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Seizures In The ICU
3 Plays6 years ago
In this episode, we discuss seizures in the ICU. We cover a broad range of topics related to the initial management of seizures, status epilepticus, and EEG monitoring in post-anoxic brain damage. Our guest is Dr. Thomas Bleck. Dr. Bleck is the professor of neurological sciences, neurosurgery, internal medicine and anesthesiology at Rush University Medical Center, where he is a neurointensivist and the director of clinical neurophysiology.
Additional Resources:
Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society: http://www2.soundphysicians.com/l/403342/2018-06-27/cxz5ng/403342/102465/Evidence_Based_Guideline_Treatment_of_Convulsive_Status_Epilepticus_in_Children_an.pdf
Guidelines for the Evaluation and Management of Status Epilepticus: http://www2.soundphysicians.com/l/403342/2018-06-27/cxz5nb/403342/102461/Guidelines_for_the_evaluation_and_management_of_status_epilepticus..pdf
Clinical classification of post anoxic myoclonic status: http://www2.soundphysicians.com/l/403342/2018-06-27/cxz5nd/403342/102463/Clinical_classification_of_post_anoxic_myoclonic_status.pdf
Books Mentioned in This Episode:
Tinker, Tailor, Soldier, Spy: A George Smiley Novel: https://www.amazon.com/Tinker-Tailor-Soldier-Spy-George-ebook/dp/B004RKXNDU/ref=sr_1_1?ie=UTF8&qid=1530020470&sr=8-1&keywords=tinker+soldier+le+carre
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Transcript
Introduction & Guest Introduction
00:00:09
Speaker
Welcome to Critical Matters, a sound critical care podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:17
Speaker
And now your host, Dr. Sergio Zanotti.
00:00:22
Speaker
Welcome to another episode of Critical Matters.
00:00:25
Speaker
Today we will discuss seizures in the ICU.
00:00:28
Speaker
It's a pleasure and an honor to have as our guest Dr. Thomas Bleck.
00:00:32
Speaker
Dr. Bleck is professor of neurological sciences, neurosurgery, internal medicine, and anesthesiology at Rush University Medical Center, where he's also a practicing neurointensivist and director of the clinical neurophysiology.
00:00:45
Speaker
Dr. Bleck is board certified in internal medicine with subspecialty certification in critical care medicine,
00:00:51
Speaker
also certified in neurology with subspecialty certifications in vascular neurology and epilepsy, clinical neurophysiology, and in neurocritical care.
00:01:00
Speaker
Dr. Bleck has been elected as a Master of Critical Care Medicine by the American College of Critical Care Medicine and Society of Critical Care Medicine and has received numerous awards for his contributions to critical care and to neurocritical care.
00:01:13
Speaker
He's one of the founding fathers of neurocritical care as a specialty,
00:01:18
Speaker
and is an ex-official member of the board of directors of the Neurocritical Care Society, of which he was the founding president.
00:01:26
Speaker
It's truly a pleasure to have him today to discuss seizures.
Initial Seizure Response
00:01:29
Speaker
Tom, welcome to Critical Matters.
00:01:32
Speaker
Thank you.
00:01:34
Speaker
So I think that a good place to start would be, I tend to notice that when a patient has a seizure in the hospital, where it's in the emergency department, on the floors, or even in the ICU,
00:01:48
Speaker
And perhaps this doesn't happen in a neuro ICU, but at least in general ICUs, it seems that nobody really knows what to do.
00:01:54
Speaker
It's one of these very traumatic events, both for families, but also, I think, for the staff.
00:01:58
Speaker
And it always catches my attention that nobody really seems how to deal with these seizures.
00:02:05
Speaker
Could you tell us, to begin with, Tom, what should we do when somebody sees it in front of us?
Seizure Treatment Protocols
00:02:12
Speaker
I think the first thing to remember is that almost all seizures are going to end spontaneously.
00:02:19
Speaker
So there is no need to immediately rush in with some sort of therapy.
00:02:24
Speaker
Rather, observe how the seizure starts and mostly try to protect the patient from any harm.
00:02:31
Speaker
You don't want the patient, for example, to get smothered by the pillow or the sheets, which still happens from time to time.
00:02:39
Speaker
In the hospital, most of the things that are harmful out in the community won't be present, like the ability to
00:02:46
Speaker
bump into a radiator or put your hand on an open glass flame.
00:02:50
Speaker
But people can still be injured in the hospital, especially if they're seizing down on the floor where they can collide with objects.
00:02:59
Speaker
So when the seizure is over, which in the vast majority will end spontaneously, turn the patient to the side in the recovery position to try to prevent them from aspirating.
00:03:11
Speaker
Of course, if they're already intubated, that's not an issue.
00:03:15
Speaker
Secretions in the mouth can be a problem, but don't stick anything in the mouth except perhaps to separate the teeth if they're chewing on their tongue.
ESET Trial & Medication Comparison
00:03:25
Speaker
Now in the small number of cases where the seizure doesn't end spontaneously, one should then proceed to use pharmacologic therapy to terminate it.
00:03:36
Speaker
It's usually not necessary to immediately intubate patients who are not intubated in a
00:03:43
Speaker
A judicious dose of a benzodiazepine in most patients will stop the seizure.
00:03:49
Speaker
If the patient already has an IV, then 0.1 milligram per kilo dose of lorazepam is appropriate for a convulsion.
00:03:58
Speaker
If the patient happens not to have an IV, then probably 10 to 20 milligrams of midazolam IM, based on the Rampart trial, would be superior to taking the time to start an IV.
00:04:11
Speaker
That's one of the things we have
00:04:13
Speaker
learned from randomized study most recently.
00:04:17
Speaker
About 65% of patients who require benzodiazepines to stop their seizure will stop seizing.
00:04:25
Speaker
Some percentage of them will go from convulsive seizure activity to non-convulsive status epilepticus.
Dosing Challenges in Seizure Treatment
00:04:33
Speaker
So if they continue to seize or they don't begin to wake up, then one would move on to second-line therapy.
00:04:41
Speaker
We're in the midst of a trial called ESET, the established status epilepticus treatment trial, that's comparing three of the usual anti-seizure drugs to see whether there's any advantage to one of them.
00:04:55
Speaker
So the drugs being tried are Phosphonatoin, 20 milligrams per kilo, Velproate, 40 milligrams per kilo, and Levataracetam, 60 milligrams per kilo.
00:05:06
Speaker
At this point, near the end of the study, we've stopped randomizing adults at the request of the DSMB because they believe we will not be able to establish the superiority of one of these agents over another.
00:05:19
Speaker
We're still randomizing children.
Causes of Seizures & Status Epilepticus Prevention
00:05:22
Speaker
The important thing to take away from that, though, is that a 60 milligram dose of levotiracetam, 60 milligrams per kilo, is a dose that is
00:05:33
Speaker
at least as safe as the others and at least as efficacious.
00:05:38
Speaker
So if you're going to use levotiracetam, you really need to use an adequate dose, giving 500 milligrams or a thousand milligrams.
00:05:46
Speaker
And considering that that's a failed dose because the patient continues to seize, really hasn't given the drug an adequate try.
00:05:55
Speaker
Within a year or so, we hope to have the
00:05:58
Speaker
results to that study ready for publication to see if there are any nuances that will be useful or to see if one of the drugs is superior when treating children.
00:06:09
Speaker
Tom, since you mentioned โ Can I interrupt and ask you a quick question?
00:06:14
Speaker
You mentioned the underdosing of levteracetam, and I think that that's not an uncommon theme with other antiepileptics, including benzos.
00:06:24
Speaker
Could you comment on that a little bit?
00:06:25
Speaker
Because I think that a lot of
00:06:27
Speaker
intensivists who are not neuro-intensivists or neurologists tend to underdose patients as they're treating the seizures.
00:06:36
Speaker
Absolutely.
00:06:37
Speaker
And we know this actually from data being collected that were done subsequently focusing on children that people are not giving adequate initial doses of abenzodiazepine, which use
00:06:56
Speaker
0.1 milligrams per kilo of lorazepam as their dose had again 65% or so effectiveness giving larger doses appears not to be more useful but giving less is not an adequate trial so focusing on lorazepam since most of the patients seen by Intensivus will already have an IV in place you need to make sure you've given an adequate dose
00:07:23
Speaker
If the patient's had a behavior change and your question is whether this could be a non-convulsive seizure and you want to give a few milligrams of lorazepam, I guess that's all right.
00:07:34
Speaker
But there's probably no downside to giving the whole dose other than some sedation.
00:07:41
Speaker
And if you haven't given it an adequate dose in convulsive status, then you've really missed the boat.
00:07:48
Speaker
And I think that there's also good evidence to suggest that
00:07:51
Speaker
intervention after the seizure has stopped in terms of preventing patients to go into status as a time-sensitive intervention and that we should be loading these patients as soon as possible, like you say, to take care of the patient, make sure they're safe.
Differential Diagnosis of Seizures
00:08:04
Speaker
Is that correct?
00:08:06
Speaker
Yeah, so it depends in part on why you think the patient had a seizure.
00:08:11
Speaker
So if someone is having one or a cluster of alcohol withdrawal seizures, for example, there's probably no advantage to putting them on a
00:08:20
Speaker
chronic anti-seizure drug.
00:08:23
Speaker
But if you think that they're seizing because they've had an acute brain injury or they have some intoxication, they have a CNS or a systemic infection, then yeah, go ahead and give an adequate loading dose of a more long-acting anti-seizure drug.
00:08:42
Speaker
And as we're talking about the initial treatment, could you mention some tips for us, for our listeners, in terms of identifying differential diagnosis that can be sometimes confused with seizures, including pseudo-seizures?
00:08:59
Speaker
Right.
00:08:59
Speaker
So I would have to start by a caveat, which is that 20 years ago, we thought we knew how to identify pseudo-seizures pretty well.
00:09:11
Speaker
And as we've gone to do more recording to prove or disprove that contention, there are a fair number of movements that we used to think of as diagnostic of pseudo seizures that can be part of real seizures or epileptic seizures, I should say.
00:09:26
Speaker
So I'm still a little reticent to label things purely on clinical grounds as being a pseudo seizure, with the exception of something that I can stop by distracting the patient.
00:09:40
Speaker
People used to think that bicycling movements of the legs were characteristic of pseudo seizures, but some frontal lobe seizures will also always produce that.
00:09:51
Speaker
Most of the time, if someone is moving both sides of their body or complaining of bilateral sensory phenomena while they're awake and responding to you, then almost all the time that will end up being a non-epileptic seizure.
00:10:09
Speaker
But one has to be pretty careful to be sure that you don't label somebody as having paroxysmal non-epileptic seizures without having EEG recording to back you up.
00:10:23
Speaker
So clearly, the role of the EEG in making a definitive diagnosis is still, I mean, the gold standard and correlating what you're seeing clinically.
Anti-Seizure Drug Efficacy
00:10:33
Speaker
That's correct.
00:10:34
Speaker
Is there, you mentioned the ISET trial, it's ongoing.
00:10:38
Speaker
So as of now, there's no clear evidence to suggest that one antiepileptic is superior to another, is that correct?
00:10:46
Speaker
Right, as the second-line drug.
00:10:49
Speaker
We're pretty sure that lorazepam is the best first-line drug, or if you don't have an IV, midazolam, based on the VA cooperative trial.
00:10:58
Speaker
But of the second-line drugs,
00:11:02
Speaker
Adequate doses of phosphatidine, valproate, or levotiracetam appear to be most likely equivalent.
00:11:09
Speaker
We won't know for sure in terms of efficacy versus safety issues that led the DSMB to stop randomizing adults.
00:11:19
Speaker
That trial does not include other agents.
00:11:21
Speaker
So for example, licosamide was not included because it didn't have an indication for pediatric use at the time that we were designing the trial.
00:11:31
Speaker
But licosamide is probably also a reasonable choice at that juncture.
00:11:39
Speaker
People have tended to use 200 to 400 milligrams as an initial dose, but
00:11:48
Speaker
The group at the Ochsner Clinic in New Orleans has suggested that a loading dose of 10 to 15 milligrams per kilo is actually what would be required and is more efficacious, but that remains to be confirmed by other studies.
00:12:04
Speaker
And it seems that one of the important points that you made earlier regarding dosing of
00:12:10
Speaker
levotiracetam is very important to reemphasize because I do see that this drug, commercially known as Keppra, seems to be utilized more and more, especially in the community hospitals.
00:12:20
Speaker
But it would seem, from what you mentioned, that people are consistently underdosing this drug.
00:12:29
Speaker
That's correct.
00:12:30
Speaker
One of the first things we do is to finish the load when we get the patient in transfer.
00:12:35
Speaker
There is a related drug newly released that is available for intravenous use called rivaracetam, but at this point we don't know where it fits into the armamentarium for status.
00:12:48
Speaker
And is there still a role for patients with status for other drugs like phenobarbital and other drugs that we've used in the past?
00:12:59
Speaker
So we do use a lot of phenobarbital, but generally
00:13:04
Speaker
after we've gotten the seizures under control since it takes a while to load.
00:13:10
Speaker
I think the 20 milligram per kilogram loading dose can be quite effective.
00:13:15
Speaker
We used to use more pentabarb in a third-line drug, but pentabarb has gotten very expensive, and I think the efficacy of phenobarbital is probably at least as good, and it seems to have less hypotension than pentobarbital does.
00:13:34
Speaker
Is there any role for propofol?
00:13:37
Speaker
So I would think of propofol as I failed the second line and now I'm going to go on to general anesthesia.
00:13:44
Speaker
So whether there's any difference between using propofol or using high-dose midazolam at a 0.2 milligram per kilo load and then starting with 0.2 milligrams per kilogram per hour as an infusion,
00:14:01
Speaker
compared to propofol at about 80 mics per kilo per minute as a starting dose, remains to be determined.
00:14:07
Speaker
There's no good comparative study in a large group of patients.
00:14:12
Speaker
If you have an anaconda available and can give an inhalational agent, one might also consider using isoflurane or desflurane.
00:14:22
Speaker
But again, these are getting into small numbers of reports as to what's efficacious.
Status Epilepticus Defined & Treatment Urgency
00:14:28
Speaker
Our practice has been
00:14:30
Speaker
in adults to usually go to propofol if the second line drug has failed and we think we need to get immediate control of the patient and status or to use midazolam.
00:14:44
Speaker
I've always been a fan of midazolam, but you have to be willing to start with a large loading dose and then continue to increase the dose.
00:14:53
Speaker
So partly it'll depend on who's going to be watching the EEG.
00:14:59
Speaker
not able to get a full-time observation of the EEG by someone who knows what they're looking at, I may opt to use propofol.
00:15:06
Speaker
Otherwise, I'll use midazolam.
00:15:09
Speaker
And I think that we mentioned status and in medicine, I think it's important to be very clear on what we're referring to.
00:15:18
Speaker
And it's not uncommon, at least when I get calls, when I'm working clinical, to hear of somebody who had a seizure, got intubated, and they're being admitted for status.
00:15:27
Speaker
Could you define for us how we really understand status epilepticus today, Tom?
00:15:32
Speaker
Sure.
00:15:33
Speaker
So in terms of an operational definition, the
00:15:37
Speaker
International League Against Epilepsy has proposed a different time for what should be considered status in order to start treatment or what should be considered the point at which status is established or refractory.
00:15:56
Speaker
So in most circumstances that would come to the attention of the intensivist or the emergency physician, five minutes of seizure activity should be considered status enough to start the benzodiazepine treatment.
00:16:09
Speaker
If the benzodiazepine succeeds, then you want to try to figure out from an etiologic standpoint what you're dealing with.
00:16:18
Speaker
So the person who goes into status because they've become abruptly hyponatremic should get their osmolality repaired in a slight degree.
00:16:28
Speaker
Whereas the person who has a brain abscess and goes into status will need anti-seizure drugs, often several of them.
00:16:38
Speaker
Once you have given that benzodiazepine, if the patient's still seizing, then you're thinking of the second line established status.
00:16:49
Speaker
And there you should try to get control of the patient within 20 to 30 minutes.
00:16:54
Speaker
That's how long it will usually take to get the drug that you need available and administered.
00:17:01
Speaker
After that, then moving on to general anesthesia.
00:17:05
Speaker
five minutes meets the definition of status as far as starting treatment, the time at which the uncontrolled seizures by themselves start to produce brain damage is probably closer to 30 minutes.
00:17:19
Speaker
So one of the reasons that initial five minutes was chosen was to have a reasonable chance of the initial treatment getting the patient under control.
00:17:32
Speaker
And because of those five minutes, I would imagine that the vast majority of seizures will last less than three minutes, two minutes.
00:17:41
Speaker
Usually, like you said, they're usually resolved by themselves.
00:17:43
Speaker
So most people who have a convulsion, it would last less than a couple minutes, correct?
00:17:46
Speaker
Right.
00:17:48
Speaker
It always seems like it lasts a long time, but when you time them out, they're usually somewhere in the vicinity of 90 seconds to two minutes.
00:17:56
Speaker
And that was also one of the...
00:17:59
Speaker
I guess, pearls that I had learned regarding pseudosezures.
00:18:03
Speaker
People would say that if seizures are very prolonged, they're more likely to be pseudoseizures than seizures.
00:18:10
Speaker
But like you said, without ENG confirmation, that would probably not be a very smart thing to put all your bet on today.
00:18:17
Speaker
Right.
Airway Management in Seizure Patients
00:18:20
Speaker
If I'm not sure, I'd say if the patient is protecting their airway,
00:18:26
Speaker
then I will try to get the EEG before I would go on to a general anesthetic regimen.
00:18:32
Speaker
I might have given the initial benzo and a second line agent.
00:18:37
Speaker
But I have seen patients who were very convincing and got to the stage of general anesthesia where it became clear with subsequent spells that their seizures were not epileptic.
00:18:50
Speaker
So one shouldn't feel bad for trying to do your best until the EEG arrives.
00:18:57
Speaker
And you mentioned in a couple of times already the airway management of these patients.
00:19:03
Speaker
My impression is that people tend to have a knee-jerk reflex to intubate somebody who's seized.
00:19:09
Speaker
And I think that often with close observation, not everybody needs to be intubated.
00:19:15
Speaker
What are your thoughts on this, Tom?
00:19:17
Speaker
So I think since most of the time, at least the 65% of the time, you'll get control with your first drug.
00:19:26
Speaker
that's often the best way to basically avoid the need for intubation to go ahead and give the lorazepam or medazolam.
00:19:37
Speaker
If the seizure is not controlled with that but the patient is still protecting their airway then I think it's fair to load them with one of the second line agents.
00:19:48
Speaker
If they are convulsing it's hard to keep them in the recovery position but if you can
00:19:53
Speaker
keep them turned to the side to try to prevent secretions from going back in the airway.
00:19:59
Speaker
On the other hand, if in that circumstance they're starting to desaturate or you're having trouble keeping the airway cleared short of intubation, then I wouldn't be shy about intubating them.
00:20:12
Speaker
The choice of drugs at that point I've always found somewhat interesting.
00:20:16
Speaker
If you know the patient was ambulatory and normal before the seizures started, then
00:20:23
Speaker
the usual rapid sequence induction is probably okay, but if there's any question in your mind about preexisting neurologic or neuromuscular disease, should probably stay away from succinylcholine because of the risk of hyperkalemia and use rocuronium or some other rapid-acting agent, if necessary, reversing it with sugamidex.
Role of EEG in Seizure Management
00:20:45
Speaker
The sedative drug that you give along with that to intubate the patient, say you're giving propylacinol,
00:20:53
Speaker
will probably stop most of the residual seizures but often for a shorter period of time in a single dose than the neuromuscular junction blocker lasts.
00:21:05
Speaker
So you don't really know that whether the patient is seizing or not until the neuromuscular junction blocker wears off in which case you might have been seizing for quite some time if it lasted 40 minutes and the propofol effect was 20 minutes.
00:21:20
Speaker
So I would say
00:21:22
Speaker
to first go ahead and try and get the EEG hooked up as quickly as possible, but also consider reversing the neuromuscular junction blocker in order to get a better exam.
00:21:36
Speaker
And in terms of treating these patients once they're intubated, if they're not waking up, should this be a concern for us?
00:21:45
Speaker
And at what point should we be concerned about potential non-convulsive status?
00:21:51
Speaker
The patient who got the 0.1 milligram per kilo dose of lorazepam will probably be somewhat sedated for a half hour or so from that, although some of them do wake up pretty dramatically.
00:22:05
Speaker
But having gone through the extra sedation of intubating them, I would usually be watching for any sign of recovery in terms of even response to noxious stimuli.
00:22:19
Speaker
If they're not responding to noxious stimuli, once the neuromuscular junction blockers are burst or worn off, I would go ahead and load them with a second line agent.
00:22:28
Speaker
Once the EEG is hooked up, then you'll have an answer to your question.
00:22:34
Speaker
If you're in a circumstance where you can't get the EEG, you've loaded with the second line agent and they're not waking up, I really don't think you can manage them without transferring them somewhere to get the EEG done.
00:22:48
Speaker
know of a way to do that.
00:22:51
Speaker
And I think that that is a problem that a lot of community hospitals face.
00:22:56
Speaker
And I have seen community hospitals try to initiate programs of continuous EEG so they don't transfer the patient.
00:23:04
Speaker
But then my question is, who's reading the EEG?
00:23:07
Speaker
Because that seems to be
00:23:08
Speaker
as difficult as just getting the logistics of the EEG connected.
00:23:12
Speaker
Could you comment in terms of ideally when would you think that so the EEG really should be done within the first 12 hours or initiated within the first 12 hours of this whole sequence is that correct?
00:23:24
Speaker
Oh I would want to do it sooner than that.
00:23:27
Speaker
I'd say the future of this field now there are a couple of devices that are sort of quick connect limited montage EEGs
00:23:39
Speaker
that I think people should consider if they can't get a standard EEG hooked up 24-7.
00:23:48
Speaker
We have yet to actually study these devices in status, but there are already some published studies using them in emergency departments and other parts of the hospital to show that they are quite efficient at
00:24:05
Speaker
both being attached by non-trained technologists, it can be attached by physicians, nurses, respiratory therapists fairly quickly, and they can also send the EEG data to a central reader over the internet so that if you acquire one of these devices and have the reader available off-site, you could probably manage the patient without the transfer.
00:24:32
Speaker
And these are rapid sequence terms that they have less number of channels, is that correct?
00:24:39
Speaker
And they're easier to place?
00:24:41
Speaker
Right.
00:24:43
Speaker
So one of them, for example, actually two of them have just eight contacts, so you get four channels on each side.
00:24:53
Speaker
when people have studied what happens when you reduce the montages, you miss some of the information, but if your question is whether the patient's gone into non-convulsive status, they are, in my mind, quite useful and can at least answer the question in the short term so that you know whether you need to proceed or not.
00:25:13
Speaker
So it's much more like, I guess, the analogy would be when you're doing a point-of-care ultrasound to answer a specific question, yes or no.
00:25:21
Speaker
Do they have a pericardial diffusion, yes or no?
00:25:24
Speaker
I mean, obviously, there's a lot of detail that might not be there, but for a dichotomous question or binary question, it can be very helpful in terms of managing the patient at that point.
00:25:31
Speaker
Exactly.
00:25:33
Speaker
Exactly.
00:25:35
Speaker
And in terms of continuous EEG, how long, I guess it depends, but what would be the minimum that you would continue this for 48 hours once the seizures have stopped?
00:25:45
Speaker
I mean, what's the usual recommendation, Tom, these days?
00:25:49
Speaker
Right, so again, the data that have been collected aren't specifically for patients who are in status, but if you look at studies of patients in ICUs with various brain injuries,
00:26:04
Speaker
of the ones who will have seizures you picked up about 90% of them with 24 hours of monitoring and about 95% with 48 hours.
00:26:14
Speaker
Going from 48 to 72 you only pick up another 3% or so.
00:26:18
Speaker
So you can basically look at the data and decide if you're content with 90 or 95 or 98%.
00:26:25
Speaker
Of course if the patient is improving and you can follow them clinically then
00:26:32
Speaker
At that point, you can disconnect the EEG.
00:26:34
Speaker
These are for people who remain poorly responsive.
00:26:40
Speaker
So another area that I think creates a lot of confusion amongst intensivists outside of the neuro ICU has to do with potential seizures, non-convulsive seizures, and other abnormal waveforms that identify an EEG post-anoxic brain injury after cardiac arrest and after patients have undergone targeted temperature management.
EEG in Temperature Management & Prognosis
00:27:03
Speaker
So the first question I have for you, Tom, in this area is, should every patient that has targeted temperature management
00:27:09
Speaker
be followed with continuous EEG?
00:27:15
Speaker
So first let me say that I do that.
00:27:19
Speaker
I think that is the best way to manage them, to know if they're having any seizures even if they're getting neuromuscular junction blockade for shivering.
00:27:29
Speaker
If you are not giving a neuromuscular junction blockade, you may miss some non-convulsive seizures as they're warming up if you don't do EEG monitoring
00:27:41
Speaker
My own bias is that the patient who has seizures should be treated for them, but that we shouldn't be giving prophylactic anti-seizure drugs in the absence of seizures.
00:27:55
Speaker
There's a very good study from the EEG group at Northwestern that looked at
00:28:02
Speaker
the myoclonic activity that is sometimes seen when patients are either being cooled or more likely when they're being rewarmed.
00:28:10
Speaker
And based on the EEG recordings they've done and other people have done, we really don't think that the myoclonic activity in most cases represents seizure activity.
00:28:21
Speaker
It's coming from some lower center.
00:28:25
Speaker
And the group from Northwestern has also published a nice study looking at the phenotype of these myoclonic movements and providing guidance on which movements are likely to portend a poor outcome versus those in which some of the patients have made good recoveries.
00:28:47
Speaker
Last author of that is Stefan Shula at Northwestern, and it's worth consulting if you're dealing with a patient who has myoclonus after a cardiac arrest.
00:28:57
Speaker
And I think that's a very โ we'll put the reference in the show notes.
00:29:01
Speaker
But I was going to actually ask you this specifically because I often see intensivists mention that the presence or when they see myoclonic movement in post-arrest patients, no matter where it is in the time frame,
00:29:17
Speaker
to immediately associate that with a very poor prognosis.
00:29:21
Speaker
And my understanding has always been that what has been shown to really be a very bad prognosis before the area of hypothermia was myoclonic status epilepticus, which is an EEG diagnosis.
00:29:32
Speaker
And I've never seen that.
00:29:33
Speaker
Could you comment on that?
00:29:36
Speaker
Yeah, so very few post-arrest patients have real status epilepticus.
00:29:40
Speaker
They may have repetitive myoclonus, but it doesn't respond to anti-seizure drugs,
00:29:47
Speaker
It doesn't have the typical evolution of a seizure.
00:29:52
Speaker
And unfortunately, the American Academy of Neurology's guidelines and practice parameters in the past didn't distinguish these very clearly.
00:30:03
Speaker
I think the ones that are currently under review will do a better job of distinguishing that.
00:30:08
Speaker
If somebody has real seizures,
00:30:12
Speaker
based on EEG and by the evolution of their clinical picture, I would certainly treat that.
00:30:19
Speaker
There are recent publications suggesting that having seizures is bad, but not completely damning in your prognosis.
00:30:29
Speaker
By the way, we mentioned that we're really coming around to sort of regardless of any clinical findings, one should wait for about three or more days after
00:30:41
Speaker
rewarming before prognosticating that people who remain unresponsive with poor cranial nerve function have still begun to awaken in seven days and had a good outcome.
00:30:53
Speaker
So I think there's been a lot of premature termination of aggressive treatment for these patients.
00:31:00
Speaker
David Greer, who's now at Boston University, has done some very good work in this area, and there are more publications coming out every month.
00:31:08
Speaker
Absolutely.
00:31:09
Speaker
I think that with the advent of target temperature management, we've changed the old natural evolution or course of this disease of anoxic brain injury.
00:31:19
Speaker
And I do believe that today we have to wait more time.
00:31:24
Speaker
And I think a lot of people attribute findings as being prognosticator when they really aren't in that timeframe.
00:31:31
Speaker
And that's something that we've talked in a previous podcast episode with Fred Rincon, which I think is very important.
00:31:38
Speaker
So, Tom, one of the things that always comes to mind when I think of these patients is, are seizures just a byproduct of the damage and they just represent how poorly this patient would do?
00:31:51
Speaker
Or are there something that are treatable, especially when these are non-convulsive seizures or when we see PLEDS or BIPLEDS on the EEG, post-anoxic brain damage?
00:32:01
Speaker
Are these things that just represent a poor outcome or should they be treated aggressively?
00:32:07
Speaker
Well, so...
00:32:08
Speaker
Having either seizures or the repetitive EEG complexes that you've just mentioned carry a worse prognosis than not having them.
00:32:21
Speaker
But the thing on the EEG that is most useful in terms of prognostication actually is whether the background activity changes when you give sensory stimulation.
00:32:34
Speaker
So that whether it gets
00:32:36
Speaker
desynchronized meaning gets faster and lower in amplitude or shows what people have always called paradoxical responses where the sensory stimulation results in big slow waves.
00:32:49
Speaker
Any stimulus given either auditory or somatosensory that causes a change in the EEG means that signal is getting to the cortex and the cortex is making a response.
00:33:02
Speaker
And that looks to be the best
00:33:04
Speaker
single predictor of a good outcome in the patient who's been cooled after cardiac arrest.
00:33:11
Speaker
In the pre-hypothermia era, the presence or absence of the N20 response to somatosensory evoked potential testing was thought to be the single best predictor.
00:33:24
Speaker
But there have now been numbers of patients who lacked that response early on who went on to make good recoveries.
00:33:32
Speaker
So right now we would say that EEG reactivity is the single best.
00:33:36
Speaker
There have been a couple of studies in recent years that look at combinations of variables.
00:33:44
Speaker
The EEG responsiveness, the N20, perhaps adding either neuron-specific enolase or tau measurements in serum to try and improve that.
00:33:55
Speaker
The tau is still fairly experimental, but the TTM group
00:34:00
Speaker
in Scandinavia just published a large number of such patients.
00:34:05
Speaker
So I think we're going to be improving our prognostication.
00:34:10
Speaker
But right now I'd say EEG reactivity is the single most important thing to look for.
00:34:14
Speaker
Just having periodic complexes or seizures by themselves don't mean you can't recover, though.
00:34:21
Speaker
So let me ask you, in terms of how you utilize EEG during your treatment of patients with anoxic brain injury,
00:34:28
Speaker
So I presume from what you told me earlier that as you initiate the treatment, while you get them to target temperature and during the time that you are at target temperature and rewarming, you have continuous EEG.
00:34:42
Speaker
Is that correct?
00:34:43
Speaker
Yes.
00:34:44
Speaker
Once they are rewarmed, if the EEG is not showing you any seizure activity, do you stop the EEG at that point and give them some time to see what happens?
00:34:55
Speaker
Yes.
00:34:55
Speaker
I think if there's no seizure activity going on,
00:34:59
Speaker
Other than looking to see whether there's reactivity, say once they're rewarmed, I don't feel compelled to continue the EEG recording.
00:35:09
Speaker
If they have phenomena that nobody can explain easily, though sometimes seizures are just producing autonomic changes.
00:35:17
Speaker
So I'd say I haven't done this formally, but probably half of the patients
00:35:24
Speaker
do stay on EEG for one or more days after they're rewarmed just for us to watch what's going on.
00:35:31
Speaker
And I think it's a very common practice in many hospitals that as people are trying to prognosticate, like you mentioned earlier, we wait a little bit longer or there's a tendency to wait longer now after hypothermia.
00:35:43
Speaker
But at one point, it almost seems that nobody can be pronounced as a poor outcome without an EEG.
00:35:49
Speaker
And you did mention what are the findings on the EEG,
00:35:52
Speaker
that are most useful in that perspective.
00:35:55
Speaker
But at what time would you do an EEG again?
00:36:00
Speaker
Well, I would say if I'm getting ready to counsel the family that this seems like it's a very poor prognosis, I might look again for reactivity.
00:36:15
Speaker
Other than that, if I'm not suspicious of seizures, I probably wouldn't look it up again.
00:36:21
Speaker
I think there's a...
00:36:23
Speaker
One useful thing on the horizon, again from David Greer's group, suggesting that a good long-term prognostic study will actually be a quantitative apparent diffusion coefficient measurement on the MRI.
00:36:41
Speaker
And I think he's published one paper looking at this that establishes some thresholds other people need to look at it.
00:36:49
Speaker
But if I were looking toward the future,
00:36:53
Speaker
Where we're going with this, I'd say that the quantitative ADC of the MR will probably be the best single radiographic parameter and something that you could do once you've rewarmed somebody and now you're in the situation of trying to figure out what should I do.
00:37:13
Speaker
Absolutely.
00:37:13
Speaker
And I think that this is obviously an area that has evolved significantly since we started doing hypothermia.
00:37:20
Speaker
And there's a lot still that we don't know and a lot of, I don't want to say controversy, but maybe variability in how people are approaching this.
00:37:29
Speaker
But it is important to be able to give that information to families.
00:37:32
Speaker
And I do think that a point that our audience should take home is the use of EEG and the reactivity in the EEG as being a positive sign
00:37:42
Speaker
potential cortical function as opposed to what we used to look for before which were very omnious or negative signs that pretend of a no chance of recovery.
00:37:51
Speaker
I agree.
00:37:53
Speaker
So I think that this is all been very super interesting and I think be very useful for for our clinicians.
00:37:59
Speaker
We talked a little bit about how to first deal with seizures, what are the first line, second line, and some third line agents and
00:38:06
Speaker
talked about what status really constitutes and how to deal with it.
00:38:10
Speaker
I think this conversation on EEG is a fascinating one, especially outside of the confines of academic centers and neurointensive care units.
00:38:18
Speaker
I think that there's a lot of discussion of whether we should have EEG, who's going to read it.
00:38:23
Speaker
Hopefully, the role of telemedicine and, like you said, these new technologies will make it available to more patients sooner.
00:38:31
Speaker
But I do agree, Tom, I think an important point for our clinicians is that
00:38:36
Speaker
If you don't have capacity to do EEG and read them and you have a patient who you're treating for status, they probably should not stay in that hospital, should go to a place where that can be provided as soon as possible.
00:38:48
Speaker
And I think that's an important point as well.
00:38:51
Speaker
I really want to be respectful of your time.
00:38:54
Speaker
And one of the things that we usually do as we wrap up is we try to ask a couple of questions that really explore the wisdom and other aspects of practicing critical care from our guests.
00:39:06
Speaker
Would that be okay?
00:39:08
Speaker
Absolutely.
Book Recommendation & Insights
00:39:09
Speaker
So the first question, Tom, is what book or books have influenced you the most or what book have you gifted most often to others?
00:39:18
Speaker
Well, clearly the book I have gifted most often is not medical.
00:39:23
Speaker
It's the spy novel Tinker Tailor Soldier Spy by John Le Carre, which is not only a great mystery read but has a
00:39:33
Speaker
all sorts of insights into human behavior that I think are quite prescient and I end up quoting much of the time.
00:39:42
Speaker
And I have not read that, but we'll definitely put it in the show notes and I'll put it on my list.
00:39:46
Speaker
And I think that one of the things that I've learned from asking this question, Tom, is that a lot of us undervalue the amount that we can learn of human behavior from fiction.
00:39:59
Speaker
And I think it's a wonderful venue to, like you said, learn about what moves people and how people behave.
00:40:06
Speaker
So definitely this is something that we'll want to explore.
00:40:12
Speaker
The second question has to do with, is there anything that you believe to be true that most other people don't believe?
Skepticism on Randomized Trials
00:40:21
Speaker
Well, I've not done a formal poll
00:40:28
Speaker
among my friends and colleagues, but I'm getting more and more skeptical of the ability of randomized trials to answer questions in the intensive care unit because the control group doesn't just sit there and wait for them to either die or recover.
00:40:47
Speaker
In each case, we're trying to do our best for all the other things we do for the patient, even if they're in the, of course, we don't know if they're in the placebo arm.
00:40:58
Speaker
studies for example in subarachnoid hemorrhage looking at drugs like nicartipine have come to the conclusion that the drug is not useful.
00:41:10
Speaker
Well if you look at the quote unquote control group in the two intravenous nicartipine trials in subarachnoid hemorrhage, those patients got lots more rescue therapy than the ones who got nicartipine.
00:41:23
Speaker
So yes there was no difference in outcome but that doesn't mean
00:41:27
Speaker
the drug didn't work.
00:41:28
Speaker
And then if you start to look at almost everything else we do, patients in the fluid and catheter treatment trial, for example, well, yeah, there was a difference in their time to wean from the ventilator, but there were still many differences in the way the patients were treated based simply on what did they need at the moment.
00:41:50
Speaker
Yeah.
00:41:51
Speaker
And I think, go ahead.
00:41:53
Speaker
In that trial, I see in that trial,
00:41:56
Speaker
Mark Mickelson at Penn did a follow-up, a neuropsychological study showing that the patients in the liberal fluid arm had better neuropsychological function a year later, even though we think that it was good to be in the conservative arm and get off the ventilator faster.
00:42:12
Speaker
So I'm starting to think that we are gonna need to have smaller, very focused trials that the populations we're dealing with are really not amenable to large randomized trials.
00:42:26
Speaker
And I think that you mentioned this topic.
00:42:29
Speaker
It's something that I've been thinking about in terms of every year we go to national conferences and
00:42:35
Speaker
either one of two things happens.
00:42:37
Speaker
Either they present negative studies that make you wonder, like you said, or even worse, they present a study that doesn't change anybody's mind because of confirmation bias, right?
00:42:46
Speaker
So people who believe something works, no matter what you show them, believes it still works.
00:42:51
Speaker
And people who didn't believe in it, no matter what you show them, still don't believe.
00:42:55
Speaker
And I think that not only the scientific value of really answering questions, but the ability that trials have
00:43:04
Speaker
the few times they are positive, to change behavior I think is also very interesting.
00:43:11
Speaker
The final question relates, Tom, to what would you want every intensivist who's listening to this podcast to know?
Advances in Neurocritical Care
00:43:21
Speaker
So I've been a full-time neurointensivist since about 1989.
00:43:28
Speaker
And when I look at what we did then compared to now and
00:43:32
Speaker
not just the survival but the functional outcome of patients.
00:43:37
Speaker
Patients with devastating neurologic injuries of various sorts really do so much better now than they did back in the 1980s that, you know, it's a miracle to me to see them.
00:43:51
Speaker
When you're going to work every day, you don't see that incremental change because, you know, no day has a breakthrough in it.
00:44:01
Speaker
simply paying better attention to these patients and not assuming that, well, they're devastated, they're going to do poorly, and working hard to try and improve their outcomes is really worthwhile.
00:44:13
Speaker
And I have to say, I've really been proud to see the growth of the field and also the acceptance of neurocritical care principles by intensivists of other fields.
00:44:26
Speaker
We now have very good interactions
00:44:30
Speaker
across the Society of Critical Care Medicine, the American Thoracic Society, Society for Neurosurgical Anesthesia and Critical Care, even the American Academy of Neurologic Surgeons.
00:44:41
Speaker
So some days seem like they're very depressing, but
00:44:46
Speaker
things really are a lot better and they'll continue to get better.
00:44:50
Speaker
And I think that what you mentioned, Tom, which is very, very important, speaks to the fact that we tend to overestimate what we expect on the short term, but turn to underestimate what can happen over a long period of time.
00:45:03
Speaker
And like you said, I mean, from 1989 to 2018, the advances in how we care for these patients and for the field of neurocritical care are really remarkable.
00:45:13
Speaker
And I think that we're going to learn.
00:45:16
Speaker
There's a lot of exciting studies that are ongoing and hopefully we'll continue to learn how to treat the brain because at the end of the day, it's the only organ that really matters, right?
00:45:27
Speaker
Well, if it doesn't work, the others don't matter at all.
00:45:30
Speaker
Okay.
00:45:31
Speaker
Absolutely.
00:45:32
Speaker
Well, Tom, it was a real pleasure talking with you about these topics.
00:45:36
Speaker
I wanted to thank you for sharing your time and your knowledge with us.
00:45:40
Speaker
Hopefully, we'll be able to have you back on the podcast soon.
00:45:43
Speaker
And again, thank you very much for your time.
00:45:46
Speaker
I appreciate it.
00:45:47
Speaker
Thank you for the invitation.
00:45:51
Speaker
Thanks again for listening to Critical Matters.
00:45:53
Speaker
Make sure to subscribe to this podcast on iTunes or Google Play.