In a patient with cardiac arrest and a shockable rhythm who has already received an initial dose of 300 mg of amiodarone, should the second dose of 150 mg be given immediately after the initial bolus or after another shock?

Timing of Second Amiodarone Dose in Cardiac Arrest

Give the 150 mg dose of amiodarone after another shock if VF/pVT persists or recurs—not immediately after the initial 300 mg bolus. 1, 2

Dosing Algorithm for Refractory VF/pVT

The 2018 American Heart Association ACLS guidelines specify the following sequence for amiodarone administration:

• First dose: 300 mg IV/IO bolus after the third unsuccessful defibrillation attempt 1
• Second dose: 150 mg IV/IO bolus for persistent or recurrent VF/pVT after additional shock(s) 1, 2

The second dose is administered when the rhythm remains refractory to defibrillation or when VF/pVT recurs after initial conversion, not as an immediate follow-up to the first bolus. 2

Critical Context on Timing

The optimal timing of antiarrhythmic administration in relation to shock delivery is explicitly acknowledged as unknown by the AHA. 1 The guidelines state that "the optimal sequence of ACLS interventions for VF/pVT cardiac arrest, including administration of a vasopressor or antiarrhythmic drug, and the timing of medication administration in relation to shock delivery are not known." 1

However, the standard ACLS algorithm follows this pattern:

• Continue CPR cycles with rhythm checks every 2 minutes 2
• Deliver shocks for persistent VF/pVT 2
• Administer the second 150 mg dose when VF/pVT persists after additional defibrillation attempts 2

Evidence on Total Amiodarone Dosing

Recent observational data suggests that 300 mg total may be sufficient compared to 450 mg (300 mg + 150 mg). A 2025 study found that patients receiving 300 mg amiodarone had higher rates of ROSC at ED arrival (30.8% vs 24.2%, p=0.0234) compared to those receiving 450 mg, though survival to discharge was similar. 3 This raises questions about whether the second dose is always necessary, though current guidelines still recommend it for persistent arrhythmias. 1, 2

Common Pitfalls

• Do not administer both doses back-to-back: The second dose is reserved for ongoing refractory rhythm, not given prophylactically 1, 2
• Do not delay CPR to administer medications: Continue high-quality compressions with minimal interruptions 1, 2
• Monitor for hypotension and bradycardia: These are the most common adverse effects requiring dose adjustment or discontinuation 4, 5