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Intracerebral Hemorrhage Contemporary Management
J. Teitlelbaum, MD, FRCP(C) McGill University Université de Montréal
CCCF Toronto October 2014
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Conflicts of Interest
none
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Objectives
Be aware of new ideas beyond the guidelines Stroke. 2010;41:2108-2129
Investigation
Monitoring
Therapy
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Investigation
Guideline: Dx: non-contrast CT (MRI)
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Classification of ICH
PRIMARY (78-88%) Hypertensive
angiopathy (fibrohyalinosis)
Amyloid angiopathy
Anticoagulant Associated
SECONDARY AVM Aneurysm Cavernoma Neoplasm Coagulopathy
Alcoholic liver disease
Hemophilia Hemorrhagic infarct Toxic-cocaine
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CTA?
Guideline 2007: CTA if young, no clear cause, no HBP, signs on CT No CTA if typical age, HBP & location
Guideline 2010: Stroke. 2010;41:2108-2129
CTA if young, no clear cause, no HBP, signs on CT
More flexibility for others
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Secondary Etiology in SICH
Overall: 14 – 53% Under 50 years, no HBP, atypical location, no clear
etiology 51%
Over 50 years, HBP, typical location 2 – 4%
Pathologic study, 144 pts 36% of HBP SICH had 2nd cause
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Diagnosis of Vascular Lesions
DSA Invasive Adverse events: 0.9 & 0.5%, transient or permanent
CTA Accuracy very close to DSA High safety profile Low complication rate
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Primary SICH - Outcome
6 month prognosis dismal 40% dead within one month (half < 48H) 40% disabled and dependent 20% independent Main prognostic factor: volume
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Secondary ICH - Outcome
If SAH Mortality 33% immediate, 66% for re-bleed Rebleed: 20% first 14 days Serious morbidity 60%
If AVM (Stroke 1998) 47% intact, 3% mRS>4, Φ mortality, rebleed 7%
CVST Mortality 30-50% Good outcome: 30% Serious morbidity: 50%
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Primary ICH Factors related to outcome
GCS on presentation Age Hemorrhage location Intra-ventricular hemorrhage Blood pressure on admission Hemorrhage size (expansion)
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Early growth occurs in all locations
Brott (1997) N=103
Kazui (1994) N=186
Fujii (1996) N=359
Initial CT time 0-3 hrs 0-24 hrs 0-24 hrs Putamen 34% 16% 19% Thalamus 50% 21% 10% Lobar 32% 29% 6% Cerebellar 0% 25% 12% Pons 40% 40% 28% Other 43% 25% 13% TOTAL 38% 22% 14%
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Size is the most important predictor of patient outcome
DEAD FULL RECOVERY
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Predicting ICH expansion
Time since onset
Spot sign
Blood pressure
Shape of the hematoma
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CTA - Spot Sign
Extraluminal extravasation of contrast Serpiginous or spot-like, single or multiple,
within the hematoma, no external vessel connection
Seen in 20-30% within 3H of ictus Marker of hematoma expansion
(OR 3.1, p
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CTA Source Images: Additional Data
Spot Sign
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So…
ICH location alone cannot R/O a vascular lesion
All lesions do not have the same outcomes Primary SICH outcome related to ICH growth Etiology & Spot Sign: CTA
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Investigation Follow the Guideline?
Not this part of the guideline CTA for all SICH
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SICH - Monitoring
Traditional (guideline): Clinical exam SBP/MAP ICP / CPP Repeat CT @ 24H
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SICH – Multi-modality Monitoring
Beyond the guideline (?? Useful) cEEG Non-invasive Brain O2 Intracranial monitoring:
PbtO2 (Licox) Microdialysis:
lactate/pyruvate/glutamate/glycerol/glucose
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cEEG Useful?
Sz in 31% (lobar, cortical, ICH growth) NCS in 10% - 30% 85-94% of Sz detected ≤ 48 hours of cEEG
initiation (56% in first hour)
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cEEG Useful?
Seizures & PEDs associated with Neurologic worsening (NIHSS) in midline shift (p < 0.03) poor outcome
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cEEG Useful?
Seizure prophylaxis Messé SR, Neurocrit Care 2009, (CHANT) DPH vs none, 10d, clear in cognition
Taylor, Neurocrit Care 2011 Keppra vs DPH Better outcome, less Sz, better cognition
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So… cEEG
Find the seizures that matter Treat Sz, and ? PEDs Avoid prophylaxis
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Brain Tissue Oxygenation
Jugular venous bulb oxymetry Direct PbtO2 Near infrared spectroscopy Oxygen-15 PET
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Brain Tissue Oxygenation
Licox intracranial PbtO2 T° dependent Samples 15 mm of tissue Usual indications
Diffuse injury Focal injury (SDH, contusion) SAH Infarction
2
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Brain Tissue Oxygenation
Near Infrared Spectroscopy (NIRS)
Reflectance mode Contribution of extracranial tissue Real time Δ regional SO2 Useful for general changes Several aspects need refinement
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So… Get with the Guidelines or Go Beyond
cEEG Will do this if possible, 48-72 hours
Near Infra Red Spectroscopy (NIRS) Coming soon (when the kinks are ironed out)
Intracranial monitoring: Not for prime time
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SICH Treatment
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Treatment Modalities
General supportive care Treatment of ICHT Hematoma resection Management of intra-ventricular hemorrhage
Seizure prophylaxis / treatment Prevention of hematoma growth BP management
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Seizure prophylaxis / Treatment
Do Seizures and ECS occur with ICH? Yes (2.7-17% clinical, 28-31% cEEG)
Do they affect outcome? No (population based, clinical Sz) Yes (newer, cEEG based studies)
Does prophylaxis Sz yes
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Seizure prophylaxis / Treatment
Does prophylaxis improve outcome? No: DPH Yes: Keppra
Does Sz therapy improve outcome? Yes: clinical seizures Yes: EEG Sz with Δ in LOC ?: EEG PLEDS or Sz without Δ in LOC
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Seizure prophylaxis
Guideline: No
Beyond the guideline No, if cEEG available Yes if unexplained LOC, first 48H cortical ICH Keppra (if can load)
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Seizure Treatment
Guideline Treat clinical Sz Treat EEG Sz if unexplained or Δ in LOC Consider cEEG
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Blood Pressure Management
Does BP affect prognosis? Can BP be lowered safely? Does this ICH growth? Does this affect outcome?
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Prognosis and Acute Blood Pressure 1
mon
th m
orta
lity
(%)
MAP (mm Hg)
Fogelhom et al, Stroke, 28: 1396-400, 1997 Okumura et al, J. Hypertension, 23: 1217-23, 2005
↑ Early Neurological Deterioration ↓ Functional Outcome (90 days)
1 m
onth
mor
talit
y (%
)
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Prognosis and Acute Blood Pressure: ICH
n=1097
Fogelhom et al, Stroke, 28: 1396-400, 1997 Okumura et al, J. Hypertension, 23: 1217-23, 2005
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Blood Pressure and Hematoma Evolution
Target max SBP
No Enlargement
Hematoma Enlargement
140 mmHg 16 2 9% p=0.025 150 mmHg 14 1
160 mmHg 22 8 30%
170 mmHg 8 5
Ohwaki et al, Stroke, 35: 1353-1367, 2004 Retrospective, 170 Pts
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BP & Outcome
Neurology Meta-analysis 2014 ADAPT (
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BP & Outcome
Neurology 2014 meta-analysis,
Syst to 140 mm Hg in ≤ 1H vs ≥ 180 syst
Death or dependency (3 months)
Greater in ICH growth
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BP & Outcome
Tanaka et al Stroke 2014: BP variability worsens outcome (mRS) No effect of ICH growth
Kobayashi et al Stroke 2014: continuous 24H control ≤ 120-160 mmHg syst Improves outcome (mRS) No effect on ICH growth
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BP & Outcome
NEJM 2013: No Δ in D&D, mRS increment
No Δ ICH growth
PLOS one May 22, 2014 New meta-analysis
No Δ in D&D, mRS increment
No Δ ICH growth
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So…
Aggressive By 6H post event ≤ 1H of arrival Very little effect on ICH growth Better outcome ?? Statistical effect??
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Lower BP Follow the guideline?
If SBP ≥180 mm Hg or MAP is 130 mm Hg If no ICP, consider MAP ≤110 mm Hg or
BP of 160/90 mm Hg) Re-examine the patient every 15 min. SBP to 140 mm Hg is safe
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Or… Be ahead of the curve
Aggressive (< 4-6H of event) Fast (
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Prognosis and Acute Blood Pressure: ICH
n=1097
Fogelhom et al, Stroke, 28: 1396-400, 1997 Okumura et al, J. Hypertension, 23: 1217-23, 2005
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2.0 hours after onset 6.5 hours after onset
Prevent Early Hematoma Growth
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Prevent ICH Growth
By BP ??
By rFVIIa
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-20
-15
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-5
0
5
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P l a c e b o 4 0 u g /k g rF V I Ia 8 0 u g /k g rF V I Ia 1 6 0 u g /k g rF V I Ia-20
-15
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0
5
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25
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Percent Change in ICH Volume at 24 Hours
Boxes depict 98.3%
confidence intervals
29%
11% 14%
52% RR
16%
45% RR 62% RR
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Modified Rankin Scale at Day 90
0% 20% 40% 60% 80% 100%
160 µg/kg
80 µg/kg
40 µg/kg
Placebo
mRS 6 mRS 4-5 mRS 2-3 mRS 0-1
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Onset-CT interval (h)
Prospective Retrospective
Brott Fujii Kazui Takizawa
0-3 38% 18% 36% 17%
3-6 N/A 8% 16% 6%
6-24 N/A 2% 10% 0%
Hematoma Evolution and rFVIIa
rFVIIa within 4 hours: Dose dependent attenuation of hematoma expansion No effect on mRS at 90 days
↓3.3ml ↓4.5ml ↓5.8ml
Mayer et al. NEJM 2005; 352: 777-85
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Spot Sign Negative
CTA Based rFVIIa Selection Trials The SpoT sign fOr Predicting and treating ICH growTh study: STOP-IT SPOTRIAS/NINDS PI: M. Flaherty
‘SPOT sign’ seLection of Intracerebral hemorrhage to Guide Hemostatic Therapy: SPOTLIGHT CSN/ CIHR PI: D. Gladstone
CTA
Acute ICH < 6 hours
Spot Sign Positive
rFVIIa Placebo
NCCT at 24 hours
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ICH Summary
Poor prognosis Hematoma expands early (≤4h) ICH Expansion can be predicted HBP is a likely factor in prognosis Seizures occur early & may affect outcome
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ICH Summary Beyond the Guidelines
Investigation: CTA on all patients
Monitoring: Add cEEG for 48H PbtO2: not yet NIRS: coming soon
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ICH Summary Beyond the Guidelines
Seizure prophylaxis: No, or Keppra x 48H BP therapy Aggressive (1H) to ≤ 140 mm Hg: not yet Aggressive (1H) to ≤ 160 mm Hg: OK
Activated fVII: Will know soon
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References
Claassen J. Neurology. 2007 Sep 25;69(13):1356-65 Vesp PM. Neurology. 2003 May 13;60(9):1441-6. Vespa PM. J Clin Neurophysiol. 2005 Apr;22(2):99-106 Messé SR. Neurocrit Care. 2009;11(1):38-44. Jensen MB. Neurol Res. 2013 Nov;35(9):984-7 Gilmore E. Neurologist. 2010 May;16(3):165-75 Pasero S. Epilepsia. 2002 Oct;43(10):1175-80 Ohwaki K. Stroke. 2004 Jun;35(6):1364-7. Barber PA. Int J Stroke. 2014 Jan;9(1):59-60
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References
Tanaka E. Stroke. 2014 Aug;45(8):2275-9. Kobayashi J. Stroke. 2014 Mar;45(3):868-70 Taylor S. Neurocrit Care. 2011 Aug;15(1):80-4 Gould B. Stroke 2013;44:1726-1728 McCourt R Stroke. 2014 May;45(5):1292-8 Hongxuan W PLOS One 2014;9(5):e97917 Anderson CS. Lancet Neurol. 2008;7(5):391-9 Khosravani H. AJNR 2013;34(8):1481-7
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Slide Number 1Conflicts of InterestObjectivesInvestigation�Classification of ICHCTA?�Secondary Etiology in SICHDiagnosis of Vascular LesionsPrimary SICH - OutcomeSecondary ICH - OutcomePrimary ICH�Factors related to outcomeEarly growth occurs in all locationsSize is the most important predictor of patient outcomePredicting ICH expansionCTA - Spot SignCTA Source Images: Additional DataSo…Investigation�Follow the Guideline?SICH - MonitoringSICH – Multi-modality MonitoringcEEG Useful?cEEG Useful?cEEG Useful?So… cEEGBrain Tissue OxygenationBrain Tissue OxygenationBrain Tissue OxygenationSo… Get with the Guidelines �or Go BeyondSICH TreatmentTreatment ModalitiesSeizure prophylaxis / TreatmentSeizure prophylaxis / TreatmentSeizure prophylaxisSeizure TreatmentBlood Pressure ManagementPrognosis and Acute Blood PressureSlide Number 37Blood Pressure and Hematoma EvolutionBP & OutcomeBP & OutcomeBP & OutcomeBP & OutcomeSo…Lower BP �Follow the guideline?Or…�Be ahead of the curveSlide Number 46Slide Number 47Prevent ICH GrowthPercent Change in ICH Volume at 24 HoursModified Rankin Scale at Day 90Hematoma Evolution and rFVIIaCTA Based rFVIIa Selection TrialsICH SummaryICH Summary�Beyond the GuidelinesICH Summary�Beyond the GuidelinesReferencesReferencesSlide Number 58