What is the recommended loading dose of alteplase (tissue plasminogen activator, tPA) for acute ischemic stroke?

Recommended Loading Dose of Alteplase for Acute Ischemic Stroke

The recommended loading dose of alteplase for acute ischemic stroke is 0.9 mg/kg with a maximum dose of 90 mg, administered as a 10% bolus (0.09 mg/kg) over one minute followed by the remaining 90% (0.81 mg/kg) as an intravenous infusion over 60 minutes. 1, 2

Dosing Protocol Details

• Total dose: 0.9 mg/kg (maximum 90 mg)
• Initial bolus: 10% of total dose (0.09 mg/kg) given over 1 minute
• Remaining infusion: 90% of total dose (0.81 mg/kg) given over 60 minutes

This dosing protocol is strongly supported by multiple high-quality guidelines, including the 2018 Canadian Stroke Best Practice Recommendations 1 and the 2018 American Heart Association/American Stroke Association Guidelines 1.

Administration Timing

• Primary window: Within 3 hours of symptom onset (strongest evidence) 1, 2
• Extended window: 3-4.5 hours of symptom onset (for eligible patients) 1
• Door-to-needle target: Less than 60 minutes in 90% of treated patients, with a median time of 30 minutes 1

Important Considerations

Blood Pressure Management

• Blood pressure must be <185/110 mmHg before initiating alteplase 2
• Maintain BP <180/105 mmHg during and for 24 hours after treatment 2

Post-Administration Monitoring

• Neurological assessments should be performed:
  • Every 15 minutes during infusion and for 2 hours
  • Every 30 minutes for the next 6 hours
  • Hourly until 24 hours after treatment 2

Antiplatelet Therapy Timing

• In patients treated with alteplase, initiation of antiplatelet agents (such as aspirin) should be delayed until after the 24-hour post-thrombolysis scan has excluded intracranial hemorrhage 1, 2

Alternative Dosing Considerations

While the standard dose of 0.9 mg/kg is the established protocol, a 2016 study (ENCHANTED trial) investigated a lower dose of 0.6 mg/kg. This study found that the lower dose did not meet noninferiority criteria for the primary outcome of death and disability at 90 days, despite showing fewer symptomatic intracerebral hemorrhages 3. Therefore, the standard dose remains recommended.

Common Pitfalls to Avoid

1. Dosing confusion: The alteplase dosing for stroke is different from the protocol used for myocardial infarction 1

2. Delayed administration: Treatment should be initiated as soon as possible after patient arrival and CT scan, as earlier treatment is associated with better outcomes 1

3. Inappropriate antiplatelet timing: Administering aspirin before the 24-hour post-thrombolysis scan in patients who received alteplase increases bleeding risk 1

4. Inadequate monitoring: Failure to closely monitor for complications such as angioedema or hemorrhage during and after alteplase administration 2

The evidence consistently supports the 0.9 mg/kg dosing regimen (10% bolus, 90% infusion) as the standard of care for acute ischemic stroke treatment with alteplase.