thrombolysis for ischemic stroke

Epidemiology

• underutilized
• administered to only 1.12% of ischemic stroke hospitalizations 1999-2004

Indications

• ischemic stroke with onset within 3 hours
  • the window may be extended to 4.5 hours, unless:
    • taking oral anticoagulants (warfarin)
    • NIH stroke scale score > 25
    • history of both stroke & diabetes
  • age > 80 years not a limitation for r-tPA within 4.5 hours
    • increased risk of intracranial hemorrhage & mortality offset by lower disability from tPA when administered 3-6 hours after symptom onset)
  • no benefit of alteplase if given > 4.5 hours after stroke
  • hypoperfused but salvageable brain regions on perfusion imaging may benefit from alteplase thrombolysis for up to 9 hours
• neurological deficit measurable deficit on NIH Stroke scale
  • > minimal weakness, isolated ataxia, isolated sensory loss or isolated dysarthria
  • benefit for patients with mild stroke (NIH Stroke scale 0-4)
• may be benficial for sickle cell patients with ischemic stroke

Contraindications

• historical
  • stroke or serious head trauma within the last 6 months
  • major surgery or serious trauma within the past 14 days
    • this may be relative contraindication
  • history of intra-cranial hemorrhage, AV malformation or aneurysm
  • GI or urinary tract hemorrhage within the previous 21 days
  • arterial puncture at a non-compressible site within the previous 7 days
  • lumbar puncture within the previous 7 days
  • recent myocardial infarction-induced pericarditis
    • recent myocardial infarction seems not a contraindication
  • patient on anticoagulation therapy
    • direct oral anticoagulant (DOAC) within the past 48 hours
      • insufficient evidence of excess harm
• clinical
  • rapidly improving neurologic signs
  • minor symptoms, mild, nondisabling stroke symptoms
  • systolic blood pressure (BP) > 185 mm Hg
  • diastolic BP > 110 mm Hg
  • mean arterial pressure > 130 mm Hg
  • aggressive BP management needed to control BP
  • seizure at onset of stroke
  • symptoms suggestive of subarachnoid hemorrhage
• laboratory
  • PT > 15 seconds, INR > 1.7
    • some patients on warfarin (INR < 1.8) may safely receive r-tPA following ischemic stroke
  • elevation of PTT in a patient who has received heparin within 48 hours of stroke onset
  • platelet count < 100,000/mm3
  • serum glucose < 50 mg/dL or > 400 mg/dL
  • women of child-bearing age with a positive pregnancy test
• patient & family do not understand potential benefits & risks
• age > 80 years
• diabetes mellitus with prior stroke (MKSAP19)
  • prior ischemic stroke & diabetes appear not to be contraindications

Benefit/risk

• of no benefit
  • 12 trials of which 2 found benefit & 4 found harm

* shorter door-to-needle times for administering tissue plasminogen activator (tPA) associated with lower mortality hospital readmissions at 1 year

Procedure

Administration:

• tissue plasminogen activator (tPA) 0.9 mg/kg, max 90 mg
• administer 10% of tPA as a bolus
• administer remaining 90% of tPA as an infusion over 1 hour
• ultrasound applied to lesion may enhance recanalization
• IV altepase
• tenecteplase may be reasonable alternative to alteplase if eligible for arterial thrombectomy
• argatroban of no benefit added to alteplase

Precautions:

• do not give anticoagulants for 24 hours from start of tPA administration
• do not give antiplatelet agents for 24 hours from start of tPA administration
• admit to intensive care unit or acute stroke unit
• maintain systolic BP < 180 mm Hg & diastolic BP < 105 mm Hg
• delay central venous line placement or arterial puncture for 24 hours
• delay inserting indwelling bladder (foley) catheter for > 30 minutes after tPA administration
• delay nasogastric (NG) tube placement for 24 hours

Radiology

• head CT scan without contrast
  • no evidence of intracranial hemorrhage
  • no early signs of major hemispheric infarct
    • edema, mass effect, sulcal effacement
    • if present re-evaluate time of onset 3 presence of these signs may be associated
  • no evidence of prior stroke
  • thrombolysis may not benefit small CT perfusion deficits
• repeat head CT scan without contrast during or after procedure if patient's neurologic condition deteriorates to rule out intracerebral hemorrhage
• MRI to select acute stroke patients for thrombolysis
  • to identify diffusion-positive, FLAIR-negative lesions eligible patients who awakened from sleep with stroke symptoms or otherwise have unclear time of onset
  • may lead to favorable outcome but could increase risk

Complications

• symptomatic intracerebral hemorrhage
  • 6.4% of treated patients
    • mortality is ~50%
  • incidence may be slightly higher in patients > 80 years of age
  • if tPA-induced intracerebral hemorrhage suspected
    • stop infusion, evaluate with another head CT
• alteplase associated with higher mortality in 1st week after ischemic stroke, but lower mortality thereafter

Management

• Blood pressure (BP) management:
  • monitor BP for 24 hours after starting tPA administration
    • every 15 min for 2 hours
    • every 30 min for 6 hours
    • hourly for remaining 16 hours
    • blood pressure should be maintained below 180 mm Hg systolic & 105 mm Hg diastolic for at least the 1st 24 hours post thrombolysis
  • when an acute rise in blood pressure is observed
    • consider intracerebral hemorrhage
    • stop tPA infusion
    • obtain head CT
  • systolic BP 180-230 or diastolic BP 105-120 (rechecked)
    • labetolol 10 mg IV, over 1-2 min
    • nicardipine IV is an alternative
    • monitor every 10 min
    • repeat 10-20 mg IV every 10-20 min PRN up to 150 mg
    • avoid hypotension
  • systolic BP > 230 mm Hg or diastolic BP 121-140 mm Hg
    • labetolol 10 mg IV, over 1-2 min q 10 min up to 150 mg
    • nicardipine IV is an alternative
    • if response in inadequate, use sodium nitroprusside
  • diastolic BP > 140 mm Hg
    • nitroprusside 0.5-10 ug/kg/min
    • monitor closely
      • nitroprusside effective for malignant hypertension, but may increase intracranial pressure
    • avoid hypotension
• Post procedure:
  • CT angiography to determine eligibility for arterial thrombectomy
  • aspirin or clopidogrel 24 hours after thrombolysis

Notes

• tPA is apparently safe if used in patients with stroke mimetic
• outcomes generally better in younger patients
• outcomes better with earlier thrombolysis
  • each minute saved between stroke onset & tPA translates to ~ 2 days of disability-free life
  • number of patients needed to treat = 4.5 when thrombolysis is given within 1.5 hours of stroke onset
  • number of patients needed to treat = 18 when given 3-4.5 hours after stroke onset
• mobile stroke units afford shorter 'time-to-thrombolysis' -impact on outcomes variable, possibly trending toward improved outcomes
• improves quality of life & functional capacity up to 18 months after ischemic stroke
• benefit for minor stroke unclear

More general terms

• thrombolytic therapy

Additional terms

• ischemic stroke
• mobile stroke unit; STroke Emergency MObile (STEMO)