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* From the Division of Thoracic Surgery (Drs. de Campos and Cardoso), Pulmonary Division (Drs. Vargas, Werebe, Teixeira, and Jatene), University of San Paulo, Medical School, San Paulo, Brazil; and Vanderbilt University (Dr. Light), Nashville, TN.
Correspondence to: José Ribas Milanez de Campos, MD, Rua Almirante Soares Dutra n.520, 05654–000 São Paulo, Brazil; e-mail: jribas{at}usp.br
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Abstract |
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Methods: Six hundred fourteen consecutive patients (58.6% female; mean age, 54.5 years) underwent thoracoscopy with talc poudrage from August 1983 to May 1999. Of these, 457 patients had malignant pleural effusions, 108 patients had benign pleural effusions, and 49 patients had spontaneous pneumothorax.
Results: Sixty-four patients were excluded from evaluation for efficacy: 30 patients (4.9%) because the lung did not expand at the time of the procedure and 34 patients (5.5%) because they died within 30 days of the thoracoscopy. All exclusions were in the malignant group. The overall success rate of the 393 patients with malignant pleural effusions was 93.4%, while the overall success for the 108 patients with benign effusions was 97%, although 7 patients (7%) with benign effusions required a second thoracoscopy. The success rate with pneumothorax was 100%. Major morbidity included empyema in 4%, reexpansion pulmonary edema in 2.2%, and respiratory failure 1.3%.
Conclusion: Thoracoscopy with talc poudrage is effective in producing a pleurodesis in malignant and benign pleural effusion and in spontaneous pneumothorax. However, it should be noted that the insufflation of talc has a systemic distribution associated with a low rate of morbidity and perhaps does induce ARDS, which is sometimes fatal in a small percentage of patients. Because of these side effects, the search for a better agent should be continued.
Key Words: pleural effusion • pleurodesis • pneumothorax • talc poudrage • thoracoscopy • videothoracoscopy
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Introduction |
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We have been using talc insufflation in conjunction with thoracoscopy for the past 15 years to produce pleurodesis in patients with malignant or benign pleural effusions or spontaneous pneumothorax. Because there have been several reports6 7 8 9 10 regarding the possibility of significant side effects from talc, we decided to review our experience with emphasis on the efficacy and side effects of this procedure. The purpose of this study is to analyze efficacy, side effects, and mortality associated with talc poudrage pleurodesis during the last 15 years in a tertiary hospital.
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Materials and Methods |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Thoracoscopy was performed with a Carlen’s mediastinoscope (fifth intercostal space) in 359 patients (58.5%), and with video-assisted thoracic surgery with three ports (two in the fifth intercostal space and one in the eighth intercostal space) in 255 patients (41.5%). Pleural and pulmonary biopsies were performed when necessary, and pneumothorax was treated by resection of the bullae, when possible. Pleurodesis was produced using 2 g of asbestos-free talc or hydrated magnesium silicate (Mg3Si4O10 [OH]2) with a particle size of 5 to 70 µm (Sterifarma Lab; Sao Paulo, Brazil), which had been sterilized by autoclaving for 45 min at 270°F. After the procedure, one or two chest tubes (28F to 32F) were inserted as low as possible and removed when there was no air leak for 48 h or when fluid drainage was < 100 mL/24 h.
Treatment with a broad-spectrum antibiotic (cephalothin, 2 g) was started before the procedure and continued until the chest tubes were removed. Analgesics were administered when necessary. Chest radiography was performed shortly after the patient was admitted to the hospital, repeated on the second postoperative day, and at subsequent follow-up visits (every 3 months). For statistical analysis, the success of talc pleurodesis was defined as the absence of pleural fluid on the follow-up chest radiographs; any reaccumulation was regarded as a failure or recurrence. Patients were excluded when the lung did not expand after the procedure or if they died within 30 days of the talc pleurodesis. It is our policy and that of many others5 12 14 to not use talc when the lung is trapped.
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Results |
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One hundred eight patients with benign pleural effusions underwent thoracoscopy and talc insufflation. During the follow-up period of 1 to 84 months, 7 of 108 patients (6.5%) developed a recurrence of their pleural effusion and were submitted to a second thoracoscopy with talc insufflation. None of these seven patients had another recurrence. There were three patients in whom thoracoscopy did not control the pleural effusions. All three patients had part of their lung covered with fibrous tissue. One of these patients developed an empyema after talc insufflation, while the other two patients had a small residual space filled with fluid. Therefore, the latter two patients were labeled as failures even though they remained asymptomatic after the procedure. Consequently, 105 of 108 patients (97%) studied had an effective pleurodesis (Table 1) .
In the group of 158 patients with pleural effusions secondary to breast cancer, 21 patients were excluded, 5 patients because of death and 16 patients because of trapped lung. The mean follow-up period in the 137 patients studied was 12.1 ± 9.7 months (range, 1 to 42 months). There were five recurrences, yielding a success rate of 96.4%. In the group of 299 patients with other malignancies, 43 patients were excluded (29 patients because of death and 14 patients with trapped lung). The mean follow-up period in 256 eligible patients was 5.9 ± 3.0 months (range, 1 to 16 months). There were 17 recurrences (6.6%), with a success rate of 93.4% (Table 1) .
The morbidity observed after talc insufflation is shown in Table 3 . The most common morbidity was prolonged drainage, which we defined as lasting > 14 days (4% of patients). Empyema, a serious complication, occurred in 15 patients (4%), while pneumonia occurred in 4 patients (0.7%). Respiratory failure occurred in 7 patients (1.3%), while reexpansion pulmonary edema occurred in 12 patients (2.2%).
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Discussion |
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In the present study, effective pleurodesis was obtained in > 95% of 550 patients with benign or malignant diseases. All patients (100%) with recurrent pneumothorax and 97% of the patients with benign pleural effusion underwent successful pleurodesis with talc insufflation. The success rate with pleurodesis for patients with malignant pleural effusions because of breast carcinoma and malignant effusions because of other malignancies was > 90%.
In general, the percentage of patients who develop significant postoperative complications is low. In the present study, the talc insufflation administered in conjunction with thoracoscopy was well tolerated by almost all of the patients and most of the observed side effects were not of great clinical significance.
The most common side effect in the present series was prolonged drainage, which we defined as drainage maintained for > 14 days. This occurred in 4% of patients, and prolonged hospitalization occurred in at least some of these patients. Air leaks and postoperative bleeding are mainly related to the surgical manipulations, such as biopsies, and/or to the number of pleural adhesions found during the procedure. This is why, currently, our policy is to perform pleurodesis for recurrent pleural effusions as early as possible when the lung can expand fully and there are no pleural adhesions or marked pleural thickening.
The most significant side effects that our patients experienced were ARDS, occurring in 7 patients (1.3%), and reexpansion pulmonary edema, occurring in 12 patients (2.2%). Rinaldo et al6 reported the development of ARDS after application of 10 g of talc intrapleurally, with 250 mL saline solution (talc slurry), in three patients with malignant pleural effusions. The development of ARDS in these patients was attributed to the large dose of talc by some.16 However, ARDS can develop after much lower doses of talc, as shown in the present series and the report by Bouchama and associates.7 These latter workers described a patient who developed acute pulmonary distress syndrome with bilateral interstitial infiltrates and pleural effusion after a thoracoscopy with 2 g of insufflated talc (poudrage), in which two pleural biopsies were performed with a small amount of bleeding. BAL on the 12th postoperative day showed talc particles. It is possible that the biopsies allowed the talc particles to gain access to the circulation.
At the present time, the incidence of ARDS after intrapleural talc appears to be low, although Rehse and coworkers10 reported a 9% incidence of ARDS after 89 procedures with talc insufflation when combined with pleural abrasion. They call attention to "a significant higher rate of serious complications than that reported in the current literature, without implicating a clear reason for these outcomes." We observed the development of respiratory distress syndrome with bilateral interstitial infiltrates in seven patients (1.3%) of our series. Three patients reported previously9 died: the first was a 69-year-old man with squamous cell carcinoma and a malignant pleural effusion who underwent pleural and pulmonary biopsies before the talc insufflation. After 12 h, he developed acute respiratory failure, and the BAL 48 h after the procedure demonstrated talc particles. He died on the 30th postoperative day from persistent respiratory failure. The second patient was a 67-year-old woman with breast cancer, who developed acute respiratory failure 8 h after thoracoscopy with pleural biopsy. The BAL 6 days after the procedure showed talc particles. She died on the 43rd postoperative day from persistent respiratory failure. The third patient, with lymphoma of the mediastinum and bilateral chylothorax, underwent a pleural biopsy and concomitant bilateral talc pleurodesis. Ten hours later, he developed bilateral pulmonary infiltrates, hypoxemia, hypercapnia, hypotension, and mental confusion. After intubation and mechanical ventilation, talc crystals were found in BAL; 4 days later, he developed convulsions and died with diagnosis of ARDS. The autopsy demonstrated talc crystals in almost all organs, including the ipsilateral and contralateral lung, brain, liver, kidney, heart, spleen, and skeletal muscle.9 The amount of deposited talc was not quantitated. Four other patients also developed ARDS and required mechanical ventilation but subsequently recovered. All of these patients have a very limited lung function because of compression of pleural effusion, primary or metastatic cancer, and lymphangitic tumor spread in the lung parenchyma. None of our patients received steroids for treatment of ARDS.
The pathogenesis of ARDS after insufflation of talc intrapleurally is unknown. The most common theory is that ARDS is due to the effects of talc entering the systemic circulation. Many years ago, Karsner and Swanbeck17 postulated that intrapleural talc moves into the parietal pleural lymphatics and is transported to the mediastinal lymph nodes and thoracic duct, where it enters the systemic circulation. Subsequent studies in rabbits18 and rats19 have shown the systemic distribution of talc after it is administered intrapleurally. Werebe et al19 have shown a rapid absorption of talc particles through the pleura, which can be found shortly after the procedure in BAL and in target organs. It is not dose related, and they still cannot reach any further conclusion regarding clinical manifestations related to this phenomenon. Mitchem et al20 also demonstrated the distant sequelae, histologic changes in the contralateral lung, and serum enzyme elevations in rabbits, suggesting undesirable systemic effects. The one patient in the present series who died from ARDS and underwent autopsy had talc particles throughout his body. However, Kennedy et al18 have suggested that it is unlikely that the entry of only a small number of talc particles into the systemic circulation could have such devastating effects. Perhaps biopsy procedures and the affected pleural space allow access of a greater number of particles into the systemic circulation in certain individuals.
The observation that the incidence of ARDS varies markedly from series to series raises the possibility that there is something unique about some talc preparations that might lead to the induction of ARDS. Certainly the median particle size and the amount and type of mineral impurities vary markedly from one talc preparation to another.21 Another possible explanation is the contamination of some talc preparations by endotoxin of some other impurity, which could elicit ARDS.
A noncardiac pulmonary edema is sometimes observed after lung reexpansion after collapse because of pneumothorax or pleural effusion. This reexpansion pulmonary edema is usually unilateral, but it may be bilateral. In an occasional patient, it may be severe enough to require mechanical ventilation22 and can cause death in young otherwise healthy individuals.23 When reexpansion pulmonary edema is bilateral, it is virtually impossible to differentiate from the ARDS because of talc. Prolonged duration of collapse and rapid reexpansion of the lung because of application of negative pressure have been cited as factors that predispose to formation of edema.24
In the present series, 12 patients (2.2%) developed reexpansion pulmonary edema. The total fluid drained during thoracoscopy in 11 patients was always > 3,000 mL (range, 3,200 to 5,000 mL), and the 12th patient had six episodes of pneumothorax. For patients with large pleural effusions, we recommend one or two therapeutic thoracenteses before thoracoscopy, with the drainage of at least 1,500 mL at each procedure, and also to evaluate lung expansion. No mortality in this group was noted and no procedures were performed under local anesthesia; however, most of these patients needed mechanical ventilation in the ICU.
According to Ohri et al,5 the risk of infection with thoracoscopy and talc insufflation is low. These authors observed an incidence of only 0.43% in a collected series of 1,145 patients undergoing thoracoscopy. In the present series, the incidence of empyema was 2.5%. Less than 1% of our patients developed either pneumonia (0.7%) or infection at the site of the chest tube insertion (0.5%). These infections occurred despite the administration of antibiotic medications before and after the procedure.
Fever is usually defined as a transient rise in body temperature to > 37.7°C. Moreover, Viallat et al25 observed in 9.8% of patients temperatures > 38.5°C that lasted 1 day. The true incidence of fever after thoracoscopy with talc insufflation is unknown. In our series, a temperature between 37.7°C and < 38.5°C was observed in 15 of 547 patients (2.8%) without any evidence of infectious disease. No temperature > 38.5°C was observed, and fever occurred during the first 2 postoperative days and disappeared spontaneously after the third day.
Sorensen and coworkers26 in 1984 reported persistent pleural pain after talc pleurodesis. According to Viallat and associates,25 this symptom was invariably present during the first 24 h after the pleurodesis procedure and was treated depending on the individual patient’s needs. However, in our 547 patients, only 11 patients (2.0%) developed chest pain during the postoperative period, and in 3 of them, the procedure was done with local anesthesia and IV sedation. In our opinion, the chest tube rather than the talc poudrage is the main factor that produces the pain. Prescribing analgesics for the first 24 h in general minimizes this problem.
It is important not to subject patients with advanced malignancy who
are malnourished and who have Karnofsky performance scores of 
40 to
thoracoscopy with talc insufflation. Many of the deaths early in our
series occurred in patients such as these. There is little reason to
perform thoracoscopy and talc poudrage on the patient who has a very
limited life expectancy (< 30 days) or substantially compromised
cardiorespiratory reserve. In our malignant series, the prolonged
drainage (17 patients; 4.4%) and mortality (34 patients; 7.4%)
reflect the initial policy of attempting talc poudrage in patients with
much more advanced disease than those who we now accept for the
procedure.
Currently, debilitated patients or those with advanced disease, malnourishment, or coexisting diseases in other organ systems must be submitted to a strict selection to differentiate them from a group of terminally ill patients. In such patients, we recommend serial thoracentesis and/or small chest tubes with the injection of talc slurry to manage the pleural effusion.
In the past, there was concern that asbestos could lead to the development of malignant mesothelioma and a progressive pleural thickening with loss of pulmonary function. Paul and associates27 in 1951 studied lung function after talc pleurodesis in the management of recurrent spontaneous pneumothorax and concluded that it did not produce any demonstrable harmful effects during the observation period of their patients. Lange and coworkers28 observed a mild restrictive impairment of lung function after talc poudrage without the development of mesothelioma during a period of 22 to 35 years. In addition, the Research Committee of the British Thoracic Association and the Medical Research Council Pneumoconiosis Unit29 presented a survey on the long-term effects of talc pleurodesis 14 to 40 years after the initial pleurodesis and found no increase in lung cancer and no case of mesothelioma reported.
In 1969, Jackson and Bennett30 reported that 2 years after talc pleurodesis for spontaneous recurrent pneumothorax, a patient developed a chest wall adenocarcinoma, probably a "scar carcinoma." Tumoral seeding at the site of thoracoscopy ports and/or on the drainage line occurs in 2 to 4% of patients.4 31 Johnstone et al,32 in a review article, reported 21 incidents of port site recurrences, related by 48 responding surgeons of the Video-assisted Thoracic Surgery Study Group. In our series, only three (0.5%) patients developed tumoral implants, and these patients were successfully treated with local radiotherapy.
In the beginning of our experience, we also agreed with the words of Weissberg,16 "when used with proper care and attention to technical detail, it should produce solid pleural adhesions in > 90% of patients and cause virtually no complications." Ultimately, we conclude that talc is one of the cheapest and most reliable agents to promote pleural symphysis, but we are concerned about its side effects. This study demonstrates that the intrapleural insufflation of 2 g of talc at the time of thoracoscopy is a very effective means of preventing the recurrence of benign or malignant pleural effusion or pneumothorax. In the present series, recurrences occurred in 2% of patients with pneumothorax, 9.2% of those with benign effusions, 3.6% with breast cancer, and 6.6% with other malignancies. However, despite its efficacy, even with a low morbidity rate, concerns remain about its safety, primarily because of the instances of ARDS and the systemic effects that have been reported after its administration intrapleurally.
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Acknowledgements |
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Received for publication January 21, 2000. Accepted for publication October 5, 2000.
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