T.R.

Eckler: my favorite acronym from this whole article is NORSE, the patients that don't respond to the initial rounds of anti-seizure medications.

I like the idea that these patients that I find really challenging are like tough old Vikings and that's why I have to really battle with them.

Sam: Hi everyone, and welcome to another episode of EMPlify I'm your host, Sam Ashoo.

Before we dive into this month's episode, I want to say thank you for joining us.

I sincerely hope that you find it to be helpful and informative for your clinical practice, and I want to remind you that you can go to ebmedicine.net where you will find our three journals, Emergency Medicine Practice, Pediatric Emergency Medicine Practice, and Evidence Based Urgent Care, and a multitude of other resources, like the EKG course, the laceration course, interactive clinical pathways, just tons of information to support your practice and help you in your patient care.

And now, let's jump into this month's episode.

Alright, ladies and gentlemen, welcome back to another episode of EMPlify.

I'm your host, Sam Ashoo, and on the other end of the microphone.

T.R.

Eckler: TR Eckler back to talk about my favorite topic, which is seizures and status epilepticus.

Sam: Nice, nice.

If you are not a regular listener, well then you should be.

But if you are not, then we actually did an article on this topic in children recently, the pediatric status epilepticus, and today we have the pleasure of the follow-up, which is emergency medicine practice September, 2025 issue on.

Status epilepticus in adults, this one, Dr.

Marquez, Dr.

Kaur, and Dr.

Lay were the authors for and it is an interesting topic.

You've seen many cases of adult status epilepticus.

T.R.

Eckler: I would tell you that this is one of my favorite things to teach to students and residents, and I find that trying to stop seizures, especially status where like the first line agents aren't working, and then trying to decide who's in non convulsive status is such a great challenging question that requires like great history, great communication with EMS, great physical exam and just a continued, you know, high level of concern and a high level to reassess the patient and see if they're improving or not.

It's just a great distillation of what doing this job well looks like.

And I think it's a great thing that involves so many different aspects of the team from, you know, nursing to the tech that does the EEGs to lab to send out labs for seizure medication levels.

It's just such a great thing that just teaches you how to work in this system and how to do the best you can for people.

Sam: Yeah, and honestly my favorite portion of this article is the International League Against Epilepsy.

Once again, I get to talk about my favorite organization.

If you're out there and you belong to the International League Against Epilepsy, I'm still waiting for my T-shirt

T.R.

Eckler: T-shirts, we want T-shirts.

Yes.

Sam: I wanna be a member of the league.

I love the name of this organization.

T.R.

Eckler: Let us make your t-shirts.

Just literally, we will start making t-shirts 'cause they're gonna be amazing.

Sam: Grant me the license.

I was happy to see that the authors did an exhaustive review of the literature, like over 75 articles, and then also pulled guidelines from the International League Against Epilepsy and the Neurocritical Care Society and the American Epilepsy Society.

And for the most part, all of these guidelines are in agreement, which is great.

Interestingly, most of the evidence comes from 2019 to now because of three major randomized controlled trials, which the authors mentioned EcLiPSE, ConSEPT, and ESETT or ESETT depending on how you pronounce that but all three of them were good randomized control studies comparing different medications for status epilepticus.

And then the authors did a good job of reminding us about the change in definition for status epilepticus.

So if you're old, and I will say like me, you remember when status epilepticus used to have the definition of 30 minutes of continuous seizing, which is utterly ridiculous.

No one ever waited that long to make that diagnosis, but that was part of the definition.

Now it is continuous seizing or seizing without return of normal mentation before the next one begins for five minutes or more in order to qualify for that diagnosis.

And I think that is a much more reasonable timeframe because I'm not fond of just sitting around watching somebody seize on and on and on.

And we we don't like that experience in the emergency department.

So a good reminder that that definition changed.

If you're a younger physician, you probably learned this in residency or even in medical school, honestly.

But if you're an older physician, you may remember that it used to be a longer period, and really the reason it is because of the morbidity or mortality, which is up to 30% for status epilepticus considered to be the most extreme form of seizures.

And that's a pretty high mortality rate, honestly.

So things to keep in mind when we talk about status epilepticus are the classification for seizures.

And this gets into some of the nuance that you probably rely on your neurology colleagues for most.

But TR you already touched on this.

You've got the convulsive and the non convulsive types.

And if they're convulsing, you can see evidence of a seizure, whether that's generalized or focal.

And if they're non convulsive, this is where it gets to be really quite difficult to make the diagnosis.

Because if they started with a convulsive seizure and now are no longer seizing, but they're altered and they haven't regained consciousness, you're wondering, eh, is there still continuing non convulsive seizure activity?

Or sometimes it can just present with altered mentation, bizarre behavior, unusual things like hallucinations and bizarre thoughts or a change in their normal personality.

These are kind of scary things because they're very easy to miss, and I think the authors did a great job of driving that point home too.

T.R.

Eckler: And I think repeated neurologic exams is really what I took away from that.

It's like there's such a wide range of these.

It's something where you're gonna medicate 'em.

Then you've gotta wait and kind of see, because yes, the seizures have stopped, but now you wanna be able to say to whoever you're kind of bringing this patient to next, what does their neuro exam look like now?

How has it changed afterwards?

What's different?

Are they back to baseline?

If they're not, what else is going on?

So I just, I liked how they, they kind of started to break this out into categories, but I find that so much of it is just you reassessing the patient and trying to see where this is going on you as it develops.

Sam: Yeah, yeah.

This is definitely somebody you're not gonna walk away from and leave the bedside for any kind of duration of time.

It's gonna take a lot of effort.

And they're usually pretty critical patients, honestly.

They're going to the ICU, they're going to neuro ICU, labor intensive.

There's a lot of resources involved in this evaluation and treatment plan.

On page four, table one does a good job of breaking down the classification for the International League Against Epilepsy's classification scheme.

I don't really we want to get into it.

It's a little complex.

And again, this is probably a great discussion with your neurologist, but it talks about things like the semiology, what it looks like when they're seizing, the etiology, if it's structural or metabolic, what the EEG findings are, and then what the age of the patient are.

Those are all the four axes that give you the classifications for what kind of seizure this was.

But for the relevant portion of the ED evaluation, it is, are they still seizing?

Do we think they're having convulsive or non convulsive status, and how do we go about addressing that?

When we talk about the etiology for seizures, there are lots of different things when it comes to the causes, acute and non-acute, and I thought this was an interesting breakdown of definitions.

So, acute etiologies would be anything within the past seven days that may have triggered the seizure.

All things like abnormalities of sugar and osmolality and electrolyte abnormalities and things like noncompliance with medication if they have a history of seizure disorder or head trauma or infections or even cerebrovascular events within the last seven days.

And then the non-acute is anything farther out from that.

And that's the most important distinction.

And interestingly, the authors did mention that, you know, almost half the cases, we don't ever figure out why this occurred even in status epilepticus.

So even in the most extreme form of seizing, despite all of the tests we can run, about 45% of the time, we're not figuring out what it is that caused this event.

T.R.

Eckler: I took away from this section just a couple of things that I thought added to my workup for these patients, which is, I wasn't thinking as much about asking about sleep patterns for these patients, but I think in this day and age, especially given how much caffeine people are taking.

Especially given the prevalence of, you know, more and more stimulants that people are using for ADHD, I think that sleep is not at an all time high in terms of how well people are sleeping.

So I think that that's something I'm gonna start at least looking more at to see.

And then I also think I wasn't looking at ammonia levels as something that that was gonna cause seizures, and I think that that's gonna be more on my workup for these patients.

I would like to know that my favorite acronym from this whole article is NORSE, the patients that don't respond to the initial rounds of anti-seizure medications, and therefore they're diagnosed with new onset refractory status epilepticus, I like the idea that these patients that I find really challenging are like tough old Vikings and that's why I have to really battle with them.

So I find that that's like a really just a, that's got a lot of layers to that acronym.

I don't like SE for status epilepticus, I just want them to commit to calling it status.

'Cause like they've got status over status migrainosus, no one's talking about migraine status.

So status is status and I think they should just stick with that

Sam: Unless you're talking to a pulmonologist, then it's asthma.

T.R.

Eckler: Status asthmaticus.

Sam: I mean, there is another one.

T.R.

Eckler: No, I still think status is seizures as much as pulm wants it.

Everyone, everyone wants it.

No, it's, it's seizures.

I'm calling it.

That's it.

Sam: It is kind of reminiscent of like acute chest syndrome being ACS.

Right?

And you're like, no ACS is taken already, I'm sorry, that's acute coronary syndrome.

You can't use that acronym.

T.R.

Eckler: Like severe asthma exacerbation, critical asthma exacerbation, however you want go for that, but status is is seizures.

That's it.

I'm calling it.

Sam: Table four on page six goes through some of the known causes of status epilepticus.

So obviously in the acute phase, if they're already on seizure medications, then if they're not taking them, that's one of the primary causes.

So, non-compliance with medications, there is the, the idiopathic, we have no idea what it is that's causing this category.

Drugs.

Lots of drug interactions can lower seizure thresholds.

So ask about recent prescribing history.

Have they started any new medications?

Are they on antibiotics?

Have they had any recent illnesses?

Because not just the medications to treat those illnesses, but the illnesses themselves can also trigger seizures.

Like you mentioned, sleep disturbances.

That can happen if you're sick.

Fever, inflammatory reactions, all of these things.

And then the medications we prescribe them for those symptoms.

Metabolic issues, structural causes, toxins, certainly, whether their exposures or intentional or unintentional, infections, and then intrinsic conditions with known epilepsy, like you mentioned, sleep deprivation being the primary one there.

And then there are some remote causes.

So these are things that would be considered maybe non-acute, even outside of seven day time period.

Things like post-traumatic, post encephalitic, post-stroke.

Anytime there's any kind of neuro injury, patients are at higher risk for seizures and status epilepticus.

Progressive etiologies like brain tumors.

Myoclonic epilepsy syndromes and dementias and neurodegenerative conditions.

Those are all things that will make you more prone to new onset seizures and status epilepticus as well.

And so it's a good differential to keep in mind when you are treating someone with status epilepticus.

And then table five also includes specific diagnoses that can cause status epilepticus, including things like intracranial hemorrhage, hypoglycemia, acute hydrocephalus, metabolic derangement of sugar and electrolytes, drug toxicities and withdrawal.

So we didn't mention that one already, but alcohol withdrawal, amphetamine, the stimulant withdrawals.

Syncope is an interesting one.

It's in the differential for status epilepticus, but it kind of is a good reminder that there are other things that can be seizure mimics, and we'll get to that in a moment.

Psychogenic, non-epileptic seizures.

Those can be very difficult differentiate from true seizures and often require things like video EEG monitoring so they can see what's going on with the patient while looking at the EEG.

T.R.

Eckler: Sometimes they're easy, Sam, sometimes they're not.

Not easy.

Sometimes the patient starts doing a fake seizure and you can yell really loud their name and they'll stop and look at you and you can say, hi, welcome back.

Sam: Yeah.

T.R.

Eckler: Doesn't seem like that was a seizure.

And then it's a good time for the family to talk about that.

But sometimes people do really convincing seizures that aren't seizures, and it's tricky.

So I don't think people should feel any sort of way that like they definitely know a seizure is psychogenic or not 'cause I think sometimes upstairs teams will be kind of questioning of that, but it is not always easy to tell.

But sometimes you can.

Sam: Yeah.

And that, you know, the psychogenic non-epileptic seizures are not necessarily synonymous with malingering.

So you know the intent is not necessarily there.

It's not that the patient is trying to fool you into the fact that they're having a seizure.

It's just that they have this manifestation that looks like a seizure, and we're trying to determine the intent.

And so that's where that name comes from, that it's psychogenic.

It's not necessarily epileptiform or abnormal electrical activity of the brain.

But yeah, you're right.

And the authors, we'll get into this in a second in the physical exam section, they did talk about some things that are typical of a true seizure and typical of a non-epileptic seizure.

Movement disorders, dyskinesias, severe Parkinson's disease, and Guillain-Barré syndrome, all things that should stay in your differential diagnosis when you're thinking about status epilepticus because they can increase tone and kind of present with status epilepticus mimics.

So things to keep in mind.

The authors did do a good job, I think, of addressing syncope.

So, syncope, the loss of consciousness, often comes with some shaking and some, you know, seizure-like activity, and then the person regains consciousness, and then there's no continued altered mental status.

As soon as they wake up, they're better.

And that tells you, okay, this wasn't a true seizure.

This was just bad perfusion to the brain.

We weren't getting enough blood for a few seconds, hopefully.

The description of the tonic-clonic, jerking, tongue biting, mouth clenched, eyes deviated.

Those are the kinds of things you're gonna elicit from history from a bystander that will kind of send you down the, the seizure route instead of a mimic like syncope.

In the pre-hospital setting there are s ome key things that the authors pointed out that our pre-hospital colleagues should be doing and would be helpful.

Number one is always airway, breathing, and circulation.

Number two is pharmacologic treatment to abort the seizure.

So this kind of seems like a no-brainer, but we're not just gonna wait for the seizure to end.

We're gonna give something to terminate the seizure and hopefully prevent a second one.

Number three is preventing additional trauma to the seizing patient.

So this can happen when someone is seizing and falls off a couch or someone is seizing and falls out of a chair and smacks their head on the glass table on the way down on the floor.

Or if they're in the EMS stretcher and they haven't been completely secured and they start to have another seizure again, they fall fall off the stretcher while you're moving them out to the ambulance.

You know, those things do happen and you just gotta be super careful.

If they've had one seizure, they may have another one.

So you gotta anticipate that.

And lastly, the fourth item was gathering available medical history from the scene, including medications, pill bottles, and signs of drug use, right?

So in addition to getting the history from any people that are around, you're gonna wanna look for all of those items because they can clue you into what may be the cause, and that's very helpful information to us in the ED.

T.R.

Eckler: I would add family contact information to that.

'cause I always wanna try to get some kind of story from family.

Like, Hey, is the patient really taking their medications?

What seizure meds have they responded well to in the past, if you know which ones did they not respond well to?

I find that directs a lot of my therapy more often than not.

Sam: Yep.

I thought also the authors did a good job reminding us that because of suppression of the gag reflex during status epilepticus, the patient should be placed in that left lateral decubitus position.

This can be really hard if they're actively seizing.

But something to think about, even if it's a little bit of a tilt and shove a few pillows underneath them and that it's not recommended to stick anything in their mouth.

Right?

You don't wanna put in a bite block or try and force open a clenched jaw, you will lose fingers that way if you are a paramedic or an EMT or even a first responder of any sort.

So don't go putting anything into a clenched mouth, just turn 'em on their side and a little supportive care.

If you do have to give them something because of hypoxia or their respiratory drive is not very good, you can use a nasal pharyngeal airway, you know, that's a, that's a good device.

Goes in the nose and goes all the way to the back of the pharynx, gets that tongue outta the way and helps with hypoxia sometimes, and then a little supplemental oxygen.

And then you follow your ACLS protocols.

So obviously if all of that doesn't work and you have to medicate and intubate, that's what you gotta do.

So you get aggressive and you get aggressive quickly.

Point of care blood sugar is very, very critical in this scenario because that can be an easily fixable cause for status epilepticus that you don't wanna miss.

T.R.

Eckler: You lose points for intubating hypoglycemic people.

That's always a negative one point.

Sam: Yeah.

And then IV access.

This is very helpful, especially if you're gonna go down the ACLS protocol pathway.

But you know, if you are unable to get it, there are IM intranasal options.

IO.

There's all kinds of other methods for access that are available to you pre-hospital.

So you guys are the experts when it comes to that and staying adept at using all of those tools and knowing which medications, especially like midazolam, which can be given just about in any way you could possibly get it into the body is very effective in terminating seizures.

T.R.

Eckler: I am falling out of love with intranasal medications 'cause I find that often I don't get all of the medicine in that I want to.

And I think that they made a great case in this article for the efficacy based on research and trials of intramuscular midazolam, especially in the pre-hospital setting, where before you're even worried about getting the IV, if they're seizing you check the sugar, bang, give 'em some midazolam because then you're gonna stop them.

And I think the majority of cases it was even more effective, I think, than IV lorazepam.

So I took that as like good drug, short acting.

I think intramuscular is a good, safe way to give that drug 'cause I think it comes on in a nice fashion that doesn't usually gimme respiratory depression.

And I think that that was my big takeaway from pre-hospital or from if they get to the ER and I don't have an IV, that's where I'm gonna go first.

Sam: Yeah.

Yeah.

I mean, if you have never tried to put an IV in someone in the back of a truck, imagine them now seizing while you're doing that.

It's just, it seems impossible.

Somehow our pre-hospital colleagues can still get them which is amazing and a testament to their skill, honestly.

But yes, by all means, give them the IM midazolam and then go after the IV when they've stopped seizing.

It'll just make it that much easier.

And hopefully that's already in your pre-hospital protocols for treating status epilepticus or a seizure.

So yes, midazolam, check the blood glucose, get the history, bring them on over to the ED.

And the dosing is written there in the article for adult and pediatric dosing for IM Midazolam.

It is perfectly safe and the authors did note it terminates seizures 73% of the time versus IV lorazepam, which was 63% of the time.

And you know, it seems like that's only a 10% change, but that was statistically significant.

So it's worthwhile.

And if it's gonna delay stopping the seizure, just give it to 'em IM And then try and get your IV.

T.R.

Eckler: I took that away from this article too, in the, the theory and some of the pathophys they talked about, that the longer you wait to give medication, the more likely it is to not be successful in terminating a seizure in a patient with status.

And I think that made me more inclined to get benzo into the person as fast as as I can, and I think intramuscular Midazolam seems like that's the way.

Sam: That was a great discussion that we didn't really touch on.

But the pathophysiology there is that the longer that the brain is seizing, the more changes in biochemistry you get, the receptors that are on the outside of the cells are downregulated.

Those GABA receptors are starting to go away.

And so the medication, the benzos that we give that are supposed to attach to those receptors, just have less targets.

So the longer you wait, the more ineffective those medications get and the more likely you are to head down the intubation and, you know, initiate a coma route, which is the ultimate thing that we're trying to avoid, but is sometimes necessary in these cases.

Okay.

When they get to the emergency department, the history we touched on is very, very important.

So assuming you have the time and there's family available or some other resource, you want to ask about all of these things we just mentioned, toxin exposure, recent trauma, recent hospitalizations for stroke.

Do they have a brain tumor?

Is this a known problem?

Is it a new problem?

All of these questions you're gonna ask, and hopefully if they come by ambulance, EMS is gonna provide you with the answers to most of these.

And then when we get to the physical exam portion, this is where now you're starting to do those serial exams again and again and again to look for changes over time as they're seizing.

You're gonna note what kind of seizure.

It's very helpful, I think, for our neurology colleagues to note the laterality of the seizure activity.

So if it's not just a completely generalized seizure and it's focal, making a note of yes, it was their left arm and their left leg that was hypertonic and shaking and had some tonic-clonic activity.

But their right side seemed completely flacid and their eyes were deviated, you know, to the left or to the right, those are kind of important things to note because they can become clues that you need to then chase something down with imaging.

And we'll talk about that in just a second.

T.R.

Eckler: I would add that I think it's important to ask family too, is this what their seizures usually look like or is this different?

Because if it's different, then I think that heightens me a little more that maybe there's something else going on.

And then again, I, I think that this is the time where you ask family, you know, while you're examining the patient, what medicines they're on and what medicines they've responded well to or poorly in the past.

I had a family recently that really asked me not to give Keppra because they said the patient has a lot of psychiatric issues coming off of Keppra afterwards, so I ended up going with fosphenytoin instead of Keppra after talking with neurology, because it seemed like that was probably the best thing for the patient, even though the loading time on  fosphenytoin is significantly slower.

Sam: Yeah.

And you can also ask about things like, you know, have they had multiple seizures like this in the past?

And sometimes I find that to be kind of something that just reduces my anxiety when the, parent says, oh yeah, you know, usually they have these stacked 5, 6, 7 in a row over the course of a few hours, and I go okay.

Okay.

So now I know what we're dealing with, you know, oh, they're on five different anti-epileptics and we're gonna run the gamut of the meds with them, but it's been difficult to control.

That's very, very helpful information to elicit for sure.

In the physical exam section also, you wanna note the response to any medications you've given.

You know, sometimes we rely on our nursing colleagues.

We say, okay, go give them 10 of Midazolam right now and then I'll be right back.

And, you know, if the nurse comes up and says, Hey, great news, they've stopped seizing, I have personally had these scenarios where it is thought that they stopped seizing.

And then I walk in and I open their eyes and I go, eh, their eyes are still deviated.

They're not as tense, but I'm gonna pick up their arms.

And there's still some increased tone in these extremities, and this seizure hasn't actually stopped.

They're just not overtly shaking.

So the subtleties matter when it comes to this examination.

You don't have to pull out your reflex hammer, but you do have to go and pick up the arm or the leg and check the tone, look at the eyes and most of the time, I think you'll get your answer pretty quickly.

T.R.

Eckler: And I think like to your point too, I think this is something where we're always kind of really highly suspicious and the data backs this up.

Like I think 50% of patients that aren't coming back to normal, are still in non convulsive status.

So we're chasing the right fear here, like this is not something where like, you know, one in a hundred or one in a thousand.

These patients are still having some signs of seizures.

So like your desire to escalate and keep going and push further is rightly, I think, justified.

Sam: Yeah.

Yeah, great point.

Not a zebra.

It definitely occurs and it occurs a lot.

There is a good table on page nine about laboratory testing.

So once you've gotten past the physical exam and we're jumping into diagnostics, everybody's getting a very broad set of labs, which includes the metabolic profile but a finger stick glucose, if it wasn't already done by EMS or they didn't come in by EMS, that's something you're gonna do first, right away.

A complete blood cell count looking for leukocytosis and signs of infection.

Typically seizures can even cause transient leukocytosis.

So just an elevated white blood cell count by itself doesn't mean it's infectious, but something to keep in mind.

The comprehensive metabolic profile, which most of time does not include your ammonia, so if you're gonna get some liver functions, adding the ammonia is helpful.

Sometimes the ammonia is just high because of the anti-epileptics they're taking too.

'Cause that can affect liver function depending on which agent they're taking.

So

T.R.

Eckler: Also doesn't give you a magnesium level, so you gotta add a magnesium on top if, if you're chasing that.

Sam: Yeah, for sure.

Urine is helpful because it can be a source for infection, but also if you're doing urine toxicity screens instead of serum toxicity screens, you need to know if they have those metabolites in their urine.

Again, not a hundred percent.

There are a lot of things that'll give you false positives, so make sure you, you're aware of that.

Serum levels for medications and for exposures, so toxicity, things like Tylenol and alcohol and,

T.R.

Eckler: Lithium.

Sam: Lithium.

Yes.

Yes, absolutely.

T.R.

Eckler: Great one.

I think in this day and age too, there's such a challenge of following up with primary care and neurology.

I've started sending more and more seizure drug levels, and I just had a patient bounce back who was a seizure patient who wasn't able to follow up, still felt like she was gonna have a seizure, felt like she had prodromal stuff, and I got to see that her Keppra level was therapeutic, but she was still kind of having a sense of breakthrough seizures.

So I got to kind of adjust.

I got to kind of help her get better, closer follow up, but I felt like it answered the question of her compliance, so I think it's gonna help her get on a second line agent if she kinda continues to have symptoms or adjust her medication where it is now.

Sam: I like that.

I like that a lot.

Yeah, it kind of takes a non-compliance out of the picture and really kinda lends validity to the fact that this person's actually trying and has been compliant.

That's good.

T.R.

Eckler: They're send out tests and I think a lot of times we tend to brush off send off tests in the ER, but I think that this is gonna help these patients get better care when they kind of continue to follow up even if they're just coming back to the ER 'cause you can make better decisions if you have better data.

Sam: Excellent point.

Lactate levels, prolactin levels.

Now these are sometimes measured 10 to 20 minutes after a seizure and have a sensitivity and a specificity about 53% and 93%.

So it's not perfect.

Just because they don't have an elevated prolactin level doesn't mean they weren't having a legitimate seizure.

But if they do, again, it can help you in that differential, especially if you're considering something like the psychogenic, non-epileptic variety.

Creatinine kinase because of rhabdo, which can happen, especially with prolonged seizures.

And since we're talking about status epilepticus, if they're continually seizing for a long period of time, something you need to be aware of.

They can develop the rhabdomyolysis and acute kidney injury.

Troponin is interesting actually, and it's not one that I think about initially in my laboratory battery for status epilepticus, but it does drive home the point that if there is concern that they had syncope first and that they maybe had multiple seizures instead of the continuous seizure, maybe this is cardiogenic, maybe they're having some kind of arrhythmia each time that we see a seizure on the outside.

And the only point there was that if the troponin's elevated, you need to repeat it and maybe consider further cardiac testing.

So it's a good point to drive home.

Cultures if they're febrile, and then pregnancy test, if they're within the age range.

That is a critical test to obtain because the treatment pathway takes a giant left turn if the patient is pregnant.

T.R.

Eckler: And I think that sometimes blood tests take a long time.

So this is my annual reminder that most rapid urine cartridges in the United States are dual certified for blood and urine.

So you can just take whole blood, put it on that cartridge, and it will give you an answer as to whether the patient is pregnant in just a couple of minutes.

So if you've got questions and you're really worried, just have the lab send you one of those cartridges and you can know right away.

Sam: There you go.

May have to do it yourself if the lab tech is not allowed to do it, but doesn't mean you can't do it.

Alright, let's talk about imaging.

So you know, status epilepticus, I think most people are going to get some kind of imaging especially if they have an unusual change and this is not their norm.

It's hard to believe that it will be the norm for anybody.

But the point driven, I think, by the American College of Emergency Physicians is that most of these patients are gonna get a CT scan without contrast.

That's what we have available in our department.

And then at some point they'll go on to get MRI imaging, you know, after neurology's gotten involved, to look for some of the more subtle things that can cause abnormalities.

But just keep in mind, the non-contrast CT doesn't rule out everything bad.

So you may have to go chase it with other things especially if you're looking for increased intracranial pressure.

Now if they're not having the generalized tonic-clonic seizure, this is a good opportunity to pull out your ultrasound and do a quick ocular ultrasound and look at their optic disc and get that quick optic nerve measurement, and that can give you a, measurement that can suggest increased intracranial pressure as an etiology and is a quick, rapid bedside test to do.

So, something to think about.

And if you're worried about other etiologies you can then get things like CT venograms, MR venograms in patients who are hypercoagulable or pregnant or have a persistent headache, or if you do the ultrasound and you see papilledema.

So all of those things are possibilities.

But by far, the initial study that we're all obtaining is just a non-contrast CT of the brain.

Then moving on to something that may be necessary.

And that's the lumbar puncture.

So if you have an abnormal ultrasound finding and you are considering increased intracranial pressure, then that is one way to measure it directly.

Obviously, again, very difficult to do while they're still seizing.

So this is kind of after you've either terminated the seizure or intubated them and initiated a coma, and then now you're able to have them be still for this procedure.

It's also very helpful to look for infections.

It's helpful to look for pleocytosis, evidence for increased protein and other things that can help you down the differential diagnosis for causes for status epilepticus.

So it's not just for pressure and not just for infection.

T.R.

Eckler: Yeah, I think more autoimmune, more neoplastic cases like, I think that's more and more of what we're starting to see is that these cases that we can't find a cause, the more we get into them, the more finding it's those kinds of things.

And I think the more you can get an LP on those patients, and the earlier you can get it, I think the more yield you're gonna get and the faster the inpatient team's gonna get to the answer.

Sam: And you don't even have to know what tests you need to order.

Just get the fluid and have it sitting in the lab.

You're gonna look for infection, and then they'll add on a bunch of you know, antibodies and things that they're looking for considering the differential

T.R.

Eckler: Fancy upstairs tests is what I call 'em.

Sam: Nice.

And then there's the EEG.

So again, it's very, very helpful to get neurology involved early.

If you have an EEG tech and the ability to get these EEGs in the emergency department, it's very helpful to get them contemporaneously with all the other stuff.

It's exceedingly helpful in the differential diagnosis and to determine if they're still seizing.

You know, the ESSEP trial that the authors mentioned was a randomized controlled trial, 475 patients in 58 different hospitals.

48%, so only half of the patients, actually had altered consciousness following status epilepticus and continued to have non convulsive seizures on EEG.

So, half of those still seizing, but without any external signs of continued seizure, like you mentioned before.

And so this can be particularly challenging and this is a great tool for trying to detect that early.

T.R.

Eckler: This technology is just advancing.

I feel like we're gonna see more and more interesting ways to like do seizure monitoring on people as it just gets more micro and easier to use, you know?

Sam: Yeah, and typically the EEG testing we're doing in the ED is spot testing, or it's kinda a one time 30 to 60 minutes and then it's done, but these patients really need continuous EEG monitoring, especially if they're intubated and going to the ICU.

And so that can be done with traditional EEG equipment.

It can be done with video.

It can be done with some of the newer AI technology that is also monitoring brainwaves and then alarming.

So lots of different options.

And there are even some smaller products now for emergency departments that don't have EEG techs available where you can do a spot EEG with just two or three electrodes and get a quick reading.

They're not as accurate.

They do have a lot of false positives, so, you know, understanding all of that, the technology's getting better.

But hopefully if you don't have EEG where you are, you've got one of these devices you can at least get an initial reading from.

All right, let's talk about treatment.

So there is, we touched on this already with Midazolam, but there's a great table on page 10, medications for status epilepticus, which gives you first line, second line, and third line agents.

The first line agents are always going to be the benzodiazepines.

Rapid onset have very good evidence for terminating seizures even in status epilepticus.

And that's what you want to give first.

You do have IV and IM available to you with Lorazepam and midazolam.

There are some parents with children who seize at home who are still using the rectal diazepam as well.

But Midazolam and Lorazepam both have actually better efficacy.

So if you have an IV or can give it IM, that's still the preferred route.

T.R.

Eckler: There's a new product called Valtoco that's basically nasal Valium, and I find that that's replacing a lot of the rectal Valium that's out there now.

I also would note that I think that drug shortages are really affecting this.

Sam: Mm.

T.R.

Eckler: Right now we don't have any access to Lorazepam.

So despite it being the first line agent, it's not something that we have readily available in the intravenous form in our hospital.

So you've gotta be ready to adjust to hospital supplies, drug shortages.

So I think that's why this table is so valuable is because you need to be ready to use what agents you have and then be ready to escalate, not just to like one of the things in the next group, but any of the things that are available, depending on what you have and what the patient actually responds to in the past.

Sam: Yeah.

Yeah.

And on this topic, it's also important to make sure you're giving the right dose based on the person's weight.

So, you know, adult doses of lorazepam are maximum four milligrams per dose, but it's 0.1 milligrams per kilogram.

If you're dosing midazolam especially if you're giving it IM in an adult, it's 0.2 milligrams per kilogram with a maximum of 10 milligrams.

So underdosing is a frequent problem that results in recurrent seizures and in continued status epilepticus.

So don't be afraid to give the full dose and if they have somnolence and respiratory failure, you deal with all that.

You have the tools to work with all of that.

But priority number one is terminate the seizure and make sure you're giving the right dose.

T.R.

Eckler: Stopping a seizure, but arriving in intubation is a win so long as their glucose is normal.

That's my feeling about status patients like this.

Sam: That's perfect.

That is a perfect summary.

Second line agents include things like levetiracetam, valproate sodium, fosphenytoin, phenobarbital, and lacosamide.

So all of these medications are in the second line therapy arena, and you're gonna give your benzos and you're probably gonna give your benzos again before you reach for one of these things.

So it's like, give a dose of benzos, wait a minute or two, give another dose of benzos, and then reach for one of these agents.

And this is where it becomes helpful to know what they're taking at home, because it may or may not be effective.

If they haven't been on it for a while, you may have to give a loading dose.

Levetiracetam has always been my favorite just because of the ease of dosing and the loading and I think our neurology colleagues quickly became fans of it as well because of its ability to be loaded in people with renal failure and with all kinds of other metabolic issues.

It's like just give the loading dose and we'll worry about the next one later.

But there are others.

So keep in mind there are four others to choose from on the list besides levetiracetam.

And like you mentioned before, just know what you have in your pyxis, know what you have in your pharmacy, and consider how long it's gonna take to give it as well.

T.R.

Eckler: Levetiracetam for a hundred kilogram person, you can give it in about nine minutes, if you're kind of going at the max rate of about five mgs per kilo per minute, but then if you're looking at the other drugs on there, it's gonna take significantly longer.

And I think that then adjusts, if you know you start that load, but the patient starts seizing, you need to be ready to move to your third line agents.

You know, maybe think about a dose of ketamine, or you're going to full on intubation and the other drugs.

But I think you need to know how long it's gonna take to get that medicine into the patient, and then be ready with how your plan responds according to what you've got available and what you're gonna use.

Sam: And keep in mind, the maximum dose is probably way higher than anything you've ever given.

You know, levetiracetam's a great one, max dose four and a half grams.

Can't say I've ever dosed anybody with that much but your neurology colleague may ask you to do so for somebody headed to the ICU with continued non convulsive status on EEG, you're gonna keep pushing that higher and higher.

So just be aware that the max dose is much higher than the routine dose we give.

All right.

And then third line agents.

So this is the person who's now about to be intubated and put on a ventilator.

And we're looking for continuous infusions, right?

So Midazolam still in this list, right, has shown good efficacy.

There is good published data for midazolam versus propofol, and they're about equal for continuous infusion.

Now, whether or not you have midazolam available and that much available is another question, but just know that can be a method for controlling continuous seizures.

Propofol certainly always one of my favorites, but comes with the propofol infusion syndrome as a possible side effects and lots of derangements and increased morbidity and mortality.

So uh, your colleagues in the ICU may rapidly change them to something else, and that's okay.

Pentobarbital is something I have personally never given, but may be available in your pharmacy.

Thiopental is also something I've never had to give, but may be available in your pharmacy.

And lastly, ketamine.

So ketamine, interestingly, a little asterisk there, was recommended by the authors as something you might try before you reach for a continuous infusion and intubate somebody as a single dose because there is a growing number of case reports of people who have terminated seizures with a dose of ketamine.

Not as a continuous infusion, but just a dose of ketamine before progressing to intubation.

And you might be able to keep somebody off a ventilator.

T.R.

Eckler: I think especially as you're getting ready to start infusion, it takes time.

I think you've got that moment there where if they're still seizing or showing you signs of non convulsive status where they're not coming around.

I think that there's room for that dose of ketamine, while you're getting set up for everything else.

I also think to your point, I reach more for midazolam in children and I reach more for propofol in adults.

But I think it depends on kind of the patient's history, what their blood pressure looks like.

I think there's a lot of factors that go into this and I think that all of those things are now always part of my evolving approach to these patients.

Sam: And if you're wondering, you know, about the clinical efficacy for each of these medications, especially like second and third line agents, the authors did a good job of saying, yes, there is published data for all of these and the efficacy is about the same.

So you know, levetiracetam doesn't work necessarily any better than fosphenytoin, and doesn't necessarily work any better than valproate and propofol doesn't necessarily work any better than midazolam.

It's more what you have and what you can get quickly.

Okay.

And then these are the patients who are going to the ICU and considered super refractory status epilepticus.

So I think that's gonna be the highest category where they just continue to seize no matter what you do.

And I think that at this point, if you haven't already gotten your neurology colleagues involved, it's going to be whatever agents they prefer on top of whatever continuous infusion you've provided.

T.R.

Eckler: To the final boss of the NORSE seizure battle game that you're playing.

This is like the tough boss that you've gotta use all your weapons on.

Sam: That's right.

The big boss at the end of the video game

T.R.

Eckler: The big boss at the end.

Sam: And then some special populations, right?

So there are going to be some cases which are handled differently.

Pregnancy is certainly one of them.

So if your patient is pregnant and presenting with continuous seizures or status epilepticus, then eclampsia needs to be at the top of the list, and the first agent you're reaching for is magnesium.

And that is a giant whopping dose of four to six grams IV over 15 to 20 minutes.

So it's a very rapid infusion of magnesium, followed by a continuous infusion of one to two grams per hour.

And then you're getting your OB colleagues involved and kind of discussing maybe delivering of the baby at this point.

So that's a very, very different pathway that you need to identify immediately before you are giving other substances.

Now you can still give lorazepam, you can still give fosphenytoin, you can still give levetiracetam.

Some of them don't have the greatest side effect profile in pregnancy.

But if they get the mag and they continue to seize , you're not out of medication treatment at that point, you can still give these other agents in consultation with your neurologist and your OB because the longer the mother is seizing, the longer her brain is at risk and the longer the fetus is at risk.

So you're saving both lives in this scenario.

T.R.

Eckler: You did put a little caution on fosphenytoin and valproic acid .

So it seems like levetiracetam, which you're so much better at saying than I am, is more of the kind of recommended third line after your, magnesium and your benzos.

But as I think you said, I think you give those three things while you're punching the number for OBGYN and getting them to the bedside.

'Cause delivery is really the thing that's gonna save this duo here.

Sam: Yeah.

And you know, in pregnancy, it's not just eclampsia, but it's things like posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome and cortical venous thrombosis, all of these things can cause seizures in the pregnant patient.

So the differential is different and it is treated differently in most cases.

Just don't forget the mag and the mag and the mag because that's the treatment of choice.

There is substance induced status epilepticus, so somewhere between nine and 10% of status epilepticus cases are substance induced.

And these are things like antidepressants, stimulants, antihistamines, tramadol, isoniazid, and they can have some specific therapies.

So if you know that they're using isoniazid and they're toxic from it, then pyridoxine is the treatment of choice.

Phenytoin interestingly, not as highly recommended in drug-induced status epilepticus.

Doesn't tend to do as well.

But your other choices are pretty good.

And your, you know, your first drug?

Well, my first drug levetiracetam is the one that seems to work okay in these patients.

So just know that there's a significant number of patients and drug toxicity is definitely in the differential.

T.R.

Eckler: Your catch for the isoniazid patient is a tuberculosis patient that tried to kill themselves and took too much of their tuberculosis medicine.

And I think the classic teaching on this is that if you need B6 to try to stop these people's seizures, you need all the B6 in your hospital and all the B6 in a bunch of surrounding hospitals.

So once you've made this diagnosis, it's also one where you need to make that next step to talk to your pharmacy and say, Hey, we're gonna need a lot of B6.

You know, this is what I've got.

Figure out how much we're gonna need and then figure out where we're gonna get it from.

And let me know.

Sam: Yeah, and you're gonna need some isolation.

T.R.

Eckler: Well, it depends.

If it's not really active TB, you just, you can just fix the seizures.

But, we'll, we'll get to that part.

I'm sure they came in with full PPE.

Well contained.

Everything taken care of.

Sam: And then there was a great section there on pediatric patients, which actually I'm not going to dive into, but I will encourage you to go back a couple of months on this podcast and listen to the episode we did on pediatric status epilepticus.

It is a little different but overall I think the management points were, were very, very similar.

You stop the seizure, stop it early and make sure you're aware of what medications you have and what exposures the patient has had.

T.R.

Eckler: Here's my annual plug for the wonderful PD stat app, so that if you have a kid that's sick with anything, you can use the PD stat app to base your doses for their medications on their Broselow Tape, or their age or their weight, whatever you've got, the most accurate measurement you have for their age and size.

Then that will give you every drug you need and everything you need to resuscitate them right there.

It makes the cognitive load decrease dramatically so you can just focus on getting that little bugger healthy and back to normal again.

Sam: Yeah.

Before we end, I wanna put in a quick plug for the risk management pitfall section in every single one of these issues.

They're fantastic.

We're gonna go through a couple today for the status epilepticus.

The first one, the patient isn't having any abnormal movements, so he's not seizing anymore.

I think we drove that point home pretty well.

That non convulsive status epilepticus is a thing and you should be very suspicious.

T.R.

Eckler: Turn.

Turn that on its head a little bit.

If the patient isn't moving, you should be a little worried.

They should start moving.

Sam: Yeah,

T.R.

Eckler: Movement, good.

Too much movement, bad.

No movement, also bad.

Sam: Also bad.

That's right, that's right.

There is a sweet spot somewhere in the middle

T.R.

Eckler: Yes.

Sam: Number two, we gave two milligrams of lorazepam so the seizures should stop.

The point here being that it's not a standard dose, it's a weight-based dose, and you wanna give the correct amount based on the patient's weight, which could be up to four milligrams.

And repeat that once with a maximum dose of eight milligrams before you go on to your next agent.

So if you gave them two and it didn't work and you gave them two more, you're only halfway there before you should be giving anything else.

So make sure you get the right amount.

The point of care EEG showed no seizures, so we didn't need formal EEG monitoring, and that's just a reminder that this particular product is good to have but doesn't yet have the sensitivity and specificity needed to completely exclude continued seizures.

So you still need a dedicated EEG for the non convulsive cases.

T.R.

Eckler: So you've just given them a ton of drugs to tamp down their ability to have a seizure.

So you need to then watch them as those drugs fade away to see what develops.

And that's what they're getting admitted for.

Sam: Yep.

And if you can't do that at your facility, that's okay.

You gotta send them somewhere where they can Right.

Transfer them.

The patient has a history of epilepsy, so the seizure must be due to non-adherence.

No further workup is required.

I think your example of the levetiracetam level you did on that patient, it was a, was a great one, right?

So she was compliant and yet still having seizures.

It happens.

Something to keep in mind.

T.R.

Eckler: I had an alcoholic once in rural Colorado that was known to go into withdrawal seizures, and I was used to giving him a dose or two and he would stop and we'd be fine.

And I, one time I just couldn't get him to stop and I had to intubate him and I felt like I just had not managed it correctly.

And then I took him to CT and he had a giant head bleed.

Sam: Hmm.

T.R.

Eckler: That's, it's one of those things where, if the patient has a history of seizures and you're not getting them to come around , it's 'cause there's something else there.

So keep working 'em up, keep working the problem.

Sam: Great case.

Great case.

The patient has renal failure, so I should reduce the loading dose of levetiracetam.

Again, that loading dose is the same upfront.

Now your follow-up doses may be different and the schedule may be different, but the load is the same.

We successfully treated the seizures so the patient does not need a higher level of care.

Interesting point here that if a patient is no longer seizing and they don't meet the critical care unit requirements you still need admission to an inpatient neurology service or a place where that's available to get the rest of the workup.

And so terminating the seizures, great.

That gets you most of the way there, but then you gotta figure out why it happened.

T.R.

Eckler: Again, these are patients with status epilepticus.

It's not just patients with just seizures that come back to baseline.

The patients with status who aren't returning their baseline, who've had multiple seizures required multiple medications.

There needs to be a higher threshold for these patients than just your usual had one seizure and now is normal patient.

Sam: The patient's seizures stopped after I administered benzodiazepines, so they don't need any more medication.

And the point here being that great you have terminated their seizure.

But that medication is very temporary, very short acting.

And they need one of those second line agents to provide consistent control and not allow any more breakthrough seizures.

So just terminating it is not enough.

And lastly, the patient saturations are in the low nineties, so I'll give a lower dose of benzodiazepines to protect the airway.

And this really just drives the point of you're gonna stop the seizure first and deal with the respiratory depression some other way by controlling the airway.

Don't worry about respiratory suppression because if it happens, you're gonna need to intubate this patient anyway.

Stop the seizure, don't let it continue.

T.R.

Eckler: And their receptors are downregulated, so you need more benzo to break through that.

So I liked their argument.

I thought it was a good one.

Sam: Yep.

More benzos, more quickly, as fast as you can.

And as always, the last page has a clinical pathway.

So it includes the medications, the dosing, the first, the second line, the third line, when to give 'em, do the seizures persist, how to give 'em, et cetera.

It's a great little pathway to have.

So if you don't want just a table of meds and you want a step-by-step progression, it's a great one to have in your back pocket for how to treat these patients.

They are very anxiety provoking patients because you want to stop the seizure and you don't kind of get to relax and pause until you stopped the overt seizure.

So having a clinical pathway in your back pocket is exceptionally helpful.

And offloads some of that brain activity of your own.

All right, ladies and gentlemen, that's it for the September 2025 issue of Emergency Medicine Practice on status epilepticus in adult patients.

Thanks again to the authors.

Fantastic article, great summaries, great tables, and an excellent pathway.

And as always, I'm Sam Ashoo.

T.R.

Eckler: TR Eckler, good luck with those super Vikings.

Sam: The Norse.

The Norse.

My nemesis.

All right, thanks everybody.

See you next time.

And that's a wrap for this month's episode.

I hope you found it educational and informative.

Don't forget to go to ebmedicine.net to read the article and claim your CME.

And of course, check out all three of the journals and the multitude of resources available to you, both for emergency medicine, pediatric emergency medicine, and evidence based urgent care.

Until next time, everyone be safe.