Alfentanil

Study objectives: Surgery is the treatment of choice for symptomatic tracheal obstruction due to benign or malignant thyroid disease. In case of inoperability, or when surgery is refused, few therapeutic alternatives are available. Interventional bronchoscopic procedures have only been reported anecdotally. The objective of this study is to evaluate the results of interventional bronchoscopic procedures in the treatment of severe tracheal obstruction due to thyroid disease. Study design: Retrospective cohort analysis.

Setting: University hospital, tertiary referral center.

Patients: Thirty consecutive patients referred for bronchoscopic treatment of benign (n = 17) or malignant (n = 13) thyroid-related upper airway obstruction due to tracheomalacia, extrinsic compression, and/or tracheal ingrowth. Indications for bronchoscopic treatment were medical or surgical inoperability, prevention or treatment of tracheomalacia, and refusal of surgery. There were no procedure-related complications.

Interventions: Rigid bronchoscopy with dilatation, stenting and/or Nd-YAG laser treatment, and clinical follow-up.

Measurements and results: Subjective improvement, pulmonary function tests, early and late complications, and survival. In the benign group, immediate (100% relief of dyspnea) and long-term (88% relief of dyspnea) results were excellent after airway stenting (21 stents used in 17 patients). There was one unrelated death 1 week after stenting in a 98-year-old patient. There were 6% and 30% short-term and long-term complications, respectively, that could be managed endoscopically. In the malignant group, Nd-YAG laser treatment (n = 3) and stenting (n = 13) yielded immediate and long-term success in 92% of patients. There were 15% short-term and 8% long-term complications. Median survival time was 540 days.

Conclusions: Interventional bronchoscopic procedures including Nd-YAG laser treatment and stenting are valuable alternatives to surgery in inoperable thyroid-induced tracheal obstruction, or when surgery is refused.

Key words: airway stents; bronchoscopy; intrathoracic goiter; thyroid carcinoma; tracheal stenosis; treatment

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Various benign and malignant thyroid disorders can cause upper and central airway obstruction. Mechanisms of airway obstruction include extrinsic tracheal compression (eg, benign intrathoracic or substernal goiter), tracheal ingrowth (eg, thyroid cancer), tracheomalacia (eg, after thyroidectomy), vocal cord paralysis (eg, recurrent nerve paralysis after thyroidectomy), or a combination of the above.

The most frequent cause of thyroid-induced airway obstruction is the presence of a substernal (benign or malignant) goiter compressing the trachea, with or without associated tracheomalacia. (1) Invasive thyroid carcinoma can mimic the (compressive) symptoms of a substernal goiter, but is a less frequent cause of thyroid-induced airway obstruction.

Clinical or functional signs of airway obstruction due to thyroid enlargement are generally considered to be an absolute indication for surgical treatment, (2-5) even in elderly patients. (6) When surgery is contraindicated, suppressive treatment with levothyroxine or radioiodine can be considered in benign disease However, attempts to reduce multinodular or large goiters using suppressive dosages of thyroid hormone usually have little or no effect, (7) whereas results of radioiodine treatment of nontoxic and toxic goiters are somewhat better. (8,9) Treatment of differentiated primary thyroid cancer consists in total thyroidectomy followed by adjuvant radioiodine treatment and suppressive thyroxine therapy. External-beam irradiation and chemotherapy are not primary treatment modalities. (10,11) Finally, a variety of malignant tumors can metastasize to the thyroid gland, thus causing thyroid enlargement and upper airway compression.

In case of technically or medically inoperable patients with benign or malignant symptomatic airway obstruction, some form of symptomatic or palliative treatment should be considered. In these patients, bronchoscopic insertion of tracheal endoprosthesis (stents) may provide longstanding airway patency, as has been shown anecdotally in some case series (12) and case reports. (13,14) In this article, we present our experience with bronchoscopic airway stenting in a series of 30 consecutive patients with thyroid-induced airway obstruction.

MATERIALS AND METHODS

This is a retrospective cohort analysis of a series of 30 consecutive patients referred to the Interventional Endoscopy Clinic of the Academic Hospital AZ-VUB in an 8-year period for bronchoscopic treatment of severe airway obstruction caused by benign or malignant thyroid disease.

Patients

All patients bad symptoms of airway obstruction (stridor, dyspnea). Two patients also had hemoptysis. Patient characteristics are summarized in Table 1 (for benign disease) and in Table 2 (for malignant disease). Seventeen patients were treated for airway obstruction secondary to benign thyroid disease (9 men and 8 women; mean age, 78.4 [+ or -] 10.7 years [[+ or -] SD]; range, 61 to 98 years). Indications for interventional bronchoscopy in this patient group were acute stridor leading to respiratory insufficiency, refusal of surgical treatment by the patient, and/or medical or surgical inoperability.

Thirteen patients were treated for malignant thyroid involvement (primary and secondary) leading to tracheal obstruction (3 men and 10 women; mean age, 64.2 [+ or -] 18.6 years; range, 30 to 92 years). Indications for bronchoscopic treatment were local or general inoperability with progressively increasing stridor or acute respiratory insufficiency, tracheomalacia, or recurrence after previous surgery. All patients (or their kin) were completely briefed on the procedure, its possible results and complications, and gave consent to the intervention.

Patient Workup

Workup consisted of spirometry with flow-volume loop analysis, tomographic or CT imaging of the trachea and thorax, and flexible bronchoscopy. Pretreatment spirometric data were available in all but one patient who was intubated at the time of referral. Posttreatment spirometry was performed the day after therapeutic bronchoscopy (Tables 3, 4). Since the majority of patients were referred, long-term follow-up spirometry data were not available.

Bronchoscopic Procedures

All procedures were performed under general anesthesia in a dedicated operating room or laser-equipped bronchoscopy suite. Anesthesia was induced in the dorsal position using 1 to 2 mg/kg of propofol, 10 to 25 [micro]g/kg of alfentanil, and 0.5 mg/kg of atracurium. Two minutes after induction, the patients were intubated with a rigid bronchoscope or tracheoscope (models BT 101 and BT 200; Efer-Dumon; La Ciotat, France; or model 10317 EF; Storz; Tutlingen, Germany). Patients were ventilated with a high-frequency jet ventilator (AMS 1000; Acutronic Medical Systems; Jona, Switzerland) delivered via a side port of the bronchoscope. Anesthesia was maintained with IV propofol (4 to 6 mg/kg/h) and alfentanil (0.25 to 0.75 [micro]g/kg/h) according to the hemodynamic parameters of the patients. Fraction of inspired oxygen varied between 0.35 and 1.0, and was adjusted in function of the transcutaneous oxygen saturation level, and of the procedure to be performed; in case of use of Nd:YAG laser, fraction of inspired oxygen was lowered to [less than or equal to] 0.5.

Airway Dilation

The site of tracheal obstruction was carefully inspected. When indicated, biopsy specimens were obtained for pathologic examination using a rigid biopsy forceps. In every case, the trachea was gently dilated using balloon dilation (15) or rigid dilation using bronchoscopes of progressively increasing diameter. The distal margins of the stenotic process were visualized, and total length and diameter of the stenosis were recorded.

Debulking

In case of malignant ingrowth by tumor, endotracheal tumor tissue was first coagulated using the Nd-YAG laser (Medilas 2; MBB; Munchen, Germany) [power settings, 20 to 40 W; illumination time, 0.5 to 5 s; laser tip distance, 0.5 to 5 mm]. Small lesions were completely evaporated, whereas larger lesions were resected using the tip of the bronchoscope.

Stenting

In every case, airway patency was maintained by insertion of an endoprosthesis or stent. Its type, length, and diameter were determined after measurement of the length and postdilation diameter of the stenotic region. Stent types included polymer stents (Dumon; Novatech; Grasse, France; Tygon-Noppen; Reynder Medical Supply; Lennik, Belgium) and self-expandable nitinol stents (Ultraflex; Boston Scientific; Watertown, MA). Dumon stents were inserted through the rigid bronchoscope using a previously described technique. (16) Noppen-Tygon stents were inserted over the rigid bronchoscope using a plastic pusher tuber. (17) Ultraflex stents were inserted using the flexible insertion system of the manufacturer through the rigid bronchoscope. After stent insertion, a thorough inspection and bronchial cleanup were performed.

Discharge and Follow-up

All patients were discharged within 2 days after the procedure. All but four patients were referred from other centers, and were followed up clinically and endoscopically by their referring physician. Long-term follow-up data were obtained by telephone or e-mail contacts with the referring physicians. Subsequent treatment was performed when indicated. The four patients from our hospital were followed up clinically and endoscopically with fiberbronchoscope examination every 6 months.

Statistical Analysis

Demographic data are described as mean [+ or -] SD, and are compared using two-tailed Student t test and [chi square] analysis. Survival data are analyzed using the Kaplan-Meier method. Statistical significance is accepted at p < 0.05.

RESULTS

Patients with airway obstruction secondary to benign thyroid disease were significantly older (78.4 [+ or -] 10.7 years vs 64.2 [+ or -] 18.6 years) than the patients with malignant disease. There was no significant difference in gender between both groups. There were no procedure-related complications, and all patients could be discharged within 48 h after treatment.

Benign Group

Indications for bronchoscopic treatment in the benign group were medical or surgical inoperability or specific request by the surgeon (nine patients, 53%), refusal of surgery (five patients, 29%), tracheomalacia (two patients, 12%), and one patient with acute severe respiratory insufficiency with imminent respiratory failure (6%). Fifteen patients (88%) had large substernal goiters causing extrinsic compression of the trachea, 1 patient (6%) had combined extrinsic stenosis and tracheomalacia, and 1 patient (6%) had severe tracheomalacia occurring after thyroidectomy for a large substernal goiter.

In total, 21 stents were inserted in 17 patients (10 Dumon stents, 8 Tygon-Noppen stents, and 3 Ultraflex stents). Immediate symptomatic relief, as confirmed by spirometric improvement (Table 3), occurred in all. Improvement persisted in 15 patients (88%) during a mean follow-up period of 46.4 [+ or -] 34.4 months (range, 5 to 96 months). Endoscopic and CT images of a typical case (patient 9) are shown in Figure 1. One 98-year-old patient died 1 week after stenting, due to cardiac arrest. At the time of death, the airway was patent. Of the remaining 16 patients, 1 patient required stent replacement at 48 h followed by stent replacement again at 1 month. Two patients had stent migrations (three episodes) occurring at 5 to 17 months requiring stent repositioning or replacement. Two patients had granuloma formation (four episodes) requiring stent repositioning, replacement, removal, or additional treatment with the Nd-YAG laser. One patient had stent obstruction at 1 month requiring stent replacement. In this group of 16 individuals, 10 additional bronchoscopies were necessary to relieve complications. In addition, four patients subsequently underwent thyroidectomy, and all had their stents successfully removed, requiring four additional bronchoscopies. Thus, in the group of 17 patients with benign disease, 31 bronchoscopies were necessary to treat the initial or subsequent airway problem. All but one patient appeared to do well during the course of follow-up.

[FIGURE 1 OMITTED]

Malignant Group

Indications for bronchoscopic treatment in the malignant group were medical or surgical inoperability (10 patients, 77%), recurrence after previous surgery (2 patients, 15%), and tracheomalacia occurring after previous surgery (1 patient, 8%). Ten patients (77%) had purely extrinsic compression of the trachea requiring dilation and stenting, one of which with associated bilateral vocal cord paralysis. Three patients (23%) showed extrinsic tracheal compression associated with tracheal ingrowth, requiring Nd-YAG laser treatment prior to dilation and stenting. In every case, the site of tracheal ingrowth or compression was located at least 15 mm distal from the vocal cords. Hence, stents could be inserted sufficiently distal from the vocal cords to avoid cord irritation.

Fourteen stents were inserted in 13 patients (10 Dumon stents, 3 Noppen-Tygon stents, and 1 Ultraflex stent). Immediate symptomatic relief occurred in 12 patients as confirmed by spirometry (Table 4). In one patient, there was persistent stridor due to bilateral vocal cord paralysis, which was later treated by C[O.sub.2]-laser cordotomy. One patient had tumor recurrence requiring laser resection at 9 days and 20 days after the initial treatment. One patient had stent migration at 1 week requiring stent replacement. One patient had tumor recurrence at 18 months requiring laser resection and stent repositioning.

Median survival time (follow-up, 2 to 76 months) was 540 days. Six of 13 patients (46%) died because of cancer generalization and/or progression. All patients, however, were reported to have a patent airway at the time of death.

DISCUSSION

This is the first report of a large series of 30 consecutive patients with airway obstruction secondary to benign or malignant thyroid disease treated with interventional bronchoscopy techniques. In both benign and malignant diseases, excellent short-term and long-term improvements in symptoms and pulmonary function, together with an acceptable complication rate, were obtained. Information on long-term spirometric follow-up was not available in every patient. However, telephone and e-mail contacts with the referring physicians confirmed that initial improvements persisted during the follow-up. Despite the lack of face-to-face follow-up in every patient, this method allowed for sufficient retrieval of clinical follow-up data.

The incidence of airway obstruction secondary to thyroid enlargement varies widely in the literature, ranging from 16% (3) to 33%, (4) 60%, (5) and even 85% in smaller series, (9) probably because of differences in study population inclusion criteria (eg, nontoxic goiters only, or surgical series of patients who were already considered candidates for surgery). In general, pulmonary function tests including shape study of the maximal flow-volume curve are considered typical and sensitive estimates for upper airway obstruction, (9) although pulmonary function test result abnormalities seem to correlate poorly with clinical signs and symptoms (4) and with radiologic abnormalities on CT scan or radiograph. (18,19) The sensitivity of the flow-volume curve analysis for detecting airway obstruction due to goiter can be increased by performing the test in both upright and recumbent postures. (20) However, in every patient in our series in whom pulmonary function tests were performed, pulmonary function parameters were abnormal.

Two patients in the benign group had experienced acute respiratory insufficiency necessitating intubation and ventilation; this is a rare but dangerous event that can be due to concomitant events such as a mid-airway infection (21) or by sudden increases in thyroid volume due to, eg, intrathyroidal hemorrhage. (22-24) This is one of the reasons why active treatment of large substernal goiters is necessary. (23,24)

In five patients (four patients with benign substernal goiter, and one patient with follicular carcinoma of the thyroid), airway stents were inserted to prevent or treat airway collapse due to tracheomalacia after thyroidectomy. Stents were removed successfully in five patients at 6 months after thyroid surgery, and in one patient at 37 months. Although postoperative tracheomalacia has been described, (25) its incidence is low (one case in 116 thyroidectomies). (26) Therefore, the indication for preventive stenting can be questioned, even in patients with longstanding goiter, and a more conservative strategy awaiting extubation after thyroidectomy probably can be justified. Indeed, in one of our patients, stenting was successfully performed after diagnosis of postsurgical tracheomalacia.

Stent removal at 6 months after surgery could easily be performed in all patients since polymer stents were used. In general, use of easily removable stents is recommended in airway obstruction due to benign disease. (27) Therefore, in 14 of the 17 patients with benign substernal goiter, easily removable, polymer stents were used. In three patients, self-expanding metal stents were used. These stents are much more difficult to remove, but were chosen because of specific stenosis characteristics (stenoses of variable axis or diameter).

Interventional bronchoscopic techniques today are widely accepted in the palliation of malignant airway obstructions. (28,29) Although inoperable lung cancer by far is the most frequent indication of interventional bronchoscopy, several cases of tracheal compression or invasion by thyroid cancer have been successfully managed by bronchoscopic treatment. (13,14,30) A prospective study (31) of 16 cases of thyroid cancer treated with rigid bronchoscopy was published in abstract form. Laser treatment and stenting yielded good results in 9 of 16 patients (56%), whereas persistent dyspnea resulted in tracheostomy in 4 patients, cordectomy in 1 patient, Montgomery stent placement in 1 patient, and respiratory failure and death in 1 patient. In our series of malignant cases, bronchoscopic treatment was uneventful in nine patients (69%) and complications occurred in four patients (31%): laser repeat intervention in one patient (with good results), stent renewal and replacement in one patient (with good results), and of persistent stridor because of bilateral vocal cord paralysis in two patients requiring C[O.sub.2]-laser cordotomy. In one patient with combined tracheal stenosis and bilateral vocal cord paralysis, cordotomy should have been performed simultaneously with interventional bronchoscopy. Because of logistic reasons (the ear, nose, and throat surgical team with their C[O.sub.2] laser being unavailable at the time of referral), this young patient with imminent suffocation was offered bronchoscopy in an attempt to maximize airway patency. Cordotomy was performed 3 days later.

Main complications of airway stenting include colonization and infection, (32) which may lead to stent obstruction, stent migration, (33) and granuloma formation tit the proximal or distal ends of the stent. All of these complications have been observed in this series, but were newer life threatening and could be managed endoscopically. Stent obstruction by dried secretions is a frequent side effect of stenting. Patients are advised to inhale aerosolized saline solution twice daily. In case of foul breath, suggesting stent colonization, (32) inhaled tobramycin, 80 mg bid for 3 consecutive days, is prescribed. Finely, although repeated bronchoscopies were necessary in some patients to treat initial and subsequent airway problems, this was never believed to be a major burden in this group of patients treated for imminent suffocation.

We conclude that interventional bronchoscopic procedures can achieve long-term airway patency in the majority of patients with airway obstruction secondary to substernal goiter in whom surgical treatment is contraindicated or refused, as well as significant palliation and airway patency in patients with tracheal compression and/or ingrowth secondary to malignant thyroid disease refractory to, or awaiting secondary surgery or other (radioiodine) treatment.

ACKNOWLEDGMENT: The authors thank Leen Nechelput and Brenda Mees for secretarial assistance, as well as all referring colleagues.

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* From the Interventional Endoscopy Clinic and Respiratory Division (Drs. Noppen, Meysman, and Vincken), the Anaesthesiology Department (Dr. D'Haese), and the Endocrinology.. Department (Drs. Poppe and Velkeniers), Academic Hospital AZVUB, Free University of Brussels VUB, Brussels, Belgium.

Manuscript received January 7, 2003; revision accepted July 31, 2003.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: permissions@ehestnet.org).

Correspondence to: Marc Noppen, MD, PhD, FCCP, Interventional Endoscopy Clinic and Respiratory Division. Academic Hospital AZ-VUB 101, Laarbeeklaan B, 1090 Brussels, Belgium; e-mail: marc.noppen@az.vub.ac.be

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