CURRICULUM VITAE

• Nama : Subandi, dr., Sp.S, FINS

• TTL : Tulungangung, 14 Agustus 1973
• Agama : Islam
• Instansi : RSUD Dr. Moewardi Surakarta
• Alamat : Griya pagotan B 11, Uteran, Geger Madiun
• Status Perkawinan : Menikah
– Nama Isteri : Etik Rakhmiyamti, dr, Sp.M
– Anak : 1. Annisa Salsabila R
2. M. Faiz Rahmadany
3. M. Fikrulihsan T
4. M. Rafif Rizqullah
 CURRICULUM VITAE
PENDIDIKAN
S1/ Dokter : FK Unibraw Lulus tahun 1998
Spesialis : FK Unair Lulus tahun 2009
Fellowship Intervensional Neurology and Stroke,
New-Delhi,2011- 2012

RIWAYAT PEKERJAAN
– RSI Blitar
– RSI Muhammadiyah Moga Pemalang
– Concord Pasific Pty Ltd Papua
– PTT Depkes RI
– PTT Daerah Kab. Madiun
– RSUD. Dr. Soetomo
– RSUD Dr. Moewardi
Intravenous and Intra-arterial
Thrombolysis
in Acute Ischemic Stroke

Subandi , dr . SpS. FINS

Division of Stroke & Neurointervention
Department Neurology Sebelas Maret University/ Moewardi Hospital
[email protected]

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 STROKE

MISTERI

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Infark meluas dengan bertambahnya waktu
Normal
Cerebral blood flow

Oligohaemic area Normal

Oligohaemic
Penumbra area
Penumbra

Ischaemic
Ischaemic core area

+ 1h. + 3h. + 12h. + 24h.

Time

• Adapted from:
• Donnan et al. Lancet Neurol 2009;8:261-269;
• Moustafa & Baron. Br J Pharmacol 2008;153:S44-S54;
22-Oct-16 sympo Sunshine 2016 • Saver. Stroke 2006;37:263-266.
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Management Stroke
• Supportif
• Neurorestorasi
• Neurorehabilitasi
• Neuroproteksi
• Revascularization  Recanalization – Reperfusi
• Anticoagulan-Antiagregasi

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• IV THROMBOLYSIS
• IA THROMBOLYSIS
• MECHANICAL THROMBECTOMY

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 Action for Reperfusion in
Ischemic Stroke

Step 1 Step 2 Step 3 Step 4 Step 5

secondary
< 4.5 hours <6 hours < 8 hours sub acute
Staff
prevention Patient
In-Service Outcomes

IV IA Thrombolysis Mechanical Intracranial Carotid /Vertebral

Thrombolysis Thrombectomy Stent Angioplasty & Stenting

Time is Brain
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(AHA/ASA, 2013) :
SPINAL

CEREBRAL
RETINA

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 STROKE: Major Health Problem
increased ~65% until 2025

Estimated number of strokes in USA during 2002-2025

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Broderick JP et al. Stroke 2004;35:205-211
Stroke types and incidence

Haemorrhagic
Other
12%
5%

Cryptogenic Atherosclerotic
30% cerebrovascular
disease
20%

Small vessel
Cardiac disease
embolism “lacunes”
20% 25%

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 Emergency Stroke Pathway

Pra RS
―Ambulance

IGD
― Triase
― Tim Code Stroke Radiologi
― Laboratory
― CT Scan Kepala Polos
― rTPA IGD
― rTPA Unit
Stroke

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Symptom of Stroke

“SEGERA RAWAT KE RUMAH SAKIT”

Se—Se nyum mencong

Ge—Ge rakan lengan dan tungkai lemah/lumpuh
Ra—sua Ra pelo
Ra—Rasa baal/mati rasa sesisi tubuh atau sekitar mulut
Wat –Melih(W)at ganda atau penglihatan hilang pada sebelah mata
Ke—Ke seimbangan terganggu/Ke sadaran menurun/tidak sadar
Rumah—muntah
Sakit—sakit kepala (Kemenkes, 2014)

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NINDS Study (1995) – Thrombolytic (t-PA) given IV within 3 hours of
stroke symptom onset for treatment for acute ischemic stroke:

• Approved in US in 1996

• Approval in Canada in 1999

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Preparing rTPA (30 -60 menit)

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IGD : Anamnesis

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Onset Time

• Onset Time = Time when patient was last seen well

• Requires detective skills

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 EMERGENCY ROOME: Early Evaluation
Airways, Breathing, Circulation (ABCs)
 iv line
 Head up 30°
 Cek saturasi O2 => berikan O2 jika diperlukan*

Gula Darah Sewaktu

 Hipoglikemia: <60 mg/dL => 30 mL glucose 20% to 40% iv
 Hiperglikemia: ≥200 mg/dL => bebas infuse glukosa

Tekanan Darah
 Hipertensi: SBP >220 mmHg; DBP >120 mmHg => Nicardipin atau Nitrat IV

*Caution in COPD patients • AHA. Time Lost is Brain Lost. 2011;

CHF, congestive heart failure • Fonarow et al. Stroke 2011;42:2983-2989; Adams et al. Stroke 2007;38:1655-1711.
DBP, diastolic blood pressure
• Kessler et al. Dtsch Arztebl Int 2011;108(36):585-591.
SBP, systolic blood pressure
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Clot Formation Cascades

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IV Thrombolysis: inclusion criteria

1. Ischemic Stroke
2. Patients of both sexes aged ≥ 18 years
3. Onset of symptoms within 4·5 hours (at administration of rt-PA)
Ischemic stroke
4. Patients (or family members) must have received treatment
information and have given consent to the use of their data and
to follow-up procedures

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Absolut exclusion criteria

1. Stroke onset>4·5 hours

2. Intracranial hemorrhage on brain CT, suspicion SAH
3. 4. Administration of i.v. heparin in the previous 48 h and aPTT above
laboratory normal upper limit
5. Platelet count <100 000/mm3
6. Neoplasm with increased hemorrhagic risk
7. Severe liver disease, including liver failure, cirrhosis, portal hypertension
(esophageal varices), active hepatitis
8. Hemorrhagic retinopathy (e.g. changes in vision in diabetics)
9. Ulcer disease of the gastrointestinal tract (< 3 months)

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 Relative exclusion

1. Unknown time of onset or stroke present on awakening

2. Seizure at stroke onset
3. Blood glucose<50 or>400 mg/dl
4. History of stroke in the last three-months
5. Clinically severe stroke (e.g. NIHSS>25) and/or severe according to appropriate
neuro-imaging techniques
6. Patient on anticoagulant treatment with low molecular weight heparins
7. Pregnancy
8. Major surgery or severe trauma <3 months

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ASPECTS Score

ASPECT score is:

• Alberta Stroke Program Early CT score (ASPECT) is
a 10-points quantitave topographic CT scan score

• ASPECT was developed to offer reliability and

utility of as standart CT examination with a
reproducible grading system to assess early
ischemic changes on pre-treatment CT in patient
with acute ischemic stroke of anterior circulation

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 Normal = 10
<7 = no recomemended for
thrombolysis

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MRI DIFFUSION-PERFUSSION

from : Majda Thurnher, 2008 Brain Ischemia -

Imaging in Acute Stroke Department of
Radiology, Medical University of Vienna

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 Male, 60 yo, was reffered to Moewardi hospital, e/c suddenly left
hemiplegi, consiouness , BP 180/100mmHg

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 IV Thrombolysis
Alteplase rTPA
0.9mg /Kg

10% of total dose –Bolus 2-3 mins

90% of total dose –Infuse over 60 mins

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Complication rTPA

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OBSRVATION POST THROMBOLYSIS
• BEDREST
• Neurological Observation
BP ~ 15 min for 2 hr
BP ~ 30 min for 6 hr
BP ~ 1-2 hr fo 16 hr
Limb power with MRC grading
NIHSS
HeadacheVomitus
Minor and Major bleeeding

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OBSERVATION POST THROMBOLYSIS
• BEDREST
• Neurological Observation
BP ~ 15 min for 2 hr
BP ~ 30 min for 6 hr
BP ~ 1-2 hr fo 16 hr
Limb power with MRC grading
NIHSS
Minor and Major bleeeding

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• Swallow assesment
• No !! : - Antiplatelet / heparin
- NGT
- arterial puncture/central line
• Avoid catheterization

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COMPLICATION
• EXTRA-CRANIAL HAEMORRAGHE
• INTRACEREBRAL HAEMORRAHGE
• ANAPHYLAXIS
• ELEVATED BLOOD PRESSURE

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Treatment ICH
• Stop alteplase infusion
• Airway, oxygenation, circulation
• Head 300 jugular venous drainage - ICP
• BP <160/90 over 6hrs
• Platelet infusion 6-8 units
• Cryoprecipitate 6-10 bags
• Tranexemic acid 1 gm iv
• FFP 15-20 ml/kg

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 IAT ??

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Intra-arterial fibrinolysis is beneficial for treatment of carefully
selected patients with major ischemic strokes of <6 hours’
duration caused by occlusions of the MCA who are not otherwise
candidates for intra-venous rtPA (Class I; Level of Evidence B).

The optimal dose of intra-arterial rtPA is not well established, and

rtPA does not have FDA approval for intra-arterial use.

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 Benefits of IA thrombolysis
• To directly access the occluded vessel
• Lower dose of rt-PA given  reduce the sistemic
side effect and intracranial bleeding
• Extending the time window up to 6 hour for
anterior circulation or 12-24 hour for posterior
circulation
• Recanalization rate is higher than IV thrombolysis
particularly with high load thrombus in large vessel
( ICA, basilar artery and M1 segment of MCA)
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 Weakness

• A complex procedure
• Require of technique
• Not always available anywhere
• Time consuming preparation
• Costly procedure

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 Evidence IAT ??

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PROACT II
- A prospective, phase III randomized trial n = 180
- Using r-pro-UK to treat MCA (M1 or M2) occlusions within 6 hours of
stroke symptom onset.
- Selection criteria included NIHSS score ≥4 (except isolated aphasia or
hemianopia) and age 18 to 85 years.
- Result : MCA recanalization was achieved in 66%
sICH occurred in 10% of patients treated with r-pro-UK and
in 2% of the control group

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Middle Cerebral Artery Embolism Local Fibrinolytic
Intervention Trial (MELT)
• MELT compared medical management with intra-arterial
urokinase within 6 hr
• Primary end point
- mRS score 0–2 were numerically higher in the urokinase-treated
group than the control group,
- recanalization 49.1% versus 36.8%; (P=0.35).
- sICH occurred in 9%.
- effect size and sICH rates were consistent with the results of
the PROACT II and meta-analysis (combined with PROACT II)

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 IV plus IA Thrombolysis
Shaltoni et al 2007
• n=69, age 60 NIHSS 18
• Patients with persisting occlusion a/o lack of clinical improvement
after iv thrombolysis
• IV rtPa started med 120 min, IAT med 288 min
• Reteplase n=56, alteplase n=7, urokinase n=6
• Symptomatic ICH n=4 ( 5.8%)
• Recanalisation in 50%
• Combination safe compared with iv alone. Higher rate of
recanalisation and favourable outcome

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• Ernst et al, Stroke 2000
- n : 20
- NIHSS : 11- 31 (med 21)
- Time IVT : 2-4 hr IAT : 3h 30min
- Recanalization : 69 %
- sICH : 9%
- mRS 0-2 : 10 of 16 pt

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 IAT window  door-to-puncture time‖!?
Door-to-drug time (IVT), plus‖:
– DSA-Lab preparation time
– Cathlab-Team activation time

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TECHNICAL PROCEDURE

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Case
• Patient with sudden decrease of consciousness.
He arrived in hospital ~6 hours after ictus. GCS
E2V2Mx. Diparesis, R>L with diminished right
corneal reflex. Basilar artery thrombosis dens
(white arrow)
• Basilar artery thrombosis is a true
neurointerventional emergency.
• Due to refferal issue to hospital with angio suite
facility
• He regained consciousness gradually and fully
recovered without any neurological deficits after
7 hours post treatment

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Before IAT After IAT

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 MECHANICAL THROMBECTOMY ??

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2013

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 2013
• IMS ( Interventional Management of Stroke –III)
• SYNTHESIS Expansion trial
• MR RESCUE Study

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2014
• MR CLEAN (Multicenter Randomized Clinical trial of Endovascular
treatment for Acute ischemic stroke in the Netherland)
• ESCAPE trial
• EXTEND IA TRIAL
• STAR STUDY

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 Case 1
• Male 26yo, with hemiplegia left side, slurred speech, numbness on left side
of body,
• CT head normal, CTA occlusion right MCA territory
• Risk factors : alcoholism, Smoker, Drugs abuse

Patient of dr. Bambang Tri Prasetyo, SpS, FINS. RS Pusat Otak Nasional, Jakarta
 Digital Substraction Angiography

Pre Mechanical thrombectomy Post Mechanical thrombectomy

Patient of dr. Bambang Tri Prasetyo, SpS, FINS. RS Pusat Otak Nasional, Jakarta
 Mechanical thrombectomy with stent-retriever:
solitaire FR

Patient of dr. Bambang Tri Prasetyo, SpS, FINS. RS Pusat Otak Nasional, Jakarta
 Thank You
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