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When PPIs Don't Work: What's Next in Reflux Management?

When PPIs Don't Work: What's Next in Reflux Management?

© PathDoc/© PathDoc/

Gastroesophageal reflux disease (GERD) is one of the most common diseases seen in primary care practice. The most common presenting symptoms include heartburn, regurgitation and difficulty swallowing (dysphagia). The disease is often treated empirically with proton pump inhibitors (PPI) since the diagnosis is clinical. However, when a patient does not respond to either once or twice daily PPI therapy, should we consider refractory GERD?

Dr Philip Katz, interim chair, department of medicine, chair, division of gastroenterology, Einstein Medical Center, Philadelphia, Pa, who spoke on the topic of what to consider when PPI treatment isn’t enough at the 2015 American College of Gastronenterology Scientific Meeting, suggested asking a few fundamental clinical questions before referring to your friendly neighborhood gastroenterologist:

 ► Why is the patient still symptomatic after traditional treatment?

 ► Is acid suppression optimized, that is, by appropriate dosing and timing?

 ► Does the patient have reflux that may be weakly acidic and therefore less amenable to PPI therapy  ie when the esophageal pH falls by ≥1 unit, but remains >4, it is considered weakly acidic reflux which has been associated with PPI-refractory GERD) or do they have physiologic reflux that they sense (ie esophageal hypersensitivity).

Typically, if the diagnosis of GERD is correct, a patient will receive some benefit with PPI therapy. Before searching for alternative diagnoses important to ensure that the patient is taking the medication correctly. Optimal PPI ingestion should be at least 30 minutes to an hour prior to food intake (capsules should not be opened, chewed, or crushed!) and all PPIs have similar efficacy.  PPIs provide superior acid suppression in comparison to H2 blockers.

If medication is being taken appropriately, alternative diagnoses can be entertained (rumination, aerophagia, achalasia, functional heartburn or chest pain, gastroparesis, eosinophilic esophagitis as examples) and an endoscopy should be performed. If a patient has refractory GERD, there will be evidence on endoscopy (erosive esophagitis or Barrett’s esophagus). However, if nothing is found on endoscopy, the patient should have pH monitoring to prove that the symptoms correlate with episodes of reflux and expected drops in esophageal pH. 

Should you stop the PPI before endoscopy? If there is a low pretest probability of GERD, test off the medication (7-10 days). However, if you have a high pretest probability of GERD, test on the PPI medication. If reflux monitoring (pH testing) is negative, the PPI can be stopped.

If pH monitoring validates acid reflux, and if PPI therapy and timing are optimized, surgical and pharmacologic options remain. Baclofen may offer potential salvage therapy (no placebo controlled trials yet). Alternatively, endoscopic options include radiofrequency ablation of the lower esophageal sphincter (in observational studies it has been shown to improve symptoms). Surgical candidates can consider transoral incisional fundoplication. It has been shown to significantly improve symptoms and reduce regurgitation in placebo controlled trials.

Magnetic sphincter augmentation directed at the lower esophageal sphincter—laparoscopically-implanted magnetized beads that are removable—has improved endpoints of heartburn, regurgitation, and PPI dependence.

If your patient does not get relief from a PPI, all is not lost. If symptoms persist and PPIs are being taken correctly, use endoscopy and Bravo pH monitoring (if endoscopy is negative). An individualized approach incorporating newer technologies may offer relief.   


Katz P. Approach to patients with continued symptoms on a PPI. Presentation at: 2015 American College of Gastroenterology Scientific Session; October 17, 2015;Honolulu, Hawaii.    

Katz PO, Gerson LB, Vela M. Guidelines for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol 2013; 108:308–328.

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