Bronchopleural fistula (BPF) is a pathological communication between the bronchial tree and pleural space. This clinical condition, which has high mortality and morbidity, is one of the major therapeutic challenges for clinicians even today. BPF may result from a lung neoplasm, necrotizing pneumonia, empyema, blunt and penetrating lung injuries, and a complication of surgical procedures. Lung resection is the most common cause of BPF, and this chapter will focus more on this topic. Frequency ranges from 4.5 to 20% after pneumonectomy and from 0.5 to 1% after lobectomy. Several risk factors have been defined in the development of postoperative BPF; preoperative radiotherapy, pulmonary infection, diabetes, right pneumonectomy, a long bronchial stump, residual cancer at the stump (R1 and R2 resection), and the need for postoperative ventilation (especially with high PEEP). BPFs are divided, based on the time elapsed since surgery, into early or late fistula. This grouping is important in management of patient treatment. In early BPF, surgical treatment is generally the preferred treatment modality, whereas in late BPF, conservative approach is preferred. The management of BPF is still one of the most complex challenges encountered by the thoracic surgeons; so prevention is the best way to manage postoperative BPF.
- bronchopleural fistula
- lung resection
Bronchopleural fistula (BPF) has been defined as a direct communication between the bronchus and pleural cavity. Some authors have grouped BPFs as central and peripheral according to their locations . While a central BPF defines connection between pleura and tracheobronchial three, a peripheral BPF defines connection between the pleura and airway distal to segmental bronchi or lung parenchyma. In literature, the term of “alveolopleural fistula” is also used to describe peripheral BPFs.
Nonsurgical conditions like trauma, chronic necrotizing pneumonia, empyema, radiotherapy, bulla, or cyst rupture can cause BPF, but the most common cause is lung resection. Frequency ranges from 4.5 to 20% after pneumonectomy and from 0.5 to 1% after lobectomy. BPF-related mortality ranges from 18 to 71% in the literature [2, 3, 4]. Because of high morbidity and mortality rates, it is important to define risk factors and apply preventative methods especially in groups of risky patients.
Many authors have divided postoperative BPFs into two groups according to time of onset. There is no consensus about these definitions in the literature, but generally, early BPF was defined as fistula occurring within 30 days after the initial operation. Late BPF was defined as fistulas occurring after more than 30 days. It is established that early BPFs are most commonly associated with a failure in surgical technique and mostly, it can be repaired with reoperation [1, 3, 5].
Late BPFs are typically secondary to patient-related factors and almost always coexist with empyema, and it usually required complex, long-term, and exhausting treatment process for both the patient and the surgeon.
2. Risk factors
BPF is most commonly encountered after lung resections; therefore, establishing risk factors is important to prevent patients from this highly mortal complication.
Numerous risk factors have been associated with BPF development in the literature [3, 4, 5, 6]. We divided these risk factors into three groups: patient-related factors, surgeon-related factors, and anatomic factors.
Age (>60), gender (male), neoadjuvant radiation therapy, diabetes mellitus, malnutrition, smoking, chronic steroid/immunosuppressive usage, and need for postoperative mechanic ventilation can be classified as a patient-related risk factor. Induction chemotherapy has been cited as a risk factor for postpneumonectomy BPF but there is not any increased risk for bronchoplastic procedures.
A large number of studies have reported an increased risk for BPF due to postoperative mechanical ventilation usage after pneumonectomy. Therefore, to prevent bronchial stump from barotrauma extubation must be achieved at the earliest time after surgery.
A low forced expiratory volume in 1 second and low carbon monoxide diffusing capacity were also defined as risk factors for postoperative BPF occurrence.
Besides these patient-related risk factors, several anatomic disadvantages were defined for right-sided pneumonectomy:
According to cadaveric studies, presence of two left-sided and one right-sided bronchial artery supply is the most common configuration.
While the left main bronchus is protected under the aortic arch and surrounded by mediastinal tissue, the right bronchial stump has no such coverage.
The right main bronchus is wider, and more vertical than the left main bronchus. This condition facilitates secretion retention on the right main bronchial stump.
Early BPFs are usually related with technical failure during surgery. The most common causes of this condition are poorly secured knots, stapler misfiring, and high anastomotic tension. Other surgeon-related risk factors are extensive mediastinal lymphadenectomy and peribronchial dissection, long bronchial stump and not coverage the bronchial stump with viable tissue.
3. Clinical presentations and diagnosis
The size and the time of occurrence of the BPF are major determinants of the clinical presentation but, patients often have infection-related symptoms like: fever, cough with serosanguinous or purulent sputum, night sweats, and chills.
Expectoration and respiratory symptoms typically worsen with the patient lying on the side opposite to the one involving the fistula. Flooding of the infected contents of the pleural space to the contralateral lung can lead to severe pneumonia or respiratory distress syndrome.
If the patient has a chest tube massive and prolonged air leakage would be an important clinical clue for BPF.
White blood cell count and systemic inflammation markers are often elevated.
Chest radiogram often revealed a decrease in the fluid level and enlargement in the ipsilateral pleural cavity. Due to the contamination of the contralateral lung by the infected content of the pleural cavity, parenchymal infiltration can be seen.
Computed tomography of the chest can depict mediastinal emphysema, parenchymal infiltration, and enlargement of the pleural cavity, but its success at demonstrating the presence of the BPF is controversial. By the imaging of the continuation of a bronchus or the lung parenchyma to the pleural space, definitive diagnosis of the fistula can be made (Figures 1 and 2). Westcott et al. reported sensitivity of the chest CT as 50% at demonstrating the presence of the peripheral BPFs. Seo et al. reported that chest CT succeed to demonstrate direct or indirect signs of BPF 86% of the patients with central, and 100% of the patients with peripheral BPFs [7, 8].
In the presence of clinical or radiological suspicion of BPF, bronchoscopy must be applied to examine the bronchial stump. Presence of pleural fluid leakage or/and air bubbling in the bronchial stump is pathognomonic (Figures 3 and 4).
Reconstruction of 2-dimensional, helical CT images provides noninvasive intraluminal evaluation of the bronchus named as “virtual bronchoscopy” . This technique can provide additional benefits, especially, planning endobronchial instrumentation, but it is not an essential diagnostic method of fistula.
Less frequently 133xenon or 99technetium ventilation scintigraphy can be used to identify BPF by visualization of the radioactive isotopes in the empty pleural cavity. Mark et al. used 99technetium ventilation scintigraphy in 28 postpneumonectomy patients for the detection of BPF and reported sensitivity of 78% and a specificity of 100% [10, 11]. Although, this is a noninvasive diagnostic procedure, it is not practical and easy-to-use, and has no additional benefit to the detection of underlying lung disease.
The management of the BPF needs prolonged hospitalization, complex surgical procedures, and close follow-up, but first step in the treatment is management of the life-threatening conditions like sepsis, tension pneumothorax, and respiratory failure. Protection of the contralateral lung from aspiration of the pleural fluid is important to reduce the risk of pneumonia and respiratory failure. Therefore, chest tube must be applied to ensure the drainage of the pleural cavity. Broad spectrum antibiotic therapy against Gram-Positive, Gram-Negative, and anaerobic microorganisms must be initiated, and it should be tailored based on the results of culture-antibiograms.
Early BPFs are mostly associated with failure in the surgical technique. Repairment of the bronchial stump with re-operation is the best treatment modality in these patients.
Patients with late BPF mostly have poor medical condition and major surgical approaches cannot be applied. Conservative treatment modalities like drainage and reduction of the pleural space, pleural irrigation, antibiotics, and nutritional supplementation. Boudaya et al. reported their experience with conservative management of postresectional BPF in 17 patients and BPF is successfully closed in 16 patients .
Various endoscopic techniques for the control of small BPFs have been reported, especially in patients with poor condition. Sealants, fibrin glue, coils, and endobronchial silicon or metal stents have been used to treat small BPFs (ranging from 0.8 to 1.0 mm). Dutau et al. used self-expanding metal stents in seven patients with large fistulas (>6 mm) and reported improvement in patients’ respiratory parameters in early postoperative period .
4.1 Surgical interventions for infection control
Besides conservative treatments, several surgical procedures to treat BPFs have been defined in the literature. Main objectives in these surgical interventions are debridement of the pleural space, minimizing the residual pleural cavity, closure of the fistula, and reinforcement of the bronchial stump with autologous tissue.
There are several factors in choosing the appropriate surgical method:
Medical condition of the patient
Time of onset of the fistula
Size and localization of the fistula
State of the pleural cavity
4.1.1 Video-assisted thoracoscopic surgery (VATS)
In the presence of pleural infection together with the fistula, tube-thoracostomy must be applied in all cases. Pleural irrigation with antibiotic and povidone-iodine solutions is suggested in sterilization of the infected postpneumonectomy pleural cavity but this treatment modality alone cannot provide sufficient debridement, especially in patients with late fistulas and cause prolong hospitalization.
VATS is a useful method to obtain drainage and debridement of the infected pleural cavity. Single port is usually sufficient in most cases; material and debris can be safely removed with surgical instruments and in the presence of small BPFs (<3 mm) fibrine glue can be applied. Hollaus et al. applied videothoracoscopic debridement in nine patients and defined it as an efficient method to treat postpneumonectomy empyema . Gossot et al. reported series of 11 patients with postpneumonectomy empyema. These 11 patients underwent videothoracoscopic debridement and 8 of 11 patients discharged without need of additional surgical procedures . These similar studies have shown that VATS is a feasible option for treatment in select patients with PPE and small BPF.
4.1.2 Open window thoracostomy
In the presence of empyema drainage of the pleural cavity is essential to control the septic status of the patient. Different kinds of drainage techniques were defined in the literature. Open-window thoracostomy was first described by Robinson in 1916 in patients with nontuberculous empyema and Eloesser has revised this procedure for patients with tuberculous empyema [16, 17]. This procedure contains:
Segmental resection of 2–3 ribs
Creation of a skin flap (Muscle should be preserved if possible)
Marsupialization of the cavity
With this procedure, epithelialized thoracostomy window is obtained and effective drainage is ensured.
After this operation, the wound is packed at least daily with gauze moistened with normal saline. Granulation tissue in the wound begins to form over time and when the pleural space is clean closure of the window can be considered.
It is very important to have a good cooperation with patient and relatives for this treatment modality and they should be informed that this treatment procedure may require several weeks.
4.1.3 Clagett procedure
Clagett and Geraci described a two-step treatment technique for the management of postpneumonectomy empyema in 1963 . Step 1 contains the open window thoracostomy to drain the septic cavity. Step 2 contains obliteration of the pleural cavity with antibiotic solution. Pairolero and Arnold has modified this procedure and described transposition of a well-vascularized extrathoracic muscle as an intermediate step . With this modification, further reinforcement of the bronchial stump was ensured.
Clagett procedure shows a success rate (OWT closed without PPE recurrence) of 61–89% with a mortality rate between 0 and 24% in the literature.
4.2 Surgically closure of a bronchopleural fistula
Large BPF can cause loss in the tidal volume, aspiration of infected pleural fluid, and respiratory distress. Therefore, bronchial defect must be controlled, especially in patients with large fistulas, for this purpose, two major approaches were defined in the literature.
4.2.1 Transpleural approach
Transpleural approach is the most common method to closure of the BPF (Figure 5). First, BPF must be identified. By careful dissection, bronchus must be mobilized as close to the carina as possible to provide adequate length. Aggressive dissection and devascularization of the proximal bronchus should be avoided because of the risk of failure of the repair and recurrence of BPF. Stapler devices can be used if there is a sufficient length in the bronchial stump. Manual suturation also can be applied above the BPF. After repairment, bronchial stump must be buttressed with well-vascularized tissue such as extrathoracic muscle, omentum, or diaphragm flap.
4.2.2 Transsternal transpericardial approach
In some cases, surgical management of BPF may be challenging through a lateral transpleural approach. Presence of short bronchial stumps, left-sided BPF, necrotic bronchial stumps and/or history of prior BPF closures via thoracotomy are the main reasons that make transpleural approach difficult. In these cases, transsternal transpericardial approach would be a good alternative to transpleural approach [20, 21]. This approach provides work in healthy, inflammation-free planes. Therefore, in this technique, isolation of the airway is easier and safer than others. Biggest benefit of this technique is that it provides the opportunity to work in a healthy plane. Retraction of the superior vena cava and aorta laterally provide sufficient exposure to make a successful repairment. It is also possible to achieve transpericardial approach by anterior thoracic incision with division of multiple costal cartilages which was described by Padhi and Lynn . This approach was found to be a difficult and complicated compared to transsternal approach. Therefore, transsternal transpericardial approach has become more widely used among surgeons in the repairment of BPF.
One of the major concerns in the treatment of the BPF is obliteration of the persistent space after control of pleural infection. Thoracoplasty is originally considered as a treatment for active tuberculosis but this procedure is also functional for obliterate pleural space with the viable tissue of the chest wall in the cases of BPF. This is achieved by resection of multiple ribs. Traditional thoracoplasty requires removal of the first 11 ribs periosteum, and intercostal muscles with associated neurovascular bundles. After removal of these structures, skin and thoracic muscles fill the pleural cavity. As can be expected, this procedure has high mortality and morbidity rates and is now abandoned. Removing fewer than five ribs named as “tailored” thoracoplasty is still in use especially in the treatment of chronic BPFs [23, 24].
It would be rational to use these treatment modalities in combination to deal with space problem. Tailored thoracoplasty, muscle transposition, omentoplasty, and diaphragm flabs can be used and combined with each other. Clinical condition and performance status of the patient are also important for selection of the best method in the treatment of BPF.
5. Bronchoscopic management of BPF
Various endoscopic techniques like bronchoscopic application of sealants, fibrin glue, silver nitrate cautery, coils, and endobronchial stents for the control of small BPFs have been reported [25, 26, 27, 28, 29]. There is no consensus on which method is most effective for BPF closure. We use endoscopic techniques only for the patients with poor clinical condition and not for proper major surgical intervention. Proper technique must be selected depending on the length of the bronchial stump, the location, and size of the fistula (Figures 6 and 7).
We often prefer metallic J-stents and silicon Y-stents (Figure 8). The most seen complication of these stents is migration and occlusion with secretion. Migration and occlusion of the stent can cause severe respiratory distress. Retention of the secretion can also cause contamination of the remaining lung and resulted in severe pneumonia.
Despite these complications, in selected patients, endobronchial stents can reduce air leakage and prevent remaining lung from contamination with pleural fluid.
6. Prevention of bronchopleural fistula in pulmonary resection-bronchial stump coverage
To prevent postpneumonectomy bronchopleural fistula, coverage of the bronchial stump is recommended, especially for patients with high risk of BPF.
Pedicled intercostal and extrathoracic muscles, diaphragm, pericardium, pericardial fat pad, and pleura can be used to make a flap to coverage the bronchial stump [30, 31, 32]. There is no consensus for best bronchial stump coverage method and related techniques with several complications were defined in the literature. Diaphragm flaps can cause visceral herniation. The pedicled intercostal muscle flap is useful method for coverage of the bronchial stump but developing heterotopic ossification can cause severe problems. Omentum is a great tissue to promote re-vascularization and healing of the bronchial stump but it requires the opening of the abdominal cavity . Pericardial fat pad coverage appears to be safe and feasible when compared with other coverage techniques (Figures 9 and 10). It can be applied without risk of additional comorbidity and composes a mechanical barrier between bronchial stump and pleural cavity.
In modern thoracic surgery, bronchopleural fistula is still associated with significant morbidity and mortality. Treatment techniques have evolved and there are many options to use in patients with BPF, therefore surgeon must evaluate clinical status of the patient, the size, and location of the BPF and the status of the pleural cavity to select the treatment method that will show the most benefit.
It is important to remember that the best treatment is to prevent the disease. Therefore, rigorous surgical technique and bronchial stump coverage are the main steps in the treatment.
Conflict of interest
The authors declare no conflict of interest.
Appendices and nomenclature
|VATS||video-assisted thoracoscopic surgery|
Okuda M, Go T, Yokomise H. Risk factor of bronchopleural fistula after general thoracic surgery: Review article. General Thoracic and Cardiovascular Surgery. Dec 2017; 65(12):679-685. DOI: 10.1007/s11748-017-0846-1. [Epub 2017 Oct 12]
Deschamps C, Bernard A, Nichols FC 3rd, et al. Empyema and bronchopleural fistula after pneumonectomy: Factors affecting incidence. The Annals of Thoracic Surgery. 2001; 72:243-247 [discussion: 248]
Pforr A, Pages PB, Baste JM, et al. A predictive score for bronchopleural fistula established using the French database EPITHOR. The Annals of Thoracic Surgery. 2016; 101:287-293
Wright CD, Wain JC, Mathisen DJ, et al. Postpneumonectomy bronchopleural fistula after sutured bronchial closure: Incidence, risk factors, and management. The Journal of Thoracic and Cardiovascular Surgery. 1996; 112:1367-1371
Asamura H, Naruke T, Tsuchiya R, et al. Bronchopleural fistulas associated with lung cancer operations. Univariate and multivariate analysis of risk factors, management, and outcome. The Journal of Thoracic and Cardiovascular Surgery. 1992; 104:1456-1464
Martin J, Ginsberg RJ, Abolhoda A, et al. Morbidity and mortality after neoadjuvant therapy for lung cancer: The risks of right pneumonectomy. The Annals of Thoracic Surgery. 2001; 72:1149-1154
Wescott JL, Volpe JP. Peripheral bronchopleural fistula: CT evaluation in 20 patients with pneumonia, emphyema, or postoperative air leak. Radiology. 1995; 196:175-181
Seo H, Kim TJ, Jin KN, Lee KW. Multi-detector row computed tomography evaluation of bronchopleural fistula: Correlation with clinical, bronchoscopic, and surgical findings. Journal of Computer Assisted Tomography. 2010; 34:13-18
Gaur P, Dunne R, Colson Y, Gill R. Bronchopleural fistula and the role of contemporary imaging. The Journal of Thoracic and Cardiovascular Surgery. 2013; 148. DOI: 10.1016/j.jtcvs.2013.11.009
Nielsen KR, Blake LM, Mark JB, DeCampli W, McDougall IR. Localization of bronchopleural fistula using ventilation scintigraphy. Journal of Nuclear Medicine. 1994; 35:867-869
Raja S, Rice TW, Neumann DR, Saha GB, Khandekar S, MacIntyre WJ, et al. Scintigraphic detection of post-pneumonectomy bronchopleural fistulae. European Journal of Nuclear Medicine. 1999; 26:215-219
Boudaya MS, Smadhi H, Zribi H, et al. Conservative management of postoperative bronchopleural fistulas. The Journal of Thoracic and Cardiovascular Surgery. 2013; 146:575-579
Dutau H, Breen DP, Gomez C, et al. The integrated place of tracheobronchial stents in the multidisciplinary management of large post-pneumonectomy fistulas: Our experience using a novel customised conical self-expandable metallic stent. European Journal of Cardio-Thoracic Surgery. 2011; 39:185-189. DOI: 10.1016/j.ejcts.2010.05.020
Hollaus PH, Lax F, Wurnig PN, et al. Videothoracoscopic debridement of the postpneumonectomy space in empyema. The European Journal of Cardio-Thoracic Surgery. 1999; 16:283-286
Gossot D, Stern JB, Galetta D, et al. Thoracoscopic management of postpneumonectomy empyema. The Annals of Thoracic Surgery. 2004; 78:273-276
Robinson S. The treatment of chronic non-tuberculous empyema. Surgery, Gynecology & Obstetrics. 1916; 64
Eloesser L. An operation for tuberculous empyema. Surgery, Gynecology & Obstetrics. 1935; 60:1096-1097
Clagett OT, Geraci JE. A procedure for the management of postpneumonectomy empyema. The Journal of Thoracic and Cardiovascular Surgery. 1963; 45:141-145
Pairolero PC, Arnold PG, Trastek VF, et al. Postpneumonectomy empyema. The role of intrathoracic muscle transposition. The Journal of Thoracic and Cardiovascular Surgery. 1990; 99:958-966 [discussion: 966-8]
Deschamps C, Allen MS, Miller DL, et al. Management of postpneumonectomy empyema and bronchopleural fistula. Seminars in Thoracic and Cardiovascular Surgery. 2001; 13:13-19
Abruzzini P. Trattamento chirurgico delle fistole del bronco principale consecutive a pneumonectomia per tubercolosi. Chirur Torac. 1961; 14:165-171
Padhi RK, Lynn RB. The management of bronchopleural fistulas. The Journal of Thoracic and Cardiovascular Surgery. 1960; 39:385-393
Goldstraw P. Treatment of postpneumonectomy empyema: The case for fenestration. Thorax. 1979; 34:740-745
Estlander JA. Sur le resection des cotes dans l’empyeme chronique. The Medico-Chirurgical Review. 1891; 8:885-888
Lois M, Noppen M. Bronchopleural fistulas: An overview of the problem with special focus on endoscopic management. Chest. 2005; 128:3955-3965
Jones NC, Kirk AJ, Edwards RD. Bronchopleural fistula treated with a covered wallstent. The Annals of Thoracic Surgery. 2006; 81:364. DOI: 10.1016/j.athoracsur.2004.09.054
Klotz LV, Gesierich W, Schott-Hildebrand S, et al. Endobronchial closure of bronchopleural fistula using Amplatzer device. Journal of Thoracic Disease. 2015; 7:1478-1482
Hamid UI, Jones JM. Closure of a bronchopleural fistula using glue. Interactive Cardiovascular and Thoracic Surgery. 2011; 13:117-118. DOI: 10.1510/icvts.2011.270397
Amaral B, Feijó S. Fistula of the stump: A novel approach with a “stapled” stent. Journal of Bronchology and Interventional Pulmonology. 2015; 22:365-366. DOI: 10.1097/LBR.0000000000000172
Klepetko W, Taghavi S, Pereszlenyi A, et al. Impact of different coverage techniques on incidence of postpneumonectomy stump fistula. European Journal of Cardio-Thoracic Surgery. 1999; 15:758-763
Anderson TM, Miller JI Jr. Use of pleura, azygos vein, pericardium, and muscle flaps in tracheobronchial surgery. The Annals of Thoracic Surgery. 1995; 60:729-733
Anderson TM, Miller JI Jr. Surgical technique and application of pericardial fat pad and pericardiophrenic grafts. The Annals of Thoracic Surgery. 1995; 59:1590-1591
Okumura Y, Takeda S, Asada H, et al. Surgical results for chronic empyema using omental pedicled flap: Long-term follow-up study. The Annals of Thoracic Surgery. 2005; 79:1857-1861. DOI: 10.1016/j.athoracsur.2005.01.001