Hyperacute Stroke Treatment: Inclusion and Exclusion Criteria

T-PA Benefit

• Odds ratio of favorable outcome if t-PA is given: – within 90 min of symptom onset= 2.81 (95% CI, 1.75-4.50) – Within 90 and 180 min of symptom onset= 1.55 (95% CI, 1.12-2.15) – Community registry study SITS-ISTR: frequency of favorable outcome is 56.3% (CI, 55.3-57%)

T-PA Benefit 3 to 4.5 hour

• Odds ratio of excellent outcome= 1.40 (95% CI, 1.05-1.85) • ECASS III trial odds ratio mRS 0-1: odds ratio 1.34 (95% CI, 1.02- 1.76)

T-pa Risk

• Major risk is intracerebral hemorrhage with variable rates of occurrence 1.9% to 10% • Risk of hemorrhage increases in proportion to degree to which the protocol is not followed • Angioedema estimated to occur between 1.3 – 5.1% – More associated with angiotensin converting enzyme inhibitor use – Infarct involving the insular and frontal cortex

Inclusion Criteria for Intravenous t-PA

• Diagnosis of ischemic stroke causing measurable neurological deficit • Onset of symptoms < 3hours before beginning treatment – Onset time is defined as either the witnessed onset of symptoms or the time last known normal if symptom onset was not witnessed • Aged > 18 years

Exclusion Criteria for Intravenous t-PA

• Significant head trauma or prior stroke in previous 3 months – Small stroke within 3 months may be considered but should be included in risk discussion with patient or family member • Symptoms suggest subarachnoid hemorrhage • Arterial puncture at a noncompressible site in previous 7 days

Exclusion Criteria for Intravenous t-PA

• History of previous intracerebral hemorrhage • Intracranial neoplasm, arteriovenous malformation, aneurysm • Recent intracranial or intraspinal surgery • Elevated blood pressure (systolic >185 or diastolic >110mm Hg)

Exclusion Criteria for Intravenous t-PA

• Active internal bleeding • Acute bleeding diathesis, including but not limited to: – Platelet count < 100,00/mm – Heparin received within 48 hours, resulting in abnormally elevated aPTT greater than the upper limit of normal – Current use of anticoagulant wit INR>1.7 or PT>15 seconds – Current use of direct thrombin inhibitors or direct factor Xa inhibitors with elevatd sensitive laboratory tests(i.e. aPTT, INR, ECT, TT, or appropriate factor Xa activity assays

Exclusion Criteria for Intravenous t-PA

• Blood glucose concentration <50 mg/dl – Can correct and reassess patient NIHSS • CT demonstrates multilobar infarction (hypodensity> 1/3 cerebral hemisphere

Relative Exclusion Criteria for Intravenous t-PA • Only minor or rapidly improving symptoms (clearing spontaneously) • Pregnancy • Seizure at onset with postictal residula neurological impairments • Major surgery or serious trauma within past 14 days • Recent gastrointestinal or urinary tract hemorrhage (within past 21 days) • Recent acute myocardial infarction (within previous 3 months)

Relative Exclusion Criteria for Intravenous t-PA

• Under some circumstances– with careful consideration and weighing of risk to benefit – patients may receive t-PA despite 1 or more relative contraindications.

Relative Exclusion Criteria for Intravenous t-PA

• Patients without recent use of oral anticoagulants or heparin, treatment with t-PA can be initiated before coagulation test results are back. Discontinue t-PA if exclusion criteria are met.

• Patients without a history of thrombocytopenia, treatment with t-PA can be initiated before platelet count is back. Discontinue t-PA if exclusion criteria are met.

Additional Inclusion Criteria for Intravenous t-PA use between 3 and 4.5 hours • Diagnosis of ischemic stroke causing a measurable neurological deficit • Symptom onset within 3 to 4.5 hours before beginning treatment

Additional Relative Exclusion For t-PA administration within 3 to 4.5 hours • Aged >80 years • Severe Stroke (NIHSS> 25) • Taking an oral anticoagulant regardless of INR • History of both diabetes and prior ischemic stroke

Warning Signs for Significant Hemorrhagic Transformation • Sudden onset of severe headache • Acute hypertension • Acute nausea or vomiting • Worsening neurological exam • Discontinue t-PA infusion and obtain stat CT non-contrast of brain • Restart infusion if no bleed

Conclusions

Ischemic Stroke: Get a complete history and present history succinctly and accurately to tele-neurologist Alert tele-neurologist of any concerns with regard to patient care or t-PA administration Keep Communication Lines Open