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Episode 87: Master Class - Hyperacute Management of Intracerebral Hemorrhage with Stephan Mayer

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Description

Welcome to the Master Class Series where we will learn from the masters in Neurocritical Care.

On this episode, learn from Stephan Mayer, MD, FCCM, FNCS Director of Neurocritical Care and Emergency Neurology Services for Westchester Medical Center Health System and Professor of Neurology and Neurosurgery at New York Medical College as he discusses Hyperacute Management of Intracerebral Hemorrhage.

The NCS Podcast is the official podcast of the Neurocritical Care Society.

Contributors

  • Stephan A. Mayer, MD, FCCM

    William T. Gossett Endowed Chair of Neurology
    Henry Ford Health System
    Stephan Mayer is Chair of Neurology for the Henry Ford Health System in Detroit. He previously served as director of Neurocritical Care for the Mount Sinai Health System in New York and director of the Neurological Intensive Care Unit at Columbia University College of Physicians and Surgeons in New York. Dr Mayer earned his medical degree from Cornell University Medical College. He completed a residency in neurology and a fellowship in critical care neurology at the Neurological Institute of New York, Columbia-Presbyterian Medical Center. He is board certified in neurology and a founding member and past president of the Neurocritical Care Society. Dr Mayer has published more than 230 original research articles, 180 review articles, and 340 abstracts, and he has written 7 books, and co-edited the most recent edition of Merritt’s Textbook of Neurology. He was principal investigator of the FAST Trial, a worldwide multicenter clinical trial evaluating ultra-early hemostatic therapy for brain hemorrhage, and he served as principal investigator of the NIH-funded New York Presbyterian Hospital hub of the Neurological Emergencies Treatment Trials (NETT) network. His work in helping victims of severe brain injury has been featured in The Wall Street Journal and the book Cheating Death by CNN medical correspondent Dr Sanjay Gupta.

  • Jon Rosenberg, MD

    Jon Rosenberg is an Assistant Professor of Neurology and Neurosurgery at Westchester Medical Center New York Medical College and Associate Program Director of the Neurocritical Care Fellowship at Westchester Medical Center. 

  1. 00:00:18
    Welcome NCS podcast listeners, this is
  2. 00:00:21
    John Rosenberg, I'm a neurointensivist
  3. 00:00:23
    at Westchester Medical Center, part of
  4. 00:00:25
    the NCS podcast series, here to
  5. 00:00:28
    interview Dr. Stefan Mayer about the
  6. 00:00:31
    hyper keep management of interestable
  7. 00:00:33
    hemorrhage, what he likes to call code
  8. 00:00:35
    ICH. So welcome Stefan. Thank you,
  9. 00:00:41
    John, and for the listeners, if you
  10. 00:00:43
    don't know, I am also at Westchester
  11. 00:00:46
    Medical Center, about 25 miles north of
  12. 00:00:49
    Manhattan. We're also affiliated with
  13. 00:00:53
    New York Medical College, and we work
  14. 00:00:55
    together in the same ICU. It's my
  15. 00:00:59
    pleasure to be here. So Stefan, give
  16. 00:01:03
    me some background about this issue and
  17. 00:01:06
    the issue at hand here. And why does
  18. 00:01:08
    this deserve our attention as
  19. 00:01:09
    intensivists? Sure, absolutely Well,
  20. 00:01:13
    as you know, stroke care is a team
  21. 00:01:16
    sport. and it's truly a continuum of
  22. 00:01:19
    care that begins in the pre-hospital
  23. 00:01:22
    setting and extends all the way out
  24. 00:01:24
    through rehabilitation and recovery.
  25. 00:01:27
    Certainly emergency care and the
  26. 00:01:31
    interventions that we perform these days
  27. 00:01:34
    and the transition into the ICU is this
  28. 00:01:39
    perfect kind of explosion of activity
  29. 00:01:42
    right there because minutes count, time
  30. 00:01:44
    is brain
  31. 00:01:47
    The reason I think that this is a really
  32. 00:01:49
    important topic is because in my
  33. 00:01:52
    personal opinion, ICH
  34. 00:01:56
    has really gotten the short end of the
  35. 00:01:58
    stick by us as a stroke community with
  36. 00:02:03
    when you compare to all of the focus and
  37. 00:02:06
    attention and discipline that we perform
  38. 00:02:12
    in the care of acute ischemic stroke,
  39. 00:02:14
    right? Everything is measured. There
  40. 00:02:17
    are many, many quality metrics and,
  41. 00:02:20
    you know, all these stroke measures and
  42. 00:02:22
    everything else and we're all held to be
  43. 00:02:24
    accountable for all the timelines that
  44. 00:02:28
    matter so much, right? 19 million
  45. 00:02:31
    neurons die a minute in an LV of stroke.
  46. 00:02:35
    And then you turn to ICA and it's like
  47. 00:02:37
    crickets. Like there's two guidelines,
  48. 00:02:42
    you know, parameters you weren't
  49. 00:02:43
    supposed to follow You and ICA score,
  50. 00:02:46
    and if somebody's in a cragulating,
  51. 00:02:48
    reverse them. But nobody talks about
  52. 00:02:52
    what to reverse them with, or even more
  53. 00:02:55
    importantly, how quickly to reverse
  54. 00:02:57
    them. There's no emphasis on this in
  55. 00:03:00
    our comprehensive or primary stroke
  56. 00:03:01
    centers. And that's what we want to try
  57. 00:03:03
    to change with the concept or platform,
  58. 00:03:06
    if you will, of code ICH And I know
  59. 00:03:08
    you've advocated this in both informal
  60. 00:03:13
    settings and. you know, society
  61. 00:03:15
    meetings and also in a recent paper. So
  62. 00:03:18
    maybe, let's start. Tell us a little
  63. 00:03:19
    bit about kind of the bundle care aspect
  64. 00:03:22
    and how we can, it basically improve
  65. 00:03:25
    outcomes with interest ripple hemorrhage.
  66. 00:03:27
    Sure. So stroke care in general, a
  67. 00:03:31
    long time ago, was more like serial
  68. 00:03:34
    processing of different steps of care.
  69. 00:03:38
    And, you know, there was a seed change
  70. 00:03:40
    culminating in Helsinki protocol where,
  71. 00:03:43
    you know, people that practice stroke
  72. 00:03:50
    care said, you know what, getting a
  73. 00:03:54
    chest x-ray and a stroke patient is
  74. 00:03:54
    stupid. And it's not essential to the
  75. 00:03:54
    mission of what we're trying to do in
  76. 00:03:55
    the earliest hours. Putting somebody
  77. 00:03:58
    out of an ambulance onto, you know, a
  78. 00:04:01
    hospital bed in the ER and then taking
  79. 00:04:03
    them, putting them back on a rolling
  80. 00:04:05
    gurney is stupid. It doesn't make sense.
  81. 00:04:07
    Go directly to CT scan in this concept
  82. 00:04:11
    of parallel processing, right, to
  83. 00:04:13
    multiplex - activities are all occurring
  84. 00:04:16
    in parallel as opposed to serial
  85. 00:04:19
    processing, right? So cut the fat
  86. 00:04:22
    parallel processing. And of course, in
  87. 00:04:25
    critical care in general now, whenever
  88. 00:04:27
    we're performing multiple tasks
  89. 00:04:30
    simultaneously, we like the term bundle.
  90. 00:04:33
    Everyone uses the term bundle. And
  91. 00:04:36
    there, you know, I think AIS emergency
  92. 00:04:39
    care is pretty well bundled And I don't
  93. 00:04:42
    think we've given enough thought to what
  94. 00:04:45
    should the care, the emergency care
  95. 00:04:47
    bundle be or look like for
  96. 00:04:50
    interest-freeable hemorrhage. And
  97. 00:04:52
    that's what we set about my co-authors
  98. 00:04:55
    and I in the manuscript that we've
  99. 00:04:57
    recently completed and is currently
  100. 00:04:58
    under review. We, as an independent
  101. 00:05:02
    group of what you'd call ICH people,
  102. 00:05:05
    wanted to examine the evidence and
  103. 00:05:09
    figure out now, right, in the summer
  104. 00:05:10
    of 2023.
  105. 00:05:16
    What's ready for prime time? So
  106. 00:05:18
    basically, what you're advocating is
  107. 00:05:20
    when patients come with an ICH, we want
  108. 00:05:22
    to bundle care to reduce hematoma
  109. 00:05:24
    expansion, to reduce peri-hematoma
  110. 00:05:26
    edema and to improve mortality. So why
  111. 00:05:28
    don't we go through, tell us a little
  112. 00:05:29
    bit about how we can do this, and we
  113. 00:05:31
    can maybe start with blood pressure.
  114. 00:05:33
    Tell us a little about your thoughts
  115. 00:05:34
    about the hypercube blood pressure
  116. 00:05:36
    management in ICH. Yeah, sure. And
  117. 00:05:39
    then for those that are interested is
  118. 00:05:41
    when this manuscript comes out, it's
  119. 00:05:43
    called code ICH, a call to action. So
  120. 00:05:47
    let's start with blood pressure. ICH
  121. 00:05:49
    produces some of the high blood
  122. 00:05:51
    pressures encountered in all clinical
  123. 00:05:53
    medicine. Well, of course, we have
  124. 00:05:55
    the two big trials, right? ICH and
  125. 00:05:57
    interact indicating no harm for sure,
  126. 00:06:04
    maybe a weak benefit in terms of
  127. 00:06:07
    hematoma expansion, possibly in one of
  128. 00:06:11
    the trials, a weak signal towards.
  129. 00:06:13
    Some improve rank and shift, although
  130. 00:06:15
    neither study hit the primary clinical
  131. 00:06:17
    outcome under modified rank and scale.
  132. 00:06:20
    What you may not be aware, though, is
  133. 00:06:22
    that subsequent studies, secondary
  134. 00:06:26
    analyses, have gone on to show that
  135. 00:06:28
    when you look at patients treated within
  136. 00:06:31
    two hours, because these right
  137. 00:06:33
    understand these studies study blood
  138. 00:06:36
    pressure intervention out to as late as
  139. 00:06:38
    six hours. We know that in
  140. 00:06:40
    non-quagulate pathic patients,
  141. 00:06:42
    hematomic expansion is pretty much done
  142. 00:06:44
    at three hours. So to really make a
  143. 00:06:47
    difference, it has to happen in that
  144. 00:06:49
    earliest window as quickly as possible.
  145. 00:06:52
    In the sub-analyses, earlier
  146. 00:06:54
    intervention, such as within two hours
  147. 00:06:57
    of symptom onset, you start to see a
  148. 00:06:59
    stronger signal with less hematomic
  149. 00:07:02
    expansion and a stronger signal in terms
  150. 00:07:04
    of the clinical outcomes. Again, the
  151. 00:07:08
    references are all gonna be in the
  152. 00:07:09
    manuscript So our thinking is, Um, if
  153. 00:07:15
    everyone controls elevated blood
  154. 00:07:18
    pressure anyway, right, um, they're,
  155. 00:07:22
    they're, you know, right, they do,
  156. 00:07:24
    right. Why not perform it as quickly as
  157. 00:07:27
    possible. It can only work better If
  158. 00:07:32
    you're going to give you faster, go it,
  159. 00:07:33
    right, in terms of the hope that you
  160. 00:07:35
    might be able to tamp down active
  161. 00:07:38
    bleeding and hematomic expansion.
  162. 00:07:40
    There's no, there's no, right, it's
  163. 00:07:42
    forced to think that it would be more
  164. 00:07:44
    helpful waiting and letting the blood
  165. 00:07:46
    pressure be extremely high. So if
  166. 00:07:48
    you're going to do it, like go big or
  167. 00:07:49
    go home and do it as soon as possible
  168. 00:07:52
    You also examine some of the data
  169. 00:07:54
    looking at, well, how low do you go,
  170. 00:07:56
    which of course is what interact and
  171. 00:07:58
    attach wanted to do. And we're, we as
  172. 00:08:02
    a group are not making a firm judgment
  173. 00:08:06
    about, you know, the definitive
  174. 00:08:08
    evidence is that everyone should be
  175. 00:08:10
    controlled down to 140 or 130 to 150 or
  176. 00:08:13
    whatever.
  177. 00:08:16
    We're not saying, we're claiming that
  178. 00:08:20
    this is absolutely the right thing to do
  179. 00:08:22
    for all people. I think those issues
  180. 00:08:23
    have to be individualized. There is
  181. 00:08:26
    data that with really high blood
  182. 00:08:27
    pressures you can do harm going down too
  183. 00:08:29
    far too fast. So somebody showing up at
  184. 00:08:32
    230, you probably don't want to lower
  185. 00:08:34
    that blood pressure down to 140 systolic
  186. 00:08:37
    within one hour of hitting the door But
  187. 00:08:39
    we do think that the science indicates
  188. 00:08:42
    that there's only more potential benefit
  189. 00:08:46
    if you're lowering blood pressure to do
  190. 00:08:48
    it as quickly as possible, like we do
  191. 00:08:50
    with TPA. So we're basically in the
  192. 00:08:54
    code ICH manifesto, if you will, we're
  193. 00:08:57
    saying we think it's time as a global
  194. 00:09:00
    quality metric to strive to initiate
  195. 00:09:05
    blood pressure reduction, regardless of
  196. 00:09:08
    what agent or target you're going for
  197. 00:09:10
    within 60 minutes of arriving in the ED.
  198. 00:09:13
    an acute
  199. 00:09:16
    ICH, right? That's basically the idea.
  200. 00:09:21
    We just don't see any, like, it's time,
  201. 00:09:24
    right? In addition to the hyper acute
  202. 00:09:26
    lowering of blood pressure, I'll just
  203. 00:09:28
    say, I think I'll use the word signal.
  204. 00:09:30
    I think there's a lot of, there's been
  205. 00:09:32
    some signal in both of these post hoc
  206. 00:09:33
    analysis in other studies showing not
  207. 00:09:35
    just the actual number, but the, it's
  208. 00:09:39
    not just the actual number, but the
  209. 00:09:42
    fluctuation, limiting the fluctuations
  210. 00:09:44
    of blood pressure may be beneficial.
  211. 00:09:46
    And that's similar to, I think that's
  212. 00:09:47
    reflected in the, the new AHA
  213. 00:09:49
    guidelines or, yeah,
  214. 00:09:52
    you want accuracy and stability. Now,
  215. 00:09:55
    in my own practice, I think that
  216. 00:09:58
    nichardipine or clavidipine should be
  217. 00:09:59
    the first line agent in every stroke
  218. 00:10:04
    patient where you're actively lowering
  219. 00:10:05
    blood pressure, right, whether it's
  220. 00:10:07
    AIS or SAH or ICH.
  221. 00:10:11
    I think that's the easiest way to get
  222. 00:10:12
    with the stability. We as a group
  223. 00:10:15
    though for code ICH, we don't we didn't
  224. 00:10:18
    think that that is ready today to be
  225. 00:10:20
    like at the level of a quality metric
  226. 00:10:22
    right but if you're a center that gets
  227. 00:10:25
    around to starting a blood pressure
  228. 00:10:27
    lowering agent and acutely hypertensive
  229. 00:10:29
    ICH patient five or six hours later
  230. 00:10:32
    that's that you know that doesn't
  231. 00:10:35
    wouldn't stand to
  232. 00:10:38
    represent quality care it's not meaning
  233. 00:10:42
    to stay care. Tell us a little bit
  234. 00:10:44
    about perihema management of
  235. 00:10:45
    perihematoma edema hemo inflammation
  236. 00:10:48
    this is kind of one of the banes of
  237. 00:10:50
    neurointensivists how do we how do we
  238. 00:10:53
    manage this do we have any tools in and
  239. 00:10:54
    what were the kind of metrics we should
  240. 00:10:56
    strive for? Yeah yeah we examined that
  241. 00:10:59
    as well as you know you know i-deaf was
  242. 00:11:03
    negative that for ox i mean a variety of
  243. 00:11:07
    neuroprotective agents have been tested
  244. 00:11:09
    in i-c-h to reduce peri hematoma tissue
  245. 00:11:12
    injury, they've all struck out. We
  246. 00:11:15
    have basically the boas osmotherapy
  247. 00:11:18
    technique and the hyperventilation
  248. 00:11:20
    technique.
  249. 00:11:22
    The fact of the matter is though, like
  250. 00:11:24
    if most I see each patient, so many of
  251. 00:11:27
    them don't really need, the edema
  252. 00:11:29
    builds up over time. So you're really
  253. 00:11:32
    hanging mandatory pushing hypertonics in
  254. 00:11:35
    the first hour, 'cause we're focusing
  255. 00:11:37
    really on a hyper acute phase, the
  256. 00:11:39
    emergency phase, the first hour or two.
  257. 00:11:42
    You're basically, if you feel they need
  258. 00:11:45
    it, this is basically a temporizing
  259. 00:11:47
    measure for definitive surgical
  260. 00:11:49
    intervention, right? If it's at that
  261. 00:11:51
    point, in other words, you gotta have
  262. 00:11:52
    a lot of shift already, showing up with
  263. 00:11:55
    a lot of shift. And everybody's gonna
  264. 00:11:58
    use those agents, but again, we just
  265. 00:12:02
    didn't feel that
  266. 00:12:05
    given the potential of other
  267. 00:12:07
    interventions that we can do, We just
  268. 00:12:11
    didn't feel that it was kind of ready.
  269. 00:12:13
    Maybe we'll go down the road, but at
  270. 00:12:16
    this point, we didn't think it was
  271. 00:12:17
    really ready to be proposed as a
  272. 00:12:20
    national or worldwide standardized
  273. 00:12:24
    quality metric, like giving nanotol
  274. 00:12:26
    within one hour. And remember, it's
  275. 00:12:29
    only gonna apply to the smaller subset
  276. 00:12:31
    of people that are already in deep,
  277. 00:12:32
    deep trouble when they show up. The
  278. 00:12:35
    greatest thing you thought. We also
  279. 00:12:36
    though, John, I will tell you along
  280. 00:12:39
    those lines, 'cause we're touching on
  281. 00:12:40
    surgical intervention. We did think
  282. 00:12:43
    hard about what if we proposed, if a
  283. 00:12:47
    ventricular ostomy is placed, that
  284. 00:12:54
    it should be placed within a certain
  285. 00:12:55
    timeframe. And that's a really good
  286. 00:12:55
    thought. And maybe that will become an
  287. 00:12:57
    ICH quality metric one day. But we
  288. 00:13:03
    didn't have enough consensus around it
  289. 00:13:04
    to propose that one here in the summer
  290. 00:13:06
    of 2023 So it really, it sounds like
  291. 00:13:09
    our. a management of perihemotoma edema
  292. 00:13:12
    is quite limited, really just acute
  293. 00:13:15
    hydrostatic forces using, we can use
  294. 00:13:17
    hypertonics to manage the acute
  295. 00:13:19
    hydrostatic pressure, but like you
  296. 00:13:21
    mentioned earlier, all the other trials
  297. 00:13:23
    with kind of in the subacute stage with
  298. 00:13:25
    all the pro-inflammatory milieu that may
  299. 00:13:28
    worsen peritone edema. All those kind
  300. 00:13:30
    of iron scavenger trials have all been
  301. 00:13:32
    negative unfortunately. When we talk a
  302. 00:13:35
    little bit about
  303. 00:13:39
    hemostatic therapy and non-coagulopathic
  304. 00:13:40
    ICH. So we will get to how to reverse
  305. 00:13:43
    anti-platelets and how to reverse blood
  306. 00:13:45
    thinness. But what about, tell us a
  307. 00:13:46
    little bit about the consensus, your
  308. 00:13:49
    consensus about how do we,
  309. 00:13:52
    what type of hemostatic agents we can
  310. 00:13:54
    use if any of you should use an
  311. 00:13:56
    non-coagulopathic ICH. Right, so in
  312. 00:13:59
    1998,
  313. 00:14:02
    I had a dream. I was Martin Luther King
  314. 00:14:05
    wannabe and found out about this. very
  315. 00:14:09
    interesting age of recombinant,
  316. 00:14:10
    activated factor 7A, approved for use
  317. 00:14:14
    as a kind of a replacement for factor 8,
  318. 00:14:17
    and hemophiliacs who have antibodies
  319. 00:14:20
    against factor 8 replacement therapy,
  320. 00:14:22
    so it doesn't work. 7A is a true
  321. 00:14:26
    pro-coagulant. It, if you inject a
  322. 00:14:29
    pharmacologic dose intravenously, will
  323. 00:14:31
    literally instantly activate a normal
  324. 00:14:34
    coagulation system into a supercharged
  325. 00:14:37
    coagulation system that will act where
  326. 00:14:40
    it sees exposure of tissue factor or
  327. 00:14:43
    activated platelets, and it will drive
  328. 00:14:46
    rapid formation of fiber and clot at the
  329. 00:14:48
    site of vascular injury. And the clots
  330. 00:14:51
    that result are actually abnormally
  331. 00:14:54
    dense and supernormally resistant to
  332. 00:14:59
    counter-fibrillitic forces that
  333. 00:15:02
    naturally occur So 7A, as you know,
  334. 00:15:05
    was tested in the trials that I ran.
  335. 00:15:08
    published in 2005 and 2008. The 2B was
  336. 00:15:12
    positive, the same study, same time
  337. 00:15:15
    frame, the phase three fast trial was
  338. 00:15:17
    negative. Since then, there have been
  339. 00:15:20
    attempts to look at 7A and in a rich
  340. 00:15:22
    cohort of ICH patients thought to be at
  341. 00:15:25
    high risk for human-to-home expansion
  342. 00:15:27
    with CT spot sign, they were treated
  343. 00:15:30
    too late, basically. There were
  344. 00:15:32
    attempts to look at tranexamic acid in
  345. 00:15:36
    the same way, but tranexamic acid is
  346. 00:15:38
    not a pro-coagulant. It is actually an
  347. 00:15:42
    antifibrillator. So it'll help support
  348. 00:15:45
    a clot that's been formed, but it's not
  349. 00:15:47
    gonna supercharge the formation of a
  350. 00:15:49
    clot in the first place. And that
  351. 00:15:51
    brings us to the ongoing fastest trial,
  352. 00:15:54
    which is NIH funded,
  353. 00:15:58
    enrollment. We're now doing really well.
  354. 00:16:00
    I think we're up to about 200 patients
  355. 00:16:04
    enrolled out of a totally expected
  356. 00:16:06
    steady population of. 900 about. It's
  357. 00:16:10
    two arms. It's the 80 micro kilogram
  358. 00:16:12
    dose of 7a versus placebo.
  359. 00:16:15
    Interestingly, the best enrollment so
  360. 00:16:16
    far has been in China. And the study is
  361. 00:16:20
    ongoing. And so I think there's a lot
  362. 00:16:23
    of optimism that maybe in two years when
  363. 00:16:25
    we get that final result, we're going
  364. 00:16:28
    to have an emergency treatment for your
  365. 00:16:31
    standard run of the mill
  366. 00:16:33
    non-quagulopathic ICH. Why? Why would
  367. 00:16:36
    this work? Because the onset to needle
  368. 00:16:38
    time in fastest is two hours, not four
  369. 00:16:43
    hours, right? And we're leveraging
  370. 00:16:47
    mobile stroke units in places where they
  371. 00:16:50
    are and focusing on centers that have a
  372. 00:16:54
    very high volume of ICH coming in
  373. 00:16:57
    through their ED through the front door.
  374. 00:17:00
    Sure, so
  375. 00:17:03
    if I can summarize basically with regard
  376. 00:17:04
    to hemostatic agents. So factor 7A in
  377. 00:17:07
    the largest trial, we have to date the
  378. 00:17:08
    FAST trial, there was no, there was no
  379. 00:17:10
    benefit seen. However, the postdoc
  380. 00:17:12
    analysis showed that there was a
  381. 00:17:13
    suggested hyper acute administration
  382. 00:17:15
    within two hours, factor seven
  383. 00:17:17
    administration within two hours may
  384. 00:17:19
    reduce hematomic expansion, which is
  385. 00:17:21
    being, then that hypothesis now being
  386. 00:17:24
    tested in the fastest trial. Yeah, let
  387. 00:17:26
    me, let me just, both the 2B and the
  388. 00:17:28
    FAST trial, both demonstrated a similar
  389. 00:17:31
    strong effect, hemostatic effect of
  390. 00:17:34
    reducing hematomic expansion, it showed
  391. 00:17:37
    that the clinical outcomes played out
  392. 00:17:38
    really in favor of active treatment and
  393. 00:17:41
    the 2B, but it didn't end the phase
  394. 00:17:44
    three fast trial. Well, basically
  395. 00:17:47
    owing to the fact that the size of your
  396. 00:17:50
    hematoma you end up with isn't the only
  397. 00:17:52
    thing that determines outcome after
  398. 00:17:53
    stroke. You have all your preexisting
  399. 00:17:55
    comorbidities and medical complications
  400. 00:17:58
    and things like that So other
  401. 00:18:00
    modifications we've made, we have a
  402. 00:18:03
    tighter age cut off and I think it's 75.
  403. 00:18:06
    gimme, and we've excluded people that
  404. 00:18:08
    are showing up with large amounts of IVH
  405. 00:18:11
    at baseline, which we didn't do
  406. 00:18:13
    previously, because once you've bled
  407. 00:18:15
    that much, right, they kind of cats
  408. 00:18:17
    out of the bag, right? So they're not
  409. 00:18:19
    going to be able to benefit as well. So
  410. 00:18:21
    this was all modeled on that
  411. 00:18:22
    pre-existing data. And you know, we
  412. 00:18:25
    think we've got a strong shot to
  413. 00:18:28
    show that at least in that type of
  414. 00:18:31
    patient The best way to predict who's
  415. 00:18:34
    going to bleed, continue if you need to
  416. 00:18:36
    have an expanded chin, is how early you
  417. 00:18:38
    get that baseline CT.
  418. 00:18:41
    So let's talk a little about
  419. 00:18:42
    anti-quagulation reversal. I know it's
  420. 00:18:44
    a subject near and dear to your heart.
  421. 00:18:47
    So just to walk us through, why don't
  422. 00:18:50
    we know for, I guess, summarize for
  423. 00:18:52
    the audience for vitamin, you know,
  424. 00:18:53
    for patients on vitamin K antagonists.
  425. 00:18:55
    We typically use, we use four-factor
  426. 00:18:57
    PCC, just been shown to be superior to
  427. 00:19:00
    FFP. And then for reversal of direct
  428. 00:19:03
    lobbying and barriers such as. that we
  429. 00:19:05
    use, there are Susan Mabra, Praxabind,
  430. 00:19:08
    after the reverse AD trial. Why don't
  431. 00:19:10
    we talk a little bit about factor 10A
  432. 00:19:13
    reversal? Yep, happy. Or that should
  433. 00:19:16
    say a 10A inhibitor reversal. Tell me
  434. 00:19:18
    about that. I'm gonna disclose, John,
  435. 00:19:23
    that I'm NIH-funded for my work on the
  436. 00:19:27
    fastest trial, and I have received some
  437. 00:19:29
    relatively small consulting fees from
  438. 00:19:31
    AstraZeneca, which currently is the
  439. 00:19:36
    maker of Andexa, which is the designer
  440. 00:19:40
    drug meant, designed specifically to
  441. 00:19:43
    reverse anticoagulation
  442. 00:19:50
    from a factor 10A inhibitor, like a
  443. 00:19:52
    Pixabena-Rivor-Oxaban. Now, up till
  444. 00:19:55
    now, the thing is that the data for
  445. 00:19:58
    Andexa in reversing 10A anticoagulation
  446. 00:20:01
    is all based on coagulation assays.
  447. 00:20:07
    There's been no great head-to-head data
  448. 00:20:11
    with four-factor PCCs, which are the
  449. 00:20:13
    other alternative treatment that centers
  450. 00:20:16
    have used. There's been case series
  451. 00:20:21
    showing reasonable hemostasis. There's
  452. 00:20:24
    one larger European study which took two
  453. 00:20:27
    different sets, but basically,
  454. 00:20:30
    anticoagulated with 10A inhibitors, you
  455. 00:20:32
    know, not randomized, different sites,
  456. 00:20:34
    different time apex even, but showing
  457. 00:20:38
    better radiographic outcomes, a little
  458. 00:20:40
    bit less hematomic expansion in the
  459. 00:20:42
    index of treated patients compared to
  460. 00:20:43
    the four-factor PCCs. But the big news,
  461. 00:20:48
    if you haven't been made aware, just on
  462. 00:20:53
    Monday of this week, I think, a press
  463. 00:20:56
    release was announced that the ANEXA-I
  464. 00:20:59
    trial has been stopped by the Data
  465. 00:21:03
    Safety Monitoring Committee. And the
  466. 00:21:05
    reason it was stopped was that there was
  467. 00:21:08
    superior results and favorable outcome
  468. 00:21:11
    in the index arm compared to usual care
  469. 00:21:15
    and I'm making air quotes, but usual
  470. 00:21:18
    care most of these sites as we know was
  471. 00:21:20
    was a four factor PCC. We know of
  472. 00:21:22
    nothing more than that. Right. None of
  473. 00:21:25
    the data has been released But we do
  474. 00:21:27
    know that the safety committee did stop
  475. 00:21:30
    the trial. And so we will very eagerly
  476. 00:21:33
    look to see that data when it comes out.
  477. 00:21:39
    That's that's the issue of of agent in
  478. 00:21:42
    this in the code ICH call to action
  479. 00:21:45
    paper. We're agnostic about which agent
  480. 00:21:49
    you choose to use We're staying out of
  481. 00:21:52
    it. And what you should know is it's
  482. 00:21:54
    already a whole bunch of guidelines,
  483. 00:21:55
    you know, on, you know, European US
  484. 00:22:00
    guidelines on what to give to reverse
  485. 00:22:03
    and for ICH. the language in both of
  486. 00:22:06
    these sets of guidelines is used to most
  487. 00:22:08
    effective agent available. Thank you,
  488. 00:22:12
    Stephon, for that great summary.
  489. 00:22:16
    As mentioned, all the trials to date
  490. 00:22:19
    comparing and DEXA versus four-factor
  491. 00:22:22
    PCC are really limited. They compared
  492. 00:22:24
    different samples, propensity-matched
  493. 00:22:27
    analysis. Yeah, they're not really
  494. 00:22:29
    trials, John, right? They're sort of
  495. 00:22:31
    like different data sets Patchwork
  496. 00:22:34
    comparison. That's right. Maybe the
  497. 00:22:36
    DEXA-I trial will provide some. But
  498. 00:22:38
    yeah, DEXA-I really, yeah, it was,
  499. 00:22:41
    you
  500. 00:22:44
    know, it's gonna be much more, you
  501. 00:22:46
    know, high-quality data. So we'll look
  502. 00:22:49
    forward to that. Talk to us a little
  503. 00:22:51
    bit about anti-platelet reversal. Yeah,
  504. 00:22:55
    it's funny, it's platelets are sticky
  505. 00:22:58
    and I think that giving
  506. 00:22:59
    platelet-size-age patients is a sticky
  507. 00:23:01
    business because no one can seem to stop
  508. 00:23:04
    doing it. despite the patch trial,
  509. 00:23:06
    which took spontaneous ICH patients on
  510. 00:23:09
    various forms of anti-platelet therapy,
  511. 00:23:11
    like clopidogryl or aspirin, and we
  512. 00:23:14
    finally signed them to get platelet
  513. 00:23:16
    transfusions or not. And that study was
  514. 00:23:18
    stopped too, but not because the
  515. 00:23:20
    patients with getting platelets were
  516. 00:23:22
    doing better. In fact, they were dying
  517. 00:23:25
    at excess frequency. They were doing
  518. 00:23:27
    significantly worse. So what the
  519. 00:23:29
    guidelines tend to say now is, don't
  520. 00:23:32
    give platelets unless you're planning to
  521. 00:23:36
    take the patient to the OR for a ventric
  522. 00:23:39
    or craniotomy. And even in that setting,
  523. 00:23:39
    it's kind of belts and suspenders
  524. 00:23:39
    thinking, right? And maybe I get it,
  525. 00:23:40
    but you'll still see people giving
  526. 00:23:40
    platelet transfusions to a seven
  527. 00:23:40
    milliliter tholamic bleed, where you're
  528. 00:23:40
    just gonna treat medically in controlled
  529. 00:23:40
    blood pressure So it never, it not get
  530. 00:23:40
    even trick, right? So it, it,
  531. 00:24:05
    never made sense to me. Why would you
  532. 00:24:07
    do worse with a platelet transfusion? I
  533. 00:24:09
    think the best possible explanation that
  534. 00:24:12
    I've heard is that bags of blood
  535. 00:24:16
    products sitting on a shelf, those
  536. 00:24:18
    cellular elements can break down,
  537. 00:24:21
    release proteins that in effect act as
  538. 00:24:23
    cytokines. And so,
  539. 00:24:26
    yeah, you're giving these platelets,
  540. 00:24:27
    but you may also be sort of brewing the
  541. 00:24:30
    inflammatory systemic inflammatory
  542. 00:24:33
    response syndrome, or something like
  543. 00:24:35
    that, creating some kind of, you know,
  544. 00:24:37
    or amping up the SIRS response, that we
  545. 00:24:39
    know occurs in response to ICH. In fact,
  546. 00:24:43
    when you do tags in ICH patients,
  547. 00:24:46
    spontaneous ICH, right, just straight
  548. 00:24:48
    up hypertension, the most common
  549. 00:24:50
    finding is they're hyperquagable, right?
  550. 00:24:53
    It makes sense. Your body's like, whoa,
  551. 00:24:54
    I'm bleeding in my brain. Let's gotta
  552. 00:24:57
    stop that, right? And so the whole
  553. 00:24:59
    pendulum shifts towards hyperquagability
  554. 00:25:02
    Maybe there's inflammatory response.
  555. 00:25:04
    that goes with that already, and then
  556. 00:25:06
    you're adding more exogenous and
  557. 00:25:08
    inflammatory mediators. So DDAVP, yes,
  558. 00:25:12
    platelets? No, for ICH
  559. 00:25:16
    patients on anti-platelet agents that
  560. 00:25:18
    are not going to the OR. Let's talk a
  561. 00:25:22
    little
  562. 00:25:24
    about DDAVP. Tell me your thoughts
  563. 00:25:25
    about DDAVP. Okay, I do want to circle
  564. 00:25:28
    back to eight emergency reversal though
  565. 00:25:33
    DDAVP, or Desrepressin, induces a
  566. 00:25:37
    point thing micro kilogram injection
  567. 00:25:39
    will induce a one-time expression of von
  568. 00:25:43
    Wilibrand factor on the surface of all
  569. 00:25:47
    your platelets. And it's really was
  570. 00:25:49
    validated in NCH
  571. 00:25:53
    renal disease patients who have
  572. 00:25:55
    platelets as function. It was shown,
  573. 00:25:57
    DDAVP was shown to improve platelet
  574. 00:26:00
    function There were never any studies
  575. 00:26:02
    looking at bleeding or anything like
  576. 00:26:03
    that. But everybody gives the DDAVP
  577. 00:26:06
    because it doesn't seem to have any side
  578. 00:26:09
    effects and you do want to kind of do
  579. 00:26:12
    everything you can do, right, to
  580. 00:26:14
    normalize a cane hemostasis. So that's
  581. 00:26:17
    that's the dose So the DDAVP literature,
  582. 00:26:21
    if you think the comparing FF4 factor
  583. 00:26:25
    PCC and index is patchwork, the Desmond
  584. 00:26:28
    Press and literature is very patchwork.
  585. 00:26:31
    Many of those patients even got playlets
  586. 00:26:33
    or even in those trials, even in those
  587. 00:26:34
    studies, got anticoagulation reversal,
  588. 00:26:37
    but similarly, at least our our
  589. 00:26:39
    practice, as you mentioned step on us
  590. 00:26:41
    is basically we're going to reverse
  591. 00:26:42
    we're going to reverse plates we're
  592. 00:26:43
    going to get fluids and and Desmond
  593. 00:26:45
    Preston
  594. 00:26:49
    Yeah, John, I don't even pretend to
  595. 00:26:52
    say that we give Desmond Preston because
  596. 00:26:55
    the, the comparative data on DDAVP is
  597. 00:26:57
    so good, I don't even pretend, I just
  598. 00:26:59
    say like why not it can't hurt
  599. 00:27:04
    Let's, if you don't mind, let's go
  600. 00:27:06
    back to emergency reversal on code ICH.
  601. 00:27:09
    Sure.
  602. 00:27:11
    So, you know, we're coming out with
  603. 00:27:14
    coming out swinging with two
  604. 00:27:15
    recommendations. We feel that the time
  605. 00:27:19
    is now for the stroke community and
  606. 00:27:22
    future guidelines as soon as possible to
  607. 00:27:25
    adopt
  608. 00:27:33
    time based quality metrics for two
  609. 00:27:33
    commonly performed interventions Right.
  610. 00:27:33
    One of them is if you're controlling
  611. 00:27:34
    blood pressure initiate at least within
  612. 00:27:37
    60 minutes of door time. And if you're
  613. 00:27:40
    going to reverse. In a coagulation
  614. 00:27:45
    right from a VCA agent or an antenna
  615. 00:27:48
    agent. You should write the goal should
  616. 00:27:51
    be to initiate the administration that
  617. 00:27:55
    agent within 60 minutes Of door time.
  618. 00:27:59
    And you know, this is fun to talk about
  619. 00:28:01
    because there was a lot of back and.
  620. 00:28:04
    going back to the NCS session we did
  621. 00:28:07
    last fall and you know some voices were
  622. 00:28:10
    like 60 minutes too hard man come on
  623. 00:28:13
    take it easy I mean you know 90 minutes
  624. 00:28:16
    you know what about two hours there are
  625. 00:28:19
    arguments like you know takes time to
  626. 00:28:21
    mix up some of these agents the farming
  627. 00:28:23
    the time we use for pharmacy you know
  628. 00:28:25
    particularly in decks it was raised as
  629. 00:28:26
    an issue not it's easy to mix up and get
  630. 00:28:30
    ready to minister let's say as k-centra
  631. 00:28:32
    product for factor PCC but at the end of
  632. 00:28:35
    the day we felt you know what if we can
  633. 00:28:37
    do it for TPA it's 45 minutes for TPA
  634. 00:28:40
    right
  635. 00:28:42
    let's go game on right let's let's set
  636. 00:28:46
    the bar high and if it's hard let's work
  637. 00:28:51
    on ways to do better and make it easier
  638. 00:28:55
    and that's what we want to do a code ICH
  639. 00:28:57
    so we view code ICH as an enduring
  640. 00:29:01
    platform It's a concept we can rally
  641. 00:29:04
    around, and as further data accumulates
  642. 00:29:08
    and becomes available, the code ICH
  643. 00:29:11
    platform, it's really just jargin' for
  644. 00:29:14
    what you do in the first hour or two of
  645. 00:29:16
    an ICH, right? It's, you could,
  646. 00:29:18
    right, but we wanna rally around
  647. 00:29:24
    it and we wanna advocate for ICH care
  648. 00:29:26
    and ICH patient to get some of the
  649. 00:29:28
    spotlight and some of the limelight that
  650. 00:29:31
    that AIS enjoys in abundance. And ICH
  651. 00:29:38
    is like the little red-headed stepchild
  652. 00:29:40
    of stroke standing there in the darkness
  653. 00:29:42
    of the corner. And we wanna bring it
  654. 00:29:44
    out.
  655. 00:29:46
    Yeah, because as neurointensivists,
  656. 00:29:48
    and I think as neurointensivists, we
  657. 00:29:51
    often are the first, we are among the
  658. 00:29:53
    first call for these patients. We've
  659. 00:29:55
    also managed these patients on the back
  660. 00:29:57
    end. So similar to what you're saying,
  661. 00:29:59
    behooves us to pay close attention to
  662. 00:30:02
    how we manage these patients hyper
  663. 00:30:03
    acutely upfront because we'll be taking
  664. 00:30:05
    care of them on the back end. Yeah,
  665. 00:30:07
    and I want to address something else
  666. 00:30:09
    that we realized.
  667. 00:30:11
    Acute ischemic stroke, stroke services,
  668. 00:30:15
    stroke departments or divisions. A lot
  669. 00:30:19
    of them are really focused on AIS and do
  670. 00:30:22
    a fantastic job and a big piece of that
  671. 00:30:25
    are all the quality metrics that you
  672. 00:30:26
    generate every month, together with the
  673. 00:30:28
    guidelines and stroke indicators. I see
  674. 00:30:31
    it just a little bit more orphan like
  675. 00:30:34
    neurotensivist but it is a form of
  676. 00:30:36
    stroke. The stroke program, you got
  677. 00:30:38
    neurosurgery and I really personally, I
  678. 00:30:41
    think the neurocritical care crowd is
  679. 00:30:43
    kind of firmly in with the ICH. I think
  680. 00:30:47
    we could do better job getting the
  681. 00:30:50
    stroke divisions. Embracing ICH, just
  682. 00:30:55
    giving it just as much of a big, warm
  683. 00:30:58
    hug. as they do for acute ischemic
  684. 00:31:00
    stroke. I think there's a little bit of
  685. 00:31:02
    like, that's neurosurgery,
  686. 00:31:05
    neurocritical, you know? But it's
  687. 00:31:07
    really, you know, let's be honest, in
  688. 00:31:10
    our hospitals, there's no
  689. 00:31:13
    infrastructure to measure quality. It's
  690. 00:31:16
    already there in spades. And it exists,
  691. 00:31:19
    you know, with your stroke center
  692. 00:31:20
    director and your stroke coordinator.
  693. 00:31:22
    So they should be really interested in
  694. 00:31:26
    improving care and outcomes for ICH.
  695. 00:31:29
    Well said. All right, well, thank you
  696. 00:31:32
    all for listening. I hope you, you
  697. 00:31:35
    hope you enjoyed the talk. And thank
  698. 00:31:37
    you so much to Dr. Praneer.