Do we use Proton Pump Inhibitors (PPIs) in cases of variceal or peptic ulcer bleeding?

PPI Use in Variceal vs Peptic Ulcer Bleeding

PPIs are strongly recommended for peptic ulcer bleeding with high-dose infusion (80 mg bolus followed by 8 mg/hour for 72 hours) after endoscopic hemostasis, while in variceal bleeding, PPIs can be used following endoscopic treatment to prevent post-procedure ulcer bleeding, though the evidence is weaker and vasoactive agents (octreotide/somatostatin) remain the primary pharmacologic therapy. 1, 2

Peptic Ulcer Bleeding: Strong Indication for PPIs

Initial Management

• Start PPI therapy as soon as possible, even before endoscopy, to potentially reduce stigmata of recent bleeding and the need for endoscopic therapy 1, 2
• The mechanism is clear: gastric pH above 6 is necessary for platelet aggregation and clot stability, and blood clot stability is reduced in acidic environments 1

Dosing Protocol for Peptic Ulcer Bleeding

• 80 mg IV bolus followed by 8 mg/hour continuous infusion for 72 hours after successful endoscopic hemostasis 1, 2
• High-dose intravenous PPIs significantly reduce rebleeding (5.9% vs 10.3%, p=0.03) and need for endoscopic retreatment compared to placebo 2, 3
• After 72 hours, transition to oral PPI therapy for 6-8 weeks to allow complete mucosal healing 1, 2

Important Caveats

• While some meta-analyses show no difference between high-dose and non-high-dose PPIs 4, the most recent guidelines still recommend high-dose regimens based on randomized controlled trial data showing benefit 2, 1
• Long-term PPI is not recommended unless ongoing NSAID use exists 2, 1

Variceal Bleeding: Limited Role for PPIs

Primary Therapy is NOT PPIs

• Vasoactive agents (octreotide or somatostatin analogs) are the recommended pharmacologic therapy for portal hypertensive bleeding, not PPIs 2
• Octreotide/somatostatin use was associated with 30 fewer deaths per 1,000 patients compared to placebo (RR 0.85,95% CI 0.72-1.00) 2

When PPIs Are Used in Variceal Bleeding

• PPIs can be used following endoscopic treatments (such as band ligation or cyanoacrylate injection) to prevent post-procedure ulcer bleeding 2
• The Korean Association for the Study of the Liver gives this a B2 recommendation (weak evidence) 2
• One retrospective study showed PPI use decreased rebleeding risk following endoscopic variceal obliteration (OR 0.554,95% CI 0.352-0.873) 2
• PPI treatment following EVL may be effective in healing post-EVL ulcers 5

Critical Distinction

• In variceal bleeding, approximately 30% of upper GI bleeding in cirrhotic patients is actually from peptic ulcers, not varices 2
• PPIs are recommended for the peptic ulcer component, not for the variceal bleeding itself 2
• One randomized trial showed that after successful EVL, PPI infusion was similar to vasoconstrictor infusion in preventing very early rebleeding (2% vs 2%, p=1.0), but this was for post-procedure ulcer prevention, not variceal hemostasis 6

Practical Algorithm

For Suspected Upper GI Bleeding:

1. Start high-dose PPI immediately (covers both peptic ulcer and post-endoscopic therapy needs) 1, 2
2. If cirrhosis/portal hypertension suspected, add octreotide or somatostatin 2
3. Perform endoscopy within 12 hours 2
4. If peptic ulcer confirmed: Continue high-dose PPI infusion for 72 hours, then oral PPI for 6-8 weeks 1, 2
5. If variceal bleeding confirmed: Continue vasoactive agents for 2-5 days; consider continuing PPI to prevent post-procedure ulcer bleeding 2, 6

Common Pitfalls

• Do not rely solely on PPIs for active variceal bleeding—endoscopic therapy plus vasoactive agents are essential 2
• Long-term PPI use in cirrhotic patients can increase risk of spontaneous bacterial peritonitis and hepatic encephalopathy 2
• Discontinuing PPI too early (before 6-8 weeks) in peptic ulcer bleeding may not allow adequate mucosal healing 1
• Failure to test for H. pylori in peptic ulcer bleeding leads to recurrence rates of 40-50% over 10 years 1