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PPI Refractory Gastroesophageal Reflux Disease

10/8/2022 6:02:35 PM

Diagnosis of PPI refractory GERD requires the presence of troublesome symptoms and 
objective evidence of ongoing pathologic GERD despite PPI optimization. pH-impedance 
monitoring on PPI therapy is the standard method to objectively document PPI refractory 
GERD. Alternate causes of PPI non-response are common and should be ruled out to avoid 
misdiagnosis and mismanagement. Mechanisms of PPI refractory GERD vary and include a 
dysfunction of protective systems (e.g., anti-reflux barrier, esophageal clearance, epithelial 
resistance) and enhanced reflux physiology (e.g., TLESR episodes, hypotensive LES with 
free-or strain induced reflux, re-reflux with hiatal hernia).
As such, management of PPI refractory GERD should be tailored to mechanism, patient 
profile, and patient preference, as possible. It is reasonable to switch PPIs from CYP 
dependent to less CYP dependent PPIs (e.g., rabeprazole, esomeprazole). H2RAs may be an option for patients reporting nighttime symptoms and/or in the setting of breakthrough 
nocturnal acid exposure. P-CABs seem to be a promising pharmacologic option for acid 
related erosive disease, however are not currently available in the US. GABA agonists such 
as Baclofen may be tried in PPI refractory GERD, particularly in patients exhibiting 
TLESRs, an elevated number of reflux events, and regurgitation; GABA agonists may not be 
as effective in the setting of hiatal hernia. Alginate-antacids carry a favorable safety profile 
and may be an effective adjunct to PPI.
When non-invasive treatment options fail, invasive anti-reflux options should be considered. 
Once again, confirmation of objective PPI refractory GERD is essential as surgical and 
endoscopic anti-reflux interventions are associated with risks, and outcomes are dependent 
on appropriate patient selection. The gold standard anti-reflux surgery remains laparoscopic 
fundoplication in the form of a complete or partial wrap. Other interventions include 
laparoscopic magnetic sphincter augmentation, endoscopic transoral incisionless 
fundoplication, or endoscopic radiofrequency energy delivery to the LES. Selection of antireflux intervention requires a discussion of risks and long-term efficacy and durability with 
the patient.

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