82: Bronchopleural Fistula After Pneumonectomy

Bronchopleural fistula (BPF) occurs in 1.5% to 7% of patients after pneumonectomy. BPFs can have devastating consequences, with mortality of 25% to 71% and prolonged hospital stays involving multiple procedures for survivors.^1,2 Presentation may be acute or delayed: The majority of patients present within 3 months postoperatively, most of whom do so within the first 12 days after surgery.^2,3 Late-onset BPF can be more difficult to diagnose and generally is seen in the setting of empyema. The basic principles of successful BPF management include protection of the remaining lung, control of sepsis, debridement of necrotic tissue, closure of the fistula reinforced with vascularized tissue, and obliteration of the pleural space.

Risk factors for the development of BPF after pneumonectomy include anatomic, technical, and patient factors (Table 82-1).^4,5 Right pneumonectomy is associated with a fourfold to fivefold higher incidence of BPF than left pneumonectomy, likely related to anatomic differences between the right and left mainstem bronchi.⁶ A right pneumonectomy stump has minimal mediastinal coverage of the bronchial stump compared with a left-sided stump, which retracts underneath the aorta into the mediastinum when properly fashioned (Fig. 82-1). The right mainstem bronchus is also oriented much more vertically than the left, which permits secretions to pool in the bronchial stump. Finally, the vascular supply to the left mainstem bronchus is augmented by direct vascular branches as the bronchus passes behind the aorta. The blood supply on the right travels from the trachea via local branches in the subcarinal space, which are often disrupted by dissection and lymph node removal.

Technical factors related to BPF formation include devascularization of the bronchial stump by excessive dissection; a long bronchial stump with increased pooling of secretions and risk of secondary infection that leads to stump breakdown; stump closure with suture instead of staples; and closure under tension, as in the case of a thickened bronchial wall at the point of closure.^4,7 Closure under tension also can be implicated in a predominance of right-sided BPFs because the diameter of the right mainstem bronchus at the point of transection generally is larger than the left. Although excessive bronchial dissection increases the risk of BPF, mediastinal lymphadenectomy has not been shown to increase the risk of BPF.⁸

The primary patient factor associated with BPF is postoperative mechanical ventilation. The overall BPF incidence in a series of 256 patients was 3.1%, which increased to 19.3% in patients requiring postoperative ventilation.⁹ Prolonged high airway pressures likely create trauma at the level of the stump that impairs healing. The need for postoperative mechanical ventilation also may explain the association between BPF and severe chronic obstructive pulmonary disease, as well as low forced expiratory volume in 1 second (FEV₁) and the diffusion capacity of the lung to carbon monoxide (D_LCO). Other patient factors include those that impair wound healing, such as preoperative radiation therapy (>45 Gy), poor nutritional status, and prolonged corticosteroid use. Local infectious processes such as tuberculosis or the presence of empyema also increase the risk of BPF.

Coverage of the bronchial stump may reduce the incidence in patients at an increased risk for developing BPF after pneumonectomy.⁴ Bronchial stump coverage with an intercostal muscle flap was associated with a reduction in the incidence of BPF from 8.8% to 0% in a randomized trial involving diabetic patients.¹⁰ Coverage is likely especially important on the right side, where the stump is exposed in the pneumonectomy space. Many groups routinely cover all right-sided stumps, covering left-sided stumps only for patients with increased risk. Coverage can be provided by using a variety of local and distant tissues as vascularized flaps that are tacked over the bronchial stump. Tissues used routinely include pericardial fat pad and intercostal muscle flaps. If these tissues are inadequate, or if the patient is thought to be at extraordinary risk of stump complications, larger muscle or omental flaps are used.

BPF should be suspected in patients who develop fever, empyema, aspiration pneumonia, an excessively productive cough, or an increasing air leak or amount of pleural air after lung resection. Many patients present early with a fulminant course, including expectoration of large amounts of serous or seropurulent fluid, respiratory distress, and sepsis. Appearance of these symptoms should raise the index of suspicion and be followed by a quick and accurate diagnosis before there is overwhelming aspiration of pleural fluid into the remaining lung. This presentation is most common in large fistulas with abundant drainage of pleural fluid into the tracheobronchial tree. Small fistulas more commonly present with productive cough with serous or purulent sputum, fever, hemoptysis, or subcutaneous emphysema. Findings on chest radiograph suggestive of BPF include progressive subcutaneous or mediastinal emphysema, development of a new air–fluid level in a previously opacified pneumonectomy space, a 2-cm drop in an existing air–fluid level with shift of the mediastinum away from the pneumonectomy space, or new development of multiple air–fluid levels. Late-onset BPF often presents with nonspecific symptoms, including low-grade fever, anorexia, fatigue, and weight loss similar to late postpneumonectomy empyema. Proving the presence of a fistula in these patients can be more problematic because the connection is often small and not identified by bronchoscopy. Nuclear medicine techniques have been used to confirm the presence of radiolabeled inhaled gas in the postpneumonectomy space.

Whether the diagnosis is apparent clinically or radiographically or suggested by advanced testing, all patients should undergo diagnostic bronchoscopy. A large fistula generally can be visualized. Fistulas smaller than 1 to 2 mm may be difficult to identify. Perhaps more important, bronchoscopy provides information about the length of the remaining bronchial stump and the condition of the tissue at the level of the stump that can be helpful in planning definitive repair. In addition, pulmonary toilet can be optimized by aspirating any fluid or secretions in the remaining lung.

Draining the Pleural Space

Acute management focuses on controlling life-threatening conditions, including postural drainage with the affected lung positioned down in cases of airway flooding, early thorough pleural drainage to prevent sepsis and aspiration pneumonia, and appropriate antibiotic therapy. Adequate nutrition is also paramount to a favorable outcome.

Drainage can be performed at the bedside with a tube thoracostomy under local anesthesia placed to either balanced drainage system or water seal but not suction. Immediate drainage is especially important for patients who present with large fistulas in which a significant volume of pleural contents is draining into the airways, potentially flooding the contralateral lung. Care must be taken to place the tube above the level of the previous thoracotomy incision because the diaphragm will be elevated as part of the normal thoracic remodeling that occurs after pneumonectomy. In addition, the patient should be in the supine position when the thoracostomy tube is placed. Lateral positioning places the remaining lung in a dependent position and encourages further aspiration. Once the tube is in place, further positional maneuvers to prevent aspiration include maintaining the patient in as close to an upright position as possible and rotating the patient such that the pneumonectomy side is down.

Once the urgent situation is controlled and the patient is started on appropriate parenteral antibiotics, the remaining pleural debris and necrotic tissue are removed. Debridement can be accomplished by means of an open thoracic window or thoracotomy. The selection of technique depends on the patient's overall condition. At this stage, debilitated or critically ill patients may tolerate a major thoracic procedure poorly, especially a prolonged procedure involving muscle flaps or other approaches used to definitively address the fistula. These patients often benefit from a period of treatment with a simple open window thoracostomy to permit control of sepsis and nutritional support followed by delayed definitive closure.

Technique for Open Window Thoracostomy

Open window thoracostomy allows open drainage of an infected intrathoracic space by using a U-shaped incision over the most dependent portion of the space (Fig. 82-2). Segments of one or two ribs are removed to limit the tendency of the opening to contract and close. The skin flap then is sutured directly to the parietal pleura with interrupted absorbable sutures to create an epithelialized tract, which both maintains the patency of the window and encourages healing. The window should not be placed too far posteriorly such that it is difficult for the patient to manage. Similar care is taken to avoid placing the window too far inferiorly, where it might interfere with the diaphragm. Other techniques, including placement of large-bore drainage tubes through the window as stents, also will help to maintain patency. Dressing changes with moistened gauze then are performed until the cavity is sterilized. Very small fistulas may close spontaneously once the local sepsis is eradicated. Most, however, require definitive closure. Patients in generally good condition at the time of presentation can proceed directly to simultaneous debridement of the pleural space and definitive closure.

Closing the Bronchopleural Fistula

Most patients can tolerate early exploration and closure of the fistula, and this procedure should be undertaken as soon as the patient is medically stable. Exploration is preferentially performed by means of a posterolateral thoracotomy on the ipsilateral side, with lung isolation via selective intubation of the contralateral mainstem bronchus to prevent further soilage of the remaining lung. If not readily visible, the fistula can be identified with the aid of positive-pressure ventilation while covering the area of the bronchial stump with irrigation. The pleural space is thoroughly irrigated and debrided to remove all necrotic tissue. The bronchial stump is carefully dissected to minimize trauma to its blood supply. All attempts are made to leave a final stump that is less than 1 cm in length measured from the carina (Fig. 82-3). If sufficient length remains on initial exploration, stapling device can be used to reclose the stump. In most cases, there is too much inflammation to permit stapling, however, and the mobilized bronchial stump is reclosed with interrupted monofilament sutures. A balance must be obtained between exposing enough bronchus to avoid tension on the closure and avoiding too much exposure, which could damage the blood supply.

Reinforcing the suture line with vascularized tissue is perhaps the most important aspect of closure. Pedicled flaps of the muscle or omentum are mobilized into the chest and sutured over the bronchial stump.^3,11 Flap choice depends on the quality of the tissue, damage to potential flap muscles from the previous thoracotomy, and the amount of space to be filled. The serratus anterior is used commonly after pneumonectomy. This muscle is often preserved during the initial operation even when an open procedure was done, because of its utility in dealing with potential complications. The flap is based on the vascular pedicle that runs on the lateral undersurface of the scapula. The muscle is mobilized and inserted between the ribs in either the second or third interspace, where it will generally reach the hilum with no tension. If the interspaces are tight and can possibly compromise the vascular supply of the flap, a segment of the third rib can be removed to allow the flap to comfortably enter the pleural space. The flap generally is secured with interrupted absorbable sutures to the peribronchial or mediastinal areolar tissue. This tissue aids in healing and infection control because its blood supply emanates from regions beyond the inflamed field. In cases where the stump is frankly necrotic or densely scarred into the mediastinum, the fistula may not be able to be closed directly. In this event, a muscle or omental flap is sutured to the freshened edges of the open fistula or surrounding mediastinum to occlude the communication and permit healing. An advantage of using a relatively large muscle such as the serratus anterior to close the fistula is that it also contributes bulk to fill some of the dead space in the postpneumonectomy chest.

In severely ill patients with difficult bronchial stumps, simultaneously placing a temporary tracheostomy with a long cuffed tube in the contralateral mainstem bronchus may be useful. The tracheostomy is left in place for several weeks to permit the flap to become fixed over the opening of the fistula without the stress of positive-pressure ventilation, which can slow healing.

Case reports and small case series have also reported successful BPF treatment using endoscopic techniques. The use of bronchoscopic placement of stents, glues, sealants, coils, submucosal tissue expander injection, and devices designed for transcatheter closure of cardiac defects have all been reported to successfully lead to closure of BPFs after pneumonectomy.³ However, these techniques should likely be considered only when primary repair fails or is not possible because of patient condition. Generally, these only work with smaller BPFs.

Once the fistula is closed, the pleural space must be sterilized. In early-onset BPF, when there has been minimal contamination, thorough operative debridement and irrigation may be sufficient. In more advanced cases with greater contamination, sterilization can be accomplished by creating an open window with dressing changes as described earlier or by closure over irrigation catheters after the fistula has been repaired. Chest tubes or other irrigation catheters can be placed and irrigated either continuously or several times daily with antibiotic solution. When there is no remaining evidence of infection within the space, on the basis of either Gram stain of granulation tissue or culture of irrigation fluid, definitive closure is performed.

More recently, several retrospective studies have reported successful management of empyema cavities using vacuum-assisted closure (VAC) devices, even in the setting of a BPF. Although limited, these studies suggest that VAC, as an adjunct to the standard treatment, can potentially alleviate the morbidity and reduce inpatient length of treatment in patients with empyema after lung resection.¹² Management typically involves filling the intrathoracic cavity with foam to the superficial wound edges. Negative pressure, gradually increased from –25 to –125 mm Hg over time, is applied to clean the wound and support healing. The VAC is generally changed every 2 to 3 days.

Occasionally, it is impossible to access the bronchial stump for effective repair, especially on the left side when the stump is retracted underneath the aorta (Fig. 82-4). In such cases, fistula closure can be approached via median sternotomy.¹³ This approach permits exposure of the carina in a previously nonoperated field between the superior vena cava and the aorta, and the mainstem bronchus can be redivided and closed in a field free of infection. After median sternotomy, the pericardium is opened, and dissection between the superior vena cava and aorta exposes the carina. If possible, a segment of the mainstem bronchus should be resected to provide a fresh edge for stapling or suture closure and to avoid contamination from the distal bronchial remnant. Another approach to the carina is through the right chest for a left-sided fistula. A right posterolateral thoracotomy is performed in this approach, and the lung is mobilized and retracted anteriorly so the mediastinal pleura can be incised at the level of the subcarinal area. The left bronchial stump can be mobilized, restapled flush with the carina, and covered with a flap of intercostal muscle, pericardial fat, or mediastinal tissue.¹⁴ Central extracorporeal membrane oxygenation (ECMO) can be utilized if necessary if the patient has instability during the attempted repair.

Obliterating the Remaining Pleural Cavity

The final step in the treatment of BPF is obliteration of the remaining pleural space. The patient's overall condition and suitability for complete closure must be carefully reevaluated before taking this final step. Most closure failures are related to persistent or recurrent BPF. Patients with a chronic fistula, carcinomatosis within the space, persistent infection within the space, or poor nutritional status should not undergo obliteration maneuvers unless or until these issues have been addressed. A period of treatment with open thoracic window and adequate nutritional support can improve the patient's likelihood of a positive long-term outcome.

Obliteration of the pleural space can be accomplished by one or a combination of three techniques. The first option is to fill the sterilized cavity with antibiotic solution (Clagett maneuver). If the chest was closed initially over irrigation catheters, obliteration is a simple procedure. Antibiotic solution is infused into the cavity until it is completely filled, the irrigation catheters are removed, and the site is suture closed. If the patient was treated initially with an open thoracic window, the skin edges are excised and flaps are mobilized to permit closure without tension. The chest is filled with antibiotic solution in a similar fashion, and the window then is closed in multiple layers to prevent leakage of fluid. Antibiotic selection is tailored to culture and sensitivity tests rather than to a set of standard antibiotics. Excessive doses of intrapleural antibiotics can result in renal failure or other systemic complications and should be avoided. This technique was described originally by Clagett and Geraci¹⁵ in 1963 as a two-stage procedure in which open-window drainage was followed by obliteration of the space with antibiotic fluid without direct fistula closure. The technique is used rarely in its original form today, however, because of recurrences related to persistence of the fistula. The more common approach is the modified version with an intermediate step of fistula closure with muscle flap as described earlier.

The second technique involves transposition of muscle flaps that fill the pleural space with vascularized tissue (Fig. 82-5). Muscle flaps are an excellent choice because of their rich blood supply and ability to extend to almost any region of the pleural space. The choice of flaps depends on the availability and suitability of local muscles. Latissimus dorsi is often the largest muscle available in this location but frequently has been transected at the time of the original thoracotomy. Previously transected latissimus dorsi is unlikely to survive as a transposed flap. Many groups intentionally preserve the serratus anterior at initial operation for later use as a flap (Fig. 82-6). The serratus anterior is mobilized with maintenance of its attachments to the upper scapula and passed into the chest between the ribs or through a window created by resecting a segment of the second or third rib. Other useful local muscles include pectoralis major for the anterior portion, trapezius for the apical portion, and rectus abdominis for the caudal portion of the space. The number of muscles required relates to both the size of the remaining cavity and the quality and bulk of the muscles. Many patients with BPF have diminished muscle bulk from chronic debilitation and may not have sufficient muscle tissue to fill the space. In such cases, the highly vascularized omentum is an excellent replacement for or addition to local muscle flaps and can be mobilized from the abdomen through a substernal tunnel (Fig. 82-7).

The third technique is thoracoplasty, in which multiple ribs are resected to allow chest wall soft tissue to collapse inward and fill the pneumonectomy space. Thoracoplasty was described originally by Alexander¹⁶ in 1937 for the therapy of tuberculosis and involved resection of 10 or 11 ribs. This procedure was highly morbid and disfiguring, and had a profoundly negative impact on the physiologic function of the remaining lung. Most postpneumonectomy spaces can be completely filled by removing ribs two to eight; however, this is still significantly disfiguring, may limit arm and shoulder function, causes chest wall paresthesias, and requires prolonged convalescence. In the current era, thoracoplasty has a limited role in combination with muscle flap transposition (Fig. 82-8). Available muscle flaps are transposed to fill as much space as possible. Then, simultaneously or in a separate procedure, a limited thoracoplasty (often involving only two to three ribs) is performed to obliterate any remaining space.

Outcomes after BPF are related most strongly to the underlying disease and condition of the patient at the time of presentation. The reported overall mortality for this complication remains distressingly high. The main cause of death in these patients is aspiration pneumonia of the contralateral side, and a large number never stabilize enough to permit repair of the fistula. Aspiration pneumonia occurs more commonly when the fistula occurs shortly after surgery. A second group of patients survives the initial insult long enough to receive a drainage procedure, such as open window thoracostomy, but never progresses to closure. Regnard et al. described the treatment of 30 postpneumonectomy patients with initial open window thoracostomy. Of those, seven (23%) received open window thoracostomy with dressing changes as their only definitive treatment. Full repair was not accomplished in this group because of patient death, other major illnesses, locally recurrent or metastatic cancer, or patient choice.¹⁷

The modified Clagett technique is the simplest method of definitive treatment and limits the operative morbidity associated with flap harvest; however, the outcomes reported have been suboptimal. Pairolero et al. reported their results with a three-step modified Clagett procedure including muscle flap reinforcement of the bronchial stump in 45 patients. They reported an ultimately successful outcome in 26 patients (58%), with an average of 5 surgical procedures per patient over 34 hospitalization days and 6 operative deaths.¹⁸ If the Clagett technique fails, the open window thoracostomy is recreated, and a more complex method of closure such as with muscle flap is attempted.

Better results have been noted after muscle flap transposition. Miller et al.¹⁹ reported five patients successfully treated with multiple muscle flaps, where an average of two muscles per patient and limited thoracoplasty were used. Regnard et al.¹⁷ successfully treated 17 of 23 pneumonectomy patients with open window thoracostomy followed by flap transposition. Of the six initial failures, three underwent successful reoperation with additional muscle or omental flaps for an overall success rate of 87%. The remaining three patients were not considered to be suitable for further attempts and were converted back to definitive therapy with open window drainage. Michaels et al.²⁰ used a combination of open window thoracostomy, repair of the fistula with muscle flap reinforcement, additional intrathoracic muscle transposition, and limited thoracoplasty to treat 16 patients. Four (25%) had initial failure with recurrence of empyema but eventually were treated successfully after additional procedures. Of the 15 patients who survived the perioperative period, five died of their lung cancer, two were alive with metastatic disease, and eight had no evidence of recurrent cancer at a median follow-up of 19 months. These data highlight the importance of minimizing the number of operative interventions and maximizing the quality of life in this patient population with limited life expectancy as a consequence of their underlying disease.

BPF continues to be a frustrating complication of pneumonectomy that leads to significant morbidity and mortality even in the modern era. Progress in the care of critically ill patients has given formerly inoperative patients the chance for curative resection. With recent improvements in induction therapy for lung cancer, more postinduction patients may become candidates for resection. The rising incidence of multidrug-resistant tuberculosis is also creating a resurgence of surgical intervention for tuberculosis, which carries a high risk of postresectional BPF. These shifts in the patient population may lead to a rising incidence of BPF in the future. As is often the case, the large number of approaches to this problem reported in the literature is reflective of the complexity of the problem and lack of a successful, easily applied solution. A comprehensive plan must be established when caring for these patients, including nutritional support, control of sepsis, closure of the fistula, and obliteration of any remaining space.

Although BPF in general remains a rare event, attention to the management as well as prevention of this dreaded complication is important for the lung cancer surgeon. The known risk factors for patient disability and the technical factors that put these patients at risk are well known and should be avoided. Great care at the initial surgery remains the best way to minimize the risk of BPF.

Regarding the choice of muscle flap, my personal preference is the serratus anterior, because of its bulk, which can help to fill the pneumonectomy space. However, we often use multiple muscle flaps for larger spaces.