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Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplantation in Patients Over Age 70 Years: A Case Report
Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplantation in Patients Over Age 70 Years: A Case Report J.A. Hayangaa,*, E. Murphyb, R.E. Girgisb,c, S. Jansmac, and A. Khaghanid a Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; bRichard DeVos Heart & Lung Transplant Program, Spectrum Health, Michigan State University, College of Human Medicine, Grand Rapids, Michigan; and c Division of Pulmonary and Critical Care Medicine, Spectrum Health, Michigan State University, College of Human Medicine, Grand Rapids, Michigan; dRichard DeVos Heart & Lung Transplant Program, Spectrum Health, Michigan State University, College of Human Medicine, Grand Rapids, Michigan
ABSTRACT Extracorporeal membrane oxygenation (ECMO) may be used safely as a bridge to lung transplantation in carefully selected elderly patients. We report the case of a 70-yeareold patient bridged on ECMO before transplantation. A brief discussion on improving outcomes for the elderly and patients bridged on ECMO in general is presented.
T
HE NUMBER of patients with end-stage lung disease (ESLD) who are over the age of 65 years is growing with the overall elderly population. However, the therapeutic options offered to these potential lung transplant recipients are few and are subject to close scrutiny. This is specifically because of the prevalent shortage of donors. Many centers are judicious in their use of mechanical support in most age groups, but this is particularly true for elderly patients, whose risk of death is perceived to be the highest. Currently, no reports exist in the literature that describe the use of extracorporeal support as a bridge to lung transplantation (LT) in elderly recipients. We carefully selected a 70-year-old candidate with ESLD and placed him on veno-venous extracorporeal membrane oxygenation (VV-ECMO) under conscious sedation, using this as a bridge to single LT without the need for endotracheal intubation or mechanical ventilation.
Case Presentation
The patient was a 70-year-old man with a 5-year history of idiopathic pulmonary fibrosis who was referred for lung transplantation because of progressive disease. His condition had been deteriorating over the preceding year, with a decline in forced vital capacity from 55% to 42% of predicted and worsening hypoxemia. Despite his worsening symptoms, he continued to participate in pulmonary rehabilitation twice per week, which he had been doing regularly for 4 years. He had a Frailty Score of 4, based on the Canadian Study on Health and Aging [1]. Cardiac evaluation revealed moderate elevation in pulmonary artery 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2016.11.025
218
pressure at 50/19 (mean, 31 mm Hg) but a profoundly reduced cardiac index at 1.22 L/min/m2 body surface area with pulmonary artery wedge pressure of 17 mm Hg and severe elevation in pulmonary vascular resistance at 6.45 WU. Echocardiography demonstrated moderate dilatation of the right ventricle (RV), with significant impairment in RV systolic function as indicated by a tricuspid annular plane systolic excursion of 15 mm and free-wall longitudinal peak strain of 12%. There was systolic and diastolic septal flattening, with a left ventricular (LV) ejection fraction of 55%. He had single-vessel coronary artery disease with 90% stenosis in the mid ramus intermedius, which was deemed not to require intervention. Before completion of the transplant evaluation, the patient was hospitalized with several days of increasing dyspnea associated with cough and purulent sputum production. A spiral CT angiogram of the chest showed no pulmonary embolism or clear airspace consolidation or ground glass opacities. His oxygen requirement had increased further from 4 L/min to 60% high-flow nasal cannula. Broadspectrum antibiotics were initiated, and his evaluation was rapidly completed. His case was then presented before the institutional multidisciplinary selection committee, who approved his candidacy and listed him for transplantation. Ten days later, the patient’s condition deteriorated further, with increased oxygen requirements and tachypnea. *Address correspondence to Jeremiah Awori Hayanga, 330 Barclay Avenue NE, Suite 200, Grand Rapids, MI 49503. E-mail: [email protected] ª 2016 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 49, 218e220 (2017)
ECMO AS A BRIDGE TO LUNG TRANSPLANTATION
He was transferred to the critical care unit, and a decision was made to either transition him to palliative care or to try 36 hours of VV-ECMO in the event that a donor became available. After deliberation, a decision was made to initiate ambulatory VV-ECMO as a bridge for transplant. We used a 31F Avalon Elite (Rancho Dominguez, California, USA) bi-caval dual-lumen cannula placed in the right internal jugular vein under fluoroscopic and trans-esophageal echocardiographic guidance. His Lung Allocation Score was thus increased from 53 to 91, effectively estimating his risk of death at greater than 60% without transplantation. A suitable donor was identified within 24 hours. The donor was a 23-year-old, ABO-identical, brain-dead male donor of suitable height and without a cytomegalovirus (CMV) mismatch (CMVþ/CMVþ). After standard induction with basiliximab, the patient underwent a left singlelung transplant on cardiopulmonary bypass through the use of a posterolateral thoracotomy. The intra-operative course was relatively uneventful, with the exception of the anticipated moderate RV dysfunction. The patient was transferred from the operating room to the critical care unit on high-dose intravenous pressors, inhaled nitric oxide, and intravenous milrinone. To allow for gradual remodeling, and in view of his moderate pulmonary hypertension and to minimize risk of RV strain and primary graft dysfunction, he was maintained on VV-ECMO support after surgery, with a minimal protective lung ventilation strategy. The hemodynamic support was rapidly weaned, and the patient was extubated on postoperative day 1. An elevated creatinine of 1.52, suggestive of acute kidney injury, was noted on postoperative day 2. However, this normalized with increased fluid administration. He was weaned off VVECMO and de-cannulated on postoperative day 3. On the same day, he was noted to have developed atrial fibrillation with rapid ventricular response. Intravenous amiodarone was initiated to allow cardioversion to sinus rhythm. Echocardiography revealed a dilated, hypokinetic RV and pulmonary hypertension. The advanced heart failure service was consulted. The milrinone was weaned off, and sildenafil was initiated instead. The patient remained ambulatory and participated in daily physical therapy. He was transferred out of the intensive care unit to a regular room on postoperative day 7. Standard immune suppression regimen was observed per institutional protocol (including basiliximab induction, and, on postoperative day 4, prednisone burst was administered and subsequently weaned to 25 mg po per day, mycophenolate mofetil 1000 mg bid, and tacrolimus adjusted to a target goal of 10e12). An antimicrobial regimen included treatment for donor cultures that were positive for methicillin-sensitive Staphylococcus aureus, group B streptococcus, and candida, for which the patient completed 14 days of cefazolin. He also received inhaled amphotericin until discharge, when this was switched to oral fluconazole. Finally, the patient received sulfamethoxaole-trimethoprim for primary care physician prophylaxis and valgancyclvir for CMV prophylaxis.
219
The patient resumed sinus rhythm and was weaned off intravenous amiodarone by postoperative day 9. However, he continued to have bursts of atrial tachycardia that were treated with intravenous adenosine and amiodarone. This allowed for maintenance of sinus rhythm without the need for electrical cardioversion. Because this was atrial tachycardia and not atrial fibrillation, it was determined that anticoagulation was not warranted. He remained in sinus rhythm for the remainder of the length of stay. Before discharge, however, the electrocardiogram showed a prolonged corrected QT interval, and amiodarone was discontinued to prevent further prolongation. The patient’s thoracotomy pain was well-controlled throughout his postoperative period. He did not require epidural analgesia and had minimal oral narcotic requirements. At the time of discharge, he was relatively painfree and able to ambulate 1300 feet independently. He and his wife, who was his designated caregiver, received extensive education regarding medication administration along with the institution’s “living with lung transplantation” guidelines. Both showed appropriate understanding of this information at the time of discharge. At 4 months after transplant, the patient was asymptomatic, with a forced expiratory volume in 1 second 85% of predicted. DISCUSSION
For several decades, the International Society of Heart and Lung Transplantation has recommended age 65 years as a cut-off for lung transplantation [2]. This age restriction has also been suggested by the results from analyses of data from the United Network of Organ Sharing and various other reports that largely hinge on the comparatively poor long-term outcomes after LT in this age group [3,4]. However, there is an increase in accrual of data favoring shortterm outcomes in transplantation in the elderly for both heart and lung transplantation [5]. We recently published a report highlighting the improvement in 1-year survival after the transplantation of carefully selected septuagenarians. We established that their outcomes were similar to those of sexagenarians [5]. A growing number of elderly patients currently undergo elective cardiothoracic surgical intervention. This is further evidence of ongoing improvements in surgical outcomes in this age group. It is plausible that current protocols, techniques, and treatment regimens have advanced to a point that they better and more safely accommodate these elderly patients. Furthermore, it is likely that new technologies have enhanced the design of ECMO oxygenators and shortened circuitry and allowed the maintenance of an ambulatory transplant candidate. All of these developments probably have served to broaden the scope of extracorporeal support, and the use of ECMO is therefore no longer considered an absolute contraindication to LT. Indeed, we recently reporteddusing a time-series analysisdthat outcomes after the use of ECMO as a bridge to LT continue to improve steadily [5].
220
Published evidence shows improving trends in survival after LT in both of these categories of patients: the elderly and those bridged with the use of ECMO [5,6]. The combination of the use of mechanical support as a bridge and transplanting older recipients represents the possible confluence of advances that have been made in the care of the elderly and in the administration and management of ambulatory ECMO. To the best of our knowledge, this is the first report of ECMO used as a bridge to LT in this age group. As such, it may signal a paradigm shift that will allow the consideration of carefully selected elderly patientsdwho are free of significant comorbiditiesda short period of ECMO support to serve as a short-term bridge to LT, with emphasis on early extubation, continued ambulation, expedited donor identification, minimizing risk of ventilatorassociated pneumonia, and expeditious transplantation. This is not a reckless recommendation to blindly apply to all elderly patients but is an illustration of a contemporary intervention that may potentially allow for individualized intervention and decision-making that challenge the current status quo.
HAYANGA, MURPHY, GIRGIS ET AL
REFERENCES [1] Rockwood K, Song X, MacKnight C, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ 2005;173: 489e95. [2] Benden C, Goldfarb SB, Edwards LB, et al. The registry of the International Society for Heart and Lung Transplantation: seventeenth official pediatric lung and heart-lung transplantation reporte2014; focus theme: retransplantation. J Heart Lung Transplant 2014;33:1025. [3] Hayes Jr D, Whitson BA, Black SM, et al. Influence of age on survival in adult patients on extracorporeal membrane oxygenation before lung transplantation. J Heart Lung Transplant 2015;34: 832e8. [4] Enger T, Philipp A, Videm V, et al. Prediction of mortality in adult patients with severe acute lung failure receiving veno-venous extracorporeal membrane oxygenation: a prospective observational study. Crit Care 2014;18:R67. [5] Hayanga AJ, Aboagye J, Esper S, et al. Extracorporeal membrane oxygenation as a bridge to lung transplantation in the United States: an evolving strategy in the management of rapidly advancing pulmonary disease. J Thorac Cardiovasc Surg 2015;149: 291e6. [6] Hayanga AJ, Aboagye JK, Hayanga HE, et al. Contemporary analysis of early outcomes after lung transplantation in the elderly using a national registry. J Heart Lung Transplant 2015;34:182e8.
ABSTRACT Extracorporeal membrane oxygenation (ECMO) may be used safely as a bridge to lung transplantation in carefully selected elderly patients. We report the case of a 70-yeareold patient bridged on ECMO before transplantation. A brief discussion on improving outcomes for the elderly and patients bridged on ECMO in general is presented.
T
HE NUMBER of patients with end-stage lung disease (ESLD) who are over the age of 65 years is growing with the overall elderly population. However, the therapeutic options offered to these potential lung transplant recipients are few and are subject to close scrutiny. This is specifically because of the prevalent shortage of donors. Many centers are judicious in their use of mechanical support in most age groups, but this is particularly true for elderly patients, whose risk of death is perceived to be the highest. Currently, no reports exist in the literature that describe the use of extracorporeal support as a bridge to lung transplantation (LT) in elderly recipients. We carefully selected a 70-year-old candidate with ESLD and placed him on veno-venous extracorporeal membrane oxygenation (VV-ECMO) under conscious sedation, using this as a bridge to single LT without the need for endotracheal intubation or mechanical ventilation.
Case Presentation
The patient was a 70-year-old man with a 5-year history of idiopathic pulmonary fibrosis who was referred for lung transplantation because of progressive disease. His condition had been deteriorating over the preceding year, with a decline in forced vital capacity from 55% to 42% of predicted and worsening hypoxemia. Despite his worsening symptoms, he continued to participate in pulmonary rehabilitation twice per week, which he had been doing regularly for 4 years. He had a Frailty Score of 4, based on the Canadian Study on Health and Aging [1]. Cardiac evaluation revealed moderate elevation in pulmonary artery 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2016.11.025
218
pressure at 50/19 (mean, 31 mm Hg) but a profoundly reduced cardiac index at 1.22 L/min/m2 body surface area with pulmonary artery wedge pressure of 17 mm Hg and severe elevation in pulmonary vascular resistance at 6.45 WU. Echocardiography demonstrated moderate dilatation of the right ventricle (RV), with significant impairment in RV systolic function as indicated by a tricuspid annular plane systolic excursion of 15 mm and free-wall longitudinal peak strain of 12%. There was systolic and diastolic septal flattening, with a left ventricular (LV) ejection fraction of 55%. He had single-vessel coronary artery disease with 90% stenosis in the mid ramus intermedius, which was deemed not to require intervention. Before completion of the transplant evaluation, the patient was hospitalized with several days of increasing dyspnea associated with cough and purulent sputum production. A spiral CT angiogram of the chest showed no pulmonary embolism or clear airspace consolidation or ground glass opacities. His oxygen requirement had increased further from 4 L/min to 60% high-flow nasal cannula. Broadspectrum antibiotics were initiated, and his evaluation was rapidly completed. His case was then presented before the institutional multidisciplinary selection committee, who approved his candidacy and listed him for transplantation. Ten days later, the patient’s condition deteriorated further, with increased oxygen requirements and tachypnea. *Address correspondence to Jeremiah Awori Hayanga, 330 Barclay Avenue NE, Suite 200, Grand Rapids, MI 49503. E-mail: [email protected] ª 2016 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 49, 218e220 (2017)
ECMO AS A BRIDGE TO LUNG TRANSPLANTATION
He was transferred to the critical care unit, and a decision was made to either transition him to palliative care or to try 36 hours of VV-ECMO in the event that a donor became available. After deliberation, a decision was made to initiate ambulatory VV-ECMO as a bridge for transplant. We used a 31F Avalon Elite (Rancho Dominguez, California, USA) bi-caval dual-lumen cannula placed in the right internal jugular vein under fluoroscopic and trans-esophageal echocardiographic guidance. His Lung Allocation Score was thus increased from 53 to 91, effectively estimating his risk of death at greater than 60% without transplantation. A suitable donor was identified within 24 hours. The donor was a 23-year-old, ABO-identical, brain-dead male donor of suitable height and without a cytomegalovirus (CMV) mismatch (CMVþ/CMVþ). After standard induction with basiliximab, the patient underwent a left singlelung transplant on cardiopulmonary bypass through the use of a posterolateral thoracotomy. The intra-operative course was relatively uneventful, with the exception of the anticipated moderate RV dysfunction. The patient was transferred from the operating room to the critical care unit on high-dose intravenous pressors, inhaled nitric oxide, and intravenous milrinone. To allow for gradual remodeling, and in view of his moderate pulmonary hypertension and to minimize risk of RV strain and primary graft dysfunction, he was maintained on VV-ECMO support after surgery, with a minimal protective lung ventilation strategy. The hemodynamic support was rapidly weaned, and the patient was extubated on postoperative day 1. An elevated creatinine of 1.52, suggestive of acute kidney injury, was noted on postoperative day 2. However, this normalized with increased fluid administration. He was weaned off VVECMO and de-cannulated on postoperative day 3. On the same day, he was noted to have developed atrial fibrillation with rapid ventricular response. Intravenous amiodarone was initiated to allow cardioversion to sinus rhythm. Echocardiography revealed a dilated, hypokinetic RV and pulmonary hypertension. The advanced heart failure service was consulted. The milrinone was weaned off, and sildenafil was initiated instead. The patient remained ambulatory and participated in daily physical therapy. He was transferred out of the intensive care unit to a regular room on postoperative day 7. Standard immune suppression regimen was observed per institutional protocol (including basiliximab induction, and, on postoperative day 4, prednisone burst was administered and subsequently weaned to 25 mg po per day, mycophenolate mofetil 1000 mg bid, and tacrolimus adjusted to a target goal of 10e12). An antimicrobial regimen included treatment for donor cultures that were positive for methicillin-sensitive Staphylococcus aureus, group B streptococcus, and candida, for which the patient completed 14 days of cefazolin. He also received inhaled amphotericin until discharge, when this was switched to oral fluconazole. Finally, the patient received sulfamethoxaole-trimethoprim for primary care physician prophylaxis and valgancyclvir for CMV prophylaxis.
219
The patient resumed sinus rhythm and was weaned off intravenous amiodarone by postoperative day 9. However, he continued to have bursts of atrial tachycardia that were treated with intravenous adenosine and amiodarone. This allowed for maintenance of sinus rhythm without the need for electrical cardioversion. Because this was atrial tachycardia and not atrial fibrillation, it was determined that anticoagulation was not warranted. He remained in sinus rhythm for the remainder of the length of stay. Before discharge, however, the electrocardiogram showed a prolonged corrected QT interval, and amiodarone was discontinued to prevent further prolongation. The patient’s thoracotomy pain was well-controlled throughout his postoperative period. He did not require epidural analgesia and had minimal oral narcotic requirements. At the time of discharge, he was relatively painfree and able to ambulate 1300 feet independently. He and his wife, who was his designated caregiver, received extensive education regarding medication administration along with the institution’s “living with lung transplantation” guidelines. Both showed appropriate understanding of this information at the time of discharge. At 4 months after transplant, the patient was asymptomatic, with a forced expiratory volume in 1 second 85% of predicted. DISCUSSION
For several decades, the International Society of Heart and Lung Transplantation has recommended age 65 years as a cut-off for lung transplantation [2]. This age restriction has also been suggested by the results from analyses of data from the United Network of Organ Sharing and various other reports that largely hinge on the comparatively poor long-term outcomes after LT in this age group [3,4]. However, there is an increase in accrual of data favoring shortterm outcomes in transplantation in the elderly for both heart and lung transplantation [5]. We recently published a report highlighting the improvement in 1-year survival after the transplantation of carefully selected septuagenarians. We established that their outcomes were similar to those of sexagenarians [5]. A growing number of elderly patients currently undergo elective cardiothoracic surgical intervention. This is further evidence of ongoing improvements in surgical outcomes in this age group. It is plausible that current protocols, techniques, and treatment regimens have advanced to a point that they better and more safely accommodate these elderly patients. Furthermore, it is likely that new technologies have enhanced the design of ECMO oxygenators and shortened circuitry and allowed the maintenance of an ambulatory transplant candidate. All of these developments probably have served to broaden the scope of extracorporeal support, and the use of ECMO is therefore no longer considered an absolute contraindication to LT. Indeed, we recently reporteddusing a time-series analysisdthat outcomes after the use of ECMO as a bridge to LT continue to improve steadily [5].
220
Published evidence shows improving trends in survival after LT in both of these categories of patients: the elderly and those bridged with the use of ECMO [5,6]. The combination of the use of mechanical support as a bridge and transplanting older recipients represents the possible confluence of advances that have been made in the care of the elderly and in the administration and management of ambulatory ECMO. To the best of our knowledge, this is the first report of ECMO used as a bridge to LT in this age group. As such, it may signal a paradigm shift that will allow the consideration of carefully selected elderly patientsdwho are free of significant comorbiditiesda short period of ECMO support to serve as a short-term bridge to LT, with emphasis on early extubation, continued ambulation, expedited donor identification, minimizing risk of ventilatorassociated pneumonia, and expeditious transplantation. This is not a reckless recommendation to blindly apply to all elderly patients but is an illustration of a contemporary intervention that may potentially allow for individualized intervention and decision-making that challenge the current status quo.
HAYANGA, MURPHY, GIRGIS ET AL
REFERENCES [1] Rockwood K, Song X, MacKnight C, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ 2005;173: 489e95. [2] Benden C, Goldfarb SB, Edwards LB, et al. The registry of the International Society for Heart and Lung Transplantation: seventeenth official pediatric lung and heart-lung transplantation reporte2014; focus theme: retransplantation. J Heart Lung Transplant 2014;33:1025. [3] Hayes Jr D, Whitson BA, Black SM, et al. Influence of age on survival in adult patients on extracorporeal membrane oxygenation before lung transplantation. J Heart Lung Transplant 2015;34: 832e8. [4] Enger T, Philipp A, Videm V, et al. Prediction of mortality in adult patients with severe acute lung failure receiving veno-venous extracorporeal membrane oxygenation: a prospective observational study. Crit Care 2014;18:R67. [5] Hayanga AJ, Aboagye J, Esper S, et al. Extracorporeal membrane oxygenation as a bridge to lung transplantation in the United States: an evolving strategy in the management of rapidly advancing pulmonary disease. J Thorac Cardiovasc Surg 2015;149: 291e6. [6] Hayanga AJ, Aboagye JK, Hayanga HE, et al. Contemporary analysis of early outcomes after lung transplantation in the elderly using a national registry. J Heart Lung Transplant 2015;34:182e8.