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

- Rogue Medic

Wide variability in drug use in out-of-hospital cardiac arrest: A report from the resuscitation outcomes consortium – Part II

ResearchBlogging.org
 

Only low dose epinephrine was shown to improve ROSC (Return Of Spontaneous Circulation) in this study, but even low dose epinephrine dramatically decreased survival. I looked at that in Part I. Here I look at some of what the authors have to say about this in the discussion.

What seems most surprising is how bad the results were for epinephrine.
 

There was an inverse association between epinephrine dose and survival to discharge (Fig. 3). This relationship persisted after adjusting for age, gender, EMS witnessed arrest, bystander witnessed arrest, bystander CPR, shockable initial rhythm, time from 911 to EMS arrival, the duration of OHCA and study site.[1]

 

There appears to be only one thing that is relevant that was not controlled for – quality of CPR. The much worse quality of the Accentuate the ALS pre-2005 guidelines vs. the newer emphasis on compressions.

Here is a graph that shows the trend a bit differently from the graphs I included in Part I. Patients who received even 1 mg epinephrine had significantly worse survival to discharge.
 

 

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

 

Everything, no matter how natural, is poisonous.

Epinephrine naturally occurs in the body, but that does not make it safe to add more? Potassium occurs naturally in the body and potassium is used to execute people. Are we doing the same with some doses of epinephrine?

The graph seems to make it clear that the more epinephrine we give, the worse the outcomes. If any of us are still in favor of using epinephrine routinely in cardiac arrest, why aren’t we studying lower doses to see if we can find some dose that is less poisonous?
 

Despite the publication of guidelines designed to help standardize the management of OHCA there is substantial variability in the administration of drugs.[1]

 

The people who keep claiming that epinephrine (and other standards of care) should not be studied would be disappointed to find out that there is not universal use of their standards.

Is there any evidence that the EMS organizations that do not use these standards of care are sued at a higher rate than the EMS organizations that slavishly require that every ALS suggestion from the ACLS (Advanced Cardiac Life Support) guidelines be considered a standard of care?
 

The overall lack of evidence in favour of any pharmacological agent administered during CPR may result in different interpretations of the guidelines.[1]

 

Yes, these are guidelines and they are open to interpretation.

This is not shocking. What is shocking is that so many people do not understand that medical treatment is not about blindly following ancient ideas at the expense of our patients.
 

The early benefits of many of these drugs may be offset by later detrimental effects following resuscitation.[1]

 

I would word that differently.

The early appearance of benefits of many of these drugs may be offset by later detrimental effects following resuscitation.

ROSC is a surrogate endpoint and therefore only useful until larger studies can be done to find out if there is any benefit from the drug and whether that benefit may lead to improved outcomes.

A change in vital signs is not an improved outcome.
 

Relatively small benefits of drugs, especially among the minority of patients with VT/VF, may require very large sample sizes to be demonstrated.2 [1]

 

Yet we keep being told that it is unethical to study these treatments that have never been subjected to even the same requirements as thalidomide.
 

In addition, there are no Class I indications for any pharmacological agents during ALS which likely results in a substantial variability in the incorporation of guidelines into agency protocols.[1]

 

What class is epinephrine in cardiac arrest?
 

Class I
Benefit >>> Risk
Procedure/treatment or diagnostic test/assessment should be performed/administered.
 

Not Class I.
 

Class IIa
Benefit >> Risk
It is reasonable to perform procedure/administer treatment or perform diagnostic test/ assessment.
 

Not even Class IIa.
 

Class IIb
Benefit Risk
Procedure/treatment or diagnostic test/assessment may be considered.
 

There it is epinephrine is just above Class III – the category for things we should not do.
 

Class III
Risk Benefit
Procedure/treatment or diagnostic test/assessment should not be performed/administered. It is not helpful and may be harmful.
 

Ideally all CPR and ECC recommendations should be based on large prospective randomized controlled clinical trials that find substantial treatment effects on long-term survival and carry a Class I or Class IIa label.[2]

 

Epinephrine is not even Class IIa.

Perhaps Class IIb should be represented this way –

Wishful Thinking >>> Evidence
 

Drug Therapy in VF/Pulseless VT
When VF/pulseless VT persists after at least 1 shock and a 2-minute CPR period, a vasopressor can be given with the primary goal of increasing myocardial blood flow during CPR and achieving ROSC (see “Medications for Arrest Rhythms” below for dosing) (Class IIb, LOE A).
[3]

 

LOE A?

LOE is Level Of Evidence. A is the highest ranking of evidence.

That means that the AHA (American Heart Association) is confident that they have excellent evidence, but that the evidence is not enough to give anything more than their weakest recommendation for use.

This Class IIb recommendation remains unaffected, even though the studies published continue to be neutral or negative.

When do we admit that we have been fooling ourselves?

Why does this long shot remain the routine treatment in most places?

Looking at the graph of the different doses of epinephrine, maybe we should be interpreting the results as 3 mg = time to terminate resuscitation.
 


 

Epinephrine.

Cause of death, or just an indicator?

Either way, epinephrine not supported by good evidence.
 

Expert recommendations must come with an expiration date.

Footnotes:

[1] 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; Resuscitation Outcomes Consortium Investigators.
Resuscitation. 2012 Nov;83(11):1324-30. doi: 10.1016/j.resuscitation.2012.07.008. Epub 2012 Jul 31.
PMID: 22858552 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central.

[2] Guidelines and Treatment Recommendations
2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Part 1: Introduction
Free Full Text

[3] Drug Therapy in VF/Pulseless VT
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Part 8: Adult Advanced Cardiovascular Life Support
Part 8.2: Management of Cardiac Arrest
Free Full Text from Circulation

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 (2012). Wide variability in drug use in out-of-hospital cardiac arrest: A report from the resuscitation outcomes consortium. Resuscitation PMID: 22858552

.

Speak Your Mind