Criteria Donor Lungs Research Articles

Normothermic ex-vivo preservation with the portable Organ Care System Lung device for bilateral lung transplantation (INSPIRE): a randomised, open-label, non-inferiority, phase 3 study

Severe primary graft dysfunction (PGD) of grade 3 (PGD3) is a common serious complication following lung transplantation. We aimed to assess physiological donor lung preservation using the Organ Care System (OCS) Lung device compared with cold static storage. In this non-inferiority, randomised, controlled, open-label, phase 3 trial (INSPIRE) recipients were aged 18 years or older and were registered as standard criteria primary double lung transplant candidates. Eligible donors were younger than 65 years old with a ratio of partial pressure of oxygen in arterial blood to the fraction of inspired oxygen of more than 300 mm Hg. Transplant recipients were randomly assigned (1:1) with permuted blocks, stratified by centre, to receive standard criteria donor lungs preserved in the OCS Lung device (OCS arm) or cold storage at 4°C (control arm). The composite primary effectiveness endpoint was absence of PGD3 within the first 72 h after transplant and 30-day survival in the per-protocol population, with a stringent 4% non-inferiority margin. Superiority was tested upon meeting non-inferiority. The primary safety endpoint was the mean number of lung graft-related serious adverse events within 30 days of transplant. We did analyses in the per-protocol and intention-to-treat populations. This trial is registered with ClinicalTrials.gov, number NCT01630434. Between Nov 17, 2011, and Nov 24, 2014, we randomly assigned 370 patients, and 320 (86%) underwent transplantation (n=151 OCS and n=169 control); follow-up was completed in Nov 24, 2016. The primary endpoint was met in 112 (79·4%) of 141 patients (95% CI 71·8 to 85·8) in the OCS group compared with 116 (70·3%) of 165 patients (62·7 to 77·2) in the control group (non-inferiority point estimate -9·1%; 95% CI -∞ to -1·0; p=0·0038; and superiority test p=0·068). Patient survival at day 30 post-transplant was 135 (95·7%) of 141 patients (95% CI 91·0-98·4) in the OCS group and 165 patients (100%; 97·8-100·0) in the control group (p=0·0090) and at 12 months was 126 (89·4%) of 141 patients (83·1-93·9) for the OCS group compared with 146 (88·1%) of 165 patients (81·8-92·8) for the control group. Incidence of PGD3 within 72 h was reported in 25 (17·7%) of 141 patients in the OCS group (95% CI 11·8 to 25·1) and 49 (29·7%) of 165 patients in the control group (22·8 to 37·3; superiority test p=0·015). The primary safety endpoint was met (0·23 lung graft-related serious adverse events in the OCS group compared with 0·28 events in the control group [point estimate -0·045%; 95% CI -∞ to 0·047; non-inferiority test p=0·020]). In the intention-to-treat population, causes of death at 30 days and in hospital were lung graft failure or lung infection (n=2 for OCS vs n=7 for control), cardiac causes (n=4 vs n=1), vascular or stroke (n=3 vs n=0), metabolic coma (n=0 vs n=2), and generalised sepsis (n=0 vs n=1). The INSPIRE trial met its primary effectiveness and safety endpoints. Although no short-term survival benefit was reported, further research is needed to see whether the reduced incidence of PGD3 within 72 h of a transplant might translate into earlier recovery and improved long-term outcomes after lung transplantation. TransMedics Inc.

Long Term Outcomes of Ex Vivo Lung Perfusion: A Single Center 10 Year Experience

Waiting list mortality for lung transplantation is 15-25%, while only 20% of lungs from multiorgan donors are deemed suitable for transplantation. Ex vivo lung perfusion (EVLP) is a technique to increase the donor pool by reassessing and reconditioning extended criteria donor lungs (ED) that would otherwise be rejected. Previous studies have shown non-inferior short- and mid-term outcomes in EVLP lung transplantation using these lungs. Here, we report the long-term follow-up of our EVLP recipients.

Lung transplantation in the elderly: Influence of age, comorbidities, underlying disease, and extended criteria donor lungs

ObjectiveAs large registries show an increased risk for lung transplant recipients aged 60 years or more, few single centers report favorable outcomes for carefully selected older recipients without providing essential details. The purpose of our study was to determine variables that influence survival in the elderly. MethodsAll adult bilateral first lung transplants between January 2000 and December 2014 were divided in 2 groups: those aged less than 60 years (N = 223) and those aged 60 years or more (N = 83). The Charlson-Deyo Index determined recipient comorbidities. The Oto Donor Score assessed donor lung quality. ResultsRecipients aged 60 years or more had a significant lower median survival compared with their younger counterparts (48 vs 112 months, respectively, P < .001). Recipient age was as an exponentially increasing univariate risk factor for mortality. By adjusting for variables in multivariate analysis, this trend was nonsignificant. The displacing variables were idiopathic pulmonary fibrosis (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.0-2.2), Charlson-Deyo Index 2 or greater (HR, 1.3; 95% CI, 1.0-1.8), systemic hypertension (HR, 1.7; 95% CI, 1.2-2.6), gastroesophageal reflux (HR, 1.9; 95% CI, 1.1-3.1), diverticulosis (HR, 1.7; 95% CI, 1.0-2.7), and an Oto Donor Score 8 or greater (HR, 1.5; 95% CI, 1.1-2.0). All of these risk factors were significantly more likely to occur in recipients aged 60 years or more, except for a tendency for high Charlson-Deyo Index. ConclusionsThe comorbidity profile, underlying disease, and donor lung quality appear to be more important than age in reducing long-term survival. Older age serves as a marker for a complex constellation of factors that might be considered the relative or absolute contraindication to lung transplantation rather than age, per se.

The role of interleukin-1β as a predictive biomarker and potential therapeutic target during clinical ex vivo lung perfusion

BackgroundExtended criteria donor lungs deemed unsuitable for immediate transplantation can be reconditioned using ex vivo lung perfusion (EVLP). Objective identification of which donor lungs can be successfully reconditioned and will function well post-operatively has not been established. This study assessed the predictive value of markers of inflammation and tissue injury in donor lungs undergoing EVLP as part of the DEVELOP-UK study.MethodsLongitudinal samples of perfusate, bronchoalveolar lavage, and tissue from 42 human donor lungs undergoing clinical EVLP assessments were analyzed for markers of inflammation and tissue injury. Levels were compared according to EVLP success and post-transplant outcomes. Neutrophil adhesion to human pulmonary microvascular endothelial cells (HPMECs) conditioned with perfusates from EVLP assessments was investigated on a microfluidic platform.ResultsThe most effective markers to differentiate between in-hospital survival and non-survival post-transplant were perfusate interleukin (IL)-1β (area under the curve = 1.00, p = 0.002) and tumor necrosis factor-α (area under the curve = 0.95, p = 0.006) after 30 minutes of EVLP. IL-1β levels in perfusate correlated with upregulation of intracellular adhesion molecule-1 in donor lung vasculature (R2 = 0.68, p < 0.001) and to a lesser degree upregulation of intracellular adhesion molecule-1 (R2 = 0.30, p = 0.001) and E-selectin (R2 = 0.29, p = 0.001) in conditioned HPMECs and neutrophil adhesion to conditioned HPMECs (R2 = 0.33, p < 0.001). Neutralization of IL-1β in perfusate effectively inhibited neutrophil adhesion to conditioned HPMECs (91% reduction, p = 0.002).ConclusionsDonor lungs develop a detectable and discriminatory pro-inflammatory signature in perfusate during EVLP. Blocking the IL-1β pathway during EVLP may reduce endothelial activation and subsequent neutrophil adhesion on reperfusion; this requires further investigation in vivo.

Current state of ex-vivo lung perfusion.

The purpose of the current report is to review the ex-vivo peer-reviewed literature published in the last 5 years and to summarize the findings. Encouraging data have been published by several centers utilizing ex-vivo lung perfusion (EVLP) as a means to identify viable grafts from the high-risk donor pool. The outcomes of transplanted lungs that were initially declined because of poor quality, but reevaluated with ex-vivo perfusion, are equivalent to standard criteria donor lungs. Further, research reports have emphasized the role of ex-vivo perfusion as a platform to improve graft quality and reduce the injurious effects of ischemia-reperfusion. Over the last 10 years, EVLP has proved its value as a reassessment tool to increase donor utilization. As short- and long-term data demonstrate the safety of EVLP, its use as a therapeutic platform is emerging, along with the promise of a new era in lung transplantation.

(741) - Impacts of Donor Smoking History and Age on Lung Transplant Survival

s S271 Purpose: Extended criteria donor lungs are increasingly used for transplantation. The arterial partial pressure of oxygen of donors at organ offer is widely regarded as an important marker for the quality and transplantability of the lung. More precise, a PaO2/FiO2 300 mmHg. Methods: 464 consecutive lung transplantations performed at our centre between April 2010 and October 2013 were analyzed. Outcome parameters included overall survival, hospital mortality and correlation of duration of postoperative ventilation. Results: 70 patients received grafts of donors with PaO2/FiO2 300. There were no significant recipient differences in age (45.6±0.8 vs. 48.3±1.5 yrs, p= 0.12) or sex (51% vs. 53% male). Postoperative parameters of the recipients including duration of mechanical ventilation time (14 [2-1619] hours vs. 27 [2-4077] hours; p= 0.14), intensive care stay (2 [1-49] days vs. 3 [3-203] days; p= 0.12) or total hospital stay (23 [11-199] days vs. 26 [11-224] days; p= 0.54) showed no significant differences between both groups. Also, hospital mortality (4.2% vs. 5.1%; p= 0.78) did not differ. Overall survival of the recipients showed no significant difference (p= 0.56). Further differentiation into subgroups according to donor oxygenation (PaO2/FiO2 300) showed no significant difference in survival (p= 0.52). Donor characteristics showed longer duration of mechanical ventilation in the group with a PaO2/FiO2< 300 (6.9±0.6 days vs. 5.3±0.2 days; p= 0.01). Correlation analysis showed no significant correlation between donor PaO2/FiO2 and recipient postoperative ventilation time (p= 0.49) or total hospital stay (p= 0.12). Conclusion: Donor lungs showing low arterial PaO2 values at offer can safely be used for transplantation, if a structural damage to the organ is excluded during retrieval. We conclude that a further increase of usage of donor organs that might have a compromised oxygenation capacity before retrieval should be attempted.

Extended criteria donor lungs and clinical outcome: Results of an alternative allocation algorithm

Despite the scarcity of donor lungs, most potential donor organs are not offered by organ procurement organizations or are turned down by transplant centers because no suitable recipient is found according to regular allocation. Although extended criteria donors (ECDs) have recently been considered by many programs, the lung utilization rate remains < 30% in most countries. The allocation policy of Eurotransplant for donor lungs that have been turned down for donor-related medical reasons by 3 centers is to attempt a rescue offer, for which centers choose the recipients themselves. At Hannover Medical School we systematically divert these organs to more stable recipients to avoid adverse transplant outcomes. We follow up on these transplants and compare them with those following regular allocation. This study is an analysis of all organ offers and corresponding recipients at our center during the period from January 2010 to August 2011. A total of 183 lung transplantations were performed, 111 regular donor lung offers were accepted for their intended recipient, whereas a total of 72 rescue lung offers, including all extended criteria donors, were accepted for recipients selected by our center. Donor characteristics differed between the 2 groups accordingly. Median age of ECD organ donors was significantly higher than that of regular donors (46.0 [IQR 21] vs 40.0 [IQR 22] years, p = 0.02). Donor mechanical ventilation time did not differ (3.5 ± 4.8 vs 3.0 ± 4.0 days, p = 0.33, not statistically significant [NS]). Donor oxygenation ratio (PaO2:FIO2) at time of organ offer was significantly lower (398.3 ± 110.3 vs 423.0 ± 97.6 mm Hg, p = 0.02). Recipients of rescue allocation organs were older than regularly selected recipients (53.7 ± 11.7 vs 46.7 ± 15.4 years, p = 0.0003), needed a shorter time for mechanical ventilation post-operatively (19.5 ± 306.6 vs 68.5 ± 718.8 hours, p = 0.02), and had shorter hospital stays (24.0 ± 23.4 vs 47.0 ± 43.4 days, p > 0.0001). Intensive care stay length did not differ significantly (2.0 ± 14.5 vs 5.0 ± 23.7 days, p = 0.21 [NS]). Post-operative survival up to 27 months after transplantation was not worse in recipients receiving rescue allocation when compared with standard allocation lung offers (81.62% vs 80.76%, p = 0.89 [NS]). The pre-operative status of the 2 recipient cohorts differed considerably, as indicated by the standard allocation group consisting of 65.8% "high-urgency" (HU)-listed patients, whereas the rescue offers were used for only 11.1% of HU-listed recipients, reflecting our center's policy. Rescue allocation donor lungs can be used safely for transplantation and therefore salvaged for the donor pool. The data support our policy of accepting marginal donor lungs for stable recipients. This practice leads to very good overall survival.

Extended Criteria Donors; a Safe Way To Expand the Lung Donor Pool?

Purpose Although the worldwide need to expand the lung donor pool, 75 % of multi-organ donors are discarded for lung transplantation (LTx). Herein, we report the outcome of liberalizing standard lung donor criteria. Methods and Materials All effective heart-beating lung donors within our hospital network between 2000 and 2010 (n=449) were classified as standard (SCD, n=284) or extended (ECD, n=149) criteria donors according to age (>55years), P/F ( Results Short-term outcome demonstrated significant differences in ICU stay ( p =0.03), PGD T12 ( p =0.003), T24 ( p =0.009) and T48 ( p =0.03) but not for time to extubation ( p =0.28). No significant differences were seen in long-term outcome like acute rejection ( p =0.84), chronic rejection ( p =0.18) and 10-year survival ( p =0.33, Figure A). Adding donor smoking status resulted in similar findings. Significant differences remained in short-term outcome like PGD T12( p =0.001), T24( p =0.001) and T48( p =0.001), extubation time ( p =0.04), ICU stay ( p =0.02) was observed. While no differences were found for long-term outcome as acute rejection ( P =0.85), chronic rejection ( p =0.54) and survival ( p =0.72, Figure B). Conclusions Although, transplanting ECD lungs has an impact on the early post-operative outcome after LTx, even more pronounced for lungs from smokers, liberalization of lung donor criteria did not negatively influence long-term outcome after LTx.

Normothermic perfusion of donor lungs for preservation and assessment with the Organ Care System Lung before bilateral transplantation: a pilot study of 12 patients

Cold flush and static cold storage is the standard preservation technique for donor lungs before transplantations. Several research groups have assessed normothermic perfusion of donor lungs but all devices investigated were non-portable. We report first-in-man experience of the portable Organ Care System (OCS) Lung device for concomitant preservation, assessment, and transport of donor lungs. Between Feb 18, and July 1, 2011, 12 patients were transplanted at two academic lung transplantation centres in Hanover, Germany and Madrid, Spain. Lungs were perfused with low-potassium dextran solution, explanted, immediately connected to the OCS Lung, perfused with Steen's solution supplemented with two red-cell concentrates. We assessed donor and recipient characteristics and monitored extended criteria donor lung scores; primary graft dysfunction scores at 0, 24, 48, and 72 h; time on mechanical ventilation after surgery; length of stays in hospital and the intensive-care unit after surgery; blood gases; and survival of grafts and patients. Eight donors were female and four were male (mean age 44·5 years, range 14-72). Seven recipients were female and five were male (mean age 50·0 years, range 31-59). The preharvest donor ratio of partial pressure of oxyen (PaO(2)) to fractional concentration of oxygen in inspired air (F(I)O(2)) was 463·9 (SD 91·4). The final ratio of PaO(2) to F(I)O(2) measured with the OCS Lung was 471·58 (127·9). The difference between these ratios was not significant (p=0·72). All grafts and patients survived to 30 days; all recipients recovered and were discharged from hospital. Lungs can be safely preserved with the OCS Lung, resulting in complete organ use and successful transplantation in our series of high-risk recipients. In November, 2011, we began recruitment for a prospective, randomised, multicentre trial (INSPIRE) to compare preservation with OCS Lung with standard cold storage. TransMedics and German Federal Ministry of Education and Research.

Defining an extended criteria donor lung: an empirical approach based on the Eurotransplant experience1

The aim of this study was to design and validate a lung donor score that reflects experts' perceived risk of allograft failure. All lung donors reported to Eurotransplant from 1999 to 2007 [N=6080] were used to create a lung donor score. Based on observed discard rates and using multivariate regression, points were assigned for six preprocurement donor variables. Donors reported in 2008 were used to validate the score [N=751]. All the six factors significantly predicted discard; as an example, the following donor with points: age 55-59years: 2; compromised history: 4; smoking: 2; shadow on chest X-ray: 2; purulent secretion during bronchoscopy: 2; and Pao(2) /Fio(2) ratio below 300mmHg: 3. Discard rates for donors with a lung donor score of 6 points (class 1) was 18%, while 36% and 54% of the donors with a score of 7-8 (class 2) and 9+(class 3) were discarded (P<0.001), respectively. In addition, the donor lung score was significantly associated with 1-year survival: class 1: 91%; class 2: 80%; and class 3: 72% (P=0.017). The lung donor score accurately reflects the likelihood of organ acceptance and predicts patient mortality, and its application at time of donor reporting may facilitate donor risk assessment and patient selection.

The number of lung transplants can be safely doubled using extended criteria donors; A single-center review

Relaxing the standard lung donor criteria may significantly increase the reported 15% organ yield but post-transplant recipient outcome should be carefully monitored. Charts from all consecutive deceased organ donors within our hospital network were reviewed over a 2-year period. Reasons for lung refusals and number of lungs transplanted were analysed. Hospital outcome including early recipient survival was compared between standard- and extended criteria donors. Out of 283 referrals, 164 (58%) qualified as donor of any organ. The majority (65.9%) of these effective donors were declined for lung donation because of chest X-ray abnormalities (20%), age >70 years (13%), poor oxygenation (10%), or aspiration (9%). Out of 56 (34.1%) accepted lung donors, 50 transplants were performed at our center, 23 from standard criteria donors versus 27 from extended criteria donors. There were no significant differences in hospital outcome and in early survival between lung recipients from both donor groups. Lung acceptance rate (34.1%) in our donor network is 10-20% higher than reported figures. The number of lung transplants in our center doubled by accepting extended criteria donors. This policy did not negatively influence our results after lung transplantation.

173: Normothermic Human Ex Vivo Lung Perfusion (EVLP) for Improved Assessment of Extended Criteria Donor Lungs for Transplantation

Expected Completion Date: March 2009. Sponsor of the trial: VITROLIFE. Summary of Objectives: 1) To examine the feasibility and safety of ex vivo perfusion of extended criteria donor lungs prior to transplantation and 2) To determine if ex vivo evaluation of extended donor lungs prior to the decision of transplantation will increase utilization rates and improve outcomes after lung transplantation.

Lung Donor Selection and Management

Lung transplantation is still limited by the shortage of suitable donor organs. This results in long waiting times for listed patients with a substantial risk (10-15%) of dying before transplantation. All efforts to increase donor awareness through legislation, public campaigns, and training of transplant coordinators and medical ICU staff should be encouraged. Only a minority of cadaveric donors meets the preset ideal lung donor criteria, leaving many transplantable lungs untouched. Donor lung utilization can be further improved by careful selection of extended criteria donors, by active participation of transplant teams in donor management, and by verifying as often as possible the quality of lungs in the donor hospital by a member of the transplant team. This article aims to update the current evidence from the literature to identify and select potential lung donors and to manage cadaveric donors to maximally increase the organ yield for lung transplantation.

Análise das características dos pulmões disponibilizados para transplante no Estado de São Paulo

Objetivos: Analisar a taxa de aproveitamento de pulmões disponibilizados em SãoPaulo em 2006, bem como caracterizar o perfi l dos doadores de pulmão deste período. Métodos: Estudo retrospectivo de 497 prontuários de doadores de pulmão, no período de jan/2006a dez/2006. Resultados: Dos 497 prontuários analisados, 149 (30%) não tiveram os pulmõesdoados, sendo excluídos do estudo. Dos 348 doadores eleitos para o estudo, 56,9% eram dosexo masculino, com idade média de 37,4±16,1anos. As principais causas da morte cerebralforam: AVC (40,5%), TCE (34,2%) e HSA (10,9%). A grande maioria recebia drogas vasoativas (90,5%), sendo que 13,5% haviam apresentado parada cárdio-respiratória. Do ponto de vistainfeccioso, o leucograma médio foi de 15008 ± 6467mm3, 67,8% recebiam antibioticoterapia e26,1% apresentavam infecção pulmonar. Quase 40% dos doadores apresentavam alteraçõesradiográfi cas. Apenas 4,9% dos doadores foram aceitos, representando 28 pulmões (taxa deaproveitamento de órgãos de 4,0%). Os motivos de recusa foram: alteração gasométrica (30,1%),infecção (23,7%) e distância (10,9%). Conclusão: A taxa de aproveitamento de pulmões emnosso meio é baixa. Além disso, mais de 50% das recusas deveram-se a gasometria arterialinadequada e infecção pulmonar. Aliar melhor cuidado ao potencial doador à menor rigidez noscritérios de seleção poderia aumentar a utilização dos órgãos doados.

Extended donor criteria in lung transplantation: Impact on organ allocation

Some reports have documented a higher early mortality with the use of extended criteria donors in lung transplantation. None have evaluated how outcomes compare with the use of these organs for single and bilateral transplantation or whether this practice results in a higher incidence of early bronchiolitis obliterans syndrome. We performed a retrospective review of case notes, intensive therapy unit database, and donor details. Between January 1, 2000, and December 31, 2004, 201 patients underwent lung or heart-lung transplantation. Eighty-three (41.3%) patients received organs deemed marginal on the basis of at least one of the following criteria: donor age greater than 55 years, duration of ventilation greater than 5 days, purulent secretions or inflammation at bronchoscopy, smoking of 20 or more cigarettes per day, abnormality on chest roentgenogram, or PO2/fraction of inspired oxygen ratio of less than 300 mm Hg immediately before donor organ procurement. Recipients of marginal lungs had a higher incidence of severe (grade 3) primary graft dysfunction (43.9% vs 27.4%, P = .015) and 90-day organ-specific mortality (15.7% vs 5.1%, P = .012). Bilateral transplantation carried a significantly higher 30-day mortality if performed with marginal organs (17.0% vs 2.7% with standard donor organs, P = .005). Thirty-day mortality was not significantly different for the transplantation of single marginal or standard donor lungs. Cumulative survival and survival free of bronchiolitis obliterans syndrome was not affected by marginal donor status. Transplantation of extended criteria donor lungs leads to a higher incidence of primary graft dysfunction. Bilateral transplantation with these organs seems to confer less reserve, resulting in a higher early mortality rate. Medium-term functional outcome is, however, not adversely affected by the relaxation of donor criteria.

Influence of Donor Characteristics on Outcome After Lung Transplantation: A Multicenter Study

The liberalization of lung-donor criteria and the use of marginal donors have been advocated to face the current shortage of donors in lung transplantation. However, the impact of donor characteristics on the outcome of lung transplantation is still largely unknown. We aimed to determine, on a large cohort of patients, the effect of donors characteristics on short- and long-term outcome of lung transplantation Between 1988 and 1998, a total of 785 adult patients underwent single-lung transplantation (n = 270), bilateral-lung transplantation (n = 251), and heart-lung transplantation (n = 264) in 7 centers in France. We constructed several multivariate models to assess the relationship between donor characteristics and early gas exchange, duration of mechanical ventilation, and long-term survival after lung transplantation. Among donor characteristics, donor gas exchange before harvest was found to be significantly associated with recipient early gas exchange, duration of mechanical ventilation, and long-term survival after adjustment for potential confounding variables. Moreover, nonlinear modeling showed a steep increase in the relative risk of death when donor PaO2/FiO2 before harvest was below 350 (hazard ratio 1.43; 95% confidence interval 1.10-1.85; p = 0.01). Donor and recipient sex mismatch were also found to be significantly associated with long-term survival. Although liberalization of lung-donor criteria may be considered to overcome the shortage of lung donors, our data suggest that the violation of the gas-exchange criterion should be avoided.

Extended donor criteria for lung transplantation—a clinical reality

Standard lung donor criteria have been established on opinions and individual experiences rather than on existing evidence. Since the scarcity of donor organs is one of the major limitations to lung transplantation, extension of donor lung criteria might considerably increase the donor pool. This study therefore evaluates the outcome, achieved with the use of extended donors versus standard donors and aims to redefine lung donor criteria. We performed a retrospective analysis of 98 consecutive primary lung transplantations from 94 donors from 1/2001 to 12/2002. Donors were classified as extended if they fulfilled at least one criteria: age >55 years, PaO(2) at FiO(2)/PEEP 5 <300mmHg, tobacco history >20 pack years, inhalative drug abuse, presence of infiltration on chest X-ray or purulent secretions at bronchoscopy. Recipients were stratified in two groups according to whether they received a 'standard' or 'extended' organ. Postoperative complications, extubation time, ICU and hospital stay and survival were compared. Twenty-three (24.5%) donors were extended. Twenty-six recipients (26.55%) received organs from extended donors. Differences in intubation times (12+/-2 days standard vs. 14+/-5 days extended, P=0.70), ICU stay (16+/-2 days standard vs. 18+/-5 days extended, P=0.74) and hospital stay (38+/-4 days standard vs. 40+/-6 days extended, P=0.71) were not statistically significant. Postoperative bleeding rates were comparable (n=14 standard vs. n=3 extended) as well as bronchial anastomotic complications (n=7 standard vs. n=3 extended). Three months survival was 88.89% in the standard group vs. 92.31% in the extended group. One year survival is comparable as well with 81.94 vs. 84.62%, respectively. The use of lung donors who fail to meet standard criteria does not impair short and medium term results compared to standard lung donors. The impact on long term development of BOS has yet to be evaluated. The strict application of standard lung donor criteria excludes a considerable number of lungs potentially suitable for transplantation, thus liberalisation of donor criteria might help to overcome donor shortage.

Should lungs from donors with severe acute pulmonary embolism be accepted for transplantation? the Hannover experience

Lung transplantation has evolved to an accepted treatment modality for patients suffering from end-stage lung disease. The number of listed patients waiting for a lung transplant is dramatically higher than the number of available donor organs, which contributes to a 1-year mortality on the waiting list of approximately 20% and of 40% after 2 years of listing. Many strategies aiming for an increase of donor organs have been discussed controversially and are partially under clinical examination, such as the utilization of lungs from non–heartbeating donors or the concept of living-related lung transplantation. Other approaches to the problem are even more experimental, such as pulmonary xenotransplantation. During the 2003 annual meeting, The International Society for Heart and Lung Transplantation discussed the issue of redefining current lung donor criteria and the concept of using marginal donor organs for selected recipients in a main session. Many groups presented their outcomes following lung transplantation using lungs from donors who were heavy smokers, from donors with onset of fatal asthma, or from elderly donors up to 77 years of age. One major consensus of this intense discussion, however, was that some donors are still considered as inadequate for lung donation, such as patients who show signs of severe pneumonia or aspiration as well as those who died from fulminant pulmonary embolism. Here, we report on 3 cases in which lung grafts from patients with fatal severe acute pulmonary embolism were successfully transplanted. We further describe a novel strategy of in situ retrograde lung flush perfusion that we are routinely using in our clinical program now, which is of special importance for lung graft retrieval from donors with acute pulmonary embolism.

IL-1β in broncho-alveolar lavage is a non-invasive predictor of the viability of the pulmonary graft from the non-heart-beating donor

donors have focused on short-term (1 year) outcome. We previously published the 1-year outcomes and short-term complications associated with the use of extended donors. We now present data on follow-up of these patients three years after transplantation. Methods: One hundred thirteen patients underwent lung transplantation at our institution between 1996 and 1999. Patients were categorized as receiving lungs from either ideal or extended donors. An extended donor was defined as having any one of the following: donor age 55 years; tobacco history 20 pack years; radiographic infiltrates; mechanical ventilation 5 days; or donor use of inhaled drugs (cocaine or marijuana). The groups were compared for the development of bronchiolitis obliterans syndrome (BOS), the severity of BOS and 3-year post-transplant survival. Results: Sixty-one (54%) patients received lungs from ideal donors and 52 (46%) patients received lungs from extended donors. BOS developed in 6/61 (10%) patients in the ideal group and 10/52 patients (20%) in the extended group (p ns). The mean time to development of BOS was 22 13 months in the ideal group compared to 17 12 months in the extended group (p ns). Three patients (5%) in the ideal group developed BOS grade 2 or higher compared to 7/52 (13%) patients in the extended group (p ns). There was no difference in the 3-year survival between the groups (44%vs.60%; p ns) Conclusions: The use of extended donors is not associated with the development of BOS or increased mortality at three years after transplantation. This data supports reevaluation of the current guidelines for lung donor criteria.

Donor Criteria in Lung Transplantation: An Issue Revisited

The availability of suitable lung donors is the major limitation to increasing the number of lung transplants performed. Donor criteria developed early in the lung transplant era have not been rigorously evaluated. Each of the "standard" lung donor criteria currently in use should be challenged by obtaining, analyzing, and using multicenter data from a well-designed database. Only in this way will our understanding of appropriate lung donor criteria advance and the pool of lungs available for transplantation increase.