Histamine-2-Receptor Antagonist Administration and Gastrointestinal Bleeding When Used for Stress Ulcer Prophylaxis in Patients With Severe Sepsis or Septic Shock

Background: The Surviving Sepsis Campaign suggests that proton pump inhibitors (PPIs) be considered over histamine-2-receptor antagonists (H2RA) for stress ulcer prophylaxis (SUP), but there are no studies demonstrating superiority with PPIs in this population. Objective: To determine if H2RAs are associated with an increased risk for gastrointestinal (GI) bleeding in patients with severe sepsis or septic shock. Methods: This study queried the Multiparameter Intelligent Monitoring in Intensive Care II database to identify adult patients with severe sepsis or septic shock requiring mechanical ventilation for at least 48 hours. Patients were excluded if they had GI bleeding as a primary diagnosis, variceal bleeding, received both PPIs and H2RAs or no acid suppression. Demographic characteristics, medication use and potential confounders for GI bleeding were recorded. ICD-9 coding was used to identify GI bleeding listed as a secondary diagnosis. Multivariate analysis was performed to assess the role of H2RAs as an independent risk factor for GI bleeding. Results: There were 686 patients evaluated. The incidence of GI bleeding was 9.5%. Patients who received H2RAs had a bleeding incidence of 2.3% versus 10% with PPIs (P = 0.111). On controlling for confounding variables, drug selection (H2RA or PPI) was not associated with an increased risk for bleeding. Acute or chronic liver disease was the only independent risk factor identified: odds ratio [OR] (95% CI) = 3.75 (2.19-6.44); P < 0.001. Conclusion: H2RAs are not associated with an increased risk for GI bleeding in patients with severe sepsis or septic shock who require mechanical ventilation. These data do not support the Surviving Sepsis Campaign recommendation of PPIs as the preferred agent in this population.