Adrenergic Drugs Alter Both the Fluid Kinetics and the Hemodynamic Responses to Volume Expansion in Sheep

Background

Plasma volume expansion is often performed during adrenergic therapy in the intensive care unit, but little is known about their combined effects.

Materials and methods

The influence of three adrenergic drugs (50 μg/kg/min of dopamine, 0.1 μg/kg/min of isoprenaline, or 3 μg/kg/min of phenylephrine) on the relationship between plasma dilution (an index of volume expansion) and the central hemodynamic responses to volume loading with 24 ml/kg of 0.9% saline were evaluated in 6 adult sheep. Kinetic analysis was also applied to the data on plasma dilution and the urinary excretion measured during and after volume loading.

Results

The adrenergic agents markedly changed the baseline values for all hemodynamic parameters. The kinetic analysis showed that phenylephrine, which is an alpha-adrenergic receptor agonist, promoted renal excretion of infused fluid at the expense of fluid distribution to the periphery (P < 0.05 versus controls). Isoprenaline, which stimulates adrenergic beta-receptors, had the opposite effect. During volume expansion, cardiac atrial pressures increased by 25 to 90%, cardiac output by 13–80% and the arterial pressures by 2 to 22%. Plasma dilution during and after volume loading correlated, in a linear fashion, with these hemodynamic responses. The correlations were strong (r > 0.80) in the control and phenylephrine groups, but weaker in the dopamine and isoprenaline groups. Dopamine was associated with the most variable hemodynamic responses overall.

Conclusions

Adrenergic drugs altered the hemodynamics at baseline (direct effects), changed the distribution and elimination of infused 0.9% saline (indirect effects) and, finally, modified most hemodynamic responses to plasma dilution (interaction effects).

Introduction

Infusions of crystalloid fluid and adrenergic drugs are common treatments during intensive care. How volume loading augments the cardiovascular system is well known, and the hemodynamics may even be used to indicate the patient’s volume status [1, 2]. The cardiovascular responses to volume loading in the presence of adrenergic therapy are more unclear, although several types of influences are possible. Adrenergic drugs exert direct stimulation of adrenergic receptors in cardiovascular tissue. The effects could also be indirect via a change of the distribution and elimination of the infused fluid. The direct effects can be modified by changing the dose of the drug, while the indirect ones require that the rate of infusion of the crystalloid fluid is altered. Finally, one might consider the possible existence of combined or interaction effects between adrenergic receptor stimulation and plasma volume expansion. Such interactions would imply that the hemodynamic responses to plasma volume expansion differ depending on the type of adrenergic receptor that is stimulated.

The purpose of this presentation was to separate the direct, indirect and interaction effects based on experiments in sheep in which they received a rapid infusion of 0.9% saline alone and during concomitant administration of three adrenergic drugs (dopamine, isoprenaline, or phenylephrine). Plasma dilution was used as the measure of intravascular volume expansion and served as a link between fluid therapy and hemodynamic response. Plasma dilution and the urinary excretion were also used as input variables for kinetic calculations to outline the disposition of 0.9% saline [3, 4, 5].

The drugs were selected to contrast activation of different adrenergic receptors. Isoprenaline is a beta-receptor agonist and phenylephrine an alpha-adrenergic receptor agonist. Low doses of dopamine stimulate dopamine receptors, intermediate doses beta-adrenergic receptors, and high doses also alpha-receptors [6, 7]. The present evaluation is an in-depth extension of a general presentation of the influence of these drugs on the blood volume [8].