What are the management options for patients with refractory Gastroesophageal Reflux Disease (GERD)?

From the Guidelines

Patients with refractory Gastroesophageal Reflux Disease (GERD) should be managed with a stepwise approach, starting with optimization of proton pump inhibitor (PPI) therapy, addition of adjunctive medications, and lifestyle modifications, as recommended by the most recent guidelines 1.

Management Options

The management of refractory GERD involves:

• Optimization of PPI therapy, with medications like omeprazole 40mg, esomeprazole 40mg, or pantoprazole 40mg 30-60 minutes before meals, with twice-daily dosing often providing better symptom control than once-daily regimens 1
• Addition of adjunctive medications, such as H2 receptor antagonists (e.g., famotidine 20-40mg at bedtime), prokinetics (e.g., metoclopramide 5-10mg before meals), alginates, and baclofen (5-20mg three times daily) for refractory regurgitation 1
• Lifestyle modifications, including weight loss, elevation of the head of the bed by 6-8 inches, avoiding meals 2-3 hours before bedtime, and eliminating trigger foods, as suggested by the AGA clinical practice update 1

Surgical Interventions

For patients who fail medical therapy, surgical options include:

• Laparoscopic Nissen fundoplication, which creates a 360-degree wrap around the lower esophageal sphincter
• Less invasive procedures like the LINX device (magnetic beads that reinforce the sphincter) or TIF (Transoral Incisionless Fundoplication) 1

Alternative Diagnoses

Refractory GERD should prompt consideration of alternative diagnoses, such as achalasia, eosinophilic esophagitis, or functional heartburn, which may require specific diagnostic tests like impedance-pH monitoring, high-resolution manometry, or endoscopy with biopsies 1

Key Considerations

• A precision approach to escalation of management is suggested for patients with ongoing symptoms despite initial measures, driven by factors such as integrity of the anti-reflux barrier, presence of visceral hypersensitivity and hypervigilance, confirmation of PPI refractory-GERD, symptom profile, body mass index, and esophageal (as well as gastric) motor function 1
• Patients with non-severe GERD often respond well to optimization of lifestyle and pharmacotherapy, and may ultimately be able to wean pharmacotherapy down to the lowest effective dose, unless erosive reflux disease or Barrett’s esophagus exists 1

From the FDA Drug Label

Metoclopramide tablets, USP are a prescription medicine used: • in adults for 4 to 12 weeks to relieve heartburn symptoms with gastroesophageal reflux disease (GERD) when certain other treatments do not work.

The management options for patients with refractory Gastroesophageal Reflux Disease (GERD) include metoclopramide tablets, USP for 4 to 12 weeks to relieve heartburn symptoms when certain other treatments do not work 2. Key points:

• Metoclopramide tablets, USP relieve daytime heartburn and heartburn after meals.
• They also help ulcers in the esophagus to heal.
• The treatment with metoclopramide should not exceed 12 weeks 2.

From the Research

Diagnosis of Refractory GERD

• Refractory GERD is defined as the preservation of typical symptoms of the disease and/or incomplete healing of the esophageal mucosa against the background of taking a standard dose of proton pump inhibitors (PPI) once a day for 8 weeks 3
• The definition of refractory GERD is a controversial topic, and some patients unresponsive to PPIs who experience symptoms potentially related to GERD may not have GERD 4
• Diagnostic approaches include x-ray examination of the esophagus and stomach, endoscopy with biopsy, 24-hour Impedance-pH monitoring, and esophageal manometry 3

Management Options for Refractory GERD

• Management strategies include a careful check of patient's compliance with PPIs, a possible change in the timing of their administration, and the choice of a PPI with a different metabolic pathway 4
• Other pharmacologic treatments include histamine-2 receptor antagonists (H2RAs), alginates, antacids, and mucosal protective agents, potassium competitive acid blockers (PCABs), prokinetics, gamma aminobutyric acid-B (GABA-B) receptor agonists, and metabotropic glutamate receptor-5 (mGluR5) antagonists, and pain modulators 4
• If there is no benefit from medical therapy, but there is objective evidence of GERD, invasive antireflux options should be evaluated, including laparoscopic antireflux surgery (LARS), endoscopic transoral incisionless fundoplication (TIF), magnetic sphincter augmentation (LINX), or radiofrequency therapy (Stretta) 4
• Switching to esomeprazole could be used to improve symptoms and quality of life in patients with refractory GERD 5

Treatment Approaches

• Lifestyle changes, doubling the dose of PPI, replacing PPI with another, adding H2-receptor antagonists, prokinetics, antacids, alginates, and adsorbents may be considered depending on the reasons for the lack of response to therapy 3
• Simple advice and minor adjustments to medical therapy are usually all that is needed for most patients, but in some, management requires knowledge of the principles outlined in the literature 6
• Patients experiencing complete response to PPIs do not usually need further management, while patients with partial response can be treated surgically or by using emerging endoscopic therapies 7