Become a Creator today!Start creating today - Share your story with the world!
Start for free
00:00:00
00:00:01
Neuroprognostication after Cardiac Arrest
12 Plays3 years ago
Patients who survive a cardiac arrest often sustain a severe anoxic brain injury. Determining their neurological prognosis is a critical component of post-cardiac arrest care. In this episode of the podcast, we will discuss best practices for Neuroprognostication after Cardiac Arrest. Our guest is Dr. Neha Dangayach, a neurocritical care physician at Mt. Sinai Medical Center in New York. Dr. Dangayach is an Assistant Professor of Neurology and Neurosurgery at the Icahn School of Medicine at Mt. Sinai.
Additional Resources:
Predicting outcome from hypoxic-ischemic coma. Levy DE, et al. JAMA 1985: https://pubmed.ncbi.nlm.nih.gov/3968772/
Prediction of poor neurological outcome in comatose survivors of cardiac arrest: a systematic review. Sandroni C et al. Intensive Care Medicine 2020: https://pubmed.ncbi.nlm.nih.gov/32915254/
Books Mentioned in this Episode:
How to Win Friends & Influence People. By Dale Carnegie: https://amzn.to/3Lk9rpn
Dare to Lead. By Brene Brown: https://amzn.to/3vi1dse
Think Again. By Adam Grant: https://amzn.to/3OB3l6a
Recommended
Transcript
Introduction to the Podcast
00:00:06
Speaker
Welcome to Critical Matters, a sound podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:14
Speaker
Sound provides comprehensive critical care programs to hospitals across the country.
00:00:19
Speaker
To learn more about our programs and career opportunities, visit www.soundphysicians.com.
00:00:26
Speaker
And now
Episode Focus and Guest Introduction
00:00:27
Speaker
your host, Dr. Sergio Zanotti.
00:00:32
Speaker
Patients who survive a cardiac arrest often sustain severe anoxic brain injury.
00:00:37
Speaker
Determining their neurological prognosis is a critical component of post-cardiac arrest care.
00:00:42
Speaker
A balanced evidence-based approach to neuroprognostication is needed to avoid premature withdrawal of support in potential survivors and to avoid the other extreme of prolonged life support in truly hopeless cases.
00:00:55
Speaker
In today's episode of the podcast, we will discuss breast practices and neuroprognostication after cardiac arrest.
00:01:02
Speaker
Our guest is Dr. Nihat Tangayak, a neurocritical care physician at Mount Sinai Medical Center in New York.
00:01:08
Speaker
She's an assistant professor of neurology and neurosurgery at the Icahn School of Medicine at Mount Sinai.
00:01:14
Speaker
Dr. Tangayak serves as a director of Neuroemergencies Management and Transfers, NEMAT, for the Mount Sinai Health System.
00:01:21
Speaker
She's also the Neurocritical Care Fellowship Director and Research Co-Director for the Institute of Critical Care Medicine.
00:01:27
Speaker
She is also a co-director of the Mount Sinai Hospital's Neurosurgical ICU
00:01:32
Speaker
It's a true honor and a pleasure to have her on the podcast.
00:01:35
Speaker
Niha, welcome to Critical Matters.
00:01:38
Speaker
Thank you so much, Sergio, for the kind introduction.
00:01:40
Speaker
Really looking forward to our conversation today.
00:01:42
Speaker
Absolutely.
Evolution of Neuroprognostication
00:01:43
Speaker
And the last several months, I would say, the world of post-cardiac arrest obviously has been shocked by the TTM2 trial, but we're not going to talk about that precisely today.
00:01:56
Speaker
I think we're going to talk of a topic that perhaps is
00:02:00
Speaker
as important or more important because it's an opportunity, I believe, for optimization, for standardization, and for a lot of practices to really come up with evidence-based protocols to do it in a more consistent way.
00:02:12
Speaker
And that is really trying to determine the prognosis of survivors of cardiac arrest and neuroprognostication, which I think is still a big challenge for a lot of intensivists, and I'm sure as well for neurointensivists.
00:02:28
Speaker
What I would like to do, maybe start with an introduction in terms of an historical context.
00:02:33
Speaker
In 1985, Fred Plum and his team published probably a seminal paper of determining prognosis of patients who suffered non-traumatic anoxic brain injury.
00:02:44
Speaker
And for decades, that has dictated what we do.
00:02:47
Speaker
But then things changed with hypothermia.
00:02:49
Speaker
We learned a lot.
00:02:50
Speaker
And now things might be changing again.
00:02:52
Speaker
So maybe if you could just give us a brief overview
00:02:56
Speaker
of that journey as we begin this conversation.
00:03:00
Speaker
Certainly, and I think what I'm hoping to do throughout our conversation is also share a framework for how to think about neuro prognostication as a whole.
00:03:09
Speaker
What does multimodal prognostication refer to and how did we even come to this point for different kinds of severe acute brain injuries and specifically for hypoxic ischemic brain injury or hypoxic ischemic encephalopathy.
00:03:26
Speaker
And we've come a long way since that historical paper from Bloom that you referred to about neuro prognostication.
00:03:35
Speaker
And I almost feel that our ability to be certain about neuro prognostication has decreased with the
00:03:45
Speaker
the evolution of our understanding of how the primary neurological injury, that hypoxic ischemic brain injury occurs and how the secondary neurological injury contributes to cumulative burden of injuries, including systemic injuries in these post-cardiac arrest patients.
00:04:04
Speaker
So I want to lay that out there that our ability to be certain has decreased with evolving literature.
TTM Trials and Fever Prevention
00:04:13
Speaker
So it's almost as if
00:04:14
Speaker
the more we know, the less certain we become.
00:04:19
Speaker
So with that in mind, with the TTM adoption, all of those different studies that led to TTM becoming our standard of care, there wasn't a whole lot that we could have done to improve outcomes for patients post-cardiac arrest.
00:04:38
Speaker
So when the Haka study and the Bernhardt study were released, this was a very hopeful moment.
00:04:45
Speaker
For the first time for post-cardiac arrest survivors, there was something dramatic that we could do to improve mortality and potentially improve outcome.
00:04:55
Speaker
And then with TTM1 in 2013 and now TTM2 and several other studies in between these studies, again,
00:05:07
Speaker
I do want to share that the studies, both Nielsen as well as our TTM2 study now, these are not studies looking at TTM versus no TTM.
00:05:17
Speaker
These are studies that look at TTM, one specific temperature target versus another specific temperature target.
00:05:25
Speaker
The reason why it's important to keep that at the back of our minds when we think about neuro prognostication, because
00:05:32
Speaker
I think of fever as a surrogate marker for a lot of other processes that we're not able to measure when we want to quantify the underlying neurological injury.
00:05:43
Speaker
So that primary injury, that HIB or hypoxic ischemic encephalopathy, that's already occurred.
00:05:49
Speaker
There are things that you can do, peri-arrest, intra-arrest, post-arrest, to improve neurological outcomes.
00:05:58
Speaker
And prevention of fever,
00:06:00
Speaker
by instituting TTM is one of those things because we know that fever in patients with all kinds of severe acute brain injury, including post-cardiac arrest brains, is very harmful.
00:06:13
Speaker
It's leading to excitotoxic mechanisms, activation of inflammatory cascades, calcium influx, glutamate excitotoxicity.
00:06:22
Speaker
So there's a lot of things that are happening to brains after severe acute brain injury.
00:06:27
Speaker
Hence, the importance to keep that at the back of our mind that you may choose whatever target you want to choose, but at least fever prevention is going to be important because that is one of those things which is in our hands by being intentional, by instituting those good practices, we give our patients the ability and the opportunity to have a better neurological outcome.
Multimodal Neuroprognostication
00:06:51
Speaker
With respect to neuro-prognostication, one thing that hasn't changed
00:06:57
Speaker
is multimodal neuroprognostication.
00:06:59
Speaker
All of those different things, because not a single test, not a single biomarker, not a single imaging study is going to give us 100% sensitivity or specificity.
00:07:11
Speaker
And we've got to be absolutely sure because the difference between life and death, the difference between life as we know it and the new state of normal that our postcardiac arrest survivors have
00:07:24
Speaker
will experience is going to be determined by what we do and how we leverage all these different things right from clinical exam, biomarkers, imaging studies, electrophysiological studies.
00:07:37
Speaker
So that component hasn't changed.
00:07:40
Speaker
So from a historical perspective, moving from 1985 right up to 2022, just to summarize,
00:07:52
Speaker
One thing that hasn't changed is multimodal prognostication.
00:07:58
Speaker
Another thing that has changed is certainty in who is going to have a good outcome versus who's going to have a poor outcome.
00:08:07
Speaker
We know that about 80% of our post-cardiac arrest patients are going to arrive in a comatose state.
00:08:15
Speaker
And about two thirds of these patients will not survive their hospitalizations.
00:08:19
Speaker
And most of those patients who don't survive
00:08:22
Speaker
don't survive because of withdrawal of life-sustaining therapies.
00:08:25
Speaker
So if that's the case, then it behooves us to be as sure as we can be.
00:08:31
Speaker
And that brings me to my third point is prognostic humility.
00:08:37
Speaker
Prognostic humility being humble about the uncertainties that come in prognostication.
00:08:43
Speaker
This applies to all severe acute brain injuries, but specifically for post-cardiac arrest survivors.
00:08:49
Speaker
And taking all of the data we have,
00:08:52
Speaker
putting it in the context that is available to us at this moment in time and coming up with the best possible neuro prognostication or estimate of neuro prognostication and shared decision making so that we can uphold the goals, values and wishes of that patient while we're guiding that patient's loved ones or family members in making some of these decisions.
Diagnostic Humility in Prognostication
00:09:14
Speaker
So, Sergio, I hope this was helpful in navigating that historical perspective and bringing it to how we look at post-cardiocardial prognostication now.
00:09:27
Speaker
Absolutely.
00:09:27
Speaker
I think it's a great starting point to try to then go into the neuroprognostication approach.
00:09:34
Speaker
But before we go there, Neha, I do want to touch on a couple of things that you mentioned and maybe dig a little bit more into
00:09:41
Speaker
So the first thing that really struck me as you were talking and really thinking about this also from my experience as a clinician that now has more gray hair is what you were saying in terms of our diagnostic humility.
00:09:54
Speaker
And the first thing that came to mind is a famous Bertrand Russell quote that the whole problem with the world is that fools and fanatics are always so certain of themselves and wiser people so full of doubt, right?
00:10:05
Speaker
Absolutely.
00:10:07
Speaker
As we learn more and more, I think doubt is very important in our practice because these are very serious issues.
00:10:14
Speaker
It's somebody's life, it's somebody's loved one's life.
00:10:17
Speaker
And one of the problems that I think we have seen, at least by studies and probably experience in our practices, is the whole concept of self-fulfilling prophecies in this population with very bad outcomes as a whole, like you said.
00:10:32
Speaker
But very early, we interpret a sign as being a dismal sign of prognosis
00:10:38
Speaker
our care immediately starts going in the direction of not supporting those patients.
00:10:42
Speaker
And by definition, it becomes a self-fulfilling prophecy.
00:10:45
Speaker
And we have to be very careful because as we'll talk today, I believe that there are a lot of misconceptions.
00:10:52
Speaker
There's a lot of mistimed interpretations.
00:10:56
Speaker
And not only should we be using multimodality, but I think another very important aspect of this whole enterprise is time.
00:11:04
Speaker
And time in terms of a serial,
00:11:07
Speaker
evaluations, but also timing in relation to the event to really understand what's going on.
00:11:13
Speaker
And I'm sure that we'll touch on those a little bit more.
00:11:16
Speaker
You're absolutely right about the self-fulfilling prophecies and time.
00:11:21
Speaker
And if we're not careful, and if we're not intentional, we may not only predispose ourselves to making the wrong decision, but it is our responsibility to guide patients, families, and other
00:11:34
Speaker
you know, subspecialists who we are working with to provide patient-centered care to do the right thing.
00:11:41
Speaker
And I'll often say, you know, I'll share this during our family meetings in prognostication, I will acknowledge the uncertainty right at the outset.
00:11:51
Speaker
that we don't know what the future holds, but this is the information that we have in this particular moment in time.
00:11:59
Speaker
And both understanding what has happened with respect to that primary neurological injury.
00:12:04
Speaker
So some of the tests that we do, including our imaging tests, including EEG, including biomarkers, including the clinical exam, that's to be able to quantify, okay, what's happened with that primary neurological injury or HIB or HIE, and then,
00:12:19
Speaker
what is going to happen as part of that, the secondary neurological injuries, whether it's cerebral edema, status epilepticus, whether it's sepsis associated encephalopathy or multifocal infarcts from hyperperfusion or that AKI, CRRT related, you know, dialysis associated neurological injury.
00:12:39
Speaker
There's so much more that happens to these patients that for us to try to prognosticate very early in someone's course,
00:12:48
Speaker
may not be the right thing to do unless, and we'll talk more about what some of those markers could be that tell us, okay, this person's not going to have a good neurological outcome, but a majority of our patients are then going to be in that situation where we cannot be certain and we've got to support them.
00:13:07
Speaker
And going back to Sergio's point about time, for how long do you then support
Factors Affecting Prognostication
00:13:12
Speaker
them?
00:13:12
Speaker
Current guidelines say at least waiting
00:13:15
Speaker
72 if not longer hours, particularly if you have confounders on board, the sedatives that you've used and the metabolism that's delayed because of hepatorenal dysfunction, et cetera.
00:13:25
Speaker
So just keeping those things at the back of our minds, not being rigid when we're using these frameworks, both with respect to our interpretation of the findings on different studies as well as time.
00:13:38
Speaker
So yes, we want to do serial assessments.
00:13:41
Speaker
We want to understand accumulatively what is happening to our patients as we continue to intentionally prevent this burden of secondary neurological injury.
00:13:52
Speaker
But you don't want to prognosticate too early because you may also falsely say that somebody is going to have a good outcome if you haven't waited long enough.
00:14:01
Speaker
And on the other extreme, similarly say that somebody is going to have a poor outcome if you haven't waited long enough.
00:14:08
Speaker
Excellent.
00:14:08
Speaker
So let's go into the approach.
00:14:11
Speaker
And what I would like to start with is with every time, and I was working clinically yesterday and I had a cardiac arrest patient transferred to our hospital.
00:14:21
Speaker
And every time somebody calls me about a cardiac arrest, where it's the ED or transferring hospital, there are always elements of the history that they emphasize as prognostic factors like, oh, this is really bad or this is really, really good.
00:14:38
Speaker
And I wanted to ask you, are there elements in the clinical history that are truly helpful?
00:14:44
Speaker
That's a great question.
00:14:45
Speaker
And yes, there could be.
00:14:47
Speaker
And again, we won't take that in isolation as compared to everything else that's happening to our patients.
00:14:53
Speaker
But it's important to know who is this patient who had a cardiac arrest?
00:14:56
Speaker
Who's the person behind the patient?
00:14:58
Speaker
Of course, age is a marker, but it is not the only marker of how somebody is going to do after any kind of brain injury.
00:15:08
Speaker
but knowing yes, okay, so what's somebody's age?
00:15:11
Speaker
What is their pre-morbid functional status?
00:15:15
Speaker
What is their comorbidity burden?
00:15:18
Speaker
Are they dependent on any organ replacement therapies, dialysis or not?
00:15:22
Speaker
So just knowing who the person is before they had that cardiac arrest.
00:15:26
Speaker
The second component is, you know, the characteristics of the arrest itself, were they found down?
00:15:33
Speaker
Do we know when they were last seen normal?
00:15:37
Speaker
Of course, that initial rhythm, how long did it take?
00:15:40
Speaker
What was their ROSC time?
00:15:42
Speaker
And did they have multiple arrests in the field or not?
00:15:46
Speaker
Or in the ED that's calling you for a transfer?
00:15:50
Speaker
All of those things are important, but again, whether somebody had a B-Fib arrest or whether somebody had a PEA or they were found in asystole,
00:15:59
Speaker
you know, knowing those pieces are important because they may give us some clues about what is going to happen next.
00:16:06
Speaker
However, in isolation, it's very hard to just say, okay, somebody is older and they're a nursing home resident and they were found down.
00:16:13
Speaker
Now what is going to happen?
00:16:15
Speaker
When I listened to that, yes, at the back of my mind, I'm thinking the probability of a poor outcome is higher.
00:16:21
Speaker
Then comes this third component of,
00:16:25
Speaker
do you already have access to information or collateral information from their surrogates?
00:16:31
Speaker
Do they have a priority stated advanced directives or not?
00:16:35
Speaker
And would they want heroic measures or not?
00:16:38
Speaker
And what is a meaningful quality of life for them?
00:16:41
Speaker
So typically when we'll get called for prognostication, it's usually after ROSC.
00:16:45
Speaker
So yes, I will ask for all of those historical pieces so I can begin to build the story
00:16:52
Speaker
while we are waiting for other pieces of objective data.
00:16:57
Speaker
Now, let me ask you a question in terms of is there any data to support this or am
Care Variability and CPR Quality
00:17:03
Speaker
I wrong?
00:17:03
Speaker
But my clinical observation has been two things I find consistently.
00:17:09
Speaker
One is that the downtime is often inaccurate.
00:17:14
Speaker
And since we don't know the quality of CPR that somebody truly got, it might not really be that determined in terms that
00:17:22
Speaker
You could have somebody who had a short downtime but with very poor CPR, or you could have somebody who arrested in the OR with an A-line and excellent CPR for a prolonged period of time, right?
00:17:32
Speaker
And at the end, I mean, there may be very different divergent outcomes.
00:17:36
Speaker
And the second one that I wanted to ask you, Niha, was it does seem that when the mechanism of cardiac arrest is from asphyxia or anoxic respiratory failure,
00:17:47
Speaker
the outcome obviously usually is going to be on average worse because by the time the heart stops, they already are severely hypoxic.
00:17:54
Speaker
Is there any data to support that?
00:17:58
Speaker
So first I'll, you know, talk about the variabilities in care that you highlighted.
00:18:03
Speaker
So CPR quality.
00:18:05
Speaker
So it's not just about the time in that situation because there is so much care variability, whether it's CPR quality, whether it's TTM quality, whether it's
00:18:15
Speaker
the kind of monitoring, the kind of multimodal organ support that is being provided to these patients.
00:18:22
Speaker
There is so much variability in how we deliver care depending upon different care settings.
00:18:29
Speaker
And these variabilities are often not measurable because nobody is paying attention to observing how different these things may be.
00:18:40
Speaker
We're lucky that sometimes we may get automated feedback regarding CPR in the middle of arrest depending upon the defibrillator devices we use.
00:18:51
Speaker
But in other situations, we don't know.
00:18:54
Speaker
So that's another reason why we've got to have this diagnostic and prognostic humility because we are going to be as good as the information that we receive.
00:19:05
Speaker
If we can't be certain of the quality of the information that we're receiving, we've got to have a healthy doubt there, but not dismiss it completely, but just make sure that we don't say, oh, this person had ROSC time, 50 minutes, and that's why they're going to have poor outcomes.
00:19:22
Speaker
So I think that's an important lesson from everything you described, Sergio.
00:19:27
Speaker
And the second piece,
00:19:28
Speaker
Yes, those patients who come in with shockable rhythms do tend to have better outcomes.
00:19:34
Speaker
Those patients who have hypoxic or ischemic, hypoxic anoxic reasons for their arrest, it also makes you wonder how quickly somebody is able to secure their airway for how long they were down, for how long they had exposure of their brains to this hypoxic state before they had a cardiac arrest.
00:19:58
Speaker
So while there isn't a lot of definitive data to suggest, you know, one way or the other, just given that there are all these other factors that do need to be taken account when we're prognosticating, but when we look at Hyperion, for example, and we look at how those patients behaved with TTM down to 33, and you're seeing, okay, there's improvement in outcome, or as compared to TTM2, where not a lot of those patients had, you know,
00:20:27
Speaker
were intra-hospital arrest.
00:20:28
Speaker
They were all outside hospital cardiac arrest patients and Hyperion had intra-hospital cardiac arrest and a lot of our intra-hospital cardiac arrest patients do tend to have non-shockable rhythms or may have hypoxic or anoxic reasons for their cardiac arrest.
00:20:46
Speaker
So keeping that in mind, I think
00:20:50
Speaker
Just interpreting the data with caution, while historically we know that patients who are in shockable rhythms tend to have better neurological outcomes, it doesn't mean that patients who have rhythms that are not shockable or patients who have hypoxic anoxic injury are not going to have a good outcome.
00:21:11
Speaker
Sergio, I'm not being very definitive here, but that's the state of our data.
00:21:17
Speaker
And I think it's important for our listeners and clinicians to understand that there are situations in medicine, which I think are very common, where we can't be definitive.
00:21:27
Speaker
And that humility you talked about, which is really, I think, a primordial quality of scientific inquiry, is very, very important.
00:21:37
Speaker
So we talked about timing.
00:21:39
Speaker
And just to summarize, obviously,
00:21:42
Speaker
making sure that we're timing it appropriately, and we'll talk more as we talk about the different tests is very important, but also a common number that is thrown out there is 72 hours, right?
00:21:52
Speaker
And 72 hours from ROSC is an important timeframe because especially when people first show up to your ICU or first show up to the hospital, it's very difficult to make, I mean, very broad statements because there's a lot of unknowns.
00:22:09
Speaker
But you also mentioned
00:22:11
Speaker
confounding factors.
00:22:12
Speaker
And I would like to maybe dive a little bit deeper into that, Neha, if you could tell us more about confounding factors.
Criteria for Brain Death
00:22:19
Speaker
Absolutely.
00:22:19
Speaker
So confounding factors include, say somebody was already cold because of environmental factors at the time they had their cardiac arrest.
00:22:29
Speaker
So
00:22:31
Speaker
making sure that we don't interpret the lack of brainstem reflexes of somebody's body temperature because of environmental factors was already say 29, 30 degrees and you don't see any brainstem reflexes, then you interpret that as, oh, this person's gonna have a poor outcome.
00:22:46
Speaker
So that's one piece of information.
00:22:50
Speaker
Other confounding factors, things that we do to our patients, whether it's sedatives, whether it's paralytics, whether it's understanding for how long some of these medications are going to linger and the metabolites from these medications, particularly medications like benzodiazepines, Versed, or midazolam, for how long are the metabolites going to linger in somebody who has hepatorenal dysfunction?
00:23:15
Speaker
And some of these patients will have myoclonic seizures or myoclonic status epilepticus or status epilepticus, non-convulsive status epilepticus, and you end up putting them on high-dose Versed or midazolam drips.
00:23:30
Speaker
It's going to take time for those medications to wash out from somebody's system.
00:23:34
Speaker
So we want to be careful in preventing over-interpretation of depressed brainstem reflexes in the context of sedative medications.
00:23:46
Speaker
Want to make sure that you have given enough time for rocuronium to exit somebody's system, particularly if they have end-stage renal disease or AKI and now you're on CRRT.
00:23:57
Speaker
So you're not seeing any movements or any response to pain.
00:24:01
Speaker
That doesn't mean that that patient truly is paralyzed because of their underlying brain injury, but could very well be under the effect of rocuronium.
00:24:12
Speaker
So I think medications having a good understanding of metabolism, working closely with your pharmacists,
00:24:20
Speaker
I think ICU pharmacists are an invaluable resource to us as we manage some very complex patients in our ICUs.
00:24:27
Speaker
So making sure we understand the pharmacokinetics changes in the pharmacodynamics for some of these medications
00:24:34
Speaker
before we interpret what we're seeing on our clinical exam, or even the EEG for that matter.
00:24:39
Speaker
EEG, the findings can be confounded by what you have your patients on.
00:24:46
Speaker
Propofol can induce birth suppression in patients.
00:24:49
Speaker
Midazolam will induce birth suppression, depending upon the doses you're using.
00:24:54
Speaker
So being careful in saying, oh, the EEG is showing a malignant pattern because now this patient is in birth suppression.
00:25:01
Speaker
But guess what?
00:25:02
Speaker
patient is in birth suppression because of the doses of propofol that this patient is on because now they have severe ARDS and you're on high doses of propofol.
00:25:11
Speaker
So I think that is another component.
00:25:14
Speaker
The third kind of confounder would be the different kinds of organ failures that these patients are going to suffer from, particularly hepato-renal.
00:25:25
Speaker
And when we talk about this, this broad, broad term encephalopathy,
00:25:30
Speaker
hepatic encephalopathy, uremic encephalopathy.
00:25:33
Speaker
So is there any other sepsis-associated encephalopathy?
00:25:36
Speaker
Is there any other organ dysfunction that is contributing to worsening encephalopathy?
00:25:45
Speaker
We've all had those patients, right, who come in with a UTI and then they slip into a coma as you're managing their septic shock.
00:25:51
Speaker
So why is that patient who comes in with a normal brain in a coma?
00:25:56
Speaker
They're in a coma because of sepsis-associated encephalopathy.
00:26:00
Speaker
So making sure that we not only look at that primary reason that the patient came to our ICUs with,
00:26:08
Speaker
but understanding that milieu that that primary injury has now created and all the different systemic injuries, all the different hytrogenic concerns that need to be taken into account before interpreting what is happening by way of the clinical exam or on electrophysiological tests.
00:26:29
Speaker
Excellent.
00:26:30
Speaker
Before we go into describing the prognostic test, what I wanted to ask you about is brain death.
00:26:37
Speaker
Because my interpretation has always been that it's not as common, but brain death is brain death no matter when it shows up, if it's diagnosed appropriately.
00:26:46
Speaker
Could you comment on that, Neha?
00:26:48
Speaker
Absolutely.
Process of Declaring Brain Death
00:26:49
Speaker
And, Sergio, I agree with you that a lot of states in the United States and several countries in the world
00:26:57
Speaker
do agree with the statement that brain death is the equivalent of death and being absolutely sure that a patient has become brain dead before we declare them because that truly, truly is the difference between life and death.
00:27:13
Speaker
So every state, state's Department of Health has guidance, I can speak for United States, has guidance on
00:27:21
Speaker
how to, what are the criteria before you declare somebody brain dead?
00:27:26
Speaker
And making sure that you're aware of your Department of Health policy for the state that you practice in or states that you practice in, as well as the local hospital health system policies, and making sure that your local hospital health system policies are in line with your state's Department of Health policies on how to suspect and diagnose that somebody has brain death.
00:27:51
Speaker
In terms of the clinical exam, all those things, and this is actually a nice rip from the confounding factors that we were talking about.
00:27:57
Speaker
So most departments of health in the United States will suggest that you, or will enlist, what are some of those confounders that you have to be very careful about before you proceed with even that clinical examination and saying that all the absence of different brainstem reflexes that you find on your clinical exam
00:28:20
Speaker
is not because of any confounders.
00:28:23
Speaker
And other confounders that we have to be careful about, whether somebody has profound electrolyte abnormalities, whether it's hypoglycemia, hypoglycemia, acidosis, different kinds of electrolyte abnormalities.
00:28:37
Speaker
And some of these confounders can depress different kinds of brainstem reflexes.
00:28:42
Speaker
So we have to be sure that the exam that we're seeing is not because of those kinds of confounders.
00:28:49
Speaker
And the number one thing is you have to have structural proof of severe acute brain injury because if you don't have proof of that, then you have to be very careful before you proceed with doing your clinical examination.
00:29:05
Speaker
So if somebody has a massive intracerebral hemorrhage with herniation or somebody with massive global cerebral edema after surgery,
00:29:15
Speaker
a cardiac arrest.
00:29:16
Speaker
So you have that structural proof that somebody has sustained severe acute brain injury.
00:29:22
Speaker
Then the next step is, has this person progressed to brain death or not?
00:29:26
Speaker
So making sure that none of those confounders exist.
00:29:29
Speaker
In New York State, for example, the body temperature that somebody needs to be at before we proceed with clinical examination is 36 or higher, 36 degrees Celsius or higher.
00:29:40
Speaker
So after that, you proceed with checking for the presence or absence of different brainstem reflexes and then performing a confirmatory test.
00:29:50
Speaker
And in this, for New York State, the confirmatory test is apnea testing.
00:29:55
Speaker
And for whatever reason, if you can't perform an apnea test, for example, somebody who has severe ARDS or somebody who's in profound shock and you're on multiple pressors, et cetera.
00:30:04
Speaker
So you can't proceed with performing an apnea test.
00:30:06
Speaker
then you can perform some ancillary tests to confirm the diagnosis of brain death.
00:30:14
Speaker
Excellent.
00:30:15
Speaker
And also I wanted to, obviously, like you said, there's a lot of criteria related to determining death by neurologic criteria.
00:30:22
Speaker
There's also, like you said, local state health requirements, which obviously everybody should be aware of.
00:30:29
Speaker
And we'll link the show notes to a podcast we had with Dr. David Greer talking about
00:30:35
Speaker
that as well.
00:30:36
Speaker
But within the context of a cardiac arrest, my question really is, Deha, we talked about 72 hours, but if you meet all the criteria you mentioned before that window, it means the patient is brain dead.
00:30:50
Speaker
Is that a correct interpretation?
00:30:53
Speaker
What I would recommend in that situation is repeating neuroimaging because if somebody truly has lost all of their reflexes,
00:31:05
Speaker
making sure that you have repeat imaging to confirm that evolution.
00:31:09
Speaker
If they didn't get a day zero CT head and some places may not have the ability to do that kind of day zero CT head, but my recommendation would be always get that day zero CT head because sometimes you will pick up the underlying cause of the arrest on that day zero CT head.
00:31:25
Speaker
Example,
00:31:26
Speaker
would be a severe aneurysmal seborrachnoid hemorrhage.
00:31:32
Speaker
Or you may see that somebody had a cardiac arrest and was found down, and now they also have a massive subdural hematoma.
00:31:40
Speaker
So you can both be able to identify a potential cause for the cardiac arrest, as well as some unintended or difficult to otherwise pick up consequence of the cardiac arrest
00:31:55
Speaker
for example, from this fall post-cardiac arrest when somebody's found down.
00:31:59
Speaker
And the third thing is having, if you see global cerebral edema on that day zero CT head, then the likelihood that somebody's going to have a good outcome is low.
00:32:11
Speaker
However, we often don't have a comparison CT head from their pre-morbid state.
00:32:19
Speaker
Or if we end up seeing some of these patients
00:32:22
Speaker
come to the same hospitals or health systems and you may have access to their prior records and compare that day zero CT head before you interpret the appearance of loss of gray-white junction or sulcal effacement as global cerebral edema.
00:32:38
Speaker
So in that kind of patient, if within 72 hours you're seeing and barring all of those other confounders that we spoke about, if you see that they're
00:32:50
Speaker
showing a loss of all their brainstem reflexes, then my recommendation would be proceed with a repeat CT head to look at the evolution.
00:32:57
Speaker
And sometimes you will see this clear evolution where patients have developed profound global cerebral edema and this kind of pattern of a pseudo-sabarachnoid hemorrhage, or you begin to see absolutely no gray-white differentiation.
00:33:13
Speaker
So if that is happening, then I think you could then proceed with
00:33:20
Speaker
brain death declaration before 72 hours.
00:33:22
Speaker
But that situation is so, so rare and I'm usually quite cautious in proceeding down that pathway.
00:33:32
Speaker
Perfect.
00:33:34
Speaker
So let's dive into the prognostic tests that constitute multimodal neuro prognostication.
Role of Physical Exams in Prognostication
00:33:41
Speaker
Then maybe we could, after we go over those, we could talk about some common pitfalls and then close by
00:33:47
Speaker
putting it all together and presenting a framework of what you do in your regular practice in Mount Sinai.
00:33:55
Speaker
So why don't we start with the physical exam?
00:33:59
Speaker
So the physical exam for all, for all brain injuries, a physical exam is super, super important.
00:34:04
Speaker
And in these patients, before instituting TTM, getting your first physical exam before the institution of TTM, I think that will be, that is quite important.
00:34:15
Speaker
If you see absolutely no presence of brainstem reflexes, including absence of pupillary reflex, corneal reflex, no motor response, you can add that point to that story that you're building for prognostication and it's suggestive of there is a potential for poor prognosis.
00:34:33
Speaker
So get that exam before TTM, but that exam itself cannot guide what is going to happen next to the patient.
00:34:43
Speaker
So it's just one more data point that you can add to that story, but don't put too much weight on what you're seeing.
00:34:52
Speaker
If there is absence of different reflexes, it doesn't mean that this person is absolutely committed to a poor prognosis, but maybe there is a higher possibility of having poor prognosis.
00:35:04
Speaker
Then doing an exam serially
00:35:07
Speaker
while you're instituting TTM, looking for whether somebody is developing myoclonic jerks or not.
00:35:15
Speaker
And particularly the moment when TTM is being instituted irrespective of the temperature target, that period when somebody is being actively cooled and actively being re-warmed, those are vulnerable periods.
00:35:27
Speaker
So seeing what is happening both clinically as well as on EEG.
00:35:33
Speaker
So my suggestion always is, you know, when you're instituting TTM,
00:35:36
Speaker
get these patients connected to EEG.
00:35:38
Speaker
Myoclonic jerks, whether they are subcortical myoclonic jerks, so these are not seizures, they are subcortical myoclonic jerks,
00:35:48
Speaker
or cortical myoclonic jerks, which are seizures, you are going to need to look at what happens to the EEG when somebody has myoclonic jerks.
00:35:57
Speaker
So that's another good reason to have somebody connected to EEG because a lot of patients will develop myoclonic jerks in the first 24 to 48 hours post cardiac arrest.
00:36:09
Speaker
With respect to the
00:36:12
Speaker
how we test different reflexes.
00:36:15
Speaker
So pupillary reflex, doing the conventional sort of naked eye exam of the pupils versus there are some studies now that also look at pupilometry or near infrared pupilometry exams.
00:36:30
Speaker
to quantify the pupillary reactivity.
00:36:33
Speaker
So if you have pupillometers available, I would recommend, you know, use pupillometers.
00:36:37
Speaker
You can do them Q1 hours while somebody is undergoing TTM.
00:36:43
Speaker
But if you don't, even that naked eye pupillary exam is good enough, although there is interrater variability.
00:36:50
Speaker
So when you say some of these pupils are not reactive, be absolutely sure that they are not reactive.
00:36:56
Speaker
So those are some things on the clinical exam that should be documented.
00:37:01
Speaker
Some things on the clinical exam that will give you an idea in building that story for good prognosis would be the presence or the re-emergence of certain brainstem reflexes, whether it's the pupils, whether it's corneals, whether it's cough, gag, say these reflexes were absent and they come back, or that they're present right from day zero onwards.
00:37:24
Speaker
On the motor exam, if you're beginning to see some motor response, particularly withdrawal to pain, localization to pain, those are also signs of good prognosis.
00:37:36
Speaker
And I hope just keeping those kinds of things in mind, but again, checking what drips is my patient on?
00:37:46
Speaker
and how much can I interpret what I'm seeing?
00:37:49
Speaker
Do I have the opportunity or the ability to do an exam of sedation or not?
00:37:54
Speaker
Because sometimes it may just not be safe.
00:37:56
Speaker
So we should just be careful in the interpretation of these different physical exam findings.
00:38:08
Speaker
Sergio, should I talk about other tests or any questions about the physical exam?
00:38:12
Speaker
So let me ask you about the physical exam.
00:38:15
Speaker
Just one more thing.
00:38:16
Speaker
In terms of the pupillary reflex, the corneal reflex and motor response are kind of like very commonly obviously quoted because they were very important in the original PLUM studies.
00:38:27
Speaker
Are there any timeframes that you wanna highlight as being of significance?
00:38:34
Speaker
There's actually an excellent review paper and there are two review papers that Sandroni and Sandroni et al.
00:38:40
Speaker
have written.
00:38:41
Speaker
One on how to,
00:38:44
Speaker
how to predict good prognosis and how to predict poor prognosis.
00:38:50
Speaker
The poor prognosis paper is from 2020 and the good prognosis paper is from 2022.
00:38:57
Speaker
Both of them were published in intensive care medicine.
00:38:59
Speaker
The authors have done an excellent job of using the, they've done a lot of work
00:39:06
Speaker
not only looked at the PICO framework, but they also specifically look at time and repeated measures for different things on the physical exam than the other tests, including biomarkers, imaging, EEG.
00:39:19
Speaker
So what do you find in the first 24 hours, 72 hours, so on and so forth.
00:39:23
Speaker
So they've done a very good job of summarizing the true positive, false positive, as well as sensitivity, specificity for all of these different signs.
00:39:36
Speaker
So I think the repeated measures, there is definitely data on all these different tests and different studies have studied it slightly differently, but Sandroni et al have done a good job of summarizing all of that.
00:39:53
Speaker
I think one of the papers actually has like 50 tables.
00:39:56
Speaker
They've included everything with respect to all these different time points.
00:40:00
Speaker
So for example, for pupils, if the pupillary response
00:40:05
Speaker
is absent at day zero or within 24 hours, then it's also absent at 72 hours, then it is, you know, it's more specific for a poor prognosis.
00:40:17
Speaker
But the problem is it's not a very sensitive sign.
00:40:20
Speaker
So I think we just have to be careful.
00:40:22
Speaker
The message I would like to share is repeated assessments are needed for each of those different things on the physical exam.
00:40:30
Speaker
There are studies that have looked at
00:40:33
Speaker
Each of those different signs and reflexes that we spoke about, as well as the motor exam and testing for these at different time points with TTM, without TTM, most of the studies that were included in the Sandroni papers were with TTM.
00:40:53
Speaker
So I think it's totally worthwhile.
00:40:55
Speaker
If you have a question about a particular reflex or, you know, the interpretation of or the sensitivity specificity of each of these different things on the exam, these would be two good papers to keep handy.
00:41:08
Speaker
And we'll reference them in the show notes.
00:41:11
Speaker
Thanks, Neha.
00:41:12
Speaker
So let's talk about biochemical tests real quickly.
00:41:15
Speaker
These are unfortunately, I think, are not as available in terms of timely fashion in many places that I've seen people practice.
00:41:22
Speaker
But I'm sure that there's some data and I just want to hear how you utilize them if you do.
Neuron-Specific Enolase Testing Challenges
00:41:28
Speaker
Sergio, you are absolutely right.
00:41:30
Speaker
Getting access to NSE, neuron-specific enolays, in a timely fashion and the results coming back in time.
00:41:37
Speaker
For Mount Sinai, for example, when we send off NSE, we don't get our first result back within the first three days.
00:41:45
Speaker
Like it takes time for neuron-specific enolays to come back.
00:41:49
Speaker
And there are lots of papers that have looked at neuron-specific inolates and, you know, different kinds of cutoffs.
00:41:55
Speaker
I always am cautious about using any one particular cutoff.
00:41:59
Speaker
I look at the trends.
00:42:01
Speaker
That's why I'll ask our teams to send three samples on day one, day two, and day three.
00:42:10
Speaker
And then, of course, it will take some time for this to result.
00:42:13
Speaker
S-beta 100 is another one of those biomarkers.
00:42:17
Speaker
We don't have access to it.
00:42:19
Speaker
At our center, again, access to these biomarkers
00:42:24
Speaker
using them as another data point as part of multimodal prognosis.
00:42:29
Speaker
I think it's useful when you look at the sensitivity, specificity of these biomarkers put into the right context with multimodal prognosis.
00:42:41
Speaker
Micro RNA measurements have also been studied.
00:42:44
Speaker
There's a bunch of different biomarkers that have been studied.
00:42:47
Speaker
Neuron-specific enolase just happens to be the biomarker that we have the most data on.
00:42:52
Speaker
but caution is advised.
00:42:54
Speaker
Don't look at a single cutoff and say poor prognosis.
00:42:59
Speaker
The trend in these values is important and putting it in the context of multimodal prognostication is important because although the name of the biomarker is neuron-specific enolase, it's a very nonspecific marker of neurological injury.
00:43:16
Speaker
Perfect.
00:43:16
Speaker
So I guess that the summary there really is that if you have it available,
00:43:22
Speaker
use it with caution, but it definitely is another piece to that multimodal puzzle.
00:43:28
Speaker
And if done serially, can provide information that has been validated as being associated with certain prognosis.
00:43:34
Speaker
So I think that's fair.
00:43:36
Speaker
And like you said, I don't think that it's widely available, but there are obviously a lot of hospitals who have access to it, even if it takes a day or two to come back.
00:43:47
Speaker
Excellent.
00:43:49
Speaker
The next, I guess, group of prognostic tests include, and I don't know if this is the right term, but electrical tests.
EEG and SSEP in Prognosis
00:43:57
Speaker
And I would like to start with EEG, and then maybe you can talk about sensory evoked potentials, SACP.
00:44:07
Speaker
Absolutely.
00:44:07
Speaker
So electrophysiology, I'm a huge fan of electrophysiological tests, particularly EEG.
00:44:12
Speaker
And I am not a critical care EEG specialist, but I do believe that if we had the ability to use EEG and connect people to EEG monitoring, just like we connect them to EKG, just that access, the ease of
00:44:29
Speaker
and experts to be able to interpret those tests, we would be using EEG so much more widely.
00:44:35
Speaker
The utility of continuous EEG monitoring is tremendous in patients with different kinds of acute brain injuries, particularly in patients post-cardiac arrest.
00:44:44
Speaker
So there are several studies that have described different patterns on EEG that can both tell us whether somebody's going to have a poor prognosis versus somebody who's going to have a good prognosis.
00:44:58
Speaker
So there are some patterns that are recognized as malignant patterns.
00:45:02
Speaker
And what are some of those patterns?
00:45:04
Speaker
So spontaneous birth suppression.
00:45:07
Speaker
Spontaneous birth suppression means that it is not because you have them on propofol or midazolam or any other sedatives that can potentially cause birth suppression, but the underlying brain is injured so severely that it's gone into spontaneous birth suppression.
00:45:27
Speaker
having different kinds of ictal interictal patterns with non-convulsive status that meet criteria for non-convulsive status epilepticus.
00:45:37
Speaker
So some of these periodic patterns can, when they are 2.5 hertz or higher, then they meet the criteria for non-convulsive status epilepticus.
00:45:48
Speaker
Again, caution is advice that
00:45:51
Speaker
All patients who develop myoclonic status epilepticus are not deemed to have a poor prognosis.
00:45:57
Speaker
There are studies that show us that if we are aggressive in treating the myoclonic status epilepticus, patients may have a good outcome.
00:46:05
Speaker
So before you interpret the EEG as having a malignant pattern, a fully suppressed background without any reactivity in the background, without being on any other confounding medications, et cetera,
00:46:21
Speaker
those would be regarded as patterns suggestive of a poor outcome.
00:46:26
Speaker
And then what can tell us that somebody is going to have a good outcome?
00:46:31
Speaker
Reactivity on EEG.
00:46:34
Speaker
It essentially shows some changes when you stimulate a patient either by way of voice or by touch,
00:46:41
Speaker
and you're seeing some changes in EEG.
00:46:43
Speaker
So that's reactivity, which is suggestive of a good outcome.
00:46:47
Speaker
Or you begin to see the background rhythm emerging, or somebody has sleep-wake cycles.
00:46:54
Speaker
So those are things that are suggestive of good outcomes.
00:46:57
Speaker
So EEG is a very powerful, non-invasive neurophysiological modality that can help both diagnose as well as prognosticate post-cardiac arrest.
00:47:11
Speaker
The problem with EEG, of course, it is affected by so many things, including the medications that we have patients on.
00:47:16
Speaker
So we have to be careful when we interpret EEG, as opposed to SSEP.
00:47:20
Speaker
So with SSEP, somatosensory evoked potentials, I'll just share, it is hard.
00:47:25
Speaker
It is hard for us to get SSEPs at our centers.
00:47:29
Speaker
At Mount Sinai Hospital, for example, it's difficult for us to get SSEPs outside of intraoperative monitoring.
00:47:36
Speaker
They're using it as part of intraoperative monitoring all the time, but getting it in the ICU is a little bit operationally harder for us.
00:47:44
Speaker
So we don't end up using as much SSEP as some other centers do.
00:47:51
Speaker
SSEPs should be performed after re-warming because they can be affected by lower temperatures.
00:47:59
Speaker
However, as compared to EEG, SSEP tends to not get as affected by sedative medications.
00:48:06
Speaker
Both of these tests, the electrophysiological tests, can suffer from interference with different devices, even infusion pumps, etc., ventilators that we use in the ICU.
00:48:16
Speaker
So just working closely with your electrophysiology teams to remove some of those, there are ways of removing some of those interfering signals before the interpretation of the studies.
00:48:33
Speaker
So they're both very helpful.
00:48:36
Speaker
SSEPs tend to be fairly specific and accurate if you have absence of the N20 response
00:48:46
Speaker
which is that high up cortical response of the somatosensory pathway.
00:48:52
Speaker
And for EEG, again, there's a lot of these different patterns have good sensitivity.
00:48:58
Speaker
They are not as specific, but good sensitivity.
00:49:01
Speaker
Additional question with the EEG, Neha, is it is something that I've always found confuses people.
00:49:12
Speaker
the presence of generalized status myoclonus has a very different significance than the patient has myoclonic jerks.
00:49:21
Speaker
Could you maybe clarify that for us?
00:49:25
Speaker
So, you know, when we read studies, I think, I would say before 2013 that describe myoclonic status epilepticus and patients having a poor outcome,
00:49:38
Speaker
I think we've touched upon this theme in a lot of our conversation, the variability.
00:49:45
Speaker
So all myoclonists is not created the same.
00:49:48
Speaker
When people were describing myoclonic status epilepticus or myoclonic jerks in literature, everybody wasn't speaking the same language.
00:49:56
Speaker
Now that EEG utilization has become a little more prevalent, it's obviously not as widely available as the
00:50:05
Speaker
would like it to be, but the fact that it is available more widely, looking for whether the myoclonic jerks that you're seeing are cortical myoclonis or subcortical myoclonic jerks.
00:50:19
Speaker
Subcortical myoclonic jerks, one kind of subcortical myoclonic jerk will be Lance Adams myoclonis.
00:50:26
Speaker
Those patients are going to have a good prognosis
00:50:30
Speaker
that is suppressible by some of our anti-seizure medications as well.
00:50:33
Speaker
Although this is not necessarily a seizure, it's subcortical myoclonus, but you can still suppress it with some anti-seizure medications.
00:50:40
Speaker
And if there is any doubt, is this cortical or is this subcortical myoclonus?
00:50:45
Speaker
So one possible way to distinguish between the two, at the bedside, if you have somebody connected to EEG monitoring, you give them a benzotrial.
00:50:55
Speaker
By a benzotrial, I mean a low-dose benzodiazepine.
00:50:59
Speaker
So you could use, for example, one or two milligrams of midazolam and see what happens to their EEG as well as to their myoclonins.
00:51:08
Speaker
You may not be able to see a
00:51:11
Speaker
One possibility is nothing happens, there's no change.
00:51:14
Speaker
Another possibility is that you're temporarily able to suppress the myoclonic jerks and you don't see any artifact on the EEG when a patient begins to have myoclonic jerks again.
00:51:26
Speaker
Or you begin to see time-locked changes in the EEG along with that myoclonic jerk which tells you that this is cortical myoclonus.
00:51:35
Speaker
So myoclonic seizures
00:51:37
Speaker
Subcortical myoclonis, both of these can be controlled with the same medications.
00:51:42
Speaker
You can use, for example, valproic acid if your patient does not have shock liver or any acute liver injury post cardiac arrest.
00:51:50
Speaker
Valproic acid is a good medication.
00:51:52
Speaker
Leboturacetam can help in these patients.
00:51:55
Speaker
If you're able to very easily control whether it's subcortical or cortical myoclonis with anti-seizure medications, then
00:52:04
Speaker
Another hint towards maybe this is going to be a patient who's going to have a good outcome.
00:52:11
Speaker
As opposed to patients with myoclonic status epilepticus, again, my read of the literature is to be aggressive in treating it if there are other data points that are telling you that there is a possibility for a good neurological outcome.
00:52:29
Speaker
So if we don't treat myoclonic status epilepticus just like we treat other forms of convulsive status epilepticus aggressively, then it becomes part of a self-fulfilling prophecy.
00:52:44
Speaker
So I hope, Sergio, that clarifies myoclonic seizures, subcortical myoclonus, and myoclonic status epilepticus.
00:52:52
Speaker
Absolutely.
00:52:53
Speaker
And I think it also highlights the importance of really applying EEG to these patients.
00:52:58
Speaker
And like you said, I think the utilization of EEG is growing throughout the country, but obviously I'm sure it's much higher in a dedicated neuro ICU than a general ICU.
00:53:10
Speaker
But as clinicians, I think that we should just be thinking at a very practical level that we have a brain injured patient, we're monitoring their heart rate continuously, we're monitoring sometimes their blood pressure continuously, we're monitoring their lungs continuously,
00:53:25
Speaker
Why shouldn't we have something to monitor their brain continuously?
00:53:28
Speaker
Whatever is available, we should be pushing for that.
00:53:31
Speaker
Very well said.
00:53:32
Speaker
Yep.
00:53:34
Speaker
So the last component of these prognostic tests is imaging, brain imaging, which I think really means for most people, CT scans or MRIs.
CT and MRI Imaging
00:53:44
Speaker
And you already mentioned earlier in the conversation the value of getting a CT scan upfront to understand possible causes.
00:53:53
Speaker
but could you give us a little bit more detail on how you utilize and what the evidence supports for the use of brain imaging and neuroprognostication itself?
00:54:03
Speaker
Sure thing.
00:54:04
Speaker
So the DayZero CT head, you know, we discussed earlier, it may give you an idea of what the underlying etiology for the cardiac arrest is.
00:54:13
Speaker
If you're seeing global cerebral edema or loss of gray-white
00:54:17
Speaker
differentiation is something called as gray-white ratios which can be calculated if you begin to see that on your first CT head, the CT head that is done within the first 24 hours, then it's an important data point to capture.
00:54:33
Speaker
Also to be able to compare the evolution of injury from day zero to say 72 or more hours when you're going to begin to really
00:54:45
Speaker
put together that puzzle of neuro prognostication.
00:54:47
Speaker
So if you don't have a particularly younger brains, the brains are going to look so full where we're used to seeing CT scans in our elderly patients where there is some physiological, you know, atrophy that you're already seeing.
00:55:00
Speaker
So identifying loss of gray by differentiation on those CTs is a little bit easier as compared to identifying loss of gray by differentiation on younger people's CT heads because their brains are really full.
00:55:12
Speaker
So that isn't really
00:55:15
Speaker
a whole lot of swelling or hypoxic ischemic injury that is going to cause loss of gray-white differentiation.
00:55:25
Speaker
So you have to be careful when you're interpreting CT heads in younger patients as compared to elderly patients.
00:55:30
Speaker
So that's why I always try to get, so you're going back to your point of repeated measures.
00:55:35
Speaker
That's why I always advocate for getting a CT head within the first 24 hours of cardiac arrest.
00:55:43
Speaker
as well as then we can talk about whether repeating a CT head at 72 hours or greater versus doing an MRI.
00:55:52
Speaker
So with respect to getting an MRI in these patients, of course, what else is going on with these patients?
00:55:59
Speaker
If somebody's on mechanical circulatory support or say you had to put this patient on ECMO, you're obviously not going to be able to get an MRI on those patients.
00:56:10
Speaker
So then repeating a CT head in those patients would be reasonable.
00:56:14
Speaker
And if you had a
00:56:16
Speaker
and this becomes especially helpful if you already had another CT head to compare the two with, unless there are dramatic findings.
00:56:26
Speaker
When we look at this gray-white ratio, it's measured at three levels, and there are certain areas in the brain that are more vulnerable to hypoxic ischemic injury, and whether it's the
00:56:42
Speaker
the cortex itself, basal ganglia, within the cerebellum, there are specific areas that are vulnerable, hippocampi, et cetera.
00:56:51
Speaker
So you'll be able to identify some of that on the CT head.
00:56:55
Speaker
Now on MRI,
00:56:56
Speaker
On MRI, there are obviously different sequences.
00:56:59
Speaker
When I'm talking to patients and families, I'll often say that on MRI, we look at different sequences.
00:57:05
Speaker
You can think of these sequences as filters on Instagram, right?
00:57:08
Speaker
These different filters, which give us a better resolution of specific things on the picture that we're trying to obtain.
00:57:20
Speaker
When we look at these MRI sequences, there are two MRI sequences, the DWI, the diffusion weighted imaging, and the ADC, the apparent diffusion coefficient.
00:57:30
Speaker
So the ADC imaging, there are studies that have looked at quantifying the ADC burden of injury and correlating that with outcome.
00:57:42
Speaker
One word of caution when you look at imaging studies, in patients who have anoxic brain injury or predominantly there was a hypoxic or anoxic cause of arrest, the initial imaging may be completely normal.
00:57:56
Speaker
And unless you did repeated imaging, you may not be able to see any ablution of injury.
00:58:01
Speaker
So one good rule would be if you don't see any diffusion-weighted
00:58:07
Speaker
on DWI or ADC, you don't see any injury there on your first imaging and then you do a subsequent image by day five or day seven, then you could say, okay, then there is a possibility of a good outcome.
00:58:26
Speaker
But if you begin to see evolution of injury,
00:58:29
Speaker
then you know that there is at least some areas of the brain that are involved.
00:58:34
Speaker
And quantifying that injury, whether it's mild, moderate, severe, it depends upon how many areas are involved.
00:58:41
Speaker
But again, imaging should not be utilized in isolation of everything else.
00:58:47
Speaker
It is also just one more data point
00:58:51
Speaker
for that multimodal prognostication.
00:58:54
Speaker
There are very few things on imaging, for example, this massive global cerebral edema or complete loss of gray-white junction or an MRI, you're just seeing a very high burden.
00:59:05
Speaker
There's diffuse cortical ribbing and basal ganglia diffusion restriction and cerebellar diffusion restriction, so on and so forth, that tell us, okay, this person has severe HIB or severe HIE.
00:59:18
Speaker
Excellent.
00:59:18
Speaker
And it's also interesting that from a just a social perspective, imaging is usually a big deal for families because I think it's something objective that people can understand and look at.
00:59:32
Speaker
And they're always asking, are you going to repeat the CAT scan?
00:59:35
Speaker
Are you going to get an MRI?
00:59:37
Speaker
Because somehow they feel that that's going to give a definitive answer.
00:59:40
Speaker
And I think it's important also for us to, from the get go, explain
00:59:44
Speaker
this process really evolves and that there's not one definitive test and that it's the combination of those with time and what we see in terms of evolution that ultimately will give us the best available information.
Time in Multimodal Prognostication
00:59:56
Speaker
You're absolutely right and in that conversation letting them know that time is also as part of multimodal prognostication I almost feel like time should be thought of as one more marker of prognosis
01:00:11
Speaker
because these repeated measures are as important as any of these individual tests.
01:00:18
Speaker
I almost feel very lucky sometimes as a neuro intensivist when I talk to patients and families and particularly when I'm having these family meetings, because a picture speaks a thousand words, right?
01:00:28
Speaker
So just having that scan and showing the scan to patients and families, or most of the times these patients cannot participate in decision making.
01:00:37
Speaker
We're showing it, just being able to really
01:00:40
Speaker
give them an opportunity to wrap their heads around what has happened, it is very helpful.
01:00:45
Speaker
So I do hear you, you know, I know where our patients and families are coming from and they're asking for what, can I see what this injury looks like?
01:00:57
Speaker
Absolutely.
01:00:58
Speaker
Are there any common pitfalls that we should avoid?
01:01:03
Speaker
One is avoid self-fulfilling prophecies.
01:01:06
Speaker
Keep yourself in check, having that diagnostic and prognostic humility.
01:01:11
Speaker
being very intentional about staying up to date with what is the current guidance in our field.
01:01:18
Speaker
And it's very hard.
01:01:19
Speaker
It's very, very hard as intensivists to keep up with all of the different literature, particularly subspecialty literature.
01:01:25
Speaker
So my usual approach to that is at least looking at the guidelines from major medical societies.
01:01:32
Speaker
And if you wanted to do a deep dive into one or two recommendations or something that you're experiencing at the bedside,
01:01:40
Speaker
with the patient, then just go back to the source literature for that recommendation from that guideline statement.
01:01:46
Speaker
Another key thing to keep in mind, our guidelines are going to stay behind the most current literature.
01:01:56
Speaker
So if there is a particular clinical question, and if you see a lot of patients post cardiac arrest in your practice, then periodically,
01:02:06
Speaker
setting certain alerts for whether it's via Google Scholar or PubMed, just setting an alert to get those most recent studies or randomized controlled clinical trials directly to your inbox so you are aware and you can then decide for yourself whether you're going to change your clinical practice or not.
01:02:26
Speaker
So I think that lifelong learning
01:02:28
Speaker
is an important piece to add to everything that we have discussed so far.
01:02:33
Speaker
It's true about, I feel like it's true about all of life, but specifically as intensivists, we have to be very careful.
01:02:41
Speaker
We cannot be dogmatic and making sure we have the responsibility to guide so many people in making decisions about what the next course of
01:02:56
Speaker
action or what that journey towards recovery or towards withdrawal of life-sustaining therapies is going to look like.
01:03:02
Speaker
So I think it's a very important position of responsibility.
01:03:07
Speaker
So making sure that we understand.
01:03:10
Speaker
And then misinterpretation of studies.
01:03:14
Speaker
I think, you know, TTM2 in my mind is a good example of how when
01:03:22
Speaker
when somebody is already skeptical about TTM, when they look at TTM2, their interpretation may be, oh, TTM2 is a trial of, you know, now we don't need to do anything for these patients with respect to their temperature control.
01:03:36
Speaker
But that is not what that study is telling us.
01:03:38
Speaker
What that study is telling us is a specific temperature maybe may not matter as much for a specific type of patient population, but how do we customize
01:03:50
Speaker
the results of specific trials because trial populations are not going to, everything that we see in clinical trials is not going to translate to that patient in front of us.
01:04:01
Speaker
But how do we customize our practice for that patient in front of us?
01:04:06
Speaker
And there is some good suggestion on how we can potentially
01:04:12
Speaker
choose different targets, choose different CO2 goals or blood pressure goals for patients post cardiac arrest, depending upon our estimate of how severe their underlying neurological injury may be.
01:04:25
Speaker
So I think customizing our approach, so lifelong learning, making sure we're aware of source literature and guidelines in taking care of these patients and then customizing and applying that at the bedside
01:04:40
Speaker
being aware of all the different confounders that can affect clinical exam, biomarkers, electrophysiological tests.
01:04:54
Speaker
As long as we're aware and we take steps to not over interpret the presence or absence of certain things and putting that in the context of the big picture, that shared decision making.
01:05:08
Speaker
different models of care are practiced in different parts of the world.
01:05:12
Speaker
Just being aware of what kind of model are you a part of?
01:05:17
Speaker
Is it a more paternalistic care model?
01:05:19
Speaker
Is it a more shared decision-making model?
01:05:22
Speaker
So trying to elicit what would be in line with somebody's goals, values, and wishes, and would they be okay with that uncertainty that you're sharing with the family?
01:05:32
Speaker
Because neurological recovery can take weeks to months to even years
01:05:36
Speaker
In cardiac arrest patients, recovery has been described at six months and even up to a year.
01:05:41
Speaker
So then is it, is it, would this person behind the patient for whom you're helping guide make some of these decisions, be okay going to a long-term facility with a trick and peg and waiting to see what happens.
01:05:58
Speaker
So shared decision-making and upholding those principles and trying to elicit what is going to be in line with somebody's goals, values, and wishes.
01:06:06
Speaker
Excellent.
01:06:07
Speaker
And I think that ultimately, if we had to summarize three very important take home messages that I heard over and over again, Nihal, are number one is humility.
01:06:19
Speaker
And I always believe that excellence in clinical practice is more about having the right questions than having answers.
01:06:26
Speaker
So be very humble in terms of what we're trying to determine.
01:06:30
Speaker
Number two is the multimodal approach, right?
01:06:32
Speaker
There's not one test that gives you all the answers.
01:06:36
Speaker
And number three, like you mentioned, time, which is really not only the serial nature of our evaluations, but also understanding that what you see at the first 24 hours might not have the same significance of what you see 72 hours and beyond.
01:06:53
Speaker
And I think that when you put all that together, it's upon our teams to really figure out what they have available at their institutions and to try to set kind of a standard
01:07:05
Speaker
this is how we do it over and over again so that we can learn how to do it well but also try to provide the best available information for our families and for our patients and their families so we can make the right decisions absolutely sergio being consistent with all this uncertainty the least that we can do is be consistent and then re-evaluate our approach in light of new emerging data so that every time we make a decision
01:07:30
Speaker
for a particular kind of therapy or for continuing care or withdrawal of life-sustaining therapies.
01:07:38
Speaker
We're doing it with the best possible knowledge we have at this moment in time.
01:07:43
Speaker
So at the end of the day, we have done our very best to look for the right answer.
01:07:49
Speaker
Excellent.
01:07:50
Speaker
So we would like to close a podcast, Neha, with Tradition and Critical Matters, which is asking our
01:07:56
Speaker
guests to share a little bit of their wisdom outside of the clinical topic we discussed.
01:08:00
Speaker
Would that be okay?
01:08:02
Speaker
Absolutely.
01:08:02
Speaker
Would love to.
Book Recommendations by Dr. Tangayak
01:08:04
Speaker
So the first question is regarding books.
01:08:07
Speaker
Is there a book or any books that have influenced you significantly or that you have gifted often to other people?
01:08:15
Speaker
How to Win Friends and Influence People by Dale Carnegie.
01:08:18
Speaker
I absolutely love the book.
01:08:19
Speaker
It was written, you know, years and years ago, but so many of those lessons are very applicable to how we
01:08:26
Speaker
lead ourselves and how we live our lives.
01:08:29
Speaker
Go ahead.
01:08:31
Speaker
Sorry, go ahead.
01:08:33
Speaker
And Adam Grant's Think Again, because that whole theme of humility, re-evaluating, you come up with one answer, but when there's new data shown to you, just think again.
01:08:45
Speaker
So I thought the book did a marvelous job of, you know, just highlighting that.
01:08:50
Speaker
And Sergio, you said it beautifully about how
01:08:54
Speaker
you know, only fools are going to be dogmatic and so sure about what they're doing.
01:08:58
Speaker
So Adam Grant's Think Again is a wonderful book.
01:09:01
Speaker
And then Brené Brown's Dare to Lead.
01:09:04
Speaker
I love all these three books.
01:09:06
Speaker
Excellent.
01:09:06
Speaker
And they're all, I think, highly recommended.
01:09:09
Speaker
And it just also, one of the reasons why I always like to ask this question is because there is tremendous value in these three books, which are outside of medicine and being a better clinician.
01:09:21
Speaker
And I would definitely encourage our listeners to check them out.
01:09:25
Speaker
And especially, I think all of them are phenomenal, but when you talk about Adam Grant's book, which is the, of all the three, is the newest one.
01:09:34
Speaker
It's interesting, like he talks about thinking like a scientist, right?
01:09:38
Speaker
And what that made me think, Nihai, is that we all believe we're scientists, yet we rarely behave like such.
01:09:45
Speaker
True.
01:09:49
Speaker
So the second question is about beliefs.
01:09:52
Speaker
Is there something that you believe to be true in medicine or in life that most other people don't believe or at least don't act like they believe?
01:10:00
Speaker
I think everything happens for a reason and that everything is interconnected and that the very essence of life is trying to strike the right balance.
01:10:11
Speaker
When I think of homeostasis in the ICU, everything that we try to do, whether it's hyper or hypoglycemia, like they're both bad, but euglycemia is good.
01:10:20
Speaker
Hypo, hyponatremia, both bad.
01:10:22
Speaker
You know, fluid, fluid status, volume, feed, everything.
01:10:26
Speaker
I almost feel like everything in life is about trying to strike the right balance.
01:10:31
Speaker
Perfect.
01:10:32
Speaker
And the last question is, what would you want every intensivist and every listener to know?
01:10:37
Speaker
Could be a quote, a fact, or just a thought.
01:10:40
Speaker
I'll share something that I learned very early on in my med school.
01:10:43
Speaker
And I trained at CGS Medical College in Mumbai, India.
01:10:48
Speaker
And our very first exposure in medical school was to anatomy.
01:10:53
Speaker
And there was a skeleton holding another skull that was painted up as a fresco.
01:11:01
Speaker
on one of the walls and right underneath it, you know, they said this for anatomy, but I'm just going to paraphrase it, in life, it's better to have learned and lost than never to have learned at all.
01:11:12
Speaker
Another thing that was also on our anatomy floor was, you are not here to worship what is known, but to challenge it.
01:11:19
Speaker
I feel both of these things have really informed my approach to life as a whole and medicine in particular.
01:11:27
Speaker
And mentorship matters.
01:11:30
Speaker
mentorship and paying it forward really matters.
01:11:34
Speaker
And I think that that's a perfect place to stop.
01:11:37
Speaker
And I appreciate and very grateful for you being so generous with your time and your expertise and paying it forward to our listeners.
01:11:46
Speaker
I hope to have you back, Neha, for discussion of other fascinating topics in the world of neurocritical care.
01:11:51
Speaker
And like we were mentioning before we were recording, I look forward to seeing you in person very soon.
01:11:56
Speaker
Absolutely, Sergio.
01:11:57
Speaker
What a delightful podcast.
01:11:59
Speaker
Thank you so much for the opportunity.
01:12:01
Speaker
And one of the big reasons why we do this is to pay it forward.
01:12:05
Speaker
So thank you for the opportunity to pay it forward.
01:12:08
Speaker
Thank you.
01:12:11
Speaker
Thank you for listening to Critical Matters, a sound podcast.
01:12:14
Speaker
Make sure to subscribe to Critical Matters on Apple or Google Podcasts and share with your network.
01:12:20
Speaker
Sound's transforming the way critical care is provided in hospitals across the country.
01:12:25
Speaker
To learn more, visit www.soundphysicians.com.