This essay is part I of a two-part series.
Medical interventions and technologies have always inspired both feelings of awe and dread. Organ transplantation (OTx) is similar in this respect, but it also raises the stakes from the point of view of all four principles of biomedical ethics. The first successful human kidney transplant was performed by Dr. Joseph Murray in 1954 (70 years ago) between identical twins. The graft survived eight years. Murray was awarded a Nobel Prize for this accomplishment. Expansion of solid transplants to include other organs and between unrelated patients began in the 1960s, but feasibility and success was established in 1983 with the development of the immunosuppressive agent Cyclosporine A. Prior to this, the regimens for immunosuppression were minimally successful and fraught with side effects. The discovery of Cyclosporine allowed rapid growth of organ transplant programs. However, organ transplant still faces the challenge of the mismatch between organ supply and demand. There are currently over 100,000 patients waiting for transplants on the Organ Procurement and Transplant Network (OPTN) waiting list in the United States; over 80% are waiting for kidney transplants.
The Uniform Determination of Death Act codified two legally recognized ways of declaring or determining death – death by neurologic criteria, and death by irreversible loss of respiratory or circulatory function (DCD). Although the latter constitutes the vast majority of deaths, until the past decade, organ recovery for transplant was most often performed following neurologic, or brain death criteria (DND). In recent decades, the use of living donors has increased the organ supply for kidney transplants, in addition to some liver and lung recipients, the supply is still inadequate to meet the needs of potential organ recipients. To meet the demands for organs, there has been a focus on trying to expand the potential donor pool. Over the past decade there has been increased focus on controlled donation after circulatory determination of death (cDCD). These are individuals with a devastating brain injury deemed unlikely to recover, but still have some brain stem function, and cannot be declared “brain dead” and has become increasingly common with the increase in opiate overdose deaths within the US. In these potential donors, life sustaining therapies, typically mechanical ventilation is stopped, with the intention of allowing their death by circulatory criteria; if death occurs within 30-60 minutes organs can be recovered. Use of organs from cDCDs has increased the donor pool by upwards of 30%.
The shortage of organs for transplants has led to considerable controversy about allocation of organs. For decades, United Network for Organ Sharing (UNOS), a not-for-profit corporation that has maintained the OPTN contract, consulted physicians and established policies that allocated organs within the boundaries of an organ procurement organization (OPO), then within 11 regions for some organs, or within 500 nautical mile zones for hearts and lungs. Health Resources and Service Administration (HRSA) published a Final Rule in 2000 based on an Institute of Medicine study that recommended organs be allocated based on disease urgency (risk of death on the waiting list) while minimizing futile transplants, and minimizing impact of waiting time and geography, within limits of ischemic time. UNOS resisted the requirement to change organ allocation. One of the co-authors (T.E.) served on the OPTN Thoracic Organ Committee, leading to implementation of a new way to allocate donor lungs, based on a Lung Allocation Score (LAS). The LAS algorithm was based on predicted survival on the waiting list without alung transplant, and predicted risk of death within the first year after lung transplant, based on pre-transplant data. The LAS system successfully reduced waitlist deaths and increased the number of lungs accepted for transplant.
Procurement of organs from donations after circulatory death raises a new set of ethical issues; the most prominent is how organs are procured from controlled donation after circulatory death. There are currently two accepted methods, direct procurement quickly after death declaration, followed by machine perfusion, and normothermic regional perfusion (NRP). Currently there is no consensus about the ethical status of these methods, specifically for NRP involving thoracic organs (Thoraco-abdominal, or TA-NRP). Using direct procurement, the heart and other organs are removed from the donor and placed on external machine perfusion devices, whereas with the TA-NRP, the donor is placed on an extracorpoeal membrane oxygenation circuit after the cerebral blood vessels are clamped, and theorgans are perfused within the donor body.
The use of organs recovered from donors after circulatory death also brings to light an area that has been historically overlooked, namely that of donor rights. What are the ethical responsibilities to honor either the previously expressed wishes of a potential organ donor, or those of their families? The amended Uniform Anatomical Gift Act has been passed in all states, and essentially authorizes organ recovery after death from registered organ donors. It has equivalent authority as an advanced directive. Specifically, it removes next-of-kin (NOK) from the decision to donate organs. Does use of these organs then allow either testing of strategies to improve organ graft survival, and with that, organ recipient survival? And who decides, or rather who should engage in the conversations about contest for such testing? These are uncharted ethical fields within organ transplantation.
Dr. Veljko Dubljevic is a Professor of Philosophy and STS (Science, Technology and Society) at North Carolina State University and also leads the NeuroComputational Ethics Research Group.
Dr. Thomas Egan is a Professor of Surgery at UNC Chapel Hill, Adjunct Professor in the joint UNC/NCSU Dept of Biomedical Engineering.
Dr. Savitri Fedson is a Professor of Medicine and Clinical Ethics at the Michael E. DeBakey VA Medical Center and Baylor College of Medicine and a transplant cardiologist.
Dr. William Rand is a Professor of Marketing and Analytics and Executive Director of Business Analytics Initiative at North Carolina State University.
Dr. Munindar P. Singh is a Professor of Computer Science at NC State University.