The effects of dopamine and epinephrine on hemodynamics and oxygen metabolism in hypoxic anesthetized piglets

Abstract

The most appropriate inotropic agent for use in the newborn is uncertain. Dopamine and epinephrine are commonly used, but have unknown effects during hypoxia and pulmonary hypertension; the effects on the splanchnic circulation, in particular, are unclear. respectively were infused for 1 h at each dose. Results were compared with the 1 h hypoxia values by two-way analysis of variance. ; dopamine had no effect on hepatic arterial flow at any dose. Despite these hemodynamic changes, there were no differences in systemic or splanchnic oxygen extraction or consumption at any dose of dopamine or epinephrine. Epinephrine is more effective than dopamine at increasing cardiac output during hypoxia in this model. Although epinephrine preserves the SAP/PAP ratio, dopamine shows preferential pulmonary vasoconstriction, which might be detrimental if it also occurs during the management of infants with persistent fetal circulation. Dopamine, but not epinephrine, increases portal flow and total hepatic flow during hypoxia.

Background:

The most appropriate inotropic agent for use in the newborn is uncertain. Dopamine and epinephrine are commonly used, but have unknown effects during hypoxia and pulmonary hypertension; the effects on the splanchnic circulation, in particular, are unclear.

Methods:

respectively were infused for 1 h at each dose. Results were compared with the 1 h hypoxia values by two-way analysis of variance.

Results:

; dopamine had no effect on hepatic arterial flow at any dose. Despite these hemodynamic changes, there were no differences in systemic or splanchnic oxygen extraction or consumption at any dose of dopamine or epinephrine.

Conclusions:

Epinephrine is more effective than dopamine at increasing cardiac output during hypoxia in this model. Although epinephrine preserves the SAP/PAP ratio, dopamine shows preferential pulmonary vasoconstriction, which might be detrimental if it also occurs during the management of infants with persistent fetal circulation. Dopamine, but not epinephrine, increases portal flow and total hepatic flow during hypoxia.

Introduction

], it is uncertain whether these agents are appropriate in the treatment of shock or hypotension in sick newborns who are at risk for the development of persistent fetal circulation and necrotizing enterocolitis. Indeed, the appropriate catecholamine in various clinical situations also remains undetermined for the critically ill adult.

), produced a pulmonary vasodilatation; in comparison, dopamine had no such effect. However, there are no data on the effects on mesenteric hemodynamics and oxygen metabolism of infusions of either dopamine or epinephrine during hypoxia.

The objectives of this study were to evaluate the effects of dopamine and epinephrine infusions in hypoxic piglets on systemic, pulmonary, and mesenteric circulations, and on systemic and splanchnic oxygen metabolism.

Statistical analysis

< 0.05 was considered significant. All results are expressed as means ± SD.

= 5)

significantly. Hepatic DO2 ratio was not affected. The control animals had no significant change in any of the recorded hemodynamic and metabolic variables over the subsequent 3 h of the study in comparison with the 1 h values. At 1 h of hypoxia the control group values for the above variables were not significantly different from the hypoxia baseline values in the other two groups.

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dopamine at the final 30 min were significantly different from these variables at the 1 h baseline and at all doses of the epinephrine group.

The decrease in mesenteric vascular resistance and the increase in hepatic venous flow during the highest dose of dopamine, with a stable CI, led to an increase in the total hepatic blood flow as a proportion of cardiac output.

increased significantly from the 1 h baseline. Serum lactate concentration was elevated by hypoxia but was not significantly affected by dopamine.

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, was significantly higher than that produced by any dose of dopamine.

There was no change in mesenteric vascular resistance and increase in CI with epinephrine; there was therefore a trend to a decrease in the total hepatic blood flow when expressed as a proportion of cardiac output, which was not statistically significant.

).

Discussion

Both dopamine and epinephrine are commonly used medications in the treatment of shock and hypotension in sick newborns. Our study is the first that compares the effects of dopamine and epinephrine infusions on regional hemodynamics and oxygen metabolism in a newborn mammal. It is also important to realize that all previous studies of the effects of inotropes in the newborn have used infusions for a maximum of 15-20 min. The prolonged inotrope infusions in our experiment are unique and are somewhat more relevant to the problem of cardiovascular support for the critically ill newborn, who might receive these drugs for hours or days.

Similarly, many newborns receiving these drugs are hypoxic, receive large doses of opiates to reduce instability, are critically ill and stressed, and might have recently had major surgery. Thus, although acutely instrumented models are often criticized for being 'unphysiologic,' the stress of surgery might, in some ways, represent the clinical situation in which these drugs are actually used more accurately than healthy, chronically instrumented, models. Nevertheless, the animal model employed in the present study does not completely mirror the conditions in critically ill newborn humans. Although sick hypoxic newborns are usually hypotensive as well, it is also important to realize that the animals had no underlying disease condition; some such conditions, for example sepsis, might modify responses to infused catecholamines. Because of potential differences in drug metabolism, the number, affinity, and maturation of adrenergic receptors, and cardiovascular reflexes, the responses described to any inotropic agent in a non-human mammal should be taken as only a guide to potential effects, which must be confirmed in human newborns.

]; the apparent carboxyhemoglobin levels in our piglets were almost always less than 2%, suggesting that the oxygen saturation values should be reliable. Furthermore, the trends shown are likely to be accurate, even if the actual values are somewhat imprecise.

].

].

]. It could therefore be that the dopamine infusion in O'Laughlin's study was begun at a time when the cardiac output was still increasing. The doses also seem to have been given in sequential rather than random order, which can lead to apparent effects that are due to the order of administration rather than a true dosage effect. O'Laughlin also reported drug effects after 15 min; we did not measure hemodynamics at this time, so we might have missed transient effects of the drugs.

].

stimulation. Thus the differences in both the epinephrine and dopamine responses during hypoxia would be explained by a reduction in α-mediated vasoconstriction.

].

-vasodilatation effect with epinephrine at low dose during hypoxia (as also reflected in the decrease in calculated SVRI); a low dose of epinephrine could also be protective and improve hepatic perfusion and oxygen delivery in hypoxic newborns. Further studies on hepatic perfusion and oxygen metabolism in systemic hypoxia are required for an evaluation of the hepatoprotective role of inotropes.

was demonstrated. We did not confirm this in our study, which might be related to the difference in oxygen metabolism in isolated hypoxia as opposed to hypoxia and sepsis, and to the duration of hypoxia between studies.

Conclusion

During severe alveolar hypoxia in the newborn piglet, epinephrine increases cardiac output whereas dopamine has no effect. Epinephrine preserves the SAP/PAP ratio, whereas dopamine causes pulmonary vasoconstriction. Epinephrine has no effect on splanchnic blood flow, whereas dopamine increases both portal and total hepatic flow. A reconsideration of the approach to the sick newborn infant is warranted.

Abbreviations

= oxygen consumption; THFI = total hepatic flow index.

Acknowledgement

This study was supported by the Heart and Stroke Foundation of Canada and Perinatal Research Centre, University of Alberta, Edmonton, Canada.

Figures and Tables

< 0.05 compared with effects of hypoxia.

< 0.05 compared with effects of hypoxia.

< 0.05 compared with effects of hypoxia.

< 0.05 compared with effects of hypoxia.

< 0.05 compared with effects of hypoxia.

< 0.05 compared with effects of hypoxia.

Effects (means ± SD) of prolonged hypoxia in five anesthetized control piglets

< 0.05 compared with normoxic baseline.

Effects (means ± SD) of dopamine infusions in six anesthetized hypoxic piglets

accounted for by hepatic arterial oxygen delivery; (HAFI + PVFI)/CI, total hepatic blood flow as a proportion of the cardiac index.

Effects (means ± SD) of epinephrine infusions in six anesthetized hypoxic piglets

that is accounted for by hepatic arterial oxygen delivery; (HAFI + PVFI)/CI, total hepatic Blood flow as a proportion of the cardiac index.

Keywords

• inotropes
• regional flow
• oxygen extraction
• piglets