Isoproterenol (Isuprel)

• Pure β-Agonist: Potent β1 and β2 agonist with strong chronotropic and inotropic effects, plus peripheral vasodilation; minimal α activity
• Modern Use Limited: Primarily for bradyarrhythmias (high-grade AV block, sick sinus) when pacing not available, and torsades de pointes to increase HR and shorten QT
• Hemodynamic Profile: ↑ HR, ↑ contractility, ↓ SVR (β2 vasodilation) → can precipitate or worsen hypotension, especially in vasoplegic or hypovolemic patients
• Dosing: Typical adult IV infusion range 1-20 mcg/min (or 0.01-0.2 mcg/kg/min), titrated to HR and BP
• Bridge Not Definitive: For unstable bradycardia, isoproterenol is a bridge to pacing, not definitive therapy; arrange transvenous or permanent pacing
• CAD Caution: Be cautious in older patients with occult CAD, as aggressive chronotropy can unmask ischemia quickly

• Generic Name: Isoproterenol hydrochloride
• Brand Names: Isuprel, generics

Non-selective β-adrenergic agonist (β1 and β2); catecholamine inotrope and chronotrope

Mechanism of Action:

• Isoproterenol is a synthetic catecholamine acting as a non-selective β-adrenergic agonist
• Stimulates β1 receptors in the heart → positive chronotropy (↑ HR), positive inotropy (↑ contractility), positive dromotropy (↑ AV conduction)
• Stimulates β2 receptors in vascular smooth muscle → vasodilation, particularly in skeletal muscle vasculature → decreased systemic vascular resistance (SVR) and potentially decreased diastolic BP
• Net effect: increased cardiac output driven by increased HR and contractility, often with widened pulse pressure and decreased diastolic pressure
• Essentially no α-mediated vasoconstriction, making it poorly suited as a vasopressor in shock states and may worsen hypotension

Pharmacokinetics (IV):

• Onset: Very rapid, within 1-2 minutes of starting or adjusting infusion
• Half-life: Very short, typically <5 minutes, allowing rapid titration and quick offset
• Metabolism: Primarily by COMT (catechol-O-methyltransferase) in liver and uptake by sympathetic nerve terminals
• Route: Continuous IV infusion usual route for sustained effect

Available Forms:

• IV solution: Typically supplied as 0.2 mg/mL (1:5000) in ampules or vials for dilution
• Diluted in D5W or NS to desired concentration for continuous infusion via pump

IV Isoproterenol Dosing (Adult):

Contraindications:

• Tachyarrhythmias (e.g., ventricular tachycardia, rapid atrial fibrillation) where additional β-stimulation would be harmful
• Angina or acute MI with significant ischemia where tachycardia and increased oxygen demand are poorly tolerated (relative contraindication; may be used cautiously in desperate situations)

Major Precautions:

• Coronary artery disease: isoproterenol can markedly increase myocardial oxygen consumption and precipitate ischemia or infarction
• Severe hypotension or hypovolemia: β2-mediated vasodilation may further lower SVR and diastolic BP; often requires concurrent volume resuscitation and/or vasopressors
• Ventricular arrhythmia risk, especially with high doses or structural heart disease

Common:

• Tachycardia, palpitations
• Tremor, nervousness, headache
• Flushing
• Hypotension (from vasodilation)

Serious:

• Myocardial ischemia or infarction (increased oxygen demand)
• Ventricular arrhythmias (VT, VF)
• Severe hypotension with syncope or shock

Continuous Monitoring:

• Continuous ECG monitoring for HR, rhythm, and arrhythmias
• Continuous blood pressure monitoring (arterial line preferred for accurate diastolic BP)
• Signs of myocardial ischemia (chest pain, ST changes on ECG)

• Symptomatic bradycardia: High-grade AV block or sick sinus syndrome as a bridge to pacing when atropine ineffective and pacing not yet available
• Torsades de pointes: Pause-dependent or bradycardia-associated torsades to increase HR and shorten QT interval (pharmacological overdrive pacing), combined with magnesium and correction of underlying causes
• β-blocker overdose: In some cases under specialist guidance, combined with glucagon, calcium, and high-dose insulin
• EP lab use: Induction of arrhythmias for diagnostic or ablation procedures (protocol-specific)

• 1. Lexicomp. (2024). Isoproterenol: Drug information. Wolters Kluwer.
• 2. American Heart Association. (2020). 2020 American Heart Association guidelines for CPR and emergency cardiovascular care. Circulation, 142(16_suppl_2), S337–S357. https://doi.org/10.1161/CIR.0000000000000916
• 3. Farkas, J. (2022). Bradycardia & AV block. EMCrit Project / IBCC. https://emcrit.org/ibcc/brady/