Review Article

PULMON
Pulmon 2007; 9 : 2 : 51 - 56

Medical Pleurodesis

Venugopal P
Assistant Professor
Dept. of Respiratory Medicine
Alappuzha Medical College

aircrew, divers, patients living in remote areas,

Key words patients having a single lung.
Pleurodesis, Sclerotherapy
q First pneumothorax life threatening

q Bullous disease
Definition:
q Catamenial pneumothorax
Pleurodesis (Sclerotherapy) is defined as a procedure
aimed at making adhesions between the visceral and q When surgical pleurodesis is contraindicated
parietal pleura, obliterating the potential pleural space.
Recurrent pleural effusion
Pleurodesis was done first by Spengler in early 19th
century1. Pleurodesis can be Chemical (Medical) or q Malignant pleural effusion – primary lung,
Surgical - Surgical Pleurodesis includes pleural abrasion, secondary, mesothelioma
pleurectomy and Video Assisted Thoracoscopic q Benign recurrent pleural effusion – chylothorax,
procedures. Chemical pleurodesis is an accepted palliative pleural effusion associated with connective tissue
therapy for patients with recurrent, symptomatic malignant diseases, nephrotic syndrome, cardiac failure,
pleural effusions. Various chemicals have been used in an cirrhosis, etc
attempt to produce pleurodesis.
q Pleuroperitoneal communication during long-term
Indications 2
peritoneal dialysis
Pneumothorax
Contraindications
q Recurrent pneumothorax - primary spontaneous
q If the patient is a candidate for lung transplantation
q Ipsilateral recurrence, contralateral occurrence e.g. Cystic Fibrosis, Lymphangioleiomyomatosis,
etc, due to fear of difficulty in separating adhesions
q Bilateral simultaneous pneumothorax
and chances of severe bleeding, pleurodesis is better
q First pneumothorax in special risk groups e.g. avoided. Although pleurodesis increases the risk for

Dr.P.Venugopal 51
Assistant Professor
Dept. of Respiratory Medicine
Alappuzha Medical College
 postoperative hemorrhage in patients who ultimately
require lung transplantation, this complication is
usually manageable and prior pleurodesis does not
usually affect candidacy for transplantation. Given
the morbidity of multiple pneumothoraces, many
recommend pleural fusion on the first event.
q Known hypersensitivity to the sclerosing agent
q Trapped lung (prevention of lung reexpansion by
narrowing of the lobar bronchus due to an extrinsic
or intrinsic tumor, or by the encapsulated visceral
pleura)
Mechanisms of Pleurodesis
When the sclerosing agent has contacted the
metabolically active mesothelial cell, an interleukin 8 (IL-
8)-mediated neutrophil influx into the pleural space occurs
and is subsequently followed by macrophage accumulation.
The stimulated macrophages also release IL-8, in addition
to macrophage chemo attractant protein 1 (MCP-1), and
in the presence of adhesion molecule expression on the
mesothelial cell may amplify the inflammatory response.
In successful pleurodesis, pleural fibrinolytic activity
declines, suggesting an important role of the coagulation
cascade. Finally, there is a rapid and marked rise in basic
fibroblast growth factor (bFGF) in pleural fluid that is
derived from mesothelial cells3. When there is extensive
tumor covering the mesothelium, pleurodesis is less
effective, further supporting the key role of the mesothelial
cell in pleural fibrosis.
Prerequisites for Pleurodesis 4
q Patients selected for pleurodesis should have
significant symptoms that are relieved when pleural
fluid is evacuated.
q There should be evidence of complete re-expansion
of the lung without evidence of bronchial obstruc-
tion or fibrotic-trapped lung.
q Daily tube drainage is less than 100 mL
q Pleurodesis should be reserved for those cases
where there is no other therapeutic alternative, or
when this has already failed.
q If the patient undergoing pleurodesis is receiving
52 Pulmon 2007; 9 : 2 : 51 - 56
corticosteroid therapy, the drug should be stopped
or the dose reduced if possible because of concerns
of decreased efficacy of pleurodesis
Sclerosing agents
· Conventional agents
· Agents used in the past
· Newer agents
Conventional agents
· Talc
· Tetracycline derivatives
· Corynebocterium parvum
· Bleomycin
Agents used in the past
· Nitrogen mustard- induces pleurodesis,
but causes important side effects5.
· Kaolin
· Radioactive colloidal gold
· Quinacrine
· 50% glucose solution
· Autologous blood
· Iodised oil
Procedure of pleurodesis:
Most commonly, pleurodesis is performed via a
standard tube thoracostomy. Radiographical confirmation
is then obtained to demonstrate complete re-expansion of
the lung in evacuation of the fluid. Narcotic analgesics
and/or sedation are often recommended because of the
pain associated with many sclerosing agents. The
sclerosing agent of choice is then added to the chest tube,
typically in a solution of 50–100 ml of sterile saline. The
chest tube is then clamped for 1 h, without rotation of the
patient being required. The chest tube is then subsequently
reconnected to 20-cmH2O suction. It is then recommended
that suction be applied to the chest tube until the 24-h output
from the chest tube is <150 ml.
Prior studies of pleural sclerosing solutions have
proven that patient rotation is unnecessary, as the solution
likely spreads by capillary action6. However,
rotation is advised if even a minimal of air is present,
or when there are loculations.
Medical Pleurodesis
Tetracycline derivatives7:
For many years, tetracycline was the sclerosing agent
of choice. However, when it became commercially
unavailable, alternative agents were investigated.
Doxycycline, a tetracycline analogue, has been
recommended as a replacement for tetracycline. Although
there are no direct studies comparing doxycycline with
tetracycline, pleurodesis studies have demonstrated clinical
success rates with doxycycline that are similar to those
with tetracycline, with a success rate of up to 80–85% in
carefully selected patients. Most studies have
recommended the utilization of 500 mg of doxycycline
mixed with 50–100 cm3 of sterile saline (or mg/kg body
wt of tetracycline). As pain is the most common
complication associated with doxycycline pleurodesis,
narcotic analgesic and/or conscious sedation is often
recommended or the solution may be mixed with 10 ml of
15 lignocaine to reduce pain.
Bleomycin8
Another agent frequently recommended for
pleurodesis is bleomycin. Most studies have used a dose
of 60 IU of bleomycin mixed with 50–100 ml of sterile
saline. Most studies demonstrated similar or higher success
rates when utilizing bleomycin as a sclerosing agent,
compared with tetracycline. A direct study comparing
doxycycline with bleomycin pleurodesis utilizing a small-
bore catheter, demonstrated similar success rates (72%
with bleomycin, 79% with doxycycline) 9. As stated
previously, direct studies comparing talc and bleomycin have
demonstrated a superior pleurodesis success rate with talc.
An important criticism of bleomycin as a sclerosing agent
involves its relative expense as compared with other
sclerosing agents such as talc or doxycycline.
Talc pleurodesis
Talc is a pulverized, natural, foliated, hydrated
magnesium silicate with the approximate chemical for-
mula Mg3(Si2O5)2(OH)2. A review of published series found
a 93% success rate (153 of 165 patients) for talc pleurodesis
in the treatment of malignant pleural effusion10.
Talc pleurodesis may be done by two methods:
Talc poudrage
The most widely reported method of talc instillation
into the pleural space for malignant effusion is talc
Pulmon 2007; 9 : 2 : 51 - 56
poudrage, which is usually performed under thoracoscopic
guidance. Talc poudrage can be performed by medical
thoracoscopy under local anesthesia with conscious
sedation or by VATS. Although an optimal dose of talc for
poudrage has not been established, 5 g is usually
recommended for malignant effusions11.
Talc slurry
Mixing talc with normal saline and gently agitating
makes the slurry. Potential disadvantages of slurry include
lack of uniform distribution, accumulation in dependent
areas of the pleural space possibly leading to incomplete
pleurodesis and loculations, and decreased direct contact
time with the pleural surface due to the liquid suspension
with subsequent decrease in effectiveness. Patient rotation
is recommended in talc slurry.
Fever up to 102.4° F after talc pleurodesis has been
reported to occur in 16–69% of patients. Empyema has
been reported with talc slurry in upto 11% of procedures,
whereas talc poudrage is associated with an incidence rate
of only 0–3% of patients. Local site infection is uncommon,
and the degree of pain associated with talc has reportedly
ranged from nonexistent to severe. Cardiovascular
complications such as arrhythmias, cardiac arrest, chest
pain, myocardial infarction, or hypotension have been noted;
whether these complications result from the procedures
or are related to talc per se has not been determined. Acute
respiratory distress syndrome (ARDS), acute pneumonitis,
and respiratory failure have also been reported to occur
after both talc poudrage and slurry12. In an experimental
study using talc slurry, Kennedy et al. found prominent
perivascular infiltrates with mononuclear inflammation in
the underlying lung, and it was speculated that mediators
might spread through the pulmonary circulation after
application of the sclerosing agent13. Other possible causes
of acute respiratory failure with talc pleurodesis include
sepsis due to nonsterile or endotoxin-containing talc,
excessive talc dosing, active air leak, excessive
periprocedure medications, severe underlying lung disease,
and re-expansion pulmonary edema.
Long-term effects of Talc:
Twenty-two to 35 yrs after talc poudrage of
pneumothorax, total lung capacity averaged 89% of
predicted in 46 patients, whereas total lung capacity was
Medical Pleurodesis 53
97% of predicted in 29 patients treated with tube
thoracostomy alone 14 . None of the poudrage group
developed mesothelioma over the 22- to 35-yr follow-up.
Although talc poudrage may result in minimally reduced
total capacity, as well as pleural thickening on chest
radiography, these changes appear to be clinically
unimportant. A link between talc and cancer has been
reported in those who mine and process talc but this
association is attributed to asbestos, which is commonly
found with talc, rather than to talc itself. No increase in
lung cancers was found in a group of patients who had
talc pleurodesis for pneumothorax and had long-term
follow-up.
The following precautions are recommended to
minimize complications during talc pleurodesis15:
q No more than 5 g of talc should be used. Two grams
of talc is used, in contrast with the 5 g recommended
for pleurodesis of malignant pleural effusions
q Bilateral simultaneous pleurodesis not to be
attempted
q Talc from which most particles of less than 15 µm
have been removed is probably a safer agent for
pleurodesis than standard mixed talc
q Concomitant pulmonary biopsy should be avoided.
Light’s recommendation16- if the patient is diagnosed
malignant pleural effusion during thoracoscopy or
thoracotomy, talc insufflation should be done, if the
diagnosis is by less invasive methods, talc slurry or other
agents are preferred.
Combined use of various drugs.
It has been suggested that talc and doxycycline might
be acting through different pathways in creating
pleurodesis. Hence combinations of various agents in
lesser doses would be synergistic in inducing pleurodesis.
Oner Dikensoy and team has used doxycycline and talc in
half the usual doses and found success in rabbits17.
Success or failure of pleurodesis
Since low pleural fluid pH (values at or below pH
7.28) is a marker of increased metabolic activity of intra-
pleural tumor collections, which corresponds to increased
54 Pulmon 2007; 9 : 2 : 51 - 56
tumor bulk, low pleural fluid pH has been suggested to
predict failure of pleurodesis in malignant pleural effusion18.
Definitions of success or failure of pleurodesis
Uniform criteria for evaluating the results of pleurodesis
in future studies are badly needed. The following
definitions are proposed by V.B. Antony et al 19:
Completely successful pleurodesis - absence of fluid
reaccumulation on chest radiographs until death.
Partially successful pleurodesis - Diminution of
dyspnea related to the effusion, with only partial
reaccumulation of fluid (<50% of the initial radiographic
evidence of fluid), with no further therapeutic thoracentesis
required for the remainder of the patient’s life.
Failed pleurodesis: Lack of success
Treatment of pleurodesis failure
Causes of failure being sub optimal techniques or
inappropriate patient selection (e.g. a patient with a trapped
lung or main stem bronchial occlusion).
Several alternatives:
o Repeat pleurodesis with another sclerosant
o Repeat thoracentesis
o Pleuroperitoneal shunting or pleuroectomy
o Chronic thoracostomy drainage catheter and bag
Which agent is preferred?
Recently a survey was conducted among
Pulmonologists about Pleurodesis Practice for
Malignant Pleural Effusions, published in Chest, 2003.20
According to this study, most effective agent is talc
(90%) followed by Corynebacterium parvum 76%,
doxycycline 72% and tetracycline 67%. Reported
success rate averaged only 66% and most thought that
the agents currently available are suboptimal. Complete
success rates of commonly used pleurodesis agents
were as follows: Talc 93%, Corynebgcterium parvum
76%, Doxycycline 72%, Tetracycline 67%, Bleomycin
54%). Adverse effects of commonly used pleurodesis
agents as per this study were Chest pain ( Talc 7%,
Doxycyline 40 %, Bleomycin14%) and fever (Talc
16%, Tetracycline 31%, Bleomycin 24%).
Flurodeoxyglucose PET (FDG- PET) Scan should be
interpreted with caution in patients who have
Medical Pleurodesis
 undergone talc pleurodesis, since this will lead to
increased uptake of FGD in areas where high density
plaques have developed21.
Search for an ideal Pleurodesis Agent -The
ideal chemical for pleurodesis should be highly
effective, easy to administer, inexpensive, virtually free
of adverse effects, and not associated with serious
adverse events. Such an agent is yet to be discovered.
Sclerosing agents under evaluation:
Ø Mitoxantrone
Ø Iodopovidone
Ø Transforming growth factor beta2
Ø Silver nitrate
Ø Sodium hydroxide
Ø Oral forms of tetracycline: Oral tetracycline or
doxycycline is as effective and safe as parenteral
doxycycline in producing pleurodesis in rabbits; thus,
they may also be used in humans22.
Ø Facial talc
Ø Iodopovidone
• Iodopovidone
Iodopovidone is a promising, readily available, cheap,
safe and effective sclerosing agent and has antiseptic
effect. In a study in Mexico, Iodopovidone pleurodesis in
52 patients proved to be successful in 5023. Only side
effects noted were mild pain and transient hypotension.
20 mL 10% Iodopovidone and 80 mL normal saline solution
was used. Contraindicated in iodine allergy, thyrotoxicosis,
patients being prepared for radioactive iodine uptake scans.
A recent report of five cases of Potassium iodate induced
toxic retinopathy following pleurodesis is of concern24.
However, povidone–iodine pleurodesis with the use of 20
ml of 10% povidone–iodine is thought to be safe.
Transforming growth factor beta2
Another promising agent, found to be successful in
Pulmon 2007; 9 : 2 : 51 - 56
rabbits, but expensive.
TGF ß 2 is a fibrogenic cytokine with immunomodulatory
functions, could induce effective pleurodesis without
generating significant pleural inflammation and therefore
remain effective despite co-administration of
corticosteroids25. It is capable of inducing pleurodesis
significantly faster than talc.
Silver nitrate 0.5% produces higher adhesions than talc,
mild and reversible alveolar collapse and an eosinophilic
response. Silver nitrate produces a better pleurodesis than
does the intrapleural injection of 400 mg/kg of talc slurry
in rabbits26.
Laser pleurodesis:
Nd-YAG laser via thoracoscopy has been
successfully used as a viable therapeutic option in patients
with spontaneous pneumothorax27. Using an Nd-YAG
laser beam via thoracoscopy, the parietal pleura is abraded.
Ambulatory Sclerotherapy:
The traditional method of treatment—tube
thoracostomy with large-bore chest tubes connected to
continuous wall suction— requires hospitalization, is
expensive, limits patient mobility, and can cause significant
patient discomfort. More recent trials have explored new
techniques, including thoracoscopic insufflation of talc and
small-bore catheters. Most of these studies have been
performed on inpatients, although a recent multi-institu-
tional trial was initiated to evaluate the feasibility and
efficacy of ambulatory (outpatient) pleural drainage and
sclerotherapy using small-bore catheters. A small-bore
catheter placed in the pleural space that is then connected
to a closed gravity drainage bag system. When daily tube
drainage was <100 mL, sclerotherapy is performed. The
preliminary results suggest ambulatory sclerotherapy is a
safe, viable alternative to conventional inpatient treatment
of malignant pleural effusions in a select group of
patients28.
Medical Pleurodesis 55
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Medical Pleurodesis