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

- Rogue Medic

What’s the Good News on Hydroxychloroquine?

Hydroxychloroquine is a darling of the media and of politicians, but what about the evidence? Well, the evidence on the use of hydroxychloroquine to treat humans with COVID-19 (COronaVIrus Disease identified in 2019) is either negative (hydroxychloroquine is worse than homeopathy, acupuncture, naturopathy, prayer, . . . ) or the evidence is neutral (hydroxychloroquine is just as useless as homeopathy, acupuncture, naturopathy, prayer, . . . ).


But what is the good news?


The good news is that all of the research on hydroxychloroquine is of low quality or of very low quality. This is exactly the kind of evidence that frauds use to sell their fly by night panaceas.


The “best” news for the frauds is that one study showing harm from hydroxychloroquine has been retracted by most of the authors, due to problems with the data.[1],[2] The researchers contracted out the data acquisition and analysis to Surgisphere Corporation, a private company that appears to have promised to be able to deliver more than it can deliver.


If the negative paper has been retracted, why am I calling the promoters of hydroxychloroquine the frauds?


I am not referring to any of the researchers as frauds, not even the ones from the company that provided the retracted information. The frauds are the people promoting hydroxychloroquine without any evidence that hydroxychloroquine is safe or effective to treat COVID-19 in our species. These people are recklessly and irresponsibly endangering people for their own apparently political reasons.


We still do not have any valid evidence that hydroxychloroquine is safe to use in any humans to treat COVID-19.


We still do not have any valid evidence that hydroxychloroquine is effective at improving any outcomes for any humans with COVID-19.


Experimentation on humans should be limited to well controlled research studies.


The WHO (World Health Organization) appropriately, and only temporarily, paused research on hydroxychloroquine to re-examine the safety data available. The enrollment of patients in the WHO research has resumed.[3]


For those who claim that this retraction is evidence that science doesn’t work – It is amusing to see you trying to cite evidence to support your rejection of evidence, every time you do it. May you never tire of demonstrating the validity of the Dunning-Kruger effect.


This is like using a stopped clock to tell you the time. The stopped clock does not provide any useful information about the actual time, but it does provide useful information about the person claiming it provides useful information about the time.



This was pre-print – not yet peer reviewed, which was retracted by most of the authors, because of questions raised about the data. It may turn out that the outcomes for patients were better than represented in the paper. It may turn out that the outcomes for patients were the same as than represented in the paper. It may turn out that the outcomes for patients were worse than represented in the paper. We won’t know until the full information is independently analyzed, which might not happen. The failure to provide access for independent analysis was the reason for the retraction.


Late addition (6/08/2020 at 15:08): Dr. Steven Novella has a more detailed description of this at Neurologica, written on 6/08/2020 after I posted this on 6/06/2020:


The Surgisphere Fiasco



Footnotes:


[1] Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis.
Mehra MR, Desai SS, Ruschitzka F, Patel AN.
Lancet. 2020 May 22:S0140-6736(20)31180-6. doi: 10.1016/S0140-6736(20)31180-6. Online ahead of print.
PMID: 32450107


Free Full Text from PubMed Central.


[2] Retraction—Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis
Mandeep R Mehra, Frank Ruschitzka, Amit N Patel
Published:June 05, 2020
DOI:https://doi.org/10.1016/S0140-6736(20)31324-6


[3] “Solidarity” clinical trial for COVID-19 treatments
WHO (World Health Organization)
Information page.


Update on hydroxychloroquine


Originally posted 27 May 2020, updated 4 June 2020


Having met on 23 May 2020, the Executive Group of the Solidarity Trial decided to implement a temporary pause of the hydroxychloroquine arm of the trial, because of concerns raised about the safety of the drug. This decision was taken as a precaution while the safety data were reviewed by the Data Safety and Monitoring Committee of the Solidarity Trial.


On 3 June 2020, WHO’s Director-General announced that on the basis of the available mortality data, the members of the committee have recommended that there are no reasons to modify the trial protocol.


The Executive Group received this recommendation and endorsed the continuation of all arms of the Solidarity Trial, including hydroxychloroquine.


The Data Safety and Monitoring Committee will continue to closely monitor the safety of all therapeutics being tested in the Solidarity Trial.



.

Hydroxychloroquine – The More You Know, The Worse It Looks



Do you want to use a drug that was never based on any good evidence, but only a hunch? Try hydroxychloroquine. The president says, What have you got to lose?


Kitchen sink medicine is a remnant of the Dark Ages, but it has not been eliminated from medicine. It is the argument from ignorance. If you can’t prove that the treatment is harmful, the treatment is wonderful. If you can prove the treatment is harmful, you are part of a conspiracy.


This is further evidence that hydroxychloroquine is harmful. The higher the quality of the evidence about hydroxychloroquine, the worse hydroxychloroquine looks.


Today, Lancet published this study comparing almost 15,000 patients receiving several different experimental treatments with about 80,000 patients not receiving any of the experimental treatments. This should convince reasonable people that there is no justification for treating patients with hydroxychloroquine outside of a well controlled randomized trial.


The comments on articles about the study are full of the usual anti-science, anti-vax, alternative medicine propaganda. Their religion has failed, but they keep preaching.


After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9·3%), hydroxychloroquine (18·0%; hazard ratio 1·335, 95% CI 1·223–1·457), hydroxychloroquine with a macrolide (23·8%; 1·447, 1·368–1·531), chloroquine (16·4%; 1·365, 1·218–1·531), and chloroquine with a macrolide (22·2%; 1·368, 1·273–1·469) were each independently associated with an increased risk of in-hospital mortality.[1]


The evidence shows that you are twice as likely to die if you receive hydroxychloroquine.


Don’t listen to anti-science, anti-vax, anti-medicine preachers, because they are not interested in your health.


What have you got to lose?


What are you treating, you politics/religion or your health?


If your goal is to treat your religion, go ahead and use the magic elixir and maybe you will not be harmed by it.


If your goal is to treat your health, avoid magic claims about treatments, regardless of the treatment. Use treatments that work in the real world.


What have you got to lose?


You are twice as likely to lose your life. Among survivors, the significant adverse effect rate was much higher in the hydroxychloroquine groups. This is the highest quality research so far and there is no good news for the hydroxychloroquine.


Read the full paper and think for yourself. Don’t listen to those making excuses to promote their agenda. Your health has never been important to those who reject science.


It is unfortunate that we do not have some treatment that works well, but that is not a good reason to bet your life on bad medicine. More people survive with better health with conventional treatment.



Footnotes:


[1] Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis
Prof Mandeep R Mehra, MD, Sapan S Desai, MD, Prof Frank Ruschitzka, MD, Amit N Patel, MD
Lancet. Published:May 22, 2020
DOI:https://doi.org/10.1016/S0140-6736(20)31180-6


Free Full Text from Lancet.


.

Interim Guidance for Basic and Advanced Life Support in Adults, Children, and Neonates With Suspected or Confirmed COVID-19 – April 9, 2020

All of the revised guidelines are at the end.

Treatment of cardiac arrest in the time of a pandemic requires changes to the ACLS (Advanced Cardiac Life Support), PALS (Pediatric Advanced Life Support), and NRP (Neonatal Resuscitation Program) guidelines. These were written specifically for COVID-19, but would apply just as well to any other pandemic with the possibility of aerosolized respiratory transmission.

Who is making these recommendation?

From the Emergency Cardiovascular Care Committee and Get With the Guidelines®-Resuscitation Adult and Pediatric Task Forces of the American Heart Association in Collaboration with the American Academy of Pediatrics, American Association for Respiratory Care, American College of Emergency Physicians, The Society of Critical Care Anesthesiologists, and American Society of Anesthesiologists: Supporting Organizations: American Association of Critical Care Nurses and National EMS Physicians[1]

Why are these recommendations being made?

Hypoxemic respiratory failure secondary to acute respiratory distress syndrome (ARDS), myocardial injury, ventricular arrhythmias, and shock are common among critically ill patients and predispose them to cardiac arrest,5-8 as do some of the proposed treatments, such as hydroxychloroquine and azithromycin, which can prolong the QT.9 With infections currently growing exponentially in the United States and internationally, the percentage of cardiac arrests with COVID-19 is likely to increase.

Healthcare workers are already the highest risk profession for contracting the disease.10 This risk is compounded by worldwide shortages of personal protective equipment (PPE). Resuscitations carry added risk to healthcare workers for many reasons. First, the administration of CPR involves performing numerous aerosol-generating procedures, including chest compressions, positive pressure ventilation, and establishment of an advanced airway. During those procedures, viral particles can remain suspended in the air with a half-life of approximately 1 hour and be inhaled by those nearby.11 Second, resuscitation efforts require numerous providers to work in close proximity to one another and the patient. Finally, these are high-stress emergent events in which the immediate needs of the patient requiring resuscitation may result in lapses in infection-control practices.[1]

Will the changes decrease chances of successful resuscitation?

Yes. That is unavoidable, but DNRs (Do Not Resuscitate orders) and POLSTs (Physicians Orders for Life Sustaining Treatment) also decrease the chances of successful resuscitation. These changes are still the right thing to do.

How do these changes decrease the chances of successful resuscitation?

There is more focus on successful intubation – at the expense of continuous chest compressions. Chest compressions definitely improve outcomes, while there is no evidence that intubation improves outcomes – and there is evidence that intubation decreases successful resuscitation.

Prioritize oxygenation and ventilation strategies with lower aerosolization risk

● Use a HEPA filter, if available, for all ventilation
● Intubate early with a cuffed tube, if possible, and connect to mechanical ventilator, when able
● Engage the intubator with highest chance of first-pass success
● Pause chest compressions to intubate
● Consider use of video laryngoscopy, if available
● Before intubation, use a bag-mask device (or T-piece in neonates) with a HEPA filter and a
tight seal
● For adults, consider passive oxygenation with nonrebreathing face mask as alternative to bagmask device for short duration
● If intubation delayed, consider supraglottic airway
● Minimize closed circuit disconnections[1]

The AHA is now telling us to stop compressions to help minimize the number of intubation attempts, but not because intubation is going to improve outcomes for the patient. This is to protect everyone near the patient from aerosolized infectious material. An endotracheal tube with a HEPA filter is not an absolute protection, but intubation with a HEPA filter is probably best at preventing spread of aerosolized infectious material than other methods of ventilation and probably even better than passive ventilation (compression only resuscitation with a mask over the patient’s mouth).

Because our patients will now have a lower chance of a good outcome (being resuscitated with good brain function), we should also be more selective about whom we attempt to resuscitate. Too many of us have only been going through the motions, because we have refused to recognize futility, or our medical directors have refused to let us recognize futility.

Even though this lower chance of a good outcome is still better than before we focused on chest compressions, more patients should not have resuscitation attempted.

Consider resuscitation appropriateness

● Address goals of care
● Adopt policies to guide determination, taking into account patient risk factors for survival [1]

The other import consideration is the transport of family members.

Transport

o Family members and other contacts of patients with suspected or confirmed COVID-19 should not ride in the transport vehicle.
o If return of spontaneous circulation (ROSC) has not been achieved after appropriate resuscitation efforts in the field, consider not transferring to hospital given the low likelihood of survival for the patient,17 balanced against the added risk of additional exposure to prehospital and hospital providers.[1]

Unfortunately, footnote 17 is to page 16 of CARES (the Cardiac Arrest Registry to Enhance Survival), which is about using CARES in Ohio. I suspect that this was meant to refer to something else, so the wrong citation was provided in the rush to get new guidelines on line quickly.

17. CARES: Cardiac Arrest Registry to Enhance Survival. 2018 Annual Report.

https://mycares.net/sitepages/uploads/2019/2018_flipbook/index.html?page=16



Below are all of the new AHA algorithms (they are also available in PDF format at
https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.047463



AHA – COVID-19 Recommendations – BLS Healthcare Provider Adult Cardiac Arrest Algorithm [1]

Click on the image for full size.



AHA – COVID-19 Recommendations – ACLS Cardiac Arrest Algorithm [1]

Click on the image for full size.



AHA – COVID-19 Recommendations – BLS Healthcare Provider Pediatric Cardiac Arrest Algorithm for 2 or More Rescuers [1]

Click on the image for full size.



AHA – COVID-19 Recommendations – BLS Healthcare Provider Pediatric Cardiac Arrest Algorithm for the Single Rescuer [1]

Click on the image for full size.



AHA – COVID-19 Recommendations – PALS Pediatric Cardiac Arrest Algorithm [1]

Click on the image for full size.



Footnotes:



[1] Interim Guidance for Basic and Advanced Life Support in Adults, Children, and Neonates With Suspected or Confirmed COVID-19: From the Emergency Cardiovascular Care Committee and Get With the Guidelines®-Resuscitation Adult and Pediatric Task Forces of the American Heart Association in Collaboration with the American Academy of Pediatrics, American Association for Respiratory Care, American College of Emergency Physicians, The Society of Critical Care Anesthesiologists, and American Society of Anesthesiologists: Supporting Organizations: American Association of Critical Care Nurses and National EMS Physicians.
Edelson DP, Sasson C, Chan PS, Atkins DL, Aziz K, Becker LB, Berg RA, Bradley SM, Brooks SC, Cheng A, Escobedo M, Flores GE, Girotra S, Hsu A, Kamath-Rayne BD, Lee HC, Lehotzky RE, Mancini ME, Merchant RM, Nadkarni VM, Panchal AR, Peberdy MAR, Raymond TT, Walsh B, Wang DS, Zelop CM, Topjian A.
Circulation. 2020 Apr 9. doi: 10.1161/CIRCULATIONAHA.120.047463. [Epub ahead of print]
PMID: 32270695

Free Full Text from the American Heart Association in PDF format

This page is the abstract from the American Heart Association. It has a tab for PDF/EPUB, but the link only provides the PDF link above.



.

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

   

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.

  –  

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  

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.

  –  

[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.

  –  

[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.

  –  

[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    

.

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

 

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.

    [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

    .

    ACLS Excuses for Causing Harm with Epinephrine

     

    The next ACLS guidelines are available for review and comment, before they are finalized. The Consensus on Science with Treatment Recommendations (CoSTR) from the International Liaison Committee on Resuscitation (ILCOR) are available for two guidelines:

    Vasopressors in Adult Cardiac Arrest

    Advanced Airway Management During Adult Cardiac Arrest

    We have been using these interventions for so long, that there should be great evidence to show that benefits and harms of both interventions, but there is no good evidence to support either intervention.

    For epinephrine (adrenaline in Commonwealth countries), the most commonly used vasopressor and the only one rally being considered, there is no evidence of actual benefit – increased survival without severe brain damage.

    Nothing else matters.

    There is no valid evidence that increasing any surrogate endpoint improves survival without severe brain damage. The evidence cited by ILCOR shows that epinephrine increases the rate of severe brain damage.
     

    Intervention: Vasopressor or a combination of vasopressors provided intravenously or intraosseously during cardiopulmonary resuscitation.[1]

     

    Here are the outcomes that are supposed to indicate that the patient is better.
     

    Outcomes: Short-term survival (return of spontaneous circulation (ROSC) and survival to hospital admission), mid-term survival (survival to hospital discharge, 28 days, 30 days, or 1 month), mid-term favorable neurological outcomes (Cerebral Performance Category score of 1-2 or modified Rankin Scale 0-3 at hospital discharge, 28 days, 30 days, or 1 month) and long-term favorable and poor (modified Rankin Score 4-5) neurological outcomes (after 1 month).[1]

     

    Is ROSC an improvement?

    We aren’t supposed to ask that question. These are faulty assumption that the guidelines are based on.

    1. Doing something more is better than only doing things supported by valid evidence of improved survival without severe brain damage.

    No.

    How much harm is being caused in this rush to get a pulse back?

    We are supposed to ignore our understanding of research, look at a statistically insignificant “trend”, and extrapolate that statistically insignificant “trend” to support the prejudice that our intervention has not been harmful.

    That is not good science.

    That is not good medicine.
     

    Why aren’t there any studies large enough to show improved survival without severe brain damage for anything other than rapid defibrillation (when indicated VF/pulseless VT) and chest compressions?

    The research has only produced excuses and surrogate endpoint. Surrogate endpoints are for hypothesis generation and sales pitches to the least knowledgeable, but not for treatment guidelines.

    ILCOR has told us this before, but that was because the choice was between large doses of epinephrine and small doses of epinephrine, not between epinephrine and no epinephrine.

    The choice is the same.

    Is the more aggressive intervention helping?

    The answer is the same. No. That is not the conclusion of the evidence.
     

    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 goal is a pulse with more severe brain damage, then epinephrine is the way to go.

    If the goal is increased survival without severe brain damage, we have to keep looking.

    We should limit the use of epinephrine to well controlled research until there is evidence of improvement in outcomes that matter.

    If this evidence is never found, our patients will not have been harmed by epinephrine.

    If this evidence is eventually found, it is something that should have been insisted on decades ago. We should not use wishful thinking and surrogate endpoints to justify interventions that harm patients.

    We used to stop compressions to let the medic/nurse/doctor intubate, or start an IV (IntraVenous) line.

    We knew that the tube was more important.

    We knew that the drugs given through the IV line were more important.

    The 2005 guidelines told us to continue compressions during intubation and during IV attempts and to improve the quality of the compressions.

    That focus on high quality compressions is the only time we have improved outcomes that matter.
     

    CONCLUSIONS: Compared with controls, patients with out-of-hospital cardiac arrest treated with a renewed emphasis on improved circulation during CPR had significantly higher neurologically intact hospital discharge rates.[3]

     

    33 1/3% vs 60% increased survival without severe brain damage.
     

    In 2004, we began a statewide program to advocate chest compression-only CPR for bystanders of witnessed primary OHCA. Over the next five years, we found that survival of patients with a shockable rhythm was 17.7% in those treated with standard bystander CPR (mouth-to-mouth ventilations plus chest compression) compared to 33.7% for those who received bystander chest-compression-only CPR.[4]

     

    18% vs 34% increased survival only – not increased survival without severe brain damage.
     

    In the analysis of MICR [Minimally Interrupted Cardiac Resuscitation] protocol compliance involving 2460 patients with cardiac arrest, survival was significantly better among patients who received MICR than those who did not (9.1% [60/661] vs 3.8% [69/1799]; OR, 2.7; 95% CI, 1.9-4.1), as well as patients with witnessed ventricular fibrillation (28.4% [40/141] vs 11.9% [46/387]; OR, 3.4; 95% CI, 2.0-5.8).[5]

     

    9% vs 4% increased survival only – not increased survival without severe brain damage.
     

    Neurologic outcomes were also better in the patients who received CCR (OR=6.64, 95% CI=1.31 to 32.8).[6]

     

    6 2/3 more likely to have increased survival without severe brain damage. The range is 1 1/3 to almost 33 times, because of the small numbers, but unlike epinephrine, this is statistically significant and supported by other research.

    We are still making excuses for using a drug that causes harm and does not appear to provide a benefit that is greater than the harm. If there is more benefit, it is too small to be measured, even in a study with over 9,000 patients. We do not know which patients benefit and which patients are harmed, so we do not know how to minimize the harm that we cause.

    Our patients deserve better.

    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.

    [3] Implementing the 2005 American Heart Association Guidelines improves outcomes after out-of-hospital cardiac arrest.
    Aufderheide TP, Yannopoulos D, Lick CJ, Myers B, Romig LA, Stothert JC, Barnard J, Vartanian L, Pilgrim AJ, Benditt DG.
    Heart Rhythm. 2010 Oct;7(10):1357-62. doi: 10.1016/j.hrthm.2010.04.022. Epub 2010 Apr 24.
    PMID: 20420938

    Free Full Text from Heart Rhythm.

    [4] The cardiocerebral resuscitation protocol for treatment of out-of-hospital primary cardiac arrest.
    Ewy GA.
    Scand J Trauma Resusc Emerg Med. 2012 Sep 15;20:65. doi: 10.1186/1757-7241-20-65. Review.
    PMID: 22980487

    Free Full Text from PubMed Central.

    [5] Minimally interrupted cardiac resuscitation by emergency medical services for out-of-hospital cardiac arrest.
    Bobrow BJ, Clark LL, Ewy GA, Chikani V, Sanders AB, Berg RA, Richman PB, Kern KB.
    JAMA. 2008 Mar 12;299(10):1158-65. doi: 10.1001/jama.299.10.1158.
    PMID: 18334691

    Free Full Text from JAMA.

    [6] Cardiocerebral resuscitation is associated with improved survival and neurologic outcome from out-of-hospital cardiac arrest in elders.
    Mosier J, Itty A, Sanders A, Mohler J, Wendel C, Poulsen J, Shellenberger J, Clark L, Bobrow B.
    Acad Emerg Med. 2010 Mar;17(3):269-75. doi: 10.1111/j.1553-2712.2010.00689.x.
    PMID: 20370759

    Free Full Text from Acad Emerg Med.

    .

    Protecting Systemic Incompetence – Part I

     

    We demand the lowest standards, because we are willfully ignorant and we do not want to understand. The surprise is that so many of us survive our devotion to incompetence. The loudest voices tend to dominate the discussions and the loudest voices demand that their excuses for incompetence be accepted. The rest of us don’t oppose incompetence enough.

    A nurse was told to give 2 mg Versed (the most common brand of midazolam in the US) for sedation for a scan, intended to give 1 mg Versed, but actually gave an unknown quantity of vecuronium (Norcuron is the most common brand in the US). The patient was observed to be unresponsive and pulseless by the techs in the scan. A code was called. The family learned the details from a newspaper article, not from the hospital.
     

    A Tennessee nurse charged with reckless homicide after a medication error killed a patient pleaded not guilty on Wednesday in a Nashville courtroom packed with other nurses who came in scrubs to show their support.[1]

     

    The nurse intended to give a medication that should be limited to patients who are monitored (ECG and waveform capnography), because different patients will respond in different ways. This is basic drug administration and deviation from that basic competence may even have been common in this Neuro ICU (Neurological Intensive Care Unit). We demand low standards, because we do not want to understand.

    We don’t need to monitor for that, because that almost never happens.

    Except these easily preventable errors do happen. And we lie about it. We help to cover it up, because we demand low standards, regardless of how many patients have to suffer for the benefit of our incompetence.

    This is a common argument used by doctors, nurses, paramedics, . . . . It makes no sense, but we keep demonstrating that we don’t care.

    The people in charge should act responsibly, but they delegate responsibility and we reward them.

    Back to the hospital, Vanderbilt University Medical Center (VUMC) is a university medical center, so the standards should be high. VUMC was founded in 1874 and is ranked as one of the best hospitals in America.

    There is a drug dispensing machine, from which less-than-killed nurses can obtain almost anything and administer almost anything, without understanding enough to recognize the problem. This is an administrative problem. This was designed by someone with no understanding of risk management.

    The over-ride of the selection is not the problem, because emergencies happen and it is sometimes necessary to bypass normal procedures during an emergency. Ambulances are equipped with lights, sirens, and permission to violate certain traffic rules for this reason.

    Some of the many blatant problems are:

    * The failure of the nurse to have any understanding of the medication supposed to be given

    * The failure of the nurse to recognize that the drug being given was not the drug ordered.

    * The failure of the nurse to monitor the patient being given a drug for sedation.

    * Most of all, the failure of the hospital – the nurses, the doctors, the administrators, to try to make sure that at least these minimum standards are in place.

    * How often do nurses in the Neuro ICU give midazolam?

    * Why is a nurse, who is clearly not familiar with midazolam, giving midazolam to any patient?

    * How is a nurse, working unsupervised in a Neuro ICU not familiar with midazolam?

    * What kind of qualifications are required for a nurse to give sedation without supervision?

    * Since this nurse was orienting another nurse, what qualifies this nurse to orient anyone?

    * Given the side effects of midazolam, why was midazolam ordered without monitoring?

    * Given the side effects of midazolam, was it the most appropriate sedative for use in a setting where monitoring is going to be difficult?

    * Was it the more rapid onset of sedation, in order to free up the PET scan more quickly and/or avoid having to reschedule the scan, that led to the choice of midazolam?

    * How well do any of the doctors understand the pharmacology of midazolam if they are giving orders for a nurse to grab a dose, take it down to the scan, give the drug, and return to the unit, abandoning the monitoring of the patient to the techs in the PET scan?

    * This is not a criticism of the techs in PET scan, but are techs authorized to manage sedated patients?

    * Even though they will often scan sedated patients, are the techs required to demonstrate any competence at managing sedated patients?
     

    The nurses being oriented apparently thought that it is customary to give sedation:

    1. without even looking at the name of the medication

    2. without confirming by looking at the name again, it before administration

    3. without double checking with a nurse, or tech, that the label matches the name of the drug to be given
     

    How many of the doctors, responsible for the care of ICU patients, would agree to be sedated, without being monitored, and to have their care handed off to PET scan technicians?

    Why didn’t the doctors and nurses see this as a problem before it made the news?

    If the problems were reported, nothing appears to have been done to address the problems beyond the usual – Nothing to see here. Move along. or That’s above your pay grade.

    That is the primary point I am trying to make.

    The problem is well above the pay grade of the nurse.
     

    Here is the part that experienced nurses have jumped on immediately:

    Why did the nurse think that midazolam needs to be reconstituted?

    Vecuronium (most common brand name is Norcuron) is a non-depolarizing neuromuscular-blocker, which comes as a poweder, that needs to be reconstituted.
     


    Image source
     

    1. Read label instructions?

    This nurse has repeatedly demonstrated a need to be supervised, but those responsible for that supervision have apparently ignored their responsibilities in a way that far exceeds any failures by this nurse.

    Is it possible that this is a one time event and that the nurse has behaved in an exemplary manner at all times while around doctors and other nurses before this day? It is possible, but the number and severity of the failures on the part of the nurse strongly suggest a pattern of not understanding, not caring, or both. I suspect that any lack of caring is due to a lack of understanding, because I have not yet lost all hope in humanity.

    Footnotes:

    [1] Nurse charged in fatal drug-swap error pleads not guilty
    By Travis Loller
    February 20, 2019
    Associated Press
    Article

    .

    This Rhythm is Hilarious

     


    Click on the image to make it larger.
     

    Apparently, the second 12 lead was after 150 mg of amiodarone. The hilarity is the amiodarone.

    I received this in an email. It is reported to have been posted on Facebook, but I choose not to have access to Facebook, so I do not have any more details. I am occasionally tempted to set up an account again, but I generally prefer intentional comedy.

    Everything you need to know is in the first 12 lead.

    Things that do not matter:

    Distance to the hospital.

    Time of onset.

    Last meal.

    National Registry certification.

    Et cetera.

    .