What is the recommended thrombolysis protocol for acute ischemic stroke?

Thrombolysis Protocol for Acute Ischemic Stroke

Standard IV Alteplase Protocol

Administer IV alteplase at 0.9 mg/kg (maximum 90 mg total dose) with 10% given as an IV bolus over 1 minute and the remaining 90% infused over 60 minutes for patients presenting within 3 hours of symptom onset. 1, 2, 3

Time Windows for Treatment

• 0-3 hours from symptom onset: Strong recommendation for IV alteplase (Grade 1A evidence) 1, 2
• 3-4.5 hours from symptom onset: Conditional recommendation for IV alteplase (Grade 2C evidence) 1, 2, 3
• Beyond 4.5 hours: IV alteplase is contraindicated 3

The earlier treatment is initiated, the greater the benefit—every minute counts in stroke management. 4, 5

Pre-Treatment Requirements

Blood pressure must be reduced to ≤185/110 mm Hg before initiating alteplase. 1, 2, 3

• If systolic BP >185 mm Hg or diastolic >110 mm Hg, administer labetalol 10-20 mg IV over 1-2 minutes (may repeat once) or nicardipine drip starting at 5 mg/h, titrated up by 2.5 mg/h every 5-15 minutes (maximum 15 mg/h) 6
• If blood pressure cannot be controlled below 185/110 mm Hg, do not administer alteplase 6, 3

Complete non-contrast head CT within 45 minutes of emergency department arrival to exclude intracranial hemorrhage. 2

Critical Procedural Steps

Insert all necessary IV lines, Foley catheters, and other indwelling tubes BEFORE alteplase administration to minimize bleeding risk. 6

Initiate treatment as rapidly as possible after CT scan completion—target door-to-needle time of 30 minutes, with 90% of treated patients meeting this benchmark. 1

Dosing Caution

The dosing protocol for stroke (0.9 mg/kg) differs significantly from myocardial infarction dosing—do not confuse these protocols. 1

Post-Thrombolysis Monitoring

Perform neurological assessments every 15 minutes during alteplase infusion and for 2 hours after, then every 30 minutes for 6 hours, then hourly for 16 hours. 6, 3

Monitor blood pressure every 15 minutes for 2 hours, then every 30 minutes for 6 hours, then hourly for 16 hours after infusion. 3

Obtain urgent head CT if the patient develops acute neurological deterioration, severe headache, acute hypertension, nausea, or vomiting. 6

Hemorrhagic Complications

Symptomatic intracranial hemorrhage occurs in approximately 6.4% of alteplase-treated patients versus 0.6% in placebo patients. 1, 6, 3 Risk factors include:

• NIHSS score >20 1
• Early CT changes of infarction 1
• Advanced age with severe stroke 1

There is insufficient evidence to support routine use of cryoprecipitate, fresh frozen plasma, prothrombin complex concentrates, tranexamic acid, factor VIIa, or platelet transfusions for alteplase-associated bleeding—use these on an individual case basis only. 1

Angioedema Management

Orolingual angioedema occurs in 1.3-5.1% of alteplase patients, more commonly with concurrent ACE inhibitor use. 6

If angioedema develops, administer IV ranitidine, diphenhydramine, and methylprednisolone per local protocol. 1, 6

Antiplatelet Therapy Timing

Delay all antiplatelet agents for 24 hours after alteplase administration until repeat imaging excludes intracranial hemorrhage. 3

For patients NOT receiving alteplase, administer aspirin 160-325 mg immediately after brain imaging excludes hemorrhage and dysphagia screening is passed. 1, 3

Absolute Contraindications

• Intracranial hemorrhage on CT or MRI 2
• INR >1.5 3
• Elevated aPTT 3
• Platelet count <100,000/mm³ 3
• Blood glucose <50 mg/dL 3
• CT showing multilobar infarction (>1/3 cerebral hemisphere) 3

Special Populations

Do not routinely administer alteplase to patients on direct oral anticoagulants (DOACs) due to substantially elevated bleeding risk. 1, 3 In comprehensive stroke centers with access to specialized DOAC level testing and reversal agents, thrombolysis could be considered on an individual basis in consultation with hematology specialists. 1

Pregnancy is a relative rather than absolute contraindication—alteplase may be considered in life-threatening situations. 2

Endovascular Thrombectomy (EVT)

EVT is indicated for patients with large vessel occlusions within 6 hours of symptom onset, regardless of whether they received IV alteplase. 1, 6

Patients eligible for both IV alteplase and EVT should receive IV alteplase first without delay—do not wait for vascular imaging if clinical criteria for thrombolysis are met. 1, 6

Mechanical thrombectomy can be performed up to 6 hours (or longer with advanced imaging selection) and should be considered as an alternative when IV thrombolysis is contraindicated. 6, 3

System Requirements

Treatment should occur within a coordinated system including rapid neurovascular imaging, coordination between EMS and stroke teams, local neurointervention expertise, and access to stroke unit care. 1