Medical Myths - Toxicology Mythbusting

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Nurses Edition Commentary

Mizuho Morrison, DO, Kathy Garvin, RN, and Lisa Chavez, RN

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The flumazenil portion of this discussion sends the wrong message, and may send listeners down an unnecessarily dangerous path. If providers reserve flumazenil use for the context of a likely sedative hypnotic overdose (acute or chronic) which is severe enough where they're considering intubating for airway protection, then the risk benefit ratio strongly favors flumazenil.

If that's the scenario we're working from, where intubation and mechanical ventilation is the likely next course of action, then here's the decision tree:
1) I intubate the patient and accept the known morbidity associated with it
2) I use flumazenil...
2a) It works and I don't need to intubate
2b) It doesn't work and I need to intubate
2c) It causes the rare complication of a seizure, and I need to intubate

We're literally lost nothing with a flumaenil trial other than a few minutes to draw it up and give it. If you're about to intubate anyway and your antidote either doesn't work or causes seizure, your next step is exactly where you were in the first place.

Three other things about the conversation regarding flumazenil-induced seizures bothers me:
1) It's a relatively rare complication (see the papers Bryan recommends, including the 2016 one)
2) Flumazenil is a competitive inhibitor, so benzos still might work for seizures, just in higher doses
3) If benzos don't work, then we move on to propofol, barbs, etc. Does flumazenil somehow suck the seizure treatment algorithm out of our EM providers' brains? If not, then a flumazenil-induced seizure should not be intractable and resistant to their otherwise effective management

-Sam Stellpflug

Anand S. -

Hey guys. Here's a response from Bryan:

Thanks for your comments. The EMRAP discussion was focused on interpreting/misinterpreting recent literature on flumazenil, not on the nuances of its use or providing strong opinions one way or another. While we did not mention specific scenarios, I did state that even with the meta analysis results, the risks and benefits should be weighed in a given situation. The imminent intubation scenario you describe is one of them. Cardiac arrest from a suspected benzodiazepine (probably with other agents on board) is another. The benefits also often outweigh the risks when reversing procedural sedation, for iatrogenic overdose, or in pediatric benzodiazepine poisoning. The algorithm you propose is excellent, in part due to the potential risks of intubation/mechanical ventilation.

Another point you raised was that benzodiazepines could in fact be used after flumazenil, but in larger doses to overcome the competitive inhibition. This is 100% true. However, the binding affinity of flumazenil for the benzodiazepine receptor far surpasses the affinity of the benzodiazepines we would use to break a seizure (or other withdrawal signs/symptoms). Not many would be comfortable using the doses required, particularly after just using a drug to reverse the initial overdose. Phenobarbital or propofol are other options, as you recommended. I was simply stating that the first line agent of choice, a benzodiazepine, would likely not be an option.

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