Early administration of multiple vasopressors is associated with better survival in patients with sepsis: a propensity score-weighted study

Abstract

Background: The association between the timing of administration of multiple vasopressors and patient outcomes has not been investigated. Methods: This study used data from the MIMIC-IV database. Patients with sepsis who were administered two or more vasopressors were included. The principal exposure was the last norepinephrine dose when adding a second vasopressor. The cohort was divided into early (last norepinephrine dose < 0.25 μg/kg/min) and normal (last norepinephrine dose ≥ 0.25 μg/kg/min) groups. The primary outcome was 28-day mortality. Multivariable Cox analyses, propensity score matching, stabilized inverse probability of treatment weighting (sIPTW), and restricted cubic spline (RCS) curves were used. Results: Overall, 1,437 patients who received multiple vasopressors were included. Patients in the early group had lower 28-day mortality (HR: 0.76; 95% CI: 0.65–0.89; p < 0.001) than those in the single group, with similar results in the propensity score-matched (HR: 0.80; 95% CI: 0.68–0.94; p = 0.006) and sIPTW (HR: 0.75; 95% CI: 0.63–0.88; p < 0.001) cohorts. RCS curves showed that the risk of 28-day mortality increased as the last norepinephrine dose increased. Conclusions: The timing of secondary vasopressor administration is strongly associated with the outcomes of patients with sepsis.