1. Stroke Thrombolysis Training
Dr. Indira Natarajan Clinical Lead Acute Stroke and TIA Services

2. WHO DEFINITION
“ rapidly developing clinical signs (at times global) of disturbance of cerebral function, lasting more than 24 hours with no apparent cause other than that of vascular origin”
This definition includes signs and symptoms of suggestive of
- ischaemic stroke
- haemorrhages (intracerebral)

3. Diagnostic Dilemma “ Stroke Mimics ” or “ Stroke Syndrome ”
10% - 15% of patients referred with possible stroke have something else
Some uncertainty is inevitable

4. Stop and Think! Drowsy and Delirious Patient with headache
Drowsiness, confusion and headache

5. Drowsiness / Delirium SEIZURES METABOLIC / TOXIC SUBDURAL HAEMATOMA
UNCONCONSCIOUS

6. ROSIER Scale Facial weakness +1 Arm weakness +1 Leg weakness +1
Speech disturbance
Visual disturbance
Loss of Consciousness
Seizure episode

7. Diagnostic Dilemma 68 year old Sudden onset
Right facial arm and leg weakness with speech disturbance
Vascular Risk factors:
Hypertension
Diabetes
32 year old
Dubious onset
Right facial arm and leg weakness
Stuttering course
No vascular risk factors
? Seizure
? Other causes

8. Treatments effective within first hours to days
Aspirin
Thrombolysis
Acute Stroke Unit
Hemicraniectomy

9. Effective treatment for 1 patient to benefit
Numbers treated to benefit one patient
Propotion of patients eligible
Asprin
100 %
Stroke Unit 20
100%
Thrombolysis 10
10%
Hemicraniectomy 2 2%

10. Hyper-acute treatment of Stroke
Re-Canalisation 10

11. Modified Rankin Scale 1 2 3 4 5 No Mild Moderately Severe Moderate
Independent
Dependent 11

12. TIME IS BRAIN
2 million neurons are lost every minute that treatment is delayed.
Saver JL. Time is brain—quantified. Stroke 2006;37: 263–266. 12

13. rt-PA trials meta-analysis
rt-PA trials meta-analysis. Benefit declines with increasing time to treatment, but scope for benefit up to 6h (Lancet 2004; 363: 768–74)
Benefit
Upper and lower 95% confidence limits
Line of no effect
Harm
3 hours
6 hours 13 13

14. Benefit of r-tpa at 90 days
Time between event and treatment
Odds ratio in favour of favourable outcome (95% CI)
Estimated number needed to treat for favourable outcome
0-90 minutes
2.55 (1.44 to 4.52)
3.0
minutes
1.64 (1.12 to 2.40)
7.0
minutes
1.34 (1.06 to 1.68)
14.1
minutes
1.22 (0.92 to 1.61)
21.4

15. Acute Stroke Services... 1 hour 1 hour ESD 0 - 4.5 hours
999
A Patient's Journey.....
1 hour
1 hour
ESD
hours

16. Exclude Hypo-glycaemia
Check List
Confirm diagnosis
Exclude Hypo-glycaemia
Confirm Onset Time
NIHSS scale
Eligibility
Contra-indications
Consent

17. NIHSS Scale International Scale Validated to be used across the world
Mainly used to maintain consistency in all research studies
Also to assess progress

18. Stroke Severity - NIHSS

19. Eligibility Age 80 or below Previously fit and independent
Onset time known and less than hours
CT excludes haemorrhage

20. Exclusions Recent surgery, biopsies arterial cannaulation
Increased bleeding risk
Past history of intracranial haemorrhage
Any CNS pathology other than current stroke
Any past stroke plus diabetes
Stroke within 3 months
Systolic blood pressure >185
NIHSS < 4 or NIHSS > 25

21. Benefit of thrombolysis according to age group. Mishra. et
Benefit of thrombolysis according to age group Mishra. et.al BMJ 2010; 341:c6046

22. Other ways of saving the Penumbra if beyond 3 - 6 hours
Neuro-protection and
Re-perfusion 22

23. Saving the Penumbra…….. Anitplatelets Aspirin and Dipyridamole
Hydration use normal saline first 24 h
Temperature keep below 37.5
Oxygenation treat if saturation <92%
Blood glucose keep < 10 mmol/l
Nutrition maintain
Pain Control Analgesics
Blood pressure Target / in normotensives Target 180/ in hypertensives
European Stroke Initiative ( unchanged in 200 23

24. Getting the right patient to the right place......
Admitting patient to the Acute Stroke Unit within 4 hours

25. Management of Complications

26. Figure 1 European Cooperative Acute Stroke Study (ECASS) classification of intracerebral haemorrhage (ICH) following thrombolysis (from Berger and colleagues38). (A) HI-1; (B) HI-2; (C) PH-1; (D) PH-2
Derex, L et al. J Neurol Neurosurg Psychiatry 2008;79:
Copyright ©2008 BMJ Publishing Group Ltd. 26

27. Intracranial Haemorrhage Stop alteplase infusion
Immediate non contrast CT head
Immediate
PT, APTT, fibrinogen FBC/Group and save
Prepare
6 units platelets
Prepare
6 units cryoprecipitate
Haemorrhage on CT? NO
YES
Check lab results
Give cryoprecipitate and platelets
Notify Neurosurgeons
Resume alteplase infusion
Khaja, Lancet 2007; 396:

28. Intracranial haemorrhage within 36 h
7 % risk of Intracranial Haemorrhage
(2 %of which were fatal)
Asymptomatic 5%

29. Risk of haemorrhage depends on stroke severity
NIHSS> 20 => haemorrhage risk 17%
NIHSS <10 => Haemorrhage risk 3%
Stroke 1997;28(11):

30. Extracranial bleeding
Stop alteplase infusion
Immediate PT, APTT, fibrinogen, FBC, group and save
Use mechanical compression, if possible, to control bleeding form puncture sites
Support circulation with fluids and blood transfusion, as appropriate
For severe life threatening bleeding tranexamic acid 1 g i.v. over 15 min, repeated at 8 h if needed
Consider transfusion of FFP and/or cryoprecipitate depending on the results of the coagulation screen

31. Reperfusion cerebral oedema
Elevate the head to 30 degrees
Correct hyperthermia, hypoxia, hyperglycaemia, hypotension
Mannitol mg/kg over 20 min i.v., repeat q 6-8 h, if necessary
Dexamethasone 4 mg iv qds*
Frusemide mg iv*
Avoid antihypertensives, especially vasodilators
The goal of hyperosmolar therapy is to increase the serum osmolarity to approximately 315–320 mOsm/L Steiner Neurol 2001
Consider decompressive hemicraniectomy (once clotting correct/corrected)
If symptoms improve with mannitol reduce dose/frequency gradually
AHA/ASA Stroke 2007;38: *as used by C. Roffe in Stoke, not in AHA/ASA guidance 31

32. Orololingual Angiooedema
Stop alteplase infusion
Antihistamines (clorpheniramine 10 mg i.v.)
Hydrocortisone 200 mg i.v.
Observe vital for signs of progression, dyspnoea, anaphylactic shock
Usually starts early after the start of rx
Resolves within 72 h
Insula infarct=> contralateral tongue oedema Entgelter 2005
Most are on ACEI
1.9% after stroke thrombolysis 0.05% after MI thrombolysis
Other rx ranitidine
clemastin
If sx are mild and non-progressive, alteplase can be restarted under close observation
Khaja, Lancet 2007; 396: 32

33. Anaphylaxis Stop alteplase infusion
Urgent medical assessment: Airway, Breathing, Circulation
Adrenaline ml 1:1000 im or sc (not iv)
Clorpheniramine 10 mg i.v.
Hydrocortisone 200 mg i.v.
Salbutamol nebulizer 5 mg
If shocked i.v. saline and consider repeat doses of adrenaline

34. Thank you
Any Questions ?