First, this is a paper that was just added to the Articles In Press for Resuscitation with the editing not yet completed. Do not fault the authors for the lack of polish. The paper does address some interesting aspects of resuscitation.
ROSC (Return Of Spontaneous Circulation) is the goal for many people.
ROSC is a red herring.
Those of us who think ROSC is important do not seem to understand how much long-term damage we can do in our attempts to get ROSC, or to get ROSC quickly.
This study helps to point out some of the inconsistencies with our ROSC fetish.
Here is a table of the results from the study comparing early epinephrine (≤10 minutes) with late epinephrine (>10 minutes).
Everything highlighted in blue is favoring early epinephrine and statistically significant.
Overall, things look good for early epinephrine, but VF/VT (Ventricular Fibrillation/Ventricular Tachycardia) is most responsive to resuscitation, yet the results for VF/VT never reach statistical significance. VF/VT may also be most associated with an early response
There is only a trend toward better ROSC for VF/VT, but as with the NINDS study of tPA for ischemic stroke, the healthiest patients are in the intervention group, so they are expected to have better outcomes.
With asystole there are survivors with late epinephrine, but no survivors with early epinephrine. What should we make of that? It is far from statistically significant, but there is not even a trend toward more ROSC with early epinephrine.
PEA (Pulseless Electrical Activity) has not just a trend toward more ROSC with early epinephrine, the results are statistically significant.
One of the reasons may be that PEA is sometimes due to assessment problems. We used to call it EMD (Electro-Mechanical Dissociation) because many of us assumed that if no pulse could be palpated, there was no cardiac output. These were termed pseudo-EMD, since imaging could show that there is heart motion, even though there is no palpable pulse.
I have had a handful of patients who were awake and alert, but did not have any palpable pulses. Clearly, EMD is not a description of reality.
How many of these patients are responding to being shaken up, rather than to the mechanical effects of chest compressions in the circulation? We do not know.
Early Epi may increase blood pressure to allow palpation of a pulse in cases with presumed PEA, but who are actually cases of “pseudo-PEA” which have some cardiac output but not enough to be identified clinically.
Then there are the expected confounders in this kind of study. Faster response times would be expected to result in earlier epinephrine and less deterioration of the rhythm to asystole.
The faster response times occur in fewer patients, so there should be a much wider confidence interval/standard deviation. That is not the case, because there is an upper limit on the numbers that can be included. The numbers include response time, time to patient contact, time to establish access, and time to epinephrine. All of those have to be less that 11 minutes combined.
Bystander CPR is much more common with early epinephrine. This may be related the higher incidence of arrest in public, but the bystander CPR rate is about twice as high as the rate of arrest in public.
With early epinephrine we have a decrease from the odds of ROSC to the odds of survival.
With witnessed arrest, bystander CPR, and VF/VT the opposite is true.
With VF/VT the difference is dramatic.
Is this an indication of the effect of epinephrine on survival that we have seen in other studies?
Clearly more work is needed to understand the importance of the timing of epi administration and its impact on outcomes from OHCA.
OHCA is Out of Hospital Cardiac Arrest.
Clearly more work is needed to understand the
importance of the timing effects of epi administration and its impact on outcomes from OHCA.
Why should we assume that it is the timing and not the drug?
Maybe the problem is using such a drug that is so dangerous to the heart to treat heart problems.
Samuel Hahnemann would love this use of epinephrine, just at a much lower dose.
 Rapid Epinephrine Administration Improves Early Outcomes in Out-of-Hospital Cardiac Arrest.
Koscik C, Pinawin A, McGovern H, Allen D, Media D, Ferguson T, Hopkins W, Sawyer K, Boura J, Swor R.
Resuscitation. 2013 Mar 21. doi:pii: S0300-9572(13)00175-5. 10.1016/j.resuscitation.2013.03.023. [Epub ahead of print]
PMID: 23523823 [PubMed – as supplied by publisher]
Koscik, C., Pinawin, A., McGovern, H., Allen, D., Media, D., Ferguson, T., Hopkins, W., Sawyer, K., Boura, J., & Swor, R. (2013). Rapid Epinephrine Administration Improves Early Outcomes in Out-of-Hospital Cardiac Arrest Resuscitation DOI: 10.1016/j.resuscitation.2013.03.023