acute stroke it’s not just t-pa the basics. nina t. gentile, md associate professor department of...

Acute StrokeAcute Stroke

It’s Not Just t-PA

The BasicsThe Basics

Nina T. Gentile, MDNina T. Gentile, MD

Associate Associate ProfessorProfessor

Department of Emergency Department of Emergency MedicineMedicine

Temple University Hospital Temple University Hospital & School of Medicine& School of Medicine

Philadelphia, PAPhiladelphia, PA

Nina T. Gentile, MD, FAAEM


Stroke BasicsStroke Basics

• How important is blood pressure control? • How do early ischemic changes on CT

impact on decision-making and treatment?

• What roles do aspirin and heparin play?• Is hyperglycemia really a problem?• What are the indications for immediate

transfer?


Case ExampleCase Example

• 72-year-old woman

• History: hypertension, diabetes

• Sudden slurred speech, left facial droop, left-sided weakness

• Family calls 911


Case ExampleCase Example

• ACLS squad dispatched, evaluates, transports patient to nearest ED

• En route the squad notifies the receiving hospital of a possible stroke patient

• And asks….

““Hey Doc… Hey Doc… How About Aspirin?”How About Aspirin?”

“Isn’t it…

…the sooner the better?”



Aspirin in Stroke Meta-AnalysisAspirin in Stroke Meta-Analysis

• 41,399 subjects • Nine trials• For every 1,000 patients…

…7 fewer early recurrent strokes …13 fewer dead or dependent at 6

months…~ 2 intracerebral bleeds


Aspirin Trials for StrokeAspirin Trials for Stroke

• International Stroke Trial (IST)

• Chinese Acute Stroke Trial (CAST)

• Treatment within 48 hours• IST time to treatment: 19 hours

• CAST time to treatment: 25 hours


International Stroke TrialInternational Stroke Trial

• 19,435 patients

• 300 mg/d aspirin within 48 hours of stroke onset

• Slightly fewer deaths at 14 days: 9.0% vs 9.44%, p=.02, NNT =91

2.8%3.9%

0.9%

0.8%

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

Aspirin Avoid Aspirin

HemorrhagicIschemic

IST – 14 DAY OUTCOME

p=.05

p=.05

36.5%38.8%

2022242628303234363840


Dead or Dependent

IST – 6 MONTH OUTCOME

p=.05


Chinese Acute Stroke TrialChinese Acute Stroke Trial

• 21,106 patients

• 160 mg/d dose within 48 hours of stroke onset

• Primary end points:

• Death at 4 weeks

• Death or dependence at discharge


3.3

1.6

3.9

2.1

0

1

2

3

4

5

6

7

8


Recurrent Stroke

4-wk Mortality

p=.01

p=.04


30.5% 31.6%

20

22

24

26

28

30

32

34

36


Dead or Dependent

p=.08


Aspirin in Acute Stroke: <6 HoursAspirin in Acute Stroke: <6 Hours

• Not studied ICH when used with lytic

• Early thrombolytic trials

• Phase IV trials


Thrombolysis: Early StudiesThrombolysis: Early Studies

• ASK (1996): SK or Placebo plus ASA within 4 hours of symptom onset

SK +ASA ASA

Mortality 36% 20%

HT or Hematoma

32% 17%


Thrombolysis: Early StudiesThrombolysis: Early Studies

• MAST- I (1995): within 6 hours of symptom onset• streptokinase,

• aspirin,

• both or

• neither


Thrombolysis: MAST-IThrombolysis: MAST-I

Therapy 10-Day Mortality Streptokinase 27%Aspirin 12%Both 34%*Neither 13%

*OR 3.5; 95% CI 1.9-6.5; 2p < 0.00001OR 3.5; 95% CI 1.9-6.5; 2p < 0.00001


Phase IV: IV t-PA in StrokePhase IV: IV t-PA in Stroke

The Cleveland Area Experience

• Symptomatic ICH: 15.7%

• Protocol violation: 50%• Received aspirin within 24 hours: 37%


Phase IV: IV t-PA in StrokePhase IV: IV t-PA in Stroke

STARS 2000• Symptomatic ICH: 3.3%• Asymptomatic ICH: 8.2% • Protocol violation in 33%

• rt-PA >180 minutes: 13%• Received aspirin or anticoagulant

within 24 hours: 9%


Aspirin in Acute StrokeAspirin in Acute Stroke

• Recommendation: 160 to 325 mg/day within 24 to 48 hours

• Avoid in potential candidates for thrombolytic therapy

• Delay for at least 24 hours after the administration of rt-PA

• Do not administer prehospital (i.e. pre-CT)


Our Patient Arrives…Our Patient Arrives…

• Right gaze preference

• Left face droop

• Dysarthria

• Left arm paresis

• Mild left side neglect


Three Questions…Three Questions…

• Is this a stroke?

• How would you quantify or describe the stroke?

• Would you give t-PA?


Differential DiagnosisDifferential Diagnosis

• Intracerebral hemorrhage

• Hypoglycemia

• Hyperglycemia

• Seizure

• Migraine headache

• Hypertensive crisis

• Tumor

• Meningitis

• Encephalitis

• Brain abscess


‘‘Misdiagnosis of Stroke’Misdiagnosis of Stroke’

• 821 patients admitted to acute stroke unit

• 108 (13%) incorrect diagnosis• Seizure: 39%

• Confusional states, syncope: 24%

Lancet. 1982 Feb 6;1(8267):328-31Lancet. 1982 Feb 6;1(8267):328-31


Stroke Mimics: Libman 1995Stroke Mimics: Libman 1995

• Evaluator: stroke team• Studies: history, physical• Misdiagnosis: 19%• Mimics identified: seizure, infection, tumor,

metabolic, positional vertigo, cardiac syncope, subdural, C- spine fracture, transient amnesia, conversion disorder, MS, myasthenia gravis, parkinsonism, hypertensive encephalopathy


Stroke Mimics: Kothari 1995Stroke Mimics: Kothari 1995

• Evaluator: emergency physician

• Studies: history, physical, CT

• Misdiagnosis: 4%

• Mimics identified: paresthesia, seizure, migraine, neuropathy, psychogenic, others


Stroke Mimics: Allder 1999Stroke Mimics: Allder 1999

• Evaluator: neurologist


• Misdiagnosis: 9%

• Mimics identified: metabolic, migraine, conversion disorder, withdrawal


Stroke Mimics: Ay 1999Stroke Mimics: Ay 1999

• Evaluator: neurologists


• Misdiagnosis: 1.2%

• Mimics identified: seizure, migraine, tumor, transient global amnesia


NIH Stroke Scale (NIHSS)NIH Stroke Scale (NIHSS)

• Designed as research tool

• Widely used in clinical practice

• Good interobserver reliability

• Helps predict outcome


NIH Stroke Scale (NIHSS)NIH Stroke Scale (NIHSS)

• Helps assess risk of hemorrhage after t-PA treatment

• Provides quantitative mechanism for following individual patient


Our Patient’s NIHSS Score (Part 1)Our Patient’s NIHSS Score (Part 1)

00-4Motor Arm Right6

30-4Motor Arm Left5

20-3Facial Palsy4

00-3Best Visual3

10-2Best Gaze2

10-2LOC Commands1c

10-2LOC Questions1b

10-3Level of

consciousness1a

Pt scoreRangeDescriptionItem


Our Patient’s NIHSS Score (Part 2)Our Patient’s NIHSS Score (Part 2)

00-3Best Language13

10-2Dysarthria12

10-2Neglect11

10-2Sensory10

00-2Limb Ataxia9

00-4Motor Leg Right8

10-4Motor Leg Left7

Pt scoreRangeDescriptionItem

Total = 13


Would you Give t-PA?Would you Give t-PA?

• Potential Benefit

• Potential Risks

• Exclusion Criteria• Historical features

• CT findings


IV t-PA: Potential BenefitIV t-PA: Potential Benefit

• 2775 patients in 6 trials

Odds of favorable 3-mo outcome

0-90 2.8 1.8-4.5

91-180 1.6 1.1-2.2

181-270 1.4 1.1-1.9

271-360 1.2 0.9-1.5

Lancet. 2004


IV t-PA for Stroke: Meta-analysisIV t-PA for Stroke: Meta-analysis

Stroke. 2005


Complete Resolution in 24 HoursComplete Resolution in 24 Hours

0

5

10

15

20

25

t-PA placebo

(NIHSS(NIHSS<<1)1)


NINDS 1 Year Follow-up NINDS 1 Year Follow-up

01020304050607080

<9 10-14 15-20 >20

t-PAPlacebo

Favo

rabl

e O

utco

me

Presenting NIHSS Score


IV t-PA: Potential RiskIV t-PA: Potential Risk

• Intracranial hemorrhage• Pooled analysis of 2775 patients

treated within 6 hours of sx onset

• rt-PA: 82 (5.9%)

• Placebo:15 (1.1%)


Clinical Exclusion CriteriaClinical Exclusion Criteria

Bleeding Risk• Active GI or GU

bleeding • Bleeding Diathesis

• PLT < 100K• INR > 1.7 PTT

• Potential Major Bleeding Site

BP sys>185, dias >110

• Stroke Mimic• BS < 50, > 400• Seizure at onset

• Rapidly improving or minor symptoms


CT Exclusion Criteria: Blood CT Exclusion Criteria: Blood


Early Ischemic ChangesEarly Ischemic Changes

• Loss of insular ribbon

• Loss of gray-white interface

• Loss of sulci • Acute hypo density • Mass effect • Dense MCA sign



Sylvian Fissure

Insular Cortex



• Loss of insular ribbon

• Loss of gray-white interface




• Loss of insular ribbon • Loss of gray-white

interface



• Loss of insular ribbon ()• Loss of gray-white

interface ()

• Loss of sulci ( )• Acute hypodensity • Mass effect • Dense MCA sign





interface • Loss of sulci

• Acute hypodensity

• Mass effect • Dense MCA sign




interface • Loss of sulci • Acute hypo density • Mass effect

• Dense MCA sign


“No hemorrhage…

…large area of hypoattenuation with edema….”

Would You Give t-PA to Our Patient?Would You Give t-PA to Our Patient?


Review the FactsReview the Facts


SignificanceSignificance

Early ischemic changes can…

…assist in decision-making

…predict outcome

…predict ICH


EIC Assists Decision-MakingEIC Assists Decision-Making

…findings change over time

…are correlated with perfusion deficits


EIC Predicts OutcomeEIC Predicts Outcome

43 patients, t-PA (30-100 mg)

PPV for death

• Hypodensity > 50% MCA: 85%

• Local brain swelling: 70%

• Hyperdense MCA: 32%

Amer J Neurorad 1994Amer J Neurorad 1994


EIC Predict OutcomeEIC Predict OutcomeFavors tPAFavors Placebo


EIC Predicts ICHEIC Predicts ICH

ECASS I• If >1/3 MCA involvement: increased

risk of bleed• OR 3.6, 95% CI, 2.3 to 5.3

NINDS• Only CT exclusion: hemorrhage• No association with EIC extent


What To Look For On CT What To Look For On CT

• Any signs of blood

• Hypodensity >1/3 MCA territory

• EICs difficult to appreciate • Should not dissuade use of

appropriate therapy

• Correlate with the history

Neurology Resident: Neurology Resident: “Oh no…she’ll be sure to bleed “Oh no…she’ll be sure to bleed

with t-PA….with t-PA….Let’s start Heparin instead.”Let’s start Heparin instead.”

We “have to do something”



Potential IndicationsPotential Indications

• Cardioembolic Stroke

• Progressing Stroke

• Stroke due to documented large-artery stenosis

• Arterial Dissection


IV AdministrationIV Administration

• 225 patients• IV Heparin vs Placebo for 7 days• No difference at 7 days, 3 mos, 1yr

• stroke progression • functional activity

• More patients in heparin group died at 1 year

Ann Intern Med. 1986 Dec;105(6):825-8


SubQ Heparin:IST

• 19,435 Patients

• 4 Groups: • ASA, Heparin 5,000U or 12,500U bid,

Both, or Neither

• 1o Outcome: • Death at 14 days

• Death or dependency at 6 mos


IST

9.0 9.3

5

6

7

8

9

10

Heparin Avoid Heparin

14-Mortality (NS)


IST

Heparin Avoid Heparin0

62.9 62.9

10203040506070

6-mo Dead/Dependent (NS)


IST: No Net BenefitIST: No Net Benefit

0

2.93.8

1.40.4

1

2

3

4

5


Ischemic Hemorrhagic


Immediate Use in Atrial Fibrillation Immediate Use in Atrial Fibrillation

0

1

2

3

4

5

6


2.8

4.9

Ischemic

2.1

0.4

Hemorrhagic


EUSI and AHA:EUSI and AHA:Heparin in StrokeHeparin in Stroke

1. No recommendation for general use of heparin, LMWH or heparinoids after

ischemic stroke (Level I)

2. Full dose heparin for selected indications such as AF, other cardiac sources with

high risk of re-embolism, arterial dissection, or high grade arterial stenosis (Level IV)

3. DVT-prophylaxis


What are the Options?What are the Options?

• Intravenous t-PA

• Excluded from Thrombolytics• Nothing

• Aspirin

• Heparin

• Intra-arterial thrombolysis


Neuroimaging Neuroimaging

• Assessment of blood flow and tissue viability• CT Angiography

• MRI with perfusion imaging


MRIMRI

Acute CBFDWI


72-yr-old Right MCA stroke72-yr-old Right MCA stroke• 5:05 Angiography reveals multiple thrombi

proximal MCA and segmental arteries• 5:25 Microangiocatheter IA t-PA

administration• 6:30 Patient goes to ICU


10-day T2

MRIMRI

Acute CBF DWI


72-yr-old S/P t-PA72-yr-old S/P t-PA

• Day 2: PT and speech therapy started

• Day 10: Hospital discharge to resume managing her brokerage company

Stroke Survivors.com


Case #2Case #2

• 43 year old black male with headache, right sided face, arm, leg weakness and vertigo x 30 minutes

• PMH: Hypertension, diabetes

• Exam: Dysarthria, profound weakness and ataxia


Initial Vital SignsInitial Vital Signs

• BP: 220/120 mm Hg

• Pulse: 64 regular

• Resp Rate: 24 regular

• Accucheck: 428 mg%


Severe HypertensionSevere Hypertension

• What is the optimal BP?

…with fibrinolytic therapy?

• When to initiate treatment?

• Which antihypertensive?


Severe HypertensionSevere Hypertension

• Worsens cerebral blood flow

• Decreases odds of full recovery

• Promotes hemorrhagic transformation and ICH after t-PA

Dutka, 1987

Chamorro,1998


OptOptimal BP imal BP

• No controlled studies to guide

• “Permissive hypertension”• Target BP in patients with prior

hypertension: 180 / 100-105 mmHg• Target BP in previously normotonic

patients: 160-180 / 90-100 mmHg

• Avoid hypotension, drastic reductions in BP


BP Management:BP Management:

• Systolic<220 or Diastolic<120• Observe

• Except with end-organ involvement (aortic dissection,AMI,pulmonary edema, hypertensive encephalopathy)

Not Eligible for Thrombolytic Therapy 1Not Eligible for Thrombolytic Therapy 1


• Systolic>220 or Diastolic 121–140Labetalol 10–20 mg IV; may repeat Q 10 min (max 300 mg) Nicardipine 5 mg/hr IV initial dose;

increase 2.5 mg/hr Q 5 min (max 15 mg/hr)

• Diastolic>140Nitroprusside 0.5 µg/kg/min IV infusion

initial dose, titrate

BP Management:BP Management:Not Eligible for Thrombolytic Therapy 2Not Eligible for Thrombolytic Therapy 2


• Systolic >185 or Diastolic >110Labetalol 10–20 mg IV over 1–2

min, may repeat x 1Nicardipine 5 mg/hr IV initial dose; increase 2.5 mg/hr Q 5 min (max 15 mg/hr)Nitropaste 1–2 inches

***If BP systolic>185 or diastolic>110, do not give r-TPA***

BP Management:BP Management:Pretreatment for Thrombolytic TherapyPretreatment for Thrombolytic Therapy


• Diastolic >140: Nitroprusside

0.5 µg/kg/min IV initial dose and titrate

• Systolic 180-230 or Diastolic 105–140:

- Labetalol bolus then drip at 2-8 mg/min

- Nicardipine 5 mg/hr IV initial dose,

2.5 mg/hr Q 5 min (max15 mg/hr)

BP Management:BP Management:During & After Thrombolytic TherapyDuring & After Thrombolytic Therapy


Induced HypertensionInduced Hypertension

• Phenylephrine or Norepinephrine can improve neurologic deficits

• IV NS, LR, or 10% hydroxyethyl starch 200/0.5 (HES) augments local perfusion to ischemic tissue

Rordorf, Stroke, 1997 Hillis, Cerebrovasc Dis, 2003

Aichner, 2003


Returning to our CaseReturning to our Case

• BP remains ~220/120 mm Hg

• Anticipating IV t-PA or with the possibility of ICH….

…..give Labetalol (10 mg bolus IV ) or Cardene by IV infusion if available

The Nurse Wants to KnowThe Nurse Wants to Know

What about the Blood Sugar?

Do you want to hang fluids?

Give Insulin?



Hyperglycemia in StrokeHyperglycemia in Stroke

• Accounts for 25 to 50% of patients

• Associated with worsened outcome• increases cerebral edema

• hemorrhagic transformation of ischemic strokes

• increases mortality with BS > 130mg%


Hyperglycemia after Stroke

<.0001Mortality

P

18 (7%)

High BS (>130 mg%)

n=259

6 (2%)

Normal BS (<130 mg%)

ICH <.000117 (7%)1 (2%)

<.0001Mortality 46 (52%)16 (15%)

Ischemic

Hemorrhagic

n=385

n=109 n=89


Hyperglycemia after Stroke

GLYCEMIC CONTROL

<.00011 (1.3%)18 (7%)Mortality.0152 (64%)161 (62%)D/C Home

PControlNo control

n=81Ischemic n= 259

<.0001 Mortality 15 (43%)24 (65%)

Hemorrhagic n=37 n=35

HypercoagulabilityHypercoagulability

0

50

100

150

200

250

0 200 400 600Blood Glucose

Fa

cto

r V

IIa

Blood Glucose Level vs Factor VIIa

r2 =.82, p<.001


HyperglycemiaHyperglycemia

• EUSI and AHA Recommendations:

- Treat hypoglycemia- Give Insulin for Blood Glucose >

300 mg%


InsulinInsulin

NEJM


Returning to our CaseReturning to our Case


43 yo with ICH43 yo with ICH

• Patient given 50 gm Mannitol

• Emergently intubated and ventilated to maintain pCO2 of 32 mmHg

• Given with 8 mg midazolam and 10 mg vecuronium

• Nurse wants to know if you’ll need a bed or will you be transferring the patient


Surgical Rx of ICH - 1Surgical Rx of ICH - 1

1. Large clots in the frontal, temporal or occipital regions with progressive clinical deterioration.



2. Deep basal ganglia clot in the non-dominant hemisphere with progressive deficit


3. Acute cerebellar hematoma larger than 3cm.


Nonsurgical Rx for ICHNonsurgical Rx for ICH

• Small bleeds or GCS >12

• No chance for recovery or GCS < 4


Returning to our caseReturning to our case

• Undergoes craniotomy and evacuation of hemorrhage with ventriculostomy placement

ED Presentation 24o p ED Presentation


43 yo s/p ICH Evacuation43 yo s/p ICH Evacuation

• Intermittently following commands with left arm, right-sided hemiparesis

• Discharged to extended care facility 24 days after admission

• Antihypertensive regimen• Clonidine• Minoxidil• Atenolol


30-day Stroke Mortality30-day Stroke Mortality

22%36%10%1996-00

19%48% 10%1981-88

OverallHemorrhagicICH or SAH

IschemicLacunar or

Cortical

Period


Disability Among Stroke SurvivorsDisability Among Stroke Survivors

Need Help caring for Themselves

Need Help Walking3120

71

01020304050607080

% Stroke Survivors

Impaired Vocational Capacity


Stroke Patients’ Views Stroke Patients’ Views on Stroke Outcomeon Stroke Outcome

• Elderly stroke patients with disability vs age-matched controls

• Preferred death to severe disability• 69% of stroke patients• 82% of controls

• Over 1/3 preferred painless death to even minor disability

Clin Rehab 2000; 14:417-424


Acute Stroke Care-Acute Stroke Care-It’s Not Just t-PAIt’s Not Just t-PA

• Aspirin should be avoided until after CT and the question of t-PA is answered

• Individualize BP management • Early ischemic changes on CT help with

decision-making• Heparin has no role (other than DVT

prophylaxis)• Intensify blood sugar management• Transfer: imaging, interventional neurorad, or

surgery

Stroke TeamStroke Team

Neuroradiology, Interventional

Neurology4 WEST4 WEST

Neurosurgery

EDED

Neuroradiology, Diagnostic

PHYSICAL MEDICINE and REHABILITATION

STAT LABSTAT LABNICUNICU

Neurovascular ResearchNeurovascular Research

http://medschool.temple.edu/Neurosurgery/index.html


StrokeStroke

Questions?? Questions??

[email protected]@ferne.org

Nina Gentile, MDNina Gentile, MD

[email protected] 215 707 8402

formatted_gentile_stroke_aaem_2005.ppt 2/11/2005 10:31 PMNina T. Gentile, MD, FAAEM

http://www.ferne.org/



acute stroke it’s not just t-pa the basics. nina t. gentile, md associate professor department of...

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