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Project: Ghana Emergency Medicine Collaborative
Document Title: Intracerebral Hemorrhage (ICH)
Author(s): William Barsan, MD
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Intracerebral	
  Hemorrhage	
  (ICH)	
  
William	
  Barsan,	
  MD	
  
Department	
  of	
  Emergency	
  Medicine	
  
Delldot,	
  Wikimedia	
  Commons	
  
IntroducAon	
  
•  Spontaneous	
  (atraumaAc)	
  ICH:	
  bleeding	
  into	
  
the	
  parenchyma	
  of	
  the	
  brain	
  that	
  may	
  extend	
  
into	
  the	
  ventricles	
  and	
  subarachnoid	
  space.	
  
•  10-­‐15%	
  of	
  all	
  cases	
  of	
  stroke	
  	
  
•  Mortality	
  
– 6	
  month	
  	
  	
  	
  30-­‐50%	
  
– One	
  year	
  	
  	
  50%	
  
Intracerebral	
  Hemorrhage	
  
•  Spontaneous,	
  non-­‐traumaAc	
  intracerebral	
  hemorrhage	
  
(ICH)	
  	
  is	
  a	
  significant	
  cause	
  of	
  morbidity	
  and	
  mortality	
  
throughout	
  the	
  world.	
  
•  	
  Excellent	
  medical	
  care	
  has	
  a	
  potent,	
  direct	
  impact	
  on	
  
ICH	
  	
  	
  morbidity	
  and	
  mortality,	
  even	
  before	
  a	
  specific	
  
therapy	
  is	
  found.	
  	
  	
  
•  The	
  overall	
  aggressiveness	
  of	
  ICH	
  care	
  is	
  directly	
  
related	
  to	
  mortality	
  from	
  this	
  disease.	
  	
  
•  AHA	
  has	
  new	
  guidelines	
  for	
  2010,	
  updated	
  from	
  2007	
  
ClassificaAon	
  
•  Primary	
  (80-­‐90%)	
  
– Spontaneous	
  rupture	
  of	
  small	
  vessels	
  damaged	
  by	
  
chronic	
  hypertension	
  or	
  amyloid	
  angiopathy	
  
•  Secondary	
  
– Vascular	
  abnormaliAes	
  (AVM,	
  aneurysm)	
  
– Tumor	
  
– Coagulopathy	
  
Pathophysiological	
  features	
  
•  Origin	
  of	
  hematoma	
  
– DegeneraAve	
  changes	
  in	
  the	
  vessel	
  wall	
  induced	
  
by	
  chronic	
  hypertension.	
  
– DilataAon	
  in	
  the	
  walls	
  of	
  small	
  arterioles.	
  
(microaneurysms)	
  
– Electron-­‐microscopical	
  study:	
  most	
  bleeding	
  occur	
  
at	
  the	
  bifurcaAon	
  of	
  affected	
  arteries.	
  
Where	
  do	
  they	
  occur?	
  
A.	
  Lobar	
  	
  
	
  
B.	
  Basal	
  ganglia	
  
	
  
C.	
  Thalamus	
  
	
  
D.	
  Brain	
  stem	
  (pons	
  
predominantly)	
  
	
  
E.	
  Cerebellum	
  
A
B
C	
  
D
E	
  
Looie496,	
  Wikimedia	
  Commons	
  
Predictors	
  of	
  Outcome	
  
•  Hematoma	
  volume	
  
•  GCS	
  
•  Intraventricular	
  hemorrhage	
  
•  Age	
  
•  ICH	
  locaAon	
  
•  Increased	
  cerebral	
  edema	
  
Source	
  Undetermined	
  
Source	
  Undetermined	
  
Mechanisms	
  of	
  Injury	
  
•  Early	
  hematoma	
  growth	
  
	
  	
  	
  	
  	
  	
  –	
  Hematoma	
  enlargement	
  
	
  	
  	
  	
  	
  	
  –	
  Increase	
  in	
  ICP,	
  Assue	
  disrupAon,	
  shear	
  
	
  forces	
  
•  Edema	
  and	
  toxic	
  effects	
  of	
  blood	
  products	
  
	
  	
  	
  	
  	
  	
  –	
  OsmoAcally	
  acAve	
  serum	
  products	
  
	
  	
  	
  	
  	
  	
  	
  –	
  Thrombin	
  
•  Inflammatory	
  response	
  
Hematoma	
  Expansion	
  
72%	
  have	
  some	
  hematoma	
  
expansion	
  over	
  the	
  first	
  24	
  hours	
  
	
  
	
  
38%	
  have	
  significant	
  (>33%)	
  
expansion	
  over	
  24	
  hours	
  
	
  
	
  
In	
  26%	
  of	
  these	
  cases,	
  the	
  
enlargement	
  is	
  within	
  1	
  hour	
  
Delldot,	
  Wikimedia	
  Commons	
  
DefiniAon	
  of	
  Classes	
  and	
  Levels	
  of	
  Evidence	
  Used	
  in	
  
AHA	
  Stroke	
  Council	
  RecommendaAons	
  
•  Class	
  I	
   	
   	
  Condi<ons	
  for	
  which	
  there	
  is	
  evidence	
  for	
  and/or	
  general	
   	
   	
   	
  
	
   	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  agreement	
  that	
  the	
  procedure	
  or	
  treatment	
  is	
  useful	
  and	
  effec<ve.	
  
•  Class	
  II	
   	
   	
  Condi<ons	
  for	
  which	
  there	
  is	
  conflic<ng	
  evidence	
  and/or	
  a	
   	
   	
   	
  
	
   	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  divergence	
  of	
  opinion	
  about	
  the	
  usefulness/efficacy	
  of	
  a	
  procedure	
  or	
  treatment.	
  
•  	
   	
   	
   	
  Class	
  IIa	
   	
  The	
  weight	
  of	
  evidence	
  or	
  opinion	
  is	
  in	
  favor	
  of	
  the	
  procedure	
  or	
  	
  	
  	
  
	
   	
   	
   	
  treatment.	
  
•  	
  	
  
•  	
   	
   	
   Class	
  IIb 	
  Usefulness/efficacy	
  is	
  less	
  well	
  established	
  by	
   	
   	
  
	
   	
   	
   	
  evidence	
  or	
  opinion.	
  
•  	
  Class	
  III	
   	
   	
  Condi<ons	
  for	
  which	
  there	
  is	
  evidence	
  and/or	
  general	
  agreement	
   	
   	
  
	
   	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  that	
  the	
  procedure	
  or	
  treatment	
  is	
  not	
  useful/effec<ve	
  and	
  in	
  some	
  cases	
  may	
  be	
  harmful.	
  
•  Therapeu<c	
  recommenda<ons	
  
•  	
  Level	
  of	
  Evidence	
  A	
   	
   	
  Data	
  derived	
  from	
  mulAple	
  randomized	
  clinical	
  trials	
  or	
   	
   	
  
	
   	
   	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  metaanalyses	
  
•  	
  Level	
  of	
  Evidence	
  B	
   	
   	
  Data	
  derived	
  from	
  a	
  single	
  randomized	
  trial	
  or	
   	
   	
   	
  
	
   	
   	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  nonrandomized	
  studies	
  
•  	
  Level	
  of	
  Evidence	
  C	
   	
   	
  Consensus	
  opinion	
  of	
  experts,	
  case	
  studies,	
  or	
  standard	
  of	
  	
  care	
  
•  	
  	
  Diagnos<c	
  recommenda<ons	
  
•  	
  Level	
  of	
  Evidence	
  A	
   	
   	
  Data	
  derived	
  from	
  mulAple	
  prospecAve	
  cohort	
  studies	
   	
   	
  
	
   	
   	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  using	
  a	
  reference	
  standard	
  applied	
  by	
  a	
  masked	
  evaluator	
  
•  	
  Level	
  of	
  Evidence	
  B	
   	
   	
  Data	
  derived	
  from	
  a	
  single	
  grade	
  A	
  study,	
  or	
  one	
  or	
  more	
   	
   	
  
	
   	
   	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  case-­‐control	
  studies,	
  or	
  studies	
  using	
  a	
  reference	
  standard	
   	
  
	
   	
   	
   	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  applied	
  by	
  an	
  unmasked	
  evaluator	
  
•  	
  Level	
  of	
  Evidence	
  C	
   	
   	
  Consensus	
  opinion	
  of	
  experts	
  
PresentaAon	
  Content	
  Areas	
  
•  	
  Neuroimaging	
  of	
  ICH	
  
•  	
  	
  Hemostasis	
  
•  	
  	
  Blood	
  pressure	
  management	
  	
  
•  	
  	
  InpaAent	
  management	
  and	
  prevenAon	
  of	
  secondary	
  injury	
  
•  	
  	
  Intracranial	
  pressure	
  	
  (ICP)/glucose/seizures/
hydrocephalus	
  	
  	
  
•  	
  	
  Surgical	
  treatment	
  of	
  ICH	
  	
  	
  
•  	
  	
  Intraventricular	
  hemorrhage	
  	
  
•  	
  	
  Withdrawal	
  of	
  technological	
  support	
  
•  	
  	
  PrevenAon	
  of	
  recurrent	
  ICH	
  
•  	
  	
  RehabilitaAon	
  and	
  recovery	
  
Neuroimaging	
  of	
  ICH	
  
	
  
Computed	
  tomography	
  (CT)	
  
scan	
  showing	
  Leg	
  
hemisphere	
  intracerebral	
  
hemorrhage	
  (ICH)	
  with	
  
intraventricular	
  	
  
extravasaAon	
  
Large	
  leg	
  intraparenchymal	
  hematoma	
  (ICH)	
   Source	
  Undetermined	
  
RecommendaAons	
  for	
  Neuroimaging	
  
in	
  ICH	
  
•  Rapid	
  neuroimaging	
  with	
  CT	
  or	
  MRI	
  is	
  
recommended	
  to	
  dis<nguish	
  ischemic	
  
stroke	
  from	
  ICH	
  	
  
•  CT	
  angiography	
  and	
  contrast-­‐enhanced	
  CT	
  
may	
  be	
  considered	
  to	
  help	
  iden<fy	
  
pa<ents	
  at	
  risk	
  for	
  hematoma	
  expansion	
  	
  
•  CT	
  angiography,	
  CT	
  venography,	
  contrast-­‐
enhanced	
  CT,	
  contrast-­‐enhanced	
  MRI,	
  
MRA	
  and	
  MRV	
  can	
  be	
  useful	
  to	
  evaluate	
  
for	
  underlying	
  structural	
  lesions	
  including	
  
vascular	
  malforma<ons	
  and	
  tumors	
  when	
  
there	
  is	
  clinical	
  or	
  radiologic	
  suspicion	
  	
  
Class	
  I,	
  Level	
  of	
  
Evidence	
  A	
  (Unchanged	
  
from	
  the	
  previous	
  
guideline).	
  
	
  	
  
Class	
  IIb,	
  Level	
  of	
  
Evidence	
  B	
  	
  	
  
Class	
  IIa,	
  Level	
  of	
  
Evidence	
  B	
  (New	
  
recommenda:on).	
  
	
  	
  
	
  
 
CTA	
  and	
  ICH:	
  
SPOT	
  sign	
  
•  CT	
  contrast	
  extravasates	
  into	
  
hematoma	
  
–  Spot	
  sign,	
  white	
  arrows	
  
•  May	
  predict	
  hematoma	
  
expansion	
  
Source	
  Undetermined	
  
Imaging	
  of	
  Underlying	
  Structural	
  
Lesions?	
  
•  CTA/CTV,	
  MRI	
  with	
  gadolinium,	
  MRA/MRV	
  can	
  all	
  be	
  useful	
  to	
  
evaluate	
  for	
  underlying	
  structural	
  lesions,	
  including	
  vascular	
  
malformaAons	
  and/or	
  tumors	
  
–  When	
  there	
  is	
  clinical	
  or	
  radiologic	
  suspicion	
  
AnAcoagulaAon	
  and	
  ICH	
  
AnAcoagulaAon	
  leads	
  to	
  more	
  
hematoma	
  growth	
  and	
  higher	
  
mortality	
  
Reverse	
  warfarin	
  promptly	
  and	
  
aggressively	
  
FFP	
  or	
  prothrombin	
  complex	
  
concentrates	
  (PCCs)	
  
IV	
  vitamin	
  K	
  
Faster	
  than	
  SQ/PO	
  but	
  a	
  small	
  
risk	
  of	
  anaphylactoid	
  reacAon	
  
Source	
  Undetermined	
  
 
Reversal	
  of	
  AnAcoagulaAon	
  in	
  ICH	
  paAents	
  
•  PaAents	
  with	
  a	
  severe	
  coagulaAon	
  factor	
  deficiency	
  or	
  severe	
  
thrombocytopenia	
  should	
  receive	
  appropriate	
  factor	
  replacement	
  
therapy	
  or	
  platelets,	
  respecAvely	
  	
  (Class	
  I,	
  C)	
  
•  PaAents	
  with	
  ICH	
  whose	
  INR	
  is	
  elevated	
  due	
  to	
  OAC’s	
  should	
  have	
  
their	
  warfarin	
  withheld,	
  receive	
  therapy	
  to	
  replace	
  vitamin	
  K-­‐
dependent	
  factors	
  and	
  correct	
  the	
  INR,	
  and	
  receive	
  intravenous	
  
vitamin	
  K	
  	
  (Class	
  I,	
  C)	
  
•  PCCs	
  have	
  not	
  shown	
  improved	
  outcome	
  compared	
  with	
  FFP	
  but	
  may	
  
have	
  fewer	
  complicaAons	
  compared	
  with	
  FFP	
  and	
  are	
  reasonable	
  to	
  
consider	
  as	
  an	
  alternaAve	
  to	
  FFP	
  (Class	
  IIa,	
  B)	
  
•  The	
  usefulness	
  of	
  platelet	
  transfusions	
  in	
  ICH	
  paAents	
  with	
  a	
  history	
  of	
  
anAplatelet	
  use	
  is	
  unclear	
  and	
  is	
  considered	
  invesAgaAonal	
  (Class	
  	
  IIb,	
  
B)	
  
 
PotenAal	
  Treatments	
  for	
  ICH:	
  
The	
  Problem	
  of	
  Hematoma	
  Expansion	
  
Source	
  Undetermined	
  
Hematoma	
  Expansion	
  is	
  Common	
  
•  Brol,	
  et	
  al.,	
  1997	
  
–  103	
  pts.,	
  prospecAve	
  observaAonal	
  study	
  with	
  serial	
  CT	
  
scanning	
  (baseline,	
  1	
  hr	
  and	
  20	
  hrs	
  following	
  ICH)	
  
–  26%	
  showed	
  >33%	
  enlargement	
  on	
  1	
  hr	
  CT	
  
–  38%	
  showed	
  >33%	
  enlargement	
  on	
  20	
  hr	
  CT	
  
–  Neurologic	
  deterioraAon	
  correlated	
  with	
  hematoma	
  
expansion	
  
•  Brol	
  T	
  et	
  al,	
  Stroke.	
  1997	
  Jan;28(1):1-­‐5.	
  
Recombinant	
  AcAvated	
  Factor	
  VII*	
  
•  rFVIIa,	
  NovoSeven©	
  
•  Used	
  for	
  hemophilia	
  
•  Induces	
  local	
  hemostasis	
  when	
  it	
  
binds	
  to	
  Assue	
  factor	
  
–  The	
  complex	
  can	
  acAvate	
  Factors	
  IX	
  and	
  
X	
  
–  Factor	
  Xa	
  helps	
  convert	
  prothrombin	
  to	
  
thrombin	
  
	
  *Not	
  FDA	
  approved	
  for	
  ICH	
  
Harmid,	
  Wikimedia	
  Commons	
  
“FAST”	
  Trials	
  
•  A	
  phase	
  II	
  randomized	
  trial	
  showed	
  that	
  treatment	
  with	
  rFVIIa	
  within	
  four	
  
hours	
  ager	
  ICH	
  onset	
  	
  
–  limited	
  hematoma	
  growth	
  	
  
–  improved	
  clinical	
  outcomes	
  relaAve	
  to	
  placebo	
  	
  
–  increased	
  frequency	
  of	
  thromboembolic	
  events	
  (7%	
  vs.	
  2%)	
  
•  A	
  subsequent	
  phase	
  III	
  study	
  comparing	
  placebo	
  to	
  20	
  μg/kg	
  and	
  80	
  μg/kg	
  
of	
  rFVIIa:	
  	
  
–  both	
  doses	
  diminished	
  hematoma	
  enlargement	
  
–  failed	
  to	
  show	
  differences	
  in	
  clinical	
  outcome	
  
–  Overall	
  serious	
  thromboembolic	
  adverse	
  event	
  rates	
  were	
  similar,	
  the	
  higher	
  rFVIIa	
  (80	
  
μg/kg)	
  group	
  had	
  significantly	
  more	
  arterial	
  events	
  than	
  placebo.	
  	
  	
  
•  The	
  authors	
  noted	
  imbalances	
  in	
  treatment	
  groups,	
  parAcularly	
  intraventricular	
  
hemorrhage	
  in	
  the	
  higher	
  dose	
  rFVIIa	
  group	
  
Mayer	
  SA,	
  et	
  al	
  for	
  the	
  FAST	
  Trial	
  InvesAgators.,	
  N	
  Engl	
  J	
  Med.	
  2008	
  May	
  15;358(20):2127-­‐37.	
  
Mayer	
  SA	
  for	
  the	
  FAST	
  Trial	
  InvesAgators.	
  	
  N	
  Engl	
  J	
  Med.	
  2005	
  Feb	
  24;352(8):777-­‐85.	
  
Factor	
  VIIa	
  
•  Factor	
  VIIa	
  can	
  limit	
  hematoma	
  expansion	
  in	
  non-­‐
coagulopathic	
  paAents,	
  but	
  also	
  increases	
  thromboembolic	
  
risk.	
  
–  rFVIIa	
  is	
  not	
  recommended	
  in	
  unselected	
  pa:ents	
  
•  rFVIIa	
  does	
  NOT	
  replace	
  clovng	
  factors,	
  even	
  though	
  INR	
  
normalizes	
  
–  rFVIIa	
  is	
  not	
  recommended	
  as	
  the	
  only	
  agent	
  to	
  reverse	
  
INR	
  in	
  ICH	
  pa:ents	
  
Mayer	
  SA,	
  et	
  al	
  for	
  the	
  FAST	
  Trial	
  InvesAgators.,	
  N	
  Engl	
  J	
  Med.	
  2008	
  May	
  15;358(20):2127-­‐37.	
  
Mayer	
  SA	
  for	
  the	
  FAST	
  Trial	
  InvesAgators.	
  	
  N	
  Engl	
  J	
  Med.	
  2005	
  Feb	
  24;352(8):777-­‐85.	
  
Blood	
  Pressure	
  and	
  ICH:	
  	
  
Is	
  it	
  safe	
  to	
  lower	
  BP	
  in	
  the	
  acute	
  
sevng?	
  
Saperaud,	
  Wikimedia	
  Commons	
  
 
INTERACT	
  	
  
•  404	
  ICH	
  pts,	
  randomized	
  into:	
  
– Target	
  SBP	
  of	
  140mmHg	
  within	
  1	
  hr	
  OR	
  
– Target	
  SBP	
  of	
  180mmHg	
  	
  
•  Trend	
  towards	
  lower	
  hematoma	
  growth	
  
•  No	
  increase	
  in	
  adverse	
  events	
  related	
  to	
  BP-­‐lowering	
  
•  No	
  differences	
  in	
  clinical	
  outcome/QOL	
  
– Not	
  powered	
  for	
  clinical	
  endpoints	
  
Anderson	
  CS,	
  et	
  al.	
  Lancet	
  Neurol.	
  2008;7(5):391-­‐399	
  
ATACH	
  
•  80	
  ICH	
  pts	
  
•  4-­‐Aer,	
  dose	
  escalaAon	
  of	
  IV	
  nicardipine-­‐based	
  
lowering	
  of	
  BP	
  
•  Confirmed	
  safety	
  and	
  feasibility	
  of	
  early	
  rapid	
  
BP	
  lowering	
  
Qureshi	
  AI,	
  et	
  al,	
  	
  for	
  the	
  ATACH	
  InvesAgators	
  Arch	
  Neurol.	
  2010	
  May;67(5):570-­‐6	
  
Summary	
  of	
  New	
  BP	
  Lowering	
  in	
  
ICH	
  Trials	
  
•  These	
  new	
  studies	
  have	
  shown	
  that	
  intensive	
  
BP	
  lowering	
  is	
  clinically	
  feasible	
  and	
  
potenAally	
  safe	
  
•  BP	
  targets,	
  duraAon	
  of	
  therapy	
  is	
  unknown	
  
•  No	
  studies	
  have	
  shown	
  clinical	
  benefit	
  so	
  far	
  
 
Blood	
  Pressure	
  RecommendaAons	
  
•  UnAl	
  ongoing	
  clinical	
  trials	
  of	
  BP	
  intervenAon	
  
for	
  ICH	
  are	
  completed,	
  physicians	
  must	
  
manage	
  BP	
  on	
  the	
  basis	
  of	
  the	
  present	
  
incomplete	
  efficacy	
  evidence	
  (Class	
  IIb,	
  C)	
  
•  In	
  paAents	
  presenAng	
  with	
  a	
  systolic	
  BP	
  of	
  
150-­‐220	
  mmHg,	
  acute	
  lowering	
  of	
  systolic	
  BP	
  
to	
  140	
  mmHg	
  is	
  probably	
  safe	
  (Class	
  IIa,	
  B)	
  
Recommended	
  BP	
  Treatment	
  Targets	
  
•  If	
  SBP	
  is	
  >200	
  mmHg	
  or	
  MAP	
  is	
  >150	
  mm	
  Hg,	
  then	
  
consider	
  aggressive	
  reducAon	
  of	
  blood	
  pressure	
  with	
  
conAnuous	
  intravenous	
  infusion,	
  with	
  frequent	
  blood	
  
pressure	
  monitoring	
  every	
  5	
  minutes.	
  	
  
•  If	
  SBP	
  is	
  >180	
  mmHg	
  or	
  MAP	
  is	
  >130	
  mm	
  Hg	
  and	
  there	
  
is	
  the	
  possibility	
  of	
  elevated	
  ICP,	
  then	
  consider	
  
monitoring	
  ICP	
  and	
  reducing	
  blood	
  pressure	
  using	
  
intermilent	
  or	
  conAnuous	
  intravenous	
  medicaAons	
  
while	
  maintaining	
  a	
  cerebral	
  perfusion	
  pressure	
  >	
  60	
  
mmHg	
  
Recommended	
  BP	
  Treatment	
  Targets	
  	
  
•  If	
  SBP	
  is	
  >180	
  mmHg	
  or	
  MAP	
  is	
  >130	
  mm	
  Hg	
  
and	
  there	
  is	
  not	
  evidence	
  of	
  elevated	
  ICP,	
  
then	
  consider	
  a	
  modest	
  reducAon	
  of	
  blood	
  
pressure	
  (eg,	
  MAP	
  of	
  110	
  mm	
  Hg	
  or	
  target	
  
blood	
  pressure	
  of	
  160/90	
  mm	
  Hg)	
  using	
  
intermilent	
  or	
  conAnuous	
  intravenous	
  
medicaAons	
  to	
  control	
  blood	
  pressure,	
  and	
  
clinically	
  reexamine	
  the	
  paAent	
  every	
  15	
  
minutes.	
  
InpaAent	
  Management:	
  Medical	
  
ConsideraAons	
  
•  IniAal	
  monitoring	
  and	
  management	
  of	
  ICH	
  paAents	
  should	
  
take	
  place	
  in	
  an	
  intensive	
  care	
  unit	
  with	
  physician	
  and	
  
nursing	
  neuroscience	
  intensive	
  care	
  experAse	
  	
  (Class	
  I,	
  B)	
  
•  Glucose	
  should	
  be	
  monitored	
  and	
  normoglycemia	
  is	
  
recommended	
  	
  (Class	
  I,	
  C)	
  
•  PaAents	
  with	
  ICH	
  should	
  have	
  intermilent	
  pneumaAc	
  
compression	
  for	
  prevenAon	
  of	
  venous	
  thromboembolism	
  in	
  
addiAon	
  to	
  elasAc	
  stockings	
  (Class	
  I,	
  B)	
  
•  Ager	
  documentaAon	
  of	
  cessaAon	
  of	
  bleeding,	
  low-­‐dose	
  
subcutaneous	
  low-­‐molecular-­‐weight	
  heparin	
  or	
  
unfracAonated	
  heparin	
  may	
  be	
  considered	
  for	
  prevenAon	
  
of	
  venous	
  thromboembolism	
  in	
  paAents	
  with	
  lack	
  of	
  
mobility	
  ager	
  1	
  to	
  4	
  days	
  from	
  onset	
  	
  (Class	
  IIb,	
  B)	
  
 
InpaAent	
  Management	
  of	
  PrevenAon	
  of	
  
Secondary	
  Brain	
  Injury:	
  Medical	
  ConsideraAons	
  
Seizures	
  and	
  An:epilep:c	
  Drugs	
  
•  Clinical	
  seizures	
  should	
  be	
  treated	
  with	
  anA-­‐epilepAc	
  
drugs	
  (Class	
  I,	
  A)	
  
•  ConAnuous	
  EEG	
  monitoring	
  is	
  probably	
  indicated	
  in	
  
ICH	
  paAents	
  with	
  depressed	
  mental	
  status	
  out	
  of	
  
proporAon	
  to	
  the	
  degree	
  of	
  brain	
  injury	
  (Class	
  II,	
  B)	
  
•  PaAents	
  with	
  a	
  change	
  in	
  mental	
  status	
  who	
  are	
  found	
  
to	
  have	
  electrographic	
  seizures	
  on	
  EEG	
  should	
  be	
  
treated	
  with	
  anA-­‐epilepAc	
  drugs	
  (Class	
  I,	
  C)	
  
•  ProphylacAc	
  anAconvulsant	
  medicaAon	
  should	
  not	
  be	
  
used	
  (Class	
  III,	
  B)	
  
Hydrocephalus	
  
•  Hydrocephalus	
  can	
  
accompany	
  ICH,	
  especially	
  
intravenAcular	
  rupture	
  	
  
	
  	
  	
  	
  (IVH)	
  
•  Elevates	
  ICP	
  
•  Results	
  in	
  early	
  or	
  delayed	
  
neurologic	
  deterioraAon	
  
Source	
  Undetermined	
  
Intracranial	
  Pressure	
  Treatment	
  
Algorithm	
  
	
  
Source	
  Undetermined	
  
CLEAR-­‐IVH	
  Trial	
  
•  52	
  pts	
  with	
  IVH	
  
•  Open-­‐label	
  	
  intra-­‐ventricular	
  rt-­‐PA	
  to	
  accelerate	
  
blood	
  clearance	
  and	
  lysis	
  
•  Adverse	
  events	
  
–  SymptomaAc	
  bleeding	
  4%	
  
–  Bacterial	
  ventriculiAs	
  2%	
  
–  30	
  day	
  mortality	
  17%	
  
•  Efficacy	
  requires	
  confirmaAon	
  before	
  use	
  of	
  
intraventricular	
  fibrinolysis	
  can	
  be	
  
recommended,	
  Phase	
  III	
  trial	
  in	
  progress	
  
ICP	
  Monitoring	
  and	
  Ventriculostomy	
  
•  PaAents	
  with	
  a	
  GCS	
  score	
  of	
  8	
  or	
  less,	
  those	
  with	
  clinical	
  
evidence	
  of	
  transtentorial	
  herniaAon,	
  or	
  those	
  with	
  
significant	
  IVH	
  or	
  hydrocephalus	
  might	
  be	
  considered	
  for	
  
ICP	
  monitoring	
  and	
  treatment.	
  A	
  CPP	
  of	
  50-­‐70	
  mmHg	
  may	
  
be	
  reasonable	
  to	
  maintain	
  depending	
  on	
  the	
  status	
  of	
  
cerebral	
  autoregulaAon	
  	
  (Class	
  IIb,	
  C)	
  
•  Ventricular	
  drainage	
  as	
  treatment	
  for	
  hydrocephalus	
  is	
  
reasonable	
  in	
  paAents	
  with	
  decreased	
  level	
  of	
  
consciousness	
  (Class	
  IIa,	
  B)	
  
•  Although	
  intraventricular	
  administraAon	
  of	
  rt-­‐PA	
  in	
  IVH	
  
appears	
  to	
  have	
  a	
  fairly	
  low	
  complicaAon	
  rate,	
  efficacy	
  and	
  
safety	
  of	
  this	
  treatment	
  is	
  uncertain	
  and	
  is	
  considered	
  
invesAgaAonal	
  (Class	
  IIb,	
  B)	
  
Surgical	
  Management	
  of	
  ICH	
  
STICH	
  Trial	
  
•  902	
  ICH	
  pts	
  randomized	
  trial	
  of	
  early	
  hematoma	
  evacuaAon	
  
(<96	
  hrs)	
  vs	
  medical	
  	
  
–  Excluded	
  cerebellar	
  ICH	
  	
  
•  If	
  ICH	
  >1	
  cm	
  from	
  corAcal	
  surface,	
  OR	
  	
  
	
  	
  	
  GCS	
  <	
  8	
  
–  Surgical	
  paAents	
  tended	
  to	
  do	
  worse	
  than	
  medical	
  
•  If	
  ICH	
  <	
  1cm	
  from	
  surface	
  
–  Trended	
  toward	
  beler	
  outcomes	
  with	
  surgery,	
  but	
  not	
  
significant	
  (OR	
  0.69,	
  95%	
  CI	
  0.47-­‐1.01)	
  
Mendelow	
  AD,	
  et	
  al	
  for	
  the	
  STICH	
  InvesAgators.	
  	
  Lancet	
  2005;365(9457):387-­‐397	
  
Surgical	
  ICH	
  Trials	
  
•  Timing	
  of	
  surgery:	
  	
  What	
  is	
  “early”?	
  
– Trials	
  have	
  been	
  done	
  using	
  <24,	
  48,	
  72,	
  and	
  96	
  
hours	
  
– Regardless	
  of	
  definiAon,	
  no	
  clear	
  benefit	
  for	
  
surgery	
  
•  Minimally	
  invasive	
  techniques	
  are	
  being	
  studied	
  
Surgical	
  RecommendaAons	
  
•  For	
  most	
  paAents	
  with	
  ICH,	
  the	
  usefulness	
  of	
  surgery	
  is	
  
uncertain	
  (Class	
  IIb,	
  C)	
  
•  PaAents	
  with	
  cerebellar	
  hemorrhage	
  who	
  are	
  
deterioraAng	
  neurologically	
  or	
  who	
  have	
  brain	
  stem	
  
compression	
  and/or	
  hydrocephalus	
  from	
  ventricular	
  
obstrucAon	
  should	
  undergo	
  surgical	
  removal	
  of	
  the	
  
hemorrhage	
  as	
  soon	
  as	
  possible	
  (Class	
  I,	
  B)	
  	
  
•  IniAal	
  treatment	
  of	
  these	
  cerebellar	
  hemorrhage	
  
paAents	
  with	
  ventricular	
  drainage	
  alone	
  rather	
  than	
  
surgical	
  evacuaAon	
  is	
  not	
  recommended	
  (Class	
  	
  III,C)	
  
Surgical	
  RecommendaAons	
  
•  For	
  paAents	
  presenAng	
  with	
  lobar	
  clots	
  >30	
  cc	
  and	
  within	
  1	
  
cm	
  of	
  the	
  surface,	
  evacuaAon	
  of	
  supratentorial	
  ICH	
  by	
  
standard	
  craniotomy	
  might	
  be	
  considered	
  (Class	
  IIb,	
  B)	
  
•  The	
  effecAveness	
  of	
  minimally	
  invasive	
  clot	
  evacuaAon	
  
uAlizing	
  either	
  stereotacAc	
  or	
  endoscopic	
  aspiraAon	
  with	
  or	
  
without	
  thrombolyAc	
  usage	
  is	
  uncertain	
  and	
  is	
  considered	
  
invesAgaAonal	
  	
  (Class	
  IIb,	
  B)	
  
•  While	
  theoreAcally	
  alracAve,	
  no	
  clear	
  evidence	
  at	
  present	
  
indicates	
  that	
  ultra-­‐early	
  removal	
  of	
  supratentorial	
  ICH	
  
improves	
  funcAonal	
  outcome	
  or	
  mortality	
  rate.	
  Very	
  early	
  
craniotomy	
  may	
  be	
  harmful	
  due	
  to	
  increased	
  risk	
  of	
  
recurrent	
  bleeding	
  (Class	
  III,	
  B)	
  
Outcome	
  PredicAon	
  and	
  Withdrawal	
  
of	
  Technological	
  Support	
  
•  Aggressive	
  full	
  care	
  early	
  ager	
  ICH	
  onset	
  and	
  
postponement	
  of	
  new	
  DNR	
  orders	
  unAl	
  at	
  least	
  the	
  
second	
  full	
  day	
  of	
  hospitalizaAon	
  is	
  probably	
  
recommended	
  (Class	
  IIa,	
  B)	
  
•  PaAents	
  with	
  pre-­‐exisAng	
  DNR	
  orders	
  are	
  not	
  included	
  
in	
  this	
  recommendaAon.	
  Current	
  methods	
  of	
  
prognosAcaAon	
  in	
  individual	
  paAents	
  early	
  ager	
  ICH	
  
are	
  likely	
  biased	
  by	
  failure	
  to	
  account	
  for	
  the	
  influence	
  
of	
  withdrawal	
  of	
  support	
  and	
  early	
  DNR	
  orders.	
  	
  
PaAents	
  who	
  are	
  given	
  DNR	
  status	
  at	
  any	
  point	
  should	
  
receive	
  all	
  other	
  appropriate	
  medical	
  and	
  surgical	
  
intervenAons	
  unless	
  otherwise	
  explicitly	
  indicated.	
  
(revised	
  from	
  the	
  previous	
  guideline).	
  
Risk	
  Factors	
  for	
  Recurrent	
  ICH	
  
•  Lobar	
  ICH	
  
•  Older	
  age	
  
•  AnAcoagulaAon	
  
•  Apo	
  E	
  e2	
  or	
  e4	
  alleles	
  
•  Increased	
  number	
  of	
  “microbleeds”	
  on	
  MRI	
  
Integral	
  components	
  of	
  the	
  history,	
  physical	
  examinaAon	
  &	
  	
  
work	
  up	
  of	
  the	
  ICH	
  paAent	
  in	
  the	
  emergency	
  department	
  	
  
	
  
•  History	
  	
  
•  Time	
  of	
  symptom	
  onset	
  (or	
  Ame	
  the	
  paAent	
  was	
  
last	
  normal)	
  
•  Vascular	
  risk	
  factors	
  	
  
•  MedicaAons	
  	
  
•  Recent	
  trauma	
  or	
  surgery	
  
•  DemenAa	
  
•  Alcohol	
  or	
  illicit	
  drug	
  use	
  	
  
•  Seizures	
  
•  Liver	
  disease	
  
•  Cancer	
  and	
  hematologic	
  disorders.	
  
oComments	
  
Hypertension,	
  diabetes,	
  hypercholesterolemia,	
  and	
  
smoking	
  
AnAcoagulants,	
  anAplatelet	
  agents,	
  decongestants,	
  
anAhypertensive	
  medicaAons,	
  sAmulants	
  (including	
  diet	
  
pills),	
  sympathomimeAcs	
  
CaroAd	
  endarterectomy	
  or	
  caroAd	
  stenAng	
  in	
  
parAcular,	
  as	
  ICH	
  may	
  be	
  related	
  to	
  hyperperfusion	
  
ager	
  such	
  procedures	
  
Associated	
  with	
  amyloid	
  angiopathy	
  
Cocaine	
  and	
  other	
  sympathomimeAc	
  drugs	
  are	
  
associated	
  with	
  ICH,	
  sAmulants	
  
May	
  be	
  associated	
  with	
  coagulopathy	
  
May	
  be	
  associated	
  with	
  coagulopathy	
  
 
Integral	
  components	
  of	
  the	
  history,	
  physical	
  examinaAon	
  &	
  	
  
work	
  up	
  of	
  the	
  ICH	
  paAent	
  in	
  the	
  emergency	
  department	
  	
  
•  Physical	
  Examina<on	
  
•  Vital	
  signs	
  
•  A	
  general	
  physical	
  exam	
  focusing	
  on	
  the	
  
head,	
  heart,	
  lungs,	
  abdomen,	
  and	
  
extremiAes.	
  
•  A	
  thorough	
  but	
  Ame	
  urgent	
  neurologic	
  
exam	
  	
  
Comments	
  
Fever	
  is	
  associated	
  with	
  early	
  neurologic	
  deterioraAon.
19	
  
Higher	
  iniAal	
  blood	
  pressure	
  is	
  associated	
  with	
  early	
  
neurologic	
  deterioraAon	
  and	
  increased	
  mortality.216	
  	
  
	
  
	
  
A	
  structured	
  exam	
  such	
  as	
  the	
  NaAonal	
  InsAtutes	
  of	
  
Health	
  Stroke	
  Scale	
  (NIHSS)	
  can	
  be	
  completed	
  in	
  
minutes	
  and	
  provides	
  a	
  quanAficaAon	
  that	
  allows	
  easy	
  
communicaAon	
  of	
  the	
  severity	
  of	
  the	
  event	
  to	
  other	
  
caregivers.	
  	
  Glasgow	
  Coma	
  Score	
  (GCS)	
  is	
  similarly	
  well	
  
known,	
  easily	
  computed,	
  and	
  the	
  iniAal	
  GCS	
  is	
  a	
  strong	
  
predictor	
  of	
  long	
  term	
  outcome.	
  	
  167,	
  215	
  These	
  can	
  be	
  
supplemented	
  as	
  needed.	
  
 
Integral	
  components	
  of	
  the	
  history,	
  physical	
  examinaAon	
  &	
  	
  
work	
  up	
  of	
  the	
  ICH	
  paAent	
  in	
  the	
  emergency	
  department	
  
	
  	
  •  Serum	
  and	
  Urine	
  Tests	
  
•  Complete	
  blood	
  count,	
  electrolytes,	
  blood	
  urea	
  
nitrogen	
  and	
  creaAnine,	
  and	
  Glucose	
  
•  Prothrombin	
  Ame	
  (PT)	
  or	
  internaAonal	
  
normalized	
  raAo	
  (INR)	
  and	
  an	
  acAvated	
  parAal	
  
thromboplasAn	
  Ame	
  (aPTT)	
  
•  Toxicology	
  screen	
  in	
  young	
  or	
  middle-­‐aged	
  
paAents	
  to	
  detect	
  cocaine	
  and	
  other	
  
sympathomimeAc	
  drugs	
  of	
  abuse	
  
•  Urinalysis	
  and	
  urine	
  culture	
  and	
  a	
  pregnancy	
  
test	
  in	
  a	
  woman	
  of	
  childbearing	
  age.	
  	
  
Higher	
  creaAnine	
  is	
  associated	
  with	
  hematoma	
  
expansion.	
  Higher	
  serum	
  glucose	
  is	
  associated	
  
with	
  hematoma	
  expansion	
  and	
  worse	
  outcome	
  
(although	
  there	
  are	
  no	
  data	
  to	
  suggest	
  that	
  
normalizaAon	
  improves	
  outcome).216,	
  217	
  	
  
Warfarin-­‐related	
  hemorrhages	
  are	
  associated	
  
with	
  an	
  increased	
  hematoma	
  volume,	
  greater	
  risk	
  
of	
  expansion,	
  and	
  increased	
  morbidity	
  and	
  
mortality.	
  17,	
  197,	
  218	
  	
  
Cocaine	
  and	
  other	
  sympathomimeAc	
  drugs	
  are	
  
associated	
  with	
  ICH	
  
 
Integral	
  components	
  of	
  the	
  history,	
  physical	
  examinaAon	
  &	
  	
  
work	
  up	
  of	
  the	
  ICH	
  paAent	
  in	
  the	
  emergency	
  department	
  	
  
	
  •  Other	
  Rou<ne	
  Tests	
  
•  EKG	
  
•  Chest	
  radiograph	
  
•  Neuroimaging	
  
To	
  assess	
  for	
  acAve	
  coronary	
  ischemia	
  or	
  
prior	
  cardiac	
  injury	
  that	
  may	
  indicate	
  poor	
  
cardiac	
  funcAon,	
  and	
  to	
  obtain	
  a	
  baseline	
  in	
  
the	
  event	
  of	
  cardiopulmonary	
  issues	
  during	
  
hospitalizaAon.	
  
	
  
	
  
As	
  described	
  in	
  the	
  text	
  

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GEMC: Intracerebral Hemorrhage (ICH): Resident Training

  • 1. Project: Ghana Emergency Medicine Collaborative Document Title: Intracerebral Hemorrhage (ICH) Author(s): William Barsan, MD License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution Share Alike-3.0 License: http://creativecommons.org/licenses/by-sa/3.0/ We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, and adapt it. These lectures have been modified in the process of making a publicly shareable version. The citation key on the following slide provides information about how you may share and adapt this material. Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions, corrections, or clarification regarding the use of content. For more information about how to cite these materials visit http://open.umich.edu/privacy-and-terms-use. Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about your medical condition. Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers. 1
  • 2. Attribution Key for more information see: http://open.umich.edu/wiki/AttributionPolicy Use + Share + Adapt Make Your Own Assessment Creative Commons – Attribution License Creative Commons – Attribution Share Alike License Creative Commons – Attribution Noncommercial License Creative Commons – Attribution Noncommercial Share Alike License GNU – Free Documentation License Creative Commons – Zero Waiver Public Domain – Ineligible: Works that are ineligible for copyright protection in the U.S. (17 USC § 102(b)) *laws in your jurisdiction may differ Public Domain – Expired: Works that are no longer protected due to an expired copyright term. Public Domain – Government: Works that are produced by the U.S. Government. (17 USC § 105) Public Domain – Self Dedicated: Works that a copyright holder has dedicated to the public domain. Fair Use: Use of works that is determined to be Fair consistent with the U.S. Copyright Act. (17 USC § 107) *laws in your jurisdiction may differ Our determination DOES NOT mean that all uses of this 3rd-party content are Fair Uses and we DO NOT guarantee that your use of the content is Fair. To use this content you should do your own independent analysis to determine whether or not your use will be Fair. { Content the copyright holder, author, or law permits you to use, share and adapt. } { Content Open.Michigan believes can be used, shared, and adapted because it is ineligible for copyright. } { Content Open.Michigan has used under a Fair Use determination. } 2
  • 3. Intracerebral  Hemorrhage  (ICH)   William  Barsan,  MD   Department  of  Emergency  Medicine   Delldot,  Wikimedia  Commons  
  • 4. IntroducAon   •  Spontaneous  (atraumaAc)  ICH:  bleeding  into   the  parenchyma  of  the  brain  that  may  extend   into  the  ventricles  and  subarachnoid  space.   •  10-­‐15%  of  all  cases  of  stroke     •  Mortality   – 6  month        30-­‐50%   – One  year      50%  
  • 5. Intracerebral  Hemorrhage   •  Spontaneous,  non-­‐traumaAc  intracerebral  hemorrhage   (ICH)    is  a  significant  cause  of  morbidity  and  mortality   throughout  the  world.   •   Excellent  medical  care  has  a  potent,  direct  impact  on   ICH      morbidity  and  mortality,  even  before  a  specific   therapy  is  found.       •  The  overall  aggressiveness  of  ICH  care  is  directly   related  to  mortality  from  this  disease.     •  AHA  has  new  guidelines  for  2010,  updated  from  2007  
  • 6. ClassificaAon   •  Primary  (80-­‐90%)   – Spontaneous  rupture  of  small  vessels  damaged  by   chronic  hypertension  or  amyloid  angiopathy   •  Secondary   – Vascular  abnormaliAes  (AVM,  aneurysm)   – Tumor   – Coagulopathy  
  • 7. Pathophysiological  features   •  Origin  of  hematoma   – DegeneraAve  changes  in  the  vessel  wall  induced   by  chronic  hypertension.   – DilataAon  in  the  walls  of  small  arterioles.   (microaneurysms)   – Electron-­‐microscopical  study:  most  bleeding  occur   at  the  bifurcaAon  of  affected  arteries.  
  • 8. Where  do  they  occur?   A.  Lobar       B.  Basal  ganglia     C.  Thalamus     D.  Brain  stem  (pons   predominantly)     E.  Cerebellum   A B C   D E   Looie496,  Wikimedia  Commons  
  • 9. Predictors  of  Outcome   •  Hematoma  volume   •  GCS   •  Intraventricular  hemorrhage   •  Age   •  ICH  locaAon   •  Increased  cerebral  edema   Source  Undetermined   Source  Undetermined  
  • 10. Mechanisms  of  Injury   •  Early  hematoma  growth              –  Hematoma  enlargement              –  Increase  in  ICP,  Assue  disrupAon,  shear    forces   •  Edema  and  toxic  effects  of  blood  products              –  OsmoAcally  acAve  serum  products                –  Thrombin   •  Inflammatory  response  
  • 11. Hematoma  Expansion   72%  have  some  hematoma   expansion  over  the  first  24  hours       38%  have  significant  (>33%)   expansion  over  24  hours       In  26%  of  these  cases,  the   enlargement  is  within  1  hour   Delldot,  Wikimedia  Commons  
  • 12. DefiniAon  of  Classes  and  Levels  of  Evidence  Used  in   AHA  Stroke  Council  RecommendaAons   •  Class  I      Condi<ons  for  which  there  is  evidence  for  and/or  general                                                                agreement  that  the  procedure  or  treatment  is  useful  and  effec<ve.   •  Class  II      Condi<ons  for  which  there  is  conflic<ng  evidence  and/or  a                                                                  divergence  of  opinion  about  the  usefulness/efficacy  of  a  procedure  or  treatment.   •         Class  IIa    The  weight  of  evidence  or  opinion  is  in  favor  of  the  procedure  or                treatment.   •      •        Class  IIb  Usefulness/efficacy  is  less  well  established  by              evidence  or  opinion.   •   Class  III      Condi<ons  for  which  there  is  evidence  and/or  general  agreement                                                                that  the  procedure  or  treatment  is  not  useful/effec<ve  and  in  some  cases  may  be  harmful.   •  Therapeu<c  recommenda<ons   •   Level  of  Evidence  A      Data  derived  from  mulAple  randomized  clinical  trials  or                                                                  metaanalyses   •   Level  of  Evidence  B      Data  derived  from  a  single  randomized  trial  or                                                                    nonrandomized  studies   •   Level  of  Evidence  C      Consensus  opinion  of  experts,  case  studies,  or  standard  of    care   •     Diagnos<c  recommenda<ons   •   Level  of  Evidence  A      Data  derived  from  mulAple  prospecAve  cohort  studies                                                                  using  a  reference  standard  applied  by  a  masked  evaluator   •   Level  of  Evidence  B      Data  derived  from  a  single  grade  A  study,  or  one  or  more                                                                case-­‐control  studies,  or  studies  using  a  reference  standard                                                                  applied  by  an  unmasked  evaluator   •   Level  of  Evidence  C      Consensus  opinion  of  experts  
  • 13. PresentaAon  Content  Areas   •   Neuroimaging  of  ICH   •     Hemostasis   •     Blood  pressure  management     •     InpaAent  management  and  prevenAon  of  secondary  injury   •     Intracranial  pressure    (ICP)/glucose/seizures/ hydrocephalus       •     Surgical  treatment  of  ICH       •     Intraventricular  hemorrhage     •     Withdrawal  of  technological  support   •     PrevenAon  of  recurrent  ICH   •     RehabilitaAon  and  recovery  
  • 14. Neuroimaging  of  ICH     Computed  tomography  (CT)   scan  showing  Leg   hemisphere  intracerebral   hemorrhage  (ICH)  with   intraventricular     extravasaAon   Large  leg  intraparenchymal  hematoma  (ICH)   Source  Undetermined  
  • 15. RecommendaAons  for  Neuroimaging   in  ICH   •  Rapid  neuroimaging  with  CT  or  MRI  is   recommended  to  dis<nguish  ischemic   stroke  from  ICH     •  CT  angiography  and  contrast-­‐enhanced  CT   may  be  considered  to  help  iden<fy   pa<ents  at  risk  for  hematoma  expansion     •  CT  angiography,  CT  venography,  contrast-­‐ enhanced  CT,  contrast-­‐enhanced  MRI,   MRA  and  MRV  can  be  useful  to  evaluate   for  underlying  structural  lesions  including   vascular  malforma<ons  and  tumors  when   there  is  clinical  or  radiologic  suspicion     Class  I,  Level  of   Evidence  A  (Unchanged   from  the  previous   guideline).       Class  IIb,  Level  of   Evidence  B       Class  IIa,  Level  of   Evidence  B  (New   recommenda:on).        
  • 16.   CTA  and  ICH:   SPOT  sign   •  CT  contrast  extravasates  into   hematoma   –  Spot  sign,  white  arrows   •  May  predict  hematoma   expansion   Source  Undetermined  
  • 17. Imaging  of  Underlying  Structural   Lesions?   •  CTA/CTV,  MRI  with  gadolinium,  MRA/MRV  can  all  be  useful  to   evaluate  for  underlying  structural  lesions,  including  vascular   malformaAons  and/or  tumors   –  When  there  is  clinical  or  radiologic  suspicion  
  • 18. AnAcoagulaAon  and  ICH   AnAcoagulaAon  leads  to  more   hematoma  growth  and  higher   mortality   Reverse  warfarin  promptly  and   aggressively   FFP  or  prothrombin  complex   concentrates  (PCCs)   IV  vitamin  K   Faster  than  SQ/PO  but  a  small   risk  of  anaphylactoid  reacAon   Source  Undetermined  
  • 19.   Reversal  of  AnAcoagulaAon  in  ICH  paAents   •  PaAents  with  a  severe  coagulaAon  factor  deficiency  or  severe   thrombocytopenia  should  receive  appropriate  factor  replacement   therapy  or  platelets,  respecAvely    (Class  I,  C)   •  PaAents  with  ICH  whose  INR  is  elevated  due  to  OAC’s  should  have   their  warfarin  withheld,  receive  therapy  to  replace  vitamin  K-­‐ dependent  factors  and  correct  the  INR,  and  receive  intravenous   vitamin  K    (Class  I,  C)   •  PCCs  have  not  shown  improved  outcome  compared  with  FFP  but  may   have  fewer  complicaAons  compared  with  FFP  and  are  reasonable  to   consider  as  an  alternaAve  to  FFP  (Class  IIa,  B)   •  The  usefulness  of  platelet  transfusions  in  ICH  paAents  with  a  history  of   anAplatelet  use  is  unclear  and  is  considered  invesAgaAonal  (Class    IIb,   B)  
  • 20.   PotenAal  Treatments  for  ICH:   The  Problem  of  Hematoma  Expansion   Source  Undetermined  
  • 21. Hematoma  Expansion  is  Common   •  Brol,  et  al.,  1997   –  103  pts.,  prospecAve  observaAonal  study  with  serial  CT   scanning  (baseline,  1  hr  and  20  hrs  following  ICH)   –  26%  showed  >33%  enlargement  on  1  hr  CT   –  38%  showed  >33%  enlargement  on  20  hr  CT   –  Neurologic  deterioraAon  correlated  with  hematoma   expansion   •  Brol  T  et  al,  Stroke.  1997  Jan;28(1):1-­‐5.  
  • 22. Recombinant  AcAvated  Factor  VII*   •  rFVIIa,  NovoSeven©   •  Used  for  hemophilia   •  Induces  local  hemostasis  when  it   binds  to  Assue  factor   –  The  complex  can  acAvate  Factors  IX  and   X   –  Factor  Xa  helps  convert  prothrombin  to   thrombin    *Not  FDA  approved  for  ICH   Harmid,  Wikimedia  Commons  
  • 23. “FAST”  Trials   •  A  phase  II  randomized  trial  showed  that  treatment  with  rFVIIa  within  four   hours  ager  ICH  onset     –  limited  hematoma  growth     –  improved  clinical  outcomes  relaAve  to  placebo     –  increased  frequency  of  thromboembolic  events  (7%  vs.  2%)   •  A  subsequent  phase  III  study  comparing  placebo  to  20  μg/kg  and  80  μg/kg   of  rFVIIa:     –  both  doses  diminished  hematoma  enlargement   –  failed  to  show  differences  in  clinical  outcome   –  Overall  serious  thromboembolic  adverse  event  rates  were  similar,  the  higher  rFVIIa  (80   μg/kg)  group  had  significantly  more  arterial  events  than  placebo.       •  The  authors  noted  imbalances  in  treatment  groups,  parAcularly  intraventricular   hemorrhage  in  the  higher  dose  rFVIIa  group   Mayer  SA,  et  al  for  the  FAST  Trial  InvesAgators.,  N  Engl  J  Med.  2008  May  15;358(20):2127-­‐37.   Mayer  SA  for  the  FAST  Trial  InvesAgators.    N  Engl  J  Med.  2005  Feb  24;352(8):777-­‐85.  
  • 24. Factor  VIIa   •  Factor  VIIa  can  limit  hematoma  expansion  in  non-­‐ coagulopathic  paAents,  but  also  increases  thromboembolic   risk.   –  rFVIIa  is  not  recommended  in  unselected  pa:ents   •  rFVIIa  does  NOT  replace  clovng  factors,  even  though  INR   normalizes   –  rFVIIa  is  not  recommended  as  the  only  agent  to  reverse   INR  in  ICH  pa:ents   Mayer  SA,  et  al  for  the  FAST  Trial  InvesAgators.,  N  Engl  J  Med.  2008  May  15;358(20):2127-­‐37.   Mayer  SA  for  the  FAST  Trial  InvesAgators.    N  Engl  J  Med.  2005  Feb  24;352(8):777-­‐85.  
  • 25. Blood  Pressure  and  ICH:     Is  it  safe  to  lower  BP  in  the  acute   sevng?   Saperaud,  Wikimedia  Commons  
  • 26.   INTERACT     •  404  ICH  pts,  randomized  into:   – Target  SBP  of  140mmHg  within  1  hr  OR   – Target  SBP  of  180mmHg     •  Trend  towards  lower  hematoma  growth   •  No  increase  in  adverse  events  related  to  BP-­‐lowering   •  No  differences  in  clinical  outcome/QOL   – Not  powered  for  clinical  endpoints   Anderson  CS,  et  al.  Lancet  Neurol.  2008;7(5):391-­‐399  
  • 27. ATACH   •  80  ICH  pts   •  4-­‐Aer,  dose  escalaAon  of  IV  nicardipine-­‐based   lowering  of  BP   •  Confirmed  safety  and  feasibility  of  early  rapid   BP  lowering   Qureshi  AI,  et  al,    for  the  ATACH  InvesAgators  Arch  Neurol.  2010  May;67(5):570-­‐6  
  • 28. Summary  of  New  BP  Lowering  in   ICH  Trials   •  These  new  studies  have  shown  that  intensive   BP  lowering  is  clinically  feasible  and   potenAally  safe   •  BP  targets,  duraAon  of  therapy  is  unknown   •  No  studies  have  shown  clinical  benefit  so  far  
  • 29.   Blood  Pressure  RecommendaAons   •  UnAl  ongoing  clinical  trials  of  BP  intervenAon   for  ICH  are  completed,  physicians  must   manage  BP  on  the  basis  of  the  present   incomplete  efficacy  evidence  (Class  IIb,  C)   •  In  paAents  presenAng  with  a  systolic  BP  of   150-­‐220  mmHg,  acute  lowering  of  systolic  BP   to  140  mmHg  is  probably  safe  (Class  IIa,  B)  
  • 30. Recommended  BP  Treatment  Targets   •  If  SBP  is  >200  mmHg  or  MAP  is  >150  mm  Hg,  then   consider  aggressive  reducAon  of  blood  pressure  with   conAnuous  intravenous  infusion,  with  frequent  blood   pressure  monitoring  every  5  minutes.     •  If  SBP  is  >180  mmHg  or  MAP  is  >130  mm  Hg  and  there   is  the  possibility  of  elevated  ICP,  then  consider   monitoring  ICP  and  reducing  blood  pressure  using   intermilent  or  conAnuous  intravenous  medicaAons   while  maintaining  a  cerebral  perfusion  pressure  >  60   mmHg  
  • 31. Recommended  BP  Treatment  Targets     •  If  SBP  is  >180  mmHg  or  MAP  is  >130  mm  Hg   and  there  is  not  evidence  of  elevated  ICP,   then  consider  a  modest  reducAon  of  blood   pressure  (eg,  MAP  of  110  mm  Hg  or  target   blood  pressure  of  160/90  mm  Hg)  using   intermilent  or  conAnuous  intravenous   medicaAons  to  control  blood  pressure,  and   clinically  reexamine  the  paAent  every  15   minutes.  
  • 32. InpaAent  Management:  Medical   ConsideraAons   •  IniAal  monitoring  and  management  of  ICH  paAents  should   take  place  in  an  intensive  care  unit  with  physician  and   nursing  neuroscience  intensive  care  experAse    (Class  I,  B)   •  Glucose  should  be  monitored  and  normoglycemia  is   recommended    (Class  I,  C)   •  PaAents  with  ICH  should  have  intermilent  pneumaAc   compression  for  prevenAon  of  venous  thromboembolism  in   addiAon  to  elasAc  stockings  (Class  I,  B)   •  Ager  documentaAon  of  cessaAon  of  bleeding,  low-­‐dose   subcutaneous  low-­‐molecular-­‐weight  heparin  or   unfracAonated  heparin  may  be  considered  for  prevenAon   of  venous  thromboembolism  in  paAents  with  lack  of   mobility  ager  1  to  4  days  from  onset    (Class  IIb,  B)  
  • 33.   InpaAent  Management  of  PrevenAon  of   Secondary  Brain  Injury:  Medical  ConsideraAons   Seizures  and  An:epilep:c  Drugs   •  Clinical  seizures  should  be  treated  with  anA-­‐epilepAc   drugs  (Class  I,  A)   •  ConAnuous  EEG  monitoring  is  probably  indicated  in   ICH  paAents  with  depressed  mental  status  out  of   proporAon  to  the  degree  of  brain  injury  (Class  II,  B)   •  PaAents  with  a  change  in  mental  status  who  are  found   to  have  electrographic  seizures  on  EEG  should  be   treated  with  anA-­‐epilepAc  drugs  (Class  I,  C)   •  ProphylacAc  anAconvulsant  medicaAon  should  not  be   used  (Class  III,  B)  
  • 34. Hydrocephalus   •  Hydrocephalus  can   accompany  ICH,  especially   intravenAcular  rupture            (IVH)   •  Elevates  ICP   •  Results  in  early  or  delayed   neurologic  deterioraAon   Source  Undetermined  
  • 35. Intracranial  Pressure  Treatment   Algorithm     Source  Undetermined  
  • 36. CLEAR-­‐IVH  Trial   •  52  pts  with  IVH   •  Open-­‐label    intra-­‐ventricular  rt-­‐PA  to  accelerate   blood  clearance  and  lysis   •  Adverse  events   –  SymptomaAc  bleeding  4%   –  Bacterial  ventriculiAs  2%   –  30  day  mortality  17%   •  Efficacy  requires  confirmaAon  before  use  of   intraventricular  fibrinolysis  can  be   recommended,  Phase  III  trial  in  progress  
  • 37. ICP  Monitoring  and  Ventriculostomy   •  PaAents  with  a  GCS  score  of  8  or  less,  those  with  clinical   evidence  of  transtentorial  herniaAon,  or  those  with   significant  IVH  or  hydrocephalus  might  be  considered  for   ICP  monitoring  and  treatment.  A  CPP  of  50-­‐70  mmHg  may   be  reasonable  to  maintain  depending  on  the  status  of   cerebral  autoregulaAon    (Class  IIb,  C)   •  Ventricular  drainage  as  treatment  for  hydrocephalus  is   reasonable  in  paAents  with  decreased  level  of   consciousness  (Class  IIa,  B)   •  Although  intraventricular  administraAon  of  rt-­‐PA  in  IVH   appears  to  have  a  fairly  low  complicaAon  rate,  efficacy  and   safety  of  this  treatment  is  uncertain  and  is  considered   invesAgaAonal  (Class  IIb,  B)  
  • 39. STICH  Trial   •  902  ICH  pts  randomized  trial  of  early  hematoma  evacuaAon   (<96  hrs)  vs  medical     –  Excluded  cerebellar  ICH     •  If  ICH  >1  cm  from  corAcal  surface,  OR          GCS  <  8   –  Surgical  paAents  tended  to  do  worse  than  medical   •  If  ICH  <  1cm  from  surface   –  Trended  toward  beler  outcomes  with  surgery,  but  not   significant  (OR  0.69,  95%  CI  0.47-­‐1.01)   Mendelow  AD,  et  al  for  the  STICH  InvesAgators.    Lancet  2005;365(9457):387-­‐397  
  • 40. Surgical  ICH  Trials   •  Timing  of  surgery:    What  is  “early”?   – Trials  have  been  done  using  <24,  48,  72,  and  96   hours   – Regardless  of  definiAon,  no  clear  benefit  for   surgery   •  Minimally  invasive  techniques  are  being  studied  
  • 41. Surgical  RecommendaAons   •  For  most  paAents  with  ICH,  the  usefulness  of  surgery  is   uncertain  (Class  IIb,  C)   •  PaAents  with  cerebellar  hemorrhage  who  are   deterioraAng  neurologically  or  who  have  brain  stem   compression  and/or  hydrocephalus  from  ventricular   obstrucAon  should  undergo  surgical  removal  of  the   hemorrhage  as  soon  as  possible  (Class  I,  B)     •  IniAal  treatment  of  these  cerebellar  hemorrhage   paAents  with  ventricular  drainage  alone  rather  than   surgical  evacuaAon  is  not  recommended  (Class    III,C)  
  • 42. Surgical  RecommendaAons   •  For  paAents  presenAng  with  lobar  clots  >30  cc  and  within  1   cm  of  the  surface,  evacuaAon  of  supratentorial  ICH  by   standard  craniotomy  might  be  considered  (Class  IIb,  B)   •  The  effecAveness  of  minimally  invasive  clot  evacuaAon   uAlizing  either  stereotacAc  or  endoscopic  aspiraAon  with  or   without  thrombolyAc  usage  is  uncertain  and  is  considered   invesAgaAonal    (Class  IIb,  B)   •  While  theoreAcally  alracAve,  no  clear  evidence  at  present   indicates  that  ultra-­‐early  removal  of  supratentorial  ICH   improves  funcAonal  outcome  or  mortality  rate.  Very  early   craniotomy  may  be  harmful  due  to  increased  risk  of   recurrent  bleeding  (Class  III,  B)  
  • 43. Outcome  PredicAon  and  Withdrawal   of  Technological  Support   •  Aggressive  full  care  early  ager  ICH  onset  and   postponement  of  new  DNR  orders  unAl  at  least  the   second  full  day  of  hospitalizaAon  is  probably   recommended  (Class  IIa,  B)   •  PaAents  with  pre-­‐exisAng  DNR  orders  are  not  included   in  this  recommendaAon.  Current  methods  of   prognosAcaAon  in  individual  paAents  early  ager  ICH   are  likely  biased  by  failure  to  account  for  the  influence   of  withdrawal  of  support  and  early  DNR  orders.     PaAents  who  are  given  DNR  status  at  any  point  should   receive  all  other  appropriate  medical  and  surgical   intervenAons  unless  otherwise  explicitly  indicated.   (revised  from  the  previous  guideline).  
  • 44. Risk  Factors  for  Recurrent  ICH   •  Lobar  ICH   •  Older  age   •  AnAcoagulaAon   •  Apo  E  e2  or  e4  alleles   •  Increased  number  of  “microbleeds”  on  MRI  
  • 45. Integral  components  of  the  history,  physical  examinaAon  &     work  up  of  the  ICH  paAent  in  the  emergency  department       •  History     •  Time  of  symptom  onset  (or  Ame  the  paAent  was   last  normal)   •  Vascular  risk  factors     •  MedicaAons     •  Recent  trauma  or  surgery   •  DemenAa   •  Alcohol  or  illicit  drug  use     •  Seizures   •  Liver  disease   •  Cancer  and  hematologic  disorders.   oComments   Hypertension,  diabetes,  hypercholesterolemia,  and   smoking   AnAcoagulants,  anAplatelet  agents,  decongestants,   anAhypertensive  medicaAons,  sAmulants  (including  diet   pills),  sympathomimeAcs   CaroAd  endarterectomy  or  caroAd  stenAng  in   parAcular,  as  ICH  may  be  related  to  hyperperfusion   ager  such  procedures   Associated  with  amyloid  angiopathy   Cocaine  and  other  sympathomimeAc  drugs  are   associated  with  ICH,  sAmulants   May  be  associated  with  coagulopathy   May  be  associated  with  coagulopathy  
  • 46.   Integral  components  of  the  history,  physical  examinaAon  &     work  up  of  the  ICH  paAent  in  the  emergency  department     •  Physical  Examina<on   •  Vital  signs   •  A  general  physical  exam  focusing  on  the   head,  heart,  lungs,  abdomen,  and   extremiAes.   •  A  thorough  but  Ame  urgent  neurologic   exam     Comments   Fever  is  associated  with  early  neurologic  deterioraAon. 19   Higher  iniAal  blood  pressure  is  associated  with  early   neurologic  deterioraAon  and  increased  mortality.216         A  structured  exam  such  as  the  NaAonal  InsAtutes  of   Health  Stroke  Scale  (NIHSS)  can  be  completed  in   minutes  and  provides  a  quanAficaAon  that  allows  easy   communicaAon  of  the  severity  of  the  event  to  other   caregivers.    Glasgow  Coma  Score  (GCS)  is  similarly  well   known,  easily  computed,  and  the  iniAal  GCS  is  a  strong   predictor  of  long  term  outcome.    167,  215  These  can  be   supplemented  as  needed.  
  • 47.   Integral  components  of  the  history,  physical  examinaAon  &     work  up  of  the  ICH  paAent  in  the  emergency  department      •  Serum  and  Urine  Tests   •  Complete  blood  count,  electrolytes,  blood  urea   nitrogen  and  creaAnine,  and  Glucose   •  Prothrombin  Ame  (PT)  or  internaAonal   normalized  raAo  (INR)  and  an  acAvated  parAal   thromboplasAn  Ame  (aPTT)   •  Toxicology  screen  in  young  or  middle-­‐aged   paAents  to  detect  cocaine  and  other   sympathomimeAc  drugs  of  abuse   •  Urinalysis  and  urine  culture  and  a  pregnancy   test  in  a  woman  of  childbearing  age.     Higher  creaAnine  is  associated  with  hematoma   expansion.  Higher  serum  glucose  is  associated   with  hematoma  expansion  and  worse  outcome   (although  there  are  no  data  to  suggest  that   normalizaAon  improves  outcome).216,  217     Warfarin-­‐related  hemorrhages  are  associated   with  an  increased  hematoma  volume,  greater  risk   of  expansion,  and  increased  morbidity  and   mortality.  17,  197,  218     Cocaine  and  other  sympathomimeAc  drugs  are   associated  with  ICH  
  • 48.   Integral  components  of  the  history,  physical  examinaAon  &     work  up  of  the  ICH  paAent  in  the  emergency  department      •  Other  Rou<ne  Tests   •  EKG   •  Chest  radiograph   •  Neuroimaging   To  assess  for  acAve  coronary  ischemia  or   prior  cardiac  injury  that  may  indicate  poor   cardiac  funcAon,  and  to  obtain  a  baseline  in   the  event  of  cardiopulmonary  issues  during   hospitalizaAon.       As  described  in  the  text