What is the recommended treatment for acute ischemic stroke thrombolysis?

Acute Ischemic Stroke Thrombolysis Management

For acute ischemic stroke, intravenous alteplase (r-tPA) at a dose of 0.9 mg/kg (maximum 90 mg) is strongly recommended as the first-line thrombolytic treatment within 4.5 hours of symptom onset, with treatment initiated as soon as possible to maximize benefits. 1

Timing and Eligibility

• IV alteplase is strongly recommended within 3 hours of symptom onset (Grade 1A evidence) 1
• IV alteplase may be administered between 3-4.5 hours of symptom onset in eligible patients (Grade 2C evidence) 1, 2
• IV alteplase is not recommended beyond 4.5 hours of symptom onset (Grade 1B evidence) 1
• Treatment should be initiated as soon as possible after patient arrival and CT scan, with a target door-to-needle time of less than 60 minutes in 90% of treated patients, and a median door-to-needle time of 30 minutes 1

Dosing Protocol

• Alteplase should be administered at 0.9 mg/kg to a maximum of 90 mg total dose 1
• 10% (0.09 mg/kg) given as an intravenous bolus over one minute 1
• Remaining 90% (0.81 mg/kg) given as an intravenous infusion over 60 minutes 1
• CAUTION: The dosing of alteplase for stroke is not the same as the dosing protocol for administration of alteplase for myocardial infarction 1

Blood Pressure Management

• Before administering alteplase, blood pressure must be below 185/110 mmHg 1
• If blood pressure exceeds these limits and cannot be controlled, alteplase should not be administered 1
• Blood pressure monitoring during and after treatment with alteplase should occur every 15 minutes during treatment and for another 2 hours, then every 30 minutes for 6 hours, and then every hour for 16 hours 1

Alternative Thrombolytic Options

• For patients with acute ischemic stroke due to proximal cerebral artery occlusions who do not meet eligibility criteria for IV alteplase, intraarterial (IA) alteplase initiated within 6 hours of symptom onset may be considered (Grade 2C) 1
• Tenecteplase (0.25 mg/kg, maximum dose 25 mg) administered as a single IV bolus might be considered as an alternative to alteplase in select patients, particularly those with large vessel occlusions 3
• IV alteplase is suggested over combination IV/IA alteplase (Grade 2C) 1

Management of Hospital Inpatients with New Stroke

• Hospital inpatients that present with sudden onset of new stroke symptoms should be rapidly evaluated by a specialist team and provided with access to appropriate acute stroke treatments (including thrombolysis and EVT) 1

Management of Complications

• For patients with angioedema, a staged response using antihistamines, glucocorticoids, and standard airway management should be used as per local protocol 1
• There is insufficient evidence to support routine use of cryoprecipitate, fresh frozen plasma, prothrombin complex concentrates, tranexamic acid, factor VIIa, or platelet transfusions for alteplase-associated bleeding 1

Special Considerations

• Patients on direct oral anticoagulants (DOACs): alteplase should not routinely be administered to patients on DOACs presenting with acute ischemic stroke 1
• In comprehensive stroke centers with access to specialized tests of DOAC levels and reversal agents, thrombolysis could be considered in consultation with hematology specialists 1
• For patients with a history of cerebral hemorrhage, alteplase is not absolutely contraindicated but requires careful risk-benefit assessment 4

Adjunctive Treatments

• Early aspirin therapy (160-325 mg) is recommended within 48 hours of stroke onset (Grade 1A) 1, 5
• For patients with restricted mobility, prophylactic-dose subcutaneous heparin (preferably LMWH) or intermittent pneumatic compression devices are recommended (Grade 2B) 1, 5
• LMWH is preferred over unfractionated heparin for prophylaxis (Grade 2B) 1, 5

Common Pitfalls and Caveats

• Delays in treatment significantly reduce the benefits of thrombolysis - every minute counts 1, 6
• Incorrect dosing of alteplase (confusing stroke protocol with myocardial infarction protocol) can lead to serious complications 1
• Inadequate blood pressure control before, during, and after thrombolysis increases the risk of intracerebral hemorrhage 1
• Failure to recognize contraindications to thrombolysis can lead to increased complications 2
• Symptomatic intracerebral hemorrhage occurs in approximately 3% of patients treated with alteplase 6