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842 SECTION 12: Pediatrics TABLE 130-8 Age-Specific ECG Intervals44 Age PR (seconds) QRS (seconds) QTc (seconds) Birth–4 wk 0.08–0.12 0.05–0.09 0.38–0.46 1–3 mo 0.08–0.13 0.05–0.08 0.38–0.46 3–6 mo 0.08–0.14 0.05–0.09 0.39–0.45 6–12 mo 0.08–0.14 0.05–0.09 0.38–0.45 1–3 y 0.08–0.15 0.05–0.09 0.38–0.45 3–5 y 0.1–0.15 0.06–0.09 0.38–0.45 5–8 y 0.09–0.16 0.06–0.1 0.37–0.45 8–12 y 0.1–0.17 0.07–0.1 0.37–0.45 12–16 y 0.1–0.18 0.7–0.11 0.36–0.46 TABLE 130-9 Voltage Criteria for Left Ventricular Hypertrophy (LVH) and Right Ventricular Hypertrophy (RVH) by Age42,45 Age 0–7 d 7 d–1 y 1–3 y 3–5 y >5 y LVH RV6 >12 mm >23 mm >21–23 mm >24–25 mm >25–27 mm SV1 >23 mm >15–18 mm >21 mm >22 mm >26 mm SV1 + RV6 >28 mm >35 mm >38 mm >42 mm >47 mm RVH 1 >26 mm >20–22 mm >18 mm >14–18 mm >13 mm SV6 >10 mm >7–10 mm >7 mm >6 mm >4 mm RV1 + SV6 >37 mm >43 mm >30 mm >24 mm >17 mm  PR, QRS, AND QT INTERVALS The PR interval varies with age, gradually lengthening from 0.08 to 0.12 seconds in neonates to 0.11 to 0.18 seconds in adolescents. 36 The QRS interval also lengthens over time from 0.05 to 0.09 seconds in the neonate to 0.07 to 0.11 seconds in the adolescent. 44 The QT inter val (measured from the onset of the QRS complex to the end of the T wave) is subject to variations in heart rate, and a correction for heart rate is calculated using Bazett’s formula: QT c = QT/the square root of the RR interval. The QTc should be <0.49 seconds in the first 6 months of life and <0.44 seconds thereafter, although different definitions for prolonged QTc have been suggested.42 Age-specific normal intervals are listed in Table 130-8.  T WAVES Pediatric T-wave changes are typically nonspecific. Flat or inverted T waves are usually normal in the newborn. T-wave inversion in the right pre cordial leads is common in the first years of life and may persist into adolescence or revert in early childhood to the typical upright pattern seen in adults. 42 T-wave changes are common in infants and children and rarely reflect ischemia.  CHAMBER SIZE Evaluating the ECG for signs of chamber size is important when con sidering congenital or acquired heart disease in the pediatric patient. P-wave amplitude is relatively age independent and best measured in lead II. P waves >0.25 mV should be considered abnormal and may indicate right atrial enlargement. 44 Left atrial enlargement is suggested by prolonged P-wave duration, which should not be >0.08 seconds in infants or >0.12 seconds in adolescents. 42 Voltage criteria for left ventricular hypertrophy and right ventricular hypertrophy depend on age and are listed in Table 130-9. 42,45 Left ventricular hypertrophy is also suggested by a q-wave amplitude >4 mm in V5 or V6 or inverted T wave in V 6, whereas right ventricular hypertrophy is suggested by an RSR ′ pattern in V1 with an R′ >15 mm in infants or >10 mm in children after the first year of life, or with a q wave in lead V 1.33,42,43 REFERENCES The complete reference list is available online at www.TintinalliEM.com. Vomiting, Diarrhea, and Dehydration in Infants and Children Stephen B. Freedman Jennifer Thull-Freedman INTRODUCTION Acute viral gastroenteritis is the most common cause of vomiting and diarrhea in children and continues to account for over 500,000 deaths globally each year in children <5 years old.

w.TintinalliEM.com. Vomiting, Diarrhea, and Dehydration in Infants and Children Stephen B. Freedman Jennifer Thull-Freedman INTRODUCTION Acute viral gastroenteritis is the most common cause of vomiting and diarrhea in children and continues to account for over 500,000 deaths globally each year in children <5 years old. 1 Transmission of GI infec tions can be reduced by attention to good hand washing, which can reduce the incidence of diarrheal disease by approximately 30% in both high- and low-income countries. 2 The provision of alcohol-based hand sanitizer and educational materials can reduce GI illnesses in child care centers, 3 and a multifactorial intervention including hand sanitizer and surface disinfection similarly reduces illness due to enteric pathogens in elementary school students. Rotavirus previously accounted for the majority of severe cases and contributed significantly to hospitalizations in developed countries. However, the introduction of two live oral rotavirus vaccines, marketed as RotaTeq ® and Rotarix ® , for use in the United States and numerous other countries has resulted in an approximately 80% reduction in rotavirus-related hospitalizations and ED visits for rotavirus among immunized children. 5,6 Although a prospective postlicensure study of more than 200,000 doses identified an increase in the rate of intus susception after vaccination (attributable risk ~5.3 per 100,000 infants vaccinated), the increased risk must be weighed against the benefits of preventing rotavirus-associated illness. 7 The reduction in rotavirus’s burden of disease along with the improved ability to identify norovirus has led to a realization that norovirus is now the pathogen responsible for the greatest burden of medically attended cases of gastroenteritis. Although the clinical diagnosis of gastroenteritis requires the pres ence of diarrhea, many infants present with isolated vomiting. This chapter focuses on one of the most frequent and important causes of vomiting and diarrhea in children, gastroenteritis, and will also review other important causes of these symptoms. VOMITING Vomiting is the forceful act of expelling gastric contents through the mouth. It is controlled by the vomiting center in the reticular formation of the medulla and the chemoreceptor trigger zone underlying the floor of the fourth ventricle. Trigger areas that excite the CNS vomiting centers are found in the pharynx, cardiac vessels, peritoneum, bile ducts, and stomach. Vomiting results when the stomach relaxes, the gastric pylorus constricts, and the contractions of surrounding muscles cause expulsion of the gastric contents. Acute vomiting is usually caused by a self-limited viral illness. Nonetheless, serious diagnoses that need to be considered include infections, metabolic abnormalities, neurologic processes, acute surgical/GI diseases, or other major organ system dysfunction. The differential diagnosis of vomiting is age specific (Table 131-1). Bilious or bloody vomitus, hematochezia, or significant abdominal pain should trigger concerns of a disease process other than simple viral gastroenteritis or a potential complication of viral gastroenteritis (Tables 131-2 and 131-3). CHAPTER Tintinalli_Sec12_p0669-0996.indd 842 8/2/19 7:53 PM

e specific (Table 131-1). Bilious or bloody vomitus, hematochezia, or significant abdominal pain should trigger concerns of a disease process other than simple viral gastroenteritis or a potential complication of viral gastroenteritis (Tables 131-2 and 131-3). CHAPTER Tintinalli_Sec12_p0669-0996.indd 842 8/2/19 7:53 PM CHAPTER 131: Vomiting, Diarrhea, and Dehydration in Infants and Children 843 Bilious vomiting suggests an obstructive lesion distal to the ampulla of Vater and portends a surgical emergency. From one third to half of newborns with bilious vomiting have a surgical lesion, often malrota tion with volvulus or Hirschsprung’s disease.9,10 For further discussion, see Chapter 133, “ Acute Abdominal Pain in Infants and Children. ” For discussion of hematemesis, see Chapter 134, “Gastrointestinal Bleeding in Infants and Children. ” Diagnostically, it is important to consider children with isolated vomiting separately from those who present with vomiting and diarrhea. The differential diagnosis of vomiting is vast and age specific ( Table 131-1). Gastroesophageal reflux, intussusception, pyloric stenosis, and malrotation are discussed briefly below and more fully in Chapter 133, “ Acute Abdominal Pain in Infants and Children. ” GASTROESOPHAGEAL REFLUX (GERD) Gastroesophageal reflux is the spontaneous regurgitation of gastric contents into the esophagus. Reflux is physiologic in young infants and usually resolves by the end of the first year of life. It is considered pathologic only in the small subset that experiences complications.

ildren. ” GASTROESOPHAGEAL REFLUX (GERD) Gastroesophageal reflux is the spontaneous regurgitation of gastric contents into the esophagus. Reflux is physiologic in young infants and usually resolves by the end of the first year of life. It is considered pathologic only in the small subset that experiences complications. The typical infant with uncomplicated gastroesophageal reflux effortlessly TABLE 131-1 Causes of Vomiting, by Age Newborn Obstructive intestinal anomalies Esophageal stenosis/atresia, pyloric stenosis, intestinal stenosis/ atresia, malrotation ± volvulus, incarcerated hernia, meconium ileus/plug, Hirschsprung’s disease, imperforate anus, enteric duplications Neurologic Intracranial bleed/mass, hydrocephalus, cerebral edema, kernicterus Renal Urinary tract infection, obstructive uropathy, renal insufficiency Infectious Viral illness, gastroenteritis, meningitis, sepsis Metabolic/ endocrine Inborn errors of metabolism (urea cycle, amino/organic acid, carbohydrate), congenital adrenal hyperplasia Miscellaneous Ileus, gastroesophageal reflux, necrotizing enterocolitis, GI perforation Infant (<12 mo) Obstructive intestinal anomalies Pyloric stenosis, malrotation ± volvulus, incarcerated hernia, Hirschsprung’s disease, enteric duplications, intussusception, foreign body, bezoars, Meckel’s diverticulum Neurologic Intracranial bleed/mass, hydrocephalus, cerebral edema Renal Urinary tract infection, obstructive uropathy, renal insufficiency Infectious Viral illness, gastroenteritis, meningitis, sepsis, otitis media, pneumonia, pertussis, hepatitis Metabolic/ endocrine Inborn errors of metabolism, adrenal insufficiency, renal tubular acidosis Miscellaneous Ileus, gastroesophageal reflux, posttussive, peritonitis, drug overdose, food allergy Child (>12 mo) Obstructive intestinal anomalies Malrotation ± volvulus, incarcerated hernia, Hirschsprung’s disease, intussusception, foreign body, bezoars, Meckel’s diverticulum, acquired esophageal stricture, peptic ulcer disease, adhesions, superior mesenteric artery syndrome Neurologic Intracranial bleed/mass, cerebral edema, postconcussive, migraine Renal Urinary tract infection, obstructive uropathy, renal insufficiency Infectious Viral illness, gastroenteritis, meningitis, sepsis, otitis media, pneumonia, hepatitis, streptococcal pharyngitis Metabolic/ endocrine Inborn errors of metabolism, adrenal insufficiency, renal tubular acidosis, diabetes mellitus, Reye’s syndrome, porphyria Miscellaneous Ileus, gastroesophageal reflux, posttussive, peritonitis, drug overdose, food allergy, appendicitis, pancreatitis, gastritis, Crohn’s disease, pregnancy, psychogenic, cyclic vomiting syndrome TABLE 131-2 Causes of Vomiting With Significant Morbidity, by Age Newborn Period (birth–2 wk ) Obstructive intestinal anomaly Esophageal or intestinal stenosis/atresia, bowel malrotation ± midgut volvulus, meconium ileus/plug, Hirschsprung’s disease, imperforate anus, enteric duplications Other GI disease processes Necrotizing enterocolitis, perforation with secondary peritonitis Neurologic Mass lesion, hydrocephalus, cerebral edema, kernicterus Renal Obstructive anomaly, uremia Infectious Sepsis, meningitis Metabolic Inborn errors of metabolism, congenital adrenal hyperplasia Infant (2 wk–12 mo) Acquired esophageal disorders Foreign body, retropharyngeal abscess GI obstruction Bezoar, foreign body, pyloric stenosis, malrotation ± volvulus, enteric duplications, complications of Meckel’s diverticulum, intussusception, incarcerated hernia, Hirschsprung’s disease Other GI disease processes Gastroenteritis with dehydration, peritonitis Neurologic Mass lesion, hydrocephalus Renal Obstruction, uremia Infectious Sepsis, meningitis, pertussis Metabolic Inborn errors of metabolism Toxic ingestions — Child (>12 mo) GI obstruction Be

ception, incarcerated hernia, Hirschsprung’s disease Other GI disease processes Gastroenteritis with dehydration, peritonitis Neurologic Mass lesion, hydrocephalus Renal Obstruction, uremia Infectious Sepsis, meningitis, pertussis Metabolic Inborn errors of metabolism Toxic ingestions — Child (>12 mo) GI obstruction Be zoar, foreign body, posttraumatic intramural hematoma, malrotation ± volvulus, complications of Meckel’s diverticulum, intussusception, incarcerated hernia, Hirschsprung’s disease Other GI disease processes Appendicitis, peptic ulcer disease, pancreatitis, peritonitis Neurologic Mass lesions Renal Uremia Infectious Sepsis, meningitis Metabolic Diabetic ketoacidosis, adrenal insufficiency, inborn errors of metabolism Toxic ingestion — TABLE 131-3 Causes of Diarrhea With Significant Morbidity •   Infection:  Salmonella gastroenteritis with bacteremia, Shigella, Clostridium difficile (pseudomembranous colitis) •   Anatomic abnormalities •   Intussusception •   Hirschsprung’s disease with toxic megacolon •   Partial obstruction •   Appendicitis •   Inflammatory bowel disease with toxic megacolon •   Verotoxigenic Escherichia coli infection with the secondary development of hemolytic-uremic syndrome brings up small amounts of milk after feeding but continues to grow well. Symptoms may begin as early as the first week of life and often resolve around the time of solid food introduction and the assumption of the sitting position. In infants with significant vomiting, pathologic conditions should be considered. Complications that can occur include esophagitis, failure to thrive/weight loss , respiratory disease, refrac tory asthma, recurrent pneumonia, apnea, and acute life-threatening Tintinalli_Sec12_p0669-0996.indd 843 8/2/19 7:53 PM

osition. In infants with significant vomiting, pathologic conditions should be considered. Complications that can occur include esophagitis, failure to thrive/weight loss , respiratory disease, refrac tory asthma, recurrent pneumonia, apnea, and acute life-threatening Tintinalli_Sec12_p0669-0996.indd 843 8/2/19 7:53 PM 844 SECTION 12: Pediatrics events. In most infants, the diagnosis can be made based on clinical findings. The gold standard diagnostic test is continuous esophageal pH monitoring to detect the presence of gastric acid in the distal esophagus. Semi-supine positioning (e.g., infant carrier or car seat) may exacerbate gastroesophageal reflux and should be avoided, especially after feeding. Although severe cases may require a histamine-2 receptor antagonist or a proton pump inhibitor, the overuse of medications in the “happy spitter” should be avoided.  INTUSSUSCEPTION Intussusception occurs when one segment of bowel invaginates into a more distal segment. It is the leading cause of acute intestinal obstruc tion in infants and occurs most commonly between 3 and 12 months of age. The most common location is ileocolic, and the lead point usually is a hypertrophied Peyer patch. However, in children >2 years of age, a specific pathologic lead point should be considered. The pri mary manifestation is colicky abdominal pain followed by the onset of vomiting. The “classic” triad of colicky abdominal pain, vomiting, and bloody stools is present in only 20% of cases. For further discussion of intussusception, see Chapter 133, “ Acute Abdomnal Pain in Infants and Children. ”  PYLORIC STENOSIS Pyloric stenosis results from pyloric muscle hypertrophy that obstructs gastric outflow. The incidence is 1 in 250 live births, and >80% of cases occur in males 12; other risk factors include white race, first born birth order, and a positive family history. Over 90% of cases are diagnosed by 10 weeks of life, with a sharp increase in the incidence after the second week of life, peaking at the fifth week and then steadily declining until the 10th week. 12 Children typically present with nonbilious projectile vomiting associated with weight loss and dehydration. Initially, the vomiting is mild and often mistaken for regurgitation. However, vomiting progresses and becomes more severe over several days. ED treat ment includes the correction of fluid and electrolyte abnormalities. The pathognomonic electrolyte abnormalities are a hyponatremic, hypoka lemic, and hypochloremic metabolic alkalosis. At present, the diagnosis is usually confirmed by US.  MALROTATION Malrotation occurs when incomplete rotation of the gut in utero places the cecum in the right upper quadrant and fixes the dorsal mesentery on a narrow base instead of the broad fixation that usually extends from the ligament of Treitz to the ileocecal junction. These anomalies place the small bowel at risk for twisting on the narrow pedicle of mesentery, resulting in a volvulus that subsequently impairs blood flow to the bowel. Although malrotation can present at any age, roughly one third of patients present in the first month of life. 12 Symptoms may include bilious vomiting, pain, abdominal distention, and, ultimately, shock due to intestinal ischemia. Bilious emesis, particularly in a young infant, should immediately raise a concern for possible malrotation and volvulus. In some children, the volvulus can be intermittent, resulting in episodic vomiting and pain. Prompt diagnosis and surgical repair are needed to minimize the risk of bowel necrosis and death. DIARRHEA Diarrhea is loose or liquid stools and/or an increase in the frequency of evacuations with at least three stools in 24 hours. The child’s age and diet affect stool consistency and frequency.

dic vomiting and pain. Prompt diagnosis and surgical repair are needed to minimize the risk of bowel necrosis and death. DIARRHEA Diarrhea is loose or liquid stools and/or an increase in the frequency of evacuations with at least three stools in 24 hours. The child’s age and diet affect stool consistency and frequency. For example, in the first month of life, a change in stool consistency is more specific for diarrhea than absolute stool number. Breastfed infants typically have several poorly formed, yellow-green stools per day. Recognition of diarrhea in infants is important, because given their small size, they have limited fluid reserves and are at high risk for developing dehydration. Most children with diarrhea have an acute viral infection, but diar rhea may be a presenting symptom of many conditions ( Tables 131-4 and 131-5). Preexisting conditions may contribute to the clinical presentation or predispose the patient to an unusual cause of diarrhea, so it is important to inquire about previous GI surgery or chronic illnesses such as inflammatory bowel disease and immunodeficiency states. Bacterial and parasitic infections are more likely in institutionalized children and those returning from travel in low- and middle-income countries. Other causes of diarrhea include food allergies, antibiotic-associated diarrhea, and secondary lactase deficiency. Acute onset of bloody diarrhea suggests a bacterial cause and a need to perform stool cultures. If there is a known outbreak of Escherichia coli O157:H7 (STEC, or Shiga toxin-producing E. coli), or clinical features of hemolytic-uremic syndrome (HUS), obtain further testing to exclude renal failure, thrombocytopenia, and hemolytic anemia and provide early volume expansion. 13 An infant with intermittent, crampy abdominal pain, vomiting, and bloody stools raises concern for intussusception, pseudomembranous colitis, parasitic infection, or inflammatory bowel disease. DEHYDRATION Regardless of the cause of vomiting and diarrhea, the end result is fluid loss. Parental reports of dehydration, although highly sensitive, have a high false-positive rate. However, a history of normal fluid intake and normal urine output drastically reduces the likelihood of significant dehydration. 14 Thus, for the majority of children, the physical examina tion remains crucial and should begin by assessing the child’s overall appearance, level of activity, responsiveness, respiratory pattern, and vital signs. Although the American Academy of Pediatrics, Centers for Disease Control and Prevention, World Health Organization, and European Society for Paediatric Gastroenterology, Hepatology, and Nutrition have developed treatment guidelines based on the degree of dehydration, no single variable in isolation is sufficiently accurate to determine the severity of dehydration. 15 The percentage of body weight lost remains the gold standard measurement of dehydration, but it is infrequently available in the ED. Thus, while we recommend that physicians continue to rely on the presence of a combination of clinical findings as well as historical features to determine the degree of dehy dration (see Table 132-2), their ability to identify children both with and without dehydration is suboptimal. 16 Moreover, current evidence does not support the routine use of US or urinalysis to determine dehydra tion severity.

nation of clinical findings as well as historical features to determine the degree of dehy dration (see Table 132-2), their ability to identify children both with and without dehydration is suboptimal. 16 Moreover, current evidence does not support the routine use of US or urinalysis to determine dehydra tion severity. A validated dehydration score derived from several clinical studies, 17-19 which correlates with length of stay and need for IV rehydration, is described in Table 131-6.18 TABLE 131-4 Causes of Diarrhea Infection •   Viral: rotavirus, norovirus, enteric adenoviruses, sapoviruses, astroviruses •   Bacterial: Salmonella, Shigella, Yersinia, Campylobacter, Escherichia coli, Aeromonas hydrophila, Vibrio species, Clostridium difficile •   Parasitic: Giardia lamblia, Entamoeba histolytica, Cryptosporidium Dietary disturbances •   Overfeeding, food allergy, starvation stools Anatomic abnormalities •     Intussusception, Hirschsprung’s disease, partial obstruction, appendicitis, blind loop syndrome, intestinal lymphangiectasia, short bowel syndrome Inflammatory bowel disease Malabsorption or secretory diseases •   Cystic fibrosis, celiac disease, disaccharidase deficiency, acrodermatitis enteropathica, secretory neoplasms Systemic diseases •   Immunodeficiency, endocrinopathy (hyperthyroidism, hypoparathyroidism, congenital adrenal hyperplasia) Miscellaneous •   Antibiotic-associated diarrhea, secondary lactase deficiency, irritable colon syndrome, neonatal drug withdrawal, toxins, hemolytic-uremic syndrome Tintinalli_Sec12_p0669-0996.indd 844 8/2/19 7:53 PM

Immunodeficiency, endocrinopathy (hyperthyroidism, hypoparathyroidism, congenital adrenal hyperplasia) Miscellaneous •   Antibiotic-associated diarrhea, secondary lactase deficiency, irritable colon syndrome, neonatal drug withdrawal, toxins, hemolytic-uremic syndrome Tintinalli_Sec12_p0669-0996.indd 844 8/2/19 7:53 PM CHAPTER 131: Vomiting, Diarrhea, and Dehydration in Infants and Children 845 GASTROENTERITIS  EPIDEMIOLOGY Diarrheal diseases are the second leading cause of death worldwide in children outside of the neonatal period. Rotavirus is the most com mon pathogen in areas without a vaccination program, and in areas with widespread rotavirus vaccination, norovirus is the most common pathogen.  PATHOPHYSIOLOGY To cause diarrhea, an infectious agent must overcome numerous host defense factors, including gastric acidity, intestinal immunity, motility, mucus, and the resident microflora. The interaction between these factors and the infecting agent’s virulence mechanisms determines the subsequent clinical course (Table 131-5). No matter what the mechanism is, acute gastroenteritis is associated with fluid shifts and has the potential to cause dehydration, shock, and even death. The common final pathway results in fluid output exceeding the absorptive capacity of the GI tract. Fasting, which sometimes occurs with gastroenteritis, actually worsens the capacity of the bowel to absorb fluids. Continued feeding not only slows the progression of dehydration by increasing the volume of fluid available to the intravascular space, but the presence of nutrients in the bowel lumen also promotes mucosal recovery and improves fluid absorption.  CLINICAL FEATURES Diarrhea associated with acute viral gastroenteritis typically lasts <7 days and not longer than 14 days, and it may be accompanied by vomiting or fever. Clinical features associated with the most important causes of bacterial gastroenteritis are listed in Table 131-7. Isolated vomiting should not be diagnosed as acute gastroenteritis. The differential diagnosis for isolated vomiting in the absence of diarrhea is broad. Abdominal pain is often associated with gastroenteritis, but pain is typically poorly localized and crampy with no peritoneal signs on examination. If peritoneal signs are present, consider an alternative diagnosis, such as acute appendicitis. Although appendicitis typically manifests with abdominal pain followed by vomiting associated with constipa tion, it may also cause diarrhea, particularly once the appendix has perforated. This is presumed to occur because the inflammation irritates the colon, resulting in diarrhea. Stools tend to be frequent, mucus-containing, and small in volume. For further discussion, see Chapter 133, “ Acute Abdominal Pain in Infants and Children. ”  LABORATORY TESTING Obtain a CBC only if the child is ill appearing or has bloody diarrhea (mainly to identify bacterial enterocolitis or hemolytic-uremic syndrome). The WBC count and C-reactive protein are not reliable for distinguishing viral from bacterial gastroenteritis. 21-23 The C-reactive protein is only helpful for following activity of inflammatory bowel disease. Given that the reported prevalence of hypoglycemia may be as high as 9% in pediatric gastroenteritis,24 measuring serum glucose in infants and young children is essential. Obtain serum electrolytes only in specific circumstances.

e C-reactive protein is only helpful for following activity of inflammatory bowel disease. Given that the reported prevalence of hypoglycemia may be as high as 9% in pediatric gastroenteritis,24 measuring serum glucose in infants and young children is essential. Obtain serum electrolytes only in specific circumstances. 25,26 Table 131-8 lists the European Society for Paediatric Gastroenterology, TABLE 131-5 Mechanisms of Infectious Diarrheal Disease Pathogen Type Characteristic Examples Mechanism Pathologic Impact Clinical Impact Viral enteropathogens Rotaviruses Adenoviruses Invade small intestinal mucosa villous epithelium Loss of mature absorptive cells, producing a proliferative response, resulting in repopulation of intestinal epithelial lining with poorly differentiated cells. Salt and water absorption is decreased Carbohydrate malabsorption and osmotic diarrhea Bacterial enteropathogens Invasive Shigella Salmonella Yersinia enterocolitica Campylobacter jejuni Vibrio parahaemolyticus Adhere to mucosal cells followed by invasion and multiplication, primarily in large intestine Intramucosal multiplication elicits an acute mucosal inflammatory reaction, resulting in ulceration and synthesis of a variety of secretagogues. Salt and water absorption is decreased (secretory diarrhea) Cytotoxic Shigella Enteropathogenic Escherichia coli Enterohemorrhagic E. coli Clostridium difficile Elaboration of cytotoxins Cause cell damage and death by inhibiting protein synthesis or by inducing the secretion of one or more inflammatory mediator substances. Decreased intestinal absorptive surface Toxigenic Shigella Enterotoxigenic E. coli Y. enterocolitica Aeromonas Vibrio cholerae Colonize small intestine and secrete enterotoxins Enterotoxin binds to specific mucosal receptors, increasing the concentration of an intracellular mediator (adenosine 3′:5′-cyclic phosphate or cyclic guanosine monophosphate). Alter intestinal salt and water transport without affecting mucosal morphology Adherent Enteropathogenic E. coli Enterohemorrhagic E. coli Colonization and adherence to intestinal surface of small and large intestine Binding to epithelial cells indents the surface and causes glycocalyx dissolution and microvilli flattening. Decreased intestinal absorptive surface TABLE 131-6 Clinical Dehydration Score Score General Appearance Eyes Oral Mucosa (Tongue) Tears 0 Normal Normal Moist Normal 1 Thirsty, restless, lethargic but irritable Mildly sunken Sticky Decreased 2 Drowsy/nonresponsive, limp, cold, diaphoretic Very sunken Dry None Score >0 = some dehydration; score >5 = moderate-severe dehydration. Tintinalli_Sec12_p0669-0996.indd 845 8/2/19 7:53 PM

ral Mucosa (Tongue) Tears 0 Normal Normal Moist Normal 1 Thirsty, restless, lethargic but irritable Mildly sunken Sticky Decreased 2 Drowsy/nonresponsive, limp, cold, diaphoretic Very sunken Dry None Score >0 = some dehydration; score >5 = moderate-severe dehydration. Tintinalli_Sec12_p0669-0996.indd 845 8/2/19 7:53 PM 846 SECTION 12: Pediatrics TABLE 131-7 Clinical Features and Treatment of Bacterial Gastroenteritis 24 Organism Typical Clinical Features Risk Factors Complications Antimicrobial Therapy* Shigella Ranges from watery stools without constitutional symptoms to fever, abdominal pain, tenesmus, mucoid stools, hematochezia; Shigella dysenteriae serotype 1 causes more severe symptoms Contact with infected host or fomite, poor sanitation, crowded living conditions, day care Pseudomembranous colitis, toxic megacolon, intestinal perforation, bacteremia, Reiter’s syndrome, hemolytic-uremic syndrome, encephalopathy, seizures, hemolysis Typically self-limited Treat if: immunocompromised, severe disease, dysentery or systemic symptoms If susceptibility unknown: azithromycin, ceftriaxone, ciprofloxacin; if susceptible, ampicillin or trimethoprim-sulfamethoxazole Salmonella Nontyphoidal: may be asymptomatic or cause watery diarrhea, mild fever, abdominal cramps Enterica serotypes: “enteric fever” may include high fever, constitutional symptoms, headache, abdominal pain, dactylitis, hepatosplenomegaly, rose spots, altered mental status Direct contact with animals: poultry, livestock, reptiles, pets; consuming food contaminated by human carrier: beef, poultry, eggs, dairy, water Meningitis, brain abscess, osteomyelitis, bacteremia, dehydration, endocarditis, enteric (typhoid or paratyphoid) fever Typically self-limited Treat if: <3 mo of age, hemoglobinopathy, immunodeficiency, chronic GI tract disease, malignancy, severe colitis, bacteremia, sepsis Options: ampicillin, amoxicillin, trimethoprim-sulfamethoxazole; if resistant, azithromycin, fluoroquinolone Invasive disease: cefotaxime, ceftriaxone Campylobacter Diarrhea, hematochezia, abdominal pain, fever, malaise Contamination from poultry feces or undercooked poultry, untreated water, unpasteurized milk, pets (dogs, cats, hamsters, birds); person-to-person transmission possible Acute: dehydration, bacteremia, focal infections, febrile seizures Convalescence: reactive arthritis, Reiter’s syndrome, erythema nodosum, acute idiopathic polyneuritis, Miller Fisher syndrome, myocarditis, pericarditis Often self-limited; 20% have relapse or prolonged symptoms Treat if: moderate-severe symptoms, relapse, immunocompromised, day care and institutions Options: erythromycin, azithromycin, ciprofloxacin Escherichia coli–Shiga toxin producing Initially nonbloody diarrhea, often becoming bloody; severe abdominal pain Food or water contaminated with human or cattle feces, undercooked beef, unpasteurized milk Hemorrhagic colitis, hemolytic-uremic syndrome None indicated; increased incidence of hemolytic-uremic syndrome with treatment E. coli– enteropathogenic Severe watery diarrhea, usually children <2 years in resource-limited countries Food or water contaminated with feces Dehydration Treat if severe Options: trimethoprim-sulfamethoxazole, azithromycin, ciprofloxacin E. coli– enterotoxigenic Moderate watery diarrhea, abdominal cramps; traveler’s diarrhea Food or water contaminated with feces Dehydration Treat if severe Options: trimethoprim-sulfamethoxazole, azithromycin, ciprofloxacin E. coli– enteroinvasive Fever, bloody or nonbloody diarrhea, dysentery Food or water contaminated with feces Dehydration Treat if severe Options: trimethoprim-sulfamethoxazole, azithromycin, ciprofloxacin E.

nated with feces Dehydration Treat if severe Options: trimethoprim-sulfamethoxazole, azithromycin, ciprofloxacin E. coli– enteroinvasive Fever, bloody or nonbloody diarrhea, dysentery Food or water contaminated with feces Dehydration Treat if severe Options: trimethoprim-sulfamethoxazole, azithromycin, ciprofloxacin E. coli– enteroaggregative Watery diarrhea, may be prolonged Food or water contaminated with feces Dehydration Treat if severe Options: trimethoprim-sulfamethoxazole, azithromycin, ciprofloxacin Yersinia Bloody diarrhea with mucus, fever, abdominal pain; pseudoappendicitis syndrome: fever, right lower quadrant pain, leukocytosis; Yersinia pseudotuberculosis causes fever, scarlatiniform rash, abdominal pain Contaminated food: improperly cooked pork, unpasteurized milk, untreated water; contact with animals (ungulates, rodents, rabbits, birds) Acute: bacteremia, pharyngitis, meningitis, osteomyelitis, pyomyositis, conjunctivitis, pneumonia, empyema, endocarditis, acute peritonitis, liver/ spleen abscess; convalescence: erythema nodosum, glomerulonephritis, reactive arthritis Typically self-limited; if severe, treat with trimethoprim-sulfamethoxazole, aminoglycosides, cefotaxime, fluoroquinolones, tetracycline, doxycycline, chloramphenicol Vibrio cholerae Voluminous watery diarrhea, usually without cramps or fever, classically described as “rice water” stools Travel to affected areas, consumption of contaminated water or food (particularly undercooked seafood) May rapidly lead to hypovolemic shock, hypoglycemia, hypokalemia, metabolic acidosis, seizures Treat if moderate or severe: azithromycin, doxycycline; ciprofloxacin or trimethoprimsulfamethoxazole if resistant *Most experts continue to limit fluoroquinolone use in children to those selected clinical situations where the benefits clearly outweigh the risks of therapy and there are few other antibiotic choices. TABLE 131-8 Recommendations for Measuring Glucose and Serum Electrolytes •   Moderately dehydrated children whose history and physical examination findings are inconsistent with acute gastroenteritis •   All severely dehydrated children •   All children requiring IV rehydration31 Source:  Reproduced  with permission  from Guarino  A, Albano F, Ashkenazi  S, et al: European  Society for Paediatric Gastroenterology, Hepatology, and Nutrition/European Society for Paediatric Infec tious Diseases evidence based guidelines for the management of acute gastroenteritis in children in Europe. J Paediatr Gastroenterol Nutr 46: S81, 2008. Copyright Lippincott Williams & Wilkins. Hepatology, and Nutrition recommendations for measuring electrolytes in children with gastroenteritis. In a study assessing the utility of routinely obtaining electrolytes in 182 children receiving IV rehydration,27 an electrolyte abnormality was present in nearly half, and management changed in 10% of children. All interventions were related to the administration of fluids and glucose or potassium. Although BUN is elevated in severe dehydration, it does not identify lesser degrees of dehydration very well. Serum bicarbonate>15 mEq/L makes dehydration unlikely. 28 Last, urinary indices have been demon strated to correlate poorly with severity of dehydration.29 Tintinalli_Sec12_p0669-0996.indd 846 8/2/19 7:53 PM

m. Although BUN is elevated in severe dehydration, it does not identify lesser degrees of dehydration very well. Serum bicarbonate>15 mEq/L makes dehydration unlikely. 28 Last, urinary indices have been demon strated to correlate poorly with severity of dehydration.29 Tintinalli_Sec12_p0669-0996.indd 846 8/2/19 7:53 PM CHAPTER 131: Vomiting, Diarrhea, and Dehydration in Infants and Children 847  RAPID STOOL TESTS Classic gastroenteritis of bacterial origin arises in the distal small bowel or colon to cause dysentery, with fecal blood, pus, and mucus. Most viral, parasitic, and toxin-mediated etiologies do not cause significant inflammation. Thus, tests for inflammatory markers might help differentiate between viral and bacterial gastroenteritis. Identifying fecal leukocytes has technical limitations, including the need for an experienced technician and a fresh stool sample to provide an accurate identification. More than five WBCs per high-power field has a sensitivity of 73% (95% confidence interval, 0.33% to 0.94%) and specificity of 84% (95% confidence interval, 0.50% to 0.96%) and is moderately useful for identifying bacterial gastroenteritis. 30 A marker for fecal leukocytes, fecal lactoferrin, is increased during bacterial infection and in children with clinically more severe disease, and thus it may be a good marker for predicting and monitoring intestinal inflammation in children with infectious diarrhea.  STOOL CULTURES With a diagnostic yield as low as 2% and a high cost per positive result, routine stool cultures are not necessary in acute gastroenteritis. In select instances, however, stool culture is warranted. Several high-risk factors have been identified: >10 stools in the previous 24 hours, 32,33 travel to high-risk country,32 fever,32 older age child,32 blood or mucus in stool,33,34 and abdominal pain/tenderness.33 Obtain stool cultures in cases of persistent diarrhea, when a specific antimicrobial treatment is being considered, or when infection must be excluded to support another diagnosis, such as inflammatory bowel disease. Rectal swabs are an excellent alternative to stool when enteropathogen identification and rapid detection are needed, appropriate molecular diagnostic technology is available, and a stool specimen is not immediately available. Five bacterial pathogens commonly produce gastroenteritis in North America (Table 131-7): Salmonella, Shigella, Yersinia, Campylobacter, and pathogenic E. coli. All but E. coli do not normally inhabit the alimentary tract, so their identification in stool specimens diagnoses bacterial gastroenteritis. E. coli, however, is part of the usual gut flora and is rarely pathogenic; therefore, serotyping is useful for detecting E. coli O157, which causes hemolytic-uremic syndrome. In some parts of the world, Vibrio cholerae is a common bacterial cause of gastroenteritis.  IMAGING In general, radiologic investigations play a very limited role in assessment of pediatric acute gastroenteritis. Imaging is valuable when the diagnosis is uncertain, such as may occur in children with isolated vomiting. Although plain films of the abdomen are usually nonspecific and have low sensitivity, they may be a useful starting point when looking for bowel obstructions, foreign bodies, and bowel perforation. On the other hand, in a group of neonates with bilious vomiting in the first 72 hours of life, 56% of lesions requiring surgical repair were not detected with the use of plain abdominal radiographs, reinforcing the need for further imaging when clinically indicated.

obstructions, foreign bodies, and bowel perforation. On the other hand, in a group of neonates with bilious vomiting in the first 72 hours of life, 56% of lesions requiring surgical repair were not detected with the use of plain abdominal radiographs, reinforcing the need for further imaging when clinically indicated. 36 A history of abdominal surgery or foreign body ingestion, or evidence on exam of abnormal bowel sounds, abdominal distention, or peritonitis has 93% sensitivity and 40% specificity in detecting diagnostic or suggestive radiographs in patients with major diseases potentially requiring procedural intervention. Abdominal ultrasonography has an important diagnostic role in pediatric centers, but usefulness depends upon technical expertise.  TREATMENT Oral Rehydration Therapy Treatment is directed at (1) preventing or treating dehydration, (2) replacing ongoing fluid losses, and (3) meeting nutritional needs. The worldwide adoption of oral rehydration therapy has revolutionized the treatment of dehydration. Oral rehydration therapy has reduced mortality in developing nations and is a safe and effective treatment for dehydrated children in developed nations. The physiologic effectiveness of oral rehydration therapy is based on the coupled transport of sodium and glucose molecules at the brush border of intestinal epithelial cells, which provides a gradient for the passive absorption of water. This mechanism remains relatively intact, even in severe diarrheal disease, and functions optimally when the sodium-toglucose ratio is 1:1. 26 The World Health Organization recommends an oral rehydration solution with a sodium concentration of 75 mmol/L, and it is effective for children with noncholera diarrhea as measured by reduced stool output, reduced vomiting, and a reduced need for supplemental IV therapy. 25 Most commercially available oral rehydration solution formulations in North America and Europe contain 45 to 60 mmol/L of sodium ( Table 131-9). Many other beverages traditionally suggested for children with vomiting and diarrhea, such as tea, juice, or sports drinks, are deficient in sodium and may provide excessive sugar, amplifying fluid losses. These beverages are not suitable for use as rehydration solutions but, in children with mild gastroenteritis and minimal dehydration, initiating oral hydration with dilute apple juice followed by a child’s preferred fluids, results in fewer treatment failures as compared with the use of electrolyte maintenance solutions. 38 Thus, in high-income countries, the use of dilute apple juice and preferred fluids may be an appropriate alternative to electrolyte maintenance fluids in children with mild gastroenteritis and minimal dehydration. Although oral rehydration therapy should be the first-line treatment for most children with acute gastroenteritis, it is often underused by healthcare providers in industrialized countries, who too often elect to administer IV rehydration. This may be due to misperceptions about the effectiveness of IV rehydration or unfamiliarity with published guide lines. 25,26 IV rehydration is appropriate and necessary in children with severe dehydration, hemodynamic compromise, or when altered mental status precludes safe oral administration of fluid. 26 Children with mild to moderate dehydration are candidates for oral rehydration therapy and do not need IV rehydration as first-line therapy. When comparing oral rehydration therapy with IV therapy, a Cochrane review concluded that there is no difference in failure to rehydrate, weight gain, or total fluid intake; oral rehydration therapy is associated with a shorter hospital stay. For every 25 children treated with oral rehydration therapy, one child would fail and require IV rehydration.

therapy with IV therapy, a Cochrane review concluded that there is no difference in failure to rehydrate, weight gain, or total fluid intake; oral rehydration therapy is associated with a shorter hospital stay. For every 25 children treated with oral rehydration therapy, one child would fail and require IV rehydration. 39 A sample ED algorithm incorporating oral rehydration therapy is provided in Figure 131-1. TABLE 131-9 Composition of Standard ORS, Reduced-Osmolarity WHO ORS, and Other Commonly Consumed Beverages Carbohydrate (mmol/L) Sodium (mmol/L) Potassium (mmol/L) Chloride (mmol/L) Base (mmol/L) Osmolarity (mOsm/L) WHO reduced osmolarity (2002) 75 75 20 65 10 245 Pedialyte ® 139 45 20 35 20 250 Enfalyte® (formerly Ricelyte) 167 50 25 45 34 200 Apple juice 666 0.4 44 45 N/A 730 Coca-Cola Classic® 622 1.6 N/A N/A 13.4 650 Ginger ale 500 3.5 0.1 N/A 3.6 565 Gatorade® 322 20 3 N/A 3 350 Chicken broth 44 260 0.5 260 N/A 450 Abbreviations: N/A = not available; ORS = oral rehydration solution; WHO = World Health Organization. Tintinalli_Sec12_p0669-0996.indd 847 8/2/19 7:53 PM

666 0.4 44 45 N/A 730 Coca-Cola Classic® 622 1.6 N/A N/A 13.4 650 Ginger ale 500 3.5 0.1 N/A 3.6 565 Gatorade® 322 20 3 N/A 3 350 Chicken broth 44 260 0.5 260 N/A 450 Abbreviations: N/A = not available; ORS = oral rehydration solution; WHO = World Health Organization. Tintinalli_Sec12_p0669-0996.indd 847 8/2/19 7:53 PM 848 SECTION 12: Pediatrics Clinical dehydration score Include: age >2 months with presumed gastroenteritis Exclude: • Toxic appearance or ICU required • Diarrhea >7 days • Significant comorbidity (e.g., diabetes, metabolic disorder s, chronic GI illness) Continue with child's preferred, usual, and ageappropriate diet If vomiting, offer frequent small feedings No other medications Provide discharge teaching Discharge to home If persistent vomiting or refusing oral intake due to nausea, consider ondansetron (if given, wait 15 minutes before resuming ORT) 1. Sufficient oral intake f or losses? 2. Clinical dehydration score impr oved? Clinical assessment of dehydration status Guideline eligible? Not guideline eligible Treat according to patient-specific clinical condition Triage RN to start ORT ORS, start at 5 mL every 5 minutes Patient placed in room Continue ORT Aim for 25–50 mL/kg over 1–2 hours Treat emergently as indicated for hypovolemic shock When stable, begin ORT Discuss options with family 1. Continue ORT Reassess child every 60 minutes 2. IV fluids Consider discharging home None/minimal dehydration Severe dehydration Some dehydration Reassess in 1 hour Yes No improvement Improved Yes IV*ORT (PO or NG) Reassess 60 minutes laterFIGURE 131-1. Algorithm for evaluation and management of acute gastroenteritis in children >2 months of age based on clinical assessment of dehydration status. ORT = Oral rehydra tion therapy. *If IV access is difficult, consider nasogastric (NG) oral rehydration solution (50 mL/kg) over 3 hours instead. Continue oral rehydration therapy (ORT) during IV therapy. ICU = intensive care unit; ORS = oral rehydration solution; RN = registered nurse. In children with moderate dehydration undergoing oral rehydration therapy, the fluid deficit should be corrected rapidly (over 4 hours). Give 50 to 100 mL of oral rehydration solution per kilogram of body weight, plus additional oral rehydration solution to compensate for ongoing losses (approximately 10 mL/kg per stool and 2 mL/kg per emesis). Offer small volumes initially, such as 5 mL every 2 to 5 minutes, and increase as tolerated. A general rule is to aim for about 1 ounce (30 mL) of oral rehydration solution per kilogram of body weight per hour. Do not limit breastfeeding during any phase of oral rehydra tion therapy, both for the nutritional support of the infant and to avoid a decrease in the mother’s milk supply. If necessary, oral rehydration solution may be provided as a supplement. When oral rehydration is not feasible, enteral rehydration by the nasogastric route provides an effective alternative to IV rehydration . This method allows for rehydration at a steady rate and is as successful as, and more cost effective than, IV rehydration. 40 Children with severe dehydration requiring IV rehydration can begin oral rehydration therapy when perfusion and mental status return to normal. Caregivers should understand the technique and rationale of oral rehydration therapy and should be provided with helpful equipment such as a clock and a syringe or dropper. Recognizing caregiver expectations and addressing potential obstacles, such as misconceptions about oral rehydration therapy or exhaustion, may also contribute to a successful outcome. IV Hydration Parenteral therapy is discussed in Chapter 132, “Fluid and Electrolyte Therapy in Infants and Children.

yringe or dropper. Recognizing caregiver expectations and addressing potential obstacles, such as misconceptions about oral rehydration therapy or exhaustion, may also contribute to a successful outcome. IV Hydration Parenteral therapy is discussed in Chapter 132, “Fluid and Electrolyte Therapy in Infants and Children. ” Antiemetics Although vomiting is not a contraindication to oral rehydration therapy and does not usually preclude successful oral rehydra tion, the presence of ongoing vomiting may be an obstacle to initiating or continuing oral rehydration therapy. Ondansetron, a 5-hydroxytryptamine (serotonin) receptor antagonist, may be used as an adjunct to oral rehydration therapy in children with persistent vomiting at a dose of 0.15 milligram/kg/dose PO. The use of intravenous ondan setron and multiple dose therapy is not supported by the evidence, Tintinalli_Sec12_p0669-0996.indd 848 8/2/19 7:53 PM

yptamine (serotonin) receptor antagonist, may be used as an adjunct to oral rehydration therapy in children with persistent vomiting at a dose of 0.15 milligram/kg/dose PO. The use of intravenous ondan setron and multiple dose therapy is not supported by the evidence, Tintinalli_Sec12_p0669-0996.indd 848 8/2/19 7:53 PM CHAPTER 131: Vomiting, Diarrhea, and Dehydration in Infants and Children 849 which associates both such approaches with increased side effects 41 and no additional benefit beyond a single oral dose. 42 Do not use dopamine receptor agonists (such as promethazine, prochlorperazine, metoclopramide, and droperidol) to treat vomit ing in children because of the potential for respiratory depression and extrapyramidal reactions. 43 In addition, they lack evidence of efficacy. The U.S. Food and Drug Administration issued an alert in 2006 indicating that promethazine (marketed as Phenergan ® ) should not be used in children <2 years of age because of the potential for fatal respiratory depression. Maintenance Phase and Diet For children with minimal or no dehydration and those who have been successfully rehydrated, the priority is to prevent dehydration by providing maintenance fluid needs and replacing losses. Fluid needs may be met with oral rehydration solution or regular diet. Children undergoing oral rehydration therapy should resume feedings with an age-appropriate, palatable, and nutritionally complete diet as soon as the initial fluid deficit has been replaced. Do not withhold feedings for >4 hours in a dehydrated child or for any length of time in a child who is not dehydrated. Early refeeding dur ing oral rehydration therapy has clinical and nutritional benefits and is supported in major guidelines. 25,26 The introduction of full-strength formula or regular diet immediately after rehydration is associated with increased weight gain and does not limit the success of oral rehydration therapy. Most young children can continue to receive lactose-containing milk or formula. However, there does appear to be a slight reduc tion in the duration of diarrhea and the treatment failure rate among inpatients administered lactose-free products, and this approach may be considered in this patient population. The banana, rice, applesauce, and toast diet is unnecessarily restric tive and may not provide enough nutrition, so it is no longer recommended. 26 Because fats are an important source of calories, low-fat diets are discouraged. Antidiarrheal Medications Antidiarrheal medications are not rec ommended either due to safety concerns or a lack of data to sup port effectiveness. Potential risks outweigh benefits. Loperamide, a peripheral opiate receptor agonist that can reduce diarrhea, is absolutely contraindicated in children <2 years old and for those with bloody stools or suspected bacterial gastroenteritis from Salmonella, Shigella, or Campylobacter. The drug can cause lethargy and paralytic ileus. Additionally, loperamide may be associated with a possible increased risk of hemolytic-uremic syndrome when used in the setting of enterohemorrhagic E. coli infection. Although older children with viral gastroenteritis who take an age-appropriate dose are unlikely to experience serious events, potential risks likely outweigh benefits in most children. Adsorbents and Antisecretory Agents Smectite is an aluminomagnesium silicate that binds some toxins, bacteria, and viruses and is used in several European countries as an antidiarrheal agent. Although some trials and a recent meta-analysis have reported effectiveness in reducing diarrhea, the limitations of the studies prevent any firm conclusions from being drawn. Bismuth subsalicylate is an antisecretory agent that is commonly found in over-the-counter diarrhea medications.

ries as an antidiarrheal agent. Although some trials and a recent meta-analysis have reported effectiveness in reducing diarrhea, the limitations of the studies prevent any firm conclusions from being drawn. Bismuth subsalicylate is an antisecretory agent that is commonly found in over-the-counter diarrhea medications. Although bismuth has a modest effect on reducing severity of diarrhea, it can cause elevated salicylate levels in children. 45 Consequently, products containing bismuth subsalicylate (e.g., Pepto-bismol Ø , KaopectateØ ) should not exceed dosing recommendations in children less than 12 years of age. Racecadotril is a prodrug that must be hydrolyzed to its active metabolite (thiorphan), which then acts as an enkephalinase inhibitor that decreases intestinal secretion by preventing the breakdown of endogenous GI opioids. It is available in Europe and Southeast Asia, but not in the United States. In a systematic review including nine trials and 1384 children, twice as many patients had diarrhea resolution at any time point when administered racecadotril relative to placebo. 46 Although racecadotril reduces stool frequency (stool ratio of racecadotril to placebo = 0.63), it does not decrease major clinical outcomes such as hospitalization. Probiotics Probiotics are living organisms that, when ingested, can modulate mucosal and systemic immunity by altering microbial bal ance in the intestinal tract. Y ogurt is a dietary source of probiotics, though the quantity of bacteria in yogurt is variable. Data from several meta-analyses show a moderate clinical benefit of certain probiotic strains in reducing the duration and/or volume of diarrhea in hospi talized children. While a sizable and growing number of patients are prescribed probiotics to treat intestinal infections, 48,49 only five of 12 AGE management guidelines summarized in a recent review 50 endorse probiotic use. Most published studies suffer from methodologic limita tions, including small sample sizes, use of restricted populations, limited knowledge of causative pathogens, and an absence of adverse event reporting. 51 The first pediatric ED study to date that evaluated Lactoba cillus rhamnosus GG reported no reduction in the time to normal stool or the number of diarrheal stools.52 Two recently completed multicenter prospective randomized trials of probiotics for acute pediatric gastroenteritis presenting to the emergency department both failed to demonstrate any benefit among more than 1500 combined study participants, suggesting no role for probiotics in this population. 53,54 Lastly, there is some evidence that many probiotic product labels do not adequately identify or quantify microbes and that when tested some products do not match their labeled microbiologic specification. Prebiotics, which are nondigestible food components believed to improve microbial balance in the intestinal tract, have not been exten sively studied and are not recommended. There is no high-quality published evidence regarding the use of homeopathic or herbal medications for the management of gastroenteritis. Zinc Zinc is necessary for intestinal mucosal healing, and its deficiency has been associated with increased diarrhea severity. Malnourished children >6 months old benefit the most from zinc therapy (27-hour reduction in diarrhea duration), and its use should likely be limited to such groups of children.

stroenteritis. Zinc Zinc is necessary for intestinal mucosal healing, and its deficiency has been associated with increased diarrhea severity. Malnourished children >6 months old benefit the most from zinc therapy (27-hour reduction in diarrhea duration), and its use should likely be limited to such groups of children. 56 Because zinc is an effective therapy for diarrhea and reduces morbidity and mortality in the setting of low-income countries, 57 the United Nations Children’s Fund and the World Health Organization recommend zinc supplementation as a universal treatment for children with diarrhea in low-income countries at a dose of 20 milligrams/d of any zinc salt orally for 10 to 14 days (10 milligrams/d for infants <6 months old). Antibiotics for Acute Gastroenteritis Because the cause of gastro enteritis is rarely known upon presentation, treatment decisions must be made before the identification of a pathogen is possible. Because the vast majority of episodes of pediatric gastroenteritis are of viral origin, do not routinely give antibiotics. In select clinical circumstances, antibiotics may be indicated; see recommendations for specific patho gens and clinical settings in Table 131-7. In most instances, however, antibiotics should only be provided to extremely unwell (e.g., septic or bacteremic), extremely young, or immunocompromised children. When required, the choice of antimicrobial agent depends on local prevalence and resistance patterns. Parenteral rather than oral antibiotic therapy is appropriate for patients unable to take oral medications, patients with toxic appearance or underlying immunodeficiency, and febrile infants <3 months of age. Children with watery diarrhea generally should not receive empiric antibiotics unless they have been exposed to cholera. Antibiotics are effective in reducing the symptoms and infectivity of Shigella gastroenteritis. Because of increasing resistance, use ampicillin or trimethoprim-sulfamethoxazole only if the strain is susceptible. Otherwise, azithromycin is an appropriate first-line agent. Ceftriaxone is the treatment of choice for parenteral therapy. Do not use antibiotics to treat Salmonella gastroenteritis unless spe cific risk factors are present. A Cochrane review (12 trials, 767 patients) demonstrated no evidence of benefit from antibiotic therapy in other wise healthy individuals with nontyphoidal Salmonella gastroenteritis. Although the number of young children studied was small, adverse events were more common in participants who received antibiotic treatment. Thus, antibiotics should only be administered to high-risk children to reduce the risk of Salmonella bacteremia and extraintestinal infections. High-risk children include those with underlying immune deficiencies, sickle cell disease, immunosuppressive therapy, or inflam matory bowel disease and infants <3 months old. Antibiotic therapy for Campylobacter gastroenteritis has a modest effect on symptoms and is most effective if treatment is started within 3 days of disease onset. 59 Antibiotics reduce the duration of fecal excretion of organisms and are recommended to reduce transmission in day care centers and institutions. Tintinalli_Sec12_p0669-0996.indd 849 8/2/19 7:53 PM

oenteritis has a modest effect on symptoms and is most effective if treatment is started within 3 days of disease onset. 59 Antibiotics reduce the duration of fecal excretion of organisms and are recommended to reduce transmission in day care centers and institutions. Tintinalli_Sec12_p0669-0996.indd 849 8/2/19 7:53 PM 850 SECTION 12: Pediatrics Antibiotics for Shiga toxin–producing E. coli do not significantly affect the clinical course. Importantly, in children with Shiga toxin–producing E. coli infection, there is a significant association between anti biotic use and the risk of developing the hemolytic-uremic syndrome. 60 Therefore, children with E. coli O157:H7 should not receive antibiotics. Intravenous volume expansion is an underused intervention that may decrease the frequency of oligoanuric renal failure in children with diarrhea-associated hemolytic-uremic syndrome (hematocrit <30% with evidence of intravascular erythrocyte destruction), thrombocyto penia (platelet count <150 × 10 3/mm3), and impaired renal function. 13 Antibiotics may be useful for severe forms of enteroinvasive, enteropathogenic, or enterotoxigenic E. coli infection. Azithromycin and trimethoprim-sulfamethoxazole are treatment options. Antibiotics reduce the severity of V . cholerae diarrhea. Treatment options include doxycycline, azithromycin, or trimethoprim-sulfamethoxazole. Antimicrobial treatment of Yersinia species is appropriate if severe disease, bacteremia, or extraintestinal infection is suspected. Options include trimethoprim-sulfamethoxazole, aminoglycosides, cefotaxime, fluoroquinolones, tetracycline, doxycycline, and chloramphenicol.  DISPOSITION AND FOLLOW-UP There are no established evidence-based criteria for admission of patients with gastroenteritis. In general, well-appearing children with minimal or no dehydration who are able to receive oral rehydration therapy at home should be discharged, and caregivers should be taught how to administer oral rehydration therapy and recognize signs of dehydration. Discharge instructions should be verbal and written. Sample discharge instructions are presented in Table 131-10. Ideally, caregivers will have had the opportunity to practice oral rehydration therapy and ask questions while in the ED. Children with moderate or severe dehy dration, intractable or bilious vomiting, a suspected surgical condition, or significant laboratory or neurologic abnormalities, including lethargy or seizures, require further testing and should be observed in the ED or admitted. Patients not likely to succeed with home oral rehydration therapy, such as those with large ongoing losses or inadequate support, should also be observed or admitted. Many patients with dehydration who require ongoing treatment can be successfully managed in an observation unit. 56 Y oung infants are at risk for more rapid and severe dehydration, so the threshold for admission should be low, and followup in 24 hours should be ensured if discharge is considered. Families who are discharged should be instructed to return to seek further care if their child becomes unable to receive oral rehydration therapy, has persistent or bilious emesis, or shows increasing evidence of dehydration, or if symptoms are worsening. SPECIAL SITUATIONS  DIARRHEA WITH OR WITHOUT VOMITING Adverse Food Reactions Adverse food reactions can be due to either an adverse immunologic response, otherwise known as an allergy, or an adverse physiologic response, often referred to as food intolerance. 61 The National Institute of Allergy and Infectious Diseases recognizes four categories of immune-mediated adverse food reactions: immunoglobin E (IgE)-mediated, non–IgE-mediated, mixed, and cell-mediated.

esponse, otherwise known as an allergy, or an adverse physiologic response, often referred to as food intolerance. 61 The National Institute of Allergy and Infectious Diseases recognizes four categories of immune-mediated adverse food reactions: immunoglobin E (IgE)-mediated, non–IgE-mediated, mixed, and cell-mediated. 62 IgEmediated GI allergic symptoms may consist of nausea, abdominal pain, cramping, vomiting, or diarrhea developing within minutes to 2 hours of the ingestion of a food allergen. GI symptoms are often accompanied by symptoms involving the mouth or skin and may also include respiratory and systemic manifestations. Eosinophilic esophagitis and gastroenteritis are examples of a mixed IgE and non-IgE food allergy, with T-cell– mediated responses playing a significant role in pathogenesis. 63 Patients may present at any age, and many will have other allergic or atopic conditions. The portion of the GI tract involved determines symptoms. Because symptoms tend to be delayed, identifying the offending food(s) may be challenging. Infants often present with feeding difficulties, gas troesophageal reflux, vomiting, and failure to thrive. Older children may present with vomiting, abdominal pain, or symptoms similar to irritable bowel syndrome. A history of dysphagia or food impactions suggests eosinophilic esophagitis. Non–IgE-mediated food allergies are primarily T-cell–mediated and tend to result in delayed symptoms. Examples include food pro tein–induced enterocolitis syndrome, food protein–induced allergic proctocolitis, and celiac disease. 63 Food protein–induced enterocolitis syndrome is a potentially severe condition with a peak incidence in infants between 0 and 9 months old. Proteins in cow’s milk or soy for mulas are the most common triggers in infants, and symptoms consist of profuse vomiting and diarrhea for several hours after exposure, at times resulting in shock. Many other foods have been implicated in food TABLE 131-10 Sample Gastroenteritis Discharge Instructions Your child has been diagnosed with gastroenteritis. Gastroenteritis is an illness that consists of vomiting and diarrhea. It is often caused by viruses and usually can be treated without medications. Preventing dehydration is the most important goal in caring for children with gastroenteritis. How will I know if my child is becoming dehydrated? •   Dry lips and mouth. •   Decreased activity level. •   Sunken eyes. •   Sunken fontanelle (soft spot) in babies <1 y. •   Not urinating as often as usual or dark urine. •   Reduced tears when crying. What should I give my child to eat and drink? •   Children who do not have signs of dehydration can drink what is usual for them. You do not need to stop giving milk. Drinks with a lot of sugar, such as fruit juices, can make diarrhea worse. •   Your child should return to his or her normal diet as soon as possible. A special diet is not necessary. Good nutrition is important, even if there is still vomiting or diarrhea. •   If you are breastfeeding, continue breastfeeding. Babies taking formula can continue to receive their usual formula. •   Children who are showing some signs of dehydration should receive oral rehydration solutions (see below). What types of fluids are acceptable for oral rehydration? •   Over-the-counter rehydration solutions are ideal for rehydration. Some brands include Pedialyte and Enfalyte. Generic solutions are also available. Flavored solutions are usually preferred by children. •   Sports drinks are not the same as oral rehydration solutions and should not be used in infants or children who are dehydrated. They may be acceptable in older children with minimal dehydration. •   Plain water and tea do not have sugar or salt and can cause electrolyte changes, especially if given to small babies.

•   Sports drinks are not the same as oral rehydration solutions and should not be used in infants or children who are dehydrated. They may be acceptable in older children with minimal dehydration. •   Plain water and tea do not have sugar or salt and can cause electrolyte changes, especially if given to small babies. •   Soda/pop and juices have too much sugar and not enough salt to be used for oral rehydration. •   Children who are not dehydrated do not need a special oral rehydration solution. How do I give oral rehydration? •   If your child is vomiting, start with small amounts of oral rehydration fluid, such as one teaspoon (5 mL) every 5 min. Increase the amount gradually, as tolerated. •   If your child is breastfed, continue breastfeeding. Oral rehydration solutions can supplement breast milk after or between breast feedings, but should never take the place of breast milk. When should I call my child’s doctor or seek help? •   Call your doctor immediately or go to the nearest emergency department if: •   Your child seems dehydrated and is not able to drink. •   Your child’s vomit is green or bloody. •   Your child has severe abdominal pain. •   Your child appears to be very sick. •   Your child has blood in the diarrhea. •   Your child has a fever and is <3 mo of age. When should I follow up with my child’s doctor? •   If your child is <6 mo of age, follow up within 24–48 h. •   If your child is >6 mo of age, call your doctor’s office and schedule a follow-up if symptoms continue. Tintinalli_Sec12_p0669-0996.indd 850 8/2/19 7:53 PM