Optimization of norepinephrine dosage for hemodynamic stability during ECMO support in refractory shock: a...

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) serves as a crucial salvage therapy for refractory shock; however, the optimal strategy for vasopressor management during extracorporeal circulatory support remains unclear. Norepinephrine is a cornerstone agent for maintaining perfusion pressure, yet the association between its dose intensity and patient outcomes remains controversial.

This study aimed to investigate the association between the norepinephrine-equivalent dose during the initial phase of VA-ECMO support and clinical outcomes in patients with refractory shock.

In this retrospective cohort study, 135 patients with refractory shock supported by VA-ECMO in the intensive care unit (ICU) of our hospital from January 2020 to January 2025 were included. Patients were divided into a low-dose group (n = 68) and a high-dose group (n = 67) based on the median value of the mean norepinephrine-equivalent dose within 72 h after ECMO initiation. Baseline characteristics, 30-day all-cause mortality, a composite endpoint of hemodynamic stability (proportion of time meeting target thresholds between 24 and 72 h of ECMO support), successful ECMO weaning rate, ICU length of stay, total duration of vasopressor support, and indicators of tissue perfusion and organ function [24 h lactate clearance, Δ Sequential Organ Failure Assessment (SOFA) score, and the incidence of acute kidney injury] were compared between groups.

At baseline, the high-dose group had significantly higher SOFA scores (t = 4.156, p < 0.001) and serum lactate levels (t = 4.893, p < 0.001) compared to the low-dose group. Survival analysis demonstrated a significantly lower 30-day cumulative survival rate in the high-dose group (log-rank χ² = 9.873, p = 0.002). After adjustment using multivariable Cox regression, a high vasopressor dose remained an independent risk factor for mortality (HR = 1.92, 95% CI 1.13-3.25, p = 0.015). Regarding secondary outcomes, the proportion of patients achieving hemodynamic stability was significantly lower in the high-dose group (χ² = 10.897, p = 0.001). This group also exhibited a lower successful ECMO weaning rate (χ² = 8.352, p = 0.004), a longer ICU stay (t = 2.341, p = 0.021), and a prolonged duration of vasopressor support (t = 3.894, p < 0.001). Tissue perfusion metrics revealed that the 24 h lactate clearance rate was lower in the high-dose group (t = -3.125, p = 0.002), and the improvement in SOFA score at 72 h was worse (t = 2.894, p = 0.004). Furthermore, the incidence of acute kidney injury (χ² = 4.012, p = 0.045) and the new-onset severe arrhythmias (χ² = 5.124, p = 0.024) were higher in the high-dose group.

Among patients with refractory shock supported by VA-ECMO, a higher norepinephrine-equivalent dose during the initial support period is independently associated with an increased risk of death and worse clinical outcomes. This suggests the need for careful evaluation and optimization of vasopressor intensity, even when ECMO provides circulatory support.