What is the best treatment during the acute phase of an ischemic stroke?

Acute Ischemic Stroke Treatment

Intravenous tissue plasminogen activator (tPA) at 0.9 mg/kg (maximum 90 mg) administered within 3 hours of symptom onset is the gold standard treatment for acute ischemic stroke, with 10% given as a bolus over 1 minute and 90% infused over 60 minutes. 1, 2

Time-Critical Treatment Windows

Intravenous tPA Administration

• Within 0-3 hours: Strongly recommended (Grade 1A) - this is where the greatest benefit occurs and represents the FDA-approved window 1, 3
• Within 3-4.5 hours: Conditionally recommended (Grade 2C) - still beneficial but with diminishing returns 1, 2, 3
• Beyond 4.5 hours: Contraindicated for IV tPA (Grade 1B) - risk outweighs benefit 1, 2, 3

The earlier treatment begins, the better the outcome - every minute counts, with the goal being door-to-needle time under 60 minutes 4, 5

Endovascular Thrombectomy

• Within 6 hours: Endovascular treatment with mechanical thrombectomy using stent retrievers is recommended for large vessel occlusions (internal carotid artery, M1, M2 segments) 1
• This can be performed alone or in combination with IV tPA 1
• Extends treatment window compared to IV tPA alone, particularly for proximal anterior circulation occlusions 1

Dosing Protocol for IV tPA

Total dose: 0.9 mg/kg (maximum 90 mg total) 1, 2

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

Critical safety measure: Draw the waste dose from the bottle and verify with another nurse before connecting to IV pump to prevent accidental overdose 1

Pre-Treatment Requirements

Blood Pressure Management

For tPA-eligible patients, blood pressure must be reduced to ≤185/110 mm Hg before treatment 1, 2

• Labetalol 10-20 mg IV over 1-2 minutes, may repeat once 1
• Nicardipine 5 mg/h IV, titrate up by 2.5 mg/h every 5-15 minutes (maximum 15 mg/h) 1
• If BP cannot be controlled: Do not administer tPA 1

During and After tPA Infusion

• Monitor BP every 15 minutes for 2 hours, then every 30 minutes for 6 hours, then hourly for 16 hours 1
• Target BP: Maintain ≤180/105 mm Hg 1
• If systolic BP >180-230 mm Hg or diastolic >105-120 mm Hg: Use labetalol or nicardipine 1

Line Placement

• Insert all IV lines, Foley catheter, and necessary tubes before tPA administration 1
• This should be rapid and not delay tPA by more than a few minutes 1
• Avoid traumatic intubation - one fatal hemorrhage has been reported from this 1

Antiplatelet Therapy in Acute Phase

For Patients NOT Receiving tPA

Aspirin 160-325 mg loading dose immediately after brain imaging excludes hemorrhage and dysphagia screening is passed 1, 6

• Continue aspirin 81-325 mg daily indefinitely 1
• For dysphagic patients: 80 mg daily via enteral tube or 325 mg rectal suppository 1

For Patients Receiving tPA

Delay all antiplatelet agents for 24 hours after tPA administration until repeat imaging excludes intracranial hemorrhage 1

For Minor Stroke or High-Risk TIA

Dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel for exactly 21 days when initiated within 12-24 hours 2, 6

• Loading doses: Aspirin 160-325 mg plus clopidogrel 300-600 mg 6
• Maintenance: Aspirin 81 mg plus clopidogrel 75 mg daily for 21 days 6

Critical Exclusions and Contraindications

Absolute Contraindications to tPA

• Patients on direct oral anticoagulants (DOACs) should NOT receive tPA routinely due to substantially elevated bleeding risk 1, 2
• INR >1.5 or elevated aPTT if on heparin within 48 hours 1
• Platelet count <100,000/mm³ 1
• Blood glucose <50 mg/dL 1
• CT showing multilobar infarction (>1/3 cerebral hemisphere) 1

Special Populations

• Patients with severe strokes (NIHSS >20): Exercise caution - they may still benefit but have higher hemorrhage risk and lower overall success rates 1
• Patients >85 years: Can be treated but have lower likelihood of favorable outcome 5
• Patients with mild-moderate strokes (NIHSS <20) and age <75: Greatest potential for excellent outcomes 1, 2

Hemorrhagic Complications

Symptomatic intracranial hemorrhage occurs in 6.4% of tPA-treated patients versus 0.6% of placebo patients 1, 2

• Fatal hemorrhage rate: approximately 3% 7
• Asymptomatic hemorrhage: 8.2% within 3 days 5
• Risk increases substantially with: Protocol violations, antiplatelet use prior to stroke (3% absolute increase), dosing errors, or anticoagulation 2, 5

Common Pitfalls to Avoid

• Protocol violations occur in up to 32.6% of cases and include: treating beyond 3 hours (13.4%), giving anticoagulants within 24 hours of tPA (9.3%), and administering tPA despite BP >185 mm Hg (6.7%) 5
• Do not delay for "observation" of response to supportive care - time is brain 1
• Do not use general anesthesia for endovascular procedures unless medically necessary (airway compromise, respiratory distress, depressed consciousness) - avoid excessive hypotension 1
• Do not give anticoagulants or antiplatelets for 24 hours after tPA 1

Blood Pressure Management for Non-tPA Candidates

If NOT Eligible for Thrombolysis

• Systolic <220 mm Hg or diastolic <120 mm Hg: Observe unless end-organ damage present 1
• Systolic >220 mm Hg or diastolic 121-140 mm Hg: Labetalol 10-20 mg IV or nicardipine infusion, aim for 10-15% reduction 1
• Diastolic >140 mm Hg: Nitroprusside 0.5 μg/kg/min IV with continuous monitoring 1

Supportive Care

• Treat hypoxia, increased intracranial pressure, seizures, and hypoglycemia 1
• Manage stroke symptoms including headache, pain, agitation, nausea, and vomiting 1
• For immobilized patients: Prophylactic low-dose subcutaneous heparin or LMWH to prevent venous thromboembolism 3