Standard Intrapleural Streptokinase Dosing for Adult Empyema
The standard dose of intrapleural streptokinase for adult empyema is 250,000 IU diluted in 100 mL normal saline, administered twice daily for 3 days, with a 3-4 hour dwell time before unclamping the chest tube. 1
Dosing Protocol
Standard regimen:
- Dose: 250,000 IU streptokinase in 100 mL normal saline 1, 2, 3
- Frequency: Twice daily 1
- Duration: 3 days (total of 6 doses) 1
- Dwell time: Clamp chest tube for 3-4 hours after instillation 2, 3
Administration Technique
- Instill through existing chest tube after initial drainage has slowed (typically <100 mL/24 hours) 2, 4
- Ensure chest tube patency before attributing poor drainage to loculations—flush with 20-50 mL normal saline if blockage suspected 1
- Unclamp after dwell period and monitor drainage volume 2, 3
Expected Response
- Drainage typically increases dramatically in first 24 hours after initial dose (mean 334-380 mL versus 42.5 mL pre-treatment) 5, 4
- Complete resolution achieved in 73-85% of patients without surgery 2, 3, 4
- Clinical and radiological improvement should be assessed at 5-8 days 1
Critical Safety Considerations
Streptokinase-specific warnings:
- Patients must receive a streptokinase exposure card and should only receive urokinase or tPA for any future systemic indications due to antibody formation 1
- Fever occurs commonly (particularly with streptokinase) and may be difficult to distinguish from infection-related fever 1
- Allergic reactions can occur due to streptokinase's bacterial-derived antigenic properties 6
- Pleural pain occurs in approximately 7% of patients 1
Important Clinical Context
However, streptokinase is no longer the preferred agent. The BTS/MRC Multicentre Intrapleural Streptokinase Trial demonstrated that streptokinase had no beneficial effect in adult empyema, and current British Thoracic Society guidelines recommend against its use due to lack of benefit and higher risk/benefit ratio compared to other fibrinolytics 6, 7.
The current preferred regimen is tPA 10 mg + DNase 5 mg twice daily for 3 days, which shows superior efficacy to streptokinase or either agent alone 7. If tPA/DNase is unavailable, urokinase 100,000 IU once daily for 3 days is the second-line choice 1, 8.
When to Escalate Care
- Discuss with thoracic surgeon if effective drainage not achieved by 5-8 day assessment point 1
- Do not continue fibrinolytic therapy indefinitely without reassessment—the standard 3-day course should prompt clinical evaluation 1
- Persistent fever, sepsis, or radiological collection despite treatment warrants surgical consultation 6
Practical Dosing Variations in Literature
While the standard dose is 250,000 IU twice daily, older studies used variable regimens:
- Some protocols used 250,000 IU once daily 4
- Number of instillations ranged from 2-10 doses depending on response 2, 3, 4
- Total cumulative doses up to 1.5 million IU have been studied without causing systemic fibrinolysis 6
The twice-daily dosing for 3 days represents the consensus guideline recommendation and provides a standardized approach for clinical practice 1.