Reflux esophagitis: What will your doctor do if an antacid (PPI) fails? (Part 2)

Posted by Master, Doctor Mai Vien Phuong - Department of Examination & Internal Medicine - Vinmec Central Park International General Hospital

Before a patient is diagnosed with refractory reflux esophagitis, the clinician will re-test the diagnosis, assess the cause of why PPIs are not working for the patient, and then reevaluate treatment-resistant GERD. with the subclinical. Several diagnostic modalities are available to evaluate patients who have failed PPI therapy.

The appropriate treatment for patients with refractory reflux esophagitis who fail to receive a once-daily PPI is not well defined in the literature. The commonly used approach, which has become the standard of care in clinical practice, is to double the PPI dose. Hetzel et al. compared the curative effects of omeprazole 20 mg once daily versus 40 mg once daily in patients with erosive esophagitis for an 8-week period.
The authors demonstrated that by doubling the PPI dose, esophageal wound healing was only improved by 6%. Interestingly, an additional 4 weeks of treatment resulted in further, albeit very limited, improvement in esophageal healing. Levels of symptom improvement were not reported in this study, but the authors found that patients receiving omeprazole 40 mg once daily had a slight advantage over those receiving omeprazole 20 mg once daily. day.
Although this study is not specifically aimed at evaluating therapy for patients who have failed PPIs, it does provide us with clues to the benefit of doubling the PPI dose. In a study that did not attempt to specifically evaluate PPI failure patients, the authors evaluated whether omeprazole 40 mg daily provided additional benefit above 20 mg daily in patients requiring more than 4 weeks. Treatment of symptomatic reflux esophagitis.
During 4 weeks of adjunctive therapy, patients receiving omeprazole 40 mg daily showed a higher cure rate (64% vs 45%, P < 0.02) and reported a reduction in heartburn (72%) compared with 60%, P < 0.002). Another study demonstrated that complete resolution of symptoms was achieved only by 22–26% of GERD patients without remission, who required a double dose of PPIs. The second study clearly suggests that most patients who do not take PPIs once daily will continue to have symptoms when taking PPIs twice daily.
Other researchers have looked at symptom improvement over difficulty achieving clinical outcomes - complete symptom control. In fact, some have even suggested that people who have failed PPI therapy may be satisfied with sufficient control of heartburn symptoms, allowing patients to experience several episodes of heartburn per week.
Doubling the PPI dose also seems to be beneficial in patients with functional heartburn, who are likely to produce more PPI insufficiency. Watson et al performed a double-blind, crossover, placebo-controlled trial of omeprazole 20 mg twice daily for 4 weeks to treat patients with functional heartburn. The drug improved symptoms in 61% of subjects. As expected, almost all respondents had a positive correlation between their symptoms and cases of acid reflux. This study, although without long-term follow-up, reinforces the view that the esophageal hypersensitivity subtype in the functional heartburn group is likely to respond to higher doses of PPIs. It has not been elucidated yet to what extent one can increase the dose of PPIs and still improve symptoms or increase the number of complete responders.

Given that most GERD patients who continue to be treated with a twice-daily PPI have normal esophageal acid exposure, it is highly unlikely that increasing the PPI dose to three times daily or even higher will result in any significant additional benefit to the patient.
For patients with GERD still uncontrolled with a twice-daily PPI, there is little information in the literature on potential treatments. In GERD patients with symptoms such as regurgitation, sour or bitter taste in the mouth, and evidence of acid-free reflux or DGER while taking a twice-daily PPI, the addition of an esophageal sphincter under transient (TLESR) was found to be useful.
In one study, the addition of baclofen (20 mg three times daily), a TLESR-inhibiting γ-aminobutyric (GABA)-B receptor agonist, to PPIs once daily significantly reduced PPIs. DGER exposure and DGER-related symptoms when compared to baseline. While later research supports the use of baclofen in clinical practice, anecdotal experience with the drug in patients with PPI failure has not been helpful.
In addition, baclofen can cause many side effects, such as confusion, dizziness, lightheadedness, drowsiness, weakness, and tremors. Tegaserod, a partial 5HT 4 agonist has been shown to have some limited effect on TLESR. It has yet to be determined in a placebo-controlled trial if adding tegaserod to once-daily PPI-failed patients is an effective treatment strategy. Unfortunately, there are currently no other TLESR reducers available and are therefore limited to the agents mentioned above. The role of adding a booster in patients with once-a-day PPI failure is unknown. However, in PPI-failed patients, who present with delayed gastric emptying, adding a stimulant drug is an attractive option. However, it remains unclear if the addition of a booster to those without evidence of delayed gastric emptying is a beneficial treatment.

Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs), have been shown to be highly effective in patients with noncardiac chest pain of esophageal origin. These visceral pain relievers are used in low doses that do not alter mood, to relieve esophageal pain. Currently, there are no studies proving their value in PPI-failed patients, but they may provide an alternative treatment until new and specific pain modifiers are available. gastrointestinal tract. Adding a tricyclic antidepressant to a PPI, or giving a tricyclic antidepressant only to those who do not have any improvement in PPIs are different treatment strategies that can be used in PPI failure patients.
The role of adding a bile acid binder, such as cholestyramine in PPI failure patients, has not been elucidated. It is still controversial if these treatment modalities should even be considered in GERD.

The use of antireflux surgery in patients who have not been successful with PPI therapy has not been widely recommended. For patients who fail PPIs because of symptoms suggestive of reflux into the esophageal lumen, such as regurgitation, and a sour/bitter taste in the mouth, surgery may be an effective approach.
However, studies to support such therapeutic intervention are still lacking. Similarly, the use of one of these endoscopic techniques to treat GERD in patients with PPI failure has been suggested. Several studies have reported that these endoscopic techniques can reduce or eliminate PPI use in patients who have only partially responded to PPI therapy. Despite this, the role of endoscopic therapy in GERD has been closely monitored in the last few years, showing that the complications and complications of the procedure are not significant and there is ample evidence to improve the parameters of the procedure. clinical number. Further studies are needed to evaluate the role of endoscopic interventional therapy in GERD in general and specifically in PPI failure patients in particular.

In summary, GERD patients who do not take PPIs once daily would benefit from doubling the PPI dose. If the patient continues to be symptomatic with twice-daily PPIs, diagnostic evaluation with the MII+ pH sensor and Bilitech 2000 or further treatment can be made. Both diagnostic techniques are unavailable, invasive, expensive, and somewhat laborious. Therefore, in patients with regurgitation and/or a sour/bitter taste in the mouth, baclofen, tegaserod, and anti-reflux surgery may improve symptoms. In those with clear evidence of delayed gastric emptying, an additional medication may be considered. The remaining patients should be evaluated for possible addition of modifiers with tricyclic antidepressants or serotonin reuptake inhibitors.
Most people with GERD will not notice serious complications, especially if treated. However, potentially serious complications can sometimes occur in people with severe GERD. Vinmec International General Hospital is a prestigious address trusted by many patients in performing diagnostic and treatment techniques for reflux esophagitis, refractory reflux esophagitis, gastritis .. Along with that, at Vinmec Hospital, the diagnosis through colonoscopy with the Olympus CV 190 endoscope, with the function (Narrow Banding Imaging - endoscopy with narrow light frequency band) gives imaging results. The analysis of mucosal pathology is clearer than that of conventional endoscopy, detecting ulcerative lesions, reflux in the esophagus, stomach, Barrett's modified lesions, and early cancerous lesions. .... Vinmec Hospital with modern facilities and equipment and a team of experienced experts who are always dedicated in medical examination and treatment, customers can rest assured with the online endoscopy service. colon at Vinmec International General Hospital.

References
F. Fass , M. Shapiro , Systematic review: proton-pump inhibitor failure in gastro-oesophageal reflux disease – where next? Alimentary Pharmacology and Theurapeutics, Volume22, Issue2, July 2005 Vaezi MF. ‘Refractory GERD’: acid, nonacid, or not GERD? Am J Gastroenterol 2004; 99: 989– 90. Richter JE, Bochenek W. Oral pantoprazole for erosive esophagitis: a placebo-controlled randomized clinical trial. Pantoprazole US GERD Study Group. Am J Gastroenterol 2000; 95: 3071– 80.