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Live at Annual Episode 5: Pharmacy Debates - The role of ketamine in status epilepticus

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Description

Following their debate on approaches to early phase management of refractory status epilepticus (RSE), Salia Farrokh, PharmD is joined by Caroline Der Nigoghossian, Neurocritical Care PharmD, Renad Abu-Sawwa, PharmD, and Gabe Fontaine, PharmD to explore the benefits and harms/risks of early ketamine administration in refractory status epilepticus, as well as the emerging literature for the use of ketamine in pediatric neurocritical care.

Contributors

  • Salia Farrokh, Pharm.D., BCPS, BCCCP

    Salia Farrokh, PharmD, BCPS, BCCCP is a neuro ICU clinical pharmacist specialist at Johns Hopkins Hospital. Dr. Farrokh received her PharmD degree from Saint John Fisher College, Wegmans School of Pharmacy in Rochester, NY. Her postgraduate training includes residencies in Critical Care and Pharmacy Practice at Yale-New Haven Hospital. Dr. Farrokh’s research interests include effective antiplatelet therapy in neuro intervention patients, optimal pain management in neuro ICU patients, and use of neurostimulants in this setting. Dr. Farrokh is passionate about training and precepting students and residents and is a certified ENLS trainer.

  • Caroline Der-Nigoghossian, PharmD, BCCCP

    NewYork-Presbyterian Hospital
    Columbia University Irving Medical Center

  • Gabe Fontaine, PharmD, MBA, BCPS

    Clinical Pharmacy Manager
    Critical Care, Intermountain Healthcare

  • Renad Abu-Sawwa

    Clinical Assistant Professor
    University of Florida

  1. 00:00:20
    Hi guys, thank you so much for joining
  2. 00:00:22
    us today. We're talking about the
  3. 00:00:24
    ketamine debate for status epilepticus.
  4. 00:00:26
    Here with me are Gabe, Renaud, and
  5. 00:00:29
    Caroline, and I'm Sally Furrok. I'm
  6. 00:00:32
    excited to ask some questions. We're
  7. 00:00:34
    gonna start with Gabe. Hi, Gabe. How
  8. 00:00:37
    are you doing? Oh, well, after that
  9. 00:00:39
    trouncing of a loss, a full 17 voted
  10. 00:00:43
    for me. I'm a little hurt right now,
  11. 00:00:45
    but I think I can power through it.
  12. 00:00:47
    Okay So your side of the debate was that
  13. 00:00:51
    do not use ketamine, and that was
  14. 00:00:53
    epileptic, is correct. Okay. That was
  15. 00:00:55
    my side, yes. Okay. So I am gonna
  16. 00:01:00
    kind of flip and switch kind of roles
  17. 00:01:02
    here and ask. I know that you had a
  18. 00:01:04
    very good conversation and actually a
  19. 00:01:06
    very strong, I think,
  20. 00:01:09
    story about why we shouldn't use
  21. 00:01:11
    ketamine. But if you had this very
  22. 00:01:14
    specific patient population that you
  23. 00:01:16
    would identify could possibly benefit
  24. 00:01:20
    very much so from ketamine and status,
  25. 00:01:22
    how would you describe that group? What
  26. 00:01:25
    is that kind of very clear patient
  27. 00:01:26
    population that you would think, you
  28. 00:01:28
    know what, this is it. This is like a
  29. 00:01:29
    perfect patient for ketamine, and I'm
  30. 00:01:32
    just gonna use it despite the shortage.
  31. 00:01:35
    Yeah, no, it's an excellent question.
  32. 00:01:36
    And I think there are sort of three time
  33. 00:01:39
    points in the treatment of status-up
  34. 00:01:40
    rectus where I really consider the use
  35. 00:01:43
    of ketamine. I think in the majority of
  36. 00:01:46
    patients, if they're moving towards
  37. 00:01:47
    intubation, pairing it with another
  38. 00:01:51
    anesthetic like propofol, for instance,
  39. 00:01:52
    and using both as part of that
  40. 00:01:54
    peri-intubation phase, and there's very
  41. 00:01:57
    little of any evidence to support that,
  42. 00:01:58
    but I do think really early ketamine may
  43. 00:02:01
    help mitigate some of the longer-term
  44. 00:02:04
    status epilepticus. I think the other
  45. 00:02:06
    patient where I consider it early are
  46. 00:02:10
    those patients who are human dynamically
  47. 00:02:11
    unstable. Despite describing
  48. 00:02:13
    cardiovascular collapse, Caroline did
  49. 00:02:15
    an excellent job showing that phenomenon
  50. 00:02:18
    is really in patients receiving
  51. 00:02:19
    conventional anesthetics like medazoleum
  52. 00:02:21
    and propofol along with ketamine. So
  53. 00:02:23
    it's nearly impossible to discern which
  54. 00:02:24
    of these is contributing to that. It's
  55. 00:02:26
    good to be mindful of it, but in those
  56. 00:02:28
    patients who are human dynamically
  57. 00:02:30
    unstable, I think putting them on
  58. 00:02:32
    ketamine or adding ketamine to their
  59. 00:02:33
    current profile in Caroline and her
  60. 00:02:34
    colleagues showed that their mean
  61. 00:02:35
    arterial pressure will increase over
  62. 00:02:37
    time over the course of five to seven
  63. 00:02:39
    days and their presser requirements will
  64. 00:02:41
    decrease later on Since that is
  65. 00:02:44
    epilepticus, those patients who you
  66. 00:02:46
    presume or have diagnosed press, that
  67. 00:02:49
    is a patient that I'm trying to get off
  68. 00:02:50
    propofol almost immediately and rapidly
  69. 00:02:53
    up titrate ketamine if they're not
  70. 00:02:54
    already on it. And so I think those are
  71. 00:02:56
    three of the areas where I'd really
  72. 00:02:57
    consider ketamine. Okay, great.
  73. 00:03:00
    Caroline, your turn. So you were
  74. 00:03:02
    talking about how ketamine is amazing
  75. 00:03:05
    and is the magic bullet and everyone
  76. 00:03:07
    should be on it. But I want to flip
  77. 00:03:10
    roles here and ask, is there a specific
  78. 00:03:13
    patient population that if this happen
  79. 00:03:17
    on rounds, you're going to say,
  80. 00:03:19
    absolutely not. This patient will not
  81. 00:03:21
    benefit from ketamine. If anything,
  82. 00:03:23
    they may actually, um, this may harm
  83. 00:03:25
    them. They may, um, you know, have
  84. 00:03:27
    some really, like significant
  85. 00:03:29
    complications from ketamine. The one
  86. 00:03:31
    patient population that I can think of
  87. 00:03:34
    is patients who are already having like
  88. 00:03:35
    hypercloemic metabolic acidosis, and
  89. 00:03:38
    they're like in shock. I think in that
  90. 00:03:40
    patient population, I would be careful
  91. 00:03:42
    starting ketamine. I would recommend
  92. 00:03:43
    not starting it because of like the
  93. 00:03:45
    genuine that is in like hydrochloride,
  94. 00:03:46
    then you can potentially worsen these
  95. 00:03:48
    patients metabolic acidosis. So I think
  96. 00:03:51
    in that patient population, from the
  97. 00:03:52
    side effect perspective, I would
  98. 00:03:53
    recommend not choosing ketamine. Would
  99. 00:03:56
    you be okay if your team said, well,
  100. 00:03:57
    we're just going to bolus, but, you
  101. 00:03:59
    know, very concentrated. Is that just
  102. 00:04:01
    the metabolic part of it with the
  103. 00:04:03
    dilution? Or do you think that the drug
  104. 00:04:05
    itself, let's say, if we're just using
  105. 00:04:07
    the high, you know, concentration
  106. 00:04:08
    boluses? Whether you're using like
  107. 00:04:11
    diluted or on diluted, I think you're
  108. 00:04:13
    going to have run into this problem.
  109. 00:04:14
    Because the diluted one is second. 9
  110. 00:04:17
    sodium chloride is a high chloride load
  111. 00:04:19
    on diluted one is like hydrochloride is
  112. 00:04:21
    a genuine so you're going to also have
  113. 00:04:22
    like your like your hyperfluoramic load.
  114. 00:04:24
    So I think like either or you're going
  115. 00:04:26
    to end up facing that and I've seen
  116. 00:04:29
    cases of like severe cardiovascular
  117. 00:04:31
    collapse with high doses of melanoma and
  118. 00:04:34
    ketamine where they are having like this
  119. 00:04:36
    very high hyperfluoramic metabolic
  120. 00:04:38
    acidosis. So in these situations, I'd
  121. 00:04:40
    rather like just down titrate
  122. 00:04:41
    anesthetics as soon as possible to
  123. 00:04:43
    prevent the cardiovascular collapse.
  124. 00:04:45
    Okay, cool. All right, we're not. I
  125. 00:04:48
    have a question for you that I think was
  126. 00:04:50
    also asked after the talk but I'm so
  127. 00:04:54
    interested to know what you think about
  128. 00:04:55
    this. There's this whole notion of
  129. 00:04:58
    early and super early and I think that
  130. 00:05:04
    Gabe and Carolyn kind of talked about oh
  131. 00:05:06
    maybe it's you know after the first
  132. 00:05:08
    agent were really rushing to use
  133. 00:05:11
    ketamine as before even like other
  134. 00:05:13
    anesthetics or you started before your
  135. 00:05:14
    first anesthetic.
  136. 00:05:17
    But I have a hard time mechanistically
  137. 00:05:20
    thinking about early and super early
  138. 00:05:22
    meaning, you know, this whole receptor
  139. 00:05:25
    down regulation, up regulations,
  140. 00:05:26
    probably already started, right? So
  141. 00:05:28
    even if we talk about after how many
  142. 00:05:31
    medications in that sequence of okay,
  143. 00:05:33
    like after your first benzod, that's
  144. 00:05:35
    the time, or even during the time that
  145. 00:05:37
    you're bolising your medaz, you should
  146. 00:05:39
    bolise your ketamine. Is that really
  147. 00:05:42
    still early? Like what is the timeline
  148. 00:05:45
    that we're looking at? I know in the
  149. 00:05:46
    pediatrician study that you mentioned,
  150. 00:05:48
    you said three days was in one of the
  151. 00:05:50
    studies, like that was kind of early,
  152. 00:05:51
    and then after that, it was considered
  153. 00:05:53
    late. So I feel like there's a huge
  154. 00:05:55
    discrepancy, and I feel like I still
  155. 00:05:57
    really don't understand if even like we
  156. 00:06:00
    should talk about hours, minutes, or
  157. 00:06:01
    we should talk about, oh, it's
  158. 00:06:04
    probably already too late, by the time
  159. 00:06:06
    that we diagnose the patient, right?
  160. 00:06:08
    What do you think about that? What's
  161. 00:06:09
    your kind of assessment and experience?
  162. 00:06:12
    So I think your question has a couple of
  163. 00:06:15
    different parts. I think the first
  164. 00:06:16
    thing I would address is while we talked
  165. 00:06:18
    about the receptor traffic king
  166. 00:06:21
    hypothesis and Caroline did a wonderful
  167. 00:06:22
    job talking about that, there's another
  168. 00:06:24
    hypothesis most of us know about, but
  169. 00:06:27
    we don't really, I don't think we talk
  170. 00:06:28
    about a lot. And that's 80 to 90 of the
  171. 00:06:31
    receptors in the brain are actually
  172. 00:06:34
    excitatory. And so when you think of
  173. 00:06:36
    SaaS, I've looked at this in the
  174. 00:06:37
    glutamate overload, it makes sense even
  175. 00:06:40
    early on to target that receptor group
  176. 00:06:45
    with medications. And so from that
  177. 00:06:47
    perspective, mechanically it makes
  178. 00:06:48
    sense to start ketamine. I wouldn't go
  179. 00:06:50
    as far as to say, start it instead of a
  180. 00:06:52
    benzo because that is our standard of
  181. 00:06:54
    care. But again, it's thinking about,
  182. 00:06:56
    okay, well, we use other ASMs that
  183. 00:06:59
    target glutamate and glutamate receptors
  184. 00:07:01
    and excitatory receptors second with
  185. 00:07:04
    non-benzo ASMs like Fennetown. Why not?
  186. 00:07:08
    Is that something that we need to think
  187. 00:07:10
    about? And there actually are centers I
  188. 00:07:13
    think that there's one in Italy where.
  189. 00:07:16
    there's talk about using ketamine
  190. 00:07:19
    boluses
  191. 00:07:21
    kind of after that initial load of a
  192. 00:07:24
    benzoyl or right after the first line
  193. 00:07:28
    non-benzo ASM
  194. 00:07:30
    as a bolus. And again, is that
  195. 00:07:33
    considered early? Is like you mentioned,
  196. 00:07:36
    is using ketamine as an infusion as your
  197. 00:07:39
    first anesthetic? Is that considered
  198. 00:07:41
    early? I think it's really more of a
  199. 00:07:46
    discussion of, at least in my
  200. 00:07:48
    experience, what clinicians are
  201. 00:07:50
    comfortable with, right? And so if you
  202. 00:07:52
    have clinicians that are maybe not
  203. 00:07:55
    comfortable using ketamine in general,
  204. 00:07:57
    it might be a bit of a stretch to
  205. 00:07:59
    suggest that we do a bolus, right?
  206. 00:08:01
    Instead of or right after the first
  207. 00:08:04
    non-benzo ASM.
  208. 00:08:06
    But that is something that in my
  209. 00:08:07
    experience, I've done a couple of times
  210. 00:08:10
    when I can when I can get the kind of go
  211. 00:08:13
    to to do that and it, you know, in our
  212. 00:08:15
    population. we are trying to,
  213. 00:08:20
    you know, mitigate the potential for
  214. 00:08:22
    intubation, I think it would be helpful.
  215. 00:08:24
    But even starting it as your first
  216. 00:08:27
    anesthetic, I mean, at that point,
  217. 00:08:29
    you know, the consistent thing that we
  218. 00:08:31
    see in the literature is that treatment
  219. 00:08:33
    delays are there, right? Regardless of
  220. 00:08:35
    whether you're talking about the first
  221. 00:08:36
    non-benzo ASM or the first anesthetic.
  222. 00:08:39
    And we, it's interesting because we all
  223. 00:08:41
    know that treatment delay is one of the
  224. 00:08:44
    independent factors that leads to poor
  225. 00:08:46
    outcomes, whether in pizza or adults.
  226. 00:08:48
    So why aren't we treating patients in
  227. 00:08:50
    general more aggressively? Whether that
  228. 00:08:52
    includes ketamine or not, I think is a
  229. 00:08:54
    discussion. But to be honest, I don't
  230. 00:08:56
    think the debate should be whether or
  231. 00:08:58
    not ketamine is considered a valid
  232. 00:09:00
    option in these patients. I think
  233. 00:09:02
    really what we need to study and what we
  234. 00:09:03
    need to figure out is when and how are
  235. 00:09:06
    we going to use it. That's the area
  236. 00:09:08
    that I would like to see more literature.
  237. 00:09:09
    Great, cool. Thank you guys. With
  238. 00:09:12
    that, we're ending our session today
  239. 00:09:16
    that you enjoy the rest of the meeting.
  240. 00:09:17
    Thank you.