What is the recommended administration and management of Alteplase (tissue plasminogen activator) for acute ischemic stroke?

Alteplase Administration and Management for Acute Ischemic Stroke

Alteplase should be administered at a dose of 0.9 mg/kg (maximum 90 mg) with 10% given as an intravenous bolus over one minute and the remaining 90% as an infusion over 60 minutes, initiated as quickly as possible within 4.5 hours of symptom onset. 1, 2

Time Window and Patient Selection

0-3 Hour Window (Strongest Evidence)

• All eligible patients should receive IV alteplase within 3 hours of symptom onset (Class I, Level A) 1, 2
• No upper age limit applies in this time window 1
• Severe stroke symptoms are not a contraindication 1

3-4.5 Hour Window (Additional Criteria)

• Additional exclusion criteria apply:
  • Age ≤80 years
  • No history of both diabetes mellitus and prior stroke
  • NIHSS score ≤25
  • Not taking oral anticoagulants
  • No imaging evidence of ischemic injury involving more than one-third of MCA territory 1, 2

Pre-Treatment Requirements

Blood Pressure Management

• BP must be <185/110 mmHg before initiating treatment 1, 2
• BP should be maintained <180/105 mmHg for at least 24 hours after treatment 2
• Stability of BP should be assessed before starting alteplase 1

Imaging

• Non-contrast CT scan is required to rule out hemorrhage 1
• Treatment can proceed with early ischemic changes of mild to moderate extent 1
• Extensive regions of clear hypoattenuation (obvious hypodensity) are a contraindication 1

Laboratory Parameters

• Blood glucose should be >50 mg/dL before administration 1, 2
• For patients on warfarin, INR should be ≤1.7 and/or PT <15 seconds 1
• For patients on hemodialysis, normal aPTT is required 1

Monitoring During and After Administration

1. Neurological assessments and BP monitoring:

   • Every 15 minutes during infusion and for 2 hours after
   • Every 30 minutes for the next 6 hours
   • Hourly until 24 hours after treatment 2

2. If the patient develops severe headache, acute hypertension, nausea, vomiting, or worsening neurological examination:

   • Discontinue infusion immediately
   • Obtain emergency head CT scan 2

3. Follow-up CT or MRI scan at 24 hours before starting anticoagulants or antiplatelet agents 2

Management of Complications

Angioedema

• Use a staged response with antihistamines, glucocorticoids, and standard airway management per local protocol 1

Symptomatic Intracranial Hemorrhage

• There is insufficient evidence to support routine use of cryoprecipitate, fresh frozen plasma, prothrombin complex concentrates, tranexamic acid, factor VIIa, or platelet transfusions 1
• Management should be decided on an individual case basis 1

Special Considerations

Prior Antiplatelet Therapy

• Alteplase is recommended for patients on antiplatelet monotherapy or combination therapy 1
• The benefit outweighs the increased risk of symptomatic intracranial hemorrhage 1

Endovascular Thrombectomy (EVT)

• Eligible patients should receive IV alteplase even if EVT is being considered 2
• Do not wait to evaluate response to IV alteplase before proceeding with catheter angiography for EVT 2
• EVT is indicated in patients who have received IV alteplase and those not eligible for IV alteplase 1

Direct Oral Anticoagulants (DOACs)

• Alteplase should not routinely be administered to patients on DOACs 1
• In comprehensive stroke centers with specialized tests for DOAC levels and reversal agents, thrombolysis could be considered in consultation with hematology specialists 1

Common Pitfalls to Avoid

1. Incorrect dosing: The dosing of alteplase for stroke is not the same as for myocardial infarction 1

2. Delayed administration: Time is brain - every effort should be made to minimize door-to-needle time 1, 2

3. Inadequate BP control: Failure to maintain BP within recommended parameters increases bleeding risk 1, 2

4. Inadequate monitoring: Careful neurological and vital sign monitoring is essential 2

5. Early anticoagulation: Avoid starting anticoagulants or antiplatelets before the 24-hour follow-up imaging 2

6. Invasive procedures: Delay placement of nasogastric tubes, indwelling bladder catheters, or intra-arterial pressure catheters if possible 2

Recent evidence from a reanalysis of the ECASS III trial has questioned the benefit of alteplase in the 3-4.5 hour window 3, but current guidelines still support its use within this timeframe when patients meet eligibility criteria 1, 2.