basics of stroke(cva) management

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Basics of Stroke and Basics of Stroke and Alteplase (Actilyse) Alteplase (Actilyse) Dr(Lt Col) Ashutosh Ojha Dr(Lt Col) Ashutosh Ojha 151 Base Hospital 151 Base Hospital

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How to approach a case of Stroke in Hospital setting

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Page 1: Basics of stroke(CVA) Management

Basics of Stroke and Basics of Stroke and Alteplase (Actilyse)Alteplase (Actilyse)

Dr(Lt Col) Ashutosh OjhaDr(Lt Col) Ashutosh Ojha

151 Base Hospital151 Base Hospital

Page 2: Basics of stroke(CVA) Management

What Is Stroke ?What Is Stroke ?

A stroke occurs when blood flow to the brain is interrupted by

a blocked or burst blood vessel

When brain tissue is deprived of blood

flow, neurons die within minutes.

Surrounding a core of infarction is an

“ischemic penumbra,” poorly perfused but

viable tissue at risk for imminent

infarction.

The goal of acute stroke care is the revival and rescue of the

ischemic penumbra by rapid restoration of blood flow.

The goal of acute stroke care is the revival and rescue of the

ischemic penumbra by rapid restoration of blood flow.

Page 3: Basics of stroke(CVA) Management

What is specific to stroke in India?What is specific to stroke in India?

• Analysis of community surveys from different regions of

India shows a crude stroke prevalence rate of about 203 per

100,000 population above 20 years of age, amounting to a

total of about 1 million cases.

• Most studies carried out in India show that about 10% to 15% of

strokes occur in the population below 40 years, which is a higher

proportion compared with other countries

ACNR •2007

Page 4: Basics of stroke(CVA) Management

Time is brainTime is brain

• The phrase “time is brain” emphasizes

that human nervous tissue is rapidly and

irretrievably lost as stroke progresses and

that

- therapeutic interventions should be

emergently pursued.

• This general call to action in acute stroke

care was adapted from its predecessor in

acute coronary care (“time is muscle”), both

tracing their lineage to Benjamin Franklin’s

original aphorism, “time is money.”Stroke ,2006

Page 5: Basics of stroke(CVA) Management

Estimated Pace of Neural Circuitry Loss in Estimated Pace of Neural Circuitry Loss in Typical Large Vessel, Supratentorial Acute Typical Large Vessel, Supratentorial Acute Ischemic StrokeIschemic Stroke

Stroke ,2006

Every minute if stroke is untreated, the average patient loses 1.9

million neurons, 13.8 billion synapses, and 12 km (7 miles) of axonal

fibers.

Each hour in which treatment fails to occur, the brain loses as many

neuron as it does in almost 3.6 years of normal aging.

Page 6: Basics of stroke(CVA) Management

Blood Supply to BrainBlood Supply to Brain

The brain represents about 2% of The brain represents about 2% of total body weighttotal body weight

The brain accounts for 15-20% of The brain accounts for 15-20% of the body’s blood supplythe body’s blood supply

Brain cells have the highest Brain cells have the highest priority for bloodpriority for blood

Page 7: Basics of stroke(CVA) Management

Blood Supply to the Brain

The carotid and vertebrobasilar arteries form the Circle of

Willis

Other arteries arise from here and travel to all parts of the

brain:

• Anterior cerebral artery (ACA)

• Middle cerebral artery (MCA)

• Posterior cerebral artery (PCA)

Page 8: Basics of stroke(CVA) Management

Transient Ischemic Transient Ischemic AttackAttack TIA was traditionally defined as a TIA was traditionally defined as a

neurological deficit, the symptoms of which neurological deficit, the symptoms of which are defined CURED completely within 24 are defined CURED completely within 24 hourshours

The current definition of TIA isThe current definition of TIA is

Acute onset neurological dysfunction, due to Acute onset neurological dysfunction, due to focal brain ischemia, which completely focal brain ischemia, which completely resolves within 60 minutesresolves within 60 minutes

No evidence of cerebral ischemiaNo evidence of cerebral ischemia

Page 9: Basics of stroke(CVA) Management

Stroke - DefinitionStroke - Definition

A stroke is defined by the sudden onset of a A stroke is defined by the sudden onset of a neurologic deficit that is attributable to a neurologic deficit that is attributable to a focal vascular causefocal vascular cause

Therefore stroke can be explained as death Therefore stroke can be explained as death or dysfunction of brain tissue due to or dysfunction of brain tissue due to occlusion or hemorrhage of brain’s arteriesocclusion or hemorrhage of brain’s arteries

The pattern of resulting neurological damage The pattern of resulting neurological damage differs according to whether the supply to the differs according to whether the supply to the posterior or anterior artery has interruptedposterior or anterior artery has interrupted

Page 10: Basics of stroke(CVA) Management

There are two types of stroke:

Strokes can be classified into two main categories, including the

following:

•Ischemic strokes (Incidence - 85%) - strokes caused by blockage of an

artery.

•Hemorrhagic strokes (Incidence - 15%) - strokes caused by bleeding.

Ischemic stroke•An ischemic stroke occurs when a blood vessel that supplies the brain

becomes blocked or "clogged" and impairs blood flow to part of the brain.

•The brain cells and tissues begin to die within minutes from lack of

oxygen and nutrients.

•The area of tissue death is called an infarct.

Page 11: Basics of stroke(CVA) Management

•About 85 percent of strokes fall

into this category. Ischemic

strokes are further divided into

two groups, including the

following:

Thrombotic strokes -

caused by a blood clot that

develops in the blood vessels

inside the brain.

Embolic strokes - caused

by blood clot or plaque

debris that develops

elsewhere in the body and

then travels to one of the

blood vessels in the brain via

the bloodstream.

Ischemic stroke

Page 12: Basics of stroke(CVA) Management

Hemorrhagic stroke

•Hemorrhagic strokes occur when a

blood vessel that supplies the brain

ruptures and bleeds.

•Hemorrhagic strokes are divided into

two main categories, including the

following:

Intra-cerebral hemorrhage -

bleeding from the blood vessels

within the brain.

Subarachnoid hemorrhage -

bleeding in the subarachnoid space

(the space between the brain and

the membranes that cover the

brain).

Page 13: Basics of stroke(CVA) Management

PathophysiologicalPathophysiological ClassificationClassification

Page 14: Basics of stroke(CVA) Management

What Are the Effects of Stroke?What Are the Effects of Stroke?

Page 15: Basics of stroke(CVA) Management

Symptoms of StrokeSymptoms of Stroke

Ischemic StrokeIschemic Stroke

Sudden numbness or Sudden numbness or weakness of face, arm or legweakness of face, arm or leg

Sudden confusion, difficulty in Sudden confusion, difficulty in speech and understandingspeech and understanding

Sudden difficulty in vision in Sudden difficulty in vision in one or both eyes, include loss one or both eyes, include loss of vision & double visionof vision & double vision

Sudden difficulty in walking, Sudden difficulty in walking, dizziness, loss of balance and dizziness, loss of balance and coordination including limb coordination including limb ataxiaataxia

Hemorrhagic StrokeHemorrhagic Stroke

Sudden severe headacheSudden severe headache

Sudden decline in level of Sudden decline in level of conciousness (may include conciousness (may include fainting, confusion, fainting, confusion, convulsions or coma)convulsions or coma)

Rapid onset of nausea and Rapid onset of nausea and vomittingvomitting

Page 16: Basics of stroke(CVA) Management

Signs of StrokeSigns of Stroke

Abrupt onset of cognitive, motor and/or Abrupt onset of cognitive, motor and/or sensory deficitssensory deficits

Dysphasia and dysarthriaDysphasia and dysarthria

Disturbance in coordinationDisturbance in coordination

Facial droopFacial droop

Loss of conciousnessLoss of conciousness

Page 17: Basics of stroke(CVA) Management

What are the risks factors for What are the risks factors for Ischemic Stroke?Ischemic Stroke?

Modifiable RisksModifiable Risks– HTNHTN– CAD/Carotid Disease/PVDCAD/Carotid Disease/PVD– Atrial FibrillationAtrial Fibrillation– DiabetesDiabetes– WeightWeight– High Cholesterol/DietHigh Cholesterol/Diet– Lack of exerciseLack of exercise– ETOH/Drug abuseETOH/Drug abuse– Coagulopathy- Cancer, Coagulopathy- Cancer,

Sickle Cell AnemiaSickle Cell Anemia– PFO- Patent Foramen OvalePFO- Patent Foramen Ovale

Non-Modifiable RisksNon-Modifiable Risks– Age->55Age->55– Race- African Americans Race- African Americans

have 2x the risk of death have 2x the risk of death and disability. Asians have and disability. Asians have 1.4x the risk of death and 1.4x the risk of death and disability.disability.

– Sex- 9% greater chance in Sex- 9% greater chance in men. (61% of stroke deaths men. (61% of stroke deaths occur in women)occur in women)

– Previous Stroke or TIAPrevious Stroke or TIA– Family History of StrokeFamily History of Stroke

Page 18: Basics of stroke(CVA) Management

STROKE TREATMENT

Page 19: Basics of stroke(CVA) Management

ACT F.A.S.T.ACT F.A.S.T.

FFACE    ACE    ASK THE PERSON TO SMILE.ASK THE PERSON TO SMILE.

DOES ONE SIDE OF THE FACE DROOP? DOES ONE SIDE OF THE FACE DROOP?

AARMS    RMS    ASK THE PERSON TO RAISE BOTH ARMS.ASK THE PERSON TO RAISE BOTH ARMS.

DOES ONE ARM DRIFT DOWNWARD? DOES ONE ARM DRIFT DOWNWARD?

SSPEECHPEECH   

ASK THE PERSON TO REPEAT A SIMPLE ASK THE PERSON TO REPEAT A SIMPLE SENTENCE.SENTENCE.

ARE THE WORDS SLURRED?  CAN HE/SHE ARE THE WORDS SLURRED?  CAN HE/SHE REPEAT THE SENTENCE CORRECTLY?REPEAT THE SENTENCE CORRECTLY?

TTIME    IME   

IF THE PERSON SHOWS ANY OF THESE IF THE PERSON SHOWS ANY OF THESE SYMPTOMS, TIME IS IMPORTANT. SYMPTOMS, TIME IS IMPORTANT. 

CALL FOR EMERGENCY OR GET TO THE CALL FOR EMERGENCY OR GET TO THE HOSPITAL FAST. BRAIN CELLS ARE DYING. HOSPITAL FAST. BRAIN CELLS ARE DYING.

Page 20: Basics of stroke(CVA) Management

Immediate Diagnostic Studies: Evaluation of Immediate Diagnostic Studies: Evaluation of aaPatient With Suspected Acute Ischemic Patient With Suspected Acute Ischemic StrokeStroke

Stroke 2007;38;1655-1711;

Page 21: Basics of stroke(CVA) Management

Management of strokeManagement of stroke

• Management of stroke, ischemic stroke in particular, has

undergone a sea change since the landmark

- National Institute of Neurological Disorders and Stroke

(NINDS) Recombinant Tissue Plasminogen Activator (rt-PA) stroke

Study earned US-FDA approval in 1996.

• The window of opportunity for salvaging the ischemic tissue at risk

is first 3 h since onset of stroke.

• Trials/Guidelines now support the window till 4.5 hrs in treatment

of stroke MJAFI, Vol. 65, No. 1, 2009

Page 22: Basics of stroke(CVA) Management

Critical Time windowCritical Time window

• From the moment the patient arrives at the door, every minute

counts, and the only justifiable delays would be for performing

brain imaging studies to exclude hemorrhage and for obtaining the

results of a few simple laboratory tests.

Every minute matters during a strokeEvery minute matters during a stroke

Page 23: Basics of stroke(CVA) Management

Alteplase only thrombolytic Alteplase only thrombolytic approved for treatment of approved for treatment of Acute ischemic strokeAcute ischemic stroke

Page 24: Basics of stroke(CVA) Management

Mode of ActionMode of Action

•The active ingredient of ACTILYSE is alteplase, a recombinant human tissue-type

plasminogen activator, a glycoprotein, which activates plasminogen directly to

plasmin

•When administered intravenously, alteplase remains relatively inactive in the

circulatory system

•Once bound to fibrin, it is activated, inducing the conversion of plasminogen to

plasmin leading to the dissolution of the fibrin clot

Page 25: Basics of stroke(CVA) Management

Pharmacokinetics

•ACTILYSE is cleared rapidly from the circulating blood and metabolised mainly by

the liver (plasma clearance 550 - 680 ml/min.)

• The relevant plasma half-life T1/2 alpha is 4 - 5 minutes

•This means that after 20 minutes less than 10% of the initial value is present in the

plasma. For the residual amount remaining in a deep compartment, a beta-half-life

of about 40 minutes was measured.

Page 26: Basics of stroke(CVA) Management

StorageStorage

Protect the lyophilised substance from lightProtect the lyophilised substance from light

The reconstituted solution can be kept for 8 The reconstituted solution can be kept for 8 & 24 hours in room temperature and & 24 hours in room temperature and refrigerator respectivelyrefrigerator respectively

During reconstitution the solution needs to During reconstitution the solution needs to be mixed with gentle swirl, not to be be mixed with gentle swirl, not to be shakenshaken

Page 27: Basics of stroke(CVA) Management

IndicationIndication

1. Thrombolytic treatment in acute myocardial infarction.90 minutes (accelerated) dose regimen for patients in whom treatment can be started within 6 h of symptom onset;3 hour dose regimen for patients in whom treatment can be started between 6 12 h after symptom onset.

2.Thrombolytic treatment in acute massive pulmonary embolism with hemodynamic instability

The diagnosis should be confirmed whenever possible by objective means such as pulmonary angiography or non-invasive procedures such as lung scanning

3.Thrombolytic treatment of acute ischaemic strokeTreatment should only be initiated within 3 hours after the onset of

stroke symptoms and after exclusion of intracranial haemorrhage by appropriate imaging techniques such as cranial computerised tomography (CT).

Page 28: Basics of stroke(CVA) Management

Ischemic Stroke Ischemic Stroke

The recommended dose is 0.9 mg/kg (maximum of 90 mg) infused over 60 minutes

with 10% of the total dose administered as an initial intravenous bolus. Therapy

should be initiated as early as possible within 3 hours after onset of symptoms.

Adjunctive therapy:

The safety and efficacy of this regimen with concomitant administration of heparin

and acetylsalicylic acid during the first 24 hours after the symptom-onset has not

been investigated sufficiently.

Therefore, administration of acetylsalicylic acid or

intravenous heparin should be avoided in the first 24

hours after treatment with ACTILYSE

Page 29: Basics of stroke(CVA) Management

Pulmonary embolismPulmonary embolism

A total dose of 100 mg should be administered in 2 hours. The most experience available

is with the following dose regimen:

10 mg as an intravenous bolus over 1 - 2 minutes, 90 mg as an intravenous infusion over

two hours.

The total dose should not exceed 1.5 mg/kg in patients with a body weight below 65 kg.

Adjunctive therapy:

After treatment with ACTILYSE heparin therapy should be initiated (or resumed) when

aPTT values are less than twice the upper limit of normal. The infusion should be adjusted

to maintain aPTT between 50 - 70 seconds (1.5 to 2.5 fold of the reference value).

Page 30: Basics of stroke(CVA) Management

In the indication acute ischemic stroke the following contraindications apply in addition:

•symptoms of ischemic attack began more than 4.5 hours prior to infusion start or when time of symptom onset is unknown•symptoms of acute ischemic stroke that were either rapidly improving or only minor before start of infusion•severe stroke as assessed clinically (e.g. NIHSS>25) and/or by appropriate imaging techniques•seizure at the onset of stroke•history of previous stroke or serious head-trauma within three months •a combination of previous stroke and diabetes mellitus•administration of heparin within 48 hours preceding the onset of stroke with an elevated activated partial thromboplastin time (aPTT) at presentation•platelet count of less than 100,000 / mm3

•systolic blood pressure > 185 or diastolic blood pressure > 110 mmHg, or aggressive management (IV medication) necessary to reduce blood pressure to these limits•blood glucose < 50 or > 400 mg/dl

ACTILYSE is not indicated for the therapy of acute stroke in children and adolescents under 18 years or adults over 80 years of age.

Contraindications

Page 31: Basics of stroke(CVA) Management

InteractionsNo formal interaction studies with ACTILYSE and medicinal products commonly administered in

patients with acute myocardial infarction have been performed.

Medicinal products that affect coagulation or those that alter platelet function may increase the

risk of bleeding prior to, during or after ACTILYSE therapy.

Concomitant treatment with ACE inhibitors may enhance the risk of suffering an anaphylactoid

reaction, as in the cases describing such reactions a relatively larger proportion of patients were

receiving ACE inhibitors concomitantly.

Pregnancy and lactationThere is very limited experience with the use of ACTILYSE during pregnancy and lactation. In

cases of an acute life-threatening disease the benefit has to be evaluated against the potential

risk.

It is not known if alteplase is excreted into breast milk.

Page 32: Basics of stroke(CVA) Management

Thumb Rules of Thumb Rules of ThrombolysisThrombolysis

AISAIS Onset of symptoms within 4.5 Onset of symptoms within 4.5

hourshours Age – 18 to 80 yearsAge – 18 to 80 years NIHSS – 4-25NIHSS – 4-25 BP - <185/110 mm of HgBP - <185/110 mm of Hg Blood glucose - <50-400 ml/dlBlood glucose - <50-400 ml/dl

Page 33: Basics of stroke(CVA) Management

Treatment of AIS – follow-up Treatment of AIS – follow-up during & post thrombolysisduring & post thrombolysis

Neurological assessments – every 15 minutes during the Neurological assessments – every 15 minutes during the infusion, every 30 minutes thereafter for 6 hours, then infusion, every 30 minutes thereafter for 6 hours, then hourly until 24 hourshourly until 24 hours

Measure BP – every 15 minutes for the first 2 hours, Measure BP – every 15 minutes for the first 2 hours, every 30 minutes for the next 6 hours, then hourly until every 30 minutes for the next 6 hours, then hourly until 24 hours. BP has to be kept within 180/105 mm of Hg24 hours. BP has to be kept within 180/105 mm of Hg

Delay placement of nasogastric tubes, catheters etcDelay placement of nasogastric tubes, catheters etc

A follow-up CT at 24 hours before starting anticoagulantsA follow-up CT at 24 hours before starting anticoagulants

An emergency if patient develops severe headache, An emergency if patient develops severe headache, acute HT, nausea or/and vomitingacute HT, nausea or/and vomiting

Page 34: Basics of stroke(CVA) Management

Complications of IV Complications of IV Thrombolysis with AlteplaseThrombolysis with Alteplase

Include intracranial and extracranial hemorrhagesInclude intracranial and extracranial hemorrhages

Most common and dreaded complication ICHMost common and dreaded complication ICH

ICHs are divided into symptomatic and asymptomatic ICHs are divided into symptomatic and asymptomatic ICHsICHs

Symptomatic ICHs are mostly large hemorrhages, Symptomatic ICHs are mostly large hemorrhages, found as parenchymal hematomas in CTfound as parenchymal hematomas in CT

Asymptomatic ICHs occur commonly during the Asymptomatic ICHs occur commonly during the natural course of cerebral infarct and don’t have natural course of cerebral infarct and don’t have significant negative impact on the final outcomesignificant negative impact on the final outcome

Page 35: Basics of stroke(CVA) Management

Bleeding and its Bleeding and its ManagementManagement

It is not necessary to replace the coagulation factors due to It is not necessary to replace the coagulation factors due to the short half life and moderate effect of Alteplase on the short half life and moderate effect of Alteplase on systemic coagulation factorssystemic coagulation factors

Most bleeds can be managed by interruption of thrombolytic Most bleeds can be managed by interruption of thrombolytic & anticoagulant therapy, volume replacement or manual & anticoagulant therapy, volume replacement or manual pressure applied to an incompetent vesselpressure applied to an incompetent vessel

Patients who don’t respond transfusion products may be Patients who don’t respond transfusion products may be used judiciouslyused judiciously

Transfusion of fresh frozen plasma, cryoprecipitates, Transfusion of fresh frozen plasma, cryoprecipitates, platelets should be considered with clinical and laboratory platelets should be considered with clinical and laboratory reassessment after each administrationreassessment after each administration

Antifibrinolytic agents are available as last alternativeAntifibrinolytic agents are available as last alternative

Page 36: Basics of stroke(CVA) Management

Characteristics of Patients With Ischemic Characteristics of Patients With Ischemic Stroke Who Could Be Treated With rt-PAStroke Who Could Be Treated With rt-PA

Diagnosis of ischemic stroke causing measurable neurological deficitDiagnosis of ischemic stroke causing measurable neurological deficit

The neurological signs should not be clearing spontaneously.The neurological signs should not be clearing spontaneously.

The neurological signs should not be minor and isolated.The neurological signs should not be minor and isolated.

Caution should be exercised in treating a patient with major deficits.Caution should be exercised in treating a patient with major deficits.

The symptoms of stroke should not be suggestive of subarachnoid The symptoms of stroke should not be suggestive of subarachnoid

hemorrhage.hemorrhage.

Onset of symptoms <3 hours before beginning treatment ( has been Onset of symptoms <3 hours before beginning treatment ( has been

increase to 4.5hr as per 2008 ESO guidelines , 2010 ISA guidelines increase to 4.5hr as per 2008 ESO guidelines , 2010 ISA guidelines

and also by ASA in specific condition)and also by ASA in specific condition)

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

Stroke 2009, Stroke 2007

Page 37: Basics of stroke(CVA) Management

Characteristics of Patients With Characteristics of Patients With Ischemic Stroke Who Could Be Ischemic Stroke Who Could Be Treated With rt-PATreated With rt-PA

No myocardial infarction in the previous 3 monthsNo myocardial infarction in the previous 3 months

No gastrointestinal or urinary tract hemorrhage in previous 21 daysNo gastrointestinal or urinary tract hemorrhage in previous 21 days

No major surgery in the previous 14 daysNo major surgery in the previous 14 days

No arterial puncture at a noncompressible site in the previous 7 No arterial puncture at a noncompressible site in the previous 7

daysdays

No history of previous intracranial hemorrhageNo history of previous intracranial hemorrhage

Blood pressure not elevated (systolic <185 mm Hg and diastolic Blood pressure not elevated (systolic <185 mm Hg and diastolic

<110 mm Hg)<110 mm Hg)

No evidence of active bleeding or acute trauma (fracture) on No evidence of active bleeding or acute trauma (fracture) on

examinationexamination

Not taking an oral anticoagulant or, if anticoagulant being taken, Not taking an oral anticoagulant or, if anticoagulant being taken,

INR≤ 1.7INR≤ 1.7

Stroke 2007;38;1655-1711;

Page 38: Basics of stroke(CVA) Management

Characteristics of Patients With Ischemic Characteristics of Patients With Ischemic Stroke Who Could Be Treated With rt-PAStroke Who Could Be Treated With rt-PA

If receiving heparin in previous 48 hours, aPTT must be in If receiving heparin in previous 48 hours, aPTT must be in

normal range.normal range.

Platelet count ≥100 000 mm3Platelet count ≥100 000 mm3

Blood glucose concentration ≥ 50 mg/dL (2.7 mmol/L)Blood glucose concentration ≥ 50 mg/dL (2.7 mmol/L)

No seizure with postictal residual neurological No seizure with postictal residual neurological

impairmentsimpairments

CT does not show a multilobar infarction (hypodensity CT does not show a multilobar infarction (hypodensity

>1/3 cerebral hemisphere).>1/3 cerebral hemisphere). Stroke 2007;38;1655-1711;

Page 39: Basics of stroke(CVA) Management

Key pointsKey points

Young stroke patientsYoung stroke patients Time is at premiumTime is at premium Early identification Early identification Early institution of RxEarly institution of Rx Good and very satisfying resultGood and very satisfying result Drug available ,Neuro-imaging Drug available ,Neuro-imaging

available available Previous cases encouraging resultPrevious cases encouraging result

Page 40: Basics of stroke(CVA) Management

Thank You….!!!!Thank You….!!!!