Management of acute ischaemic stroke: new guidelines from the American Stroke Association and European Stroke Initiative The Lancet Neurology Volume 2 • Number 11 • November 2003

Background 0·2% of the population each year Important cause of death and Dependency 1/6 patients die in the first month

0·2% of the population each year

Important cause of death and Dependency

1/6 patients die in the first month

Background 1/2 survivors are permanently disabled Despite best efforts to rehabilitate them and To prevent complications, recurrent stroke, And other serious vascular events Early, and ongoing, management : Reduction of both case fatality and Long-term disability

1/2 survivors are permanently disabled Despite best efforts to rehabilitate them and To prevent complications, recurrent stroke, And other serious vascular events

Early, and ongoing, management : Reduction of both case fatality and Long-term disability

Recent developments Guidelines Stroke Council of the American Stroke Association (ASA; Adams and co-Workers, Stroke 2003; 34: 1056–83) European Stroke Initiative (EUSI; European Stroke Initiative Executive Committee and Writing Committee, Cerebrovasc Dis 2003; 16: 311–38)

Stroke Council of the American Stroke Association (ASA; Adams and co-Workers, Stroke 2003; 34: 1056–83)

European Stroke Initiative (EUSI; European Stroke Initiative Executive Committee and Writing Committee, Cerebrovasc Dis 2003; 16: 311–38)

Recent developments Guidelines Remarkably similar, even regarding Controversial issues Evidence-based medicine and a major Step

Remarkably similar, even regarding Controversial issues

Evidence-based medicine and a major Step

Recent developments Guidelines ASA : Early diagnosis and management Of patients in the first 24–48 h of Ischaemic stroke EUSI :Primary and secondary stroke Prevention, rehabilitation, Improvement of public awareness of The symptoms of stroke, and the need For urgent medical attention after a Stroke

ASA : Early diagnosis and management

Of patients in the first 24–48 h of

Ischaemic stroke

EUSI :Primary and secondary stroke

Prevention, rehabilitation,

Improvement of public awareness of

The symptoms of stroke, and the need

For urgent medical attention after a

Stroke

Diagnosis Clinical history and examination CT brain scan: most important to Exclude non-vascular, structural, Intracranial lesions , brain ischaemia And haemorrhage

Clinical history and examination

CT brain scan: most important to Exclude non-vascular, structural, Intracranial lesions , brain ischaemia And haemorrhage

Diagnosis MRI :Contraindicated in metal implants, Cardiac pacemakers, or Claustrophobia ; and less widely Available, more costly, And less Reliable in identifying acute ICH MRI :Sensitive in the detection of brain Infarction

MRI :Contraindicated in metal implants,

Cardiac pacemakers, or

Claustrophobia ; and less widely

Available, more costly, And less

Reliable in identifying acute ICH

MRI :Sensitive in the detection of brain

Infarction

Diagnosis Further research : Diffusion and Perfusion MRI, magnetic resonance Spectroscopy, may be of additional help For the assessment of the risk to Benefit ratio for early reperfusion Therapy Vascular imaging (ultrasound, CT Angiography, and magnetic resonance Angiography)

Further research : Diffusion and Perfusion MRI, magnetic resonance Spectroscopy, may be of additional help For the assessment of the risk to Benefit ratio for early reperfusion Therapy

Vascular imaging (ultrasound, CT Angiography, and magnetic resonance Angiography)

Stroke-care delivery : Site Stroke unit rather than a general Medical ward (level I) Reduces the odds of death or Dependency : 22% (95% CI 11–32) Monitoring in an intensive care setting Is not necessary

Stroke unit rather than a general Medical ward (level I)

Reduces the odds of death or Dependency : 22% (95% CI 11–32)

Monitoring in an intensive care setting Is not necessary

Stroke-care delivery : Process Specialised, organised, and Multidisciplinary(medical, nursing, Physiotherapy, occupational therapy, Speech therapy, and social work staff)

Specialised, organised, and Multidisciplinary(medical, nursing, Physiotherapy, occupational therapy, Speech therapy, and social work staff)

General supportive care to maintain physiological homoeostasis Despite the absence of reliable evidence For the effectiveness of interventions Aimed at the maintenance of Physiological homoeostasis Airway support and ventilatory Assistance:reduced consciousness or a Compromised airway

Despite the absence of reliable evidence For the effectiveness of interventions Aimed at the maintenance of Physiological homoeostasis

Airway support and ventilatory Assistance:reduced consciousness or a Compromised airway

General supportive care to maintain physiological homoeostasis Target O 2 saturation: EUSI ≥92%; ASA ≥95% Antipyretic agents : if the body Temperature is high (high temperature Defined as: EUSI ≥37·5°C; ASA no Temperature threshold stated) Gradual lowering of high glucose concentrations : (target glucose : EUSI about 10 mmol/L; ASA <16·63 mmol/L) with normal Saline and insulin titration

Target O 2 saturation: EUSI ≥92%; ASA ≥95%

Antipyretic agents : if the body Temperature is high (high temperature Defined as: EUSI ≥37·5°C; ASA no Temperature threshold stated)

Gradual lowering of high glucose concentrations : (target glucose : EUSI about 10 mmol/L; ASA <16·63 mmol/L) with normal Saline and insulin titration

General supportive care to maintain physiological homoeostasis Low blood glucose :rapidly corrected With intravenous dextrose bolus or Infusion of 10–20% glucose Hypotonic solutions (NaCl 0·45% or Glucose 5%) should be avoided

Low blood glucose :rapidly corrected With intravenous dextrose bolus or Infusion of 10–20% glucose

Hypotonic solutions (NaCl 0·45% or Glucose 5%) should be avoided

General supportive care to maintain physiological homoeostasis Management of high BP is Highly controversial Lowering of BP unless : >200–220 mm Hg systolic or >120 mm Hg diastolic in Ischaemic stroke ; >180/105 mm Hg in a patient with haemorrhagic stroke Labetalol and sodium nitroprusside Avoidance of drugs such as sublingual Nfedipine

Management of high BP is Highly controversial

Lowering of BP unless : >200–220 mm Hg systolic or >120 mm Hg diastolic in Ischaemic stroke ; >180/105 mm Hg in a patient with haemorrhagic stroke

Labetalol and sodium nitroprusside

Avoidance of drugs such as sublingual Nfedipine

General supportive care to maintain physiological homoeostasis ASA : nicardipine ASA : 10–15% reduction EUSI : intravenous urapidil, Nitroglycerin, and oral captopril

ASA : nicardipine

ASA : 10–15% reduction

EUSI : intravenous urapidil, Nitroglycerin, and oral captopril

General supportive care to maintain physiological homoeostasis EUSI : 180/100–105 mm Hg (previous HTN), and 160–180/90–100 mm Hg in Patients (without previous HTN) Both : <180/110 mm Hg before Thrombolysis is potentially indicated

EUSI : 180/100–105 mm Hg (previous HTN), and 160–180/90–100 mm Hg in Patients (without previous HTN)

Both : <180/110 mm Hg before Thrombolysis is potentially indicated

Reperfusion of ischaemic brain IV alteplase (0·9 mg/kg, at most 90 mg), With 10% as a bolus followed by an Infusion Lasting 60 min: selected Patients within 3h of Onset of ischaemic Stroke Reduces the odds of death or Dependency at Final follow-up by 44% 110 people (50–170) from death or Dependency for every 1000 treated

IV alteplase (0·9 mg/kg, at most 90 mg), With 10% as a bolus followed by an Infusion Lasting 60 min: selected Patients within 3h of Onset of ischaemic Stroke

Reduces the odds of death or Dependency at Final follow-up by 44%

110 people (50–170) from death or Dependency for every 1000 treated

Reperfusion of ischaemic brain people whose strokes are recognised on waking ? Either streptokinase or ancrod (a defibrinating enzyme) >>> (x) 3 times, both the risk of symptomatic ICH (10% with alteplase vs 3% with placebo; absolute excess 62 per 1000 patients treated) and of fatal ICH within 7–10 days (4% vs 1%;25 per 1000 patients treated; level 1)

people whose strokes are recognised on waking ?

Either streptokinase or ancrod (a defibrinating enzyme) >>> (x)

3 times, both the risk of symptomatic ICH (10% with alteplase vs 3% with placebo; absolute excess 62 per 1000 patients treated) and of fatal ICH within 7–10 days (4% vs 1%;25 per 1000 patients treated; level 1)

Reperfusion of ischaemic brain EUSI :intra-arterial treatment of acute Middle cerebral artery occlusion with Prourokinase in a 6 h time window : Improved outcome (level II) ASA :more conservative,selected Patients,not approved by the FDA(no at Least two double-blind, placebo-Controlled, randomised trials )

EUSI :intra-arterial treatment of acute Middle cerebral artery occlusion with Prourokinase in a 6 h time window : Improved outcome (level II)

ASA :more conservative,selected Patients,not approved by the FDA(no at Least two double-blind, placebo-Controlled, randomised trials )

Reperfusion of ischaemic brain Both :intra-arterial thrombolysis of Acute basilar artery occlusion is limited

Both :intra-arterial thrombolysis of Acute basilar artery occlusion is limited

Protection of ischaemic brain cells Currently, no agent with putative Neuroprotective effects (level I)

Currently, no agent with putative Neuroprotective effects (level I)

Augmentation of cerebral blood flow Isovolaemic haemodilution Increasing cerebral perfusion pressure (eg, hypervolaemic haemodilution) Both :not been established as useful ASA :risk of serious neurological and Cardiovascular complications

Isovolaemic haemodilution

Increasing cerebral perfusion pressure (eg, hypervolaemic haemodilution)

Both :not been established as useful

ASA :risk of serious neurological and Cardiovascular complications

Prevention of early recurrent ischaemic stroke : Aspirin Within 48 h unless thrombolytic therapy Is planned (withheld for 24 h ) 160–300 mg/day reduced the odds of Recurrent stroke during the treatment Period by 13% and of death or Dependency at the end of follow-up by 5% ASA : no recommendation of other Antiplatelet drugs in acute ischaemic stroke

Within 48 h unless thrombolytic therapy Is planned (withheld for 24 h )

160–300 mg/day reduced the odds of Recurrent stroke during the treatment Period by 13% and of death or Dependency at the end of follow-up by 5%

ASA : no recommendation of other Antiplatelet drugs in acute ischaemic stroke

Prevention of early recurrent ischaemic stroke : Heparins Do not recommend routine, urgent use Of heparin, low-molecular weight Heparin, or heparinoids after ischaemic Stroke Risk of haemorrhagic transformation EUSI :cardiac sources with a high risk Of re-embolism, arterial dissection, or High grade arterial stenosis before Surgery (level IV)

Do not recommend routine, urgent use Of heparin, low-molecular weight Heparin, or heparinoids after ischaemic Stroke

Risk of haemorrhagic transformation

EUSI :cardiac sources with a high risk Of re-embolism, arterial dissection, or High grade arterial stenosis before Surgery (level IV)

Prevention of early recurrent ischaemic stroke : Heparins ASA :more conservative, does not Recommend urgent anticoagulation for Patients with moderate-to-severe stroke Because of a high risk of serious Intracranial bleeding complications

ASA :more conservative, does not Recommend urgent anticoagulation for Patients with moderate-to-severe stroke Because of a high risk of serious Intracranial bleeding complications

Revascularisation procedures ASA :no definitive data about carotid Endarterectomy, extracranial–Intracranial arterial bypass, or Endovascular treatments (eg, stent, Angioplasty, clot removal, suction Thrombectomy, and thrombolysis Assisted by laser and power Doppler) Within the first few hours to days of Acute ischaemic stroke EUSI :does not discuss these

ASA :no definitive data about carotid Endarterectomy, extracranial–Intracranial arterial bypass, or Endovascular treatments (eg, stent, Angioplasty, clot removal, suction Thrombectomy, and thrombolysis Assisted by laser and power Doppler) Within the first few hours to days of Acute ischaemic stroke

EUSI :does not discuss these

Prevention of complications : Medical complications Not proven by randomised controlled Trials : but suggested by both that early Mobilisation is favoured to prevent Complications including aspiration Pneumonia, venous thromboembolism, Decubital ulcers (pressure sores), and Contractures

Not proven by randomised controlled Trials : but suggested by both that early Mobilisation is favoured to prevent Complications including aspiration Pneumonia, venous thromboembolism, Decubital ulcers (pressure sores), and Contractures

Prevention of complications : Medical complications Infections : appropriate antibiotics ; EUSI : NG tube feeding can’t prevent Aspiration pneumonia (level IV) Venous thromboembolism : early rehydration And mobilisation, and graded external Compression stockings (level IV), and that Low dose subcutaneous heparin or low Molecular weight heparins should only be Used in patients at high risk of venous Thromboembolism (level II) by EUSI

Infections : appropriate antibiotics ; EUSI : NG tube feeding can’t prevent Aspiration pneumonia (level IV)

Venous thromboembolism : early rehydration And mobilisation, and graded external Compression stockings (level IV), and that Low dose subcutaneous heparin or low Molecular weight heparins should only be Used in patients at high risk of venous Thromboembolism (level II) by EUSI

Prevention of complications : Medical complications ASA : Subcutaneous anticoagulants to Prevent venous thromboembolism for All immobilised patients, or the use of Intermittent external graduated Compression stockings or aspirin for Patients who cannot receive Anticoagulants

ASA : Subcutaneous anticoagulants to Prevent venous thromboembolism for All immobilised patients, or the use of Intermittent external graduated Compression stockings or aspirin for Patients who cannot receive Anticoagulants

Prevention of complications : Neurological complications( Brain oedema and high intracranial pressure ) Corticosteroids have no place in Cerebral oedema and may cause IICP (level 1) Osmotherapy and hyperventilation : Condition is deteriorating secondary to High intracranial pressure, including Herniation syndromes (level IV)

Corticosteroids have no place in Cerebral oedema and may cause IICP (level 1)

Osmotherapy and hyperventilation : Condition is deteriorating secondary to High intracranial pressure, including Herniation syndromes (level IV)

Prevention of complications : Neurological complications( Brain oedema and high intracranial pressure ) External ventricular drainage or Ventriculostomy : treat IICP due to Hydrocephalus (level III) Surgical decompression and evacuation Of large cerebellar infarctions that Compress the brainstem and cause Hydrocephalus is justified (level III)

External ventricular drainage or Ventriculostomy : treat IICP due to Hydrocephalus (level III)

Surgical decompression and evacuation Of large cerebellar infarctions that Compress the brainstem and cause Hydrocephalus is justified (level III)

Prevention of complications : Neurological complications( Brain oedema and high intracranial pressure ) Surgical decompression with evacuation Of a large hemispheric infarction can be A life-Saving measure but needs further Investigation ASA :most survivors have severe Residual Neurological deficits (level III) EUSI :survivors may have residual Neurological deficit that allows an Independent life (level III)

Surgical decompression with evacuation Of a large hemispheric infarction can be A life-Saving measure but needs further Investigation

ASA :most survivors have severe Residual Neurological deficits (level III)

EUSI :survivors may have residual Neurological deficit that allows an Independent life (level III)

Prevention of complications : Neurological complications( Seizures ) Prophylactic use is not recommended (level IV) Recurrent seizures should be treated

Prophylactic use is not recommended (level IV)

Recurrent seizures should be treated

Conclusion Evidence-based, comprehensive, up-to-Date, and consistent overall Accurate diagnosis, early reperfusion, Implementation of effective therapies to Minimise recurrent stroke and Complications, and maximised Rehabilitation : improve patient Outcome

Evidence-based, comprehensive, up-to-Date, and consistent overall

Accurate diagnosis, early reperfusion, Implementation of effective therapies to Minimise recurrent stroke and Complications, and maximised Rehabilitation : improve patient Outcome

Conclusion Minor disagreements and Inconsistencies between the ASA and EUSI :1.acute treatment of particular Patients with intra-arterial thrombolysis, Heparin, and craniectomy 2.Secondary prevention with clopidogrel as a Substitute for ticlopidine; and heparin Prophylaxis of venous thromboembolism Reflect different interpretations of unreliable (level III and level IV) evidence

Minor disagreements and Inconsistencies between the ASA and EUSI :1.acute treatment of particular Patients with intra-arterial thrombolysis, Heparin, and craniectomy

2.Secondary prevention with clopidogrel as a Substitute for ticlopidine; and heparin Prophylaxis of venous thromboembolism Reflect different interpretations of unreliable (level III and level IV) evidence