What is the protocol for using Tissue Plasminogen Activator (tPA) (TNK) and pressors in acute ischemic stroke management?

TNK and Pressors in Acute Ischemic Stroke Management

Blood Pressure Management Before and During Thrombolytic Therapy

Blood pressure must be lowered to <185/110 mmHg before administering thrombolytic therapy, and aggressive treatment with continuous infusion agents like nicardipine is safe and does not increase hemorrhagic complications. 1

Pre-Treatment Blood Pressure Control

• Absolute requirement: Systolic BP must be <185 mmHg and diastolic BP <110 mmHg before initiating tPA or TNK 2, 3
• Severe uncontrolled hypertension (SBP >180 mmHg or DBP >110 mmHg unresponsive to therapy) is an absolute contraindication to thrombolytic therapy 2
• Patients requiring aggressive BP lowering with continuous nicardipine infusion before tPA have similar rates of symptomatic intracranial hemorrhage and functional outcomes compared to those not requiring treatment 1
• Do not exclude patients from thrombolytic therapy solely because they require aggressive BP management with pressors or continuous infusions 1

Post-Thrombolytic Blood Pressure Targets

After tPA/TNK administration, maintain systolic BP ≤180 mmHg and diastolic BP ≤105 mmHg for at least 24 hours. 4

• Monitor BP every 15 minutes for the first 2 hours 4
• Monitor BP every 30 minutes for hours 2-8 4
• Monitor BP hourly from hours 8-24 4
• If BP exceeds 180/105 mmHg, increase monitoring frequency and administer antihypertensive medications immediately 4

Thrombolytic Agent Selection and Dosing

Tenecteplase (TNK) 0.25 mg/kg (maximum 25 mg) as a single IV bolus is superior to alteplase for excellent functional outcomes and is the preferred agent when available. 5

TNK Dosing Protocol

• Single weight-based IV bolus: 0.25 mg/kg (maximum dose 25 mg) 6
• Administered over 5-10 seconds as a single bolus 6
• Significantly simpler workflow compared to alteplase, particularly advantageous for transfers or endovascular therapy 6
• TNK demonstrates superior rates of excellent functional outcome (mRS 0-1) at 3 months compared to alteplase (RR 1.05,95% CI 1.01-1.10) 5
• Similar safety profile to alteplase with no increased risk of symptomatic intracranial hemorrhage 5

Alteplase Dosing (if TNK unavailable)

• Total dose: 0.9 mg/kg (maximum 90 mg) 3
• Initial bolus: 10% of total dose IV over 1 minute 3
• Infusion: Remaining 90% infused over 60 minutes 3

Time Windows for Treatment

• <3 hours from onset: Strong recommendation for thrombolytic therapy (Level A evidence) 2, 3
• 3-4.5 hours from onset: Conditional recommendation for carefully selected patients (Level B evidence) 2, 3
• >4.5 hours: Contraindicated in routine practice 3
• Emerging evidence suggests TNK may be safe in selected patients with DWI-FLAIR mismatch up to 24 hours, but this remains investigational 7

Post-Thrombolytic Monitoring Protocol

All patients receiving thrombolytics must be admitted to an ICU or stroke unit for intensive monitoring for at least 24 hours. 4

Neurological Assessment Schedule

• Every 15 minutes during the infusion 4
• Every 30 minutes for 6 hours post-infusion 4
• Hourly from hours 6-24 4
• If severe headache, acute hypertension, nausea, vomiting, or neurological worsening occurs: immediately stop any remaining infusion and obtain emergent non-contrast CT 4

Critical Management Points

• Delay all invasive procedures for 24 hours: nasogastric tubes, indwelling bladder catheters, arterial lines 4
• Hold all anticoagulants and antiplatelet agents for 24 hours 4
• Obtain follow-up CT at 24 hours before initiating any antithrombotic therapy 4
• Symptomatic intracranial hemorrhage occurs in approximately 6% of patients (6.4% with alteplase, similar with TNK) 8, 5

Management of Hemorrhagic Transformation

If symptomatic ICH is suspected, immediately discontinue thrombolytic infusion, obtain emergent CT, and consider cryoprecipitate to restore fibrinogen. 4

• Symptomatic ICH rate: approximately 5-6% with proper patient selection 4, 8
• Emergency reversal measures include cryoprecipitate for fibrinogen replacement 4
• Consider neurosurgical consultation for large hemorrhages based on size, location, and clinical status 4

Critical Contraindications Related to Blood Pressure

Absolute Contraindications

• Severe uncontrolled hypertension unresponsive to emergency treatment (SBP >180 mmHg or DBP >110 mmHg) 2
• Any prior intracranial hemorrhage 2
• Ischemic stroke within 3 months (except acute ischemic stroke within 4.5 hours) 2

Relative Contraindications

• History of chronic, severe, poorly controlled hypertension 2
• Significant hypertension on presentation (SBP >180 mmHg or DBP >110 mmHg) that responds to treatment 2

Common Pitfalls to Avoid

• Failing to aggressively lower BP before thrombolysis: This is not a contraindication if BP responds to treatment 1
• Inadequate post-thrombolytic BP control: Failure to maintain strict BP targets increases hemorrhagic transformation risk 4
• Premature administration of antithrombotics: Wait 24 hours and obtain follow-up CT first 4
• Excluding patients who require nicardipine: Continuous infusion for BP control does not worsen outcomes 1
• Using alteplase when TNK is available: TNK offers superior functional outcomes with equivalent safety 5