Guidelines for the Diagnosis and Treatment of Gastroesophageal Reflux Disease Kenneth R. DeVault, MD; Donald O. Castell, MD; for the Practice Parameters Committee of the American College of Gastroenterology

Gastroesophageal

reflux disease (GERD) is a common disorder that affects all segof the population. These guidelines have been prepared to suggest the preferable, but not only, approaches to the management of a patient with GERD. The physician must be free to choose the course best suited to the individual patient. The world literature was reviewed and the guidelines were developed under the auspices of the American College of Gastroenterology, and approved by other gastroenterology societies. Diagnostic recommendations include the following: (1) general approach to GERD, including empiric therapy, (2) appropriate mucosal evaluation (ie, endoscopy and radiology), (3) use of pH and provocative testing, and (4) indications for manometric evaluation. Therapeutic recommendations include the following: (1) general approach to therapy including lifestyle changes, (2) use of acid suppression, (3) use of promotility drugs, (4) maintenance treatment of GERD, and (5) indications for antireflux surgery. (Arch Intern Med. 1995;155:2165-2173) ments

These

guidelines indicate preferable ap¬ proaches to the management of patients with gastroesophageal reflux disease (GERD) (Table I). The

term

gastro¬

esophageal reflux disease will be used to refer to the symptoms and tissue damage that result from abnormal reflux of gas¬

tric contents into the esophagus. When the

only data available will not withstand ob¬

jective scrutiny, the recommendation is a

of experts. The guidelines ap¬ ply to all physicians who address GERD and are intended to indicate the prefer¬ able, but not the only, acceptable ap¬ proach to this problem. Given the wide range of specifics in any health care prob¬ lem, physicians must always choose the consensus

best suited to individual patients and the variables that exist at the mo¬ ment of decision. These guidelines are in¬ tended for adult patients; other groups are developing guidelines for the treatment of course

pediatrie patients.

Mayo Clinic, Jacksonville, Fla (Dr DeVault); The Graduate Hospital, Philadelphia, Pa (Dr Castell); and the Practice Parameters Committee of the American College of Gastroenterology, Arlington, Va. A complete listing of the members of the Practice Parameters Committee can be found in the "Acknowledgment" section. From the

These guidelines were developed un¬ der the auspices of the American College of Gastroenterology and its Practice Pa¬ rameters Committee and approved by the Board of Trustees. The guidelines have been reviewed and revised by the committee, other experts in the field, physicians who will use them, and specialists in the sci¬ ence of decision analysis. The American College of Gastroenterology recommenda¬ tions are considered valid at the time of their publication based on the data available. METHODS

The world literature was reviewed using the National Library of Medicine as a da¬ tabase. All appropriate studies were re¬ viewed and evaluated by us. References in these reports that seemed to contribute to this topic also were evaluated. In the re¬ view, evidence was evaluated along a hi¬ erarchy, with randomized, controlled tri¬ als given the greatest weight. Abstracts presented at national and international meetings were used only when unique data from ongoing trials were presented. When scientific data were lacking, recommen¬ dations were based on expert consensus.

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Table 1. Recommendations for Diagnosis and Treatment of Gastroesophageal Reflux Disease of the Practice Parameters Committee of the American College of Gastroenterology

the benign course of these mally symptomatic patients.

WHEN IS GERD NOT A BENIGN PROCESS?

Recommendation

Diagnosis

If the

General

Mucosal evaluation

patient's history is typical for uncomplicated gastroesophageal reflux disease (GERD), an initial trial of empiric therapy (including lifestyle modification) is appropriate. Patients in whom empiric therapy is unsuccessful or who have symptoms suggesting complicated disease should have further diagnostic testing. Endoscopy with biopsy is the primary technique for evaluating mucosal integrity. If unavailable, double-contrast radiography may be used.

pH

and

provocative testing

Esophageal manometry Treatment General

Acid suppression

Promotility agents Maintenance therapy

Surgery

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 on therapy. Provocative tests have a limited usefulness in the routine diagnosis and therapy of GERD. Manometry is indicated and In certain complicated cases may be helpful before an antireflux procedure Is performed. Lifestyle modification should be Initiated and continued throughout the course of GERD therapy. Acid suppression is the mainstay of therapy for GERD. Histamine2-receptor blackers given in divided doses are effective treatment In many patients. Proton pump inhibitors provide rapid symptomatic relief and healing of esophagitls in the highest percentage of patients. Promotility agents such as cisapride and domperidone have an efficacy similar to standard-dose histamine2 receptors, with fewer serious side effects than the older agents (bethanechol chloride and metoclopramide hydrochloride). Because GERD ¡s 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. Surgery should be considered if medical therapy falls or is deemed appropriate in Individual cases.

Gastroesophageal reflux disease rep¬

wide spectrum of disease. When patients become concerned about and limited by their symp¬ toms, they seek care from a physi¬ cian. Control of these symptoms is important, and proper therapy de¬ mands accurate diagnosis. In addi¬ tion to the usual symptoms of heart¬ burn and régurgitation, patients may suffer morbidity from mucosal dam¬ age to the esophagus or from the extraesophageal manifestations of GERD or both. The histologie mani¬ festations of GERD are usually con¬ fined to the mucosal layer and con¬ sist of inflammatory cell infiltration of the squamous epithelium, thick¬ ening of the basal cell layer, and sloughing of the surface epithelial cells.4 Deep esophageal ulcération and perforation are uncommon (no data for their prevalence exist). This inflammatory process may progress resents a

to peptic esophageal stricturing. Specific antireflux therapy has not been shown to change the out¬ come

of these GERD-related

During preparation, the guidelines

submitted for review by the Practice Committees and Govern¬ ing Boards of the American Gastroenterological Association and the American Society for Gastrointesti¬ nal Endoscopy. All recommenda¬ tions resulting from this review were carefully considered by the commit¬ tee and incorporated in the final re¬ vision. In addition, the guidelines were circulated for review and com¬ ment to primary internal medicine and family practice societies and to the members of the American Col¬ lege of Gastroenterology. BACKGROUND

Gastroesophageal reflux disease is a common clinical problem that af¬ fects all segments of the popula¬ tion. An epidemiologie study sug-

gested that about 10% of the US population may have daily heart¬

burn, and that more than one third have intermittent symptoms.1 Most long-term antacid use is for selfmedication of symptoms of GERD.2 A study that followed up patients di¬ agnosed with mild esophagitis showed that 23% of patients pro¬ gressed to a more severe form, 31% improved, and 46% spontaneously healed and had no further episodes of esophagitis.3 This suggests an of¬ ten benign process in the patients with minimal symptoms who rarely visit a physician. We will limit our recommendations to the recur¬ rently symptomatic group, know¬ ing that at least some people who are asymptomatic and minimally symp¬ tomatic may progress to complica¬ tions of GERD. Further prospec¬ tive studies are needed to confirm

com¬

plications, although one report suggested a decrease in necessity for repeat esophageal dilations in

patients treated with

were

mini¬

pump inhibitor.3

a

proton

Metaplastic columnar (Bar¬ rett's) epithelium and its potential

for malignant transformation is recognized as a complication of GERD.67 Barrett's epithelium may develop in 10% to 15% of the pa¬ tients with chronic GERD.8"11 The risk of malignancy in patients with Barrett's epithelium may be up to 30 to 40 times that of the general popu¬ lation, although this is an area of

controversy.12"15 Peptic esophageal

stricture often may coexist with Bar¬ rett's epithelium. The prevalence has not been determined, but in one se¬ ries, Barrett's epithelium was found in 44% of patients with a stricture related to reflux.16 In addition, up to 25% of patients with Barrett's epi¬

thelium have a proximal esopha¬ geal stricture.17 We will discuss Bar¬ rett's epithelium in reference to the diagnosis and treatment of GERD;

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other guidelines will be developed to address specific problems in the management of known Barrett's

esophagus.

contrast barium studies,

GENERAL CONCEPTS IN THE DIAGNOSIS OF GERD

Establishing that a patient's symp¬ toms are caused by gastroesopha¬ geal reflux can be approached in various ways, but often a carefully taken history discloses symptoms consistent with complicated or un¬ complicated GERD. Heartburn (py¬ both after

rosis) régurgitation a meal, especially a large or fatty meal, aggravated by recumbency or or

or

bending and relieved by antacids are the typical symptoms of GERD. Usu¬ ally, no further testing is needed be¬ fore beginning empiric therapy in this classic presentation. The large

number of persons with symptoms of heartburn and régurgitation pre¬ cludes initial comprehensive evalu¬ ation of all patients, although the cost of therapy without a firm diag¬ nosis must also be considered. Em¬ piric therapy with the possible ad¬ vantages of cost and convenience to patients and physicians must be weighed against the possible risk of misdiagnosis and inadequate therapy of more severe conditions. No costbenefit analysis of this patient group has been reported. Several less typical symptoms may be related to GERD and are usu¬ ally referred to as "atypical symp¬ toms." An association with GERD may occur in up to 50% of patients with noncardiac chest pain,18 78% of patients with chronic hoarseness,19 and 82% of patients with asthma.20 Chronic cough has also been asso¬ ciated with GERD.2122 Gastroesopha¬ geal reflux may be induced by ex¬ ercise and can be asymptomatic or present with typical or atypical symptoms.23,24 Dental erosions also have been associated with asymp¬ tomatic

gastrointestinal endoscopy.26 Esophagitis and even small neo¬ plasms may be shown on doublegram and upper

gastroesophageal reflux.25

Evaluation for Mucosal

Injury

If empiric therapy is unsuccessful, or if patients have complicated or re¬ current disease, determination of the presence of mucosal injury is im¬

portant. Diagnostic options in¬ clude air-contrast barium

esopha-

yet, in up to

third of the patients, the esophagogastric junction is not well dis¬ tended, and abnormalities may be missed.27 When the data from com¬ parisons of barium radiography with endoscopy with biopsy specimen are combined, the diagnostic accuracy of radiography is 24.6% when esophagitis is mild, 81.6% when it is moderate, and 98.7% when it is severe.2831 Even more difficult for ra¬ diologie studies is determination of one

esophagus vs routine esophagitis. Although a reticular mu¬ cosal pattern on barium study has been suggested as a specific radiologic finding in columnar-lined esophagus, histologie evaluation is the standard, and biopsy is re¬ quired for the specific diagnosis of dysplasia.32·33 Reflux of barium is of unproven significance, and even Barrett's

with provocative tests is positive in 25% to 71% of symptomatic pa¬ tients but can be seen in up to 20% of normal controls.34,35 The lack of sensitivity and specificity of these tests limits their ability to predict mucosal injury. Similarly, a sliding hiatal hernia has limited diagnostic accuracy, although it may predis¬ pose to GERD.31·36 Endoscopy has the advantage of providing direct visualization and bi¬ opsy of the esophageal mucosa. Up to 40% of patients may have histo¬ logie changes alone and can be di¬ agnosed only with endoscopie bi¬ opsy. Total endoscopie costs may be as much as three times those of barium radiography, but no costbenefit analysis has been per¬ formed. Provocative Tests

The presence of mucosal injury does not, however, provide absolute proof that the patient's symptoms are caused by reflux, nor do normal bi¬ opsy findings rule out GERD. Many patients with typical GERD symp¬ toms and abnormal esophageal acid exposure do not have esophagi¬

tis.37 Thus, a diagnostic maneuver to establish a causal relation between

intraesophageal

acid and the pa-

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tient's symptoms is

an

important

component of the evaluation. The Bernstein test of mucosal

sensitivity to acid in the documen¬ tation of acid-related symptoms pro¬ approximately 80% sensitiv¬

vides

ity.38 This test involves the infusion of 0.1 hydrochloric acid into the esophagus with a saline control as placebo. A positive test is defined as reproduction of the patient's symp¬ toms with acid perfusion, but not with placebo. This test is more likely to

be positive in patients with more

esophagitis.39 One potential problem with the Bernstein test is the severe

diminished positivity in patients with Barrett's esophagus.40 An¬ other problem is variability in tech¬ nique, eg, increasing the duration of the infusion increases the sensitiv¬ ity but decreases the specificity. In 1985, Richter41 combined seven re¬ ported series (298 patients and 140 controls) and found an overall sen¬ sitivity of 77% and specificity of 86%. The Bernstein test may establish that symptoms are related to GERD, but it does not differentiate between de¬ grees of reflux or esophagitis. Other provocative tests in¬ clude maneuvers to induce reflux during the barium esophagram or with the standard acid reflux test. These tests are reproducible, but at least 20% of controls will have an ab¬ normal test.42·43 Scintigraphic deter¬ mination of reflux has also been re¬ ported. The usual method is to give an intragastric bolus of radiolabeled technetium, followed by ma¬ neuvers similar to those already de¬ scribed. The sensitivity of this technique ranges from 14% to 90%.4446 A recent report found scintigraphy to be insensitive (36%) when compared with 24-hour pH testing, and to be positive in only 50% of patients with esophagitis.47

pH Testing

Prolonged ambulatory intraesophageal pH monitoring identifies exces¬ sive reflux with or without a posi¬ tive symptom association.48 The

of ambulatory pH testing is between 84% and 93%.49 Up to a 96% sensitivity and speci¬ ficity was noted using prolonged pH monitoring to differentiate be¬ tween 45 controls and 45 patients

reproducibility

with typical reflux symptoms.50 The finding of normal acid exposure in 23% to 29% of the patients with documented esophagitis,51·52 and the questions raised by differences in the amounts of gastroesophageal re¬ flux recorded with the simulta¬ neous monitoring of esophageal pH with two connected probes,53 has shed some doubt on this test as a "gold standard." Sensitivity and specificity are difficult to evaluate without an additional standard to compare with ambulatory monitor¬ ing. Although this test is typically performed for 24 hours, shorter pe¬ riods of monitoring have recently been evaluated and may provide adequate information in some

subjects.54·55

Patients with symptoms typi¬ cal for GERD and with docu¬

mented esophagitis do not benefit from an initial pH study. Patients with atypical symptoms of reflux, es¬ pecially those with unexplained chest pain and without esophagi¬ tis, may have clarification of their syndrome with pH testing.56·57 Pa¬ tients with pulmonary symptoms or chronic hoarseness may also ben¬ efit from ambulatory pH monitor¬ ing.19"22 The pattern of reflux as de¬ fined by ambulatory pH testing provides prognostic information be¬ cause supine (or combined supine and upright) reflux is associated with resistant esophagitis compared with reflux occur¬ ring only during the upright pe¬ more severe

when

riod.58 An additional use of pH moni¬ toring is in the evaluation of patients whose symptoms continue while they are receiving therapy. Some of these patients have continued ab¬ normal acid exposure despite ag¬ gressive acid suppression.59 Fi¬ nally, the evaluation of "bile" or "alkaline" reflux with ambulatory pH testing is under study, although the clinical importance of this concept is debated.60

Esophageal

Antacids and Antirefluxants

with a manometry catheter is often necessary and provides an opportu¬ nity for full manometry. The find¬ ing of a high percentage of abnor¬ mal contractions or the presence of a hypotensive LES or both not only suggests a more severe form of GERD, but also implies greater dif¬ ficulty with long-term therapy.63·64 In a review of six studies, the find¬ ing of an LES pressure less than 10 mm Hg had a low sensitivity (58%) and specificity (84%) for abnormal acid exposure.63 The role of peristal¬ tic dysfunction in GERD is un¬ clear, but a recent study showed that 50% of patients with mild to severe esophagitis had some impairment of

The use of antacids and alginic acid

is a part of GERD therapy.78 They raise the pH of the refluxed gastric content, and therefore have the ad¬ vantage of deactivating pepsin. It is

important to teach the patient that

these over-the-counter medica¬ tions are an appropriate compo¬ nent of GERD therapy and to ex¬ plain their mechanism of action and proper use. Antacids79 and alginic acid80·81 are more effective than pla¬ cebo in relieving symptoms in¬ duced by a heartburn-promoting meal. In addition, combined ant¬ acid and alginic acid therapy may be superior to antacids alone in the con¬ trol of symptoms.82·83 Although no studies have evaluated the effective¬ ness of combined antacid and life¬ style modification as therapy for GERD, two long-term trials sug¬ gest effective relief of symptoms in about 20% of patients.64·84

esophageal peristalsis.66 Transient

LES relaxations may be a major mechanism of GERD, but are noted

infrequently during diagnostic ma¬ nometry.67 Esophageal manometry

document the presence of effec¬ esophageal peristalsis may be helpful in patients in whom antire¬ flux surgery is being considered.68 to

tive

Acid

GENERAL PRINCIPLES IN THE THERAPY OF GERD

Education of the patient about the nature of GERD and the factors that may precipitate reflux should be the cornerstone of therapy. All pa¬ tients with GERD should be coun¬ seled on lifestyle modifications that may improve GERD symptoms.69,70 Numerous physiologic studies show that elevation of the head of the bed,71-72 decreased fat intake,73 ces¬ sation of smoking,74 and avoiding re¬ cumbency for 3 hours postprandially decrease distal esophageal acid exposure. In addition, chocolate,75 peppermint,76 and perhaps onions and garlic77 increase esophageal re¬ flux and should be avoided.

The four

fectiveness of these agents have Studies of symptomatic response and healing of esophagitis are summarized in Table 2 and listed in Table 3.85"117 Duration of treatment and the defi¬ nition of symptom responses and healing vary, but, in general, when standard dosages of H2RAs (equiva-

yielded variable results.

Suppression No.

(LES).61·62 Therefore, an intubation

Placebo

Histamine2-receptor antagonists* Omeprazolef

an¬

United States (cimetidine hydro¬ chloride, ranitidine hydrochloride, famotine hydrochloride, and nizatidine) given in divided doses are the mainstay in the treatment of acid peptic disorders, including GERD. Despite this widespread accep¬ tance, controlled studies of the ef¬

Manometric Studies

Esophageal motility studies may pro¬ vide diagnostic and prognostic in¬ formation. The accurate placement of esophageal pH probes is facili¬ tated by manometric localization of the lower esophageal sphincter

histamine2-receptor

tagonists (H2RAs) marketed in the

Table 2. Summary of Studies Evaluating Acid for Gastroesophageal Reflux Disease

Treatment

Suppression

(%) of Patients

Symptomatic Response 152/562 (27) 1132/1887(60) 695/834 (83)

Healing 104/433(24) 506/1003(50) 591/754 (78)

*Dose ranges were cimetidine hydrochloride, 800 to 1600 mg/d; rannidine hydrochloride, 300 to 600 mg/d; nizatidine, 600 mg/d; famotine hydrochloride, 40 mg/d; all given in divided doses either twice daily or four times daily. tOnce daily in a range of 20 to 60 mg/d.

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Table 3. Randomized Trials of Acid

Treatment of Patients)*

Source, y Behar et al,85 1978

Cimetidine, 300 mg QID (28) Placebo

Placebo

Brown,881979 and

Bright-Asare

El-Bassouissi,891980

Rasse et al,901980

Goy et al,9'

1983

Wesdorp

al,921983

et

Fielding

and

Hine et

al,941984

Doyle,931984

Snerbaniuk et

al,951984

Johansson et

al,961986

Kaul et al,971986

al,981986

Koelz et

Lehtola et al,991986

Klinkenberg-Knol Sontag

et

et

al,1001987

al,101 1987

Havelund et al,1021988

al,'031988

Hetzel et

Sandmark et al,1041988

al,1051988

Vantrappen

et

Johnson et

al,1061989

Zeitoun et al,1071989 Bate et

Farup

al,1081990

et

al,1091990

Lundell et al,1101990 Maleev et al,111 1990

Maxton et al,'121990 Quik et al,"31990

Sontag

et

al,'141992

Sabesin et al.,1s 1991 Euler et

al,1161993

Cloud et al,1171992

*QID indicates four times

jP