Acute Ischemic Stroke

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Thrombolytic Treatment - AIS

    • Patients of any age with suspected ischemic stroke within 4.5 hours of last known well.
    • Selected patients beyond 4.5 hours from last known well, with unwitnessed time of onset.
    • See more details regarding eligibility criteria below (GWTG Goal Times).
  • Within 4.5 hrs:
    • No upper age limit
    • SBP <185 or DBP <110 (see pretreatment recommendations below)
    Exclusions:
    • CT brain imaging exhibits extensive regions of clear hypoattenuation
    • Ischemic stroke within 3 months
    • Severe head trauma within 3 months
    • Intracranial/intraspinal surgery within 3 months
    • History of intracranial hemorrhage
    • Suspected subarachnoid hemorrhage
    • GI malignancy or recent GI bleed
    • Platelets <100 000/mm3, INR >1.7, aPTT >40 s, or PT >15 s
    • LMWH within 24 hours
    • DOAC within 48 hours
    • High suspicion of infectious endocarditis
    • Suspected aortic dissection
    • Suspected intra-axial intracranial neoplasm
    Beyond 4.5 hours from last known well (based on published WAKE UP trial: https://www.nejm.org/doi/full/10.1056/NEJMoa1804355)
    • Unwitnessed event (recognized symptoms upon awakening or unable to report timing of onset due to, for example, confusion or aphasia)
    • MRI suggestive of more recent onset of event (Based on MRI-DWI positivity and FLAIR negativity
    • Note that acute MRI may be challenging to obtain in some practice environments and this may limit eligibility by this criteria.
    • Age up to 80 years and functionally independent
    • No LVO; LVO patients are prioritized for EVT
    • Not severe stroke (NIHSS <=25)
    • Meets other standard IV thrombolytic eligibility other than time from last known well
    • Determine “Last Known Well” time. WITHIN 5 MIN OF ED ARRIVAL
    • Activate Stroke Team (513-584-8282) WITHIN 10 MIN OF ED ARRIVAL
    • Perform non-contrast CT scan and CTA (head/neck). WITHIN 20 MIN OF ED ARRIVAL
    • Draw bloods for lab tests (CBC, renal, coags, pregnancy, fingerstick glucose).
    • Obtain fingerstick glucose promptly to determine IV thrombolytic eligibility.
    • Do not delay thrombolytic for other lab results unless clinical suspicion of abnormality.
    • Establish two IV lines.
    • Record blood pressure.
    • Gently treat (usually labetalol 10 mg to start, assuming no clinical contraindications) if ≥185 systolic or ≥110 diastolic if potential IV thrombolytic candidate (details below).
    • Review eligibility criteria for IV thrombolytic (details below)
    • Interpret CT scan -- rule out bleed or subacute ischemia. WITHIN 35 MIN OF ARRIVAL
    • Start IV thrombolytic bolus if eligible. WITHIN 45 MIN OF ARRIVAL 
    • Tenecteplase (TNKase) - 0.25mg/kg (maximum 25mg). Administer as a bolus over 5 seconds, followed by a 10mL bolus of 0.9% sodium chloride (NS).
    • OR, if tenecteplase is not available, use alteplase (Activase) - 0.9 mg/kg dose (maximum 90 mg). Administer 10% as bolus over 1-2 minutes and the remainder as an infusion over 60 minutes.
    • Do not use the cardiac dose.
    • Do not exceed the maximum dose.
    • Use rt-PA = tenecteplase = TNKase. Do not use other thrombolytic agents. Use alteplase (Activase) only if tenecteplase is unavailable in the adult population. Note that the dose is different for each IV thrombolytic (see above).
    • Do not give aspirin, clopidogrel, heparin, warfarin or other oral anticoagulants for the first 24 hours after IV rt-PA.
    • Potential IV thrombolytic candidates should not receive antiplatelets (aspirin, clopidogrel) or anticoagulants (heparin, warfarin, or DOACs) upon arrival to ED.
    • However, patients who have taken antiplatelets prior to arrival in the Emergency Department are still considered IV thrombolytic candidates and those taking anticoagulant medications may still be candidates as well.
    • At 24 +/- 6 hours, a non-contrast CT scan or MRI should be performed (to rule out any intracranial hemorrhage) before starting an antiplatelet or anticoagulant medication.
  • Consider transfer to a Neuroscience Intensive Care Unit for patients needing specialized monitoring and management including:
    • Severe (NIHSS ≥10) stroke with risk of malignant MCA syndrome requiring anticipation and consideration of decompressive hemicraniectomy by neurosurgery
    • Cerebellar stroke with risk of malignant edema requiring anticipation and consideration of posterior decompression by neurosurgery
    • Fluctuating neurological symptoms requiring specialized blood pressure management.
      Hold infusion and repeat head CT stat
    • Large vessel occlusion that may require endovascular measures in upcoming hours, given the higher risk of neurological deterioration.
  • Admit patient to ICU and follow post-IV thrombolytic order set, including:
    • Monitor BP and neuro status:
      Q15 min X 2 hours, q30 min X 6 hours, then q1 hour X 16 hours
    • Treat SBP≥180 or DBP ≥105 (details below)
    • Call stroke physician at 513-584-8282 if there is a decline in neuro status, new headache, nausea, or vomiting.
      Hold infusion and repeat head CT stat
    • NPO until swallowing assessed
    • DVT prophylaxis with intermittent stocking compression devices (SCDs) but no anticoagulants
    Consider transfer to a Neuroscience Intensive Care Unit for patients needing specialized monitoring and management including:
    • Severe (NIHSS ≥10) stroke with risk of malignant MCA syndrome requiring anticipation and consideration of decompressive hemicraniectomy by neurosurgery
    • Cerebellar stroke with risk of malignant edema requiring anticipation and consideration of posterior decompression by neurosurgery
    • Fluctuating neurological symptoms requiring specialized blood pressure management.
      Hold infusion and repeat head CT stat
    • Large vessel occlusion that may require endovascular measures in upcoming hours, given the higher risk of neurological deterioration.
  • For IV thrombolytic candidates: BP should be brought to SBP <185 mmHg or DBP <110 mmHg if possible. This must be done without aggressive antihypertensive treatment for the patient to remain eligible for IV thrombolytic. If blood pressure remains ≥185 systolic or ≥110 diastolic with nonaggressive measures (rarely), then the patient is not eligible for IV thrombolytic.
    • BP MANAGEMENT PRIOR TO IV THROMBOLYTIC ADMINISTRATION
      • Up to two of the following agents may be used for nonaggressive treatment:
        • Labetalol 10 to 20 mg IV over 1-2 minutes, may repeat X 1 (max dose 40 mg)
        • Nicardipine infusion, 5 mg/h, titrate up by 2.5 mg/h at 5-15-minute intervals (up to max dose 15 mg/h; when desired BP attained, reduce to 3 mg/h)
        • Enalaprilat 0.625 to 1.25 mg IV (up to max dose of 1.25 mg)
        • Hydralazine 10 mg IV over 1-2 minutes, may repeat X1 (max dose 20 mg)
        • Nitropaste 1 to 2 inches (up to max dose of 2 inches)
    • If IV thrombolytic not planned, then permissive HTN up to 220/120 may be reasonable
  • During/after treatment with thrombolytic or other acute reperfusion intervention, BP must be aggressively maintained at SBP <180 or DBP <105 BP should be brought to SBP <185 mmHg or DBP <110 mmHg if possible. This must be done without aggressive antihypertensive treatment for the patient to remain eligible for IV thrombolytic. If blood pressure remains ≥185 systolic or ≥110 diastolic with nonaggressive measures (rarely), then the patient is not eligible for IV thrombolytic.
    • Monitor BP every 15 minutes for first 2 hours, then every 30 minutes for next 6 hours, then every hour for the next 16 hours.
    • Monitor blood pressure every 15 minutes during the antihypertensive therapy. Observe for hypotension.

      BLOOD PRESSURE MANAGEMENT DURING/AFTER ADMINISTERING IV thrombolytic
      If systolic BP ≥180–230 mm Hg or diastolic BP ≥105–120 mm Hg:
      • Labetalol 10 mg IV followed by continuous IV infusion 2–8 mg/min; or
      • Nicardipine 5 mg/h IV, titrate up to desired effect by 2.5 mg/h every 5–15 minutes, maximum 15 mg/h
      If BP not controlled or diastolic BP >140 mm Hg:
      • Consider IV sodium nitroprusside
    • If an sICH is suspected, the treating stroke physician (513-584-8282) should be contacted IMMEDIATELY.
    • Suspect sICH if there is any acute neurological deterioration (new headache, acute hypertension, seizure, or nausea and vomiting) or acute increase in BP.
    • If hemorrhage is suspected, then do the following:



      Management of sICH after thrombolysis is the same with tenecteplase as it is with alteplase.
    • If angioedema is suspected, the treating stroke physician (513-584-8282) should be contacted IMMEDIATELY.
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