When should tissue plasminogen activator (tPA) be administered in acute ischemic stroke based on the National Institutes of Health Stroke Scale (NIHSS) score?

Administration of tPA in Acute Ischemic Stroke Based on NIHSS Score

IV tPA should be offered to acute ischemic stroke patients who meet NINDS inclusion/exclusion criteria and can be treated within 3 hours after symptom onset, and should be considered for patients who meet ECASS III criteria for treatment between 3 to 4.5 hours after symptom onset, regardless of specific NIHSS score thresholds. 1

Time Windows for tPA Administration

• IV tPA should be administered within 3 hours of symptom onset as a Level A recommendation, with evidence showing improved functional outcomes 1
• IV tPA may be administered between 3-4.5 hours of symptom onset as a Level B recommendation, with evidence showing potential benefit but higher risk 1
• Once the decision is made to administer IV tPA, the patient should be treated as rapidly as possible within these time windows 1

Efficacy Based on NIHSS Score

• The NINDS trial demonstrated benefit across a range of stroke severities, though patients with NIHSS scores between 5-22 showed the most consistent benefit 1
• Patients with mild stroke (NIHSS 0-4) were underrepresented in the original NINDS trials, creating some uncertainty about benefit in this population 1
• For patients with measurable neurological deficit, IV tPA within 3 hours showed a 12% absolute increase in patients with minimal or no disability (number needed to treat = 8.3) 1

Risk Considerations

• Symptomatic intracerebral hemorrhage (sICH) occurs in approximately 6.4% of patients treated with IV tPA compared to 0.6% with placebo within the first 3 hours 2
• The risk of sICH increases to approximately 7-8% when tPA is administered in the 3-4.5 hour window 1
• Despite the increased risk of sICH, mortality at 3 months was not significantly different between tPA and placebo groups (17% vs 21%, p=0.30) 1

Administration Protocol

• IV tPA dose is 0.9 mg/kg (maximum 90 mg), with 10% given as a bolus and the remaining 90% infused over 60 minutes 1
• Patient selection should follow established inclusion/exclusion criteria from either NINDS (for 0-3 hour window) or ECASS III (for 3-4.5 hour window) 1

Special Considerations

• Shared decision-making between the healthcare team and patient/surrogate should include discussion of potential benefits and risks prior to tPA administration (Level C recommendation) 1
• The number needed to treat for a favorable outcome in the 3-4.5 hour window is 14 (95% CI 7 to 244), compared to 8.3 in the 0-3 hour window 1
• The number needed to harm for symptomatic ICH in the 3-4.5 hour window is 23 (95% CI 13 to 78) 1

Common Pitfalls to Avoid

• Delaying treatment while waiting for improvement in patients with mild symptoms - earlier treatment is associated with better outcomes 1
• Excluding patients based solely on age - elderly patients can benefit from tPA despite having higher baseline risk 1
• Failing to recognize that the effectiveness of tPA may be less established in institutions without proper systems in place to safely administer the medication 1

Clinical Decision Algorithm

1. Confirm acute ischemic stroke with measurable deficit on NIHSS
2. Determine time of symptom onset
3. Assess for contraindications based on appropriate criteria (NINDS for 0-3 hours, ECASS III for 3-4.5 hours)
4. For patients within 3 hours: Strongly consider tPA regardless of NIHSS score if no contraindications 1
5. For patients between 3-4.5 hours: Consider tPA with additional exclusion criteria (age >80, NIHSS >25, oral anticoagulant use, or history of both diabetes and prior stroke) 1
6. Administer tPA as rapidly as possible once the decision is made 1

Remember that while the NIHSS score helps quantify stroke severity, there is no specific NIHSS threshold that determines tPA eligibility - the decision should be based primarily on time from symptom onset and absence of contraindications 1.