What is the efficacy of PPIs in the treatment of upper gastrointestinal bleeding (UGIB)?

Updated: Sep 01, 2021
  • Author: Bennie Ray Upchurch, III, MD, FACP, AGAF, FACG, FASGE; Chief Editor: BS Anand, MD  more...
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There are two approved intravenous (IV) PPIs in use in the United States, pantoprazole (Protonix IV formulation) and esomeprazole magnesium (Nexium IV formulation)

These agents suppress gastric acid secretion by specifically inhibiting the H+/K+/ATPase enzyme system at the secretory surface of gastric parietal cells. Use of the IV preparation has been studied only for short-term therapy (ie, 7-10 d) and may be a useful adjunct via stabilization of the clot by increasing intragastric pH. High-dose IV treatment is the norm; however, high-dose oral therapy may be able to maintain the intragastric pH at about 6 as well. [86]

In severe acute upper GI bleeding (UGIB), IV proton pump inhibition should be initiated once the patient's hemodynamic status has been addressed and appropriate resuscitation measures have been implemented. [132]  Lau and colleagues reported the benefit of a high-dose bolus followed by continuous infusion of omeprazole before patients underwent endoscopy. [156] Endoscopic treatment was required in 19.1% of patients who received omeprazole compared to 28.4% of patients who received placebo (= 0.007). Similarly, among patients with peptic ulcer disease, in the omeprazole group there were fewer patients with active bleeding in omeprazole group (6.4% vs 14.7%; = 0.01) and more had clean-based ulcers  (64.2% vs 47.4%; = 0.001). [156]

A Cochrane systematic review and meta-analysis of six randomized trials (N = 2,223) of pre-endoscopic PPI therapy found no significant differences between the PPI and control groups with respect to mortality (6.1% vs 5.5%), rebleeding (13.9% vs 16.6%), or surgery (9.9% vs 10.2%). [88]  Moreover, PPI therapy significantly reduced the proportion of participants with higher-risk stigmata of hemorrhage (active bleeding, nonbleeding visible vessel, and adherent clot) at index endoscopy (37.2% vs 46.5%) and undergoing endoscopic therapy at index endoscopy (8.6% vs 11.7%). [88]

Another Cochrane meta-analysis of 24 trials comprising 4,373 patients with peptic ulcer bleeding who did not consistently receive endoscopic hemostatic therapy found that PPI therapy was associated with reduced rebleeding and need for surgery surgery, but not mortality except among those at the highest risk. [157] This suggests that if endoscopy will be delayed or cannot be performed, PPI therapy may improve clinical outcomes.

PPI therapy should be discontinued after endoscopy unless the patient has a source for which PPIs may be beneficial (e.g., ulcers and erosions). [65]

The use of H2-receptor antagonists has not been shown to be effective in altering the course of UGIB. A meta-analysis concluded that there was a possible minor benefit with intravenous H2 antagonists in bleeding gastric ulcers but no benefit in duodenal ulcers. [158]

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