Dr. Tse Hoi Nam, Department of Medicine, Kwong Wah Hospital
Background
Talc is an inert, tri-layered, magnesium silicate that has significant lubricative property. The formula of talc is H2Mg3(SiO3)4 or Mg3Si4O10(OH)2. It is insoluble in water but is slightly soluble in diluted mineral acids. Pure talc does not exist since it is often contaminated with other minerals like magnesite, calcite, serpentine, quartz etc. Moreover, the morphology and particle size of talc varies greatly in different countries. Talc is cheap and widely available. Apart from medical use in pleurodesis, talc is widely used in industries such as paper making, plastic, paint and coatings, rubber, food, electric cable, pharmaceuticals, cosmetics, ceramics, etc.
Mechanism of talc pleurodesis
Medical talc is asbestos-free. It was first used for pleurodesis in 1935 by surgeon Norman Bethune. Talc induces an intense intrapleural inflammatory response and subsequent pleurodesis by production of different cytokines like interleukin-8, vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β). (1)
Efficacy of talc pleurodesis
Talc is more effective to induce pleurodesis and prevent recurrence when compared to other agents like tetracycline. The Cochrane review (2) of pleurodesis for malignant effusions found that the relative risk of non-recurrence was 1.34 in favor of talc when compared with bleomycin, tetracycline, mustine, or tube drainage alone.
Side effects and complication of Talc pleurodesis
Despite its high efficacy, the safety of intrapleural application of talc has been a hot debate in recent years because of reports of talc-related serious complications like respiratory failure and acute respiratory distress syndrome (ARDS). Minor adverse effects of talc pleurdesis include fever and pain. There is also risk of cardiovascular complications like arrthymias and hypotension. Serious complications of talc pleurodesis are rare and these include infections, respiratory failure and acute respiratory distress syndrome (ARDS).
1) Infections
In order to reduce risk of infections, sterilized talc is recommended in all cases. There was a study (3) comparing the efficacy and cost of sterilization of talc. It suggested that dry heat, gamma irradiation and ethylene oxide gas are all equally effective means for sterilization of talc, with dry heat being the least expensive. The study also revealed that the sterility of talc can be maintained at 90 days after sterilization. However, the exact sterile shelf life of the talc is unknown. Some authorities recommend repeating culture of sterilized talc at 6 months and 1 year after sterilization to confirm its sterility before pleurodesis. Unfortunately, the process of sterilization, packaging and culture would put up extra cost. Furthermore, even with sterilized talc, there is still a small risk of infection. Empyema has been reported with both talc slurry and poudrage.
2) Acute respiratory distress syndrome (ARDS)
Incidence of talc induced ARDS
The exact incidence of talc induced ARDS is still controversial and it varies greatly in different cases series and studies. Rehse’s study (4) reported the rate of ARDS to be as high as 9% after talc pleurodesis, while Cardillo’s study (5) had demonstrated no significant risk. In the recent CALGB study (6) comparing talc slurry versus poudrage for pleurodesis in 486 patients with malignant effusion, 2.3% mortality from respiratory failure after talc pleurodesis was shown.
Proposed mechanism of ARDS
Systemic embolization of talc particles from pleural cavity has been proposed to be the underlying mechanism of ARDS. The exact mechanism of embolization is unknown although there are some postulations that talc particles may gain entry into the systemic circulation via the small pores of parietal pleura and the parietal lymphatic channels. This has received support from some animal studies. Werebe (7) showed that there was a significant deposition of talc particles in every organ of rats within 24-48 hours after instillation of 10-20mg talc slurry into their pleural cavities.
Effect of particle size
Particle size may have strong implication for development of ARDS. The diameter of pleural stomata in humans is around 6.2 µm. Smaller talc particles may therefore pass through and get into the systemic circulation. Thus, the smaller the particule size of talc, the greater the side effect it may produce.
Ferrer (8) also demonstrated that the deposition of talc particles in lungs was much more significant (60% vs. 20%) in rabbits with pleural spaces instillated with small-size talc (max. diameter 8.36µm) compared to those instillated with large-size talc (max. diameter 12.0µm).
A recent randomized clinical trial in symptomatic malignant pleural effusions (9) further strengthened this theory. The “mixed talc” group (with smaller particle size) resulted in greater increase in A-a gradient, a decrease in pO2, an increase in C-reactive protein and a higher frequency of fever (41% vs. 4%) at 48hours after pleurodesis in comparison to the “graded talc” group with small particles excluded. This clinical study strongly suggested that graded talc may reduce the incidence of adverse effects.
The particle sizes of talc vary greatly among different countries. The French talc (Steritalc®), with size calibrated with a median particle diameter of 31.3µm, is widely utilized in Europe and possesses a much bigger particle size than those preparations under use in US. This may explain the relatively lower reported rates of ARDS in Europe. Moreover, in a recent multi-centre prospective cohort study (10) on 558 patients with malignant pleural effusions revealed no case of ARDS with 4g calibrated large particle talc (Steritalc®).
Conclusion
Talc is an effective agent for pleurodesis. ARDS is a potential life-threatening condition which may be related to the dose and particle size of talc. Current evidence suggests that calibrated large particle size talc may be associated with a lower risk of systemic complications.
References
1. Genofre et.al. Inflammation and clinical repercussions of pleurodesis induced by intrapleural talc administration. Clinic 2007; 62: 627
2. Shaw P et.al. Corhrane database systemic review 2004: CD 002916
3. Kennedy Lisa et.al. Sterilization of Talc for Pleurodesis: Available Techniques, Efficacy, and Cost Analysis. Chest 1995; 107: 1032-34
4. Rehse DH etal. Respiratory failure following talc pleurodesis. Am J surg 1999; 177: 437-440
5. Cardillo G et.al. Long term follow up of video-assisted talc pleurodesis in malignant recurrent pleural effusions. Eur J Cardio-thoracic Surg 2002; 21: 302-306
6. Carolyn M et.al. Phase III intergroup study of Talc Poudrage vs Talc slurry sclerosis for malignant pleural effusion. Chest 2005; 127: 909-915)
7. Werebe EC et al. Systemic distribution of talc after intrapleural administration: an experimental study in rats. Chest 2002; 122: 1737-1741
8. Ferrer F et al. Influence of particle size on extrapleural talc dissemination after talc slurry pleurodesis. Chest 2002; 122: 1018-1027
9. Nick A. Maskell et al. Randomized trial describing lung inflammation after pleurodesis with talc of varying particle size. Am J Respir Crit Care Med 2004; 170: 377-382
10. Julius P Janssen et al. Safety of pleurodesis with talc poudrage in malignant pleural effusion: a prospective cohort study. Lancet 2007; 369, 9572
