Proton pump inhibitor boluses as effective as infusions in ulcer bleeds

1. Bleeding ulcers in the stomach and duodenum that are deemed high risk for rebleeding are defined by three endoscopically determined characteristics: active bleeding, visible vessel, or an adherent clot.

2. This meta-analysis suggests that, in these high risk situations, intermittent boluses of proton pump inhibitors (PPI) have the same outcomes as the current standard of care, which includes an initial bolus followed by an intravenous infusion of PPI for 72hrs.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Ulcers are one of the most common causes of gastrointestinal bleeds. Current standard of care in patients with high risk bleeding ulcers is to administer an intravenous bolus of a proton pump inhibitor (PPI), followed by a continuous infusion for 72 hours. However, there is also data to suggest that these patients have an equally favorable outcome with intermittent PPI boluses. This could potentially save significant money and resources. This study, a systematic review and meta-analysis, was done to determine whether intermittent bolus PPI is non-inferior to continuous PPI infusion in patients at high risk of rebleeding. Classically, high risk of bleeding is defined endoscopically, where any one of the following is visualized: active bleeding, visible vessel, or adherent clot.

This meta-analysis suggests that in these high-risk situations, intermittent boluses of a PPI have the same outcomes as continuous PPI infusion. A major strength of this study is that only randomized controlled trials were included, and different databases were used to ensure that all were included in the analysis. Weaknesses of the study, which are present in all meta-analyses, are variations in the study protocol in the different studies, which leads a possible bias in the interpretation. Lastly, the nature of study also cannot provide the optimal PPI bolus doses or length of time, since these were variable in the studies.

Click to read the study, published today in JAMA Internal Medicine

Relevant Reading: Intermittent versus continuous pantoprazole infusion in peptic ulcer bleeding: a prospective randomized study

In-Depth [meta-analysis]: All randomized controlled trials from three bibliographic databases that compared bolus PPI to continuous PPI after endoscopic management of a high risk bleeding ulcer were include in this meta-analysis. No restrictions were placed on the frequency of PPI boluses used in the studies, or route of administration (intravenous or oral). Continuous PPI therapy was an 80 mg intravenous bolus followed by a continuous 8 mg per hour intravenous infusion for 72 hours, which is current standard treatment. The primary outcome was recurrent bleeding within seven days. Secondary outcomes included recurrent bleeding in three days and 30 days. A total of 13 studies were included in this analysis.

The primary population for analysis was per protocol. For the primary outcome of recurrent bleeding within seven days, intermittent PPI therapy was non-inferior to continuous PPI (RR 0.72; 1-sided 95% CI upper boundary 0.97). The same held true for the secondary outcomes: recurrent bleeding in three days (RR 0.73; 1-sided 95% CI upper boundary 1.02) and recurrent bleeding in 30 days (RR 0.89; 1-sided 95% CI upper boundary 1.17). Lastly, the same noninferior result was found for mortality, surgery and radiologic intervention, and hospital length of stay.

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