Cite this post as:
Scott Weingart, MD FCCM. EMCrit Wee – Abandon Epinephrine?. EMCrit Blog. Published on April 5, 2012. Accessed on March 20th 2025. Available at [https://emcrit.org/emcrit/abandon-epinephrine/ ].
Financial Disclosures:
The course director, Dr. Scott D. Weingart MD FCCM, reports no relevant financial relationships with ineligible companies. This episode’s speaker(s) report no relevant financial relationships with ineligible companies unless listed above.
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I think the more important study, even though a post hoc analysis, it shows what happened to the patients who actually received epinephrine vs. those who did not receive epinephrine. One of the problems with studying such a traditional treatment is that some true believers will violate the protocol, if they have the opportunity. It is not proof, but it strongly suggests harm from epinephrine. Outcome when adrenaline (epinephrine) was actually given vs. not given – post hoc analysis of a randomized clinical trial. Olasveengen TM, Wik L, Sunde K, Steen PA. Resuscitation. 2011 Nov 22. [Epub ahead of print]… Read more »
fantastic additional study. I love the concept of an expiration date on standard of care. It would be a dogma-killer.
Someone would resuscitate the dogma.
With or without epi?
What you are saying makes sense. ROSC w/o neuro intact survival is worse than no ROSC at all. What I would be interested to know is if Epi + NEUROPROTECTION (a.k.a) hypothermia) would improve neuro outcomes while still allowing the increased rosc that you get with epi.
Even more daring, yet sorta unrelated, , it would be interesting to see a study on Intra-Arrest hypothermia, to see if it works better than post-ROSC hypothermia, or what effect it would have.
Braden, given the without hypothermia neuro-intact survival of v-fib (25%) there should be a signal even without the hypothermia unless epi causes harm. What I am saying is 1/4 of the additional ROSC patients should be a neuro-intact survival in the v-fib patients.
Rogue, I may be nit-picking, but I think you are a little off in your interpretation of the Olasveengen post-hoc study, which seemed to better demonstrate why retrospective studies of epinephrine may be inherently biased against epinephrine. Of importance, they found that early responders to CPR & defibrillation (i.e., those with the best chances of survival) are automatically placed in the no-epi cohort, skewing the results in favor of “placebo”. I think it helps build the case for an double-blind RCT, but not the case for epi causing harm (at least not any more than all the other retrospective studies).… Read more »
ScottB,
There were 85 who did not receive epinephrine. 6 did not receive epinephrine because of ROSC, but 55 were for unknown reasons. How many of those did not receive epinephrine because of ROSC prior to epinephrine? Nobody knows.
Those could be eliminated and completely changed the results of the study.
We will not know until there is a large double-blinded randomized placebo controlled study.
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Adrenaline should be removed from the resuscitation of primary cardiac arrest; there is no evidence it increases survival to neurogenically intact hospital discharge and a growing body of evidence it does the opposite or has no effect whatsoever. Saying “BUT IT GETZ TEH ROSC!” means absolutely bloody nothing; resuscitating somebody to the point where they have a pulse is pointless if they’re only going to die a few days or a week later in ICU or if they’re going to be a vegetable, staying dead is far more dignified. Providing an intervention when there is no evidence it actually does… Read more »
There is certain death without ROSC in cardiac arrest. Epinephrine is cheap and easily given. The prehospital research is suggestive both ways for harm and benefit but suffers from the same challenges in providing convincing results as does any other prehospital intervention like tracheal intubation in OHCA. We were sold a myth when Xigris entered the ICU market and wasted a lot of money splashing it around to septic patients. But we still gave it, as it gave us hope of benefit. Its ironic we now poke criticism at an old drug, dirt cheap , that DOES improve ROSC in… Read more »
Minh I believe the true objection is not merely that the drug increases ROSC, but not patient-important outcomes; but instead that if the drug does increase ROSC but not neurological outcome then it might actually be causing harm. Many of the post-arrest sequelae (post-arrest myocardial dysfunction and post-arrest neurological dysfunction) may eventually be traced to over-exuberant epi usage. The real answer is we don’t know. But every defense of epi as a standard of care that should not be abandoned makes it tougher to do a definitive study. Jacob’s PACA trial (which would have answered these questions) was destroyed by… Read more »
Scott, I thought we had thrown out iintubation during arrest but recent posts seem to indicate providers are still intubating during chest compressions! Like trying to do a proper study of cricoid pressure, the definitive epi study in arrest is very challenging to organise. There is no financial incentive to do it. most providers think its biologically plausible to provide some benefit despite recognition it might cause some harm in some cases. its dirt cheap. Xigris was conclusively studied because it was filthy expensive and no one wanted to keep prescribing it until significant benefit was proven. PACA trial was… Read more »
Minh, you know the backstory behind that right? If the trial was conducted as Dr. Jacobs planned, I believe the numbers would have been definitive instead of suggestive.
yeah I know. I have heard Jacobs talk on this to Mel on EMRAP as well as to my buddies in RFDS Western Australia section, where he lives, He actually gives great resuscitation lectures on the latest stuff. It was the closest we came to getting the textbook answers to our questions and he got ethics approval to do it, which I thought was impressive! The longest successful cardiac arrest resuscitation on record was about 90 minutes. that guy got everything. Bystander CPR, ETI, defib, epi, amiodarone, . One ER doc consulted over the phone and told the rescuers to… Read more »
It seems an odd and circular arguement to make, by saying that epinephrine may harm patients who are technically dead already. The supposition of course is that in the ten to twenty percent of cardiac arrest patients who you manage to get ROSC , then giving epi to achieve that, will harm them in the long run.The PACA trial indicated that it was not statistically significantly better than placebo but certainly not worse.i.e harmed patients by lowering survival to discharge, compared with placebo. In fact there was a trend to benefit.
Yep, PACA maybe good–not bad; Japanese trial maybe bad-def. not good. What now? I say take epi out of routine use, keep it as an add-on drug like calcium or bicarb. Then study it for real in blinded RCT and then we will know.
The Japanese study was not placebo controlled like PACA was. I agree. You cannot condemn those who choose or not choose to give epi in cardiac arrest at this juncture in our knowledge time line. interesting proposal to change current standard resucitation guidelines and remove epi from routine use. perhaps interview Jacobs on that one?
PACA did not conclude that epinephrine was not worse. The OR of improved survival was 2.2 (0.7–6.3). Yes, that is a trend toward better outcomes, but it is not proof of a lack of harm. We can harm patients by giving epinephrine to patients who would otherwise be resuscitated with less neurological deficits – if the epinephrine in causing neurological deficits. This neurological harm is certainly biologically plausible. We can harm patients by giving epinephrine to patients who would otherwise be resuscitated – if the epinephrine in causing decreased survival. This decreased survival is certainly biologically plausible. We know that… Read more »
Rogue, love your fighting spirit! folks, We just did an interview about this and hope to get it out soon as the next prehospital podcast! Certainly its a stalemate in my view. Yes we can harm with epi. nothing is benign. its all in the timing and the dose! We dont know yet is what it boils down to. But if you are doing good CPR, got the airway sorted, are having a good eTCO2 trace and there is refractory VF arrest, what choice do you have when all your other therapies have failed? Do you call it a day,… Read more »
Minh Le Cong, I apologize for the length of this, but . . . If Xigris were cheap, would that change anything? The cost, or age, of the drug is not important in determining if the drug works. We expect the patient to end up with much larger medical bills when epinephrine is given, than when epinephrine is not given. The cost of the epinephrine is not what is expensive. The resultant ICU stay is what is expensive. We need a study comparing the patients who do receive epinephrine vs. patients who receive a placebo. Then we will know how… Read more »
Hey Rogue love the response! no need to apologise. this is how we improve what we do! passion for excellence. PACA is our best available evidence to date. it was a placebo controlled trial so compared epi to homeopathic salty water. no increased harm was demonstrated. but increased ROSC for whatever worth you might want to credit that. Agree Another trial is helpful . disagree we need to change international guidelines at this point. Take the ResQPod and ITD debate. One trial is suggestive of benefit but I have not gone out and bought my pair and changed my practice… Read more »
Minh Le Cong, disagree we need to change international guidelines at this point. We should not be evidence based zealots in clinical medicine and health care. Where definitive evidence is lacking or incomplete we still need to make a clinical opinion based decision. While not all treatment requires evidence of improved survival, I don’t think that we should be making treatments standards of care until after we have evidence of improved survival, or similar appropriate endpoint. Epinephrine is the standard of care, so there has been opposition to depriving patients of the standard of care, because is is presumed that… Read more »
oh and by the way, leave my rubber chicken out of this! lol
For those who do not understand the rubber chicken reference –
http://resusme.em.extrememember.com/?p=5608
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Everybody knows that a rubber chicken without a pulley in the middle is useless!
okay Rogue
Your baseball analogies kick ass..much better than mine. I concede on that front!
There is no evidence that adrenaline or intubation in cardiac arrest are helpful and evidence they are more than likely of harm. There is evidence adrenaline increases ROSC but not survival to neurologically intact discharge from hospital (1, 2) but rather the opposite (3). ROSC by itself doesn’t mean anything and is not a metric by which to measure “success” in cardiac arrest resuscitation. It’s quite equivalent to winning the battle but loosing the war. There is evidence intubation attempts interrupt CPR (4) and counter-evidence showing high quality, minimally interrupted CPR improves survival to hospital discharge (5). Additional evidence shows… Read more »
Hello Scott & your group of active debaters. I’m relatively new as a listener to EMCrit – and I think this “Wee” (perhaps the biggest discussion ever from a small “Wee”) was posted after I began responding to your podcasts. I’ve “met” Rogue Medic (long back-and-forth with him and myself on his blog with the only conclusion from that the certainty that he and I will both respectfully agree to disagree). Anyway- My reply will be short because I wrote it all up in detailed on my ACLS COMMENTS- Issue #10 (https://www.kg-ekgpress.com/acls_comments-_issue_10/ ). To my reading – the studies being… Read more »
Further to what I wrote above, there is no evidence showing that placement of an advanced airway improves neurologically intact survival in patients who suffer a cardiac arrest and evidence showing no difference in survival between intubation and the LMA; see (6) above. There is also evidence showing that delayed ventilation and avoidance of hyperventilation improve neurogenic outcomes in cardiac arrest patient (7, 8) I know I’m getting a little away from the subject of adrenaline but that (along with shoving an endotracheal tube down the patients gob) is nothing more than tradition and superstition wrapped up in physiologic theory… Read more »
thanks Ben. that is useful. I would suggest caution in assuming cardiac arrest is one entity with one pathhysiology. Reversible causes of arrest do occur and may not respond to purely chest compressions and defibrillation. no one has done a randomised controlled trial of giving potassium in hypokalaemic arrest but I suspect our peers would consider that a reasonable decision despite lack of controlled evidence in the event of refractory arrest not responding to initial measures. and no one has done a long term hospital discharge survival study on treating hyperkalaemic arrest with calcium yet our peers would consider that… Read more »
Just to throw more wrenches in the works, the AHA has removed potassium supplementation during arrest from the recs for hypokalemic arrest if I remember correctly.
when dont you remember anything correctly, Scott!
this is the reference
http://circ.ahajournals.org/content/122/18_suppl_3/S829.full
read carefully! it advises against empiric bolus admin of KCL in suspected hypokalaemic arrest. Logical, totally. My suggestion is that in known hypokalaemic arrest ..someone intubated and ventilated, being transported IHT , you do an iSTAT for lytes, woah K is 1.5,they go into torsades arrest…we are not going to just do CPR and defib are we?
does the fact we have no controlled data for long term survival stop us from giving a drug that is biologically plausible to improve ROSC?
Minh, I would suggest caution in assuming cardiac arrest is one entity with one pathhysiology. One of my objections to the routine use of epinephrine in cardiac arrest is that it is treating cardiac arrest as if it is one entity with one pathhysiology. Everybody dead gets epi! The exception is those who are resuscitated before epinephrine can be given. Where is the attempt to avoid treating the cardiac arrests due to MI? Heart attack is supposed to be the most common cause of cardiac arrest. Epinephrine may be the worst legal drug we could give to a heart attack… Read more »
I think we found another point of agreement! Yes , there should be no routine use of epi in cardiac arrest.
ACLS Modifications in Management of Severe Cardiotoxicity Due to Hypokalemia Life-threatening hypokalemia is uncommon but can occur in the setting of gastrointestinal and renal losses and is associated with hypomagnesemia. Severe hypokalemia will alter cardiac tissue excitability and conduction. Hypokalemia can produce ECG changes such as U waves, T-wave flattening, and arrhythmias (especially if the patient is taking digoxin), particularly ventricular arrhythmias,205,206 which, if left untreated, deteriorate to PEA or asystole. Several studies reported an association with hypokalemia and development of ventricular fibrillation,207–210 whereas a single animal study reported that hypokalemia lowered the ventricular fibrillation threshold.211 However, the management of… Read more »
thanks, my friend
Tim, you are slick! must have been typing at same time as me!
Minh,
I type slowly and clumsily.
There is a good review of this question here –
Dissecting the ACLS Guidelines on Cardiac Arrest from Toxic Ingestions
Emergency Medicine News:
October 2011 – Volume 33 – Issue 10 – pp 16-18
doi: 10.1097/01.EEM.0000406945.05619.ca
InFocus
Roberts, James R. MD
http://journals.lww.com/em-news/Fulltext/2011/10000/InFocus__Dissecting_the_ACLS_Guidelines_on_Cardiac.7.aspx
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lets try a thought experiment. The President of the USA drops with a VF arrest right in front of you during an election rally to EMS and ED critical care providers(he was promising a major boost to funding for EMS and providing more ED critical care beds with shiny new vents for each bed) This is possibly the best chance the President has to survive his VF arrest, being in a roomful of emergency folk with all their gear (which was available to show to the President) The Secret service staff demand you assist before more help arrives. You start… Read more »
Minh, That is an interesting situation. I have debated this with Dr. Ken Grauer. He thinks that the reason that epinephrine may produce bad outcomes is that it is not given early enough. If I understand his position, it would be the earliest that epinephrine/adrenaline could be given that would be most likely to improve the outcome. I do not get to make these decisions, since I am a paramedic. I need to follow my protocols, which state to give epinephrine following defibrillation with no ROSC. I would prefer to work on improving the quality of the CPR, but that… Read more »
humor should never interfere with resuscitation
It is often a tough room to work.
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God all this new high tech medicine is so complex I say we go back to the days when whatever was wrong with the patient was hacked off with a rusty saw by a bootleg surgeon in his street clothes then the wound was cauterised in boiling oil and the patient quickly died from either hypovolaemia or infection; Pare, Semmelweis and Baron Lister be damned! (oh and adrenaline too right?) Cardiac arrest has multiple aetiologies I will not dispute that; but for a standard primary cardiac arrest I wouldn’t give adrenaline, I wouldn’t intubate the patient prior to ROSC and… Read more »
thanks Ben. I dont understand why you say you would still give amiodarone because its in the guidelines, yet you would not give adrenaline, which is still in all the international , including NZ, resuscitation guidelines? Was that a mistype on your part?
aMiodarone has never been shown to improve survival to hospital discharge from OHCA.
I agree, Ben. Adrenaline in myocardial infarction is not a decision to be taken lightly! But we are not talking about the same situation, are we? We are talking about OHCA, usually from MI but not always. These patients are dead, no pulse, no signs of life. The heart has stopped pumping blood. Technically its a reversible cause , MI causing arrest. If you can clear the thrombus and reperfuse the heart then might get it going again. The point is if you dont get the heart going again or provide alternative means of perfusing the brain and organs, then… Read more »
What are you views in regards of vasopressin ?
I don’t think vasopressin (ADH) has any advantage over adrenaline biologically and my brief search of the evidence seems to support this (9,10). I initially thought it not beyond the realms of biologic possibility that if adrenaline has harmful effects on the heart through beta stimulation increasing myocardial workload and oxygen consumption then as V1/V2 agonist vasopressin may not have this same effect as it is not stimulating these receptors. I am most likely however not correct. (9) Volker Wenzel, M.D., Anette C. Krismer, M.D., H. Richard Arntz, M.D., Helmut Sitter, Ph.D., Karl H. Stadlbauer, M.D., and Karl H. Lindner,… Read more »
How would you monitor bp in full cardiac arrest, especially in prehospital
Not sure I follow your logic sir?
Dr. Weingart has suggested using an arterial line to monitor pressure to guide decisions about when to use epinephrine. Not likely to be used in prehospital arrests, but the measuring CO2 does give feedback on the quality of compressions.
https://emcrit.org/podcasts/acls-guidelines-2010/
From about 11 1/2 minutes to 16 1/2 minutes he explains.
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Interesting. The Queensland Ambulance Service uses ETCO2 on an LMA as part of its cardiac arrest regime, it has been suggested here but was not introduced for a number of reasons. Such a technique has also been standard in the operating theatre for many-a-year. Recently the Ambulance Service here introduced a small pocket-sized CPR feedback device not unlike the QCPR feature of the MRx monitor a few of which were purchased here but I hear that the decision has since been made to return to Physiocontrol. http://www.stuff.co.nz/auckland/local-news/northland/whangarei-leader/6323099/St-John-tests-CPR-card
Let us assume that a 10% improvement in survival to discharge is significant. How big a study would you need to show this occurs with adrenaline (acknowledging the great heterogeneity of OHCA patients)? Has that study been done? And if that study has not been done, what end-points should we use instead to evaluate its effectiveness?
Interesting that both the PACA and JAMA studies have one of the lowest reported OHCA modern survival figures (105) and less asystolic rhythms.
http://www.alfredicu.org.au/assets/Documents/Reserach-Docs/Full-Publications/1-s2.0-S0300957211005715-main.pdf
Could it be possible that you aren’t going to show many intervention will benefit (including adrenaline) if you are predominantly treating dead people?
The VF/VT subgroup had better odds with adrenaline but CI too wide (probably due to lack of power in the analysis).
Maybe the lesson here is adrenaline is for resuscitation – not reanimation.
Edit above:
Interestingly that both the PACA and JAMA studies have one of the lowest reported OHCA modern survival figures (10%) and higher proportion of non-shockable (especially asystolic rhythms) compared to another recently published paper;
http://www.alfredicu.org.au/assets/Documents/Reserach-Docs/Full-Publications/1-s2.0-S0300957211005715-main.pdf
which had survival figures of > 10%.
Could it be possible that you aren’t going to show many intervention will benefit (including adrenaline) if you are predominantly treating dead people?
The VF/VT subgroup had better odds with adrenaline but CI too wide (probably due to lack of power in the analysis).
Maybe the lesson here is adrenaline is for resuscitation – not reanimation.
Great point! Though the French use the two terms as synonyms.
I am currently an MS-4 and going to be starting my EM residency at Yale in June. I’ve been listening to these pod casts and think they are amazing! Quick question about the practicalities of designing an RCT to study this question. The one thing that jumps out in my mind is how would you even consent subjects? I would think that this would be especially challenging as this study is challenging such a (for better or for worse) time-honored standard of care. I feel like I might be ignorant of some way around this issue so any help with… Read more »
It was all set up in Australia includind consent, waivers, IRB, etc. Then the EMS services that agreed to participate pulled out and the study became under-powered. I would say a trial like this could easily pass IRB. All of the trials have been negative to date, yet people are still doing it. This defines equipoise.