Gastroesophageal reflux in children - Zhejiang...
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Gastroesophageal reflux in children
浙江大学医学院附属儿童医院
江米足
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Definition of GER or GERD GER: means involuntary passage of
gastric contents into the esophagus and is often physiological.
GERD: means symptoms or complications associated with pathological GER.
Hassall E. Arch Dis Child 2005
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Prevalence USA:
3-9 y:566 cases, 1.8% 10-17 y:615 cases, 3.5% Adults (>18 y):22%
The prevalence of GERD slowly increases with age during childhood and becomes quite frequent among young adults.
Nelson SP, et al. Arch Pediatr Adolesc Med 2000
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Prevalence Australia:863
infants 3-4m(41%) 13-14m(<5%)
India:602 infants 1-6m(55%) 7-12m(15%) 12-24m(10%)
Italy:2642 infants 0-12m (12%)
Martin AJ, et al. Pediatrics 2002Campanozzi A et al. Pediatrics 2009De S, et al. Trop Gastroenterol 2001
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Prevalence GER is frequently seen in early infancy and it
almost disappears by one year of age. Persistence or appearance of regurgitation
beyond 18 months of age is suggestive of pathological condition.
The prevalence of GERD in infancy is 5%-9% of all infants with regurgitation.
Poddar U. Indian Pediatr 2013
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Anti-reflux mechanism
Liu XL, et al. Hong Kong Med J 2012
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Closing mechanisms The diaphragm creates a pinch cork action and
functions to increase the pressure The intra-abdominal portion of the esophagus The angle of His between the stomach and the
esophagus Opening mechanisms
Increased intra-abdominal pressure (from abdominal tumours, coughing, and constipation) increases intra-gastric pressure
Liu XL, et al. Hong Kong Med J 2012
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Risk factors of GER Poor function of LES (pressure and length) Esophageal dysmotility resulting in
reduced clearance Abnormal anatomy-including congenital
malformation (short intra-abdominal esophagus) or acquired disease (esophageal atresia repair)
Higher intra-gastric pressure and delayed gastric emptying
Liu XL, et al. Hong Kong Med J 2012
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Transient lower esophageal sphincter relaxations (TLESR)
TLESR
cc
GER
TLESR is defined as an abrupt decrease in LES pressure to the level of the intra-gastric pressure unrelated to swallowing, with a relatively longer duration (8-10 s) than seen with relaxations triggered by a swallow
Omari TI, et al. Gut 2002
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TLESR
Omari TI, et al. Gut 2002
TLESR is the predominant mechanism of GER triggering, accounting for 50-100% (median 91.5%) of all GER episodes.
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Clinical symptoms of GER Clinical features of GER vary in children of
different ages. Typical symptoms
Regurgitation Vomiting Heartburn Chest pain
Atypical symptoms Feeding difficulties/anorexia Failure to thrive Postural defect Stridor Chronic cough Laryngitis, otitis Asthma sinusitis Martigne L, et al. Eur J Pediatr 2012
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Yuksel ES, et al. Eur J Med Sci 2010
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Laryngeal findings in reflux laryngitis
Kamal A, et al. Best Practice Res Clin Gastroenterol 2010
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Presenting symptoms Regurgitation or vomiting
Healthy: no failure to thrive or other associated symptoms
Infants with GERD Growth failure or indirect symptoms of pain due to
esophagitis like irritability, feeding difficulty, sleeping difficulties, crying episodes, anemia
Rarely apnea or ALTE Chronic respiratory diseases and upper airway
problems like sinusitis, otitis media, laryngitis, dental erosion
In children and adolescents, symptoms and complications of GERD are heartburn or substernal pain
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Presenting symptoms of GERDInfants Children
Vomiting Regurgitation
Poor weight gain Anemia and hematemesis
Irritability Heartburn and retrosternal chest pain
Feeding refusal or dysphagia Dysphagia
Recurrent pneumonia Recurrent pneumonia
Asthma and upper airway symptoms
Asthma or chronic cough
Apnea or apparent life-threatening event (ALTE)
Michail S. Pediatr Review 2007
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Diagnostic test Esophageal pH monitoring Multichannel intraluminal impedance (MII)
measurement High resolution manometry (HRM) Endoscopy Confocal laser endomicroscopy Barium UGI series Nuclear scintigraphy GER questionnaire Rome III criteria
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Esophageal pH monitoring To establish the presence of acidic reflux
(pH<4) To quantify reflux in patients with mainly
extra-esophageal symptoms To assess the efficacy of medical therapy To measure GER in patients not
responding to antireflux treatment and in research
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24 hr ambularoty pH-metry
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Parameters of pH monitoring Percent total time with a pH<4.0 (reflux
index, RI) Percent upright time with a pH<4.0 Percent supine time with a pH<4.0 Number of reflux episodes Number of reflux episodes lasting≥5 min Longest reflux episode (min) The scoring system
Boix-Ochoa score Demeester score
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Esophageal pH monitoring Advantages
Be done in any age Be relatively non-invasive
Disadvantage Does not measure non-acid or weakly acidic
reflux
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Multichannel intraluminal-impedance (MII) measurement To detect the change in electrical
resistance (or impedance) when substances pass through the esophagus using a series of impedance sensors lying 1 cm apart on a probe
Impedance is inversely proportional to electrical conductivity
Since the conductivity of liquid (high) and air (low) is different, MII can easily differentiate liquid from gas reflux
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z
The basic principle of impedance measurement
Inversely proportional to conductivity of luminal contents
0
2000
Refluxate
Food
Saliva
Air
Low conductivity = High Ω
High conductivity = Low Ω
Ω
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van Wijk MP, et al. J Pediatr Gastroenterol Nutr 2009
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TLESR
4
pH
10sec
Z
Z
Z
Z
Z
Z
Z
Z
Z
Z
Z
Z
pH
4
pH
MII-pH monitoring (acid)
3’10”Acid GER Acid Clearance
8”
volume clearance
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pH
MII-pH monitoring (non-acid)
pH 4
10sec
Z1
Z2
Z3
Z4
Z5
9” volume clearance
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Wenzl TG, et al. J Pediatr Gastroenterol Nutr 2012
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Wenzl TG, et al. J Pediatr Gastroenterol Nutr 2012
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Advantages of MII-pH monitoring Be superior to pH-study alone for
evaluation of GER-related symptom association
Picking up acid, non-acid or weakly acid reflux,
the direction of reflux To distinguish between liquid, solid and
gas reflux in all age groups
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Limitations of MII-pH study High cost Limited availability Limited therapeutic implications (clinical
relevance of measuring non-acidic reflux remains doubtful)
The lack of evidence-based parameters for assessment of GER
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High resolution manometry (HRM) Conventional manometry assemblies detect
pressure using a catheter with several water-perfused sideholes by gaps between the pressure sensors which are several centimeters long.
HRM catheters are equipped with intraluminal pressure transducers
Simultaneously measure from hypopharynx to stomach
Assign color to specific pressure levels which are than presented in a spatiotemporal plot
Pressure topography plots are more intuitive and easier learned by clinicians
Kessing BF, et al. Curr Gastroenterol Rep 2012
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Esophageal HRM and manometry
水平为时间轴,左纵轴压力色彩带(颜色越暖,压力越高),右纵轴为食管位置),TZ为移行区
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achalasia
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Clinical application of HRM HRM is superior to other diagnostic tools
for the evaluation of achalasia and contributes to a more specific classification of esophageal disorders in patients with non-obstructive dysphagia
Kessing BF, et al. Curr Gastroenterol Rep 2012
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Endoscopy Upper gastrointestinal endoscopy is the best
method of detecting esophagitis as a consequence of GERD.
Normal endoscopy (found in 60%-80% cases of GERD in children) does not rule out GERD and this type of GERD is called Non-erosive reflux disease (NERD).
Endoscopy needs to be combined with a biopsy to increase the diagnostic yield (especially in NERD) and to rule out other causes of esophagitis (like eosinophilic esophagitis, Crohn’s disease).
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Indications of endoscopy Persistence of symptoms despite therapy Dysphagia or odynophagia Evidence of GI bleeding or iron deficiency
anemia Stricture or ulcer on barium study Long duration GERD to detect Barrett’s
esophagus.
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Advantages of endoscopy Gives a direct information about the
presence and severity of esophagitis Detects complications like ulcer, stricture,
Barrett’s esophagus Documents healing of erosive esophagitis
after therapy. Exclude other causes of esophagitis by
endoscopic esophageal biopsy.
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Los Angeles classification A One or more mucosal breaks, each ≤ 5
mm in length B At least one mucosal break > 5 mm
long, but not continuous between the tops of adjacent mucosal folds
C At least one mucosal break that is continuous between the tops of adjacent mucosal folds, but which is not circumferential (< 75% of luminal circumference)
D Mucosal break that involves at least 75% of the luminal circumference
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Kamal A, et al. Best Practice Res Clin Gastroenterol 2010
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The evidence of histology Histology is more sensitive than
endoscopy in the early stage (non-erosive stage).
Erosive esophagitis is the most definite evidence of GERD on endoscopy.
Biopsy (2 cm proximal to gastroesophageal junction) helps to establish the diagnosis of GERD if there is no erosion or mucosal break on endoscopy.
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Esophageal histological features of GERD Basal zone hyperplasia (>20% of total thickness) Elongation of papillae (>50% of total thickness) Infiltration with neutrophils or eosinophils
(<15/high power field) The presence of dilated intercellular spaces Growing of blood vessels in papilla
Histological changes are neither sensitive nor specific for reflux disease in NERD cases and should not be used alone to diagnose or exclude GERD Poddar U. Indian Pediatr 2013
Tobey NA, et al. Gastroenterology 1996Boccia G, et al. Am J Gastroenterol 2007Vandenplas Y, et al. J Pediatr Gastroenterol Nutr 2009
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Barium UGI series Be useful to detect anatomical anomalies
such as the angle of His, esophageal dysmotility, mucosal irregularity, stricture, and hiatus hernia, but not useful in diagnosing GERD.
The sensitivity and specificity to diagnose GERD is less than 50%.
Cannot differentiate physiological from pathological reflux.
Most useful in ruling out underlying obstruction such as that due to achalasia
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Nuclear scintigraphy Be a non-invasive test but has poor
sensitivity and specificity. To confirm silent aspiration in patients
with recurrent pneumonia due to aspiration of gastric contents.
Be a useful tool in evaluation of delayed gastric emptying
Not recommended for the routine evaluation of pediatric patients with suspected GERD.
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Infant GER questionnaire (I-GERQ)
Orenstein SR, et al. Clin Pediatr 1996
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I-GERQ Maximum total score:25 Score>7, for diagnosing GERD in infants
Sensitivity 74% Specificity 94%
Can be used to segregate those infants who needs empirical therapy or further investigation because of its simplicity (take just 20 minutes to complete) and reproducibility.
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Rome III criteria Must include all of the following in
otherwise healthy infants 3 weeks to 12 months of age
Regurgitation 2 or more times per day for 3 or more weeks
No retching, hematemesis, aspiration, apnea, failure to thrive, feeding or swallowing difficulties, or abnormal posturing
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Diagnostic test When symptoms are not classical and in cases
with complicated GERD Endoscopy,pH study, barium upper GI series
In a patient with classical symptoms of GERD No need to confirm the presence of GER by pH study or
by endoscopy In patients with extra-esophageal symptoms like
respiratory symptoms without any GER symptoms pH study is required to document reflux
When esophagitis is suspected (pain or blood loss) Upper gastrointestinal endoscopy with esophageal
biopsy is recommended Any suggestion of an anatomical abnormality like
intestinal obstruction or dysphagia Barium upper GI series is indicated
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Diagnostic approach to GERD There is no gold standard for the diagnosis
of GERD. The choice of investigation depends on the
clinical situation for which the investigation is asked for.
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Diagnostic criteria of pathological GER RI is the main parameter in diagnosing GERD. RI 10%(<1 year), 5% (>1 year ) RI 10%(<1 year), 4.2%(>1 year) USA: RI≥12% (<1 year),≥6% (>1 year) RI>7% as abnormal, <3% as normal, 3-7% as
indeterminate (ESPGHN, NASPGHN) Boix-Ochoa score >11.99 Demeester score >14.72
Van der Pol RJ, et al. J Pediatrics 2012Vandenplas Y, et al. J Pediatr Gastroenterol Nutr 2009Mattioli G, et al. Dig Dis Sci 2006Aggarwal S, et al.Trop Gastroenterol 2004Wenzl TG. J Pediatr Gastroenterol Nutr 2011
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Management---GER in infants Counseling-the most important part
Explain the natural history of GER in infants to parents or care-givers
Other measures Feeding advice
Avoid overfeeding, forceful feeding Try to give small but frequent feeds
positioning Prone position-not recommended (the risk of SIDS) Left lateral position (age>13m)-the best in preventing
reflux feed thickening
Adding rice, corn or potato starch decrease the number regurgitation of vomiting does not decreases the acid exposure of esophagus
Feed thickener has only cosmetic value but no therapeutic benefit.
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PPIs PPIs are not recommended in this subset
of patient Only a few of the infants are likely to have
acid-related cause for their symptoms The largest randomized, controlled trial in
infants showed that for symptoms, presumably to be related to reflux disease, a PPI was not better than placebo.
Orenstein SR, et al. J Pediatr 2009
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Management---GERD in children Besides medication, life-style modification
in terms of weight reduction, avoiding caffeine, chocolate, abstinence from alcohol, tobacco helps in children.
Adolescents, like in adults, may benefit from the left lateral decubitus sleeping position with head-end elevation
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Pharmacological therapy Acid suppressants
Histamin-2 receptor antagonists (H2RA) Ranitidine: 6-8mg/kg/day, bid or tid Famotidine:1mg/kg/day, bid
Proton pump inhibitors (PPIs) Omeprazole:0.7 to 3.5 mg/kg/day, qd
Neutralizing or surface protective agents (antacids or sucralfate)
Prokinetics
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H2RA Rapid onset of action (in 30 min) Short acting (6 hr) acid suppressants used for on-demand therapy (SOS therapy) A lack of post-prandial acid suppressant
effect Develop tachyphylaxis on long-term use
(in 6 weeks) Cannot be used for long term therapy H2RA are less effective than PPI
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PPIs Inhibit acid secretion by irreversibly
blocking Na+-K+-ATPase in the apical membrane of parietal cells
Be taken 30 min before breakfast as parietal cells get activated in response to a meal.
Require a higher per kilogram dose than adults to obtain a similar degree of acid suppression due to higher metabolism of the drug. Omeprazole, 2-2.5mg/kg/day Lansoprazole, 1.4mg/kg/day
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The advantages of PPIs More effective in relieving symptoms and healing
esophagitis than any other acid suppressants Prolonged action (requires once daily dose) No tachyphylaxis on prolonged use Relatively safe drug on long term use Facilitate gastric emptying due to decrease 24 hr
gastric secretion volumes No role of PPIs in on-demand therapy, as it takes
2-8 days for them to have maximum effect. FDA approved for pediatric use out of all
omeprazole, lansoprazole and esomeprazole
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Side effect of PPIs Mild side effects have been reported in up
to 14% of children Most common side effects
headache diarrhea constipation nausea
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Prokinetics metoclopramide, domperidone,
erythromycin, baclofen or itopride in the management of GERD
prokinetics may be of some use is GERD with associated gastroparesis
Vandenplas Y, et al. J Pediatr Gastroenterol Nutr 2009Poddar U. Indian Pediatr 2013
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Duration of medical therapy GERD needs profound acid suppression for a
longer duration of time PPI therapy is recommended for at least 12
weeks and then to taper over 2 to 3 months as rebound hyperacidity after sudden stoppage of PPI
No symptomatic improvement in 4 weeks then the dose of PPI needs to be increased
A relapse on withdrawal of PPI, medication needs to be restarted
Frequent relapses or continuous symptoms are indications for prolonged PPI therapy or surgery
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Repeat endoscopy to document healing is indicated at the end of 12 weeks course in erosive esophagitis
Prolonged PPI therapy (median 3 years and up to 12 years) is safe
Full healing dose is superior to half dose in PPI maintenance therapy
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Surgery Nissen fundoplication (open or laparoscopic) may
be of benefit in children with confirmed GERD Who have failed optimal medical therapy Who are dependent on medical therapy for a long time Who are significantly noncompliant to medical therapy Who have life threatening complication of GERD
Point: who need surgery most, develop surgery related complications and surgical failure most
Fundoplication in early infancy has a higher failure rate than in late childhood
Hassall E. Arch Dis Child 2005Vandenplas Y, et al. J Pediatr Gastroenterol Nutr 2009Poddar U. Indian Pediatr 2013
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Conclusion GER is common in infants but GERD is not so common in
early childhood Most infants have physiological reflux and need minimal
intervention as their symptoms resolve by 18 months of age
There is no gold standard diagnostic test for GERD and investigation should be tailored to the clinical concern for a given child For extraesophageal manifestations, pH-metry with or without
impedance is the best investigations For esophagitis, endoscopy is the best investigations
Empirical PPI therapy for 4 weeks is justified in older children and adolescents with classical symptoms
Medical therapy with PPI is very effective and safe. Surgical therapy is not a panacea as it carries significant
morbidity and often fails in those who need it most.
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