What medications are used to manage upper gastrointestinal bleeding (UGIB)?

Medications for Upper Gastrointestinal Bleeding

Primary Pharmacologic Therapy: Proton Pump Inhibitors

For patients with nonvariceal UGIB and high-risk stigmata who have undergone successful endoscopic therapy, administer high-dose intravenous PPI therapy: pantoprazole or omeprazole 80 mg IV bolus followed by continuous infusion at 8 mg/hour for exactly 72 hours. 1, 2

Pre-Endoscopy PPI Administration

• Start PPI therapy immediately upon presentation, even before endoscopy, with either pantoprazole or omeprazole 80 mg IV bolus 2, 3, 4
• This may downstage endoscopic lesions and reduce the need for endoscopic intervention, though it should never delay urgent endoscopy 2, 3
• Pre-endoscopy PPI administration is recommended by multiple international consensus groups despite not replacing the need for endoscopic evaluation 4, 5

Post-Endoscopy High-Dose PPI Protocol

The 72-hour continuous infusion protocol is critical for patients with high-risk endoscopic stigmata (active bleeding, visible vessel, or adherent clot) after successful endoscopic hemostasis:

• Continue 8 mg/hour continuous infusion for exactly 72 hours, as rebleeding risk is highest during the first three days 2, 4
• This regimen significantly reduces rebleeding rates (5.9% vs 10.3%, p=0.03) and mortality compared to placebo or H2-receptor antagonists 2, 4
• After 72 hours, transition to oral PPI twice daily through day 14, then once daily 1, 2, 3
• Continue total PPI therapy for 6-8 weeks to allow complete mucosal healing 4

Important caveat: High-dose PPI therapy is specifically indicated for high-risk stigmata after successful endoscopic therapy—it is not a substitute for endoscopic hemostasis and should not delay urgent endoscopy 4

Alternative Dosing Considerations

• For hemodynamically stable patients without high-risk stigmata, intermittent IV bolus dosing (pantoprazole 40 mg IV every 12 hours) may be equally effective and more cost-efficient 6, 7
• Oral PPIs may be effective in stable patients who can tolerate oral therapy, though further evaluation is needed for higher-risk stigmata 7

Adjunctive Pharmacologic Therapies

Prokinetic Agents

• Administer erythromycin 250 mg IV 30-60 minutes before endoscopy to enhance gastric visualization by promoting gastric emptying 3, 8
• This is particularly useful when blood or clots obscure endoscopic visualization 3

Vasoactive Drugs (for Variceal Bleeding)

If variceal bleeding is suspected, initiate vasoactive drug therapy immediately:

• Terlipressin: 2 mg IV every 4 hours for first 48 hours, then 1 mg every 4 hours thereafter 2
• Somatostatin: 250 μg/hour continuous infusion with initial 250 μg bolus 2
• Octreotide: 50 μg/hour continuous infusion with initial 50 μg bolus 2
• Continue vasoactive drugs for 3-5 days in confirmed variceal bleeding 2

Antibiotic Prophylaxis (for Cirrhotic Patients)

• Administer ceftriaxone or norfloxacin in patients with cirrhosis and suspected variceal bleeding 2
• Continue antibiotics for 3-5 days in confirmed variceal bleeding 2
• Antibiotic prophylaxis reduces bacterial infections and mortality in cirrhotic patients with UGIB 2

Secondary Prophylaxis and Long-Term Management

Helicobacter pylori Eradication

• Test all patients with bleeding peptic ulcers for H. pylori and provide eradication therapy if positive 2, 3
• Eradication significantly reduces ulcer recurrence and rebleeding rates 1, 2
• Testing during acute bleeding may have increased false-negative rates; confirmatory testing outside the acute context may be necessary 2

PPI Therapy for Patients Requiring Antithrombotic Agents

• For patients with previous ulcer bleeding who require antiplatelet or anticoagulant therapy, continue PPI therapy indefinitely 1, 3
• For patients requiring NSAIDs, use a PPI with a cyclooxygenase-2 inhibitor to reduce rebleeding 1, 3
• Restart aspirin within 3-7 days when cardiovascular risks outweigh gastrointestinal risks 1, 3, 4
• Aspirin plus PPI therapy is preferred over clopidogrel alone to reduce rebleeding 1, 3

Critical Pitfalls to Avoid

• Never use epinephrine injection alone for endoscopic hemostasis—always combine with thermal coagulation or mechanical therapy 1, 3
• Do not rely solely on PPI therapy without endoscopic intervention in active bleeding 3
• Do not discontinue PPI therapy before 6-8 weeks, as this may not allow adequate time for mucosal healing 4
• Do not delay restarting antiplatelet therapy in patients requiring cardiovascular prophylaxis beyond 7 days 3
• Pantoprazole has less interaction concern with clopidogrel compared to omeprazole and esomeprazole, which inhibit CYP2C19 and reduce clopidogrel's active metabolite 2

Resuscitation and Blood Products

• Transfuse red blood cells when hemoglobin is <80 g/L in patients without cardiovascular disease; use a higher threshold for those with cardiovascular disease 1, 2, 3
• Use crystalloids (not colloids) for initial fluid resuscitation to restore end-organ perfusion 2
• The majority of patients require 1-2 liters of saline; if shock persists, plasma expanders are needed as ≥20% of blood volume has been lost 2