What is the treatment for acute ischemic stroke?

Treatment of Acute Ischemic Stroke

For acute ischemic stroke, administer IV recombinant tissue plasminogen activator (r-tPA/alteplase) at 0.9 mg/kg (maximum 90 mg) if treatment can be initiated within 3 hours of symptom onset, with 10% given as a bolus over 1 minute and 90% infused over 60 minutes. 1

Time-Based Treatment Algorithm

Within 3 Hours of Symptom Onset

• IV r-tPA is the strongest recommendation (Grade 1A evidence) for eligible patients when treatment can be initiated within this window 1
• This represents the highest level of evidence with the greatest benefit for reducing mortality and improving functional outcomes 2, 3
• The NINDS trial demonstrated that patients treated within 3 hours were at least 30% more likely to have minimal or no disability at 3 months 4

Between 3 to 4.5 Hours of Symptom Onset

• IV r-tPA is suggested but with weaker evidence (Grade 2C) compared to the 3-hour window 1
• The ECASS III trial showed significant improvement in clinical outcomes at 90 days when alteplase was administered in this extended window 2
• However, safety and functional outcomes are less favorable in the 3-4.5 hour window compared to treatment within 3 hours 2

Beyond 4.5 Hours of Symptom Onset

• IV r-tPA is NOT recommended (Grade 1B against) when treatment cannot be initiated within 4.5 hours 1
• The ATLANTIS study found no significant benefit and increased risk of symptomatic intracerebral hemorrhage when r-tPA was given between 3-5 hours 5

Critical Pre-Treatment Requirements

Blood Pressure Management

• Blood pressure MUST be reduced and maintained below 185/110 mmHg before r-tPA administration 1, 6
• After r-tPA treatment, maintain blood pressure below 180/105 mmHg for at least 24 hours 1, 6
• For systolic >185 mmHg or diastolic >110 mmHg pre-treatment, use labetalol 10-20 mg IV over 1-2 minutes (may repeat once), or nicardipine drip 5 mg/h titrated up by 2.5 mg/h every 5-15 minutes (maximum 15 mg/h) 1
• If blood pressure cannot be controlled to these targets, do NOT administer r-tPA 1

IV Access and Preparation

• Establish all necessary IV lines before r-tPA administration 1
• Use the non-paretic arm for IV placement to preserve the affected arm for rehabilitation 4
• Insert Foley catheter and any other indwelling lines/tubes rapidly, but do not delay r-tPA by more than a few minutes 1
• Verify the calculated dose with another nurse before administration to prevent accidental overdose 1

Dosing Protocol for r-tPA

• Total dose: 0.9 mg/kg (maximum 90 mg total) 1, 6
• 10% given as IV bolus over 1 minute 1, 6
• Remaining 90% infused continuously over 60 minutes 1, 6
• Discard any remaining portion of the preparation to prevent accidental overdose 1

Adjunctive Acute Treatment

Aspirin Therapy

• Administer aspirin 160-325 mg within 48 hours of stroke onset (Grade 1A) 1
• Do NOT give aspirin within 24 hours of r-tPA administration 6
• Aspirin is preferred over therapeutic parenteral anticoagulation in the acute phase (Grade 1A) 1

VTE Prophylaxis for Immobilized Patients

• Use prophylactic-dose subcutaneous LMWH or intermittent pneumatic compression devices (Grade 2B) 1
• LMWH is preferred over unfractionated heparin (Grade 2B) 1, 7
• Do NOT use elastic compression stockings (Grade 2B against) 1, 7

Alternative Interventions for Selected Patients

Intraarterial Thrombolysis

• For patients with proximal cerebral artery occlusions who do NOT meet IV r-tPA eligibility criteria, consider intraarterial r-tPA within 6 hours of symptom onset (Grade 2C) 1
• IV r-tPA alone is preferred over combination IV/IA r-tPA (Grade 2C) 1
• Intraarterial therapy requires specially trained interventional radiologists 1

Mechanical Thrombectomy

• The 2012 ACCP guidelines suggest AGAINST routine mechanical thrombectomy (Grade 2C) 1
• However, more recent evidence (2025) indicates that endovascular thrombectomy is now recommended for patients with large vessel occlusions, including those who received IV alteplase and those ineligible for IV alteplase 6
• This represents an evolution in practice where newer trials have demonstrated benefit not captured in the older guidelines 6

Post-Treatment Monitoring

Blood Pressure Monitoring Schedule

• Check blood pressure every 15 minutes for 2 hours 1
• Then every 30 minutes for 6 hours 1
• Then every hour for 16 hours 1

Blood Pressure Management Post-r-tPA

• For diastolic >140 mmHg: sodium nitroprusside 0.5 μg/kg/min IV infusion, titrate to desired level 1
• For systolic >230 mmHg or diastolic 121-140 mmHg: labetalol 10 mg IV over 1-2 minutes, may repeat every 10-20 minutes (maximum 300 mg), or nicardipine 5 mg/h IV drip, titrate up by 2.5 mg/h every 5 minutes to maximum 15 mg/h 1

Critical Safety Considerations

Hemorrhagic Complications

• Symptomatic intracerebral hemorrhage occurs in approximately 3.3-7.0% of r-tPA treated patients 5, 3
• Fatal ICH occurs in approximately 3.0% of treated patients 5
• The risk of hemorrhage increases significantly with protocol violations, particularly treating beyond 3 hours or with uncontrolled blood pressure 3

Common Pitfalls to Avoid

• Do NOT delay treatment for difficult IV access—time is brain 4
• Do NOT administer r-tPA if blood pressure cannot be controlled below 185/110 mmHg 1
• Do NOT give aspirin or anticoagulants within 24 hours of r-tPA 6
• Do NOT use r-tPA beyond 4.5 hours from symptom onset 1, 5

Supportive Care Measures

• Provide supplemental oxygen to maintain saturation >94% 6
• Treat hyperthermia (temperature >38°C) and identify sources 6
• Correct hypovolemia with IV normal saline 6
• Treat hypoglycemia (blood glucose <60 mg/dL) immediately, with target normoglycemia 6
• For hyperglycemia, target blood glucose 140-180 mg/dL 6