Association between histamine 2 receptor antagonists and sepsis outcomes in ICU patients: a retrospective analysis using the MIMI-IV database

Abstract

Background: Sepsis is marked by elevated histamine, which is a vasodilator that increases vascular permeability. Although human studies are lacking, murine models of sepsis have indicated potential protective effects of histamine 2 receptor antagonist administration (H2RAs). Objective: To assess any association between H2RA use in sepsis-3 patients admitted to the ICU and mortality, mechanical ventilation, length of stay, and markers of renal, liver, and lung dysfunction. Design: Retrospective cohort study. Setting: Intensive care units of the Beth Israel Deaconess Medical Center (BIDMC) accessed via the MIMIC-IV database spanning an 11-year period from 2008 to 2019. Patients (or participants): A total of 30,591 patients met the inclusion criteria for sepsis-3 on admission (mean age 66.49, standard deviation 15.92). Main measures: We collected patient age, gender, ethnicity, comorbidities (contained within the Charlson comorbidity index), SOFA score, OASIS score, APS III score, SAPS II score, H2RA use, creatinine, BUN, ALT, AST, and P/F ratios. Primary outcomes were mortality, mechanical ventilation, and ICU length of stay. Key results: A total of 30,591 patients met inclusion criteria over the 11-year sample period. The 28-day in hospital mortality rate was significantly lower among patients who received an H2RA (12.6% vs 15.1%, p < 0.001) as compared to those who did not receive an H2RA. Patients receiving an H2RA had significantly lower adjusted odds of mortality (0.802, 95% CI 0.741–0.869, p < 0.001), but significantly higher adjusted odds of invasive mechanical ventilation (4.426, 95% CI 4.132–4.741, p < 0.001) and significantly higher ICU LOS (3.2 days vs. 2.4 days, p < 0.001) as compared to the non-H2RA group. H2RA use was also associated with decreased severity of acute respiratory distress syndrome (ARDS) and lower serum creatinine. Conclusion: Among patients hospitalized in the ICU for sepsis, the use of an H2RA was associated with significantly lower odds of mortality, decreased severity of ARDS, and a lower incidence of renal insufficiency.