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Ann Thorac Surg 2001;71:989-993
© 2001 The Society of Thoracic Surgeons
a Transplant Unit, Papworth Hospital, Cambridge, United Kingdom
b Department of Radiology, Papworth Hospital, Cambridge, United Kingdom
Accepted for publication May 31, 2000.
Address reprint requests to Dr McNeil, Papworth Hospital, Papworth Everard, Cambridge, CB3 8RE, UK
e-mail: keith.mcneil{at}papworth-tr.anglox.nhs.uk
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Abstract |
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Methods. Data from 123 lung (99 single, 24 bilateral) transplants were reviewed. Potential risk factors for airway complications were analyzed. Stenoses were treated with expanding metal (Gianturco) stents.
Results. Mean follow-up was 749 days. Thirty-five complications developed in 28 recipients (complication rate: 23.8%/anastomosis). Mean time to diagnosis was 47 days. Only Aspergillus infection and airway necrosis were significantly associated with development of complications (p < 0.00001 and p < 0.03, respectively). Stenosis was diagnosed an average of 42 days posttransplant. Average decline in forced expiratory volume in 1 second (FEV1) was 39%. Eighteen patients (13 single and 5 bilateral) required stent insertion. Mean increase in FEV1 poststenting was 87%. Two stent patients died from infectious complications. Six patients required further intervention. Long-term survival and FEV1 did not differ from nonstented patients.
Conclusions. Aspergillus and airway necrosis are associated with the development of airway complications. Expanding metal stents are an effective long-term treatment.
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Introduction |
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TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
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Material and methods |
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TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
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Operative management
Donor organ procurement and lung preservation that we performed were as previously reported. Our own blood-based lung preservation ("Papworth") solution was used for our retrievals [2]. Retrieval teams from other hospitals used crystalloid-based preservation solutions.
Implantation was achieved using the shortest length of donor bronchus possible. Bronchial anastomoses were completed with continuous nonabsorbable (Prolene) sutures in most cases. In 10 early cases (nine SLT and one BLT), interrupted absorbable (Vicryl) sutures were used. In a few cases, a telescoped anastomosis (intentionally or spontaneously) was performed. Cardiopulmonary bypass was employed as dictated by operative and anesthetic requirements.
Postoperative care
All patients received standard cyclosporin-based triple immunosuppression with rabbit antithymocyte globulin induction therapy for 3 days. Antibiotic therapy to cover Staphylococcus aureus and gram-negative organisms was commenced on induction of anesthesia and continued for a minimum of 48 hours, or as dictated by ongoing microbiological surveillance and clinical progress. In 1994, a policy of using nebulized amphotericin B (5 mg three times a day), continued until hospital discharge, was instituted for all patients with a bronchial anastomosis. All patients received co-trimoxazole prophylaxis against pneumocystis infection. Ganciclovir prophylaxis (either intravenous, oral, or both) was given to any patients with positive cytomegalovirus serology (either donor or recipient).
Risk factors
Potential risk factors for the development of airway complications are summarized in Table 1.
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The donor lung preservation method was analyzed in two groups by comparing our protocol with all other techniques. The incidences of bronchial complications in the bilateral lung group and right single lung group were assessed. The bronchial anastomotic technique was classified as a continuous or noncontinuous suture, with or without a telescoped anastomosis when reported.
Potential indicators of impaired tissue perfusion within the first 24 hours (with a consequent increased risk of bronchial ischemia) were assessed. Mechanical ventilation effects were assessed via intubation time and peak airway pressure.
Episodes of rejection in the first 30 postoperative days were diagnosed on standard clinical or histopathological data. Episodes of infection in this period were diagnosed if there was either substantive clinical evidence with or without isolation of a pathogenic organism from lower respiratory tract secretions, or if there was clear histological evidence of infection.
To evaluate the effect of improvements in the surgical and medical management of lung transplant patients, separate analyses were performed on patients transplanted before and after May 1994.
Diagnosis and treatment of airway complications
Bronchoscopy was performed between 10 and 14 days after transplantation, and airway healing graded according to the classification of Couraud and associates [3] with some modifications (Table 2). This modification was undertaken to simplify the description of healing. This grading system was applied retrospectively to evaluate its usefulness in predicting which airways were at risk of developing a complication. The definition of these complications (Table 3) is based on either the appearance of the airway at either bronchoscopy or postmortem examination.
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Statistical analysis
Parametric data are expressed as mean ± standard deviation, and compared using the t test for independent samples. Nonparametric data are expressed as median and range between the 25th and 75th percentiles, and are compared using Wilcoxon’s ranking test for unpaired data (Mann-Whitney U test). Categorical variables are expressed as percentages and compared using 
2 analysis. Actuarial survival curves were constructed using the Kaplan Meier method and compared using the log-rank test. A p value less than 0.05 was considered significant.
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Results |
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The incidence of the different complications is shown in Table 3. Two of the 9 patients in class 1 required treatment by dilatation and endobronchial resection of granulation tissue, respectively. All patients in class 2 received Gianturco expanding metal stents. Two patients died as a result of their airway problems subsequent to stenting, and were considered to have both class 2 and 4 complications simultaneously.
Five patients had airway complication-related deaths on postoperative days 14, 23, 37, 76, and 109, respectively. The first had a cardiac arrest from hypoxemia secondary to bronchial occlusion by mucosal slough. The second and fifth patients died of respiratory failure from infection complicating the airway stenosis despite stenting (see Stent Details below). The third and fourth patients died of massive hemoptysis. Postmortem examination in both cases showed pulmonary artery invasion by Aspergillus. Both patients had initial bronchial necrosis and a partial stenosis not severe enough to require stent insertion.
Risk factor analysis
Eight patients (7 SLT and 1 BLT) were excluded from this analysis because they died in the first postoperative week. At postmortem examination, no airway complications were demonstrated in this group. The remaining 138 anastomoses were considered at risk of developing complications, and they were analyzed for potential risk factors. Results are shown in Table 1.
There were no statistically significant risk factors identified among the recipient and donor factors evaluated. Forty-five anastomoses were performed in recipients receiving immediate preoperative prednisolone treatment, with a mean dose of 12 mg/day per patient, but this was not associated with an increased incidence of airway complications.
Analysis of operative technical factors did not show any statistically significant differences. The use of cardiopulmonary bypass was more frequent in the group without airway complications, with a difference close to significance (49% vs 31%, p = 0.07).
The postoperative factors analyzed were chosen to reflect tissue perfusion, and thus were potentially involved in airway healing. Analysis of these parameters again failed to demonstrate any significant risk for the subsequent development of airway problems.
The incidence of rejection was the same in the two groups. In the first 30 postoperative days, there was no significant difference in the incidence of bacterial infection between the groups. However, there was a very strong relationship between the isolation of Aspergillus fumigatus during this period and the subsequent development of bronchial complications (53% in the complication group vs 14% in the no complication group, p = 0.00001).
The first bronchoscopy was performed 17 days (4 to 59 days) posttransplant. One hundred twenty-four of the 147 anastomoses were classified retrospectively into a healing grade. The incidence of these healing grades and subsequent rates of complications are summarized in Table 4. Because of the small size of the groups, healing grades 2, 3, and 4 were considered together, having in common mucosal or bronchial wall necrosis. There was a significant difference in the incidence of complications between the group with no slough or necrosis (grade 1) and the group with necrosis of some degree (grades 2, 3, and 4). The complication rates were 46% and 63%, respectively (p = 0.03). The interaction between Aspergillus infection and any necrosis (grade 2, 3, or 4) at the first bronchoscopy was analyzed by logistic regression, and this demonstrated both to be independent risk factors for the development of an airway complication. Analysis of the incidence of complications occurring before and after May 1994 showed a significant reduction in airway problems in the later period.
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Pathogenic microorganisms were present at the time of diagnosis in 12 patients. A fumigatus was the most frequently isolated organism. Stent insertion was performed 76 days (23 to 244 days) after transplantation. Only one patient had an additional procedure before stent insertion (resection of granulation tissue). Twenty-six stents were placed at the initial procedure. Half of these needed to be "double" length (50 mm) because of the length of the narrowed section. Fifteen were inserted on the right side but there was no statistical difference in the requirements for stenting between right and left sides. Only 1 patient developed a remarkable complication during stent insertion, this being severe airway hemorrhage requiring short-term ventilatory support.
Outcome
The outcome of stented patients was compared with nonstented patients. There was no significant difference in survival or lung function between the groups. Patients requiring stents suffered more episodes of infection in the first 3 and 6 months posttransplant (p < 0.002 and p < 0.01, respectively). The later incidences of infection, however, were the same in both groups.
Dynamic lung function was assessable in most of the stented patients. The increase in the forced expiratory volume in 1 second (FEV1) measured in the first week after stent insertion was 87% (50% to 290%). The best FEV1 was reached 118 days (4 to 376 days) after stent insertion, with the final increase achieved being 123% (6% to 315%).
Two patients died after stent insertion. The first was an SLT recipient with a grade 4 anastomosis (extensive necrosis) complicated by A fumigatus infection. Stent insertion was performed on day 23 posttransplant because of bronchial collapse. The patient died of respiratory failure on the same day. The second patient received a BLT and presented on day 10 posttransplant with Pseudomonas aeruginosa pneumonia complicating an airway stenosis. Stenting resulted in an immediate improvement of 62% in the FEV1, but progression of the pneumonia was fatal.
Six patients developed a further stenosis after insertion of the first stent(s): 3 interstent, 2 distal to original stent, and 1 in a different airway. In the majority of cases, the problem was fibrotic narrowing. Treatment of these patients was by additional stenting in 4 patients and dilatation in 2. The additional procedures were performed 340 days (18 to 1,267 days) after the original procedure. Two patients developed florid granulation tissue reactions, possibly in response to the stents themselves. This was treated with repeated diathermy resection, or dilatation. There were three late deaths in this group unrelated to their airway complications.
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Comment |
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TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
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It is generally assumed that bronchial ischemia is the main cause of airway complications. Our identification of mucosal or bronchial wall necrosis as an independent risk factor certainly supports this assumption, confirming the findings of previous studies [3]. In the immediate postoperative period, blood supply to the donor bronchus is dependent on low-pressure retrograde perfusion via the pulmonary arteries to the bronchial circulation [8]. In contrast, in heart lung transplantation, the tracheal anastomosis is not ischemic, as there is an established collateral blood supply from the coronary arteries. This explains the very low incidence of anastomotic healing problems (and therefore complications) seen after this procedure.
We have shown a strong correlation between the presence of Aspergillus and the subsequent occurrence of airway complications. Whether Aspergillus infection is present as a consequence of ischemic necrosis, or whether it causes necrosis in its own right, is difficult to know, as there is a frequent coincidence of both factors. However, when bronchial necrosis was described at the first postoperative bronchoscopy together with Aspergillus infection, the incidence of later airway complications was higher than if there was necrosis alone. It is therefore likely that Aspergillus plays a direct role in the development of airway complications.
The practical consequences of these observations are that the aggressive and early treatment of Aspergillus infection, or the use of prophylaxis to reduce the incidence of these infections, may lead to a reduction in the incidence of airway complications. Indeed, the use of nebulized amphotericin B prophylaxis since May 1994 may have accounted for some of the reduction in the incidence of airway complications seen in the latter half of our series.
Among the methods used to treat airway stenoses, placement of stents has gained popularity. Silicone stents have the disadvantage of a narrow lumen, interference with the clearance of airway secretions, and a tendency to dislodge. Expanding metal stents are used increasingly for both benign and malignant stenoses. They are less bulky than silicone stents, exert a greater radial force, are less likely to dislodge, and allow better clearance of secretions [9,10]. Gianturco stent fracture and dislodgement have been reported, although no such events occurred in our series. The good long-term outcome of most of the patients in our series treated with these stents justifies their continued use. Newer wire mesh stents are now available but their long-term efficacy in lung transplant patients is not yet established.
Conclusions
Airway complications continue to be a major problem in SLT and BLT. The early bronchoscopic findings can identify those airways at risk. Identification of Aspergillus will allow timely intervention, which should reduce both the incidence and severity of subsequent airway complications. Management of established stenoses with expanding metal stents has provided good long-term results in terms of both function and survival.
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