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Management of Patients With Refractory Reflux-Like Symptoms Despite Proton Pump Inhibitor Therapy: Evidence-Based Consensus Statements

Armstrong D, Hungin AP, Kahrilas PJ, Sifrim D, Moayyedi P, Vaezi MF, et al.

Aliment Pharmacol Ther, 2025 Feb;61(4):636-650.
PMID: 39740235 DOI: 10.1111/apt.18420

BACKGROUND: Many patients diagnosed with gastro-oesophageal reflux disease (GERD) have persistent symptoms despite proton pump inhibitor (PPI) therapy.
AIMS: The aim of this consensus is to provide evidence-based statements to guide clinicians caring for patients with refractory reflux-like symptoms (rRLS) or refractory GERD.
METHODS: This consensus was developed by the International Working Group for the Classification of Oesophagitis. The steering committee developed specific PICO questions pertaining to the management of PPI rRLS. Methodologists conducted systematic reviews of the literature. The quality of evidence and strength of recommendations were rated using the GRADE approach.
RESULTS: Consensus was reached on 13 of 17 statements on diagnosis and management. For rRLS, suggested diagnostic strategies included endoscopy, ambulatory reflux testing and oesophageal manometry. The group did not reach consensus on the role of oesophageal biopsies or the use of reflux-symptom association in patients undergoing reflux testing. The group suggested against increasing the PPI dose in patients who had received 8 weeks of a twice-daily PPI. Adjunctive alginate or antacid therapy was suggested. There was no consensus on the role of adjunctive prokinetics. There was little role for adjunctive transient lower oesophageal sphincter relaxation (TLESR) inhibitors or bile acid sequestrants. Endoscopic or surgical anti-reflux procedures should not be performed in patients with rRLS in the absence of objectively confirmed GERD.
CONCLUSIONS: The management of rRLS should be personalised, based on shared decision-making regarding the role of diagnostic testing to confirm or rule out GERD as a basis for treatment optimisation. Anti-reflux procedures should not be performed without objective confirmation of GERD.

Matched MeSH terms: Antacids/therapeutic use
Fulltext Single dose antacid therapy before caesarian section

Tan KH

Med J Malaysia, 1984 Sep;39(3):246-9.
PMID: 6100563

The severity of pulmonary aspiration depends mainly on the acidity of the aspirate. Mist magnesium trisilicate (MMT) has been used for many years at the maternity unit in General Hospital, Kuala Lumpur, to neutralise the acidic gastric contents in all obstetric patients requiring caesarian section. This preliminary study shows that a single dose of 15 mls of MMT before general anaesthesia raises the intragastric pH to above the critical level of 2.5 in 80% of the patients. Recently there have been doubts over the protective role of MMT. Sodium citrate which is the other antacid available may be a better alternative.

Matched MeSH terms: Antacids/therapeutic use*
Helicobacter pylori infection and non-ulcer dyspepsia: the effect of treatment with colloidal bismuth subcitrate

Goh KL, Parasakthi N, Peh SC, Wong NW, Lo YL, Puthucheary SD

Scand. J. Gastroenterol., 1991 Nov;26(11):1123-31.
PMID: 1754846

A study was undertaken to determine the role of Helicobacter pylori in non-ulcer dyspepsia (NUD) and to determine the efficacy of colloidal bismuth subcitrate (CBS) in the treatment of NUD. Seventy-one patients were randomly allocated (double blind) to CBS or placebo, two tablets twice daily for 4 weeks. The severity of dyspepsia was scored and endoscopies performed before and after treatment, and antral biopsy specimens were taken for bacteriologic and histologic examination. Forty patients had H. pylori infection, and all had changes of chronic active gastritis. H. pylori was cleared from 17 to 21 patients (81%) treated with CBS, whereas none of the 19 patients treated with placebo cleared the bacteria. Improvement in histology was noted in 15 of 21 patients (71.4%) treated with CBS, whereas no improvement was noted in any of the placebo controls. Thirty-one patients were negative for H. pylori. All had either normal gastric histology or minor degrees of inflammation. Seventeen of these patients received CBS, and 14 received placebo. All groups reported improvement in the symptom score; however, the H. pylori-positive, CBS-treated group recorded a significantly higher improvement than the other groups (p less than 0.001). Relapse of H. pylori infection after initial clearance of the bacteria was high. Twelve of 16 patients evaluated relapsed 1 month after withdrawal of CBS.

Matched MeSH terms: Antacids/therapeutic use*
Fulltext Evaluation of therapies in the treatment of Helicobacter pylori associated non-ulcer dyspepsia

Nafeeza MI, Shahimi MM, Kudva MV, Ahmad H, Isa MR, Sood IM, et al.

Singapore Med J, 1992 Dec;33(6):570-4.
PMID: 1488663

This randomised double blind placebo controlled study evaluated the effectiveness of colloidal bismuth subcitrate (CBS), ampicillin and their combination in the treatment of Helicobacter Pylori in non-ulcer dyspepsia (NUD) and assessed if elimination of this organism is associated with improvement of gastritis and the symptoms. Forty-eight NUD patients with H. pylori and histologic gastritis were randomly allocated to one of the three regimens for 28 days. Symptoms were assessed before and after treatment. Forty-three patients completed the trial. Repeat endoscopy within 48 hours of completing treatment showed suppression of H. pylori in 6 of 7 patients (85.7%) on combined therapy and one of 8 patients (12.5%) on CBS therapy (p = 0.0205). There was no suppression of the bacteria in patients treated with ampicillin. Repeat endoscopy performed 2 weeks after completing treatment showed suppression of H. pylori in 3 of 7 patients (42.9%) on combined therapy and none in the other two groups. Patients on combined therapy who had suppression of H. pylori, 48 hours or 2 weeks after completing treatment were noted to have historical improvement of their gastritis (p = 0.0001 and p = 0.05 respectively). This was also associated with improvement of symptoms in these patients.

Matched MeSH terms: Antacids/therapeutic use
Fulltext Gastro-oesophageal reflux disease in 'difficult-to-control' asthma: prevalence and response to treatment with acid suppressive therapy

Wong CH, Chua CJ, Liam CK, Goh KL

Aliment Pharmacol Ther, 2006 May 1;23(9):1321-7.
PMID: 16629937 DOI: 10.1111/j.1365-2036.2006.02888.x

BACKGROUND: The causal association between gastro-oesophageal reflux disease (GERD) and difficult-to-control asthma is unclear.
AIM: To determine the prevalence of GERD and response to proton pump inhibitor therapy in patients with difficult-to-control asthma.
METHODS: Consecutive patients with difficult-to-control asthma as defined by persistent and recurrent symptoms despite on optimal asthmatic medications were recruited for the study. GERD was diagnosed by symptoms, gastroscopy and 24-h oesophageal pH monitoring. All patients were prescribed a course of lansoprazole 30 mg daily for 8 weeks. Improvement to treatment was assessed by a change in pulmonary symptom score and also by patient's subjective assessment of improvement.
RESULTS: Seventeen of 30 (56.7%) patients with difficult-to-control asthma were diagnosed with GERD. Pulmonary symptom score improved significantly only in patients with GERD (35.0 to 21.0; P = 0.002). Twelve of 16 (75%) patients with GERD reported an improvement in asthma symptoms; 1 of 11 (9.1%) without GERD reported mild symptom improvement. There was no significant change in peak expiratory flow rate and forced expiratory volume.
CONCLUSIONS: More than half of patients with difficult-to-control asthma were diagnosed with GERD. In these patients the severity of asthma improved significantly with potent acid suppression therapy. This underlines the critical role of acid reflux in this subset of patients with difficult-to-control asthma.
Study site: Respiratory clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

Matched MeSH terms: Antacids/therapeutic use*
Fulltext Randomised clinical trial: the effectiveness of Gaviscon Advance vs non-alginate antacid in suppression of acid pocket and post-prandial reflux in obese individuals after late-night supper

Deraman MA, Abdul Hafidz MI, Lawenko RM, Ma ZF, Wong MS, Coyle C, et al.

Aliment Pharmacol Ther, 2020 06;51(11):1014-1021.
PMID: 32343001 DOI: 10.1111/apt.15746

BACKGROUND: Late-night supper increases the risk of postprandial reflux from the acid pocket especially in obesity. An alginate-based, raft-forming medication may be useful for obese patients with GERD.
AIMS: To compare the efficacy of Gaviscon Advance (Reckitt Benckiser, UK) and a non-alginate antacid in post-supper suppression of the acid pocket and post-prandial reflux among obese participants.
METHODS: Participants underwent 48 h wireless and probe-based pH-metry recording of the acid pocket and lower oesophagus, respectively, and were randomised to single post-supper (10 pm) dose of either Gaviscon Advance or a non-alginate antacid on the second night. Primary outcomes were suppression of median pH of acid pocket and lower oesophagus, measured every 10-minutes post-supper for 1 h. Secondary outcomes were suppression of % time pH

Matched MeSH terms: Antacids/therapeutic use*