What are the criteria for a patient with a moderate to severe stroke, as indicated by a National Institutes of Health Stroke Scale (NIHSS) score, to be a candidate for thrombolysis with tissue plasminogen activator (tPA)?

NIHSS Score Criteria for Thrombolysis Candidacy

Patients with acute ischemic stroke and a measurable neurological deficit on the NIHSS are candidates for IV tPA within 3 hours of symptom onset, with the strongest evidence supporting treatment in those with NIHSS scores ≥5, while patients with very mild strokes (NIHSS 0-2) should generally NOT receive thrombolysis due to increased hemorrhage risk without functional benefit. 1

Time-Based Treatment Algorithm

Within 0-3 Hours (Strongest Recommendation)

• Administer IV tPA 0.9 mg/kg (maximum 90 mg) for patients with measurable deficits, given as 10% bolus over 1 minute, then 90% infused over 60 minutes 2, 3
• This represents Level A evidence with the greatest absolute benefit when treatment is initiated earliest 1
• Blood pressure must be <185/110 mmHg before initiating therapy 2

Within 3-4.5 Hours (Conditional Recommendation)

• Consider IV tPA with additional ECASS III exclusion criteria 4, 2
• Symptomatic ICH risk increases to 7-8% in this window 4
• This represents Level B evidence with conditional recommendation 2, 3

NIHSS Score-Specific Guidance

NIHSS 0-2 (Very Mild Stroke)

Do NOT routinely administer thrombolysis in this population based on recent high-quality evidence 5, 6:

• Thrombolysis in NIHSS 0-1 patients was associated with 9-fold increased risk of symptomatic ICH (adjusted OR 9.32,95% CI 4.53-19.15) 6
• No improvement in excellent functional outcome at 90 days (adjusted OR 0.67,95% CI 0.5-0.9) 6
• NIHSS 0-2 patients had increased sICH risk without functional benefit 5
• These patients already achieve excellent outcomes (81.3%) without thrombolysis 7

NIHSS 3-5 (Mild Stroke)

Administer thrombolysis - this population demonstrates clear benefit 5:

• Significant improvement in 90-day functional independence (adjusted OR 3.284,95% CI 1.876-5.749, p<0.001) 5
• No significant increase in symptomatic ICH (adjusted OR 2.770,95% CI 0.313-24.51, p=0.360) 5
• Only 48.7% achieve excellent outcomes without treatment compared to 81.3% in NIHSS 0-2 group 7

NIHSS ≥12 (Moderate to Severe Stroke)

Strongly consider mechanical thrombectomy in addition to IV tPA 8:

• NIHSS ≥12 at admission predicts unfavorable functional outcome with thrombolysis alone (sensitivity 0.51, specificity 0.84, AUC 0.74) 8
• These patients likely have major vessel occlusion requiring endovascular intervention 9
• The NINDS trial threshold for measurable deficit was used, though baseline severity was imbalanced with more mild strokes in the tPA group 1

Critical Contraindications

Absolute Contraindications

• Severe uncontrolled hypertension (SBP >185 mmHg or DBP >110 mmHg) unresponsive to emergency treatment 2
• Any prior intracranial hemorrhage 2
• Ischemic stroke within 3 months 2
• Current use of direct oral anticoagulants (DOACs) - substantially elevated bleeding risk 3

Relative Contraindications

• History of chronic, severe, poorly controlled hypertension 2
• Significant hypertension (SBP >180 mmHg or DBP >110 mmHg) that responds to treatment 2

Post-Treatment Monitoring Protocol

Blood Pressure Management

• Maintain SBP ≤180 mmHg and DBP ≤105 mmHg for at least 24 hours post-thrombolysis 2
• Monitor every 15 minutes for first 2 hours, every 30 minutes for hours 2-8, then hourly from hours 8-24 2

Neurological Assessment

• Perform neurological checks every 15 minutes during infusion 2
• Every 30 minutes for 6 hours post-infusion 2
• Hourly from hours 6-24 2
• Admit all patients to ICU or stroke unit for intensive monitoring 2

Common Pitfalls to Avoid

Do not treat NIHSS 0-2 patients routinely - the most recent high-quality evidence demonstrates harm without benefit 5, 6. The original NINDS trials had a paucity of patients with NIHSS 0-4, creating equipoise that recent studies have now resolved against treatment in the NIHSS 0-2 subgroup 1.

Do not exceed 4.5 hours from symptom onset - treatment beyond this window is contraindicated (Grade 1B) 3.

Do not administer tPA if blood pressure cannot be controlled below 185/110 mmHg - this is an absolute contraindication that significantly increases hemorrhage risk 2.

The baseline symptomatic ICH rate with proper patient selection and dosing is 4-6%, but this increases substantially with protocol violations or in contraindicated populations 3.