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

- Rogue Medic

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]

Footnotes:

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

[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]

[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

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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