Original Article. Introduction. Subjects and methods

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1 Nephrol Dial Transplant (2003) 18: DOI: /ndt/gfg042 Original Article Video-assisted thoracoscopic talc pleurodesis is effective for maintenance of peritoneal dialysis in acute hydrothorax complicating peritoneal dialysis Sydney Tang 1,2, Wing Hung Chui 3, Anthony W. C. Tang 2, Fu Keung Li 1, Wing Shun Chau 3, Yiu Wing Ho 2, Tak Mao Chan 1 and Kar Neng Lai 1 1 Department of Medicine, University of Hong Kong, Queen Mary Hospital, 2 Department of Medicine and Geriatrics, United Christian Hospital and 3 Department of Cardiothoracic Surgery, The Grantham Hospital, Hong Kong SAR, Peoples Republic of China Abstract Background. Acute, massive, unilateral hydrothorax is an uncommon but well-recognized complication of peritoneal dialysis. Its clinical course and treatment outcome after a recently advocated technique of video-assisted thoracoscopic (VATS) talc pleurodesis remains unclear. Methods and results. Between July 1998 and March 2002, among 475 CAPD patients in two regional hospitals in Hong Kong, nine patients (three men, six women, mean age 53"12 years) developed acute hydrothorax due to pleuroperitoneal communication (Rs8, Ls1) within 5.8"4.2 months (median, 5.2 m; range, 2 days to 11.6 months) of commencing peritoneal dialysis. Analysis of simultaneously obtained peritoneal and pleural fluid in all subjects only showed concordance in protein content (consistently-4 gul), while fluid glucose and lactate dehydrogenase levels were not comparable. The methylene blue test was negative (ns4). Radionuclide scan (ns6) and contrast CT peritoneography (CTP, ns3) detected pleuroperitoneal communication in half and one-third of the patients, respectively. All patients underwent pleurodesis achieved by talc insufflation into the pleural cavity under VATS guidance. All patients were successfully returned to peritoneal dialysis. After a mean followup of 18.8"12.5 months, hydrothorax recurred in one patient (at 7 months after pleurodesis), who was successfully treated by repeating the procedure. Conclusions. Hydrothorax complicating CAPD is more commonly right-sided, and tends to occur within the first year of starting peritoneal dialysis. Isotope scan and CTP are insensitive in diagnosing pleuroperitoneal communication. A low pleural fluid protein content is Correspondence and offprint requests to: Prof. K. N. Lai, Department of Medicine, University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, Peoples Republic of China. knlai@hkucc.hku.hk the most consistent biochemical finding. VATS talc pleurodesis is a safe and reliable treatment of choice that allows sustained continuation of CAPD with low recurrence rate. Keywords: CAPD; hydrothorax; pleurodesis; talc poudrage Introduction Acute hydrothorax is an uncommon but wellrecognized complication of peritoneal dialysis. Its prevalence ranges from 1.6% in adults [1] to 3% in children [2]. The diagnostic procedures of this condition remain poorly documented. Furthermore, many different methods of management have been reported with varying degrees of success. However, there is as yet no consensus of opinion to the definitive treatment of choice. Video-assisted thoracoscopic (VATS) talc pleurodesis has been advocated in recent years as a mode of treatment for hydrothorax complicating CAPD [3 5]. The efficacy, safety and outcome of this procedure has not been well characterized. In this report, we describe the clinical presentation and diagnosis of hydrothorax complicating CAPD in nine patients, and our experience in treating this condition with VATS talc pleurodesis. Subjects and methods Between July 1998 and March 2002, nine patients developed acute hydrothorax among 475 patients receiving continuous ambulatory peritoneal dialysis (CAPD) at two regional hospitals, Queen Mary Hospital and United Christian Hospital, in Hong Kong. All patients were receiving various # 2003 European Renal Association European Dialysis and Transplant Association

2 VATS talc pleurodesis for hydrothorax in CAPD combinations of standard 2-l 1.5, 2.5 anduor 4.25% dialysis solutions, with a total daily exchange volume of 6 8 l. The presenting symptoms of acute hydrothorax were either drastic reduction in ultrafiltration volume (ns9) anduor shortness of breath (ns4). There was no other symptom or sign of generalized fluid overload. The demographic data of these patients are summarized in Table 1. The methods of diagnosing leakage of peritoneal fluid into the pleural cavity are as follows. Fluid biochemistry A 2-l bag of 4.25% dextrose dialysis solution was instilled into the peritoneal cavity. After 4 h, peritoneal effluent was collected. Simultaneously, aliquots of pleural fluid were obtained by fine needle pleurocentesis. Both types of fluids were assayed for protein, glucose and lactate dehydrogenase (LDH) content. Simultaneous blood glucose, protein and LDH levels were also determined. Contrast CT peritoneography Iopamiro (150 ml) was diluted into 2 l of peritoneal dialysate solution, and the diluted contrast medium was then instilled into the peritoneal cavity through the Tenckhoff catheter. After dwelling for 2 h, 10 mm computed tomographic axial sections were taken from thorax to abdomen and pelvis. Delayed films were taken at 24 h. Peritoneopleural scintigraphy The patient performed CAPD bag exchanges as usual. The radio-isotope, Tc 99m tin-colloid, 15 mci, was injected under aseptic techniques into the peritoneal cavity via the Tenckhoff catheter. Dynamic anterior and posterior images were taken for 30 min. Delayed images were obtained at 3, 4, 6 and 24 h. Direct visualization by methylene blue injection Twenty millilitres of methylene blue was injected into a bag of dialysis solution to cause a conspicuous bluish discolouration. Diagnostic pleurocentesis was performed using fine needles. Pleural fluid was examined for the presence of similar discoloration. Temporary haemodialysis After a tentative diagnosis of pleuroperitoneal communication was established, CAPD was ceased and the subject was put on temporary haemodialysis via a dual-lumen internal jugular venous catheter. In all subjects, the initial pleural effusion completely subsided on chest radiograph taken 1 week after the commencement of haemodialysis. This, coupled with the other pertaining clinical information, is highly suggestive of a diagnosis of pleuroperitoneal communication. The subject was then ready for pleurodesis surgery. Video-assisted thoracoscopic talc pleurodesis All patients gave informed consent to undergo this procedure at a major cardiothoracic surgical centre at the Grantham Hospital. The patient was under general anaesthesia, and ventilated through a dual-lumen endotracheal tube, with the ipsilateral lung deflated. The patient was put in the decubitus position, with the side of operation (usually right) up. Three working ports were created. The first was made at the 8th intercostal space along the mid-axillary line for the introduction of the thoracoscope (Stryker 10 mm, zero degree endoscope). The other two were created at the 5th intercostal space along the anterior and posterior axillary lines. After inspection for any communication between the pleural and peritoneal cavities, and for any lung and pleural pathology, 10 g of talc powder was insufflated via a manually operated pump to ensure even distribution onto the lung surface. At the end of the procedure, two chest drains were introduced via the port sites, one toward the antero-apical region to drain air, and the other toward the postero-basal aspect to drain fluid. Postoperative care The apical drain would be removed on day 1 when the lung became fully expanded, and the basal drain would be removed when the drain output fell below 20 mluday (which typically took 3 4 days). At this point, the patient can be discharged from hospital. For the first 3 weeks after talc pleurodesis, the patient would receive intermittent haemodialysis to allow adequate fibrosis. Peritoneal dialysis was then reinstated. Table 1. Clinical characteristics and treatment outcome after VATS talc pleurodesis in nine patients with hydrothorax complicating CAPD Patient no. Gender and age Underlying renal disease Onset of hydrothorax (m) a Side affected Pleural:serum glucose gradient (mgudl) b Postoperative follow-up duration (m) Recurrence Patient 1 Fu39 Membranous Gn 8.9 R Yes c Well on CAPD 2 Mu42 Unknown 11.6 L No Died of ICH 3 Fu72 Unknown 7.4 R No Well on CAPD 4 Fu60 Diabetes mellitus 0.5 R No Fungal peritonitis, to HD 5 Fu62 Unknown 5.2 R No Well on CAPD 6 Fu66 Diabetes mellitus 10.6 R No Well on CAPD 7 Mu43 Interstitial nephritis 0.10 R No Well on CAPD 8 Fu50 Hypertension 4.8 R No Well on CAPD 9 Mu46 Neurogenic bladder 3.4 R No Well on CAPD 805 a Months after the initiation of peritoneal dialysis. b Pleural fluid glucose level minus simultaneous serum glucose level. c At 7.5 months after initial pleurodesis. Gn, glomerulonephritis; HD, haemodialysis; ICH, intracranial haemorrhage.

3 806 S. Tang et al. Statistical analysis All data were expressed as mean"standard deviation. Intergroup differences for continuous variables were assessed by one-way analysis of variance. Statistical analysis was performed using SPSS statistical software (Statistical Package for the Social Sciences, Inc., Chicago, IL). Significance was defined as P Results Nine patients (three men, six women, mean age 53" 12 years) developed massive pleural effusion within 5.8"4.2 months (median, 5.2 months; range, 2 days to 11.6 months) of commencing peritoneal dialysis. Eight patients (89%) had right-sided hydrothorax. In all cases, the pleural fluid aspirated yielded negative results for bacterial and mycobacterial cultures, and malignant cells on cytological examination. The possibility of hydrothorax arising from pleuroperitoneal communication was first assessed by analysis of simultaneous pleural and peritoneal fluid glucose, protein and LDH contents, after a 4-h dwell with 4.25% glucose peritoneal dialysis solution. As depicted in Figure 1A, the simultaneous pleural and peritoneal fluid protein concentration was similar and consistently -4 gul in all subjects, and there was no statistical difference in protein levels between the two types of body fluids. On the other hand, simultaneous pleural and peritoneal fluid glucose and LDH contents were statistically different (Figures 1B and C, respectively). Because the pleural fluid-to-serum glucose concentration gradient (spleural fluid glucose level simultaneous serum glucose level) has been reported recently to be useful in differentiating transudative pleural effusion due to pleuroperitoneal communication from other causes [6], namely congestive heart failure, hypoalbuminaemia, and fluid overload, we also computed this gradient (Table 1). The mean glucose concentration gradient between pleural fluid and serum was 140"117 mgudl (range ). Two of the nine patients had a gradient -50 mgudl. Radioisotope scintigraphy was performed in six subjects, after instillation of dialysis solution containing Tc 99m tin-colloid. Abnormal tracer activity in the thorax indicative of pleuroperitoneal leak was detected in only three (50%) subjects. Contrast CT peritoneography was carried out in three subjects, after instillation of dialysis solution containing radio-opaque contrast material. Leakage of contrast medium into the pleural cavity was only demonstrated in one subject (33%). The methylene blue test was performed on four subjects, and was negative in all. All subjects underwent VATS talc pleurodesis as described in the Subjects and Methods. The mean length of hospital stay was 4.5"1.9 days. One patient developed postoperative fever on day 1, which settled with paracetamol. Five patients experienced local wound pain at the sites of chest drain insertion, which improved with simple analgesic. There were no adverse respiratory Fig. 1. Chemical composition of simultaneous peritoneal and pleural fluid. Concentration of fluid protein (A), glucose (B) and lactate dehydrogenase (C) after a 4-h i.p. dwell of 2-l 4.25% dextrose dialysis solution. symptoms or other adverse effect from talc infusion. After a brief period of haemodialysis postoperatively, all subjects were successfully returned to peritoneal dialysis. Chest radiograph showed complete resolution of the initial effusion in all patients. After a mean follow-up of 18.8"12.5 months, hydrothorax recurred in one subject (Patient 1) at 7.5 months after initial talc pleurodesis. This patient underwent the same procedure and resumed CAPD uneventfully. After 24 months of further followup, she is currently well on CAPD without recurrence. One patient died of intracranial haemorrhage 8 months after pleurodesis, and was well maintained on CAPD at the point of the cerebrovascular accident. One patient developed severe fungal peritonitis that necessitated removal of the Tenckhoff catheter 9 months after pleurodesis, and was converted to maintenance haemodialysis thereafter. All the other patients are currently well on CAPD. There was no significant change in

4 VATS talc pleurodesis for hydrothorax in CAPD peritoneal dialysis adequacy and ultrafiltration property in terms of KtuV for urea and dialysate:plasma creatinine ratio at 4 h, respectively, before the onset of hydrothorax and after treatment by talc pleurodesis (data not shown). In addition, there was no clinically significant compromise in respiratory functional status consequent to the procedure. Discussion Massive hydrothorax is an uncommon and tedious complication of CAPD. The diagnostic approach to this condition includes chemical analysis of pleural fluid, methylene blue discoloration of the dialysate followed by thoracocentesis, imaging modalities that demonstrate transfer of radio-opaque or radioactive media across the diaphragm, and direct visualization under thoracoscopic surgery. Despite these diagnostic tools, confirming the communication is often elusive. In the analysis of fluid chemistry, the basic principle is to demonstrate a similarity between the fluid composition in the two body cavities, taking advantage of the high glucose and low protein content of the peritoneal dialysate. This is enhanced by the instillation of a dialysate with the highest sugar content shortly before thoracocentesis. However, as illustrated here, pleural fluid glucose was often not as high as one would have expected, probably secondary to its reabsorption from the pleural mesothelium. Although Chow et al. [6] reported recently that a pleural fluid-to-serum glucose concentration difference of )50 mgudl had 100% sensitivity and specificity in differentiating hydrothorax secondary to pleuroperitoneal communication from other causes, using such criterion would have missed two of nine patients (22%) with genuine pleuroperitoneal communication in the present series. Furthermore, while we instilled 4.25% dialysis solution before thoracocentesis, the concentration of the dialysate used for equilibration in Chow s series was not mentioned. It is possible that the number of genuine cases that would have been missed using such criterion might be higher if we had used a fluid of lower glucose content. Further studies, in a larger cohort, are thus imperative to better define this diagnostic cut off level. Similar to the situation with glucose levels, paired LDH levels were not helpful in suggesting a diagnosis of pleuroperitoneal communication. On the other hand, we found a high concordance rate between pleural and peritoneal fluid protein content (uniformly-4 gul), which can be used as a more reliable surrogate marker of pleuroperitoneal communication. The methylene blue test was negative in all the subjects tested. This is probably due to the pressure effect of the hydrothorax, impeding the migration of the blue dye across the diaphragm. Isotopic scanning and contrast CT peritoneography were only positive in half and a third of the patients, respectively. Thus, these imaging techniques, while being sophisticated and expensive, are not sensitive or indispensable in detecting pleuroperitoneal communication. A recent case report 807 from Ortiz and coworkers [7] showed that the yield of scintigraphy in a child with hydrothorax could be improved if the scanning was performed immediately after complete drainage of the hydrothorax, presumably due to relief of the high intrapleural pressure that impeded tracer migration. The pathogenesis of hydrothorax in CAPD remains unclear. Leakage via diaphragmatic lymphatics, thoracic duct or through congenital or acquired defects or blebs with a one-way valve mechanism in the diaphragm have all been implicated [8 12]. The fact that anatomic defects are more commonly situated in the right hemidiaphragm may account for the preponderance of rightsided hydrothorax in most series, including ours. Regardless of the underlying abnormality, the physiologic negative intrapleural pressure and the positive intraperitoneal pressure in CAPD act in concert to promote the transfer of dialysate from the abdominal to the pleural cavity, if a physiologic weak point exists. The clinical consequence of hemi-hydrothorax has once been considered an indication for permanent cessation of CAPD and transfer to haemodialysis [13,14]. Various manoeuvres of pleurodesis have been reported in the treatment of this condition, including mechanical rub pleurodesis [5,15], and chemical pleurodesis using tetracycline, fibrin glue, steroid, nocardia rubra cell wall skeleton, OK-432 (haemolytic streptococcal derivatives) and autologous blood [1,13,16,17]. Whatever the treatment used, the desired pleural adhesion was not always firmly formed, resulting in frequent recurrence of hydrothorax [1,3,18 20]. Thoracoscopy-guided identification and direct obliteration of pleuroperitoneal communication [9,12] has been reported as another mode of treatment. However, most diaphragmatic defects are indeed microscopic and difficult to localize, even at autopsy [18,21]. To date, there is no consensus concerning the most effective therapeutic approach to CAPD-related hydrothorax. We chose talc poudrage for three reasons. First, talc is the most effective sclerosant agent to date and is extensively used to treat malignant pleural effusions, with reported success rates of 87 93% [22,23]. Here, we showed that after a follow-up of 18.8 months, 89% of patients did not develop recurrence while being resumed on CAPD. Importantly, there was no compromise in chest outcome in terms of pulmonary function or radiologic appearance. Secondly, mechanical rub pleurodesis may be associated with more bleeding complications, and is undesirable in the uraemic state. Thirdly, we do not favour direct repair or obliteration of diaphragmatic flaws not only because they are difficult to localize intraoperatively [18,21], but also because the repair of such lesions does not prevent recurrence or the subsequent appearance of new defects. To our knowledge, there has been no report in the literature that systematically examined the outcome of VATS talc pleurodesis in the treatment of CAPD-related hydrothorax. Here, we showed that this procedure is well tolerated and effective. All patients were returned to CAPD successfully, except for one recurrence at 7.5 months that was also successfully treated by repeating the procedure.

5 808 S. Tang et al. In conclusion, hydrothorax-complicating CAPD developed in 1.9% of patients in our cohort. Eightynine per cent are right-sided. Assay of simultaneous peritoneal and pleural aspirate protein content is the simplest and cheapest way to suggest this clinical condition. This complication of CAPD does not mandate permanent cessation of peritoneal dialysis and conversion to maintenance haemodialysis. We recommend VATS talc pleurodesis as the therapy of first choice for pleuroperitoneal communication because of its safety, reliability and low recurrence rate. Acknowledgements. This study was supported in part by the Jardine Charity Fund. Conflict of interest statement. None declared. References 1. Nomoto Y, Suga T, Nakajima K et al. Acute hydrothorax in continuous ambulatory peritoneal dialysis a collaborative study of 161 centers. Am J Nephrol 1989; 9: Fine RN, Salusky IB. CAPDuCCPD in children: four years experience. Kidney Int Suppl 1986; 19: S7 S10 3. Jagasia MH, Cole FH, Stegman MH, Deaton P, Kennedy L. Video-assisted talc pleurodesis in the management of pleural effusion secondary to continuous ambulatory peritoneal dialysis: a report of three cases. Am J Kidney Dis 1996; 28: Kanaan N, Pieters T, Jamar F, Goffin E. Hydrothorax complicating continuous ambulatory peritoneal dialysis: successful management with talc pleurodesis under thoracoscopy. Nephrol Dial Transplant 1999; 14: Mak SK, Nyunt K, Wong PN et al. Long-term follow-up of thoracoscopic pleurodesis for hydrothorax complicating peritoneal dialysis. Ann Thorac Surg 2002; 74: Chow KM, Szeto CC, Wong TY, Li PK. Hydrothorax complicating peritoneal dialysis: diagnostic value of glucose concentration in pleural fluid aspirate. Perit Dial Int 2002; 22: Ortiz L, Hazley D, Seikaly MG. Thoracocentesis helps diagnose diaphragmatic defects in peritoneal dialysis patients. Pediatr Nephrol 2001; 16: Okada H, Ryuzaki M, Kotaki S et al. Thoracoscopic surgery and pleurodesis for pleuroperitoneal communication in patients on continuous ambulatory peritoneal dialysis. Am J Kidney Dis 1999; 34: Tsunezuka Y, Hatakeyama S, Iwase T, Watanabe G. Video-assisted thoracoscopic treatment for pleuroperitoneal communication in peritoneal dialysis. Eur J Cardiothorac Surg 2001; 20: Finn R, Jowett EW. Acute hydrothorax complicating peritoneal dialysis. Br Med J 1970; 2: LeVeen HH, Piccone VA, Hutto RB. Management of ascites with hydrothorax. Am J Surg 1984; 148: Di Bisceglie M, Paladini P, Voltolini L et al. Videothoracoscopic obliteration of pleuroperitoneal fistula in continuous peritoneal dialysis. Ann Thorac Surg 1996; 62: Huang JJ, Wu JS, Chi WC, Lan RR, Yang LF, Chiu NT. Hydrothorax in continuous ambulatory peritoneal dialysis: therapeutic implications of Tc-99m MAA peritoneal scintigraphy. Nephrol Dial Transplant 1999; 14: Khanna R. Questions and answers. Perit Dial Bull 1980; 1: Bresticker MA, Oba J, LoCicero J, Greene R. Optimal pleurodesis: a comparison study. Ann Thorac Surg 1993; 55: Simmons LE, Mir AR. A review of management of pleuroperitoneal communication in five CAPD patients. Adv Perit Dial 1989; 5: Benz RL, Schleifer CR. Hydrothorax in continuous ambulatory peritoneal dialysis: successful treatment with intrapleural tetracycline and a review of the literature. Am J Kidney Dis 1985; 5: Allen SM, Matthews HR. Surgical treatment of massive hydrothorax complicating continuous ambulatory peritoneal dialysis. Clin Nephrol 1991; 36: Mak SK, Chan MW, Tai YP et al. Thoracoscopic pleurodesis for massive hydrothorax complicating CAPD. Perit Dial Int 1996; 16: Chao SH, Tsai TJ. Recurrent hydrothorax following repeated pleurodesis using autologous blood. Perit Dial Int 1993; 13: Singh S, Vaidya P, Dale A, Morgan B. Massive hydrothorax complicating continuous ambulatory peritoneal dialysis. Nephron 1983; 34: Walker-Renard PB, Vaughan LM, Sahn SA. Chemical pleurodesis for malignant pleural effusions. Ann Intern Med 1994; 120: Kennedy L, Sahn SA. Talc pleurodesis for the treatment of pneumothorax and pleural effusion. Chest 1994; 106: Received for publication: Accepted in revised form: