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

- Rogue Medic

Killing Patients Just to Get a Temporary Pulse With Epinephrine

Today in JAMA there is a non-randomized observational study of epinephrine vs. no medicine in 417,188 EMS cardiac arrest patients. I will be writing about this study in more detail, but I have already written a lot about the earlier studies that demonstrate the harm of epinephrine in cardiac arrest.

We never had a good reason to make epinephrine the standard of care in cardiac arrest.

 

Never.

 

The goal of resuscitation is NOT to get a pulse back.

But . . . but . . . but . . . if we don’t get pulses back, we can’t resuscitate patients.

Yes, but that does not mean that it does not matter how much harm we do in order to get pulses back.

Just because epinephrine increases the rate of return of pulses does not mean that epinephrine increases the rate of survival to discharge.

In the treatment of cardiac arrest, nothing is more important than survival to discharge.

OK, survival to one month is more important. Survival to one year is more important. Survival to ten years is more important.

A pulse for a few days is not important. A pulse for a few hours is not important. A pulse for a few minutes is not important. There is a word to describe these patients who never leave the hospital – dead.

only 1.4% of patients in the epinephrine group had good neurological outcomes, despite a 5.4% survivalrate (Table 1). Thus, only about 25% of survivors had good neurological outcomes.[1]

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 [2]

The only thing unethical has been the resistance from those defending the Standard Of Care, that was nothing more than a refusal to examine tradition.

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.[2]

How can we justify a treatment that has never been based on any study of survival? We do not have any good reason to expect that the results of a randomized placebo-controlled study will support continuing use of epinephrine.

Epinephrine should only be used in cardiac arrest as a part of controlled studies.

Expert recommendations must come with an expiration date.

 

No exceptions.

 

If the expert recommendation is not followed by appropriate research, then the expert recommendation should not be treated better than the patients.

ROSC (Return Of Spontaneous Circulation) is nice, but ROSC is only a surrogate endpoint. If we are creating a dangerous condition by transporting the patient to the hospital; if the patient never wakes up; if we create false hope for the family; if we generate huge bills that may bankrupt the family; if we takes hospital staff away from the treatment of other patients – where is the benefit?

But . . . but . . . but . . . the family will be able to say goodbye to their loved one while the person has a pulse.

Really?

How many millions of dollars is that worth to make us feel good, regardless of what the family wants?

Why do we assume that this is what the family wants? Do we ask? Of course not – we don’t want to risk learning the truth.








 

50 years of tradition, unimpeded by progress.

 

Forget it, Jake. It’s Chinatown.

 

There is also audio of an interview with Dr. Calloway, who wrote the accompanying editorial.

Thank you to William Toon, PhD. of the EMS EduCast for bringing this to my attention.

Footnotes:

[1] 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.

[2] Questioning the use of epinephrine to treat cardiac arrest.
Callaway CW.
JAMA. 2012 Mar 21;307(11):1198-200. doi: 10.1001/jama.2012.313. No abstract available.
PMID: 22436961 [PubMed – indexed for MEDLINE]

Link to a free 6 1/2 minute recording of an interview with Dr. Callaway about this paper.

On the right side of the page, to the right of the First Page Preview, is a section with the title Multimedia Related by Topic. Below that is Author Interview. Below that is some information about the edition, . . . , and below that is an embedded recording of the interview. Press on the arrow to play. That has the recording of the interview with Dr. Callaway.

This is definitely worth listening to.

.

Comments

  1. I have to admit I have always known that epi was the standard of care for cardiac arrests and yet there has never been any conclusive reason why. I am surprised to hear it is so detrimental to the patient’s overall outcome. In your research have any viable alternatives been presented?

    On a separate note I love the blog. Find it very informative and entertaining. Love the quotes. Especially the one about naloxonation. Keep up the good work, we’ll keep reading.

    • Romeo,

      I have to admit I have always known that epi was the standard of care for cardiac arrests and yet there has never been any conclusive reason why. I am surprised to hear it is so detrimental to the patient’s overall outcome. In your research have any viable alternatives been presented?

      Nitroglycerine, sodium nitroprusside, and adenosine are some of the drugs being studied.

      These may offer significant improvements over epinephrine, or with low-dose epinephrine, but they are working their way through the research process, rather than being implemented without good evidence.

      On a separate note I love the blog. Find it very informative and entertaining. Love the quotes. Especially the one about naloxonation. Keep up the good work, we’ll keep reading.

      Thank you.

      .

      • Nitroglycerine, sodium nitroprusside, and adenosine are some of the drugs being studied.

        “Really? Can’t imagine a reason for using vasodilators and adenosine during cardiac arrest. Where can I see those studies?

        • Gerardo Gastélum,

          Nitroglycerine, sodium nitroprusside, and adenosine are some of the drugs being studied.

          “Really? Can’t imagine a reason for using vasodilators and adenosine during cardiac arrest. Where can I see those studies?

          Too many people think that vasopressors are important, but there is no evidence that vasopressors have ever improved the survival of anyone from cardiac arrest.

          Sodium nitroprusside enhanced cardiopulmonary resuscitation (SNPeCPR) improves vital organ perfusion pressures and carotid blood flow in a porcine model of cardiac arrest.
          Schultz J, Segal N, Kolbeck J, McKnite S, Caldwell E, Yannopoulos D.
          Resuscitation. 2012 Mar;83(3):374-7. Epub 2011 Aug 22.
          PMID: 21864483 [PubMed – in process]

          Sodium nitroprusside enhanced cardiopulmonary resuscitation improves survival with good neurological function in a porcine model of prolonged cardiac arrest.
          Yannopoulos D, Matsuura T, Schultz J, Rudser K, Halperin HR, Lurie KG.
          Crit Care Med. 2011 Jun;39(6):1269-74.
          PMID: 21358401 [PubMed – indexed for MEDLINE]

          Sodium nitroprusside-enhanced cardiopulmonary resuscitation improves resuscitation rates after prolonged untreated cardiac arrest in two porcine models.
          Schultz JC, Segal N, Caldwell E, Kolbeck J, McKnite S, Lebedoff N, Zviman M, Aufderheide TP, Yannopoulos D.
          Crit Care Med. 2011 Dec;39(12):2705-10.
          PMID: 21725236 [PubMed – indexed for MEDLINE]

          Sodium nitroprusside enhanced cardiopulmonary resuscitation prevents post-resuscitation left ventricular dysfunction and improves 24-hour survival and neurological function in a porcine model of prolonged untreated ventricular fibrillation.
          Schultz J, Segal N, Kolbeck J, Caldwell E, Thorsgard M, McKnite S, Aufderheide TP, Lurie KG, Yannopoulos D.
          Resuscitation. 2011 Dec;82 Suppl 2:S35-40.
          PMID: 22208176 [PubMed – in process]

          High dose nitroglycerin treatment in a patient with cardiac arrest: a case report.
          Guglin M, Postler G.
          J Med Case Reports. 2009 Aug 10;3:8782.
          PMID: 19830240 [PubMed]

          Also listen to the following free podcast from EMCrit –

          EMCrit Podcast 69 – The Future of CPR with Keith Lurie and Demetris Yannopoulos
          by EMCRIT on March 19, 2012
          Page with links to the podcast and other sources of information

          There is no reason to believe that the way that epinephrine increases coronary circulation is good for the survival of the patient. Epinephrine has only been shown to improve ROSC, but even with all of those extra resuscitations, there has never been any evidence of improved survival past discharge.

          We do not know what is best, but because of our unreasonable confidence in epinephrine, we have been ignoring things that are not like epinephrine.

          How many people who could have been resuscitated with a good outcome if we had avoided epinephrine?

          We do not know.

          .

        • Dr. Weingart over at emcrit has had Drs. Lurie and Yannopoulos on discussing that strategy.

    • In my career I have had 21 cardiac arrest saves. 75% of them received EPI either IV or ET. There were no complications with the 1 ET dose. They are all to this day all alive and living well. Since we have switched to vaso as initial treatment I have had no saves. Really makes me wonder the situations they are using for these studies. The same with Lidocaine vs. Amiodarone. Saves with Lidocaine and not one with Amiodarone…well at least to be discharged and live a normal life.

      Then again, you have to remember to treat the problem because if you don’t you will never have a save!

      • Karen,

        That is why we use research, rather than anecdotes (such as the patients you, or anyone else remember) to determine what is good patient care.

        Anecdotes are not controlled for anything, while research provides clear information about what is controlled for.

        Anecdotes are also much more likely to be influenced by our memories, while research requires strict documentation to compare patients and to not rely on memory.

        .

  2. “If I give this table enough epinepherine I might get pulses back, but it will never again be a tree.”

  3. To talk about Epi as uniformly “causing harm” in cardiac arrest is jumping to conclusions about a non-randomized, observational study about which I really see no details from the JAMA abstract about the types of patients and additional key specifics that were involved. I do not have access to the complete article – I’m glad to review it if someone provides me with this (JAMA 307:1161-1168, 2012). Perhaps there is also an insightful Editorial?

    Observational studies are just that – observations – NOT proof. Based on observational studies done on large numbers of women we routinely treated with estrogen for many years – until controlled, prospective trials were done and showed the fallacy of that previously uniformly accepted observational dogma …

    There is a lot I don’t know about this Japanese study from reading the abstract. Patients had OHCA prior to EMS arrival. We don’t know the initial mechanism (rhythm) in the two groups (VT/VF? Asystole? PEA) – we don’t know the time the patient was down? How long until EMS was notified? arrived? percentage of patients with a ‘shockable rhythm’ ? relative percentages responding to shock? ie – What is the likelihood of being able to get patients back in BOTH of the groups? Were the groups otherwise equivalent?

    The Goal of Epi? – mainly to improve coronary flow during cardiac arrest and to increase the chances of ROSC with resuscitation including defibrillation. It won’t save the brain of a patient whose brain is already dead. It might enable some of those already brain-dead patients to attain ROSC – but that doesn’t mean Epi was the causative factor in such patients poor neurologic outcome. Perhaps the focus of research ought to be more into which patients should have resuscitation attempted – and which should not? (though that is a highly challenging issue – and even if one gets “data” – such data won’t exclude the possibility that some “outliers” might defy the odds and be resuscitated). And, given the worldwide increasing prevalence of PEA/Asystole as mechanisms of arrest – the chance for ultimate survival is far less than it used to be when primary VF was the major mechanism.

    It is incredibly difficult to perform randomized, controlled double-blinded clinical trials on cardiac arrest for obvious reasons. Focus of health care providers on-the-scene is on saving the patient – not prospectively randomizing victims to one or another group and protocol. All codes are unique (different). Granted – there is NO data proving the benefit of Epi (just like data is lacking for proving benefit of other interventions in true cardiac arrest). Lack of data doesn’t necessarily mean all use of Epi should stop (Controlled randomized trials on the benefits of a parachute for jumping out of an airplane are also lacking – though this doesn’t mean use of parachutes should be abandoned … ).

    The interpretation of “data” often depends on who and how that data is interpreted. The numbers regarding survival differences and differences in mental status between Epi and non-Epi groups are not marked to my reading of this JAMA abstract. They reach “statistical significance” because of the huge numbers of subjects in the study – but I don’t know that this constitutes “proof” of cause-and-effect given the lack of specifics on subjects in each of these non-randomized observational study groups. Perhaps the nonrandomized patients who didn’t get Epi yet still recovered portray a subset more likely not to have longterm residual neurologic impairment.

    There remains a LOT we don’t know about cardiac arrest. Overall chances that it will be the Epinephrine by itself that “saves” the patient in the setting of OHCA due to VF not immediately responding to defibrillation are very small indeed – if not downright tiny. Those observational patients who were in VF and responded right away to defibrillation (perhaps BEFORE there was even a chance to give Epi) – are clearly far more likely to have longterm survival and far better neurologic status (since such patients almost certainly were gotten to in LESS time than the other group … ). So it would see that non-Epi patients in this observational study have a reason to do better!

    BOTTOM LINE: I’m open to reviewing the entire manuscript – but from the JAMA abstract I find it hard to conceive that this article will do anything beyond adding confusion to the ever challenging problem of optimizing survival and outcome from cardiac arrest.

    • Excellent summation. Thank you for saying what I was thinking as I read this.

    • Thank you! I totally agree with you. Why is it that something that is from nature is not good because they don’t know why it works, “it just works”.

      I think there is a time and a place for EPI. I must say I have personally had 21 cardiac arrest “true” saves in my career at this point. I have used EPI IV and ET tube with no complications. Yes, I mean walk out of the hospital saves. I would say at least 75% had at least one dose of EPI. I will take an awful lot to change my mind.

      Don’t even get me started on lidocaine vs amiodarone!!

      • Karen,

        Thank you! I totally agree with you. Why is it that something that is from nature is not good because they don’t know why it works, “it just works”.

        A great way to convince me that you do not understand medicine is to suggest that because something is natural, it is somehow better for patients than something artificial. Cyanide is all natural. Botulism is all natural. Anthrax is all natural. Bubonic plague is all natural.

        If you haven’t noticed, nature does a great job of killing people. Medicine is the most important part of what has increased the life expectancy from 49.24 years at the turn of the 20th Century to 76.83 years at the turn of the 21st Century. Almost every species that ever lived is extinct. Nature is trying to kill us, but science is keeping us alive for longer lives of higher quality.

        Every time a life is saved, we are giving nature the finger. Nature kills.

        I think there is a time and a place for EPI. I must say I have personally had 21 cardiac arrest “true” saves in my career at this point.

        Please provide the documentation.

        I have used EPI IV and ET tube with no complications.

        How do you know that there were no complications?

        Again, please provide the documentation.

        You do realize that pushing drugs down the tube is no longer recommended. This is another thing that was recommended without any evidence of any benefit.

        This observational study is able to provide information in answer to my questions, because they did actually observe and record what they were doing. That information, and more, is the basis for this study. You don’t like this research, but want us to accept your war stories.

        Yes, I mean walk out of the hospital saves. I would say at least 75% had at least one dose of EPI.

        You don’t even know how many patients you gave epinephrine to.

        15,030 patients received epinephrine in the study – not approximately, but exactly. But you think that your recollection is somehow more accurate than what was documented.

        This is why research is important – memory is not even close to reliable, or accurate.

        I will take an awful lot to change my mind.

        You appear to be a true believer. True believers see what they believe, regardless of what is in front of them.

        Don’t even get me started on lidocaine vs amiodarone!!

        Why not?

        Neither one does anything good for cardiac arrest patients.

        Where are the outcomes studies that Wyeth promised us? Were the results that bad, that they had to be hidden?

        How many more of your patients would have survived to be walking around if you did not use epinephrine?

        Why do you want to use a drug that has only been shown to harm patients when we look at the one outcome that matters? That outcome is survival beyond discharge with good neurological function.

        .

        • I haven’t had as many saves as Karen has, I’ve only had 4 throughout my 7 years as a medic. However, 3 out of the 4 received Epi and 1 of those 3 received it down the tube because she had no vascular access and we didn’t carry the EZ-IO at the time. All 4 of my saves have survived to discharge with no neurological deficits and came to our station to thank us for saving them. The 4th one was a STEMI that we saw go into R on T and drop into VT and was immediately welded and as my partner started compressions the pt opened his eyes and started talking to us.

          The thing is most of the codes we encounter have been down an unknown length of time, so by the time that we get to them they are already pretty much brain dead from lack of oxygenation. How are we to know if the Epi is the culprit. I do however agree that if you give enough of an vasopressor you’ll likely get a pulse out of it, especially with Levophed, that crap would give a pulse to someone who’s been dead for a week.

          I would like to see more of a controlled study done on the effects of Epi and the neurological deficits it creates. I however think it would be difficult to get someone to voluntarily die so they can see if it really works or not.

          • Joe,

            We do not need to have anyone volunteer to die in order to study epinephrine. People have about 1,000 cardiac arrests a day.

            We just need to study the results of giving epinephrine vs. not giving epinephrine.

            If we do not do that, we are experimenting on everyone with a drug that has a lot of evidence of harm and no evidence of improved survival.

            We need to know what works, not what voodoo makes the medics, nurses, and doctors feel like they are making a difference.

            .

    • Dr. Grauer,

      My response to part of your comment is in Dr. Ken Grauer on Killing Patients Just to Get a Temporary Pulse With Epinephrine – Part I. I will be addressing your points a little at a time.

      .

  4. I totally agree with outcome based study’s. And I believe we need to examine everything.
    BUT PLEASE guys, We have to stop accepting responsibility for the cost of healthcare. Did we buy that morphine for 1.50 then charge 150?
    It is neither our fault, nor within our power to change what a hospital charges.
    I WILL NOT base my medical decisions on possible future costs!!!

    • Mike,

      I totally agree with outcome based study’s. And I believe we need to examine everything.

      Thank you.

      BUT PLEASE guys, We have to stop accepting responsibility for the cost of healthcare. Did we buy that morphine for 1.50 then charge 150?
      It is neither our fault, nor within our power to change what a hospital charges.
      I WILL NOT base my medical decisions on possible future costs!!!

      If the cost of medication is not raised, it will only be something else. I don’t know what a fair cost is, but we do have a problem with the cost of health care.

      .

  5. The thinking on this is just wrong on so many levels that I just can’t wrap my head around any “science” that may be involved. First, I didn’t see anything in this article that tells me a physiological reason to NOT use epi. I see statistics (and may I borrow a phrase here, “There are lies, there are damned lies, and then there are statistics.”) which state that epinephrine does not improve survival to discharge. But if they don’t survive to get definitive care wouldn’t that skew the numbers just a teeny weeny bit? “ROSC (Return Of Spontaneous Circulation) is nice, but ROSC is only a surrogate endpoint.” without ROSC you just don’t have much chance for anything else do you?!

    Dr. Grauer, well said. Thank you for being a voice of reason.

    Oh, and one more thing…. “How many millions of dollars is that worth to make us feel good, regardless of what the family wants?” My question would be, “How many millions of dollars is it worth to have a patient WALK out of the hospital doors?”

    • Sara Mink-Taylor,

      The thinking on this is just wrong on so many levels that I just can’t wrap my head around any “science” that may be involved.

      Then please explain what science is behind giving patients a drug that has absolutely no evidence of improved outcomes – ever.

      First, I didn’t see anything in this article that tells me a physiological reason to NOT use epi.

      That is not the purpose of research. That is just the analysis of research and it is usually wrong. If it were right, we should be able to improve survival with epinephrine, but we can’t.

      I see statistics (and may I borrow a phrase here, “There are lies, there are damned lies, and then there are statistics.”) which state that epinephrine does not improve survival to discharge.

      OK. You don’t understand science and you don’t understand statistics. You are definitely not the person to give advice on anything here.

      But if they don’t survive to get definitive care wouldn’t that skew the numbers just a teeny weeny bit?

      “ROSC (Return Of Spontaneous Circulation) is nice, but ROSC is only a surrogate endpoint.”

      without ROSC you just don’t have much chance for anything else do you?!

      Just because ROSC is important at some point does not mean that it does not matter how you get ROSC.

      We need to stop killing patients, just because epinephrine is the easiest way we know to get ROSC.

      Dr. Grauer, well said. Thank you for being a voice of reason.

      Oh, and one more thing….

      “How many millions of dollars is that worth to make us feel good, regardless of what the family wants?”

      My question would be, “How many millions of dollars is it worth to have a patient WALK out of the hospital doors?”

      I would not put a price on that.

      I am just trying to point out that YOU are the one stopping the patients from walking out the door by using epinephrine.

      Stop killing patients with epinephrine. Stick to less harmful treatments.

      .

  6. Rogue Medic was kind enough to provide me with copies of the JAMA article and accompanying Editorial by Callaway which I have reviewed in some detail.

    My question: What is the chance of survival using ANY means for a group of patients when it takes an average of more than 7 minutes for arrival-on-the-scene (after the call to EMS has been made) – with well under half of the patients receiving no bystander CPR – such that 86-92% of patients are in PEA/Asystole on EMS arrival? Such is the setting for this study by Hagihara et al (Table 1- pg 1163). NOTHING is likely to work in such a subset of patients – and obvious that Epi (which significantly increases ROSC) will be likely to disproportionately worsen CNS outcome in such individuals (because many of these patients are already brain dead – and Epi is better than placebo at attaining ROSC in such subjects). Despite that – the percentage differences between Epi- and non-Epi groups for survival, CPC & OPC (neuro function, overall performance) are minimal – and I suggest not clinically important (with “statistical significance” only being reached due to large numbers of subjects in the study).

    I am not a statistician – and I admit to not understanding much of the technical jargon in the methodological portions of this manuscript – BUT – the cited “propensity score” data for Epi administration to my reading seems highly contrived – and I have trouble accepting this concept as being valid in this nonrandomized observational study …

    Thus – to my reading – this study tells us NOTHING new. We have long known that there are no studies proving survival benefit from Epi use in cardiac arrest. The overwhelming majority of patients who do survive OHCA have VF – short times from collapse to call for EMS – and prompt defibrillation without excessive additional underlying comorbidities. Lack of bystander CPR – delayed response times – initial rhythm being Asystole/PEA predispose to terrible outcome regardless of therapy. This study proves what we knew – namely, that Epi CAN increase ROSC, even in such patients. It is not in the least surprising that these ROSC subjects had poor neurologic outcome. I see no evidence from this study of a cause-and-effect relationship from use of Epi. Instead – one has to wonder IF Epi should be used in patients with minimal-to-negligible chance for recovery – BUT – until we can reliably determine the minority who might still be saved with intact neurologic function IF Epi is used – the decision of whether or not to give this drug remains problematic.

    I applaud the determination to design truly randomized, prospective clinical trials on the issue of Epi use in cardiac arrest. This will be a true challenge to accomplish. In the meantime – We are faced with having NO data on whether potential harmful effect (either from Epi itself- or from resuscitating patients who are already brain-dead) outweighs potential benefit from improving the chances of ROSC. In my opinion – until we know, Epi should continue to be used.

    • Dr. Grauer, can´t be more glad that U could explain (in a very simple and yet concise way) this to all of us…. From the begining my gut told me we shouldn’t start throwing out epi from our red boxes, but I did not have the wisdom and experience to put reasons (mine and science’s) in black and white.

      • Gerardo Gastélum,

        Dr. Grauer, can´t be more glad that U could explain (in a very simple and yet concise way) this to all of us…. From the begining my gut told me we shouldn’t start throwing out epi from our red boxes, but I did not have the wisdom and experience to put reasons (mine and science’s) in black and white.

        We never should have put epinephrine in our drug boxes without evidence that it improves outcomes, unless we also insisted on research to demonstrate if epinephrine actually does work.

        We never had that research.

        Nobody wants to know that if epinephrine works.

        everybody just wants to believe that epinephrine works,k because we want it to work.

        That is not medicine. That is alternative medicine.

        As Dr. Callaway stated –

        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.

        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.

        Where is the evidence to justify the use of epinephrine in cardiac arrest?

        .

        • Rouge Medic, You sound quite a bit like a fanatic. You have no evidence to stop the use of epi, yet insist that it be removed from the treatment of cardiac arrest. Tell me, what is the difference between no evidence that it helps, and no evidence that it hurts? You are insisting that epi causes harm with no evidence proving that statement. What you are doing is exactly what you claim everyone who disagrees with you is doing, throwing the scientific method out and just going with your gut.

          • David Wate,

            Rouge Medic, You sound quite a bit like a fanatic. You have no evidence to stop the use of epi, yet insist that it be removed from the treatment of cardiac arrest. Tell me, what is the difference between no evidence that it helps, and no evidence that it hurts? You are insisting that epi causes harm with no evidence proving that statement. What you are doing is exactly what you claim everyone who disagrees with you is doing, throwing the scientific method out and just going with your gut.

            The scientific method means requiring evidence of benefit before making something standard of care/standard of abuse.

            Treatments that are used without evidence can be just as easily dismissed without evidence.

            There is no contradiction.

            When treating patients, we need evidence that what we are doing to them is not making things worse – otherwise we are just practicing voodoo.

            .

            • Why don’t we discontinue other drugs too then like aspirin and heparin even integrellin

              How about Penicillin

              While we are at it lets get rid of digoxin or at least force the patients to go to the doctor to get it every day.
              Tikosyn is another dangerous one lets get rid of it.

              My point is many of these drugs WOULD NOT be approved by the FDA if petitioned today- these drugs have all been found to be dangerous even deadly even when used correctly.

              Modern medicine is based around speculation, ACLS is “best practices” meaning they try something and see how it works based on general statistics and tweak it every 2 years and see how it rolls

              By saying epi should be discontinued in ALL Cardiac arrest events is like telling a patient with a 95% occlusion “protocol says to give you blood thinners but we won’t because it may cause other smaller problems”

              • James stafford,

                Some of those treatments have clear survival benefits, but epinephrine does not improve survival.

                Do you understand that difference?

                For example, aspirin does kill hundreds of people, but aspirin prevents thousands of deaths.

                In the treatment of cardiac arrest, epinephrine does not save any lives, but epinephrine probably prevents lives from being saved.

                You must provide evidence of improved survival from epinephrine in cardiac arrest for your analogy to work.

                50 years of traditional use of epinephrine, unimpeded by a lack of evidence.

                Please provide some evidence that epinephrine improves survival from cardiac arrest.

                Your analogy is faulty. You claim that there is some kind of benefit to be considered in a risk/benefit analysis.

                There is no evidence of any survival benefit with epinephrine – none.

                Therefore, there is not enough benefit to balance the risks. After 50 years of use, somebody should be able to show some kind of survival benefit, but we cannot.

                Epinephrine should be limited to randomized controlled trials until we have evidence of benefit.

                .

    • Dr. Grauer,

      My second response to part of your comment is in Dr. Ken Grauer on Killing Patients Just to Get a Temporary Pulse With Epinephrine – Part II. I will be addressing your points a little at a time.

      .

  7. I have to say that for the last couple of hours i have been hooked by the impressive articles on this website. Keep up the wonderful work.

  8. Dr. Grauer, couldn’t agree with you more. After reading everything on here, Rogue, you seem extremely defensive and attacking other people’s comments. But not once have you replied to the good Dr. I think you may, just maybe talking out of your ass to start arguments and poke at people that think differently then you. There is no room for eliteist like you in the profession. So instead of telling us not to kill patients with Epi, how about YOU give YOUR patients a chance with it.

    • Fanatics, great,

      Dr. Grauer, couldn’t agree with you more. After reading everything on here, Rogue, you seem extremely defensive and attacking other people’s comments. But not once have you replied to the good Dr. I think you may, just maybe talking out of your ass to start arguments and poke at people that think differently then you.

      I have posted some of my responses to Dr. Grauer’s comments. I will post more. Your apparently willful blindness does not indicate any failure on my part.

      Rogue Medic says:
      Thu, 22 Mar 2012 16:38:33 +0000 at Thu, 22 Mar 2012 16:38:33 +0000 • Edit
      Dr. Grauer,

      My response to part of your comment is in Dr. Ken Grauer on Killing Patients Just to Get a Temporary Pulse With Epinephrine – Part I. I will be addressing your points a little at a time.

      .

      Here are the links to the responses already posted –

      Dr. Ken Grauer on Killing Patients Just to Get a Temporary Pulse With Epinephrine – Part I

      Dr. Ken Grauer on Killing Patients Just to Get a Temporary Pulse With Epinephrine – Part II

      There will be more responses to the comments of Dr. Grauer. Also, tomorrow I will post the answer to last Sunday’s question, which is relevant to this continuing problem of a complete lack of evidence of improved survival.

      There is no room for eliteist like you in the profession. So instead of telling us not to kill patients with Epi, how about YOU give YOUR patients a chance with it.

      Why don’t I dance around the patient chanting voodoo spells. It would be less likely to be harmful, but would not be any less beneficial?

      I love being called elitist, but please send me some money, so that I can live in the style of the elite. It makes a poor grunt like me feel important. However, I figure that your imagined insult is just as misinformed as everything else you write.

      We need to stop harming patients with drugs that have no evidence of benefit.

      We need to demand that our standards of care be studied.

      .

      • I want you to show me statistics that show how many of these patients had brain function before Epi was pushed, then show me what the percentage of brain function loss there was. You are so high stron about this, show me. I want to see how you can determine that the brain function loss was do to Epi and not that of downtime/cause of arrest.

        • Anonymous,

          I want you to show me statistics that show how many of these patients had brain function before Epi was pushed, then show me what the percentage of brain function loss there was. You are so high stron about this, show me. I want to see how you can determine that the brain function loss was do to Epi and not that of downtime/cause of arrest.

          I never stated that this is proof of harm.

          I am stating that this is evidence that epinephrine is probably harmful.

          This along with the complete absence of evidence of benefit from epinephrine makes epinephrine the biggest witchcraft of cardiac arrest.

          Nobody needs to prove that any drug is harmful, but somebody must prove that the drug is beneficial.

          There is no evidence of any benefit in survival – epinephrine is just unicorn medicine. We are sprinkling magic fairy dust and pretending that we are doing something good. We are fooling ourselves.

          Until there is evidence of benefit, there is enough evidence of harm to limit epinephrine to randomized controlled trials to learn what the real effects of epinephrine are.

          Since there is no evidence of any improvement in survival, patients will not lose anything.

          .

          • But ROSC is one step closer. It’s better then nothing and gives you something to possibly work with. You say it PROBABLY causes harm, with no evidence your just as bad as te people you are arguing with. And your title for your little story gives the impression that you do in fact think that Epi kills. Which you says yourself has not been proven.

            • Anonymous,

              But ROSC is one step closer.

              No.

              We don’t know if what we do to the patient to get ROSC brings us one step closer to long-term survival.

              We don’t know if what we do to the patient to get ROSC takes us one step farther away from long-term survival.

              We don’t know if what we are doing is bringing us one step closer in some patients, but taking us one step farther away in other patients.

              And things are probably much more complicated that anything that can be explained as just one step in either direction.

              It’s better then nothing and gives you something to possibly work with.

              How do you know that the patient wasn’t more likely to be resuscitated without the epinephrine-induced ROSC?

              Why don’t we give everyone High-Dose Epinephrine, if getting ROSC is what matters?

              High-Dose Epinephrine is better than Standard-Dose Epinephrine at producing ROSC.

              Why use small doses, if small doses do not produce ROSC as often?

              If ROSC gives you something you can work with, High-Dose Epinephrine gives you more ROSC to work with.

              You claim more ROSC is better. Why not High-Dose Epinephrine?

              You say it PROBABLY causes harm, with no evidence your just as bad as te people you are arguing with.

              I included links to some of the evidence in what I already wrote.

              The evidence is not proof, and I never claimed that it is proof, but it certainly is evidence.

              The evidence looks at survival.

              The evidence is consistent with all of the other studies that have looked at the effect of epinephrine on survival

              There is no evidence of epinephrine producing any kind of survival benefit.

              And your title for your little story gives the impression that you do in fact think that Epi kills. Which you says yourself has not been proven.

              Yes, I do think that epinephrine kills.

              No, this has not been proven.

              There is nothing inconsistent about that.

              We have to look at the overall evidence.

              There is no evidence of any quality that epinephrine improves survival.

              There is a lot of evidence of moderate quality that epinephrine kills, especially the brain.

              Probability is strongly against epinephrine being of benefit, when given to all cardiac patients. If there is any benefit, the harm it does in producing ROSC, is greater than the benefit.

              Epinephrine may be of benefit in some specific cases of cardiac arrest, but nobody appears to be trying to find out.

              All of the effort appears to be on discouraging research, so that we cannot come up with clear evidence of just how bad epinephrine is.

              .

  9. With all due respect to you Rogue Medic – I sincerely think your views would be more likely to receive wider acceptance (even if there wasn’t necessarily agreement) – IF you stopped accusing your readers of “Killing Patients Just to Get a Temporary Pulse with Epinephrine”.

    I have revised my synthesis (and my opinion) of the likely impact of papers like the Hagihara publication in this week’s issue of JAMA. The Hagihara publication does NOT in any way “prove” that Epinephrine “causes” neurologic impairment – because ~90% of the patients in his study were found in OHCA with PEA/Asystole as their initial rhythm. These patients therefore almost certainly ALREADY HAD neurologic injury BEFORE the Epi was given. Epi merely increased the chance of getting back a pulse in these patients. Deciding to use Epi on such pts was the mistake – but not because Epi “caused” neurologic injury.

    My revised post on the Use of Epi in Cardiac Arrest can be found at: https://www.kg-ekgpress.com/acls_comments-_issue_10/

    My BOTTOM LINE is the following:
    – There is no evidence to date establishing a cause-and-effect relationship between Epi use for cardiac arrest and impaired neurologic outcome.
    – Observational data is not proof; it merely suggests hypotheses and a need for additional study.
    – In the meantime (awaiting such studies) — Clinicians remain with the dilemma of simply not having any therapeutic drugs proved to improve survival from cardiac arrest, even though they do have an agent that does increase the chance of ROSC. Debate will continue on whether that agent (Epinephrine) should still be used.

    MY OPINION: Until such time that we have proof of harm from use of Epi in patients with cardiac arrest — I think:

    1) Epinephrine should continue to be used as it has up until now for IN-hospital cardiac arrest. (Bigger issues regarding in-hospital decision-making relate to determination of which patients should or should not be resuscitated — but once that decision has been made, we are committed to doing all we can to increase likelihood of ROSC).

    2) Epinephrine should continue to be used as it has up until now for OUT-of-hospital cardiac arrest when the initial mechanism of arrest is Pulseless VT or VFib.

    3) It is reasonable not to use Epi for OUT-of-hospital cardiac arrest when the initial mechanism of arrest is PEA/Asystole — especially if information about the onset of arrest is lacking and no bystander CPR has been done. Realistic chances of resuscitating such patients with restoration of intact neurologic function are almost negligible for such patients. Epi increases the chance of restoring a pulse — which could lead to a state even less desirable than death.

    4) My reason for 3) is not because Epi “causes” neurologic injury (since there to date is no evidence proving this) — but rather because the finding of PEA/Asystole in OHCA almost certainly portends irreversible insultregardless of whatever interventions are attempted.

    ACKNOWLEDGEMENT: Others may have different opinions …

  10. I think I’ve decided that when Rogue Medic talks, it’s in Sheldon Cooper’s voice.

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