Why is adrenaline (epinephrine) administered during a second shock in cardiac arrest?

Timing of Epinephrine in Shockable Cardiac Arrest Rhythms

For cardiac arrest with shockable rhythms (VF/pVT), epinephrine should be administered after initial defibrillation attempts have failed, typically after the second or third shock, because the priority is immediate defibrillation and high-quality CPR, with epinephrine playing a secondary role once electrical therapy proves unsuccessful. 1, 2, 3

The Rationale: Rhythm-Specific Strategy

The timing of epinephrine differs fundamentally based on the initial cardiac rhythm:

For Shockable Rhythms (VF/pVT):

• Defibrillation takes priority over medication administration, as electrical therapy is the definitive treatment for ventricular fibrillation and pulseless ventricular tachycardia 1
• The American Heart Association provides only a Class 2b (weak) recommendation for epinephrine timing in shockable rhythms, acknowledging insufficient evidence for optimal timing in relation to defibrillation 1, 3
• Pediatric guidelines specifically state: administer epinephrine during CPR after the second shock (4 J/kg), continuing every 3-5 minutes thereafter 1

For Non-Shockable Rhythms (PEA/Asystole):

• Epinephrine should be given as soon as feasible after establishing vascular access (Class 2a recommendation) 1, 2, 3
• This represents a fundamentally different approach because these rhythms cannot be defibrillated 4

The Physiologic Mechanism

Why Epinephrine Works:

• Alpha-adrenergic effects increase coronary perfusion pressure (aortic diastolic pressure minus right atrial pressure), which is the critical mechanism for restoring spontaneous circulation 5
• Epinephrine significantly increases ROSC rates by 151 more patients per 1,000 compared to placebo (RR 2.80,95% CI 1.78-4.41) 2
• It increases survival to hospital admission by 124 more patients per 1,000 (RR 1.95% CI 1.34-2.84) 2

Why Timing Matters in Shockable Rhythms:

• Beta-adrenergic stimulation increases myocardial oxygen consumption in fibrillating myocardium, which is potentially deleterious 5
• The heart needs to be defibrillated first; giving epinephrine before attempting defibrillation may complicate the electrical therapy without providing benefit 1
• CPR provides coronary perfusion that increases the likelihood of successful defibrillation with subsequent shocks 1

The Practical Algorithm for Shockable Rhythms

Initial Management (First 4-6 Minutes):

1. Immediate defibrillation at 2 J/kg (pediatric) or appropriate adult dose 1
2. Resume CPR immediately for 2 minutes after shock delivery 1
3. Second shock at 4 J/kg (pediatric) or appropriate adult dose if shockable rhythm persists 1
4. Resume CPR immediately for 2 minutes 1

After Failed Initial Defibrillation Attempts:

• Administer epinephrine 1 mg IV/IO (0.01 mg/kg in pediatrics, max 1 mg) during chest compressions 1, 2
• Repeat every 3-5 minutes throughout the resuscitation 1, 2
• Consider antiarrhythmics (amiodarone or lidocaine) after the third shock 1

Evidence Quality and Controversies

The Evidence Gap:

• There is insufficient evidence to make a strong recommendation regarding optimal epinephrine timing in shockable rhythms, particularly in relation to defibrillation 1
• The relationship between timing of defibrillation and timing of epinephrine remains unknown in studies of shockable rhythms 1
• Most observational studies have significant design flaws, including inability to determine the precise relationship between defibrillation attempts and epinephrine administration 1

The Neurological Outcome Concern:

• While epinephrine increases ROSC and short-term survival, its effect on favorable neurological outcomes remains uncertain 3, 6, 7
• The American Heart Association acknowledges the fundamental challenge in determining the likelihood of favorable versus unfavorable neurological outcome at the time of arrest 2
• Some evidence suggests epinephrine may not provide meaningful neurological recovery despite improving survival rates 6, 7

Critical Pitfalls to Avoid

Common Errors:

• Do not delay defibrillation to administer epinephrine in shockable rhythms 1
• Minimize interruptions in chest compressions - epinephrine should be administered during ongoing compressions, not as a reason to pause CPR 1
• Do not use high-dose epinephrine (>1 mg in adults, >0.01 mg/kg in pediatrics) routinely, as it increases ROSC but does not improve survival or neurological outcomes and may be harmful 1, 2, 3
• Avoid confusing shockable and non-shockable protocols - the timing strategy is fundamentally different 1, 2, 3

Dosing Specifics:

• Standard adult dose: 1 mg IV/IO every 3-5 minutes 2, 3
• Pediatric dose: 0.01 mg/kg (0.1 mL/kg of 1:10,000 concentration), maximum 1 mg 1
• No maximum cumulative dose is defined, though doses above 3 mg may be associated with unfavorable neurological outcomes 2