What is the time frame for tissue plasminogen activator (tPA) administration in an adult acute ischemic stroke patient?

Time Frame for tPA Administration After Stroke

IV tPA should be offered to acute ischemic stroke patients within 3 hours of symptom onset (strongest evidence, Level A recommendation), and may be given to carefully selected patients between 3 to 4.5 hours after symptom onset (Level B recommendation), but should NOT be administered beyond 4.5 hours. 1

Evidence-Based Time Windows

0-3 Hour Window (Strongest Recommendation)

• This is the FDA-approved time window with Level A evidence supporting improved functional outcomes, with an absolute benefit of 13% for excellent outcomes (NNT=8) 1, 2
• Patients meeting NINDS inclusion/exclusion criteria should be offered IV tPA at 0.9 mg/kg (maximum 90 mg) within this window 1
• The benefit is highly time-dependent: treatment within 0-90 minutes yields an odds ratio of 2.55 for good outcome, compared to 1.64 for 91-180 minutes 2, 3
• Once the decision is made to treat, administer tPA as rapidly as possible within any time window 1

3-4.5 Hour Window (Conditional Recommendation)

• IV tPA may be offered to carefully selected patients meeting ECASS III criteria in this extended window (Level B recommendation) 1
• The benefit is smaller but clinically meaningful (NNT=14) compared to the 0-3 hour window 1, 3
• This use remains off-label in the United States as the FDA has not approved this expanded indication, though professional organizations support it 1, 4
• The risk of symptomatic intracranial hemorrhage increases (NNH=23) in this window 1

Beyond 4.5 Hours (Contraindicated)

• Do NOT administer IV tPA beyond 4.5 hours of symptom onset (Grade 1B recommendation against use) 2, 3
• The ATLANTIS trial demonstrated no significant benefit and increased hemorrhagic complications when tPA was given between 3-5 hours 5

Critical Implementation Points

Dosing Protocol

• Administer 0.9 mg/kg (maximum 90 mg total): 10% as IV bolus over 1 minute, remaining 90% infused over 60 minutes 1, 2, 3

Pre-Treatment Requirements

• Blood pressure must be reduced to <185/110 mmHg before initiating tPA; if this cannot be achieved, tPA is contraindicated 2, 3
• Obtain non-contrast CT immediately to exclude hemorrhagic stroke 3

Risk-Benefit Considerations

• Symptomatic intracranial hemorrhage occurs in 6.4% of tPA-treated patients versus 0.6% of placebo patients within 3 hours 1, 2, 6
• The risk increases to 7-11% when treating in the 3-4.5 hour window 1
• Earlier treatment provides substantially greater benefit: every minute counts 2, 3

Common Pitfalls to Avoid

• Do not delay treatment to obtain "perfect" imaging - non-contrast CT to exclude hemorrhage is sufficient; time is brain 3
• Do not exclude patients with minor strokes - they may still benefit significantly from treatment 3
• Never administer tPA to patients on direct oral anticoagulants (DOACs) - this is an absolute contraindication due to substantially elevated bleeding risk 2, 3
• Do not give anticoagulants or antiplatelet agents for 24 hours after tPA administration 2, 3, 6