A comparison of combination dopamine and epinephrine treatment with high-dose dopamine alone in asphyxiated newborn piglets after resuscitation

Abstract

Background: When asphyxiated neonates require additional cardiovascular support to moderate doses of dopamine infusion, controversy exists on the differential hemodynamic effects of two approaches (adding a second inotrope vs. increasing dopamine dosage). We hypothesized that high-dose dopamine (HD) would be detrimental to systemic and regional perfusion as compared with dopamine and epinephrine (D + E) combination therapy using a swine model of neonatal hypoxia-reoxygenation (H-R).

Methods: Twenty-seven piglets (1-4 d, 1.5-2.5 kg) were used for continuous monitoring of systemic arterial pressure (mean arterial pressure, MAP) and pulmonary arterial pressure (PAP), cardiac output (cardiac index, CI), and carotid (carotid artery flow index, CAFI), superior mesenteric (superior mesenteric artery flow index), and renal arterial flows. H-R piglets underwent 2 h of hypoxia followed by 2 h of reoxygenation before drug infusion (2 h).

Results: The hemodynamics of H-R piglets deteriorated gradually after reoxygenation. HD and D + E infusions improved CI similarly (both groups vs. control; P < 0.05). Both regimens increased MAP (P < 0.05) but not PAP, with decreased PAP/MAP ratio in D + E piglets. Both regimens improved CAFI and superior mesenteric artery flow index, with decreased mesenteric vascular resistance in HD-treated piglets. No significant effect on renal perfusion was observed.

Conclusion: In H-R newborn piglets treated with a moderate dose of dopamine, adding epinephrine or further increasing dopamine improved systemic hemodynamics similarly; these treatments have differential effects on the pulmonary and mesenteric circulations.

Figure 1

Changes in (A) heart rate (HR), (B) stroke volume index (SVI) and (C) cardiac index (CI) during the 2h infusion of combination dopamine and epinephrine (grey) and high-dose dopamine (black) in H-R piglets in comparison with controls (white) (n=7/group). Stroke volume index and cardiac index are expressed as mean percentage change over duration of infusion from pre-drug baseline. * p<0.05 vs. control (2-way repeated measures ANOVA).

Figure 2

Changes in (A) mean arterial pressure (MAP), (B) pulmonary artery pressure (PAP) and (C) PAP/MAP ratio during the 2h infusion of combination dopamine and epinephrine (grey) and high-dose dopamine (black) in H-R piglets in comparison with controls (white) (n=7/group). PAP/MAP ratio is expressed as mean percentage change over duration of infusion from pre-drug baseline. * p<0.05 vs. control (2-way repeated measures ANOVA).

Figure 3

Changes in (A) carotid, superior mesenteric (SMA) and renal arterial flows and (B) respective vascular resistance during the 2h infusion of combination dopamine and epinephrine (grey) and high-dose dopamine (black) in H-R piglets in comparison with controls (white) (n=7/group). Data are expressed as mean percentage change over duration of infusion from pre-drug baseline. * p<0.05 and † p=0.05 vs. control; ‡ p=0.07 vs. combination dopamine and epinephrine group (2-way repeated measures ANOVA).

Figure 4

Changes in (A) systemic (SYS) oxygen delivery (DO₂) and consumption (VO₂) and (B) carotid, superior mesenteric and renal DO₂ during the 2h infusion of combination dopamine and epinephrine (grey) and high-dose dopamine (black) in H-R piglets in comparison with controls (white) (n=7/group). Data are expressed as mean percentage change over duration of infusion from pre-drug baseline. * p<0.05 and † p<0.1 vs. control (2-way repeated measures ANOVA).

Figure 5

Experimental protocol.