.1

Management of Ischemic Stroke

Somchai Towanabut MD.Somchai Towanabut MD.Prasat Neurological InstitutePrasat Neurological InstituteDepartment of Medical ServicesDepartment of Medical ServicesMinistry of Public HealthMinistry of Public Health

.2

Burden of stroke

STROKE: Epidemiology, Burden of disease

Global Disease Mortality 2002Global Disease Mortality 2002

World Health Organization. The World Health Report 2003: Shaping the Future. 2003.

0 5 10 15 20Mortality (millions)

Cardiovascular diseaseMalignant neoplasms

InjuriesRespiratory infections

COPD and asthmaHIV/AIDS

Perinatal conditionsDigestive diseases

Diarrhoeal diseasesTuberculosis

Childhood diseasesMalaria

Diabetes

10% of All Deaths Worldwide 10% of All Deaths Worldwide Are Due to StrokeAre Due to Stroke

HIV/AIDS=human immunodeficiency virus/acquired immunodeficiency syndrome.Adapted from World Health Organization. Global Burden of Stroke. 2005. Available at: www.cvd_atlas_16_death_from_stroke.pdf.

Other 27%

Cancer 12%

Stroke10%

Injury9%

Respiratory tractinfection 7%

HIV/AIDS 5%

Chronic obstructive pulmonary disease 5%

Perinatal causes

Diarrheal diseaseTuberculosis

3%3%4%

2%

Malaria

Coronary heart disease 13%

Stroke-Related Mortality Is Expected to Stroke-Related Mortality Is Expected to Continue to Increase Slightly Over TimeContinue to Increase Slightly Over Time

0

2

4

6

8

10

12

14

2010 2020 2030

All

Dea

ths

(%)

Men

Women

Adapted from Reinhardt E. The Atlas of Heart Disease and Stroke. UN Chronicle Online Edition. 2005. Available at: http://www.looksmarttrends.com/p/articles/mi_m1309/is_1_42/ai_n14695955.

Year

WORLD HEALTH ORGANIZATION

The WHO Stroke Surveillance System

Facts:• Stroke is to a large extent preventable, but

prevention relies on good epidemiologic data• Two-thirds of all stroke deaths occur among people

in developing countries • Stroke will be among the five most important

causes of disability in both developing and developed countries

.7

Burden of stroke in Thailand

STROKE: Epidemiology, Burden of disease

อั�ตราตายอั�ตราตาย/ / แสนประชากรด้�วยโรคหลอัด้เล�อัด้สมอังแสนประชากรด้�วยโรคหลอัด้เล�อัด้สมอัง ((I60- I60- I69)I69) ป�ป� - 2537 254- 2537 25477

9.64 9.85 8.98 8.516.26

1012.42

17.3219.85

29.0631.09

0

5

10

15

20

25

30

35

40

2537 2538 2539 2540 2541 2542 2543 2544 2545 2546 2547

ส�าน�กระบาด้ว�ทยา กรมควบค มโรคส�าน�กระบาด้ว�ทยา กรมควบค มโรค, http://epid.moph.go.th/, http://epid.moph.go.th/

Proportion of ill-define deathsProportion of ill-define deaths

0 0.1 0.2 0.3 0.4 0.5 0.6

Thailand

El savador

Egyp

Ecuador

Guatamala

Portugal

France

World Health Organization. the WHO Mortality Database 1999 Geneva, 1999

The top ten killers in Thailand 1999 (Males)The top ten killers in Thailand 1999 (Males)

Diseases Deaths %

1. HIV/AIDS 40,064 18

2. Traffic accidents 21,901 10

3. Stroke 18,286 8

4. Liver cancer 13,774 6

5. COPD 10,977 5

6. Ischemic heart disease 9,734 4

7. Homicide/violence 6,786 3

8. Suicides 6,671 3

9. Lung cancer 6,461 3

10. Diabetes 6,223 3

Burden of disease and injuries in Thailand: Ministry of Public Health Nov 2002 (http://203.157.19.191/index-burden.htm)

The top ten killers in Thailand 1999 (FemalesThe top ten killers in Thailand 1999 (Females))

Diseases Deaths %

1. Stroke 23,433 14

2. HIV/AIDS 16,443 10

3. Diabetes 12,235 7

4. Ischemic heart disease 8,089 5

5. Liver cancer 7,938 5

6. Lower respiratory tract infection 5,521 3

7. Traffic accident 5,330 3

8. COPD 5,132 3

9. Tuberculosis 4,413 3

10. Nephritis&Nephrosis 4,123 2

Burden of disease and injuries in Thailand: Minstry of Public Health Nov 2002 (http://203.157.19.191/index-burden.htm)

Top ten cause of disease burden (DALYS) in Thailand 1999 (male)Top ten cause of disease burden (DALYS) in Thailand 1999 (male)

Disease DALYs %

1. HIV/ AIDS 960,086 172. Traffic accident 510,909 93. Stroke 271,009 54. Liver cancer 248,083

45. Diabetes 168,594 36. Ischemic heart disease 159,188 37. COPD 156,861 38. Homocide/ violence 156,853 39. Suisides 147,988 310. Drug dependency 137,703 2 Burden of disease and injuries in Thailand:

Minstry of Public Health Nov 2002 (http://203.157.19.191/index-burden.htm)

Disease DALYs %

1. HIV/ AIDS 372,956 102. Stroke 282,509 73. Diabetes 267,155 74. Depression 145,336 45. Liver cancer 118,384

36. Osteoarthritis 117,994

37. Anemia 112,990 38. Traffic accident 108,449 39. Ischemic heart disease 102,863 310. Cataracts 96,091 2 Burden of disease and injuries in Thailand:

Minstry of Public Health Nov 2002 (http://203.157.19.191/index-burden.htm)

Top ten cause of disease burden (DALYS) in Thailand 1999 (female)Top ten cause of disease burden (DALYS) in Thailand 1999 (female)

Preliminary data from TES studyPreliminary data from TES study

• Crude prevalence (age 45- 80 years) ~ 1.9 %

• Crude incidence (age 45- 80 years) ~ not less than 261/ 100,000/ year

15

Mortality 25% within a year, 15-30% permanently disable. (The most common cause of long-term disability in the elderly.)

DISEASE BURDEN

THAILAND USA WORLD

1 POPULATION 65 M. 250 M. 6,500 M.

2 NEW CASES/YEAR 100,000 – 150,000

600,000 –

750,000

20 M.

3 HEMORRHAGE 30% 15% 25%

4 ISCHEMIC STROKE

65 – 75% 85% 75%

5 MORTALITY 40,000 150,000 5.5

16

IN THAILAND

- 150,000 NEW CASES/YEAR

COST OF CARE

- 2,500 - 25,000 USD/CASE

(NOT INCLUDE THE INCOME LOSS)

SOCIAL IMPACT

50,000-80,000 PEOPLE CAN BE

SAVE(COST 125 - 200 MILLION USD/YEAR)

THE CONTINUUM OF STROKE CARE

PRIMARY PREVENTION

Stroke Unit. & Acute care

Investigation

Rehabilitation and

recovery

TIME

ACUTE STROKE

Secondary prevention

Stroke free population DEATH

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Management of Ischemic Stroke

Management of Ischemic Stroke

Management Management iischemic strokeschemic stroke• Diagnosis & differential diagnosis

• General supportive care

• Acute treatment

• Treatment of neurological complication

• Secondary prevention

Management Management iischemic strokeschemic stroke• Diagnosis & differential diagnosis

• General supportive care

• Acute treatment

• Treatment of neurological complication

• Secondary prevention

Ischemic strokeIschemic strokeDiagnosis & differential diagnosis

• Sudden onset, focal deficit, risk factors

• Brain imaging

• Cardiac test

• Blood tests ( blood sugar, BUN, Cr, electrolytes, etc.)

Brain imaging • CT should be done in all case• May be except in lacunar syndromes

- Pure motor hemiparesis- Pure sensory stroke- Motor sensory stroke- Ataxic hemiparesis- Dysarthria clumsy hand syndrome

Ischemic strokeIschemic stroke

Ischemic strokeIschemic strokeGeneral supportive care

• Airway, Breathing, Circulation

• Fever

• Hypertension

• IV fluid

• Treatment of underlying diseases

HypertensionHypertension• DBP > 140 mmHg X 2 5 min apart

Sodium nitroprusside 0.25-10 µg/ kg/ min IV

Nitroglycerine 5 mg IV and 1-4 mg/ h

• SBP > 220 mmHg, DBP 120-140 mmHg X 2 20 min apart Captopril 6.25-12.5 mg oralNitroglycerine patchHydralazine 5-10mg IV

• Do not use Nifedipine sublingual

HypertensionHypertension• SBP 185-220 mmHg or DBP 105-120 mmHg

Do not use antihypertensive drug except

- Left ventricular failure- Aortic dissection- Acute myocardial infarction- Acute renal failure- Hypertensive

encephalopathy

Management Management iischemic strokeschemic stroke• Diagnosis & differential diagnosis

• General supportive care

• Acute treatment• Treatment of neurological complication

• Secondary prevention

Ischemic strokeIschemic strokeAcute treatment • Recanalization

IV rt-PA (Intravenous thrombolysis )

IA r-proUK (FDA?)• Neuroprotective treatment• Aspirin in first 48 hours• Anticoagulant• Hemodilution• Therapeutic hypothermia• Stroke unit

Intravenous Intravenous thrombolysisthrombolysis• FDA approved 1996 based on NINDS rt- PA Stroke

Study• Treatment within 3 hours of symptom onset• Complete neurological improvement or

improvement >= 4 points on NIHSS at 24 hours

• Complete or nearly complete recovery at 3 months• Symptomatic brain hemorrhage is major risk (6.4%

VS 0.6%)• But mortality rate was similar

3 months (17% VS 20%)1 year (24% VS 28%)

Intravenous Intravenous thrombolysisthrombolysis

• Presence of brain edema, mass effect associated with hemorrhage

• NIHSS < 20, age < 75 years had greatest possibility for good outcome

• NIHSS >22 had very poor prognosis whether or not rt-PA

• Low attenuation > 1/ 3 of MCA territory less likely to had good outcome

• Good response were highest among patients with NIHSS <10normal baseline CT

Patients with ischemic stroke who Patients with ischemic stroke who could be treated with rt-PAcould be treated with rt-PA

1. Measurable neurological deficit

2. Signs should not be clearing spontaneously

3. Signs should not be minor and isolated

4. Caution should be exercised with patient with major deficits

5. Symptoms should not be suggestive of SAH

6. Onset of symptoms < 3 hours before start of treatment

Patients with ischemic stroke who Patients with ischemic stroke who could be treated with rt-PAcould be treated with rt-PA

7. No head trauma or prior stroke in previous 3 months

8. No MI in previous 3 months

9. No GI or urinary tract hemorrhage in previous 21 days

10.No major surgery in previous 14 days

11.No arterial puncture at non compressible site previous 7 days

12.No history of intracranial hemorrhage

Patients with ischemic stroke who Patients with ischemic stroke who could be treated with rt-PAcould be treated with rt-PA

13.BP not elevated (systolic < 185 and diastolic <110)

14.No evidence of active bleeding or acute trauma on examination

15.Not taking anticoagulant, or INR <= 1.5

16. If received heparin in previous 48 hours, aPTT must be normal

17.Platelet >= 100,000/ mm3

18.Blood glucose >= 50 mg%, <= 400 mg%

Patients with ischemic stroke who Patients with ischemic stroke who could be treated with rt-PAcould be treated with rt-PA

19.No seizure with postictal deficit

20.CT dose not show a multilobar infarction( hypodensity > 1/ 3 cerebral hemisphere )

21.Patient or family understand the potential risks and benefits of treatment

Regimens for iv rt-PA Regimens for iv rt-PA treatmenttreatment• Infusion 0.9 mg/ kg (max 90 mg) over 1 hour,

10 % bolus dose over 1 minute

• Admit to ICU or stroke unit

• Neurological assessments every 15 minutesduring infusion

every 30 minutes next 6 hours

every hours until 24 hours

• If severe headache, acute hypertension, nausea, vomiting, discontinue infusion, and emergency CT brain

Regimens for iv rt-PA Regimens for iv rt-PA treatmenttreatment• Measure BP every 15 minutes for first 2 hours

every 30 minutes for next 6 hoursevery 1 hours until 24 hours

• If systolic BP >=180 mmHg or diastolic BP >=105 mmHg,

increase frequency of BP measurement, administer antihypertensive drug to maintain BP at or below this levels

• If diastolic BP >140 mmHg, sodium nitroprusside 0.5mg/ kg/ min

Regimens for iv rt-PA Regimens for iv rt-PA treatmenttreatment• Delayed placement of NG tube, bladder

catheters, intra- arterial catheters

• Anticoagulants and antiplatelet agents should be delayed for 24 hours after treatment

• Staffs, CT, Neurosurgeon, Laboratory test available 24 hours

• Cryoprecipitate or fresh frozen plasma, platelet concentration

Ischemic strokeIschemic stroke

Aspirin (mg)Aspirin (mg)

EUSI * ASA † RCOP (London) ‡

Acute treatment 100-300 160-300 300

2nd prevention 50-325 50-300

* European Stroke Initiative Executive Committee( EUSI ). 2003 † American Stroke Association ( ASA ). 2003‡ Royal College of Physician of London. 2004

Stroke unitStroke unit• Stroke patient should be treated in

stroke unit (level I)• Reduced mortality and handicap

17% reduction in death7% increase in being able to

live at home8% reduction in length of stay

• Provide a co-ordinate multidisciplinary approach to treatment and care

Stroke unitStroke unit• Consists of a hospital unit or a part of

hospital unit • Provide a co-ordinate multidisciplinary care• Team should have specialist interest in

stroke management, work in co-ordinate way (through regular meeting)

• Admission, discharge criteria, care protocol, outcome data should be provided

• Programme of regular staff education and training should be provided

Stroke unitStroke unitTypical components of care• Assessment

• Early management (early mobilization, prevention of complications, treatment of metabolic derangement)

• Rehabilitation

Stroke unitStroke unit• Various forms of stroke unit exist

1. Acute stroke unit ( continuing treatment < 1 wk )

2. Comprehensive stroke unit

3. Rehabilitation stroke unit (after delay of 1-2 wks)

4. A mobile stroke team• Optimal size of stroke unit is not known• Small hospital comprehensive unit

Large hospital acute + rehabilitation

Stroke unitStroke unit• Well defined geographic area

• Multidisciplinary team approach with regular meeting

• Treatment protocol: CPG, care map, clinical pathway

• Evaluation

Ischemic strokeIschemic strokeTreatment

Effects measured in trials

IV r-tPA 10 63 ASA 3 12Stroke unit 9 56

#avoiding#avoidingdeath ordeath or

dependency/dependency/10001000

relative risk relative risk reduction (%)reduction (%)

Hankey G, Warlow C. Lancet 1999; 354: 1457- 63

AnticoagulantAnticoagulant• Routine anticoagulant is not

recommended in acute ischemic stroke (A)

• Not recommend in moderate- severe stroke (A)

• Not recommend within 24 h. in patient with r-tPA

• Used only hemorrhage has been excluded by imaging

American stroke association 2003

AnticoagulantAnticoagulantPossible remaining indications for heparin

treatment after stroke• Cardioembolic with high risk of re-embolism

(artificial valve, AF,MI with mural thrombi, left atrial thrombosis )

• Symptomatic dissection of extracranial arteries• Symptomatic extracranial and intracranial stenoses

a. Symptomatic ICS prior to operationb. Crescendo TIAs or stroke in progression

• Sinus- venous thrombosis• Coagulopathy such as protein C and S deficiency

European Stroke Initiative Executive Committee and the EUSI Writing committee 2003

AnticoagulantAnticoagulantContraindications• Large infarction• Uncontrollable arterial

hypertension• Advanced microvascular

changes in the brain

*European Stroke Initiative Executive Committee and the EUSI Writing committee 2003

Management Management iischemic strokeschemic stroke• Diagnosis & differential diagnosis

• General supportive care

• Acute treatment

• Treatment of neurological complication• Secondary prevention

Treatment of Treatment of neurological neurological complicationcomplication• Cerebral edema and increased

intracranial pressure

• Seizures

• Hemorrhagic transformation

Cerebral edema and Cerebral edema and increased intracranial increased intracranial pressurepressure• Elevated head of the bed 20- 30 degrees• Avoid “Jugular vein” compression• Consider osmotherapy

20% Mannital 0.25-0.5 g / Kg IV in 20 mins 4-6 times / dayor 10% Glycerol 250 ml IV in 30-60mins 4 time / dayor 50% Glycerol50 ml oral 4 time / dayand / or

Furosemide 1 mg / Kg IV

Cerebral edema and Cerebral edema and increased intracranial increased intracranial pressurepressure• Avoid hypotonic solution

• Avoid hypoxia, consider intubation

• Hyperventilationkeep pCO2 30-35 mmHg

• Avoid steroid

Treatment of Treatment of neurological neurological complicationcomplication• Cerebral edema and increased

intracranial pressure

• Seizures

• Hemorrhagic transformation

Management Management iischemic strokeschemic stroke• Diagnosis & differential diagnosis

• General supportive care

• Acute treatment

• Treatment of neurological complication

• Secondary prevention

Risk of Recurrent Cardiovascular Risk of Recurrent Cardiovascular Events Is HighEvents Is High

0

5

10

15

20

30 Days 1 Year 5 Years

Recurrent stroke

MI = myocardial infarction.

Adapted from Dhamoon MS et al. Presented at the 57th Annual Meeting of the American Academy of Neurology; Miami Beach, FL. April 9-16, 2005. S38.005.

MI or fatal cardiac event

Follow-up Timepoint

Pat

ien

ts W

ith

Eve

nt

(%)

(n=655)

Secondary preventionSecondary preventionAntiplatelet• There are 3 treatment options

Aspirin 50-325 mg OD

Clopidogrel 75 mg OD

Aspirin 50 mg + dipyridamole 200 mg twice daily

Secondary preventionSecondary preventionAnticoagulant• Cardioembolic stroke

INR 2-3• Should not be used in non cardioembolic

stroke

Control risk factors• HT, DM, Smoking, Hyperlipidemia, Life

style, Stress, Obesity

Secondary preventionSecondary preventionCarotid endarterectomy• CEA is indicated for patient with stenosis 70-99 %

valid only for center with perioperative complication < 6 % (level I)

• CEA may be indicated for patient with stenosis 50-69 %valid only for center with perioperative complication < 6 % (level III)

• CEA is not recommended for patient with stenosis < 50 %

Secondary preventionSecondary prevention

Extracranial-Intracranial Anastomosis• Is not benificial in preventing stroke in patient

with MCA or ICA stenosis or occlusion

Carotid Angioplasty and stenting• May be indicated for patient with

contraindication to CEA or with stenosis at surgical inaccessible sites

• May be indicated for patient with re-stenosis after CEA orstenosis following radiation

Management Management iischemic strokeschemic stroke• Diagnosis & differential diagnosis

• General supportive care

• Acute treatment

• Treatment of neurological complication

• Secondary prevention

http://www.pni.go.th

ConclusionsConclusions

• Stroke is a major health problem in Thailand

• Stroke unit, r-tPA are the major advances

• To improve the quality of care :Multidisciplinary/ network

approach CQI activities are very importance