Controversies in Pleurodesis

By

Gamal Rabie Agmy , MD , FCCP

Professor of Chest Diseases ,Assiut

University

Malignant pleural effusion in general

Median survival following diagnosis ranges from 3 to 12 months and is dependent on the stage and type of the underlying malignancy

The shortest survival time is observed in malignant effusions secondary to lung cancer

Median survival times in effusions due to carcinoma of the breast is up to 15 months

Roberts ME et al. Thorax 2010;65(Suppl 2):32-40

Algorithm for managing MPE

Pleural Diseases, Light RW, 6th ed., 2013

Algorithm for managing MPE

Pleural Diseases, Light RW, 6th ed., 2013

The way to successful pleurodesis

Full lung expansion, no endobronchial obstruction, no trapped lung

Drop in PP of >19 cmH2O after removal of 500 ml of pleural fluid (0/14) Lan RS et al. Ann Intern Med. 1997;126:768-74

Higher possibility for failure but not contraindication:

pH<7.28 (AUC:0.671, 95% CI, 0.624 to 0.715) Heffner JE et al. Chest 2000;117:87-95

Primary tumor: lung cancer (63%) or mesothelioma (61%) vs breast (77%) or other metastatic cancers (74%) as well as the pleural burden

Bielsa S et al. Lung 2011;189:151-5

The way to successful pleurodesis

In case of talc slurry pleurodesis the success rate was higher if:

the time period between radiological diagnosis of

effusion and administration of talc was less than 30

days

spontaneous expansion was attained after chest

tube drainage

daily drainage of less than 200 ml before talc administation

Aydogmus U et al. Ann Surg Oncol. 2009;16:745-50.

Interactive CardioVascular and Thoracic Surgery 12 (2011) 818–823

European Association for Cardio-Thoracic Surgery

What is the best treatment for malignant

pleural effusions? Imran Zahida, Tom Routledgeb, Andrea Bille`b, Marco Scarcib,*

Overall 161 papers concluded that chemical

pleurodesis is superior to chronic catheter drainage

and PPS in terms survival length and mortality rates

but in patients with trapped lung syndrome chronic

intrapleural catheter placement is indicated.

Indwelling Pleural Catheters Reduce

Inpatient Days Over Pleurodesis for

Malignant Pleural Effusion

Conclusions: Patients treated with IPCs required

significantly fewer days in hospital and fewer

additional pleural procedures than those who

received pleurodesis. Safety profiles and

symptom control were comparable

CHEST 2012; 142(2):394–400

Impact of pleural effusion pH on the efficacy of

thoracoscopic mechanical pleurodesis in patients

with breast carcinoma

TMP is a safe palliative

treatment for MPE in breast carcinoma, with a

minimal number of complications and a short

hospital stay; it is more successful than TP in

patients with pH of MPE below 7.3.

European Journal of Cardio-thoracic Surgery 26 (2004)

432–436

Pleural controversy: Pleurodesis versus

indwelling pleural catheters for malignant

effusions Respirology (2011) 16, 747–754

.

Usefulness of pigtail catheter in pleurodesis

of malignant pleural effusion Adel H.A. Ghoneim , Howida A. Elkomy , Ashraf E. Elshora *,

Mohamed Mehrez

Egyptian Journal of Chest Diseases and Tuberculosis (2014)

63, 107–112

Pigtail catheters could be considered a safe, easy,

tolerable and effective alternative method in comparison

to the traditional intercostal tubes in pleurodesis of

malignant pleural effusions.

.

Thoracoscopic

pleurodesis

Indwelling pleural

catheters

More inpatient days Could be placed in an

outpatient basis

The procedure of choice if

there is an undiagnosed

pleural effusion

Many patients prefer to limit

hospital days

More expensive The cost gradually increases

due to vacuum bottles

Higher success rate Home care nursing support

is necessary, the patient

usually dies with the catheter

in place

Mechanism of Pleurodesis

Inflammatory injury to the pleura

Light RW et al. Am J Respir Crit Care Med 2000;162:98–104

Small particle-size talc is associated with increased inflammation

Arellano-Orden E et al. Respiration 2013;86:201-9

Corticosteroids and pleurodesis

Pleurodesis with talc can be blocked with systemic administration of corticosteroids

Xie C et al. Am J Crit Care Med 1998; 157: 1441–4

The pleurodesis following intrapleural TGF-β is not

inhibited by corticosteroids Lee YCG et al. Thorax 2001;56:643

Coagulation Cascade - Fibrinolytic Activity - Proliferation of fibroblasts

Decrease in D-dimers 24h after talc poudrage is

associated with successful pleurodesis Psathakis K et al. Eur Respir J 2006; 27: 817-21.

Patients with successful pleurodesis after talc insufflation

have significantly higher levels of bFGF in their pleural

fluid and there is a significant negative correlation

between bFGF levels and tumor size. Antony VB et al. Chest 2004;126:1522-8

Pleural adhesions are reduced after tetracycline if either

heparine or urokinase are given intrapleurally Strange C et al. Am J Respir Crit Care Med 1995;151:508-15

VEGF – angiogenesis and pleurodesis

Intrapleural administration of TGF-β

and anti-VEGF IV

r =0.84, p<0.01

Guo YB et al. Chest 2005; 128:1790-7

Sclerosing agents – The

procedure of pleurodesis

Lee YCG et al. Chest 2003; 124:2229-38

Agent Comments

Talc (4 gr) Inexpensive, widely available, high success

rate, much more studies, graded type (French

talc), ―gold‖ standard

Tetracycline (1.5 gr)

doxycycline (500 mgr)

minocycline (400 mgr)

The second most usually used, complete

success rate: 60-65%, severe chest pain

(lorazepam, midazolam)

Bleomycin (0.75 mgr/kg) Success rate: 50-54%, expensive

Mitoxantrone (40 mgr) A few studies, cardiotoxicity, very expensive

Silver nitrate (20 ml, 0.5%) The first agent that was used, a few clinical

studies with small number of patients

Iodopovidone (100 ml, 2%) Promising agent with high success rate (>80%),

inexpensive, widely available, a few clinical

studies

Other agents

Corynebacterium parvum Walker-Renard PB et al. Ann Intern Med

1994;120:56-64

Nitrogen mustard Kinsey DL et al. Arch Surg 1964;89:389-91

OK-432 Kishi K et al. Eur Respir J 2004;24:263-6

Quinacrine Ukale V et al. Lung Cancer 2004;43:323-8

Talc is the most effective sclerosant available for pleurodesis. (A)

Graded talc should always be used in preference to

ungraded talc as it reduces the risk of arterial hypoxaemia complicating talc pleurodesis. (B)

Talc pleurodesis is equally effective when

administered as a slurry or by insufflation. (B)

Roberts ME et al. Thorax 2010;65(Suppl 2):32-40

Talc Pleurodesis for the Management of Malignant Pleural

Effusions in Japan

Intern Med 52: 1173-1176, 2013

Talc pleurodesis is an effective and safe treatment for the

management of malignant pleural effusion

in Japanese patients.

TP was significantly more effective than TS;

both methods were safe but TS had a higher

incidence of thoracic pain during the procedure

Talc poudrage versus talc slurry in the treatment of

malignant pleural effusion.

A prospective comparative study

Alessandro Stefani, Pamela Natali, Christian Casali,

Uliano Morandi

European Journal of Cardio-thoracic Surgery 30 (2006)

827—832

•18 RCTs and

2 non-RCTs

• 1,525 patients

with MPE who

underwent

pleurodesis

Xia H et al. PLoS ONE 2014;9(1):e87060.

Efficacy and Safety of Talc Pleurodesis for

Malignant Pleural Effusion: A Meta-Analysis

PLoS ONE 9(1):January 27, 2014

The success rate of talc pleurodesis was significantly

higher than that of control therapies (relative risk,

1.21; 95% confidence interval, 1.01–1.45;p = 0.035)

with similar adverse events. In addition,

thoracoscopic talc poudrage was more effective than

bedside talc slurry (relative risk, 1.12; 95%

confidence interval, 1.01–1.23; p = 0.026).

Both methods of talc delivery are similar in efficacy; TTI may be better for

patients with either a lung or breast primary

Dresler CM et al. Chest 2005; 127:909-15.

Side Effects TALC POUDRAGE

(N = 26)

TALC SLURRY

(N = 29)

ACUTE PAIN 0 7 (24%)

FEVER 6 (23%) 10 (34%)

DYSPNEA

0 1 (3%)

RECURRENCES 1 (4%) 8 (27%)

Mañes et al, RANDOMIZED STUDY (CHEST 2000; 118,4 Suppl:131s)

TALC POUDRAGE vs TALC SLURRY?

3 hrs. Post-”poudrage” 3 hrs. Post-”slurry”

TALC “SLURRY”: Is the patient receiving the RIGHT DOSE OF TALC?

(Adapted from Rodriguez-Panadero et al, Eur Respir J 2006;28:200-218)

Thoracoscopic talc poudrage: observational studies

Viallat JR et al. Chest 1996;110:1387-93

360 patients with MPE, 90.2% success rate at 1 month and 82.1% life-long pleural symphysis

Ribas Milanez de Campos et al. Chest 2001;119:801-6

393 patients with MPE, success rate: 96.4% for breast cancer and 93.4% for other malignancies

Kolschmann S et al. Chest 2005; 128:1431–5

102 consecutive patients with MPE, success rate was 89.4% at 1 month and 82.6% at 6 months

Rodriguez-Panadero F et al. Respiration 2012;83:91-8

460 patients with MPE, success rate: 87.4%

TTI (=“Talc poudrage” was performed in general anesthesia and double-lumen tracheal intubation!!

TYPE OF TALC NO SPECIFIED,

NOR SIZE OF PARTICLES!!

TALC + DOLOMITE TALC

TALC + CALCITE

FRANCE

VERMONT, USA

YELLOWSTONE, MONTANA, USA

Multicentre (13 European

hospitals, and one in South

Africa), open-label, prospective

cohort study of 558 patients with

malignant pleural effusion who

underwent thoracoscopy and talc

poudrage with 4 g of calibrated

French large-particle talc

Janssen JP et al. Lancet 2007; 369: 1535-9

Betadine for pleurodesis

Study

Comments

Olivares-Torres CA et al.

Chest 2002;122:581-3 Prospective study, CRR: 50/52

(96.1%), mean follow-up: 13±1.46

months, 3 patients intense pleuritic

pain

Agarwal R et al.

Respirology 2006;11:105-8 Prospective study, CRR: 32/37

(86.5%), mean follow-up: 5 months

Neto JD et al.

Respirology 2010;15:115-8 Retrospective study, 61 procedures

in 54 patients, success rate: 98.4%,

mean follow-up: 5.6 months

Mohsen TA et al.

Eur J Cardiothorac Surg 2011;40:282-6 RCT, MPE due to breast cancer,

success rate: 20/22 (91%) with talc

poudrage and 17/20 (85%) with

betadine

IN SUMMARY: (Up to date) talc is the sclerosant of choice for control of malignant pleural effusions

• Achieves control of effusions in about 90% of the cases

• It can be used as poudrage (preferred) or slurry.

• Low cost

• Low rate of complications in large series

• BE CAREFUL ABOUT:

• - USING TRUE TALC

• - SIZE OF TALC PARTICLE

• - AVOID USE OF PRESSURIZED SPRAYS (can be very cold and with additives as propellents)

• - GIVE PROPHYLACTIC HEPARIN

Careful selection of patient and the appropriate procedure is the first step to successful management

Graded talc is the sclerosing agent of first choice

As medical thoracoscopy is the gold standard for every undiagnosed pleural effusion, in case of MPE talc poudrage at the same time is absolutely indicated

The opportunity of TPCs should always be discussed with the patient

Pleurodesis: practical issues (1)

Small-bore chest tubes are equally effective with large-bore

Negative pressure should be applied after 24 hours if there is

no full lung expansion

Corticosteroids and NSAIDs reduce the success rate

Do not administer sclerosing agent in case of trapped lung

It is not necessary to wait for fluid production <150 ml/24h if

there is full lung reexpansion

Caglayan B et al. Ann Surg Oncol 2008;15:2594-9, Teixeira LR et al. Chest 2002;121:216-9, Lardinois D et al.

Eur J Cardiothorac Surg 2004;25:865-71, Villanueva AG et al. Thorax 1994;49:23-5

Pleurodesis: practical issues (2) In case of loculated MPE, administration of fiblinolytics

intrapleurally have been used before pleurodesis

Even though it is a common practice, there are no RCTs that evaluated the efficacy of intrapleural lidocaine

Rotation of the patient after administration of the agent does not increase success rate but may reduce pain

There are no RCTs about how many days the chest tube should remain after the administration of talc (fluid production <150 ml/24h)

Hsu LH et al. J Thorac Oncol 2006;1:460-7, Lorch DG et al. Chest 1988;93:527-9, Dryser SR et al. Chest

1993;104:1763-6,