Early initiation of norepinephrine in patients with septic shock: A propensity score-based analysis

The use of vasopressors is vital in septic shock. However, the optimal timing of treatment remains unclear. Therefore, we aimed to explore the impact of early norepinephrine initiation on the survival of patients with septic shock. We selected 4253 patients from the Medical Information Mart for Intensive Care IV database between 2008 and 2019. The primary outcome was 28-day mortality. Propensity score matching (PSM) was applied to minimize between-group imbalances, and a restricted mean survival time was used to quantify the beneficial impact of early norepinephrine treatment on survival. Sensitivity analyses were conducted to test the robustness of the study results in multiple cohorts. In the PSM cohort, 2862 patients were equally assigned to early (receiving norepinephrine within the first 3 h) and delayed (> 3 h) norepinephrine initiation groups. Patients in the early norepinephrine initiation group received significantly less fluid therapy (0 vs. 79 mL/kg), had lower 28-day mortality (30.0% vs. 37.8%), longer survival days (21.89 vs. 20.37 days), shorter duration of intensive care unit (4.9 vs. 7.2 days) and hospital stays (12.4 vs. 13.6 days), shorter duration of supportive norepinephrine and invasive mechanical ventilation, lower incidence of organ failure progression (64.4% vs. 79.2%) within 24 h after shock onset, and higher mean arterial pressure within 6 and 24 h after shock onset than patients in the delayed norepinephrine initiation group (p < 0.05). Norepinephrine initiation within the first 3 h, regardless of preload dependency, was associated with longer survival time and shorter duration of supportive norepinephrine and invasive mechanical ventilation and may delay or partially reverse rapid onset organ failure. •Norepinephrine (