Efficacy of Acid-Suppressive Therapy for CIGB Prevention in ICU Patients: An Umbrella Review

Introduction: Clinically important gastrointestinal bleeding (CIGB) is a frequent complication in critical patients, typically prevented with stress ulcer prophylaxis using proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs). This umbrella review synthesizes evidence from meta-analyses comparing the effectiveness of PPIs and H2RAs in reducing CIGB in adult ICU populations.


Methods: This umbrella review synthesized evidence from four published meta-analyses evaluating the efficacy of PPIs and H2RAs in preventing CIGB and reducing mortality in ICU population. A comprehensive search of PubMed, Embase, Scopus, and Web of Science was conducted through April 2025. Included reviews were assessed for population scope, overlap, and quality using the AMSTAR-2 tool. Effect estimates were extracted directly as reported and presented as relative risks (RRs), odds ratios (ORs), and 95% confidence or credible intervals (CIs/CrIs).


Results: The Cochrane review by Toews et al. (2018), which included PPIs, H2RAs, sucralfate, and antacids compared to placebo or no prophylaxis, showed a significant reduction in CIGB (RR 0.47; 95% CI, 0.39–0.57). Daou et al. (2022), focusing on neurocritical care patients, reported similar benefits: PPIs (RR 0.37; 95% CI, 0.23–0.59) and H2RAs (RR 0.42; 95% CI, 0.30–0.58) both reduced CIGB versus placebo. Wang et al. (2020, BMJ) found that in general ICU patients, PPIs (OR 0.61; 95% CI, 0.42–0.89) and H2RAs (OR 0.46; 95% CI, 0.27–0.79) reduced CIGB compared to placebo. Wang et al., in their updated 2020 analysis (Intensive Care Medicine) incorporating PEPTIC trial data, confirmed these effects: PPIs vs placebo (RR 0.46; 95% CrI, 0.29–0.66), H2RAs vs placebo (RR 0.67; 95% CrI, 0.48–0.94), and PPIs vs H2RAs (RR 0.69; 95% CrI, 0.45–0.93). No significant differences in all-cause mortality were observed between intervention and control groups across the meta-analyses included.


Conclusions: Both PPIs and H2RAs are effective in reducing the risk of CIGB in critically ill patients, with PPIs demonstrating greater relative efficacy. These findings support the continued use of pharmacologic prophylaxis for gastrointestinal bleeding prevention in ICU settings.