Amiodarone vs. Lidocaine vs. Placebo

The results are in. In an article, Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest, published in yesterday’s New England Journal of Medicine by Peter J. Kudenchuk, M.D., Siobhan P. Brown, Ph.D, and others, the results of a major randomized double blinded study involving paramedics from ten major cities in North America (The Resuscitation Outcomes Consortium (ROC)), and enrolling over 3,000 patients, concluded there was no significant difference in outcomes between the drugs and a placebo when administered to patients in refractory v-fib or pulseless v-tach arrests.

Here are the numbers on survival to hospital discharge:

Amiodarone   24.4%

Lidocaine  23.7%

Placebo 21.0%

While amio and lido outdid placebo, the margin was too small to be statistically significant.

The researchers, who thought the drugs would show a greater effect, now admit that they should have done a larger study. If these results had held true over 9000, not 3000, patients they would have achieved significance. But then perhaps, had they enrolled 9,000 the gaps might have narrowed and no difference would have again been confirmed.

Whenever large studies like this come out, I always look for the accompanying editorial, which tries to explain the results in easier terms for a layman like me to understand.

In Out-of-Hospital Cardiac Arrest” Are Drugs Ever the Answer? Jose A. Joglar, M.D., and Richard L. Page, M.D, write:  The data do not support the use of amiodarone or lidocaine for all patients, but, although they are not absolutely conclusive, the data suggest that EMS personnel should consider these agents when the arrest is witnessed. There is no signal from the data as to which drug might be preferable, however.

The writers mention the subgroup of patients whose arrests were witnessed by bystanders, which represented approximately 66% of the total patients.  Here’s how the numbers came out with regard to their survival to hospital discharge:

Amiodarone 27.7%

Lidocaine 27.8%

Placebo 22.7%

Interesting numbers, but as the writers are cautious to point out, they are still not statistically significant.

The great Rogue Medic  weighed in on the study earlier today.  His post Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest is well worth reading as is everything Rogue writes.

I am anxious to read other commentaries, which will no doubt be forthcoming.

For me and for most medics, I think the take home is we should continue to follow our protocols, do our best to provide excellent compressions, early and timely defibrillation, and spread the word to all about the merits of bystander CPR (which this study again found to be a truly beneficial and provable intervention to cardiac arrest victims). Teach CPR to everyone you know.

As far as amio or lido, get your IV when you can without interfering with compressions and defibrillation, and deliver the drugs (if they are in your protocol) for witnessed arrests.

Be cheered that we are finally doing solid research in EMS and that we are hopefully getting closer to the truth, even if we may still be far from a magic bullet to accompany CPR and defibrillation.

I would love to see a similar trial of epinephrine versus placebo. Lidocaine and Amiodarone appeared to not have any significant harmful effects, I am not certain the same would be shown with epinephrine.


Update to post-


Rogue Medic has pointed out the epi versus placebo study is now being done in England with results due in 2018.

Check out Andrew’s great comments on the Amio, Lido, Placebo study in the comments sections.

Ryan Radecki at Emergency Medicine Literature of Note has his usual astute comments on the this study as well.

Amiodarone, Lidocaine, or … Nothing


  • Rogue Medic says:

    Thank you for the kind words.

    There is a study of epinephrine vs. placebo taking place in the UK – Paramedic2, with results due in late 2018.


  • Andrew DeWolf says:

    Great study, but underpowered for effect as noted. Debate no solved. Looked at refractory VF/VT with right outcomes of survival neuro intact. Only 43% of potentials admitted into trial, 19 minute avg drug delays, heterogenity, and new formulation of amiodarone used. 3% difference can be huge in applied practice for those survivors. Other interesting take home points – placebo required more defibs, survivors re arrested more, and drugs appeared equal lido v Amio. Love the ROC thier work, wish they would have worked out a few of these variables better. Not practice changing yet in my opinion.

  • medicscribe says:

    Thanks for the great comments, Andrew.

    Thanks Rogue for the news about the British study.



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