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

- Rogue Medic

How Effective Is Epinephrine for Improving Survival Among Patients in Cardiac Arrest?

Sun, 30 Jun 2019 22:20:08 -0400 by
   

There have been two studies comparing epinephrine with placebo to treat out of hospital cardiac arrest. The Jacobs study was stopped early, because of interference by those who do not want to know if their medicine actually works.[1] The purpose of research is to determine, as objectively as possible, if a treatment is better than placebo nothing.  

Click on the image to make it larger.  

Even the small sample size shows a impressive p values of <0.001 for both ROSC (Return Of Spontaneous Circulation) and being admitted to the hospital. Unfortunately, that does not lead to outcomes that are better than placebo.

The Perkins study (PARAMEDIC2) did not find a significant difference between adrenaline (epinephrine in non-Commonwealth countries) and placebo.[2] The Jacobs study also did not find a difference, but the numbers were small, due to the interference by the less than knowledgeable. Following the Jacobs study, some intervention proponents have suggested that the problem is not a lack of evidence of benefit, but need to look at the evidence from the right perspective. The inadequate evidence is not “inadequate”, but really just misunderstood. All we need to do is use a method of analysis that compensates for the tiny sample size. A Bayesian approach will produce the positive outcome that is not justified by so few patients.[3]

What happens when the numbers are combined, so that the sample size is large enough to eliminate the need for statistical chicanery to come up with something positive?

The outcomes do not improve.  

Neither standard dose adrenaline, high-dose adrenaline,vasopressin nor a combination of adrenaline and vasopressin improved survival with a favourable neurological outcome.[4]
 

If the Bayesian approach were appropriate, then the much larger sample size would have provided more than enough patients to confirm the optimism of the epinephrine advocates. The result is still not statistically significant. Maybe a much, much larger study will show a statistically significant, but tiny, improvement in outcomes with epinephrine, but don’t hold your breath for that. It took half a century to produce the first study, then seven more years for the second. With the cost of research and the problems coordinating such a large study, it is more likely that the guidelines will continue to recommend spending a lot of time and money giving a drug that diverts attention from the interventions that do improve outcomes.

There is still no evidence that adrenaline provides better outcomes than placebo in human cardiac arrest patients.

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Footnotes:

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[1] Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial Jacobs IG, Finn JC, Jelinek GA, Oxer HF, Thompson PL. Resuscitation. 2011 Sep;82(9):1138-43. doi: 10.1016/j.resuscitation.2011.06.029. Epub 2011 Jul 2. PMID: 21745533

Free Full Text PDF Download from semanticscholar.org  

This study was designed as a multicentre trial involving five ambulance services in Australia and New Zealand and was accordingly powered to detect clinically important treatment effects. Despite having obtained approvals for the study from Institutional Ethics Committees, Crown Law and Guardianship Boards, the concerns of being involved in a trial in which the unproven “standard of care” was being withheld prevented four of the five ambulance services from participating.

In addition adverse press reports questioning the ethics of conducting this trial, which subsequently led to the involvement of politicians, further heightened these concerns. Despite the clearly demonstrated existence of clinical equipoise for adrenaline in cardiac arrest it remained impossible to change the decision not to participate.

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[2] A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. Perkins GD, Ji C, Deakin CD, Quinn T, Nolan JP, Scomparin C, Regan S, Long J, Slowther A, Pocock H, Black JJM, Moore F, Fothergill RT, Rees N, O’Shea L, Docherty M, Gunson I, Han K, Charlton K, Finn J, Petrou S, Stallard N, Gates S, Lall R; PARAMEDIC2 Collaborators. N Engl J Med. 2018 Aug 23;379(8):711-721. doi: 10.1056/NEJMoa1806842. Epub 2018 Jul 18. PMID: 30021076

Free Full Text from N Engl J Med.

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[3] Regarding “Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial”. Youngquist ST, Niemann JT. Resuscitation. 2012 Apr;83(4):e105; author reply e107. doi: 10.1016/j.resuscitation.2011.09.035. Epub 2012 Jan 18. No abstract available. PMID: 22266068

Free Full Text from Resuscitation.

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[4] Adrenaline and vasopressin for cardiac arrest. Finn J, Jacobs I, Williams TA, Gates S, Perkins GD. Cochrane Database Syst Rev. 2019 Jan 17;1:CD003179. doi: 10.1002/14651858.CD003179.pub2. PMID: 30653257    

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Filed Under: ACLS, ALS, Anti-Science, Cardiac Arrest, CPR, Critical Judgment, EBM, Epinephrine, Ethics, Evidence, Pharmacology, Research, Risk Management

Closed chest compressions reduce survival in an animal model of haemorrhage-induced traumatic cardiac arrest

Fri, 31 May 2019 19:00:44 -0400 by
   

This is an animal study, rather than a human study, but it has fewer disadvantages than the usual animal studies of medical cardiac arrest. Animals do not develop the comorbidities that humans do, but have artificially created heart attacks, rather than by the development of actual heart disease. In studying trauma, this is less of a problem, since trauma is artificially created. This study is much more representative of penetrating injuries with a low velocity objects, than blunt force trauma, or penetrating injury with a high velocity object.

Are we really killing trauma patients with our chest compressions?

Maybe. This is one small study (39 pigs), but it does raise questions about the ways we can minimize the harm we cause.

 

 
CCC were associated with increased mortality and compromised haemodynamics compared to intravenous fluid resuscitation. Whole blood resuscitation was better than saline.[1]

 
A soft tissue injury was created, with 3 shots to the right thigh using a captive bolt (Cash Special, Accles and Shelvoke, Sutton Coldfield, UK). Two minutes later animals underwent a controlled haemorrhage (30% blood volume) at an exponentially reducing rate as previously described12 until the mean arterial blood pressure (MAP) was 45 mmHg. Blood was collected into CPD (citrate phosphate dextrose) and stored at room temperature until required for later transfusion.[1]
 

Image source

 

This study, conducted in an animal model of haemorrhage-induced traumatic cardiac arrest, has demonstrated that chest compressions confer no benefit over fluid resuscitation alone, and blood should be the fluid therapy of choice.[1]

  That seems to be concluding too much, since this is just one study, but it does reinforce the results of other, similar studies. We should study the outcomes in humans, since there does appear to be equipoise. There never was a physiological justification for chest compressions in traumatic cardiac arrest which appears to be due to hemorrhage. Now there is more evidence that chest compressions produce more harm than benefit in traumatic cardiac arrest which appears to be due to hemorrhage.

 
One study using a baboon traumatic cardiac arrest model found that the improvements in haemodynamics seen with chest compressions for normovolaemic cardiac arrest were not reproduced in hypovolaemic arrest.14 The authors suggested that CCC should not delay correction of the underlying deficit causing TCA, but the study was undertaken in only three animals, perhaps limiting its clinical relevance. A more recent study using a canine model of pulseless electrical activity in TCA found no benefit of chest compressions over fluid therapy alone or fluid combined with chest compressions; in fact the chest compression only group had worse survival, base deficit and ejection fraction.15 The authors concluded that further research was required to determine whether CPR has a role for the patient in haemorrhagic shock.[1]

  Most important is that the outcome is ROSC (Return Of Spontaneous Circulation), not return to normal neurological function. Since these are pigs, even the appearance of normal neurological function may not mean anything in humans. Still, the treatment is not evidence-based, so there does not appear to be a good reason to prefer to continue using compressions for traumatic cardiac arrest which appears to be due to hemorrhage.

Here in America, we are unlikely to do the research, because we are more concerned with appearances than with improving outcomes for patients. Maybe somebody in Britain or Australia will have to demonstrate some responsibility, so we can stop using chest compressions to kill trauma patients.

  Footnotes:

  [1] Closed chest compressions reduce survival in an animal model of haemorrhage-induced traumatic cardiac arrest. Watts S, Smith JE, Gwyther R, Kirkman E. Resuscitation. 2019 May 9;140:37-42. doi: 10.1016/j.resuscitation.2019.04.048. [Epub ahead of print]

PMID: 31077754

Free Full Text from Resuscitation

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Filed Under: ACLS, CPR, Heresy, Potentially Reversible Causes, Research, Trauma

ILCOR wants the appearance of public comments with less than half the substance

Mon, 01 Apr 2019 14:45:53 -0400 by
 

The International Liaison Committee on Resuscitation (ILCOR) shows its priorities in the way it handles its problem with public comments.
 

Last week ILCOR posted the two new draft CoSTRs listed below for public comment. It became apparent that the commenting link was broken and those who visited the site could not comment. We apologize for the inconvenience. The commenting link is now fixed and we invite you to comment at ilcor.org/costr.

  • Advanced Airway Management During Adult Cardiac Arrest
  • Vasopressors in Adult Cardiac Arrest

    • As a reminder, the public comment period will close on 4 April 2019.[1]

     

    ILCOR made a mistake that prevented public comments from being submitted for most of the public comment period.

    ILCOR is so interested in your public comments that they have decided to send out an email to let people know that they have the same drop dead date for the comments as before, but this time they might actually be able to get the comments to work. Maybe.

    The lack of evidence of benefit of epinephrine (adrenaline in Commonwealth countries) has lasted over half a century, so what is the rush to get these new guidelines out?

    There is only one outcome that matters – survival without severe brain damage.
     


     

    ILCOR evaluates 23 outcomes.

    ILCOR considers 15 of these outcomes critical, but they are really just 5 outcomes, with some of them repeated over different rhythms. These are (in increasing order of importance to the only one that matters):

    1. For the critical outcome of survival to hospital discharge, 2. For the critical outcome of survival at 3 months, 3. For the critical outcome of favorable neurologic outcome at hospital discharge, 4. For the critical outcome of survival with unfavorable neurologic outcome at 3 months, 5. For the critical outcome of favorable neurologic outcome at 3 months,

    Many of them are repeated for each cardiac arrest rhythm or for each vasopressor, or vasopressor cocktail:

    1. Epinephrine plus vasopressin compared to epinephrine only – Any rhythm 2. Initial vasopressin compared to initial epinephrine – Any rhythm 3. Epinephrine compared to placebo – Non-shockable rhythms 4. Epinephrine compared to placebo – Shockable rhythms 5. Epinephrine compared to placebo – Any initial rhythm

    There is only one outcome that matters – survival without severe brain damage.

    There is only one study that was large enough to answer this:
     

    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.[2]

     

    If the people at ILCOR really think that epinephrine is beneficial in cardiac arrest, they should encourage a much larger study.

    There were 4,000 patients in each group – 4,000 placebo and 4,000 epinephrine.

    Maybe with 8,000 patients in each group, the ever decreasing “trend toward better outcome” will reach significance. Maybe it will be shown to be just another insignificant appearance of a “trend” that is the result of having so few survivors to compare.

    There were only 161 survivors without severe brain damage out of 8,000 cardiac arrest patients – 74 placebo and 87 epinephrine.

    Those resuscitated before receiving epinephrine/placebo were excluded from the study, so this is not a case of EMS that only has a 2% resuscitation rate. The focus on epinephrine is a focus on the patients least likely to be resuscitated and a focus on counterproductive outcomes.

    Almost all of our good outcomes (without severe brain damage) will be without epinephrine, because these resuscitations happen before epinephrine can be give by even the most aggressive epi enthusiast.

    What we are doing is making excuses for memorizing ineffective interventions and requiring their application is a specific way, in order to determine the quality of care. We are promoting fantasy.

    We learned that distracting from the quality of chest compressions is the most deadly thing we can do in resuscitation.

    CPR = only chest compressions – the exception is when the arrest is believed to be due to a respiratory event, such as when the Smurf sign or a respiratory/choking history is present. Chest compressions provide all of the pulmonary resuscitation that a human needs for a non-respiratory event and the respiratory events are not easily missed.

    Why require a whole bunch of skills be applied for such a tiny portion of good outcomes among cardiac arrest patients?

    Why not give up on requiring these skills when the evidence makes it clear that there is no benefit?

    All we are doing is adding cognitive load to make us feel like we are doing something special.

    We could learn something that actually benefits patients, such as how to assess patients when giving high-dose NTG (NiTroGlycerin or GTN GlycerylTriNitrate in Commonwealth countries) for even hypotensive CHF/ADHF (Congestive Heart Failure/Acute Decompensated Heart Failure), where we can make much more of a difference and prevent cardiac arrest, but we don’t.[3],[4],[5]
     


     

    Cognitive load is not just a problem for paramedics and nurses, or med/surg doctors, but also for emergency physicians:

    Cognitive Load and the Emergency Physician
    April 12, 2016
    James O’Shea
    emDocs
    Article

    Why are we distracting everyone from things that do improve the only outcome that matters, in order to promote things that do not improve any outcome that matters?

    Here is what I wrote –
     

    The primary source for the recommendation to keep things the same is a brand new study – PARAMEDIC2.

    This showed no statistically significant improvement in the only outcome that matter – survival without severe brain damage.

    A larger study might show that there is a real improvement – or it may put the epi hypothesis out of its misery.

    I will eventually have a cardiac arrest. If I am resuscitated, whom will ILCOR send to change my diaper, and attend to the other things I can no longer attend to?

    We need evidence of a significant benefit in order to justify distracting everyone from interventions that actually do improve survival without severe brain damage.

    .

     

    The commenting link is now fixed and we invite you to comment at ilcor.org/costr

    Maybe they will pay attention. Dr. Rory Spiegel of EM Nerd has a detailed comment that is also critical of ILCOR’s proposed “strong recommendation” of epinephrine.

    –

    Footnotes:

    –

    [1] Vasopressors in Adult Cardiac Arrest
    Time left for commenting: 11 days 15:49:49
    ILCOR staff
    Created: March 21, 2019 · Updated: March 21, 2019
    Draft for public comment
    Consensus on Science with Treatment Recommendations (CoSTR)
    Vasopressors in Adult Cardiac Arrest page for comments until April 04, 2019 at 06:00 Eastern Time

    –

    [2] A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest.
    Perkins GD, Ji C, Deakin CD, Quinn T, Nolan JP, Scomparin C, Regan S, Long J, Slowther A, Pocock H, Black JJM, Moore F, Fothergill RT, Rees N, O’Shea L, Docherty M, Gunson I, Han K, Charlton K, Finn J, Petrou S, Stallard N, Gates S, Lall R; PARAMEDIC2 Collaborators.
    N Engl J Med. 2018 Aug 23;379(8):711-721. doi: 10.1056/NEJMoa1806842. Epub 2018 Jul 18.
    PMID: 30021076

    Free Full Text from N Engl J Med.
     

    In a Bayesian analysis that used an assumption of no benefit from adrenaline, the posterior probability that the absolute rate of survival was at least 1 percentage point higher in the epinephrine group than in the placebo group was 37% (Fig. S3 in the Supplementary Appendix). The probability that the absolute survival rate was at least 2 percentage points higher was 0.2%. With respect to the rate of survival with a favorable neurologic outcome at hospital discharge, the probabilities that the rate was at least 1 or 2 percentage points higher with epinephrine were 1.9% and 0%, respectively (Fig. S4 in the Supplementary Appendix).

     

    The probability of a good outcome (no severe brain damage) is not improved with epinephrine.

    If we want to improve outcomes, we need to look elsewhere, because there is nothing to be gained with epi.

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    [3] Intravenous nitrates in the prehospital management of acute pulmonary edema.
    Bertini G, Giglioli C, Biggeri A, Margheri M, Simonetti I, Sica ML, Russo L, Gensini G.
    Ann Emerg Med. 1997 Oct;30(4):493-9.
    PMID: 9326864 [PubMed – indexed for MEDLINE]

    –

    [4] Unreasonable Fear of Hypotension and High-Dose NTG – Part I
    Thu, 29 Aug 2013
    Rogue Medic
    Article

    –

    [5] Unreasonable Fear of Hypotension and High-Dose NTG – Part II
    Wed, 04 Sep 2013
    Rogue Medic
    Article

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    Filed Under: ACLS, Airway Management, Cardiac Arrest, Cardiology, CPR, Critical Judgment, Epinephrine, Heresy, NTG, Pharmacology, Research

    What Treatments May Be De-Emphasized by EM/EMS in 2019? Part II

    Wed, 09 Jan 2019 15:00:19 -0500 by
     

    I showed the problems with amiodarone for both live patients and dead patients in Part I. The higher the quality of the evidence, the less the evidence supports the use of amiodarone on humans.

    Amiodarone is all sales pitch and no medical benefit, but Dr. Kudenchuk keeps trying to spin the results like an acupuncturist, when the evidence clearly does not support Dr. Kudenchuk’s claims.[1]
     

    What else should be de-emphasized?

    Obviously, adrenaline (epinephrine in non-Commonwealth countries) for cardiac arrest. As the quality of the epinephrine research has improved, the claims of supposed benefits have disappeared.[2], [3]

    Now, the goalposts have shifted, again, and the claims are that some other dosing is safe and effective, even though the evidence to support these claims does not exist. This is alternative medicine. This is dishonest. This is experimenting on patients without any kind of ethical approval, or collection of data, or anything else that would accompany a true experiment. We are learning that we are very good at lying to ourselves, but we knew that.

    Eventually, we may be claiming that we have not studied what happens when we stand on one leg while giving epinephrine.

    How can we possibly stop using adrenaline if we have not proven that it doesn’t work when standing on one leg? How can we refuse to provide this one legged hope to patients?

    We are sorry for what we did to your _______, but we consider justifying doing something harmful, based on low quality evidence and even lower quality excuses, to be more important than the outcomes of our patients. If we don’t throw in the kitchen sink, how can we claim that we did everything we could for to your _______?
     


    Click on the image to make it larger.
    I modified the original to add the outcomes reported by PARAMEDIC2. Severe neurological impairment is the wording from the conclusion, but that would not fit. If you think that harm is not an accurate synonym for impairment, you may be dangerous to patients.
    Source of original – R.E.B.E.L. EM – Beyond ACLS: Cognitively Offloading During a Cardiac Arrest
     

    If the next revision of ACLS/ILCOR (Advanced Cardiac Life Support/International Liaison Committee on Resuscitation) does not state that epinephrine/adrenaline should be limited to use in high quality research, it will be encouraging abuse of patients.

    This is alternative medicine. This is not medicine.

    The difference is that real medicine relies on valid evidence that it works, while alternative medicine relies on marketing strategies and misinformation.

    Do you want to be treated by someone who can tell the difference between these approaches?

    Medicine requires doing what is best for the patient.

    Alternative medicine requires doing what makes the guru look best, so that the guru can keep making sales.

    The doctors promoting this unethical approach do not appear to be ashamed of what they are doing, but they keep making excuses. We need to make it clear that their excuses are not ethical.

    To all of the doctors claiming that a drip works. Demonstrate that you are ethical and competent. Show that what you are doing improves outcomes that matter to patients, in a high quality study, or stop.

    If doctors won’t do that, maybe we should add DNA (Do Not Amio) and DNE (Do Not Epi) to our list of advance directives, for those who do not think that resuscitation to a come, where sepsis and aspiration pneumonia are what we aspire to.

    –

    Footnotes:

    –

    [1] Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest.
    Kudenchuk PJ, Brown SP, Daya M, Rea T, Nichol G, Morrison LJ, Leroux B, Vaillancourt C, Wittwer L, Callaway CW, Christenson J, Egan D, Ornato JP, Weisfeldt ML, Stiell IG, Idris AH, Aufderheide TP, Dunford JV, Colella MR, Vilke GM, Brienza AM, Desvigne-Nickens P, Gray PC, Gray R, Seals N, Straight R, Dorian P; Resuscitation Outcomes Consortium Investigators.
    N Engl J Med. 2016 May 5;374(18):1711-22. doi: 10.1056/NEJMoa1514204. Epub 2016 Apr 4.
    PMID: 27043165

    Free Full Text from NEJM.

    CONCLUSIONS Overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival or favorable neurologic outcome than the rate with placebo among patients with out-of-hospital cardiac arrest due to initial shock-refractory ventricular fibrillation or pulseless ventricular tachycardia.

     

    Here are some comments from Dr. Kudenchuk, which contradict the conclusion of Dr. Kudenchuk’s study:
     

    This trial shows that amiodarone and lidocaine offer hope for bringing patients back to life and into the hospital after cardiac arrest,” said principal study author Peter Kudenchuk, M.D.

     

    This trial shows that amiodarone and lidocaine offer no hope for outcomes that matter to patients.
     

    Importantly, there was a significant improvement in survival to hospital discharge with either drug when the cardiac arrest was bystander-witnessed.”

     

    There is no truth to Dr. Kudenchuk’s claim. This is what the authors of the study actually wrote:
     

    We observed an interaction of treatment with the witnessed status of out-of-hospital cardiac arrest, which is often taken as a surrogate for early recognition of cardiac arrest, a short interval between the patient’s collapse from cardiac arrest and the initiation of treatment, and a greater likelihood of therapeutic responsiveness. Though prespecified, this subgroup analysis was performed in the context of an insignificant difference for the overall analysis, and the P value for heterogeneity in this subgroup analysis was not adjusted for the number of subgroup comparisons. Nonetheless, the suggestion that survival was improved by drug treatment in patients with witnessed out-of-hospital cardiac arrest, without evidence of harm in those with unwitnessed arrest, merits thoughtful consideration.

     

    The best that can be stated about these drugs is that if the researchers used a large enough study, they might be able to find a statistically significant result – or the researchers may demonstrate that this was just another example of a statistically insignificant run of luck, which means nothing and is just as likely to have gone the other way.

    A run of heads in a row, while flipping a coin is a reason to examine the coin for bias, but if no bias is found, it is expected to be just what is expected to happen in a large number of coin flips. A lack of understanding of coincidence leads to faulty conclusions.

    The difference in outcomes, that Dr. Kudenchuk claims is significant, not statistically significant.

    Does Dr. Kudenchuk not understand the way research works or does Dr. Kudenchuk have some unstated motive for distorting the results? It appears that the New England Journal of Medicine refused to publish the conclusion that Dr. Kudenchuk wanted, so Dr. Kudenchuk is using more gullible people to spread his misinformation.

    Go ahead and read the full paper, which is available from NEJM here.

    Also read Dr. Kudenchuk’s press release, which misrepresents the results of Dr. Kudenchuk’s study. You would think that Dr. Kudenchuk would know better.
     

    Antiarrhythmic drugs found beneficial when used by EMS treating cardiac arrest
    NHLBI NEWS|News Release
    April 4, 2016, 9:00 AM EDT
    Press Release
     

    I have nothing to hide. I want you to look all of the evidence.
     

    Dr. Kudenchuk is Misrepresenting ALPS as ‘Significant’
    Tue, 12 Apr 2016
    Rogue Medic
    Article
     

    Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest
    Mon, 04 Apr 2016
    Rogue Medic
    Article

    –

    [2] Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial
    Jacobs IG, Finn JC, Jelinek GA, Oxer HF, Thompson PL.
    Resuscitation. 2011 Sep;82(9):1138-43. Epub 2011 Jul 2.
    PMID: 21745533 [PubMed – in process]

    Free Full Text PDF Download from semanticscholar.org
     

    This study was designed as a multicentre trial involving five ambulance services in Australia and New Zealand and was accordingly powered to detect clinically important treatment effects. Despite having obtained approvals for the study from Institutional Ethics Committees, Crown Law and Guardianship Boards, the concerns of being involved in a trial in which the unproven “standard of care” was being withheld prevented four of the five ambulance services from participating.

     

    In addition adverse press reports questioning the ethics of conducting this trial, which subsequently led to the involvement of politicians, further heightened these concerns. Despite the clearly demonstrated existence of clinical equipoise for adrenaline in cardiac arrest it remained impossible to change the decision not to participate.

     

    The results do not show an improvement in the any outcome that matters to patients.
     

    CONCLUSION: Patients receiving adrenaline during cardiac arrest had no statistically significant improvement in the primary outcome of survival to hospital discharge although there was a significantly improved likelihood of achieving ROSC.

     

    –

    [3] A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest.
    Perkins GD, Ji C, Deakin CD, Quinn T, Nolan JP, Scomparin C, Regan S, Long J, Slowther A, Pocock H, Black JJM, Moore F, Fothergill RT, Rees N, O’Shea L, Docherty M, Gunson I, Han K, Charlton K, Finn J, Petrou S, Stallard N, Gates S, Lall R; PARAMEDIC2 Collaborators.
    N Engl J Med. 2018 Jul 18. doi: 10.1056/NEJMoa1806842. [Epub ahead of print]
    PMID: 30021076

    Free Full Text from NEJM

    It appears that the full text of PARAMEDIC2 is no longer available for free from NEJM, but there is the option of registering for 3 free papers a month (Register for 3 FREE subscriber-only articles each month.) in a red pop-up banner at the bottom of the page.

    Once again, the results do not show an improvement in the any outcome that matters to patients.
     

    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.

     

    .

    Filed Under: ACLS, Cardiac Arrest, Critical Judgment, Ethics, Evidence, Heresy, Research

    What Treatments May Be De-Emphasized by EM/EMS in 2019? Part I

    Tue, 01 Jan 2019 22:56:04 -0500 by
     

    EM (Emergency Medicine) and EMS (Emergency Medical Services) have already started to eliminate/decrease use of a lot of our failed treatments, because people started to see through our excuses. Atropine for asystole stuck around for a long time, then just vanished.[1]. Calcium for cardiac arrest is also something that used to be standard of care, then we raised our standards.

    We need to keep raising our standards, because our patients’ outcomes – their lives, their brains, their everything – depend on raising our standards.

    We used to give antiarrhythmics to almost anyone with a cardiac complaint. Then there was CAST (The Cardiac Arrhythmia Suppression Trial[2]). While CAST did not study lidocaine, it did study longer term use of antiarrhythmics. Lidocaine is too dangerous for long term use, so the results of CAST may be much worse for lidocaine. We thought that the increased deaths among patients with frequent PVCs (Premature Ventricular Contractions) after having a heart attack was due to a problem with the conduction system. PVCs indicate a problem with conduction and antiarrhythmics cause the PVCs to go away.
     

    Before receiving the antiarrhythmic (PVCs are circled in red).


     

    After receiving the antiarrhythmic.


     

    Problem solved.

    Now the problem is, How do we get paid more? These drugs were the biggest selling drugs at the time. They making the drug companies a fortune. Whichever company made the drug that saved the most lives would make a lot more money then the others. Provide evidence that ______ saves more lives than all of the others.

    The problem of the PVCs was solved, but the solution was killing many more patients than not giving drugs.

    The result was not celebrated by the drug companies. The patients taking antiarrhythmics were dying at three times the rate of the patients taking placebos. A plausible physiological mechanism suggested the drugs would save lives, but that was based on an assumption that was not justified. This is the kind of reasoning that appeals to those who reject EBM (Evidence-Based Medicine). The evidence should convince these EBM opponents of the folly of relying on physiology and on a plausible explanation to justify not looking for the evidence that might expose their unreasonable assumptions. These otherwise reasonable people start making excuses for unreasonable assumptions, because they believe. They seem to need to convince others to join in and multiply their mistakes.[3]

    The PVCs appear to have been just an indicator of an unhealthy heart.

    Getting rid of the PVCs may have made the conduction in the heart less healthy.

    Giving the drugs may have killed tens of thousands of patients.

    Antiarrhythmic use decreased dramatically after the harm demonstrated in CAST, but some drug pushers are trying to get one of the worst antiarrhythmics (amiodarone, now in a new formula) to make a comeback, by creatively spinning research to claim results the research was never designed to evaluate.

    Not having learned from the evidence, even though he has been the lead author on some of it, Dr. Peter Kudenchuk has been claiming that in EMS witnessed arrests, there was a significant improvement, even though his own published results contradict this claim. Here is what the results actually state:
     

    Though prespecified, this subgroup analysis was performed in the context of an insignificant difference for the overall analysis, and the P value for heterogeneity in this subgroup analysis was not adjusted for the number of subgroup comparisons. Nonetheless, the suggestion that survival was improved by drug treatment in patients with witnessed out-of-hospital cardiac arrest, without evidence of harm in those with unwitnessed arrest, merits thoughtful consideration.[4]

     

    Amiodarone has also been shown to be horrible for patients with ventricular tachycardia with a pulse. Amiodarone is so ineffective, that the rate of severe side effects is greater than the rate of improved outcomes. Amiodarone is more likely to make your patient’s medical condition much worse, but it is still considered to be the standard of care and amiodarone is still in EMS protocols.[5]

    Maybe amiodarone can produce better results if it is used for execution by lethal injection.

    I am expecting that there will be more failed treatments removed from our standards of care.

    We need to raise our standards to improve outcomes, not lower our standards to make us look better than we are.

    Continued in Part II. I will add Part III and others at some point and provide the links here.

    –

    Footnotes:

    –

    [1] Why Did We Remove Atropine From ACLS?
    Rogue Medic

    Part I
    Sun, 13 Oct 2013

    Part II
    Wed, 16 Oct 2013

    –

    [2] Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial.
    Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL, et al.
    N Engl J Med. 1991 Mar 21;324(12):781-8.
    PMID: 1900101 [PubMed – indexed for MEDLINE]

    Free Full Text from NEJM.
     

    CONCLUSIONS. There was an excess of deaths due to arrhythmia and deaths due to shock after acute recurrent myocardial infarction in patients treated with encainide or flecainide. Nonlethal events, however, were equally distributed between the active-drug and placebo groups. The mechanisms underlying the excess mortality during treatment with encainide or flecainide remain unknown.

    –

    [3] Why US EMS will never get to sit at the adult table – The Appeal to Authority
    Sun, 04 May 2014
    Rogue Medic
    Article

    Since Mike cites the original parachute study, as if it is not satire, it is amusing to point out that there is a new Parachute Study! Read Dr. Radecki’s description of this satirical poke at those who do not understand research in the satire issue of the BMJ, which they put out every Christmas as sort of a British IgNobel.

    Don’t Bother With the Parachute!
    Emergency Medicine Literature of Note
    Dr. Ryan Radecki
    December 21, 2018
    Article
     

    Parachute use to prevent death and major trauma when jumping from aircraft: randomized controlled trial.
    Yeh RW, Valsdottir LR, Yeh MW, Shen C, Kramer DB, Strom JB, Secemsky EA, Healy JL, Domeier RM, Kazi DS, Nallamothu BK; PARACHUTE Investigators.
    BMJ. 2018 Dec 13;363:k5094. doi: 10.1136/bmj.k5094. Erratum in: BMJ. 2018 Dec 18;363:k5343.
    PMID: 30545967

    Free Full Text from BMJ.

    –

    [4] Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest.
    Kudenchuk PJ, Brown SP, Daya M, Rea T, Nichol G, Morrison LJ, Leroux B, Vaillancourt C, Wittwer L, Callaway CW, Christenson J, Egan D, Ornato JP, Weisfeldt ML, Stiell IG, Idris AH, Aufderheide TP, Dunford JV, Colella MR, Vilke GM, Brienza AM, Desvigne-Nickens P, Gray PC, Gray R, Seals N, Straight R, Dorian P; Resuscitation Outcomes Consortium Investigators.
    N Engl J Med. 2016 May 5;374(18):1711-22. doi: 10.1056/NEJMoa1514204. Epub 2016 Apr 4.
    PMID: 27043165

    Free Full Text from NEJM.

    CONCLUSIONS Overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival or favorable neurologic outcome than the rate with placebo among patients with out-of-hospital cardiac arrest due to initial shock-refractory ventricular fibrillation or pulseless ventricular tachycardia.

     

    Dr. Kudenchuk is Misrepresenting ALPS as ‘Significant’
    Tue, 12 Apr 2016
    Rogue Medic
    Article
     

    Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest
    Mon, 04 Apr 2016
    Rogue Medic
    Article

    –

    [5] The PROCAMIO Trial – IV Procainamide vs IV Amiodarone for the Acute Treatment of Stable Wide Complex Tachycardia
    Rogue Medic
    Wed, 17 Aug 2016
    Article
     

    Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study.
    Ortiz M, Martín A, Arribas F, Coll-Vinent B, Del Arco C, Peinado R, Almendral J; PROCAMIO Study Investigators.
    Eur Heart J. 2016 Jun 28. pii: ehw230. [Epub ahead of print]
    PMID: 27354046

    Free Full Text from European Heart Journal.
     

    Amiodarone or procainamide for the termination of sustained stable ventricular tachycardia: an historical multicenter comparison.
    Marill KA, deSouza IS, Nishijima DK, Senecal EL, Setnik GS, Stair TO, Ruskin JN, Ellinor PT.
    Acad Emerg Med. 2010 Mar;17(3):297-306.
    PMID: 20370763 [PubMed – indexed for MEDLINE]

    Free Full Text from Academic Emergency Medicine.
     

    Amiodarone is poorly effective for the acute termination of ventricular tachycardia.
    Marill KA, deSouza IS, Nishijima DK, Stair TO, Setnik GS, Ruskin JN.
    Ann Emerg Med. 2006 Mar;47(3):217-24. Epub 2005 Nov 21.
    PMID: 16492484 [PubMed – indexed for MEDLINE]
     

    Intravenous amiodarone for the pharmacological termination of haemodynamically-tolerated sustained ventricular tachycardia: is bolus dose amiodarone an appropriate first-line treatment?
    Tomlinson DR, Cherian P, Betts TR, Bashir Y.
    Emerg Med J. 2008 Jan;25(1):15-8.
    PMID: 18156531 [PubMed – indexed for MEDLINE]
     

    Effects of intravenous amiodarone on ventricular refractoriness, intraventricular conduction, and ventricular tachycardia induction.
    Kułakowski P, Karczmarewicz S, Karpiński G, Soszyńska M, Ceremuzyński L.
    Europace. 2000 Jul;2(3):207-15.
    PMID: 11227590 [PubMed – indexed for MEDLINE]

    Free Full Text PDF + HTML from Europace
     

    Adenosine for wide-complex tachycardia – diagnostic?
    Thu, 23 Aug 2012
    Rogue Medic
    Article
     

    Low doses of intravenous epinephrine for refractory sustained monomorphic ventricular tachycardia.
    Bonny A, De Sisti A, Márquez MF, Megbemado R, Hidden-Lucet F, Fontaine G.
    World J Cardiol. 2012 Oct 26;4(10):296-301. doi: 10.4330/wjc.v4.i10.296.
    PMID: 23110246 [PubMed]

    Free Full Text from PubMed Central.

    .

    Filed Under: ACLS, Cardiac Arrest, Critical Judgment, EBM, Ethics, Evidence, Heresy, Research

    The Grinch Who Stole Reality

    Fri, 28 Dec 2018 13:00:46 -0500 by
     

    And the Grinch, with his Grinch-feet ice cold in the snow, stood puzzling and puzzling, how could it be so?

    It came without ribbons epi.

    It came without tags amio.

    It came without packages oxygen, boxes tubes or bags.

    And he puzzled and puzzled ’till his puzzler was sore. Then the Grinch thought of something he hadn’t before.

    Maybe Christmas living, he thought…doesn’t come from a store drug.

    Maybe Christmas living, perhaps…means a little bit more!

     

    With apologies to Dr. Seuss (Theodore Geisel) for the modification of his parable.

    There are important differences between the minimal criteria for life and the criteria for a meaningful life. Many of us don’t like to think about that, because many of us don’t like thinking. Thinking can be hard. Making excuses for not thinking – priceless (at least, as long as you don’t think about it).

    We have been focusing on the least honest way of reporting outcomes – a pulse – Oooh!, or maybe even 30 days of a pulse – Oood-Ahhh! After all, reality does not support continuing to do what we have been doing. If we admit that we have been causing harm, then we may have to take responsibility for our actions.

    We do not want to take responsibility for our actions. We were only following orders.

    Doctors, PAs (Physician Assistants), NPs (Nurse Practitioners), nurses, paramedics, EMTs, techs, . . . do not want to take responsibility for what we get paid for. Accountability is for people who think – not for us.

    We have blamed science/evidence for requiring that we confront reality. As explained by Dr. Seuss, we want simple answers that do not require understanding. Give us algorithms to mindlessly follow. Give us mnemonics.

    We have been giving epinephrine (adrenaline in Commonwealth countries) for over half a century with no evidence of safety or improvement in the outcome that matters most.

    Why?

    We haven’t wanted to know.

    The first study to look at the effect of placebo vs. epinephrine on neurological survival was cut short – with only a tiny fraction of what would be needed to produce any kind of statistically useful information, except for some of the true believers, who made the same kinds of mistakes that have been made for other discarded treatments – treatments discarded due to failure to work, discarded due to harm, or discarded due to both.

    Don’t study this. Just believe. Belief makes us feel good. Attack science for encouraging understanding.
     

    This study was designed as a multicentre trial involving five ambulance services in Australia and New Zealand and was accordingly powered to detect clinically important treatment effects. Despite having obtained approvals for the study from Institutional Ethics Committees, Crown Law and Guardianship Boards, the concerns of being involved in a trial in which the unproven “standard of care” was being withheld prevented four of the five ambulance services from participating.[1]

     

    In addition adverse press reports questioning the ethics of conducting this trial, which subsequently led to the involvement of politicians, further heightened these concerns. Despite the clearly demonstrated existence of clinical equipoise for adrenaline in cardiac arrest it remained impossible to change the decision not to participate.[1]

     

    What was the conclusion produced by the Jacobs study?
     

    CONCLUSION: Patients receiving adrenaline during cardiac arrest had no statistically significant improvement in the primary outcome of survival to hospital discharge although there was a significantly improved likelihood of achieving ROSC.[1]

     

    As the homeopaths put their spin on studies that do not really support their claims, people who do not understand science put similar spin on the results of this. For example, if you take a Bayesian approach[2], but distort it to mean that you give extra weight to everything that supports your belief and take away credit from everything else, you can claim that this is an example of science proving that epinephrine works.

    Another way of doing this is to claim that you don’t give the 1 mg dose of epinephrine, therefore the study does not apply to your patients. After all, you are just engaging in a poorly documented, unapproved study, which allows you to think of the survivors as examples of the drug working and make excuses for the rest. Of course, if you don’t give the 1 mg dose of epinephrine, is there any evidence that your treatment is safe or effective? No.

    Rather than insisting that this method of dosing patients be studied, in order to determine if it really is safe or if it really is effective at anything other than getting a pulse in a brain-dead body, claim to be ahead of the science.

    Why find out what is really best for the patients, when there are so many ways of declaring victory and running away?

    In 2018, we had the results of the next study of placebo vs. adrenaline (epinephrine in non-Commonwealth countries, but only Commonwealth countries have bothered to do the research). The conclusion was the same as the conclusion for the only previous study.
     

    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.[3]

     

    Has anyone else stated that the use of epinephrine should be limited to controlled trials?

    Not that I know of.

    Everyone else seems to be claiming that giving smaller boluses of epinephrine. or giving titrated infusions of epinephrine is different. Some claim that it is nihilism to refuse to believe in their slightly different treatment – at least until there is undeniable evidence of lack of benefit, or undeniable evidence of harm, or both.

    Requiring evidence of benefit, before using a treatment on a patient is being reasonable.

    Using inadequately studied treatments on people when they are at their most vulnerable is not good medicine.

    A doctor’s oath to Apollo does not include a requirement to perpetuate dogma, but medicine is only slowly starting to focus on what is best for patients, rather than what is best for appearances.

    Dr. Ryan Jacobsen addressed a similar dogma, when he got rid of the long spine board in the system where he was medical director. His description of the evidence applies to epinephrine (bolus, mini-bolus, infusion, patch, inhaler, down the tube, oral, whatever) –

    Other than historical dogma and institutional EMS medical culture we can find no evidence-based reason to continue to use the Long Spine board epinephrine as it currently exists in practice today.[4]

    I changed EMS to medical and the Long Spine board to epinephrine.

    We have good evidence that if your loved one is a laboratory pig, rat, dog, . . . we can kill them and get them back neurologically intact with epinephrine – and with other treatments that have been discarded because they do not have the same effect on humans as on lab animals.

    Let us treat your loved ones like the lab animals we think they are.

    Don’t use EBM (Evidence-Based Medicine), because belief is more important than reality.

    The world is a comedy to those that think; a tragedy to those that feel. – Horace Walpole.

    Keep thinking. Keep demanding evidence. After the nonsense being preached by the believers is exposed, we can improve the outcomes for our patients, because medicine is about doing what is best for the patient, and not about protecting the dogma.

    –

    Footnotes:

    –

    [1] Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial
    Jacobs IG, Finn JC, Jelinek GA, Oxer HF, Thompson PL.
    Resuscitation. 2011 Sep;82(9):1138-43. doi: 10.1016/j.resuscitation.2011.06.029. Epub 2011 Jul 2.
    PMID: 21745533

    Free Full Text PDF Download from semanticscholar.org

    –

    [2] Bayesian inference
    Wikipedia
    Article

    –

    [3] A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest.
    Perkins GD, Ji C, Deakin CD, Quinn T, Nolan JP, Scomparin C, Regan S, Long J, Slowther A, Pocock H, Black JJM, Moore F, Fothergill RT, Rees N, O’Shea L, Docherty M, Gunson I, Han K, Charlton K, Finn J, Petrou S, Stallard N, Gates S, Lall R; PARAMEDIC2 Collaborators.
    N Engl J Med. 2018 Aug 23;379(8):711-721. doi: 10.1056/NEJMoa1806842. Epub 2018 Jul 18.
    PMID: 30021076

    –

    [4] Johnson County EMS System Spinal Restriction Protocol 2014
    Ryan C. Jacobsen MD, EMT-P, Johnson County EMS System Medical Director
    Jacob Ruthsrom MD, Deputy EMS Medical Director
    Theodore Barnett MD, Chair, Johnson County Medical Society EMS Physicians Committee
    Johnson County EMS System Spinal Restriction Protocol 2014 in PDF format.

    .

    Filed Under: 'Alternative' Medicine, ACLS, Cardiac Arrest, Critical Judgment, EBM, Epinephrine, Ethics, Evidence, Heresy, Pharmacology, Research, Science

    Anti-Vaccine Means Pro-Corruption

    Fri, 30 Nov 2018 09:30:45 -0500 by
     

    Can you be opposed to vaccines and not be supporting corruption? What does it mean to oppose vaccines?

    Vaccines are probably the safest and most effective medical intervention available. Anti-vaxers oppose that.

    Vaccines save millions of lives every year. Anti-vaxers oppose that.

    If you disagree, provide valid evidence that anything else is as safe as vaccines and provide valid evidence that anything else is as effective as vaccines. There is the small possibility that I am wrong and that vaccines are only second, or maybe even third, among the safest and most effective medical interventions available.

    But aren’t the anti-vaxers trying to protect children from unnecessary risk?

    That is one of many anti-vaccine claims, but it is just another anti-vax lie.

    Look at these heroes of the anti-vaccine propaganda industry. Mark and David Geier.

    David Geier pretends to be a doctor, even though he never has been a doctor, or even been enrolled in a medical school.
     

    As explained above, the Board concludes that David Geier practiced medicine in Maryland without being licensed by the Board to practice in violation of section 14-601 of the Health Occupations Article.[1]

     

    Mark Geier did become a doctor, but the corruption of the anti-vax propaganda and treatment business led him to violate his responsibility to protect his patients. If you see Mark Geier working as a doctor, call the police.
     

    Since 2011, Geier’s medical license has been suspended or revoked in every state in which he was licensed over concerns about his autism treatments and his misrepresentation of his credentials to the Maryland Board of Health, where he falsely claimed to be a board-certified geneticist and epidemiologist.[4] [2]

     

    What is so bad about the Geiers and why do anti-vaxers continue to worship the Geiers?

    Mark and David Geier castrate children with a chemical that has been approved for some medical uses, but definitely not to treat autism. The chemical has never been shown to be safe or even slightly effective for that purpose. If you think that autism is the worst thing ever – worse than smallpox, measles, polio, pertussis, et cetera, you may think that it is morally acceptable to torture children and to have faith in these quacks.
     


     

    The fake doctor (David) is on the left and the revoked license doctor (Mark) is on the right.

    But isn’t it an exaggeration to call this chemical castration.
     

    Speaking about one teen he put on the drug, Mark Geier said: “I wasn’t worried about whether he would have children when he is 25 years old. If you want to call it a nasty name, call it chemical castration. If you want to call it something nice, say you are lowering testosterone.”[3]

     

    For those who claim that this would be a short-term treatment, and the side effects would be minimized, that’s not the way quacks work – especially with paying customers. These are not reasonable people. Quacks will be expected to keep giving the magic treatment, possibly increasing the dose several times, until that treatment works, because they think that they know believe that it works. Reasonable people would be expected to stop never start this unapproved and dangerous treatment to begin with. Since the treatment does not work, and is expected to make the patients’ conditions worse, these people would not be expected to stop. As with other alternative medicine, treatment failures are blamed on the patient, or on the family. Quacks do not take responsibility for the incompetence of using chemicals that are dangerous and ineffective.

    But what if it really does work?

    Almost every proposed treatment, regardless of what it is, will be found to be more harmful than beneficial. Most are discarded long before they get to the point of being tested on actual humans. Poisoning patients, based on What if it works? is dangerous, unethical, and irresponsible.

    If you have an autistic child, do not let the Geiers chemically castrate your child for fun and profit.

    How do the same anti-vaxers, who claim that they are protecting their children from what is probably the safest and most effective medical intervention available, support this dangerous, unethical, and irresponsible treatment?

    That is the way anti-vaxers think. Anti-vccine claims are arrogant rejections of competence, science, and reality. Protect your children from anti-vaxers.

    –

    Footnotes:

    –

    [1] In the matter of David A. Geier before the Maryland State Board of Physicians
    Case Nos. 2008-0022 & 2009-0318
    Maryland Department of Health
    Final Decision and Order in PDF format.

    –

    [2] Mark Geier
    Wikipedia
    Article

    –

    [3] ‘Miracle drug’ called junk science
    Trine Tsouderos
    Tribune reporter
    May 21, 2009
    Article

    .

    Filed Under: Anti-Science, Children, Conspiracy Theories, Corruption, Critical Judgment, Denialism, Evidence, Pharmacology, Research, Risk Management

    A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest – Part I

    Thu, 19 Jul 2018 14:40:46 -0400 by
     
    Also to be posted on ResearchBlogging.org when they relaunch the site.

    The results are in from the only completed Adrenaline (Epinephrine in non-Commonwealth countries) vs. Placebo for Cardiac Arrest study.
     


     

    Even I overestimated the possibility of benefit of epinephrine.

    I had hoped that there would be some evidence to help identify patients who might benefit from epinephrine, but that is not the case.

    PARAMEDIC2 (Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest) compared adrenaline (epinephrine) with placebo in a “randomized, double-blind trial involving 8014 patients with out-of-hospital cardiac arrest”.

    More people survived for at least 30 days with epinephrine, which is entirely expected. There has not been any controversy about whether giving epinephrine produces pulses more often than not giving epinephrine. As with amiodarone (Nexterone and Pacerone), the question has been whether we are just filling the ICUs and nursing home beds with comatose patients.
     

    There was no statistical evidence of a modification in treatment effect by such factors as the patient’s age, whether the cardiac arrest was witnessed, whether CPR was performed by a bystander, initial cardiac rhythm, or response time or time to trial-agent administration (Fig. S7 in the Supplementary Appendix). [1]

     

    The secondary outcome is what everyone has been much more interested in – what are the neurological outcomes with adrenaline vs. without adrenaline?

    The best outcome was no detectable neurological impairment.
     

    the benefits of epinephrine that were identified in our trial are small, since they would result in 1 extra survivor for every 112 patients treated. This number is less than the minimal clinically important difference that has been defined in previous studies.29,30 Among the survivors, almost twice the number in the epinephrine group as in the placebo group had severe neurologic impairment.

    Our work with patients and the public before starting the trial (as summarized in the Supplementary Appendix) identified survival with a favorable neurologic outcome to be a higher priority than survival alone. [1]

     


    Click on the image to make it larger.
     

    Are there some patients who will do better with epinephrine than without?

    Maybe (I would have written probably, before these results), but we still do not know how to identify those patients.

    Is titrating tiny amounts of epinephrine, to observe for response, reasonable? What response would we be looking for? Wat do we do if we observe that response? We have been using epinephrine for over half a century and we still don’t know when to use it, how much to use, or how to identify the patients who might benefit.

    I will write more about these results later

    We now have evidence that, as with amiodarone, we should only be using epinephrine as part of well controlled trials.

    –

    Also see –

    How Bad is Epinephrine (Adrenaline) for Cardiac Arrest, According to the PARAMEDIC2 Study?

    –

    Footnotes:

    –

    [1] A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest.
    Perkins GD, Ji C, Deakin CD, Quinn T, Nolan JP, Scomparin C, Regan S, Long J, Slowther A, Pocock H, Black JJM, Moore F, Fothergill RT, Rees N, O’Shea L, Docherty M, Gunson I, Han K, Charlton K, Finn J, Petrou S, Stallard N, Gates S, Lall R; PARAMEDIC2 Collaborators.
    N Engl J Med. 2018 Jul 18. doi: 10.1056/NEJMoa1806842. [Epub ahead of print]
    PMID: 30021076

    Free Full Text from NEJM

    All supplementary material is also available at the end of the article at the NEJM site in PDF format –

    Protocol

    Supplementary Appendix

    Disclosure Forms

    There is also an editorial, which I have not yet read, by Clifton W. Callaway, M.D., Ph.D., and Michael W. Donnino, M.D. –

    Testing Epinephrine for Out-of-Hospital Cardiac Arrest.
    Callaway CW, Donnino MW.
    N Engl J Med. 2018 Jul 18. doi: 10.1056/NEJMe1808255. [Epub ahead of print] No abstract available.
    PMID: 30021078

    Free Full Text from NEJM

    .

    Filed Under: 2018 ACLS Guidelines, ACLS, Common Sense, Critical Judgment, Drug Shortages, Epinephrine, Ethics, Evidence, Heresy, Intubation, Lasix, Mythology, Narrative Fallacy, Oxygen, Pharmacology, Placebo, Potentially Reversible Causes, Probability, Research, Research Blogging, Resuscitation Theater, tPA
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