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Patients that do not respond satisfactorily to standard proton pump inhibitor (PPI) treatment have become the most common presentation of gastro-esophageal reflux disease (GERD) in third referral gastrointestinal practices. The causes of refractory GERD include lack of compliance with treatment, residual acid reflux and weakly acidic reflux, esophageal hypersensitivity and persistent symptoms not associated with reflux. A role for weakly acidic reflux in symptom generation has been proposed since the availability of impedance-pH monitoring. The possible mechanisms by which persistent weakly acidic reflux might contribute to persistent symptoms in patients under PPI treatment may include esophageal distension by increased reflux volume, persistent impaired mucosal integrity (ie, dilation of intercellular spaces) and/or esophageal hypersensitivity to weakly acidic reflux events. To establish a definite role of weakly acidic reflux in refractory GERD, outcome studies targeting this type of reflux are still lacking. Treatment strategies to reduce the number or effect of weakly acidic reflux could involve drugs that decrease transient lower esophageal sphincter relaxations (ie, baclofen or similar), improve oesophageal mucosa resistance or visceral pain modulators. Finally, anti-reflux surgery can be considered, only if a clear symptom-weakly acidic reflux association was demonstrated.

The Role of Weakly Acidic Reflux in Proton Pump Inhibitor Failure, Has Dust Settled?