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Episode 113: PERSPECTIVES - Dr Daniel Hanley

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Episode 111: PERSPECTIVES - Dr Daniel Hanley

Contributors

  • Daniel Hanley, MD

    Since 1996, Dr. Hanley has been a Professor of Neurology, Neurosurgery and Anesthesia/Critical Medicine at Johns Hopkins Medical Institutions. Since 1999, Dr. Hanley has also been Professor, School of Nursing, the Jeffrey and Harriett Legum Professor of Acute Care Neurology and Director of Brain Injury Outcomes Program at Johns Hopkins Medical Institutions. Dr. Hanley is a graduate of Williams College and Cornell University Medical College and has board certification in internal medicine, neurology and psychiatry. Dr. Hanley is a leading expert on multiple types of brain injury and has received more than 40 clinical and basic research grants, predominately from the National Institute of Health and the FDA Orphan drugs program. He has published more than 190 articles in peer-reviewed journals, has received the Alexander Humboldt Research Prize for his accomplishments in brain injury research and has extensive clinical trials experience in that field. His trainees are directors of over 20 brain intensive care units across the United States. Dr. Hanley is on the board of directors of the National Stroke Association and has developed nationally recognized education and training programs for that organization. He has significant experience in the areas of clinical trials design, organization and interpretation: drug development: device development and regulatory compliance. He is the principle investigator for the NIH sponsored MISTIE and CLEAR trials investigating minimally invasive neurosurgical techniques to treat hemorrhagic stroke.

  • Nicholas A. Morris, MD

    Assistant Professor and Fellowship Director
    Division of Neurocritical Care and Emergency Neurology
    Department of Neurology
    University of Maryland School of Medicine Medicine

  1. 00:00:19
    Okay, Hi, everyone, I'm your host,
  2. 00:00:22
    Nicholas Marsh, University Of Maryland,
  3. 00:00:23
    Shock Trauma Hospital, and this is the
  4. 00:00:25
    Neuro Critical Care Society Podcast
  5. 00:00:27
    today, as part of our perspective
  6. 00:00:29
    series, We have the absolute honor of
  7. 00:00:31
    having Dr. Daniel Hanley and from Johns
  8. 00:00:34
    Hopkins University. Dr. Hanley is a
  9. 00:00:36
    graduate of Williams College and Cornell
  10. 00:00:38
    University Medical College. He's been a
  11. 00:00:40
    professor of neurology neurosurgery in
  12. 00:00:42
    anesthesiology, critical care medicine
  13. 00:00:45
    at the Johns Hopkins University School
  14. 00:00:46
    of Medicine, since nineteen ninety six,
  15. 00:00:48
    He has over three hundred articles in
  16. 00:00:51
    peer -reviewed journals. He has
  17. 00:00:53
    received the Alexander Xander Humboldt
  18. 00:00:54
    Research Prize for his accomplishments
  19. 00:00:56
    in brain injury research and has
  20. 00:00:58
    extensive clinical trial experience in
  21. 00:01:00
    the fields of stroke hemorrhage, trauma
  22. 00:01:01
    and brain infections are most recently,
  23. 00:01:04
    he's really focus and interest cerebral
  24. 00:01:05
    hemorrhage, and hopefully we'll talk
  25. 00:01:06
    about some of those pivotal studies.
  26. 00:01:08
    Later in our discussion. Now he was the
  27. 00:01:10
    principal investigator for the Nh
  28. 00:01:12
    Sponsored, Misty three and clear three
  29. 00:01:13
    trials investigating minimally invasive
  30. 00:01:15
    neurosurgical techniques to treat
  31. 00:01:17
    hemorrhagic stroke. Am Dr. Hanley it's
  32. 00:01:19
    a real honor to have you on the podcast,
  33. 00:01:21
    and thanks for joining us. Oh, Nick,
  34. 00:01:24
    it's wonderful to be here and it's nice
  35. 00:01:28
    to do as an old person who have have got
  36. 00:01:34
    to talk about the about the past. Yeah,
  37. 00:01:38
    Well, we're here that we're here to
  38. 00:01:40
    hear the stories, cause, I don't think
  39. 00:01:41
    these stories have been told enough, so
  40. 00:01:43
    why don't you take us back and let's
  41. 00:01:46
    learn a little bit about the history of
  42. 00:01:48
    of neuro critical care through your
  43. 00:01:49
    experience at Hopkins, which I, I
  44. 00:01:51
    think as as Ellen Roper said previously
  45. 00:01:53
    on this podcast might be the very first
  46. 00:01:55
    narrow. I see you in the United States.
  47. 00:01:57
    Right,
  48. 00:02:00
    Well, sure we can, we can talk about
  49. 00:02:03
    the about that and a couple of things.
  50. 00:02:10
    In the introduction. You forgot that I
  51. 00:02:14
    may Brunswick high school, Brunswick,
  52. 00:02:17
    Maine. dragon from a small town public
  53. 00:02:22
    high school, and there's no reason for
  54. 00:02:26
    you to know, but I went to medical
  55. 00:02:28
    school with Alan Roper, and he was my
  56. 00:02:33
    superior. He was a class ahead of me,
  57. 00:02:38
    and I think two or three years
  58. 00:02:44
    ahead in training and becoming a faculty
  59. 00:02:47
    member
  60. 00:02:50
    Because he did, I think, two years of
  61. 00:02:54
    medicine and then moved into
  62. 00:03:00
    neurology, and I spent three years in
  63. 00:03:03
    medicine and then a neurology fellowship
  64. 00:03:07
    before I ever did my neurology residency
  65. 00:03:10
    So I was a little retarded compared
  66. 00:03:12
    toand to
  67. 00:03:14
    set the.
  68. 00:03:17
    The story straight, and I actually
  69. 00:03:21
    Allen had the first running Neurology
  70. 00:03:26
    department unit and I actually went to
  71. 00:03:33
    his training course the year I started
  72. 00:03:36
    of the neuro critical care unit and so I,
  73. 00:03:42
    I would personally give him credit okay,
  74. 00:03:46
    but he's giving you credit, so it seems
  75. 00:03:48
    like a credit credit all around, So
  76. 00:03:50
    what what was happening and and Hopkins
  77. 00:03:53
    at the time where you decided this is
  78. 00:03:56
    something that needed to be done, or
  79. 00:03:57
    there was sort of a gap to fill your? I
  80. 00:04:01
    didn't really decide I had an interest
  81. 00:04:05
    in this area, because
  82. 00:04:10
    as Cornell Medical college.
  83. 00:04:17
    Students above Alan and I grew up in an
  84. 00:04:22
    environment that had a very good cardiac
  85. 00:04:27
    critical care, and there there had been
  86. 00:04:30
    some leadership roles, and in that area
  87. 00:04:34
    in the sixties and
  88. 00:04:37
    seventies and and a good medical,
  89. 00:04:42
    infectious disease, pulmonary and
  90. 00:04:47
    critical care capabilities that
  91. 00:04:49
    eventually morphed into that part of the
  92. 00:04:56
    critical care medicine society,
  93. 00:05:03
    so we were exposed to a lot of evolving
  94. 00:05:07
    general. I see you care,
  95. 00:05:12
    and being an internist, I had
  96. 00:05:15
    capabilities in that area. And there
  97. 00:05:18
    were no
  98. 00:05:20
    credentialing of icy you physicians, at
  99. 00:05:23
    the time
  100. 00:05:25
    I did my neurology training at the Johns
  101. 00:05:28
    Hopkins and Johns Hopkins out, and a
  102. 00:05:34
    long interest in the ill neurologic
  103. 00:05:39
    neurosurgical patients Harvey Cushing,
  104. 00:05:43
    when he finished his residency at
  105. 00:05:45
    Hopkins did what both surgically and
  106. 00:05:51
    medically trained
  107. 00:05:55
    newly minted specialists dead at that
  108. 00:06:00
    time, In the late eighteenth, Eighteen
  109. 00:06:03
    hundreds, early Nineteenth century. He
  110. 00:06:06
    went to Europe, and saw what was going
  111. 00:06:09
    on in Britain, but particularly in in
  112. 00:06:14
    France and Germany, which were.
  113. 00:06:17
    Probably ahead of Britain at that time,
  114. 00:06:20
    and medicine, and he took the
  115. 00:06:25
    the sphygmomanometer, the blood
  116. 00:06:28
    pressure cuff, which was being used in
  117. 00:06:32
    a in general medicine, but also in the
  118. 00:06:34
    A in the operating theatre, and he
  119. 00:06:37
    brought it back to to Johns Hopkins,
  120. 00:06:41
    and he thought it would be good to know
  121. 00:06:43
    what the blood pressure was of patients
  122. 00:06:45
    he was operating on a little later at at
  123. 00:06:49
    At At Hopkins, Walter Dandy, of Who
  124. 00:06:55
    Cushing train, but had a rivalry with
  125. 00:06:59
    and developed some of the of the
  126. 00:07:03
    invasive ventricular procedures,
  127. 00:07:05
    including ventricular, last me, and
  128. 00:07:07
    ventricular puncture which we we now use
  129. 00:07:10
    in the Neuro critical care unit and
  130. 00:07:12
    another parts of neurosurgery.
  131. 00:07:17
    and he developed the idea that
  132. 00:07:20
    neurosurgical patients after an
  133. 00:07:22
    operation should be observed in a
  134. 00:07:26
    specialized unit. And I think Tom Black
  135. 00:07:28
    has talked a little bit about that. So
  136. 00:07:32
    there was a history of saying that
  137. 00:07:37
    patients with neurologic diseases needed
  138. 00:07:41
    specialty care for their whole body
  139. 00:07:43
    systems that had existed at Hopkins.
  140. 00:07:49
    Don Long was the chief of neurosurgery
  141. 00:07:52
    at the time that I started the unit.
  142. 00:07:56
    And it was not me but others. My, the
  143. 00:08:01
    leaders of the institution that said
  144. 00:08:04
    intensive care medicine is evolving as a
  145. 00:08:08
    specialty Access to surgical intensive
  146. 00:08:13
    care was very limited for Dr. Long. He
  147. 00:08:18
    was allowed to have either one or two
  148. 00:08:20
    patients, but no more in the surgical
  149. 00:08:24
    intensive care unit. And access for Guy
  150. 00:08:30
    McCann and his vice chair, Chip Moses,
  151. 00:08:38
    was non-existent for neurologic
  152. 00:08:43
    critically ill patients You had to call
  153. 00:08:46
    a consult from the Medical Intensive
  154. 00:08:49
    Care Unit, which was predominantly a
  155. 00:08:52
    pulmonary unit in order to assess
  156. 00:08:57
    whether or not your patient required
  157. 00:09:00
    ventilation. And that wasn't a full
  158. 00:09:04
    assessment of critical care needs
  159. 00:09:08
    They were joined by a pediatric
  160. 00:09:14
    cardiologist, Mark Rogers, who Was the
  161. 00:09:17
    chairman of anesthesia so he was triple
  162. 00:09:20
    boarded in pediatrics cardiology and
  163. 00:09:24
    anesthesia and he wanted he was younger
  164. 00:09:28
    than either Mccann or Don Long, and he,
  165. 00:09:33
    he wanted to evolve the anesthesia
  166. 00:09:36
    department into an Anesthesia critical
  167. 00:09:39
    care medicine department, so, and it
  168. 00:09:43
    served his needs from a departmental
  169. 00:09:47
    strategy perspective to make that
  170. 00:09:49
    alliance
  171. 00:09:52
    without alliance, and after a decade of
  172. 00:09:57
    trying to get a neuro critical care unit,
  173. 00:10:00
    Don long was successful, and he hired
  174. 00:10:05
    or the year before we started at a a
  175. 00:10:09
    former
  176. 00:10:12
    nurse educator from your institution.
  177. 00:10:16
    from shock trauma, Judith Ski-Lauer,
  178. 00:10:19
    who was the head of
  179. 00:10:24
    a trauma and neurosurgery ICU
  180. 00:10:32
    at Washington Hospital Center
  181. 00:10:37
    to focus solely on neural. And she and
  182. 00:10:43
    I and an anesthesiologist from who was a
  183. 00:10:50
    newly minted trainee from Mark Rogers
  184. 00:10:53
    Department Cecil Burrell started the
  185. 00:10:57
    Hopkins unit to address that need. And
  186. 00:11:01
    we started it on a
  187. 00:11:08
    temporary or conditional basis that
  188. 00:11:13
    neither
  189. 00:11:16
    the surgical intensive care unit
  190. 00:11:19
    leadership and the Department of Surgery
  191. 00:11:22
    or the medical intensive care unit
  192. 00:11:24
    leadership and the
  193. 00:11:28
    Department of Medicine saw a true need
  194. 00:11:30
    for this. They objected to taking care
  195. 00:11:36
    of our own patients
  196. 00:11:41
    And the hospital in its wisdom said,
  197. 00:11:45
    Well, maybe it'll work, maybe it won't,
  198. 00:11:47
    so we'll try it for a year and see what
  199. 00:11:52
    happens. So they temporarily assigned
  200. 00:11:56
    us four beds in the step-down area of
  201. 00:12:01
    the surgical intensive care unit,
  202. 00:12:05
    and that was the first unit.
  203. 00:12:09
    We had two rooms So. Oh.
  204. 00:12:13
    Oh.
  205. 00:12:17
    Judith or ski lower, which is how she
  206. 00:12:19
    liked to be called,
  207. 00:12:23
    knew that in all ICUs, visual
  208. 00:12:26
    observation is critical. And I think as
  209. 00:12:30
    the neuro story evolves, it's even more
  210. 00:12:34
    critical in the neuropatient because one
  211. 00:12:36
    of the top skills is actual visual
  212. 00:12:39
    observation patient. So we took down
  213. 00:12:42
    the wall between the two rooms and just
  214. 00:12:45
    left
  215. 00:12:47
    the toilet area. So you had to cram
  216. 00:12:53
    usually three nurses,
  217. 00:12:57
    a couple of doctors, an attending
  218. 00:13:00
    physician, and then all the visiting
  219. 00:13:02
    services, probably in a 70-square-foot
  220. 00:13:08
    area. And we thought that was pretty
  221. 00:13:12
    hard because you're constantly. moving
  222. 00:13:17
    around someone else and trying not to
  223. 00:13:22
    push or
  224. 00:13:25
    treat them rudely,
  225. 00:13:29
    but it had the advantage that you could
  226. 00:13:32
    see all four patients at once, and that
  227. 00:13:36
    turned out to be a very helpful
  228. 00:13:39
    advantage. So that's how we started,
  229. 00:13:42
    and that's the beginning of my
  230. 00:13:47
    40-year-to-life sentence as a attending
  231. 00:13:50
    physician at Johns Hopkins. That's
  232. 00:13:53
    great. I'm sure there were some growing
  233. 00:13:56
    pains over the years. What were some of
  234. 00:13:57
    the major hurdles that you faced in
  235. 00:14:01
    developing things over maybe that first
  236. 00:14:04
    five to ten-year period? Sure. Well,
  237. 00:14:08
    the biggest hurdle, I think, was
  238. 00:14:13
    there was no textbook It was no plan of
  239. 00:14:17
    there was a not much strategy other than
  240. 00:14:21
    I do in neurology and neurosurgery
  241. 00:14:26
    patients were increasingly recognised as
  242. 00:14:32
    a severely ill at some stages in their
  243. 00:14:35
    illness and needing of I you support,
  244. 00:14:39
    and needing to have their icy, you
  245. 00:14:43
    support integrated into
  246. 00:14:47
    their care at
  247. 00:14:51
    a whole body level, as opposed to the
  248. 00:14:55
    the prior model of well. This is a
  249. 00:14:58
    polio patient. They can't breathe, but
  250. 00:15:01
    all we have to do is put them on a
  251. 00:15:06
    ventilator or or use of an iron lung
  252. 00:15:12
    with a negative pressure. Ventilation
  253. 00:15:17
    to meet their need, and the you know,
  254. 00:15:20
    we'll see if they survive, then we'll
  255. 00:15:23
    see what they look like
  256. 00:15:26
    and and that thought process I think was
  257. 00:15:29
    was not wrong. I think it was pragmatic
  258. 00:15:33
    because there were very few primary
  259. 00:15:37
    disease specific interventions for
  260. 00:15:40
    neurologic diseases, and if you don't
  261. 00:15:43
    mind, maybe for some of our listeners
  262. 00:15:45
    who don't serve now some of the history
  263. 00:15:47
    of one of our primary diseases, and
  264. 00:15:51
    could you could you discuss how subdural
  265. 00:15:53
    haemorrhage was managed and in those
  266. 00:15:55
    early days, and and how that's evolved,
  267. 00:15:59
    Sure that sounds upset. I mean someone.
  268. 00:16:03
    It's a similar story to polio and yell.
  269. 00:16:07
    I think early on and off the supper at
  270. 00:16:12
    nor hemorrhage.
  271. 00:16:15
    I was.
  272. 00:16:21
    Partially recognizable, because in the
  273. 00:16:24
    pre-CT era, you didn't have an easy
  274. 00:16:28
    test for blood in the brain that was
  275. 00:16:32
    non-invasive, and not everybody with
  276. 00:16:37
    syncope or severe headache or some
  277. 00:16:39
    combination of those got a lumbar
  278. 00:16:41
    puncture And then they did,
  279. 00:16:45
    if they were.
  280. 00:16:53
    comatose or stuporous, they often were
  281. 00:16:58
    just placed in a hospital bed and
  282. 00:17:04
    cared for with intravenous fluids
  283. 00:17:11
    and occasional blood pressure
  284. 00:17:13
    assessments with a sphigmomanometer
  285. 00:17:18
    and maybe some wall oxygen if that was
  286. 00:17:21
    thought to be needed. But they had to
  287. 00:17:25
    awaken before most people would become
  288. 00:17:29
    interested
  289. 00:17:31
    in evaluating them. And there were
  290. 00:17:34
    people who were poorly responsive who
  291. 00:17:39
    didn't get diagnosed because there
  292. 00:17:41
    wasn't a universal way to look for blood
  293. 00:17:45
    in the brain.
  294. 00:17:47
    There was data I'm. starting in the 50s
  295. 00:17:53
    and 60s that with impaired consciousness
  296. 00:17:56
    or a so-called high-grade subarachnoid
  297. 00:17:59
    hemorrhage
  298. 00:18:02
    that the outcomes were poor and surgery
  299. 00:18:05
    was dangerous. So the controversy of
  300. 00:18:08
    the time was, do you do aggressive
  301. 00:18:11
    diagnosis and do you do early surgery?
  302. 00:18:15
    And it really was only
  303. 00:18:19
    in the late 70s and into the mid 80s
  304. 00:18:23
    that
  305. 00:18:26
    more aggressive diagnosis oriented and
  306. 00:18:31
    treatment oriented neurosurgeons began
  307. 00:18:34
    to say, you know, hey, it's the same
  308. 00:18:37
    problem as a mild of
  309. 00:18:44
    grade one subarachnoid hemorrhage or an
  310. 00:18:48
    asymptomatic aneurysm, you're not going
  311. 00:18:50
    to
  312. 00:18:52
    fix the problem and decrease the risk
  313. 00:18:54
    until you treat the lesion and gradually
  314. 00:19:00
    it evolved that these people should be
  315. 00:19:02
    in an ICU, that we should do an early
  316. 00:19:07
    angiogram and that they might need
  317. 00:19:13
    treatment for hydrocephalus and
  318. 00:19:17
    that they might require
  319. 00:19:21
    much stricter blood pressure management
  320. 00:19:23
    and all the things in nutrition and
  321. 00:19:27
    airway protection that we now do.
  322. 00:19:30
    Yeah, it's really changed so
  323. 00:19:32
    dramatically from those early days and I
  324. 00:19:34
    think it always amazes me how far we've
  325. 00:19:39
    come and I guess Hopkins is a good
  326. 00:19:42
    example where you've really the tools
  327. 00:19:44
    that were used in the initial management,
  328. 00:19:46
    the blood pressure cuff. External
  329. 00:19:48
    ventricular drain in many ways are tied
  330. 00:19:51
    to your institution's right. It's true,
  331. 00:19:54
    and I think that story exists for all
  332. 00:19:57
    the diseases that. Oh that we now treat,
  333. 00:20:01
    give me a a one minute pause while you
  334. 00:20:04
    sure.
  335. 00:20:14
    All right, so I interrupted you when
  336. 00:20:17
    you were talking about some of the large
  337. 00:20:18
    hurdles in the early days, but one
  338. 00:20:21
    thing you had mentioned was there was no
  339. 00:20:22
    textbook on how to manage these patients.
  340. 00:20:25
    So how did you come to a consensus about
  341. 00:20:27
    what to do?
  342. 00:20:30
    I think we use the usual methods of
  343. 00:20:36
    medicine and medical inquiry and medical
  344. 00:20:40
    training And
  345. 00:20:44
    I have stayed in the area of
  346. 00:20:48
    neurocritical care for my entire career
  347. 00:20:52
    because there were so many things that
  348. 00:20:54
    needed to be done and that there are so
  349. 00:20:57
    many interesting problems.
  350. 00:21:00
    I identified
  351. 00:21:03
    early on that we needed organized
  352. 00:21:07
    research and development And I think
  353. 00:21:10
    there were.
  354. 00:21:13
    Women manpower perspective,
  355. 00:21:17
    and maybe five or six questions.
  356. 00:21:22
    You know, The first was what we were
  357. 00:21:24
    talking about what to do with the
  358. 00:21:28
    critically ill neurologic patient as
  359. 00:21:31
    critical care, or I see you care
  360. 00:21:33
    evolved from cardiopulmonary care and
  361. 00:21:36
    surgical trauma care, and the second
  362. 00:21:39
    was coo is a legitimate patient, or
  363. 00:21:43
    what diseases, and which specialties
  364. 00:21:47
    patients were appropriate for a narrow,
  365. 00:21:51
    I see you, and the third was what
  366. 00:21:56
    skills are mission critical,
  367. 00:21:59
    and
  368. 00:22:01
    I'd list
  369. 00:22:04
    a shortened and neurological assessment
  370. 00:22:08
    of airway skills, ventilation, skills,
  371. 00:22:11
    blood pressure support.
  372. 00:22:14
    arrhythmia, diagnosis and management,
  373. 00:22:18
    nutritional support, understanding of
  374. 00:22:22
    coagulation and bleeding interventions,
  375. 00:22:27
    and then
  376. 00:22:29
    an understanding of wherever the
  377. 00:22:33
    evolving front was in all the neuro
  378. 00:22:37
    disease specific interventions. And the
  379. 00:22:41
    key ones were where nothing was
  380. 00:22:45
    available, but was evolving
  381. 00:22:48
    cerebrovascular
  382. 00:22:50
    infection and inflammatory diseases,
  383. 00:22:52
    which includes the nerve and muscle
  384. 00:22:56
    diseases, status epilepticus, those
  385. 00:22:59
    would be some of the big areas where
  386. 00:23:03
    there needed to be skills.
  387. 00:23:06
    The next problem was how to share
  388. 00:23:10
    information about a new specialty, was
  389. 00:23:13
    really your question, and then perhaps
  390. 00:23:17
    the final one was how to train others.
  391. 00:23:22
    My personal assessment of those five
  392. 00:23:28
    areas that Johns Hopkins was that
  393. 00:23:34
    if we were going to survive as a
  394. 00:23:36
    specialty, we needed something to teach
  395. 00:23:42
    other than general medical and surgical
  396. 00:23:45
    skills. We needed those skills, but we
  397. 00:23:50
    didn't have a lot to teach, so that
  398. 00:23:53
    there was a role for basic lab research,
  399. 00:23:58
    and I took the fellowship training that
  400. 00:24:03
    I had had between medicine and neurology,
  401. 00:24:08
    and a called what's did I, neurology
  402. 00:24:08
    after, then
  403. 00:24:14
    systems, physiology, fellowship,
  404. 00:24:18
    working in
  405. 00:24:23
    a ventilation and circulatory control
  406. 00:24:25
    lab that was run by a physiologist,
  407. 00:24:28
    Richard Traitzman, and
  408. 00:24:31
    we did molecular physiology on holy
  409. 00:24:35
    animal systems.
  410. 00:24:37
    And I was fortunate enough to
  411. 00:24:44
    working with Dr. Traitzman and
  412. 00:24:47
    a man named David Wilson, who was
  413. 00:24:50
    another physiologist and a man named
  414. 00:24:53
    Raymond Kohler, who is now head of the
  415. 00:24:56
    program Traitzman
  416. 00:24:59
    started, to have a physiologist as both
  417. 00:25:04
    teachers and colleagues, and that
  418. 00:25:07
    matched well to ICU skills. So and
  419. 00:25:14
    Through their help, we had a series of
  420. 00:25:20
    multiple and I edge grants over a twenty
  421. 00:25:23
    year period, and we started to doing a
  422. 00:25:29
    two year fellowship with one year of
  423. 00:25:31
    clinical exposure and one year of lab
  424. 00:25:33
    exposure totaled, but both intertwined
  425. 00:25:37
    over a two year period and and I think
  426. 00:25:40
    that became critical
  427. 00:25:43
    to the legitimacy of Of of the the
  428. 00:25:48
    specialty, because we both expose
  429. 00:25:53
    people to the problems that existed and
  430. 00:25:56
    solutions of the time, but gave them a
  431. 00:25:58
    background in physiology and
  432. 00:26:03
    in both humans, in the I C U, and an
  433. 00:26:07
    animal physiology, diving deeper into
  434. 00:26:09
    the mechanisms of regulation and. The
  435. 00:26:14
    serve of our trainees well, I was lucky
  436. 00:26:20
    enough to get a a very nice, a
  437. 00:26:24
    scientific training. Start a grant from
  438. 00:26:27
    the Charles Dana Foundation and have
  439. 00:26:32
    twenty years of the support from them,
  440. 00:26:36
    which allowed for the trainees to to
  441. 00:26:41
    have lab time and then have
  442. 00:26:46
    their work more than anything else. I
  443. 00:26:50
    set up some of the answers to the the
  444. 00:26:53
    five questions I post on it its entire
  445. 00:26:57
    stake, and in Kent, can we take one
  446. 00:26:59
    step back, though, and you mentioned
  447. 00:27:02
    that initially then your ice, he was
  448. 00:27:05
    sort of a conditional. I see you, and
  449. 00:27:06
    there is some resistance from our
  450. 00:27:08
    colleagues in the surgery, surgery went
  451. 00:27:10
    realm, and I'll from critical care.
  452. 00:27:13
    And and you spoke to some of these
  453. 00:27:14
    things that he said offered some
  454. 00:27:16
    legitimacy to what we were doing, So
  455. 00:27:18
    what what was happening at Hopkins that
  456. 00:27:21
    really established the ice you as
  457. 00:27:22
    something that was going to stick around
  458. 00:27:24
    and give you the opportunity to train
  459. 00:27:26
    all these people who had been gotten
  460. 00:27:28
    sort of proselytize and spread neuro
  461. 00:27:30
    critical care Throughout How how did
  462. 00:27:32
    that really gain a foothold? They'll
  463. 00:27:36
    all well,
  464. 00:27:39
    You know you would think there should be
  465. 00:27:42
    a given you know the five things that I
  466. 00:27:44
    described that we needed to evolve a
  467. 00:27:46
    specialty that you could come up with a
  468. 00:27:49
    list of milestones that you might mean,
  469. 00:27:55
    but I think it it didn't work quite that
  470. 00:27:58
    way. We didn't kill. Anybody could
  471. 00:28:02
    start a fight. That's always a good
  472. 00:28:05
    start and we met a need that was a
  473. 00:28:08
    bigger need outside of neuro critical
  474. 00:28:11
    care. Which was to support and evolve
  475. 00:28:16
    to departments, neurosurgery and
  476. 00:28:18
    neurology, and a and a third partner
  477. 00:28:21
    department anesthesia, which had the
  478. 00:28:25
    same training mission, so we helped
  479. 00:28:28
    them better do their mission, and when
  480. 00:28:34
    the individuals
  481. 00:28:37
    who oversee the yearly allocation of
  482. 00:28:40
    resources saw that those departments
  483. 00:28:44
    were robust and beating their overall
  484. 00:28:46
    needs, and we were moved out of the
  485. 00:28:51
    four bed unit and they allocated money
  486. 00:28:55
    to
  487. 00:28:57
    build a on a real eight bed unit around
  488. 00:29:02
    a patient needs, and that included a
  489. 00:29:08
    glass, but walled off areas so that.
  490. 00:29:11
    individual patients could have a more
  491. 00:29:15
    quieter controlled environment which we
  492. 00:29:18
    didn't do well at in the 80s but they've
  493. 00:29:22
    eventually gotten there.
  494. 00:29:26
    And we had that as a home for about six
  495. 00:29:32
    or seven years and as the realization
  496. 00:29:38
    came across Thank you.
  497. 00:29:44
    specialist, neurologist, and
  498. 00:29:47
    neurosurgeons working in smaller
  499. 00:29:49
    communities that didn't have this
  500. 00:29:51
    resource that for a small percentage of
  501. 00:29:53
    their patients this resource was helpful.
  502. 00:29:57
    Then we started getting referrals and we
  503. 00:30:02
    ended up with a 12-bed unit and another
  504. 00:30:08
    four or five step-down beds Yeah, if
  505. 00:30:12
    you build it, they will come, I guess,
  506. 00:30:14
    if there's. Right.
  507. 00:30:20
    The worst expectations of the naysayers
  508. 00:30:24
    are not realized. I
  509. 00:30:31
    was a trained neurologist who also was a
  510. 00:30:35
    boarded internist Cecil Burrell was a
  511. 00:30:38
    trained anesthesiologist who was a
  512. 00:30:40
    boarded internist. And had done a year
  513. 00:30:43
    of a general shock trauma fellowship,
  514. 00:30:47
    So between the two of us, we had
  515. 00:30:52
    some degree of the coral. What have
  516. 00:30:54
    become the core competencies of the The
  517. 00:30:57
    specialty, and could begin to to share
  518. 00:31:01
    that with others and I am certain that,
  519. 00:31:05
    but there are things in our practice
  520. 00:31:08
    that we could have done better, so you
  521. 00:31:11
    know that's the opposite of while we
  522. 00:31:13
    didn't kill anybody, not not obviously,
  523. 00:31:17
    but you know we did a good enough job,
  524. 00:31:21
    so that
  525. 00:31:23
    one of the consumers of healthcare at
  526. 00:31:26
    Hopkins is faculty and family, and and
  527. 00:31:29
    they come from all departments, and
  528. 00:31:32
    they were happy with our care and Sky
  529. 00:31:36
    lauer and seeing day in day out trauma
  530. 00:31:41
    care. At the University of Maryland and
  531. 00:31:45
    have
  532. 00:31:48
    at Washington hospital center knew how
  533. 00:31:51
    important it was to be a family centric,
  534. 00:31:56
    and to meet the
  535. 00:31:59
    intellectual or emotional or both needs
  536. 00:32:03
    of the family of the patients you had,
  537. 00:32:07
    so we were perhaps a little more family
  538. 00:32:11
    friendly than some of the other icy use,
  539. 00:32:14
    and I think that helped an acceptance as
  540. 00:32:16
    well and that that's really interesting.
  541. 00:32:19
    Think it seems that in only recently I
  542. 00:32:23
    think Er, we are really embracing the
  543. 00:32:25
    role of the family and critical illness
  544. 00:32:27
    and family engagement, and I in
  545. 00:32:30
    recovery trajectories and, and but
  546. 00:32:33
    that's that's very interesting that as
  547. 00:32:35
    De Lauer recognize that back back then
  548. 00:32:38
    and that navy made a large difference in
  549. 00:32:40
    the eighties, Yeah? Yeah, and so you
  550. 00:32:44
    mentioned kind of some of the goals you
  551. 00:32:48
    set out, which if I summarize, right,
  552. 00:32:51
    one was sort of to define what is
  553. 00:32:55
    neurocritical care? What are the
  554. 00:32:56
    illnesses that we should be taking care
  555. 00:32:58
    of and who are the people that do it and
  556. 00:33:00
    what are the competencies? Two is
  557. 00:33:03
    kind of how do we gather and share data?
  558. 00:33:05
    And three is a little bit like how do we
  559. 00:33:07
    train others to continue this? Take me
  560. 00:33:13
    through, what are some of the
  561. 00:33:14
    achievements that you're really proud of
  562. 00:33:15
    either of your own or that your trainees
  563. 00:33:17
    that, as you said, have gone on to
  564. 00:33:18
    answer many of these questions? What
  565. 00:33:21
    are the things looking back that you
  566. 00:33:22
    think have made the largest
  567. 00:33:23
    contributions?
  568. 00:33:26
    Sure.
  569. 00:33:30
    Well,
  570. 00:33:34
    maybe the thing that I'm most proud of
  571. 00:33:38
    is that
  572. 00:33:40
    almost all of the
  573. 00:33:43
    trainees during my leadership time, and
  574. 00:33:47
    since then under
  575. 00:33:51
    Mark Mersky, Romer G. O'Kaden, and
  576. 00:33:55
    Jose Suarez,
  577. 00:33:57
    each of whom I had a part in their
  578. 00:33:59
    training, have stayed in neurocritical
  579. 00:34:02
    care and have committed to this mission
  580. 00:34:06
    and these four or five main main
  581. 00:34:10
    questions. I'm
  582. 00:34:15
    equally proud of
  583. 00:34:19
    trainees who aren't physicians, who
  584. 00:34:23
    have oriented themselves to the critical
  585. 00:34:28
    care model that it's a poly-professional
  586. 00:34:33
    And, you know, the story about
  587. 00:34:35
    Schilauer and families projects into you
  588. 00:34:43
    a
  589. 00:34:45
    PhD, Lourdes, Carho Apoma, who's
  590. 00:34:48
    studying family interactions and how can
  591. 00:34:52
    we provide families with better
  592. 00:34:55
    information so they make informed
  593. 00:34:59
    decisions in the ICU.
  594. 00:35:03
    Unfortunately, she's deceased, a woman
  595. 00:35:05
    named Rebecca Rubenoff, who
  596. 00:35:10
    devoted her academic life to the
  597. 00:35:12
    nutrition of neurocritical care patients.
  598. 00:35:17
    There have been
  599. 00:35:20
    several pharmacists who have become
  600. 00:35:25
    neurocritical care leaders. So I think
  601. 00:35:30
    the people who have carried on the
  602. 00:35:32
    interest is probably the
  603. 00:35:35
    single most important contribution that
  604. 00:35:42
    Dr. Burrell and Skylauer and myself
  605. 00:35:44
    with the support of Don Long, Guy
  606. 00:35:47
    McCann, Chip Moses, and the hospital
  607. 00:35:52
    catalyzed.
  608. 00:35:56
    Was there a particular case that sticks
  609. 00:36:01
    with you when you think back over all
  610. 00:36:03
    the years that I think we probably all
  611. 00:36:06
    have certain cases that we really
  612. 00:36:08
    remember or we really get involved with?
  613. 00:36:10
    Is there one that really is at the
  614. 00:36:13
    forefront of your mind when you look
  615. 00:36:14
    back at your career?
  616. 00:36:22
    Yeah, names will be excluded to protect.
  617. 00:36:24
    Of course, yeah. Figure the sample
  618. 00:36:28
    size is probably large enough at this
  619. 00:36:29
    point that we can have some anonymity in
  620. 00:36:32
    here There are, um, uh, there are,
  621. 00:36:36
    um,
  622. 00:36:41
    Maybe three of them that come to mind
  623. 00:36:44
    are the first one was a young man with
  624. 00:36:48
    an incurable disease or coup, had a
  625. 00:36:52
    clavus chordoma and tested our skills
  626. 00:36:57
    and and make air family centric around
  627. 00:37:00
    the region, The areas that we've talked
  628. 00:37:02
    about The second one would be
  629. 00:37:10
    an idiopathic subtract nor hemorrhage
  630. 00:37:14
    patient who
  631. 00:37:18
    had 'em He
  632. 00:37:20
    was a diabetic, and he probably had
  633. 00:37:22
    microvascular disease, and at a parry
  634. 00:37:26
    ventricular bleeding point and filled
  635. 00:37:29
    his ventricles entirely with blood, and
  636. 00:37:32
    was comatose for a couple of weeks and I
  637. 00:37:39
    was challenged. Why many individuals as
  638. 00:37:41
    to how why do we keep putting in the
  639. 00:37:46
    ventricular drains into this gentleman?
  640. 00:37:49
    And and this was pre thrombolytic ce,
  641. 00:37:55
    and
  642. 00:37:58
    after about ten drain, sir, he finally
  643. 00:38:01
    had a a functioning Csf flow system
  644. 00:38:04
    again, I woke up and went back to work,
  645. 00:38:08
    cause a,
  646. 00:38:11
    a very important to productive
  647. 00:38:14
    salesperson for a major company agent at
  648. 00:38:18
    a national presence, and eventually
  649. 00:38:20
    when he retired, became a a patient
  650. 00:38:23
    advocate, and Ncc you volunteer a lot
  651. 00:38:28
    and
  652. 00:38:30
    convince me that the number one blood in
  653. 00:38:34
    the ventricles system is bad and two.
  654. 00:38:41
    If you can get rid of it,
  655. 00:38:44
    maybe patients will survive, even
  656. 00:38:46
    though what I was taught in residency is
  657. 00:38:51
    if you have a grade four in a
  658. 00:38:53
    ventricular hemorrhage, you're dead.
  659. 00:38:56
    So
  660. 00:38:58
    that helped with what was my belief
  661. 00:39:01
    system at the time that nihilism isn't
  662. 00:39:04
    good. Right And maybe a third one is a
  663. 00:39:10
    young woman
  664. 00:39:13
    who was a reporter who came in and
  665. 00:39:15
    status epilepticus and that was
  666. 00:39:23
    treated. Although, you know, we
  667. 00:39:27
    learned that you, well, we had already
  668. 00:39:30
    known, but we applied that just because
  669. 00:39:33
    someone doesn't have motor concomadence
  670. 00:39:37
    of seizure that they may still be
  671. 00:39:40
    seizing.
  672. 00:39:42
    So, we got her situation under control,
  673. 00:39:45
    but she didn't wake up for a month. And
  674. 00:39:51
    what do you do with a 25-year-old who's
  675. 00:39:56
    comatose, whose disease you don't
  676. 00:40:00
    understand? You don't know why she was
  677. 00:40:04
    seizing We had some hypotheticals.
  678. 00:40:10
    And
  679. 00:40:13
    most of the
  680. 00:40:17
    senior people in the hospital
  681. 00:40:21
    suggested that, again, things were
  682. 00:40:25
    in a severe situation that
  683. 00:40:31
    she showed no improvement, and
  684. 00:40:36
    that we probably should be offering
  685. 00:40:41
    supportive care or withdrawing care as
  686. 00:40:45
    she needed ventilation for, oh, three
  687. 00:40:49
    and a half weeks, close to a month.
  688. 00:40:52
    It looked like
  689. 00:40:55
    I had established myself in the
  690. 00:40:58
    treatment area in the area of viral
  691. 00:41:03
    encephalitis.
  692. 00:41:05
    It turned out we eventually found out
  693. 00:41:12
    she had lymphocytic chorio meningitis I
  694. 00:41:13
    had written
  695. 00:41:16
    co-written several papers on the natural
  696. 00:41:19
    history of undiagnosed viral meningitis.
  697. 00:41:24
    I took the non-neolistic perspective
  698. 00:41:26
    that she didn't have herpes, which I
  699. 00:41:31
    had been involved in developing the
  700. 00:41:35
    first antiviral that was successfully
  701. 00:41:39
    able to At least stop the progression of
  702. 00:41:42
    of rupees and several lightest, and and
  703. 00:41:46
    I pointed out to my
  704. 00:41:50
    elders, that are in the
  705. 00:41:55
    observed prognosis in a case series that
  706. 00:41:59
    we had published in Jama that the people
  707. 00:42:02
    with viral encephalitis who did the best
  708. 00:42:05
    were those that we weren't smart enough
  709. 00:42:07
    to diagnose a A and I shared the same
  710. 00:42:10
    information with the family and I. We
  711. 00:42:16
    have. It was unusual to get 'em our
  712. 00:42:18
    eyes on and critically ill patients,
  713. 00:42:21
    but we got several. I arise, and
  714. 00:42:24
    showed there was no sign of evolving
  715. 00:42:27
    injury to the cortex or white matter of
  716. 00:42:31
    from encephalitis, and I. I took the
  717. 00:42:36
    unpopular view that it is. And in
  718. 00:42:42
    a 25-year-old, it was okay to support
  719. 00:42:45
    her for a little while longer and see if
  720. 00:42:47
    she woke up. She did wake up. She over
  721. 00:42:53
    a year returned to a normal cognitive
  722. 00:42:57
    function. And now is a mother with
  723. 00:43:03
    children and is a productive member of
  724. 00:43:06
    society as an investment banker. Well,
  725. 00:43:11
    that's a great story and I think in many
  726. 00:43:13
    ways it summarizes what I think it means
  727. 00:43:16
    to be neuro-intensivists as I get
  728. 00:43:19
    further into this field which is sort of
  729. 00:43:23
    having a lot of humility when it comes
  730. 00:43:24
    to prognosis and uncertainty around it
  731. 00:43:28
    and fighting against nihilism I think
  732. 00:43:31
    that is, those are core competency use
  733. 00:43:34
    for neuro-intensivists.
  734. 00:43:37
    I agree completely and I think you
  735. 00:43:38
    stated it very nicely. Maybe we could
  736. 00:43:41
    go back to that second case and
  737. 00:43:43
    transition a little bit to talking about
  738. 00:43:47
    intracerebral hemorrhage and
  739. 00:43:48
    intraventricular hemorrhage 'cause it
  740. 00:43:49
    struck me that in that case, perhaps
  741. 00:43:52
    this was an inspiration for further work
  742. 00:43:54
    that you did and that led to the clear
  743. 00:43:57
    three trial and use of thrombolytics.
  744. 00:43:59
    And maybe we could talk a little bit
  745. 00:44:02
    about these problems and some of the
  746. 00:44:04
    exciting advances that are happening now
  747. 00:44:06
    So, clear three on which you were the
  748. 00:44:09
    PI for those listening was unfortunately
  749. 00:44:12
    a negative trial of thrombolytic therapy
  750. 00:44:15
    for intraventricular hemorrhage. I am
  751. 00:44:19
    interested to talk to you about this
  752. 00:44:21
    because one of the things I think is so
  753. 00:44:23
    fascinating about the study is that
  754. 00:44:24
    there were various endpoints and one of
  755. 00:44:26
    them was clearance of over 80 of the
  756. 00:44:30
    hemorrhage and in that subgroup of
  757. 00:44:31
    patients, they seem to actually do
  758. 00:44:34
    better. And I think we always have to
  759. 00:44:36
    be careful about subgroup analyses, but
  760. 00:44:40
    I. I'm kind of with you when you were
  761. 00:44:43
    describing the second patient. I, I
  762. 00:44:45
    think intraventricular hemorrhage is
  763. 00:44:46
    just a bet a bad thing to have, and I
  764. 00:44:48
    think clearance is probably good, But
  765. 00:44:51
    what have you learned from Clear three?
  766. 00:44:53
    And how do you put that into action
  767. 00:44:55
    clinically and and where do we go from
  768. 00:44:58
    here with the problem of
  769. 00:44:59
    intraventricular hemorrhage or
  770. 00:45:04
    the womb. The great series of questions
  771. 00:45:08
    on by would clarify maybe one point one
  772. 00:45:14
    billion in your
  773. 00:45:17
    question
  774. 00:45:20
    of
  775. 00:45:23
    beer. Three represents the fourth or
  776. 00:45:26
    fifth in a series of trials. We did.
  777. 00:45:30
    I'd call it neutral, not negative.
  778. 00:45:33
    When both of us were in medical school
  779. 00:45:37
    trials read the positive and negative
  780. 00:45:39
    that that's a A Wall Street Journal
  781. 00:45:44
    vision of a randomized clinical trials,
  782. 00:45:48
    and you know negative in that it didn't
  783. 00:45:51
    produce a blockbuster drug name a, but
  784. 00:45:57
    neutral with a point estimate of benefit.
  785. 00:46:01
    Is how I would probably characterize it
  786. 00:46:04
    and then when you put it into context of,
  787. 00:46:08
    and we didn't have primary treatments
  788. 00:46:12
    for really any neurologic disease in the
  789. 00:46:19
    nineteen seventies and by the by the
  790. 00:46:23
    eighties when we started neuro critical
  791. 00:46:25
    care, there were few and a cycle of
  792. 00:46:29
    year for her ps encephalitis, the some
  793. 00:46:31
    of the patients of which didn't need.
  794. 00:46:34
    Neuro critical care unit may be a good
  795. 00:46:37
    example of one of the firsts, and so
  796. 00:46:42
    are the clear story evolved
  797. 00:46:48
    from patients like the one I described,
  798. 00:46:51
    I
  799. 00:46:54
    have a neurosurgery resident who became
  800. 00:46:57
    a neuro critical care fellow and now
  801. 00:47:01
    teaches neurosurgery residents at Johns
  802. 00:47:03
    Hopkins, Neil Naf,
  803. 00:47:08
    and called me in the middle of the night
  804. 00:47:11
    and said he had an
  805. 00:47:15
    I C H patient with obstructive ivy age,
  806. 00:47:19
    and he'd put in to ventricular drains as
  807. 00:47:22
    well, each one clotted and couldn't
  808. 00:47:25
    drain, and the patient was hypertensive
  809. 00:47:29
    and appeared to have a cushing's reflex
  810. 00:47:33
    and. What would it be Ok if if he
  811. 00:47:40
    escorted in a little bit of Euro Kinase
  812. 00:47:44
    when he put in the neck strain of any
  813. 00:47:47
    said otherwise, I think this guy's
  814. 00:47:49
    gonna die and I said Okay makes sense.
  815. 00:47:55
    Triad and I came in the next morning and
  816. 00:48:01
    the man's blood pressure was under
  817. 00:48:03
    control and we rescan him and he no
  818. 00:48:10
    longer had a locked ventricular system
  819. 00:48:13
    and he'd he'd had some thrombolysis and
  820. 00:48:17
    there was a little bit of Csf that was
  821. 00:48:19
    draining, and so we we started doing
  822. 00:48:22
    that in an organized way, Neil Naf and
  823. 00:48:27
    Michael Williams, another trainee,
  824. 00:48:30
    who's now a professor. Have neurology
  825. 00:48:34
    and runs the hydrocephalus program at
  826. 00:48:37
    the University of Washington, and did
  827. 00:48:40
    all the hard work of defining a protocol,
  828. 00:48:45
    getting an F D, A I, n D, and we
  829. 00:48:50
    started a low dose a kinase program,
  830. 00:48:55
    which when you're a kinase was
  831. 00:48:59
    taken off the market for some production
  832. 00:49:01
    problems and contamination, and the
  833. 00:49:04
    production problems switched over to T P
  834. 00:49:06
    A and and we created a case series of
  835. 00:49:12
    and and this is an important, I think,
  836. 00:49:15
    and in the rise of clinical trials and
  837. 00:49:18
    neuro critical care, when you don't
  838. 00:49:20
    have a, have a treatment, a primary
  839. 00:49:24
    treatment, and you can do single single
  840. 00:49:30
    -arm studies in which you expose. all
  841. 00:49:33
    patients to treatment if it can be
  842. 00:49:35
    legitimately shown that it's in the
  843. 00:49:37
    benefit of that patient to be exposed.
  844. 00:49:41
    We did
  845. 00:49:43
    that and we had predictive algorithms
  846. 00:49:45
    that all of these patients died. So the
  847. 00:49:48
    clinical wisdom in the story I told you
  848. 00:49:51
    was more than wisdom, it had pragmatic
  849. 00:49:54
    data behind it And we showed that
  850. 00:50:01
    80 would live in this single arm study.
  851. 00:50:05
    And that became the predicate for an FDA
  852. 00:50:09
    orphan drug application, which required
  853. 00:50:13
    five submissions in order to get funded.
  854. 00:50:17
    And then it required special privileges
  855. 00:50:21
    from the FDA to switch from - we wrote
  856. 00:50:24
    it about urokinase, but urokinase was
  857. 00:50:29
    prohibited from being used for two years.
  858. 00:50:33
    So, we switched it to
  859. 00:50:36
    TPA and started first the safety trial
  860. 00:50:41
    in which we learned a lot about how EVDs
  861. 00:50:46
    can create brain bleeding and make it
  862. 00:50:49
    worse, the interaction between the
  863. 00:50:52
    treatment and the EVD and how to manage
  864. 00:50:58
    that situation and showed that it was
  865. 00:51:02
    safer than doing nothing, and then some
  866. 00:51:05
    dose finding studies, and then finally
  867. 00:51:08
    clear three. Now, there have been
  868. 00:51:16
    four or five registries since then, and
  869. 00:51:25
    neuro-intensivist Erlangen, Joji
  870. 00:51:26
    Kuramatsu has put together all that data
  871. 00:51:27
    with the clear three data. And with the
  872. 00:51:32
    help of Wendy's the eye and their paper
  873. 00:51:36
    in Jama Open is now fifteen hundred
  874. 00:51:40
    patients, and, and although it's not a
  875. 00:51:43
    randomized controlled trial is what's
  876. 00:51:45
    called an individual patient of analysis
  877. 00:51:50
    or meta analysis, but patient by
  878. 00:51:54
    patient, not trial by trial, and a lot
  879. 00:51:57
    of technical distinctions there,
  880. 00:52:01
    and it shows a clear statistically
  881. 00:52:05
    significant and ten percent absolute
  882. 00:52:09
    benefit in the proportion of patients
  883. 00:52:12
    that reach a rank of zero to three. I
  884. 00:52:16
    think there'll be a clear for trial
  885. 00:52:17
    eventually and and it also shows some
  886. 00:52:22
    interesting things. One thing that I
  887. 00:52:25
    thought was obvious. That turns out not,
  888. 00:52:28
    I thought it would only work when there
  889. 00:52:30
    was a small, I Ch. appears to work
  890. 00:52:32
    when they're big ICHs as well. And
  891. 00:52:36
    there's a benefit in that assessment of
  892. 00:52:40
    treating earlier.
  893. 00:52:43
    Got it. If I can ask, as you envision
  894. 00:52:48
    Clear 4, how would you distinguish
  895. 00:52:50
    itself from Clear 3, potentially, what
  896. 00:52:53
    would you do differently?
  897. 00:52:59
    We learned in
  898. 00:53:05
    Clear 2, the dose finding,
  899. 00:53:09
    pharmacokinetic
  900. 00:53:11
    study, and Clear 3. And I believe it's
  901. 00:53:16
    in others data as well, that we didn't
  902. 00:53:19
    fully understand drug delivery when we
  903. 00:53:23
    went through this program. And that,
  904. 00:53:28
    when there's a lot of blood in the
  905. 00:53:29
    ventricular system, you may have to
  906. 00:53:31
    deliver blood and a drug in more than
  907. 00:53:33
    one place. And
  908. 00:53:36
    Wendy's published, Wendy's EI. has
  909. 00:53:39
    published some nice studies with Holly
  910. 00:53:42
    Hinson, who now is, was in Oregon,
  911. 00:53:46
    and
  912. 00:53:48
    now is a
  913. 00:53:50
    leader in neurocritical care at UCSF,
  914. 00:53:53
    and has a
  915. 00:53:56
    research program of her own. They
  916. 00:53:59
    looked at bilateral catheters, and we
  917. 00:54:02
    think putting one catheter into the clot,
  918. 00:54:05
    like you do in
  919. 00:54:07
    MISTI, and one to drain the CSF, and
  920. 00:54:10
    having more than one place to deliver
  921. 00:54:14
    TPA, both gets the clot out faster and
  922. 00:54:16
    gets more of it out. And I think that's
  923. 00:54:19
    probably the thing that would
  924. 00:54:22
    distinguish a clear four, and that
  925. 00:54:24
    happens to be our plan for that.
  926. 00:54:29
    Any lessons from the early drain trial
  927. 00:54:31
    in subrockinine hemorrhage using lumbar
  928. 00:54:34
    drains that can be applied to
  929. 00:54:37
    intracerebral hemorrhage with IVH in
  930. 00:54:39
    your opinion?
  931. 00:54:43
    Yeah,
  932. 00:54:45
    I mean, the single biggest lesson is
  933. 00:54:46
    things you don't look for, you don't
  934. 00:54:48
    say.
  935. 00:54:51
    And
  936. 00:54:53
    a lot of us went through life saying if
  937. 00:54:56
    the ventricle is clear, we got all the
  938. 00:54:58
    blood out ignoring the basic anatomic
  939. 00:55:02
    fact that
  940. 00:55:06
    the lumbar CSF space has half of the CSF.
  941. 00:55:11
    And if you don't see it on a CT scan,
  942. 00:55:15
    you don't see that space on a CT scan,
  943. 00:55:17
    so you don't know if it's blood there or
  944. 00:55:19
    not. We'd known for a long time that
  945. 00:55:22
    after subarachnoid hemorrhage,
  946. 00:55:26
    you can have, blood products in the
  947. 00:55:29
    lumbar space for long periods of time.
  948. 00:55:36
    The
  949. 00:55:39
    group in
  950. 00:55:45
    Erlangen has pioneered in draining that
  951. 00:55:48
    space. We know from animal models that
  952. 00:55:54
    blood in the brain in blood around the
  953. 00:55:56
    brain and blood degradation products,
  954. 00:56:00
    whether they're degraded iron, degraded
  955. 00:56:06
    porphyrin eam,
  956. 00:56:09
    or degraded hemoglobin, all create an
  957. 00:56:12
    inflammatory problem for brain tissues.
  958. 00:56:17
    And they've clearly shown that
  959. 00:56:20
    recovery and perhaps the likelihood of
  960. 00:56:25
    Fibrosis in the Csf space, and and
  961. 00:56:27
    hydrocephalus, or improve by drainage,
  962. 00:56:31
    that said, it's a high skill procedure
  963. 00:56:35
    that not all people do well, and that
  964. 00:56:38
    the potentially exposes patients to
  965. 00:56:42
    bacterial meningitis, and done
  966. 00:56:46
    improperly exposes patients to
  967. 00:56:49
    compartment syndrome and or herniation,
  968. 00:56:54
    and it needs it. It should be tested
  969. 00:57:00
    evolved and have a procedure developed
  970. 00:57:03
    that people outside of
  971. 00:57:07
    Er erlang, and can I can easily do.
  972. 00:57:12
    I wonder. Is I think a lot of centers
  973. 00:57:14
    have started placing more lumbar drains
  974. 00:57:16
    and subtracting hemorrhage patients,
  975. 00:57:17
    and whether we may see me some
  976. 00:57:19
    indication creep over time into that. i
  977. 00:57:22
    see age population but I Hope we do I
  978. 00:57:25
    think there are two basic parts to doing
  979. 00:57:29
    it correctly you have to have the lumbar
  980. 00:57:32
    catheter in the ventricular catheter
  981. 00:57:36
    in place and you have to demonstrate
  982. 00:57:39
    that there's been enough ventricular an
  983. 00:57:43
    extra ventricular blood removal so that
  984. 00:57:46
    you're not going to develop a
  985. 00:57:47
    compartment syndrome and that the the
  986. 00:57:50
    pressures are stable and equal between
  987. 00:57:54
    the lumbar and and cranial spaces and
  988. 00:57:57
    then you have to have a really good anti
  989. 00:57:59
    sepsis including great nursing to make
  990. 00:58:04
    sure a patient doesn't expose themselves
  991. 00:58:07
    to infection by partially pulling the
  992. 00:58:10
    drain out agreed agreed well maybe we
  993. 00:58:13
    could move on and talk a little bit
  994. 00:58:15
    about misty three and then and then
  995. 00:58:17
    finish up and misty three of course You
  996. 00:58:21
    are the P I on another neutral city,
  997. 00:58:22
    but when we've learned so much from, I
  998. 00:58:24
    think, and do it right now or orchestra
  999. 00:58:28
    of all eagerly awaiting the results from
  1000. 00:58:30
    the enrich trial, which was a different
  1001. 00:58:33
    type of procedure, a mainly invasive
  1002. 00:58:35
    procedure for Ic H, and but again it I
  1003. 00:58:41
    think a lot of people have have sort of
  1004. 00:58:44
    seen a corollary between the Esc
  1005. 00:58:46
    ischemic stroke story in the icy, Each
  1006. 00:58:47
    story that we have some idea, and I
  1007. 00:58:50
    think Missy three has helped us with
  1008. 00:58:52
    this to figuring out what is a target
  1009. 00:58:55
    outcome for the procedure, which and
  1010. 00:58:57
    we've now infamous If you may be less
  1011. 00:58:59
    than fifteen Mil leaders, and generally,
  1012. 00:59:02
    and now we need to find new ways to
  1013. 00:59:05
    actually achieve that I would do. I
  1014. 00:59:08
    guess where where do you? Where do you
  1015. 00:59:10
    see all this going And I I, I, If you
  1016. 00:59:13
    could, If you could talk a little bit,
  1017. 00:59:15
    it may be also about timing of the
  1018. 00:59:16
    procedures you mentioned an Ivy age.
  1019. 00:59:18
    That timing seems to be important. Some
  1020. 00:59:21
    people have criticized Mister Three
  1021. 00:59:22
    because it did take some time using that
  1022. 00:59:25
    procedure to actually get the hematoma
  1023. 00:59:28
    down to its target and what do you see
  1024. 00:59:31
    as the future of minimally invasive
  1025. 00:59:33
    surgery for Ic age,
  1026. 00:59:36
    though that's only six were
  1027. 00:59:40
    recapitalised. Yeah, Yeah, thirty
  1028. 00:59:42
    years of my life, so I actually think
  1029. 00:59:48
    of those are great questions, and I
  1030. 00:59:52
    think they're the the right questions of
  1031. 01:00:00
    Misty, the misty series of studies,
  1032. 01:00:04
    and there were
  1033. 01:00:07
    three of a open label set of studies
  1034. 01:00:15
    organized by Ricardo Car, Who Palmer.
  1035. 01:00:21
    a MISTI-2 that was a dose finding, and
  1036. 01:00:23
    then a MISTI-3,
  1037. 01:00:28
    which I did with Assamawad and
  1038. 01:00:32
    Wendy Zi among, and Mario Zukarello
  1039. 01:00:36
    among many others. And both MISTI-2 and
  1040. 01:00:42
    MISTI-3, and in rich, all demonstrate
  1041. 01:00:47
    that what the public health epidemiology
  1042. 01:00:51
    studies show, that you're gonna do much
  1043. 01:00:54
    better if you have a small hematoma than
  1044. 01:00:56
    a large one. And what these three
  1045. 01:01:00
    surgical trials show is that you don't
  1046. 01:01:04
    have to judge small hematoma by the day
  1047. 01:01:08
    you present with bleed. It can be in
  1048. 01:01:11
    the first few days after the bleed The
  1049. 01:01:15
    next question is Um, oh. Is there a
  1050. 01:01:20
    time limit and when we look at our data
  1051. 01:01:24
    we find that it doesn't matter whether
  1052. 01:01:27
    you reduce the hematoma on day one or
  1053. 01:01:32
    day two, or even into day three, You
  1054. 01:01:36
    can do trial meta analyses, and then
  1055. 01:01:39
    they are equivocal. Some show no effect
  1056. 01:01:42
    of time, and others have pushed by
  1057. 01:01:47
    people who want to study time only have
  1058. 01:01:50
    suggested there could be. I say this is
  1059. 01:01:53
    an area where we don't know and we
  1060. 01:01:55
    should find out it's very important to
  1061. 01:01:58
    public health. Not all patients are
  1062. 01:02:01
    going to get to and a neuro critical
  1063. 01:02:06
    care unit and a neurosurgeon in day one,
  1064. 01:02:10
    and if there's benefit on day two, and
  1065. 01:02:12
    perhaps into day three or four, we
  1066. 01:02:15
    should know about that. Most of the
  1067. 01:02:18
    extrapolation suggests that the risk
  1068. 01:02:20
    benefit, and in the recent world, in
  1069. 01:02:24
    the cranial hemorrhage and conference,
  1070. 01:02:28
    and I actually asked this question of
  1071. 01:02:30
    the enrich people who who are advocates
  1072. 01:02:34
    for early, and there are good reasons,
  1073. 01:02:36
    and they say yes, They're surgery does
  1074. 01:02:38
    produce benefit on the second day, and
  1075. 01:02:42
    this is the first time I've heard that
  1076. 01:02:44
    group began to do to address this
  1077. 01:02:48
    problem up, so we need to answer that
  1078. 01:02:51
    question and that's one that we need to
  1079. 01:02:53
    answer in a misty. For. I think the
  1080. 01:02:58
    other question that
  1081. 01:03:02
    is important to answer directly or the
  1082. 01:03:04
    the primary one is to show that
  1083. 01:03:11
    taking the hematoma out does make a
  1084. 01:03:14
    difference beyond mortality. I'll point
  1085. 01:03:17
    out. And
  1086. 01:03:19
    if neuro critical care was cancer, then
  1087. 01:03:23
    clear was a positive study. He was a
  1088. 01:03:26
    positive study. Having this up all the
  1089. 01:03:28
    time on rounds Is we have. Are we hold
  1090. 01:03:30
    our child's to a much higher standard
  1091. 01:03:32
    than any other field right, and it may
  1092. 01:03:35
    be a mistake, and some of that comes
  1093. 01:03:37
    from a whole purpose of paternalistic
  1094. 01:03:41
    Neil Ism, Have we know what would be
  1095. 01:03:43
    good for the patients and Misty Three,
  1096. 01:03:46
    We asked the patients who survived,
  1097. 01:03:49
    including the rank and fours and fives
  1098. 01:03:52
    Of how did they feel about their
  1099. 01:03:53
    situation? Half of the rank and fives
  1100. 01:03:56
    are happy with their situation. Is it
  1101. 01:03:59
    true that you should be unhappy if you
  1102. 01:04:03
    need a total care and support. I would
  1103. 01:04:07
    think so today, and I'm sure most
  1104. 01:04:09
    people who who don't need that think so,
  1105. 01:04:12
    but half of the patients living in that
  1106. 01:04:14
    situation think otherwise. Know what
  1107. 01:04:19
    their spouses think and what what burden
  1108. 01:04:22
    is on the family. Those are other
  1109. 01:04:23
    questions that need to be answered. So
  1110. 01:04:26
    I think the big question and in the next
  1111. 01:04:29
    trial is is still the question is doing
  1112. 01:04:35
    something better than doing nothing and
  1113. 01:04:38
    enrich it to my mind. Didn't answer
  1114. 01:04:40
    that to bring the conversation around
  1115. 01:04:44
    the paper is at the New England Journal
  1116. 01:04:47
    of medicine, Alan Roper will probably
  1117. 01:04:50
    be the determining editor of four.
  1118. 01:04:53
    Whether or not it's published there. I
  1119. 01:04:55
    think it's going to be very important
  1120. 01:04:56
    for us to look at the data and Enrich is
  1121. 01:05:01
    a Basie, and trial, basie, and
  1122. 01:05:04
    designs are usually used for phase two
  1123. 01:05:08
    dose finding and treatment calibrating
  1124. 01:05:13
    studies. There is an indication.
  1125. 01:05:16
    Strong indication of benefit for one
  1126. 01:05:19
    subgroup, the low bar hematomas. There
  1127. 01:05:23
    is no and possibly negative benefit for
  1128. 01:05:27
    deep in misty. We saw benefit in the
  1129. 01:05:30
    deep subgroup point estimates of benefit.
  1130. 01:05:34
    A point estimate is not for benefit and
  1131. 01:05:37
    enrich. So there's much to be digested
  1132. 01:05:41
    their. We've taken the Misty three data,
  1133. 01:05:44
    and there's a nice paper in neurology
  1134. 01:05:47
    now doing a bayesian analysis on on
  1135. 01:05:50
    Misty three data. It's positive to have
  1136. 01:05:55
    a. We have to. If you're going to use
  1137. 01:05:58
    evidence to guide therapy, reject the
  1138. 01:06:01
    null hypothesis and
  1139. 01:06:05
    the enrich and trial design, and the
  1140. 01:06:09
    sample size only suggested benefit a
  1141. 01:06:12
    second Basie and design to show that.
  1142. 01:06:16
    The enrich patients are different from
  1143. 01:06:18
    doing nothing has not been done to
  1144. 01:06:22
    reject the null hypothesis that requires
  1145. 01:06:24
    a substantially higher number. There
  1146. 01:06:27
    are only one hundred patients in the low
  1147. 01:06:32
    bar hematoma category exposed to
  1148. 01:06:36
    treatment, compared to the I think
  1149. 01:06:39
    hundred and fifty controls that they
  1150. 01:06:41
    have, so we'll we'll see what others
  1151. 01:06:43
    say about whether or not this is
  1152. 01:06:46
    guideline changing. I don't think it is.
  1153. 01:06:49
    I think it's confirming of the messages
  1154. 01:06:51
    that are in Misty two and Misty three.
  1155. 01:06:56
    You mentioned some of the discordance
  1156. 01:06:58
    maybe between Missy and what we've
  1157. 01:07:00
    learned about enrich to fire, and in
  1158. 01:07:03
    terms of locations, and and do you
  1159. 01:07:05
    think ultimately I will be will be
  1160. 01:07:08
    talking about me? Be different types of
  1161. 01:07:10
    procedures for different human tumor
  1162. 01:07:12
    locations.
  1163. 01:07:17
    So pin up the good thing about Misty
  1164. 01:07:20
    Three is it's focused on the
  1165. 01:07:25
    investigative world on a definition of a
  1166. 01:07:28
    surgical task and making the hematoma
  1167. 01:07:31
    smaller, and if you look at the number
  1168. 01:07:33
    one factor, that's predictive of poor
  1169. 01:07:36
    outcome, it's hematoma size, Not
  1170. 01:07:38
    location location is about three or four
  1171. 01:07:42
    in a hierarchical assessment. That's
  1172. 01:07:45
    very bothersome to people like us who
  1173. 01:07:47
    trained as a neurologist to learn, you
  1174. 01:07:50
    know what each location in the brain
  1175. 01:07:51
    does and what are bad locations for
  1176. 01:07:55
    lesions, but we have to manage both
  1177. 01:07:59
    factors in the care of I Ch patients,
  1178. 01:08:02
    and volume reduction, which has been
  1179. 01:08:06
    accepted by almost everybody designing
  1180. 01:08:09
    trials, and by almost every
  1181. 01:08:12
    neurosurgeon as the goal for the task,
  1182. 01:08:15
    I think that should. Ideally remain the
  1183. 01:08:18
    main design element in a trial, which,
  1184. 01:08:21
    whether you use a Volkswagen like a
  1185. 01:08:25
    small, and usually not damaging Ibi D
  1186. 01:08:30
    catheter
  1187. 01:08:32
    or an A and a large brain path trocar,
  1188. 01:08:41
    that has a sixteen millimeter profile,
  1189. 01:08:44
    which may be damaging when you try to do,
  1190. 01:08:47
    inserted into the deep basil ganglia
  1191. 01:08:51
    that have many many small penetrating
  1192. 01:08:55
    arteries, and whether one is better
  1193. 01:08:58
    than another, I think should be judged
  1194. 01:09:03
    by the outcome of the patients, and the
  1195. 01:09:05
    intermediate variable is a surgical task.
  1196. 01:09:08
    There will always be a better tool.
  1197. 01:09:12
    Whether it's a better tool for
  1198. 01:09:14
    intensivists, or. or surgeons. And I
  1199. 01:09:18
    think we shouldn't get
  1200. 01:09:21
    distracted by the fact that new tools
  1201. 01:09:25
    will develop. Eight to test, does the
  1202. 01:09:29
    surgery do the task and did doing the
  1203. 01:09:33
    task alter the outcome?
  1204. 01:09:38
    Well, that's great. At the end of this,
  1205. 01:09:41
    with each of our guests, we have some
  1206. 01:09:43
    kind of quick hit questions to get a
  1207. 01:09:45
    little
  1208. 01:09:47
    more insight into how you think is an
  1209. 01:09:50
    intensus in your life outside the ICU.
  1210. 01:09:52
    Do you have any passions or hobbies
  1211. 01:09:55
    outside of neurology?
  1212. 01:09:58
    Yeah.
  1213. 01:10:01
    I like
  1214. 01:10:03
    skiing. I like tennis. I like swimming.
  1215. 01:10:08
    I like traveling. I like cooking I like
  1216. 01:10:12
    eating and cooking
  1217. 01:10:15
    And
  1218. 01:10:18
    I enjoy hiking and the outdoors great,
  1219. 01:10:23
    and you've mentioned it. It stayed in
  1220. 01:10:25
    neurology, Neuro cruel, curse Roger
  1221. 01:10:27
    career, but if you, if you had to pick
  1222. 01:10:29
    a different specialty, what other
  1223. 01:10:30
    specialty would you have liked to have
  1224. 01:10:32
    attempted?
  1225. 01:10:35
    But I've always said I'd like to be a
  1226. 01:10:38
    veterinarian because of it's even more
  1227. 01:10:41
    challenging the neuro critical care you
  1228. 01:10:44
    get and the whole body of an animal,
  1229. 01:10:49
    and you got a bunch of different kinds
  1230. 01:10:50
    of animals, including us human animals,
  1231. 01:10:54
    and and what special specialty would you
  1232. 01:10:56
    not like to do
  1233. 01:10:59
    do well
  1234. 01:11:05
    on Home of there isn't any bad specialty
  1235. 01:11:09
    of. Ah. I'm not.
  1236. 01:11:14
    I don't think I'm temperamentally. I
  1237. 01:11:18
    cut out to be a pediatrician. I'm
  1238. 01:11:22
    probably not temperamentally cut out to
  1239. 01:11:25
    be a psychiatrist or a psychologist. I
  1240. 01:11:30
    probably don't have the patience for
  1241. 01:11:31
    either of those specialties, and it is
  1242. 01:11:35
    is there a sound or smell and the icy
  1243. 01:11:37
    you that you that you really like or
  1244. 01:11:39
    that brings a sense of home for you
  1245. 01:11:43
    yell quiet,
  1246. 01:11:47
    and is there a sound or smell in the ice
  1247. 01:11:49
    you that you really hate.
  1248. 01:11:54
    I don't love Beta dine.
  1249. 01:11:57
    It's a good one and then just to wrap up
  1250. 01:11:59
    our conversation and what advice would
  1251. 01:12:02
    you give to a fellow who's about to
  1252. 01:12:04
    graduate,
  1253. 01:12:06
    and
  1254. 01:12:09
    there are more unsolved problems than
  1255. 01:12:11
    they resolve problems and realize that.
  1256. 01:12:16
    We don't know the answer most of the
  1257. 01:12:17
    time,
  1258. 01:12:19
    and that environment can make for a very
  1259. 01:12:25
    solid set of opportunities a solid
  1260. 01:12:27
    career to improve where we are today,
  1261. 01:12:31
    and I think it. I have one more
  1262. 01:12:34
    statement. Please please, and if you
  1263. 01:12:37
    don't do it, no one will.
  1264. 01:12:40
    That's right and that's a fi who human
  1265. 01:12:43
    canal. I remember when I was trying to
  1266. 01:12:46
    take my career path as a fellow, and he
  1267. 01:12:49
    said that to my advice needs, it will,
  1268. 01:12:51
    if not, if not you, who like, yeah,
  1269. 01:12:55
    I well, thank you so much for coming on
  1270. 01:12:57
    the podcast You've teased us a little
  1271. 01:13:00
    bit with With clear for a misty Four
  1272. 01:13:02
    were really excited to to see where
  1273. 01:13:05
    we're going in an ice agent aviation. I
  1274. 01:13:07
    think it's really exciting time to eat
  1275. 01:13:08
    part of our field, and and I'm very
  1276. 01:13:11
    appreciative to all that you've
  1277. 01:13:12
    contributed to it and adds helping us
  1278. 01:13:15
    take. Better care of our patients and
  1279. 01:13:18
    also giving us therapeutic options that
  1280. 01:13:20
    fight the nihilism that I you mentioned
  1281. 01:13:22
    earlier, so on, thank you so much for
  1282. 01:13:25
    your time and all your work, and
  1283. 01:13:27
    hopefully we can meet up for brunch in
  1284. 01:13:29
    Baltimore. One day. That's that's
  1285. 01:13:31
    wonderful though to talk to your neck
  1286. 01:13:34
    and I think you're doing some great
  1287. 01:13:37
    things and important areas of training
  1288. 01:13:41
    and pain control that will benefit all
  1289. 01:13:44
    of us. Alright, Thank you, Dr.
  1290. 01:13:46
    Hanley and so this wraps up their Neuro
  1291. 01:13:48
    critical care podcast App Perspective
  1292. 01:13:50
    series with Dr. Daniel Hanley and this
  1293. 01:13:53
    will be available anywhere you get your
  1294. 01:13:54
    podcasts, including Spotify in the
  1295. 01:13:57
    Apple Store and the Neuro Critical care
  1296. 01:13:58
    website and Semi are available, Thanks
  1297. 01:14:01
    again, Dr. Hanley by Nick Knight.