Source: Sreedharan A, Martin J, Leontiadis GI, Dorward S, Howden CW, Forman D, Moayyedi P. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2010 Jul 7;7:CD005415. Review. PubMed PMID: 20614440.

Efficacy Endpoints: Major Endpoints: Mortality, Re-bleeding, Need for surgical intervention.
Minor Endpoints: Need for endoscopic hemostasis, Blood transfusion, Decrease in Hospital Days.

Harm Endpoints: Delaying definitive diagnosis and treatment, direct cost to patient, indirect cost (change in level of care, nursing care, emergency department flow, etc.)

Narrative: Acute upper gastrointestinal bleeding is a potentially life threatening condition that can demand aggressive intervention from the emergency physicians. Although bleeding can originate in any area above the ligament of Treitz, the majority of bleeding is from a peptic ulcer1,2. Proton pump inhibitors (PPIs) work by reducing gastric acid secretion, neutralizing gastric pH, increasing clot formation3 and decreasing clot lysis4. Intravenous proton pump inhibitors have traditionally been used after endoscopic hemostasis and are believed to prevent re-bleeding and decrease the need for surgery5. Patients with undifferentiated upper GI bleed, however, are often also placed on continuous PPI therapy prior to endoscopy6. This practice can delay definitive diagnosis and endoscopic treatment. Since 37-45% of undifferentiated upper GI bleed is not from a peptic ulcer1,2 patients can be subject to unnecessary medications and cost.

Four randomized control trials comprising of almost 1500 patients were included in the analysis. In this systematic review, PPIs failed to reduce death, re-bleeding rates, or the need for surgery. They did reduce the incidence of high risk lesions found during endoscopic evaluation. There was not sufficient evidence to assess for amount of blood transfused or decrease in hospitalized days, though one trial in the review and one recent trial (citation) showed that there was no difference in either.

Caveats: There were a relatively small number of patients in the PPI group (about 760) and there is a male preponderance in most of the studies. Though studies were conducted in both Asia and Europe, the relatively low numbers might limit generalizability. Also, a decrease in high risk stigmata on endoscopic evaluation may represent a clinically useful outcome if it reduced the need for hemostatic intervention. A study by Lau1 showed that there was a 14% reduction in endoscopic hemostasis in the PPI group, with a number needed to treat to prevent one intervention of 7.

Author: Koustav Mukherjee, MD

Published/Updated: January 7, 2010