Thrombolytic Therapy of Thrombolytic Therapy of Acute Ischemic strokeAcute Ischemic stroke

Dr Parth Sarthi DebDr Parth Sarthi Deb

Dr Srikant JawalkarDr Srikant Jawalkar

Apollo Hospital HyderabadApollo Hospital Hyderabad

BackgroundBackground

Neuro-protection and anti-thrombotic Neuro-protection and anti-thrombotic

treatment have not changed the treatment have not changed the

outcome of stroke outcome of stroke

Only effective way to protect ischemic Only effective way to protect ischemic

neurons is re-vascularization in timeneurons is re-vascularization in time

FactsFacts

The ischemia threshold for The ischemia threshold for neuronal death will never changeneuronal death will never change

Mode of re-vascularization can be Mode of re-vascularization can be Mechanical or PharmacologicalMechanical or Pharmacological

Most effective and practical way to Most effective and practical way to achieve this is still awaitedachieve this is still awaited

What shall we do ?What shall we do ?

1. 1. WaitWait till the result of double blind till the result of double blind placebo controlled multicentric trial of placebo controlled multicentric trial of ideal re-vascularization is outideal re-vascularization is out

2. 2. Satisfied Satisfied with neuro-protection and with neuro-protection and anti-thrombotic measuresanti-thrombotic measures

3. 3. TryTry thrombolysis with caution when thrombolysis with caution when ever suitableever suitable

PatientsPatients

Period: Period: 1992-1992-0000 Total ischemic strokesTotal ischemic strokes 801801 Thrombolysis done Thrombolysis done 3636 Male Male 2929 FemalesFemales 77 Age in yearsAge in years 20-8020-80

Inclusion CriteriaInclusion Criteria

A.A. Clinical evidence for an Clinical evidence for an ischemic strokeischemic stroke

B. Normal CT ScanB. Normal CT Scan

C.C. Age >18 yearsAge >18 years

D.D. Onset of stroke Ant cir Onset of stroke Ant cir 6 hr6 hr

Post cir Post cir 12 hr12 hr

E.E. Normal BT, CT, PT, PTT and Normal BT, CT, PT, PTT and platelet platelet

Exclusion CriteriaExclusion Criteria

A. A. Stroke or serious head trauma in past 3 Stroke or serious head trauma in past 3 monthsmonths

B.B. Major surgery or invasive procedure Major surgery or invasive procedure within past 14 dayswithin past 14 days

C.C. GI or urinary bleeding within past GI or urinary bleeding within past 21 days21 days

D.D. Puncture of noncompressible artery Puncture of noncompressible artery or biopsy of internal organ within past 7 or biopsy of internal organ within past 7 daysdays

E.E. Ongoing alcohol or drug abuseOngoing alcohol or drug abuse

Exclusion Criteria cont..Exclusion Criteria cont..

F.F. Seizure preceding or during strokeSeizure preceding or during stroke

G.G. History of intracranial hemorrhage History of intracranial hemorrhage (including subarachnoid bleeds) or (including subarachnoid bleeds) or known history of cerebral vascular known history of cerebral vascular malformations (including aneurysms or malformations (including aneurysms or arteriovenous malformations)arteriovenous malformations)

H.H. Pericarditis, endocarditis, septic Pericarditis, endocarditis, septic emboli, recent pregnancy, or active emboli, recent pregnancy, or active inflammatory bowel diseaseinflammatory bowel disease

Thrombolysis in acute Thrombolysis in acute strokestroke

Within 3 hour of Stroke Small Vessel

Medium Vessel

IV rTPA/URK

Large Vessel

IA rTPA/URK

Stop

Thrombolytic AgentsThrombolytic Agents

Streptokinase: Streptokinase: IA IA 1-1.5 lakh units1-1.5 lakh units

IV IV 2.5-10 lakh units2.5-10 lakh units

Urokinase:Urokinase: IV IV 5-10 lakh units5-10 lakh units

IA 5-10 lakh unitsIA 5-10 lakh units

rTPA:rTPA: IAIA 10-40 mg10-40 mg

IVIV 40-50 mg40-50 mg

Route of AdministrationRoute of Administration

DrugDrug IVIV IAIA TotalTotal

STKSTK 77 22 99

URKURK 1515 66 2121

rTPArTPA 44 22 66

TotalTotal 2626 1010 3636

End Point of TreatmentEnd Point of Treatment

Total calculated dose givenTotal calculated dose given

Patient showed significant improvementPatient showed significant improvement

Significant bleeding complicationSignificant bleeding complication

Severe allergic reactionSevere allergic reaction

AgeAge MaleMale FemaleFemale TotalTotal

20-3920-39 55 -- 55

40-5940-59 1212 55 1717

60-8060-80 1212 22 1414

TotalTotal 2929 77 3636

Age Sex DistributionAge Sex Distribution

Arterial Territory and SeverityArterial Territory and Severity

ArteryArtery ConsciousConscious UnconsciouUnconsciouss

TotalTotal

ACAACA 1616 1111 2727

PCAPCA 22 77 99

TotalTotal 1818 1818 3636

Outcome and Agent usedOutcome and Agent used

RecoveryRecovery STKSTK URKURK rTPArTPA TotalTotal

IndependenIndependentt

44 1313 22 1919

DependentDependent 22 44 11 77

DeathDeath 33 44 33 1010

TotalTotal 99 2121 66 3636

Outcome and Arterial TerritoryOutcome and Arterial Territory

RecoverRecoveryy

ACAACA PCAPCA TotalTotal

ConCon UncUnc ConCon UncUnc

IndInd 1212 11 22 44 1919

DepDep 33 33 -- 11 77

DeathDeath 11 77 -- 22 1010

TotalTotal 1616 1111 22 77 3636

Outcome and Timing of TreatmentOutcome and Timing of Treatment

OutcomOutcomee

<1<1hh

1-3h1-3h 3-6h3-6h TotalTotal

IndInd 66 44 99 1919

DepDep -- 11 66 77

DeathDeath 33 11 66 1010

TotalTotal 99 66 2121 3636

Outcome and CT scanOutcome and CT scan

OutcomeOutcome NormaNormall

EarlyEarly TotalTotal

IndependentIndependent 1515 11 1616

DependentDependent 55 22 77

DeathDeath 77 33 1010

TotalTotal 2626 66 3333

Complication of therapyComplication of therapy

ComplicationComplication STKSTK URKURK rTPArTPA TotalTotal

Skin RashSkin Rash -- 11 -- 11

BronchospasmBronchospasm -- 11 11 22

AnaphylaxisAnaphylaxis -- 11 22 33

Gum bleedGum bleed -- 11 11 22

Gastric bleedGastric bleed 22 11 -- 33

Urinary bleedUrinary bleed -- 11 -- 11

IC bleedIC bleed -- 11 -- 11

Hem transHem trans 11 -- -- 11

Toxic edemaToxic edema 22 55 22 88

IC spasmIC spasm -- 11 -- 11

ConclusionConclusion

Outcome was not related to the Drug usedOutcome was not related to the Drug used Ant circulation minor stroke and posterior Ant circulation minor stroke and posterior

circulation stroke has better prognosiscirculation stroke has better prognosis Ant. circulation major stroke did well on IA Ant. circulation major stroke did well on IA

thrombolysis.thrombolysis. Normal CT before treatment was not Normal CT before treatment was not

related to good outcome. But abnormal CT related to good outcome. But abnormal CT has poor outcome.has poor outcome.

Hemorrhagic complication are dose related.Hemorrhagic complication are dose related.

Thank YouThank You