What is the best treatment for a patient with a bleeding peptic ulcer, possibly related to NSAID use or Helicobacter pylori infection?

Treatment of Bleeding Peptic Ulcer

For bleeding peptic ulcer, immediately initiate high-dose intravenous PPI therapy with an 80 mg bolus followed by 8 mg/hour continuous infusion for 72 hours after endoscopic hemostasis, then transition to oral PPI 40 mg twice daily for 11 days, followed by once-daily dosing for 6-8 weeks total. 1, 2

Immediate Resuscitation and Endoscopic Management

• Stabilize hemodynamics first with intravenous fluid resuscitation and blood product transfusion as needed before proceeding to endoscopy 2
• Perform urgent endoscopy for both diagnosis and therapeutic hemostasis—PPIs do not replace endoscopy in active bleeding 3, 2
• Administer pre-endoscopy erythromycin (250 mg IV) to improve gastric visualization and reduce the need for repeat endoscopy 1, 2
• Apply endoscopic hemostasis techniques (epinephrine injection, thermal coagulation, or hemoclips) for high-risk stigmata including active arterial bleeding (Forrest 1a), visible vessels (Forrest 2a), and adherent clots (Forrest 2b) 1, 2

High-Dose PPI Protocol

The evidence strongly supports the following specific regimen:

• Administer 80 mg PPI bolus immediately after successful endoscopic hemostasis 1, 2, 4
• Follow with 8 mg/hour continuous intravenous infusion for 72 hours 1, 2, 4
• After 72 hours, switch to oral PPI 40 mg twice daily for 11 days (days 4-14) 2
• Then continue once-daily PPI dosing for the remainder of 6-8 weeks total 1, 2

Important nuance: While one 2014 meta-analysis suggested intermittent PPI dosing may be non-inferior 5, and another 2014 trial found no difference between high and low-dose pantoprazole 6, the most recent 2025-2026 guidelines and the 2020 WSES consensus continue to recommend high-dose continuous infusion based on the landmark studies showing significant reductions in rebleeding (5.9% vs 10.3%), need for surgery, and mortality 1, 2. In clinical practice, follow the guideline-recommended high-dose protocol for the highest-risk patients.

Helicobacter pylori Testing and Eradication

• Test all patients with bleeding peptic ulcer for H. pylori infection before discharge using urea breath test or stool antigen test (preferred over serology) 1, 2, 7
• Critical caveat: Tests have increased false-negative rates during acute bleeding episodes, so repeat testing 4-8 weeks after the bleeding episode if initial results are negative 1, 7
• Start H. pylori eradication treatment when oral feeding is reintroduced, typically after 72-96 hours of IV PPI therapy 1, 7

Standard triple therapy for 14 days (in areas with low clarithromycin resistance <15%): 1, 7

• PPI standard dose (omeprazole 20 mg, lansoprazole 30 mg, or pantoprazole 40 mg) twice daily
• Clarithromycin 500 mg twice daily
• Amoxicillin 1000 mg twice daily (or metronidazole 500 mg twice daily if penicillin allergy)

• Confirm H. pylori eradication at least 4 weeks after completing therapy using urea breath test or stool antigen test 2, 7
• Failure to eradicate H. pylori leads to 40-50% recurrence rates over 10 years 3, 7

NSAID Management

• Immediately discontinue all NSAIDs and aspirin when bleeding peptic ulcer is diagnosed 2, 7
• Discontinuing NSAIDs heals 95% of ulcers and reduces recurrence from 40% to 9% 3, 7
• If NSAIDs must be continued for valid medical reasons, switch to selective COX-2 inhibitor (celecoxib) combined with long-term PPI therapy 7
• For patients requiring aspirin for cardiovascular protection, restart within 1-7 days once bleeding is controlled, as cardiovascular risk typically outweighs bleeding risk 2

Duration of PPI Therapy

The duration depends on the underlying etiology: 1, 2

• Uncomplicated duodenal ulcer with successful H. pylori eradication: 6-8 weeks total, then discontinue 1
• Gastric ulcer or complicated duodenal ulcer: Continue PPI until complete healing is confirmed and H. pylori eradication is documented 1
• Ongoing NSAID use: Maintain long-term PPI therapy for secondary prophylaxis 1, 2, 7
• Recurrent ulcers despite H. pylori eradication: Consider long-term PPI therapy 7

Hospitalization and Monitoring

• Hospitalize patients who undergo endoscopic hemostasis for high-risk stigmata for at least 72 hours, as 60-76% of rebleeding episodes occur within this timeframe 3, 2
• If rebleeding occurs despite optimal medical and endoscopic therapy, seek surgical consultation or consider percutaneous angiographic embolization where available 2

Critical Pitfalls to Avoid

• Never skip H. pylori testing—this accounts for the majority of treatment failures and recurrences 3, 7
• Do not use PPIs as a substitute for urgent endoscopy in patients with signs of active bleeding (hematemesis, melena, hemodynamic instability) 3, 2
• Do not perform routine second-look endoscopy after successful initial hemostasis—it is not recommended and does not improve outcomes 2
• Be aware of PPI drug interactions—PPIs may reduce absorption of medications requiring acidic environments (ketoconazole, iron, certain antiretrovirals) and may interact with antiplatelet medications 3, 8
• Avoid long-term PPI use without indication—potential risks include fractures, chronic kidney disease, C. difficile infection, and micronutrient deficiencies 8