CONCISE DEFINITIVE REVIEW

Jonathan E. Sevransky, MD, MHS, Series Editor

Bronchopleural Fistula in the Mechanically

Ventilated Patient: A Concise Review
John C. Grotberg, MD1
OBJECTIVE: To describe the physiology of air leak in bronchopleural
Robert C. Hyzy, MD2
fistula in mechanically ventilated patients and how understanding of its
Jose De Cardenas, MD2
physiology drives management of positive-pressure ventilation. To pro-
vide guidance of lung isolation, mechanical ventilator, pleural catheter, and Ivan N. Co, MD2
endobronchial strategies for the management of bronchopleural fistula on
mechanical ventilation.
DATA SOURCES: Online search of PubMed and manual review of arti-
cles (laboratory and patient studies) was performed.
STUDY SELECTION: Articles relevant to bronchopleural fistula, mechan-
ical ventilation in patients with bronchopleural fistula, independent lung
ventilation, high-flow ventilatory modes, physiology of persistent air leak,
extracorporeal membrane oxygenation, fluid dynamics of bronchopleu-
ral fistula airflow, and intrapleural catheter management were selected.
Randomized trials, observational studies, case reports, and physiologic
studies were included.
DATA EXTRACTION: Data from selected studies were qualitatively evalu-
ated for this review. We included data illustrating the physiology of driv-
ing pressure across a bronchopleural fistula as well as data, largely from
case reports, demonstrating management and outcomes with various ven-
tilator modes, intrapleural catheter techniques, endoscopic placement of
occlusion and valve devices, and extracorporeal membrane oxygenation.
Themes related to managing persistent air leak with mechanical ventilation
were reviewed and extracted.
DATA SYNTHESIS: In case reports that demonstrate different approaches
to managing patients with bronchopleural fistula requiring mechanical ven-
tilation, common themes emerge. Strategies aimed at decreasing peak
inspiratory pressure, using lower tidal volumes, lowering positive end-
expiratory pressure, decreasing the inspiratory time, and decreasing the
respiratory rate, while minimizing negative intrapleural pressure decreases
airflow across the bronchopleural fistula.
CONCLUSIONS: Mechanical ventilation and intrapleural catheter man-
agement must be individualized and aimed at reducing air leak. Clinicians
should emphasize reducing peak inspiratory pressures, reducing positive
end-expiratory pressure, and limiting negative intrapleural pressure. In re-
fractory cases, clinicians can consider lung isolation, independent lung ven-
tilation, or extracorporeal membrane oxygenation in appropriate patients as
well as definitive management with advanced bronchoscopic placement of Copyright © 2020 by the Society of
valves or occlusion devices. Critical Care Medicine and Wolters
Kluwer Health, Inc. All Rights
KEY WORDS: bronchopleural fistula, mechanical ventilation, alveolar-
Reserved.
pleural fistula, independent lung ventilation, intrapleural catheter
DOI: 10.1097/CCM.0000000000004771

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B
ronchopleural fistula (BPF) is defined as a con-
nection between the pleural cavity and bronchus
with persistent air leak. Technically, alveolar-
pleural fistula refers to air leak originating from lung
parenchyma but is also commonly referred to as “BPF.”
The duration of persistent air leak defining BPF ranges
from 24 hours to 5 days, though more than 24 hours,
is generally accepted (1–3). Lung resection remains the
leading cause of a true BPF with prevalence ranging
from 4.5% to 20% after pneumonectomy and 0.5% to 1%
after lobectomy (1, 2, 4). Additional etiologies, generally
alveolar-pleural in nature, include mechanical ventila-
tion, pulmonary trauma, spontaneous pneumothorax,
acute respiratory distress syndrome (ARDS), iatrogenic
injuries, radiation, radiofrequency ablation, and inva-
sive infectious or inflammatory etiologies (2, 4).
In mechanically ventilated patients, BPF commonly
is the result of a pneumothorax. This occurs by direct
disruption of airway or visceral pleura or by sponta-
neous alveolar rupture. Once pneumothorax develops
in a mechanically ventilated patient, the pleural space
should be evacuated by tube thoracostomy to prevent
tension pneumothorax. Air leak persisting beyond 24
hours confirms a diagnosis of BPF.
BPF in the mechanically ventilated patient is associ-
ated with high morbidity and mortality (1, 2, 5). A re-
view of 1,700 mechanically ventilated patients found
that 2% had BPF secondary to barotrauma or direct lung
injury with an overall mortality of 67%. Others have re-
ported mortality ranging from 27.2% to 50% (5–7). Late
onset of BPF (> 24 hr of mechanical ventilation) and air
leak greater than 500 mL per breath were associated with
increased mortality (5). Epidemiology of BPF is predom-
inantly from an era when it was common to deliver large
tidal volumes (8). In randomized controlled trials com-
paring high and low tidal volumes in ARDS, the com-
posite prevalence of barotrauma was 11.4% compared
with 9.6%, respectively (8–14). Presumably, the preva-
lence of BPF as a complication of mechanical ventilation
in critically ill patients is likely lower than that previously
reported. Consequently, the management of mechani-
cally ventilated patients with BPF is less familiar to inten-
sivists in the era of lung-protective ventilation.
IDENTIFYING AIR LEAK IN
MECHANICALLY VENTILATED PATIENTS
Clinical manifestations of BPF in the mechan-
ically ventilated patient may include the loss of
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Concise Definitive Review
positive end-expiratory pressure (PEEP), resulting in
hypoxemia, loss of effective tidal volume, worsening of
ventilation-perfusion mismatch, and persistent subcu-
taneous emphysema, pneumomediastinum, or pneu-
mopericardium. Bubbling in the water seal of a chest
drainage device, once a pleural drain is placed, is seen
for more than 24 hours. Chest tube suction may in-
crease flow across the fistula, leading to poor gas ex-
change and BPF healing. In volume-cycled modes, air
leak can be directly measured as a difference between
the inspiratory and expiratory volumes in the ventilator
circuit. There is little consensus defining large versus
small air leaks. Qualitative grading systems based on
the timing of leak during the respiratory cycle versus
quantification with digital chest drainage systems or
air leak meters can be used (15–20). Confirmation of
the presence of bubbling in the drainage system, cor-
rect pleural placement of the chest tube, secure con-
nections, and an inflated endotracheal tube cuff will
differentiate leak from BPF compared with leak from
the ventilator circuit (8, 21).
Evidence of air leak can also be observed in venti-
lator waveforms. Total volume, represented by the area
under the flow curve, will be greater in inspiration
than in expiration, indicating volume loss between in-
spiratory and expiratory cycles. The volume tracing
also will not return to baseline, indicating volume loss
(Fig. 1) (22, 23).
PHYSIOLOGY OF AIR LEAK AND
POSITIVE-PRESSURE VENTILATION
Ventilator management to minimize air leak and op-
timize gas exchange derives from understanding the
physiologic mechanisms of BPF airflow. Laminar flow
through a BPF is an interaction of visceral pleural de-
fect size, local lung compliance, airway pressure, relative
airway resistance, and transpulmonary pressure (24).
Volumetric flow of BPF air leak BPF (FBPF ) is propor-
tional to mean airway pressure (P AW ) (Fig. 2A) (25–27).
Transpulmonary pressure as a difference in P AW and
pleural pressure (PPL ) represents the driving pressure
between the pulmonary airways and the BPF (Table 1).
Peak-inspiratory pressure (PIP) and PEEP both con-
tribute to P AW . In animals, some have shown that the
effect of increasing PEEP led to increased air leak com-
pared with increasing PIP, whereas others have shown
that flow was directly proportional to P AW despite
alterations in PIP and PEEP (28–30). Interestingly,
Grotberg et al
Figure 1. Detecting air leak from bronchopleural fistula by
ventilator waveform analysis. A, Tracing of flow over time in
seconds, showing the area under the curve (tidal volume) is
smaller during exhalation. B, Tracing of pressure over time in
seconds. C, Tracing of volume over time in seconds. Figure
adapted from Lucangelo et al (22) with permission.
increasing P AW also led to not only increasing airflow
but also increasing BPF resistance, indicating that
increased driving pressure between the pulmonary
airways and pleura results in increased air leak despite
higher resistance (31). Data are limited in humans
illustrating these physiologic determinants. However,
a case report demonstrated that volume loss through
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Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
a BPF increased from 15% to 54% with the addition
of 15 cm H2O of PEEP illustrating the significant con-
tribution of PEEP to P AW (32). This understanding is
critical to minimize BPF flow, improve gas exchange,
and reduce mortality with mechanical ventilation.
CONVENTIONAL MECHANICAL
VENTILATION
Understanding BPF physiology allows for the ma-
nipulation of key variables with the ventilator to help
minimize and/or heal BPF as well as manage patients’
ventilator needs. Specifically, alterations in the vari-
ables that determine P AW can improve BPF air leak
and reduce mortality. This includes decreasing PIP by
using lower tidal volumes (generally 4–6 or 3–4 cc/kg
for single-lung or independent lung ventilation [ILV]),
lowering PEEP, decreasing the inspiratory time, and
decreasing the respiratory rate (Table 2) (2, 33, 34).
Permissive hypercapnia should be considered in
patients with high-minute ventilation requirements, as
these strategies may affect gas exchange. There is little
evidence demonstrating the superiority of one mode
over another. Intermittent mandatory ventilation and
pressure support ventilation have been proposed to
have theoretical advantage in reducing mean airway
pressures by supporting spontaneous ventilation
though comparative data are lacking (25).
LUNG ISOLATION
In patients where adjusting conventional mechanical
ventilation variables proves unsuccessful, advanced
techniques can be used. Lung isolation anatomically
separates the left and right lungs to achieve one lung
ventilation (35). In BPF, isolating the lung contralateral
to the BPF will stop air leak and promote wound heal-
ing of the fistula site. In patients with large, proximal
fistulas, a large air leak may affect the ability to ade-
quately oxygenate and ventilate contralateral lung pa-
renchyma. In this case, isolating the contralateral lung
may improve gas exchange, while eliminating air leak
across the BPF.
There are numerous techniques for lung isolation,
including endobronchial blockers, double lumen en-
dotracheal tube (DLT), and modified single lumen
tubes (Fig. 3). Approach should be catered to the in-
dividual patient and may depend on the tolerability of
single-lung ventilation, laterality of the fistula, patient
 Concise Definitive Review

Figure 2. Management of the pleural space in bronchopleural fistula (BPF). A, Illustration of driving pressure between pulmonary
airways and the intrapleural space through a BPF. Flow is proportional to P AW − PPL . B, Illustration of driving pressure between pulmonary
airways and the intrapleural space through a BPF. Flow is proportional to P AW − PPL . Illustration of mechanism to apply positive
intrapleural pressure. Exhaled gas passes through an exhalation valve through large-bore tubing to a positive end-expiratory pressure
(PEEP) device. Intrapleural gas passes through a chest tube drainage system and is connected to the PEEP device by an evacuation
port with an intrapleural pressure gauge. Figure adapted from Downs and Chapman (78).

TABLE 1. anatomy, and the consideration of other ventilation

techniques. There is no difference in placement ability
Quantitative Drivers of Bronchopleural
Fistula Flow or complications between right-sided and left-sided
DLTs when compared with endobronchial block-
Equations Governing Bronchopleural Fistula ers (35–39). DLT have the advantage of easy conver-
Air Leak
sion into ILV, if needed. Sedation and neuromuscular
  blockade are often required to maintain correct posi-
1.  P AW = 1 (PIP − PEEP )  TI  + PEEP
2 T  TOT
tion for DLTs.
Although not constituting lung isolation per se,
2.  FBPF = ( P AW − PPL )πRBPF
4
there may also be benefit in positioning the patient in
8 µL
the lateral decubitus position with the BPF side down.
3.  PTP = P AW − PPL In a case report, this has been shown to decrease BPF
leak by reducing airflow to the affected lung secondary
4.  FCT = π r P
2 5
to regional differences in the intrathoracic intra-
fL abdominal pressure gradient. Positive pressure pref-
erentially displaces the diaphragm in nondependent
Equation 1: Mean airway pressure (P AW ) as function of peak
lung zones (40).
inspiratory pressure, positive end-expiratory pressure, inspiratory
time (TI), and total respiratory cycle time (TTOT).
Equation 2: Volumetric flow across bronchopleural fistula (FBPF) as
a function of mean airway pressure (P AW ), pleural pressure (PPL),
ENDOBRONCHIAL MANAGEMENT
radius of the bronchopleural fistula (RBPF), viscosity of air (µ ), and Endobronchial management with occlusive materials
bronchopleural fistula length (L).
or endobronchial valves may be considered to reduce
Equation 3: Transpulmonary pressure (PTP) as a function of mean
airway pressure (P AW ) and pleural pressure (PPL). air leak. In the cases of small (< 5 mm) BPFs, where
Equation 4: Turbulent flow through a chest tube (FCT ) as a func- the defect is observed by bronchoscopy, occlusive
tion of radius (r), pressure (P), friction factor (f), and length (L). materials could mechanically seal the leak. Occlusive

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Grotberg et al

TABLE 2.
Strategies to Decrease Mean Airway Pressure and Bronchopleural Fistula Leak Using
Conventional Modes of Mechanical Ventilation and Strategies to Decrease Driving Pressure
Across a Bronchopleural Fistula Resulting in Decreased Bronchopleural Fistula Air Leak
Strategies for Intrapleural
Strategies for Mechanical Ventilation Catheter Management

Low peak-inspiratory pressures (< 30 cm H2O)

Low tidal volume (4–6 and 3–4 cc/kg for single-lung ventilation) Limit negative intrapleural pressure
Set chest tube to water seal
Lowest possible PEEP Positive intrapleural pressure
Minimize inspiratory time   Intrapleural pressure < PEEP
Low respiratory rate   Intrapleural pressure = PEEP
Allow for permissive hypercapnia
Consider independent lung ventilation or lung isolation
PEEP = positive end-expiratory pressure.

substances have included glutaraldehyde sterilized
lead, gel foam and tetracycline, fibrin glue, gelatin-
resorcinol mixture, oxidized regenerated cellulose,
albumin-glutaraldehyde, cryoprecipitate fibrin, and
autologous blood patch (41–46). With more proximal
tracheal or bronchial defects, airway stents might be
used. Amplatzer devices have previously been em-
ployed to occlude larger tracheobronchial defects;
however, there is risk of dislodgement into the pleural
space, or more proximal airways, leading to airway

Figure 3. Airway and endobronchial management in bronchopleural fistula. A, Image of an endobronchial blocker passed through an
endotracheal tube. B, Diagram of endobronchial blocker occluding the left mainstem bronchus. C, Chest radiograph demonstrating
left apically directed chest tube (arrow). D, Bronchoscopy demonstrating endobronchial balloon occlusion of the apical segment of
the right lobe resolving bronchopleural fistula air leak. E, Image of double lumen endotracheal tube (DLT). F, Diagram of double lumen
endotracheal tube connected to two ventilators. G, Chest radiograph demonstrating DLT placement in a patient with bronchopleural
fistula. H, Placement of two endobronchial valves (Spiration, Redmond, WA) in the apical and anterior segments of the right upper lobe
(arrows).

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obstruction (47–49). Most of these interventions are
restricted to cases series. In the cases where the defect
is localized in the visceral pleural and beyond reach
of the bronchoscope, selective endobronchial sealing
can be achieved with one-way endobronchial valves.
Originally designed for endoscopic lung volume re-
duction, the valves allow airflow out of bronchial seg-
ments/subsegments, while preventing distal airflow
(50–56). Success depends on the presence of a com-
plete fissure in the affected lung, sometimes even if the
fissure is not complete, the air leak in the chest tube
will decrease enough to allow transition to water seal.
In a case series of nonsurgical candidates with ARDS
and persistent air leak, endobronchial valve placement
resolved the air leak and resulted in decreased venti-
lator days (57). Liberation from mechanical ventilation
using endobronchial valves has also been reported in
nonARDS patients (58).
Methods to locate the region of air leak broncho-
scopically include the balloon-occlusion method and
the Chartis system (Pulmonx, Redwood City, CA). The
more commonly used balloon-occlusion method uses a
Fogarty balloon (Edwards, Irvine, CA) catheter, which
is sequentially inflated in the lobar bronchi. Cessation
or significant decrease of air leak in the pleural drain-
age system following occlusion of a lobar bronchus
identifies that leading to the fistula. The Chartis system
was originally designed to detect collateral ventilation
and uses a balloon catheter with a flow and pressure
sensor and is not commonly used in mechanically ven-
tilated patients (51, 59).
INDEPENDENT LUNG VENTILATION
In refractory cases, the ventilator strategies that reduce
BPF leak may result in suboptimal gas exchange. ILV
allows maintaining low airway pressures ipsilateral to
the BPF, while facilitating optimal ventilation of the
contralateral lung, using a DLT and two ventilators
(Fig. 3). Ventilatory support with ILV can be performed
synchronously or asynchronously. In synchronous ILV,
the respiratory rate to each lung is identical, whereas
tidal volume, inspiratory flow, PEEP, and Fio2 are al-
tered to optimize gas exchange. Asynchronous ILV
employs all different variables, including ventilatory
mode (60). ILV is typically resumed until persistent air
leak has resolved, tidal volume differential is less than
100 mL, and lung compliance differential is less than
20% (61). Case series demonstrate the effectiveness of
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Concise Definitive Review
ILV in patients who cannot tolerate airway pressures
required to minimize air leak (60, 62–68).
HIGH-FREQUENCY VENTILATION
High-frequency ventilatory modes have been evalu-
ated for managing patients with refractory air leak.
Tidal volumes of 2–5 mL/kg are delivered at 100–200
breaths/min. Mechanisms of gas exchange include
bulk flow, augmented Taylor dispersion, the Pendelluft
effect, gas profiling, molecular diffusion, and cardio-
genic mixing.
The evidence using high-frequency ventilatory
modes in the management of adult patients with BPF
is both varied and controversial. Case reports have
demonstrated improvement in gas exchange and BPF
leak with high-frequency jet ventilation and high-fre-
quency oscillatory ventilation (HFOV) (25, 30, 69–72).
However, a case series of patients with acute respira-
tory failure and BPF randomized to conventional me-
chanical ventilation or HFOV reported that six of seven
patients deteriorated with HFOV. In patients with oth-
erwise normal lung parenchyma, airway impedance
drives the distribution of gas flow. HFOV increases
airway impedance, thus reducing flow across a BPF.
However, in patients with diminished lung compliance,
the increase in airway impedance with HFOV has less
of an effect on the distribution of gas flow (73). Due
to varying evidence, high-frequency modes in me-
chanically ventilated patients with BPF are not recom-
mended as an initial strategy. Selective patients may
benefit; however, caution should be taken in patients
with poor lung compliance.
INTRAPLEURAL CATHETER
MANAGEMENT
Pleural drainage plays a key role in the management
of BPF, as it evacuates air from the pleural space and
controls a potential source of infection. Turbulent flow
through the chest tube is governed by the Fanning
equation (Table  1). A correctly placed, fully patent
14-Fr pleural pigtail, with applied –20 cm H2O of suc-
tion, can evacuate approximately 12.8 ± 0.3 L/min.
Inability to achieve lung expansion should lead to the
clinician to evaluate correct location and patency of
the tube, possibility of nonexpandable lung, or pres-
ence of large air leaks (> 16 L/min) and, therefore, in
the latter scenario, a larger chest tube (74).
Grotberg et al
Similar to controlling P AW with the ventilator, PPL can
also be manipulated to decrease BPF driving pressure
(Table  2). For example, transitioning chest tube from
suction to water seal resolved persistent air leak in 60%
of postoperative patients (15, 75). Randomized trials
have shown that in patients undergoing lung resection, a
“shorter” period of chest tube suction followed by water
seal can reduce air leak and chest tube duration in patients
without clinically significant pneumothorax (18, 75–77).
There is some historic evidence to support posi-
tive pressure with intrapleural catheters (26, 78–80).
Although one case series had success setting intrapleu-
ral pressure equal to PEEP, others found this leads to
significant pneumothorax (78). Expiratory transpulmo-
nary pressure can be calculated, and intrapleural pres-
sure titrated to allow for significant reduction in BPF
flow while maintaining adequate lung expansion (79).
In the past, positive intrapleural pressure was delivered
by routing exhaled gas to a PEEP device connected to
the pleural drainage system (Fig. 2B) (78, 79).
Despite limited prospective, randomized trials, cur-
rent evidence would suggest that there is a role for
manipulating intrapleural pressure to reduce or elimi-
nate persistent air leak. Excessive negative intrapleural
pressure should be avoided, and the addition of posi-
tive intrapleural should be reliant on a patient’s indi-
vidual physiology. Clinicians should monitor patients
closely for development of tension pneumothorax and
intrapleural infections if chest tubes are set to water
seal or positive intrapleural pressure.
EXTRACORPOREAL MEMBRANE
OXYGENATION
In patients with BPF and refractory ventilatory failure,
veno-venous-extracorporeal membrane oxygenation
(VV-ECMO) promotes gas exchange while permitting
ultralung protective ventilation. ECMO may allow for
BPF healing and fistula closure or may provide a bridge
to definitive intervention. Case reports have illustrated
the success of ECMO in BPF (67, 81–83). A case se-
ries of patients with traumatic BPF using VV-ECMO
as primary therapeutic intervention showed cessa-
tion of air leak after cannulation with ultralung pro-
tective ventilation with adherence to the ECMO for
protective ventilation protocol (83–85). Venoarterial
ECMO (VA-ECMO) has also been used in postoper-
ative patients unable to undergo primary BPF closure.
In a case series of five patients with massive air leaks
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(> 5 mL/kg), VA-ECMO led to BPF closure in three of
five patients (81).
CONCLUSIONS
Intensivists may care for patients with BPF while on
mechanical ventilation. Management to decrease air
leak and improve gas exchange requires a robust un-
derstanding of the physiology driving air leak. These
principles are well demonstrated in animal models
with some supportive clinical evidence in bedside
management with the overarching goal of diminish-
ing driving pressure across the fistula. The strongest
evidence promotes the emphasis of reducing P AW by
decreasing tidal volumes to reduce PIP and more im-
portantly by decreasing PEEP, though decreasing in-
spiratory time and respiratory rate are also beneficial
with conventional modes. Clinical evidence varies
with respect to pleural pressure management, how-
ever, limiting negative intrathoracic pressure, as per-
mitted by maintaining lung expansion, is the initial
strategy to decrease BPF driving pressure. BPF size,
location, etiology, chronicity, and presence of low lung
compliance will affect a patient’s physiology on the
ventilator and the ability to tolerate pleural pressure
manipulation with respect to BPF leak. The approach
to management should, therefore, be tailored to the
individual patient. Clinicians may also consider endo-
bronchial management. In refractory cases, clinicians
should consider lung isolation, ILV, and ECMO in ap-
propriate patients.
1 Department of Internal Medicine, University of Michigan,
Ann Arbor, MI.
2 Department of Pulmonary and Critical Care Medicine,
University of Michigan, Ann Arbor, MI.
Work for this study was performed at the University of Michigan
Hospital.
The authors have disclosed that they do not have any potential
conflicts of interest.
Address requests for reprints to: John C. Grotberg, MD, 3116
Taubman Center, SPC 5368 1500 E, Medical Center Drive, Ann
Arbor, MI 48109. E-mail: grotberj@med.umich.edu
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