Transcript
Speaker: Welcome to Critical Matters, a SOUND podcast covering a broad range of topics related to the practice of intensive care medicine.
Speaker: SOUND provides comprehensive critical care programs to hospitals across the country.
Speaker: To learn more about our programs and career opportunities, visit www.soundphysicians.com.
Speaker: In today's episode of the podcast, we will discuss the management of acute ischemic stroke.
Speaker: Acute ischemic stroke is a major global cause of mortality and severe disability.
Speaker: State-of-the-art acute ischemic stroke care requires a multidisciplinary approach that often includes intensivist and or neurointensivist.
Speaker: Our guest is Dr. Fred Rincon.
Speaker: Dr. Rincon is a neurologist and critical care specialist with expertise in the resuscitation and management of acute brain injured patients.
Speaker: He is professor of neurology at Cooper Medical School of Rowan University and director of the NeuroICU at Cooper University Healthcare in Camden, New Jersey.
Speaker: Dr. Rincon is trained both in medicine and neurology with dual fellowships in critical care, vascular neurology, and neurocritical care.
Speaker: Since this was not enough for Dr. Rincon, he also completed degrees in neuroepidemiology and bioethics.
Speaker: Dr. Rincon is a phenomenal clinician, educator, and investigator.
Speaker: It's an honor to have him back on critical matters.
Speaker: Fred, welcome back to the podcast.
Speaker: Thank you, Sadio.
Speaker: Thank you for having me.
Speaker: Always a pleasure to talk about acute brain injury with you.
Speaker: And today we have, I think, an update on a very important topic.
Speaker: But maybe we could start with just answering why should intensivists care about acute ischemic stroke?
Speaker: That's a great question, Serge, and I can give you a couple of reasons.
Speaker: The main one, right, is because in particular care medicine, you will see 20% of neurological injury in your intensive care unit, and most of that neurological injury is going to be vascular.
Speaker: So, you know, knowing a little bit of ischemic stroke, which is 60 to 70% of strokes, is extremely important for intensives.
Speaker: The second reason, in my opinion, is there's a shortage of neurologists.
Speaker: So, you know, these patients are coming in, right?
Speaker: You know, patients are getting older, they're getting a lot of risk factors, right?
Speaker: And, you know, that's not changing, at least in our jurisdiction, right?
Speaker: You know, prevention strategies, you know, are there, but, you know, patients are still having a lot of risk factors.
Speaker: So they're going to have a lot of ischemic stroke and there are not a lot of neurologists take care of them.
Speaker: much less a stroke urologist.
Speaker: So there's a combination of things going on in the medical field that makes me think that critical care physicians should know about this, how to handle it, and how to take care of these patients.
Speaker: Excellent.
Speaker: And I think that before we dive into more of the management of acute ischemic stroke, there's two important scales that I think would be worth refreshing our audience memories, and there'll be links in the show notes.
Speaker: In terms of managing acute ischemic stroke patients, one refers to diagnosis and assessment of severity, but has direct implications and
Speaker: treatment but also how we monitor them which is the NIH and stroke scale and the other one is more important understanding how these treatments that we implement in the literature have impacted outcomes and that's the modified ranking score could you just give us a little bit of maybe like a 101 on NIH stroke scale and on the modified ranking score
Speaker: Yes.
Speaker: So those are two different scales that tell you different things.
Speaker: So the first one, the NIHR scale is a scale designed to track neurological injury after ischemic stroke.
Speaker: And we have used it not just for ischemic stroke, we also use it for hemorrhagic stroke and
Speaker: you know sometimes people use it for sobriety hemorrhages but in reality it was sort of like coin and designed uh to identify the degree of or the severity of injury after an ischemic stroke and it has uh several realms uh you know 12 uh different realms that assess different uh components of the neurological exam and a trained person can uh deploy a neurological assessment with the anastroscalon under uh three minutes and there are um
Speaker: centers or, or websites that would help you getting trained and certified.
Speaker: You know, it's just going to be extremely easy to get.
Speaker: It's a certification that perhaps you should think about having.
Speaker: I don't think there is any, you know, price tag to it, but, uh,
Speaker: but you could get certified.
Speaker: And it's extremely important because it sort of like tells you how bad or good the patient is.
Speaker: So you can actually categorize people into mild, moderate, or severe strokes on the basis of NIH stroke scale, up to five considered to be mild, six to 12, perhaps moderate, and more than 13 is usually a bad stroke.
Speaker: And it also helps you tracking the patient's improvement or deterioration, right?
Speaker: So in terms of communication, it's an extremely important tool to, you know, predict disability.
Speaker: It also predicts mortality and helps you to, like, track the patient in the hospital, you know,
Speaker: for their admission.
Speaker: As I said, in terms of communication, extremely important, right?
Speaker: Because you are tracking the degree of improvement or deterioration after an intervention.
Speaker: And in general, we consider, you know, worsening of somebody's condition
Speaker: when the NIH stroke scale changes significantly, and we use usually a point, I'm sorry, a four point change in the NIH stroke scale to consider a significant change in the neurological exam.
Speaker: It's part of the benchmarks that our stroke centers use to get accreditation and to track quality improvement programs.
Speaker: So in the first hours of ischemic stroke, you need to document
Speaker: an NIH stroke scale before the administration of thrombolytics or before endovascular thrombectomy and then 6 to 12 hours after
Speaker: the initiation of therapy.
Speaker: And then in the neuro ICU, you can develop even more sophisticated ways of tracking this.
Speaker: I mean, you could ask the nurses to do it, Q1 hour for the first couple of hours, post-DPA, and then eventually, you know, every, you know, six to eight hours for the first 72 hours.
Speaker: And it gives very objective information, you know, you know, to track the patient's condition.
Speaker: So that is severity, right?
Speaker: So it's a scale designed to measure severity of stroke, I'm sorry, and then it can use to predict outcomes as well.
Speaker: The modified ranking on the other side is a measurement of function and it's extremely valuable when you're dealing with stroke patients in general.
Speaker: It was also developed to deal with stroke patients and for this particular one then yes, ischemic stroke, hemorrhagic stroke scan,
Speaker: you know, apply.
Speaker: And it tells function.
Speaker: And when you communicate with, you know, with individuals, with family members, right, you can actually use this because there are,
Speaker: not just based on experience but based on clinical trials and statistics you can actually guide expectations of outcomes right and then you can use this to sort of like explain uh to individuals you know uh you know what the function is or is uh supposed to be you know uh after the intervention so um zero to six is very simple to remember zero no deficits six is death uh one is somebody that has had you know a stroke and has um
Speaker: no symptoms except when perhaps gets tired, you know, and anxious, right?
Speaker: You get symptoms from, from the prior stroke.
Speaker: So there's usually, you know, very mild disability too.
Speaker: It's mild disability is usually a patient that you see, you know, sort of like walking, uh,
Speaker: you know, on the street, perhaps with a limp, but with really no devices, right?
Speaker: Or perhaps with a cane here and there.
Speaker: Three is moderate disability.
Speaker: Somebody has had an ischemic stroke and has a lot of issues with the activities of daily living, perhaps needs some assistance in some of those activities of daily living, walks with a cane or with a device, right?
Speaker: But is able to beat himself or herself.
Speaker: and that sort of thing.
Speaker: A four is severe disability, and it usually represents that patient that is actually handicapped from a stroke and requires a lot of assistance.
Speaker: Sometimes, you know, patients end up with a trach and a peg, but are not vegetative, all right, or minimally conscious.
Speaker: So that's sort of like a
Speaker: an important definition of MRSO4.
Speaker: And then finally, five, somebody with an ischemic stroke that unfortunately is minimally conscious, perhaps evolving into a vegetative state, usually a severe brain injury, a severe stroke.
Speaker: And then six, as I said, death.
Speaker: So the clinical trials have been, in a stroke, have been designed to capture these outcomes in the long term, three, six months, and 12 months down the road.
Speaker: And there, you know,
Speaker: a variety of clinical trials, you know, for different interventions that have used this.
Speaker: And knowing those, you know, when you're having interactions about prognostication, right,
Speaker: this scale becomes very useful.
Speaker: And again, there's also centers and websites that can train you and certify you so that when you give an NIH stroke scale and a modifying ranking scoring in the medical record, that is a certifiable scale, right?
Speaker: So it's also important, right, because if you have somebody with a premorbid condition, right, of let's say five, somebody comes in vegetative and now you're suspecting the patient has a stroke, you know,
Speaker: Yes, you could treat that patient, right?
Speaker: But the jump on improvement is not going to be meaningful, right?
Speaker: Because there's nothing for that patient, right, to improve.
Speaker: The patient is not going to go back to a three or a two, right?
Speaker: So having those discussions with family is also important, right, at the point of care.
Speaker: Are you going to treat somebody with something that has a chance of or some risks, you know, bleeding and...
Speaker: you know, you name it.
Speaker: So that's when the scale becomes really important.
Speaker: And would it be fair to say that three and below is considered a good outcome and four, five, and six obviously are non-desirable outcomes in general?
Speaker: Correct.
Speaker: And that dichotomization, right, historically is what, you know, trials and stroke have sort of like used in the follow-up, right, of these patients, right?
Speaker: But I think ordinal scales are much better now than the dichotomized outcome that you mentioned, right?
Speaker: I think, you know, if you come in with a zero and having to jump to a two, well, perhaps, you know, and then you don't get back to zero, right?
Speaker: You know, even though it's within that sort of like, you know,
Speaker: you know, good outcomes or all that thing, right?
Speaker: You know, you have jumped, you know, excessively, right, within the function.
Speaker: So the ordinal scales in terms of measuring outcomes on the road, I think are more efficient, but you're right.
Speaker: Historically, what you said is what's considered a good outcome.
Speaker: Excellent.
Speaker: And I think that for today's discussion, Fred, before we started recording, we talked about some of the things that I wanted to focus on.
Speaker: We're probably not going to go, obviously, into every single little detail regarding acute ischemic stroke.
Speaker: There'll be references attached to the show notes.
Speaker: But...
Speaker: What I do want to talk about as a starting point for the management is neuroimaging.
Speaker: And obviously, that's the cornerstone of making therapeutic decisions.
Speaker: Historically, CT non-contrast of the brain was what we got, and we got that quickly.
Speaker: Can we start there and then maybe expand on what's next?
Speaker: Yeah.
Speaker: Yeah, so go standard right for it.
Speaker: Dealing with somebody with a stroke syndrome is imaging, right?
Speaker: And you could get a CAT scan within five minutes in the emergency department or in any other institution on the floor, in the circuit unit.
Speaker: I know they have portable versions of this stuff, right?
Speaker: And the resolution is pretty similar.
Speaker: So you have, you know, let's say, you know, a patient, you know, in the CT ICU that just had cardiac surgery and now is semi-parietic, right?
Speaker: And then you need a quick assessment.
Speaker: But let's say the patient has a couple of chest tubes and pacemaker wires, right?
Speaker: a portable scan makes a lot of sense.
Speaker: Now you cannot do perfusion or angiogram with those devices, but I think in the future, because now they're doing this angiograms, right, on these portable scanners and ambulances in Texas.
Speaker: So I don't know who you know about that, right?
Speaker: But this technology is going to continue to revolt and perhaps in the ICU, we might be able to give
Speaker: contrast with a cat scan if you have a good protocol but in general right the non-contrast is the one um that is readily available and it helps you um discern between um or differentiate between hemorrhagic strokes and ischemic stress because that's a contraindication for uh
Speaker: thrombolytics right if you have somebody with an iph or an aneurysm that ruptured uh you know clearly a contraindication to give uh thrombolytics and that's how we start practicing you know and then over the last 10 uh to 15 years right the cp angiogram became an important component right uh of the assessment um because of
Speaker: the evaluation of the anatomy, right?
Speaker: So specifically for these patients been moderate to large or severe strokes, you want to know, right, if you're dealing with a vessel occlusion that requires a mechanical intervention.
Speaker: And the reason for that is very simple is that we learn from the clinical studies, right, in thrombolysis, right, that T occlusions or M1 occlusions, particularly T occlusions, right, meaning the distal, you know, internal carotid occlusion,
Speaker: they don't recanalize that well with just intravenous thrombolytics, right?
Speaker: And that is what opened up all these new era of revascularization, right?
Speaker: It's the T-occlusion proximal of the MCA rarely recanalized just with TPN.
Speaker: If you look at the literature, we're talking about rates
Speaker: around 20% of recanalization, which is the same as placebo in the original NINDS-TPA study.
Speaker: So we're basically talking that if you are recognizing a large-fresin occlusion, a carotid occlusion, or a T occlusion, an approximate MC occlusion, perhaps the chances of recanalizing that with thrombolytics are as good as placebo in the original 1996 NINDS-TPA study.
Speaker: So that's why CTA is so important.
Speaker: And it gives you a lot of information, right?
Speaker: You want data, you want information where you're dealing with these patients.
Speaker: Does the patient have an intracranial stenosis as well?
Speaker: Does the patient have a contralateral carotid stenosis or MCA stenosis that may require a little bit of more liberal blood pressure management down the road?
Speaker: Or does the patient have a dissectional, does the patient have a free thrombus also?
Speaker: Those sort of things, you know, you learn a lot from looking at the CTA.
Speaker: And on the basis of that, then you can sort of like predict, you know, your recanalization, you know, with thrombolytics and then the patient requires an intervention because of what I said, you know, recanalization is really low.
Speaker: Perfusion, right, is a more advanced technique, and not every center has.
Speaker: There's some centers in having corporate perfusion, right, in terms of decision-making.
Speaker: Most of the clinical trials in thrombectomy did not require a perfusion.
Speaker: It was basically an assessment of the degree of ischemia or infarct on a CAT scan, so on the non-contrast CAT scan.
Speaker: And you can interpret that just by looking at a CAT scan, and there is a specific scoring system
Speaker: for it called the aspect score that was designed also to, you know, sort of like, you know, predict, you know, the degree of court, right, versus penumbra, and then the rate of complications, right?
Speaker: So the lower the aspect score, a score of 10 is usually normal.
Speaker: The lower the aspect score, then the higher chance of complications after re-canalization by obvious reasons, because you're basically re-canalizing somebody with a lot of infarct burden, right?
Speaker: So that is from the non-contrast.
Speaker: The perfusion acts a little bit more on the basis of some interpretation of blood flow, right?
Speaker: So it tells you, you know, on the basis of how much contrast is circulating in the arterial and venous phases of the perfusion scan.
Speaker: And the software sort of like gives you a number, and there are more sophisticated, you know, packages right now out there.
Speaker: that can interpret that for you and can give you values of perfusion.
Speaker: And then on the basis of that, people can actually intervene.
Speaker: Some centers use perfusion to predict complications.
Speaker: So a bad perfusion scan will make somebody with a large vessel occlusion not be a candidate for intervention.
Speaker: Some other centers use more the clinical exam and the aspect score without perfusion, right?
Speaker: I think perfusion becomes really valuable
Speaker: when your clock is sort of like unknown, when you don't really know the last thing normal, and somebody wakes up with a stroke, for example, I think perfusion becomes really important to go back to that point that you mentioned at the beginning, the biological clock.
Speaker: And I think imaging is what is going to align you more to the biological clock, meaning the real time of the stroke rather than the clinical time.
Speaker: Because, I mean, sometimes...
Speaker: And you've probably seen this, right?
Speaker: Family members don't know when the lasting normal is, and it's just really devastating not knowing that because you cannot do anything.
Speaker: Or providers in the hospital, you know, a patient goes to the room six hours, nobody checks the patient, and then nobody really knows when the lasting normal is.
Speaker: But imaging can actually help you with aligning you with that biological flaw.
Speaker: Some of the people have used MRI technology and that's actually probably a next generation, right?
Speaker: But getting a stat MRI in the setting of an acute skinic stroke is something that is not pragmatic yet, at least in most centers in the United States, perhaps research.
Speaker: centers are more capable of using a MR technology with diffusion and flare, for example, to determine that biological clock in the patient is amino for thermolysis, for example.
Speaker: There was a study in 2017-18 that basically showed that MRI can assist in giving TPM patients that are waking up with strokes.
Speaker: Excellent.
Speaker: And I think, Fred, that it'd be fair to say, right, that time is of the essence.
Speaker: So getting a plain CT as soon as possible is the first point.
Speaker: And we shouldn't really delay doing that or the potential initiation of, as we'll see, thrombolysis.
Speaker: If we're trying to get like an MRI or CTA, CTP, we don't have that in place.
Speaker: But the initial plain CT will tell you if there's blood, which would be a contraindication for thrombolysis.
Speaker: But it also can give you information of the nature of the stroke as well, right?
Speaker: Like you could see a dense MCA, or you could see, I mean, significant findings that might give you an indication of how severe this is.
Speaker: Now, the CTA and the CT perfusion are obviously a step further that allow you to refine your best therapeutic approach in a much more calibrated way.
Speaker: Is that the way you would think about this?
Speaker: I do.
Speaker: I do.
Speaker: The perfusion can actually help you calibrating, as you're saying, and the CTA gives you enormous information about the anatomy.
Speaker: And if you look at the guidelines, right,
Speaker: IPCTA is becoming more like a standard here right now.
Speaker: So, you know, your stroke protocol, you should have at least, you know, a CTA.
Speaker: And of course, there are contraindications for it, right?
Speaker: But you just have to think about can the patient get contraindications or not.
Speaker: Excellent.
Speaker: So one of the key goals, obviously, in advanced stroke management is revascularization and limiting secondary brain injury.
Speaker: Historically, this really started with the initial studies that suggested that IV tPA made a difference.
Speaker: Those seem to take a long time to really catch on.
Speaker: And it feels, from my perspective as a non-neurologist, that for many years, we probably have underperformed as a medical community in providing TPA to patients who could benefit from it for many reasons.
Speaker: Maybe you can expand on those.
Speaker: But also now there's a new era with a whole set of endovascular therapies that are available.
Speaker: But also, like you said, with a much more biological approach at a time and to windows that seem to continue to expand.
Speaker: So why don't we start with IV thrombolysis?
Speaker: You want to take us through the history and kind of where it stands today?
Speaker: And then after that, we can talk a little bit more about endovascular therapy.
Speaker: Yeah, so the history of thrombolegic is actually a very, you know, sort of like complicated,
Speaker: um, history in, uh, in neurology, uh, cause it started with negative studies, right?
Speaker: It actually started with, uh, you know, uh, you know, people extrapolating, you know, doses for MI to ischemic strokes and sort of like learning very quickly that, uh, that that was not the, the, the, the right way.
Speaker: And then sort of like adjusting the dose, right.
Speaker: And, um, getting to a dose that was more amenable with, uh, uh, with ischemic stroke.
Speaker: But, um,
Speaker: Since 1995, 1996, with NINDS, there's been a lot of criticisms to the way of how we incorporated TPA into our momentarium to treat stroke patients.
Speaker: And when I was in medical school in 1990, right, there was nothing to do for these patients.
Speaker: I mean, you know, these patients would come in, and they would just like, there's nothing to do, and they would just go to the floor.
Speaker: They wouldn't even go to the intensive care unit.
Speaker: They'd go to the floor, and then they would just decompensate and die.
Speaker: I mean, you wouldn't even incubate this patient, right?
Speaker: It was just like massive stroke, nothing to be done.
Speaker: It was like a bad sentence.
Speaker: And then in 1995, you know, the results of the study came out, right, showing a benefit, right?
Speaker: And...
Speaker: A lot of people have criticized that study because the benefit was not really for the primary endpoint.
Speaker: It was for the secondary endpoint.
Speaker: On the basis of that, we started incorporating this stuff for managing our ischemic stroke patients.
Speaker: And then eventually, more clinical trials are looking at this.
Speaker: It started adjusting, dosing and timing, right?
Speaker: when you looked at the pool sort of like analysis of those types over 15 years right you see a clear um effect right and and and the skeptics are always saying well why aren't we considering the negative trials and it could just be a harmful uh intervention for
Speaker: for stroke reasons.
Speaker: And the answer to that is that I haven't seen a negative trial since we started using TPA in the last 50 to 20 years, right?
Speaker: And on the other hand, right, we have become more sort of like careful about selecting patients.
Speaker: And I think patient selection was an issue on the original studies, right?
Speaker: I think for dosing.
Speaker: But right now that we're selecting these patients so carefully, right, so like patient-based selection process,
Speaker: I think the rate of complications is actually lower.
Speaker: And the other issue was, right, the bystander recognition of this stuff, right?
Speaker: So now patients are coming quicker, you know, to the healthcare system, and then you're seeing a lower rate of complications, right, when these patients get thrombolysis or thrombectomy, right, earlier, right?
Speaker: Of course, you're giving this stuff, you know, at the end of 4.5 hours, right, you're probably going to have more complications.
Speaker: um that if you do it in the first 30 minutes of an ischemic stroke so um so that is the the issue right um over the last 15 to 20 years and so like the debate you know surrounding uh internal strombolysis but when you look at the meta announcement there are a couple that i can quote you know in gamma um by jeffrey saber for example uh the incidence of hemorrhagic complications the incidence of
Speaker: of mortality in the hospital, right?
Speaker: The incidence of being discharged to home and having a better functional outcome, right?
Speaker: All time dependent, you know, with intravenous thrombolytic.
Speaker: So when you add up all that information, you're like, well, I don't see any negative effect here, right?
Speaker: So I think it's time to sort of start thinking seriously about, you know, thrombolysis.
Speaker: The problem with thrombolysis, right, that you have a very narrow window, usually three hours with, you know,
Speaker: a lot of contraindications and issues.
Speaker: And then for a specific patient core, you can actually extend that to 4.5 hours with additional contraindications.
Speaker: So in reality, right, 3.5 hours, right, is very short, very narrow.
Speaker: So that's why a lot of patients are not getting it.
Speaker: And if you look at the...
Speaker: The administration rate in the United States, I think we are still like around, you know, 2 to 5%, you know, and when I started, it was like 2%.
Speaker: I guess it's coming up a little bit more because of all the campaigns and American Heart Association, American Heart Association education for bystanders to recognize it.
Speaker: So that's another problem, right?
Speaker: Is that people don't recognize this with enough time to get the patient into the healthcare system.
Speaker: um you know remember what i said about the ambulances circulating you know in texas that approach for example has increased the delivery of of of dpa in in um in in the in the field with really no uh you know major incidents of of complications right the question is can that be implemented everywhere and the answer is well that's typical because it's very expensive right and um
Speaker: And I don't think every jurisdiction has the budget to deal with this stuff.
Speaker: But if you leave more than 30 minutes away from a stroke center, right?
Speaker: Observational studies have shown that you are more likely to not get any intervention just because of that, right?
Speaker: So, you know, how are we going to cover that gap?
Speaker: It's a thing that we can need for the future in Europe, on the other hand, right?
Speaker: You know, you know,
Speaker: you can get access to a stroke center very quickly, right?
Speaker: So these ambulances, you know, they'll make a lot of sense, right?
Speaker: If you live in an urban area where you can get into the hospital within five, 15 minutes of being recognized, but it would make more sense for rural areas that don't have access to stroke centers.
Speaker: And a couple of questions here regarding thrombolysis, IV thrombolysis.
Speaker: So clearly, like you stated, Fred, the literature is solid in improving outcomes, both in terms of neurological outcomes, but also overall mortality long-term, right?
Speaker: And that includes accounting for potential complications like intracerebral hemorrhages, which, as you mentioned, is
Speaker: with the right patient population selection seems to be much lower than people believe it is.
Speaker: But the timeframe you said is three hours from onset of symptoms.
Speaker: So that's onset of symptoms to needle.
Speaker: And it can be expanded to 4.5 hours in some patient populations.
Speaker: But would it be fair to say that the goal is still to try to evaluate or put as many patients as possible at the door of receiving it, right?
Speaker: And then obviously you can go through the contraindications and if they don't qualify, that's okay.
Speaker: But also even for patients who might benefit down a little bit later from endovascular therapy, we should still strive to give IV tPA when possible.
Speaker: Is that correct?
Speaker: Yeah, that's correct.
Speaker: So,
Speaker: Thinking that somebody is a candidate for a thrombectomy and endovascular intervention does not preclude the patient from receiving intaminous thrombolysis as long as the patient is within the 0 to 4.5%
Speaker: window and meets all the inclusion and exclusion criteria.
Speaker: Yeah, that's right.
Speaker: They have tried to, you know, these clinical studies where, you know, you use half of the dose or different weird doses, right?
Speaker: And the answer is just like, no, you know, you use the full dose of TPA and then you get the patient to a thrombectomy.
Speaker: And the combination, right, it's actually, you know, associated with better recanalization scores, right?
Speaker: So, you know, and that's another thing that we should talk about, right, is the difference between tenecteplase and alteplase, right, is that, you know, when you compare both, they sort of like are the same in terms of re-canalization, but when you use thrombectomy or mechanical intervention, right, with tenecteplase, right, that combination seems to be
Speaker: better than without the place.
Speaker: So that's why some centers right now, like my center, converted to administering Thenecteplase for eligible patients when the suspicion for thrombectomy was high.
Speaker: So you're using Thenecteplase now more than before.
Speaker: So the use of tenaplase is increasing because of its improved outcomes when you combined IV thrombolysis with endovascular intervention.
Speaker: Is that correct?
Speaker: Correct, yes.
Speaker: So I don't know.
Speaker: I haven't looked at literature and see if there's more adoption in the U.S., right, for connected place, because, I mean, we fought to give TPA for 15, 20 years, right, so a lot of centers got very used to using out-of-place, right?
Speaker: And as I said, you know, when you compare head-to-head, they are the same in terms of, you know, outcomes and re-canalization.
Speaker: Right.
Speaker: But the problem with Alteplase is that it requires preparation.
Speaker: So it requires a pharmacist to make the solution based on patient weight.
Speaker: Connected piece on the other hand is ready to use.
Speaker: You don't need a pharmacist.
Speaker: So in my experience, some institutions have had a lot of issues with delivering Alteplase on time in the emergency department.
Speaker: And that added to that clock that you start when a patient hits the emergency department.
Speaker: or when the stroke alert is activated, right?
Speaker: Is that, you know, if you're preparing this for five to 10 minutes, well, those five to 10 minutes are costing the patient, you know, 10, 20 million neurons, you know?
Speaker: So it's like 2 million neurons per minute, right?
Speaker: So, you know, that's why, but I haven't, you know, looked in the literature and seen, right, if the United States is adopting more than ectopies.
Speaker: What I can tell you, right, because of the price,
Speaker: is that my colleagues in Mexico, for example, or my colleagues in Colombia or Chile, they're using more tenecaplase because it's easier to use.
Speaker: So it makes total sense, right?
Speaker: I'm not, I don't have any concerns of interest about this trombolitis, but what I'm saying is that it's something that's easier to use and is associated with better outcomes, so why not using it, right?
Speaker: Makes sense.
Speaker: So let's talk a little bit, Fred, of endovascular revascularization or endovascular therapy.
Speaker: And that is a...
Speaker: a more recent history, but also similar, right?
Speaker: I mean, the first studies, perhaps because of how they were designed and the patient selection were not so encouraging.
Speaker: And some people kind of felt very cold about these therapies.
Speaker: But then I think a series of studies showed that they actually have a great impact on outcomes, but also have extended the window of things that are possible for the right selection of patients.
Speaker: So could you talk also a little bit about endovascular therapy?
Speaker: Yes, so I train in different phases of the development of endovascular therapy.
Speaker: So around when I was training at the end of 2000, 2005, 2008, right,
Speaker: This philosophy was getting implemented, and it made biological sense because of what I said, a clot in the terminus of the carotid is not going to dissolve very well with thrombolitis, so why not going after the clot?
Speaker: But that learning curve translated into experiencing some negative trials and some actually harmful trials.
Speaker: And then the other thing that was part of it, besides the learning curve of all of these providers, was the technology.
Speaker: So we were using a device.
Speaker: Well, I wasn't, but these interventionists were using these devices.
Speaker: that were for cardiac purposes or were for some other purposes, right?
Speaker: So there wasn't really like a device that was sort of like adapted.
Speaker: And that technology evolved, right, since 2005, 2015, right?
Speaker: So the first clinical studies, right, on thrombectomy were not promising, in my opinion, because of that learning curve, right?
Speaker: You know, you provided you to do a lot of these interventions to get really proficient with it.
Speaker: And then the technology was actually crappy, in my opinion.
Speaker: But then when these catheters started to evolve, and the companies started to manufacture catheters that were actually designed to treat brain vascular injuries, right?
Speaker: We have the stent retrievers right now.
Speaker: So, those are the ones that actually made everything possible.
Speaker: So that technology and the combination of people getting more proficient with this stuff is what led to the second iteration of clinical studies that actually transform the way that we think about thrombectomy.
Speaker: It's a very robust signal, right?
Speaker: And you see it at the bedside.
Speaker: So, you know, it is incredible seeing, you know, this 80-year-old that comes in, right, with a NIHR scale of 25, totally devastated, right, and then the next morning as an NIHR scale of 1 or 2, it's just like mind-blowing, you know.
Speaker: And no complications, right.
Speaker: It's good patient selection, good, you know, hands, provider hands.
Speaker: and very good technology, right?
Speaker: And I would just throw there very good critical care, right?
Speaker: Because those are the things that you need to sort of like have.
Speaker: When I talk about stroke care, I talk about a multidisciplinary approach.
Speaker: So it's just not the TPA or the provider with a thrombectomy or the ICU, Illinois.
Speaker: It's everything that happens, you know, from the paramedics that recognize the patient, right, to the rehabilitation centers.
Speaker: All of that,
Speaker: sort of like combination, right, of things that happen that makes the outcome even better.
Speaker: So I think those were the issues with thrombectomies that we were learning, A, B, the technology wasn't good, and then the second iteration of clinical studies actually showed a more robust signal, right, and because of the technology and people actually got more experience with it.
Speaker: And I think it's important to emphasize that for these endovascular therapies, we're looking at large vessel occlusions, right?
Speaker: So it's not for every stroke.
Speaker: It's also not for mild strokes.
Speaker: Like you said, I mean, NIH stroke scale, usually it's going to be 14, 15, 16 or above.
Speaker: But could you...
Speaker: Tell us, like, A, what would be the right patient selection and how we get to that.
Speaker: And give us a little bit of idea of the windows, right?
Speaker: Because this can be done, obviously, beyond the 3 or 4.5 hours.
Speaker: And give us a little more of an idea of that, Fred, please.
Speaker: Yes.
Speaker: So for the first question, what is sort of like a good rule of thumb of which patients qualify for surgery?
Speaker: for endovascular intervention.
Speaker: So obviously, if you're doing a CPA, you know immediately if they have large vessel occlusion.
Speaker: We define large vessel occlusion, carotid, double the carotid, MCA, M1 segment, M2 segment.
Speaker: And those are the ones that were included in the second iteration of clinical studies.
Speaker: But can M3 occlusions, right?
Speaker: And when I'm talking about M3, M2, and M1, it's the MCA, right?
Speaker: But can M3 occlusions or ACA occlusions or PCA occlusions or basilar occlusions derive a benefit from it?
Speaker: And the answer is...
Speaker: Possibly, right?
Speaker: But it hasn't been tested, right?
Speaker: There is a study right now trying to look at, you know, do M3 occlusions get better?
Speaker: We're re-canaling, and M3 occlusions recently had distal occlusion, right?
Speaker: So you would get a smaller stroke than if you're knocking out the whole MCA, right?
Speaker: So a good rule of thumb is that if you're using a CTA, right, anyone with a carotid occlusion after the M3 would be an eligible candidate, right?
Speaker: Most of the data, the most robust data for carotid occlusions
Speaker: um, these two occlusions and then the MCAs and the M2s, right?
Speaker: Um, but I, I would not, uh, not discuss, right, somebody with a PCA occlusion, right, with a, uh, interventionist.
Speaker: Why?
Speaker: Because a PCA occlusion could be devastating for somebody, you know, uh, that uses his eyes all the time.
Speaker: So you and I, for example, right?
Speaker: So, you know, are there risks and benefits, um, you know, in favor of proceeding with this?
Speaker: And the answer is, is, is possibly yes, right?
Speaker: Even though there is not a lot of, uh,
Speaker: clinical trial data on those particular territories.
Speaker: So that's in terms of the anatomy, in terms of the CTA.
Speaker: Clinically, right, if you are seeing a patient and you don't have yet information about the CTA, but you're looking at a CT scan and it looks pristine, normal, but the patient has a dense deficit, usually NIHRs scores of more than five would align with the patient probably having a large vessel occlusion.
Speaker: But that's not...
Speaker: That's not a rule in general, right?
Speaker: Because I've seen patients with mild strokes, NIH stroke scale, less than five, that have a large vessel occlusion.
Speaker: You could miss those, right, for intervention, and you're relying only on clinical exam.
Speaker: And there's a clinical study going on called low NIH stroke scale, large vessel occlusion, trying to determine, right, what is the best approach to, you know, treat those patients, right?
Speaker: So in my book, in my cookbook, right, when I'm dealing with somebody with stroke,
Speaker: CT, CTA, regardless of the initial scale, even TIAs, right?
Speaker: I tell the emergency department or whoever I'm working with, right, this patient is a CT and a CTA right now, and let's use a clear contraindication for it.
Speaker: So I hope that answers the first question.
Speaker: For the vascular artery, right, I think that
Speaker: You know, when you are dealing with a disease state that could be potentially devastating, right, I think that a trombectomy makes perfect sense, right?
Speaker: If you are locked in and you are within a reasonable window, you know, you should think about recanalization of the posterior circulation.
Speaker: I'm talking about the vascular artery.
Speaker: Perterial arteries, you know,
Speaker: because of where they are, you know, the collateralization that posterior circulation has from anterior circulation and from the contralateral artery.
Speaker: Perhaps not amenable for interventions unless you're seeing a dissection and a patient has a lot of symptoms, meaning flow failure, you can consider distenting, but those carry a lot of morbidity and mortality, right?
Speaker: So you have to have a discussion with the patient about that stuff.
Speaker: So that is in terms of the territory and the anatomy range.
Speaker: So timing, right?
Speaker: Timing is another variable that you can consider.
Speaker: So the original, you know, the secondary, the secondary, that is, looked at patients between 16 and 24 hours.
Speaker: So right now we are favoring, you know, in terms of timing for endovascular thrombectomy, after 24 hours in both the interior and posterior circulation, right, specifically, right, you can align that biological clock to imaging, right?
Speaker: So if you have a CT, aspects is good.
Speaker: You know, the patient has been down 16 hours, obviously does not qualify for TPA, but you don't see anything
Speaker: in the cat skin that worries you about a big core right of stroke so many originals are actually going after that if they document a large phase of the pollution right and for the posterior circulation uh the rule of thumb was up to 24 hours but you know i've seen cases where people have actually tried you know up to 36 you know but those are exceptional
Speaker: And in terms of the timeframe, Fred, I know that some people talk about six to 24 hours as windows, depending on the findings on a clinical exam, but also on the CTA and the CTP.
Speaker: Could you talk a little bit about the timeframe?
Speaker: Yes.
Speaker: So, I mean, for endovascular intervention, for thrombolysis.
Speaker: Endovascular.
Speaker: Yeah.
Speaker: Yeah, so for endovascular, right, you know, 0 to 24, I mean, if you have somebody, as I said, you know, within a TPA window, right, and qualifies for thrombolytics, right, and you see a large vessel occlusion, you know, you should go, you know,
Speaker: after the occlusion, you know, you are within that window.
Speaker: So I would say 0 to 24 is sort of like what I would be thinking about, right?
Speaker: But again, if you don't have concise information about the timing, right, and the patient's at 36 hours, right, but you don't see anything in the CAT scan and you see a large vessel occlusion, perhaps that occlusion happened not really 36 hours ago.
Speaker: It happened probably like 10 or 12 hours before.
Speaker: And I'm sorry, you know, 0 to 6 hours before, and then you might be able to
Speaker: So in general, right, 0-24 hours is what I would consider some eligibility for TPA.
Speaker: And what I'm saying about the perfusion, right, is that some centers actually use it to predict complications, right?
Speaker: Some interventions don't use perfusion at all.
Speaker: Some interventions just go after the large phase of the perfusion on the basis of clinical exam aspects.
Speaker: Some other centers use perfusion because, right, it gives, there's some, you know, cohort studies that have shown that a mismatch, right, is associated
Speaker: with less complications than if you have a total match in terms of a number, I'm sorry, a total match in terms of core or ischemic infarct, right, in the patient.
Speaker: So somebody that has a completed stroke has more chances of complications.
Speaker: So some centers are using it just to predict complications and not going after the thrombectomy.
Speaker: And there are centers like,
Speaker: like for example, Jefferson have published a lot of this stuff.
Speaker: And I think, you know, from their perspective, it makes a lot of sense to use perfusion to treat patients.
Speaker: But as I said, some other centers, right, like Cooper, we are not using that much of perfusion unless, you know, there are a couple of, you know, indications, right?
Speaker: Patient wakes up with this stroke, nobody really knows when that happened, right?
Speaker: The perfusion can add a little bit more information for therapeutic interventions.
Speaker: And what you're looking for is a big mismatch, like you said, between the core of the infarct and the penumbra, right?
Speaker: So the larger the mismatch, the more likely that they would have lower complications, but also that you could help them with an endovascular intervention.
Speaker: Exactly.
Speaker: Perfect.
Speaker: And in terms of follow-up, immediate follow-up, obviously, we have like, I mean, thrombolysis, perfusion scores that they use in the lab.
Speaker: But ultimately, like you mentioned earlier, once they come back to the ICU and we're following them, it's following the NIH stroke scale that is going to give us, I mean, kind of the best tool to see how they're evolving, correct?
Speaker: Yep.
Speaker: Perfect.
Speaker: Let's talk a little bit of management now.
Speaker: I want to start with some specific complications related to stroke.
Speaker: And the first one, obviously, is cerebral edema and malignant MCA infarctions.
Speaker: But could you talk a little bit about that in terms of how we recognize it, who's at risk, and then what really should be the approach of treatment?
Speaker: Yes.
Speaker: Yes.
Speaker: So that's a great question, right?
Speaker: So really, edema,
Speaker: hemorrhagic complications, and I'll talk a little bit about seizures, you know, are sort of like the main ones that you are concerned about once a patient, you know, in type of the intensive care unit.
Speaker: So if somebody has had good re-canalization, right, with thrombolytics and TPA, right,
Speaker: there is a lower chance of the patient developing seruleidema because if you recanalize and you recanalize normal tissue, right, or penumbra tissue, then, you know, very unlikely the patient's going to have an infarct and it's going to swell, right?
Speaker: So, you know, recanalization scores, you know, I'm talking about TK2B2-3 are usually associated with lower incidence of hemichroniectomy, right, from seruleidema, right, that sort of thing.
Speaker: there's some expectation of some cerebrally dema right the patient has already some core some uh infarct right and um but but the burden right it's it's what predicts best
Speaker: the explosion of cerulean edema.
Speaker: And there are a couple of things, you know, that you could use, you know, from imaging.
Speaker: For example, if you have a two-thirds of a vascular territory effect that you should expect some cerulean edema with brain compression, right?
Speaker: Because most of the real state in the brain is from the, you know, for the MCA, right?
Speaker: So two-thirds of the MCA is associated with
Speaker: uh you know worse outcome more serious email more chance of complication involving the basal ganglia also you know because actually is the stem of the mca so that's usually a proximal occlusion that also predicts um
Speaker: you know, a lot of complications with serulidema.
Speaker: Hypertension and hypotension also, right?
Speaker: It's a U-wave or a U-perv response, right, to this stuff.
Speaker: So if you don't control the blood pressure adequately, right, post-regionalization, or if you let the patient drive too low because of the auto-regulation, then you're gonna cause more serulidema because of basically lactation, right?
Speaker: So you have to be careful also with the two extremes of blood pressure management.
Speaker: And in terms of management, right, medically, right, what we could do, right, I mean, the thrombectomy, as I said, you know, it's a game changer in terms of really considerate email.
Speaker: You get good scores and the patient drops from 24 in the NHL scale to 3 or 2, right, then you know, right, that patient is not going to have
Speaker: a large misprick infarction where you're going to deal with a lot of EDM and midline shift.
Speaker: But let's say that's not the case, then medically, what can you do?
Speaker: So the recommendations are, right, blood pressure controls, as I mentioned, hyperglycemia is the other thing that you need to be so, like, on top of, right, we usually recommend.
Speaker: patients, the nitro sugar levels, 150 to 180, what we call normal glycemia.
Speaker: We don't recommend more intense regimens of glucose management, you know, down to 100, 120.
Speaker: You know, there's a study already done in this research that showed that it didn't help and actually was associated with more hypoglycemia.
Speaker: So, sort of like similar to the Vanderburgh, you know, data, you know, in sepsis and
Speaker: in the medical ICU population.
Speaker: So, nice sugar seems to be okay.
Speaker: The other thing is, I usually preach about this, you know, when people ask me, you know, what to do in the ICU for these patients, right?
Speaker: So, if the patient didn't get good recanalization, by the way, sometimes patients get thrombosis again, right?
Speaker: So, you end up with those patients, they do two, three passes, and then,
Speaker: you know, it doesn't help, right?
Speaker: So there's nothing you can do about it, right?
Speaker: So before we consider surgery, right, can we do something medical?
Speaker: And the answer is yes.
Speaker: You know, there's stuff that you could do.
Speaker: I talk about hyperglycemia management already.
Speaker: There was a study called Games RP, you know, that used sulfonylureas, right, for the management of cerebral edema because these medications inhibit a special aquaporin, you know, channel that decreases the chances of
Speaker: of swelling because of inhibition of free water going into the neurons, right?
Speaker: So that was associated with lesbibylidema and lesbibylidema, right?
Speaker: It didn't really prevent the incidence of hematocytomy.
Speaker: And that's why there's a second study going on with intravenous glibanklumi,
Speaker: trying to look at the same sort of question, but at my institution, we have incorporated glyburide as part of the anti-edema, anti-serial edema protocol for these patients with really aggressive oversight of glucose at bedside, right?
Speaker: Because, I mean, this thing can cause hypoglycemia as well, right?
Speaker: So we do that.
Speaker: And then hypertonic saline solutions, right, and hypersmolotherapy, they can help.
Speaker: And I usually refer to...
Speaker: Due to studies, you know, of ischemic stroke in the United States that have used hyperosmolar therapy to keep sodiums around 150 to 155, I'm talking about headfirst, for example, that showed that the incidence of hemicronectomy was the same in the medical arm and in the surgical arm.
Speaker: that were treated with hypertonic saline.
Speaker: So that's another thing that you can consider, right?
Speaker: So as part of sort of like expert opinion in my institution, right, we have determined, right, that somebody with a the occlusion or an M1 occlusion that doesn't open up with recanalization is going to adapt with this sort of like prophylactic-prevented therapies, like we're right, hypertonic saline, or sodium so 150 to 155.
Speaker: And then you could add
Speaker: Even though there's not a lot of data right now even though there's a few logical data suggesting that You know fever was was bad and associated with exacerbation of single edema, right?
Speaker: But you know, it's gonna be very hard to talk about fever and prevention of Fever or treatment of fever in this era of temperature modulation I just know what to tell you right, but the study that was looking at that call intrepid recently closed because of
Speaker: So that means that they didn't achieve the primary endpoint or any significant difference in the outcomes of people that were treated for fever aggressively versus medical treatment alone.
Speaker: But, I mean, if you still believe in temperature modulation, you could say, well, perhaps I'm going to treat the patient that gets neurologically worse, meaning gets worse.
Speaker: Perhaps I'm going to do a little bit more normothermia, more aggressive intervention, trying to prevent it.
Speaker: So those are the things that you could think about, and then finally, right, if you cannot deal with it, right, if the patient's getting worse, the patient's going to end up with a hemichronectomy if it's a large hemispheric infarction, usually an MCA infarct of more than two-thirds, right?
Speaker: And then, you know, depending on the age, you know, sometimes it helps with functional outcomes in the long term.
Speaker: Usually older people, you're only saving lives, right?
Speaker: So they're going to look the same way six months down the road, right?
Speaker: So they're only saving lives for people that are older than 60, 65 years of age.
Speaker: Yeah, and I think that's important with the hemocrinectomy.
Speaker: You mentioned that as a last, very invasive resort, but usually in your practice and what most people would recommend is to take a medical approach, try to control it, but if you're not successful, then in the right patient,
Speaker: discuss with the family the potential for hemicrinectomy but my understanding of the literature Fred and please elaborate on this is that actually in patients who are 60 or younger a hemicrinectomy done in a timely fashion will improve mortality and also will probably improve their modified ranking score is that correct
Speaker: Yeah, that is correct.
Speaker: It's actually neuroprotective when you look at the shift in the MRS from the historic clinical studies.
Speaker: And what you're saying is, you know, right on the spot, you know, younger patients at that 60, you should experience that effect.
Speaker: More than 60, perhaps not on the basis of...
Speaker: studies in Europe.
Speaker: But what I have to say about hemicronectomy, and again, I haven't looked at this systematically or scientifically, we looked at this in our own experience at Jefferson, where I used to work before.
Speaker: The incidence of hemicronectomy decreased with a re-canalization score.
Speaker: So we saw less hemicronectomies with patients getting actually re-canalized to
Speaker: very good levels, right?
Speaker: So I think that if you looked at this in some database, right, you will see that recanalization will be associated with decreasing on the use of hemichromatomy.
Speaker: And I hope that that is the trend, because, I mean, you are saving them from this very morbid surgical intervention.
Speaker: It has a lot of complications, right?
Speaker: So, as you mentioned.
Speaker: Well, and absolutely, if you think about cerebral edema as a result of secondary or extensive neurologic injury, and the whole point of revascularizing a patient is to prevent that.
Speaker: So it would make sense, right, that if we're successful, that we should see lower rates of malignant cerebral edema or malignant MCA infarctions, and hence less patients who would need a hemichrome anectomy, which is obviously, like you said, a good thing.
Speaker: The other complication that I wanted to ask you about, and you mentioned that it was hemorrhagic transformation, obviously, especially in patients who received IV tPA, but this can also happen without IV tPA.
Speaker: And just in terms of how to recognize it, how to approach it in terms of therapy.
Speaker: Yes.
Speaker: So hemorrhagic transformation, if you look at the original rates, 60 to 70%,
Speaker: you know, post-DPA and depending on the burden of infarct, right, the higher the core, right, and the lower the mismatch, meaning more infarct.
Speaker: And that's what CT perfusion would be very good at, you know, telling you, right?
Speaker: Those are the things that are associated with hemorrhagic transformation.
Speaker: Hemorrhagic transformation is also associated with hypertension, right, especially after recanalization.
Speaker: That's why the blood pressure guidelines for a post-thrombolytic patient is systolic blood pressure less than 180.
Speaker: And depending on the recanalization score, the patient has gotten thrombectomy.
Speaker: You can also guide blood pressure parameters, right?
Speaker: So if the patient gets a good recanalization, TK2B,
Speaker: three um then you know uh the the post hoc analysis or the the uh retrospective analysis right of of the studies that looked at this uh revascularization business have shown that just a little bit of pressure perhaps 120 to 140 are associated with better outcomes right and and and the answer is you know is that after re-canalization right you have to be very uh anal or very um
Speaker: strict about the top and then the low blood pressure parameter, right?
Speaker: So that's a second thing.
Speaker: So TIKI 2B or less, I'm sorry, not TIKI 2A or less, perhaps more liberal blood pressure, perhaps less than 160, right, would be good.
Speaker: And then if you don't get any recanalization,
Speaker: you know, TQ1, perhaps you should go back to less than 180 if the patient got TPA, or perhaps even considered a higher blood pressure level to allow collaterals to circulate.
Speaker: But, you know, that's a decision that you can make, you know, after knowing the anatomy of the patient, knowing the interventions that were provided and the complications that happened or didn't happen during the procedure.
Speaker: So,
Speaker: Hyperglycemia also associated with hemorrhoid transformation.
Speaker: So, as I said, you know, normal glycemia is like the goal in the ICU.
Speaker: Diabetic patients are at higher risk of developing complications.
Speaker: Of course, if you have somebody that was taking
Speaker: an inequivalent, right, direct oral inequivalent, right, and more like used right now for prevention stroke in AFI patients.
Speaker: So you don't usually reverse those for an ischemic stroke, right, so many people are going after those clots in the setting of DOAC, right, even though haven't seen that much of major, you know,
Speaker: greater complications and interventions are okay with that.
Speaker: That's another consideration.
Speaker: Any quiolopathy in general, right?
Speaker: The use of aspirin and antiplatelets are not associated with hemorrhagic complications except the combination of dual antiplatelets, right?
Speaker: So when you combine aspirin with something else, you are more likely to have more hemorrhagic complications.
Speaker: And there is an antiplatelet that, you know, we try to use in ischemic stroke and we stop using it because of the incidence of hemorrhagic transmission.
Speaker: It's called parazugrel.
Speaker: We don't use it
Speaker: that much that's probably the only one that I would say may be associated with hemorrhoid transformations um talk a little bit about seizures too uh you know the the the thought process for seizures after ischemic stroke is that you don't see that much of seizures you know in the uh in the uh aftermath of ischemic stroke with thrombolysis thrombectomy unless the patient gets a lot of like
Speaker: complications gets a subdural or gets a hemorrhagic hemorrhage from a dissection, right?
Speaker: And perhaps, right?
Speaker: But prophylactically, we don't use antiepileptics, post-ischemic stroke, right?
Speaker: Only when we suspect that the chances of having a seizure are high.
Speaker: You know, as I said, hemorrhagic complications may be one of them, right?
Speaker: Hemichronectomy or craniotomies, right?
Speaker: Maybe a second one.
Speaker: But prophylactically, we don't use antiepileptics.
Speaker: Excellent.
Speaker: And the other thing I wanted to ask you in this portion, which is not something that I have seen commonly, or I've not seen at all, actually, but is well described in the literature, is in patients who get out the pace, they can have an anaphylactic reaction.
Speaker: Any comments on recognizing and managing this?
Speaker: Yes, it's reported in the literature.
Speaker: I think the incidence is about less than 2% if I'm around 0.62%, if I'm not wrong.
Speaker: But yeah, I've seen probably two or three patients post-TPA that develop this allergic reaction that is…
Speaker: similar to angioedema, right?
Speaker: And actually end up being intubated, right?
Speaker: It's rare.
Speaker: It's usually in the same side of the stroke.
Speaker: I don't ask me why.
Speaker: I've asked, you know, several colleagues about this, and I don't know if these...
Speaker: you know, it's related to a deafferentation somehow, ipsilateral to the stroke from adrenergics, you know, from the adrenergic system, right, and somehow these vessels, you know, in the mouth or in the throat are sort of like vasodilated, right, and then you give TPA, and then there may be also an effect of, you know,
Speaker: you know, endothelial stuff.
Speaker: I have not been able to explain it very well, but I've seen two or three cases with that stuff.
Speaker: And then the normal reaction, right, is that you need to deal with that airway, right?
Speaker: Protect the airway at least for 24 hours and then try to get the patient better treatment as angioedema.
Speaker: Perhaps some H2 blockers, you know, may help.
Speaker: I don't think steroids help that much, but
Speaker: So the treatment would be kind of, if you're infusing the alteplase, you would stop it.
Speaker: I mean, steroids, obviously, like you said, who knows if they help, but people usually get them and then treat them similar with H1 and H2 blockers.
Speaker: And if needed, maybe some epinephrine.
Speaker: So no different than you would treat any other adenemias.
Speaker: This is just recognizing it in the setting, right?
Speaker: Yes, and it's treansian.
Speaker: It's usually treansian.
Speaker: Maybe a genetic disposition to some bradykinen pathway.
Speaker: I don't know how to explain it.
Speaker: Perfect.
Speaker: So we talked about some very important aspects of general ICU management in the context of managing cerebral edema, preventing it, and just providing, I think, good care, especially post, hopefully, revascularization.
Speaker: But I wanted to touch on two more or expand a little bit on one thing.
Speaker: and talk a little bit about airway management.
Speaker: Any general considerations, Fred, that you could give us first on airway management in terms of oxygenation and ventilation for these patients?
Speaker: I think the same principles for any critically ill patient.
Speaker: You have a patient that requires airway protection in the setting of outer mental status or a neurological injury.
Speaker: you should get the airway protected, right, in terms of oxygenation.
Speaker: Avoiding both hypoxia and hyperoxia, I would say, are important in terms of hyperoxia.
Speaker: There's been a lot of observational studies on this stuff, right?
Speaker: But I think over the last 10, 20 years in the field of critical care medicine, we have to regress to the mean, right?
Speaker: So we used to do supermedicine for certain disease states.
Speaker: In subrana hemorrhage, we used to hypertense them and give them hyperbulimia and give them a lot of blood transfusion.
Speaker: We learned that that doesn't work.
Speaker: For sepsis, it's the same thing.
Speaker: We used to give them a lot of fluids, and then now it's like, perhaps we shouldn't.
Speaker: It's still the same thing for...
Speaker: for oxygenation and they actually just keep a a pao2 you know 70 to 100 that's totally fine right um and then a saturation of more than 92 that's totally fine if you're following that in terms of co2 ventilation right normal carvia right you know 35 to 45 it's sort of like okay unless you're dealing with a patient with uh you know pulmonary comorbidities that you know requires a higher co2 you know to maintain a normal uh phs because the patient has
Speaker: uh coronary disease right um during the uh four three or four attacks of code i don't remember if it's three or four i just lost count but uh we saw a lot of kobe patients with uh uh you know lung you know acute lung injury right from kobe with ischemic strokes right and then we ended up you know managing both in the in the medical icu so um but the guidelines were the same you know try to keep uh
Speaker: a pO2 of 70 or above, right?
Speaker: You know, people have suggested to do neuromonitoring in those patients that are comatose, right?
Speaker: You know, perhaps, yes, you know, I cannot tell you, you have an ischemic stroke, you know, if you should go down that path here unless you have, you know,
Speaker: uh, established protocol, right, and, and know what to do with the, uh, with the information, right, but, um, uh, but that's in terms of oxygenation and ventilation, you know, um, for the weaning, right, and, and, and this is an important thing, right, is that, um, I mean, sometimes patients, you know, get better, and then they, they get weaned, and then they get liberalized from, from the ventilator, and, and, and that is great.
Speaker: Sometimes patients with ischemic stroke, especially the ones that don't respond to therapies, end up with a hemichroneectomy, right,
Speaker: may need a tracheostomy, right?
Speaker: So when to do, timing of tracheostomy is another consideration when managing the airway.
Speaker: And there was a study, you know, and we were so like enthusiastic about the set point study, you know, trying to see if early tracheostomy was associated with better outcomes in neurological patients.
Speaker: It just didn't include ischemic stroke rate.
Speaker: And I heard that, I heard not, actually I read, you know, I think it was published in JAMA a couple of months ago.
Speaker: There wasn't any major difference in long-term outcomes.
Speaker: But I just want to emphasize a couple of things about early tracheosis.
Speaker: I'm a fan of early trachis in patients with severe neurological injury that are not so hot in the intensive care unit.
Speaker: And I think that if you trach early, you're preventing a lot of things down the road.
Speaker: And sometimes families get...
Speaker: stuck on the issue of, oh, is this going to be permanent or not?
Speaker: And you have to elaborate a little bit on that, right?
Speaker: But I think early tracheostomy is associated with better chances of weaning from the ventilator in these neurological patients.
Speaker: I think ventilator free rates are higher in patients that get early trach, they can mobilize faster, they can go to rehab faster, they get less exposure to anesthetics and sedatives.
Speaker: that you need to use when you're ventilating them in terms of infections like ventilator events, ventilator-associated pneumonias.
Speaker: In my experience, I think that it helps you with decreasing the incidence of those complications in your unit.
Speaker: i'm a fan of early tracheostomy and the set point study use a scoring system to sort of like predict right and i think the scoring system works well at at predicting right who may need a tracheostomy in the long term and you use not just neurological variables you also use medical variables right that uh sometimes uh you don't think about you know when you have a patient with a stroke right you know you know
Speaker: Does a history of pulmonary disease or a history of pulmonary or lung injury, you know, in the acute setting predict an infratracheostomy?
Speaker: And the answer is yes, you know.
Speaker: So, you know, those sort of things, you know.
Speaker: Does the incidence of hemicraniectomy, right, predict, yes, it does, right, because it's a cumorbit stuff, right, so in the research intervention, right.
Speaker: So when you have all these points, right, and you end up with a high set point score, right, you can't argue that perhaps, you know, early trade, but as I said, it's not associated with better functional outcomes that if you do it late.
Speaker: But in my opinion, and this is just my opinion, Sergio, I think it helps you mobilizing patients faster, you know, trying to do stuff faster for these patients.
Speaker: And I think that obviously it's something hard to study, Fred, but also, and this is based on a very small end, but speaking with patients who have survived or recovered prolonged illness, more than one has had tracheostomies and I've talked with them and they kind of said that
Speaker: Why didn't you do it earlier, right?
Speaker: I mean, it kind of is much more comfortable.
Speaker: It's safer.
Speaker: The patients, I mean, can interact better, require less medications.
Speaker: So there's other advantages that maybe are hard to capture just in a mortality analysis, but that's definitely something to consider.
Speaker: The last thing I wanted to talk about, Fred, which you already did touch about, but I do think is an important aspect of what we do as intensivists in these patients is blood pressure management.
Speaker: And as you alluded to earlier, the relationship between blood pressure and outcomes is a J or a U curve, right?
Speaker: So very high blood pressures or very low blood pressures are going to be associated with problems.
Speaker: But what I do think is worth mentioning is the approach we should have based on where our patient falls in therapeutic interventions, right?
Speaker: So
Speaker: And I'll give you three categories.
Speaker: And I just want you to tell me how you would manage the blood pressure.
Speaker: So the first category is a patient who's not a candidate for TPA and is not a candidate for endovascular therapy.
Speaker: Yeah, so if you look at the guideline, they tell you that the SDP should be less than 220, and I sort of like agree with that, right?
Speaker: But you have to look at the patient as a whole, right?
Speaker: So, you know, would 220 be okay for his heart or for his lungs or for his skin, you know, that sort of thing?
Speaker: That's a decision you need to make, right?
Speaker: So let's say the patient has heart failure, has an EF of 20%, right?
Speaker: has had ischemic stroke, and then has a history of coronary artery disease.
Speaker: So the question is, would you allow that patient to have a blood pressure of 220?
Speaker: And the answer is probably, I would probably be a little bit more conservative.
Speaker: Perhaps I would say, perhaps 180, and then I will see the patient at the bedside, right?
Speaker: But again, it's on the basis of patient's variables, right?
Speaker: Because you have somebody with CAD or just had a stent, you know, it has an EF of 20%, has SVP of 220, may not...
Speaker: Her heart may not like that amount of blood pressure.
Speaker: Second group of patients is a patient who comes in with very high blood pressure, but is within the time frame for IV thrombolytics.
Speaker: Yes.
Speaker: So, you know, high is usually more than 220, right?
Speaker: So, by consensus, right, before we give TPA, we have to lower the blood pressure, you know, lower than 220 to make the patient...
Speaker: amenable for TPA.
Speaker: And then after he gets a TPA, the blood pressure has to be lower than 180, right?
Speaker: So when you think about the auto-regulation, right, that patient is actually on the right side of the auto-regulation.
Speaker: So yes, when you're lowering the pressure, you're just basically trying to prevent the capillaries to leak and then sort of like explode.
Speaker: and then prevent hemorrhagic complications.
Speaker: So I would say for this particular patient, perhaps 180.
Speaker: And when you look at the step down from 220 to 180, it's usually not more than 20%.
Speaker: So you are still within that sort of like rule of thumb that in hypertensive urgency or emergencies, right?
Speaker: Perhaps you should lower the MAP or the SPP by no more than 20, 25% of the baseline.
Speaker: Excellent.
Speaker: And the last category of patients are patients who are being wheeled off to the endovascular lab for endovascular revascularization.
Speaker: Yeah, so same thing as the ones above, right?
Speaker: If the patient didn't get TPA, then 220.
Speaker: If the patient got thrombolytics, perhaps less than 180.
Speaker: And then after recanalization, we can decide about where to clamp it, right?
Speaker: If we get successful recanalization, TIKI 2B to 3, perhaps a blood pressure less than 140 and more than 120 for the first 24 hours would be ideal.
Speaker: And if the patient didn't get very good recanalization, perhaps 160 or less would be also ideal.
Speaker: And in terms of drugs, Fred, what drugs do you like to use for these patients?
Speaker: I'm just curious.
Speaker: For blood pressure?
Speaker: Yep.
Speaker: Yeah, so I like the calcium channel blockers, and I also like the beta blockers, right?
Speaker: So we're using the neuro-ICU combination of either nicardipine or clavidipine or intravenous labetalol, right?
Speaker: I think there's a shortage for labetalol, so we've been using more nicardipine and clavidipine.
Speaker: Excellent.
Speaker: Well, I think that obviously we've touched a lot during our discussion.
Speaker: I think a lot of very important topics.
Speaker: The last thing I wanted to touch as we close the topic on acute ischemic stroke is just the road to recovery.
Speaker: And there's been a big push in the ICU in general for liberating patients from critical illness, for early mobilization, even in patients on the
Speaker: on the ventilator.
Speaker: Early mobility is a big part of what we do in the A to F bundles.
Speaker: Could you just talk a little bit about early mobilization and rehab?
Speaker: There seems to be kind of like a perfect dose, not too much, not too early and not waiting too long.
Speaker: But if you could just comment where the literature stands on that right now, Fred.
Speaker: Yes.
Speaker: So there's been a couple of clinical trials looking at early rehabilitation in patients with ischemic stroke, specifically post-
Speaker: thrombolysis, right?
Speaker: And then they found that if you mobilize patients within four hours post-DPA or thrombolytic, they had worse outcomes, right?
Speaker: But when you look at the details of those clinical studies, right, is that the amount of energy or METS, metabolic expenditure, that they were exposing the patients to were to high amount of pain, right?
Speaker: So, you know, these were people that had just had a stroke and then they were asking them to, you know,
Speaker: you know, you know, walk the room and then play, you know, in a soccer field.
Speaker: And I'm like, no, I mean, I think early mobilization with sort of like, you know, individualized approach to the patient, right, with minimal, you know, metabolic exposure, right, may be ideal.
Speaker: So that's the criticism that I have to do this.
Speaker: So some institutions actually adopted a no mobilization,
Speaker: post-tPA on the basis of that particular study.
Speaker: My experience is that, right, if you're using isometrics, if you're using L-immobilization to the bed and assistance, right, perhaps, you know, the
Speaker: the effect is not there.
Speaker: So it really depends on what type of exercises they're using, right?
Speaker: But I am a fan of early mobilization, liberation from mechanical ventilation early, right?
Speaker: And early rehabilitation.
Speaker: I mean, that should be sort of like the goal, right?
Speaker: And the issue that we have both in the ICU and in the hospital setting, you know,
Speaker: it's your inability to discharge these patients to rehab.
Speaker: The rehab that they get in the hospital is not as good as the rehab that they're getting in the rehab center.
Speaker: So sometimes families, they're adamant about not being discharged, right?
Speaker: But in reality, a physical therapist can only do one or two hours of rehab two or three times per week in some patients in stroke centers, right?
Speaker: So that is a challenge to getting people to rehabilitation, right?
Speaker: So, you know, we usually start within 24 hours.
Speaker: As I said, you know, because of my criticism, I don't believe that early rehab is associated with abnormal outcomes in post-EPA patients.
Speaker: And, you know, we're just trying to wean fast, you know, and liberate for mechanical ventilation fast.
Speaker: Excellent.
Speaker: So, Fred, thanks again for giving us, I mean, this comprehensive overview and update, obviously, on acute management of acute ischemic stroke.
Speaker: As you said, it's something that requires a multidisciplinary team and a critical care specialist where they're a medical intensivist, surgical intensivist, or neuro intensivist or anesthesia intensivist are part of that, right?
Speaker: You've been to the podcast before.
Speaker: You've been a guest before, so you know the drill.
Speaker: Would it be okay if we close with some questions unrelated to stroke?
Speaker: Yes, yes.
Speaker: So in the last couple of years, two to three years in the COVID era, have there been any books that have really influenced you or that you gifted to others?
Speaker: Yeah.
Speaker: So I, uh, I always talk about the, uh, uh, the stoic books and I read a couple of other, uh, you know, stoic books, uh, you know, besides some Marcus Aurelius, I think that was the last one that I recommended, but, uh, um, I, I, I recently, uh, went to training administration and, uh, I read a book that really like made a difference in the way that I approach, um, you know, um, colleagues in general and, and, uh,
Speaker: and family members in general, right?
Speaker: And the book is an administration book, right, for leadership.
Speaker: But, you know, I think it talks more about than administration.
Speaker: It talks a lot about, you know, how to conduct yourself in general in life.
Speaker: And it's called The Servant.
Speaker: It's a book about leadership and the type of leadership that I use now.
Speaker: It's called Servant Leadership, right?
Speaker: And it inspired me to change the approach to just not administer stuff, but also how I conduct myself in general with family and friends, et cetera.
Speaker: So very inspiring.
Speaker: We'll definitely put that in the show notes.
Speaker: And I think it speaks to a couple of things, Fred.
Speaker: First is that when you think about the purpose of leadership, right, it's not to serve your own purpose or your own game, but it really is to make a difference in the life of others.
Speaker: And I think that whole approach of servant leadership is very important.
Speaker: It's interesting, and I know that we share an interest in old philosophy, like you mentioned with Marcos Aurelius, but I also had a chance to recently read a book by Plutarch, which is over 2,000 years old, and it's about leadership and kind of the same idea, like why would people go into leadership?
Speaker: It's about making a difference and serving the community or others.
Speaker: And definitely, I have not read The Servant, but I love the idea.
Speaker: I will put it in the show notes, and I,
Speaker: I will definitely check it out.
Speaker: The second question is a variation of a question I've asked you in the past, but what do you believe to be true in neurology or neurocritical care that most other intensivists don't believe?
Speaker: That's a loaded question, Sergio.
Speaker: I think that...
Speaker: You know, as you mentioned before, right, I'm training both, and you train me, by the way.
Speaker: So, you know, I've seen a lot of differences in approach, okay?
Speaker: And over the last 20 years, I think the field of neurocritical care has been trying to, you know, demonstrate, right, that there is a role for neurocritical care specialists in
Speaker: in the United States.
Speaker: So I just have to tell you, right, that there is a difference of how we see things as compared to people that have not trained or get exposed on treating patients with neurological injury, right?
Speaker: And we just talked about some of them, right?
Speaker: Sort of like this very sophisticated, you know, you sort of like calibrated way that you mentioned, right, to approach this stuff.
Speaker: And I'm not saying, right, that, you know, we do better in the neuro ICU than in the medical ICU.
Speaker: I think that the difference in reality is the team, okay?
Speaker: It's not the provider because you could train, you know, in the neuro ICU, but if your nurses don't get it, right,
Speaker: If your residents don't get it right, if your respiratory therapy don't get it right, then you are going to have issues with managing this patient.
Speaker: So I think the difference in neurocurricular care is the team that you're calling neurocurricular care.
Speaker: It's really not the provider.
Speaker: However, when you look at the literature, I would actually...
Speaker: I suggest the listeners of the podcast to look at the latest JAMA article on neurocritical care that basically shows the differences in the outcomes on neurocritical care patients being treated by a team of neurocritical care providers.
Speaker: We'll definitely put that in the show notes as well.
Speaker: And what's super interesting, Fred, is that the concept of the team, right, translates to other areas that has been studied.
Speaker: There's a study that I have often quoted and showed when I talk about team building, the science behind team building, that looks at CT surgeons that operate at more than one hospital.
Speaker: And traditionally, the belief is that the number of cases a CT surgeon has done correlates with their outcomes.
Speaker: But what's very interesting is that that number of cases does not translate from hospital to hospital, which means that at the end of the day, what really matters is not the independent surgeon, but the team that works with him at a given place.
Speaker: And I think it extrapolates exactly to what you were saying, which is great.
Speaker: And I have not seen this JAMA article.
Speaker: I have not read it at least.
Speaker: So I'm going to be very interested in picking that up as well.
Speaker: So I will put it in the show notes.
Speaker: And again, the final question, just to close, Fred, what would you want every intensivist to know?
Speaker: Could be a quote or fact or just a thought.
Speaker: I think that, you know,
Speaker: As a critical care physician, I think the concept of plasticity when you're dealing with neurological injury is something that you need to think about when you're treating these patients.
Speaker: Historically, we've been very nihilistic about
Speaker: uh, you know, treating these patients for, you know, whatever biases we have had, you know, uh, it could be personal biases or, or professional biases, right.
Speaker: But the concept of neuroplasticity and secondary neurological injury, you know, which is what we are, we have discussed here in the podcast, right.
Speaker: How to prevent that stuff, right.
Speaker: You know, it's, you know, an important concept because it will transform the way that you look at, uh, a neurological injury, right.
Speaker: If you treat these patients appropriately, if you deliver interventions that are associated with neuroprotection, and we talked about some of them for ischemic stroke, you will see down the road, if you have the chance,
Speaker: how those patients, you know, recover, right?
Speaker: So as critical care doctors, we don't have that much of experiencing patients in the clinic or stuff like that, right?
Speaker: But if you believe me, these patients will surprise you, right, if you treat them appropriately.
Speaker: So, you know, what I would like everyone to know, right, is that, you know, being nihilistic, perhaps up front, it's not a good idea, right?
Speaker: You still have a couple of days or hours, right, to determine, right, where the patient is going
Speaker: in terms of recovery or not, right?
Speaker: And being pessimistic at front, perhaps, in my opinion, not a good idea, right?
Speaker: Yeah, sometimes you see it clearly, black and white, right?
Speaker: You know, yeah, the patient's not going to do great, right?
Speaker: But sometimes, you know, you just have to give the patient time, right?
Speaker: And they will recover.
Speaker: And that's a great place to stop because I do think that especially with neuro patients, people who are not trained in neurology, like myself, who don't see patients long term might have an overly nihilistic approach to what they see initially.
Speaker: And you're right.
Speaker: I mean, even the initial TPA studies, part of the problem in adoption was that the real effects are 90 days post, right?
Speaker: Not necessarily in the hospitalization.
Speaker: So we failed to appreciate that it might be a big difference for that patient.
Speaker: Fred, always a pleasure to have you on.
Speaker: We'll definitely have you back on soon.
Speaker: And now that knock on wood, COVID seems to be...
Speaker: Less of an issue.
Speaker: I'm sure that we will cross paths in person soon.
Speaker: So look forward to talking with you in person as well.
Speaker: Thank you very much for sharing your expertise and your time with us today.
Speaker: Thank you for having me.
Speaker: Thank you for listening to Critical Matters, a sound podcast.
Speaker: Make sure to subscribe to Critical Matters on Apple or Google Podcasts and share with your network.
Speaker: Sound's transforming the way critical care is provided in hospitals across the country.
Speaker: To learn more, visit www.soundphysicians.com.
