Advertisement

Extracorporeal membrane oxygenation as a bridge to lung transplantation: A single-center experience in the present era

Open ArchivePublished:July 31, 2017DOI:https://doi.org/10.1016/j.jtcvs.2017.06.063

      Abstract

      Objective

      Extracorporeal membrane oxygenation has been used as a bridge to lung transplantation in patients with rapid pulmonary function deterioration. The reported success of this modality and perioperative and functional outcomes are varied.

      Methods

      We retrospectively reviewed all patients who underwent lung transplantation at our institution over 1 year (January 1, 2015, to December 31, 2015). Patients were divided into 2 groups depending on whether they required extracorporeal membrane oxygenation support as a bridge to transplant; preoperative characteristics, lung transplantation outcomes, and survival were compared between groups.

      Results

      Of the 93 patients, 12 (13%) received bridge to transplant, and 81 (87%) did not. Patients receiving bridge to transplant were younger, had higher lung allocation scores, had lower functional status, and were more often on mechanical ventilation at listing. Most patients who received bridge to transplant (n = 10, 83.3%) had pulmonary fibrosis. Mean pretransplant extracorporeal membrane oxygenation support was 103.6 hours in duration (range, 16-395 hours). All patients who received bridge to transplant were decannulated immediately after lung transplantation but were more likely to return to the operating room for secondary chest closure or rethoracotomy. Grade 3 primary graft dysfunction within 72 hours was similar between groups. Lung transplantation success and hospital discharge were 100% in the bridge to transplant group; however, these patients experienced longer hospital stays and higher rates of discharge to acute rehabilitation. The 1-year survival was 100% in the bridge to transplant group and 91% in the non–bridge to transplant group (log-rank, P = .24). The 1-year functional status was excellent in both groups.

      Conclusions

      Extracorporeal membrane oxygenation can be used to safely bridge high-acuity patients with end-stage lung disease to lung transplantation with good 30-day, 90-day, and 1-year survival and excellent 1-year functional status. Long-term outcomes are being studied.

      Key Words

      Abbreviations and Acronyms:

      AT (antithrombin), BTT (bridge to transplantation), CPB (cardiopulmonary bypass), DVT (deep vein thrombosis), ECMO (extracorporeal membrane oxygenation), LAS (lung allocation score), LTx (lung transplantation), UNOS (United Network for Organ Sharing), VA (venoarterial), VV (venovenous)
      Figure thumbnail fx1
      Artist's depiction of VV ECMO dual-lumen Avalon cannula. Used with permission from Norton Thoracic Institute, Phoenix, Arizona.
      ECMO can be safely used as a bridge to LTx with high success rates and good short-term survival in select high-acuity patients with end-stage lung disease.
      ECMO can be used as bridge therapy in select critically ill patients who experience acute deterioration while awaiting LTx. Good short-term outcomes regarding primary graft dysfunction rates, 1-year survival, and 1-year functional status can be achieved in select high-acuity patients.
      See Editorial Commentary page 1810.
      See Editorial page 1796.
      Mechanical ventilation is the traditional method of respiratory support for patients with end-stage lung disease awaiting lung transplantation (LTx), but it is not sufficient for all patients
      • George T.J.
      • Beaty C.A.
      • Kilic A.
      • Shah P.D.
      • Merlo C.A.
      • Shah A.S.
      Outcomes and temporal trends among high-risk patients after lung transplantation in the United States.
      • Yusen R.D.
      • Edwards L.B.
      • Kucheryavaya A.Y.
      • Benden C.
      • Dipchand A.I.
      • Dobbels F.
      • et al.
      The Registry of the International Society for Heart and Lung Transplantation: Thirty-First Adult Lung and Heart-Lung Transplant Report-2015; Focus Theme: Early Graft Failure.
      • Singer J.P.
      • Blanc P.D.
      • Hoopes C.
      • Golden J.A.
      • Koff J.L.
      • Leard L.E.
      • et al.
      The impact of pre-transplant mechanical ventilation on short- and long-term survival after lung transplantation.
      • Gottlieb J.
      • Warnecke G.
      • Hadem J.
      • Dierich M.
      • Wiesner O.
      • Fühner T.
      • et al.
      Outcome of critically ill lung transplant candidates on invasive respiratory support.
      and is associated with potentially devastating complications, such as ventilator-acquired pneumonia or ventilator-induced lung injury. Extracorporeal membrane oxygenation (ECMO) is an alternative to mechanical ventilation that can provide respiratory support as a bridge therapy while a patient awaits a suitable donor for LTx.
      • Lang G.
      • Taghavi S.
      • Aigner C.
      • Renyi-Vamos F.
      • Jaksch P.
      • Augustin V.
      • et al.
      Primary lung transplantation after bridge with extracorporeal membrane oxygenation: a plea for a shift in our paradigms for indications.
      This technology and the experience levels of those operating it have evolved over the past few decades, and several centers now use ECMO as a bridge to transplantation (BTT).
      • Hoopes C.W.
      • Kukreja J.
      • Golden J.
      • Davenport D.L.
      • Diaz-Guzman E.
      • Zwischenberger J.B.
      Extracorporeal membrane oxygenation as a bridge to pulmonary transplantation.
      • Toyoda Y.
      • Bhama J.K.
      • Shigemura N.
      • Zaldonis D.
      • Pilewski J.
      • Crespo M.
      • et al.
      Efficacy of extracorporeal membrane oxygenation as s bridge to lung transplantation.
      • Rehder K.J.
      • Turner D.A.
      • Hartwig M.G.
      • Williford W.L.
      • Bonadonna D.
      • Walczak Jr., R.J.
      • et al.
      Active rehabilitation during extracorporeal membrane oxygenation as a bridge to lung transplantation.
      • Shafii A.
      • Mason D.P.
      • Brown C.R.
      • Vakil N.
      • Johnston D.R.
      • Mccurry K.R.
      • et al.
      Growing experience with extracorporeal membrane oxygenation as a bridge to lung transplantation.
      • Javidfar J.
      • Brodie D.
      • Iribarne A.
      • Jurado J.
      • LaVelle M.
      • Brenner K.
      • et al.
      Extracorporeal membrane oxygenation as a bridge to lung transplantation and recovery.
      • Abrams D.
      • Javidfar J.
      • Farrand E.
      • Mongero L.B.
      • Agerstrand C.L.
      • Ryan P.
      • et al.
      Early mobilization of patients receiving extracorporeal membrane oxygenation: a retrospective cohort study.
      LTx outcomes after ECMO BTT vary on the basis of institutional practices.
      • Shafii A.
      • Mason D.P.
      • Brown C.R.
      • Vakil N.
      • Johnston D.R.
      • Mccurry K.R.
      • et al.
      Growing experience with extracorporeal membrane oxygenation as a bridge to lung transplantation.
      Although survival in patients who receive ECMO BTT has been reported to be lower than in non-BTT transplant recipients,
      • George T.J.
      • Beaty C.A.
      • Kilic A.
      • Shah P.D.
      • Merlo C.A.
      • Shah A.S.
      Outcomes and temporal trends among high-risk patients after lung transplantation in the United States.
      • Inci I.
      • Klinzing S.
      • Schneiter D.
      • Schuepbach R.A.
      • Kestenholz P.
      • Hillinger S.
      • et al.
      Outcome of extracorporeal membrane oxygenation as a bridge to lung transplantation: an institutional experience and literature review.
      the risks are not prohibitive.
      • Mason D.P.
      • Thuita L.
      • Nowicki E.R.
      • Murthy S.C.
      • Pettersson G.B.
      • Blackstone E.H.
      Should lung transplantation be performed for patients on mechanical respiratory support? The US experience.
      As the number and overall survival of patients receiving ECMO and undergoing LTx continue to increase,
      • Hayes Jr., D.
      • Tobias J.D.
      • Tumin D.
      Center volume and extracorporeal membrane oxygenation support at lung transplantation in the Lung Allocation Score Era.
      several centers have achieved better ECMO BTT survival that is comparable to that of patients without BTT.
      • Hoopes C.W.
      • Kukreja J.
      • Golden J.
      • Davenport D.L.
      • Diaz-Guzman E.
      • Zwischenberger J.B.
      Extracorporeal membrane oxygenation as a bridge to pulmonary transplantation.
      • Toyoda Y.
      • Bhama J.K.
      • Shigemura N.
      • Zaldonis D.
      • Pilewski J.
      • Crespo M.
      • et al.
      Efficacy of extracorporeal membrane oxygenation as s bridge to lung transplantation.
      However, most centers are selective in using this approach, and many will use ECMO BTT only for patients who are already listed for LTx and who have good potential for rehabilitation.
      • Rehder K.J.
      • Turner D.A.
      • Hartwig M.G.
      • Williford W.L.
      • Bonadonna D.
      • Walczak Jr., R.J.
      • et al.
      Active rehabilitation during extracorporeal membrane oxygenation as a bridge to lung transplantation.
      • Abrams D.
      • Javidfar J.
      • Farrand E.
      • Mongero L.B.
      • Agerstrand C.L.
      • Ryan P.
      • et al.
      Early mobilization of patients receiving extracorporeal membrane oxygenation: a retrospective cohort study.
      Nationwide registries have reported ECMO BTT to be more successful at high-volume LTx centers in the recent era,
      • Hayes Jr., D.
      • Tobias J.D.
      • Tumin D.
      Center volume and extracorporeal membrane oxygenation support at lung transplantation in the Lung Allocation Score Era.
      • Hayanga A.J.
      • Aboagye J.
      • Esper S.
      • Shigemura N.
      • Bermudez C.A.
      • D'Cunha J.
      • 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.
      and ECMO deployment algorithms have been implemented with some success.
      The 2005 implementation of the lung allocation score (LAS) system led to a dramatic increase in the proportion and number of transplants in high-acuity patients,
      • Iribarne A.
      • Russo M.J.
      • Davies R.R.
      • Hong K.N.
      • Gelijns A.C.
      • Bacchetta M.D.
      • et al.
      Despite decreased wait-list times for lung transplantation, lung allocation scores continue to increase.
      including those on life support with ECMO or mechanical ventilation. The post-LAS era has seen decreasing numbers of waitlist deaths and increasing numbers of annual LTx procedures.
      • Valapour M.
      • Skeans M.A.
      • Smith J.M.
      • Edwards L.B.
      • Cherikh W.S.
      • Callahan E.R.
      • et al.
      OPTN/SRTR Annual data report 2014: Lung.
      However, patients with fibrotic lung disease often experience acute deterioration while awaiting LTx, and this deterioration necessitates hospitalization and respiratory support, sometimes in the form of ECMO.
      In this study, we retrospectively reviewed the outcomes of all patients who underwent LTx at our high-volume institution over a single calendar year, just after the implementation of a comprehensive, multidisciplinary ECMO program. We compared the outcomes of all patients who received ECMO BTT during the study period with those of patients who did not receive BTT during the same period and compared the outcomes of patients who received ECMO BTT after our program initiation with the outcomes of patients who received ECMO BTT before this program began.

      Materials and Methods

       Study Design

      This study was approved by the Institutional Review Board at St Joseph's Hospital and Medical Center in Phoenix, Arizona. We retrospectively reviewed all patients who underwent LTx at our institution over a single calendar year (January 1, 2015, to December 31, 2015), evaluating patients who received ECMO BTT after implementation of a comprehensive ECMO program. We compared the outcomes of patients who received ECMO BTT with those who did not and compared those who received ECMO BTT with those who received ECMO BTT during the 2011 to 2014 calendar years (ie, before the implementation of our dedicated ECMO program).
      We analyzed reasons for ECMO implementation; duration of pre-LTx ECMO; procedure details; survival to transplant for patients who received ECMO BTT bridged with “intent to transplant”; post-LTx outcomes, including length of stay; post-LTx survival at 30 days, 90 days, and 1 year; and functional status at 1 year post-LTx. We also compared rates of delirium (defined according to the American Psychiatric Institution's Diagnostic and Statistical Manual, 5th Edition, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) and critical illness myopathy (diagnosed by generalized muscle weakness or failure to wean from ventilator
      • Tabarki B.
      • Coffinieres A.
      • Van den Bergh P.
      • Huault G.
      • Landrieu P.
      • Sebire G.
      Critical illness neuromuscular disease: clinical, electrophysiological, and prognostic aspects.
      ) between groups. We compared parameters between those who received ECMO BTT and those who did not during the study period. We also identified a historical ECMO BTT cohort, which included all ECMO BTT cases before 2015 at our institution. The historical cohort was compared with the 2015 ECMO BTT cohort for differences in baseline characteristics, success of BTT, and survival.
      Our multidisciplinary ECMO program was established in January 2015 after 3 main phases: physician and staff education, upgrades to technology, and clarification of communication. Our physicians and perfusionists attended a course held by the Extracorporeal Life Support Organization and attended a local education program that involved respiratory therapists and nurses from the intensive care unit. Our institution acquired a new ECMO circuit (Cardiohelp, Maquet Cardiovascular LLC, Wayne, NJ) and transitioned to using a dual-lumen venovenous (VV) cannula (Avalon Elite, Maquet Cardiovascular LLC). Our communication systems were vastly improved after making clear the responsibilities of various practitioners and delineating a clear communication pathway between 2 dedicated perfusionists and the on-call ECMO physician.

       Extracorporeal Membrane Oxygenation Indications and Institutional Practice

      At our institution, the decision to place any patient on ECMO as BTT is made by the ECMO team and is based on speed of deterioration and need for further oxygenation or ventilation despite maximum medical therapy. Our multidisciplinary team comprises LTx pulmonologists and surgeons, perfusionists, pharmacists, a psychiatrist, physical therapists, respiratory therapists, and nurses trained in adult ECMO. The most important factors we consider before placing a transplant candidate on ECMO BTT are physiologic age less than 65 years, ambulatory functional status before deterioration, no other organ dysfunction, and good potential for rehabilitation. Perfusionists have been designated as point-persons and are responsible for overseeing the ECMO program, including implementing and communicating new policies and procedures in collaboration with the surgical and medical directors of the program. Perfusionists are responsible for maintaining an ongoing education program, attending regular multidisciplinary meetings, and rounding at least twice each day on any patient on ECMO. When instability occurs with a patient for any reason, the perfusionist remains at the bedside.

       Procedure

      If circulatory support is not required, we prefer to place patients on VV ECMO using the dual-lumen VV catheter (Avalon Elite, Figure 1). If circulatory support is needed, as was the case for 1 patient in this study, venoarterial (VA) cannulation is used. Ideally, the patient is in the operating room for this procedure, which ensures that both transesophageal echocardiogram and fluoroscopy are available. The jugular vein is accessed, and a guidewire is passed into the inferior vena cava (Video 1). Care must be taken to ensure that the guidewire does not pass into the right ventricle, the coronary sinus, or 1 of the hepatic veins. These structures generally can be avoided using fluoroscopy, but transesophageal echocardiography can visualize critical anatomy. The tract is dilated, and the dual-lumen cannula is positioned so that the distal port is in the inferior vena cava and the outflow cannula, which carries oxygenated blood, is directed into the right ventricle. The cannula must be well secured (usually after removal of the shoulder roll) to avoid movement or displacement once correct placement has been confirmed.
      Figure thumbnail fx2
      Video 1Video describing the role of ECMO as a BTT and a short video of a cannulation for ECMO. Used with permission from Norton Thoracic Institute, Phoenix, Arizona. Video available at: http://www.jtcvsonline.org/article/S0022-5223(17)31579-9/fulltext.
      Figure thumbnail gr1
      Figure 1Artist's depiction of VV ECMO dual-lumen Avalon cannula (Maquet, Rastatt, Germany). ECMO, Extracorporeal membrane oxygenation.
      Used with permission from Norton Thoracic Institute, Phoenix, Arizona.
      In this study, patients were maintained on VV ECMO during LTx unless hemodynamic support was compromised, in which case the patient was converted to cardiopulmonary bypass (CPB) for the implantation procedure. Conversion to CPB was achieved by first cannulating the aorta and attaching the arterial line to the CPB system. The Avalon cannula was converted to venous drainage by attaching a Y connector to the inlet and outlet port of the Avalon cannula in a sterile fashion. The other end of the Y was then attached to the venous line of the CPB system.

       Statistical Analysis

      Demographic and clinical characteristics were assessed using medians and interquartile ranges for continuous variables. Categoric variables were analyzed using frequencies and percentages. All continuous variables were studied using the Shapiro–Wilk Test for normality and assessed graphically. Because of the non-normal distribution of the continuous variables and the small sample size, the Wilcoxon rank-sum and Fisher exact tests were used to compare continuous and categoric variables, respectively. Probabilities of survival were estimated using Kaplan–Meier for the ECMO BTT and non-BTT groups. In addition, survival probabilities were estimated for the historical ECMO BTT and present ECMO BTT groups. The log-rank test was implemented to observe differences in probabilities of survival between ECMO BTT and non-BTT, as well as between the historical BTT and present ECMO BTT groups. All P values were 2-sided. Statistical analysis was performed using Stata 2015, Release 14 (StataCorp LP, College Station, Tex).

      Results

      Of the 93 patients who underwent LTx between January 1, 2015, and December 31, 2015, 12 (13%) were bridged to transplant with ECMO (ie, the ECMO BTT group) and 81 (87%) underwent LTx without ECMO BTT (ie, the non-BTT group). Eleven of the 12 patients receiving ECMO BTT were placed on ECMO after acute respiratory failure with hypoxia, hypercarbia, or both. The remaining patient was placed on ECMO after a brief period of cardiac arrest; emergency VA ECMO was initiated at the bedside.
      Clinical characteristics and comparisons between the baseline characteristics of patients who received and did not receive ECMO BTT are summarized in Table 1. Patients who received ECMO BTT were younger (P = .02), had higher LAS (P < .001), had lower functional status (P < .001), and were more likely to be on ventilator support at the time of listing for LTx (P < .001). A total of 10 of 12 patients who received ECMO BTT (83.3%) were categorized in the United Network for Organ Sharing (UNOS) Group D

      Policy 10 Allocation of Lungs. Organ Procurement and transplantation network (OPTN) policies. Available at: https://optn.transplant.hrsa.gov/media/1200/optn_policies.pdf#nameddest=Policy_10. Accessed September 1, 2016.

      ; just 46 of 81 patients who did not receive ECMO BTT (56.8%) were in this category (P = .07). The median waitlist time was 7.5 days (range, 2-367 days) in the ECMO BTT group compared with 10 days (range, 1-102 days) in the non-BTT group (P = .44).
      Table 1Clinical characteristics of 93 patients with end-stage lung disease who underwent lung transplantation during the study period with and without extracorporeal membrane oxygenation as bridge to transplantation
      Variables
      All continuous variables reported as median (interquartile range).
      Overall (n = 93)Non-BTT (n = 81)BTT (n = 12)P value
      Wilcoxon rank-sum and Fisher exact were used to compare continuous and categoric variables, respectively.
      Median age at transplant, y (IQR)62 (55-68)63 (56-68)56 (45.5-61).02
      Sex, male, n (%)59 (63.4)49 (60.5)10 (83.3).19
      Race, n (%).20
       White71 (76.3)62 (76.5)9 (75.0)
       African American3 (3.2)3 (3.7)0 (0)
       Hispanic14 (15.1)13 (16.0)1 (8.3)
       Native American1 (1.1)0 (0)1 (8.3)
       Other4 (4.3)5 (3.7)1 (8.3)
      UNOS disease group, n (%)
      Group definition based on UNOS policy 10.1.F.i Lung disease diagnosis groups.
      .07
       A27 (29.0)26 (32.1)1 (8.3)
       B2 (2.2)2 (2.5)0 (0)
       C4 (4.3)3 (3.7)1 (8.3)
       D55 (59.1)45 (55.6)10 (83.3)
      Redo LTx5 (5.4)5 (6.1)0 (0)
      Median pretransplant BMI, kg/m2 (IQR)25 (22.5-30)25 (22.5-29.9)26.5 (23.4-31.8).42
      Median LAS (IQR)40.7 (34.6-55.1)38.9 (33.9-52.0)83.7 (53.2-90.1)<.001
      Median Karnofsky score at listing (IQR)50 (30-60)60 (40-60)20 (10-20)<.001
      Median systolic PAP (IQR)38 (32-49)38 (32-49)37.5 (29-51).77
      Median diastolic PAP (IQR)16 (11-20)16 (11-20)14.5 (12-19.5).84
      Mean PAP, median (IQR)25 (21-32)25 (21-32)28.5 (23.5-34).32
      Ventilated at listing, n (%)13 (13.9)5 (6.2)8 (66.7)<.001
      Median FEV1 at listing (IQR)34 (22-51)36 (21.5-51.5)33 (25-47).79
      Median FVC % at listing (IQR)49.5 (38-66)50 (39.5-68.5)37.5 (21-46)
      Data were missing for 2 patients who were too sick to undergo full pretransplant pulmonary testing.
      .01
      Median days on waitlist (IQR)9 (4-19)10 (4-22)7.5 (4.5-11).44
      BTT, Bridge to transplant; IQR, interquartile range; UNOS, United Network for Organ Sharing; LTx, lung transplantation; BMI, body mass index; LAS, lung allocation score; PAP, pulmonary artery pressure; FEV1, forced expiratory volume in 1 second % predicted value; FVC, forced vital capacity % predicted value.
      All continuous variables reported as median (interquartile range).
      Wilcoxon rank-sum and Fisher exact were used to compare continuous and categoric variables, respectively.
      Group definition based on UNOS policy 10.1.F.i Lung disease diagnosis groups.
      § Data were missing for 2 patients who were too sick to undergo full pretransplant pulmonary testing.
      All 12 patients were placed on ECMO with intent to transplant, all received an organ offer within 16 days of being placed on ECMO, and all successfully underwent transplantation during the study period, resulting in a BTT success rate of 100%. Table 2 lists the characteristics of the 12 patients who received ECMO BTT. The median LAS in the ECMO BTT group was 83.7 (range, 34.6-91.2). Ten of the 12 patients in this group had pulmonary fibrosis (UNOS group D), 1 patient had cystic fibrosis, and 1 patient had antisynthetase syndrome (ECMO was used for acute fulminant exacerbation in this patient). A total of 8 of 12 patients (66.7%) were on some form of invasive ventilator support at the time of listing for LTx, although evaluation for LTx had been started in all but 1 patient before initiation of ECMO. The patient with antisynthetase syndrome was transferred to our facility after being placed on ECMO elsewhere.
      Table 2Characteristics of patients who underwent lung transplantation with extracorporeal membrane oxygenation as bridge to transplantation in 2015
      PatientAge, yDiagnosisLASECMO duration, hLOS after LTx, dPost-LTx Karnofsky scale functional status score
      Score of 50-70 on the Karnofsy Performance Status (KPS) Scale signifies inability to work, but living at home and able to care for most personal needs. Score of 80-100 signifies ability to carry out normal activity and work with no assistance needed.
      151IPF90573390
      251IPF/PH90451690
      325CF901663090
      458IPF871071690
      523IPF432472690
      668IPF89384470
      7
      Of the 12 patients in this study, this patient was the only patient who underwent venoarterial ECMO instead of venovenous ECMO.
      59IPF611610080
      857IPF50182790
      955IPF88492390
      1066IPF67271880
      1163IPF86781490
      1241Antisynthetase syndrome4339520100
      LAS, Lung allocation score; ECMO, extracorporeal membrane oxygenation; LOS, length of stay; LTx, lung transplantation; IPF, idiopathic pulmonary fibrosis; PH, pulmonary hypertension; CF, cystic fibrosis.
      Score of 50-70 on the Karnofsy Performance Status (KPS) Scale signifies inability to work, but living at home and able to care for most personal needs. Score of 80-100 signifies ability to carry out normal activity and work with no assistance needed.
      Of the 12 patients in this study, this patient was the only patient who underwent venoarterial ECMO instead of venovenous ECMO.
      The median duration of ECMO support was 53 hours (range, 16-395 hours). A total of 11 of 12 patients (92%) received VV ECMO for severe hypoxia, and 1 of 12 patients received VA ECMO for sudden cardiac arrest and high pulmonary artery pressures as previously mentioned. A bicaval dual-lumen catheter (27F or 31F; Avalon Elite) placed through the right internal jugular vein was used in 9 of 11 patients in the VV ECMO group (82%); 2 of 11 patients in the VV ECMO group had internal jugular–femoral vein cannulation performed in the intensive care unit for more urgent ECMO. These were placed at the bedside because the patients were deemed too unstable for transport to the operating room. The sole patient placed on VA ECMO had femoral vein–femoral artery cannulation. A total of 7 of 12 patients (58%) underwent concomitant tracheostomy at the time of ECMO initiation. Another 2 patients required tracheostomy post-transplant.
      There were no deaths while on the ECMO circuit. A total of 3 of 12 patients (25%) were awake with no sedation or light sedation, and 1 patient was able to transition to a chair at the bedside. No patients were able to ambulate while on ECMO during this period. The remaining 9 of 12 patients required continuous sedation because of agitation and air hunger, with resulting changes in flows on the ECMO circuit. Four patients in the ECMO BTT group (33%) underwent LTx while on the ECMO circuit, whereas 8 patients were converted to CPB (67%). ECMO or CPB was weaned at the conclusion of the transplant procedure in the operating room for all 12 patients, and all patients were decannulated at the end of the transplant procedure in the operating room.
      Table 3 compares intraoperative characteristics and postoperative outcomes in the ECMO BTT and non-BTT groups. In both groups, most LTx procedures were double LTx (ECMO BTT: 100%; non-BTT: 93%). Intraoperative transfusions (both total and packed red blood cell) were higher in the ECMO BTT group (P = .001, P < .001, respectively), as were post-transplant packed red blood cell transfusions (P = .05). A higher proportion of patients in the ECMO BTT group required return to the operating room than patients in the non-BTT group (P = .02), mainly for secondary closure of open chest. Grade 3 primary graft dysfunction (per the standards set forth by the International Society of Heart and Lung Transplantation) at 48 to 72 hours post-transplant were comparable in both groups (P = .72). Rates of delirium and critical illness myopathy were significantly higher in the BTT group (P = .007, P < .001, respectively). The ECMO BTT group had a higher number of bronchoscopies during the transplant stay.
      Table 3Perioperative and postoperative complications in patients who underwent lung transplantation between January 1, 2015, and December 31, 2015, with or without bridge to transplantation with extracorporeal membrane oxygenation
      Variables
      All continuous variables reported as median (IQR).
      Overall (n = 93)Non-BTT (n = 81)BTT (n = 12)P value
      Wilcoxon rank-sum and Fisher exact tests were used to compare continuous and categoric variables, respectively.
      Double LTx, n (%)90 (96.7)78 (96.3)12 (100.0)>.99
      CPB usage, n (%)23 (24.7)15 (15.8)8 (66.6)
      Transitioned to CPB during transplant; remaining 4 of 12 transplants were performed on ECMO.
      .001
      First lung ischemic time, median (IQR)229 (195-257)229 (197-258)237 (123.5-247.5).37
      Second lung ischemic time, median (IQR)
      For double LTx cases.
      287 (255-323)289.5 (258-334)259 (176-313.5).11
      PGD grade 3 at 48-72 h, n (%)25 (26.9)21 (25.9)4 (33.3).72
      ECMO for PGD, n (%)2 (2.2)2 (2.5)0 (0)>.99
      Intraoperative PRBC transfusion, median (IQR)3 (1-5)2 (1-4)6 (3.5-9)<.001
      Intraoperative total blood products transfusions, median (IQR)4 (1-15)3 (1-12)24.5 (6-29).001
      Postoperative PRBC transfusion, median (IQR)1 (0-3)1 (0-2)2.5 (0.5-8).05
      Return to OR, n (%)21 (22.6)13 (16.1)8 (66.7).001
      Reintubation post-transplant, n (%)6 (6.5)5 (6.2)1 (9.3).57
      Tracheostomy post-transplant, n (%)8 (8.6)6 (7.4)2 (16.7).27
      Pneumonia, n (%)11 (11.8)9 (11.1)2 (16.7).63
      Post-transplant bronchoscopies during hospital stay, median (IQR)3 (2-4)3 (2-4)3.5 (3-6).04
      Total LOS, median (IQR)17 (11-30)15 (11-26)39 (32.5-50.5)<.001
      Post-transplant LOS, median (IQR)15 (10-19)13 (10-17)25 (18-31)<.001
      30-d mortality, n (%)1 (1.1)1 (1.2)0 (0)>.99
      Disposition at discharge, n (%).001
       Home59 (63.4)57 (70.4)2 (16.7)
       IPR/SNF34 (36.6)24 (29.6)10 (93.3)
      Delirium, n (%)17 (18.3)11 (13.5)6 (50).01
      Myopathy, n (%)20 (21.5)10 (12.3)10 (83.3)<.001
      Thrombotic event, n (%)21 (22.6)15 (18.5)6 (50).03
      Survival at 1 y, n (%)85/92 (92.4)73/80 (91.3)12/12 (100)1.0
      BTT, Bridge to transplant; LTx, lung transplantation; CPB, cardiopulmonary bypass; IQR, interquartile range; PGD, primary graft dysfunction; ECMO, extracorporeal membrane oxygenation; PRBC, packed red blood cells; OR, operating room; LOS, length of stay; IPR, inpatient rehabilitation; SNF, skilled nursing facility.
      All continuous variables reported as median (IQR).
      Wilcoxon rank-sum and Fisher exact tests were used to compare continuous and categoric variables, respectively.
      Transitioned to CPB during transplant; remaining 4 of 12 transplants were performed on ECMO.
      § For double LTx cases.
      A higher proportion of patients in the ECMO BTT group had venous thrombotic events during their hospital stays for LTx (n = 6; P = .03). One ECMO circuit thrombosis occurred as a result of low initial antithrombin (AT) levels (39%); this required changing the circuit within the first 24 hours of ECMO initiation. All other venous thrombotic events in the ECMO BTT group were postoperative: Deep vein thrombosis (DVT) developed in 4 patients, and pulmonary embolism developed in 1 patient. Total and post-LTx length of hospital stay were both higher in the ECMO BTT group (P < .001). There were no in-hospital deaths in the ECMO BTT group. Rates of pneumonia post-transplant were comparable between the 2 groups. A higher proportion of those in the ECMO BTT group required acute rehabilitation after discharge (P = .001). However, functional status 1 year post-transplant was comparable between groups (P = .74). Thirty-day, 90-day, and 1-year survivals were 100%, 100%, and 100% in the ECMO BTT group and 98.8%, 97.5%, and 91.3% in the non-BTT group, respectively (P > .99). Kaplan–Meier survival estimates in both groups were similar (log-rank P = .24), as shown in Figure 2.
      Figure thumbnail gr2
      Figure 2Kaplan–Meier survival estimates by ECMO use as bridge to LTx during the study period. CI, Confidence interval; ECMO, extracorporeal membrane oxygenation.
      Used with permission from Norton Thoracic Institute, Phoenix, Arizona.
      Before 2015, 4 patients had been placed on ECMO at our center between 2011 and 2014. Our ECMO BTT success rate in the historical cohort was 75% (3/4), compared with 100% success rate in the 2015 ECMO BTT cohort. Functional status at listing for LTx was worse in the historical cohort (10 vs 20; P = .03). The 2015 ECMO BTT group had better 1-year survival than the historical BTT cohort (log-rank P = .04).

      Discussion

      From 2011 to 2015, the overall rate of ECMO BTT at our institution was 4.7% (16/334) in our transplant program. This is higher than reported ECMO pretransplant rates from national registry studies, which have been reported to range from 0.6% to 3.5%.
      • George T.J.
      • Beaty C.A.
      • Kilic A.
      • Shah P.D.
      • Merlo C.A.
      • Shah A.S.
      Outcomes and temporal trends among high-risk patients after lung transplantation in the United States.
      • Hayes Jr., D.
      • Tobias J.D.
      • Tumin D.
      Center volume and extracorporeal membrane oxygenation support at lung transplantation in the Lung Allocation Score Era.
      At our center, the use of ECMO as BTT has increased 3-fold from 1.6% (4/241) between 2011 and 2014 to 12.9% (12/93) in 2015. The most likely reason for this upswing—aside from our increase in transplant volume and patients referred in later stages of their fibrotic disease state—is the institution of an intensive ECMO education program and updated technology. Our patients receiving ECMO BTT were younger than patients not receiving BTT, with high acuity (demonstrated by higher LAS and lower functional status at the time of listing). This trend is consistent with reports from UNOS-based studies
      • George T.J.
      • Beaty C.A.
      • Kilic A.
      • Shah P.D.
      • Merlo C.A.
      • Shah A.S.
      Outcomes and temporal trends among high-risk patients after lung transplantation in the United States.
      • Hayes Jr., D.
      • Tobias J.D.
      • Tumin D.
      Center volume and extracorporeal membrane oxygenation support at lung transplantation in the Lung Allocation Score Era.
      • Hayanga A.J.
      • Aboagye J.
      • Esper S.
      • Shigemura N.
      • Bermudez C.A.
      • D'Cunha J.
      • 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.
      and with single-center studies in the United States.
      • Hoopes C.W.
      • Kukreja J.
      • Golden J.
      • Davenport D.L.
      • Diaz-Guzman E.
      • Zwischenberger J.B.
      Extracorporeal membrane oxygenation as a bridge to pulmonary transplantation.
      • Toyoda Y.
      • Bhama J.K.
      • Shigemura N.
      • Zaldonis D.
      • Pilewski J.
      • Crespo M.
      • et al.
      Efficacy of extracorporeal membrane oxygenation as s bridge to lung transplantation.
      Rates of mechanical ventilation pretransplant and CPB use during transplant were higher in the ECMO BTT group, which is consistent with single-center reports from the United States
      • Toyoda Y.
      • Bhama J.K.
      • Shigemura N.
      • Zaldonis D.
      • Pilewski J.
      • Crespo M.
      • et al.
      Efficacy of extracorporeal membrane oxygenation as s bridge to lung transplantation.
      and Europe.
      • Inci I.
      • Klinzing S.
      • Schneiter D.
      • Schuepbach R.A.
      • Kestenholz P.
      • Hillinger S.
      • et al.
      Outcome of extracorporeal membrane oxygenation as a bridge to lung transplantation: an institutional experience and literature review.
      Since the first patient was placed on ECMO at our institution in 2011, practitioners in our program carried out a total of 16 ECMO BTT cannulations by December 2015, with 15 successful “bridges to transplant” (a rate of 93.7%), which is higher than previously reported rates, which range from 46% to 89%,
      • Lang G.
      • Taghavi S.
      • Aigner C.
      • Renyi-Vamos F.
      • Jaksch P.
      • Augustin V.
      • et al.
      Primary lung transplantation after bridge with extracorporeal membrane oxygenation: a plea for a shift in our paradigms for indications.
      • Toyoda Y.
      • Bhama J.K.
      • Shigemura N.
      • Zaldonis D.
      • Pilewski J.
      • Crespo M.
      • et al.
      Efficacy of extracorporeal membrane oxygenation as s bridge to lung transplantation.
      • Shafii A.
      • Mason D.P.
      • Brown C.R.
      • Vakil N.
      • Johnston D.R.
      • Mccurry K.R.
      • et al.
      Growing experience with extracorporeal membrane oxygenation as a bridge to lung transplantation.
      • Javidfar J.
      • Brodie D.
      • Iribarne A.
      • Jurado J.
      • LaVelle M.
      • Brenner K.
      • et al.
      Extracorporeal membrane oxygenation as a bridge to lung transplantation and recovery.
      • Inci I.
      • Klinzing S.
      • Schneiter D.
      • Schuepbach R.A.
      • Kestenholz P.
      • Hillinger S.
      • et al.
      Outcome of extracorporeal membrane oxygenation as a bridge to lung transplantation: an institutional experience and literature review.
      • Tudzinski F.C.
      • Kaestner F.
      • Schafers H.-J.
      • Fandrich S.
      • Seiler F.
      • Bohmer P.
      • et al.
      Outcome of patients with interstitial lung disease treated with extracorporeal membrane oxygenation for acute respiratory failure.
      • Dellgren G.
      • Riise G.C.
      • Sward K.
      • Gilljam M.
      • Rexius H.
      • Liden H.
      • et al.
      Extracorporeal membrane oxygenation as a bridge to lung transplantation: a long term study.
      • Lafarge M.
      • Mordant P.
      • Thabut G.
      • Brouchet L.
      • Falcoz P.-E.
      • Haloun A.
      • et al.
      Experience of extracorporeal membrane oxygenation as a bridge to lung transplantation in France.
      • Anile M.
      • Diso D.
      • Russo E.
      • Patella M.
      • Carillo C.
      • Pecoraro Y.
      • et al.
      Extracorporeal membrane oxygenation as bridge to lung transplantation.
      • Crotti S.
      • Iotti G.A.
      • Lissoni A.
      • Belliato M.
      • Zanierato M.
      • Chierichetti M.
      • et al.
      Organ allocation waiting time during extracorporeal bridge to transplant affects outcomes.
      • Fuehner T.
      • Kuehn C.
      • Hadem J.
      • Wiesner O.
      • Gottlieb J.
      • Tudorache I.
      • et al.
      Extracorporeal membrane oxygenation in awake patients as bridge to lung transplantation.
      • Weig T.
      • Irlbeck M.
      • Frey L.
      • Zwibler B.
      • Winter H.
      • Perissler G.
      • et al.
      Parameters associated with short- and midterm survival in bridging to lung transplantation with extracorporeal membrane oxygenation.
      • Hammainen P.
      • Schersten H.
      • Lemstrom K.
      • Riise G.C.
      • Kukkone S.
      • Sward K.
      • et al.
      Usefulness of extracorporeal membrane oxygenation as a bridge to lung transplantation: a descriptive study.
      as well as 1-year survival of 100%, which is consistent with the range of 62% to 100% reported rates from other single-center studies.
      • Hoopes C.W.
      • Kukreja J.
      • Golden J.
      • Davenport D.L.
      • Diaz-Guzman E.
      • Zwischenberger J.B.
      Extracorporeal membrane oxygenation as a bridge to pulmonary transplantation.
      • Toyoda Y.
      • Bhama J.K.
      • Shigemura N.
      • Zaldonis D.
      • Pilewski J.
      • Crespo M.
      • et al.
      Efficacy of extracorporeal membrane oxygenation as s bridge to lung transplantation.
      • Rehder K.J.
      • Turner D.A.
      • Hartwig M.G.
      • Williford W.L.
      • Bonadonna D.
      • Walczak Jr., R.J.
      • et al.
      Active rehabilitation during extracorporeal membrane oxygenation as a bridge to lung transplantation.
      • Javidfar J.
      • Brodie D.
      • Iribarne A.
      • Jurado J.
      • LaVelle M.
      • Brenner K.
      • et al.
      Extracorporeal membrane oxygenation as a bridge to lung transplantation and recovery.
      • Dellgren G.
      • Riise G.C.
      • Sward K.
      • Gilljam M.
      • Rexius H.
      • Liden H.
      • et al.
      Extracorporeal membrane oxygenation as a bridge to lung transplantation: a long term study.
      • Lafarge M.
      • Mordant P.
      • Thabut G.
      • Brouchet L.
      • Falcoz P.-E.
      • Haloun A.
      • et al.
      Experience of extracorporeal membrane oxygenation as a bridge to lung transplantation in France.
      • Anile M.
      • Diso D.
      • Russo E.
      • Patella M.
      • Carillo C.
      • Pecoraro Y.
      • et al.
      Extracorporeal membrane oxygenation as bridge to lung transplantation.
      • Hammainen P.
      • Schersten H.
      • Lemstrom K.
      • Riise G.C.
      • Kukkone S.
      • Sward K.
      • et al.
      Usefulness of extracorporeal membrane oxygenation as a bridge to lung transplantation: a descriptive study.
      • Mohite P.N.
      • Sabashnikov A.
      • Reed A.
      • Saez D.G.
      • Patil N.P.
      • Popov A.-F.
      • et al.
      Extracorporeal life support in “awake” patients as a bridge to lung transplant.
      The patients who were salvaged using ECMO as BTT all had overall excellent functional status at 1 year, which to date has not been reported in the literature.

       Specialized Extracorporeal Membrane Oxygenation Program

      We have gained valuable experience since our first successful use of ECMO as BTT, and have since refined our clinical practice and decision-making processes. This retrospective review describes our results using ECMO as BTT after implementation of a multidisciplinary ECMO program that uses modern ECMO devices and cannulas. Development of a comprehensive ECMO program is a complex, multifaceted undertaking that requires collaboration from different departments.
      • Hoopes C.W.
      • Kukreja J.
      • Golden J.
      • Davenport D.L.
      • Diaz-Guzman E.
      • Zwischenberger J.B.
      Extracorporeal membrane oxygenation as a bridge to pulmonary transplantation.
      • Hayes Jr., D.
      • Tobias J.D.
      • Tumin D.
      Center volume and extracorporeal membrane oxygenation support at lung transplantation in the Lung Allocation Score Era.
      Successfully restructuring our ECMO program meant upgrading equipment, changing infrastructure, continuously educating our clinicians, and establishing clear and easy communication between bedside staff and physicians. Although it is optimal to place patients who are already on the transplant waitlist on ECMO in the transplant hospital, it is feasible to transport LTx candidates who are already on ECMO should they experience respiratory failure outside the transplant center.
      • Lee S.G.
      • Son B.S.
      • Kang P.J.
      • Cho W.H.
      • Kim D.H.
      • Lee Y.S.
      • et al.
      The feasibility of extracorporeal membrane oxygenation support for inter-hospital transport and as a bridge to lung transplantation.
      One patient in this study (patient 12) was placed on ECMO at a sister facility and was transferred to our center for further management and, ultimately, LTx.

       Length of Stay

      Although the patients in our study experienced good outcomes, ECMO as BTT was associated with longer length of stay and a greater need for rehabilitation. The patients in this study who required ECMO as BTT were more critically ill (confirmed by their higher LAS scores) and were bedbound at the time of ECMO initiation, so prolonged recovery was anticipated. We evaluated each patient's rehabilitation potential before their conditions worsened and necessitated ECMO; however, acuity of illness, ECMO duration, immobility, and sedation all exacerbate the functional decline that affects rehabilitation potential. Fortunately, the waitlist times at our center are relatively short, which helped minimize ECMO duration. This may not be the case in all regions of the country, and other programs should consider patients' expected waitlist time before placing patients on ECMO as BTT.
      • Valapour M.
      • Skeans M.A.
      • Smith J.M.
      • Edwards L.B.
      • Cherikh W.S.
      • Callahan E.R.
      • et al.
      OPTN/SRTR Annual data report 2014: Lung.
      • Crotti S.
      • Iotti G.A.
      • Lissoni A.
      • Belliato M.
      • Zanierato M.
      • Chierichetti M.
      • et al.
      Organ allocation waiting time during extracorporeal bridge to transplant affects outcomes.

       Extracorporeal Membrane Oxygenation–Related Complications

      Delirium is a serious event in critically ill patients that is often associated with pain management and sedation.
      • Reade M.C.
      • Finfer S.
      Sedation and delirium in the intensive care unit.
      We have tried to minimize sedation and to use shorter-acting agents for sedation (eg, propofol or remifentanil), but air hunger and agitation that affect circuit flows and cannula positioning have necessitated sedation for most of our patients. Protocols and guidelines focusing on delirium prevention would likely improve outcomes in our ECMO as BTT cases and is an ongoing effort at our institution. Myopathy has been a major post-transplant complication in the ECMO as BTT group. Factors that may contribute to this morbidity include bedbound status, prolonged hospital stay, and acute exacerbation of disease process, which requires administration of high-dose steroids.
      • Tabarki B.
      • Coffinieres A.
      • Van den Bergh P.
      • Huault G.
      • Landrieu P.
      • Sebire G.
      Critical illness neuromuscular disease: clinical, electrophysiological, and prognostic aspects.
      Myopathy will likely remain a problem in these patients, but active engagement of each patient in physical therapy and ambulation (if possible) may help lessen the degree of critical illness myopathy. Earlier institution of ECMO (ie, before patients have critically deteriorated) may facilitate ambulation in these patients.
      • Rehder K.J.
      • Turner D.A.
      • Hartwig M.G.
      • Williford W.L.
      • Bonadonna D.
      • Walczak Jr., R.J.
      • et al.
      Active rehabilitation during extracorporeal membrane oxygenation as a bridge to lung transplantation.
      We are in the process of educating our intensive care unit personnel and ancillary staff on the importance and feasibility of ambulation while on ECMO. In the meantime, our center continues to aggressively recruit donor lungs to expand the organ pool, decreases postoperative ventilator times with scheduled bronchoscopy, and refers patients to acute rehabilitation after discharge for conditioning exercises.
      In an effort to encourage active participation in physical therapy, we avoid femoral cannulation unless it must be used on an emergency basis. Stable patients are taken to the operating room, where VV ECMO is deployed using both fluoroscopy and transesophageal echocardiography with a dual-lumen internal jugular cannula. Tracheostomy can facilitate ventilator weaning and patient activity,
      • Rehder K.J.
      • Turner D.A.
      • Hartwig M.G.
      • Williford W.L.
      • Bonadonna D.
      • Walczak Jr., R.J.
      • et al.
      Active rehabilitation during extracorporeal membrane oxygenation as a bridge to lung transplantation.
      and was performed in 7 of 12 of our ECMO cases at the time of ECMO initiation with no tracheostomy-related complications. Emergency cannulation at the bedside using the internal jugular vein as inflow and the femoral vein as outflow can be performed in patients who cannot tolerate transport to the operating room.
      Because of the greater need for blood transfusion during and after transplant and the higher rates of thrombosis associated with ECMO, we continue to modify our ECMO coagulation management. Hemostasis management encompasses the traditional coagulation markers, but attention to D-dimer, AT, Protein C, and Protein S are particularly important. D-dimer evaluation can detect clot degradation, fibrin split products, and reduction of clot stability. AT, Protein C, and Protein S are natural anticoagulants, but deficiency of any of these could promote a procoagulant state. Pulmonary embolus and DVT continue to be postoperative concerns, especially because steroid use and perioperative immobility increase the risk of thrombosis. DVT prophylaxis in the perioperative period remains very important. We were able to decannulate all patients after the transplant procedure in the operating room, which allowed for reversal of anticoagulation and minimized further bleeding risk postimplantation. Some centers have reported the use of ECMO post-transplant to treat primary graft dysfunction or pulmonary hypertension,
      • Fischer S.
      • Bohn D.
      • Rycus P.
      • Pierre A.F.
      • de Perrot M.
      • Waddell T.K.
      • et al.
      Extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: analysis of the Extracorporeal Life Support Organization (ELSO) registry.
      • Pereszlenyi A.
      • Lang G.
      • Steltzer H.
      • Hetz H.
      • Kocher A.
      • Neuhauser P.
      • et al.
      Bilateral lung transplantation with intra- and postoperatively prolonged ECMO support in patients with pulmonary hypertension.
      but this was not necessary for any of the patients in our cohort.

       Other Considerations

      No difference was observed in rates of grade 3 primary graft dysfunction at 48 to 72 hours of transplant between ECMO BTT and non-BTT groups. Although this is consistent with rates reported by the Lung Transplant Outcomes Group,
      • Fischer S.
      • Bohn D.
      • Rycus P.
      • Pierre A.F.
      • de Perrot M.
      • Waddell T.K.
      • et al.
      Extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: analysis of the Extracorporeal Life Support Organization (ELSO) registry.
      the true effect of ECMO as BTT on development of chronic rejection has not yet been studied. We will continue to monitor the patients we treated with ECMO as BTT for long-term survival and incidence of chronic allograft dysfunction, and intend to report those findings at a later date.

       Study Limitations

      This study is subject to the limitations associated with any retrospective, single-center review. Because of the relatively small numbers in our sample, our data lack statistical power to conduct a meaningful multivariable analysis adjusting for differences in baseline characteristics including higher acuity of our ECMO BTT group, whether patients were ventilated at the time of listing, and disposition at discharge compared with the non-BTT group. Consequently, the stand-alone effect of ECMO as BTT on LTx outcomes or the impact of various known risk factors (eg, higher LAS or greater patient age) is difficult to ascertain from our existing data. Long-term outcomes in both groups are lacking, although they are being prospectively studied. There is a need for further prospective, multicenter studies that would assess the effects of ECMO use pretransplant.

      Conclusions

      Our success with ECMO as BTT is similar to reports from other centers,
      • Hoopes C.W.
      • Kukreja J.
      • Golden J.
      • Davenport D.L.
      • Diaz-Guzman E.
      • Zwischenberger J.B.
      Extracorporeal membrane oxygenation as a bridge to pulmonary transplantation.
      • Toyoda Y.
      • Bhama J.K.
      • Shigemura N.
      • Zaldonis D.
      • Pilewski J.
      • Crespo M.
      • et al.
      Efficacy of extracorporeal membrane oxygenation as s bridge to lung transplantation.
      and reported outcomes of those with ECMO BTT who undergo LTx at high-volume centers have been comparable to those who undergo non-BTT LTx.
      • Hayes Jr., D.
      • Tobias J.D.
      • Tumin D.
      Center volume and extracorporeal membrane oxygenation support at lung transplantation in the Lung Allocation Score Era.
      • Hayanga A.J.
      • Aboagye J.
      • Esper S.
      • Shigemura N.
      • Bermudez C.A.
      • D'Cunha J.
      • 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.
      Our positive outcomes were due in large part to the education of our staff on the ECMO devices and processes, improved clinical infrastructure surrounding ECMO use, and upgraded models of ECMO machines. Our study adds to the literature because it illustrates what can be accomplished through a dedicated ECMO program, and because the 1-year functional status of patients bridged to transplant with ECMO is rarely reported.
      The use of ECMO as BTT needs to be better defined as a part of the global algorithm in the care of patients with end-stage lung disease. Myopathy and delirium remain serious complications at our center, and more attention to ECMO timing and duration, sedation, and steroid doses may be warranted. Other complications, such as DVTs and bleeding, may be remedied by upgrading of our coagulation instrumentation to the thromboelastogram to allow faster evaluation of coagulopathy. Further evaluation and study of the coagulation panel in the post-ECMO/post-transplant phase may offer more insight into the high number of thrombotic complications, although this seems to be a problem commonly seen at other centers. Although no excessive severe primary graft dysfunction was evident in this patient cohort, it remains to be seen whether rejection, incidence of bronchiolitis obliterans syndrome, and overall survival are affected in patients who receive ECMO as BTT in the new era.

       Conflict of Interest Statement

      Authors have nothing to disclose with regard to commercial support.
      The authors thank Clare Prendergast, who provided editorial assistance for this article.

      Supplementary Data

      References

        • George T.J.
        • Beaty C.A.
        • Kilic A.
        • Shah P.D.
        • Merlo C.A.
        • Shah A.S.
        Outcomes and temporal trends among high-risk patients after lung transplantation in the United States.
        J Heart Lung Transplant. 2012; 31: 1182-1191
        • Yusen R.D.
        • Edwards L.B.
        • Kucheryavaya A.Y.
        • Benden C.
        • Dipchand A.I.
        • Dobbels F.
        • et al.
        The Registry of the International Society for Heart and Lung Transplantation: Thirty-First Adult Lung and Heart-Lung Transplant Report-2015; Focus Theme: Early Graft Failure.
        J Heart Lung Transplant. 2015; 34: 1264-1277
        • Singer J.P.
        • Blanc P.D.
        • Hoopes C.
        • Golden J.A.
        • Koff J.L.
        • Leard L.E.
        • et al.
        The impact of pre-transplant mechanical ventilation on short- and long-term survival after lung transplantation.
        Am J Transplant. 2011; 11: 2197-2204
        • Gottlieb J.
        • Warnecke G.
        • Hadem J.
        • Dierich M.
        • Wiesner O.
        • Fühner T.
        • et al.
        Outcome of critically ill lung transplant candidates on invasive respiratory support.
        Intensive Care Med. 2012; 38: 968-975
        • Lang G.
        • Taghavi S.
        • Aigner C.
        • Renyi-Vamos F.
        • Jaksch P.
        • Augustin V.
        • et al.
        Primary lung transplantation after bridge with extracorporeal membrane oxygenation: a plea for a shift in our paradigms for indications.
        Transplantation. 2012; 93: 729-736
        • Hoopes C.W.
        • Kukreja J.
        • Golden J.
        • Davenport D.L.
        • Diaz-Guzman E.
        • Zwischenberger J.B.
        Extracorporeal membrane oxygenation as a bridge to pulmonary transplantation.
        J Thorac Cardiovasc Surg. 2013; 145: 862-868
        • Toyoda Y.
        • Bhama J.K.
        • Shigemura N.
        • Zaldonis D.
        • Pilewski J.
        • Crespo M.
        • et al.
        Efficacy of extracorporeal membrane oxygenation as s bridge to lung transplantation.
        J Thorac Cardiovasc Surg. 2013; 145: 1065-1071
        • Rehder K.J.
        • Turner D.A.
        • Hartwig M.G.
        • Williford W.L.
        • Bonadonna D.
        • Walczak Jr., R.J.
        • et al.
        Active rehabilitation during extracorporeal membrane oxygenation as a bridge to lung transplantation.
        Respir Care. 2013; 58: 1291-1298
        • Shafii A.
        • Mason D.P.
        • Brown C.R.
        • Vakil N.
        • Johnston D.R.
        • Mccurry K.R.
        • et al.
        Growing experience with extracorporeal membrane oxygenation as a bridge to lung transplantation.
        ASAIO J. 2012; 8: 526-529
        • Javidfar J.
        • Brodie D.
        • Iribarne A.
        • Jurado J.
        • LaVelle M.
        • Brenner K.
        • et al.
        Extracorporeal membrane oxygenation as a bridge to lung transplantation and recovery.
        J Thorac Cardiovasc Surg. 2012; 144: 716-721
        • Abrams D.
        • Javidfar J.
        • Farrand E.
        • Mongero L.B.
        • Agerstrand C.L.
        • Ryan P.
        • et al.
        Early mobilization of patients receiving extracorporeal membrane oxygenation: a retrospective cohort study.
        Crit Care. 2014; 18: R38
        • Inci I.
        • Klinzing S.
        • Schneiter D.
        • Schuepbach R.A.
        • Kestenholz P.
        • Hillinger S.
        • et al.
        Outcome of extracorporeal membrane oxygenation as a bridge to lung transplantation: an institutional experience and literature review.
        Transplantation. 2015; 99: 1667-1671
        • Mason D.P.
        • Thuita L.
        • Nowicki E.R.
        • Murthy S.C.
        • Pettersson G.B.
        • Blackstone E.H.
        Should lung transplantation be performed for patients on mechanical respiratory support? The US experience.
        J Thorac Cardiovasc Surg. 2010; 139: 765-773
        • Hayes Jr., D.
        • Tobias J.D.
        • Tumin D.
        Center volume and extracorporeal membrane oxygenation support at lung transplantation in the Lung Allocation Score Era.
        Am J Respir Crit Care Med. 2016; 194: 317-326
        • Hayanga A.J.
        • Aboagye J.
        • Esper S.
        • Shigemura N.
        • Bermudez C.A.
        • D'Cunha J.
        • 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: 291-296
        • Iribarne A.
        • Russo M.J.
        • Davies R.R.
        • Hong K.N.
        • Gelijns A.C.
        • Bacchetta M.D.
        • et al.
        Despite decreased wait-list times for lung transplantation, lung allocation scores continue to increase.
        Chest. 2009; 135: 923-928
        • Valapour M.
        • Skeans M.A.
        • Smith J.M.
        • Edwards L.B.
        • Cherikh W.S.
        • Callahan E.R.
        • et al.
        OPTN/SRTR Annual data report 2014: Lung.
        Am J Transplant. 2016; 16: 141-168
        • Tabarki B.
        • Coffinieres A.
        • Van den Bergh P.
        • Huault G.
        • Landrieu P.
        • Sebire G.
        Critical illness neuromuscular disease: clinical, electrophysiological, and prognostic aspects.
        Arch Dis Child. 2002; 86: 103-107
      1. Policy 10 Allocation of Lungs. Organ Procurement and transplantation network (OPTN) policies. Available at: https://optn.transplant.hrsa.gov/media/1200/optn_policies.pdf#nameddest=Policy_10. Accessed September 1, 2016.

        • Tudzinski F.C.
        • Kaestner F.
        • Schafers H.-J.
        • Fandrich S.
        • Seiler F.
        • Bohmer P.
        • et al.
        Outcome of patients with interstitial lung disease treated with extracorporeal membrane oxygenation for acute respiratory failure.
        Am J Respir Crit Care Med. 2016; 193: 527-533
        • Dellgren G.
        • Riise G.C.
        • Sward K.
        • Gilljam M.
        • Rexius H.
        • Liden H.
        • et al.
        Extracorporeal membrane oxygenation as a bridge to lung transplantation: a long term study.
        Eur J Cardiothorac Surg. 2015; 47: 95-100
        • Lafarge M.
        • Mordant P.
        • Thabut G.
        • Brouchet L.
        • Falcoz P.-E.
        • Haloun A.
        • et al.
        Experience of extracorporeal membrane oxygenation as a bridge to lung transplantation in France.
        J Heart Lung Transplant. 2013; 32: 905-913
        • Anile M.
        • Diso D.
        • Russo E.
        • Patella M.
        • Carillo C.
        • Pecoraro Y.
        • et al.
        Extracorporeal membrane oxygenation as bridge to lung transplantation.
        Transplant Proc. 2013; 45: 2621-2623
        • Crotti S.
        • Iotti G.A.
        • Lissoni A.
        • Belliato M.
        • Zanierato M.
        • Chierichetti M.
        • et al.
        Organ allocation waiting time during extracorporeal bridge to transplant affects outcomes.
        Chest. 2013; 144: 1018-1025
        • Fuehner T.
        • Kuehn C.
        • Hadem J.
        • Wiesner O.
        • Gottlieb J.
        • Tudorache I.
        • et al.
        Extracorporeal membrane oxygenation in awake patients as bridge to lung transplantation.
        Am J Respir Crit Care Med. 2012; 185: 763-768
        • Weig T.
        • Irlbeck M.
        • Frey L.
        • Zwibler B.
        • Winter H.
        • Perissler G.
        • et al.
        Parameters associated with short- and midterm survival in bridging to lung transplantation with extracorporeal membrane oxygenation.
        Clin Transplant. 2013; 27: E563-E570
        • Hammainen P.
        • Schersten H.
        • Lemstrom K.
        • Riise G.C.
        • Kukkone S.
        • Sward K.
        • et al.
        Usefulness of extracorporeal membrane oxygenation as a bridge to lung transplantation: a descriptive study.
        J Heart Lung Transplant. 2011; 30: 103-107
        • Mohite P.N.
        • Sabashnikov A.
        • Reed A.
        • Saez D.G.
        • Patil N.P.
        • Popov A.-F.
        • et al.
        Extracorporeal life support in “awake” patients as a bridge to lung transplant.
        J Thorac Cardiovasc Surg. 2015; 63: 699-705
        • Lee S.G.
        • Son B.S.
        • Kang P.J.
        • Cho W.H.
        • Kim D.H.
        • Lee Y.S.
        • et al.
        The feasibility of extracorporeal membrane oxygenation support for inter-hospital transport and as a bridge to lung transplantation.
        Ann Thorac Cardiovasc Surg. 2014; 20: 26-31
        • Reade M.C.
        • Finfer S.
        Sedation and delirium in the intensive care unit.
        N Engl J Med. 2014; 370: 444-454
        • Fischer S.
        • Bohn D.
        • Rycus P.
        • Pierre A.F.
        • de Perrot M.
        • Waddell T.K.
        • et al.
        Extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: analysis of the Extracorporeal Life Support Organization (ELSO) registry.
        J Heart Lung Transplant. 2007; 26: 472-477
        • Pereszlenyi A.
        • Lang G.
        • Steltzer H.
        • Hetz H.
        • Kocher A.
        • Neuhauser P.
        • et al.
        Bilateral lung transplantation with intra- and postoperatively prolonged ECMO support in patients with pulmonary hypertension.
        Eur J Cardiothorac Surg. 2002; 21: 858-863