What is the recommended dose of a proton pump inhibitor (PPI) for bleeding?

Recommended Proton Pump Inhibitor Dosing for Upper Gastrointestinal Bleeding

For non-variceal upper GI bleeding with high-risk stigmata after successful endoscopic hemostasis, administer omeprazole or pantoprazole 80 mg IV bolus followed by 8 mg/hour continuous infusion for exactly 72 hours. 1

Initial Bolus Dosing

• Start PPI therapy immediately upon presentation, even before endoscopy is performed, with an 80 mg IV bolus of either omeprazole or pantoprazole 1, 2
• This pre-endoscopic dosing may reduce stigmata of recent bleeding and improve visualization during endoscopy 1
• Do not delay urgent endoscopy while relying solely on PPI therapy—PPIs are adjunctive to endoscopic hemostasis, not a replacement 1

Continuous Infusion Protocol

• Following the initial 80 mg bolus, immediately begin continuous IV infusion at 8 mg/hour for exactly 72 hours after successful endoscopic therapy 1, 2
• This high-dose continuous infusion regimen reduces mortality (OR 0.56,95% CI 0.34-0.94) compared to no PPI or H2-receptor antagonists 1
• The continuous infusion also significantly reduces rebleeding rates (OR 0.43,95% CI 0.29-0.63) and decreases the need for surgical intervention 1

Physiologic Rationale

• Blood clot stability requires a gastric pH above 6 for adequate platelet aggregation, while clot lysis occurs when pH drops below 6 1
• High-dose continuous infusion PPIs are more effective than H2-receptor antagonists or intermittent PPI dosing at maintaining gastric pH above 6 1
• The acidic environment (pH <5.4) also activates pepsin, which disaggregates platelet plugs and destabilizes clots 3

Post-Infusion Oral Therapy

• After completing the 72-hour IV infusion, transition to oral PPI 40 mg twice daily through day 14 1, 2
• Continue oral PPI 40 mg once daily from day 15 onward for a total of 6-8 weeks to allow complete mucosal healing 1, 2
• Discontinuing PPI therapy before 6-8 weeks is a common pitfall that prevents adequate mucosal healing 1, 2

High-Risk Stigmata Requiring This Protocol

• Active arterial bleeding (Forrest Ia) 1
• Visible vessel (Forrest IIa) 1
• Adherent clot (Forrest IIb) 1
• The mortality and rebleeding benefits are most pronounced in patients with these high-risk endoscopic findings 1

Alternative Dosing Considerations

• While some research suggests lower doses (40 mg bolus, 4 mg/hour) may be non-inferior, guidelines consistently recommend the high-dose regimen (80 mg bolus, 8 mg/hour) to prioritize the demonstrated mortality benefit 1, 4
• For hemodynamically stable patients with low-risk findings, IV push dosing (40 mg every 12 hours) may be considered, but this deviates from guideline recommendations for high-risk lesions 5
• Asian populations may potentially use lower infusion doses due to CYP2C19 polymorphisms affecting PPI metabolism, but this requires individualized consideration 3

Critical Caveats

• This dosing protocol applies specifically to non-variceal upper GI bleeding—it has no role in diverticular bleeding or other lower GI bleeding sources 6
• For variceal bleeding, PPIs play only a minor supportive role, with primary therapies being vasoactive drugs, antibiotics, and endoscopic band ligation 1
• Patients with significant comorbidities may experience higher rebleeding rates despite optimal PPI therapy and may benefit from extended infusion beyond 72 hours 3
• Test all patients for H. pylori infection and provide eradication therapy if positive to prevent recurrent ulceration 1, 2

Long-Term Management

• Long-term PPI therapy beyond 6-8 weeks is not recommended unless the patient has ongoing NSAID use or other specific indications 1
• For patients requiring cardiovascular prophylaxis, restart aspirin within 7 days (as soon as cardiovascular risks outweigh GI risks) and continue PPI therapy 2
• Aspirin plus PPI is preferred over clopidogrel alone to reduce rebleeding risk 2