Chemical pleurodesis for the prevention of recurrent pleural effusion

INTRODUCTION — Pleurodesis is a procedure that obliterates the pleural space to prevent recurrent pleural effusion. It is most commonly performed by inducing intrapleural inflammation, with consequent fibrin deposition and scarring by either instilling a chemical irritant or performing mechanical abrasion. The use of a chemical irritant is known as chemical pleurodesis.

The indications, contraindications, preparation, choice of sclerosant, procedure, and complications of chemical pleurodesis to prevent pleural effusion will be reviewed here. The techniques of tube thoracostomy and pleural abrasion during thoracoscopy are discussed separately. (See "Thoracostomy tubes and catheters: Indications and tube selection in adults and children" and "Pneumothorax: Definitive management and prevention of recurrence".)

CLINICAL APPLICATIONS AND CONTRAINDICATIONS

Clinical applications — Chemical pleurodesis has been used to prevent recurrence of both malignant and nonmalignant pleural effusion, the details of which are discussed in separate topic reviews:

●(See "Management of malignant pleural effusions", section on 'Pleurodesis (alternative to IPC or failed IPC)'.)

●(See "Management of nonmalignant pleural effusions in adults".)

The indications for and techniques of pleurodesis for patients with pneumothorax are discussed in detail elsewhere. (See "Treatment of secondary spontaneous pneumothorax in adults", section on 'Preventing recurrence and follow-up' and "Treatment of primary spontaneous pneumothorax in adults", section on 'Prolonged air leak' and "Treatment of primary spontaneous pneumothorax in adults", section on 'Recurrence' and "Treatment of primary spontaneous pneumothorax in adults", section on 'Indications for definitive procedure after first event' and "Pneumothorax: Definitive management and prevention of recurrence".)

Contraindications — Contraindications to pleurodesis are similar to those for thoracentesis (eg, severe and uncorrectable bleeding diathesis, infection at the chest tube or thoracoscopic insertion site) with the added contraindications of nonexpandable lung [NEL] and untreated intrapleural infections. (See "Diagnostic evaluation of the hemodynamically stable adult with a pleural effusion", section on 'Contraindications'.)

●NEL – Pleurodesis will fail if the lung cannot fully expand to the chest wall (eg, tumor encasement of lung, interstitial pulmonary fibrosis, endobronchial obstruction) because successful pleurodesis requires apposition of the visceral and parietal pleural surfaces. Chemical pleurodesis should therefore not be attempted when the lung does not fully expand after therapeutic thoracentesis or chest tube drainage of fluid. Identifying NEL is discussed separately. (See "Diagnosis and management of pleural causes of nonexpandable lung".)

●Untreated pleural infections – We do not attempt pleurodesis if we suspect an untreated parapneumonic effusion or empyema. Infection in the pleural space should be treated first before attempting pleurodesis. (See "Management and prognosis of parapneumonic pleural effusion and empyema in adults".)

PREPROCEDURE PREPARATION — Success of chemical pleurodesis is largely dependent upon the induction of significant inflammation to achieve adequate fibrosis and obtaining proper apposition of the visceral and parietal pleural surfaces before and after the procedure. If feasible, we limit medications that may interfere with the inflammatory effect of the sclerosant or increase the risk of pleural bleeding, drain all fluid from the pleural space before the procedure, and leave a chest tube or catheter in place after pleurodesis until the patient meets predefined endpoints. (See 'Postprocedure chest tube management' below.)

Evaluate concomitant medications — We review a patient's medications before performing pleurodesis.

●Glucocorticoids – If possible, we reduce or hold glucocorticoids 24 to 48 hours prior to pleurodesis based upon the rationale that glucocorticoids may interfere with the inflammatory response necessary for successful pleurodesis [1-5].

●Nonsteroidal anti-inflammatory agents (NSAIDs) – We do not withhold NSAIDs prior to pleurodesis. Previously, concern existed that NSAIDs decreased the likelihood of successful pleurodesis [5], but studies suggest no negative effects [4,6].

●Other anti-inflammatories – We do not routinely discontinue other anti-inflammatory drugs or immunosuppressants before pleurodesis is performed, although the impact of such agents on pleurodesis effectiveness are unknown.

●Antiplatelet agents – For patients undergoing pleurodesis who are receiving antiplatelet therapy, the approach is individualized. Managing antiplatelet agents (eg, aspirin, clopidogrel, ticlopidine, ticagrelor, prasugrel) depends upon several factors including risk of arterial thrombosis (if drugs are temporarily held), risk of postintervention bleeding (if the drugs are continued), presence of an existing chest tube/catheter, urgency of need for pleurodesis, and planned approach (eg, thoracoscopy versus bedside catheter). A multidisciplinary team of cardiovascular physicians responsible for antiplatelet drug therapy and pleural interventionalists should discuss the relative risks and specific plans for management.

In the absence of high-quality studies, we adopt the following pragmatic approach.

•If a patient already has a chest tube in place, we proceed to pleurodesis because no studies report that intrapleural instillation of a sclerosant by itself increases bleeding risk for these patients.

•For patients who do not have a pre-existing chest tube and in whom pleurodesis can be delayed (eg, mild symptoms), we hold non-aspirin antiplatelet agents for three to seven days before chest tube insertion, provided it is anticipated that a sufficient course of antiplatelet therapy has been administered to allow temporary withholding. The optimal duration of temporary discontinuation depends upon the agent. In this population, we use small-bore catheters under image guidance to limit the bleeding risk.

•For patients with an urgent indication for pleurodesis (eg, significant symptoms) and in whom antiplatelet drugs cannot be held because of thrombotic risks, we perform pleurodesis via a small-bore catheter (eg, 12 to 14 French catheter) without delay. We avoid thoracoscopy in this situation since the bleeding risk is greater.

Limited data exist to guide management of antiplatelet therapy. Our experience and that of others suggest a low risk of serious bleeding (≤1.5 percent) for patients on antiplatelet agents with thoracentesis and/or small-bore thoracostomy tube placement [7-17]. No studies report the rate of bleeding after medical thoracoscopy for patients on antiplatelet agents. For pleural interventions, the risk of bleeding with aspirin appears similar to that of potent antiplatelet agents [8].

●Anticoagulants – For patients in whom a chest tube or catheter needs to be placed for chemical pleurodesis, we typically reverse or withhold systemic anticoagulation. However, this is not necessary if a chest tube is already in place. (See "Thoracostomy tubes and catheters: Placement techniques and complications", section on 'Patient preparation' and "Thoracostomy tubes and catheters: Placement techniques and complications".)

Pleural drainage for pleural apposition — For patients with a pleural effusion, we drain the pleural space as much as is feasible using the following:

•For patients with a chest tube or catheter in place, including a tunneled pleural catheter, we ensure that minimal evidence of fluid accumulation is present by chest radiograph or ultrasound. While some experts recommend delaying pleurodesis until daily chest tube drainage is less than 150 to 250 mL, two small studies report that this delay appears to be unnecessary [18-20]. Data to support pleurodesis via a tunneled catheter are provided separately. (See "Management of malignant pleural effusions", section on 'Talc pleurodesis plus an indwelling catheter'.)

•For those without a chest tube or catheter and in whom thoracoscopy is not planned, we drain the fluid typically using a small bore (12 to 14 French) catheter placed under imaging guidance and use that catheter for sclerosant delivery. The impact of tube size and duration of chest tube drainage are discussed separately. (See "Management of malignant pleural effusions", section on 'Chemical pleurodesis alone (bedside or thoracoscopic)'.)

•For those without a chest tube or catheter and in whom thoracoscopic pleurodesis is planned, pleural fluid is manually aspirated after the trocar or thoracoscope enter the pleural space. There is little risk for re-expansion edema because of pressure equilibrium in the pleural space during thoracoscopy. In addition, we also carefully lyse adhesions, if present, to maximize sclerosant distribution.

After pleurodesis, a chest tube or catheter is left in place to maintain a "dry" pleural space, the details of which are discussed below. (See 'Postprocedure chest tube management' below.)

CHOOSING A DELIVERY METHOD — Pleurodesis may be performed at the bedside (inpatient or outpatient) via a chest tube or catheter (including an indwelling pleural catheter) or performed thoracoscopically, either in an endoscopy suite (also known as medical thoracoscopy and pleuroscopy) or in an operating room (surgical or video-assisted thoracoscopy). Because of the absence of high-quality comparative clinical trial data, choosing among these is dependent upon factors including local expertise, patient preferences, condition requiring pleurodesis, comorbidities, and indications for a concurrent procedure. We engage in multidisciplinary conversations with the patient that involve a medical or interventional pulmonologist, thoracic surgeon, and/or interventional radiologist before proceeding with a specific method. For patients with malignant or nonmalignant pleural effusion, choosing a delivery method is discussed separately:

●(See "Management of malignant pleural effusions", section on 'Pleurodesis (alternative to IPC or failed IPC)'.)

●(See "Management of nonmalignant pleural effusions in adults", section on 'Pleurodesis type'.)

CHOOSING A SCLEROSING AGENT — Numerous chemical irritants have been successfully used to induce pleurodesis [21-29]. Agents include talc, tetracycline derivatives, bleomycin, silver nitrate, iodopovidone, mepacrine, and Corynebacterium parvum. The common mechanism of action between agents is that they all induce an intense inflammatory response resulting in deposition of fibrin and scar formation (ie, fibrosis) between the parietal and visceral pleura.

Available agents

Talc — The composition, formulations, and importance of particle size and delivery vehicle of talc are discussed below:

●Composition – Talc is predominantly hydrated magnesium silicate (Mg3Si4O10(OH)2) [30]. Talc may also contain several mineral contaminants (eg, magnesite, dolomite, kaolinite, calcite, chlorite, serpentine, and quartz); medicinal talc is asbestos-free [31]. Varying amounts of calcium, aluminum, iron, and lead may be present. According to the manufacturer's label, lead is present as an impurity in Steritalc; at the highest recommended dose of 10 grams of talc, up to 40 mcg of lead may be present [32], although no cases of lead toxicity have been described.

●Formulations and particle size – We use size-calibrated talc (ie, "graded" talc that contains less than 10 percent of small talc particles [eg, 5 to 10 microns in diameter]). Talc preparations with a high proportion of small particles are thought to be associated with more severe local and systemic inflammatory responses (eg, acute respiratory distress syndrome) [33,34] and with a poorer outcome [35]. (See 'Complications' below.)

•US formulations – "Graded" talc approved by the US Food and Drug Administration is provided in two forms:

-Sterile Talc Powder

-Talc aerosol canister that uses dichlorofluoromethane (CFC-12) as a propellant

In one study of commercially available talc in the US, sterile talc powder demonstrated a median talc particle diameter of 26.57 microns (range 0.399 to 100.237 microns); Sclerosol Intrapleural Aerosol had a median particle diameter of 24.49 microns (range 0.224 to 100.237 microns) [36]. Particle size increased when talc was exposed to a protein rich environment (>100 microns; ie, simulation for talc exposure in the pleural space). Talc in the US therefore seems to have size characteristics similar to previously described "graded" talc preparations. While approved, reduced supply of Sclerosol by the manufacturer has limited its use.

•European formulations – In Europe, commercial talc for pleurodesis is manufactured by Novatech and comes in four forms:

-Steritalc F2 (2 grams of sterile talc powder in a glass vial)

-Steritalc F4 (4 grams of sterile talc powder in a glass vial)

-Steritalc Spray (3 grams in a spray canister with propellant gas)

-Steritalc PF4 spray (4 grams in a hand/air-driven pump)

The French Novatech talc is size-calibrated with a median particle diameter of 31.3 microns. This talc preparation has removed most of the particles <10 microns [37].

Tetracycline derivatives — Minocycline and doxycycline have all been successfully used for pleurodesis (tetracycline is no longer available for clinical use).

Doxycycline and minocycline are administered as a solution [38-42]. Thus, they can be used for bedside as well as thoracoscopic procedures. Similar to talc, doxycycline and minocycline can be systemically absorbed, although adverse systemic reactions appear to be less common than with talc. (See 'Complications' below.)

Others — Other sclerosing agents, such as bleomycin, silver nitrate, iodopovidone, mepacrine, and Corynebacterium parvum are uncommonly used and their description for use is beyond the scope of this topic.

Investigational — Several agents are under investigation. In one retrospective study of an investigational agent, viscum, rates of successful pleurodesis were similar to those achieved with talc in patients with malignant pleural effusion (MPE) [43]. Further studies are needed before it can be used routinely as an alternative to talc or tetracycline-derivatives.

Our general approach — 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. While practice varies among clinicians and institutions, talc and tetracycline derivatives are the two most common agents used. We typically perform chemical pleurodesis using talc because of its high efficacy [44]. Tetracycline derivatives (typically doxycycline) are a reasonable alternative, although success rates may be lower than with talc.

Exceptions include the following:

•Patients undergoing bilateral pleurodesis – We avoid talc in these patients since the adverse effects of talc are thought to be dose-related and use of talc in these patients could potentially increase the risk of systemic inflammation and acute respiratory failure. These complications are discussed below. (See 'Complications' below.)

•Patients undergoing extensive pleural abrasion or multiple lung biopsies – We avoid talc in these patients since such interventions may increase the absorption of talc, and thereby, potentially increase the risk of systemic dissemination. (See 'Complications' below.)

•Patients who are pregnant – We avoid talc in pregnancy due to the theoretical risk of fetal exposure to small amounts of lead, which may exist as an impurity in some talc formulations [45]. However, the need for talc during pregnancy is rare and no case reports of lead toxicity have been described.

On the other hand, we avoid tetracycline derivatives in nursing females since tetracycline and its derivatives may be harmful to infants [46].

Data comparing agents are retrospective and mostly performed in patients with MPE. Choosing among the agents and efficacy data for select agents in patients with MPE and nonmalignant pleural effusion (NMPE) are described in separate topic reviews. (See "Management of malignant pleural effusions", section on 'Chemical pleurodesis alone (bedside or thoracoscopic)' and "Management of nonmalignant pleural effusions in adults", section on 'Pleurodesis type'.)

When talc is chosen, the clinician also needs to decide whether it should be administered as a powder (also known as talc poudrage) or as a slurry (powder mixed with saline). While clinician preference plays a role, traditionally, talc powder is used for patients undergoing thoracoscopy while talc slurry is used for patients undergoing pleurodesis at the bedside via a small-bore chest tube. In patients with MPE, talc powder appears equally effective as compared with talc slurry [47]. These data are discussed separately (see "Management of malignant pleural effusions", section on 'Chemical pleurodesis alone (bedside or thoracoscopic)'). Trials comparing talc slurry versus insufflation in refractory NMPE have not been reported.

PROCEDURE — In most institutions, pulmonologists and thoracic surgeons perform pleurodesis while in other institutions, interventional radiologists may also perform this procedure [48].

Sedation and analgesia — The chosen sedation and analgesia strategy depends upon whether the procedure is done via a chest tube or thoracoscopically. Importantly, chemical pleurodesis is painful due to a high concentration of pain receptors on the parietal pleura and requires attention be paid to pain control before, during, and after the procedure.

●Bedside pleurodesis – For bedside pleurodesis, we typically use conscious sedation with an anxiolytic/amnestic agent (eg, midazolam). The patient is spontaneously breathing throughout the procedure. Further details on conscious sedation are provided separately (See "Procedural sedation in adults in the emergency department: General considerations, preparation, monitoring, and mitigating complications".)

We pretreat patients with parenteral doses of an opiate (eg, morphine 1 mg intravenously) or a nonsteroidal anti-inflammatory agent (NSAID). Additionally, the British Thoracic Society guidelines for managing malignant pleural effusions recommend that lidocaine (3 mg/kg; maximum 250 mg) be instilled intrapleurally via the chest tube or catheter just before administration of the sclerosant [49]. After instillation of the anesthetic, the chest catheter is flushed with saline before instilling the sclerosant; when talc is used, this step avoids adsorption of the anesthetic onto the talc.

●Thoracoscopic pleurodesis – Sedation and analgesia for thoracoscopic pleurodesis is similar to thoracoscopy for other procedures.

Specific for pleurodesis, some experts provide additional topical anesthesia (via a second cannula/trocar or through the working channel of the scope) to the pleura when planning pleurodesis (eg, 1 or 2 percent lidocaine via spray catheter; 3 mg per kg; maximum 250 mg) just prior to sclerosant administration. Further details regarding medical thoracoscopy are provided separately. (See "Medical thoracoscopy (pleuroscopy): Equipment, procedure, and complications", section on 'Anesthesia' and "Anesthesia for video-assisted thoracoscopic surgery (VATS) for pulmonary resection".)

For patients undergoing additional video-assisted thoracoscopic surgery (VATS) for additional intrathoracic procedures (eg, biopsy, blebectomy), general anesthesia and mechanical ventilation (using a single- or double-lumen endotracheal tube) is typical. Lidocaine is not instilled into the pleural space during VATS. Further details regarding VATS are provided separately (See "Anesthesia for video-assisted thoracoscopic surgery (VATS) for pulmonary resection".)

Agent preparation and instillation — After ensuring adequate sedation and analgesia, drainage or fluid or air, and access to the pleural space, the sclerosing agent is prepared and administered. Preparation and administration of common agents is as follows:

●Talc – Preparation depends upon whether talc is administered as a slurry (for bedside catheter administration) or as a dry powder (via thoracoscopy).

•Talc slurry – Talc slurry is a nondissolving suspension of talc powder in saline. A volume of 50 mL of 0.9 percent sterile saline is injected into the talc powder bottle (usually 5 grams) using a 16-gauge needle attached to a 60 mL LuerLock syringe. The bottle should be swirled continuously. The slurry suspension is then aspirated back into the 60 mL syringe or divided (25 mL each) into two 60 mL syringes that are each additionally diluted with 25 mL of sterile saline. The syringe(s) containing the talc slurry should be continuously agitated to suspend the talc. The slurry should be injected within 12 hours of preparation.

After sterilizing the site of injection, the slurry is injected intrapleurally either via an injection into the chest tube proximal to a section of tube that is clamped with a rubber-tipped Kelly clamp or via a port of a three-way stopcock. Generally, 3 to 5 grams of talc is administered into the pleural space. Following administration, the chest tube is left in place and either clamped or left to water seal.

We do not rotate the patient after the slurry has been administered. While talc slurry distributes quite poorly over the pleural surfaces and tends to collect at the caudal sinuses [50], rotation of the patient with the purpose to spread the slurry more evenly has not been shown to increase the likelihood of successful pleurodesis [22].

•Talc poudrage (via thoracoscopy) – Dry talc powder is available in pressurized canisters that do not require preparation (usually 4 grams). The canister has a device that can attach to a pleural trocar that has been inserted into the chest as part of the thoracoscopic procedure (also known as talc insufflation). Similar to talc slurry, approximately 3 to 4 grams of talc are insufflated by pressing the button on the canister. The distal end of the delivery tube should be pointed in several different directions while short bursts are administered to distribute the talc powder equally and extensively on the visceral and parietal pleural surfaces. Sudden decompression of the propellant gasses can cause pain in conscious patients because of sudden drops in temperature.

Alternatively, talc can be insufflated (usually under direct vision) by hand-driven air pumping of talc powder from a glass or plastic vial via the trocar.

After insufflation, the trocars are removed, and a chest tube is placed.

“Rapid” pleurodesis that combines talc pleurodesis with a tunneled catheter is described in patients with malignancy. (See "Management of malignant pleural effusions", section on 'Talc pleurodesis plus an indwelling catheter'.)

●Tetracycline derivatives – The typical dose of doxycycline used for intrapleural instillation is 500 mg dissolved in a total volume of 50 mL of sterile 0.9 percent saline [40,41]. It is delivered in a similar fashion to talc slurry. The recommended dose for minocycline is 150 to 300 mg in 50 to 100 mL of sterile 0.9 percent saline [51]. After sclerosant delivery, the chest tube or catheter is clamped. Studies with tetracycline derivatives also show no need to rotate the patient [52,53].

Follow-up — After agent administration, the chest tube is either clamped or left to water seal with a loop over an intravenous pole; both of these maneuvers ensure that the talc remains in the pleural space while allowing complete re-expansion of the lung and good apposition of pleural surfaces. After one to two hours, the chest tube is allowed to drain to gravity, although some experts place the chest tube on suction. We ensure that the patient's pain is adequately controlled and observe the patient for success or failure of the procedure.

Postprocedure analgesia — We provide postprocedure analgesia to maintain comfort. We typically use scheduled and breakthrough doses of an NSAID and/or opiate with a plan to wean off opiates in a short period of time (eg, one to two days). Over one-quarter of patients require rescue opioid therapy regardless of initial standing analgesia administered (higher if on NSAIDs) [6]. Pain typically improves dramatically after the chest tube is removed, but some patients have prolonged pain and rarely, some develop postthoracotomy syndrome. The management of postpleurodesis pain is discussed separately. (See "Pneumothorax: Definitive management and prevention of recurrence", section on 'Postpleurodesis pain' and "Approach to the management of acute pain in adults", section on 'Strategy based on expected degree and duration of pain'.)

Postprocedure chest tube management — The duration of chest tube drainage varies. While some clinicians leave the chest tube or catheter in place until fluid drainage is less than 150 to 250 mL per day, others remove it at 24 hours based upon limited data that suggest that success rates are similar between the two approaches. These data are discussed separately. (See "Management of malignant pleural effusions", section on 'Chemical pleurodesis alone (bedside or thoracoscopic)'.)

Assessing success or failure — Once the chest tube is removed, we typically follow patients clinically and radiographically, the frequency of which, depends upon the patients' symptoms. For most patients, a chest radiograph is sufficient, although patients with loculated pleural effusion may need computed chest tomography to examine the pleural space in sufficient detail. Success means limited or no recurrence of pleural fluid (even if loculated), no symptoms, and no indication for another procedure.

Chemical pleurodesis is reported to have a success rate of up to 90 percent but depends on the agent used, the underlying condition, medications, and the presence of fluid in the pleural space at the time of the procedure. Further details regarding success associated with agents used are provided separately. (See 'Our general approach' above and "Management of malignant pleural effusions", section on 'Chemical pleurodesis alone (bedside or thoracoscopic)' and "Management of nonmalignant pleural effusions in adults", section on 'Pleurodesis type'.)

Some patients fail chemical pleurodesis. Options for refractory pleural effusion or pneumothorax are discussed separately. (See "Management of malignant pleural effusions", section on 'Refractory malignant pleural effusion' and "Management of nonmalignant pleural effusions in adults", section on 'Refractory effusions'.)

COMPLICATIONS — Chemical pleurodesis is a safe procedure. Most of the complications of pleurodesis appear to be related to the sclerosing process and are likely to occur with all sclerosants, although some complications appear to be sclerosant- and dose-specific. In this section, we are discussing complications related to chemical agent and not to the method of delivery.

●Common complications (pain, fever) – The most common adverse sequelae of chemical pleurodesis are fever (up to 35 percent) and pain [33,54]. Management of postoperative pain is discussed above. (See 'Postprocedure analgesia' above.)

●Less common complications – Less commonly, patients may experience systemic inflammation and respiratory failure, cardiovascular complications, empyema, and decreased lung volume. Mortality does not appear to be increased compared with tube or catheter drainage alone [54].

•Systemic inflammation and acute respiratory failure – A mild systemic inflammatory reaction is common following chemical pleurodesis [37]. As an example, in a retrospective study of 35 patients, those who received talc insufflation via thoracoscopy had an increased temperature, white blood cell count, and C-reactive protein level compared with patients that underwent thoracoscopy alone [55].

Severe systemic inflammation with hypotension and acute respiratory failure due to acute respiratory distress syndrome (ARDS) is rare. In our experience, systemic inflammation and ARDS are more commonly seen after talc pleurodesis compared with other sclerosant agents [56,57]. Systemic inflammation after talc pleurodesis appears to be linked to the systemic absorption of talc particles. Systemic absorption is increased when talc particles are small (eg, ungraded talc), when a large total dose of talc is used (eg, bilateral pleurodesis), and when an access route that facilitates systemic absorption is created (eg, pleural abrasion or multiple parietal pleura biopsies) [58]. It is unlikely that the method of administration (insufflation versus slurry) plays a major role in the development of systemic inflammation and respiratory failure. Particle size is discussed separately. (See 'Talc' above.)

This phenomenon may be less likely to occur now that "graded" talc is used (ie, size-calibrated talc with average particle size >10 microns). One case series of pleurodesis using graded-size talc noted no instances of respiratory failure in 558 patients [59]. However, higher than usual amounts of talc may increase the risk even when graded talc is used. In a retrospective cohort study of 138 patients undergoing thoracoscopic talc insufflation, among those treated with >5 g of talc, acute lung injury occurred in 2.8 to 5.6 percent of patients, although no patient developed ARDS [60].

At least one case of acute hypoxic/hypercapnic respiratory failure has been reported after pleurodesis with doxycycline (300 mg), but whether this was due to concomitant lidocaine is unclear [61]. Chest radiograph showed no pulmonary opacities and the presence of high peak ventilator pressures suggested acute bronchospasm due to an anaphylactic reaction. The patient improved in a few hours with ventilatory support and bronchodilator therapy.

•Cardiovascular complications – Cardiovascular complications, such as arrhythmias, cardiac arrest, chest pain, myocardial infarction, and hypotension, have been reported following pleurodesis [37]. However, it is unclear whether these complications are a result of the surgical procedure, comorbid conditions, or the chemical sclerosant.

•Empyema – Bacterial empyema has been reported following pleurodesis using talc slurry (0 to 11 percent), talc insufflation (0 to 3 percent), and rarely tetracycline [62,63]. Local site infection is uncommon.

•Reduced lung volume – Pleurodesis restricts lung expansion. Thus, some patients may show evidence of lung restriction on pulmonary function testing, although the degree of restrictive impact is likely minimal. (See "Overview of pulmonary function testing in adults", section on 'Restrictive ventilatory defect'.)

•Acute kidney injury – Acute kidney injury has been anecdotally noted.

A link between talc and cancer has been reported in individuals who mine and process talc [64]. This association has been attributed to asbestos within the talc. As a result, there is a theoretical concern that talc pleurodesis could place the patient at increased risk for mesothelioma or lung cancer [65]. However, the incidence of malignancy is not increased in patients who undergo talc pleurodesis and talc used for medical purposes is asbestos-free [66,67].

There is a misconception that pleurodesis reduces the ability of patients to have subsequent surgery, such as lung transplantation. Contrary to this belief, patients who have undergone pleurodesis can receive lung allografts or undergo thoracic surgery. However subsequent thoracic surgery after pleurodesis is technically more complicated, takes longer, and increases the risk of bleeding. (See "Lung transplantation: Procedure and postoperative management".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pleural effusion".)

SUMMARY AND RECOMMENDATIONS

●Clinical applications and contraindications – Malignant pleural effusion (MPE) is the most common and widely accepted indication for chemical pleurodesis. Chemical pleurodesis is also sometimes used to manage refractory nonmalignant pleural effusions (NMPE). Contraindications to pleurodesis are similar to those for thoracentesis (eg, severe and uncorrectable bleeding diathesis, infection at the chest tube or thoracoscopic insertion site) with the added contraindications of nonexpandable lung and untreated intrapleural infections (See 'Clinical applications' above.)

●Preprocedure preparation – We perform the following:

•For patients in whom chemical pleurodesis is planned, we reduce or temporarily discontinue systemic glucocorticoid therapy, if feasible. Glucocorticoids are held or reduced for 24 to 48 hours prior to the procedure to optimize the inflammatory effects of the sclerosant. We do not withhold nonsteroidal anti-inflammatory agents (NSAIDs) prior to pleurodesis since data suggest no adverse effects. Anticoagulants are typically held or reversed. The approach to holding antiplatelet agents is individualized.

•Additional preparation involves ensuring that as much fluid as is possible be drained from the pleural space with a chest tube or catheter, unless a thoracoscopic pleurodesis is planned. (See 'Preprocedure preparation' above.)

●Sclerosant – For most patients, we suggest talc rather than other sclerosants (Grade 2C). Tetracycline derivatives (typically doxycycline) are a reasonable alternative, although success rates may be lower than with talc; important exceptions to the use of talc include patients undergoing bilateral pleurodesis, patients undergoing extensive pleural abrasion or multiple lung biopsies, and pregnant females. Choosing among the agents and efficacy data for select agents in patients with MPE and NMPE are described in separate topic reviews. (See 'Choosing a sclerosing agent' above and "Management of malignant pleural effusions", section on 'Chemical pleurodesis alone (bedside or thoracoscopic)' and "Management of nonmalignant pleural effusions in adults", section on 'Pleurodesis type'.)

●Procedure

•Chemical sclerosant is instilled through a chest tube or catheter at the bedside or via a trocar at thoracoscopy. (See 'Choosing a delivery method' above.)

•For bedside pleurodesis, we typically use conscious sedation with an anxiolytic/amnestic agent (eg, midazolam). We also instill lidocaine (3 mg/kg; maximum 250 mg) intrapleurally via the chest tube or catheter just before administration of the sclerosant for local pain control. Further details on conscious sedation are provided separately (See "Procedural sedation in adults in the emergency department: General considerations, preparation, monitoring, and mitigating complications".)

•Sedation and analgesia for thoracoscopic pleurodesis is similar to thoracoscopy for other procedures. Some experts also administer lidocaine spray prior to sclerosant administration (similar to that described for bedside pleurodesis above). Medical thoracoscopy is described in detail separately. (See "Medical thoracoscopy (pleuroscopy): Equipment, procedure, and complications", section on 'Anesthesia' and "Anesthesia for video-assisted thoracoscopic surgery (VATS) for pulmonary resection".)

•The sclerosant is administered and the chest tube or catheter clamped for one to two hours, then unclamped. (See 'Agent preparation and instillation' above.)

•The duration of chest tube drainage varies. While some clinicians leave the chest tube or catheter in place until fluid drainage is less than 150 to 250 mL per day, others remove it at 24 hours based upon limited data that suggest that success rates are similar between the two approaches. (See 'Postprocedure chest tube management' above.)

•Scheduled and break through doses of an NSAID and/or opiate are administered for pain with a plan to wean them once the chest tube or catheter is removed and recovery ongoing. (See 'Postprocedure analgesia' above.)

●The most common short-term adverse effects of chemical pleurodesis include fever and pain. Uncommon adverse effects include systemic inflammation, acute respiratory failure, cardiovascular complications, empyema, and reduced lung volumes. (See 'Complications' above.)