Lung Utilization Rates Research Articles

Ex Vivo Lung Perfusion

The number of patients listed for lung transplantation largely exceeds the number of available transplantable organs because of both a shortage of organ donors and a low utilization rate of lungs from those donors. A novel strategy of donor lung management – Ex vivo Lung Perfusion (EVLP) - that keeps the organ at physiological protective conditions have shown a great promise to increase lung utilization by reevaluating, treating, and repairing donor lungs prior to transplantation. Clinical trials using EVLP has shown the method to be safe and allow for reassessment and improvement in function from high risk donor lungs from both brain death and cardiac death donors prior transplantation. Pre-clinical studies have also shown a great potential of EVLP as a platform for the delivery of novel therapies to repair injured organs ex vivo and thus further improve lung transplantation outcomes. Herein we describe detailed steps for a successful EVLP procedure.

Strategies for safe donor expansion

The number of patients listed for lung transplantation largely exceeds the number of available transplantable organs because of both a shortage of organ donors and a low utilization rate of lungs from those donors. Two major innovations in recent years include the use of lungs from donations after cardiac death (DCD) and the use of ex-vivo lung perfusion (EVLP) to assess and improve injured donor lungs. DCD lung transplants now account for about 20% of lung transplants in many centres and outcomes after transplantation have been excellent with this source of donation. Clinical experience using EVLP has shown the method to be well tolerated and allow for reassessment and improvement in function from high-risk donor lungs. When these lungs were transplanted, low rates of primary graft dysfunction were achieved and long-term survival was comparable with standard transplantation. Preclinical studies have shown a great potential of EVLP as a platform for the delivery of novel therapies to repair injured donor lungs. A significant increase on the number of available lungs for transplantation is expected in the coming years with the wider use of DCD lungs and with organ-specific ex-vivo treatment strategies.

Donor risk prediction

This article reviews recent developments in the selection of the lung donor that aim to increase donor organ use. The scarcity of suitable donor organs continues to limit lung transplantation resulting in long waiting times and significant mortality for those patients awaiting transplantation. Strategies to expand the donor pool can substantially lift donor lung utilization rates from historically low levels of less than 15% to rates greater than 50% without inordinate risk of short-term or long-term complications. Numerical donor and recipient scores may have a significant role to play in measuring, comparing and contrasting lung transplant outcomes in future studies of donor variables. After considering the evolution of lung donor and recipient management practices, in 2013 the available evidence suggests that the traditional factors defining a lung as 'extended', do not actually compromise outcomes within the framework of current management strategies. Extended donor lungs are safe.

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.

Ex vivo lung perfusion (EVLP)

The number of patients listed for lung transplantation largely exceeds the number of available transplantable organs because of both a shortage of organ donors and a low utilization rate of lungs from those donors. A novel strategy of donor lung management—ex vivo lung perfusion (EVLP)—that keeps the organ at physiological protective conditions has shown a great promise to increase lung utilization by re-evaluating, treating, and repairing donor lungs prior to transplantation. A clinical trial using EVLP has shown the method to be safe and to allow for reassessment and improvement in function from high-risk donor lungs from both brain death and cardiac death donors prior transplantation. When these lungs were transplanted, low rates of primary graft dysfunction were achieved, and the early outcomes were similar to those with conventionally selected and transplanted lungs. Pre-clinical studies have also shown a great potential of EVLP as a platform for the delivery of novel therapies to repair injured organs ex vivo, and thus further increase the donor lung utilization rate.

Donor Selection and Management

This article reviews recent developments in the selection, assessment, and management of the potential lung donor, which aim to increase donor organ use. The scarcity of suitable donor organs continues to limit lung transplantation, but the situation is changing. An expanded donor pool, including the now widespread use of donation after cardiac death (DCD) lungs; the use of extended donor lungs; and the ability of ex vivo lung perfusion (EVLP) to evaluate and improve donor lungs are key initiatives. These strategies have substantially lifted donor lung utilization rates from historically low levels of less than 15% to rates greater than 50%. Indeed, since 2004 there has been an accelerated year-on-year increase in the number of lungs transplanted globally. Intermediate-term studies are now confirming that long-term outcomes are not being significantly compromised and that more individuals with terminal, symptomatic lung disease are being transplanted. It is now quite clear that many of the historical factors used to define a lung as "extended" do not actually produce significantly inferior outcomes. There has been a dramatic increase in research and clinical interest in donor lung assessment, management, and novel therapeutic strategies. The lessons learned are now being applied widely beyond the lung as researchers aim to increase availability and optimize other solid organs for transplantation.

The clinical potential of ex vivo lung perfusion

The number of patients listed for lung transplantation largely exceeds the number of available transplantable organs because of both a shortage of organ donors and a low utilization rate of donor lungs. Normothermic ex vivo lung perfusion (EVLP) is a method that maintains the organ in physiologically protective conditions outside the body during preservation, and shows great promise to increase utilization of donor lungs by allowing more accurate evaluation, as well as treatment and repair, of damaged donor lungs prior to transplantation. This article will cover the rationale, technical details and results of experimental and clinical studies with EVLP. The significant potential applications of EVLP in lung transplantation, lung regeneration and oncology are discussed.

Extracorporeal lung perfusion

The number of patients listed for lung transplantation largely exceeds the number of available transplantable organs because of both a shortage of organ donors and a low utilization rate of lungs from those donors due to injuries acquired during the process of brain death and intensive care unit (ICU) care. A novel strategy for donor lung preservation - ex-vivo lung perfusion (EVLP) - that keeps the organ at physiological protective conditions has shown great promise to increase lung utilization by reassessing, treating, and repairing injured donor lungs prior to transplantation. A first clinical trial using EVLP has shown the method to be safe and to allow for reassessment and improvement in function of lungs from high-risk donor lungs prior to transplantation. When these lungs were transplanted, low rates of primary graft dysfunction were achieved, and the early outcomes were similar to those with conventionally selected and transplanted lungs. Preclinical studies have shown a great potential of EVLP as a platform for the delivery of novel simple and advanced therapies to repair injured organs ex vivo and thus further increase the donor lung utilization rate. EVLP triggers a new era in lung transplantation. This method will allow for more and better organs to become available. Several experimental studies, clinical case reports, and a clinical trial have shown the safety of EVLP and the numerous potentials of EVLP.

Pulmonary Recruitment Protocol For Organ Donors: A New Strategy to Improve the Rate of Lung Utilization

Because lung transplantation is the only effective therapy for terminal respiratory failure, the demand for donor lungs has increased steadily. However, the number of donors has remained fairly constant over the years, which results in an increasing duration of waiting for lung transplantation. To overcome the lack of organs, various strategies have been developed by transplant centers including use of marginal donors. To increase the lung utilization rate in multiorgan donors, we implemented a simple lung recruitment protocol involving a brief period of controlled sustained inflation. In 2005, the lung utilization rate in the transplant program at our institution was only 20% in multiorgan donors. With the lung recruitment protocol, the rate of lung utilization for transplantation increased to 33%, in 2006, 24% in 2007, and 24% in 2008. Following the lung recruitment protocol, the arterial oxygen tension/fraction of inspired oxygen ratio increased to greater than 15% in more than 40% of donors. We were able to improve gas exchange sufficiently that as many as two-thirds of the lungs were suitable for transplantation. During the protocol, no complications were reported, and no patient became hemodynamically unstable, precluding organ procurement. We believe that optimization of multiorgan donor management with simple interventions may improve oxygenation, reducing the number of inadequate donor lungs and increasing the overall donor pool and organ availability.

Donor selection and management

The scarcity of suitable donor organs continues to limit lung transplantation, resulting in long waiting times and significant mortality for those patients listed for transplant. Strategies to expand the donor pool can substantially lift donor lung utilization rates from historically low levels of less than 20% to rates greater than 50%. This article reviews recent developments in the selection, assessment and management of the potential lung donor that aim to increase donor organ use. Close adherence to the originally published lung transplant donor acceptability criteria has historically restricted the number of donor lungs available for transplant. Important advances that aim to increase donor lung utilization include the use of donation after cardiac death lungs, cut-down lungs and expanded criteria lungs. Emerging diagnostic tools that predict how donor lungs will function after transplant are likely to facilitate selection of appropriate donor lungs significantly in the future. Optimal donor management should aim to maximize lung donation through aggressive donor management and consideration of the complete and expanded donor pool. However, long-term studies are required to validate such an approach and to confirm that long-term outcomes are not being compromised by the use of both traditional and nontraditional organ donors.

Perfil do doador de pulmão disponibilizado no estado de São Paulo, Brasil, em 2006

To analyze the rate at which lungs available for transplantation in the State of São Paulo in 2006 were utilized and to determine the lung donor profile in the same period. A retrospective study of 497 clinical charts of lung tissue donors from January to December of 2006. According to the clinical charts, lungs were not offered for transplant in 149 cases (30%), which were therefore excluded from the study. Among the 348 lung donors eligible for inclusion in the study, the mean age was 37.4 +/- 16.1 years, and 56.9% were males. The main causes of brain death among the donors were stroke (in 40.5%), skull-brain trauma (in 34.2%) and subarachnoid hemorrhage (in 10.9%). The great majority of these lung donors (90.5%) received vasoactive agents, and 13.5% presented cardiopulmonary arrest. The mean donor leukocyte count was 15,008 +/- 6,467 cells/mm(3), 67.8% of the donors received anti-bacterial agents, and 26.1% presented lung infection. Nearly 40% of the lung donors presented chest X-ray abnormalities. Only 4.9% of the lung donors were accepted, representing 28 lungs (allograft utilization rate of 4%). The causes for donor exclusion were gas exchange alterations (in 30.1%), infection (in 23.7%) and distance (in 10.9%). The lung utilization rate in the State of São Paulo is low when compared to mean rates worldwide. In addition, more than half of the donor pool was excluded due to altered gas exchange or pulmonary infection. The combination of better care of the potential donor and more flexible selection criteria could increase allograft utilization.

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.

Utilization of Donated Lungs in Australia: 1989–1997

Lung and heart-lung transplantation was first undertaken in Australia in the late 1980s and early 1990s. Although detailed data are available on Australian lung transplantation outcomes, little data are available regarding the utilization of donated lungs. This study examines donated lung utilization rates and considers various factors that may affect these rates. Australian donation and transplantation data were analyzed for the years 1989 through 1997. Results showed that 24% of overall donors were lung donors. The percentage of donors from whom at least 1 lung was transplanted increased from 6% in 1989 to 36% in 1997. Heart-lung transplantation rates changed little (2%-9%), whereas bilateral lung transplantation increased from 1% to 23% of donors. Single-lung donors accounted for 32% of lung donors in 1997. Uniform basic donor criteria and management guidelines, simple allocation mechanisms, and cooperative retrieval have evolved during this time. Close collaboration at the time of donation between units, coordinators, and ICUs has allowed early retrieval from well-managed donors.

Utilization of donated lungs in Australia: 1989-1997.

Lung and heart-lung transplantation was first undertaken in Australia in the late 1980s and early 1990s. Although detailed data are available on Australian lung transplantation outcomes, little data are available regarding the utilization of donated lungs. This study examines donated lung utilization rates and considers various factors that may affect these rates. Australian donation and transplantation data were analyzed for the years 1989 through 1997. Results showed that 24% of overall donors were lung donors. The percentage of donors from whom at least 1 lung was transplanted increased from 6% in 1989 to 36% in 1997. Heart-lung transplantation rates changed little (2%-9%), whereas bilateral lung transplantation increased from 1% to 23% of donors. Single-lung donors accounted for 32% of lung donors in 1997. Uniform basic donor criteria and management guidelines, simple allocation mechanisms, and cooperative retrieval have evolved during this time. Close collaboration at the time of donation between units, coordinators, and ICUs has allowed early retrieval from well-managed donors.