Management of Peptic Ulcer Disease with Complications
All patients with bleeding or perforated peptic ulcers must undergo H. pylori testing and receive eradication therapy if positive, combined with high-dose PPI therapy and immediate discontinuation of NSAIDs/aspirin to prevent recurrence and reduce mortality. 1
Immediate Management of Complicated Peptic Ulcer Disease
For Bleeding Peptic Ulcers
Initiate high-dose intravenous PPI therapy immediately: administer an 80 mg bolus of omeprazole (or equivalent PPI) followed by continuous infusion at 8 mg/hour for 72 hours after endoscopic hemostasis in high-risk ulcers. 2 This regimen should begin as soon as possible after diagnosis, ideally after successful endoscopic therapy. 1
Transition to oral therapy: After completing the 72-hour infusion, switch to oral PPI 40 mg twice daily for the next 11 days (completing 14 days total of high-dose therapy), then reduce to 40 mg once daily and continue for a total duration of 6-8 weeks to allow complete mucosal healing. 2, 3
Discontinue all NSAIDs and aspirin immediately when peptic ulcer bleeding is diagnosed, as this heals 95% of ulcers and reduces recurrence from 40% to 9%. 4 For patients requiring cardiovascular prophylaxis with aspirin, restart within 1-7 days (ideally 1-3 days) once hemostasis is achieved, along with continued PPI therapy. 2
For Perforated Peptic Ulcers
Obtain CT scan imaging as the primary diagnostic modality for suspected perforated peptic ulcer, as it provides superior diagnostic accuracy compared to plain radiography. 1 If CT is not promptly available, perform chest/abdominal X-ray as initial routine assessment. 1
Proceed to surgical intervention for confirmed perforation, with laparoscopic approach preferred when feasible. 1 The timing should be as soon as the patient is adequately resuscitated and stabilized. 1
Initiate empirical antibiotic therapy immediately upon diagnosis of perforation to cover polymicrobial contamination. 1
H. pylori Testing and Eradication Strategy
Testing Approach
Test all patients with bleeding or perforated peptic ulcers for H. pylori infection. 1 However, recognize that tests have increased false-negative rates during acute bleeding episodes due to the bleeding itself and high-dose PPI therapy. 2
Use non-invasive testing methods: Urea breath test (sensitivity 88-95%, specificity 95-100%) or stool antigen testing (sensitivity 94%, specificity 92%) are preferred. 1 In bleeding ulcers, endoscopic tissue biopsy may also be available. 1
Repeat testing outside the acute context if initial results are negative during the bleeding episode, as false negatives are common. 2 A confirmatory test should be performed to definitively rule out infection. 2
Eradication Regimens
For first-line therapy in areas with low clarithromycin resistance (<15%): Use standard triple therapy for 14 days consisting of PPI standard dose twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1000 mg twice daily (or metronidazole 500 mg twice daily if penicillin allergic). 1, 3 Start this regimen after 72-96 hours of intravenous PPI administration. 1
For areas with high clarithromycin resistance: Use 10-day sequential therapy with days 1-5 consisting of PPI standard dose twice daily and amoxicillin 1000 mg twice daily, followed by days 6-10 with PPI standard dose twice daily, clarithromycin 500 mg twice daily, and metronidazole 500 mg twice daily. 1, 3 This regimen requires strict compliance to be effective. 1
For second-line therapy if first-line fails: Use 10-day levofloxacin-amoxicillin triple therapy consisting of PPI standard dose twice daily, levofloxacin 500 mg once daily (or 250 mg twice daily), and amoxicillin 1000 mg twice daily. 1, 3
Document eradication after treatment completion using urea breath test or stool antigen test (not serology), as eradication reduces ulcer recurrence from 50-60% to 0-2%. 4 This confirmation is crucial to ensure successful therapy. 3
Long-Term Management and Prevention
For H. pylori-Positive Patients
Discontinue PPI after documented H. pylori eradication in uncomplicated cases, as rebleeding becomes extremely rare once the infection is cleared. 2 Eradication therapy is the definitive treatment to avoid recurrent bleeding. 1
For NSAID-Associated Ulcers
If NSAIDs must be continued for valid medical reasons: Switch to a selective COX-2 inhibitor (celecoxib) or lower-risk nsNSAID (ibuprofen) combined with long-term PPI therapy. 3, 4 Eradicating H. pylori in NSAID users reduces peptic ulcer likelihood by 50%. 3
Maintain indefinite PPI therapy for patients requiring continuous NSAID therapy or aspirin for cardiovascular disease. 2 This represents secondary prophylaxis against recurrence. 3
Follow-Up Requirements
Perform follow-up endoscopy at 6 weeks after hospital discharge for gastric ulcers (not duodenal ulcers) to confirm healing and exclude malignancy, as gastric ulcers carry risk of underlying malignancy. 2 This is mandatory for all gastric ulcers. 2
Continue PPI therapy until complete healing is confirmed on follow-up endoscopy. 2
Critical Pitfalls to Avoid
Do not rely on a single negative H. pylori test during acute bleeding, as false-negative rates are substantially elevated in this context. 2 Always confirm with repeat testing outside the acute phase. 2
Do not use empirical H. pylori eradication therapy without confirming infection, as this leads to unnecessary antibiotic exposure and does not address the true prevalence of the bacteria in your patient population. 1 Testing first is more appropriate than empirical therapy. 1
Do not continue NSAIDs without gastroprotection in patients with history of peptic ulcer disease, as the combination of H. pylori infection and NSAID use synergistically increases bleeding risk more than sixfold. 5
Do not use 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, 3