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Comparison of insufflated talc under thoracoscopic guidance with standard tetracycline and bleomycin pleurodesis for control of malignant pleural effusions
Comparison of insufflated talc under thoracoscopic guidance with standard tetracycline and bleomycin pleurodesis for control of malignant pleural effusions The standard paUiation of malignant pleural effusions involves tube thoracostomy drainage with chemical pleurodesis. The insufflation of intrapleural talc under thoracoscopic guidance (n = 39) was evaluated against documented controls that consisted of patients (n = 85) who participated in a randomized study with tube thoracostomy drainage followed by either bleomycin or tetracycline sclerosis. Under local anesthesia, which was supplemented by intravenous sedation, patients in the talc group underwent complete pleural fluid evacuation. The talc was then insufflated evenly on the entire pleural surface under thoracoscopic guidance. Of the patients in the talc group who survived their disease process, 97 % had a successful pleurodesis at 30 days and 95 % at 90 days. In comparison, the bleomycin group demonstrated a success rate of 64 % at 30 days and 70 % at 90 days (p = 0.003 and p = 0.047 versus the talc group). The tetracycline group had successful pleurodesis in only 33 % at 30 days and 47% at 90 days (p < 0.001 and p < 0.001 versus the talc group). There were only two patients in the talc group in whom pleurodesis was not successful, and both were subsequently found to have extraluminal compression of the right lower lobe bronchus, which prevented lung reexpansion. These data demonstrate that the insufflation of talc into the pleural cavity under thoracoscopic guidance is a safe and efficacious procedure in the control of malignant pleural effusions. (J THoRAc CARDIOVASC SURG 1993;105:743-8)
Daniel L. Hartman, MDa (by invitation), James M. Gaither, MDa (by invitation), Kenneth A. Kesler, MD b (by invitation), Deborah M. Mylet, RNa (by invitation), John W. Brown, MD,b and Praveen N. Mathur, MB, BSa (by invitation), Indianapolis, Ind.
Symptomatic malignant pleural effusions are caused by a variety of frequently incurable tumors that involve the pleural surfaces. As many as 50% of patients with breast and lung cancer will have a pleural effusion during the course of their disease. I Numerous methods/ have been advocated to induce pleurodesis, but no therapy has been consistently demonstrated to be superior.
From the Divisions of Pulmonary and Critical Care," Department of Medicine, and Cardiothoracic Surgery," Department of Surgery, Indiana University School of Medicine, Indianapolis, Ind. Read at the Seventy-second Annual Meeting of the American Association for Thoracic Surgery, Los Angeles, Calif., April 26-29, 1992. Address for reprints: Praveen N. Mathur, MB, BS, Division of Pulmonary and Critical Care, Department of Medicine, WOP 439 C, 100I West 10th St., Indianapolis, IN 46202. Copyright
1993 by Mosby-Year Book, Inc.
0022-5223/93 $1.00
+ .10
12/6/43347
In North America, the most widely accepted treatment of malignant pleural effusions includes initial tube thoracostomy drainage for a variable period of time, followed by instillation of tetracycline to achieve a chemical pleurodesis.l-:' This form of therapy, however, has a significant prevalence of morbidity, which includes pain 1,4 and, not infrequently, treatment failures that require additional therapy' Talc has been applied directly to the pleural surfaces after open thoracotomy'-? to achieve successful pleurodesis. However, this technique has never become popular because a prolonged recovery is necessary in patients with limited life expectancies. Boutin, Viallat, and Cargnino" have demonstrated that insufflated talc may be introduced into the pleural space by modern thoracoscopic techniques with minimal morbidity. We performed this study to evaluate talc insufflation under thoracoscopic guidance as a potentially more effective treatment of symptomatic malignant pleural effusions with a lower morbidity rate. 743
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Hartman et al.
Table I. Primary malignancy sites in evaluable patients Primary site Lung
Breast Ovary Other
talc
Bleomycin
Tetracycline
13 (39%) 8 (24%) 4 (12%) 8 (24%)
13 (36%) 9 (24%) 1(3%) 15 (39%)
13 (36%) 10 (28%) 2 (6%) II (31%)
Number of patients per site and percentage of treatment group (in parentheses). There was no significant statistical difference between the treatment groups (p = 0.63).
Patients and methods Study design. This was a prospective phase II open-label study that evaluated talc insufflation under thoracoscopic guidance as compared with documented controls." This control group consisted of patients who participated in a multicenter randomized study, which involved our institution and which evaluated tube thoracostomy drainage that was followed by either bleomycin or tetracycline chemical sclerosis. Successful pleurodesis was defined in all treatment groups as showing no reaccumulation of pleural fluid as determined by serial roentgenograms of the chest compared with roentgenograms before removal of the tube thoracostomy. Pleurodesis was considered unsuccessful if chest roentgenograms confirmed reaccumulation of pleural fluid. Follow-up visits that included roentgenograms of the chest were made at 30 and 90 days. Talc group. We performed thoracoscopic talc pleurodesis in 39 patients (20 men and 19 women), whose ages ranged from 41 to 88 years (mean, 58.8), with malignant pleural effusions as a result of a variety of primary malignant tumors (Table I). Patients were included in this prospective study if they met the following criteria: (I) dyspnea that improved after large-volume thoracentesis with subsequent recurrence of a symptomatic pleural effusion, (2) no radiographic evidence of conditions that might prevent lung reexpansion (i.e., visceral pleural entrapment or atelectasis as a result of bronchial occlusion), (3) pleural fluid cytologic studies or pleural biopsies that were positive for malignant cells, and (4) an Eastern Cooperative Oncology Group performance score of no more than 2. Exclusion criteria included (I) the inability to lie in the lateral decubitus position, (2) previously attempted ipsilateral pleurodesis, (3) a noncorrectable bleeding diathesis, (4) any change in the chemotherapy regimen within 4 weeks before the patient entered the study, and (5) radiation therapy 2 weeks before referral for pleurodesis. All patients were treated between October 1990 and February 1992 at three Indiana University Medical Center hospitals (Indiana University Hospital, Wishard Memorial County Hospital, and the Richard R. Roudebush Veterans' Administration Medical Center). Informed consent, as approved by the Indiana University Institutional Review Board, was obtained from all patients before enrollment. Technique. The thoracoscopic procedure has been described previously'? and was performed in an endoscopy suite. A largevolume thoracentesis (up to 1.5 L) was performed the day before the thoracoscopy to relieve dyspnea, estimate the potential for lung reexpansion, and minimize the risk of reexpansion pulmonary edema. Roentgenograms of the chest that included poster-
oanterior, lateral, and decubitus views were obtained to identify the optimal site of thoracoscopic entry. When indicated, a noncontrasted computed tomographic scan of the chest was obtained to further define pulmonary and pleural anatomy. Patients were placed in the lateral decubitus position with the affected hemithorax upward. Blood pressure, single-lead electrocardiograms, and cutaneous oxygen saturations were continuously monitored. Supplemental oxygen was given to maintain oxygen saturation above 90%. After sterile draping, 10 to 30 ml of 2% lidocaine solution was infiltrated into the skin and soft tissues at the level of the fourth or fifth intercostal space in the midaxillary line. Throughout the procedure, sedation was achieved with intravenous administration of midazolam (6 ± 2 mg) and either morphine sulfate (12 ± 6 mg) or meperidine (128 ± 38 mg); administration was begun before the incision and talc insufflation. For cases in which coughing was a problem, IS mg of codeine was administered intravenously. A 1.0 to 1.5 em incision was made through the skin and above the superior aspect of the rib, directly over the intercostal space to be entered. A passage to the parietal pleural was created by hemostat dissection. After confirmation of air or fluid in the pleural space by means of needle aspiration, a 10 mm trocar was inserted. An operating thoracoscope with an outer diameter of 10 mm and a working channel of either 5 mm (Wolf Medical Instruments Corp., Rosemont, lll.) or 3 mm (Storz EndoscopyAmerica, Inc., Culver City, Calif.) was inserted into the pleural space. All residual pleural fluid was aspirated under direct visualization, and the entire pleural surface was inspected. Any fibrinous adhesions that would prevent pleural surface apposition or uniform distribution of talc were lysed. Pharmaceutical-grade (USP certified), asbestos-free talc (Humco Laboratory, Texarkana, Tex.) was used as the sclerosing agent. Three-gram aliquots were heat sterilized with serial bacterial cultures to assure sterility. An average of 3 to 6 gm of talc powder was insufflated into the pleural space through a rigid suction catheter under direct vision with a pneumatic atomizer (Wolf Medical Instruments Corp.). Uniform distribution of talc on the entire pleural surface was confirmed before removal of the trocar and thoracoscope. A 28F or 32F chest tube with additional holes was inserted, preferably through a separate lower intercostal space incision, to facilitate fluid drainage. The chest tube was connected to an underwater sealed chamber with 20 em wall suction and left in place until fluid drainage was less then 100 ml per day. Control group. Eighty-five randomized patients underwent chemical sclerosis with either 60 units of bleomycin (n = 44) or 1000 mg of tetracycline (n = 41) for palliation of a malignant pleural effusion. Both drugs were diluted in 100 ml of physiologic saline solution and instilled into a tube thoracostomy after fluid drainage had diminished to less than 100 ml per day. The inclusion and exclusion criteria were identical to those for the talc-treatment group except that patients were excluded if they had received previous systemic bleomycin and there were no restrictions with respect to bleeding disorders or patient positioning. The control group was similar to the talc group with respect to gender distribution (40 men and 34 women), mean age (61 years, range 19 to 86 years), and primary tumor (Table I). Univariate statistical analysis was applied to discrete preoperative and postoperative variables (x 2 analysis, with continuity correction when appropriate) and to continuous variables (Student's t test) with Statview II software (Abacus Concepts, Ber-
The Journal of Thoracic and Cardiovascular Surgery Volume 105, Number 4
keley, Calif.) on a Macintosh II fX computer (Apple Inc, Cupertrino, Calif.),
Results Talc group. Eighteen patients died of their underlying disease before the 90-day evaluation, and six of these patients died within 30 days of the procedure, No deaths were attributable to the procedure or to recurrent effusions, All but two patients had successful pleurodesis. In both cases, extrinsic tumor compression of the right lower lobe bronchus prevented complete lobar reexpansion, which allowed reaccumulation of fluid. After 30 and 90 days, the objective success rate as determined by roentgenograms of the chest in evaluable patients was 97% and 95%, respectively, which was significantly better than in either control group (Table II). We perceived only minimal discomfort in patients during thoracoscopy and talc insufflation. We attribute this to the amnestic effects of midazolam and to parenteral narcotic analgesia. The mean duration of chest tube drainage was 4.0 ± 1.2 days, which was significantly less (p < 0.001) than the duration for those patients randomly selected for treatment with either bleomycin (mean 6.6 ± 1.6 days, n = II) or tetracycline (mean 6.5 ± 2.1 days, n = 10). The number of days of hospitalization before and after pleurodesis was dependent on factors unrelated to the sclerosis procedure; therefore, the length of hospitalization for the treatment groups was not statistically compared. Immediately after thoracoscopy and talc pleurodesis, one patient had severe chest pain;12-lead electrocardiography demonstrated diffuse, nonspecific ST-T wave changes. The patient was admitted to the intensive care unit, and a myocardial infarction was ruled out. Fever (37.5° to 39.0° C) occurred in seven patients (17%) and lasted approximately 24 hours (range 12 to 72 hours). Six patients (15%) had minor subcutaneous emphysema that required no intervention. Control group. At 30 days, 55 patients were evaluable, 28 and 27 in the bleomycin and tetracycline groups, respectively. Eighteen patients (64%) in the bleomycin group and 9 (33%) in the tetracycline group showed no evidence of pleural fluid reaccumulation (p = 0.022). After 90 days, 73 patients were evaluable; 26 of 37 patients (70%) in the bleomycin group, and 17 of 36 patients (47%) in the tetracycline group had no radiographic evidence of recurrent effusion (p = 0.045). Discussion An understanding of the various direct and indirect pathophysiologic processes that result in pleural fluid accumulation is essential in the treatment of patients with
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Table II. Success rates ofpleurodesis at 30 and 90 days after therapy Agent/technique
30 days
Talc / thoracoscopy Bleomycin/ tube Tetracycline/ tube
97% (32/33)
p Value
90 days
p Value
95% (20/21)
64% (18/28)
0.002
70% (26/37)
0.04
33% (9/27)
<0.001
47% (17/36)
<0.001
N umber of patients with successful pleurodesis expressed as a percentage and fraction (in parentheses) of the total number of evaluable patients within treatment groups. P values generated by X' versus talc.
malignant pleural effusions. Although direct invasion of the pleura is the most common mechanism, other etiologic factors may require therapeutic approaches other than pleurodesis.' Various forms oflocal therapy have been advocated for the treatment of malignant pleural effusions. Thoracentesis is valuable for relieving dyspnea. However, this has not been shown to be an effective long-term palliative measure. Anderson and associates!' report that the mean time for an effusion to recur after thoracentesis is 4.2 days and that there is a 97% recurrence rate within 30 days. Tube thoracostomy alone for the control of malignant pleural effusions has also been shown to be ineffective. 12 Another approach involves surgical placement of a pleuroperitoneal shunt.l ' However, controlled studies have yet to compare the advantages with those of chemical sclerosis. Our findings in this prospective phase II study demonstrate that the combined use of the thoracoscope for primary drainage and subsequent visual application of insufflated talc is efficacious in achieving pleurodesis for the control of malignant pleural effusions. These data are similar to those found in previous reports. 14- IS In various randomized clinical trials that compared thoracoscopically guided talc insufflation with the use of other sclerosing agents, including mustine.!" tetracycline.l'' doxycycline,'? and bleomycin.!? talc has an overall success rate that exceeds 90%. Tetracycline and bleomycin are the most commonly used sclerosing agents. Both are soluble and are therefore more easily administered through a tube thoracostomy than is talc slurry. I. 2. 9 Tetracycline has been considered to be the agent of choice in many institutions because of lower cost and availability. However, long-term success rates have been variable.s 20 and within our control group this agent was inferior to bleomycin. The variability that is found among studies is, in part, due to a lack of uniform criteria for classification of a complete response and, possibly, to suboptimal dosing (less than 1000 mg). Uneven distribution of sclerosing
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agents that are administered blindly through a thoracostomy tube, which may be surrounded by fibrinous adhesions, or rapid systemic absorption of the agent may account for many of these treatment failures. Because parenteral tetracycline is no longer available in the United States, doxycycline and minocycline are currently being investigated. The intrapleural administration of lidocaine in various doses to reduce pain after tetracycline sclerosis has been investiga ted, 4 but this technique has not met with uniform success. No such pain was reported in the talc group after the procedure. The technique of tube thoracostomy drainage until the pleural cavity is "dry" followed by chemical sclerosis has the distinct disadvantage of requiring a significantly longer hospitalization for drainage through an indwelling chest tube. This results in prolonged discomfort and prevents a more rapid return to a functional status in patients with predictably shortened life expectancies. A number of concerns regarding the use of talc, initially raised by Gaensler.i! including fear of mesothelioma and development of large pleural peels, have not been fully extrapolated.F Medical-grade talc is free of asbestos, although calcium, aluminum, and iron may be present in trace amounts. Bouchama and associates-' have described a patient who had progressive dyspnea with bilateral pulmonary infiltrates after thoracoscopic lung biopsies and talc pleurodesis. Subsequent investigation of bronchoalveolar lavage fluid revealed talc particles. Rinaldo and colleagues/" reported three cases of worsening dyspnea within 72 hours of instillation of talc slurry into a thoracostomy tube; however, large amounts oftalc (10 gm) were used. Chambers-' and later Webb and coworkers-" independently reported no such complications and excellent results with a more diluted talc slurry. Todd and associatesf when performing talc pleurodesis through an open thoracostomy, noted seven cases of respiratory failure and/or pneumonia, although the exact cause of these complications was not determined. Pulmonary complications after talc insufflation under thoracoscopic guidance have been rarely reported in the literature and may be dose-related. As the number of patients treated by this method increases, questions regarding the safety of talc insufflation may be resolved. In our series of 39 patients, we have seen no such pulmonary complications. We perform a large-volume thoracentesis before thoracoscopy, which reduces dyspnea, allows better tolerance of the procedure while the patient is under local anesthesia, and decreases the amount of fluid that needs to be removed. In addition, subsequent roentgenograms of the
The Journal of Thoracic and Cardiovascular Surgery April 1993
chest help determine whether the underlying lung is capable of full reexpansion. The two cases of recurrent effusion in this series underscore the principle that lobar bronchial compression that is caused by either extrinsic or intrinsic tumor will limit lung reexpansion and, therefore, the results of any technique to achieve pleurodesis. Similarly, an encapsulated visceral pleura may prevent reexpansion, which is usually detectable on preoperative computed tomographic scans. A severely "trapped" lung is unlikely to come into contact with the chest wall, even with compensatory mediastinal shift and diaphragmatic elevation, which is an essential requirement for successful pleurodesis. Malignant lymphangitic spread, our final contraindication to talc pleurodesis, may be the cause of perseverance of discomfort after initial therapeutic thoracentesis. No thoracoscopy had to be terminated in this series because of patient intolerance caused by pain or dyspnea. In light of excellent patient tolerance with not only thoracoscopy for talc pleurodesis but all of our diagnostic thoracoscopies that were performed with the aid of local anesthesia (95 patients at the time of this study), the routine use of general anesthesia in similar cases seems neither necessary nor cost-effective. We disagree with Hausheer and Yarbro.? who believe that thoracoscopy with local anesthesia requires a patient with low risk. We would reserve general anesthesia with controlled endotracheal ventilation for only the patient with the rare case of severe benign parenchymal disease of the lung. Although, in our institution, the majority of thoracoscopic talc pleurodesis procedures are performed by chest physicians with the aid of local anesthesia in an endoscopy suite, this procedure is easily adopted by thoracic surgeons. We realize that philosophies of credentialling differ among hospitals. We can find no reason, however, that this type of thoracoscopic procedure cannot be performed by chest physicians with appropriate training. We have developed a close working relationship between the Pulmonary Medicine and Thoracic Surgery Divisions. This collaborative effort assures that patients who undergo thoracoscopy with local anesthesia by chest physicians will not likely have to undergo further, more invasive thoracoscopic or surgical interventions under general anesthesia. Our phase II study demonstrates the safety and efficacy of thoracoscopically guided talc pleurodesis for the treatment of symptomatic malignant pleural effusions. This is a cost-effective procedure with minimal patient discomfort when performed with the aid of local anesthesia that is supplemented with intravenous sedation. In light of these preliminary data, a randomized, controlled
The Journal of Thoracic and Cardiovascular Surgery Volume 105, Number 4
clinical trial that compares standard chemical sclerosis with thoracoscopically guided talc insufflation should be considered, We thank Lawrence H. Einhorn, MD, Indiana University Division of Hematology and Oncology, and Bristol-Myers Pharmaceutical Group (Evansville, Ind.) for providing control group data. We acknowledge the technical assistance of Cherry Smith of the Indiana University Pulmonary Endoscopy Suite, REFERENCES 1. Light R W. Malignant pleural effusions. In: Light RW, ed. Pleural diseases. 2nd ed. Philadelphia: Lea & Febiger, 1990:97-115. 2. Hausheer FH, Yarbro JW. Diagnosis and treatment of malignant pleural effusion. Semin Oncol 1985;12:54-75. 3. Antony VB. Pleurodesis: testing the waters [Editorial]. Am Rev Respir Dis 1987;135:775-6. 4. Sherman S, Ravikrishnan KP, Patel AS, Seidman Jc. Optimum anesthesia with intrapleural lidocaine during chemical pleurodesis with tetracycline. Chest 1988;93: 533-7. 5. Gravelyn TR, Michelson MK, Gross BH, Sitrin RG. Tetracycline pleurodesis for malignant pleural effusions: a 10-year retrospective study. Cancer 1987;59:1973-7. 6. Todd TR, Delarue NC, Ilves R, Pearson FG, Cooper JD. Talc poudrage for malignant pleural effusion. Chest 1980; 78:542-3. 7. Haupt GJ, Camishion RC, Templeton JY, Gibbon JH. Treatment of malignant pleural effusions by talc poudrage. JAMA 1960;172:918-21. 8. Boutin C, Viallat JR, Cargnino P. Thoracoscopy. In: Chretien J, Bignon J, Hirsch A, eds. The pleura in health and disease. New York: Marcel Dekker, 1985:587-622. 9. Ruckdeschel JC, Moores DW, Lee JY, et al. Intrapleural therapy for malignant pleural effusions: a randomized comparison of bleomycin and tetracycline. Chest 1991; 100:1528-35. 10. Oldenburg FA, Newhouse MT. Thoracoscopy: a safe accurate diagnostic procedure using rigid thoracoscopy and local anesthesia. Chest 1979;75:45-50. II. Anderson CB, Philpott GW, Ferguson TB. The treatment of malignant pleural effusions. Cancer 1974;33:916-22. 12. Izbicki R, Wehing BT, Baker L, et al. Pleural effusion in cancer patients: a prospective randomized study of pleural drainage with the addition of radioactive phosphorous to the pleural space versus pleural drainage alone. Cancer 1975; 36:1511-8. 13. Tsang V, Ferando HC, Goldstraw P. Pleuroperitoneal shunt for recurrent malignant pleural effusion. Thorax 1990;45:369-72. 14. Rusch VW, Mountain C. Thoracoscopy under regional anesthesia for the diagnosis and management of pleural disease. Am J Surg 1987;154:174-8.
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15. Fentiman IS, Rubens RD, Hayward JL. A comparison of intracavitary talc and tetracycline for the control of pleural effusion secondary to breast cancer. Eur J Cancer Clin Oncol 1986;22:1079-81. 16. Aelony Y, King R, Boutin C. Thoracoscopic talc poudrage pleurodesis for chronic recurrent pleural effusions. Ann Intern Med 1991;115:778-82. 17. Hamed H, Fentimen IS, Chaudary MA, Ruben RD. Comparison of intracavitary bleomycin and talc for control of pleural effusion secondary to carcinoma of the breast. Br J Surg 1989;76:1266-7. 18. Fentiman IS, Rubens RD, Hayward JL. Control of pleural effusions in patients with breast cancer: a randomized trial. Cancer 52:1983;52:737-9. 19. Muir JF, Cerisel F, Defouilloy C, et al. Pleural drainage with talc versus doxycycline in the control of malignant pleural effusions [Abstract]. Am Rev Respir Dis 1987; I 35:A244. 20. Sherman S, Grady KJ, Seidman J'C, Clinical experience with tetracycline pleurodesis of malignant pleural effusion. South Med J 1987;80:716-9. 21. Gaensler EA. Parietal pleurectomy for recurrent spontaneous pneumothorax. Surg Gynecol Obstet 1956;102:293308. 22. Research Committee of the British Thoracic Association and the Medical Research Council Pneumoconiosis unit. A surveyoflong-term effectsof talc and kaolin pleurodesis. Br J Dis Chest 1979;73:285-8. 23. Bouchama A, Chastre J, Gaudichet A, Soler P, Gibert C. Acute pneumonitis with bilateral pleural effusion after talc pleurodesis. Chest 1984;86:795-7. 24. Rinaldo JE, Owens GR, Rogers RM. Adult respiratory distress syndrome following intrapleural instillation of talc. J THORAC CARDIOVASC SURG 1983;85:523-6. 25. Chambers JS. Palliative treatment of neoplastic pleural effusion with intercostal intubation and talc instillation. West J Surg 1958;66:26-8. 26. Webb WR, Ozmen V, Moulder PV, Shabahang B, Breaux J. Iodized talc pleurodesis for the treatment of pleural effusions. J THORAC CARDIOVASC SURG 1992;103:881-6.
Discussion Dr. Watts R. Webb (New Orleans, La.). I would like to strongly support Dr. Hartman's use of talc. We have used it in a slightly different way, instilling it into the body through the chest tube. We have used 5 gm of talc and have also added 3 gm of thymol iodide. I am not sure that this adds very much to the effectiveness,but it does give a very nice picture of the areas of lung that are completely reexpanded. The slurry, which looks like Mississippi River mud, is injected with an Asepto syringe through the tube. The tube is then clamped and the patient is turned rapidly in all directions for a couple of hours. The tube is then unclamped and left in place for an additional 4 or 5 days until the fluid is expelled and the lung is well reexpanded. In our initial series of approximately 33 patients, six were treated for benign disease and the rest for malignant disease
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along the distributions in the present study; all of them were effectively treated, both early and late. This study was presented at The Western Thoracic Surgical Association meeting last year (J THORAC CARDIOVASC SURG 1992;103:881-6). Since that time we have treated an additional 12 patients with one failure. I think this occurred because we removed the tube much too quickly; the patient was very eager to return to her home in a different city and we acquiesced. Unfortunately, she had a recurrence. We would suggest also that you do not hesitate to put in two or more tubes if needed because it is essential to get all the fluid out during the postoperative period. We have had no further complications, and chest pain has been a minimal problem. We believe that the result of this has been another nail, as Dr. Hartman's group has shown, in the coffin of bleomycin and tetracycline for pleurodesis. Dr. Darroch W. O. Moores (Albany, N.Y). I think that the only agent more effective than talc in causing pleurodesis is pus. The Toronto Group have a long experience with talc, and it works very well. The problem with talc in the United States is its relative lack of availability. Asbestos-free talcum powder is readily available, but not in a sterile form. It must be sterilized bydry heat or gamma radiation. Obtaining institutional approval for the use of talc can be a rigorous process that involvesmultiple committees. Currently, for the majority of patients in the United States, talcum powder is not available. It will require much work by the members of this Association to get talcum powder made available at their respective hospitals. In the meantime, bleomycin is available, it works approximately 70% of the time, and it is a reasonable alternative until talc becomes more readily available. Dr. John S. Chambers (San Diego, Calif). This is an important paper because it backs up all the work I know of that states that talc is better than any other sclerosant. Talc has been available in San Diego for 40 years; in fact, I have used it for 40 years. I even published a paper on my first 30 cases in 1958. It works. Talc works regardless of the method in which it enters the pleural cavity, whether you put it in with a teaspoon during the surgical procedure, whether you put it in as a powder with a blower, or whether you put it in through tubes as a slurry. I have used the slurry, and if I had my choice I would make the politically incorrect statement and say that talc should first be tried as a slurry because it is so much easier to use that way. It was a little difficult to get the hospitals to sterilize talc and (USP asbestos-free) put it up as a slurry. In San Diego, several hospitals now do this by heat sterilization and then put 5 to 15
The Journal of Thoracic and Cardiovascular Surgery April 1993
gm in a 250 ml bottle with 100 ml of saline solution; they shake it up and there it is, a slurry that can be used all over the hospital or all over town. It is available and used in the United States as well as in Canada. Dr. William A. Cook (North Andover, Mass.). If you add the cost of the thoracoscopy procedure to the instillation of the talc, then you are going to come very close to the cost of the bleomycin. Thus one good reason to instill talc by a slurry technique is that it is infinitely cheaper. Dr. L. Penfield Faber (Chicago, Ill.). In your described technique, you alluded to a large-volume thoracentesis. Rapid and complete removal of a large amount of pleural effusion can precipitate unilateral pulmonary edema. It is our practice to clamp the chest tube after 500 ml has been removed and then slowly evacuate the remainder of the pleural effusion at appropriate intervals (as I have had personal experience with unilateral pulmonary edema after rapid evacuation of a large-volume pleural effusion). When you carry out the thoracentesis, are you concerned about unilateral pulmonary edema, and, if so, what cautionary measures do you take in this regard? Dr. Hartman Starting with Dr. Webb, we use thoracoscopy to apply talc but also to remove all residual fluid. This shortens the duration of chest tube drainage. We perform a large-volume thoracocentesis of up to 1.5 L the day before the procedure. This improves dyspnea and helps in the evaluation of lung reexpansion. We are concerned about reexpansion pulmonary edema; however, when fluid is removed in two stages, we have no complications. I agree with him that removing the tube too quickly can result in some failures and may have been responsible for failure in our control group. We use not two chest tubes but one, which is placed as low in the hemithorax as possible and posteriorly with additional holes. I appreciate the comments of Dr. Moore, who was involved with the control group. With regard to the lack of availability of talc, this will become more available. At our institution we heat sterilize talc and have serially cultured it to ensure sterility. The cost of bleomycin, in Indianapolis, is $750 for 60 units. With regard to Dr. Chambers, we appreciate his experience in using talc slurry for more than 40 years. With regard to Dr. Cook, thoracoscopically guided talc insufflation is cost-effective. When the cost of thoracoscopy is added to the 10 cents per application of talc, this comes out to approximately the cost of bleomycin, and you decrease days of hospitalization and prevent recurrences.
Daniel L. Hartman, MDa (by invitation), James M. Gaither, MDa (by invitation), Kenneth A. Kesler, MD b (by invitation), Deborah M. Mylet, RNa (by invitation), John W. Brown, MD,b and Praveen N. Mathur, MB, BSa (by invitation), Indianapolis, Ind.
Symptomatic malignant pleural effusions are caused by a variety of frequently incurable tumors that involve the pleural surfaces. As many as 50% of patients with breast and lung cancer will have a pleural effusion during the course of their disease. I Numerous methods/ have been advocated to induce pleurodesis, but no therapy has been consistently demonstrated to be superior.
From the Divisions of Pulmonary and Critical Care," Department of Medicine, and Cardiothoracic Surgery," Department of Surgery, Indiana University School of Medicine, Indianapolis, Ind. Read at the Seventy-second Annual Meeting of the American Association for Thoracic Surgery, Los Angeles, Calif., April 26-29, 1992. Address for reprints: Praveen N. Mathur, MB, BS, Division of Pulmonary and Critical Care, Department of Medicine, WOP 439 C, 100I West 10th St., Indianapolis, IN 46202. Copyright
1993 by Mosby-Year Book, Inc.
0022-5223/93 $1.00
+ .10
12/6/43347
In North America, the most widely accepted treatment of malignant pleural effusions includes initial tube thoracostomy drainage for a variable period of time, followed by instillation of tetracycline to achieve a chemical pleurodesis.l-:' This form of therapy, however, has a significant prevalence of morbidity, which includes pain 1,4 and, not infrequently, treatment failures that require additional therapy' Talc has been applied directly to the pleural surfaces after open thoracotomy'-? to achieve successful pleurodesis. However, this technique has never become popular because a prolonged recovery is necessary in patients with limited life expectancies. Boutin, Viallat, and Cargnino" have demonstrated that insufflated talc may be introduced into the pleural space by modern thoracoscopic techniques with minimal morbidity. We performed this study to evaluate talc insufflation under thoracoscopic guidance as a potentially more effective treatment of symptomatic malignant pleural effusions with a lower morbidity rate. 743
744
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Hartman et al.
Table I. Primary malignancy sites in evaluable patients Primary site Lung
Breast Ovary Other
talc
Bleomycin
Tetracycline
13 (39%) 8 (24%) 4 (12%) 8 (24%)
13 (36%) 9 (24%) 1(3%) 15 (39%)
13 (36%) 10 (28%) 2 (6%) II (31%)
Number of patients per site and percentage of treatment group (in parentheses). There was no significant statistical difference between the treatment groups (p = 0.63).
Patients and methods Study design. This was a prospective phase II open-label study that evaluated talc insufflation under thoracoscopic guidance as compared with documented controls." This control group consisted of patients who participated in a multicenter randomized study, which involved our institution and which evaluated tube thoracostomy drainage that was followed by either bleomycin or tetracycline chemical sclerosis. Successful pleurodesis was defined in all treatment groups as showing no reaccumulation of pleural fluid as determined by serial roentgenograms of the chest compared with roentgenograms before removal of the tube thoracostomy. Pleurodesis was considered unsuccessful if chest roentgenograms confirmed reaccumulation of pleural fluid. Follow-up visits that included roentgenograms of the chest were made at 30 and 90 days. Talc group. We performed thoracoscopic talc pleurodesis in 39 patients (20 men and 19 women), whose ages ranged from 41 to 88 years (mean, 58.8), with malignant pleural effusions as a result of a variety of primary malignant tumors (Table I). Patients were included in this prospective study if they met the following criteria: (I) dyspnea that improved after large-volume thoracentesis with subsequent recurrence of a symptomatic pleural effusion, (2) no radiographic evidence of conditions that might prevent lung reexpansion (i.e., visceral pleural entrapment or atelectasis as a result of bronchial occlusion), (3) pleural fluid cytologic studies or pleural biopsies that were positive for malignant cells, and (4) an Eastern Cooperative Oncology Group performance score of no more than 2. Exclusion criteria included (I) the inability to lie in the lateral decubitus position, (2) previously attempted ipsilateral pleurodesis, (3) a noncorrectable bleeding diathesis, (4) any change in the chemotherapy regimen within 4 weeks before the patient entered the study, and (5) radiation therapy 2 weeks before referral for pleurodesis. All patients were treated between October 1990 and February 1992 at three Indiana University Medical Center hospitals (Indiana University Hospital, Wishard Memorial County Hospital, and the Richard R. Roudebush Veterans' Administration Medical Center). Informed consent, as approved by the Indiana University Institutional Review Board, was obtained from all patients before enrollment. Technique. The thoracoscopic procedure has been described previously'? and was performed in an endoscopy suite. A largevolume thoracentesis (up to 1.5 L) was performed the day before the thoracoscopy to relieve dyspnea, estimate the potential for lung reexpansion, and minimize the risk of reexpansion pulmonary edema. Roentgenograms of the chest that included poster-
oanterior, lateral, and decubitus views were obtained to identify the optimal site of thoracoscopic entry. When indicated, a noncontrasted computed tomographic scan of the chest was obtained to further define pulmonary and pleural anatomy. Patients were placed in the lateral decubitus position with the affected hemithorax upward. Blood pressure, single-lead electrocardiograms, and cutaneous oxygen saturations were continuously monitored. Supplemental oxygen was given to maintain oxygen saturation above 90%. After sterile draping, 10 to 30 ml of 2% lidocaine solution was infiltrated into the skin and soft tissues at the level of the fourth or fifth intercostal space in the midaxillary line. Throughout the procedure, sedation was achieved with intravenous administration of midazolam (6 ± 2 mg) and either morphine sulfate (12 ± 6 mg) or meperidine (128 ± 38 mg); administration was begun before the incision and talc insufflation. For cases in which coughing was a problem, IS mg of codeine was administered intravenously. A 1.0 to 1.5 em incision was made through the skin and above the superior aspect of the rib, directly over the intercostal space to be entered. A passage to the parietal pleural was created by hemostat dissection. After confirmation of air or fluid in the pleural space by means of needle aspiration, a 10 mm trocar was inserted. An operating thoracoscope with an outer diameter of 10 mm and a working channel of either 5 mm (Wolf Medical Instruments Corp., Rosemont, lll.) or 3 mm (Storz EndoscopyAmerica, Inc., Culver City, Calif.) was inserted into the pleural space. All residual pleural fluid was aspirated under direct visualization, and the entire pleural surface was inspected. Any fibrinous adhesions that would prevent pleural surface apposition or uniform distribution of talc were lysed. Pharmaceutical-grade (USP certified), asbestos-free talc (Humco Laboratory, Texarkana, Tex.) was used as the sclerosing agent. Three-gram aliquots were heat sterilized with serial bacterial cultures to assure sterility. An average of 3 to 6 gm of talc powder was insufflated into the pleural space through a rigid suction catheter under direct vision with a pneumatic atomizer (Wolf Medical Instruments Corp.). Uniform distribution of talc on the entire pleural surface was confirmed before removal of the trocar and thoracoscope. A 28F or 32F chest tube with additional holes was inserted, preferably through a separate lower intercostal space incision, to facilitate fluid drainage. The chest tube was connected to an underwater sealed chamber with 20 em wall suction and left in place until fluid drainage was less then 100 ml per day. Control group. Eighty-five randomized patients underwent chemical sclerosis with either 60 units of bleomycin (n = 44) or 1000 mg of tetracycline (n = 41) for palliation of a malignant pleural effusion. Both drugs were diluted in 100 ml of physiologic saline solution and instilled into a tube thoracostomy after fluid drainage had diminished to less than 100 ml per day. The inclusion and exclusion criteria were identical to those for the talc-treatment group except that patients were excluded if they had received previous systemic bleomycin and there were no restrictions with respect to bleeding disorders or patient positioning. The control group was similar to the talc group with respect to gender distribution (40 men and 34 women), mean age (61 years, range 19 to 86 years), and primary tumor (Table I). Univariate statistical analysis was applied to discrete preoperative and postoperative variables (x 2 analysis, with continuity correction when appropriate) and to continuous variables (Student's t test) with Statview II software (Abacus Concepts, Ber-
The Journal of Thoracic and Cardiovascular Surgery Volume 105, Number 4
keley, Calif.) on a Macintosh II fX computer (Apple Inc, Cupertrino, Calif.),
Results Talc group. Eighteen patients died of their underlying disease before the 90-day evaluation, and six of these patients died within 30 days of the procedure, No deaths were attributable to the procedure or to recurrent effusions, All but two patients had successful pleurodesis. In both cases, extrinsic tumor compression of the right lower lobe bronchus prevented complete lobar reexpansion, which allowed reaccumulation of fluid. After 30 and 90 days, the objective success rate as determined by roentgenograms of the chest in evaluable patients was 97% and 95%, respectively, which was significantly better than in either control group (Table II). We perceived only minimal discomfort in patients during thoracoscopy and talc insufflation. We attribute this to the amnestic effects of midazolam and to parenteral narcotic analgesia. The mean duration of chest tube drainage was 4.0 ± 1.2 days, which was significantly less (p < 0.001) than the duration for those patients randomly selected for treatment with either bleomycin (mean 6.6 ± 1.6 days, n = II) or tetracycline (mean 6.5 ± 2.1 days, n = 10). The number of days of hospitalization before and after pleurodesis was dependent on factors unrelated to the sclerosis procedure; therefore, the length of hospitalization for the treatment groups was not statistically compared. Immediately after thoracoscopy and talc pleurodesis, one patient had severe chest pain;12-lead electrocardiography demonstrated diffuse, nonspecific ST-T wave changes. The patient was admitted to the intensive care unit, and a myocardial infarction was ruled out. Fever (37.5° to 39.0° C) occurred in seven patients (17%) and lasted approximately 24 hours (range 12 to 72 hours). Six patients (15%) had minor subcutaneous emphysema that required no intervention. Control group. At 30 days, 55 patients were evaluable, 28 and 27 in the bleomycin and tetracycline groups, respectively. Eighteen patients (64%) in the bleomycin group and 9 (33%) in the tetracycline group showed no evidence of pleural fluid reaccumulation (p = 0.022). After 90 days, 73 patients were evaluable; 26 of 37 patients (70%) in the bleomycin group, and 17 of 36 patients (47%) in the tetracycline group had no radiographic evidence of recurrent effusion (p = 0.045). Discussion An understanding of the various direct and indirect pathophysiologic processes that result in pleural fluid accumulation is essential in the treatment of patients with
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Table II. Success rates ofpleurodesis at 30 and 90 days after therapy Agent/technique
30 days
Talc / thoracoscopy Bleomycin/ tube Tetracycline/ tube
97% (32/33)
p Value
90 days
p Value
95% (20/21)
64% (18/28)
0.002
70% (26/37)
0.04
33% (9/27)
<0.001
47% (17/36)
<0.001
N umber of patients with successful pleurodesis expressed as a percentage and fraction (in parentheses) of the total number of evaluable patients within treatment groups. P values generated by X' versus talc.
malignant pleural effusions. Although direct invasion of the pleura is the most common mechanism, other etiologic factors may require therapeutic approaches other than pleurodesis.' Various forms oflocal therapy have been advocated for the treatment of malignant pleural effusions. Thoracentesis is valuable for relieving dyspnea. However, this has not been shown to be an effective long-term palliative measure. Anderson and associates!' report that the mean time for an effusion to recur after thoracentesis is 4.2 days and that there is a 97% recurrence rate within 30 days. Tube thoracostomy alone for the control of malignant pleural effusions has also been shown to be ineffective. 12 Another approach involves surgical placement of a pleuroperitoneal shunt.l ' However, controlled studies have yet to compare the advantages with those of chemical sclerosis. Our findings in this prospective phase II study demonstrate that the combined use of the thoracoscope for primary drainage and subsequent visual application of insufflated talc is efficacious in achieving pleurodesis for the control of malignant pleural effusions. These data are similar to those found in previous reports. 14- IS In various randomized clinical trials that compared thoracoscopically guided talc insufflation with the use of other sclerosing agents, including mustine.!" tetracycline.l'' doxycycline,'? and bleomycin.!? talc has an overall success rate that exceeds 90%. Tetracycline and bleomycin are the most commonly used sclerosing agents. Both are soluble and are therefore more easily administered through a tube thoracostomy than is talc slurry. I. 2. 9 Tetracycline has been considered to be the agent of choice in many institutions because of lower cost and availability. However, long-term success rates have been variable.s 20 and within our control group this agent was inferior to bleomycin. The variability that is found among studies is, in part, due to a lack of uniform criteria for classification of a complete response and, possibly, to suboptimal dosing (less than 1000 mg). Uneven distribution of sclerosing
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agents that are administered blindly through a thoracostomy tube, which may be surrounded by fibrinous adhesions, or rapid systemic absorption of the agent may account for many of these treatment failures. Because parenteral tetracycline is no longer available in the United States, doxycycline and minocycline are currently being investigated. The intrapleural administration of lidocaine in various doses to reduce pain after tetracycline sclerosis has been investiga ted, 4 but this technique has not met with uniform success. No such pain was reported in the talc group after the procedure. The technique of tube thoracostomy drainage until the pleural cavity is "dry" followed by chemical sclerosis has the distinct disadvantage of requiring a significantly longer hospitalization for drainage through an indwelling chest tube. This results in prolonged discomfort and prevents a more rapid return to a functional status in patients with predictably shortened life expectancies. A number of concerns regarding the use of talc, initially raised by Gaensler.i! including fear of mesothelioma and development of large pleural peels, have not been fully extrapolated.F Medical-grade talc is free of asbestos, although calcium, aluminum, and iron may be present in trace amounts. Bouchama and associates-' have described a patient who had progressive dyspnea with bilateral pulmonary infiltrates after thoracoscopic lung biopsies and talc pleurodesis. Subsequent investigation of bronchoalveolar lavage fluid revealed talc particles. Rinaldo and colleagues/" reported three cases of worsening dyspnea within 72 hours of instillation of talc slurry into a thoracostomy tube; however, large amounts oftalc (10 gm) were used. Chambers-' and later Webb and coworkers-" independently reported no such complications and excellent results with a more diluted talc slurry. Todd and associatesf when performing talc pleurodesis through an open thoracostomy, noted seven cases of respiratory failure and/or pneumonia, although the exact cause of these complications was not determined. Pulmonary complications after talc insufflation under thoracoscopic guidance have been rarely reported in the literature and may be dose-related. As the number of patients treated by this method increases, questions regarding the safety of talc insufflation may be resolved. In our series of 39 patients, we have seen no such pulmonary complications. We perform a large-volume thoracentesis before thoracoscopy, which reduces dyspnea, allows better tolerance of the procedure while the patient is under local anesthesia, and decreases the amount of fluid that needs to be removed. In addition, subsequent roentgenograms of the
The Journal of Thoracic and Cardiovascular Surgery April 1993
chest help determine whether the underlying lung is capable of full reexpansion. The two cases of recurrent effusion in this series underscore the principle that lobar bronchial compression that is caused by either extrinsic or intrinsic tumor will limit lung reexpansion and, therefore, the results of any technique to achieve pleurodesis. Similarly, an encapsulated visceral pleura may prevent reexpansion, which is usually detectable on preoperative computed tomographic scans. A severely "trapped" lung is unlikely to come into contact with the chest wall, even with compensatory mediastinal shift and diaphragmatic elevation, which is an essential requirement for successful pleurodesis. Malignant lymphangitic spread, our final contraindication to talc pleurodesis, may be the cause of perseverance of discomfort after initial therapeutic thoracentesis. No thoracoscopy had to be terminated in this series because of patient intolerance caused by pain or dyspnea. In light of excellent patient tolerance with not only thoracoscopy for talc pleurodesis but all of our diagnostic thoracoscopies that were performed with the aid of local anesthesia (95 patients at the time of this study), the routine use of general anesthesia in similar cases seems neither necessary nor cost-effective. We disagree with Hausheer and Yarbro.? who believe that thoracoscopy with local anesthesia requires a patient with low risk. We would reserve general anesthesia with controlled endotracheal ventilation for only the patient with the rare case of severe benign parenchymal disease of the lung. Although, in our institution, the majority of thoracoscopic talc pleurodesis procedures are performed by chest physicians with the aid of local anesthesia in an endoscopy suite, this procedure is easily adopted by thoracic surgeons. We realize that philosophies of credentialling differ among hospitals. We can find no reason, however, that this type of thoracoscopic procedure cannot be performed by chest physicians with appropriate training. We have developed a close working relationship between the Pulmonary Medicine and Thoracic Surgery Divisions. This collaborative effort assures that patients who undergo thoracoscopy with local anesthesia by chest physicians will not likely have to undergo further, more invasive thoracoscopic or surgical interventions under general anesthesia. Our phase II study demonstrates the safety and efficacy of thoracoscopically guided talc pleurodesis for the treatment of symptomatic malignant pleural effusions. This is a cost-effective procedure with minimal patient discomfort when performed with the aid of local anesthesia that is supplemented with intravenous sedation. In light of these preliminary data, a randomized, controlled
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clinical trial that compares standard chemical sclerosis with thoracoscopically guided talc insufflation should be considered, We thank Lawrence H. Einhorn, MD, Indiana University Division of Hematology and Oncology, and Bristol-Myers Pharmaceutical Group (Evansville, Ind.) for providing control group data. We acknowledge the technical assistance of Cherry Smith of the Indiana University Pulmonary Endoscopy Suite, REFERENCES 1. Light R W. Malignant pleural effusions. In: Light RW, ed. Pleural diseases. 2nd ed. Philadelphia: Lea & Febiger, 1990:97-115. 2. Hausheer FH, Yarbro JW. Diagnosis and treatment of malignant pleural effusion. Semin Oncol 1985;12:54-75. 3. Antony VB. Pleurodesis: testing the waters [Editorial]. Am Rev Respir Dis 1987;135:775-6. 4. Sherman S, Ravikrishnan KP, Patel AS, Seidman Jc. Optimum anesthesia with intrapleural lidocaine during chemical pleurodesis with tetracycline. Chest 1988;93: 533-7. 5. Gravelyn TR, Michelson MK, Gross BH, Sitrin RG. Tetracycline pleurodesis for malignant pleural effusions: a 10-year retrospective study. Cancer 1987;59:1973-7. 6. Todd TR, Delarue NC, Ilves R, Pearson FG, Cooper JD. Talc poudrage for malignant pleural effusion. Chest 1980; 78:542-3. 7. Haupt GJ, Camishion RC, Templeton JY, Gibbon JH. Treatment of malignant pleural effusions by talc poudrage. JAMA 1960;172:918-21. 8. Boutin C, Viallat JR, Cargnino P. Thoracoscopy. In: Chretien J, Bignon J, Hirsch A, eds. The pleura in health and disease. New York: Marcel Dekker, 1985:587-622. 9. Ruckdeschel JC, Moores DW, Lee JY, et al. Intrapleural therapy for malignant pleural effusions: a randomized comparison of bleomycin and tetracycline. Chest 1991; 100:1528-35. 10. Oldenburg FA, Newhouse MT. Thoracoscopy: a safe accurate diagnostic procedure using rigid thoracoscopy and local anesthesia. Chest 1979;75:45-50. II. Anderson CB, Philpott GW, Ferguson TB. The treatment of malignant pleural effusions. Cancer 1974;33:916-22. 12. Izbicki R, Wehing BT, Baker L, et al. Pleural effusion in cancer patients: a prospective randomized study of pleural drainage with the addition of radioactive phosphorous to the pleural space versus pleural drainage alone. Cancer 1975; 36:1511-8. 13. Tsang V, Ferando HC, Goldstraw P. Pleuroperitoneal shunt for recurrent malignant pleural effusion. Thorax 1990;45:369-72. 14. Rusch VW, Mountain C. Thoracoscopy under regional anesthesia for the diagnosis and management of pleural disease. Am J Surg 1987;154:174-8.
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15. Fentiman IS, Rubens RD, Hayward JL. A comparison of intracavitary talc and tetracycline for the control of pleural effusion secondary to breast cancer. Eur J Cancer Clin Oncol 1986;22:1079-81. 16. Aelony Y, King R, Boutin C. Thoracoscopic talc poudrage pleurodesis for chronic recurrent pleural effusions. Ann Intern Med 1991;115:778-82. 17. Hamed H, Fentimen IS, Chaudary MA, Ruben RD. Comparison of intracavitary bleomycin and talc for control of pleural effusion secondary to carcinoma of the breast. Br J Surg 1989;76:1266-7. 18. Fentiman IS, Rubens RD, Hayward JL. Control of pleural effusions in patients with breast cancer: a randomized trial. Cancer 52:1983;52:737-9. 19. Muir JF, Cerisel F, Defouilloy C, et al. Pleural drainage with talc versus doxycycline in the control of malignant pleural effusions [Abstract]. Am Rev Respir Dis 1987; I 35:A244. 20. Sherman S, Grady KJ, Seidman J'C, Clinical experience with tetracycline pleurodesis of malignant pleural effusion. South Med J 1987;80:716-9. 21. Gaensler EA. Parietal pleurectomy for recurrent spontaneous pneumothorax. Surg Gynecol Obstet 1956;102:293308. 22. Research Committee of the British Thoracic Association and the Medical Research Council Pneumoconiosis unit. A surveyoflong-term effectsof talc and kaolin pleurodesis. Br J Dis Chest 1979;73:285-8. 23. Bouchama A, Chastre J, Gaudichet A, Soler P, Gibert C. Acute pneumonitis with bilateral pleural effusion after talc pleurodesis. Chest 1984;86:795-7. 24. Rinaldo JE, Owens GR, Rogers RM. Adult respiratory distress syndrome following intrapleural instillation of talc. J THORAC CARDIOVASC SURG 1983;85:523-6. 25. Chambers JS. Palliative treatment of neoplastic pleural effusion with intercostal intubation and talc instillation. West J Surg 1958;66:26-8. 26. Webb WR, Ozmen V, Moulder PV, Shabahang B, Breaux J. Iodized talc pleurodesis for the treatment of pleural effusions. J THORAC CARDIOVASC SURG 1992;103:881-6.
Discussion Dr. Watts R. Webb (New Orleans, La.). I would like to strongly support Dr. Hartman's use of talc. We have used it in a slightly different way, instilling it into the body through the chest tube. We have used 5 gm of talc and have also added 3 gm of thymol iodide. I am not sure that this adds very much to the effectiveness,but it does give a very nice picture of the areas of lung that are completely reexpanded. The slurry, which looks like Mississippi River mud, is injected with an Asepto syringe through the tube. The tube is then clamped and the patient is turned rapidly in all directions for a couple of hours. The tube is then unclamped and left in place for an additional 4 or 5 days until the fluid is expelled and the lung is well reexpanded. In our initial series of approximately 33 patients, six were treated for benign disease and the rest for malignant disease
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along the distributions in the present study; all of them were effectively treated, both early and late. This study was presented at The Western Thoracic Surgical Association meeting last year (J THORAC CARDIOVASC SURG 1992;103:881-6). Since that time we have treated an additional 12 patients with one failure. I think this occurred because we removed the tube much too quickly; the patient was very eager to return to her home in a different city and we acquiesced. Unfortunately, she had a recurrence. We would suggest also that you do not hesitate to put in two or more tubes if needed because it is essential to get all the fluid out during the postoperative period. We have had no further complications, and chest pain has been a minimal problem. We believe that the result of this has been another nail, as Dr. Hartman's group has shown, in the coffin of bleomycin and tetracycline for pleurodesis. Dr. Darroch W. O. Moores (Albany, N.Y). I think that the only agent more effective than talc in causing pleurodesis is pus. The Toronto Group have a long experience with talc, and it works very well. The problem with talc in the United States is its relative lack of availability. Asbestos-free talcum powder is readily available, but not in a sterile form. It must be sterilized bydry heat or gamma radiation. Obtaining institutional approval for the use of talc can be a rigorous process that involvesmultiple committees. Currently, for the majority of patients in the United States, talcum powder is not available. It will require much work by the members of this Association to get talcum powder made available at their respective hospitals. In the meantime, bleomycin is available, it works approximately 70% of the time, and it is a reasonable alternative until talc becomes more readily available. Dr. John S. Chambers (San Diego, Calif). This is an important paper because it backs up all the work I know of that states that talc is better than any other sclerosant. Talc has been available in San Diego for 40 years; in fact, I have used it for 40 years. I even published a paper on my first 30 cases in 1958. It works. Talc works regardless of the method in which it enters the pleural cavity, whether you put it in with a teaspoon during the surgical procedure, whether you put it in as a powder with a blower, or whether you put it in through tubes as a slurry. I have used the slurry, and if I had my choice I would make the politically incorrect statement and say that talc should first be tried as a slurry because it is so much easier to use that way. It was a little difficult to get the hospitals to sterilize talc and (USP asbestos-free) put it up as a slurry. In San Diego, several hospitals now do this by heat sterilization and then put 5 to 15
The Journal of Thoracic and Cardiovascular Surgery April 1993
gm in a 250 ml bottle with 100 ml of saline solution; they shake it up and there it is, a slurry that can be used all over the hospital or all over town. It is available and used in the United States as well as in Canada. Dr. William A. Cook (North Andover, Mass.). If you add the cost of the thoracoscopy procedure to the instillation of the talc, then you are going to come very close to the cost of the bleomycin. Thus one good reason to instill talc by a slurry technique is that it is infinitely cheaper. Dr. L. Penfield Faber (Chicago, Ill.). In your described technique, you alluded to a large-volume thoracentesis. Rapid and complete removal of a large amount of pleural effusion can precipitate unilateral pulmonary edema. It is our practice to clamp the chest tube after 500 ml has been removed and then slowly evacuate the remainder of the pleural effusion at appropriate intervals (as I have had personal experience with unilateral pulmonary edema after rapid evacuation of a large-volume pleural effusion). When you carry out the thoracentesis, are you concerned about unilateral pulmonary edema, and, if so, what cautionary measures do you take in this regard? Dr. Hartman Starting with Dr. Webb, we use thoracoscopy to apply talc but also to remove all residual fluid. This shortens the duration of chest tube drainage. We perform a large-volume thoracocentesis of up to 1.5 L the day before the procedure. This improves dyspnea and helps in the evaluation of lung reexpansion. We are concerned about reexpansion pulmonary edema; however, when fluid is removed in two stages, we have no complications. I agree with him that removing the tube too quickly can result in some failures and may have been responsible for failure in our control group. We use not two chest tubes but one, which is placed as low in the hemithorax as possible and posteriorly with additional holes. I appreciate the comments of Dr. Moore, who was involved with the control group. With regard to the lack of availability of talc, this will become more available. At our institution we heat sterilize talc and have serially cultured it to ensure sterility. The cost of bleomycin, in Indianapolis, is $750 for 60 units. With regard to Dr. Chambers, we appreciate his experience in using talc slurry for more than 40 years. With regard to Dr. Cook, thoracoscopically guided talc insufflation is cost-effective. When the cost of thoracoscopy is added to the 10 cents per application of talc, this comes out to approximately the cost of bleomycin, and you decrease days of hospitalization and prevent recurrences.