Gastroenterology

Gastroenterology

Volume 139, Issue 1, July 2010, Pages 7-13.e3
Gastroenterology

Mini-Reviews and Perspectives
Persistent Reflux Symptoms in the Proton Pump Inhibitor Era: The Changing Face of Gastroesophageal Reflux Disease

https://doi.org/10.1053/j.gastro.2010.05.016Get rights and content

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Definition and Epidemiology

Incomplete response of classic GERD symptoms, such as heartburn and regurgitation, to PPI therapy is common. A recent American Gastroenterological Association survey of >1000 subjects receiving PPI therapy for GERD symptoms demonstrated that 38% reported residual symptoms, and that more than half of those with residual symptoms took additional medication to control symptoms, most commonly over-the-counter antacids (47%).4 A systematic review of symptom control in trials of PPI therapy for GERD

Differential Diagnosis of Residual Reflux Symptoms on PPI

When patients have symptoms of ongoing reflux despite maximal PPI therapy, the main clinical question is: Are these symptoms related to gastroesophageal reflux? There is a broad differential diagnosis to consider, and potential etiologies may be gastrointestinal (GI) or non-GI related. The GI etiologies can be esophageal or nonesophageal, and the former may be reflux or non-reflux related. There are 3 major categories of reflux-related causes. First is reflux with ongoing acid exposure.

Mechanisms of Persistent Reflux Symptoms

The putative mechanisms of PPI-refractory GERD symptoms are illustrated in Figure 1. Similar to the differential diagnosis for symptoms, the mechanisms can be either reflux or non-reflux related.

Diagnostic Evaluation of Persistent Symptoms

For patients with esophageal reflux symptoms that persist on PPI therapy, the goal is to determine whether there is reflux disease, what the mechanism might be, and if there is not reflux disease, to perform other appropriate evaluation (Figure 2). After consideration of serious non-GI pathology and ensuring correct medication dosing, upper endoscopy is performed. It is important to recognize the yield of this procedure for structural disease is low, with only 0.2% of patients having esophageal

Therapeutic Options

As noted, the escalation of PPI therapy beyond BID dosing is of unproven utility, and the vast majority of GERD subjects on BID dosing normalize esophageal acid exposures. Although early work suggested that the addition of nighttime H2 receptor antagonists was beneficial,74 follow-up studies demonstrated early tolerance limiting utility,75 and routine administration of nighttime H2 blocker is not recommended.8 Several classes of medications have been proposed as adjunct therapy for subjects

Conclusion

Persistent reflux symptoms in the face of PPI therapy are common in subjects treated for GERD, and most subjects will not demonstrate pathologically elevated acid exposures. Multiple pathophysiologic mechanisms have been proposed to account for these persistent symptoms. The diagnostic evaluation of subjects with persistent reflux symptoms while on PPIs revolves around excluding alternative diagnoses and isolating the likely mechanism(s) of symptoms. A variety of therapeutic modalities are

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Conflicts of interest The authors disclose the following: Nicholas J. Shaheen receives research funding from AstraZeneca, BARRX Medical, CSA Medical, Oncoscope Procter & Gamble, and Takeda, and is a consultant for AstraZeneca, CSA Medical, Oncoscope, and Takeda. Evan S. Dellon receives investigator-initiated research funding from AstraZeneca.

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