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PARAMEDIC2 – Epinephrine in Arrest RCT

July 23, 2018

Written by Clay Smith

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Epinephrine for out-of-hospital cardiac arrest (OHCA) improved overall 30-day survival (3.2%, epi vs 2.4%, placebo) but did not improve survival to discharge with a good neurological outcome.  In fact, more patients who received epinephrine and survived had severe neurological impairment than in the placebo group.

Why does this matter?
The literature has been back on forth on epinephrine.  Studies suggest it improves return of spontaneous circulation (ROSC), but those who survive long-term are neurologically devastated.  This RCT was designed to clear this up.

Epi – It depends on how you look at it
This was a large RCT from the UK with 8014 adult, non-pregnant people with OHCA who received standard resuscitation care and either epinephrine or saline as placebo.  Groups were well matched.  Those who made it to the hospital received standard ICU care, including targeted temperature management.  For the primary outcome, epinephrine significantly improved 30-day survival over placebo: 3.2% vs 2.4%, respectively.  Consistent with prior studies, ROSC was much higher in the epinephrine group vs placebo: 36% vs 12%, respectively.  However, there was no improvement in survival to discharge with good neurological outcome (defined as modified Rankin scale [mRS] ≤3) with epinephrine vs placebo: each around 2% with no statistical difference.  Survivors to hospital discharge with severe neurological injury (mRS 4 or 5) were more common in those who received epinephrine vs. placebo: 31% (39/126) vs 18% (16/90), respectively.  See Figure.


From cited article: Survival with a Favorable Neurologic Outcome at Hospital Discharge. (Note: mRS of 6 = dead)

From cited article: Survival with a Favorable Neurologic Outcome at Hospital Discharge. (Note: mRS of 6 = dead)


Now we must debate if getting more survivors, at the cost of them being neurologically devastated, is the right thing to do.  Prior to the study they assessed public opinion and found that patients, “identified survival with a favorable neurologic outcome to be a higher priority than survival alone.”  Epi seems to be good for the heart but not the brain.

The authors also suggested we prioritize treatments with the most value in OHCA.  The NNT was 112 for survival with epinephrine.  Whereas for early defibrillation the NNT = 5 ; for early recognition of arrest, NNT = 11; for bystander CPR, NNT = 15.

A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest.  N Engl J Med. 2018 Jul 18. doi: 10.1056/NEJMoa1806842. [Epub ahead of print].  This is a free full text access article from NEJM.
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As you might have guessed, this blockbuster article already has garnered attention in the #FOAMed world.

Reviewed by Thomas Davis


4 thoughts on “PARAMEDIC2 – Epinephrine in Arrest RCT

  • Interesting, but this makes me wonder if there is a middle ground where epinephrine is improves survival without causing neurological complication. Perhaps a lower dose can be used to find this point.

  • WHAT EVERYONE FAILS TO REALIZE – The epinephrine in all these cases was delivered VERY late in the cardiac arrest. On average of 15 minutes after arrival! (Not sure if they had to weight for arrival of a special unit).

    This study is comparing the effects of loading a mostly dead body up with epi and seeing if you can rev the half-dead tissues into temporarily functioning a bit longer.

    • Earlier is better. But as you said, they were all late. The groups were well matched. Other things being equal, the Epi group did worse. I wonder what would have happened had it been given earlier.

What are your thoughts?