Evaluation and Management of Patients with PPI-Refractory Heartburn

Abstract

To use recent insights on the causes and treatment of PPI-refractory heartburn to formulate an effective approach to patient management. PPI-refractory heartburn results from 5 major potential mechanisms: (1) PPIs have not normalized esophageal acid exposure; (2) PPIs have normalized esophageal acid exposure, but there is reflux hypersensitivity in which persistent “physiologic” reflux events evoke heartburn; (3) the sensation of heartburn is caused by an esophageal disorder other than GERD (e.g., eosinophilic esophagitis, achalasia); (4) the sensation of heartburn is caused by an extra-esophageal disorder (e.g., heart disease, pancreaticobiliary disease); or (5) heartburn is functional. A systematic work-up that includes careful medical history, endoscopy with esophageal biopsy, esophageal manometry, and esophageal impedance-pH monitoring can distinguish among these mechanisms. A systematic work-up will reveal that GERD is not the cause of PPI-refractory heartburn in the large majority of cases. In the minority of patients for whom the work-up establishes that PPI-refractory heartburn is reflux-related, however, antireflux surgery is superior to medical therapy.