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Talc-induced interstitial pneumonitis with respiratory failure.

Pleurodesis is routinely used for the treatment of recurrent pleural effusion. Among the many agents employed, talc is the most frequently used with a low rate of complications and a high rate of success (1,2). Among the complications, pleuritic chest pain and fever are the most common, but they do not last long and usually are resolved with anti-inflammatory therapy. Cases of acute pneumonia and acute respiratory distress syndrome are rare but, when they occur, require intensive treatment and are associated with a high rate of death (2).

In this report we describe one patient in whom an acute interstitial pneumonitis with acute respiratory failure developed after talc pleurodesis.

CASE HISTORY

A 39-year-old woman was admitted to our unit in October 2006 complaining of rapidly progressing dyspnoea and non-productive cough. One year before, the patient had undergone radical mastectomy with axillary lymphadenectomy because of infraductal, infiltrating carcinoma of the right breast followed by prosthetic reconstruction. The patient had no history of occupational exposure. Chest X-ray and computed tomography (CT) scan demonstrated a left pleural effusion. A left thoracentesis was performed and 1500 ml of serous fluid was drained. Two days later, a new left pleural effusion was noted, with dyspnoea and cough. Because of the rapid reaccumulation of the effusion, a pleurodesis through a video-assisted thoracoscopy was performed. The parietal pleura was fragile and hyperaemic, with pedunculated protuberances which bled easily. Biopsies on these protuberances were followed by complete drainage of the pleural fluid and nebulisation of 2 g talc with a particle size of 10 [micro]m to 30 [micro]m (Talc De Luzenac, Toulouse, France). A drainage tube was inserted.

The procedure was uncomplicated apart from a small amount of bleeding. Four hours later, the patient became dyspnoeic and febrile (39[degrees]C), on physical examination of the lungs the patient had rales and decreased breath sounds in the right lung. Arterial blood values at room air were: pH=7.41, PC[O.sub.2]=47 mmHg, P[O.sub.2]=56 mmHg with an oxygen saturation of 79%. Chest X-ray showed diffuse pulmonary interstitial infiltrates (Figure 1A). A thoracic CT scan showed a good result from the left pleurodesis, but patchy, subpleural, peripheral, bibasilar and reticular abnormalities with airspace consolidation, rather than ground glass opacification, more accentuated on the right lung (Figure 1B). Fibreoptic bronchoscopic examination demonstrated normal airways and bronchoalveolar lavage was performed. The analysis of the lavage fluid showed no abnormality in differential cell count. Her respiratory status progressively deteriorated and she was transferred to the intensive care unit (ICU). In the ICU the results of routine laboratory tests (haematology, biochemistry and urinanlysis) were normal, except for elevation in enzyme values (SGOT=109 IU per litre, normal <20, SGPT=129 IU per litre, normal <20 and LDH=1138 IU per litre, normal <240). Echocardiography and the D-dimer dosage were normal. Searches for cytomegalovirus, Epstein-Barr virus, respiratory syncytial virus, adenovirus, Legionella pneumophila, Mycoplasma pneumoniae, Pneumocystis carinii, Mycobacterium tuberculosis and fungi were negative. In the ICU, the patient underwent cycles of continous positive air pressure with helmet and medical therapy with antibiotics, prednisone and bronchodilators. After 10 days of intensive treatment, she became progressively afebrile, showed marked clinical improvement and was discharged home 15 days after the admission to the ICU, with oral prednisone with good CT scan images (Figure 2). At follow-up on March 2008 she was in good health.

[FIGURE 1 OMITTED]

DISCUSSION

Our patient suffered from an unusual complication a few hours after talc pleurodesis. Chest X-ray and CT scan showed patterns of interstial pneumonitis and the blood gas analysis indicated compromised gas exchange with severe hypoxaemia. Echocardiography ruled out a cardiac origin for the respiratory failure and the D-dimer dosage excluded the diagnosis of pulmonary embolism. Moreover she denied any occupational exposure and an infectious process was ruled out by the negativity of her blood analysis. The dramatic onset of her illness shortly after talc pleurodesis strongly suggested talc to be the cause of her pulmonary distress.

[FIGURE 2 OMITTED]

Talc was first used by Bethune in 1935 for pleurodesis and since then it has been widely employed, either as talc poudrage or a talc slurry (3). Compared with other agents used for chemical pleurodesis, talc is effective, inexpensive, widely available and associated with few and minor complications. A survey of pneumologists in five English-speaking countries found that talc (poudrage or slurry) was the most preferred agent for inducing pleurodesis and was associated to a higher success rate compared with other agents (4).

However, concerns remain about the safety of talc. In the same survey, talc (both poudrage or slurry) was associated with significantly more complications (4). Usually these complications such as chest pain, fever, nausea are entirely benign and are resolved with anti-inflammatory therapy.

Talc-related acute interstitial pneumonitis with respiratory distress is a rare complication following talc pleurodesis requires intensive treatment and it is associated with a high mortality rate. Milanez de Campos, in his large series of 550 patients who had undergone talc pleurodesis, reported an occurrence of respiratory failure distress syndrome with bilateral interstitial infiltrates in seven patients (1.3%) with three deaths (2). An autopsy performed in one of these patients, demonstrated the presence of talc crystals in almost all organs (2). Sahn reviewed studies about the occurrence of respiratory failure after talc pleurodesis and, among 4030 patients, identified 41 patients (1%) with this serious complication (5).

The causes of this complication remain largely unknown. Intrapleural talc can clearly migrate or be transported into the lungs and other organs (2). It has also been suggested that the occurrence of pneumonitis is related to systemic absorption of talc with the subsequent production and release of inflammatory mediatorsb. Nasreen demonstrated that when mesothelial cells are incubated with talc, citokynes such as interleukin-8 and monocyte chemotactic protein-1 are released (7), and a randomised trial suggested that post-pleurodesis hypoxaemia is due to generalised lung inflammation as well as increased systemic inflammation (8). However, patients with malignant pulmonary effusion may have substantial interstitial pulmonary disease with low oxygen saturation, which may not be clinically evident (9).

The varying occurrence of acute respiratory failure in different countries may suggest that this serious complication might be linked to talc preparation. In fact, Ferrer studied eight different talc preparations used for pleurodesis and found a marked difference in the size of the particles and in the types of contaminants of the talc preparations (10). The occurrence of respiratory failure was also attributed to the dose of talc used. Rinaldo reported the occurrence of three cases of acute respiratory distress with bilateral infiltrates after the use of 10 g of talc (11), Kennedy reported that five of 58 patients treated with 10 g of talc had respiratory failure (12), however respiratory failure can develop after much lower doses of talc, as shown in the present case and in reports by others (2,13). Further, the occurrence of this complication has been attributed to the magnitude of the particles of the talc used. A randomised trial demonstrated that mixed talc (with 50% of it being less than 10 [micro]m in size) produces more lung inflammation and hypoxaemia than graded talc (with less than 50% of particles smaller than 20 [micro]m) (8). A prospective cohort study found that the use of 4 g of large-particle talc (mean size 24[+ or -]5 [micro]m) was not associated with the development of acute respiratory distress (14), however respiratory failure can also develop with the use of even larger particle talc, as shown in the present case in which talc particle sizes of 10 [micro]m to 30 [micro]m were employed.

In conclusion, although talc pleurodesis is widely employed, it is not an entirely benign procedure, but carries definite--albeit uncommon--risks of serious complications. Therefore close surveillance of the patient and a high index of suspicion are mandatory.

REFERENCES

(1.) Light RW Talc for pleurodesis? Chest 2002; 122:1506-1508.

(2.) de Campos JR, Vargas FS, de Campos Werebe E, Cardoso P, Teixeira LR, Jatene FB et al. Thoracoscopy talc poudrage: a 15-year experience. Chest 2001; 119:801-806.

(3.) Bethune N. Pleural poudrage: new technique for deliberate production of pleural adhesions as preliminary to lobectomy. J Thorac Surg 1935; 4:251-261.

(4.) Lee YCG, Baumann MH, Maskell NA, Waterer GW, Eaton TE, Davies RJO et al. Pleurodesis practice for malignant pleural effusions in five English-speaking countries: survey of pulmonologists. Chest 2003; 124:2229-2238.

(5.) Sahn SA. Is talc indicated for pleurodesis? Pro: talc should be used for pleurodesis. J Bronchology 2002; 9:223-227.

(6.) Marchi E, Vargas FS, Acencio MMP, Antonangelo L, Teixeira LR, Genofre EH et al. Talc and silver nitrate induce systemic inflammatory effects during the acute phase of experimental pleurodesis in rabbits. Chest 2004; 125:2268-2277.

(7.) Nasreen N, Hartman DL, Mohammed KA, Antony VB. Talc-induced expression of C-C and C-X-C chemokines and intercellular adhesion molecule-1 in mesothelial cells. Am J Respir Crit Care Med 1998; 158:971-978.

(8.) Maskell NA, Lee YCG, Gleeson FV, Hedley EL, Pengelly G, Davies RJO. Randomized trials describing lung inflammation after pleurodesis with talc of varying particle size. Am J Respir Crit Care Med 2004; 170:377-382.

(9.) Dresler CM, Olak J, Herndon JE 2nd, Richards WG, Scalzetti E, Fleishman SB et al. Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion. Chest 2005; 127:909-915.

(10.) Ferrer J, Villarino MA, Tura JM, Traveria A, Light RW Talc preparations used for pleurodesis vary markedly from one preparation to another. Chest 2001; 119:1901-1905.

(11.) Rinaldo JE, Owens GR, Rogers RM. Adult respiratory distress syndrome following intrapleural instillation of talc. J Thorac Cardiovasc Surg 1983; 85:523-526.

(12.) Kennedy L, Rusch VW, Strange C, Ginsberg RJ, Sahn SA. Pleurodesis using talc slurry. Chest 1995; 106:342-346.

(13.) Bouchama A, Chastre J, Gaudichet A, Soler P, Gibert C. Acute pneumonitis with bilateral pleural effusion after talc pleurodesis. Chest 1984; 86:795-797.

(14.) Janssen JP, Collier G, Astoul P, Tassi GF, Noppen M, Rodriguez-Panadero F et al. Safety of pleurodesis with talc poudrage in malignant pleural effusion: a prospective cohort study. Lancet 2007; 369:1535-1539.

S. GRIFFO *, A. MUSUMECI *, G. DE LUCA ([dagger]), A. SACCENTI ([double dagger]), L. M. GRANDE$, P. STASSANO ([section]) *

Cardiothoracic Unit, University Federico II, Naples and Istituto Clinico Pineta Grande, Castel Volturno, Italy

* M.D., Surgeon, Cardiothoracic Unit, University Federico II.

([dagger]) M.D., Surgeon, Cardiothoracic Unit, Istituto Clinico Pineta Grande.

([double dagger]) M.D., Anaesthetist, Cardiac Anaestehsia, University Federico II.

Address for reprints: Dr S. Griffo, Via Bausan, 1, 80121 Naples, Italy.

Accepted for publication on July 23, 2008.
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Article Details
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Author:Griffo, S.; Musumeci, A.; De Luca, G.; Saccenti, A.; Grande, L.M.; Stassano, P.
Publication:Anaesthesia and Intensive Care
Article Type:Case study
Geographic Code:4EUIT
Date:Jan 1, 2009
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