What are the latest guidelines for managing acute ischemic stroke in adults and children, including recommended timing for computed tomography (CT) or magnetic resonance imaging (MRI) and vascular imaging, door‑to‑needle time, intravenous thrombolysis with alteplase (tPA) or tenecteplase dosing and therapeutic windows, criteria for mechanical thrombectomy (including large‑vessel occlusion, National Institutes of Health Stroke Scale score, modified Rankin Scale, DAWN and DEFUSE‑3 criteria), secondary prevention strategies, and stroke system‑of‑care recommendations?

Latest Guidelines for Acute Ischemic Stroke Management

The 2018 American Heart Association/American Stroke Association guidelines, updated in 2019, represent the current standard for acute ischemic stroke management, emphasizing rapid imaging, door-to-needle times under 60 minutes for IV alteplase, and mechanical thrombectomy for large-vessel occlusions within extended time windows up to 24 hours in selected patients. 1, 2

Prehospital and Emergency Medical Services

Stroke Recognition and Transport

• EMS should use validated stroke screening tools (FAST scale, Cincinnati Prehospital Stroke Scale, or Los Angeles Prehospital Stroke Screen) to rapidly identify suspected stroke patients 1
• Transport directly to certified stroke centers capable of administering IV alteplase and performing endovascular treatment, bypassing non-stroke hospitals when appropriate 1
• Document the exact "last known well" time during initial assessment, as this determines all time-sensitive treatment eligibility 3, 4

Regional Stroke Systems

• Regional systems must include: (a) facilities providing initial emergency care with IV alteplase capability, and (b) comprehensive centers performing endovascular stroke treatment with 24/7 availability 1

Emergency Department Protocol (First 60 Minutes)

Immediate Triage and Stabilization

• Triage stroke patients with the same urgency as acute myocardial infarction or severe trauma, regardless of deficit severity 3
• Stabilize airway, breathing, and circulation first; provide supplemental oxygen only if saturation falls below 94% 1, 3, 4
• Check capillary glucose immediately; treat hypoglycemia (glucose <60 mg/dL or 3.3 mmol/L) with IV dextrose before any other intervention 1, 3

Neuroimaging Requirements

• Obtain non-contrast CT or MRI within 25-30 minutes of arrival to exclude intracranial hemorrhage before initiating reperfusion therapy 1, 3, 5
• Perform CT angiography (CTA) from aortic arch to vertex immediately to identify large-vessel occlusion amenable to mechanical thrombectomy 1, 3, 4
• A physician with neuroimaging expertise must interpret the scan within 45 minutes of patient arrival 5
• Do not delay thrombolysis for advanced perfusion imaging (CT perfusion or MRI diffusion-perfusion) when eligibility is established on non-contrast CT 3

Laboratory Evaluation

• Obtain complete blood count, electrolytes, creatinine, PT/INR, aPTT, troponin, and electrocardiography, but do not delay IV alteplase while awaiting results unless clinical suspicion exists for bleeding disorder, thrombocytopenia, or recent anticoagulant use 1, 3
• Only blood glucose measurement must precede alteplase administration in all patients 1

Stroke Severity Assessment

• Use the National Institutes of Health Stroke Scale (NIHSS) in the emergency department to quantify deficit severity and guide treatment decisions 1

Intravenous Thrombolysis

Alteplase Dosing and Administration

• Administer IV alteplase 0.9 mg/kg (maximum 90 mg) with 10% given as bolus over 1 minute and the remainder infused over 60 minutes 1, 3
• Target door-to-needle time <60 minutes for ≥50% of patients (primary goal); a secondary goal of <45 minutes in ≥50% may be reasonable 1, 3
• Each 30-minute delay reduces the probability of favorable outcome by approximately 10.6% 3

Time Windows for IV Alteplase

• 0-3 hours from symptom onset: Strong recommendation (Class I, Level A) 1, 4
• 3-4.5 hours from onset: Recommended except in patients with all of the following: age >80 years, oral anticoagulant use regardless of INR, NIHSS >25, or history of both diabetes and prior stroke (Class I, Level B) 1, 4
• 4.5-9 hours with CT/MRI perfusion mismatch: Consider alteplase if mechanical thrombectomy is not indicated or planned 1
• Wake-up stroke or unclear onset >4.5 hours: Alteplase may be beneficial if MRI shows DWI-FLAIR mismatch and treatment initiated within 4.5 hours of symptom recognition 1

Blood Pressure Management for Thrombolysis

• Lower BP to <185/110 mmHg before initiating alteplase 1, 3
• Maintain BP ≤180/105 mmHg during infusion and for 24 hours post-treatment 1, 3
• Use labetalol or nicardipine for acute BP reduction 1

Post-Thrombolysis Monitoring

• Check neurological status and vital signs every 15 minutes during and for 2 hours after infusion, then every 30 minutes for 6 hours, then hourly until 24 hours 1, 3
• Admit to intensive care or stroke unit for continuous monitoring 1
• Obtain follow-up CT or MRI at 24 hours before starting anticoagulants or antiplatelet agents 1
• Delay placement of nasogastric tubes, indwelling bladder catheters, or intra-arterial pressure catheters if the patient can be safely managed without them 1

Tenecteplase as Alternative

• Tenecteplase 0.4 mg/kg single IV bolus might be considered as an alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion (Class IIb, Level B-R) 1
• Tenecteplase is given as a single bolus versus the 1-hour alteplase infusion 1
• Evidence suggests tenecteplase 0.25 mg/kg may provide superior excellent functional outcomes compared to alteplase 0.9 mg/kg 6, 7

Contraindications and Complications

• Frank hypodensity involving >1/3 of MCA territory on CT is a contraindication to alteplase 4
• Symptomatic intracranial hemorrhage occurs in approximately 6.4% of alteplase-treated patients 3

Management of Symptomatic Intracranial Bleeding (Class IIb, LOE C-EO)

• Stop alteplase infusion immediately 1
• Obtain CBC, PT/INR, aPTT, fibrinogen level, type and cross-match 1
• Emergent non-contrast head CT 1
• Administer cryoprecipitate 10 units over 10-30 minutes; additional dose if fibrinogen <200 mg/dL 1
• Tranexamic acid 1000 mg IV over 10 minutes OR ε-aminocaproic acid 4-5 g over 1 hour, then 1 g IV until bleeding controlled 1
• Obtain hematology and neurosurgery consultations 1

Management of Orolingual Angioedema (Class IIb, LOE C-EO)

• Maintain airway; intubation may not be necessary if edema limited to anterior tongue and lips 1
• Discontinue alteplase and hold ACE inhibitors 1
• Administer IV methylprednisolone 125 mg, IV diphenhydramine 50 mg, and ranitidine 50 mg IV or famotidine 20 mg IV 1
• If angioedema progresses, give epinephrine 0.3 mL (0.1%) subcutaneously or by nebulizer 1
• Consider icatibant 30 mg subcutaneously (may repeat at 6-hour intervals, maximum 3 doses in 24 hours) 1

Mechanical Thrombectomy

Indications for Thrombectomy (Class I, Level A)

Patients should receive mechanical thrombectomy with stent retrievers if all criteria are met: 1, 3, 4

• Age ≥18 years
• Pre-stroke modified Rankin Scale (mRS) 0-1
• Causative occlusion of internal carotid artery or MCA M1 segment
• NIHSS ≥6
• ASPECTS ≥6
• Groin puncture achievable within 6 hours of symptom onset

Extended Time Windows

• 6-16 hours from last known well: Thrombectomy recommended if patient meets DAWN trial criteria (age, NIHSS, infarct volume on CT/MRI) 1
• 6-24 hours from last known well: Thrombectomy recommended if patient meets DEFUSE-3 criteria (clinical-core mismatch or clinical-penumbra mismatch on CT perfusion or MRI) 1
• Age >80 years is not a contraindication; elderly patients derive significant benefit (common odds ratio 3.68; 95% CI 1.95-6.92) 4

Technical Recommendations

• Use stent-retriever devices (e.g., Solitaire FR, Trevo) as first-line mechanical thrombectomy devices over coil retrievers (Class I, Level A) 1, 3
• Use proximal balloon-guide catheter or large-bore distal-access catheter together with stent retriever to improve recanalization rates 1, 3
• Target final angiographic result of TICI 2b/3 (substantial or complete reperfusion) 1, 3
• Perform thrombectomy under conscious sedation or general anesthesia; either method is reasonable until further data available 1

Coordination with IV Thrombolysis

• Administer IV alteplase even if mechanical thrombectomy is planned; do not delay alteplase while preparing for endovascular procedure 1, 3
• Do not wait for clinical response to IV alteplase before proceeding with thrombectomy; delaying thrombectomy worsens outcomes (Class III, Level B-R) 1, 3

Blood Pressure During Thrombectomy

• Maintain BP ≤180/105 mmHg during and for 24 hours after the procedure (Class IIa, Level B-NR) 1
• In patients with successful reperfusion, it might be reasonable to maintain BP <180/105 mmHg (Class IIb, Level B-NR) 1

Intra-arterial Thrombolysis

• Intra-arterial alteplase may be considered as rescue therapy within 6 hours for MCA occlusion in patients with contraindications to IV alteplase (Class IIb, Level C-EO) 1, 4
• Mechanical thrombectomy with stent retrievers is recommended over intra-arterial thrombolysis as first-line therapy 1

Acute In-Hospital Management

Stroke Unit Care

• Admit all stroke patients to a geographically defined stroke unit with specialized multidisciplinary team (neurologists, specialized nurses, physiotherapists, occupational therapists, speech therapists, social workers) 1, 3, 4
• Maintain nurse-to-patient ratio of 1:2 for the first 24 hours; up to 30% of patients experience neurological deterioration during this period 4
• Stroke-unit care reduces mortality and disability across all stroke types, ages, and severities (Class I, Level A) 3

Antiplatelet Therapy

• For patients receiving IV alteplase: Delay aspirin for at least 24 hours until follow-up CT excludes intracranial hemorrhage, then start aspirin 150-325 mg daily 1, 3, 4
• For patients not receiving thrombolysis: Administer aspirin 160-325 mg within 24-48 hours of stroke onset 1, 3
• Do not administer antiplatelet agents or anticoagulants for 24 hours after alteplase due to increased bleeding risk 3

Blood Pressure Management (Non-Thrombolysis Patients)

• Withhold antihypertensives unless systolic BP >220 mmHg or diastolic BP >120 mmHg; a reasonable goal is to lower BP by approximately 15% during the first 24 hours (Class IIa, Level B) 4
• Emergency treatment of hypertension is indicated if concomitant acute myocardial ischemia, aortic dissection, or preeclampsia/eclampsia exists 1

Venous Thromboembolism Prophylaxis

• Administer subcutaneous low-molecular-weight heparin (e.g., enoxaparin 40 mg once daily) or unfractionated heparin 5000 IU twice daily for immobilized patients 1, 4
• Add intermittent pneumatic compression for additional VTE risk reduction 4
• Do not use elastic compression stockings for routine VTE prophylaxis (Class III, Level A) 4

Airway and Oxygenation

• Provide airway support and ventilatory assistance for patients with decreased consciousness or bulbar dysfunction 3, 4
• Tracheal intubation is indicated for compromised airway or insufficient ventilation due to impaired alertness or bulbar dysfunction 1

Fluid and Metabolic Management

• Maintain euvolemia with isotonic normal saline; avoid volume expanders for hemodilution 4
• Treat hyperthermia (>38°C) to prevent secondary brain injury 3
• Maintain blood glucose 140-180 mg/dL; avoid glucose-containing fluids unless patient is hypoglycemic 3, 4

Aspiration Prevention

• Perform swallowing screening before any oral intake to prevent aspiration pneumonia (compulsory quality indicator) 4
• For patients unable to swallow, place naso-enteric feeding tube within 24 hours; preferred over percutaneous endoscopic gastrostomy for first 2-3 weeks 4
• Perform oral hygiene at least three times daily and immediately after meals to decrease aspiration pneumonia 4

Early Mobilization

• Mobilize neurologically and hemodynamically stable patients within 24 hours of admission (ideally ≤52 hours); early mobilization reduces medical complications 4

Cardiac Monitoring

• Continuous cardiac telemetry for the initial 24 hours to detect new-onset atrial fibrillation and other arrhythmias 4
• Right-MCA strokes carry higher risk of cardiovascular complications (myocardial ischemia, atrial fibrillation, arrhythmias) 4

Decompressive Hemicraniectomy for Malignant Edema

Indications (Class I, Level A)

• Perform decompressive hemicraniectomy within 48 hours of symptom onset for patients with malignant cerebral edema 3
• Surgical criteria include: infarct >50% of MCA territory or lesion volume >150 cm³, radiologic evidence of significant edema/mass effect, and age 18-60 years (strongest evidence) 3
• Age 60-80 years may be considered (Class I, Level B) 3

Expected Outcomes

• Decompressive surgery reduces mortality by approximately 50% but most survivors have moderate-to-severe disability (mRS 3-4) 3
• In patients >60 years, surgery lowers mortality but none achieve good functional recovery (mRS 0-2) 3

Secondary Prevention

Antithrombotic Therapy

• Non-cardioembolic stroke: Prescribe clopidogrel 75 mg daily OR aspirin 25 mg + extended-release dipyridamole 200 mg twice daily rather than aspirin alone (Class I, Level A) 4
• Atrial fibrillation: Initiate oral anticoagulation at discharge (compulsory quality indicator); oral anticoagulants are superior to antiplatelet agents for preventing cardioembolic recurrence (Class I, Level A) 4
• Minor stroke (NIHSS ≤3-5) or high-risk TIA (ABCD² ≥4): Start dual antiplatelet therapy (aspirin + clopidogrel or ticagrelor) within 24 hours of symptom onset (Class I, Level B) 4

Blood Pressure Control

• Start antihypertensive medication in all patients regardless of baseline BP before discharge (compulsory quality indicator, Class I, Level A) 4

Lipid Management

• Prescribe high-intensity statin for all patients with ischemic stroke or TIA (Class I, Level A) 4
• Target LDL-cholesterol <1.8 mmol/L (approximately 70 mg/dL) (Class I, Level B) 4

Carotid Revascularization

• For symptomatic carotid stenosis ≥50% (NASCET criteria), perform carotid endarterectomy within 14 days of symptom onset (Class I, Level A) 4

Lifestyle Modifications

• Smoking cessation counseling for active smokers (Class I, Level B) 4
• Alcohol reduction to ≤2 drinks/day (men) or ≤1 drink/day (women) (Class I, Level B) 4
• Low- to moderate-intensity aerobic activity (approximately 10 minutes, ≥4 days/week) (Class I, Level B) 4
• Dietary sodium <2000 mg/day (Class I, Level B) 4

Cardiac Evaluation

• Obtain transthoracic echocardiography to assess for cardioembolic sources; consider transesophageal echocardiography if source suspected but not identified (Class IIa) 3

Quality Improvement and System Requirements

Door-to-Needle Time Goals

• Establish DTN time goals with primary target of ≤60 minutes in ≥50% of patients treated with IV alteplase 1
• A secondary goal of ≤45 minutes in ≥50% may be reasonable (Class IIb, Level C-EO) 1

Multidisciplinary Stroke Team

• Designate an acute stroke team including physicians, nurses, and laboratory/radiology personnel available 24/7 1
• Implement multicomponent quality improvement initiatives with ED education and multidisciplinary teams to safely increase IV thrombolytic treatment (Class I, Level A) 1

Certification and Monitoring

• Seek certification by independent external accreditation entity (e.g., The Joint Commission, state health departments) 1, 3
• Implement strategy to monitor stroke quality metrics including DTN time, stroke-unit admission rate, brain imaging completion, antiplatelet therapy at discharge, anticoagulation for atrial fibrillation, and swallowing screening 1, 4

24/7 Resource Availability

• Ensure availability of CT/MRI, CT angiography, neurosurgery, vascular surgery, interventional neuroradiology, and cardiology consultation 4
• For facilities lacking in-house imaging interpretation, use FDA-approved teleradiology/telestroke systems to enable rapid brain CT/MRI review (Class I, Level B) 3

Discharge Planning and Follow-up

Rehabilitation

• Conduct standardized screening evaluation during initial hospitalization to identify patients with residual impairments requiring rehabilitation 4
• Initiate rehabilitation planning involving caregivers within 24 hours; 50-70% of patients regain functional independence but 15-30% remain permanently disabled 4
• Arrange specialist stroke-rehabilitation team follow-up within 72 hours of discharge (Class I, Level A) 4

Long-term Follow-up

• Review health and social-care needs at 6 months and then annually (including patients in care homes) (Class I, Level A) 4
• Provide structured patient and family education about stroke causes, risk factors, warning signs, secondary prevention strategies, and proper EMS activation before discharge 4

Critical Pitfalls to Avoid

• Do not delay thrombolysis for advanced imaging (perfusion/diffusion MRI) when eligibility is established on non-contrast CT 3
• Do not use full-dose anticoagulation (IV or subcutaneous heparin) in acute ischemic stroke; it increases hemorrhage risk without improving outcomes (Class III, Level B) 3, 4
• Do not assume behavioral symptoms (confusion, agitation) are contraindications to thrombolysis; they may reflect the stroke itself 3
• Do not perform emergency carotid endarterectomy in acute ischemic stroke due to high peri-procedural risk (Class III, Level B) 3
• Do not rely on clinical characteristics alone to differentiate hemorrhagic from ischemic stroke; symptoms such as vomiting and severe headache are not specific 5
• Do not use routine indwelling urinary catheters due to heightened infection risk 4
• Do not use elastic compression stockings for VTE prophylaxis 4