Epidemiology and Pathophysiology of Intracerebral Hemorrhage 1 Edward C. Jauch, MD MS FACEP

Epidemiology and Pathophysiology of

Intracerebral Hemorrhage

1 Edward C. Jauch, MD MS FACEP

Edward C. Jauch, MD MS FACEP

Assistant ProfessorAssociate Director of Research

Department of Emergency MedicineUniversity of Cincinnati College of Medicine

Faculty, Greater Cincinnati / Northern Kentucky Stroke Team

2

Edward C. Jauch, MD MS FACEP3

Global ObjectivesGlobal Objectives

• Review epidemiology of ICH

• Understand pathophysiology of ICH

• Discuss lessons from acute ischemic stroke

• Improve Emergency Medicine practice


A Clinical CaseA Clinical Case


Patient Initial Clinical HistoryPatient Initial Clinical History

• 57 yo male with sudden onset headache and left sided weakness

• Family calls 911

• EMS transport to OLFH Hospital

• Enroute patients symptoms progress to full hemiplegia

• Initial VS: 210 / 120 mmHg, HR 110, R 24


Patient ED PresentationPatient ED Presentation• PMHX: HTN for 10 years,

hyperlipidemia

• SHX: Smoking 30 years

• Meds: ACE inhibitor, ASA

• ROS: No recent illness or injuries, no new medications


Patient ED PresentationPatient ED Presentation• Physical examination:

• VS - 220 / 140 mmHg, HR 110, RR 22, T 98.6oC• Uncomfortable WM, arouses to voice• HEENT/CV/Lungs/Abd - WNL• Neuro –

• LOC mildly depressed• CN with L facial droop and partial gaze palsy, VFI• Motor with dense L hemiplegia• Sensory with mild L sensory loss• Speech slurred but no significant aphasia• NIHSS = 12


Key QuestionsKey Questions• What is your differential diagnosis?

• What are the most common ICH etiologies?

• What is the pathophysiology of ICH?

• What guidelines exist that govern the acute care of ICH patients?

• What can be learned regarding ICH management from acute ischemic stroke?

• How can the emergent care of ICH patients be enhanced?


Patient ED PresentationPatient ED Presentation

• Initial noncontrast CT scan

• Labs:– CBC, chem 7 – WNL

– PT, PTT – WNL

– ECG – LVH with strain


Stroke SubtypesStroke Subtypes

(NINCDS Stroke Data Bank: Foulkes, Stroke, 1988)

ICH13%

SAH13%

Lacunar19% Thromboembolic

6%

Cardioembolic14%

Other 3%

Unknown32%

Ischemic 71%

Hemorrhagic 26%

Up to 65,000 ICH per year in U.S.Up to 65,000 ICH per year in U.S.


ICH ClassificationsICH Classifications

• Primary– Hypertensive arteriopathies– Cerebral amyloid angiopathies

• Secondary– Neoplasms– Structural lesions – Anticoagulants or thrombolytic agents– Drugs (cocaine, ephedra, etc)– Traumatic brain injury


LocationLocation• Lobar

– Associated with amyloid angiopathy

• Nonlobar– Associated with hypertension

• Cerebellar• Intraventricular


Lobar HemorrhageLobar Hemorrhage

• Secondary to cerebral amyloid angiopathy– Beta-amyloid deposition in

vessels of cortex and leptomeninges

– Associated with aging

• Lobar hemorrhage in young due to AVM, cavernous hemangioma


Non-lobar HemorrhageNon-lobar Hemorrhage

• Non-lobar or hypertensive hemorrhage– Associated with hypertensive

arteriolosclerosis

• Location – putamen, pons, thalamus, cerebellum

• Mortality– 50% 30 day mortality

• Exam:– sudden HA with focal findings on exam


Risk FactorsRisk Factors

• Age

• Gender (men > women)

• Race (blacks > whites)

• Prior stroke

• Hypertension

• Anticoagulant / thrombolytics

• Alcohol / cocaine19 yo with ephedra 19 yo with ephedra

induced ICHinduced ICH


Less Common Risk FactorsLess Common Risk Factors

• Vascular malformations– Arteriovenous malformations (AVM)– Cavernous angiomas– Intracranial aneurysms

• Infections– Cerebral vasculitis– Mycotic aneurysms

• Cerebral venous thrombosis


ICH Rate by AgeICH Rate by Age

0

50

100

150

200

250

0-35 35-44 45-54 55-64 65-74 75-84 85+

Rate per 100,000 / year

Age (years)


Systolic Blood Pressure & Systolic Blood Pressure & IncidenceIncidence

0

50

100

150

200

250

<110 110-139 140-179 180+

Incidence Rate/100,000

Systolic Blood Pressure (mmHg)


Ethnicity of ICH RiskEthnicity of ICH Risk

• Age and sex adjusted rate– U.S. 15 per 100,000

– World wide 10-20 per 100,000

– Higher in African American and Japanese

• Rates 13.5 per 100,000 Caucasian38 per 100,000 AA55 per 100,000 Japanese


Anticoagulation and Thrombolytic Anticoagulation and Thrombolytic Related HemorrhageRelated Hemorrhage

• Warfarin anticoagulation– 6-11 fold increased risk of ICH– Higher levels with increased risk– Most occur in therapeutic range

• Thrombolysis and Symptomatic ICH– 6.4% in thrombolysis treatment group

• tPA related hemorrhages typically lobar• 20% occur outside area of infarct

– 0.6% in placebo group


Mortality and MorbidityMortality and Morbidity

• Estimated lifetime cost $123,565

• Of the 37,000-65,000 ICH per year

– 35-52% were dead at 1 month

– 50% of deaths occurred within 48 hours

– 10% independent at 30 days

– 20% independent at 6 months


30 Day Outcome of ICH30 Day Outcome of ICH

0

20

40

60

80

100

0 1 2 3 4 5 Dead

No. cases

Modified Oxford Handicap Scale


Clinical PresentationClinical Presentation

• Symptoms and signs– 82% change in mental status

– >75% hemiparesis/plegia

– 63% headache

– 22% vomiting

– 2/3 progression of symptoms, 1/3 maximal at onset


Clinical Presentation by LocationClinical 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


ICH ProgressionICH Progression

• Symptoms often progress, associated with ICH growth– 26% with 33% or greater growth in 1 hour

– 12% with 33% or greater growth 1-20 hours

• This gives us a window of therapeutic opportunity


Prognostic InformationPrognostic Information

• Volume of hemorrhage

• Clinical presentation

• Intraventricular extension

(Kothari, Stroke)


Hematoma Volume CalculationHematoma Volume Calculation

• Formula for volume of an ellipsoid– 4/3Л (A/2)(B/2)(C/2)

– Simplified ABC/2


PrognosisPrognosis• Worse

– Volume > 60 cm3 and GCS < 9• 91% dead at 30 days

– Patients with volume over 30 cm3 only 1 / 71 independent at 30 days

– Intraventricular extension

• Better– Volume < 30 cm3 and GCS 9 or higher

• 19% dead at 30 days

(Broderick, Stroke)


PathophysiologyPathophysiology• Initial hemorrhage into surrounding

tissues causes:– Cytotoxic and vasogenic edema formation in

the perihematomal parenchyma– Neurotoxicity from released serum proteins

• Elevated intracranial pressure due to– Hematoma mass effect – Perihematomal edema – Intraventricular extension and hydrocephalus– Results in decreased perfusion

Current Recommendations for Current Recommendations for Management of Intracerebral Management of Intracerebral

HemorrhageHemorrhage

(Broderick, Stroke 1999)

•Emergency Medicine representationEmergency Medicine representation

•New guidelines due 2005New guidelines due 2005



Emergent EvaluationEmergent Evaluation• Baseline labs

– CBC, coags, electrolytes

• Neuroimaging – CT remains gold standard

• Identify ICH• Identify complications (hydrocephalus, herniation)

– MRI / MRA • Useful to evaluate for structural abnormalities• AVM, aneurysms

– Angiography• Rarely emergently indicated• Identify vascular issues preoperatively in occult ICH


Medical ManagementMedical Management• ABC’s• Blood pressure control• ICP management

– Hyperventilation– Osmotherapy– No role for glycerol, corticosteroids, hemodilution

• Other– Prevention of hyperthermia– Fluid management (CVP at 5-12 mm Hg)

• Modifications for age, comorbidities, size, severity, location • Seizure control• Find somebody to take the patient


Blood Pressure ManagementBlood Pressure Management• No definitive data (yet)• Hypertension very common

– MAP > 140 in 34%, > 120 in 78%– Many return to baseline over first 24 hours

ProspectiveRetrospective Case Series Results

Meyer et al. 1962

Lower BP good

Dandapani et al. 1995

Lower BP good

Qureshi et al. 1999

Lower BP bad

Brott T et al 1995

Hematoma enlargement not associated with degree of HTN

(Dr. Aninda Acharya, St.Louis University, Internet Stroke Center)(Dr. Aninda Acharya, St.Louis University, Internet Stroke Center)

Blood Pressure ManagementBlood Pressure Management

(Broderick, Stroke 1999) Edward C. Jauch, MD MS FACEP34


Management of Increased ICP Management of Increased ICP • Definition

– ICP > 20 mm Hg for > 5 mins

• Treatment goal– ICP < 20 mm Hg– CPP > 70 mm Hg

• Recommendations– ICP monitoring with GCS < 9

• Management– Osmotherapy– Hyperventilation– Ventricular drainage

Management of ICPManagement of ICP

(Broderick, Stroke 1999) Edward C. Jauch, MD MS FACEP36


Seizure TherapySeizure Therapy• 25% will have seizure• Much more common if lobar• Most in first 72 hours• Phenytoin is drug of choice• Does not convey life long epilepsy


What can be Fixed?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


Surgical TreatmentSurgical Treatment

• Direct evacuation, endoscopic, stereotactic

Surgical Treatment Surgical Treatment RecommendationsRecommendations

(Broderick, Stroke 1999)

•7000 procedures a year in U.S. despite lack of data7000 procedures a year in U.S. despite lack of data•Largest surgical trial negative (in press)Largest surgical trial negative (in press)•MISTIE trial of stereotactic evacuation with tPAMISTIE trial of stereotactic evacuation with tPA

• (3/05) Surgery in 24 hrs, stable clot for 6 hrs(3/05) Surgery in 24 hrs, stable clot for 6 hrs

40

The Potential Future With Novo 7The Potential Future With Novo 7What Can We Learn From What Can We Learn From Acute Ischemic Stroke?Acute Ischemic Stroke?

41


Time Will Always Mean Brain!Time Will Always Mean Brain!

(Lancet (Lancet 2004; 363: 768–74)2004; 363: 768–74)

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

Same Chain: No Weak LinksSame Chain: No Weak Links

43


Emergent Triage and ED EvaluationEmergent Triage and ED EvaluationMust be a PriorityMust be a Priority


NINDS Recs: Same for ICHNINDS Recs: Same for ICH

• Door-to-MD: 10 minutes

• Door-to-Stroke 15 minutes Team notification:

• Door-to-CT scan: 25 minutes

• Door-to-Drug: 60 minutes (80% compliance)

• Door-to-Admission 3 hours

(NINDS Stroke Symposium 2003)(NINDS Stroke Symposium 2003)


There Will Be Major BarriersThere Will Be Major Barriers• EM education of disease and treatment• Timely radiology involvement• Access to neurologic expertise

– Neurology does not admit ICH– Neurosurgeons won’t rush in – EM will be point person like tPA

• Post treatment management– ICU beds– Complications likely to occur early

• Cost– Whose cost center– “Drip and ship” model


Who Cares for Patients with ICH?Who Cares for Patients with ICH?• Shortage of neurosurgeons• Shortage of neurocritical care • Neurologists not experienced with ICH• Emergency Medicine primarily focused on stabilization• Example – Cincinnati

– 30% neurosurgical shortage– Nonoperative ICH to neurology– Only 4 of 15 hospitals with neurosurgery coverage – Only 1 level 1 trauma largely due to neurosurgery


Potential Solution:Potential Solution:Utilize Primary Stroke CentersUtilize Primary Stroke Centers

• Patient care areas– Acute stroke teams

– Written care protocols

– EMS participation

– Emergency Department participation

– Stroke unit*

– Neurosurgical services**

• Support services– Organizational support– Stroke center director– Neuroimaging– Laboratory– Outcome & quality measures– CME

(Brain Attack Coalition, (Brain Attack Coalition, JAMAJAMA 2000) 2000)

• Secondary stroke center likely required for most ICH


ED Treatment and ED Treatment and Patient OutcomePatient Outcome


Questions??Questions?? www.ferne.orgwww.ferne.org

[email protected]@ferne.org

Edward Jauch, MD, MSEdward Jauch, MD, [email protected]

(513) 558-0474(513) 558-0474

ferne_acep_2005_jauch_ich_epipath_cd 04/20/23 12:56 AM

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Epidemiology and Pathophysiology of Intracerebral Hemorrhage 1 Edward C. Jauch, MD MS FACEP