Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

Answer to What is this Treatment and Why Did We Stop Using it

Earlier I wrote What is this Treatment and Why Did We Stop Using it. The first answer, from Dewayne, was the correct answer.

Recent studies suggest that epinephrine doses up to 10 times larger than this produce improved coronary and cerebral hemodynamics and defibrillation rates in animals2,3 and humans.4 Small case series in humans have also suggested that these larger doses given very late in cardiac arrest were more effective in producing initial return of spontaneous circulation, but not in aiding survival.5,6 Clinicians are already using these doses, which equal approximately 15 mg in an adult, despite the absence of better proof of their effectiveness.7-9 [1]

Dewayne wrote –

Sounds like High Dose Epi.

A little later, kindofafireguy wrote –

I agree – sounds like high dose epi. We still give epi for cardiac arrest despite the lack of solid evidence that it improves outcomes.

That is my point in posting about these treatments that we stopped using. We use plenty of treatments without any good evidence – no better than the treatments that we admit are failures.

We need to finally admit that a lot of the treatments we are still using are also failures.


Click on images to make them larger.

This is comparing three different treatments HDE (High-Dose Epinephrine), SDE (Standard-Dose Epinephrine), and NE (NorEpinephrine). The lines for the HDE and NE are so close to each other, that you may not be able to see the gold line.

We stopped using High-Dose Epinephrine because of this study and at least one other study that had similar outcomes.[2] Most of us in EMS probably never even used NorEpinephrine.

Why?

The drugs did not improve outcomes.

There was no good reason to give a drug that did not improve outcomes – as long as we were giving some drug – because we have to feel as if we are making a difference.

We probably are making a difference. We are probably making things worse.

Compare that chart of HDE, SDE, and NE with this chart comparing Epinephrine and No Epinephrine.[3]

Are there any important differences?

No.

We eliminated the treatment that improved ROSC, but did not improve survival and did not improve neurological function – as long as we could give some drug – but we won’t get rid of a treatment that is just as useless when it means that the ALS people will not have a drug to give.

The drug does not work.

The drug may make things worse.

The drug does not make things better.

There is no good reason to continue giving epinephrine outside of randomized controlled trials.

All things are poison and nothing is without poison, only the dose permits something not to be poisonous. – Paracelsus.

We do not appear to have lowered the dose enough for epinephrine to be safe. We don’t know what that dose is and we never will know if we continue to give epinephrine without demanding randomized controlled trials.

Footnotes:

[1] A randomized clinical trial of high-dose epinephrine and norepinephrine vs standard-dose epinephrine in prehospital cardiac arrest.
Callaham M, Madsen CD, Barton CW, Saunders CE, Pointer J.
JAMA. 1992 Nov 18;268(19):2667-72.
PMID: 1433686 [PubMed – indexed for MEDLINE]

[2] A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. European Epinephrine Study Group.
Gueugniaud PY, Mols P, Goldstein P, Pham E, Dubien PY, Deweerdt C, Vergnion M, Petit P, Carli P.
N Engl J Med. 1998 Nov 26;339(22):1595-601.
PMID: 9828247 [PubMed – indexed for MEDLINE]

Free Full Text From NEJM

[3] Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest.
Hagihara A, Hasegawa M, Abe T, Nagata T, Wakata Y, Miyazaki S.
JAMA. 2012 Mar 21;307(11):1161-8. doi: 10.1001/jama.2012.294.
PMID: 22436956 [PubMed – indexed for MEDLINE]

Free Full Text from JAMA.

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Comments

  1. Rogue, I have a question for you. I’ve heard it suggested that one possible factor in the lack of positive outcomes is the fact that the majority of cases in non-shockable rhythms (and therefore basically reliant on drug therapy such as HDE) have gone outside the range of effective resuscitation. Therefore, this would contribute to some of the negative statistics for HDE. What are your thoughts on this theory?

    I’m just curious to hear your take on this. I personally agree that HDE is more dangerous than helpful, but a medic I work with thinks that in the lack of anything better, it’s the lesser of two evils. I’m not sure if that is because he honestly believes it, or if it’s just a case of “that’s the way we’ve always done it.”

    • kindofafireguy,

      Rogue, I have a question for you. I’ve heard it suggested that one possible factor in the lack of positive outcomes is the fact that the majority of cases in non-shockable rhythms (and therefore basically reliant on drug therapy such as HDE) have gone outside the range of effective resuscitation. Therefore, this would contribute to some of the negative statistics for HDE. What are your thoughts on this theory?

      That could be true.

      If we want to find out, we need a randomized placebo-controlled study.

      Without that, all we are doing is guessing about what the results would be. Nobody knows.

      I’m just curious to hear your take on this. I personally agree that HDE is more dangerous than helpful, but a medic I work with thinks that in the lack of anything better, it’s the lesser of two evils. I’m not sure if that is because he honestly believes it, or if it’s just a case of “that’s the way we’ve always done it.”

      There are many possible treatments (evils).

      I do not see any reason to choose any treatment that does not have evidence of producing good outcomes.

      Only chest compressions and defibrillation have that kind of evidence.

      If there were valid evidence for improved survival with any kind of use of epinephrine, then this kind of controversy would not happen.

      Itt is because we have a treatment that was made the standard of care before there was evidence to justify making epinephrine a standard of care. We have this problem with many other treatments, which makes it difficult to not harm patients.

      First, do no harm – unless the harm is to comply with the Standard Of Care.

      This is bad medicine.

      .

      • Agreed. Unfortunately, due to the “sue first, ask later” nature of society in the United States today, I honestly doubt we’ll see these sorts of studies any time soon. It would require someone stepping up and going against the “standard of care” (which, honestly, is really often a lack-thereof). I would be interested to see the results of such a study though.

        • kindofafireguy,

          Agreed. Unfortunately, due to the “sue first, ask later” nature of society in the United States today, I honestly doubt we’ll see these sorts of studies any time soon. It would require someone stepping up and going against the “standard of care” (which, honestly, is really often a lack-thereof). I would be interested to see the results of such a study though.

          Dr. Callaway stated in his editorial –

          Thus, properly evaluating this traditional therapy now seems necessary and timely and should consist of a rigorously conducted and adequately powered clinical trial comparing epinephrine with placebo during cardiac arrest. Such a trial has previously seemed unethical, and investigators who have attempted to perform this comparison have received unwarranted criticism in their communities. 17,19 While awaiting results of such a definitive trial, physicians and other practitioners involved in cardiac resuscitation must consider carefully whether continued use of epinephrine is justified.

          This appears to make it just as likely that we could be sued successfully for giving epinephrine as for not giving epinephrine.

          Since Dr. Callaway is one of the doctors who writes the ACLS Guidelines, I think that we can expect epinephrine to be de-emphasized in the next revision of the ACLS Guidelines. It could be moved from Class IIb (there might be a benefit) to Class III (the risk is greater than the benefit).

          .

  2. Like all EMS agencies, we follow the standard ACLS algorithm for cardiac arrests & out of 5 years worth of many arrests, I’ve only gotten 3 back to where they walked out neurologically intact; but when i started, my agency had just recently yanked the MDV of HDE & went w/ prefilled 1:10 q3-5m. We also use Vasopressin as our 1st or 2nd. We use Amio in V-arrests (no Lido anymore) & MGSO4 in refractory VF. I had to learn it in medic school but have yet to hear any local agencies using it: Bretylium. I hear from a lot of old school medics that it was a great arrest medication but when i asked why we don’t use it, my instructors all said that the warehouse that manufactured it, burnt down & no more was made. Here I’m allowed to take a 1mg amp of 1:1 & dilute in a 250mL NaCL & run in but again…never hear of many doing it. We run through our 6 boxes of 1:10 & others then call for termination orders.

    • 6 doses – is that an unspoken rule, or an actual policy? If it is an actual policy, I find that very interesting, and honestly probably helps with false hopes of effective resuscitation.

    • Medic Minx,

      Like all EMS agencies, we follow the standard ACLS algorithm for cardiac arrests & out of 5 years worth of many arrests, I’ve only gotten 3 back to where they walked out neurologically intact;

      It would be a mistake for us to blame our good outcomes, or our lack of good outcomes on the limited number of patients in our anecdotal experience. This is why we need to require large studies to find out what actually works.

      but when i started, my agency had just recently yanked the MDV of HDE & went w/ prefilled 1:10 q3-5m. We also use Vasopressin as our 1st or 2nd. We use Amio in V-arrests (no Lido anymore) & MGSO4 in refractory VF. I had to learn it in medic school but have yet to hear any local agencies using it:

      The research does not support routine use of magnesium for VF, but there is no evidence for any medication improving survival from VF.

      Bretylium. I hear from a lot of old school medics that it was a great arrest medication but when i asked why we don’t use it, my instructors all said that the warehouse that manufactured it, burnt down & no more was made.

      This is from the 2000 ACLS Guidelines –

      References to bretylium have been dropped from the ventricular fibrillation (VF)/pulseless VT algorithm. In 1998 through 2000, severe problems with obtaining the raw materials to produce bretylium stopped the supply for a number of months. These guidelines must avoid generating a demand that cannot be met by an undependable source. The world’s natural sources of bretylium appear to be nearly exhausted. Bretylium remains acceptable to use, but it is no longer recommended. Bretylium has a high incidence of side effects, particularly hypotension, in the postresuscitation setting. Bretylium stays as a Class IIb recommendation because no new, supportive information is available and some studies question its efficacy.

      Bretylium is not even mentioned in the 2005 ACLS Guidelines.

      A lot of people believe that there must be some magical treatment that will work and that we have to try something, regardless of how much harm it can cause.

      These people believe in voodoo, not medicine. Trying to understand why they believe in things without any valid evidence is a waste of time.

      Here I’m allowed to take a 1mg amp of 1:1 & dilute in a 250mL NaCL & run in but again…never hear of many doing it. We run through our 6 boxes of 1:10 & others then call for termination orders.

      We do not know if any dose of epinephrine might improve survival.

      The defenders of the status quo have prevented us from learning if epinephrine has any benefit.

      We have nobody to blame but ourselves. We put our faith in Standards Of Care and stopped providing good medical care.

      .