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

- Rogue Medic

Epinephrine in Cardiac Arrest

 

One of the contradictions of emergency cardiac care is epinephrine. Epinephrine is the stimulant to counter death. If your heart has stopped this will get it beating again. Epinephrine has been in the ACLS guidelines as the first IV drug since the first ACLS guidelines.

Epinephrine must be very good.

Let me show you all of the research that demonstrates a significant improvement in survival to discharge from the hospital with a good neurological outcome.

Good neurological outcome?

Good neurological outcome means the patient leaves the hospital without losing so much brain function that he is no longer aware of anything, such as the fact that he is alive.

Here is the research, look closely:
 


 

There isn’t anything there – just a black hole full of nothing.

Abysmal.

The AHA (American Heart Association) would not have us continuing to use this treatment if there were nothing to justify the treatment, would they?

Well, the use of epinephrine is based on expert opinion. Expert opinion was about all that was available 30 years ago, so that was considered to be good enough back then.

And it’s not any more?

Now there is much better evidence available for consideration when evaluating the effectiveness of a drug for a specific condition.

The AHA lists the levels of evidence this way:[1]
 


Click on image to make it larger.
 

I don’t see expert opinion on there.

Expert opinion fits in near the bottom there. A little bit higher than the CNN articles about brain-dead people recovering,[2] but not much.

So, expert opinion is useless?

No, but anyone worth being referred to as an expert is going to use high quality evidence in making decisions.

OK, but there has to be research on epinephrine.

Of course there is. Epinephrine is one thoroughly studied drug.

That’s good. You had me worried that this was not being studied and just had expert opinion supporting it.

Let me quote from the AHA guidelines again:
 

To date no placebo-controlled trials have shown that administration of any vasopressor agent at any stage during management of pulseless VT, VF, PEA, or asystole increases the rate of neurologically intact survival to hospital discharge. There is evidence, however, that the use of vasopressor agents favors initial ROSC.>[1]

 

ROSC?

Return Of Spontaneous Circulation.

It means that the patient has a pulse that once again can be felt by medical personnel. This is after a time where no pulse could be felt.

You mean the patient is alive again.

Not necessarily. The patient may have had a pulse that you could not feel before, but now you can feel the pulse again.

So the patient is better?

Maybe. This is the thing that seems to confuse a lot of people – including the doctors.

So the patient isn’t better?

It isn’t that simple.

Why not, the patient is better or the patient is not better.

Better means that the patient is more likely to leave the hospital and be a functioning human being – at least one that does more than take tube fed food and water and turn it into feces and urine. Someone who recognizes that there is another person in the room, maybe even recognizes who that person is.

OK, but they have to get a pulse back to have a good outcome.

Yes, they do. And we should help to get that pulse back in the least destructive way possible.

How can getting a pulse be destructive? The patient is alive now.

OK, then why do you have more patients with ROSC with epinephrine, but you don’t have more patients leaving the hospital neurologically intact?

Well, if more patients get pulses back with epinephrine, but the same amount leave the hospital neurologically intact, doesn’t that mean that a higher percentage of epinephrine patients are doing worse in the hospital?

That is one way of looking at it.
 

They noted that in animals the use of epinephrine in cardiac arrest resulted in a significantly increased severity of postresuscitation myocardial dysfunction and a decrease in the duration of postresuscitation survival. Further, these animals required a larger number of electrical countershocks to achieve successful conversion to a viable rhythm and return of spontaneous circulation.[4]

 

Of course, that is just from animal studies. There aren’t any human studies that show it is dangerous?

Well, what if we look at a study in humans with a positive outcome.
 

Epinephrine use (1.84; 1.23-2.78) and age (1.02; 1.01-1.03) were independently associated with risk of death after day 1. The proportional hazards assumption was satisfied.[5]

 

By epinephrine leading to increased risk of death after day 1, these poets mean that these patients lived longer. This is presumed to be a good outcome.
 

Finally, the methods used to determine survival provided no means to evaluate neurological or functional outcome.[31]. Our primary intention with this analysis was to illustrate a new method for evaluating long-term survival after cardiac arrest. An important future direction is to apply these approaches to data sets that fill these informational gaps.[5]

 

The University of Pittsburgh Institutional Review Board granted a waiver from the requirement for informed consent for examination of these records until April 14, 2003, at which time this procedure was no longer allowed because of Health Insurance Portability and Accountability Act (HIPAA) legislation.[5]

 

Now the HIPAA legislation does have exemptions for billing, quality control, and (golly gee whiz) research. If this were their first study, maybe this would be excusable, but they are prolific researchers (as long as you have data that can be thrown into a computer and quantitatively analyzed).

This is not a way to evaluate quality, but they claim that their superficial methods do evaluate quality.

Here is the really odd part:
 

Time-to-death (days) after collapse was identified using the paramedic record, the social security death index or obituaries for adult (≥18 years) out-of-hospital cardiac arrest (OOHCA) cases from Pittsburgh, Pennsylvania between 1998 and 2002.[5]

 

Orwellian.

The Social Security Death Index?

Unless the government knows you are dead, you are considered to have been resuscitated with a good long term outcome from cardiac arrest.

That is absurd.

The other method of showing a good outcome with useless drugs is to compare one drug that is not effective in improving survival with another drug that is not effective in improving survival to see which one is better at improving survival, why do we care?

Neither drug makes things any better – they make things worse. Choosing to give the one that does the least harm is not as smart as just avoiding the harm from giving the drugs.
 

See also –

Dead VT vs Not Quite Dead, Yet VT.

More on Epinephrine in Cardiac Arrest.

Footnotes:

[1] TABLE 2. Levels of Evidence
2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Part 1: Introduction
Free Full Text from Circulation

[2] CNN is Selling Snake Oil – All You Have to Do is Believe.
Tue, 25 Mar 2008
Rogue Medic
Article

[3] Medications for Arrest Rhythms
2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Part 7.2: Management of Cardiac Arrest
Arrest Rhythms
Free Full Text from Circulation

[4] Prehospital management of cardiac arrest: how useful are vasopressor and antiarrhythmic drugs?
Wayne MA, Racht EM, Aghababian RV, Kudenchuk PJ, Ornato JP, Slovis CM.
Prehosp Emerg Care. 2002 Jan-Mar;6(1):72-80. Review.
PMID: 11789656 [PubMed – indexed for MEDLINE]

[5] Differential effects of out-of-hospital interventions on short- and long-term survival after cardiopulmonary arrest.
Wang HE, Min A, Hostler D, Chang CC, Callaway CW.
Resuscitation. 2005 Oct;67(1):69-74.
PMID: 16146669 [PubMed – indexed for MEDLINE]

.

Comments

  1. This is grim stuff.I thought medicine was “science”?

  2. I imagine it is tough to get IRB approval for that placebo controlled randomized double blind clinical trial. 😉

  3. Medicine is science in a bit of a different way from physics. You cannot be sure of the result when you give any medicine. There will always be idiosyncratic reactions to treatments.I am criticizing medicine as improperly applying the research that has been done and poorly choosing the methods used for much of the medical research. To involve patients in a study that leads nowhere, answers no significant questions, and has no real possibility of improving care is a waste. Too much of medical research is nothing, but a waste.Studies that are done are often so poorly designed that even a good hypothesis leads to meaningless research, because of that poor study design.I will write more about this.

  4. Vince, you know that the IRBs have approved this stuff in the past.By refusing to study treatments properly, they are essentially continuing uncontrolled experimentation on patients with only retrospective review as a means of evaluating the treatment that is considered to be the standard of care by the IRB rocket surgeons.

  5. Good replies, RM.. I’m looking forward to learning more.And, it would be GREAT if these studies could be improved! As I age, I expect I’ll be interacting more with the good doctors, and I have high hopes of getting knowledgeable treatment.

  6. edwin, The studies of epinephrine vs. placebo are mostly done overseas, where there are not so many fears of legal repercussions. Most of the studies done in the US are only comparing epinephrine with a competitor – vasopressin is the drug of choice, now.The AHA is improving its focus on research. Their last change in ACLS guideline was dramatic. It was research based, but did not go far enough, in my opinion.I am just contributing in my own charming idiom to the way people look at the research.

Trackbacks

  1. […] that causes arrhythmias. I describe problems with the use of epinephrine in Epinephrine in Cardiac Arrest, More on Epinephrine in Cardiac Arrest, and Dead VT vs Not Quite Dead, Yet […]

Speak Your Mind