Original Thoracic

Early Autologous Blood-Patch Pleurodesis

versus Conservative Management for Treatment
of Secondary Spontaneous Pneumothorax
Islam M. Ibrahim1 Montaser Elsawy Abd Elaziz1 Mohammed Ahmed El-Hag-Aly1

1 Department of Cardiothoracic Surgery, Faculty of Medicine, Address for correspondence Mohammed Ahmed El-Hag-Aly, MD,
Menoufia University, Menoufia, Egypt Department of Cardiothoracic Surgery, Faculty of Medicine, Menoufia
University, Shebeen El-Kom, Menoufia 23511, Egypt
Thorac Cardiovasc Surg (e-mail: elhagalycts@gmail.com).

Abstract Background Autologous blood-patch pleurodesis has been effectively utilized as a

treatment option for the condition of secondary spontaneous pneumothorax (SSP).
Moreover, it can be used with persistent air leak, with or without residual air space.
However, there have been no robust reports for the optimal timing for autologous
blood-patch pleurodesis. The aim of this study is to compare early autologous blood-

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patch pleurodesis with conservative management of SSP.
Methods We conducted a randomized controlled study at the Menoufia University
Hospital. A total of 47 patients with SSP were randomly allocated into two groups:
group A (23 patients) received intrapleural instillation of 50 mL autologous blood
3 days after insertion of chest drain and group B (24 patients) managed conservatively.
The duration required for air leak to seal, chest drainage duration, length of hospital
stay, and the incidence of complications were compared and statistically analyzed.
Results The duration of air leak, duration to drain removal, and length of hospital stay
Keywords were all significantly shorter in group A than in group B.
► pleura Conclusion Early intrapleural instillation of autologous blood is successful in sealing
► air leak air leak in patients with SSP with persistent air leak, who are not fit or not willing to
► effusion undergo surgery. It is superior to conservative treatment or late instillation of
► pneumothorax autologous blood, even if their lungs are not fully expanded.

Introduction persistent air leak.3 Subsequently, SSP can be hazardous

Spontaneous pneumothorax secondary to chronic obstruc-
tive pulmonary disease (COPD) and other interstitial lung
diseases carries a higher risk of complications and mortality
than primary spontaneous pneumothorax (without under-
lying pulmonary disease).1 The mechanism of secondary
spontaneous pneumothorax (SSP) is usually a consequence
of ruptured acquired subpleural cystic air spaces (bleb or
bulla) related to the underlying lung pathology.2 Re-expan-
sion of the lung can be inhibited by the rigidity of lung
parenchyma associated with the underlying pathology. In
addition, those patients are usually on corticosteroids, which
inhibit the healing process of the injured lung causing
and frequently exhibited as a difficult-to-treat illness.
Insertion of intercostal chest tube drain is usually the
initial prompt treatment for patients with SSP. If air leak
persists for a period of more than 48 hours, further treat-
ment should be considered.4 The latest British Thoracic
Society guidelines recommend surgical intervention as a
treatment option in those patients.4 Such patients are
usually considered as being not good candidates for surgical
intervention due to the severity of their underlying lung
disease. Chemical pleurodesis using talc, antibiotics, or
antineoplastics has been reported and accepted as a treat-
ment option.5–7 Chemical pleurodesis, however, is ineffec-
tive when the lung is not fully inflated.

received © Georg Thieme Verlag KG DOI https://doi.org/

February 2, 2018 Stuttgart · New York 10.1055/s-0038-1642028.
accepted after revision ISSN 0171-6425.
February 22, 2018
Blood-Patch Pleurodesis for Pneumothorax Ibrahim et al.
SSP can be effectively controlled and treated by the utiliza-
tion of autologous blood-patch pleurodesis technique.8–13 The
instillation of autologous blood into the pleural space is a safe,
simple, painless, and inexpensive procedure for treating SSP.
Moreover, it can be used with persistent air leak, with or without
fully inflated lung.9 However, there have been no reports, for the
best timing for autologous blood-patch pleurodesis.
The aim of this study was to compare between early
autologous blood-patch pleurodesis and conservative man-
agement for treatment of SSP.
Materials and Methods
This randomized controlled study was performed between
November 2012 and November 2015 at the Menoufia Univer-
sity Hospital in Egypt. The sample size was determined by public
health department, based on the previous related published
studies, and sample size between 40 and 50 was found to be
Fig. 1 Flow diagram of patients allocated in the study.
Thoracic and Cardiovascular Surgeon
statistically appropriate (18–20–21–22). Forty-seven patients
having SSP (39 men and 8 women) were enrolled in the study
(►Fig. 1). Their age ranged from 36 to 76 years. Our entire
patient cohort was unfit or unwilling to have surgery. Informed
consent was obtained from all patients and ethical approval for
the study was obtained from the local ethics committee.
As soon as a confirmed pneumothorax diagnosis was
ascertained by chest X-ray, prompt initial treatment was
achieved for all patients by insertion of a chest tube drain
(size 24F–28F) in the fifth intercostal space anterior axillary
to mid-axillary lines. The chest drains were apically directed.
All patients had persistent air leak for at least 3 days after
chest drain insertion.
The 47 patients included in the study were randomly
allocated in two groups sequentially, group A (23 patients)
and group B (24 patients). Our patient cohort represented a
homogenous sample; the two groups were evenly matched for
age, sex, severity of lung disease, and size of air leak (►Table 1).
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 Blood-Patch Pleurodesis for Pneumothorax Ibrahim et al.

Table 1 Patients baseline characteristics gentle respiration), and size 3 (large continuous air leak on
gentle respiration).14
Variable Group A Group B p-Value The primary end points of the study were time to seal off
Male sex a
19 (82.6%) 20 (83.3%) 0.947 the air leak, time to drain removal, and time to hospital
Age (y)b 57.6 ! 10.2 61.6 ! 10.0 0.176
discharge (all expressed as days with respect to the day of
chest drain insertion). The success of the treatment was
Smoking
defined as air leak sealed within 7 days from chest drain
Current smokera 16 (69.6%) 16 (66.7%) 0.733 insertion, without recurrence of pneumothorax within
Ex-smokera 3 (13.0%) 5 (20.8%) 7 days of chest drain removal. Complications such as fever,
Nonsmokera 4 (17.4%) 3 (12.5%) pain, pleural effusion, and infection were also evaluated.

Size of air leak (day 3)

Statistical Analysis
Size 1a 4 (17.4%) 4 (16.7%) 0.896 Statistical analysis was performed using RStudio Version
Size 2a 10 (43.5%) 12 (50.0%) 0.99.489 2009–2015 RStudio, Inc. The durations of air leak
Size 3a 9 (39.1%) 8 (33.3%) seal, chest drainage, and hospital stay were expressed as
mean ! standard deviation (SD). The size of air leak, number
Lung fully inflated 7 (30.4%) 8 (33.3%) 0.831
(at first pleurodesis)a of pleurodesis, and incidence of complications were expressed
as percentage. Differences between the groups were explored
a
Number (%). using Student’s t-test for continuous variables and a chi-square
b
Mean ! standard deviation.
(χ2) test for categorical variables. Differences were considered
significant if the p-value was less than 0.05.

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Patients of group A received intrapleural instillation of 50 mL
autologous blood 3 days after insertion of chest drain, while
patients in group B were managed conservatively by observa-
tion, bronchodilators, and physiotherapy. Patients in group B
who continue to have air leak for 10 days received intrapleural
instillation of 50 mL autologous blood 10 days after insertion
of chest drain (if air leak persist). All other treatment strategies
for these patients were standardized.
The procedure was performed on the cardiothoracic
surgical ward at Menoufia University Hospital at the
patient’s bedside under aseptic conditions (mask, surgical
scrub, and sterile gloves). No sedation or special analgesia
was used in any patient. Venous blood was withdrawn from
the patient’s forearm using a 50-mL syringe. Anticoagulant
agents such as heparin were not added. Immediate instilla-
tion of autologous blood into the pleural cavity was achieved,
after a brief period of chest tube clamping, through the
connector between the chest tube and underwater drainage.
The tube was kept at around 60 cm over the patient’s chest
for 2 hours to keep reverse of blood from the cavity. All
patients remained in bed for 2 hours after instillation and
were encouraged to turn from side to side in the bed every
15 minutes to promote homogeneous distribution of blood
within the pleural cavity. No suction was administered to the
underwater seal system after blood instillation. The proce-
dure was repeated 2 and 4 days after the first procedure if the
air leak was still present (on days 5 and 7 post-chest drain
insertion for patients in group A, and on days 12 and 14
postchest drain insertion for patients in group B).
The presence and size of air leak were observed and
recorded daily for every patient. The chest drains were
removed 2 days after the disappearance of the air leak. All
of our patients were closely observed for a period of at least
1 week after thoracostomy tube removal. The size of air leaks
were classified as: size 0 (no air leak), size 1 (air leak on
vigorous coughing only), size 2 (small continuous air leak on
Results
Forty-seven patients with SSP were included in our study and
randomized into two groups. Group A included 23 patients
(19 males and 4 females) who had early autologous blood-
patch pleurodesis at day 3 after insertion of chest drain and
group B included 24 patients (20 males and 4 females) who
were managed conservatively. The age of the patients ranged
from 36 to 76 years with a mean age ! SD of 57.6 ! 10.2 years
for group A and 61.6 ! 10.0 years for group B (►Table 1). Of
each group, 16 patients (69.6% of group A and 66.7% of group B)
were current smokers. Three patients (13.0%) of group A and
five patients (20.8%) of group B were ex-smokers, while four
patients (17.4%) of group A and three patients (12.5%) of group
B were nonsmokers (►Table 1). There was no statistically
significant difference between both groups regarding sex
(p ¼ 0.947), age (p ¼ 0.176), or smoking history (p ¼ 0.733)
(►Table 1).
On day 3 after chest drain insertion, the size of air leak in
group A patients were size 1 in 4 patients, size 2 in 10 patients,
and size 3 in 9 patients. The size of air leak in group B patients
on day 3 were size 1 in 4 patients, size 2 in 12 patients, and size
3 in 8 patients. The lung was fully inflated in seven patients
(30.4%) of group A and eight patients (33.3%) of group B. There
was no statistically significant difference between both groups
regarding the size of air leak on day 3 (p ¼ 0.896) or the
number of patients with lungs fully inflated (p ¼ 0.831) at
day 3 after chest drain insertion (►Table 1).
All patients in group A had autologous blood-patch pleur-
odesis at least once (one pleurodesis in 6 patients, two
pleurodesis in 12 patients, and three pleurodesis in 5 patients),
while in group B, 16 out of the 24 patients still had an air leak by
the 10th day after chest drain insertion so they had pleurodesis
(one pleurodesis in six patients, two pleurodesis in nine
patients, and three pleurodesis in one patient). The mean
duration of air leak ! SD was 5.43 ! 1.27 days in group A

Thoracic and Cardiovascular Surgeon

Blood-Patch Pleurodesis for Pneumothorax Ibrahim et al.

Table 2 Procedure data COPD is the commonest incriminated lesion for SSP. The
initial treatment for SSP is tube thoracostomy, which unfor-
Variable Group A Group B p-Value tunately can be associated with persistent air leak or col-
Number of pleurodesis lapsed lung for more than 7 days in approximately 20% of
Nonea 0 8 (33.3%) 0.011 patients.15 These patients are usually treated surgically with
a
thoracotomy or thoracoscopy under general anesthesia.4
One 6 (26.1%) 6 (25.0%)
Some patients, however, are not fit for surgery or general
a
Two 12 (52.2%) 9 (37.5%) anesthesia, due to old age, underlying lung pathology, or
Threea 5 (21.7%) 1 (4.2%) compromised pulmonary function, and an alternative treat-
Days to air 5.43 ! 1.27 10.54 ! 3.09 < 0.001 ment would be required.
leak sealb Robinson10 first reported the technique of “blood pleur-
Drain stay (d)b 7.87 ! 2.03 12.79 ! 2.81 < 0.001 odesis” in 1987. He described the injection of 50 mL of the
patient’s autologous blood into the chest tubes for treatment
Hospital 10.04 ! 2.18 15.04 ! 2.60 < 0.001
of spontaneous pneumothorax after the air leak had sealed
stay (d)b
to prevent recurrence of the pneumothorax. Dumire et al8
Success of the 18 (78.3%) 2 (8.33%) < 0.001
first described the use of the technique to seal an air leak
managementa
from the lung in 1992. Since then, the technique has been
Complications widely used for the treatment of both primary and secondary
Fevera 3 (13.0%) 5 (20.8%) 0.478 pneumothorax.11,13
Pleural 2 (8.7%) 4 (16.7%) 0.413 The exact specific mechanism of action of intrapleural
infectiona instillation of autologous blood is still controversial. It seems

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Deatha 0 0
a
Number (%).
b
Mean ! standard deviation.
and 10.54 ! 3.09 days in group B. The difference between both
groups was highly statistically significant (p < 0.001)
(►Table 2). Time to drain, removal, and duration of hospital
stay were also both significantly shorter in group A than in
group B. The mean time to drain removal ! SD was
7.87 ! 2.03 days in group A and 12.79 ! 2.81 days in group
B (p < 0.001). The mean duration of hospital stays ! SD was
10.04 ! 2.18 days in group A and 15.04 ! 2.60 days in group B
(p < 0.001) (►Table 2). Eighteen patients (78.3%) in group A
and two patients (8.33%) in group B had their air leak stopped
within 7 days from chest drain insertion. All air leaks healed in
all the patients without any other maneuvers, and all patients
were discharged home having had their drains removed.
Three patients in group A (13.0%) and five patients in
group B (20.8%) developed low-grade fever after instillation
of blood, but no organisms were grown from the blood
culture, and no manifestations of drain site infections were
noted, and the temperature settled quickly without treat-
ment. Two patients in group A (8.7%) and four patients in
group B (16.7%) developed empyema which was treated by
pleural drainage and antibiotics. No other complication was
observed and no patients died in either group (►Table 2).
At the out-patient follow-up at 2 and 4 weeks post-
discharge from the hospital, no patient had pneumothorax,
empyema, or any other complication that could be attributed
to the autologous blood-patch pleurodesis.
Discussion
Spontaneous pneumothorax is classified into primary
and secondary. In contrast to primary spontaneous pneu-
mothorax, SSP is associated with underlying lung pathology.
to work by two ways: (1) coagulated blood adheres to the
lung as a patch and seals the air leak directly and (2) blood
causes inflammation and subsequent adhesions between the
lung and pleura, and these adhesions are responsible for
sealing the air leak.8,12
Macchiarini et al16 supposed the ideal sealant as one that
is not immunogenic, allows for expansion, is adherent to the
lung tissue, and should be strong enough to remain sealed.
We would consider that autologous blood will be fulfilling
these criteria. Furthermore, it is an easy to perform, inex-
pensive, and painless bedside procedure.12,17
In our study, the success rate was 78.3% in group A and
8.33% in group B. Rivas de Andrés et al18 treated six persistent
air leak patients with autologous blood with 100% success
24 hours after the procedure. However, Robinson10 only
achieved 85% success with the same treatment in 25 pneu-
mothorax relapse patients. Cagirici et al13 treated 32 patients
with autologous blood, with an 84% success rate.
Unlike chemical pleurodesis, autologous blood-patch can
be successfully used on less than fully expanded lung. In our
study, 16 patients in each group had their lung not fully
expanded at the time of first autologous blood instillation.
This was probably due to its mechanism of action through
patching the defect in the lung parenchyma, rather than
causing true pleurodesis. Ando et al11 reported successfully
treating persistent air leak with autologous blood even with
incomplete lung expansion.
In our study, we compared between early (3 days) intra-
pleural instillation of autologous blood and conservative
management for 10 days before receiving the first intra-
pleural instillation of autologous blood. We found that group
A had a significantly shorter air leak seal, chest drain stay,
and hospital stay duration than group B. Several potential
prospective studies showed that blood pleurodesis had best
outcomes, such as higher success rate, shorter sealing time,
and also fewer complication incidence for persistent air leak,
when compared with conservative strategy.14,17

Thoracic and Cardiovascular Surgeon

 Blood-Patch Pleurodesis for Pneumothorax
A range of blood volumes from 50 to 250 mL was used in
most clinical studies about intrapleural instillation of blood.
These volumes could be injected as a single or repeated
instillations.17,19 We have chosen to use 50 mL, the same
dose described by Dumire et al8 and Cagirici et al.13 Robin-
son’s10 study achieved a high success rate by injecting 50 mL
autologous blood through the chest tube. Our study did not
aim at quantifying blood volume used, but apparently the
quantity we used did not influence our results.
The timing of intrapleural instillation of autologous blood is
controversial. We chose to do the procedure for group A at
day 3 after chest drain insertion to minimize the drain stay and
the hospital stay duration. Rivas de Andrés et al18 suggest
leaving it to the ninth postoperative day. Cao et al20 did the
procedure after 7 days. Other authors suggested doing the
procedure after 5 days.11,14,21 Aihara et al did the procedure
only after 2 days.22
The complications of this procedure, in our study, included
fever (eight patients) and pleural infection (six patients),
which can be attributed to the chest drain itself. However,
the possibility of exacerbating any pleural infection by the
instillation of autologous blood into the pleural cavity needs to
be considered and the procedure should be performed under
strict aseptic technique. No other serious complications were
noted in our study. Other investigators8,9,11 have observed no
harmful effects. Robinson reported pleural infection only in
one patient for an overall incidence of 4%.10
The main limitation of our study was the small sample
size. A larger study is needed to confirm our findings, check
for the optimum timing and volume of blood needed, and
study the complications rate of the procedure.
In conclusion, taking our results into account, we claim that
early intrapleural instillation of autologous blood is compel-
ling and effective for sealing air leak in patients with SSP with
persistent air leak, who are not fit or not willing to have
surgery. It is superior to conservative treatment or late instil-
lation of autologous blood, even if the patients’ lungs were not
fully expanded. This procedure can prompt earlier chest drain
removal and lead to a shorter length of hospital stay. In
addition, we report its safety and good tolerability.
Clinical Registration Number
The clinical registration number is ISRCTN75342605.
References
1 Videm V, Pillgram-Larsen J, Ellingsen O, Andersen G, Ovrum E.
Spontaneous pneumothorax in chronic obstructive pulmonary
disease: complications, treatment and recurrences. Eur J Respir
Dis 1987;71(05):365–371
2 Picado C, Gómez de Almeida R, Xaubet A, Montserrat J, Letang E,
Sánchez-Lloret J. Spontaneous pneumothorax in cryptogenic
fibrosing alveolitis. Respiration 1985;48(01):77–80
Ibrahim et al.
3 Eastridge CE, Hamman JL. Pneumothorax complicated by chronic
steroid treatment. Am J Surg 1973;126(06):784–787
4 MacDuff A, Arnold A, Harvey J; BTS Pleural Disease Guideline
Group. Management of spontaneous pneumothorax: British
Thoracic Society Pleural Disease Guideline 2010. Thorax 2010;
65(Suppl 2):ii18–ii31
5 Milanez JR, Vargas FS, Filomeno LT, Fernandez A, Jatene A, Light
RW. Intrapleural talc for the prevention of recurrent pneu-
mothorax. Chest 1994;106(04):1162–1165
6 Macoviak JA, Stephenson LW, Ochs R, Edmunds LH Jr. Tetracycline
pleurodesis during active pulmonary-pleural air leak for preven-
tion of recurrent pneumothorax. Chest 1982;81(01):78–81
7 Almind M, Lange P, Viskum K. Spontaneous pneumothorax:
comparison of simple drainage, talc pleurodesis, and tetracycline
pleurodesis. Thorax 1989;44(08):627–630
8 Dumire R, Crabbe MM, Mappin FG, Fontenelle LJ. Autologous
“blood patch” pleurodesis for persistent pulmonary air leak. Chest
1992;101(01):64–66
9 Mallen JK, Landis JN, Frankel KM. Autologous “blood patch”
pleurodesis for persistent pulmonary air leak. Chest 1993;103
(01):326–327
10 Robinson CL. Autologous blood for pleurodesis in recurrent and
chronic spontaneous pneumothorax. Can J Surg 1987;30(06):
428–429
Downloaded by: Universite Laval. Copyrighted material.
11 Ando M, Yamamoto M, Kitagawa C, et al. Autologous blood-patch
pleurodesis for secondary spontaneous pneumothorax with per-
sistent air leak. Respir Med 1999;93(06):432–434
12 Rinaldi S, Felton T, Bentley A. Blood pleurodesis for the medical
management of pneumothorax. Thorax 2009;64(03):258–260
13 Cagirici U, Sahin B, Cakan A, Kayabas H, Buduneli T. Autologous
blood patch pleurodesis in spontaneous pneumothorax with
persistent air leak. Scand Cardiovasc J 1998;32(02):75–78
14 Shackcloth MJ, Poullis M, Jackson M, Soorae A, Page RD. Intra-
pleural instillation of autologous blood in the treatment of
prolonged air leak after lobectomy: a prospective randomized
controlled trial. Ann Thorac Surg 2006;82(03):1052–1056
15 Boat TF, Di Sant’ Agnese PA, Warwick WJ, Handwerger SA.
Pneumothorax in cystic fibrosis. JAMA 1969;209(10):1498–1504
16 Macchiarini P, Wain J, Almy S, Dartevelle P. Experimental and
clinical evaluation of a new synthetic, absorbable sealant to
reduce air leaks in thoracic operations. J Thorac Cardiovasc Surg
1999;117(04):751–758
17 Chambers A, Routledge T, Billè A, Scarci M. Is blood pleurodesis
effective for determining the cessation of persistent air leak?
Interact Cardiovasc Thorac Surg 2010;11(04):468–472
18 Rivas de Andrés JJ, Blanco S, de la Torre M. Postsurgical pleurod-
esis with autologous blood in patients with persistent air leak.
Ann Thorac Surg 2000;70(01):270–272
19 Jones NC, Curry P, Kirk AJ. An alternative to drain clamping for
blood pleurodesis. Eur J Cardiothorac Surg 2005;27(05):935
20 Cao Gq, Kang J, Wang F, Wang H. Intrapleural instillation of
autologous blood for persistent air leak in spontaneous pneu-
mothorax in patients with advanced chronic obstructive pulmon-
ary disease. Ann Thorac Surg 2012;93(05):1652–1657
21 Oliveira FH, Cataneo DC, Ruiz RL Jr, Cataneo AJ. Persistent pleur-
opulmonary air leak treated with autologous blood: results from a
university hospital and review of literature. Respiration 2010;79
(04):302–306
22 Aihara K, Handa T, Nagai S, et al. Efficacy of blood-patch pleurod-
esis for secondary spontaneous pneumothorax in interstitial lung
disease. Intern Med 2011;50(11):1157–1162
Thoracic and Cardiovascular Surgeon