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Hey #medtwitter, let's talk about physostigmine.
Suppose you have some patient come in with a reported history of diphenhydramine ingestion. They're agitated, picking at things, mumbling, trying to get out of bed, etc.
#FOAMEd #FOAMTox
Suppose you have some patient come in with a reported history of diphenhydramine ingestion. They're agitated, picking at things, mumbling, trying to get out of bed, etc.
#FOAMEd #FOAMTox
You can do one of a few things at this point:
1) Ignore it, let the nurses redirect
2) Give benzos
3) Give some other sedative (antipsychotic, usually)
4) Give physostigmine
Which are you going to do?
1) Ignore it, let the nurses redirect
2) Give benzos
3) Give some other sedative (antipsychotic, usually)
4) Give physostigmine
Which are you going to do?
Most people will probably choose option 2 (benzos) but we'll see what the poll shows.
We're going to walk through why that's what is typically done, and why that's not the ideal approach.
We're going to walk through why that's what is typically done, and why that's not the ideal approach.
But first, just by way of explanation: anticholinergic toxidrome (more appropriately antimuscarinic toxidrome) occurs when muscarinic acetylcholine receptors are blocked. You get things like dry/flushed skin, urinary retention, dilated pupils, delirium, tachycardia, etc
This pic by awesome tox artists Kloss and Bruce is a good summary:
Because of the delirium, they can be difficult to manage. They often require a lot of nursing redirection, and often heavy doses of benzodiazepines or antipyschotics to get them to stay put. The reason for this? Those drugs don't treat the delirium directly, they just suppress it
And in the case of antipsychotics, if you pick the wrong one (such as olanzapine or quetiapine) they can actually make it worse. Some antipsychotics have antimuscarinic properties and will just make the delirium worse.
Enter physostigmine - an acetylcholinesterase inhibitor.
More ACh in the synapse -> more ACh at the muscarinic receptors, overcoming the antagonism from the drug, reversing the delirium. So when do you give it? The indication is in the trade name: Antilirium
More ACh in the synapse -> more ACh at the muscarinic receptors, overcoming the antagonism from the drug, reversing the delirium. So when do you give it? The indication is in the trade name: Antilirium
Physostigmine is ONLY indicated for the reversal of antimuscarinic delirium. You don't treat seizures with it. You don't treat cardiac toxicity with it. Only delirium.
Why would you want to treat the delirium? A few reasons
Why would you want to treat the delirium? A few reasons
- Diagnostics: if pt improves with physo, Dx is established
- Therapeutics: if pt requires pharmacologic management of delirium to support nursing efforts or for pt comfort, then reasonable to give it
- Avoid escalating doses of benzos and attendant risk of intubation
- Therapeutics: if pt requires pharmacologic management of delirium to support nursing efforts or for pt comfort, then reasonable to give it
- Avoid escalating doses of benzos and attendant risk of intubation
So why is this not already the standard of care? A few reasons:
- If pushed fast, physo can cause seizures. *Rarely* a problem if given slowly enough
- Provider comfort
- One pub from 1980 showing asystole after physo in the setting of TCA tox: https://pubmed.ncbi.nlm.nih.gov/7001962/
- If pushed fast, physo can cause seizures. *Rarely* a problem if given slowly enough
- Provider comfort
- One pub from 1980 showing asystole after physo in the setting of TCA tox: https://pubmed.ncbi.nlm.nih.gov/7001962/
Because of that article, it became standard to avoid physo if TCA tox was in the differential, or in the setting of QRS prolongation (and thus ?Na channel blockade from possible TCA).
Problem: this was a classic post hoc, ergo propter hoc fallacy.
Problem: this was a classic post hoc, ergo propter hoc fallacy.
Both patients had taken a lethal dose of TCA. Neither got bicarb (the current standard of care) before physo. These patients had treatment priorities other than reversing their delirium. We wouldn't even go there with them today - too sick
So, how do you give it?
First, you should have reasonable suspicion that the cause of the patient's delirium is an anticholinergic toxidrome. Make sure they have no cholinergic findings: wheezing, bradycardia, sweating, vomiting, etc.
First, you should have reasonable suspicion that the cause of the patient's delirium is an anticholinergic toxidrome. Make sure they have no cholinergic findings: wheezing, bradycardia, sweating, vomiting, etc.
Second: check for QRS prolongation.
Depending on who you talk to, QRS prolongation is either an absolute or relative contraindication to physo. My thought on this is that it might just signify you should have other treatment priorities (e.g. bicarb)
Depending on who you talk to, QRS prolongation is either an absolute or relative contraindication to physo. My thought on this is that it might just signify you should have other treatment priorities (e.g. bicarb)
Third: make sure your patient doesn't have a salicylate allergy. Physostigmine is formulated with salicylate as the anion, and although the amount is small, it's technically poor form to give a patient a med they're allergic to
Fourth: at least consider pre-treating with a small dose of lorazepam. Especially if they have QRS prolongation, this may reduce the risk of seizure even further than pushing it slowly would alone.
*This practice is controversial, and debated among toxicologists
*This practice is controversial, and debated among toxicologists
Fifth: if you choose to administer, be at bedside! Atropine should be close at hand, either in the room or in a code cart whose location you know
Give 1-2mg over 5-10 minutes, constantly watching for cholinergic findings. If they get bradycardic, sweaty, wheezy, or vomit-y, stop
Give 1-2mg over 5-10 minutes, constantly watching for cholinergic findings. If they get bradycardic, sweaty, wheezy, or vomit-y, stop
If it works, that's great! Diagnosis confirmed. Take this opportunity to ask them if they overdosed on any other drugs.
It's likely that they'll get delirious again. Physo can be re-dosed as necessary to clear sensorium
It's likely that they'll get delirious again. Physo can be re-dosed as necessary to clear sensorium
If you want to do some further reading on this, see this awesome blog post by @jonbcole2 on @ToxAndHound: https://emcrit.org/toxhound/physostigma/
And if you're with me this far, maybe you're interested in some primary literature, in which case go here:
https://pubmed.ncbi.nlm.nih.gov/30747326/
https://pubmed.ncbi.nlm.nih.gov/28703024/ https://pubmed.ncbi.nlm.nih.gov/29956570/
https://pubmed.ncbi.nlm.nih.gov/30747326/
https://pubmed.ncbi.nlm.nih.gov/28703024/ https://pubmed.ncbi.nlm.nih.gov/29956570/
Shout out to @Annie_Arens and @throwinbos, the first authors on the above papers
