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Pharmacy & Acute Care University
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Emergency Medicine Neurology 211

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  1. Acute Ischemic Stroke Pharmacotherapy
    9 Topics
    |
    2 Quizzes
  2. Hemorrhagic Stroke
    9 Topics
    |
    3 Quizzes
  3. Status Epilepticus
    10 Topics
    |
    3 Quizzes
  4. Migraine and headaches
    10 Topics
    |
    3 Quizzes

Quizzes

Participants 396

  • Allison Clemens
  • April
  • ababaabhay
  • achoi2392
  • adhoward1
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Lesson Progress
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Treatment Goals

Time is brain! 

  • As a stroke progresses, human nervous tissue is rapidly and irreversibly lost. 
    1. For every minute an ischemic stroke is untreated, the average patient loses approximately 1.9 million neurons 
    2. Penumbra: a salvageable zone around the area of infarction 
    3. Goal

the goal of treatment and early intervention is to salvage as much brain tissue as possible to prevent further ischemia  

  • Time
    1. Symptom onset is <4.5 hours
      • To be a candidate for fibrinolytic treatment one must present within 4.5 hours of symptom onset
      • Symptom onset (time symptoms manifested) is NOT the time a patient is found with symptoms
    2. Patients who wake up with symptoms or have unclear time of onset (>4.5 hours last known well)
      • WAKE-UP trial
        1. Evaluated: patients who woke up with a stroke or those with unclear time of onset (4.5 of stroke recognition) 
        2. Imaging: MRI used to determine if there is a mismatch
          • Abnormal signal in diffusion weighted imaging (DWI) and no visible signal change on fluid attenuated inversion recovery (FLAIR)
        3. Outcome: Treatment with alteplase improved functional outcome and did not increase the risk of death or major bleed
    3. Symptom onset within 6-24 hours
      • May be a candidate for mechanical thrombectomy 
    4. Door to needle time
      • Within 60 minutes

Fibrinolytic Therapy

Mechanism of action

  1. Binds to fibrin
  2. Activates fibrin bound plasminogen 
  3. Converts plasminogen to plasmin 
  4. Plasmin breaks down fibrin, dissolving the clot 

Exclusion criteria 

  1. Fibrinolytic medications are high risk medications. Clinicians must cautiously and thoroughly evaluate patients to determine if they are eligible for treatment. 
  2. Blood glucose (BG)
  • Prior to consideration a BG MUST be obtained. Hypoglycemia may mimic symptoms of stroke. This is easily attainable and when corrected may lead to symptom resolution.
    • The American Diabetes Association define hypoglycemia as a BG <70 mg/dL 
  • The AIS guidelines recommend the following
    • BG >50 mg/dL 
      • IV thrombolytic therapy recommended if initial BG is >50 mg/dL
    • BG <60 mg/dL (hypoglycemia)
      • Treat with dextrose 

3. Blood pressure (BP) 

  • Blood pressure should be cautiously lowered in patients with elevated BP who are otherwise eligible for fibrinolytic therapy
  • Goal blood pressure prior to fibrinolytic therapy
    • <185/110 mmHg
  • If BP is not within targeted range (<185/110 mmHg) may consider the following pharmacologic treatments to assist with BP control  
  1. Labetalol IV push 
    • Dose: 10-20 mg IV over 1-2 minutes 
    • May repeat once 
  2. Nicardipine IV infusion 
    • Initial rate: 5 mg/hr 
    • Titrate up by 2.5mg/hr every 5-15 minutes 
    • Maximum rate: 15 mg/hr
  3. Clevidipine IV Infusion 
    • Initial rate: 1-2 mg /hr 
    • Titrate by doubling the dose every 2-5 minutes until desired BP achieved 
    • Maximum rate: 21 mg/hr

Contraindications to fibrinolytic therapy 

  1. Hypoglycemia (section 2ii)
    • BG <50 mg/dL
    • Treat hypoglycemia prior to fibrinolytic therapy 
  2. Hypertension (section 2iii)
    • BP >185/110 mmHg
  3. NIHSS 0-5 (mild non-disabling stroke) 
  4. In the last 3 months has had:
    • An ischemic stroke 
    • Severe head trauma 
    • Intracranial/intraspinal surgery 
  5. Current or history of intracranial hemorrhage 
  6. GI malignancy or bleed in the last 21 days 
  7. Coagulopathy
    • Platelets <100/mm3
    • INR >1.7
    • aPTT >40 s
    • PT >15 s

8. Infective endocarditis 

9. Aortic arch dissection 

10. Use of glycoprotein iib/iiia receptor inhibitors

  • Abciximab (ReoPro®)
  • Tirofiban (Aggrastat®)
  • Eptifibatide (Integrilin®)

11. Treatment dose of low molecular weight heparin (LMWH) in the last 24 hours 

12. Thrombin inhibitors or Factor Xa inhibitors 

  • Unless lab tests (aPTT, INR, platelet count, thrombin time, factor Xa assay, etc.) are within normal limits OR patient has not received a dose in >48 hours 

Thrombolytic therapy 

  1. Alteplase (Activase®)
    • Mechanism (section 4-b-i)
    • Dose
      • 0.9 mg/kg (maximum 90 mg) over 60 min
      • Bolus: 10% of total dose over 1 min
      • Continuous infusion: Remainder 90% of dose over 60 min
  2. Tenecteplase (TNKase®)
    • Mechanism
      • Modified recombinant tissue type plasminogen activator 
    • Dose (off-label for AIS)
      • 0.25 mg/kg IV push 
      • Max dose: 25 mg 
    • Hypothetical advantages of Tenecteplase over alteplase
      • Greater fibrin specificity 
      • Longer half life 
      • Ease of administration (IV push rather than continuous infusion) 
  3. Blood pressure parameters
    • During and after fibrinolytic treatment blood pressure of <180/105 mmHg must be maintained 
  4. Adverse events
    • Intracranial bleeding <24 hours post administration of thrombolytic treatment
      • Manifestation/symptoms
        • Development of severe headache, acute HTN, N/V, or worsening neurologic exam
      • Management
        • Stop alteplase infusion (if running) 
        • Order labs
          • CBC, PT(INR), aPTT, fibrinogen, and type and cross-match
        • Obtain an emergent head CT 
      • Treatment (if confirmed on imaging)
        • Cryoprecipitate 10 units
          • Infuse over 10-30 minutes 
          • If fibrinogen <200 mg/dL administer an additional dose (10 units) 
        • Tranexamic acid or aminocaproic acid
          • Tranexamic acid 1,000 mg
            • Infuse over 10 min 
          • Aminocaproic acid 4–5 g
            • Infuse over 1 hour 
            • followed by 1,000 mg IV until bleeding is controlled
        • Supportive care
      • Follow up
        • Hematology and neurosurgery consult 
    • Orolingual angioedema 
      • Manifestation/symptoms
        • Edema that may involve the following regions
          • The anterior tongue and lips
          • Larynx, palate, floor of mouth or oropharynx 
      • Management
        • Maintain/protect airway
          • If symptoms manifest quickly (within 30 minutes)- higher risk of intubation  
        • Stop alteplase infusion (if running) and hold ACE-inhibitors
      • Treatment
        • Administer the following IV formulations
          1. Methylprednisolone 125 mg 
          2. Diphenhydramine 50 mg 
          3. Ranitidine 50 mg OR famotidine 20 mg 
        • If angioedema continues to worsen administer the following
          • Epinephrine (0.1%) 0.3 mL IM
        • If angioedema continues despite the above treatment methods may consider the following
          • Icatibant (bradykinin B2 receptor antagonist) 30 mg subcutaneously 
        • Supportive care

Disposition/Monitoring

  1. Intensive Care Unit (ICU) or Stroke Unit admission
  2. Strict blood pressure monitoring 
    • Goal BP <180/105 mmHg 
      • Must be maintained during infusion and 24 hours after administration 
    • BP monitoring is as followed
      • Every 15 minutes for 2 hours (from start of fibrinolytic therapy) then
      • Every 30 minutes for 6 hours then 
      • Every hour for 16 hours 
  3. Obtain follow up CT or MRI 24 hours after fibrinolytic treatment prior to initiating anticoagulation/antiplatelet agents