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. Author manuscript; available in PMC: 2023 Jan 1.
Published in final edited form as: Am J Gastroenterol. 2022 Jan 1;117(1):27–56. doi: 10.14309/ajg.0000000000001538

Table 2.

Key concept statements

Diagnosis of GERD
 We do not recommend HRM solely as a diagnostic test for GERD.
GERD management
 There is conceptual rationale for a trial of switching PPIs for patients who have not responded to one PPI. For patients who have not responded to one PPI, more than one switch to another PPI cannot be supported.
 Use of the lowest effective dose is recommended and logical but must be individualized. One area of controversy relates to abrupt PPI discontinuation and potential rebound acid hypersecretion, resulting in increased reflux symptoms. Although this has been demonstrated to occur in healthy controls, strong evidence for an increase in symptoms after abrupt PPI withdrawal is lacking.
Extraesophageal GERD
 Although GERD may be a contributor to extraesophageal symptoms in some patients, careful evaluation for other causes should be considered for patients with laryngeal symptoms, chronic cough, and asthma.
 Diagnosis, evaluation, and management of potential extraesophageal symptoms of GERD is limited by lack of a gold-standard test, variable symptoms, and other disorders which may cause similar symptoms
 Endoscopy is not sufficient to confirm or refute the presence of extraesophageal GERD.
 Because of difficulty in distinguishing between patient with laryngeal symptoms and normal controls, salivary pepsin testing is not recommended for evaluation of patients with extraesophageal reflux symptoms
 For patients whose extraesophageal symptoms have not responded to a trial of twice-daily PPIs, we recommend upper endoscopy, ideally off PPIs for 2–4 wk. If endoscopy is normal, consider reflux monitoring. If EGD shows EE, that does not confirm that the extraesophageal symptoms are from GERD. Patients still may need pH-impedance testing
 For patients with extraesophageal symptoms, we do not routinely recommend oropharyngeal or pharyngeal pH monitoring.
Refractory GERD
 It is important to stop PPI therapy in patients whose off-therapy reflux testing is negative, unless another indication for continuing PPIs is present. In 1 study, 42% of patients reported continuing PPI treatment after a negative evaluation for refractory GERD, which included negative endoscopy and pH-impedance monitoring [2].
 Esophageal manometry should be considered as part of the evaluation for patients with refractory GERD in patients with a normal endoscopy and pH monitoring study and for patients being considered for surgical or endoscopic treatment.
 If not already performed off PPIs, we recommend diagnostic upper endoscopy with esophageal biopsies after discontinuing PPI therapy, ideally for 2 to 4 wk
 For patients with PPI-refractory symptoms who have a normal pH monitoring test OFF PPIs or a normal impedance-pH monitoring test ON PPIs (including a negative SI and SAP), we recommend discontinuation of PPIs unless there is an indication for PPI therapy other than the refractory symptoms.
Surgical and endoscopic therapy
 We recommend HRM before antireflux surgery or endoscopic therapy to rule out achalasia and absent contractility. For patients with ineffective esophageal motility, HRM should include provocative testing to identify contractile reserve (e.g., multiple rapid swallows).
 We recommend a careful evaluation and caution before proceeding with invasive therapy for patients with PPI-refractory GERD symptoms other than regurgitation.
 Before performing invasive therapy for GERD, a careful evaluation is required to ensure that GERD is present and as best as possible determine is the cause of the symptoms to be addressed by the therapy, to exclude achalasia (which can be associated with symptoms such as heartburn and regurgitation that can be confused with GERD), and to exclude conditions that might be contraindications to invasive treatment such as absent contractility.
Long-term PPI issues
 Regarding the safety of long-term PPI usage for GERD, we suggest that patients should be advised as follows: “PPIs are the most effective medical treatment for GERD. Some medical studies have identified an association between the long-term use of PPIs and the development of numerous adverse conditions including intestinal infections, pneumonia, stomach cancer, osteoporosis-related bone fractures, chronic kidney disease, deficiencies of certain vitamins and minerals, heart attacks, strokes, dementia, and early death. Those studies have flaws, are not considered definitive, and do not establish a cause-and-effect relationship between PPIs and the adverse conditions. High-quality studies have found that PPIs do not significantly increase the risk of any of these conditions except intestinal infections. Nevertheless, we cannot exclude the possibility that PPIs might confer a small increase in the risk of developing these adverse conditions. For the treatment of GERD, gastroenterologists generally agree that the well-established benefits of PPIs far outweigh their theoretical risks.”
 Switching PPIs can be considered for patients who experience minor PPI side effects including headache, abdominal pain, nausea, vomiting, diarrhea, constipation, and flatulence.
 For patients with GERD on PPIs who have no other risk factors for bone disease, we do not recommend that they raise their intake of calcium or vitamin D or that they have routine monitoring of bone mineral density.
 For patients with GERD on PPIs who have no other risk factors for vitamin B12 deficiency, we do not recommend that they raise their intake of vitamin B12 or that they have routine monitoring of serum B12 levels.
 For patients with GERD on PPIs who have no other risk factors for kidney disease, we do not recommend that they have routine monitoring of serum creatinine levels.
 For patients with GERD on clopidogrel who have LA grade C or D esophagitis or whose GERD symptoms are not adequately controlled with alternative medical therapies, the highest quality data available suggest that the established benefits of PPI treatment outweigh their proposed but highly questionable cardiovascular risks.
 PPIs can be used to treat GERD in patients with renal insufficiency with close monitoring of renal function or consultation with a nephrologist.

EE, erosive esophagitis; GERD, gastroesophageal reflux disease; HRM, high-resolution manometry; LA, Los Angeles; PPI, proton pump inhibitor; SAP, symptom association probability; SI, symptom index.