What is the appropriate dosage and administration technique for intrapleural alteplase (tissue‑type plasminogen activator) via a chest tube in children?

Intrapleural Alteplase Administration in Children

For intrapleural fibrinolysis in children with parapneumonic effusion or empyema, administer alteplase 0.1 mg/kg (not to exceed 5-10 mg per dose) once daily via chest tube with a 1-hour dwell time, though twice-daily dosing may be used for more severe cases. 1

Dosing Protocol

Standard Dosing Regimen

• Dose: 0.1 mg/kg once daily 1
• Maximum dose: While not explicitly stated in pediatric guidelines, adult data and safety considerations suggest starting with 5 mg per dose, with potential escalation to 10 mg if needed 2
• Dwell time: 1 hour 1
• Frequency: Once daily is the evidence-based regimen, though twice-daily administration has been studied 3, 4

Alternative Dosing Considerations

• Some centers use twice-daily dosing (0.1 mg/kg every 12 hours) for more aggressive treatment, which has shown greater fluid mobilization in research studies 3, 4
• Earlier administration in the disease course produces better results than delayed treatment 3

Administration Technique

Step-by-Step Protocol

1. Preparation: Reconstitute alteplase and dilute to appropriate volume (typically 10-40 mL normal saline depending on chest tube size) 1

2. Instillation:

   • Clamp the chest tube
   • Instill the alteplase solution through the chest tube
   • Ensure the medication reaches the pleural space 1

3. Dwell period:

   • Keep chest tube clamped for 1 hour 1
   • Patient may be repositioned during dwell time to distribute medication throughout pleural space

4. Drainage:

   • Unclamp chest tube after 1-hour dwell
   • Resume standard chest tube drainage to gravity or suction 1

5. Duration:

   • Administer for 3 days (total of 3 doses with once-daily regimen) 1
   • May extend beyond 3 days if incomplete response, with benefit demonstrated up to 72 hours with repeated dosing 3

Important Clinical Considerations

Safety Profile

• Bleeding risk: Minimal in pediatric studies; transient blood-staining of drainage fluid is common but not clinically significant 1
• Pain management: Discomfort during instillation occurs in some patients; consider co-administering intrapleural bupivacaine if needed 1
• Contraindication: Do NOT use within 24 hours of traumatic chest tube insertion due to bleeding risk 1

Efficacy Expectations

• Treatment success rates of 98-100% in pediatric studies 4
• Significantly greater pleural fluid drainage compared to saline irrigation 3, 4
• Reduction in pleural fluid volume visible on imaging within 24-72 hours 3

When to Escalate Care

• Surgical referral indicated if: Persistent sepsis with ongoing pleural collection despite chest tube drainage, antibiotics, and fibrinolytic therapy 1
• Consider dose escalation (if starting at 5 mg) or increased frequency before proceeding to surgery 2

Critical Pitfall to Avoid

Do not confuse intrapleural dosing with systemic thrombolytic dosing. The intrapleural dose of 0.1 mg/kg (maximum 5-10 mg) is dramatically lower than systemic stroke dosing (0.9 mg/kg, maximum 90 mg) because the medication acts locally in the pleural space with minimal systemic absorption. 1, 5, 6

Comparison with Urokinase

While urokinase was the only fibrinolytic studied in randomized controlled trials in children and remains guideline-recommended, it is no longer available in North America. 1 Alteplase has demonstrated equivalent or superior efficacy with greater pleural fluid drainage in comparative studies, making it the practical alternative. 1, 4