Proton-pump inhibitor failure/resistance: Proposed mechanisms and therapeutic algorithm

Abstract

Proton-pump inhibitor (PPI) failure has become more prevalent with the increasing use of PPI as the first-line agent in the treatment of gastroesophageal reflux disease (GERD). The underlying mechanisms are diverse and may overlap. The commonly available investigations are limited in their capacity in identifying the underlying cause for PPI failure. Multichannel intraluminal impedance with 24-h pH sensors may be useful to identify non-acid or duodenogastroesophageal reflux in selected cases. The management strategy for PPI failure is largely empirical. Patients who have symptomatic failure on normal dose of PPI shall try double dose PPI. Failing that, empirical treatment with transient lower esophageal sphincter relaxation reducers or pain modulators can be tried. Better understanding of the pathophysiology and mechanisms for PPI failure will help to improve the management of this rising problem. © 2006 The Authors.