Official websites use. Share sensitive information only on official, secure websites. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. The evaluation should start with a symptom assessment and may progress to imaging, endoscopy, and monitoring of esophageal pH, impedance, and bilirubin. There are a variety of pharmacologic and procedural interventions that should be selected based on the underlying mechanism of PPI failure.
Pharmacologic treatments can include antacids, prokinetics, alginates, bile acid binders, reflux inhibitors, and antidepressants. Procedural options include laparoscopic fundoplication and LINX as well as endoscopic procedures, such as transoral incisionless fundoplication and Stretta.
Several alternative and complementary treatments of possible benefit also exist. Gastroesophageal reflux disease GERD , the most common upper gastrointestinal GI disorder in the US, 1 is defined as symptoms or lesions that result from the retrograde flow of gastric contents into the esophagus.
Chemically, all PPIs consist of a benzimidazole ring and a pyridine ring but vary in side ring substitution. Patients with continued symptoms despite PPI treatment are considered to have refractory GERD, which is generally defined as the persistence of typical symptoms that do not respond to stable, twice-daily PPI dosing during at least 12 weeks of treatment. There are many potential causes of refractory GERD that vary in incidence, clinical importance, and symptom severity and frequency.
Poor compliance and adherence should first be assessed before further evaluation is pursued. The most common mechanisms for refractory GERD include functional bowel disorders, weakly acidic reflux, and residual acid. Factors related to metabolism and bioavailability play a limited role in PPI failure. GERD-like symptoms may also be due to a variety of other disorders, such as eosinophilic esophagitis EoE , pill-induced esophagitis, infectious esophagitis, and achalasia, which should be considered in the differential diagnosis of patients with unremitting symptoms Table 1.
