April 25, 2016

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)


  • Primary: Survival to hospital discharge
  • Secondary: Favorable neurologic function at discharge (modified Rankin Score < 3)


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



  • 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


  • 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


  • 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.


  1. 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)

Cite this article as: Salim Rezaie, "ALPS: Amiodarone, Lidocaine or Placebo Study in OHCA", REBEL EM blog, April 25, 2016. Available at: https://rebelem.com/alps/.
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Salim Rezaie

Emergency Physician at Greater San Antonio Emergency Physicians (GSEP)
Creator & Founder of REBEL EM
  • janson03
    Posted at 03:29h, 26 April Reply

    That’s not really honest for the authors (the one of the study) to start the conclusion with “Overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival”, sounds like if they want to say that amiodarone is not efficiency and eventually useless.

    They ground their conclusion on the fact we have 0.08 as p-value instead of <0.05, but take a step back and consider what we are talking about : 0.08 is the probability to have the figures they've got if amiodarone does NOT actually differ from saline. That's less than 1 chance out off 10. What does that prove ?

    ANYTHING stricly speaking, and it would even suggest that amiodarone is actually effective. p-value does not prove anything in one study when it is high. It does when it is very (very) low. For boderline cases like this one that's hard to make a conclusion because 0.05 is a subjective threshold, if we take 0.1 as limit value of significance (which is sometimes the case in the industry) the conclusion would have been on the exact opposite where as the facts we observed do not change at all.

    Let's take a step back once again, let's look at subgroups : for exemple we have a good efficiency of amiodarone for EMS-witnessed cardiac arrests. All this suggests that amiodarone is actually efficient and we have to remind that a p-value result from a lot of estimations and a lot of hypothesis we make to ease calculus with convergence theorems and model choices.

    All in all I just want to say that's not serious to conclude the way the authors concluded. A good one would have been : "outcomes suggest that amiodarone is efficient but both of amiodarone and lidocaine deserve more studies to know their exact impact…". I don't know if authors are aware of that and write this conclusion in order to make some noise with their article or if they honestly believe they could write it with those figures, but I am quite sad to see the spreading of this article with a lack of statistical critics.

    PS : thank you for your blog by the way, it's a great great one 🙂

    • Salim Rezaie
      Posted at 17:03h, 26 April Reply

      Hello Janson,
      Agree with your assessment….clearly there is something going on with the use of Amiodarone or Lidocaine that might pan out…unfortunately the study was not large enough to show statistically significant results. It was evident that CPR requirement in the ED and number of shocks were decreased with anti-arrhythmics. Also, in the witnessed OHCA there seemed to be increased survival to discharge vs placebo. So to make the blanket statement that amiodarone and lidocaine don’t work is false…instead what we need is larger studies to help us identify what is signal and what is noise. Appreciate you reading and leaving your comment.


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