Thrombolytics for acute ischemic stroke

Background

1. NINDS Trial (pts treated within 3hrs)
   1. Benefits:
      1. 12% absolute risk reduction benefit (NNT = 8-9) at 3 months
         1. Lower percentage of pts who left hospital severely disabled
      2. Comparable 3-month mortality rate (even with increased rate of ICH)
   2. Risks:
      1. Intracranial hemorrhage occurs in 6.4% of treated pts
2. ECASS Trial (pts treated within 4.5hrs)
   1. Confirmed NINDS findings even when therapeutic window extended to 4.5hr
   2. As a result AHA/ASA now recommends tPA for pts presenting up to 4.5hr after sx onset

Studies Required

1. Head CT
2. CBC
3. Coags
4. Glu check
5. ECG
6. Urine pregnancy (pregnancy is relative contraindication)

tPA <3hr

Inclusion Criteria

1. Diagnosis of ischemic stroke causing measurable neuro deficit
2. Clear onset (last witnessed well) <3hr (see below for extension to <4.5hr)
3. Age >18yr

Exclusion Criteria

(Only need to wait for plt, INR, PTT if there is clinical suspicion of abnormal value, pt has received heparin or warfarin, or use of anticoagulants is unknown)

1. Historical
   1. Stroke or head trauma in previous 3 months
   2. Any history of intracranial hemorrhage
   3. Major surgery in the previous 14 days
   4. GI or urinary tract bleeding in previous 21 days
   5. MI in previous 3 months
   6. Arterial puncture at noncompressible site in previous 7 days
2. Clinical
   1. Spontaneously clearing stroke symptoms
   2. Only minor and isolated neurologic signs
   3. Seizure at onset of stroke if residual impairments are due to postictal phenomenon; #Symptoms of stroke suggestive of SAH
3. Persistent SBP >185 or DBP >110 despite treatment
4. Active bleeding or acute trauma (fracture) on exam
5. Labs
   1. Platelets <100K
   2. Serum glucose <50
   3. INR >1.7 if on warfarin
   4. Elevated PTT if on heparin
   5. Use of dabigatran within 48hrs is relative contraindication
6. Head CT
   1. Evidence of hemorrhage
   2. Evidence of multilobar infarction w/ hypodensity involving >33% of cerebral hemisphere

tPA between 3-4.5hrs

Inclusion Criteria

1. Same as for <3hr

Exclusion Criteria

1. All of the above plus:
   1. Age >80yr
   2. Combination of both previous stroke and DM
   3. NIHSS score >25
   4. Oral anticoagulant use regardless of INR

Administration

1. Alteplase 0.9mg/kg IV (max 90mg total)
   1. 10% of dose is administered as bolus; rest is given over 60min
2. Neuo check Q15min x 2hr
3. No anticoatulation/antiplatelets x 24hr
4. Blood pressure
   1. Keep SBP <180, DBP <105
   2. If SBP is 180-230 or DBP is 105-120:
      1. Labetalol 10mg IV over 1–2 min; repeat dose q10–20min up to 300mg max OR
      2. Labetalol 10mg IV followed by infusion at 2–8 mg/min
   3. If SBP is >230 or DBP 121-140:
      1. Labetalol as above OR
      2. Nicardipine 5mg/hr; titrate up by 2.5 mg/hr at 5-15min intervals; max dose 15mg/hr
   4. If BP not controlled by above measures:
      1. Nitroprusside 0.5–10mcg/kg/min
         1. Continuous arterial monitoring advised
         2. Use w/ caution in pts with hepatic or renal insufficiency

tPA Complications

• Post-tPA Hemorrhage
• Angioedema

See Also

• CVA (Main)
• CVA (Post-tPA Hemorrhage)

Source

• Tintinalli
• Hacke W, Kaste M, Bluhmi E, et al: Thrombolysis with alteplase 3 to 4.5 h after acute ischemic stroke. N Engl J Med 359(13): 1317, 2008
• ACEP/AAN Guidelines
• AHA/ASA Guidelines