Gastroesophageal reflux disease

H. pylori Testing: NPS – StePPIng the appropriate path with GORD medicines recommends testing for H. pylori before long-term PPI therapy in specific cases, while Australian Prescriber states that H. pylori eradication does not reduce GORD symptoms and is not routinely recommended.

Gastro-oesophageal reflux disease (GORD) is a chronic condition where stomach contents reflux into the oesophagus, causing symptoms and potential complications. It is a prevalent condition, affecting 10-15% of the population in Australia, with increasing incidence attributed to lifestyle factors such as obesity.

Symptoms

GORD presents with a variety of symptoms, which can be classified into typical and atypical categories:

Typical Symptoms:

• Heartburn: A burning sensation behind the breastbone, often after meals and at night, exacerbated by lying down or bending over.
• Regurgitation: The effortless return of acidic stomach contents into the mouth, causing a sour or bitter taste.

Atypical Symptoms:

• Chest Pain: Non-cardiac chest pain that mimics angina.
• Throat Symptoms: Chronic sore throat, hoarseness, or laryngitis.
• Respiratory Symptoms: Chronic cough, asthma, or recurrent pneumonia.
• Other Symptoms: Dysphagia (difficulty swallowing), odynophagia (painful swallowing), nausea, excessive belching, and bloating.

Diagnosis

Diagnosing GORD involves evaluating symptoms and, in some cases, performing diagnostic tests.

Clinical Diagnosis:

• Symptom Evaluation: A presumptive diagnosis can be made based on the presence of typical symptoms, particularly if they improve with PPI therapy.
• Red Flags: Presence of alarm symptoms (red flags) necessitates further investigation to rule out serious conditions such as malignancy or significant complications.

Red Flags Requiring Further Investigation:

• Dysphagia (difficulty swallowing)
• Odynophagia (painful swallowing)
• Unexplained weight loss
• Persistent vomiting
• Gastrointestinal bleeding (haematemesis or melaena)
• Iron deficiency anaemia
• New onset of symptoms in individuals over 55 years

Diagnostic Tests:

• Endoscopy: – Normal findings in two-thirds of patients do not exclude GORD
  • Indicated for patients with red flags
  • Persistent symptoms despite adequate PPI trial
  • Treatment of complications (e.g., dilatation of oesophageal strictures)
  • Evaluation before and after anti-reflux surgery
  • Screening for Barrett’s oesophagus in high-risk patients (e.g., overweight men over 50)
• 24-hour pH Monitoring: Measures acid exposure in the oesophagus and is useful for patients not responding to PPI therapy or those being evaluated for surgery.
• Oesophageal Manometry:
  • Required for a minority of patients
  • Assesses oesophageal motility and is used in refractory cases or pre-surgical evaluations.
• Barium Swallow: Generally not recommended for routine diagnosis due to low sensitivity and specificity.

Helicobacter pylori Testing:

• Routine testing for H. pylori is not recommended for GORD as it does not cause the condition and may offer some protection against it.
• However, it may be considered in dyspeptic patients without red flags.
• Slightly protective against GORD, Barrett’s oesophagus, and oesophageal adenocarcinoma
• Eradication not effective in reducing GORD symptoms

Management

Management of GORD includes lifestyle modifications, pharmacological therapy, and, in some cases, surgical intervention.

Lifestyle Modifications:

• Weight Loss: Most effective intervention, with a dose-dependent relationship between weight reduction and symptom relief.
• Dietary Changes:
  • Avoid foods and beverages that trigger symptoms (e.g., high-fat meals, alcohol, coffee, chocolate, citrus fruits, tomato products, spicy foods, carbonated beverages).
  • avoidance of meals 2–3 hours before bedtime if there are nocturnal symptoms.
• Meal Timing: Avoid eating 2-3 hours before bedtime and reduce meal sizes.
• Smoking Cessation: Recommended due to its role as a risk factor for GORD.
• Bed Elevation: Raising the head of the bed can reduce nocturnal symptoms by decreasing acid reflux episodes during sleep.
• Other Changes: Avoiding vigorous exercise after meals and adopting a healthy eating pattern.

Pharmacological Management:

Proton Pump Inhibitors (PPIs):

• Trial of PPI:
  • Frequently used for diagnosis
  • Useful, cost-effective, and helpful in predicting response to therapy
  • Treatment duration: 4–8 weeks, taken 30-60 minutes before a meal
  • A negative trial does not exclude diagnosis but reduces likelihood and prompts consideration of alternatives
  • Standard dose PPI
    • esomeprazole 20 mg
    • omeprazole 20 mg
    • pantoprazole 40 mg
• Maintenance Therapy: After initial symptom control, step down to the lowest effective dose or on-demand therapy. Long-term use is generally reserved for patients with severe erosive oesophagitis, scleroderma oesophagus, or Barrett’s oesophagus.

H2 Receptor Antagonists:

• Used as an alternative or adjunct to PPIs, particularly for on-demand treatment.

Adverse Effects of PPIs:

• Headache
• diarrhoea
• interstitial nephritis
• hypomagnesaemia
• reduced vitamin B12 absorption
• increased risk of Clostridium difficile infection
• CAP – pneumonia

Persistent Symptoms:

Persistent Symptoms in GORD

• Non-response to PPI Therapy:
  • 20-30% of patients with GORD do not respond completely to PPI therapy.
  • Common conditions confused with GORD:
    • Delayed gastric emptying
    • Functional dyspepsia
    • Functional heartburn (oesophageal hypersensitivity)
  • Other reasons for suboptimal response:
    • Non-adherence (reported at 46-55% in persistent symptoms)
    • Inappropriate dosing
    • Poor understanding of PPI pharmacokinetics (70% of GPs and 20% of gastroenterologists incorrectly instruct patients on dosing)
      • Pharmacokinetic Properties:
        • Elimination half-life for all PPIs is approximately 1 hour.
        • Time to maximum plasma concentration (tmax) varies widely (1-5 hours) due to formulation and food effects.
      • Clinical Efficacy Comparisons of PPIs
        • Omeprazole 20 mg:
          • Well-studied and used as a benchmark for comparing other PPIs.
        • Lansoprazole 30 mg:
          • Slightly improved acid suppression in one study compared to omeprazole 20 mg.
          • No significant difference in another study.
          • Not superior to omeprazole 40 mg.
        • Pantoprazole 40 mg:
          • Significantly higher daytime pH on day 1 and day 7 compared to omeprazole 20 mg.
          • Similar potency to omeprazole on a mg-for-mg basis.
        • General Efficacy:
          • Omeprazole, lansoprazole, pantoprazole, and rabeprazole have similar efficacy for healing acid-related diseases.
        • Esomeprazole (S-Omeprazole)
        • Metabolic Advantage:
          • Higher plasma concentration and AUC compared to omeprazole.
          • Improved intragastric pH profile.
        • Clinical Outcomes:
          • Esomeprazole 40 mg od superior to other PPIs at standard doses for achieving higher 24-hour median intragastric pH.
          • Greater number of patients achieving intragastric pH ≥ 4.0 for at least 12 hours per day.
          • Higher rates of healing erosive GERD and sustained resolution of heartburn compared to omeprazole 20 mg, lansoprazole 30 mg, or pantoprazole 40 mg od.
        • Dosing Considerations:
          • Short half-life (60-90 minutes) limits nighttime drug presence.
          • Twice-daily dosing provides significantly greater acid suppression than once-daily dosing.
          • Esomeprazole 40 mg bd superior to pantoprazole 40 mg bd and lansoprazole 30 mg bd for maintaining intragastric pH at 4.0 or lower.

• Intensification of Acid Suppression:
  • Increasing to twice-daily PPI doses
  • Trying a different PPI due to pharmacokinetic and pharmacogenetic differences (e.g., CYP2C19 metabolism)
  • Adding a night-time H2-receptor antagonist (tachyphylaxis may develop in 2-6 weeks)
  • Limited evidence for prokinetic drugs or sucralfate in GORD treatment

Medical Management

• Non-acid or Weakly Acid Reflux: Most common cause of medically refractory GORD.
• Baclofen:
  • Reduces reflux events by inhibiting transient lower oesophageal sphincter relaxations.
  • Adverse effects such as drowsiness in up to 63% of patients.
  • Long-term data are lacking.
• Other Drugs: Currently under investigation with no significant breakthroughs.

Surgical Management

• Indications for Anti-reflux Surgery:
  • Refractory symptoms despite maximal medical management
  • Intolerance to treatment
  • Symptomatic complications unresponsive to medical therapy
• Laparoscopic Fundoplication:
  • Common and effective in well-selected patients
  • Involves constructing a cuff of gastric tissue around the lower oesophageal sphincter
  • Effective when symptoms are due to GORD, not atypical features
  • Does not significantly reduce Barrett’s oesophagus or oesophageal adenocarcinoma risk
• Gastric Bypass Surgery:
  • Roux-en-Y procedure and laparoscopic gastric banding reduce GORD symptoms due to substantial weight loss.
  • Sleeve gastrectomy often increases or precipitates reflux symptoms.

Patient Advice

• Adherence to Treatment: Emphasize the importance of taking PPIs correctly (30-60 minutes before meals) and adhering to prescribed lifestyle modifications.
• Monitoring Symptoms: Patients should monitor and report any worsening or new symptoms.
• Stepping Down Medication:
  • Gradual reduction of PPI dose or frequency, with the
  • goal of using the lowest effective dose or
  • switching to on-demand therapy.
• Diet and Lifestyle: Encourage maintaining a healthy weight, identifying and avoiding dietary triggers, and adopting healthy eating habits.
• Regular Follow-ups: Regular reviews to reassess symptoms, evaluate the need for continued medication, and adjust treatment plans as needed.

Inadequate Reflux Symptom Control

• Check Adherence: Ensure patients are taking PPI regularly and at the optimal time
• Further Investigation: If symptoms persist, consider endoscopy to exclude other conditions
• High-Dose PPI Treatment: Standard PPI dose twice daily is more effective than double dose once daily
• Referral: Refer to a specialist if symptoms do not respond to high-dose PPI treatment

Patient Action Plan

• Combining Lifestyle Changes with PPIs:
  • Use a printed Patient Action Plan to explain the importance of lifestyle changes with PPIs
  • Patients can identify goals for stepping down and stopping PPI medicines
  • View a list of lifestyle changes to help manage reflux symptoms