Treating Recurrent Pleural Disease: A Review of Indications and Technique for Chemical Pleurodesis for the Interventional Radiologist

Abstract

Pleural space diseases such as recurrent pleural effusion and pneumothorax inflict a significant symptomatic burden on patients. Guidelines and studies are available to guide best practices in the setting of refractory effusions, mostly in the setting of malignancy, and recurrent pneumothorax. Less data is available to guide management of refractory transudative effusions. Recurrent pleural effusions can be treated with tunneled pleural catheters or catheter-based pleurodesis. While refractory transudative effusions can benefit from tunneled pleural catheter, this is an area of ongoing research. Regarding recurrent pneumothorax, video-assisted thoracoscopic surgery (VATS) pleurodesis using mechanical or laser/argon beam coagulation is the most effective means of preventing recurrence. Catheter based pleurodesis, a less invasive means of administering chemical sclerosant via percutaneous thoracostomy tube, is only used when surgery is not an option. However, both approaches induce inflammation of the pleural space, resulting in adherence of the parietal and visceral pleura to prevent fluid or air re-accumulation. This article will discuss catheter based chemical pleurodesis geared toward the interventional radiologist, including a review of disease processes and indications, technique, and strategies to mitigate complications as well as a literature review comparing percutaneous chemical pleurodesis to other therapies.

Pleurodesis induces inflammation and adhesions between the visceral and parietal pleura which obliterates the intrapleural potential space, thus preventing re-accumulation of fluid or air. This can be accomplished mechanically or chemically. Mechanical pleurodesis is accomplished by direct abrasion or laser/argon beam coagulation during open thoracotomy or, more commonly, during video-assisted thoracoscopic surgery (VATS). Chemical pleurodesis is accomplished by intrapleural sclerosis using various inflammatory agents and can be infused through a percutaneous thoracostomy tube or insufflated via VATS. Historically, many different sclerosants have been used, including talc, tetracycline, doxycycline, minocycline, bleomycin, povidone-iodine, and autologous blood (known also as “blood patch”), with the goal of causing pleural symphysis via fibroblast-mediated fibrosis. Of these sclerosants, talc is the most well-studied, cost-effective agent available and is overall the most well-tolerated. ¹ Favored due to its minimally invasive approach, catheter based chemical pleurodesis is indicated for recurrent malignant pleural effusion, which is its most common application. It has an emerging role in second-line treatment of recurrent primary and secondary spontaneous pneumothorax when refractory or unamenable to surgical treatment. It is essential to consider the underlying etiology of pleural space disease, and to consider patient performance status, prognosis, comorbidities, and preferences when considering pleurodesis versus other available treatment options in these patients.

Pleural Effusions: Pathophysiology and Management

Pleural effusions occur due to an imbalance of normal hydrostatic and interstitial pressure gradients which dictate physiologic fluid movement, summarized by the Starling forces equation ( Fig. 1a ). There is normally a small amount of physiologic fluid (0.1 ml/kg) within the intrapleural space, with a turnover rate of approximately 3.6 ml/kg daily. ² Pleural effusions occur due to an imbalance of normal hydrostatic and interstitial pressure gradients which dictate physiologic fluid movement, and can lead to potentially debilitating dyspnea, cough, and pleuritic chest pain. An understanding of the etiology of the pleural fluid is necessary to determine the appropriate treatment.

Fig. 1.

( a ) Pleural effusions are secondary to an imbalance of the Starling forces that dictate physiologic balance between capillary filtration (↓) and absorption (↑). Transudative effusions are often secondary to decreased oncotic pressure or increased hydrostatic pressure. Meanwhile, exudative effusions are secondary to increased permeability of the pleural membrane, inflammatory cytokines release, or lymphatic obstruction. ( b ) The goal of pleurodesis, achieved either via chemical sclerosant, mechanical abrasion or autopleurodesis is fibroblast-mediated inflammation that forms adhesions that enable pleural symphysis and prevent fluid from reaccumulating in the pleural space.

Fluid accumulation occurs due to a variety of mechanisms which fall into two broad categories: transudative or exudative effusions. Lights criteria, which is 99.5% sensitive at identifying an exudative effusion, and 93-96% sensitive in differentiating exudative from transudative effusion, can help differentiate between these two broad categories and help guide management. An exudate is almost certainly present if one or more of the following are true: (1) the ratio of pleural fluid protein to serum protein is greater than 0.5, (2) the ratio of pleural fluid lactate dehydrogenase (LDH) to serum LDH is greater than 0.6, or (3) the pleural fluid LDH level is greater than two thirds of the upper limit of normal for serum LDH. ³

Transudates are secondary to an imbalance in hydrostatic and oncotic forces, most commonly from congestive heart failure and cirrhosis, and less commonly from atelectasis, hypoalbuminemia, renal failure or nephrotic syndrome. ⁴ In general, transudative effusions respond to treatment of the underlying condition, which may include diuresis in heart failure, dialysis in renal failure, or transjugular intrahepatic portosystemic shunt (TIPS) creation for hepatic hydrothorax. However, when effusions are refractory to standard therapies and symptoms persist, palliation becomes challenging ⁵ and requires individualization based on the patient's performance status, prognosis, comorbidities, and preferences. ⁶

The data available to evaluate pleurodesis for nonmalignant transudative effusions is limited by small sample sizes, lack of reporting on morbidity and mortality, and heterogeneity in the definitions of success. ⁷ In patients with heart failure, few small retrospective studies demonstrate pleurodesis to be safe and effective, successfully preventing recurrence in approximately 85-95% of patients. ^{6 7} In those patients with underlying cirrhosis and hepatic hydrothorax, the literature is equally as sparse, with lower and more variable reported success rates (37-72%). ^{5 8} Additionally, overall complication rates are described as high as 80%. ⁸ De Campos et al. reported morbidity and mortality after thoracoscopic pleurodesis at 57% and 39%, respectively. ⁹

Tunneled pleural catheters (TPC) have become more frequently utilized in the setting of nonmalignant transudative effusions. In comparison to pleurodesis, TPC's offer equivalent palliation with fewer hospital days and periprocedural respiratory complications. ⁶ Additionally, autopleurodesis is highly variable, reported as occurring in anywhere from 25–70% of patients after 2-3 months of TPC duration, at which time the catheter was removed and there was usually no need for future procedures. ^{10 11 12} While the mechanism for TPC autopleurodesis is not fully understood, it is suspected to be due to pleural irritation from the catheter itself as well as repeat fluid drainage, which causes pleural symphysis ( Fig. 1b ). ¹³ However, the potentially prolonged length of catheter dwell time may increase the risk of delayed infection, which has been reported as high as 50%, with an empyema rate of 12%. ¹⁴

In contradistinction to transudative effusions, exudative effusions occur when local factors change that affect fluid accumulation. This includes an increase in pleural membrane permeability, a release of inflammatory cytokines which increase fluid production, or an obstruction in lymphatic flow. ^{3 4} Pneumonia, malignancy, and thromboembolism account for most exudative effusions in the United States. ¹⁵ Parapneumonic effusions stemming from pulmonary abscess or pneumonia are the most common. These typically resolve with antibiotics, although if treatment is delayed and an uncomplicated parapneumonic effusion progresses to a complicated parapneumonic effusion or empyema, urgent pleural space drainage with a thoracostomy tube is warranted. Pleurodesis has no role for parapneumonic effusions and is contraindicated in this setting. ¹⁶

Malignant pleural effusions (MPE), which are characterized by the presence of malignant cells, have been a focus of research due to significant morbidity and impact on patient's quality of life. ^{17 18} There are 150,000–175,000 cases annually in the United States resulting in an estimated 125,000 hospital admissions per year. ^{19 20} Median survival ranges from 4-12 months. ^{21 22 23 24} Approximately 80% of MPE are due to lung, breast, ovarian, and gastric cancers as well as lymphoma. ^{20 25} Compared to the data available for recurrent transudative effusions, there is robust research in this population available to guide therapy, including prospective randomized control trials and evidence based clinical guidelines. ^{17 24 26 27} The goal of treatment is aimed at relieving symptoms in a minimally invasive manner and limiting the need for repeated procedures and hospital visits. ¹⁷

Based on the available evidence, the American Thoracic Society (ATS), Society of Thoracic Surgeons (STS), and Society of Thoracic Radiology (STR) updated guidelines in 2018 recommend either chemical pleurodesis or TPC as first line treatment for symptomatic MPE. ¹⁷ The British Thoracic Society guidelines, last updated in 2010, continue to recommend chemical pleurodesis as first line therapy. ²⁸ It is worth noting that TPC offers the added benefit of shorter hospital stay ^{19 26 29} and high rates of patient reported satisfaction. ²³ However, TPCs requires patient, family or home health support for catheter drainage and management. Additionally, there is a higher risk of local catheter infection and catheter dislodgement. If patients lack resources for follow-up and home care, or if there is a higher risk of infection, then pleurodesis may be favored over TPC. ^{30 31 32}

In instances when life expectancy is less than 90 days and accumulation of fluid is slow, repeated large-volume thoracentesis may be considered for palliation. ^{1 28} However, in most cases large volume thoracentesis is not a definitive therapy and generally not recommended for treating MPE. It does play an important initial role in cytologic diagnosis and treatment planning. Complete thoracentesis fluid drainage and lung re-expansion can exclude trapped lung, when thickening of the visceral pleural prevents lung re-expansion; a setting in which pleurodesis would be contraindicated. ^{28 33 34} It also confirms that symptoms are relieved when fluid is removed and are not caused by another etiology such as pulmonary embolism or pericardial effusion. The ATS/STS/STR 2018 guidelines recommend TPC in cases of trapped lung, and instead of repeat pleurodesis when the first attempt has failed. ^{17 34}

Finally, it is worth comparing percutaneous catheter based chemical pleurodesis to VATS-guided pleurodesis. Multiple randomized control trials have compared talc slurry infusion via percutaneous catheter to talc poudrage insufflation during VATS for malignant effusions and have found no significant difference in pleurodesis success rate, hospital stay or respiratory complications. ^{35 36 37 38}

Catheter based chemical pleurodesis offers advantages in efficiency and cost, as it can be performed at bedside without anesthesia or operating room resources. ^{37 39} VATS does offer benefits of direct visual inspection and lysis of adhesions/ decortication. ⁴⁰

Spontaneous Pneumothorax: Pathophysiology and Management

Pneumothorax occurs due to increased transmural pressure in the pleural cavity causing lung collapse. During inhalation, air will enter the lungs as well as the intrathoracic chest cavity through a defect in the pleura until a steady state is reached. ⁴¹ Irrespective of cause, the total incidence of pneumothorax is 22.7 cases per 100,000. ^{42 43} Spontaneous pneumothorax can occur in otherwise healthy individuals and in patients with underlying lung disease. The former is categorized as primary spontaneous pneumothorax (PSP) and has a higher prevalence in tall thin males and those with a family history of pneumothorax. ⁴⁴ The latter is categorized as secondary pneumothorax (SSP) and is most common in adults over age 55, with chronic obstructive pulmonary disease being the most common underlying lung pathology. ^{19 20} Smoking is an additional risk factor for all comers. ⁴⁵ In the absence of underlying lung disease, a pneumothorax usually occurs due to subpleural blebs and bullae which rupture.

Differentiation of primary versus secondary pneumothorax is important. While healthy patients are more likely to be asymptomatic or have mild symptoms and recover with minimal or no intervention, patients with pre-existing lung disease are less tolerant of a pneumothorax, are more likely to be symptomatic even if the pneumothorax is small, and require more complex management. ⁴⁶ There is a lack of prospective randomized controlled trials to guide management in both primary and secondary spontaneous pneumothorax, and therefore international guidelines are based mainly on expert opinion. ⁴⁷

In the first occurrence of PSP, treatments range from observation to aspiration or catheter drainage, with no role for catheter based chemical pleurodesis. ^{46 47} Rates of recurrence vary in the literature but may be as high as 30% for primary spontaneous pneumothorax, with the risk highest in the first year. ⁴⁸ After a second episode, the recurrence rate increases to 60-80%. ^{48 49} Given the high risk of second recurrence, prevention of further episodes is a main goal for clinicians, and first line treatment is VATS. VATS allows for visualization and possible resection of blebs and bulla, repair of pleural porosity via pleurectomy, and inclusion of mechanical and/or chemical pleurodesis. ⁴⁶ Historically, surgical treatment involving open thoracotomy with pleurectomy and bullectomy was the standard treatment, usually performed in conjunction with mechanical pleurodesis. However, studies have demonstrated little to no difference between recurrence rates of VATS (5%) versus thoracotomy (1%), with less morbidity with VATS. ^{50 51 52} In comparison, catheter based chemical pleurodesis success rates are significantly lower, in the range of 78 to 91%. ⁴⁷ Therefore, chemical pleurodesis is only recommended for those patients who wish to avoid surgery or have a high surgical risk. ^{46 47}

Treating SSP involves a more nuanced treatment algorithm due to the presence of underlying lung disease and a higher inherent surgical risk. Unlike in patients with PSP, patients with underlying lung disease usually require hospitalization due to the high risk for respiratory decompensation, even when clinically stable. ⁴⁶ Additionally, these patients are managed more aggressively when symptomatic, with nearly all requiring percutaneous catheter decompression. ⁴⁷ Surgical consultation is generally initiated after the first occurrence of SSP, as the likelihood of spontaneous resolution of the air leak is less likely, and the mortality rate is high with recurrence. ^{46 47 53} In fact, the American College of Chest Physicians 2001 guidelines recommend chest tube decompression followed by surgical bullectomy and some form of pleurodesis in all first episodes of SSP. ⁴⁷ As in PSP, VATS with bullectomy/pleurectomy is the recommended first line therapy for its low recurrence rates and low morbidity. ^{50 51 52} If the patient's prognosis is poor, surgery is contraindicated, or patients wish to avoid it, catheter based talc pleurodesis is appropriate. ⁴⁷

Overview of Types of Sclerosants

Talc, hydrated magnesium silicate, is the most effective agent for pleurodesis of recurrent pleural effusion. Medical talc is sterilized and free of asbestos. The currently available larger particle talc is thought to reduce risk of systemic absorption. ²⁸ Several meta-analysis concluded that pleurodesis with talc was more successful in studies comparing it to bleomycin, povidone iodine, doxycycline, tetracycline, silver nitrate or drainage alone, making it the sclerosant of choice. ^{54 55} Talc also has the added benefit of lower cost per treatment when compared to other agents. ⁵⁶ Tetracycline was a popular choice until production of parenteral tetracycline ceased, and clinicians opted for other alternatives such as doxycycline, minocycline, bleomycin and talc. ^{28 46 53 57} Studies in animal models had demonstrated exuberant pleural adhesions on autopsy after treatment with tetracycline, ^{58 59} however, decreased production and reports of systemic side effects have caused its use to wane. ^{60 61} After tetracycline was discontinued, clinicians turned to doxycycline as an alternative. ⁶² Studies have shown talc is superior to doxycycline. Doxycycline has high rates of intraprocedural pain and systemic effects such as hepatotoxicity causing it to fall out of favor. ^{39 63 64}

Technique

Mild coagulation abnormalities are not an absolute contraindication to an ultrasound-guided pleural intervention, but more serious blood diathesis should be corrected. ⁶⁵ Relative contraindication includes INR > 1.5 and platelets < 50,000, as well as ongoing anticoagulation therapy. ⁶⁶ Local intrapleural lidocaine injection and moderate sedation help to relieve patient discomfort and anxiety. ⁶⁶

Prior to treatment, initial thoracentesis should be performed to exclude the presence of loculations or trapped lung. ³⁴ While thoracentesis can be performed without image-guidance, ultrasound-guidance enhances procedural success and reduces the need for future procedures. ⁶⁷

Techniques for thoracentesis are described in the previous article in this issue.

Thoracostomy Tube Placement

Prior to catheter directed pleurodesis a thoracostomy tube needs to be placed. The patient should be positioned in a sitting position to allow for fluid to collect dependently and for maximum drainage. Alternatively, the patient can lie supine if this is not tolerated. Needle placement under ultrasound visualization ( Fig. 2a ) reduces complications such as hemothorax, pneumothorax, and accidental penetration into the abdominal cavity. ^{68 69 70 71} The target location of entry should be free of wounds or other infection. In relation to the ribs, the needle should enter lateral to the angle of the rib, along the posterior axillary line, and traverse the top of the rib to avoid hitting the intercostal neurovascular bundle at the 6-7 ^th intercostal space. ⁶⁵ Catheter placement laterally is optimal as the ribs are spaced more widely and there is less risk to neurovascular bundles. There is also less likelihood that the catheter will kink when the patient is supine. ⁷²

Fig. 2.

( a ) Using ultrasound guidance, an 18-gauge needle was advanced into the pleural space at the 6-7 ^th intercostal space at the midaxillary line. Intrapleural fluid was aspirated and collected for clinical samples as requested. ( b, c ) Under fluoroscopy, the 0.035-inch Amplatz Super Stiff™ guidewire (arrow) was advanced through the needle over the top of the 7 ^th rib and guided into the region of the apex. The needle was exchanged over the wire with serial tissue dilators (not pictured). The dilators were inserted approximately 1 cm into the pleura only, to avoid potential parenchymal damage. ( d ) A 10-Fr locking pigtail chest catheter (arrow) was advanced into the pleural space, and the wire and inner stiffener were removed to form and lock the pigtail. The pigtail catheter was then used to instill the sclerosant mixed in saline. The chest tube was clamped for several hours to allow the sclerosant to distribute in the pleural space. Then the catheter was unclamped and set to gravity drain.

The skin should be cleansed and prepped in a standard sterile technique. Local anesthetic is applied at the dermal layer of the skin and the pleural layer, which are the highly innervated zones. An 18-gauge Chiba (Cook Medical LLC, Bloomington, IN), Hawkins™ (Argon Medical Devices, Frisco, TX), or Yueh Centesis Catheter Needle (Cook Medical LLC, Bloomington, IN) 0.035-inch Amplatz Super Stiff™ (Boston Scientific, Marlborough, MA) guidewire to pass ( Fig. 2b ). Fluid is aspirated and collected for any clinical samples as needed. Then the guidewire is passed through the cannula prior to its removal ( Fig. 2c ). A skin nick is made at the entry site to allow for the series of dilators to be passed through, widening of the tract. It is important to avoid over-exuberant insertion of the dilator over 1 centimeter (cm) beyond the pleural edge as serious visceral injury can occur. The 10- 12 French (Fr) Multipurpose Drainage Catheter (Cook Medical LLC, Bloomington, IN) is then inserted over the wire, with the catheter drainage pore approximately 5-10 cm beyond the pleural edge and the pigtail lying within the dependent costophrenic sulcus ( Fig. 2d ). ⁶⁵ Typically catheter suction is not necessary, however low pressure suction can be used if needed. ²⁸

Talc Pleurodesis

Sterile talc slurry is a mixture of 4-5 grams (g) of sterile talc in 50 to 100 cubic centimeters (cc) of sterile saline and 10 cc of lidocaine. ⁶⁶ Prior to administration, the mixture should be shaken vigorously. Once the effusion is fully drained, the sclerosant is administered and the intercostal tube should be clamped for at least 1-2 hours after sclerosant is administered to allow for sclerosant distribution, though some centers report clamping for up to 4-6 hours. ⁷³ Some centers rotate the patient every 15 minutes to distribute the sclerosant within the pleural cavity. However, this can be uncomfortable for patients, risks catheter dislodgement and studies have shown it is ineffective, ²⁸ therefore, it is not recommended. The tube should be reattached to gravity drainage for evacuation of the effusion. ^{28 35} A post-procedure chest radiograph should be obtained to confirm effusion drainage and lack of pneumothorax to establish a baseline. Standard chest tube principles apply regarding catheter removal when drainage falls below 150 cc per day. If there is persistent dyspnea and residual radiographic pleural effusion, attempt repeat pleurodesis and leave the indwelling pleural catheter in place. ²⁸ Pleurodesis failure may be due to trapped lung and leaving a tunneled pleural catheter in place can manage dyspnea and may achieve autopleurodesis over time. ⁷⁴

If loculations are present, attempts can be made to disrupt them by administering intrapleural tissue plasminogen activator (tPA) to break up the fibrin. Typically, 2 to 4 mg of tPA such as alteplase (Activase ^® Genentech, San Francisco, CA) is administered in 10 to 20 mL saline via the chest tube and repeated every 8 hours for up to 3 days. Additionally, 5 mg of deoxyribonuclease (DNase) dornase alfa (Pulmozyme ^® Genentech, San Francisco, CA) can be used every 12 hours for 3 days to increase enzymatic lysis of fibrin. ⁷² Combining tPA and DNase has the highest efficacy according to the MIST2 study. ⁴⁰ After administration the tube is clamped for up to 2 hours, then set back on drainage. ⁷³

Needle Aspiration and Pigtail Catheter Placement for Pneumothorax

Initially, small pneumothoraxes are treated with needle aspiration. The patient lies supine, and the chest wall is sterilized at the level of the 2 ^nd and 3 ^rd intercostal space at the midclavicular line. The air is aspirated with an 18-guage needle, then a 0.035-inch Amplatz Super Stiff™ (Boston Scientific, Marlborough, MA) guidewire is passed through the needle and towards the apex, followed by an 8.5-12 Fr Multipurpose Pigtail Drainage Catheter (Cook Medical LLC, Bloomington, IN) , with the pigtail lying at the anterior lung apex. ⁷³ The tube can be connected to a standard water-seal using a Pleura-evac device ^® (Teleflex, Morrisville, NC) or Heimlich valve, which is a one-way flutter valve that prevents intrapleural air from reaccumulating via the chest tube. ⁷⁵ Follow up chest radiograph after the procedure should confirm re-expansion. Prior to removing the catheter, it should be clamped, and there should be no evidence of recurrent pneumothorax on a subsequent 2-hour post chest radiograph. ^{46 73}

The main difference in technique for pleurodesis in cases of spontaneous pneumothorax is to avoid clamping the tube after instilling the talc slurry. Instead, the tube should be kept on gravity drainage/ water seal to avoid developing a tension pneumothorax. ^{49 76}

Complications and Management

Chemical pleurodesis is a generally safe and well-tolerated procedure with few complications. However, there are several side effects and complications that interventionalists should be aware of, as well as methods to ameliorate or prevent them.

Complications of Thoracentesis and Catheter Drainage

Pain at the catheter site is a frequently reported side effect of TPC placement reported in about one third of patients. It often resolves in a matter of days with oral pain management. ¹³ Severe pain requiring catheter removal occurs in less than 1% of cases. ¹³ Catheter occlusion occurs in roughly 2 - 5% of patients. ^{13 77} The majority of cases can be resolved with 2-4 mg dose of tPA diluted in 10-20 cc of saline administered in the tube and clamped for a 1 to 2 hours after which the catheter is again allowed to drain. This can be repeated three times a day for several days. ^{73 78 79} Catheter dislodgement rates are variable, ranging from 1–18% of cases. ⁷⁷

Local cellulitis is another common complication, occurring in about 5% of patients. ^{13 77 80} Most of these patients can be successfully treated with antibiotics, although for the majority of patients, this may involve hospitalization and/or IV antibiotics. ⁸⁰ If the infection appears localized to the skin, it can be treated with a 10-day course of empiric oral antibiotics with MRSA coverage. ¹³ Deeper infection such as empyema tends to be less common with sterilized medical-grade talc usage. ⁴³ TPC associated empyema is treated with catheter drainage, IV antibiotics and tPA fibrinolysis administration via catheter. ^{13 17}

Symptomatic re-expansion pulmonary edema (RPE) is a rare complication of large-volume thoracentesis occurring in less than 1% of cases, and does not appear to be correlated to the volume removed. ⁶⁸ Traditionally, 1- 1.5 liters (L) is cited as an arbitrary upper limit for thoracentesis. However, studies have questioned that paradigm as RPE is a rare occurrence not associated with absolute change in pleural pressure. A study suggests that more than 1.5 L of fluid may be removed as long as patients tolerate the procedure. ⁶⁸ RPE is treated with diuresis and supplemental oxygen. Advanced noninvasive ventilation or intubation may be necessary.

Pneumothorax is a known complication of catheter placement. The suspected pathophysiology is due to nonuniform stress over the pleura during drainage causing a transient changes in pressure, rather than direct lung injury. ⁸¹ Reports of complications such as pneumothorax or bronchopleural fistula formation, which is a persistent communication between the pleura and bronchioles, are around 3%. ¹² Ultrasound guidance has been shown to reduce post-procedure pneumothorax. ⁸² If a pneumothorax is suspected after intraprocedural aspiration of air during fluid drainage, post-procedure chest radiograph can confirm the diagnsosis. ⁶⁵ Treatment is decompression via the thoracostomy tube.

Local bleeding occurs in 1- 3% of cases, usually during catheter insertion or removal, and included events such as local hematoma. ^{12 77} More serious cases of bleeding can be avoided by correcting severe bleeding diathesis and avoiding procedures in severely thrombocytopenic patients when possible. Additionally, chest tubes are placed over the superior aspect of the rib to reduce rates of intercostal artery injury which may cause life-threatening hemothorax. Of note, there is increased risk of injury in older patients due to increasing tortuosity of the intercostal arteries. ⁶⁵ Suspected injury can be confirmed on angiography, and can be subsequently treated percutaneously with embolization using particles, coils, or liquid embolic agents, sometimes in combination. ⁶⁵

Complications of Talc Pleurodesis

Pleuritic chest pain is the most common side effect associated with pleurodesis, reported in 25–50% of patients. ^{83 84 85} Smaller caliber chest tubes/ pleural catheters tend to be associated with less pain. ^{29 78} Treatment includes non-steroidal anti-inflammatory drugs (NSAIDS) and opioids if pain is severe. There is no reduction in level of inflammatory pleural symphysis development with the use of NSAIDS, as had been once suspected. ^{78 79} Unexplained fever is another common complication, occurring in 26 to 60% of patients undergoing talc pleurodesis. ^{83 85} This is likely due to systemic inflammatory response of the sclerosant. ⁸⁶

A rare but serious complication is acute respiratory distress syndrome (ARDS) due to systemic absorption of talc particles from the intrapleural lymphatics. Reported rates as high as 9% are mainly in studies using small particle talc. ⁸⁵ It is virtually unreported in larger particle talc. ^{84 87 88} Studies also report rates of sudden death immediately or shortly after talc pleurodesis, due to cases of massive pulmonary embolism, heart failure, and electrolyte abnormalities. ⁸⁹ Development of pulmonary embolism is thought to be due to systemic uptake of talc sclerosant leading to activation of the inflammatory cascade and a thrombogenic state, in addition to underlying comorbidities such as malignancy. ⁸⁹

Pleurodesis failure is hard to predict. It is usually due to trapped lung or loculated pleural effusion, which may necessitate alternate interventions such as fibrinolytics, TPC placement or VATS decortication. ^{28 34} Many studies recommend attempting repeat pleurodesis or switching to TPC placement to attempt autopleurodesis. ⁹⁰

Conclusion

Pleural space diseases including refractory effusions and recurrent spontaneous pneumothoraxes pose a significant symptomatic burden on patients and can incur multiple interventions and hospital visits for patients. The goal for interventional therapies for both types of disease is to achieve pleurodesis by remove the interdigitating air or fluid, and induce fibrosis that can lead to complete pleural symphysis, thereby minimizing symptoms of dyspnea, improving quality of life, and obviating the need for further procedures. While traditionally pleurodesis was performed with a variety of chemical agents via open thoracotomy or VATS, there is a push towards minimally invasive catheter directed therapies with or without the use of talc, which is currently deemed the most effective sclerosant.

Much of the literature focuses on the treatment of recurrent malignant pleural effusions. Emerging research has shown that there are similar rates of efficacy between thoracoscopic talc poudrage and chest tube talc slurry pleurodesis in treating MPE. ³⁸ Additionally, studies have demonstrated that isolated tunneled pleural catheter drainage offers similar symptom relief as catheter based pleurodesis using talc. There is an added benefit of fewer total hospitalization days and future interventions with TPC. ^{29 30} Without the use of a chemical sclerosant such as talc, TPC drainage results in autopleurodesis in approximately one half of cases. ^{12 27 29} This is presumably because pleural irritation stemming from repeat drainage and the presence of the catheter itself causes fibrosis. ¹³ However, a caveat is that TPC drainage requires greater supportive home health services for patients to be able to maintain this treatment, which may take several months to achieve autopleurodesis. ^{27 77} Moreover, the catheter may be permanent, given the overall poor prognosis of patients who progress to malignant effusions. Given these factors, catheter based pleurodesis with talc is an alternative therapy to achieve symptom relief without the need for an indwelling catheter. It is important to involve patients in weighing this decision given the various advantages and disadvantages of these treatment options. ^{29 30}

Studies on catheter-based talc pleurodesis of recurrent transudative effusions are fewer and less robust, but hint at high rates of pleurodesis. TPC autopleurodesis rates in these patients are variable, indicating the need for additional large-scale studies. ⁵ Futures studies should also investigate the utility of combining the two treatments, pleurodesis via indwelling pleural catheter in the setting of transudative and exudative effusions.

Lastly, the most effective treatment for preventing recurrent primary spontaneous pneumothorax continues to be surgical intervention, with the lowest rates of recurrence after surgical bullectomy or pleurectomy. Current literature and expert panels have determined that chest tube pleurodesis is only indicated in nonsurgical candidates or those who refuse surgery, and in treating post-operative persistent air leak. ^{46 51} Additionally, chest tube pleurodesis is also indicated in preventing secondary spontaneous pneumothorax, as this demographic of patients is a higher surgical risk. ^{53 76} However, further large-scale studies are indicated to better characterize the role of catheter based pleurodesis against VATS pleurectomy.