Peptic Ulcer Disease
Management of Peptic Ulcer Disease (PUD) and Ulcer Bleeding
1.0 Introduction and Scope
1.1 Purpose and Definition of PUD
The strategic management of Peptic Ulcer Disease (PUD) is critical to ensuring optimal patient outcomes and efficient resource utilization. This protocol establishes a standardized, evidence-based framework for the diagnosis, risk stratification, and treatment of PUD. Adherence to this protocol is intended to reduce recurrence rates, minimize complications, and promote consistent care across all clinical settings.
Peptic Ulcer Disease is defined as a discrete break in the gastric or duodenal mucosa that penetrates through the muscularis mucosae. This is a crucial distinction from gastritis or gastropathy, which represent more superficial mucosal irritation or microscopic injury without a definitive, penetrating defect. PUD arises when mucosal defense mechanisms are overwhelmed by aggressive factors such as luminal acid and pepsin.
The primary etiologies of PUD include:
- Helicobacter pylori infection: The most common cause worldwide, leading to chronic gastritis that alters gastrin and acid physiology.
- Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and aspirin: These agents cause both topical epithelial injury and systemic inhibition of prostaglandins, which are essential for mucosal defense (e.g., mucus production, bicarbonate secretion, and mucosal blood flow).
- Acid hypersecretory states: Conditions such as Zollinger-Ellison syndrome (gastrinoma) lead to marked increases in gastric acid production.
- Stress-related mucosal disease: Typically seen in critically ill patients (e.g., with burns, trauma, or sepsis) due to mucosal ischemia from systemic hypoperfusion.
Accurate initial diagnosis and risk stratification are fundamental to tailoring an effective management plan and preventing serious complications.
2.0 Initial Diagnosis and Risk Stratification
2.1 Clinical Presentation
Recognizing the varied clinical presentations of PUD is critical for timely diagnosis and intervention. While epigastric pain—often described as a "burning" or "gnawing" sensation—is the hallmark symptom, its relationship to meals can suggest the ulcer's location. It is crucial to note that PUD may be clinically silent until a complication occurs, particularly in elderly patients and chronic NSAID users.
| Duodenal Ulcer | Gastric Ulcer
| Pain is classically relieved by meals. | Pain is classically worsened by meals, which can lead to a fear of eating, early satiety, and subsequent weight loss.
| Pain often returns 2-3 hours after eating. | More common in older patient populations.
| Nocturnal pain is common. |
| More common in younger patient populations. |
2.2 Alarm Features Mandating Urgent Endoscopy
The presence of "alarm features" signals potential complications and mandates urgent endoscopic evaluation to establish a definitive diagnosis and rule out serious underlying pathology. It is critical to identify these features upon initial patient assessment.
- Bleeding: The presence of hematemesis (vomiting blood), melena (black, tarry stools), or "coffee-ground" emesis. A brisk upper gastrointestinal bleed may also present with hematochezia.
- Anemia: Unexplained iron deficiency anemia may be the only sign of chronic, occult blood loss from an ulcer.
- Weight Loss: Unintentional and significant weight loss is a concerning feature that may suggest an underlying malignancy.
- Vomiting: Persistent vomiting can indicate gastric outlet obstruction due to ulcer-related scarring or edema.
- Early Satiety or Dysphagia: A feeling of fullness after eating very little or difficulty swallowing may also point toward obstruction or malignancy.
The identification of one or more of these alarm features necessitates a prompt referral for definitive endoscopic evaluation.
3.0 Endoscopic Evaluation and Ulcer Classification
3.1 Endoscopy Protocol and Biopsy Strategy
Endoscopy is the gold standard for the diagnosis of PUD. It provides direct visualization of the mucosa, allowing for definitive diagnosis, tissue sampling to determine etiology and exclude malignancy, and therapeutic intervention in cases of bleeding. The biopsy strategy is determined by the ulcer's location.
- Gastric Ulcers: All gastric ulcers require biopsy to definitively exclude malignancy. The standard protocol is to obtain samples from at least four quadrants of the ulcer edge.
- Duodenal Ulcers: Duodenal ulcers are rarely malignant and do not require routine biopsy unless they present with atypical features or fail to heal with appropriate therapy.
3.2 Ulcer Classification by Appearance
The endoscopic appearance of an ulcer provides crucial information regarding its potential for malignancy. Clinicians must be able to differentiate benign and malignant characteristics to guide biopsy and follow-up strategies.
| Benign Appearance | Malignant Appearance
| Smooth, round, or oval shape | Irregular, "heaped-up," or rolled margins
| "Punched-out" crater | Necrotic base
| Radiating mucosal folds that reach the ulcer edge | Eccentric or interrupted mucosal folds
These visual cues, combined with histological analysis, determine the subsequent management pathway.
4.0 Management of Helicobacter pylori-Associated PUD
4.1 Diagnostic Testing for H. pylori
Accurate diagnosis and complete eradication of Helicobacter pylori are the most critical steps in managing H. pylori-associated PUD and preventing ulcer recurrence.
- Urea Breath Test (UBT) & Stool Antigen Test: These noninvasive tests are preferred for initial diagnosis and for confirmation of eradication (test-of-cure) due to their high sensitivity and specificity.
- Biopsy Urease Test (CLO test) & Histology: These invasive tests are performed during endoscopy. The biopsy urease test provides a rapid presumptive diagnosis, while histology allows for direct visualization of the organism and concurrent assessment of gastritis.
Protocol Directive: To avoid false-negative results, patients must discontinue Proton Pump Inhibitors (PPIs) for at least 2 weeks and bismuth-containing compounds or antibiotics for at least 4 weeks prior to testing.
4.2 Eradication Regimens
Selection of an eradication regimen must be based on current guidelines, local antibiotic resistance patterns, and patient history of macrolide exposure.
- Preferred Regimen (Bismuth Quadruple Therapy):
- Components: PPI (twice daily), Bismuth subsalicylate (four times daily), Tetracycline (four times daily), and Metronidazole (three times daily).
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- Duration: 14 days.
- Alternative Regimen (Concomitant Therapy):
- Components: PPI (twice daily), Clarithromycin, Amoxicillin, and Metronidazole.
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- Duration: 10-14 days.
Protocol Directive: Avoid clarithromycin triple therapy unless local resistance to clarithromycin is known to be <15% and the patient has no prior macrolide exposure.
4.3 Confirmation of Eradication (Test-of-Cure)
A test-of-cure is required in all patients treated for H. pylori to confirm successful eradication. This step is essential to minimize the risk of ulcer recurrence. The test (urea breath test or stool antigen) must be performed at least 4 weeks after the completion of antibiotic therapy and at least 2 weeks after stopping PPIs.
5.0 Protocol for Acute Peptic Ulcer Bleeding
5.1 Initial Resuscitation and Medical Management
Immediate and aggressive resuscitation is the first priority in managing acute ulcer bleeding and must precede endoscopic intervention. The primary goal is to restore hemodynamic stability.
- Hemodynamic Support: Establish two large-bore intravenous (IV) lines. Administer crystalloid fluids to restore volume. Type and crossmatch blood for potential transfusion.
- Transfusion Criteria: Transfuse packed red blood cells (PRBCs) to maintain a Hemoglobin level >7 g/dL.
- Coagulopathy Correction: Administer platelets if the count is <50,000/μL in the setting of active bleeding. Correct any underlying coagulopathy as clinically indicated.
- Assess Laboratory Markers: Assess for an elevated BUN/Creatinine ratio (>30:1), a strong indicator of an upper gastrointestinal bleed.
- Proton Pump Inhibitor (PPI) Therapy: Administer a high-dose IV PPI regimen. The standard dose is an 80 mg IV bolus followed by an 8 mg/hr continuous infusion. (Note: High-dose intermittent IV PPI, e.g., 40mg IV q12h, may be considered a non-inferior alternative in certain clinical settings).
- GI Consultation: Request an urgent gastroenterology consultation for endoscopy to be performed within 24 hours, or sooner if the patient remains hemodynamically unstable despite resuscitation.
5.2 Endoscopic Risk Stratification: Forrest Classification
The Forrest classification is a critical tool used during endoscopy to stratify the risk of rebleeding based on the ulcer's appearance. This classification directly guides the need for endoscopic therapy.
| Forrest Class | Description | Rebleeding Risk
| Ia | Spurting Hemorrhage | ~90%
| Ib | Oozing Hemorrhage | ~50%
| IIa | Non-bleeding visible vessel | ~40-50%
| IIb | Adherent clot | ~25%
| IIc | Flat pigmented spot | ~10%
| III | Clean ulcer base | ~5%
5.3 Endoscopic Hemostasis Therapy
Endoscopic therapy is required for all ulcers with high-risk stigmata: Forrest Ia, Ib, IIa, and IIb.
This protocol mandates the use of dual therapy, which has been shown to be superior to monotherapy in preventing rebleeding. This consists of an epinephrine injection to achieve temporary vasoconstriction, combined with a second, more durable modality such as thermal coagulation (heater probe) or mechanical therapy (hemoclips). This approach is mandated as epinephrine alone has a high rate of rebleeding.
Endoscopic therapy is not indicated for ulcers with low-risk stigmata (Forrest IIc, III), as the risk of rebleeding is low and does not justify the procedural risk.
5.4 Post-Endoscopy Management
Post-procedure care is stratified based on the endoscopic findings and intervention performed.
- High-Risk Stigmata (Post-Therapy): Continue the continuous IV PPI infusion (8 mg/hr) for 72 hours following successful endoscopic hemostasis to prevent rebleeding.
- Low-Risk Stigmata (IIc, III): Transition the patient to an oral PPI, advance their diet as tolerated, and plan for early hospital discharge.
5.5 Management of Rebleeding: Escalation of Care Algorithm
For patients who rebleed after initial successful endoscopic hemostasis, a clear escalation algorithm must be followed.
- First Rebleed: Attempt a second endoscopic evaluation with dual hemostasis therapy. The success rate of second-look hemostasis is approximately 75%.
- Second Rebleed (Failure of second EGD): If bleeding persists or recurs after a second endoscopic attempt, the next step is Interventional Radiology for angiographic embolization.
- Failure of IR: If angiographic embolization is unavailable or unsuccessful, the final step is surgical consultation for definitive hemostasis, such as vessel ligation or oversewing of the ulcer.
Clinical Pearl: Massive hemorrhage from a posterior duodenal ulcer often involves erosion into the gastroduodenal artery. Similarly, bleeding gastric ulcers on the lesser curvature may involve the left gastric artery. Recognition of these high-risk locations should increase vigilance.
Practice Point: Routine, scheduled "second-look" endoscopy is not recommended. Endoscopy should only be repeated if there is clear clinical evidence of rebleeding.
Adherence to this escalation algorithm is critical for minimizing mortality in refractory ulcer bleeding.
6.0 Long-Term Management and Follow-Up
6.1 PPI Duration and Surveillance Endoscopy
Appropriate follow-up, including determination of PPI therapy duration and the need for surveillance endoscopy, is key to ensuring complete ulcer healing, preventing recurrence, and detecting malignancy. The post-treatment protocol is based on the ulcer's location and size.
| Ulcer Type | Ulcer Size | Oral PPI Duration | Surveillance Endoscopy
| Duodenal | < 2 cm | 4 weeks | Not required if asymptomatic.
| Duodenal | ≥ 2 cm (Giant) | 8-12 weeks | Consider if symptoms persist or to exclude Zollinger-Ellison syndrome (ZES).
| Gastric | Any size | 8 weeks (12 weeks if giant) | Repeat EGD at 6-8 weeks to document complete healing. If healing is incomplete, re-biopsy is required to definitively exclude malignancy.
6.2 Indications for Indefinite (Maintenance) PPI Therapy
While most patients can discontinue PPIs after ulcer healing and removal of underlying risk factors, a specific subset requires long-term, indefinite maintenance therapy to prevent recurrence. Indications for indefinite daily PPI therapy include:
- Ongoing requirement for NSAID or aspirin therapy that cannot be discontinued.
- Patient on dual antiplatelet or anticoagulation therapy with a history of an ulcer bleed.
- Idiopathic ulcers, where no cause (H. pylori or NSAID use) can be identified.
- History of recurrent or complicated ulcers despite control of primary risk factors.
- Patients with severe comorbidities where the risk of a recurrent ulcer bleed would be unacceptable.
6.3 Management of NSAID-Induced Ulcers
The management of NSAID-induced ulcers requires a focused strategy to mitigate the ongoing chemical injury to the gastric mucosa.
- Primary Goal: The first and most effective step is to stop the offending NSAID if clinically feasible.
- If NSAID Must Continue: If the patient requires ongoing NSAID therapy for a significant comorbidity, they must be maintained on indefinite daily PPI co-therapy. In this scenario, switching from a nonselective NSAID to a COX-2 inhibitor plus a PPI may offer the safest profile.
The overarching goal of long-term management is to meticulously identify and mitigate ongoing risk factors to prevent ulcer recurrence and its associated complications.
