Inotropes and Vasopressors: Doses, indications, contraindications and effects

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Inotropes and vasopressors

Vasopressors induce vasoconstriction and increase mean arterial pressure (MAP). Inotropes increase cardiac contractile force (contractility). Several endogenous and synthetic agents exist and are frequently combined to achieve the desired hemodynamic outcome. Most agents exhibit both vasopressor and inotropic effects (Figure 1). Below follows a drug manual for use in the CCU (coronary care unit), ICU (intensive care unit) or ER (emergency room). Careful electrocardiographic and hemodynamic monitoring with ECG, central vein catheter and intra-arterial catheter (A-line) is warranted.

Chapter content

Overview of vasopressors and inotropes

Table 1. Drug manual for inotropes and vasopressors

Drug	Indications	Dose	α1 effect	β1 effect	β2 effect	D1/D2 effect	Result	Side Effects
Dopamine – low dose	Rarely used	Low dose: 0.5-3.0 μg/kg/min	+	+	+	+++++	Low dose dopamine stimulates D1 receptors and induces vasodilation in coronary, renal, cerebral and mesenteric vessels.	Few
Dopamine – medium dose	Cardiogenic shock Vasodilatory shock Heart failure (HF), acute Heart failure (HF), chronic Bradycardia (second-line alternative)	Medium dose: 3.0-10.0 μg/kg/min.	+	++++	+	+++++	Medium dose dopamine activates β1, releases norepinephrine and thus increases contractility, chronotropy and mild increase in SVR.	Ventricular arrhythmias Myocardial ischemia Tissue ischemia (high doses or extravasation)
Dopamine – high dose	Cardiogenic shock Vasodilatory shock Heart failure (HF), acute Heart failure (HF), chronic Bradycardia (second-line alternative)	High dose: 10.0-20.0 μg/kg/min.	++++	++++	++	+++++	Hig dose dopamine additionally induces α1 stimulation and thus vasoconstruction and pronounced increase in SVR.	As medium dose, and additionally severe hypertension (caution if patient on nonselective beta-blockers).
Dobutamine	Cardiogenic shock Bradycardia (second-line therapy) Stress testing (due to induced increase in myocardial O₂ consumption)	Regular: 2.0–20 μg/kg/min Max: 40 μg/kg/min	+	+++++	+++	0	Potent inotrope with slight chronotropic effect. Doses <5 μg/kg/min induces mild vasodailation. Doses >5 μg/kg/min induces vasoconstriction, which dominates at dosease >15 μg/kg/min.	Tachycardia Increased ventricular rate in AF Ventricular arrhythmias Cardiac ischemia Hypertension (in patients on nonselective β-blocker) Tolerance after a few days
Norepinephrine	Shock (any) Hypotension (any)	0.01–3.0 μg/kg/min Safe for peripheral use	+++++	+++	++	0	Potent vasoconstrictor with mild inotropic effect. Increases systolic pressure, diastolic pressure and pulse pressure with minimal effect on CO. Minimal chronotropic effect. Increases coronary blood flow.	Atrial or ventricular arrhythmias Bradycardia Peripheral (digital) ischemia Hypertension (especially nonselective β-blocker patients) Prolonged use may be cardiotoxic.
Epinephrine	Shock (any) Cardiac arrest Bronchospasm Anaphylaxis Bradycardia (second-line alternative)	Infusion: 0.01 to 0.10 μg/kg/min Bolus: 1 mg IV every 3 to 5 min (max 0.2 mg/kg) IM: (1:1000): 0.1 to 0.5 mg (max 1 mg) Safe for peripheral use	+++++	++++	+++	N/A	Beta-effect more pronounced at low doses. Alpha-effect pronounced at higher doses. Coronary flow enhanced. Pulm vasoconstriction. Increased pulmonary blood flow.	Ventricular arrhythmias Severe hypertension resulting in cerebrovascular hemorrhage Cardiac ischemia Sudden cardiac death Prolonged use may be cardiotoxic.
Isoproterenol	Bradycardia (first-line therapy) Bradycardia causing torsade de pointes Brugada syndrome	2.0–10.0 μg/min Safe for peripheral use	0	+++++	+++++	0	Powerful chronotropic and inotropic effect. Potent systemic vasodilation. Mild pulmonary vasodilation. No effect on CO.	Ventricular arrhythmias Cardiac ischemia Hypertension Hypotension
Phenylephrine	Typically used as emergency bolus to correct acute hypotension. Hypotension (any) Used to increase MAP during hypotension in aortic stenosis. Used to decrease LVOT gradient in HCM Used to correct hypotension caused by the simultaneous ingestion of sildenafil and nitrates	Bolus: 0.1 to 0.5 mg IV every 10 to 15 min Infusion: 0.4 to 9.1 μg/kg/min Safe for peripheral use	+++++	0	0	N/A	Immediate and pronounced increase in MAP.	Reflex bradycardia Hypertension (especially with nonselective β-blockers) Severe peripheral and visceral vasoconstriction Tissue necrosis with extravasation
Milrinone (Phosphodiesterase Inhibitor)	Heart failure, acute Heart failure, decompensated chronic.	Bolus: 50 μg/kg bolus over 10 to 30 min Infusion: 0.375 to 0.75 μg/kg/min.	0	0	0	0	PDI (Phosphodiesterase Inhibitor). Potent inotrope. Induces vasodialtion. Results in reduced preload, afterload and SVR.	Ventricular arrhythmias Hypotension Myocardial ischemia Torsade des pointes Accumulates in renal failure (dose adjustment necessary)
Amrinone	Heart failure, acute Heart failure, decompensated chronic	Bolus: 0.75 mg/kg over 2 to 3 min Infusion: 5 to 10 μg · kg⁻¹ · min⁻¹	0	0	0	0	PDI (Phosphodiesterase Inhibitor). Rarely used due to side effects.	Arrhythmias, enhanced AV conduction Hypotension Thrombocytopenia Hepatotoxic
Vasopressin	Shock (any) Cardiac arrest	Infusion: 0.01–0.1 U/min (common fixed dose 0.04 U/min) Bolus (IV): 40 U	0	0	0	0	Vasopressin stimulates V₁ receptors (vascular smooth muscle) and V₂ (renal). V1 stimulation induces vasoconstriction, and V2 increases renal water reabsorption. Vasopressin increases SVR with no significant effect on CO. Vasopressin potentiates the vascular effect of norepinephrine.	Arrhythmias Hypertension Decreased CO (at doses >0.4 U/min) Cardiac ischemia Severe peripheral vasoconstriction causing ischemia (especially skin) Splanchnic vasoconstriction
Levosimendan	Heart failure, decompensated chronic	Loading dose: 12–24 μg/kg over 10 min Infusion: 0.05–0.2 μg/kg/min	0	0	0	0	Levosimendan is a calcium sensitizer that enhances ventricular contractility and induces peripheral arteriolar and venous vasodilation.	Enhanced AV conduction Hypotension

CO = cardiac output, AF = atrial fibrillation, SVR = systemic vascular resistance, MAP = mean arterial pressure.

Receptors of catecholamines

Alpha-1 adrenergic receptors: expressed in vascular smooth muscle cells, activation leads to vasoconstriction and increased SVR.
Beta-1 adrenergic receptors: expressed in the myocardium; excitation results in increased contractile force (contractility) and increased chronicity.
Beta-2 adrenergic receptors: expressed in the vascular smooth musle cells and leads to vasodilation.
D1 and D2 (Dopamine receptors): Excitation of D1 and D2 dopaminergic receptors in the kidney and splanchnic vasculature induces renal and mesenteric vasodilation.

NB: Rapid blood pressure alterations may induce reflexive autonomic responses that affect the final hemodynamic result.

Dobutamine is a synthetic catecholamine.

Cardiovascular Medicine

Inotropes and Vasopressors: Doses, indications, contraindications and effects