gastroesophageal reflux in children - zhejiang...

Gastroesophageal reflux in children

浙江大学医学院附属儿童医院

江米足

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

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

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

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

Anti-reflux mechanism

Liu XL, et al. Hong Kong Med J 2012

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


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


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

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.

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

Yuksel ES, et al. Eur J Med Sci 2010

Laryngeal findings in reflux laryngitis

Kamal A, et al. Best Practice Res Clin Gastroenterol 2010

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

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

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

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

24 hr ambularoty pH-metry

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

Esophageal pH monitoring Advantages

Be done in any age Be relatively non-invasive

Disadvantage Does not measure non-acid or weakly acidic

reflux

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

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

van Wijk MP, et al. J Pediatr Gastroenterol Nutr 2009

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

pH

MII-pH monitoring (non-acid)

pH 4

10sec

Z1

Z2

Z3

Z4

Z5

9” volume clearance

Wenzl TG, et al. J Pediatr Gastroenterol Nutr 2012

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

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

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

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

achalasia

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

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).

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.

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.

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

Kamal A, et al. Best Practice Res Clin Gastroenterol 2010

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.

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

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

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.

Infant GER questionnaire (I-GERQ)

Orenstein SR, et al. Clin Pediatr 1996

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.

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

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

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.

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

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.

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

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

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

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

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

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

Side effect of PPIs Mild side effects have been reported in up

to 14% of children Most common side effects

headache diarrhea constipation nausea

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

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

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

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

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.