Here it is: PARAMEDIC-2 study paper - Epi vs. placebo

medicsb

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https://www.nejm.org/doi/full/10.1056/NEJMoa1806842


  • A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest
    • Gavin D. Perkins, M.D., Chen Ji, Ph.D., Charles D. Deakin, M.D.,et al.
  • for the PARAMEDIC2 Collaborators*

Abstract
Background


Concern about the use of epinephrine as a treatment for out-of-hospital cardiac arrest led the International Liaison Committee on Resuscitation to call for a placebo-controlled trial to determine whether the use of epinephrine is safe and effective in such patients.

Methods
In a randomized, double-blind trial involving 8014 patients with out-of-hospital cardiac arrest in the United Kingdom, paramedics at five National Health Service ambulance services administered either parenteral epinephrine (4015 patients) or saline placebo (3999 patients), along with standard care. The primary outcome was the rate of survival at 30 days. Secondary outcomes included the rate of survival until hospital discharge with a favorable neurologic outcome, as indicated by a score of 3 or less on the modified Rankin scale (which ranges from 0 [no symptoms] to 6 [death]).

Results
At 30 days, 130 patients (3.2%) in the epinephrine group and 94 (2.4%) in the placebo group were alive (unadjusted odds ratio for survival, 1.39; 95% confidence interval [CI], 1.06 to 1.82; P=0.02). There was no evidence of a significant difference in the proportion of patients who survived until hospital discharge with a favorable neurologic outcome (87 of 4007 patients [2.2%] vs. 74 of 3994 patients [1.9%]; unadjusted odds ratio, 1.18; 95% CI, 0.86 to 1.61). At the time of hospital discharge, severe neurologic impairment (a score of 4 or 5 on the modified Rankin scale) had occurred in more of the survivors in the epinephrine group than in the placebo group (39 of 126 patients [31.0%] vs. 16 of 90 patients [17.8%]).

Conclusions
In adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival than the use of placebo, but there was no significant between-group difference in the rate of a favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group. (Funded by the U.K. National Institute for Health Research and others; Current Controlled Trials number, ISRCTN73485024.)
 

NPO

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A large percentage of the patients were in nonshockable rhythms. I wonder if there would be greater results with just the shockable rhythm patients.

We are about to change our cardiac arrest protocols and epi will be a big change in our new protocols. I believe we're going to 1mg one time.
 

PotatoMedic

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And it shows what most have assumed. You get more heart beats back but less humans.
 

mgr22

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We are about to change our cardiac arrest protocols and epi will be a big change in our new protocols. I believe we're going to 1mg one time.

That's interesting, NPO. Care to share the other changes?
 

NPO

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That's interesting, NPO. Care to share the other changes?
I'll know for sure this week. Our clinical standards comitee will be meeting to go over the changes and evaluate how to structure the new protocols.

We are going to more rhythm specific protocols.

- No ACLS drugs in traumatic arrest.
- Dopamine in traumatic arrest for pseudo-PEA
- Esmolol for refractory VF.

To name a few.
 

EpiEMS

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So exciting that this paper is finally out!

Here's hoping it leads to some critical reevaluation of what's important, both from the care perspective and the "what outcomes do we care about" POV.
 

NPO

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I'm really not all that moved by the results. The margins are there, but they're not large, and it doesn't tell us a whole lot.

The epinephrine group had significantly higher ROSC (36% vs 11%), but also marginally higher rates of favorable neurologic outcome (2.1% vs 1.6%)

Did the epinephrine group have more survivors because they simply cast a wider net (more patients successfully rescusitated).

A lot of people were waiting for this study to prove that epi is killing brains left and right. I don't think it shows that at all.

I think sympathomimetic play a role in successful rescusitation. But maybe 1mg of epinephrine every 3-5 minutes isn't the answer.

Steve Weingart just put out a podcast where he briefly talked about the resurgence of vasopressin. Food for thought.
 

StCEMT

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Has there ever been a test on epi dosing? I would never give 1mg to someone that's alive, so why the extra dose just because they are dead?

I don't think epi is killing brains necessarily, but dumping 1mg into someone who hasn't been perfusing and causing cerebral vasoconstriction doesn't seem helpful either.
 

EpiEMS

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Has there ever been a test on epi dosing? I would never give 1mg to someone that's alive, so why the extra dose just because they are dead?
Here's one old RCT comparing 0.02 mg/kg vs. 0.2 mg/kg. No difference in ROSC, discharge, or neurologically favorable discharge.

I'll see what else I can dig up.
 

E tank

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Has there ever been a test on epi dosing? I would never give 1mg to someone that's alive, so why the extra dose just because they are dead?

I don't think epi is killing brains necessarily, but dumping 1mg into someone who hasn't been perfusing and causing cerebral vasoconstriction doesn't seem helpful either.

I wonder how much cerebral vasoconstriction occurs with epi in out of hospital arrests. I've read the animal model studies, but they don't really reflect reality in these conditions. Between a low/no flow state and hypercarbia, the cerebral vasculature ought to be pretty dilated. Add to that an acidotic state and a mg of epinepherine isn't as effective as in a normal pH state. The low flow state is enough to hurt the brain as it is...
 

TXmed

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Or maybe while we are all pointing fingers at epi, excessive administration of sodium bicarb is hurting our patients.
 

E tank

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Or maybe while we are all pointing fingers at epi, excessive administration of sodium bicarb is hurting our patients.

I've never heard that...how so? How is "excessive" defined? No challenge here...just not in that loop.
 

Carlos Danger

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MonkeyArrow

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I would really love to see someone tackle replicating Meantzelopoulos 2013 (https://www.ncbi.nlm.nih.gov/pubmed/23860985) which showed significantly better ROSC and survival with CPC 1/2 after a vasopressin-epinephrine-steroids cocktail over just epi in an in-hospital cohort. It looks so promising I have no idea why this hasn't garnered increased attention/studies.

Potentially related, the time from scene arrival to first trial drug administration was 13 minutes, and time from call to admin 21 minutes. That seems way too long to me. Maybe epi (and some smaller studies have mixed opinions on this) is more effective earlier in arrest.
 

Summit

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I haven't seen sodium bicarb in arrest in years... well no I take it back... I saw it in a heroic measures resuscitation a year ago about 1 hour in... long code on a young guy.

Normally I see it post-ROSC to temporize pressor efficacy in acidosis...
 

NPO

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I haven't seen sodium bicarb in arrest in years... well no I take it back... I saw it in a heroic measures resuscitation a year ago about 1 hour in... long code on a young guy.

Normally I see it post-ROSC to temporize pressor efficacy in acidosis...
I've used it once, for suspected severe acidosis.

It worked, but that's pretty anecdotal.
 

E tank

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Normally I see it post-ROSC to temporize pressor efficacy in acidosis...

I use it that way in severely acidotic, bleeding patients as a temporizing measure to help with pressors until I can replace volume and red cell mass...Usually in these patients, COPD and CO2 elimination is a problem, so I trade a metabolic acidosis for a respiratory one, which is better tolerated so I do it. As far as the hypertonic nature of NaHCO3, I don't really care about that until the serum sodium creeps up to around 150. By then things are under control or the patient is dead...
 
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