Ten Things to Know in Intracerebral Hemorrhage

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Ten Things to Know in Intracerebral Hemorrhage
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Edward C. Jauch, MD, MS

• Assistant ProfessorDirector of
  ResearchDepartment of Emergency
  MedicineUniversity of Cincinnati College of
  MedicineFaculty, Greater Cincinnati / Northern
  Kentucky Stroke Team

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Disclosure

• Novo Nordisk
• Consultant Site investigator phase III trial
• American Heart Association
• ASA and ACLS Stroke Guidelines Committee
• Various AHA Committees
• NINDS ventricular and ICH aspiration trials
• Genentech providing drug

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Point 1

• Intracerebral Hemorrhage is Bad!

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Ethnicity of ICH Risk

• Age and sex adjusted rate
• U.S. 15 per 100,000
• World wide 10-20 per 100,000
• Rates 13.5 per 100,000 Caucasian 38 per
  100,000 African Americans 55 per 100,000
  Japanese

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Mortality and Morbidity

• Outcome
• 35-52 dead at 1 month
• 50 of deaths within 48o
• 10 independent at 30 days
• 20 independent at 6 mos
• Lifetime ICH cost 125K

patients
Modified Oxford Handicap Scale
(Broderick, Stroke 199324987- 93)
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Point 2

• Intracerebral Hemorrhage is Like Acute Ischemic
  Stroke
• Sort of

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Similar Pathophysiology
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Primary Risk Factors

• Age
• Hypertension
• Alcohol intake
• Gender (M F)
• Race
• Smoking
• Diabetes

• Vascular malformations
• Moyamoya / aneurysms
• Infections
• Vasculitis
• Mycotic aneurysms
• Cerebral venous thrombosis
• Genetic
• Apolipoprotein E e4

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Location

• Lobar
• Associated with amyloid angiopathy
• Nonlobar
• Due to hypertension
• Cerebellar
• Brain stem

Cortex
Thalamus
Basal ganglia
Pons
Cerebellum
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Point 3

• ICH is Dynamic

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ICH Progression

• Symptoms often progress, associated with ICH
  growth
• 2/3 with progression of symptoms
• 1/3 maximal at onset
• Within 3 hours from onset
• 26 with 33 growth in next 1o
• 12 with 33 growth 1-20o

(Brott, Stroke 1997281-5)
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Point 4

• Size Matters

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28 mL
43 mL
(Image courtesy T. Brott, MD)
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Prognosis

• Worse
• Volume 60 cm3 and GCS
• 91 dead at 30 days
• Patients with 30 cm3
• 1 / 71 independent at 30 days
• Other age, seizures, intraventricular extension
• Better
• Volume
• 19 dead at 30 days

(Broderick, Stroke 199324987- 93)
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Hematoma Volume

• Formula for volume of an ellipsoid
• 4/3p (A/2)(B/2)(C/2)
• Simplified ABC / 2

C
B
A
(Kothari, Stroke 1996271304-5)
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Point 5

• Medical Management
• The Basics are Important

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Current Recommendations for Management of
Intracerebral Hemorrhage
New guidelines due 2005
(Broderick, Stroke 199930(4)905-15)
Edward C. Jauch, MD MS FACEP
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ICH Management

• Immediate stabilization (ABCs)
• Supportive medical care
• Frequent comorbidities
• Neurologic specific care
• Hemorrhage specific interventions

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Emergent Evaluation

• Baseline labs
• CBC, coagulation parameters, electrolytes
• Neuroimaging
• CT remains gold standard
• Identify ICH and complications (hydrocephalus,
  herniation)
• MRI / MRA
• For structural abnormalities (AVM, aneurysms)
• Angiography
• Rarely emergently indicated, identifies vascular
  issues

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Medical Management

• ABCs
• Maintain oxygen saturation 92
• Rapid sequence intubation
• Medical management
• Prevention of hyperthermia (
• Glycemic control (
• Coagulopathy correction (FFP, vitamin K)
• No glycerol, corticosteroids, hemodilution
• Secondary complication prevention

(EUSI, Cerebrovasc Dis 200316311-318)
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Point 6

• Medical Management is Important
• Blood Pressure

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Blood Pressure Management

• Hypertension very common
• MAP 140 in 34, 120 in 78
• Many normalize over first 24 hours
• General goals
• Maintain MAP hypertension
• Prevent hypotension (SBP
• Maintain
• Cerebral perfusion pressure (CPPMAP-ICP) CPP
  70 mmHg
• Central venous pressure from 5-12 mmHg
• Optimal blood pressure still to be determined

 
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Blood Pressure Management

• Common agents
• Labetalol
• Nicardipine
• Nitroprusside
• (theoretical risk of
• increasing ICP)
• New data suggest SBP

(Broderick, Stroke 199930(4)905-15) (Ohwaki,
Stroke 2004351364-1367)
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Point 7

• Medical Management is Important
• Intracranial Pressure

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Management of ICP

• Definition
• ICP 20 mm Hg for 5 minutes
• Treatment goal
• ICP 70 mm Hg
• Recommendations
• ICP monitoring with GCS
• Management
• Patient positioning
• Osmotherapy
• Hyperventilation
• Ventricular drainage

 
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Management of ICP

• Osmotherapy
• Mannitol 0.25-0.5 g/kg every 6 hours up to 5 days
• Target mOsm
• Hyperventilation
• Tidal volume of 12-15 ml/kg
• Target pCO2 30-35 mm Hg
• Neuromuscular paralysis
• Nondepolarizing agents

(Broderick, Stroke 199930(4)905-15)
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Point 8

• Medical Management is Important
• Seizures

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Seizures

• More common in ICH than you think
• Over 25 will seize (vs 6 for ischemic stroke)
• Much more common if lobar
• Focal with secondary generalization
• Most in first 72 hours
• Treatment
• Phenytoin (minimizes sedation)
• Does not convey life-long epilepsy

(Vespa, Neurology 2003601441-6)
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Point 9

• Medical Management is Important
• Coagulation Correction

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Coagulation Correction

• Warfarin
• FFP 10 ml/kg
• Vit K 10 mg IV over 10 mins
• Heparin (and some LMWH)
• Correct with protamine 10 50 mg IVP over 1 3
  mins
• Direct thrombin inhibitors
• No antidote, consult hematology
• Platelet disorders
• Correct with platelets (100,000)
• DDAVP 0.3 µg/kg IV over 30 mins

(MGH Stroke Service, 2005)
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Point 10

• There is Hope
• on the Horizon

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What can be Fixed?

• Stop the bleeding
• Until now no option?
• Remove the blood
• Multiple trials without clear impact
• Reduce the edema
• No treatment yet

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Potential Future Tools

• Surgery
• Surgical patient selection and new approaches
• Stereotactic evacuation with tPA
• Intraventricular evacuation with fibrinolysis
  (ITT, DITCH)
• Medical therapies
• Optimizing blood pressure (ATACH)
• Tight glycemic control (THIS)
• Neuroprotectives (CHANT, Fast-MAG, hypothermia)
• Ultra-early hemostatic therapy (rFVIIa)

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Surgical Treatment

• Direct evacuation, endoscopic, stereotactic

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Surgical Treatment Recommendations

• 7000 procedures a year in U.S. despite lack of
  data
• STICH Largest surgical trial without general
  benefit

(Mendelow, 2005365387-97) (Broderick,
199930(4)905-15)
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Hemostatic Therapy

• Few late studies (mostly in SAH)
• Aminocaproic acid
• Tranexamic acid
• Ultra-early studies
• rFVIIa
• Pilot (n48)
• F7ICH-1371 (n399)
• Phase III (n675) ongoing

(Mayer, Stroke 20053674-79) (Mayer, NEJM
2005352777-785)
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Study Design
24-72 hours
90 days

• 2 Efficacy
• Mortality
• mRS
• Barthel Index
• E-GOS
• NIHSS
• GCS
• Euro-QOL

CT Baseline
CT 24 h
CT 72 h
Patients presenting with stroke-like symptoms
1 Efficacy Percent change in ICH volume at 24
hours
Baseline CT scan

• Safety
• Adverse events until discharge
• Serious adverse events until day 90
• Exacerbation of edema

20 Countries 73 Trial Sites
(Mayer, NEJM 2005352777-785)
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Estimated Mean Percent Change in ICH Volume at 24
Hours
Percent Change in ICH Volume by Treatment

70
52 RR
45 RR
62 RR
65
60
55
50
45
40
35
30
29


25
20

16
14
14
15
11
10
5
0
-5
-10
-15
-20
CombinedTreatment Groups
Placebo
40 µg/kg
80 µg/kg
160 µg/kg
Treatment Groups
Combined treatment groups vs placebo P 0.0112.
(Mayer, NEJM 2005352777-785)
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Modified Rankin Scale at Day 90
01 no significant disability
160 µg/kg
23 slight to moderate disability
80 µg/kg
45 moderately severe to severe disability
40 µg/kg
Placebo
100
80
60
40
20
0
6 dead
29 vs 18 rFVIIa vs placebo, RRR 38,
Chi-square test P 0.02
(Mayer, NEJM 2005352777-785)
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Thromboembolic SAEs
Frequency of Thromboembolic SAEs

• Arterial thromboembolic SAEs (myocardial ischemia
  7 and cerebral infarction 9) with rFVIIa
  treatment (5) vs placebo (0), P 0.01
• Fatal or disabling thromboembolic SAEs in 2 of
  rFVIIa-treated patients compared with 2 in the
  placebo group
• Nonsignificant dose trend in events (P 0.12)

(Mayer, NEJM 2005352777-785)
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Bonus Point

• Learn from Your Mistakes

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Time Will Always Mean Brain!

• ICH continue to expand
• Early medical management essential
• Early coagulation correction critical (drip and
  ship)
• Hemostatic therapy may work best early

(Lancet 2004 363 76874)
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Same Chain No Weak Links

• Development Protocol and pathway development
• Detection Early recognition
• Dispatch Early EMS activation
• Delivery Transport management
• Door ED triage
• Data ED evaluation management
• Decision Neurologic input, therapy selection
• Drug Thrombolytic (hemostatic) agents
• Disposition Admission or transfer

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There May Be Major Barriers

• Education
• Timely radiology involvement
• Access to neurologic expertise
• Post treatment management
• Availability of ICU beds
• Complications occur early
• Resources and cost

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Key Learning Points

• ICH is a dynamic process
• Critical management frequently required and
  required early
• General management impacts outcome
• Targeted therapies time dependent
• Hemostatic therapies may play a role if
  administered early
• Surgery for selected cases

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Questions?

• www.ferne.orgferne_at_ferne.orgEdward C. Jauch,
  MD, MSedward.jauch_at_uc.edu