Abstract 2272: Comparing the Hemodynamic Effects of Milrinone, Epinephrine and Dobutamine in a Swine Model of Neonatal Asphyxia-Reoxygenation
Introduction: Hypotension, shock and decreased regional perfusion often develop after neonatal resuscitation. Clinically, epinephrine (E) and dobutamine (D) are used to treat these effects whereas milrinone (M) is mainly used for neonates with cardiac surgery. There is little comparative data on the hemodynamics and oxygen metabolism of these drugs in neonatal asphyxia-reoxygenation (AR).
Hypothesis: In a swine model of neonatal AR, E, D and M will
improve cardiac output (CI) and systemic oxygen delivery (DO2) with more vasopressive effects
by E and D. Due to its vasodilatory action, M but not E or D will decrease vascular resistance and increase regional flows.
Methods: Piglets (1–3d, 1.5–2.5kg) were acutely instrumented to measure MAP, PAP, blood flows in the left common carotid, superior mesenteric, left renal and main pulmonary arteries (CAFI, SMAFI, RAFI and CI, respectively). Ductus Arteriosus was ligated. Normocapnic hypoxia (FiO2=0.08 – 0.15) was induced for 2h followed by reoxygenation with 100%O2 (1h) then 21%O2 (3h). At 2h of reoxygenation, saline, E (0.5μg/kg/min), D (20μg/kg/min) or M (0.75μg/kg/min) infusions were given for 2h in a blinded randomized manner (n=6/group). The dosages were chosen based on the hemodynamic efficacy in this model. Hemodynamic and oxygen transport data were studied at pre-defined timepoints.
Results: Hypoxia (PaO2 34±[SEM]1mmHg; pH 7.03±0.02) reduced CI (38±1% baseline) and regional flows. Hemodynamic parameters recovered with reoxygenation but then deteriorated over 2h (MAP:58±2%; CI:68±2%; CAFI:70±4%; SMAFI:83±4%; RAFI:71±4%). E, D or M infusion increased CI and systemic DO2 (p<0.05, ANOVA). MAP was maintained with D and M (p<0.05 vs. control) and increased by E (p<0.05 vs. all groups). PAP did not differ between groups and pulmonary vascular resistance was lower in E, D and M (vs.control). While E, D and M increased CAFI, SMAFI and the respective DO2, M also lowered the vascular resistance (p<0.05) with improved renal perfusion (p<0.06).
Conclusions: In newborn pigs with AR, E, D and M have similar inotropic actions. E increases while D and M maintain MAP. M increases regional perfusion better than E and D. Clinical trials comparing M to standard therapies for hemodynamic dysfunction in neonatal AR are warranted.