Norepinephrine Equivalent Dose for Mortality Risk Stratification in VA-ECMO Cardiogenic Shock

Patients with cardiogenic shock (CS) complicated by vasoplegia requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO) often need escalating vasopressor support and face high mortality. Norepinephrine equivalent dose (NEE) quantifies vasopressor burden, yet its prognostic value in VA-ECMO remains undefined.

We aimed to characterize the dose-response relationship between NEE and 30-day mortality, identify a clinically relevant NEE threshold, and determine factors associated with high vasopressor burden.

This bicentric retrospective study included 572 consecutive patients with CS requiring VA-ECMO. We collected vasopressor regimens, NEE trajectories, and hemodynamic parameters at predefined intervals. Restricted cubic splines assessed dose-response linearity. Maximally selected rank statistics with bootstrap validation identified optimal thresholds. Cox models estimated mortality risk. Multivariable logistic regression identified factors associated with high vasopressor burden.

The median NEE at ECMO initiation was 0.30 (IQR: 0.09-0.72) μg·kg^-1·min^-1; 86.2% received norepinephrine. NEE showed a linear dose-response with mortality (HR: 1.06 per 0.1 μg·kg^-1·min^-1 increment; 95% CI: 1.04-1.08; P < 0.001). A threshold of 0.443 μg·kg^-1·min^-1 identified high vasopressor burden with elevated 30-day mortality (61.8% vs 42.6%; P < 0.001; adjusted HR: 1.42; 95% CI: 1.11-1.81; P = 0.005). Factors associated with high vasopressor burden included mechanical ventilation (OR: 2.96; 95% CI: 1.08-8.07), prior epinephrine use (OR: 1.87; 95% CI: 1.12-3.14), renal replacement therapy before VA-ECMO (OR: 1.76; 95% CI: 1.02-3.03), baseline lactate (OR: 1.05 per mmol/L; 95% CI: 1.01-1.09), and lower Survival After Veno-Arterial ECMO score (OR: 0.96 per point; 95% CI: 0.92-1.00). Left ventricular unloading was inversely associated (OR: 0.54; 95% CI: 0.34-0.87).

In VA-ECMO-supported CS with vasoplegia, vasopressor burden shows a linear relationship with mortality. A NEE threshold of 0.443 μg·kg^-1·min^-1 may identify patients with elevated mortality risk.