Current Management of Intracerebral Hemorrhage

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Current Management of Intracerebral Hemorrhage
2
Edward C. Jauch, MD, MS

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

3
Disclosure

• Novo Nordisk
• Consultant Site investigator phase III trial
• American Heart Association
• ASA and ACLS Stroke Guidelines Committee
• Various AHA Committee
• National Institutes of Health
• Ventricular and hematoma aspiration trials
• (Genentech providing drug)

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Global Objectives

• Review epidemiology of ICH
• Discuss current treatment recommendations
• Review recent developments in ICH treatment
• Discuss lessons from acute ischemic stroke

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A Clinical Case
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Patient Initial Clinical History

• 57 yo male develops sudden onset headache and
  left sided weakness
• Family calls 911 (112, 115, etc)
• EMS transport to hospital
• Symptoms progress to full hemiplegia
• Initial VS 210 / 120 mmHg, HR 110, R 24

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Patient ED Presentation

• PMHX Hypertension for 10 years,
  hyperlipidemia
• SHX Smoking 30 years
• Meds ACE inhibitor, ASA
• ROS No recent illness or injuries No new
  medications

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Patient ED Presentation

• Physical examination
• VS - 220 / 140 mmHg, HR 110, RR 22, T 98.6oF
• Neuro (NIHSS 12)
• LOC mildly depressed (GCS 13)
• Left facial droop partial gaze palsy
• Dense left hemiplegia
• Mild left sensory loss
• Speech slurred
• Laboratory and ECG normal
• Neuroimaging shows

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Key Questions

• What is your differential diagnosis?
• What medical management should be initiated in
  this patient?
• What additional imaging is required?
• What laboratory tests should be completed?
• What are treatment options and issues?

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Stroke Subtypes
Up to 65,000 ICH per year
(Foulkes, NINCDS Stroke Data Bank Stroke, 1988)
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ICH Classifications

• Primary (80)
• Hypertensive arteriolopathies
• Cerebral amyloid angiopathies
• Secondary (20)
• Vascular abnormalities
• Neoplasms
• Coagulation disorders
• Anticoagulants or thrombolytic agents
• Drugs (cocaine, ephedra, etc)
• Trauma

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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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Clinical Presentation

• Symptoms and signs
• 82 change in mental status
• gt75 hemiparesis/plegia
• 63 headache
• 22 vomiting
• Symptoms
• 2/3 with progression of symptoms
• 1/3 maximal at onset

(Brott, Stroke 1997281-5)
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Clinical Presentation by Location

• Lobar
• Headache (headache location related to ICH site)
• Motor, sensory deficit, or VF deficits (not all)
• Deep
• Unilateral motor, sensory, VF loss
• Aphasia (D) or neglect (ND)
• Cerebellum
• Nausea, vomiting, ataxia, coma
• Pontine
• Coma, quadriplegia, pinpoint pupils

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Primary Risk Factors

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

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

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Pathophysiology

• Initial hemorrhage into tissues causes
• Cytotoxic and vasogenic edema formation
• Mediators MMP-9, inflammatory response, blood
  degradation products
• Elevated intracranial pressure due to
• Hematoma mass effect
• Perihematomal edema
• Intraventricular extension and hydrocephalus
• Decreased regional perfusion and herniation

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ICH Progression

• Symptoms often progress, associated with ICH
  growth
• Within 3 hours from onset
• 26 with 33 or greater growth in next 1 hour
• 12 with 33 or greater growth 1-20 hours

(Brott, Stroke 1997281-5)
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Prognosis

• Worse
• Volume gt 60 cm3 and GCS lt 9
• 91 dead at 30 days
• Patients with gt 30 cm3
• 1 / 71 independent at 30 days
• Other age, seizures, intraventricular extension
• Better
• Volume lt 30 cm3 and GCS 9 or higher
• 19 dead at 30 days

(Broderick, Stroke 199324987- 93)
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28 mL
43 mL
(Image courtesy T. Brott, MD)
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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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Mortality and Morbidity

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

patients
Modified Oxford Handicap Scale
(Broderick, Stroke 199324987- 93)
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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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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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ICH Management

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

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Medical Management

• ABCs
• Maintain oxygen saturation 92
• Rapid sequence intubation
• Medical management
• Prevention of hyperthermia (lt37.5oC)
• Glycemic control (lt10 nmol/L)
• Coagulopathy correction (FFP, vitamin K)
• No glycerol, corticosteroids, hemodilution
• Secondary complication prevention

(EUSI, Cerebrovasc Dis 200316311-318)
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Blood Pressure Management

• Hypertension very common
• MAP gt 140 in 34, gt 120 in 78
• Many normalize over first 24 hours
• General goals
• Maintain MAP lt 130 mmHg with history of
  hypertension
• Prevent hypotension (SBP lt 90 mmHg)
• Maintain
• Cerebral perfusion pressure (CPPMAP-ICP) CPP gt
  70 mmHg
• Central venous pressure from 5-12 mmHg
• Optimal blood pressure still to be determined

 
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Blood Pressure Management

• For now -
• Common agents
• Labetalol
• Nicardipine
• Nitroprusside
• (theoretical risk of
• increasing ICP)
• New data suggest SBP lt 150 mm Hg

(Broderick, Stroke 199930(4)905-15) (Ohwaki,
Stroke 2004351364-1367)
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Management of ICP

• Definition
• ICP gt 20 mm Hg for gt 5 minutes
• Treatment goal
• ICP lt 20 mm Hg and CPP gt 70 mm Hg
• Recommendations
• ICP monitoring with GCS lt 9
• 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 lt 310 mmol/L
• 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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Seizures

• More common in ICH than you think
• Over 25 will seizure (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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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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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
lt 3 hours
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
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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
Placebo 40 µg/kg 80 µg/kg 160 µg/kg P Value
2 6 4 10 0.12

• 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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Potential Future Tools

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

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What Can We Learn From Acute Ischemic Stroke?
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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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NINDS RecommendationsSame for ICH?

• Door-to-MD 10 minutes
• Door-to-Expert? 15 minutes
• Door-to-CT scan 25 minutes
• Door-to-Drug 60 minutes
• Door-to-Admission 3 hours

(NINDS Stroke Symposium 2003)
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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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ED Treatment Patient Outcome

• Patients GCS declined to 11 over 48o
• Mild edema shift seen on 48o CT
• Blood pressure managed with labetalol
• Patient required inpatient rehab
• Moderately disabled at 3 months but at home

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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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Key Role of Emergency Medicine
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Questions??

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

ferne_2005_aaem_france_jauch_ich_fshow.ppt
8/29/2005 145 AM
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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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ICH Rate by Age
Incidence rate / 100,000 per year
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Systolic Blood Pressure Incidence
Incidence rate / 100,000 per year
Systolic Blood Pressure (mmHg)
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Prognostic Information

• Hemorrhage volume
• Clinical presentation / Initial GCS
• Age
• Intraventricular extension
• Use of anticoagulants
• Associated seizures

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Similar Pathophysiology