Pleurodesis

Anatomy and Physiology

Pleurodesis involves the pleural cavity, a potential space between the parietal and visceral pleura that normally contains a small amount (10–20 mL) of lubricating fluid. This fluid facilitates smooth lung movement during respiration. The parietal pleura lines the thoracic cavity, diaphragm, and mediastinum, while the visceral pleura covers the lungs. Both pleural layers comprise mesothelial cells supported by a connective tissue matrix containing blood vessels, lymphatics, and nerve fibers.

Under normal conditions, pleural fluid production and absorption are balanced, resulting in no net accumulation.[6] This balance is maintained through capillary filtration, mesothelial secretion, and lymphatic drainage. However, numerous pathological conditions, such as malignant pleural effusions or pneumothorax, disrupt this equilibrium, leading to fluid or air accumulation within the pleural cavity.[7] This impairs lung function and causes symptoms such as dyspnea, necessitating intervention.

Pleurodesis aims to obliterate the pleural cavity by inducing adhesions between the pleural layers, eliminating potential space. Chemical agents (eg, talc) or mechanical abrasions cause mesothelial injury and trigger an inflammatory cascade. Cytokines, growth factors, and inflammatory cells (eg, neutrophils and macrophages) drive fibrin deposition and fibroblast activation, leading to fibrous adhesions. These adhesions tether the pleural surfaces, preventing the reaccumulation of fluid or air. The success of pleurodesis depends on intact mesothelial function and an adequate inflammatory response to achieve adhesion formation. Understanding the intricate anatomy and physiology of the pleural space and the pathological mechanisms disrupting normal pleural fluid dynamics is essential for optimizing pleurodesis techniques and improving patient outcomes.

Indications

The most common indication for pleurodesis is a malignant pleural effusion, often refractory to standard management.[8] Pleurodesis effectively prevents the reaccumulation of fluid in these patients, alleviating symptoms such as dyspnea and improving quality of life. Other key indications include recurrent pleural effusions, malignant or nonmalignant, and recurrent or persistent pneumothorax.[8] While numerous management options exist for these conditions, pleurodesis should be undertaken only after thorough patient discussions, ensuring alignment with their expectations and clinical goals. A medical pleurodesis is generally preferred, particularly for patients unsuitable for surgical intervention.

Chemical pleurodesis is indicated for malignant pleural effusions, refractory symptomatic nonmalignant effusions (eg, associated with chylothorax, hepatic hydrothorax, nephrotic syndrome, or heart failure), recurrent primary pneumothorax, and recurrent secondary pneumothorax.[1][7] In contrast, mechanical pleurodesis addresses similar indications but offers the advantage of simultaneous management of the underlying pathology. For instance, during VATS, surgeons can perform pleurodesis while resecting subpleural blebs or bullae, which may be the source of recurrent pneumothorax. By eliminating the pleural space, pleurodesis reduces recurrence risk and improves long-term outcomes.

Contraindications

Pleurodesis is contraindicated in several clinical scenarios, particularly when the underlying condition or patient factors impede the procedure's success or pose significant risks. A nonexpandable lung (NEL), commonly seen in patients with malignant pleural effusion due to lung entrapment, is a major contraindication. NEL often arises from endobronchial obstruction or malignant involvement of the visceral pleura, preventing the visceral and parietal pleura apposition following fluid drainage from the pleural space.[9] Indicators of NEL include hydropneumothorax after thoracentesis, inability to fully evacuate pleural effusion, severe coughing, or central chest pain during fluid aspiration. In such cases, the lung's inability to expand increases the negativity of pleural pressure, perpetuating the transudation of fluid from the parietal pleural capillaries and leading to recurrent effusions. This condition can significantly diminish patients' quality of life. A lack of awareness of lung entrapment may result in unnecessary or ineffective treatments, potentially causing considerable morbidity.[10] For patients with malignant lung entrapment, management strategies such as intermittent pleural drainage or an indwelling pleural catheter have shown greater efficacy.[11]

Successful pleurodesis requires contact between the pleural layers; thus, any disease process interfering with complete lung expansion (eg, trapped lung, insufficient drainage) would lead to pleurodesis failure.[12] Pleural manometry at the time of therapeutic thoracentesis can help identify unexpandable lungs. Manometry measures pleural pressure changes as pleural fluid is withdrawn and allows the calculation of pleural elastance at the end of the procedure. A final value for pleural elastance greater than or equal to 19 cm/H₂O/L of fluid removed indicates a high likelihood of an unexpandable lung and predicts pleurodesis failure.[1] Hence, medical pleurodesis is generally contraindicated in such patients, and mechanical pleurodesis is preferred. Individual exceptions may apply to patients with very small loculated pneumothoraces or who decline mechanical pleurodesis.

Other risk factors for unsuccessful pleurodesis include previous thoracic irradiation and a chest tube duration of more than 10 days, while risk factors for death included a Karnofsky index of less than 50%, a body mass index less than 25 kg/m², malignancy, and male sex.[13] Patients with a life expectancy of less than 3 months should not be treated with pleurodesis but instead should be treated with repeated thoracentesis as required to relieve dyspnea.[14] Other contraindications include active pleural infections (eg, empyema), severe coagulopathy, significant patient instability, the lack of patient consent, and more than 150 mL of fluid output through the chest drain.

Equipment

Medical pleurodesis has traditionally been performed by instilling substances into the pleural cavity that induce inflammation, leading to sclerosis and adhesions between the parietal and visceral pleura. An ideal sclerosing agent would be cost-effective, widely accessible, easy to administer, highly effective at achieving pleurodesis and associated with minimal side effects.[15] Despite extensive research, no single agent perfectly meets these criteria. Over time, various agents such as autologous blood, doxycycline, iodopovidone, Streptococcus pyogenes A3 (OK-432), and silver nitrate have been utilized.[16] Talc is widely regarded as the most effective and safest option in the current literature. Talc pleurodesis has demonstrated success rates ranging from 80% to 95%, influenced by factors such as dosage, frequency of application, the underlying condition, and the patient's overall health. While other agents are generally effective, none have shown superiority over talc.[15]

Following are the sclerosing agents that can be used as chemicals for chemical pleurodesis:

• Talc
• Tetracyclines (minocycline, doxycycline)
• Silver nitrate
• Iodopovidone
• Bleomycin
• Corynebacterium parvum with parenteral methylprednisolone acetate
• Erythromycin
• Fluorouracil
• Interferon beta
• Autologous blood
• Mitomycin C
• Cisplatin
• Cytarabine
• Doxorubicin
• Etoposide
• Bevacizumab (intravenous or intrapleural)
• OK-432

In addition to selecting the appropriate pleurodesis agent, the choice of chest tube size remains a topic of debate. Smaller chest tubes (<16 Fr) are preferred over larger ones for drainage and pleurodesis. This recommendation is based on evidence suggesting that smaller tubes result in smaller incisions and cause less pain during and after insertion. However, a meta-analysis of 4 prospective randomized controlled trials provided results showing comparable success and complication rates between small-bore and large-bore chest tubes for delivering sclerosing agents. However, findings from the TIME1 trial indicate that larger tubes may be more effective than smaller ones (<12 Fr) in achieving successful pleurodesis.[17]

The choice among these agents is determined by several factors, including local expertise, availability of individual agents, and the underlying process for which chemical pleurodesis is needed. The sclerosing agent is delivered via a chest tube, varying from a large bore (eg, 24 Fr) to a small bore (eg, 12 Fr) into the pleural cavity. The other equipment required for pleurodesis besides the sclerosing agent include:

• A patent intercostal drain with a 3-way stopper attached
• 25 mL of 1% lidocaine injection
• Sterile gloves
• 50 mL of sterile saline
• 50 and 20 mL syringes
• Premedication with some analgesic other than nonsteroidal anti-inflammatory drugs (NSAIDs)

Personnel

While pulmonologists can perform medical pleurodesis at the bedside under local anesthesia, mechanical pleurodesis is performed under general anesthesia during open thoracotomy or VATS in an operating room by a thoracic surgeon.

Preparation

Proper preparation for pleurodesis is essential to optimize outcomes, minimize complications, and ensure patient safety. The process begins with thorough patient selection and evaluation. Informed consent from the patient should be obtained with an explicit discussion of the procedure's indications, alternatives, risks, and complications. The procedural site should be marked, and the status of nil per os should be confirmed. Team preparation involves ensuring the availability of necessary equipment, including chest tubes, sclerosants, and imaging tools, as well as confirming the readiness of the multidisciplinary team. An appropriate plan for sedation and anesthesia should be established. For chemical pleurodesis, a patent chest tube should be in situ, the lung should be expanded to the chest wall, and fluid output from the chest drain should be less than 100 mL in the last 24 hours. 

Technique or Treatment

The approach to pleurodesis varies significantly among centers and practitioners, with differences in the type of pleurodesis, sclerosing agent, chest tube size, and choice of analgesia. Chemical pleurodesis using talc, either as talc slurry administered through a chest tube or talc poudrage delivered thoracoscopically, remains a common method. Small-bore chest tubes are generally preferred due to better patient tolerance, and analgesia often involves either opioids or NSAIDs for pain management.[18] Alternative approaches include the thoracoscopic administration of talc by poudrage or large-bore chest tubes for talc slurry and thoracoscopic mechanical pleural abrasion followed by drainage with a large-bore chest tube. These methods also demonstrate efficacy in achieving pleurodesis and may be tailored based on patient needs, disease characteristics, and institutional expertise.

Chemical Pleurodesis

Chemical pleurodesis involves obliterating the pleural space by inducing inflammation and fibrosis with a sclerosant, most commonly talc. Sclerosants can be instilled via small- or large-bore chest tubes or indwelling catheters as talc slurry, administered thoracoscopically, or via thoracotomy as talc insufflation/poudrage. Among these methods, chemical pleurodesis with a small-bore chest tube is generally preferred due to its comparable efficacy, lower invasiveness, and better patient tolerance.[7]

Talc, primarily composed of hydrated magnesium silicate, is inexpensive and readily available, with a recommended dose of up to 10 g. Talc elicits a robust inflammatory response by producing cytokines and adhesion molecules like interleukin 8, vascular endothelial growth factor, and transforming growth factor beta. Other sclerosants, including doxycycline (80% success rate), bleomycin, silver nitrate, and povidone-iodine, are less commonly used.[19] The choice of method and agent depends on patient circumstances, goals, and institutional practices. VATS may be indicated for diagnostic purposes or in patients needing thoracoscopic intervention, while chest tube administration is preferred for cardiopulmonary compromise patients.[7]

Small-bore chest tubes (eg, 12 Fr) are typically favored over large-bore tubes (eg, 24 Fr) as they are equally effective and cause less patient discomfort. Study results show comparable pleurodesis success rates at 3 months between small- and large-bore tubes, with significantly lower pain scores in patients using smaller tubes.[20] Given the high density of pain receptors in the parietal pleura, intrapleural sclerosant instillation is often painful, necessitating effective analgesia. To manage this, clinicians commonly prescribe NSAIDs or opioids. While animal studies suggest NSAIDs might reduce pleurodesis efficacy, clinical evidence demonstrates comparable failure rates between NSAID use (eg, ibuprofen 800 mg 3 times daily) and opioid use (eg, 10–20 mg oral morphine 4 times daily), with rates of 23% and 20%, respectively.[17][21] The choice of analgesic is tailored to the patient, considering pain severity, sensitivities, history of gastrointestinal bleeding, opioid dependency, renal or hepatic dysfunction, and life expectancy.

The procedure for chemical pleurodesis is as follows: 

• The procedure for instilling a sclerosant for pleurodesis begins with sterile preparation. Wear sterile gloves and clean the chest tube and surrounding area with povidone iodine or another sterilizing agent. Position a sterile dressing beneath the chest tube and 3-way stopper. Remove the cap from the chest tube and clean it with the 3-way stopper. Prepare 1% lidocaine in a syringe, attach it to the 3-way stopper, and instill the lidocaine into the pleural cavity to provide local anesthesia. Remove the syringe and turn off the stopper.
• Next, prepare the sclerosant slurry by mixing the agent (eg, talc) with 40 mL of normal saline in a 50 mL syringe. Shake well, as talc is difficult to dissolve, and keep the syringe moving continuously to prevent precipitation. Instill the prepared slurry into the pleural cavity via the chest tube and flush it immediately with 10 mL of normal saline to ensure delivery. Close the 3-way stopper and keep it closed for 3 hours to allow the sclerosant to act effectively.

After pleurodesis, additional analgesia may be necessary to manage pain; however, NSAIDs should generally be avoided as they can inhibit the inflammatory response required for effective pleurodesis. After 3 hours, the chest drain should be reopened to resume drainage. A chest radiograph should be obtained 24 hours postprocedure to confirm the absence of pneumothorax or fluid reaccumulation. The chest tube can be safely removed if the radiograph is satisfactory and there is no further fluid output. Follow-up, including a chest radiograph, is recommended after 4 to 6 weeks to assess the procedure's success and ensure patient stability.

Pleurectomy

Pleurectomy involves the radical resection of the visceral and parietal pleura (total or subtotal) and may include decortication, which removes a fibrous pleural rind. This procedure can be employed to control malignant pleural effusions in cases where chemical pleurodesis has failed. Pleurectomy and decortication may also serve as primary therapeutic options for patients with malignant pleural effusions due to mesothelioma. However, these interventions do not improve overall survival and are associated with significant complications. Given the invasiveness and morbidity of this thoracotomy-requiring procedure, it is reserved for patients with good surgical candidacy and a reasonably prolonged life expectancy.

Mechanical Pleurodesis

Mechanical pleurodesis induces pleural adhesion through physical abrasion of the pleural surfaces, typically during thoracoscopy or thoracotomy. This method is primarily used for recurrent pleural effusions, pneumothoraces, or in conjunction with procedures for malignant pleural effusion. Below is an overview of the technique:

• For thoracoscopy, a thoracoscope is inserted through one or more small incisions, while thoracotomy requires a larger incision to expose the pleural cavity. Any pleural fluid or air is removed to collapse the lung partially, improving visibility and access to the pleural space. The pleural cavity is then carefully inspected for lesions, adhesions, or abnormalities. During mechanical abrasion, a sterile surgical pad, gauze, or specialized pleural abrader gently rubs the parietal pleura, creating uniform abrasions. This induces an inflammatory response that promotes the release of cytokines and fibrin deposition, leading to pleural adhesion and fibrosis. Care must be taken to avoid damaging underlying structures, such as the intercostal nerves and blood vessels. After ensuring adequate abrasion, the pleural cavity is inspected for complications like bleeding or lung injury. The lung is then reexpanded to its full volume to ensure contact between the visceral and parietal pleura, facilitating adhesion formation.
• A small-bore chest tube is inserted to drain any remaining pleural fluid or air and is typically left in place until fluid output is minimal and pleural adherence is confirmed.
• Tunneled pleural catheter placement is a highly effective palliative strategy for managing malignant pleural effusion, offering significant symptom relief while facilitating outpatient care. The minimally invasive nature of this catheter and the low complication risk make it an optimal choice for patients with malignant pleural effusion, particularly those with limited life expectancy or recurrent effusions. Tunneled pleural catheter insertion should be considered a primary treatment option for these patients to enhance quality of life and minimize hospital stays.[22]

Postprocedure Care

After pleurodesis, additional analgesia may be necessary to manage pain; however, NSAIDs should generally be avoided as they can inhibit the inflammatory response required for effective pleurodesis. After 3 hours, the chest drain should be reopened to resume drainage. A chest radiograph should be obtained 24 hours postprocedure to confirm the absence of pneumothorax or fluid reaccumulation. The chest tube can be safely removed if the radiograph is satisfactory and there is no further fluid output. Follow-up, including a chest radiograph, is recommended after 4 to 6 weeks to assess the procedure's success and ensure patient stability.

Complications

Pleurodesis, while effective for managing recurrent pleural effusions and pneumothoraces, carries risks of complications and variable success rates influenced by patient factors, tumor characteristics, and procedural nuances.

Complications of Pleurodesis

• Pain and inflammation
  • Pleural inflammation induced by chemical agents or mechanical abrasion can cause significant chest pain, often requiring NSAIDs or opioids.
  • Fever is a common inflammatory response.
• Infection
  • Failure to maintain an aseptic technique can result in pleural infection or empyema.
• Respiratory complications
  • Potential complications include pneumothorax, hemothorax, reexpansion pulmonary edema, and acute respiratory distress syndrome (ARDS). Due to systemic absorption, ARDS has been reported with talc use, especially when smaller talc particles or large doses are administered.[23][24]
• Systemic effects
  • Systemic inflammation, coagulation cascade activation, and pulmonary embolism have been documented, particularly with chemical pleurodesis.[25][26]
    • Systemic inflammation has been reported in patients receiving talc.[23] 
• Failure of pleurodesis
  • Trapped lung, inadequate lung expansion, or insufficient inflammatory response may lead to procedural failure.
    • Failure of the procedure may be due to increased tumor burden, which causes a decrease in the mesothelial cells and, therefore, an inadequate inflammatory response.[27] 
    • The type of tumor may also play a role in the process; diffuse mesothelioma and metastatic carcinomas have an inadequate response. This is because the healthy mesothelial cells secrete the inflammatory mediators necessary for fibrosis.[27]
• Surgical complications
  • Surgical pleurodesis carries risks related to general anesthesia, wound infection, and atelectasis.

Factors Influencing Success

The success of pleurodesis depends on several factors, including the tumor burden, type of malignancy, and biochemical characteristics of pleural fluid. A decrease in mesothelial cells, often seen in diffuse mesothelioma or metastatic carcinomas, impairs the secretion of inflammatory mediators necessary for fibrosis. Biochemical parameters such as pleural fluid pH and glucose levels are critical predictors of success. In a study, results showed that patients with pleural fluid pH below 7.20 experienced a 43% failure rate, compared to 9% in those with higher pH. Low pleural fluid glucose and pH levels were associated with significantly shorter survival (1.9 vs 5.7 months).[28] Tumor type further influences outcomes; for example, those with breast cancer had longer median survival (7.4 months) compared to those with chemotherapy-resistant cancers (4.7 months). Careful patient selection, meticulous procedural technique, and tailored approaches based on individual patient factors are essential to optimize outcomes and minimize complications. Regular postprocedure monitoring is crucial for early detection and management of adverse events.

Clinical Significance

Pleurodesis is a critical therapeutic intervention for managing recurrent pleural effusions and pneumothoraces, significantly impairing respiratory function and quality of life. The primary clinical significance of pleurodesis lies in its ability to obliterate the pleural space, thereby preventing the recurrent accumulation of air or fluid that causes dyspnea, chest pain, and respiratory distress. Pleurodesis effectively palliates malignant pleural effusions, reducing the need for repeated thoracenteses and improving functional status. This procedure is particularly valuable in advanced malignancies, where symptom management is a priority. However, its success is influenced by pleural fluid pH, glucose levels, tumor burden, and underlying lung expansion capacity.

Pleurodesis offers a definitive solution for recurrent pneumothorax, especially in high-risk patients or those unfit for more invasive surgical interventions. Chemical and mechanical pleurodesis are viable options, and patient characteristics, preferences, and institutional expertise guide the choice. Pleurodesis also has a role in select nonmalignant conditions, such as chylothorax and hepatic hydrothorax, where recurrent effusions are refractory to medical management. By addressing the underlying pathology and preventing recurrence, pleurodesis alleviates symptoms and reduces healthcare utilization, including hospitalizations and invasive procedures. Thus, it is a cornerstone in the management of pleural diseases.

Enhancing Healthcare Team Outcomes

Effective pleurodesis requires a collaborative, interprofessional approach to ensure patient-centered care, optimal outcomes, safety, and seamless team performance. Clinicians play a pivotal role in decision-making, procedural execution, and tailoring the approach to individual patient needs, including selecting sclerosing agents, procedural techniques, and analgesia. Their clinical skills and strategy are bolstered by thorough patient evaluation, accurate diagnosis, and integration of evidence-based guidelines. Nurses ensure proper pre and postprocedure care by monitoring the patient’s vitals, managing chest tubes, and providing education on postprocedural expectations and signs of complications.

Pharmacists contribute by advising on appropriate analgesics and managing potential drug interactions, particularly in patients with complex medical histories. Effective interprofessional communication is crucial; team members must share real-time updates on patient status, coordinate care plans, and address complications. Care coordination includes scheduling follow-ups, ensuring access to imaging, and collaborating on rehabilitation or palliative care when necessary. This team-based approach promotes patient safety, enhances procedural success, and improves overall patient satisfaction by addressing clinical and psychosocial needs.