Milrinone, dobutamine or epinephrine use in asphyxiated newborn pigs resuscitated with 100% oxygen.
ABSTRACT 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.
Controlled, block-randomized study.
University research laboratory.
Mixed breed piglets (1-3 days, 1.5-2.3 kg).
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).
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.
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.
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ABSTRACT: Perinatal asphyxia can lead to multi-organ insult which includes cardiovascular dysfunction. The objective was to study the relationship between cardiac function, perfusion and troponin. Unit database was accessed to identify infants with perinatal asphyxia over the last 2 years. Information from medical records and archived echocardiographic images was retrieved. Comparisons for echocardiographic information were made with healthy term infants. Seventeen infants with perinatal asphyxia were identified, of which three were excluded (one-33 weeks gestation, two-coagulopathy and pulmonary hypertension); 14 infants received therapeutic hypothermia. Median (range) gestation and birthweight were 39 (37-42) weeks and 3,550 (2,380-3,992) g respectively. Mean (S.D.) rectal temperature and time of echocardiogram were 33.5 ± 0.5 °C and median (range) 7.7 h [3-10] respectively. Majority of infants had low biventricular outputs. Median (range) SVC flow was 29.8 ml/kg/min (13-96.2). Median (range) troponin was 0.77 μg/L (0.17-2.6); normal ≤ 0.08 μg/L. Markedly low coronary flows (diastolic VTI median (range) 2.1 (1.3-2.9) cm were noted compared to controls. Coronary flow had a significantly positive correlation with left ventricular output. Higher troponin levels were associated with lower aortic stroke velocity. A close association between cardiac output, perfusion and troponin was noted. A dichotomy between blood pressure and flow parameters was noted, indicating the wide variation in vascular resistance in these infants. Biventricular output, coronary and SVC flows were significantly higher in the control population. In conclusion, inter-variable relationship between cardiac output, coronary flow and troponin is an important addition to the understanding of cardiovascular impact of perinatal asphyxia.European Journal of Pediatrics 06/2012; 171(10):1511-7. · 1.91 Impact Factor
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ABSTRACT: Dopamine is commonly used for blood pressure support in the neonate, but has limited empirical evidence to support its use. We tested the hypothesis that after near-terminal asphyxia in utero, dopamine infusions would prevent secondary hypotension. Fetal sheep (122-129 days of gestation, term is 147 days) received umbilical cord occlusion for 15 min or sham occlusion (n=5). If MAP fell below 90% of baseline within 6 h after occlusion fetuses were randomized to either dopamine infusion starting at 4 μg/kg/min and titrated according to MAP up to a maximum of 40 μg/kg/min (n=5) or to the same volume of normal saline (n=5). Dopamine infusion, initiated at a median of 180 min (range 96-280), was associated with a marked, but transient increase in MAP and fall in femoral blood flow compared to saline. Terminal hypotension developed later in the 4/5 fetuses who received maximum dopamine infusions than in 5/5 receiving saline infusion (517 min (240-715) vs 106 min (23-497) after the start of infusions, p<0.05). In conclusion dopamine infusion delayed but did not prevent terminal hypotension after severe asphyxia.Experimental physiology 10/2012; · 3.17 Impact Factor
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ABSTRACT: There is little information regarding the comparative hemodynamic effects of adding milrinone or levosimendan to dopamine infusion in hypoxia-reoxygenated (H-R) newborns. Severely hypoxic piglets had cardiogenic shock with depressed cardiac index (CI) and mean arterial pressure (MAP). The hemodynamics deteriorated gradually after initial recovery upon reoxygenation. Heart rate and CI improved with milrinone (D+M) and levosimendan (D+L) administration (P < 0.05 vs. control). Both regimens improved carotid arterial flow and carotid vascular resistance; D+M additionally improved superior mesentric arterial flow (all P < 0.05 vs. control). No effect was found on renal arterial flow or elevated lactate state with either regimen. D+M piglets also had a lower myocardial oxidized/reduced glutathione ratio (P < 0.05 vs. control). In conclusion, adding milrinone or levosimendan to dopamine similarly improved systemic hemodynamics in H-R newborn piglets. Milrinone also improved mesenteric perfusion and attenuated myocardial oxidative stress. Twenty-eight piglets (1-4 d, 1.5-2.5 kg) were instrumented for continuous monitoring of systemic MAP and pulmonary arterial pressure (PAP), CI, and carotid, superior mesenteric, and renal arterial flows. Piglets were randomized with blinding to sham-operated, H-R control (saline), and H-R dopamine (10 μg/kg/min) with D+M or D+L groups. H-R piglets underwent H-R followed by 2 h of drug infusion after reoxygenation. Tissue was collected for biochemical/oxidative stress testing and histological analysis.Pediatric Research 03/2012; 71(3):241-6. · 2.67 Impact Factor