Christopher, of My Variables Only Have 6 Letters, poses an interesting question in response to Amiodarone for Cardiac Arrest in the 2010 ACLS – Part II.
I wonder if Nexterone, the new formulation for amiodarone, would have any impact on these studies? Less cardiotoxic == better?
How do we know that the effects of amiodarone that are cardiotoxic are not responsible for the increased ROSC (Return Of Spontaneous Circulation) and survival to admission?
Maybe the cardiotoxic effects lead to both the improved ROSC and the increased in-hospital death.
Maybe, without the cardiotoxic effects, all amiodarone does is interfere with compressions.
We know that epinephrine depends on its cardiotoxic effects for increased ROSC.
We justify that temporary epinephrine toxicity, because we claim that epinephrine leads to improved short-term survival. We hope that improved short-term survival will lead to improved long-term survival. That improved long-term survival is something that only exists in theory, while the epinephrine toxicity is very real.
We would not give a 1 mg bolus dose of epinephrine to any patient having a STEMI (ST segment Elevation Myocardial Infarction), because we expect epinephrine to kill STEMI patients. Even if the epinephrine does not kill the patient, it will be expected to produce a lot of harm – permanent harm.
What do we do if our STEMI patient has a sudden onset of cardiac arrest on the way to cardiac catheterization?
We don’t even think about it. We give epinephrine.
Why?
Better to do something harmful, than to do nothing and appear ineffective.
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We seem to be deciding that we have a drug that is the answer, except for these nasty side effects that prevent the drug from demonstrating its bountiful goodness. We seem to be saying that this is a drug that is hiding its light under a basket, except that the AHA (American Heart Association) is shining a bunch of Klieg lights on some irrelevant ROSC results that do not live up to their promise.
Maybe the AHA is just another example of the drunk looking under the street light, because that is where the light is best, rather than looking where the evidence leads.
Maybe the answer does not come in a syringe.
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That’s something I hadn’t considered as well.
Perhaps the benzyl alcohol would be efficacious? Polysorbate 80? If I recall, those are the two diluents that are chiefly responsible for the cardiovascular effects seen after IV administration. Like the study you posted with IV NTG used in cardiac arrest with good success, maybe we should just be giving 120mg of benzyl alcohol/polysorbate-80!
I wonder how they can call them “diluents” when they are not pharmacologically neutral?
Christopher,
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My interpretation of this may be best summarized by a scene from perhaps the most important EMS movie.
The Keeper probably assumes that this arcane information is impossible to answer. He does not appear to to have any understanding of the material he is testing people about. This is not unusual in EMS.
We teach people to respond to many questions with just a number, or some other rote answer. How often do we teach people what the answer means? They can pass a multiple choice test as long as they can recognize the answer that was drilled into them. However, when questioned for details on this, they have no idea. With the polysorbate 80, we have an unknown, but we pretend that we understand the effects and use it as a placebo, even though we don’t believe that it is inert.
In animals, hypotension (hypotension has been attributed) to its diluent, polysorbate 80.
Based on 7 dogs.
commercial intravenous amiodarone produces results different in dogs than has been previously reported in humans.
A whole bunch of Maybe or What? I don’t know that! Auuuuuuuugh!
We are basing treatment on interpretations of interpretations and concluding that the treatment is safe and beneficial, even though the study does not support this conclusion.
This is not good medicine, but it is the standard of care.
Well I’m certain that they’ve consulted the Book of Armaments and found the safety studies for amiodarone required by the FDA…although if I recall amiodarone was accepted without these by the FDA because of pressure placed since Europe had already allowed it?
Or am I mistaken?
Christopher,
I do not know what the FDA used for approval, but I expect that it was approved for treatment of arrhythmia, possibly atrial fibrillation, and is used off-label for cardiac arrest. OTOH, how much is required to show that it does not make dead people worse?
You are guaranteed to be mistaken, when you ask that question. Either you were originally mistaken, or your suggestion that you were mistaken is mistaken. 😉