Drug of Choice for Adult Cardiac Arrest
Epinephrine 1 mg IV/IO every 3-5 minutes is the drug of choice for adult cardiac arrest, regardless of rhythm. 1, 2
Primary Vasopressor: Epinephrine
Standard-dose epinephrine (1 mg) should be administered intravenously or intraosseously every 3-5 minutes during cardiac arrest. 1, 2 The American Heart Association guidelines consistently recommend this as the primary vasopressor across all cardiac arrest rhythms. 1
Timing Based on Rhythm
For shockable rhythms (VF/pVT): Administer epinephrine after the third defibrillation attempt if initial CPR and shocks are unsuccessful. 1, 2 Prioritize defibrillation and high-quality CPR before giving epinephrine. 1
For non-shockable rhythms (asystole/PEA): Give epinephrine as soon as feasible after establishing IV/IO access. 1, 2 Earlier administration is associated with improved return of spontaneous circulation (ROSC) in observational studies. 1
Mechanism and Evidence
Epinephrine works primarily through alpha-adrenergic vasoconstriction, which increases coronary perfusion pressure and cerebral perfusion pressure during CPR. 1 While epinephrine consistently improves ROSC and short-term survival to hospital admission, it does not significantly improve survival to discharge with favorable neurological outcomes. 1, 3
Critical caveat: Despite being the standard of care, epinephrine's benefit on long-term meaningful outcomes remains controversial, with some evidence suggesting potential harm to neurological recovery. 3, 4
High-Dose Epinephrine: Not Recommended
Do not use high-dose epinephrine (>1 mg per dose) routinely. 1 Multiple randomized trials demonstrate that high-dose epinephrine (0.1-0.2 mg/kg) improves ROSC but does not improve survival to discharge or neurological outcomes compared to standard dosing. 1 High-dose epinephrine may only be considered in special circumstances such as beta-blocker or calcium channel blocker overdose. 1
Vasopressin: No Advantage
Vasopressin offers no advantage over epinephrine and is not recommended as a substitute. 1 Multiple randomized trials comparing vasopressin 40 units to epinephrine 1 mg, or the combination of both drugs versus epinephrine alone, showed no difference in ROSC, survival to discharge, or neurological outcomes. 1
The 2010 guidelines allowed vasopressin as an alternative to the first or second dose of epinephrine 1, but more recent evidence has eliminated this recommendation. 1
Exception: Vasopressin-Steroid Combination
One recent trial showed that vasopressin 20 IU plus methylprednisolone 40 mg after the first dose of epinephrine increased ROSC in in-hospital cardiac arrest, though it did not improve 30-day survival or neurological outcomes. 1 This combination may be reasonable for in-hospital arrests but requires further validation. 1
Antiarrhythmic Drugs: Secondary Role
For Refractory VF/Pulseless VT
Amiodarone 300 mg IV/IO is the preferred antiarrhythmic for shock-refractory VF/pVT. 1 Administer after the third shock if VF/pVT persists despite CPR, defibrillation, and epinephrine. 1 A second dose of 150 mg may be given. 1
Lidocaine is an acceptable alternative if amiodarone is unavailable. 1 However, neither drug has been proven to improve survival to discharge or neurological outcomes in the overall population. 1 Both amiodarone and lidocaine improved survival to discharge only in the subgroup of patients with bystander-witnessed arrest, suggesting a time-dependent benefit. 1
Important consideration: Amiodarone can cause significant hypotension and bradycardia, particularly in hemodynamically unstable patients, due to its vasoactive solvents. 1, 5 Consider administering a vasopressor before amiodarone to prevent hypotension. 1
Drugs NOT Routinely Recommended
Sodium bicarbonate: No evidence of benefit in undifferentiated cardiac arrest and may worsen outcomes. 1 Reserve for specific situations like hyperkalemia or tricyclic antidepressant overdose. 1
Calcium: Not recommended routinely and may contribute to ischemic tissue injury. 1 Use only for known hypocalcemia, hyperkalemia, or calcium channel blocker toxicity. 1
Magnesium: Not indicated for routine VF/pVT treatment. 1 Reserve for torsades de pointes. 1
Practical Algorithm
- Confirm cardiac arrest and begin high-quality CPR immediately
- Establish IV/IO access as soon as possible 1, 6
- For VF/pVT: Defibrillate → CPR → Epinephrine 1 mg after 3rd shock → Continue epinephrine every 3-5 minutes → Amiodarone 300 mg if refractory 1, 2
- For asystole/PEA: Epinephrine 1 mg immediately → Continue every 3-5 minutes 1, 2
- Operationally: Give epinephrine every second CPR cycle after the initial dose 1, 2
- Minimize interruptions in chest compressions—drug timing is less important than high-quality CPR 2