Dose-related systemic and cerebral hemodynamic effects of norepinephrine in newborn piglets with hypoxia-reoxygenation.

Abstract

Background: Little is known regarding systemic and regional hemodynamic effects of norepinephrine (NE) in hypotensive neonates after hypoxia-reoxygenation (H-R). We hypothesized that NE would improve cardiac function, systemic and cerebral hemodynamics without aggravating hyperlactatemia during H-R, compared with epinephrine (EPI).

Methods: In an established model of neonatal H-R, piglets were treated with either NE (0.05, 0.1 and 0.2 µg/kg/min), EPI (0.1 µg/kg/min) or saline for 2 h during reoxygenation in a blinded, randomized fashion (n = 8/group). Systemic hemodynamics, carotid blood flow, cerebral oxygenation, and cardiac contractile function were continuously measured. Myocardial, cerebral, renal and intestinal tissues were analyzed for lactate and oxidative stress levels.

Results: Norepinephrine (0.1 and 0.2 µg/kg/min) and EPI increased mean arterial pressure and cardiac output with corresponding changes in left ventricular systolic, but not diastolic, function. Norepinephrine at 0.1 µg/kg/min had the optimal systemic hemodynamic effects and cerebral perfusion with lower plasma lactate. Tissue lactate and oxidative stress levels were not different.

Conclusions: In newborn piglets with H-R, NE improved cardiac contractile function, cardiac output, blood pressure, and cerebral perfusion in a dose-related manner. Clinical studies of NE on systemic and regional hemodynamic effects in asphyxiated neonates are required to confirm the findings in this pre-clinical study.

Impact: In an established model of neonatal hypoxia-reoxygenation, 2-h infusion of norepinephrine at 0.05-0.2 µg/kg/min has dose-related increases in cardiac systolic contractile function and systemic blood pressure with corresponding improvements in cerebral perfusion in newborn piglets, without significant changes in ischemic and oxidative stress markers in tissues. The hemodynamic effects of norepinephrine are comparable to those of epinephrine which causes increased plasma lactate. While norepinephrine is an effective inotropic vasopressor in the treatment of hypotensive shock in neonates with hypoxia-reoxygenation, studies are required to confirm its effects and safety in prolonged administration in clinical trials.