Vascular norepinephrine responsiveness index for early risk stratification in emergency department septic shock: a real-world cohort study from a Latin American sepsis code registry.

BACKGROUND: Septic shock is characterized by heterogeneous vascular responsiveness to norepinephrine. The vascular norepinephrine responsiveness index (VNERi), calculated as diastolic arterial pressure divided by the product of norepinephrine dose and heart rate, has been proposed as a bedside risk-stratification marker. Its performance in routine emergency department care remains uncertain.

METHODS: We conducted a single-center retrospective cohort study of adults with septic shock treated with norepinephrine in the emergency department from 2023 to 2025. The index time was the first protocolized invasive hemodynamic assessment after norepinephrine initiation. The primary outcome was 28-day in-hospital mortality. Logistic regression evaluated the association between VNERi and mortality, adjusting for age, Sequential Organ Failure Assessment score, Charlson comorbidity index, and serum lactate. Discrimination was compared with that of the mean arterial pressure-to-norepinephrine dose ratio (MAP/NE) using paired receiver operating characteristic curves. Non-linearity was assessed using restricted cubic splines. The previously reported value of 6.7 and a cohort-specific cutoff derived using the Youden index were explored.

RESULTS: Among 238 patients, 70 experienced 28-day in-hospital mortality. Median age was 72 years, 52.9% were female, median Charlson comorbidity index was 4, and mean Sequential Organ Failure Assessment score was 7.4. Each 1-unit increase in VNERi was independently associated with lower odds of mortality (adjusted odds ratio, 0.85; 95% CI, 0.79-0.91). VNERi showed modestly greater discrimination than MAP/NE (AUROC, 0.737 [95% CI, 0.675-0.799] vs. 0.667 [95% CI, 0.592-0.742]; p = 0.012). The spline model fit better than the linear specification (p = 0.014). Mortality was 48.0% with VNERi <6.7 and 8.8% with VNERi ≥6.7. The cohort-specific cutoff of 7.6 provided only a marginally higher Youden index than 6.7 (0.475 vs. 0.470).

CONCLUSIONS: Lower VNERi was independently associated with higher 28-day in-hospital mortality and showed modestly greater discrimination than MAP/NE. Prospective multicenter validation using standardized measurement timing and external validation of candidate thresholds are required before clinical implementation.