title: Retrospective analysis of large-dose intrapleural alteplase for complicated pediatric parapneumonic effusion and empyema.
abstract: OBJECTIVE
  Medical treatment of complicated parapneumonic effusion or empyema in pediatric patients includes antibiotics and pleural space drainage. Intrapleural fibrinolysis may facilitate pleural drainage; however, there is a lack of consensus regarding the optimal dosing regimen. The primary purpose of this study was to evaluate the efficacy and safety of a large-dose intrapleural alteplase regimen in pediatric patients. Secondarily, this investigation sought to differentiate the clinical characteristics of responders and non-responders to intrapleural alteplase therapy.
  
  
  METHODS
  All patients with parapneumonic effusions treated with intrapleural alteplase between June 2003 and December 2011 were reviewed retrospectively. Efficacy was assessed by comparing chest tube output, in mL/hr and mL/kg/hr, for 24 hours before and after the first dose of alteplase. Additional efficacy outcomes included duration of in situ chest tubes, a need for surgical intervention for pleural effusion, and length of hospital stay. Safety was assessed by frequency and severity of adverse events. Non-responders and responders were compared based on demographic and disease characteristics. Responders were defined as patients who did not require surgical intervention after intrapleural alteplase therapy.
  
  
  RESULTS
  Seventy-three patients, aged 0.5 to 22.5 years, received intrapleural alteplase to facilitate pleural drainage. Median alteplase dose was 7 mg (range, 3 to 10 mg; median 0.38 mg/kg). Chest tube output increased from 10.7 to 24.2 mL/hr (p = 0.006), and median length of hospital stay was 9 days. Eighty-four percent of patients were responders. The most common adverse events were pain (20.5%) and oxygen desaturation greater than 10% from baseline (16.4%). High-flow nasal cannula was the most common intervention for oxygen desaturation to 80% to 90%. Nine patients (12%) required a blood transfusion during the study.
  
  
  CONCLUSIONS
  Large-dose intrapleural alteplase is effective in facilitating pleural drainage in pediatric patients with complicated parapneumonic effusion or empyema. Common adverse effects include pain and oxygen desaturation. The potential for bleeding warrants clinical monitoring.
authors.affiliation: Department of Pharmacy, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Taylor
authors.affiliation: Department of Healthcare Economics, Medica, Hopkins, Minnesota.
authors.forename: Meixia
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota.
authors.forename: David S
authors.initials: DS
authors.lastname: Hoff
keywords: empyema; pediatrics; pleural effusion; pneumonia; tissue plasminogen activator