Systemic pressure-flow reactivity to norepinephrine in rabbits: impact of endotoxin and fluid loading.

OBJECTIVE: This study aimed to evaluate the impact of fluid loading on hemodynamics and vascular hypocontractility to norepinephrine (NE) in an endotoxic shock model.

DESIGN: Mean arterial pressure (MAP), aortic blood flow velocity (AoV, 20 MHz Doppler) and aortic conductance (AoC = AoV/MAP) were studied during 180 min (T0-T180) in 41 anesthetized and ventilated rabbits.

INTERVENTIONS: Shock was induced by a 600 micrograms/kg bolus injection of endotoxin. Fluid loading (20 ml/kg colloids) was infused from T90 to T120. Dose-response curves to NE were performed at T0, T60 and T120 in endotoxic and non-endotoxic animals with or without fluid loading.

MEASUREMENTS AND RESULTS: Endotoxin decreased pressure (-23%, p < 0.05) and flow (-42%, p < 0.05) corresponding to a decrease in conductance (-19%, p < 0.05). Fluid loading did not improve hypotension but markedly increased systemic flow (+51%, p < 0.01), corresponding to a hyperkinetic syndrome. Vascular reactivity to NE was impaired after endotoxin at T60 since the pressure response to NE was depressed (p < 0.01) and flow did not decrease. In non-fluid-loaded groups, the pressure response to NE recovered at T120, with no reduction in flow. In fluid-loaded endotoxic animals, however, the pressure response to NE was still impaired at T120 (p < 0.05), but with a decrease in flow.

CONCLUSIONS: Fluid loading transformed the hypodynamic profile of endotoxic shock into a hyperdynamic state without improving blood pressure. Depressed vascular reactivity to NE was observed in both hyperdynamic and hypodynamic states, suggesting that a reduced vascular reactivity does not necessarily imply systemic vasodilation.