Furosemide is good for filling the patient’s bladder, but the patient probably did not call for help filling his/her bladder.

- Rogue Medic

$16M on EMS Stroke Trial? Dr. Rick Bukata Wants His Money Back!


 

FAST-MAG[1] actually has good methodology, so why is Dr. Rick Bukata so upset? Is this just USC vs. UCLA off the field/court?

Should the hypothesis being tested have received the Queen for a Decade treatment?

He wants his money back? Roughly 160 million tax payers in the US, so $0.10 per tax payer, but he makes more than the average schlub, so maybe as much as 50 cents for him. He can’t even buy enough caffeine to raise his blood pressure with that.
 

In a commentary regarding the IMAGES trial by Larry Goldstein of the Duke Center for Cerebrovascular Disease in the same issue of the Lancet in which the study was published, he noted that of more than 40 clinical trials of “neuroprotectants” involving over 11,000 patients, none has shown any evidence of benefit. Ten years later, the same is true.[2]

 

But look at the animal studies!

But look at the time being saved!

The authors actually like to repeat the term Golden Hour – as if that is new or valid.
 

So, if you are still a believer in the potential of magnesium, why not try and give magnesium in a pilot clinical study involving stroke patients in the ED? It would have been a relatively simple study to do. It could have been performed in selected EDs throughout the country and the answer would have been established in a fraction of eight years and at a very small fraction of $16 million.

Instead, the Fast-Mag investigators decide that giving magnesium in the field (probably about 10-20 minutes faster than could be given in the ED) would be a reasonable study.[2]

 

Gosh, when he brings reason into the argument, it just seems that the other side has none.

What could the money have been spent on?

Epinephrine vs. placebo in cardiac arrest? The number of lives affected is large and we are currently treating based on philosophy, not science.

IV (IntraVenous) bolus NTG (NiTroGlycerin – GTN GlycerylTriNitrate in Commonwealth countries) vs. SL (SubLingual) NTG for acute CHF (Congestive Heart Failure)? This affects even more patients than cardiac arrest and there is good evidence that IV bolus NTG dramatically improves outcomes, while SL NTG is not based on evidence.

Excited delirium treatment with various IM (IntraMuscular) medications to see what is safest and most effective and at what dose. A large trial would be necessary.

With no good reason to be optimistic about outcomes, why take this multimillion dollar long shot?

Maybe it has to do with tPA (tissue Plasminogen Activator) and the failure to get emergency physicians to accept the poor research on tPA – tPA showed harm, or no benefit, in 9 out of 11 studies.[3]

Ironically, if those studies used methodology similar to this study, that could be showed harm, or no benefit, in 11 out of 11 studies.

Dr. Jeffrey L. Saver, one of the authors, has a presentation on FAST-MAG that spends a lot of time on tPA, even prehospital tPA.

What does Dr. Sarver consider to be positive about FAST-MAG? Here are some of his slides.[4]
 


 

FAST-MAG means more tPA use.
 


 

FAST-MAG means doing a lot of things that have not been done before and expecting the outcome to be good.

This is the kind of person who starts turning all of the dials on a ventilator and then looks at the patient to see what the result is.

A reasonable approach to research is to limit variables, not brag about how much prudence has been abandoned.
 


 

FAST-MAG means time will be saved, but . . . .
 

Walter Koroshetz, MD, neurologist and deputy director of the National Institutes of Health’s (NIH’s) National Institute of Neurological Disorders and Stroke, sponsor of the FAST-MAG study, says that lessons can be learned from the trial.[5]

 

“The NIH have a new network to do more prehospital trials, but we need phase 2 studies first that demonstrate some biological effect before going into a large costly phase 3 trials.”[5]

 

This is a $16 million bet that time is the only factor that matters.

I hope these doctors do not drive the way they gamble.

What were the results?

The results were the same as all of the previous studies of magnesium – no improvement.

There is no Magnesium Golden Hour.
 

And, please, no – don’t even consider the idea of giving tPA in the field.[2]

 

Well, . . . .
 

Dr. Saver explained that tPA cannot be given at present in a prehospital setting because hemorrhagic stroke has to be ruled out with computed tomography (CT). The use of ambulances with a CT scanner on board has been studied in Germany and is now starting to be tested in the United States.[5]

 

Be very afraid.

On the other hand, the authors did not rush this treatment into EMS protocols, as we recently have in EMS in so many places with therapeutic hypothermia, based entirely on research done in the ED (Emergency Department). It works in the ED, but not in the ambulance. :oops:

FAST-MAG was approved in 1999, several years after the EMS nifedipine (Procardia) for hypertensive crisis crisis. There was no study in the EMS setting of a treatment for the EMS setting. This involved treatment of the surrogate endpoint of blood pressure numbers, which makes for an easy win, such as a systolic drop of 250 -> 90 in ten minutes. :oops:

We need a balance between rushing to add the new cool treatment (and the predictable removal of the treatment decades later) and the inappropriate rush to a large scale trial of something that has repeatedly failed smaller studies.
 

Go read Dr. Bukata’s full article.

-

Footnotes:

-

[1] Methodology of the Field Administration of Stroke Therapy – Magnesium (FAST-MAG) phase 3 trial: Part 2 – prehospital study methods.
Saver JL, Starkman S, Eckstein M, Stratton S, Pratt F, Hamilton S, Conwit R, Liebeskind DS, Sung G, Sanossian N; FAST-MAG Investigators and Coordinators.
Int J Stroke. 2014 Feb;9(2):220-5. doi: 10.1111/ijs.12242.
PMID: 24444117 [PubMed - in process]

Methodology of the Field Administration of Stroke Therapy – Magnesium (FAST-MAG) phase 3 trial: Part 1 – rationale and general methods.
Saver JL, Starkman S, Eckstein M, Stratton S, Pratt F, Hamilton S, Conwit R, Liebeskind DS, Sung G, Sanossian N; FAST-MAG Investigators and Coordinators.
Int J Stroke. 2014 Feb;9(2):215-9. doi: 10.1111/ijs.12243. Epub 2014 Jan 13.
PMID: 24444116 [PubMed - in process]

-

[2] $16M on EMS Stroke Trial? I Want My Money Back!
by Rick Bukata, MD
March 24, 2014
Emergency Physicians monthly
Article

-

[3] The Guideline, The Science, and The Gap
Wednesday, April 17, 2013
Dr. David Newman
Smart EM
Article

-

[4] Treat Stroke in the Field:
Lessons from the NIH FAST-MAG Trial

Jeffrey L. Saver, MD, Professor of Neurology
UCLA Stroke Center
2012
Presentation Slides in PDF Downoad format.

-

[5] FAST-MAG: No Benefit of Prehospital Magnesium in Stroke
Sue Hughes
February 14, 2014
Medscape
Article

.

Top Ten Resuscitation Headlines from Rescue Digest – Read ‘Em and Learn

 

This should catch your attention -
 

RescueDigest’s Top Picks of essential resources for critical topics in emergency services.
 

What should we be paying attention to?
 

Headline #1: EMS Saves Everyone / EMS Saves No One[1]

 

If you read the main stream media, you get one version, or the other, or even both in the same week/month/year.

Why?

If we get our science reporting from the news media, we are not getting valid science reporting.

We are probably getting a poor translation of a secondhand account of what the researcher denied was the result of the study.

Trust the media. We would never misrepresent anything!
 


Image credit.
 

This article provides evidence to explain what the truth is.
 

Does EMS save everyone?

We haven’t put the funeral homes out of business, yet – and we never will.

Does EMS save no one?

Systems that focus on excellent uninterrupted compressions and rapid defibrillation save 40% – 60% of the patients who are in a shockable rhythm when EMS arrives.

You were dead.

No pulse.

No brain function.

Dead.

Dead.

Dead.
 

But – after EMS treatment – you are alive.

This is a true improved outcome, not getting a pulse back only to die in the ICU, or to die in a few weeks/months in a nursing home without ever waking up.

Your brain is working again.

You can play with your children/grandchildren, again.

You are alive.

Only 40% to 60% of patients in shockable rhythms when EMS arrives!

Not perfect, but nothing is perfect. Less than perfect is imperfect, but everything is imperfect. Less than perfect, but better than nothing is still better than nothing. 40% to 60% are better than they would be with nothing.

The NNT (Number Needed to Treat) is a little more than two.

That makes this one of the most effective medical treatments available. Prevention of cardiac arrest is still better, but when prevention does not work, this frequently does.

Less than perfect is the best that is available from real medicine. Charlatans will promise to do better, but they will end up making excuses for failure – and they cannot resuscitate.
 

The basic trouble, you see, is that people think that “right” and “wrong” are absolute; that everything that isn’t perfectly and completely right is totally and equally wrong.[2]

 

What about the rest of the headlines?

Don’t end up like this –
 


Image credit.
 

Go read what Rommie Duckworth is writing.

Go through the slides from his presentation. If you get a chance, go to a conference where he is presenting, such as EMS Today in Washington, D.C., a little over a week from today.
 

Education
2:15PM- 3:15PM
Don’t Lose Your Cool: Dealing With Problem Students

Room: 207B
The Know-it-all. The Worrier. The Heckler. The Rambler. The Cheater. Is one rotten apple going to spoil your whole program? This program provides educators of all levels with insight into the sources of student issues as well as the mistakes that instructors commonly make that contribute to classroom unrest. Using read more…

Speaker
Rommie Duckworth
Director
N.E. Ctr. for Rescue & Emerg. Med.
Sherman, CT, United States
[3]

 

-

Footnotes:

-

[1] RescueDigest Resources: Top Ten Resuscitation Headlines
Rescue Digest
Posted on Jan 29, 2014
Rom Duckworth
Article

-

[2] The Relativity of Wrong
The Skeptical Inquirer
Fall 1989, Vol. 14, No. 1, Pp. 35-44
By Isaac Asimov
Article

Read the whole article. It is not long, but it is an excellent introduction to how science works.

-

[3] EMS Today
February 5-8, 2014
Walter E. Washington Convention Center
Washington D.C.
Information

Results of search for Rommie Duckworth in EMS Today’s schedule search.

.

1-Union-801 Podcast Discussing Epi for V Tach, Cardioversion, Procainamide, Paralytics During Hypothermia, Quality of CPR, and DNA Transfer


 

 
On 1-Union-801 John Broyles and I discussed some things that I had written. I was supposed to be on the podcast two weeks earlier, but I am on duty at the time of the podcast, and I had a call a few minutes before the show. This podcast was not interrupted by any calls.[1]
 

Go listen to the podcast.
 

Epinephrine for V Tach – Instant Death or Effective Treatment?

What might happen if epinephrine is given for this V Tach (Ventricular Tachycardia)?
 

Click on images to make them larger. Image credit and article about epinephrine for V Tach.[2]
 

We also discuss sychronized cardioversion and procainamide.
 
Other things we discussed (in order) were –

Do Paralytics Improve Outcomes Following Resuscitation?

We want to minimize movement after starting therapeutic hypothermia. Is the use of paralytics the right way to do this?
 

Un-extraordinary measures: Stats show CPR often falls flat

The author appears to take the comments of Dr. David Newman completely out of context in order to make a point that I do not think Dr. Newman would ever make.

Who is Dr. Newman?
 

 

SMART EM

Dr. David Newman, and sometimes Dr. Ashley Shreves, write and podcast about research and emergency medicine. There is an excellent deconstruction of the ACLS (Advanced Cardiac Life Support) guidelines and the lack of evidence for the drugs recommended in the guidelines.

The NNT is another excellent site that is here, too.

At Annals of Emergency Medicine, Dr. Newman and Dr. Ashley Shreves present excellent summaries of the articles in each issue. Annals of Emergency Medicine Podcast

I also mentioned Dr. Richard Levitan’s No Desat approach of using high flow oxygen by nasal cannula, which works wonders. Read about No Desat!
 

Apparent DNA Transfer by Paramedics Leads to Wrongful Imprisonment

Do we use gloves properly?

Is DNA transfer between patients an indication of a lack of use of gloves?
 

Go listen to the podcast.
 

-

Footnotes:

-

[1] Rogue Medic Saved Our Bacon 20 Jul 13
1-Union-801
John Broyles
Podcast page.

-

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

Free Full Text from PubMed Central.

.

Comment on Are We Killing People With ROSC?

 

In the comments to Are We Killing People With ROSC? Adam Thompson, EMT-P of Paramedicine 101 writes –
 

Go figure, right? I suppose that’s where the old H’s & T’s come in…

 

The Hs and Ts do not really affect the dose of epinephrine.

I have never liked the Hs and Ts mnemonic. I know what you’re thinking: ‘Did he recall six Hs, or only five?’ Well, to tell you the truth, in all this excitement I kind of lost track myself. But, being as this is epinephrine, the most powerful cardiotoxin in the world, and would blow your head clean off, you’ve got to ask yourself one question: ‘Do I feel lucky?’ Well, do ya, PUNK?

Since PUNK is the patient, PUNK is not likely to respond. PUNK is dead.

There are arguments that other drugs are more powerful cardiotoxins, but they are not routinely used for resuscitation.

 

I have always thought it was crazy that if someone has a ‘heart attack’ we fill their static vasculature with epinephrine, so when they get a pulse back, they now have a chemical pumping through their blood that is known to be lethal in people with acute coronary syndrome.

 

The blood should not be static if there are effective chest compressions. Nobody should be considering any drugs in the absence of chest compressions for a cardiac arrest patient.
 

Also, if it constricts the blood vessels of the entire body, wouldn’t that include the cerebral arteries…making cerebral anoxia worse…? “But hey, if we get pulses back, who cares?”, says the cretin medic.

 

Epinephrine has both alpha and beta effects, so there is probably a combination of constriction and dilation of the arteries.

It does not appear that epinephrine produces the beneficial effects that the physiologists claim that epinephrine produces, based on their knowledge of physiology. At least, no beneficial effects other than the supposed beneficial effect of ROSC (Return Of Spontaneous Circulation), which seems to be harmful for those who receive epinephrine. For physiologists, maybe understanding of the word beneficial is inconceivable.

Any physiologic claim that cannot be backed up by improved outcomes is just an example of the arrogance of ignorance.

Half a century of hundreds of thousands of patients treated each year, but still no evidence of benefit.

What? Increased ROSC is a benefit?

It allows the family to say good-bye to their comatose family member for a price that is profligate.

It allows the EMS crew to claim they had a save!

It allows us to pretend that a pulse and a life are the same thing.
 


Image credit.
 

If we do not understand the difference between ROSC and a living, thinking person, then ROSC is a reasonable goal.
 

ROSC is not a reasonable goal.

.

Are We Killing People With ROSC?


 

Why do we keep paying attention to studies that only look at ROSC (Return Of Spontaneous Circulation)?

It is true that ROSC is associated with survival to discharge, but as we use treatments to increase ROSC, we only seem to increase the rate of death in the hospital.

We do not increase the rate of survival.
 

Epinephrine (Adrenaline) produces a lot more ROSC, but appears to produce worse survival.

What is it about epinephrine that causes so many more people to die before they wake up from a coma?

Why do we keep trying to put people in short-term comas, before admitting that they are dead?

Why are we still using a treatment that only causes a brief pulse, when what we want is a treatment that increases the rate of survival to discharge with a working brain?
 

Even ventilations seem to dramatically decrease survival.
 


Click on images to make them larger.
 

Patients had dramatically better survival without ventilations.[1]
 

Don’t change the subject. What about the epi?
 

This is comparing three different treatments HDE (High-Dose Epinephrine), SDE (Standard-Dose Epinephrine), and NE (NorEpinephrine). The lines for the HDE and NE are so close to each other, that you may not be able to see the gold line.[2]
 

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


 

More ROSC, but fewer survivors.

Shouldn’t the standard of care improve outcomes?
 

 

Even the patients who only received the minimum dose – 1 mg – had worse outcomes.[4]

It is possible that there is a subgroup that does benefit from epinephrine – perhaps patients who have ROSC, but remain very bradycardic and lose pulses again. However, there appears to be no attempt to identify any patients who actually may benefit.

This binary, all or nothing, approach is dangerous and nothing new. Five centuries ago Paracelsus gave important advice that we continue to ignore.
 

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

Dr. David Newman at The NNT reviewed ACLS medications and concluded that there is no evidence of benefit.[5]
 


 

The patients who receive epinephrine are those who remain dead long enough to be treated with epinephrine.

Why do we assume that their outcomes would be any worse without epinephrine?

This is the arrogance of ignorance. We don’t know and we don’t want to know.

-

Footnotes:

-

[1] 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.
PMID: 20370759 [PubMed - indexed for MEDLINE]

Free Full Text from Academic Emergency Medicine.

-

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

-

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

Free Full Text from JAMA.

-

[4] Wide variability in drug use in out-of-hospital cardiac arrest: A report from the resuscitation outcomes consortium.
Glover BM, Brown SP, Morrison L, Davis D, Kudenchuk PJ, Van Ottingham L, Vaillancourt C, Cheskes S, Atkins DL, Dorian P; the Resuscitation Outcomes Consortium Investigators.
Resuscitation. 2012 Jul 31. [Epub ahead of print]
PMID: 22858552 [PubMed - as supplied by publisher]

-

[5] NIPPV for CHF Works, ACLS Algorithms Do Not
by David Newman, MD
September 26, 2012
Emergency Physicians Monthly
Article

.

Do we know that these treatments do not help?

 

In response to The Parachute Study as an Objection to Studying Ventilations in Cardiac Arrest, Can’t say, clowns will eat me writes –
 

But my why not is based upon things that we know do work vs things(drugs/IVs/advanced airways) that we know don’t help.

 

Actually, we do not know if epinephrine is harmful. The lack of evidence of benefit is also a lack of unambiguous evidence of harm.

We just don’t know.

We are practicing alternative medicine.

We are too dumb and/or too arrogant to realize how little we know.

There probably are some patients who do benefit from epinephrine, but I suspect that it would be at lower doses, perhaps much lower doses, and combined with medications to decrease the brain damage that seems to be caused by epinephrine. Nitroprusside, nitroglycerin, adenosine, and others have been used with some success.

Again, we do not know.

We have been too reckless with our patients’ lives to bother to find out. It is all just a big bet with not enough information for anyone to know what is right. And that’s not good.
 


Image credit.
 

So is that really unethical if you get the em PHA sis on the right SYL lable?

 

We have no idea what emphasis is right, or what syllable is right, because we refuse to turn the light on and look at what we are doing.

We are not ethical.

Ethics would require a respect for our patients.

Finding out if a treatment actually works would be something we would insist on – if we actually had any respect for our patients.

If we were ethical, we would tell our patients the truth.

Something like this –
 

We do not know if this treatment leads to improved outcomes, worse outcomes, if there is any benefit, or if there are equal amounts of harm and benefit.

It is reasonable to assume that all treatments cause some harm, but without any good evidence, there is no way we can honestly tell you if this treatment is likely to cause you more harm than benefit.

Some day someone will be able to find out, but that will probably still be years away.

You just are not important enough to get a treatment that works.

 

For how many EMS treatments is this the truth?

Cardiac arrest treatments except compressions and defibrillation, spinal immobilization, . . . .

.

Does the Goal of a Pulse Lead to Bad Resuscitation Decisions

ResearchBlogging.org
 

First, this is a paper that was just added to the Articles In Press for Resuscitation with the editing not yet completed. Do not fault the authors for the lack of polish. The paper does address some interesting aspects of resuscitation.

ROSC (Return Of Spontaneous Circulation) is the goal for many people.

ROSC is a red herring.

Those of us who think ROSC is important do not seem to understand how much long-term damage we can do in our attempts to get ROSC, or to get ROSC quickly.

This study helps to point out some of the inconsistencies with our ROSC fetish.

Here is a table of the results from the study comparing early epinephrine (≤10 minutes) with late epinephrine (>10 minutes).
 


Click on images to make them larger.
 

Everything highlighted in blue is favoring early epinephrine and statistically significant.

Overall, things look good for early epinephrine, but VF/VT (Ventricular Fibrillation/Ventricular Tachycardia) is most responsive to resuscitation, yet the results for VF/VT never reach statistical significance. VF/VT may also be most associated with an early response

There is only a trend toward better ROSC for VF/VT, but as with the NINDS study of tPA for ischemic stroke, the healthiest patients are in the intervention group, so they are expected to have better outcomes.
 
With asystole there are survivors with late epinephrine, but no survivors with early epinephrine. What should we make of that? It is far from statistically significant, but there is not even a trend toward more ROSC with early epinephrine.
 

PEA (Pulseless Electrical Activity) has not just a trend toward more ROSC with early epinephrine, the results are statistically significant.

One of the reasons may be that PEA is sometimes due to assessment problems. We used to call it EMD (Electro-Mechanical Dissociation) because many of us assumed that if no pulse could be palpated, there was no cardiac output. These were termed pseudo-EMD, since imaging could show that there is heart motion, even though there is no palpable pulse.

I have had a handful of patients who were awake and alert, but did not have any palpable pulses. Clearly, EMD is not a description of reality.

How many of these patients are responding to being shaken up, rather than to the mechanical effects of chest compressions in the circulation? We do not know.
 

Early Epi may increase blood pressure to allow palpation of a pulse in cases with presumed PEA, but who are actually cases of “pseudo-PEA” which have some cardiac output but not enough to be identified clinically.[1]

 
 

Modified portion of EMS 12 Lead image.
 

Then there are the expected confounders in this kind of study. Faster response times would be expected to result in earlier epinephrine and less deterioration of the rhythm to asystole.
 


 

The faster response times occur in fewer patients, so there should be a much wider confidence interval/standard deviation. That is not the case, because there is an upper limit on the numbers that can be included. The numbers include response time, time to patient contact, time to establish access, and time to epinephrine. All of those have to be less that 11 minutes combined.

Bystander CPR is much more common with early epinephrine. This may be related the higher incidence of arrest in public, but the bystander CPR rate is about twice as high as the rate of arrest in public.
 


 

With early epinephrine we have a decrease from the odds of ROSC to the odds of survival.

With witnessed arrest, bystander CPR, and VF/VT the opposite is true.

With VF/VT the difference is dramatic.

Is this an indication of the effect of epinephrine on survival that we have seen in other studies?
 


 

 

Clearly more work is needed to understand the importance of the timing of epi administration and its impact on outcomes from OHCA.[1]

 
OHCA is Out of Hospital Cardiac Arrest.

Clearly more work is needed to understand the importance of the timing effects of epi administration and its impact on outcomes from OHCA.

Why should we assume that it is the timing and not the drug?

Maybe the problem is using such a drug that is so dangerous to the heart to treat heart problems.

Samuel Hahnemann would love this use of epinephrine, just at a much lower dose.

-

Footnotes:

-

[1] Rapid Epinephrine Administration Improves Early Outcomes in Out-of-Hospital Cardiac Arrest.
Koscik C, Pinawin A, McGovern H, Allen D, Media D, Ferguson T, Hopkins W, Sawyer K, Boura J, Swor R.
Resuscitation. 2013 Mar 21. doi:pii: S0300-9572(13)00175-5. 10.1016/j.resuscitation.2013.03.023. [Epub ahead of print]
PMID: 23523823 [PubMed - as supplied by publisher]

-

Koscik, C., Pinawin, A., McGovern, H., Allen, D., Media, D., Ferguson, T., Hopkins, W., Sawyer, K., Boura, J., & Swor, R. (2013). Rapid Epinephrine Administration Improves Early Outcomes in Out-of-Hospital Cardiac Arrest Resuscitation DOI: 10.1016/j.resuscitation.2013.03.023

.

Is Epinephrine a Rat Poison AND a Human Poison?

ResearchBlogging.org
-

Dr. Minh LeCong has been a proponent of epinephrine in cardiac arrest, but he is now realizing that the evidence in favor of epinephrine is weak, old, and limited to animal studies. In humans, the evidence for epinephrine is based on an unreasonable infatuation with the temporary production of a pulse.
 

I would like to believe that epinephrine/adrenaline is not harmful in cardiac arrest or other critical states. I have given so much of it over the years and on occasion believed it has saved lives. Certainly in anaphylaxis I have not doubt it saves lives. For cardiac arrest, cardiogenic shock, septic shock, what of those states?[1]

 

However, the evidence against epinephrine keeps accumulating.
 

Anesthetized rats received a single intravenous injection of epinephrine (25, 50, or 100 mcg/kg);[2]

 

 

What is the dose of epinephrine in pediatric cardiac arrest?

10 μg/kg (up to 1,000 μg, which is just the 1 mg dose in micrograms [mcg or μg]).

What would be the adult weight equivalent to 25 μg/kg?

40 kg (88 pounds).

This is less than one single dose of epinephrine in cardiac arrest, but we don’t stop at one dose any more than a junkie stops at one dose of heroin. 2 1/2 doses would be the equivalent for pediatric patients. 2 1/2 doses would also be the equivalent for a 100 kg (220 pound) adult.
 

Epinephrine injection in the intact animal caused hypoxemia, hypercapnia, and acidosis at all doses. Arterial oxygen tension was reduced within 1 min of injection. Hyperlactatemia occurred by 10 min after 50 and 100 mcg/kg.[2]

 

The patients we treat are already dead, so some people claim that we cannot make them any worse off, but we can.

Whatever chance they have at resuscitation can be decreased, or eliminated, by using the wrong treatment – anything other than continuous chest compressions and defibrillation. Nothing else has been shown to improve survival.

I know what some people are thinking –

We don’t usually give that much. When we do give that much, it is because the patient needed it. So what?

The problem with that approach is assuming a lack of harm because of a lack of explicit evidence of harm.

The authors did not test less than 25 μg/kg of epinephrine, so this does not provide clear evidence of harm, but it does add more evidence to the ever increasing list of studies showing that epinephrine (all catecholamines) can be very bad for the heart.
 

CONCLUSIONS:: Bolus injection of epinephrine in the intact, anesthetized rat impairs pulmonary oxygen exchange within 1 min of treatment. . . . These results potentially argue against using traditional doses of epinephrine for resuscitation, particularly in the anesthetized patient.[2]

 

Why is this being posted by someone who supported epinephrine use in cardiac arrest? Because Dr. Minh LeCong is using a scientific approach. He is not looking for evidence to support his biases, and we all have biases. He is looking for the truth, which does not care what we want the truth to be. That is the importance of evidence, which no amount of wishful thinking can overcome.
 

This is a turn around to my previous stance and reflects that one must follow the literature and read the patterns of where science and clinical practice are heading for the care of our critical patients.[1]

 

I agree, but I would not limit that to critical patients.

Harmful effects of treatments will be most noticeable with patients who are already critically ill, but can still harmful to healthy people.

For a nice short presentation on the use of catecholamines (epinephrine, dopamine, norepinephrine, dobutamine, et cetera), there is a recording of a presentation by Dr. Mervyn Singer at the 2009 Manchester Critical Care Conference. This is a free download and should be required listening for anyone who uses catecholamines in patient care.[3]

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Footnotes:

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[1] Epinephrine/Adrenaline is RAT POISON
PHARM – PreHospital And Retrieval Medicine
by rfdsdoc
September 22, 2012
Article

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[2] Epinephrine Induces Rapid Deterioration in Pulmonary Oxygen Exchange in Intact, Anesthetized Rats: A Flow and Pulmonary Capillary Pressure-dependent Phenomenon.
Krishnamoorthy V, Hiller DB, Ripper R, Lin B, Vogel SM, Feinstein DL, Oswald S, Rothschild L, Hensel P, Rubinstein I, Minshall R, Weinberg GL.
Anesthesiology. 2012 Oct;117(4):745-754.
PMID: 22902967 [PubMed - as supplied by publisher]

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[3] Catecholamines Should Be Banned
Mervyn Singer
2009-04-24-1545
6th Annual Critical Care Symposium
Manchester, UK
Page with link to free mp3 download from Free Emergency Medicine Talks

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Krishnamoorthy V, Hiller DB, Ripper R, Lin B, Vogel SM, Feinstein DL, Oswald S, Rothschild L, Hensel P, Rubinstein I, Minshall R, & Weinberg GL (2012). Epinephrine Induces Rapid Deterioration in Pulmonary Oxygen Exchange in Intact, Anesthetized Rats: A Flow and Pulmonary Capillary Pressure-dependent Phenomenon. Anesthesiology, 117 (4), 745-754 PMID: 22902967

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