Acute Ischaemic Stroke
6/12/10
PY Mindmaps
Life in the Fast Lane
- with infarction there is an ‘ischaemic pendumbra’ and if adequate blood flow can be restored with in a critical time frame function may return to normal.
- generally classified into: (1) large vessel thrombotic, (2) small vessel thrombotic and (3) embolic
GENERAL ASSESSMENT AND MANAGEMENT
Resuscitation
- airway protection required in obtunded
- prevention of aspiration and hypoxaemia
- correct hypotension (patients are often hypertensive and this should not be treated to optimise perfusion to the pendumbra)
- treat seizures with anticonvulsants
- treat hypoglycaemia and control glucose to reasonable levels
- if thrombolysis considered control BP to less than 185/110 (agents: beta-blockers, calcium channel blockers, ACE-I, GTN)
- maintain normothermia (avoid fever)
Investigations
CT
- if rapid intervention required -> requires rapid CT
- ideally within 1 hour if any other following:
(1) indications for lysis or early anti-coagulation
(2) on warfarin
(3) known bleeding tendency
(4) depressed GCS (<13)
(5) unexplained progressive or fluctuating symptoms
(6) suspected meningitis
(7) severe headache
- excludes haemorrhage
- can demonstrate subtle hypodensity, loss of insular ribbon and hyperacute artery signs
- angiogram: can elucidate burden and distribution of thrombus) -> role is not clear
- xenon CT: can determine cerebral perfusion and identify the size of the ischaemic penumbra -> role un clear
MRI
- difficult to perform on emergent basis
- problems with identification of hyperacute haemorrhage
- DWI can show early ischaemia
- perfusion scan may identify reversible ischaemia
Therapies
Anti-coagulation
- role unclear
- no real change in recurrence
- increased risk of haemorrhage (1-3%)
Anti-platelet Therapy
- aspirin 300mg PO/NG/PR early (even OK prior to CT, Chen (2000), Stroke)
- addition of dipyridamole 200mg PO BD for TIA’s
- clopidogrel (only for those with aspirin allergy or associated ACS)
Thrombolytics
t-PA
- ECASS trial (European Cooperative Acute Stroke Study): RCT, tPA within 6 hours, patients with severe hemispheric strokes were excluded -> no difference in outcome and increased risk of bleeding
- ECASS II: strict exclusion of those with > 1/3rd MCA infarct on CT -> failed to demonstrate benefit (numbers needed to harm = 18)
- NINDS: tPA within < 3 hours, NNT to have minimal or no disability = 8, NNH to cause a ICH = 14, no difference in mortality.
- Canadian Altepase for Stroke Effectiveness study: co-hort study, n = 1135, similar benefit to NINDS with a lower ICH rate (4.6%)
Meta-analysis of the above: n = 2639, 37% achieved a favourable outcome, ICH rate 5.2%
- ALTANTIS A: patients enrolled within 6 hours, stopped early because of increased risk of haemorrhage and no favourable outcome.
- ALTANTIS B: aimed to assess efficacy within 5 hours -> no significant benefit, a sub-group treated within 3 hours had a trend towards benefit.
Meta-analysis of the above: n = 5216, significant improvement in outcome @ 3 months and increased risk of ICH.
Cochrane (2008) Review: n = 7152, all thrombolytics included -> significant reduction in death and dependency @ 3-6 months, but increase in deaths in first 7-10 days from ICH.
Sub-groups
- older patients tend to have more ICH’s
- ? possible association with hypodensities on early CT and haemorrhagic transformation
- ? unsure whether aspirin increases risk of ICH
- ? severity of stroke -> despite poorer outcomes and increased risk of haemorrhage more patients have good outcomes who are thrombolysed
SUMMARY
Indications
- consider within 3 hours of onset
- devastating neurological sequelae
- > 18 but < 80 years
- must have BP < 185/110
- ideally no changes on CT (hypodensity involving > 1/3 of MCA, oedema, mass effect -> increased risk of haemorrhage)
Contraindications
- haemorrhage on CT
- rapidly improvement in neurological symptoms
- only have minor symptoms (ataxia, minor sensory loss, dysarthria)
- previous ICH/SAH/neoplasm
- seizure at stroke onset
- recent surgery/trauma
- bleeding
- on heparin/warfarin
Dose
- 0.9mg/kg IV not exceeding 90mg (10% given as a push -> rest given over 60 min)
Streptokinase
- 3 large RCT’s against placebo (Europe MAST-E, Australian Streptokinase Trial, Italian MAST-I)
- all demonstrate an increase in haemorrhage with NNH to cause death or disability = 5
Intra-arterial Thrombolysis
- PROACT II Trial: RCT, saline vs urokinase -> improved functional outcomes @ 90 days but haemorrhage rate of 10% in treatment vs 2% of controls.
Combination Therapy
- IV thrombolysis + then intra-arterial tPA -> greater recanalisation but increased risk of bleeding, not powered to look at functional outcome.
Surgery
- decompressive craniectomy for malignant MCA infarction
- inclusion criteria:
(1) age 18-60 years
(2) decreased LOC
(3) within 48 hours
(4) CT signs involving atleast 50% of MCA territory
-> decreased mortality (mortality without intervention = 80%)
-> decreased disability significantly at 1 year
-> high proportion still dependent though
Other Neuroprotective measures
- many tried in animal models and none have shown benefit.
- there may be additive effects with some agents
- hypothermia is yet to be trialled
SUMMARY OF MANAGEMENT
- rapid resuscitation and assessment including non-contrast CTH
- thrombolysis: TPA if: within 3 hours, major neurological deficit, > 18 and < 80 years, BP < 180 systolic or < 110 diastolic, no obvious infarct or haemorrhage on CT, and no contraindications + neurologist opinion.
- surgical decompression: 18-60 years, at least 50% MCA territory and other territory involvement, within 48 hours
- secondary brain protection: hypoxia, hypotension, seizure prophylaxis, normothermia
OUTCOME ASSESSMENT
- Modified Rankin Scale
- assess degree of disability/dependence in daily activity post stroke
0 = no symptoms
1 = no significant disability (able to carry out usual activities despite some symptoms)
2 = slight disability (unable to carry out all previous activities)
3 = moderate disability (requires some help, able to walk unassisted)
4 = moderately severe disability (help with ADLs, assistance with walking)
5 = severe disability (constant nursing, bidden ridden, incontinent)
6 = dead
Jeremy Fernando (2010)