Talc Should Be Used for Pleurodesis

Steven A. Sahn

Division of Pulmonary and Critical Care Medicine, Allergy and Clinical Immunology, Medical University of South Carolina, Charleston, South Carolina

	PLEURODESIS

TOP PLEURODESIS MECHANISMS OF TALC PLEURODESIS CONCLUSION REFERENCES

Dyspnea is the major symptom that distresses patients with malignant pleural effusions. Patients with recurrent, symptomatic malignant pleural effusions require local therapy for relief of breathlessness, unless they have a tumor cell type that is sensitive to chemotherapy. Chemical pleurodesis, the preferred form of local therapy, has been used with variable success for decades. The difference in success rates can be explained by the effectiveness of the various pleurodesis agents used, patient selection, procedural technique, dosage, and various success criteria. However, comprehensive literature reviews (1, 2), uncontrolled case series (3, 4), and head-to-head comparisons (5) have shown that talc, whether by poudrage or slurry, is the most effective pleurodesis agent available.

	MECHANISMS OF TALC PLEURODESIS

TOP PLEURODESIS MECHANISMS OF TALC PLEURODESIS CONCLUSION REFERENCES

After talc has contacted the metabolically active mesothelial cell, an interleukin 8 (IL-8)-mediated neutrophil influx into the pleural space occurs and is subsequently followed by macrophage accumulation (6). Talc-stimulated macrophages also release IL-8, in addition to macrophage chemoattractant protein 1 (MCP-1), and in the presence of adhesion molecule expression on the mesothelial cell may amplify the inflammatory response (7). In successful talc pleurodesis, pleural fibrinolytic activity declines, suggesting an important role of the coagulation cascade. Finally, talc instillation is associated with a rapid and marked rise in basic fibroblast growth factor (bFGF) in pleural fluid that is derived from mesothelial cells (8). When there is extensive tumor covering the mesothelium, pleurodesis is less effective, further supporting the key role of the mesothelial cell in pleural fibrosis.

The Ideal Pleurodesis Agent

The ideal chemotherapeutic agent, whether it be a chemical for pleurodesis or an antibiotic for infection, should be highly effective, easy to administer, inexpensive, virtually free of adverse effects, and not associated with serious adverse events. Talc fits these criteria.

Effectiveness

A review of the English literature from 1966 to 1994 of 1,168 patients treated with chemical agents for malignant pleural effusions showed that talc was clearly the most effective, with a complete success rate of 93%, compared with Corynebacterium parvum (76%, no longer available), tetracycline (67%, no longer available), doxycycline (72%, usually requiring multiple doses), and bleomycin (54%, costly) (1). Furthermore, in 32 case series of 723 patients of predominantly malignant effusions, talc was effective either completely or partially in 659 (91%) of cases (2).

Cost

Asbestos-free talc can be ordered from chemical supply companies worldwide. Talc is inexpensive, costing approximately $0.30 for a 5-g dose compared with $86.00 for 500 mg of doxycycline and $1,140.00 for 70 units of bleomycin (1). Although talc is not packaged sterilely by the manufacturer, limitation on the number of microorganisms is a part of USP specifications; and total bacteria count cannot exceed 500/g. Only Bacillus sp., an aerobic, spore-forming, gram-positive rod, was cultured from talc received from six chemical supply companies in the United States (9). Heat sterilization (132° C for 6 h), ethylene oxide gas sterilization (130° C for 1.75 h), and  irradiation (9.4 h) were all effective sterilization techniques, with dry heat being the least expensive ($4.74 for 5 g). After sterilization, talc remained bacteria free for at least 1 yr. Talc can be least costly if applied as a slurry through a 24- to 28F standard chest tube or a 12- to 14F pigtail catheter (10). Patients usually can be discharged from hospital within 72 h if the procedure is performed expeditiously, with instillation of talc immediately after complete radiographic lung expansion even if the drainage volume exceeds 150 ml/24 h. Talc slurry pleurodesis can be accomplished on an outpatient basis (11). Talc poudrage via thoracoscopy has been shown to be no more effective than talc slurry in the treatment of malignant effusions (2, 12) and encumbers the added expense of thoracoscopy, which can be minimized if performed under conscious sedation in an endoscopy suite rather than in the operating room.

Acute Minor Adverse Effects

Chest pain and fever are the most common adverse effects of all pleurodesis agents (1). The intensity of chest pain reported with talc has ranged from nonexistent to severe but, generally, has been minimal with an incidence of 7% (9 of 131 patients) (1). Chest pain with bleomycin (56 of 199, 28%) and doxycycline (24 of 60, 40%) typically is more severe (1). The Department of Veterans Affairs cooperative study of prevention of recurrent spontaneous pneumothorax with tetracycline was almost discontinued because of severe chest pain (13). The use, dosage, and type of pre- and postpleurodesis pain medication is not clearly delineated in the literature and, therefore, makes assessment of pain problematic. Talc causes fever (usually < 38° C) in 16-69% of cases (1, 2), characteristically occurring 4 to 12 h after instillation and lasting no longer than 72 h.

Acute Serious Adverse Effects

Serious adverse effects that have rarely been reported with talc include empyema, arrythmia, and respiratory failure (2). If sterile talc is instilled, the incidence of empyema should approach zero as long as aseptic technique is employed. Since patients with recurrent malignant effusions often have comorbid diseases, it is not surprising that chest tube insertion and instillation of any pleurodesis agent could precipitate a propensity for supraventricular arrhythmias.

The one niggling issue, which has received much attention in the United States recently and has prevented talc from being universally accepted as the ideal pleurodesis agent, has been the temporal association of cases of acute respiratory failure with talc poudrage or slurry (14). In a review of 30, mostly retrospective, published case series of 9 to 360 patients from 1958 to 1999, I found that acute respiratory failure (within 48 h of instillation) occurred in 17 (0.71%) of 2,393 patients who received talc slurry or poudrage for treatment of recurrent, symptomatic pleural effusions (mostly malignant). In 12 case series (14 to 356 patients) totaling 659 patients treated with talc poudrage for pneumothorax, 1 (0.15%) patient with respiratory failure was reported (2). However, the true number of patients receiving talc pleurodesis and the associated cases of acute respiratory failure are unknown. In three case reports, five patients receiving talc pleurodesis were reported with acute respiratory failure (18). Respiratory failure is associated with talc pleurodesis; however, causation is uncertain. There are multiple possible causes of for the development of acute respiratory failure with pleurodesis that include, in addition to a systemic inflammatory response syndrome due to sterile talc, re-expansion pulmonary edema, excessive dosing of talc, and sepsis due to bacterial contamination of talc or due to bacterial entry at chest tube placement or thoracoscopy. Tenuous respiratory status in end-stage chronic obstructive pulmonary disease (COPD) or restrictive lung disease due to malignancy or pulmonary fibrosis, excessive premedication, or widespread metastatic disease in a terminal patient could also be causative. Furthermore, talc from different sources may contain contaminants or be of variable particle size; these could be important factors. Others have suggested causation by finding talc in bronchoalveolar lavage (BAL) fluid, lungs, and other organs in experimental animals and humans; however, every chemical instilled into the pleural space will enter the circulation through the inflammed pleural membrane and, thus, talc would be expected to be found in BAL fluid of patients without respiratory failure.

	CONCLUSION

TOP PLEURODESIS MECHANISMS OF TALC PLEURODESIS CONCLUSION REFERENCES

Talc by either poudrage or slurry is the most ideal pleurodesis agent available and is being prematurely vilified by association by some on the basis of circumstantial, retrospective evidence. Every patient receiving talc pleurodesis, and especially those with an associated respiratory event, should be analyzed as is currently being done by the Cancer and Leukemia Group B (CALGB) in a large, multicenter, prospective study so that this dilemma can be resolved.

	References

TOP PLEURODESIS MECHANISMS OF TALC PLEURODESIS CONCLUSION REFERENCES

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