What is the protocol for managing acute ischemic stroke, including administration of tissue plasminogen activator (tPA) such as alteplase?

Acute Ischemic Stroke Protocol

Immediate Assessment and Imaging

For patients presenting with acute ischemic stroke symptoms, immediately obtain a non-contrast CT scan to exclude hemorrhage, then administer IV alteplase 0.9 mg/kg (maximum 90 mg) as soon as eligibility is confirmed, targeting door-to-needle time under 60 minutes. 1

Time-Critical Actions

• Perform non-contrast CT scan immediately upon patient arrival to exclude intracranial hemorrhage before any treatment decisions 2
• Only blood glucose testing must precede alteplase initiation - do not delay treatment for other laboratory results 1
• Obtain ECG, complete blood count, electrolytes, creatinine, INR, PTT, and troponin, but do not wait for these results before starting thrombolysis 1
• Target door-to-needle time <60 minutes in 90% of patients, with median time of 30 minutes 2, 1

IV Alteplase Administration Protocol

Dosing and Administration

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

• 10% of total dose (0.09 mg/kg) as IV bolus over 1 minute
• Remaining 90% (0.81 mg/kg) as IV infusion over 60 minutes

Critical Warning: This stroke dosing differs from myocardial infarction protocols 2

Time Windows for Treatment

0-3 Hour Window (Class I, Level A)

IV alteplase SHOULD be offered to all eligible patients within 3 hours of symptom onset to improve functional outcomes (NNT = 8.3) 2

Eligibility criteria (NINDS criteria): 2

• Age ≥18 years
• Clinical diagnosis of ischemic stroke with measurable neurological deficit
• CT scan excludes intracranial hemorrhage
• Symptom onset clearly <3 hours

3-4.5 Hour Window (Class I, Level B)

IV alteplase SHOULD be administered to eligible patients between 3-4.5 hours after symptom onset 2, 1

Additional exclusion criteria for 3-4.5 hour window (ECASS III criteria): 2

• Age >80 years
• Any oral anticoagulant use (regardless of INR)
• NIHSS score >25
• Both diabetes AND prior stroke history

Beyond 4.5 Hours (Wake-Up Strokes)

For patients with unclear time of onset >4.5 hours or wake-up strokes, IV alteplase can be beneficial if MRI shows DWI-FLAIR mismatch and treatment initiated within 4.5 hours of symptom recognition 1

Blood Pressure Management

Lower blood pressure to <185/110 mmHg BEFORE initiating alteplase in patients with acute hypertension who are otherwise eligible 1

Special Populations and Situations

Patients on Anticoagulation

• Warfarin with INR ≤1.7: Alteplase may be reasonable 1
• Direct oral anticoagulants (DOACs): Do NOT routinely administer alteplase 2, 1
  • Consider endovascular thrombectomy instead for eligible patients 2, 1
  • In comprehensive stroke centers with DOAC level testing and reversal agents available, thrombolysis could be considered with hematology consultation 2

Mild or Improving Symptoms

Within 3 hours, treatment of patients with mild non-disabling symptoms may be considered 1

Seizure at Onset

Alteplase is reasonable if evidence suggests residual impairments are from stroke, not postictal phenomenon 1

Elderly Patients (>80 years)

For patients >80 years presenting in the 3-4.5 hour window, IV alteplase is safe and can be as effective as in younger patients 1

Mechanical Thrombectomy (Endovascular Treatment)

0-6 Hour Window

Perform mechanical thrombectomy if ALL criteria met: 1

• Age ≥18 years
• Pre-stroke mRS 0-1
• ICA or MCA-M1 occlusion
• NIHSS ≥6
• ASPECTS ≥6
• Groin puncture possible within 6 hours of symptom onset

6-24 Hour Window

Mechanical thrombectomy is recommended for patients with large vessel occlusion who have: 1

• Sizable mismatch between ischemic core (CTP or DWI-MRI) and clinical deficits or hypoperfusion area (CTP or PWI-MRI)

Critical Integration Points

• Obtain CTA for suspected large vessel occlusion 1
• Administer IV alteplase even if mechanical thrombectomy is planned - do not delay alteplase 1
• Do NOT observe for clinical response after alteplase before proceeding to thrombectomy - any delay worsens outcomes 1
• Technical goal: mTICI grade 2b/3 reperfusion 1

Risks and Benefits

Benefits

• 0-3 hours: 12% absolute increase in patients with minimal/no disability (39% vs 26% achieving mRS 0-1) 2
• 3-4.5 hours: NNT = 14 for favorable outcome 2
• Reduced in-hospital mortality (8.25% vs 9.93% with faster treatment) 3

Risks

• Symptomatic intracranial hemorrhage within 36 hours: 2
  • 0-3 hours: 7% (vs 1% placebo), NNH = 17
  • 3-4.5 hours: NNH = 23
• No increase in 90-day mortality 2

Management of Complications

Angioedema

Use staged response with antihistamines, glucocorticoids, and standard airway management per local protocol 2

Alteplase-Associated Bleeding

Insufficient evidence supports routine use of cryoprecipitate, FFP, prothrombin complex concentrates, tranexamic acid, factor VIIa, or platelet transfusions - decisions should be individualized 2

Common Pitfalls to Avoid

• Do not delay treatment waiting for complete laboratory results - only glucose is mandatory before starting 1
• Do not use tenecteplase as standard therapy - it has not been proven superior or non-inferior to alteplase 1
• Do not use sonothrombolysis as adjuvant therapy - not recommended 1
• Do not wait to assess clinical response after alteplase before proceeding to thrombectomy - delays worsen outcomes 1
• Every minute matters - faster treatment correlates with better outcomes, with door-to-needle time improvements associated with reduced mortality and hemorrhage 3

Consent Considerations

Intravenous thrombolysis is considered standard of care for acute stroke treatment - routine emergency consent procedures apply 2

When feasible, shared decision-making should include discussion of potential benefits (improved functional outcomes) and harms (symptomatic ICH risk) 2