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Lung Transplantation for Patients Older Than 65 Years: Is It a Feasible Option?
Lung Transplantation for Patients Older Than 65 Years: Is It a Feasible Option? T.N. Machuca, S.M. Camargo, S.M. Schio, V. Lobato, L.B. Sanchez, F. Perin, J.C. Felicetti, and J.J. Camargo ABSTRACT Background. Advanced age has been a relative contraindication to lung transplantation. However, the exact age limit for this procedure has not yet been established. The aim of this work is to present our experience with this particular group. Methods. This retrospective review included medical charts of patients who underwent lung transplantation at our institution from January 2004 to February 2009: namely, 112 cadaveric lung transplants with 12 patients (10.7%) ⬎65 years old. Results. There were 9 male patients and the overall mean age was 68 years (range 66 –72). The indications were pulmonary fibrosis in 8 and emphysema in 4 cases. Four patients had mild coronary artery disease and 4 systemic hypertension. All of the procedures were unilateral and only 2 required extracorporeal circulation. Only 5 patients received blood product transfusions intraoperatively; the mean ischemic time was 222 minutes. Four patients developed primary graft dysfunction, the mean requirement for mechanical ventilation was 30 hours, and the mean intensive care unit stay, 11 days. Postoperative complications were respiratory infections (n ⫽ 8), catheter-related infection (n ⫽ 1), atrial fibrillation (n ⫽ 2). The mean hospital stay was 28 days and the 1-year survival was 75%. Conclusion. Lung transplantation is a feasible option for well-selected patients with end-stage pulmonary disease who are ⬎65 years old. Our study reinforces the modern trend for unilateral procedures in this situation. ECAUSE OF enourmous advances in recipient selection, organ preservation, anesthetic management, surgical technique, immediate posttransplant critical care, and long-term follow-up, the results of lung transplantation have improved to encouraging numbers. According to the International Society for Heart and Lung Transplantation (ISHLT) report of 2009, the 1-year patient survival among procedures performed from January 1994 to June 2007 was 79%.1 This favorable scenario has led lung transplant teams to offer the procedure to a larger group of recipients. One group that may benefit from this trend is that of older patients. As a matter of fact, this same report has shown that the mean recipient age, has increased each year to reach its peak in 2008, 50.8 years. In addition, the number of lung transplants has also increased among patients of ⱖ60 years from 15% in 1998 to 35% in 2008. Mainly owing to the scarcity of donors with usable lungs, it is crucial to carefully select subjects likely to have the best
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© 2011 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 43, 233–235 (2011)
benefit from the procedure. Thus, it is accepted that age ⬎65 years is a relative contraindication for lung transplantation.2 However, a few groups have shown favorable lung transplantation results with well-selected patients within this age range.3,4 The aim of this study is to present our experience with this particular population, focusing on recipient selection, early results, and posttransplant complications.
From the Lung Transplantation Group (T.N.M., S.M.C., S.M.S., L.B.S., F.P., J.C.F., J.J.C.), Hospital Dom Vicente Scherer, Santa Casa de Porto Alegre and the Thoracic Surgery Service (T.N.M., S.M.C., V.L., F.P., J.C.F., J.J.C.), Pavilhão Pereira Filho, Santa Casa de Porto Alegre, Porto Alegre, RS, Brazil. Address reprint requests to Tiago Noguchi Machuca, São Francisco da Califórnia street, 222, apto 304, Porto Alegre, Rio Grande do Sul, Brazil, 90550-080. E-mail: machuca36@hotmail. com 0041-1345/–see front matter doi:10.1016/j.transproceed.2010.12.010 233
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This retrospective study included patients who underwent lung transplantation from January 2004 to February 2009. We reviewed recipient preoperative data, intraoperative features, and data regarding postoperative course. In this period, we performed 112 procedures from cadaveric donors, including 12 (10.7%) recipients ⬎65 years old. Patients were eligible for lung transplantation according to ISHLT criteria.5 Organ procurement was based on conventional methods.6 Our immunosuppressive regimen and surgical technique have been described elsewhere.7 Routine pretransplant evaluation included the performance of coronary angiography and pulmonary artery catheterization.
Due to hemothorax, 2 patients required early reintervention; one of these was the patient with previous LVRS. In the first month, 8 patients had acute rejection episodes, which were diagnosed based on clinicoradiologic findings in 4 and on histologic findings in the remaining 4 cases (grade 2 in 3 and grade 3 in 1 subject). There was only 1 in-hospital mortality due to massive hemoptysis in a patient with a bronchoarterial fistula. The 1-year survival was 75%. Three other patients died due to respiratory infections (n ⫽ 2) in addition to the bronchoarterial fistula (n ⫽ 1).
RESULTS
DISCUSSION
There were 9 male patients and the overall mean age was 68 years (range, 66 –72). The indications were pulmonary fibrosis (n ⫽ 8) and emphysema (n ⫽ 4). The nutritional status of all 12 patients was acceptable, with no case of underweight and 5 cases of overweight individuals; the mean body mass index (BMI) was 25.3 kg/m2 (range, 21.5–29.8). The mean distance in the 6-minute walk test was 308 meters (range, 25– 475). All patients were ambulatory. There was no case of preoperative airway colonization. Regarding pulmonary hemodynamics, only 3 patients had a systolic pulmonary artery pressure ⬎40 mm Hg on pretransplant right heart catheterization (mean, 33 mm Hg; range, 21–50). Comorbidities were present in 7 patients, namely, mild coronary artery disease (n ⫽ 3), systemic arterial hypertension (n ⫽ 3), and both conditions (n ⫽ 1). Seven patients were on oral corticosteroids at the time of transplantation, but in all cases the daily dose was ⬍20 mg of prednisone. All patients underwent single lung transplantation, which was left-sided in 9 cases. Owing to pulmonary hypertension, 2 patients required cardiopulmonary bypass. The mean ischemic time was 222 mimutes (range, 110 –300). Two patients experienced intraoperative bleeding ⬎1500 mL; in both cases, it was due to extensive pleural adhesions. In one case an emphysema patient had previous ipsilateral lung volume reduction surgery (LVRS). Tranfusion of red blood cells was required in 5 cases. Primary graft dysfunction was recorded in 4 cases: moderate in 2 and severe in the remaining 2. Eight patients were extubated within the first 12 postoperative hours. The patients with primary graft dysfunction had a mean requirement of mechanical ventilation of 75 hours. Two patients had no requirement for vasopressors in the immediate postoperative period. The remaining 10 patients required vasoactive drugs for a mean of 26.3 hours. Nine patients developed infectious complications in the early posttransplant period. The site was pulmonary in 8 cases: Pseudomonas aeruginosa (n ⫽ 3), Staphylococcus aureus (n ⫽ 1), or Aspergillus fumigatus (n ⫽ 1). In addition, 3 cases underwent empirical treatment due to no microbiological recovery. In 1 case, it was catheter-related due to methicillin-resistant S aureus. Two patients presented with atrial fibrillation, which was successfully reversed in both.
One of the major points in the discussion about lung transplantation for patients ⬎65 years regards the performance of unilateral versus bilateral procedures. Review of the United Network for Organ Sharing (UNOS) database from 1998 to 2004 revealed 1656 patients of ⱖ60 years who underwent lung transplantation.8 The survival of patients with single-sided procedures was not different from patients undergoing bilateral transplantation. In a single-institutional report of 51 recipients aged ⱖ60 years. The early outcomes were similar between patients who underwent either single or bilateral transplantation, with 30-day survivals of 81% versus 92%, respectively.9 However, other reports have shown the deleterious effects of double-lung transplantations in older patients. In an analysis of 18 patients from the Hannover group, not only the periods of mechanical ventilation and ICU stay were longer in patients with bilateral procedures, but also the 1-year survival was strikingly worse (43% vs 73%).10 When the evaluation was stratified according to indication, there was also a trend for improved outcome for single lung transplantation in older patients with chronic obstructive pulmonary disease. In another UNOS registry analysis, patients up to 60 years showed a survival benefit when submitted to bilateral lung transplantation. Above this age, the 1-year survival fell from 93% (for single transplants) to 77.8% (for bilateral procedures).11 In the setting of patients with pulmonary fibrosis, the 1-year survival for bilateral transplantations in patients ⬎59 years old was also worse (47.7% vs 62.9%).12 Supported by these results and by the greater probability of receiving a graft when listed for a unilateral procedure, specially in areas suffering a donor shortage, it has been our policy to perfom single lung transplantation for older patients with either pulmonary fibrosis or emphysema. In addition to procedure selection, careful recipient selection is also crucial for successful lung transplantation in elderly patients. We believe that 1 major point is pulmonary hemodynamics. Among patients with pulmonary fibrosis undergoing single lung transplantation, there is a linear correlation between mortality and mean pulmonary artery pressure.13 Furthermore, pulmonary hypertension is a predictor of requirement for cardiopulmonary bypass. This situation is known to carry greater inflammatory stress and a higher risk of bleeding due to the need for systemic
METHODS
LUNG TRANSPLANTATION AT AGE ⬎60 YEARS
heparinization.14 Because most elderly patients die from infectious complications, every effort should be made to achieve an early diagnosis and provide aggressive treatment.3,15 Despite the lack of literature support, we also believe that the absence of preoperative airway colonization may prevent the development of infectious episodes in the posttransplant period. In our study group, none of the patients presented with airway colonization preoperatively. In previous reports specifically addressing elderly patients undergoing lung transplantation, the results are similarly encouraging. In the cohort of patients ⬎65 years old from the University of California, the 1-year survival was 79.7%, which was comparable to the 91.2% found with younger patients.3 Infectious complications were the main cause of death in the first posttransplant year, raising questions about a specific immunosuppressive protocol for this particular group. In the University of Virginia study addressing patients ⱖ60 years old, there was also a trend for unilateral transplantation. The 86% 1-year survival was similar to that of younger patients.4 According to the ISHLT report, the overall 1-year survival for lung transplantation recipients was 79%, but when exclusively analyzing patients ⬎65 years old, it fell to 72%.1 In summary, our results were similar to those of other transplant teams and to those in the ISHLT registry. The present work reinforced the feasibility of lung transplantation for the treatment of end-stage pulmonary diseases in elderly patients. Again, we stress the crucial role of careful recipient selection and our predilection for single transplantation. REFERENCES 1. Christie JD, Edwards LB, Aurora P, et al: The Registry of the International Society for Heart and Lung Transplantation: Twentysixth official adult lung and heart-lung transplantation report— 2009. J Heart Lung Transplant 28:1031, 2009
235 2. Kreider M, Kotloff RM: Selection of candidates for lung transplantation. Proc Am Thorac Soc 6:20, 2009 3. Mahidhara R, Bastani S, Ross DJ, et al: Lung transplantation in older patients? J Thorac Cardiovasc Surg 135:412, 2008 4. Smith PW, Wang H, Parini V, et al: Lung transplantation in patients 60 years and older: Results, complications and outcomes. Ann Thorac Surg 82:1835, 2006 5. Christie JD, Edwards LB, Aurora P, et al: The Registry of the International Society for Heart and Lung Transplantation: Twentysixth official adult lung and heart-lung transplantation report— 2009. J Heart Lung Transplant 28:1031, 2009 6. Pierre AF, Sekine Y, Hutcheon M, et al: Marginal donor lungs: a reassessment. J Thorac Cardiovasc Surg 123:421, 2002 7. Camargo JJ, Camargo SM, Machuca TN, et al: Surgical maneuvers for the management of bronchial complications lung transplantation. Eur J Cardiothorac Surg 34:1206, 2008 8. Nwakanma LU, Simpkins CE, Williams JA, et al: Impact of bilateral versus single lung transplantation on survival in recipients 60 years of age and older: Analysis of United Network for Organ Sharing database. J Thorac Cardiovasc Surg 133:541, 2007 9. Miñambres E, Llorca J, Suberviola B, et al: Early outcome after single versus bilateral lung transplantation in older recipients. Transplant Procc 40:3088, 2008 10. Fischer S, Meyer K, Tessmann R, et al: Outcome following single vs bilateral lung transplantation in recipients 60 years of age and older. Transplant Procc 37:1369, 2005 11. Meyer DM, Bennett LE, Novick RJ, et al: Single vs bilateral, sequential lung transplantation for end-stage emphysema: influence of recipient age on survival and secondary end-points. J Heart Lung Transplant 20:935, 2001 12. Meyer DM, Edwards LB, Torres F, et al: Impact of recipient age and procedure type on survival after lung transplantation for pulmonary fibrosis. Ann Thorac Surg 79:950, 2005 13. Whelan TPM, Dunitz JM, Kelly RF, et al: Effect of preoperative pulmonary artery pressure on early survival after lung transplantation for idiopathic pulmonary fibrosis. J Heart Lung Transplant 24:1269, 2005 14. Pugliese F, Ruberto F, Ferrazza V, et al: Extracorporeal circulation with low systemic heparinization during lung transplantation. Transplant Proc 38:1167, 2006 15. Gutierrez C, Al-Faifi A, Chaparro C, et al: The effect of recipient’s age on lung transplant outcome. Am J Transplant 7:1271, 2007
B
© 2011 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 43, 233–235 (2011)
benefit from the procedure. Thus, it is accepted that age ⬎65 years is a relative contraindication for lung transplantation.2 However, a few groups have shown favorable lung transplantation results with well-selected patients within this age range.3,4 The aim of this study is to present our experience with this particular population, focusing on recipient selection, early results, and posttransplant complications.
From the Lung Transplantation Group (T.N.M., S.M.C., S.M.S., L.B.S., F.P., J.C.F., J.J.C.), Hospital Dom Vicente Scherer, Santa Casa de Porto Alegre and the Thoracic Surgery Service (T.N.M., S.M.C., V.L., F.P., J.C.F., J.J.C.), Pavilhão Pereira Filho, Santa Casa de Porto Alegre, Porto Alegre, RS, Brazil. Address reprint requests to Tiago Noguchi Machuca, São Francisco da Califórnia street, 222, apto 304, Porto Alegre, Rio Grande do Sul, Brazil, 90550-080. E-mail: machuca36@hotmail. com 0041-1345/–see front matter doi:10.1016/j.transproceed.2010.12.010 233
234
MACHUCA, CAMARGO, SCHIO ET AL
This retrospective study included patients who underwent lung transplantation from January 2004 to February 2009. We reviewed recipient preoperative data, intraoperative features, and data regarding postoperative course. In this period, we performed 112 procedures from cadaveric donors, including 12 (10.7%) recipients ⬎65 years old. Patients were eligible for lung transplantation according to ISHLT criteria.5 Organ procurement was based on conventional methods.6 Our immunosuppressive regimen and surgical technique have been described elsewhere.7 Routine pretransplant evaluation included the performance of coronary angiography and pulmonary artery catheterization.
Due to hemothorax, 2 patients required early reintervention; one of these was the patient with previous LVRS. In the first month, 8 patients had acute rejection episodes, which were diagnosed based on clinicoradiologic findings in 4 and on histologic findings in the remaining 4 cases (grade 2 in 3 and grade 3 in 1 subject). There was only 1 in-hospital mortality due to massive hemoptysis in a patient with a bronchoarterial fistula. The 1-year survival was 75%. Three other patients died due to respiratory infections (n ⫽ 2) in addition to the bronchoarterial fistula (n ⫽ 1).
RESULTS
DISCUSSION
There were 9 male patients and the overall mean age was 68 years (range, 66 –72). The indications were pulmonary fibrosis (n ⫽ 8) and emphysema (n ⫽ 4). The nutritional status of all 12 patients was acceptable, with no case of underweight and 5 cases of overweight individuals; the mean body mass index (BMI) was 25.3 kg/m2 (range, 21.5–29.8). The mean distance in the 6-minute walk test was 308 meters (range, 25– 475). All patients were ambulatory. There was no case of preoperative airway colonization. Regarding pulmonary hemodynamics, only 3 patients had a systolic pulmonary artery pressure ⬎40 mm Hg on pretransplant right heart catheterization (mean, 33 mm Hg; range, 21–50). Comorbidities were present in 7 patients, namely, mild coronary artery disease (n ⫽ 3), systemic arterial hypertension (n ⫽ 3), and both conditions (n ⫽ 1). Seven patients were on oral corticosteroids at the time of transplantation, but in all cases the daily dose was ⬍20 mg of prednisone. All patients underwent single lung transplantation, which was left-sided in 9 cases. Owing to pulmonary hypertension, 2 patients required cardiopulmonary bypass. The mean ischemic time was 222 mimutes (range, 110 –300). Two patients experienced intraoperative bleeding ⬎1500 mL; in both cases, it was due to extensive pleural adhesions. In one case an emphysema patient had previous ipsilateral lung volume reduction surgery (LVRS). Tranfusion of red blood cells was required in 5 cases. Primary graft dysfunction was recorded in 4 cases: moderate in 2 and severe in the remaining 2. Eight patients were extubated within the first 12 postoperative hours. The patients with primary graft dysfunction had a mean requirement of mechanical ventilation of 75 hours. Two patients had no requirement for vasopressors in the immediate postoperative period. The remaining 10 patients required vasoactive drugs for a mean of 26.3 hours. Nine patients developed infectious complications in the early posttransplant period. The site was pulmonary in 8 cases: Pseudomonas aeruginosa (n ⫽ 3), Staphylococcus aureus (n ⫽ 1), or Aspergillus fumigatus (n ⫽ 1). In addition, 3 cases underwent empirical treatment due to no microbiological recovery. In 1 case, it was catheter-related due to methicillin-resistant S aureus. Two patients presented with atrial fibrillation, which was successfully reversed in both.
One of the major points in the discussion about lung transplantation for patients ⬎65 years regards the performance of unilateral versus bilateral procedures. Review of the United Network for Organ Sharing (UNOS) database from 1998 to 2004 revealed 1656 patients of ⱖ60 years who underwent lung transplantation.8 The survival of patients with single-sided procedures was not different from patients undergoing bilateral transplantation. In a single-institutional report of 51 recipients aged ⱖ60 years. The early outcomes were similar between patients who underwent either single or bilateral transplantation, with 30-day survivals of 81% versus 92%, respectively.9 However, other reports have shown the deleterious effects of double-lung transplantations in older patients. In an analysis of 18 patients from the Hannover group, not only the periods of mechanical ventilation and ICU stay were longer in patients with bilateral procedures, but also the 1-year survival was strikingly worse (43% vs 73%).10 When the evaluation was stratified according to indication, there was also a trend for improved outcome for single lung transplantation in older patients with chronic obstructive pulmonary disease. In another UNOS registry analysis, patients up to 60 years showed a survival benefit when submitted to bilateral lung transplantation. Above this age, the 1-year survival fell from 93% (for single transplants) to 77.8% (for bilateral procedures).11 In the setting of patients with pulmonary fibrosis, the 1-year survival for bilateral transplantations in patients ⬎59 years old was also worse (47.7% vs 62.9%).12 Supported by these results and by the greater probability of receiving a graft when listed for a unilateral procedure, specially in areas suffering a donor shortage, it has been our policy to perfom single lung transplantation for older patients with either pulmonary fibrosis or emphysema. In addition to procedure selection, careful recipient selection is also crucial for successful lung transplantation in elderly patients. We believe that 1 major point is pulmonary hemodynamics. Among patients with pulmonary fibrosis undergoing single lung transplantation, there is a linear correlation between mortality and mean pulmonary artery pressure.13 Furthermore, pulmonary hypertension is a predictor of requirement for cardiopulmonary bypass. This situation is known to carry greater inflammatory stress and a higher risk of bleeding due to the need for systemic
METHODS
LUNG TRANSPLANTATION AT AGE ⬎60 YEARS
heparinization.14 Because most elderly patients die from infectious complications, every effort should be made to achieve an early diagnosis and provide aggressive treatment.3,15 Despite the lack of literature support, we also believe that the absence of preoperative airway colonization may prevent the development of infectious episodes in the posttransplant period. In our study group, none of the patients presented with airway colonization preoperatively. In previous reports specifically addressing elderly patients undergoing lung transplantation, the results are similarly encouraging. In the cohort of patients ⬎65 years old from the University of California, the 1-year survival was 79.7%, which was comparable to the 91.2% found with younger patients.3 Infectious complications were the main cause of death in the first posttransplant year, raising questions about a specific immunosuppressive protocol for this particular group. In the University of Virginia study addressing patients ⱖ60 years old, there was also a trend for unilateral transplantation. The 86% 1-year survival was similar to that of younger patients.4 According to the ISHLT report, the overall 1-year survival for lung transplantation recipients was 79%, but when exclusively analyzing patients ⬎65 years old, it fell to 72%.1 In summary, our results were similar to those of other transplant teams and to those in the ISHLT registry. The present work reinforced the feasibility of lung transplantation for the treatment of end-stage pulmonary diseases in elderly patients. Again, we stress the crucial role of careful recipient selection and our predilection for single transplantation. REFERENCES 1. Christie JD, Edwards LB, Aurora P, et al: The Registry of the International Society for Heart and Lung Transplantation: Twentysixth official adult lung and heart-lung transplantation report— 2009. J Heart Lung Transplant 28:1031, 2009
235 2. Kreider M, Kotloff RM: Selection of candidates for lung transplantation. Proc Am Thorac Soc 6:20, 2009 3. Mahidhara R, Bastani S, Ross DJ, et al: Lung transplantation in older patients? J Thorac Cardiovasc Surg 135:412, 2008 4. Smith PW, Wang H, Parini V, et al: Lung transplantation in patients 60 years and older: Results, complications and outcomes. Ann Thorac Surg 82:1835, 2006 5. Christie JD, Edwards LB, Aurora P, et al: The Registry of the International Society for Heart and Lung Transplantation: Twentysixth official adult lung and heart-lung transplantation report— 2009. J Heart Lung Transplant 28:1031, 2009 6. Pierre AF, Sekine Y, Hutcheon M, et al: Marginal donor lungs: a reassessment. J Thorac Cardiovasc Surg 123:421, 2002 7. Camargo JJ, Camargo SM, Machuca TN, et al: Surgical maneuvers for the management of bronchial complications lung transplantation. Eur J Cardiothorac Surg 34:1206, 2008 8. Nwakanma LU, Simpkins CE, Williams JA, et al: Impact of bilateral versus single lung transplantation on survival in recipients 60 years of age and older: Analysis of United Network for Organ Sharing database. J Thorac Cardiovasc Surg 133:541, 2007 9. Miñambres E, Llorca J, Suberviola B, et al: Early outcome after single versus bilateral lung transplantation in older recipients. Transplant Procc 40:3088, 2008 10. Fischer S, Meyer K, Tessmann R, et al: Outcome following single vs bilateral lung transplantation in recipients 60 years of age and older. Transplant Procc 37:1369, 2005 11. Meyer DM, Bennett LE, Novick RJ, et al: Single vs bilateral, sequential lung transplantation for end-stage emphysema: influence of recipient age on survival and secondary end-points. J Heart Lung Transplant 20:935, 2001 12. Meyer DM, Edwards LB, Torres F, et al: Impact of recipient age and procedure type on survival after lung transplantation for pulmonary fibrosis. Ann Thorac Surg 79:950, 2005 13. Whelan TPM, Dunitz JM, Kelly RF, et al: Effect of preoperative pulmonary artery pressure on early survival after lung transplantation for idiopathic pulmonary fibrosis. J Heart Lung Transplant 24:1269, 2005 14. Pugliese F, Ruberto F, Ferrazza V, et al: Extracorporeal circulation with low systemic heparinization during lung transplantation. Transplant Proc 38:1167, 2006 15. Gutierrez C, Al-Faifi A, Chaparro C, et al: The effect of recipient’s age on lung transplant outcome. Am J Transplant 7:1271, 2007