Mean arterial pressure-to-norepinephrine-equivalent dose ratio, rather than achieved mean arterial pressure alone, is associated with mortality in septic shock

Higher mean arterial pressure (MAP) is commonly pursued in septic shock, yet randomized trials have failed to demonstrate a survival benefit—and patients achieving higher MAP often exhibit paradoxically greater mortality. We hypothesized this reflects impaired vascular responsiveness requiring greater vasopressor support, quantifiable by the MAP-to-norepinephrine-equivalent dose ratio (MAP/NEQ). We conducted a retrospective cohort study using two independent critical care databases (MIMIC‑IV and eICU). Adult patients with septic shock receiving vasopressors within 24 h of ICU admission were included. The primary exposure was the 24-h time-weighted average MAP (65–80 mmHg vs. ≥ 80 mmHg); the key secondary exposure was MAP/NEQ. The primary outcome was 28-day mortality. Cox regression, restricted cubic splines, and mediation analysis were performed. A total of 7433 patients were included (MIMIC‑IV: n = 4944; eICU: n = 2489). Despite being younger with fewer comorbidities, patients with MAP ≥ 80 mmHg had higher 28-day mortality (MIMIC-IV: 19.5% vs. 12.6%; eICU: 20.5% vs. 11.0%; both P < 0.001). After adjustment for MAP/NEQ, the association between high MAP and mortality became non-significant, while MAP/NEQ remained independently and inversely associated with mortality in both cohorts (AUC 0.81 and 0.72). Mediation analyses revealed a suppression effect (− 33% and − 26%), indicating higher MAP coexisted with impaired vascular responsiveness. Subgroup and sensitivity analyses were consistent. Higher achieved MAP was not independently associated with 28-day mortality after accounting for vascular responsiveness. MAP/NEQ may serve as a clinically accessible tool for early risk stratification and identification of a vasoplegic phenotype in septic shock, though prospective validation is needed before clinical application.