Optimal epinephrine injection volume in acute peptic ulcer bleeding. A systematic review and meta-analysis

Endoscopic treatment improves the outcomes of patients with acute peptic ulcer bleeding (APUB). Epinephrine injection is a frequently used treatment. There is no consensus, however, on the optimal volume of epinephrine injection. Primary aim was to compare the efficacy and safety of endoscopic injection using different volumes of epinephrine for APUB treatment in a systematic review and meta-analysis.

Systematic searches were performed for full papers published from 1986 until January 2025 in multiple databases. We included randomized controlled trials (RCT) comparing different epinephrine volumes injection. Primary outcome was permanent haemostasis defined as achieved initial haemostasis and not rebleeding during admission. Secondary outcomes were adverse events, need for rescue treatment and mortality. We estimated the OR and 95%CI using random-effects models.

Four RCT including 556 patients were analyzed. No studies comparing different doses of epinephrine in combination therapy were found. In studies comparing different doses of epinephrine alone, permanent haemostasis was more frequently achieved in the large-volume injection groups (91% vs 77%, OR:2.90; 95%CI:1.72-4.86, p<0.0001). Adverse events (AE) were also more frequent in the large-volume groups (33% vs 3%, OR: 21.02; 95%CI:6.51-67.87, p<00001). Abdominal pain was the most frequent AE. Bowel perforation appeared only when injection volumes exceeded 35 cc.

Endoscopic injection of large volumes of epinephrine up to 30cc appear safe and improve rates of permanent haemostasis when compared to lower injection volume in patients with APUB. Trials assessing the use of larger epinephrine volume in combination endoscopic hemostatic therapy are needed.