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

- Rogue Medic

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.


.

NIH clinical trial of remdesivir to treat COVID-19 begins

     

The University of Nebraska Medical Center (UNMC) in Omaha is the receiving facility for Americans repatriated with suspicion of infection with COVID-19 (COronaVIrus Disease 2019). UNMC will be enrolling patients in a double-blind study comparing standard treatment with an investigational antiviral drug against standard treatment with a placebo.[1]

The start of this study does not mean that anyone knows, or even has has good reason to believe, that remdesivir is an effective treatment in humans for COVID-19. Remdesivir is an investigational antiviral that has been tested on other coronaviruses, but has not been shown to be effective in treating humans. Remdesivir was also studied as a possible treatment for ebola virus (a filovirus), and was found to be effective in other species, but was not found to be effective in humans.
 

About Remdesivir Remdesivir is an investigational nucleotide analog with broad-spectrum antiviral activity – it is not approved anywhere globally for any use. Remdesivir has demonstrated in vitro and in vivo activity in animal models against the viral pathogens MERS and SARS, which are also coronaviruses and are structurally similar to COVID-19. The limited preclinical data on remdesivir in MERS and SARS indicate that remdesivir may have potential activity against COVID-19.

This is an experimental medicine that has only been used in a small number of patients with COVID-19 to date, so Gilead does not have an appropriately robust understanding of the effect of this drug to warrant broad use at this time.[2]
 

What is the most common symptom?

There does not appear to be any symptom that is always present.

Travel to China, or to the region of China where COVID-19 was first identified, or contact with people who were in contact with people known to be infected with COVID-19 are often present, but not always. Cough and fever appear to be the most common symptoms, but that are also not always present.

The full text of the first case in the US is worth reading.[3] A 35 year old male with a cough and no fever (37.2°C – 99.0°F), but he felt like he had a fever, went to an urgent care clinic, based on his symptoms and news reports. He did not test positive for anything else that is screened for. A sample was sent to the CDC (Centers for Disease Control and Prevention). He was treated with a variety of medications. A day after he was treated with remdesivir, he began to improve. Was he just getting better on his own? We do not know, but the research at UNMC should help to answer that question. Given the number of patients, and the already known distribution of patients, there should be plenty of participants, unless someone decides to promote the political witchcraft of “compassionate use”.[4] Then we may never know and remdesivir could become the blood-letting of the 21st century.

Footnotes:

[1] NIH clinical trial of remdesivir to treat COVID-19 begins Study enrolling hospitalized adults with COVID-19 in Nebraska.
Tuesday, February 25, 2020
National Institutes of Health (NIH)
News release

and –

NIH Clinical Trial of Remdesivir to Treat COVID-19 Begins Study Enrolling Hospitalized Adults with COVID-19 in Nebraska February 25, 2020
National Institute of Allergy and Infectious Diseases (NIAID)
News release

[2] COVID-19 Gilead Sciences Update On The Company’s Ongoing Response To COVID-19
Gilead Sciences
Article

[3] First Case of 2019 Novel Coronavirus in the United States.
Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, Spitters C, Ericson K, Wilkerson S, Tural A, Diaz G, Cohn A, Fox L, Patel A, Gerber SI, Kim L, Tong S, Lu X, Lindstrom S, Pallansch MA, Weldon WC, Biggs HM, Uyeki TM, Pillai SK; Washington State 2019-nCoV Case Investigation Team.
N Engl J Med. 2020 Jan 31. doi: 10.1056/NEJMoa2001191. [Epub ahead of print]
PMID: 32004427

Free Full Text from N Engl J Med.

[4] “Right to try” laws create tremendous legal uncertainties; FDA expanded access preferable The Goldwater Institute and the Kochs pushed “right to try” laws in an attempt to get rid of FDA oversight of access to investigational drugs. Instead, they created tremendous legal uncertainties, making the FDA’s expanded access program preferable for all.
Jann Bellamy
January 17, 2019
Science-Based Medicine
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.

.

Vaccines are probably the safest and most effective medical intervention available, so why do anti-vaxers lie about them

 

Why does anyone lie?

Anti-vaxers lie for the same reason as other people – for personal benefit.

Many anti-vaxers claim that there is an international conspiracy of doctors and researchers, as if all of the doctors and researchers, or even the pediatric doctors and researchers, in the world could agree on much of anything. When you realize how ridiculously large this conspiracy would be, how much a doctor or researcher would gain from providing valid information to expose such a conspiracy, and how aggressively law enforcement would punish those behind such a conspiracy, you understand the use of ridiculous is appropriate as a description of the conspiracy theory.

This is just another example of some people thinking they know more than everyone else, based on a lack of understanding. This feeds the over-inflated egos of anti-vaxers.

The smallpox vaccine has saved hundreds of millions of lives. Anti-vaxers opposed the smallpox vaccine and delayed the eradication of smallpox. Anti-vaxers helped smallpox kill people..

Our children are no longer vaccinated against smallpox, because smallpox has been wiped out by vaccines. Millions of children’s lives, and adult lives, are saved every year by the smallpox vaccine, without even giving it to children, because enough people rejected the lies of anti-vaxers.

Vaccines continue to save millions of lives every year, in spite of opposition by anti-vaxers.

There is plenty of research showing that vaccines are effective and safe, but to give the single clearest example of the benefit of vaccines, look at the following paper from JAMA. The Journal of the American Medical Association is one of the most respected medical publications in the world. Use any search engine to find a list of the most respected medical journals and you will find JAMA near the top.

Look at the decrease in the rates of illness and the rates of death for each vaccine-preventable illness after the introduction of the vaccine for that illness. Click on the image for a larger, easier to read version.
 


 

Table 1. Historical Comparison of Morbidity and Mortality for Vaccine-Preventable Diseases With Vaccines Licensed or Recommended Before 1980: Diphtheria, Measles, Mumps, Pertussis, Poliomyelitis, Rubella, Smallpox, Tetanusa [1]

 

This information has been simplified for those not comfortable with scientific research (I do not know the source of the image, it was not part of the paper in JAMA):
 


 

As you can see, these diseases are almost never a problem in America, where vaccination rates are still pretty high, although anti-vaxers are causing more and more outbreaks of diseases we had not seen in decades.

Some anti-vaxers will claim that the vaccines didn’t get rid of these diseases. These anti-vaxers claim that improved sanitation, improved hygiene, and improved diet got rid of these diseases. While these improvements are helpful, here is why that is just another anti-vax lie.

We have outbreaks of vaccine-preventable illnesses in America, when the rate of vaccination drops, even though sanitation, hygiene, and diet did not deteriorate. Yes, many of our diets are getting worse, but that is not what is causing outbreaks of whooping cough, measles, and other vaccine-preventable illnesses.

The rates of illness and death only have a dramatic change for each of the vaccine-preventable illnesses after the introduction of each vaccine. If sanitation, hygiene, and diet were the reasons, the illnesses would all start to go away at the same time, although not necessarily at the same rate. If that were the case, the decreases in these diseases could easily be shown to be due to improvements in sanitation, hygiene, and diet, but that is not the case.

Anti-vaxers cannot explain that, but anti-vaxers are not reasonable.
 

Why has the polio vaccine been so effective in India, when India has widespread problems with sanitation, hygiene, and diet?

Here is what the authors wrote:
 

India, a vastly diverse country with a 27 million birth cohort, undertook the largest vaccination drive against WPV (Wild Polio Virus) in the world. With high population density, poor civic infrastructure, poor sanitation, an almost nonexistent public health system, rampant malnutrition and diarrhea, difficult-to-reach locales, high population mobility, and extremely high force of WPV transmission in few states,3 the interruption of WPV transmission was extremely difficult and demanding. The interplay of these challenging factors provided a perfect milieu for the WPV to circulate, and the prospect of achieving zero-polio status seemed insurmountable.[2]

 

India completed a full 5 years as a “polio-free nation” on January 13, 2016.1 It was a remarkable feat considering the odds against achieving this status. [2]

Anti-vaxers will make excuses, but this clearly exposes the anti-vax lie that disease elimination being due to improved sanitation, hygiene, and diet, rather than due to vaccines.
 

The reason smallpox vaccine is no longer given to children, is the worldwide eradication of smallpox by vaccination.

Anti-vaers delayed the worldwide eradication of smallpox.

Anti-vaxers have prevented the worldwide eradication of polio.

Anti-vaxers continue to try to protect polio from eradication.

Children would no longer need polio vaccination, if it weren’t for anti-vaxers.

If you don’t like giving the polio vaccine to your child, blame the anti-vaxers.

Footnotes:

[1] Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States.
Roush SW, Murphy TV; Vaccine-Preventable Disease Table Working Group.
JAMA. 2007 Nov 14;298(18):2155-63.
PMID: 18000199

You can also read the full text of the article for free at JAMA at the link below, if you want to understand more of the details that the anti-vaxers don’t want you to understand.

Historical Comparisons of Morbidity and Mortality for Vaccine-Preventable Diseases in the United States

[2] Polio Eradication in India: The Lessons Learned.
Thacker N, Vashishtha VM, Thacker D.
Pediatrics. 2016 Oct;138(4). pii: e20160461. Epub 2016 Sep 2. Review. No abstract available.
PMID: 27590898

You can also read the full text of the article for free at Pediatrics at the link below, if you want to understand more of the details that the anti-vaxers don’t want you to understand. Pediatrics is one of the most respected pediatric medical publications in the world. Use any search engine to find what pediatric medical journals are the most respected and you will find Pediatrics near the top.

Polio Eradication in India: The Lessons Learned

.

Variation in Survival After Out-of-Hospital Cardiac Arrest Between Emergency Medical Services Agencies – Part I

 

This is a look at the data from the paper I wrote about in Are We Killing Patients With Parochialism?

What differences can we see among the EMS agencies being studied?
 


 

The best half of EMS agencies are producing twice as many good outcomes as the worse half of EMS agencies.[1]

Most of us are bad at resuscitation and those of us treating the most cardiac arrests are doing the least good.

Why do so many of us refuse to improve our standards?

What is so much more important than patient outcomes?
 

Let’s start with Figure 2 C How is survival to the emergency department distributed among EMS agencies?
 


 

ROSC to the ED (Emergency Department) looks great. The results are skewed to the right, which is what we want to see in outcomes. Unfortunately, this is not an outcome that is important. Yes, you do need to have ROSC (Return Of Spontaneous Circulation) to survive, but it is important that we not cause irreversible harm in order to get very reversible ROSC.

How reversible is ROSC?
 


 

Those distributions are similar, although they are decreased by more than half. If leaving the hospital with a pulse were the outcome that mattered, it might not be so bad.

But these are not on the same scale. The ROSC to the ED figure continues to 46%, with a greater than symbol to indicate that some will do better, while the survival to discharge figure stops at 20%, with the same greater than symbol to indicate that there are some beyond that number. How many beyond the end of the figure? The authors decided that it was not enough to waste space on, because they cut it off there.

Where would the survival to discharge percentages be on the ROSC to the ED figure?
 


 

The arrow on the right is where the 46>% bar from the ROSC to the ED figure.

It is important to put these percentages in perspective, which means looking at the differences in the numbers at the bottom.

Now we need to look at the percentage surviving with enough brain function to be able to take care of themselves – those probably not going to a nursing home. This is the group everyone wants to be in. Figure 2 B.
 


 

The percentages of patients able to care from themselves looks a lot different from the previous figures. The results are skewed to the left, which is not what we want to see. Skewed to the left means that the outcomes are mostly on the lower end of the scale – the bad end.

The percentages on the bottom of the figure have not been changed (from those used for survival to discharge), but the results have worsened (been skewed to the left).
 


 

Compared with the first image, this is a very different outcome. We should admit that ROSC to the ED and survival with the ability to take care of ourselves are very poorly correlated.

We need to stop focusing on the harmful distraction that is ROSC.

Most people consider healthy brain function to be important. There are people who insist that we give too much attention to the chemistry of brain function, as if changing a person’s brain does not change a person’s behavior. When our brain chemistry changes, we change. Similarly, when our brains are damaged, as often happens during resuscitation, the part of us that makes us the people that we are is damaged. We do not think with our hearts, nor with our guts, no matter what metaphors some of us like to use.

We are not good at resuscitating the part of the patient that matters the most to the patient.

We are not good at producing the outcome that matters the most to the patient.

We appear to be best at focusing on what matters the least.
 

If we could get the half of the EMS agencies that are not effective at producing survival with good neurological function to improve their patient care, that would result in a big increase in outcomes that matter to patients.
 

It is important that we not cause irreversible harm in order to get very reversible ROSC.
 

Also to be posted on ResearchBlogging.org when they relaunch the site.

In Part II I will look at the potentially significant differences between EMS agencies with good outcomes and EMS agencies with bad outcomes.

Footnotes:

[1] Variation in Survival After Out-of-Hospital Cardiac Arrest Between Emergency Medical Services Agencies.
Okubo M, Schmicker RH, Wallace DJ, Idris AH, Nichol G, Austin MA, Grunau B, Wittwer LK, Richmond N, Morrison LJ, Kurz MC, Cheskes S, Kudenchuk PJ, Zive DM, Aufderheide TP, Wang HE, Herren H, Vaillancourt C, Davis DP, Vilke GM, Scheuermeyer FX, Weisfeldt ML, Elmer J, Colella R, Callaway CW; Resuscitation Outcomes Consortium Investigators.
JAMA Cardiol. 2018 Sep 26. doi: 10.1001/jamacardio.2018.3037. [Epub ahead of print]
PMID: 30267053

Free Full Text from JAMA Cardiology

.

Are We Killing Patients With Parochialism?

 
The variation in approaches to resuscitation in EMS is tremendous.

Many excuses center around the need for local people to be able to claim that they know something that the evidence does not show, although they consistently fail to provide valid evidence for these claims. This local knowledge appears to be intuitive – they just know it, but cannot provide anything to support their feelings.

The latest research can be interpreted in many different ways, but it definitely does not support the claims of the advocates of parochialism.
 

Results We identified 43 656 patients with OHCA treated by 112 EMS agencies. At EMS agency level, we observed large variations in survival to hospital discharge (range, 0%-28.9%; unadjusted MOR, 1.43 [95% CI, 1.34-1.54]), return of spontaneous circulation on emergency department arrival (range, 9.0%-57.1%; unadjusted MOR, 1.53 [95% CI, 1.43-1.65]), and favorable functional outcome (range, 0%-20.4%; unadjusted MOR, 1.54 [95% CI, 1.40-1.73]).[1]

 

MOR = Median Odds Ratio – how many times more likely is something to happen.

What is most commonly measured is what matters the least – ROSC (Return Of Spontaneous Circulation). Did we get a pulse back, for even the briefest period of time, regardless of outcomes that matter.

What matters? Does the person wake up and have the ability to function as they did before the cardiac arrest.

Those who justify focusing on ROSC claim that, If we don’t get a pulse back, nothing else matters, but that is the kind of excuse used by frauds. How we get a pulse back does matter. The evidence makes that conclusion irrefutable, but there will always be those who do not accept that they are causing harm. They will make excuses for the harm they are causing. Getting ROSC helps them to feel that they are not causing harm. ROSC encourages us to give drugs like epinephrine, which have been demonstrated to not improve any survival that matters.

The means of obtaining ROSC can be compared to the means of doing anything that requires finesse. Sure, it feels good to try to force something. Sure, you can claim that forcing something is the most direct way to accomplish the goal.

Can the advocates of focusing on ROSC produce any valid evidence that their approach leads to improvements in outcomes that matter? No. The evidence contradicts their claims. The evidence has caused us to eliminate many of their treatments – treatments they claimed had to work because of physiology. As it turns out, they were wrong. They were wrong about their treatments and wrong about their understanding of physiology.

If you want to win money, bet that any new treatment will not improve outcomes that matter.
 

This variation persisted despite adjustment for patient-level and EMS agency–level factors known to be associated with outcomes (adjusted MOR for survival 1.56 [95% CI 1.44-1.73]; adjusted MOR for return of spontaneous circulation at emergency department arrival, 1.50 [95% CI, 1.41-1.62]; adjusted MOR for functionally favorable survival, 1.53 [95% CI, 1.37-1.78]).[1]

 

Is presence of a pulse upon arrival at the emergency department an important outcome? Only for billing purposes. The presence of a pulse justifies providing more, and more expensive, treatments. Is the presence of a pulse upon arrival at the emergency department a goal worth trying for? As with ROSC, only if it does not cause us to harm patients to obtain this goal, which is just something that is documented, because it is a point of transfer of patient care.
 

After restricting analysis to those who survived more than 60 minutes after hospital arrival and including hospital treatment characteristics, the variation persisted (adjusted MOR for survival, 1.49 [95% CI, 1.36-1.69]; adjusted MOR for functionally favorable survival, 1.34 [95% CI, 1.20-1.59]).[1]

 

There is a lot of variability.

What did they find?
 


 

Most of the people in EMS, who claim to be doing what is best for their patients, are making things worse.
 

69% means that there are two EMS agencies producing bad outcomes for every EMS agency producing good outcomes.

Correction – The text crossed out is not accurate. I should have thought that through a bit better before I posted it. My caption for Table 1 is accurate. However, what I should have written afterward is –

The worse half of EMS agencies are only producing half as many good outcomes as the better half of EMS agencies.

We are bad at resuscitation and those doing the most resuscitating are doing the least good.

Why do so many of us refuse to improve our standards?

What is more important than the outcomes for our patients?
 

Why are we so overwhelmingly bad at resuscitation?
 

What are the authors’ conclusions?
 

This study has implications for improvement of OHCA management. First, the analysis indicates that the highest-performing EMS agencies had more layperson interventions and more EMS personnel on scene.[1]

 

They do not conclude that we need more doctors, more nurses, or more paramedics responding to cardiac arrest.
 

Second, our findings justify further efforts to identify potentially modifiable factors that may explain this residual variation in outcomes and could be targets of public health interventions.[1]

 

We need to figure out what we are doing, because the people telling us that they know that we need intubation are lying.

We need to figure out what we are doing, because the people telling us that they know that we need epinephrine are lying.

We need to figure out what we are doing, because the people telling us that they know that we need amiodarone are lying.

We need to figure out what we are doing, because the people telling us that they know that we need ________ are lying.

How dare I call them liars?

Let them produce valid evidence that the interventions they claim are necessary actually do improve outcomes that matter.

Have them stop making excuses and start producing results.

I dare them.

The only time we have made significant improvements in outcomes have been when we emphasized chest compressions, especially bystander chest compressions, and when we emphasized bystander defibrillation.

It is time to start requiring evidence of benefit for everything we do to patients.

Our patients are too important to be subjected to witchcraft, based on opinions and an absence of research.

There is plenty of valid evidence that using only chest compressions improves outcomes.
 

Cardiocerebral resuscitation improves survival of patients with out-of-hospital cardiac arrest.
Kellum MJ, Kennedy KW, Ewy GA.
Am J Med. 2006 Apr;119(4):335-40.
PMID: 16564776 [PubMed – indexed for MEDLINE]

Cardiocerebral resuscitation improves neurologically intact survival of patients with out-of-hospital cardiac arrest.
Kellum MJ, Kennedy KW, Barney R, Keilhauer FA, Bellino M, Zuercher M, Ewy GA.
Ann Emerg Med. 2008 Sep;52(3):244-52. Epub 2008 Mar 28.
PMID: 18374452 [PubMed – indexed for MEDLINE]

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.
PMID: 18334691 [PubMed – indexed for MEDLINE]

Free Full Text at JAMA

Passive oxygen insufflation is superior to bag-valve-mask ventilation for witnessed ventricular fibrillation out-of-hospital cardiac arrest.
Bobrow BJ, Ewy GA, Clark L, Chikani V, Berg RA, Sanders AB, Vadeboncoeur TF, Hilwig RW, Kern KB.
Ann Emerg Med. 2009 Nov;54(5):656-662.e1. Epub 2009 Aug 6.
PMID: 19660833 [PubMed – indexed for MEDLINE]

And more.

 

It is not ethical to insist on giving treatments to patients in the absence of valid evidence of benefit to the patient. We need to begin to improve our ethics.
 

Also to be posted on ResearchBlogging.org when they relaunch the site.

Footnotes:

[1] Variation in Survival After Out-of-Hospital Cardiac Arrest Between Emergency Medical Services Agencies.
Okubo M, Schmicker RH, Wallace DJ, Idris AH, Nichol G, Austin MA, Grunau B, Wittwer LK, Richmond N, Morrison LJ, Kurz MC, Cheskes S, Kudenchuk PJ, Zive DM, Aufderheide TP, Wang HE, Herren H, Vaillancourt C, Davis DP, Vilke GM, Scheuermeyer FX, Weisfeldt ML, Elmer J, Colella R, Callaway CW; Resuscitation Outcomes Consortium Investigators.
JAMA Cardiol. 2018 Sep 26. doi: 10.1001/jamacardio.2018.3037. [Epub ahead of print]
PMID: 30267053

Free Full Text from JAMA Cardiology

.

Why are we still intubating, when there is no evidence of benefit and we refuse to practice this “skill”?

 
Also to be posted on ResearchBlogging.org when they relaunch the site.

The results are in from two studies comparing intubation with laryngeal airways. There continues to be no good reason to intubate cardiac arrest patients. There is no apparent benefit and the focus on this rarely used, and almost never practiced, procedure seems to be more for the feelings of the people providing treatment, than for the patients.
 

Patients with a short duration of cardiac arrest and who receive bystander resuscitation, defibrillation, or both, are considerably more likely to survive and are also less likely to require advanced airway management.22 This problem of confounding by indication is an important limitation of many large observational studies that show an association between advanced airway management and poor outcome in out-of-hospital cardiac arrest.23 This study found that 21.1% (360/1704) of patients who did not receive advanced airway management achieved a good outcome compared with 3.3% (251/7576) of patients who received advanced airway management.[1]

 

In other words, we are the least skilled, are the least experienced, and we have the least amount of practice, but we are attempting to perform a difficult airway skill under the least favorable conditions. Ironically, we claim to be doing what is best for the patient. We are corrupt, incompetent, or both.

We also do not have good evidence that any kind of active ventilation is indicated for cardiac arrest, unless the cardiac arrest is due to respiratory conditions. Passive ventilation, which is the result of high quality chest compressions, appears to produce better outcomes (several studies are listed at the end).

We need to stop considering our harmful interventions to be the standard and withholding harmful treatments to be the intervention. We are using interventions that have well known and serious adverse effects. This attempt to defend the status quo, at the expense of honesty, has not been beneficial to patients.
 

The ETI success rate of 51% observed in this trial is lower than the 90% success rate reported in a meta-analysis.29 The reasons for this discordance are unclear. Prior reports of higher success rates may be susceptible to publication bias.[2]

 

Is that intubation success rate lower than you claim for your organization? Prove it.
 

Another possibility is that some medical directors encourage early rescue SGA use to avoid multiple unsuccessful intubation attempts and to minimize chest compression interruptions.5 Few of the study EMS agencies had protocols limiting the number of allowed intubation attempts, so the ETI success rate was not the result of practice constraints.[2]

 

Is there any reason to interrupt chest compressions, which do improve outcomes that matter, to make it easier to intubate, which does not improve any outcomes that matter? No.
 

While the ETI proficiency of study clinicians might be questioned, the trial included a diverse range of EMS agencies and likely reflects current practice.[2]

 

This is the state of the art of intubation in the real world of American EMS. Making excuses shows that we are corrupt, incompetent, or both.
 


I no longer have the link, but I think that this image came from Rescue Digest a decade ago.
 

These results contrast with prior studies of OHCA airway management. Observational studies have reported higher survival with ETI than SGA, but they were nonrandomized, included a range of SGA types, and did not adjust for the timing of the airway intervention.9,10,31-34 [2]

 

We should start doing what is best for our patients.

We should not continue to defend resuscitation theater – putting on a harmful show to make ourselves feel good.

What would a competent anesthesiologist use in the prehospital setting? Something that offers a benefit to the patient.

There is also an editorial analyzing these two studies.[3]

It is time to start requiring evidence of benefit for everything we do to patients.

Our patients are too important to be subjected to witchcraft, based on opinions and an absence of research.

There is plenty of valid evidence that using only chest compressions improves outcomes.
 

Cardiocerebral resuscitation improves survival of patients with out-of-hospital cardiac arrest.
Kellum MJ, Kennedy KW, Ewy GA.
Am J Med. 2006 Apr;119(4):335-40.
PMID: 16564776 [PubMed – indexed for MEDLINE]

Cardiocerebral resuscitation improves neurologically intact survival of patients with out-of-hospital cardiac arrest.
Kellum MJ, Kennedy KW, Barney R, Keilhauer FA, Bellino M, Zuercher M, Ewy GA.
Ann Emerg Med. 2008 Sep;52(3):244-52. Epub 2008 Mar 28.
PMID: 18374452 [PubMed – indexed for MEDLINE]

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.
PMID: 18334691 [PubMed – indexed for MEDLINE]

Free Full Text at JAMA

Passive oxygen insufflation is superior to bag-valve-mask ventilation for witnessed ventricular fibrillation out-of-hospital cardiac arrest.
Bobrow BJ, Ewy GA, Clark L, Chikani V, Berg RA, Sanders AB, Vadeboncoeur TF, Hilwig RW, Kern KB.
Ann Emerg Med. 2009 Nov;54(5):656-662.e1. Epub 2009 Aug 6.
PMID: 19660833 [PubMed – indexed for MEDLINE]

And more.

 

It is not ethical to insist on giving treatments to patients in the absence of valid evidence of benefit to the patient. We need to begin to improve our ethics.

Also read/listen to these articles/podcasts released after I published this (I do not know the date of the Resus Room podcast) –

The Great Prehospital Airway Debate
August 31, 2018
Emergency Medicine Literature of Note
by Ryan Radecki
Article
 

EM Nerd-The Case of the Needless Imperative
August 31, 2018
EMNerd (EMCrit)
by Rory Spiegel
Article
 

Intubation or supraglottic airway in cardiac arrest; AIRWAYS-2
The Resus Room
Podcast with Simon Laing, Rob Fenwick, and James Yates with guest Professor Jonathan Benger, lead author of AIRWAYS-2.
Podcast, images, and notes
 

Footnotes:

[1] Effect of a Strategy of a Supraglottic Airway Device vs Tracheal Intubation During Out-of-Hospital Cardiac Arrest on Functional Outcome: The AIRWAYS-2 Randomized Clinical Trial
Jonathan R. Benger, MD1; Kim Kirby, MRes1,2; Sarah Black, DClinRes2; et al Stephen J. Brett, MD3; Madeleine Clout, BSc4; Michelle J. Lazaroo, MSc4; Jerry P. Nolan, MBChB5,6; Barnaby C. Reeves, DPhil4; Maria Robinson, MOst2; Lauren J. Scott, MSc4,7; Helena Smartt, PhD4; Adrian South, BSc (Hons)2; Elizabeth A. Stokes, DPhil8; Jodi Taylor, PhD4,5; Matthew Thomas, MBChB9; Sarah Voss, PhD1; Sarah Wordsworth, PhD8; Chris A. Rogers, PhD4
August 28, 2018
JAMA. 2018;320(8):779-791.
doi:10.1001/jama.2018.11597

Abstract from JAMA.

[2] Effect of a Strategy of Initial Laryngeal Tube Insertion vs Endotracheal Intubation on 72-Hour Survival in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial
Henry E. Wang, MD, MS1,2; Robert H. Schmicker, MS3; Mohamud R. Daya, MD, MS4; et al Shannon W. Stephens, EMT-P2; Ahamed H. Idris, MD5; Jestin N. Carlson, MD, MS6,7; M. Riccardo Colella, DO, MPH8; Heather Herren, MPH, RN3; Matthew Hansen, MD, MCR4; Neal J. Richmond, MD9,10; Juan Carlos J. Puyana, BA7; Tom P. Aufderheide, MD, MS8; Randal E. Gray, MEd, NREMT-P2; Pamela C. Gray, NREMT-P2; Mike Verkest, AAS, EMT-P11; Pamela C. Owens5; Ashley M. Brienza, BS7; Kenneth J. Sternig, MS-EHS, BSN, NRP12; Susanne J. May, PhD3; George R. Sopko, MD, MPH13; Myron L. Weisfeldt, MD14; Graham Nichol, MD, MPH15
August 28, 2018
JAMA. 2018;320(8):769-778.
doi:10.1001/jama.2018.7044

Free Full Text from JAMA.

[3] Pragmatic Airway Management in Out-of-Hospital Cardiac Arrest
Lars W. Andersen, MD, MPH, PhD1; Asger Granfeldt, MD, PhD, DMSc2
August 28, 2018
JAMA. 2018;320(8):761-763. doi:10.1001/jama.2018.10824

Abstract from JAMA.

.

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

 
Also to be posted on ResearchBlogging.org when they relaunch the site.

Do we have to stop using epinephrine (adrenaline in Commonwealth countries) for cardiac arrest?
 


 

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”.[1]

The results showed that 1 mg of epinephrine every 3 – 5 minutes is even worse than I expected, but a lot of the more literate doctors have not been using epinephrine that way. What does this research tell us about their various methods? The podcast REBEL Cast (Rational Evidence Based Evaluation of Literature in Emergency Medicine) has a discussion of this question in REBEL Cast Ep56 – PARAMEDIC-2: Time to Abandon Epinephrine in OHCA?.[2]

The current ACLS/ILCOR (Advanced Cardiac Life Support/International Liaison Committee on Resuscitation) advice on epinephrine does not state that epinephrine is a good idea, or even require that you give epinephrine to follow their protocol –
 

The major changes in the 2015 ACLS guidelines include recommendations about prognostication during CPR based on exhaled CO2 measurements, timing of epinephrine administration stratified by shockable or nonshockable rhythms, and the possibility of bundling treatment of steroids, vasopressin, and epinephrine for treatment of in-hospital arrests. In addition, the administration of vasopressin as the sole vasoactive drug during CPR has been removed from the algorithm.[3]

 

What was the ACLS/ILCOR advice in the 2010 guidelines?
 

The 2010 Guidelines stated that it is reasonable to consider administering a 1-mg dose of IV/IO epinephrine every 3 to 5 minutes during adult cardiac arrest.[4]

 

This is in a paragraph that links to the PICO (Population-Intervention-Comparator-Outcomes) question that has been an open question for over half a century – In cardiac arrest, is giving epinephrine better than not giving epinephrine?[5]

They only considered it reasonable, based on low quality evidence.

What was the ACLS/ILCOR advice in the 2015 guidelines?
 

Standard-dose epinephrine (1 mg every 3 to 5 minutes) may be reasonable for patients in cardiac arrest (Class IIb, LOE B-R).[6]

 

Again, ACLS/ILCOR only considered a dose of epinephrine to be reasonable. Again, this was based on low quality evidence. I am not criticizing the efforts of those who worked on the Jacobs study of adrenaline vs. placebo, because they were stopped by the willfully ignorant opponents of science.[7]

What about the method of attempting to titrate an infusion to the hemodynamic response, which Dr. Swaminathan and Dr. Rezaie alluded to?

There is a lot of anecdotal enthusiasm from doctors who use this method, but I do not know of any research that has been published comparing outcomes using this method with anything else. How do we know that the positive reports from doctors are anything other than confirmation bias? We don’t.

This year is the 200th anniversary of the publication of the very first horror novel – Frankenstein; or, The Modern Prometheus. The doctor in the novel used electricity to raise the dead (and the subjects were very dead). There were no chest compressions in the novel, but it is interesting that we have barely made progress from the fiction imagined by an 18 year old with no medical training, although she did have the opportunity to listen to many of the smartest people in England discuss science. Mary Godwin (later Mary Wollstonecraft Shelley by marriage) was 16 when she started writing the novel.[8]

We have barely made more progress at resuscitation than a teenager did 200 years ago in a novel. Most of our progress has been in finally admitting that the treatments we have been using have been producing more harm than benefit. Many of us are not even that honest about the harm we continue to cause.

We dramatically improved resuscitation in one giant leap – when we focused on high quality chest compressions and ignoring the medical theater of advanced life support.

There are two treatments that work during cardiac arrest – high quality chest compressions and rapid defibrillation.

Why haven’t we made more progress?

We have been too busty making excuses for remaining ignorant.

We need to stop being so proud of our ignorance.

We now know that amiodarone doesn’t work for cardiac arrest (and is more dangerous than beneficial for ventricular tachycardia – even adenosine appears to be better for VTach), atropine doesn’t work for cardiac arrest, calcium chloride doesn’t work for cardiac arrest (unless it is due to hyperkalemia/rhabdomyolysis), vasopressin doesn’t work for cardiac arrest, high dose epinephrine doesn’t work for cardiac arrest, standard dose epinephrine doesn’t work for cardiac arrest – in other words, we have tried all sorts of drugs, based on hunches and the weakest of evidence, but we still haven’t learned that there isn’t a magic resuscitation drug.

Should anyone be using any epinephrine to treat cardiac arrest outside of a well controlled study?

No.

Also –

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

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

[2] REBEL Cast Ep56 – PARAMEDIC-2: Time to Abandon Epinephrine in OHCA?
Anand Swaminathan, MD and Salim Rezaie, MD, FACEP
July 20, 2018
Episode 56 and show notes

[3] Introduction
Part 7: Adult Advanced Cardiovascular Life Support
2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Mark S. Link, Lauren C. Berkow, Peter J. Kudenchuk, Henry R. Halperin, Erik P. Hess, Vivek K. Moitra, Robert W. Neumar, Brian J. O’Neil, James H. Paxton, Scott M. Silvers, Roger D. White, Demetris Yannopoulos, Michael W. Donnino
Circulation. 2015;132:S444-S464, originally published October 14, 2015
https://doi.org/10.1161/CIR.0000000000000261
Introduction – scroll down to the last paragraph

[4] Vasopressors in Cardiac Arrest: Standard-Dose Epinephrine
Part 7: Adult Advanced Cardiovascular Life Support
2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Mark S. Link, Lauren C. Berkow, Peter J. Kudenchuk, Henry R. Halperin, Erik P. Hess, Vivek K. Moitra, Robert W. Neumar, Brian J. O’Neil, James H. Paxton, Scott M. Silvers, Roger D. White, Demetris Yannopoulos, Michael W. Donnino
Circulation. 2015;132:S444-S464, originally published October 14, 2015
https://doi.org/10.1161/CIR.0000000000000261
2010 epinephrine advice

[5] Epinephrine Versus Placebo
ILCOR Scientific Evidence Evaluation and Review
Epinephrine Versus Placebo

 

Among adults who are in cardiac arrest in any setting (P), does does the use of epinephrine (I), compared with compared with placebo or not using epinephrine (C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year, ROSC (O)?

 

[6] 2015 Recommendation—Updated
Part 7: Adult Advanced Cardiovascular Life Support
2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Mark S. Link, Lauren C. Berkow, Peter J. Kudenchuk, Henry R. Halperin, Erik P. Hess, Vivek K. Moitra, Robert W. Neumar, Brian J. O’Neil, James H. Paxton, Scott M. Silvers, Roger D. White, Demetris Yannopoulos, Michael W. Donnino
Circulation. 2015;132:S444-S464, originally published October 14, 2015
https://doi.org/10.1161/CIR.0000000000000261
2015 Recommendation—Updated

[7] 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.

 

[8] Frankenstein
Wikipedia
Article

Edited 12-27-2018 to correct link to pdf of Jacobs study in footnote 7.

.