Efficacy and safety of calcineurin inhibitors (CNIs) for septic patients in ICU: A cohort study from MIMIC database

Abstract

Abstract Background Sepsis is characterized by a dysregulated immune response to infection. Calcineurin inhibitors (CNIs) is a widely used immunosuppressant and has unique properties that may be associated with beneficial outcomes of patients with sepsis by keeping down of an overactive immune response. Our research is designed to investigate whether the use of CNIs exempt septic patients from adverse prognosis and assess whether it might bring about some adverse reactions. Methods The Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV 2.2) database was searched to identify septic patients with and without the use of CNIs. Propensity score matching (PSM) was applied to balance the baseline characteristics between the CNIs group and the non-user group. The primary outcome was 28-day mortality, the relationship between CNIs and patient death was analyzed by Kaplan-Meier method and Cox proportional hazard regression models. Results 22517 patients with sepsis were extracted from the MIMIC IV database. In the propensity score-matched sample of 874 individuals, lower 28-day mortality risks were observed in the CNIs group compared to the non-users’ group (HR: 0.26; 95%CI: 0.17, 0.41) by univariate cox hazard analysis. In addition, the Kaplan-Meier survival curves indicated a significant superior 28- and 365-day survival rate for CNI users compared to non-users (the log-rank test p-value was 0.001). There was no significant association between the use of CNIs and an increased risk of new onset of infection (p = 0.144). Conclusion Calcineurin inhibitors was associated with decreased short- and long-term mortality among septic patients without increased incidence of new onset of infection, hyperkalemia, severe hypertension and AKI, but may generate undesirable reaction such as liver injury and mild hypertension.