THROMBOLYSIS IN ACUTE
ISCHEMIC STROKE
Experience at our stroke unit in
2011-2012
DR Sanjay Jaiswal, D.MDR Sanjay Jaiswal, ...
OutlinesOutlines
 The burden of disease & Stroke FactsThe burden of disease & Stroke Facts
 PathophysiologyPathophysiolo...
THE BURDEN OF STROKE
 Anually more than 15 million people world wideAnually more than 15 million people world wide
suffer...
 World wide some one dies of stroke every 6World wide some one dies of stroke every 6
seconds.seconds.
 Every two second...
Stroke Facts
 80 % of strokes are Ischemic .80 % of strokes are Ischemic .
 Only 15 % of stroke patients reach inOnly 15...
Reasons for lack of thrombolysis
1. Patient’s inability to recognize stroke symptoms.
 40% of stroke patients can’t name ...
Nandigram et al 2003
 Observed lack of knowledge regarding strokeObserved lack of knowledge regarding stroke
thrombolysis...
CASE 1CASE 1
 76 Yr old Retired Head Master, relative of a doctor.76 Yr old Retired Head Master, relative of a doctor.
 ...
 Consent received at 10 .00 PM ( 1 hour wasted byConsent received at 10 .00 PM ( 1 hour wasted by
relatives in giving con...
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 weakne...
 Lt UL– Lifting against gravity but weak grip.Lt UL– Lifting against gravity but weak grip.
 Lt LL –2- /5, not able to w...
 IV tPA started at 11.30 am. (stroke to needle time 3 hrs)IV tPA started at 11.30 am. (stroke to needle time 3 hrs)
 By ...
CASE 3CASE 3
 68 Yr old male,68 Yr old male,
 k/c HT, CAD, h/o CABG 10 yrs ago, on anti HT + ASA.k/c HT, CAD, h/o CABG 1...
 IV- tPA started at 12.30 AM. (stroke to needle
time 3 hrs.
 During the infusion pt started moving Rt leg.
and his grip ...
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 brainis the area of the brain
surro...
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
 ...
Stroke MimicsStroke Mimics
 SyncopeSyncope
 Partial epileptic seizurePartial epileptic seizure
with Todd’s paresiswith T...
Hyperacute Stroke: Modern
Approach of Tt
 Aim: Revascularization of penumbraAim: Revascularization of penumbra 
Break d...
Time is BrainTime is Brain
Pre thrombolysis work upPre thrombolysis work up
 Should be individualizedShould be individualized
 All Pts must have em...
NCCT BRAIN
 Initial imaging modality in hyper ac stroke
 Widely available, quick, easy to perform
 Accurately identifie...
Left and middle: Hyperdense left MCA sign (yellow arrow), hypoattenuated left basal
ganglia (red arrow), and cortical swel...
NIHSS SCORENIHSS SCORE
 NIHSS SCORING CAN BE PERFORMEDNIHSS SCORING CAN BE PERFORMED
IN 7 MINUTES .IN 7 MINUTES .
 ESSEN...
Inclusion CriteriaInclusion Criteria
 Clinical signs and symptoms consistent withClinical signs and symptoms consistent w...
Exclusion Criteria
 Any hemorrhage on neuroimaging.Any hemorrhage on neuroimaging.
 Symptoms s/o SAH.Symptoms s/o SAH.
...
Exclusion Criteria
 Platelet count <1 lac/mm3Platelet count <1 lac/mm3
 INR>1.7INR>1.7
 Elevated APTT.Elevated APTT.
 ...
Stroke Thrombolysis at 3-4.5 Hrs
additional Exclusion Criterias
 Age >80 yearsAge >80 years
 On oral anticoagulants rega...
I.VI.V t PAt PA :: Safety and efficacySafety and efficacy
Evidence for tPA < 3Evidence for tPA < 3
HoursHours
NINDS t PA stroke trial(1995)
 NEJM 95:333,1581-87NEJM 95:333,1581-87
 624 patients randomized624 patients randomized
 ...
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 Deat...
NINDS TPA Stroke Trial
Global outcome statistic: OR=1.7, 50% v. 38%= 12% benefit
Excellent outcome at 3 months on all scal...
Time is brain( EARLIER THE BETTER) benefit from rt-
PA declines with increasing delay from onset to
treatment time
Benefit...
For every 100 patients treated withFor every 100 patients treated with t PAt PA ,,
32 benefit, 3 harmed32 benefit, 3 harme...
Stroke Thrombolysis:
Thrombolytic therapy must be given byThrombolytic therapy must be given by
an experienced physicianan...
Stroke Thrombolysis:Stroke Thrombolysis:
Evidence forEvidence for t PAt PA at 3 – 4.5at 3 – 4.5
hrshrs
Time is Brain :Time is Brain : NINDS Recommended Stroke EvaluationNINDS Recommended Stroke Evaluation
Targets for Potentia...
How to administer IV t PA
 Infuse 0.9mg/kg(max 90 mg ) over 60 mnts with 10 % ofInfuse 0.9mg/kg(max 90 mg ) over 60 mnts ...
Risk of hemorrhagic
transformation
 MarkedMarked
hyperglycemia orhyperglycemia or
DMDM
 CT >1/3CT >1/3 cerebralcerebral
...
If intracranial hemorrhage present:
 Obtain fibrinogen results.Obtain fibrinogen results.
 Prepare for administration of...
Acute Ischemic Stroke Protocol
ER arrival
Triage nurse confirm stroke onset time < 4.5 hours
ER Resident performs
Rapid ev...
 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.
...
OUR STROKE TEAM
 NeurologistNeurologist
 NeurosurgeonNeurosurgeon
 IntensivistIntensivist
 NeuroradiologistNeuroradiol...
TAKE HOME MESSAGE
 IV r TPA IS RECOMMENDEDIV r TPA IS RECOMMENDED
THEREPY FOR SELECTED PATIENTSTHEREPY FOR SELECTED PATIE...
TAKE HOME MESSAGETAKE HOME MESSAGE
 At 3 months 30% more likely to have minimalAt 3 months 30% more likely to have minima...
World Stroke day- 29 octoberWorld Stroke day- 29 october
WSO Slogan- entitled ‘Because I care..WSO Slogan- entitled ‘Becau...
THANK YOUTHANK YOU
Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India
Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India
Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India
Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India
Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India
Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India
Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India
Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India
Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India
Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India
Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India
Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India
Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India
Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India
Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India
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Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India

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We are presenting our personal experience regarding thrombolytic therepy in ac ischaemic stroke patients at jaiswal hospital and neuro institute ,kota,Rajasthan,INDIA

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  • ER Procedure: Differential Diagnosis In stroke patients, clinical features are usually sufficient to enable at least preliminary diagnosis. CT scanning is instrumental in documenting cerebral haemorrhage, neuroinfection or brain injury, but does not help to exclude possibilities such as syncope, partial epileptic seizure with Todd’s paresis, migraine attack with aura, hypoglycaemia, hysteria, intoxication, meningitis or multiple sclerosis. In this context, it is important to remain aware that confirmatory tests should supplement – rather than replace – conventional clinical skills. In practice, the most important distinction is between ischaemic stroke and intracranial haemorrhage. The clinical features of these conditions may overlap, but their treatment is markedly different. 1 Early distinction between the various subtypes of ischaemic stroke is also becoming important (i.e. lacunar vs large artery or cardioembolic stroke), as there is evidence that these may respond differently to different treatments. This is a situation in which neuroimaging techniques such as CT scanning can be invaluable, although clinical scoring systems based on the presence or absence of specific clinical features can also be strongly predictive. One such system – the Allen score – has been found to be 90% accurate in the identification of haemorrhage. 2–4 References 1. European Ad Hoc Consensus Group. European strategies for early intervention in stroke: a report of an Ad Hoc Consensus Group meeting. Cerebrovasc Dis 1996; 6: 315–24. 2. Allen CMC. Clinical diagnosis of the acute stroke syndrome. Q J Med 1984; 208: 515–23. 3. Sandercock PAG, Allen CMC, Corston RN et al. Clinical diagnosis of intracranial haemorrhage using Guy’s hospital score. Br Med J 1985; 291: 1675–7. 4. Celani MG, Righetti E, Migliacci R et al. Comparability and validity of two clinical scores in the early differential diagnosis of acute stroke. Br Med J 1994 ; 308: 1674–6 27
  • Stroke thrombolysis Dr Sanjay Jaiswal,consultant nerologist,Jaiswal Hospital and neuro institute,kota,Rajasthan,India

    1. 1. THROMBOLYSIS IN ACUTE ISCHEMIC STROKE Experience at our stroke unit in 2011-2012 DR Sanjay Jaiswal, D.MDR 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, KOTAJaiswal Hospital and Neuro Institute, KOTA
    2. 2. OutlinesOutlines  The burden of disease & Stroke FactsThe burden of disease & Stroke Facts  PathophysiologyPathophysiology  Stroke mimicsStroke mimics  Pre thrombolysis work up.Pre thrombolysis work up.  Safety and efficacy of IVSafety 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
    3. 3. THE BURDEN OF STROKE  Anually more than 15 million people world wideAnually more than 15 million people world wide suffer a stroke, 5.5 million die and 5 million are leftsuffer a stroke, 5.5 million die and 5 million are left with permanent disability.with permanent disability.  Stroke is 2nd most common cause of death.Stroke is 2nd most common cause of death.  In India 1.5million people suffer from Acute StrokeIn India 1.5million people suffer from Acute Stroke every year.every year.  1880 people die every day in India due to1880 people die every day in India due to strokestroke
    4. 4.  World wide some one dies of stroke every 6World wide some one dies of stroke every 6 seconds.seconds.  Every two second some one some where inEvery two second some one some where in world suffers from stroke.world suffers from stroke.  Stroke kills more people each year than AIDS,Stroke kills more people each year than AIDS, TB, and Malaria put together.TB, and Malaria put together.  Incidence of stroke is increasing in India andIncidence of stroke is increasing in India and other developing countriesother developing countries
    5. 5. Stroke Facts  80 % of strokes are Ischemic .80 % of strokes are Ischemic .  Only 15 % of stroke patients reach inOnly 15 % of stroke patients reach in hospital within 3 hrs.hospital within 3 hrs.  1-5% are thrombolysed1-5% are thrombolysed
    6. 6. Reasons for lack of thrombolysis 1. Patient’s inability to recognize stroke symptoms.  40% of stroke patients can’t name a single symptom40% of stroke patients can’t name a single symptom of stroke.of stroke.  85% of patients believe that their symptoms are not85% of patients believe that their symptoms are not serious enough to seek urgent treatment.serious enough to seek urgent 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.
    7. 7. Nandigram et al 2003  Observed lack of knowledge regarding strokeObserved lack of knowledge regarding stroke thrombolysis among medical professionals inthrombolysis among medical professionals in india.india.  Significant majority of the GPs were not awareSignificant majority of the GPs were not aware of the beneficial effects of thrombolysis.of the beneficial effects of thrombolysis.
    8. 8. CASE 1CASE 1  76 Yr old Retired Head Master, relative of a doctor.76 Yr old Retired Head Master, relative of a doctor.  No H/O HTN, DM,CADNo H/O HTN, DM,CAD  Presented with H/O Acute onset Rt hemiparesis withPresented with H/O Acute onset Rt hemiparesis with difficulty in walking independently at 6.30 PM ,wasdifficulty in walking independently at 6.30 PM ,was brought on wheel chair.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 investCT head –No e/o hemorrhage ,haematological invest done. Clinical work up completed. by 9.00 PM.done. Clinical work up completed. by 9.00 PM.
    9. 9.  Consent received at 10 .00 PM ( 1 hour wasted byConsent received at 10 .00 PM ( 1 hour wasted by relatives in giving consent )relatives in giving consent )  Thrombolysis started at 10.00 PMThrombolysis started at 10.00 PM  Motor power started improving during thrombolysis.Motor power started improving during thrombolysis.  In 24 hrs pt was able to walk with little support.In 24 hrs pt was able to walk with little support.  Discharged on 6 day with mild Neurodeficit.Discharged on 6 day with mild Neurodeficit.  A doctor who is relative of the patient playedA doctor who is relative of the patient played important role in explaining beneficial effects ofimportant role in explaining beneficial effects of thrombolysisthrombolysis
    10. 10. 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 speech and confusedAt 8.30 AM had left sided weakness with slurred speech and confused state ,not able to walk.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 withdrawn.Pt shifted to stroke unit, IV Line started and blood withdrawn.  k/c HT, CAD, H/O Angioplasty 15 yrs ago, on anti HT +k/c HT, CAD, H/O Angioplasty 15 yrs ago, on anti HT + ASAASA.(missed ASA for 2 days).(missed ASA for 2 days)
    11. 11.  Lt UL– Lifting against gravity but weak grip.Lt UL– Lifting against gravity but weak grip.  Lt LL –2- /5, not able to walk independentlyLt LL –2- /5, not able to walk independently  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.
    12. 12.  IV tPA started at 11.30 am. (stroke to needle time 3 hrs)IV tPA started at 11.30 am. (stroke to needle time 3 hrs)  By the time infusion was finished , pt became alert and hisBy the time infusion was finished , pt became alert and his motor power improved significantly.motor power improved significantly.  By evening (6 hrs post thrombolysis) pt. was walkingBy evening (6 hrs post thrombolysis) pt. was walking independently and and had normal speech.independently and and had normal speech.  Discharged on 3Discharged on 3rdrd day with no neurodeficit, WITHday with no neurodeficit, WITH COMPLETE RECOVERY.COMPLETE RECOVERY.
    13. 13. CASE 3CASE 3  68 Yr old male,68 Yr old male,  k/c HT, CAD, h/o CABG 10 yrs ago, on anti HT + ASA.k/c HT, CAD, h/o CABG 10 yrs ago, on anti HT + ASA.  At 9.30 PM had right sided weakness with slurred speech .At 9.30 PM had right sided weakness with slurred 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 withdrawn.Pt shifted to stroke unit, IV Line started and blood withdrawn.  CT scan head showed no e/o haemorrhage.CT scan head showed no e/o haemorrhage.  Consent for tPA takenConsent for tPA taken
    14. 14.  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.
    15. 15. PathophysiologyPathophysiology 2 Million Neurones are lost every minute in the period in which stroke is untreated
    16. 16. PathophysiologyPathophysiology  ischemic penumbraischemic penumbra is the area of the brainis the area of the brain surrounding the infarcted core,and is preservedsurrounding the infarcted core,and is preserved by a tenacious supply of blood from collateralby a tenacious supply of blood from collateral vessels.vessels.  This area can be rescued if the occludedThis area can be rescued if the occluded vessel can be reopened up to 3-8 hours fromvessel can be reopened up to 3-8 hours from symptom onsetsymptom onset
    17. 17. Cerebral infarct <3hrsCerebral infarct <3hrs Onset Infarct Ischaemic penumbra
    18. 18. Cerebral infarct 6hrsCerebral infarct 6hrs Infarct Ischaemic penumbra
    19. 19. Cerebral infarct 24hrsCerebral infarct 24hrs Infarct Ischaemic penumbra
    20. 20. 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
    21. 21. Stroke MimicsStroke Mimics  SyncopeSyncope  Partial epileptic seizurePartial epileptic seizure with Todd’s paresiswith Todd’s paresis  Migraine attack (aura)Migraine attack (aura)  HypoglycaemiaHypoglycaemia  HysteriaHysteria  IntoxicationIntoxication  HypertensiveHypertensive encephalopathyencephalopathy  SubarachnoidSubarachnoid haemorrhagehaemorrhage  NeuroinfectionNeuroinfection  NeoplasmNeoplasm  Chr SDHChr SDH  Multiple sclerosisMultiple sclerosis  Peripheral vertigoPeripheral vertigo
    22. 22. Hyperacute Stroke: Modern Approach of Tt  Aim: Revascularization of penumbraAim: Revascularization of penumbra  Break down Clot!Break down Clot!  Methods: IV, IA, MechanicalMethods: IV, IA, Mechanical ThrombolysisThrombolysis  Most practical, with proven efficacy atMost practical, with proven efficacy at place like KOTA : IV thrombolysis withplace like KOTA : IV thrombolysis with TPA.TPA.
    23. 23. Time is BrainTime is Brain
    24. 24. Pre thrombolysis work upPre thrombolysis work up  Should be individualizedShould be individualized  All Pts must have emergently :All Pts must have emergently : 1.1. NCCT BRAINNCCT 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
    25. 25. 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
    26. 26. 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 MCAEarly CT signs in acute MCA strokestroke
    27. 27. NIHSS SCORENIHSS SCORE  NIHSS SCORING CAN BE PERFORMEDNIHSS SCORING CAN BE PERFORMED IN 7 MINUTES .IN 7 MINUTES .  ESSENTIAL TO BE CALCULATEDESSENTIAL TO BE CALCULATED PREDICTOR OF STROKE OUTCOME ANDPREDICTOR OF STROKE OUTCOME AND USED AS A EXCLUSION CRITERIAUSED AS A EXCLUSION CRITERIA ..
    28. 28. Inclusion CriteriaInclusion Criteria  Clinical signs and symptoms consistent withClinical signs and symptoms consistent with stroke.stroke.  Patient last seen normal within 4.5 hrs.Patient last seen normal within 4.5 hrs.  Measurable neurological deficit.Measurable neurological deficit.
    29. 29. 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 deficit.Seizure at stroke onset with post ictal neurol deficit.  Hypodensity greater than 1/3 cerebral hemisphere onHypodensity greater than 1/3 cerebral hemisphere on CT.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 signs.Minor/isolated/spontaneously clearing neurol signs.
    30. 30. 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 site in 7 days.Arterial puncture at non compressible 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 serious headIschemic stroke, Myocardial infarction or serious head trauma in last 3 months.trauma in last 3 months.  Evidence of active bleeding or ac trauma (fracture onEvidence of active bleeding or ac trauma (fracture on exam).exam).
    31. 31. Stroke Thrombolysis at 3-4.5 Hrs additional Exclusion Criterias  Age >80 yearsAge >80 years  On oral anticoagulants regardless of INROn oral anticoagulants regardless of INR  NIHSS of >25 (Severe stroke)NIHSS of >25 (Severe stroke)  History of both stroke and diabetes.History of both stroke and diabetes.
    32. 32. I.VI.V t PAt PA :: Safety and efficacySafety and efficacy Evidence for tPA < 3Evidence for tPA < 3 HoursHours
    33. 33. NINDS t PA stroke trial(1995)  NEJM 95:333,1581-87NEJM 95:333,1581-87  624 patients randomized624 patients randomized  3 hour window3 hour window At three months 30% more likelyAt three months 30% more likely to have minimal or no disabilityto have minimal or no disability  6.4% risk of hemorrhage6.4% risk of hemorrhage
    34. 34. 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 (%) Hemorrhage p < .05 New England Journal, 1995
    35. 35. 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% Barthel Index Rankin Scale Glasgow Outcome NIHSS score TPA Placebo N Engl J Med 1995;333:1581-7
    36. 36. 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
    37. 37. For every 100 patients treated withFor every 100 patients treated with t PAt 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
    38. 38. Stroke Thrombolysis: Thrombolytic therapy must be given byThrombolytic therapy must be given by an experienced physicianan experienced physician after theafter the imaging of the brain is assessed byimaging of the brain is assessed by physicians experienced in reading thephysicians experienced in reading the imaging studyimaging study22 1: Hacke W et al.: Lancet (2004) 363:768-74 2: Wahlgren N et al.: Lancet (2007) 369:275-82
    39. 39. Stroke Thrombolysis:Stroke Thrombolysis: Evidence forEvidence for t PAt PA at 3 – 4.5at 3 – 4.5 hrshrs
    40. 40. Time is Brain :Time is Brain : NINDS Recommended Stroke EvaluationNINDS Recommended Stroke Evaluation Targets for Potential Thrombolytic CandidatesTargets for Potential Thrombolytic 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
    41. 41. How to administer IV t PA  Infuse 0.9mg/kg(max 90 mg ) over 60 mnts with 10 % ofInfuse 0.9mg/kg(max 90 mg ) over 60 mnts with 10 % of the dose given as bolus over 1 mnt.the dose given as bolus over 1 mnt.  Admit pt in neuro ICU or stroke unit.Admit pt in neuro ICU or stroke unit.  Perform neurological assessment every 15 mnts duringPerform neurological assessment every 15 mnts during the infusion and every 30 mnts thereafter for next 6 hoursthe infusion and every 30 mnts thereafter for next 6 hours then hourly until 24 hours after treatment.then hourly until 24 hours after treatment.  If pt develop severe headache,ac HTN, nausea,orIf pt develop severe headache,ac HTN, nausea,or vomitting discontinue infusion and obtain emergency CTvomitting discontinue infusion and obtain emergency CT scan.scan.  AngioedemaAngioedema
    42. 42. Risk of hemorrhagic transformation  MarkedMarked hyperglycemia orhyperglycemia or DMDM  CT >1/3CT >1/3 cerebralcerebral hemispherehemisphere  Increasing strokeIncreasing stroke severityseverity  Low platelet countsLow platelet counts  Higher NIHSS scoreHigher NIHSS score  Longer time toLonger time to recanalizationrecanalization ~ Stroke. 2002~ Stroke. 2002
    43. 43. If intracranial hemorrhage present:  Obtain fibrinogen results.Obtain fibrinogen results.  Prepare for administration of 6 to 8 units of cryoprecipitatePrepare for administration of 6 to 8 units of cryoprecipitate containing factor VIII.containing factor VIII.  Prepare for administration of 6 to 8 units of platelets.Prepare for administration of 6 to 8 units of platelets.  Consider alerting and consulting a hematologist orConsider alerting and consulting a hematologist or neurosurgeon.neurosurgeon.  Consider decision regarding further medical and/or surgicalConsider decision regarding further medical and/or surgical therapy.therapy.  Consider second CT to assess progression of intracranialConsider second CT to assess progression of intracranial hemorrhage.hemorrhage.  A plan for access to emergent neurosurgical consultation isA plan for access to emergent neurosurgical consultation is highly recommended.highly recommended.
    44. 44. Acute Ischemic Stroke Protocol ER arrival Triage nurse confirm stroke onset time < 4.5 hours ER Resident performs Rapid evaluation (5 minutes) 1.exact time of onset 2.important history 3.quick neurological evaluation STAT CT and blood work Neurology Resident receives ER stroke page and proceeds to ER brief history & physical exam Page Stroke consultant Head CT findings, laboratory data, NIH stroke scale Confirm the criteria fulfilling thrombolytic therapy for ischemic stroke Family’s agreement for thrombolytic therapy Stroke onset < 4.5 hours IV-tPA treatment Patient is admitted to Stroke ICU for intensive monitoring/care Stroke onset 4.5-8 hours IA t therapy /device Call Neuroradiologists IA thrombolysis/device
    45. 45.  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 hrsCase 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 4.5 hrs.window period extended upto 4.5 hrs.
    46. 46. OUR STROKE TEAM  NeurologistNeurologist  NeurosurgeonNeurosurgeon  IntensivistIntensivist  NeuroradiologistNeuroradiologist  NeuropathologistNeuropathologist  NeurophysiotherepistNeurophysiotherepist  RMOS,Techs,Trained staffRMOS,Techs,Trained staff
    47. 47. TAKE HOME MESSAGE  IV r TPA IS RECOMMENDEDIV r TPA IS RECOMMENDED THEREPY FOR SELECTED PATIENTSTHEREPY FOR SELECTED PATIENTS WHO REACH HOSPITAL WITHIN 4.5WHO REACH HOSPITAL WITHIN 4.5 HOURS OF STROKE ONSET.HOURS 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.
    48. 48. TAKE HOME MESSAGETAKE HOME MESSAGE  At 3 months 30% more likely to have minimalAt 3 months 30% more likely to have minimal or no disability following thrombolysis.or no disability following thrombolysis.  There should be no protocol violation otherThere should be no protocol violation other wise more complications.wise more complications.  We have to increase awareness among patients,We have to increase awareness among patients, general public and doctors regarding beneficialgeneral public and doctors regarding beneficial effects of stroke thrombolysis.effects of stroke thrombolysis.
    49. 49. World Stroke day- 29 octoberWorld Stroke day- 29 october WSO Slogan- entitled ‘Because I care..WSO Slogan- entitled ‘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
    50. 50. THANK YOUTHANK YOU

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