Epinephrine injection versus epinephrine injection and a second endoscopic method in high risk bleeding ulcers

Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005584. doi: 10.1002/14651858.CD005584.pub2.


Background: Endoscopic therapy reduces rebleeding rate, need for surgery, and mortality in patients with bleeding peptic ulcers. Injection of epinephrine is the most popular therapeutic method. Guidelines disagree on the need for a second haemostatic procedure immediately after epinephrine.

Objectives: The objective of this review was to determine whether the addition of a second procedure improves efficacy or patient outcomes or both after epinephrine injection in adults with high risk bleeding ulcers.

Search strategy: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which includes the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to February 2006), EMBASE (1980 to February 2006) and reference lists of articles. We also contacted experts in the field.

Selection criteria: Randomised studies comparing endoscopic treatment: epinephrine alone versus epinephrine associated with a second haemostatic method in adults with haemorrhage from peptic ulcer disease with major stigmata of bleeding as defined by the Forrest classification. Bleeding must have been confirmed by endoscopy.

Data collection and analysis: Two authors independently assessed trial quality and extracted data.

Main results: Seventeen studies including 1763 people were included. Adding a second procedure reduced further bleeding rate from 18.8% to 10.4%; Peto Odds Ratio 0.51; 95% confidence interval (CI) 0.39 to 0.66, and emergency surgery from 10.8% to 7.1%; OR 0.63; 95% CI 0.45 to 0.89. Mortality fell from 5% to 2.5% OR 0.50; 95% CI 0.30 to 0.82. Subanalysis showed that the risk of further bleeding decreased regardless of which second procedure was applied. In addition, the risk was reduced in all subgroups.

Authors' conclusions: Additional endoscopic treatment after epinephrine injection reduces further bleeding, the need for surgery and mortality in patients with bleeding peptic ulcer.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Combined Modality Therapy / methods
  • Epinephrine / administration & dosage*
  • Hemostasis, Endoscopic / methods*
  • Humans
  • Peptic Ulcer Hemorrhage / mortality
  • Peptic Ulcer Hemorrhage / prevention & control
  • Peptic Ulcer Hemorrhage / therapy*
  • Randomized Controlled Trials as Topic
  • Secondary Prevention
  • Vasoconstrictor Agents / administration & dosage*


  • Vasoconstrictor Agents
  • Epinephrine