Vasopressors and Inotropes: Overview and Selection of Agents

Types of Shock and Use of Vasoactive Infusions

• Shock is a condition characterized by inadequate oxygen delivery to meet metabolic demands at the cellular and tissue levels.¹ Shock is initially reversible but becomes irreversible if left untreated. The consequences of unmet demands include circulatory instability, lactic acidosis, severe systemic hypotension, and multiple system organ dysfunction.
• There are different types of shock, which are categorized based on the etiology of circulatory failure. The various kinds of shock and effective vasoactive infusions are summarized in Table 1.²
  • Distributive: shock secondary to severe peripheral vasodilation, despite possible increased CO.
  • Cardiogenic: shock secondary to reduced CO from intracardiac dysfunction.
  • Hypovolemic: shock secondary to reduced CO from decreased intravascular volume.
  • Obstructive: shock secondary to reduced CO from extracardiac causes, limiting forward circulatory flow.
• Please see the OA summary “Shock: Overview and Classification.” Link

Vasopressors: Mechanism of Action

• When supporting a patient in shock with hemodynamic instability, three main categories of vasoactive agents can be used: pure vasopressors, mixed vasopressor and inotropes (often called inopressor), and pure inotropes.
  • Pure vasopressor: Predominantly increases vascular tone or systemic vascular resistance (SVR) without significant impact on cardiac contractility (examples: phenylephrine, vasopressin, angiotensin II)
  • Mixed vasopressor and inotrope: Increases SVR and cardiac contractility (examples: epinephrine, norepinephrine, dopamine)
  • Pure inotrope: Predominantly increased cardiac contractility (examples: milrinone, isoproterenol, dobutamine)
• Table 2 summarizes the mechanism of action and effects of vasopressors (pure and mixed inotropes).^1-3

• Vasopressors induce vasoconstriction, increasing the mean arterial pressure (MAP) by augmenting the SVR. MAP = (CO × SVR) + CVP, where CO is CO and CVP is central venous pressure. The mixed vasopressors and inotropes increase the MAP by increasing both the SVR and the CO.
• The vasopressors and mixed vasopressor inotropes most commonly used are phenylephrine, epinephrine, norepinephrine, dopamine, vasopressin, and angiotensin II.
  • Phenylephrine is an α-1 agonist that induces vasoconstriction, reflex bradycardia, and decreased CO.
  • Norepinephrine acts on α-1 and α-2 receptors more than β-1 and β-2 receptors, increasing MAP without decreasing CO.
  • Epinephrine exhibits dose-dependent activity on all adrenergic receptors, resulting in a more pronounced vasoconstriction with higher doses. Epinephrine acts on β receptors at a lower dose, and on α receptors at a higher dose.
  • Dopamine acts on dopaminergic and adrenergic receptors, increasing the SVR at higher doses.
  • Vasopressin produces vasoconstriction by acting on V1 receptors in the vascular smooth muscles. Vasopressin is used as the second line for septic shock.⁵
  • Angiotensin II produces vasoconstriction by stimulating AT1 receptors in the vascular smooth muscles.

Inotropes: Mechanism of Action

• Inotropes include both adrenergic and non-adrenergic agents. The inotropic adrenergic agents include epinephrine, dopamine, dobutamine, and isoproterenol. The non-adrenergic inotropic agents include milrinone, digoxin, and levosimendan.
  • Epinephrine is a mixed inotrope and vasopressor with affinity for both α and β receptors. Low dose of epinephrine acts on β receptors, while at high doses, it acts on α receptors.
  • Dopamine is a precursor of epinephrine and norepinephrine and acts in a dose-dependent fashion on dopaminergic receptors and α and β receptors. Dopamine acts on dopamine receptors at lower doses, β receptors at medium doses, and α receptors at higher doses.
  • Dobutamine is a synthetic adrenergic agent that acts on β-1 more than β-2 receptors.
  • Isoproterenol is a synthetic non-selective β-adrenergic receptor agonist used primarily for treating bradycardia.
  • Milrinone is a phosphodiesterase inhibitor that increases cyclic adenosine monophosphate (cAMP), which stimulates cardiomyocytes and enhances CO; it also has a vasodilatory effect in smooth muscles, decreasing SVR and PVR.
  • Digoxin is a Na+/K+ pump inhibitor that increases the intracellular calcium in cardiac myocytes, leading to increased contractility and decreased chronotropy.
  • Levosimendan increases the sensitivity of cardiac troponin C to calcium ions within cardiomyocytes, leading to enhanced contractility.
• Table 3 summarizes the mechanism of action and effects of commonly used inotropes.