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Clinical manifestations, diagnosis, and treatment of non-acid reflux

Radu Tutuian, MD
Donald O Castell, MD
Section Editor
Nicholas J Talley, MD, PhD
Deputy Editor
Shilpa Grover, MD, MPH, AGAF


Persistent symptoms in patients with suspected gastroesophageal reflux disease (GERD) who have been treated with proton pump inhibitors (PPIs) can be due to a variety of causes. A subset of these patients has symptoms related to continued reflux of non-acidic material. Advances in technology to evaluate esophageal function have clarified the role of non-acid reflux in the pathogenesis of persistent esophageal symptoms. Two developments have converged over the past 25 years to unmask the presence and prevalence of non-acid GERD symptoms. The availability of proton pump inhibitors in the late 1980s provided the opportunity to achieve maximal acid suppression. The development of ambulatory combined impedance-pH monitoring allowed identification of acid and non-acid reflux episodes and their temporal relation to symptoms.

This topic review will summarize the clinical importance of non-acid reflux. A general approach to patients with suspected GERD who have persistent symptoms after taking PPIs is presented separately. (See "Approach to refractory gastroesophageal reflux disease in adults".)


Gastroesophageal reflux (GER) represents the retrograde flow of gastric content into the esophagus. It occurs even in healthy individuals and is regarded as "physiologic" as long as it does not induce esophageal mucosal abnormalities or symptoms.

Acid reflux is defined as the reflux of gastric contents with a pH <4.0. Non-acid reflux is reflux of gastric contents with a pH >4.0 (ie, above the threshold used by conventional pH monitoring to identify acid reflux).

Experts have suggested a new definition of GER episodes that defines reflux with a pH of 4.0 to 7.0 as "weakly acidic" reflux, and GER with a pH above 7.0 "weakly alkaline" [1]. However, given the low prevalence of "weakly alkaline" reflux episodes we separate GER episodes into acid and non-acid using a cutoff value of 4.0, thereby grouping "weakly acidic" and "weakly alkaline" reflux into "non-acid" reflux.

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Literature review current through: Nov 2017. | This topic last updated: Dec 17, 2015.
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