What is the recommended isoprenaline (isoproterenol) infusion dose and titration for an adult with symptomatic bradycardia when atropine is ineffective or contraindicated?

Isoproterenol Infusion for Symptomatic Bradycardia

For symptomatic bradycardia refractory to atropine, initiate isoproterenol at 2 mcg/min IV and titrate upward by 2 mcg/min every 2–5 minutes based on heart rate response, with a typical effective range of 2–10 mcg/min and a maximum of 20 mcg/min. 1

Treatment Algorithm

First-Line: Atropine

• Administer atropine 0.5–1 mg IV push immediately for any patient with symptomatic bradycardia (altered mental status, chest pain, hypotension, acute heart failure, or shock), repeating every 3–5 minutes up to a maximum total dose of 3 mg. 1, 2
• Doses <0.5 mg may paradoxically worsen bradycardia through central vagal stimulation and must be avoided. 1, 2

Second-Line: Chronotropic Infusions When Atropine Fails

Isoproterenol is a reasonable alternative to dopamine or epinephrine for atropine-refractory bradycardia, particularly when you want pure chronotropic and inotropic effects without vasopressor activity. 1

Isoproterenol Dosing Protocol

• Starting dose: 2 mcg/min IV infusion 1, 3
• Titration: Increase by 2 mcg/min every 2–5 minutes based on heart rate and blood pressure response 1
• Typical effective range: 2–10 mcg/min 1, 3
• Maximum dose: 20 mcg/min (higher doses risk excessive vasoconstriction and arrhythmias) 1
• Preparation: Mix 1 mg isoproterenol in 100 mL normal saline; infuse at maximum 75 mL/h to deliver 2–12 mcg/min 3

Alternative Chronotropic Agents

• Dopamine: 5–10 mcg/kg/min IV, titrated by 2–5 mcg/kg/min every 2 minutes to a maximum of 20 mcg/kg/min; preferred for most situations when both chronotropic and inotropic support with some vasopressor effect is needed 1
• Epinephrine: 2–10 mcg/min IV (or 0.1–0.5 mcg/kg/min); preferred when severe hypotension requires strong combined chronotropic, inotropic, and vasopressor effects 4, 1

Critical Contraindications for Isoproterenol

Isoproterenol is absolutely contraindicated in any patient with suspected or confirmed coronary ischemia, acute coronary syndrome, or recent myocardial infarction. 3

• Isoproterenol increases myocardial oxygen demand through β₁-adrenergic effects while simultaneously decreasing coronary perfusion pressure through β₂-mediated systemic vasodilation, creating a dangerous supply-demand mismatch. 3
• In acute MI or ischemia, raising heart rate with any chronotropic agent can worsen ischemia or enlarge infarct size. 1

When Isoproterenol May Be Preferred Over Dopamine or Epinephrine

Isoproterenol provides pure β-adrenergic chronotropic and inotropic effects without α-mediated vasoconstriction, making it preferable in ischemic cardiomyopathy when coronary disease has been excluded and when afterload reduction is desirable. 1

• In post-heart-transplant patients, isoproterenol is more appropriate than atropine (which may cause paradoxical high-degree AV block in 20% of transplant recipients) and may be preferred over dopamine or epinephrine. 1, 3
• The AV node is more sensitive than the sinus node to isoproterenol; lower doses (as low as 0.007 mcg/kg/min) can significantly improve AV nodal conduction before achieving target heart rate increases. 5

Situations Where Isoproterenol (and All Chronotropic Agents) Are Ineffective

• Type II second-degree AV block (Mobitz II) with wide QRS complex indicates infranodal block; chronotropic agents do not improve conduction below the AV node and may be harmful—transcutaneous pacing is required instead. 1
• Third-degree AV block with wide QRS complex is similarly unresponsive to pharmacologic therapy. 1

Transcutaneous Pacing

Do not delay transcutaneous pacing in hemodynamically unstable patients while administering multiple doses of atropine or waiting for chronotropic infusions to take effect. 1

• Transcutaneous pacing receives a Class IIa recommendation for unstable bradycardia unresponsive to atropine and serves as a bridge to transvenous or permanent pacing. 1

Monitoring During Isoproterenol Infusion

• Continuous ECG monitoring is mandatory to assess rhythm response and detect emergent arrhythmias. 3
• Monitor heart rate, blood pressure, and symptoms every 2–5 minutes during titration. 1, 3
• Target heart rate is approximately 60 bpm; avoid aggressive rate increases that could raise myocardial oxygen demand. 1
• Watch for signs of excessive dosing: tachycardia >100 bpm, worsening chest pain, hypotension (from excessive vasodilation), or ventricular arrhythmias. 3

Paradoxical Bradycardia

Isoproterenol can rarely cause paradoxical bradycardia (7% incidence) through reflex vagal stimulation, particularly in young patients with hypervagotonia. 6

• Sinus or junctional bradycardia during isoproterenol infusion is more common in young patients (mean age 40 years) studied for unexplained syncope without structural heart disease. 6
• Isoproterenol may also unmask organic AV conduction disturbances, revealing second-degree AV block (supraHisian or infraHisian) in older patients with exercise-related syncope. 6

Common Pitfalls to Avoid

• Do not use isoproterenol as first-line therapy; atropine must be attempted first (up to 3 mg total). 1, 3
• Do not use isoproterenol in any patient with suspected coronary ischemia; the drug's mechanism worsens oxygen supply-demand mismatch. 3
• Do not exceed 20 mcg/min; higher doses cause excessive side effects without additional chronotropic benefit. 1
• Do not rely on isoproterenol alone in critically unstable patients; prepare transcutaneous pacing simultaneously. 1