• i.v. rt-PA (0.9 mg/kg) with 10% of the dose given as bolus followed by an infusion lasting 60 minutes within 3 hours of onset of ischaemic stroke
• i.v. administration of streptokinase outside randomised, controlled clinical trials is not indicated for the management of ischaemic stroke
• Before thrombolytic therapy the diagnosis has to be established by brain CT scanning
• Thrombolytic therapy should not be given unless the emergent ancillary care and facilities to handle bleeding complications are readily available

• Preferred therapeutic approach to achieve rapid thrombolysis are plasminogen activators especially rt-PA
• Benefit has been shown individually for therapy with streptokinase, anistreplase and alteplase
• Patients treated within 12 hours who are eligible for thrombolytics should expeditiously receive either frontloaded rt-PA or streptokinase
• In an overview of nine RCTs involving more than 1000 patients, a highly significant 18% proportional reduction in mortality was observed

• Aspirin (160-300 mg) should be given as soon as possible after the onset of stroke symptoms if a diagnosis of haemorrhage is considered unlikely
• Thrombolytic treatment with tissue plasminogen activator (t-PA) should only be given provided that it can be administerd within 3 hours of the onset of stroke symptoms, that haemorrhage has been definitively excluded, and that the patient is in a specialist centre with appropriate experience and expertise
• No other drug treatment aimed at treatment of the stroke should be given unless as part of an RCT

• i.v. recombinant tissue plasminogen activator (rt-PA) within 3 hours after onset of symptoms in patients with acute stroke is a highly effective evidence-based treatment
  • Prolyse in Acute Cerebral Thromboembolism II
  • i.v. rt-PA given within 6 hours after the onset of an ischaemic stroke may be beneficial, but the benefit is smaller while the risks are higher

• 1. i.v. rt-PA (0.9 mg/kg; max 90 mg, 10 % bolus, followed by 60 min infusion) is recommended within 3 hours after stroke onset (Level I) in eligible patients
• 2. i.v. rt-PA is contra-indicated when time of onset is uncertain
• 3. i.v. streptokinase is not indicated for the management of people with ischaemic stroke (Level I)
• 4. Acute intracranial vessel occlusion may be treated with intra-arterial therapy using rt-PA or urokinase in selected patients (Level IV)

• Within the 3 hour time window
  • Stroke severity
    - Probably not for mild stroke < 4NIHSS
    - Probably not for severe stroke > 20-25   NIHSS
    
  • CT-ECASS (European Cooperative Acute Stroke Study) criteria
  • Proof of vessel occlusion not required
  • Licence restricts by age (< 80 years) and cautions use if diabetes + previous stroke
  • Licence mandates monitoring in SITS-MOST (Safe implementation of thrombolysis in stroke monitoring study)

• Suspected stroke victims should be transported without delay to the nearest medical centre with an available stroke unit (level I)
• Once stroke symptoms are suspected, patients or their proxies should call the Emergency Medical System (level III)
• Patients with subarachnoid haemorrhage should be referred urgently to a medical centre with facilities for neurosurgical and neuroradiological interventions and neurointensive care (level I)

• CCT is mandatory in patients with suspected stroke (Level III)
• MRI is recommended for selected stroke patients, where available (Level IV)
• Early evaluation of physiological parameters, blood chemistry and haematology, and cardiac function (ECG, pulse oximetry, chest x-ray) is recommended in the management of acute stroke patients (Level IV)

• Intravenous rt-PA (0.9 mg/kg; max 90 mg, 10 % bolus, followed by 60 min infusion) is recommended within 3 hours after stroke onset (Level I) in eligible patients
• Intravenous rt-PA is contraindicated when time of onset is uncertain
• Intravenous streptokinase not indicated for the management of persons with ischaemic stroke (Level I)
• Acute intracranial vessel occlusion may be treated with intra-arterial therapy using rt-PA or prourokinase in selected patients (Level IV)

• EDs and hospitals should work with emergency medical services and the community so that all parties know what the hospital's capabilities are regarding acute stroke care.
• Further studies are needed to define more clearly those patients most likely to benefit from fibrinolytic therapy in acute ischaemic stroke.
• Intravenous tPA may be an efficacious therapy for the management of acute ischaemic stroke if properly used incorporating the guidelines established by the National Institute of Neurological Disorders and Stroke (NINDS).
• There is insufficient evidence at this time to endorse the use of intravenous tPA in clinical practice when systems are not in place to ensure that the inclusion/exclusion criteria established by the NINDS guidelines for tPA use in acute stroke are followed. Therefore, the decision for an ED to use intravenous tPA for acute stroke should begin at the institutional level with commitments from hospital administration, the ED, neurology, neurosurgery, radiology, and laboratory services to ensure that the systems necessary for the safe use of fibrinolytic agents are in place.

• We recommend administration of IV t-PA in a dose of 0.9 mg/kg (maximum of 90 mg), with 10% of the total dose given as an initial bolus and the remainder infused over 60 min for eligible patients (see inclusion and exclusion criteria listed below), provided that treatment is initiated within 3 h of clearly defined symptom onset (Grade 1A recommendation).
• Underlying values and preferences: This recommendation assumes a relatively higher value on long-term functional improvement and a relatively lower value on minimising the risk of ICH in the immediate peristroke period.
• For patients with extensive (more than one third of the MCA territory) and clearly identifiable hypodensity on CT, we recommend against thrombolytic therapy (Grade 1B recommendation).

ACCP Guidelines for Acute Ischaemic Stroke Thrombolytic Therapy

Thrombolytic Therapy – AIS Treatment Within 3 to 6 h of Symptom Onset

• We do not recommend use of IV t-PA for treatment of acute ischaemic stroke of > 3h but < 6 h in unselected patients (Grade 2A recommendation). This treatment remains investigational.
• We do not recommend that clinicians use streptokinase for the treatment of acute ischaemic stroke except within the confines of a clinical trial (Grade 1A recommendation).
• In carefully selected patients with angiographically demonstrated MCA occlusion and no signs of major early infarction on the baseline CT scan who can be treated within 6 h of symptom onset, we recommend the use intra-arterial thrombolytic therapy for ischaemic stroke (Grade 2C recommendation).

Reference:
Albers et al. Chest 2004; 126 (Suppl): 438S-512S.

International Guidelines Acute Stroke Recommendations

AHA

ACCP

RCP

EUSI

ACEP

ASA

ASA (no dosage given) within 24-48h Grade A

160 to 325 mg/d for patients not receiving thrombolysis or anticoagulation

160-300 mg as soon as possible

ASA (100-300 mg) should be given within 48h (Level I)

rt-PA

i.v. 0.9 mg/kg; max dose 90 mg; patients < 3h

i.v. 0.9 mg/kg; max dose 90 mg; patients < 3h; 10% initial bolus; remaining dose over 60 min; Grade 1A not for patients 3-6h? Grade 2A CT exclusion! Grade 1B

for patients < 3h; haemorrage definitively excluded;.patient in specialist centre

i.v. 0.9 mg/kg; max dose 90 mg; patients < 3h; 10% initial bolus Level I; 3-4.5h benefit present in selected pat; Level II not when onset is uncertain

may be efficient when use follows NINDS guidelines

Current guidelines for acute stroke management, such as the European Stroke Initiative (EUSI) recommendations and the American Stroke Association guidelines recommend the use of intravenous rt-PA within 3 hours of onset of ischaemic stroke as Level 1 and Class A recommendation. While the US guidelines call the use after 3h "undecided", the EUSI guidelines give it a Level I recommendation "for selected patients". This is also reflected in the German Neurological society guidelines and also in the Royal College of Physicians' guidelines in the UK.

Reference:
Hacke W. ESC Mannheim 2004, updated by Kreutz J.