DR VINEET SURI

MANAGEMENT OF ISCHAEMIC STROKEMANAGEMENT OF ISCHAEMIC STROKE

DR. VINIT SURIMD (Medicine), DM (Neurology)

Sr. Consultant NeurologistIndraprastha Apollo Hospital

STROKE IS A MEDICAL EMERGENCY

“ “ BRAIN ATTACK” BRAIN ATTACK”

‘ACUTE NEUROVASCULAR SYNDROME’‘ACUTE NEUROVASCULAR SYNDROME’

FAST

•Face•Arm•Speech•Test

ACT FAST TIME IS BRAINTIME IS BRAIN

EVIDENCE OF EFFICACY

0.50.5TreatmentTreatment

betterbetter

Stroke unit treatmentStroke unit treatment

0 – 3 hr IV TPA0 – 3 hr IV TPA

0 – 6 hr IA Prourokinase0 – 6 hr IA Prourokinase

HemicraniectomyHemicraniectomy

1.01.0 22PlaceboPlacebobetterbetter

Acute aspirinAcute aspirin

OddsOddsRatioRatio

0.940.94

0.780.78

0.660.66

0.580.58

0.330.33

No. of deadNo. of deadOr dependentOr dependent

Avoided / 1000 pts.Avoided / 1000 pts.

1313

5050

140140

500500

PRE-HOSPITAL CARE

• Stroke is a medical emergency and all patients should be hospitalized urgently. [even if minor stroke – 25-40% deteriorate over 24-48 hrs] .Avoid wait & watch

• FAST

• Blood sugar estimation and correction of hypoglycemia (<60 mg%) – Exclude Stroke mimics

• Aspirin to be administered preferably after CT Scan [Aspirin in 1st 48 hrs] unless significant delay. No harm documented in hemorrhagic stroke.

• Do not lower BP unless Sys > 220 Dias > 120. Do not use sublingual nifedipine

TRIAGE MANAGEMENT

• Stabilization of ABC

• IV access – NS @ 50 ml/hr in nonparalysed arm

• Continuous cardiac monitoring

• Oxygen saturation monitoring for 48-72 hrs

1. Stabilization

2. Establish diagnosis (exclude stroke mimics)

3. Stroke Scale (NIHSS score)

4. Imaging – CT /MRI

5. Investigations

6. Thrombolysis – IV / IA

7. Shift to Stroke ICU

TRIAGE MANAGEMENT

1. Stabilization




5. Investigations



STROKE MIMICSSTROKE MIMICS-- Post ictal deficietPost ictal deficiet-- Neurogenic migraineNeurogenic migraine-- Subdural hematomaSubdural hematoma-- Brain abscessBrain abscess-- TumorTumor-- Hypertensive encephalopathyHypertensive encephalopathy-- Multiple SclerosisMultiple Sclerosis-- Spinal cord or disc diseaseSpinal cord or disc disease-- Bells palsyBells palsy-- CerebritisCerebritis

CT helpful but CT helpful but MRI is significantly MRI is significantly better, especially better, especially with DWI establishing infarct beyond 39 minuteswith DWI establishing infarct beyond 39 minutes

Absence of DWI restricted pathology – look for an Absence of DWI restricted pathology – look for an alternate causealternate cause

TRIAGE MANAGEMENT

1. Stabilization




5. Investigations



NIHSS scoreNIHSS score

• NIHSS < 10 – 60 – 70% favourable outcome NIHSS < 10 – 60 – 70% favourable outcome at 1 yr.at 1 yr.

• NIHSS > 20 4 – 16% favourable outcome at 1 NIHSS > 20 4 – 16% favourable outcome at 1 yr.yr.

• NIHSSNIHSS < 10 – IVTPA< 10 – IVTPA> 25 – IVTPA contra indicated > 25 – IVTPA contra indicated

NIHSS SCORE1A Level of 0 – Alert

conciousness 1 – Drowsy2 – Obtunded3 – Coma

1B Orientation 0 – Answers both correctly questions (2) 1 – Answers 1 correctly

2 – Answers neither correctly1C Response to 0 – Performs both correctly

commands (2) 1 – Performs 1 correctly2 – Performs neither

2 Gaze 0 – Normal horizontal movements1 – Partial gaze palsy2 – Complete gaze palsy

3 Visual fields 0 – No visual field defect1 – Partial hemianopsia2 – Complete hemianopsia3 – Bilateral hemianopsia

4 Facial 0 – Normalmovements 1 – Minor facial weakness

2 – Partial facial weakness3 – Complete unilateral palsy

5 Motor function 0 – No drift(ARM)a : Left 1 – Drift before 5 secsb : Right 2 – Falls before 10 secs

3 – No effort against gravity4 – No movement

66 Motor function Motor function 0 – No drift0 – No drift (Leg) (Leg) a : Lefta : Left 1 – Drift before 5 secs1 – Drift before 5 secsb : Rightb : Right 2 – Falls before 5 secs2 – Falls before 5 secs

3 – No effort against gravity3 – No effort against gravity4 – No movement4 – No movement

77 Limb AtaxiaLimb Ataxia 0 – No ataxia0 – No ataxia1 – Ataxia in one limb1 – Ataxia in one limb2 – Ataxia in two limbs2 – Ataxia in two limbs

88 SensorySensory 0 – No sensory loss0 – No sensory loss1 – Mild sensory loss1 – Mild sensory loss2 – Severe sensory loss2 – Severe sensory loss

99 LanguageLanguage 0 – Normal0 – Normal1 – Mild Aphasia1 – Mild Aphasia2 – Severe aphasia2 – Severe aphasia3 – Mute or global aphasia3 – Mute or global aphasia

1010 ArticulationArticulation 0 – Normal0 – Normal1 – Mild dysarthria1 – Mild dysarthria2 – Severe dysarthria2 – Severe dysarthria

1111 Extinction orExtinction or 0 – Absent0 – AbsentInattentionInattention 1 – Mild (loss 1 sensory 1 – Mild (loss 1 sensory modality)modality)

2 – Severe (loss 2 modalities)2 – Severe (loss 2 modalities)

TRIAGE MANAGEMENT

1. Stabilization




5. Investigations



NCCT HeadNCCT Head

I.I. CT sufficient to exclude CT sufficient to exclude hemorrhage and stroke mimics hemorrhage and stroke mimics and hence proceed with and hence proceed with thrombolysisthrombolysis

ii.ii. Short duration imagingShort duration imaging

iii.iii. Can be used despite Can be used despite pacemakers, valve pacemakers, valve replacement, restless patientsreplacement, restless patients

MRIADVANTAGES :i) Can detect ischemic areas within 39

minutes of onsetii) Can differentiate old from acute

infarctiii) Can detect posterior circulation and

lacunar strokeiv) Can give information about ischemic

penumbra (DWI + perfusion mismatch)

v) Can reveal intracranial vessel disease on MRA

vi) Can detect microbleeds

DISADVANTAGES :i) Time consumingii) Contra-indications (Pacemaker, Post

CABG, Valve replacement)

• CBC, PT, aPTT, LFT, KFT• ECG, Chest X-ray• Echo, Carotid Doppler

• Thrombolysis pts – Platelet count, RBS, PT if on anticoagulants or suspected coagulopathy

• Pulse oximetry• Cardiac monitoring (AF, arrhythmia)

Special tests :• TCD• Thrombotic profile• Collagen profile• ABG

TRIAGE MANAGEMENTTRIAGE MANAGEMENT

1.1. StabilizationStabilization

2.2. Establish diagnosis Establish diagnosis (exclude stroke mimics)(exclude stroke mimics)

3.3. Stroke Scale (NIHSS Stroke Scale (NIHSS score)score)

4.4. Imaging – CT /MRIImaging – CT /MRI

5.5. InvestigationsInvestigations

6.6. Thrombolysis – IV / IAThrombolysis – IV / IA

7.7. Shift to Stroke ICUShift to Stroke ICU

Stratify patients

•Recanalization therapy

•Stroke ICU General care

RECANALIZATION

• Intravenous• Intra arterial• Combined IV + IA• mechanical

THROMBOLYSIS IN STROKE

IV TPA :INCLUSION CRITERIA

Ischaemic strokeIschaemic stroke

Persistent neurological deficit beyond isolated sensory deficit or Persistent neurological deficit beyond isolated sensory deficit or ataxiaataxia

CT negative for hemorrhageCT negative for hemorrhage

Initiation of treatmentInitiation of treatment WITHIN THREE HOURSWITHIN THREE HOURS (( 4.5 hrs4.5 hrs))

THROMBOLYSIS IN STROKEIV TPA :EXCLUSION CRITERIA• > 4.5 hours since onset , Time uncertain• Oral anticoagulant use or PT > 15sec ( INR > 1.7)• Heparin use in 48 hours with prolonged PTT• Platelet count < 1.0 x 105 • Pretreatment BP > 180 systolic, > 110 diastolic• Prior stroke or head injury in 3 months• Acute MI in last 3 months• Major surgery in 2 weeks• Seizure at onset• GI or UT hemorrhage within 2 weeks• Arterial puncture at a noncompressible site within 7 days• Age > 80 years (?)• Known AVM / aneurysm


IV TPA - GUIDELINES

DOSAGE : DOSAGE : 0.9 mg / kg (50 mg vial / 20 mg vial) max 90 mg0.9 mg / kg (50 mg vial / 20 mg vial) max 90 mg

: 10 % bolus IV over 1 min,followed by 90 % infusion : 10 % bolus IV over 1 min,followed by 90 % infusion over 1 hr over 1 hr

Children : safety unclear : 0.5 mg / kgChildren : safety unclear : 0.5 mg / kg

Stop transfusion and stat CT Scan Brain if patient becomes Stop transfusion and stat CT Scan Brain if patient becomes drowsy, vomits, has severe headache or acute hypertensiondrowsy, vomits, has severe headache or acute hypertension


IV TPA - POST THROMBOLYSIS CARE :

– BP q 15 min x 6 hrs. Treat if systolic > 180, diastolic > 105

– Avoid central line, arterial line puncture for 24 hrs

– Avoid Ryle’s tube insertion for 24 hrs

– Avoid urinary catheterization during and for ½ hrs post TPA

– Mannitol to reduce oedema

– No antiplatelets, anticoagulants for 24 hrs

– CT after 24 hrs (earlier if neurological deterioration)

INTRA – ARTERIAL THROMBOLYSIS

INTRA-ARTERIAL THROMBOLYSIS

EVIDENCE : PROACT I STROKE 1998

6 hrs, 6 mg prouk - 67.7 % vs. 14.3% recanalization

(+ heparin) - 10 - 12 % excellent outcome at 3 months- 15.4 % vs. 7% hemorrhage

PROACT II JAMA 1999

6 hrs, 9 mg prouk - 40 % vs. 25% Rankin < 2 at 3 months

(heparin / no heparin) - 66% vs. 15%recanalization - hemorrhage 10%

J MUSIC (Japan’s multicentre stroke investigators collaboration)Inoue Cerebrovascular disease 2005 ; 19 : 225 – 228

Favourable outcome (m Ranking) 51% IATPA vs 34% control

Macleod Cerbrovasc Dis 2005 ; 20 : 12 – 17

15 pts, post circulation stroke within 24 hours, IA prouk vs conservative

Good outcome 4/7 IATPA vs 1/8 control


ADVANTAGES OF INTRA-ARTERIAL THROMBOLYSIS

• Better recanalization compared to IV TPA– IVTPA – 39% FDA approved– IATPA – 66%– MERCI device – 69% FDA approved

• Better in severe deficit (NIHSS > 20)

• Presentation between 3 – 6 hours in anterior circulation and 24 hours in posterior circulation

• Recent history of surgical procedure

• Occlusion of major cervical and or intracranial vessel


RECOMMENDATION (AHA / ASA / Adams et al Stroke 2007)

IA thrombolysis is an option for treatment of selected pts who have major stroke < 6 hrs duration due to occlusion of MCA and who are not otherwise candidates for IV TPA (Class I Level B)

• IA thrombolysis is reasonable in pts with contra-indications for IV TPA eg. Recent surgery (Class IIa Level C)

• Availability of intra-arterial thrombolysis should not preclude IV TPA (Class III Level C)

COMBINATION THERAPY (IV + IA TPA)

COMBINATION THERAPY

• Initiation of IV thrombolysis followed by IA thrombolysis (specialised centre)• IMS study (Interventional management of stroke) IMS study Investigators Stroke

2004 ; 35 ; 906-911

– IV TPA 0.5 mg/kg (60 mg max over 30 minutes) within 3 hours of onset, IATPA at site of occlusion to a total dose of 22 mg over 2 hours of infusion or till recanalization

– Symptomatic ICH 6.3% (NINDS 6.4%)– 3 monthly mortality lower (16%) but NS vs placebo (24%) and IV TPA of

NINDS group (21%). IMS group had significantly better outcome at 3 months compared to NINDS placebo group

Recommendation ( AHA / ASA / Adams et al Stroke 2007)• At present combination IV and IA TPA to restore perfusion cannot be

recommended outside the setting of a clinical trial (Class III Level B)

ENDOVASCULAR INTERVENTION

CLOT EXTRACTION

MERCI (Mechanical Embolus Removal in Cerebral Embolism TRIAL Smith WS Stroke 2007

i) MERCI device to extract thrombi from occluded intracranial vessels

ii) Rate of recanalization of MCA in MERCI was 60% - 68% vs 66% in PROACT II and 39% with IVTPA

iii) FDA approved

Recommendation (AHA / ASA / Adams et al; 2007)

MERCI device has FDA approval. MERCI device is a reasonable intervention for extraction

of intra-arterial thrombi, the utility of the device in improving outcomes after stroke is

unclear (Class II B, Level B)

Usefulness of other endovascular treatment is not established

STROKE UNIT MANAGEMENT

ANTICOAGULATION AND ACUTE ISCHEMIC STROKE

UNFRACTIONATED HEPARIN

• International Stroke trial Lancet 1997 ; 349 ; 1569 – 1581

– 5000 u/day vs 25,000 u/day, within 48 hours +_ Aspirin– Minor benefit in lowering early recurrence negated by increased bleeding

complication (No benefit even in AF)

• Swedish Trial – Roden Julling A I Intern med 2000 ; 248 ; 287 -291

– No benefit

• European trials- Camerlingo Stroke 2005 ; 36 ; 2415 – 2420 (within 3 hours)

No benefit

- Chemorro A Cerebrovasc Dis 2005 ; 18 ; 402 – 404

No benefit

LOW MOLECULAR WEIGHT HEPARIN

• Hong Kong trial Kay NEJM 1995 ; 333; 1588 – 1593Nadoparin x 10 days : No benefit

• Berg E Lancet 2000 ; 355 ; 1205 – 1210Dalteparin vs Aspirin : No benefit

• TOPAS Diener HC Stroke 2000 ; 32 ; 22 -29Certoparin : No benefit

• TAIST Bath DM Lancet 2001 ; 358 ; 702 -710Aspirin vs Tinazaparin : No benefit

• TOAST JAMA 1996 ; 279 ; 1265 – 1272IV Danaproid : No benefit, increased hemorrhage

• TRACE Woessror R Thromb Haemost 2004 ; 91 ; 690 – 693subcut Enoxaparin : No benefit

TOAST TRIAL

Recommendation (AHA / ASA / Adams et al Stroke 2007)

• Early administration of Heparin or LMWH were associated with increased risk of bleeding (Symptomatic HTN or systemic bleed). No benefit on reducing risk of early recurrence nor early neurological worsening. No benefit in subgroups with AF, VB stroke, Arterial dissection

• Urgent anticoagulation with the goal of preventing early recurrent stroke, halting neurological worsening or improving outcomes after ischemic stroke is not recommended for patients with AIS (Class III, Level A)

• Initiation of anticoagulation therapy within 24 hours of IV TPA is not recommended (Class III, Level B)

ANTIPLATELET AGENTS AND ACUTE ISCHEMIC STROKE

CAST (Chinese Acute Stroke Trial) collaborative group Lancet : 1997 ; 349 ; 1641 – 49

• IST (International Stroke Trial) collaborative groupLancet : 1997 ; 349 ; 1569 – 81

• NS reduction in death or disability with Aspirin initiated within 48 hours of AIS in either trial

• Modest but S benefit with combined results (7/1000 reduced early recurrence , 10/1000 reduced death, dependency)

• Use of Clopidogrel, Dipyridamole in the setting of acute stroke has not been adequately evaluated

COMBINATION ANTIPLATELET AGENTS• Aspirin – Clopidogrel has been used in ACS, with no significant evaluation in

AIS

SINGLE ORAL ANTIPLATELET AGENTS

Recommendations (AHA / ASA / Adams et al Stroke 2007)

• Oral administration of Aspirin (Initial dose of 325 mg) within 24 – 48 hours of stroke onset is recommended (Class I, Level A). New with addition of dose

• Aspirin should not be considered as substitute for IVTPA (Class III, Level B)

• Aspirin as adjunctive therapy within 24 hours of TPA is not recommended (Class III, Level A)

• Administration of Clopidogrel alone or in combination with Aspirin is not recommended (Class III, Level C)

• Outside the setting of clinical trials IV Antiplatelet Glycoprotein Iib/IIIa is not recommended (Class III, evidence B)

NEUROPROTECTIONNEUROPROTECTION

NEUROPROTECTION• Aim : Slow down or halt the ischemic cascade for a limited period of time allowing prolongation of

reperfusion therapy time window

• Trials OutcomeNimodepine Calcium channel blocker Not approvedFosphenytoin Na channel blocker Not approvedSelfolol NMDA antagonist No efficacy in phase III trialsTrilazed Lipid peroxidation inhibitor Worsened outcomeLubeluzole Ion channel and nitric Not approved

oxide blockerClomethiazole GABA agonists Phase III halted due to no

efficacyRepinotan 5HT1A receptor agonists Halted due to poor phase IIb

resultsONO2506 Astrocyte modulting Phase II trials unfavorableNXY – 050 SAINT 1 & 2 – no benefit

RECOMMENDATIONS (AHA / ASA / Adams et al; 2007)• No neuroprotective intervention can be recommended for stroke management

(Class III level A)

TEMPERATURE

• Increased body temperature in AIS (first 24-48hrs) is associated with increased morbidity and mortality secondary to increased free radical production (Hajat stroke 2000:31:410-414, Castillo stroke 1998, 29: 2455-2461)

• Fever secondary to cause of stroke (Infective endocarditis) or complications (Pneumonia, UTI)

• Lower body temperature by antipyretics or cooling device will logically improve neurological outcome (Dippel DW stroke 2001, 32:1607-12)

• Hypothermia has not shown any significant benefit

• Recommendations (AHA/ASA/Adams et al stroke 2007) Source of fever should be treated and antipyretics should be administered to lower temperature in febrile patients (class I , level C)

AIRWAY, SUPPLEMENTAL OXYGEN AND VENTILATORY SUPPORT

A) Supplemental oxygen

i) Routine supplemental oxygen not required for stroke patients (Ronning OM Stroke 1999 ; 30:2033-2037)

ii) Supplemental oxygen used for :

a) Hypoxia : SO2 < 95%

b) Reduced level of consciousness

c) Bulbar dysfunction

B) Elective intubation – Prognosis poor with 50% dead within 30 days of stroke (Bushnel CD Neurology 1999 ; 52; 1374-1381)

i) Increased ICP or malignant brain edema

ii) Poor airway – altered sensorium or bulbar dysfunction

iii) GCS < 8

C) Hyperbaric oxygen – No benefit except in symptoms secondary to air embolism (Rusynlek stroke 2003; 34; 571-574)

HYPERTENSION

• Caution in treating hypertension in AIS unless medical indication (aortic dissection, ARF, pulmonary edema, ACMI,HT encephalopathy)

• Recommendation (AHA/ASA/Adams et al stroke 2007)

• BP Target

– Nonthrombolysis : Sys >220, Dias >120 (class I, level C new recommendation)

– Thrombolysis : Sys >185, Dias >110

• Withold or reduce antihypertensive medication for 24- 48 hrs

• Hypotension – neurological deterioreation if Sys <100, Identify cause eg: Volume depletion, blood loss, aortic dissection, myocardial ischemia or arrhythmias

HYPERGLYCEMIA AND STROKE• Experimental evidence supports a causal relationship between hyperglycemia

and adverse outcome after stroke

• Baird TA Stroke 2003 ; 34 ; 2208 – 2214 – hyperglycemia (Blood sugar > 140 mg / dl) in 72 hours post AIS was associated with larger infarct on MRI and worse stroke outcome

• Metanalysis of 35 control trials of 8478 pts using GKI infusion – reduced mortality by 15%Malmberg J AM Coll Cardiol 1995 ; 26 ; 57 – 65

• GIST – UK Trial Gray, Lancet Neurol 2007 ; 6 ; 397 – 406Compared GKI vs NS in first 24 hours – No significant change in outcome

Recommendations (AHA/ASA/Adams et al stroke 2007)• Correct hyperglycemia > 140 mg / dl with desired level of 80 – 140 mg / dl

during 1st 24 hours (class II A level C)• No indication for intensive GKI infusion

GENERAL CARE

• Bed rest – Early mobilization when considered stable

• Frequent turning or alternative pressure mattresses

• Measures to avoid falls

• Nasogastric feeding if abnormal swallow test , impaired gag reflux, dsyphonia, cranial nerve palsy, high NIHS score, impaired cough

• Bedside swallowing test – 60 ml liquid, watch for cough, wet voice

• (Food trial Lancet 2005;365;755-772)No benefit of dietary supplements, Initiation of NG feeds within 7 days or later, NG feeds vs PEG

• Recommendation (AHA/ASA/Adams et al Stroke 2007) assessment of swallowing before starting or drinking is recommended (new)

DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM

• Pulmonary embolism accounts for 10% deaths post stroke • Pulmonary emboli arise from venous thrombi in paralysed limb or pelvis• Higher risk in older, prolonged immobilization, severe stroke

PREVENTION • Early mobilization• Anticoagulation

i) SC Heparin or LMWH (most effective)ii) No efficacy or safety difference in Heparin vs LMWH Counsell Cochrane

database syst review 2001;4;CD000119iii) Low dose warfarin for long term Ridher NEJM 2003;349;2164-67

• Aspirin also helpful though less effective Antiplatelet trialists collab; BMJ 1994; 308;235-246

• External compression stockings can be used if anticoagulation is contraindicated (Class IIa level B)

• IVC filter device if recurrant events despite anticoagulation or anticoagulation is contraindicated

DECOMPRESSIVE HEMICRANIECTOMY AND DUROPLASTY – FOR MALIGNANT MCA-INFARCT

Hemicraniectomy doubled the chances of survival from 29% to 78% - absolute risk reduction 48% (HS)

– Number to treat 2 to avoid 1 fatality

– 10 HC – 5 pts will escape death, at 1 yr 1 pt will have mild disability, 1 will have moderate disability and 3 will have moderate to severe disability

URGENTLY TRIAGE AND SHIFT TO STROKE ICU

Aspirin ?Aspirin ?

CT head vs multimodal MRICT head vs multimodal MRI

IV TPA < 4.5 hourIV TPA < 4.5 hour IA TPAIA TPAMERCI DEVICEMERCI DEVICE

(4.5 – 6 hr)(4.5 – 6 hr)

STROKE ICUSTROKE ICUCARE > 4.5 hr)CARE > 4.5 hr)

• General careGeneral care• AspirinAspirin• Heparin in DVTHeparin in DVT

preventive dosepreventive dose• Manage complicationsManage complications

DR VINEET SURI

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