Ep. 173: Acute Intracerebral Haemorrhage: Modern Management Strategies

00:00:00: Welcome to EA Youngcast, your weekly source for education, research and updates from the European Academy of Neurology.

00:00:13: Hello everyone and welcome to the news episode.

00:00:16: My name is Benedetta Storti and I'm a young neurologist at the Instituto Neurologico Carlo Besta in Milano, Italy.

00:00:23: And I have a great pleasure from the rate in today's session.

00:00:26: It is a true honor to introduce our guest.

00:00:31: she is head of the department of neurology in Dill University Hospital and also professor of neurology in the same place.

00:00:38: And Professor Codonier is an internationally recognized speaker, a researcher, a neurologist for our outstanding contributions of the field of stroke, and in particular in Cereborus Movesa disease.

00:00:53: She is among the authors of the most recent European Stroke Organization guidelines on intracerebral amourage.

00:01:00: And she's also served as the first author of the latest international recommendations on the management of cerebral myelotentropathy.

00:01:09: Well, she is for sure for all of us an inspiring researcher and clinicians and for me also an inspiring woman for sure.

00:01:16: And Professor Codonier, thank you very much for joining us today.

00:01:19: So let's begin with the questions.

00:01:21: And to begin, I would like to ask you to outline the fundamental principles that currently guide the acute management of intracellular amortage, according to the just mentioned most recent European stroke organization guidelines.

00:01:39: Thank you, Benedetta, for this kind of introduction.

00:01:42: I'm very happy to share my views about this very important topic in stroke management.

00:01:51: Although it has been neglected for many years, and I really think that We've come so far to improve ischemic stroke management that now it's the turn to look at patients who are suffering from intracerebral hemorrhage.

00:02:10: So the first key message is really to integrate the fact that ICH is an emergency.

00:02:19: This is a vital emergency in the same way as it is for ischemic stroke.

00:02:26: So the concept of time is brain is the first thing to remember when you have to manage a patient with ICH.

00:02:35: And it's probably even more important with ICH, because we now know that in ischemic stroke, there are things that you can reverse.

00:02:45: In intracerebral hemorrhage, what you see on the CT scan at admission, you can't reverse it.

00:02:53: So your first goal is to limit hematoma expansion.

00:02:58: You want the bleeding to stop.

00:03:00: And that's really, I think, the most important thing to keep in mind when you have to deal with an ICH patients when you are in the emergency room.

00:03:11: Yeah, my first message is time is brain in ICH too.

00:03:15: Which is definitely super effective as a first message to be taken.

00:03:20: And I just want to move a little bit specifically to blood pressure management, which has always been a central issue for sure.

00:03:29: What are the current recommendation blood pressure targets and how have trials such as interact and attack shape these recommendations?

00:03:37: What would you say the earlier, the better when lowering the pressure or do we need to be more cautious?

00:03:47: So we have to understand why we do that.

00:03:51: Why do we want to lower blood pressure?

00:03:54: Well, we want to do that because we want to limit the active bleeding.

00:04:00: So we want to limit hematoma expansion.

00:04:04: And from a pathophysiological perspective, hematoma expansion is happening within mainly the first three hours.

00:04:14: So very short time window.

00:04:18: So it means that If we want to manage blood pressure and if we want to lower blood pressure, we have to be as quick as possible.

00:04:27: I really think that we really have to think about door to needle, door to blood pressure targets, the way we think about door to needle time with IV thrombolysis.

00:04:41: So as soon as possible, the best is really the golden hour.

00:04:47: I think it also applies for ICH.

00:04:50: so lower systolic blood pressure as soon as possible below one forty.

00:04:58: and the tricky thing in terms of management is really to be able to to reach this tiny BP window because we don't want it to draw to to be too low.

00:05:12: so we don't want it to be below one thirty because we know that it may have some impact on on on on the kidney function and we know that from attack two.

00:05:24: but we want to be also lower than one forty.

00:05:27: so between one forty and one thirty is really what we would like to achieve as soon as possible ideally within the first hour.

00:05:38: Yes, I really like the comparison with ischemic stroke management, which is something that is definitely more, I would say, fashionable, maybe, and that's why Interestable Emerger is a little bit neglect.

00:05:49: Now the interest is moving to this direction also, also thanks to reversal agents, for example.

00:05:56: And so my next question would like to go in depth about that.

00:06:01: I would like to ask you, what's your opinion about reversal agents like Idaro Chizumab and Excellent Alpha, which are increasingly becoming available.

00:06:10: And do you think that they are feasible in the real world clinical practice?

00:06:16: And I mean, not only in France, in Italy, but I mean, in the real world.

00:06:22: So if we take the, first of all, the Western countries perspective, I would say that for reversal agent, it's about the same as blood pressure.

00:06:34: So it has to be as quickly as possible because the aim of this strategy is to limit hematoma expansion.

00:06:42: So you have to be very quick.

00:06:44: And before talking about what type of treatment or type of pharmacological agent we may want to use, it really raised the point of our organization.

00:06:57: It means that of Of course, it's very important to have a pre-hospital evaluation of those patients and in France, I think in Italy, in a lot of European countries, people are advised to call one, one, two.

00:07:16: for emergency so that they are recognized as potential stroke.

00:07:22: And as a neurologist, when you are inside the hospital, you have to know that this patient is arriving and you have to know that this patient is under anticoagulation treatment.

00:07:34: So from an organizational perspective, it's very important pre-hospital notifications so that everything is ready when the patient arrives.

00:07:42: Of course, you don't know if you will need mechanical thrombectomy or reversal agent, maybe, but you need to be ready for the two scenarios.

00:07:53: And as I was mentioning, the door to needle, the door to blood pressure lowering, it's the same.

00:08:01: Door to needle time when you need to reverse anticoagulation effect is very important, and you have to monitor it.

00:08:08: You have to monitor it the way you did it for IV from the lysis because you will notice in your own institution that numbers are not so great and I just did that with one of our colleagues in France in my hospital and I was really it was.

00:08:29: it was not really good because you know this is the way you you understand that you have logistical issues.

00:08:36: so here we are talking about reversal agent.

00:08:39: so you need to know where the reversal agent is.

00:08:42: and when you're talking about antidote like idarusisumab for example you you may not have it ready in your fridge in your stroke unit.

00:08:52: it may be in the trauma intensive care just three floors below.

00:08:59: So, you know, all these logistic issues are very important because every minute counts.

00:09:05: So, put aside the logistical issues, know where the product is, know what product you have in your own institution, and be ready for the patient who will arrive.

00:09:17: Then let's talk about the different agents.

00:09:20: First of all, we have to keep in mind that PCC, Protrombic, complex concentrate works.

00:09:30: I mean it works as well as it can in a severe ICH patients but it has been the gold standard as a comparator in all recent studies.

00:09:43: and we have to keep in mind that if you have PCC it's good, you have to use it.

00:09:47: The very important thing is that you have to use what you have.

00:09:52: For patients with Dabigatran, Idarusisumab is an excellent option, and we use it in my institution.

00:10:00: For patients with Factor XA inhibitor, we don't have endexanat alpha, so I do not have the experience of that.

00:10:11: What we can say from a literature perspective, and that's the main issue also with Idarusisumab and all the antidotes, is that Those studies were biological studies.

00:10:24: They were not clinical endpoint studies.

00:10:28: We have never clearly demonstrated that using an antidote or a reversal agent improves significantly morbidity and mortality compared to QCC.

00:10:46: It's the way it is because it's... because of the nature of an antidote, it doesn't require to be able to go on the market, it doesn't require a strong clinical endpoint.

00:11:00: So we are left with agents that seems to use from a biological perspective, but we are not sure that it has some impact on life and dependency.

00:11:13: So this is why the level of recommendation is very low.

00:11:19: in what we wrote in the most recent ESO guidelines.

00:11:24: And especially with endexanetalpha, you really have probably to clearly identify the patient and also it's fromboembolic risk because there's a cost to use this agent.

00:11:40: So for every single patient, it's a careful benefit-risk balance.

00:11:47: Are we very early on?

00:11:49: If we are very early on, it's worth taking the price of thromboembolic risk because it will have impact on the biological stabilization of coagulation and it will have some impact on the hematoma expansion.

00:12:06: If we are already late, ten hours or twelve hours, then the cost might not be the same because you will have a high risk of from buembolic risk without a lot of impact on hematoma expansion.

00:12:21: So the time window is very important.

00:12:24: Here I'm talking about agents that are very expensive, extremely expensive.

00:12:30: From a worldwide perspective, there are many patients that will not be able to benefit from this strategy.

00:12:38: So what else do we have?

00:12:39: So PCC, once again.

00:12:42: And there's the question of tranexamic acid.

00:12:47: For tranexamic acid, really for the moment, it's more raw than evidence-based.

00:12:54: We have very interesting data in all kinds of bleeding for sparta memory age.

00:13:00: polytrauma.

00:13:01: But for the moment, in the brain, we are not there yet.

00:13:05: And this is why there's this teach free trial, international trial.

00:13:11: So I know that in some countries, like in Germany, they can use tranexamic acid in current practice on a one by one case.

00:13:23: I think for the moment, it's better to use it in in a randomized controlled trial so that we will have soon and hopefully the answer.

00:13:35: All those trials on ICH and tranexamic acid, especially here, we were talking about patients who are treated and we forgot to tell it.

00:13:47: We were mentioning people who were having an ICH associated with anticoagulation use.

00:13:54: because they bleed more, they bleed longer, and their prognosis is quite poor.

00:14:03: When I'm talking about tranexamic acid, I'm switching to all ICH, even those patients who do not have anticoagulation.

00:14:16: It's a super interesting and I would say also super complicated situation and we definitely need more research, more evidence.

00:14:25: Definitely we need, as you suggest, very specific protocols and it's very interesting also how things work differently in different countries.

00:14:33: So thank you very much for your broad overview of everything.

00:14:38: Turning to the surgical approach, I would like to ask you a quite personal perspective.

00:14:43: I would like to know What's your point of view about the possibility of being treated also with a neurosurgery treatment for this patient in your experience?

00:14:51: When we should consider surgery and when we should avoid it?

00:14:57: So if we keep the line of our discussion, first we've discussed about the first step, which is to fight against hematoma expansion.

00:15:10: The second step in pathophysiology of ICH is really that blood in the brain, parenchyma, is not a good idea at all.

00:15:20: Because all the products of blood are triggering all kinds of toxic reactions on brain cells, inflammation, there's iron, etc.

00:15:34: So you really understand that blood has nothing to do there.

00:15:37: And ideally, we would like to take it out.

00:15:40: I would love to tell you, yes, I have a small thing and I put it in the brain and I suck it and oh, wow, that's done.

00:15:50: Unfortunately, it doesn't work like that in twenty twenty five.

00:15:55: And surgical approach of brain surgery in the acute face remains quite tricky.

00:16:03: from a technical perspective.

00:16:06: So the concept is good.

00:16:07: You have to go as quickly as possible in the brain to take the blood out.

00:16:15: But the reality is that all the types of devices that have been tried today do not have a significant impact on morbidity and mortality.

00:16:30: I mean, they may have some impact on mortality, but it's not enough.

00:16:34: I mean, we've been discussing that for stroke for a long time.

00:16:38: We need to have something that improves outcome, not only save life.

00:16:43: So in clinical practice, I consult the neurosurgical team when I have a young patient without pre-existing comorbidities and a lower bar ICH, which is more than thirty ML.

00:17:06: But I have to fight with my neurosurgical team.

00:17:09: Like everywhere, I think.

00:17:12: Like everywhere.

00:17:15: Because I think our concept still have to adjust.

00:17:19: But, you know, we had to discuss that with the interventional world in terms of mechanical front-back to me.

00:17:28: And this interplay with neurosurgery, I think, is what I... I think the most interesting in the multidisciplinary approach of ICH.

00:17:40: So we will figure out, but we really have to consider, yes, a young patient without comorbidities, third TML, low bar, but we have to do it quickly.

00:17:51: If we do it, it's quickly because if we wait twenty-four hours, the toxicity of blood in the brain parenchyma will have already happened.

00:18:04: and it will be too late.

00:18:05: Because I think neurosurgencies, some neurosurgencies, this strategy has only fighting against the mass effect concept.

00:18:17: But it's much more than just the mass effect.

00:18:20: It's really stopping a very toxic inflammatory cascade in the brain.

00:18:27: For deep ICH, unfortunately, I don't think we have anything that has demonstrated safety and efficacy.

00:18:34: and early September in the JAMA, the Mind Study was presented mainly targeting deep ICH and there's no statistically significant benefit of this strategy either.

00:18:55: In the next five years, surgery will be in.

00:18:58: I'm sure about it.

00:18:59: We just need to refine the timing and the technique.

00:19:05: So maybe looking ahead, one of the main evidence gap that we need is definitely to think about how to manage surgically also these patients.

00:19:14: Unfortunately, we don't have much time more, so I just want to ask you a last question.

00:19:19: Really?

00:19:20: Already?

00:19:21: You know, time is brain,

00:19:23: time is brain.

00:19:24: Super interesting to listen at you.

00:19:26: So if you had to give up one, just one.

00:19:29: practice message to a young neurologist in the emergency room facing an intracerebral hemorrhage.

00:19:34: What would this very unique practical message be?

00:19:40: Take your time.

00:19:42: So it might be contra-intuitive because I started with time is brain.

00:19:47: But beside time is brain, when I say take your time is that do not fall into the self fulfilling prophecy thinking that this patient will will die and you really have to take your time during the first twenty four forty eight hours.

00:20:06: just have active treatment and then you will be able to maybe more correctly assess the prognosis of those patients.

00:20:17: this is my my main Keep me safe.

00:20:20: I super like it.

00:20:21: I mean, it's like, you know, time is brain but take your time.

00:20:25: So thank you very much.

00:20:26: I think that now we can conclude this episode and I want to thank you for being here with us and thanks for the opportunity to moderate this session.

00:20:34: And I really recommend to hear also the next episode of EANcast, which are always very, very interesting and useful for everyone.

00:20:43: Thank you.

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