Preventable Death: Children on the Transplant Waiting List

Transcription

1 American Journal of Transplantation 28; 8: Wiley Periodicals Inc. Special Article C 28 The Authors Journal compilation C 28 The American Society of Transplantation and the American Society of Transplant Surgeons doi: /j x Preventable Death: Children on the Transplant Waiting List S. V. McDiarmid a,,w.s.cherikh b and S. C. Sweet c a Professor of Pediatrics and Surgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA b Senior Biostatistician, UNOS Research Department, Richmond, VA c Associate Professor of Pediatrics, Washington University, St Louis, MO Corresponding author: Sue V. McDiarmid, smcdiarmid@mednet.ucla.edu Children, especially those under 5 years of age, have the highest death rate on the transplant waiting list compared to any other age range. This article discusses the concept, supported by OPTN data, that there is an age range of small pediatric donors, which are almost exclusively transplanted into small pediatric transplant candidates. Allocation policies that allow broader sharing of small pediatric donors into small pediatric candidates are likely to decrease death rates of children on the waiting list. As well, although the number of pediatric deceased donors continues to decline, improving consent rates for eligible pediatric donors, and judicious use of pediatric donors after cardiac death, can enhance the pediatric deceased donor supply. Key words: Allocation, death risk, deceased donor organs, pediatric transplantation Recieved 27 June 28, revised 4 August 28 and accepted for publication 22 August 28 Medicine has always tried to prevent the death of those affected by disease. The impetus to honor this ideal is particularly compelling in children, who do not suffer from the inevitable degenerative diseases of adulthood. Sadly, we fail to prevent the deaths of the children who are among the 17 patients dying each day in the United States awaiting transplantation. These children present us with unique opportunities for intervention that could minimize these deaths without, most importantly, impacting the access of adults to transplantation. Can we better utilize the pediatric donors we have? Are we able to uncover an untapped source of pediatric donors? Can we devise innovative allocation policies, capitalizing on the obvious distinguishing characteristic of children, their size, to distribute small donor organs, irrespective of current geographic distribution boundaries, to the children in greatest need? This article will focus on four major themes: the youngest children on the transplant waiting list have the highest rate of death; for pediatric donors, there is a cut off in age that characterizes those pediatric donors that can only be placed into small children; the distribution of these organs should not be constrained by geography and the pediatric donor potential has yet to be realized. The need for transplantation, regardless of age, can be appreciated by a snap shot of the OPTN (Organ Procurement Transplant Network) transplant waiting list on any given day. For example, on April 25, 28, 1935 children and adults awaited solid organ transplantation; however, for the entire year of 27, 1588 children and 2 46 adults were transplanted. This discrepancy between supply and demand has lead to increasing numbers of patients dying on the waiting list (1). According to OPTN data, in the last 5 years 138 children died on the list compared to adults. While the absolute number of children who died in comparison to adults appears small, the rate of death, that is deaths adjusted by time waiting, provides a different and compelling view. OPTN data (Figure 1) show that across all age ranges and organ types, children less than 5 years of age, (and up to 1 years of age for liverintestinal candidates) have a much higher death rate compared to any other age group, including adults more than 65 years of age. Infants, those less than 1 year of age, are especially vulnerable to dying before transplantation. However, this risk is not evenly distributed across the country. There are substantial regional differences for death rates on the waiting list, regardless of age between the eleven regions. For the most vulnerable children, those aged 5 years, OPTN data show these differences in Figure 2. As well, geographic disparity in death rates has also been reported within a region (2). Some of this difference could be explained by regional differences in the willingness of centers to accept an organ after it has gone out to be shared on the national list. An analysis of the OPTN database showed that across regions, for all pediatric transplants the median percent of transplanted national share organs was 31% (lowest, 15%, in Region 5, highest, 44%, in Region 2). Interestingly, Region 2 tended to have lower death rates for children as compared to some other regions. This observation deserves further analysis. Another explanation of regional 2491

2 McDiarmid et al. Rates 2,5 2, 1,5 1, 5 < Heart/Heart- Lung Lung Liver Liver-Intestine Kidney Figure 1: Waiting list death rates (including removal for too sick to transplant) during by organ type and age at listing. From the OPTN database. differences in death rates could be the willingness of centers within a region to exploit different organ types. This is most relevant for pediatric liver transplantation. As can be seen in Figure 3, there are some regional differences in the use of whole deceased donors, living donors, and technical variant deceased donors. The numbers however are quite small within each region for anything other than whole deceased donors and the variation is most likely center specific rather that region specific. The ideal donor for small children awaiting liver, heart, lung or liver intestinal transplantation, is a similar sized donor. For kidney donors and recipients, as will be discussed below, the age/size match between donor and recipient is not so clear cut. Examining the age ranges of recipients for age ranges of pediatric donors, it is possible to determine a pediatric donor age range that is virtually unusable in adults. Figure 4, from OPTN database analyses, shows the age ranges of recipients of pediatric donors according to organ type. Two facts are immediately obvious. First, the majority of pediatric donors <18 years of age are allocated to adults, Second, virtually no pediatric heart, lung, liver Rates 3, 2,5 2, 1,5 1, 5 Heart/Heart-Lung Lung Liver Liver-Intestine Kidney Region Note: There were no candidates waiting for lung in Regions 6, 7 and 9. Figure 2: Waiting list death rates (including removal for too sick to transplant) during by OPTN regions and organ type for candidates aged 5 at listing. From the OPTN database. Whole Deceased Donor Technical Variant Deceased Donor Living Donor 1% 9% 8% 7% 6% 5% 4% 3% 2% 1% % Region Figure 3: The number of pediatric liver transplants during by region and procedure type. From the OPTN database. or intestine donors less than 6 years of age are allocated into adults or even teens. Even for donors less than 11 years of age, very few are transplanted into adults. In contrast, the majority of pediatric donors aged years are placed into adults providing an important source of organs that should rightfully be directed to adults in urgent need for transplantation. An excellent example of this need is the 7.6 death rate per patient year at risk for adults listed for acute liver failure, as compared to a 4.1 death rate for children listed with acute liver failure (3). Given the evidence that there are subsets of pediatric liver, heart, lung and intestine donors that are uniquely suited to small pediatric recipients, we could develop innovative allocation policies for these small pediatric donors that would distribute these organs efficiently over broad geographic ranges to small children with the greatest medical urgency for transplantation. The concept of broader sharing of organs for patients in most need has already been tested in some regions and shown to decrease death on the waiting list (4). It is therefore becoming more difficult to justify our current practice of organ offers that first exhaust the local, then regional, and finally national lists. The geographic boundaries that define local donor service areas and the regions were administrative constructs that were never intended to create similar populations bases for either donors or recipients. Thinking beyond these artificial constraints that govern allocation, one could envision for small pediatric donors a distribution area for which the only logical boundary would not be distance from the donor hospital but time, specifically estimated cold ischemia time. Experience has already taught transplant surgeons the ranges of acceptable cold ischemia times that protect graft function. Whereas there are certain instances in which cold ischemia time should be minimized, for example for the so called extended criteria donor (5), these conditions rarely apply to pediatric organs which are often considered the best quality donors. In any allocation sequence that prioritizes national sharing of selected organs to subgroups of candidates waiting, the judgment of acceptable cold ischemia American Journal of Transplantation 28; 8:

3 Pediatric Death on Waiting List Recipients -1 Recipients Recipients 18+ Recipients -11 Recipients Recipients A Heart 7 6 B Lung Recipients -11 Recipients Recipients 18+ C Liver Recipients -5 Recipients 6-1 Recipients Recipients 18+ D Kidney Figure 4: Distribution of deceased donor transplants, by organ type from pediatric donors during 26 27, by recipient and donor age groups. Figure 3A: Heart transplants; Figure 3B; Lung transplants; Figure 3C Liver transplants; Figure 4D kidney transplants. time should be made at the discretion of the accepting transplant surgeon and not subject to rigid rule making. If changes in allocation are made that would direct small pediatric donors to the sickest size matched pediatric candidate, the impact on adolescents and adults waiting should be considered. An OPTN data analysis examined the percent of donors <12 years of age transplanted into adults and adolescents by organ type. Very few adult kidney, liver, heart or lung adults recipients (5%, 1%,.5%,.4% respectively) received a donor <12 years of age. Relatively more adolescent kidney, liver, heart, and lung recipients (8%, 21%, 12%, and 27% respectively) received a <12 year old donor. Although in current allocation policies adolescents already receive some priority over adult recipients, the larger of the small pediatric donors might be also suitable for the adolescent. Adolescents in general have a lower death rate on the list than younger children, so that their death rate on the list is unlikely to be affected by the proposal to direct small organs to small recipients. However, any proposed changes in allocation policy should be carefully assessed for the effect on all potential recipients. There is already evidence that currently we do not efficiently distribute pediatric donor organs. An OPTN database analysis showed that young children can die on the list without ever receiving a donor offer, or have had donor offers that were turned down by their center but later accepted elsewhere. For example, on the waiting list between 1/1/5 and 6/3/6, of children aged between and 5 years awaiting liver, lung or heart transplantation 138 died (or were removed for too sick to transplant) with the refusal of at least one offer, and 159 never received an offer. The two most common reasons for such turndowns were operational center issues or donor size. This suggests that some pediatric centers are not always staffed to be able to transplant around the clock, and that a more efficient system to quickly and widely distribute small donors to the sickest small children is needed. Many pediatric transplant physicians and surgeons, including this author, have either made or received personal phone calls from colleagues trying to place a perfectly usable small sized pediatric organ, despite the best efforts of the UNOS Organ Center, and dedicated OPO coordinators making multiple phone calls required to stay true to the match run. American Journal of Transplantation 28; 8:

4 McDiarmid et al. In adopting a general philosophy that proritizes small donors allocated to small recipients at greatest risk of death, special needs of subsets of the pediatric waiting list population deserve attention. This particularly applies to children with end stage kidney disease awaiting kidney transplantation. In general, pediatric kidney transplant candidates are older than other pediatric candidates on the waiting list, and while the lower chance of dying on the list is low compared to other pediatric candidates, the small kidney candidates are still at highest risk while waiting (6). As well, single kidneys from small pediatric kidney donors have a substantial risk of poor graft function (7). Currently, children less than 18 years of age in need of kidney transplantation already have priority for donors less than 35 years of age over almost all other candidates. Pediatric kidney candidate death on the waiting list may be driven by different factors compared to other children awaiting organs, demonstrated by the observation that 48.9% of pediatric kidney candidates dying on the OPTN waiting list during were listed as inactive at the time of death. The pediatric nephrology community is examining several important initiatives to minimize death on the kidney waiting list to prioritize those children with the highest medical urgency, including those losing dialysis access, those with unusually long waiting times, and highly sensitized children. Broader sharing for these most medically urgent pediatric kidney candidates may be an important consideration as the proposal for a new national kidney allocation system, currently under development, is finalized. What is the potential to increase the number of pediatric donors (< 18 years)? The benefits are obvious. More small pediatric donors, with the possible exception of the small kidney donors, would provide more life saving organs for small pediatric recipients. As well, organs from adolescent donors are very often are considered excellent quality organs, not only for adolescents, but for critically ill adults. In the special circumstance of adolescents liver donors, these are often ideal for the technique of split liver transplantation, (which creates two transplantable liver segments) (8,9). However, the number of pediatric donors per year has not increased. In fact, there has been some decline over the past 1 years (Figure 5) in pediatric donor numbers (1). While this might be due in part to fewer accidental deaths and advances in pediatric critical care medicine, there is increasing evidence that there are eligible pediatric donors for whom consent is never obtained. The conversion rate, that is the percent of brain dead children eligible for donation for which consent is obtained, is not well understood. Currently, very little data exist to compute the conversion rate for children, as mandatory reporting of eligible deaths did not require age to be recorded until quite recently. In an OPTN data analysis of eligible deaths reported from Children s Hospitals in the United States, where all eligible donors were children, the conversion rate was at the extremes of variability ranging from to 1%. As well, despite the remarkable success of the Human Resources and Service Administration (HRSA) lead collaborative for 1,25 1,125 1, Figure 5: The number of pediatric decease donors from 1995 to 27 by donor age group. organ donation initiated in 23, which has increased the number of organ available for transplantation by 24% (11), there has not been a parallel increase in the number of pediatric donors (12). In a survey of all 58 OPO s in the United States, the consent rate for eligible pediatric donors varied from 48 79% between regions, and was lowest in children age 11 years particularly if they where located in a community hospital without a pediatric intensive care unit (13). As well, some advocates of pediatric donation within the pediatric critical care community, report a wide range of variation in the attitudes and practice of pediatric intensivists in regard to organ donation. Advocates of pediatric donation stress the importance of honoring the wishes of the family to donate their child s organs, and that this act allows a sense of redemption for their child s life. The same principle of enabling a willing family to donate is relevant to increasing pediatric donation after cardiac death. Although the reported number of DCD pediatric donors and recipients is still small, there is evidence that the graft survival of pediatric DCD organs is comparable to liver and kidney brain donors (14). It is reasonable to conclude that far from being tapped out, there is good evidence that improving pediatric donor identification, management and consent rates (including DCDs) could substantially improve the pediatric donor supply. With a mandate to minimize death on the pediatric transplant waiting list, a Summit for Pediatric Donation and Transplantation was convened March, 27, in San Antonio, Texas. The goal was to bring all three essential constituents the pediatric critical care, OPO, and transplant physician communities to the discussion table. The critical care and OPO participants developed an agenda for changes and improvements in practice including: more consistent definitions of pediatric brain death, improved pediatric donor management including the role of hormonal therapy, ways to decrease the number of organs lost because of coroner and medical examiner intervention (15), reach out efforts to reluctant colleagues to participate in improving pediatric organ donation rates (,17), improved communications between the local OPOs and their 2494 American Journal of Transplantation 28; 8:

5 Pediatric Death on Waiting List pediatric critical care collegues, and best practices to obtain consent in the unique circumstance of death to a child (18). A Town Hall Meeting combining the perspectives of all conference participants, including donor families, addressed the special circumstances of pediatric organ donation after cardiac death. The pediatric transplant physicians and surgeons reviewed extensive, organ specific data pertinent to why children die on the waiting list and began to formulate new allocation policies that would minimize pediatric deaths, but not at the expense of adults. Two common themes emerged: better utilization of available organs and broader sharing of small pediatric donors. Specific targets for improving donor utilization were the use of en-bloc kidneys from small pediatric donors (19,2), and pushing the envelope to use heart and lung donors beyond the conventional parameters currently in use. The heart, lung, liver and intestine working groups all suggested changes in allocation policy that would allow small pediatric (potentially those less than 11 years of age) to be first shared beyond the local area either regionally or into Zone A and B patients for heart and lung donors, with early national sharing for the sickest pediatric patients waiting. As well, it was recognized that living donors, despite concerns about donor safety, are still an important source of organs to fill the short-fall in deceased donors for children. This Pediatric Summit marked the first step in bringing together the participants whose collaboration is essential if we are to substantially reduce the loss of children s lives on the transplant waiting list. As a result substantial progress has already been made. Changes in allocation policies recommending broader sharing of pediatric heart, lung liver and intestine donors <11 years of age for the sickest candidates on the list have been formalized by the OPTN/UNOS Pediatric Committee circulated for Public Comment and were passed by the OPTN/UNOS Board at its June 28 meeting. The death of any child brings a distinctive pathos to human tragedy. The cumulative hope of young lives thwarted, and their futures denied not only to their own family, but to our society, may provide just the impetus needed to attempt to solve this specific and preventable loss of child life years. In so doing, we may find the will, and the methods, to decrease the even larger number of adults dying on transplant waiting lists in this country. Acknowledgment This work was supported wholly or in part by Health Resources and Services Administration contract C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. References 1. Pomfret EA, Sung RS, Allan J et al. Solving the organ shortage crisis: The 7th Annual American Society of Transplant Surgeons State-of-the-Art Winter Symposium. Am J Transplant 28; 8: Barshes NR, Becker NS, Washburn WK et al. Geographic disparities in deceased donor liver transplantation within a single UNOS region. Liver Transpl 27; 13: McDiarmid SV, Goodrich NP, Harper AM et al. Liver transplantation for status 1: The consequences of good intentions. Liver Transpl 27; 13: Humar A, Khwaja K, Glessing B et al. Regionwide sharing for status 1 liver patients beneficial impact on waiting time and pre- and posttransplant survival. Liver Transpl 24; 1: Cameron AM, Ghobrial RM, Yersiz H et al. 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