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Refractory Gastroesophageal Reflux Disease
Refractory gastroesophageal reflux disease is the persistence of troublesome gastroesophageal reflux disease symptoms in compliant patients despite standard treatment or twice-daily dosing of proton pump inhibitor for at least 8 weeks. The troublesome symptoms impair the patient's quality of life and may cause sleep disturbance and affect work. Patients with non-erosive reflux disease commonly have PPI-resistant gastroesophageal reflux disease symptoms. The causes include inadequate acid suppression, weakly acidic/non-acidic reflux, reflux sensitivity or other non-reflux causes such as functional heartburn, dysmotility, and eosinophilic esophagitis or overlap syndrome with IBS and visceral hypersensitivity. The impaired proton pump inhibitor treatment response may also be related to increased body weight and P450 system genotypes which affect proton pump inhibitor metabolism. Further evaluation may be considered in proton pump inhibitor therapy non-responders and may include an upper GI endoscopy with or without enhanced imaging and function testing (ambulatory pH monitoring and 24-hour combined impedance-pH studies/esophageal manometry). Patients with suspected extraesophageal symptoms and who have failed proton pump inhibitor therapy should be evaluated for non-GERD causes prior to starting GI evaluation with endoscopy or function testing. Therapeutic options to consider include increasing the proton pump inhibitor dose, switching to a different proton pump inhibitor or potassium-competitive acid blocker, doubling the potassium-competitive acid blocker dose, changing medication time, or adding a prokinetic agent, an alginate or an H2RA at night.