Approval was obtained from the Children’s Mercy Hospital (Kansas City, Mo) Institutional Review Board (IRB) before enrolling patients in this study (IRB no. 06 01-019). Patients were subsequently enrolled only after obtaining consent from the patient’s legal guardian. The consent forms and consent process were carefully evaluated by the IRB on a continual basis. The trial was registered with clinicaltrials.gov
(ID: NCT00323531). All persons obtaining consent participated in specific IRB training in the consent process.
The study population consisted of patients younger than 18 years with a diagnosis of empyema.
Inclusion criteria required the diagnosis of empyema. Empyema was defined as septations or loculations identified in the pleural space by computed tomography or ultrasound. In addition, patients with a frankly purulent tap with white blood cell count greater than 10,000 cells/μL were included.
Exclusion criteria were an existing contraindication to either thoracoscopy or to the fibrinolytic agent. In addition, patients with additional foci of infection or a diagnosis of an immunocompromised state were excluded. Patients with comorbid conditions that would require hospitalization beyond the course of the empyema were excluded.
After diagnosis, patients were randomized to treatment by either video-assisted thoracoscopic debridement or pleural infusion of fibrinolytic solution. The fibrinolytic agent was Activase (alteplase; Genentech Inc, San Francisco, Calif), which is a recombinant version of human tissue plasminogen activator (tPA).
1.3. Sample size
Power calculation was based on length of hospitalization obtained from retrospective data within our institution between patients treated with fibrinolysis and those treated with thoracoscopy. Establishing α at .05 and a power of 0.80, this produced a sample size of 18 patients per arm.
The randomization sequence was computer generated using an individual unit of randomization in an unstratified sequence in blocks of 4. After empyema was diagnosed as described above, the family was approached for informed permission for the patient to participate by one of the named authors of this study. The randomization sequence was accessed to identify the next allotment after the consent form was signed.
Thoracoscopic debridement was performed by 1 of 5 institutional staff surgeons with thoracoscopic experience as dictated by the call schedule. The number and size of ports used were dictated by the patient size and difficulty of debridement. In general, 3 ports were used using one 10-mm port and two 5-mm ports. The initial fluid and/or pieces of the solid debris were sent for culture. In all cases, a single soft suction drain in the form of a 19F round Blake drain (Ethicon Inc, Piscataway, NJ) was left to drain the pleural space.
Patients treated with fibrinolysis had a 12F chest tube placed using the Seldinger technique (Thal-Quick Chest Tubes, Cook Critical Care, Bloomington, Ind). The small size of chest tubes was chosen on the basis that larger drains have been shown to confer no advantage in empyema treatment when fibrinolysis is used [23
]. Tubes were placed using local anesthetic with sedation either at the bedside, in a dedicated procedure room, or in the operating room depending on the age of the patient, physiologic status, time of day, and staff available for sedation. The initial drainage fluid was sent for culture, and the tubes were then placed on continuous suction at a pressure of −20 cm H2
0. Fibrinolysis was performed by mixing 4 mg of tPA into 40 mL of sterile normal saline on the floor by the administering physician. This solution was injected directly into the tube with a dwell time of 1 hour after which the tube was placed back to continuous suction. The tPA solution was administered at the time of tube placement with 2 additional doses each given 24 hours later to comprise 3 treatments for a 48-hour span.
Tubes in both arms were managed by the surgical service, and they were removed when there was no sign of air leakage and drainage output was less than 1 mL/kg per day calculated for the previous 12 hours.
After intervention, discharge criteria consisted of the patient remaining afebrile for 48 hours, tolerating regular diet, and off oxygen therapy. Patients were discharged to home with a minimum 10-day course of oral antibiotics that offered comparable antimicrobial coverage as the intravenous regimen at the time of discharge.
The general antimicrobial plan for both groups consisted of clindamycin (10 mg/kg per dose) every 6 hours and ceftriaxone (25 mg/kg per dose) every 12 hours. If hemodynamic instability existed (hypotension, need for vasoactive medications, or persistent tachycardia), then vancomycin (15 mg/kg per dose) every 6 hours was added. Antibiotic therapy was tailored toward positive culture results and the individual patient’s course. All patients were observed by the infectious disease team who directed outpatient therapy and follow-up.
1.6. Data collection
Upon diagnosis, age, weight, degree of oxygen support, white blood cell count, days of symptoms before diagnosis, and number of doctor visits before intervention were recorded. Results from pleural and blood cultures were recorded.
After the intervention, length of hospitalization, days and degree of oxygen therapy, days until afebrile, analgesic doses, requirements for a second procedure, and patient charges were recorded. All complications, readmissions, and recurrences were recorded. Procedure charges were compiled from procedures used for the treatment of the empyema only. This includes both fibrinolysis and the subsequent operation for the fibrinolysis patients who did not respond. General hospital charges including intensive care support measures were not included in the procedure charges.
1.7. Statistical analysis
Continuous variables were compared using an independent sample, 2-tailed Student’s t test. Discrete variables were analyzed with Fisher’s Exact test. Significance was defined as P value of .05 or less. Descriptive statistics are listed at mean ± SD.