AIS

TNK Eligibility

• 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).

ID-IMR

ID-IMR— (PI: Aziz)

LVO Required

ICA/M1/M2 (any)

LKW

24 hrs

Pre-stroke mRS

—

NIHSS

—

ASPECTS

—

MRI Capability

Must be able to undergo MRI

ICT/AC

—

MT Required

Yes

MT Device

—

Final mTICI

2c-3

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SISTER

SISTER — (Stite PI: Aziz)

LVO Required

1. LVO not required
2. Anterior circ perfusion mismatch

LKW

4.5 – 24 hrs

Pre-stroke mRS

0 - 2

NIHSS

≥4

ASPECTS

>6 (>7 if MRI)

MRI Capability

—

ICT/AC

No Thrombolytics (IV/IA)

MT Required

No

MT Device

—

Final mTICI

—

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STEP DOMAIN A (Low NIHSS)

STEP-Domain A (Low NIHSS) — (PI: Demel)

LVO Required

ICA or M1 MCA

LKW

24 hrs

Pre-stroke mRS

0-2

NIHSS

0-5

ASPECTS

>6 (>7 if MRI)

MRI Capability

—

ICT/AC

—

MT Required

—

MT Device

—

Final mTICI

—

ORDER to USE: XXXXXXX

AFTER HOURS CALL: XXXXXXX

ACTIVE SITES: XXXXXXX

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• What is the best way to start investing?

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Acute Ischemic Stroke - LYTICS

Thrombolytic Treatment

• TNK Eligibility
  • 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).
• TNK Criteria (2018 AHA/ASA Guidelines)
  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
• Goal Times (GWTG)
  • 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 
• TNK Dosing
  • Mix IV thrombolytic (rt-PA)
  • Recommended Dosage for Acute Ischemic Stroke (AIS)
    • Initiate treatment as soon as possible and within 3 hours after the onset of stroke symptoms.
    • TNKase is for IV administration only, administered as a single bolus over 5 seconds.
    • Maximum recommended dose is 25 mg (5 mL). Increased Risk of Heart Failure and Recurrent Ischemia when used with recommended dose is 25 mg (5 mL).
    • Administer as bolus over 5 seconds, followed by a 10mL bolus of 0.9% sodium chloride (NS).
    • Individualize dosage based on the patient’s weight (see Table 1 below).
• Adjunctive / Additional therapies
  • 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 NICU Transfer
  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.
• Post-IV thrombolytic stroke monitoring
  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.
• BP management considerations: PRE-TREATMENT
  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
• BP management considerations: POST-TREATMENT
  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
• Management of sICH after thrombolysis
  • 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.
• Management of angioedema after thrombolysis
  • If angioedema is suspected, the treating stroke physician (513-584-8282) should be contacted IMMEDIATELY.
  •  
  • 

Acute Ischemic Stroke (2023)

Thrombolytic Treatment - AIS

• TNK Eligibility
  • 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).
• TNK Criteria (2018 AHA/ASA Guidelines)
  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
• Goal Times (GWTG)
  • 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 
• TNK Dosing
  • 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.
• Adjunctive / Additional therapies
  • 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 NICU Transfer
  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.
• Post-IV thrombolytic stroke monitoring
  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.
• BP management considerations: PRE-TREATMENT
  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
• BP management considerations: POST-TREATMENT
  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
• Management of sICH after thrombolysis
  • 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.
• Management of angioedema after thrombolysis
  • If angioedema is suspected, the treating stroke physician (513-584-8282) should be contacted IMMEDIATELY.
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