European Journal of Cardio-thoracic Surgery 39 (2011) e175—e180 www.elsevier.com/locate/ejcts

The use of non-heart-beating lung donors category III can increase the donor pool§

Caroline Van De Wauwer a,*, Erik A.M. Verschuuren b, Wim van der Bij b, George D. Nossent b, Michiel E. Erasmus a Downloaded from https://academic.oup.com/ejcts/article/39/6/e175/381303 by guest on 02 October 2021

a Department of Cardiothoracic Surgery, University Medical Centre Groningen, Groningen, The b Department of Pulmonary Disease and , University Medical Centre Groningen, Groningen, The Netherlands

Received 31 August 2010; received in revised form 23 December 2010; accepted 12 January 2011; Available online 3 March 2011

Abstract

Objective: The use of non-heart-beating (NHB) lung donors has been propagated as an alternative besides heart-beating (HB) lung donors to overcome organ shortage. We evaluated the effectiveness of NHB lung transplantation Methods: The donor and recipient data of all 35 NHB category III lung transplantations (LTx) between January 2005 and December 2009 were reviewed. For comparison, we collected recipient and donor data of a cohort of 77 HB lung transplantations. In both groups, we assessed survival, primary dysfunction (PGD), forced expiratory volume in 1 s (FEV1), acute rejection, and bronchiolitis obliterans syndrome (BOS). Results: Thirty-five NHB lung transplantations were performed, five single LTx and 30 bilateral LTx in 12 male and 23 female patients. The donor oxygenation capacity was 61 kPa (interquartile range (IQR), 56—64). Warm ischemia time in the donor was 29 min (IQR, 24—30). Cold ischemic time of the last implanted lung was 458 min (IQR, 392—522). Cardiopulmonary bypass was used 13 times. PGD (1—3) was observed in 45% of the patients at T0, in 42% at T24, in 53% at T48, and in 50% at T72. PGD 3 decreased from 24% at T0 to 6% at T72. The use of nitric oxide (NO) within 24 h after transplantation was necessary in three patients with successful weaning in all. There was no significant difference for donor and recipient characteristics between NHB and HB lung transplantations. Survival, occurrence of PGD, and acute rejection was equal to the HB cohort. The incidence of BOS was lower in the NHB group.

The measured FEV1 tended to be better in the NHB group. Conclusion: Lungs from nonheparinized category III NHB donors are well suited for transplantation and can safely increase the donor pool. # 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Keywords: Lung transplantation; Non-heart-beating donor; Primary graft dysfunction

1. Introduction NHB donor [5]. The Maastricht classification drawn up in 1995 classifies the NHB donors as uncontrolled or controlled The first lung transplantation was performed by James donors [6]. In category I (dead on arrival) and category II Hardy in 1963 with a graft from a non-heart-beating (NHB) (failed resuscitation), cardiac death occurs unexpectedly donor [1]. Since the criteria for brain death were and the situation for organ recovery is therefore ‘uncon- introduced and accepted in 1968, transplantation with trolled’. In category III (withdrawal of life support, awaiting lungs from heart-beating (HB) donors became the mainstay cardiac arrest) and category IV (cardiac arrest in brain-dead therapy for patient with end-stage lung disease refractory donor), circulatory arrest is anticipated and organs can be to medical therapy. Until today, donor organ shortage is the recovered under ‘controlled’ circumstances. Steen et al. main limiting factor for this treatment. It is estimated that performed the first transplant from an uncontrolled donor only 15—30% of all HB donors have lungs that are suitable for in 2000 after ex vivo evaluation of the lungs [7]. transplantation [2,3]. This resulted in the reintroduction of Subsequently de Antonio et al. reported lung transplanta- the concept of lung transplantation from NHB donors by tion using Maastricht category I and II donors [8].The Egan in 1991 [4]. In 1995, Love et al. performed the first experience with the use of controlled donors, mainly clinical successful lung transplantation with lungs from an Maastricht category III, is growing. This has been reported in recent articles [9—18]. § Presented at the 24th Annual Meeting of the European Association for The purpose of this study is to investigate whether the use Cardio-Thoracic Surgery, Geneva, Switzerland, 11—15 September 2010. of lungs from controlled NHB donors category III is a true * Corresponding author. Address: Department of Cardiothoracic Surgery, alternative besides HB lung donors by comparing primary University Medical Centre Groningen, Hanzeplein 1 PO Box 30001, 9700 RB Groningen, The Netherlands. Tel.: +31 50 3616161. graft dysfunction, development of bronchiolitis obliterans E-mail address: [email protected] (C. Van De Wauwer). syndrome (BOS), lung function, and survival.

1010-7940/$ — see front matter # 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejcts.2011.01.035 e176 C. Van De Wauwer et al. / European Journal of Cardio-thoracic Surgery 39 (2011) e175—e180

2. Patients and methods compared in all lung transplantations and separately in bilateral lung transplantations [19]. 2.1. Study group 2.5. Acute rejection and BOS Between January 2005 and December 2009, a total of 145 lung transplantations were performed in our center. Among Bronchoscopy was performed at discharge from the these patients, 35 adults received lungs from category III NHB hospital and thereafter when clinically indicated. Acute donors. For this retrospective study, the data of the 35 adult rejection was based on histological findings and was graded NHB recipients were assessed and compared with an existing according to the recommendations of the ISHLT Lung cohort of 77 adult HB recipients that were transplanted Rejection Study Group [20]. during the same time period. All recipients received induction therapy with basiliximab and triple maintenance immunosuppression with corticos- 2.2. Donor protocol teroids, tacrolimus, and azathioprine or mycophenalate. BOS was defined as a decrease in forced expiratory volume Downloaded from https://academic.oup.com/ejcts/article/39/6/e175/381303 by guest on 02 October 2021 Heart-beating donors (HBD) and non-heart-beating donors in 1 s (FEV1) compared to the baseline value and was (NHBD) were selected according to the standard International classified following the recommendations of the ISHLT in BOS Society for Heart and Lung Transplantation (ISHLT) criteria. grade 0—3 [21]. When donation is considered, the Dutch National Donor Registry is checked to see whether the patient is registered 2.6. Lung function positive as a donor. Blood group, gender, length, age, medical history, blood gas measurement, and a recent chest X-ray are Lung function assessment was performed at every hospital necessary for a first assessment. If judged suitable, a blood gas visit. For this study, we report the FEV1 at 3 months, 6 at 100% oxygen after at least 10 min of ventilation with months, 1 year, and 2 years after transplantation. The FEV1 is expressed as a percentage of the predicted FEV1 of the 5cmH2O positive end-expiratory pressure (PEEP) and a bronchoscopy are performed for final assessment of the recipient. suitability of the lungs for transplantation. After acceptance of an NHB donor, a time of withdrawal is agreed so that all the 2.7. Variables transplant teams can be present in the donor hospital in time. The technical procedure of withdrawal is up to the treating Data of 112 patients (35 NHB and 77 HB) were reviewed for physicians and local protocols. No heparin is given before donor variables and recipient variables. Age, gender, PaO2 withdrawal of treatment. After circulatory arrest, a 5-min no- after minimal 10 min of 100% oxygen and a PEEP of 5 cmH2O, touch period was respected. If necessary, the patient was days of mechanical ventilation, time until circulatory arrest, reintubated and a bronchoscopy was performed. Lungs are cause of brain damage, warm ischemic time, and ischemic preserved in our standard way with in situ anterograde flush time of the last implanted lung were recorded as donor and and a retrograde flush on the back table both with Perfadex. preservation variables. Recipient variables collected were The lungs are gently inflated and stored in Perfadex cooled by age, gender, LTx type, use of cardiopulmonary bypass, surrounding ice. The acceptable time between withdrawal of diagnosis, hospital stay, intensive care unit (ICU) stay, and treatment and occurrence of circulatory arrest was 1 h. The days of postoperative ventilation. accepted warm ischemia time was 1 h and was defined as the time between circulatory arrest and start of the anterograde 2.8. Statistical analysis flush. Cold ischemic time was defined as the interval between start of the anterograde flush in the donor and the reperfusion Data analysis was performed using Graphpad Prism 5 (San of the last implanted lung [14]. Diego, CA, USA). All data are expressed as median (interquartile ranges) unless otherwise defined. Mann— Whitney test, the Fisher’s exact test, and the chi-square 2.3. Recipient selection test were used to test for significances between both groups. For PGD and BOS, a chi-square test was used to test for a Recipient selection and donor/recipient matching were significant difference between both groups at each time performed using international guidelines. All recipients on point. The Kaplan—Meier method was used to assess the the waiting list were candidates for both HB lungs and NHB patient survival. A p-value <0.05 was considered significant. lungs. Lung allocation was based on the waiting time on the waiting list or urgency status according to Eurotransplant allocation rules. 3. Results

2.4. Primary graft dysfunction 3.1. Donors and preservation

Primary graft dysfunction (PGD) was graded according to Between January 2005 and December 2009, a total of 61 the recommendations of the ISHLTconsidering the PaO2/FiO2 lungs from NHB category III donors were offered to our ratio and the findings on chest X-ray. The incidence was institution. In six cases the lungs were considered but not compared at different time points (T0 — within 6 h of accepted because of medical reasons. Logistic reasons, reperfusion, T24, T48, and T72). PGD was assessed and including no transplant capacity (n = 4), no suitable recipient C. Van De Wauwer et al. / European Journal of Cardio-thoracic[()TD$FIG] Surgery 39 (2011) e175—e180 e177

Table 1. Donor and preservation characteristics.

NHB (n = 35) HB (n = 77) p value

Age (years) 47 (35—55) 46 (31—53) NS Female (%) 68.6 51.9 NS pO2 at 100% (kPa) 61 (56—64) 61 (53—67) NS Time on ventilator (days) 2 (1—6) 1.5 (1—2.5) NS Brain damage (%) ICB 37.1 29.9 SAB 25.7 36.4 Brain anoxia 20 1.3 Head trauma 11.4 26 Miscellaneous 5.7 6.4 Circulatory arrest (min) 17 (10—39) Warm ischemia (min) 29 (24—30) Cold ischemia (min) 458 (392—522) 401 (357—488) NS Downloaded from https://academic.oup.com/ejcts/article/39/6/e175/381303 by guest on 02 October 2021

ICB, intracranial bleeding; SAB, subarachnoidal bleeding; NHB, non-heart- beating; HB, heart-beating. Data are expressed as median (interquartile ranges) unless otherwise defined.

(n = 2), and miscellaneous (n = 2) were other reasons to reject the lungs. Forty-seven NHB donor procedures were started resulting in 35 adult NHB lung donations and transplantations and one pediatric lung transplantation. Reasons for not using lungs after the donor procedure was started were absence of cardiac arrest within 1 h (n = 7), emphysematous lung at inspection (n = 2), infection (n = 1), and lung edema after flush (n = 1). Fig. 1. (A) Primary graft dysfunction (PGD) after lung transplantation in non- heart-beating donors (NHB) and heart-beating donors (HB) at T0, T24, T48 and Donor characteristics are listed in Table 1. In the NHB T72. (B) PGD in NHB and HB after bilateral lung transplantation at different group, circulatory arrest occurred within 17 min (interquar- time points. Percentage of the recipient in each PGD grade at different time tile range (IQR), 10—39 min). The median warm ischemic points. time was 29 min (IQR, 24—30 min). The cold ischemic time for the last implanted lung was 458 min (IQR, 392—522) in NHB Time to extubation, stay in the ICU, and hospital stay were compared to 401 (IQR, 357— 88) in HB ( p = 0.18). There was comparable in both groups. no statistical significant difference between NHB an HB. 3.3. Primary graft dysfunction 3.2. Recipient characteristics PGD (grade 1—3) in the NHB group was observed in 45% of Recipient characteristics are shown in Table 2. Thirty-five the patients at T0, in 42% at T24, in 53% at T48, and in 50% at NHB lung transplantations were performed, five single LTx T72. PGD grade 3 decreased from 24% at T0 to 6% at T72. and 30 bilateral LTx in 12 male and 23 female patients. Three There was no significant difference in PGD between both the patients underwent a retransplantation for progressive BOS. groups at different time points, although the decrease in PGD 3 was less in the HB group compared to that in the NHB group (from 25% to 11% vs from 24% to 6%) (Fig. 1A). When assessing Table 2. Recipient characteristics.

NHB (n = 35) HB (n = 77) p value [()TD$FIG]

Age (years) 54 (41—60) 53 (40—59) NS Female (%) 65.7 49.4 NS BLTx (%) 85.7 71.4 NS CPB used (%) 40 39 NS High urgent (%) 40 45 NS Lung disease (%) Emphysema 45.7 46.7 Cystic fibrosis 14.3 15.6 Lung fibrosis 20.0 23.4 PH 3.0 2.6 BO 17 3.9 Other — 7.8 Hospital stay (days) 32 (24—66) 33 (26—46) NS ICU Stay (days) 4 (3—24) 5 (2—14) NS Ventilation postop (days) 2 (1—3) 2 (1—8) NS

BLTx, bilateral lung transplantation; CPB, cardiopulmonary bypass; PH, pul- Fig. 2. The incidence of bronchiolitis obliterans syndrome (BOS) in the non- monary hypertension; BO, bronchiolitis obliterans; NHB, non-heart-beating; heart-beating donor (NHB) and the heart-beating donor (HB) at 6 months, 1 HB, heart-beating. Data are expressed as median (interquartile ranges) unless year and 2 years after transplantation. Percentage of the recipient in each BOS otherwise defined. grade at different time points. e178 C. Van De Wauwer et al. / European Journal of Cardio-thoracic Surgery 39 (2011) e175—e180

Table 3. Transplant function as percentage of predicted forced expiratory the predicted FEV1 tended to be better in the NHB group volume in 1 s (FEV1). compared to that in the HB group at 3 months, 6 months, 1 3 months 6 months 1 year 2 years year, and 2 years (Table 3).

NHB n 32 32 26 15 3.6. Survival

% FEV1 75 (54—90) 82 (57—97) 87 (63—101) 85 (62—112) HB Recipient survival is shown in Fig. 3. There was no n 68 67 67 60 significant difference between the NHB group and the HB % FEV1 69 (54—85) 74 (58—92) 78 (56—96) 79 (57—97) p value 0.40 0.50 0.19 0.31 group ( p = 0.53). Five patients in the NHB group died during follow-up. Graft failure caused by BOS was the reason in of NHB, non-heart-beating; HB, heart-beating. Data are expressed as median death in two patients. In the HB group, 22 patients died (interquartile ranges). during follow-up. Two patients died of PGD shortly after transplantation and two patients died due to graft failure. and comparing only the bilateral lung transplantations, NHB Downloaded from https://academic.oup.com/ejcts/article/39/6/e175/381303 by guest on 02 October 2021 lungs had less PGD at T0 and T24 (Fig. 1B). The use of inhaled NO within 24 h after lung transplanta- 4. Discussion tion was necessary in three patients in the NHB group. There were no patients that required postoperative extracorporeal To our knowledge, this is the largest single-center study membrane oxygenation (ECMO) support. The use of NO was reporting the use of lungs from NHBDs category III. The necessary in three patients in the HB group. One was presented study shows that lungs from category III NHB successfully weaned, one died of PGD, and one was donors perform well compared to lungs from HBDs. successfully weaned after ECMO. Importantly there was no difference in survival at 1 year. Furthermore, postoperative ventilation, discharge from ICU, 3.4. Acute rejection and BOS and discharge from the hospital were comparable in both the groups. Finally, in the NHB group there seemed to be less PGD In the NHB group, two patients (5.7%) developed acute 3 (3—24%), the FEV1 was higher during follow-up and the rejection (A2) at 1 month and at 23 months after incidence of BOS was lower compared to the HB group, transplantation. A1 rejection was detected in two patients although this was not significant. (2.6%) at 3 months and at 6 months in the HB group. The NHBD program started in 2004 after the initiation of a The incidence of BOS was lower in the NHB group compared renewed national protocol for NHB multiorgan donation by to that in the HB group (Fig. 2). At 1 year after transplantation, the Dutch Transplant Foundation (NTS). Since then, the there was no BOS in the NHB group compared to that in the HB number of NHBD has increased from four in 2005 up to 12 in group (100% BOS 0 vs 85% BOS 0, p = 0.037). 2009. In 2008 and 2009, 40% and 37.5% respectively of our transplants were performed with NHBDs. 3.5. Lung function Our results with category III NHB donor lungs are comparable with the results of other NHB programs [9,15— Although there was no significant difference, lung 17]. In contrast, the Madrid group [8] with an uncontrolled function after transplantation assessed as a percentage of NHB donor program reported a PGD 3 in 29% of their patients. [()TD$FIG] This higher percentage PGD might be explained by the longer warm ischemic time (118 min) and the acute and less- controlled nature of the uncontrolled NHB donor procedure. Finally, their lung function evaluation is less precise since there are no standard lung function data available in category I and category II NHBDs. Although their reported 1-year and 3-year survival after NHB donation is lower than in our study, this lower survival was not different to their HB results. The recent annual report of the ISHLT shows that acute rejection is detected in 36% of the patients in the first year after lung transplantation [22]. In our study, 2.8% in the NHB group developed A2 rejection and A1 rejection was detected in 2.6% of the patients in the HB group. This might be explained by tacrolimus-based immunosuppression regimen and by the use of induction therapy with an IL-2R antagonist. However, we only report the histological confirmed acute rejection. Our lower incidence is confirmed by the experi- ence of other transplant groups [10,12,13,16,17]. BOS is present in more than 20% of the patients 2 years after transplantation and is one of the most common causes Fig. 3. Patient survival. NHB, non-heart-beating donor; HB, heart-beating of death 1 year after transplantation [22]. Our study donor. demonstrates 0% of BOS in the NHB group and 15% of BOS C. Van De Wauwer et al. / European Journal of Cardio-thoracic Surgery 39 (2011) e175—e180 e179 in the HB group 1 year after transplantation. After 2 years, agonal phase, and for assessment of lungs from uncontrolled the incidence between both groups is comparable. We NHBDs, leading to the expansion of the NHB donor pool. hypothesize that the decrease of inflammatory lung injury The present study suffers from some limitations. First, the before retrieval in the NHBD as shown in animal experiments study was retrospective and the experience increased with may be responsible for the lower BOS incidence at 6 months the amount of retrievals and transplantations performed. and 1 year after transplantation. Second, the patients were not randomly assigned to a specific There are differences between category III NHB donation type of donor. Third, there were more patients with programs. Pretreatment (i.e., heparin or phentolamine) was bronchiolitis obliterans in the NHB group compared to that given before death [10,12,13] or after the 5-min interval [17] in the HB group. Therefore, the findings need to be confirmed in other protocols. We only optimized the donor treatment with a prospective study. before switch-off but added no treatment [14]. In conclusion, this study demonstrates comparable out- It is difficult to compare our warm ischemia with others. In come between NHBDs and HBDs, thereby confirming that our protocol warm ischemic time (WIT) was defined as the lungs from NHBDs may be a safe alternative to increase the time between circulatory arrest and start of the anterograde donor pool. Downloaded from https://academic.oup.com/ejcts/article/39/6/e175/381303 by guest on 02 October 2021 flush which is comparable with the report of De Vleeschauwer et al. [13]. But it is different from the data reported by Snell et al. where WIT was defined as the time between the References absence of cardiac output and the start of cold flush preservation [18]. In other reports WIT is defined as part of [1] Hardy JD, Webb WR, Dalton Jr ML, Walker Jr GR. Lung homotransplanta- the interval or the interval between withdrawal of life tion in man. JAMA 1963;186:1065—74. support and establishing perfusion of the donor lung with cold [2] Egan TM, Boychuk JE, Rosato K, Cooper JD. Whence the lungs? A study to preservation solution [10,12] and in some studies WIT is not assess suitability of donor lungs for transplantation. Transplantation reported [15,17]. 1992;53:420—2. [3] Van Raemdonck DE, Rega FR, Neyrinck AP, Jannis N, Verleden GM, Lerut The most common factor in all reported series is the use of TE. Non-heart-beating donors. Semin Thorac Cardiovasc Surg 2004;16: an anterograde flush followed by a retrograde flush through 309—21. each of the pulmonary veins to remove any pulmonary [4] Egan TM, Lambert Jr CJ, Reddick R, Ulicny Jr KS, Keagy BA, Wilcox BR. A microthrombi. strategy to increase the donor pool: use of cadaver lungs for transplan- tation. Ann Thorac Surg 1991;52:1113—20. We believe that the applied retrograde flush is essential [5] Love RB, Stringham JC, Chomiak PN. Successful lung transplantation using for our good results in the Dutch situation where no heparin is a non-heart-beating donor. J Heart Lung Transplant 1995;14:S88. used before withdrawal of treatment. [6] Kootstra G, Daemen JH, Oomen AP. Categories of non-heart-beating Although the number of NHBDs used is growing, there is donors. Transplant Proc 1995;27:2893—4. still a potential pool of controlled NHBDs (category III) [23] [7] Steen S, Sjoberg T, Pierre L, Liao Q, Eriksson L, Algotsson L. Transplanta- tion of lungs from a non-heart-beating donor. Lancet 2001;357:825—9. and uncontrolled NHBDs (categories I and II) that is not used. [8] de Antonio DG, Marcos R, Laporta R, Mora G, Garcia-Gallo C, Gamez P, Evaluation of lungs in the uncontrolled donor remains Cordoba M, Moradiellos J, Ussetti P, Carreno MC, Nunez JR, Calatayud J, challenging in the absence of arterial blood gases and del RF,Varela A. Results of clinical lung transplant from uncontrolled non- previous medical history. The Madrid group initially eval- heart-beating donors. J Heart Lung Transplant 2007;26:529—34. [9] Butt TA, Aitchison JD, Corris PA, Wardle J, Clark S, Dark JH. Lung uated the lungs using a pulmonary artery flush technique. At transplantation from deceased donors without pre-treatment. J Heart the time of , 300 ml of donor blood was Lung Transplant 2007;26:S110. taken. After an initial flush with Perfadex, the blood was [10] Cypel M, Sato M, Yildirim E, Karolak W, Chen F,Yeung J, Boasquevisque C, flushed through the pulmonary artery. Subsequently, arterial Leist V, Singer LG, Yasufuku K, Deperrot M, Waddell TK, Keshavjee S, blood gas analysis, corrected for temperature, was per- Pierre A. Initial experience with lung donation after cardiocirculatory death in Canada. J Heart Lung Transplant 2009;28:753—8. formed on the effluent from the left atrium. [11] Dark JH. Lung transplantation from the non-heart beating donor. Trans- Recently, lungs were assessed using an ex vivo lung plantation 2008;86:200—1. perfusion (EVLP) system before implantation [24]. After [12] De Oliveira NC, Osaki S, Maloney JD, Meyer KC, Kohmoto T, D’Alessandro assessing three lung blocks, two with a DPO > 400 mmHg AM, Love RB. Lung transplantation with donation after cardiac death 2 donors: long-term follow-up in a single center. J Thorac Cardiovasc Surg were deemed acceptable for transplantation. 2010;139:1306—15. The first successful lung transplantation after ex vivo lung [13] De Vleeschauwer S, Van Raemdonck D, Vanaudenaerde B, Vos R, Meers C, perfusion was performed by Steen et al. in 2001 [7]. After Wauters S, Coosemans W, Decaluwe H, De LP,Nafteux P,Dupont L, Lerut T, 65 min of warm ischemia, 3 h of topical, an ex vivo functional Verleden G. Early outcome after lung transplantation from non-heart- beating donors is comparable to heart-beating donors. J Heart Lung assessment at 37 8C and further 8 h of cold storage successful Transplant 2009;28:380—7. right lung transplantation was performed. Since then, EVLP is [14] Erasmus ME, Verschuuren EA, Nijkamp DM, Vermeyden JW, van der BW. investigated extensively not only as a method to assess donor Lung transplantation from nonheparinized category III non-heart-beating lungs but also as a tool to preserve and resuscitate donor donors. A single-centre report. Transplantation 2010;89:452—7. lungs for a longer period of time [3,25]. Currently, all the [15] Mason DP,Thuita L, Alster JM, Murthy SC, Budev MM, Mehta AC, Pettersson GB, Blackstone EH. Should lung transplantation be performed using lungs with a donor arrest time longer than 30 min are donation after cardiac death? The United States experience. J Thorac assessed with EVLP in Toronto [10]. Other groups also have Cardiovasc Surg 2008;136:1061—6. successfully transplanted lungs from controlled NHBDs after [16] McKellar SH, Durham III LA, Scott JP,Cassivi SD. Successful lung transplant EVLP. The use of EVLP looks at the perspective for re- from donor after cardiac death: a potential solution to shortage of thoracic organs. Mayo Clin Proc 2010;85:150—2. assessment of rejected NHB donor lungs, for assessment of [17] Puri V,Scavuzzo M, Guthrie T,Hachem R, Krupnick AS, Kreisel D, Patterson NHB donor lungs after a prolonged period of warm ischemia or GA, Meyers BF. Lung transplantation and donation after cardiac death: a after a period of cardiopulmonary instability during the single center experience. Ann Thorac Surg 2009;88:1609—14. e180 C. Van De Wauwer et al. / European Journal of Cardio-thoracic Surgery 39 (2011) e175—e180

[18] Snell GI, Levvey BJ, Oto T, McEgan R, Pilcher D, Davies A, Marasco S, at the lungs to see how the lungs are performing during ventilation at that Rosenfeldt F. Early lung transplantation success utilizing controlled do- moment. nation after cardiac death donors. Am J Transplant 2008;8:1282—9. For your question about evaluation of the lungs, we use the standard

[19] Lee JC, Christie JD, Keshavjee S. Primary graft dysfunction: definition, criteria that we use for our heart-beating lung donors. We accept a PaO2/FiO2 risk factors, short- and long-term outcomes. Semin Respir Crit Care Med ratio above 40 kPa and almost no infiltrates on chest X-ray, but we also have 2010;31:161—71. some donors that are going more in the direction of marginal donors with good [20] Yousem SA, Berry GJ, Cagle PT, Chamberlain D, Husain AN, Hruban RH, results. At least in one case, we have used lungs from a non-heart-beating Marchevsky A, Ohori NP, Ritter J, Stewart S, Tazelaar HD. Revision of the donor with an age over 60. I know of one case where the left lung was not 1990 working formulation for the classification of pulmonary allograft accepted because of infection. We had a look at the lungs. In one segment of rejection: Lung Rejection Study Group. J Heart Lung Transplant 1996; the right lower lobe there was also an infection. At bronchoscopy there was a 15:1—15. mucus plug sitting in that particular segment which was aspirated. We took it [21] Estenne M, Maurer JR, Boehler A, Egan JJ, Frost A, Hertz M, Mallory GB, with us for culture and we decided to use the lung and treat the patient with Snell GI, Yousem S. Bronchiolitis obliterans syndrome 2001: an update of antibiotics afterwards. In this case we also had a good result. the diagnostic criteria. J Heart Lung Transplant 2002;21:297—310. Dr Clark: And what time are you accepting before cardiac arrest? We’re [22] Christie JD, Edwards LB, Aurora P,Dobbels F,Kirk R, Rahmel AO, Stehlik J, accepting about 60 minutes. Taylor DO, Kucheryavaya AY, Hertz MI. The registry of the international Dr Van De Wauwer: We are using about 60 minutes at this moment, unless Downloaded from https://academic.oup.com/ejcts/article/39/6/e175/381303 by guest on 02 October 2021 society for heart and lung transplantation: twenty-sixth official adult lung we see that the patient is very stable and there are no fluctuations in heart and heart—lung transplantation report — 2009. J Heart Lung Transplant rate, no fluctuations in blood pressure, then sometimes we wait longer. Also, 2009;28:1031—49. when we have the information at 60 minutes that they don’t think it’s going to [23] Nijkamp DM, van der BW, Verschuuren EA, Heemskerk MB, de BE, Erasmus take long because the blood pressure is dropping and also the heart rate is ME. Non-heart-beating lung donation: how big is the pool? J Heart Lung dropping, then also we will be willing to wait longer to see what’s happening. Transplant 2008;27:1040—2. Dr M. Cypel (Toronto, Canada): This will be the largest single-center [24] Moradiellos Diez FJ, Naranjo JM, Cordoba M, Salas C, Alvarez J, Valle M, experience published to-date if you publish this now. Gomez de Antonio D, Campo-Canaveral JL, Crowley S, Varela de Ugarte A. We started our series more recently and we have done 26 cases so far, and First successful transplantations after ex vivo evaluation of uncontrolled we had exactly the same experience, with a low incidence of PGD. In terms of non-heart-beating donor human lungs. Interact Cardiovasc Thorac Surg the acceptance time, how long do you wait? I understand that you already 2010;11:S18—9. partially answered that, but we have accepted even up to 2 hours, and if the [25] Van Raemdonck D. Thoracic organs: current preservation technology and arrest happens between 1 and 2 hours, we do ex vivo lung perfusion in all of future prospects; part 1: lung. Curr Opin Organ Transplant 2010;15:150—5. those cases, and we have done 6 cases in which the scenario was exactly that. It is really helpful in that unpredictable situation. Appendix A. Conference discussion Dr Van De Wauwer: I think that’s a good comment, and we’re probably going to also go in that direction in the near future. Dr S. Clark (Newcastle Upon Tyne, United Kingdom): In common with your Dr Clark: I would also agree with that strategy. I think it makes a lot of experience, we are finding that around 10% to 15% of our transplant activity is sense and something that we’re moving towards as well. now from non-heart-beating organ donors. Could you elaborate a little bit on Dr L. Hamilton (Newcastle Upon Tyne, United Kingdom): It raises lots of the method that you use for retrieval; in particular, the stand-off time? Also, ethical questions as well. One question regarding interventions in the donor give us some more detail about how you evaluate the donor and which patients before death has occurred — you said you don’t give heparin beforehand, and I you would accept and those that you would reject. understand the reasons for that. What do you think of the concept of giving Dr Van De Wauwer: For the first question about the stand-off time, there is heparin to improve the quality of the organs? a no-touch period of 5 minutes. This is after the start of the circulatory arrest. Dr Van De Wauwer: Yes, indeed it is an ethical discussion and it differs But we agree that during the time, the patient can be transported to the from country to country, but in the Netherlands we agreed not to give any operating theater. It’s decided with the family of the patient before we heparin, and we didn’t see any problems without the heparin. We had one withdraw treatment if there is going to be an extubation, yes or no. If the patient where we saw at the retrograde flush that there were some clots patient is extubated, after the 5 minutes of no touch and when the patient coming out of the pulmonary artery, but even that patient had no problems arrives in the operating theater, the anesthetist again performs an intubation. after the operation. We had 2 patients where we needed to give nitric oxide. We always have a chest physician with us who performs a bronchoscopy at that After the operation, they were weaned successfully off the NO, but when we time. At the moment that the abdominal team is doing the laparotomy, we do looked back at the data, this had nothing to do with problems with the flush the sternotomy. We ask them if they need a hand to put the clamp on the aorta. and there were no reasons for pulmonary emboli at that moment or during the If that’s the case, we first put the clamp on the aorta, and then we have a look operation.