Ischemic Anterior Circulation Stroke Edward C. Jauch, MD, MS Assistant Professor Department of Emergency Medicine University of Cincinnati College of Medicine Cincinnati, OH and Greater Cincinnati/Northern Kentucky Stroke Team

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Ischemic Anterior Circulation StrokeEdward C.
Jauch, MD, MSAssistant ProfessorDepartment of
Emergency MedicineUniversity of Cincinnati
College of MedicineCincinnati, OHandGreater
Cincinnati/Northern Kentucky Stroke Team
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Lecture Goals

• Review Emergency Department evaluation of acute
  ischemic stroke
• Identify symptoms of anterior circulation stroke
• Identify issues specific to thrombolytic therapy
  in acute stroke
• Identify treatment options for acute ischemic
  stroke

Introduction
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61 year old male, with acute aphasia, right
facial droop, and right sided weakness

• 1230 Sudden onset while working in yard
• 1245 Family calls 911
• 1305 Advanced squad evaluates and
  rapidly transports
• 1315 Squad notifies receiving hospital
  of possible stroke
  patient

Case
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61 year old male with possible stroke arrives at
Our Lady of Faint Hope

• 1330 ED triage and physician evaluation
• 1345 Stroke Team responds
• 1400 CT scan performed
• 1415 Discuss with family and PMD
• 1420 Labs back gluc 97 BP remains 150/70s

Case
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Neurologic ExaminationNIH Stroke Scale
Case
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61 yo male with possible stroke

• 1420 CT reading No hemorrhage or early
  ischemia
• 1425 Checklist done No exclusion
  criteria met
• 1430 Decision time

Case
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Impact of Stroke

• 3rd leading cause of death in the U.S.
• A leading cause of adult disability
• 600,000 new strokes per year in U.S.
• 85 are ischemic

Introduction
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Death Rates from Stroke
(Dept Health and Human Services)
Epidemiology
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Stroke Outcomes

• In the 4.5 million US stroke survivors
• 10 Recover almost completely
• 25 Recover with minor impairments
• 40 Experience moderate to severe
  impairments requiring special care
• 10 Require care in a nursing home or other
  long-term care facility
• 15 Die shortly after the stroke

(NSA, 2001)
Outcomes
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Stroke Outcomes

• Medical morbidity associated with stroke
• 30 Develop pneumonia within first month
• 10 Risk of recurrent stroke per year
• 10 Deaths post-stroke from pulmonary
  embolisms
• Other morbidity from stroke
• 23 Develop multi-infarct dementia
• 70 Develop depression (27 major)
• 40 Depression common among care-givers

High end of estimates
Outcomes
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Stroke Risk Factors

• Modifiable risk factors
• High blood pressure
• Cigarette smoking
• Transient ischemic attacks
• Heart disease
• Diabetes mellitus
• Hypercoagulopathy
• Carotid stenosis
• Other

• Unmodifiable risk factors
• Age
• Gender
• Race
• Prior stroke
• Family History
• Other possible risk factors
• Sickle cell disease
• Apolipoproteins
• Others

Epidemiology
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Influence of Initial Medical Contacton Arrival
Times to the E.D.
(Barsan, Arch Int Med, 1993)
Epidemiology
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Detection

• What are Signs Symptoms?
• 43 general public didnt know any
• 39 of acute stroke patients didnt know any
• What are Risk Factors?
• 32 general public didnt know any
• 43 of acute stroke patients didnt know any

(Pancioli JAMA 1998 Kothari Stroke 1997)
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Where Are We Today?

• Poorly informed
• Too slow
• Too late
• Ill prepared
• Fatalistic

Epidemiology
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Forces of Change

• Public expectations
• Aware of Draino for the Braino
• Nihilistic attitude of stroke changing
• Medical - legal pressures
• Managed care cost concerns
• New treatments of stroke on horizon
• Change in treating physicians perceptions of
  risk

Epidemiology
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Organized Stroke Care Saves Lives

• 21 reduction in early mortality
• 18 reduction in 12 month mortality
• Decreased length of hospital stay
• Decreased need for institutional care

(Jorgensen, Stroke 1994)
Epidemiology
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Patient Aversion to Various Stroke Outcomes
Aversion
(Solomon, Stroke 1994)
Epidemiology
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Tissue-Plasminogen Activator inAcute Ischemic
Stroke

• Double-blinded, randomized
• Placebo controlled
• 0.9 mg / kg IVP dose
• 624 patients
• Treated within 3 hours
• 1/2 within 90 minutes
• 1/2 within 91-180 minutes

Management
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Benefits of Thrombolyticsin the NINDS Trial
For every 16 patients
No/Minimal Moderate
Severe Dead
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Relationship of Time to Thrombolytic
Treatment Odds Ratio of Favorable Outcome
Time is Brain!
Odds Ratio for Favorable Outcome at 3 Months
Benefit for rt-PA No Benefit for rt-PA
Minutes from Stroke Onset to Start of Treatment
Management
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Symptomatic Hemorrhages by CT Findings in NINDS
Trial
Percent of Patients that Developed Symptomatic
Hemorrhages

Edema or Mass Effect Seen on Initial CT
(Broderick, Stroke 1997)
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Symptomatic Hemorrhages by Baseline NIHSS in the
NINDS Trial
Percentage of t-PA Patients with Symptomatic ICH
(Broderick, Stroke 1997)
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Cost Effectiveness for rt-PA in Acute Ischemic
Stroke

• rt-PA placebo p value
• LOS 10.9 12.4 0.02
• Discharge home 48 36 0.002
• With rt-PA, considering 1,000 eligible patients
• Hospitalization costs 1.7 million more
• Rehabilitation costs 1.4 million less
• Nursing home costs 4.8 million less
• 564 quality-adjusted life-years saved

(Fagan, Neurology 1998)
Epidemiology
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STARS Study

• Prospective Phase IV study mandated by FDA
• Multicenter (24 academic, 33 community)
• NINDS protocol used for 389 patients
• Median times Onset to treatment 2.7
  hrs Arrival to treatment 1.6 hrs Less than 4
  treated in under 90 mins
• Median NIHSS 13 (14 mean)

(Albers, JAMA 2000)
Management
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STARS Study

• Results Outcome
• Favorable outcome 35 (mR?1)
• Functionally independent 43 (mR?2)
• 30 day mortality rate 13
• Results Complications
• Symptomatic ICH 3.3
• Within 3 days
• Fatal ICH 1.8

(Albers, JAMA 2000)
Management
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STARS Study

• Predictors of favorable outcome
• Baseline NIHSS lt 10
• Absence of significant CT abnormalities
• Age lt 85 years
• Lower mean arterial pressure
• Predictors of lack of response
• NIHSS (22 decrease in OR per 5 points)
• NIHSS gt 10 75 decrease in OR
• Significant CT findings 87 decrease in OR
• Increased mean arterial pressure 19 decrease in
  OR

(Albers, JAMA 2000)
Management
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Cleveland Area Experience

• Historical prospective cohort study
• Conducted July 1997 through June 1998
• Multicenter 29 hospitals (academic
  and community)
• No coordination or fixed protocol (NINDS
  protocol assumed)
• 3948 patients reviewed

(Katzen, JAMA 2000)
Management
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Cleveland Area Experience

• Results
• 3984 AIS patients admitted to 29 hospitals in 1
  yr
• 17 admitted within 3 hours of stroke onset
• 1.8 received t-PA at 16 hospitals (0 - 10.2
  of stroke patients)
• Of the top 4 hospitals in Cleveland, utilization
  ranged from 0-28 within 3 hour window

(Katzen, JAMA 2000)
Management
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Cleveland Area Experience

• Results Complications in tPA patients
• Total ICH rate 22
• Symptomatic ICH 15.7
• Fatal ICH 8.6
• Results Mortality rate
• tPA patients 15.7
• Patients in 3 hours ø tPA 7.2
• All patients ø tPA 5.1

(Katzen, JAMA 2000)
Management
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Cleveland Area Experience

• Results Protocol violations
• Total NINDS violations 50
• Antiplatelets / anticoagulants 37.1
• Beyond 3 hours 12.9 (3.15-6.25 hrs)
• Risk of complications not associated with
  protocol violations (p0.74)

(Katzen, JAMA 2000)
Management
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How to Evaluate and Treat Acute Ischemic Stroke
in 2000

Evaluation
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Acute Myocardial Infarction

• This paradigm has shifted
• Chest pain / SOB / dysrhythmia
• Rapid access to EMS
• Prehospital identification and call
• Prehospital ECG
• Team and protocols in place in ED
• Door to Drug - 30 Minutes
• What is the mortality and morbidity?

Evaluation
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2000 American Stroke AssociationNew Guidelines

• EMS systems should implement a stroke protocol
• Potential fibrinolytic candidates should be taken
  to hospitals capable of providing acute stroke
  care
• E.D. AIS triage should be similar to AMI
• Intravenous fibrinolysis for AIS is Class I
• Intra-arterial fibrinolysis for AIS is Class IIb

(ASA, Circulation 2000)
Evaluation
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Stroke Chain of Survival Recovery

• Detection Early recognition
• Dispatch Early EMS activation
• Delivery Transport management
• Door ED triage
• Data ED evaluation management
• Decision Specific therapies
• Drug Thrombolytic future agents

Evaluation
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NIH Symposium Recommendations

• 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

Evaluation
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Detection Stroke Public Awareness
Evaluation
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Dispatch Call 911Delivery Transport
Management

• Priority dispatch
• ABCs
• Time of onset
• Neurological evaluation / Prehospital stroke
  scale
• Check glucose
• Stroke recognition
• Early hospital notification
• Rapid Transport

Evaluation
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Door Emergent TriageData ED Evaluation
Evaluation
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Preparation

• Check glucose
• Two large IV lines
• Oxygen as needed
• Cardiac monitor
• Continuous pulse-ox
• Non-contrast CT scan
• ECG
• CXR

• Perform the NIH stroke scale
• Get rt-PA
• Prepare to mix
• Have pharmacy alerted
• Make sure family is available
• Contact primary care provider

Evaluation
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Preparation

• Systems and personnel need to be in place
• Know your Stroke Team before you need them!

Evaluation
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General Stroke Management

• Oxygen
• Use to correct hypoxia
• Suggestion it may hurt one year survival 69
  3L NC vs 73 control
• Glucose
• Maintain euglycemia
• Treat glucose lt 50 with D50
• Treat glucose gt 300 mg/dl with insulin

(Rønning, Stroke 1999)
Evaluation
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General Stroke Management

• Cardiac monitor
• Observe for ischemic changes or atrial
  fibrillation
• Intravenous fluids 
• Avoid D5W and excessive fluid administration
• IV normal saline at 50 cc / hr unless otherwise
  required
• NPO
• Aspiration risk is great, avoid oral intake until
  swallowing assessed
• Temperature
• Avoid hyperthermia, PO/PR acetaminophen prn

Evaluation
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The True Time of Onset

• Multiple sources
• How normal were they?
• Who saw them this morning?
• Clearly no symptoms?
• Times of reference
• The time the basketball game started

Evaluation
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Neurologic ExaminationNIH Stroke Scale

• Value of the NIHSS
• Correlates with size of stroke and prognosis
• Strokes with NIHSS lt 4 do well and are not
  typically thrombolytic candidates
• Strokes with NIHSS gt 20 are large with extremely
  poor prognosis and fair response to IV
  thrombolytics

Evaluation
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Middle Cerebral ArteryStroke Syndromes

• Dominant hemisphere
• Contralateral hemiparesis arm, face gt leg
• Contralateral sensory loss
• Contralateral homonymous hemianopia Ipsilateral
  eye deviation
• Brocas and Wernickes aphasias
• Non-dominant hemisphere
• Contralateral hemiparesis arm, face gt leg
• Contralateral sensory loss with extinction
• Contralateral homonymous hemianopia Ipsilateral
  eye deviation
• Dysarthria without aphasia
• Ipsilateral hemineglect, inattention, extinction
  on double stimulation

Evaluation
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Anterior and Posterior Cerebral Arteries Stroke
Syndromes

• Anterior Cerebral Artery
• Contralateral hemiparesis leg gt arm, face
• Contralateral sensory loss
• Change in personality, speech perserveration
• Bilateral occlusions produce paraplegia,
  anarthria, akinetic mutism
• Posterior Cerebral Artery
• Contralateral hemianopia (patients frequently
  unaware)
• Brain stem findings (varied)
• Bilateral occlusions produce cortical blindness

Evaluation
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Early CT Changes in Ischemic Stroke

• Loss of insular ribbon
• Loss of gray-white interface
• Loss of sulci
• Acute hypodensity
• Mass effect
• Dense MCA sign

Relative contraindication
Evaluation
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ConsiderationsWho will it and wont it help

• Factors associated with worse outcomes
• Increased patient age
• History of diabetes mellitus
• Increased time from onset
• Increased blood pressure
• Increased stroke severity
• Baseline CT findings of stroke
• All subgroups (age, race, gender, co-morbid
  illnesses, and stroke location and size)
  benefited from thrombolytics compared to placebo
  in the NINDS trial

Evaluation
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Factors Associated with Increased Risk of ICH

• Treatment initiated gt 3 hours
• Increased thrombolytic dose
• Elevated blood pressure
• NIHSS gt 20
• Acute hypodensity or mass effect on baseline CT

Evaluation
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Differential Diagnosis

• Intracerebral hemorrhage
• Hypoglycemia / Hyperglycemia
• Seizure
• Migraine headache
• Hypertensive crisis
• Epidural / subdural
• Tumor
• Meningitis / Encephalitis / Abscess

Evaluation
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Stroke Diagnosis - TIA

• TIA definition an arbitrary definition from
  1970s
• TIAs lasting longer than several minutes can
  produce focal defects on neuroimaging
• Median duration 14 mins / 8 mins
• If symptoms persist more than 1 hour, only 14
  resolved by 24 hours
• NINDS placebo group only had 2 improvement to
  baseline at 24 hours

(CSOTIA)
Evaluation
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Exclusions to Thrombolytics

• Stroke or head trauma in 3 mos
• Major surgery within 14 days
• Any history of intracranial hemorrhage
• SBP gt 185 mm Hg
• DBP gt 110 mm Hg
• Rapidly improving or minor symptoms
• Symptoms suggestive of subarachnoid hemorrhage
• Glucose lt 50 or gt 400 mg/dl

• GI hemorrhage within 21 days
• Urinary tract hemorrhage within 21 days
• Arterial puncture at non-compressible site past 7
  days
• Seizures at the onset of stroke
• Patients taking oral anticoagulants
• Heparin within 48 hours AND an elevated PTT
• PT gt15 sec
• Platelet count lt100 X 109/L

Evaluation
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Exclusions to Thrombolytics

• Patients were also excluded if aggressive
  measures were required to lower the blood
  pressure to within specified limits

Evaluation
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Blood Pressure Management

• Gentle management if thrombolytic
  candidate SBP gt 180 mm Hg DBP gt 110 mm Hg
• Choices
• Labetalol 10 - 20 mg IV
• Enalapril 1.25 mg IV
• Nitropaste 1 to chest wall
• No nipride or nitroglycerin gtts

Evaluation
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Blood Pressure Management

• Management in non-thrombolytic candidates only
  if SBP gt 220 mm Hg DBP gt 120 mm
  Hg MAP gt 130 mm Hg
• Also consider BP management in
• Acute myocardial infarction
• Aortic dissection
• True hypertensive encephalopathy
• Severe left ventricular failure

Evaluation
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What are the Options?

• No thrombolytics
• Nothing
• Aspirin
• Heparin
• Intravenous rt-PA Only approved therapy for
  acute stroke
• Other
• Intra-arterial thrombolysis
• Low dose IV rt-PA followed by IA rt-PA
• Investigation procedure

Treatment
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Stroke Treatment Aspirin / Heparinoids

• Aspirin
• Two large trials
• International Stroke Trial (IST)
• Chinese Acute Stroke Trial (CAST)
• Death / nonfatal strokes reduced 11
• If not a thrombolytic candidate, give within
  first 24 hrs
• Heparin
• Two important trials
• International Stroke Trial (IST)
• TOAST (Trial of ORG 10172)
• No net stroke benefit

Treatment
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rt-PA Dosing

• 0.9 mg/kg (max 90 mg)
• 10 bolus (over 1 minute)
• Remainder as a 1 hour infusion
• Have the rt-PA in the Emergency Department, not
  the Pharmacy!

Treatment
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Post-Treatment Care
Treatment
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Patient Monitoring

• ICU admission (24 hours)
• Neuro checks
• Q 15 minute X 6 hours
• Q 1 hour X 18 hours
• BP checks
• Call on the FIRST abnormal reading!
• Do not hesitate to use a drip
• Watch for bleeding

Treatment
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Contingency Plan - ICH Orders

• STAT Repeat CT
• STAT Labs
• (Fibrinogen, CBC, PT/PTT)
• Type and screen
• Cryoprecipitate / Platelets
• Neurosurgical consult

Treatment
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Blood Pressure ManagementAfter Thrombolytics

• SBP 180 - 230 or DBP 105-120 mm Hg
• Labetalol 10 mg IV, may repeat / double to 150 mg
  max
• Labetalol drip 2-8 mg / min
• SBP gt 230 or DBP 121 - 140 mm Hg
• Above
• Sodium nitroprusside
• DBP gt 140 mm Hg
• Sodium nitroprusside (0.5 µg/kg per minute)
• May consider enalapril in patients with CHF,
  asthma, abnormal cardiac conduction

Treatment
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Post-treatment Issues

• Management of seizures
• Management of increased ICP
• Risk factor identification and modification
• Swallowing assessment
• Early rehabilitation

Treatment
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The Future of Acute Stroke Treatment

• Establishment of tiered Stroke Centers
• New diagnostic tools Neuroimaging, markers
• Thrombolytics ProUK, TNK, rPA, ANCROD
• Intra-arterial approaches IA, stents,
  angioplasty
• Combination agents Antiplatelets, LMWH,
  neuroprotectives
• Cerebral protection Hypothermia, HBO
• Surgical Hemicraniectomy
• fibrinogenolytic

Future
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Primary Stroke Center Proposal

• 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

Individualized by institution Within 2 hours
(Brain Attack Coalition, JAMA 2000)
Future
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Intra-arterial Thrombolysis
Future
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Intra-Arterial Thrombolytic Efficacy vs.Time of
Delivery
EMS
GC/NK
PROACT
Control
(Ernst, Stroke 2000)
Future
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61 yo male with acute strokeThe Decision to
Treat

• 1435 IV rt-PA given. 0.9 mg/kg total 10
  bolus - 9 mg 90 over 1 hr - 81 mg
• 1545 Patient goes to ICU
• Report personally given to ICU staff
• 1550 Pathway actions begin
• (HOB, BP, aspiration precautions, carotid
  ultrasound)

Case
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61 year old male s/p rt-PA 24 Hour Follow-up

• Initial NIHSS 10
• 24 hr NIHSS 3
• Mild facial palsy
• Right arm drift
• Mild dysarthria
• Repeat CT shows areas of infarct

Case
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61 year old male s/p t-PAHospital Course

• Carotid U/S shows 60 -80 stenosis left ICA
• Speech recommends swallowing II diet and daily
  checks
• Physical therapy ongoing
• CEA performed day 4
• Patient discharged day 7

Case
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Conclusions

• Acute stroke is an emergency
• Multidisciplinary systems must be in place in
  every institution
• Strict adherence to protocols minimizes
  complications
• Acute stroke treatment is and will remain the
  responsibility of the Emergency Physician

Conclusion