Malignant pleural effusions: treatment with tunneled long-term drainage catheters Jeffrey S. Pollak, MD

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1 Malignant pleural effusions: treatment with tunneled long-term drainage catheters Jeffrey S. Pollak, MD Malignant pleural effusion is a significant cause of morbidity and a poor prognostic indicator. Traditional treatments have variable success and significant drawbacks, including a length of stay in the hospital. Alternatively, a tunneled pleural catheter permits long-term drainage as an outpatient, cost-effectively controlling the effusion and related symptoms in over 80 to 90% of patients. Other advantages are the ability to treat trapped lungs and large locules. Spontaneous pleurodesis may occur in over 40% of patients, and the catheter can be used to administer sclerosant or antineoplastic agents. Complications tend to be minor and easily managed. A tunneled pleural catheter should be considered for all patients with MPE having a reasonable expectancy of being an outpatient. Curr Opin Pulm Med 2002, 8: Lippincott Williams & Wilkins, Inc. Section of Vascular and Interventional Radiology, Department of Radiology, Yale University School of Medicine, New Haven, Connecticut, USA. Correspondence to Jeffrey S. Pollak, MD, Section of Vascular and Interventional Radiology, Department of Radiology, Yale University School of Medicine, P.O. Box , New Haven, CT , USA; pollak@biomed.med.yale.edu Current Opinion in Pulmonary Medicine 2002, 8: Abbreviations MPE malignant pleural effusion ISSN Lippincott Williams & Wilkins, Inc. 302 Malignant pleural effusion (MPE) is a common clinical problem, with an estimated annual incidence in the United States of over 150,000 [1]. Almost half of patients with disseminated cancer will develop this problem sometime during their course [2,3]. The etiology is lung or breast cancer in over 50%, lymphoma, ovarian cancer, or gastrointestinal cancer in 25%, and mesothelioma or cancers with no identifiable primary accounting for most of the rest. Thoracic symptoms are present in three-quarters of patients with MPE, with dyspnea on exertion being most common, followed by cough and chest discomfort [1,2,4]. The 30-day mortality is 29 to 50% and the median survival is 3 to 12 months, with lymphoma and breast cancer patients tending toward the longer survival times [2,3]. Given these considerations, the management of MPE is generally palliative, with the goals of prompt relief of symptoms, minimal discomfort, minimal disruption of the patient s everyday life, and cost-effectiveness. Minimizing time in the hospital is often an important factor in achieving these goals. Unfortunately, current regimens for managing MPE have variable success, can be uncomfortable, and may result in a relatively significant number of the patient s remaining days being spent in the hospital. Treatment options for malignant pleural effusion Systemic therapy may be effective in controlling effusions in some patients with lymphoma, small-cell lung cancer, and germ-cell tumors, but locally directed therapy is usually needed in the symptomatic patient. The simplest option of thoracentesis is a valuable diagnostic maneuver, both in determining the etiology and assessing symptomatic improvement. Unfortunately, fluid will reaccumulate in almost all patients [2]. Repeated thoracentesis carries increased risks of pneumothorax, infection, and loculation; therefore, this treatment is typically limited to patients who are expected to respond to systemic therapy or those with a very short life expectancy. The most common treatment is tube thoracostomy and instillation of a sclerosing agent after the lung has reexpanded to induce chemical pleurodesis. Frequently used agents are tetracycline class compounds, bleomycin, and talc slurry. Several randomized trials have found no difference between these three, although talc is often

2 Tunneled pleural catheter for malignant effusions Pollak 303 still recommended based on its lower cost [5 7]. While one randomized study showed thoracoscopic insufflation of aerosolized talc to be superior to bleomycin instillation, another randomized study comparing talc poudrage to talc slurry showed no difference between these two [8,9]. Interestingly, two studies reported pleurodesis rates of up to 43 to 77% with just tube thoracostomy and short-term continuous drainage [10,11]. Side effects of chemical sclerotherapy are primarily pain and fever. Additional major complications reported with talc are respiratory distress, including adult respiratory distress syndrome, and hypotension, with incidences as high as 21 to 33% [12,13]. This includes doses below 10 g, which had been suggested as a threshold value for the occurrence of these more serious complications. Other limitations of chemical sclerotherapy are the discomfort related to traditional large surgical chest tubes, the need for a hospital stay averaging nearly one week, ineffective management of pleural effusions where the lung is trapped and does not completely expand, and the ineffective management of patients with high daily outputs contraindicating sclerotherapy or who fail attempts at sclerotherapy (including large symptomatic residual locules). In order to address the first two concerns, reports have appeared on the use of smaller chest tubes and ambulatory, outpatient management with such tubes for short durations prior to sclerotherapy [14 19]. Pleuroperitoneal shunts and pleurectomy are generally reserved for persistent or recurrent MPEs. The former is limited by the need for frequent pumping of the shunt and occlusion in as many as 25% [20]. Pleurectomy is a major surgical procedure with a complication rate of 23% [21]. Another alternative for managing MPE is a long-term drain in the pleural space. This permits outpatient management of the effusion, relieving associated symptoms regardless of whether pleurodesis occurs. Early experience with long-term pleural drainage Early reports using long-term pleural drains for MPE were encouraging, even after other treatment failures. In 1986, Leff et al. [22] reported the use of a Tenckhoff catheter connected to a subcutaneously implanted access port in a single patient. This was accessed for drainage twice a week to relieve dyspnea. A year later, Hewitt and Janssen [23] described the use of a standard chest tube or Foley catheter connected to a collection system such as a urinary drainage bag, generally with an intervening Heimlich valve to permit only egress from the pleural space. Significant cost savings were proposed when compared to repeated thoracenteses or short-term standard thoracostomy. One drawback of this nontunneled catheter system is the risk of catheter dislodgment. Two subsequent reports noted the value of tunneled Tenckhoff catheters with externalized proximal ends that could be drained by patients or visiting nurses at home whenever needed to relieve symptoms [24,25]. All 13 patients in these two series had effective palliation of their symptoms, and two of the four in Zeldin s series achieved pleurodesis. None of the 9 patients in Robinson s paper had significant changes in their serum protein or albumin levels. Three developed local infections and all were controlled with oral antibiotics. No catheter displacements occurred. More recent experience with long-term pleural drainage is with the Pleurx (Denver Biomaterials, Inc., Golden, CO), a catheter specifically designed for this purpose. Denver Pleurx system The Denver Pleurx is currently the only tunneled catheter specifically designed for managing pleural effusions and was approved by the United States Food and Drug Administration in 1997 (Fig. 1). It is a 15.5 French silicone catheter that is soft and relatively comfortable for long-term use. It has side holes along its distal 24 cm to permit easy entry of fluid and a proximal polyester cuff to induce fibrosis along the subcutaneous tunnel. This decreases the risk of dislodgment and pericatheter leakage and probably decreases the risk of infection in the pleural space. The proximal end has a valved hub that is closed except when a dilator enters it. This prevents inadvertent leakage of pleural fluid or entry of air. A cap is placed over the hub when the tube is not being used and the exposed proximal end covered by a dressing supplied in the kit. Patients benefiting from this tube should have a freeflowing effusion or large locule and improvement in symptoms after prior thoracentesis. After sterilely prepping the skin and giving local anesthesia, an 18-gauge needle is advanced into the pleural space through an intercostal space slightly above the diaphragm. A lateral approach with the needle directed slightly posterior aids in eventually positioning the tube in the posterior costophrenic sulcus for free flowing effusions. The puncture site can be determined most precisely using ultrasound guidance, especially for a loculated collection. The catheter is then subcutaneously tunneled to this entry site from a location 5 to 8 cm anteroinferiorly. The needle is exchanged over a wire for a 16-gauge French peel-away sheath, through which the catheter is placed. The pleural entry incision is stitched closed and the catheter secured at the exit site with a suture. A chest x-ray is obtained to assess catheter position, residual fluid, possible pneumothorax, and the status of the underlying lung. A small pneumothorax is occasionally seen due to entry of air through the peel-away sheath. When first placed, the effusion can be drained using a tube that connects to wall suction. It is recommended

3 304 Diseases of the pleura Figure 1. The Denver Pleurx catheter that no more than 1500 ml of fluid be removed. Subsequent drainages are performed using a special vacuum bottle system. The bottle has a preconnected tube containing a dilator at its free end and a clamp along its shaft (Fig. 2). Drainage should be performed at least every other day, but can be done more frequently. A typical drainage takes no more than 15 minutes and is readily accomplished by a visiting nurse, family members, or the patient. As the bottle s capacity is only 600 ml (and may lose adequate suction after 500 ml), patients with large effusions will occasionally require more than one. No more than 1000 ml of fluid should be drained every 8 hours. Chest pain is common during the first several times complete drainage occurs, as the pleural layers reappose against the catheter, but this then generally abates. If the patient has three drainages that are scant and imaging shows no fluid reaccumulation, the Pleurx is removed as spontaneous pleurodesis has occurred. If necessary, a tube exists permitting connection of the Pleurx to a water-seal suction system. Experience with the Pleurx The results of the randomized investigational trial leading to approval of the Pleurx by the FDA were reported in 1999 [26]. Two-thirds of 144 patients received the Pleurx and one-third were treated with conventional doxycycline sclerotherapy through a chest tube. Equivalent safety and efficacy were shown and there was no difference in median survival. The Pleurx group had a trend toward greater improvement in dyspnea after exercise at 1 to 3 months but similar improvements were seen in quality of life. The median hospitalization time was 1 day for Pleurx patients, the minimum mandated by the study design. The sclerotherapy group had a significantly longer median hospitalization time of 6.5 days. Spontaneous pleurodesis developed in 46% of Pleurx patients (median 29 days, range 8 to 223 days), while pleurodesis occurred in 54% of sclerotherapy patients. A lower amount of fluid drained in the first week correlated with a greater chance for spontaneous pleurodesis. Late recurrence of an uncontrolled effusion occurred in 13% of Pleurx patients. Causes included separate undrained locules developing in seven, catheter occlusion in two, recurrent effusion after pleurodesis in two, and unknown in one. Some of these were managed with catheter replacement or repositioning. Late recurrence occurred in 21% of sclerotherapy patients, which was not significantly different. The severity of pain was similar between the two groups, as was the 10 to 14% rate of early, in-hospital complications. Late complications occurring with the Pleurx were mostly minor and either easily treated or of little consequence to the patient s overall condition. Local cellulitis responding to antibiotics occurred in 6, tumor seeding of the catheter track in 3, catheter obstruction in 2 (replaced in 1), and pleural infection in 1: the only incident requiring hospitalization. In 2000, Putnam et al. [27] looked more closely at the ability of the Pleurx to cost-effectively manage patients with MPE outside the hospital. Of 100 patients treated

4 Tunneled pleural catheter for malignant effusions Pollak 305 Figure 2. Pleurx vacuum bottle drainage system The preconnected tube has a firm dilator at its e nd to enter the hub of the Pleurx catheter. with the Pleurx, 60 outpatients and 40 previously admitted inpatients, 81% had relief of dyspnea and were able to function outside of the hospital environment. This was despite the fact that pleurodesis occurred in only 21%, with no difference between inpatients and outpatients. Significantly lower early, first-week hospital charges were found for patients receiving a Pleurx as an outpatient as compared to either those receiving it as an inpatient or a cohort of 68 patients treated with chest tube and sclerotherapy. The initial outpatient group also showed a trend toward lower long-term charges over the remainder of the patient s life or medical follow-up. Survival was similar in all three groups, although the outpatient Pleurx group tended to live the longest perhaps due to a higher initial performance status. One or more adverse events occurred in 19% of Pleurx patients: recurrent fluid accumulation in 8 generally due to growing loculations, catheter malfunction in 8, and pleural infection in 5. A small series was also reported by Smart and Tung in 2000 [28]. All three patients experienced improvement in dyspnea and no complications occurred. Pleurodesis appeared to occur in at least one patient and probably a second. In early 2001, Pollak et al. [29] reported on their experience in 28 patients, treating 31 hemithoraces. This included 9 patients that were also part of the initial Pleurx trial summarized above. Dyspnea improved in 94% and remained improved in 91% at 30 days. The MPE was controlled in 90% of pleural spaces, including 42% achieving pleurodesis. Of note, pleurodesis occurred in both spaces that were failures of prior chemical sclerotherapy, one of which was one of two patients with symptomatic locules (control of the effusion was achieved in the other locule). Reasons for not controlling the effusion were an initially unrealized multiloculated effusion, the development of a multiloculated effusion, and a growing residual locule in one patient in whom a second catheter could not be placed due to restrictions of the investigative trial. Only 1 patient developed a recurrent effusion 10 months after successful pleurodesis. While only 33% were actually treated as outpatients, in only 7% was hospital time deemed necessary due to care for the catheter. Catheter-related discomfort was not uncommon, especially with complete drainage, but this persisted beyond the first week in only four patients. Adverse events occurred in 21%, which were all minor and readily managed. Four patients had catheters removed and new ones placed for poor drainage, one had external catheter migration necessitating exchange and also developed tumor tracking along the catheter route, and the last patient had a positive pleural fluid culture

5 306 Diseases of the pleura that probably represented colonization. She was already on antibiotics for other reasons and, as she had coincidentally achieved pleurodesis, her catheter was removed. The most recent report on the Pleurx concerns its use in 11 patients (12 hemithoraces) with trapped lung, which is generally considered a contraindication to chemical sclerotherapy [30]. Ten patients (91%) had symptomatic benefit, although none developed pleurodesis. Nine were treated as outpatients. Six complications occurred in 5 patients but these were generally minor and easily treated. The catheter occluded in one patient who also developed loculation. A second catheter was placed in a large locule and the first one removed, but it ruptured and a fragment remained in the pleura. Two other patients developed localized skin breakdown and cellulitis that responded to wound care and antibiotics, and two had positive pleural fluid cultures, at least one of which was felt to represent colonization. Conclusion The experience with drainage of MPE using a tunneled pleural catheter is still not large but appears to be quite promising. Advantages include cost-effective outpatient control of the effusion and its symptoms in over 80 to 90%, a soft silicone catheter that is well tolerated by patients for even months, a fibrotic barrier induced by the cuff that retards dislodgment, intermittent rather than continuous drainage, and treatment of large locules and trapped lungs, which are difficult to otherwise manage. Pleurodesis may occur in over 40%, usually within 1 month, and chemical sclerotherapy can be administered through the catheter, as an outpatient, to potentially increase pleurodesis rates and speed removal of the catheter. Alternatively, the catheter can be used to administer intrapleural anticancer agents. Complications tend to be minor and generally do not significantly affect the patient s overall state. While inadequate drainage by the catheter may eventually occur in as many as 16% of patients (due to occlusion or fibrotic separation from remaining fluid), this is usually easily managed by a new catheter placed in the outpatient setting. In fact, the major limitation is a complex multiloculated effusion, which is a problem for any treatment modality. When considering all these factors, a tunneled pleural catheter becomes an attractive first line treatment for most patients with MPE who have a reasonable expectancy of being an outpatient. References and recommended readings Papers of particular interest, published within the annual period of review, have been highlighted as: Of special interest Of outstanding interest 1 American Thoracic Society. Management of malignant pleural effusions. American Journal of Respiratory & Critical Care Medicine 2000, 162: Grossi F, Pennucci MC, Tixi L, et al.: Management of malignant pleural effusions. Drugs 1998, 55: Tattersall M: Management of malignant pleural effusion. Aust N Z J Med 1998, 28: Sahn SA: Malignancy metastatic to the pleura. Clin Chest Med 1998, 19: Zimmer PW, Hill M, Casey K, et al.: Prospective randomized trial of talc slurry vs bleomycin in pleurodesis for symptomatic malignant pleural effusions. Chest 1997, 112: Twenty-nine patients had 14 treatments with bleomycin and 19 with talc slurry. No significant difference was found in the degree of improvement in pain and dyspnea or in permanent control of effusions, achieved with bleomycin in 79% and with talc in 90%. Talc was recommended as the agent of choice due to its cost advantage. 6 Patz EF Jr, McAdams HP, Erasmus JJ, et al.: Sclerotherapy for malignant pleural effusions: a prospective randomized trial of bleomycin vs doxycycline with small-bore catheter drainage. Chest 1998, 113: No significant difference was found in 30-day response rates between doxycycline and bleomycin. 7 Ong KC, Indumathi V, Raghuram J, et al.: A comparative study of pleurodesis using talc slurry and bleomycin in the management of malignant pleural effusions. Respirology 2000, 5: Early recurrence of malignant pleural effusion was prevented in 89% in the talc slurry group and 70% in the bleomycin group. While the difference was not significant, talc was recommended as it could result in significant cost savings. 8 Diacon AH, Wyser C, Bolliger CT, et al.: Prospective randomized comparison of thoracoscopic talc poudrage under local anesthesia versus bleomycin instillation for pleurodesis in malignant pleural effusions. American Journal of Respiratory & Critical Care Medicine 2000, 162: Thoracoscopic talc poudrage was found to be superior based on lower effusion recurrence rates at 30, 90, and 180 days, with the latter two time points being statistically significant. Cost estimation also favored talc, both for the initial hospitalization and with regard to recurrences. No major adverse effect was seen with either. 9 Yim AP, Chan AT, Lee TW, et al.: Thoracoscopic talc insufflation versus talc slurry for symptomatic malignant pleural effusion [see comments]. Ann Thorac Surg 1996, 62: No statistically significant difference was found between 57 patients randomized to either video-assisted thoracoscopic talc insufflation under general anesthesia (n = 28) or talc slurry by the bedside (n = 29) with respect to chest drainage duration, postprocedural hospital stay, parenteral narcotics requirement, complications, or procedure failure (ie, recurrence). 10 Izbicki R, Weyhing BTD, Baker L, et al.: Pleural effusion in cancer patients. A prospective randomized study of pleural drainage with the addition of radioactive phsophorous to the pleural space vs. pleural drainage alone. Cancer 1975, 36: Groth G, Gatzemeier U, Haussingen K, et al.: Intrapleural palliative treatment of malignant pleural effusions with mitoxantrone versus placebo (pleural tube alone). Ann Oncol 1991, 2: Rehse DH, Aye RW, Florence MG: Respiratory failure following talc pleurodesis. Am J Surg 1999, 177: Brant A, Eaton T: Serious complications with talc slurry pleurodesis. Respirology 2001, 6: A retrospective review of 29 patients having 33 talc pleurodeses showed complications in 52%. Major complications occurred in 24%, consisting of hypoxemia and hypotension. Two patients died. The talc dose was no more than 10 g, and usually less than 5 g. 14 Patz EF Jr, McAdams HP, Goodman PC, et al.: Ambulatory sclerotherapy for malignant pleural effusions. Radiology 1996, 199: Belani CP, Pajeau TS, Bennett CL: Treating malignant pleural effusions cost consciously. Chest 1998, 113: Chen YM, Shih JF, Yang KY, et al.: Usefulness of pig-tail catheter for palliative drainage of malignant pleural effusions in cancer patients. Supportive Care in Cancer 2000, 8: Saffran L, Ost DE, Fein AM, et al.: Outpatient pleurodesis of malignant pleural effusions using a small-bore pigtail catheter. Chest 2000, 118: Sahin U, Mehmet U, Akkaya A, et al.: The value of small-bore catheter thoracostomy in the treatment of malignant pleural effusions. Respiration 2001, 68: Parulekar W, Di Primio G, Matzinger F, et al.: Use of small-bore vs large-bore chest tubes for treatment of malignant pleural effusions. Chest 2001, 120: Lee KA, Harvey JC, Reich H, et al.: Management of malignant pleural effusions with pleuroperitoneal shunting. J Am Coll Surg 1994, 178:

6 Tunneled pleural catheter for malignant effusions Pollak Martini N, Bains MS, Beattie EJ Jr: Indications for pleurectomy in malignant effusion. Cancer 1975, 35: Leff RS, Eisenberg B, Baisden CE, et al.: Drainage of recurrent pleural effusion via an implanted port and intrapleural catheter. Ann Intern Med 1986, 104: Hewitt JB, Janssen WR: A management strategy for malignancy-induced pleural effusion: long-term thoracostomy drainage. Oncol Nurs Forum 1987, 14: Zeldin DC, Rodriguez RM, Glassford DM, et al.: Management of refractory MPEs with a chronic indwelling pleural catheter. Chest 1991, 100: Robinson RD, Fullerton DA, Albert JD, et al.: Use of pleural Tenckhoff catheter to palliate malignant pleural effusion. Ann Thorac Surg 1994, 57: Putnam JB Jr, Light RW, Rodriguez RM, et al.: A randomized comparison of indwelling pleural catheter and doxycycline pleurodesis in the management of malignant pleural effusions. Cancer 1999, 86: This reviews a randomized trial comparing tunneled long-term pleural catheter drainage and doxycyline sclerotherapy. There were comparable levels of symptomatic improvement as well as late recurrence, survival, and adverse events. Hospital time was significantly lower in those treated with the catheter. 27 Putnam JB Jr, Walsh GL, Swisher SG, et al.: Outpatient management of malignant pleural effusion by a chronic indwelling pleural catheter. Annals of Thoracic Surgery 2000, 69: Smart JM, Tung KT: Initial experiences with a long-term indwelling tunneled pleural catheter for the management of malignant pleural effusion. Clinical Radiology 2000, 55: Pollak JS, Burdge CM, Rosenblatt M, et al.: Treatment of malignant pleural effusions with tunneled long-term drainage catheters. Journal of Vascular & Interventional Radiology 2001, 12: Pien GW, Gant MJ, Washam CL, et al.: Use of an implantable pleural catheter for trapped lung syndrome in patients with malignant pleural effusion. Chest 2001, 119: This study looked at the use of tunneled pleural drains in 11 patients with symptomatic, refractory malignant pleural effusions and underlying trapped lungs. This is important since trapped lung syndrome is difficult to manage. Symptomatic benefit occurred in 91% of patients.