What is the most likely cause and appropriate evaluation and management for recurrent epigastric pain with intermittent hypotension, particularly in a patient using non‑steroidal anti‑inflammatory drugs or aspirin and at risk for Helicobacter pylori infection?

Recurrent Epigastric Pain with Intermittent Hypotension: NSAID-Induced Peptic Ulcer with Bleeding Until Proven Otherwise

In a patient with recurrent epigastric pain and intermittent hypotension, especially with NSAID or aspirin use, the most likely diagnosis is peptic ulcer disease with intermittent bleeding causing hypovolemia, and this patient requires immediate hospitalization, urgent upper endoscopy within 24 hours, high-dose IV PPI therapy, permanent NSAID discontinuation, and H. pylori testing with eradication if positive. 1

Immediate Diagnostic and Management Priorities

Recognize the Life-Threatening Nature

• The combination of epigastric pain with hypotension strongly suggests active or recent upper GI bleeding with hemodynamic compromise 1
• Intermittent hypotension indicates recurrent bleeding episodes with volume depletion, which carries significant mortality risk (10,000 deaths annually in the US from peptic ulcer disease) 2
• Hospitalize immediately for resuscitation and monitoring 1

Urgent Endoscopy Protocol

• Perform upper endoscopy within 24 hours to identify the bleeding source and provide endoscopic hemostasis 1, 3
• Endoscopic therapy (thermal coagulation, clips, or injection therapy) should be applied to high-risk lesions (Forrest 1a, 2a, 2b) 1
• Pre-endoscopic erythromycin may be considered to increase diagnostic yield 3

Immediate Pharmacologic Intervention

• Start high-dose IV PPI therapy immediately without waiting for endoscopy: 80 mg esomeprazole or pantoprazole bolus, followed by 8 mg/hour continuous infusion for 72 hours 1
• This regimen significantly reduces rebleeding (5.9% vs 10.3%, p=0.03) and need for repeat endoscopic treatment 1
• Continue high-dose IV PPI infusion for a full 72 hours after successful endoscopic hemostasis 1

Critical Risk Factor Assessment

NSAID/Aspirin Exposure

• Permanently discontinue all NSAIDs immediately 1, 4
• NSAIDs and aspirin account for approximately 36% of peptic ulcer disease cases 2
• Even low-dose aspirin (75 mg daily) doubles upper GI bleeding risk 5
• Discontinuing NSAIDs heals 95% of ulcers and reduces recurrence from 40% to 9% 2

H. pylori Status

• Test all patients with peptic ulcers for H. pylori infection using urea breath test, stool antigen test, or biopsy during endoscopy 5, 4
• H. pylori infection affects approximately 42% of patients with peptic ulcer disease 2
• H. pylori infection increases NSAID-related complications 2-4 fold 5, 4
• The combination of H. pylori and NSAIDs creates synergistic risk 6

History of Prior Ulcer Disease

• A history of peptic ulcer is the single strongest risk factor, with 50-100% recurrence rate within one year if H. pylori-related 5
• Patients with prior ulcer bleeding have extraordinarily high risk of 12-36% per year for new ulcer complications 5
• Previous ulcer complications (bleeding, perforation, obstruction) dramatically increase recurrence risk 5

Post-Endoscopy Management Algorithm

Transition to Oral Therapy

• After 72 hours of IV PPI, transition to oral PPI: omeprazole 40 mg twice daily or equivalent 1
• Continue oral PPI for 6-8 weeks to ensure complete ulcer healing 1

H. pylori Eradication Protocol

• If H. pylori positive, initiate eradication therapy with triple therapy regimen (PPI + amoxicillin + clarithromycin) for 14 days 4
• Always confirm eradication success because of the risk of ulcer recurrence and bleeding in H. pylori-infected patients 7
• H. pylori eradication reduces ulcer risk from 26% to 7% when starting NSAIDs 5
• Eradication decreases peptic ulcer recurrence rates from 50-60% to 0-2% 2

Long-Term Prevention Strategy

If NSAIDs Must Be Resumed (Strongly Discouraged)

• Very high-risk patients should avoid NSAIDs entirely 6
• If absolutely necessary, use COX-2 selective inhibitor (celecoxib) combined with PPI 4
• The combination of COX-2 inhibitor and PPI provides superior protection compared to either agent alone 4
• However, even with omeprazole plus diclofenac, recurrent bleeding rates remain 12.8% per year in high-risk patients 5

If Aspirin Required for Cardiovascular Disease

• Patients with established cardiovascular disease who require aspirin should start PPI and generally re-institute aspirin soon after bleeding ceases (within 7 days, ideally 1-3 days) 3
• Low-dose aspirin (75-81 mg) plus PPI reduces ulcer risk to near-baseline levels 5
• H. pylori eradication plus PPI co-therapy is mandatory in patients with prior ulcer bleeding who require aspirin 5

PPI Duration

• Discontinue PPI after 6-8 weeks if NSAIDs are permanently stopped and ulcer is healed 1
• Continue PPI indefinitely only if ongoing NSAID use (which should be avoided) 1
• For idiopathic ulcers, long-term anti-ulcer therapy is required 3

Critical Pitfalls to Avoid

Common Management Errors

• Never assume PPI therapy alone is sufficient protection in patients with prior H. pylori ulcers or ongoing NSAID use 5
• H2-receptor antagonists are inadequate for NSAID-associated gastric ulcers; they only protect against duodenal ulcers 4
• Poor compliance with gastroprotective agents increases the risk of NSAID-induced adverse events 4-6 fold 6, 4
• H. pylori eradication alone is not sufficient in patients with previous ulcer history who need NSAIDs—additional PPI therapy must be considered 6

High-Risk Scenarios Requiring Extra Vigilance

• Combination therapy with multiple antiplatelet agents (aspirin plus clopidogrel) substantially increases bleeding risk 5
• Anticoagulants (warfarin) substantially increase bleeding risk 5
• Corticosteroids have synergistic risk with NSAIDs 5
• Older age is a major risk factor for NSAID-related complications 5, 4

When Current Strategies Fail

• In patients with prior ulcer bleeding, neither celecoxib alone (9.8% recurrence) nor omeprazole plus diclofenac (12.8% recurrence) was sufficiently protective 5
• If recurrent bleeding occurs after endoscopic therapy, perform second endoscopic treatment 3
• If bleeding persists or recurs after second endoscopy, proceed to surgery or interventional radiology 3