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antidote, EM best practice, antidote derangement syndrome, toxicology

I love the Oxford English dictionary definition of antidotea medicine given to counteract the influence of poison or an attack of diseasebecause it is subtly correct. It suggests that an antidote is given with the belief that it will successfully treat a poisoning.

It does not imply that the antidote will treat the poison, reverse toxic effects, or be necessary to improve clinical outcome. Taken literally, it implies that the concept of antidote is, like Santa Claus or the Tooth Fairy, a matter of belief, not necessarily fact.

I'd propose a second definition of antidote from the Gussow Dictionary of Rational Toxicology: something that stops all critical thinking and provides clinicians with a false sense of security in medical toxicology cases.

Not infrequently, we at the poison center find that a physician, having learned that drug B is the antidote to poisoning from substance A, becomes stubbornly fixated on administering antidote B, even before asking some critical questions:

Too often, it's easy for the physician to feel that his job is done and the patient is out of danger once an antidote is given. This misconception can lead the medical team to lessen its attention to basic supportive care and careful monitoring. An antidote is not magic; it is just one more thing in the medical toxicologist's toolbox that may or may not be helpful in a specific situation.

Take glucagon, a counterregulatory hormone moderating the effects of insulin by increasing blood glucose. It is synthetized in pancreatic a-cells, and has long been considered an antidote to beta-blocker poisoning because it increases myocardial cAMP though the actions of specific glucagon receptors that are separate from the adrenergic b pathway.

But does the use of glucagon in beta-blocker poisoning actually improve clinical outcomes? This has not been well studied. Early animal research and case reports suggested that it might improve some hemodynamic parameters such as heart rate. But this has never been evaluated in controlled clinical trials. It is also important to realize that most of that research was done prior to 1998 and used glucagon derived from cow or pig pancreas. These preparations contained insulin. It is not clear to what extent that insulin affected the results and case outcomes.

Aside from the lack of convincing evidence of clinical efficacy, additional potential problems arise with administering glucagon. First, bolus doses frequently cause significant nausea and vomiting, not a good development in patients who may be bradycardic or have decreased mental status.

Second, glucagon has a very short duration of action10 to 20 minutesmeaning that a post-bolus infusion will be necessary to maintain its effect. Third, glucagon is surprisingly expensive. The acquisition cost of a 1 mg IV dose is $180 to $280, so administering a 10 mg bolus followed by an infusion of 10 mg per hour quickly adds up to real money. Many hospitals do not stock enough of the drug to treat even a single patient effectively because of the expense.

A recent systematic review on beta-blocker poisoning concluded that glucagon appears to have a minimal effect on improving hemodynamics, and proposed a management scheme that did not include glucagon at all, focusing instead on supportive care with fluids, atropine, and pressors. (Clin Toxicol [Phila]. 2020;58[10]:943.) An even more recent survey of cardiotoxic medication poisoning noted, Although glucagon has been touted as the traditional antidote to beta-blocker poisoning, evidence supporting its use is limited. The authors suggested, however, that it may be useful in treating small accidental overdoses of beta-blockers, or as a transient therapy to bridge patients to more definitive therapies. (Emerg Med Clin North Am. 2022;40[2]:395.)

The bottom line: Glucagon has several significant adverse effects but has not been proven to improve clinical outcomes in beta-blocker poisoning. It seems to be more effective at increasing heart rate than optimizing hemodynamics. It is not mandatory in all cases of beta-blocker overdose and is never definitive treatment. Considering it an antidote can lead to faulty clinical decision-making.

I have discussed other examples of antidote derangement syndrome in previous columns, noting that some online medical databases list cyproheptadine (Periactin) as an antidote for serotonin syndrome, and some clinicians fixate on using it in all such cases. Its clinical efficacy has not been demonstrated, however, and it has no established dose regimen. (No Evidence Supports Using Cyproheptadine for Treating Serotonin Syndrome. EMN. 2020;42[10]:18; https://bityl.co/Cmuk.)

High-dose insulin was introduced as an antidote to calcium channel blocker toxicity, and most cases of significant overdose back then involved verapamil and diltiazem, both of which are predominantly myocardial depressants. Today, the majority of overdoses at our poison center involve amlodipine, which is primarily a vasodilator. High-dose insulin is an inotrope but not a vasopressor, and it dilates blood vessels. (The Truth about High-Dose Insulin. EMN. 2021;43[12]:5; https://bityl.co/Cmul.) The use of the term antidote covers over this nuance.

We should abandon the term antidote. It often leads to muddy thinking. These drugs may or may not be indicated in specific circumstances. It's our job to think this through and determine optimal treatment for the patient in front of us.

One more definition: Antidote derangement syndrome refers to clinical decision-making induced by the delusion that the term antidote is synonymous with panacea.

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Dr. Gussowis a voluntary attending physician at the John H. Stroger Hospital of Cook County in Chicago, an assistant professor of emergency medicine at Rush Medical College, a consultant to the Illinois Poison Center, and a lecturer in emergency medicine at the University of Illinois Medical Center in Chicago. Read his blog atwww.thepoisonreview.com, follow him on Twitter@poisonreview, and read his past columns athttp://bit.ly/EMN-ToxRounds.

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