© 2004 American Thoracic Society
Systematic Response to Talc PleurodesisTo the Editor:We read with interest the recent article by Montes and colleagues (1) describing increased systemic talc deposition in high- as opposed to low-dose talc slurry pleurodesis. Whereas the authors clearly support the theory that severe complications after pleurodesis are due to disseminated talc, they correctly state that this hypothesis has not been proved. We report a fatal case of talc pleurodesis syndrome in which complete autopsy failed to demonstrate systemic dissemination of talc. An 84-year-old woman with a history of polycythemia rubra vera (controlled with venesection) presented with a right-sided pleural effusion. Video-assisted thoracoscopy with biopsy of the parietal pleura and poudrage with high-dose talc was undertaken. Eighteen hours after surgery she became hypotensive and hypoxic. Chest radiograph showed patchy bilateral infiltrates in both mid and lower zones. Although afebrile, her white cell count increased dramatically from 10.9 x 109/L before surgery to 49.4 x 109/L on the second postoperative day. She died 58 hours after surgery with intractable hypotension, severe hypoxia, and acute renal failure. Results of blood and sputum cultures were negative. At autopsy, extreme care was taken to stop talc from the right pleural cavity contaminating other organs. Despite extensive histologic examination of all organs, including many blocks from each lobe of both lungs, no talc was demonstrable outside the massively inflamed right pleural cavity. The lungs were hyperemic and the alveolar spaces distended by neutrophils—morphologically very similar to early bacterial pneumonia. No other cause of hypoxia or vascular collapse was found (the pleural effusion was shown to be due to an early mesothelioma). Given the degree of pleural inflammation and systemic neutrophilia in this case, we postulate that vascular collapse was due to a systemic inflammatory response syndrome in the absence of circulating talc. Furthermore, we suggest that pleural inflammation may trigger pulmonary inflammation through paracrine and circulating factors without the need for talc to enter the lungs. We propose that this "aseptic pneumonitis" is the cause of opacification and hypoxia seen in talc pleurodesis syndrome rather than diffuse alveolar damage, the usual histologic correlate of acute respiratory distress syndrome, to which it is often attributed without pathologic correlation. We conclude that regardless of the risk for dissemination, the severe local inflammatory reaction incited by talc may be sufficient to cause a fatal systemic response.
Royal North Shore Hospital Sydney, Australia FOOTNOTES Conflict of Interest Statement: A.J.G., M.N.M., and S.F.T. have no declared conflict of interest. REFERENCES
From the Authors: The term "acute respiratory distress syndrome" (ARDS) refers to a clinical picture consisting of dyspnea, tachypnea, cyanosis, and diffuse alveolar infiltrates on chest radiograph. Pathologic findings include diffuse alveolar damage with neutrophils, macrophages, erythrocytes, hyaline membranes, and protein-rich edema fluid in the alveolar spaces, capillary injury and disruption of the alveolar epithelium (1). Cases of acute lung failure occurring after talc pleurodesis have been considered to be ARDS owing to a similar clinical pattern, but pathologic descriptions in these cases have not been reported. The hypothesis that pulmonary talc dissemination accounts for acute lung failure observed after talc pleurodesis is supported by the following facts: (1) whenever investigated, talc has been found in all patients with acute lung failure after talc pleurodesis, whether in lung or bronchoalveolar lavage samples, but not in patients without acute lung failure (see our article [2] for more details); (2) acute lung failure has not been described after nontalc pleurodesis; (3) in animal studies, talc dissemination to the lung has been reported, especially at high doses (2) and with smaller talc particles (3); (4) most patients undergoing acute lung failure after talc pleurodesis received talc from the United States, where smaller talc particles are used (see DISCUSSION and REFERENCES in our article [2]). The case reported by Gill and colleagues clearly describes a lethal acute lung failure after talc pleurodesis in which no talc was found in the lungs of the patient. In our opinion, there may be two explanations for this fact. First, several lung problems may account for the clinical acute respiratory failure observed in the patient reported by Gill and colleagues. Characteristic pathologic features of ARDS are lacking, so this patient could have had another process. As an example, negativity of cultures does not preclude the possibility that this older woman with bilateral infiltrates, blood leukocytosis, and neutrophil lung infiltration had a lung infection. Second, talc produces pleurodesis by inflaming the pleura, and therefore acute lung failure could be caused either by a direct effect of talc particles disseminated to the lung or indirectly by inflammatory mediators released from the inflamed pleura.
a Hospital Universitari Vall d'Hebron Barcelona, Spain FOOTNOTES Conflict of Interest Statement: J.F., J.F.M., and J.G-V. have no declared conflict of interest. REFERENCES
To the Editor: The article by Montes and colleagues (1) significantly and importantly relates pleural talc doses in rabbits to the animal's response. Higher doses of talc were associated with greater talc migration and created local and distant inflammatory responses. The authors' connection of these findings to the reported development of acute respiratory distress syndrome (ARDS) in humans is germane. We report here the first case where a human served as her own control after ARDS occurred after a high dose of pleural talc insufflation (7.5–10 g). When 3 g of the same talc was administered to the contralateral thorax, ARDS did not develop (2). Dyspnea due to recurrent left malignant pleural effusion developed in a 59-year-old woman 11 years after mastectomy for breast cancer. At thoracoscopy—for pleurodesis—the pleura was covered with 1- to 10-mm tumor nodules. During the procedure, an error was made in talc insufflation, which by protocol was to be 10 ml (5 g) or less. This resulted in 15 to 20 ml (7.5–10 g) of talc insufflation. After the procedure, the patient was weak, dyspneic, and febrile. Fever persisted for 10 days. The chest tube was removed after 72 hours when drainage was less than 150 ml per 24 hours (total drainage 650 ml over 72 hours). On the fourth day after the procedure, worsening respiratory distress led to intubation and mechanical ventilation for 7 days. ARDS was diagnosed, with slow improvement to hospital discharge on Day 31 of hospital stay, and eventual recovery. Seven months later, a symptomatic right-sided malignant effusion developed. Chest computed tomography scan showed a successful left pleurodesis. After a right-sided thoracoscopy and insufflation of 3 g talc, the patient's hospital course was uneventful with discharge on the third postoperative day. Radiographs 50 days later showed a partly successful pleurodesis; no further thoracenteses were needed. Her talc dosages were calculated to be 142 to 189 mg/kg on the left and 57 mg/kg on the right, which coincidentally are comparable with the rabbit study of 200 and 50 mg/kg doses (1). We believe this case presents further evidence that talc overdosing may cause ARDS. Although our talc (Spectrum Chemical Supply, Gardena, CA) has a relatively small mean diameter of 5.5 µm, prospective data entry of 286 consecutive thoracoscopic talc poudrages and 9 talc slurry treatments revealed no other case of ARDS (2). As the authors—and many others—indicate, doses greater than 5 g in talc pleurodesis should be avoided.
Southern California Permanente Medical Group Harbor City, California FOOTNOTES Conflict of Interest Statement: Y.A. has no significant financial interest in the subject. REFERENCES
From the Authors: The case presented by Dr. Aelony suggests that acute lung failure after talc pleurodesis is dose-dependent. Because, as demonstrated in our study, pulmonary talc dissemination after pleurodesis is also dose-dependent in the rabbit model (1), Aelony's report further supports the hypothesis that acute lung failure and lung talc dissemination are related. To definitely prove that, in human beings, talc overdose may cause acute lung failure, randomized studies with different talc doses should be performed. However, it is obvious that the low frequency of acute lung failure and also ethical reasons preclude these studies from being performed. In the future, more studies on pulmonary histology and plasma levels of inflammatory cytokines in patients undergoing acute lung failure after talc pleurodesis should be done. Meanwhile, we agree with Dr. Aelony that doses less than 5 g should only be used in talc pleurodesis, and talc should not be administered when pleural biopsy is performed during pleurodesis.
a Hospital Universitari Vall d'Hebron Barcelona, Spain FOOTNOTES Conflict of Interest Statement: J.F., J.F.M., and J.G-V. have no declared conflict of interest. REFERENCES
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