Comparison of Histamine-2 Receptor Antagonists and Proton Pump Inhibitors for Stress Ulcer Prophylaxis in Patients With Septic Shock

Objectives: To compare the effectiveness of histamine-2 receptor antagonists (H2RAs) vs. proton pump inhibitors (PPIs) for stress ulcer prophylaxis on the occurrence of upper gastrointestinal bleeding (UGIB) and other clinical outcomes in hospitalized patients with septic shock. Design: Retrospective, multicenter, propensity-weighted cohort study. Setting: Conducted across 220 geographically diverse community and teaching hospitals in the United States. Patients: Adult patients (age ≥ 18 yr) with septic shock who were initiated on either H2RAs or PPIs on the day of hospital admission. Interventions: H2RAs (famotidine) or PPIs (pantoprazole, omeprazole, esomeprazole, or lansoprazole). Measurements and Main Results: The primary outcome was the occurrence of UGIB during hospitalization. Secondary outcomes included in-hospital mortality, ventilator-associated pneumonia, Clostridioides difficile infection, and hospital length of stay. Propensity scores with inverse probability of treatment weighting (IPTW) were used to control for confounding. Among 15,102 patients (5,492 H2RA, 9,610 PPI), the mean age was 65.8 ± 14.9 years, 47.8% were female, and 58.1% received invasive mechanical ventilation during hospitalization. After IPTW adjustment, PPI use was associated with a lower occurrence of UGIB compared with H2RA (odds ratio [OR], 0.78; 95% CI, 0.64–0.96; p = 0.016). A sensitivity analysis comparing famotidine to pantoprazole confirmed this finding (OR, 0.80; 95% CI, 0.65–0.97; p = 0.025). No significant differences were observed in in-hospital mortality (OR, 0.98; 95% CI, 0.91–1.06; p = 0.691), ventilator-associated pneumonia (OR, 0.93; 95% CI, 0.83–1.04; p = 0.188), C. difficile infection (OR, 1.32; 95% CI, 0.82–2.13; p = 0.246), or hospital length of stay (incidence rate ratio, 1.01; 95% CI, 0.98–1.05; p = 0.417). Conclusions: In this large, diverse cohort of U.S. hospitalized adults with septic shock, PPI use for stress ulcer prophylaxis was associated with a significantly lower occurrence of UGIB compared with H2RA, with no significant differences in mortality, ventilator-associated pneumonia, C. difficile infection, or hospital length of stay.