4/ Back to the poll choices:
1️⃣ is the VPA being chewed up by fPHT?
I’m sure @theABofPharmaC & @jimmySuhMD are going to do an incredible collab about VPA & PHT.
🛑Spoiler: they do not play nicely together.
5/ In short: VPA displaces PHT from plasma protein binding sites
This significantly ⬆️ FREE phenytoin (as it did in this case, see ⬇️).
But you might not detect this if you are just monitoring TOTAL phenytoin levels, which can stay the same or EVEN DECREASE!
6/ But PHT can also ⬇️ VPA, and the effect is unpredictable.
So -- This is a plausible explanation, but the DRAMATICALLY low VPA would be a bit unexpected.
VPA+fPHT is just a headache. If you really must use, follow free levels closely.
7/ 2️⃣ Is it VPA and warfarin?
No. [Obvi] this patient’s warfarin had been reversed before the burr holes…
But VPA + warfarin can cause issues:
🌟VPA can ⬆️ warfarin by ⬇️ protein binding.
🌟VPA is also an inhibitor of CYP 2C9 = ⬆️ Warfarin
8/ Thanks @MeganRx1 for putting together this awesome chart for the #acuteneurologysurvivalguide. (BTW I swear is going to be published in 2022, hopefully by springtime…).
As you can see warfarin + AEDs also = headache.
9/ So DOACS for patients on AEDs then?
Sadly, those can be tough too. PHT, PHB, & CBZ sig induce the metabolism of DOACs and may result in therapeutic failure.
🛑 Avoid combination of PHT, PHB, or CBZ with DOAC anticoagulants 🛑
10/ 3⃣Was it just VPA wasn’t being absorbed?
Well that would have been true given the state of the gut ⬇️😳But, the VPA was being given IV.
I know that its pentobarbital that gets the bad rap for GI issues, but I find that ileus is a frequent #statusproblem even w/o this med
11/ 4⃣Carbapenem + VPA?
🛎️Bingo!
Carbapenems hate VPA, the whole VPA treatment.
Now, please don’t ask why, no one quite knows the reason.
14/ Finally - The other issue that comes up with VPA is that about ~35% of patients develop hyperammonemia.
Mechanism involves a decrease in carnitine serum concentration (I’m sure @capt_ammonia could explain)!
15/
*Most* pts are asymptomatic, but hyperammonemia encephalopathy/cerebral edema can develop requiring IV L-carnitine 100mg/kg IV x1 f/b 15mg/kg Q4-6H (dosing from peds lits) pubmed.ncbi.nlm.nih.gov/17496767/
For asymptomatic pts can use PO l-carnitine 1000-3000mg/day in divided doses.
16/ Take aways: VPA is a great sz drug but:
💥Does not play nicely with PHT or warfarin
💥Can disappear with even a single dose of a carbapenem
💥Commonly causes hyperammonemia which is usually asymptomatic, but not always
⏸️Use with caution & monitoring in the critically ill.
One day I am going to write a typo-free tweetorial with no misplaced links, no formatting/line issues, no mis-numbered tweets... that day was not today😂.
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1/ 🥳Big News! This is the 1⃣0⃣0⃣th #CONTINUUMCASE!!
To celebrate? A must know dz, bc w/ this disease:
Time is Spine!
A 39 yo woman with Sjogren’s syndrome comes to the ED with sudden neck pain. Then arm weakness. Then leg weakness. All within 24 hours.
Now she can’t urinate
2/ On your exam, mental status=intact. But she has terrible vision in the right eye, which she reports is from a sjogrens attack.
She has 3/5 arm strength, 2/5 leg strength.
As shown above 🔼 she has a longitudinally extensive lesion w/ contrast at C2 and C3.
Is this Sjogrens?
3/ You complete a spinal tap.
‼️There are 120 WBC with a lymphocytic predominance‼️
A 58 yo woman with breast cancer on active chemo presented with shortness of breath.
She was just found to have (A).
Unfortunately, a head CT reveals (B).
They want to know – can she be a/c’ed? A #ContinuumCase
2/ Thoughts?
3/ Why does this feel like such a common conundrum? A few reasons.
1⃣incidence of brain mets may be 🔼 due to improved detection & better control of extracerebral dz
2⃣VTE is common in cancer patients & may also be 🔼 (more detection, longer life expectancy & novel treatments)
1/ A 35 yo M has lower limb weakness & painful hand & foot paresthesias.
EMG suggested axonal neuropathy and a presumed diagnosis of GBS was made.
After PLEX he was not better, instead he was becoming confused & ataxic.
How might a Thanksgiving Turkey solve this #ContinuumCase?
2/ Note: PLEX does not work immediately. In fact, many pts fail to have a response to immunotherapy during their hospitalization. Many continue to progress DESPITE treatment.
This does not mean that the treatment isn’t working. More is not better!
3/ Ok, off my soap box!
As you should for all confusing cases, you go back to the bedside and the patient tells you that over the last 2 months, he’s had increasing stress that resulted in an escalation of alcohol intake and reduced food intake.