| Abstract |
Pneumonia is associated with a 36 to 57% incidence of pleural effusions. The spectrum of pleural effusions associated with bacterial pneumonias includes simple parapneumonic pleural effusions (PPE) (exudative, stage I), complicated PPE (CPE) (fibropurulent, stage II), and pleural empyema (organization, stage III). The last two entities are associated with substantial morbidity and mortality. The most serious complication is frank empyema, leading to sepsis, disseminated abscesses, and death in 8 to 33% of the cases. The best methods for treating CPE and pleural empyemas remain debatable because of the lack of prospective, randomized trials. The availability of new option for management further confounds clinical decision making. Although traditional surgical options (simple tube thoracostomy, rib resection, decortication, and thoracoplasty) are effective, any treatment that reduces the number of surgical interventions is preferred. The scope of the study was to investigate the efficacy, safety and cost of intrapleural administration of fibrinolytics (streptokinase and urokinase), used as an adjunct to chest tube drainage in the management of CPE and pleural empyema, compares the two fibrinolytics and compare the intrapleural instillation of urokinase and normal saline, in a radomized, prospective, double-blind fashion in terms of effectiveness and role of the instilled volume. Therefore we design 4 protocolls with the same inclusion and exclusion criteria and the same method for assesment. Patients and Methods Protocol No 1: Twenty consecutive patients (15 CPE, 5 empyemas) received streptokinase (SK) intrapleurally in a single daily dose of 250,000 IU in 100 ml normal saline via the chest tube once the drainage was <100 ml/24h. The chest tube was clamped for 3h after instillation. Protocol No 2: Twenty consecutive patients (13 CPE, 7 empyemas), in whom a single chest tube failed to drain the fluid were studied prospectively. Urokinase (UK) was administered intrapleurally, in a low single daily dose of 50,000 IU in 100 ml normal saline via the chest tube. The chest tube was clamped for 3h after instillation. Protocol No 3: Fifty consecutive patients with CPE or empyemas were randomly allocated to receive either SK (25 patients) or UK, in a double-blind fashion. All patients had inadequate drainage through chest tube (<70 ml/24h). Both drugs were diluted in 100 ml normal saline and were infused intrapleurally through the chest tube in a daily dose of 250,000 IU of SK or 100,000 IU of UK. The chest tube was clamped for 3h after instillation. Protocol No 4: Thirty-one consecutive patients with CPE or empyemas were randomly assigned to receive either UK (15 patients) or normal saline (16 patients) for three days, in a double-blind fashion. All patients had inadequate drainage through chest tube (<70 ml/24h). Urokinase was given daily through the chest tube in a dose of 100,000 IU diluted in 100 ml normal saline. Controls were given intrapleurally the same volume of normal saline. Results Protocol No 1: Following administration of SK a clinical and radiological improvement was noted in all but one patient (19/20). A significant increase in drainage was seen at 24 and 72h after SK administration compared with the volume before SK (p<0.01). The number of SK instillations ranged 3-10 (median 6). One patient developed a high fever as an adverse reaction to SK. The overall succes rate was 95%. Protocol No 2: Urokinase enhanced drainage in all patients. Clinical and radiological improvement was noted in all but one patient (19/20). The mean (SD) volume of fluid significantly increased in the first 24h post-UK (p<0.001). The number of UK instillations ranged 3-7 (median 5). The overall succes rate was 95%. Protocol No 3: Clinical and radiological improvement was noted in all but two patients in each group, who required surgical intervention. A significant increase in the mean daily pleural fluid drainage was seen after either drug administration compared with the drained volume 24h before treatment (p<0.01). High fever as an adverse reaction to SK was observed in two patients. The cost of UK was relatively little higher than that of SK. Protocol No 4: Pleural fluid drainage was complete in 13 (86.5%) patients in the UK group (two patients submitted to video-assisted thoracoscopy) and only in 4 (25%) in the control group. Twelve patients of the control group were subsequently treated with UK and 6 of them had a complete drainage; the remaining 6 patients had a complete drainage after video-assisted thoracoscopy. Conclusions Intrapleural fibrinolytics (SK or UK) is an safe and effective adjunt in the management of parapneumonic effusions and may reduse the need for surgery. Fibrinolytics is effective in the treatment of CPE and empyemas through the lysis of the pleural adhesions and not due to volume effect. Urokinase could be the fibrinolytic of choise given the potentially dangerous allergic reactions to SK and relatively little higher cost of UK.
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