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Is there a future for transplantation as we know it today?
Is There a Future for Transplantation as We Know It Today? H. Ga¨bel
T
ITLES with a question mark are intriguing. The question may well be rhetorical, the answer may be both yes and no, or the author may try to answer the question or leave the question open. I will answer the question from the starting point in transplantation as we know it today, ie, the current practices resulting from 40 to 50 years of experience gained in the world of transplantation. Judging from current trends, I will try to predict where transplantation is heading in some respects. It has been said that transplantation is the victim of its own success. The good results obtained have led to widening indications and acceptance of patients, for transplantation resulting in an increased demand for the procedure. Waiting lists are growing all over the world. Critics have claimed that the waiting lists have been made up to show a great demand for transplantation. This is not true, but, because many more patients are listed than will ever have the chance to get a transplant, false hopes have been created in candidates. The limited current availability of cadaver organs warranted some adjustment to realities. Waiting lists will continue to grow. The number of suitable recipients will increase because high-risk patients are now accepted. In addition, there are novel indications for transplantation. Moreover, the demand for retransplantations will grow as grafts fail after many years of function. The first- and second-generation transplantologists who have shaped transplantation as we know it today will not be here. These great pioneers were much involved in the discussions on ethical issues leading to the current practices. Many of the pioneers of transplantation have given their personal accounts in The History of Transplantation: Thirty-Five Recollections.1 The current and future generations of transplantologists may not be as prepared as the pioneers to sacrifice their private lives for the benefit of transplantation. I was recently informed about the difficulties to find trained surgeons in one major center prepared to simultaneously transplant all organs retrieved from a multiorgan donor. In spite of the fact that most deceased donors yield multiple organs and expanded or suboptimal donors are increasingly being used, there is a growing gap between the supply and the demand for organs suitable for transplantation. Compilations of the relative number of cadaveric donors
in various countries or procurement areas show that the number varies between more than 30 per million population (pmp) and less than 10 pmp.2 The number of potential organ donors may vary between countries depending on characteristics such as the age-mix, the average life expectancy of the population, the mortality pattern, the number of road traffic accidents, as well as the level of general hospital and intensive care. A major part of the difference between the successful and less successful procurement programs as far as actual donors are concerned is accounted for by organization. The Spanish model3 has been successful not only in Spain, but also in Portugal and in Italy. The shortage of heart-beating cadaveric donors has resulted in a continuous reevaluation of relative contraindications to organ donation. There are now few, if any, ideal donors; more and more are nonideal or suboptimal donors. How far can we go without risking deteriorating results? In the end the recipients pay. There is a delicate balance between accepting an organ, which is not good enough, and discarding a graft with life-sustaining properties. In the future, we will have to accept fewer cadaveric donors. Early diagnosis and prognosis of subarachnoid hemorrhages and cerebrovascular accidents will have consequences for procurement. Early surgical interventions yield good results. Patients who in the past died under circumstances making heart-beating organ donation an option not only recover now, but also enjoy a good quality of life.4 If, on the other hand, the prognosis quad vitam is considered hopeless, treatment may be withheld as being not in the best interests of the patient, and heart-beating organ donation may be out of the question. But, is it possible that sometimes the prognosis quad vitam is not correct? Has the time come to reconsider elective ventilation, Nontherapeutic ventilation for patients with a bad prognosis to make donation possible.5,6 Maybe it is time to reclaim the discarded opportunity of non– heart-beating donation. There is no difference in the long-term outcome between kidneys from donors with and without a heartbeat.7 Using current methods not only From the National Board of Health and Welfare, Stockholm, Sweden. Address reprint requests to Dr H. Ga¨bel, National Board of Health and Welfare, 10630 Stockholm, Sweden. E-mail: [email protected]
© 2003 by Elsevier Science Inc. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/03/$–see front matter doi:10.1016/S0041-1345(03)00205-7
Transplantation Proceedings, 35, 1245–1247 (2003)
1245
GA¨ BEL
1246
kidneys but also livers and lungs8 can be procured from non– heart-beating donors. Will the consent to cadaver organ donation be reconsidered? It has been argued that presumed consent is the “solution to the critical donor shortage,”9,10 but is there something beyond presumed consent? “Would our society accept some sort of statutory ownership of those organs (from a dead donor) being transferred from the family to some social agency, such as the city, town, county or state? That might be achievable, but would seem to be difficult. But on death, the custody of those organs should be considered as being transferred to the local organ bank automatically.”11 How presumed is presumed consent? Not at all.12 Be it informed consent or presumed consent, the families may decide on donation if they are informed about this option. The refusal rate varies greatly between procurement regions. In Spain, the gold standard when it comes to donation, it varies between 10% and 40%3 and, in the United States,13 consent rates are higher when the physician in charge is assisted by a professional who has expert knowledge and skills in how to communicate with grieving relatives. When it comes to general hospital staff, we should assume nothing about their attitudes and skills in communicating with grieving relatives. In an ideal world, all health care professionals would have the necessary skills to effectively communicate with relatives in crises, but for the time being it would be advantageous if the task could be handled by professionals, not solely to maximize donation but also to help relatives cope with the crisis after a sudden and unexpected death. Relatives who have consented to donation feel better and are more satisfied with their decision to donate than those who have not accepted donation.13 Would money help? Financial incentives for cadaver organ donation have been refuted for many years. “Until now organ donation has relied on the voluntarism and altruism of uncompensated living donors and of uncompensated family members of cadaver donors.”14 “The Pennsylvania law permitted a pilot in 1994 which was implemented in January 2002;” it is being promoted quietly only for living donors. Almost no one has used the fund this year for cadaver donation (for food and lodging) for donor families (Nathan H., personal communication, 2002). The use of “financial incentives” is a way to remove financial disincentives. Because living donors are increasingly being used, it is unreasonable that, apart from the pain and discomfort of the operation, they also have to suffer economic losses because of expenses incurred and income lost in connection with the donor operation. It is reasonable that living donors are reimbursed for their expenses, neither more nor less, a gesture that seems increasingly important as the living donor pool expands. The first successful kidney transplantations used closely related (siblings and parents) living donors, leading many transplantation programs to start with the use of living donors. Gradually more and more organs from cadaveric
donors were used, but, because of the failure of these organs to meet the demand, living donors are now gaining prominance. Moving from closely to more distantly genetically and emotionally related donors (husbands and wives), unknown altruistic donors are now also accepted.15 Also, paid organ donors do exist. We know from reports from Israel16 that paid living kidney donors are being used. It is also claimed that the transplants are generally successful and that the medical care seems to meet international standards. The transactions now have received semiofficial recognition from the Israeli Ministry. The practice seems to open up paid living organ donation for more general acceptance as advocated by the forum for transplantation ethics.17,18 The outcome for the recipients has been reported to be good, but one also has to consider the outcome for the donors.19,20 SUMMARY AND CONCLUSIONS
If I have to answer the question in the title, the answer will be yes and no. No, there is no future for transplantation, as we know it today. The practices and policies are constantly changing. I hope that in the near future the number of cadaveric donors will increase in most countries owing to improvements in procurement organizations and better medical management of donors. I doubt, however, that it is possible to attain the number of cadaveric donors realized in Spain. Some of us may live to see that the cadaveric donor pool has decreased. Maximized donation without financial incentives for donors or their surviving families will go a long way to meet the demand, but I fear that in the future there will be some financial incentives involved in donation. Yes, there is a future for transplantation and there always will be, but not for transplantation as we know it today The question is whether xenotransplantation or stem cell therapy will be there to take over as the number of allotransplants fail to meet the increasing demand for organ allografts, a demand that cannot be met by a judicious combination of organs from living and deceased donors. REFERENCES 1. Terasaki P (ed): History of Transplantation: Thirty-Five Recollections. Los Angeles: UCLA Tissue Typing Laboratory; 1991 2. Baxter D: Beyond Comparison: Canada’s Organ Donation Rates in an International Context. The Urban Futures Institute Report 51. www.urbanfutures.com 3. Matesantz R, Miranda B: Organ Donation for Transplantation—the Spanish Model. Madrid, Spain: Grupo Aula Medica; 1996 4. Elf K, Nilsson P, Enblad P: Neurol Crit Care 30:2129, 2002 5. Feest TG, Rias HN, Collins CH, et al: Lancet 335:1133, 1990 6. Br Med J 310:714, 1995 7. Weber M, Dindo D, Demartines N, et al: N Engl J Med 347:248, 2002 8. Steen S, Sjo ¨berg T, Pierre L: Lancet 357:825, 2001 9. Kennedy I, Sells RA, Daar AS, et al: Lancet 341:1650, 1998 10. Futterman L: Am J Crit Care 4:383, 1995
FUTURE FOR TRANSPLANTATION? 11. Moore FD: Transplant Proc 20(suppl 1):1061, 1998 12. Ga¨bel H: Transplant Proc 28:27, 1996 13. Beasley CL: Transplant Rev 13:31, 1999 14. Delmonico FL, Arnold R, Scheper-Hughes N, et al: N Engl J Med 346:2002, 2002 15. Lewinsky NG: N Engl J Med 2000 343:430, 2000
1247 16. Freidlaender M: Lancet 359:971, 2002 17. Radcliffe-Richards RJ, Daar AS, Gutman RD, et al: Lancet 351:1950, 1998 18. Daar AS: J Med Ethics 24:365, 1998 19. Zargooshi J, Barry JM, Gritsch A: J Urol 165:386, 2001 20. Zargooshi J: J Urol 166:1790, 2001
T
ITLES with a question mark are intriguing. The question may well be rhetorical, the answer may be both yes and no, or the author may try to answer the question or leave the question open. I will answer the question from the starting point in transplantation as we know it today, ie, the current practices resulting from 40 to 50 years of experience gained in the world of transplantation. Judging from current trends, I will try to predict where transplantation is heading in some respects. It has been said that transplantation is the victim of its own success. The good results obtained have led to widening indications and acceptance of patients, for transplantation resulting in an increased demand for the procedure. Waiting lists are growing all over the world. Critics have claimed that the waiting lists have been made up to show a great demand for transplantation. This is not true, but, because many more patients are listed than will ever have the chance to get a transplant, false hopes have been created in candidates. The limited current availability of cadaver organs warranted some adjustment to realities. Waiting lists will continue to grow. The number of suitable recipients will increase because high-risk patients are now accepted. In addition, there are novel indications for transplantation. Moreover, the demand for retransplantations will grow as grafts fail after many years of function. The first- and second-generation transplantologists who have shaped transplantation as we know it today will not be here. These great pioneers were much involved in the discussions on ethical issues leading to the current practices. Many of the pioneers of transplantation have given their personal accounts in The History of Transplantation: Thirty-Five Recollections.1 The current and future generations of transplantologists may not be as prepared as the pioneers to sacrifice their private lives for the benefit of transplantation. I was recently informed about the difficulties to find trained surgeons in one major center prepared to simultaneously transplant all organs retrieved from a multiorgan donor. In spite of the fact that most deceased donors yield multiple organs and expanded or suboptimal donors are increasingly being used, there is a growing gap between the supply and the demand for organs suitable for transplantation. Compilations of the relative number of cadaveric donors
in various countries or procurement areas show that the number varies between more than 30 per million population (pmp) and less than 10 pmp.2 The number of potential organ donors may vary between countries depending on characteristics such as the age-mix, the average life expectancy of the population, the mortality pattern, the number of road traffic accidents, as well as the level of general hospital and intensive care. A major part of the difference between the successful and less successful procurement programs as far as actual donors are concerned is accounted for by organization. The Spanish model3 has been successful not only in Spain, but also in Portugal and in Italy. The shortage of heart-beating cadaveric donors has resulted in a continuous reevaluation of relative contraindications to organ donation. There are now few, if any, ideal donors; more and more are nonideal or suboptimal donors. How far can we go without risking deteriorating results? In the end the recipients pay. There is a delicate balance between accepting an organ, which is not good enough, and discarding a graft with life-sustaining properties. In the future, we will have to accept fewer cadaveric donors. Early diagnosis and prognosis of subarachnoid hemorrhages and cerebrovascular accidents will have consequences for procurement. Early surgical interventions yield good results. Patients who in the past died under circumstances making heart-beating organ donation an option not only recover now, but also enjoy a good quality of life.4 If, on the other hand, the prognosis quad vitam is considered hopeless, treatment may be withheld as being not in the best interests of the patient, and heart-beating organ donation may be out of the question. But, is it possible that sometimes the prognosis quad vitam is not correct? Has the time come to reconsider elective ventilation, Nontherapeutic ventilation for patients with a bad prognosis to make donation possible.5,6 Maybe it is time to reclaim the discarded opportunity of non– heart-beating donation. There is no difference in the long-term outcome between kidneys from donors with and without a heartbeat.7 Using current methods not only From the National Board of Health and Welfare, Stockholm, Sweden. Address reprint requests to Dr H. Ga¨bel, National Board of Health and Welfare, 10630 Stockholm, Sweden. E-mail: [email protected]
© 2003 by Elsevier Science Inc. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/03/$–see front matter doi:10.1016/S0041-1345(03)00205-7
Transplantation Proceedings, 35, 1245–1247 (2003)
1245
GA¨ BEL
1246
kidneys but also livers and lungs8 can be procured from non– heart-beating donors. Will the consent to cadaver organ donation be reconsidered? It has been argued that presumed consent is the “solution to the critical donor shortage,”9,10 but is there something beyond presumed consent? “Would our society accept some sort of statutory ownership of those organs (from a dead donor) being transferred from the family to some social agency, such as the city, town, county or state? That might be achievable, but would seem to be difficult. But on death, the custody of those organs should be considered as being transferred to the local organ bank automatically.”11 How presumed is presumed consent? Not at all.12 Be it informed consent or presumed consent, the families may decide on donation if they are informed about this option. The refusal rate varies greatly between procurement regions. In Spain, the gold standard when it comes to donation, it varies between 10% and 40%3 and, in the United States,13 consent rates are higher when the physician in charge is assisted by a professional who has expert knowledge and skills in how to communicate with grieving relatives. When it comes to general hospital staff, we should assume nothing about their attitudes and skills in communicating with grieving relatives. In an ideal world, all health care professionals would have the necessary skills to effectively communicate with relatives in crises, but for the time being it would be advantageous if the task could be handled by professionals, not solely to maximize donation but also to help relatives cope with the crisis after a sudden and unexpected death. Relatives who have consented to donation feel better and are more satisfied with their decision to donate than those who have not accepted donation.13 Would money help? Financial incentives for cadaver organ donation have been refuted for many years. “Until now organ donation has relied on the voluntarism and altruism of uncompensated living donors and of uncompensated family members of cadaver donors.”14 “The Pennsylvania law permitted a pilot in 1994 which was implemented in January 2002;” it is being promoted quietly only for living donors. Almost no one has used the fund this year for cadaver donation (for food and lodging) for donor families (Nathan H., personal communication, 2002). The use of “financial incentives” is a way to remove financial disincentives. Because living donors are increasingly being used, it is unreasonable that, apart from the pain and discomfort of the operation, they also have to suffer economic losses because of expenses incurred and income lost in connection with the donor operation. It is reasonable that living donors are reimbursed for their expenses, neither more nor less, a gesture that seems increasingly important as the living donor pool expands. The first successful kidney transplantations used closely related (siblings and parents) living donors, leading many transplantation programs to start with the use of living donors. Gradually more and more organs from cadaveric
donors were used, but, because of the failure of these organs to meet the demand, living donors are now gaining prominance. Moving from closely to more distantly genetically and emotionally related donors (husbands and wives), unknown altruistic donors are now also accepted.15 Also, paid organ donors do exist. We know from reports from Israel16 that paid living kidney donors are being used. It is also claimed that the transplants are generally successful and that the medical care seems to meet international standards. The transactions now have received semiofficial recognition from the Israeli Ministry. The practice seems to open up paid living organ donation for more general acceptance as advocated by the forum for transplantation ethics.17,18 The outcome for the recipients has been reported to be good, but one also has to consider the outcome for the donors.19,20 SUMMARY AND CONCLUSIONS
If I have to answer the question in the title, the answer will be yes and no. No, there is no future for transplantation, as we know it today. The practices and policies are constantly changing. I hope that in the near future the number of cadaveric donors will increase in most countries owing to improvements in procurement organizations and better medical management of donors. I doubt, however, that it is possible to attain the number of cadaveric donors realized in Spain. Some of us may live to see that the cadaveric donor pool has decreased. Maximized donation without financial incentives for donors or their surviving families will go a long way to meet the demand, but I fear that in the future there will be some financial incentives involved in donation. Yes, there is a future for transplantation and there always will be, but not for transplantation as we know it today The question is whether xenotransplantation or stem cell therapy will be there to take over as the number of allotransplants fail to meet the increasing demand for organ allografts, a demand that cannot be met by a judicious combination of organs from living and deceased donors. REFERENCES 1. Terasaki P (ed): History of Transplantation: Thirty-Five Recollections. Los Angeles: UCLA Tissue Typing Laboratory; 1991 2. Baxter D: Beyond Comparison: Canada’s Organ Donation Rates in an International Context. The Urban Futures Institute Report 51. www.urbanfutures.com 3. Matesantz R, Miranda B: Organ Donation for Transplantation—the Spanish Model. Madrid, Spain: Grupo Aula Medica; 1996 4. Elf K, Nilsson P, Enblad P: Neurol Crit Care 30:2129, 2002 5. Feest TG, Rias HN, Collins CH, et al: Lancet 335:1133, 1990 6. Br Med J 310:714, 1995 7. Weber M, Dindo D, Demartines N, et al: N Engl J Med 347:248, 2002 8. Steen S, Sjo ¨berg T, Pierre L: Lancet 357:825, 2001 9. Kennedy I, Sells RA, Daar AS, et al: Lancet 341:1650, 1998 10. Futterman L: Am J Crit Care 4:383, 1995
FUTURE FOR TRANSPLANTATION? 11. Moore FD: Transplant Proc 20(suppl 1):1061, 1998 12. Ga¨bel H: Transplant Proc 28:27, 1996 13. Beasley CL: Transplant Rev 13:31, 1999 14. Delmonico FL, Arnold R, Scheper-Hughes N, et al: N Engl J Med 346:2002, 2002 15. Lewinsky NG: N Engl J Med 2000 343:430, 2000
1247 16. Freidlaender M: Lancet 359:971, 2002 17. Radcliffe-Richards RJ, Daar AS, Gutman RD, et al: Lancet 351:1950, 1998 18. Daar AS: J Med Ethics 24:365, 1998 19. Zargooshi J, Barry JM, Gritsch A: J Urol 165:386, 2001 20. Zargooshi J: J Urol 166:1790, 2001