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

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 mu g/kg/min) and normal (last norepinephrine dose >= 0.25 mu g/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.