Diagnostic Puzzlers: Shortness of breath after pneumonectomy and chemotherapy

A 67-year-old woman underwent right pneumonectomy for non-small-cell carcinoma of the right lung. Her postoperative course was uneventful, and she was discharged from the hospital on the fifth day.

Subsequently, she underwent chemotherapy. Six weeks later, she was admitted with a complaint of shortness of breath. She denied fever, chills, rigors, and excess sputum production.

The patient was in obvious distress, with a respiration rate of 22 breaths per minute and the use of accessory muscles. She was afebrile. Her heart rate was 102 beats per minute and her blood pressure was 110/82 mm Hg. No clubbing or cyanosis was noted.

Heart sounds were normal. Air entry was decreased in the fields of the left lung, with slight unilateral wheezing. The abdominal and neurologic examinations were unremarkable.

The patient's white blood cell count was 10,000/µL, with 73% neutrophils, 22% lymphocytes, and 5% monocytes. Her hemoglobin level was 14.1 g/dL, and hematocrit was 36%. Other laboratory parameters were within normal ranges, with the exception of an elevated alkaline phosphatase level of 240 IU/L (normal level, 20 to 140 IU/L). The arterial blood gas levels on room air were pH, 7.42; PCO₂, 31 mm Hg; and PO₂, 62 mm Hg.

A chest radiograph was obtained (Figure 1).

What is the likely diagnosis? How would you proceed?

Discussion

In the normal postpneumonectomy chest, residual largespaces in the pleural cavity are filled in one of the followingways: entry of fluid, increased expansion of the remaininglung, or a shift of the mediastinum/diaphragm towardthe newly created space. When fluid enters the cavity,it increases until the pneumothorax is obliterated.

When fluid in the cavity decreases and is replaced byair, as in our patient, a BPF from the stump is indicated.Thus, the characteristic radiologic signs of postpneumonectomyBPF include failure of the potential pleuralspace to fill with liquid, inspiratory shifting of the mediastinum to the contralateral(nonoperated) side, and an abrupt decrease in the gas-liquid level of more than 2 cm(0.8 in).

A BPF is a sinus tract between the bronchus and the pleural space that results froma necrotizing infection or trauma. The most common traumatic cause is failure to obtaingood bronchial closure and healing after partial or complete resection of the lung(Table). Failure to heal may result from improper initial closure, inadequate bloodsupply, infection at the bronchial stump, or a residual malignant tumor at thebronchial stump.

BPF typically presents 7 to 15 days following resection, although delayed BPFshave been reported.¹With delayed BPF, a new air-fluid level appears in a previouslyopacified hemithorax.

Cough and changes in the air-fluid pattern on the chest radiograph are criticalwarning signs of BPF. Other manifestations include fever with serosanguineous orpurulent sputum.Acute respiratorydistress may occur ifa large BPF resultsin aspiration to thecontralateral lung orif a tension pneumothoraxdevelops.

BPF can lead toempyema formation.In our patient, therewas no evidence ofinfection at thebronchial stump orin the pleural spaceand there was no evidence of recurrent cancer at the bronchial stump.

The incidence of BPF is about 4.5% to 20% afterpneumonectomy and 0.5% after lobectomy.^2,3 BPFcan cause significant morbidity, prolonged hospitalization,and mortality. A multivariate analysis ofthe risk of BPF in patients undergoing resectionsfor lung cancer identified right-sided resection,pneumonectomy (especially right pneumonectomy),mediastinal lymph node resection, highdosepreoperative radiation therapy, and residualor recurrent carcinoma at the bronchial stump aspredisposing factors.⁴ Nonoperative risk factors includeddiabetes mellitus, hypoalbuminemia, cirrhosis,and administration of corticosteroids.

When BPF is not clearly visible on bronchoscopy, bronchography⁵ or ventilationscintigraphy^6,7 can be used to localize the site. Instillation of methylene blue into thebronchial tree, with its subsequent appearance in the chest drainage, can confirmBPF location. The site can also be determined by bronchoscopic guidance of a balloon-tipped catheter into selected airways and subsequent inflation of the balloon. Ifthe bronchus contributes to the BPF, balloon occlusion decreases or eliminates theair leak.

Capnography can also be used to identify the bronchial segment associated withthe BPF. End-tidal carbon dioxide is measured by connecting a capnograph to a polyethylenecatheter that is passed through the bronchoscopic channel and placed systematicallyinto different bronchi. The absence of a capnographic tracing in a particularsegment or subsegment suggests the presence of a BPF.

Postpneumonectomy BPF is a serious complication.⁸ Drainage of the pleural spacevia a chest tube is a critical first step for all patients, in order to limit endobronchialcontamination and prevent drowning. If conservative management with tubedrainage, antibiotics, and nutritional support fails to close the BPF, surgical interventionshould be considered. In general, suture reclosure of the bronchial stump withvascularized flap coverage alleviates acute BPF, which usually occurs less than 2weeks after surgery.⁹ Appropriate timing and correct application of available techniquesare of primary importance in obtaining optimal results.¹⁰

Postpneumonectomy patients who present with delayed BPF are unlikely to havedirect reclosure of the BPF. These patients may have closure of the BPF by an anteriortranspericardial approach or thoracotomy with muscle flap¹¹ to fill the pleuralspace, or muscle flap coverage of the BPF with a limited thoracoplasty to obliteratethe pleural space. However, these procedures are associated with high morbidity,mortality, and cost. Since many of these patients are poor candidates for a secondthoracic operation of this magnitude, they may be treated with endoscopically placedtissue adhesives to seal the BPF.

Various endoscopic options have been successful in about 60% to 100% of BPFcases, significantly reducing morbidity and mortality.^12-15 These include endoscopicplacement of a glutaraldehyde-sterilized lead shot,¹⁶ a balloon catheter (occlusion),¹⁷gel foam and tetracycline,¹⁸ an autologous blood patch,¹⁶ vascular embolizationcoils,¹⁹ N-butyl-2-cyanoacrylate,¹³ fibrin adhesive material, and a gelatin-resorcinolmixture plus cryoprecipitate fibrin glue to obliterate the BPF.,^{2,12-15,20,21}

Varoli and colleagues1 reported successful endoscopic treatment with multiplesubmucosal injections of polidocanol-hydroxypoliethoxidodecane on the margins ofthe BPF by using an endoscopic needle inserted through a flexible bronchoscope.Some have used adhesive glue to close post-traumatic peripheral BPF.²² Others have reported successful endobronchial closure with vascular occlusion coils and cyanoacrylateglue via flexible bronchoscopy²³ or angiography catheters passed throughtracheostomy tubes.²⁴ Baumann and associates²⁵ have studied the use of humanspongiosa and fibrin sealant in successful closures of BPF

These bronchoscopic procedures are more successful in closing small BPFs of lessthan 5 mm, as in our patient. The flexible bronchoscope is more advantageous thanthe rigid bronchoscope, because the former provides superior and precise access to agreater portion of the bronchial tree.¹⁵ Although video-assisted thoracoscopic placement²⁶and CT-guided percutaneous transthoracic application²⁷ of fibrin sealant havebeen used to seal pulmonary air leaks, they are invasive procedures.

Each sealant acts first as a plug that mechanically seals the leak and later as an inducerof an inflammatory process with mucosal proliferation and fibrosis that createsa permanent seal.⁵ It has also been shown that repair of a BPF occurs by organizationof granulation tissue caused by foreign bodies.²⁸ Epithelialization with typical respiratoryepithelium has been reported.²⁹ While there are no large controlled trials todocument the efficacy of endobronchial procedures that use various tissue adhesivesto close the fistula, multiple case reports and series suggest their effectiveness in selectedpatients.

As an alternative, the Nd:YAG laser has been used to close small BPFs, but thistechnique has not been widely reported.³⁰ Other methods include placement of astent in the bronchial stump to prevent air leaks and to close the BPF^31,32 and use ofintrabronchial valves.

Bronchoscopic closure eliminates the risk of general anesthesia and major reconstructivesurgery. The BPF can be closed endoscopically when there is no evidence ofinfection in the pleural cavity. Persons without infection do not require prior drainageof the pleural cavity. If the patient has empyema, insertion of a chest tube to drain theinfected pleural space is advisable before endoscopic closure is attempted.¹³ Bronchoscopicclosure can be used in patients on mechanical ventilation or in debilitated personswho are at high risk with use of general anesthesia.

Outcome in this case

Closure of the BPF was performed by injecting 2-component fibrin-cryoprecipitateglue through a catheter inserted via the operative channel of a bronchoscope. Calciumgluconate, cryoprecipitate, and topical thrombin (1000 IU/mL) created a fibrinclot that occluded the BPF. A total of 1 mL of each of these solutions was injected.Cryoprecipitate was obtained from the blood bank, and thrombin was obtained fromthe pharmacy.

The fibrin sealant that we used is a dual-component biologic adhesive. Its actionmimics the final stage of clotting, whereby fibrinogen (in the form of cryoprecipitate)--in the presence of factor XIII, thrombin, and calcium--polymerizes to form afibrin clot, which is gradually adsorbed by fibrinolysis.³³ It is important to note thatthe 2 fibrin components should be applied directly to the BPF site and allowed tomix, because clot formation begins within seconds.

The patient's dyspnea improved markedly, and the air leak in the chest tubestopped, indicating occlusion of the BPF. Over the next few days, the right side of thepleural cavity filled with fluid, further indicating closure of the BPF. The chest tubewas removed 5 days after the procedure, and the patient was discharged. The BPFhad completely healed by 2 weeks after the procedure.

References:

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