Continuous Infusion Versus Intermittent Bolus Proton Pump Inhibitor Therapy Following Endoscopic Hemostasis for Bleeding Peptic Ulcers: A Systematic Review and Meta-Analysis

Background/Objectives: Continuous high-dose intravenous proton pump inhibitor (PPI) infusion is commonly used following endoscopic hemostasis for bleeding peptic ulcers, despite uncertainty regarding its clinical advantage over intermittent administration. This systematic review and meta-analysis evaluated whether continuous infusion improves clinically relevant outcomes compared with intermittent intravenous bolus therapy. Methods: A systematic search of PubMed, Scopus, Web of Science, ScienceDirect, and Embase was conducted from inception through to 29 June 2026 to identify randomized controlled trials. Effect estimates were pooled using random-effects models with restricted maximum-likelihood estimation and Hartung-Knapp adjustment. Risk of bias was assessed using RoB 2 and certainty of evidence using GRADE. The protocol was retrospectively registered on OSF. Results: Twelve randomized controlled trials involving 1726 participants were included. Across 11 trials (1621 participants), the pooled estimate did not demonstrate a statistically significant reduction in overall rebleeding with continuous infusion compared with intermittent bolus therapy (RR 0.93, 95% CI 0.65-1.35; I2 = 1.4%). Likewise, the pooled estimates did not demonstrate superiority of continuous infusion for rebleeding within 24 h (RR 0.70, 95% CI 0.09-5.64), rebleeding within 7 days (RR 1.07, 95% CI 0.66-1.72), surgery (RR 1.42, 95% CI 0.80-2.53), or mortality (RR 1.76, 95% CI 0.90-3.44). Moderate-certainty evidence indicated little or no clinically important difference in blood units transfused or hospital stay. Certainty was very low for rebleeding outcomes and low for surgery and mortality. Conclusions: Continuous intravenous PPI infusion was not shown to be superior to intermittent intravenous bolus therapy following successful endoscopic hemostasis. However, the very low- to low-certainty evidence for rebleeding, surgery, and mortality establishes neither equivalence nor noninferiority and does not exclude clinically important benefit or harm. The available trials do not identify the optimal intermittent dose or dosing frequency.