General vs Nongeneral Anesthesia for EVT in Patients With Large Core Strokes

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spk_0 This is José Merino, Editor in Chief of the Neurology Family of journals.

spk_0 The neurology podcast provides practical information to neurologists and other clinicians to help

spk_0 them provide better care for their patients.

spk_0 Thanks for listening and have a great week.

spk_0 Hello everyone, this is Andy Sutherland from the University of Virginia and I'm very

spk_0 excited to be speaking with my friend and colleague, Emre Sarage, who is the George M. Humphrey

spk_0 II Chair and Professor of Neurology at Case Western Reserve School of Medicine and

spk_0 Director of the Comprehensive Stroke Center at University Hospitals Cleveland Medical

spk_0 Center.

spk_0 For this week's neurology podcast, we're going to be discussing an article recently published

spk_0 in the journal titled General Versus Non-Generally Anesthesia for Endovascular thrombectomy

spk_0 in patients with large, core strokes.

spk_0 I was pre-specified secondary analysis of the select two trial.

spk_0 The select two trial was a prospective randomized trial that should benefit of endovascular thrombectomy

spk_0 in patients with large, core, schema strokes defined by aspect score of three to five on non-contrast

spk_0 head CT or an scheme core greater than or equal to 50 milliliters on CT perfusion study.

spk_0 Primary trial results were published in New England Journal in 2023 and today we're going

spk_0 to be discussing the results of this pre-specified analysis comparing patients who received

spk_0 a general versus non-general anesthesia in the trial.

spk_0 So, Amru, always great to have you on the podcast.

spk_0 Thanks for joining us.

spk_0 Thank you so much, Andy.

spk_0 It's a pleasure to be with you.

spk_0 Fantastic for our audience who may not keep up with this literature day to day in the realm

spk_0 of vascular neurology, acute stroke treatment.

spk_0 There have been numerous prior studies, meta-analyses of clinical trials that look at this sort

spk_0 of question of method of anesthesia in patients undergoing endovascular therapy for large,

spk_0 muscle occlusion stroke.

spk_0 One might ask, why is it important to readdress this in the select two randomized trial of patients

spk_0 with large, schema strokes, and specifically those with large, schema cores prior to the

spk_0 procedure?

spk_0 What is the relevance that led you and your team to want to pre-specify this as an important

spk_0 analysis?

spk_0 We are all approaching and charted territory until two or three years ago.

spk_0 It was for long believe that patients with large, schema core, those with low aspects

spk_0 early schema changes on the CAT scan aspects of 5 or less and just in brief the aspect is

spk_0 a major for good imaging profile or poor imaging profile, small core or large core in patients

spk_0 presenting with large, muscle occlusion.

spk_0 The prior trials showed benefit in small core excluded patients largely with aspects of

spk_0 5 or less and the core is measured on the perfusion images, those were areas that studied

spk_0 in research before and showed that patients who have regional, surploplethtflow less than

spk_0 30% as compared to a normal territory would have irreversible schema changes when you

spk_0 follow them on MRI at 72 hours.

spk_0 So those patients were excluded from prior trials or excluded from our practice largely.

spk_0 They were not part of guidelines, they were not part of practice guidelines at the different

spk_0 facilities because of inherited beliefs that they will not benefit.

spk_0 Rightfully the risk and benefit for a school is not well established because you have patients

spk_0 with large horse.

spk_0 Unlikely they will do as a natural history but also the potential benefit is not high

spk_0 because they have large skirts just having any large am I, very large subarachnoid

spk_0 hemorrhage.

spk_0 Prognosis is not good and the risk of hemorrhage transformation is high because you are

spk_0 reperfusing large area of them far.

spk_0 So now as we studied those in this elective trial and showed benefit of thrombectomy

spk_0 in this population as other 5 trials, randomized trials across the world reported benefit, the

spk_0 tension trial in Germany and Europe and Canada, the angel aspects in China, the rescue

spk_0 jet band limit in Japan, the last day trial in France and finally the Tesla trial which

spk_0 also showed either benefit in 5 trials or same direction with their protocol benefit in

spk_0 Tesla.

spk_0 Now those patients became part of the practice.

spk_0 They are being treated guidelines, been changed and the Australian guidelines been changed.

spk_0 The American Heart Association hopefully soon as as far as I know this is in advanced stages.

spk_0 This has been guidelines included these patients with aspects of 3 to 5, 0 to 24 hours.

spk_0 So when these become part of our practice we need to know how to approach these patients

spk_0 and anesthesia is one of the important goals that is associated with the procedure should

spk_0 I put the patient under general anesthesia or should I treat them with local or conscious

spk_0 sedation.

spk_0 That's the first part, the second part, while we showed benefit in this population we

spk_0 and others, the outcomes remained not as good as we want them.

spk_0 By nature these patients have very large strokes, you are not expecting the 60-70%

spk_0 independence rate or modified rankings, kilo-zero to 2 at 90 days.

spk_0 We observe somewhere around 20% rate but it's better than medical management of around

spk_0 7%.

spk_0 We observed 40% independence mobility in the amount of 3 which is excellent outcome.

spk_0 40% of patients with very large infarms being able to walk independently at 90 days as

spk_0 compared to doubling this in medical management.

spk_0 But we want to optimize these outcomes.

spk_0 We want this 40% to become 50 and 60.

spk_0 We want this 20% with the independent independence to be 30 and 40%.

spk_0 So it's these and similarly variables.

spk_0 The anesthesia, the blood pressure, be it at junk to therapies and reducing the edema

spk_0 being hemicraniactomy or being devices in different procedure approaches.

spk_0 These are the and silery variables that would help us optimizing the outcomes.

spk_0 That's why we thought this would be an important question to should lie down.

spk_0 And that makes complete sense, not only as you point out where these patients more or

spk_0 less excluded from prior trials so it's hard to extrapolate anything from how they would

spk_0 do based on our prior trial experience.

spk_0 There are legitimate biological, physiologic reasons why people with large schemes,

spk_0 coars large strokes would respond differently to different methods of anesthesia, may have

spk_0 different degrees of variability in their vital sign management and so forth both during

spk_0 and after the procedure.

spk_0 So naturally it is a very important question to readdress.

spk_0 Getting right to it, what were the main findings from this substudy that you all recently

spk_0 published?

spk_0 We asked the question, would patients with constestation or with general anesthesia have

spk_0 better association with clinical outcomes after thrombectomy.

spk_0 So this is only in the thrombectomy of a relation not in the medical management population

spk_0 when compared to each other on the 90 day outcome.

spk_0 And overall we found no difference.

spk_0 There was no difference in the modified rank and scale which is the function of an outcome

spk_0 at 90 days and we looked at one year because we have one year in and select two, no difference

spk_0 in independent emulation between general anesthesia and constestation.

spk_0 As you may imagine patients who receive general anesthesia take longer time to start the procedures

spk_0 of thromb randomization to doing the growing puncture.

spk_0 It was longer and was statistically significant but it was not associated with worse outcome.

spk_0 There was no difference in infarct volume and we limited the population to only the patients

spk_0 who got successful reperfusion, Antiqui to be more and there was no difference and we

spk_0 tried to look at interaction with the collateral status, stroke severity, the aspect score,

spk_0 there was no interaction.

spk_0 And going back the reason why we would think that one would be different than the others

spk_0 and I would say I was one of the people who thought that especially in this population

spk_0 patients with constestation will do better.

spk_0 These are large pore patients and you are worried that by doing general anesthesia the blood

spk_0 pressure will drop and you will lose collaterals and you will make what's already a large

spk_0 and far at large so the patients will end up doing worse.

spk_0 That's the hypothesis when we asked the question and actually to be fair while we did not

spk_0 specify constestation versus general anesthesia in the protocol we recommend that the size

spk_0 would do constestation and because it's not mandatory the size went on and did what they

spk_0 did and that would be my message to people in practice of throrours we ended up with 60%

spk_0 of the patients received in general anesthesia.

spk_0 So people did what they wanted to do and they perked to be right because there was no association

spk_0 between the type of anesthesia and the outcome.

spk_0 And you bring up a good point there.

spk_0 It does allow some flexibility and practice in folks who really work in this one way or

spk_0 the other and I agree with you it is a ought to probably lean towards your hypothesis leading

spk_0 up to the results of the study but it wasn't randomized.

spk_0 People did do what they wanted to do and so there's some inherent selection bias in that.

spk_0 How do you think these results will affect current practice, have they affected your own practice.

spk_0 And then what are some of those key limitations that we should keep in mind as we're interpreting

spk_0 the results of the substudy?

spk_0 Sure.

spk_0 As you mentioned we did not randomized and that on that anesthesia type.

spk_0 There were trials randomized on that anesthesia type back a few years ago that believe

spk_0 it can was that constestation or result in better outcome.

spk_0 It started with subanalyses from the Hermes showing better outcomes with constestation or

spk_0 local anesthesia as compared to general anesthesia.

spk_0 Then the randomized trials, the CS10 and stroke showed no difference.

spk_0 The Goliath and individual patient data metane analysis of four anesthesia general versus non-general

spk_0 showed better outcome with general anesthesia.

spk_0 From the paper that we published from, select and extend IA in a neurology a few years ago,

spk_0 a general anesthesia was associated with worse outcome, higher neurological worsening and

spk_0 worse effect in colatolous and that's why we had both his eyes and that's why we recommended

spk_0 and select to that patient that people do conscious sedation.

spk_0 Why the results are different?

spk_0 This is a major point that people should take into their practice, should take into their research.

spk_0 There is a difference between causation and association.

spk_0 A lot of times and we saw this over and over in blood pressure management.

spk_0 You come and do a subanalysis of what a prospective study in that patient with lower blood pressure

spk_0 ended up doing worse or better.

spk_0 That's and then you come and say lower blood pressure resulted in improved out.

spk_0 It is association. It is not causal relationship and that's why the trials that did intensive

spk_0 blood pressure management actually showed that patients do worse with intensive blood pressure

spk_0 management. It's the same concept when it comes to this.

spk_0 What we are learning and what we learned that the effect of endovascular thrombectomy and

spk_0 the perfusion is pretty strong and overcomes a lot of the ancillary variables around it.

spk_0 Of course we try to optimize everything but optimization does not always mean this way or the

spk_0 other. It might be your way that you do it best for the patients. If you are doing general

spk_0 anesthesia and you keep the patients not moving and your complications rate with pneumonia and other

spk_0 things are not high and you don't drop the blood pressure during the procedure then go ahead and do it.

spk_0 If you do conscious sedation better and you say my dissections rates are not too high and

spk_0 I'm not going to have complications then go ahead and do it. That is actually help because people don't

spk_0 need to change their protocol and say well for 15 years I have been doing conscious sedation and

spk_0 now you're coming and telling me to go ahead and do general anesthesia of rarsers. Not at all.

spk_0 As long as you and your team are comfortable with the procedure there was no difference in this

spk_0 specific variable when it comes to outcomes. When it comes to limitations and why I want people to

spk_0 when they read or when they see something say I'm not sure I agree with this. Of course this is

spk_0 non-randomized. I have news for you. I highly doubt that you will ever have this question being

spk_0 randomized. I just spent five minutes talking to you about causation and association so you should

spk_0 not be asking this question again in this manner because it's unlikely that you will find this

spk_0 type of answer that maybe when you have larger sample size you would know better because you will

spk_0 have more power but I will have my reservations on the conclusions because this is clear to me at

spk_0 this point. The multitude of these insular variables would have some sort of effect but them individually

spk_0 is unlikely unless there is something that we are systematically doing that would result in derailing

spk_0 the patient's outcomes and we are finding from select two and from prior studies that actually

spk_0 start the case with evidence. You bring up a number of good points there but importantly even if

spk_0 there is some selection bias as long as people are selecting based on their level of skill and comfort

spk_0 in reprefusing the brain it's a really strong message from the entire body of this work which is that

spk_0 the brain even in the setting of large ischemic core large strokes refusing that brain cures a lot

spk_0 of ills and washes out a lot of other ways that we try to optimize patient care and that's an

spk_0 important message to take away. It's really what you learned early in your residency and what you

spk_0 will continue to teach residents verbally until we get to a point that stroke is a plot in the blood

spk_0 vessel prevents low to the brain and the mainstay wise is and will always be reprefusion.

spk_0 Opening the blood vessel beats not opening the blood vessels eight days a week. The other variables

spk_0 important the nursing care the other things absolutely but spending resources just the messages

spk_0 go ahead and perfect what you do best and you will have good results better results than

spk_0 medical management in this population. Valid point and as you say I tell my residents the students

spk_0 all the time the brain doesn't care how it gets blood flow back as long as it happens and you do it

spk_0 as safely and quickly as possible that's a main message to make it which and all this ongoing

spk_0 richness data that come out of extent IA and now the select research trials what am I going to

spk_0 be interviewing you about on the podcast next what excites you most about to the next steps and

spk_0 it's always wonderful to be with you Andy and to look at the future so we have done a lot of

spk_0 analysis from select to it to be worth mentioning we are up to the 16th or the 17th daybar.

spk_0 If you important points to highlight we looked at one year outcomes and this was published in

spk_0 Lancet and patients continue to improve you have 20% of the patients who continue to improve

spk_0 between nine to days and one year very important that you are patient with your patients. Scott

spk_0 Castner published a very nice paper on Nellies and Hemicrania versus Noemicrania in early

spk_0 withdrawal of care and patients do worse when we think they will do worse so give the patients

spk_0 opportunity you don't expect patients who have a perfusion of very large core to be running

spk_0 down the whole way on day to rehabilitation works it may take longer and actually it opens the

spk_0 door is do we need to do longer than three months or outcomes up to one year no difference in

spk_0 hemicrania versus no hemicrania so don't be shy if you needed to do hemicrania for these patients

spk_0 and reliefing the pressure and giving them an opportunity no difference between men and women

spk_0 very important message the frailty and the woman of older age you may predict worse outcomes this

spk_0 was not the case close effectiveness in different healthcare system and that's important

spk_0 to the health care systems to adapt this in the United States in Europe and Australia

spk_0 different imaging modalities CT aspects perfusion which we mentioned originally no difference so

spk_0 this is refreshing that this became as well guidelines may take a little bit of time this became

spk_0 part of the practice you and I can't attest to that time many people already change their

spk_0 because they see the evidence so next is we a few things that we still need to understand and

spk_0 to optimize things the treatment benefit and this population what was driven by a reperfusion

spk_0 part of it decreasing final and viral in part of it what is the role of cerebral edema what is

spk_0 one plus two plus three equals percentage of the improvement may not be from a single trial may

spk_0 need the collected collective data and it's good to share with your audience that the PIs for

spk_0 all the doctor randomized trials met agreed a few months ago to proceed with a meta-analysis

spk_0 of this population to shed light on the subgroups because there's no single trials power to

spk_0 tell you is it beneficial more than 150 you have a higher limit what about the Erlund versus

spk_0 Slate wonder even the question that we've just discussed about anesthesia and blood pressure and

spk_0 all of that so this data will be presented in its first shape at the World Stroke Conference in

spk_0 Barcelona next month the Atlas meta-analysis and will be again reread all of the images by

spk_0 independent core lab with Dr. Campbell and in Melbourne and then we'll probably represent the data

spk_0 and publish it to shed light and look at all of these subgroups how can we optimize the patients how

spk_0 can we enhance the outcomes for this population to get patients because this is why research is

spk_0 done it's not just to answer my curiosity or yours is to bring the questions that will bring a new

spk_0 treatment to patients and new populations to get patients back to their family into the society

spk_0 sound healthy and probably productive part of the society I believe that you're also going to be

spk_0 looking at patients who present after 24 hours from last know that is still an area where there's

spk_0 some echo poise these patients that present very late from time of last know correct me if I'm

spk_0 wrong this will be the select late trial that we're hoping to get off the ground and learn some from

spk_0 so for a long time we invest in nature of human being operated on having a line in the sand for

spk_0 time patients with TBA first three hours and four and a half hours from back to me first six hours

spk_0 than 24 hours but what about the population that may present beyond 24 hours and might still have

spk_0 viable brain tissue to be treated we're looking at this in this elect late trial and hopefully

spk_0 we partner on this with you in the population in the University of Virginia currently this is

spk_0 another uncharted territory so size is done what about late what about time can we open the door

spk_0 for those patients who may present two days from their last well more than 24 hours and if this

spk_0 shown to be positive and we published the cohorts multi center international study about this

spk_0 and showed potential benefit so we're known randomizing the patients if these patients would

spk_0 benefit this would change a lot this would change our assistance of care approach transfer

spk_0 and patients all of that but it's all would be for the good of the patients and yeah this might be

spk_0 a few years away it's a grant from the patient center to outcome and I'm really happy to

spk_0 partner with you and other colleagues on this to bring an answer to this important question

spk_0 fantastic that's a great message to end on and certainly sounds like there's a lot of ongoing

spk_0 collaboration that will lead even better analysis from these collective data within that atlus

spk_0 consortia and I will be excited to hear about that and perhaps we will bring you back on to tell

spk_0 us about that once it's presented at world's shirt congress next month but in the meantime I want

spk_0 to think again my colleague Amru Saraj for joining us with the podcast is discuss this paper again

spk_0 titled general versus non-general anesthesia for end of asco thrombone that to me and patients with

spk_0 large core strokes a pre-sumissified secondary analysis of the select to trial seek out the

spk_0 main paper in the neurology journal and look forward to this and other podcasts on the topic and

spk_0 really thank you so much again for joining us this is tacy claudier podcast editor if you've enjoyed

spk_0 the podcast please take a few moments to subscribe rate and review the neurology podcast through apple

spk_0 podcasts google podcast spotify or wherever you listen and remember you can always head to neurology.org

spk_0 exlash podcast for a full list of past episodes where you can also search by keyword in your podcast

spk_0 app running neurology specific topics you want to learn about

General vs Nongeneral Anesthesia for EVT in Patients With Large Core Strokes

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