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:
- Ken Milne: at The SGEM: SGEM #16 – Ho, Ho, Hold the Proton Pump Inhibitor in Upper Gastrointestinal Bleed
- Salim Rezaie at ALiEM: Upper Gastrointestinal Bleeding – Evidence Based Treatment
References:
- Leontiadis GI et al. Proton Pump Inhibitor Treatment for Acute Peptic Ulcer Bleeding. Cochrane Database Syst Rev 2004; (3): CD002094. PMID: 15266462
- 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
- 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)
The post The Good, The Bad, and The Ugly of Proton Pump Inhibitors in UGIB appeared first on REBEL EM - Emergency Medicine Blog.