Acute Management of Ischemic Stroke

Please refer to the Guidelines for the Early Management of Patients With Acute Ischemic Stroke, published in Stroke from 2018 for complete recommendations.

• What follows are some helpful considerations for clinicians but this information is not exhaustive and is simply designed to highlight certain aspects of the 2018 Guidelines.

• IV alteplase 0.9 mg/kg, maximum dose 90 mg over 60 minutes with initial 10% of dose given as bolus over 1 minute.
• Be prepared to treat potential emergent adverse effects, including bleeding complications and angioedema that may cause partial airway obstruction.
• IV Alteplase is recommended for use up to 4.5 hours from stroke onset; although its original FDA approval for use up to 3 hours from onset of stroke symptoms.
• In the original NINDS Trial, patients treated with IV thrombolysis had 30% greater likelihood of a favorable outcome (minimal or no disability) at 3 months compared with patients who were not treated.

• The following CT changes have historically been considered to be contraindications to IV alteplase but should NOT:
• Acute hypoattenuation or early ischemic changes are NOT a contraindication to IV alteplase.
• Hyperdense MCA sign is NOT a contraindication to IV alteplase.
• Imaging criteria should NOT be used to determine time of onset for administration of IV alteplase.
• Imaging beyond Noncontrast Head CT (eg, multimodal CT, MRI, and perfusion imaging) should NOT delay administration of IV alteplase.
• Initiate IV alteplase BEFORE performing noninvasive vascular imaging (eg, CTA).
• In patients without a history of renal disease, a creatinine is NOT needed prior to CTA.
• In patients who are < 6 hours after stroke onset, CT perfusion to determine eligibility for mechanical thrombectomy is NOT recommended.

• Blood glucose is the only measurement that MUST precede IV alteplase administration in all patients.
• IV alteplase is contraindicated if glucose < 50 or > 400.
• Once blood glucose is brought within range, IV alteplase can be administered, if still appropriate.
• If there is suspicion of coagulopathy, platelet count or other coagulation testing may be indicated prior to IV alteplase administration, but if no abnormality is suspected, treatment should not be delayed while waiting for hematologic or coagulation testing.

The following are contraindications to IV alteplase:

• Glucose < 50 or > 400
• Once blood glucose is brought within range, IV alteplase can be administered, if still appropriate.
• Uncontrolled HTN
• Once BP is safely lowered to <185/110 mm Hg), IV alteplase can be administered, if still appropriate.
• Subarachnoid hemorrhage
• Intra-axial intracranial neoplasm (tumor in the brain, itself)
• Coagulopathy (platelets <100 000/mm3, INR >1.7, aPTT >40 s, or PT >15 s)
• Treatment dose of low molecular weight heparin (LMWH) w/in the previous 24 hours
• Thrombin inhibitors (eg, dabigatran) or factor Xa inhibitors (eg, rivaroxaban, apixaban and edoxaban); HOWEVER, the 2018 Guidelines provide recommendations on how to assess for potential inclusion of patients who have recently taken these medications.
• Glycoprotein IIb/IIIa receptor inhibitors (eg, abciximab, eptifibatide, and tirofiban) should not be CONCURRENTLY administered with IV alteplase.
• Infective endocarditis
• Aortic arch dissection
• History of any of the following:
• Intracranial hemorrhage (at any time in the patient's history)
• Ischemic stroke, severe head trauma, or intracranial/intraspinal surgery (any of these w/in the past 3 months)
• GI malignancy or GI bleed (w/in the past 3 weeks)

Listed below are some of the most common presenting conditions that were historically considered to be contraindications to IV alteplase but should NOT be; HOWEVER, the 2018 Guidelines address many nuanced clinical conditions and whether or not they should be inclusion/exclusion criteria for IV alteplase.

• Early improvement, alone, should NOT be an exclusion for IV alteplase.
• If the patient has early improvement but remains moderately impaired, IV alteplase should still be given.
• Seizure at onset should NOT be an exclusion for IV alteplase.
• If the deficits are secondary to stroke (NOT post-ictal), IV alteplase should still be given.
• Dural puncture within the previous 7 days is NOT a contraindication to IV alteplase.
• Extracranial cervical dissections are NOT a contraindication to IV alteplase.
• Unruptured, unsecured brain aneurysms that are < 10 mm are NOT a contraindication to IV alteplase.

• The time window for mechanical thrombectomy is now 24 hours in patients with a large vessel anterior circulation acute ischemic stroke when they meet imaging (eg, CTP, DW-MRI, or MRI perfusion) and other eligibility criteria used in select randomized control trials (eg, DAWN and DEFUSE 3).
• Of the options with mechanical thrombectomy, stent retrievers are the first choice.
• Stent retrievers are specifically indicated in preference to the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) device.
• Mechanical thrombectomy with stent retrievers is recommended over intra-arterial thrombolysis as first-line therapy BUT initial, additional treatment with intra-arterial thrombolysis can be beneficial for carefully selected patients with major MCA strokes of < 6 hours’ duration.

• No single antiplatelet agent (aspirin, clopidogrel, or aspirin plus extended-release dipyridamole) is preferred over another.
• In patients presenting with minor stroke, treat with dual antiplatelet therapy (aspirin and clopidogrel) for up to 90 days, for secondary stroke prevention.
• It is NOT recommended that antiplatelet therapy be added to anticoagulation (other than in angina and coronary artery stenting).
• In atrial fibrillation, it is generally reasonable to initiate oral anticoagulation within 4 to 14 days after the onset of stroke.
• Unless clinically contraindicated, antiplatelet or anticoagulation therapy may be continued in hemorrhagic transformation of ischemic stroke.
• For patients with acute ischemic stroke and extracranial carotid or vertebral arterial dissection, treatment with either antiplatelet or anticoagulant therapy for 3 to 6 months may be reasonable.
• For those patients treated with IV alteplase, aspirin administration is generally delayed for 24 hours, unless clinically indicated.

• High-Intensity Statin (eg, Atorvastatin 40-80 mg or Rosuvastatin 20-40 mg ) is recommended for secondary stroke prevention, especially in patients who are < 75 years old and have atherosclerotic, cardiovascular disease.
• In patients > 75 years old and in those who don't tolerate high-intensity statin therapy, dose-adjustments should be considered (rather than total discontinuation of statin therapy).

• In immobile stroke patients without contraindications, intermittent pneumatic compression (IPC) + routine care (aspirin and hydration) is recommended WHEREAS the overall benefit of prophylactic-dose subcutaneous heparin (unfractionated heparin [UFH] or LMWH) is offset by the increased risk of hemorrhage (thus, prophylactic-dose subcutaneous heparin is not a recommended management option for DVT prevention).

• Labetalol 10–20 mg IV over 1–2 min (may repeat 1 time)
• Nicardipine 5 mg/h IV, titrate up by 2.5 mg/h every 5–15 min, maximum 15 mg/h
• Clevidipine 1–2 mg/h IV, titrate by doubling the dose every 2–5 min until desired BP reached; maximum 21 mg/h
• Hydralazine
• Enalapril

• Stop alteplase infusion
• Check CBC, PT/INR, aPTT, fibrinogen level, and type and cross-match
• Order STAT Noncontrast Head CT
• Administer cryoprecipitate (includes factor VIII)
• 10 U infused over 10–30 min (onset in 1 hr, peaks in 12 hr)
• Administer additional dose for fibrinogen level of <200 mg/dL
• Tranexamic acid 1000 mg IV infused over 10 min OR aminocaproic acid 4–5 g over 1 hr, followed by 1 g IV until bleeding is controlled (peak onset in 3 hr)
• Consult Hematology and Neurosurgery
• Supportive therapy: BP management, ICP, CPP, MAP, temperature, and glucose control.

Powers, William J., Rabinstein, Alejandro A., Ackerson, Teri, et. al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association Stroke 2018; January 24, 2018