American Gastroenterological Association Institute Technical Review on the Management of Gastroesophageal Reflux Disease
2008; Elsevier BV; Volume: 135; Issue: 4 Linguagem: Inglês
10.1053/j.gastro.2008.08.044
ISSN1528-0012
AutoresPeter J. Kahrilas, Nicholas J. Shaheen, Michael F. Vaezi,
Tópico(s)Eosinophilic Esophagitis
ResumoAt the end of this activity, the successful learner should:1Demonstrate an understanding of the natural history and manifestations of reflux disease2Evaluate the role of diagnostic testing such as endoscopy, esophageal manometry, ambulatory pH monitoring, and impedance-pH monitoring in the management of patients with gastroesophageal reflux disease3Evaluate the options for treatment of patients with complicated and uncomplicated reflux disease. The objectives of this technical review were to evaluate diagnostic and management strategies for patients with gastroesophageal reflux disease (GERD). Specifically, 12 broad questions were developed by interaction among the authors, the American Gastroenterological Association (AGA) Institute, the Clinical Practice and Quality Management Committee, and representatives from the AGA Institute Council. The questions were designed to encapsulate the major management issues leading to consultations for GERD in clinical practice in 2008. The issue of management of Barrett's esophagus was intentionally excluded, because this will be the focus of a later treatise. However, the indications for performing endoscopy were within our purview. For each question, a comprehensive literature search was conducted, pertinent evidence reviewed, and the quality of relevant data evaluated. The resultant conclusions were based on the best available evidence or, in the absence of quality evidence, the expert opinion of the authors of the technical review and medical position statement. The strength of these conclusions was weighed using US Preventive Services Task Force (USPSTF) grades detailed in Table 1. The details of the development methodology used for this and subsequent AGA Institute technical reviews and medical position statements as well as the literature search methodology and yield associated with each of the questions in this technical review are available as a separate document on the AGA Institute Web site.Table 1USPSTF Recommendations and GradesStrength of recommendationsA: The USPSTF strongly recommends that clinicians provide [the service] to eligible patients. The USPSTF found good evidence that [the service] improves important health outcomes and concludes that benefits substantially outweigh harms.B: The USPSTF recommends that clinicians provide [this service] to eligible patients. The USPSTF found at least fair evidence that [the service] improves important health outcomes and concludes that benefits outweigh harms.C: The USPSTF makes no recommendation for or against routine provision of [the service]. The USPSTF found at least fair evidence that [the service] can improve health outcomes but concludes that the balance of benefits and harms is too close to justify a general recommendation.D: The USPSTF recommends against routinely providing [the service] to asymptomatic patients. The USPSTF found at least fair evidence that [the service] is ineffective or that harms outweigh benefits.Insuff: The USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing [the service]. Evidence that the [service] is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined.Quality of evidenceGood: Evidence includes consistent results from well-designed, well-conducted studies in representative populations that directly assess effects on health outcomes.Fair: Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies, generalizability to routine practice, or indirect nature of the evidence on health outcomes.Poor: Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes.NOTE. The USPSTF grades its recommendations according to one of 5 classifications (A, B, C, D, Insuff) reflecting the strength of evidence and magnitude of net benefit (benefits minus harms). The USPSTF grades the quality of the overall evidence for a service on a 3-point scale (good, fair, poor). Open table in a new tab NOTE. The USPSTF grades its recommendations according to one of 5 classifications (A, B, C, D, Insuff) reflecting the strength of evidence and magnitude of net benefit (benefits minus harms). The USPSTF grades the quality of the overall evidence for a service on a 3-point scale (good, fair, poor). GERD has been the most common gastrointestinal diagnosis recorded on outpatient physician visits since 2006, even surpassing abdominal pain.1Shaheen N.J. Hansen R.A. Morgan D.R. et al.The burden of gastrointestinal and liver diseases, 2006.Am J Gastroenterol. 2006; 101: 2128-2138Crossref PubMed Scopus (251) Google Scholar This is remarkable considering the vagaries of the diagnosis. Most patients with heartburn do not have esophagitis, even before treatment,2Sontag S.J. Sonnenberg A. Schnell T.G. et al.The long-term natural history of gastroesophageal reflux disease.J Clin Gastroenterol. 2006; 40: 398-404Crossref PubMed Scopus (36) Google Scholar and this disconnect becomes more exaggerated after empirical antisecretory therapy or with atypical GERD symptoms. Furthermore, although the pathogenesis of reflux esophagitis and reflux symptoms share common elements, the two have several independent determinants as well. Finally, with respect to treatment, potent inhibition of gastric acid secretion reduces the lethality of gastric juice to esophageal epithelial cells such that esophagitis will heal, irrespective of whether or not gastroesophageal reflux is reduced or symptoms are resolved. Ironically, as refractory esophagitis has become a rare clinical problem, refractory “GERD” symptoms has become a substantial one. In the post–proton pump inhibitor (PPI) world, it is patients with symptoms, not esophagitis, who confront the practitioner in the overwhelming majority of clinical encounters for GERD. Regardless of how many citations are identified by literature review, there can be no criterion standard definition of GERD because the threshold distinction between physiologic reflux and reflux disease is ultimately arbitrary. Hence, these questions can only be answered by opinion, and presumably the best opinion upon which to base the answers is that of experts (USPSTF grade and quality not applicable). Fortuitously, a recent and unparalleled attempt at gaining consensus in defining GERD emanated from a panel of world experts utilizing a 4-iteration Delphi process that spanned a 2-year period.3Vakil N. van Zanten S.V. Kahrilas P. et al.The Montreal definition and classification of gastroesophageal reflux disease A global evidence-based consensus.Am J Gastroenterol. 2006; 101: 1900-1920Crossref PubMed Scopus (1335) Google Scholar The stated objective of that unique international consensus group was “to develop a global definition and classification of GERD, using rigorous methodology, that could be used clinically by primary care physicians and that embraces the needs of physicians, patients, researchers, and regulatory bodies from different parts of the world.”3Vakil N. van Zanten S.V. Kahrilas P. et al.The Montreal definition and classification of gastroesophageal reflux disease A global evidence-based consensus.Am J Gastroenterol. 2006; 101: 1900-1920Crossref PubMed Scopus (1335) Google Scholar The output of the Montreal consensus group was a series of 50 statements pertaining to the diagnosis of GERD syndromes. For each statement, the level of consensus was determined by vote along a 6-point scale of agreement ranging from strong agreement to strong disagreement and, when applicable, the quality of supporting evidence was evaluated. An overarching definition of GERD must encompass esophageal as well as extraesophageal syndromes: syndromes with tissue injury as well as those without. Grappling with this dilemma, the Montreal consensus panel reached very strong agreement in defining GERD as “a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications.”3Vakil N. van Zanten S.V. Kahrilas P. et al.The Montreal definition and classification of gastroesophageal reflux disease A global evidence-based consensus.Am J Gastroenterol. 2006; 101: 1900-1920Crossref PubMed Scopus (1335) Google Scholar Thereafter, the panel specified that symptoms were “troublesome” if they adversely affected an individual's well-being and delineated the broad array of GERD syndromes that have been demonstrated or proposed (Figure 1). Note that the extraesophageal syndromes are classified as of established or proposed association, acknowledging that while the evidence on hand is sufficient to link these syndromes to reflux, it is insufficient to establish causation. A test of the word “troublesome” in the Montreal definition of GERD comes in attempting to draw a distinction between GERD and episodic heartburn. The Montreal group believed that for the typical esophageal GERD syndrome, defining a threshold at which heartburn becomes troublesome was useful in planning treatment trials or epidemiologic studies but not in clinical practice. In the individual case, symptom frequency, symptom intensity, and psychosocial factors must also be considered. Hence, in clinical practice, the determination of whether or not heartburn is troublesome should be made by the patient without the use of arbitrary cutoffs for frequency or duration and after the patient is assured of the benign nature of occasional symptomatic heartburn. Presumably, a patient will conclude that if heartburn regularly interferes with his or her normal daily activities, it is troublesome; the more substantial the limitations imposed on his or her life, the more troublesome it is. In clinical trials of symptomatic GERD, a threshold measure of heartburn severity needs to be established for uniformity in the study population. However, there has been little consistency among symptomatic GERD trials in how this was done, with different studies utilizing symptom thresholds as low as 2 mild episodes of heartburn per week and as high as 5 daytime episodes and 1 nighttime episode per week as minimal entry criteria.4Wiklund I. Carlsson J. Vakil N. Gastroesophageal reflux symptoms and well-being in a random sample of the general population of a Swedish community.Am J Gastroenterol. 2006; 101: 18-28Crossref PubMed Scopus (83) Google Scholar, 5Kahrilas P.J. Miner P. Johanson J. et al.Efficacy of rabeprazole in the treatment of symptomatic gastroesophageal reflux disease.Dig Dis Sci. 2005; 50: 2009-2018Crossref PubMed Scopus (28) Google Scholar Dropping the threshold of heartburn severity required to define symptomatic GERD clearly enlarges the “disease” population, and variability in the definition makes comparisons of results among trials difficult, if not impossible. Moving forward with this, the Food and Drug Administration recently issued guidance on the criteria that will be required in the future to support labeling claims.6Guidance for Industry: patient-reported outcome measures: use in medical product development to support labeling claims.http://www.fda.gov/cder/guidance/index.htmDate: 2006Google Scholar The catchphrase has become “patient-reported outcomes.” Patient-reported outcomes measure a patient's health status in terms of symptoms and quality of life as relayed by the patient without the interpretation of the patient's responses by a physician. Disease-specific patient-reported outcomes must be developed and accepted by the Food and Drug Administration before their use in supporting a labeling claim. Acceptance of a patient-reported outcome is predicated on its demonstrated validity, reliability, and ability to identify meaningful differences in disease-specific measures of importance in the intended treatment population. For the example of a patient-reported outcome for symptomatic GERD, both the defining symptom burden and the minimal meaningful increment of improvement attributable to therapy would need to be developed through patient focus groups and vetted by the Food and Drug Administration. Hence, the development of a symptomatic GERD patient-reported outcome will result in defining the threshold symptom burden required for the diagnosis. Needless to say, few, if any, existing trials substantiating treatment efficacy in symptomatic GERD would meet the criteria now mandated by the Food and Drug Administration. In summary, the Montreal definition of GERD was adopted to use as a framework throughout this document. A distinguishing feature of the Montreal definition is that it does not use the term “nonerosive reflux disease,” but rather subdivides esophageal syndromes into symptomatic syndromes and syndromes with esophageal injury. Hence, functional heartburn does not fit the Montreal definition of GERD, whereas it is included under the umbrella of nonerosive reflux disease. The distinction between GERD and episodic heartburn in the Montreal definition is in the word “troublesome.” In the absence of esophageal injury, heartburn of insufficient intensity to be perceived as troublesome by the patient (after assurance of its benign nature) does not meet the Montreal definition of a symptomatic esophageal GERD syndrome. There are a multitude of recommendations regarding lifestyle modifications as GERD therapy. Broadly speaking, these fall into 3 categories: (1) avoidance of foods that may precipitate reflux (coffee, alcohol, chocolate, fatty foods), (2) avoidance of acidic foods that may precipitate heartburn (citrus, carbonated drinks, spicy foods), and (3) adoption of behaviors that may reduce esophageal acid exposure (weight loss, smoking cessation, raising the head of the bed, and avoiding recumbency for 2–3 hours after meals). Most evidence supporting such recommendations is weak, coming from observational and uncontrolled studies of small sample size, often with surrogate end points. In some cases, such as with dietary fat, the evidence is conflicting. Early studies suggested that a high-fat diet was harmful because it diminished lower esophageal sphincter (LES) pressure.7Nebel O.T. Castell D.O. Lower esophageal sphincter pressure changes after food ingestion.Gastroenterology. 1972; 63: 778-783PubMed Google Scholar However, a subsequent controlled study comparing a low-fat diet with a high-fat diet did not find any change in LES pressure or objective reflux parameters by pH monitoring.8Pehl C. Waizenhoefer A. Wendl B. et al.Effect of low and high fat meals on lower esophageal sphincter motility and gastroesophageal reflux in healthy subjects.Am J Gastroenterol. 1999; 94: 1192-1196Crossref PubMed Scopus (54) Google Scholar Similarly, the reported reduction in LES pressure with smoking has not extrapolated to improvement of GERD parameters with cessation of smoking.9Waring J.P. Eastwood T.F. Austin J.M. et al.The immediate effects of cessation of cigarette smoking on gastroesophageal reflux.Am J Gastroenterol. 1989; 84: 1076-1078PubMed Google Scholar The recommendation to elevate the head of the bed by 6–8 inches in patients with reflux is intuitively based on reducing esophageal acid exposure by improving clearance. A corollary to this recommendation is to avoid eating for the 2- to 3-hour period before going to bed, because this is the period during which the most reflux events would be anticipated. There is some merit to this recommendation based on a randomized controlled trial of patients with moderately severe esophagitis (USPSTF grade B, quality fair).10Harvey R.F. Gordon P.C. Hadley N. et al.Effects of sleeping with the bed-head raised and of ranitidine in patients with severe peptic oesophagitis.Lancet. 1987; 2: 1200-1203Abstract PubMed Google Scholar The therapeutic gain from raising the head of the bed with a 20-cm block for the 6-week duration of the study was 20%–30%. However, the subgroup studied (moderate to severe esophagitis) is particularly prone to supine reflux and the applicability of the recommendation of elevation of the head of the bed to the majority of patients with GERD experiencing heartburn predominantly confined to the postprandial period is dubious. Obesity merits special consideration because it has been the object of substantial study in recent years. There is good evidence that GERD is associated with obesity. Specifically, epidemiologic data from the Nurses' Health Study suggest a dose-dependent relationship between increasing body mass index and frequent reflux symptoms,11Jacobson B.C. Somers S.C. Fuchs C.S. et al.Body-mass index and symptoms of gastroesophageal reflux in women.N Engl J Med. 2006; 354: 2340-2348Crossref PubMed Scopus (256) Google Scholar and a large meta-analysis similarly demonstrated a dose-response relationship between body mass index and the risk of reporting symptoms of GERD among both men and women.12Hampel H. Abraham N.S. El-Serag H.B. Meta-analysis Obesity and the risk for gastroesophageal reflux disease and its complications.Ann Intern Med. 2005; 143: 199-211Crossref PubMed Google Scholar Evidence also suggests that acid reflux measured by pH monitoring is increased in obese patients.13El-Serag H.B. Ergun G.A. Pandolfino J. et al.Obesity increases oesophageal acid exposure.Gut. 2007; 56: 749-755Crossref PubMed Scopus (127) Google Scholar Proposed mechanisms for the obesity effect include alteration in the pressure dynamics and anatomy of the esophagogastric junction14Pandolfino J.E. El-Serag H.B. Zhang Q. et al.Obesity A challenge to esophagogastric junction integrity.Gastroenterology. 2006; 130: 639-649Abstract Full Text Full Text PDF PubMed Scopus (234) Google Scholar and an increase in transient LES relaxation and reflux frequency.15Wu J.C. Mui L.M. Cheung C.M. et al.Obesity is associated with increased transient lower esophageal sphincter relaxation.Gastroenterology. 2007; 132: 883-889Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar However, the contention that losing weight will improve GERD is less robustly supported by the literature (USPSTF grade B, quality fair). One observational study of 34 overweight and obese patients found that weight loss resulted in improvement in GERD symptoms,16Fraser-Moodie C.A. Norton B. et al.Weight loss has an independent beneficial effect on symptoms of gastro-oesophageal reflux in patients who are overweight.Scand J Gastroenterol. 1999; 34: 337-340Crossref PubMed Scopus (110) Google Scholar and the Nurses' Health Study analysis found that reflux symptoms were exacerbated or improved over time concomitant with weight gain or loss, respectively.11Jacobson B.C. Somers S.C. Fuchs C.S. et al.Body-mass index and symptoms of gastroesophageal reflux in women.N Engl J Med. 2006; 354: 2340-2348Crossref PubMed Scopus (256) Google Scholar On the other hand, a randomized controlled study did not find any objective or subjective improvement of GERD in 20 obese patients after a significant weight loss.17Kjellin A. Ramel S. Rossner S. et al.Gastroesophageal reflux in obese patients is not reduced by weight reduction.Scand J Gastroenterol. 1996; 31: 1047-1051Crossref PubMed Google Scholar In summary, the problem with advocating lifestyle modifications as GERD therapy is that there are simply too many and each is too narrowly applicable to enforce the whole set on every patient. The Genval Workshop Report on evidence-based reflux management concluded that “there is currently a significant overestimation of the possibility of patients deriving adequate relief from life style modification.”18An evidence-based appraisal of reflux disease management—the Genval Workshop Report.Gut. 1999; 44: S1-S16Crossref PubMed Google Scholar Thus, from the vantage point of high-quality evidence, there are insufficient data to suggest a consistent benefit of lifestyle changes for all patients with GERD (USPSTF grade Insuff). However, it is also clear that there are subsets of patients who may benefit from specific lifestyle modifications and it is good practice to make those recommendations to those patients. A patient with symptoms of nighttime heartburn of sufficient severity to disturb his or her sleep despite acid suppressive therapy may benefit from elevation of the head of the bed. Similarly, a patient who consistently experiences troublesome heartburn after ingestion of alcohol, coffee, or spicy foods despite acid suppressive therapy will benefit from avoidance of these factors. Finally, if the development of troublesome heartburn paralleled weight gain, it is perfectly reasonable to propose weight loss as an intervention that may prevent, or at least postpone, the need for continuous acid suppressive therapy. Initiating empirical treatment with a PPI amounts to a pragmatic therapeutic trial; if a patient reports symptoms consistent with GERD and responds to therapy for GERD, then he or she must have GERD. However, the notion that this constitutes a clinical test blurs the distinction between healing esophagitis and resolving putative reflux symptoms, the latter of which are neither perfectly sensitive nor specific for GERD. Such reasoning also ignores the existence of other diagnostic possibilities that may benefit from PPI therapy or a possible placebo response. The strategy of empirical therapy is also limited by the observation that PPI therapy is not as robust at resolving GERD symptoms as it is resolving esophagitis; a negative response to a PPI trial does not exclude GERD as a diagnostic possibility. Furthermore, it dampens the diagnostic utility of endoscopy because esophagitis, which would otherwise have been a robust marker of GERD, will likely be healed with treatment regardless of whether or not symptoms resolve. Nonetheless, these limitations withstanding, the current consensus is that empirical PPI therapy is appropriate for uncomplicated heartburn.3Vakil N. van Zanten S.V. Kahrilas P. et al.The Montreal definition and classification of gastroesophageal reflux disease A global evidence-based consensus.Am J Gastroenterol. 2006; 101: 1900-1920Crossref PubMed Scopus (1335) Google Scholar, 19DeVault K.R. Castell D.O. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease.Am J Gastroenterol. 2005; 100: 190-200Crossref PubMed Scopus (530) Google Scholar, 20Armstrong D. Marshall J.K. Chiba N. et al.Canadian Consensus Conference on the management of gastroesophageal reflux disease in adults—update 2004.Can J Gastroenterol. 2005; 19: 15-35Crossref PubMed Google Scholar As for the choice of therapeutic agent, there is an abundance of data demonstrating the effectiveness of PPIs in healing esophagitis and in relieving heartburn. A recent Cochrane review examined 134 treatment trials including 36,978 patients with esophagitis and concluded that PPIs exhibit a better healing effect and faster symptom relief than histamine2 receptor antagonists (H2RAs), which are in turn better than placebo.21Khan M. Santana J. Donnellan C. et al.Medical treatments in the short term management of reflux oesophagitis.Cochrane Database Syst Rev. 2007; 2 (CD003244)Google Scholar That review also concluded that there is no major difference in efficacy among the currently available PPIs (esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole) and that the gain achieved by doubling the standard dose of PPI therapy is modest. Available 6- to 12-month data also suggest that PPIs are effective for maintaining symptom relief and preventing recurrence of esophagitis in patients who respond to an acute course of the same therapy. Table 2 summarizes the major observations from this voluminous pool of therapeutic data.22Dean B.B. Gano Jr, A.D. Knight K. et al.Effectiveness of proton pump inhibitors in nonerosive reflux disease.Clin Gastroenterol Hepatol. 2004; 2: 656-664Abstract Full Text Full Text PDF PubMed Scopus (265) Google Scholar, 23Chiba N. De Gara C.J. Wilkinson J.M. et al.Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease A meta-analysis.Gastroenterology. 1997; 112: 1798-1810Abstract Full Text Full Text PDF PubMed Scopus (618) Google Scholar, 24Sabesin S.M. Berlin R.G. Humphries T.J. et al.Famotidine relieves symptoms of gastroesophageal reflux disease and heals erosions and ulcerations Results of a multicenter, placebo-controlled, dose-ranging study.Arch Intern Med. 1991; 151 (USA Merck Gastroesophageal Reflux Disease Study Group): 2394-2400Crossref PubMed Google Scholar, 25Venables T.L. Newland R.D. Patel A.C. et al.Omeprazole 10 milligrams once daily, omeprazole 20 milligrams once daily, or ranitidine 150 milligrams twice daily, evaluated as initial therapy for the relief of symptoms of gastro-oesophageal reflux disease in general practice.Scand J Gastroenterol. 1997; 32: 965-973Crossref PubMed Google Scholar, 26van Pinxteren B. Numans M.E. Bonis P.A. et al.Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease.Cochrane Database Syst Rev. 2006; 3 (CD002095)PubMed Google Scholar, 27Kahrilas P.J. Fennerty M.B. Joelsson B. High- versus standard-dose ranitidine for control of heartburn in poorly responsive acid reflux disease: a prospective, controlled trial.Am J Gastroenterol. 1999; 94: 92-97Crossref PubMed Scopus (46) Google Scholar, 28Johnson D.A. Benjamin S.B. Vakil N.B. et al.Esomeprazole once daily for 6 months is effective therapy for maintaining healed erosive esophagitis and for controlling gastroesophageal reflux disease symptoms: a randomized, double-blind, placebo-controlled study of efficacy and safety.Am J Gastroenterol. 2001; 96: 27-34Crossref PubMed Google Scholar, 29Vaezi M.F. Richter J.E. Stasney C.R. et al.Treatment of chronic posterior laryngitis with esomeprazole.Laryngoscope. 2006; 116: 254-260Crossref PubMed Scopus (177) Google Scholar, 30Kiljander T.O. Harding S.M. Field S.K. et al.Effects of esomeprazole 40 mg twice daily on asthma: a randomized placebo-controlled trial.Am J Respir Crit Care Med. 2006; 173: 1091-1097Crossref PubMed Scopus (137) Google Scholar, 31Chang A.B. Lasserson T.J. Kiljander T.O. et al.Systematic review and meta-analysis of randomised controlled trials of gastro-oesophageal reflux interventions for chronic cough associated with gastro-oesophageal reflux.BMJ. 2006; 332: 11-17Crossref PubMed Google Scholar Thus, abundant data support treating patients with esophageal GERD syndromes with antisecretory drugs (USPSTF grade A, quality good) and there is ample evidence that, as a drug class, PPIs are more effective in these patients than are H2RAs (USPSTF grade A, quality good). However, the data supporting the use of PPIs with doses higher than the standard are minimal. Similarly, there is no evidence of improved long-term efficacy by adding a nocturnal dose of an H2RA to twice-daily PPI therapy (USPSTF grade Insuff). This combination was proposed to suppress “nocturnal acid breakthrough” on the assumption that this was clinically relevant.32Peghini P.L. Katz P.O. Castell D.O. Ranitidine controls nocturnal gastric acid breakthrough on omeprazole: a controlled study in normal subjects.Gastroenterology. 1998; 115: 1335-1339Abstract Full Text Full Text PDF PubMed Google Scholar However, subsequent data have failed to show any associated clinical benefit.33Fackler W.K. Ours T.M. Vaezi M.F. et al.Long-term effect of H2RA therapy on nocturnal gastric acid breakthrough.Gastroenterology. 2002; 122: 625-632Abstract Full Text Full Text PDF PubMed Google Scholar, 34Ours T.M. Fackler W.K. Richter J.E. et al.Nocturnal acid breakthrough: clinical significance and correlation with esophageal acid exposure.Am J Gastroenterol. 2003; 98: 545-550Crossref PubMed Scopus (75) Google Scholar, 35Vakil N. Guda N. Partington S. The effect of over-the-counter ranitidine 75 mg on night-time heartburn in patients with erosive oesophagitis on daily proton pump inhibitor maintenance therapy.Aliment Pharmacol Ther. 2006; 23: 649-653Crossref PubMed Scopus (12) Google Scholar There are also no high-quality data supporting the use of metoclopramide as either monotherapy or adjunctive therapy in esophageal or suspected extraesophageal GERD syndromes, making the toxicity profile of the drug36Miller L.G. Jankovic J. Metoclopramide-induced movement disorders Clinical findings with a review of the literature.Arch Intern Med. 1989; 149: 2486-2492Crossref PubMed Google Scholar ample grounds for recommending against its use (USPSTF grade D, quality fair). Finally, data supporting the use of PPIs for treatment of patients with extraesophageal GERD syndromes with an established association are weak (USPSTF grade B, quality fair).Table 2Summary of GERD Treatment Data With Inhibitors of Gastric Acid SecretionEsophagitis healing (all severities)PPIs are superior to placebo: 83% vs 18% at 8 wk, NNT = 1.721Khan M. Santana J. Donnellan C. et al.Medical treatments in the short term management of reflux oesophagitis.Cochrane Database Syst Rev. 2007; 2 (CD003244)Google ScholarPPIs dose-response curve exhibits a plateau: low vs standard dose, NNT = 10 at 4 wk; standard vs high or split dose, NNT = 25 at 4 wk21Khan M. Santana J. Donnellan C. et al.Medical treatments in the short term management of reflux oesophagitis.Cochrane Database Syst Rev. 2007; 2 (CD003244)Google ScholarPPIs are superior to H2RAs: 84% vs 52%,20Armstrong D. Marshall J.K. Chiba N. et al.Canadian Consensus Conference on the management of gastroesophageal reflux disease in adults—update 2004.Can J Gastroenterol. 2005; 19: 15-35Crossref PubMed Google Scholar RR = 0.5121Khan M. Santana J. Donnellan C. et al.Medical treatments in the short term management of reflux oesoph
Referência(s)