Lung donors selection criteria: a review

Lung transplantation has had increasing success worldwide and it became an acceptable treatment modality in end-stage pulmonary diseases. The insufficient supply of donor lungs, resulting in prolonged waiting time, and the significant rise of patients on the waiting list, have forced the most experienced transplantation centers to redefine the acceptable lung donor criteria including marginal allografts. Existing standard lung donor criteria have been established in the first period of lung transplantation activity, based mainly on opinions and individual experiences rather than on existing evidences: the paucity of donors may be also explained by the rigid application of these criteria. The quality of donor organs has a significant impact on early and long-term recipient outcome. Recent studies have demonstrated that the use of marginal donors did not affect early and late recipient outcome, and significantly increased the number of transplants performed. The aim of this paper is to review how the main lung donor selection criteria have been changed and how they influence the recipient outcome.     

Non-heart-beating donors in thoracic transplantation.

Access to lung transplantation is severely limited by a scarcity of suitable donors, resulting in increasing numbers of deaths on the heart and lung transplant waiting lists, and strict selection criteria for recipients. Unlike some other solid organs, the lung may be ideally suited to retrieval for transplant following substantial intervals after circulatory arrest. This may be because lung parenchymal cells do not rely on perfusion for cellular respiration. This review outlines the relevant published experimental data that addresses the concept that lungs might be suitable for transplant even if retrieved from non-heart-beating donors (NHBDs), and the small published clinical experience with NHBDs as lung donors. Aspects of reperfusion injury in this setting are reviewed. The prospect of heart transplant from NHBDs is addressed. The impact of the routine use of NHBDs on lung transplantation is discussed.     

Current techniques of organ procurement and organ conservation

Since organ transplantation became a standard procedure in medicine, some interdisciplinary discussion has evolved around the availability of organs for transplantation. The shortage of available donors leads to numerous deaths on waiting lists where heart, lung and liver disease is concerned. Patients on dialysis spend years waiting for a suitable cadaveric graft. The shortage of organs has widened not only the selection criteria for cadaveric donors and the optimization of procurement but also has led to the increased acceptance of relatives and friends as living donors for kidneys, parts of the liver and maybe in the future of the lung. It has to be decided in which direction one wants to influence the discussion about the retrieval of an adequate number of organs for our waiting patients.     

Outcomes of extended donor lung recipients after lung transplantation

BACKGROUND: Lung transplantation is currently limited by the number of suitable donor organs. Many lung-transplant programs use lungs that do not meet the formal criteria for acceptability; however, the immediate and long-term consequences of this approach remain unclear. METHODS: We performed a retrospective cohort study of all patients who underwent lung transplantation at the Columbia University Medical Center from July 2001 to July 2003. We assessed the outcomes of recipients of extended donor lungs compared with those of recipients of optimal donor lungs after adjusting for confounding variables. RESULTS: Fifty-one patients underwent lung transplantation, of which 27 (53%) received extended donor lungs. Recipients of extended donor lungs had fewer intensive care unit-free days at 30 days (P=0.002) and a longer time to hospital discharge (P=0.007) than did recipients of optimal donor lungs. Extended donor recipients also had lower forced expiratory volume in 1 second % predicted at 1 year than did optimal donor recipients (P=0.03). There were no differences in the 30-day or longer-term survival of extended and optimal donor lung recipients. CONCLUSIONS: Recipients of extended donor lungs have a longer intensive care unit course, a prolonged hospital stay, and lower pulmonary function at 1 year than recipients of optimal lungs. Despite these differences, survival is similar between the two groups. The criteria for the optimal lung donor should be re-evaluated considering the current shortage of acceptable organs. Although some outcomes may differ with the use of extended donor lungs, the clinical impact of these differences should be assessed in future prospective multicenter studies.     

Extended donor criteria for lung transplantation--a clinical reality.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Advances in organ preservation for transplantation

Organ transplantation provides the best available therapy for a myriad of medical conditions, including end‐stage renal disease, hepatic failure and type I diabetes mellitus. The current clinical reality is, however, that there is a significant shortage of organs available for transplantation with respect to the number of patients on organ waiting lists. As such, methods to increase organ supply have been instituted, including improved donor management, organ procurement and preservation strategies, living organ donation, transplantation education and the increased utilization of donation after circulatory death and expanded criteria donors. In particular, especially over the last decade, we have witnessed a significant change in the way donor organs are preserved, away from static cold storage methods to more dynamic techniques centred on machine perfusion (MP). This review highlights the current state and future of organ preservation for transplantation, focusing on both abdominal and thoracic organs. In particular, we focus on MP preservation of renal, hepatic, pancreatic, cardiac and lung allografts, also noting relevant advances in Australasia. MP of organs after procurement holds considerable promise, and has the potential to significantly improve graft viability and function post‐transplantation, especially in donors in whom acceptance criteria have been expanded.     

Survival benefit of lung transplantation for patients with idiopathic pulmonary fibrosis

OBJECTIVE: Although lung transplantation is viewed as an acceptable option for patients with end-stage idiopathic pulmonary fibrosis, the survival benefit of this approach is still debated. This study examined whether there was a survival benefit of lung transplantation in a cohort of patients referred to our transplant center with a diagnosis of idiopathic pulmonary fibrosis according to American Thoracic Society criteria. METHODS: Forty-six patients accepted for lung transplantation during a 12-year period with a diagnosis of idiopathic pulmonary fibrosis form the basis of this study. Survival benefit offered by lung transplantation was assessed using Cox proportional-hazards modeling, with patients on a waiting list as the control group. RESULTS: Twenty-eight patients underwent lung transplantation (27 single and 1 double), 16 patients died while waiting, and 2 patients remained on the active waiting list. Diagnosis of idiopathic pulmonary fibrosis was made on histologic examination of the explanted lung or lung biopsy before lung transplantation. There was a pattern of usual interstitial pneumonia in 31 cases (67%). The 15 remaining patients fulfilled all American Thoracic Society criteria for idiopathic pulmonary fibrosis. The median waiting time for organs was 51 days. Survival after lung transplantation was 79.4% at 1 year, 63.5% at 2 years, and 39% at 5 years. The multivariable analysis showed that lung transplantation reduced the risk of death by 75% (95% confidence interval, 8%-86%; P =.03) after adjustment on potential confounding variables. CONCLUSIONS: Lung transplantation is effective in improving the survival of selected patients affected by idiopathic pulmonary fibrosis.     

Management to optimize organ procurement in brain dead donors

The demand for donor organs continues to exceed the number of organs available for transplantation. Many reasons may account for this discrepancy, such as the lack of consent, the absence of an experienced coordinator team able to solve logistical problems, the use of strict donor criteria, and suboptimal, unstandardized critical care management of potential organ donors. This has resulted in efforts to improve the medical care delivered to potential organ donors, so as to reduce organ shortages, improve organ procurement, and promote graft survival. The physiological changes that follow brain death entail a high incidence of complications jeopardizing potentially transplantable organs. Adverse events include cardiovascular changes, endocrine and metabolic disturbances, and disruption of internal homeostasis. Brain death also upregulates the release of pro-inflammatory molecules. Recent findings support the hypothesis that a preclinical lung injury characterized by an enhanced inflammatory response is present in potential donors and may predispose recipients to an adverse clinical prognosis following lung transplantation. In clinical practice, hypotension, diabetes insipidus, relative hypothermia, and natremia are more common than disseminated intravascular coagulation, cardiac arrhythmias, pulmonary oedema, acute lung injury, and metabolic acidosis. Strategies for the management of organ donors exist and consist of the normalization of donor physiology. Management has been complicated by the recent use of 'marginal' donors and donors of advanced age or with 'extended' criteria. Current guidelines suggest that the priority of critical care management for potential organ donors should be shifted from a 'cerebral protective' strategy to a multimodal strategy aimed to preserve peripheral organ function.     

The contribution of donor management and modified cold blood lung perfusate to post-transplant lung function.

BACKGROUND: Donor organ availability remains the major limiting factor in the treatment of patients with end-stage lung disease by lung transplantation. Maximising the use of available organs is therefore crucial. Details available at the time of organ referral may give a misleading impression of their quality. Intensive donor management may improve the quality of the organs thereby improving the quality of the outcome. METHODS: We performed 56 heart-lung and 5 double lung transplants between November 1990 and September 1993; 49 had adequate documentation for analysis. All organs were preserved with modified cold blood solution with an ischemic time of 197 (117-297) minutes. Assessment of lung function post-implantation was performed using an acute lung injury score as this gives a more accurate indication of overall lung function. Donors were treated intensively by bronchoscopy, optimal fluid management and appropriate lung expansion. RESULTS: Careful management improved donor quality so that the alveolar-arterial oxygen gradient fell significantly from 185 (+/-20) mmHg at arrival to 80 (+/-11) mmHg (p < .0001) immediately prior to harvesting 190 minutes later. This improvement was maintained following harvesting using the modified cold blood preservation solution so that lung injury was assessed as "mild" according to the acute lung injury criteria post-transplantation. There was one instance of primary lung failure following transplantation which was neither related to the quality of the organ at harvesting nor to the method of lung preservation. CONCLUSIONS: Intensive donor management significantly improves the quality of donor organs, providing an improvement in immediate post-transplantation lung function. This improvement is maintained using modified cold blood lung preservation solution.     

Non–heart-beating donors (then) and donation after cardiac death (now)

In the 1960s and 1970s, before the acceptance of brain death, donated organs were obtained from non–heart-beating donors. Today, this type of donor is referred to as a donor after cardiac death (DCD). After the acceptance of brain death criteria, most of the organs for transplantation were obtained from heart-beating donors. However, because of the shortage of brain-dead heart-beating donors in the 1980s, Maastricht surgeons started using organs obtained from DCD. Subsequently, they defined 4 different categories of non–heart-beating donors. In the United States, DCD donation has only recently gained widespread use. In this article, we present a historical overview of DCD donation; examine current practices for organ preservation and outcomes for kidney, kidney-pancreas, liver, and lung transplantation performed using organs obtained from DCD donors; and reported to the Organ Procurement and Transplantation Network/United Network for Organ Sharing database.     

Successful transplantation of marginally acceptable thoracic organs.

OBJECTIVE: This study evaluates the efficacy of personally inspecting marginal thoracic organ donors to expand the donor pool. SUMMARY BACKGROUND DATA: The present donor criteria for heart and lung transplantation are very strict and result in exclusion of many potential thoracic organ donors. Due to a limited donor pool, 20-30% of patients die waiting for transplantation. METHODS: The authors have performed a prospective study of personally inspecting marginal donor organs that previously would have been rejected by standard donor criteria. RESULTS: Fourteen marginal hearts and eleven marginal lungs were inspected. All 14 marginal hearts and 10 of the marginal lungs were transplanted. All cardiac transplant patients did well. The mean ejection fraction of the donor hearts preoperatively was 39 +/- 11% (range 15-50%). Postoperatively, the ejection fraction of the donor hearts improved significantly to 55 +/- 3% (p < 0.002). Nine of the ten lung transplant patients did well and were operative survivors. Our donor pool expanded by 36% over the study period. CONCLUSIONS: The present donor criteria for heart and lung transplantation are too strict. Personal inspection of marginal thoracic donor organs will help to maximize donor utilization.     

Pediatric lung transplantation as standard of care

For infants, children, and adolescents with progressive advanced lung disease, lung transplantation represents the ultimate therapy option. Fortunately, outcomes after pediatric lung transplantation have improved in recent years now producing good long‐term outcomes, no less than comparable to adult lung transplantation. The field of pediatric lung transplantation has rapidly advanced; thus, this review aims to update on important issues such as transplant referral and assessment, and extra‐corporal life support as “bridge to transplantation”. In view of the ongoing lack of donor organs limiting the success of pediatric lung transplantation, donor acceptability criteria and surgical options of lung allograft size reduction are discussed. Post‐transplant, immunosuppression is vital for prevention of allograft rejection; however, evidence‐based data on immunosuppression are scarce. Drug‐related side effects are frequent, close therapeutic drug monitoring is highly advised with an individually tailored patient approach. Chronic lung allograft dysfunction (CLAD) remains the Achilles' heel of pediatric lung transplant limiting its long‐term success. Unfortunately, therapy options for CLAD are still restricted. The last option for progressive CLAD would be consideration for lung re‐transplant; however, numbers of pediatric patients undergoing lung re‐transplantation are very small and its success depends highly on the optimal selection of the most suitable candidate.     

Ex vivo evaluation of lungs from donation after cardiac death after recent cardiac surgery with cardiopulmonary bypass

Lack of suitable donor lungs is still a major limitation of lung transplantation. Extended donor acceptance criteria combined with innovative assessment tools can be used to expand the number of suitable organs. We describe a successful transplantation of lungs retrieved from a donor who had undergone aortic root replacement 9 days before donation after cardiac death. The lungs were assessed using ex-vivo lung perfusion.     

Anaesthesia for lobar lung transplantation from living donors

The shortage of cadaveric organs for transplantation has led to the increasing use of organs from living donors. Transplantation offers an increased length and quality of life for patients with end stage lung disease, although up to 30% of patients die before a cadaveric organ becomes available. This article summarizes the experience of lung transplantation from living donors at one United Kingdom centre. Donor and recipient selection will be outlined, and the perioperative management of both discussed. The ethical considerations of the use of lung tissue from living donors are also considered at length and common complications discussed.     

Two successful lung transplantations from a dialysis-dependent donor

The shortage of organs for lung transplantation has led to the growing use of "marginal" donors. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, recent data suggest that they may be suitable in selected cases. This article describes the successful transplantation of two lungs from a single donor who had been receiving long-term hemodialysis treatment. In the absence of other causes of pulmonary diseases, such as smoking or lung infection, lungs from dialysis-dependent patients may be acceptable for lung transplantation.     

Problems in donor lung evaluation for transplantation with regard to airway infection

The shortage of donor organs has been 1 of the major obstacles to solid organ transplantation. Typical lung donor criteria include clear lung field on chest radiograph, adequate oxygenation, acceptable lung compliance, and satisfactory bronchoscopic findings. To extend usage of available donors, liberalization of donor lung selection criteria has been facilitated, however, marginal donor lungs must be used with discretion, because donor lung injury, especially that related to infection, has a potential leading to early post-operative death of the recipient. From March 2000 to December 2006, we evaluated 15 braindead donors and at least 1 of the lungs from 9 donors was judged suitable for transplantation. One of 9 recipients developed severe pneumonia cased by carbapenems-resistant Pseudomonas aeruginosa possibly originating from the donor lungs, eventually leading to death. The chest radiograph and oxygenation of the donor had been satisfactory, however, a moderate amount of mucopurulent secretions was observed by bronchoscopic inspection and the donor had been given a cefozopran for 9 days before the procurement operation. Remaining 8 recipients were free from air-way infection in the early postoperative period. We discuss the status and problems of donor lung evaluation for transplantation with regard to donor lung infection.     

Expanding the donor pool: lung transplantation with donors 55 years and older

The scarcity of donor organs is one of the major limitations to lung transplantation. This has led to a progressive expansion of criteria for donor selection in lung transplantation. This study evaluated the outcome of recipients of lungs from donors >/=55 years. We performed a retrospective analysis of 212 consecutive lung transplantations. Recipients were divided into two groups, those receiving lungs from donors >/=55 years (older donor group) and those receiving lungs from donors <55 years (younger donor group). Recipient baseline characteristics, time in the intensive care unit (ICU), early mortality, and long-term survival (Kaplan-Meier) were compared between the groups. Forty-one donors (19%) were >/=55 years. Mean recipient age in the older donor group was higher than in the younger donor group (52 +/- 8 vs. 47 +/- 12 years; P = .015). Indication for transplantation did not differ between the groups. ICU stay was comparable between the two groups (6 +/- 12 vs. 7 +/- 11 days; P = .64). Actual 30-day mortality (10.8% vs. 6.4%; P = .32), 1-year mortality (17.1 vs. 19.6%; P = .50), and cumulative long-term survival (65% and 62% at 5 years, P = 1.00) did not differ between the older and younger donor group. This study indicated that transplantation of lungs from selected donors aged >/=55 years did not impair short-or long-term results. The use of lungs from elderly donors may help to increase the number of donor organs for lung transplantation.     

Lung transplantation

The supply of donor organs remains extremely limited, and improved methods of maintaining the lungs of potential donors to allow for transplantation must be developed. Currently the upper limit of donor lung ischemic even with our "best" preservation techniques is approximately 4 to 6 hours. Improved methods for preservation will increase the supply of suitable lungs and will considerably simplify the logistics of transplantation just as has occurred with liver transplantation. Efficient use of donor organs remains of paramount importance. We recently performed two single-lung transplants utilizing lungs from one donor. Likewise, there is no reason why a lung could not be sent to another center for transplantation if the harvesting group uses only one lung. Sufficient progress has been achieved to date to warrant continued application of lung transplantation for end-stage pulmonary disease. With increasing experience, one can anticipate refinement of techniques and broader application of these procedures. Single lung transplantation, initially restricted to patients with end-stage pulmonary fibrosis, has now been successfully applied to patients with emphysema, pulmonary hypertension, and other conditions. Although transplantation currently can offer real benefit only to a limited number of persons, it serves to create hope for many others. An additional benefit may prove to be the interest and attention that transplantation focuses on patients with end-stage lung disease and on the pathophysiology of chronic respiratory failure. Knowledge gained may ultimately result in the prevention of many of the disorders for which lung transplantation currently offers the only hope.     

Fatal diffuse pulmonary fat microemboli following reperfusion in liver transplantation with the use of marginal steatotic allografts

Organ shortage is a major cause of delayed liver transplantation and increased waitlist time. The level of donor steatosis is a significant determinant in organ selection. Scarcity of organs has led some programs to expand their acceptable criteria for the percentage of steatosis. We report two cases of liver transplantation of steatotic donor organs that resulted in mortality within hours from transplantation. Postmortem analysis showed evidence of diffuse pulmonary fat microemboli likely originating from the donor organ, with marked preservation reperfusion injury. The mechanism of diffuse fat microemboli in this setting and possible relationship to other perioperative syndromes (transfusion‐related lung injury, acute kidney injury, and postreperfusion syndrome) is discussed.     

Lung transplantation for emphysema

Great strides have been made in lung transplantation in the past two decades. Changes in technique, immunosuppression regimens, and treatment of infectious complications have led to improvements in survival and functional results. Current areas of discussion concern the use of single lung transplantation versus bilateral sequential lung transplantation and the criteria for allocating donor lungs. This article reviews the current state of lung transplantation for emphysema and provides insight from more than one decade of experience with Washington University's lung transplant program.