What is the administration protocol for recombinant tissue plasminogen activator (rtPA) for acute ischemic stroke?

rtPA Administration Protocol for Acute Ischemic Stroke

Administer rtPA at 0.9 mg/kg (maximum 90 mg total) with 10% given as an IV bolus over 1 minute, followed by the remaining 90% infused over 60 minutes. 1, 2

Pre-Administration Requirements

Blood Pressure Control

• Blood pressure MUST be reduced to <185/110 mm Hg before initiating rtPA, or the drug should not be given. 1
• For systolic >185 mm Hg or diastolic >110 mm Hg: Give labetalol 10-20 mg IV over 1-2 minutes (may repeat once) OR nicardipine drip starting at 5 mg/h, titrated up by 2.5 mg/h every 5-15 minutes to maximum 15 mg/h 1, 3
• If blood pressure cannot be controlled below these thresholds, rtPA is contraindicated 1

Line Placement Before rtPA

• Insert ALL necessary IV lines, Foley catheter, endotracheal tube (if needed), and other indwelling devices BEFORE starting rtPA to minimize trauma and bleeding risk. 1
• Line placement should be rapid and not delay rtPA by more than a few minutes 1
• Fatal hemorrhage from traumatic intubation has been reported, so proceed carefully but expeditiously 1

Dose Calculation and Preparation

Weight-Based Dosing

• Calculate total dose: patient weight in kg (maximum 100 kg) × 0.9 mg/kg 1
• Maximum total dose is 90 mg regardless of actual weight 1, 2
• Obtain the most accurate weight possible—overdosing due to weight overestimation increases symptomatic ICH risk, particularly in the highest dose quintile (16.5% vs 9.3%, P=.025). 4

Reconstitution Protocol

• rtPA comes as crystalline powder reconstituted with sterile water to yield 100 mg total 1
• Draw the waste dose from the bottle and verify the waste amount with another nurse before connecting to IV pump tubing to prevent accidental overdose. 1
• Discard the unused portion that will not be infused 1

Administration Sequence

Bolus Dose

• Give 10% of total calculated dose as IV bolus over exactly 1 minute 1, 2
• Example: For 81 kg patient, total dose = 72.9 mg; bolus = 7.3 mg over 1 minute 2

Continuous Infusion

• Administer remaining 90% as continuous IV infusion over 60 minutes 1, 2
• Example: For same patient, infuse 65.6 mg over 60 minutes 2

Post-Administration Monitoring

Blood Pressure Surveillance

• Monitor blood pressure every 15 minutes during infusion and for 2 hours after, then every 30 minutes for 6 hours, then hourly for 16 hours. 1, 3
• Maintain blood pressure <180/105 mm Hg during and after treatment 1

Neurological Assessment

• Perform neurological checks every 15 minutes during rtPA infusion and for 2 hours after 3
• Continue every 30 minutes for 6 hours, then hourly for 16 hours 3
• Obtain urgent head CT if patient develops acute neurological deterioration, severe headache, acute hypertension, nausea, or vomiting. 3

Medication Restrictions

• Do NOT give anticoagulants or antiplatelet agents for 24 hours after rtPA administration. 1
• Aspirin 160-325 mg can be started 24-48 hours after rtPA if no hemorrhage on follow-up imaging 2, 5

Time Window Considerations

Treatment Urgency

• 0-3 hours from symptom onset: Strong recommendation for rtPA (Grade 1A) 2, 3
• 3-4.5 hours from symptom onset: Conditional recommendation (Grade 2C) 2, 3
• Beyond 4.5 hours: Contraindicated (Grade 1B) 2
• Earlier treatment within 90 minutes provides greatest benefit (odds ratio 2.11 vs 1.69 for 90-180 minutes). 1

Critical Contraindications

Anticoagulation Status

• Patients on direct oral anticoagulants (DOACs) like apixaban should NOT receive rtPA due to substantially elevated bleeding risk. 5
• Standard coagulation tests (PT/INR, aPTT) do not reliably measure DOAC levels and should not guide decisions 5
• Consider mechanical thrombectomy instead for DOAC patients with large vessel occlusion 5

Blood Pressure Threshold

• If systolic remains >185 mm Hg or diastolic >110 mm Hg despite treatment, rtPA is absolutely contraindicated 1

Expected Complications

Hemorrhage Risk

• Symptomatic intracranial hemorrhage occurs in 6.4% of rtPA-treated patients vs 0.6% of placebo patients 1, 2
• Baseline symptomatic ICH rate is 4-6% with proper dosing 2, 3
• Patients on antiplatelet therapy have 3% absolute increased risk of symptomatic ICH 2

Orolingual Angioedema

• Occurs in 1.3-5.1% of rtPA patients, more common with ACE inhibitor use 3
• If develops: Give IV ranitidine, diphenhydramine, and methylprednisolone 3

Alternative Approach: Intra-arterial Thrombolysis

• Intra-arterial rtPA extends treatment window to 6 hours after symptom onset in selected cases 1
• Requires specially trained interventional radiologists 1
• Delivers higher thrombolytic concentrations directly into thrombus 1
• Consider for patients beyond IV window or with contraindications to IV therapy 1