Vomiting may suggest mucosal disease of the gastrointestinal tract, such as inﬂammatory bowel disease Fever: if persistent (>72 hours), if child appears ill, or if in an infant younger

VomitingKalyan Ray Parashette, MD,*

Joseph Croffie, MD, MPH†

Author Disclosure

Drs Parashette and

Croffie have disclosed

no financial

relationships relevant

to this article. This

commentary does not

contain discussion of

unapproved/

investigative use of

a commercial product/

device.

Practice Gap

Clinicians must be cognizant of the common, more benign but often treatable causes of

vomiting as well as the less common but life-threatening surgical, metabolic and infec-

tious disorders of which vomiting is a symptom. Practitioners should stay abreast of

evolving recommendations on newer, effective anti-emetic therapies for treating chemo-

therapy patients and others with non-cancerous disorders.

Objectives After completing this article, readers should be able to:

1. Know the causes of vomiting in children of different age groups.

2. Distinguish between nonorganic and organic causes of vomiting.

3. Diagnose and treat eosinophilic esophagitis (EE).

4. Develop an initial management plan for a child with intestinal obstruction.

5. Evaluate and manage rumination syndrome and cyclic vomiting syndrome (CVS) in

children.

6. Understand the role of various antiemetic medications in the treatment of vomiting in

children.

DefinitionsWewill use the following terms as defined by the American Gastroenterological Association(AGA). (1)

• Vomiting: Forceful oral expulsion of gastric contents associated with contraction of theabdominal and chest wall musculature.

• Nausea: The unpleasant sensation of the imminent need to vomit, usually referred to thethroat or epigastrium; a sensation that may or may not ultimately lead to the act ofvomiting.

• Regurgitation: The act by which food is brought back into the mouth without the ab-dominal and diaphragmatic muscular activity that characterizes vomiting.

• Retching: Spasmodic respiratory movements against a closed glottis with contractions ofthe abdominal musculature without expulsion of any gastric contents, referred to as “dry

heaves.”• Rumination: Chewing and swallowing of regurgitated

food that has come back into the mouth through a volun-tary increase in abdominal pressure within minutes of eat-ing or during eating.

PathophysiologyVomiting is a complex process that involves various systemsthat influence the vomiting center (Fig 1). The vomitingcenter is located in the lateral medullary reticular formationof the brainstem and is the final pathway for the physiologic

Abbreviations

AGA: American Gastroenterological AssociationCVS: cyclic vomiting syndromeEE: eosinophilic esophagitisGER: gastroesophageal refluxGERD: gastroesophageal reflux diseaseGI: gastrointestinalPPI: proton pump inhibitor

*Pediatric Gastroenterology and Hepatology Fellow, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Riley

Hospital for Children, Indiana University School of Medicine, Indianapolis, IN.†Professor of Clinical Pediatrics, Director, Pediatric Gastrointestinal Motility Laboratory, Riley Hospital for Children, Division of

Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children, Indiana University School of Medicine,

Indianapolis, IN.

Article gastrointestinal disorders

Pediatrics in Review Vol.34 No.7 July 2013 307

processes that result in vomiting. The center has predom-inantly muscarinic M1 (M1), histamine 1 (H1), neuroki-nin 1, and serotonin receptors. The vomiting centerreceives input from 4 distinct centers: chemoreceptortrigger zone, vagal afferent system, vestibular system,and high cortical centers.

The chemoreceptor trigger zone, also known as areapostrema, is located at the caudal portion of the fourthventricle. The zone is located outside the blood brainbarrier and serves as the emetic chemoreceptor for thevomiting center; thus, it is influenced by triggers of vom-iting in the blood or cerebrospinal fluid. The centermainly has dopamine 2 (D2) receptors. Other involvedreceptors are M1- and H1-receptors.

Vagal Afferent SystemThe vagal afferent system primarily receives input fromthe GI tract and is activated by distention or irritationof the GI tract from various causes. It is mediated by se-rotonin receptors.

Vestibular SystemThe vestibular system is involved in the vomiting associ-ated with motion sickness and labyrinthine disorders. It ismediated via M1- and H1-receptors.

Higher Cortical CentersThis pathway is not well understood. This system may beinvolved in other nonanatomical causes of vomiting, such

as stress-induced vomiting and vomiting that results frombehavioral or psychiatric disorders. Conduction pathwaysbetween the higher and the lower centers of the brain en-able constant communication and interaction betweenthe 2 regions.

The act of vomiting has multiple phases: a preejectionphase, a retching phase, and an ejection phase. In thepreejection phase, gastric relaxation and retroperistalsisoccur. In the retching phase, rhythmic contractions ofrespiratory, abdominal wall, intercostal, and diaphragmmuscles occur against a closed glottis. In the finalphase, intense contraction of the abdominal musclescombined with relaxation of the pharyngoesophagealsphincter results in ejection. Vomiting can also occurabruptly without the preejection and retching phases;such vomiting is often forceful and is referred to as pro-jectile vomiting, which is seen in cases of gastric outletobstruction.

Differential Diagnosis of VomitingVomiting is a symptom with a wide differential diagnosis,ranging from lesions of the GI tract to systemic illnesses.A detailed history, including dietary history, review of sys-tems, family history, medication history, medical history,and surgical history, is important in the initial evaluationto identify a cause.

Acute onset of vomiting with severe abdominal painmay suggest a surgical origin; common associated symp-toms include localized or generalized abdominal tender-ness, signs of peritonitis, and absent or hyperactive bowelsounds. When vomiting is chronic, identifying the pat-tern of vomiting often provides clues to the diagnosis.

Vomiting is often characterized as nonbilious, bilious,or bloody based on the content. Vomitus from the esoph-agus, stomach, and first part of the duodenum usuallyconsists of ingested food and is clear or yellow. Biliousvomiting denotes the presence of bile and appears lightgreen to dark green. Bilious vomiting suggests obstruc-tion of the intestine beyond the ampulla of Vater untilproven otherwise. Hematemesis is the presence of bloodin the vomitus. The presence of bright red blood in eme-sis or gastric lavage indicates active upper GI tract bleed-ing that may require immediate attention. The presenceof coffee-ground material in the vomitus indicates thatblood has been acted on by gastric acid. Vomiting is oftendescribed as projectile or nonprojectile. Projectile vomit-ing is commonly seen in gastric outlet obstruction, suchas pyloric stenosis, and in conditions that result in raisedintracranial pressure. However, this expression is com-monly misused by parents. Table 1 lists several red flags

Figure 1. Pathophysiology of vomiting. The figure demon-strates various systems that influence the vomiting center.

gastrointestinal disorders vomiting

308 Pediatrics in Review Vol.34 No.7 July 2013

that should alert one to look for an organic cause in a pa-tient who presents with vomiting, Table 2 provides a listof differential diagnoses based on individual organ sys-tems, and Table 3 lists potential causes of vomiting basedon age at presentation.

Common Causes of Emesis in InfancyGER and GERD

Gastroesophageal reflux (GER) is the passage of stomachcontents into the esophagus and can be a normal physi-ologic process. It is common in healthy term infants,children, and adults. Regurgitation is often used inter-changeably with GER. It is the effortless and nonprojec-tile passage of stomach contents into the oropharynx. Ifa large volume of stomach contents exit the mouth withforce, it may be erroneously labeled as projectile vomitingby the family. Infantile regurgitation peaks at 3 to 4months (67% of infants), gradually decreases to 14% at7 months, and decreases to less than 5% by 12 to 14months. (2) Common symptoms associated with thisare feeding refusal, irritability, fussiness, cough, apnea,and wheezing. Given that regurgitation is commonlytransient, esophageal injury is rarely seen on endoscopyin infants. The presence of an appropriate weight forage is a good marker suggestive of a “happy spitter”who does not warrant additional investigation. Parentaleducation about the natural course of infantile gastro-esophageal reflux is the key to successful management.Symptoms resolve in most infants by 12 months ofage. If symptoms persist past 18 months of age the childwarrants an evaluation. (3)

Gastroesophageal reflux disease (GERD) is when thepassage of stomach contents into the esophagus causesadverse symptoms or complications.

InvestigationBARIUM STUDY OF THE UPPER GI TRACT. A barium

study of the upper GI tract is not useful for diagnos-ing GERD but is primarily used to rule out anatomical ab-normalities of the upper GI tract, which may cause emesis.

SCINTIGRAPHY. A gastroesophageal scintiscan, likea barium study of the upper GI tract, is not useful to di-agnose GERD but may diagnose delayed gastric empty-ing, which could be contributing to vomiting.

ESOPHAGEAL PH MONITORING. Esophageal pH mon-itoring is not indicated to establish the diagnosis ofuncomplicated GER, but in cases of complicated gas-troesophageal reflux, it may help to establish the diagnosisand severity of GER and correlate symptoms with reflux. Itallows an extended monitoring of esophageal pH for 18 to48 hours. A reflux index (the percentage of the study pe-riod when esophageal pH was less than 4) and a symptomindex (the percentage of a reported symptom, such as ap-nea, bradycardia, and wheezing) that correlated with GERcan be calculated. In addition, information on the durationof prolonged episodes of acid reflux is useful. However,there is no correlation between acid reflux severity and in-fant symptom severity.

Esophageal pH monitoring with impedance monitor-ing is used to detect acid and nonacid reflux. It is

Table 1. Distinguishing Features of Organic Causes of Vomiting “RedFlags” That Suggest Serious Underlying ConditionsPoor weight gain or weight loss: may suggest chronicdisease, such as inflammatory bowel disease, celiacdisease, or metabolic disease

Localized abdominal pain: less likely to be functional(eg, localized right upper quadrant pain may suggestgallbladder disease, whereas localized epigastric painmay suggest esophagitis)

Bilious emesis: may be indicative of postampullaryobstruction

Severe dehydration: suggests severe vomiting andwarrants exclusion of serious underlying conditions,such as obstruction

Hematemesis: may suggest esophagitis, gastritis, orpeptic ulcer disease

Nocturnal vomiting: may suggest conditions such asgastroesophageal reflux disease or postnasal drainage

Early morning headache: may suggest increasedintracranial pressure

Short stature: may suggest conditions such asinflammatory bowel disease, hypothyroidism, or celiacdisease

Hematochezia/melena: may suggest mucosal disease ofthe gastrointestinal tract, such as inflammatory boweldisease

Fever: if persistent (>72 hours), if child appears ill, or ifin an infant younger than 6 months may be due toserious bacterial infection



commonly used to determine whether there is a correla-tion between acid and nonacid reflux and extraesopha-geal symptoms, such as apnea, bradycardia, hypoxia,and asthma. Normal values for nonacid reflux are not wellestablished in children.

ENDOSCOPY. Endoscopy is considered if a patient’ssymptoms persist or fail to respond to conservative med-ical management. An endoscopic biopsy is helpful in di-agnosing esophagitis, gastritis, or duodenitis, as well asspecifically ruling out EE.

TreatmentParental education and support are important in themanagement of GER and GERD. The anticipatoryguidance should emphasize the benign nature and dis-cuss the natural history of infantile GER, with a peak in-cidence at 4 months and resolution in most infants by 12to 18 months. Educational materials should stress that

most infants do well with conservative management, in-cluding feeding modification (avoidance of overfeeding)and positioning, in the absence of red flags. In uncom-plicated GER no testing is required, and the goal is toimprove symptoms. Milk protein intolerance can mimicGER; therefore, in an infant with poor weight gainor feeding refusal, GER, and/or extreme fussiness,a 2- to 4-week trial of a hypoallergenic formula is appro-priate as initial treatment. In breastfed infants, the effi-cacy of elimination of cow milk protein in the mother’sdiet is controversial but may be considered. Thickeningfeeds decreases observed regurgitation but not the re-flux index or reflux height. (4) It appears to reduce irrita-bility and is beneficial in an infant with poor weight gainbecause it provides extra calories. Elevation of the headof the crib, although commonly recommended, has notbeen found to improve reflux symptoms. Prone positiondecreases reflux because the esophagus enters the stomachposteriorly; however, the risk of sudden infant death

Table 2. Differential Diagnosis of Emesis by System

Gastrointestinal disorders Metabolic disorders

• Esophagus: gastroesophageal reflux, eosinophilic esophagitis,achalasia, esophageal atresia, stricture, web, ring, foreign body

• Carbohydrate: galactosemia, hereditary fructoseintolerance, pyruvate carboxylase deficiency

• Stomach: gastroenteritis, gastritis, peptic ulcer disease, pyloricstenosis, gastroparesis, bezoar

• Organic acid: phenylketonuria, urea cycle defect,maple syrup urine, tyrosinemia type 1

• Small intestine: malrotation, atresia, duplication, intussusception,volvulus, ileus, pseudoobstruction, necrotizing enterocolitis, celiacdisease, Crohn’s disease, duodenal hematoma, superior mesentericartery syndrome, milk protein enteropathy

• Fatty acid oxidation defect: carnitine deficiency,MCAD, LCAD

• Colon: Hirschsprung disease, ulcerative colitis, appendicitis,constipation, hernia

• Lysosomal storage: mucopolysaccharidoses,Niemann-Pick disease, Wolman disease

• Liver: hepatitis, acute liver failure, hepatic abscess • Peroxisomal disorders: Zellweger disease, infantileRefsum disease, acyl-CoA oxidase deficiency,adrenal leukodystrophy

• Gallbladder: cholecystitis, cholelithiasis, choledocholithiasis,gallbladder dyskinesia, choledochal cyst

• Pancreas: pancreatitis, annular pancreas, pancreatic divisum• Peritoneum: peritonitis, peritoneal adhesion Endocrine disorders

• Diabetic ketoacidosis, adrenal insufficiency/adrenalcrisis, hyperparathyroidism, pregnancy

Renal disorders Neurologic disorders• Renal tubular acidosis, ureteropelvic junction obstruction,nephrolithiasis, renal insufficiency, uremia, hydronephrosis

• Hydrocephalus, tumor, intracranial bleeding(subdural hematoma), meningoencephalitis,abscess, seizure, migraine, pseudotumor cerebri,motion sickness, ventriculoperitoneal shunt failureor infection

Infectious disorders Toxins and medications:• Urinary tract infection, meningitis, pharyngitis,sinusitis, otitis media, pneumonia, sepsis

• Aspirin, iron, lead, digoxin, alcohol, marijuana,chemotherapeutic agent

Other• Eating disorders (anorexia, bulimia), cyclicvomiting syndrome, rumination, overfeeding,psychogenic

LCAD¼long chain acyl-CoA dehydrogenase; MCAD¼medium chain acyl-CoA dehydrogenase.



syndrome outweighs the benefit. Thus, infants need tocontinue to be in a supine position during sleep. A semisu-pine position increases reflux; left side positioning may im-prove reflux symptoms but may also be associated with anincreased risk for SIDS. Infants can be prone while awakeand under direct observation.

In uncomplicated GER, acid blockers are not benefi-cial and not recommended; parental education, reassur-ance, and anticipatory guidance are recommended butnot always easily accepted. If an infant has complicatedGER, such as feeding refusal, poor weight gain, and noimprovement on dietary modification, a trial of oncedaily proton pump inhibitors (PPIs) is preferred. AnH2-blocker also may be used, although tachyphylaxismay develop with long-term H2-blocker use. Infantswith biopsy-proven reflux esophagitis require PPI treat-ment. All PPIs are equally effective. (Esomeprazole isapproved by the US Food and Drug Administrationfor erosive esophagitis in infants). Prokinetic agents,such as erythromycin and metoclopramide, have alimited role in the management of GER but may be

beneficial if delayed gastric emptying is documented.Baclofen to decrease spontaneous relaxation of thelower esophageal sphincter is the newest treatment,but this is an off-label use of this medication, and useshould be restricted.

Pyloric StenosisPyloric stenosis occurs in 2 to 3 infants per 1000 livebirths. It occurs much more commonly in males, witha male-female ratio of 4:1 to 6:1. Up to one-third of casesof pyloric stenosis are seen in first-born infants. Geneticfactors play a role in pyloric stenosis; studies show thata maternal history of pyloric stenosis is a risk factor fordevelopment of pyloric stenosis in offspring (20% ofmales and 10% of females). Also among twins, the riskfor pyloric stenosis is higher in monozygotic twins com-pared with dizygotic twins. A defect in the NOS1 geneloci, resulting in decreased neuronal nitric oxide, hasbeen implicated in the development of pyloric stenosis.Use of erythromycin in infants, especially within the firstweeks of life, is a well-established risk factor for

Table 3. Age-Related Differential Diagnosis of Emesis

Neonate (<1 month) Infant (>1-12 months)Toddler(>1-4 years) Child (4-12 years)

Teenager(13-19 years)

• GER or GERD • GER or GERD • Gastroenteritis • Gastroenteritis • Gastroenteritis• Feeding intolerance • Acute otitis media • Urinary tract

infection• Pharyngitis • Peptic ulcer

disease• Pyloric stenosis • Protein intolerance • Pharyngitis • Post infectious

gastroparesis• Cyclic vomiting

• Meconium ileus • Gastroenteritis • GERD • Eosinophilicesophagitis

• Eosinophilicesophagitis

• Congenital atresiaor webs

• Pyloric stenosis • Eosinophilicesophagitis

• Appendicitis • Pregnancy

• Malrotation withmidgut volvulus

• Intussusception • Celiac disease • Celiac disease • Poisoning/toxicingestion

• Necrotizingenterocolitis

• UTI • Intracraniallesion

• Pancreatitis • Migraine

• Metabolic disorders • Malrotation withmidgut volvulus

• Malrotation • IBD • Diabeticketoacidosis

• Hirschsprung disease • Intracranial lesion • Poisoning/toxicingestion

• Trauma (duodenalhematoma)

• Ruminationsyndrome

• Protein intolerance • Metabolic disorders • Adrenalinsufficiency

• Poisoning/toxicingestion

• Drug abuse

• Infection (UTI ormeningitis)

• Child abuse • Appendicitis

• Munchausen syndromeby proxy

• Gallstone

• Pancreatitis• Bulimia• IBD

IBD¼inflammatory bowel disease; GER¼gastroesophageal reflux; GERD¼gastroesophageal reflux disease; UTI¼urinary tract infection.



development of pyloric stenosis. (5) Ten cases associatingthe use of azithromycin with pyloric stenosis have beenreported. (6) Maternal use of macrolide antibiotics duringlate pregnancy and during breastfeeding have also beenlinked to the development of pyloric stenosis. The typicalpresentation is a 3- to 6-week-old infant with progressiveor intermittent vomiting after feeding. The vomiting is of-ten projectile in nature, and 1.4% of patients present withbilious emesis. The infant is hungry after vomiting. Infantswith continued vomiting develop hypochloremic, hypoka-lemic contraction alkalosis and aciduria. On physical exam-ination an olivelike mass is appreciated in the rightmidepigastrium,mostly after emesis. Visible gastric peristal-sis is seen with feeding. Icteropyloric syndrome is a combi-nation of hyperbilirubinemia and pyloric stenosis seen in upto 8% of infants. The hyperbilirubinemia is usually indirectand thought to be secondary to increased enterohepaticcirculation and decreased glucuronyl transferase activity.The diagnosis of pyloric stenosis is usually made by ab-dominal ultrasonography. Ultrasonographic diagnosticcriteria consist of pyloric thickness of 3 to 4 mm, pyloriclength of 15 to 19 mm, and pyloric diameter of 10to 14mm (Fig 2). (7) A barium study of the upper GI tractcan also be used to make the diagnosis and has theadded advantage of excluding other obstructive lesions,such as antral web or malrotation with volvulus, al-though it carries considerable radiation exposure andexpense. The typical features of pyloric stenosis on a bar-ium study of the upper GI tract are elongated pyloriccanal (string sign), a bulge of the pyloric muscle intothe antrum (shoulder sign), narrowed ending of pyloriccanal (beak sign), and parallel streaks of barium seen inthe narrowed channel (double tract sign).

Once the diagnosis is made, the goal is to correct thefluid, electrolyte, and acid-base imbalance before pro-ceeding to surgery. There is a risk of postoperative ap-nea if alkalosis is not corrected before the surgery. Thesurgery performed is pyloromyotomy in which the py-lorus is split longitudinally down to the submucosa torelieve the stenosis. Several randomized controlledstudies have reported that there is no significant differ-ence between open vs laparoscopic pyloromyotomy, ex-cept for cosmetic reasons and center availability oflaparoscopy. (8)

Intestinal AtresiaThe small intestine is the most common site of intestinalatresia, with an occurrence of 2.8 per 10, 000 live births.Duodenal atresia contributes 49%, followed by jejunalatresia at 36% and ileal atresia at 14%. Intestinal atresiais thought to result from a lack of revacuolization ofthe intestinal solid cord stage and a late intrauterine mes-enteric vascular incident along with genetic factors. Jeju-noileal atresia may be seen in normal full-term infants;however, it is usually associated with congenital anoma-lies, such as gastroschisis, internal hernia, and volvulus.Fifty percent of duodenal atresia cases are seen in prema-ture infants. Duodenal atresia is seen in 25% to 50% ofinfants with Down syndrome. Other associated congen-ital anomalies include congenital heart disease, annularpancreas, malrotation, renal anomalies, skeletal malfor-mations, and esophageal atresia. (9) Infants present withbilious vomiting, abdominal distension, and failure topass meconium. There is a history of maternal polyhy-dramnios, and one-third of patients have jaundice. Ab-dominal radiographs show the pathognomonic “double

Figure 2. Abdominal ultrasonogram showing elongatedpyloric muscle suggestive of pyloric stenosis.

Figure 3. Plain abdomen radiograph showing double bubblesign suggestive of duodenal atresia.



bubble sign” (Fig 3). Additional imaging studies (eg,echo, renal ultrasonography, and vertebral radiograph)should be performed to exclude associated malforma-tions. Initial management includes bowel rest along withnasogastric or orogastric decompression. Correctionof dehydration and electrolyte abnormalities should bepromptly undertaken. Once the patient is hemodynami-cally stable, surgical intervention is essential.

Congenital anomalies that cause bowel obstruction(eg, duodenal web, malrotation, and annular pancreas)usually present during infancy; however, they may pres-ent later in life if the obstruction is partial.

Causes of Vomiting Beyond InfancyAcute Gastroenteritis

Although it may occur in infants, acute gastroenteritis isthe most common reason for vomiting beyond infancy.Viruses are the most common cause of gastroenteritis fol-lowed by bacteria and parasites. The typical presentationis acute onset of vomiting followed by diarrhea. Vomitingis a self-protective process that may reduce the load of theinfectious organisms and associated toxins or irritants thatcause the vomiting. The use of antiemetics in acute gas-troenteritis has been controversial. Recent meta-analysesof reported studies, however, suggest that ondansetronreduces vomiting and the need forhospitalization or intravenous flu-ids in children with acute gastro-enteritis. However, ondansetronalso may increase diarrhea in suchpatients. Rehydration (oral, en-teral, or intravenous) is key to su-ccessful management of acutegastroenteritis.

Eosinophilic EsophagitisSevere EE previously was thoughtto be due to severe GERD, but pa-tients with this condition failed torespond to medical managementof GERD. Now this condition isconsidered a different disease entity.The etiopathogenesis of EE remainsunknown, although it is postulatedthat in some patients infiltrationwith eosinophils may be related tofood allergen hypersensitivity. Inmany patients, however, no specificfood allergen is identified. Otheretiologic possibilities mentioned in

the literature include reaction to aeroallergens, particu-larly because in some patients EE is seasonal, and to T-cell–mediated immune dysregulation. The incidence ofEE is 1.2 per 10,000 children. (10) The prevalence ofEE in population-based studies is 4.2 per 10,000 children,but the literature shows that the prevalence is increasing.The male-female ratio is 3:1. The mean age of diagnosis is8.6 years. The presenting symptoms vary based on theage at presentation; feeding dysfunction is seen in thetoddler age group (1-4 years old), vomiting in the childage group (4-12 years old), abdominal pain in the 10- to15-year-old age group, dysphagia in the 10- to 17-year-old age group, and food impaction in the 14- to 20-year-old age group. Other symptoms include failure to thriveand chest pain. Often EE is seen in patients with otherallergic diseases, such as asthma, eczema, food allergy, al-lergic rhinitis, and urticaria.

Endoscopy of the upper GI tract with biopsy is re-quired to make the diagnosis of EE. The endoscopic fea-tures suggestive of EE include linear furrowing or verticallines, white exudates, circular rings or trachealization,and strictures of the esophagus (Fig 4). The histologicfeatures of EE include increased number of eosinophils(‡15 intraepithelial eosinophils per high-power fieldof the microscope) at multiple levels of the

Figure 4. Endoscopic images of esophagus showing normal mucosa (a), vertical line (b),white specks (c), and) rings (trachealization) (d).



esophagus, eosinophilic microabscesses, and basalcell hyperplasia. (11)

Treatment options for EE include acid suppression,corticosteroids (topical and systemic), and dietary modi-fications. Esophageal eosinophilia that responds to PPIs iscalled PPI-responsive EE and is considered a separate en-tity from EE. It is hypothesized that the mechanisms bywhich a PPI may improve the symptoms of EE includetreatment of coexisting GERD and/or a direct anti-in-flammatory effect of the PPI. Swallowed fluticasonegiven usually as 2 puffs swallowed 2 times a day has beeneffective in treating EE. The dose varies, based on pa-tient age, from 44 to 220 mg per swallowed puff. Re-sponse is appreciated by patients within a week;however, symptom relapse once the treatment is discon-tinued is common. Indications for maintenance therapy arenot well established. Dietary modification treatment op-tions include an elimination diet based on allergy testing,an empiric elimination diet (milk, soy, egg, peanut, wheat,and fish), or a complete elemental diet (amino acid for-mula). (11) Cautious esophageal dilation is helpful in pa-tients with esophageal stricture causing dysphagia andrecurrent food impaction. The prognosis of EE is unknown.

Rumination SyndromeRumination is defined as effortless regurgitation of re-cently ingested food into the mouth with subsequentmastication and reswallowing or expulsion. Ruminationis seen in 3 distinct populations: infants, persons witha psychiatric disorder, and healthy adolescents or adults.

The incidence and prevalence of rumination syndromeare unknown, but recent literature suggests that it is oc-curring more frequently. It is more common in adoles-cent and older females than males. Weight loss (42%)is commonly seen in adolescents at the onset of rumina-tion syndrome. Other associated symptoms include ab-dominal pain (38%), constipation (21%), nausea (17%),and diarrhea (8%). (12) Rumination syndrome also affectsthe quality of life of the patient, including absenteeismfrom school or work (72%) and frequent hospitalizations.The exact cause is unknown, but in some patients the on-set of symptoms coincides with the occurrence of a stressfulevent. In the literature, an association with eating disorders(20%) has been reported.

The hypothesized pathophysiologic finding in rumi-nation syndrome is repeated voluntary abdominal musclewall contraction, causing increased gastric pressureand resulting in movement of gastric content to theesophagus and out.

The diagnosis of rumination is usually made by his-tory as described in the Rome III criteria for diagnosis

of functional GI disorders and must include all of thefollowing:

1. Repeated painless regurgitation and rechewing or ex-pulsion of food that:

a. Begins soon after ingestion of a mealb. Does not occur during sleepc. Does not respond to standard treatment for GER

2. Absence of retching3. Absence of evidence of an inflammatory, anatomical,

metabolic, or neoplastic process that explains the pa-tient’s symptoms.

These criteria should have been present for the last 3months, and the onset of symptoms should have been atleast 6 months before diagnosis.

Physicians’ lack of familiarity can result in missed diag-nosis of rumination syndrome. These patients are oftenmisdiagnosed as having GERD, dyspepsia, or gastroparesis.

Additional diagnostic testing can be considered ifthere is diagnostic ambiguity or if the patient or familyfails to accept the diagnosis. This may include an esoph-ageal pH study that reveals rapid fluctuation in luminalpH secondary to repeated regurgitation and reswallow-ing within the first 1 to 2 hours after eating but not duringsleep and/or antroduodenal manometry that reveals the pa-thognomonic synchronous increase in pressure (R wave)across multiple recording sites (Fig 5). The R wave repre-sents increased intra-abdominal pressure from voluntary ab-dominal wall muscle contraction. Fasting manometryresults are otherwise normal. Endoscopy has no role in di-agnosis but rules out other causes, such as GER and EE.The differential diagnosis for rumination syndrome includesGERD, gastroparesis, and achalasia.

MANAGEMENT OF RUMINATION SYNDROME. Themost effective treatment option is behavioral therapy(85% success rate). Diaphragmatic breathing acts asa habit reversal technique by teaching the patient relaxa-tion of the diaphragm instead of contraction, which thenprevents regurgitation. (12)

Initiation of a multidisciplinary approach by involvingthe patient, parents, primary care physicians, and behavioraltherapist at the earliest is key to successful management.

If the patient has had a significant amount of weightloss transpyloric enteral nutritional support may be con-sidered. If there is evidence of esophagitis, a PPI shouldbe prescribed. Other treatment options, such as chewinggum, use of a prokinetic agent, baclofen, antidepressants,and antireflux surgery, have been offered, but there is noevidence that these treatment options are effective.



Cyclic Vomiting SyndromeCVS is a functional disorder characterized by stereotyp-ical episodes of nausea and vomiting lasting for hours todays, with the patient being asymptomatic and healthybetween the episodes of vomiting. The exact incidenceand prevalence are unknown. The estimated prevalenceis between 1.9% and 2.3%. (13) CVS starts during thepreschool years in most patients, but it is usually diag-nosed around 9 years of age. The male-female ratio is 4:6.

CVS is strongly associated with migraine headaches;80% of patients with CVS have a family history of mi-graine headaches, and 80% of patients with CVS respondto antimigraine treatment. Most patients with CVS willoutgrow it by the teenage years; however, approximately75% will develop migraine headaches by adulthood.Some patients with CVS develop abdominal migrainesbefore developing migraine headaches. The origin of

CVS is idiopathic in 90% of patients. Various mitochon-drial disorders have been strongly linked to CVS. Mito-chondrial DNA polymorphisms, specifically 1651T and3010A, have been reported to be associated with CVS.Other associated conditions include hereditary sensoryautonomic neuropathy, cannabis hyperemesis syndrome,metabolic and endocrine disorders. Patients with CVS typ-ically have acute onset of nausea and vomiting beginningin the early morning hours. Other associated symptoms in-clude pallor, photophobia, lethargy, anorexia, headache,diarrhea, visual changes, and abdominal pain. Each episodelasts for a few hours to a few days followed by symptom-free intervals, which, like associated symptoms such as thetime of onset of vomiting, the pattern of vomiting, and du-ration of vomiting, is stereotypical for the individual but isat least 1 week long. Common triggers are infection andemotional changes. The emotional stress may be positive

Figure 5. Antroduodenal manometry showing an R wave suggestive of rumination syndrome.



(eg, birthday event) or negative (eg, school examination).Two additional distinct CVS syndromes have been de-scribed in the literature:

CVS plus indicates the presence of neurologic features(eg, seizure, developmental delay, hypotonia) in additionto CVS symptoms. Patients with CVS plus present at anearlier age and have increased occurrence of migraineheadaches and pain syndrome. Catamenial CVS is thepresence of CVS symptoms at the onset of the menstrualcycle.

The Rome III diagnostic criteria for CVS include all ofthe following:

1. Stereotypical episodes of vomiting regarding onset(acute) and duration (<1 week)

2. Three or more discrete episodes in the prior year3. Absence of nausea and vomiting between episodes

These criteria should have been fulfilled within the last3 months, and the symptom onset should have been atleast 6 months before diagnosis.

A supportive criterion is the presence of a history orfamily history of migraine headaches.

Initial evaluation should include an upper GI tract se-ries to exclude malrotation and a basic metabolic profileto exclude electrolyte abnormalities and hypoglycemia.Additional evaluation depends on the presence of otherrisk factors or alarm symptoms. If the patient has local-ized abdominal pain, abdominal ultrasonography and se-rum amylase and lipase measurement may be warranted.Patients with hematemesis require endoscopy.

If the symptoms are triggered by fasting, a high pro-tein diet, or an intercurrent illness, the patient requiresa metabolic workup, including blood glucose, ammonia,

lactate, pyruvate, urine ketone, serum AA, acylcarnitineprofile, and urine organic acid, to rule out metabolicdisorders.

Patients in the CVS plus subcategory warrant serumamino acid and urine organic acid testing.

Patients with neurologic signs and symptoms and pro-gressive vomiting should undergo brain magnetic reso-nance imaging to evaluate for an intracranial process.(Fig 6)

Cannabis overuse can result in cannabis hyperemesissyndrome, which is similar to CVS. These patients needto abstain from using cannabis for 2 weeks before any ad-ditional workup is initiated.

TreatmentLifestyle modification is important in preventing episodesof CVS and includes sleep hygiene and avoidance of trig-gers, such as fasting, caffeine, and chocolate. Educatingthe patient and family about CVS is helpful. Any under-lying disease should be treated. (13)

The treatment of CVS includes treatment of an acuteepisode followed by prophylactic therapy. Prophylactictherapy is used if symptoms are frequent (>1 everyother month), if the patient requires hospitalization,or if the vomiting is affecting the patient’s quality of life.Tricyclic antidepressants are effective in 68% of pediatricpatients with CVS. The North American Society for Pe-diatric Gastroenterology, Hepatology and Nutritionguidelines recommend cyproheptadine for childrenyounger than 5 years and amitriptyline for childrenolder than 5 years. A combination of amitriptylineand L-carnitine was effective in 73% of patients withCVS. Amitriptyline takes a few months to be effective,which should be made clear to the patient and family.Electrocardiography before the initiation of amitrip-tyline treatment is warranted to evaluate for cardiacarrhythmias, specifically, prolonged QTc interval. Re-cent evidence also supports the use of propranolol asfirst-line prophylactic therapy; 87% of patients treatedwith propranolol had improvement in CVS symptoms.Other drugs used include phenobarbital, topiramate,and sumatriptan, which are used in migraine therapy.Birth control pills are used in females with catamenialCVS symptoms.

During acute episodes, hydration with, with appropri-ate electrolytes should be used to prevent dehydration.Hydration is also effective in decreasing the duration ofthe acute illness. Ondansetron provides symptomatic re-lief. Sedation is usually beneficial for the patient and con-trols the vomiting. Diphenhydramine, lorazepam, andchlorpromazine have been used successfully to sedate

Figure 6. Magnetic resonance image of the head showinga well-circumscribed, enhancing suprasellar mass.



patients during an acute episode of cyclic vomiting. If as-sociated abdominal pain is bothersome, ketorolac may beused to relieve the pain.

Acute Intestinal Obstruction After infancyToddlers and older children can present with acute-onsetintestinal obstruction. The typical patient presents withabdominal pain, nausea, vomiting (often bilious), ab-dominal distension, and signs of peritonitis if the obstruc-tion has been present for a prolonged period. Biliousvomiting is characteristic of intestinal obstruction distalto the ampulla of Vater. The differential diagnosis is ex-tensive and includes the following:

1. Intussusception (Fig 7)2. Malrotation with or without midgut volvulus (Fig 8)3. Incarcerated hernias4. Strictures (eg, Crohn disease [Fig 9], nonsteroidal

anti-inflammatory drugs, and irradiation)5. Adhesions6. Bezoars (Fig 10)7. Superior mesenteric artery syndrome (Fig 11)8. Small intestinal tumors (eg, carcinoid and lymphoma)

Initial EvaluationOnce intestinal obstruction is strongly suspected, gastricdecompression via a nasogastric tube should be initiatedto prevent further episodes of emesis and minimize therisk of aspiration. On the basis of the degree of obstruc-tion, the nasogastric tube can be placed to gravity or low

intermittent suction; bowel rest is key in the managementof intestinal obstruction. The degree of dehydrationshould be determined based on vital signs, physical exam-ination findings, and urinalysis results. Electrolyte

Figure 7. Abdominal ultrasonogram showing small bowel tosmall bowel intussusception in a patient with Peutz-Jegherssyndrome. Target sign is the layers of the small intestinewithin the small intestine.

Figure 8. Barium study of the upper gastrointestinal tractshowing failure of duodenal C loop to cross the vertebralcolumn and corkscrewing of third part of duodenumsuggestive of small bowel malrotation with volvulus.

Figure 9. Magnetic resonance image of the abdomen showingstricture of the bowel with prestricture and poststricturebowel dilation in a patient with Crohn disease.



abnormalities are commonly encountered and should bemanaged appropriately. Symptomatic control of nausea,vomiting, and pain should be undertaken.

Once the patient is hemodynamically stabilized, ap-propriate radiologic studies should be performed to con-firm and determine the site of obstruction. A plainradiograph of the abdomen may show air fluid levels sug-gestive of an ileus; it may also help to exclude

a perforation as a complication of prolonged obstruction.A barium study of the upper GI tract is most helpful inthe evaluation for small bowel obstruction. A barium en-ema may be necessary if the obstruction is in the lower GItract. Pediatric surgery consultation is mandated when in-testinal obstruction is suspected.

Antiemetic MedicationsAntiemetics are categorized into 6 groups based on thereceptor of action. Serotonin receptor antagonists arethe most commonly used antiemetics in clinical practice.Drugs in this category include ondansetron, granisetron,dolasetron, and palonosetron. These drugs act on seroto-nin receptors located at the solitary tract nucleus, vagalafferents, and the chemoreceptor trigger zone to suppressnausea and vomiting. Common indications for this groupof medications are chemotherapy-induced nausea andvomiting and postoperative and postirradiation nauseaand vomiting. These drugs are well tolerated. Commonadverse effects include headache, asthenia, constipationand dizziness.

Dopamine receptor antagonists include pheno-thiazines (prochlorperazine and chlorpromazine),butyrophenones (droperidol and haloperidol), andbenzamides (metoclopramide and domperidone). Pheno-thiazines are commonly used as antiemetics. They act onD2-receptors at the chemoreceptor trigger zone. They alsohave antihistaminic (H1) and anticholinergic (M1) ef-fects. Common adverse effects are extrapyramidal reac-tions, which can be treated with diphenhydramine, anddrowsiness

Metoclopramide has peripheral antidopamine (D2) ef-fects in addition to central antidopamine effects. It alsostimulates cholinergic receptors, resulting in gastric peri-stalsis. It has a black box warning from the US Food andDrug Administration because of tardive dyskinesia withlong-term use. It is commonly used to treat gastroparesis.

Domperidone has a selective peripheral antidopamine(D2) effect in the upper GI tract. It does not cross theblood brain barrier and so does not have the central ner-vous system adverse effects seen with metoclopramide.This drug, however, is not available in the United States.

H1-receptor antagonists include cyclizine, hydroxy-zine, promethazine, and diphenhydramine. These drugsare commonly used as antiemetic agents. A common ad-verse effect is sedation.

The muscarinic receptor antagonist scopolamine acts onM1 receptors. It is used as a prophylactic medication to pre-vent motion sickness. It is supplied as a transdermal patch.

Neurokinin receptor antagonists are a new class ofantiemetic drugs that block the substance P–mediated

Figure 10. Computed tomograph of the abdomen showingheterogeneous mass in the stomach with mottled air patternand oral contrast material surrounding the mass in a patientwith gastric bezoar.

Figure 11. Barium study of the upper gastrointestinal tractshowing dilation of the first and second portions of theduodenum with abrupt narrowing of the third position ofthe duodenum suggestive of superior mesenteric arterysyndrome.



nausea and vomiting via neurokinin receptors. Drugs inthis category include aprepitant (oral formulation) andfosaprepitant (parenteral formulation). These medica-tions are primarily used for prevention and treatmentof chemotherapy-induced nausea and vomiting. Com-pared with serotonin receptor antagonists, these drugsprevent delayed emesis associated with strongly emeto-genic chemotherapy agents, such as cisplatin. An optimalresult is achieved if used in conjunction with a serotoninreceptor antagonist and dexamethasone.

The cannabinoid receptor agonist dronabinol is usedto treat chemotherapy-induced nausea and vomitingwhen other antiemetics are not effective.

References1. Quigley EMM, Hasler WL, Parkman HP. AGA technical reviewon nausea and vomiting. Gastroenterology. 2001;120(1):263–2862. Nelson SP, Chen EH, Syniar GM, Christoffel KK; PediatricPractice Research Group. Prevalence of symptoms of gastroesoph-ageal reflux during infancy: pediatric practice-based survey. ArchPediatr Adolesc Med. 1997;151(6):569–5723. Vandenplas Y, Rudolph CD, Di Lorenzo C, et al; NorthAmerican Society for Pediatric Gastroenterology Hepatology andNutrition; European Society for Pediatric Gastroenterology Hep-

atology and Nutrition. Pediatric gastroesophageal reflux clinicalpractice guidelines: joint recommendations of the North AmericanSociety for Pediatric Gastroenterology, Hepatology, and Nutrition(NASPGHAN) and the European Society for Pediatric Gastroen-terology, Hepatology, and Nutrition (ESPGHAN). J PediatrGastroenterol Nutr. 2009;49(4):498–5474. Horvath A, Dziechciarz P, Szajewska H. The effect of thickened-feed interventions on gastroesophageal reflux in infants: systematicreview and meta-analysis of randomized, controlled trials. Pediat-rics. 2008;122(6):e1268–e12775. Honein MA, Paulozzi LJ, Himelright IM, et al. Infantilehypertrophic pyloric stenosis after pertussis prophylaxis with eryth-romycin: a case review and cohort study. Lancet. 1999;354(9196):2101–21056. Azithromycin and pyloric stenosis. http://www.drugcite.com/indi/?q=Azithromycin&i=PYLORIC%20STENOSIS. Accessed September 12,2012.7. Rohrschneider WK, Mittnacht H, Darge K, Tröger J. Pyloricmuscle in asymptomatic infants: sonographic evaluation anddiscrimination from idiopathic hypertrophic pyloric stenosis. Pe-diatr Radiol. 1998;28(6):429–4348. Perger L, Fuchs JR, Komidar L, Mooney DP. Impact of surgicalapproach on outcome in 622 consecutive pyloromyotomies ata pediatric teaching institution. J Pediatr Surg. 2009;44(11):2119–21259. Tulloh RM, Tansey SP, Parashar K, De Giovanni JV, Wright JG,Silove ED. Echocardiographic screening in neonates undergoingsurgery for selected gastrointestinal malformations. Arch Dis ChildFetal Neonatal Ed. 1994;70(3):F206–F20810. Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esoph-agitis. N Engl J Med. 2004;351(9):940–94111. Furuta GT, Liacouras CA, Collins MH, et al; First In-ternational Gastrointestinal Eosinophil Research Symposium(FIGERS) Subcommittees. Eosinophilic esophagitis in childrenand adults: a systematic review and consensus recommendationsfor diagnosis and treatment. Gastroenterology. 2007;133(4):1342–136312. Chial HJ, Camilleri M, Williams DE, Litzinger K, Perrault J.Rumination syndrome in children and adolescents: diagnosis,treatment, and prognosis. Pediatrics. 2003;111(1):158–16213. Li BU, Lefevre F, Chelimsky GG, et al; North AmericanSociety for Pediatric Gastroenterology, Hepatology, and Nutrition.North American Society for Pediatric Gastroenterology, Hepatol-ogy, and Nutrition consensus statement on the diagnosis andmanagement of cyclic vomiting syndrome. J Pediatr GastroenterolNutr. 2008;47(3):379–393

Summary

• Vomiting can be the presenting symptom of a varietyof disorders, ranging from self-limited diseases tolife-threatening diseases.

• The causes of vomiting vary with age of presentation,and pediatricians should develop the skill to identifyserious conditions at the earliest stage based on theage of presentation.

• Bilious emesis at any age is a sign of intestinalobstruction until proven otherwise and needsimmediate attention.

• Vomiting is not always due to a GI disorder, andpediatricians should look for causes outside the GItract if no GI disease is identified.

Parent Resources from the AAP at HealthyChildren.org

The reader is likely to find material relevant to this article to share with parents by visiting these links:

• http://www.healthychildren.org/English/health-issues/conditions/abdominal/Pages/Treating-Vomiting.aspx• http://www.healthychildren.org/English/health-issues/conditions/abdominal/Pages/Infant-Vomiting.aspx• http://www.healthychildren.org/English/health-issues/conditions/abdominal/Pages/Drinks-to-Prevent-Dehydration-in-

a-Vomiting-Child.aspx



http://www.drugcite.com/indi/?q=Azithromycin&i=PYLORIC%20STENOSIS

http://www.drugcite.com/indi/?q=Azithromycin&i=PYLORIC%20STENOSIS

PIR QuizThis quiz is available online at http://www.pedsinreview.aappublications.org. NOTE: Learners can take Pediatrics in Review quizzes and claim creditonline only. No paper answer form will be printed in the journal.

New Minimum Performance Level RequirementsPer the 2010 revision of the American Medical Association (AMA) Physician’s Recognition Award (PRA) and credit system, a minimum performancelevel must be established on enduring material and journal-based CME activities that are certified for AMA PRA Category 1 CreditTM. In order tosuccessfully complete 2013 Pediatrics in Review articles for AMA PRA Category 1 CreditTM, learners must demonstrate a minimum performancelevel of 60% or higher on this assessment, which measures achievement of the educational purpose and/or objectives of this activity.

In Pediatrics in Review, AMA PRA Category 1 CreditTM may be claimed only if 60% or more of the questions are answered correctly. If you score lessthan 60% on the assessment, you will be given additional opportunities to answer questions until an overall 60% or greater score is achieved.

1. A 3-month-old boy is seen by his pediatrician because of frequent vomiting. His parents report that since birthhe spit up small amounts of formula after each feed but, over time, the amount regurgitated during eachepisode increased. Currently, regurgitation follows every feeding; it is non-projectile and non-bilious. Theinfant is otherwise healthy and developing normally; length and weight are each in the 75% for age. What isthe most appropriate first step in management?

A. Initiate a trial of once daily proton pump inhibitor therapy.B. Institute a 2-4 week trial of a hypoallergenic formula.C. Reassure parents that regurgitation is likely to gradually resolve.D. Schedule an esophageal endoscopy study with biopsy.E. Schedule an esophageal pH monitoring study.

2. A 34-week premature male developed bilious vomiting and abdominal distention within hours after birth.Prenatal course was complicated by maternal polyhydramnios and a sinus infection. A small amount ofmeconium was passed in the delivery room but since that time no further meconium stools were passed.Abdominal radiographs reveal a “double bubble sign.” Physical examination and additional imaging studiesreveal no other abnormalities or malformations. Stabilization of fluid and electrolytes are conducted as thepatient is prepared for surgery. Which of the following is the most likely diagnosis?

A. Duodenal atresia.B. Duodenal web.C. Ileal atresia.D. Jejunal atresia.E. Malrotation.

3. A previously healthy 4-year-old girl presents with a history of intermittent vomiting occurring 10-12 times inthe previous eight months. During each bout the child vomits 8-10 times during a 24-48 hour period. Eachepisode begins early in the day with nausea followed by repeated vomiting and is accompanied by dizziness,anorexia and mild abdominal pain. Several of the episodes have been accompanied by an upper respiratoryinfection or acute otitis media. Between episodes, the child has felt well, with no complaints. She is doing wellin pre-kindergarten. Her mother and maternal grandmother have migraine headaches. History is otherwiseunrevealing and physical examination, including growth parameters and vital signs and neurologic exam, isnormal. A basic metabolic profile and upper GI series were normal. In addition to lifestyle modification, such assleep hygiene, which of the following is the most appropriate next step in management for this child?

A. Amitriptyline.B. Cyproheptadine.C. Diphenhydramine.D. Ketorolac.E. Phenobarbital.



4. A previously healthy 2-year-old girl developed nonbilious vomiting and fever to 103.5 F (39.72C). She wasfussy and somewhat difficult to console. She had one loose stool but continued to vomit and remained febrilefor 72 hours. On physical examination, she appears mildly dehydrated, with a soft, nontender abdomen. Exceptfor a 5% weight loss, the rest of her physical examination is normal. Which of the following etiologies shouldbe pursued as the most likely cause of this child’s symptoms?

A. Acute gastroenteritis.B. Esophagitis.C. Intestinal malrotation.D. Pharyngitis.E. Urinary tract infection.

5. A 12-year-old male has migraines and motion sickness. Which of the following medications is mostappropriate to prescribe for the prevention of motion sickness?

A. Aprepitant.B. Chlorpromazine.C. Hydroxyzine.D. Ondansetron.E. Scopalamine.

Poetic License

Vomiting causes surprises!No choices when the gorge rises.Before writing prescriptions,Get careful descriptions –Symptoms are often disguises.

–MCM



Documents

Vomiting may suggest mucosal disease of the gastrointestinal tract, such as inﬂammatory bowel disease Fever: if persistent (>72 hours), if child appears ill, or if in an infant younger