R.E.B.E.L. EM – The Good, The Bad, and The Ugly of Proton Pump Inhibitors in UGIB

Originally published at R.E.B.E.L. EM on February 23, 2017. Reposted with permission.

Follow Dr. Salim R. Rezaie at @srrezaie 

Upper gastrointestinal bleeding remains a common reason for emergency department visits and is a major cause of morbidity, mortality, and medical care costs. Often when these patients arrive, the classic IV-O2-Monitor is initiated and hemodynamic stability is assessed. One of the next steps often performed includes the initiation of proton pump inhibitors (PPIs).

The ultimate question however is does initiation of PPIs reduce clinically relevant outcomes (i.e. mortality, rebleeding, need for surgical intervention) in upper gastrointestinal bleeds (UGIB)?

Study #1 (The Good) [1]:

  • What They Did:
    • Meta-analysis of  21 randomized controlled trials comprising 2,915 patients
    • Comparison of PPI vs placebo or H2 receptor antagonist in endoscopically proven bleeding ulcer
  • Outcomes Measured:
    • Mortality
    • Rebleeding
    • Surgical intervention
  • Results:
    • PPI treatment significantly reduced rates of:
    • Surgical intervention: 8.4% on PPI vs 13.0% control
    • Rebleeding: 10.6% on PPI vs 18.7% with control
    • NO significant difference in mortality rates between PPI vs control
  • Take Home Point:
    • PPI treatment in endoscopically proven peptic ulcer bleeding reduces rebleeding and surgical intervention rates, but has no effect on mortality.

Study #2 (The Bad) [2]:

  • What They Did:
    • Meta-analysis of six RCTs comprising 2,223 participants with undifferentiated UGIB, undergoing active treatment with a PPI vs control (placebo or H2 blocker)
  • Outcomes Evaluated at 30 Days:
    • Mortality
    • Rebleeding
    • Surgery
    • Stigmata of recent hemorrhage
    • Length of hospital stay
    • Blood transfusion requirements
  • Results:
    • No statistically significant differences in mortality, rebleeding, or surgery between PPI and control treatment
    • Not sufficient evidence to assess for amount of blood transfused or decrease in hospitalized days
  • Take Home Point:
    • PPI treatment initiated before endoscopy for undifferentiated UGIB reduces stigmata of recent hemorrhage and requirement for endoscopic therapy (surrogate outcomes), but DOES NOT affect clinically important, patient centered outcomes namely: mortality, rebleeding, or need for surgery.

Study #3 (The Ugly) [3]:

  • What They Did:
    • Meta-analysis of thirteen RCTs undergoing active treatment with a PPI bolus vs PPI bolus + infusion
  • Outcomes Evaluated:
    • Rebleeding within 7 days
    • Need for urgent intervention
    • Mortality
    • PRBC transfusion
    • Length of hospital stay
  • Results:
    • No statistically significant differences in rebleeding at 7d, mortality prbc transfusion, or hospital length of between PPI bolus and PPI bolus + drip
  • Take Home Point:
    • PPI bolus is just as good as PPI bolus + drip in PUD UGIB

Clinical Bottom Line:

PPI bolus treatment in undifferentiated UGIB DOES NOT improve mortality,* but in the subcategory of proven PUD may improve clinically relevant outcomes such as rebleeding and need for surgical intervention.

* Interestingly, The NNT did a review of this meta-analysis and found that PPIs may have a mortality benefit in the Asian populations and more harmful (or unhelpful) in the European studies.

For More on This Topic Checkout:


  1. Leontiadis GI et al. Proton Pump Inhibitor Treatment for Acute Peptic Ulcer Bleeding. Cochrane Database Syst Rev 2004; (3): CD002094. PMID: 15266462
  2. Sreedharan A et al. Proton Pump Inhibitor Treatment Initiated Prior to Endoscopic Diagnosis in Upper Gastrointestinal Bleeding (Review). Cochrane Database Syst Rev 2010; (7): CD005415. PMID: 20614440
  3. Sachar H et al. Intermittent vs Continuous Proton Pump Inhibitor Therapy for High-Risk Bleeding Ulcers: A systematic Review and Meta-Analysis. JAMA Intern Med 2014; 174(11): 1755 – 62. PMID: 25201154

Post Peer Reviewed By: Anand Swaminathan (Twitter: @EMSwami)

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