Timing of rebleeding in high-risk peptic ulcer bleeding after successful hemostasis: a systematic review

Peptic ulcer rebleeding (PUR) usually occurs within three days following endoscopic hemostasis. However, recent data have increasingly suggested delayed rebleeding.

To better characterize the timing of PUR (Forrest Ia to IIb) following initially successful endoscopic hemostasis.

An exhaustive literature search (1989 to 2013), with cross-referencing, was performed to identify pertinent randomized controlled trial (RCT) arms. Patients receiving high-dose proton pump inhibitor (PPI) infusion following successful modern-day endoscopic hemostasis were included. A sensitivity analysis included any patients receiving PPI doses >40 mg daily. The main outcome measure was 30-day rebleeding, while weighted mean averages at t = three, seven, 14 and 28 to 30 days are also reported.

Of 756 citations, six RCTs were included (561 patients; 58.5% to 89.5% male; 55.3 to 67.5 years of age). Among patients receiving high-dose PPI (five RCTs [393 patients]), 11.5% (95% CI 8.4% to 14.7%) experienced rebleeding, 55.6% (95% CI 41.1% to 70.1%) rebled within three days, 20% (95% CI 8.3% to 31.7%) between four and seven days, 17.8% (95% CI 6.6% to 28.9%) at eight to 14 days, and 6.7% (95% CI 0% to 14%) at 15 to 28 to 30 days. Using the relaxed lower PPI dosing threshold, similar respective rates were 14.4% (95% CI 11.5% to 17.3%) overall, with interval rates of 39.5% (95% CI 28.9% to 50.15%), 34.6% (95% CI 24.2% to 44.9%), 19.7% (95% CI 11% to 28.4%) and 6.2% (95% CI 0.95% to 11.5%). Qualitative review of patient characteristics, limited by small sample size, possible bias and study heterogeneity, suggested increased patient comorbidity and postendoscopic use of lower PPI dosing may predict delayed rebleeding.

In patients with high-risk PUR undergoing successful endoscopic hemostasis, most rebled within three days, with many experiencing later rebleeding. Additional research is needed to better predict such an outcome.