Outcomes of Intraoperative Venoarterial Extracorporeal Membrane Oxygenation Versus Cardiopulmonary Bypass During Lung Transplantation

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Outcomes of Intraoperative Venoarterial Extracorporeal Membrane Oxygenation Versus Cardiopulmonary Bypass During Lung Transplantation Christian A. Bermudez, MD, Akira Shiose, MD, Stephen A. Esper, MD, Norihisa Shigemura, MD, PhD, Jonathan D’Cunha, MD, PhD, Jay K. Bhama, MD, Thomas J. Richards, PhD, Peter Arlia, CP, Maria M. Crespo, MD, and Joseph M. Pilewski, MD Department of Cardiothoracic Surgery, Department of Anesthesiology, and Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania

Background. The intraoperative use of cardiopulmonary bypass (CPB) in lung transplantation has been associated with increased rates of pulmonary dysfunction and bleeding complications. More recently, extracorporeal membrane oxygenation (ECMO) has emerged as a valid alternative method of support and has been our preferred method of support since March 2012. We compared early and midterm outcomes of these 2 support methods. Methods. Between July 2007 and April 2013, 271 consecutive patients underwent lung transplant using CPB (n [ 222) or ECMO (n [ 49). We retrospectively reviewed the outcomes of these patients requiring CPB or ECMO during lung transplant. Results. The CPB and ECMO groups had comparable demographic and operative characteristics; however, the ECMO group had higher mean lung allocation scores (73 vs 52, p < 0.001). In the CPB group, more patients required reintubation (35.6% vs 20.4%, p [ 0.04) or

temporary tracheostomy (44.6% vs 28.6%, p [ 0.05). Patients in the CPB group had a higher rate of renal failure requiring dialysis than the ECMO group (22.1% vs 8.2 %, p [ 0.028). There were no differences in severe PGD requiring postoperative circulatory support (p [ 0.83) or the need for perioperative red blood cell transfusions (p [ 0.64) between the groups. No differences in 30-day (5% CPB vs 4.1% ECMO) or 6-month mortality (14.4% CPB vs 14.3% ECMO) were noted. Conclusions. The use of ECMO in lung transplant is safe and in our experience was associated with decreased rates of pulmonary and renal complications, as compared with CPB. Extracorporeal membrane oxygenation has become our preferred method of intraoperative support during lung transplantation.

L

support during LT [1]. Although CPB provides adequate conditions to successfully complete a high-risk LT, CPB use significantly activates coagulation and inflammatory cascades and requires high-dose anticoagulation due to the number of blood-activating surfaces, including plastic tubing, a reservoir, and suction lines. For these reasons, CPB is associated with higher risk of bleeding, PGD, and other pulmonary complications as compared with LT performed without the use of CPB [2–4]. Extracorporeal membrane oxygenation (ECMO) uses a low-profile centrifugal pump and a membrane oxygenator in a closed, more limited circuit. ECMO was initially used in pediatric patients and in cases of profound acute lung injury. Improvements in the ECMO technology and experience gained more recently with ECMO use in patients with PGD (post-LT) [5] and with ECMO as a bridge to LT [6, 7] have stimulated ECMO use as a method of intraoperative support. Using ECMO for intraoperative circulatory support has the potential to decrease bleeding complications (due to lower heparin doses), PGD, and other complications associated with the activation of

ung transplantation (LT) is considered a valid therapeutic option in the treatment of advanced end-stage lung disease. Important advances have been made in the perioperative management of the patients undergoing LT with improved outcomes and acceptable rates of primary graft dysfunction (PGD) and postoperative complications. Although LT is frequently performed off-pump, circulatory support is necessary in 30% to 40% of patients who undergo LT [1]. Pulmonary support is most frequently necessary in recipients with significant pulmonary hypertension, right ventricular dysfunction, or who are unable to tolerate single-lung ventilation during LT, all frequent signs of advanced, end-stage lung disease. Cardiopulmonary bypass (CPB) has been historically considered the standard method of intraoperative Accepted for publication June 30, 2014. Presented at the Fiftieth Annual Meeting of The Society of Thoracic Surgeons, Orlando, FL, Jan 25–29, 2014. Address correspondence to Dr Bermudez, UPMC Presbyterian, Ste C-920, 200 Lothrop St, Pittsburgh, PA 15213; e-mail: [email protected].

Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier

(Ann Thorac Surg 2014;98:1936–43) Ó 2014 by The Society of Thoracic Surgeons

0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.06.072

blood components and inflammation. Furthermore, intraoperative ECMO allows the continuation of support using the same system in cases of severe PGD. In this study we compared early outcomes of LT using these 2 methods of intraoperative support.

Patients and Methods Study Protocol We performed a retrospective analysis of patients requiring intraoperative mechanical support during LT. Between July 2007 and April 2013, 647 consecutive patients underwent primary LT in our institution. Of these, 374 patients (58%) were performed off-pump and 273 (42%) required the use of intraoperative mechanical support, including 222 patients who received CPB support, 49 patients who were supported with ECMO, and 2 patients requiring combined CPB and ECMO support. Consistent with current usage in the fields of pulmonary and circulatory support, we use the term ECMO to describe a limited bypass system utilizing an oxygenator and limited tubing that avoids the use of a reservoir with stagnant blood. Since March 2012, ECMO has been our preferred method of support with only 2 patients requiring CPB. These 2 patients began LT on ECMO, were switched to CPB due to uncontrolled bleeding, and were excluded from this study. Redo LTs (20 patients) during the same period were also excluded. Data were obtained from the University of Pittsburgh Medical Center transplant database and patients’ charts. This study was approved by the Institutional Review Board and the informed consent requirement was waived.

Patients and Support Selection Intraoperative mechanical support is routinely considered at our center in patients with severe pulmonary hypertension (transpulmonary pressure gradient > 20 mm Hg), the inability to tolerate single-lung ventilation, hemodynamic derangement after pulmonary artery clamping, or who require associated cardiac procedures. More recently we have considered intraoperative mechanical support during lobar lung transplant to prevent hyperperfusion of the reduced size allograft. Historically, we used CPB in all patients undergoing LT, necessitating intraoperative support. Beginning in 2008, as we observed an increasing number of patients supported preoperatively with ECMO before undergoing LT (ECMO bridge), we considered the continuation of the same support during the intraoperative procedure. Venoarterial (VA) ECMO was maintained during the LT surgery or venovenous (VV) ECMO was converted to VA ECMO to simplify the surgical approach, especially in cases when ECMO support was considered to be extended postoperatively. Since March 2012, ECMO has become our preferred method of support and we utilize CPB only in patients needing combined cardiac interventions or in cases of severe, uncontrolled intraoperative bleeding or severe hemodynamic instability. We favor VA ECMO over VV ECMO due to the inability

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to maintain adequate flow with VV ECMO during hilar exposure due to atrial compression. During the study period there were no changes in donor organ management. No ex vivo preservation techniques were used in these cases. There were also no differences in patient management or immunosuppression strategy, which comprised standard induction and maintenance therapy based on triple-drug regimen, during the study period.

Extracorporeal Membrane Oxygenation and Cardiopulmonary Bypass Implantation The bilateral anteroaxillary thoracotomy has been our preferred surgical approach in double LT. We reserve the clamshell incision to cases with inadequate exposure (severely retracted chest cavity or obesity), increased technical difficulty (multiple thoracotomies or redo LT), or when it is the surgeon’s preference. In the absence of femoral artery calcifications or disease, peripheral cannulation using right femoral vein and artery has been favored in the cases with the minimally invasive approach of using a limited anteroaxillary thoracotomy. Central cannulation in the ascending aorta and right atrium is used in cases with standard clamshell incision or peripheral vascular disease. In patients with preoperative peripheral ECMO as a bridge to LT, maintenance of preoperative cannulation was attempted. Initially, we converted to full CPB; more recently, we have been converting to VA ECMO. After entering the chest cavity and prior to cannulation, heparinization was used in both groups. In the CPB group, 300 IU heparin/kg was administered to maintain an activated clotting time greater than 400 seconds during bypass. After discontinuation of CPB, protamine was used to reverse the heparin effect. In the ECMO group, an initial bolus of 5,000 IU heparin was given to maintain an activated clotting time 180 to 250 seconds during support. In the ECMO group, protamine administration to revert the heparin effect was only considered after decannulation in cases of significant clinical bleeding manifestations. The CPB system used included a St€ ockert SIII or S5 (Sorin Group GMBH, Munich, Germany) heart and lung machine and roller pump, Terumo Xcoating tubing, Capiox adult hardshell venous reservoir with Xcoating (Terumo CV Corp, Elkton, MD), Capiox RX 2.5 with Xcoating, a hollow fiber oxygenator, and a Capiox adult arterial filter with Xcoating. The ECMO system that we used from July 2007 until March 2012 included CarmedaBioActive surface (Medtronic Inc, Minneapolis, MN) tubing, a BPX-80 centrifugal pump with Carmeda BioActive surface, and a Quadrox i-D oxygenator with Bioline Coating (Maquet Cardiopulmonary AG, Rastatt, Germany). In March 2012, an integrated, hybrid, convertible ECMO and CPB system was implemented using Carmeda tubing, with an Affinity NT adult Carmeda oxygenator (Medtronic Inc), an Affinity NT hardshell cardiotomy reservoir with trillium coating (Medtronic Inc), an Affinity AF1000 arterial filter with balance coating (Medtronic Inc), and a Revolution

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centrifugal blood pump-PC coated (Sorin Group Italia, Mirandola, Italy). The pump setup was on a St€ ockert SIII (Sorin Group GMBH) heart and lung machine. The venous reservoir and arterial filter were added in parallel but were excluded during the operation unless emergent implementation of CPB was needed. If CPB was required, full heparinization was provided before initiation of CPB. In case of peripheral cannulation, 15F to 19F BioMedicus arterial cannulas with Carmeda BioActive surface and 25F to 29F Bio-Medicus venous cannulas with Carmeda BioActive surface were inserted using an open technique, under direct visualization. Adequate perfusion of lower extremities during the case was monitored using the Somanetics Invos oximeter (Covidien, Mansfield, MA). In patients with evidence of leg ischemia, an additional 8F Bio-Medicus cannula with Carmeda BioActive surface was inserted more distal in the femoral artery to obtain distal perfusion.

Data Analysis Continuous variables are shown as mean
SD or median (range). Actuarial survival estimates were calculated using Kaplan-Meier life table analysis. The log-rank statistic was used to determine whether the survival curves differed, with a p value less than 0.05 considered statistically significant. Statistical analysis was performed using STATA version 8.2 (STATA Corp, College Station, TX).

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49 patients in the ECMO group (42.8%) (p < 0.01). The ECMO group also had higher mean lung allocation score than the CPB group. There were no differences between the 2 groups with regard to the surgical approach (p ¼ 0.21). Double LT was used preferentially over single LT in both groups. The ECMO group had a significantly higher rate of the double lobar LT modification, which was used in 12 (24.5%) patients in the ECMO group versus 19 (8.6 %) in the CPB group (p < 0.01) (Table 2). The CPB group contained all the patients who underwent cardiac procedures at the time of LT. All of the patients who required a concomitant cardiac procedure were clinically stable, and were not on preoperative ECMO or mechanical ventilation prior to transplant (Table 2). The combined allograft ischemic time was comparable in both groups (p ¼ 0.29). The time on support was significantly longer in the ECMO group than in the CPB group (p < 0.01) (Table 2). Patients in the ECMO group required significantly more intraoperative red blood cell (RBC) transfusion than the CPB group (7.7 units vs 5.9 units, p ¼ 0.02) (Table 3). However, there were no differences between the groups in the overall transfusion requirements during the perioperative period (72 hours) with respect to transfusion of either packed RBCs (p ¼ 0.64) or plasma (fresh frozen plasma) (p ¼ 0.17) (Table 3). There was a trend toward lower platelet concentrate transfusion in the ECMO group (4U vs 8U, p ¼ 0.08).

Postoperative Course

Results Demographic and Operative Data The CPB and ECMO groups had similar demographic characteristics including age, gender, and diagnosis (Table 1). A significant difference was noted in the use of preoperative ECMO as a bridge to LT, which was used in only 16 of 222 patients in the CPB group (7.2%), but 21 of

Although no difference in initial hours on mechanical ventilation was noted between the groups, more patients in the CPB group required re-intubation (35.6% vs 20.4%, p ¼ 0.04) or temporary tracheostomy (44.6% vs 28.6%, p ¼ 0.05) (Table 4). Additionally, there was a trend toward longer total mechanical ventilation time in the CPB group as compared with the ECMO group (p ¼ 0.06) (Table 4).

Table 1. Patient Demographics

Characteristic Age at transplant (years) (mean
SD) Sex, n (%) Male Female Diagnosis, n (%) IPF COPD Bronchiectasis/CF PPH Other Preoperative ECMO (bridge), n (%) LAS at transplant (mean
SD) a

CPB (n ¼ 222)

ECMO (n ¼ 49)

54.4
14.1

50.3
15.0

130 (58.6%) 92 (41.4%)

27 (55.1%) 22 (44.9%)

83 (37.4%) 46 (20.7%) 30 (13.5%) 10 (4.5%) 53 (12.6%) 16 (7.2%) 52.9
20.2

23 (46.9%) 4 (8.2%) 10 (20.4%) 0 (0%) 12 (6.1%) 21 (42.8%) 73.3
22.0

p Value (CPB vs ECMO) 0.08 0.75

Off-Pump (n ¼374)

p Value (3 Groups)

59.3
13.2

0.04 0.91

215 (57.5%) 159 (42.5%) <0.01a

0.08

<0.01 <0.01

122 (32.6%) 178 (47.6%) 45 (12.0%) 0 (0%) 29 (7.8%) 0 (0%) 41.8
13.5

<0.01 <0.01

Off-pump group had significantly more patients with COPD than ECMO or CPB group.

CF ¼ cystic fibrosis; COPD ¼ chronic obstructive pulmonary disease; CPB ¼ cardiopulmonary bypass; ECMO ¼ extracorporeal membrane oxygenation; IPF ¼ idiopathic pulmonary fibrosis; LAS ¼ lung allocation score; PPH ¼ primary pulmonary hypertension.

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Table 2. Operative Data

Characteristic Approach, n (%) Anteroaxillary/ Anterolateral Clamshell Median sternotomy Transplant type, n (%) Double Single Lobar transplant, n (%) Associated cardiac procedures, n (%) CABG AVR TV repair PFO/ASD repair Other Ischemic time (minutes, mean
SD) Time of support, minutes Mean
SD Median (range)

CPB (n ¼ 222)

ECMO (n ¼ 49)

163 (73.5%) 55 (24.8%) 4 (1.8)

42 (85.7%) 7 (14.3%) 0 (0.0%)

p Value (CPB vs ECMO)

355 (94.9%) 18 (4.8%) 1 (0.3%)

(96.4%) (3.6%) (8.6%) (24.5%) 6 2 10 34 2 363.2
75.5

49 (100%) 0 12 (24.5%) 0 (0.0%)

375.2
66.1

232.5
88.6 242 (15–576)

366.6
144.0 327 (113–717)

<0.01 <0.01

0.29 <0.01

There was also a trend toward shorter mean intensive care unit (ICU) stay in the ECMO group compared with the CPB group (p ¼ 0.06) (Table 4). No differences in total hospital length of stay were noted (Table 4). Patients in the CPB group had higher rate of renal failure requiring dialysis than in the ECMO group (22.1% vs 8.2%, p ¼ 0.028). There were no differences between the 2 groups regarding other complications, including cerebrovascular accidents and atrial fibrillation (Table 5). There were no significant differences in the number of patients requiring prolonged postoperative ECMO (> 24 hours) for PGD. Prolonged postoperative ECMO was required in 34 of 222 patients (15.3%) in the CPB group and 9 of 49 patients (18.3 %) in the ECMO group (p ¼ 0.83). Six additional patients in the ECMO group Table 3. Intraoperative and Perioperative Transfusions ECMO (n ¼ 49)

Intraoperative RBC 5.9
4.5 7.7
5.2 FFP 3.1
3.8 3.0
3.9 Platelets 8.0
0.7 4.0
1.0 Total perioperative (72 hours) RBC 14.9
14.1 13.1
13.4 FFP 9.3
14.0 8.4
15.1 Platelets 11.0
14.3 10.7
20.5

p Value 0.02 0.85 0.08 0.64 0.17 0.08

CPB ¼ cardiopulmonary bypass; ECMO ¼ extracorporeal membrane oxygenation; FFP ¼ fresh frozen plasma; RBC ¼ red blood cells.

281 93 5 0

(75.1%) (24.9%) (1.39%) (0.0%)

321.4
68.7

< 0.01b < 0.01

< 0.01 N/A

N/A N/A b

The off-pump group had more lobar lung transplants

ASD ¼ atrial septal defect; AVR ¼ aortic valve replacement; CABG ¼ coronary artery bypass grafting; ECMO ¼ extracorporeal membrane oxygenation; N/A ¼ not applicable; PFO ¼ patent foramen ovale;

CPB (n ¼ 222)

< 0.01a

0.36 214 8 19 54

p Value (3 groups) < 0.01

0.21

a Off-pump group had significantly more single lung transplants than ECMO or CPB group. than the CPB or ECMO group.

Transfusion Requirements (Units Transfused
SD)

Off-Pump (n¼374)

CPB ¼ cardiopulmonary bypass; TV ¼ tricuspid valve.

were maintained electively on postoperative ECMO (with no weaning attempt) because they were considered to be at high risk for PGD due to the presence of preoperative ECMO as a bridge to LT. This has been our programmatic approach for ECMO bridge cases since January 2013. These patients were decannulated electively in the ICU in less than 24 hours after transplantation.

Survival There were no differences in 30-day, 6-month, or 1-year mortality between the groups (Table 5). The causes of early and late mortality also did not differ between the 2 groups (Table 6). Unadjusted survival was examined after transplantation in the CPB and ECMO groups and compared with survival in patients with the LT performed off-pump (Fig 1). There were no significant differences in overall survival (p ¼ 0.21).

Comment Although some controversy still exists [1, 8] regarding the potentially deleterious effect of CPB on newly implanted lung allografts, there is important evidence associating CPB use with increased PGD, prolonged mechanical ventilation, a higher rate of bleeding complications and transfusions, and an increased rate of neurologic complications [1–4, 9]. The large bloodactivating surfaces present in the CPB tubing, venous reservoir, oxygenator, and cardiotomy suction have been associated clinically and experimentally with profound

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Table 4. Postoperative Course

Variable Mechanical ventilation, initial (hours, mean
SD) Reintubation n (%) Mechanical ventilation, total (hours) Mean
SD Median (range) Tracheostomy n (%) ICU LOS (days, mean
SD) Hospital LOS (days) Median (95% CI) Mean
SD a

CPB (n ¼ 222)

ECMO (n ¼ 49)

p Value (CPB vs ECMO)

Off-Pump (n ¼ 374)

p Value (3 Groups)

226.0
306.6

184.7
223.1

0.94

43.9
77.9

< 0.01

80 (36.0%)

10 (20.4%)

0.04 0.06

105 (28.1%)

< 0.01a < 0.01

380.2
654.8 150 (8, 5360) 99 (44.6%) 21.9
31.3

250.3
393.4 130 (11, 2343) 14 (28.6%) 15.1
20.5

43 (38–49) 52
47.2

41 (32–53) 49
44.3

0.05 0.06

141.6
342.1 31.5 (6, 372) 61 (16.3%) 10.4
17.6

< 0.01 < 0.01

0.37 0.55

24 (22–27) 30.9
24.2

< 0.01 < 0.01

More patients in the CPB group required reintubation than in the ECMO or off-pump group.

CI ¼ confidence interval; LOS ¼ length of stay.

CPB ¼ cardiopulmonary bypass;

ECMO ¼ extracorporeal membrane oxygenation;

activation of the coagulation cascade and inflammatory system [10]. In addition, CPB use requires high doses of intravenous heparin to prevent thromboembolism. For these reasons, alternative methods of support have been explored to minimize potential complications. ECMO utilizes a closed circuit, and no venous reservoir or additional cardiotomy suction is utilized. Newer ECMO systems are available with heparin-coated and polymercoated centrifugal pumps and oxygenators and have improved biocompatibility allowing ECMO utilization for prolonged periods of time before or after LT, with only limited metabolic derangement [11]. Recent reports from active LT and ECMO centers have suggested the potential benefit of the use of ECMO over CPB in LT. Ius and colleagues [12] found a significant mortality reduction with ECMO as compared with CPB (13% vs 39%) and lower rates of PGD and renal failure

ICU ¼ intensive care unit;

requiring dialysis. Aigner and colleagues [13] suggested that ECMO can be utilized with results that are at least comparable with CPB, and ECMO’s versatility allowed them to simplify the management of complex patients by maintaining the same system utilized intraoperatively in the postoperative period. We previously published our experience at the University of Pittsburgh with the use of ECMO in PGD and ECMO as bridge to LT with encouraging results [5–7]. We decided to extend the use of ECMO intraoperatively based on the experience we had gained and the increasing complexity of patients who undergo LT, with higher rates of postoperative ECMO support especially in patients with ECMO as a bridge to LT. In this study we review our early experience with intraoperative ECMO in patients undergoing primary LT. Because our first experiences with intraoperative ECMO

Table 5. Complications

Variable Major intraoperative complications n (%) Reoperation For bleeding n (%) Postoperative complications n (%) Renal failure requiring dialysis Postoperative ECMOd (severe PGD) Stroke/CVA Atrial fibrillation Mortality n (%) 30 days 6 months 1 year

p Value (CPB vs ECMO)

Off-Pump (n ¼ 374)

0.13

1 (0.3%)c 22 (5.9%)

(8.2%) (18.3%) (2.0%) (32.7%)

0.03 0.83 1.00 1.00

37 16 11 99

2 (4.1%) 7 (14.3%) 9 (19.1%)

1.00 1.00 –

9 (2.4%) 31 (8.3%) 52 (13.9%)

CPB (n ¼ 222)

ECMO (n ¼ 49)

1 (0.5%)a 39 (17%)

1 (2%)b 4 (8.2%)

49 34 7 69

(22.1%) (15.3%) (3.2%) (31.1%)

11 (5.0%) 32 (14.4%) 42 (18.9%)

4 9 1 16

p Value (3 Groups) < 0.01 < 0.01

(9.9%) (4.3%) (2.9%) (26.5%) < 0.01 < 0.01 < 0.01

a

b c d Aortic dissection. Air embolism. Cardiac arrest. ECMO within 7 days after lung transplant (excluding patients with ECMO Bridge who were left electively on ECMO and decannulated in < 24 hours).

CPB ¼ cardiopulmonary bypass; dysfunction.

CVA ¼ cerebrovascular accident;

ECMO ¼ extracorporeal membrane oxygenation;

PGD ¼ primary graft

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Table 6. Causes of Early and Late Mortality CPB 88 Deaths in 222 Patients Variable Number (%) Cause of mortality Graft failure Infection CVA Cardiovascular Malignancy Renal failure Other a

CPB vs ECMO, p ¼ 1.00.

ECMO 10 Deaths in 49 Patients

Early (< 30 Days)

Late (> 30 Days)

Earlya (< 30 Days)

Lateb (> 30 Days)

13 (5.6%)

75 (33.8%)

2 (4.1%)

8 (16.3%)

6 5

13 28 3 5 6 4 16

1 1

2 2

2 b

1 1 2

CPB vs ECMO, p ¼ 0.86.

CPB ¼ cardiopulmonary bypass;

CVA ¼ cerebrovascular accident;

included patients coming to the operating room on ECMO that had been used as a bridge to LT, we included these patients in the analysis. We recognize that there is a potential for selection bias due to the high proportion of these patients in the ECMO group (42.8% vs only 7.2% in the CPB group). Rapidly, we were able to confirm that VA ECMO provided adequate support during the LT procedure. As in the case of CPB, we were able to successfully complete LT procedures with peripheral cannulation in most of the cases where the anteroaxillary approach was utilized, and obtained adequate support using central cannulation in cases where the clamshell incision was utilized. In cases with profound lung involvement,

Fig 1. Kaplan-Meier survival curve. Cardiopulmonary bypass (CPB) versus extracorporeal membrane oxygenation (ECMO) versus off-pump lung transplant. (- - - - - - ¼ off-pump; — ¼ ECMO; – – – ¼ CPB.)

ECMO ¼ extracorporeal membrane oxygenation.

cardiomegaly, or inadequate hemodynamic stability on peripheral ECMO, central cannulation was considered. Because ECMO utilizes a closed circuit with elevated negative pressures, there is the potential for catastrophic air embolism. For this reason, soon after our initial experience we began using an integrated ECMO and CPB system. This system allows the recognition of significant air embolism (> 3 mm) and, because it includes a venous reservoir placed in parallel, an immediate initiation of full CPB can be applied, if necessary, without the need of a circuit change. In this initial experience, we were able to confirm the efficacy of ECMO as intraoperative support but also understand the limitations of this method. As previously observed by the Leipzig group [8], we found a significantly longer time of support with ECMO during the lung implantation. This is reflective of a system that is more sensitive to cardiac structure compression and volume load, which could profoundly affect ECMO flows and hemodynamic stability, delaying allograft implantation in some cases as compared with CPB, especially when performed with femoral cannulation and during LT through an anteroaxillary approach. Also, the longer time required to complete lung resection using lobar transplantation could also have contributed as this procedure was used more often in the ECMO group. We did not find a significant difference in perioperative transfusion of blood products but found a significantly higher rate of intraoperative RBC transfusion, in contradiction to other published series [12]. This could have been an effect of the high proportion of our patients in the ECMO group that had preoperative ECMO use with a significantly higher transfusion rate due to the long-term effects on ECMO on the coagulation system. Despite the high complexity of the ECMO group and higher rate of intraoperative RBC transfusion, these patients had fewer pulmonary and renal complications with less reintubation, tracheostomy, and need of dialysis compared with the CPB group. We also noted a trend toward decreased reoperation for bleeding in the ECMO

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group. The decreased activation of the inflammatory system and decreased hemolysis with contemporary ECMO systems [11] could be a valid explanation to support these differences in outcomes, although further studies are needed to support this theory.

Limitations Limitations of this study include the retrospective nature of this analysis and the difference in study periods where CPB and ECMO were predominantly used. We used CPB more often before 2012 and have used ECMO almost exclusively since 2012. There may also be an inherent selection bias as patients with preoperative ECMO as bridge to LT were included in this analysis. Patients who require ECMO as a bridge to LT comprise a high-risk population, were 42% of the ECMO group, and could have negatively influenced the outcomes of the ECMO patients, potentially masking a greater potential benefit of ECMO over CPB. Although we excluded 2 patients who underwent conversion from ECMO to CPB due to significant bleeding and inability to rapidly reinfuse the blood lost from our analysis, it is important to understand the potential need for emergent conversion in certain circumstances.

Conclusions The use of ECMO in LT is safe and in our experience was associated with a decreased rate of pulmonary and renal complications. These data support a contemporary paradigm shift toward ECMO as a method of intraoperative support. It is our current standard for LT. Further analysis is required to define the safety and efficacy of ECMO in a general transplant practice and long-term advantages of ECMO over CPB. We thank Shannon Wyszomierski, PhD, for editing the manuscript.

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References 1. Nagendran M, Maruthappu M, Sugand K. Should double lung transplant be performed with or without cardiopulmonary bypass? Interact Cardiovasc Thorac Surg 2011;12: 799–804. 2. Gammie JS, Cheul Lee J, et al. Cardiopulmonary bypass is associated with early allograft dysfunction but not death after double-lung transplantation. J Thorac Cardiovasc Surg 1998; 115:990–7. 3. Diamond JM, Lee JC, Kawut SM, et al. Clinical risk factors for primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med 2013;187:527–34. 4. Dalibon N, Geffroy A, Moutafis M, et al. Use of cardiopulmonary bypass for lung transplantation: a 10-year experience. J Cardiothorac Vasc Anesth 2006;20:668–72. 5. Bermudez CA, Adusumilli PS, McCurry KR, et al. Extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: long-term survival. Ann Thorac Surg 2009;87:854–60. 6. Toyoda Y, Bhama JK, Shigemura N, et al. Efficacy of extracorporeal membrane oxygenation as a bridge to lung transplantation. J Thorac Cardiovasc Surg 2013;145:1065–70. 7. Bermudez CA, Rocha RV, Zaldonis D, et al. Extracorporeal membrane oxygenation as a bridge to lung transplant: midterm outcomes. Ann Thorac Surg 2011;92:1226–31. 8. Bittner HB, Binner C, Lehmann S, Kuntze T, Rastan A, Mohr FW. Replacing cardiopulmonary bypass with extracorporeal membrane oxygenation in lung transplantation operations. Eur J Cardiothorac Surg 2007;31:462–7. 9. Shigemura N, Sclabassi RJ, Bhama JK, et al. Early major neurologic complications after lung transplantation: incidence, risk factors, and outcome. Transplantation 2013;95: 866–71. 10. Wan S, LeClerc JL, Vincent JL. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest 1997;112:676–92. 11. Fromes Y, Gaillard D, Ponzio O, et al. Reduction of the inflammatory response following coronary bypass grafting with total minimal extracorporeal circulation. Eur J Cardiothorac Surg 2002;22:527–33. 12. Ius F, Kuehn C, Tudorache I, et al. Lung transplantation on cardiopulmonary support: venoarterial extracorporeal membrane oxygenation outperformed cardiopulmonary bypass. J Thorac Cardiovasc Surg 2012;144:1510–6. 13. Aigner C, Wisser W, Taghavi S, et al. Institutional experience with extracorporeal membrane oxygenation in lung transplantation. Eur J Cardiothorac Surg 2007;31:468–74.

DISCUSSION DR BASAR SAREYYUPOGLU (Temple, TX): Some of these patients may just undergo to VV ECMO [venovenous extracorporeal membrane oxygenation] rather than VA [venoarterial] ECMO, especially hypoxemia driven hemodynamic problems that anesthesia cannot support single lung ventilation. And I believe you can get away, just doing so, for example, percutaneous cannulation to avoid hypoxemia in the operating room and you may not need VA ECMO further to protect the right ventricle. You may have an easier operation and have better outcomes by doing so. What do you think? I have not seen you mention about this approach in your cohort. DR BERMUDEZ: The reality is that we rarely do the transplant on VV ECMO. We have learned that most of the time it is difficult to maintain hemodynamic stability on VV ECMO alone. Patients on VV ECMO, due to the atrial compression when you are doing the procedure, become very unstable. We learned this with our

experience using ECMO in the patients that had ECMO as a bridge to transplant and decided to convert the vast majority of these patients to VA ECMO. Still occasionally, we find patients not able to tolerate VA ECMO who require CPB. As you see, the majority of the patients in this experience, with those patients that we had as a bridge to ECMO, we wanted to simplify the procedure. We took them to the OR [operating room], very sick as you understand, already on ECMO, we were not able to do it on VV-ECMO. So the reality is that we have utilized, mostly if not exclusively, the VA ECMO, a technique I did not review. There were very few cases that were attempted to be done on VV ECMO that were not reviewed in this experiment. DR SUDISH MURTHY (Cleveland, OH): Very nice presentation. You had a fairly long postoperative intubation period in both groups. It seems a little out of the norm for what we would expect

for a standard, single, or double lung transplant. These are clearly selected patients. They have probably higher LAS [lung allocation score] scores. Is that your explanation for that? DR BERMUDEZ: Thank you for your question. We were also surprised with the long ventilation required postoperatively, but we believe this is due to the high complexity of the cases, which is reflected in the LAS, especially in the ECMO group where close to 48% had ECMO used preoperatively as a bridge. DR WICKII VIGNESARAN (Chicago, IL): There were quite a large number of patients for a bridge in the ECMO group. Did you have any of those patients cannulated in the neck or

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subclavian, or are all of them through the groin cannulations? If cannulated in the neck how did you manage these patients? DR BERMUDEZ: That is a good question. We did not specify that on the presentation. A number of these patients that came to us on venovenous ECMO agreed to transplant, the ECMO group, were cannulated. We do all cannulation through the groin and neck. So what we did in those cases, we kept both cannulas, placed a third cannula in the femoral artery, used the two cannulas as venous drainage, reinfused through the femoral artery, and actually at the end of the procedure those were the six cases that were excluded. We removed them from VA-ECMO and initiated immediately venovenous ECMO, and kept the patients in the ICU [intensive care unit] and then cannulated in the ICU the next day, yes.

ABTS Requirements for the 10-Year Milestone for Maintenance of Certification Diplomates of the American Board of Thoracic Surgery (ABTS) who plan to participate in the 10-Year Milestone for the Maintenance of Certification (MOC) process as Certified-Active must hold an unrestricted medical license in the locale of their practice and privileges in a hospital accredited by the JCAHO (or other organization recognized by the ABTS). In addition, a valid ABTS certificate is an absolute requirement for entrance into the MOC process. If your certificate has expired, the only pathway for renewal of a certificate is to take and pass the Part I (written) and the Part II (oral) certifying examinations. The CME requirements are 150 Category I credits over a five-year period. At least half of these CME hours need to be in the broad area of thoracic surgery. Category II credits are not accepted. Interested individuals should refer to the Board’s website (www.abts.org) for a complete description of acceptable CME credits. Diplomates will be required to take and pass a secured exam after their application has been approved. Taking SESATS in lieu of the secured exam is not an option. The secured exam is administered over a two-week period in September of every year at Pearson Vue Testing Centers, which are located nationwide. Diplomates will have the opportunity to select the day and location of their exam. For the dates of the next MOC exam, visit the Board’s web site at www.abts.org.

Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier

The ABTS has voted to replace the requirement for mandatory database participation with Performance Improvement. The Board is considering the appropriate start date for the Performance Improvement process, but it will not be earlier than January 2016. For those who do not participate in a Board approved database/registry, the Board will continue to require participation in the Professional Portfolio until the Performance Improvement process starts. Diplomates may apply for MOC in the year their certificate expires or, if they wish to do so, they may apply up to two years before it expires. However, the new certificate will be dated 10 years from the date of expiration of their original certificate or most recent MOC certificate. In other words, going through the MOC process early does not alter the 10-year validation. Diplomates certified prior to 1976 (the year that time-limited certificates were initiated) are also required to participate in MOC if they wish to maintain valid certificates. Information outlining the rules, requirements, and application deadline for the 10-year Milestone of MOC in thoracic surgery is available on the Board’s website at www.abts.org. For additional information, please contact the American Board of Thoracic Surgery, 633 N Saint Clair St, Ste 2320, Chicago, IL 60611; telephone (312) 2025900; fax (312) 202-5960; e-mail: [email protected].

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