Out-of-hospital cardiac arrest (OHCA) leads to over 300,000 deaths every year in North America. Many OHCA are due to ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), which are generally considered to have the best prognosis during cardiac arrest due to their responsiveness to defibrillation. However, attempts at defibrillation during cardiac arrest frequently result in non-sustained return of spontaneous circulation (ROSC), and VF or pulseless VT commonly persist or recur after defibrillation. Amiodarone and lidocaine are used to promote defibrillation of VF or pulseless VT, and to prevent recurrences. Previous trials demonstrated patients with OHCA who received amiodarone were more likely than those who received placebo or lidocaine to have ROSC, and to survive to hospital admission. However, amiodarone’s effect on survival to hospital discharge, or neurologic outcome are uncertain.
Does the use of amiodarone or lidocaine during OHCA with shock-refractory VF or pulseless VT have an effect on survival to hospital discharge?
Patients from 55 emergency medical service agencies in 10 North American sites. Patients were 18 years of age or older with nontraumatic OHCA and shock-refractory VF or pulseless VT, defined as confirmed persistent (nonterminating) or recurrent (restarting after successful termination) VF or pulseless VT after one or more shocks anytime during resuscitation (inclusive of rhythms interpreted as being shockable by an automated external defibrillator).
Amiodarone 300 mg IV (150 mg if patient < 45.5 kg) or Lidocaine 120 mg IV (60 mg if patient < 45.4 kg)
0.9% Normal Saline IV
Primary: Survival to hospital discharge
Secondary: Favorable neurologic function at discharge
Multicenter randomized, double-blind, placebo controlled, prehospital trial with intention to treat analysis
Receipt of open-label amiodarone or lidocaine during resuscitation, known hypersensivity to amiodarone or lidocaine, an advance directive, member of protected population (child, pregnant, prisoner), study-provided bracelet provided to those who wish to be excluded from participation, traumatic cardiac arrest
- 37,889 patients with out-of-hospital cardiac arrest were assessed for eligibility
- 4,653 were included in the intention to treat analysis
- 3,026 patients were included in primary analysis
Survival to hospital discharge (No Statistically Significant Difference)
- Amiodarone 24.4%
- Lidocaine 23.7%
- Placebo 21%
- Amiodarone vs Placebo 3.2% difference (95% CI -0.4 – 7.0; p = 0.08)
- Lidocaine vs Placebo 2.6% difference (95% CI -1.0 – 6.3%; p = 0.16)
- Amiodarone vs Lidocaine 0.7% difference (95% CI -3.2 – 4.7%; p = 0.70)
- Neurologic outcomes were similar in all groups
- Patients who received antidysrhythmic drugs received fewer shocks after the first dose of the trial drug, received fewer rhythm-control medications during hospitalization, and required less CPR during hospitalization.
- Active drugs were associated with a higher rate of survival to hospital discharge if the cardiac arrest was witnessed (P = 0.05).
- 27.7% for amiodarone
- 27.8% for lidocaine
- 22.7% for placebo
- Amiodarone vs Placebo 5% (95% CI 0.3 – 9.7; p = 0.04)
- Lidocaine vs Placebo 5.2% (95% CI 0.5 – 9.9; p = 0.03)
- Double-blinded, randomized clinical trial
- Multicenter increasing external validity
- Baseline characteristics between groups were evenly matched
- 99.5% Patient Follow up
- Post arrest care was not standardized between hospitals and this could create imbalances between trial groups
- Trial was powered to detect a 6% absolute differences in survival to hospital discharge. It is possible that there is a smaller difference that is a true difference but this study cannot determine this.
- Selection bias could have influenced trial enrollment
- Drug delivery may have been too late to overcome the metabolic consequences of prolonged cardiac arrest (mean time from arrest to drug treatment was 19.3 minutes).
" Overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival or favorable neurologic outcome than the rate with placebo among patients with out-of-hospital cardiac arrest due to initial shock-refractory ventricular fibrillation or pulseless ventricular tachycardia.”
This trial failed to demonstrate a statistically significant benefit in the primary outcome: survival to discharge. Although subgroup analysis shows interesting trends, there is little data to support using antidysrhythmics in OHCA due to shock resistant VF or pulseless VT when looking at patient centered outcomes (survival to hospital discharge and good neurologic outcomes). Instead, pre-hospital providers should focus primarily on delivering interventions proven to be effective, like high quality chest compressions and defibrillation.
Potential Impact To Current Practice
The results of this study should lead to re-consideration of the use of amiodarone or lidocaine in patients with refractory VF or pulseless VT in OHCA. Future iterations of ACLS will have to incorporate this high-quality data with prior evidence.
The use of amiodarone or lidocaine during OHCA with shock refractory VF or pulseless VT has no significant benefit over placebo, when focused on patient centered outcomes.
ScanCrit: CPR and Amiodarone
EM Nerd: The Case of the Perfect Imperfection
EM Lit of Note: Amiodarone, Lidocaine or . . . Nothing
The Bottom Line: Amiodarone, Lidocaine or Placebo in Out-of-Hospital Cardiac Arrest
St. Emlyn’s: JC: Arrested Developments
Kudenchuk PJ et al. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. NEJM 2016. PMID: 27043165
Joglar JA, Page RL. Out-of-Hospital Cardiac Arrest – Are Drugs Ever the Answer? NEJM 2016. PMID: 27042874