in the Treatment of Re g actory Airway Strictures

Endotracheal Cryothera y in the Treatment of Re g actory Airway Strictures Bradley M. Rodgers, M.D., Farhat Moazam, M.D., and James L. Talbert, M.D. ABSTRACT In 1977 we reported the successful use of endotracheal cryotherapy in the treatment of experimental tracheal strictures. This technique has now been employed in the treatment of 29 refractory airway lesions in 27 patients ranging in age from 3 months to 42 years. The technique utilizes a nitrous oxide cryoprobe measuring 3 mm in diameter and 43 cm in length. The tip of the probe is applied directly to the stricture through the endoscope and cooled to -80 C for 45 seconds. On removal of the probe, the frozen tissue is resected with biopsy forceps. Cryotherapy has successfully relieved the airway strictures in 20 of the 24 lesions in which treatment was completed. Fifteen patients have been successfully extubated. The technique of endotracheal cryotherapy has proved helpful in the management of selected patients with refractory airway strictures. The past decade has witnessed remarkable advances in our understanding of the etiology and therapy of airway strictures. The landmark studies of Grillo, Dignan, and Miura [l] and others [2] have brought into focus the importance of proper management of endotracheal tubes and other artificial airways in reducing the incidence of acquired strictures. Nonetheless, with the expansion of intensive care capabilities, both thoracic and pediatric surgeons are caring for an increasing number of patients with congenital or acquired airway strictures. In 1977 we reported experimental studies demonstrating the efficacy of endotracheal cryotherapy in the treatment of airway strictures [3]. On the basis of that work, a clinical trial was instituted for the treatment of refractory airway strictures. The present report outlines the results of that trial and the current status From the Departments of Surgery, University of Florida, Gainesville, FL, and University of Virginia, Charlottesville, VA. Accepted for publication Mar 30, 1982. Address reprint requests to Dr. Rodgers, Box 181, Department of Surgery, University of Virginia Medical Center, Charlottesville, VA 22908. of endotracheal cryotherapy for the treatment of these lesions. Materials and Methods Between July, 1976, and March, 1981, 29 airway lesions in 27 patients were treated with cryotherapy. The patients ages ranged from 3 months to 42 years with a predominance of patients in the younger age group. Only 3 patients in this entire series were older than 25 years of age at the time of cryotherapy. This fact predominantly reflects bias in referral, as the authors practice is primarily in pediatric surgery, but it may also indicate the higher incidence of airway obstruction in young patients. Initially, patients were accepted for endotracheal cryotherapy only after more conventional and less invasive modalities had failed to bring relief of the airway obstruction. All these patients had undergone multiple previous attempts at airway dilation with or without the concomitant use of submucosal steroid injection, and many had undergone the use of subglottic stents without success. All patients but 1 had required placement of a tracheostomy for maintenance of a satisfactory airway; indeed, we have been somewhat reluctant to use endotracheal cryotherapy in patients without a tracheostomy, especially in younger children, because of the swelling it induces. In the past three years we have recognized that cryosurgery is the treatment of choice for certain airway lesions, particularly fibrogranulation tissue forming on the proximal border of a tracheostomy, and we have employed it as the primary therapy for this lesion. The preoperative evaluation of all these patients included an assessment of the airway with various radiological techniques. Posteroanterior and lateral chest roentgenograms and airway cinefluoroscopy usually were sufficient to demonstrate the extent of the strictures and to rule out concomitant tracheomalacia, but xeroradiography was utilized in several older 52 OOO3-4975/83/010052-06$01.50 0 1982 by The Society of Thoracic Surgeons

53 Rodgers, Moazam, and Talbert: Endotracheal Cryotherapy for Airway Strictures patients with proximal strictures to delineate the anatomy of the strictures more adequately. More recently, computerized axial tomography has been employed to gauge the extent of airway strictures in some patients. This modality has been especially helpful in evaluating more distal tracheal strictures as well as those of the proximal mainstem bronchi. Tracheography has not been employed in any of the patients in this study, as these other, less invasive means have been sufficient to define the airway lesion. The cryosurgical probe* employed for these procedures is an instrument designed specifically for use through the pediatric endoscope. The cryoprobe measures 43 cm in length and 3 mm in outside diameter, with an angled shaft to allow direct visualization during use. The entire shaft, except for the distal 1 cm, is insulated to avoid cooling of the adjacent structures. The cryoprobe uses nitrous oxide as a coolant source, relying on the Joule-Thomson effect (the cooling of a gas upon sudden expansion from a high- to a low-pressure region) to reach temperatures of -80 C within seconds of the probe's activation. The temperature of the tip of the cryoprobe is monitored continuously by an internal thermocouple. The precise operative technique for endotracheal cryotherapy has been described in detail elsewhere [4]. General anesthesia has been employed in all the patients, primarily to allow for careful examination and precise manipulation within a quiet airway. The area of narrowing is visualized with either the operating laryngoscope or bronchoscope, and the proximal and distal airway is evaluated for the presence of tracheomalacia. The tip of the cryoprobe is passed through the endoscope and placed directly on the area of maximal narrowing, and the instrument is cooled to -70" to -80 C for 45 seconds. After thawing, the cryoprobe is removed and the frozen tissues are resected with angled cup biopsy forceps. Several freezebiopsy cycles are usually necessary to relieve approximately 180 degrees of the circumference of the stricture; then the base of this area is injected with 1 ml of triamcinolone acetonide *Frigitronics of Connecticut, Inc., Shelton, CT 06484. (Kenalog) (40 mglml). All patients underwent endoscopy at four- to six-week intervals, and further cryotherapy was applied as necessary. When complete relief of the airway obstruction had been demonstrated by endoscopy, the patients were extubated. Follow-up endoscopy was repeated at four weeks and three months after extubation to assure continued relief. Results For the purposes of this analysis, the obstructions to the airway were divided into three anatomical locations: subglottic, including those strictures encountered between the vocal cords and the inferior border of the cricoid cartilage; tracheal, including those strictures between the cricoid cartilage and tracheal bifurcation; and mainstem bronchi, including those strictures distal to the carina. Subglottic Stenosis Sixteen lesions treated by endotracheal cryotherapy were in the subglottic region. Six were thought to be of congenital origin, all in infants symptomatic from birth and requiring tracheostomies for airway management. Each of these infants had cryotherapy instituted in the first year of life after dilations had failed to relieve the obstruction. The remainder of the subglottic stenoses resulted from endotracheal intubation. The ages of the patients with acquired lesions ranged between 6 months and 30 years. In this entire group there were 4 deaths during the cryotherapy treatment interval. Three were in infants less than 6 months old who had congenital lesions, and were caused by severe associated cardiac anomalies unrelated to the therapy for their airway strictures. In the fourth case, a subglottic web had been nearly completely relieved by two treatments with cryotherapy but the patient died at home with a tracheostomy obstruction. One patient with acquired subglottic stricture was lost to follow-up during the treatment interval. Of the remaining 11 patients, 6 (55%) have been successfully relieved of their airway obstruction and have been extubated (Fig la, B). The follow-up period after extubation in these patients extends from 1 to 6 years (me-

54 The Annals of Thoracic Surgery Vol 35 No 1 January 1983 A B Fig I. (A) Lateral xeroradiograph of a 23-year-old woman with an acquired subglottic stricture (arrows). (B) After two applications of cyotherapy, the patient was successfully extubated. Four months later the lateral xeroradiograph shows a widely patent subglottic airway. dian, 4 years), and in no case has there been evidence of recurrence of the subglottic narrowing. In 3 other cases (27%), the area of airway narrowing has been completely relieved by cryotherapy but the patients remain intubated. Severe tracheomalacia has prevented successful intubation in 2, and in the third, neurological impairment has delayed extubation. The follow-up period in these patients has ranged between 1 and 4 years (median, 2 years) without endoscopic evidence of recurrence of the strictures. The 9 patients in whom subglottic strictures have been successfully relieved by cryotherapy have required an average of 2.7 (range, 2 to 4) cryosurgical resections. In 2 patients with subglottic strictures, cryosurgery has been unsuccessful in relieving the airway obstruction. Both patients (6 and 9 years of age) had extensive acquired strictures extending from immediately beneath the vocal cords to the inferior border of the cricoid cartilage; both await further growth for more extensive laryngeal procedures. Tracheal Strictures Ten patients have been treated with cryotherapy for tracheal strictures. The ages of these patients ranged between 1 year and 42 years, and all their lesions were acquired. Three patients were treated for fibrogranulation tissue forming on the proximal border of the stoma of a tracheostomy. In each case this tissue was easily resected with a single application of cryotherapy, and we now consider this the optimal method of treatment for these obstructions. Another patient had fibrogranulation tissue forming in the distal trachea secondary to a chronic foreign body. As with the more proximal lesions, this lesion responded to a single application of cryotherapy. Of the remaining patients, 5 had tracheal strictures secondary to endotracheal intubation and in 1 patient the cause of the stricture could not be determined.

55 Rodgers, Moazam, and Talbert: Endotracheal Cryotherapy for Airway Strictures A Fig 2. (A) High-penetration anterior chest radiograph of a 15-year-old boy with an acquired tracheal stricture (arrows) stented open with a tracheostomy tube. (B) After two applications of cyotherapy, the patient was successfully extubated. Three months later the anterior radiograph revealed a widely patent airway (arrows). Nine patients have been successfully extubated, with follow-up periods ranging between 2 and 6 years (median, 3 years) after removal of the tracheostomy (Fig 2A, B). In no case has there been any endoscopic evidence of recurrence of the stricture. The patient with the idiopathic tracheal stricture has had the lesion successfully treated with 2 applications of cryotherapy but is still undergoing therapy for a coexistent stricture of the left mainstem bronchus. In the 6 patients treated with cryotherapy for true tracheal strictures unassociated with fibrogranulation tissue, an average of 2 applications of cryotherapy (range, 1 to 4) has been necessary to achieve relief of airway obstruction. The importance of the absence of coexistent tracheomalacia in the successful outcome of these patients is illustrated by one of our patients with a tracheal stricture. An 18-year-old woman required brief endotracheal intubation following a suicide attempt B with an overdose of sleeping medication. Within two weeks of extubation, she developed respiratory stridor and was noted to have a severe stricture at the junction of the middle and distal thirds of the trachea. Emergency tracheostomy and dilation were performed, but attempts at repeated dilation proved unsuccessful in relieving the stricture. The lesion was treated by cryotherapy on 4 occasions with complete relief of the stricture, but airway obstruction secondary to localized tracheomalacia continued. Extubation proved unsuccessful, and the patient underwent resection of five tracheal rings. After this operation, she was extubated for approximately six weeks when a recurrent stricture developed at the anastomotic line. This lesion was treated with 2 applications of cryotherapy with resultant complete relief; she has now been extubated successfully for 18 months without evidence of recurrent stricture or respiratory compromise. Mainstem Bronchi Strictures Three patients have been treated for strictures of the mainstem bronchus. In an 18-month-old infant, a stricture of the left mainstem bronchus thought to be secondary to irritation from a tracheostomy tube was completely relieved by

56 The Annals of Thoracic Surgery Vol 35 No 1 January 1983 2 applications of cryotherapy. Although this patient is still intubated because of severe tracheomalacia, there has been no evidence of recurrence of the left mainstem stricture in the six years subsequent to therapy. A 29-year-old patient is currently undergoing cryotherapy for a left mainstem stricture of undetermined etiology. After 3 applications of cryotherapy, the lumen of the left mainstem bronchus has been increased from 1.0 to 6.5 mm. The third patient with a left mainstem stricture had a combination of fibrous stricture and bronchomalacia associated with severe cardiomegaly. Cryotherapy was unsuccessful in relieving the area of obstruction, and the patient subsequently died from cardiopulmonary insufficiency. Comment The application of supercooled temperatures to living tissues has intrigued physicians for centuries. The ability of locally applied cold to relieve pain and stop bleeding was known to the ancient Egyptians. James Arnott [5], in the early nineteenth century, advocated the use of cryotherapy in a therapeutic manner for the treatment of cancer. In the last decade, many sophisticated studies have demonstrated that living tissue is susceptible to cryonecrosis and that cell death occurs at tissue temperatures in the region of -15 C [6]. The use of cryotherapy for treatment of superficial disorders has demonstrated that this modality has several properties potentially useful for its endotracheal application. When cryotherapy is applied to the skin, healing is extremely rapid and is not accompanied by fibrosis. In addition, temperatures in the range of 0" to -15 C induce arterial and venous spasm, and thus minimize local blood loss. This last property has been especially important for the endotracheal use of cryotherapy; in none of our patients did we encounter any major bleeding during the use of this modality. Experimental studies from our laboratory and elsewhere have demonstrated a remarkable resistance of the trachea to profound cryotherapy [3, 71. Following application of temperatures of -80 C for 60 seconds to the tracheal epithelium of experimental animals, a superficial ulcer forms within 48 hours but is completely reepithelialized within four days. The initially regenerated epithelium is a simple columnar layer, but within six weeks it has differentiated to a more normal-appearing tracheal epithelium. Studies by Neal and associates [8] have demonstrated cytolysis of the chondrocytes of the tracheal cartilage in response to cryotherapy applied to the external surface of the trachea, with complete recovery of the architecture of the cartilage within six weeks of cryoinjury. The results of these experimental studies confirmed the safety and efficacy of this modality, and we instituted clinical trials of endotracheal cryotherapy. Acquired and congenital strictures of the subglottic region present some of the most difficult of airway problems to manage. Initial therapy for these obstructions should progress from simple graded dilation to dilation procedures with injection of steroid medication or with the addition of subglottic stenting. Most patients with mild to moderate subglottic airway narrowing will respond to these relatively simple maneuvers. More refractory subglottic strictures have traditionally been treated with a variety of operative procedures, most of which involve extensive laryngotomy and laryngoplasty. These operations are fraught with complications, and there remains concern that they may interfere with the subsequent growth of the larynx in young children. Endotracheal cryotherapy offers an attractive alternative to these more invasive operative procedures. In our experience, the use of this technique has not been followed by any complications. Although our follow-up period is relatively short, it is unlikely that this procedure will interfere with laryngeal growth, as it does not involve injury to the laryngeal cartilage or insertion of foreign material. Our success in relieving the obstruction in 9 of the 11 surviving patients with subglottic stenosis indicates that the technique can be successfully employed even for extensive subglottic strictures. The high mortality in the group of small infants with congenital strictures has led to our current recommendation that cryotherapy not be instituted until life-threatening coexistent anomalies have been treated.

57 Rodgers, Moazam, and Talbert: Endotracheal Cryotherapy for Airway Strictures Many experimental and clinical studies have demonstrated that surgical resection of tracheal strictures can be performed with low morbidity and mortality rates. Nonetheless, pediatric surgeons have been somewhat hesitant to employ these techniques in young children because of the extent of the operative procedure required and concern about recurrence of the stricture with growth of the patient. In our series, endotracheal cryotherapy has been uniformly successful in relieving tracheal obstructions in children and adults. It is important to note that we have been selective in eliminating from consideration for cryotherapy those patients with extensive tracheomalacia noted on airway fluoroscopy or endoscopy. Grillo and others have pointed out the frequent loss of cartilaginous support in patients with acquired tracheal strictures; we believe that these patients are not candidates for endotracheal cryotherapy but should have a formal tracheal resection. Our experience suggests that endotracheal cryotherapy may be successfully employed for the occasional stricture that recurs after tracheal resection. Strictures of the mainstem bronchi, although very uncommon, do not lend themselves to standard resectional therapy. Endotracheal cryotherapy was successful in relieving these obstructions in 2 of 3 patients in whom we have attempted this form of therapy. The cryoprobe is sufficiently narrow to pass down either mainstem bronchus to treat these more distal strictures. Endotracheal cryotherapy offers a useful adjunctive modality for the treatment of airway strictures. The equipment employed is simple and relatively inexpensive. The technique itself is safe and may be easily performed by physi- cians familiar with endoscopic techniques. Cryotherapy allows for precise resection of airway strictures in a bloodless field. On the basis of our clinical results, we believe that endotracheal cryotherapy should be employed for airway strictures refractory to simple dilation or to dilation and stenting, prior to consideration of formal tracheal resection. In some situations, especially when fibrogranulation tissue has formed in response to a foreign body within the trachea, cryotherapy appears to be the treatment of choice and should be employed early. References 1. Grillo HC, Dignan EF, Miura J: Extensive resection and reconstruction of the mediastinal trachea without prosthesis or graft: an anatomical study in man. J Thorac Cardiovasc Surg 48:741, 1964 2. Fearon B, Colton R: Subglottic stenosis in infants and children: the clinical problem and experimental surgical correction. Can J Otol 9:281, 1972 3. Rodgers BM, Rosenfeld M, Talbert JL: Endobronchial cryotherapy in the treatment of tracheal strictures. J Pediatr Surg 12:443, 1977 4. Rodgers BM, Talbert JL: Clinical application of endotracheal cryotherapy. J Pediatr Surg 13:662, 1978 5. Amott J: On the Present State of Therapeutical Injury. Brighton, King, and London, Churchill, 1845, p 35 6. Smith JJ, Fraser J: An estimation of tissue damage and thermal history in the cryolesion. Cryobiology 11:139, 1974 7. Gorenstein A, Neal HB, Sanderson DR: Transbronchoscopic cryosurgery of respiratory strictures. Experimental and clinical studies. Ann Otol Rhino1 Laryngol 85:670, 1976 8. Neal HB, DeSanto LW, Sanderson DR, et al: Cryosurgery of respiratory strictures. I. Cryonecrosis of trachea and bronchus. Laryngoscope 83:1062, 1973