Intrapleural Fibrinolytic Therapy Research Articles

Management of Parapneumonic Effusions:Current Practice and Controversies

The incidence of complicated parapneumonic effusions in children has been increasing over the past decade despite the increasing use of protein-conjugate vaccines against Streptococcus pneumoniae, the most common cause of complicated pneumonia in children in the developed world. Despite the fact that this condition is increasingly common in hospitalized children, the management of this condition remains controversial, in large part due to the small number of prospective, controlled trials evaluating therapies. This review will highlight the epidemiology, diagnosis and management of complicated parapneumonic effusions. The role for intrapleural fibrinolytic therapy and early videoassisted thorascopic surgery in the management of this condition will be emphasized as will the questions that need to be answered with future inquiry.

Intrapleural Fibrinolytic Agents for Empyema and Complicated Parapneumonic Effusions: A Meta-analysis

Randomized controlled trials have shown conflicting findings about the role of intrapleural fibrinolytic therapy for the treatment of empyema and complicated parapneumonic effusions in adult patients. To assess the clinical efficacy and summarize the current evidence of intrapleural fibrinolytic use in patients with empyema and complicated parapneumonic effusions in adult patients. We performed a meta-analysis of all properly randomized trials comparing intrapleural fibrinolytic agents with placebo in adult patients with empyema and complicated parapneumonic effusions. Outcome of primary interest was the reduction of death and surgical intervention. We included five trials totaling 575 patients. The number of enrolled patients for each trial was small, except for the recent trial by Multicenter Intrapleural Sepsis Trial (MIST1) group. Compared with placebo, intrapleural fibrinolytic therapy was associated with a nonsignificant reduction in death and need for surgery (27.6% of the treatment group vs 32.8% of the control group; random-effects pooled risk ratio, 0.55; 95% confidence interval, 0.28 to 1.07; heterogeneity, p = 0.023). A separate analysis for outcomes on either death or need for surgery also showed nonsignificant results. Our meta-analysis does not support the routine use of fibrinolytic therapy for all patients who require chest tube drainage for empyema or complicated parapneumonic effusions. However, there was significant heterogeneity of the treatment effects among the trials. Selected patients might benefit from the treatment.

Die Behandlung des parapneumonischen Ergusses und des Pleuraempyems

Pleural effusions of infectious origin usually present as a complication of pneumonia, or, more rarely, of thoracic surgical procedures. Treatment is based upon the clinical picture, the appearance of the pleural fluid, on certain laboratory parameters, and upon the success of therapeutic interventions. The initial antibiotic regimen should cover the causative organisms that may empirically be expected in the individual setting of the patient. Similar to the situation in pneumonias, the spectrum of organisms in community-acquired effusions or empyemas differs substantially from that in hospital-acquired pleural infections. The management of pleural empyemas should follow an interdisciplinary strategy which involves the pulmonologist and the thoracic surgeon. The single most important intervention is the early and effective drainage of the pleural cavity. Loculated effusions that do not promptly improve after drainage can additionally be treated by a trial of intrapleural fibrinolysis for a period of approximately three days. However, the precise role of fibrinolytics in the setting of complicated pleural effusions and empyemas remains to be better defined. Early definitive surgical treatment, preferentially by video-assisted thoracoscopic surgery (VATS), should be the goal in all patients who do not promptly respond to drainage and/or intrapleural fibrinolytic therapy and who qualify for a surgical intervention.

Practice of early-stage fibrinolytic therapy at postoperative clotted hemothorax

Summary A 27-year-old male patient with diagnosis of first-episode pneumothorax was admitted to our clinic. Tube thoracostomy was performed and the chest tube was removed after lung expansion. Pneumothorax was repeated in the first day after removing the chest tube. Then, apical pleurectomy was performed by video-assisted thorocoscopic surgery. Postoperative clotted hemothorax developed after pleurectomy operation. Effective drainage was provided by intrapleural fibrinolytic therapy with streptokinase on the postoperative first day.

Management of postpneumonic empyemas in children.

Despite continued improvement in medical therapy, pediatric empyema remains a challenging problem for the surgeon. Multiple treatment options are available; however, the optimal therapeutic management has not been elucidated. The aim of this study is to assess different treatment options in the management of postpneumonic pediatric empyemas. A retrospective review was performed of pediatric patients admitted to Dicle University School of Medicine Thoracic and Cardiovascular Surgery Department between 1990 and 2002, with the diagnosis of empyema. Data tabulated included patient demographics, presentation, treatment and outcome. There were 515 children (289 boys and 226 girls) with a mean age of 4.7 ranging from 18 days to 15 years. Empyema was secondary to pneumonia in all children. The most common radiologic finding was pleural effusion in 285 patients (55.32%). Staphylococcus aureus was the most frequently encountered organism and found in 105 patients (20.38%). Pleural fluid cultures were negative in 195 patients (37.86%). In addition to antibiotic therapy, initial treatment included serial thoracenthesis (n = 29), chest tube drainage alone (n = 214), chest tube drainage with intrapleural fibrinolytic therapy (n = 72), chest tube drainage with primary operation (n = 191), and primary operation without chest tube drainage (n = 9). Overall response rate with fibrinolytic treatment (complete and partial response) was obtained in 58 patients. In addition to decortication pulmonary resections were performed in 12 patients. Overall mortality rate was 1.55%. There was no operative mortality. Postoperative morbidity included wound infection in 21, delayed expansion in 8, and atelectasis in 35 patients. Multiple therapeutic options are available for the management of pediatric empyema. Depending on stages, every option has a role in the treatment of postpneumonic pediatric empyema. In the absence of bronchopleural fistula, intrapleural fibrinolytic treatment should be tried in all patients with multiloculations in stage II empyema. In the absence of pneumonia, decortication for empyema is a safe approach with low mortality and morbidity rates.

Management of parapneumonic effusion and empyema

Aims: To gather data on the clinical presentation of parapneumonic effusion and empyema and to examine the effect of different management strategies on short term outcomes. Methods: Retrospective case note...

Pleural fluids associated with chest infection

Pleural effusions are commonly associated with pneumonias and a small number of these progress to empyema. An understanding of the physiology and pathophysiology of pleural fluid aids the clinician in the management of empyema. There remains much debate about the optimal treatment of empyema in children. Early recognition of the condition is important since delayed therapy may result in unnecessary morbidity. Conventional management with high dose parenteral antibiotics and chest tube drainage remains the mainstay of therapy. However, this treatment modality may fail if the pleural fluid becomes viscous and loculated and, therefore, a more aggressive approach is required. Intrapleural fibrinolytic therapy has been shown to decrease the length of hospital stay and may reduce the need for surgical intervention. The prognosis in children with parapneumonic empyema is excellent with the vast majority retaining normal lung function at long term follow-up.

Management of parapneumonic pleural effusion.

Parapneumonic pleural effusion is a common and potentially serious complication of pneumonia. The management of parapneumonic pleural effusion involves early diagnosis, adequate empiric antibiotic cover, and appropriate risk categorization. High-risk patients require safe and expedient drainage of the infected pleural space. The management options include thoracentesis, tube thoracostomy, adjunctive intrapleural fibrinolytic therapy, and surgical drainage. The methods of surgical drainage include thoracoscopy, thoracotomy, and decortication. The relative clinical efficacy of these treatment options has been studied in a small number of controlled clinical trials, the results of which have been systematically reviewed by expert panels. Based on the limited clinical evidence, expert reviewers were unable to recommend a best method of pleural drainage. However, the consensus is that an aggressive approach with early surgical drainage results in shorter hospital stays and may be more cost-effective than conservative management. This review discusses the clinical evidence and describes an aggressive sequential management strategy that combines intrapleural fibrinolysis with early surgical drainage.

Sonographic septation: a useful prognostic indicator of acute thoracic empyema.

The aim of this study was to identify sonographic predictors of patient outcomes or need for surgical intervention of acute thoracic empyema. All patients with a clinical diagnosis of thoracic empyema underwent transthoracic ultrasonographic examination and thoracentesis at admission. According to the presence or absence of septa in sonographic images, the patients were classified into two groups: septated and nonseptated. Sonographic findings were analyzed with respect to duration of hospital stay, chest tube drainage, and treatment efficacy. A total of 163 consecutive patients were included in the study (83 patients with septated and 80 with nonseptated sonographic images). The mean duration of hospital stay (35.4 versus 27.0 days, P = 0.009) and chest tube drainage (13.1 versus 7.6 days, P < 0.001) for the patients with septa were significantly longer than for those without septa. The patients with septa were more likely to undergo intrapleural fibrinolytic therapy (63.8% versus 38.8%, odds ratio 2.79, P = 0.001) and surgical intervention (24.3% versus 7.5%, odds ratio 3.92, P = 0.004). We concluded that sonographic septation is a useful sign to predict the need for subsequent intrapleural fibrinolytic therapy and surgical intervention in cases of acute thoracic empyema. Early fibrinolytic therapy or even surgical intervention may be indicated in patients with sonographic septations.

Optimal management of complicated empyema

Background: Despite continued improvement in medical therapy, empyema remains a challenging problem for the surgeon. Multiple treatment options are available; however, the optimal therapeutic management has not been elucidated. Methods: A retrospective review was performed of all adult patients admitted to Denver Health Medical Center between January 1, 1993, and December 31, 1998, with the diagnosis of empyema. Data tabulated included patient demographics, presentation, chest computed tomography (CT) findings, treatment, and outcome. Results: Empyema was diagnosed in 58 patients, 45 cases of which were multiloculated at the time of presentation. Empyema was secondary to pneumonia is 41 patients and posttraumatic in 15. In addition to antibiotic therapy, initial treatment included chest tube drainage alone (n = 6), chest tube drainage with primary operation (n = 19), and chest tube drainage with intrapleural fibrinolytic therapy (n = 33). In 15 patients (45%), fibrinolytic therapy failed. Initial chest CT revealed a pleural peel in 5 patients treated with fibrinolytics and all failed. Multiloculation, however, was not a factor in failure of fibrinolysis. Moreover, chest CT missed the presence of a pleural peel in 17 of 31 patients documented to have a significant peel at the time of thoracotomy. Conclusion: Multiple therapeutic options are available for the management of empyema. Multiloculation is not a contraindication to an initial trial of chest tube drainage or fibrinolytic therapy. In contrast, CT evidence of a pleural peel uniformly predicted failure of nonoperative treatment.

Intra-pleural fibrinolytic therapy vs. conservative management in the treatment of parapneumonic effusions and empyema.

Effusions and empyema may complicate lower respiratory tract infections. Loculation of fluid is a major problem with this condition so treatments have included surgical drainage and the use of intra-pulmonary fibrinolysis to break down fibrin bands that may cause loculation. To conduct a systematic review of the benefit of adding intrapleural fibrinolytic therapy to intercostal tube drainage in the treatment of complicated parapneumonic effusions and empyema. The Cochrane Controlled Trials Register was initially searched for relevant RCT's. The search terms were Streptokinase OR Urokinase AND Pleural Effusion OR Intrapleural OR Pleur* OR Parapneumonic Or Empyema. Bibliographies and review articles identified herein were searched for further citations and RCT's. MEDLINE, EMBASE were searched and, where relevant, Index Medicus was hand searched. Trial authors were contacted for further information and details regarding the possibility of unpublished trials was requested. Types of Studies All studies in the review were Randomised Controlled Trials in adult patients empyema or complicated parapneumonic effusions who had not had prior surgical intervention or trauma. The intervention was an intrapleural fibrinolytic agent (streptokinase or urokinase) vs control or a comparison of the two. All identified studies were reviewed independently by two reviewer and all data collected. Reviews were scored according to the Cochrane assessment of allocation concealment and the Jadad scale of methodological quality. Disagreements between reviewers were referred to a third reviewer. Where further information was required, authors of trial papers were contacted for further details. Three studies were identified, one which directly compared the fibrinolytics streptokinase and urokinase. Two small RCTs (total 58 patients) compared streptokinase or urokinase vs normal saline control. The pooled data showed small benefits in terms of hospital stay, time to defervescence, improvement in chest radiograph, requirement for surgery, but the results were not always consistent across studies. Complications attributable to therapy were not seen. There is currently insufficient evidence to support routine use of intrapleural fibrinolytic therapy in the treatment of parapneumonic effusion and empyema. The results of a large multi-centre study, currently underway, are awaited.

Intrapleural fibrinolytic therapy for complicated pleural effusions

Intrapleural administration of fibrinolytic agents can be used to degrade the fibrin present in complicated pleural effusions, thus decreasing viscosity of the fluid and enhancing evacuation of the pleural space via chest tube drainage. Patients who may otherwise need surgical intervention could benefit from this treatment. As more knowledge is gained through clinical experience and research studies, patients' outcomes may show major improvement.

Posttraumatic empyema thoracis: a 24-year experience at a major trauma center.

The purpose of this paper is to review the outcome of patients with posttraumatic empyema thoracis. Between April 1972 and March 1996, the Division of Cardiothoracic Surgery at the King-Drew Medical Center managed or was consulted on 5,474 trauma patients (4,584 patients with penetrating injuries and 890 with blunt injuries) who were admitted emergently for thoracic and thoracoabdominal injuries and who underwent tube thoracostomy. Patients were not given routine prophylactic antibiotics merely because they had a chest tube placed. Based on our previous reports on thoracic trauma, our criteria for empiric antibiotic administration included (1) emergent or urgent thoracotomy, (2) soft-tissue destruction of the chest wall by shotgun injuries, (3) lung contusion with hemoptysis, (4) associated abdominal trauma requiring exploratory laparotomy, or (5) associated open long-bone fractures. Eighty-seven of these 5,474 patients developed posttraumatic empyema thoracis, for an incidence of 1.6%. These 87 patients were treated with tube thoracostomy, image-guided catheter drainage, or open thoracotomy with decortication. Seventy-nine of 87 patients (91%) were cured without conversion to open thoracostomy. Four patients required conversion to open thoracostomy, and there were three deaths. Even though a majority of our patients required decortication, successful management of posttraumatic empyema thoracis also was achieved with closed-tube thoracostomy or image-guided catheter drainage based on clinical and radiographic findings with appropriate patient selection. When thoracic empyema did occur in our group, Staphylococcus aureus was the most common microbe isolated, followed by anaerobic bacteria. In correlating microbiologic data with outcomes, S. aureus, especially methicillin-resistant S. aureus, was the most frequent cause of antibiotic failure. Because of the low incidence of posttraumatic empyema thoracis, we do not recommend routine antibiotic prophylaxis for all trauma patients who undergo closed-tube thoracostomy. A review of the role of tube thoracostomy, intrapleural fibrinolytic therapy, image-guided catheter drainage, video-assisted thoracoscopy, and open thoracotomy for the management of thoracic empyema is provided.

Intrapleural Fibrinolysis With Streptokinase as an Adjunctive Treatment in Hemothorax and Empyema: A Multicenter Trial

To test the efficacy of intrapleural fibrinolytic therapy in patients with loculated pleural effusions, we conducted an open, prospective, and multicenter trial among five hospitals in Mexico. We enrolled patients with hemothorax or empyema, clotted and/or loculated, that was not resolved through conventional pleural drainage with chest tube and antibiotics in patients with empyema. All patients received repeated doses of 250,000 IU of streptokinase through chest tube. Effectiveness criteria were before and after intrapleural streptokinase (IPSK) drainage, and poststreptokinase radiographic and respiratory function test improvement. Forty-eight patients were studied; there were 30 patients with empyemas, 14 with hemothorax, and 4 patients with malignant pleural effusions without lung trapping. Successful fibrinolysis was obtained in 44 patients, with complete resolution of the pleural collection and adequate radiologic and spirometric improvement. In three of four patients with multiloculated malignant hemothorax with high-yielding pleural drainage, IPSK allowed successful lysis of loci and an adequate pleurodesis was achieved. Only four patients required surgical treatment. The overall success rate in our series was 92%, similar to previous reports. The results in this first prospective and multicentric trial suggest that intrapleural fibrinolysis is an effective and safe adjunctive treatment in patients with heterogeneous pleural coagulated and loculated collections to restore the pulmonary function assessed by respiratory function tests and can obviate surgery in most cases.

Profiles of local fibrinolytic activity before and after urokinase injection into the human empyema cavity.

Background: In recent reports, it has been reported that increased coagulation and decreased fibrinolytic activity has been responsible for abnormal fibrin turnover in exudative pleural effusion. In the cases of empyema, the fibrinopurulent stage is characterized by the fibrin deposition resulting in formation of limiting membranes in the visceral and parietal pleura. Recently attention has been focused on intrapleural fibrinolytic therapy capable of removing intrapleural fibrin deposits by urokinase (UK) in the treatment of empyema. However, these clinical trials have provided the clinical evidences for resolution of pleural loculation after intrapleural urokinase injection (UK-injection), the profiles of fibrinolytic activity following the treatment were still not investigated. Therefore in order to demonstrate the fibrinolytic evidences behind the clinical efficacy of intracavitary UK-injection, we examined intrapleural plasminogen activator activity (PA-activity) and D-dimer (D-Di) concentrations before and after each repeated UK-injection into the pleura in subjects with loculated empyema cavity. Methods: In a group of 14 patients with multiple loculated empyema cavity, PA-activity and D-Di concentrations were measured before and after repeated UK-injection. One hundred thousand IU of UK was injected at each time and all sujects had at least two times of UK injection accoring to clinical decisions. Nine out of 14 sujects had three times of UK-injection. Results: The mean () PA-activity prior to treatemnt was and it was increased to IU tPA/ml after first, second and third time of UK-injection respectively (p to ng/ml in the same order as above (p