Transcript AHD 2012 Sep 19_ICH_Course2_Teitelbaum_MNI
Intracerebral Hemorrhage McGill Lecture Series Montreal, QC September 19, 2012 J. Teitlelbaum, MD, FRCP(C) University of McGill
Case History G.S.
68 year old R HBP, DB2, CAD 5PM, sudden R paresis Aphasia Ø headache, N or V
G.S.
Exam on arrival BP 190/100 P 75/min Alert, aware, mixed moderate aphasia CN: PERL, RHHA, R UMN VII, R ↓↓ sensation 2/5 strength R UE & LE ↓↓ sensation R hemi-body
CT 5:30PM
G.S. Sudden Deteriororation
Exam at 7PM GCS 10, very somnolent, not obeying commands, groans & opens eyes to voice.
Pupils 4mm L 3mm R reactive Poor airway protection Power 0/5 R UE & LE
CT at 7:05 PM
G.S. Now what ??
ICH Epidemiology & Etiology : primary vs secondary Factors that affect prognosis Management Evidence-based Eminence based Experimental & anecdotal
The Guidelines
Broderick J, Connolly S, Feldmann E, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: Circulation. 2007;116:e391–413.
ICH Incidence in 2003 120,000 100,000 80,000 60,000 40,000 20,000 0 USA Japan EU5
Intracerebral Hemorrhage
15% of stroke in the West, 30% in the East 6 month prognosis dismal 40% dead (33% within 1 month) 40% disabled and dependent 20% independent
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
Dismal Prognosis
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Dead ICH Dependent Ischemic Independent
Factors Affecting Prognosis
GCS on presentation Age Hemorrhage location Intraventricular hemorrhage ? Blood pressure Hemorrhage size
Secondary Damage
Hematoma expansion ≥ 80 ml fatal Cerebral edema Secondary injury
Component
GCS 3 - 4 5 - 12 13 - 15 ICH volume ≥ 30 ml ≤ 30 ml IVH yes no Infratentorial Age > 80
ICH Score
ICH score points
1 0 2 (34/35 died) 1 (29/57 died) 0 (5/60 died) 1 0 1 1
Mortality and ICH Score
The relationship between ICH volume and patient outcome FULL RECOVERY DEAD
Size is the most important predictor for patient outcome
38 ml 43 ml
A patient with a haemorrhage the size of a ping pong ball is likely to have a better outcome than a patient with a haemorrhage the size of golf ball: –mortality on ’ping pong’ size: app. 40% –mortality on ’golf ball’ size: app. 70%
Which are Modifiable ?
GCS on presentation Age Hemorrhage location Intraventricular hemorrhage
? Blood pressure
Hemorrhage volume
Early growth occurs in all locations Initial CT time Putamen Thalamus Lobar Cerebellar Pons Other Brott (1997) N=103 0-3 hrs 34% 50% 32% 0% 40% 43% TOTAL 38% Kazui (1994) N=186 0-24 hrs 16% 21% 29% 25% 40% 25% 22% Fujii (1996) N=359 0-24 hrs 19% 10% 6% 12% 28% 13% 14%
3 h
Hematoma Evolution
3 h 2 h 6 h 24 h 24 h
Predicting ICH expansion
Time since onset Spot sign Blood pressure Shape of the hematoma
CTA Source Images: Additional Data
Spot Sign
The Spot Sign: Growth Despite Treatment
2 hours 3 hours (CT Angiogram) 24 hours
rFVIIa
Predictive Value of Spot Sign: Time Dependent?
3 hours 4.5 hours 24 hours Spot Sign
Early Growth: Conventional angiography
Prognosis and Acute Blood Pressure
100
↑ Early Neurological Deterioration ↓ Functional Outcome (90 days)
80 60 40 20 0 -117 118-132 133-144 MAP (mm Hg) 145-
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 140 mmHg No Enlargement 16 150 mmHg 160 mmHg 170 mmHg 14 22 8 Hematoma Enlargement 2 1 8 5 9% p=0.025
30%
Ohwaki et al, Stroke, 35: 1353-1367, 2004
ICH Management
Treatment Modalities
General supportive care Treatment of ICHT Hematoma resection Management of intra-ventricular hemorrhage Seizure prophylaxis Prevention of hematoma growth BP management
Basic Algorithm
ABC ’ s Do no harm Pain management & sedation Hyperventilation pCO2 30-35 mm Hg Osmotic therapy Ventricular drainage
General Supportive Care
HOB 30 ° SO2 ≥ 95% Glucose control ≤ 6.0 mmol T ° control ≤ 37.5
° C Pain control, sedation
Hyperventilation
Regional blood flow Oxygen extraction But: CMRO 2 stable ad pCO2 = 10 mm Hg At the levels used in TBI, hyperV does not result in ischemia Pressure autoregulation dysfunction is improved
Hyperventilation
Present recommendation: Avoid during 1 st 24H post TBI pCO2 30 – 35 mm Hg If no response: 25 – 30 mm Hg
Hyperventilation
My recommendation: Use for acute ICHT, temporizing measure pCO2 30 – 35 mm Hg 25 – 30 mm Hg Has no associated ischemia ad pCO2 10 Beware of hypoperfused areas that are more fragile
Osmotic Agents Mechanisms of Action
Mannitol
BW in intact > affected brain
volume vasoconsriction viscosity CBF vasoconstriction size of CVA, apoptosis HS
BW in intact = affected brain
Possible in size of CVA
Osmotic Agents Clinical Use
Routinely recommended in edema of trauma and stroke Lack of evidence of beneficial outcome Little evidence of efficacy in stroke or ICH (especially Na)
Osmotic Agents Clinical Use
Intermittent boluses allowing clearing of solute from blood.
Avoid continuous infusions Smallest doses at the largest possible intervals, with prn according to ICP
Osmotic Agents Clinical Use
ICH with ICHT: MN first HS if refractory, Cr, OG Refractory to one agent: use the other 250cc MN, then 100cc alternating MN/HS
Treatment of ICHT
Intubation Hyperventilation Sedation Steroids: NO role Osmotic agents Mannitol Hypertonic saline No Δ in outcome
Hematoma Resection
STICH trial ICH within a centimeter of the cortical surface showed a benefit for early surgery mortality, no other effect on morbidity MISTIE: Intra-lesion rtpa with subsequent aspiration
Intra-ventricular Hemorrhage
EVD Intra- ventricular rtpa (CLEAR)
Intra-ventricular rTPA
Hanley DF: pilot, prospective, randomized, double-blind, controlled trial Speeds clearance of aneurysmal intraventricular hemorrhage Normalizes intracranial pressure Reduces ventricular catheter obstruction
Early Hematoma Growth
2.0 hours after onset 6.5 hours after onset
Prevent ICH Growth
By BP By rFVIIa
10 5 0 - 5 - 10 - 15 - 20 70 65 60 55 50 45 40 35 30 25 20 15
Percent Change in ICH Volume at 24 Hours
Percent Change in ICH Volume by T reatment Boxes depict 98.3% confidence intervals
29% 16% 14% 11%
10 5 0 - 5 - 10 - 15 - 20 70 65 60 55 50 45 40 35 30 25 20 15 Placebo 40 ug/kg rFVIIa 80 ug/kg rFVIIa 160 ug/kg rFVIIa
160 µg/kg
Modified Rankin Scale at Day 90
80 µg/kg
mRS 0-1 mRS 2-3 mRS 4-5 mRS 6
40 µg/kg Placebo
100% 80% 60% 40% 20% 0%
Hematoma Evolution and rFVIIa
Onset-CT interval (h )
0-3 3-6 6-24
Prospective
Brott 38% N/A N/A
Retrospective
Fujii 18% Kazui
3.3ml
36% Takizawa
4.5ml
17%
5.8ml
8% 16% 6% rFVIIa within 4 hours:
• • Dose dependent attenuation of hematoma
2% 10% 0%
no effect on mRS at 90 days Mayer et al. NEJM 2005; 352: 777-85
CTA Based rFVIIa Selection Trials
The S po T sign f O r P redicting and treating I CH grow T h study: STOP-IT SPOTRIAS/NINDS PI: M. Flaherty ‘ SPOT sign ’ se L ection of I ntracerebral hemorrhage to G uide H emostatic T herapy: SPOTLIGHT CSN/ CIHR PI: D. Gladstone
Acute ICH < 6 hours CTA Spot Sign Positive rFVIIa Placebo NCCT at 24 hours Spot Sign Negative
Seizure Prophylaxis
Are seizures frequent post ICH ?
Do they change outcome ?
Does prophylaxis frequency ?
Does a in Sz affect outcome ?
Is therapy associated with adverse events ?
Are seizures frequent post ICH ?
↑early Sz and late epilepsy (2003-2004) 1/3 pts: 50% electrographic (Neurology 2007)
Do they change outcome ?
Associated with expanding hemorrhages ICU stay Greater treatment cost edema, midline shift, re-bleeding, decreased functional recovery likelihood of poor long-term outcomes
Does prophylaxis
Sz frequency ?
Redding et al 2011: No (DPH) Taylor 2011 Neurocrit Care: Yes (Keppra) 21% vs 16%
Does a
in Sz Improve Outcome
Taylor 2011 Neurocrit Care: Yes (Keppra) Improved cognitive outcome vs DPH No untreated group CHANT study 2009: No (DPH mainly)
So…
There is an ↑in Sz post ICH (lobar) There is a likely effect on outcome Rx do ↓ Sz incidence This MAY improve outcome (Keppra IV)
ICH BP Management
Does BP affect outcome ?
Does BP affect the penumbra?
Does BP influence ICH growth?
Does treatment alter any of these??
Prognosis and Acute Blood Pressure: ICH n=425 n=1097 MAP (mm Hg)
Fogelhom et al, Stroke, 28: 1396-400, 1997 Okumura et al, J. Hypertension, 23: 1217-23, 2005
Acute BP Management: Competing Rationales
Impaired Autoregulation IV therapy suggested only for Systolic BP ≥ 180 mmHg (AHA Guidelines)
Guidelines for Acute BP Management: ICH
Stroke Council, American Heart Association IV therapy suggested only for Systolic BP ≥ 180 mmHg (or MAP > 130 mmHg) 2007: Consider target of 160 mmHg systolic, IF ↑ ICP not suspected
Acute ICH BP Treatment Trials
Trial ATACH n=60 INTERACT n=400 ICH ADAPT n=164 Target Blood Pressure 170-200; 140-170; 110-140 systolic <140 mmHg systolic <150 mmHg systolic Agent(s) Nicardipine Multiple Labetalol ± Hydralazine
Blood Pressure and Hematoma Evolution
Target max SBP 140 mmHg No Enlargement 16 Hematoma Enlargement 2 150 mmHg 160 mmHg 170 mmHg 14 22 8 1 9% p=0.025
8 30% 5 Ohwaki et al, Stroke, 35: 1353-1367, 2004
Temporal Profile of BP after ICH
Blood Pressure over time in the three different target groups
220.00
200.00
180.00
160.00
140.00
120.00
B as el in e 1 ho ur 3 ho ur s 5 ho ur s 7 ho ur s 12 h ou rs
Time
Systolic target <160mmHg Systolic target 160 179mmHg Systolic target >180mmHg
INTERACT: Efficacy of Antihypertensives
Target achieved: 42% (1h) 66% (6h) Drugs Used: 1. Furosemide 2. Urapidil
INTERACT: Hematoma Expansion
Rationale for Not Treating Blood Pressure
Based on Dirangl and Pulsinelli, JCBFM, 1990 (SHR ICAO/MCAO)
Autoregulation in ICH
160 150 140 130 120 First CTP 30 minutes 60 minutes 90 minutes Second CTP
Peri-hematoma Edema and Injury
Ischemic?
Vasogenic?
Pc Astrocyte Plasma Extravasation Capillary
Perihematoma Edema is Not Cytotoxic
Butcher et al,
Stroke
35:1879-1885, 2003
Peri-hematomal Oligemia: CT Perfusion
Peri-hematoma Oligemia: rCBF
* * P=0.01
Penumbral Threshold
Extreme BP Reduction and CBF
Tie Time (minutes)
Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT) Protocol Acute ICH - onset within 24 hours SBP ≥ 150 mmHg Randomization (N=74) Target SBP <150 mmHg Target SBP <180 mmHg
Labetalol ± Hydralazine
Primary Endpoint: rCBF measured with CT perfusion 2 hours after randomization
Butcher et al, IJS, 2010
So…
in BP will prevent hematoma growth if: Within 1 hour To ≤ 160 mm Hg systolic Labetalol / Hydralazine BP does CBF but no in ischemia Ideal BP: 150 – 160 mm Hg systolic
ICH Summary
Poor prognosis Hematoma expands early (≤4h) ICH Expansion can be predicted HBP is a likely factor in prognosis Expansion Edema formation other
ICH Summary
Treatment: General Prevention of ICH enlargement: BP within 1h to ≤ 160 mm Hg syst rFVIIa Seizure prophylaxis: likely useful (Keppra IV) ICHT therapy: no Δ in outcome Sx: little if any benefit