The latest article in our Clinical Therapeutics series, Intravenous Thrombolytic Therapy for Acute Ischemic Stroke, comes from Dr. Lawrence Wechsler at the University of Pittsburgh Medical School. An 81-year-old man presents to the ER with an acute ischemic stroke; IV thrombolytic therapy is recommended. Administered as a therapeutic agent within 4.5 hours after stroke, tissue plasminogen activator has been shown to improve neurologic outcomes.
Stroke is the leading cause of adult disability in the United States. Despite advances in stroke prevention and acute therapy, over 795,000 strokes occur per year in the U.S.
• How soon after a stroke does rt-PA need to be given for its use to increase the probability of a favorable outcome?
Within 3 hours of onset of stroke, intravenous rt-PA increases the probability of favorable outcome. Some stroke centers now treat patients 3 to 4.5 hours from stroke onset. However, at present only treatment within 3 hours is approved by the FDA.
• How should hypertension be managed when thrombolytic therapy for acute stroke is being considered?
Current guidelines recommend treatment of hypertension to achieve a systolic pressure less than or equal to 185 mm Hg systolic and diastolic values less than or equal to 110 mm Hg prior to administering intravenous rt-PA. One or two doses of labetalol may be used to bring the blood pressure under these limits, but if blood pressure does not decrease to that level quickly, intravenous nicardipine, or, more rarely, sodium nitroprusside may be started to titrate blood pressure rapidly to this level.
Table 1. Inclusion and Exclusion Criteria for Intravenous t-PA Therapy in Patients with Acute Ischemic Stroke.
Morning Report Questions
Q: Current guidelines suggest that thrombolytic therapy be withheld from which patients with acute ischemic stroke?
A: If a focal area of low density (or “hypodensity”) is seen on computed tomography of the brain that involves more than 1/3 of the middle cerebral artery territory, most treatment protocols recommend withholding thrombolytic therapy, because this finding (which suggests irreversible injury) is predictive of subsequent hemorrhagic transformation of the infarct in some studies. Platelet count should be greater than or equal to 100,000, prothrombin time <15 seconds (or INR <1.7) and glucose >50 mg/dl before rt-PA is administered.
Q: Which patients with acute stroke are at highest risk of developing a hemorrhage following treatment with rt-PA?
A: Symptomatic intracranial hemorrhage occurs in 1.7 to 8.0% of treated patients. In addition to age and NIH stroke scale score, other identified independent risk factors for symptomatic intracranial hemorrhage include CT hypodensity, elevated serum glucose and persistence of proximal arterial occlusion beyond 2 hours from rt-PA bolus.