THROMBOLYSIS IN ACUTE ISCHEMIC STROKE

Experience at our stroke unit in 2011-2012

DR Sanjay Jaiswal, D.M DR Sanjay Jaiswal, D.M Member World Stroke OrganizationMember World Stroke Organization

Senior Consultant Neurologist &Senior Consultant Neurologist &Stroke NeurophysicianStroke Neurophysician

Jaiswal Hospital and Neuro Institute, Jaiswal Hospital and Neuro Institute, KOTAKOTA

Outlines Outlines The burden of disease & Stroke FactsThe burden of disease & Stroke Facts Pathophysiology Pathophysiology Stroke mimicsStroke mimics Pre thrombolysis work up.Pre thrombolysis work up. Safety and efficacy of IV Safety and efficacy of IV t PA .t PA . Inclusion and Exclusion criteria's.Inclusion and Exclusion criteria's. How Tpa is administered. How Tpa is administered. Time frame (Door to needle time)Time frame (Door to needle time) Our stroke teamOur stroke team

THE BURDEN OF STROKE

Anually more than 15 million people Anually more than 15 million people world wide suffer a stroke, 5.5 million world wide suffer a stroke, 5.5 million die and 5 million are left with permanent die and 5 million are left with permanent disability.disability.

Stroke is 2nd most common cause of Stroke is 2nd most common cause of death.death.

In India 1.5million people suffer from In India 1.5million people suffer from Acute Stroke every year.Acute Stroke every year.

1880 people die every day in 1880 people die every day in India due to strokeIndia due to stroke

World wide some one dies of stroke World wide some one dies of stroke every 6 seconds.every 6 seconds.

Every two second some one some Every two second some one some where in world suffers from stroke.where in world suffers from stroke.

Stroke kills more people each year Stroke kills more people each year than AIDS, TB, and Malaria put than AIDS, TB, and Malaria put together.together.

Incidence of stroke is increasing in Incidence of stroke is increasing in India and other developing India and other developing countriescountries

Stroke Facts

80 % of strokes are 80 % of strokes are Ischemic . Ischemic .

Only 15 % of stroke patients Only 15 % of stroke patients reach in hospital within 3 reach in hospital within 3 hrs.hrs.

1-5% are thrombolysed1-5% are thrombolysed

Reasons for lack of thrombolysis

1. Patient’s inability to recognize stroke symptoms.

40% of stroke patients can’t name a single 40% of stroke patients can’t name a single symptom of stroke.symptom of stroke.

85% of patients believe that their symptoms 85% of patients believe that their symptoms are not serious enough to seek urgent are not serious enough to seek urgent treatment.treatment.

2. Physician’s lack of experience with stroke thrombolysis and therefore reluctance to “risk” treatment

3. Lack of organized delivery of care in most of the

medical centers throughout the country.

Nandigram et al 2003

Observed lack of knowledge Observed lack of knowledge regarding stroke thrombolysis regarding stroke thrombolysis among medical professionals in among medical professionals in india.india.

Significant majority of the GPs were Significant majority of the GPs were not aware of the beneficial effects of not aware of the beneficial effects of thrombolysis.thrombolysis.

CASE 1CASE 1 76 Yr old Retired Head Master, relative of a 76 Yr old Retired Head Master, relative of a

doctor.doctor.

No H/O HTN, DM,CADNo H/O HTN, DM,CAD

Presented with H/O Acute onset Rt hemiparesis Presented with H/O Acute onset Rt hemiparesis

with difficulty in walking independently at 6.30 with difficulty in walking independently at 6.30

PM ,was brought on wheel chair.PM ,was brought on wheel chair.

Reached to our hospital at 7.50 PM.Reached to our hospital at 7.50 PM.

CT head –No e/o hemorrhage ,haematological CT head –No e/o hemorrhage ,haematological

invest done. Clinical work up completed. by invest done. Clinical work up completed. by

9.00 PM.9.00 PM.

Consent received at 10 .00 PM ( 1 hour Consent received at 10 .00 PM ( 1 hour

wasted by relatives in giving consent )wasted by relatives in giving consent )

Thrombolysis started at 10.00 PMThrombolysis started at 10.00 PM

Motor power started improving during Motor power started improving during

thrombolysis.thrombolysis.

In 24 hrs pt was able to walk with little In 24 hrs pt was able to walk with little

support.support.

Discharged on 6 day with mild Neurodeficit.Discharged on 6 day with mild Neurodeficit.

A doctor who is relative of the patient played A doctor who is relative of the patient played

important role in explaining beneficial important role in explaining beneficial

effects of thrombolysiseffects of thrombolysis

CASE 2 76 Yr old male F/O a Doctor had stroke.76 Yr old male F/O a Doctor had stroke. At 8.30 AM had left sided weakness with slurred At 8.30 AM had left sided weakness with slurred

speech and confused state ,not able to walk.speech and confused state ,not able to walk.

Brought into hospital at 9.30 AM. Brought into hospital at 9.30 AM.

Pt wheeled straight into CT scan.Pt wheeled straight into CT scan.

Pt shifted to stroke unit, IV Line started and blood Pt shifted to stroke unit, IV Line started and blood

withdrawn.withdrawn.

k/c HT, CAD, H/O Angioplasty 15 yrs ago, on k/c HT, CAD, H/O Angioplasty 15 yrs ago, on

anti HT + ASAanti HT + ASA.(missed ASA for 2 days).(missed ASA for 2 days)

Lt UL– Lifting against gravity but weak Lt UL– Lifting against gravity but weak grip.grip.

Lt LL –2- /5, not able to walk Lt LL –2- /5, not able to walk independentlyindependently

Poor comprehension with dysarthriaPoor comprehension with dysarthria CT--. No hemorrhage seenCT--. No hemorrhage seen BP---140/80BP---140/80 RBS– 118 MG%, CBC, PT , APTT- Normal.RBS– 118 MG%, CBC, PT , APTT- Normal. Option of thrombolysis given to his son.Option of thrombolysis given to his son. Consent for tPA taken.Consent for tPA taken.

IV tPA started at 11.30 am. (stroke to needle IV tPA started at 11.30 am. (stroke to needle

time 3 hrs)time 3 hrs) By the time infusion was finished , pt By the time infusion was finished , pt

became alert and his motor power improved became alert and his motor power improved

significantly.significantly. By evening (6 hrs post thrombolysis) pt. was By evening (6 hrs post thrombolysis) pt. was

walking independently and and had normal walking independently and and had normal

speech.speech. Discharged on 3Discharged on 3rdrd day with no neurodeficit, day with no neurodeficit,

WITH COMPLETE RECOVERY.WITH COMPLETE RECOVERY.

CASE 3CASE 3 68 Yr old male, 68 Yr old male,

k/c HT, CAD, h/o CABG 10 yrs ago, on anti HT + k/c HT, CAD, h/o CABG 10 yrs ago, on anti HT +

ASA.ASA.

At 9.30 PM had right sided weakness with slurred At 9.30 PM had right sided weakness with slurred

speech . speech .

Rt L/L Power 1-2 /5, Rt UL 3/5, dysarthria+Rt L/L Power 1-2 /5, Rt UL 3/5, dysarthria+

Brought into hospital at 11.00 PM.Brought into hospital at 11.00 PM.

Pt shifted to stroke unit, IV Line started and blood Pt shifted to stroke unit, IV Line started and blood

withdrawn.withdrawn.

CT scan head showed no e/o haemorrhage.CT scan head showed no e/o haemorrhage.

Consent for tPA takenConsent for tPA taken

IV- tPA started at 12.30 AM. (stroke to needle time 3 hrs.

During the infusion pt started moving Rt leg. and his grip had improved significantly.

By next morning (6 hrs post thrombolysis) pt was walking independantly and with no dysarthria.

Patient discharged without any neurodeficit.

PathophysiologyPathophysiology

2 Million Neurones are lost every minute in the period in which stroke is untreated

PathophysiologyPathophysiology ischemic penumbraischemic penumbra is the area of the is the area of the

brain surrounding the infarcted brain surrounding the infarcted core,and is preserved by a tenacious core,and is preserved by a tenacious supply of blood from collateral supply of blood from collateral vessels.vessels.

This area can be rescued if the This area can be rescued if the occluded vessel can be reopened occluded vessel can be reopened up to 3-8 hours from symptom up to 3-8 hours from symptom onsetonset

Cerebral infarct <3hrsCerebral infarct <3hrs

Onset

Infarct

Ischaemic penumbra

Cerebral infarct 6hrsCerebral infarct 6hrs

Infarct

Ischaemic penumbra

Cerebral infarct 24hrsCerebral infarct 24hrs

Infarct

Ischaemic penumbra

        Penumbrae of Ischemic Stroke

Penumbrae is the target of any reperfusion therapy

The fate of brain tissue depends on Time Cerebral blood flow

Occluded arterial flow Collateral blood flow

Time is brain-We have to act fast to rescue the Penumbrae

Stroke MimicsStroke Mimics SyncopeSyncope Partial epileptic Partial epileptic

seizure with Todd’s seizure with Todd’s paresisparesis

Migraine attack Migraine attack (aura)(aura)

HypoglycaemiaHypoglycaemia HysteriaHysteria IntoxicationIntoxication Hypertensive Hypertensive

encephalopathyencephalopathy

Subarachnoid Subarachnoid haemorrhagehaemorrhage

NeuroinfectionNeuroinfection NeoplasmNeoplasm Chr SDHChr SDH Multiple sclerosisMultiple sclerosis Peripheral vertigoPeripheral vertigo

Hyperacute Stroke: Modern Approach of Tt

Aim: Revascularization of penumbra Aim: Revascularization of penumbra Break down Clot!Break down Clot!

Methods: IV, IA, Mechanical Methods: IV, IA, Mechanical ThrombolysisThrombolysis

Most practical, with proven efficacy at Most practical, with proven efficacy at place like KOTA : IV thrombolysis with place like KOTA : IV thrombolysis with TPA. TPA.

Time is BrainTime is Brain

Pre thrombolysis work Pre thrombolysis work upup

Should be individualized Should be individualized All Pts must have emergently : All Pts must have emergently :

1.1. NCCT BRAIN NCCT BRAIN

2.2. ECGECG

3.3. CBC,Plat count, B groupCBC,Plat count, B group

4.4. B GlucoseB Glucose

5.5. Coagulation-PT with INR,APTTCoagulation-PT with INR,APTT

6.6. Other metabolic tests-RFT, LFT, etcOther metabolic tests-RFT, LFT, etc

NCCT BRAIN Initial imaging modality in hyper ac stroke Widely available, quick, easy to perform Accurately identifies ICH,SAH

EARLY SIGNS OF CEREBRAL ISCHAEMIA Hyper dense MCA artery sign Hyper dense dot sign Hypo density of insular ribbon Hypoensity of basal ganglia loss of grey white matter differentiation in

cortical ribbon sulcal effacement EARLY SIGNS ARE ASSOCIATED WITH POORER

OUTCOMES

Left and middle: Hyperdense left MCA sign (yellow arrow), hypoattenuated left basal

ganglia (red arrow), and cortical swelling (blue arrows) in the same patient. Right:

Dot sign (yellow arrow) in the left sylvian fissure.

Early CT signs in acute MCA Early CT signs in acute MCA stroke stroke

NIHSS SCORE NIHSS SCORE NIHSS SCORING CAN BE NIHSS SCORING CAN BE

PERFORMED IN 7 MINUTES . PERFORMED IN 7 MINUTES .

ESSENTIAL TO BE CALCULATED ESSENTIAL TO BE CALCULATED PREDICTOR OF STROKE OUTCOME AND PREDICTOR OF STROKE OUTCOME AND

USED AS A EXCLUSION CRITERIA USED AS A EXCLUSION CRITERIA ..

Inclusion CriteriaInclusion Criteria

Clinical signs and symptoms Clinical signs and symptoms consistent with stroke.consistent with stroke.

Patient last seen normal within 4.5 Patient last seen normal within 4.5 hrs.hrs.

Measurable neurological deficit.Measurable neurological deficit.

Exclusion Criteria Any hemorrhage on neuroimaging.Any hemorrhage on neuroimaging. Symptoms s/o SAH.Symptoms s/o SAH. Seizure at stroke onset with post ictal neurol Seizure at stroke onset with post ictal neurol

deficit.deficit. Hypodensity greater than 1/3 cerebral Hypodensity greater than 1/3 cerebral

hemisphere on CT.hemisphere on CT. SBP>185 & DBP>110SBP>185 & DBP>110 RBS <50 or > 400 mg%RBS <50 or > 400 mg% Stroke with major neurol deficits-NIHS >22.Stroke with major neurol deficits-NIHS >22. Minor/isolated/spontaneously clearing neurol Minor/isolated/spontaneously clearing neurol

signs.signs.

Exclusion Criteria Platelet count <1 lac/mm3Platelet count <1 lac/mm3 INR>1.7INR>1.7 Elevated APTT.Elevated APTT. Past h/o ICHPast h/o ICH Arterial puncture at non compressible Arterial puncture at non compressible

site in 7 days.site in 7 days. Major surgery in past 14 days.Major surgery in past 14 days. GI bleed or hematuria in past 21 days.GI bleed or hematuria in past 21 days. Ischemic stroke, Myocardial infarction or Ischemic stroke, Myocardial infarction or

serious head trauma in last 3 months.serious head trauma in last 3 months. Evidence of active bleeding or ac trauma Evidence of active bleeding or ac trauma

(fracture on exam).(fracture on exam).

Stroke Thrombolysis at 3-4.5 Hrs additional Exclusion

Criterias

Age >80 yearsAge >80 years On oral anticoagulants On oral anticoagulants

regardless of INRregardless of INR NIHSS of >25 (Severe stroke)NIHSS of >25 (Severe stroke) History of both stroke and History of both stroke and

diabetes. diabetes.

I.V I.V t PAt PA : : Safety and Safety and efficacy efficacy Evidence for Evidence for

tPA < 3 HourstPA < 3 Hours

NINDS t PA stroke trial(1995)

NEJM 95:333,1581-87NEJM 95:333,1581-87624 patients randomized624 patients randomized3 hour window3 hour windowAt three months 30% At three months 30% more likely to have more likely to have minimal or no disabilityminimal or no disability

6.4% risk of hemorrhage6.4% risk of hemorrhage

NINDS tPA Stroke Trial

0

10

20

30

0

10

20

30

tPA tPAPlacebo Placebo

31

20 9

8

20

1

NIHSS Excellent Recovery (%)

Total Death Rate (%)

Hemorrhagep < .05

New England Journal, 1995

NINDS TPA Stroke Trial

Global outcome statistic: OR=1.7, 50% v. 38%= 12% benefit

Excellent outcome at 3 months on all scales

52%

38%43%

26%

45%

31%34%

21%

0%

10%

20%

30%

40%

50%

60%

BarthelIndex

RankinScale

GlasgowOutcome

NIHSSscore

TPA

Placebo

N Engl J Med 1995;333:1581-7

Time is brain( EARLIER THE BETTER) benefit from rt-PA declines with increasing delay from onset to

treatment time

Benefit

Harm

3 hours 6 hours

Upper and lower 95% confidence limits

Line of no effect

IST-3 protocol

For every 100 patients treated with For every 100 patients treated with t t PA PA , ,

32 benefit, 3 harmed32 benefit, 3 harmed

Saver JL et al , Stroke 2007; 38:2279-2283

better outcome by 1 or more grades on the mRS

Stroke Thrombolysis:

Thrombolytic therapy must be Thrombolytic therapy must be given by an experienced given by an experienced physician physician after the imaging of after the imaging of the brain is assessed by the brain is assessed by physicians experienced in physicians experienced in reading the imaging studyreading the imaging study22

1: Hacke W et al.: Lancet (2004) 363:768-742: Wahlgren N et al.: Lancet (2007) 369:275-82

Stroke Stroke Thrombolysis: Thrombolysis:

Evidence for Evidence for t PAt PA at at 3 – 4.5 hrs3 – 4.5 hrs

Time is Brain :Time is Brain : NINDS Recommended Stroke NINDS Recommended Stroke Evaluation Targets for Potential Evaluation Targets for Potential

Thrombolytic CandidatesThrombolytic Candidates

Target time framesTarget time frames

Door to doctorDoor to doctor 10 minutes10 minutes

Door to CT completionDoor to CT completion 25 minutes25 minutes

Door to CT readingDoor to CT reading 45 minutes45 minutes

Door to drug treatmentDoor to drug treatment 60 minutes60 minutes

How to administer IV t PA

Infuse 0.9mg/kg(max 90 mg ) over 60 mnts Infuse 0.9mg/kg(max 90 mg ) over 60 mnts with 10 % of the dose given as bolus over 1 with 10 % of the dose given as bolus over 1 mnt.mnt.

Admit pt in neuro ICU or stroke unit.Admit pt in neuro ICU or stroke unit. Perform neurological assessment every 15 Perform neurological assessment every 15

mnts during the infusion and every 30 mnts mnts during the infusion and every 30 mnts thereafter for next 6 hours then hourly until thereafter for next 6 hours then hourly until 24 hours after treatment.24 hours after treatment.

If pt develop severe headache,ac HTN, If pt develop severe headache,ac HTN, nausea,or vomitting discontinue infusion and nausea,or vomitting discontinue infusion and obtain emergency CT scan.obtain emergency CT scan.

AngioedemaAngioedema

Risk of hemorrhagic transformation

Marked hyperglycemia Marked hyperglycemia

or DMor DM

CT >1/3 CT >1/3 cerebral cerebral

hemisphere hemisphere

Increasing stroke Increasing stroke

severityseverity

Low platelet countsLow platelet counts

~ Circulation. 2002~ Circulation. 2002

Higher NIHSS scoreHigher NIHSS score

Longer time to Longer time to

recanalizationrecanalization

~ Stroke. 2002~ Stroke. 2002

If intracranial hemorrhage present:

Obtain fibrinogen results. Obtain fibrinogen results. Prepare for administration of 6 to 8 units of Prepare for administration of 6 to 8 units of

cryoprecipitate containing factor VIII. cryoprecipitate containing factor VIII. Prepare for administration of 6 to 8 units of Prepare for administration of 6 to 8 units of

platelets.platelets. Consider alerting and consulting a hematologist Consider alerting and consulting a hematologist

or neurosurgeon. or neurosurgeon. Consider decision regarding further medical Consider decision regarding further medical

and/or surgical therapy. and/or surgical therapy. Consider second CT to assess progression of Consider second CT to assess progression of

intracranial hemorrhage. intracranial hemorrhage. A plan for access to emergent neurosurgical A plan for access to emergent neurosurgical

consultation is highly recommended.consultation is highly recommended.

Acute Ischemic Stroke Protocol

ER arrival

Triage nurse confirm stroke onset time < 4.5 hours

ER Resident performsRapid evaluation (5 minutes)1.exact time of onset2.important history3.quick neurological evaluationSTAT CT and blood work

Neurology Resident receivesER stroke page andproceeds to ERbrief history & physical exam Page Stroke consultant

Head CT findings, laboratory data, NIH stroke scaleConfirm the criteria fulfilling thrombolytic therapy for ischemic strokeFamily’s agreement for thrombolytic therapy

Stroke onset < 4.5 hoursIV-tPA treatment

Patient is admitted to Stroke ICU for intensive monitoring/care

Stroke onset 4.5-8 hoursIA t therapy /device

Call NeuroradiologistsIA thrombolysis/device

11STST Case tPA given in 3.30 hrs. Case tPA given in 3.30 hrs. 22ndnd Case tPA given in 3 hrs. Case tPA given in 3 hrs. 33rdrd Case tPA given in 3 hrs Case tPA given in 3 hrs All made excellent recovery.All made excellent recovery. Earlier protocol ---Earlier protocol ---

window period -- 3hrs.window period -- 3hrs. Latest ECASS 3 trial---Latest ECASS 3 trial---

window period extended upto window period extended upto 4.5 hrs.4.5 hrs.

OUR STROKE TEAM

NeurologistNeurologist NeurosurgeonNeurosurgeon IntensivistIntensivist NeuroradiologistNeuroradiologist NeuropathologistNeuropathologist NeurophysiotherepistNeurophysiotherepist RMOS,Techs,Trained staffRMOS,Techs,Trained staff

TAKE HOME MESSAGE

IV r TPA IS RECOMMENDED IV r TPA IS RECOMMENDED

THEREPY FOR SELECTED THEREPY FOR SELECTED

PATIENTS WHO REACH PATIENTS WHO REACH

HOSPITAL WITHIN 4.5 HOURS HOSPITAL WITHIN 4.5 HOURS

OF STROKE ONSET. OF STROKE ONSET. Thrombolysis is possible in kota.Thrombolysis is possible in kota.

Need to rush from bed to bedside.Need to rush from bed to bedside.

TAKE HOME MESSAGETAKE HOME MESSAGE

At 3 months 30% more likely to have At 3 months 30% more likely to have minimal or no disability following minimal or no disability following thrombolysis.thrombolysis.

There should be no protocol violation There should be no protocol violation other wise more complications.other wise more complications.

We have to increase awareness among We have to increase awareness among patients, general public and doctors patients, general public and doctors regarding beneficial effects of stroke regarding beneficial effects of stroke thrombolysis.thrombolysis.

World Stroke day- 29 octoberWorld Stroke day- 29 october

WSO Slogan- entitled WSO Slogan- entitled ‘Because I care..‘Because I care..

Because I care…I want you to know the facts about stroke

I want you to learn how to prevent the assault of stroke I will break the myths surrounding stroke, e.g., “stroke only happens later in

life”

I want you to have access to the best possible treatment

I will ensure that you receive quality treatment, care and support

I will be with you every step of the way towards your full recovery

THANK YOUTHANK YOU