What is the recommended acute management for an adult presenting with an acute ischemic stroke within 4.5 hours, including rapid non‑contrast head CT or MRI, intravenous alteplase (tissue plasminogen activator, tPA) dosing and contraindications, blood pressure targets before and after thrombolysis, and criteria for endovascular mechanical thrombectomy?

Acute Ischemic Stroke Management Within 4.5 Hours

For adults presenting with acute ischemic stroke within 4.5 hours of symptom onset, immediately obtain a non-contrast head CT to exclude hemorrhage, then administer IV alteplase 0.9 mg/kg (maximum 90 mg) with 10% as a bolus over 1 minute and 90% infused over 60 minutes, provided blood pressure is lowered to <185/110 mmHg before treatment and maintained <180/105 mmHg for 24 hours afterward; proceed directly to mechanical thrombectomy evaluation with CT angiography if large vessel occlusion is suspected, without waiting for alteplase response. 1, 2

Immediate Imaging Protocol

Primary Imaging Requirements

• Perform non-contrast CT of the head immediately upon arrival—this is the only mandatory imaging before alteplase administration. 3, 2 The primary goal is to distinguish hemorrhagic from ischemic stroke and exclude intracranial hemorrhage. 3
• Non-contrast CT is preferred over MRI because it is faster, more widely available, and minimizes treatment delays. 2 Target completion within 15–20 minutes of patient arrival. 4
• The only laboratory test required before alteplase is bedside blood glucose measurement—do not delay treatment for complete laboratory panels. 1, 2, 4

Additional Imaging for Thrombectomy Candidates

• If the patient presents within 6 hours and has clinical signs suggesting large vessel occlusion (severe deficits, NIHSS ≥6, cortical symptoms), immediately perform CT angiography from aortic arch to vertex after the non-contrast CT. 3, 2 This identifies proximal arterial occlusions amenable to endovascular therapy. 3
• Do not delay alteplase administration to obtain CTA—these studies should be performed in rapid sequence. 2

Intravenous Alteplase Administration

Dosing Protocol

• Alteplase dose: 0.9 mg/kg with an absolute maximum of 90 mg total. 1, 2, 4
• Administer 10% of the calculated dose (0.09 mg/kg) as an IV bolus over exactly 1 minute. 1, 2
• Infuse the remaining 90% (0.81 mg/kg) continuously over 60 minutes. 1, 2

Time Window Eligibility

0–3 Hour Window (Class I, Level A):

• All patients ≥18 years with measurable neurological deficit are eligible regardless of age or stroke severity (NIHSS score). 1, 2
• Patients >80 years old are eligible in this window. 1
• High NIHSS scores (severe strokes, even NIHSS >25) do not contraindicate treatment. 3, 1
• Prior use of single or dual antiplatelet therapy (aspirin, clopidogrel) is not a contraindication. 1
• End-stage renal disease patients on hemodialysis with normal aPTT are eligible. 1

3–4.5 Hour Window (Class I, Level B-R):

• Same eligibility as 0–3 hours except exclude patients with any of the following: 1, 2, 4
  • Age >80 years
  • Current oral anticoagulant use (regardless of INR)
  • NIHSS >25
  • Combined history of both diabetes and prior stroke
• All other standard eligibility criteria continue to apply. 1

The evidence supporting the 3–4.5 hour window comes from pooled analysis of ECASS-1, ECASS-2, ECASS-3, and ATLANTIS trials, demonstrating increased favorable outcomes (OR 1.31) without increased mortality. 5

Absolute Contraindications

• Intracranial hemorrhage on CT imaging. 1, 2
• Ischemic stroke within the prior 3 months. 1, 2
• Severe head trauma within the prior 3 months. 1
• Extensive hypodensity involving >1/3 of the middle cerebral artery territory on CT (ASPECTS <6). 1, 2
• Unclear or unwitnessed symptom onset exceeding the applicable time window. 1

Blood Pressure Management

Pre-Thrombolysis Requirements

• Blood pressure must be lowered to <185/110 mmHg before initiating alteplase. 1, 2, 4 This is an absolute requirement—do not start the infusion until this target is achieved. 2
• Use titratable IV agents such as labetalol or nicardipine for rapid, controlled BP reduction. 2, 4
• Confirm blood pressure stability at the target before administering the alteplase bolus. 1

Post-Thrombolysis Management

• Maintain blood pressure <180/105 mmHg for the first 24 hours after alteplase infusion. 1, 2, 4
• Monitor blood pressure every 15 minutes for the first 2 hours, every 30 minutes for the next 6 hours, then hourly up to 24 hours. 1
• If severe headache, acute hypertension, nausea, or vomiting occur during or after infusion, stop alteplase immediately and obtain emergent repeat CT. 1, 2, 4

Critical Pitfall: Aggressive lowering of blood pressure below these thresholds should be avoided because cerebral perfusion in acute stroke is pressure-dependent and excessive reduction may worsen ischemia. 2

Mechanical Thrombectomy Criteria

Indications (0–6 Hour Window)

• Age ≥18 years. 2
• Pre-stroke modified Rankin Scale (mRS) 0–1 (functionally independent). 2
• Internal carotid artery (ICA) or M1 segment middle cerebral artery occlusion on CTA. 2
• NIHSS ≥6. 2
• ASPECTS ≥6 on non-contrast CT. 2
• Ability to achieve groin puncture within 6 hours of symptom onset. 2

Extended Window (6–24 Hours)

• Anterior circulation large vessel occlusion with favorable advanced imaging showing core-penumbra mismatch on CT perfusion or MRI diffusion-weighted imaging. 2
• Small ischemic core relative to clinical deficit severity. 2

Coordination with Thrombolysis

• Administer IV alteplase even when mechanical thrombectomy is planned (bridging therapy). 1, 2 The combination provides optimal outcomes. 1
• Do not wait for a response to alteplase before proceeding to angiography—coordinate both interventions in parallel. 2, 4 Delaying thrombectomy to assess alteplase response worsens outcomes. 1, 2
• Target groin puncture within 90 minutes of code-stroke activation for thrombectomy-eligible patients. 4

Post-Alteplase Monitoring and Safety

Neurological Monitoring

• Assess neurological status every 15 minutes during the alteplase infusion. 1, 4
• Continue monitoring every 30 minutes for the subsequent 6 hours, then hourly until 24 hours post-treatment. 1
• Obtain emergent repeat CT if the patient develops neurological deterioration, severe headache, or hypertensive spikes. 1, 2, 4

Antithrombotic Restrictions

• Avoid all antithrombotic agents (aspirin, clopidogrel, heparin, oral anticoagulants) for the first 24 hours after alteplase. 1, 2, 4
• Obtain a follow-up CT scan at 24 hours before starting any antiplatelet or anticoagulant therapy. 1

Procedural Delays

• Delay placement of nasogastric tubes, indwelling bladder catheters, and intra-arterial pressure catheters until after the 24-hour monitoring period. 1

Hemorrhagic Complications

• Symptomatic intracerebral hemorrhage occurs in 3.3% of patients treated according to protocol. 6 Real-world data from the STARS study showed favorable outcomes (mRS 0–1) in 35% and functional independence (mRS 0–2) in 43% at 30 days. 6
• Be aware of angioedema as a potential adverse effect that can cause partial airway obstruction. 1

Glucose Management

• Blood glucose must be >50 mg/dL before alteplase administration. 1
• Treat hypoglycemia (<60 mg/dL) immediately with IV dextrose before any other intervention. 2
• Hyperglycemia (>11.1 mmol/L or >200 mg/dL) significantly increases risk of symptomatic intracerebral hemorrhage (36% risk). 1 Target glucose 140–180 mg/dL during the first 24 hours. 2

Common Pitfalls to Avoid

• Never delay alteplase for "complete" laboratory results—only bedside glucose is required. 1, 2, 4 Protocol violations in the STARS study included unnecessary delays for laboratory work. 6
• Do not withhold alteplase from patients on single or dual antiplatelet therapy. 1 The benefit outweighs the modest increase in hemorrhage risk. 2
• Do not exclude patients based solely on advanced age (>80 years) if they present within 3 hours. 1 Age >80 is only an exclusion criterion for the 3–4.5 hour window. 1, 2
• Do not use permissive hypertension in thrombolysis candidates—strict BP control is mandatory. 2, 4 The <185/110 mmHg pre-treatment and <180/105 mmHg post-treatment targets are absolute requirements. 1, 2
• Target door-to-needle time <60 minutes for at least 90% of patients, with a median goal of 30 minutes. 4 Every 15-minute delay reduces the likelihood of favorable outcome. 1

Institutional Requirements

• The effectiveness of alteplase is less well established in hospitals lacking organized stroke systems including 24/7 rapid CT availability, dedicated stroke team, continuous neurological monitoring, blood pressure management protocols, and neurosurgical consultation. 1