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Research Snapshot Theater: Pharmacology/Quality and Patient Safety, Adult II

Mortality of Histamine-2 Receptor Antagonists vs Proton Pump Inhibitors in the ICU: A Meta-Analysis

Monday, March 23, 2026
10:15 AM - 11:15 AM Central Time
Location: Connections Central - RST 11

  • Carla Erb, DO

    Disclosure(s): No relevant financial relationship(s) to disclose.

  • HK

    Hanna Kim, M.S

    Statistical consultant
    University of Georgia

    Disclosure information not submitted.

  • JL

    Jinae Lee, PhD

    Associate Director of the UGA Statistical Consulting Center
    University of Georgia

    Disclosure information not submitted.

  • MM

    Marina M. Mina, MD

    Resident Physician
    AU/UGA Medical Partnership

    Disclosure information not submitted.

  • ST

    Shraddha Tongia, MD

    Pulmonologist
    Athens Pulmonary and Sleep Medicine

    Disclosure information not submitted.

Introduction: Stress ulcer prophylaxis (SUP) is a standard intervention in intensive care units (ICUs), routinely recommended to prevent upper gastrointestinal (GI) bleeding and stress-related ulcers in critically-ill patients. To reduce the risk, guidelines recommend either proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) as first-line options for SUP in ICU patients, however, the effect on mortality between these two is not well established. The goal of this meta-analysis is to assess overall mortality, when comparing the use of H2RAs or PPIs in critically-ill patients requiring stress ulcer prophylaxis.


Methods: A systematic search of PubMed, Cochrane Library, and Google Scholar was conducted for trials reporting the mortality in critically-ill patients on either a proton pump inhibitor or a histamine 2 receptor antagonist. Studies were selected by two independent reviewers. Data was analyzed using meta-analysis, with the mortality risk ratio (RR) as the measure of effect.


Results: Eight studies enrolling a total of 32,877 patients were included. Mortality was significantly lower in the H2RA group compared to that of the PPI group (RR 0.84; 95% CI 0.73–0.97; P = 0.0183). Subgroup analysis restricted to studies reporting 90-day mortality was also significantly lower in the H2RA group compared to the PPI group (RR 0.84; 95% CI 0.71–0.99; P = 0.0408).


Conclusions: In critically-ill patients receiving stress ulcer prophylaxis, the mortality was significantly lower in those receiving a H2RA compared to those receiving a PPI. The study findings suggest that H2RAs may offer a survival advantage in the ICU setting and should prompt re-evaluation of practice patterns. It also enforces the need for standardized drug-specific guidelines on SUP. Future research should focus on mortality as well as other potential side-effects between SUP medications. Practitioners should, in the meantime, consider starting patients on a H2RA, and escalating to a PPI if clinically indicated.