Intracerebral Hemorrhage Contemporary Management

J. Teitlelbaum, MD, FRCP(C) McGill University Université de Montréal

CCCF Toronto October 2014

Conflicts of Interest

none

Objectives

Be aware of new ideas beyond the guidelines Stroke. 2010;41:2108-2129

Investigation

Monitoring

Therapy

Investigation

Guideline: Dx: non-contrast CT (MRI)

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

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

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

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

Primary SICH - Outcome

6 month prognosis dismal 40% dead within one month (half < 48H) 40% disabled and dependent 20% independent Main prognostic factor: volume

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%

Primary ICH Factors related to outcome

GCS on presentation Age Hemorrhage location Intra-ventricular hemorrhage Blood pressure on admission Hemorrhage size (expansion)

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%

Size is the most important predictor of patient outcome

DEAD FULL RECOVERY

Predicting ICH expansion

Time since onset

Spot sign

Blood pressure

Shape of the hematoma

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

CTA Source Images: Additional Data

Spot Sign

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

Investigation Follow the Guideline?

Not this part of the guideline CTA for all SICH

SICH - Monitoring

Traditional (guideline): Clinical exam SBP/MAP ICP / CPP Repeat CT @ 24H

SICH – Multi-modality Monitoring

Beyond the guideline (?? Useful) cEEG Non-invasive Brain O2 Intracranial monitoring:

PbtO2 (Licox) Microdialysis:

lactate/pyruvate/glutamate/glycerol/glucose

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)

cEEG Useful?

Seizures & PEDs associated with Neurologic worsening (NIHSS) in midline shift (p < 0.03) poor outcome

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

So… cEEG

Find the seizures that matter Treat Sz, and ? PEDs Avoid prophylaxis

Brain Tissue Oxygenation

Jugular venous bulb oxymetry Direct PbtO2 Near infrared spectroscopy Oxygen-15 PET

Brain Tissue Oxygenation

Licox intracranial PbtO2 T° dependent Samples 15 mm of tissue Usual indications

Diffuse injury Focal injury (SDH, contusion) SAH Infarction

2

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

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

SICH Treatment

Treatment Modalities

General supportive care Treatment of ICHT Hematoma resection Management of intra-ventricular hemorrhage

Seizure prophylaxis / treatment Prevention of hematoma growth BP management

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

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

Seizure prophylaxis

Guideline: No

Beyond the guideline No, if cEEG available Yes if unexplained LOC, first 48H cortical ICH Keppra (if can load)

Seizure Treatment

Guideline Treat clinical Sz Treat EEG Sz if unexplained or Δ in LOC Consider cEEG

Blood Pressure Management

Does BP affect prognosis? Can BP be lowered safely? Does this ICH growth? Does this affect outcome?

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 (%

)

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

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

BP & Outcome

Neurology Meta-analysis 2014 ADAPT (

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

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

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

So…

Aggressive By 6H post event ≤ 1H of arrival Very little effect on ICH growth Better outcome ?? Statistical effect??

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

Or… Be ahead of the curve

Aggressive (< 4-6H of event) Fast (

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

2.0 hours after onset 6.5 hours after onset

Prevent Early Hematoma Growth

Prevent ICH Growth

By BP ??

By rFVIIa

-20

-15

-10

-5

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

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

-10

-5

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

Percent Change in ICH Volume at 24 Hours

Boxes depict 98.3%

confidence intervals

29%

11% 14%

52% RR

16%

45% RR 62% RR

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

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

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

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

ICH Summary Beyond the Guidelines

Investigation: CTA on all patients

Monitoring: Add cEEG for 48H PbtO2: not yet NIRS: coming soon

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

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

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

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