What is the indication and dosing of an Isoket (isoproterenol) intravenous infusion for symptomatic bradyarrhythmias such as sinus bradycardia, high‑grade atrioventricular block, or cardiogenic shock?

Purpose and Clinical Use of Isoket (Isosorbide Dinitrate) Infusion

Isoket is a nitrate vasodilator used primarily for acute coronary syndromes, heart failure, and hypertensive emergencies—not for bradyarrhythmias. If you are asking about isoproterenol (not Isoket), it is a non-selective β-agonist used as a second-line agent for symptomatic bradycardia refractory to atropine, though it carries significant risks and is largely reserved for electrophysiology laboratory use.

Clarification: Isoket vs. Isoproterenol

• Isoket (isosorbide dinitrate) is a nitrate that causes venodilation and reduces preload—it has no role in treating bradycardia and can actually worsen hypotension in bradycardic patients.
• Isoproterenol is the β-adrenergic agonist used for bradyarrhythmias, and the remainder of this answer addresses isoproterenol based on the expanded question context.

---

Indications for Isoproterenol in Bradyarrhythmias

When to Consider Isoproterenol

• Isoproterenol is a second-line agent for symptomatic bradycardia that has failed to respond to atropine (0.5–1 mg IV, repeated every 3–5 minutes up to 3 mg total). 1
• It is predominantly used in the electrophysiology laboratory (1–20 mcg/min IV) and has only a limited role in acute resuscitation settings. 1
• The drug is reasonable for sinus node dysfunction with symptoms or hemodynamic compromise when atropine has failed (Class IIb recommendation). 1

Critical Contraindications

• Isoproterenol should be avoided in any setting where coronary ischemia is a concern, because it increases myocardial oxygen demand through β₁ effects while simultaneously decreasing coronary perfusion via β₂-mediated vasodilation. 1, 2
• Two randomized trials of isoproterenol as adjunctive therapy in cardiac arrest showed no improvement in return of spontaneous circulation or survival to hospital discharge, reinforcing its limited role in resuscitation. 1

---

Mechanism of Action

• Isoproterenol is a non-selective β-adrenergic agonist that stimulates both β₁ and β₂ receptors. 2
• β₁-mediated cardiac effects include:
  • Enhanced sinus node automaticity and sinoatrial conduction (positive chronotropy—increases heart rate) 2
  • Increased myocardial contractility (positive inotropy—raises cardiac output) 2
  • Improved atrioventricular nodal conduction 2
• β₂-mediated vascular effects include:
  • Pulmonary artery vasodilation, lowering pulmonary vascular resistance 2
  • Peripheral vasodilation, reducing afterload but also potentially worsening hypotension 2

---

Dosing and Administration

Standard Dosing Protocol

• Electrophysiology laboratory use: 1–20 mcg/min IV infusion, titrated to heart rate response. 1
• Acute bradycardia (off-label, second-line): Start at 2–5 mcg/min IV infusion, titrate upward based on heart rate and hemodynamic response.
• The intravenous elimination half-life is extremely short (approximately 2–5 minutes), necessitating continuous infusion to maintain therapeutic effect. 2

Practical Considerations

• Isoproterenol is typically prepared as a continuous infusion due to its rapid metabolism.
• Continuous cardiac monitoring is mandatory to assess heart rate response and detect arrhythmias.
• Blood pressure monitoring is essential, as peripheral vasodilation can cause or worsen hypotension despite increased cardiac output.

---

Clinical Algorithm for Symptomatic Bradycardia

Step 1: Initial Assessment

• Confirm symptomatic bradycardia: heart rate <50 bpm with signs of poor perfusion (altered mental status, ischemic chest pain, acute heart failure, hypotension with systolic BP <80–90 mmHg, syncope, or dyspnea). 3
• Establish IV access, provide supplemental oxygen if hypoxemic, and obtain a 12-lead ECG. 3

Step 2: First-Line Treatment—Atropine

• Administer atropine 0.5–1 mg IV bolus, repeat every 3–5 minutes up to a maximum total dose of 3 mg. 1, 3, 4
• Doses <0.5 mg may paradoxically worsen bradycardia and should be avoided. 4
• Atropine is likely effective for sinus bradycardia, first-degree AV block, and Mobitz I (Wenckebach) second-degree AV block. 3
• Atropine is unlikely effective for Mobitz II second-degree AV block, third-degree AV block with wide QRS, or post-cardiac transplant patients without autonomic reinnervation. 3, 4

Step 3: Second-Line Treatment—Chronotropic Infusions

• If atropine fails, initiate dopamine 5–10 mcg/kg/min IV infusion or epinephrine 2–10 mcg/min IV infusion. 3
• Dopamine is preferred for most situations because it provides dose-dependent chronotropic and inotropic effects with less profound vasoconstriction than epinephrine at lower doses. 3
• Isoproterenol may be considered as an alternative (1–20 mcg/min IV infusion), particularly when pure chronotropic effect is desired without peripheral vasoconstriction, but only if coronary ischemia is not a concern. 1, 2, 3

Step 4: Transcutaneous Pacing

• Transcutaneous pacing is reasonable for unstable patients who do not respond to atropine (Class IIa recommendation). 1, 3
• Do not delay pacing in hemodynamically unstable patients while giving multiple atropine doses. 3

---

Special Clinical Scenarios

Acute Coronary Syndrome

• Isoproterenol is contraindicated in ACS because increased heart rate and contractility raise myocardial oxygen demand while β₂-mediated coronary vasodilation reduces perfusion pressure, potentially extending infarct size. 1, 2
• Atropine should be used cautiously in inferior MI, as excessive heart rate increases may worsen ischemia; limit total dose to 0.03–0.04 mg/kg in patients with coronary artery disease. 3

Heart Transplant Recipients

• Atropine is contraindicated in heart transplant patients without autonomic reinnervation, as it may cause paradoxical high-degree AV block or sinus arrest. 1, 4
• Epinephrine or isoproterenol are preferred agents in this population. 3

Infranodal AV Block

• Isoproterenol (and atropine) are ineffective for Mobitz II second-degree AV block or third-degree AV block with wide QRS, as these represent infranodal conduction disease that does not respond to vagolytic or β-agonist therapy. 3
• Transcutaneous or transvenous pacing is required in these cases. 3

---

Adverse Effects and Monitoring

Common Adverse Effects

• Excessive tachycardia can increase myocardial oxygen consumption and precipitate ischemia or arrhythmias. 2
• Hypotension may occur due to β₂-mediated peripheral vasodilation despite increased cardiac output. 2
• Ventricular arrhythmias (including ventricular tachycardia and fibrillation) can be precipitated, particularly in ischemic or structurally abnormal hearts. 1

Monitoring Parameters

• Continuous ECG monitoring to assess heart rate response and detect arrhythmias. 3
• Frequent blood pressure measurements (every 2–5 minutes during titration). 3
• Clinical assessment of perfusion (mental status, urine output, skin perfusion). 3

---

Common Pitfalls and How to Avoid Them

• Do not use isoproterenol as a first-line agent—atropine should always be tried first unless contraindicated. 1, 3
• Do not use isoproterenol in patients with known or suspected coronary ischemia—the oxygen demand–supply mismatch can be catastrophic. 1, 2
• Do not delay transcutaneous pacing in unstable patients—pharmacologic therapy should not replace pacing when the patient is deteriorating. 3
• Do not confuse Isoket (isosorbide dinitrate) with isoproterenol—they have opposite hemodynamic effects and completely different indications.
• Recognize that paradoxical bradycardia can rarely occur with isoproterenol infusion (7% incidence in one study), particularly in young patients with hypervagotonia or in those with organic AV conduction disturbances. 5