Oxybuprocaine

Indications and Results

Study objectives: Bronchoscopic balloon dilatation (BBD) has become a valuable tool in the treatment of benign tracheobronchial stenoses. The objective of this study was to assess indications for and results of fiberoptic BBD in treating malignant lesions.

Design: One hundred twenty-six balloon dilatation procedures were performed in 78 patients with predominantly bronchial carcinoma. BBD was only performed when alternative modes of local treatment (eg, laser therapy or stent implantation) were not indicated or were inappropriate. Indications were symptomatic stenoses of the tracheobronchial tree: dyspnea or stridor (52%), retention pneumonia (15%), atelectasis (10%), retention of secretions (21%), or lung abscess (2%).

Results: Fifty-five percent of all procedures consisted of dilatations of tracheal or bronchial lesions (group 1). In 22% of procedures, a stent was dilated (group 2). In 13%, BBD was used to facilitate stent placement (group 3), and in 10% to enable the correct positioning of irradiation probes for brachytherapy (group 4). In group 1 and group 2, 2 of 2 lung abscesses resolved, 5 of 8 atelectases resolved, and 11 of 12 retention pneumonias resolved. Dyspnea improved in only 12 of 32 patients. No abscess recurred. Two pneumonias and two atelectases reappeared due to restenosis. Stent implantation and brachytherapy procedures were facilitated in 90% of cases. In 52% of cases, BBD was supported by high-frequency jet ventilation. Complications consisted of one fatal hemoptysis caused by a lacerated pulmonary artery, and minor bleeding not necessitating specific therapy.

Conclusions: Fiberoptic BBD is useful in the management of airway stents prior to and postimplantation, as well as in the placement of brachytherapy catheters. BBD is also successful in the resolution of poststenotic lung abscesses, retention pneumonias, and atelectases. (CHEST 2001; 120:43-49)

Key words: balloon catheter; balloon dilatation; bronchial carcinoma; bronchial disease; bronchial stenosis; bronchoplasty; bronchoscopy; interventional bronchoscopy

Abbreviations: BBD = bronchoscopic balloon dilatation; HFJV = high-frequency jet ventilation; PEFR = peak expiratory flow rate

In malignant tracheobronchial disease, stenoses of central airways are a common complication of endoluminal tumor growth.[1,2] Interventional bronchoplastic procedures, such as endobronchial irradiation,[3] laser therapy,[4,5] or stent placement,[6,7] also have the potential to induce tracheobronchial stenoses. When subsequent symptoms such as dyspnea, stridor, retention of secretions, or recurrent infection evolve, therapeutic interventions become necessary. A variety of endoscopic techniques, such as bougie dilatation,[8] Nd-YAG laser resection,[9] cryotherapy.[10] electrocautery,[11] and stent placement,[12,13] have been developed, since systemic therapy is not available or is ineffective. Bronchoscopic balloon dilatation (BBD) using angioplasty balloon catheters has been employed successfully in the treatment of tracheobronchial stenoses in children[14,15] and has met with variable success in adults,[7,16] although for treatment of stenoses in adults, reports[7,17-21] exist only in anecdotal form or for a small number of patients. In all reports, the stenoses were of benign origin. The method was considered safe and effective and involved the application of either flexible or rigid bronchoscopes.

In this article, we discuss 126 balloon dilatations of tracheobronchial stenoses in patients with malignant disease, performed primarily under local anesthesia and using flexible bronchoscopes exclusively. The objective was to evaluate indications, safety, and long-term results of fiberoptic BBD in the treatment of malignant disease.

MATERIALS AND METHODS

In this prospective trial, 78 consecutive patients underwent 126 BBD procedures. Informed consent was obtained from each patient. Age ranged from 28 to 84 years (mean [+ or -] SD, 62.3 [+ or -] 10.9 years). Bronchial carcinoma was the predominant underlying malignancy, accounting for 82% of cases. Eighty-eight percent of the bronchial carcinomas were stage III or stage IV disease.

Indications

Indications for interventional procedures were bronchial or tracheal stenoses, which had led to specific symptoms such as dyspnea or stridor (52%), retention pneumonia (15%), atelectasis (10%), retention of secretions (21%), or lung abscess (2%). Criteria for performing BBD instead of equally available alternative therapies, such as laser therapy, cryotherapy, or stent implantation, are listed in Table 1. Primarily exophytic stenoses were only dilated in preparation for self-expandable metal stents and when ablative therapies were contraindicated (eg, laser therapy in long and confusing stenoses with the risk of bronchial rupture). The indications for the dilatation of stents were insufficient unfolding of the prosthesis during placement or relevant compression by extrinsic tumor growth. Chemotherapy or radiotherapy were not considered alternative forms of treatment, since the onset of the therapeutic effect is delayed. In general, BBD was only performed when other interventional modes of therapy were either not indicated or when they could not have been successfully completed without the supporting role of BBD. BBD was repeated when a recurring stenosis was again symptomatic or when the recurrence of a stenosis was observed at follow-up bronchoscopy.

BBD Technique

Quantification of the stenoses was performed semiquantatively, according to Hauck et al[22] (Table 2). In 28% of patients, bronchography was performed to assess the grade of the stenosis, particularly its length, and to evaluate the poststenotic situation. Figure 1 shows a bronchography of two stenoses of the left upper lobe bronchi before and after BBD. The indication was the presence of a lung abscess due to retention. The lower lobe bronchus has already been supplied with a nitinol stent. A CT scan of the thorax, obtained within a maximum of 10 days prior to BBD, was available in 78% of the cases to further determine the character of the lesion. When it became obvious that the poststenotic region was not ventilated due to diffuse tumor growth, BBD was not performed. The choice of balloon size was based on the estimated caliber of the normal airway at the site of the lesion.

[ILLUSTRATION OMITTED]

Fiberoptic bronchoscopy was carried out with topical anesthesia alone or with IV sedation in combination with high-frequency jet ventilation (HFJV). The patient was placed in the supine position. Topical anesthesia was achieved by instillation of 10 to 15 mL of 2% oxybuprocaine nebulized in the spontaneously breathing patient. Premedication consisted of IV midazolam, 1 to 3 mg. HFJV was begun when the patient's respiratory function was markedly impaired or when an intraoperative impairment was to be expected. The decision whether to begin HFJV depended on the patient's clinical presentation, lung function, and results of blood gas analysis. HFJV was used principally when the trachea or another functional single airway was involved. In these cases, a 14F catheter was introduced transnasally into the trachea over a guidewire that was placed endoscopically as previously described.[23]

After endoscopic evaluation, skin markers specifying the limits of the stenosis were attached by means of fluoroscopy. A flexible, 0.035-inch guidewire (Meditech; Boston Scientific; Watertown, MA) was inserted through the bronchoscope and passed through the lesion. The bronchoscope was then withdrawn. Under fluoroscopic guidance, the balloon was advanced over the guidewire, approximately 1.0 cm beyond the distal limit of the stenosis.

We used regular PTA dilatation catheters (Cordis; Roden, The Netherlands, and Microvasive; Belmont, MA). The balloons had diameters of 4 to 18 mm and varying lengths of 20 mm or 40 mm. Generally, three balloon insufflations were performed for 10 to 30 s at 3 to 5 atm during each procedure. The balloon was insufflated with diluted water-soluble contrast medium (iopromide), allowing accurate control of the balloon position during dilatation. When the extent of the stenosis was greater then the length of the balloon, the stenosis was dilated in two or more stages, advancing the balloon toward the proximal margin of the stenosis. For dilatation of stents (Wallstent, Tantalum-Strecker-Stent, Nitinol-Stent; Boston Scientific, Watertown, MA), the balloon diameter chosen did not exceed the nominal stent diameter.

Lung Function Studies

Lung function studies were recorded before and after BBD, including [FEV.sub.1], peak expiratory flow rate (PEFR), FVC, airway resistance (Bodyscreen; Jaeger; Wurzburg, Germany), and arterial blood gas tensions (ABL500; Radiometer; Copenhagen, Denmark). Lung function data obtained within 72 h before and after BBD, respectively, were available for 42 patients.

Follow-up

Objective and subjective ventilatory function, radiographic imaging, and bronchoscopic findings determined the clinical success of BBD. In many procedures, bronchography was available before and after dilatation to assess lumen differences. Follow-up bronchoscopies were performed routinely every 12 to 24 weeks or when specific symptoms emerged. Patients who could not be followed up by bronchoscopy were not evaluated. Follow-up time ended when BBD was repeated within the same lesion or when an alternative means of local therapy other than BBD was initiated. BBD was considered successful when, at the time of evaluation, the grade of the stenosis still showed improvement.

Statistical Analysis

Lung function data are expressed as means [+ or -] SD. For comparison of two means, we used the Wilcoxon test for paired samples or the Student t test for paired samples, depending on the distribution. All p values were two sided, and a p value [is less than] 0.05 was considered significant.

RESULTS

Degree, quality, and anatomic location of the stenoses are detailed in Table 2. The majority of stenoses were caused by extrinsic compression of the airway by surrounding tumor. In a mixed exophytic/ extrinsic stenosis, the exophytic portion alone would not have justified an interventional procedure. Fibrous stenoses were found in five patients. Patients receiving BBD were classified into four groups. Group 1 received BBD alone (n = 29). In group 2, an already-implanted stent was dilated (n = 20), in five patients immediately after implantation. In group 3, BBD was used to prepare a stenosis for stent placement (n = 16); in the fourth group, BBD was performed when a brachytherapy catheter could not pass through a stenosis (n = 13). Twenty-seven patients received repeated BBDs (19 patients in group 1 and 8 patients in group 2).

Immediate Results of BBD

Table 3 displays the results immediately after BBD as judged by bronchoscopy. Seventy-nine percent of all stenoses improved in diameter. In group 3 and in group 4, 90% of BBD procedures were successful. Only in one patient did the stenosis appear so rigid and twisted that a Nitinol stent failed to unfold adequately even after the subsequent stent dilatation. In two patients, the brachytherapy catheter could still not be passed through the dilated stenosis. These stenoses were each located within the right upper lobe bronchus. Stent dilatations (group 2) revealed somewhat better immediate results than nonstented stenoses (group 1). Markedly better immediate results were achieved when we look at subgroups of group 1 with exclusively fibrous stenoses or stenoses pretreated with external and endoluminal radiotherapy (Table 4). When a stent was dilated immediately after implantation due to incomplete unfolding, BBD was successful in four of five patients. Lung function analysis demonstrated a small but significant increase in [FEV.sub.1], PEFR, [FEV.sub.1]/ FVC, and Pa[O.sub.2] within 72 h after BBD (Table 5). Best results were achieved in stenoses of the trachea or singular airways. The improvement in the grade of the stenosis, however, did not always correlate with changes in [FEV.sub.1] (r = 0.69; p = 0.24)

Long-term Results of BBD

Regarding long-term recanalization rates, only group 1 and group 2 were evaluated, since in the remaining patients BBD was not the definitive treatment modality. Within the average follow-up time, 43% of stenoses in group 1 and 52% of stenoses in group 2 maintained an improved diameter when compared to the predilatation status (Table 6). The subgroups of patients with fibrous stenoses or with preceding radiotherapy exhibited the best results (Table 4). All patients with fibrous stenoses also received combined radiotherapy before BBD. Minimum time interval between repeated dilatations in the same patient was 8 days (mean, 34 [+ or -] 19 days).

Clinical improvement did in fact correlate well with successful BBD. In group 1 and in group 2, 2 of 2 lung abscesses resolved, 5 of 8 atelectases resolved, and 11 of 12 retention pneumonias resolved. Dyspnea, however, was only improved in 12 of 32 patients. Retention of secretions decreased in 8 of 16 patients. During follow-up, no abscess recurred. Two retention pneumonias and two atelectases reappeared within the same lobe due to restenosis.

Complications

There was one fatal event during dilatation of a subtotal tumor stenosis of the left main bronchus that led to massive hemoptysis with subsequent asphyxia. Autopsy revealed laceration of a pulmonary artery branch that was surrounded and infiltrated by a massive tumor mass. Minor bleeding was observed in 41 patients, but did not necessitate specific therapy. In order to ensure adequate oxygenation, 52% of the dilatations were supported by HFJV. In 86% of these patients, IV sedation with propofol and alfentanil was additionally applied. Apart from two cases of bronchospasm with succeeding hypoxemia (arterial oxygen saturations of 71% and 74%, respectively) that necessitated treatment with inhaled [Beta]-agonists, no other complications occurred. Septic shock was the cause of death in one patient 5 days after BBD with stent implantation, but was not related to BBD. In this patient, repeated stent obstruction by viscous mucus prevented drainage and resolution of a retention pneumonia. At the time of data analysis, 20 patients (26%) were alive. In all other patients, minimum survival time after BBD was 25 days (mean, 126 days; range, 25 to 983 days).

DISCUSSION

BBD in adults has been used to treat tracheobronchial stenoses. However, reports on BBD have focused on benign disease, such as sarcoidosis, tuberculosis, or posttransplantation stenoses. Larger series consist of 14 patients[17] and 16 patients[19] with mean follow-up periods of 24 months and 21 months, respectively. Apart from case reports, there are no studies available on the use of BBD to treat malignant stenoses.

We performed 126 balloon dilatations in malignant obstructions. This report focuses specifically on the technique of flexible bronchoscopy since it is used by an increasing number of bronchologists. Of course, gentle mechanical dilation of airways using rigid bronchoscopes has been performed successfully in the past[24]; however, some authors[16] still use a balloon for dilatation even when a rigid bronchoscope is in place. Furthermore, the flexible method is particularly advantageous, eg, for use in areas not accessible by a rigid bronchoscope or in the dilatation of stents to prevent dislocation.

We found three situations where BBD was useful in the management of malignant tracheobronchial stenoses. One is the preparation of stenoses for endobronchial stent placement allowing for easier insertion and unfolding of the stent. This is a well-accepted practice in endoscopic stent implantation and has been recommended by various authors.[14,16,25] In high-grade stenoses, self-expanding stents cannot develop sufficient expansile force in order to achieve the desired lumen. Therefore, dilatation is a prerequisite for good results. Only in one patient did a stenosis reveal an unexpected stiffness and BBD failed to create enough airway lumen for successful stent placement. The same strategy applied to stents immediately after implantation. If the prosthesis did not adequately unfold, it could be opened with a balloon in order to expand to the desired diameter as well as to align with the bronchial wall.

An additional indication for BBD was in the placement of brachytherapy catheters, which was often impeded by high-grade stenotic lesions. In this case, the irradiation probe could not be placed through the stenosis, especially when the affected bronchus branched off at an unfavorable angle; BBD widened the stenosis, providing enough space for the probe to be placed within the desired bronchus. Only in two cases of upper-lobe stenoses did BBD fail to enable placement of the brachytherapy catheter when the catheter got caught in the rim of the stenosis and could not be pushed forward.

Obstructing tumor stenoses can also constitute an indication for BBD when alternative local treatment options are not desired or not possible. This is the case in extrinsic compression and complicated stenoses with uncertain anatomy, since this is a contraindication for ND-YAG laser resection or cryotherapy. Radiation therapy alone would not provide the immediate effect desired at the time of intervention, especially when poststenotic complications like pneumonias are to be treated. In the cases presented, stent implantation was problematic since the lesions were either located at the very proximal part of a main bronchus or at the orifice of an upper-lobe bronchus. In these locations, stent implantation is often problematic. In particular, the upper-lobe bronchi are often too short to allow efficient placement of a prosthetic device. The stent would have to protrude into the main bronchi in order to cover the lesion completely and to be held firmly in place. This could potentially result in the blockage of functioning airways due to retention and drying of secretions.[13]

When the above-mentioned conditions applied, BBD immediately improved the grade of stenosis in 79% of patients, and lung function parameters appear to substantiate this observation. However, the functional benefit was not very large, which may explain why only a few patients with dyspnea benefited from BBD. In addition, BBD provided sufficient ventilation for all lung abscesses and most retention pneumonias as well as atelectasis to resolve. The fact that in individual cases improvement in airway caliber did not always correlate with changes in lung function demonstrates that the clinical success of interventional procedures cannot be evaluated adequately by lung function alone. Specifically, peripheral stenoses are naturally not expected to have significant impact on lung function parameters. Their dilatation, however, can often solve the poststenotic problem.

Long-term results of BBD in malignant obstructions are very different from those in benign lesions. Patients with malignant lung disease often face a very limited prognosis, especially in our cohort with predominantly stage III and stage IV disease. Thus, interventional procedures are primarily of palliative character, whereas in benign stenoses, balloon dilatation is often a definitive treatment.[17] BBD was most successful after combined radiotherapy. This applied especially to all fibrous stenoses, which received transcutaneous and endoluminal irradiation prior to BBD. The etiology was most likely radiation bronchitis as described previously.[3] Perol et al[26] found fibrous stenoses after endobronchial irradiation in 56% of cases. Even if stenoses were not of fibrous character, long-term recanalization was improved as long as combined radiotherapy was completed prior to BBD. We assume that combined irradiation results in the formation of stable, solid necrotic tumor mass around the site of the stenosis, which leads to better local control of the dilated lesion. In all other patients, long-term results of BBD alone (group 1) were poorer, although none of the successfully treated lung abscesses recurred within the follow-up time. Atelectases and retention pneumonias reappeared in only a small number of patients, due to restenoses. This indicates that, like other interventional methods, BBD has the potential to treat symptomatic stenoses with reasonable success. Restenoses are a well-known phenomenon not only in BBD, but also in laser therapy and stent placement, with the need for repeated interventions. We performed repeated dilatations in a number of patients. They were performed when a stenosis was again symptomatic, but also when follow-up bronchoscopy revealed the recurrence of a stenosis. In the latter cases, it remains unclear whether this strategy prevented the recurrence of symptoms. Therefore, we cannot generally recommend the dilatation of a restenosis in the absence of specific symptoms.

Apart from fatal hemoptysis in one patient, complications were of only minor significance and were managed safely. The case of fatal hemoptysis could be attributed to a lacerated tumor-infiltrated pulmonary artery. Dilatation was attempted in order to recanalize the left main bronchus within a large tumor mass. Although the entry of the stenosis was clearly identified and bronchography revealed normal poststenotic bronchi, the guidewire could not be advanced to the periphery of the lung. In retrospect, we assume that guidewire and balloon catheter came to lie within the tumor tissue and not within the former bronchial lumen. We therefore recommend ensuring adequate intraluminal position of the balloon catheter before inflation. It remains questionable whether rigid bronchoscopy would have prevented the fatal outcome in this patient, considering the intensity of the bleeding. In spite of this complication, we believe that fiberoptic bronchoscopy represents a safe and effective instrument for performing BBD in malignant lung disease. Additionally, HFJV can be used when the patient's condition requires safe ventilation or when single airways are involved.

In conclusion, there are a number of indications for BBD. It is recommended for the restoration of airway lumen prior to endoluminal irradiation or stent placement when brachytherapy catheters or stents cannot adequately be placed. Another indication is bronchial stenoses when alternative treatment options, such as laser therapy or stent implantation, are not indicated or are inappropriate. BBD can then be used for the definitive treatment of fibrous as well as non fibrous symptomatic airway stenoses. Only patients with dyspnea do not respond well to BBD. However, in most cases, lung abscesses, retention pneumonias, and atelectases can be successfully treated with BBD. The rate of restenoses is high. Radiotherapy prior to BBD results in superior longterm recanalization. Apart from facilitating brachytherapy and stent placement, fiberoptic BBD is also beneficial when it is restricted to the treatment of stenoses that have caused inflammatory poststenotic complications or atelectases.

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(*) From the Klinikum Innenstadt, Medizinische Klinik, Ludwig Maximilians University, Munich, Germany.

Manuscript received October 25, 1999; revision accepted January 3, 2001.

Correspondence to: Hubert Hautmann, MD, Klinikum Innenstadt Medizinische Klinik, Ziemssenstr.1, D-80336 Munchen, Germany; e-mail: hautmann@medinn.med.uni-muenchen.de

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