Norepinephrine Dose Threshold at Vasopressin Initiation and Its Association With ICU Mortality in Septic Shock

Background: The optimal norepinephrine (NE) dose at which vasopressin should be initiated in septic shock remains unclear. Current recommendations rely largely on expert consensus rather than robust clinical data. Methods: We conducted a retrospective observational cohort study in a tertiary ICU from 2022–2025 to determine whether initiating vasopressin at lower NE doses is associated with improved ICU outcomes in patients with septic shock. Patients who received both NE and vasopressin were included. A random derivation subset (n = 93) was used to identify the optimal NE dose cutoff for ICU mortality by means ROC curve and Youden index. This threshold was applied to the remaining validation cohort (n = 127). Multivariable logistic regression models were used to assess ICU mortality and renal failure. Results: Of 250 eligible patients, 220 were included. The optimal NE cutoff was 0.40 μg/kg/min (AUC: 0.82; sensitivity: 62.8%, specificity: 87.3%). In the validation cohort, patients receiving vasopressin at NE doses >0.40 μg/kg/min had higher ICU mortality (80% vs. 21%, p < 0.001) and increased renal replacement therapy use (58% vs. 27%, p < 0.001). After adjustment, vasopressin initiation at NE ≤0.40 μg/kg/min was independently associated with reduced ICU mortality (OR, 0.25; 95% CI, 0.07–0.90) and lower risk of renal failure (OR, 0.37; 95% CI, 0.15–0.89), suggesting a protective effect of earlier vasopressin use. Conclusions: Initiating vasopressin at NE doses ≤0.40 μg/kg/min may be associated with improved ICU survival and reduced renal dysfunction. These findings support the use of practical NE thresholds in vasopressor management and complement recent data-driven and meta-analytic evidence.