Should Thoracoscopic Talc Pleurodesis Be the First Choice Management for Malignant Pleural Effusion? No
CHEST / 142 / 1 / JULY 2012
alignancy is one of the most common causes of exudative pleural effusion, with approximately 200,000 cases occurring annually in the United States.1 Many patients with malignant effusions have the quality of their life diminished by shortness of breath. If the shortness of breath is relieved with a therapeutic thoracentesis, then consideration should be given to proceeding with a procedure that will prevent the accumulation of pleural ﬂuid. If the patient is not symptomatic from the pleural effusion, no treatment is recommended. Most patients who have small effusions that do not produce symptoms never become symptomatic.2
The best way to prevent the accumulation of pleural ﬂuid is not known. In general, the two main procedures available are the implantation of an indwelling pleural catheter and the creation of a pleurodesis. A pleurodesis is created when an inﬂ ammationproducing material is injected into the pleural space. This can be done either through a chest tube or at the time of thoracoscopy. Agents used to produce the pleural inﬂammation include talc, tetracycline derivatives, silver nitrate, povidone, and antineoplastics.
In general, there are three components to this editorial. First, is pleurodesis superior to the implantation of an indwelling pleural catheter? Second, is pleurodesis in conjunction with thoracoscopy superior to pleurodesis done with tube thoracostomy? Third, is talc superior to the other agents in producing a pleurod esis?
Is pleurodesis superior to the implantation of an indwelling pleural catheter? The original study concerning the indwelling pleural catheter randomized 144 patients with symptomatic pleural effusions to receive an indwelling pleural catheter with intermittent drainage every 48 h, or doxycycline pleurodesis.3 These authors concluded that the indwelling pleural catheter was advantageous because it did not necessarily require hospitalization. Tremblay et al 4 subsequently reported a series of 250 tunneled pleural catheter insertions in 223 patients. Most of the catheters were inserted on an outpatient basis, and 90.1% of the patients required no further ipsilateral pleural procedures.4 They concluded that the indwelling catheter should be considered a ﬁ rst-line treatment option in the management of patients with malignant pleural effusion.4 Warren et al 5 reported a series of 231 indwelling catheters in 202 patients, of which 210 catheters were inserted as outpatients. They reported that they were able to remove 58% of the catheters, and reaccumulation of pleural ﬂ uid occurred in only ﬁve of these 134 patients (3.8%). 5 Van Meter et al 6 recently reviewed 19 studies with 1,370 patients who were treated with tunneled pleural catheters for malignant pleural effusion. They reported that symptomatic improvement occurred in 95.6% of patients, and spontaneous pleurodesis occurred in 45.6%. Serious complications were rare and included empyema in 2.85%. They concluded that prospective randomized studies comparing the tunneled indwelling catheter with pleurodesis are needed before the indwelling catheter can be recommended deﬁnitively as a ﬁrst-line treatment of malignant pleural effusion. A recent study compared the number of in-hospital days in 34 patients who elected to receive the indwelling catheter and 31 patients who elected talc pleurodesis.7 They reported that the median number of hospital days was signiﬁ cantly greater in the pleurodesis group (18 days) than in the indwelling pleural catheter group (6.5 days). Moreover, the median number of hospital days related to the effusions was signiﬁcantly greater in the pleurodesis group (10 days) than in the indwelling pleural catheter group (3 days). The patients in the indwelling catheter group also spent a smaller percentage of their remaining lives (8.0%) in the hospital, compared with the pleurodesis group (11.2%). Thus, it appears that implantation of an indwelling catheter is a viable option for the treatment of a malignant pleural effusion.
Figure 1. Time to recurrence of malignant pleural effusion in patients receiving talc slurry and talc insufflation. Note that the lines are nearly superimposable, with talc slurry having a slight advantage. (Reproduced with permission from Dresler et al.8)
If a pleurodesis is attempted, are the results with thoracoscopy superior to those with tube thoracoscopy? The largest randomized controlled study on this subject was reported by Dresler et al.8 In this multicenter study, 482 patients were randomized to receive 4 to 5 g of talc , either administered as a slurry in 100 mL saline through a chest tube or insufﬂated during thoracoscopy. The Kaplan-Meier curves for the proportion of patients with a recurrence were essentially superimposable with a very slight advantage to the group that received the slurry ( Fig 1 ). 8 In this study, subgroup analysis showed that patients with lung or breast carcinoma who were treated with thoracoscopy had a lower recurrence rate (18%) at 30 days than did patients treated with tube thoracostomy (33%). The only other randomized study9 that I am aware of that compared thoracoscopy with tube thoracostomy also concluded that thoracoscopic talc insufﬂation was not superior to talc slurry in the management of symptomatic malignant pleural effusion. This smaller study randomized 57 patients to one of the two treatments and reported that there was no difference in recurrence, chest drainage duration, or complications between the two groups.9 Because talc insufﬂation requires more resources, they concluded that talc slurry should be considered as the procedure of choice in the treatment of symptomatic malignant pleural effusion in patients who do not have a trapped lung.9 However, if the diagnosis of malignancy is made at thoracoscopy, then it is reasonable to inject a sclerosant in an attempt to create a pleurodesis.
If pleurodesis is attempted, what agent should be used? Talc is the sclerosing agent most commonly used for chemical pleurodesis by pulmonologists in English-speaking countries.10 The reason that talc is the most popular agent is that it is widely available, inexpensive, and perceived to be effective. However, as seen in Figure 1 , talc is not overwhelmingly effective, because by 50 days .30% of the patients had a recurrence. Many different agents have been injected intrapleurally in attempts to create a pleurodesis, including the tetracycline derivatives,1 silver nitrate,11 iodopovidone,12 and bleomycin.1 There is no convincing evidence that talc is superior to other agents, because there have been very few randomized controlled studies comparing the different agents.
One concern about talc is that its intrapleural administration has been associated with the development of ARDS and death in some patients. The incidence of ARDS has varied markedly from series to series, and most of the reported cases have been from the United States. There were 13 respiratory deaths in the 449 patients (2.9%) in the study by Dresler et al8 discussed previously. Maskell et al13randomized 20 patients with malignant effusions to receive 20 mg/kg tetracycline or 4 g of mixed talc, with most particles ,15 mm. They reported that the patients who received mixed talc had a signiﬁ cantly greater decrease in diethylene triamine pentaacetic acid clearance, a signiﬁcantly greater decrease in arterial oxygen saturation, and a signiﬁ cantly greater increase in C-reactive protein.12 It appears that acute lung injury depends on the size of the talc used. Maskell et al13 randomized 48 patients to receive mixed talc or graded talc in which most particles ,15 mm had been removed. They reported that the patients who received the graded talc had a significantly smaller increase in the alveolar to arterial oxygen gradient, a signiﬁcantly smaller decrease in Pa o2 , and a signiﬁcantly smaller increase in C-reactive protein. Janssen et al , 14 in a multicenter, open-label, prospective cohort study of 558 patients who received 4 g calibrated French large-particle-sized talc for malignant effusion, reported that there were no instances of ARDS. However, seven patients did develop pulmonary inﬁltrates, which they attributed to reexpansion pulmonary edema in two, cardiogenic pulmonary edema in one, and respiratory failure unrelated to talc in one.13 I am not convinced that the pulmonary inﬁltrates in some of these patients were not related to the talc. In general, if one elects to use talc as a pleurodesing agent, only large-sized talc should be used.
In summary, the indwelling pleural catheter is a reasonable alternative to pleurodesis in many patients and appears to be associated with fewer days in hospital. There is no good evidence that pleurodesis via thoracoscopy is any more effective than pleurodesis via tube thoracostomy. Talc is the agent used most commonly for pleurodesis, but only large-particle talc should be used. Reasonable alternatives to talc are the tetracycline derivatives, silver nitrate and iodopovidone. Randomized controlled studies are needed to identify the optimal way to manage patients with symptomatic malignant pleural effusions.
Richard W. Light, MD, FCCP Nashville, TN
Afﬁ liations: From the Division of Allergy, Pulmonary, Immunology and Critical Care, Vanderbilt University. Financial/nonﬁ nancial disclosures: The author has reported to CHEST the following conﬂicts of interest: Dr Light has been on the advisory board of and is a consultant to CareFusion, which makes the Pleurx indwelling catheter, and CareFusion has provided support for some of his speaking engagements . Correspondence to: Richard W. Light, MD, FCCP, Vanderbilt University, 2201 W End Ave, Nashville, TN 37235 ; e-mail: rlight98@ yahoo.com © 2012 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.
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