Gastro-oesophageal

reflux disease

The right clinical information, right where it's needed

Last updated: May 29, 2018

 Table of Contents
Summary 3

Basics 4
Definition 4
Epidemiology 4
Aetiology 4
Pathophysiology 4
Classification 5

Prevention 6

Diagnosis 7
Case history 7
Step-by-step diagnostic approach 7
Risk factors 8
History & examination factors 9
Diagnostic tests 10
Differential diagnosis 13
Diagnostic criteria 15

Treatment 16
Step-by-step treatment approach 16
Treatment details overview 18
Treatment options 19
Emerging 24

Follow up 25
Recommendations 25
Complications 25
Prognosis 26

Guidelines 27
Diagnostic guidelines 27
Treatment guidelines 28

Evidence scores 31

References 33

Images 40

Disclaimer 42
 Summary

◊ Diagnosis is clinical. A therapeutic trial of a proton-pump inhibitor (PPI) can serve for both diagnosis
and initial treatment.

◊ Upper endoscopy is indicated to evaluate for complications; for atypical, persistent, or relapsing
symptoms; or for alarm features (e.g., weight loss, anaemia).

◊ High rate of relapse upon stopping treatment.

◊ Serious complications include stricture, Barrett's oesophagus, or oesophageal carcinoma.

 Gastro-oesophageal reflux disease Basics

Definition
The American College of Gastroenterology defines GORD as 'symptoms or complications resulting from the
reflux of gastric contents into the [o]esophagus or beyond, into the oral cavity (including larynx) or lung'.[1]
BASICS

Typical symptoms are heartburn and acid regurgitation. Atypical symptoms include cough, laryngitis, asthma,
or dental erosion. GORD may occur with or without oesophageal inflammation (oesophagitis). Symptoms
may be without erosions on endoscopic examination (non-erosive reflux disease or NERD), or with erosions
present (ERD).[1]

The American Gastroenterological Association's definition of GORD follows the Montreal criteria.[2] [3] The
requirement is reflux of stomach contents causing troubling symptoms that affect wellbeing or that cause
complications.

Epidemiology
This is a common condition that affects between 10% and 20% of people in western countries.[2] There is
global variation, with less than 10% prevalence in Asia.[8] All age groups are affected.

There is no evidence for clear predictive factors. Obesity is considered a risk factor for GORD.[9] [10] The
risk may be related to increasing BMI. In one meta-analysis, the relative risk for symptoms was 1.43 for
BMI 25 to 30 kg/m^2 and 1.94 for BMI >30 kg/m^2.[11] Twin studies suggest that a genetic component may
exist.[12] Alcohol use, smoking, and intake of specific foods (such as coffee, mints, citrus fruits, or fats)
may predispose to, or trigger, GORD, but the evidence is not clear. Drugs that reduce lower oesophageal
sphincter pressure (e.g., calcium channel blockers) may promote GORD.[13]

Aetiology
The lower oesophageal sphincter regulates food passage from the oesophagus to the stomach and contains
both intrinsic smooth muscle and skeletal muscle. Episodes of transient lower oesophageal sphincter
relaxation are a normal phenomenon, but they occur more frequently in GORD, causing reflux of gastric
contents into the oesophagus. Transient lower oesophageal sphincter relaxation is more common after meals
and is stimulated by fat in the duodenum.[3] It is more likely to occur if there is a hiatal sac containing acid.
Patients with severe reflux often have a hiatus hernia and decreased resting lower oesophageal sphincter
pressure. However, pressure can be high in mild to moderate reflux.[14]

Pathophysiology
The severity of mucosal damage depends on the duration of contact with gastric contents, characteristics
of the gastric contents (acid, pepsin, and bile salts are damaging to the mucosa), and resistance of the
epithelium to damage.

The duration of contact with gastric contents depends on the number of episodes of reflux, the efficacy of
oesophageal peristalsis, and the neutralisation of acid by saliva.[3] Low-amplitude oesophageal contractions
can occur in severe reflux, reducing the ability to clear acid from the oesophagus.

Laryngo-pharyngeal symptoms may be caused by intermittent pharyngeal reflux. This occurs mostly at
night, when the upper oesophageal sphincter resting tone is reduced. Vagal stimulation (caused by acid

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Gastro-oesophageal reflux disease Basics
in the lower oesophagus) may cause chronic coughing and throat clearing. Definitive evidence for these
mechanisms is lacking.[15] [16]

Reflux-induced asthma may be caused by chronic aspiration of reflux contents and vasovagal

BASICS
bronchoconstriction, but a clear causal relation has not yet been established. Asymptomatic gastro-
oesophageal reflux is common among patients with poorly controlled asthma, but treatment with proton-
pump inhibitors has not been shown to improve asthma control.[17] Aspiration pneumonia may be caused by
oesophageal motor dysfunction, but its prevalence is unknown.[16]

The reasons are not clear for symptoms such as heartburn, regurgitation, or dysphagia that persist despite
therapy with proton-pump inhibitors and remain unexplained by endoscopy, manometry, or acid monitoring.
Possibilities include hypersensitivity or functional syndromes, but there is a lack of evidence.[3]

Classification
Montreal definition[2]
This classifies oesophageal syndromes.

1. Syndromes with symptoms and no injury:

• Typical reflux syndrome

• Reflux chest pain syndrome.
2. Syndromes with oesophageal injury:

• Reflux oesophagitis
• Reflux stricture
• Barrett's oesophagus
• Oesophageal adenocarcinoma.

Extra-oesophageal syndromes

1. Established associations:

• Reflux cough syndrome

• Reflux laryngitis syndrome
• Reflux asthma syndrome
• Reflux dental erosion syndrome.
2. Proposed associations:

• Pharyngitis
• Sinusitis
• Idiopathic pulmonary fibrosis
• Recurrent otitis media.

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PREVENTION Gastro-oesophageal reflux disease Prevention

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Gastro-oesophageal reflux disease Diagnosis

Case history
Case history #1
A 42-year-old woman has heartburn after meals and a sour taste in her mouth. For the past 4 to 6 months
she has had symptoms several times per week. Symptoms are worse when she lies down or bends over.
Antacids help somewhat. The patient has no dysphagia, vomiting, abdominal pain, exertional symptoms,
melaena, or weight loss. Past medical history and family history are non-contributory. The patient drinks
alcohol occasionally and does not smoke. On physical examination, height is 1.63 m (5 feet 4 inches),
weight 77.1 kg, and BP 140/88 mmHg. The remainder of the examination is unremarkable.

Other presentations
Patients may have only nocturnal symptoms. Traditional alarm symptoms are anaemia, dysphagia,
haematemesis, melaena, persistent vomiting, and involuntary weight loss (>5% body weight),[4] which
raise the possibility of oesophagitis, peptic stricture, or cancer. Extra-oesophageal symptoms are
hoarseness (acid laryngitis), persistent non-productive cough, pressure deep in the throat, and throat
clearing. Extra-oesophageal manifestations include asthma, bronchitis, chest pain, oral disease, sinusitis,
and recurrent pneumonia.[5] [6] In patients with GORD-associated asthma, there may be a negative
family history; adult onset; wheezing exacerbated by exercise, meals, or supine position; nocturnal
wheezing or cough; or reflux symptoms preceding asthma symptoms.[7]

Step-by-step diagnostic approach

Diagnosis is clinical, supported by testing when required. Heartburn and regurgitation are the most reliable
symptoms.[1] These often occur after meals, especially large or fatty meals. Symptoms may be worse when
the patient is lying down or bending over. Relief with antacids is typical. Atypical symptoms include cough,
laryngitis, asthma, or dental erosion. Alarm symptoms (anaemia, dysphagia, haematemesis, melaena,

DIAGNOSIS
persistent vomiting, or involuntary weight loss) raise the possibility of oesophagitis, peptic stricture, or cancer.
Physical examination is generally normal.

While typical patients may be given a therapeutic trial of proton-pump inhibitors (PPIs), those with long-
standing or alarm symptoms warrant additional investigation. Those who do not respond to PPIs also merit
further evaluation for complications or other conditions.

Typical symptoms
A short trial (8 weeks) of PPIs and lifestyle therapy (such as weight loss if needed, and elevation of head
of bed for nocturnal features) should be started in patients with typical symptoms.[1] Symptom relief
is presumed to be diagnostic, but failure to relieve does not exclude GORD. Using ambulatory pH as
a reference standard, a short trial of high-dose PPI has a sensitivity of 78%, but the specificity is only
54%.[1]

Longstanding, unresponsive, or atypical symptoms

Upper endoscopy (oesophagogastroduodenoscopy, OGD) is indicated in patients with atypical, relapsing,
or persistent symptoms.[24] Barrett's oesophagus may be found after healing of higher grades of erosive

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 Gastro-oesophageal reflux disease Diagnosis
oesophagitis. Thus, if endoscopy is performed to diagnose GORD, it may best be performed off therapy. If
performed because of concern for Barrett's oesophagus (e.g., long-standing symptoms), it may be best to
carry out the procedure during treatment. Unsedated surgery-based transnasal upper endoscopy has also
been proposed as a screening tool,[25] but it is not the standard endoscopic approach.

Alarm signs and symptoms that suggest complicated disease include weight loss, dysphagia,
odynophagia, or evidence of blood in stool. These patients warrant endoscopy. Endoscopy is also
indicated for atypical features such as laryngitis, globus, tooth enamel erosion, or halitosis.
[Fig-1]

Barium imaging is rarely used in the evaluation of GORD, as endoscopy provides direct visualisation and
the opportunity for biopsy. However, barium swallow may be useful in patients with dysphagia for whom
endoscopy is contraindicated or unavailable, or as a complement to endoscopy.

Patients with persistent symptoms on therapy with PPIs and unrevealing endoscopy undergo further
testing, but guidelines differ as to the sequence. American Gastroenterological Association 2008
guidelines recommend manometry next, to evaluate oesophageal contractions and lower oesophageal
sphincter function. American College of Gastroenterology 2013 guidelines recommend ambulatory
reflux (pH or impedance-pH) monitoring next, with manometry only advised preoperatively.[1] American
Gastroenterological Association 2008 guidelines recommend either pH or impedance-pH testing as the
next step (done off therapy for 7 days) if manometry is normal.[3] [26] Ambulatory pH monitoring identifies
patients whose symptoms correlate with oesophageal acid; impedance-pH testing may be used to detect
both acid and non-acid reflux events. However, outcome studies evaluating usefulness are needed for
impedance-pH testing in investigation of refractory reflux symptoms.[27] [28]

Oesophageal capsule endoscopy was introduced as a less-invasive, safe alternative to upper endoscopy,
and a potential screening and diagnostic tool to evaluate oesophageal pathology. Studies have shown
only moderate sensitivity and specificity for diagnosis of oesophageal disorders, and it has a limited role
and acceptance in screening for mucosal disease (erosive oesophagitis and Barrett's oesophagus).[29]
[30] [31] Capsule endoscopy is done for patient convenience in select circumstances. It is contraindicated
in the presence of suspected (e.g., presence of dysphagia) or known stricture or adhesions.
DIAGNOSIS

Routine testing for Helicobacter pylori is not recommended by guidelines.

Risk factors
Strong
FHx of heartburn or GORD
• Immediate family history of heartburn or GORD: approximately 3 times more likely to have
symptoms.[18]
• GORD is more common in monozygotic than dizygotic twins.[16]

older age
• Risk of GORD increases with age.[19]

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Gastro-oesophageal reflux disease Diagnosis
hiatus hernia
• Anatomical changes associated with hiatus hernia may facilitate reflux by reducing competence of the
gastro-oesophageal junction as well as by inhibiting clearance of oesophageal acid post-reflux.

obesity
• Considered a risk factor for GORD.[9] [10] Relative risks for symptoms of GORD were 1.43 for a BMI
25 to 30 kg/m^2 and 1.94 for a BMI >30 kg/m^2 in one meta-analysis.[11]

Weak
lower oesophageal sphincter (LOS) tone-reducing drugs
• Smooth muscle relaxants and anticholinergics reduce LOS tone through direct smooth muscle and
neural mechanisms, facilitating reflux of stomach contents. Such drugs include nitrates, calcium
channel blockers, alpha- and beta-adrenergic agonists, theophylline, and anticholinergics.

psychological stress
• A higher score on a psychosomatic symptom checklist has been associated with a higher risk of
having symptoms.[18]

asthma
• Identified as a risk factor in Georgia Medicaid study.[20]
• However, while asymptomatic gastro-oesophageal reflux is common among patients with poorly
controlled asthma, treatment with proton-pump inhibitors has not been shown to improve asthma
control.[17]

NSAIDs
• May contribute to oesophagitis and strictures in patients with GORD. Evidence unclear as to whether
NSAIDs cause GORD.[21]

smoking

DIAGNOSIS
• Past history of smoking associated with an odds ratio of 1.6 for symptoms.[18] [22]

alcohol consumption
• Evidence is mixed. Some studies suggest that having >7 drinks weekly may be associated with an
odds ratio of 1.9 for having symptoms.[18]

dietary factors
• Candidates include caffeinated foods or drinks, carbonated drinks, chocolate, citrus, and spicy foods.
• Evidence is limited. A Swedish study found no association with any of the above or with size of food
portion.[23]

History & examination factors

Key diagnostic factors
presence of risk factors (common)
• Strong risk factors include family history of heartburn or GORD; obesity; older age; or hiatus hernia.

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 Gastro-oesophageal reflux disease Diagnosis
heartburn (common)
• Burning sensation in the chest after meals is typical.
• Can be worse after the patient has been lying down or bending over.
• Can occur at night but is not usually exertional.

acid regurgitation (common)

• Reflux of acid into the mouth, with a sour or bitter taste, mainly after meals.

Other diagnostic factors

dysphagia (uncommon)
• Causes of dysphagia such as a motility disorder, stricture, ring, or malignancy should be excluded,[1]
especially if progressive.

bloating/early satiety (uncommon)

• Other causes should be ruled out (e.g., cancer or stricture).

laryngitis (uncommon)
• Association with GORD based on population-based studies. However, extra-oesophageal syndromes
are non-specific and usually multi-factorial in origin.[3]
• ENT referral may be required, but positive laryngoscopy findings alone do not establish a causal
connection to GORD.[1]

globus (uncommon)
• Patients may describe a lump in the throat that is present despite swallowing.[1]

enamel erosion (uncommon)

• Reflux of acid may cause enamel erosion of teeth.

halitosis (uncommon)
DIAGNOSIS

• Has been found to be more common in people with GORD.[32] Patient may not be aware.

Diagnostic tests
1st test to order

Test Result
proton-pump inhibitor (PPI) trial symptom improvement
• Further tests are indicated if symptoms do not improve with
therapeutic 8-week trial of a PPI or if patient has alarm symptoms.[1]

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Gastro-oesophageal reflux disease Diagnosis

Other tests to consider

Test Result
oesophagogastroduodenoscopy (OGD) may show oesophagitis
(erosion, ulcerations,
• Indicated for alarm symptoms or symptoms suggesting complicated
strictures) or Barret t's
disease (atypical, persistent, or relapsing symptoms).[1]
oesophagus
[Fig-1]
• Normal findings on endoscopy can occur with GORD (i.e., non-
erosive reflux disease [NERD]).[1] Routine biopsies are not
recommended by guidelines.[1] [24]
• Evidence is conflicting as to whether frequency and severity of
symptoms can predict Barrett's oesophagus, severity of oesophagitis,
or other complications.
• Higher grades of erosive oesophagitis may be associated with the
finding of Barrett's oesophagus with healing. Thus, if endoscopy is
performed to diagnose GORD, it may best be performed off therapy.
If performed because of concern for Barrett's oesophagus (e.g., long-
standing symptoms), it may be best to carry out the procedure during
treatment.
• Unsedated surgery-based transnasal upper endoscopy has also
been proposed as a screening tool,[25] but it is not the standard
endoscopic approach.
ambulatory pH monitoring pH <4 more than 4% of the
time is abnormal
• Patients with persistent symptoms on therapy with twice-daily PPIs
and unrevealing endoscopy undergo further testing, but guidelines
differ as to the sequence. American Gastroenterological Association
2008 guidelines recommend manometry next.[3] American College
of Gastroenterology 2013 guidelines recommend ambulatory pH
or impedance-pH monitoring next, with manometry only advised
preoperatively.[1]
• Ambulatory pH monitoring can demonstrate abnormal exposure to
oesophageal acid in the absence of oesophagitis.[33]
• There are 2 types of pH monitoring: naso-oesophageal catheter and
wireless radiotelemetry capsule monitoring. Wireless radiotelemetry

DIAGNOSIS
method allows monitoring for 48 hours without a naso-oesophageal
catheter, which results in less discomfort and fewer interruptions of
daily activities.
• Controversial whether to perform this testing while on or off
proton-pump inhibitor (PPI) therapy. American Gastroenterological
Association guidelines (2008) recommend doing impedance-pH
testing or ambulatory pH monitoring while off PPI therapy for 7
days.[3] Either ambulatory pH or impedance-pH was recommended
to evaluate patients with a suspected oesophageal GORD syndrome
who have not responded to an empirical trial of PPI therapy, have
normal findings on endoscopy, and have no major motor abnormality
on manometry. American College of Gastroenterology guidelines
(2013) also recommend that impedance-pH monitoring can be done
on medication to measure non-acid reflux.[1]

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 Gastro-oesophageal reflux disease Diagnosis

Test Result
oesophageal manometry may suggest achalasia,
oesophageal spasm, or
• Patients with persistent symptoms on therapy with twice-daily PPIs
other motor disorders
and unrevealing endoscopy undergo further testing, but guidelines
differ as to the sequence. American Gastroenterological Association
2008 guidelines recommend manometry as a next step.[3] American
College of Gastroenterology 2013 guidelines recommend ambulatory
pH monitoring next, with manometry only advised preoperatively.[1]
• Manometry evaluates oesophageal contractions and lower
oesophageal sphincter function and may detect subtle presentations
of oesophageal motility disorders such as achalasia or diffuse
oesophageal spasm.
combined impedance-pH testing may detect acid or non-
• Can quantify exposure to oesophageal acid and identify reflux events acid reflux events
regardless of acidic content to assess correlation with symptoms.[3]
[26]
• Oesophageal impedance testing detects the occurrence of changes
in the resistance to electrical current across adjacent electrodes
positioned on a catheter. It can detect antegrade and retrograde bolus
transit of liquid and gas. Impedance monitoring cannot detect either
the acid content or volume of the intraluminal contents. Therefore, a
pH probe is usually incorporated into the assembly. Impedance-pH
monitoring can thus detect acid as well as non-acid reflux.
• Combined pH monitoring with oesophageal impedance may be useful
in the evaluation of endoscopy-negative patients with complaints
of heartburn or regurgitation despite proton-pump inhibitor (PPI)
therapy.[34] Controversial whether to perform this testing while on or
off PPI therapy. American Gastroenterological Association guidelines
(2008) recommend doing impedance-pH testing or ambulatory pH
monitoring while off PPI therapy for 7 days.[3] Either ambulatory
pH or impedance-pH was recommended to evaluate patients with a
suspected oesophageal GORD syndrome who have not responded to
an empirical trial of PPI therapy, have normal findings on endoscopy,
and have no major motor abnormality on manometry. American
DIAGNOSIS

College of Gastroenterology guidelines (2013) also recommend that

impedance-pH monitoring can be done on medication to measure
non-acid reflux.[1]
• However, outcome studies evaluating usefulness are needed
for impedance-pH testing in investigation of refractory reflux
symptoms.[27]
barium swallow may exclude other causes
of dysphagia
• Can be helpful in the diagnosis and evaluation of esophagitis.[35]
However, a barium swallow is more useful for patients presenting with
dysphagia; not a screening test for GORD.[1] May be complementary
to endoscopy for dysphagia.
• The mucosa may look nodular or granular. Overall sensitivity is low
for detecting signs of oesophagitis.[1]

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Gastro-oesophageal reflux disease Diagnosis

Test Result
oesophageal capsule endoscopy may show oesophagitis or
Barret t's oesophagus
• Involves swallowing a capsule endoscope to visualise the
oesophagus without the need for sedation.
• Was introduced as a less-invasive, safe alternative to upper
endoscopy, and a potential screening and diagnostic tool to evaluate
oesophageal pathology. Studies have shown only moderate
sensitivity and specificity for diagnosis of oesophageal disorders,
and it has a limited role and acceptance in screening for mucosal
disease (erosive oesophagitis and Barrett's oesophagus).[29] [30]
[31] Capsule endoscopy is done for patient convenience in selected
circumstances. It is contraindicated in the presence of suspected
(e.g., presence of dysphagia) or known stricture or adhesions.

Differential diagnosis

Condition Differentiating signs / Differentiating tests

symptoms
CAD • Cardiac aetiology must be • ECG may show ST changes
ruled out before considering or Q waves.
a diagnosis of GORD in • Exercise stress testing may
people with chest pain.[1] abnormal.
• Cardiac chest pain is
typically substernal,
precipitated by exertion, and
relieved by rest.

Functional oesophageal • No reliable differentiating • Functional heartburn

disorder/functional signs or symptoms. denotes endoscopy-negative
heartburn heartburn by definition. A
normal oesophageal pH
study differentiates between

DIAGNOSIS
non-erosive GORD and
functional heartburn. An
alternative is a normal
impedance-pH study. These
studies would usually be
done in patients who fail
to respond to proton-pump
inhibitor (PPI) therapy.

Achalasia • Dysphagia is typically • Oesophageal manometry

prominent. and/or oesophagram are
abnormal and consistent with
achalasia.

Non-ulcer dyspepsia • At least 3 months of • No definitive differentiating

recurrent upper abdominal tests. Oesophagitis is absent
pain, bloating, and nausea, on endoscopy for both non-
with no obvious structural erosive GORD and non-ulcer
cause.[36] dyspepsia, while peptic ulcer
disease was excluded.

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 Gastro-oesophageal reflux disease Diagnosis

Condition Differentiating signs / Differentiating tests

symptoms
Peptic ulcer disease • Burning pain in the • Endoscopy demonstrates
epigastrium, which occurs ulcer.
hours after meals or with • Testing for Helicobacter
hunger. pylori infection is often
• The pain often wakes positive, although not
the patient at night and diagnostic.
is relieved by food and
antacids.

Eosinophilic oesophagitis • Features of GORD and • Endoscopy may show

eosinophilic oesophagitis oesophageal rings, linear
overlap. However, furrows, white plaques,
patients with eosinophilic exudates, absence of a
oesophagitis may have hiatus hernia, and a narrow-
younger age, symptoms of calibre oesophagus.[37] [38]
dysphagia, food impactions, • Maximum peripheral
or documented food eosinophil count may be
allergies.[37] [38] higher than typical for
GORD.[38]
• Eosinophil count may be
≥15 per high power field
in sampled oesophageal
tissue.[37]
• There may be eosinophil
degranulation in biopsy
specimens.[38]

Proton pump inhibitor- • Should be diagnosed when • Therapeutic response to a

responsive oesophageal patients have oesophageal PPI. It is recommended that
eosinophilia symptoms and histological doses of PPI should be at
findings of oesophageal least similar to treat GORD-
eosinophilia, but related erosive oesophagitis
demonstrate symptomatic with a duration of 8 weeks
DIAGNOSIS

and histological response to continuing until the time of

proton-pump inhibition. a follow-up endoscopy and
• This entity is considered biopsy.
distinct from eosinophilic
oesophagitis,[39] but is not
necessarily a manifestation
of GORD.
• It is not known whether
patients with proton pump
inhibitor (PPI)-responsive
oesophageal eosinophilia
represent a GORD variant,
an eosinophilic oesophagitis
variant, or a separate
process.

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Gastro-oesophageal reflux disease Diagnosis

Condition Differentiating signs / Differentiating tests

symptoms
Malignancy • Suspected in older adults • Laboratory tests may show
presenting with alarm anaemia or abnormal LFTs.
symptoms: anaemia, acute • Tissue biopsies diagnostic.
or progressive dysphagia,
haematemesis, melaena,
persistent vomiting, or
involuntary weight loss.

Laryngopharyngeal reflux • Related to upper • Diagnosis is mainly clinical,

oesophageal sphincter no single test confirms it.
dysfunction allowing >4 • Laryngoscopy is useful to
events of acid reflux into the demonstrate varying degrees
laryngopharynx per day. of laryngeal oedema and
• Laryngeal symptoms include erythema.
dysphonia, cough, globus • Dual sensor pH probe
sensation, persistent throat is considered the gold
clearing, and/or dysphagia. standard for diagnosing
Less commonly, patients laryngopharyngeal reflux.
may exhibit vocal cord • Clinical response to
polyps or granulomas, empirical therapy with proton
laryngospasm, or subglottis pump inhibitors may be used
stenosis. as a diagnostic tool.[40]
• Only 35% to 40% of patients
experience heartburn;
oesophagitis is present in
25% of patients.

Diagnostic criteria
Los Angeles[4] [41] [42]

DIAGNOSIS
The Los Angeles classification of oesophagitis assigns patients to grades A to D, depending on endoscopic
findings of mucosal breaks in the distal oesophagus indicative of oesophagitis:

• Grade A: breaks of ≤5 mm
• Grade B: breaks >5 mm
• Grade C: breaks extending between the tops of ≥2 mucosal folds, but <75% of circumference
• Grade D: circumferential breaks (≥75%).

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 Gastro-oesophageal reflux disease Treatment

Step-by-step treatment approach

The main goals of treatment are to control symptoms and to prevent complications. The basis of treatment is
acid suppression.[1] Most patients with GORD require prolonged pharmacotherapy with acid suppressants.
Proton pump inhibitors are the most effective drugs in this category and are currently the mainstay therapy
for GORD. Several studies have highlighted risks associated with long-term use of these drugs; therefore,
attempts to stop or reduce the dose to the minimum necessary to maintain symptomatic control should
always be pursued.[43] Diagnostic manoeuvres such as endoscopy help to determine appropriate treatment.
Conversely, treatment with proton-pump inhibitors (PPIs) is often also diagnostic.

Management of mild and typical GORD

People with mild or infrequent cases of GORD often seek help after self-treatment. Patient-
directed treatments include antacids,1[C]Evidence H2 antagonists,2[B]Evidence and lifestyle
changes.3[C]Evidence Lifestyle changes are recommended for all patients, although evidence of
effectiveness is weak.[1] These include: weight loss for overweight people; smoking cessation for tobacco
smokers;[44] head-of-bed-elevation; and avoidance of late-night eating if nocturnal symptoms are
present.[1] [44] Routine food eliminations (e.g., chocolate, caffeine, alcohol, acidic and/or spicy foods) are
not required unless selective changes provide individual benefit.

PPIs plus lifestyle changes are usually the first-line treatment for people with GORD who seek
treatment.4[A]Evidence For patients <40 years old who have typical, regular heartburn and no alarm
symptoms, treatment should be started with standard-dose PPIs for about 8 weeks.[1] It is recommended
to start treatment with the lowest effective dose of PPI.[8] If there is absent or inadequate response,
treatment can proceed to high-dose PPIs and endoscopy. If it is not possible to use high-dose PPIs
(e.g., financial reasons), some patients respond to switching the PPI. If endoscopy fails to show
erosive oesophagitis or Barrett's oesophagus, further diagnostic testing should be considered. Patients
with refractory GORD should be referred to a gastroenterologist for diagnostic testing. Reasons for
refractoriness should be sought; for example: functional GORD/hypersensitivity (patient does not have
GORD by standard pH definition), non-adherence to treatment, non-acidic reflux, inadequate acid control,
or unusual circumstances such as Zollinger-Ellison syndrome or individuals with polymorphisms in
cytochrome P450 2C19 (CYP2C19) resulting in rapid metabolism of proton pump inhibitors.[45]

Bedtime adjunctive use of H2 antagonists may be considered in people with nocturnal symptoms or pH-
monitoring evidence of nocturnal oesophageal acid reflux, when PPIs are not completely effective.[1]
However, tachyphylaxis may occur.

Management of atypical and complicated symptoms

Patients who present with complicated or atypical GORD (e.g., dysphagia or evidence of GI bleeding)
usually have immediate endoscopy. Patients whose symptoms have lasted >5 years, or who are older
than 40 years, also usually have endoscopy. These patients should also be treated with PPIs but not
empirically.

Associated dysmotility
TREATMENT

The only promotility agent supported by evidence was cisapride, which is unavailable because of
concerns about serious dysrhythmias. The only available promotility agent, metoclopramide, has
no confirmed role in therapy of GORD and is associated with adverse events such as permanent

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Gastro-oesophageal reflux disease Treatment
extrapyramidal effects, movement disorders, and psychiatric sequelae. Therefore, promotility agents are
not recommended.

Duration of medical therapy

Patients who respond to therapy will often need long-term maintenance treatment with PPIs.5[A]Evidence

Maintenance PPI therapy is recommended for those who have symptoms when the PPI is discontinued,
as well as for those with erosive oesophagitis and Barrett's oesophagus.[1] Most patients relapse off PPI
therapy. However, there are risks associated with long-term use of these drugs; therefore, attempts to
stop or reduce the dose to the minimum necessary to maintain symptomatic control should always be
pursued.[43]

Some people with non-erosive reflux disease (NERD) may be able to use on-demand or intermittent PPI
therapy.[1] Some experts recommend a trial of step-down therapy,[46] [47] although it is not routine.

Surgical alternatives
Surgery (open6[C]Evidence or laparoscopic7[C]Evidence fundoplication) is reserved mainly for people
who have had a good response to PPIs but who do not wish to take long-term medical treatment (e.g.,
due to side effects or non-adherence[1]). Laparoscopic Nissen (total) versus Toupet (270º) or anterior
(180º) fundoplications result in equivalent control of GORD symptoms.[48] [49] Guidelines recommend
preoperative ambulatory pH monitoring if no evidence of erosive oesophagitis, and preoperative
manometry.[1] People who do not respond to PPIs will probably not respond to surgery. Post-surgical
complications occur in up to 20% of patients.[50]

Patients should be involved in the decision to initiate surgery, as evidence for surgery is conflicting. The
long-term effectiveness of antireflux surgery was evaluated in a large nationwide populational study from
Sweden, in which 2655 individuals were followed for a median of 5.6 years after laparoscopic surgery.
Reflux recurrence (defined as need for acid suppressants for >6 months or repeat antireflux surgery) was
reported in 17.7% of individuals. Risk factors for reflux recurrence included: female sex, older age, and
presence of comorbid conditions (measured by the Charlson comorbidity index).[51] The benefits must be
balanced against the risk of mortality and other adverse effects.[52]

Minimally invasive approaches for GORD have been proposed. Magnetic sphincter augmentation with
beads has been shown to have similar efficacy results to laparoscopic nissen fundoplication in some
trials.[53] [54] [55] Rigorous patient selection is important for this novel procedure and patients with hiatal
hernias less than 2 cm in size seem to benefit the most from this approach. Dysphagia is a possible side
effect after this procedure.[56]

Issues related to long-term therapy with proton-pump inhibitors

(PPIs)
Theoretical clinical sequelae of chronic acid inhibition are not considered a barrier to long-term therapy.[3]
[43] Epidemiological studies have linked acid suppression to an increased risk of bone fractures or, with
short-term use, community-acquired pneumonia.[57] [58] [59] There is no defined role for screening
TREATMENT

for possible adverse effects or for avoidance of acid suppression because of them.[3] [60] Some,[61]
[62] but not all,[63] [64] [65] studies have found evidence for decreased efficacy of clopidogrel and
possible adverse outcomes when clopidogrel was used in conjunction with PPIs.[66] Concomitant use
of clopidogrel and omeprazole is not recommended. Long-term use of PPIs has been associated with
hypomagnesaemia.[60] Use of PPIs is also a risk factor for Clostridium difficile -associated diarrhoea.[67]

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 Gastro-oesophageal reflux disease Treatment
One observational study suggested that PPIs can increase the risk of dementia in older patients;[68]
however, another study found no association.[69] Similar observational cohort studies noted an
association between PPI use and chronic kidney disease.[70] However, these data have not been verified
by prospective trials.

Treatment details overview

Consult your local pharmaceutical database for comprehensive drug information including contraindications,
drug interactions, and alternative dosing. ( see Disclaimer )

Acute ( summary )
initial presentation

1st standard-dose proton-pump inhibitor

plus lifestyle changes

Ongoing ( summary )
proton-pump inhibitor-responsive

1st continued standard-dose proton-pump

inhibitor

2nd surgery

incomplete response to proton-pump

inhibitor

1st high-dose proton-pump inhibitor + further

testing

with nocturnal adjunct H2 antagonist

component
TREATMENT

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Gastro-oesophageal reflux disease Treatment

Treatment options

Acute
initial presentation

1st standard-dose proton-pump inhibitor

Primary options

» omeprazole: 20 mg orally once daily

OR

» omeprazole/sodium bicarbonate: 20/1100

mg to 40/1100 mg (capsule) orally once daily;
or 20/1680 mg to 40/1680 mg (powder) orally
once daily

OR

» esomeprazole: 20-40 mg orally once daily

OR

» rabeprazole: 20 mg orally once daily

OR

» pantoprazole: 40 mg orally once daily

OR

» lansoprazole: 15-30 mg orally once daily

OR

» dexlansoprazole: 30-60 mg orally once

daily

» Provides the most rapid symptom relief and

healing in oesophagitis (about 70% to 80% of
patients).[1] 4[A]Evidence

» More effective for symptom relief than H2

antagonists.[1]

» Initial course is 8 weeks.[1] Most patients will

need ongoing therapy.
plus lifestyle changes
TREATMENT

» These include: weight loss for overweight

people; head-of-bed elevation; and avoidance
of late-night eating if nocturnal symptoms are
present.[1] [44]

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 Gastro-oesophageal reflux disease Treatment

Acute
» Specific food eliminations (e.g., chocolate,
caffeine, alcohol, acidic and/or spicy foods) are
not routinely required, unless individual tailoring
seems to be beneficial.[1]

» Evidence of effectiveness limited.[1]

3[C]Evidence

Ongoing
proton-pump inhibitor-responsive

1st continued standard-dose proton-pump

inhibitor
Primary options

» omeprazole: 20 mg orally once daily

OR

» omeprazole/sodium bicarbonate: 20/1100

mg to 40/1100 mg (capsule) orally once daily;
or 20/1680 mg to 40/1680 mg (powder) orally
once daily

OR

» esomeprazole: 20-40 mg orally once daily

OR

» rabeprazole: 20 mg orally once daily

OR

» pantoprazole: 40 mg orally once daily

OR

» lansoprazole: 15-30 mg orally once daily

OR

» dexlansoprazole: 30-60 mg orally once

daily

» Discontinuation of full-dose proton-pump

inhibitors (PPIs) is often followed by a relapse in
TREATMENT

symptoms.5[A]Evidence

» Maintenance PPI therapy is recommended

for those who have symptoms when the PPI is
discontinued, as well as for those with erosive

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Gastro-oesophageal reflux disease Treatment

Ongoing
oesophagitis and Barrett's oesophagus.[1] Most
people will relapse off PPI therapy.

» Some people with non-erosive reflux disease

(NERD) may be able to use on-demand or
intermittent PPI therapy.[1] Some experts
recommend a trial of step-down therapy,[46]
[47] although it is not routine.

» Lifestyle changes can be continued, if they

appear to be effective.8[C]Evidence

» Epidemiological studies have linked acid

suppression to an increased risk of bone
fractures or community-acquired pneumonia.[57]
[58] [59] There is no defined role for screening
for possible adverse effects or for avoidance
of acid suppression because of them.[3] [60]
Some,[61] [62] but not all,[63] [64] [65] studies
have found evidence for decreased efficacy
of clopidogrel and possible adverse outcomes
when clopidogrel was used in conjunction with
PPIs.[66] Concomitant use of clopidogrel and
omeprazole is not recommended.

» There are risks associated with long-term

use of PPIs; therefore, attempts to stop or
reduce the dose to the minimum necessary to
maintain symptomatic control should always be
pursued.[43] [60] Use of PPIs is a risk factor for
Clostridium difficile -associated diarrhoea.[67]
2nd surgery

» Surgery (open6[C]Evidence or
laparoscopic7[C]Evidence fundoplication)
is reserved mainly for people who have had
a good response to proton-pump inhibitors
(PPIs) but who do not wish to take long-term
medical treatment.[1] Laparoscopic Nissen
(total) versus Toupet (270º) or anterior (180º)
fundoplications result in equivalent control of
GORD symptoms.[48] [49] 

» Guidelines recommend preoperative

ambulatory pH monitoring if no evidence
of erosive oesophagitis, and preoperative
manometry.[1] [71] People who do not respond
to PPIs will probably not respond to surgery.
Post-surgical complications occur in up to 20%
of patients.[50] Patients should be involved in
the decision to initiate surgery, as evidence for
surgery is conflicting; the long-term effectiveness
TREATMENT

is unclear; and the benefits must be balanced

against the risk of mortality and other adverse
effects.

» Minimally invasive approaches for GORD

have been proposed. Magnetic sphincter

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 Gastro-oesophageal reflux disease Treatment

Ongoing
augmentation with beads has been shown to
have similar efficacy results to laparoscopic
nissen fundoplication in some trials.[53] [54]
[55] Rigorous patient selection is important for
this novel procedure and patients with hiatal
hernias less than 2 cm in size seem to benefit
the most from this approach. Dysphagia is a
possible side effect after this procedure.[56]
incomplete response to proton-pump
inhibitor

incomplete response to proton- 1st high-dose proton-pump inhibitor + further

pump inhibitor testing
Primary options

» omeprazole: 20 mg orally twice daily

OR

» esomeprazole: 40 mg orally twice daily

OR

» rabeprazole: 20 mg orally twice daily

OR

» pantoprazole: 40 mg orally twice daily

OR

» lansoprazole: 30 mg orally twice daily

OR

» dexlansoprazole: 60 mg orally once daily

» Dosing is usually twice-daily, before breakfast

and dinner.[1]

» Can use a 2- to 3-month trial, but randomised

controlled trials are lacking.[72]

» Reasons for refractoriness should be sought:

for example, functional GORD/hypersensitivity
(patient does not have GORD by standard
pH definition), non-adherence to treatment,
non-acidic reflux, inadequate acid control,
Zollinger-Ellison syndrome, or individuals with
TREATMENT

polymorphisms in cytochrome P450 2C19

(CYP2C19) resulting in rapid metabolism of
proton pump inhibitors.[45]

» Patients should be referred to a

gastroenterologist for diagnostic testing.

22 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: May 29, 2018.
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Gastro-oesophageal reflux disease Treatment

Ongoing
» Epidemiological studies have linked acid
suppression to an increased risk of bone
fractures or community-acquired pneumonia.[57]
[58] [59] There is no defined role for screening
for possible adverse effects or for avoidance
of acid suppression because of them.[3] [60]
Some,[61] [62] but not all,[63] [64] [65] studies
have found evidence for decreased efficacy
of clopidogrel and possible adverse outcomes
when clopidogrel was used in conjunction with
proton-pump inhibitors (PPIs).[66] Concomitant
use of clopidogrel and omeprazole is not
recommended. Long-term use of PPIs has been
associated with hypomagnesaemia.[60] Use
of PPIs is a risk factor for Clostridium difficile -
associated diarrhoea.[67]
with nocturnal adjunct H2 antagonist
component
Primary options

» ranitidine: consult specialist for guidance on

dose

OR

» famotidine: consult specialist for guidance

on dose

OR

» nizatidine: consult specialist for guidance

on dose

OR

» cimetidine: consult specialist for guidance

on dose

» When proton-pump inhibitors (PPIs) are

not completely effective, bedtime adjunctive
use of H2 antagonists may be considered
in people with nocturnal symptoms or pH-
monitoring evidence of nocturnal oesophageal
acid reflux.[1] However, tachyphylaxis may occur,
and few data guide dose. As-needed dosing may
be possible.[1]
TREATMENT

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 Gastro-oesophageal reflux disease Treatment

Emerging
Endoscopic therapy
A variety of procedures have been tried. Two procedures currently in use are endoscopic radiofrequency
ablation and transoral incisionless fundoplication (TIF).[24] Currently there is insufficient evidence to
recommend these procedures.[73] [74] [75] There are no definite indications, and there are concerns
about safety and efficacy, patient selection, and durability.[76] Some trials have demonstrated safety and
symptomatic improvement with TIF.[77] [78] [79] It has been suggested that endoscopic antireflux therapy be
considered for selected patients with uncomplicated GORD after careful discussion with the patient regarding
potential adverse effects, benefits, and other available therapeutic options.[24]

Bariatric surgery for people with obesity and GORD

Obese patients with GORD may meet bariatric surgical criteria and may be under consideration for bariatric
surgery as a therapy for obesity.[1] Patients with GORD and who are obese may benefit from a bariatric
procedure rather than from an antireflux procedure.[71] Indications according to BMI and the best procedure
to use are not established; however, roux-en-Y gastric bypass appears to result in better control of reflux
symptoms (up to 70%) compared with other bariatric surgical procedures.[80]
TREATMENT

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Gastro-oesophageal reflux disease Follow up

Recommendations
Monitoring

FOLLOW UP
Routine endoscopy to assess for disease progression in subjects with erosive or non-erosive GORD
is not recommended by the American Gastroenterological Association (AGA) 2008 guidelines or
the American College of Gastroenterology (ACG) 2013 guidelines.[1] [3] Endoscopic surveillance is
recommended by most guidelines for patients with Barrett's oesophagus. This is based on longitudinal
studies and expert opinion, however, and benefit has not been confirmed by randomised controlled
clinical trials. In patients with Barrett's oesophagus without dysplasia, after at least 2 endoscopic
examinations 1 year apart with no evidence of disease progression, surveillance intervals can probably
be extended to 3 years. Surveillance endoscopies should be performed while reflux symptoms are
controlled on proton-pump inhibitor (PPI) therapy in order to heal oesophagitis and reduce the likelihood
of interference by inflammation in interpretations of results.[3] [81] [82] [83]

Patient instructions
The majority of patients will not respond to lifestyle changes alone. However, a trial of lifestyle
modifications is warranted, especially for mild or intermittent GORD. Weight reduction (for overweight
patients) and elevation of the head of the bed (for nocturnal symptoms) may be useful.[1] Specific food
eliminations (e.g., chocolate, caffeine, alcohol, acidic and/or spicy foods) are not routinely required,
unless individuals find these helpful.[1] 3[C]Evidence

Complications

Complications Timeframe Likelihood

oesophageal ulcer, haemorrhage, or perforation variable low

Ulceration, haemorrhage, or rarely perforation may occur in people with GORD.[78]

oesophageal stricture variable low

Healing of oesophageal damage in GORD involves collagen deposition. Contraction of the distal
oesophagus occurs, causing stricture formation.

Often associated with dysphagia for solid food.[24]

When stricture, Barrett's metaplasia, or adenocarcinoma were absent in the setting of a healed mucosa at
initial endoscopy, the risk for development of stricture was about 1.9% at 7 years' follow-up.[3]

Barret t's oesophagus variable low

White men >50 years at highest risk; risk increases with positive smoking history or hiatus hernia.

When stricture, Barrett's metaplasia, or adenocarcinoma were absent in the setting of a healed mucosa
at initial endoscopy, the risk for development of Barrett's oesophagus was about 0% at 7 years' follow-
up.[3] However, about 6% of people upon healing of Los Angeles C or D oesophagitis develop Barrett's
oesophagus (or have unmasking of disease).

Evidence is conflicting as to whether frequency and severity of symptoms can predict Barrett's
oesophagus, severity of oesophagitis, or other complications.
[Fig-2]

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 Gastro-oesophageal reflux disease Follow up

Complications Timeframe Likelihood

adenocarcinoma of the oesophagus variable low
FOLLOW UP

A rare complication but the prognosis is poor.

When stricture, Barrett's metaplasia, or adenocarcinoma were absent in the setting of a healed mucosa
at initial endoscopy, the risk for development of adenocarcinoma was about 0.1% at 7 years' follow-up.[3]
The risk for adenocarcinoma rises to about 0.5% a year in the setting of Barrett's oesophagus.
[Fig-3]

Prognosis

Most patients respond to treatment with proton-pump inhibitors (PPIs). Maintenance PPI therapy is
recommended for those who have symptoms when the PPI is discontinued, as well as for those with erosive
oesophagitis and Barrett's oesophagus.[1] Most patients relapse off PPI therapy. However, there are risks
associated with long-term use of these drugs; therefore, attempts to stop or reduce the dose to the minimum
necessary to maintain symptomatic control should always be pursued.[43]

Oesophageal adenocarcinoma may be a serious though rare complication of GORD. When stricture,
Barrett's metaplasia, or adenocarcinoma were absent in the setting of a healed mucosa at initial endoscopy,
the risk for development of adenocarcinoma was about 0.1% at 7 years' follow-up.[3]

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Gastro-oesophageal reflux disease Guidelines

Diagnostic guidelines

Europe

Practice guidelines on the use of esophageal manometry

Published by: Gruppo Italiano di Studio per la Motilita dell'Apparato Last published: 2016
Digerente; Societa Italiana di Gastroenterologia ed Endoscopia Digestiva;
Associazione Italiana Gastroenterologi ed Endoscopisti Digestivi
Ospedalieri

Recommendations for the management of gastroesophageal reflux disease

Published by: European Association of Endoscopic Surgery Last published: 2014

Catheterless oesophageal pH monitoring

Published by: National Institute for Health and Care Excellence Last published: 2006

GUIDELINES
North America

Chronic cough due to gastroesophageal reflux in adults: CHEST guideline

and expert panel report
Published by: American College of Chest Physicians Last published: 2016

Consensus statement of Society of Abdominal Radiology disease-focused

panel on barium esophagography in gastroesophageal reflux disease
Published by: Society of Abdominal Radiology Last published: 2016

The role of endoscopy in the management of GERD

Published by: American Society for Gastrointestinal Endoscopy Last published: 2015

Diagnosis and management of Barret t’s esophagus

Published by: American College of Gastroenterology Last published: 2015

ACR practice parameter for the performance of esophagrams and upper

gastrointestinal examinations in adults
Published by: American College of Radiology Last published: 2014

Diagnosis and management of gastroesophageal reflux disease

Published by: American College of Gastroenterology Last published: 2013

Medical position statement on the management of gastroesophageal reflux

disease
Published by: American Gastroenterological Association Last published: 2008

ACG practice guidelines: esophageal reflux testing

Published by: American College of Gastroenterology Last published: 2007

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 Gastro-oesophageal reflux disease Guidelines

North America

Canadian consensus conference on the management of gastroesophageal

reflux disease in adults - update 2004
Published by: Canadian Association of Gastroenterology Last published: 2005

Latin America

Gastroesophageal reflux disease: diagnosis

Published by: Federação Brasileira de Gastroenterologia; Sociedade Last published: 2011
Brasileira de Endoscopia Digestiva; Colégio Brasileiro de Cirurgia
Digestiva; Sociedade Brasileira de Pneumologia e Tisiologia

Asia
GUIDELINES

Asia-Pacific consensus on the management of gastro-oesophageal reflux

disease: an update focusing on refractory reflux disease and Barret t's
oesophagus
Published by: Asian Pacific Association of Gastroenterology Last published: 2016

Evidence-based clinical practice guidelines for gastroesophageal reflux

disease 2015
Published by: Japanese Society of Gastroenterology Last published: 2016

Treatment guidelines

Europe

Recommendations for the management of gastroesophageal reflux disease

Published by: European Association of Endoscopic Surgery Last published: 2014

Endoluminal gastroplication for gastro-oesophageal reflux disease

Published by: National Institute for Health and Care Excellence Last published: 2011

Endoscopic augmentation of the lower oesophageal sphincter using hydrogel

implants for the treatment of gastro-oesophageal reflux disease
Published by: National Institute for Health and Care Excellence Last published: 2007

North America

The risks and benefits of long-term use of proton pump inhibitors: expert
review and best practice advice
Published by: American Gastroenterological Association Last published: 2017

28 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: May 29, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
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Gastro-oesophageal reflux disease Guidelines

North America

Chronic cough due to gastroesophageal reflux in adults: CHEST guideline

and expert panel report
Published by: American College of Chest Physicians Last published: 2016

Treatment of gastroesophageal reflux disease (GERD) in adults

Published by: Alberta Clinical Practice Guidelines Last published: 2016

The role of endoscopy in the management of GERD

Published by: American Society for Gastrointestinal Endoscopy Last published: 2015

Diagnosis and management of Barret t’s esophagus

Published by: American College of Gastroenterology Last published: 2015

Diagnosis and management of gastroesophageal reflux disease

GUIDELINES
Published by: American College of Gastroenterology Last published: 2013

Surgical treatment of gastroesophageal reflux disease

Published by: Society of American Gastrointestinal and Endoscopic Last published: 2010
Surgeons

Medical position statement on the management of gastroesophageal reflux

disease
Published by: American Gastroenterological Association Last published: 2008

Canadian consensus conference on the management of gastroesophageal

reflux disease in adults - update 2004
Published by: Canadian Association of Gastroenterology Last published: 2005

Latin America

Gastroesophageal reflux disease: non-pharmacological treatment

Published by: Federação Brasileira de Gastroenterologia; Sociedade Last published: 2012
Brasileira de Endoscopia Digestiva; Colégio Brasileiro de Cirurgia
Digestiva; Sociedade Brasileira de Pneumologia; Associação Brasileira
de Otorrinolaringologia; Cirurgia Cérvico-Facial

Gastroesophageal reflux disease: drug therapy

Published by: Brazilian Federation of Gastroenterology; Brazilian Last published: 2011
Society of Digestive Endoscopy; Brazilian College of Digestive Surgery;
Brazilian Society of Pneumology and Phthisiology

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 Gastro-oesophageal reflux disease Guidelines

Asia

Asia-Pacific consensus on the management of gastro-oesophageal reflux

disease: an update focusing on refractory reflux disease and Barret t's
oesophagus
Published by: Asian Pacific Association of Gastroenterology Last published: 2016

Evidence-based clinical practice guidelines for gastroesophageal reflux

disease 2015
Published by: Japanese Society of Gastroenterology Last published: 2016

Oceania

Gastro-oesophageal reflux disease in adults

Published by: Gastroenterological Society of Australia Last published: 2011
GUIDELINES

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Gastro-oesophageal reflux disease Evidence scores

Evidence scores
1. Symptoms and healing in people with GORD and oesophagitis: there is poor-quality evidence that
antacids may reduce symptoms at 8 weeks, but not endoscopic healing at 4 to 8 weeks.
Evidence level C: Poor quality observational (cohort) studies or methodologically flawed randomized
controlled trials (RCTs) of <200 participants.

2. Prevention of persistent oesophagitis: there is medium-quality evidence that initial treatment with H2
antagonists reduces the risk of persistent oesophagitis compared with placebo in people with GORD.
However, there is good-quality evidence that H2 antagonists are less effective in this regard than
proton-pump inhibitors (PPIs).
Evidence level B: Randomized controlled trials (RCTs) of <200 participants, methodologically
flawed RCTs of >200 participants, methodologically flawed systematic reviews (SRs) or good quality
observational (cohort) studies.

3. Symptom reduction: there is poor-quality evidence regarding how initial treatment with lifestyle
changes (such as raising the head of the bed, or weight loss) affects symptoms of reflux.
Evidence level C: Poor quality observational (cohort) studies or methodologically flawed randomized
controlled trials (RCTs) of <200 participants.

4. Prevention of persistent oesophagitis: there is good-quality evidence that proton-pump inhibitors (PPIs)
are more effective at preventing persistent oesophagitis than placebo in people with GORD, and are
more effective than H2 antagonists.
Evidence level A: Systematic reviews (SRs) or randomized controlled trials (RCTs) of >200
participants.

5. Relapse rates: there is good-quality evidence that proton-pump inhibitors (PPIs) reduce relapse of
oesophagitis or reflux symptoms at 6 to 12 months in people with healed oesophagitis, and more
effectively than H2 antagonists.
Evidence level A: Systematic reviews (SRs) or randomized controlled trials (RCTs) of >200
participants.

6. Improvement of reflux symptoms and oesophagitis in chronic GORD: there is poor-quality evidence
that open fundoplication may be more effective than antacids or H2 antagonists at reducing reflux and
at improving the endoscopic grade of oesophagitis (timescale not specified) in people with chronic
GORD and oesophagitis, but not at improving endoscopic appearance after 10 years.
Evidence level C: Poor quality observational (cohort) studies or methodologically flawed randomized
EVIDENCE SCORES

controlled trials (RCTs) of <200 participants.

7. Symptom severity: there is poor-quality evidence comparing laparoscopic fundoplication with proton
pump inhibition or with open surgery.

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31
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 Gastro-oesophageal reflux disease Evidence scores
Evidence level C: Poor quality observational (cohort) studies or methodologically flawed randomized
controlled trials (RCTs) of <200 participants.

8. Symptom management: we found no randomised controlled trials on the effects of lifestyle measures
on the long-term management of reflux oesophagitis.
Evidence level C: Poor quality observational (cohort) studies or methodologically flawed randomized
controlled trials (RCTs) of <200 participants.
EVIDENCE SCORES

32 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: May 29, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
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Gastro-oesophageal reflux disease References

Key articles
• Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal

REFERENCES
reflux disease. Am J Gastroenterol. 2013 Mar;108(3):308-28. Full text Abstract

• Vakil N, van Zanten SV, Kahrilas P, et al. The Montreal definition and classification of
gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006
Aug;101(8):1900-20. Abstract

• World Gastroenterology Organisation. Global perspective on gastroesophageal reflux disease.

October 2015 [internet publication]. Full text

• Muthusamy VR, Lightdale JR, Acosta RD, et al; ASGE Standards of Practice Committee. The role
of endoscopy in the management of GERD. Gastrointest Endosc. 2015;81(6):1305-10. Full text
Abstract

• Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors:
expert review and best practice advice from the American Gastroenterological Association.
Gastroenterology. 2017 Mar;152(4):706-15. Abstract

• Ness-Jensen E, Hveem K, El-Serag H, et al. Lifestyle intervention in gastroesophageal reflux disease.

Clin Gastroenterol Hepatol. 2016 Feb;14(2):175-82. Full text Abstract

• Zhang H, Dong D, Liu Z, et al. Revaluation of the efficacy of magnetic sphincter augmentation for
treating gastroesophageal reflux disease. Surg Endosc. 2016 Sep;30(9):3684-90. Abstract

References
1. Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal
reflux disease. Am J Gastroenterol. 2013 Mar;108(3):308-28. Full text Abstract

2. Vakil N, van Zanten SV, Kahrilas P, et al. The Montreal definition and classification of
gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006
Aug;101(8):1900-20. Abstract

3. Kahrilas PJ, Shaheen NJ, Vaezi MF, et al. American Gastroenterological Association medical
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4. Armstrong D, Marshall JK, Chiba N, et al; Canadian Association of Gastroenterology GERD

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5. Leason SR, Barham HP, Oakley G, et al. Association of gastro-oesophageal reflux and chronic
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BMJ Best Practice topics are regularly updated and the most recent version
33
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
 Gastro-oesophageal reflux disease References
6. Sidhwa F, Moore A, Alligood E, et al. Diagnosis and treatment of the extraesophageal manifestations
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subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
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24. Muthusamy VR, Lightdale JR, Acosta RD, et al; ASGE Standards of Practice Committee. The role
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30. Eliakim R, Sharma VK, Yassin K, et al. A prospective study of the diagnostic accuracy of PillCam
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33. Kahrilas PJ. Clinical practice. Gastroesophageal reflux disease. N Engl J Med. 2008 Oct
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34. Hirano I, Richter JE; Practice Parameters Committee of the American College of Gastroenterology.
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Full text Abstract

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BMJ Best Practice topics are regularly updated and the most recent version
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of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
 Gastro-oesophageal reflux disease References
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40. Guo H, Ma H, Wang J. Proton pump inhibitor therapy for the treatment oflaryngopharyngeal reflux: a
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41. Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional
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42. Armstrong D, Bennett JR, Blum AL, et al. The endoscopic assessment of esophagitis: a progress
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43. Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors:
expert review and best practice advice from the American Gastroenterological Association.
Gastroenterology. 2017 Mar;152(4):706-15. Abstract

44. Ness-Jensen E, Hveem K, El-Serag H, et al. Lifestyle intervention in gastroesophageal reflux disease.
Clin Gastroenterol Hepatol. 2016 Feb;14(2):175-82. Full text Abstract

45. Ichikawa H, Sugimoto M, Sugimoto K, et al. Rapid metabolizer genotype of CYP2C19 is a risk factor of
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46. Haastrup P, Paulsen MS, Begtrup LM, et al. Strategies for discontinuation of proton pump inhibitors: a
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47. Boghossian TA, Rashid FJ, Thompson W, et al. Deprescribing versus continuation of chronic proton
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48. Du X, Hu Z, Yan C, et al. A meta-analysis of long follow-up outcomes of laparoscopic Nissen (total)
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36 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: May 29, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
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51. Maret-Ouda J, Wahlin K, El-Serag HB, et al. Association between laparoscopic antireflux surgery and
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52. Garg SK, Gurusamy KS. Laparoscopic fundoplication surgery versus medical management for
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53. Ganz RA, Peters JH, Horgan S, et al. Esophageal sphincter device for gastroesophageal reflux
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54. Saino G, Bonavina L, Lipham JC, et al. Magnetic sphincter augmentation for gastroesophageal reflux
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55. Zhang H, Dong D, Liu Z, et al. Revaluation of the efficacy of magnetic sphincter augmentation for
treating gastroesophageal reflux disease. Surg Endosc. 2016 Sep;30(9):3684-90. Abstract

56. Sheu EG, Nau P, Nath B, et al. A comparative trial of laparoscopic magnetic sphincter augmentation
and Nissen fundoplication. Surg Endosc. 2015 Mar;29(3):505-9. Abstract

57. Yang YX, Lewis JD, Epstein S, et al. Long-term proton-pump inhibitor therapy and risk of hip fracture.
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58. Laheij RJ, Sturkenboom MC, Hassing RJ, et al. Risk of community-acquired pneumonia and use of
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59. Herzig SJ, Howell MD, Ngo LH, et al. Acid-suppressive medication use and the risk for hospital-
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60. Chen J, Yuan YC, Leontiadis GI, et al. Recent safety concerns with proton pump inhibitors. J Clin
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61. Juurlink DN, Gomes T, Ko DT, et al. A population-based study of the drug interaction between proton
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subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
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38 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: May 29, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
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82. Sharma P. Clinical practice. Barrett's esophagus. N Engl J Med. 2009 Dec 24;361(26):2548-56.
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83. Hirota WK, Zuckerman MJ, Adler DG, et al. ASGE guideline: the role of endoscopy in the surveillance
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This PDF of the BMJ Best Practice topic is based on the web version that was last updated: May 29, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
39
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2018. All rights reserved.
 Gastro-oesophageal reflux disease Images

Images
IMAGES

Figure 1: Moderate to severe oesophagitis with multiple linear, clean-based oesophageal ulcers
From the collection of Dr Douglas G. Adler; used with permission

40 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: May 29, 2018.
BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
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Gastro-oesophageal reflux disease Images
Figure 2: Barrett's segment lined by gastric-type epithelium without intestinal metaplasia in the form of goblet
cells (magnification ×100). (A) Mucin staining using Alcian Blue-Periodic Acid Schiff showing neutral magenta
colour (mucin of gastric epithelial type); (B) H&E staining reveals a Barrett’s oesophagus segment lined by
gastric-type epithelium without intestinal metaplasia but with features of high-grade dysplasia
Lieberman ELB, Lao-Sirieix P, Saeed I, et al. The definition and management of Barrett’s oesophagus: a
case report, review of the literature and a suggestion for the future. BMJ Case Reports. 2009; doi:10.1136/
bcr.07.2008.0450

IMAGES
Figure 3: Upper gastrointestinal endoscopy revealing a fistula related to oesophageal carcinoma (arrow)
Wang S-C, Tseng J-C, Lee R-M, et al. Tracheo-oesophageal fistula in a patient with oesophageal squamous
cell carcinoma. BMJ Case Reports. 2009; doi:10.1136/bcr.09.2008.0865

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 Gastro-oesophageal reflux disease Disclaimer

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Contributors:

// Authors:

Marc J. Zuckerman, MD
Professor of Medicine
Chief of Division of Gastroenterology, Texas Tech University Health Sciences Center, El Paso, TX
DISCLOSURES: MJZ has been a speaker for Synergy Pharmaceuticals and for Allergan Pharmaceuticals.
He is an author of a reference cited in this monograph.

Andres F. Carrion, MD
Medical Director of Gastrointestinal Endoscopy
Assistant Professor of Medicine, Division of Gastroenterology, Texas Tech University Health Sciences
Center, El Paso, TX
DISCLOSURES: AFC declares that he has no competing interests.

// Acknowledgements:
Dr Marc J. Zuckerman and Dr Andres F. Carrion would like to gratefully acknowledge Dr. Sheila Feit and Dr.
Mohamed Othman, previous contributors to this topic. SF declares that she has no competing interests. MO
has acted as a consultant for Olympus.

// Peer Reviewers:

Lars Aabakken, MD
Professor of Medicine
Chief of GI Endoscopy, Rikshospitalet University Hospital, Oslo, Norway
DISCLOSURES: LA declares that he has no competing interests.

Lise Lot te Gluud, MD, DMSc

Consultant
Department of Internal Medicine, Copenhagen University Hospital, Hellerup, Denmark
DISCLOSURES: LLG declares that she has no competing interests.

Gary W. Falk, MD, MS

Professor of Medicine
Department of Gastroenterology & Hepatology, Center for Swallowing & Esophageal Disorders, Cleveland
Clinic, Cleveland, OH
DISCLOSURES: GWF has received fees from: Astra Zeneca (consultant, speakers bureau, grant support);
Takeda (grant support); Pentax (speaker, travel); Wyeth (consultant); and C2 Therapeutics (consultant).