A 52-year-old woman with rheumatoid arthritis has been on naproxen 500 mg twice daily for 2 years. She now presents with epigastric pain, nausea, and hematemesis. Upper endoscopy reveals a 1.5 cm antral gastric ulcer with active bleeding. She denies H. pylori infection (previously tested negative). Her hemoglobin has dropped from 12.5 g/dL to 9.2 g/dL. Which of the following is the most appropriate immediate management?

Explanation

## NSAID-Induced Peptic Ulcer Disease with Acute Bleeding **Key Point:** NSAID-induced peptic ulcer disease (PUD) with active bleeding is a medical emergency requiring immediate cessation of the NSAID, aggressive acid suppression, and endoscopic hemostasis. ### Pathophysiology of NSAID-Induced Ulcers **High-Yield:** NSAIDs cause gastric ulcers through two main mechanisms: 1. **Inhibition of protective prostaglandins** — COX inhibition reduces PGE₂ and PGI₂, which normally: - Stimulate mucus and bicarbonate secretion - Maintain gastric mucosal blood flow - Promote mucosal cell proliferation and repair 2. **Direct mucosal injury** — NSAIDs are weak acids that can directly damage the gastric epithelium ### Why This Patient Is High-Risk | Risk Factor | Present in This Case | Impact | |-------------|----------------------|--------| | Age ≥ 65 years | No (52 years) | Moderate risk | | Female sex | Yes | Slightly increased risk | | Chronic NSAID use | Yes (2 years) | High risk | | H. pylori infection | No (negative) | Reduces risk slightly, but not protective | | Concurrent PPI use | Not mentioned | Risk would be lower if on PPI | | Ulcer complications (bleeding) | Yes | Indicates severe disease | **Clinical Pearl:** The absence of H. pylori does NOT protect against NSAID-induced ulcers. In fact, H. pylori-negative patients on NSAIDs have a higher risk of ulcer complications (bleeding, perforation) because the ulcer is purely NSAID-mediated. ### Immediate Management Algorithm ```mermaid flowchart TD A[NSAID-induced PUD with active bleeding]:::outcome --> B[Discontinue NSAID immediately]:::action B --> C[Resuscitate: IV fluids, blood transfusion if Hb < 8]:::action C --> D[Start high-dose PPI: omeprazole 40 mg IV BD or pantoprazole 80 mg IV bolus + infusion]:::action D --> E[Urgent upper endoscopy for hemostasis]:::action E --> F{Bleeding controlled?}:::decision F -->|Yes| G[Continue high-dose PPI for 4-8 weeks]:::action F -->|No| H[Repeat endoscopy or interventional radiology]:::urgent G --> I[Switch to standard PPI dose after acute phase]:::action I --> J[Address pain management: acetaminophen, topical NSAIDs, or selective COX-2 inhibitor if essential]:::action ``` ### Why the Correct Answer Is Best **Discontinue naproxen immediately:** - Continuing NSAIDs in the setting of active bleeding perpetuates mucosal injury and prevents ulcer healing - The ulcer will not heal while the offending agent remains in use **High-dose PPI therapy:** - Omeprazole 40 mg IV twice daily (or equivalent) is the standard for bleeding peptic ulcers - Achieves intragastric pH > 6, which promotes platelet aggregation and clot stability - Reduces re-bleeding risk from ~30% (standard dose) to ~5–10% (high-dose) **Endoscopic hemostasis:** - Active bleeding (hematemesis) requires urgent endoscopy - Allows visualization and treatment (injection, cautery, clips) of the bleeding vessel - Reduces mortality and need for surgery ### Why Other Options Are Wrong **Option A (Continue naproxen + low-dose PPI):** - Continuing the NSAID is contraindicated in active bleeding - Omeprazole 20 mg once daily is suboptimal; high-dose IV PPI is required for bleeding ulcers - This approach will lead to continued bleeding and re-ulceration **Option C (Switch to celecoxib):** - While COX-2 selective inhibitors have a lower GI toxicity profile, they are NOT appropriate in acute bleeding - The NSAID must be discontinued entirely until the ulcer heals (4–8 weeks) - Celecoxib can be considered later for chronic pain management if absolutely necessary, but only after ulcer healing is confirmed - Celecoxib still carries GI risk and should be combined with PPI if used **Option D (Sucralfate + continue naproxen):** - Sucralfate is a weak cytoprotective agent; it is not adequate for bleeding ulcers - Continuing naproxen is contraindicated - Taking NSAIDs with food does NOT prevent ulcer formation or bleeding **Mnemonic for NSAID GI Complications:** **BLEED** - **B**leeding (from ulcers) - **L**esions (gastric and duodenal ulcers) - **E**rosions (acute mucosal damage) - **E**sophageal injury (if tablets dissolve in esophagus) - **D**iarrhea (from altered gut flora and motility) ### Follow-Up Management After acute hemostasis: 1. Continue high-dose PPI for 4–8 weeks until ulcer healing is confirmed by repeat endoscopy 2. Discontinue NSAID permanently or use only if absolutely essential (with concurrent PPI and consideration of COX-2 selective inhibitor) 3. Manage pain with acetaminophen (up to 3 g/day), topical NSAIDs, or non-pharmacological measures 4. If NSAID is essential for RA management, use the lowest effective dose of a COX-2 selective inhibitor (celecoxib 100–200 mg daily) WITH a PPI (omeprazole 20 mg daily or equivalent) 5. Avoid concurrent use of other ulcerogenic drugs (corticosteroids, anticoagulants) [cite:Harrison 21e Ch 297; KD Tripathi 8e Ch 12] **Warning:** Never continue NSAIDs in a patient with NSAID-induced bleeding peptic ulcer. This is a common exam trap and a critical clinical error.