Guides for the management of acute ischaemic stroke in KPJ Kedah and Kuching. Prepared br Dr. Ong Beng Hooi & Dr. Chai Chiun Hian.

1. 1
KPJ Kedah and Kuching Thrombolysis Pathway for Acute Ischaemic Stroke
1. Triage at A&E:
Eligibility for IV Thrombolysis
Ø Age ³ 18 yo (no age limit)
Ø Symptoms onset within 4.5 hours
Ø > 4 NIHSS < 25
Ø NIHSS 2-4 with isolated a/dysphasia, ataxia or hemianopia or with large
artery occlusion or significant penumbra
ALL Criteria Met
Proceed to thrombolysis pathway
Criteria Not Met
Standard Stroke Management
Urgent Contact and Arrangement
Contact Neurologist, Radiologist (Radiographer)
Initial Managements
1. Focus history to review inclusion/exclusion criteria (page 2)
2. Perform NIHSS score & focused physical examination
3. Record Hypocount (HGT): Treat if HGT < 4 mmol/L or > 20 mmol/L
4. Record BP if SBP> 185 mmHg or DBP> 110 mmHg
5. IV Access with 20G (pink) cannula or LARGER
6. Send blood for GP61P (remark urgent FBC/BUSE/CREAT), PT/PTT/INR,
Group save hold 2 units of pack cells
7. ECG
8. Record Weight (or estimate)
9. Urgent CT brain +- CT Angiography +- CT Perfusion scan or
GRE/DWI/MRA/MRP (6 min)
Post CT Managements
1. CT brain to be reviewed by radiologist or neurologist for any contraindications
for thrombolysis
2. Neurologist to make decision on whether to proceed with thrombolysis
3. Patient’s consent obtained
4. BP must be < 185/110 mmHg before thrombolysis
5. IV alteplase to be given at A&E or ICU, give with IV pantoprazole 40 mg stat
6. Patient with Large Vessel Occlusion (LVO) to consider mechanical
thrombectomy
7. Patient admit to ICU or HDU

2. 2
2. Eligibility
• Age ³ 18 years (no upper age limit)
• Symptoms onset within 4.5 hours
• >4 NIHSS < 25
• NIHSS 2-4 with isolated a/dysphasia, ataxia or hemianopia or with large artery occlusion
or significant penumbra
• ASPECT score
o 7-10 (Early ischaemic changes)
o <7 (Early ischaemic changes (EICs) > 1/3 on CT brain)
§ reconsideration for thrombolysis if significant penumbra assesses by
CTP/MRP (core > 70-100 cc) or good collateral score (CTA) (>3)
§ contraindicated for thrombolysis if clear cut > 1/3 infarction
o 9-10 and < 3 hours: For Elderly patients (>80 years)
• Haemorrhage excluded on Neuro-imaging

3. 1
Acute Ischaemic Stroke
< 4.5 hours > 4.5 hours
CTP or MR perfusion diffusion
assess infarct core
& futility of recanalization (PENUMBRA)
Non- LVO
LVO
(Large Vessel Occlusion)
*NIHSS > 9 predictive of LVO
ASPECT ³ 7
Any NIHSS
ASPECT ³ 7 ASPECT < 7
IV
Thrombolysis
EVT
(Endovascular
Thrombectomy)
EVT
(Endovascular
Thrombectomy)
IV
Thrombolysis
IV
Thrombolysis
Non- LVO
(Wake up stroke
Or SUSO
or 4.5-9 hours)
LVO
(Proceed >9 hours
Up to 24 hours
Post stroke)
EVT
(Endovascular
Thrombectomy)
Ó Dr Ong Beng Hooi
* NIHSS predictor for LVO
>9: within 3 hours
>7: within 3-6 hours
>4: after 6 hours
(>12: related to central occlusion)

4. 4
3. Contraindications & Precautious situations
3.1. Contraindications
• Major surgery in last 14 days
• Minor surgery within past 10 days, including liver & kidney biopsy, thoracocentesis
• GI or urinary tract bleeding in last 21 days
• Symptoms suggestive of subarachnoid bleed (Even if CT brain clear)
• Systolic BP> 185 mmHg or Diastolic BP > 110 mmHg unresponsive to medical treatment
• Coagulopathy: INR > 1.7 or aPTT> 1.5 x normal, or platelet count < 100 000
(rt-PA maybe started before PT/PTT and platelet count are known if there is no history
of alcohol abuse, not ESRF, no heparin/warfarin use, no history of Antiphospholipid
syndrome, no Liver disease/haematological disease/ metastatic cancer, no bleeding of
any type within the last 1 month)
• High pre-morbid dependency Modified Rankin Score ≥ 4
• Serious trauma (non head) within preceding 14 days
• Lumbar puncture or arterial puncture at non-compressible site in last 7 days
• Presentation consistent with infective endocarditis
• Active bleeding or acute trauma (fracture) on examination
• Stroke known or suspected to be associated with aortic arch dissection
3.2. Precautious Situations
• Use of anticoagulation in last 24 hours: Heparin or NOACS, Warfarin (Refer 8.1)
• Stroke after cardiac catheterization (Refer to 8.2)
• Wake up stroke or 4.5-9 hours, to assess penumbra with CTP or MR Perfusion Diffusion
(Refer 8.3)
• Acute Myocardial infarction (MI) in the last 3 months (Refer 8.4)
• Hypoglycaemia (< 4 mmol/L)
• Cerebral tumour, AVM/cavernoma or aneurysm
• Previous history of Intracranial bleed
• Cerebral amyloid angiopathy or multiple cerebral microbleeds
• Intracranial cerebral artery dissection
• Diabetic haemorrhagic retinopathy or other haemorrhagic ophthalmic condition
• Haemostatic defects including those secondary to severe hepatic or renal disease
• Pregnant (up to 10 d postpartum) or nursing mother
• Rapidly improving NIHSS
• Seizure at onset of symptoms (Not exclusion if MRI/A with DWI confirms ongoing
cerebral ischaemia)
• Left heart thrombus
• Repeat IV Thrombolysis or IV Thrombolysis after recent Ischaemic stroke (Section 9.6.1
and 9.6.2)
• Treatment from 3 to 4.5 hours: Additional relative exclusions (where the risk/benefit
raio is less clear) are Age > 80 years, oral anticoagulant use regardless of INR, severe
stroke (NIHSS > 25) and/or a combination of both previous stroke and Diabetes mellitus

5. 5
4. Patient Consent
• Informed patient this is the standard treatment for acute stroke that meet inclusion and
exclusion criteria
• If patient is lacking capacity to give their consent, then should be discussed with their
next-of-kin
• Patients should be informed:
o 1 in 3 chance of improvement
o 1 in 20 chance of bleeding
o 1 in 100 chance of death
5. IV Thrombolysis
5.1 Alteplase Administration
• Alteplase is the only agent licensed for thrombolysis of ischaemic strokes
• Administer 0.9 mg/kg body weight up to a maximum of 90 mg
• 10% of total dose as an IV bolus over 2-3 minutes.
• The remainder 90% should be administered as an infusion over 60 minutes.
5.2 Tenecteplase Administration
• It may be reasonable to choose tenecteplase (single IV bolus of 0.25 mg/kg, maximum 25
mg) over IV alteplase in patients without contraindications for IV fibrinolysis who are
also eligible to undergo mechanical thrombectomy.
Additional Informations on Section 5. IV Thrombolysis
o Lower dose alteplase:
§ IV Thrombolysis with alteplase 0.9 mg/kg vs 0.6 mg/kg over 1 hour
(ENCHANTED trial)
•
o Tenecteplase as an alternative to Alteplase
§ Compared to Alteplase: Tenecteplase has higher fibrin affinity, greater resistance
to PAI-1 (Plasminogen activator inhibitor-1) and longer half-life (allowing for a
single IV bolus instead of 1-hour infusion), low effects on general haemostasis,
last 8 hours vs 5 min in Alteplase
§ Tenecteplase 0.4 mg/kg is safe vs Alteplase in AIS (NOR-TEST)
§ In LVO cohort: Tenecteplase 0.25 mg/kg (max 25 mg) achieved 22%
recanalization rate vs 10% in Alteplase at 60 min. However almost same
recanalization rate at 90 min.
§ Alteplase Early Recanalization rate is < 50% vs Tenecteplase >50%;
§ 90 days mRS favouring Tenecteplase :Tenecteplase+Thrombectomy (mRS 0-2:
63%) vs Alteplase+Thrombectomy (mRS 0-2: 50%)

6. 6
6. Neuroimaging
ASPECT SCORE
• Size of infarct (objective)
• 10 points
• Can be used up till 12 hours
• Non-contrast CT Brain ASPECT score has good correlation with CTP/DWI for Follow-up Infarct Volume
(FIV) if stroke onset is <4.5 hours (for IV thrombolysis) and <9 hours (for EV Thrombectomy).
• Low ASPECT score can still benefit from EV Thrombectomy if CTP show significant penumbra (10%)
Non-contrast CT ASPECT MRI DWI ASPECT
IV Thrombolysis • Score ³8 (favourable) • Score ³7 (favourable)
EV Thrombectomy • Score 6 – 10 (favourable) • Score 5 – 10 (favourable)
• Score 4 – 6:
o correlation with core volume is modest
o 100 ml – 70 ml
• Score 0 – 4:
o Benefit of EVT is controversial
Collateral Scores
• Collateral circulation is a key determinant of ischemic core and penumbra. Better collaterals are
associated with smaller ischemic core volumes and larger mismatch ratios on CT perfusion.
• The collaterals can be better estimated by multiphase CTA compared with single-phase CTA.
• A collateral score of > 3 on multiphase CTA best identifies patients with target mismatch on CT
perfusion and predicts 90-day mRS score of 0-2.
mCTA Perfusion based collateral assessment (CTP/MRP)
1. AC-CS > 3
(85% sensitive, 70% specific)
2. BATMAN score > 3
(70% sensitive and 60% specific) or PC-CS
Hypoperfusion Intensity Ratio (HIR): (Refer CTP/MRP)

7. 7
CTP/MR perfusion diffusion scan
• Generally indicated for out of standard period window to define the penumbra benefit from
intervention (ratio core to penumbra is 1.2, core volume <70 cc) up to 16-24 hours (correlate with good
functional outcome) or low ASPECT score
• Early CTP within time window (< 4.5-hour rtPA or 9 hours for thrombectomy) is indicated for
o Collateral score (perfusion)
o Pseudo Low ASPECT
o Stroke Mimic
Non-LVO LVO
• Indicated for patient
o Presented >4.5 hours or
o Wake Up Stroke (WUS) or
o Stroke of Unknown Symptom
Onset (SUSO)
• To determine the benefit of IV Thrombolysis
• Indicated for patient
o Presented >9 hours
o Drip & Ship for EVT centre (HIR)
Hypoperfusion Intensity Ratio (HIR)
• to assess benefit vs futility
(HIR >0.5)
§ predict core growth of >5 ml/hr
(sensitivity 83%, specificity 85%)
§ 50% repeated scan will show infarct
core >70 cc & no mismatch
o Low ASPECT <7
o Permeability Surface (PS) of Deep MCA
Teritory for the risk of HT (rPS > 2.89)
• To determine the benefit of EV Thrombectomy
Pitfall: Early CTP may overestimate the infarct core, called Ghost Infarct.
o About 40% will get > 10 ml Ghost Infarct
o About 10% of patients may be denied of EV Thrombectomy
Collateral status
• Affects the onset to reperfusion time window for good outcome (time-penumbra relationship)
• Penumbra salvage & infarct growth less time dependent & more of a measure of collateral status
(can persist up to 48 hours)
Slow Progressors of LVO:
• <30% of AIS with LVO with good collateral presented with slow infarct growth over time
Rapid Progressors of LVO:
• < 50% of AIS with LVO presentation
• About 40% with poor outcome despite good reperfusion within 3-6 hours
Collateral Collapse mechanism:
• Poor Collateral back-filling of the pial macrovasculature may just be a secondary consequence of
increasing periphera/distal (microvascular) resistance which maybe inevitably caused during
progressive infarction by molecular and cellular reason.
Ischaemic Tolerability:
o Follow-up Infarct Volume (FIV)= CBS (Clot Burden Score) + CS (Collateral Score)
o RtPA = NIHSS-ASPECT/PERFUSION-DIFFUSION MISMATCH x CBS x CS
o EVT = NIHSS-ASPECT/PERFUSION-DIFFUSION MISMATCH x CS

8. 8
AIS
<6 hours >6 hours
CT/CTA
ASPECT <7
DWI/GRE/
FLAIR/
MRP & MRA
ASPECT ³7
+ CTP/MRP
Thrombolysis
Or
EV Thrombectomy (LVO)

9. 9
7. Predictors of poor early recanalization (ER)
• LVO – thrombus length >8 mm
• Poor collateral
• Tandem occlusion
• High NIHSS
• Hyperglycemia
• Branch arterial disease (BAD)
• Severity of ischaemia, HIR if thrombus length <14 mm
8. Hypertension Management
• BP must be < 185/105 mmHg prior to administering Alteplase, and must be maintained at this
level up to 72 hours after thrombolysis:
• BP must be < 160/90 mmHg after Endovascular thrombectomy (EVT). However, permissive
hypertension is allowed for partial or non-recanalize stroke but must be < 180/105 mmHg).
For rapid BP control:
1. If BP is raised on initial assessment then apply a 5mg GTN Patch.
2. If BP remains high administer I0mg IV Labetalol over 1-2 mins. (Refer page 4) This can be
repeated after 10 minutes if required. Up to total dose of 150 mg.
3. If BP is unresponsive to Labetalol boluses or if Labetolol is contra-indicated (e.g Asthma, CCF,
heart block) then commence a GTN infusion at a rate 3 ml – 15 ml/hour (5-25 mcg/minute or
300-600 mcg/hour). (Refer page 5)
4. If BP remains raised despite above measures then contraindicated for thrombolysis
administration.

10. 10
I) IV LABETOLOL (KPJ Kuching: 25mg/5ml ampoule)
• IV Labetolol is useful in hypertensive crises (including severe hypertension when planning
thrombolysis for ischaemic stroke) as it has predictable effects, low risk of overshoot, and short
half-life.
• Indications: (Thrombolysis)
o Systolic BP > 180 mmHg
o Diastolic BP > 105 mmHg
• Contraindications:
o Bronchial Asthma
o Overt Cardiac failure
o Severe Bradycardia
• Dosage & administration
i) Bolus
o IV injection (push) over 1 – 2 minutes
o Usual dose: 10 mg, repeated every 10 minutes
o Ampoule: 25mg/5ml, so 10 mg is 2 ml
o Maximum dose: 150 mg
ii) Infusion
• Mix 25mg/5ml ampoule Labetolol in 20ml D5%, so 1ml=1mg Labetolol, commence at 20
ml/hour (20 mg/hour) and titrate up to 150 ml/hour (150mg/hour) until BP control. To
start oral medication and stop infusion once achieved BP control
iii) Excessive bradycardia:
• IV atropine 0.5-2mg in divided doses of 0.5 mg
• Monitoring BP
o For severe hypertension, BP should be checked 10 minutely until treatment is
completed, then 15 minutely for the next 2 hours, then 30 minutely for the next 6 hours,
then hourly until 24 hours.

11. 11
II) IV GTN (KPJ Kuching: 10mg/10ml ampoule)
Administration Guidelines
• GTN for Injection is a concentrated potent drug, which must be diluted in sterile 5% glucose
or sterile 0.9% sodium chloride prior to its infusion.
• Intravenous GTN can only be administered in the High Acuity Areas including ICU / HDU, CCU
Operating Rooms/Recovery and the Emergency Department where patients can be cardiac
monitored.
• The infusion once prepared is stable for 24 hours and should be replaced with a new
infusion preparation every 24 hours.
IV Infusion via volumetric pump:
(Concentration of 50mg / 500ml = 100micrograms/Ml)
Preparation
• Dilute GTN prior to intravenous infusion (do not use GTN for direct intravenous injection).
• Avoid skin contact with concentrated solution when preparing infusion.
• Aseptically withdraw and discard 10mL from a 500mL glass IV bottles / non-PVC fluid bag of
5% glucose.
• Add five GTN 10mg/10mL ampoule to 450mL of 5%glucose giving a final concentration of
50mg / 500ml = 100micrograms/mL
OR: One GTN 10mg/10ml ampoule to 90 ml of 5%glucose giving a final concentration of
10mg/100ml = 100micrograms/ml
NB: Concentration may be increased but must not exceed 400 micrograms/mL
• GTN absorbs into many surfaces - to avoid absorption, glass IV bottles / non-PVC fluid bags
and appropriate non-PVC giving sets must be used.
Administration
• Commence at 5 -10microgram/minute (300 -600micrograms /hour = 3 - 6ml/hour)
delivered through an infusion pump.Titrate infusion according to pain response and to
maintain blood pressure in the target range.
• Usual dose range is 5 micrograms to 25 micrograms/minute (3mL to 15mL/hour).
• If systolic blood pressure falls below 90mm Hg, cease the infusion. If blood pressure does
not begin to increase within 5 minutes notify medical officer.
• Monitor blood pressure continuously via arterial line or every 2-3 minutes (if using NIBP).
• Continue infusion at dose previously tolerated if blood pressure is stable.
Weaning:
• Decrease rate by 3mL/hour (300 microgram/hour) every five minutes while maintaining
desired hemodynamic parameters.
• Discard any unused GTN infusion after 24 hours and prepare new infusion if required.
KPJ GTN:
i) 10mg/10ml ampoule mix with 30 ml Normal saline = 4mcg/min (1ml/hour)
ii) 50mg/10ml ampoule, take out 12.mg/2.5 ml add with 47.5 ml of normal saline
= 4mcg/min(1ml/hour)
Commence at 1ml/hour, titrate between 1 to 5ml/hour（4 mcg to 20 mcg/minute）

12. 12
9. Thrombolysis in special conditions:
9.1 Patients on Anti-coagulants
• On warfarin: INR < 1.7 can be given thrombolysis
• On Unfractionated Heparin: not contraindication if aPTT < 1.2 normal
• On LMW heparin (eg enoxaparin): in the last 24 hours is an ABSOLUTE
contraindication
• On Direct Thrombin Inhibitors (Dabigatran): Can use Antidote: Praxbind (Idaruxizumab),
or a normal Thrombin time and aPTT
• On anti-Xa agents (Apixaban, Rivaroxaban, Edoxaban): Contraindicated until at least 24
hours has elapsed since their last dose
Specific treatment algorithm for tPA delivery in AIS patients pretreated with Dabigatran
Acute ischaemic stroke within 4.5 hours after symptom onset in Dabigatran treated patients
Determine time of last intake of Dabigatran
Less than 24 hours or 48
hours if GFR < 50 ml/min
More than 24 hours or 48
hours if GFR > 50 ml/min
Time
unknown
Administration of 5 gram Idarucizumab
(2x2.5 g/50 ml) intravenously as two
consecutive infusion over 5 to 10
minutes each or as a bolus injection
Check aPTT, dTT, TT
Prolonged Not prolonged
tPA 0.9mg/Kgr

13. 13
9.2 Wake Up Stroke (WUS) or
Stroke of Unknown Symptom Onset (SUSO)
• Wake up stroke within 3 hours:
§ NC CT brain ASPECT >7 without LVO IV thrombolysis
• Wake up stroke or 4.5-9 hours, to assess penumbra with CTP or MR Perfusion
Diffusion and for EV Thrombectomy if:
§ Perfusion lesion-ischaemic core mismatch ratio >1.2
§ Absolute difference in volume >10 ml
§ Ischaemic core <70 cc
• WUS: (Best Evidences)
§ WAKE-UP trial: Barreto et al 2016: Patients with WUS with NCCT Brain
ASPECT given IV thrombolysis within 3 hours from awakening showed
to be safe, with 53% patients achieved mRS score 0 or 1 at 3 months.
§ DUST trial: Dankbaar et al 2018: Patients with WUS vs patients who
arrive in hospital within the time criteria for IV thrombolysis and EV
thrombectomy showed only minor differences between clinical and
imaging characteristics. (75% of WUS >4.5 hours were similar with stroke
of known onset <4.5 hours, while 54% of WUS with LVO >6 hours were
eligible for EV thrombectomy)
§ WAKE-UP trial: Thomala et al 2018: Patients with SUSO with mild
stroke (median NIHSS 6) given IV thrombolysis guided by MRI mismatch
between DWI and FLAIR showed better functional outcome (53.3%) at 3
months vs placebo (41.8%), with more intracranial haemorrhages in
treatment group vs placebo (2.0% vs 0.4%).
§ EXTEND trial: Henry Ma et al 2019: Patients presented with ischaemic
stroke between 4.5 and 9.0 hours or WUS, with salvageable brain tissue
based on automated penumbra imaging using CT perfusion or MR
perfusion (perfusion lesion-ischaemic core mismatch ratio >1.2 an
absolute difference in volume >10 ml and ischaemic core <70 ml), given
IV thrombolysis showed good functional outcome at 3 months vs control
(35% vs 29%), with more cases of symptomatic intracranial haemorrhage
in treatment group vs control (6.2% vs 0.9%). Limitation: early
termination of study and large percentage (>70%) of LVO patients.
§ DAWN trial: Nogueira et al 2018: Patients presented with ischaemic
stroke and LVO (proximal MCA or ICA) between 6-24 hours, with
clinical-core mismatch between clinical deficit and infarct volume (<21 ml
in ³80-year-old vs <31 ml in <80-year-old), showed better disability
outcome at 90 days with thrombectomy plus standard care than standard
care alone. Symptomatic bleeding between thrombectomy group (6%)
were similar with control group (3%).

14. 14
§ DEFUSE 3 trial: Albers et al 2018: Patients presented with ischaemic
stroke with LVO (proximal MCA or ICA) between 6-16 hours with CT
perfusion or MR diffusion and perfusion scan showed viable ischaemic
tissue (radiological mismatch) using RAPID software (initial infarct
volume (ischaemic core) <70 ml, a ratio of volume of ischaemic tissue to
initial infarct volume of ³1.8, and an absolute volume of potentially
reversible ischaemia (penumbra) of ³15 ml), endovascular thrombectomy
plus standard medical therapy resulted in better functional outcomes than
standard medical therapy alone (45% vs 17%). No significant symptomatic
intracranial haemorrhage between thrombectomy group (7%) vs control
group (4%).
§ THAWS trial: Koga et al 2019: Patient with SUSO given IV thrombolysis
with rTPA at 0.6 mg/kg in Japan guided by MRI mismatch between DWI
and FLAIR, showed no evidence of benefit but also no evidence of harm
(neutral result). Trial was terminated earlier due to positive WAKE-UP
trial results.
• SUSO: (Best Evidence)
§ MR WITNESS trial: Schwamm et al 2018: Patients presented with SUSO
without LVO, selected by quantitative MRI diffusion-FLAIR mismatch
(qDFM) and given IV thrombolysis within 4.5 hours of symptom
discovery but beyond recommended time windows is safe. Further trial is
required to test the efficacy using qDFM.
9.3 Stroke after Cardiac Catheterization
• Stroke risk post cardiac catherization: 0.1-0.7%
o Elective: 0.3%
o Emergency: 0.6%
• Silent Neurological Injury (SNI): 13-22%
• Majority (80%) occur within 48 hours
• Anterior circulation stroke (58%) vs Posterior circulation stroke (52%)
• In-hospital mortality: 32%
• IV thrombolysis can be given if <4.5 hours
o Suggested lower dose tPA of 0.6 mg/kg
o Heparin effect reverse by Protamine sulphate 50 mg within 5 minutes.
(If no Protamine sulphate: wait for 50-90 min due to half-life of Heparin)
• Endovascular Thrombectomy is the best option if >4.5 hours or Intra-arterial
thrombolysis within 6 hours

15. 15
9.4 Post myocardial infarction (MI) with Acute Ischaemic Stroke
(Cardio-Cerebral Infarct CCI)
• Rate:
o Simultaneous (0.009%)
o Concurrent (0.6%)
o Metachronous/Post MI (0.9%) in the first 30 days (3x risk within first
month)
• Risk of CCI is the highest in first 30 days post MI, and remain high risk up to 12
weeks post MI
• Mortality of CCI: 52% (vs MI alone 37%)
• Mechanism: LV clot (15%) or Atrial Fibrillation or Others (Insular Stroke)
• IV Thrombolysis with rTPA for Acute MI:
o rTPA within 24 hours: Risk of myocardial rupture is 1.6% and cardiac
tamponade 1-8% (non thrombolysed MI 1-5% risk of cardiac rupture)
o risk of cardiac rupture is low if given within 12 hours
• IV Thrombolysis with rTPA for CCI:
o Relative contraindication if given within 3 months due to
§ Risk of myocardial rupture 1% incidence with the highest risk in
the first week post MI, mostly within 24 hours
§ LV clot fragmentation and embolism
§ Anticoagulation
o Simultaneous CCI: IV thrombolysis up till 4.5 hours from stroke onset
with cerebral dose
o Concurrent CCI: IV thrombolysis up till 4.5 hours from stroke onset
(provided post MI within 24 hours)
o Post MI after 24 hours:
§ Contraindicated for IV thrombolysis up till 7 weeks. EVT will
be a viable option
§ Exception: Treated STEMI/ Right/ Inferior STEMI/
NSTEMI/Severe Stroke: (Risk of myocardial rupture 1% vs
Severe Stroke)
o High risk for cardiac rupture:
§ Old age (>70 years)
§ Extensive Anterior Transmural Infarction
§ Female sex
o Echocardiogram to guide treatment:
§ To assess the severity/extensiveness of infarcted myocardium
§ Successful treated MI with minimal myocardial injury can always
be treated with rTPA without fear of myocardial rupture
o EVT is a better option if available

16. 16
9.5.1 IV Thrombolysis for elderly (Octagenarian-80 & Nanogenarian-90)
• About 30% of AIS patients are elderly ³ 80-year-old
o Over 2/3 of patient ³ 80 with NIHSS 14 die or dependence by 90 days despite
thrombolysis
• Favourable outcome:
o Octagenarian (25-30%) vs patient <80 (40%)
o Nanogenarian (14%)
o Octagenarion with LVO (16% with rTPA)
• Mortality rate:
o Octagenarian (17%) vs patient <80 (12%)
o Nanogenarian (45%)
o Octagenarion with LVO (22% with rTPA)
• Age-Adjusted Core Selection Paradigm: Age dependent ASPECT adjustment is
needed to achieve good outcome
o Age & FIV predict outcome
o FIV threshold reduced with increasing age:
§ Aged < 70: 49 ml
§ Aged 70-79: 32.5 ml
§ Aged ³ 80: 15.2 ml
o ASPECT 9-10 with FIV < 16 ml is the best predictors of good outcome in old
age vs FIV < 40 ml as good predictor for younger patients
o NCCT ASPECT 9-10 (<4.5 hours) achieve reperfusion will get good outcome
• Octagenarian and Nanogenarian patients have higher effect with reperfusion therapy
(either IV thrombolysis or EVT) compared to patient <80
• Intracranial haemorrhage (ICH) rate:
o Octagenarian (5.7%) vs patient <80 (4.4%) but p value not significant
o Nanogenarian (13%)
• Elderly age is not a barrier for reperfusion therapy but better selection criteria are
needed
• Asian and Western elderly patients have similar outcome, mortality and bleeding rate
9.5.2 EV Thrombectomy for elderly(Octagenarian-80 & Nanogenarian-90)
• Pre-stroke mRS: Elderly ³ 80 (58%) vs patient (20<80%)
• Outcome with ASPECT 8 or more (in Elder patients ³ 80)
o EVT (30-35%) vs rTPA (16%)
o Overall Mortality rate (20-25%)
o Recanalization rate: same as younger patients
o No observed differences in age-dependent effect on clinical outcome for EVT
vs rTPA
• Octagenarian and Nanogenarian patients should opt for EVT if possible

17. 1
Ó Dr Ong Beng Hooi
Acute Ischaemic Stroke
In Elderly (>80)
< 3 hours 3 - 4.5 hours
LVO
(Large Vessel Occlusion)
*NIHSS > 9 predictive of LVO
Non- LVO
ASPECT 8-10
EVT
(Endovascular
Thrombectomy)
ASPECT 9-10
* NIHSS predictor for LVO
>9: within 3 hours
>7: within 3-6 hours
>4: after 6 hours
(>12: related to central occlusion)
IV
Thrombolysis
Non- LVO LVO
CTP or MR perfusion diffusion
assess infarct core
& futility of recanalization (PENUMBRA)
EVT
(Endovascular
Thrombectomy)

18. 18
9.6.1 Re-administration of IV Thrombolysis in AIS
• AHA recommended against repeat IVT within 90 days
• Median inter-IVT interval 30 days (13-50 days) with good outcome 47%
• Another series from 3 hours to 2280 days
• Caution: IV tPA-induced “early fibrin degradation coagulopathy” improves in 36
hours and administering IV tPA for the second time after 36 hours is thought to be
safe
• The increase in INR following IV tPA:
o Peak in 3-6 hours
o INR levels:
§ 10% of patients: 1.1 – 2
§ 1.5% of patients: > 2
o In the first 36 hours post IV tPA, recheck the aPTT, INR, D-dimer and
Fibrinogen level to exclude systemic fibrinolysis
o Standard thresholds for IV tPA should be used:
§ INR < 1.7
§ aPTT < 40
§ D-dimier < 2 nmg/dL
§ Fibrinogen > 100 mg/dL
9.6.2 IV Thrombolysis in AIS after recent Stroke
• 25% of Ischaemic stroke is recurrent
• AHA recommend against repeat IVT within 3 months or (follow Post MI
evidence 7-8 weeks)
• IST-3 recruited previous stroke after 14 days
• Leukoaraiosis is considered risk of increased post rtPA bleed at occlusion site
• Should only be considered individually based on Size of the lesion and Severity of
the neurological deficit
• Important factors for decision making includes: Time interval between infarction,
localization, volume and nature of the infarction
• Generally, increased risk of ICH 2.7 – 5.9% (statistically not significant in SITS-
EAST)
• In TIA, resetting the clock within 24 hours (definitely after 72 hours) with 33 –
58% achieved good outcome still with rtPA increase HT 17%

19. 19
10. Anaphylaxis
• Uncommon and can occur after IV alteplase.
• Clinical features:
o Urticarial rash
o Bronchospasm
o Angioedema
o Shock
• If anaphylaxis is suspected:
1. Stop infusion immediately
2. Urgent medical review as of Advanced Life Support Guidelines
3. Administer 1:1000 adrenaline 0.5 – 1 ml subcutaneous (SC) depending on
severity of the reaction
4. IV hydrocortisone 200 mg stat
5. IV Piriton (Chlorpheniramine) 10 mg stat
6. IV fluid challenge with 500 ml – 1 L of normal saline if in shock or hypotension
7. Inform critical care team
11. Post Thrombolysis
Post Thrombolysis Managements
8. All patients should be managed in ICU/HDU
9. Head chart, GCS and BP checks every 15 min for 2 hours, every 30 min for 6
hours, then hourly for 16 hours.
10. Maintain SBP < 180 mmHg, DBP < 105 mmHg (refer page 7)
11. Repeat NIHSS at 2 hours and at 24 hours
12. Avoid urinary catheter, NG tubes, IM injections, arterial puncture, central lines
for 24 hours, unless very necessary
13. Anti-platelet and Anti-coagulation should not be given within the first 24 hours
14. Repeat CT Brain in 24 hours, or for any neurological deterioration

20. 20
12. Mechanical Thrombectomy
• Patient with large arterial occlusion causing a disabling stroke (NIHSS>6) should be
considered for combination IV thrombolysis and mechanical thrombectomy, and to be
referred to center with Interventional Neuro-radiologist service
• If there is a contra-indication to thrombolysis but not mechanical thrombectomy then
a referral should be considered
• Mechanical thrombectomy can be performed in patient who had last been known to
be well 6 – 24 hours earlier and who had mismatch between clinical deficit and
infarct.
• Mechanical thrombectomy when compared to IV thrombolysis, the NNT is 2.6 to
achieve
o Reduction of > 1 points on mRS difference by 20% (46% vs 25%)
o Reduction of mortality by 10%
o Equal rate of Intracranial bleed (5-6%)
• Endovascular Thrombectomy is preferred option (mainly LVO) for:
o Proximal ICA/M1 or long thrombus length >8 mm occlusion
o Coagulopathies or INR >1.7
o END after mild stroke with or without IV thrombolysis
o Tandem occlusion
o Post MI or Post cardiac catheterization ischaemic stroke
o Severe Stroke (ASPECT <7)
o LVO stroke >4.5 hours
IV Thrombolysis + EVT EVT Alone
Efficacy 54% 42%
90 Days mortality 36% 25%
Intracranial Haemorrhage Similar
Cost Higher Lower
13. Blood pressure management in Acute Stroke:
a) Thrombolysis:
o Aim BP <180/105 mmHg up to 72 hours
o SBP 130-140 mmHg is safe but no benefit
b) Without thrombolysis:
o < 220/120 mmHg
c) Thrombectomy:
• <160/90 mmHg
• Permissive hypertension is allowed for parital or non-recanalize stroke <
180/105 mmHg

21. 21
d) Intracranial Haemorrhage
o <140/90 mmHg within 24 hours
o Every 10-mmHg reduction increase independence by 10% but no extreme BP
reduction >60 mmHg within an hour (which is harmful)
i) SBP: 180-230 mmHg
Or DBP: 105-120 mmHg (2 or more readings, 5 min apart)
o IV Labetolol dilution: Mix 25mg/5ml ampoule Labetolol into 20 ml D5%
(so 1 ml = 1 mg Labetolol)
o IV labetolol 10 mg over 1-2 min. Repeat or double as necessary every 10
min up to total dose of 150 mg
o Alternatively, start IV labetolol infusion at 20 mg/hour and titrate upward
to a maximum dose of 150mg/hour
o Monitor BP every 5 min during treatment and observe for development of
hypotension and bradycardia
ii) SBP > 230 mmHg
Or DBP: 121 – 140 mmHg (2 or more readings, 5 min apart)
• IV Labetolol 20 mg over 1 -2 min AND start a continuous IV labetolol
infusion at 40mg/hour, and titrate to maximum of 150mg/hour
• May give additional IV boluses of 20-40 mg over 1-2 min during infusion
every 10-15 min as needed
• Monitor BP every 5 min during treatment and observe for development of
hypotension and bradycardia
• IF BP not controlled:
o ADD IV nicardipine as a continuous infusion of 5mg/hour, titrate
upward until maximum of 15mg/hour
iii)DBP > 140 mmHg (2 more readings, 5 – 10 min apart)
• Start IV sodium nitroprusside (with thiosulfate buffer) at 0.5 ug/kg/min
IV, and titrate to a maximum of 5 ug/kg/min (doses up to 10 ug/kg/min
maybe used for brief periods of < 30 min)
• Monitor BP every 3-5 min, observe for hypotension
• Try to wean patient to a LABETOLOL and/or NICARDIPINE IV
drip within 24 hours (to avoid cyanide and thiocyanate toxicity)
Note: An arterial line is recommended to monitor BP during prolonged labetolol
infusions, and is necessary during prolonged nitroprusside infusions.
Risk of bleeding secondary to arterial puncture must be weighed against the possibility
of missing dramatic changes in pressure during the infusion.

22. 22
14. Bleeding risk after thrombolysis
• ICH risk score for IV thrombolysis:
1. Haemorrhage After Thrombolysis (HAT) score:
History of DM or initial glucose >11.1 mmol/L No
(0)
Yes
(+1)
Pre-tPA NIHSS <15
(0)
15-20
(+1)
>20
(+2)
Easily visible hypodensity on initial head CT No
( 0)
Yes, <1/3 of MCA territory (+1)
Yes, >1/3 of MCA territory (+2)
Total score
HAT score Risk of symptomatic
ICH
Risk of fatal ICH
1 5% 3%
2 10% 7%
3 15% 6%
4
44% 33%
5
2. SEDAN score for post-tPA Haemorrhage
Blood sugar
<8.1 mmol/L ( 0)
8.1 – 12.0 mmol/L (+1)
>12.0 mmol/L (+2)
Early infarct signs on
initial CT brain
No (0) Yes (+1)
Hyperdense cerebral
artery sign on initial CT
No (0) Yes (+1)
Age >75 No (0) Yes (+1)
NIHSS ³10 No (0) Yes (+1)
Total score
SEDAN score Risk of symptomatic ICH (ECASS-II definition)
0 1.6%
1 3.3%
2 5.4%
3 8.8%
4 12.3%
5
16.9%
6

23. 23
• Suspect Intracranial bleeding if:
o Neurological deterioration (GCS drop 2 or more, increase NIHSS of 4 or
more)
o New headache
o Acute rise in BP
o Nausea and vomiting
• Extracranial bleeding is not obvious, but suspect if:
o Drop in BP
o Signs of shock
o Evidence of blood loss
• IF bleeding is suspected:
o Stop IV alteplase infusion
o Urgent CT brain
o If suspected extracranial bleeding, urgent CT chest or abdomen or
endoscopy
• Urgent FBC, PT/PTT/INR, fibrinogen, Group and crossmatch
• Prepare for administration:
o 6-8 units of cryoprecipitate containing Factor VIII
o 6-8 units of platelets
IF NO ICH: DO NOT RESTART IV Alteplase
IF ICH:
• IV Tranexamic acid 1g in 100 ml Normal saline over 10 min
• Obtain fibrinogen results, if fibrinogen result < 1.2 to give cryoprecipitate
• Give cryoprecipitate 6-8 units and platelet 4 units
• Repeat fibrinogen level after 1 hour
• Consider IV Tranexamic acid infusion (1 g in 250 ml Normal saline infusion over
8 hours)
• Consult Consultant Haematologist & Neurosurgeon
• Consider 2nd
CT brain to assess progression of ICH
Other Excessive Bleeding (External or Internal)
• Assess severity whether to discontinue IV alteplase infusion
• Consider mechanical measures for external bleeding (eg compression of an
arterial or venous puncture site)
• If more than mild bleeding:
o Stop IV alteplase, Urgent FBC, PT/PTT/INR, fibrinogen, GXM 4 pints PC
o Prepare 6 units FFP, 10 units Cryoprecipitate, 6 units platelets.
o Consider cryoprecipitate and FFP
o Haematology consult

24. 24
15. Early Neurological Deterioration (END) Post Thrombolysis
• Post tPA re-occlusion may occur due to enhance platelet aggregation through
thrombin activation
• Influenced by BAD (40%), LAA (30%), Lacunar (5%).
• Mild stroke
o With LVO: proceed to EVT
o Non LVO or status unknown: Dual antiplatelet therapy (DAPT) or
anticoagulation/LMW heparin maybe beneficial after 24 hours post
thrombolysis
• Moderate stroke
o With LVO: proceed to EVT and post EVT may consider DAPT or LMW
heparin
o Non LVO: Consider DAPT or anticoagulation/LMW heparin
§ However, post thrombolysis early DAPT may increase END due to
bleeding
16. Post-thrombolysis and Post-thrombectomy Antithrombotic:
• Early Neurological Deterioration (END): 20-30%
• Early Recurrent Ischaemic Stroke (ERIS): AF: 8% vs Non-AF: 0.6%
• Late Recurrent Ischaemic Stroke (LRIS): Non-AF: 8-9%
• Early DAPT or Anticoagulation to reduce the rate of END, ERIS and LRIS
17. Cerebral Oedema
• Suspect raised ICP if:
o Drop in GCS
o Unequal pupils
o Nausea vomiting
o Hypertension with bradycardia
• Urgent CT brain
• Avoid excessive fluid administration
• Consider administration of 1g/kg of mannitol over 1 hour. If this is administered,
consider urinary catheter with Input output monitoring, and electrolyte balance.
• Neurosurgical consult
END
(1-7 days)
ERIS
(8-14 days)
LRIS
(15-90 days)