Clinical Response-Guided tPA and DNase Administration as Rescue Treatment for Postoperative Empyema

Abstract

Empyema untreated carries significant mortality. Medical management with tube thoracostomy accompanied by combination therapy with intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNase, dornase alpha) has decreased the need for surgical intervention. Most studies on this combination therapy have been done on empyema associated with community acquired pneumonia. A fixed regimen of tPA and DNase has a high cost and carries a small risk of intrapleural hemorrhage. We report on two patients who developed empyema postoperatively. Intrapleural DNase and tPA were administered concurrently at a frequency and duration based upon the clinical response. Both patients had successful outcomes without adverse effects. Interna tional Society of Pl eural Dis eas es Resc ue Intervention in Late Postopera tive Empyema 2 INTRODUCTION The incidence of empyema is increasing worldwide. Untreated, empyema carries a 20% mortality. 1-4 Primary management involves antibiotics and tube thoracostomy. Empyema with increased pleural fluid viscosity and the presence of loculations may be refractory to this approach. Refractory empyema is treated with surgical decortication and drainage, an approach associated with increased hospitalization. An alternative to surgery is tube thoracostomy followed by the administration of intrapleural tPA and DNase twice a day for three days. tPA, through the generation of plasmin, * helps to breakdown loculations. DNase decreases pleural fluid viscosity by digesting free deoxyribonucleoprotein from leukocyte degradation. TPA and DNase are expensive and may cause adverse effects, notably intrapleural hemorrhage. Administration of either one of these drugs alone has not been shown to be beneficial. 5,6 Observational studies have shown that the administration of this combination therapy according to clinical response does not change efficacy. There are no specific studies addressing tPA / DNase treatment of empyema which formed in the late postoperative period. We report two postoperative empyema cases treated successfully with late administration (after over 48 hours of chest tube drainage) with intrapleural combination therapy. * tPA converts plasminogen to plasmin, a member of the serine protease family (which includes trypsin). Plasmin proteolyzes numerous proteins including fibrin and fibronectin. It also activates collagenases. Case 1 A 68 year old woman with alcohol abuse and a 12 pack-year history of cigarette smoking was found to have a spiculated 1.4 cm right upper lobe nodule. She underwent elective video assisted thoracoscopy for a right upper lobe wedge resection. Her hospitalization was complicated by alcohol withdrawal, prolonged mechanical ventilation requiring a tracheostomy, acute blood loss from tracheal erosion, and acute kidney injury requiring hemodialysis. On postoperative day thirty, she was noted to have increasing right-sided consolidation, a pleural effusion, and persistent leukocytosis. Figure 1. Initial chest radiograph of the showing the left-sided loculated pleural effusion. A pigtail catheter (14 Fr) was placed. Pleural fluid studies showed cloudy fluid, glucose < 10 mg/dL, LDH 11,119 U/L, total protein < 3 g/dL, pH 6.9, WBC 300,000 cells/μL, RBC 101,000 cells/μL, neutrophils 95%, cholesterol 78 mg/dL, and amylase 36 mg/dL. Piperacillintazobactam and vancomycin were administered. After 48 hours, the chest tube drainage decreased from 800 mL to 150 mL/24 hours. There was no radiographic improvement of the pleural effusion. Due to hemodynamic instability, the patient was at high risk for surgery. This prompted treatment with intrapleural tPA 10 mg and DNase 5 mg administered together. The drainage increased from 150 mL to 570 mL per 24 hours. After four days, the drainage deInterna tional Society of Pl eural Dis eas es Resc ue Intervention in Late Postopera tive Empyema 3 creased to 120 mL per day. A second dose of tPA 10 mg and DNase 5 mg was given. The chest tube drainage increased to 300 mL per day. The pleural fluid culture was positive for Gemella morbillorum. Her antibiotic regimen was changed to cefoxitin. Figure 2. Radiograph of the chest showing almost complete resolution of the pleural effusion after drainage, antibiotics, and rescue administration of intrapleural tPA and DNase. The pleural drainage subsequently diminished and there was radiographic improvement of the pleural effusion. The pleural drainage transitioned from frank pus to serosanguinous fluid. The chest tube was removed after 10 days. The patient was discharged to long term acute care (LTAC).