How do I manage an actively bleeding peptic ulcer, including resuscitation, endoscopic hemostasis, and Helicobacter pylori eradication?

Management of Peptic Ulcer with GI Bleeding

Initiate immediate resuscitation, perform urgent endoscopy with hemostatic therapy for high-risk stigmata, administer high-dose intravenous PPI (80mg bolus followed by 8mg/hour infusion for 72 hours), test and eradicate H. pylori, and discontinue all NSAIDs/aspirin. 1, 2, 3

Immediate Resuscitation and Risk Stratification

• Assess hemodynamic status first and begin aggressive fluid resuscitation with crystalloids, blood products as needed, targeting hemodynamic stability before endoscopy 3, 2
• Risk-stratify based on hematemesis, melena, hemodynamic instability (hypotension, tachycardia), severe abdominal pain, age >60 years, and comorbidities—these high-risk features mandate urgent endoscopy within 24 hours 2, 3
• Mortality for bleeding peptic ulcers is 8.6% even with optimal management, rising to 23.5% if perforation occurs, underscoring the need for aggressive early intervention 2

Pre-Endoscopic Pharmacotherapy

• Administer intravenous erythromycin (250mg IV 30-60 minutes before endoscopy) to improve gastric emptying and visualization, reducing the need for repeat endoscopy 1, 2
• Start high-dose PPI immediately (80mg IV bolus) even before endoscopy, though this does not replace the need for urgent endoscopy and does not improve mortality or rebleeding rates 4, 5, 3
• Pre-endoscopic PPI reduces the proportion of patients with high-risk stigmata at endoscopy but should never delay the procedure 5, 6

Endoscopic Management

• Perform urgent endoscopy within 24 hours for diagnosis, risk stratification using Forrest classification, and therapeutic intervention 3, 7
• Apply endoscopic hemostasis for Forrest 1a (active arterial spurting), 1b (active oozing), and 2a (non-bleeding visible vessel) using combination therapy: injection (epinephrine) plus thermal coagulation (bipolar electrocoagulation or heater probe) or mechanical clips 3, 7
• For Forrest 2b lesions (adherent clot), consider removing the clot and treating the underlying vessel if high-risk features are present, though PPI alone may suffice in lower-risk patients 7
• Forrest 2c (flat pigmented spot) and 3 (clean base) ulcers do not require endoscopic therapy 3, 7
• Obtain gastric biopsies during endoscopy for H. pylori testing (histology and/or culture), though recognize that false-negative rates are 25-55% during acute bleeding 1, 5

Post-Endoscopic PPI Therapy

• After successful endoscopic hemostasis of high-risk ulcers, continue the 80mg bolus with 8mg/hour continuous IV infusion for 72 hours to reduce early rebleeding risk 1, 2, 5
• Transition to oral PPI 40mg twice daily for days 4-14 (completing 14 days of high-dose therapy), which reduces rebleeding by 63% compared to once-daily dosing 1, 5
• After 14 days, reduce to 40mg once daily and continue for a total of 6-8 weeks to allow complete mucosal healing 1, 5
• This intensive PPI regimen is not needed for low-risk ulcers (Forrest 2c or 3); these patients can receive standard once-daily oral PPI 3

H. pylori Testing and Eradication

Initial Testing

• Test all patients for H. pylori using endoscopic biopsy during the acute episode, but recognize the high false-negative rate (25-55%) during active bleeding 4, 1, 5
• If initial testing is negative, repeat testing 4-6 weeks after the acute episode using urea breath test (88-95% sensitivity, 95-100% specificity) or stool antigen test (94% sensitivity, 92% specificity) off PPI therapy for at least 2 weeks 1, 2
• Never use serologic antibody testing for confirmation as antibodies persist for months to years after eradication 1

Eradication Therapy

• Start triple therapy 72-96 hours after initiating IV PPI once oral intake is tolerated—do not delay beyond 96 hours 1

• In areas with low clarithromycin resistance (<15%), use standard triple therapy for 14 days:

  • PPI standard dose (e.g., omeprazole 20mg) twice daily
  • Clarithromycin 500mg twice daily
  • Amoxicillin 1000mg twice daily (or metronidazole 500mg twice daily if penicillin-allergic) 1, 2

• In areas with high clarithromycin resistance, use sequential therapy for 10 days:

  • Days 1-5: PPI twice daily + amoxicillin 1000mg twice daily
  • Days 6-10: PPI twice daily + clarithromycin 500mg twice daily + metronidazole 500mg twice daily 1, 2

• If first-line therapy fails, use levofloxacin-based triple therapy for 10 days:

  • PPI twice daily
  • Levofloxacin 500mg once daily
  • Amoxicillin 1000mg twice daily 1, 2

Confirmation of Eradication

• Confirm eradication in all bleeding ulcer patients at least 4 weeks after completing therapy using urea breath test or stool antigen test, off PPI for at least 2 weeks 4, 1
• Successful H. pylori eradication reduces rebleeding from 26-62.5% to essentially 0-2.4%, making confirmation critical 4, 1, 8

NSAID and Aspirin Management

• Immediately discontinue all NSAIDs and aspirin during the acute bleeding episode, as this heals 95% of ulcers and reduces recurrence from 40% to 9% 1, 5
• For patients requiring cardiovascular prophylaxis with aspirin, restart within 1-7 days (ideally 1-3 days) once hemostasis is achieved, combined with long-term PPI therapy 5, 3
• If NSAIDs must be resumed for valid medical reasons, use the least harmful agent (ibuprofen or a COX-2 selective inhibitor like celecoxib) combined with long-term PPI therapy 1, 5
• Test for and eradicate H. pylori in all NSAID users, as eradication reduces peptic ulcer likelihood by 50% even in those continuing NSAIDs 1

Management of Rebleeding

• If rebleeding occurs after initial endoscopic therapy (60-76% occur within 72 hours), perform a second endoscopic treatment using the same or alternative hemostatic techniques 1, 3
• If bleeding persists or recurs after a second endoscopic attempt, proceed to surgery or interventional radiology (angiographic embolization) 3
• Endoscopic band ligation can be considered as salvage therapy if standard injection and thermal methods fail 9

Follow-Up and Long-Term Management

For Gastric Ulcers

• Perform repeat endoscopy at 6 weeks post-discharge to confirm complete healing and exclude malignancy, as 2-5% of gastric ulcers harbor cancer 1, 5
• Continue PPI therapy until healing is confirmed on follow-up endoscopy 1, 5

For Duodenal Ulcers

• Endoscopic confirmation of healing is not necessary after successful H. pylori eradication unless NSAIDs must be continued 1

Long-Term PPI Therapy

• Discontinue PPI after documented H. pylori eradication in uncomplicated duodenal ulcers, as rebleeding becomes extremely rare 1, 5
• Maintain indefinite PPI therapy for:
  • Chronic NSAID users who cannot discontinue 1, 5
  • Aspirin users with cardiovascular disease 5
  • Idiopathic ulcers (H. pylori-negative, NSAID-negative) 3

Critical Pitfalls to Avoid

• Do not rely on a single negative H. pylori test during acute bleeding—false-negative rates are 25-55%, mandating repeat testing outside the acute context 1, 5
• Do not delay H. pylori eradication therapy beyond 96 hours after starting IV PPI, as this is the optimal window for initiating oral therapy 1
• Do not use PPI therapy as a substitute for urgent endoscopy in actively bleeding patients—endoscopy is essential for diagnosis and definitive hemostasis 4, 2
• Do not skip follow-up endoscopy for gastric ulcers—malignancy must be excluded in all cases 1, 5
• Do not restart NSAIDs without concurrent PPI therapy in patients with a history of bleeding ulcer 1, 5
• Do not use potassium-competitive acid blockers (P-CABs like vonoprazan) as first-line therapy—PPIs remain the standard due to superior cost-effectiveness and long-term safety data 1, 2