Clinical Scenario

A 55-year-old white male with a 20–pack-year history of smoking presented with syncope, a 2 month history of increasing exertional dyspnea, and a cough that had been refractory to bronchodilators and antibiotics. He was married and lived with his wife. The patient’s father and one brother had died of lung cancer. The emergency department physician believed that the patient was disabled, required special care and assistance, and warranted immediate hospitalization. The physical examination, however, was normal except for stridor heard over the trachea during forced expiration. The workup for syncope included an electrocardiogram, two-dimensional echocardiogram, bilateral carotid duplex ultrasonography, and computed tomography (CT) of the head, all of which were normal. A pulmonary consultant ordered a CT scan of the chest, which revealed a 1.5 cm right upper lung (RUL) nodule and a 4 cm right paratracheal mass invading the trachea (Figure 1).

Figure 1 A, Normal tracheal lumen proximal to the tumor. B, Right paratracheal mass compressing and invading the lower trachea below the aortic arch. C, The normal tracheal lumen is seen at the level of the main carina distal to the tumor. D, Right upper lobe spiculated pulmonary nodule.

Question 1: If this patient is proven to have primary lung malignancy, which of the following is the most accurate predictor of survival?

Answer: D

Estimated survival is an important factor for decision making in all disease processes. If this patient has primary lung cancer, he would be clinically staged IIIB because of tracheal involvement (T4 tumor). In such cases of advanced cancer, prognostic considerations are especially important because treatment goals nearing the end of life may change from efforts to prolong life at all costs, to those of palliating symptoms, preserving quality of life, and maintaining dignity. Estimating survival based on objective data is warranted because physicians’ subjective assessments of predicted survival are often incorrect, with the direction of error being usually optimistic.*¹ Patients, in most circumstances, want their doctors to be realistic when it comes to prognosis. Although exact numbers may not be requested by patients or their families, having knowledge of relatively accurate prognostic indicators helps physicians conduct meaningful and honest discussions.

A clinical symptom such as stridor, although a sign of severe laryngeal or tracheal obstruction,² does not delineate a benign or malignant disease process. In general, stridor and other symptoms of upper or central airway obstruction (CAO), including exertional dyspnea, wheezing, or even syncope, are nonspecific.³ In fact, results from analysis of 100 variables from several studies showed that only dyspnea, dysphagia, weight loss, xerostomia, anorexia, and cognitive impairment were strongly and independently associated with cancer patient survival. These signs and symptoms were outranked, however, by assessment of performance status,¹ which deservedly has become a “sixth vital sign” in clinical oncology.^† Because performance status is the strongest prognostic indicator of survival in patients with cancer, it is frequently used as an entry criterion and adjustment factor in clinical trials of anticancer treatment.¹ One commonly used measure of performance is the Karnofsky Performance Status score (range, 0 to 100 in 10 point increments, where 0 is death and 100 is perfect health), a general measure of functional impairment in which the lower the score, the worse is survival for most serious illnesses.¹

This patient was assigned a Karnofsky score of only 40. In the setting of lung cancer, known central airway obstruction, and Karnofsky scores below 50, a combination of interventional bronchoscopy and external beam radiation therapy (EBRT) to relieve the airway obstruction has been shown to be the therapeutic option of choice, often resulting in rapid restoration of airway patency, improved symptoms, improved performance status, and increased survival.⁴

The case continues

Several hours after admission, the patient lost consciousness while standing to go to the restroom. He was promptly intubated with a 7.5 mm endotracheal tube (ETT) and was placed on mechanical ventilation assist control–volume control mode (ACVC): tidal volume was 500 mL, respiratory rate 14/min, fraction of inspired oxygen (FiO₂) 1.0 and flow 80 L/min, and positive end-expiratory pressure (PEEP) 5 cm H₂O. On these settings, the peak airway pressure was 60 cm H₂O and plateau pressure was 20 cm H₂O. Flexible bronchoscopy was planned to determine the pattern of tracheal obstruction, to identify associated mucosal changes, and to potentially support the indication for a therapeutic airway procedure. The only flexible bronchoscope available had an outside diameter of 6 mm.

Question 2: The next appropriate step is to:

Answer: D

In the absence of evidence that the endotracheal tube is kinked, or that the patient’s high peak airway pressures are due to mucus plugging or bronchospasm, it is likely that the obstructing tracheal mass itself is responsible for elevated peak airway and normal plateau pressures. Bronchodilators, therefore, would not be expected to improve respiratory status. Bronchoscopy should be rapidly performed, given that ventilation may be difficult because of a less than 2 mm difference between the size of the outer diameter of the bronchoscope and the internal lumen of the endotracheal tube.

Ideally, a No. 8 or larger ETT is preferred for bronchoscopy because it allows proper ventilation during the procedure and potentially prevents a further increase in peak airway pressure or development of auto-PEEP. These tubes provide at least a 2 mm difference between the scope and the ETT diameter, preventing critical alterations in ventilatory parameters.⁵ Changing the ETT, however, by extubation and repeat laryngoscopy or by use of a tube exchanger is hazardous in a patient with critical tracheal obstruction. Reintubation may be difficult, and should the airway be lost, ventilation cannot be ensured. A safer approach may be to perform inspection flexible bronchoscopy through the existing ETT while monitoring peak airway pressures, tidal volumes, heart rate, and oxygenation. In case of tachycardia, a rise in blood pressure, or oxygen desaturation during the procedure, the bronchoscope can be immediately withdrawn until stable vital signs return.

The case continues

Flexible bronchoscopy was performed after a bite block was inserted into the mouth and was secured around the existing ETT. A swivel adapter with a fitted rubber cap was attached, allowing bronchoscopy with minimal loss of tidal volume. The FiO₂ was increased to 1.0, starting 5 minutes before the procedure, and continued until after the procedure, then was titrated down to prebronchoscopy levels. PEEP was removed during bronchoscopy to avoid raising peak airway pressures by as much as 25 mm Hg.⁶ If discontinuation of PEEP had not been feasible, it would have been reduced by 50%. Volume control ventilatory mode was preferred so that the increasing airway resistance secondary to the bronchoscopy would not result in reduced tidal volume. If pressure-controlled ventilation had been used, the peak pressure setting would have been increased to compensate for the loss of tidal volume consequent to the increased resistance. Moderate sedation was achieved with 2 mg intravenous midazolam. Had the patient been unable to cooperate or otherwise tolerate the procedure comfortably, supplemental doses may have been needed in 1- to 2-minute increments and according to moderate sedation guidelines used in our institution. To remove airway secretions, bronchoscopic suction was applied using short, 3 second or less bursts, because as much as 200 to 300 cm³ of the patient’s tidal volume can be removed during each suction period.⁶

A mass was seen protruding from the right lateral and posterior walls of the lower trachea. The tracheal lumen was narrowed by more than 70%. A severe mixed extrinsic compression and endoluminal obstruction pattern was noted. The remaining airways were normal except for an enlarged carina (Figure 2). The procedure lasted only 1 minute, during which the peak airway pressure increased to 80 cm H₂O but without hypoxemia or hemodynamic instability.

Figure 2 A, Flexible bronchoscopic view of the mass showing 70% obstruction of the airway lumen. B, Bronchoscopic view distal to the tumor shows patent airways and normal main carina.

Question 3: Had this patient undergone physiologic testing during his initial workup, which of the following patterns would have been expected on the flow-volume loop?

Answer: C

In cases of extrathoracic tracheomalacia, laryngomalacia, or vocal cord processes, the flow-volume loop pattern may be that of flattening of the inspiratory curve (Figure 3, A). This is due to the fact that intraluminal pressure during inspiration (PL) is lower than extraluminal pressure (Pm = atmospheric pressure) for the extrathoracic airway. Therefore, any obstruction in this airway segment will be made worse during inspiration and will cause limitation of the inspiratory flow. During expiration, however, to have an expiratory flow, the intraluminal pressure (PL) is higher than the atmospheric pressure (Pm), the extrathoracic airway will dilate, and the flow will be normal.

Figure 3 A, Dynamic (i.e., variable) extrathoracic obstruction with flow limitation and flattening of the inspiratory limb of the loop. B, Dynamic (i.e., variable) intrathoracic obstruction with flow limitation and flattening of the expiratory limb of the loop. C, Fixed upper/central airway obstruction with flow limitation and flattening of both inspiratory and expiratory limbs of the flow-volume loop. D, In the “airway collapse” pattern, maximal flow is reached quickly after expiration of a small volume of air. Following maximal flow, a large fall in flow occurs, although only a small volume is exhaled. In a subsequent phase, the flow rate falls very little during the remainder of expiration. This phase is responsible for the long plateau. PL, Intraluminal pressure; Pm, atmospheric pressure; Ppl, pleural pressure.

The opposite is true in cases of variable intrathoracic obstruction such as intrathoracic tracheomalacia. In this case, the obstruction is worsened during expiration when the pleural pressures (Ppl) exceed the intraluminal pressure (PL) (Figure 3, B), and there will be flattening of the expiratory curve of the flow-volume loop.

Our patient had a tracheal mass limiting airflow both during inspiration and during exhalation. The pattern on the flow-volume loop would likely have been that of blunting of both inspiratory and expiratory curves (Figure 3, C), the so-called square pattern. This pattern may be seen before spirometry yields abnormal results but may not be appreciated until the airway diameter is already narrowed to about 8 to 10 mm and is often masked in severe COPD.

The airway collapse pattern (Figure 3, D) is usually seen in severe COPD and may suggest excessive dynamic airway collapse. This flow-volume loop pattern suggests compression of the mainstem bronchi and trachea. The sudden drop in flow velocity occurs early during expiration when intrathoracic pressure is still increasing, as documented by esophageal pressure measurements. Because there is no reduction of force expelling air from the lungs, the sudden fall in velocity can be explained only by a sudden increase in resistance to airflow, which occurs because of collapse of the central airways. The small, relatively constant flow (i.e., plateau) that occurs after the sudden drop in velocity is consistent with air being forced through a narrow airway.

The case continues

This patient was married and had good social support. He had previously expressed his desire for diagnosis and was ready to consider all available treatment options, including mechanical ventilation, surgery, and other treatment modalities. He very likely had lung cancer and thus required tissue diagnosis. Alternatives presented to the patient’s wife included rigid bronchoscopy, flexible bronchoscopy with biopsy, and percutaneous needle aspiration of the pulmonary nodule.

Question 4: Which of the following reasons for recommending rigid bronchoscopy should be given during the informed consent process?

Answer: D

Patients with respiratory failure and malignant CAO treated by bronchoscopic intervention, who subsequently underwent definitive systemic therapy, were shown to have improved dyspnea and longer survival (median, 38.2 months; range, 1.7 to 57.0 months) compared with those who did not undergo bronchoscopic intervention (median, 6.2 months; range, 0.1 to 33.7 months; P < .001).⁷ Restoring airway patency also improves exercise capacity and dyspnea.⁷ In this study, a significant improvement in symptoms was noted in 94% of patients undergoing airway stent insertion, although ultimately 40% of patients required multiple bronchoscopic procedures. This raises concerns about the cost per quality of life-years gained in patients with advanced disease.⁸ The expense of palliative interventional procedures such as bronchoscopic laser resection and stent insertion, however, is probably small compared with the costs of repeated external beam radiation therapy or prolonged hospitalization in the intensive care unit. Rapid tissue diagnosis, restoration of airway patency, subsequent extubation and removal from mechanical ventilation, and discharge from the intensive care unit to a ward or even outpatient setting because of this single procedure likely result in considerable savings that positively impact health care costs and resource utilization.

Evidence that removal from mechanical ventilation in critically ill patients with airway obstruction and respiratory failure is possible because of interventional bronchoscopic procedures is limited but reproducible. Lo et al. successfully extubated 7 of 7 patients who were on mechanical ventilation for respiratory failure from malignant obstruction.⁹ Colt and Harrell successfully removed ventilatory support in 10 of 19 patients (52.6%) with malignant and benign obstruction,¹⁰ suggesting that when procedures were unsuccessful, immediate referral to hospice and comfort care was justified. Schaffer and Allen inserted metal stents in 6 patients with malignant CAO and in 2 with benign CAO, successfully extubating 6 of them 2 to 11 days later.¹¹ Furthermore, successful removal from mechanical ventilation has been associated with prolonged survival when systemic treatment is also administered (98 vs. 8.5 days).¹²

The case continues

During our dialogue with the patient’s wife, it was believed that the risks of further airway compromise and clinical deterioration were outweighed by the benefit of restoring airway patency with an ability to immediately diagnose the abnormality, wean the patient from mechanical ventilation, and offer systemic therapy. Although we planned to make the diagnosis on frozen section of the tumor removed from the airway, we could have also chosen to perform endobronchial needle aspiration (EBNA), brushing, or endobronchial forceps biopsy. In our experience, EBNA has a lower risk of bleeding than brushing or biopsy, and it provides immediate diagnosis when on-site cytologic examination is available. On-site cytology is not yet the standard of practice in many institutions; however, it may increase procedure-related costs, and, contrary to endobronchial biopsy, tissue architecture is not seen.¹³

Question 5: Had rigid bronchoscopic resection not been offered, which procedure would you have chosen to make a diagnosis in this patient?