What is the recommended treatment protocol for patients with acute ischemic stroke receiving intravenous thrombolysis with alteplase (tissue plasminogen activator, tPA)?

Recommended Treatment Protocol for Acute Ischemic Stroke with Intravenous Thrombolysis

All eligible patients with acute ischemic stroke should receive intravenous alteplase 0.9 mg/kg (maximum 90 mg) as rapidly as possible after CT scan excludes hemorrhage, with 10% given as a bolus over 1 minute and 90% infused over 60 minutes. 1, 2

Time-Based Treatment Algorithm

0-3 Hour Window (Strongest Evidence)

• Administer IV alteplase immediately to all patients meeting NINDS criteria 1, 2
• This represents Class I, Level A evidence with the most robust data for improved functional outcomes 1, 2
• Target door-to-needle time <60 minutes in 90% of patients, with optimal median of 30 minutes 1, 2
• Earlier treatment within this window provides greater benefit—every minute counts 3, 4

3-4.5 Hour Window (Extended Window)

• Administer IV alteplase using identical dosing protocol but apply additional exclusion criteria 1, 3
• This represents Class I, Level B evidence based on ECASS III trial 1, 3
• Additional exclusions for 3-4.5 hour window:
  • Age >80 years 1, 2
  • Any oral anticoagulant use regardless of INR 1, 5
  • NIHSS score >25 1, 5
  • Combined history of both diabetes and prior stroke 1, 2

Beyond 4.5 Hours

• Do not administer standard IV alteplase beyond 4.5 hours 1, 2
• Consider advanced imaging (perfusion CT or MRI) to identify candidates for mechanical thrombectomy 1

Precise Dosing Protocol

Critical dosing details (this differs from MI protocol): 1, 2, 5

• Total dose: 0.9 mg/kg body weight (absolute maximum 90 mg) 1, 5
• Initial bolus: 10% of total dose (0.09 mg/kg) administered IV push over exactly 1 minute 1, 2, 5
• Continuous infusion: Remaining 90% (0.81 mg/kg) infused over 60 minutes 1, 2, 5

Common pitfall: Never use the myocardial infarction dosing protocol for stroke—this is a critical and potentially harmful error 1, 5

Pre-Treatment Requirements

Imaging

• Brain CT or MRI must be performed immediately to exclude hemorrhage 1, 2
• If uncertainty exists regarding CT interpretation, consult radiology urgently 1
• Do not delay treatment for advanced imaging if patient meets clinical criteria 1

Laboratory Testing

• Only blood glucose must be checked before administering alteplase 1, 2, 5
• Treat hypoglycemia (glucose <60 mg/dL or 3.3 mmol/L) with IV dextrose before thrombolysis 1
• Other labs (CBC, electrolytes, creatinine, INR, PTT, troponin) should be obtained but must not delay treatment 1, 2

Blood Pressure Management

• BP must be lowered below 185/110 mmHg before initiating alteplase 1, 2, 5
• Treat hypertension emergently to meet this threshold 1, 5
• Exception: Emergency treatment of hypertension is indicated if concomitant acute MI, aortic dissection, or preeclampsia/eclampsia exists 1

Post-Administration Management

Immediate Monitoring

• Hold all antiplatelet agents for 24 hours post-alteplase 2
• Monitor neurological status closely for deterioration 1
• Maintain oxygen saturation ≥94% 1
• Correct hypotension and hypovolemia to maintain organ perfusion 1

24-Hour Protocol

• Perform CT scan at 24 hours post-thrombolysis to exclude hemorrhage 2
• Only after hemorrhage is excluded, initiate aspirin 160-325 mg 2
• Do not use therapeutic parenteral anticoagulation in the acute phase 2

Complication Management

• For angioedema: Use staged response with antihistamines, glucocorticoids, and standard airway management per local protocol 1
• For bleeding complications: There is insufficient evidence to routinely use cryoprecipitate, fresh frozen plasma, prothrombin complex concentrates, tranexamic acid, factor VIIa, or platelet transfusions 1
• Decisions regarding reversal agents should be individualized based on severity 1

Special Populations and Considerations

Patients on Direct Oral Anticoagulants (DOACs)

• Do not routinely administer alteplase to patients on DOACs 1, 5
• In comprehensive stroke centers with DOAC level testing and reversal agents, thrombolysis may be considered after consultation with hematology 1
• Consider mechanical thrombectomy as alternative for eligible patients 1

Mechanical Thrombectomy Candidates

• Administer IV alteplase even if mechanical thrombectomy is planned 1, 2
• Do not wait to evaluate response to alteplase before proceeding to thrombectomy 1, 5
• Patients with large vessel occlusion should receive both therapies when eligible 1

Uncertain Clinical Scenarios

• When uncertainty exists about treatment eligibility, urgently consult stroke specialist within institution or via telestroke 1
• This applies to pediatric stroke, pregnant women, and patients with atypical presentations 1

Patients with Prior Cerebral Hemorrhage

• History of cerebral hemorrhage is not an absolute contraindication 6
• Symptomatic ICH rates are higher (8.3% vs 4.3%) but functional outcomes may still benefit from treatment 6
• Requires careful risk-benefit discussion and stroke specialist consultation 1, 6

Alternative Agent: Tenecteplase

Tenecteplase may be considered as an alternative to alteplase in select patients (Class IIb, Level B-R) 2, 7

• Dosing: Single IV bolus based on weight: 30 mg for <60 kg, 35 mg for 60-69 kg 2, 7
• Advantages: Single bolus administration versus 60-minute infusion, longer half-life 7
• Current evidence: Noninferior to alteplase for excellent functional outcomes, superior recanalization rates before thrombectomy 7
• Limitation: Less established than alteplase; best reserved for patients with minor neurological impairment and no major intracranial occlusion 2, 7

Critical Safety Data

Number needed to treat for favorable outcome: 8-14 patients 2

Number needed to harm for symptomatic ICH: 17 patients 2

Symptomatic ICH rates:

• 0-3 hours: Increased risk but outweighed by benefit 1, 8
• 3-4.5 hours: 2.4% with alteplase vs 0.2% with placebo 3
• Overall mortality not significantly increased with treatment 3, 4

System-Level Requirements

The effectiveness of alteplase is best established in institutions with:

• Organized stroke protocols and rapid response teams 1
• 24/7 access to CT imaging and interpretation 1
• Stroke specialist availability on-site or via telestroke 1
• Standardized monitoring and complication management protocols 1

Common pitfall: Institutions without these systems in place have less established safety and efficacy data 1