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

Recommended Loading Dose of tPA for Acute Ischemic Stroke

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

Administration Protocol

1. Dosing calculation:

   • Calculate dose based on patient's actual body weight
   • Total dose: 0.9 mg/kg (maximum 90 mg)
   • Initial bolus: 10% of total dose given over 1 minute
   • Remaining 90% of dose: Administered as IV infusion over 60 minutes

2. Timing considerations:

   • Treatment must be initiated within 3 hours of symptom onset for strongest evidence
   • Selected eligible patients may receive treatment within 3-4.5 hours
   • Door-to-needle time target: <60 minutes in 90% of patients (median 30 minutes)
   • Treatment beyond 4.5 hours is not recommended 1

Contraindications and Precautions

Before administering tPA, ensure the patient does not have any of these contraindications:

• Symptom onset >4.5 hours or unknown time of onset
• Another stroke or serious head injury within preceding 3 months
• Major surgery within prior 14 days
• History of intracranial hemorrhage
• Gastrointestinal or genitourinary hemorrhage within previous 21 days 1

Blood Pressure Management

• Blood pressure must be <185/110 mmHg before initiating thrombolysis
• Maintain BP below 180/105 mmHg during and for 24 hours after treatment
• Administer antihypertensive medications as needed to maintain target BP 1

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 1

Antiplatelet Therapy Considerations

• Aspirin (160-325 mg) should be delayed for 24 hours in patients treated with tPA
• Antiplatelet agents should be initiated only after the 24-hour post-thrombolysis scan has excluded intracranial hemorrhage 1

Complications Management

• Monitor for angioedema and manage with antihistamines, glucocorticoids, and standard airway management if needed
• Bleeding complications require individualized management approaches 1

Clinical Evidence and Efficacy

The NINDS trial demonstrated that despite an increased risk of symptomatic intracerebral hemorrhage (6.4% with tPA vs 0.6% with placebo), treatment with tPA within 3 hours of stroke onset improved clinical outcomes at 3 months 2. Follow-up studies have confirmed the feasibility, safety, and efficacy of the 0.9 mg/kg dosing regimen when treatment guidelines are carefully followed 3.

Common Pitfalls to Avoid

• Exceeding the maximum dose of 90 mg regardless of patient weight
• Administering the entire dose as a bolus rather than the 10% bolus/90% infusion protocol
• Delaying treatment due to unnecessary tests (rapid neuroimaging with non-contrast CT is the priority)
• Failing to maintain strict blood pressure control before, during, and after tPA administration
• Administering antiplatelet agents too early (before 24-hour post-treatment scan)

The evidence strongly supports this dosing regimen, which has been consistently recommended by the American Heart Association/American Stroke Association and the Canadian Stroke Best Practice Recommendations 1.