What is the recommended dose and administration protocol for Tissue Plasminogen Activator (TPA) in acute ischemic stroke?

Recommended Dose and Administration Protocol for Tissue Plasminogen Activator (TPA) in Acute Ischemic Stroke

The recommended dose of intravenous tPA for acute ischemic stroke is 0.9 mg/kg (maximum 90 mg), with 10% given as an initial bolus over 1 minute followed by the remaining 90% infused over 60 minutes, administered within 4.5 hours of symptom onset. 1

Time Windows for Administration

• 0-3 hours after symptom onset: Strong recommendation for tPA administration (Grade 1A) 1, 2
• 3-4.5 hours after symptom onset: More cautious recommendation (Grade 2C) 1
• Beyond 4.5 hours: Not recommended (Grade 1B) 1, 2

Administration Protocol

1. Pre-administration requirements:

   • Confirm ischemic stroke diagnosis with brain imaging (CT or MRI)
   • Blood glucose check
   • Blood pressure must be below 185/110 mmHg 1

2. Dosing details:

   • Calculate dose: 0.9 mg/kg (maximum 90 mg)
   • Administer 10% of total dose as bolus over 1 minute
   • Infuse remaining 90% over 60 minutes 1

3. Monitoring during and after administration:

   • Neurological evaluations every 15 minutes for first 2 hours
   • Every 30 minutes for next 6 hours
   • Every hour thereafter 1
   • Monitor especially for symptomatic intracranial hemorrhage within first 12 hours 1

Exclusion Criteria for tPA Administration

Key exclusion criteria include:

• Symptom onset >4.5 hours ago or unknown onset time
• 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

Special Considerations

1. Endovascular therapy considerations:

   • Patients eligible for both IV tPA and endovascular therapy should receive IV tPA while simultaneously preparing for endovascular intervention 3
   • For patients on direct oral anticoagulants (DOACs), tPA should not be routinely administered; endovascular therapy may be considered instead 3

2. Antiplatelet therapy:

   • In patients treated with tPA, aspirin should be delayed until after the 24-hour post-thrombolysis scan has excluded intracranial hemorrhage 3
   • For patients not receiving tPA, early aspirin therapy (160-325 mg) is recommended 1, 2

Evidence on Dosing

Standard-dose tPA (0.9 mg/kg) has been shown to be more effective than lower doses. A study from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China found that patients receiving 0.85-0.95 mg/kg had better functional outcomes than those receiving lower doses (0.5-0.7 mg/kg or 0.7-0.85 mg/kg), without increased risk of symptomatic intracranial hemorrhage 4.

Efficacy and Safety Considerations

• Efficacy: When administered within 3 hours, tPA treatment results in approximately 12% absolute increase in patients with minimal or no disability (number needed to treat = 8.3) 3
• Safety risks: Symptomatic intracranial hemorrhage occurs in approximately 7% of tPA-treated patients compared to 1% in placebo groups 3
• Mortality: 90-day mortality is not significantly different between tPA and placebo groups (17% vs 21%, p=0.30) 3

Important Clinical Pearls

• Time is critical: Once the decision is made to administer IV tPA, treatment should be initiated as rapidly as possible 3
• Systems of care: The effectiveness of tPA is better established in institutions with systems in place to safely administer the medication 3
• Shared decision-making: When feasible, discussion of potential benefits and harms with the patient or surrogate is recommended prior to tPA administration 3

Remember that while the recommended dose is standardized at 0.9 mg/kg, the most critical factor for successful outcomes is minimizing the time from symptom onset to treatment initiation.