INTRODUCTION — Pleurodesis is a procedure performed to obliterate the pleural space to prevent recurrent pleural effusion or pneumothorax or to a treat persistent pneumothorax. Pleurodesis is commonly accomplished by draining the pleural fluid, when present, followed by either a mechanical procedure (ie, abrasion, or (partial) pleurectomy) or instillation of a chemical irritant into the pleural space, which causes inflammation and fibrosis. Talc pleurodesis is a specific form of chemical pleurodesis. Talc is the most effective sclerosant available for pleurodesis in malignant pleural effusion [1]. As compared to indwelling pleural catheter placement, talc pleurodesis has been shown to be equally effective in relieving dyspnea [2].
This topic will review the indications, contraindications, patient selection, procedure, and outcomes of talc pleurodesis. Discussions of the management of malignant and refractory nonmalignant pleural effusions and an overview of chemical pleurodesis are provided separately. (See "Management of malignant pleural effusions" and "Management of nonmalignant pleural effusions in adults" and "Chemical pleurodesis".)
WHAT IS TALC — Talc is predominantly hydrated magnesium silicate (Mg3Si4O10(OH)2), and was first used for pleurodesis in 1935 [3]. Varying amounts of calcium, aluminum, iron, and lead may be present, according to the origin of the formulation. Talc may also contain several mineral contaminants (eg, magnesite, dolomite, kaolinite, calcite, chlorite, serpentine, and quartz); medicinal talc is asbestos-free [4]. 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 [5].
Particle size — Talc preparations with a high proportion of particles <5 to 10 micron in diameter are associated with more severe local and systemic inflammatory responses [6,7] and with a poorer outcome [8]. However, formal standards for talc production for pleurodesis are lacking, and there is a wide variation in composition and particle size in the various talc preparations used worldwide [9].
●In the USA, talc pleurodesis approved by the Food and Drug Administration is provided in two forms: sterile talc powder and as a talc aerosol canister with two delivery tubes (4 grams of talc per tube) that use dichlorofluoromethane (CFC-12) as a propellant. The particle size distribution for the FDA-approved talc has not been disclosed by the manufacturer. A similar mixed talc has been reported to have a mean particle size of approximately15 microns [10]. Sterile talc powder (4 grams of graded talc by Novatech), or Sclerosol Intrapleural Aerosol (by Bryan) have been approved in the United States, with the same specifications as in Europe (see bullet below). In one study, sterile talc powder demonstrated a median talc particle diameter of 26.57 microns with a range of particle sizes from 0.399 microns to 100.237 microns [11]. Sclerosol demonstrated a median diameter of 24.49 microns with a range of particle sizes from 0.224 microns to 100.237 microns. The exposure of talc to a protein rich environment (bovine serum albumin and human pleural fluid) led to the development of measurable, new, larger aggregated particle (>100 microns). United States talc 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.
●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), and 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 been reported to have most of the particles <10 microns removed [10].
Mechanism of action — Talc instillation (by insufflation or slurry) causes an intense intrapleural inflammatory response characterized by the production of cytokines, adhesion molecules, and other mediators of inflammation, such as interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-beta) [9]. Among other effects, IL-8 induces neutrophil influx involved in the acute inflammatory response; VEGF causes increased capillary permeability and angio- and lymphogenesis; and TGF-beta contributes profibrotic and immunomodulatory properties. It is important to note that provoking pleural inflammation using talc, however intense, will be inadequate if the visceral and parietal pleura are physically separated. Keeping the pleural cavity dry after pleurodesis (hence, adequate drain insertion technique and control of pleural drainage) are important success factors [12]. (See 'Patient preparation' below.)
PATIENT SELECTION
Indications and efficacy — Talc pleurodesis is used to manage recurrent malignant pleural effusions, refractory symptomatic non-malignant pleural effusions, and recurrent and persistent primary and secondary spontaneous pneumothoraces.
Talc pleurodesis is generally associated with a 90 percent success rate or greater. However, rates vary depending upon the indication and length of follow up. As an example, a case series of 611 patients who underwent video-assisted thoracoscopic surgery (VATS)-directed talc pleurodesis for a pleural effusion reported a success rate of only 69 percent, defined as a fully expanded lung at the end of the procedure and no recurrence of the effusion at long-term follow up [13]. Risk factors for unsuccessful pleurodesis included previous thoracic irradiation and a chest tube duration >10 days, while risk factors for death included a Karnofsky index <50 percent, a body mass index <25 kg/m2, malignancy, and male sex. Several reasons were proposed for the low success rate compared to prior reports, including the large number of unselected cases, the strict definition of successful pleurodesis, and the large number of patients who had a Karnofsky Index ≤60 percent (a risk factor for unsuccessful pleurodesis).
Recurrent malignant effusion — Chemical pleurodesis by catheter or thoracoscopy is recommended for most patients whose malignant pleural effusion reaccumulates sufficiently rapidly to make multiple repeat thoracenteses burdensome. (See "Management of malignant pleural effusions".)
Refractory non-malignant effusion — Talc pleurodesis is sometimes used to treat refractory symptomatic non-malignant effusions, including those caused by chronic ambulatory peritoneal dialysis, yellow nail syndrome, chylothorax, nephrotic syndrome, lupus, hepatic hydrothorax, and heart failure. (See "Management of nonmalignant pleural effusions in adults".)
A controversial aspect of using talc pleurodesis for the treatment of refractory non-malignant pleural effusions is concern about exposure of patients with non-malignant disease to rare, but potentially severe adverse effects associated with talc pleurodesis [14,15]. (See 'Complications and safety' below.)
Recurrent and persistent spontaneous pneumothorax — Primary spontaneous pneumothorax and secondary spontaneous pneumothorax both occur in the absence of a precipitating event. However, the former occurs in the absence of lung disease, while the latter occurs in the presence of lung disease, although the presence of underlying lung disease is not always readily evident. Pleurodesis is indicated for prevention after a recurrent primary spontaneous pneumothorax or a first secondary spontaneous pneumothorax [13,16-19]. The choice of chemical or mechanical pleurodesis in these settings is described separately. (See "Pneumothorax in adults: Epidemiology and etiology" and "Treatment of secondary spontaneous pneumothorax in adults".)
Contraindications — Successful pleurodesis requires physical contact between the visceral and parietal pleura. In cases of incomplete expansion of the lung (eg, lung entrapment or insufficient drainage), pleurodesis with talc (or any other agent) will fail. In patients with severe underlying lung disease, the benefit of non-size-calibrated talc should be weighed against the small risk of deterioration in pulmonary function with severe post talc inflammation. (See 'Complications and safety' below.)
The manufacturer of the French-graded talc (Steritalc) counsels against the use of talc in pregnant women (and children) due to the small amount of lead content that is present in talc as an impurity [5]. While no case reports of lead toxicity have been described, it is prudent to avoid talc in pregnant women due to the increased sensitivity of infants and children to lead exposure.
Patient selection and outcome predictors — Certain patient (eg, cigarette smoking) and pleural fluid characteristics (eg, malignancy) are associated with greater and lesser degrees of success with talc pleurodesis. These features are discussed separately. None of these findings, however, has sufficient predictive power to exclude patients from a talc pleurodesis attempt [20-22]. (See "Management of malignant pleural effusions" and "Management of nonmalignant pleural effusions in adults".)
Although talc pleurodesis remains the most successful procedure, evidence suggests that indwelling pleural catheter placement (preferably with concurrent installation of talc slurry) in those with malignant effusions may be appropriate in individual cases because of shorter times spent in hospital, fewer admissions, fewer re-interventions, and superior cost-effectiveness [23-28].”
PATIENT PREPARATION — Success of chemical pleurodesis is largely dependent on achieving apposition of the visceral and parietal pleural surfaces. To achieve proper apposition, the pleural space needs to be emptied of air or pleural fluid either by chest tube drainage prior to the procedure or at the time of thoracoscopy. Pleural drainage by tube thoracostomy in preparation for pleurodesis is discussed in greater detail separately. (See "Chemical pleurodesis" and "Thoracostomy tubes and catheters: Indications and tube selection in adults and children".)
Concomitant medications — Systemic glucocorticoid therapy may decrease the success of pleurodesis due to its potent antiinflammatory effects [29,30]. This is supported by studies in humans that have shown decreased success of talc pleurodesis in association with glucocorticoid use [31]. Thus, whenever possible, glucocorticoids should be tapered or discontinued several days prior to pleurodesis.
Data regarding the use of nonsteroidal anti-inflammatory agents are conflicting; in animal models, diclofenac was shown to decrease the effectiveness of talc pleurodesis [30], whereas ketoprofen did not [32]. However, in humans, another study reported noninferiority when NSAIDS were compared with opioids [33]. Thus, NSAIDS do not necessarily need to be avoided in those undergoing talc pleurodesis.
Systemic anticoagulation is generally reversed for video-assisted thoracoscopy and for placement of a chest tube. It is not necessary to hold anticoagulation for instillation of talc slurry once the chest tube is in place.
TALC INSUFFLATION OR TALC SLURRY? — The choice between talc insufflation (thoracoscopic) or talc slurry (via chest tube) usually depends more on the medical circumstances requiring pleurodesis than the relative efficacy of the two procedures. When pleural malignancy is identified during a diagnostic thoracoscopy, it is reasonable to proceed with talc insufflation during the procedure. In patients with a low Karnofsky index (table 1), talc slurry is often preferred because it is less invasive.
Talc insufflation is at least equally effective and, in some studies, including a randomized trial, significantly more effective than talc slurry; slurry has never been shown to be superior to insufflation [34-41]. In a randomized trial that assigned 482 patients with malignant pleural effusions to receive talc insufflation or slurry, there was a trend toward greater success at 30 days among the patients who received talc insufflation (78 versus 71 percent) [38]. In the subgroup of patients with primary lung or breast cancer, talc insufflation was significantly more successful at 30 days (82 versus 67 percent). Respiratory failure developed in 19 patients (8 percent) who received talc insufflation and 10 patients (4 percent) who received talc slurry. Both groups had a mortality of approximately 2 percent [38].
Trials comparing talc slurry versus insufflation in refractory nonmalignant effusion and spontaneous pneumothorax have not been reported; however, it seems likely that results would be similar.
Patient and clinician preferences also have a role in deciding between insufflation and slurry. The principal issues include duration of procedure, degree of invasiveness, and discomfort.
PLEURODESIS PROCEDURE — Talc is delivered to the pleural space for pleurodesis via one of two procedures: thoracoscopy for talc insufflation and tube thoracostomy for talc slurry. The choice between these procedures is discussed above. (See 'Talc insufflation or talc slurry?' above.)
Talc insufflation — Talc insufflation (also called thoracoscopic talc poudrage) is only performed during a thoracoscopic procedure.
Sedation and analgesia — Adequate sedation and analgesia must be assured. One of three types of sedation may be used:
●Local analgesia, conscious sedation, and spontaneous ventilation
●Total intravenous anesthesia with spontaneous breathing
●Total intravenous anesthesia and mechanical ventilation (using a single or double lumen endotracheal tube). (See "Medical thoracoscopy (pleuroscopy): Equipment, procedure, and complications".)
In patients with a spontaneous pneumothorax and thus normal pleural surfaces, talc insufflation can be particularly painful; intravenous injection of an opiate and intrapleural administration of 25 mL (250 mg) of 1 percent lidocaine via spray is administered by most experts to control pain [42].
In cases of pleurodesis for benign or malignant pleural disease and thus abnormal pleural surfaces, talc insufflation is typically less painful than when performed for pneumothorax.
Insufflation — After aspiration of all pleural fluid (there is thought to be little risk for reexpansion edema because of pressure equilibrium in the pleural space), and careful lysis of adhesions when indicated (in order to maximize the pleural surfaces that can be reached), 3 to 5 grams of talc are insufflated into the pleural space. For pneumothorax pleurodesis, 3 grams of talc are sufficient.
Talc powder can be administered (usually without visualization) from pressurized canisters via a delivery tube with one end attached to the canister and the other end inserted through a pleural trocar into the pleural space. The aerosol is administered 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, in order 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.
After talc insufflation, a chest tube (16 to 24 Fr) is left in place, and negative pressure is applied (5 to 20 cm H2O). We typically remove the chest tube after 24 hours, although traditional practice has been to remove the chest tube when pleural fluid drainage is less than 150 mL per day. Data from talc slurry pleurodesis suggest that the tube can be removed within 24 hours after talc injection, regardless of daily fluid production [43,44]. (See 'Talc slurry' below.)
Talc slurry — Administration of talc slurry via a chest tube is performed after complete drainage of the pleural space (ie, when complete lung expansion is documented).
Slurry preparation — Talc slurry is a nondissolving suspension of talc powder in saline, and must be prepared. A volume of 50 mL of sodium chloride 0.9 percent should be injected into the talc powder bottle using a 16-gauge needle attached to a 60 mL LuerLock syringe. The bottle should be swirled continuously. The contents of the bottle can then be aspirated back into a 60 mL syringe, or divided (25 mL each) in two 60 mL syringes, and additionally diluted with 25 mL of sodium chloride in each syringe. The slurry should be injected within 12 hours of preparation.
Sedation and analgesia — Once full expansion of the lung has been documented with a radiograph and the talc slurry prepared, administer an intravenous analgesic (eg, morphine, piritramide) and an anxiolytic/amnestic (eg, midazolam). Additionally, most clinicians spray 25 mL (250 mg) of 1 percent lidocaine intrapleurally a few minutes before talc slurry administration [42]. Lidocaine is not given together with the talc to avoid its adsorption onto the talc.
Slurry instillation — The syringe(s) containing the talc slurry should be continuously agitated to suspend the talc. After sterilizing the site of injection, the slurry (usually 5 grams) is injected intrapleurally either via an injection into the chest tube proximal to a clamped section of tube or via a port of a three-way stopcock. Talc slurry distributes quite poorly over the pleural surfaces, and tends to collect at the caudal sinuses [35]. Rotation of the patient, however, with the purpose to spread the slurry more evenly has not been shown to increase the likelihood of successful pleurodesis [45].
The chest tube should stay clamped for one hour; thereafter active suction (5 to 20 cm H2O) is warranted. We typically remove the chest tube after 24 hours, although traditional practice has been to remove the chest tube when pleural fluid drainage is less than 150 mL per day. The rationale was that leaving the chest tube in position maintained apposition of the pleural surfaces and pleurodesis could be repeated if pleural fluid drainage did not decrease. However, there is no empiric evidence that this strategy is superior to removing the tube within 24 hours regardless of the amount of fluid drainage. In a trial that randomly assigned 41 patients with a malignant pleural effusion to have their chest tube removed either 24 hours or 72 hours after talc pleurodesis, there was no difference in the success rate [44]. (See "Chemical pleurodesis", section on 'Technique'.)
COMPLICATIONS AND SAFETY — Talc pleurodesis with modern, purified, graded talc preparation is safe and highly effective. Talc is an inexpensive and accessible option that remains appropriate for pleurodesis despite some existing controversies [46].
The most common adverse events occurring after talc pleurodesis are fever (10 to 17 percent), pain, and gastrointestinal symptoms [41,47,48]. Less common side effects include arrhythmia, dyspnea, respiratory failure, systemic inflammatory responses, empyema, and talc dissemination.
●In patients with malignant pleural effusions, talc pleurodesis does not increase mortality compared with chest tube drainage alone or chemical pleurodesis with other agents [41].
●When used to treat nonmalignant effusions, talc slurry is associated with mild complications [49,50]. As an example, in a study that used talc slurry for nonmalignant effusions in 22 patients, all patients had mild pain, four had a low grade fever, and one patient developed an empyema [50].
●Complications among patients administered talc insufflation for pneumothorax were also mild. For example, among 41 patients who had talc insufflation for secondary pneumothorax due to COPD, the following symptoms were noted: pain in 13, fever in 5, subcutaneous emphysema in 27, and prolonged air leak in 7 [51]. Postoperative chest tube drainage and hospital stay were 4 and 5 days, respectively.
Despite small components of lead in Steritalc, no case reports of lead toxicity have been described.
In addition to side effects related to talc, other complications may arise related to chest tube placement and thoracoscopy. These are discussed separately. (See "Medical thoracoscopy (pleuroscopy): Equipment, procedure, and complications", section on 'Complications' and "Thoracostomy tubes and catheters: Placement techniques and complications", section on 'Morbidity and mortality'.)
Insufflation versus slurry — One question is whether patients experience any difference in side effects with talc given by insufflation compared to slurry. A few trials have reported the relative risk of complications with insufflation versus slurry for recurrent malignant effusions [36-38]. As an example, a randomized trial of 482 patients reported treatment-related deaths after insufflation (9 patients) and slurry (7 patients), a difference that was not statistically significant [38]. Because non-size-calibrated talc was used in this study, the risk of these severe side effects may be higher than would be seen with size-calibrated talc.
In the same study, chest pain (5 to 10 percent), fever (30 to 35 percent), and dyspnea (16 percent) were common, but not significantly different between the groups [38]. A trend towards an increase in deep venous thrombosis, red cell transfusions, and pneumonia was noted in the insufflation group. Other smaller trials have not found differences in duration of chest tube drainage, hospital stay, parenteral narcotic requirements, chest pain, or fever [36,37].
Systemic inflammation and respiratory failure — Systemic inflammation and acute respiratory failure has been reported after the instillation of talc [52,53]. 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, when a large total dose of talc is used, and when an access route that facilitates systemic absorption (eg, pleural abrasion or multiple parietal pleura biopsies) is created [9]. "Small particle size talc" (greater than 10 to 50 percent of particles smaller than 5 to 10 microns) has been shown in experimental animal studies to be systemically absorbed, and in a human study to cause a more intense pleural, lung, and systemic inflammation characterized by fever and increased serum C reactive protein levels, without increasing the likelihood of successful pleurodesis [4,6,9,10,54]. The extent, degree and type of intrapleural inflammation may also contribute to this "leaking" of talc particles into the systemic circulation.
The likelihood of talc-induced lung injury may be related to the talc size (or grade) and the amount of talc, rather than the patient’s preoperative respiratory reserve [38,48,55,56]. This notion is supported by two observational studies. The first was a multicenter prospective cohort study of 558 patients who underwent talc poudrage for malignant pleural effusion [57]. There were no reported instances of acute lung injury or acute respiratory distress syndrome (ARDS) during the study. The talc used was large grade and the amount was limited to four grams. The second was a single center retrospective cohort study of 138 patients undergoing thorascopic talc insufflation [58]. In this study, some patients received a higher dose of talc (median talc dose was six grams) than in the previous study. Acute lung injury occurred in 2.8 to 5.6 percent of patients, although nobody developed ARDS.
However, when non-size-calibrated talc is used, a dose of less than 5 grams of talc is not entirely without risk. Among 138 patients who underwent thoracoscopic talc insufflation using non-size-calibrated sterile talc (Sclerosol, available in the United States), talc-related lung injury developed in four, and, in two of them, the dose of talc was less than 5 grams [58]. Talc may have contributed to respiratory deterioration in an additional four patients, one of whom received less than 5 grams of talc.
Method of administration may affect the rate. As an example, respiratory failure has been reported to occur in four percent of talc slurry patients and eight percent of the talc insufflation patients [38].
Based upon these studies talc should be of a pharmaceutical grade and less than five grams should usually be insufflated into the pleural space.
Long-term adverse effects — Long-term adverse effects related to talc pleurodesis appear minimal [6,59,60]. Specifically, in patients administered talc for pneumothorax, no significant impairment in lung function, development of fibrosis, or increased likelihood of cancer has been documented. In addition, talc pleurodesis does not preclude subsequent ipsilateral lung surgery [19,60].
Measures to improve safety — Measures to improve the safety of talc pleurodesis include the following [6,57]:
●Use size-calibrated talc with less than 10 percent small particles (eg, 5 to 10 microns)
●Use no more than 5 grams of talc
●Avoid simultaneous bilateral pleurodesis to minimize the total dose of talc
●Avoid talc administration following extensive pleural abrasion or multiple biopsies
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
●Talc (hydrated magnesium silicate) is an effective choice for chemical pleurodesis. It may be administered by insufflation at the time of thoracoscopy or by slurry through a chest tube. (See 'Introduction' above.)
●Talc pleurodesis may be used to manage a recurrent malignant pleural effusion, a refractory symptomatic non-malignant pleural effusion, and also a recurrent primary spontaneous pneumothorax and secondary spontaneous pneumothorax. (See 'Indications and efficacy' above.)
●Talc insufflation and slurry appear to be equally effective for achieving pleurodesis. (See 'Talc insufflation or talc slurry?' above.)
●For patients with malignant effusion who are undergoing thoracoscopy for diagnosis, we suggest talc insufflation at the time of the procedure rather than subsequent talc slurry (Grade 2B). For patients with recurrent malignant pleural effusion who are too ill or prefer not to undergo thoracoscopy, pleural drainage by chest tube followed by talc slurry is a reasonable alternative. (See 'Talc insufflation or talc slurry?' above.)
●We suggest that glucocorticoid and NSAID therapy be reduced or discontinued prior to chemical pleurodesis, whenever possible (Grade 2C). (See 'Patient preparation' above.)
●For patients undergoing talc pleurodesis, we recommend NOT using more than 5 grams of talc, NOT performing bilateral pleurodesis, and NOT performing pleurodesis after pleural abrasion (Grade 1C). A size-calibrated formulation of talc that contains LESS than 10 percent of small particles (5 to 10 microns) is preferred, when available, because centers using these formulations have rarely observed respiratory failure following talc pleurodesis. (See 'Complications and safety' above.)
●After either talc insufflation or slurry, we suggest leaving the chest tube in place until fluid drainage is less than 150 mL per day rather than removal in the first 24 hours (Grade 2B).
