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Epinephrine – 100 Years of Controversy

February 15, 2021

Written by Clay Smith

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Epinephrine for cardiac arrest improves ROSC and survival but may only benefit long-term neurologically intact outcomes when given early in patients with non-shockable rhythms.

Why does this matter?
One thing I have learned – I shouldn’t be overly dogmatic about a lot of things…especially epinephrine for arrest. Epinephrine is recommended as improving survival in the 2020 AHA resuscitation guidelines. But does it really? If so, which patients are most likely to benefit?

Over 100 years and still not crystal clear
Since epinephrine was initially isolated in 1894, it was quickly seen as a potential cardiac arrest drug. Early experiments in 1905 performed in dogs showed it improved ROSC but not long-term neurological recovery. Fifty years later, similar experiments were repeated to refine dosing. With the advent of ACLS in 1974, the experiments showing improved ROSC in dogs at a dosage of 1mg were used as the basis for recommending epinephrine in human cardiac arrest. Since then, multiple retrospective studies have raised questions about the effectiveness of epinephrine, and high dose epinephrine was eventually dropped from ACLS as ineffectual. Then prospective studies were done, culminating in PARAMEDIC-2. Just as in the dog experiments 100 years before, they found increased ROSC but no improvement in long-term neurologically intact survival. In fact, those who did survive seemed to have poorer neurological outcomes. However, there may be subsets of arrest patients who benefit from epinephrine, such as those with PEA or asystole vs shockable rhythms. The 2019 ILCOR guidelines acknowledged this nuance; the 2019 AHA interim update didn’t. This review was written in response to the 2019 AHA update. Since then, the 2020 AHA guidelines have been published and mention that early epinephrine may be particularly beneficial when given early in patients with non-shockable rhythms. After 100 years, we are still not completely sure how to use this drug. But I’m optimistic we will firm this up over the next century.

After a century, Epinephrine’s role in cardiac arrest resuscitation remains controversial. Am J Emerg Med. 2021 Jan;39:168-172. doi: 10.1016/j.ajem.2020.08.103. Epub 2020 Oct 21.

What are your thoughts?