2. Dr Payam Sasannejad, Neurologist Assistant Professor of mums Intravenous thrombolytic therapy in acute ischemic stroke

4. 1.9 million neurons 14 billion synapses 7.5 miles myelinated fibers In a Typical Acute Ischemic Stroke, Every Minute Until Reperfusion the Brain Loses:

6. Recanalization recanalization and restoration of cerebral blood flow : desired immediate result of thrombolytic therapy Recanalization is associated with improved outcome and reduced mortality in acute ischemic stroke Spotaneous Intravenous thrombolysis Intra-arterial thrombolysis Combined intravenous and intra-arterial thrombolysis Mechanical

7. Intravenous rt-PA is recommended for selected patients who may be treated within 3 hours of onset of ischemic stroke (Class I Recommendation, Level of Evidence A). rt-PA should be administered to eligible patients who can be treated in the time period of 3 to 4.5 hours after stroke (Class I Recommendation, Level of Evidence B). AHA/ASA Guideline Recommendations

9. "Time is brain" the sooner intravenous rt-PA treatment, the more likely it is to be beneficial

10. "Time is brain" Guidelines recommend that the elapsed time to the start of rt-PA infusion should be ≤60 minutes from the time of patient arrival in the emergency department

11. "Time is brain" The following in-hospital timeline is suggested as a goal for all patients with acute ischemic stroke who are eligible for treatment with intravenous rt-PA: ● Evaluation by physician - 10 minutes ● Stroke or neurologic expertise contacted, ie, stroke team - 15 minutes ● Head CT or MRI scan - 25 minutes ● Interpretation of neuroimaging scan - 45 minutes ● Start of treatment - 60 minutes from arrival

12. "Time is brain"  Other items that can lead to delay include: initial telephone triage by the stroke physician obtaining and waiting for results of blood and laboratory tests obtaining consent treating hypertension (ie, systolic blood pressure ≥185 mmHg or diastolic ≥110 mmHg) delivery of rt-PA from the pharmacy to the bedside

13. "Time is brain" In the United States 22 percent of all ischemic stroke patients present within 3 hours only about 8 percent meet all other eligibility criteria for rt-PA treatment

14. Eligibility criteria for the treatment of acute ischemic stroke with recombinant tissue plasminogen activator Inclusion criteria Clinical diagnosis of ischemic stroke causing measurable neurologic deficit Onset of symptoms <4.5 hours before beginning treatment; if the exact time of stroke onset is not known, it is defined as the last time the patient was known to be normal Age ≥18 years

15. Exclusion criteria Historical Significant stroke or head trauma in the previous three months Previous intracranial hemorrhage Intracranial neoplasm, arteriovenous malformation, or aneurysm Recent intracranial or intraspinal surgery Arterial puncture at a noncompressible site in the previous seven days

16. Exclusion criteria Clinical Symptoms suggestive of subarachnoid hemorrhage Persistent blood pressure elevation (systolic ≥185 mmHg or diastolic ≥110 mmHg) Serum glucose <50 mg/dL (<2.8 mmol/L) Active internal bleeding Acute bleeding diathesis, including but not limited to conditions defined in 'Hematologic‘

17. Exclusion criteria Hematologic Platelet count <100,000/mm 3 Current anticoagulant use with an INR >1.7 or PT >15 seconds Heparin use within 48 hours and an abnormally elevated aPTT Current use of a direct thrombin inhibitor or direct factor Xa inhibitor with evidence of anticoagulant effect by laboratory tests such as aPTT, INR, ECT, TT, or appropriate factor Xa activity assays

18. Exclusion criteria Head CT scan Evidence of hemorrhage Evidence of a multilobar infarction with hypodensity involving >33 percent of the cerebral hemisphere subtle or small areas of hypodensity, loss of gray-white distinction, obscuration of the lentiform nucleus, and the presence of a hyperdense artery sign

20. Relative exclusion criteria Only minor and isolated neurologic signs Rapidly improving stroke symptoms Major surgery or serious trauma in the previous 14 days Gastrointestinal or urinary tract bleeding in the previous 21 days Myocardial infarction in the previous three months Seizure at the onset of stroke with postictal neurologic impairments Pregnancy

21. Additional relative exclusion criteria for treatment from 3 to 4.5 hours from symptom onset Age >80 years Oral anticoagulant use regardless of INR Severe stroke (NIHSS score >25) Combination of both previous ischemic stroke and diabetes mellitus

22. The 2013 AHA/ASA guidelines: under some circumstances and with careful consideration of risk- to-benefit, patients may receive fibrinolytic therapy despite the presence of one or more relative contraindications physicians with expertise in acute stroke care may modify the eligibility criteria

23. consensus patients who have a persistent neurologic deficit that is potentially disabling, despite improvement of any degree, should be treated with tPA in the absence of other contraindications. following should be considered disabling deficits: ● Complete hemianopia: ≥2 on the NIHSS question 3 ● Severe aphasia: ≥2 on NIHSS question 9 ● Visual or sensory extinction: ≥1 on NIHSS question 11 ● Any weakness limiting sustained effort against gravity : ≥2 on NIHSS question 5 or 6 ● Any deficits that lead to a total NIHSS >5 ● Any remaining deficit considered potentially disabling by the patient, family, or the treating practitioner

24. rapidly improving stroke symptoms (RISS) as an exclusion for tPA treatment only for patients who improve to the degree that any remaining deficits seem nondisabling thrombolytic treatment should not be delayed by continued monitoring for improvement

25. Some experts advocate a more rational use of thrombolytic therapy based on pathophysiologic information from modern imaging studies vascular lesion and the location extent reversibility of brain ischemia Such an approach may be considered in expert stroke centers with access to modern MRI, CT, and ultrasound based technologies

27. Informed consent Some patients will accept any risk Others are more risk averse and prefer to accept disability discussion of the risks and benefits with the patient and family (neurologic deficits caused by acute stroke often preclude obtaining informed consent from the patient) rt-PA is an approved therapy for acute stroke; consent is not required to administer rt-PA as an emergent therapy for eligible patients if surrogate consent is not possiblert-PA

28. MANAGEMENT OF BLOOD PRESSURE Strict blood pressure control is critical prior to and during the first 24 hours after thrombolytic therapy The blood pressure must be at or below 185 mmHg systolic and 110 mmHg diastolic before administering rt-PA intravenous agents: labetalol or nicardipine Alternative agents: hydralazine and enalaprilat If intravenous treatment does not bring the blood pressure into the acceptable range, the patient should not be treated with rt-PA

30. Dosing A dedicated intravenous line is required for rt-PA, and all patients should have at least one additional large bore intravenous line ● The rt-PA dose is calculated at 0.9 mg/kg of actual body weight, with a maximum dose of 90 mg ● Ten percent of the dose is given as an intravenous bolus over one minute and the remainder is infused over one hour

31. Monitoring All patients should be admitted to an intensive care unit or stroke unit for at least 24 hours of close neurologic and cardiac monitoring Important measures during the first 24 hours of rt-PA treatment:  Vital signs and neurologic status: every 15 minutes for two hours, then every 30 minutes for six hours, then every 60 minutes until 24 hours from the start of rt-PA treatment  Blood pressure: at or below 180/105 mmHg during the first 24 hours  Anticoagulant and antithrombotic agents, such as heparin, warfarin, or antiplatelet drugs, should not be administered for at least 24 hours after the rt-PA infusion is completed.  Placement of intra-arterial catheters, indwelling bladder catheters, and nasogastric tubes should be avoided for at least 24 hours if the patient can be safely managed without them  A follow-up noncontrast CT (or MRI) brain scan: 24 hours after rt-PA is initiated before starting treatment with antiplatelet or anticoagulant agents

32. COMPLICATIONS Most complication: symptomatic intracerebral hemorrhage (5 to 7 percent) Additional complications: o Asymptomatic intracerebral hemorrhage o systemic bleeding o angioedema

33. symptomatic intracerebral hemorrhage sudden neurologic deterioration decline in level of consciousness new headache, nausea and vomiting sudden rise in blood pressure after thrombolytic therapy In these patients: Discontinuation of the rt-PA infusion noncontrast head CT or MRI scan Blood drawn for typing and cross matching measurement of PT, PTT, platelet count, and fibrinogen ● 10 units of cryoprecipitate to increase the levels of fibrinogen and factor VIII ● 6-8 units of platelets