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What evidence did the AHA (American Heart Association) use to decide to keep epinephrine (adrenaline) in the 2010 ACLS (Advanced Cardiac Life Support) guidelines?
Since most drug trials have, at most, demonstrated only short-term outcome advantage, it may be important to evaluate long-term outcome when these drugs are combined with optimized post–cardiac arrest care.[1]
Let me translate that –
We have only looked at short-term outcomes (ROSC – Return Of Spontaneous Circulation), perfusion pressure, and other surrogate endpoints.
We have never done a study large enough to find out if epinephrine works.
Even though surrogate endponts are only a preliminary basis for treatment, we refuse to insist on better evidence to continue with this uncontrolled, unapproved experiment on patients.
We have been pumping dead people full of epinephrine according to ACLS since 1974 and only now think that it may be important to evaluate long-term outcome.
What have we been waiting for?
Where is our ethical obligation to patients?
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Based on this complete failure to show that epinephrine produces any improvement in outcomes that matter, what does the AHA recommend?
Treatment Recommendation
Although there is evidence that vasopressors (epinephrine or vasopressin) may improve ROSC and short-term survival, there is insufficient evidence to suggest that vasopressors improve survival to discharge and neurological outcome. There is insufficient evidence to suggest the optimal dosage of any vasopressor in the treatment of adult cardiac arrest. Given the observed benefit in short-term outcomes, the use of epinephrine or vasopressin may be considered in adult cardiac arrest.[1]
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We should stop and reconsider our complete failure to improve survival with drugs. We should not keep procrastinating.
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Given the observed benefit in short-term outcomes, the use of epinephrine or vasopressin may be considered in adult cardiac arrest.
How can we ethically come to that conclusion?
This is the kind of fraud that is used to justify homeopathy, Reiki, acupuncture, and every other kind of alternative medicine.
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Knowledge Gaps
Placebo-controlled trials to evaluate the use of any vasopressor in adult and pediatric cardiac arrest are needed.[1]
And they are long overdue.
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What if we look at it this way?
Given the absence of benefit in long-term outcomes,
the use of epinephrine or vasopressin
may be considered FUTILE in adult cardiac arrest.
The medical condition is cardiac arrest.
The goal is a Return Of Normal Life.
We have limited ourselves to just looking at Return Of Spontaneous Circulation for 36 years of ACLS guidelines.
How many people who take ACLS will be told that the strongest recommendation for epinephrine the AHA could come up with is really only that the use of epinephrine or vasopressin may be considered in adult cardiac arrest.
If I were writing an EMS protocol, this is the way I would use that suggestion from the AHA –
OK. I did consider epinephrine.
I considered that there is no evidence that in any way justifies automatically giving epinephrine to every cardiac arrest patient.
I could not ethically continue to include epinephrine in any treatment of cardiac arrest outside of a large scale randomized placebo-controlled trial that is designed to produce statistically significant results.
What do we hope for when we treat cardiac arrest?
Return Of Spontaneous Circulation.
Or –
Return Of Normal Life.
We are asking the wrong question and we are satisfied with an irrelevant answer.
We are dangerous.
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Footnotes:
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[1] Supporting the Circulation During Cardiac Arrest
2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations
Part 8: Advanced Life Support
Free Full Text from Circulation with link to PDF Download
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Just found out the novelty jinx remover is on manufacturer backorder… now what do we use?
David B,
We can always fake it.
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Faking it is also unethical.
Anonymous,
That depends on what we are faking.
If I am faking something in order to prevent harming a patient, faking it is much more ethical than harming the patient.
For the novelty jinx remover, there is no such thing as a genuine jinx, so there cannot be any genuine jinx remover, so a fake of something that does not exist is no less real than anything presented as genuine. If it is presented as fake, then it is more ethical.
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The difference being…
ROSC tends to be a useful starting point for return of normal life, even if it doesn’t always lead there.
Unless you know of a method of achieving return of normal life without first achieving ROSC? I’d be interested to hear it.
In the absence of any studies showing *diminished* return of normal life with adrenaline or other drugs that improve rates of ROSC, I would say that increasing ROSC is giving people the best chance of then taking the next steps along the path to return of normal life (or as I’ve seen it abbreviated – RONF – “return of neurological function”). And thus ethically, at least to my mind, adrenaline is a good idea.
Nonetheless, I agree with your main point. More research needed, and providers/governments/ethics committees/wherever the hold up is need to have the balls to do some proper adrenaline vs placebo studies!
I see where you’re coming from, and it’s a good point. That being said, if we know that giving epi/adrenaline/whatever gets us to a “starting point” but we know that it will, x amount of the time(being a significant number), provide us with what we assume is a good thing but turn into death is it really in the patient’s best interest?
That sounds almost like when EVERYONE did x, y, or z treatment because they knew someone who’d heard the medic from the next town over calling in a report where said treatment saved the guy and therefore it worked. If we want to go that route, let’s go back to giving aminophylline in cardiac arrest. what the heck, right?
If those x amounts of time was going to turn to death anyway, is it not in the patient’s best interests to give it a go?
And I’ll admit I had to look up aminophylline. The difference as I see it though, is that adrenaline isn’t a case of anecdotes, there is good evidence that it improves ROSC (where there isn’t evidence is if it produces better outcomes beyond that, and that’s where the research is needed).
JB,
You continue to assume that more ROSC equals more good outcome, even though there is no evidence to support that.
How much damage do we do to the brain and heart, just to be able to say we got a pulse back?
My full response to your comments is at -
The Danger of ROSC – Return Of Spontaneous Circulation
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Can’t say, clowns will eat me,
We are treating a condition that we only see for a short period of time. The patients who walk out of the hospital are small in number, so anything we see disproportionately affects our opinions. Do we go back and read the chart, when someone comes by to thank us for resuscitating them? Did we give them drugs, or did they have ROSC before we gave drugs?
We need to stop thinking of ROSC as a save.
ROSC is just a part of resuscitation and getting there with drugs appears to mean that we are not going to have a good outcome.
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ROSC may be a starting point, but ROSC from EPI is not. Most people who experience ROSC and survive do so without EPI, usually being defibrillated out of a shockable rhythm. For those who go down a different, EPI laced path to ROSC, there is no starting point, just an end point. How do we know this? Because if it were not the case, there would be better survival to discharge numbers after receiving EPI, but that improvement does not exist. That’s about as clear as it gets. We can confuse the issue with “starting points”, etc, but the bottom line is there is not improvement in survival to discharge from giving EPI.
David B,
You put that much better than I did.
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Yes.
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That may be the case. I think there may be a small subset of patients who do benefit from epinephrine, but they are being lost in the data showing the harm from epinephrine.
Epinephrine may be an intermediate point, but on a route to predominantly bad outcomes.
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Again, very well put.
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RM,
Firstly, have you approached your service with a proposal to conduct a random controlled trial comparing epinephrine vs a placebo? Like the objective of your blog maybe you need to lead this change by action and conduct some research.
Here within Australia, a number of us have been attempting to conduct a similar trial, however given the theoretical basis for the use of epinephrine within a cardiac arrest, ethics approval is withheld. It seems that because it is believed to work it would be unethical to withhold Epinephrine. However we need the ethical approval to show whether epinephrine may actually be harming our patients. Though with the years of using epinephrine with our observations and our theoretical knowledge, this all suggests and supports that epinephrine works.
Therefore it does come down to the sell. While we are talking about the sell, what the AHA/ILCOR are saying are very choice words. By stating that a service “may” choose to use epinephrine is inviting research to be performed. Generating some 2-3years worth of data that could be reported back to ILCOR/AHA to be considered for the 2015 Consensus. Though as my first point indicated, obtaining ethical approval is the biggest hurdle.
I hope that you and all your readers had a great Christmas and are looking forward to a great New Year.
DR.
Dennis,
You’ve seen the PACA trial from Western Australia, right? It’s exactly what you’re talking about. It was originally supposed to be multi-site, multi-agency etc, and I believe it got ethics approval but was then shut down everywhere other than WA for political reasons.
Interesting research nonetheless.
JB
Yes that is right. And as I understand it another hurdle was obtaining approval from the industry union and a commitment from the Local Governments (who budget and fund the EMS services) to recognise the potential success of the study as a productive gain for Enterprise Bargaining negotiations.
This is the politics that is hindering the scientific advancement of EMS within Australia. So not only do we have to convince the Ethics boards but the politicians and our Union representatives.
DR
Denis Roscoe,
The ethical boards did originally give approval. It was the politicians who withdrew approval.
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It is bizarre that the authors conclude that the results of this study in any way support the use of epinephrine.
At best, 4% survival to discharge is not a goal for resuscitation. Their response times are more than 10 minutes, so that may be the limiting factor, but 4% is not a goal.
In the Norwegian study, 12% of the no adrenaline group survived for at least one year after discharge, while only 6% of the adrenaline group survived for at least one year after discharge.
There are three things that seem to change with use of epinephrine –
Epinephrine moves the location of death to the hospital.
Epinephrine dramatically increases the cost of treating those deaths.
Epinephrine dramatically decreases survival one year after cardiac arrest.
How can such treatment be ethical?
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JB,
That was very disappointing. The results, if conducted as planned, might have provided some answers. It is unfortunate that they ran out of funding and ran into some political backlash from people who do not understand medicine.
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Denis Roscoe,
The only studies likely to be useful are multi-agency trials. I keep hearing that ROC (the Resuscitation Outcomes Consortium) is working on this, but the last time I checked to see if there were any prehospital studies of epinephrine (adrenaline) in cardiac arrest, there were no studies in progress.
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Since it is based only on theory, research should be mandatory. Epinephrine does produce more ROSC (Return Of Spontaneous Circulation), but also appears to produce several times as many patients dying in the hospital and more neurological disability in those who survive to discharge.
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Not at all.
The only thing unethical is that people who do not understand medicine are making medical decisions.
Epinephrine has never been shown to work, until that changes, epinephrine is just an experimental drug that has snuck through the back door and become the Standard Of Care.
If we allow the Standard Of Care to prevent us from learning what works, it is just a Standard Of Abuse.
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We do not need these restrictions based on false ethical conduct. There is nothing ethical about forcing patients to be treated with drugs that are probably harmful and withholding that information from the patients.
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Not according to the people who write the guidelines –
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Yes, getting the approval of the ethics committees is a huge hurdle, but it can be done. We just need to get them to understand that continuing with unproven treatment and without any notification of the community that they are being treated with an unproven treatment is not ethical. This is not exactly a parallel of the Tuskegee experiment, but not that mush different, since we are only pretending to be providing effective treatment.
Is a pretend treatment that much different from no treatment?
If epinephrine does turn out to be harmful, is providing a pretend treatment that causes real harm in any way ethical?
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Likewise.
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