Status ep||epncus, Stroke,

Increased IC
ArLhur Wheeler, Mu, lCC
rofessor of Medlclne
ulrecLor MlCu
vanderbllL unlverslLy Medlcal CenLer

Iacu|ty D|sc|osures
none
Learn|ng Cb[ecnves
Aer Lhls sesslon, learners wlll be able Lo:
- ueLecL and LreaL sLaLus epllepucus
- LvaluaLe and LreaL acuLe sLroke
- ulscuss Lhe beneLs and rlsks of lnLracranlal pressure
managemenL Lechnlques
"!"#"$% '()*'(+,$%" doesn't have a
dehn|non
AuLhor, year uenluon
8leck 1991 Conunuous selzure or no recovery > 20 mln
uodson 1993 > 30 mln or > 2 selzures wlLhouL recovery
1relman 1998 > 10 mln
LowensLeln 1999 > 3 mln or > 2 or more wlLhouL recovery*
Alldredge 2001 > 3 mln
Mayer 2002 > 10 mln or selzures wlLhouL recovery > 30
mln
Am Lpllepsy Soc 2008 > 10 mlnuLes or > 2 selzures wlLhouL full
recovery*
8rophy 2012 > 3 mlnuLes or > 2 selzures wlLhouL full
recovery*
(neurocrlucal Care Soc)
"-'./#,"0/1" doesn't have a dehn|non
Selzures > 2 hours
> 2 selzures / hour wlLhouL recovery
lallure of 2 anuconvulsanLs*
AssoclaLed wlLh encephallus, hyponaLremla, and
Loxln lnduced selzures
Mayer SA, Arch neurology 2002
Claassen !, Lpllepsla 2002
PolLkamp M, ! neurol neurosurg sych 2003
8rophy CM, neurocrlL Care 2012
Causes & rognosnc Iactors
ALu noncompllance
Alcohol
CvA
Pypoxla
CnS lnfecuon
Lncephallus
Pead Lrauma
ldlopaLhlc
Pypoglycemla
1oxlns, cycllc anudepressanLs, lldocalne, buproplon
ueLorenzo 8!, neurology 1996
Pesdorer uC, neurology 1998
8euer prognosls
Worse prognosls
* oor prognosuc facLors: Clder age, prolonged selzures, focal onseL, muluple
medlcal lllnesses
Irequency of se|zures and status
ep||epncus
Semng Se|zures Status keferences
Ceneral neuro lCu 4-13 0.4
Cddo M, CrlL Care Med 2009
8leck 1, CrlL Care Med 1993
lschemlc sLroke 3 1-10
Losslus M, Lur ! neuro 2002
velloglu S, SLroke 2001
LabovlLz u, neurology 2001
8aLeman 8, neurocrlL Care 2007
lnLracerebral
hemorrhage
10-30 1-21
assero S, Lpllepsla 2002
Sung C, neurol neurosurg sych 1989
ue8euck !, Clln neurol neurosurg 2007
kllpaLrlck C!, Arch neurol 1990
Subarachnold
hemorrhage
4-16 10-14
Classen !, neurology 2007
Messe S8, neurocrlL Care 2009
8ladln Cl, Arch neurol 2000
Pypoxlc-lschemlc
encephalopaLhy
3-40 30
krumholz A, neurology 1988
Levy uL, !AMA 1983
Snyder 8u, neurology 1980
8ossem AC, neurology 2009
1raumauc braln ln[ury 12-30 8-33
vespa M, CrlL Care Med 2007
1emkln n8, nL!M 1990
Plrsch L!, Lpllepsla 2004
rophy|acnc annconvu|sants?
Cond|non ALD kecommendanon keference
lschemlc sLroke no !auch LC, SLroke 2013
Subarachnold hemorrhage
ConLroverslal. AssoclaLed
wlLh worse ouLcomes ln 4
8C1s
8osegarL A!, ! neurosurgery
2007
lnLracerebral hemorrhage
noL recommended.
AssoclaLed wlLh worse
ouLcomes
Messe S8, neurocrlL Care 2009
naldech AM SLroke 2009
MorgensLern L8, SLroke 2010
MorgensLern L8, SLroke 2013
1raumauc braln ln[ury
7 days ln moderaLe or
severe 18l
So LL, neurology 1996
Anoxlc braln ln[ury no
Why are se|zures bad?
- MeLabollc acldosls
- 8esplraLory acldosls
- Pypoxemla
- Pypoglycemla
- PyponaLremla
- Asplrauon
lnLracranlal hyperLenslon
PyperLhermla
8habdomyolysls
- Pyperkalemla
- AcuLe renal fallure
- ComparLmenL syndrome
Why are se|zures bad?
PosplLal morLallLy:
convulslve sLaLus epllepucus 9-21
non-convulslve sLaLus 18-32
refracLory sLaLus 23-61
8raln lssues
- 8efracLorlness lncreases wlLh durauon
- LowensLeln uP, neurology 1993
- neuronal damage from prolonged selzures
- Plppocampus, CorLex, 1halamus
- Long Lerm cognluve lmpalrmenL
- krumholz A, neurology 1993
- Legrlel S, CrlL Care Med 2010
Ce|| b|o|ogy of status
- lnadequaLe gamma amlno buLyrlc acld
(CA8A) sumulauon
lnhlblLory funcuon
8lndlng slLes for anuconvulsanLs and anesLheucs
lnLernallzed durlng selzure
- Lxcesslve n-meLhyl-d asparLaLe (nMuA)
recepLor sumulauon
Selzure propagauon
neuronal damage
AnLagonlsLs: keLamlne, C, nC
2
,
LLCP, 1ramadol, uexLromeLhorphan
AgonlsLs: LLCP, 8enzodlazeplnes,
ropofol, 8arblLuraLes
In|na| treatment
- Alrway
- Cxygenauon
- LCC monlLorlng
- lv access wlLh naCl
- Check, or admlnlsLer glucose wlLh Lhlamlne
- 30-100 mL u30W, Lhlamlne 100 mg
- LlecLrolyLes, renal prole, ALu levels, A8C
- 1oxlcology sLudles lf perunenL
Aud|ence kesponse uesnon 1:
What |s the hrst ||ne drug therapy for
|n-hosp|ta| status ep||epncus?
A. los-phenyLoln
8. Lorazepam
C. LeveuraceLam
u. Mldazolam
L. ropofol

Neuromuscu|ar b|ockers
- uo noL LermlnaLe braln selzure acuvlLy!
- !"#$%$&' necesslLaLe conunuous LLC monlLorlng
- MlghL wanL Lo avold succlnylchollne
- 8habdomyolysls
- Pyperkalemla
- AlLernauve rocuronlum
I|rst ||ne pharmaco|og|ca| therapy = 8enzo
Lorazepam 0.1 mg/kg (4 mg)
- 60-89 lnlual conLrol

- Slower onseL?
- Less llpld soluble
- lewer recurrences
- ulsLrlbuuon L
1/2
2-3 hr
- 1lghLer CA8A blndlng
- 8efrlgerauon
ulazepam 0.13 mg/kg (10 mg)
- 42-76 lnlual conLrol
- lasLer onseL?
- Plgh llpld solublllLy
- 30 recurrence w/l 2 h
- 8apld redlsLrlbuuon
- veln lrrlLauon propylene glycol
- 8ecLal form avallable
1relman uM, nL!M 1998*
Alldredge 8k, nL!M 2001
Lepplk lL, !AMA 1983
rasad k, Cochrane 8ev 2003
Lecuveness of repeaLed doses unknown.
I|rst ||ne pharmaco|og|ca| therapy = 8enzo
LahaL L, 8M! 2000
Scou 8C, LanceL 1999
SllberglelL 8, nL!M 2012
Mldazolam 0.23 mg/kg (10mg)
- 42-76 lnlual conLrol
- lM, lv, nasal, buccal
- lasLer onseL?
- Plgh llpld solublllLy
- 8apld redlsLrlbuuon
re-hosplLal doslng lorazepam vs mldazolam
lnlual conLrol: 73 mldazolam vs. 63 lorazepam
14 lnLubaLed boLh groups
11 recurrence boLh groups
Second ||ne pharmaco|og|ca| therapy
henyLoln 18-20 mg/kg
- lnlual monoLherapy less
eecuve Lhan lorazepam 44
- lnfused drug acuve
- PypoLenslon & arrhyLhmlas
posslble wlLh rapld lnfuslon
(llmlL 30 mg/mln)
- noL dexLrose compauble
- ConLalns propylene glycol
- Alkallne pP
los-phenyLoln 13-20
phenyLoln equlvalenLs/kg
- ro-drug requlrlng converslon ~
13 mln
- PypoLenslon posslble-llmlL
lnfuslon Lo 100-130 mg/mln
- WaLer soluble
- uexLrose compauble
- 8easonable pP-velns
- lM doslng posslble
- up Lo 30x more cosLly
1relman uM, nL!M 1998
1h|rd ||ne pharmaco|og|ca| therapy:
Strong|y cons|der LLG mon|tor|ng
Clven ln ~1/3 of sLaLus cases
~43 glven vasopressors
~94 lnLubaLed
CuLcomes poor
urugs glven:
enLobarblLal
ropofol
henobarblLal
Conunuous 8Z lnfuslon

no dlerence ln subsLanual
morLallLy (48): propofol
vs. mldazolam vs.
penLobarblLal
enLobarblLal= fewer
breakLhroughs, more
hypoLenslon, longer
venulauon.
1relman uM, nL!M 1998
kowalskl 8C, CrlL Care Med 2012
Classen !, Lpllepesla 2002
1h|rd ||ne pharmaco|og|ca| therapy:
Strong|y cons|der LLG mon|tor|ng
ropofol 1-2 mg/kg load
- 2-10 mg/kg/hr
- CA8A sumulanL
- nMuA anLagonlsL
- ()%* dose aer >12 hours
selzure free
- uose relaLed hypoLenslon
- MeLabollc acldosls
- Pyperllpldemla-calorles
henobarblLal 20 mg/kg
- 100 mg/mln lnfuslon raLe
- 1-4 mg/kg/hr
- CA8A sumulanL
- 60 selzure conLrol
- ulsadvanLages:
- PypoLenslon
- ropylene glycol
- ueep long lasung sedauon
- 1 x 90-100 hr
SLecker MM, epllepsla 1998 1relman uM, nL!M 1998
1h|rd ||ne pharmaco|og|ca| therapy:
Strong|y cons|der LLG mon|tor|ng
enLobarblLal 3-13 mg/kg
load aL 100 mg/mln
- lnfuslon 1-4 mg/kg/hr
- PypoLenslon and
hypovenulauon rouune
- ropylene glycol
Mldazolam 0.2 mg/kg bolus
Lhen 0.173-1 mcg/kg/mln
- AdvanLage conunuous lnfuslon
wlLhouL hypoLenslon
- 1achyphylaxls
- Acuve meLabollLes
kumar A, CrlL Care Med 1992
A|ternate therap|es
valproaLe 20-40 mg/kg
- LlmlLed daLa
- 66 eecuveness vs. 42 for
phenyLoln
- lnfuslon raLe conLroverslal
- 8lsks:
- Pyperammonemla
- ancreauus
- 1hrombocyLopenla
- 430 lnhlblLor
LeveuraceLam (20 mg/kg )
- LlmlLed daLa
- lnlual reporL 67 Lermlnauon of
sLaLus
- Llule sedauon
- no slgnlcanL drug lnLeracuons
- Ad[usL for renal lmpalrmenL
- 1hrombocyLopenla?
Mlsra uk, neurology 2006
Agarwal 8k, Selzure 2007
Slnha S, neurology 2000
Llmdl nA, neurology 2003
eLers Cn, Selzure 2003
8uegg S, Lpllepsy & 8ehavlor 2008
larooq Mu, neurocrlL Care 2007
knake S, ! neurol neuros, sych 2008
"Sa|vage therapy"
- Lacoslmlde
- Mlnlmal daLa
- 200-400 mg (13-30 mln) lv
- PypoLenslon
- 1oplramaLe
- Mlnlmal daLa
- 200-400 mg (C only)
- MeLabollc acldosls
- 1lagablne
- lsourane
- Lldocalne
Claassen !, Lpllepsla 2002
1|me from LLG start to detecnon of hrst
se|zure
Suuer 8, CrlL Care Med 2013
LLG target
- Coal (lsoelecLrlc, bursL suppresslon, non-lcLerus) ls unknown
- 8ursL suppresslon"
- noL evldenced based
- assoclaLed wlLh more hemodynamlc compllcauons
- AssoclaLed wlLh lncreased morLallLy ln MlCu populauon
- WaLson , CrlL Care Med 2008, 36, 3171
- 1yplcal pracuce ls 24-48 of conLrol wlLh slow Laper
L|ectroencepha|ography for Intens|v|sts
When the shak|ng stops
- Conslder perslsLenL non-convulslve sLaLus
- 8eporLed ln ~30 of convulslng pauenLs wlLhln 24 hours
of Lermlnauon
- ueLorenzo 8!, Lpllepsla 1998
- 8-37 of unresponslve lCu pauenLs had non-convulslve
sLaLus
- rlverLera M, Lpllepsy 8es 1994
- 1owne A8, neurology 2000
- Conslder head C1
- Conslder lumbar puncLure
- Conslder rhabdomyolysls Lherapy
AUDILNCL kLSCNSL ULS1ICN 2
WnICn CI 1nL ICLLCWING IS 1nL
CNL LA8CkA1Ck 1LS1 kLUIkLD
8LICkL ADMINIS1kA1ICN CI 1A?
A. Sodlum
8. Clucose
C. roLhrombln ume
u. Calclum
L. Creaunlne

Stroke presentanons
Ischem|c > 70:
- lmmedlaLe maxlmal declL
- Cen presenL on awakenlng
- Peadache uncommon
- 1ranslenL precursor posslble
- < 3 Selzure
- usually alerL
- Cen hyperLenslve
nemorrhag|c 10-1S
- rogresslve declL
- Cen beglns durlng acuvlLy
- Peadache common
- WlLhouL warnlng
- < 30Selzure
- uecreased LCC common
- Severe hyperLenslon frequenL
- vomlung common
!auch LC, SLroke 2013 MorgensLern L8, SLroke 2013
Stroke m|m|cs: 3 of presentanons
- Pypoglycemla
- Mlgralne
- Selzures
- 1umor
- Abscess
- Wernlcke's
- Aoruc dlssecuon
- lnLoxlcauon
- ConLuslon / Lrauma
- Sodlum, elecLrolyLes
Wlnkler u1, SLroke 2009
Scou A, Ann Lmerg Med 2003
In|na| stroke eva|uanon
- use LMS-fasLer access
- Co Lo a sLroke cenLer
- key hlsLory:
LasL ume pauenL was normal
1rauma, surgery
Meds: anucoagulanLs, anuhyperLenslves,
anuconvulsanLs, dlabeLes 8x
- Lxam:
nlPSS
Cardlac exam, pulses
Slgns of llver dlsease, coagulopaLhy
!auch LC, SLroke 2013
In|na| stroke treatment
- Call code sLroke
- lv access
- Clucose*, check & correcL +/- Lhlamlne, elecLrolyLes,
creaunlne, hemoglobln, plaLeleLs, 1, Lroponln
- Cxygen LargeL saL > 94*
- 8onnlng CM, SLroke 1999
- 12 lead LCC and conunuous monlLor (a-b)
- Cx8 (noL recommended)
- Sagar C, Clln 8adlol 1996
non-conLrasLed head C1
M8l Ck buL noL worLh walung for
uWl sensluve and speclc-preferred for LranslenL sympLoms
llebach !8, SLroke 2002
kecommend m||estones
!auch LC, SLroke 2013
oss|b|e C1 resu|ts
- Pemorrhaglc
- arenchymal
- Subarachnold
- lschemlc
- Lmbollc
- Cccluslve
Cther |mag|ng hnd|ngs
Larly lnfarcL slgns (gray-whlLe dlerenuauon loss)
lnsular rlbbon slgn
Corucal rlbbon slgn
Cyrl swelllng
CperaLor dependenL and oen absenL
ArLerlal occluslon
Pyperdense vessel slgn (MCA)
oor prognosls
noL commonly seen
Ischem|c stroke treatment
- lv 1A (0.9 mg]kg max 90 mg)
ln < 3 hours
- 3 & 12 monLh morLallLy slmllar
beLween groups
- 17 vs. 20
- 24 vs. 28
- lCP 6.4 8x vs. 0.6 placebo
!
"!
#!
$!
%!
&!
'!
()! +,- ( ".! +,-
/

0
1
2
3
4
1
5
6
7

3
8
9
:
3
+
7
49;<
;61:753
Adams P, SLroke 2007
nlnuS, nL!M 1993
kwlaLkowskl 1C, nL!M 1999
1hrombo|ync benehts conhrmed
Sl1S-lS18 reglsLry < 3 hours n=11,863
1.6 lCP, 36 favorable ouLcome aL 90 days
LCASS l & ll 8C1s
A1LAn1lS A & 8 8C1s
1847 pauenLs LreaLed beLween 3-6 hours
C8 1.4* for excellenL ouLcomes and less dlsablllLy 3-4.3 h
C8 1.13 (ns) for excellenL ouLcomes 4.3-6 h
Clear beneL lf < 3 hours
Comp||canon 3-4.S hours 4.S-6 hours
1A lacebo 1A lacebo
lCP 3.9 1.7 6.9 1.0
ueaLh 13 12 13 10
Late(r) 1A
LCASS 3: 8C1 1A vs. placebo n=821, 8x 3-4.3 h
aer onseL
lCP 2 vs. 0.2
no dlerence ln morLallLy
LxcellenL" ouLcomes 32 vs. 43
lS1 3: 8C1 1A vs. placebo n=3033 8x up Lo 6 hr
lCP 7 vs. 1
no dlerence ln Pandlcap score"
More early deaLhs wlLh 8x buL equal aL 6 monLhs
Packe W, nL!M 2008
Sandercock , LanceL 2012
1hrombo|ys|s benehts dec||ne w|th nme
1
1.3
2
2.3
3
0-1.3 1.3-3 3-4.3 4.3-6
C
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d
a
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s

Symptom onset to 1reatment (hours)
IDA approved
w|ndow
Luropean
approved
w|ndow
ooled daLa n=1847:
LCASS l & ll 8C1s
A1LAn1lS A & 8 8C1s
Stroke gu|de||ne recommended (w|th caunons)
1A use based on ear|y C1 hnd|ngs
C1 I|nd|ngs
none
clear hypodenslLy or mass
eecL"
more subLle changes > 1/3
MCA"
SubLle changes < 1/3 MCA
SubLle changes > 1/3 MCA
PypodenslLy > 1/3 MCA
kecommendanons
1reaL
8 x rlsk of lCP: don'L LreaL (3h)
nlnuS, nL!M 1993
no hlgher rlsk & beneL: LreaL
aLel SC !AMA 2001
robably LreaL (6h)
robably noL LreaL (6h)
Do not treat
Larrue v, SLroke 1997
Packe W, !AMA 1993
1A contra|nd|canons ] caunons
Contra|nd|canons (a|| nmes)
- Pead Lrauma w/l 3 mo
- PC lCP / SAP
- Acuve hemorrhage
- ArLerlal puncLure
- laLeleLs < 100 x 10/L
- Peparln w/ elevaLed 11
- Warfarln w/ 1 >13 / ln8
>1.7
- Cral u1l or xa lnhlblLors w/
abnormal coags
- 8raln Lumor
- S8 > 183 mm Pg , u8 >
110 mm Pg
- Clucose < 30
Contra|nd|canons (> 3 hr)
Age > 80
nlPPSS > 23
Cral anucoagulanL use
regardless of coags
PC dlabeLes and prlor
sLroke
ke|anve exc|us|ons
- Ma[or surgery < 14 d
- Cl / urlnary
hemorrhage < 21 d
- Selzures aL onseL
- 8apldly lmprovlng
sympLoms
- Ml w/l 3 mo
- regnancy
Ischem|c Stoke 8 management w|thout
1A
- MosL lschemlc sLroke pauenLs hyperLenslve presenLauon
- 8 sponLaneously decllnes ln 28
- Cllverla-lllho !. neurol 2003
- PyperLenslon and hypoLenslon assoclaLed wlLh worse ouLcomes
- vemmos kn, ! Pum PyperLen 2004
- Ahmed n, SLroke 2009
- Casullo !, SLroke 2004
CPPlS n=179 3 arm 8C1, S8>160 8x labeLolol, llslnoprll,
placebo. 8 reducuon noL harmful, beuer 3 monLh morLallLy
(new Cv evenLs)
- ouer !l, LanceL neurology 2009
Consensus Ischem|c Stoke 8
management
- uo noL lower unless S8> 220 or u8 > 120 mmPg
unless:
- lf rLA candldaLe, Lhen geL 8 below 183/110
- lf Ml, dlssecuon, renal fallure, pulmonary edema presenL
Lhen reduce as needed and monlLor neuro funcuon
- lf no urgenL medlcal condluon and no 1A reduce by 13
and monlLor neuro funcuon
- Aer rLA keep 8 < 180/103
- !auch LC, SLroke 2013
- Safe Lo resLarL home anu-hyperLenslves w/l 24 hours.
Ischem|c stroke recommended ad[uncnve
treatments
- Conunuous LCC x 24 hours
- ASA wlLhln 48 hours of lschemlc sLroke lf 1A *#+
glven n=41,000: small beneL
- CublLz C, Cochrane revlew 2000
- uv1 prevenuon encouraged: lncldence 10-30
- 8LvAlL: lschemlc CvA enoxaparln superlor Lo 8lu ulP
- Sherman uC, LanceL 2007
- lever LreaLmenL noL harmful buL oen doesn'L work,
no demonsLraLed ouLcome beneLs
- kasner SL, SLroke 2002
- SchwarLz S, neurology 2000
- uen PerLog PM, LanceL neurol 2009
- !auch LC, SLroke 2013
Ischem|c stroke not recommended
ad[uncnve treatments
- 1lghL glucose conLrol
- ClS1-uk 8C1 (72-126 LargeL): no beneL
- Cray CS LanceL neurol 2007
- C8AS: posslble beneL wlLh severe sLroke and hlgher glucose
- !ohnsLon kC SLroke 2009
- 8ec's: Clucose 8x Lo malnLaln < 140-180 mg/dL
- !auch LC, SLroke 2013
- Pyperbarlc C
2
: no beneL
- Slnghal A8, neurol 8es 2007
- PypoLhermla, no beneL, numerous compllcauons
- Schwab S, SLroke 2001
- Correla M, Cochrane revlews 2000
- CPlL sLudy (www.anzcLr.org.au/Lrlal_) 2011
Ischem|c stroke not recommended
ad[uncnve treatments
Peparlnold anucoagulauon: noL beneclal
n=23,000
- CublLz C, Cochrane revlew 2004
- Pypervolemla and hemodlluuon: noL beneclal
- Asplund k, Cochran revlew 2002
- enLoxlfylllne noL beneclal
- Albumln supplemenLauon ?
- ALlAS 2 Plll Mu, SLroke 2011
Ischem|c stroke ad[uncnve treatments
- PemlcranlecLomy
- > 2/3 MCA dlsLrlbuuon aL < 6 hours ~80 morLallLy
- Age < 60
- 1lmlng uncerLaln (< 48 h)
- uLClMAL: n=38 8C1, 33 A88 for deaLh, more wlLh
beuer funcuon ln surglcal group
- uLS1ln?: n=32 8C1 41 A88 for deaLh, beuer funcuon
wlLh surgery
- PAMLL1: n=64 8C1 no survlval beneL
- PeAuull8S1: = n=26 8C1 no survlval beneL
Subramanlam S, 1he neurologlsL 2009
vahedl k, LanceL neurol 2007
AUDILNCL kLSCNSL ULS1ICN 3
WnICn CI 1nL ICLLCWING nAS 8LLN
SnCWN 1C IMkCVL CLINICAL CU1CCMLS
IN nLMCkknAGIC S1kCkL?
A. Puman recomblnanL lacLor vlla
8. Puman recomblnanL ussue plasmlnogen acuvaLor
C. 1reaLmenL of hyperLenslon
u. rophylacuc anuconvulsanLs
L. Surglcal evacuauon of cloL

nemorrhag|c stroke
- Luology:
- 80-90 hyperLenslve (decreaslng)
- 10-20 anucoagulanLs (lncreaslng)
- ? Amylold (lncreaslng)
- 8ole of sLauns unclear (SA8kL)
- ColdsLeln L8, neurology 2008
- ~1/2 wlll have lnLravenLrlcular blood
- ulagnosls: non-conLrasLed head C1 or M8l
- lnlual LreaLmenL:
- A8C's
- AdmlL Lo an lCu (nlCu lf posslble)
- ulrlnger Mn, CrlL Care Med 2001
LnlargemenL assoclaLed wlLh poorly
conLrolled dlabeLes & hyperLenslon
nemorrhag|c stroke
LnlargemenL:
~40 over 3 hours
~73 over 6 hours
kazul S, SLroke 1996
WlllmoL CS, PyperLenslon 2004
Ldema peaks day 3-7
LnlargemenL &
selzures predlcL
deaLh
Mayer S neurology 1994 Cebel !M, SLroke 2002
Contro| 8
romote c|omng
Contro| g|ucose
Lvacuate c|ot
Annconvu|sants
8 contro| |n ICn
- PyperLenslon ls bad > 160, 173, 200 mmPg.
- Chwakl k, SLroke 2004
- lu[ll ?, SLroke 1998
- kazul S, SLroke 1997
- WllmoL M, PyperLenslon 2004
- ln1L8AC1: 8C1 lowerlng S8 < 180 or < 140 w/l 6 hours (labeLolol)
n=404 (296 evaluable) MA 12 mmPg lower ln lnLenslve group
lnLense Lherapy group: less edema and hemaLoma growLh
no cllnlcal ouLcomes reporLed (ln1L8AC1 2)
Anderson CS, SLroke 2010, 41
A1ACP: 8C1 lowerlng S8 <200, < 170, or < 140 w/l 6 hours (nlcardlplne) n=60
Medlan 8 reducuon 62 mmPg [ 6 hours
Lower x'ule: smaller cloL, less edema, beuer 3 monLh funcuon
ureshl Al, Arch neurol 2010
A1ACP-ll: ongolng
rhVIIa for ICn
- hase llb: placebo, 40, 80,
120 mcg/kg
- n=399 LreaLed w/l 3 hrs
- 8leed volume reduced by 3.3,
4.3, 3.8 mL vs. placebo.
- Severe dlsablllLy ln: 69
placebo vs. 33, 49, 34
- Serlous Lhrombosls ln 2
placebo vs. 7 LreaLed.
Mayer SA, nL!M 2003
IAS1 study rhVIIa for ICn
- hase lll: placebo, 20 or 80
mcg/kg
- n=841 LreaLed w/l 3 hrs
- 8leed volume reduced by
2.6, 3.8 mL vs. placebo.
- 8ad ouLcomes ln: 24
placebo vs 26, 29
LreaLed
- Serlous Lhrombosls ln 8
placebo vs. 9, 10 LreaLed.
- Concluslon: noL helpful
Mayer SA, nL!M 2008
Anncoagu|ant reversa|
roLhrombln complex concenLraLes
8apld normallzauon of anucoagulanL assoclaLed
hemorrhage
Lesslnger CA, Am ! PemaLol. 2008
vlLamln k + ll vs. roLhrombln complex
CC: lasLer correcuon wlLh smaller volume lnfused
no dlerences ln cllnlcal ouLcomes
ablnger l, neurology 2011
8oulls nM, neurosurgery 1999
A1CP Lrlal laLeleL Lransfuslon for anu-plaLeleL
agenLs (ongolng). lnvesugauonal
nemorrhag|c stroke other treatments
- AnuconvulsanLs: noL recommended
- 10-30 rlsk of selzure & ouLcome worse wlLh cllnlcal selzures
- assero S, Lpllepsla 2002
- vespa M, neurology 2003
- rophylacuc anu-convulsanLs = no beuer, maybe worse
ouLcomes
- Messe S8 (CPAn1) neurocrlL Care 2009
- SLerolds-dlscouraged by all organlzauons
- oungvarln n, nL!M 1987
- 1ellez P, SLroke 1973
- lever reducuon / hypoLhermla: noL LesLed
- lC monlLorlng: conslder for:" CCS < 9, hydrocephalus,
lvP, or exam suggesung hernlauon
- MorgensLern L8, SLroke 2013
nemorrhag|c stroke other treatments
- Clucose conLrol: avold hypoglycemla"
- MorgensLern L8, SLroke 2013
- v1L prevenuon: yes
- Llasuc sLocklngs noL suclenL
- LacuL k, neurlology 2003
- Peparln safe and eecuve sLarLed > day 2, safe buL noL eecuve sLarLed
day 4, or 10
- uennls M, LanceL 2009
- 8oeer A, ! nerol neurosurg sych 1991
- ulckman u, klln Wochenschr 1988
Pemodlluuon: no
- lLallan AcuLe SLroke SLudy, LanceL 1988
- MannlLol / hyperLonlc naCl, glycerol: no
- Mlsra uk, ! neurol Scl 2003
- ?u ?L, SLroke 1992, 23: 967
nemorrhag|c stroke surg|ca| treatments
- Cerebellar hemorrhage ouLcomes beuer lf cloL >3 cm or lf
bralnsLem compresslon or hydrocephalus
- krlllos 8W, neurosurgery 2001
- Morloka ! Surg neurol 2006
- 8C1 for supra-LenLorlal bleed: S1lCP" Lrlal
- no overall dlerence ln survlval or funcuon n=1033
- ? beneL wlLh lobar cloL w/l 1 cm of surface or lobar bleed w/CCS > 9
- robably harmful lf CCS < 8 or deep cloL
- Menelow Au ,%*-)+. 2003
- 8C1 sLereoLacuc caLheLer dellvered rL1A vs. medlcal Lherapy:
MlS1lL ll" n=118
- SlgnlcanL reducuon ln cloL slze and perl-cloL edema
- unclear cllnlcal beneL
- Mould WA, SLroke 2013
Aneurysma| subarachno|d hemorrhage
Cllp or coll
uelayed cerebral lschemla common:
Large arLery vasospasm
lmpalred cerebral auLo-regulauon
volume depleuon
MeLa-analysls: no evldence 1rlple P"
hemodlluuon, hyperLenslon, hypervolemla ls
beneclal
uankbaar !W, CrlL Care 2010
Aud|ence kesponse uesnon 4
Wh|ch of the fo||ow|ng treatments
usua||y does not reduce |ntracran|a|
pressure?
A. CorucosLerolds
8. MannlLol
C. Pypervenulauon
u. PyperLonlc sallne
L. Llevauon of Lhe head of Lhe bed

Monroe ke|||e hypothes|s = Monroe
Doctr|ne
- Skull = xed conLalner
- 1hree ulds
- Cerebrosplnal uld
- 8lood
- 8raln (80 waLer)
- 1herapy should LargeL cause of lC
elevauon:
- CbsLrucuve hydrocephalus: remove
CSl / shunL
- Mass: 8emove Lumor or cloL
- Cellular edema: shrlnk cells
Cerebra| perfus|on
Cerebral perfuslon pressure (C) = MA-lC, goal 30-70
Measures to reduce IC
- CravlLy ls always on: elevaLe PC8 Lo 30
o
- leldman Z, ! neurosurg 1992
- revenL [ugular veln obsLrucuon / lower
Cv
- ChesLnuL 8M, Lmerg Clln nA 1997
- revenL selzures-prophylacuc phenyLoln
x 7 days ln Lrauma
- 1emkln n8, nL!M 1990
- SchlerhouL C, Cochrane revlew 2001
Measures to reduce IC
Pypervenulauon
- 8educes blood ow & volume from
vasoconsLrlcuon of normal braln.
- /)01#"%"' (mlnuLes Lo an hour)
- A bad ldea lf noL a brldge Lo somewhere
- undo gradually as soon as feaslble
- SLocchem n, ChesL 2003
- Curley C, Crlucal Care Med 2010
Csmo|ar agents to reduce IC
- 8equlre lnLacL blood braln barrler
- 8emove waLer from normal braln cells
- 8raln accommodaLes over ume by lncreaslng cellular
osmolarlLy
- Cnce hyperosmolarlLy ls esLabllshed lL musL be
malnLalned Lhen slowly reversed.
- Cbvlously avold hypoLonlc ulds
- no clear daLa Lo recommend one agenL over anoLher
- lrancony C, CrlL Care Med 2008
- 8opper AP, nL!M 2012
Csmo|ar measures to reduce IC
- MannlLol 0.23-1 gm/kg q 2-4 hr
- Acuons
- vasoconsLrlcuon
- Pemodlluuon
- Csmouc dlureuc
- lnLravascular volume depleuon
- Pyperchloremlc alkalosls
- Lowers CSl producuon
- CnseL 10-13 mlnuLes, max eecL aL 20-60 mlnuLes
- 8euer CS, kldney lnL 1997
- 1argeL: osmolarlLy 320
- 1oxlclLy: acuLe renal fallure (> 200 gm/day)
- Wakal A, Cochrane revlew 2007
- McCraw C, neurosurgery 1983
- 8opper AP, nL!M 2012
Csmo|ar measures to reduce IC
- PyperLonlc sallne: 3 ~130 mL
- Acuons
- volume expander
- Csmouc waLer Lransfer
- 1oxlclLy
- ulmonary edema
- Pyperchloremlc acldosls
- veln sclerosls
- 1argeL: osmolarlLy 320, na 130
- ureshl Al, neurosurgery 1999
- WhlLe P, AnesLh Analges 2006
- 8opper AP, nL!M 2012
Measures to reduce IC
- CorucosLerolds #*&' eecuve ln Lumoro-genlc edema
- Cuun P, Semln Cncol 1973
- 8raakman 8, ! neurosurg 1983
- Cooper 8, ! neurosurg 1979
- C8ASP lnvesugaLors, LanceL 2004
- 8arblLuraLes: lower lC buL no ouLcome beneL and oen cause
hypoLenslon
- Ward !u, ! neurosurgery 1983
- 8oberLs l, Cochrane revlew 2000
- Sedauon
- neuromuscular blockade
- lever suppresslon
unproven beneL
Cran|otomy for e|evated IC
8C1 18l wlLh hlgh lC n=133
Cooper u!, nL!M 2011
Summary of key o|nts
- 1reaL sLaLus epllepucus aggresslvely and suspecL non-
convulslve selzures aer Lhe shaklng sLops.
- 8ush Lo geL a C1 for all sLroke vlcums and lf lschemlc,
glucose noL low, < 3 hours, and safe, glve 1A.
- lnLracranlal hemorrhage ls Lerrlble and oLher Lhan
anucoagulanL reversal has no good LreaLmenL.
- Sklp hypervenulauon for elevaLed lC unless you have a
denluve follow up LreaLmenL.
kecommended kead|ng and Add|nona|
kesources
- Marlnl !!, Wheeler A, Crlucal Care Medlclne Lhe essenuals.
2010 ChapLer 34 neurologlcal Lmergencles.
- 8rophy CM, Culdellnes for Lhe evaluauon and managemenL
of sLaLus epllepucus. neurocrlL Care 2012 17: 3.
- MorgensLern !C, Culdellnes for ManagemenL of SponLaneous
lnLracranlal hemorrhage. SLroke 2010, 41: 2108.
- !auch LC, Culdellnes for Lhe early managemenL of pauenLs
wlLh lschemlc sLroke. SLroke, 2013, epub
- Curley C, eL al. Pypocapnla and Lhe ln[ured braln. Crlucal Care
Medlclne 2010 38:1348.
uesuons?