solids as soon as the rehydration phase is complete. Fatty foods, foods high in simple sugars, commercial carbonated beverages, commercial fruit juices and sweetened tea should be avoided.
There is a lack of research into the benefits of lactose-free formulas over lactose-containing formulas or the benefits of highly specific diets, such as the BRAT (bananas, rice, applesauce, and toast). Eating solely BRAT may provide suboptimal nutrition for patients.
The goals of pharmacotherapy are to reduce morbidity, to prevent complications, and for 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. Two large systematic reviews have found probiotics (especially Lactobacillus GG) to be effective in reducing the duration of diarrhea in children presenting with acute gastroenteritis, though most of the included studies focused on patients in the inpatient rather than outpatient setting and included mostly patients in low and middle-income countries.[48, 49] A more recent randomized trial conducted in the US and Canada found that among children with acute gastroenteritis, those who received a 5-day course of Lactobacillus GG did not have shorter duration of diarrhea or shorter duration of vomit than those who received placebo.[50] At the same time, another recent meta-analysis found probiotics may be especially effective for the prevention of C difficile –associated diarrhea in patients receiving antibiotics.[51] As probiotic preparations vary widely, it is difficult to estimate the effectiveness of any single preparation.
The World Health Organization (WHO) recommends zinc supplementation (10-20 mg/day for 10-14 days) for all children younger than 5 years with acute gastroenteritis. According to one systematic review, little data exist to support this recommendation for children in developed countries, children who are well-nourished (i.e. low risk of zinc deficiency) and children younger than 6 months of age.[52] In another systematic review, zinc shows effectiveness with moderate quality of evidence for developing countries, where zinc deficiency and malnutrition is prevalent.[53] Zinc is also inexpensive and has shown cost-effectiveness in developing countries, but is associated with episodes of vomiting, which is a cause for future research.[53]
Clinical Context:
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. The AAP expressed no preference for either Rotateq or Rotarix. The first dose of rotavirus vaccine should be administered before the child is 15 weeks of age. The minimum interval between doses of rotavirus vaccine is 4 weeks. All doses should be administered by 8 months. While ideally the same vaccine should be used for each dose, in a clinical setting where it is not possible to obtain a product, the AAP says that immunization should not be deferred and that a mixed vaccine schedule can be utilized. A 2016 randomized study supports this recommendation, concluding that mixed schedules for rotavirus vaccines are safe and effective compared to single vaccine schedules.66
Vaccine efficacy is generally lower in countries with higher level of child mortality (i.e. low- and middle-income countries). However, both vaccines are effective against rotavirus gastroenteritis across a range of mortality settings and different nations. In middle- and low-income countries, it is particularly important that patients receive the full schedule of vaccination.
In February 2006, the US Food and Drug Administration (FDA) approved the RotaTeq vaccine for prevention of rotavirus gastroenteritis. The American Academy of Pediatrics (AAP) has endorsed the vaccine and recommended that the vaccine be administered as a 3-dose series at 2, 4, and 6 months of age.[54] RotaTeq is a pentavalent vaccine that contains 5 live reassortant rotaviruses and protects against G1, G2, G3, and G4 serotypes, the 4 most common rotavirus group A serotypes. It also contains attachment protein P1A (genotype P[8]).
In April 2008, the FDA approved Rotarix, another oral vaccine, for prevention of rotavirus gastroenteritis. The current AAP recommendation is to administer 2 separate doses of Rotarix to infants at 2 and 4 months of age.[54] Rotarix protects against rotavirus gastroenteritis caused by G1, G3, G4, and G9 strains.
Clinical Context:
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.
Clinical Context:
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).
Clinical Context:
Broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. Almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations.
Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. May block dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Treatment of choice for cholera. Not recommended for children younger than 8 years.
Because most 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 prolong the carrier state (Salmonella) or may increase the risk of hemolytic uremic syndrome (enterohemorrhagic E coli).[55, 56]
In patients with positive stool assays or high clinical suspicion for C difficile, the offending antibiotic should be stopped immediately. For non-severe episodes, either metronidazole or vancomycin is recommended with insufficient evidence to recommend one over the other. For a first-occurence, severe episode, vancomycin is recommended and the addition of metronidazole IV is optional. For a recurring, severe episode, rifaximin should follow vancomycin.[57]
Metronidazole and tinidazole are first-line drugs and have been found to have similar efficacies, with cure rate up to 90% of patients. Tinidazole has a similar regiment and fewer side effects. Albendazole and nitazoxanide are second-line drugs and might be difficult to obtain or not licensed in some countries. Paromomycin is the only second-line drug that can be used for pregnant women and quinacrine is usually reserved for difficult cases because it has numerous side effects.[58]
The WHO in 2017 recommended single-dose azithromycin (20 mg/kg) as a first-line therapy for treating pediatric cholera infection.[59] Antibiotic therapy should be extended to include children presenting with moderate to severe dehydration, especially in resource-constrained settings. Ciprofloxacin and doxycycline have demonstrated increasing resistance and should be used only in settings with documented pathogen susceptibility. Ciprofloxacin is not recommended for children and doxycycline is not recommended for children younger than 8. Erythromycin exhibits more adverse effects than azithromycin.
A prospective, multicenter, double-blind randomized controlled trial found that in children who continues to vomit after the first oral rehydration therapy attempt (ORT), a single dose of ondansetron significantly improved the success of ORT and reduced the need for IV therapy and the number of patients with episodes of vomiting during emergency department stay, compared to a placebo and the drug domperidone.[60] Another randomized control trial found that rotavirus-infected children treated with ondansetron had fewer diarrhea episodes and fewer days with clinical symptoms.[61] These trials were conducted in developed countries (Italy and Sweden respectively).
Ondansetron provides the strongest evidence for effectiveness in two systematic reviews. The evidence is less strong or uniform about other antiemetics such as metoclopramide and dimenhydride. There is nonetheless some evidence for metoclopramide and dimenhydride’s effectiveness, but they are believed to have some serious side effects.[62, 63, 64] The majority of studies included in the reviews focus on children in developed countries. More research is needed to address whether the purported effectiveness of ondansetron is also found in low-resourced settings. Another study conducted in Pakistan by Freedman et al reported that an oral, single dose of ondansetron did not reduce the use of intravenous rehydration and did not improve clinical outcomes in children without dehydration.[65]
A review of 7 randomized, controlled trials in children found that oral ondansetron reduced vomiting and the need for intravenous (IV) rehydration and hospital admission, IV ondansetron and metoclopramide reduced the number of episodes of vomiting and hospital admission, and dimenhydrinate suppository reduced the duration of vomiting.[55, 56]
A previous large, prospective, randomized, double-blind trial compared a single dose of an orally disintegrating ondansetron tablet with placebo in children presenting to an emergency department with acute gastroenteritis.[57] This study also found that children treated with ondansetron were less likely to vomit and that they had greater oral intake, were less likely to require IV rehydration, and had a reduced length of stay in the emergency department compared with children treated with placebo.
Several smaller studies have also demonstrated ondansetron to be effective in children.[55, 58]
Parents should be instructed to continue providing maintenance ORS fluids at home as needed. Breastfeeding and formula feeding should be continued for infants, and children should be encouraged to return to a regular diet as rapidly as possible.
Parents should be instructed to look for the various signs of dehydration outlined above, such as change in mental status, decreased urine output, sunken eyes, absence of tears, dry mucous membranes, and slow return of abdominal skin pinch.
Parents should seek medical attention if dehydration returns, oral intake is inadequate, or if their child develops worsening abdominal pain, fever >101°F, or prolonged diarrhea lasting longer than 14 days.
Inpatient admission should be considered for all children with acute gastroenteritis in the following situations:
Signs of severe dehydration are present.
Caregivers are unable to manage oral rehydration or provide adequate care at home.
Substantial difficulties exist in administering ORS, such as intractable vomiting or inadequate ORS intake.
Failure of treatment occurs, such as worsening diarrhea or dehydration, despite adequate ORS intake.
Factors are present necessitating closer observation, such as young age, decreased mental status, or uncertainty of diagnosis.
Children with mild-moderate dehydration, age < 6 months, or high frequency of stools/vomits should be monitored in the emergency department for a minimum of 4-6 hours before discharge.
The US Advisory Committee on Immunization Practices and the American Academy of Pediatrics recommend routine vaccination of US infants with rotavirus vaccine to protect against rotavirus gastroenteritis.[18]
Adam C Levine, MD, MPH, Associate Professor of Emergency Medicine, The Warren Alpert Medical School of Brown University
Disclosure: Nothing to disclose.
Coauthor(s)
Huy Nguyen, Brown University
Disclosure: Nothing to disclose.
Karen A Santucci, MD, MD,
Disclosure: Nothing to disclose.
Specialty Editors
Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Wayne Wolfram, MD, MPH, Professor, Department of Emergency Medicine, Mercy St Vincent Medical Center; Chairman, Pediatric Institutional Review Board, Mercy St Vincent Medical Center, Toledo, Ohio
Disclosure: Nothing to disclose.
Chief Editor
Kirsten A Bechtel, MD, Associate Professor of Pediatrics, Section of Pediatric Emergency Medicine, Yale University School of Medicine; Co-Director, Injury Free Coalition for Kids, Yale-New Haven Children's Hospital
Disclosure: Nothing to disclose.
Additional Contributors
James Li, MD, Former Assistant Professor, Division of Emergency Medicine, Harvard Medical School; Board of Directors, Remote Medicine
Disclosure: Nothing to disclose.
Acknowledgements
The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, David W Marby, MD †, to the development and writing of this article.
Laidman J. Rotavirus Vaccine Greatly Reduced Healthcare Use. Medscape Medical News. Available at http://www.medscape.com/viewarticle/826391. June 09, 2014; Accessed: February 28, 2019.
Waknine Y. Norovirus Is Now the Main Cause of Acute GI Problems in Kids. Medscape Medical News. Available at http://www.medscape.com/viewarticle/781459. Mar 26, 2013; Accessed: Apr 3, 2013.
Norovirus is now the leading cause of severe gastroenteritis in US children. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/media/releases/2013/p0321_norovirus_children.html. Mar 21, 2013; Accessed: Apr 3, 2013.
Kazimbaya KM, Bosomprah S, Simuyandi M, et al. Efficacy and Effectiveness of Rotavirus Vaccine on Incidence of Diarrhoea among Children: A Meta-analysis./ Pediatric Infectious Diseases:. Open Access. 2018. 3 (1): 4:
