What is the time frame and criteria for administering tissue plasminogen activator (tPA) to a patient with a cerebral vascular accident (CVA) or ischemic stroke?

Time Frame and Criteria for tPA Administration in Acute Ischemic Stroke

Intravenous tissue plasminogen activator (tPA) should be administered within 3 hours of symptom onset for most patients, with consideration for extended treatment up to 4.5 hours in carefully selected patients who meet additional criteria. 1, 2

Time Windows for tPA Administration

0-3 Hour Window (Standard Treatment)

• Strong recommendation for all eligible patients (Level A evidence) 1
• Number Needed to Treat (NNT) = 8 (95% CI 4 to 31) for better long-term functional outcomes 1
• No upper age limit in this window 2

3-4.5 Hour Extended Window

• May be offered to carefully selected patients (Level B recommendation) 1
• Number Needed to Treat (NNT) = 14 (95% CI 7 to 244) 1
• Additional exclusion criteria apply in this window: 2
  • Age >80 years
  • NIHSS score >25 (severe stroke)
  • History of both diabetes and prior stroke
  • Any oral anticoagulant use regardless of INR

Patient Selection Criteria

Inclusion Criteria

• Measurable neurological deficit on NIH Stroke Scale 2
• Clearly defined time of symptom onset 2
• CT scan showing no evidence of hemorrhage 2
• Blood pressure <185/110 mmHg before treatment initiation 2

Exclusion Criteria

• Rapidly improving or minor symptoms 2
• Symptoms suggestive of subarachnoid hemorrhage 2
• Seizure at onset of stroke 2
• Prior intracranial hemorrhage 2
• Major surgery or serious trauma within previous 14 days 2
• Gastrointestinal or genitourinary hemorrhage within previous 21 days 2
• Use of anticoagulants with elevated values (PT >15 seconds or INR >1.6) 2
• Platelet count <100,000/mm³ 2
• Blood glucose <50 mg/dL or >400 mg/dL 2

Risk Assessment

Risk of Symptomatic Intracranial Hemorrhage (sICH)

• 0-3 hour window: 7% absolute increase in sICH (NNH = 14; 95% CI 10 to 21) 1
• 3-4.5 hour window: Increased risk of sICH (NNH = 23; 95% CI 13 to 78) 1

Administration Protocol

1. Dose: 0.9 mg/kg (maximum 90 mg) 2
2. Administration: 10% as bolus over 1 minute, remainder over 60 minutes 2
3. Target door-to-needle time: <60 minutes in 90% of treated patients 2
   • Faster treatment is associated with better outcomes 3
   • Only 26.6% of patients receive tPA within 60 minutes of arrival 4

Post-Administration Monitoring

• Frequent neurological assessments 2
• Blood pressure monitoring every 15 minutes for 2 hours, then every 30 minutes for 6 hours 2
• Maintain BP <180/105 mmHg for 24 hours after treatment 2
• No anticoagulants or antiplatelets for 24 hours after tPA administration 2

Important Considerations

Shared Decision Making

• When feasible, discuss potential benefits and risks with patient/surrogate 1
• Patients often overestimate benefits and underestimate risks of tPA therapy 1, 2

Common Pitfalls to Avoid

1. Delaying treatment while waiting for additional imaging beyond non-contrast CT 1
   • If eligible for IV tPA, begin treatment before additional imaging or transfer for endovascular therapy
2. Inappropriate blood pressure management 2
3. Early anticoagulation (within 24 hours of tPA) 2
4. Failure to recognize stroke mimics 2
5. Treating beyond recommended time windows 2

Hospital Requirements

• Rapid access to brain imaging and interpretation 2
• Established protocols for drug administration and monitoring 2
• Ability to manage complications 2

Outcomes and Efficacy

• Treatment within 3 hours improves long-term functional outcomes 1
• Treatment within 3-4.5 hours may improve functional outcomes in selected patients 1
• Faster door-to-needle times (<60 minutes) are associated with: 3
  • Lower in-hospital mortality (8.25% vs 9.93%)
  • Reduced symptomatic intracranial hemorrhage (4.68% vs 5.68%)
  • Higher rates of discharge to home (42.7% vs 37.6%)

The time-sensitive nature of tPA administration cannot be overstated, as efficacy decreases and risks increase with longer delays from symptom onset to treatment.