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Advances in Pleural Disease Management Including Updated Procedural CodingPleural Disease and Updated Procedural Coding FREE TO VIEW

Andrew R. Haas, MD, PhD, FCCP; Daniel H. Sterman, MD, FCCP
Author and Funding Information

From the Pulmonary, Allergy, and Critical Care Division, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA.

CORRESPONDENCE TO: Andrew R. Haas, MD, PhD, FCCP, Section of Interventional Pulmonary and Thoracic Oncology, University of Pennsylvania Medical Center, 823 W Gates Bldg, 3600 Spruce St, Philadelphia, PA 19104; e-mail: arhaas@uphs.upenn.edu


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(2):508-513. doi:10.1378/chest.13-2250
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Published online

Over 1.5 million pleural effusions occur in the United States every year as a consequence of a variety of inflammatory, infectious, and malignant conditions. Although rarely fatal in isolation, pleural effusions are often a marker of a serious underlying medical condition and contribute to significant patient morbidity, quality-of-life reduction, and mortality. Pleural effusion management centers on pleural fluid drainage to relieve symptoms and to investigate pleural fluid accumulation etiology. Many recent studies have demonstrated important advances in pleural disease management approaches for a variety of pleural fluid etiologies, including malignant pleural effusion, complicated parapneumonic effusion and empyema, and chest tube size. The last decade has seen greater implementation of real-time imaging assistance for pleural effusion management and increasing use of smaller bore percutaneous chest tubes. This article will briefly review recent pleural effusion management literature and update the latest changes in common procedural terminology billing codes as reflected in the changing landscape of imaging use and percutaneous approaches to pleural disease management.

Figures in this Article

Pleural disease represents a substantial burden to patients and respiratory physicians. Over 1.5 million pleural effusions occur in the United States annually and create troubling dyspnea, chest discomfort, functional limitation, and quality-of-life reduction. In most clinical scenarios, initial pleural effusion etiology evaluation begins with a diagnostic thoracentesis. Depending on the pleural effusion etiology, subsequent chest tube drainage may be required for appropriate management. The development and expanding physical and economic access to handheld portable ultrasound devices has improved noninvasive initial pleural disease evaluation and safety of pleural procedures. This article will briefly review developments in pleural disease management including an update on common procedural terminology (CPT) coding as a result of a shift toward minimally invasive percutaneous pleural procedures and increasing access to ultrasound utilization for pleural procedures.

Ultrasound utilization in pleural disease management allows an operator to assess the pleural lining, the pleural fluid characteristics (anechoic, isoechoic, or hyperechoic), and the complexity of the pleural space. This initial noninvasive information may guide the clinician’s differential diagnosis and his/her diagnostic and/or therapeutic decisions. More importantly, ultrasound permits the clinician to locate a safe access site for pleural intervention, thereby reducing the pneumothorax rate, and can also facilitate rapid postprocedural evaluation for pneumothorax. A recent large observational cohort review of a large hospital claims database demonstrated that ultrasound guidance reduced the rate of pneumothorax by 19%, which reduced overall cost and hospital length of stay.1 Moreover, ultrasound guidance for optimal small-bore pigtail chest tube placement has also been shown to effectively manage multiple pleural effusion etiologies.2 Due to a large body of literature to support ultrasound as a vital tool to garner information regarding pleural disease management, the new CPT codes bundle ultrasound into the procedural code rather than have a separate reportable event (see Assignment of New CPT Codes for Pleural Procedures section).

Talc remains the primary pleurodesing agent in clinical practice today with doxycycline and bleomycin used in some scenarios, although many clinical trials have investigated novel pleurodesing agents such as silver nitrate, iodine solutions, blood, and bacterial superantigens. A review of this topic is beyond the scope of this article, but most pleural experts recognize that pleurodesing agents should not only accomplish successful control of pleural effusion reaccumulation, but also possibly serve as a platform for novel therapeutic approaches.3

Malignant pleural effusions (MPEs) herald advanced-stage malignancy, impact patient quality of life, and portend a poor prognosis with median survival of 6 months. Initial management is often simple ultrasound-guided thoracentesis to ascertain malignant status and simultaneously to relieve associated symptoms and to assess symptom improvement. Upon confirmation of malignant pleural disease, one therapeutic option is to drain the effusion completely and to initiate systemic therapy if the patient is treatment naive, or to alter systemic therapy if the patient has progressed on current treatment. Unfortunately, these approaches often do not control malignant effusion recurrence and a definitive procedure is required.

Several approaches are available to manage MPEs: (1) thoracoscopy/pleuroscopy with pleurodesis; (2) tube thoracostomy with pleurodesis; and (3) indwelling, tunneled pleural catheters (TPCs) (Fig 1). Historically, either tube thoracostomy or thoracoscopy with pleurodesis was the standard approach, and a large randomized trial failed to demonstrate a significant difference in pleurodesis success rate between these two approaches.4 With TPC development, there has been increasing use of this approach to MPE, and several trials have investigated TPC compared with traditional approaches. In a retrospective review, Hunt et al5 reported that patients who had TPCs placed had shorter overall and postprocedure hospital stays and fewer ipsilateral reinterventions for fluid recurrence. Two small randomized prospective trials corroborated these findings, reporting that TPC compared with chest tube with talc pleurodesis resulted in shorter hospital stays, fewer repeat procedures, and improved 30-day survival with effusion control.6,7 The largest trial randomized patients with MPE to either TPC or small-bore chest tube with talc slurry pleurodesis. At 6 weeks, there was no difference in dyspnea scores, but at 6 months, TPC had statistically improved dyspnea compared with talc slurry. Similar to the prior reports, the TPC group had shorter hospital stay (0 days vs 4 days) and less need for further interventions (6% vs 22%), but did have a higher adverse event rate (40% vs 13%) when compared with the talc slurry group.8 Interestingly, in a cost-effectiveness decision analysis comparing thoracentesis, TPC, chest tube with pleurodesis, and thoracoscopic pleurodesis at 3-month and 12-month survival time points, TPC was more cost-effective with shorter life expectancy, while chest tube pleurodesis was better for longer life expectancy.9 The current data are not overwhelmingly convincing that one route is superior to another, so the “best” choice for any given patient with MPE must incorporate several factors–anticipated life expectancy, performance status, lung reexpansion, and patient preference after an informed discussion about the risks/benefits of each approach.

Figure Jump LinkFigure 1  A, A 48-y-old woman with metastatic breast cancer developed a symptomatic, recurrent cytologically positive moderate left pleural effusion. B, After discussing options for management, she chose tunneled pleural catheter (TPC) placement, which resulted in effective palliation of her symptoms and complete evacuation of her pleural fluid. Of note, 9 mo prior she had a right malignant pleural effusion with a TPC in place that resulted in spontaneous pleurodesis.Grahic Jump Location

The inflammatory and/or infectious processes associated with pneumonia can result in pleural fluid development which can be simple exudative fluid, complex multiloculated fluid, or frankly infected purulent fluid. As the continuum along this spectrum occurs, patient morbidity and mortality increases and effective therapeutic interventions become more problematic. The pleural space is often populated with large numbers of active and degenerated neutrophils, lymphocytes and infective organisms, significant fibrinous debris, and nucleic acid components from degenerated cells and infective organisms. Therefore, the pleural space tends to be loculated and filled with viscous material and fluid. Effective therapy to address this potential pneumonia complication is critical to ensure optimal patient outcomes.

Historically, antibiotics with pleural space drainage followed by surgical pleural space debridement and visceral pleura decortication when drainage alone was unsuccessful was the traditional approach to pleural space infection. With the recognition that fibrinous debris was a major component of the intrapleural process and with the advent of fibrinolytic agents, small randomized clinical trials reported a potential role for various fibrinolytics to improve drainage and reduce surgical interventions in pleural space infection.1012 However, the large Multicenter Intrapleural Sepsis Trial (MIST)-1 failed to demonstrate an improvement in mortality, need for surgery, or length of hospital stay when streptokinase was compared with saline.13 Despite these results and given the scientific and clinical support for disruption of the fibrinous and viscous intrapleural material, the MIST2 trial was undertaken using a four-arm double-blind, double-dummy design of tissue plasminogen activator (tPA) plus placebo, deoxyribonuclease (DNase) plus placebo, combined tPA and DNase, or double placebo. Unlike the MIST1 outcome, the MIST2 demonstrated improvement in pleural opacity in the tPA-DNase group compared with either agent alone or placebo.14 Furthermore, combined therapy also demonstrated a reduction in surgical referral and length of hospital stay. These data showed for the first time, to our knowledge, convincing evidence that intrapleural medical therapy when initiated early can be used to effectively manage pleural space infection (Fig 2).

Figure Jump LinkFigure 2  A 56-y-old healthy man had extensive dental work performed and 2 mo later presented with cough, fever, and malaise. A, An initial chest radiograph demonstrated a multiloculated right pleural effusion with probable right lower lobe pneumonia. B, Under ultrasound guidance, a small-bore pigtail catheter was placed into the largest fluid collection through which six doses of tissue plasminogen activator and deoxyribonuclease were administered. The patient had near complete symptomatic and radiographic resolution of his complex effusion following fibrinolysis.Grahic Jump Location

With the advent of minimally invasive thoracic surgical approaches, the question arises as to whether early surgical intervention can have equivalent clinical outcomes with shorter hospital stay, costs, and pain. No randomized trial has compared video-assisted thoracoscopic surgery to tPA-based fibrinolytic therapy in the adult population, but a pediatric trial demonstrated no difference in length of hospital stay, oxygen utilization, days of symptoms, or analgesic use, but did show significantly higher costs for video-assisted thoracoscopic surgery.15 Consequently, a rationale approach in a stable patient may begin with chest tube drainage including fibrinolytic therapy and reserve surgical intervention for clinical or radiographic fibrinolytic failure.

Chest tube drainage was first advocated by Hippocrates when he described the treatment of empyema by means of incision and insertion of intrapleural metal tubes. From this first description of tube thoracostomy until contemporary times, considerable controversy exists about what size chest tube is appropriate in which clinical settings. Typically, chest tubes are divided into small-bore (≤ 14F) vs large-bore (≥ 14F) tubes with smaller tubes generally placed by percutaneous Seldinger approaches and larger-bore tubes by open incision. The theoretical advantage to larger-bore chest tubes in such processes as pleural infection and hemothorax is that a larger-bore tube will allow for drainage of thicker more viscous fluid and be less likely to obstruct.

As a component of the MIST1 trial previously discussed, prospective evaluation of the outcomes relative to quartiles of chest tube size (< 10, 10-14, 15-20, or > 20F) was performed, and demonstrated no difference in mortality or need for surgery based on chest tube size.16 However, there were substantially higher pain scores in patients with large-bore compared with small-bore tubes thereby suggesting that the theoretical advantage to large-bore tubes in pleural infection is nonexistent. Notably, the MIST1 used routine chest tube flushes which is not a routine part of chest tube care in most US hospitals and may explain why small-bore tubes are equally effective with less pain if patency is maintained. For patients undergoing pleurodesis for malignant pleural effusion, similar concerns about small-bore tube obstruction have not borne out in small trials that have demonstrated equal pleurodesis efficacy without greater complications between large- and small-bore chest tubes.1719 Based on the available data, the British Thoracic Society guidelines state that small-bore chest tubes (10-14F) are adequate for most complicated parapneumonic pleural infections and malignant pleural effusions for drainage and pleurodesis without consensus on an optimal size.20

With the proliferation of the Seldinger technique, smaller-bore chest tubes, and increased imaging use for pleural drainage, re-evaluation of the relative value unit (RVU) assignment to pleural drainage was undertaken based on this evolving landscape.21 The original CPT codes for thoracentesis which separated simple fluid aspiration (32421) and temporary catheter placement (32422) for pleural fluid drainage have been eliminated. Use of imaging modalities such as ultrasound, CT scan, or fluoroscopy (CPT 76942) to assist in drainage were separate billable events under the former codes, but have been bundled into the new CPT codes. The new CPT codes differentiate based on use of imaging modality, not method of aspiration (Table 1). CPT code 32554 (thoracentesis, needle or catheter, aspiration of the pleural space, without imaging guidance) is used when any form of temporary pleural drainage is performed without the use of an imaging modality. CPT code 32555 is used for any temporary drainage with imaging modality guidance (ultrasound, CT scan, fluoroscopy).

Table Graphic Jump Location
TABLE 1  ] Current Pleural Procedure CPT Codes

CPT = common procedural terminology.

a 

New CPT codes for 2013.

b 

To be used with CPT 32550 and 32551, not 32555 or 32557.

The increased use of small-bore, percutaneous Seldinger technique chest tubes represented a shift from traditional open tube thoracostomy via cutaneous incision and manual pleural space palpation. Consequently, separate CPT codes have been approved to recognize the difference in effort, risk, and cost of the newer techniques. As imaging is used to optimize chest tube placement, the new percutaneous technique codes are separated based on imaging assistance utilization. CPT code 32556 (pleural drainage, percutaneous, with insertion of indwelling catheter, without imaging guidance) represents percutaneous chest tube placement without imaging guidance, whereas CPT code 32557 represents percutaneous chest tube placement with imaging guidance. If placement of a larger-bore chest tube requiring cutaneous incision, subcutaneous dissection with entry, and palpation into the pleural space is the approach chosen for pleural drainage, the original CPT code 32551 is used. If imaging guidance is used for open tube thoracostomy placement (CPT 32551), CPT code 75989 remains as an add-on code for this effort. CPT code 32550 for placement of a TPC remains intact under the new coding system. Similar to open tube thoracostomy, CPT code 75989 applies for imaging guidance for TPC placement. Subsequent TPC drainages in any setting by a physician or physician extender are not billable events as they are considered routine TPC care. Use CPT code 32552 for TPC removal. In a teaching environment for any billable pleural intervention, the supervising attending must be present for the key and critical component of the procedure and document his/her presence accordingly.

While the aforementioned codes represent the latest update to pleural CPT codes for 2013, since the last update in this journal regarding pleural procedure reimbursement, other CPT codes have been generated for chest tube pleurodesis and for pleural space fibrinolysis. Utilization of any pleurodesing agent through a chest tube represents CPT code 32560 (instillation, via chest tube or catheter, agent for pleurodesis). Should a second pleurodesis be performed, there is a 0-day global period and CPT code 32560 would be repeated. With well-designed studies demonstrating increasing evidence that fibrinolysis may be an effective therapy for complex pleural spaces, CPT codes reflecting its use were generated. Because fibrinolysis is often a multiple instillation event, the CPT codes are divided into an initial instillation at a higher RVU due to the difference in decision-making to begin the therapy and a lower RVU to complete the planned instillation number. CPT code 32561 (instillation, via chest tube/catheter, agent for fibrinolysis, initial day) applies to the initial day of fibrinolytic instillation. CPT code 32562 applies to subsequent day(s) of fibrinolytic agent instillation on that inpatient encounter. As with any billable intervention in a teaching environment, the supervising attending must be present for the key and critical component of the procedure and document his/her presence accordingly. For these CPT codes, the attending must be present for each pleurodesing or fibrinolytic agent instillation.

Pleural disease can represent a substantial patient burden and often requires active intervention by respiratory physicians. More well-designed trials addressing important questions in pleural disease management have been published in the past several years providing some guidance in a field where prior relevant data did not exist. The shift toward less invasive, smaller chest tubes and studies demonstrating their equivalency to larger-bore chest tubes has been a welcome addition to the pleural management armamentarium from both the patient and clinician perspective. Reflecting many of these advances are new pleural procedure CPT codes to ensure clinicians and their institution/practice are reimbursed accordingly for their effort.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

CPT

common procedural terminology

DNase

deoxyribonuclease

MIST

Multicenter Intrapleural Sepsis Trial

MPE

malignant pleural effusion

RVU

relative value unit

tPA

tissue plasminogen activator

TPC

tunneled pleural catheter

Mercaldi CJ, Lanes SF. Ultrasound guidance decreases complications and improves the cost of care among patients undergoing thoracentesis and paracentesis. Chest. 2013;143(2):532-538. [CrossRef] [PubMed]
 
Liu YH, Lin YC, Liang SJ, et al. Ultrasound-guided pigtail catheters for drainage of various pleural diseases. Am J Emerg Med. 2010;28(8):915-921. [CrossRef] [PubMed]
 
Astoul P. Pleurodesis for recurrent malignant pleural effusions: the quest for the Holy Grail. Eur J Cardiothorac Surg. 2011;40(2):277-279. [PubMed]
 
Dresler CM, Olak J, Herndon JE II, et al; Cooperative Groups Cancer and Leukemia Group B; Eastern Cooperative Oncology Group; North Central Cooperative Oncology Group; Radiation Therapy Oncology Group. Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion. Chest. 2005;127(3):909-915. [CrossRef] [PubMed]
 
Hunt BM, Farivar AS, Vallières E, et al. Thoracoscopic talc versus tunneled pleural catheters for palliation of malignant pleural effusions. Ann Thorac Surg. 2012;94(4):1053-1057. [CrossRef] [PubMed]
 
Demmy TL, Gu L, Burkhalter JE, et al; Cancer and Leukemia Group B. Optimal management of malignant pleural effusions (results of CALGB 30102). J Natl Compr Canc Netw. 2012;10(8):975-982. [PubMed]
 
Fysh ET, Waterer GW, Kendall PA, et al. Indwelling pleural catheters reduce inpatient days over pleurodesis for malignant pleural effusion. Chest. 2012;142(2):394-400. [CrossRef] [PubMed]
 
Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA. 2012;307(22):2383-2389. [CrossRef] [PubMed]
 
Puri V, Pyrdeck TL, Crabtree TD, et al. Treatment of malignant pleural effusion: a cost-effectiveness analysis. Ann Thorac Surg. 2012;94(2):374-379. [CrossRef] [PubMed]
 
Davies RJ, Traill ZC, Gleeson FV. Randomised controlled trial of intrapleural streptokinase in community acquired pleural infection. Thorax. 1997;52(5):416-421. [CrossRef] [PubMed]
 
Bouros D, Schiza S, Tzanakis N, Chalkiadakis G, Drositis J, Siafakas N. Intrapleural urokinase versus normal saline in the treatment of complicated parapneumonic effusions and empyema. A randomized, double-blind study. Am J Respir Crit Care Med. 1999;159(1):37-42. [CrossRef] [PubMed]
 
Diacon AH, Theron J, Schuurmans MM, Van de Wal BW, Bolliger CT. Intrapleural streptokinase for empyema and complicated parapneumonic effusions. Am J Respir Crit Care Med. 2004;170(1):49-53. [CrossRef] [PubMed]
 
Maskell NA, Davies CW, Nunn AJ, et al; First Multicenter Intrapleural Sepsis Trial (MIST1) Group. UK controlled trial of intrapleural streptokinase for pleural infection. N Engl J Med. 2005;352(9):865-874. [CrossRef] [PubMed]
 
Rahman NM, Maskell NA, West A, et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011;365(6):518-526. [CrossRef] [PubMed]
 
St Peter SD, Tsao K, Spilde TL, et al. Thoracoscopic decortication vs tube thoracostomy with fibrinolysis for empyema in children: a prospective, randomized trial [published correction appears inJ Pediatr Surg. 2009;44(9):1865]. J Pediatr Surg. 2009;44(1):106-111. [CrossRef] [PubMed]
 
Rahman NM, Maskell NA, Davies CW, et al. The relationship between chest tube size and clinical outcome in pleural infection. Chest. 2010;137(3):536-543. [CrossRef] [PubMed]
 
Parulekar W, Di Primio G, Matzinger F, Dennie C, Bociek G. Use of small-bore vs large-bore chest tubes for treatment of malignant pleural effusions. Chest. 2001;120(1):19-25. [CrossRef] [PubMed]
 
Clementsen P, Evald T, Grode G, Hansen M, Krag Jacobsen G, Faurschou P. Treatment of malignant pleural effusion: pleurodesis using a small percutaneous catheter. A prospective randomized study. Respir Med. 1998;92(3):593-596. [CrossRef] [PubMed]
 
Caglayan B, Torun E, Turan D, et al. Efficacy of iodopovidone pleurodesis and comparison of small-bore catheter versus large-bore chest tube. Ann Surg Oncol. 2008;15(9):2594-2599. [CrossRef] [PubMed]
 
Maskell N; British Thoracic Society Pleural Disease Guideline Group. British Thoracic Society Pleural Disease Guidelines–2010 update. Thorax. 2010;65(8):667-669. [CrossRef] [PubMed]
 
American Medical Association. CPT Professional Edition 2013. Chicago, IL: American Medical Association; 2013.
 

Figures

Figure Jump LinkFigure 1  A, A 48-y-old woman with metastatic breast cancer developed a symptomatic, recurrent cytologically positive moderate left pleural effusion. B, After discussing options for management, she chose tunneled pleural catheter (TPC) placement, which resulted in effective palliation of her symptoms and complete evacuation of her pleural fluid. Of note, 9 mo prior she had a right malignant pleural effusion with a TPC in place that resulted in spontaneous pleurodesis.Grahic Jump Location
Figure Jump LinkFigure 2  A 56-y-old healthy man had extensive dental work performed and 2 mo later presented with cough, fever, and malaise. A, An initial chest radiograph demonstrated a multiloculated right pleural effusion with probable right lower lobe pneumonia. B, Under ultrasound guidance, a small-bore pigtail catheter was placed into the largest fluid collection through which six doses of tissue plasminogen activator and deoxyribonuclease were administered. The patient had near complete symptomatic and radiographic resolution of his complex effusion following fibrinolysis.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1  ] Current Pleural Procedure CPT Codes

CPT = common procedural terminology.

a 

New CPT codes for 2013.

b 

To be used with CPT 32550 and 32551, not 32555 or 32557.

References

Mercaldi CJ, Lanes SF. Ultrasound guidance decreases complications and improves the cost of care among patients undergoing thoracentesis and paracentesis. Chest. 2013;143(2):532-538. [CrossRef] [PubMed]
 
Liu YH, Lin YC, Liang SJ, et al. Ultrasound-guided pigtail catheters for drainage of various pleural diseases. Am J Emerg Med. 2010;28(8):915-921. [CrossRef] [PubMed]
 
Astoul P. Pleurodesis for recurrent malignant pleural effusions: the quest for the Holy Grail. Eur J Cardiothorac Surg. 2011;40(2):277-279. [PubMed]
 
Dresler CM, Olak J, Herndon JE II, et al; Cooperative Groups Cancer and Leukemia Group B; Eastern Cooperative Oncology Group; North Central Cooperative Oncology Group; Radiation Therapy Oncology Group. Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion. Chest. 2005;127(3):909-915. [CrossRef] [PubMed]
 
Hunt BM, Farivar AS, Vallières E, et al. Thoracoscopic talc versus tunneled pleural catheters for palliation of malignant pleural effusions. Ann Thorac Surg. 2012;94(4):1053-1057. [CrossRef] [PubMed]
 
Demmy TL, Gu L, Burkhalter JE, et al; Cancer and Leukemia Group B. Optimal management of malignant pleural effusions (results of CALGB 30102). J Natl Compr Canc Netw. 2012;10(8):975-982. [PubMed]
 
Fysh ET, Waterer GW, Kendall PA, et al. Indwelling pleural catheters reduce inpatient days over pleurodesis for malignant pleural effusion. Chest. 2012;142(2):394-400. [CrossRef] [PubMed]
 
Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA. 2012;307(22):2383-2389. [CrossRef] [PubMed]
 
Puri V, Pyrdeck TL, Crabtree TD, et al. Treatment of malignant pleural effusion: a cost-effectiveness analysis. Ann Thorac Surg. 2012;94(2):374-379. [CrossRef] [PubMed]
 
Davies RJ, Traill ZC, Gleeson FV. Randomised controlled trial of intrapleural streptokinase in community acquired pleural infection. Thorax. 1997;52(5):416-421. [CrossRef] [PubMed]
 
Bouros D, Schiza S, Tzanakis N, Chalkiadakis G, Drositis J, Siafakas N. Intrapleural urokinase versus normal saline in the treatment of complicated parapneumonic effusions and empyema. A randomized, double-blind study. Am J Respir Crit Care Med. 1999;159(1):37-42. [CrossRef] [PubMed]
 
Diacon AH, Theron J, Schuurmans MM, Van de Wal BW, Bolliger CT. Intrapleural streptokinase for empyema and complicated parapneumonic effusions. Am J Respir Crit Care Med. 2004;170(1):49-53. [CrossRef] [PubMed]
 
Maskell NA, Davies CW, Nunn AJ, et al; First Multicenter Intrapleural Sepsis Trial (MIST1) Group. UK controlled trial of intrapleural streptokinase for pleural infection. N Engl J Med. 2005;352(9):865-874. [CrossRef] [PubMed]
 
Rahman NM, Maskell NA, West A, et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011;365(6):518-526. [CrossRef] [PubMed]
 
St Peter SD, Tsao K, Spilde TL, et al. Thoracoscopic decortication vs tube thoracostomy with fibrinolysis for empyema in children: a prospective, randomized trial [published correction appears inJ Pediatr Surg. 2009;44(9):1865]. J Pediatr Surg. 2009;44(1):106-111. [CrossRef] [PubMed]
 
Rahman NM, Maskell NA, Davies CW, et al. The relationship between chest tube size and clinical outcome in pleural infection. Chest. 2010;137(3):536-543. [CrossRef] [PubMed]
 
Parulekar W, Di Primio G, Matzinger F, Dennie C, Bociek G. Use of small-bore vs large-bore chest tubes for treatment of malignant pleural effusions. Chest. 2001;120(1):19-25. [CrossRef] [PubMed]
 
Clementsen P, Evald T, Grode G, Hansen M, Krag Jacobsen G, Faurschou P. Treatment of malignant pleural effusion: pleurodesis using a small percutaneous catheter. A prospective randomized study. Respir Med. 1998;92(3):593-596. [CrossRef] [PubMed]
 
Caglayan B, Torun E, Turan D, et al. Efficacy of iodopovidone pleurodesis and comparison of small-bore catheter versus large-bore chest tube. Ann Surg Oncol. 2008;15(9):2594-2599. [CrossRef] [PubMed]
 
Maskell N; British Thoracic Society Pleural Disease Guideline Group. British Thoracic Society Pleural Disease Guidelines–2010 update. Thorax. 2010;65(8):667-669. [CrossRef] [PubMed]
 
American Medical Association. CPT Professional Edition 2013. Chicago, IL: American Medical Association; 2013.
 
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