Guidelines for Clinical Care

Quality Department Ambulatory

GERD Gastroesophageal Reflux Disease (GERD)

Guideline Team
Team Leader Patient population: Adults
Joel J Heidelbaugh, MD Objective: To implement a cost-effective and evidence-based strategy for the diagnosis and
Family Medicine treatment of gastroesophageal reflux disease (GERD).
Team Members
Key Points:
R Van Harrison, PhD
 Diagnosis
Learning Health Sciences
Mark A McQuillan, MD History. If classic symptoms of heartburn and acid regurgitation dominate a patient’s history, then
General Medicine they can help establish the diagnosis of GERD with sufficiently high specificity, although sensitivity
Timothy T Nostrant, MD remains low compared to 24-hour pH monitoring. The presence of atypical symptoms (Table 1),
Gastroenterology although common, cannot sufficiently support the clinical diagnosis of GERD [B*].
Testing. No gold standard exists for the diagnosis of GERD [A*]. Although 24-hour pH monitoring
Initial Release is accepted as the standard with a sensitivity of 85% and specificity of 95%, false positives and false
March 2002 negatives still exist [II B*]. Endoscopy lacks sensitivity in determining pathologic reflux but can
Most Recent Major Update identify complications (eg, strictures, erosive esophagitis, Barrett’s esophagus) [I A]. Barium
May 2012 radiography has limited usefulness in the diagnosis of GERD and is not recommended [III B*].
Content Reviewed Therapeutic trial. An empiric trial of anti-secretory therapy can identify patients with GERD who
March 2018 lack alarm or warning symptoms (Table 2) [I A*] and may be helpful in the evaluation of those with
atypical manifestations of GERD, specifically non-cardiac chest pain [II B*].
 Treatment
Ambulatory Clinical Lifestyle modifications. Lifestyle modifications (Table 3) should be recommended throughout the
Guidelines Oversight
treatment of GERD [II B], yet there is evidence-based data to support only weight loss and avoiding
Karl T Rew, MD recumbency several hours after meals [II C*].
R Van Harrison, PhD
Pharmacologic treatment. H2-receptor antagonists (H2RAs), proton pump inhibitors (PPIs), and
prokinetics have proven efficacy in the treatment of GERD [I A*]. Prokinetics are as effective as
H2RAs but are currently unavailable [III A*]. Carafate and antacids are ineffective [III A*], but may
Literature search service
Taubman Health Sciences
be used as supplemental acid-neutralizing agents for certain patients with GERD [II D*].
Library  Non-erosive reflux disease (NERD): Step-up (H2RA, then a PPI if no improvement) and step-down
(PPI, then the lowest dose of acid suppression) therapy are equally effective for acute treatment
and maintenance [I B*]. On demand (patient-directed) therapy is the most cost-effective [I B].
For more information  Erosive esophagitis: Initial PPI therapy is the treatment of choice for acute and maintenance therapy
734-936-9771
for patients with documented erosive esophagitis [I A*].
www.uofmhealth.org/provide  Take PPIs 30-60 minutes prior to breakfast (and also dinner if taking twice daily) to optimize
r/clinical-care-guidelines effectiveness [I B*]. Use generic and OTC formulations exclusively, eliminating need for prior
authorizations.
© Regents of the
University of Michigan  Patients should not be left on anti-secretory therapy without re-evaluation of symptoms to minimize
cost and the potential adverse events from medications [I B].
Surgery. Anti-reflux surgery is an alternative modality in GERD treatment for patients with chronic
These guidelines should not be reflux and recalcitrant symptoms [II A*], yet has a significant complication rate (10-20%).
construed as including all Resumption of pre-operative medication treatment is common (> 50%) and may increase over time.
proper methods of care or
excluding other acceptable Other endoscopic treatments. While less invasive and with fewer complications, they have lower
methods of care reasonably response rates than anti-reflux surgery [II C*], and have not been shown to reduce acid exposure.
directed to obtaining the same
results. The ultimate judgment  Follow up
regarding any specific clinical
procedure or treatment must be
Symptoms unchanged. If symptoms remain unchanged in a patient with a prior normal endoscopy,
made by the physician in light repeating endoscopy has no benefit and is not recommended [III C*].
of the circumstances presented
by the patient.
Warning signs. Patients with warning or alarm signs and symptoms suggesting complications from
GERD (Table 2) should be referred to a GERD specialist.
Risk for complications. Further diagnostic testing (eg, EGD [esophagogastroduodenoscopy], 24-
hour pH monitoring) should be considered in patients who do not respond to acid suppression therapy
[I C*] and in patients with a chronic history of GERD who are at risk for complications. Chronic
reflux has been suspected to play a major role in the development of Barrett’s esophagus, yet it is
unknown if outcomes can be improved through surveillance and medical treatment [D*].
* Strength of recommendation:
I = generally should be performed; II = may be reasonable to perform; III = generally should not be performed.
Level of evidence supporting a diagnostic method or an intervention:
A=randomized controlled trials; B=controlled trials, no randomization; C=observational trials; D=opinion of expert panel.
1
 Figure 1. Diagnosis and Treatment of GERD

Table 1. Atypical Table 2. Alarm or Warning

Table 3. Lifestyle Modifications
Signs of GERD Signs Suggesting Complicated
GERD
Chronic cough Elevate head of bed 6-8 inches
Asthma Dysphagia Decrease fatty meals
Recurrent sore throat Odynophagia Stop smoking
Recurrent laryngitis GI bleeding Avoid recumbency or sleeping for 3-4 hours after
eating
Dental enamel loss Iron deficiency anemia Avoid certain foods: chocolate, alcohol, peppermint,
caffeinated coffee and other beverages, onions,
garlic, fatty foods, citrus, tomato
Subglottic stenosis Weight loss
Globus sensation Early satiety Avoid large meals
Chest pain Vomiting Weight loss
Onset of symptoms at
age > 50 Avoid medications that can potentiate symptoms:
calcium channel blockers, beta-agonists, alpha-
adrenergic agonists, theophylline, nitrates, and
some sedatives (benzodiazepines).

2 UMHS GERD Guideline, September, 2013

 Table 4. Medications for Acute Treatment and Maintenance Regimens
Drug Dose Equivalents a Dosage b OTC Generic c Brand c
H2 receptor antagonists
cimetidine (Tagamet HB) 200 mg twice daily 200 mg twice daily $25 $25 NA
cimetidine (Tagamet) 400 mg twice daily 400 mg twice daily $12 $25 NA
famotidine (Pepcid) 20 mg twice daily 20 mg twice daily $11 $9 $655
nizatidine (Axid) 150 mg twice daily 150 mg twice daily $43 $37 NA
ranitidine (Zantac 150) 150 mg twice daily 150 mg twice daily $20 $9 $391
ranitidine (Zantac 300) 300 mg nightly 300 mg nightly $20 $14 $354

Proton pump inhibitors

dexlansoprazole (Dexilant) 30 mg daily 30 mg once daily NA NA $296
esomeprazole (Nexium) 20 mg daily 20 to 40 mg daily $25-34 $22-27 $271
lansoprazole (Prevacid) 30 mg daily 15 or 30 mg daily before breakfast $15-29 $15-24 $448
omeprazole (Prilosec) 20 mg daily 20 or 40 mg daily before breakfast $15-30 $5-8 NA
pantoprazole (Protonix) 40 mg daily 40 mg daily before breakfast NA $6 $465
rabeprazole (Aciphex) 20 mg daily 20 mg daily before breakfast NA $21 $567
a For each drug, the dose listed in this column has an effect similar to the doses listed in this column for other drugs.
b Maximum GERD dose for PPIs except dexlansoprazole is the highest listed dose amount, but given twice daily before breakfast and before
dinner. Dexlansoprazole maximum dose is 60 mg once daily.
c Cost = For brand drugs, Average Wholesale Price minus 10%. AWP from Red Book Online 4/3/18. For generic drugs, Maximum Allowable

Cost plus $3 from BCBS of Michigan MAC List, 4/1/18. Prices calculated for 30-day supply unless otherwise noted.

Clinical Background
Clinical Problem endoscopic evidence of disease. Although these diagnostic
limitations occur less often when patients present with the
Incidence classic symptoms of heartburn and acid regurgitation,
diagnosis may be difficult in patients with recalcitrant
Gastroesophageal reflux disease (GERD) is a common courses and extraesophageal manifestations of this disease.
chronic, relapsing condition that carries a risk of significant
morbidity and potential mortality from resultant Diagnostic Problems
complications. While many patients self-diagnose, self-treat
and do not seek medical attention for their symptoms, others The lack of a gold standard in the diagnosis of GERD
suffer from more severe disease with esophageal damage presents a clinical dilemma in treating patients with reflux
ranging from erosive to ulcerative esophagitis. symptomatology. Many related syndromes including
dyspepsia, atypical GERD, H. pylori-induced gastritis,
More than 60 million adult Americans suffer from heartburn peptic ulcer disease and gastric cancer may present similarly,
at least once a month, and over 25 million experience making accurate history taking important. The most common
heartburn daily. The National Ambulatory Medical Care referral to a gastroenterologist from primary care is for
Survey (NAMCS) found that 38.53 million annual adult evaluation of refractory GERD. Even in these cases the pre-
outpatient visits were related to GERD. For patients test sensitivity and specificity for accurate diagnosis remain
presenting with GERD symptoms, 40-60% or more have low. Invasive testing is over-utilized and not always cost-
reflux esophagitis. Up to 10% of these patients will have effective, given the relatively small risk of misdiagnosis
erosive esophagitis on upper endoscopy. GERD is more based upon an accurate patient history. Empiric
prevalent in pregnant women, and a higher complication rate pharmacotherapy is advantageous based on both cost and
exists among the elderly. Patients with GERD generally convenience for the patient.
report decreases in productivity, quality of life and overall
well-being. Many patients rate their quality of life to be lower Treatment Decision Problems
than that reported by patients with untreated angina pectoris
or chronic heart failure. GERD is a risk factor for the Although empiric anti-secretory therapy with a histamine-2
development of esophageal adenocarcinoma, further receptor antagonist (H2RA) or a proton pump inhibitor (PPI)
increasing the importance of its diagnosis and treatment. provides symptomatic relief from heartburn and
regurgitation in most cases, the potential long-term adverse
Extraesophageal manifestations associated with GERD effects of anti-reflux medications are unknown. No cases of
occur in up to 50% of patients with non-cardiac chest pain, gastric cancer or carcinoid linked to use of the PPIs have
78% of patients with chronic hoarseness, and 82% of patients been reported since the advent of this class of medication
with asthma. Over 50% of patients with GERD have no over 20 years ago.
3 UMHS GERD Guideline, September, 2013
 stricture or adenocarcinoma of the esophagus are very rare
Complications from GERD (eg, Barrett’s esophagus, unless the initial endoscopy shows esophagitis or Barrett’s
adenocarcinoma of the esophagus) are rare but do exist; 10- esophagus. A normal endoscopy with symptomatic GERD
15% with GERD will develop Barrett’s esophagus, and 1- presents a good prognosis, and does not need to be repeated
10% of those with Barrett’s will develop adenocarcinoma for 10 years unless alarm or warning symptoms are present
over 10-20 years. Chronic reflux has been suspected to play (Table 2). Long-term natural history studies are limited.
a major role in the development of Barrett’s esophagus
(specialized columnar epithelium or intestinal metaplasia), Diagnosis
yet it is unknown if outcomes can be improved through
surveillance and medical treatment. anti-secretory therapy Evidence-based limitations exist when trying to assess the
has been shown to reduce the need for recurrent dilation from validity of the diagnostic modalities for GERD. Most studies
esophageal stricture formation. have flawed methods because no gold standard exists.
However, the calculated numbers are helpful in providing a
Previous cost-effectiveness models for endoscopic screening framework to assess available options. Recent studies
were flawed in that certain studies examined only patients suggest that combining diagnostic modalities (omeprazole
with erosive esophagitis and excluded patients with non- challenge test [daily omeprazole for two weeks], 24-hour pH
erosive esophagitis (NERD), while some studies included monitoring, and endoscopy) may increase the sensitivity for
data on anti-reflux surgery only for patients who failed diagnosis of GERD (approaching 100%), but this approach
medical therapy. These studies also viewed a short-term is not practical in the routine clinical setting.
analysis of therapeutic efficacy, rather than following
patients over a lifetime, and did not allow for the switching 24-hour pH monitoring offers adequate sensitivity and
from one particular medication to another. specificity in establishing a diagnosis of GERD in cases that
do not readily respond to anti-secretory therapy. It can also
help with patient compliance by establishing that acid
Rationale for Recommendations production has been eliminated or reduced to zero. The
UMHS approach to 24-hour pH monitoring includes:
Etiology scheduling, availability, report turnaround time, patient
satisfaction, cost, and insurance coverage.
Most patients with GERD have normal baseline lower
esophageal sphincter tone. The most common mechanism for History. Since GERD occurs with few if any abnormal
acid reflux is transient relaxation of the lower esophageal physical findings, a well-taken history is essential in
sphincter (≥ 90% of reflux episodes in normal subjects and establishing the diagnosis of GERD. Symptoms of classic
75% of episodes in patients with symptomatic GERD). Other burning in the chest, with sour or bitter taste, and acid
mechanisms include breaching the lower esophageal regurgitation have been shown to correctly identify GERD
sphincter because of increased intra-abdominal pressure with a sensitivity of 89% and specificity of 94%. Up to 1/3
(strain induced reflux) and a baseline low pressure at the of patients with GERD will not report the classic symptoms
lower esophageal sphincter. The latter two mechanisms of heartburn and regurgitation. However, symptom
increase in frequency with greater reflux severity. Other frequency, duration and severity are equally distributed
factors include delayed gastric emptying (co-factor in 20% among patients with varying grades of esophagitis and
of GERD patients), medication use (particularly calcium Barrett’s esophagus and cannot be used reliably to diagnose
channel blockers), hiatal hernia (increased strain induced complications of GERD. There may also be some symptom
reflux and poor acid clearance from hernia sac), and poor overlap with other conditions (non-cardiac chest pain, cough,
esophageal acid clearance (eg, esophageal dysmotility, etc.).
scleroderma, decreased salivary production).
PPI diagnostic test. A favorable symptomatic response to a
short course of a PPI (once daily for two weeks) is considered
Natural History
to support a diagnosis of GERD when symptoms of non-
cardiac chest pain are present. A meta-analysis found that a
Most GERD patients (80-90%) do not seek medical attention successful short-term trial of PPI therapy did not confidently
and will self-medicate with OTC anti-secretory therapy establish a diagnosis of GERD (sensitivity 78%, specificity
(50%). In patients seeing physicians, most will have chronic 54%) when 24-hour pH monitoring was used as the reference
symptoms that will occur off treatment. Patients with more standard. This may be due to an observed clinical benefit of
severe esophagitis will have symptoms recur more quickly PPIs in treating other acid-related conditions (as seen in the
and almost all will have recurrent symptoms and esophagitis heterogeneous dyspeptic population), patients with enhanced
if followed up for ≥ 1 year. Progression of disease can be esophageal sensitivity to acid (without true GERD), or even
seen in up to 25% of patients with esophagitis, but it is less due to a placebo effect. In those with non-cardiac chest pain,
likely to occur if esophagitis is not present or is mild. (Using an empiric trial of high-dose omeprazole (40 mg AM, 20 mg
the Los Angeles Classification for Gastroesophageal Reflux PM) had a sensitivity of 78% and specificity of 85%.
Disease, this would be LA grade A or B.) Complications Standard dosages may have lower sensitivity and specificity.
such as Barrett’s esophagus, esophageal ulcers, esophageal

4 UMHS GERD Guideline, September, 2013

Empiric or therapeutic trial. Diagnostic modalities cannot of complications (eg, Barrett’s esophagus, cancer) but
reliably exclude GERD even if they are negative. Therefore, troublesome dysphagia and weight loss are predictive of
an empiric trial of anti-secretory therapy may be the most complications. Endoscopy should be done for patients not
expeditious way in which to diagnose GERD in those with responding to a twice-daily PPI.
classic symptoms and who do not have symptoms suggestive
of complications (eg, carcinoma, stricture). (See discussion Endoscopic biopsies are indicated to detect Barrett’s
of "step-up" therapy and "step-down" therapy in treatment esophagus and eosinophilic esophagitis, but are not indicated
section.) when the endoscopy is normal. Random biopsies and
directed biopsies to nodular areas should be done if Barrett’s
Empiric therapy should be tried for two weeks for patients esophagus is seen or eosinophilic esophagitis is suspected.
with typical GERD symptoms. Treatment can be initiated
with standard dosage of either an H2RA twice daily (on Routine endoscopy in the general population is not indicated.
demand, taken when symptoms occur) or a PPI (30-60 High-risk patients for esophageal adenocarcinoma such as
minutes prior to first meal of the day), with drug selection age ≥ 50, males, chronic GERD, hiatal hernia, high body
depending on clinical presentation and appropriate cost- mass index, central obesity, and tobacco use, may warrant
effectiveness and the end point of complete symptom relief. endoscopy.
(See Figure 1 and costs in Table 4). If symptom relief is not
adequate and H2RA twice daily was initially used, then PPI Esophageal manometry. Esophageal manometry should be
daily should be used. If PPI daily was initially used, then second line for diagnosis of GERD. Detection of achalasia,
increase to maximum dose PPI daily or twice daily (30-60 spastic achalasia, or distal esophageal spasm is critical if
minutes prior to first and last meals). patient is having antireflux surgery. Adequate peristalsis is
another prerequisite for anti-reflux surgery. Esophageal
For patients who initially present with more severe and more manometry is not indicated for the detection of GERD. High
frequent symptoms of typical GERD, treatment may be resolution manometry is superior to standard manometry in
initiated with higher and more frequent dosages of an H2RA the detection of major motility disorders mimicking GERD.
or PPI. If symptom relief is not adequate from the initial dose
(see Figure 1), then increase potency or frequency as needed Other Testing for GERD. Esophageal acid
to obtain complete symptom relief: high-dose H2RA to PPI perfusion testing (also called Bernstein testing), esophageal
daily, PPI daily or maximum dose PPI daily or twice daily. sensory testing, and barium esophagram are not indicated for
If there is no response when using maximal doses and the diagnosis of GERD. Barium esophagram may be helpful
frequencies, then diagnostic testing should be performed in the preoperative phase of anti-reflux surgery or in the
after 8 weeks of therapy. evaluation of major motor disorders (eg, achalasia, diffuse
esophageal spasm) after a normal endoscopy.
If the patient responds with symptom relief, give 8-12 weeks
of therapy, ie, enough to heal undiagnosed esophagitis. If the Treatment
patient has complete symptom relief at 8-12 weeks, taper
over 1 month to lowest effective dose of the medication that Lifestyle modifications. For patients with a history typical
gives complete relief, eg, H2RA on demand, PPI every other for uncomplicated GERD, expert opinion is to discuss and
day. If symptoms recur, put patient back on the lowest offer various lifestyle modifications throughout the course of
effective medication and dose, and consider further testing GERD therapy (see Table 3). Neither the efficacy nor the
depending on clinical presentation and course. potential negative effects of lifestyle changes on a patient’s
quality of life have been adequately examined. With
Patients who present with atypical or extraesophageal relatively little data available, it is reasonable to educate
manifestations take a longer time to respond to empiric patients about factors that may precipitate reflux. Only
therapy, and often require twice-daily dosing. If there is no recently has there been evidence to support weight loss and
improvement at all in symptoms after two months, further avoiding recumbency in favorable outcomes.
testing should be pursued.
Head elevation. Numerous studies have indicated that
Endoscopy and biopsy in GERD. Endoscopy is used to elevating the head of a patient’s bed by 4 to 8 inches, as well
detect mucosal injury, esophageal stricture, Barrett’s as avoiding recumbency for 3 hours or greater after a large
esophagus or esophageal cancer. Eosinophilic esophagitis, or fatty meal, may decrease distal esophageal acid exposure.
diagnosed by mucosal changes and biopsies (at least 5 in However, data reflecting the true efficacy of this maneuver
proximal and distal esophagus), is increasingly important. in patient reported outcomes is lacking. It has also been
Mucosal injury is seen in less than 50% of patients with suggested that patients should avoid sleeping on additional
GERD symptoms, and therefore the diagnostic sensitivity is pillows, as this may increase abdominal pressure and lead to
less than 50%, but specificity is 95%. increased reflux.

Esophagitis is best defined by the Los Angeles Classification Avoid certain foods. Several foods are believed to be
of Gastroesophageal Reflux Disease (LA grades A through direct esophageal irritants: citrus juices, carbonated
D). Alarm signs and severity of symptoms are not predictive beverages, coffee and caffeine, chocolate, spicy foods, fatty
5 UMHS GERD Guideline, September, 2013
foods, or late evening meals. However, no randomized when they will suffer reflux symptomatology and may
controlled trials are available to support recommendations to benefit from premedication with these OTC H2RAs. The
avoid or minimize these foods. Individualized dietary OTC H2RAs are believed to be superior in efficacy when
modification trials may be reasonable to help elucidate compared to antacids, alginic acid, and placebo.
potential causative dietary factors.
Numerous randomized controlled trials have demonstrated
Weight loss. A direct association among weight, reflux, that standard dose H2RAs are more effective than placebo at
and reflux complications has been demonstrated. Weight loss relieving heartburn in cases of GERD, with symptomatic
has been shown to improve global symptom scores, relief reported in 60% of cases. A systematic review found
particularly if weight gain occurred before the onset of that people in trials on H2RAs had faster healing rates than
GERD symptoms. people in trials on placebo: over a 4-8 week period a healed
esophagitis rate of 50% on H2RA and 24% on placebo.
Smoking cessation and alcohol minimization. Smoking
cessation and the elimination or minimization of alcohol are Both higher doses and more frequent dosing of H2RAs
also encouraged for a variety of health reasons. Both nicotine appear to be more effective in the treatment of reflux
and alcohol have been shown to decrease lower esophageal symptoms and healing of esophagitis. If the patient is on
sphincter pressure and lead to further esophageal irritation. maximal therapy, the disadvantages include cost and
A systematic review found that smoking was associated with compliance. Some patients will develop tolerance to the
an increase in GERD symptoms (over 1-2 days); yet smoking H2RAs, with decreased efficacy observed after 30 days of
cessation was not shown to decrease GERD symptoms in 3 treatment.
low-quality studies. Alcohol use may or may not be
associated with reflux symptoms. Most evidence describing adverse effects is from case reports
or uncontrolled trials. H2RAs have been associated with rare
Avoid medications that decrease lower esophageal cytopenias, gynecomastia, liver function test abnormalities,
pressure or irritate the esophagus. Medications that decrease and hypersensitivity reactions. In the long-term, there have
lower esophageal sphincter pressure should be avoided in been no controlled trials with follow-up on the safety of
patients with symptoms of GERD. These medications chronic use of H2RAs. Cimetidine may cause gynecomastia
include calcium channel blockers, beta-agonists, alpha- or antiandrogenic side effects, and may interact with
adrenergic agonists, theophylline, nitrates, PDE-5 inhibitors medications metabolized by cytochrome P450.
(eg, avanafil, sildenafil, tadalafil, vardenafil),
anticholinergics, narcotics, and some sedatives Proton Pump Inhibitors (PPIs). Several studies have
(benzodiazepines). Medications that irritate the esophagus demonstrated that on-demand therapy with PPIs is the most
include NSAIDS, ferrous sulfate, and bisphosphonates. cost-effective method for non-erosive reflux disease
(NERD). Evidence from numerous randomized controlled
Avoid tight clothing around waist. Another anecdotal trials has shown that PPIs are more effective than both
suggestion is that patients refrain from wearing tight clothing H2RAs and placebo in controlling symptoms from erosive
around the waist to minimize strain-induced reflux. reflux disease (83% compared to 60% and 27%,
respectively) over a 4-8 week period. One systematic review
Over-the-counter (OTC) remedies. Antacids and OTC compared the efficacy of PPIs and H2RAs and found that a
anti-secretory therapy (H2RAs, PPIs) are appropriate initial greater number of people improved symptomatically with
patient-directed therapy for GERD. Antacids (Tums, PPIs, yet the difference was not significant for heartburn
Rolaids, Maalox) and combined antacid with alginic acid remission. One randomized controlled trial showed that at 12
(Gaviscon) have been shown to be more effective than months, significantly more people were still in remission
placebo in the relief of daytime GERD symptoms. Two long- with omeprazole compared to ranitidine. Another
term studies suggest that approximately 20% of patients randomized controlled trial found that treatment with
experience some relief from over-the-counter agents. omeprazole was more likely than ranitidine to improve
symptom and psychological well-being scores.
H2 receptor antagonists (H2RAs). All four of the
histamine type-2 receptor antagonists (H2RAs: cimetidine, In the treatment of erosive esophagitis, PPIs had faster
famotidine, nizatidine, and ranitidine) have been approved healing rates than either H2RAs or placebo (78% compared
for use in the US as OTC preparations at a dose that is to 50% and 24%, respectively) over a 4-8 week period. No
uniformly one-half of the standard lowest prescription randomized controlled trials have examined therapy for a
dosage for each compound; ranitidine is now available in an longer period of time.
OTC formulation at standard dose. At these dosages, the
H2RAs decrease gastric acid production, particularly after One randomized controlled trial found no evidence of a
eating a meal, without affecting esophagogastric barrier significant difference among four PPIs, including
dysfunction. The four H2RAs are virtually interchangeable lansoprazole, omeprazole, pantoprazole, and rabeprazole in
at these dosages, with similarities in the rapidity and duration the healing of erosive esophagitis. Efficacy in pH changes
of action. The OTC costs are equivalent (although the was not studied. The least expensive PPIs are omeprazole
generic costs differ by dosage). Some patients may predict and lansoprazole, which are available generically and OTC.
6 UMHS GERD Guideline, September, 2013
A single study showed that esomeprazole, the S-isomer of Surgical treatment. Anti-reflux surgery is an accepted
omeprazole, at doses of 20 mg and 40 mg is more effective alternative treatment for symptomatic reflux of acid or bile
than omeprazole 20 mg in both healing and symptom in certain patients. The basic tenets of surgery are reduction
resolution in GERD patients with reflux esophagitis, with a of the hiatal hernia, repair of the diaphragmatic hiatus,
tolerability profile comparable to that of omeprazole. A strengthening the attachment between the gastroesophageal
randomized controlled trial compared esomeprazole 40 mg junction and the posterior diaphragm, and strengthening the
to lansoprazole 30 mg. Esomeprazole was superior in healing anti-reflux barrier by adding a gastric wrap around the
and symptom control, with superiority highest in more gastroesophageal junction (fundoplication). Controlled trials
severe degrees of esophagitis. comparing open and laparoscopic approaches have shown
similar efficacy and complications, with lower morbidity and
The potential benefit of chronic PPI therapy in patients with shorter hospital stays in the laparoscopic repair group.
chronic or complicated GERD generally outweighs any
theoretical risk of adverse events. Risks associated with Post-surgical complications are common, but they are
chronic PPI therapy include Clostridium-difficile-associated typically short term and manageable in most instances.
diarrhea (adjusted odds ratio [AOR] = 2.1 – 2.6); Short-term solid food dysphagia occurs in 10% of patients
community-acquired pneumonia (AOR = 1.5 – 1.9); bone (2-3% have permanent symptoms) and gas bloating occurs in
fracture (AOR = 1.4 – 1.6); vitamin B12 deficiency (AOR = 7-10% of patients. Diarrhea, nausea, and early satiety occur
1.0 – 4.46); antiplatelet interactions (AOR = 1.25). Data more rarely. While some complication occurs in up to 20%
regarding risks of bone fracture and antiplatelet interactions of patients, major complications occur in only 3-4% of
are controversial. A 2011 FDA warning recommends patients. Patient satisfaction is high when GERD symptoms
periodic surveillance of serum magnesium levels due to are well controlled.
potential hypomagnesemia.
Controlled trials comparing anti-reflux surgery to antacids,
Since all data were collected retrospectively, a definitive H2RAs and PPIs have shown marginal superiority to
cause-and-effect relationship cannot be proven. All patients surgery. Studies comparing surgery with proton pump
on long-term PPI therapy should be re-evaluated periodically inhibitors have shown similar efficacy if PPI could be titrated
to determine need and to weigh potential risks versus to response. Long-term follow-up trials have shown that 52%
benefits of therapy. of patients are back on anti-reflux medications 3-5 years after
surgery, most likely secondary to a combination of poor
Baclofen patient selection and surgical breakdown.

While not considered to be first-line therapy, baclofen has The choice to consider anti-reflux surgery must be
been shown to offer symptomatic relief for patients with individualized. Patients should have documented acid reflux,
GERD. This approach is aimed at decreasing the number of a defective anti-reflux barrier in the absence of poor gastric
transient lower esophageal sphincter relaxations and emptying, normal esophagus motility and at least a partial
increasing lower esophageal sphincter tone. These effects response to acid reduction therapy. Surgery appears to be
have been observed most significantly after eating a meal. most effective for heartburn and regurgitation (75-90%) and
less effective for extraesophageal symptoms (50-75%).
Prokinetics
Other endoscopic treatments for GERD. Radiofrequency
Previous prokinetic medications (eg, cisapride) were taken heating of the GE junction (Stretta), endoscopic gastroplasty
off the US market several years ago due to increased (Bard, Wilson Cook), polymer injections and full thickness
cardiovascular risks. Mosapride, a newer generation gastroplication have been shown to improve quality of life in
prokinetic not currently available in the US, has been shown sham controlled trials. Duration of effect and acid control are
to improve reflux symptoms and gastric emptying when less than surgical fundoplication (30-50% compared to >
combined with omeprazole. 70% at three years). Most of the commercial products for
endoscopic anti-reflux treatments have been removed from
Alternative Therapies the market mainly for non-coverage by insurance companies.

No randomized controlled trials have been conducted to date Treatment Failure

to compare treatment outcomes between conventional anti-
secretory therapy and alternative therapies. Use of Empiric treatment should be limited; if no response is seen
demulcents (eg, licorice root, marshmallow), ginseng, and after 8 weeks of anti-secretory therapy, consider referring the
apple cider vinegar have shown varying degrees of patient for upper endoscopy. Treatment response should be
symptomatic improvement in small numbers of patients. present in 2-4 weeks for patients with typical symptoms.
Acupuncture may also have some benefit, as one trial found Patients with atypical symptoms also have an initial response
this modality to be more effective than doubling the dose of in one month, but may require 3-6 months for maximal
a PPI in patients with non-erosive disease. response. Patients with atypical symptoms may require
higher PPI doses for response.

7 UMHS GERD Guideline, September, 2013

Empiric treatment in patients with atypical symptoms is Step-down therapy. Once symptoms are controlled after
appropriate if typical symptoms are also present. 24-hour step-up therapy, step-down therapy commences with the
esophageal pH monitoring off of anti-reflux medications patient taking a PPI for 8 weeks, followed by an H2RA if
might be the best diagnostic approach initially in patients GERD symptoms were adequately controlled with a PPI,
with atypical symptoms only since ≤ 30% of patients will then stepping down further to on-demand use of antacids if
have GERD associated symptoms. If patients with atypical the patient was asymptomatic while taking an H2RA. The
symptoms do not respond to treatment in 1-3 months, then majority of patients who take more than a single daily dose
GERD is not likely the cause and the other diagnoses should of a PPI and who experience relief of symptoms can be
be entertained. successfully stepped down to single-dose therapy without a
recurrence of reflux symptoms. However, a small percentage
Maintenance Regimens of patients with refractory GERD will need long-term
therapy with higher doses of a PPI to control symptoms.
The goal of maintenance anti-secretory therapy is to have a
symptom-free individual without esophagitis. Multiple On demand therapy. Treatment can be initiated with
regimens are used to accomplish this. Increasing severity of standard dosage of either a PPI daily or an H2RA twice daily
esophagitis is associated with increasing need for potent acid on demand (patient directed therapy). Drug selection
reduction (ie, PPI long-term maintenance). Physicians depends on clinical presentation, cost-effectiveness, and end
should ask if symptoms have resolved or are persisting. point of appropriate symptom relief.
When needed, an appropriate workup should be instituted
(Figure 1). Do not continue anti-secretory therapy
indefinitely without re-evaluating symptoms. Regular re- Special Circumstances
evaluation can help avoid adverse events and minimize
costs. Older Adults
Since most individuals with GERD do not undergo In patients over the age of 50, new onset GERD is an alarm
endoscopy, chronic acid suppression is tailored to the sign; endoscopy should be the initial diagnostic examination.
individual. Options include: step-up therapy (starting less If reflux is still considered the major cause after negative
potent agents and moving up for treatment response), step- endoscopy, empiric therapy would then be appropriate.
down therapy (using potent acid suppression initially then
decreasing the dose or moving to less potent agents to tailor Pregnancy
to the individual’s response), on demand (patient-directed)
therapy, or surgery. All options have the goal of complete New onset GERD symptoms are common during pregnancy
symptom relief. due mainly to the mechanical pressure placed on the stomach
and intestinal tract as the uterus enlarges. Therapy for GERD
Step-up therapy. If a patient does not respond to an H2RA during pregnancy usually takes a step-wise approach,
within two weeks, the patient should be switched to a PPI, starting with lifestyle modifications often combined with a
again emphasizing it be used 30 minutes to 1 hour prior to trial of calcium containing antacids. If this does not
meals so that the PPI has time to interact with an activated sufficiently treat the symptoms, H2RAs (eg ranitidine) are
pump. considered safe in pregnancy and can be taken to alleviate
symptoms. If symptoms persist despite these efforts, PPIs
If the patient does not respond to this program, double-dose can be considered (caution advised during pregnancy;
PPI therapy (twice daily; 30 minutes before breakfast and 30 possible risk of teratogenicity based on conflicting human
minutes before dinner) may be effective in reducing data).
symptoms. If the patient does not respond to this program,
the patient likely does not have reflux as a source of their
Atypical Manifestations of GERD
symptoms, and diagnostic testing is appropriate.
As noted in Table 1, GERD may manifest atypically as
Approximately 40% of patients requiring PPI therapy will
pulmonary (asthma, chronic cough), laryngeal (laryngitis,
need increasing dosage over time. Tolerance to H2RAs
hoarseness, sore throat, globus, throat clearing), or cardiac
occurs over time. The main goal is to use the lowest dose and
(chest pain) symptoms, often without symptoms of heartburn
least potent medication to obtain a complete and sustained
and regurgitation. Mechanisms include direct contact and
symptomatic response.
microaspiration of small amounts of noxious gastric contents
into the larynx and upper bronchial tree triggering local
Breakthrough symptoms are common and can be treated with
irritation, and cough, and acid stimulation of vagal afferent
antacids and/or nocturnal H2RAs. This approach should be
neurons in the distal esophagus causing non-cardiac chest
limited to those few individuals who are not getting
pain and vagally-mediated bronchospasm or asthma.
symptomatic response, yet have defined reflux as their
Laryngeal neuropathy has been implicated as a cause for
source of symptoms. H2RAs should not be administered at
laryngitis symptoms and cough.
the same time as PPIs and should be taken at bedtime.

8 UMHS GERD Guideline, September, 2013

Pulmonary symptoms. Asthma and GERD are common adults, although a small beneficial effect was seen in
conditions that often coexist, with 50-80% of asthmatics subgroup analysis.
having GERD and up to 75% having abnormal pH testing.
However, only 30% of patients who have both GERD and
asthma will have GERD as the cause for their asthma. The Controversial Areas
causal relationship between asthma and GERD is difficult to
establish because either condition can induce the other. Barrett’s Esophagus Screening and Treatment
GERD can cause asthma as noted above, and asthma can
cause increased reflux by creating negative intrathoracic Barrett’s esophagus is present when intestinal epithelium
pressure and overcoming the lower esophageal sphincter (intestinal metaplasia) replaces normal squamous epithelium
barrier. Furthermore, medications used for asthma, such as in the tubular esophagus. Barrett’s esophagus carries a small
bronchodilators, are associated with increased reflux risk of progressing to esophageal adenocarcinoma. Most
symptoms. Historical clues to GERD-related asthma may patients who develop esophageal adenocarcinoma are
include asthma symptoms that worsen with big meals, believed to progress from Barrett’s epithelium to low-grade
alcohol, or a supine position, or adult-onset and medically dysplasia, then to high-grade dysplasia, and then to cancer.
refractory asthma. Diagnostic testing with pH probe and The overall progression of non-dysplastic Barrett’s
EGD have limited utility in establishing causality in this epithelium to cancer is about 0.2% per year. Symptoms do
population. not predict risk for cancer. Risk factors for progression
include long-segment Barrett’s esophagus, male sex, tobacco
Laryngeal symptoms. In patients presenting with laryngeal use, and likely abdominal obesity. Most patients with low-
symptoms, about 10% of hoarseness, up to 60% of chronic grade dysplasia will revert to non-dysplastic epithelium or
laryngitis and refractory sore throat, and 25-50% of globus remain low grade (60-80%); the progression of high-grade
sensation may be due to reflux. EGD and pH testing are dysplasia to cancer is 6% per year.
frequently normal in this population. Reflux laryngitis is
usually diagnosed based on laryngoscopic findings of Endoscopic surveillance of Barrett’s esophagus is considered
laryngeal erythema and edema, posterior pharyngeal standard, but intervals are very controversial. Since
coblestoning, contact ulcers, granulomas, and interarytenoid progression is variable, the overall incidence of cancer is low
changes. However, a study found these signs to be (6,000-7,000 new cases per year), and surveillance of
nonspecific for GERD, noting at least 1 sign in 91 of 105 Barrett’s esophagus at intervals of less than 5 years is cost-
(87%) healthy people who did not have reflux or laryngeal prohibitive (≥ $100,000 per quality adjusted life-year). The
complaints. Many of these signs may be due to other diagnosis of all types of dysplasia is subject to sampling error
laryngeal irritants such as alcohol, smoking, postnasal drip, and intra- and inter-observer bias. Most overcalling occurs
viral illness, voice overuse, or environmental allergens, between non-dysplastic and low-grade dysplasia and low-
suggesting their use may contribute to over-diagnosis of grade to high-grade dysplasia. Dysplasia should be
GERD. This also may explain why many patients (up to 40- confirmed by two experienced pathologists before surgery or
50%) with laryngeal signs don’t respond to aggressive acid endoscopic treatment is attempted.
therapy. Posterior laryngitis, medial erythema of false or true
vocal cords and contact changes (ulcers and granulomas) are Current accepted monitoring intervals are 3-5 years for no
more common in GERD patients and predict a better dysplasia, 6-12 months for low-grade dysplasia, and 3
response to acid reduction. months for high-grade dysplasia. Endoscopic biopsies
should be done in a standard manner based on past histology.
Treatment. Aggressive acid reduction using PPIs twice Biopsies from nodular areas should be examined separately.
daily before meals for at least 2-3 months is now considered Endoscopy for Barrett’s detection or monitoring should be
the standard treatment for atypical GERD and may be the done only after adequate GERD control for 3 months.
best way to demonstrate a causal relationship between
GERD and extraesophageal symptoms. Double blind, Prevention of cancer in Barrett’s esophagus is also
placebo controlled trials have not shown significant benefit controversial. Proton pump inhibitors should be given to
for PPI twice daily treatment for laryngeal symptoms. control GERD symptoms. Single dose and more intensive
Similar trials in asthma have shown marginal benefits in treatment to eliminate esophageal acid exposure have not
FEV1 rates only when nocturnal GERD symptoms are also been proven to reduce cancer risk. Low-dose aspirin reduces
present. Both groups of studies demonstrate the need for cancer risk, but should be reserved for Barrett’s esophagus
better parameters for patient selection. Anti-reflux surgery patients who have cardiovascular risk factors for which
aimed at controlling asthma through prevention of GERD aspirin is indicated.
has a lower rate of success than anti-reflux surgery aimed at
treating heartburn (45-50% vs. 80-90% respectively). Endoscopic and surgical therapies for Barrett’s esophagus
are evolving. The use of radiofrequency ablation (RFA) or
A systematic review on chronic cough found there is endoscopic mucosal resection (EMR) should be reserved for
insufficient evidence to definitely conclude that PPI high-grade dysplasia confirmed by two pathologists. If
treatment is beneficial for cough associated with GERD in treatment of non-dysplastic or low-grade dysplasia is being
considered, the use of RFA or EMR should be a shared
9 UMHS GERD Guideline, September, 2013
decision-making between the treating physician and the American Gastroenterological Association: Position
patient. Data to date show that reversion to squamous statement on the management of gastroesophageal reflux
epithelium can persist for up to 5 years after endoscopic disease, 2008, literature search through early 2007.
ablation. American Society for Gastrointestinal Endoscopy: Role
of endoscopy in the management of GERD, 2007,
Esophagectomy is the treatment of choice for esophageal literature search through March 2008.
adenocarcinoma. Most patients with high-grade dysplasia
Society of American Gastrointestinal and Endoscopic
can be treated with endoscopic eradication (70-80%). Less
Surgeons: Guidelines for surgical treatment of
morbidity is found with endoscopic ablation than
gastroesophageal reflux disease, 2010, literature search
esophagectomy with gastric pull-up. EMR is valuable to
through early 2006.
determine the existence of cancer with visible mucosal
irregularities in dysplastic epithelium, and may effectively A search of more recent literature was conducted
treat intramucosal cancers. prospectively on Medline from January 2007 (end of AGA
search) through March 2011, except January 2006 was the
Before esophagectomy, patients with high-grade dysplasia or start date for endoscopy (since ASGE search) and January
intramucosal carcinoma should be referred to surgical 2008 was the start date for surgical treatment (since SAGES
centers specializing in the treatment of foregut cancers and search). The major keywords were: gastroesophageal reflux
high-grade dysplasia. disease (or GERD, NERD [non-erosive reflux disease],
NEED [non-erosive esophageal disease]), human adults,
English language, guidelines, clinical trials, and cohort
Treatment for H. pylori studies. Terms used for specific topic searches within the
major key words included: symptoms and classification
Patients with predominant GERD symptoms have a similar (atypical symptoms, heartburn, retrosternal burning
or lower frequency of H. pylori positivity than the general sensation precipitated by meals or a recumbent position,
hoarseness, laryngitis, sore throat, chronic cough, chest
population. Successful treatment of H. pylori has not been
pain, bronchospasm/asthma, dental erosions), eosinophil,
shown to reduce predominant GERD symptoms. Some
studies have shown decreased PPI effectiveness after lymphocytic esophagitis, non acid reflux and weekly acid
successful H. pylori treatment, but this is still controversial. reflux, nocturnal (or nocturnal breakthrough, night time),
One randomized controlled trial demonstrated that H. pylori endoscopy, pH recording, manometry, provocative testing
eradication leads to more resilient GERD. Treatment of H. (Bernstein’s), video esophagography, empiric/therapeutic
trial to acid suppression, lifestyle measures/treatment
pylori is not indicated for patients with GERD.
(avoiding fatty foods, chocolate, peppermints, ethanol-
containing beverages; recumbency for 3 hours after a meal;
elevating head of bed; weight loss), antacids, alginic acid
Related National Guidelines (gaviscon), carafate, prokinetic agents (cisapride,
metoclopramide, bethanechol, dromperidone), H2 receptor
This guideline is consistent with: antagonists (nizatidine, ranitidine, famotidine, cimetidine),
American College of Gastroenterology: Updated guidelines proton pump inhibitors (omeprazole, lansoprazole,
for the diagnosis and treatment of Gastroesophageal rabeprazole, pantoprazole, esomeprazole) – toxicity and
Reflux Disease, 2005 adverse reactions/events, proton pump inhibitors – other
American Gastroenterological Association: Position references, baclofen, fundoplication (open vs. laparoscopy;
statement on the management of gastroesophageal endoscopic antireflux procedures), Barrett's esophagus
reflux disease, 2008 (screening, surveillance). Detailed search terms and strategy
American Society for Gastrointestinal Endoscopy: Role of available upon request.
endoscopy in the management of GERD, 2007
The search was conducted in components each keyed to a
Society of American Gastrointestinal and Endoscopic specific causal link in a formal problem structure (available
Surgeons: Guidelines for surgical treatment of upon request). The search was supplemented with very
gastroesophageal reflux disease, 2010 recent information available to expert members of the panel,
(See annotated references.) including abstracts from recent meetings and results of
clinical trials. Negative trials were specifically sought. The
search was a single cycle.
Strategy for Literature Search
Conclusions were based on prospective randomized
The literature search began with the results of the literature controlled trials if available, to the exclusion of other data; if
searches performed through May 2006 for the previous randomized controlled trials were not available,
versions of this guideline. The results of three more recent observational studies were admitted to consideration. If no
literature searches were initially reviewed and accepted as such data were available for a given link in the problem
adequate through the time they were performed: formulation, expert opinion was used to estimate effect size.

10 UMHS GERD Guideline, September, 2013

 Disclosures American Gastroenterological Association: Kahrilas PJ,
Shaheen NJ, Vaezi MF, Hiltz SW, Black E, Modlin IM,
The University of Michigan Health System endorses the Johnson SP, Allen J, Brill JV. American Gastroenterological
Guidelines of the Association of American Medical Colleges Association Medical Position statement on the management
and the Standards of the Accreditation Council for of gastroesophageal reflux disease. Gastroenterology 2008
Continuing Medical Education that the individuals who Oct; 135(4):1383-91, 1391.e1-5.
present educational activities disclose significant A consensus statement outlining recommendations for the
relationships with commercial companies whose products or diagnosis and treatment of GERD.
services are discussed. Disclosure of a relationship is not
intended to suggest bias in the information presented, but is Standards of Practice Committee, Am Soc for
made to provide readers with information that might be of Gastrointestinal Endoscopy, Lichenstein ER, Cash BD et al.
potential importance to their evaluation of the information. Role of endoscopy in the management of GERD Aug 2007.
Gastrointestinal Endoscopy, 2007; 66(2):219-24.
Team Member Relationship Company
A consensus statement of recommendations concerning
Joel J Heidelbaugh, MD None endoscopy in managing GERD.
Mark A McQuillan, MD Speakers Takeda, Pfizer,
Bureau Astra Zeneca Heidelbaugh JJ, Goldberg KL, Inadomi JM. Adverse risks
R Van Harrison, PhD None associated with proton pump inhibitors: a systematic review.
Timothy T Nostrant, MD None Gastroenterology and Hepatology 2009;5(10):725-34.
A systematic review of the literature which examines
potential risks of PPI therapy.
Review and Endorsement
Heidelbaugh JJ, Nostrant TT. A Cost-Effective Approach to
the Pharmacologic Management of Gastroesophageal Reflux
Drafts of this guideline were reviewed in clinical conferences
Disease. Drug Benefit Trends 2004;16:463-471.
and by distribution for comment within departments and
divisions of the University of Michigan Medical School to An in-depth examination of various cost-effective
which the content is most relevant: Family Medicine, approaches to GERD treatment.
General Medicine, and Gastroenterology. The Executive
Committee for Clinical Affairs of the University of Michigan Heidelbaugh JJ, Nostrant TT. Medical and surgical
Hospitals and Health Centers endorsed the final version. management of gastroesophageal reflux disease. In:
Heidelbaugh JJ (ed). Clinics in Family Practice:
Gastroenterology. Philadelphia, PA: Elsevier, September
2004, 6(3):547-568.
Acknowledgements
A systematic review of the literature and evidence-based
The following individuals are acknowledged for their recommendations for practice in the diagnosis and
contributions to previous versions of this guideline. treatment of GERD.

2002: Clara Kim, MD, General Medicine; R. Van Harrison, Kahrilas, PJ. Gastroesophageal Reflux Disease. JAMA.
PhD, Medical Education; Joel Heidelbaugh, MD, Family 1996;276(12):983-988.
Medicine; Timothy Nostrant, MD, Gastroenterology. A comprehensive review of treatment of GERD with less
emphasis on diagnostic modalities.
2006: Joel J Heidelbaugh, MD, Family Medicine; Arvin S
Gill, MD, Internal Medicine; R. Van Harrison, PhD, Numans Me, Lau J, deWit NJ, Bonis PA. Short-term
Medical Education; Timothy T Nostrant, MD, treatment with proton-pump inhibitors as a test for
Gastroenterology. gastroesophageal reflux disease: a meta-analysis of
diagnostic test characteristics. Annals of Internal Medicine,
2004; 140(7):518-27.
Annotated References A systematic review of this literature, with 15 studies
showing the limited sensitivity and specificity of
American College of Gastroenterology: DeVault KR, Castell successful short-term treatment with PPI in establishing
DO. Updated Guidelines for the Diagnosis and Treatment of the diagnosis when GERD is defined by 24-hour pH
Gastroesophageal Reflux Disease. American Journal of monitoring.
Gastroenterology, 2005; 100:190-200.
Society of American Gastrointestinal and Endoscopic
A consensus statement outlining recommendations in the
Surgeons (SAGES). Guidelines for surgical treatment of
diagnosis and treatment of GERD.
gastroesophageal reflux disease. Los Angeles (CA): Society
11 UMHS GERD Guideline, September, 2013
of American Gastrointestinal and Endoscopic Surgeons
(SAGES); 2010 Feb.
A consensus statement of current recommendations for
surgical treatment of GERD.

Sridhar, S. Clinical economics review: cost-effectiveness of

treatment alternatives for gastro-oesophageal reflux disease.
Alim Pharmacol Ther 1996;10:865-873.
An economic appraisal reviewing different treatment
modalities and their cost-effectiveness. Proton pump
inhibitors are considered more cost effective than H2
receptor antagonists in those with documented erosive
esophagitis.

Vaezi, M. Gastroesophageal reflux disease and the larynx. J

Clin Gastroenterol, 2003; 36(3):198-203.
Presents the rational for an approach to identifying patients
whose laryngeal signs and symptoms are due to GERD.

12 UMHS GERD Guideline, September, 2013