Abstract
Left ventricular-arterial (V-A) coupling is a key determinant of cardiovascular performance, which integrates intrinsic myocardial contractility with ventricular afterload. Septic shock frequently disrupts this coupling, and norepinephrine (NE) may worsen it in some scenarios. In this study, we aimed to quantify the dose-response relationship between NE and V-A coupling and to test for interactions between NE and elapsed treatment time or cumulative infusion volume (IV) in patients with septic shock. In this single-center prospective cohort study, NE dose, hemodynamic indicators, IV, and pulse indicator continuous cardiac output (PiCCO) related parameters were collected every 3 h for 3-24 h and every 6 h for 24-48 h. The V-A coupling index was computed as the ratio of arterial elastance (Ea) to ventricular end-systolic elastance (Ees). Linear mixed effects models were used to estimate the effects of NE dose on Ea/Ees: Model 1 included NE dose, time, and interaction between NE and time (NE×Time); Model 2 added sex, age, body mass index, central venous pressure (CVP), IV, NE×Time, and NE×IV. The NE dose correlated positively with Ea/Ees. NE×Time was non-significant, indicating that the relationship between NE and Ea/Ees did not change over time. Each 1000 mL increase in IV decreased the Ea/Ees by 0.360; NE × IV showed no significance. High-dose NE exacerbated V-A decoupling without a time-dependent change. Cumulative IV modestly mitigated uncoupling, whereas the interaction between NE and IV was non-significant.