Inotropes

• Inotropes are vasoactive medications that increase cardiac output.
• Inotropes are used to support cardiac function in low cardiac output states caused by decompensated heart failure, shock, surgery, or cardiac arrest.
• Many vasoactive agents have both vasopressor and inotropic actions; choice of agent primarily depends on the etiology of hemodynamic instability and goals of treatment.

Systemic blood pressure is determined by systemic vascular resistance (SVR) and cardiac output. Inotropes increase cardiac contractility and cardiac output via stimulation of beta₁-receptors in the heart.[65552] [65553]

Catecholamines mediate their cardiovascular actions predominately through 3 types of receptors: 1) alpha-adrenergic, 2) beta-adrenergic, and 3) dopaminergic. Dopamine displays dose-related receptor activity, targeting dopaminergic receptors at low doses, dopaminergic and beta-receptors at mid-range doses, and shifting to beta- and (preferentially) alpha-receptor stimulation at high doses. Dobutamine is a synthetic catecholamine with a strong affinity for both beta₁- and beta₂-receptors. Epinephrine is a potent nonselective alpha- and beta-agonist. Its beta effects predominate at lower doses, while alpha₁-mediated vasoconstriction predominates at high doses. Isoproterenol is a potent nonselective beta-agonist with a very low affinity for alpha-receptors.[54335] [65549] [65550]

Milrinone is a phosphodiesterase inhibitor (PDI) distinct from other inotropes. PDIs increase cyclic adenosine monophosphate (cAMP) by inhibiting breakdown within cardiac and vascular muscle cells, which leads to an increase in myocardial contractility.[30865] [54335]

Receptor Pharmacology of Catecholamines [54335] [65550] [65549] [65564]

*Dose listed for dose-related receptor activity only

Locations and Responses of Select Receptors [54335] [65549] [65550]

• Agents with both alpha- and beta- effects (e.g., dopamine, epinephrine) are used in cardiogenic shock to increase both mean arterial pressure (MAP) and cardiac output (CO).[65299][65553][65554] Mixed agents generally increase CO at lower doses, but may decrease CO at higher doses.[65553]
• Pure inotropes (e.g., dobutamine, milrinone) are used for treating heart failure or for postoperative CO support when MAP is adequate.[65299][65553]
• Inotropes are also used in distributive/vasodilatory shock once adequate perfusion pressure is established, to increase oxygen delivery.[65553]
• Dobutamine is recommended in hemodynamically stable patients with cardiogenic shock and low-output syndrome.[31689][65298][65299][65564] It is also recommended as an adjunct to norepinephrine in patients with septic shock and cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial blood pressure.[67037]
• Dobutamine is preferred over milrinone in patients who are acutely unstable, hypotensive, or those with renal insufficiency.[65564][65578][65583]
• Milrinone is preferred for patients with chronic heart failure, especially in the presence of significant right ventricular dysfunction, pulmonary hypertension, or concomitant beta-blocker therapy.[65564][65578][65583]
• Isoproterenol use is limited to patients refractory to other inotropic agents.[65552]

• Few clinical outcome data are available to guide initial selection of vasoactive agents in patients with cardiogenic shock.[65299]
• There was no significant difference in mortality when comparing dopamine and norepinephrine as first-line vasoactive agents in the treatment of shock (n = 1,679); however, dopamine was associated with a higher rate of arrhythmias, including arrhythmias severe enough to require discontinuation of the study drug. Among patients with cardiogenic shock (n = 280), mortality was significantly higher in the dopamine group.[43703]
• Both epinephrine and norepinephrine-dobutamine improved cardiac index, arterial pressure, and oxygen delivery in patients with cardiogenic shock (without acute coronary syndrome) after failure of dopamine (n = 30); however, epinephrine was associated with transient lactic acidosis, inadequate gastric mucosa perfusion, increased heart rate, and arrhythmia.[65585]
• Dobutamine and milrinone have similar clinical effects in patients with severe heart failure.
• Both dobutamine and milrinone were used successfully as a pharmacologic bridge to heart transplantation (n = 36) with no significant differences in right heart hemodynamics, need for additional vasodilator/inotropic therapy, need for mechanical cardiac support, or death.[65584]
• There was no difference in mortality between chronic dobutamine or milrinone in patients with stage D heart failure being discharged from the hospital (n = 112).[65583]