Drugs

, Volume 69, Issue 14, pp 1935–1944

Refractory Gastro-Oesophageal Reflux Disease

Diagnosis and Management
Therapy in Practice

Abstract

Refractory gastro-oesophageal reflux disease (GORD) is described when reflux symptoms have not responded to 4–8 weeks of proton pump inhibitor therapy and occurs in a heterogeneous mixture of patients. The causes of refractory GORD include inadequate acid suppression, non-acid gastro-oesophageal reflux, and non-reflux causes of GORD symptoms including achalasia, gastroparesis and functional heartburn. Upper gastrointestinal tract endoscopy should initially be performed to identify the presence of oesophagitis, and exclude other diagnoses including eosinophilic oesophagitis and peptic ulcer disease. Patients with refractory symptoms but with a normal upper endoscopy are more difficult to diagnose and may require ambulatory pH monitoring, impedance testing, oesophageal motility tests and gastric emptying scans. The primary goal of treatment is symptom reduction and eventual elimination, which can be achieved with proper identification of the underlying cause of the symptoms.

References

  1. 1.
    Sandler RS, Everhart JE, Donowitz M, et al. The burden of selected digestive diseases in the United States. Gastroenterology 2002; 122(5): 500–11CrossRefGoogle Scholar
  2. 2.
    Dent J, El-Serag HB, Wallander MA, et al. Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 2005 May; 54(5): 710–7PubMedCrossRefGoogle Scholar
  3. 3.
    Lagergren J, Bergstrom R, Lindgren A, et al. Symptomatic gastroesophageal reflux is a strong risk factor for esophageal adenocarcinoma. N Engl J Med 1999; 340: 825–31PubMedCrossRefGoogle Scholar
  4. 4.
    Shaheen NJ. Advances in Barrett’s esophagus and esophageal adenocarcinoma. Gastroenterology 2005 May; 128(6): 1554–66PubMedCrossRefGoogle Scholar
  5. 5.
    Dent J, Dodds WJ, Friedman RH, et al. Mechanism of gastroesophageal reflux in recumbent asymptomatic human subjects. J Clin Invest 1980 Feb; 65(2): 256–67PubMedCrossRefGoogle Scholar
  6. 6.
    Dodds WJ, Dent J, Hogan WJ, et al. Mechanisms of gas-troesophageal reflux in patients with reflux esophagitis. N Engl J Med 1982 Dec 16; 307(25): 1547–52PubMedCrossRefGoogle Scholar
  7. 7.
    Richter JE. How to manage refractory GERD. Nat Clin Pract Gastroenterol Hepatol 2007 Dec; 4(12): 658–64PubMedCrossRefGoogle Scholar
  8. 8.
    Fass R, Sifrim D. Management of heartburn not responding to proton pump inhibitors. Gut 2009 Feb; 58(2): 295–309PubMedCrossRefGoogle Scholar
  9. 9.
    Bardhan KD. The role of proton pump inhibitors in the treatment of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 1995; 9 Suppl. 1: 15–25PubMedGoogle Scholar
  10. 10.
    Martinez SD, Malagon IB, Garewal HS, et al. Non-erosive reflux disease (NERD): acid reflux and symptom patterns. Aliment Pharmacol Ther 2003 Feb 15; 17(4): 537–45PubMedCrossRefGoogle Scholar
  11. 11.
    Crawley JA, Schmitt CM. How satisfied are chronic heartburn sufferers with their prescription medications? Results of the patient unmet needs survey. J Clin Outcomes Manage 2000; 7(11): 29–34Google Scholar
  12. 12.
    Kahrilas PJ, Shaheen NJ, Vaezi MF. American Gastro-enterological Association Institute technical review on the management of gastroesophageal reflux disease. Gastro-enterology 2008 Oct; 135(4): 1392–413, 413 e1-5CrossRefGoogle Scholar
  13. 13.
    Vakil N, Moayyedi P, Fennerty MB, et al. Limited value of alarm features in the diagnosis of upper gastrointestinal malignancy: systematic review and meta-analysis. Gastro-enterology 2006 Aug; 131(2): 390–401; quiz 659–60CrossRefGoogle Scholar
  14. 14.
    Barrison AF, Jarboe LA, Weinberg BM, et al. Patterns of proton pump inhibitor use in clinical practice. Am J Med 2001 Oct 15; 111(6): 469–73PubMedCrossRefGoogle Scholar
  15. 15.
    Gallup study of consumers’ use of stomach relief products. Princeton (NJ): The Gallup Organization, 2000Google Scholar
  16. 16.
    Sgouros SN, Mantides A. Refractory heartburn to proton pump inhibitors: epidemiology, etiology and management. Digestion 2006; 73(4): 218–27PubMedCrossRefGoogle Scholar
  17. 17.
    Gupte AR, Draganov PV. Eosinophilic esophagitis. World J Gastroenterol 2009 Jan 7; 15(1): 17–24PubMedCrossRefGoogle Scholar
  18. 18.
    Abid S, Mumtaz K, Jafri W, et al. Pill-induced esophageal injury: endoscopic features and clinical outcomes. Endoscopy 2005 Aug; 37(8): 740–4PubMedCrossRefGoogle Scholar
  19. 19.
    Richter JE. The patient with refractory gastroesophageal reflux disease. Dis Esophagus 2006; 19(6): 443–7PubMedCrossRefGoogle Scholar
  20. 20.
    Keate RF, Williams JW, Connolly SM. Lichen planus esophagitis: report of three patients treated with oral tacrolimus or intraesophageal corticosteroid injections or both. Dis Esophagus 2003; 16(1): 47–53PubMedCrossRefGoogle Scholar
  21. 21.
    Hirschowitz BI, Simmons JL, Johnson LF, et al. Risk factors for esophagitis in extreme acid hypersecretors with and without Zollinger-Ellison syndrome. Clin Gastroenterol Hepatol 2004 Mar; 2(3): 220–9PubMedCrossRefGoogle Scholar
  22. 22.
    Furuta T, Shirai N, Sugimoto M, et al. Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies. Drug Metab Pharmacokinet 2005 Jun; 20(3): 153–67PubMedCrossRefGoogle Scholar
  23. 23.
    Turner BG, Saltzman JR, Hua L, et al. Endoscopic pH monitoring for patients with suspected or refractory gastroesophageal reflux disease. Can J Gastroenterol 2007 Nov; 21(11): 737–41PubMedGoogle Scholar
  24. 24.
    Mainie I, Tutuian R, Shay S, et al. Acid and non-acid reflux in patients with persistent symptoms despite acid suppres-sive therapy: a multicentre study using combined ambulatory impedance-pH monitoring. Gut 2006 Oct; 55(10): 1398–402PubMedCrossRefGoogle Scholar
  25. 25.
    Zerbib F, Roman S, Ropert A, et al. Esophageal pH-impedance monitoring and symptom analysis in GERD: a study in patients off and on therapy. Am J Gastroenterol 2006 Sep; 101(9): 1956–63PubMedCrossRefGoogle Scholar
  26. 26.
    Fass R, Murthy U, Hayden CW, et al. Omeprazole 40 mg once a day is equally effective as lansoprazole 30 mg twice a day in symptom control of patients with gastro-oesophageal reflux disease (GERD) who are resistant to conventional-dose lansoprazole therapy: a prospective, randomized, multi-centre study. Aliment Pharmacol Ther 2000 Dec; 14(12): 1595–603PubMedCrossRefGoogle Scholar
  27. 27.
    Brillantino A, Monaco L, Schettino M, et al. Prevalence of pathological duodenogastric reflux and the relationship between duodenogastric and duodenogastrooesophageal reflux in chronic gastrooesophageal reflux disease. Eur J Gastroenterol Hepatol 2008 Dec; 20(12): 1136–43PubMedCrossRefGoogle Scholar
  28. 28.
    Hoffman I, Tertychnyy A, Ectors N, et al. Duodenogastro-esophageal reflux in children with refractory gastroesophageal reflux disease. J Pediatr 2007 Sep; 151(3): 307–11PubMedCrossRefGoogle Scholar
  29. 29.
    Burke CA, Achkar E, Falk GW. Effect of pneumatic dilation on gastroesophageal reflux in achalasia. Dig Dis Sci 1997 May; 42(5): 998–1002PubMedCrossRefGoogle Scholar
  30. 30.
    Jacobson BC, Somers SC, Fuchs CS, et al. Body-mass index and symptoms of gastroesophageal reflux in women. N Engl J Med 2006 Jun 1; 354(22): 2340–8PubMedCrossRefGoogle Scholar
  31. 31.
    An evidence-based appraisal of reflux disease management: the Genval Workshop Report. Gut 1999; 44 Suppl. 2: S1-16Google Scholar
  32. 32.
    Fackler WK, Ours TM, Vaezi MF, et al. Long-term effect of H2RA therapy on nocturnal gastric acid breakthrough. Gastroenterology 2002 Mar; 122(3): 625–32PubMedCrossRefGoogle Scholar
  33. 33.
    Katz PO, Anderson C, Khoury R, et al. Gastro-oesophageal reflux associated with nocturnal gastric acid breakthrough on proton pump inhibitors. Aliment Pharmacol Ther 1998 Dec; 12(12): 1231–4PubMedCrossRefGoogle Scholar
  34. 34.
    Koek GH, Sifrim D, Lerut T, et al. Effect of the GABA(B) agonist baclofen in patients with symptoms and duodeno-gastro-oesophageal reflux refractory to proton pump inhibitors. Gut 2003 Oct; 52(10): 1397–402PubMedCrossRefGoogle Scholar
  35. 35.
    Connor F. Gastrointestinal complications of fundoplication. Curr Gastroenterol Rep 2005 Jun; 7(3): 219–26PubMedCrossRefGoogle Scholar
  36. 36.
    Peters JH, DeMeester TR, Crookes P, et al. The treatment of gastroesophageal reflux disease with laparoscopic Nissen fundoplication: prospective evaluation of 100 patients with “typical” symptoms. Ann Surg 1998; 228(1): 40–50PubMedCrossRefGoogle Scholar
  37. 37.
    DeMeester TR, Bonavina L, Albertucci M. Nissen fundoplication for gastroesophageal reflux disease: evaluation of primary repair in 100 consecutive patients. Ann Surg 1986; 204(1): 9–20PubMedCrossRefGoogle Scholar
  38. 38.
    Bittner HB, Meyers WC, Brazer SR, et al. Laparoscopic Nissen fundoplication: operative results and short-term follow-up. Am J Surg 1994 Jan; 167(1): 193–8; discussion 9–200PubMedCrossRefGoogle Scholar
  39. 39.
    Collard JM, de Gheldere CA, De Kock M, et al. Laparoscopic antireflux surgery: what is real progress? Ann Surg 1994 Aug; 220(2): 146–54PubMedCrossRefGoogle Scholar
  40. 40.
    Walker SJ, Baxter ST, Morris AI, et al. Review article: controversy in the therapy of gastro-oesophageal reflux disease. Long-term proton pump inhibition or laparoscopic anti-reflux surgery? Aliment Pharmacol Ther 1997 Apr; 11(2): 249–60PubMedGoogle Scholar
  41. 41.
    Swoger J, Ponsky J, Hicks DM, et al. Surgical fundoplication in laryngopharyngeal reflux unresponsive to aggressive acid suppression: a controlled study. Clin Gastroenterol Hepatol 2006 Apr; 4(4): 433–41PubMedCrossRefGoogle Scholar
  42. 42.
    Mathew G, Watson DI, Myers JC, et al. Oesophageal motility before and after laparoscopic Nissen fundoplication. Br J Surg 1997 Oct; 84(10): 1465–9PubMedCrossRefGoogle Scholar
  43. 43.
    Jamieson GG, Watson DI, Britten-Jones R, et al. Laparoscopic Nissen fundoplication. Ann Surg 1994 Aug; 220(2): 137–45PubMedCrossRefGoogle Scholar
  44. 44.
    Vakil N, Shaw M, Kirby R. Clinical effectiveness of laparoscopic fundoplication in a U.S. community [comment]. Am J Med 2003; 114(1): 1–5PubMedCrossRefGoogle Scholar
  45. 45.
    Watson DI, Jamieson GG, Baigrie RJ, et al. Laparoscopic surgery for gastro-oesophageal reflux: beyond the learning curve. Br J Surg 1996 Sep; 83(9): 1284–7PubMedCrossRefGoogle Scholar
  46. 46.
    Triadafilopoulos G, Dibaise JK, Nostrant TT, et al. Radiofrequency energy delivery to the gastroesophageal junction for the treatment of GERD. Gastrointest Endosc 2001; 53(4): 407–15PubMedCrossRefGoogle Scholar
  47. 47.
    Filipi CJ, Lehman GA, Rothstein RI, et al. Transoral, flexible endoscopic suturing for treatment of GERD: a multicenter trial. Gastrointest Endosc 2001 Apr; 53(4): 416–22PubMedCrossRefGoogle Scholar
  48. 48.
    Deviere J, Costamagna G, Neuhaus H, et al. Nonresorbable copolymer implantation for gastroesophageal reflux disease: a randomized sham-controlled multicenter trial. Gastroenterology 2005 Mar; 128(3): 532–40PubMedCrossRefGoogle Scholar
  49. 49.
    Liu JJ, Carr-Locke DL, Lee LS, et al. Endoluminal gastro-plication for treatment of patients with classic gastroesophageal reflux symptoms and borderline 24-h pH studies. Scand J Gastroenterol 2004 Jul; 39(7): 615–20PubMedCrossRefGoogle Scholar
  50. 50.
    Chen YK, Raijman I, Ben-Menachem T, et al. Long-term outcomes of endoluminal gastroplication: a U.S. multicenter trial. Gastrointest Endosc 2005 Jun; 61(6): 659–67PubMedCrossRefGoogle Scholar
  51. 51.
    Rothstein RI, Pohl H, Grove M, et al. Endoscopic gastric plication for the treatment of GERD: two year follow-up results [abstract]. Am J Gastroenterol 2001; 96 (9 Suppl.): S35CrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.Division of Gastroenterology, Department of MedicineUniversity of AlbertaEdmontonCanada
  2. 2.Gastroenterology DivisionBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA

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