Management of stroke acute: a

review of current evidence

Dr Julie Considine

Senior Research Fellow

Deakin University-Northern Health Clinical Partnership, Victoria, Australia

Definitions

Stroke

> acute neurological injury that is caused by interruption to

blood flow to an area of the brain

> classified according to cause

• ischaemic stroke (80%)

• haemorrhagic stroke (20%)

TIA

> brief episode of neurologic dysfunction caused by focal

brain or retinal ischemia, with clinical symptoms typically

lasting less than one hour, and without evidence of acute

infarction

> move away from old definition

• neurological deficit caused by focal brain ischemia that completely

resolves within 24 hours

Causes

Ischaemic stroke

> thrombotic stroke

> embolic stroke

> hypoperfusion

Haemorrhagic stroke

> most common cause: hypertension

Pathophysiology

Ischaemic stroke

> cerebral injury is directly related to decreased blood

supply

> cells die centre of the affected area

> affected area is surrounded by an area where injury to

the cells is potentially reversible (penbumra)

Haemorrhagic stroke

> cerebral injury occurs as a result of

• increased intracranial pressure

• local compression

• decreased perfusion

Risk management

Risk stratification for stroke

> progression of TIA to stroke significant mortality &

morbidity

> risk of stroke after TIA

• 4% to 8% in the first month

• 12% to 13% in the first year

Aplin 2004

Patient related risk factors for stroke

> non-modifiable

• age / male gender / positive family Hx

> modifiable

• hypertension / risk factors for atherosclerosis

• cardiac risk factors / carotid stenosis or carotid bruit (blockage) in

asymptomatic patients

Risk management

Risk stratification for stroke following TIA> ABCD2 tool - highly predictive for stroke after TIA

score from maximum 6 pts 0-3 points: low risk

4-5 points: moderate risk

6-7 points: high risk

Rothwell, et al. 2005; Johnson et al 2007

Age 60 yrs = 1 pt

Blood pressure SBP>140 mmHg and/or DBP90

mmHg = 1 pt

Clinical Hx unilateral weakness = 2 pts

speech involvement without

weakness = 1 pt

Duration > 60 mins = 2 pts

10-59 mins = 1 pt

Diabetes Hx diabetes = 1 pt

Signs & symptoms

Signs and symptoms of stroke

> are variable

> depend on the area of the brain affected

> clinical differentiation between ischaemic &

hemorrhagic stroke is unreliable

> haemorrhagic stroke more commonly associated with

• history of prolonged hypertension

• sudden onset of symptoms - headache / vomiting / collapse

• history of anticoagulant medications

Signs & symptoms

Initial assessment

Stroke

> is a medical emergency

> accurate assessment of onset of symptoms is

important

> early recognition, diagnosis, treatment & referral to

specialist services

• improves patient outcomes

• prevents complications

Triage

> actual or potential stoke is a time critical presentation

> use ‘FAST’ criteria and patients with high risk features

of TIA (ABCD2) to inform triage decisions

Airway / Breathing

> ensure patent airway

• position

• use of airway adjuncts - oropharygeal / nasopharyngeal

• intubation if decreased conscious state

> assess respiratory status

• respiratory rate, respiratory effort, SpO2,

> prevent / treat hypoxia

• hypoxia increases cerebral injury

• ensure adequate ventilation & oxygenation

> stroke patients have lower oxygen levels (SpO2 ) than

controls

• upright position

• supplemental oxygen if SpO2<95%

• oxygen controversial in non-hypoxic patients

Circulation> assess circulation

• heart rate, blood pressure, cardiac rhythm

> aim to optimise cerebral perfusion

• minimise infarct size / cerebral injury

> hypotension

• is uncommon in stroke

• should be treated aggressively as it compromises cerebral

perfusion

> hypertension

• common physiological response to preserve cerebral perfusion

pressure

• aggressive blood pressure reduction is NOT recommended

• use of oral or sublingual agents is NOT recommended

• exclude or treat other causes for hypertension : pain, vomiting or

urinary retention

Circulation

> ECG abnormalities are common

• 60% of patients with cerebral infarction

• 50% of patients with intracerebral haemorrhage

• 75% of patients with acute stroke have T wave inversion

> cardiac arrhythmias can occur from

• increased sympathetic tone

• decreased parasympathetic tone

• catecholamine release

> should be performed to identify

• sources of cardiogenic emboli - atrial fibrillation or recent AMI

(heart attack)

• signs of pre-existing cardiac disease

Disability (neurological status)

> assess conscious state

• Glasgow Coma Score

> optimise intracranial pressure

• ICP rises quickly after haemorrhagic stroke

• can take up to 48hrs to manifest in ischaemic stroke

• it is unclear if aggressive Mx of increased ICP improves

outcome in stroke

• early reduction in conscious state is poor prognostic indicator

Blood glucose

> monitor blood glucose level

> exclude hypoglycaemia as cause for symptoms

> exclude / identify hyperglycaemia • 20-50% of stroke patients are hyperglycaemic in ED

• 8-20% of stroke patients have diabetes

• due to known or unknown diabetes / stress response

> hyperglycaemia is associated with increased cerebral

injury and poor outcomes

> Weir et al. (1997) • examined effect of BSL on stroke outcomes

• BLS > 8 mmol/L was independent predictor of poor outcome

> elevated BSL should be actively corrected

Temperature

> sources of fever / hyperthermia following stroke

• infection preceding stroke - pneumonia / UTI /

• thromboembolism

> fever increases infarct size & mortality

> meta-analysis: Hajat et al, 2000

• 3790 patients in 9 studies

• 19% increase in mortality in febrile stroke patients

> mechanisms of cerebral injury related to pyrexia

• neurotransmitters associated with poor cerebral outcomes -

glutamate, g-aminobutyric acid, glycine

• free radical production

• blood-brain barrier is temperature-sensitive so increased protein

transfer across the blood-brain barrier during hyperthermia

• hyperthermia also increases cerebral metabolism

Swallowing assessment

> nil orally until swallowing is assessed

• impaired swallowing is associated with increased mortality

> early swallowing assessment is important

• prevent aspiration

• guide decisions about oral intake

• reduce the need for IV fluid or nasogastric tube feeds

> swallowing assessment should be performed by

trained personnel

• ideally speech pathologists

• dysphagia screening tools available

• assessment of gag is unreliable indicator of swallowing

Imaging> non-contrast CT

• most common investigation for completed stroke

• current guidelines recommend CT performed within 24 hours of

symptom onset

• usually occurs sooner, particularly if thrombolysis is treatment

option

• performed to exclude intracerebral haemorrhage prior to

anticoagulation or thrombolytic therapy

• many will be normal in the first few hours following ischaemic

stroke

> MRI

• superior to CT: identify early signs of infarction

• inferior to CT: identify haemorrhagic causes of stroke

Drug therapy for ischaemic stroke

Aspirin

> administration < 48 hours of onset of symptoms

• reduces early death & recurrent stroke

• if patient is unable to swallow, Aspirin should be administered

via an alternative route - NGT

• intracerebral haemorrhage should be excluded by CT scan prior

to Aspirin

Drug therapy for ischaemic stroke

Anticoagulation

> no evidence that anticoagulation decreases

• morbidity or mortality

• early recurrent stroke

> routine use of low molecular weight heparin is not

recommended for Mx of ischaemic stroke

• anticoagulation benefit for patients with atrial fibrillation &

stroke secondary to cardiogenic emboli

• best time to commence anticoagulation in these patients is

unknown

> prior to anticoagulation

• exclude intracerebral haemorrhage by CT scan

• obtain neurological consultation

• should occur prior to commencement of heparin

Drug therapy for ischaemic stroke

Thrombolysis> use in stroke still controversial in some circles but

routine in others

> current evidence • until recently - no support for use of thrombolysis in acute

ischaemic stroke beyond 3 hours of symptoms

• in 2008, two studies showed safe use of thrombolysis in acute

ischaemic stroke up to 4.5 hours of symptoms

• further research & advances in neuro-imaging may change the

criteria in future

Drug therapy for ischaemic stroke

Thrombolysis - NINDS (1995)

Drug therapy for ischaemic stroke

Thrombolysis - NINDS(1995)

> randomized, double-blind trial of t-PA for ischemic

stroke within 3 hrs (Part 1: n = 291 / Part 2: n = 333)

> results

• neurologic improvement at 24 hours: no difference

• patients treated with t-PA were at least 30% more likely to have

minimal or no disability at 3 mths

• symptomatic ICH rates within 36 hours : higher with

thrombolysis

6.4% vs 0.6%, p <0.001

• mortality @ 3mths : no difference

17% vs 21%, p = 0.30

Drug therapy for ischaemic stroke

Thrombolysis - NINDS reanalysis (Ingall, 2004)

> concerns about results from NIDS study

> data re-analysed by independent group

> results

• there were subgroup differences in baseline stroke severity but

the differences did not affect results

• symptomatic ICH rates: higher with thrombolysis

6.4% vs 0.6% (same as original study)

• favorable outcomes: higher with thrombolysis

OR = 2.1, 95% CI, 1.5 to 2.9

> conclusion

• use of t-PA for acute ischemic stroke < 3 hours of onset was

supported

Drug therapy for ischaemic stroke

Thrombolysis - Hacke et al. / Wahlgren et al. (2008)

Drug therapy for ischaemic stroke

Thrombolysis - Hacke et al. (2008)European Cooperative Acute Stroke Study (ECASS) group

> compared patients with acute ischaemic stroke treated

with alteplase 3h to 4·5h after symptoms versus

placebo (n = 821)

> results

• favourable outcome* @ 3 mths was higher with thrombolysis

52.4% vs. 45.2%, p = 0.04

• ICH rates: higher with thrombolysis

- any ICH: 27.0% vs. 17.6%, p = 0.001;

- symptomatic ICH: 2.4% vs. 0.2%, p = 0.008

• mortality: no difference

7.7% vs. 8.4%, p = 0.68

* modified Rankin score 0 or 1

Drug therapy for ischaemic stroke

Thrombolysis - Wahlgren et al. (2008)Safe Implementation of Treatments in Stroke (SITS) group

> compared patients with acute ischaemic stroke treated

with alteplase (n = 664)

• between 3h and 4·5h versus

• patients treated within 3h

> results - no differences in

• symptomatic ICH within 24 hrs

2·2% (14/649) versus 1·6% (183/11681) p = 0.24

• mortality

12·7% (70/551) versus 12·2% (1263/10 368), p = 0.72

• independence* @ 3 mths:

58·0% (314/541) versus 56·3% (5756/10231), p = 0.18

*modified Rankin scale of 0–2

Drug therapy for ischaemic stroke

Thrombolysis - current recommendations

(National Stroke Foundation Guidelines, 2007)

Drug therapy for ischaemic stroke

Thrombolysis - current recommendations

(National Stroke Foundation Guidelines, 2007)

Drug therapy for ischaemic stroke

Thrombolysis - ongoing issues> frequency of thrombolysis in acute stroke is low

> patient selection is important

• not all patients who present within 3 hrs (or 4.5hrs) will be

candidates for thrombolysis

• requires complex clinical decisions for some patients

• can be difficult to diagnose acute ischaemic stroke & exclude

subtle intracerebral haemorrhage

> local resource considerations

• imaging capabilities

• staff skills and knowledge - interpretation of images, general

care of acute stroke, specifics of thrombolysis administration,

management of complications if they occur

• infrastructure for care post thrombolysis

Mx of haemorrhagic stroke

Management

> depends on

• location / cause

• neurological deficit / patient’s clinical condition

> should include

• early neurosurgical referral for patients with potential for

surgical intervention

• Mx increased ICP

> cerebral oedema & increased ICP tend to occur more

acutely in haemorrhagic strokes

> ischaemic strokes can also have haemorrhagic

complications

Ongoing care

Stroke units

> better outcomes following stroke

> Indredavik et al (1999)

• assessed which aspects of stroke unit care resulted in better

outcomes

• 206 patients (stroke unit: n = 102, general wards: n = 104)

• analyzed measurable factors and their association discharge to

home within 6 weeks

> treatment factors that were different in stroke units

• increased use of oxygen, heparin, IV N/Saline & antipyretics

• decreased variation BP, hypotension

• hyperglycaemia / pyrexia

• all factors except glucose level were associated with discharge

to home within 6 weeks

Summary

> stroke is a medical emergency & time critical

presentation

> general management principles

• A - protect airway, prevent aspiration

• B - optimise oxygenation

• C - optimise blood pressure & cerebral perfusion, ECG

• D - optimise ICP and cerebral perfusion

• Other - blood glucose, temperature, swallowing

> Tx ischaemic stroke

• thrombolysis in specific patients

• anticoagulation in specific patients

• Aspirin

> Tx haemorrhagic stroke

• Mx increased ICP / surgical intervention