ALPS: Amiodarone, Lidocaine or Placebo Study in OHCA

Background: Many Out-of-Hospital Cardiac Arrest (OHCA) are attributable to ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT). Both are said to be treatable presentations of OHCA, due to their responsiveness to defibrillation. VF and VT can persist or recur after defibrillation with an inverse relationship between the duration of OHCA, the recurrences of arrhythmias, and ultimately resuscitation outcomes.

Amiodarone and lidocaine are both recommended by the advanced cardiovascular life support (ACLS) guidelines to help promote successful defibrillation in refractory ventricular fibrillation or pulseless ventricular tachycardia and to prevent recurrences. In previous randomized controlled trials patients receiving amiodarone vs placebo or lidocaine in OHCA were more likely to have return of spontaneous circulation (ROSC) and to survive to hospital admission. However the effects of amiodarone on survival to hospital discharge or neurologic outcome still remain uncertain. Should we be using anti-dysrhythmic drugs in out-of-hospital cardiac arrest?

What Trial Are we Discussing?

Kudenchuk PJ et al. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. NEJM 2016. [Epub Ahead of Print]

What They Did:

Randomized, double-blind trial from 10 North American Sites

Parenteral amiodarone, lidocaine, or saline placebo along with standard care in adults with non-traumatic OHCA Amiodarone 300 mg IV (150 mg if < 45.4 kg) Lidocaine 120mg IV (60 mg if < 45.5 kg) 0.9% Normal Saline IV

Inclusion: Shock-refractory ventricular fibrillation or pulseless ventricular tachycardia At least one shock Vascular access

Exclusion:

Patient already receiving open-label IV lidocaine or amiodarone during resuscitation

Known hypersensitivity to amiodarone or lidocaine

Known advance directive

Protected populations (child, pregnant, prisoner)

Outcomes:

Primary: Survival to hospital discharge

Secondary: Favorable neurologic function at discharge (modified Rankin Score < 3)

Results:

3026 patients included 974 Amiodarone arm 993 Lidocaine arm 1059 Placebo arm



Strengths:

Double Blinded Randomized Clinical Trial

Baseline characteristics between groups were evenly matched

99.5% Patient Follow up

No differences in pre-shock pauses, compression rate, compression depth, or CPR fraction between groups during first 10 minutes after pad placement

Limitations:

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

Enrollment of patients whose condition at randomization who had little to no chance of survival may have diluted the results of this study

Discussion:

In a subgroup analysis, Amiodarone and Lidocaine had a higher rate of survival to hospital discharge than placebo among patients with witnessed OHCA Amiodarone 27.7% (171 pts) Lidocaine 27.8% (176 pts) Placebo 22.7% (155 pts) 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)

Interestingly amiodarone and lidocaine facilitated termination of ongoing or recurrent ventricular fibrillation or pulseless ventricular tachycardia with fewer shocks than placebo, higher rates of hospital admission, and lesser need for CPR or antiarrhythmic therapies during hospitalization

The time to treatment was 19 minutes on average which could attenuate the effectiveness of antiarrhythmic interventions (i.e. cellular injury and physiological derangements may be irreversible)

Author Conclusion: “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.”

Clinical Take Home Point: Both amiodarone and lidocaine showed similar benefits with respect to short-term outcomes in OHCA due to initial shock refractory ventricular fibrillation or pulseless ventricular tachycardia compared to placebo, but this did not result in a higher rate of survival to hospital discharge or favorable neurologic outcomes.

References:

Kudenchuk PJ et al. Amiodarone, Lidocaine, or Placeboe in Out-of-Hospital Cardiac Arrest. NEJM 2016. [Epub Ahead of Print]

For More Thoughts on This Topic Checkout:

Post Peer Reviewed By: Anand Swaminathan (Twitter: @EMSwami)