What is the time frame for administering thrombolysis in the emergency setting for acute ischemic stroke?

Time Window for Thrombolysis in Acute Ischemic Stroke

Intravenous thrombolysis with alteplase should be administered within 4.5 hours of symptom onset for eligible acute ischemic stroke patients, with the strongest evidence supporting treatment within 3 hours. 1, 2

Standard IV Thrombolysis Time Windows

0-3 Hour Window (Level A Evidence)

• IV alteplase (0.9 mg/kg, maximum 90 mg) must be offered to all eligible patients within 3 hours of symptom onset to improve functional outcomes 1, 2
• This represents the FDA-approved time window with the strongest evidence from the NINDS trial 1
• The number needed to treat ranges from 4.5 to 14.1 depending on how quickly treatment is initiated (0-90 minutes versus 181-270 minutes) 1
• Treatment should be initiated as rapidly as possible once the decision is made, as outcomes are strongly time-dependent 1, 2

3-4.5 Hour Window (Level B Evidence)

• IV alteplase should be considered for patients meeting ECASS III criteria between 3 to 4.5 hours after symptom onset 1, 2
• This extended window has additional exclusion criteria: age >80 years, oral anticoagulant use regardless of INR, NIHSS >25, or history of both stroke and diabetes 2
• As of the 2013 guideline publication, this extended window was not FDA-approved but had Level B recommendation support 1
• Pooled analysis demonstrates that benefit persists but decreases with time, making earlier treatment critical 3

Intra-arterial Thrombolysis Time Windows

Up to 6 Hours for Proximal Vessel Occlusions

• Intra-arterial thrombolysis may be initiated within 6 hours of symptom onset for patients with proximal cerebral artery occlusions (internal carotid artery, middle cerebral artery, vertebral artery, basilar artery) who do not meet IV alteplase eligibility criteria 1
• This approach is particularly applicable for large clot burden in proximal vessels 2
• The probability of good clinical outcome decreases as time to angiographic reperfusion increases, approaching that of untreated patients when treatment is completed at approximately 7 hours 1

Critical Time-Dependent Principles

Every Minute Counts

• All delays in treating patients must be avoided - the effectiveness of alteplase is highly time-dependent 1, 2
• The median door-to-needle time can be reduced to as low as 20 minutes with optimized systems 4
• Only blood glucose assessment must precede IV alteplase administration 2
• Do not delay IV thrombolysis to perform additional imaging beyond non-contrast CT or to assess for mechanical thrombectomy eligibility 2

Treatment Beyond Standard Windows

• Treatment initiated after 4.5 hours increases mortality and reverses the risk-benefit balance for IV thrombolysis 3
• For patients presenting 6-24 hours from last known well with large vessel occlusion, advanced imaging (CT perfusion or diffusion-weighted MRI) should determine eligibility for mechanical thrombectomy, not thrombolysis 2
• Meta-analyses suggest some benefit may extend to 6 hours, but no single trial has demonstrated effectiveness beyond 4.5 hours for IV therapy 5

Combined IV/IA Approach Timing

• Eligible patients should receive IV thrombolysis even if mechanical thrombectomy is being considered, without waiting to evaluate response 2
• Do not delay IV alteplase to prepare for intra-arterial therapy except in the setting of a clinical trial 1
• The combined approach may use reduced-dose IV alteplase (0.6 mg/kg) followed by intra-arterial therapy for large vessel occlusions 2

Common Pitfalls to Avoid

• Never withhold IV thrombolysis from eligible patients to deliver intra-arterial therapy, except in research settings 1
• Do not perform perfusion imaging or angiography before initiating IV thrombolysis, as this doubles in-hospital delays 4
• Blood pressure must be lowered below 185/110 mmHg before initiating thrombolysis 2
• Patients with blood glucose >11.1 mmol/L have a 36% risk of symptomatic intracranial hemorrhage and require careful consideration 2