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

rtPA Dosing for Acute Ischemic Stroke

The recommended dose of recombinant tissue plasminogen activator (rtPA) for acute ischemic stroke is 0.9 mg/kg (maximum 90 mg total), with 10% administered as an intravenous bolus over 1 minute and the remaining 90% infused over 60 minutes. 1, 2

Standard Dosing Protocol

Calculate the total dose as 0.9 mg/kg based on actual body weight, not to exceed 90 mg maximum regardless of patient weight. 1, 2

The administration follows this specific sequence:

• Initial bolus: 10% of total calculated dose given IV over 1 minute 1, 2
• Continuous infusion: Remaining 90% infused over 60 minutes 1, 2

For example, a 70 kg patient receives 63 mg total (70 × 0.9), with 6.3 mg as bolus and 56.7 mg over 60 minutes. 2

Time Window for Administration

The strength of recommendation varies by time from symptom onset:

• Within 3 hours: Strong recommendation (Grade 1A) - This represents the highest level of evidence and strongest benefit 1, 2
• Between 3-4.5 hours: Conditional recommendation (Grade 2C) - Treatment may still be beneficial but with less certainty 1, 2
• Beyond 4.5 hours: Contraindicated (Grade 1B) - Do not administer IV rtPA 1

The evidence strongly supports earlier treatment, with patients treated within 90 minutes showing greater benefit (odds ratio 2.11) compared to those treated at 90-180 minutes (odds ratio 1.69). 2

Evidence Supporting This Dose

This 0.9 mg/kg dose is NOT arbitrary - it is the only dose proven effective in the landmark NINDS trial and validated across multiple guidelines. 1, 3

Research comparing different doses confirms that lower doses are inferior. A Chinese study (TIMS-China) with 919 patients demonstrated that doses of 0.5-0.7 mg/kg resulted in significantly worse functional outcomes (41.89% excellent recovery) compared to the standard 0.85-0.95 mg/kg dose (53.83% excellent recovery), without any reduction in bleeding risk. 4

The ATLANTIS trial definitively showed that rtPA administered between 3-5 hours provides no benefit and increases symptomatic intracranial hemorrhage from 1.1% to 7.0% (P<0.001), reinforcing the critical importance of the time window. 5

Critical Safety Parameters

Blood pressure must be reduced to <185/110 mm Hg BEFORE initiating rtPA, or the drug is absolutely contraindicated. 2, 6

For blood pressure control use:

• Labetalol 10-20 mg IV over 1-2 minutes (may repeat once), OR
• Nicardipine drip starting at 5 mg/h, titrated by 2.5 mg/h every 5-15 minutes (maximum 15 mg/h) 6

If blood pressure cannot be controlled below these thresholds despite aggressive treatment, do not administer rtPA. 2, 6

Post-Administration Monitoring

Blood pressure monitoring follows a strict protocol:

• Every 15 minutes during infusion and for 2 hours after 1, 2
• Every 30 minutes for the next 6 hours 1, 2
• Hourly for 16 hours thereafter 2

Maintain blood pressure <180/105 mm Hg throughout the monitoring period. 2

Neurological assessments must be performed:

• Every 15 minutes during infusion 1, 6
• Every 30 minutes for 6 hours after 1
• Hourly until 24 hours post-treatment 1

Absolute Contraindications Related to Anticoagulation

Do NOT administer rtPA to patients currently taking direct oral anticoagulants (DOACs) such as apixaban, rivaroxaban, or dabigatran - this is a critical safety issue. 7

The combination of systemic anticoagulation with rtPA substantially elevates bleeding risk beyond the baseline 4-6% symptomatic intracranial hemorrhage rate. 7 Standard coagulation tests (PT/INR, aPTT) do not reliably measure DOAC levels and cannot be used to guide rtPA decisions. 7

Delay all anticoagulants and antiplatelet agents for 24 hours after rtPA administration. 1, 6

Expected Hemorrhage Rates

With proper dosing and patient selection:

• Symptomatic intracranial hemorrhage: 6.4% (versus 0.6% with placebo) 2, 6
• Fatal intracranial hemorrhage: 3.0% (versus 0.3% with placebo) 5

These rates increase substantially with protocol violations, including incorrect dosing, treatment beyond the time window, or administration to anticoagulated patients. 2, 7

Common Pitfalls to Avoid

Never round up to convenient numbers - calculate the exact 0.9 mg/kg dose and maximum of 90 mg. 1, 2

Never use weight >100 kg for dose calculation - cap the weight at 100 kg (giving maximum 90 mg dose) even if patient weighs more. 6

Never delay rtPA to obtain vascular imaging if the patient meets clinical criteria for thrombolysis within the time window. 6 However, obtain CT angiography when feasible as it identifies large vessel occlusions that may benefit from mechanical thrombectomy. 2, 6

Never administer aspirin or other antiplatelets within 24 hours of rtPA - wait for follow-up CT at 24 hours to exclude hemorrhage before starting antiplatelet therapy. 1