Case study: Managing PPI-resistant GORD

Combined behaviourial therapy and medication are essential, write Dr Neel Sharma, Professor Lawrence Ho Khek Yu and Dr Jamie Dalrymple

Gastroscopy can assess the severity of oesophagitis and exclude other pathology (Photo: SPL)
Gastroscopy can assess the severity of oesophagitis and exclude other pathology (Photo: SPL)

Case study: Heartburn

A 44-year-old man presents with continuing symptoms of heartburn, despite four months of double-dose lansoprazole. He mentions his symptoms are present most days of the week. He has experienced no haematemesis or melena. He does not smoke or consume alcohol. He admits to often ‘eating on the go’ owing to the busy nature of his job.

PPI-resistant gastro-oesophageal reflux disease (GORD) is seen in up to 40% of patients with GORD.1 It is defined as the persistence of symptoms, typically heartburn and/or regurgitation, in patients managed with a double dose of PPI for at least three months.1

In the first instance, GPs should reassess patients in terms of symptomatology. Heartburn is typically burning in the upper epigastrium and potentially retrosternal.

Atypical symptoms should alert a potential alternative diagnosis. For example, predominant regurgitation could imply rumination syndrome, which requires specialist input.

Lifestyle and medication

Following symptom assessment, it is important to address lifestyle factors. In this case, ‘eating on the go’ could imply poor dietary habits. However, there is conflicting evidence on whether foods that are highly spiced, fatty or acidic can exacerbate symptoms in PPI-resistant cases.

It is also unclear whether raising the head of the bed or avoidance of late meal consumption are beneficial in a refractory setting. Although not applicable in this patient’s case, smoking and alcohol intake can be problematic and steps should be taken to curb their use if relevant.

Medication should be assessed and patients should be questioned about compliance and appropriate dosing time. PPI therapy is best taken up to 30 minutes before meals.

Patients should be assessed for  underlying psychological concerns, such as anxiety or depression, which may highlight the possibility of functional heartburn. Those with irritable bowel type symptoms may also experience PPI-resistant GORD.

Further investigations

Upper GI endoscopy should be undertaken by primary care endoscopists or gastroenterology specialists. Assessment for alternative diagnoses, such as eosinophilic oesophagitis, should be sought.

Referral for manometry can also be considered to exclude dysmotility disorders, such as achalasia, where failure of relaxation of the lower oesophageal sphincter contributes to symptoms such as heartburn.

In addition, pH impedance monitoring should be explored, to assess the pattern of episodes of reflux and refractory-based symptoms.

A poor correlation can imply the underlying condition is unlikely to be reflux related, but potentially functional in nature, with evidence of visceral hypersensitivity from positive symptoms but normal oesophageal acid exposure.

Changing medications

Evidence exists for the use of alternative medications. In this patient’s case, lansoprazole can be switched to omeprazole or esomeprazole. If this fails to provide benefit, add-on medication may be warranted.

H2 receptor antagonists can be considered and taken at night, due to nocturnal gastric acid production, although it is important to note that evidence regarding their benefit is limited.2 There is also merit in the use of alginate antacid based therapies.

Analysing the primary mechanism of GORD, evidence highlights the existence of transient lower oesophageal sphincter relaxations. In this regard, trials demonstrate value for the use of GABA-B agonists, such as baclofen, which aid in inhibiting transient lower oesophageal sphincter relaxations.3

Side-effects may be a concern and should be noted. Examples include CNS-related disturbance, such as dizziness and vomiting.

Surgical intervention

If further medication fails to prove efficacious, patients should be referred for consideration of surgical intervention. Research demonstrates merit for intervention in the form of fundoplication, typically performed laparoscopically.

Endoscopic intervention is also possible, courtesy of the Stretta procedure,4 in which radiofrequency energy is delivered to the lower oesophageal sphincter. The end result is significant muscular remodelling and subsequently reduced reflux.

Patients who still have symptoms, despite no obvious biochemical or anatomical abnormality, are referred to as functional patients. This group typically shows evidence of oesophageal hypersensitivity, hypervigilance and/or psychological conditions such as depression or anxiety.

There is no quick fix for these patients and specialist input should be sought.

In view of possible oesophageal hypersensitivity and hypervigilance, pain medication should be considered, either tricyclic antidepressants such as amitriptyline or SSRIs such as citalopram.5 Associated psychological factors may benefit from CBT or relaxation intervention.

  • Dr Sharma is visiting clinical research fellow, Division of Gastroenterology and Hepatology, National University Hospital, Singapore; Professor Ho Khek Yu is senior consultant, Division of Gastroenterology & Hepatology, vice dean (research), Yong Loo Lin School of Medicine, National University of Singapore; Dr Dalrymple is chairman, Primary Care Society for Gastroenterology

1. Dellon ES, Shaheen NJ. Gastroenterology 2010; 139(1): 7-13 e3.
2. Rackoff A, Agrawal A, Hila A et al. Diseases of the Esophagus 2005; 18(6): 370-3.
3. Lidums I, Lehmann A, Checklin H et al. Gastroenterology 2000; 118(1): 7-13.
4. Arts J, Sifrim D, Rutgeerts P et al. Digestive Diseases and Sciences 2007; 52(9): 2170-7.
5. Fass R, Sifrim D. Gut 2009; 58(2): 295-309.

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