The Effects of Talc Pleurodesis on Growing Swine By Eugene

D. McGahren,

W.

Gerald

Teague, Jr, Terry Charlottesville,

0 Talc pleurodesis is an effective means of preventing recurrent pneumothorax. We have successfully applied talc pleurodesis with thoracoscopy in children with cystic fibrosis presenting with pneumothorax. However, little is known about the effects of talc pleurodesis on lung compliance in growing children. Therefore, six young pigs (10 weeks old, weighing 15 ? 1 kg) were prepared for study. In each pig, one hemithorax underwent thoracoscopy and talc pleurodesis (TALC). The other hemithorax underwent either thoracoscopy alone or no procedure (CONTROL). Dynamic and static respiratory mechanics were studied 5 and 10 weeks later. Air flow and airway pressure were measured to calculate dynamic transpulmonary and transrespiratory compliance, and static transpulmonary compliance. At 5 weeks, dynamic transpulmonary and transrespiratory compliance were less in the TALC lungs when compared with CONTROL lungs. At 10 weeks, the differences in dynamic transpulmonary and transrespiratory compliance between the TALC and CONTROL lungs had resolved. Static compliance was lower in the TALC lungs than in the CONTROL lungs at both 5 and 10 weeks, but this was significant only at 10 weeks. There was an improvement in static compliance in the TALC lungs between 5 and 10 weeks, but thfs only approached significance. At autopsy, there were marked adhesions and pleural thickening in the talc lungs. Histological examination demonstrated no differences in lung parenchyma between the TALC lungs and the CONTROL lungs. Talc pleurodesis causes a temporary impairment in dynamic transpulmonary and transrespiratory compliance that resolves with time and growth. Static compliance is more persistently compromised, but a trend toward improvement with time and growth exists. Talc pleurodesis does not affect the lung parenchyma. These data indicate that talc pleurodesis has minimal long-term effects on pulmonary compliance in growing pigs, and are consistent with clinical findings of the safety of talc pleurodesis in humans. @ 1990 by WA?. Saunders Company. INDEX fibrosis.

WORDS:

Pneumothorax:

talc

pleurodesis;

cystic

PONTANEOUS pneumothorax is a significant clinical problem in patients with cystic fibrosis. Different methods of treatment have been used over the years, including tube thoracostomy, pleurodesis with a variety of chemical agents, pleural abrasion, and pleurectomy. Talc, in particular, has been recognized as an effective agent for pleurodesis, but in the past its use was limited due to contamination with asbestos. However, the currently available preparations of purified talc are free of this impurity. Since 1984, at the University of Virginia Health Sciences Center, we have treated nine children with cystic fibrosis suffering from spontaneous pneumothorax, using USP purified talc introduced via thoracoscopy. None of these pa-

S

Journal

of Pediatric

Surgery,

Vol 25,

No 11 (November).

1990:

pp 1147-l

Flanagan, Virginia

Bonnie

White,

and

Bradley

M.

Rodgers

tients have experienced recurrence of their pneumothoraces on the treated side and none have suffered complications from talc pleurodesis. The ideal therapy for spontaneous pneumothorax should prevent recurrence with absolute certainty, but should not compromise the mechanical function of the lungs or pleura. This is particularly important in the young patient with cystic fibrosis with minimal respiratory reserve. The present study was designed to evaluate the effects of talc pleurodesis on the lung and pleura in a rapidly growing porcine model. MATERIALS

AND

METHODS

Six healthy pigs, aged 10 weeks and weighing 15 + 1 kg, were prepared for thoracoscopy and pleurodesis. Each pig was anesthetized with pentabarbital (5 to 10 mg intravenously [IV]), intubated with a cuffed no. 6 endotracheal tube, and paralyzed with pancuronium (0.1 mg/kg IV) that was titrated to effect continued paralysis. The pigs were ventilated on a Harvard ventilator at a tidal volume of 10 mL/kg with anesthesia maintained with halothane. In three pigs, thoracoscopy and talc pleurodesis were performed on one hemithorax, and thoracoscopy without pleurodesis was performed on the opposite hemithorax. In three pigs unilateral thoracoscopy and talc pleurodesis were performed, with no procedure performed in the opposite hemithorax. The technique for thoracoscopy and pleurodesis has been previously described.’ A 5.5-mm trocar was used as the introducer for the Storz rod lens telescope. (Karl Storz EndoscopyAmerica, Inc. Culver City, CA.) In the hemithoraces that did not undergo pleurodesis, the thoracoscope was removed after visual exploration of the entire hemithorax. In the hemithoraces in which talc pleurodesis was performed, a second trocar was inserted into the same intercostal space, about 5 cm from the first trocar, and served as the introducer for a talc insufflation cannula (Fig 1). The entire lung and pleural space were examined. Approximately 6.0 g of USP purified sterile talc were then insufflated uniformly over the visceral and parietal pleural surfaces. All pigs tolerated the procedures well and none showed any clinical evidence of respiratory distress, All of the pigs were studied 5 weeks later, at which time they weighed an average of 34 + 1 kg. The animals were anesthetized, paralyzed, intubated, and ventilated as before. To selectively ventilate the right or left hemithoraces for the measurement of differential compliance, the appropriate main stem bronchus was occluded under flexible bronchoscopic guidance (Olympus BF2 3C4, Olympus Corp, New Hyde Park, NY) with a SF Fogarty arterial embolecFrom the Department of Surgery, University of Virginia Health Sciences Center, and Children’s Medical Center, Charlottesville, VA. Presented at the 21st Annual Meeting of the Canadian Association of Paediatric Surgeons, Edmonton, Alberta, September 20-23, 1989. Address reprint requests to Bradley M. Rodgers, MD, Box 181, Department of Surgery, University of Virginia Health Sciences Center, Charlottesville. VA 22908. 0 1990 by W.B. Saunders Company. 0022-3468/90/25’1 I-001 1$03.00/O 151

1147

McGAHREN

Table

1. Data

from

Experiments

Dynamic Transpulmonq (mL/cm)

Compliance

ET AL

Transrespiratcq hL/cm)

Static: Transpulmonary hL/cm)

5 weeks TALC

Fig 1. TALC insufflation cannula. Sterile USP pure talc is pieced in the reservoir and dusted with the pneumatic bulb over the entire pleural surface.

(n =

17 k 2

16 + 1

35 k 4

In =

5)

39 * 9

27 + 2

52 f 7

TALC (n = 5) CONTROL (n =

5)

60 k 11 69 + 15

58 + 11 56 + 10

CONTROL lOWWItS

5)

NOTE. All data given as mean

tomy catheter (American V. Mueller, McGaw Park, IL). For study of the left hemithorax, the right eparterial bronchus was occluded with a separate 4F Fogarty catheter. Following the appropriate mainstem bronchus occlusion, the tidal inflation volume was reduced by 55% to selectively ventilate the left hemithorax and by 45% in the case of the right. Dynamic transrespiratory pressure was measured with a differential transducer (Validyne MP 45, Northridge, CA) attached on one side to the proximal airway opening and on the other to the ambient atmosphere. Dynamic transpulmonary pressure was measured with the transducer attached on one side to the proximal airway opening and on the other to a balloon catheter (volume, 0.5 to 1 mL, partially inflated) inserted into the distal third of the intrathoracic esophagus. Gas flow was measured by a pneumotachygraph (Fleisch no. 2, OEM, Richmond, VA) inserted between the connection of the endotracheal tube and the ventilator circuitry. The flow and pressure signals were digitized (AH Devices A/D Converter, San Rafael, CA) continuously with a microcomputerbased data acquisition system (Apple He, Cupertino, CA) at 15-millisecond intervals and stored on floppy diskettes. At least five inflations were analyzed per ventilated hemithorax. Dynamic transrespiratory and transpulmonary compliance were calculated by the method of least mean squares2 Static transpulmonary compliance was measured under passive conditions by inflating the right or left lungs to 400 mL with a calibrated pump (Hans Rudolph, Kansas City, MO) and recording the corresponding transpulmonary pressure plateau. These studies were again performed at 10 weeks following pleurodesis when the pigs weighed 62 + 1 kg. Data from two pigs at this interval were incomplete, because one pig died of an anesthetic complication and the data from one hemithorax of one pig was lost due to an error in computer storage. The pigs were then euthanized with pentobarbital sodium (10 to 30 mg/kg IV) and the lungs were fixed with the airway opening exposed to 25 cm pressure with 10% formalin. The data from those hemithoraces exposed to thoracoscopy alone as compared with those not subject to any procedure were not significantly different by Student’s t test for unpaired samples. As such, the measurements from these two sample groups were pooled and were designated as CONTROL. Measurements from hemithoraces subjected to thoracoscopy and talc pleurodesis were designated TALC. Student’s t test for unpaired samples was used to compare results between these two sample groups. Student’s t test for paired samples was used to analyze paired measurements at 5 and 10 weeks within each group. A probability value of 5.05 indicated a statistically significant difference.

61 +9 118 + 20

f SD.

TROL sides (P < .05). However, at 10 weeks, there was no significant difference between the two groups. Figure 3 shows dynamic transrespiratory compliance in the TALC and CONTROL hemithoraces in the pigs at 5 and 10 weeks postprocedure. At 5 weeks, transrespiratory compliance was significantly lower in the TALC sides than in the CONTROL sides (P K .005), but at 10 weeks there was no significant difference measured between the two groups. Figure 4 shows that static transpulmonary compliance was lower in the TALC hemithoraces than in the CONTROL hemithoraces at both 5 and 10 weeks postprocedure. The difference in the two groups approached significance at 5 weeks (P < .07) and was significant at 10 weeks (P < .02). There was improvement noted in static compliance on the TALC sides between the 5- and lo-week observation periods, but this did not reach statistical significance in this interval (P < .07).

At autopsy there were extensive pleural adhesions with thickening of both the visceral and parietal pleura in the TALC hemithoraces. Chest roentgenograms obtained in these animals at 10 weeks indicated minimal loss of volume in the TALC hemithoraces (Fig 5A). There was evidence of pleural thickening with tenting of the diaphragm in some of these animals (Fig 5B). Hemithoraces that had undergone thoracoscopy alone had a few filmy adhesions, but no pleural thickening at autopsy. Histological examination of the lungs showed no inflammatory changes in the lung parenchyma in either the TALC or CONTROL lungs. There was marked pleural thickening noted on the TALC sides (Fig 6).

RESULTS

The data from each of the experiments is summarized in Table 1. Figure 2 shows dynamic transpulmonary compliance in the TALC and CONTROL hemithoraces in the pigs at 5 and 10 weeks postprocedure. At 5 weeks, transpulmonary compliance was significantly lower in the TALC sides than in the CON-

Fig 2. Dynamic transpulmonary TALC and CONTROL hemithoraces dure. l P c .05.

compliance (mL/cm) in the 5 and 10 weeks postproce-

1149

TALC PLEURODESIS

0 W.ek.

Fig 3. Dynamic TALC and CONTROL dure. l P < .005.

to I,...

transrespiratory hemithoraces

compliance (mL/cm) in the at 5 and 10 weeks postprooe-

DISCUSSION

The use of talc as an agent for pleurodesis was introduced in 1935.3 Initially, it was used only sporadically because of its real and purported side effects. In particular, early preparations were contaminated with asbestos, thus potentially predisposing recipients to the development of mesothelioma. However, later reports have indicated that talc is a safe and effective agent for pleurodesis with few untoward side effects.“8 Our own clinical experience has supported this view.’ Furthermore, contemporary purified preparations of talc do not contain asbestos, thus eliminating the risks of mesothelioma. There are very few studies of lung function in patients having undergone talc pleurodesis, but those available suggest little compromise of pulmonary function. Paul et al” reported no significant decrease in expired lung volume using bronchospirometric measurements at 2 to 4 months postprocedure in four adult patients who received talc pleurodesis for spontaneous pneumothorax. Lange et al” found a reduction in both forced expiratory volume in 1 second (FEV,) and forced vital capacity (FVC) in a long-term follow-up of patients having undergone talc pleurodesis for spontaneous pneumothorax. Only one patient of 46 in this series suffered any clinical manifestation of this restriction. Dynamic compliance as defined by corresponding tidal volume and pressure changes during ventilation is inherently a flow-limited measurement. As such, it reflects not only elastic recoil but the distribution of ventilation in the lung itself.‘2”3 Therefore, the significant reduction in hemithoracic dynamic transpulmo-

Fig 4. Static transpulmonary and CONTROL hemithoraces l P i .oz.

compliance (mL/cm) in the TALC at 5 and 10 weeks postprocedure.

Fig 5. Chest roentgenograms at 10 weeks postprocedure. TALC right hemithorax-CONTROL left shows minimal thickening and slight elevation of the hamidbphragm on the side. (51 TALC left hemithorax-CONTROL right, shows tenting on the TALC side (arrow) with no elevetion hemidiaphragm.

(A) pleural TALC pleural of the

McGAHREN

Fig 6. pulmonary

Histological parenchyma

specimens of (A) CONTROL and (B) TALC lungs at 10 weeks postprocedure (P) appears normal. The visceral pleura (*) on the TALC lung is thickened.

nary and transrespiratory dynamic compliance at 5 weeks may be due to flow heterogeneity and/or decreased elastic recoil. However, the corresponding static compliance data, measurements that are not affected by flow, did not show a corresponding significant reduction at 5 weeks. Thus the reduction in dynamic compliance at 5 weeks postpleurodesis could be related more to uneven flow resistance and the distribution of ventilation in the lungs than to an intrinsic reduction in elastic properties of lung.‘* The explanation for the effect of pleurodesis on the dynamic compliance in the lungs at 5 weeks is twofold. First, these studies do not exclude the possibility that the absolute lung volume might be decreased on the sclerosed side. However, this did not appear to be the case on radiographs or at autopsy. Second, pleurodesis may exert an effect on the distribution of intrapleural pressures by virtue of complete obliteration of the visceral and parietal pleural interface. These explanations are only speculative, and further studies of the regional changes in ventilation following pieurodesis are needed before concluding that the transient reduction in dynamic elastic recoil noted in these studies at 5 weeks is due to such mechanisms. Static compliance, as defined by recoil pressure at a predetermined volume, was less in the TALC chests at both 5 and 10 weeks, but this difference was significant only at 10 weeks. Of note, static elastic recoil did improve in each of the pigs from 5 to 10 weeks, but the magnitude of this improvement was less in the TALC

(original

magnification

x 125).

ET AL

The

group (Fig 4). Again, this difference may reflect a reduction in absolute lung volume on the sclerosed side as well as talc effects on pleura. The latter would be expected to have greater effects on static rather than dynamic measurements. Because dynamic compliance is only transiently altered in the TALC lungs, we speculate that pleural changes must have had the most significant impact on lung recoil as reinforced by data showing decreased static compliance in the TALC lungs. This restriction was more statistically apparent at 10 weeks, even though compliance increased. These findings are consistent with the correlation between pleural thickening and restrictive changes in the lung noted in the report by Lange et al.” The results of this study suggest that talc pleurodesis causes an early impairment in dynamic transpulmonary and transrespiratory compliance, but that these changes resolve with time and growth. Lung recoil, as measured by static compliance is compromised early, and for a longer period of time, but these changes tend to improve with time and growth. The mechanisms accounting for these changes are uncertain, but may relate to changes in regional pleural pressure caused by pleural symphysis. Histological findings suggest that pleurodesis has no effect on the lung parenchyma itself. These data are consistent with previous reports of the safety and efficacy of talc pleurodesis for the treatment of spontaneous pneumothorax, and support its use in the growing patient.

REFERENCES 1. Rodgers BM, Moazam F, Talbert J: Thoracoscopy in children. Ann Surg 189:176-180, 1979 2. Roy R, Powers SE, Kimball WR: Estimation of respiratory parameters by the method of covariance ratios. Comp Biomed Res 7121-39, 1974

3. Bethune N: Pleural poudrage: New techniques for deliberate production of pleural adhesions as preliminary to lobectomy. J Thorac Cardiovasc Surg 4:25 l-261, 1935 4. Pearson FG, MacGregor DC: Talc poudrage for malignant pleural effusion. J Thorac Cardiovasc Surg 51:732-738, 1966

TALC

PLEURODESIS

5. Adler RH, Rappole BW: Recurrent malignant pleural effusions and talc powder aerosol treatment. Surgery 62:1000-1006, 1967 6. Weissberg D, Kaufman M, Zurkowski Z: Pleuroscopy in patients with pleural effusion and pleural masses.Ann Thorac Surg 29:205-208, 1980 7. Weissberg D: Talc pleurodesis: A controversial issue. Polmon Coevr 37:291-294, 1981 8. Weissberg D, Kaufman M: Diagnostic and therapeutic pleuroscopy-Experience with 127 patients. Chest 78:732-735, 1980 9. Tribble CG, Selden RF, Rodgers BM: Talc poudrage in the treatment of spontaneous pneumothoraces in patients with cystic fibrosis. Ann Surg 204:677-680, 1986

1151

10. Paul JS, Beattie EJ, Blades B: Lung function in poudrage treatment of recurrent spontaneous pneumothorax. J Thorac Surg 22:52-61, 1951 11. Lange F, Mortensen J, Groth S: Lung function 22-35 years after treatment of idiopathic spontaneous pneumothorax with talc poudrage or simple drainage. Thorax 43:559-561, 1988 12. Otis AB, McKerrow CB, Bartlett RA, et al: Mechanical factors in distribution of pulmonary ventilation. J Appl Physiol 8:427-443, 1956 13. Woolcock AJ, Vincent NJ, Macklem PT: Frequency dependence of compliance as a test for obstruction in the small airways. J Clin Invest 48: 1047- 1106, 1969