Annals of Surgical Oncology

, Volume 16, Issue 3, pp 745–750

Bedside Talc Pleurodesis for Malignant Pleural Effusion: Factors Affecting Success

Authors

    • Department of Third Thoracic SurgeryYedikule Teaching Hospital for Chest Diseases and Thoracic Surgery
  • Servet Ozdemir
    • Department of Third Thoracic SurgeryYedikule Teaching Hospital for Chest Diseases and Thoracic Surgery
  • Levent Cansever
    • Department of Third Thoracic SurgeryYedikule Teaching Hospital for Chest Diseases and Thoracic Surgery
  • Yasar Sonmezoglu
    • Department of Third Thoracic SurgeryYedikule Teaching Hospital for Chest Diseases and Thoracic Surgery
  • Celalettin Ibrahim Kocaturk
    • Department of Third Thoracic SurgeryYedikule Teaching Hospital for Chest Diseases and Thoracic Surgery
  • Mehmet Ali Bedirhan
    • Department of Third Thoracic SurgeryYedikule Teaching Hospital for Chest Diseases and Thoracic Surgery
Thoracic Oncology

DOI: 10.1245/s10434-008-0263-x

Cite this article as:
Aydogmus, U., Ozdemir, S., Cansever, L. et al. Ann Surg Oncol (2009) 16: 745. doi:10.1245/s10434-008-0263-x

Abstract

Introduction

To determine the factors affecting the success of bedside talc slurry (TS) used for symptomatic treatment of patients with malignant pleural effusion (MPE).

Methods

Data of 113 effusions in 103 MPE patients treated between 1999 and 2007 were retrospectively evaluated for the study. The study group involved 73 patients whose follow-up information was available out of 81 patients treated by TS. Causes of MPE were lung cancer in 22 patients (30.1%) and breast carcinoma in 21 patients (28.8%).

Results

The success rate of TS was significantly higher if the time period between radiological diagnosis of effusion and administration of TS was less than 30 days (P = .02), or spontaneous expansion was attained after chest tube drainage (CTD) (P = .01). Success rate was higher for patients with daily drainage of less than 200 ml before TS than patients with more than 200 ml of daily drainage (P = .01). Dose of talc, either 4 g or above (P = .34), primary cause of MPE (P = .53), time to termination of CTD (P = .57), amount of drainage when CTD was terminated (P = .23), and time period between CTD and administration of TS (P = .20) did not show a statistically significant effect on the success of TS.

Conclusion

In the treatment of malignant pleural effusion, patients with daily drainage of less than 200 ml before TS developed less recurrence than patients with daily drainage of more than 200 ml. Longer time period between the diagnosis of MPE and onset of CTD increased recurrence.

Patients with malignant pleural effusion (MPE) show limited survival rates.1,2 Most cases experience symptoms such as dyspnea that disturb quality of life.1,3 Pleurodesis that obliterates the pleural cavity is employed to alleviate dyspnea and to improve the quality of life.3,4 Performance status of the patient, type of primary tumor that caused malignant effusion, and re-expansion of lung after drainage of effusion are some of the factors that define the method of pleurodesis.3 Talc slurry (TS) that can be administered at the bedside offers low cost without the need for anesthesia and operation room.5

Recent studies have usually compared the methods of pleurodesis or the agents used. This study investigated the factors that affected the success of bedside TS administered through chest tube to attain pleurodesis in patients with MPE.

Patients and Methods

Data of 103 patients diagnosed as symptomatic MPE and selected for palliative treatment between 1999 and 2007 were retrospectively evaluated. Ten patients had synchronous or metachronous bilateral MPE; thus procedures performed for a total of 113 effusions were documented. Out of 81 patients treated by TS, 73 patients whose follow-up information 30 days after TS was available formed the study group (Fig. 1).
https://static-content.springer.com/image/art%3A10.1245%2Fs10434-008-0263-x/MediaObjects/10434_2008_263_Fig1_HTML.gif
Fig. 1

The treatment and results for overall patients with malignant pleural effusions. MPE malignant pleural effusion, TS talc slurry; ALI acute lung injury

Chest tube drainage (CTD) was performed for all patients except two cases that could not be diagnosed by videothoracoscopic pleural biopsy and therefore underwent pleurectomy for differential diagnosis and pleurodesis. Bedside chemical pleurodesis was performed for 86 cases (77.5%); “asbestos-free” sterile talc was used in 81 cases (94.2%). Eight of the patients (7.1%) for whom pleurodesis was not performed died of advanced disease. Other than two cases directly selected for pleurectomy, three cases (2.7%) with daily drainage of more than 300 ml after CTD and two cases (1.8%) that showed partial expansion defect also underwent pleurectomy. Long-term CTD was preferred because of high amounts of daily drainage or re-expansion defect in five cases (4.4%), and because of empyema in three cases (2.7%). Finally, four cases (3.5%) in which pleurodesis could not be performed due to incomplete re-expansion were scheduled for therapeutic thoracentesis and followed in the outpatient clinic (Fig. 1). The study group involved 73 patients whose follow-up information were available out of 81 patients treated by TS.

The mean age of the patients was 57.5 years (range 26–85 years); 39 of them (53.4%) were women, and 34 of them (46.6%) were men. Most common causes of MPE were lung cancer in 22 patients (30.1%) and breast carcinoma in 21 patients (28.8%) (Table 1).
Table 1

Primary tumor site in patients with malignant pleural effusion

Primary tumor site

Overall patients with MPE

The study group

n

%

n

%

Lung

36

31.9

22

30.1

Breast

31

27.4

21

28.8

Genitourinary tract

10

8.8

6

8.2

Gastrointestinal tract

3

2.7

2

2.7

Mesothelioma

5

4.4

2

2.7

Other

11

9.7

9

12.3

Unknown primary

17

15.0

11

15.1

Total

113

100

73

100

MPE denotes malignant pleural effusion

Chest tubes ranging between 24 and 28 Fr or small-diameter (8–10 Fr) closed thoracic catheter system were used depending on the performance status and the appearance of thoracentesis fluid of each case. A small-diameter catheter was used for patients who had serous (not viscous) thoracentesis fluid and for the cases in which the Karnofsky scale was below 70. A chest tube was used if re-expansion of the lung could be provided after introduction of small-diameter catheter. Re-expansion of the lung was the crucial prerequisite to use chemical pleurodesis administered via drainage system. If the patient had a leak during inspiration or the patient’s lung was not completely re-expanded, chemical pleurodesis was not applied and −20 cm H2O pressure was applied.

Pethidine HCl at a dose of 50 mg was administered intramuscularly 30 min before administration of talc. Talc slurry was prepared by 4–8 g of sterile talc, 150 mg lidocaine, 5 mg bupivacaine, and up to 60 ml of 0.9% NaCl solution at room temperature and was administered through the drainage system. After slurry, an additional 40 ml of 0.9% NaCl solution was administered. TS was administered via thoracostomy tube in 67 cases (91.8%) and through 8–10 Fr closed drainage system in 6 cases (8.2%). The drainage system was clamped for 4 h after administration of TS, and patients were asked to change their positions frequently. After administration of TS, −20 cm H2O pressure was routinely applied to all patients with thoracostomy tubes for at least 24 h. Drainage was ceased if drained fluid was less than 200 ml in 24 h.

Patients were followed weekly by posteroanterior chest radiographies within 3 weeks after discharge. Success was defined as the absence of effusion within 3 weeks after termination of drainage. Partial response was defined as localized effusion that did not progress, cause symptoms, or require drainage. If the volume of collected fluid was large or patient was dyspneic, a second chest tube or catheter was applied, and if daily drainage from the CTD was more than 100 ml/day, talc was administered for a second time. Success was defined as no recurrence of the effusion for patients drained a second time. Absence of effusion was also defined as success for the patients that received talc twice due to daily drainage of more than 200 ml after the first administration of talc.

Primary cause of effusion, time period between the onset of effusion and drainage by chest tube, dose of talc, method of administration (small catheter or chest tube), requirement of negative pressure for complete expansion of lung, time period between drainage and TS, amount of daily drainage before TS, amount of daily drainage when chest tube or catheter was removed, and the date of removal of drainage after administration of talc was recorded (Table 2).
Table 2

The factors that affected the success of bedside talc slurry

Factors

Successful

Unsuccessful

Univariate P value

Multivariate P value

n

%

n

%

Primary tumor site

    Lung

16

72.7

6

27.3

.17

.54

    Non-lung

44

86.3

7

13.7

  

Talc dosage (g)

    ≤4

25

86.2

4

13.8

.34

 

    ≥4

35

79.5

9

20.5

  

Time period between diagnosis of effusion and CTD (days)

    

.02

.05

    ≤30

38

92.7

3

7.3

.06

.02

    30–90

14

73.7

5

26.3

  

    >90

8

61.5

5

38.5

.36

.49

The amount of daily drainage before TS (ml)

    

<.001

.01

    ≤100

48

88.9

6

11.1

.49

.33

    100–200

11

84.6

2

15.4

  

    >200

1

16.7

5

83.3

.01

.01

The spontaneous expansion occurred after drainage

    Suction required

8

50.0

8

50.0

.001

.01

    Spontaneous expansion

52

91.2

5

8.8

  

Time period between CTD and TS (days)

    ≤5

45

90.0

5

10.0

.015

.21

    >5

15

65.2

8

34.8

  

The methods of CTD

    Large bore catheters (24–28 Fr)

54

80.6

13

19.4

.29

 

    Small bore catheters (8–10 Fr)

6

100

0

   

The amount of 24-h drainage before withdraw CTD (ml/day)

    ≤100

57

95.0

3

5.0

.23

 

    100–200

3

75.0

1

25.0

  

Time period between TS and withdraw CTD

    ≤48 h

45

95.7

2

4.3

.57

 

    >48 h

15

100

0

   

CTD denotes chest tube drainage; TS denotes talc slurry

Statistical Analysis

Variables were categorized after frequency, mean, and standard deviations were calculated for descriptive parameters. Frequency of variables was compared by chi-square test. Fisher exact test was used to compare small groups. Mann–Whitney U test was used to compare numeric values. Logistic regression test was used for multivariate analysis if P value was less than .2, and P value less than .05 was considered significant.

Results

A successful outcome was achieved in a total of 60 MPE cases (82.2%). Of these, 49 cases (81.7%) were completely successful, and 11 (18.3%) showed a partial response. Eleven cases (15.1%) required a second administration of talc as a result of a high amount of drainage after the first administration of talc. Five patients (45.5%) who did not develop effusion after the second talc pleurodesis were also designated as successfully treated. Pleurodesis failed in 13 patients: two of them (15.4%) showed recurrent effusion after termination of CTD; long-term CTD was used for three cases (23.1%) due to empyema and for five cases (38.5%) due to daily drainage of more than 200 ml. Three patients (23.1%) were scheduled for therapeutic thoracentesis due to a high amount of daily drainage. Hypoxia or acute lung injury (ALI) was observed in five patients (6.2%) after administration of talc; two of them (2.5%) died.

The mean time period between CTD and TS was 5.0 days (ranging from 1 to 18 days). The time period between drainage and TS was more than 5 days in 23 patients (31.5%). The causes of the delay was high amount of daily drainage in five cases (21.7%), prolonged air leak in four cases (17.4%), and lack of complete re-expansion in 14 cases (19.2%). CTD was terminated within a mean of 2.4 ± 2.1 days, or within 1–5 days after administration of TS for all patients except one who developed infection and whose CTD was terminated at the 17th day. The mean amount of daily drainage was 96 ml/day (range 0–600 ml/day) before TS. The mean amount of daily drainage was 30 ml/day (range 0–200 ml/day) when CTD was terminated.

No statistically significant difference was observed between the patients who developed MPE because of primary lung carcinoma and because of other causes in terms of the time period between CTD and TS (P = .10), CTD remaining time after TS (P = .98), requirement for negative pressure after CTD (P = .33), and time period between diagnosis of effusion and CTD (P = .47) (Table 3).
Table 3

The site of primary tumor in patients with malignant pleural effusion compared with the MPE patients of other causes

Characteristics

Lung (n = 22)

Non-lung (n = 51)

P value

Successful pleurodesis

16

72.7%

44

86.3%

.17

Spontaneous re-expansion

16

72.7%

41

80.4%

.33

Time period between CTD and TS (day)

6.3 ± 4.7

4.5 ± 3.3

.10

Time period between TS and withdraw CTD (day)

2.1 ± 0.4

2.5 ± 2.4

.98

Time period between diagnosis of effusion and CTD (day)

48.3 ± 48.0

56.4 ± 109.4

.47

CTD denotes chest tube drainage; TS denotes talc slurry

Univariable analysis showed that TS treatment was more effective if the primary cause of effusion was extrapulmonary (P = .17), if the time period between radiological diagnosis of effusion and CTD was rather short (P = .02), if amount of daily drainage before TS was relatively low (P < .001), or spontaneous expansion occurred after drainage of pleural fluid (P = .001), or if time period between CTD and TS was less than 5 days (P = .015). Dose of talc, time to termination of CTD after administration of talc, method of CTD, or amount of daily drainage whether less than 100 ml or between 100 and 200 ml were not statistically significant factors to affect the success of TS (Table 2).

Multivariate analysis showed that success rate was higher if the time period between radiological diagnosis of effusion and TS was less than 30 days (P = .02), or if spontaneous expansion occurred after drainage of pleural fluid (P = .01). The amount of daily drainage before TS, whether less than 100 ml or between 100 and 200 ml was not statistically significant (P = .33). However, success rate of patients with daily drainage of less than 200 ml was higher compared with patients with daily drainage of more than 200 ml (P = .01). No significant difference was observed between the patients who have lung carcinoma as the primary cause of MPE and other causes of MPE (P = .54) and also between the patients who had a time period between CTD and TS of less than 5 days and those who had more than 5 days.

Discussion

Patients with malignant pleural effusion (MPE) show limited survival rates.1,2 The majority of these patients suffer from progressive dyspnea that mandates treatment.6 Pleurodesis may be performed for selected patients to reduce dyspnea and improve the quality of life.3,4 Repeated thoracentesis or chemical pleurodesis through videothoracoscopy or through chest tubes are the alternative methods for palliative treatment.4,7 Performance status of the patient, primary disease, and re-expansion of the lung are the important points to assess for deciding the method of treatment.2 Chemical pleurodesis performed together with tube drainage helps to reduce the symptoms in the majority of MPE patients with low cost and low morbidity.5,6 Talc seems to be more successful and reliable among other chemical agents.3,8,9 Bedside administration of TS does not require general anesthesia.5

There are reliable guides such as British Thoracic Society (BTS) guide that can be used to make a decision for the treatment of MPE patients.2 Success rate for TS has been reported to range between 80% and 100%.2,5 However, factors that define success in MPE patients are not clearly defined. For example, it is stated that the daily amount of drainage should be low before administration of TS.6 However, what is the critical limit? This study has shown that success rate of TS is reduced if the amount of daily drainage is more than 200 ml. Additionally, termination of CTD either before or after 48 h following administration of TS and the amount of daily drainage when CTD was terminated (as far as it is lower than 200 ml/day) had no effect on success rate. Some studies have demonstrated that dose and size of the talc particles increase the risk of ALI.2,4 Our results showed that dose of talc did not affect the outcomes. In our study, respiratory insufficiency developed in 2.3% of the patients after administration of TS, which was consistent with the literature. This figure ranges between 1.3% and 9.0% in the literature.10,11

Re-expansion of the lung is required to administer TS after removal of pleural fluid.2,6 Application of negative pressure to drainage bottles of patients with incomplete re-expansion may help to reduce pleural space by time. This study is the first to demonstrate that success of TS is higher in cases that show spontaneous re-expansion of lung. For patients who were suggested to have MPE by radiology, follow-up is recommended if they remain asymptomatic after thoracentesis.2 We observed that success was significantly decreased if time between the first diagnosis of effusion and onset of CTD is longer than 30 days; this may be explained by progression of pleural disease or fibrosis of the visceral pleura. Similarly, success was lower if time between CTD and TS was longer than 5 days, although not statistically significant.

Success of pleurodesis in MPE may also be related to primary disease. Both Stefani et al.,12 and DeCampos et al.10 have reported higher success rates for pleurodesis among patients with breast cancer, and lower success rates among patients who developed MPE as a result of lung carcinoma.13,14 Prevention of complete lung expansion due to endobronchial lesions may be the cause of lower success rate in MPE due to primary lung cancer. In our study, MPE cases due to lung cancer showed lower success compared with the MPE patients of other causes, but the difference was not statistically significant.

Both the review from Tan et al. and the BTS guide have stated that pleurodesis performed through either catheters of small diameter or through chest tubes with large diameter provide similar results.2,3 In our study, we did not determine a statistically significant difference between the success rates of these groups. However, comparison of two groups may not be appropriate as we have preferred small-diameter catheters for patients who had serous thoracentesis fluid.

Our study has the limitations of a retrospective study, as we were not able to document biochemical analysis of the pleural fluid for each case. However, we believe that analysis of the differences observed during the pleurodesis empowers our study. However, the number of failures after pleurodesis is relatively low; thus parameters determined as indicators of failure must be tested in larger series.

Talc slurry is an economic and safe method for symptomatic treatment of MPE. We determined that success of TS is considerably decreased if the amount of daily drainage is more than 200 ml and if suction is required for re-expansion of lung. It may be more appropriate to rapidly switch to alternative methods for patients with delayed re-expansion and a high amount of daily drainage. Warren et al.15 have reported excellent results with small-diameter catheters for the palliative treatment of these patients. We rather prefer long-term drainage and pleurectomy in patients with a high amount of daily drainage. Therapeutic thoracentesis and long-term drainage seem to provide fast treatment of patients with re-expansion defects. Pleuroperitoneal shunt is another effective alternative for these patients.2

In conclusion, success of TS decreases as time to onset of CTD is prolonged after diagnosis of MPE. Thus, early drainage with proper intervention followed by pleurodesis is recommended for the treatment of patients with MPE.

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© Society of Surgical Oncology 2008