Chapter 30: Vasoactive Agents

INTRODUCTION

Vasoactive medications and inotropic agents are utilized frequently in the pediatric intensive care unit for patients in various states of shock. Selecting the proper pharmacologic therapy requires knowledge of the mechanism of action of each medication, as well as the etiology of the patient's physiologic derangement.

RECEPTOR CLASSES (SEE TABLE 30-1)

TERMINOLOGY

SYMPATHOMIMETIC AGENTS

• Dopamine

  • Dopamine is the precursor to epinephrine and norepinephrine. It has cardiac and vascular effects that are dose dependent.¹

    • At moderate doses (4–10 mcg/kg/min), it acts as a weak partial agonist at myocardial β₁-receptors, resulting in positive inotropy.

      • Additionally, it causes the release of norepinephrine from sympathetic nerve terminals in the myocardium and vasculature, which may lead to vasoconstriction.

    • At high doses (10–20 mcg/kg/min), it stimulates α receptors, resulting in vasoconstriction.

• Epinephrine

  • Epinephrine is an endogenous catecholamine. It has potent cardiac and vascular effects.

    • It stimulates β₁- and β₂-receptors in the myocardium, resulting in positive chronotropic and inotropic responses.

      • Higher doses of epinephrine may lead to tachycardia, increased risk of arrhythmia, and increased myocardial oxygen consumption.

    • It also has effects on α receptors, resulting in increased arterial and venous constriction.

• Norepinephrine

  • Norepinephrine is an endogenous catecholamine. It has potent vascular and some cardiac effects.

    • It primarily stimulates α receptors, resulting in vasoconstriction.

    • It has a weak effect on β₁-receptors in the myocardium.

• Isoproterenol

  • Isoproterenol is a synthetic sympathomimetic with a molecular structure that is similar to epinephrine.

    • It acts as a nonselective β-receptor agonist with limited to no alpha effects.

      • Stimulation of β₁- and β₂-receptors in the myocardium results in positive chronotropic and inotropic responses.

      • Stimulation of β₂-receptors in the vasculature results in pulmonary and skeletal muscle vasodilation, which may result in hypotension.

• Phenylephrine

  • Phenylephrine is a synthetic sympathomimetic

    • It is a selective alpha-1-adrenergic receptor agonist, resulting in vasoconstriction

    • Reflex bradycardia may occur

NONSYMPATHOMIMETIC AGENTS

• Milrinone:

  • Milrinone is a phosphodiesterase-3 inhibitor.

    • Inhibition results in improved Ca²⁺ release and increased myocardial contraction.²

    • It is a positive inotrope, lusitrope, and vasodilator.

    • Vasodilation results in decreased afterload.

  • Does not increase intrinsic myocardial oxygen consumption.

  • Dosing adjustment is required in renal failure.

    • Drug accumulation in cases of renal failure may occur, resulting in hypotension.

• Vasopressin:

  • Vasopressin is ...