Canadian Respiratory Conference 2019

Management of Benign Pleural Effusions with Chronic Indwelling Catheters

April 12th / 2019 Kayvan Amjadi MD, FRCPC Director, Interventional Pulmonology Financial Interest Disclosure (over the past 24 months) Kayvan Amjadi

Company Speaker Advisory Research pfm Medical √ CareFusion √ Objectives

❖ Discuss various management options for the most common refractory and benign causes of

❖ Discuss the potential role for Tunneled Pleural Catheters (TPCs) in patients with refractory and symptomatic non-malignant pleural effusion

❖ Provide some clinical scenarios and highlight specific issues regarding management of benign pleural effusion Annual Incidence of Various Pleural Effusions In the US

Type Incidence (# persons) CHF 500,000 Parapneumonic 300,000 Malignant 200,000 Lung 60,000 Breast 50,000 Lymphoma 40,000 PE 150,000 Viral disease 100,000 () 50,000 Post CABG 50,000 GI disease 25,000 TB 2,500 Mesothelioma 2,300 Asbestos exposure 2,000 Refractory Benign Pleural effusion: Poor Prognosis

• Walker SP et al. Chest 2016; 151:1099 – 1105 – 356 patients, prospectively collected data

– 1-year mortality • Cardiac 50% • Renal 46% • Hepatic 25%

• Bilateral effusions 57% • Transudative effusions 43% Primary Goals of Management

• Emphasize on – “treating the underlying condition”

• Alleviate symptoms in refractory conditions Refractory non-malignant pleural effusion

❖ Vast majority are due to ▪ Cardiac ▪ Hepatic ▪ Renal

❖ Others are secondary to ▪ Trapped lung o Parapneumonic (post therapy of an inflammatory process) o TB o Cardiac injury o PE ▪ BAPE ▪ Connective tissue disorder ▪ Central vein occlusion ▪ Non-malignant Refractory Benign Pleural Effusion

❖ Management of non-malignant pleural effusion can be complicated

❖ Limited literature to guide clinicians

▪ Retrospective data

▪ Conflicting “Expert” opinions

o Controversy ▪ Chylothorax ▪ Hepatic hydrothorax ▪ Cardiac pleural effusion

❖ Life expectancy is variable Treatment Options

• Symptomatic management • Thoracentesis • Chest tube drainage • TIPS • Transplant

• Chemical • Chronic Indwelling Catheters

• Pleuroperitoneal shunt • Pleurectomy Treatment Options

• Symptomatic management • Thoracentesis • Chest tube drainage • TIPS • Transplant

• Chemical pleurodesis • Chronic Indwelling Catheters

• Pleuroperitoneal shunt • Pleurectomy Refractory Cardiac Pleural Effusion Refractory Cardiac Pleural Effusion

❖ 41 y.o. Female with significant past medical history of ▪ Double outlet right ventricle with multiple VSDs, pulmonary valve stenosis and ASD

▪ Classic Blalock-Taussig shunt on left side (age 2)

▪ Fontan procedure 1985 (age 12)

▪ Develops refractory R sided transudative pleural effusion secondary to elevated PA pressures in a failing Fontan o Multiple admissions o Plans were in place for surgical correction Catheter was inserted 8/11/2007 Refractory Cardiac Pleural Effusion

❖ Fontan conversion surgery performed in August 2009

❖ Catheter removed 1/12/2009 ▪ Total of 753 days of drainage o No electrolyte or protein deficiencies

❖ Patient still alive with no recurrence of the effusion

❖ Complication ▪ Required a re-insertion o 1st catheter removed after 571 days due to a leaky valve Management of Refractory Cardiac Pleural Effusion

❖ Diuresis ❖ Afterload reduction ❖ Inotropes ❖ Dietary fluid and salt restriction

❖ Thoracentesis Refractory Cardiac Pleural Effusion and Pleurodesis

❖ Pleurodesis ❖ Webb et al. J Thorac Cardiovasc Surg 1992; 103:881 – 886 ❖ Spicer et al. J Irish Med Assoc 1969; 62:177 – 178 ❖ Davidoff et al. Postgrad Med J 1983; 59:330 – 331 ❖ Glazer et al. Chest 2000; 117:1404 – 1409

❖ 12 patients with CHF, 83% success rate ❖ 7 had talc pleurodesis, successful pleurodesis in 7/7 ❖ 5 had other agents, successful pleurodesis in 3/5

▪ Generally suggested as the “last option”

▪ Davidoff et al. Postgrad Med 1983; 59:330 o Patients remain symptomatic despite pleurodesis o Development of increased pedal , ascites, and contralateral pleural effusion Management of Cardiac Pleural Effusion

❖ 63 year old lady with stage IIIB NSCLC diagnosed in 2005

❖ Presents in March 2011 with R>L pleural effusion and profound dyspnea

❖ Extensive investigations identified presence of restrictive pericarditis secondary to radiation

❖ Required bilateral TPCs for dyspnea management ▪ With good response Refractory Cardiac Pleural Effusion

❖ The left catheter was removed 4 months later ▪ “spontaneous Pleurodesis” ▪ Increased right sided output

❖ Patient requested Pleurodesis of the right side

❖ Thoracoscopic talc poudrage was performed ▪ Had significant decline in respiratory status needing NIV ▪ Developed hepatic congestion and ascites ▪ Had “partial” pleurodesis with ultimate removal of the catheter ▪ No change clinically/radiographically at 3/12 Cardiac Pleural Effusion and Indwelling Catheters

❖ Herlihy et al. TexHeart Inst J 2009; 36:38 ▪ 5 patients with CHF ▪ Catheters remained in place from 1 – 15 months ▪ None developed protein or electrolyte abnormalities ▪ 2 had no complications ▪ 1 had partial loculation ▪ 2 (40%) developed empyema (5 and 15 months after TPC) o One (92 y.o.) died from sepsis Cardiogenic Pleural Effusion

❖ Srour N, Potechin R, Amjadi K. Chest 2013; 1603:1608 ▪ 43 TPCs in 38 patients with CHF ▪ Average age 78.7 years ▪ 2 ipsilateral reinsertion, 3 with contralateral insertion ▪ Catheters remained in place from 5 to 753 days

▪ All had significant dyspnea at baseline (BDI 2.24, 95% CI, 1.53 – 2.94) ▪ Significant improvement in dyspnea was noted (TDI 6.19, 95% CI, 5.56 – 6.82)

▪ None developed empyema ▪ None developed protein or electrolyte abnormalities ▪ ex vacuo developed in 11.6% ▪ None required additional procedures

▪ Successful pleurodesis in 11 patients (29%) ▪ After median of 66 days (interquartile range, 34 – 242 days) ▪ Patients had better performance status (P=0.008) ▪ Patients were less dyspneic (P=0.005) ▪ Patients had longer survival (P=0.0001) Cardiogenic Pleural Effusion: Talc vs. TPC

❖ Freeman et al. Ann Thorac Surg 2014;97:1872 – 1876

▪ Retrospective analysis of 80 patients with class III/IV HF over a 5 year period ▪ 40 patient had TPC vs. 140 had talc (40 / 140 selected) ▪ 2 patient groups formed by propensity matching who had received Thoracoscopic talc vs. TPCs (pre-operative risk factors) o Age, gender, heart failure severity score, Charlson comorbidity score

▪ No significant difference in palliation between groups

▪ TPC group o Shorter stay in hospital (2 vs. 6 days; p < 0.0001) o Lower rate of operative morbidity (2.5% vs. 20%; p=0.03) ▪ (2.5% vs. 12.5%) ▪ PE (0 vs. 2.5%) ▪ A-fib (2.5 vs. 5%) o Operative mortality (0 vs 2 patients) o Lower rate of re-admission (5% vs. 20%; p=0.048) Cardiogenic Pleural Effusion: Talc vs. TPC

❖ Majid A et al. Ann Am Thorac Soc 2016; 13:212-216.

▪ Retrospective review 2005 – 2015 ▪ 2 groups (43 catheters in 36 patients) o Group 1: Thoracoscopy + Talc poudrage + Catheter (N=15) o Group 2: Cather alone (N=28)

▪ Pleurodesis o 80% in Group 1 (median 11.5 Days) o 25% in Group 2 (median 66 Days)

▪ Group 1 was o Younger o Lower NYHA Dyspnea score

▪ Complications similar in both groups o None of the catheters required removal due to adverse event Hepatic Hydrothorax Hepatic Hydrothorax (HH)

❖ Defined as pleural effusion (usually > 500 ml) in patients with ▪ Cirrhosis ▪ Without cardiac, pulmonary or

❖ Transudative pleural effusion

❖ Occurs in 6 – 10% of patients with cirrhosis ❖ One autopsy study of 600 cases, 1% of pleural effusions were attributed to cirrhosis

❖ Vast majority of patients have ascites ▪ However, isolated pleural effusion has been reported (> 30 cases in literature)

1) Xiol X, Guardiola J. Hepatic hydrothorax. Curr Opin Pulm Med 1998; 4:239. Hepatic Hydrothorax (HH)

❖ Pleural effusion is ▪ Generally large, and associated with symptoms ▪ 68% right sided ▪ 16% left sided ▪ 16% bilateral

❖ Diagnosis ▪ Sampling of pleural and ascitic fluid ▪ Intraperitoneal injection of 99mTc sulfur colloid ▪ Introduction of 0.5 – 1L of air into the peritoneal cavity

1) Xiol X, Guardiola J. Hepatic hydrothorax. Curr Opin Pulm Med 1998; 4:239. Hepatic Hydrothorax

❖ Management ▪ Relief of symptoms, bridge to liver transplant o Sodium restricted diet (<88 meq/day) ▪ Only works if 24 hr urinary sodium excretion is more than 78 meq/day o Diuretics ▪ Often Develop diuretic-related complications (refractory hydrothorax) o Therapeutic thoracentesis ▪ Requires frequent procedures ▪ 20% are refractory to medical management

▪ Palliative treatment for those not candidate for transplant

❖ “Chest tubes should not be placed” ▪ Borchardt et al. BMJ 2003:326:751 ▪ Liu et al. Chest 2004: 126:142 Hepatic Hydrothorax (HH) and TIPS

❖ If conservative measures are not effective ▪ Dietary modifications ▪ Diuresis

▪ Transjugular intrahepatic portosystemic shunt (TIPS) o Gordon et al. Hepatology 1997; 25:1366 ▪ 24 patients with refractory hepatic hydrothorax ▪ 21% developed worsening hepatic function and died within 45 days ▪ Not indicated if Child score >10 Hepatic Hydrothorax (HH) and Pleurodesis

❖ Hou F et al Dig Dis Sci 2016; 61:2231 – 3334

▪ Meta-Analysis

▪ 20 case reports with 26 patients o Median age 55 years (7 – 78) o 76% had ascites o 17 (65.4%) had pleurodesis

▪ 13 case series with 180 patients o Mean age 51.5 years o 90% had ascites o 72% successful pleurodesis

▪ Complications were reported in 6 studies (63 patients) o Pooled rate of 82% (95% CI; 66 – 94%) Hepatic Hydrothorax (HH) and Indwelling Catheters

❖ Prospectively maintained data base from 5 UK centres ❖ 57 benign pleural effusion patients (01/2007 – 07/2013) Disease Numbe Mean fluid Spontaneous Median Pleural r (L/week) Pleurodesis days to infection %, (N) Pleurodesis %, (N) Cardiac 9 1.53 44 (4) 38 0 (0) Chylothorax 2 2.4 50 (1) 313 0 (0) Empyema 9 0.42 56 (5) 115 0 (0) Hepatic 19 5.14 11 (2) 222 5.3 (1) HTX Pleuritis 15 2.13 33 (5) 28 6.7 (1) Yellow nail 3 1.15 67 (2) 101 0 (0) syndrome Overall 57 2.8 33 (19) 71 3.5 (2)

Bhatnagar R et al. Thorax 2013; 0:1 – 3 (Epub ahead of print) Hepatic Hydrothorax

❖ Patients “frequently” received albumin infusion ▪ Amount and frequency were not specified

Bhatnagar R et al. Thorax 2013; 0:1 – 3 (Epub ahead of print) Hepatic Hydrothorax (HH) and Tunneled Pleural Catheters

❖ Multicentre, retrospective review of indwelling catheters in HH ❖ 79 patients in 8 US institutions ▪ Catheter placed for palliation in 58 (73%), ▪ Bridge to transplant in 21 (27%)

❖ Median indwell time 156 days (16 – 1978 days) ❖ Spontaneous pleurodesis rate 28% (22 patients) ▪ Median time of 55 days (10 – 370 days)

❖ Renal failure 2 patient, severe electrolyte abnormality 1 patient ❖ Pleural infection 10% (8 patients) ❖ Death from infection 2.5% (2 patients) ❖ No comments regarding albumin infusion

Shojaee A et al. Chest 2019; 155:546 – 553. Hepatic Hydrothorax (HH) and Chest tubes

❖ Retrospective analysis 56 patients CTP class B and C ❖ Chest tube drainage for various indications ▪ Pleural effusion 25 ▪ Pneumothorax 12 ▪ Other 19

❖ Median number of chest drain 5 days (1 – 53 days) ▪ 80% had infection, renal failure, electrolyte imbalance ▪ Pleural infection reported in 48% (27 patients) ▪ 27% died, with infection being the most common cause

Liu LU et al. Chest 2004; 126:142 - 148 Specific issues for Hepatic Hydrothorax

❖ Careful and close monitoring is required

❖ All of our patients are followed up every 2 weeks ▪ Thus, if patient can not follow-up regularly, we do not risk insertion of a catheter o Unless purely palliative

▪ Blood work monitoring liver enzymes, albumin, Bili, renal function, CBC, INR

▪ Transfused 2 – 4 units of 25% albumin per visit ▪ Prophylactic antibiotic if protein <10 g/L

▪ Close collaboration with hepatologists o Monitoring for signs of encephalopathy o Adjustment to their diuretics

❖ Longest running patient with indwelling catheter 620 days ▪ No complications Renal Failure Related Refractory Pleural Effusion Renal Failure related Refractory Pleural Effusion

❖ Isolated renal failure related refractory pleural effusion is rare

❖ Often due to concurrent cardiac or liver failure

❖ Therefore, limited literature on this topic

❖ Potechin R, Amjadi K, Srour N, Indwelling pleural catheters for pleural effusions associated with end-stage renal disease: a case series. Ther Adv Respir Dis 2015;9:22 – 27. Renal Failure related Refractory Pleural Effusion

❖ However, unique cases of pleural effusion can occur secondary to dialysis

▪ 20% of patients on chronic Hemodialysis have a pleural effusion o o Cardiac failure o Parapneumonic process o Uremic pleuritis

▪ 1.6 – 10% of Peritoneal Dialysis patients develop PD-related effusion

Walker et al. Chest 2017; 151:1099 – 1105. Renal Failure related Pleural effusion

❖ 50 year old lady with history of renal failure and on peritoneal dialysis

❖ Presents with increasing SOB and a right sided pleural effusion

❖ Fluid analysis is consistent with patient’s dialysate

❖ Patient preferred to continue with PD and consented to talc pleurodesis

❖ Thoracoscopic talc poudrage was performed successfully ▪ Resumed PD Luks V, Aljohaney A, Amjadi K. Respiration 2013; 67 – 71.

❖ 63 y.o. lady with one month history of progressive dyspnea

❖ Significant past medical history

▪ Ischemic nephropathy, on hemodialysis

▪ Severe PVD (axillo-bifemoral bypass)

▪ MS - L > R pleural and pericardial effusion - No mediastinal LNs or masses

Luks V, Aljohaney A, Amjadi K. Respiration 2013; 67 – 71. Luks V, Aljohaney A, Amjadi K. Respiration 2013; 67 – 71. Luks V, Aljohaney A, Amjadi K. Respiration 2013; 67 – 71.

❖ L pleural fluid analysis : sterile, non-malignant, exudative Chylothorax ▪ LDH = 116 U/L ▪ Protein = 47 g/L ▪ TG = 12.99 mmol/L ▪ Chylomicrons = present

❖ R pleural fluid analysis: sterile, non-malignant, transudative Chylothorax ▪ LDH = 114 (upper limit of normal = 192 U/L, ratio 0.59) ▪ Protein = 29 g/L (serum = 74 g/L) ▪ TG = 2.7 mmol/L

❖ Work-up for lymphoma, malignancy, and TB negative Central venogram showed new onset of SVCO (Hickman)

Luks V, Aljohaney A, Amjadi K. Respiration 2013; 67 – 71. Angioplasty of SVCO Luks V, Aljohaney A, Amjadi K. Respiration 2013; 67 – 71.

❖ Post angioplasty and ultimately stenting of the SVCO ▪ repeat sampling of the pleural effusion revealed transudative process

❖ Rapid decline in fluid re-accumulation resulted in removal of both catheters ▪ L catheter = 151 days ▪ R catheter = 55 days

❖ Complications ▪ Initial drop in lymphocyte count and albumin level, with subsequent rise ▪ Central Line infection ▪ UTI o Had prior history of recurrent UTI and nephrolithiasis Non-malignant Chylothorax Pleurodesis in Benign Chylothorax

❖ Vargas et al. Chest 1994; 106:1771 – 1775 ❖ Gingell JC. Thorax 1965; 261 – 269 ❖ Adler et al. J Thorac Cardiovasc Surg 1978; 76:859 – 864 ❖ Weissberg et al. Ann Thorac Surg 1986; 41:143 – 145 ❖ Fairfax et al. Thorax 1986; 41:880 – 885 ❖ Robinson CLN. Ann Thorac Surg 1985; 39:90 – 95 ❖ Lieberman et al. Cancer 1974; 33:1505 – 1511 ❖ Glazer et al. Chest 2000; 117:1404 – 1409

❖ Pleurodesis in 27 patients with benign chylothoraces (82% success rate) ▪ 20 had talc o Successful pleurodesis in 19/20 ▪ 7 had other agents o Successful pleurodesis in 4/7 Use of Tunneled Pleural Catheters in Chylothorax

❖ DePew et al. Am J Med Sci 2013; 346:349 – 352. ▪ Retrospective analysis of patients persistent benign chylothorax (01/2008 – 03/2012)

▪ 11 patients, 14 hemithoraces had TPCs inserted o 3 post thoracic surgery o 8 non-traumatic ▪ Idiopathic 4 ▪ Yellow nail syndrome 2 ▪ LAM 1 ▪ Chylous ascites 1

▪ Pleurodesis achieved in 9/14 (64%) o Median time 176 days (range 24 – 558 days) Use of Tunneled Pleural Catheters in Chylothorax

❖ DePew et al. Am J Med Sci 2013; 346:349 – 352.

▪ Complications o 1 person had PE “several days” post insertion of catheter (ultimately dies as inpatient)

o 3 patient had occlusion of catheter ▪ 2 successfully treated with intracatheter alteplase ▪ 1 required replacement

o 3 had “clinically insignificant” drop in protein, albumin, and lymphocyte count ▪ No nutritional, hemodynamic, or immunologic adverse outcomes Patil M et al. Chest 2017; 151(3):626 – 635. 13 studies, with 325 patients

Patil M et al. Chest 2017; 151(3):626 – 635. Patil M et al. Chest 2017; 151(3):626 – 635. Patil M et al. Chest 2017; 151(3):626 – 635.

Average pleurodesis rate 51.3% (reported in 9 studies) Patil M et al. Chest 2017; 151(3):626 – 635.

- Estimated overall complication rate 17.2% - Empyema 2.3% Summary

❖ Management of non-malignant pleural effusion can be complex and needs to be tailored for each individual

❖ Chronic indwelling catheters appear to be a safe option in patients with refractory pleural effusions despite maximal medical therapy ▪ Similar complication rates, but lower pleurodesis rates compared to malignant pleural effusion

❖ Patients with hepatic hydrothorax seem to benefit from close monitoring (? albumin infusions)