1. Updates in the Treatment of Acute Stroke
Sarah Keir
Western General Hospital

2. Acute Stroke Update Stroke: the scale of the problem
Pathophysiology of stroke
Rationale for thrombolysis
Identification of stroke suitable for thrombolysis
Delivery of thrombolysis

3. Scale of the Problem UK 120,000 strokes annually
Scotland 10,000 strokes annually
Incidence 3/1,000
Prevalence 10/1,000

4. Mortality In The UK Stroke is the second commonest cause of death
Death within 30 days
8-12% ischaemic strokes
37-38% intracerebral haemorrhages
Death within a year of first stroke
22% men
25% women
Men
Women
IHD
20%
16%
Stroke
7.9%
12.9%
Lung cancer
6.9%
4.5%
Breast cancer

5. The Cost of Stroke Commonest cause of disability
50% survivors disabled at 6 months
Over 300,000 living with moderate to severe disability from stroke
28% strokes occur under 65 years of age
14% will have another stroke or tia within a year
Of 1 million people …
2000 have a new stroke
10,000 are living with stroke …

6. The Cost of Stroke 20% of all acute hospital beds 25% long-term beds
Cost of stroke to NHS £2.8 billion
3-4% of total healthcare costs in western Europe
Informal care cost £2.4 billion

7. Pathophysiology Of Acute Stroke

8. Time is Brain

9. Restore Cerebral Blood Flow: Dissolve the Clot (thrombolysis)
Before After

10. Any Problems with Trying to Remove Clot?…
…The brain is not the heart
It is much more fragile and more likely to bleed

11. NNT
91 – 180 9
180 –
(ns)
MI 30

12. Effectiveness of treating 2,000 new ischaemic stroke patients each year each year
Strategy Target Pop ARR Number of dead
or dependent
prevented
Aspirin 1,900 (95%) 1.2% 23
Thrombolysis 200 (10%) 5.9% 12
Stroke unit 1,600 (80%) 4.3% 69

13. To Summarise so far… Stroke is common Stroke is deadly and disabling
Thrombolysis works…
…but increases intracerebral haemorrhage which may lead to death
The time window is tiny

14. Identification of Suitable Stroke Patients
Get the patient into hospital quickly
Or else it’s pointless
Is it really a stroke?
Exclude stroke mimics
What part of the brain is affected?
Informs prognosis
How bad is it?
Helps assess risk of thrombolysis

15. FAST Stroke Assessment
Face Arm Speech Test
Facial Palsy
affected side
Arm Weakness
Speech Impairment
100% sensitivity / 92% specificity

16. Is it Really a Stroke? Stroke Mimics
Syncope
Seizure
Sepsis
Migraine
Metabolic
Tumour
Functional
Old Stroke
20 – 40% case series
Definition
“Rapidly developing clinical signs of focal (or global) disturbance of cerebral function, with symptoms lasting 24 hours or longer or leading to death, with no apparent cause other than vascular origin.” Hatano, WHO, 1976
ACCURATE HISTORY IS ESSENTIAL

17. What Part of the Brain is Involved?
* HCD – higher cortical dysfunction

18. How Bad is it? National Institute of Health Stroke scale
0 = no stroke
1-4 = minor stroke
5-15 = moderate stroke
15-20 = moderate/severe stroke
21-42 = severe stroke

21. Thrombolysis: Getting Ready to Give it
Does the patient fulfil licencing criteria?
Check for contraindications
Getting patient consent (relative assent)
What if they’re outside criteria/ have a contraindication?

22. Thrombolysis: Licence Criteria
Age 18 – 80
Within 3 hours of onset of symptoms
No haemorrhage on CT

23. Suitability For Thrombolysis
Contraindications (stroke-specific)
Unknown time of onset
Systolic BP >185 mmHg or diastolic BP >110mmHg or aggressive treatment needed to reduce BP to these limits
Blood glucose > 22.2 mmol/l OR < 2.8 mmol/l
Rapidly resolving symptoms
Minor stroke (NIHSS <5)
Severe stroke (NIHSS >25) or by imaging
Seizure at onset
Evidence of ICH on CT scan
Symptoms suggestive of SAH even if CT negative
Received heparin within 48 hrs & APTT > upper limit of normal
Any history of prior stroke and diabetes
Prior stroke within 3 months
PT > 15 sec (INR > 1.7)
Platelets below 100
Contraindications (general)
Known bleeding diathesis
Receiving warfarin
History of ICH
Suspected or previous aneurysmal SAH
History of CNS damage (tumour, aneurysm, intracranial or spinal surgery)
Haemorrhagic retinopathy
(<10 days) traumatic CPR, childbirth, puncture of non-compressible vessel
Severe hypertension
Bacterial endocarditis, pericarditis
Acute pancreatitis
Ulcerative gi disease <3/12, oesophageal varices, arterial aneurysms, a-v malformations
Severe liver disease, liver failure, cirrhosis, portal hypertension, active hepatitis
Major surgery or significant trauma (<3/12)

24. Suitability For Thrombolysis
Contraindications (stroke-specific)
Unknown time of onset
Systolic BP >185 mmHg or diastolic BP >110mmHg or aggressive treatment needed to reduce BP to these limits
Blood glucose > 22.2 mmol/l OR < 2.8 mmol/l
Rapidly resolving symptoms
Minor stroke (NIHSS <5)
Severe stroke (NIHSS >25) or by imaging
Seizure at onset
Evidence of ICH on CT scan
Symptoms suggestive of SAH even if CT –ve
Received heparin within 48 hrs & APTT > upper limit of normal
Any history of prior stroke and diabetes
Prior stroke within 3 months
PT< 15 sec (INR < 1.7)
Platelets below 100
Contraindications (general)
Known bleeding diathesis
Receiving warfarin
History of ICH
Suspected or previous aneurysmal SAH
History of CNS damage (tumour, aneurysm, intracranial or spinal surgery)
Haemorrhagic retinopathy
(<10 days) traumatic CPR, childbirth, puncture of non-compressible vessel
Severe hypertension
Bacterial endocarditis, pericarditis
Acute pancreatitis
Ulcerative gi disease <3/12, oesophageal varices, arterial aneurysms, a-v malformations
Severe liver disease, liver failure, cirrhosis, portal hypertension, active hepatitis
Major surgery or significant trauma (<3/12)

25. Suitability For Thrombolysis
Contraindications (stroke-specific)
Unknown time of onset
Systolic BP >185 mmHg or diastolic BP >110mmHg or aggressive treatment needed to reduce BP to these limits
Blood glucose > 22.2 mmol/l OR < 2.8 mmol/l
Rapidly resolving symptoms
Minor stroke (NIHSS <5)
Severe stroke (NIHSS >25) or by imaging
Seizure at onset
Evidence of ICH on CT scan
Symptoms suggestive of SAH even if CT –ve
Received heparin within 48 hrs & aptt > upper limit of normal
Any history of prior stroke and diabetes
Prior stroke within 3 months
Pt < 15 sec (inr < 1.7)
Platelets below 100
Contraindications (general)
Known bleeding diathesis
Receiving warfarin
History of ICH
Suspected or previous aneurysmal SAH
History of CNS damage (tumour, aneurysm, intracranial or spinal surgery)
Haemorrhagic retinopathy
(<10 days) traumatic CPR, childbirth, puncture of non-compressible vessel
Severe hypertension
Bacterial endocarditis, pericarditis
Acute pancreatitis
Ulcerative gi disease <3/12, oesophageal varices, arterial aneurysms, a-v malformations
Severe liver disease, liver failure, cirrhosis, portal hypertension, active hepatitis
Major surgery or significant trauma (<3/12)

26. Suitability For Thrombolysis
Contraindications (stroke-specific)
Unknown time of onset
Systolic BP >185 mmHg or diastolic BP >110mmHg or aggressive treatment needed to reduce BP to these limits
Blood glucose > 22.2 mmol/l OR < 2.8 mmol/l
Rapidly resolving symptoms
Minor stroke (NIHSS <5)
Severe stroke (NIHSS >25) or by imaging
Seizure at onset
Evidence of ICH on CT scan
Symptoms suggestive of SAH even if ct –ve
Received heparin within 48 hrs & APTT > upper limit of normal
Any history of prior stroke and diabetes
Prior stroke within 3 months
PT < 15 sec (INR < 1.7)
Platelets below 100
Contraindications (general)
Known bleeding diathesis
Receiving warfarin
History of ICH
Suspected or previous aneurysmal SAH
History of CNS damage (tumour, aneurysm, intracranial or spinal surgery)
Haemorrhagic retinopathy
(<10 days) traumatic CPR, childbirth, puncture of non-compressible vessel
Severe hypertension
Bacterial endocarditis, pericarditis
Acute pancreatitis
Ulcerative gi disease <3/12, oesophageal varices, arterial aneurysms, a-v malformations
Severe liver disease, liver failure, cirrhosis, portal hypertension, active hepatitis
Major surgery or significant trauma (<3/12)

27. Suitability For Thrombolysis
Contraindications (stroke-specific)
Unknown time of onset
Systolic BP >185 mmHg or diastolic BP >110mmHg or aggressive treatment needed to reduce BP to these limits
Blood glucose > 22.2 mmol/l OR < 2.8 mmol/l
Rapidly resolving symptoms
Minor stroke (NIHSS <5)
Severe stroke (NIHSS >25) or by imaging
Seizure at onset
Evidence of ICH on CT scan
Symptoms suggestive of SAH even if CT –ve
Received heparin within 48 hrs & APTT > upper limit of normal
Any history of prior stroke and diabetes
Prior stroke within 3 months
PT < 15 sec (INR < 1.7)
Platelets below 100
Contraindications (general)
Known bleeding diathesis
Receiving warfarin
History of ICH
Suspected or previous aneurysmal SAH
History of CNS damage (tumour, aneurysm, intracranial or spinal surgery)
Haemorrhagic retinopathy
(<10 days) traumatic CPR, childbirth, puncture of non-compressible vessel
Severe hypertension
Bacterial endocarditis, pericarditis
Acute pancreatitis
Ulcerative gi disease <3/12, oesophageal varices, arterial aneurysms, a-v malformations
Severe liver disease, liver failure, cirrhosis, portal hypertension, active hepatitis
Major surgery or significant trauma (<3/12)

28. IV tPA - Patient Information
Outcome at 90 days:
Usual Treatment Clot-Busting Treatment
(Aspirin & supportive care) (Thrombolysis)
1 in 10 greater chance of independence (being able to carry out all previous activities or with only a slight disability)
1 in 10 reduced risk of being dependent (requiring help to walk or needing help with most bodily needs)
1 in 30 chance of symptomatic haemorrhage (commonly leading to death)

29. What if they’re ‘Not Suitable’?
Just give it any way
Cleveland
SICH 15.7%
Just out of time?
ECASS 3
Up to 4.5 hours
mean NIHSS 9
(smaller) benefit
Cleveland treated 50% outside guidelines

30. Randomise into IST3 No upper age limit No BP criteria
Clinical equipoise
Recruiting to 2011, reporting 2012
Aiming 3100
Currently 2800 – on target

31. Other Ways to Reperfuse
Intra-arterial thrombolysis
Clot retrieval
…jury is still out…

32. Delivering Thrombolysis: Drug Delivery
Must be initiated by a physician specialised in neurological care
Dose is different to that for myocardial infarction
0.9 mg / kg (Max. 90mg)
10% as initial IV bolus
Infuse rest over 60 mins.
Avoid Aspirin & Heparin for 24 hours

33. Monitoring Cardiac monitor Oxygen saturation Monitor BP & GCS
15 mins during infusion
30 mins for next 6 hours
Hourly for 6 hours
4 hourly for 36 hours
NIHSS at 2 hours
Avoid NG tube, catheter, central lines, arterial puncture for 24 hrs

34. Physiological Stabilisation
IV saline
Avoid hypotonic solutions
Keep temperature below 37 oC
Paracetamol, cooling
Maintain O2 saturation > 95%
Avoid hyperglycaemia
Worsens outcome
Watch BP closely
Increased risk at extremes
Use short-acting drugs if necessary

35. Complications Symptomatic haemorrhage ~ 7.3% If bleeding:
Reduced GCS, headache, nausea, vomiting, hypertension, worsening symptoms
If bleeding:
Urgent FBC, fibrinogen, INR, APTT
Platelet infusion 6-8 units
Cryoprecipitate 6-8 units (or FFP)
Factor VIII
Discuss with neurosurgery (SAH or subdural)
Mortality
11.3% SITS-MOST
17.1% in trials
30% natural history of stroke
Essential to adhere to protocols

36. Complications Angio-oedema and anaphylaxis Stop infusion of rt-PA
Urgent medical assessment – ‘ABC’
Hydrocortisone 200mg IV
Chlorpheniramine 10mg IV
Salbutamol nebuliser – 5mg
if severe reaction:
Adrenaline 0.5-1ml of 1 in1000 IM
Fluid resuscitation if shocked and consider repeat doses of adrenaline as required

37. Requirements for Delivering Thrombolysis
Place to deliver it
Acute stroke unit
CCU
HDU
Fast access to neuroimaging
Within hours
Out of hours
Patients
Front door staff
Nurses, doctors
Radiographers
Radiologists
Minimum door-to- needle time at WGH is 30 minutes

38. Delivering Thrombolysis Regionally:Telemedicine

39. Thrombolysis: the Challenges
Getting the patients to attend quickly
Getting hospital staff to attend the patient quickly
Get the neuroimaging quickly
Getting enough staff for a 24/7 service
Getting enough staff with expertise in every hospital
Making it as safe as possible – tailoring treatment to the patient