Gastroesophageal Reflux in Children

Definitions

Passage of gastric contents into esophagus Passage of gastric contents into esophagus is called GERis called GER

Definitions

GER Passage of gastric contents into esophagus

Regurgitation / Spitting-up

Passage of refluxed gastric content into oral Pharynx & mouth Drooling

Vomiting Expulsion of refluxed gastric

contents from mouth

GERD Gastric contents reflux into the

Esophagus/oropharynx &

produce symptoms/complications

Rumination Voluntary, habitual regurgitation of recently ingested food that is subsequently spitted up or re-swallowed

Definitions

Pathogenic Factors in GER

Mechanisms of GER:Mechanisms of GER:

TLESR: transient TLESR: transient lower esophageal lower esophageal sphincter relaxationsphincter relaxation

Delayed gastric Delayed gastric emptyingemptying

Impaired esophageal Impaired esophageal clearanceclearance

Impaired airway Impaired airway protectionprotection

Pathogenic Factors in GER

TLESR:TLESR:Primary mechanismPrimary mechanism for reflux to occur for reflux to occurTLESRs occur independent of swallowing, reducing LES TLESRs occur independent of swallowing, reducing LES pressure to 0–2 mm Hg (above gastric), and last >10 sec; pressure to 0–2 mm Hg (above gastric), and last >10 sec; they appear by 26 wk of gestationthey appear by 26 wk of gestationA A vagovagal reflexvagovagal reflex, composed of afferent , composed of afferent mechanoreceptors in the proximal stomach, a brainstem mechanoreceptors in the proximal stomach, a brainstem pattern generator, and efferents in the LES, regulates pattern generator, and efferents in the LES, regulates TLESRsTLESRsGastric distentionGastric distention (postprandially, or due to abnormal (postprandially, or due to abnormal gastric emptying or air swallowing) is the gastric emptying or air swallowing) is the main stimulusmain stimulus for TLESRsfor TLESRs

Pathogenic Factors in GER

TLESR:TLESR:Whether GERD is caused by a higher frequency of Whether GERD is caused by a higher frequency of TLESRs or by a greater incidence of reflux during TLESRs or by a greater incidence of reflux during TLESRs is debated; each is likely in different individuals. TLESRs is debated; each is likely in different individuals. Straining during a TLESR makes reflux more likely, as do Straining during a TLESR makes reflux more likely, as do positions that place the gastroesophageal junction below positions that place the gastroesophageal junction below the air-fluid interface in the stomachthe air-fluid interface in the stomachOther factors influencing gastric pressure-volume Other factors influencing gastric pressure-volume dynamics, such as increased movement, dynamics, such as increased movement, strainingstraining, , obesityobesity, , large-volume or hyperosmolar mealslarge-volume or hyperosmolar meals, and , and increased respiratory effort (coughing, wheezing) can increased respiratory effort (coughing, wheezing) can have the same effecthave the same effect

PrevalencePrevalence

GER is a GER is a physiologicalphysiological phenomenon, occurring in every phenomenon, occurring in every individual. Most episodes of reflux are limited to the individual. Most episodes of reflux are limited to the distal esophagus, and are distal esophagus, and are brief and asymptomaticbrief and asymptomatic..

Sometimes GER is a normal esophageal function, Sometimes GER is a normal esophageal function, serving a protective role, e.g. during meals, or in the serving a protective role, e.g. during meals, or in the immediate postprandial period; if the stomach is immediate postprandial period; if the stomach is overdistended, GER serves to decompress it.overdistended, GER serves to decompress it.

Regurgitation may be physiologicalRegurgitation may be physiological in healthy, thriving, in healthy, thriving, happy infants. happy infants. Primary GERPrimary GER results from a primary results from a primary disorder of function of the upper GI tractdisorder of function of the upper GI tract

In In secondary GERsecondary GER, reflux results from dysmotility , reflux results from dysmotility occurring in occurring in systemic disorderssystemic disorders such as neurological such as neurological impairment or systemic sclerosisimpairment or systemic sclerosis

PrevalencePrevalence

It may also result from It may also result from mechanical factorsmechanical factors at play in at play in chronic lung disease or upper airway obstruction, as in chronic lung disease or upper airway obstruction, as in chronic tonsillitis. Other causes include chronic tonsillitis. Other causes include systemic or systemic or local infectionslocal infections (urinary tract infection, gastroenteritis), (urinary tract infection, gastroenteritis), food allergy, metabolic disorders, intracranial food allergy, metabolic disorders, intracranial hypertension and medications such as chemotherapy. hypertension and medications such as chemotherapy. In some cases, In some cases, secondary refluxsecondary reflux results results from from stimulation of the vomiting centerstimulation of the vomiting center by afferent impulses by afferent impulses from circulating bacterial toxins, or stimulation from from circulating bacterial toxins, or stimulation from sites such as the eye, olfactory epithelium, labyrinths, sites such as the eye, olfactory epithelium, labyrinths, pharynx, gastrointestinal and urinary tracts, and testes. pharynx, gastrointestinal and urinary tracts, and testes. These stimuli usually cause vomiting.These stimuli usually cause vomiting.

Textbook of Pediatric Gastroenterology and Nutrition, Stefano Guandalini, 1Textbook of Pediatric Gastroenterology and Nutrition, Stefano Guandalini, 1 stst Ed, 2004 Ed, 2004

A small degree of reflux is A small degree of reflux is common in all common in all infantsinfants, and it is only infants who have moderate , and it is only infants who have moderate to severe chronic reflux that tend to come to the to severe chronic reflux that tend to come to the pediatrician's attentionpediatrician's attentionOne of the most common causes of GER is One of the most common causes of GER is overfeeding, so a careful history is importantoverfeeding, so a careful history is importantA history of coughing, gagging, and arching of A history of coughing, gagging, and arching of the back with extensor posturing the back with extensor posturing during feedingduring feeding may result from direct may result from direct aspirationaspiration, whereas the , whereas the presence of these presence of these symptomssymptoms soon soon after feedingafter feeding may may suggest GERsuggest GERIn severe reflux, the infant may have poor In severe reflux, the infant may have poor weight gainweight gain

PrevalencePrevalence

Definitions

Prevalence of Regurgitation: Prevalence of Regurgitation: InfantsInfants

Recurrent vomitingRecurrent vomiting occurs in 50% of infants in the first three occurs in 50% of infants in the first three months of life, in 67% of months of life, in 67% of four monthfour month old infants, & in 5% of 10 to old infants, & in 5% of 10 to 12 month old infants. Vomiting resolves spontaneously in nearly 12 month old infants. Vomiting resolves spontaneously in nearly all by 24 months!all by 24 months!

Prevalence of Regurgitation: Prevalence of Regurgitation: InfantsInfants

Determination of the exact prevalence of GER & GERD at Determination of the exact prevalence of GER & GERD at any age is virtually impossible because any age is virtually impossible because mostmost reflux reflux episodes are episodes are asymptomaticasymptomatic, show the absence of specific , show the absence of specific symptoms, undergo self-treatment and lack medical symptoms, undergo self-treatment and lack medical referral.referral.

Prevalence of GERD in children is not well defined, but Prevalence of GERD in children is not well defined, but community based studies suggest that symptoms may be community based studies suggest that symptoms may be present in present in 1.8 to 22%1.8 to 22% of children aged 3 to 18 years. of children aged 3 to 18 years. 11

A prevalence of A prevalence of 10%10% was found was found among Indianamong Indian children in children in the age group of 1month to 2 years.the age group of 1month to 2 years.22

1. J Pediatr 2005; 146 : S3 – S121. J Pediatr 2005; 146 : S3 – S12

2.Trop Gastroenterol 2001;22:99-1022.Trop Gastroenterol 2001;22:99-102

EtiologyEtiology

Genetic predispositionGenetic predisposition Environmental factors Environmental factors

Food habit Food habit Eating fastEating fast Obesity Obesity Stress Stress Exposure to tobacco Exposure to tobacco

smokesmoke Neurologically impaired Neurologically impaired

children, Repaired children, Repaired esophageal atresia, BPD, esophageal atresia, BPD, cystic fibrosis, ?H. pyloricystic fibrosis, ?H. pylori

EtiologyEtiology

Factors affecting GERFactors affecting GER

Spectrum of ManifestationsSpectrum of Manifestations

Sign & Symptoms

InfantsInfants Older Children & Older Children & AdolescentsAdolescents

Feeding resistanceFeeding resistanceRecurrent vomitingRecurrent vomitingFailure to thriveFailure to thriveFussiness/irritabilityFussiness/irritabilityApnea/choking Apnea/choking episodesepisodesOpisthotonic Opisthotonic posturingposturing

Abdominal painAbdominal painHeartburnHeartburnRecurrent vomitingRecurrent vomitingDysphagiaDysphagiaChronic Chronic cough/cough/wheezingwheezingHoarsenessHoarsenessPostnasal dripPostnasal drip

Manifestations

Manifestations

• EsophagitisEsophagitis• Peptic stricturePeptic stricture• Barrett’s esophagusBarrett’s esophagus• Failure to thriveFailure to thrive• Pulmonary / Pulmonary / ENT diseaseENT disease• Sandifer’s syndrome Sandifer’s syndrome

// torticollistorticollis

• EsophagitisEsophagitis• Peptic stricturePeptic stricture• Barrett’s esophagusBarrett’s esophagus• Failure to thriveFailure to thrive• Pulmonary / Pulmonary / ENT diseaseENT disease• Sandifer’s syndrome Sandifer’s syndrome

// torticollistorticollis

Complications

GERD & AsthmaGERD & Asthma

Asthma

GERD

50-60% of childhood asthmatic patients experience GERD50-60% of childhood asthmatic patients experience GERD

Pedatr Drugs.2005;7:177-186Pedatr Drugs.2005;7:177-186

Aspiration of refluxed Aspiration of refluxed gastric contents (micro- or gastric contents (micro- or macro-aspiration)macro-aspiration)

Vagally-mediated reflex Vagally-mediated reflex bronchospasmbronchospasm

GERD & rhinosinusitis GERD & rhinosinusitis cause chronic, intermittent cause chronic, intermittent cough. Both can be cough. Both can be comorbidities of asthmacomorbidities of asthma

Am J Med 2001; 111: 37SAm J Med 2001; 111: 37S

Does GERD Does GERD TriggerTrigger Asthma? Asthma?

Progressive and Progressive and resistant asthmaresistant asthma Symptoms of GERD presentSymptoms of GERD present ExacerbationsExacerbations during sleep and after during sleep and after

mealsmeals Symptoms Symptoms worsenworsen after bronchodilator after bronchodilator

administrationadministration

AGA Consensus Development Conference, 2002AGA Consensus Development Conference, 2002

When to When to SuspectSuspect GERD Related GERD Related AsthmaAsthma

Asthma & GERD

Asthma & GERD

GERD is diagnosed on basis of history & clinical GERD is diagnosed on basis of history & clinical featuresfeatures

No fool proof test for diagnosisNo fool proof test for diagnosis

An An empiric trial of PPI therapyempiric trial of PPI therapy is a widely used diagnostic test is a widely used diagnostic test for GERD in adults and this approach is expanding to pediatric for GERD in adults and this approach is expanding to pediatric practice nowpractice now11

oBarium meal seriesBarium meal series

oEndoscopy and biopsyEndoscopy and biopsy

oIntraesophageal pH monitoringIntraesophageal pH monitoring

1.Am J Med 2004; 117: 23S – 29S1.Am J Med 2004; 117: 23S – 29S

DiagnosisDiagnosis

Emesis shortly after feeds Emesis shortly after feeds GER GERIf the emesis is projectile & the child is 1 to 3 months old If the emesis is projectile & the child is 1 to 3 months old pyloric stenosis pyloric stenosisPoor weight gain & emesis Poor weight gain & emesis pyloric stenosis or pyloric stenosis or metabolic disordermetabolic disorderDrug Tx: Macrolide antibiotics Drug Tx: Macrolide antibiotics emesis and diarrhea, emesis and diarrhea, chemotherapeutic agents & toxic ingestions chemotherapeutic agents & toxic ingestions emesis emesisChild with VP shunt, vomiting Child with VP shunt, vomiting shunt obstruction & shunt obstruction & icpicpEmesis with seizure or headache or both Emesis with seizure or headache or both intracranial intracranial processprocessDiarrhea, emesis, & fever Diarrhea, emesis, & fever gastroenteritis. gastroenteritis.Fever, abdominal pain, & emesis Fever, abdominal pain, & emesis appendicitis appendicitisBilious emesis & abdominal pain Bilious emesis & abdominal pain I.O. I.O.

Differential Dx of GERDifferential Dx of GER

Most cases of emesisMost cases of emesis are caused by GER, acute are caused by GER, acute gastroenteritis, or systemic disorders such as tonsillitis, gastroenteritis, or systemic disorders such as tonsillitis, otitis media, or urinary tract infectionotitis media, or urinary tract infectionThe differential diagnosis for GER in the The differential diagnosis for GER in the adolescentadolescent may may include pneumonia, costochondritis, pericarditis, include pneumonia, costochondritis, pericarditis, pulmonary embolism, arrhythmias, ischemia due to an pulmonary embolism, arrhythmias, ischemia due to an anomalous coronary artery, pancreatitis, cholecystitis, anomalous coronary artery, pancreatitis, cholecystitis, peptic ulcer disease, and anxietypeptic ulcer disease, and anxietyIn the older child, GER is often manifested as epigastric In the older child, GER is often manifested as epigastric abdominal or chest pain. Define the pain's location and abdominal or chest pain. Define the pain's location and severity and whether it radiates and is constant or severity and whether it radiates and is constant or intermittent. Burning epigastric or chest pain is probably intermittent. Burning epigastric or chest pain is probably reflux in the adolescent, especially if it occurs after meals reflux in the adolescent, especially if it occurs after meals when the patient lies down.when the patient lies down.

Differential Dx of GERDifferential Dx of GER

GERD vs DyspepsiaGERD vs Dyspepsia

Distinguish from DyspepsiaDistinguish from Dyspepsiao Ulcer-like symptoms-burning, epigastric Ulcer-like symptoms-burning, epigastric

painpaino Dysmotility like symptoms-nausea, Dysmotility like symptoms-nausea,

bloating, early satiety, anorexiabloating, early satiety, anorexia Distinct clinical entityDistinct clinical entity In addition to antisecretory meds and In addition to antisecretory meds and

an EGD need to consider an evaluation an EGD need to consider an evaluation for Helicobacter pylorifor Helicobacter pylori

• Very often physiological, esp < 6 moVery often physiological, esp < 6 mo

• 90% resolve <12-18mo90% resolve <12-18mo

• Vomiting > 2 yr age never Vomiting > 2 yr age never physiologicalphysiological

• GERD usually a chronic, relapsing GERD usually a chronic, relapsing disease with waxing & waningdisease with waxing & waning

•Completely resolving in no more than Completely resolving in no more than halfhalf

• Very often physiological, esp < 6 moVery often physiological, esp < 6 mo

• 90% resolve <12-18mo90% resolve <12-18mo

• Vomiting > 2 yr age never Vomiting > 2 yr age never physiologicalphysiological

• GERD usually a chronic, relapsing GERD usually a chronic, relapsing disease with waxing & waningdisease with waxing & waning

•Completely resolving in no more than Completely resolving in no more than halfhalf

< 2 yr age< 2 yr age< 2 yr age< 2 yr age

> 2yr age > 2yr age adulthood adulthood> 2yr age > 2yr age adulthood adulthood

Carre NelsonCarre NelsonCarre NelsonCarre Nelson

GER: Natural History

INDICATIONS FOR INVESTIGATIONINDICATIONS FOR INVESTIGATIONSuspicion of ComplicationSuspicion of Complication

INDICATIONS FOR INVESTIGATIONINDICATIONS FOR INVESTIGATIONSuspicion of ComplicationSuspicion of Complication

• Irritability with feedsIrritability with feeds

• Recurrent pneumonias / chronic coughRecurrent pneumonias / chronic cough

• Generally unhappy babyGenerally unhappy baby

• Failing to thriveFailing to thrive

• Torticollis [?Sandifer’s syndrome]Torticollis [?Sandifer’s syndrome]

• Persistent vomiting at 18-24moPersistent vomiting at 18-24mo

• Irritability with feedsIrritability with feeds

• Recurrent pneumonias / chronic coughRecurrent pneumonias / chronic cough

• Generally unhappy babyGenerally unhappy baby

• Failing to thriveFailing to thrive

• Torticollis [?Sandifer’s syndrome]Torticollis [?Sandifer’s syndrome]

• Persistent vomiting at 18-24moPersistent vomiting at 18-24mo

GER: Approach in < 2 yrs age

INDICATIONS FOR INVESTIGATIONINDICATIONS FOR INVESTIGATIONINDICATIONS FOR INVESTIGATIONINDICATIONS FOR INVESTIGATION

•Persistence of vomiting since < 2yrsPersistence of vomiting since < 2yrs•New onset recurrent vomitingNew onset recurrent vomiting•Suspicion of a complicationSuspicion of a complicationo undiagnosed anemiaundiagnosed anemiao dysphagia / odynophagiadysphagia / odynophagiao recurrent pneumonias, coughrecurrent pneumonias, cougho nonseasonal asthmanonseasonal asthma

•Persistence of vomiting since < 2yrsPersistence of vomiting since < 2yrs•New onset recurrent vomitingNew onset recurrent vomiting•Suspicion of a complicationSuspicion of a complicationo undiagnosed anemiaundiagnosed anemiao dysphagia / odynophagiadysphagia / odynophagiao recurrent pneumonias, coughrecurrent pneumonias, cougho nonseasonal asthmanonseasonal asthma

GER: Approach in > 2 yrs age

InvestigationsInvestigations

• CBC: NormalCBC: Normal

•Electrolytes: hypochloremic, hypokalemic Electrolytes: hypochloremic, hypokalemic metabolic alkalosis with severe refluxmetabolic alkalosis with severe reflux

•CXR: for aspiration pneumonia & changes due CXR: for aspiration pneumonia & changes due to recurrent aspirationto recurrent aspiration

•UPPER GI CONTRAST STUDYUPPER GI CONTRAST STUDY

- not a test for reflux- not a test for reflux

- stricture / achalasia / mass- stricture / achalasia / mass

- - road maproad map

• UPPER GI ENDOSCOPY, BIOPSIESUPPER GI ENDOSCOPY, BIOPSIES

• 24HR INTRAESOPHAGEAL pH24HR INTRAESOPHAGEAL pH

•GASTRIC EMPTYING STUDYGASTRIC EMPTYING STUDY

• CBC: NormalCBC: Normal

•Electrolytes: hypochloremic, hypokalemic Electrolytes: hypochloremic, hypokalemic metabolic alkalosis with severe refluxmetabolic alkalosis with severe reflux

•CXR: for aspiration pneumonia & changes due CXR: for aspiration pneumonia & changes due to recurrent aspirationto recurrent aspiration

•UPPER GI CONTRAST STUDYUPPER GI CONTRAST STUDY

- not a test for reflux- not a test for reflux

- stricture / achalasia / mass- stricture / achalasia / mass

- - road maproad map

• UPPER GI ENDOSCOPY, BIOPSIESUPPER GI ENDOSCOPY, BIOPSIES

• 24HR INTRAESOPHAGEAL pH24HR INTRAESOPHAGEAL pH

•GASTRIC EMPTYING STUDYGASTRIC EMPTYING STUDY

Contrast Studies for GER

Gastrografin Gastrografin (Diatrizoate Meglumine & Diatrizoate Sodium (Diatrizoate Meglumine & Diatrizoate Sodium Solution) is a Solution) is a palatablepalatable lemon-flavored lemon-flavored water-soluble water-soluble iodinatediodinated radiopaque contrast medium radiopaque contrast mediumFollowing oral administration only about 3% is absorbed Following oral administration only about 3% is absorbed from the stomach and intestinesfrom the stomach and intestinesIn children up to 10 years of age, 15-30 mL is generally In children up to 10 years of age, 15-30 mL is generally sufficient. This dose can be diluted with twice its volume of sufficient. This dose can be diluted with twice its volume of water. For babies and young children it is recommended water. For babies and young children it is recommended that the contrast medium be diluted with 3 times its volume that the contrast medium be diluted with 3 times its volume of waterof waterNot to be administered to patients who are hypersensitive Not to be administered to patients who are hypersensitive to iodine (C.I. in hyperthyroid)to iodine (C.I. in hyperthyroid)

Contrast Studies for GER

AspirationAspiration of Gastrografin into the trachea and airways of Gastrografin into the trachea and airways may result in serious pulmonary complications including, may result in serious pulmonary complications including, pulmonary edemapulmonary edema, pneumonitis or death Bronchial entry of , pneumonitis or death Bronchial entry of any orally administered contrast medium causes a copious any orally administered contrast medium causes a copious osmotic effusion. Therefore, osmotic effusion. Therefore, avoid use of Gastrografin in avoid use of Gastrografin in patients with tracheo-esophageal fistulapatients with tracheo-esophageal fistula and minimize risks and minimize risks for pulmonary aspiration in all patients.for pulmonary aspiration in all patients.Anaphylactic reactions, including fatalities, have been Anaphylactic reactions, including fatalities, have been reported with the use of Gastrografin. Patients at increased reported with the use of Gastrografin. Patients at increased risk include those with a history of a previous reaction to a risk include those with a history of a previous reaction to a contrast medium, patients with a known sensitivity to contrast medium, patients with a known sensitivity to iodine, and patients with a known clinical hypersensitivity iodine, and patients with a known clinical hypersensitivity (bronchial asthma, hay fever, and food allergies)(bronchial asthma, hay fever, and food allergies)

Contrast Studies for GER

An upper GI An upper GI BARIUM STUDYBARIUM STUDY, although no longer the , although no longer the diagnostic study of choice, may be useful.diagnostic study of choice, may be useful.The sensitivity in diagnosing the occurrence of reflux and The sensitivity in diagnosing the occurrence of reflux and the presence of esophagitis is low, but esophageal the presence of esophagitis is low, but esophageal motility motility and anatomic abnormalitiesand anatomic abnormalities (e.g., hiatal hernia, achalsia, (e.g., hiatal hernia, achalsia, stricture, malrotation, GOO) may be identified. stricture, malrotation, GOO) may be identified. Helps to plan surgical interventionHelps to plan surgical intervention, if required (cf. Milk , if required (cf. Milk Scan)Scan)Less palatableLess palatable, hence difficult to use in young children, hence difficult to use in young childrenBoth an upper GI barium study and GE scintigraphy may Both an upper GI barium study and GE scintigraphy may be helpful in the diagnosis of GER but are not sensitive. The be helpful in the diagnosis of GER but are not sensitive. The primary diagnostic tool for GER today is the pH probe primary diagnostic tool for GER today is the pH probe study. Impedance/pH monitoring is currently under study. Impedance/pH monitoring is currently under investigation as a potentially superior diagnostic modality. investigation as a potentially superior diagnostic modality.

Contrast Studies for GER

Contrast Studies for GER

Milk Scan: Gastric emptying scintigraphyMilk Scan: Gastric emptying scintigraphyInvolves ingestion of a Involves ingestion of a radiolabeled (Tc99m) meal/ milkradiolabeled (Tc99m) meal/ milk, , with serial images recorded up to 60 minutes after with serial images recorded up to 60 minutes after ingestion. This study may be used to diagnose and ingestion. This study may be used to diagnose and quantitate reflux but is primarily used to assess quantitate reflux but is primarily used to assess gastric gastric emptyingemptying and to identify delayed GE. and to identify delayed GE.

Late images showing isotope in the lungs indicate Late images showing isotope in the lungs indicate pulmonary aspiration. pulmonary aspiration.

No sedation / prolonged observation / high sensitivity / low No sedation / prolonged observation / high sensitivity / low radiation exposureradiation exposure

Procedure: burped and placed supine, anterior and Procedure: burped and placed supine, anterior and posterior imaging of abdomen / thorax / mouthposterior imaging of abdomen / thorax / mouth

pH Monitoring

The 24-hour pH probe monitor is the The 24-hour pH probe monitor is the gold standardgold standard for Dx for DxA catheter at the LES measures episodes of reflux over a A catheter at the LES measures episodes of reflux over a 24-hour period: 24-hour period: requires hospitalizationrequires hospitalizationAn esophageal intraluminal An esophageal intraluminal pH < 4.0pH < 4.0 for at least 15 for at least 15 seconds defines an episode of refluxseconds defines an episode of refluxRecorded values include Recorded values include total time with pHtotal time with pH below 4.0, below 4.0, upright time with pHupright time with pH less than 4.0, less than 4.0, supine time with pHsupine time with pH less less than 4.0, number of reflux than 4.0, number of reflux episodes longer than 5 minutesepisodes longer than 5 minutes, , and and duration of the longestduration of the longest reflux episode. reflux episode.DisadvantagesDisadvantages: inability to diagnose nonacid reflux and to : inability to diagnose nonacid reflux and to distinguish primary and secondary (allergy to milk protein distinguish primary and secondary (allergy to milk protein or other food) causes of reflux, the inability to determine the or other food) causes of reflux, the inability to determine the presence or severity of esophagitis, and poor tolerance of presence or severity of esophagitis, and poor tolerance of the probe in some childrenthe probe in some children

Impedance Monitoring

Esophageal impedance/pH monitoring is a novel technique Esophageal impedance/pH monitoring is a novel technique that can be used that can be used to detect both acid and nonacid refluxto detect both acid and nonacid reflux..This test uses a probe similar to that used in standard pH This test uses a probe similar to that used in standard pH monitoring to measure the change in electrical resistance monitoring to measure the change in electrical resistance that occurs across its sensors with the passage of that occurs across its sensors with the passage of intraluminal materialintraluminal materialAdvantages of this test include the ability to identify the Advantages of this test include the ability to identify the content, direction, and localization of any refluxcontent, direction, and localization of any reflux. This test . This test may yield may yield better diagnostic sensitivity than pH probebetter diagnostic sensitivity than pH probe in in patients treated with antacidspatients treated with antacidsDisadvantages include a Disadvantages include a lack of standardized pediatric lack of standardized pediatric normal rangesnormal ranges and increased cost relative to standard pH and increased cost relative to standard pH probeprobeInvestigational toolInvestigational tool

Endoscopy

Endoscopy is used to visualize and obtain a biopsy sample Endoscopy is used to visualize and obtain a biopsy sample from the esophageal mucosa and to from the esophageal mucosa and to diagnose esophagitis, diagnose esophagitis, stricture, & Barrett esophagusstricture, & Barrett esophagus..

Although there is no validated grading system for children, Although there is no validated grading system for children, erosion or ulceration is indicative of esophagitiserosion or ulceration is indicative of esophagitis

BiopsyBiopsy should be performed in most cases, even if the should be performed in most cases, even if the mucosa appears relatively normalmucosa appears relatively normal, because there is a , because there is a significant tendency for histologic grade to exceed visual significant tendency for histologic grade to exceed visual endoscopic findingsendoscopic findings

Endoscopic ultrasonography has been described as an Endoscopic ultrasonography has been described as an adjunct to endoscopy to evaluate the integrity of Nissen adjunct to endoscopy to evaluate the integrity of Nissen fundoplication in children and adultsfundoplication in children and adults

Goals Eliminate symptoms

Manage or prevent complications

Prevent relapse Heal esophageal mucosa

Treatment Goals of GERDTreatment Goals of GERD

Pediatric GERD

Adult GERD

Treatment of childhood GERD results in Treatment of childhood GERD results in betterbetter

disease disease outcomeoutcome in adults! in adults!

Treatment Goals of GERDTreatment Goals of GERD

• Explanation, reassuranceExplanation, reassurance

• Diet, lifestyleDiet, lifestyle

• PositionPosition

• AntacidsAntacids

• Anticholinergics [e.g., Anticholinergics [e.g., XXbethanecolbethanecolXX]]

• Prokinetics [Prokinetics [XXmetoclopramidemetoclopramideXX, , XXcisapridecisaprideXX] ]

• H2-Receptor AntagonistsH2-Receptor Antagonists

• PPIPPI

• Antireflux-SurgeryAntireflux-Surgery

• Explanation, reassuranceExplanation, reassurance

• Diet, lifestyleDiet, lifestyle

• PositionPosition

• AntacidsAntacids

• Anticholinergics [e.g., Anticholinergics [e.g., XXbethanecolbethanecolXX]]

• Prokinetics [Prokinetics [XXmetoclopramidemetoclopramideXX, , XXcisapridecisaprideXX] ]

• H2-Receptor AntagonistsH2-Receptor Antagonists

• PPIPPI

• Antireflux-SurgeryAntireflux-Surgery

Management

Small frequent feedsSmall frequent feeds

Thickening of milk feeds (1 TBS of rice cereal Thickening of milk feeds (1 TBS of rice cereal per oz of formula)per oz of formula)

Avoid overfeedingAvoid overfeeding

Holding upright and burping: prone head-up Holding upright and burping: prone head-up position for position for at least 20 minutes after a feedingat least 20 minutes after a feeding

Avoid tight clothing and passive smokingAvoid tight clothing and passive smoking

A short trial of a A short trial of a hypoallergenic diethypoallergenic diet can be can be used to exclude milk or soy protein allergy used to exclude milk or soy protein allergy before pharmacotherapybefore pharmacotherapy

Lifestyle Changes in Infant with GERLifestyle Changes in Infant with GER

Post-feed Positioning

Right-side lying position after feeding: NeonatesRight-side lying position after feeding: Neonates

Whaley & Wong’s Essentials of Pediatric Nursing, 5th Ed, Mosby, 1997

No food or drink for 2 hours before bed-timeNo food or drink for 2 hours before bed-time

Elevate head of bed (6’’) if nocturnal symptomsElevate head of bed (6’’) if nocturnal symptoms

Avoid foods (caffeine, chocolates, spicy or fatty foods, Avoid foods (caffeine, chocolates, spicy or fatty foods, citrus foods, tomato, carbonated beverages)citrus foods, tomato, carbonated beverages)

Weight loss if overweightWeight loss if overweight

Avoidance of smoking and alcoholAvoidance of smoking and alcohol

The efficacy of positioning for older children is unclear, The efficacy of positioning for older children is unclear, but some evidence suggests a benefit to but some evidence suggests a benefit to left side positionleft side position & head elevation during sleep& head elevation during sleep

Lifestyle Changes in Older Children with Lifestyle Changes in Older Children with GERGER

GER Bed

Elevation

Stomach acid

remains down

Directed at Directed at ameliorating the acidityameliorating the acidity of the gastric contents or at of the gastric contents or at promoting their aboral movementpromoting their aboral movementAcid ReducersAcid Reducers

o AntacidsAntacids

o HH22 receptor antagonists-ranitidine,famotidine receptor antagonists-ranitidine,famotidine

o Proton pump inhibitors (PPIs) –omeprazole, lansoprazole Proton pump inhibitors (PPIs) –omeprazole, lansoprazole ProkineticsProkinetics

o Cisapride Cisapride

o MetoclopramideMetoclopramide

o DomperidoneDomperidone

Acid suppression is the mainstay of GERD management in both children and adults1

1.Aliment Pharmacol Ther 2004; 19 (suppl 1) 22-27

Pharmacologic Therapy of GERD Pharmacologic Therapy of GERD

e.g. metoclopramide (dopamine-2 and 5HT-3 e.g. metoclopramide (dopamine-2 and 5HT-3 antagonist), bethanechol (cholinergic agonist), antagonist), bethanechol (cholinergic agonist), and erythromycin (motilin receptor agonist) & and erythromycin (motilin receptor agonist) & cisapridecisaprideAct on through their effects on LES pressure, Act on through their effects on LES pressure, esophageal peristalsis or clearance and/or esophageal peristalsis or clearance and/or gastric emptying, gastric emptying, No effect on TLESRNo effect on TLESRNoNo clear scientific evidence on clear scientific evidence on efficacyefficacyNot US FDA approvedNot US FDA approved for GERD in children for GERD in childrenCisapride-cardiac side effect: BannedCisapride-cardiac side effect: BannedMetaclopramide- extra pyramidal side effects Metaclopramide- extra pyramidal side effects (>20%)(>20%)

ProkineticsProkinetics

Rapid but transient reliefRapid but transient relief of symptoms by acid of symptoms by acid neutralizationneutralizationNo role on source of acid secretionNo role on source of acid secretionNeeds to be given more than 6 Needs to be given more than 6 dosesdoses per day per dayCan not be used for a prolonged period because Can not be used for a prolonged period because of side effects of diarrhea (magnesium) and of side effects of diarrhea (magnesium) and constipation (aluminum) and rare reports of more constipation (aluminum) and rare reports of more serious side effects of chronic useserious side effects of chronic useAluminium containing antacids may cause Aluminium containing antacids may cause aluminium aluminium toxicitytoxicityOccasional formation of large bezoar-like Occasional formation of large bezoar-like masses of agglutinated intragastric materialmasses of agglutinated intragastric material

Antacids (Alginate-)Antacids (Alginate-)

Acid-suppressant therapy is recommended in Acid-suppressant therapy is recommended in severe esophagitis, but this does not rectify severe esophagitis, but this does not rectify primary disordered motility, a major primary disordered motility, a major pathophysiological mechanismpathophysiological mechanismDefinite benefit in treatment of Definite benefit in treatment of mild-to-moderate mild-to-moderate reflux esophagitisreflux esophagitis. H2RAs have been . H2RAs have been recommended as recommended as first-line therapyfirst-line therapy because of because of their excellent overall safety profile, but they are their excellent overall safety profile, but they are being being superseded bysuperseded by PPI in this role, as PPI in this role, as increased experience with pediatric use and increased experience with pediatric use and safetysafetyLess potentLess potent compared to PPI compared to PPIAssociated with Associated with tachyphylaxistachyphylaxisDrugs: cimetidine, famotidine, nizatidine, & ranitidineDrugs: cimetidine, famotidine, nizatidine, & ranitidine

H2RAsH2RAs

Provide the Provide the most potent antireflux effectmost potent antireflux effect by by blocking the blocking the H+,K+-ATPase (proton pump) H+,K+-ATPase (proton pump) channels of the final common pathway in gastric channels of the final common pathway in gastric acid secretionacid secretionIn typical doses, diminish the daily production In typical doses, diminish the daily production of acid (basal and stimulated) by 80–95%of acid (basal and stimulated) by 80–95%PPIs are superior to H2RAs in the treatment of PPIs are superior to H2RAs in the treatment of severe and erosivesevere and erosive esophagitis esophagitisAll proton pump inhibitors have All proton pump inhibitors have equivalent equivalent efficacyefficacy at comparable doses at comparable dosesAn acidic pH is required for drug activation, & An acidic pH is required for drug activation, & since food stimulates acid production, these since food stimulates acid production, these drugs ideally should be drugs ideally should be given about 30 minutes given about 30 minutes before mealsbefore meals

PPIPPI

Younger patients generally have increased Younger patients generally have increased metabolic capacity, resulting in the need for metabolic capacity, resulting in the need for higher dosages of PPI per Kghigher dosages of PPI per Kg in children in children compared to adultscompared to adultsGenerally cause remarkably Generally cause remarkably few adverse few adverse effectseffects. The most common are nausea, . The most common are nausea, abdominal pain, constipation, flatulence, & abdominal pain, constipation, flatulence, & diarrhea. Subacute myopathy, arthralgias, diarrhea. Subacute myopathy, arthralgias, headaches, and rashes also have been reportedheadaches, and rashes also have been reportedCan Can interact interact with warfarin (esomeprazole, lansoprazole, with warfarin (esomeprazole, lansoprazole, omeprazole, & rabeprazole), diazepam (esomeprazole & omeprazole, & rabeprazole), diazepam (esomeprazole & omeprazole), & cyclosporine (omeprazole and omeprazole), & cyclosporine (omeprazole and rabeprazole). Omeprazole inhibits CYP2C19 (thereby rabeprazole). Omeprazole inhibits CYP2C19 (thereby decreasing the clearance of disulfiram, phenytoin, and decreasing the clearance of disulfiram, phenytoin, and other drugs) and induces the expression of CYP1A2 other drugs) and induces the expression of CYP1A2 (thereby increasing the clearance of imipramine, several (thereby increasing the clearance of imipramine, several antipsychotic drugs, tacrine, and theophylline)antipsychotic drugs, tacrine, and theophylline)

PPIPPI

Prolonged useProlonged use of PPIs can result in vitamin of PPIs can result in vitamin B12 B12 deficiencydeficiency as a consequence of impaired release as a consequence of impaired release of vitamin B12 from food in a non-acid of vitamin B12 from food in a non-acid environmentenvironmentPotential consequences of prolonged acid Potential consequences of prolonged acid suppression, include the risk of proliferation of suppression, include the risk of proliferation of gastric flora and the risk of developing gastric flora and the risk of developing enterochromaffin-like cell hyperplasia, enterochromaffin-like cell hyperplasia, ((hypergastrinemiahypergastrinemia) ) gastric malignancy gastric malignancy

PPIPPI

Expect response in Expect response in 2-4 weeks2-4 weeks (whether using (whether using H2RA or PPI) H2RA or PPI) If no response If no response Change from H2RA to PPI Change from H2RA to PPIIf no response If no response Maximize dose of PPI Maximize dose of PPITherapy indicated for a minimum of Therapy indicated for a minimum of 8-12 weeks8-12 weeksIf PPI If PPI response inadequateresponse inadequate despite maximal despite maximal dosage, dosage, confirmconfirm diagnosis : EGD, 24 hour pH diagnosis : EGD, 24 hour pH monitormonitorFailure to control symptoms with high-dose PPI Failure to control symptoms with high-dose PPI treatment raises the likelihood of treatment raises the likelihood of non-acid-non-acid-related causesrelated causes for the symptoms for the symptoms

PPI TrialPPI Trial

MedicationMedication DoseDose FrequencyFrequencyHH22RAsRAs

FamotidineFamotidine 1 mg/kg/day1 mg/kg/day Twice dailyTwice daily

RanitidineRanitidine 5-10 mg/kg/day5-10 mg/kg/day Twice daily or thrice dailyTwice daily or thrice daily

PPIsPPIs

LansoprazoleLansoprazole 0.4-2.8 mg/kg/day0.4-2.8 mg/kg/day30 Kg: 15 mg/d30 Kg: 15 mg/d> 30 Kg: 30 mg/d> 30 Kg: 30 mg/d

Once dailyOnce daily > 1 yr> 1 yr

OmeprazoleOmeprazole 0.2-3.5 mg/kg/day0.2-3.5 mg/kg/day< 10 Kg: 10 mg/d< 10 Kg: 10 mg/d 10 Kg: 20 mg/d10 Kg: 20 mg/d

Once dailyOnce daily > 2 yr> 2 yr

PantoprazolePantoprazole 20-40 mg/day, 0.5 -1 20-40 mg/day, 0.5 -1 mg/kg/dmg/kg/d

> 5 yr> 5 yr

EsomeprazoleEsomeprazole < 20 kg: 10 mg< 20 kg: 10 mg≥ ≥ 20 kg: 20 mg20 kg: 20 mg

> 1 yr> 1 yr

PPI DosesPPI Doses

At the end of 12 weeks of the treatment period, 70-75% of children At the end of 12 weeks of the treatment period, 70-75% of children had resolution or improvement in their overall symptoms.had resolution or improvement in their overall symptoms.During the first 2 weeks of treatment, there was significant During the first 2 weeks of treatment, there was significant reduction in the average severity of GERD.reduction in the average severity of GERD.Percentage of days antacid used is reduced from 50% at Percentage of days antacid used is reduced from 50% at pretreatment period to 0 in last week.pretreatment period to 0 in last week.By end of the therapy there is healing of lesions of erosive By end of the therapy there is healing of lesions of erosive esophagitis in 95-100% of cases.esophagitis in 95-100% of cases.At the end of 12 weeks of the treatment period, 79% of children At the end of 12 weeks of the treatment period, 79% of children had resolution or improvement in cough and 63% in wheeze.had resolution or improvement in cough and 63% in wheeze.92% of children were highly compliant.92% of children were highly compliant.Healthy children preferred the taste of strawberry flavoured Healthy children preferred the taste of strawberry flavoured lansoprazole ODT to the peppermint flavoured ranitidine syrup.lansoprazole ODT to the peppermint flavoured ranitidine syrup.

J Pediatr Gastroenterol Nutr 2002; 35: 308-317,J Pediatr Gastroenterol Nutr 2005; 40: 319 - 327

PPI: Highlights of Clinical StudiesPPI: Highlights of Clinical Studies

Protocol for Management

Am Fam Physician. 2001Am Fam Physician. 2001

Protocol for Management

Initiate Tx with H2RA or PPIInitiate Tx with H2RA or PPI

H2RA taken H2RA taken BIDBID

Good responseGood response

Frequent relapsesFrequent relapses

On demand TxOn demand Tx

PPI taken QDPPI taken QD

Good responseGood response

Maintenance therapyMaintenance therapywith lowest effective dosewith lowest effective dose

Symptoms persistSymptoms persist

Consider EGD if Consider EGD if risk factors presentrisk factors present((>> 45, white, male 45, white, maleand > 5 yrs of sx)and > 5 yrs of sx)

Increase toIncrease tomax dose QD max dose QD or BIDor BID

Good responseGood response

Confirm diagnosisConfirm diagnosisEGD, ph monitorEGD, ph monitor

NoNo

YesYes YesYesNoNo

YesYes

YesYes

NoNo

NoNo

Surgery: Nissen FundoplicationSurgery: Nissen Fundoplication

Effective therapy for Effective therapy for intractable GERDintractable GERD in in children, particularly those with refractory children, particularly those with refractory esophagitis or strictures and those at risk for esophagitis or strictures and those at risk for significant morbidity from chronic pulmonary significant morbidity from chronic pulmonary diseasediseaseIt may be combined with a gastrostomy for It may be combined with a gastrostomy for feeding or ventingfeeding or ventingLong-term studies suggest that Long-term studies suggest that fundoplications fundoplications frequently become incompetentfrequently become incompetent in children, as in adults; this fact currently in children, as in adults; this fact currently combines with the potency of PPI therapy that is combines with the potency of PPI therapy that is now available to shift practice toward long-term now available to shift practice toward long-term pharmacotherapy in many cases.pharmacotherapy in many cases.

Surgery: Nissen FundoplicationSurgery: Nissen Fundoplication

Even those patients who do not fully respond to medical Even those patients who do not fully respond to medical management should be management should be treated for 8 weekstreated for 8 weeks before before surgical therapy is considered, unless the patient is surgical therapy is considered, unless the patient is experiencing life-threatening symptoms!experiencing life-threatening symptoms!

PPI: LansoprazolePPI: Lansoprazole

Peptic ulcer (duodenal ulcer, gastric ulcer)Peptic ulcer (duodenal ulcer, gastric ulcer)Drug induced gastritis (anti TB, antimalarial, Drug induced gastritis (anti TB, antimalarial, antibiotics)antibiotics)ICU patients to avoid stress induced ulcerICU patients to avoid stress induced ulcerH. pylori gastritisH. pylori gastritisGERD in children with cerebral palsyGERD in children with cerebral palsyResistant asthmaResistant asthma

Contraindications:Contraindications: in patients with known in patients with known hypersensitivity to any component of the hypersensitivity to any component of the formulation of Lansoprazoleformulation of Lansoprazole

Lansoprazole: Other indicationsLansoprazole: Other indications

Renal impairmentRenal impairment: No dosage adjustment appears : No dosage adjustment appears necessary for patients with renal impairment necessary for patients with renal impairment

HepaticHepatic impairment impairment: In: In adults, dosage of PPI should beadults, dosage of PPI should be reduced by 50%reduced by 50% . PPI disposition in children has never . PPI disposition in children has never been studiedbeen studied

PregnancyPregnancy: This: This drug should be useddrug should be used during during pregnancy only if clearly neededpregnancy only if clearly needed

Lactation: BreastLactation: Breast-feeding should be discontinued if the -feeding should be discontinued if the use of lansoprazole is considered essential use of lansoprazole is considered essential

PPI: Warnings & PrecautionsPPI: Warnings & Precautions

Generally Generally well toleratedwell tolerated 15% of children experience side effects, 15% of children experience side effects,

which are mild to moderate in naturewhich are mild to moderate in nature GI events (nausea, vomiting, diarrhea, GI events (nausea, vomiting, diarrhea,

constipation) and headache are common constipation) and headache are common side effectsside effects

No clinically significant changes in No clinically significant changes in hematological and biochemical parametershematological and biochemical parameters

Drugs 2005; 65:2129-35Drugs 2005; 65:2129-35

PPI: Side Effects LansoprazolePPI: Side Effects Lansoprazole

Contains 15/30 mg of LansoprazoleContains 15/30 mg of Lansoprazole Available in orally disintegrating tablet form Available in orally disintegrating tablet form

(ODT), Strawberry flavored (ODT), Strawberry flavored Junior Lanzol should not be chewedJunior Lanzol should not be chewed Tablet should be placed on the tongue and Tablet should be placed on the tongue and

allowed to disintegrate with or without waterallowed to disintegrate with or without water Can also be administered with a spoon: Can also be administered with a spoon:

Place the tablet in a teaspoon or two 15 mg Place the tablet in a teaspoon or two 15 mg tablets in a tablespoon of water & wait till tablets in a tablespoon of water & wait till tablet/tablets get disintegratedtablet/tablets get disintegrated

Lansoprazole: Junior LanzolLansoprazole: Junior Lanzol

Key Points

• GER can be physiological or GER can be physiological or pathological (GERD)pathological (GERD)

•Physiologic resolves by the age Physiologic resolves by the age of 24 months in most casesof 24 months in most cases

• Medical management remains Medical management remains the mainstay of treatmentthe mainstay of treatment

• GER should be looked for in GER should be looked for in cases of resistant asthmacases of resistant asthma

• GER can be physiological or GER can be physiological or pathological (GERD)pathological (GERD)

•Physiologic resolves by the age Physiologic resolves by the age of 24 months in most casesof 24 months in most cases

• Medical management remains Medical management remains the mainstay of treatmentthe mainstay of treatment

• GER should be looked for in GER should be looked for in cases of resistant asthmacases of resistant asthma