What is the role of proton-pump inhibitors (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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The relative efficacy of proton-pump inhibitors (PPIs) may be due to their superior ability to maintain a gastric pH at a level above 6.0, thereby protecting an ulcer clot from fibrinolysis. [78]  Current guidelines recommend a regimen of an intravenous (IV) PPI 80-mg bolus, followed by a continuous infusion of 8 mg/hour for 72 hours. [79, 80, 81, 82, 83]

Lau et al demonstrated that high-dose IV omeprazole can accelerate the resolution of the stigmata of recent hemorrhage and reduce the need for endoscopic therapy. [84] Barkun et al showed this therapy to be cost-effective. [85] Laine et al demonstrated that high-dose IV lansoprazole, as well as orally administered high-dose lansoprazole, can maintain the intragastric pH above 6. [86]

A meta-analysis of 24 randomized controlled trials that evaluated PPIs for bleeding ulcers (with or without endoscopic therapy) found a significant reduction in the risk of rebleeding, the need for repeat endoscopic hemostasis, and surgery. An improvement in mortality was also seen in Asian trials and in patients with active bleeding or nonbleeding visible vessels. [87]

A systematic review of six randomized trials comprising 2223 patients to assess the use of a PPI before endoscopic evaluation found that pre-endoscopy PPI therapy did not significantly reduce mortality, rebleeding, or the requirement for surgery. [88] However, there was a significantly lower proportion of peptic ulcers with high-risk stigmata at endoscopy and significantly lower rates of endoscopic treatment.

The 2010 international consensus guidelines on upper gastrointestinal (GI) bleeding (UGIB) recommended the use of IV PPIs in all patients with high-risk lesions post endoscopic therapy; PPI therapy might downgrade the lesion if given pre-endoscopy. [89]

Standard daily-dose oral PPIs may be used in patients who do not have active bleeding or other high-risk stigmata for recurrent bleeding (eg, a visible vessel, adherent clots); in such patients, the risk of recurrent bleeding is low. [65] The goal of treatment in these patients (following resuscitation) should be directed at healing the ulcers and at eliminating precipitating factors (eg, H pylori, nonsteroidal anti-inflammatory drugs [NSAIDs]).

When possible, it is important to take biopsy samples to test for H pylori at the initial endoscopy procedure. Because starting high-dose IV PPI therapy is the mainstay of initial management in UGIB, it is difficult to obtain the initial endoscopic biopsies without the presence of ongoing proton-pump inhibition. It is not well understood whether short-duration proton-pump inhibition alters the sensitivity of biopsies for H pylori. Biopsy specimens should be histologically evaluated when the rapid urease test is negative. [45]

A combined analysis of five studies that evaluated oral dosing with PPI (with or without endoscopic therapy) found a significant reduction in the risk of rebleeding and surgery. [90]

NOTE:  Patients with liver cirrhosis may have an increased mortality if treated with PPIs. [91, 92]

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