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Adult respiratory distress syndrome following intrapleural instillation of talc
J THORAC CARDIOVASC
SURG
85:523-526, 1983
Adult respiratory distress syndrome following intrapleural instillation of talc After intrapleural instillation of talc for sclerosis of malignant pleural effusions, dyspnea occurred in three patients, progressed gradually over 72 hours, and culminated in acute respiratory failure characterized by bilateral diffuse pulmonary infiltrates with normal pulmonary artery occlusion pressures. Two patients recovered and one died. The chronological similarity of the sequence offever, dyspnea, and respiratory failure in the absence of documented infection or other conditions that predispose to the adult respiratory distress syndrome (ARDS) suggests that intrapleural talc may have induced the syndrome in these patients through unknown mechanisms. This experience emphasizes that other agents are preferable for initial attempts to promote pleural symphysis in the palliation of recurrent malignant effusions. When talc is used in patients who are unresponsive to tetracycline, we suggest clinical monitoring for respiratory compromise for 72 hours after the procedure.
Jean E. Rinaldo, M.D., Gregory R. Owens, M.D., and Robert M. Rogers, M.D., Pittsburgh, Pa.
Recurrent pleural effusion from suspected or confirmed malignant disease remains a difficult clinical problem. Over the past two decades, instillation of sclerosing substances into the pleural space has been the preferred method of treatment. A number of sclerosing agents have been used successfully, 1 including thiotepa, nitrogen mustard, quinacrine, tetracycline," and talc. 3 All of these agents can cause transient febrile reactions and local pain. Except for myelosuppression associated with the use of nitrogen mustard and thiotepa, we have not found a report of lifethreatening side effects of these agents. We now report three cases of acute respiratory failure typical of adult respiratory distress syndrome (ARDS) after pleural sclerosis by talc. Case reports CASE 1. A 35-year-old man had presented I year previously with pleural effusions, ascites, and lymphadenopathy. Poorly differentiated lymphocytic lymphoma was diagnosed from an axillary lymph node biopsy. Despite chemotherapy and radiotherapy of abdominal lymph nodes, ascites and
Fromthe Pulmonary Division, Department of Medicine,and Critical Care Medicine Division, Department of Anesthesiology, University of Pittsburgh, School of Medicine, Pittsburgh, Pa., and the Oakland Veterans Administration Medical Center. Received for publication May II, 1982. Accepted for publication June 17, 1982. Address for reprints: Dr. Rinaldo, Division of Pulmonary Medicine, University of Pittsburgh, 440 ScaifeHall, Pittsburgh, Pa. 15261.
bilateral pleural effusions persisted and the patient was hospitalized for sclerosis of the right pleural cavity. Thoracentesis yielded 2,700 ml of fluid. The effusion recurred within I day. A solution containing 250 ml of saline and 10 gm of talc was instilled into the right pleural space, retained for 2 hours, and drained. That evening the patient complained of right-sided chest pain and dyspnea. A temperature elevation to 38.5° C was noted, but defervescence followed within 12 hours and the patient remained afebrile for the remainder of his illness. However, his dyspnea worsened over the next 72 hours. Furosemide-induced diuresis and thoracentesis of the contralateral pleural effusion afforded no symptomatic relief. Seventy hours after talc instillation he complained of severe dyspnea. An arterial blood gas analysis revealed a pH of 7.44, Pco, of 34 mm Hg, and P0 2 of 45 mm Hg while the patient was breathing room air. Intubation, mechanical ventilation, an Flo, of 0.75, and 15 ern H 20 of positive endexpiratory pressure (PEEP) were required to achieve an arterial P0 2 of 60 mm Hg. A chest roentgenogram demonstrated diffuse bilateral opacification not present before sclerosis (Fig. I). A Gram stain of sputum showed scant flora, sputum culture yielded no pathogens, and cultures of blood and urine were sterile. Tests for cold agglutinins, mycobacteria, and direct fluorescent antibodies to Legionella pneumophilia in tracheal aspirates were all negative. A balloon-tipped pulmonary artery catheter was then inserted. The pulmonary artery pressure was 30/20 mm Hg, with a pulmonary capillary wedge pressure (PCWP) of 12 mm Hg , suggesting that the pulmonary edema was noncardiogenic in origin. Broadspectrum antibiotics were begun empirically. Requirement for elevated inspired oxygen concentration slowly diminished, and the patient was extubated after 10 days of mechanical ventilation. He was discharged after 3 additional weeks of oxygen therapy, with eventual total resolution of the pulmonary infiltrates and dyspnea. CASE 2. An 81-year-old woman had had carcinoma of the
523
The Journal of
524 Rinaldo, Owens. Rogers
Thoracic and Cardiovascular Surgery
Fig. 1. Chest roentgenograms of Patient I. A, Forty-eight hours before talc infusion bilateral pleural effusion and left hilar mass are present. Lung fields are clear. B, Eighty hours after talc sclerosis, bilateral pulmonary infiltrates are apparent. rectum diagnosed 2 years previously, and metastatic inguinal node metastases were treated with radiation therapy without known recurrence. Five months before the present admission, she noted dyspnea and cough and a large pleural effusion was found. Pleural biopsy was not diagnostic. Thoracentesis relieved her symptoms but the effusion recurred. Because of persistent dyspnea, pleural sclerosis with tetracycline was attempted 3 months before admission but was unsuccessful. On admission, a chest roentgenogram showed a pleural effusion filling the left hemithorax. The right lung was clear. Ten grams of talc were instilled into the left pleural space, and that evening the patient complained of chest pain and dyspnea. The respirations were 30 per minute, the blood pressure 70/ 40 mm Hg, the pulse 130 beats/min, and temperature 38° C. The blood pressure responded promptly to intravenous crystalloid infusion, but dyspnea worsened progressively over the next 3 days; on the fourth day after talc instillation the patient was markedly tachypneic and cyanotic. Repeated chest roentgenograms demonstrated bilateral infiltrates. She was intubated and mechanically ventilated, requiring an Flo, of 0.5 and PEEP of 10 em H20 to maintain an arterial P0 2 of 70 mm Hg. Repetitive cultures of blood, urine, and sputum revealed no pathogens; tests for cold agglutinins and direct fluorescent antibodies for L. pneumophilia were negative. A balloontipped pulmonary artery catheter yielded a pulmonary artery pressure of 40/22 and PCWP of 9 mm Hg. Despite broadspectrum antibiotics and supportive therapy, the patient died of respiratory failure after I month of ventilatory support, with persistent bilateral roentgenographic opacification. CASE 3. A 37-year-old woman was hospitalized for left pleural effusion and increasing abdominal girth. Laparotomy revealed ovarian adenocarcinoma. After an uneventful postoperative course, she was hospitalized for therapy of recurrent pleural effusions. She denied dyspnea. A chest tube was inserted into the left pleural space and drained 1,800 ml of
fluid. On the following day, 10 gm of talc in normal saline was inserted into the pleural space and drained after 2 hours. That night her temperature rose to 38.2° C and tachycardia developed. She complained of dyspnea. which worsened during the next 3 days. Seventy-two hours after talc was instilled the patient appeared markedly dyspneic. An arterial blood gas analysis revealed a pH of 7.36, Pco, of 47 mm Hg, and P0 2 of 60 mm Hg while the patient breathed supplemental oxygen. Chest roentgenograms (Fig. 2) showed bilateral infiltrates not seen prior to sclerosis. A pulmonary artery catheter revealed a pulmonary arterial pressure of 32/18 mm Hg and a PCWP 12 mm Hg. Cultures of blood and sputum were negative but cultures of urine grew Klebsiella pneumonia in a concentration of 104 /ml. Therefore tobramycin and ampicillin were added despite the low colony count of organisms in the urine. Computed tomography of the chest revealed a loculated anterior pleural effusion, which was drained without improvement in pulmonary gas exchange. Mechanical ventilation with PEEP was continued for 3 days. Six days after talc instillation the patient was extubated but continued to complain of dyspnea and to require supplemental oxygen. Three days later, symptoms of dyspnea began to abate and arterial oxygenation improved. She was finally discharged after 41 days of hospitalization, without residual respiratory symptoms.
Discussion We report three similar cases of idiopathic acute respiratory failure typical of ARDS after attempted pleural sclerosis with talc. These cases occurred within a 4 month period at the Presbyterian-University Hospital in Pittsburgh. In all three cases, systemic symptoms occurred shortly after talc instillation. Dyspnea was noted
Volume 85 Number 4
April,1983
ARDS after pleural sclerosis
5 25
Fig. 2. Chest roentgenograms of Patient 3. A, Immediately after tube thoracostomy lung fields are clear. B, Seventy-two hours after talc sclerosis, bilateral infiltrates are present.
within 24 hours and progressed to respiratory failure necessitating intubation and mechanical ventilation over the ensuing 72 hours. One patient ultimately died, but the other two patients survived after a prolonged period of respiratory support. We recognize that in complex clinical situations the "cause" of ARDS cannot always be defined precisely. Primary pulmonary infections with viral agents, Mycoplasma, or Pneumocystis cannot be excluded entirely, since all three patients were judged to be too unstable to undergo open lung biopsy and were treated with broad-spectrum antibiotics empirically. Infection seems unlikely, however, since all three patients remained afebrile except for transient temperature elevation after talc instillation and since only one patient (Patient 1) had previously received immunosuppressive chemotherapeutic drugs. Reexpansion pulmonary edema is also unlikely, since all infiltrates were bilateral. None of the three patients manifested prolonged hypotension after pleural drainage, so that ARDS due to hypovolemic shock also seems implausible. Talc, known to be an effective pleural sclerosing agent for almost 50 years, 5 was initially used at the time of open thoracotomy. 5-7 Later, Chambers" showed that instillation of a talc suspension through a thoracostomy tube was also an effective means of achieving pleural symphysis. Alder and Sayek" described a series of 41
patients with malignant pleural effusions, who underwent sclerosis with 10 gm of talc through a thoracostomy tube in a manner similar to that used in our cases. The procedure was successful in preventing recurrence in 38 of 40 cases. Respiratory insufficiency was not reported as a complication of talc instillation in this series. However, it is possible that sporadic episodes of respiratory failure have occurred but have not been attributed to the procedure. It is likely that the insidious onset of respiratory distress over a 72 hour period that we observed would not have been attributed to talc except that the clustering of three cases in a short period of time raised the possibility of a relationship between talc sclerosis and subsequent unexplained respiratory failure. To determine the incidence and specificity of respiratory failure after talc sclerosis in our institution, we retrospectively reviewed the records of patients who underwent pleural sclerosis in the 6 month period during which the three reported cases occurred. During this period, 10 patients underwent sclerosis with 500 to 1,000 mg of tetracycline. Of these patients, one died 3 days after tetracycline sclerosis. This patient was judged to be terminally ill at the time sclerosis was performed. None of the other patients had fever, pulmonary infiltrates, dyspnea, or systemic symptoms, but two had recurrence of effusion. In addition to the three
The Journal of Thoracic and Cardiovascular
526 Rinaldo, Owens, Rogers
Surgery
cases reported here, one other patient underwent sclerosis with talc. That patient received 5 gm of talc, which is half the recommended dose. Sclerosis was unsuccessful and no side effects occurred. In another patient, sclerosis with thiotepa was successful, without complication. Talc causes a wide spectrum of pulmonary disorders when inhaled or injected intravenously. When it is inhaled, the clinical spectrum ranges from respiratory distress? in massive inhalation to pulmonary fibrosis!" in chronic subacute inhalation. Injected intravenously, most commonly by drug abusers;'! talc causes perivascular granulomatosis'< and has been implicated, although not definitively, in sudden death in heroin addicts" and in the genesis of heroin-induced pulmonary edema.':' Mechanisms by which talc instilled in the pleural space could cause permeability pulmonary edema in some patients are entirely speculative. It is unlikely that talc incites only a local inflammatory response, which alters the permeability of the adjacent pulmonary microvasculature, since this would not account for bilateral pulmonary infiltrates. Alternatively, pleural talc could cause ARDS by promoting a systemic inflammatory response, which affects the lung through bloodborne mediators. For example, the activation of the alternate complement pathway has been implicated in the pathogenesis of ARDS in diverse clinical settings. 15 Talc is 'not a uniform substance. It contains impurities and is variable depending on its geologic origin. Thus it is conceivable that the talc instilled contained unusual injurious substances that contributed to respiratory distress in our patients. Tetracycline is reported to be effective in a single instillation in 90% of cases'" and causes a minimal incidence of fever and pleuritic chest pain. For this reason, we recommend tetracycline as the initial agent of choice for pleural sclerosis. The apparent association of respiratory failure with intrapleural talc instillation in these three cases suggests that several days' clinical observation for potential respiratory compromise is indicated if talc is used in patients who are unresponsive to tetracycline.
REFERENCES
2 3
4
5
6 7
8
9 10 11
12 13
14
15
16
Anderson CB, Philpott GW, Ferguson TB: The treatment of malignant pleural effusions. Cancer 33:916-922, 1974 Wallach HW: Intrapleural tetracycline for malignant pleural effusions. Chest 68:510-512, 1975 Adler RH, Sayek I: Treatment of malignant pleural effusion. A method using tube thoracostomy and talc. Ann Thorac Surg 22: 8-15, 1976 Bethune N: Pleural poudrage. New technic for the deliberate production of pleural adhesions as preliminary to lobectomy. 1 THoRAc SURG 4:251-261, 1935 Camishion RC, Gibbon lH lr, Nealon TF lr: Talc poudrage in the treatment of pleural effusion due to cancer. Surg Clin North Am 42:1521-1526,1962 Jones GR: Treatment of recurrent malignant pleural effusions by iodized talc pleurodesis. Thorax 24: 69-73, 1969 Pearson FG, MacGregor DC: Talc poudrage for malignant pleural effusion. 1 THoRAc CARDIOVASC SURG 51:732-738, 1966 Chambers lS: Palliative treatment of neoplastic pleural effusion with intercostal intubation and talc instillation. \Vest 1 Surg 66:26-28, 1958 Motomatsu K, Adachi H, Uno T: Two infant deaths after inhaling baby powder. Chest 75:448-450, 1979 Hunt AC: Massive pulmonary fibrosis from the inhalation of talc. Thorax 11:287-294, 1956 Arnett EN, Battle WE, Russo 1V, Roberts WC: Intravenous injection of talc-containing drugs intended for oral use. A cause of pulmonary granulomatosis and pulmonary hypertension. Am 1 Med 60:711-718,1976 Hopkins GB, Taylor DG: Pulmonary talc granulomatosis. Am Rev Respir Dis 101:101-104,1970 Siegel H, Bloustein P: Continuing studies in the diagnosis and pathology of death from intravenous narcotics. 1 Forensic Sci 15: 179-184, 1970 Silber R, Clerkin EP: Pulmonary edema in acute heroin poisoning. Report of four cases. Am 1 Med 27: 187-192, 1959 lacob HS, Craddock PR, Hammerschmidt DE, Moldow CF: Complement-induced granulocyte aggregation. An unsuspected mechanism of disease. N Engl 1 Med 302:789-794, 1980 Bayly TC, Kisner DL, Sybert A, MacDonald lS, Tsou E, Schein PS: Tetracycline and quinacrine in the control of malignant pleural effusions. A randomized trial. Cancer 41: 1188-1192, 1978
SURG
85:523-526, 1983
Adult respiratory distress syndrome following intrapleural instillation of talc After intrapleural instillation of talc for sclerosis of malignant pleural effusions, dyspnea occurred in three patients, progressed gradually over 72 hours, and culminated in acute respiratory failure characterized by bilateral diffuse pulmonary infiltrates with normal pulmonary artery occlusion pressures. Two patients recovered and one died. The chronological similarity of the sequence offever, dyspnea, and respiratory failure in the absence of documented infection or other conditions that predispose to the adult respiratory distress syndrome (ARDS) suggests that intrapleural talc may have induced the syndrome in these patients through unknown mechanisms. This experience emphasizes that other agents are preferable for initial attempts to promote pleural symphysis in the palliation of recurrent malignant effusions. When talc is used in patients who are unresponsive to tetracycline, we suggest clinical monitoring for respiratory compromise for 72 hours after the procedure.
Jean E. Rinaldo, M.D., Gregory R. Owens, M.D., and Robert M. Rogers, M.D., Pittsburgh, Pa.
Recurrent pleural effusion from suspected or confirmed malignant disease remains a difficult clinical problem. Over the past two decades, instillation of sclerosing substances into the pleural space has been the preferred method of treatment. A number of sclerosing agents have been used successfully, 1 including thiotepa, nitrogen mustard, quinacrine, tetracycline," and talc. 3 All of these agents can cause transient febrile reactions and local pain. Except for myelosuppression associated with the use of nitrogen mustard and thiotepa, we have not found a report of lifethreatening side effects of these agents. We now report three cases of acute respiratory failure typical of adult respiratory distress syndrome (ARDS) after pleural sclerosis by talc. Case reports CASE 1. A 35-year-old man had presented I year previously with pleural effusions, ascites, and lymphadenopathy. Poorly differentiated lymphocytic lymphoma was diagnosed from an axillary lymph node biopsy. Despite chemotherapy and radiotherapy of abdominal lymph nodes, ascites and
Fromthe Pulmonary Division, Department of Medicine,and Critical Care Medicine Division, Department of Anesthesiology, University of Pittsburgh, School of Medicine, Pittsburgh, Pa., and the Oakland Veterans Administration Medical Center. Received for publication May II, 1982. Accepted for publication June 17, 1982. Address for reprints: Dr. Rinaldo, Division of Pulmonary Medicine, University of Pittsburgh, 440 ScaifeHall, Pittsburgh, Pa. 15261.
bilateral pleural effusions persisted and the patient was hospitalized for sclerosis of the right pleural cavity. Thoracentesis yielded 2,700 ml of fluid. The effusion recurred within I day. A solution containing 250 ml of saline and 10 gm of talc was instilled into the right pleural space, retained for 2 hours, and drained. That evening the patient complained of right-sided chest pain and dyspnea. A temperature elevation to 38.5° C was noted, but defervescence followed within 12 hours and the patient remained afebrile for the remainder of his illness. However, his dyspnea worsened over the next 72 hours. Furosemide-induced diuresis and thoracentesis of the contralateral pleural effusion afforded no symptomatic relief. Seventy hours after talc instillation he complained of severe dyspnea. An arterial blood gas analysis revealed a pH of 7.44, Pco, of 34 mm Hg, and P0 2 of 45 mm Hg while the patient was breathing room air. Intubation, mechanical ventilation, an Flo, of 0.75, and 15 ern H 20 of positive endexpiratory pressure (PEEP) were required to achieve an arterial P0 2 of 60 mm Hg. A chest roentgenogram demonstrated diffuse bilateral opacification not present before sclerosis (Fig. I). A Gram stain of sputum showed scant flora, sputum culture yielded no pathogens, and cultures of blood and urine were sterile. Tests for cold agglutinins, mycobacteria, and direct fluorescent antibodies to Legionella pneumophilia in tracheal aspirates were all negative. A balloon-tipped pulmonary artery catheter was then inserted. The pulmonary artery pressure was 30/20 mm Hg, with a pulmonary capillary wedge pressure (PCWP) of 12 mm Hg , suggesting that the pulmonary edema was noncardiogenic in origin. Broadspectrum antibiotics were begun empirically. Requirement for elevated inspired oxygen concentration slowly diminished, and the patient was extubated after 10 days of mechanical ventilation. He was discharged after 3 additional weeks of oxygen therapy, with eventual total resolution of the pulmonary infiltrates and dyspnea. CASE 2. An 81-year-old woman had had carcinoma of the
523
The Journal of
524 Rinaldo, Owens. Rogers
Thoracic and Cardiovascular Surgery
Fig. 1. Chest roentgenograms of Patient I. A, Forty-eight hours before talc infusion bilateral pleural effusion and left hilar mass are present. Lung fields are clear. B, Eighty hours after talc sclerosis, bilateral pulmonary infiltrates are apparent. rectum diagnosed 2 years previously, and metastatic inguinal node metastases were treated with radiation therapy without known recurrence. Five months before the present admission, she noted dyspnea and cough and a large pleural effusion was found. Pleural biopsy was not diagnostic. Thoracentesis relieved her symptoms but the effusion recurred. Because of persistent dyspnea, pleural sclerosis with tetracycline was attempted 3 months before admission but was unsuccessful. On admission, a chest roentgenogram showed a pleural effusion filling the left hemithorax. The right lung was clear. Ten grams of talc were instilled into the left pleural space, and that evening the patient complained of chest pain and dyspnea. The respirations were 30 per minute, the blood pressure 70/ 40 mm Hg, the pulse 130 beats/min, and temperature 38° C. The blood pressure responded promptly to intravenous crystalloid infusion, but dyspnea worsened progressively over the next 3 days; on the fourth day after talc instillation the patient was markedly tachypneic and cyanotic. Repeated chest roentgenograms demonstrated bilateral infiltrates. She was intubated and mechanically ventilated, requiring an Flo, of 0.5 and PEEP of 10 em H20 to maintain an arterial P0 2 of 70 mm Hg. Repetitive cultures of blood, urine, and sputum revealed no pathogens; tests for cold agglutinins and direct fluorescent antibodies for L. pneumophilia were negative. A balloontipped pulmonary artery catheter yielded a pulmonary artery pressure of 40/22 and PCWP of 9 mm Hg. Despite broadspectrum antibiotics and supportive therapy, the patient died of respiratory failure after I month of ventilatory support, with persistent bilateral roentgenographic opacification. CASE 3. A 37-year-old woman was hospitalized for left pleural effusion and increasing abdominal girth. Laparotomy revealed ovarian adenocarcinoma. After an uneventful postoperative course, she was hospitalized for therapy of recurrent pleural effusions. She denied dyspnea. A chest tube was inserted into the left pleural space and drained 1,800 ml of
fluid. On the following day, 10 gm of talc in normal saline was inserted into the pleural space and drained after 2 hours. That night her temperature rose to 38.2° C and tachycardia developed. She complained of dyspnea. which worsened during the next 3 days. Seventy-two hours after talc was instilled the patient appeared markedly dyspneic. An arterial blood gas analysis revealed a pH of 7.36, Pco, of 47 mm Hg, and P0 2 of 60 mm Hg while the patient breathed supplemental oxygen. Chest roentgenograms (Fig. 2) showed bilateral infiltrates not seen prior to sclerosis. A pulmonary artery catheter revealed a pulmonary arterial pressure of 32/18 mm Hg and a PCWP 12 mm Hg. Cultures of blood and sputum were negative but cultures of urine grew Klebsiella pneumonia in a concentration of 104 /ml. Therefore tobramycin and ampicillin were added despite the low colony count of organisms in the urine. Computed tomography of the chest revealed a loculated anterior pleural effusion, which was drained without improvement in pulmonary gas exchange. Mechanical ventilation with PEEP was continued for 3 days. Six days after talc instillation the patient was extubated but continued to complain of dyspnea and to require supplemental oxygen. Three days later, symptoms of dyspnea began to abate and arterial oxygenation improved. She was finally discharged after 41 days of hospitalization, without residual respiratory symptoms.
Discussion We report three similar cases of idiopathic acute respiratory failure typical of ARDS after attempted pleural sclerosis with talc. These cases occurred within a 4 month period at the Presbyterian-University Hospital in Pittsburgh. In all three cases, systemic symptoms occurred shortly after talc instillation. Dyspnea was noted
Volume 85 Number 4
April,1983
ARDS after pleural sclerosis
5 25
Fig. 2. Chest roentgenograms of Patient 3. A, Immediately after tube thoracostomy lung fields are clear. B, Seventy-two hours after talc sclerosis, bilateral infiltrates are present.
within 24 hours and progressed to respiratory failure necessitating intubation and mechanical ventilation over the ensuing 72 hours. One patient ultimately died, but the other two patients survived after a prolonged period of respiratory support. We recognize that in complex clinical situations the "cause" of ARDS cannot always be defined precisely. Primary pulmonary infections with viral agents, Mycoplasma, or Pneumocystis cannot be excluded entirely, since all three patients were judged to be too unstable to undergo open lung biopsy and were treated with broad-spectrum antibiotics empirically. Infection seems unlikely, however, since all three patients remained afebrile except for transient temperature elevation after talc instillation and since only one patient (Patient 1) had previously received immunosuppressive chemotherapeutic drugs. Reexpansion pulmonary edema is also unlikely, since all infiltrates were bilateral. None of the three patients manifested prolonged hypotension after pleural drainage, so that ARDS due to hypovolemic shock also seems implausible. Talc, known to be an effective pleural sclerosing agent for almost 50 years, 5 was initially used at the time of open thoracotomy. 5-7 Later, Chambers" showed that instillation of a talc suspension through a thoracostomy tube was also an effective means of achieving pleural symphysis. Alder and Sayek" described a series of 41
patients with malignant pleural effusions, who underwent sclerosis with 10 gm of talc through a thoracostomy tube in a manner similar to that used in our cases. The procedure was successful in preventing recurrence in 38 of 40 cases. Respiratory insufficiency was not reported as a complication of talc instillation in this series. However, it is possible that sporadic episodes of respiratory failure have occurred but have not been attributed to the procedure. It is likely that the insidious onset of respiratory distress over a 72 hour period that we observed would not have been attributed to talc except that the clustering of three cases in a short period of time raised the possibility of a relationship between talc sclerosis and subsequent unexplained respiratory failure. To determine the incidence and specificity of respiratory failure after talc sclerosis in our institution, we retrospectively reviewed the records of patients who underwent pleural sclerosis in the 6 month period during which the three reported cases occurred. During this period, 10 patients underwent sclerosis with 500 to 1,000 mg of tetracycline. Of these patients, one died 3 days after tetracycline sclerosis. This patient was judged to be terminally ill at the time sclerosis was performed. None of the other patients had fever, pulmonary infiltrates, dyspnea, or systemic symptoms, but two had recurrence of effusion. In addition to the three
The Journal of Thoracic and Cardiovascular
526 Rinaldo, Owens, Rogers
Surgery
cases reported here, one other patient underwent sclerosis with talc. That patient received 5 gm of talc, which is half the recommended dose. Sclerosis was unsuccessful and no side effects occurred. In another patient, sclerosis with thiotepa was successful, without complication. Talc causes a wide spectrum of pulmonary disorders when inhaled or injected intravenously. When it is inhaled, the clinical spectrum ranges from respiratory distress? in massive inhalation to pulmonary fibrosis!" in chronic subacute inhalation. Injected intravenously, most commonly by drug abusers;'! talc causes perivascular granulomatosis'< and has been implicated, although not definitively, in sudden death in heroin addicts" and in the genesis of heroin-induced pulmonary edema.':' Mechanisms by which talc instilled in the pleural space could cause permeability pulmonary edema in some patients are entirely speculative. It is unlikely that talc incites only a local inflammatory response, which alters the permeability of the adjacent pulmonary microvasculature, since this would not account for bilateral pulmonary infiltrates. Alternatively, pleural talc could cause ARDS by promoting a systemic inflammatory response, which affects the lung through bloodborne mediators. For example, the activation of the alternate complement pathway has been implicated in the pathogenesis of ARDS in diverse clinical settings. 15 Talc is 'not a uniform substance. It contains impurities and is variable depending on its geologic origin. Thus it is conceivable that the talc instilled contained unusual injurious substances that contributed to respiratory distress in our patients. Tetracycline is reported to be effective in a single instillation in 90% of cases'" and causes a minimal incidence of fever and pleuritic chest pain. For this reason, we recommend tetracycline as the initial agent of choice for pleural sclerosis. The apparent association of respiratory failure with intrapleural talc instillation in these three cases suggests that several days' clinical observation for potential respiratory compromise is indicated if talc is used in patients who are unresponsive to tetracycline.
REFERENCES
2 3
4
5
6 7
8
9 10 11
12 13
14
15
16
Anderson CB, Philpott GW, Ferguson TB: The treatment of malignant pleural effusions. Cancer 33:916-922, 1974 Wallach HW: Intrapleural tetracycline for malignant pleural effusions. Chest 68:510-512, 1975 Adler RH, Sayek I: Treatment of malignant pleural effusion. A method using tube thoracostomy and talc. Ann Thorac Surg 22: 8-15, 1976 Bethune N: Pleural poudrage. New technic for the deliberate production of pleural adhesions as preliminary to lobectomy. 1 THoRAc SURG 4:251-261, 1935 Camishion RC, Gibbon lH lr, Nealon TF lr: Talc poudrage in the treatment of pleural effusion due to cancer. Surg Clin North Am 42:1521-1526,1962 Jones GR: Treatment of recurrent malignant pleural effusions by iodized talc pleurodesis. Thorax 24: 69-73, 1969 Pearson FG, MacGregor DC: Talc poudrage for malignant pleural effusion. 1 THoRAc CARDIOVASC SURG 51:732-738, 1966 Chambers lS: Palliative treatment of neoplastic pleural effusion with intercostal intubation and talc instillation. \Vest 1 Surg 66:26-28, 1958 Motomatsu K, Adachi H, Uno T: Two infant deaths after inhaling baby powder. Chest 75:448-450, 1979 Hunt AC: Massive pulmonary fibrosis from the inhalation of talc. Thorax 11:287-294, 1956 Arnett EN, Battle WE, Russo 1V, Roberts WC: Intravenous injection of talc-containing drugs intended for oral use. A cause of pulmonary granulomatosis and pulmonary hypertension. Am 1 Med 60:711-718,1976 Hopkins GB, Taylor DG: Pulmonary talc granulomatosis. Am Rev Respir Dis 101:101-104,1970 Siegel H, Bloustein P: Continuing studies in the diagnosis and pathology of death from intravenous narcotics. 1 Forensic Sci 15: 179-184, 1970 Silber R, Clerkin EP: Pulmonary edema in acute heroin poisoning. Report of four cases. Am 1 Med 27: 187-192, 1959 lacob HS, Craddock PR, Hammerschmidt DE, Moldow CF: Complement-induced granulocyte aggregation. An unsuspected mechanism of disease. N Engl 1 Med 302:789-794, 1980 Bayly TC, Kisner DL, Sybert A, MacDonald lS, Tsou E, Schein PS: Tetracycline and quinacrine in the control of malignant pleural effusions. A randomized trial. Cancer 41: 1188-1192, 1978