What is the recommended dosage and administration of tissue plasminogen activator (tPA) for acute ischemic stroke and pulmonary embolism?

Recommended Dosage and Administration of tPA for Acute Ischemic Stroke and Pulmonary Embolism

For acute ischemic stroke, tPA should be administered at 0.9 mg/kg (maximum 90 mg) with 10% given as a bolus and the remaining 90% infused over 60 minutes within 3 hours of symptom onset, while for pulmonary embolism, tenecteplase at 0.25 mg/kg (maximum 25 mg) as a single IV bolus is recommended. 1, 2

Acute Ischemic Stroke

Dosage and Administration

• tPA (alteplase) should be administered at 0.9 mg/kg (maximum dose 90 mg) for acute ischemic stroke 1
• Administration protocol: 10% of the total dose given as a bolus, followed by the remaining 90% infused over 60 minutes 1
• Treatment should be initiated as rapidly as possible once the decision is made 1

Time Windows

• 0-3 hours: Level A recommendation (strongest evidence) for improved functional outcomes 1
• 3-4.5 hours: Level B recommendation with additional exclusion criteria (age >80, NIHSS >25, oral anticoagulant use, or history of both diabetes and prior stroke) 1
• Beyond 4.5 hours: Not recommended (Grade 1B) 1

Efficacy and Safety

• Within 0-3 hours: Number needed to treat (NNT) = 8.3 for favorable outcome 1
• Within 3-4.5 hours: NNT = 14 (95% CI 7 to 244) 1
• Risk of symptomatic intracerebral hemorrhage (sICH): 7% with tPA vs 1% with placebo within 36 hours 1
• Despite increased sICH risk, 3-month mortality is not significantly different between tPA and placebo groups (17% vs 21%, p=0.30) 1

Patient Selection

• Patients should meet NINDS inclusion/exclusion criteria for the 0-3 hour window 1
• Patients should meet ECASS III inclusion/exclusion criteria for the 3-4.5 hour window 1
• Benefit is most consistent in patients with NIHSS scores between 5-22 3

Alternative Thrombolytic for Stroke: Tenecteplase

• Tenecteplase may be considered as an alternative to alteplase at a dose of 0.25 mg/kg (maximum 25 mg) administered as a single IV bolus 2
• Advantages include single-bolus administration due to longer half-life (90-130 minutes) 2
• Particularly beneficial for patients with large vessel occlusions and those being considered for endovascular therapy or transfer 2

Common Pitfalls to Avoid

• Delaying treatment while waiting for improvement in patients with mild symptoms - earlier treatment is associated with better outcomes 3
• Excluding patients based solely on age - elderly patients can benefit from tPA despite having higher baseline risk 3
• Administering tPA beyond the recommended time windows - risk significantly outweighs benefit beyond 4.5 hours 1
• Failing to recognize that tPA effectiveness may be less established in institutions without proper systems in place 1

Decision Algorithm for Acute Ischemic Stroke

1. Determine precise time of symptom onset 3
2. Perform rapid neurological assessment including NIHSS score 3
3. Obtain emergent CT scan to rule out hemorrhage 1
4. For patients within 0-3 hours:
   • Administer tPA 0.9 mg/kg (max 90 mg) if no contraindications 1
   • 10% as bolus, 90% over 60 minutes 1
5. For patients within 3-4.5 hours:
   • Apply additional exclusion criteria 1
   • If eligible, administer same dosing regimen 1
6. For patients with large vessel occlusion:
   • Consider tenecteplase 0.25 mg/kg (max 25 mg) as single bolus 2

Pulmonary Embolism

While the provided evidence focuses primarily on stroke treatment, tenecteplase is recommended for pulmonary embolism at a dose of 0.25 mg/kg (maximum 25 mg) administered as a single IV bolus 2. This single-bolus administration offers significant workflow advantages due to its longer half-life of 90-130 minutes compared to the 60-minute infusion required for alteplase in stroke treatment 2.