Intrapleural Fibrinolytic Therapy Research Articles

Management of Pleural Infection: A Historical Review and Updates

Pleural infection, including empyema, continues to have a high morbidity. A deep understanding of the pathobiology and appropriate medical management is crucial to avoid complications and progression to the need for surgery. Over the last several decades, we have learned much about the pathophysiology, microbiology, and epidemiology of pleural infections. Management has changed considerably over the years with more recent clinical practices favoring minimally invasive interventions over surgery. Here we discuss in detail the pathophysiology of parapneumonic effusions as they progress from uncomplicated parapneumonic effusions to empyema and how this relates to their diagnosis and management. We review the microbiology and how it relates to recommended empiric antibiotic regimens. As intrapleural fibrinolytic therapy has become the cornerstone of management, we outline the literature on this topic dating back decades up to the most recent clinical trials and give our recommendations for management based on the literature.

Outcomes of Pleural Space Infections in Patients With Indwelling Pleural Catheters for Active Malignancies.

Pleural infections related to indwelling pleural catheters (IPCs) are an uncommon clinical problem. However, management decisions can be complex for patients with active malignancies due to their comorbidities and limited life expectancies. There are limited studies on the management of IPC-related infections, including whether to remove the IPC or use intrapleural fibrinolytics. We conducted a retrospective cohort study of patients with active malignancies and IPC-related empyemas at our institution between January 1, 2005 and May 31, 2021. The primary outcome was to evaluate clinical outcomes in patients with malignant pleural effusions and IPC-related empyemas treated with intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) compared with those treated with tPA alone or no intrapleural fibrinolytic therapy. The secondary outcome evaluated was the incidence of bleeding complications. We identified 69 patients with a malignant pleural effusion and an IPC-related empyema. Twenty patients received tPA/DNase, 9 received tPA alone, and 40 were managed without fibrinolytics. Those treated with fibrinolytics were more likely to have their IPCs removed as part of the initial management strategy ( P =0.004). The rate of surgical intervention and mortality attributable to the empyema were not significantly different between treatment groups. There were no bleeding events in any group. In patients with IPC-related empyemas, we did not find significant differences in the rates of surgical intervention, empyema-related mortality, or bleeding complications in those treated with intrapleural tPA/DNase, tPA alone, or no fibrinolytics. More patients who received intrapleural fibrinolytics had their IPCs removed, which may have been due to selection bias.

INTRAPLEURAL FIBRINOLYSIS WITH UROKINASE VERSUS ALTEPLASE IN COMPLICATED PLEURAL EFFUSIONS AND EMPYEMA: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL.

Intrapleural fibrinolytic therapy is being used as an effective agent since 1949 in managing complicated pleural effusion and empyema. Several agents like streptokinase (STK), urokinase (UK), and recombinant tissue plasminogen activator (rt-PA) are found to effective with variable effectiveness. However, head-to-head controlled trial to compare the efficacy of the most frequently used i.e., UK and rt-PA (alteplase) in managing complicated pleural effusion has rarely been reported. 50 patients were randomized in two intervention groups i.e., UK and rt-PA. The dose of rt-PA was 10 mg, and that of UK was 1.0 lac unit. UK was given thrice daily for two days, followed by clamping to allow the drugs to retain in the pleural space for 2 hrs. rt-PA was instilled in the pleural space twice daily for two days, and the intercostal drainage was clamped for 1 hour. A total of 50 patients were enrolled for the study out of which84% (n=42) were males and 16 % (n=8) were females. Among them, 30 (60%) patients received UK, and 20 (40%) patients received alteplase as IPFT agents. The of mean changes in the pleural opacity in the UK group was -33.0 % (SD +/- 9.9) and -41.0 % (SD +/- 14.9) in the alteplase group (P-value-0.014). Pain was the most common adverse side effect, occurring in 60% (n=18) of the patients in the UK group and 40% (n=8) in the alteplase group (P-value 0.24) while fever was the second most common side effect. Patient who reported early (within 6 weeks of onset of symptoms) have shown greater response than who reported late for intervention. IPFT is a safe and effective option in managing complicated pleural effusion or empyema, and newer agents like alteplase have greater efficacy and similar adverse effects effect profile when compared with conventional agents like UK.

Severe Pulmonic Valve Endocarditis with Septic Pulmonary Embolism in a Teenager: Case Report

A 14-year-old boy with an uneventful past history suffered from one week of high-grade fever and progressive dyspnea. The patient developed necrotizing pneumonia with massive loculated pleural effusion and septic shock. Echocardiogram revealed a small perimembranous VSD with multiple vegetations at pulmonic valve and both pulmonary arteries. Intravenous antibiotic therapy, mechanical ventilatory support, chest tube placement, and intrapleural fibrinolytic therapy were performed. He was clinically improved after eight weeks of antibiotic therapy. Keywords: Septic pulmonary embolism; Pulmonic valve endocarditis; Infective endocarditis

Benefit of intrapleural fibrinolytic therapy in the treatment of complicated parapneumonic effusion and empyema.

Our study aimed to assess the benefit of intrapleural fibrinolysis before resorting to surgery to treat complicated parapneumonic effusion and empyema. We conducted a retrospective and descriptive study, including all patients hospitalized in the intensive care unit (ICU) of the Abderhaman Mami hospital, Tunisia for empyema treated with instillation of intrapleural fibrinolytic therapy between the 1st January 2000 and 31st December 2016. In all patients, empyema was diagnosed on clinical features, imaging findings (chest X-ray, thoracic echography and/or computed tomography (CT), and microbiological data. The fibrinolytic agent used was streptokinase. The efficiency of intrapleural fibrinolytic therapy was judged on clinical and paraclinical results. Among 103 cases of complicated parapneumonic effusion and empyema, 34 patients were included. The mean age was 34 years [15-81] with a male predominance (sex ratio at 2.77). Median APACH II score was 9. Fifty (50%) of the patients (n=17) had no past medical history; addictive behavior was described in 17 patients (50%). All patients were admitted for acute respiratory failure and one patient for septic shock. Pleural effusion was bilateral in 7 patients. Bacteria isolated were Streptococcus pneumonia (6 cases), Staphylococcus aureus (3 cases, including one which methicillin-resistant), Staphylococcus epidermidis (1 case), anaerobes (5 cases), and Klebsiella pneumoniae (1 case). First-line antimicrobial drug therapy was amoxicillin-clavulanate in 20 patients. A chest drain was placed in all cases in the first 38 hours of ICU admission. The median number of fibrinolysis sessions was 4 [2-9] and the median term of drainage was 7 days [3-16]. No side effects were observed. Video-assisted thoracoscopic surgery was proposed in 5 patients. The median length of hospitalization stay was 15 days [6-31]. One patient died due to multi-organ failure.

A Novel Rabbit Model of Retained Hemothorax with Pleural Organization.

Retained hemothorax (RH) is a commonly encountered and potentially severe complication of intrapleural bleeding that can organize with lung restriction. Early surgical intervention and intrapleural fibrinolytic therapy have been advocated. However, the lack of a reliable, cost-effective model amenable to interventional testing has hampered our understanding of the role of pharmacological interventions in RH management. Here, we report the development of a new RH model in rabbits. RH was induced by sequential administration of up to three doses of recalcified citrated homologous rabbit donor blood plus thrombin via a chest tube. RH at 4, 7, and 10 days post-induction (RH4, RH7, and RH10, respectively) was characterized by clot retention, intrapleural organization, and increased pleural rind, similar to that of clinical RH. Clinical imaging techniques such as ultrasonography and computed tomography (CT) revealed the dynamic formation and resorption of intrapleural clots over time and the resulting lung restriction. RH7 and RH10 were evaluated in young (3 mo) animals of both sexes. The RH7 recapitulated the most clinically relevant RH attributes; therefore, we used this model further to evaluate the effect of age on RH development. Sanguineous pleural fluids (PFs) in the model were generally small and variably detected among different models. The rabbit model PFs exhibited a proinflammatory response reminiscent of human hemothorax PFs. Overall, RH7 results in the consistent formation of durable intrapleural clots, pleural adhesions, pleural thickening, and lung restriction. Protracted chest tube placement over 7 d was achieved, enabling direct intrapleural access for sampling and treatment. The model, particularly RH7, is amenable to testing new intrapleural pharmacologic interventions, including iterations of currently used empirically dosed agents or new candidates designed to safely and more effectively clear RH.

Diagnosis and management of pleural infection.

Pleural infection remains a medical challenge. Although closed tube drainage revolutionised treatment in the 19th century, pleural infection still poses a significant health burden with increasing incidence. Diagnosis presents challenges due to non-specific clinical presenting features. Imaging techniques such as chest radiographs, thoracic ultrasound and computed tomography scans aid diagnosis. Pleural fluid analysis, the gold standard, involves assessing gross appearance, biochemical markers and microbiology. Novel biomarkers such as suPAR (soluble urokinase plasminogen activator receptor) and PAI-1 (plasminogen activator inhibitor-1) show promise in diagnosis and prognosis, and microbiology demonstrates complex microbial diversity and is associated with outcomes. The management of pleural infection involves antibiotic therapy, chest drain insertion, intrapleural fibrinolytic therapy and surgery. Antibiotic therapy relies on empirical broad-spectrum antibiotics based on local policies, infection setting and resistance patterns. Chest drain insertion is the mainstay of management, and use of intrapleural fibrinolytics facilitates effective drainage. Surgical interventions such as video-assisted thoracoscopic surgery and decortication are considered in cases not responding to medical therapy. Risk stratification tools such as the RAPID (renal, age, purulence, infection source and dietary factors) score may help guide tailored management. The roles of other modalities such as local anaesthetic medical thoracoscopy and intrapleural antibiotics are debated. Ongoing research aims to improve outcomes by matching interventions with risk profile and to better understand the development of disease.

Debate 1: Is the Management of Childhood Empyema Primarily Medical, or Surgical?

This review aims to discuss the role of medical and surgical therapy in the management of pediatric empyema. There is considerable debate on the optimal treatment for the same. Early intervention is crucial as it allows rapid recovery of these patients. Antibiotics and adequate pleural drainage form the two pillars in the management of empyema. Chest tube drainage alone has significant failure rates due to its inability to clear loculated effusion. The two main modalities which target these loculations to augment drainage are video-assisted thoracoscopic surgery (VATS) and intrapleural fibrinolytic therapy. The latest evidence shows that both these interventions are equally effective. Children who present late are usually not candidates for intrapleural fibrinolytic therapy or VATS; for them, decortication remains the only option.

Reexpansion Pulmonary Edema After Intrapleural Fibrinolytic Therapy

We report an empyema treated with antimicrobial therapy that developed reexpansion pulmonary edema after intrapleural fibrinolytic and enzyme therapy. Rapid evacuation of pleural fluid likely contributed to the development of reexpansion pulmonary edema.

Effect of Intrapleural Fibrinolytic Therapy vs Surgery for Complicated Pleural Infections

There is a paucity of high-quality prospective randomized clinical trials comparing intrapleural fibrinolytic therapy (IPFT) with surgical decortication in patients with complicated pleural infections. To assess the feasibility, safety, and efficacy of an algorithm comparing tissue plasminogen activator plus deoxyribonuclease therapy with surgical decortication in patients with complicated pleural infections. This parallel pilot randomized clinical trial was performed at a single urban community-based center from March 1, 2019, to December 31, 2021, with follow-up for 90 days. Seventy-four individuals were screened and 48 were excluded. Twenty-six patients 18 years or older with clinical pleural infection and positive findings of pleural fluid analysis were included. Of these, 20 patients underwent randomized selection (10 in each group), and 6 were observed. Intrapleural tissue plasminogen activator plus deoxyribonuclease therapy vs surgical decortication. Primary outcomes were the percentage of patients enrolled to study completion and multidisciplinary adherence. Secondary outcomes included the number of patients with and the reason for inadequate screening, screening to enrollment failures, time to accrual of 20 patients or the number accrued at 1 year, and clinical data. Twenty-six patients were enrolled, 10 were randomized to each group, and 6 were observed. There was 100% enrollment to study completion in each treatment group, no protocol deviations, 2 minor protocol amendments, and no screening to enrollment failures. It took 32 months to enroll 26 patients. The 20 randomized patients had a median age of 57 (IQR, 46-65) years, were predominantly men (15 [75%]), and had a median RAPID (Renal, Age, Purulence, Infection Source, and Dietary Factors) score of 2 (IQR, 1-3). Treatment failure occurred in 1 patient and 2 crossover treatments occurred, all of which were in the IPFT group. Intraprocedure and postprocedure complications were similar between the groups. There were no reoperations or in-hospital deaths. Median duration of chest tube use was comparable in the IPFT (5 [IQR, 4-8] days) and surgery (4 [IQR, 3-5] days) groups (P = .21). Median hospital stay tended to be longer in the IPFT (11 [IQR, 4-18] days) vs surgery (5 [IQR, 4-6] days) groups, although the difference as not significantly different (P = .08). There were no 30-day readmissions or 30- or 90-day deaths. In this pilot randomized clinical trial, the study algorithm was feasible, safe, and efficacious. This provides evidence to move forward with a multicenter randomized clinical trial. ClinicalTrials.gov Identifier: NCT03873766.

Trapped lung: a review of literature and recent cases

A trapped lung, one that cannot expand due to a restrictive fibrous visceral pleural peel, is caused by malignancy, chest trauma, thoracic surgery, complicated infection, and autoimmune conditions. Suspicion for and evaluation of this condition should be considered early on in a patient with history of the above conditions that presents with a chronic pleural effusion of stable volume. Diagnosis is reached with pleural fluid analysis, manometry that shows negative intrapleural pressure that is further reduced with fluid aspiration, and imaging that shows a chronic effusion and pleural thickening. Treatment is dependent on symptomatology and overall patient condition, and ranges from observation to fluid removal, fibrinolytic therapy, talc pleurodesis, indwelling pleural catheter, and surgical decortication. A review of English literature from the last 10 years including case reports, case series, and observational reviews was conducted. A majority of these patients presented with trapped lung due to malignancy, infection, or autoimmune conditions. Treatment varied depending on the cause of the trapped lung, underlying conditions, and patient preference; a majority of these patients received either pleurodesis, intrapleural fibrinolytic therapy, or surgical decortication.

Changes in Etiology and Clinical Outcomes of Pleural empyema during the COVID-19 Pandemic.

Healthcare-seeking behavior changed during the COVID-19 pandemic and might alter the epidemiology of pleural empyema. In this study, the incidence, etiology and outcomes of patients admitted for pleural empyema in Hong Kong in the pre-COVID-19 (January 2015-December 2019) and post-COVID-19 (January 2020-June 2022) periods were compared. Overall, Streptococcus pneumoniae was the predominant organism in <18-year-old patients, while Streptococcus anginosus, anaerobes and polymicrobial infections were more frequent in adults. In the post-COVID-19 period, a marked decline in the incidence of pleural empyema in children was observed (pre-COVID-19, 18.4 ± 4.8 vs. post-COVID-19, 2.0 ± 2.9 cases per year, p = 0.036), while the incidence in adults remained similar (pre-COVID-19, 189.0 ± 17.2 vs. post-COVID-19, 198.4 ± 5.0 cases per year; p = 0.23). In the post-COVID-19 period, polymicrobial etiology increased (OR 11.37, p < 0.0001), while S. pneumoniae etiology decreased (OR 0.073, p < 0.001). In multivariate analysis, clinical outcomes (length of stay, ICU admission, use of intrapleural fibrinolytic therapy, surgical intervention, death) were not significantly different in pre- and post-COVID-19 periods. In conclusion, an increase in polymicrobial pleural empyema was observed during the pandemic. We postulate that this is related to the delayed presentation of pneumonia to hospitals.

Retrospective review comparing intrapleural fibrinolytic therapy (alteplase) and surgical intervention in complex pleural effusion

BackgroundIntrapleural fibrinolytic therapy (IPFT) is one of the treatment options for complex pleural effusion. In this study, the IPFT agent used was alteplase, a tissue plasminogen activator (t-PA). This study aims to determine the difference in the outcome of patients with complex pleural effusion between IPFT and surgery in terms of radiological improvement, inflammatory parameters, length of stay, and post-intervention complications.MethodsA retrospective review of patients with complex pleural effusion treated at Universiti Kebangsaan Malaysia Medical Center from January 2012 to August 2020 was performed. Patient demographics, chest imaging, drainage chart, inflammatory parameters, length of hospital stay, and post-intervention and outcome were analyzed.ResultsFifty-eight patients were identified (surgical intervention, n = 18; 31% and IPFT, n = 40, 69%). The mean age was 51.7 ± 18.2 years. Indication for surgical intervention was pleural infection (n = 18; 100%), and MPE (n = 0). Indications for IPFT was pleural infection (n = 30; 75%) and MPE (n = 10; 25%). The dosages of t-PA were one to five doses of 2–50 mg. The baseline chest radiograph in the IPFT group was worse than in the surgical intervention group. (119.96 ± 56.05 vs. 78.19 ± 55.6; p = 0.029) At week 1, the radiological success rate for IPFT and surgical intervention were 27% and 20%, respectively, and at weeks 4–8, the success rate was 56% and 80% respectively. IPFT was associated with lesser complications; fever (17.5%), chest pain (10%), and non-life-threatening bleeding (5%).ConclusionIPFT was comparable to surgery in radiological outcome, inflammatory parameters, and length of stay with lesser reported complications.

Medical Thoracoscopy and Intrapleural Fibrinolytic Therapy for the Management of Pleural Empyema: A Cohort Study

Background: Pleural empyema is associated with relevant morbidity and mortality, and it may be classified, according to evolution and ultrasound, into three stages: stage I (free-flowing effusion), stage II (viscous effusion with the tendency to loculate), and stage III (organizing phase). According to guidelines, antibiotic therapy and pleural drainage are recommended, with surgery being performed when patients fail and/or in case of organized empyema. Objectives: The aim of the study was to report the efficacy and safety of medical thoracoscopy in patients with pleural empyema stratified by chest ultrasound. Method: Observational retrospective cohort study analyzing patients with pleural empyema treated with medical thoracoscopy. Procedure success and mortality were evaluated at 30 days and 90 days after the procedure; complications were also reported. Results: 131 patients were included. Intrapleural fibrinolytic therapy was performed thereafter in the majority of cases. Medical thoracoscopy was considered successful without subsequent intervention in 99 patients (76%); 19 patients (15%) underwent a second procedure (drainage, thoracoscopy, video-assisted thoracic surgery, or thoracotomy); and 6 patients (5%) died of the evolution of empyema. Patients treated in stages I and II showed significantly better post-procedure results compared with patients treated in stage III (100%, 83.3%, and 58.1%, respectively). Thoracoscopy complications were observed in 18 patients and were reversible in all cases. Conclusions: Patients with pleural empyema treated in earlier stages (free-flowing or multiloculated effusion) with medical thoracoscopy show significantly better results than patients treated in later stages (organized empyema). This approach is safe, minimally invasive, and efficient in these patients with disease having relevant mortality; however, patient selection remains essential.

A Five-Year Study of Intrapleural Fibrinolytic Therapy in Loculated Pleural Collections

Pleural fluid loculations due to complicated parapneumonic effusion (CPE), empyema, tubercular effusion and traumatic hemothorax can be managed either by video-assisted thoracoscopic surgery (VATS) or intrapleural ibrinolytic therapy (IPFT). The former is more invasive, not easily available and is also more expensive. On the other hand, IPFT is less invasive, cheaper, easily accessible and if used early, in loculated pleural collections, break loculations and early pleural peel, thereby facilitating pleural space drainage. To study the efficacy of IPFT in facilitating pleural space drainage in loculated pleural collections of diverse aetiologies. A five-year retrospective, observational study of 200 patients, with loculated pleural collections and failed tube drainage and managed with IPFT was carried out. Responders were defined as those with significant volume of fluid drained and significant radiological resolution. There were 106 (53%) cases of CPE, 59 (29.5%) cases of tubercular effusion, 23 (11.5%) cases of empyema and 12 (6%) cases of hemothorax. Responders were 148 (74%) in number. The distribution of responders as per type of loculated pleural collection was as follows: CPE 88 (83%), tubercular 37 (62.7%), empyema 14 (60.8%) and traumatic hemothorax 11 (91.6%). The adverse effects were mild and included chest pain in six patients and low-grade transient fewer in three cases. Intrapleural fibrinolytic therapy is a safe and cost-effective option in the management of selected patients with loculated pleural effusions.

Management of complicated parapneumonic effusions.

Approximately 36-57% of cases of pneumonia are associated with a parapneumonic effusion (PPE). It begins as sterile effusion, which can quickly evolve to a fibrinopurulent stage with evidence of infection called complicated parapneumonic effusions (CPPE). Marked fibrinous organization then follows. This study focuses on literature synthesis on management of CPPE. Ultrasound has become an indispensable tool in the identification and treatment of CPPE. Prompt antibiotic administration remains the universal standard of care. Decision to drain the fluid is based on fluid staging, characterization and assessment of risk of poor outcomes vs. risk of complications. There is growing evidence to support use of intrapleural fibrinolytic therapy (IPFT) in case of loculated effusions. Newer areas of research include antibodies against plasminogen activator inhibitors and stratification scores that can identify patients at an increased risk. Lastly, timing of surgical referral is an important area under study. Evolution of medical therapy over recent years has increased treatment success rates. Use of IPFT in conjunction to thoracostomy is now the standard of care for loculated effusions. Understanding available therapeutic options, both medical and interventional, can ensure evidence-based practice and improve patient-centred outcomes.

Evaluation of intrapleural fibrinolytic therapy and dosing strategies used for complicated pleural effusions

ObjectivesCompare the use of Tissue Plasminogen Activator (t-PA) and t-PA + Dornase (DNase) for the management of complicated pleural effusions, and to determine if a dose-response relationship exists for t-PA. MethodsRetrospective cohort study that examined all adult patients at a large academic medical center who received intrapleural t-PA or t-PA + DNase for the management of a complicated pleural effusions. Outcomes were success of therapy [defined as avoidance of secondary interventions (i.e. VATSD or thoracotomy)], chest tube output pre- and post-administration, radiographic findings, t-PA dose and frequency, and bleeding complications. ResultsThirty-five patients were enrolled: 25 received t-PA and 10 received t-PA + DNase. Successful pharmacologic treatment occurred in 88% of patients receiving t-PA and 100% of patients receiving t-PA + DNase (p = 0.54). In the t-PA group, chest tube output increased from 75 ml/12 h to 538 ml/12 h after administration of t-PA (p = 0.001), and from 103 ml/12 h to 502 ml/12 h (p = 0.001) in the t-PA + DNase group. Radiographic improvement occurred in 84% of t-PA patients and 90% of t-PA + DNase patients (p = 0.99). In the t-PA group, a successful response occurred in 92% of patients receiving a cumulative dose of ≤10 mg (n = 13) and 83% of patients receiving a cumulative dose of >10 mg (n = 12), p = 0.43. Patients who received a single t-PA dose compared to those who received multiple doses also had similar success rates (p = 1). There was one instance of bleeding following drug administration. ConclusionBoth t-PA and t-PA + DNase were highly effective for reducing a patient's need for surgical intervention. Higher cumulative doses or more frequency administrations did not appear to provide additional benefit.

A Comparative Study of the Safety and Efficacy of Intrapleural Fibrinolysis With Streptokinase and Urokinase in the Management of Loculated Pleural Effusions.

BackgroundIntrapleural fibrinolytic therapy (IPFT) with streptokinase (STK), urokinase (UK), and alteplase remains a common practice for managing loculated pleural effusions (LPEs). However, very limited data are available on the comparative efficacy of these agents.MethodologyWe compared the efficacy and safety of intrapleural streptokinase (n = 28) and urokinase (n = 38) in 66 patients with loculated effusions. IPFT was initiated if effusion remained undrained despite the placement of intercostal chest drainage or pigtail catheter. The dose of STK and UK were 250,000 IU twice daily and 100,000 IU once daily, respectively. The volume of fluid drained after IPFT, radiologic response, clinical response, and adverse events were compared between the two groups.ResultsThe mean volume of fluid drained post-IPFT was 1,379 mL in the STK arm and 1,110 mL in the UK arm (p = 0.251). Of the 66 patients, 53 (80.3%) had good clinical response, and 28 (43.7%) had >75% resolution of effusion on chest radiographs. The clinical (79% vs. 82%; p = 0.765) and radiologic response rates (39.3% vs. 44.6%; p = 0.568) were similar in both STK and UK arms. Pain was the most common adverse event in both groups. Significantly more patients in the STK arm developed fever (14% vs. 0%, p = 0.030). Treatment-limiting adverse events occurred in five patients.ConclusionsIPFT is a safe and effective method for managing patients with LPEs. Although the clinical and radiologic response rates were similar with STK and UK, the latter may be the preferred choice because of its better safety profile and ease of administration (once-daily dose).

Bleeding Risk With Combination Intrapleural Fibrinolytic and Enzyme Therapy in Pleural Infection: An International, Multicenter, Retrospective Cohort Study

Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined. What is the bleeding complication risk associated with IET use in pleural infection? This was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination IET for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria. Overall, pleural bleeding occurred in 76 of 1,833 patients (4.1%; 95%CI, 3.0%-5.0%). Using a half-dose regimen (tissue plasminogen activator, 5mg) did not change this risk significantly (6/172 [3.5%]; P= .68). Therapeutic anticoagulation alongside IET was associated with increased bleeding rates (19/197 [9.6%]) compared with temporarily withholding anticoagulation before administration of IET (3/118 [2.6%]; P= .017). As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of< 100× 109/L were associated with a significant increase in bleeding risk. However, only RAPID score and use of systemic anticoagulation were independently predictive. Apart from pain, non-bleeding complications were rare. IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation but can be mitigated by withholding anticoagulation before IET. Concomitant administration of IET and therapeutic anticoagulation should be avoided. Parameters related to higher IET-related bleeding have been identified that may lead to altered risk thresholds for treatment.

"Burgundy wine" pleural effusion: An unusual manifestation of acute bacterial empyema.

Although empyema diagnosis by thoracentesis is relatively straightforward, the pleural effusion can sometimes be bloody rather than purulent. We report a case of acute empyema with a dark‐red bloody effusion, wherein multiple anaerobic bacteria were detected. Chest imaging findings improved with pleural drainage, intrapleural fibrinolytic therapy, and intravenous antibiotic treatment.