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Extended donor criteria in lung transplantation

Botha, Phil

Current Opinion in Organ Transplantation: April 2009 - Volume 14 - Issue 2 - p 206–210
doi: 10.1097/MOT.0b013e328326c834
Special commentary
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Purpose of review Despite improvements in respiratory care and lung transplant organ allocation algorithms, waiting lists continue to grow worldwide. Attempts at improving organ donation rates have generally had little impact on the increase in the number of transplants performed. Improved use of the available pool of cadaveric organ donors, therefore, represents one of few immediately available strategies to alleviate organ shortages.

Recent findings The once-strict lung donor selection criteria have, of necessity, been relaxed and, in many instances, this situation has been to no apparent detrimental effect on posttransplant outcome. There is, however, some evidence that extension of donor acceptability in some respects leads to poorer early outcomes, mainly by increasing the rate of early graft dysfunction. The extension of selection criteria to allow the maximum number of safe lung transplants, coupled with aggressive and appropriate donor management is, therefore, of particular current relevance to the lung transplantation community.

Summary Although the available evidence for and against the commonly used lung donor selection criteria leaves many questions unanswered, it can help decrease the large number of uncertainties that befalls the practice of lung donor selection and recipient matching.

Department of Cardiopulmonary Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom

Correspondence to Dr Phil Botha, MRCS, Department of Cardiothoracic Surgery, Freeman Hospital, High Heaton, Newcastle upon Tyne NE7 7DN, United Kingdom Tel: +44 191 233 6161; fax: +44 191 223 1152; e-mail: P.Botha@ncl.ac.uk

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Introduction

Current donor selection strategy may be severely limiting the wider application of lung transplantation. Although most series that explore the results of donor selection practice have been limited to single centres and, therefore, necessarily limited in size, reports from some larger institutions have shown that the current level of organ utilization in most of Europe and the United States falls far short of what can be achieved safely [1•]. The more widespread realization of a donor lung utilization rate of in excess of 50% would represent a doubling of current activity in many instances. The perceived risk of early graft failure, although related to certain donor variables in most series, is almost certainly overestimated routinely, which leads to the nonutilization of potentially suitable lungs. Intuitively, the physiology of the donor and the injury induced by brain-stem death must impose some limitations on the tolerance to subsequent ischaemia-reperfusion injury. Selection criteria defined during the early era of lung transplantation with the intention of selecting donors with lungs resistant to this injury have been necessarily strict [2]. Traditional lung transplant donor selection criteria are as follows:

  1. age ≤ 55 years;
  2. ABO compatibility;
  3. clear chest radiograph;
  4. paO2 ≥ 300 on fiO2 = 1.0, 5 cm H2O positive end-expiratory pressure (PEEP);
  5. tobacco history ≤ 20 pack years;
  6. absence of chest trauma;
  7. no evidence of aspiration/sepsis;
  8. no prior cardiopulmonary surgery;
  9. sputum Gram stain – absence of organisms;
  10. absence of purulent secretions at bronchoscopy.

Many centres have since documented a gradual relaxation of these criteria in an attempt to meet the burgeoning demand for donor lungs. Some limits to donor acceptability have however begun to emerge and as average donor age and comorbidity have increased, the interplay between donor diseases is becoming more important. While the wider application of ex-vivo assessment techniques are awaited, the maximal use of the available donor pool through accurate selection remains the only currently feasible method of optimizing donor utilization.

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Donor age

The mean age of cadaveric organ donors has increased by nearly 5 years since the early days of lung transplantation [3]. By necessity, most centres now routinely accept donors older than the original cut-off of 55 years. Although several reports have shown identical early outcomes with these donors [4,5••], others have found an increased early incidence of early graft dysfunction, even when a relatively conservative age cut-off of 45 years is used [6]. Concerns about reduced graft longevity have also been raised, with older donors (up to 77 years of age) showing a higher incidence of bronchiolitis obliterans syndrome [5••]. Advanced age has been shown to have a detrimental impact on organ function in cardiac [7], renal [8] and hepatic [9] transplantation, and, in biological terms, the lungs of older donors have been shown to produce lower levels of anti-inflammatory interleukin-10 [10]. This finding has been shown to correlate in turn with primary graft dysfunction and may be a plausible biological mechanism for the reduced resilience of older donor lungs to the effects of ischaemia-reperfusion injury. In contrast to earlier reports from the International Society for Heart and Lung Transplantation registry, recent cohorts demonstrate only a modest detrimental effect on survival at 1 and 5 years in recipients receiving lungs from older donors, which does not reach statistical significance [3]. It has been shown previously, however, that donor age interacts with other donor variables to predict poorer outcome. For instance, a prolonged ischaemic time has been shown to have a detrimental impact in transplantation of lungs from older donors [11]. At present, many units will accept the lungs from a donor in their 70s as long as there are no other adverse features, and, in the case of a young donor, will accept prolonged ischaemic times and poorer gas exchange, expecting the greater physiological reserve to allow recovery from ischaemia-reperfusion injury.

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Gas exchange

Although gas exchange is widely used as the sole objective assessment measure of donor lung function, its shortcomings are manifold. The injurious effects of brain-stem death on pulmonary capillary permeability result in the accumulation of fluid in the lung interstitium [12] and trigger inflammatory pathways reducing the efficiency of gas exchange in the lung [13]. It is clear that the majority of these changes are reversible [14], either by aggressive donor management through diuresis, steroids and alveolar recruitment manoeuvres in the short term or in the recipient after transplantation [15]. Unfortunately, it is clear from the increases seen in transplanted lungs with standardized and aggressive donor management algorithms that many lungs are still declined based on an initial poor gas exchange. The traditional acceptable limit of an arterial pO2 of 300 mmHg on an fiO2 of 100% and 5 cmH2O of PEEP has also been shown to be unnecessarily strict, with several studies documenting a gradual relaxation of this guideline (Fig. 1) [14,16–23]. An arterial pO2 lower than this level at the time of donor offer should prompt early assessment of the donor and optimization of haemodynamic status and ventilation, diuresis and appropriate bronchoscopic clearance of any retained secretions, rather than exclusion of the organ donor from lung donation. It is also probably no longer appropriate to consider donors with a low referral arterial pO2 as an extended criteria donor, when oxygenation improves after donor management, as it is clear that outcomes with these donors are equivalent to those with an arterial pO2 greater than 250 mmHg from the outset. Clearly, there are limits to what can be considered an acceptable arterial pO2, and the alarmingly frequent finding (>30%) of thromboembolism in the lungs of declined donors [24], and even in those accepted for transplantation [25•], remind us that as increasingly low pO2s are accepted, a greater number of donor lungs have abnormalities that may result in severe primary graft dysfunction or not recover at all. Higher risks of early dysfunction, prolonged ventilation and increased early mortality have to be weighed against waiting list mortality, with the knowledge that many causes of poor gas exchange in the donor can be reversed in the recipient if the lungs can be supported through the phase of early dysfunction. A further important limitation of the measurement of arterial pO2 is its inability to distinguish global from unilateral lung dysfunction [26]. The technique of pulmonary vein gas sampling is simple and effective at increasing donor use through identification of good single lungs for transplantation [27]. We have also found this method to predict primary graft dysfunction more reliable and advocate its routine use after donor optimization to aid decision making [28].

Figure 1

Figure 1

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Smoking

In the current era, few centres would any longer consider smoking to be an exclusion criterion for the lung donor. The traditional recommendation of excluding those with a pack year history in excess of 20 years aimed to eliminate those with chronic damage and resultant poorer graft longevity, but, clearly, current heavy smoking can have a significant detrimental effect on posttransplant outcome also. As in general thoracic surgery [29], both cumulative smoking history and current intensity have been shown to correlate with posttransplant outcome [30]. Although early gas exchange has been shown to be poorer and duration of ventilation and ICU stay prolonged, there has not been an increase in postoperative mortality with the transplantation of lungs from heavy smokers [30,31]. Importantly, intermediate-term survival and the incidence of bronchiolitis obliterans syndrome have also been comparable. We, therefore, feel that a sole finding of smoking should not be a reason to exclude a potential lung donor.

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Chest radiography

A ‘clear chest radiograph’ is an uncommon finding in the lung donor as bilateral airspace shadowing due to neurogenic pulmonary oedema and basal volume loss due to atelectasis are common consequences of brain-stem death and prolonged mechanical ventilation [32]. As these abnormalities are largely correctable by appropriate donor management, they should rarely be a cause for exclusion of a potential lung donor [33]. Up to half of those with signs of neurogenic pulmonary oedema on the initial chest radiograph can be expected to show complete resolution by the time of procurement [32], and even severe oedema has been shown to resolve after transplantation (despite severe primary graft dysfunction). The interpretation of radiographs from the lung donor remains subject to interobserver variability but has been shown to play little role in the ultimate decision whether to use the lungs for transplantation or not [34]. The role of chest radiography should, therefore, be in identifying reversible abnormalities to guide donor management and to identify unilateral abnormality, which, supplemented by pulmonary vein blood gas analysis, can be used to select suitable single lungs for transplantation.

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Bronchoscopic abnormality/Gram stain

Apart from the use of bronchoscopy as a therapeutic tool in removing retained airway secretions and allowing judicious broncho-alveolar lavage, normal bronchoscopic appearance has also traditionally formed one of the standard donor selection criteria. Evidence of aspiration of gastric contents, frank inflammation and grossly purulent secretions reaccumulating from the distal airways after suction remain exclusion criteria, but many lesser findings frequently form the basis for nonacceptance of the donor lung. These appearances are subjective and commonplace even in the donor with a normal chest radiograph and gas exchange. Subgroup analysis in small numbers of donors with purulent secretions at bronchoscopy has demonstrated an increased risk of early mortality, but the diagnosis of infection at the time of lung donor assessment remains difficult. Gram stain of tracheal secretions correlates poorly with outcome [35], and, although culture of broncho-alveolar lavage fluid remains the gold standard for diagnosis of infection in this setting [36], these results will rarely be available at the time of donor assessment. Donor infection is a common retrospective finding, and transmission to the recipient occurs in up to 8% despite appropriate antibiotic cover [37]. As expected, confirmed infection predicts prolonged ventilation and intensive care unit stay, but the presence of organisms in the donor has been shown to correlate poorly with the development of posttransplantation pneumonia in the recipient [38]. We would, therefore, consider most secretions acceptable, provided there is no reaccumulation from the distal airways following thorough bronchial toilet.

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Ischaemic time

The prolongation of allograft ischaemic time has the potential to increase activity in large procurement regions, allowing greater geographical sharing of organs and possibly enabling improved donor–recipient matching. Early International Society for Heart and Lung Transplantation (ISHLT) registry analyses and institutional reports [39] showed a distinct early survival disadvantage with ischaemic times in excess of 6 h, and a large multicentre report confirmed poorer early graft function beyond an ischaemic time of 330 min and a hazard ratio for death at 1 year of 2.70 [95% confidence interval (CI) 1.93–3.78] [20]. Most of these studies largely predated current preservation strategy. The theoretical possibility exists that current methods may increase tolerable ischaemic times. It would appear that the lung transplant community has accepted this finding as the case as the ISHLT registry data for the period 2003–2006 shows 24% of reported ischaemic times exceeding 6 h and 5% exceeding 8 h. Questions remain regarding a possible higher rate of early graft dysfunction and decreased graft longevity. A further important consideration is the finding in earlier series of an interaction between donor age and ischaemic time [40]. In current practice, longer ischaemic times in excess of 8 h will, therefore, be accepted only in the young, otherwise healthy donor.

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Donor scoring

It is, therefore, becoming clear that individual unmet standard donor criteria are rarely sufficient to prompt nonacceptance of the potential lung donor. Instead, the interaction of factors should be considered, each on a continuum from ideal to highly predictive of adverse outcome. Although we await more sensitive objective predictors of donor lung function and posttransplant outcome, good judgement and experience in donor selection remain the cornerstones of donor selection. The development of a donor scoring system to calculate a predicted risk would greatly improve decision making and allow between-centre comparison of outcomes. This development has been proven feasible on a single centre scale [41•], but wider application will require concerted collection of donor demographics and outcomes including primary graft dysfunction scores. Increasingly, the matching of the extended criteria donor to specific recipient groups will also become an issue. Each potential recipient would like to receive a perfect allograft, and the transplant centre would prefer to only use such organs, but clearly, with growing waiting lists and increasing waiting list mortality, this option is not a possibility. The use of lungs of truly marginal quality may only be justified in recipients falling out with standard recipient selection criteria. These will necessarily be high-risk transplants with generally poorer outcomes [42].

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Conclusion

At present, there are no scientific answers to many questions regarding donor acceptability in individual circumstances, and, as such, donor selection and matching with a suitable recipient remain an art. The available evidence does however support the premise that the precious resource of the cadaveric lung donor continues to be widely underutilized. Improvements in this situation will require the continued study of outcomes with the use of extended criteria lung donors in a concerted multicentre effort.

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Acknowledgement

There was no conflict of interests.

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References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

• of special interest

•• of outstanding interest

1• Snell GI, Griffiths A, Levvey BJ, Oto T. Availability of lungs for transplantation: exploring the real potential of the donor pool. J Heart Lung Transplant 2008; 27:662–667. In this article, a very high rate of donor lung utilization with no detrimental effect on outcome was shown.
2 Bhorade SM, Vigneswaran W, McCabe MA, Garrity ER. Liberalization of donor criteria may expand the donor pool without adverse consequence in lung transplantation. J Heart Lung Transplant 2000; 19:1199–1204.
3 Trulock EP, Christie JD, Edwards LB, et al. Registry of the International Society for Heart and Lung Transplantation: twenty-fourth official adult lung and heart-lung transplantation report-2007. J Heart Lung Transplant 2007; 26:782–795.
4 Fischer S, Gohrbandt B, Struckmeier P, et al. Lung transplantation with lungs from donors fifty years of age and older. J Thorac Cardiovasc Surg 2005; 129:919–925.
5•• De Perrot M, Waddell TK, Shargall Y, et al. Impact of donors aged 60 years or more on outcome after lung transplantation: results of an 11-year single-center experience. J Thorac Cardiovasc Surg 2007; 133:525–531. An extensive experience with donors between 60 and 77 years of age.
6 Christie JD, Kotloff RM, Pochettino A, et al. Clinical risk factors for primary graft failure following lung transplantation. Chest 2003; 124:1232–1241.
7 Russo MJ, Chen JM, Sorabella RA, et al. The effect of ischemic time on survival after heart transplantation varies by donor age: an analysis of the United Network for Organ Sharing database. J Thorac Cardiovasc Surg 2007; 133:554–559.
8 Oppenheimer F, Aljama P, Asensio Peinado C, et al. The impact of donor age on the results of renal transplantation. Nephrol Dial Transplant 2004; 19(Suppl 3):iii11–iii15.
9 Cuende N, Miranda B, Canon JF, et al. Donor characteristics associated with liver graft survival. Transplantation 2005; 79:1445–1452.
10 De Perrot M, Sekine Y, Fischer S, et al. Interleukin-8 release during ischemia-reperfusion correlates with early graft function in human lung transplantation. J Heart Lung Transplant 2001; 20:175–176.
11 Novick RJ, Bennett LE, Meyer DM, Hosenpud JD. Influence of graft ischemic time and donor age on survival after lung transplantation. J Heart Lung Transplant 1999; 18:425–431.
12 Novitzky D, Wicomb WN, Rose AG, et al. Pathophysiology of pulmonary edema following experimental brain death in the chacma baboon. Ann Thorac Surg 1987; 43:288–294.
13 Fisher AJ, Donnelly SC, Hirani N, et al. Enhanced pulmonary inflammation in organ donors following fatal nontraumatic brain injury. Lancet 1999; 353:1412–1413.
14 Gabbay E, Williams TJ, Griffiths AP, et al. Maximizing the utilization of donor organs offered for lung transplantation. Am J Respir Crit Care Med 1999; 160:265–271.
15 Fiser SM, Kron IL, Long SM, et al. Donor lung salvage after neurogenic pulmonary edema with the use of posttransplant extracorporeal membrane oxygenation. J Thorac Cardiovasc Surg 2001; 122:1257–1258.
16 Harjula A, Baldwin JC, Starnes VA, et al. Proper donor selection for heart-lung transplantation. The Stanford experience. J Thorac Cardiovasc Surg 1987; 94:874–880.
17 Shumway SJ, Hertz MI, Petty MG, Bolman RM 3rd. Liberalization of donor criteria in lung and heart-lung transplantation. Ann Thorac Surg 1994; 57:92–95.
18 Sundaresan S, Semenkovich J, Ochoa L, et al. Successful outcome of lung transplantation is not compromised by the use of marginal donor lungs. J Thorac Cardiovasc Surg 1995; 109:1075–1079, discussion 9–80.
19 Pilcher DV, Snell GI, Scheinkestel CD, et al. High donor age, low donor oxygenation, and high recipient inotrope requirements predict early graft dysfunction in lung transplant recipients. J Heart Lung Transplant 2005; 24:1814.
20 Thabut G, Mal H, Cerrina J, et al. Graft ischemic time and outcome of lung transplantation: a multicenter analysis. Am J Respir Crit Care Med 2005; 171:786–791.
21 Lardinois D, Banysch M, Korom S, et al. Extended donor lungs: eleven years experience in a consecutive series. Eur J Cardiothorac Surg 2005; 27:762–767.
22 Luckraz H, White P, Sharples LD, et al. Short- and long-term outcomes of using pulmonary allograft donors with low Po2. J Heart Lung Transplant 2005; 24:470–473.
23 Botha P, Fisher AJ, Dark JH. Marginal lung donors: a diminishing margin of safety? Transplantation 2006; 82:1273–1279.
24 Ware LB, Fang X, Wang Y, et al. High prevalence of pulmonary arterial thrombi in donor lungs rejected for transplantation. J Heart Lung Transplant 2005; 24:1650–1656.
25• Oto T, Excell L, Griffiths AP, et al. The implications of pulmonary embolism in a multiorgan donor for subsequent pulmonary, renal, and cardiac transplantation. J Heart Lung Transplant 2008; 27:78–85. In this article, a high rate of primary graft dysfunction in donors with pulmonary embolism reduced by use of therapeutic retrograde flush was shown.
26 McGiffin DC, Zorn JGL, Young JKR, et al. The intensive care unit oxygen challenge should not be used for donor lung function decision-making. J Heart Lung Transplant 2005; 24:1902–1905.
27 Aziz TM, El-Gamel A, Saad RA, et al. Pulmonary vein gas analysis for assessing donor lung function. Ann Thorac Surg 2002; 73:1599–1604, discussion 604–5.
28 Botha P, Trivedi D, Searl CP, et al. Differential pulmonary vein gases predict primary graft dysfunction. Ann Thorac Surg 2006; 82:1998–2002.
29 Nakagawa M, Tanaka H, Tsukuma H, Kishi Y. Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery. Chest 2001; 120:705–710.
30 Oto T, Griffiths AP, Levvey B, et al. A donor history of smoking affects early but not late outcome in lung transplantation. Transplantation 2004; 78:599–606.
31 Botha P, Trivedi D, Weir CJ, et al. Extended donor criteria in lung transplantation: impact on organ allocation. J Thorac Cardiovasc Surg 2006; 131:1154–1160.
32 McCowin MJ, Hall TS, Babcock WD, et al. Changes in radiographic abnormalities in organ donors: associations with lung transplantation. J Heart Lung Transplant 2005; 24:323–330.
33 Straznicka M, Follette DM, Eisner MD, et al. Aggressive management of lung donors classified as unacceptable: excellent recipient survival one year after transplantation. J Thorac Cardiovasc Surg 2002; 124:250–258.
34 Bolton JS, Padia SA, Borja MC, et al. The predictive value and inter-observer variability of donor chest radiograph interpretation in lung transplantation. Eur J Cardiothorac Surg 2003; 23:484–487.
35 Weill D, Dey GC, Hicks RA, et al. A positive donor gram stain does not predict outcome following lung transplantation. J Heart Lung Transplant 2002; 21:555–558.
36 Avlonitis VS, Krause A, Luzzi L, et al. Bacterial colonization of the donor lower airways is a predictor of poor outcome in lung transplantation. Eur J Cardiothorac Surg 2003; 24:601–607.
37 Ruiz I, Gavalda J, Monforte V, et al. Donor-to-host transmission of bacterial and fungal infections in lung transplantation. Am J Transplant 2006; 6:178–182.
38 Bonde PN, Patel ND, Borja MC, et al. Impact of donor lung organisms on postlung transplant pneumonia. J Heart Lung Transplant 2006; 25:99–105.
39 Snell GI, Rabinov M, Griffiths A, et al. Pulmonary allograft ischemic time: an important predictor of survival after lung transplantation. J Heart Lung Transplant 1996; 15:160–168.
40 Meyer DM, Bennett LE, Novick RJ, Hosenpud JD. Effect of donor age and ischemic time on intermediate survival and morbidity after lung transplantation. Chest 2000; 118:1255–1262.
41• Oto T, Levvey BJ, Whitford H, et al. Feasibility and utility of a lung donor score: correlation with early posttransplant outcomes. Ann Thorac Surg 2007; 83:257–263. The above article demonstrates feasibility of lung donor score to predict posttransplant outcome.
42 Pierre AF, Sekine Y, Hutcheon MA, et al. Marginal donor lungs: a reassessment. J Thorac Cardiovasc Surg 2002; 123:421–427.
Keywords:

donor selection; lung transplantation; organ donors

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