GERD in adults: what to do in case of “failure” of PPIs?

Gastroesophageal reflux disease (GERD) refers to the intermittent or permanent passage of gastric contents into the esophagus. Physiological, it is brief and essentially post-prandial. It becomes pathological when frequent and/or prolonged reflux induces symptoms and/or endoscopic lesions.

Typical signs are heartburn (upward heartburn) and acid regurgitation. These very specific symptoms make it possible to clinical diagnosis in 90% of patients. In the event of age over 50 years or atypical signs (thoracic or epigastric pain without pyrosis, ENT manifestations, chronic cough), explorations are necessary (algorithm of diagnostic approach below).

In a subject under the age of 50, with no warning signs (dysphagia, anemia, deterioration in general condition, etc.), empirical treatment can be offered without exploration, most often with proton pump inhibitors (PPIs), which inhibit acid secretion (but have no action on regurgitation). However, approximately 30 to 40% of these patients do not respond (or partially) to these molecules.

What to offer to these patients?

It must be specified during the interrogation the exact nature of the symptoms. Many are described as refractory “pyrosis” when it comes to epigastric or cervical burns without the ascending retrosternal character (the probability of GERD is much lower).

Symptoms persisting under PPI are generally of a dyspeptic or ENTwhile the typical manifestations have disappeared. The regurgitation are less relieved by PPIs than heartburn. Finally, the coexistence of functional digestive disorders is a major factor in treatment failure (patients have underlying visceral hypersensitivity).

Optimizing PPI treatment is essential. First of all: to evaluate the observance and the methods of taking because less than half of patients comply with the initial prescription. We must ensure that PPIs are taken on an empty stomach, 15 to 20 minutes before a meal (better antisecretory efficacy). Then, we can suggest divide the single dose into 2 doses daily (1/2 dose morning and evening), change PPI or increase the dosage. double it (1 dose morning and evening, off-label) relieves 20 to 25% more patients. The combination of PPIs with alginates (Gaviscon) is legal; on the other hand, the addition of prokinetics has never been shown to be effective.

What explorations?

The objective is to prove GERD and/or its persistence under PPI.

Upper digestive endoscopy is indicated in first intention: it makes it possible to document an authentic esophagitis peptic (inflammation of the esophagus with erosions and ulcerations of the inner wall, of varying severity, which may induce endobrachyesophagus or stricture) or Barrett’s esophagus (a precancerous condition in which the esophageal squamous lining changes into an intestinal-like epithelium ). It can also provide arguments in favor of a motor disorder of the esophagus (stasis, cardiac jerk).

In the absence of endoscopic peptic lesions, a 24-hour pH-metry* (to be carried out after a week of weaning) makes it possible to document GERD: it looks for a pathological esophageal acid exposure (time spent at pH < 4 greater than 5%). If this examination is normal (no acid exposure), the hypothesis of pathological GERD is ruled out. Two possibilities: if there is a temporal association between the symptoms and the recorded reflux, we speak of acid-sensitive esophagus or reflux hypersensitivity ; if the patient has ascending retrosternal burns but there is no temporal association symptoms-reflux we evoke a “functional heartburn” (picture).


*In patients in whom pathological GERD has previously been demonstrated in the absence of treatment (esophagitis or positive pH-metry), a pH-impedancemetry (carried out under treatment) is indicated to assess its persistence under PPI.

What treatment?

No “antireflux” medication is currently availablewith the exception of baclofen which reduces their number but whose tolerance is very poor. Nevertheless, given the major role of visceral hypersensitivity in the pathophysiology of reflux resistant to PPIs, we can propose in some cases pain modulators such as tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs), at lower doses than those that alter mood. Indeed, citalopram and amitriptyline have shown their efficacy in acid-sensitive esophagus (controlled studies vs placebo).

For patients with genuine refractory GERD, surgery (laparoscopic fundoplication) may be considered: it is indicated when a postural syndrome with regurgitation persists, after having ruled out a severe esophageal motility disorder by esophageal manometry.

Reminder of PPI prescription methods

To see : Macaigne G. IPP: not without danger? Rev Prat 2018;32(1011);830-1.

GERD in people over 60 and/or if typical and close symptoms (once a week or more): Half-dose PPI for 4 weeks (except full dose omeprazole) then possibly on demand in the event of episodic symptoms. If frequent and early relapses on stopping the PPI: maintenance treatment at the minimum effective dose.

Non-severe esophagitis (erythema, non-circular erosions): same as GERD.

Severe esophagitis (circular mucosal erosions, chronic ulceration, stenosis or even endobrachy-oesophagus): full-dose PPI for 8 weeks with esophagogastroduodenal fibroscopy (FOGD) of control at the stop. Systematic maintenance treatment offered over the long term at the minimum effective dose.

Daily dosages (half dose, full dose)

• Esomeprazole (Inexium, Nexium Control): 20 mg, 40 mg

• Lansoprazole (Lanzor, Ogast, Ogastoro): 15mg, 30mg

• Omeprazole (Mopral, Zoltum, Mopralpro): 10 mg, 20 mg

• Pantoprazole (Inipomp, Eupantol, Ipraalox): 20 mg, 40 mg

• Rabeprazole (Pariet): 10 mg, 20 mg

According to :

Zerbib F. Reflux difficult to treat: what to do? Reverend Prat Med Gen 2020;34(1037);185-6.

Macaigne G. IPP: not without danger? Reverend Prat Med Gen 2018;31(1011);830-1.

Cinzia Nobile, The Practitioner’s Review

To know more :

Abbes L, Zinzindohoue F. Gastroesophageal reflux disease. Reverend Prat Med Gen 2017;31(986):581-2.

Zerbib F. Suspicion of gastroesophageal reflux: diagnostic strategy. Reverend Prat Med Gen 2020;34(1037);185-6.

Zinzindohoue F. Dossier. Gastroesophageal reflux disease in adults. Rev Prat 2016;66(10):1079-95.

PPIs are not automatic! Rev Prat (online) November 12, 2020.

Leave a Comment