Effect of increasing norepinephrine dosage on regional blood flow in a porcine model of endotoxin shock.

Objective: To evaluate the effect of a norepinephrine-induced differential increase in mean arterial pressure on splanchnic and renal perfusion in a porcine model of volume-resuscitated endotoxic shock.

Design: Prospective, controlled, acute interventional study.

Setting: Animal research laboratory.

Subjects: Fourteen landrace pigs, seven treated with norepinephrine and seven used as endotoxemic controls.

Interventions: In an acute endotoxic shock model, norepinephrine was used to reverse hypotension in seven fluid-resuscitated pigs, anesthetized with alpha-chloralose and equipped with flow probes around the portal vein and renal artery, renal and jejunal mucosal laser Doppler flowmetry, and jejunal tonometry. Mean arterial pressure was increased by 10 and then 20 mm Hg above the shock level with norepinephrine. Seven shocked, fluid-resuscitated only animals served as the comparison group.

Measurements And Main Results: Measurements were performed before 2-hr endotoxin infusion and at the end of each increased level of mean arterial pressure. Raising mean arterial pressure with norepinephrine by 10 mm Hg significantly increased cardiac output, systemic oxygen extraction, and portal vein blood flow; stabilized metabolic acidosis; and tended to restore renal and jejunal mucosal flows to preshock levels. Increasing mean arterial pressure by 20 mm Hg further increased cardiac output and oxygen delivery but without improving portal vein, renal artery, and jejunal mucosal blood flows.

Conclusions: Norepinephrine, administered to increase mean arterial pressure by 10 mm Hg in an acute model of volume-resuscitated endotoxic shock, improved systemic and regional perfusion. The administration of norepinephrine to increase mean arterial pressure 20 mm Hg above shock did not increase renal and splanchnic blood flows, despite an enhanced cardiac output.