American College of Gastroenterology
Update Guidelines for the Diagnosis and Treatment of Gastroesophageal Reflux Disease
Updated Guidelines for the Diagnosis and Treatment of Gastroesophageal
Kenneth R. DeVault, M.D., F.A.C.G., Donald O. Castell, M.D., F.A.C.G., and
The Practice Parameters Committee of the American College of
Guidelines for the diagnosis and treatment of gastroesophageal reflux
disease (GERD) were published by the American College of Gastroenterology
in 1995 (1). These and other guidelines undergo periodic review.
Significant advances have been made in the area of GERD over the past
several years, leading us to review and revise our previous guidelines
statements. These advances have included an increase in our comfort with
the chronic use of proton pump inhibitors and an increased acceptance of
laparoscopic antireflux surgery, among other factors. These and the
original guidelines are intended to apply to all physicians who address
GERD and are intended to indicate the preferable, but not only acceptable,
approach. Physicians must always choose the course best suited to the
individual patient and the variables that exist at the moment of the
decision. These guidelines are intended to apply to adult patients with
the symptoms, tissue damage, or both that result from the reflux of
gastric contents into the esophagus. For the purpose of these guidelines
GERD is defined as chronic symptoms or mucosal damage produced by the
abnormal reflux of gastric contents into the esophagus.
Both these and the original guidelines were developed under the auspices
of the American College of Gastroenterology and its Practice Parameters
Committee, and approved by the Board of Trustees. The world literature was
reviewed extensively for the original guidelines and was once again
reviewed using the National Library of Medicine database. All appropriate
studies were reviewed and any additional studies found in the reference
list of these papers were obtained and reviewed. Evidence was evaluated
along a hierarchy, with randomized controlled trials given the greatest
weight. Abstracts presented at national and international meetings were
only used when unique data from ongoing trials were presented. When
scientific data were lacking, recommendations were based on expert
consensus. During preparation, the guidelines were reviewed by the
American Gastroenterological Association and the American Society for
Gastrointestinal Endoscopy. Recommendations and comments obtained from
these reviews were incorporated into the final document whenever possible.
Empiric Therapy for GERD
If the patient's history is typical for uncomplicated GERD, an initial
trial of empirical therapy (including lifestyle modification) is
appropriate. Patients in whom empirical therapy is unsuccessful or who
have symptoms suggesting complicated disease should have further
If the patient's history is typical for uncomplicated GERD, an initial
trial of empirical therapy (including lifestyle modification) is
appropriate. Patients in whom empirical therapy is unsuccessful, or who
have symptoms suggesting complicated disease, should have further
diagnostic testing. Selected individuals who have longstanding symptoms or
who require continuous therapy may need endoscopic screening for Barrett's
Symptoms that are highly specific for GERD (when the predominant or only
symptoms) include heartburn (pyrosis), regurgitation, or both, which often
occur after meals (especially large or fatty meals) (2). These symptoms
are often aggravated by recumbency or bending and are relieved by
antacids. The combination of symptoms and endoscopic changes are highly
specific (97%) for GERD (confirmed with pH testing) (3). Expert opinion
holds that it is appropriate to offer empirical therapy for GERD to
patients with symptoms consistent with GERD. It is also reasonable to
assume a diagnosis of GERD in patients who respond to appropriate therapy.
Further diagnostic testing should be considered under four circumstances:
lack of response to therapy, warning symptoms (Table 1), chronic symptoms
in a patient at risk for Barrett's esophagus, or need for continuous
chronic therapy. Patients who do not respond to therapy often have another
cause for their symptoms, but this lack of response does not always
exclude reflux as a possibility. Even when the most effective therapy for
GERD is prescribed, some patients will continue to reflux acid (4). The
purpose of evaluating patients who have warning symptoms is to exclude
complications of GERD (esophageal strictures, carcinomas, etc). Other
guidelines have been published that examine Barrett's esophagus in detail
(5). In brief, certain patients with long-term symptoms (either with or
without therapy) are at an increased risk for the development of Barrett's
esophagus. Because we cannot be assured that partial (or even complete)
control of acid changes this progression, the number of years of
antireflux therapy may need to be considered in the calculation of when to
search for Barrett's esophagus. The concept of symptoms predicting the
presence of Barrett's esophagus has been challenged by reports suggesting
that both the frequency and severity of reflux symptoms are poorly
predictive of the presence of Barrett's esophagus (6).
Warning Symptoms Suggesting Complicated GERD
Choking (acid causing coughing, shortness of breath , or
Endoscopy in GERD
Endoscopy with biopsy is the primary technique for evaluating mucosal
integrity. If unavailable, double-contrast radiography may be used.
Endoscopy is the technique of choice for evaluating the mucosa for
esophagitis. The diagnosis of Barrett's esophagus requires biopsy to
search for intestinal metaplasia.
Endoscopy allows direct visualization of the esophageal mucosa. This is
the only reliable method for the diagnosis of Barrett's esophagus. A
reticular pattern on barium esophagram is neither sensitive (26%) nor
specific (50%) when compared with endoscopy with biopsy (7). Barium
radiography is reasonably accurate in cases of severe (98.7%) or moderate
(81.6%) esophagitis, but is much less accurate with mild esophagitis
(24.6%) (8, 9, 10, 11). Finally, reflux of barium during radiographic
evaluation is only positive in 25-75% of symptomatic patients and is
falsely positive in as many as 20% of normal controls (12, 13). Patients
with hiatal hernias or who reflux barium at fluoroscopy have more acid
exposure by ambulatory pH testing, but these findings have poor
specificity and sensitivity and should not be used as a screening test for
GERD (14). These factors limit the usefulness of barium radiography in the
routine diagnosis of GERD.
Endoscopic biopsy is needed to determine the presence of Barrett's
epithelium. The issues surrounding both routine and short-segment
Barrett's are covered in another guidelines statement (5). Patients with
both typical and atypical manifestations of GERD will often have
normal-appearing esophageal mucosa. These cases must be confirmed with
other methods (pH testing or therapeutic trial). There is little value for
histological examination of normal-appearing squamous mucosa to either
confirm or exclude pathological acid reflux (15, 16).
pH and Provocative Testing
Ambulatory pH testing helps to confirm gastroesophageal reflux in patients
with persistent symptoms without evidence of mucosal damage and with
noncardiac chest pain or reflux-associated pulmonary and upper respiratory
symptoms, and to monitor the esophageal acid exposure of a patient with
refractory symptoms. Provocative tests have a limited usefulness in the
routine diagnosis and therapy of GERD.
Although endoscopy allows for the evaluation of esophageal mucosa, the
presence or absence of mucosal injury does not provide proof that the
patient's symptoms are or are not related to GERD. Many patients with
typical GERD symptoms and increased esophageal acid exposure do not have
esophagitis (17). Patients with symptomatic, but not excessive,
gastroesophageal reflux have persistence of symptoms and requirements for
therapy similar to patients with excessive reflux, but are less likely to
have endoscopic findings (18, 19). This endoscopic-negative form of GERD
produces symptoms and illness behavior identical to that of GERD with
endoscopic findings (20). Ambulatory pH testing allows the identification
of patients with excess esophageal acid exposure and those with symptoms
that correlate with esophageal acid (with either normal or abnormal total
acid exposure). Good reproducibility (84-93%) and sensitivity and
specificity (96%) have been reported (21, 22). Some additional papers have
provided cause for concern. Normal acid exposure was reported in as many
as 29% of patients with documented esophagitis and differences were found
in the simultaneous acid exposure recorded by two attached probes (23,
24). Despite these limitations, ambulatory pH testing remains the best
method to study the actual amount of reflux occurring in a given patient.
Patients with typical reflux symptoms and a normal endoscopy, but who
respond to antireflux therapy, will not benefit greatly from a pH study.
Ambulatory pH testing while taking reflux therapy may also be of benefit
in the patient with refractory symptoms (25).
The most commonly used provocative test of the esophagus is the Bernstein
test of mucosal sensitivity to acid. If the subject's symptoms are
provoked by acid and not by a normal saline control, the test is highly
specific for GERD, but unfortunately much less sensitive (26). The
Bernstein test may therefore establish that a patient's symptoms are
related to GERD, but cannot exclude reflux and also cannot differentiate
between degrees of reflux or esophagitis.
An empirical trial of therapy with full- or double-dose proton pump
inhibitor (PPI) has been suggested as a "test" for GERD. Relief of
symptoms with 1 wk of omeprazole 20 mg twice daily had a sensitivity of
75% and a specificity of 55% when compared with endoscopy and ambulatory
pH testing (27). In another study, using pH as the gold-standard, an
omeprazole trial had a positive and negative predictive value of 68% and
63%, respectively, and when the omeprazole trial was considered the
standard, the pH test had identical positive and negative predictive
values (28). Neither a PPI trial nor ambulatory pH testing should be
considered to provide absolute proof or disproof of GERD and in difficult
cases both may be needed for the highest diagnostic certainty. An
empirical trial of PPI has also been advocated as a diagnostic test in
patients with atypical symptoms or signs such as chronic laryngitis (29)
or unexplained chest pain (30).
Esophageal manometry is indicated and in certain complicated cases may be
helpful before an antireflux procedure is performed.
Esophageal manometry should be used to facilitate placement of ambulatory
pH probes and to guide antireflux surgery.
The accurate placement of esophageal pH probes requires knowledge of the
location of the lower esophageal sphincter (LES) (31, 32). This usually
requires intubation with a manometry catheter and provides an opportunity
for full manometry. There now have been several reports that show adequate
placement of pH tubes using a combined pH/pressure measurement system,
which negates the need for full manometry (33, 34). Esophageal manometry
to document the presence of effective esophageal peristalsis is useful in
patients in whom antireflux surgery is being considered (35). Patients who
have ineffective peristalsis may need to either avoid surgery or undergo
an alternative (i.e., less tight) procedure (36). In a series of 107
patients, manometry changed the therapy offered in 10% of patients
referred for antireflux surgery (37). Surgeons will often elect to perform
a partial fundoplication in patients who have peristaltic dysfunction of
the esophagus by manometry (38). These reports suggest, but do not prove,
that better reflux control is achieved with a complete (Nissen)
fundoplication than with a partial (Toupet) and that in a patient with
less effective esophageal peristalsis, the risk of dysphagia is higher
with the complete fundoplication. If these assumptions are true, manometry
should be mandatory before fundoplication to choose the best surgery for
the individual patient. Absolute LES pressure has been suggested to
inversely correlate with esophageal acid exposure. This has been
challenged by more recent reports suggesting esophageal body dysfunction
to be a better predictor of abnormal acid exposure (39).
Lifestyle modification should be initiated and continued throughout the
course of GERD therapy.
Numerous studies have indicated that elevation of the head of the bed (40,
41), decreased fat intake (42), cessation of smoking (43), and avoiding
recumbency for 3 h postprandially (44) decrease distal esophageal acid
exposure, although data reflecting the true efficacy of these maneuvers in
patients is almost completely lacking. Certain foods [chocolate (45),
alcohol (46), peppermint (47), coffee (48), and perhaps onions and garlic
(49)] have been noted to increase esophageal reflux and should be avoided,
although randomized trials are also not available to test the efficacy of
these maneuvers. Weight loss has been suggested to improve reflux, but
studies have not been able to provide objective evidence of this
association (50). Many authors assume the 20-30% placebo response rate
seen in most randomized trials is due to lifestyle changes, but this has
not been tested. Neither the efficacy nor the potential negative effect of
lifestyle changes on a patient's quality of life have been adequately
examined for any of the maneuvers. Despite this lack of data, expert
opinion holds that education of the patient about factors that may
precipitate reflux is reasonable.
Antacids and over-the-counter acid suppressants are appropriate, initial
patient-directed therapy for GERD. If symptoms persist while on therapy or
warning signs develop (Table 1), the patient should undergo a diagnostic
evaluation (see earlier diagnostic guidelines).
Antacids and antirefluxants such as alginic acid are useful in the
treatment of milder forms of GERD. Antacids (51) and alginic acid (52, 53)
have been shown to be more effective than placebo in the relief of
symptoms induced by a heartburn-promoting meal. In addition, combined
antacid/alginic acid therapy may be superior to antacids alone in the
control of symptoms (54, 55). There are two long-term trials that suggest
effective symptom relief in approximately 20% of patients using
over-the-counter agents (56, 57).
All four of the histamine type-2 receptor antagonists (H2RAs) approved for
use in the United States are now available in an over-the-counter (OTC)
form at a dose that is usually one-half of the standard prescription dose.
These doses have been shown to decrease gastric acid, particularly after a
meal. Though there are some differences in potency, duration, and rapidity
of action, they may generally be used interchangeably. The OTC H2RAs are
particularly useful when taken before an activity that may potentially
result in reflux symptoms (heavy meal or exercise in some patients). Many
patients can predict when they are going to suffer from reflux and can
premedicate with the OTC H2RAs. Famotidine 10 mg taken before an evening
meal has been demonstrated to prevent reflux and restore sleep in patients
who are usually awakened by GERD (58).
Comparisons between OTC H2RAs and antacids are limited. It has been
suggested that antacids provide a more rapid response, but gastric pH
begins to rise less than 30 min after taking a dose of H2RA so this does
not seem to be a major factor. The peak potency of OTC H2RAs and antacids
are similar, but the H2RAs have a much longer duration of action (up to 10
Acid Suppression for GERD
Acid suppression is the mainstay of therapy for GERD. Histamine2-receptor
blockers given in divided doses are effective treatment in many patients.
Proton pump inhibitors provide rapid symptomatic relief and healing of
esophagitis in the highest percentage of patients.
Acid suppression is the mainstay of therapy for GERD. Proton pump
inhibitors provide rapid symptomatic relief and healing of esophagitis in
the highest percentage of patients. Histamine2-receptor blockers given in
divided doses may also be used and are effective treatment in many
patients with less severe GERD.
In the original guideline statement, the results of 33 randomized trials
with more than 3000 patients are presented. Symptomatic relief can be
expected in 27% of placebo-treated, 60% of H2RA-treated, and 83% of
PPI-treated patients. Esophagitis healed in 24% of placebo-treated, 50% of
H2RA-treated, and 78% of proton pump inhibitor-treated patients. We will
not readdress those studies here, but it is clear that whereas some
patients will have relief of symptoms and improvement or healing of
esophagitis with H2RAs, PPIs eliminate symptoms and heal esophagitis more
frequently and more rapidly than the other agents. Both higher doses and
more frequent dosing of H2RAs appear to be more effective in the treatment
of reflux symptoms and healing of esophagitis, but these agents are still
inferior to proton pump inhibitors and more costly at higher dosages (59,
Concerns about the use of PPIs surround the profound decrease in gastric
acid secretion produced by these medications (62). This leads to an
increase in gastrin production from the antral-G cells and sustained
increases in serum gastrin, usually to a mild degree (two to four times
basal) (63). The question of whether these changes in serum gastrin might
produce dangerous trophic effects on the gastric mucosa with long-term use
of PPIs remains to be completely resolved, although both omeprazole and
lanzoprazole are now approved for 1 yr of continuous usage. The experience
with PPIs is approaching a decade in the United States and much longer in
Europe and Australia. There has not been a reported case of gastric
carcinoid type tumor in a patient receiving a PPI, with the exception of
cases who had a multiple endocrine neoplasia syndrome not felt to be
related to the drug. Atrophic gastritis has been reported with long-term
omeprazole therapy. It was recently reported that these patients were
often infected with Helicobacter pylori (64), but the clinical relevance
of these findings has been questioned and essentially discounted (65).
Cobalamin absorption may be decreased with chronic PPI therapy, but no
change in serum levels have been reported after as many as 7 yr of therapy
(66). There has also been no evidence of bacterial overgrowth after
long-term acid suppression (67). It is becoming increasingly clear that
the potential benefit of chronic PPI therapy in patients with chronic or
complicated GERD outweighs any theoretical risk.
There is much debate over the role of H2RAs and PPIs in the initial
treatment of GERD. One approach, the so called step-up therapy, is to
start with a standard or even OTC dose of H2RA and titrate to symptom
control. The other approach, step-down therapy, starts with once- or
perhaps twice-daily proton pump therapy and decreases the therapy to the
lowest form of acid suppression that controls the symptoms. There have
been models constructed to evaluate both the efficacy and
cost-effectiveness of these approaches and neither has been proven
superior, therefore the approach is best left to the choice of the
individual practitioner in consultation with the patient (68, 69).
Promotility Therapy for GERD
Promotility agents such as cisapride and domperidone have an efficacy
similar to standard-dose histamine receptor blockers.
The available promotility agents (cisapride and metoclopramide) have an
efficacy similar to standard-dose histamine receptor blockers.
Defects in esophagogastric motility (LES incompetence, poor esophageal
clearance, and delayed gastric emptying) are central to the pathogenesis
of GERD (70). If these defects could be corrected, then GERD would be
controlled, making suppression of normal amounts of gastric acid
unnecessary. Bethanechol may increase LES pressure to a small degree, but
has limited efficacy in GERD. The frequent central nervous system side
effects of metoclopramide (drowsiness, irritability, extrapyramidal
effects, etc.) have, appropriately, decreased the regular use of this
medication (71). Cisapride (10 mg q.i.d.) can provide effective
symptomatic relief and healing of esophagitis, with results comparable to
cimetidine 400 mg q.i.d. or ranitidine 150 mg b.i.d., and superior to
placebo (72, 73, 74). Combined therapy with cimetidine and either
metoclopramide (10 mg q.i.d.) (75) or cisapride (10 mg q.i.d.) (76) have
been shown to result in improved healing of esophagitis, compared with
cimetidine alone. Cisapride may also be an effective maintenance therapy
for GERD (77, 78). A combination of cisapride and ranitidine was superior
to ranitidine alone in the maintenance therapy of GERD, but inferior to
omeprazole alone (79). Contrary to the positive studies cited,
postprandial reflux as measured with ambulatory pH monitoring was not
decreased in patients treated with cisapride, compared with controls (80).
There have been reports of fatal cardiac dysrhythmias associated with the
combination of cisapride and several agents that are metabolized by the
cytochrome P-450 system (particularly antifungal agents and some
antimicrobials) (81, 82). The widespread use of this medication throughout
the world suggests that these important side effects must be relatively
rare. Although cisapride may be useful in certain patients with a
combination of symptoms (nausea and constipation, among others), PPIs
provide greater control of acid reflux, without the risk, albeit small, of
cardiac rhythm disturbances.
Maintenance Therapy for GERD
Because GERD is a chronic condition, therapy with acid suppression or
promotility agents or both at the lowest dose needed to control symptoms
and prevent complications is appropriate. This may include chronic proton
pump inhibitor therapy.
Because GERD is a chronic condition, continuous therapy to control
symptoms and prevent complications is appropriate. Chronic proton pump
inhibitor therapy is an effective and appropriate form of maintenance
therapy in many patients.
Many, perhaps most, patients with GERD require long-term, possibly
life-long, therapy. Therefore, maintenance therapy becomes a major
concern. Effective maintenance therapy should keep the patient's symptoms
comfortably under control and prevent complications. This will vary in
each patient and may require only antacids and lifestyle modifications in
as many as 20% of patients. Other patients with chronic reflux (50%) have
frequent symptomatic relapses despite appropriate therapy. Patients whose
disease has been controlled with PPIs often will have symptomatic relapses
and failure of healing of esophagitis with a standard dose, or even
higher-dose H2RA or prokinetic therapy (83). A full dose of H2RA given
once daily, although effective for peptic ulcer disease, is not
appropriate for GERD. Reduced doses of PPIs have not been shown
consistently to be effective long-term in the therapy of GERD. This
includes alternate-day omeprazole (84) or so-called weekend therapy (85).
A daily dose of 10 mg may be superior to standard-dose ranitidine (86).
The frequent marked improvement in GERD symptoms noted with the acid
suppression produced by full-dose PPI is usually followed by a rapid
return of symptoms once it is discontinued (87).
There are clear data that acid suppression decreases the recurrence of
peptic esophageal strictures. Cimetidine 400 mg four times a day did not
affect the frequency of the need for dilation (88), but several studies
have found that full-dose PPIs will lengthen the interval between
symptomatic relapses (89, 90). There are no similar data in regards to the
prevention or prevention of progression of Barrett's esophagus. It does
not appear that Barrett's esophagus will regress with either medical or
surgical therapy (91, 92). There have been reports of occasional islands
of squamous epithelium appearing with chronic PPI therapy, but the
significance of this is not known (93). Abnormalities of esophageal
peristalsis have long been thought to predispose to reflux, but recent
studies suggest that at least a portion of these motility disorders are in
fact a consequence of the reflux and may improve while taking antireflux
Surgical Therapy for GERD
Surgery should be considered if medical therapy fails or is deemed
appropriate in individual cases.
Antireflux surgery, performed by an experienced surgeon, is a maintenance
option for the patient with well-documented GERD.
Considerable controversy exists over the long-term effectiveness of
surgical intervention in GERD and whether it is superior to chronic
medical therapy. In the two published trials of medical versus surgical
therapy, surgery has been shown to be more effective. The initial
comparison favored surgical over a rather modest medical therapy
(essentially antacids and lifestyle changes) over a 36-month period (95).
A comparison of surgery versus ranitidine and metoclopramide indicated
superiority for the surgical approach (96). Preliminary results of a
similar comparison between surgery and PPIs were recently presented. This
randomized trial of 310 patients, who initially had their disease
controlled with omeprazole 40 mg per day, found surgery to be slightly
superior (maintenance of esophagitis healing and symptoms) to omeprazole
20 mg per day at the end of 3 yr (97). If dose titration up to 40-60 mg
per day of omeprazole was used the two treatments were equal. Proper
selection and preoperative evaluation of patients is very important. If
typical reflux esophagitis is not present endoscopically, ambulatory pH
testing should be performed. Esophageal manometry may alter the surgical
decision in as many as 10% and should be a routine procedure before
antireflux surgery. Delayed gastric emptying has been reported to increase
the rate of complication after an antireflux surgery, but the utility of
the routine preoperative use of these tests is not clear (98).
The medical therapy of GERD has focused on the neutralization of refluxed
acid from the stomach. It is clear that there are other injurious factors
involved. The possibility of duodenogastroesophageal reflux (alkaline
reflux) has been raised as an additional indication for the surgical
repair of the LES in patients with GERD (99). Although it appears that
control of acid decreases the injury in patients who reflux duodenal
contents (100, 101), certain of these patients may benefit from antireflux
surgery although objective evidence of this type of reflux is difficult to
A laparoscopic approach to antireflux surgery is rapidly evolving and
appears to be equal or perhaps even superior to the open approach (102,
103, 104). A recent study found significantly lower cost and shorter
lengths of hospital stay with the laparoscopic approach, although patient
satisfaction was similar between the open and laparoscopic groups (105).
This approach may not be possible in some patients who have had previous
surgery and in the very obese. The decreased postoperative morbidity
involved in this approach should not change the indications or evaluations
for surgery, but does make this option more attractive for some patients
whose alternative would be long-term medical therapy (106). The long-term
durability of laparoscopic antireflux surgery remains incompletely
defined, but several studies of the open technique have reported adequate
control of disease for as long as 20 yr (107, 108). Another study
suggested a deterioration in both LES pressure and endoscopic histology
back toward the presurgical level 5-6 yr postoperatively (109).
GERD Refractory to Therapy
GERD refractory to medical therapy is very rare. The diagnosis should be
carefully confirmed before chronic high-dose acid suppression or
The vast majority of patients will have their symptoms and mucosal disease
controlled with medical therapy for GERD. When a patient presents with
either typical or atypical symptoms of GERD refractory to therapy, the
diagnosis, current therapy, or both should be reconsidered. This may
involve an ambulatory pH study, either with or without therapy, additional
endoscopic and manometric evaluations, and consideration of testing and
therapeutic trials for other conditions that may produce symptoms similar
to GERD. Although PPIs provide outstanding acid control in the vast
majority of patients, there has been a recent report of two patients who
had refractory reflux (by pH study and symptoms) while taking omeprazole,
who had better acid suppression with high-dose H2-receptor therapy (110).
These cases are rare, but emphasize the need for individualized therapy
and testing when symptoms consistent with GERD are refractory to therapy.
Extraesophageal Manifestations of GERD
GERD should be considered in the differential diagnosis of unexplained
cases of chronic chest pain, cough, hoarseness, and asthma.
Several other symptoms may be related to GERD and are usually referred to
as atypical or extraesophageal symptoms of GERD. An association with GERD
may occur in as many as 50% of patients with noncardiac chest pain (111),
78% of patients with chronic hoarseness (112), and 82% of patients with
asthma (113). Chronic cough has also been associated with GERD (114, 115).
Gastroesophageal reflux may be induced by exercise and can either be
asymptomatic or present with typical or atypical symptoms (116, 117).
Dental erosions have been associated with asymptomatic gastroesophageal
reflux as well (118). These patients may or may not have typical symptoms
of GERD and are often best diagnosed with either an empirical trial of
therapy, ambulatory pH testing, or, in some cases, both. It has been
suggested that these patients may require higher doses of acid suppression
and longer therapeutic trials than patients with more typical symptoms of
GERD. Finally, when these symptoms are refractory to medical therapy, the
diagnosis of GERD needs to be carefully reconsidered before recommending
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