Milrinone, dobutamine or epinephrine use in asphyxiated newborn pigs resuscitated with 100% oxygen.
BACKGROUND
After resuscitation, asphyxiated neonates often develop poor cardiac function with hypotension, pulmonary hypertension and multiorgan ischemia. In a swine model of neonatal hypoxia-reoxygenation, effects of epinephrine, dobutamine and milrinone on systemic, pulmonary and regional hemodynamics and oxygen transport were compared.


METHODS
Controlled, block-randomized study.


METHODS
University research laboratory.


METHODS
Mixed breed piglets (1-3 days, 1.5-2.3 kg).


METHODS
In acutely instrumented piglets, normocapnic alveolar hypoxia (10-15% oxygen) was induced for 2 h followed by reoxygenation with 100% oxygen (1 h) then 21% oxygen (3 h). At 2 h of reoxygenation, after volume loading (Ringer's lactate 10 ml/kg), either saline (placebo), epinephrine (0.5 microg/kg/min), dobutamine (20 microg/kg/min) or milrinone (0.75 microg/kg/min) were infused for 2 h in a blinded, block-randomized fashion (n = 6/group).


RESULTS
All medications similarly improved cardiac output, stroke volume and systemic oxygen delivery (vs. placebo-controls, p < 0.05). Epinephrine and dobutamine significantly increased, while milrinone maintained, mean arterial pressure over pretreatment values while placebo-treated piglets developed hypotension and shock. The mean arterial to pulmonary arterial pressures ratio was not different among groups. All medications significantly increased carotid and intestinal, but not renal, arterial blood flows and oxygen delivery, whereas milrinone caused lower renal vascular resistance than epinephrine and dobutamine-treated groups. Plasma troponin I, plasma and myocardial lactate levels, and histologic ischemic features were not different among groups.


CONCLUSIONS
In newborn piglets with hypoxia-reoxygenation, epinephrine, dobutamine and milrinone are effective inotropes to improve cardiac output, carotid and intestinal perfusion, without aggravating pulmonary hypertension. Milrinone may also improve renal perfusion.
Joynt
Chloë
C
Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
Bigam
David L
DL
Charrois
Gregory
G
Jewell
Laurence D
LD
Korbutt
Gregory
G
Cheung
Po-Yin
PY
D000818:Animals; D000831:Animals, Newborn; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004280:Dobutamine / Q000008:administration & dosage / Q000494:pharmacology*; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D000860:Hypoxia; D008297:Male; D020105:Milrinone / Q000008:administration & dosage / Q000494:pharmacology*; D010100:Oxygen / Q000008:administration & dosage*; D011897:Random Allocation; D012151:Resuscitation / Q000379:methods*; D013552:Swine
D001993:Bronchodilator Agents; D002316:Cardiotonic Agents; D004280:Dobutamine; D020105:Milrinone; D010100:Oxygen; D004837:Epinephrine