What is the comparison between proton pump inhibitor (PPI) continuous infusion and twice daily (BID) dosing in the management of bleeding peptic ulcer?

From the Guidelines

For patients with bleeding ulcers, particularly those with high-risk stigmata who have undergone successful endoscopic therapy, continuous proton pump inhibitor (PPI) infusion is recommended over twice-daily (BID) dosing. This approach is supported by the most recent and highest quality evidence, including the 2019 guideline recommendations from the international consensus group published in the Annals of Internal Medicine 1. The standard regimen involves an 80mg IV bolus of pantoprazole, esomeprazole, or omeprazole followed by 8mg/hour continuous infusion for 72 hours, as this maintains a consistently high gastric pH above 6, which stabilizes blood clots, reduces rebleeding risk, and decreases the need for surgical intervention or repeat endoscopy.

The choice between continuous infusion and BID dosing should be based on the patient's risk stratification, with high-risk features including active bleeding, visible vessels, adherent clots, and hemodynamic instability warranting the more aggressive continuous infusion approach. After the initial 72-hour period, patients can transition to oral PPI therapy, such as pantoprazole 40mg BID, for lower-risk patients or after successful endoscopic hemostasis. The evidence from 1 and 1 supports the use of high-dose intravenous PPI therapy after successful endoscopy, reducing rebleeding, surgery, and mortality in patients with high-risk stigmata.

Key points to consider:

• High-risk patients with active bleeding or high-risk stigmata benefit from continuous PPI infusion.
• The standard regimen is an 80mg IV bolus followed by 8mg/hour continuous infusion for 72 hours.
• Oral PPI therapy can be used after the initial period or in lower-risk patients.
• The choice of treatment should be based on patient risk stratification.
• High-dose intravenous PPI therapy has been shown to reduce rebleeding, surgery, and mortality in high-risk patients 1.

From the Research

PPI Drip vs Bid Dosing in Bleeding Ulcer

• The effectiveness of PPI drip versus bid dosing in bleeding ulcer treatment has been studied in several research papers 2, 3, 4, 5, 6.
• A study published in 2012 found that high-dose intravenous PPI therapy is effective in preventing ulcer rebleeding after endoscopic hemostasis 2.
• Another study published in 2014 compared intermittent PPI therapy with bolus plus continuous-infusion PPI regimen and found that intermittent PPI therapy is comparable to the current guideline-recommended regimen in patients with endoscopically treated high-risk bleeding ulcers 3.
• However, a study published in 2020 found that IV bolus therapy showed worse outcomes compared with continuous IV PPI therapy for patients with peptic ulcer bleeding with high-risk features 4.
• A retrospective study published in 2007 found that high-dose omeprazole reduced the occurrence of rebleeding, need for surgery, and mortality due to hemorrhagic shock in patients with high-risk peptic ulcer bleeding, as compared with standard-dose omeprazole 5.
• Another study published in 2008 found that maximum acid inhibition with a bolus and then a continuous infusion of pantoprazole does not yield better results than treatment with conventional doses in acute hemorrhagic episodes 6.

Key Findings

• High-dose intravenous PPI therapy is effective in preventing ulcer rebleeding after endoscopic hemostasis 2.
• Intermittent PPI therapy is comparable to the current guideline-recommended regimen in patients with endoscopically treated high-risk bleeding ulcers 3.
• Continuous IV PPI therapy may be more effective than IV bolus therapy in patients with peptic ulcer bleeding with high-risk features 4.
• High-dose omeprazole may reduce the occurrence of rebleeding, need for surgery, and mortality due to hemorrhagic shock in patients with high-risk peptic ulcer bleeding 5.

Comparison of PPI Regimens

• Bolus plus continuous-infusion PPI regimen versus intermittent PPI therapy: intermittent PPI therapy is comparable to the current guideline-recommended regimen 3.
• Continuous IV PPI therapy versus IV bolus therapy: continuous IV PPI therapy may be more effective than IV bolus therapy in patients with peptic ulcer bleeding with high-risk features 4.
• High-dose omeprazole versus standard-dose omeprazole: high-dose omeprazole may reduce the occurrence of rebleeding, need for surgery, and mortality due to hemorrhagic shock in patients with high-risk peptic ulcer bleeding 5.