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

Abstract

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.

Keywords

• Sepsis
• Histamine antagonists
• H2RA
• MIMIC database
• ICU
• Mortality