TRANSPLANT INNOVATION: WHAT HAVE WE LEARNED? ..

DENTON A. COOLEY, MD JOHN J. FUNG, MD, PhD JAMES B. YOUNG, MD Texas Institute Cleveland Clinic Cleveland Clinic

THOMAS E. STARZL, MD, PhD MARK SIEGLER, MD PAULINE W. CHEN, MD University of Pittsburgh School of Medicine University of Chicago Transplant Surgeon and Author Transplant innovation and ethical challenges: What have we learned7 A collection of perspectives and panel discussion

We have come far, but selecting organ recipients remains an ethical minefield By Denton A. Cooley, MD Only 40 years ago, on December 3, 1967, the world perfOlmed more than 1,000 cardiac transplantations was electrified by news of the first cardiac transplanta­ at the Texas Heart Institute. tion, performed in , , by the From the beginning, we were called upon to renowned Dr. Christiaan Barnard. identify appropriate donors and suitable recipients. We have progressed considerably since that time, but Although we rely on certain objective factors, such as not all issues have been settled. After several attempts age, weight, body size, gender, and blood type, many by Dr. and by Dr. Adrian Kant­ other issues must also be considered. Fortunately, rowitz in this country, we in Houston performed the the modem concept of brain death has now been first successful cardiac transplantation in the United accepted not only by the public and ethicists, but also States in April 1968. Initially we were impressed with by the legal community; in contrast, at one time it the results, and we embarked upon a very active car­ was considered homicidal to remove a beating heart. diac transplant program, performing as many as had I credit Christiaan Barnard with having the courage been done in total around the world. But after we had to remove a beating heart from a 26-year-old donor done some 15 or 20 cardiac transplants, the discourag­ who had suffered irreversible brain damage. Many of ing news began to emerge that the patients were not us had wanted to get into the transplant program, but surviving long: our longest survived for only 2 years. we could not identify a donor. As a result, our group in Houston, like others, The following case illustrates some of the other declared a moratorium on cardiac transplantation. ethical complexities that we continue to struggle The only group that continued throughout this era with today. was at Stanford University under Shumway, who had some success with immunosuppressive drugs. In the • CASE STUDY: A 17-YEAR-OLDWITH early 1980s, a new immunosuppressant, cyclosporine, AND A DESTRUCTIVE LIFESTYLE appeared that was used for , Several years ago, a 17 -year-old Latin American boy which reinvigorated us and others to use this drug came to our clinic in heart failure. He was very dis­ for cardiac transplantation. Since then, under the arming, but when we looked into his background we direction of my colleague, Dr. Bud Frazier, we have found that he had dropped out of high school after 1

Dr. Cooley is Founder, PreSident, and Surgeon-in-Chief of the Texas Heart Insti­ of Chicago, Il. Dr. Chen is the bestselling author of Final Exam: A Surgeon's tute at St. luke's Episcopal Hospital. Houston, TX. Dr. Fung is Chairman of the Reflections on Mortality (Vintage 2008) and a transplant surgeon most recently Departments of General Surgery and Hepato-pancreatic-biliary Surgery and on faculty in the Division of liver and at the University Director of the Transplantation Center at Cleveland Clinic. Dr. Young is Chair­ of California, los Angeles. man of the Endocrinology and Metabolism Institute, Director of the Kaufman All authors reported that they have no financial interests or relationships that Center for Heart Failure, and Chairman of the Academic Department of Medi­ cine at Cleveland Clinic. Dr. Starzl is Distinguished Service Professor of Sur­ pose a potential conflict of interest with this article. gery at the University of Pittsburgh School of Medicine and Director Emeritus This article was developed from an audio transcript of the panelists' presenta­ of the Thomas E. Starzl Transplantation Institute, Pittsburgh, PA. Dr. Siegler tions and a panel discussion. The transcript was edited by the Cleveland Clinic is the lindy Bergman Distinguished Service Professor of Medicine and Surgery Journal of Medicine staff for clarity and conciseness, and was then reviewed and Director of the Maclean Center for Clinical Medical Ethics at the University and revisedlapproved by each of the panelists and the moderator.

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year and was living with a girlfriend who was 2 months left atrium, and pumping it back into the aorta with pregnant by him and already had a 2-year-old child. a centrifugal pump. His heart began to recover, and The patient's cardiomyopathy was related to cocaine the device was removed after 72 hours. and alcohol abuse. Nevertheless, his stepfather was At this point he needed another transplantation. eligible for Texas Medicaid, and he was accepted for Our medical review board considered his eligibil­ cardiac transplantation. ity and turned him down, citing that others on our After the transplantation, he abided by the waiting list were more deserving of a transplant and immunosuppressive dmg regimen while he was under that retransplantation has a poorer success rate than our care. Then he moved to Fort Wayne, Indiana, initial transplantation. where Indiana Medicaid would not honor his Texas Medicaid coverage. So our hospital had to send him • EACH CASE POSES PROBLEMS, his immunosuppressive dmgs, which he used rather BUT A RECORD OF SUCCESS EMERGES sporadically. Although this patient could be viewed as a sort of While in Indiana, he was incarcerated for assault sociopath, he nevertheless is a young man who is and battery on his girlfriend. He began to have heart incapacitated and in need of heroic measures. His case failure but did not qualify to have the biopsies required illustrates the kind of nonmedical problems that face for proper study of rejection of his heart. He returned those of us who are actively involved in cardiac trans­ to our clinic and was scheduled for catheterization plantation. It can be very difficult to find solutions to the next day when he went into acute cardiac failure. the myriad social, economic, legal, and ethical issues. He had emergency late-night implantation of a per­ We perform about 50 transplants a year in our insti­ cutaneous ventricular assist device, which required tution, and every one of them has some issue. Never­ catheterizing the left atrium by perforating the inter­ theless, we just honored 25 patients who have survived atrial septum, taking the oxygenated blood out of the more than 20 years with cardiac transplantation.

Despite the odds, the transplant field has progressed rapidly By John J. Fung, MD, PhD Dr. Pauline Chen's clinical vignette [see previous We perform transplantations because we know article in this supplement] unfortunately still typifies that the alternative is prolonged morbidity and small bowel transplantation. One would not expect death. Knowing that we can provide a touch of hope to hear that kind of story today for a kidney or liver is why we move forward in this field. transplant, but in the early 19705 it was typical. The technology of transplantation has developed through aggressive scientific develop­ • 'WHY WOULD ANY YOUNG ments in the laboratory. It is fascinat­ If we had proceeded PHYSICIAN WANT TO GET ing that all this has developed in only INVOLVED IN THIS?' in a very stepwise 50 years. If we had proceeded in a very Dr. Cooley's comments about the manner, we probably stepwise manner, we probably would moratorium on cardiac transplanta­ w()uld not be even a not be even a tenth as far along in the tion brought back memories for me, tenth as far along in field as we are now. particularly from when I was studying the transplant field Heart, lung, liver, and kidney trans­ in the 1970s. as we are now. plantation are now all pretty routine. There was almost uniform mortality in ---:Dr. John Fung Intestinal transplantation is in the transplants performed in the late developing phase. The Cleveland and early '70s. One wonders why any Clinic is currently involved in facial young physician would have wanted to transplantation, which has some dif­ get involved in transplantation at that time. I was a ferent ethical issues related to identity. fellow training with Dr. at the Uni­ Everything in transplantation relates to ethics, versity of Pittsburgh and remember him saying, "Just from issues about using marginal donor grafts or make it work, then let everybody else figure out why." using beating-heart donors when someone has not I think that typifies the surgical mentality. been declared brain dead, to issues in patient selec-

S2 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 75 • SUPPLEMENT X MONTH 2008 tion, which often depends on social, economic (ie, exposure to health care providers was also substantial: insurance coverage), and psychosocial factors such as an average of 20 to 30 units of blood was used for a substance abuse and nonadherence issues. liver transplant. Patients who were HIV-positive were excluded from • ETHICAL INSIGHTS FROM TRANSPLANTS transplants even through the mid-1990s. I remember IN HIV-POSITIVE PATIENTS evaluating standard listing criteria for transplant An ethical area of particular interest to me that the recipients at a conference and hearing transplant sur­ Cleveland Clinic has also been involved with is geons say that HIV is an absolute contraindication to transplanting patients who are HIV-positive. This has transplant. I said, "Wait a minute, this is 1997; you always been an enigma: why would we want to trans­ cannot say that. Given that attitude, patients with plant an HIV-positive patient? Before the advent of HIV will never be transplanted." The New England antiviral therapies for HIV in the mid-1990s, mor­ Journal of Medicine had just published a major paper tality rates were very high, with patients suffering about the extent of survival in patients being treated miserable deaths from Kaposi sarcoma, the ]C virus with highly active antiretroviral therapy. leukoencephalopathies, and other debilitating oppor­ So we then started a prospective study of transplan­ tunistic infections. tation in HIV-positive patients, and long-term follow­ When I first arrived at the University of Pittsburgh up has shown that these patients can do very well. as a fellow, Dr. Starzl was telling us about this mys­ Interestingly, transplantation offers a new approach tery virus disease; when they retrospecti.vely analyzed to treating HIV-positive patients, in terms of immune specimens from organ recipients and donors, they reconstitution and the ability of immunosuppressive realized that HIV was being transmitted to patients agents to restore immune competency by preventing from donors as well as from blood transfusions. The the T-cell apoptosis initiated by HIV infection.

A continued need for evidence-based guidance By James B. Young, MD Speaking as the lone internist on this panel, and fewer heart transplants are being done in the also as a clinical trialist and evidence-based clinical United States in this decade than in the 1990s,2 practitioner, the greatest ethical challenge I see for in large part because other effective interventions transplantation is how to move the field forward in for heart failure have been developed. However, terms of garnering evidence that can the number of heart transplants is in help us treat patients and keep them fact on the rise again. 2 Second, sur­ Heart transplant is a bit alive. Nobody will deny that heart vival rates in heart transplant have transplantation is life-saving therapy: of a boutique science, improved substantially in recent my patients with end-stage ischemic so questions arise years compared with earlier eras, as cardi.omyopathy can be dramatically about how to evaluate it documented by registry data from transformed by a heart transplant after with the rigor of the International Society for Heart being near death. The questions now regulatory authority. and .l are how best to gain the data to guide -Dr. James Young Among other things, we have the next round of innovations in trans­ learned how to improve the opera- plant medicine and how to know when tion, better choose and preserve the time is right to attempt those innovations. , and better match hearts to recipients. We now can use hearts from older donors and allow • A HISTORICAL GLANCE AT older patients to undergo transplantation. One of Dr. Sharon Hunt, who was one of the first heart the keys to the better survival rates is a dramatic transplant cardiologists and worked with Dr. Nor­ change in the use of medications. Cyclosporine man Shumway, almost singlehandedly moved allowed for successful heart transplantation in the the field of cardiac transplantation forward. She 1980s, and we have since seen the advent of agents recently chronicled its history,l and this sort of such as tacrolimus, rapamycin, and mycophenolate historical review yields a couple of insights. First, mofetil. We rely less on the early immunosuppres-

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....------... Clinicalexperience (observation) "" ...... " 'PI""""" "'" "1" lh.ro""ti"oo~,,, """"

Research/Experimentation • Physiologic studies .. Basic .. ~ ,. Cfinical ...O(!-----. Observational series • Molecular biology pursued • Randomized trials • Disease paradigms evaluated • Systematic overviews Clinical treatment strategies developed 1.0( • Consensus identified t · Guidelines created Education .....1---- • Public . • Patients ~ • Health care providers Implementation FIGURE 1. Flow chart of • Health care providers evidence-based medical ~ .. • Health care systems practice. The drive for new knowledge is circuitous, Clinical practice beginning with clinical ~ ... • Individual patient treatment experience and observation and ultimately feeding back into clinical practice and ....------Assessment (accountability) further research prompted • Patient responses • Public health issues • Continuous quality improvement initiatives by new experience. sants, such as prednisone and azathioprine. demand a large randomized clinical trial? Despite these successes from a survival standpoint, How can we design clinical trials to help deter­ problems still need to be addressed. For instance, mine which direction to take in immunosuppression at 5 years, virtually every patient following a heart intensification or utilization protocols? Other chal­ transplant develops hypertension and dyslipidemia, 1 lenges include evaluating outcomes (such as coro­ in 3 has renal dysfunction (some requiring dialysis or nary artery vasculopathy) from databases, and then transplant), 1 in 3 has , and some develop a figuring out good and bad practices. For example, strange allograft arterioparhy.l databases show us that a donor history of diabetes increases the recipient's long-term risk of devel­ • THE CHALLENGE OF EVALUATING oping coronary artery vasculopathy.' Receiving a A BOUTIQUE SCIENCE heart from a male donor also increases risk. 3 Better Heart transplantation is a bit of a boutique science. understanding the panoply of adverse events and Although relatively few heart transplants are per­ what leads to better outcomes will give us a sense of formed compared with liver or kidney transplants, how to proceed and can drive the design of clinical heart transplantation is a dramatic operation limited trials. by many ethical challenges surrounding organ donor supply and utilization. • OTHER ETHICAL CHALLENGES As for any boutique science, questions arise From an ethical standpoint, how do we change prac­ about how to evaluate it with the rigor of regulatory tice? We have data on outcomes at 5, 10, and even authority-from both the Food and Drug Admin­ 20 years. The half-life of a heart transplanted today istration (FDA) perspective and the institutional is 12.5 years, whereas it llsed to be about 7 years. 3 review board ORB) perspective-without large clini­ Although it is clear that we have made progress, it is cal trials. Suppose that Dr. Cooley wants to make a a challenge to determine exactly how to make subtle minor modification in his immunosuppressive proto­ changes in practice, such as addressing polypharmacy col because of an observation of a high incidence of post-transplant. renal failure at the 5-year point; does that ethically Developing schemes that enable major innova-

84 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 75 • SUPPLEMENT X MONTH 2008 tion, particularly through coordination among problem of donor organ supply? medical and surgical teams, is another challenge. My perspective is that I believe in evidence-based For example, we are working with preservation medicine and in clinical trials. I believe we should techniques that use a beating heart for transplanta­ try to ethically move the field forward by taking a tion. From solid evidence based on animal models, clinical experience or an observation and moving it we believe this preparation can allow preservation through all the necessary elements of evaluation and of a heart for up to 12 hours. To some, that may treatment strategy development (Figure 1) to drive beg a number of questions: Why do we need to do a knowledge. I believe this applies to post-heart trans­ clinical trial in humans? Why does the FDA need to plant patients as much as it does to patients with regulate us? Why do we even need to answer to an conditions such as heart failure or ischemic heart IRB? Why not just make the change to alleviate the disease.

What does-and does not-spur innovation? By Thomas E. Starzl. MD, PhD • LESSONS FROM THE CODMAN ANALYSIS • PROGRESS DOES NOT ALWAYS REQUIRE OF FAILURES FULL UNDERSTANDING Dr. Ernest Codman was a Harvard Medical School Transplantation was first successfully performed in professor in the early 20th century who tried to intro­ the context of breaking through the donor-recipient duce a system of analyzing failures at Massachusetts genetic barrier on January 6, 1959, when Joseph General Hospital and other Harvard-affiliated hospi­ Murray and his team at the the Brigham Hospital tals. As a result, he was metaphorically ridden out of performed a kidney transplant using the patient's town on a rail. fraternal twin as a donor. This event was reproduced Codman recommended that complications and in Paris by Jean Hamburger and his team on June failures be classified as one of the following: 14, 1959, and then on three or four other occasions • An error in diagnosis in the next several years in patients who received • An error in judgment sublethal . This was at a time • An error in technique (if a surgical or a medical when no pharmacological immunosuppression was problem) available, so no follow-up treatment was offered. • An error in management. Astoundingly, the first case-the fraternal twin­ Only one escape hatch existed that did not indict lived for more than 20 years, and the French case for the surgical or medical team as culpable: the disease. 25 years, without ever being treated with immuno­ At the time, nothing could be done for many dis­ suppression. They were inexplicably tolerant. When eases, including cancer, heart disease, renal failure, immunosuppressive drugs were developed and sur­ and bowel insufficiency. vival rates improved, the questions around these early This is a type of analysis that can be brought to cases were never answered: Why did those transplan­ a mortality and morbidity conference and will not tations work? What were the mechanisms of engraft­ accept a lot of alibis; it forces the group to always ment? What was the relationship of engraftment to look at what could have been done to prevent a com­ tolerance? Without answering those questions, there plication or death. Some practitioners always want to was no way to make other big leaps in improvement blame some factor other than themselves: sometimes of what was already proved in principle-that is, the the patient, by being deemed noncompliant, is even feasibility of actually doing this kind of treatment. held responsible for his or her own complication or Improvements in patient and survival were death. dependent almost entirely on better drugs. I think the Codman analysis of failures is a good starting point for discussing innovations, especially • RANDOMIZED TRIALS HAVE A DUBIOUS since true breakthroughs come in those cases where RECORD IN TRANSPLANTATION the failure falls into the category of being caused by I know this will offend just about everyone here, but the disease itself, not by a medical or surgical error. I have no confidence in evidence-based therapy if And that is surely where transplantation falls. we are talking about randomized trials. None of the

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TRANSPLANT INNOVATION: WHAT HAVE WE LEARNED? .. great advances in transplantation has had anything dying and the central question was, "How can I treat to do with randomized trials. In my opinion, ran­ this patient?" They did laboratory research on their domized trials in transplantation have done nothing own to produce evidence that a new innovative idea but confuse the issue and have very nearly made it could work. I believe that if you have experiments impossible for the better immunosuppressants to be that show that you can keep a heart beating on a brought on board. Cyclosporine offered a tremendous preservation device for 12 hours, and you can put it step forward, but the randomized trials, carried out in a dog and it works well, that is the evidence you mostly in Europe, did not reveal much difference in need to proceed. How are you going to do a random­ outcome from treatment with azathioprine, at least as ized trial-hang on to an organ and let it beat for 12 assessed by patient and graft survival. The same thing hours just so it conforms with some protocol? That is occurred when tacrolimus emerged; randomized mul­ nonsense. ticenter trials actually delayed the widespread use of There was a period when clinical journals-Sur­ this superior drug for at least half a dozen years. gery of Gynecology and Obstetrics, Annals of Surgery, Annals of Internal Medicine, New England Journal • IN THE BIG PICTURE, of Medicine-published front-running discoveries. MONEY IS HOBBLING INNOVATION That ended about 25 years ago when it became more Earlier it was debated whether money drives every­ important to learn about details. The journals then thing. I do not believe that money became superfluous, and for another drives everything in medicine in reason as well: money drove the wheel Europe, and it certainly has little to do Randomized trials more and more. Hospital and program with driving improvements in Asia. in transplantation administrators expected the publica­ But money does drive everything in have done nothing tions to be advertisements, and the the United States, although the real but confuse the issue minute that articles started promot­ question is whether it has to be that and have very nearly ing something rather than report­ way. made it impossible ing facts, they lost value. Today the I believe that innovation is some­ for the better impact factors of the surgical journals how built within our genome. Many immunosuppressants are at about 2 or 3, meaning that their of the great advances in transplanta­ to be brought on board. articles are cited infrequently and tion, the elucidation of principles, -Dr. Thomas Starzl have have little real influence on the and the relatively recent discovery of practice of medicine. the mechanisms of alloengraftment How did we reach this point where were achieved without grant support. money drives everything? I think the The researchers involved could not have asked for page was turned in the very early 1990s, and it had to National Institutes of Health funding because their do with how medical practice is governed, especially ideas were so far out of the box that they probably in academic hospitals. Half of the health care in this would have been rejected or stolen. country is now provided by hospitals that are associ­ I wonder to what extent the vast amount of money ated with medical schools. Those hospitals and basic available for research is actually a disincentive for research laboratories contain our young people and genuine advancements. Part of the problem is that are where they will assimilate their ideals. If that the power of allocation is put in the hands of anony­ climate is not right, then we are raising the wrong mous peer-review committees. That system generates kind of doctors. droves of people to pursue money allocated to a cer­ Earlier researchers looked at a problem and tain area to learn more and more about less and less, thought, "Here's a question that has to do with this in the vague hope that acquiring enough details will patient before my eyes, and I must find some way result in a realistic concept. Sometimes the picture to solve it. Let's go to the laboratory." Today there simply becomes more confused. is a real danger that they are thinking, "I need to Another problem is that we have produced far advance my career, so let's see how I can get some more scientists than jobs, so that funding becomes the money. A little research will be a stepping stone to first priority because it is the only means of employ­ my professional development." Our discussion of ment. In earlier days, what drove people more often medical and surgical ethics today should take place was that they were confronted with a child who was within this framework.

S6 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 75 • SUPPLEMENT X MONTH 2008 Panel discussion Moderated by Mark Siegler, MD • WERE FINANCES A DRIVER OF EARLY to represent and protect them. I have also always felt TRANSPLANT INNOVATION? that those of us in these positions have an obligation to become innovators. Surgeons who merely see how Dr. Mark Siegler: It is clear that there are more many appendectomies or cholecystectomies they can and less ethical ways to introduce innovations. I am perform are being very derelict of their responsibility reminded of an article in JAMA by Francis Moore in to the institution. the late 1980s in which he warned that one of the things to look at for any new innovation was the ethi­ • MEASURING SUCCESS IN HEART TRANSPLANTATION cal climate of the institution.4 He cautioned us to be very aware of the driving force behind an innovation. Dr. Siegler: Dr. Cooley, what is the current success Is it to improve patient care? To save lives that oth­ rate for heart transplants? erwise would be lost? Or is it primarily for the self­ Dr. Cooley: Nationwide, around 90% of recipients aggrandizement of an investigator or the financial survive 12 months. Of those, maybe half are still alive goals of an institution? 5 years later. Of course, we do not know I also remember the chapter in Dr. what the future will hold. It is interest­ Starzl's book The Puzzle P eople5 about the ing that the first sign of rejection seems anguish involved in introducing liver Those of us privileged to to be coronary occlusive disease. It is transplantation. It seems that financial spend our entire career a different type of coronary occlusive considerations were not the driver of in academic settings, disease than is seen in atherosclerosis: major steps forward in introducing liver with institutions to it is diffuse, involving the entire extent transplantation, in Dr. Starzl's case, or represent and protect us. of the coronary circulation, and is not heart transplantation, in Dr. Cooley's have an obligation to really amenable to coronary bypass or case. Would you comment? become innovators. other interventional procedures. -Dr. Denton Cooley Dr. Thomas Starzl: Actually, not only Dr. Siegler: We are now at about the were we not driven by economic gain, 40th anniversary of the first human we expected financial penalty for focus- heart transplants, an extraordinary and historic inno­ ing on transplantation. If ever there was a field that vation. Dr. Cooley, do you think the timing was right developed against the grain, that was costly to people in 1968 when you did the first heart transplant in the who worked in it, whose engagement meant that for United States? In retrospect, would you have done most of their career they would work for substandard the first transplant sooner or maybe even a couple of income compared with their peers--even those peers years later? in academic medicine, let alone those in private practice-it would be transplantation. Dr. Cooley: You can argue it both ways. Should we It was not until 1973, when the end-stage renal have waited for further developments? At the time, disease (ESRD) program began under Medicare, that heart transplantation seemed to work fairly well in cash for transplantation started to become available. animals, but we never really know until it reaches the The real cash streams did not start until the middle clinical level. It was probably as opportune a time as to late 1980s when nonrenal organs became the cash any. We knew something about organ rejection at the cows. To be fair, no new technology can be assimi­ time, and we had immunosuppressive drugs, although lated into the health care system unless it at least they were not as effective as they are today. The news pays for itself. But you can go beyond that and create electrified the world. I think we were pretty well pre­ baronial kingdoms, and I think that is where you can pared for this spectacular event. go wrong. Dr. Siegler: When would have been the optimal time Dr. Denton Cooley: I would add that those of us to do a clinical trial in order to achieve evidence­ privileged to spend our entire career in academic set­ based medicine in heart transplantation? Would it tings have an opportunity that others may not have. have been during the big breakthroughs of Shumway, A lot of brilliant people in private practice are capable Barnard, and Cooley, or now, when we have the gen­ of doing many things but do not have an institution eral strategy and can find out how we can do better?

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Dr. J ames Young: I would not have done a random­ tat ion-the donor, the reCipient, and the patient ized trial at that time. The patients who were getting still on the waiting list because the organ went to the transplanted then were nearly dead; all other man­ recipient instead-also motivates the team with a agement was futile. In 1970, Life magazine listed the sense of obligation to the two unseen patients. 102 heart transplants that had been done around the If there is a lesson about the ethics of letting go, I world up to that point, and maybe only 2 or 3 of the think it is that we often fail to talk about these issues patients were still alive. That prompted the morato­ among ourselves. Perhaps if we had discussed end­ rium that Dr. Cooley referred to. of-life care or palliative care in Max's case, we might As ethical clinicians, we are supposed to do our have had more insight into the pressures we felt in best to make our patients feel better and make them considering the lives of three separate people. And live longer. Sometimes you have to do something rad­ those discussions might have-or might not have­ ical. On that basis, one can argue that we should not changed the situation. transplant "the walking wounded," that instead we should save organs for patients who are truly terminal Dr. Starzl: I agree completely with the preceding without some sort of ventricular replacement therapy. comments. All kinds of motivations might cause a But today we are getting away from transplanting only surgeon to cling too long-the ones that were men- dying patients, so we need randomized tioned as well as some ignoble ones, trials to find out how we are doing in such as vanity, in terms of looking at For my vintage of transplanting outpatients. That is the one's survival numbers. transplant surgeons, setting in which trials are now needed. I would also like to take a much death and failure are larger view. Some years ago in Colo­ • THE ETHICS OF 'LETTING GO' rarities and are truly a rado, the governor at the time, Rich­ Question from audience: Dr. Chen's sort of enemy, whereas ard Lamm, thought that intensive care story [see previous article] raised the prior generations of units (ICUs) were harmful-that they issue of the ethics of "letting go" of surgeons are wiser and were economically draining, did not one's patient. I wonder if in transplan­ perhaps have a better serve society, and prolonged suffer­ tation, especially when innovative pro­ sense of when it is time ing. My position, which was really the cedures are involved, a commitment to to stop intervening. opposite, was that maybe he was right the procedure itself might sometimes -Dr. Pauline Chen in his philosophy but transplanta­ conflict with the need to let go of the tion had, in a sense, changed all that. patient. Transplantation took desperate people who were in the ICU, with no chance Dr. John Fung: In the United States, we measure of coming out, and dramatically returned them to efficacy and benefits in different ways than people wonderful health. do in other parts of the world. Here, for a child with As procedures get better, this scenario happens a biliary atresia-the most common reason for liver more and more often. I agree that there is a time transplantation-we expend hundreds of thousands when you realize that no intervention will work and of dollars for a liver transplant, which is usually able you should stop treatment. That is a bitter pill. But it to save the child's life. But in China, a severely ill is very hard to define when that moment occurs. child is viewed as a medical and economic liability and will be allowed to die so the family can have Dr. Chen: There also may be somewhat of a genera­ another child. tional difference in approach. It is also not only the ethics of letting go. We all Most surgeons will fully acknowledge that they deal with letting go, not just in transplant medicine. stand on the shoulders of giants, and that holds par­ It is also the ethics of actually getting a patient into ticularly true in a field like transplantation. When the system. In the case of transplanting a newborn, I was training in liver transplantation, for example, as in Dr. Chen's narrative, should they even have 80% to 90% of the patients could fully expect to sur­ embarked on that? vive 5 years. For my vintage of surgeons, then, death and failure were rarities and they were truly a sort of Dr. Pauline Chen: For me, the story illustrates the enemy, whereas surgeons like Dr. Starzl and Dr. Cooley remarkable connection and profound attachment have seen so much more and are far more used to all between a surgeon and his or her patient. The fact the variations of outcomes. Because of that breadth of that three patients are really involved in transplan- experience that you have, I think you are wiser than

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