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Diagnosis and management of patients with reflux symptoms refractory to proton pump inhibitors
  1. Daniel Sifrim1,
  2. Frank Zerbib2
  1. 1Wingate Institute of Neurogastroenterology, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  2. 2Gastroenterology and Hepatology Department, Saint André Hospital, Centre Hospitalier Universitaire de Bordeaux; Université Bordeaux Segalen, Bordeaux, France
  1. Correspondence to Professor Dr Daniel Sifrim, The Wingate Institute of Neurogastroenterology, 26 Ashfield Street, London E1 2AJ, UK; d.sifrim{at}


Approximately a third of patients with suspected gastro-oesophageal reflux disease are resistant or partial responders to proton pump inhibitors (PPIs). Many of these patients do not have gastro-oesophageal reflux disease, but suffer from functional heartburn or dyspepsia. The potential mechanisms underlying failure of PPI treatment in patients with reflux-related symptoms include persistence of isolated or mixed acid, weakly acidic, bile or gas reflux, impaired oesophageal mucosal integrity, chemical or mechanical hypersensitivity to refluxates and psychological comorbidity. After thorough clinical evaluation and failure of empirical changes in PPI dose regime, diagnostic investigations include endoscopy and reflux monitoring with pH or pH-impedance monitoring. If symptoms are clearly related to persistent reflux, baclofen, antireflux surgery or pain modulators can be considered. If not, pain modulators are the only currently available therapy.

  • Gastro-oesophageal reflux
  • proton pump inhibitors
  • oesophageal impedance
  • functional digestive disorders
  • gastrointestinal motility
  • dysphagia
  • erosive oesophagitis
  • mucosal barrier
  • neurogastroenterology
  • gastro-oesophageal reflux disease
  • oesophageal motility
  • antireflux therapy
  • gastro-oesophageal junction

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  • Competing interests Daniel Sifrim has served as a speaker, consultant and advisory board member for Sandhill Scientific, MMS, Xenoport, Shire Movetis, AstraZeneca, Janssen Cilag, Reckitt Benckiser, Pfizer, Novartis and GlaxoSmithKline. Frank Zerbib has served as a speaker, consultant and advisory board member for Addex Pharma SA, Xenoport, Shire Movetis, Norgine, Sanofi Aventis, AstraZeneca, Janssen Cilag, Reckitt Benckiser, Abbott, Pfizer and Given Imaging.

  • Provenance and peer review Commissioned; externally peer reviewed.