Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management

This guideline covers investigating and managing gastro-oesophageal reflux disease (GORD) and dyspepsia in people aged 18 and over. It aims to improve the treatment of GORD and dyspepsia by making detailed recommendations on Helicobacter pylori eradication, and specifying when to consider laparoscopic fundoplication and referral to specialist services.

# Introduction
Dyspepsia describes a range of symptoms arising from the upper gastrointestinal (GI) tract, but it has no universally accepted definition. The British Society of Gastroenterology (BSG) defines dyspepsia as a group of symptoms that alert doctors to consider disease of the upper GI tract, and states that dyspepsia itself is not a diagnosis. These symptoms, which typically are present for 4 weeks or more, include upper abdominal pain or discomfort, heartburn, gastric reflux, nausea or vomiting. In this guideline, gastro-oesophageal reflux disease (GORD) refers to endoscopically determined oesophagitis or endoscopy-negative reflux disease.
Some of the costs associated with treating dyspepsia are decreasing, but the overall use of treatments is increasing. As a result, the management of dyspepsia continues to have potentially significant costs to the NHS.
The use of endoscopy has increased considerably over the past decade, as awareness of its value in investigating dyspepsia and GORD has grown.
The review of 'Dyspepsia: management of dyspepsia in adults in primary care' (NICE guideline CG17) highlighted some concerns about the drug regimens that were recommended in the guideline for Helicobacter pylori (hereafter referred to as H pylori) eradication, because some bacterial resistance has developed. Overall, the review process concluded that some guidance in this area should be updated and expanded to cover aspects of specialist hospital care.
NICE guideline CG17 covered the management of several underlying causes of dyspepsia in primary care, but there is a lack of comprehensive national guidance about managing GORD (in particular, surgical management) when pharmacological treatments fail. Because of this, and the possible role of GORD (with the subsequent development of Barrett's oesophagus) as a risk factor for cancer, the scope of the guideline update was extended to cover managing GORD in secondary care.
This guideline update covers adults (18 years and older) with symptoms of dyspepsia, symptoms suggestive of GORD, or both. It also covers endoscopic surveillance for adults with a diagnosis of Barrett's oesophagus, but it does not cover the management of Barrett's oesophagus. It is important to note that children and young people (younger than 18 years) and people with a diagnosis of oesophagogastric cancer are not covered in this guideline update.
In this guideline, specialist care is defined as treatment decisions made by a consultant-led service in secondary or tertiary care.

# Drug recommendations
The guideline will assume that prescribers will use a drug's summary of product characteristics to inform decisions made with individual patients.
This guideline recommends some drugs for indications for which they do not have a UK marketing authorisation at the date of publication, if there is good evidence to support that use. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. The patient (or those with authority to give consent on their behalf) should provide informed consent, which should be documented. See the General Medical Council's Good practice in prescribing and managing medicines and devices for further information. Where recommendations have been made for the use of drugs outside their licensed indications ('off-label use'), these drugs are marked with a footnote in the recommendations.
Specific dosage information on proton pump inhibitors (PPIs) is detailed in appendix A.# Recommendations
The following guidance is based on the best available evidence. The full guideline gives details of the methods and the evidence used to develop the guidance.
These recommendations apply to adults (aged 18 and over) with symptoms of dyspepsia, symptoms suggestive of gastro-oesophageal reflux disease (GORD), or both.
People have the right to be involved in discussions and make informed decisions about their care, as described in your care.
Making decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations, and has information about prescribing medicines (including off-label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding.

# Terms used in this guideline
In this guideline, GORD refers to endoscopically determined oesophagitis or endoscopy-negative reflux disease.

# The community pharmacist
Community pharmacists should offer initial and ongoing help for people with symptoms of dyspepsia. This includes advice about lifestyle changes, using over-the-counter medication, help with prescribed drugs and advice about when to consult a GP. 
Community pharmacists should record adverse reactions to treatment and may participate in primary care medication review clinics. 

# Common elements of care
Offer simple lifestyle advice, including advice on healthy eating, weight reduction and smoking cessation. 
Advise people to avoid known precipitants they associate with their dyspepsia where possible. These include smoking, alcohol, coffee, chocolate, fatty foods and being overweight. Raising the head of the bed and having a main meal well before going to bed may help some people. 
Provide people with access to educational materials to support the care they receive. 
Recognise that psychological therapies, such as cognitive behavioural therapy and psychotherapy, may reduce dyspeptic symptoms in the short term in individual people. 
Encourage people who need long-term management of dyspepsia symptoms to reduce their use of prescribed medication stepwise: by using the effective lowest dose, by trying 'as-needed' use when appropriate, and by returning to self-treatment with antacid and/or alginate therapy (unless there is an underlying condition or comedication that needs continuing treatment). 

# Referral guidance for endoscopy
For people presenting with dyspepsia together with significant acute gastrointestinal bleeding, refer them immediately (on the same day) to a specialist.  (Also see the NICE guideline on acute upper gastrointestinal bleeding.)
Review medications for possible causes of dyspepsia (for example, calcium antagonists, nitrates, theophyllines, bisphosphonates, corticosteroids and non-steroidal anti-inflammatory drugs ). In people needing referral, suspend NSAID use. 
Think about the possibility of cardiac or biliary disease as part of the differential diagnosis. 
If people have had a previous endoscopy and do not have any new alarm signs, consider continuing management according to previous endoscopic findings. 
For more information about when to refer people to specialists when they present with symptoms that could be caused by cancer, see the NICE guideline on suspected cancer: recognition and referral.

# Interventions for uninvestigated dyspepsia
Be aware that dyspepsia in unselected people in primary care is defined broadly to include people with recurrent epigastric pain, heartburn or acid regurgitation, with or without bloating, nausea or vomiting. Also see common elements of care. 
Leave a 2week washout period after proton pump inhibitor (PPI) use before testing for Helicobacter pylori (hereafter referred to as H pylori) with a breath test or a stool antigen test. 
Offer empirical full-dose PPI therapy (see table 1 in appendix A) for 4 weeks to people with dyspepsia. 
Offer H pylori 'test and treat' to people with dyspepsia. 
If symptoms return after initial care strategies, step down PPI therapy to the lowest dose needed to control symptoms. Discuss using the treatment on an 'as-needed' basis with people to manage their own symptoms. 
Offer H2 receptor antagonist (H2RA) therapy if there is an inadequate response to a PPI. 

# Reviewing patient care
Offer people who need long-term management of dyspepsia symptoms an annual review of their condition, and encourage them to try stepping down or stopping treatment (unless there is an underlying condition or comedication that needs continuing treatment). 
Advise people that it may be appropriate for them to return to selftreatment with antacid and/or alginate therapy (either prescribed or purchased over-the-counter and taken as needed). 

# Interventions for GORD
Manage uninvestigated 'reflux-like' symptoms as uninvestigated dyspepsia. 
Offer people with GORD a full-dose PPI (see table 1 in appendix A) for 4 or 8 weeks. 
If symptoms recur after initial treatment, offer a PPI at the lowest dose possible to control symptoms. 
Discuss with people how they can manage their own symptoms by using the treatment when they need it. 
Offer H2RA therapy if there is an inadequate response to a PPI. 
People who have had dilatation of an oesophageal stricture should remain on long-term full-dose PPI therapy (see table 1 in appendix A). 
Offer people a full-dose PPI (see table 2 in appendix A) for 8 weeks to heal severe oesophagitis, taking into account the person's preference and clinical circumstances (for example, underlying health conditions and possible interactions with other drugs). 
If initial treatment for healing severe oesophagitis fails, consider a high dose of the initial PPI, switching to another full-dose PPI (see table 2) or switching to another high-dose PPI (see table 2 in appendix A), taking into account the person's preference and clinical circumstances (for example, tolerability of the initial PPI, underlying health conditions and possible interactions with other drugs). 
Offer a full-dose PPI (see table 2 in appendix A) long-term as maintenance treatment for people with severe oesophagitis, taking into account the person's preference and clinical circumstances (for example, tolerability of the PPI, underlying health conditions and possible interactions with other drugs), and the acquisition cost of the PPI. 
If the person's severe oesophagitis fails to respond to maintenance treatment, carry out a clinical review. Consider switching to another PPI at full dose or high dose (see table 2 in appendix A), taking into account the person's preference and clinical circumstances, and/or seeking specialist advice. 
Do not routinely offer endoscopy to diagnose Barrett's oesophagus, but consider it if the person has GORD. Discuss the person's preferences and their individual risk factors (for example, long duration of symptoms, increased frequency of symptoms, previous oesophagitis, previous hiatus hernia, oesophageal stricture or oesophageal ulcers, or male gender). 

# Interventions for peptic ulcer disease
Offer H pylori eradication therapy to people who have tested positive for H pylori and who have peptic ulcer disease. Also see H pylori testing and eradication. 
For people using NSAIDs with diagnosed peptic ulcer, stop the use of NSAIDs where possible. Offer full-dose PPI (see table 1 in appendix A) or H2RA therapy for 8 weeks and, if H pylori is present, subsequently offer eradication therapy. 
Offer people with gastric ulcer and H pylori repeat endoscopy 6 to 8 weeks after beginning treatment, depending on the size of the lesion. 
Offer people with peptic ulcer (gastric or duodenal) and H pylori retesting for H pylori 6 to 8 weeks after beginning treatment, depending on the size of the lesion. 
Offer full-dose PPI (see table 1 in appendix A) or H2RA therapy for 4 to 8 weeks to people who have tested negative for H pylori who are not taking NSAIDs. 
For people continuing to take NSAIDs after a peptic ulcer has healed, discuss the potential harm from NSAID treatment. Review the need for NSAID use regularly (at least every 6 months) and offer a trial of use on a limited, 'as-needed' basis. Consider reducing the dose, substituting an NSAID with paracetamol, or using an alternative analgesic or low-dose ibuprofen (1.2 g daily). 
In people at high risk (previous ulceration) and for whom NSAID continuation is necessary, consider a COX-2 selective NSAID instead of a standard NSAID. In either case, prescribe with a PPI. 
In people with an unhealed ulcer, exclude non-adherence, malignancy, failure to detect H pylori, inadvertent NSAID use, other ulcerinducing medication and rare causes such as ZollingerEllison syndrome or Crohn's disease. 
If symptoms recur after initial treatment, offer a PPI to be taken at the lowest dose possible to control symptoms. Discuss using the treatment on an 'as-needed' basis with people to manage their own symptoms. 
Offer H2RA therapy if there is an inadequate response to a PPI. 

# Interventions for functional dyspepsia
Manage endoscopically determined functional dyspepsia using initial treatment for H pylori if present, followed by symptomatic management and periodic monitoring. 
Offer eradication therapy to people testing positive for H pylori. 
Do not routinely offer re-testing after eradication, although the information it provides may be valued by individual people. 
If H pylori has been excluded and symptoms persist, offer either a low-dose PPI (see table 1 in appendix A) or an H2RA for 4 weeks. 
If symptoms continue or recur after initial treatment, offer a PPI or H2RA to be taken at the lowest dose possible to control symptoms. 
Discuss using PPI treatment on an 'as-needed' basis with people to manage their own symptoms. 
Avoid long-term, frequent dose, continuous antacid therapy (it only relieves symptoms in the short term rather than preventing them). 

# Helicobacter pylori testing and eradication

## Testing
Test for H pylori using a carbon13 urea breath test or a stool antigen test, or laboratory-based serology where its performance has been locally validated. 
Perform re-testing for H pylori using a carbon13 urea breath test. (There is currently insufficient evidence to recommend the stool antigen test as a test of eradication.) 
Do not use office-based serological tests for H pylori because of their inadequate performance. 

## Eradication
Offer people who test positive for H pylori a 7day, twice-daily course of treatment with:
a PPI (see table 3 in appendix A) and
amoxicillin and
either clarithromycin or metronidazole.Choose the treatment regimen with the lowest acquisition cost, and take into account previous exposure to clarithromycin or metronidazole. 
Offer people who are allergic to penicillin a 7day, twice-daily course of treatment with:
a PPI (see table 3 in appendix A) and
clarithromycin and
metronidazole. 
Offer people who are allergic to penicillin and who have had previous exposure to clarithromycin a 7-day course of treatment with:
a PPI (see table 3 in appendix A) and
bismuth and
metronidazole and
tetracycline. 
Discuss treatment adherence with the person and emphasise its importance. For more information about supporting adherence, see the NICE guideline on medicines adherence. 
Offer people who still have symptoms after first-line eradication treatment a 7day, twice-daily course of treatment with:
a PPI (see table 3 in appendix A) and
amoxicillin and
either clarithromycin or metronidazole (whichever was not used first-line). 
Offer people who have had previous exposure to clarithromycin and metronidazole a 7day course of treatment with:
a PPI (see table 3 in appendix A) and
amoxicillin and
tetracycline (or, if a tetracycline cannot be used, levofloxacin). 
Offer people who are allergic to penicillin (and who have not had previous exposure to a fluoroquinolone antibiotic) a 7day, twice-daily course of treatment with:
a PPI (see table 3 in appendix A) and
metronidazole and
levofloxacin. 
Offer people who are allergic to penicillin and who have had previous exposure to a fluoroquinolone antibiotic a 7-day course of:
a PPI (see table 3 in appendix A) and
bismuth and
metronidazole and
tetracycline. 
Seek advice from a gastroenterologist if eradication of H pylori is not successful with second-line treatment. 

# Laparoscopic fundoplication
Consider laparoscopic fundoplication for people who have:
a confirmed diagnosis of acid reflux and adequate symptom control with acid suppression therapy, but who do not wish to continue with this therapy long term
a confirmed diagnosis of acid reflux and symptoms that are responding to a PPI, but who cannot tolerate acid suppression therapy. 

# Referral to a specialist service
Consider referral to a specialist service for people:
-f any age with gastro-oesophageal symptoms that are nonresponsive to treatment or unexplained
with suspected GORD who are thinking about surgery
with H pylori that has not responded to second-line eradication therapy. 

# Surveillance for people with Barrett's oesophagus
Consider surveillance to check progression to cancer for people who have a diagnosis of Barrett's oesophagus (confirmed by endoscopy and histopathology), taking into account:
the presence of dysplasia (also see the NICE guideline on Barrett's oesophagus: ablative therapy)
the person's individual preference
the person's risk factors (for example, male gender, older age and the length of the Barrett's oesophagus segment).Emphasise that the harms of endoscopic surveillance may outweigh the benefits in people who are at low risk of progression to cancer (for example, people with stable non-dysplastic Barrett's oesophagus). 
  For more information about alarm signs please see the NICE guideline on suspected cancer: recognition and referral.
  This refers to evidence reviewed in 2004.
  For the assessment of allergy to beta-lactam antibiotics and referral to specialist care, see the NICE guideline on drug allergy.
  See MHRA advice for restrictions and precautions for using fluoroquinolone antibiotics due to very rare reports of disabling and potentially long-lasting or irreversible side effects affecting musculoskeletal and nervous systems. Warnings include: stopping treatment at first signs of a serious adverse reaction (such as tendonitis), prescribing with special caution in people over 60 years and avoiding coadministration with a corticosteroid (March 2019).
  In the NICE guideline on suspected cancer: recognition and referral, 'unexplained' is defined as 'a symptom(s) and/or sign(s) that has not led to a diagnosis being made by the primary care professional after initial assessment of the history, examination and primary care investigations (if any)'.# Research recommendations
The Guideline Development Group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future.

# Patient characteristics, risk factors and predictors that indicate endoscopy for excluding Barrett's oesophagus
In people who experience symptoms of gastro-oesophageal reflux disease (GORD) or symptoms suggestive of GORD, what patient characteristics, risk factors and predictors indicate when endoscopy is needed to exclude Barrett's oesophagus?

## Why this is important
The aim is to identify adults with symptoms of GORD or symptoms suggestive of GORD who may benefit from having an endoscopy for the purpose of early identification of Barrett's oesophagus (or to exclude Barrett's oesophagus).

# Laparoscopic fundoplication compared with medical management
What is the effectiveness of laparoscopic fundoplication compared with medical management in people with GORD that does not respond to optimal proton pump inhibitor (PPI) treatment?

## Why this is important
Current evidence on the clinical and cost effectiveness of laparoscopic fundoplication compared with medical management involves people who had relatively good treatment control with PPIs at baseline. The driver was the desire to be free from medication rather than their GORD being non-responsive to PPIs.

# Effective proton pump inhibitor dosage for severe erosive reflux disease
What is the clinical effectiveness of double-dose PPIs in people with severe erosive reflux disease (Los Angeles classification grade C/D or SavaryMiller grade 3/4):
to reduce severe oesophagitis
to control symptoms
as maintenance therapy?

## Why this is important
People with severe erosive reflux disease or severe oesophagitis (Los Angeles classification grade C/D or SavaryMiller grade 3/4) experience severe heartburn, and prolonged acid and pepsin exposure in the lower oesophagus, which can affect their day-to-day wellbeing. It would substantially improve people's quality of life if an optimal treatment regimen could be identified. Currently, there is a lack of evidence on the efficacy of 'double-dose' PPIs in treating severe erosive reflux disease.

# Other specialist management
What specialist management is effective for people whose symptoms do not respond to PPIs despite optimum primary care, or for people whose symptoms return after surgery?

## Why this is important
There is a small group of people whose symptoms do not resolve, despite medical management and/or surgery for reflux. The group should be divided into people with proven (by pH monitoring) GORD and people with symptoms but no diagnosed reflux. The first group should have a trial of a twice-daily, high-dose PPI versus a standard or full-dose PPI. The second group should have a trial of tricyclic antidepressants versus standard or full-dose PPI. The purpose of any treatment should focus on improving quality of life.

# Specialist investigation
What specialist investigations should be conducted to exclude a diagnosis of functional dyspepsia in people with uninvestigated dyspepsia that does not respond to PPIs or H2 receptor antagonists (H2RAs) despite optimum primary care?

## Why this is important
People with uninvestigated dyspepsia that fails to respond to PPIs or H2RAs, despite optimum primary care, can have a poor quality of life. It is important to ensure that appropriate investigations are carried out to make the correct diagnosis or to correct misdiagnosis, so that the most appropriate treatment can be offered.# Finding more information and resources
You can see everything NICE says on gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management in our interactive flowchart on dyspepsia and gastro-oesophageal reflux disease.
To find out what NICE has said on topics related to this guideline, see our web page on gastro-oesophageal reflux, including Barrett's oesophagus.
For full details of the evidence and the guideline committee's discussions, see the full version of the guideline. You can also find information about how the guideline was developed, including details of the committee.
NICE has produced tools and resources to help you put this guideline into practice. For general help and advice on putting NICE guidelines into practice, see resources to help you put guidance into practice.# Appendix A: Dosage information on proton pump inhibitors
In 2004, when the original guideline was developed (CG17), doses of proton pump inhibitors (PPIs) were based on the British National Formulary (BNF) at the time, as in table 1 below.
During the update of this guideline (2014), the Guideline Development Group (GDG) has further defined the PPI doses specifically for severe oesophagitis and H pylori eradication therapy, as in tables 2 and 3 below.
Table 1 PPI doses relating to evidence synthesis and recommendations in the original guideline (CG17; 2004)
Proton pump inhibitor
Full/standard dose
Low dose (on-demand dose)
Double dose
Esomeprazole
mg1 once a day
Not available
mg3 once a day
Lansoprazole
mg once a day
mg once a day
mg2 twice a day
Omeprazole
mg once a day
mg2 once a day
mg once a day
Pantoprazole
mg once a day
mg once a day
mg2 twice a day
Rabeprazole
mg once a day
mg once a day
mg2 twice a day
Lower than the licensed starting dose for esomeprazole in gastro-oesophageal reflux disease (GORD), which is 40 mg, but considered to be dose-equivalent to other PPI. When undertaking meta-analysis of dose-related effects, NICE classed esomeprazole 20 mg as a full-dose equivalent to omeprazole 20 mg.
Off-label dose for GORD.
40 mg is recommended as a double dose of esomeprazole because the 20mg dose is considered equivalent to omeprazole 20 mg.
Table 2 PPI doses for severe oesophagitis in this guideline update (2014)
Proton pump inhibitor
Full/standard dose
Low dose (ondemand dose)
High/double dose
Esomeprazole
mg1 once a day
mg1 once a day
mg1 twice a day
Lansoprazole
mg once a day
mg once a day
mg2 twice a day
Omeprazole
mg1 once a day)
mg1 once a day)
mg1 twice a day
Pantoprazole
mg once a day
mg once a day
mg2 twice a day
Rabeprazole
mg once a day
mg once a day
mg2 twice a day
Change from the 2004 dose, specifically for severe oesophagitis, agreed by the GDG during the update of CG17.
Off-label dose for gastro-oesophageal reflux disease.
Table 3 PPI doses for 
      H pylori
     eradication therapy in this guideline update (2014)
Proton pump inhibitor
Dose
Esomeprazole
mg
Lansoprazole
mg
Omeprazole
40 mg
Pantoprazole
mg
Rabeprazole
mg