Clinical Context

• Population: Adults with acute ischemic stroke
• Setting: Emergency Department
• Decision: Whether to administer IV thrombolytics (tPA/tenecteplase)

Best Evidence

Guidelines / consensus

• According to multiple stroke protocols (e.g., AHA/ASA), thrombolysis is recommended when patients present within 3 hours (up to 4.5 hours in select cases) of symptom onset with measurable deficits and without contraindications ^1^2.

Key Trials

• NINDS Trial (treated within 3 hrs):
  • Intervention vs control: IV tPA versus placebo
  • Primary outcome: Improved functional outcomes at 3 months
  • Limitations: Early hemorrhagic complications with a risk-benefit balance ^2
• ECASS Trial (treated within 4.5 hrs):
  • Intervention vs control: tPA extended window up to 4.5 hrs vs placebo
  • Primary outcome: Favorable mRS outcomes at 90 days
  • Limitations: Increased risk of intracranial hemorrhage, particularly in older patients or those with severe strokes ^3

Bedside Application

• Use if:
  • The patient presents with a clinically measurable stroke (often NIHSS >4) within 3 hours of symptom onset (or up to 4.5 hours in select cases with adjusted criteria)
  • CT/CTA/CTP imaging excludes hemorrhage and large established infarction (typically <1/3 of MCA territory)
  • Blood pressure is ≤180/110 mmHg (or is controllable to this range before treatment)
  • The patient is not significantly disabled pre-stroke (e.g., modified Rankin Score < 4) and has no contraindicated coagulation issues
• Avoid if:
  • There is evidence of intracranial hemorrhage or large established infarct on imaging
  • Uncontrolled hypertension persists despite treatment
  • The patient is on anticoagulation with abnormal coagulation markers (e.g., warfarin with INR ≥1.7 or recent DOAC use within safe windows)
  • Other absolute contraindications such as active bleeding, recent surgery/trauma, or prior intracranial hemorrhage exist
• Shared decision-making points:
  • Discuss the potential 30% reduction in moderate to severe disability versus the 5% increased risk of intracranial hemorrhage
  • Clarify the time-sensitive nature of treatment, noting that “time is brain”

Controversies

• The extension of the therapeutic window from 3 to 4.5 hours remains under continuous review; patient selection in the extended period (e.g., age >80, combination of previous stroke and diabetes, high NIHSS) requires individual specialist assessment ^2.

Practical Approach

1. Rapidly assess for stroke symptoms with NIHSS, ensure clear time of onset, and initiate emergent imaging (non-contrast head CT to rule out hemorrhage plus additional vascular/imaging studies if available).
2. Evaluate for contraindications including BP, anticoagulation status, blood glucose, and pre-stroke functional status, then involve neurology to confirm eligibility prior to thrombolytic administration.