A Multicenter, Single-Arm, Prospective Trial Assessing the Diagnostic Yield of Electromagnetic Bronchoscopic and Transthoracic Navigation for Peripheral Pulmonary Nodules.

Rationale: Strict adherence to procedural protocols and diagnostic definitions is critical to understand the efficacy of new technologies. Electromagnetic navigational bronchoscopy (ENB) for lung nodule biopsy has been used for decades without a solid understanding of its efficacy, but offers the opportunity for simultaneous tissue acquisition via electromagnetic navigational transthoracic biopsy (EMN-TTNA) and staging via endobronchial ultrasound (EBUS). Objective: To evaluate the diagnostic yield of EBUS, ENB, and EMN-TTNA during a single procedure using a strict a priori definition of diagnostic yield with central pathology adjudication. Methods: A prospective, single-arm trial was conducted at eight centers enrolling participants with pulmonary nodules (<3 cm; without computed tomography [CT]- and/or positron emission tomography-positive mediastinal lymph nodes) who underwent a staged procedure with same-day CT, EBUS, ENB, and EMN-TTNA. The procedure was staged such that, when a diagnosis had been achieved via rapid on-site pathologic evaluation, the procedure was ended and subsequent biopsy modalities were not attempted. A study finding was diagnostic if an independent pathology core laboratory confirmed malignancy or a definitive benign finding. The primary endpoint was the diagnostic yield of the combination of CT, EBUS, ENB, and EMN-TTNA. Measurements and Main Results: A total of 160 participants at 8 centers with a mean nodule size of 18 ± 6 mm were enrolled. The diagnostic yield of the combined procedure was 59% (94 of 160; 95% confidence interval [CI], 51-66%). Nodule regression was found on same-day CT in 2.5% of cases (4 of 160; 95% CI, 0.69-6.3%), and EBUS confirmed malignancy in 7.1% of cases (11 of 156; 95% CI, 3.6-12%). The yield of ENB alone was 49% (74 of 150; 95% CI, 41-58%), that of EMN-TTNA alone was 27% (8 of 30; 95% CI, 12-46%), and that of ENB plus EMN-TTNA was 53% (79 of 150; 95% CI, 44-61%). Complications included a pneumothorax rate of 10% and a 2% bleeding rate. When EMN-TTNA was performed, the pneumothorax rate was 30%. Conclusions: The diagnostic yield for ENB is 49%, which increases to 59% with the addition of same-day CT, EBUS, and EMN-TTNA, lower than in prior reports in the literature. The high complication rate and low diagnostic yield of EMN-TTNA does not support its routine use. Clinical trial registered with www.clinicaltrials.gov (NCT03338049).

Utilization of palliative care resource remains low, consuming potentially avoidable hospital admissions in stage IV non-small cell lung cancer: a community-based retrospective review.

PURPOSE: Early referral of patients with stage IV non-small cell lung cancer (NSCLC) to outpatient palliative care has been shown to increase survival and reduce unnecessary healthcare resource utilization. We aimed to determine outpatient palliative care referral rate and subsequent resource utilization in patients with stage IV NSCLC in a multistate, community-based hospital network and identify rates and reasons for admissions within a local healthcare system of Washington State. METHODS: A retrospective chart review of a multistate hospital network and a local healthcare system. Patients were identified using ICD billing codes. In the multistate network, 2844 patients diagnosed with stage IV NSCLC between January 1, 2013, and March 1, 2018, were reviewed. In the state healthcare system, 283 patients between August 2014 and June 2017 were reviewed. RESULTS: Referral for outpatient palliative care was low: 8% (217/2844) in the multistate network and 11% (32/283) in the local healthcare system. Early outpatient palliative care (6%, 10/156) was associated with a lower proportion of patients admitted into the intensive care unit in the last 30 days of life compared to no outpatient palliative care (15%, 399/2627; p = 0.003). Outpatient palliative care referral was associated with improved overall survival in Kaplan Meier survival analysis. Within the local system, 51% (104/204) of admissions could have been managed in outpatient setting, and of the patients admitted in the last 30 days of life, 59% (87/147) experienced in-hospital deaths. CONCLUSION: We identified underutilization of outpatient palliative care services within stage IV NSCLC patients. Many patients with NSCLC experience hospitalization the last month of life and in-hospital death.

Cumulative radiation dose incurred during the management of complex pleural space infection.

BACKGROUND: Complex pleural space infections are commonly managed with antibiotics, pleural drainage, intrapleural fibrinolytic therapy, and surgery. These strategies often utilize radiographic imaging during management, however little data is available on cumulative radiation exposure received during inpatient management. We aimed to identify the type and quantity of radiographic studies along with the resultant radiation exposure during the management of complex pleural space infections. METHODS: Retrospective review of community network healthcare system from January 2015 to July 2018. Patients were identified through billing databases as receiving intrapleural fibrinolytic therapy and/or surgical intervention. Patient demographics, clinical outcomes, and inpatient radiographic imaging was collected to calculate cumulative effective dose. RESULTS: A total of 566 patients were identified with 7275 total radiographic studies performed and a median cumulative effective dose of 16.9 (IQR 9.9-26.3) mSv. Multivariable linear regression analysis revealed computed tomography use was associated with increased cumulative dose, whereas increased age was associated with lower cumulative dose. Over 74% of patients received more than 10 mSv, with 7.4% receiving more than 40 mSv. CONCLUSIONS: The number of radiographic studies and overall cumulative effective dose in patients hospitalized for complex pleural space infection was high with the median cumulative effective dose > 5 times normal yearly exposure. Ionizing radiation and modern radiology techniques have revolutionized medical care, but are likely not without risk. Additional study is warranted to identify the frequency and imaging type needed during complex pleural space infection management, attempting to keep ionizing radiation exposure as low as reasonably possible.

Particle size, distribution, and behavior of talc preparations: within the United States and beyond.

PURPOSE OF REVIEW: Talc remains a common sclerosant utilized for pleurodesis. However, the use of talc has documented complications and debate has persisted regarding the safety of talc as well as the differences in talc preparations available throughout the world. We sought to describe an up-to-date review of talc preparations available and the impact these preparations may have on the safety profile of talc. RECENT FINDINGS: Within laboratory-based examinations, talc particle size available within the United States appears to be more consistent with prior reported 'safe' particle sizes. The presence of talc within protein-based solutions appears to modify the overall milieu of the solution and likely results in particle aggregation. SUMMARY: The use of talc remains well accepted for pleurodesis as evidenced by inclusion by multiple guidelines. The medical fields' current understanding of talc and its basic interactions within the pleural space remain limited. Multiple questions related to the pleural space and pleurodesis remain unanswered.

A Prospective, Ex Vivo Trial of Endobronchial Blockade Management Utilizing 3 Commonly Available Bronchial Blockers.

BACKGROUND: Lung isolation with bronchial blockers is a well-described and accepted procedure, often described for use during the management of massive hemoptysis. Recommendations for balloon inflation are sparse, with some advocating for saline whereas other suggest air, including the manufacturers. We sought to evaluate the optimal method for balloon inflation in an ex vivo trial. METHODS: We performed a prospective trial utilizing 3 commercially available bronchial blockers commonly described for use in lung isolation and massive hemoptysis management. We utilized the Arndt Endobronchial Blocker (Cook Medical), the Cohen Tip Deflecting Endobronchial Blocker (Cook Medical), and the Fogarty Venous Thrombectomy Catheter (Edwards LifeSciences). Balloon size and deflation assessment were tested within 3 different scenarios comparing air versus saline.Welch t test was performed to compare means between groups, and a generalized estimating equation model was utilized to compare balloon diameter over time to account for correlation among repeated measures from the same balloon. RESULTS: All 3 endobronchial blocker systems were observed in triplicate. During free-standing balloon inflation, all 3 endobronchial systems displayed a greater degree of balloon deflation over time with air as opposed to saline (P < .001). Within a stent-based model, inflation with air of all 3 endobronchial systems, according to manufacturer recommendations, demonstrated significantly decreased time until fluid transgression occurred when compared to a saline model (P < .001). Within a stent-based model, inflation with air, according to clinical judgment, demonstrated significantly decreased time until fluid transgression in the Arndt (P = .016) and the Fogarty (P < .001) system, but not the Cohen (P = .173) system, when compared with saline. CONCLUSIONS: The utilization of saline for balloon inflation during bronchial blockade allows for more consistent balloon inflation. The use of saline during balloon inflation appears to delay passive, spontaneous balloon deflation time when compared to air during a model of endobronchial blockade. The approach of saline inflation should be tested in humans to demonstrate the overall applicability and validity of the current findings.

Tunneled pleural catheter use for pleural palliation does not increase infection rate in patients with treatment-related immunosuppression.

PURPOSE: Concerns for infections resulting from antineoplastic therapy-associated immunosuppression may deter referral for symptom palliation with a tunneled pleural catheter (TPC) in patients with malignant/para-malignant pleural effusions (MPE/PMPE). While rates of TPC-related infections range from 1 to 21%, those in patients receiving antineoplastic therapy with correlation to immune status has not been established. We aimed to assess TPC-related infection rates in patients on antineoplastic therapy, determine relation to immune system competency, and assess impact on the patient. METHODS: Patients with a MPE/PMPE undergoing TPC management associated with antineoplastic therapy, from 2008 to 2016, were reviewed and categorized into those with an immunocompromised versus immunocompetent immune status. RESULTS: Of the 150 patients, a TPC-related infection developed in 13 (9%): pleural space in 11 (7%) and superficial in 2 (1%). Ninety-three percent (139/150) were identified to be immunocompromised during their antineoplastic therapy. No difference in TPC-related infections was seen in patients with an immunocompromised (9%, 12/139) versus immunocompetent status (9%, 1/11); p = 0.614. The presence of a catheter-related infection did not negatively impact overall survival over a median follow-up of 144 days (interquartile range 41-341); p = 0.740. CONCLUSIONS: These results suggest that antineoplastic therapy may not significantly increase the overall risk of TPC-related infections, as the rate remains low and comparable to rates in patients not undergoing antineoplastic therapy. Regardless of immune status, the presence of a catheter-related infection did not negatively impact overall survival. These results should reassure clinicians that the need to initiate antineoplastic therapy should not delay definitive pleural palliation with a TPC.

Use of intrapleural tissue plasminogen activator and deoxyribonuclease in pleural space infections: an update on alternative regimens.

PURPOSE OF REVIEW: Pleural infection remains a common problem with significant associated morbidity and mortality. The current treatment paradigm for pleural infection appears to be shifting as more recent data have suggested that the use of intrapleural fibrinolytic therapy (IPFT) may be adequate for treatment, potentially avoiding the need for surgical intervention in a significant number of patients. RECENT FINDINGS: The previous Multicenter Intrapleural Sepsis Trial demonstrated improved outcomes when utilizing combined IPFT, however, more recently alterations in this dosing regimen have been explored. Successful retrospective studies have examined the role of extended dosing (more than six sequential doses), concurrent dosing (instilling both medications together as opposed to separate medication dwell times), and daily dosing of intrapleural medications. SUMMARY: Although the use of IPFT is likely shifting the management of pleural infection to less surgical intervention, the optimal dosing strategy of intrapleural therapy remains undefined. Within the last few years more data on variations of IPFT have emerged. This data remains of lower quality because of its retrospective nature and future prospective evaluation is required to further define the optimal dosing regimen for IPFT in complicated pleural space infections.

Diagnostic Yield and Complications of Bronchoscopy for Peripheral Lung Lesions. Results of the AQuIRE Registry.

RATIONALE: Advanced bronchoscopy techniques such as electromagnetic navigation (EMN) have been studied in clinical trials, but there are no randomized studies comparing EMN with standard bronchoscopy. OBJECTIVES: To measure and identify the determinants of diagnostic yield for bronchoscopy in patients with peripheral lung lesions. Secondary outcomes included diagnostic yield of different sampling techniques, complications, and practice pattern variations. METHODS: We used the AQuIRE (ACCP Quality Improvement Registry, Evaluation, and Education) registry to conduct a multicenter study of consecutive patients who underwent transbronchial biopsy (TBBx) for evaluation of peripheral lesions. MEASUREMENTS AND MAIN RESULTS: Fifteen centers with 22 physicians enrolled 581 patients. Of the 581 patients, 312 (53.7%) had a diagnostic bronchoscopy. Unadjusted for other factors, the diagnostic yield was 63.7% when no radial endobronchial ultrasound (r-EBUS) and no EMN were used, 57.0% with r-EBUS alone, 38.5% with EMN alone, and 47.1% with EMN combined with r-EBUS. In multivariate analysis, peripheral transbronchial needle aspiration (TBNA), larger lesion size, nonupper lobe location, and tobacco use were associated with increased diagnostic yield, whereas EMN was associated with lower diagnostic yield. Peripheral TBNA was used in 16.4% of cases. TBNA was diagnostic, whereas TBBx was nondiagnostic in 9.5% of cases in which both were performed. Complications occurred in 13 (2.2%) patients, and pneumothorax occurred in 10 (1.7%) patients. There were significant differences between centers and physicians in terms of case selection, sampling methods, and anesthesia. Medical center diagnostic yields ranged from 33 to 73% (P = 0.16). CONCLUSIONS: Peripheral TBNA improved diagnostic yield for peripheral lesions but was underused. The diagnostic yields of EMN and r-EBUS were lower than expected, even after adjustment.

Interventional pulmonology in the pediatric population.

Endoscopic airway interventions within pediatric populations vary considerably. Some of this variance may be related to institutional experience, however, may also be limited by operator experience and available equipment. Previous reports of pediatric bronchoscopic interventional procedures have been identified within the surgical literature; however, newer reports have identified other specialties participating in the care of these patients. Here, we will provide a review of the current relevant medical literature, including an evidence-based review of advanced diagnostic and therapeutic bronchoscopic treatments within the pediatric population.

The effect of pleural drainage on pulse oximetry in a post-operative thoracic surgery population.

BACKGROUND: Pleural effusions in post-operative thoracic surgery patients are common. Effusions can result in prolonged hospitalizations or readmissions, with prior studies suggesting mixed effects of pleural drainage on hypoxia. We aimed to define the impact of pleural drainage on pulse oximetry (SpO2) in post-thoracic surgery patients. METHODS: A retrospective study of post-operative thoracic surgery patients undergoing pleural drainage was performed. SpO2 and supplemental oxygen (FiO2) values were recorded at pre- and post-procedure. The primary outcome was difference in pre-procedural and post-procedural SpO2. RESULTS: We identified 95 patients with a mean age of 65 (SD - 13.8) years undergoing 122 pleural drainage procedures. Mean drainage volume was 619 (SD-423) mL and the majority of procedures (88.5 %) included a drainage of <1000 mL. SpO2 was associated with an increase from 94.0 % (SD-2.6) to 97.3 % (SD-2.0) at 24-h (p < 0.0001). FiO2 was associated with a decrease from 0.31 (SD-0.15) to 0.29 (SD-0.12) at 24-h (p = 0.0081). SpO2/FiO2 was associated with an increase from 344.5 (SD-99.0) to 371.9 (SD-94.7) at 24-h post-procedure (p < 0.0001). CONCLUSIONS: Pleural drainage within post-operative thoracic surgery patients offers statistically significant improvements in oxygen saturation by peripheral pulse oximetry and oxygen supplementation; however the clinical significance of these changes remains unclear. Pleural drainage itself may be requested for numerous reasons, including diagnostic (fevers, leukocytosis, etc.) or therapeutic (worsening dyspnea) evaluation. However, pleural drainage may offer minimal clinical impact on pulse oximetry in post-operative thoracic surgery patients.

Access to Lung Cancer Screening Among American Indian and Alaska Native Adults: A Qualitative Study.

BACKGROUND: Lung cancer is the leading cause of cancer mortality among American Indian and Alaska Native populations. American Indian and Alaska Native people use commercial tobacco products at higher rates compared with all other races and ethnicities. Moreover, they show lower adherence to cancer screening guidelines. RESEARCH QUESTION: How do American Indian and Alaska Native adults perceive and use lung cancer screening? STUDY DESIGN AND METHODS: We conducted a study in which we recorded and transcribed data from three focus groups consisting of American Indian and Alaska Native adults. Participants were recruited through convenience sampling at a national health conference. Transcripts were analyzed by inductive coding. RESULTS: Participants (n = 58) of 28 tribes included tribal Elders, tribal leaders, and non-Native volunteers who worked with tribal communities. Limited community awareness of lung cancer screening, barriers to lung cancer screening at health care facilities, and health information-seeking behaviors emerged as key themes in discussions. Screening knowledge was limited except among people with direct experiences of lung cancer. Cancer risk factors such as multigenerational smoking were considered important priorities to address in communities. Limited educational and diagnostic resources are significant barriers to lung cancer screening uptake in addition to limited discussions with health care providers about cancer risk. INTERPRETATION: Limited access to and awareness of lung cancer screening must be addressed. American Indian and Alaska Native adults use several health information sources unique to tribal communities, and these should be leveraged in designing screening programs. Equitable partnerships between clinicians and tribes are essential in improving knowledge and use of lung cancer screening.

Safety and Outcomes of Outpatient Pleural Drainage in Symptomatic Postoperative Cardiac Surgery Patients.

BACKGROUND: Symptomatic pleural effusions and anticoagulant/antiplatelet medication use in postoperative cardiac surgery are common. Guidelines and recommendations are currently mixed regarding medication management related to invasive procedure performance. We aimed to describe the outcomes of postoperative cardiac surgery patients referred for outpatient, symptomatic pleural effusion management. METHODS: A retrospective study of post-cardiac surgery patients undergoing outpatient thoracentesis from 2016 to 2021 was performed. Demographics, operative details, pleural disease characteristics, outcomes, and complications were collected. Odds ratios with confidence intervals were estimated and adjusted by multivariate logistic regression to investigate the association with multiple thoracenteses. RESULTS: A total of 110 patients underwent 332 thoracenteses. The median age was 68 years and most common operation was coronary artery bypass. Anticoagulation or antiplatelet use was identified in 97%. Thirteen complications were identified, with all major complications (n=3) related to bleeding. The amount of fluid present at the time of initial thoracentesis (>1500 milliliters) was associated with increased odds ratio of subsequent multiple thoracentesis (Unadjusted odds ratio, 6.75 (CI - 1.43 to 31.9). No other variables had a significant association with the need for multiple procedures. CONCLUSION: Within a postoperative cardiac surgery population presenting with symptomatic pleural disease, we observed that thoracentesis performed on antiplatelet and/or anticoagulant medication is relatively safe. We also identified that many patients can be managed as outpatients and that most pleural effusions remain self-limited. The presence of larger amounts of pleural fluid at initial thoracentesis may be associated with increased odds for additional drainage.

Muscle mass cross-sectional area is associated with survival outcomes in malignant pleural disease related to lung cancer.

INTRODUCTION: Malignant pleural effusions are common in advanced malignancy and associated with overall poor survival. The presence of sarcopenia (decreased muscle mass) is associated with poor outcomes in numerous disease states, however, its relationship to malignant pleural disease has not been defined. We sought to understand if there was an association between decreased survival and decreased muscle mass in patients with malignant pleural effusion. METHODS: Patients with malignant pleural disease undergoing indwelling tunneled pleural catheter placement were retrospectively reviewed. Computed tomography was reviewed and cross-sectional area of pectoralis and paraspinous muscle areas were calculated. Overall survival and associations with muscle mass were calculated. RESULTS: A total of 309 patients were available for analysis, with a median age of 67 years and the majority female (58%). The median survival was 129 days from initial pleural drainage to death. Regression analysis and Kaplan-Meier survival analysis did not reveal an association with survival and muscle mass for the entire population. However, Kaplan-Meier survival analysis of the lung cancer subgroup revealed the presence of decreased muscle mass and decreased survival time. CONCLUSION: The presence of decreased muscle mass within a lung cancer population that has malignant pleural effusions are associated with decreased survival. However, the presence of decreased muscle mass within a heterogenous population of malignant pleural disease was not associated with decreased overall survival time. Further study of the role that sarcopenia may play in malignant pleural disease is warranted.

Effect of Intrapleural Fibrinolytic Therapy vs Surgery for Complicated Pleural Infections: A Randomized Clinical Trial.

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Interventions: Intrapleural tissue plasminogen activator plus deoxyribonuclease therapy vs surgical decortication. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT03873766.

Pleural Interventions in the Management of Hepatic Hydrothorax.

Hepatic hydrothorax can be present in 5% to 15% of patients with underlying cirrhosis and portal hypertension, often reflecting advanced liver disease. Its impact can be variable, because patients may have small pleural effusions and minimal pulmonary symptoms or massive pleural effusions and respiratory failure. Management of hepatic hydrothorax can be difficult because these patients often have a number of comorbidities and potential for complications. Minimal high-quality data are available for guidance specifically related to hepatic hydrothorax, potentially resulting in pulmonary or critical care physician struggling for best management options. We therefore provide a Case-based presentation with management options based on currently available data and opinion. We discuss the role of pleural interventions, including thoracentesis, tube thoracostomy, indwelling tunneled pleural catheter, pleurodesis, and surgical interventions. In general, we recommend that management be conducted within a multidisciplinary team including pulmonology, hepatology, and transplant surgery. Patients with refractory hepatic hydrothorax that are not transplant candidates should be managed with palliative intent; we suggest indwelling tunneled pleural catheter placement unless otherwise contraindicated. For patients with unclear or incomplete hepatology treatment plans or those unable to undergo more definitive procedures, we recommend serial thoracentesis. In patients who are transplant candidates, we often consider serial thoracentesis as a standard treatment, while also evaluating the role indwelling tunneled pleural catheter placement may play within the course of disease and transplant evaluation.

Comparing Initial Surgery versus Fibrinolytics for Pleural Space Infections: A Retrospective Multicenter Cohort Study.

Rationale: When drainage of complicated pleural space infections alone fails, there exists two strategies in surgery and dual agent-intrapleural fibrinolytic therapy; however, studies comparing these two management strategies are limited. Objectives: To determine the outcomes of surgery versus fibrinolytic therapy as the primary management for complicated pleural space infections (CPSI). Methods: A retrospective review of adults with a CPSI managed with surgery or fibrinolytics between 1/2015 and 3/2018 within a multicenter, multistate hospital system was performed. Fibrinolytics was defined as any dose of dual-agent fibrinolytic therapy and standard fibrinolytics as 5-6 doses twice daily. Treatment failure was defined as persistent infection with a pleural collection requiring intervention. Crossover was defined by any fibrinolytics after surgery or surgery after fibrinolytics. Logistic regression with inverse probability of treatment weighting (IPTW) were employed to account for selection bias effect of management strategies in treatment failure and crossover. Results: We identified 566 patients. Surgery was the initial strategy in 55% (311/566). The surgery group had less additional treatments (surgery: 10% [32/311] versus fibrinolytics: 39% [100/255], P < 0.001), treatment failures (surgery: 7% [22/311] versus fibrinolytics: 29% [74/255], P < 0.001), and crossovers (surgery: 6% [20/311] versus fibrinolytics: 19% [49/255], P < 0.001). Logistic regression analysis with IPTW demonstrated a lower odds of treatment failure with surgery compared with any fibrinolytics (odds ratio [OR], 0.20; 95% confidence interval [CI], 0.10-0.30; P < 0.001); and compared with standard fibrinolytics (OR, 0.20; 95% CI, 0.11-0.35; P < 0.001). Conclusions: Although there is a lack of consensus as to the optimal management strategy for patients with a CPSI, in surgical candidates, operative management may offer more benefits and could be considered early in the management course. However, our study is retrospective and nonrandomized; thus, prospective trials are needed to explore this further.

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

BACKGROUND: 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. RESEARCH QUESTION: What is the bleeding complication risk associated with IET use in pleural infection? STUDY DESIGN AND METHODS: 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. RESULTS: 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, 5 mg) 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. INTERPRETATION: 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.