What is the recommended management of peptic ulcer disease?

Management of Peptic Ulcer Disease

All patients with peptic ulcer disease should be tested for Helicobacter pylori and receive eradication therapy if positive, combined with proton pump inhibitor (PPI) therapy, while immediately discontinuing NSAIDs when present. 1, 2

Initial Assessment and Risk Stratification

Urgent endoscopy is mandatory for patients presenting with hematemesis, melena, hemodynamic instability, severe abdominal pain suggesting perforation, or persistent vomiting, as these high-risk presentations carry mortality rates of 8.6% for bleeding ulcers and 23.5% for perforated ulcers. 2

For stable patients without alarm features and age <60 years, proceed with the test-and-treat strategy rather than immediate endoscopy. 2

Acute Management of Bleeding Peptic Ulcers

High-Dose PPI Protocol

For bleeding ulcers with high-risk stigmata after endoscopic hemostasis:

• Administer 80 mg IV PPI bolus followed by 8 mg/hour continuous infusion for 72 hours 3, 2
• After 72 hours, transition to pantoprazole 40 mg twice daily for 11 days (days 4-14), which reduces rebleeding risk by 63% compared to once-daily dosing 2
• Then continue pantoprazole 40 mg once daily for total duration of 6-8 weeks 2

Most patients should be hospitalized for at least 72 hours, as 60-76% of rebleeding episodes occur within this timeframe. 2

Helicobacter pylori Testing

Diagnostic Methods

Test all patients with peptic ulcer disease for H. pylori before discharge using: 3, 2

• Urea breath test (UBT): sensitivity 88-95%, specificity 95-100% 3, 2
• Stool antigen test: sensitivity 94%, specificity 92% 3, 2
• Endoscopic biopsy if endoscopy is performed 3

Critical caveat: Tests have increased false-negative rates during acute bleeding episodes, so repeat testing outside the acute context if initial results are negative. 2

H. pylori Eradication Therapy

Timing of Treatment

Start eradication therapy 72-96 hours after initiating IV PPI, once oral feeding is reintroduced—do NOT delay until discharge, as this significantly reduces compliance and increases loss to follow-up. 1, 2

First-Line Therapy (Low Clarithromycin Resistance <15-20%)

Standard triple therapy for 14 days: 3, 1

• PPI standard dose twice daily
• Clarithromycin 500 mg twice daily
• Amoxicillin 1000 mg twice daily (or metronidazole 500 mg twice daily if penicillin-allergic)

This achieves eradication rates of 77-90% in low-resistance areas. 1

Alternative First-Line (High Clarithromycin Resistance >20%)

Bismuth-based quadruple therapy for 14 days is recommended when clarithromycin resistance exceeds 20%. 1

Sequential therapy for 10 days (if compliance can be ensured): 3, 2

• Days 1-5: PPI twice daily + amoxicillin 1000 mg twice daily
• Days 6-10: PPI twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily

Second-Line Therapy (First-Line Failure)

10-day levofloxacin-amoxicillin triple therapy: 3, 1

• PPI standard dose twice daily
• Levofloxacin 500 mg once daily (or 250 mg twice daily)
• Amoxicillin 1000 mg twice daily

Switch to this regimen without waiting for culture results when standard triple therapy fails. 1

Third-Line Therapy

Culture and antibiotic susceptibility testing should guide third-line therapy selection, with treatment tailored based on identified resistance patterns. 1

Confirmation of Eradication

Test for H. pylori eradication at least 4 weeks after completing therapy and at least 2 weeks after stopping PPI using urea breath test or stool antigen test. 1

Eradication confirmation is mandatory for gastric ulcers. 1 Successful eradication reduces ulcer recurrence from 50-60% to 0-2%, while failure to eradicate leads to recurrence rates of 40-50% over 10 years. 2

NSAID-Associated Ulcers

Discontinue all NSAIDs and aspirin immediately when peptic ulcer is diagnosed, as this heals 95% of ulcers and reduces recurrence from 40% to 9%. 2

Test for and eradicate H. pylori if present, as eradication in NSAID users reduces peptic ulcer likelihood by 50%. 2

If NSAIDs must be continued for valid medical reasons: 2

• Switch to selective COX-2 inhibitor (celecoxib) with lower gastric toxicity
• Maintain long-term PPI therapy for secondary prophylaxis

For patients requiring aspirin for cardiovascular protection, combining PPI with aspirin reduces GI bleeding risk while maintaining cardiovascular benefits. 2

Duration of PPI Therapy After Eradication

For uncomplicated duodenal ulcers: Prolonged PPI therapy after H. pylori eradication is NOT recommended, as healing rate exceeds 90% without additional acid suppression. 1 Endoscopic confirmation of healing is generally unnecessary unless the patient must continue NSAID therapy. 2

For gastric ulcers and complicated duodenal ulcers: Continue PPI therapy after eradication treatment until complete healing is confirmed, as gastric ulcers require longer acid inhibition than duodenal ulcers. 1

Surgical Management

Perforated peptic ulcers are the leading indication for emergency surgery and account for approximately 40% of all ulcer-related deaths. 2 Successful surgical care requires prompt recognition, aggressive fluid resuscitation, appropriate antibiotic therapy, and timely operative intervention. 2

Common Pitfalls to Avoid

• Never delay H. pylori treatment in bleeding ulcers until after discharge, as this significantly reduces treatment compliance 1
• Do not use prolonged PPI therapy for uncomplicated duodenal ulcers after successful eradication, as this is unnecessary and increases costs 1
• PPIs should not replace urgent endoscopy in patients with active bleeding 2
• Avoid potassium-competitive acid blockers (P-CABs) like vonoprazan as first-line therapy due to higher costs, limited availability, and less robust long-term safety data compared to PPIs 2
• PPIs may reduce absorption of medications requiring an acidic environment 2