Medical management of gastroesophageal reflux disease in adults
- Peter J Kahrilas, MD
Peter J Kahrilas, MD
- Professor of Medicine
- Feinberg School of Medicine, Northwestern University
The passage of gastric contents into the esophagus (gastroesophageal reflux) is a normal physiologic process. Most episodes are brief and do not cause symptoms, esophageal injury, or other complications. Gastroesophageal reflux becomes a disease when it either causes macroscopic damage to the esophagus or causes symptoms that reduce the quality of life.
This topic will review the initial management of gastroesophageal reflux disease (GERD) and maintenance therapy for patients with recurrent GERD when treatment is discontinued. Our recommendations are largely consistent with the American Gastroenterological Association and the American College of Gastroenterology guidelines [1,2]. The evaluation and management of refractory GERD and the role of surgery and endoscopic therapy in patients with GERD are discussed separately. (See "Approach to refractory gastroesophageal reflux disease in adults" and "Surgical management of gastroesophageal reflux in adults" and "Radiofrequency treatment for gastroesophageal reflux disease".)
Gastroesophageal reflux disease (GERD) is defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications .
GERD is classified based on the appearance of the esophageal mucosa on upper endoscopy into the following:
●Erosive esophagitis is characterized by endoscopically visible breaks in the distal esophageal mucosa with or without troublesome symptoms of GERD. (See "Clinical manifestations and diagnosis of gastroesophageal reflux in adults", section on 'Esophagitis on esophagoscopy'.)
- Kahrilas PJ, Shaheen NJ, Vaezi MF, et al. American Gastroenterological Association Institute technical review on the management of gastroesophageal reflux disease. Gastroenterology 2008; 135:1392.
- Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol 2013; 108:308.
- Vakil N, van Zanten SV, Kahrilas P, et al. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol 2006; 101:1900.
- Shaheen NJ, Weinberg DS, Denberg TD, et al. Upper endoscopy for gastroesophageal reflux disease: best practice advice from the clinical guidelines committee of the American College of Physicians. Ann Intern Med 2012; 157:808.
- ASGE Standards of Practice Committee, Evans JA, Early DS, et al. The role of endoscopy in Barrett's esophagus and other premalignant conditions of the esophagus. Gastrointest Endosc 2012; 76:1087.
- American Gastroenterological Association, Spechler SJ, Sharma P, et al. American Gastroenterological Association medical position statement on the management of Barrett's esophagus. Gastroenterology 2011; 140:1084.
- Inadomi JM, Jamal R, Murata GH, et al. Step-down management of gastroesophageal reflux disease. Gastroenterology 2001; 121:1095.
- Inadomi JM, McIntyre L, Bernard L, Fendrick AM. Step-down from multiple- to single-dose proton pump inhibitors (PPIs): a prospective study of patients with heartburn or acid regurgitation completely relieved with PPIs. Am J Gastroenterol 2003; 98:1940.
- Tsuzuki T, Okada H, Kawahara Y, et al. Proton pump inhibitor step-down therapy for GERD: a multi-center study in Japan. World J Gastroenterol 2011; 17:1480.
- Kahrilas PJ, Fennerty MB, 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.
- Sontag SJ. The medical management of reflux esophagitis. Role of antacids and acid inhibition. Gastroenterol Clin North Am 1990; 19:683.
- Kaltenbach T, Crockett S, Gerson LB. Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence-based approach. Arch Intern Med 2006; 166:965.
- Aslam M, Slaughter JC, Goutte M, et al. Nonlinear relationship between body mass index and esophageal acid exposure in the extraesophageal manifestations of reflux. Clin Gastroenterol Hepatol 2012; 10:874.
- Cremonini F, Locke GR 3rd, Schleck CD, et al. Relationship between upper gastrointestinal symptoms and changes in body weight in a population-based cohort. Neurogastroenterol Motil 2006; 18:987.
- Kjellin A, Ramel S, Rössner S, Thor K. Gastroesophageal reflux in obese patients is not reduced by weight reduction. Scand J Gastroenterol 1996; 31:1047.
- Jacobson BC, Somers SC, Fuchs CS, et al. Body-mass index and symptoms of gastroesophageal reflux in women. N Engl J Med 2006; 354:2340.
- Ness-Jensen E, Lindam A, Lagergren J, Hveem K. Weight loss and reduction in gastroesophageal reflux. A prospective population-based cohort study: the HUNT study. Am J Gastroenterol 2013; 108:376.
- DeVault KR, Castell DO, American College of Gastroenterology. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol 2005; 100:190.
- Ness-Jensen E, Hveem K, El-Serag H, Lagergren J. Lifestyle Intervention in Gastroesophageal Reflux Disease. Clin Gastroenterol Hepatol 2016; 14:175.
- Eherer AJ, Netolitzky F, Högenauer C, et al. Positive effect of abdominal breathing exercise on gastroesophageal reflux disease: a randomized, controlled study. Am J Gastroenterol 2012; 107:372.
- Ness-Jensen E, Lindam A, Lagergren J, Hveem K. Tobacco smoking cessation and improved gastroesophageal reflux: a prospective population-based cohort study: the HUNT study. Am J Gastroenterol 2014; 109:171.
- Simon B, Ravelli GP, Goffin H. Sucralfate gel versus placebo in patients with non-erosive gastro-oesophageal reflux disease. Aliment Pharmacol Ther 1996; 10:441.
- Rohof WO, Bennink RJ, Smout AJ, et al. An alginate-antacid formulation localizes to the acid pocket to reduce acid reflux in patients with gastroesophageal reflux disease. Clin Gastroenterol Hepatol 2013; 11:1585.
- Poynard T, Vernisse B, Agostini H. Randomized, multicentre comparison of sodium alginate and cisapride in the symptomatic treatment of uncomplicated gastro-oesophageal reflux. Aliment Pharmacol Ther 1998; 12:159.
- Sweis R, Kaufman E, Anggiansah A, et al. Post-prandial reflux suppression by a raft-forming alginate (Gaviscon Advance) compared to a simple antacid documented by magnetic resonance imaging and pH-impedance monitoring: mechanistic assessment in healthy volunteers and randomised, controlled, double-blind study in reflux patients. Aliment Pharmacol Ther 2013; 37:1093.
- Chiu CT, Hsu CM, Wang CC, et al. Randomised clinical trial: sodium alginate oral suspension is non-inferior to omeprazole in the treatment of patients with non-erosive gastroesophageal disease. Aliment Pharmacol Ther 2013; 38:1054.
- Thomas E, Wade A, Crawford G, et al. Randomised clinical trial: relief of upper gastrointestinal symptoms by an acid pocket-targeting alginate-antacid (Gaviscon Double Action) - a double-blind, placebo-controlled, pilot study in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2014; 39:595.
- Komazawa Y, Adachi K, Mihara T, et al. Tolerance to famotidine and ranitidine treatment after 14 days of administration in healthy subjects without Helicobacter pylori infection. J Gastroenterol Hepatol 2003; 18:678.
- Wolfe MM, Sachs G. Acid suppression: optimizing therapy for gastroduodenal ulcer healing, gastroesophageal reflux disease, and stress-related erosive syndrome. Gastroenterology 2000; 118:S9.
- Kahrilas PJ. Gastroesophageal reflux disease. JAMA 1996; 276:983.
- Sabesin SM, Berlin RG, Humphries TJ, et al. Famotidine relieves symptoms of gastroesophageal reflux disease and heals erosions and ulcerations. Results of a multicenter, placebo-controlled, dose-ranging study. USA Merck Gastroesophageal Reflux Disease Study Group. Arch Intern Med 1991; 151:2394.
- Cloud ML, Offen WW, Robinson M. Nizatidine versus placebo in gastroesophageal reflux disease: a 12-week, multicenter, randomized, double-blind study. Am J Gastroenterol 1991; 86:1735.
- Hunt R. Acid suppression for reflux disease: "off-the-peg" or a tailored approach? Clin Gastroenterol Hepatol 2012; 10:210.
- Ip S, Chung M, Moorthy D, et al. Comparative effectiveness of management strategies for gastroesophageal reflux disease: Update. (Prepared by Tufts Medical Center Evidence-based Practice Center under Contract No. HHSA 290-2007-10055-I.) Rockville, MD: Agency for Healthcare Research and Quality. September 2011. Available at: http://www.effectivehealthcare.ahrq.gov/ehc/products/165/755/CER29-GERD_20110926.pdf.
- Chiba N, De Gara CJ, Wilkinson JM, Hunt RH. Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology 1997; 112:1798.
- Kahrilas PJ, Howden CW, Hughes N. Response of regurgitation to proton pump inhibitor therapy in clinical trials of gastroesophageal reflux disease. Am J Gastroenterol 2011; 106:1419.
- Sigterman KE, van Pinxteren B, Bonis PA, 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 2013; 5:CD002095.
- Chiba N. Proton pump inhibitors in acute healing and maintenance of erosive or worse esophagitis: a systematic overview. Can J Gastroenterol 1997; 11 Suppl B:66B.
- Wang WH, Huang JQ, Zheng GF, et al. Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: a meta-analysis. World J Gastroenterol 2005; 11:4067.
- Fass R, Sifrim D. Management of heartburn not responding to proton pump inhibitors. Gut 2009; 58:295.
- Peura DA, Freston JW, Haber MM, et al. Lansoprazole for long-term maintenance therapy of erosive esophagitis: double-blind comparison with ranitidine. Dig Dis Sci 2009; 54:955.
- Vigneri S, Termini R, Leandro G, et al. A comparison of five maintenance therapies for reflux esophagitis. N Engl J Med 1995; 333:1106.
- Schindlbeck NE, Klauser AG, Berghammer G, et al. Three year follow up of patients with gastrooesophageal reflux disease. Gut 1992; 33:1016.
- Ip S, Bonis P, Tatsioni A, et al. Comparative Effectiveness of Management Strategies for Gastroesophageal Reflux Disease. Evidence Report/Technology Assessment No. 1. (Prepared by Tufts-New England Medical Center. Evidence-based Practice Center under Contract No. 290-02-0022.) Rockville, MD: Agency for Healthcare Research and Quality. December 2005 www.effectivehealthcare.ahrq.gov/reports/final.cfm (Accessed on March 28, 2012).
- Dent J, Yeomans ND, Mackinnon M, et al. Omeprazole v ranitidine for prevention of relapse in reflux oesophagitis. A controlled double blind trial of their efficacy and safety. Gut 1994; 35:590.
- Robinson M, Lanza F, Avner D, Haber M. Effective maintenance treatment of reflux esophagitis with low-dose lansoprazole. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1996; 124:859.
- Tsai HH, Chapman R, Shepherd A, et al. Esomeprazole 20 mg on-demand is more acceptable to patients than continuous lansoprazole 15 mg in the long-term maintenance of endoscopy-negative gastro-oesophageal reflux patients: the COMMAND Study. Aliment Pharmacol Ther 2004; 20:657.
- Hodgkinson R, Glassenberg R, Joyce TH 3rd, et al. Comparison of cimetidine (Tagamet) with antacid for safety and effectiveness in reducing gastric acidity before elective cesarean section. Anesthesiology 1983; 59:86.
- Witter FR, King TM, Blake DA. The effects of chronic gastrointestinal medication on the fetus and neonate. Obstet Gynecol 1981; 58:79S.
- Physician's Desk Reference, 46th ed, Physician's Desk Reference, Oradell, NJ 1992.
- Ranchet G, Gangemi O, Petrone M. Sucralfate in the treatment of gravidic pyrosis. Giornia Italiano de Ostericia Ginecologia 1990; 12:1.
- Larson JD, Patatanian E, Miner PB Jr, et al. Double-blind, placebo-controlled study of ranitidine for gastroesophageal reflux symptoms during pregnancy. Obstet Gynecol 1997; 90:83.
- Gill SK, O'Brien L, Einarson TR, Koren G. The safety of proton pump inhibitors (PPIs) in pregnancy: a meta-analysis. Am J Gastroenterol 2009; 104:1541.
- Pasternak B, Hviid A. Use of proton-pump inhibitors in early pregnancy and the risk of birth defects. N Engl J Med 2010; 363:2114.
- Lalkin A, Loebstein R, Addis A, et al. The safety of omeprazole during pregnancy: a multicenter prospective controlled study. Am J Obstet Gynecol 1998; 179:727.
- Ruigómez A, García Rodríguez LA, Cattaruzzi C, et al. Use of cimetidine, omeprazole, and ranitidine in pregnant women and pregnancy outcomes. Am J Epidemiol 1999; 150:476.
- Diav-Citrin O, Arnon J, Shechtman S, et al. The safety of proton pump inhibitors in pregnancy: a multicentre prospective controlled study. Aliment Pharmacol Ther 2005; 21:269.
- ASGE Standard of Practice Committee, Shergill AK, Ben-Menachem T, et al. Guidelines for endoscopy in pregnant and lactating women. Gastrointest Endosc 2012; 76:18.
- INDICATIONS FOR UPPER ENDOSCOPY
- INITIAL THERAPY
- Mild and intermittent symptoms
- - Lifestyle and dietary modification
- - Antacids
- - Surface agents and alginates
- - Histamine 2 receptor antagonists
- Severe or frequent symptoms or erosive esophagitis
- - Proton pump inhibitors
- - Treatment of Helicobacter pylori infection
- REFRACTORY SYMPTOMS
- MANAGEMENT OF RECURRENT SYMPTOMS AND MAINTENANCE THERAPY
- PREGNANCY AND LACTATION
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS