Related Experiment Video
Updated: Dec 29, 2025
Author Spotlight: A Non-Intubated Video-Assisted Thoracoscopic Surgery with Multimodal Analgesia and Sevoflurane Inhalation Anesthesia
Published on: May 26, 2023
Effectiveness of Intrapleural Tissue Plasminogen Activator and Dornase Alfa vs Tissue Plasminogen Activator Alone in
Michael H Livingston1,2, Sanjay Mahant3, Bairbre Connolly4
1McMaster Children's Hospital, McMaster University, Hamilton, Ontario, Canada.
Insights
Adding dornase alfa (DNase) to tissue plasminogen activator (tPA) did not reduce hospital stays for pediatric pleural empyema. Current guidelines recommending chest tubes and fibrinolytics alone remain appropriate for children.
Area of Science:
- Pediatric Pulmonology
- Thoracic Surgery
- Critical Care Medicine
Background:
- Clinical guidelines advocate chest tube insertion and intrapleural fibrinolytics for pediatric pleural empyema.
- Dornase alfa (DNase) shows promise in adults but its efficacy in children with pleural empyema is unproven.
Purpose of the Study:
- To evaluate if intrapleural tissue plasminogen activator (tPA) combined with DNase is more effective than tPA with placebo in reducing hospital length of stay for pediatric pleural empyema.
Main Methods:
- A multicenter, randomized, placebo-controlled trial involving 97 children (6 months to 18 years) with pleural empyema.
- Participants received intrapleural tPA with either DNase (intervention) or saline placebo (control) for 3 days post-chest tube insertion.
- The primary outcome was hospital length of stay; secondary outcomes included time to discharge criteria, chest tube removal, fever duration, and healthcare costs.
Main Results:
- No significant difference in hospital length of stay was found between the tPA and DNase group (9.0 days) and the tPA and placebo group (9.1 days).
- Secondary outcomes, including time to discharge, chest tube removal, and fever duration, also showed no significant differences between groups.
- Adverse events occurred in both groups, with no deaths reported.
Conclusions:
- The addition of DNase to intrapleural tPA does not improve outcomes for children with pleural empyema.
- Current clinical practice guidelines recommending chest tube insertion and intrapleural fibrinolytics as first-line treatment for pediatric empyema should be maintained.
Importance:
Clinical guidelines recommend that children with pleural empyema be treated with chest tube insertion and intrapleural fibrinolytics. The addition of dornase alfa (DNase) has been reported to improve outcomes in adults but remains unproven in children.
Objective:
To determine if intrapleural tissue plasminogen activator (tPA) and DNase is more effective than tPA and placebo at reducing hospital length of stay in children with pleural empyema.
Design, Setting, And Participants:
This multicenter, parallel-group, placebo-controlled, superiority randomized clinical trial included children diagnosed as having pleural empyema requiring drainage aged 6 months to 18 years treated at 6 tertiary Canadian children's hospitals. A total of 379 children were assessed for eligibility; 281 were excluded and 98 were randomized. One child was excluded after randomization for not meeting the inclusion criteria. Data were collected from March 4, 2013, to December 13, 2017.
Interventions:
Participants underwent chest tube insertion and 3 daily administrations of intrapleural tPA, 4 mg, followed by DNase, 5 mg (intervention group), or 5 mL of normal saline (placebo; control group). Participants, families, clinical staff, and members of the study team were blinded to allocation.
Main Outcomes And Measures:
The primary outcome was hospital length of stay from chest tube insertion to discharge. Secondary outcomes included time to meeting discharge criteria, time to chest tube removal, mean fever duration, additional pleural drainage procedures, hospital readmissions, and total health care cost.
Results:
Of the 97 analyzed children with pleural empyema, 52 (54%) were male, and the mean (SD) age was 5.1 (3.6) years. A total of 49 children were randomized to tPA and DNase and 48 were randomized to tPA and placebo. Treatment with tPA and DNase was not associated with decreased hospital length of stay compared with tPA and placebo (mean [SD] length of stay, 9.0 [4.9] vs 9.1 [5.3] days; mean difference, -0.1 days; 95% CI, -2.0 to 2.1; P = .96). Similarly, no significant differences were observed for any of the secondary outcomes. Of the 14 adverse events in the tPA and DNase group, 6 (43%) were serious; of the 21 adverse events in the tPA and placebo group, 8 (38%) were serious. There were no deaths.
Conclusions And Relevance:
The addition of DNase to intrapleural tPA for children with pleural empyema had no effect on hospital length of stay or other outcomes compared with tPA with placebo. Clinical practice guidelines should continue to support the use of chest tube insertion and intrapleural fibrinolytics alone as first-line treatment for pediatric empyema.
Trial Registration:
ClinicalTrials.gov identifier: NCT01717742.
Related Concept Videos
01:29Pulmonary Embolism II: Diagnostic Studies and Interprofessional Care
01:27Pulmonary Embolism III: Nursing Management
01:26Flail Chest-II
Assessment:
1. Clinical Evaluation:
History: