Randomized Trials Describing Lung Inflammation after Pleurodesis with Talc of Varying Particle Size
We report two trials describing whether talc pleurodesis with a mean particle size of less than 15 um (“mixed” talc) produces more lung and systemic inflammation than tetracycline or “graded” talc (most particles <10 um were removed).
First, 20 patients with malignant effusions received tetracycline or mixed talc. Changes in lung and systemic inflammation from lung clearance scans, oxygen saturations, and C-reactive protein from baseline to 48 hours after pleurodesis were recorded. Lung inflammation (change in isotope clearance, talc- 9.26, SD 14.3 vs. tetracycline 4.10, SD 13.8 minutes; difference =13.4; 95% confidence interval [CI], 26.6 to 0.2; p 0.05) and systemic inflammation (change in C-reactive protein, talc 198 SD 79.2 vs. tetracycline 74 SD 79.4 g/L; difference 124; 95% CI, 50 to 199;p = 0.004) were greater after talc.
Second, 48 patients received mixed or graded talc, and gas exchange was assessed from changes in the alveolar–arterial oxygen gradient. Mixed talc worsened gas exchange (oxygen gradient change, mixed 2.17 SD 1.74 kPa, 16.3 13.1 mm Hg vs. graded 0.72 SD 2.46 kPa 5.4 18.5 mm Hg, difference 1.45; 95% CI, 0.2 to 2.7; p 0.03) and induced more systemic inflamma-tion than graded talc. We conclude that the routine use of graded talc for pleurodesis would reduce the morbidity of this procedure.
Keywords: acute respiratory distress syndrome; pleural effusion; pleu-rodesis; randomized trial; talc
There are approximately 300,000 pleural effusions caused by cancer in the United Kingdom and United States each year (1). Many of these are symptomatic and require pleurodesis for their control. Sterile talc is the most effective agent for pleurodesis (2–4), but there are concerns that it may not be safe. There are over 30 reported cases of acute respiratory distress syndrome after intrapleural talc administration, and 9 of these have been fatal (2, 5–13). In a recent international survey of 859 pulmonolo-gists, over half reported cases of respiratory failure after talc pleu-rodesis (14).
This toxicity is seen after both talc slurry and talc poudrage (8). It is hypothesized that this toxicity may relate to the use of talc preparations that include particles of small ( <15 um) size because most reports of acute respiratory distress syndrome are from countries where preparations including small particle sizes are prevalent (2, 8, 10, 11). In contrast, large observational series from countries that use talc containing only large particle sizes describe few serious adverse events (3, 15). There are no randomized trials assessing the potential toxicity of varying talc preparations and no studies describing whether the reported cases of acute respiratory distress syndrome are isolated idiosyncratic adverse reactions or the severe end of a spectrum of diffuse lung damage that could be detected from subtle indices of lung inflammation. This article reports two randomized trials addressing this question.
We hypothesized that inflammation in the lung contralateral to a pleurodesis might be detectable by 99mtechnetium-labeled DTPA lung scanning because this test is capable of identifying subtle lung inflammation in other settings (16–19). This hypothesis led to the two randomized trials reported here. In the first, we assessed whether talc with a mean particle size of less than 15 um (“mixed” particle size talc—the standard U.S. and U.K. preparation) produced DTPA scan–detectable lung inflammation and hypoxemia after pleurodesis compared with a non–talc-based control (tetracycline pleurodesis).
In the light of the results of this first study, we then performed the second trial to compare the severity of arterial hypoxemia, fever, and systemic inflammation after pleurodesis with mixed (standard United Kingdom and United States) talc and talc that has had the majority of particles less than 10 um size removed (mean particle size of < 25 um—“graded” particle size talc—the standard European preparation). Despite its role in original hypothesis testing, DTPA scanning was not used in the second trial, as the results of the first had rendered this complex investigation unnecessary (20).
References
1. Dresler CM. Systemic distribution of talc. Chest 1999;116:266.
2. Kennedy L, Rusch VW, Strange C, Ginsberg RJ, Sahn SA. Pleurodesis using talc slurry. Chest 1994;106:342–346.
3. Weissberg D, Ben Zeev I. Talc pleurodesis: experience with 360 patients. J Thorac Cardiovasc Surg 1993;106:689–695.
4. Webb WR, Ozmen V, Moulder PV, Shabahang B, Breaux J. Iodized talc pleurodesis for the treatment of pleural effusions. J Thorac Cardiovasc Surg 1992;103:881–885.
5. Brant A, Eaton T. Serious complications with talc slurry pleurodesis. Respirology 2001;6:181–185.
6. Rinaldo JE, Owens GR, Rogers RM. Adult respiratory distress syndrome following intrapleural instillation of talc. J Thorac Cardiovasc Surg 1983;85:523–526.
7. Bouchama A, Chastre J, Gaudichet A, Soler P, Gibert C. Acute pneumonitis with bilateral pleural effusion after talc pleurodesis. Chest 1984; 86:795–797.
8. Rehse DH, Aye RW, Florence MG. Respiratory failure following talc pleurodesis. Am J Surg 1999;177:437–440.
9. Migueres J, Jover A. Indications for intrapleural talc under pleuroscopic control in malignant recurrent pleural effusions: based on 26 cases. Poumon Coeur 1981;37:295–297.
10. Marel M, Skacel Z, Bednar M, Julak J, Light RW. Corynebacterium parvum, bleomycin and talc in the treatment of malignant pleural effusions. J Bon 1998;1:165–170.
引用/广播