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Airway complications after pulmonary transplantation
Airwav Comdications After Pulmonary Transplantation J
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Ian W. Colquhoun, FRCS, Alistair D. Gascoigne, MRCP, John Au, FRCS, Paul A. Corris, FRCP, Colin J. Hilton, FRCS, and John H. Dark, FRCS Cardio-pulmonary Transplant Unit, Freeman Hospital, Newcastle-upon-Tyne, United lngdom
Airway healing was identified initially as one of the fundamental limitations of pulmonary transplantation. Recent experience suggests that this is no longer the case. A series of 67 pulmonary transplants (27 heart-lung, 31 single-lung, 9 double-lung) in 66 patients surviving more than 14 days was reviewed with reference to airway complications. There were 75 anastomoses at risk in two groups as defined by anastomotic location: 47 anastomoses in 38 patients in a bronchial group and 28 anastomoses in 28 patients in a tracheal group. A total of 10 airway complications developed (stenosis in 5 patients [4 bronchial group, 1 tracheal group] and dehiscence in 5 pa-
tients [l bronchial group, 4 tracheal group]) causing two airway-related deaths (2 of 67) in the series. However, no significant correlation could be identified with either ischemic interval, suture technique, type of wrap, preoperative or postoperative steroid therapy, or date of first rejection episode. Airway complications are no longer a major limitation of pulmonary transplantation. Satisfactory airway healing can occur in both the presence of steroid therapy and the absence of an omental or pericardial wrap.
F
technique leaving the donor esophagus in situ was used throughout, and the organs were separated if necessary by appropriate bench dissection. Care was taken to preserve the peritracheal and peribronchial adventitae, and the airway anastomosis was performed two cartilaginous rings proximal to the carina or upper lobe orifice as appropriate. All patients received a similar immunosuppressive regimen with preoperative cyclosporin A (Sandimmun; Sandoz Ltd, Basle, Switzerland) (2 to 8 mg/kg orally according to renal function) and azathioprine (Imuran; Calmic Medical Div, Cheshire, UK) (4 mg/kg). Postoperatively three doses of methylprednisolone (125 mg) were given in the first 24 hours. Cyclosporin A administration was started (0.5 to 2 mg/kg by 6 hourly infusions twice a day, according to renal function) on the first day in association with azathioprine (2 mg . kg-' . day-'). In addition antithymocyte globulin (Lymphoglobuline (equine)antihuman lymphocyte immune globulin; Pasteur Merieux, Lyon, France) was used as a 7-day induction regimen. Episodes of acute rejection, determined by clinical criteria and transbronchial lung biopsy in the absence of a positive bronchoalveolar lavage culture, were treated with pulsed methylprednisolone (10 mg . kg-' . day-') followed by a decreasing oral prednisolone regimen (1mg ' kg-' . day-' lowered to 0.2 mg . kg-' . day-'). Data were collected retrospectively on all patients surviving more than 14 postoperative days. Therefore, 11 patients were excluded from the total group but no airway complication, either on bronchoscopy or at postmortem examination, was demonstrated in this group. On the basis of the structural vascular supply, patients were separated into one of two groups: (1) the tracheal
rom the earliest days of successful clinical pulmonary transplantation, airway-related complications were identified as one of the major limits of the technique. Undoubtedly, improvements in patient selection, surgical ability, and applied techniques, such as bronchial omentopexy, have allowed many successful clinical programs to be established. However, as the frequency of airway complications declines, we must now reassess the current position. With this basic concept in mind we reviewed the results of our pulmonary transplantation program from June 1987 until April 1992. With increasing experience, our management protocols and techniques have evolved and we now attempt to define an overview of our current strategy.
Patients and Methods From the beginning of the pulmonary transplantation program in June 1987 until April 1992, 77 pulmonary transplants were completed at our center. This includes 38 single-lung grafts (SLT), 29 combined heart-lung grafts (HLT), and 10 double-lung transplants (DLT) of which one was an en bloc technique and the other nine were sequential single grafts (SSLT) with bilateral bronchial anastomoses. Distant procurement of the lungs occurred in all cases. Modified Euro-Collins solution, with both methylprednisolone (Solumedrone; Upjohn Ltd, West Sussex, UK) and prostaglandin donor pretreatment was used in all but two cases. A standardized heart-lung block retrieval Accepted for publication Feb 23, 1993. Address reprint requests to Mr Colquhoun, Cardiothoracic Surgery, Western Infirmary, Dumbarton Rd, Glasgow, United Kingdom.
0 1994 by The Society of Thoracic Surgeons
(Ann Thorac Surg 1994;57:141-5)
0003-4975/94/$7.00
142
COLQUHOUN ET AL AIRWAY COMPLICATIONS AFTER TRANSPLANTATION
Ann Thorac Surg 1994;57: 141-5
Table 1. Patient Characteristics Variable No. of transplants No. of patients M/F ratio Age range (Y) Mean age (y)
Diagnosis Eisenmenger's syndrome Primary pulmonary hypertension Bronchiectasis Emphysema (a1antitrypsin deficiency) Cystic fibrosis Obliterative bronchiolitis Idiopathic pulmonary fibrosis Emphysema Histiocytosis X
Tracheal Bronchial Group Group 28 28 10/18
1243 30.4 9 8 4 3 2 2
... ... ...
39 38 21/17 22-59 42.7
...
... 3
... 5 3 14 10 3
group (TG), where a supracarinal tracheal anastomosis was present (including all HLT and 1 patient after DLT); and (2) the bronchial group (BG), including all patients with either SLT or SSLT. Particular attention was paid to the following clinical parameters: ischemic time, suture technique, type of wrap, steroid therapy, and date of first rejection episode. Further details of the patient cohort are provided in Table 1.
Statistics All data were collected retrospectively. Summary statistics were produced on a microcomputer with statistical software (Statgraphics v 2.6, Statistical Graphics Corporation, 1987, Plus*Ware Products, STSC). Paired data were compared with either a x2 or Fisher's exact test, and nonparametric data were compared using the Wilcoxon rank test.
Fig 1 . Computed tomographic scan of the chest after heart-lung transplantation showing left main bronchial stenosis.
strictures in the 47 anastomoses at risk in the BG (incidence, 8.5%). No statistically significant difference was identified between the two respective groups ( p = 0.39, Fisher's exact test). Only one stricture after SLT was truly anastomotic in origin. All others were distal to the anastomosis but proximal to the segmental bronchi (Fig 1). Initially, each case responded to bouginage but 1 patient in the TG subsequently required ne0dymium:yttriumaluminum garnet laser debridement. Three stenoses in the BG alone have required the placement of endobronchial stents for airway patency, representing a stent rate for the series of 4%. A silicone elastomer stent successfully controlled a distal main bronchial stenosis for 4 years but has recently required the insertion of an expandable
Results The overall 30-day mortality for pulmonary transplantation at our center is 23.6%(18/76 patients). However, only two deaths (2.6%)were directly attributable to an airway complication. Both of these represented partial tracheal dehiscence with subsequent mediastinitis after HLT. The average length of follow-up in this series was 62.5 weeks (median, 36 weeks; range, 2 weeks to >4 years). Ten airway complications developed in 10 patients. These comprised five airway stenoses and five episodes of tracheal dehiscence.
Airway Stenosis Only 6.6% (5/75) of anastomoses at risk developed an airway stenosis. All were identified within 2 months of operation and each lesion had a length of less than 1.5 cm. There was one stenotic complication in the 28 anastomoses in the TG. reuresentinc" an incidence of 3.6%,and four
Fin" 2. Expandable metallic stent in ripht bronchus intermedius.
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in the TG were fashioned with a continuous suture technique. However, in the BG only 42.5% (20/47) were performed with a continuous suture. Anastomoses (57.4%, 27/47) were fashioned with a nontelescoping interrupted technique, and in the last 3 patients (8.6%)an interrupted figure-of-8 suture has been used. In the 10 patients in whom either bronchial stenosis or dehiscence developed, 70% were performed using a continuous suture. However, when the complication rate was compared between the continuous (7/44) and the interrupted techniques (3/31), no significant difference was noted ( p = 0.34, Fisher’s exact test).
Bronchial Wrap
Fig 3. Chest radiogram showing pneumopericardium after complete dehiscence of left bronchial anastomosis.
metallic stent (Cook Inc). This technique was also used to control a stenosis in the right intermediate bronchus after sequential SLT (Fig 2), and we now believe it to be the technique of choice for fibrous airway strictures.
Airway Dehiscence The incidence of dehiscence in the entire series was 6.6% (5/75 anastomoses at risk). Four episodes (14.3%)occurred in the TG. Partial dehiscence developed in 3 of these patients within 30 days of transplantation and caused two airway-related deaths owing to septicemia and multiple organ failure. The remaining case was identified 4 years after transplantation at routine surveillance transbronchial biopsy and required no further action. A complete anastomotic dehiscence developed on the 10th postoperative day in 1 patient in the BG (2.1%, 1/47) (Fig 3). This was successfully resutured and a pericardial wrap used to replace the necrotic omental pedicle [l].Follow-up bronchoscopy over the subsequent 3 years has confirmed satisfactory healing and no evidence of stricture formation.
Ischemic Time When ischemic time was considered, no significant difference was seen ( p = 0.8, Wilcoxon rank test) between the group with stenosis and dehiscence (median, 239.5 minutes; range, 121 to 326 minutes) and the patients with normal airway healing (median, 227.5 minutes; range, 90 to 447 minutes). In particular, there has not been a greater incidence of airway problems in the second bronchial anastomosis after SSLT, despite the necessary increased ischemic interval.
Suture Technique Monofilament 3/0 polypropylene (Prolene; Ethicon, Edinburgh, UK) was used in all cases. All anastomoses (28/28)
A pedicle graft was performed in 3.6% (1/28) of the TG and 68.1% (32/47) of the BG. Omentum was used in the single case after HLT but unfortunately failed to prevent airway dehiscence resulting in one of the airway-related deaths. In the BG, pericardium has been used for 17 cases (53.1%),omentum in 14 (43.7%), and intercostal muscle on one occasion (3.1%). Omentum was used almost exclusively for the first 2 years of the program and was later succeeded by use of a pericardial pedicle graft. After the introduction of this change in our practice, there has been no difference in complication rate (3/14 with omental pedicles compared with 3/17 with pericardial pedicles; p = 0.57). In the last 8 months, simple tissue approximation with no formal wrapping procedure has been carried out. As yet, no airway complications have arisen in the 13 bronchial anastomoses at risk.
Steroid Therapy Five patients (17.8%) in the TG were on preoperative steroids (2 to 30 mg/day of prednisolone) as were 11 patients in the BG (28.9%;3 to 20 mg/day of prednisolone). None of these patients demonstrated evidence of skin thinning or any complication of prolonged steroid ingestion at the time of transplantation. Only 2 patients on preoperative steroids after HLT had development of an airway complication (one stenosis, one dehiscence), and there was no significant difference between the steroid positive and negative groups with relation to airway complications ( p = 0.057, Fisher’s exact test). In keeping with other transplantation programs, postoperative steroids were initially avoided, other than short pulsed courses of methylprednisolone to treat pulmonary rejection. However, with the low incidence of airway problems in our series, we have now adopted a policy of commencing routine steroid administration in the immediate postoperative period. After three bolus doses of 125 mg of methylprednisolone in the first 24-hour period, enteral prednisolone is started at 1 mg/kg and reduced to 0.2 mg/kg during the next 10 days, depending on rejection status. After the routine introduction of steroids within the first postoperative week, no significant change in the incidence of airway complications has been noted when steroids were started early (4/43) compared with the original late (6/22) regimen ( p = 0.06, Fisher’s exact test).
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COLQUHOUNET AL AIRWAY COMPLICATIONS AFTER TRANSPLANTATION
Fig 4. Right coronary angiogram after heart-lung transplantation demonstrating coronary to bronchial collateral farrow).
Effect of First Rejection Episode Acute rejection is known to alter the mucosal blood flow. Therefore, we studied the effect of timing of the first rejection episode at a period when the airways are most likely to be susceptible to damage. No significant difference ( p = 0.59, Wilcoxon rank test) was noted between the groups with (median, 9 days; range, 4 to 17) or without airway complication (median, 8 days; range, 5 to 29) when analyzed with respect to day of first rejection episode proven histologically on transbronchial lung biopsy.
Comment Historically, airway complications have represented one of the main limiting features of pulmonary transplantation [2-51. The absence of a systemic vascular supply to the organ plays a major role in the initiation of airwayrelated complications [2, 61, placing lung transplantation in a unique category among all solid organ transplants. In the early postoperative period, airway viability is dependent on a vascular supply from the pulmonary circulation [7], retrograde pulmonary artery to bronchial collaterals [8], and coronary to bronchial collateral flow (Fig 4). In addition airway length [9], corticosteroids [lo, 111, and azathioprine [ll] have all been shown to have some additional effect on airway healing. After the initial surgical results, refinement of surgical technique [ll-151 has allowed successful pulmonary transplantation to become established routinely [ 12-16]. Late restoration of the bronchial circulation after transplantation has been confirmed [17], but the majority of problems arise in the immediate postoperative period. Improved airway healing during this ischemic interval has been attempted by indirect revascularization of the airway using omentum [6,18-201, internal mammary artery [20], intercostal artery [20, 211, saphenous vein conduits [22], and pericardium-based pedicles. Every technique has its enthusiast and there is
Ann Thorac Surg
1994;57141-5
currently an increasing interest in restoration of the systemic bronchial artery circulation either by direct reimplantation of a bronchial artery orifice into the aorta or indirectly by using an internal mammary artery graft. As yet, neither method has shown convincing benefit nor gained widespread popularity. Although a long-term effect of direct revascularization on bronchiolitis obliterans has been suggested, it remains as yet unproven. However, we must now reconsider many of the fundamental preconceptions for airway healing such as steroid avoidance and the necessity for an omental pedicle. Although our numbers are small, the results show a remarkably low incidence of anastomotic complications (10/75),both at bronchial and supracarinal level, with only two airway-related deaths in 67 patients at risk. This appears to be unrelated to suture technique, type of indirect revascularization, steroid therapy, or the early effect of rejection. As our experience has progressed, routine omentopexy with the additional sequelae of an abdominal incision was abandoned in favor of a vascularized pericardial wrap. We have now discontinued any routine form of indirect revascularization, without any airway complication in the last 13 patients followed up for up to 8 months. Preoperative steroid therapy was an absolute contraindication to pulmonary transplantation at the start of our series. However, this is no longer the case. We still maintain a policy of steroid avoidance where possible preoperatively, but would accept patients on oral steroid therapy without clinical evidence of severe skin thinning or other cushingoid manifestations. Finally, the introduction of early steroids on the first postoperative day has not altered the frequency of anastomotic dehiscence in our series. The overall actions of steroids in transplantation remain complex. Although exerting catabolic actions delaying wound healing in general, they also decrease rejection episodes that may be associated with early tissue damage and thus may positively influence airway healing. In conclusion, satisfactory airway healing can occur in both the presence of steroids and the absence of an omental or pericardial wrap [23]. Any complication when it occurs does not necessarily result in the death of the patient [24, 251. Aggressive open surgical management of airway dehiscence allows potential survival [l], whereas the use of expandable metallic stents for airway stenosis when the mucosa is healed would seem to be a definite advance [26, 271.
References 1. Kirk AJB, Conacher ID, Corns PA, Ashcroft T, Dark JH. Successful surgical management of bronchial dehiscence after single lung transplantation. Ann Thorac Surg 1990;49: 147-9. 2. Mills NL, Boyd AD, Gheranpong C. The significance of the bronchial circulation in lung transplantation. J Thorac Cardiovasc Surg 1970;60:866-78. 3. Deffebach ME, Charan NB, Lakshminarayan S, Butler J. The bronchial circulation. Am Rev Respir Dis 1987;135:463-81. 4. Wildevuur CRH, Benfield JR. A review of 23 human lung transplantsby 20 surgeons. Ann Thorac Surg 1970;9:489-515.
Ann Thorac Surg 1994;57 141-5
5. Veith FJ. Lung transplantation. Surg Clin North Am 1978;58: 357-64. 6. Lima 0, Goldberg M, Peters WJ, Ayabe H, Townsend E, Cooper JD. Bronchial omentopexy in canine lung transplantation. J Thorac Cardiovasc Surg 1982;83:41%21. 7. Barman SA, Ardell JL, Parker JC, Perry ML, Taylor AE. Pulmonary and systemic blood flow contributions to the upper airways in canine lung. Am J Physiol1988;255:1130-5. 8. Ladowski JS, Hardesty RL, Griffith BP. The pulmonary artery blood supply to the supracarinal trachea. Heart Transplant 1984;4:40-2. 9. Pinsker KL, Koerner SK, Kamholz SL, Hagstrom JWC, Veith FJ. Effect of donor bronchial length on healing. J Thorac Cardiovasc Surg 1979;77669-73. 10. Pinkser KL, Veith FJ, Kamholz SL, Montefusco C, Emson E, Hagstrom JWC. Influence of bronchial circulation and corticosteroid therapy on bronchial anastomotic healing. J Thorac Cardiovasc Surg 1984;87439--24. 11. Lima 0, Cooper JD, Peters WJ, et al. Effects of methylprednisolone and azathioprine on bronchial healing following lung autotransplantation. J Thorac Cardiovasc Surg 1981;82: 211-5. 12. Griffith BP, Hardesty RL, Trento A, et al. Heart lung transplantation: lessons learned and future hopes. Ann Thorac Surg 1987;43:6-16. 13. Cooper JD, Pearson FG, Patterson GA, et al. Technique of successful lung transplantation in humans. J Thorac Cardiovasc Surg 1987;93:172-81. 14. Raju S, Heath BJ, Warren ET, Hardy JD. Single- and doublelung transplantation. Problems and possible solutions. Ann Surg 1990;211:681-93. 15. Vouhe PR, Dartevelle PG. Heart-lung transplantation. J Thorac Cardiovasc Surg 1989;97:90&10. 16. Noiclerc MJ, Metras D, Vaillant A, et al. Bilateral bronchial anastomosis in double lung and heart-lung transplantations. Eur J Cardiothorac Surg 1990;4:314-7.
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17. Sieglman SS,'Hagstrom JWC, Koerner SK, Veith FJ. Restoration of bronchial artery circulation after canine lung allotransplantation. J Thorac Cardiovasc Surg 1977;5:7925. 18. Morgan E, Lima 0, Goldberg M, Ajabe H, Ferdman A, Cooper JD. Improved bronchial healing in canine left lung reimplantation using omental pedicle wrap. J Thorac Cardiovasc Surg 1983;85:134-9. 19. Shirakusa T, Motonaga R. Lung allografts with and without omentopexy in canines-bronchofiberscopic and histologic observation of bronchial anastomosis healing. Jpn J Surg 1989;19(2):246-50. 20. Turrentine MW, Kesler KA, Wright CD, et al. Effect of omental, intercostal, and internal mammary artery pedicle wraps on bronchial healing. Ann Thorac Surg 1990;49:574-9. 21. Fell SC, Mollenkopf FP, Montefusco CM, et al. Revascularization of ischemic bronchial anastomoses by an intercostal pedicle flap. J Thorac Cardiovasc Surg 1985;90:172-8. 22. Courand L, Baudet E, Martigne C, et al. Bronchial revascularization in double-lung transplantation in a series of 8 patients. Ann Thor Surg 1992;53:8%94. 23. Auteri JS, Jeevanandan V, Sanchez JA, Marboe CC, Kirby TJ, Smith CR. Normal bronchial healing without bronchial wrapping in canine lung transplantation. Ann Thor Surg 1992;53: 8M. 24. Schafers H-J, Haydock DA, Cooper JD. The prevalence and management of bronchial anastomotic complications in lung transplantation. J Thorac Cardiovasc Surg 1991;101:1044-52. 25. Cooper JD, Pearson FG, Patterson GA. Use of silicone stents in the management of airway problems. Ann Thorac Surg 1989;47371-8. 26. Simonds AK, Irving JD, Clarke SW, Dick R. Use of expandable metal stents in the treatment of bronchial obstruction. Thorax 1989;44:680-1. 27. Wallace MJ, Chamsangavej C, Ogawa K, et al. Tracheobronchial tree expandable metallic stents used in experimental and clinical applications. Radiology 1986;158:309-12.
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Ian W. Colquhoun, FRCS, Alistair D. Gascoigne, MRCP, John Au, FRCS, Paul A. Corris, FRCP, Colin J. Hilton, FRCS, and John H. Dark, FRCS Cardio-pulmonary Transplant Unit, Freeman Hospital, Newcastle-upon-Tyne, United lngdom
Airway healing was identified initially as one of the fundamental limitations of pulmonary transplantation. Recent experience suggests that this is no longer the case. A series of 67 pulmonary transplants (27 heart-lung, 31 single-lung, 9 double-lung) in 66 patients surviving more than 14 days was reviewed with reference to airway complications. There were 75 anastomoses at risk in two groups as defined by anastomotic location: 47 anastomoses in 38 patients in a bronchial group and 28 anastomoses in 28 patients in a tracheal group. A total of 10 airway complications developed (stenosis in 5 patients [4 bronchial group, 1 tracheal group] and dehiscence in 5 pa-
tients [l bronchial group, 4 tracheal group]) causing two airway-related deaths (2 of 67) in the series. However, no significant correlation could be identified with either ischemic interval, suture technique, type of wrap, preoperative or postoperative steroid therapy, or date of first rejection episode. Airway complications are no longer a major limitation of pulmonary transplantation. Satisfactory airway healing can occur in both the presence of steroid therapy and the absence of an omental or pericardial wrap.
F
technique leaving the donor esophagus in situ was used throughout, and the organs were separated if necessary by appropriate bench dissection. Care was taken to preserve the peritracheal and peribronchial adventitae, and the airway anastomosis was performed two cartilaginous rings proximal to the carina or upper lobe orifice as appropriate. All patients received a similar immunosuppressive regimen with preoperative cyclosporin A (Sandimmun; Sandoz Ltd, Basle, Switzerland) (2 to 8 mg/kg orally according to renal function) and azathioprine (Imuran; Calmic Medical Div, Cheshire, UK) (4 mg/kg). Postoperatively three doses of methylprednisolone (125 mg) were given in the first 24 hours. Cyclosporin A administration was started (0.5 to 2 mg/kg by 6 hourly infusions twice a day, according to renal function) on the first day in association with azathioprine (2 mg . kg-' . day-'). In addition antithymocyte globulin (Lymphoglobuline (equine)antihuman lymphocyte immune globulin; Pasteur Merieux, Lyon, France) was used as a 7-day induction regimen. Episodes of acute rejection, determined by clinical criteria and transbronchial lung biopsy in the absence of a positive bronchoalveolar lavage culture, were treated with pulsed methylprednisolone (10 mg . kg-' . day-') followed by a decreasing oral prednisolone regimen (1mg ' kg-' . day-' lowered to 0.2 mg . kg-' . day-'). Data were collected retrospectively on all patients surviving more than 14 postoperative days. Therefore, 11 patients were excluded from the total group but no airway complication, either on bronchoscopy or at postmortem examination, was demonstrated in this group. On the basis of the structural vascular supply, patients were separated into one of two groups: (1) the tracheal
rom the earliest days of successful clinical pulmonary transplantation, airway-related complications were identified as one of the major limits of the technique. Undoubtedly, improvements in patient selection, surgical ability, and applied techniques, such as bronchial omentopexy, have allowed many successful clinical programs to be established. However, as the frequency of airway complications declines, we must now reassess the current position. With this basic concept in mind we reviewed the results of our pulmonary transplantation program from June 1987 until April 1992. With increasing experience, our management protocols and techniques have evolved and we now attempt to define an overview of our current strategy.
Patients and Methods From the beginning of the pulmonary transplantation program in June 1987 until April 1992, 77 pulmonary transplants were completed at our center. This includes 38 single-lung grafts (SLT), 29 combined heart-lung grafts (HLT), and 10 double-lung transplants (DLT) of which one was an en bloc technique and the other nine were sequential single grafts (SSLT) with bilateral bronchial anastomoses. Distant procurement of the lungs occurred in all cases. Modified Euro-Collins solution, with both methylprednisolone (Solumedrone; Upjohn Ltd, West Sussex, UK) and prostaglandin donor pretreatment was used in all but two cases. A standardized heart-lung block retrieval Accepted for publication Feb 23, 1993. Address reprint requests to Mr Colquhoun, Cardiothoracic Surgery, Western Infirmary, Dumbarton Rd, Glasgow, United Kingdom.
0 1994 by The Society of Thoracic Surgeons
(Ann Thorac Surg 1994;57:141-5)
0003-4975/94/$7.00
142
COLQUHOUN ET AL AIRWAY COMPLICATIONS AFTER TRANSPLANTATION
Ann Thorac Surg 1994;57: 141-5
Table 1. Patient Characteristics Variable No. of transplants No. of patients M/F ratio Age range (Y) Mean age (y)
Diagnosis Eisenmenger's syndrome Primary pulmonary hypertension Bronchiectasis Emphysema (a1antitrypsin deficiency) Cystic fibrosis Obliterative bronchiolitis Idiopathic pulmonary fibrosis Emphysema Histiocytosis X
Tracheal Bronchial Group Group 28 28 10/18
1243 30.4 9 8 4 3 2 2
... ... ...
39 38 21/17 22-59 42.7
...
... 3
... 5 3 14 10 3
group (TG), where a supracarinal tracheal anastomosis was present (including all HLT and 1 patient after DLT); and (2) the bronchial group (BG), including all patients with either SLT or SSLT. Particular attention was paid to the following clinical parameters: ischemic time, suture technique, type of wrap, steroid therapy, and date of first rejection episode. Further details of the patient cohort are provided in Table 1.
Statistics All data were collected retrospectively. Summary statistics were produced on a microcomputer with statistical software (Statgraphics v 2.6, Statistical Graphics Corporation, 1987, Plus*Ware Products, STSC). Paired data were compared with either a x2 or Fisher's exact test, and nonparametric data were compared using the Wilcoxon rank test.
Fig 1 . Computed tomographic scan of the chest after heart-lung transplantation showing left main bronchial stenosis.
strictures in the 47 anastomoses at risk in the BG (incidence, 8.5%). No statistically significant difference was identified between the two respective groups ( p = 0.39, Fisher's exact test). Only one stricture after SLT was truly anastomotic in origin. All others were distal to the anastomosis but proximal to the segmental bronchi (Fig 1). Initially, each case responded to bouginage but 1 patient in the TG subsequently required ne0dymium:yttriumaluminum garnet laser debridement. Three stenoses in the BG alone have required the placement of endobronchial stents for airway patency, representing a stent rate for the series of 4%. A silicone elastomer stent successfully controlled a distal main bronchial stenosis for 4 years but has recently required the insertion of an expandable
Results The overall 30-day mortality for pulmonary transplantation at our center is 23.6%(18/76 patients). However, only two deaths (2.6%)were directly attributable to an airway complication. Both of these represented partial tracheal dehiscence with subsequent mediastinitis after HLT. The average length of follow-up in this series was 62.5 weeks (median, 36 weeks; range, 2 weeks to >4 years). Ten airway complications developed in 10 patients. These comprised five airway stenoses and five episodes of tracheal dehiscence.
Airway Stenosis Only 6.6% (5/75) of anastomoses at risk developed an airway stenosis. All were identified within 2 months of operation and each lesion had a length of less than 1.5 cm. There was one stenotic complication in the 28 anastomoses in the TG. reuresentinc" an incidence of 3.6%,and four
Fin" 2. Expandable metallic stent in ripht bronchus intermedius.
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in the TG were fashioned with a continuous suture technique. However, in the BG only 42.5% (20/47) were performed with a continuous suture. Anastomoses (57.4%, 27/47) were fashioned with a nontelescoping interrupted technique, and in the last 3 patients (8.6%)an interrupted figure-of-8 suture has been used. In the 10 patients in whom either bronchial stenosis or dehiscence developed, 70% were performed using a continuous suture. However, when the complication rate was compared between the continuous (7/44) and the interrupted techniques (3/31), no significant difference was noted ( p = 0.34, Fisher’s exact test).
Bronchial Wrap
Fig 3. Chest radiogram showing pneumopericardium after complete dehiscence of left bronchial anastomosis.
metallic stent (Cook Inc). This technique was also used to control a stenosis in the right intermediate bronchus after sequential SLT (Fig 2), and we now believe it to be the technique of choice for fibrous airway strictures.
Airway Dehiscence The incidence of dehiscence in the entire series was 6.6% (5/75 anastomoses at risk). Four episodes (14.3%)occurred in the TG. Partial dehiscence developed in 3 of these patients within 30 days of transplantation and caused two airway-related deaths owing to septicemia and multiple organ failure. The remaining case was identified 4 years after transplantation at routine surveillance transbronchial biopsy and required no further action. A complete anastomotic dehiscence developed on the 10th postoperative day in 1 patient in the BG (2.1%, 1/47) (Fig 3). This was successfully resutured and a pericardial wrap used to replace the necrotic omental pedicle [l].Follow-up bronchoscopy over the subsequent 3 years has confirmed satisfactory healing and no evidence of stricture formation.
Ischemic Time When ischemic time was considered, no significant difference was seen ( p = 0.8, Wilcoxon rank test) between the group with stenosis and dehiscence (median, 239.5 minutes; range, 121 to 326 minutes) and the patients with normal airway healing (median, 227.5 minutes; range, 90 to 447 minutes). In particular, there has not been a greater incidence of airway problems in the second bronchial anastomosis after SSLT, despite the necessary increased ischemic interval.
Suture Technique Monofilament 3/0 polypropylene (Prolene; Ethicon, Edinburgh, UK) was used in all cases. All anastomoses (28/28)
A pedicle graft was performed in 3.6% (1/28) of the TG and 68.1% (32/47) of the BG. Omentum was used in the single case after HLT but unfortunately failed to prevent airway dehiscence resulting in one of the airway-related deaths. In the BG, pericardium has been used for 17 cases (53.1%),omentum in 14 (43.7%), and intercostal muscle on one occasion (3.1%). Omentum was used almost exclusively for the first 2 years of the program and was later succeeded by use of a pericardial pedicle graft. After the introduction of this change in our practice, there has been no difference in complication rate (3/14 with omental pedicles compared with 3/17 with pericardial pedicles; p = 0.57). In the last 8 months, simple tissue approximation with no formal wrapping procedure has been carried out. As yet, no airway complications have arisen in the 13 bronchial anastomoses at risk.
Steroid Therapy Five patients (17.8%) in the TG were on preoperative steroids (2 to 30 mg/day of prednisolone) as were 11 patients in the BG (28.9%;3 to 20 mg/day of prednisolone). None of these patients demonstrated evidence of skin thinning or any complication of prolonged steroid ingestion at the time of transplantation. Only 2 patients on preoperative steroids after HLT had development of an airway complication (one stenosis, one dehiscence), and there was no significant difference between the steroid positive and negative groups with relation to airway complications ( p = 0.057, Fisher’s exact test). In keeping with other transplantation programs, postoperative steroids were initially avoided, other than short pulsed courses of methylprednisolone to treat pulmonary rejection. However, with the low incidence of airway problems in our series, we have now adopted a policy of commencing routine steroid administration in the immediate postoperative period. After three bolus doses of 125 mg of methylprednisolone in the first 24-hour period, enteral prednisolone is started at 1 mg/kg and reduced to 0.2 mg/kg during the next 10 days, depending on rejection status. After the routine introduction of steroids within the first postoperative week, no significant change in the incidence of airway complications has been noted when steroids were started early (4/43) compared with the original late (6/22) regimen ( p = 0.06, Fisher’s exact test).
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Fig 4. Right coronary angiogram after heart-lung transplantation demonstrating coronary to bronchial collateral farrow).
Effect of First Rejection Episode Acute rejection is known to alter the mucosal blood flow. Therefore, we studied the effect of timing of the first rejection episode at a period when the airways are most likely to be susceptible to damage. No significant difference ( p = 0.59, Wilcoxon rank test) was noted between the groups with (median, 9 days; range, 4 to 17) or without airway complication (median, 8 days; range, 5 to 29) when analyzed with respect to day of first rejection episode proven histologically on transbronchial lung biopsy.
Comment Historically, airway complications have represented one of the main limiting features of pulmonary transplantation [2-51. The absence of a systemic vascular supply to the organ plays a major role in the initiation of airwayrelated complications [2, 61, placing lung transplantation in a unique category among all solid organ transplants. In the early postoperative period, airway viability is dependent on a vascular supply from the pulmonary circulation [7], retrograde pulmonary artery to bronchial collaterals [8], and coronary to bronchial collateral flow (Fig 4). In addition airway length [9], corticosteroids [lo, 111, and azathioprine [ll] have all been shown to have some additional effect on airway healing. After the initial surgical results, refinement of surgical technique [ll-151 has allowed successful pulmonary transplantation to become established routinely [ 12-16]. Late restoration of the bronchial circulation after transplantation has been confirmed [17], but the majority of problems arise in the immediate postoperative period. Improved airway healing during this ischemic interval has been attempted by indirect revascularization of the airway using omentum [6,18-201, internal mammary artery [20], intercostal artery [20, 211, saphenous vein conduits [22], and pericardium-based pedicles. Every technique has its enthusiast and there is
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currently an increasing interest in restoration of the systemic bronchial artery circulation either by direct reimplantation of a bronchial artery orifice into the aorta or indirectly by using an internal mammary artery graft. As yet, neither method has shown convincing benefit nor gained widespread popularity. Although a long-term effect of direct revascularization on bronchiolitis obliterans has been suggested, it remains as yet unproven. However, we must now reconsider many of the fundamental preconceptions for airway healing such as steroid avoidance and the necessity for an omental pedicle. Although our numbers are small, the results show a remarkably low incidence of anastomotic complications (10/75),both at bronchial and supracarinal level, with only two airway-related deaths in 67 patients at risk. This appears to be unrelated to suture technique, type of indirect revascularization, steroid therapy, or the early effect of rejection. As our experience has progressed, routine omentopexy with the additional sequelae of an abdominal incision was abandoned in favor of a vascularized pericardial wrap. We have now discontinued any routine form of indirect revascularization, without any airway complication in the last 13 patients followed up for up to 8 months. Preoperative steroid therapy was an absolute contraindication to pulmonary transplantation at the start of our series. However, this is no longer the case. We still maintain a policy of steroid avoidance where possible preoperatively, but would accept patients on oral steroid therapy without clinical evidence of severe skin thinning or other cushingoid manifestations. Finally, the introduction of early steroids on the first postoperative day has not altered the frequency of anastomotic dehiscence in our series. The overall actions of steroids in transplantation remain complex. Although exerting catabolic actions delaying wound healing in general, they also decrease rejection episodes that may be associated with early tissue damage and thus may positively influence airway healing. In conclusion, satisfactory airway healing can occur in both the presence of steroids and the absence of an omental or pericardial wrap [23]. Any complication when it occurs does not necessarily result in the death of the patient [24, 251. Aggressive open surgical management of airway dehiscence allows potential survival [l], whereas the use of expandable metallic stents for airway stenosis when the mucosa is healed would seem to be a definite advance [26, 271.
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