Indwelling pleural catheters for benign pleural effusions - Springer Link

Curr Respir Care Rep (2014) 3:61–70 DOI 10.1007/s13665-014-0073-5

PLEURAL DISEASES AND MESOTHELIOMA (G LEE, SECTION EDITOR)

Indwelling pleural catheters for benign pleural effusions O. J. Bintcliffe & D. T. Arnold & N. A. Maskell

Published online: 20 March 2014 # Springer Science+Business Media New York 2014

Abstract Indwelling pleural catheters (IPCs) have an established role in the management of recurrent pleural effusions due to malignancy. They are typically used in patients with trapped lung, those who have previously failed an attempted talc pleurodesis, or as first-line therapy. Experience of, and evidence for, IPC use in this setting is well established. In contrast, IPC use in patients with recurrent pleural effusions due to benign disease is limited, and there are no randomized studies evaluating their efficacy and safety in this patient group. Retrospective data suggest that IPCs may be effective at reducing breathlessness with acceptable complication rates, comparable to those seen in malignant effusions. This paper summarizes the epidemiology, pathophysiology and treatment options for benign pleural effusions, and reviews the published data assessing IPC use in this population.

malignant pleural effusions. Their use has been demonstrated to be safe, cost effective and associated with improvements in dyspnea and quality of life indices [1•]. However, IPC use has been limited in recurrent pleural effusions with a nonmalignant aetiology. In this population, the evidence base is much weaker and is currently limited to observational data. As the prevalence of benign diseases causing recurrent pleural effusions continues to rise, in particular congestive cardiac failure [2] and chronic liver disease due to non-alcoholic fatty liver disease [3], there is an increasing awareness of the possible role of IPCs in this population. Many of the causes of recurrent non-malignant effusions are associated with a poor prognosis, not dissimilar to that seen in some malignant diseases. This review aims to critically evaluate recent literature, as well as to highlight areas of uncertainty that require further research.

Keywords Pleural effusion . Hepatic hydrothorax . Congestive cardiac failure . Pleural infection . Thoracentesis . Pleurodesis . Indwelling pleural catheters

Case vignette

Introduction Over the past decade, an increasing body of evidence has evolved, clearly showing the benefits of indwelling pleural catheter (IPC) placement in patients with symptomatic O. J. Bintcliffe : D. T. Arnold : N. A. Maskell (*) Academic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol, UK e-mail: [email protected] O. J. Bintcliffe e-mail: [email protected] D. T. Arnold e-mail: [email protected]

A sixty-nine-year old man with primary biliary cirrhosis leading to portal hypertension and ascites was referred to our service in October 2013 with a large right-sided pleural effusion and worsening exertional breathlessness. A therapeutic aspiration of 1.5 L of pleural fluid provided a symptomatic improvement and demonstrated a transudate (protein 2 g/dL, LDH 148 IU/L, Glucose 144 mg/dL). Pleural fluid cytology demonstrated 80 % mesothelial cells, no malignant cells were identified, and computerised tomography (CT) demonstrated no evidence of pulmonary embolism or malignancy (see Fig. 1). Despite medical treatment including high dose diuretic therapy, sodium restriction and ursodeoxycholic acid, the patient required repeated therapeutic aspirations at intervals of about 1 week over the subsequent 7 weeks, with a total drainage of 8.7 L. His breathlessness continued despite this

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Curr Respir Care Rep (2014) 3:61–70

Fig. 1 a Chest radiograph at presentation, b CT image at presentation, c Chest radiograph with IPC in place – illustrated by arrows, d Indwelling pleural catheter, e Vacuum Drainage Bottle, f IPC position in a patient

management due to a persistent effusion, and so, following discussion with the patient and his hepatologist, an indwelling pleural catheter was inserted in early December 2013. Concurrently, he was worked up for possible liver transplantation. His IPC is currently being drained on a three times weekly regime, with 4 L removed each week. As would be the case with paracentesis locally, he is given 100 ml of 20 % human albumin solution for each 3 L of fluid drained. He has had no complications from IPC insertion to date and his renal function and serum albumin are stable.

Indwelling pleural catheters Indwelling pleural catheters are multi-fenestrated tubes made from a flexible silicone elastomer that are introduced into the pleural space through a tunnel of subcutaneous tissue. A small polyester cuff at the tube’s midpoint lies within the subcutaneous tissue and anchors it in place. At the proximal end is a one-way valve, which can be attached to a vacuum drainage bottle (see Fig. 1). These tubes can be inserted as a ‘day-case’ procedure, allow outpatient drainage of pleural fluid, and by virtue of their tunnelled section, are held in place without sutures. In 1997, the US Food And Drug Administration (FDA) approved the PleurX catheter for use in drainage of malignant pleural effusions [4]. This license was extended in 2001 to all pleural effusions, regardless of aetiology [5]. Since then, the

use of IPCs in malignant disease has become increasingly widespread. Concurrently, the evidence base for their use in malignant pleural disease has strengthened, demonstrating a safe, outpatient delivered option for persistent pleural effusions, which is cost-effective relative to talc pleurodesis, although this cost effectiveness is influenced by prognosis and duration of use [6, 7]. By contrast, the use of IPCs in benign pleural effusions has been relatively limited. The reasons for this are multifactorial and are likely to be related to the lack of randomized data to support their use, potentially a lack of awareness of this technique amongst the physicians caring for cardiology or hepatology patients with pleural effusions, and concerns over the risk of infection and bleeding. Nevertheless, IPCs have been studied in a variety of non-malignant aetiologies that give rise to recurrent effusions. Below we outline some of these major causes with a focus on prevalence, pathophysiology and treatment options.

Causes of benign pleural effusions Liver cirrhosis Recurrent pleural effusion is a complication in 5 % to 10 % of patients with liver cirrhosis [8, 9], and given the prevalence of cirrhosis, hepatic hydrothorax is one of the most common causes of recurrent non-malignant pleural effusion,


accounting for one-third of cases in some series [10•]. The pathophysiology of pleural fluid accumulation is thought to be due to diaphragmatic defects allowing ascitic fluid to track into the pleural space, with the majority (85 %) affecting the right hemithorax [8]. Radioisotope studies have demonstrated the passage of ascitic fluid from the peritoneal cavity into the pleural cavity with negative intrathoracic pressure facilitating this passage of fluid [11]. Malnutrition in cirrhosis is thought to contribute to this process by increasing the size of diaphragmatic defects due to thinning of diaphragmatic muscle [12]. Medical management of hepatic hydrothorax is the same as for ascites, and includes sodium restriction and diuretic therapy, but in approximately 20 % the hepatic hydrothorax will persist [12]. The persistent presence of a hepatic hydrothorax should prompt consideration for liver transplant [13] or transjugular intrahepatic portosystemic shunt (TIPS) placement [14]. However, availability of liver transplants is limited, and for many patients this is not an option. In patients unable to undergo transplantation, TIPS has been shown to be an effective strategy, but it carries significant risks and failure rates. In a study in which 24 Child-Pugh class B and C cirrhosis patients with hepatic hydrothorax underwent TIPS, the procedure was successful in 14/24 (58 %). However, six patients (25 %) died within 40 days of the procedure, either due to post-procedural complications or liver failure, and nine patients (38 %) developed transient hepatic encephalopathy [15]. Repeated pleural procedures are often required in those patients who are not suitable for TIPS or liver transplant, or for those who need symptomatic relief in the interim. Congestive cardiac failure (CCF) Between 1 % and 2 % of the adult population has heart failure [16], although there is a higher prevalence (7.5 %) in those over the age of 70 years [17]. The majority of patients requiring hospital admission for heart failure have detectable effusions on CT imaging [18]. Pleural fluid accumulates due to elevation of right or left-sided ventricular filling pressures increasing either systemic or pulmonary venous pressure, respectively. This process causes bilateral effusions in about 70 % of cases [19]. Unilateral effusions are usually right sided, although the reason for this propensity is unclear [20]. Firstline treatment for effusions due to CCF includes optimized medical management and may also include specific intervention directed at the cause of heart failure, such as biventricular pacing or percutaneous or surgical valve intervention. Around 90 % of pleural effusions due to heart failure will resolve with treatment of underlying heart failure [18]. However, there remains a significant minority with symptomatic effusions despite optimal management in whom there may be a role for strategies directed specifically towards the pleural effusion.

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Hepatic and cardiac aetiologies account for the majority of benign cases of persistent pleural effusion. There are a number of rarer causes that may be encountered in clinical practice for which IPCs may be considered a useful management strategy. Renal failure In view of the improved survival of patients with end stage renal failure, potential sequelae of both the disease and longterm dialysis are likely to increase in prevalence. Pleural effusion may develop due to systemic hypervolemia, uremic pleuritis and pericarditis, or infection. A retrospective study of 257 hospitalized patients on long-term dialysis found that pleural effusion was present on chest radiographs in 20 %, of which around 70 % were bilateral and the cause was attributed to hypervolemia in the majority of patients (62 %) [21]. The role of pleural procedures in improving the quality of life of these patients may be important, as they are often symptomatic with a pleural effusion despite optimized medical therapy. Additionally, it should be noted that repeated thoracentesis is a considerable risk in such patients, given their propensity to infection and high rates of concurrent anticoagulation, which may prompt consideration of a more definitive approach [21]. Post coronary artery bypass graft Following coronary artery bypass grafting (CABG), the vast majority of patients develop pleural effusions in the immediate postoperative period. A study assessing presence of effusion by ultrasound demonstrated 89 % of patients have an effusion at 1 week, dropping to 57 % at 1 month following CABG [22]. These effusions are normally small and asymptomatic [23]. However, a minority will develop larger effusions requiring drainage. Persistent effusions following CABG, which are often lymphocytic [24], have been postulated to have an immunological cause distinct from the initial effusions, which are commonly blood stained or attributed to post-cardiac injury syndrome [25]. A large prospective study of over 300 patients following CABG found that 10 % had developed a large effusion at 30 days, but that the majority resolved with conservative management; 12.9 % of patients required thoracentesis in the 90 days following surgery [26]. Rates of persistent pleural effusion were low; six of the 30 patients who had a large effusion at 30 days required more than one thoracentesis, and only one patient was still requiring periodic thoracentesis at 1 year [26]. Chylothorax Chylothorax is caused by obstruction of the thoracic duct or its tributaries, resulting in a leakage of chyle into the pleural space. This is often a traumatic or a post-surgical complication, but can also occur secondary to yellow-nail syndrome,

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sarcoidosis, tuberculosis or malignancy, particularly lymphoma [27]. Patients will often require surgery in the form of thoracic duct ligation if they do not respond to conservative management such as a reduced-fat diet, but some patients may be unfit for surgery or have recurrent effusions despite this. Failure of initial management is particularly common in nontraumatic causes of chylothorax. A retrospective study of 74 patients with chylothorax demonstrated that of those with a non-traumatic cause, only 27 % respond to initial management and 32 % fail to resolve after surgical management [28]. Pleural infection Pleural infection is typically managed either with antibiotics and intercostal tube drainage (with or without the use of intrapleural fibrinolytics) or surgery. In a small number of patients, who are unsuitable for surgery, a chronic effusion due to an infected pleural effusion may persist due to a failure of medical management. Two such cases are discussed by Davies et al., in which the use of indwelling pleural catheters achieved satisfactory long-term drainage with good radiological and clinical outcomes [29].

Treatment options for recurrent benign pleural effusions For the major aetiologies of benign pleural effusions, therapy specific to the underlying pathology plays a primary role in prevention of fluid accumulation. Therapeutic pleural aspirations may be necessary to improve patient symptoms whilst management is optimized; however, in some persistent cases, patients’ ongoing symptoms may necessitate pragmatic fluid management strategies, some of which are now discussed. Repeated thoracentesis The first presentation of a unilateral pleural effusion will often prompt thoracentesis as a therapeutic and diagnostic procedure [30]. In many cases, a single procedure may be all that is required; however, patients with refractory and recurrent benign pleural effusions will often require repeated aspirations to control symptoms. If the rate of the accumulation is rapid, then repeated thoracentesis is associated with considerable patient burden due to regular hospital attendances, procedural discomfort and worsening of symptoms in the interval between procedures. There may be considerable healthcare costs associated with brief but repeated hospital attendances. Finally, patients may be anticoagulated, either therapeutically, or as may be the case in patients with liver cirrhosis, secondary to the disease process. Although thoracentesis has been demonstrated to be safe in patients with a bleeding tendency (up to a prothrombin time of twice normal) [31], this risk will increase with multiple procedures. Data from 231 therapeutic aspirations suggest that


complications include pain (7.8 % of procedures), symptomatic hypotension (0.9 %), failure of procedure (2.2 %) and iatrogenic pneumothorax (0.4 %) [32]. Although generally a safe procedure, particularly since the uptake of ultrasound guidance, the risks of repeated procedures, potentially as frequently as every week, should be carefully considered. Chest drain and pleurodesis The use of intercostal tube drainage and pleurodesis in recurrent malignant pleural effusions is well established and recommended by guidelines [33]. A large retrospective study evaluating success of talc pleurodesis in a total of 611 patients demonstrated a success rate of 77 % in the 68 patients with benign disease. However, this study excluded patients requiring more than one pleurodesis attempt, and the distribution of aetiologies of the benign effusions studied is not clear [34]. In addition to this, two smaller retrospective studies have described similar success rates. Glazer et al. reported talc pleurodesis to be successful in 75 % of 16 non-malignant effusions of varying aetiology [35]. Sudduth et al. report a success rate of 80 % with varied pleurodesis agents in 25 effusions with benign aetiologies [36]. Concerns pertaining to the safety of talc have previously been voiced [37, 38], some of which may be particularly relevant in a population with non-malignant effusions, who may have a prognosis significantly better than those with malignant disease. In addition, graded talc is not universally available, and pleurodesis with ungraded talc with small particles (< 10 μM) is associated with greater levels of systemic inflammation and significantly poorer gas exchange than graded talc in which these small particles are removed [39]. Regardless of aetiology, intercostal tube placement and pleurodesis for patients with a pleural effusion leads to a potentially prolonged hospital admission. Intercostal tube placement and talc pleurodesis in patients with hepatic hydrothorax may be associated with high periprocedure mortality, reported at 45.5 % in a small case series [40]. The use of pleurodesis in unilateral pleural effusions due to CCF has been previously discouraged, due to the observation of subsequent development of contralateral effusions [41]. Thoracoscopy and poudrage Thoracoscopy and talc poudrage has been assessed in a number of studies as a treatment option in patients with hepatic hydrothorax. In 18 patients undergoing 21 such procedures, success rates of only 47.6 % were obtained [42]. This study also included diaphragmatic defect closure at thoracoscopy in five cases. High mortality and morbidity rates were demonstrated in this patient group (38.9 % mortality in the 3-month


follow-up period), and patients required long inpatient hospital stays (mean 15 days). A further study on 15 patients with hepatic hydrothorax demonstrated success rates of 53 % after a mean follow-up period of 5 months after initial videoassisted thoracic surgery (VATS) and pleurodesis [43]. Indwelling pleural catheters A number of studies have investigated the efficacy, safety and costs of IPCs in malignant disease. However, in patients with recurrent pleural effusions with a benign aetiology, evidence is more limited. We have carried out a review of literature surrounding the use of IPCs in benign disease with a focus on outcomes, limitations and safety. Our review of current published literature regarding IPCs in benign disease identified nine peer-reviewed studies and six abstracts, the results of which are illustrated in Table 1. A number of studies report case series of specific diseases, so it is impossible to assess the overall relative frequencies of the benign aetiologies that make up the population of nonmalignant effusions presenting to respiratory services. However, the larger published studies of consecutive patients, namely Bhatnagar [10•], Mullon [48] and Parsaei [56], found the major aetiologies to be hepatic hydrothorax, congestive cardiac failure and post cardiac surgery, respectively. Outcomes of IPCs in benign disease In both benign and malignant disease, the primary role of an IPC is to alleviate the symptoms of recurrent effusions without the need for regular hospital attendances or additional procedures. The focus of outcomes should therefore be: improvement of symptoms, quality of life, and freedom from repeated intervention or hospitalization. The majority of studies where symptoms were recorded noted an improvement in symptoms with IPC insertion. Srour et al. studied 38 patients with cardiogenic pleural effusions and assessed symptom improvement using a dyspnea index, noting a ‘significant improvement in dyspnea 2 weeks after IPC insertion’ [45•]. Although only a small number of patients (n=5) were assessed in the study by Herlihy et al., there was a notable improvement in patients’ function: all patients moved from New York Heart Association class 4 to 2 [54]. Mullon et al. studied 109 patients with a variety of benign effusions, and 96 % of patients reported improvement in symptoms after IPC insertion [48]. They also assessed the number of hospitalizations from pleural disease 1 year before and after IPC insertion: IPCs were associated with a reduction in hospitalizations from 1.6 per patient to 0.4 per patient, with the largest reduction seen in CCF effusions [48]. A statistically significant reduction in hospitalizations was also seen in a study by Borgeson et al., in which patients with CCF related effusions

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had a reduction in admissions from 3.5/year before IPC to 1.9/ year subsequently [52]. Chalhoub et al. assessed patient satisfaction with the procedure itself, using a 1 to 4 point questionnaire; the mean satisfaction rating for 23 patients with mostly CCF and hepatic hydrothorax related effusions was 3.8, equivalent to the majority being ‘happy with the procedure’ or ‘would have it again if needed’ [47•]. It appears based on this limited evidence that IPCs improve symptoms and reduce hospitalizations in recurrent benign effusions. Unfortunately, given the relatively small numbers and the grouping of all types of effusions, limited comparisons can be made between outcomes of effusions with different aetiologies. Pleurodesis following IPC insertion in benign disease It has been well documented that IPCs can result in pleurodesis when inserted for malignant pleural effusions, without the use of talc or other pleurodesis agents. This is thought to be due to an inflammatory process initiated by the presence of a foreign body in the pleural space [58]. The proportion of patients with malignant pleural effusions who benefit from this ‘spontaneous’ pleurodesis varies between studies, but collated data suggests an overall rate of around 45 % [59]. The majority of studies in benign disease reported the rate of pleurodesis in their patient group, but these rates varied widely. This is likely a product of small numbers, heterogeneous patient groups, and varying definitions of pleurodesis. A series of 57 patients with heterogeneous benign causes of pleural effusions reported a pleurodesis rate of 33 % [10•]. The study noted that patients with hepatic hydrothorax were less likely to pleurodese and that time to pleurodesis was significantly longer, compared to other aetiologies. However, when analysing a cohort of 14 patients with exclusively hepatic hydrothorax, Schneider et al. reported pleurodesis rates of 71 % at a median of 70 days [55]. The figures for recurrent effusions secondary to CCF are more consistent. Srour et al. studied 38 patients with cardiogenic pleural effusions, in which 11 (29.0 %) successfully pleurodesed after a median of 66 days [45•]. This compares to 44 % at a median 38 days reported by Bhatnagar et al. [10•]. Early complications Despite being used in patients with considerable comorbidity, serious short-term complications resulting from IPC insertion appear to be rare. Literature from both malignant and benign disease reveals just one case of operational mortality directly related to IPC insertion. One patient in a series of 11 patients with a benign chylothorax suffered a fatal pulmonary embolism after replacement of an IPC due to occlusion of the initial IPC [44•].

96 % reported symptom improvement Reduced hospitalization

Schneider (2009) [55]

Borgeson (2009) (Abstract) [52] French (2009) (Abstract) [53] Herlihy (2009) [54]

100 % moved from NYHA index Class 4 to 2 Not assessed

CCF – 5 (100 %)

5

14 (12 patients)

IP – 10 (83 %) HH – 2 (17 %)

Allowed outpatient management

SVC syndrome – 1 (100 %)

1

Not assessed Reduced hospital admissions

12

23

1 14

Mercky (2010) [49] Kilburn (2010) (Abstract) [50] Vakil (2010) [51] Post lung transplant – 12 (100 %) CCF – 23 (100 %)

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Mullon (2011) (Abstract) [48]

Improved dyspnea Not assessed

Empyema – 5 (5 %) Drain occlusion – 4(4 %) Pneumothorax – 2 (2 %) Leakage – 2 (2 %) Pain – 2 (2 %) Malposition – 1 (1 %) Site infection – 1 (1 %) 1/1 (100 %) [180 days] Site infection – 1 (100 %) 9/14 (62.5 %) [timing not noted] Empyema – 2 (14 %)

Patient satisfaction high (3.8/4.0)

CCF – 13 (57 %) HH – 8 (35 %) Traumatic – 1 (4 %) Idiopathic – 1 (4 %) CCF – 44 (40 %) IP – 26 (24 %) Chylothorax – 10 (9 %) RF – 6 (6 %) HH – 5 (5 %) Trapped lung – 5 (5 %) Other – 13 (12 %) HH – 1 (100 %) HH – 14 (100 %)

23

10/14 (71 %) [89 days]

0%

0%

11/12 (91.6 %) [ 86 days] 9/23 (39 %) [109 days]

64/109 (59 %) [90 days]

Not divided by pathology

Empyema – 2 (40 %) Loculation – 1 (20 %) Not divided by pathology

Hemothorax – 1/12 (8 %) Empyema – 1/12 (8 %) Empyema – 2 (16 %) Drain occlusion – 2 (16 %) None

Post –operative pain – 4 (17 %) Site infection – 1 (4 %)

23/23 (100 %) [110 days] Time to pleurodesis shorter in HH


HH – 10 (100 %)

10

Imler (2012) (Abstract) [46] Chalhoub (2011) [47•]

11/43 (29 %) [66 days] Improvement in dyspnea based on a formally assessed symptom questionnaire

CCF – 43 (100 %)

43

Srour (2013) [45•]

9/14 [176 days]


40 %

100 %

100 %

91.6 %

100 % Not assessed

Not assessed

100 %

100 %

94.6 %

78.5 %

88.7 %

None – 48 (84 %) Empyema – 2 (3.5 %) Site infection – 4 (7 %) Loculation – 4 (7 %) Leakage – 1 (2 %) Pain – 2 (4 %) Transient blockage – 1 (2 %) Acute RF – 2 (4 %) Drain failure – 1 (2 %) Transient blockage – 2 (14 %) Mild reduction of albumin, total protein and/or lymphocyte counts – 3 (21 %) Symptomatic loculation – 2 (4.7 %) Moderate/Large pneumothorax – 5 (11.6 %) Leakage – 1 (2.3 %) Not divided by pathology

Not assessed

14

DePew (2013) [44•]

19/57 (33 %) [71 days] HH were much less likely to pleurodese

Chylothorax – 14 (100 %)

57

Bhatnagar (2013) [10•]

Not assessed

Freedom from further pleural procedures

Complications (%)

HH – 19 (33 %) IP – 15 (26 %) Empyema – 9 (16 %) CCF – 9 (16 %) YNS – 3 (5 %) Chylothorax – 2 (4 %)

Pleurodesis achieved? (%) [Time – median]

Patient outcomes

No. of IPCs for benign effusions

Primary Author (year)

Effusion Aetiology by no. of patients (%)

Table 1 Published studies of the use of IPC in benign effusions

66 Curr Respir Care Rep (2014) 3:61–70

45 (42 patients)

11

382 (377 patients)

Parsaei (2006) (Abstract) [56]

Murthy (2006) [57]

TOTALS

26/45 (58 %) [timing not noted]


Not assessed


Cardiac surgery – 11 (26 %) CCF – 9 (21 %) IP – 6 (14 %) RF – 4 (10 %) HH – 3 (7 %) Idiopathic – 9 (21 %) CCF – 3 (27 %) HH – 2 (18 %) Other – 6 (55 %) CCF – 149 (40 %) HH – 64 (17 %) IP – 57 (15 %) Chylothorax – 26 (7 %) Post surgery – 23 (6 %) Idiopathic – 10 (3 %) RF – 10 (3 %) Empyema – 9 (2 %) Trapped lung – 5 (1 %) YNS – 3 (1 %) Other – 21 (6 %)

Pleurodesis achieved? (%) [Time – median]

Patient outcomes

Effusion Aetiology by no. of patients (%)

Empyema – 18 (5.2 %) Site infection – 10 (2.9 %) Pain – 8 (2.3 %) Loculation – 7 (2.0 %) Significant pneumothorax – 7 (2.0 %) Drain occlusion – 6 (1.7 %) Bleeding – 3 (0.9 %) Leakage – 4 (1.2 %) Fluid shift – 5 (1.4 %) Of 347 with data available


87 %

Empyema –4 (9 %) Site infection – 3 (7 %) Bleeding – 2 (4 %)


Freedom from further pleural procedures

Complications (%)

CCF Congestive cardiac failure; IP Inflammatory pleuritis; HH Hepatic hydrothorax; NYHA New York Heart Association; RF Renal failure; SVC Superior Vena Cava; YNS Yellow nail syndrome

No. of IPCs for benign effusions

Primary Author (year)

Table 1 (continued)

Curr Respir Care Rep (2014) 3:61–70 67

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Postoperative pain following the procedure can usually be managed with simple analgesics, but a small minority of IPCs are removed as a result [60] . Bleeding is a risk of IPC insertion that is especially relevant to anticoagulated patients. There is little guidance in published literature on platelet or INR (international normalized ratio) thresholds for IPC insertion, or on recommendations for stopping antiplatelet therapy. However, documented cases of intra or postoperative bleeding are rare. From our review, only Parsaei et al. and Vakil et al. noted ‘bleeding’ complications, with a rate of 4 % (2/45) and 8 %, respectively (1/12) [51, 56]. Our standard practice is to check the patient’s clotting screen prior to the procedure, having stopped medications such as warfarin and clopidogrel 1 week prior to IPC insertion and omitted doses of low molecular weight heparin and oral anticoagulants such as dabigatran and rivaroxaban in the 24 hours before the procedure. Late complications Due to the nature of the diseases and the apparent slower rates of pleurodesis, IPCs often remain in-situ for longer periods in patients with benign effusions. Given that these patients are also often relatively immunocompromised, there are concerns of increased rates of pleural infection. The two largest case series reported pleural infection rates of 3.5 % [10•] and 5 % [48], respectively, a similar rate to that reported in malignant disease [61]. Pleural infection, if unresponsive to oral antibiotics, usually warrants hospital admission with intravenous antibiotics and in some cases drain removal, but mortality relating to pleural infection appears to be rare. In a large retrospective review of IPCs in 1,021 patients with malignant disease, mortality related to pleural infection was 0.29 %. In this cohort, one death directly resulted from pleural infection and in a further two patients, infection may have contributed to death caused by progression of cancer [61]. Such large series do not exist in benign disease, but our review of 15 studies on 382 IPC insertions noted only one death, in a 92year-old lady with an effusion related to CCF [54]. Concerns over the increased risk of renal failure, electrolyte disturbance or protein loss are more pertinent in certain benign aetiologies, given the sometimes massive volumes of fluid being drained in patients with an already poor homeostatic reserve. Bhatnagar et al. noted that patients with hepatic hydrothorax drained considerably more fluid than other aetiologies, with a mean output of 5.1 L per week [10•]. In this study, local hepatology services recommended that these patients should receive 20 % Human Albumin solution to counteract protein loss. Across the entire cohort, acute renal failure occurred in 4 % of patients. Due to the lipid-rich fluid produced in chylothoraces, some literature cautions against regular drainage [62]. However, DePew et al. specifically investigated the effect of serial effusion drainage by IPCs on serum


albumin, total protein, leukocytes and lymphocytes in 12 patients with benign chylothorax. Although mild reductions in the above were documented in three patients, they were not thought to be clinically significant, and “no significant adverse nutritional, hemodynamic or immunologic outcomes were reported during follow-up” [44•]. Additionally, a casecontrol study of 19 patients with recurrent symptomatic chylothorax due to a malignant aetiology that included ten patients treated with IPC demonstrated a fall in albumin levels, but this was not worse that the decline seen in the control group, which was treated predominantly with repeated therapeutic thoracentesis [63].

Conclusions Given the limited and retrospective evidence, it is difficult to make firm assertions as to the current role of IPCs in benign disease. Where reported, studies show high levels of patient satisfaction with the procedure and an improvement of symptoms in the majority. As with malignant disease, complication rates, both early and late, appear reasonably low. There also seems to be no significantly increased rates of pleural infection over that seen with IPC use in malignant effusions. However, if pleural procedures are required for benign disease, then this should only be after optimization of therapies targeting the underlying pathology. Therefore, patients considered for an IPC should have had optimization of medical therapy and have been considered for surgical intervention where possible. It follows that these patients typically have a poor life expectancy, and our emphasis should be on preserving quality of life and independence whilst minimizing symptoms. IPCs offer patients an outpatient delivered therapy for effusion drainage, which may be preferable to repeated hospital attendances for therapeutic aspirations or a potentially prolonged admission for pleurodesis. If the potential drawbacks are acceptable to the patient following discussion with their physician, there may prove to be a place for IPCs in this challenging patient group.

Areas for further research There are numerous unanswered questions relating to IPC use in non-malignant disease. The authors present four important questions. (1) Are IPCs associated with improved quality of life and breathlessness when compared with repeated therapeutic aspirations in a large-scale randomized controlled trial? (2) What is the complication rate associated with IPC use in this population when compared prospectively with standard care?


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(3) Do some specific aetiologies of benign pleural effusion respond better to IPC insertion than others? (4) Is there a requirement for Human Albumin Solution in the regular drainage of hepatic hydrothoraces to reduce the risk of acute kidney injury?

11.

Compliance with Ethics Guidelines

14.

Conflicts of Interest Nick Maskell reports receiving honoraria for sitting on a CareFusion advisory board, and an unrestricted research grant for IPC-Plus Study. Oliver Bintcliffe and David Arnold report no conflicts of interest.

15.

12.

13.

Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

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References

18.

Papers of particular interest, published recently, have been highlighted as: • Of importance

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