Duchenne muscular dystrophy

Study objectives: Autopsy evaluation of tracheobronchomalacia (TBM) in patients with Duchenne muscular dystrophy (DMD) who were receiving long-term ventilation through uncuffed tracheostomies.

Design: Necropsies were performed in seven patients with DMD who had received positive-pressure ventilation through uncuffed tracheostomies for a duration of 5 to 30 years.

Setting: Rehabilitation facility affiliated with a university medical center.

Results: The range of peak airway pressures sustained during ventilation by all the patients was 23 mm Hg to 36 mm Hg. Bronchoscopy (which was performed in four of the five patients) detected tracheomalacia in only one of the patients. Five of the seven patients demonstrated variable degrees of airway malacia. Two patients also had tracheal perforations, one of which resulted in a fatal hemorrhage from a tracheovascular fistula.

Conclusions: Given enough time, patients receiving positive-pressure ventilation can develop airway thinning and dilation even without the use of an inflated tracheostomy cuff. There is also a potential for tracheal erosion into an adjacent artery that can lead to fatal hemorrhage. Such findings also have implications for individuals receiving noninvasive positive-pressure ventilation, who could develop TBM as a result of the continuous cycling pressures on the airway wall.

Key words: Duchenne muscular dystropy; mechanical ventilation; tracheobronchomalacia; tracheostomies

Abbreviations: DMD = Duchenne muscular dystrophy; NIPPV = nasal intermittent tracheal positive pressure; RLANRC = Rancho Los Amigos National Rehabilitation Center; TBM = tracheobronchomalacia

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Tracheobronchomalacia (TBM) refers to weakness of the tracheal and bronchial walls and the supporting cartilages. Primary TBM results from immature tracheobronchial cartilages occurring in isolation or in association with congenital conditions such as heart disease or esophageal fistulas. Secondary TBM results from the degeneration of previously healthy cartilage and is associated with extrinsic vascular compression, bronchial neoplasms, recurrent bronchitis, gastroesophageal reflux, long-term cuffed intubation, and tracheostomy. (1,2) The weakness of the trachea and bronchial walls is believed to cause abnormal flaccidity and collapse, which results in inefficient cough, retained secretions, air trapping, and recurrent bronchopulmonary infections. Most causes of TBM that are associated with long-term ventilation have been described in infants or young children of school age. (3) The duration of positive-pressure ventilation in these patients has been from a few weeks to a few months. Such reports in ventilated adults are even less common, and the duration of ventilation also has been described in terms of months. (4) In addition to TBM, tracheal erosion is a common complication of patients with chronic tracheostomies. Most often, TBM is associated with repeated endotracheal suctioning and tube movement. (5) Rarely, tracheostomies have been associated with fatal perforation and hemorrhage, usually originating from an adjacent subclavian or innominate artery. (6)

Following the placement of a cuffed tracheostomy tube, most patients with neuromuscular disease who are to receive long-term ventilation are changed to an airway without a cuff to facilitate comfort and speech. (5) Until now, it has been assumed that tracheal complications such as tracheal stenosis and TBM have been associated mainly with the constant pressure of the inflated cuff on the tracheal wall. (3,4) There are no reports of TBM in adult patients receiving long-term ventilation through an uncuffed tracheostomy. We describe the autopsy findings of TBM in five patients with Duchenne muscular dystrophy (DMD) who had received long-term ventilation for many years (even decades) while using an uncuffed tracheostomy. In addition, two of the patients developed tracheal perforations, one of which led to fatal hemorrhage.

MATERIALS AND METHODS

Rancho Los Amigos National Rehabilitation Center (RLANRC) is a teaching facility of the University of Southern California that has provided care for patients with neuromuscular and chest wall disorders with respiratory complications. Many of these patients included those with DMD, most of whom lived in the community. A small group of patients with DMD lived for most of their lives at RLANRC because of the unavailability of community resources. Individuals who received respiratory assistance were given tracheostomy-positive ventilation long before noninvasive ventilation became a feasible alternative for long-term ventilation. (7,8) Patients originally began receiving assisted ventilation because of progressive respiratory failure from DMD or pneumonia (Table 1).

After the resolution of the acute respiratory event that necessitated the tracheostomy, the cuff was intermittently deflated for increasingly prolonged periods until patients were able to tolerate ventilation with the cuff fully deflated all the time. They were then switched to an uncuffed tracheostomy to facilitate comfort and speech. This was achieved a few days after the placement of the tracheostomy. Only during acute respiratory events, such as pneumonias, atelectasis, or congestive heart failure, were tracheostomies changed to those with inflated cuffs. These periods would range from a few days to several weeks. Until around 1980, tracheostomies were made of metal. After that date, the tracheostomies were made of a plastic material. Patients were able to speak with these tracheostomies in place without the use of a one-way valve. All patients received ventilation in the volume-cycled mode with a portable ventilator (PVV, PLV-100, or PLV-102; Lifecare/Respironics; Murrysville, PA; or Companion 2801; Nellcor Puritan-Bennett; Pleasanton, CA). Continuous humidification was provided with humidifiers that were heated to near body temperature and mounted on the portable ventilators.

RESULTS

The adult chest medicine service at RLANRC observed approximately 75 respiratory impaired individuals with myopathies who were [greater than or equal to] 18 years of age between 1957 and 1995. During this period, approximately 30 ventilator-dependent patients lived at the facility for variable lengths of time because of the unavailability of community resources. The autopsy records were reviewed for seven patients with DMD who died after having lived at the facility for many years. All patients had spinal deformities. Five of these seven patients (listed in Table 1) were found to have varying degrees of tracheal malacia (with or without bronchial malacia). The causes of death included ventilator-associated pneumonia and cardiomyopathy. The clinical and pathologic aspects of these five patients are summarized in Table 1. The remaining two patients did not demonstrate tracheal or bronchial malacia at autopsy.

Chest roentgenograms demonstrated tracheal dilation (with an uncuffed tracheostomy) in only one of five patients (patient 5; Table 1). Bronchoscopy (three fiber-optic and one rigid) was performed to evaluate airway obstruction in four of five patients who were found to have TBM at autopsy. Patient 4 was found to have a long segment of invagination of the posterior tracheal membrane, which gave the appearance of a polypoid diverticular structure. Patient 1, who underwent bronchoscopy at the time of the revision of his tracheostomy was found to have stenosis from granulation tissue. A false passage also was noted below the tracheostomy site in the anterior wall. In addition to a patulous stoma and proximal trachea, patient 5 was noted to have erosions and edema at the level of the tip of the tracheostomy. No bleeding was observed at the time, however. Patient 2 underwent repeated bronchoscopy for the evaluation and management of secretions. His posterior tracheal wall was noted to bulge inward during the expiratory cycle of ventilation.

Sections of the trachea taken from patient 4 at the postmortem examination showed the focal absence of the tracheal cartilage, with replacement by the predominantly firm tan-gray fibrous tissue (Fig 1). A microscopic examination confirmed the absence of cartilage in these sites, with the fibrous tissue composed of collagen and mature fat (Fig 2). The border of the intact cartilage and this fibrous tissue was distinct, without an associated inflammatory component involving the cartilage.

[FIGURES 1-2 OMITTED]

Two patients exhibited tracheal perforations at autopsy. Patient 1 had two perforations. One perforation was posterior and localized to the periesophageal and adjacent mediastinal regions. A second, anterior, perforation, 4.5 cm inferior to the tracheostomy site, communicated directly with the innominate artery at its bifurcation point into the right common and subclavian arteries. This perforation was responsible for the patient's intratracheal hemorrhage, which was the immediate cause of death. In patient 5, the tracheal mucosa was noted to be markedly congested and somewhat eroded at the site of a small vessel invading the wall of the trachea. This small vessel, the ostium of which was 1 mm in diameter, arose from the junction of the innominate and right carotid arteries. A probe inserted through the vessel showed that it infiltrated directly into the hemorrhagic region of the lower trachea, 2 mm from its origin. None of our patients were found to have tracheal stenosis or tracheoesophageal fistulas.

DISCUSSION

The key findings in this clinicopathologic study are: (1) the development of acquired tracheobronchial malacia in some adult patients with DMD after many years of tracheostomy positive-pressure ventilation, (2) the development of TBM despite the use of uncuffed tracheostomies, and (3) the occurrence of fatal hemorrhage in some patients. The severity of the symptoms of TBM depends on the location, length, and severity of the abnormal airway segments. (9) Some patients with severe disease respond favorably to conservative measures including oxygen, endotracheal suctioning, postural drainage, and positive end-expiratory pressure through a tracheostomy. At least four of our five patients (patients 1, 2, 4, and 5) required frequent tracheal suctioning (ie, every 2 to 4 h) to clear secretions and relieve dyspnea.

All of the patients described here were receiving long-term ventilation through uncuffed tracheostomies. In only one of our patients, in whom TBM was found at autopsy (patient 5), was there radiographic evidence of abnormal tracheal dilation. Thus, the chest roentgenogram was unreliable in detecting airway widening. In patient 5, because of the patulous stoma and recurrent wound breakdown, an attempt was made to ventilate the patient with an uncuffed flexible metal tracheostomy. The use of this device did not result in wound closure or prevent the terminal hemorrhage. The direct cause of the vascular erosion was not clear but was in some way related to the markedly enlarged tracheostomy site. A small outflow vessel from the innominate artery exhibited direct communication with the hemorrhagic region and was the site of the terminal bleeding. The presence of the vessel at the site may have been coincidental or it may have contributed to the weakening of the already compromised tracheal wall.

It is not known at what airway pressures and over what period of time tracheobronchial damage occurs even with the use of uncuffed tracheostomies in older children or young adults with DMD who are receiving assisted ventilation. Barret et al (10) reported a higher incidence of tracheomalacia in 36 children with burns (most of whom had inhalation injuries) who had required airway pressures of > 50 cm [H.sub.2]O for > 10 days. Law et al (4) described 81 patients with long-term tracheostomies (mean duration, 4.9 months) who were examined via fiberoptic bronchoscopy prior to decannulation. Twenty-three percent of their patients had TBM. Their study did not report airway pressures. None of our patients' airway pressures approached the values of the patients in the study by Barret et al, (10) but our patients had received tracheostomy positive-pressure ventilation for many years. Recurrent tracheobronchial infections also could have led to chronic inflammation, weakening, and atrophy of the longitudinal elastic fibers with thinning of the muscularis mucosa, resulting in the dilation of the membranous and cartilaginous portions of the trachea and main bronchi. This increased compliance of the wall allows the development of broad diverticulum-like protrusions of redundant musculomembranous tissue between the cartilaginous rings. (11) The myopathic involvement of the tracheal muscularis also could contribute to the weakening and dilation of the wall. The use of pressure-controlled ventilation instead of volume-cycled ventilation may prevent tracheal complications, although ventilation may need to be adjusted to compensate for the uncuffed tracheostomy.

These findings also have implications in patients who receive noninvasive positive-pressure ventilation (NIPPV), which is currently the form of ventilation advocated in neuromuscular and chest wall disorders. (8,12) It is now possible, with appropriate nasal and oral interfaces, to provide ventilatory assistance up to 24 h per day, even in patients with unmeasurable vital capacities. (12) Since inflation pressures similar to those delivered through a tracheostomy would be needed to provide equivalent ventilation, the same pressure-related airway changes could develop in individuals receiving NIPPV. Pathologic confirmation of such changes in patients receiving NIPPV is not available, in part because patients have not been using it as long as tracheostomy-assisted ventilation (approximately 15 vs 50 years, respectively). The postmortem examination of the airway in patients who had received NIPPV for many years (comparable in time to those receiving tracheostomy-assisted ventilation) would provide information on this issue.

Of interest, therapy with continuous positive airway pressure has been used to "pneumatically stent" airways in intubated newborns with TBM while awaiting improvement in airway rigidity with growth. (13) It is possible that in our patients the application of tracheostomy-assisted positive-pressure ventilation, while contributing to the TBM, also prevented or delayed airway collapse until the terminal phase of illness.

In addition to the finding of tracheal and bronchial malacia, two of our patients developed erosions that led to hemorrhage, one of which was fatal. Patients with spinal deformities may have tracheostomies that are crooked or eccentric within the tracheal lumen, as demonstrated by a chest radiograph or fiberoptic bronchoscopy. In our experience, fiberoptic bronchoscopy has demonstrated erosions mainly in those patients in whom the tracheostomy tip abuts against the tracheal wall. This situation may be found in patients with scoliosis or in those in whom traction from the ventilator tubing pulls the tracheostomy to one side. Repeated tracheal suctioning to remove secretions also can exacerbate erosions. In at least two of these patients (patients 1 and 5), perforations developed in the trachea that undoubtedly resulted from friction or suction trauma. To avoid this complication, whenever possible, the ventilator tubing should be adjusted so that it does not pull the tracheostomy to one side and the latter is positioned parallel to the axis of the trachea. In wheelchair-dependent individuals, this may require the installation of supports that are designed to keep the tracheostomy in a neutral position. Despite these precautions, however, erosion and perforation may be unavoidable in patients receiving tracheostomy-assisted ventilation for many years. The use of NIPPV should at least prevent tracheal erosions, although, as discussed above, it may not avoid tracheal malacia.

In summary, we have presented autopsy evidence of TBM in five patients with DMD who had received support from uncuffed, tracheostomy-assisted, positive-pressure ventilation for between 5 and 30 years. Histologic findings of the airways revealed variable degrees of cartilage thinning and airway dilatation. Two of the patients also had tracheal perforations, one of which directly led to a massive hemorrhage through a traeheovascular fistula. These clinical and pathologic findings demonstrate that, given enough time, it is possible to develop airway malacia while receiving positive-pressure ventilation, even without the use of tracheostomy cuffs. Thus, these changes may have implications for patients receiving NIPPV, as continuously cycling intratracheal pressures may lead to a similar complication. Such findings would need to be confirmed postmortem in patients who have received long-term NIPPV.

ACKNOWLEDGMENT: The authors thank Theresa Behdjet for the preparation of this manuscript.

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* From the Division of Pulmonary and Critical Care (Dr. Baydur), the Department of Medicine, and the Department of Pathology (Dr. Kanel), Rancho Los Amigos National Rehabilitation Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.

Manuscript received April 30, 2002; revision accepted August 26, 2002.

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

Correspondence to: Ahmet Baydur, MD, FCCP, 2025 Zonal Ave, GNH 1900, Los Angeles, CA, 90033

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