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these conclusions was weighed using US Preventive Services
Task Force (USPSTF) grades. Of note, none of the formulated
practice recommendations were judged to be sufficiently un-
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burn symptoms of insufficient frequency or severity to be
perceived as troublesome by the patient (after assurance of
their benign nature) do not meet the Montreal definition of
A
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GASTROENTEROLOGY 2008;135:1383–1391
ivocal to be proposed as performancemeasures for gauging
ality of care.
Diagnosis and Initial Therapy
1. What Is an Operational Definition of
GERD? What Is the Distinction Between
GERD and Episodic Heartburn?
There can be no criterion standard definition of
RD because the threshold distinction between physio-
ic reflux and reflux disease is ultimately arbitrary. Hence,
se questions can only be answered by opinion (USPSTF
de not applicable). Fortuitously, a recent consensus in
fining GERD (the Montreal consensus) emanated from a
nel of world experts. The Montreal definition was
a symptomatic esophageal GERD syndrome.
2. What Is the Efficacy of Lifestyle
Modifications for GERD? Which Elements
Should Be Recommended and in Which
Circumstances?
Grade B: recommended with fair evidence that it
improves important outcomes
I. Weight loss should be advised for overweight or obese
patients with esophageal GERD syndromes.
GA INSTITUTE
merican Gastroenterological Associ
e Management of Gastroesophagea
e American Gastroenterological Association (AGA) Institute
iew, a community-based gastroenterologist (Stephen W. Hiltz, M
ack, MD, Medical Director, Policy Resources Technology Ev
geon (Irvin M. Modlin, MD), a patient advocate (Gregory
troenterologist with expertise in health services research (Philip
actice and Quality Management Committee (John Allen, MD,
nagement and Economics Committee and the AGA Institute C
n the development of this medical position statement, 12
broad questions pertinent to diagnostic and management
ategies for patients with gastroesophageal reflux disease
ERD) were developed by interaction among the authors of
technical review,1 representatives from the American Gas-
enterological Association (AGA) Institute Council, and the
A Institute Clinical Practice and Quality Management
mmittee. The questions were designed to encapsulate the
jormanagement issues encountered in patientswithGERD
current clinical practice. The issue of management of Bar-
t’s esophagus was intentionally excluded, because this will
the focus of a subsequent medical position statement. For
h question, a comprehensive literature search was con-
cted, pertinent evidence reviewed, and the quality of relevant
ta evaluated. The details of development methodology, lit-
ture search methodology, and literature search yield associ-
d with each of the questions are available on the AGA
titute Web site as a separate document.2 The resultant
clusions were based on the best available evidence or, in the
ence of quality evidence, expert opinion. The strength of
opted in the technical review as a suitable framework
on which to build management recommendations. The
n Medical Position Statement on
eflux Disease
ical Position Panel consisted of the authors of the technical
MBA, AGAF), an insurance provider representative (Edgar
tion Center, BlueCross BlueShield Association), a general
e), a primary care physician (Steve P. Johnson, MD), a
Schoenfeld, MD), the Chair of the AGA Institute Clinical
A, AGAF), and the Chair of the AGA Institute Practice
Advisor (Joel V. Brill, MD, AGAF).
ntreal consensus defined GERD as “a condition which
velops when the reflux of stomach contents causes trou-
some symptoms and/or complications.” Symptoms are
oublesome” if they adversely affect an individual’s well-
ng. Esophageal GERD syndromes are categorized as
se that are symptom based and those that are defined by
sue injury, while the extraesophageal syndromes are clas-
ed as of established or proposed association with GERD,
nowledging that while the evidence on hand is sufficient
link these syndromes to reflux, it is insufficient to estab-
causation.
A distinguishing feature of the Montreal definition is
t it does not use the term “nonerosive reflux disease” but
her subdivides esophageal syndromes into symptomatic
dromes and syndromes with esophageal injury. Hence,
ctional heartburn does not fit theMontreal definition of
RD, whereas it is included under the umbrella of non-
sive reflux disease. The distinction between GERD and
isodic heartburn in theMontreal definition is in the word
oublesome.” In the absence of esophageal injury, heart-
© 2008 by the AGA Institute
0016-5085/08/$34.00
doi:10.1053/j.gastro.2008.08.045
II
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A
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1384 AMERICAN GASTROENTEROLOGICAL ASSOCIATION INSTITUTE GASTROENTEROLOGY Vol. 135, No. 4
. Elevation of the head of the bed for selected patients
who are troubled with heartburn or regurgitation when
recumbent. Other lifestyle modifications including, but
not limited to, avoiding late meals, avoiding specific
foods, or avoiding specific activities should be tailored
to the circumstances of the individual patient.
rade Insuff: no recommendation, insufficient ev-
ence to recommend for or against
Broadly advocating lifestyle changes for all (as opposed
to selected) patients with GERD.
Broadly speaking, lifestyle modifications recom-
nded for GERD fall into 3 categories: (1) avoidance of
ds that may precipitate reflux (eg, coffee, alcohol,
ocolate, fatty foods), (2) avoidance of acidic foods that
y precipitate heartburn (eg, citrus, carbonated drinks,
icy foods), and (3) adoption of behaviors that may
uce esophageal acid exposure (weight loss, smoking
sation, raising the head of the bed, and avoiding re-
mbency for 2–3 hours after meals). The problem with
se is that there are simply too many recommendations
d each is too narrowly applicable to enforce the whole
on every patient. However, it is also clear that there are
bsets of patients who may benefit from specific lifestyle
difications, and it is good practice to make those
ommendations to those patients based on their spe-
c history. A patient with symptoms of nighttime
artburn or regurgitation of sufficient severity to dis-
b his or her sleep despite acid suppressive therapy may
nefit from elevation of the head of the bed. Similarly, a
tient who consistently experiences troublesome heart-
rn after ingestion of alcohol, coffee, or spicy foods will
nefit from avoidance of these. Finally, if a patient is
erweight or obese, it is reasonable to suggest weight
s as an intervention that may prevent, or at least
stpone, the need for acid suppression.
3. How Do Antisecretory Therapies Compare
in Efficacy and Under What Circumstances
Might One Be Preferable to Another? What Is
an Acceptable Upper Limit of Empirical
Therapy in Patients With Suspected Typical
Esophageal GERD Syndromes Before
Performing Esophagogastroduodenoscopy?
rade A: strongly recommended based on good evi-
ence that it improves important health outcomes
Antisecretory drugs for the treatment of patients with
esophageal GERD syndromes (healing esophagitis and
symptomatic relief). In these uses, proton pump inhibi-
tors (PPIs) are more effective than histamine2 receptor
antagonists (H2RAs), which are more effective than
placebo.
rap
an
ing
rade B: recommended with fair evidence that it
proves important outcomes
. Twice-daily PPI therapy for patients with an esophageal
syndrome with an inadequate symptom response to
once-daily PPI therapy.
. A short course or as-needed use of antisecretory drugs in
patients with a symptomatic esophageal syndrome
without esophagitis when symptom control is the pri-
mary objective. For a short course of therapy, PPIs are
more effective than H2RAs, which are more effective
than placebo.
rade D: recommend against, fair evidence that it
ineffective or harms outweigh benefits
Metoclopramide as monotherapy or adjunctive therapy
in patients with esophageal or suspected extraesophageal
GERD syndromes.
The current consensus is that empirical therapy is
propriate initial management for patients with uncom-
cated heartburn. Abundant data support treating pa-
nts with esophageal GERD syndromes with antisecretory
gs, and there is ample evidence that, as a drug class, PPIs
more effective in these patients than are H2RAs, which
in turn more effective than placebo. However, the data
porting the use of PPIs (or H2RAs) in doses higher than
standard are weak. Similarly, there is no evidence of
proved efficacy by adding a nocturnal dose of an H2RA to
ice-daily PPI therapy. A notable disconnect between clin-
l trial data and clinical practice is in the use of PPIs twice
ily. Almost all efficacy data on these medications are from
ce-daily dosing studies, even though the pharmacody-
mics of the drugs logically supports twice-daily dosing.
nce, guidance on this issue comes primarily from expert
inion, which is essentially unanimous in recommending
ice-daily dosing of PPIs to improve symptom relief in
tients with an esophageal GERD syndrome with an un-
isfactory response to once-daily dosing. Patients whose
artburn has not adequately responded to twice-daily PPI
rapy should be considered treatment failures, making
t a reasonable upper limit for empirical therapy.
Circumstances in which one antisecretory drug might be
ferable to another primarily relate to side effects or when
onset of effect is a prime consideration. The most
mon side effects of PPIs are headache, diarrhea, consti-
tion, and abdominal pain. Switching among alternative
I drugs or to a lower dose can usually circumvent these
e effects. As for the issue of onset of action, this primarily
rtains to on-demand therapy. If a patient intends to take
rug only in response to symptoms, then it should be a
idly acting drug. The most rapidly acting agents are
tacids, the efficacy of which can be sustained by combin-
them with an H2RA or a PPI.
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October 2008 AMERICAN GASTROENTEROLOGICAL ASSOCIATION INSTITUTE 1385
4. What Is the Role and Priority of Diagnostic
Tests (Endoscopy With or Without Biopsy,
Esophageal Manometry, Ambulatory pH
Monitoring, Impedance-pH Monitoring) in the
Evaluation of Patients With Suspected
Esophageal GERD Syndromes?
rade B: recommended with fair evidence that it
proves important outcomes
I. Endoscopy with biopsy for patients with an esophageal
GERD syndrome with troublesome dysphagia. Biopsies
should target any areas of suspected metaplasia, dysplasia,
or in the absence of visual abnormalities, normal mucosa
(at least 5 samples to evaluate for eosinophilic esophagitis).
I. Endoscopy to evaluate patients with a suspected esophageal
GERD syndrome who have not responded to an empirical
trial of twice-daily PPI therapy. Biopsies should target any
area of suspected metaplasia, dysplasia, or malignancy.
I. Manometry to evaluate patients with a suspected esophageal
GERD syndrome who have not responded to an empirical
trial of twice-daily PPI therapy and have normal findings on
endoscopy.Manometry will serve to localize the lower esoph-
ageal sphincter for potential subsequent pH monitoring, to
evaluate peristaltic function preoperatively, and to diagnose
subtle presentations of the major motor disorders. Evolving
information suggests that high-resolution manometry has
superior sensitivity to conventional manometry in recogniz-
ing atypical cases of achalasia and distal esophageal spasm.
. Ambulatory impedance-pH, catheter pH, or wireless pH
monitoring (PPI therapy withheld for 7 days) to evaluate
patients with a suspected esophageal GERD syndrome
who have not responded to an empirical trial of PPI
therapy, have normal findings on endoscopy, and have no
major abnormality on manometry. Wireless pH monitor-
ing has superior sensitivity to catheter studies for detect-
ing pathological esophageal acid exposure because of the
extended period of recording (48 hours) and has also
shown superior recording accuracy compared with some
catheter designs.
rade Insuff: no recommendation, insufficient ev-
ence to recommend for or against
I. Using alarm symptoms (other than troublesome dys-
phagia) as a screening tool to identify patients with
GERD at risk for esophageal adenocarcinoma.
I. Combined impedance-pH, catheter pH, or wireless pH
monitoring studies to distinguish hypersensitivity syn-
dromes from functional syndromes, the distinction being
that in hypersensitivity syndromes symptoms are attrib-
utable to reflux events, whereas in functional syndromes
they are not.
I. Combined impedance-pH, catheter pH, or wireless pH
esophageal monitoring studies performed while taking
PPIs.
pe
mu
gea
Diagnostic testing for esophageal GERD syndromes
nvoked in 3 broad scenarios: (1) to avert misdiagnosis, (2)
identify complications of reflux disease, and (3) in the
luation of empirical treatment failures. The discussion of
sdiagnosis and identifying complications of reflux dis-
e usually revolves around the concept of “alarm features”
t are suggestive of an alternative diagnosis. Important
ernative diagnoses include coronary artery disease, gall-
dder disease, gastric or esophageal malignancy, peptic
er disease, and eosinophilic, infectious, or caustic esoph-
tis. High-quality evidence supporting the broad utility of
rm features as a diagnostic tool is quite limited. However,
ividual alarm features with the best performance for
ntifying esophageal or gastric malignancies are weight
s, dysphagia, and epigastric mass on examination, mak-
it appropriate to evaluate these with endoscopy. A ca-
t in the endoscopic evaluation of dysphagia is that the
doscopist should have a low threshold for obtaining
ltiple (preferably at least 5) esophageal mucosal biopsy
cimens to evaluate for eosinophilic esophagitis.
The other broad scenario under which diagnostic testing
erformed is in the evaluation of troublesome symptoms
t have not adequately responded to empirical twice-daily
I therapy. Did therapy fail because of troublesome symp-
s attributable to reflux that did not resolve with PPI
rapy or because the symptoms under consideration are
t attributable to reflux? Endoscopy is again the first
gnostic test to consider because it may demonstrate
rrett’s metaplasia, stricture, or an alternative upper gas-
intestinal diagnosis. After a normal endoscopy, priority
uld be given to identifying conditions for which an
ective alternative therapy exists. In the case of GERD, the
ly alternative, potentially more effective, therapy is anti-
ux surgery. High-quality evidence on the efficacy of an-
eflux surgery exists only for esophagitis and/or excessive
tal esophageal acid exposure when PPI therapy is with-
ld. Another requirement for antireflux surgery is that
e peristaltic function be preserved. Finally, it is impor-
t to identify alternative diagnoses that may masquerade
GERD: functional heartburn, atypical cases of achalasia,
distal esophageal spasm. Given these priorities, the sec-
d diagnostic evaluation should be esophageal manome-
and the third should then be to ascertain whether or not
re is excessive esophageal acid exposure when PPI ther-
y is withheld. Whether this examination should be per-
med with the patient on acid suppressive therapy is
bated. The unclear relevance of “normative” data for im-
dance-pH studies performed on PPI therapy makes it
ficult to interpret such studies. If normal values are not
justed, then such an on-PPI study could show an un-
ivocal PPI nonresponse. That, however, rarely occurs. At
s point in the diagnostic algorithm, troublesome symp-
s of heartburn, chest pain, regurgitation, or dysphagia
rsist despite normal findings on endoscopy (including
cosal biopsy in the case of dysphagia), normal esopha-
l acid exposure, and a manometry study that ruled out a
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1386 AMERICAN GASTROENTEROLOGICAL ASSOCIATION INSTITUTE GASTROENTEROLOGY Vol. 135, No. 4
jor motor disorder. Current thinking is that the major
aining possibilities are a hypersensitivity syndrome or a
ctional syndrome, the distinction being that in the case
a hypersensitivity syndrome symptoms are attributable to
ux events, whereas in the case of a functional syndrome
y are not. This is a subtle distinction and a domain in
ich there is currently no high-quality evidence support-
one management approach or another.
5. What Are the Unique Management
Considerations in Patients With Suspected
Reflux Chest Pain Syndrome?
rade A: strongly recommended based on good ev-
ence that it improves important health outcomes
Twice-daily PPI therapy as an empirical trial for patients
with suspected reflux chest pain syndrome after a cardiac
etiology has been carefully considered.
Chest pain indistinguishable from ischemic car-
c pain can be caused by GERD. Because the morbidity
d mortality associated with ischemic heart disease is
bstantially greater than that of GERD and because of
impressive array of available therapeutic interven-
ns, this diagnosis must be thoroughly considered be-
e accepting a diagnosis of reflux chest pain syndrome.
ce ischemic heart disease has been adequately consid-
d, the relative rarity of esophageal motor disorders in
s group of patients, as well as results from empirical
atment trials of acid suppressive therapy, suggest that
RD may be the next most likely etiology. Meta-analy-
of placebo-controlled treatment trials in patients with
spected reflux chest pain suggest benefit from a 4-week
al with twice-daily PPI therapy. If a patient continues
have chest pain despite this course of therapy, diag-
stic testing with esophageal manometry and pH or
pedance-pH monitoring can exclude motility disorders
refractory reflux symptoms.
6. What Is the Best Initial Management for
Patients With Suspected Extraesophageal
Reflux Syndromes (Asthma, Laryngitis,
Cough)? What Are the Unique Management
Considerations With Each? What Is the
Appropriate Dose and Course of Antisecretory
Therapy in Each?
rade B: recommended with fair evidence that it
proves important outcomes
Acute or maintenance therapy with once- or twice-daily
PPIs (or H2RAs) for patients with a suspected extra-
esophageal GERD syndrome (laryngitis, asthma) with a
concomitant esophageal GERD syndrome.
do
tra
da
rade D: recommend against, fair evidence that it
ineffective or harms outweigh benefits
Once- or twice-daily PPIs (or H2RAs) for acute treat-
ment of patients with potential extraesophageal GERD
syndromes (laryngitis, asthma) in the absence of a con-
comitant esophageal GERD syndrome.
rade Insuff: no recommendation, insufficient ev-
ence to recommend for or against
Once- or twice-daily PPIs for patients with suspected
reflux cough syndrome.
Chronic cough, laryngitis, and asthma have an
ablished association with GERD on the basis of pop-
tion-based studies. However, cough, laryngitis, and
hma have a multitude of potential etiologies other
n GERD, making them nonspecific for GERD. Fur-
rmore, the causal relationship of GERD with these
nspecific syndromes in the absence of a con