By Elaine Chen, MD
Assistant Professor, Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Section of Palliative Medicine, Rush University Medical Center, Chicago
Dr. Chen reports no financial relationships relevant to this field of study.
She was 21 years old, and the first in her family to go to college. She had asthma that was generally well controlled. That day, she had been exposed to an extra amount of dust as she helped her friends pack up for their move. She went home and started wheezing. She reached for her albuterol inhaler and pumped, and pumped, but nothing came out. The inhaler was broken; her neighbor’s dog had chewed it. She called for help. The neighbor called 911, and an ambulance came quickly. But it was too late. By the time she arrived at the hospital, there was irreversible brain damage. Over the next few days, it became clear that she had died. Her family agreed that she would want to be an organ donor, and she was able to donate her kidneys, liver, pancreas, lungs, and heart. This is the case of a patient I cared for, only one of the myriad heartbreaking yet inspiring stories of organ donors, many of which can be found on donation and transplantation websites.
Organ transplants are amazing and lifesaving treatments. In 2018 in the United States, 36,528 organ transplants were performed. This number has been increasing steadily, and more than 750,000 transplants have taken place since 1988. However, 6,140 people died in 2018 while awaiting a transplant, and more than 113,000 people currently are awaiting transplant; this number has been increasing at a much more rapid rate than the number of donors and transplants.
Organ donors may be living or deceased. In 2018, organs were recovered from 17,568 donors, of which 10,721 were deceased donors and 6,847 were living donors. Of the deceased donors, 8,589 donations occurred after neurologic death and 2,132 occurred after cardiac death.1 Deceased organ donors have the potential to donate kidneys, liver, lungs, heart, pancreas, and intestines, in addition to corneas and tissues. Since 2005, hands and faces have been transplanted in complex surgeries called vascularized composite allograft (VCA) transplants that include grafting of bone, muscle, nerve, skin, and blood vessels.2 Approximately 58% of adults in the United States are registered as organ donors on state registries,3 up from 46% in 2010.4
The first successful solid organ transplant was a kidney transplant that took place in Boston in 1954. This transplant was followed by successful liver, heart, and pancreas transplants in the 1960s, and lung and intestine transplants in the 1980s. Laws and policies in the United States have evolved to support transplantation. In 1968, all 50 states adopted the Uniform Anatomical Gift Act (UAGA). It was the first national law passed to regulate transplantation; prior to that, the laws varied substantially from state to state. This was further strengthened in 1972, when uniform donor cards were recognized as legally binding in all 50 states.
In 1984, Congress passed the National Organ Transplant Act. This act called for an Organ Procurement and Transplantation Network to be created and run by a private, nonprofit organization under federal contract. The United Network for Organ Sharing (UNOS) was established and awarded the OPTN contract in 1986 by the U.S. Department of Health and Human Services; UNOS has held this contract continuously. Organ procurement organizations (OPOs) are regionally run nonprofit organizations that manage and coordinate the evaluation and procurement of deceased donor organs for transplant. Currently, the United States has 58 OPOs, all of which are certified by the Centers for Medicare and Medicaid Services, members of UNOS, and the Association of Organ Procurement Organizations. The OPO is the front-line contact with the hospital and the family of the potential donor and coordinates with the transplantation team.2,5 In 2015, the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations published a joint consensus statement with recommendations for the management of the potential organ donor.3
Organ Donors in the Intensive Care Unit
The ICU is important in the consideration of organ donation because all deceased donors enter the ICU at some point during treatment. Whether donation occurs after determination of death by neurologic or circulatory criteria, those patients are maintained on life support, including mechanical ventilation. The intensivist is of utmost importance, caring for the patients both before and after organ donation is considered, and collaborating with the OPO. In the setting of catastrophic brain injury, the intensivist’s initial goal is to optimize cerebral perfusion. However, if restoring neurologic function is deemed impossible, the intensivist’s goals shift to include maintaining hemodynamic stability, preparing the family for devastating news, counseling them on end-of-life issues, and preserving the option of organ donation.
In 2011, Singbartl et al from the University of Pittsburgh showed that an intensivist-led donor management program for all consented adult brain-dead patients led to a significant increase in the number of transplantable organs recovered, highlighting the importance of intensivist collaboration with the OPO.6 In their retrospective analysis, in the one year before the program began, 66 of 210 potentially available organs from 35 decedents were recovered. These numbers increased to 113 of 258 potentially available organs from 43 decedents. The significant increases were seen in kidney and lung transplants, specifically, but because of the small number of donors, specific contributing factors could not be identified.
There are two methods for determining death prior to transplantation: by neurologic or circulatory criteria. Traditionally, the phrases and acronyms “donation after brain death” (DBD) and “donation after cardiac/circulatory death” (DCD) were used to describe donors. However, because there were many colloquial and lay misinterpretations of the phrase “brain dead,” the newer terms “death by neurologic criteria” (DNC) and “neurologic determination of death” (NDD) are preferred by neurologists and intensivists. Neurologic determination of death has not been without controversy, and many physicians are not comfortable with the complex process of examination and testing. This is complicated further by variability in standards among practice sites and evolving criteria requiring physicians to keep up to date on the criteria.7 Determination of death by neurologic criteria should adhere to the recommendations provided by the Quality Standards Subcommittee of the American Academy of Neurology, which were developed in 1995 and updated and revised in 2010.8 They include a checklist for clinical examination, methods of ancillary testing (including cerebral angiography, electroencephalography, transcranial Doppler ultrasonography, and cerebral scintigraphy), and an apnea test. Despite these detailed recommendations, differences in the practice of NDD still exist, such as the number of physicians required, the type and need for confirmatory tests, and the performance of the apnea test that can vary by institution, and as well as among and within countries.
Deceased donors who have devastating clinical conditions but do not fulfill criteria for DNC may have the option for donation after withdrawal of life support. Donation after death by circulatory criteria (DCC) or circulatory determination of death (CDD) involves a separate and complex set of challenges. This pathway has the potential to recover kidneys, livers, pancreases, and even lungs and hearts for transplant. Transplant outcomes associated with CDD donors and NDD donors are similar overall, but may be more challenging, costly, and time-consuming with CDD donors.3 For instance, kidney transplants have a higher prevalence of delayed graft function, and lung grafts may undergo a process of ex vivo “conditioning” between recovery and implantation to improve function. Many institutions have developed standardized protocols for this process, which includes transferring to an operating room and monitoring hemodynamic criteria, followed by withdrawal of life support. Generally, patients are monitored following withdrawal; if circulatory cessation occurs within 60 minutes, then organ procurement occurs. If death by circulatory criteria does not occur within 60 minutes, then the patient is returned to the ICU for further comfort measures.
Predicting the time to death in potential donors after CDD is crucial for selecting candidates. Many studies and tools have proposed various methods of assessing the prognosis after withdrawal of life support. A UNOS DCDD consensus committee developed and validated criteria for prediction of death within 60 minutes. Of the 533 patients studied, a total of 29%, 52%, 65%, and 82% of patients with zero, one, two, and three criteria, respectively, died within 60 minutes of life support withdrawal.9 A Dutch study found that intensivist prediction of death within 60 and 120 minutes, independent of any prediction tools, had a sensitivity of 73% and 89%, with a specificity of 56% and 23%.10 Guidelines recommend using scoring systems together with expert clinician judgment for the selection of appropriate candidates. Although there is no specific threshold recommendation for the number of successful cases, an increased number of unsuccessful cases must be acceptable to maximize the number of potential donors.
Interactions with families and the OPOs involve sensitivity and complex communication skills. Early notification of the OPO is essential and should be standardized as much as possible to provide all patients with equal opportunities for organ donation. Notification of brain death need not be separated from discussions of organ donation. However, while organ donation can be a consideration in end-of-life discussions, decisions for withdrawing life-sustaining therapies should be separate from decisions to donate organs.11 As a result of the UAGA, first-person authorization provides sufficient grounds for organ procurement, and surrogates are prohibited from overriding such consent.3
In the absence of first-person authorization, OPO representatives or designated requestors collaborate with the healthcare team to request family or surrogate authorization for donation. Siminoff and colleagues demonstrated significantly higher conversion rates when the requesting personnel had substantial experience and interest in helping families navigate the organ donation process, when families had more contact with the OPO, and when efforts between the requestor and the primary clinical team were well coordinated.12
Potential donors with certain clinical conditions are less optimal candidates. For example, cancer transmission from donor to recipient has been documented. In one retrospective study of 296 donors who were found to have malignancy, researchers found that choriocarcinoma, melanoma, lung cancer, and renal cell carcinoma all had a high rate of transmission greater than 40%.13 In contrast, in a 2007 UNOS database report, there were no cases of transmission of any tumor other than malignant melanoma, including breast, lung, ovarian, and colon cancers.14 However, in this report, tumor stage was not provided, and many donors had been cancer-free for more than 10 years. Thus, transplanting any donor with melanoma is not recommended, but there are no absolute contraindications to organ donation from a cancer patient. However, the risk of transmission must be weighed against the risk of not receiving a transplant. Patients with active bacteremia, sepsis, and bacterial meningitis can be considered for donation, but delaying procurement to allow for at least 24-48 hours of appropriate antibiotics is recommended. Patients with an undiagnosed febrile illness, encephalitis, meningitis, or flaccid paralysis should not donate their organs because of reports of transmission of rabies virus and lymphocytic choriomeningitis virus that were discovered after recipients fell ill. HIV positive status is considered an absolute contraindication for donation to HIV-negative recipients. Seronegative patients at risk for HIV can be considered for donation after nucleic-amplification testing for HIV RNA, with an understanding that a small risk for occult infection still exists.3
Once DNC has been determined or donation after DCC is being considered, maintaining adequate perfusion of organs is important for optimizing the number of potentially transplantable organs. Hemodynamic alterations often accompany DNC. Volume resuscitation with isotonic crystalloid is recommended to maintain euvolemia.3 Dopamine is the preferred first-line vasoactive agent in the pre-procurement period, because of its inotropic and vasopressor effects. Dopamine is associated with improved outcomes in kidney transplantation.15,16 It is preferred over norepinephrine and phenylephrine because the alpha-agonism in these drugs predisposes to increased pulmonary capillary permeability, leading to increased pulmonary edema as well as coronary and mesenteric vasoconstriction. Vasopressin counteracts diabetes insipidus and improves organ recovery rates. Often it is used as the second-line, or even first-line, agent in hemodynamic management after DNC.17
Care of the Donor and Family After the Donation Attempt
For families, the organ donation process does not end after donation is authorized or even after organs are procured. For successful donations, the grieving family and friends need care. The OPO provides bereavement care and other support to the families of each donor and follows up with letters documenting the progress of organ recipients.18 In DCDD cases, if death does not occur within 60 minutes, the patient returns to the ICU, and comfort care resumes. Hospice should be an available option for these patients, since survival can range from hours to days or even weeks.
Organ donation and its attempt can lead to significant benefits and challenges to the donor family. In 2007, Merchant and colleagues studied the post-donation psychological sequelae of organ donation. They surveyed Canadian donor families about their bereavement experience, including depression, post-traumatic stress, and the donation experience. Of 196 questionnaire packages mailed, 73 were returned. The authors found an overall positive impression from donor families about the donation process and that donation may have a beneficial effect on the bereavement process. Those who viewed the donation process positively and felt comforted by the donation process reported fewer symptoms of depression.19 Conversely, attempted but unsuccessful donation after circulatory death can lead to harm.
Taylor and colleagues conducted face-to-face interviews with 15 family members who had direct experience with unsuccessful DCD.20 They described a broad spectrum of harm associated with unsuccessful donation, including the waste of precious organs, a lost opportunity to honor their loved one, and an inability to harness comfort from donation to ease their grief. Family members also reported distress and disrupted bereavement as a result of unsuccessful donation, as well as difficulty understanding the difference between brain death and cardiac death. However, they felt that the harms were worth the benefits of trying to donate.
Organ donation and transplantation are important and lifesaving procedures. The processes have undergone significant clinical and legal evolution since the first successful organ transplants in the 1950s and 1960s, and demand for organs continues to outpace availability. The process involves collaboration from intensivists, neurologists, and OPOs, with both regional and national oversight. The complexities of management include determination of death, communication with families, pre-procurement optimization of potential donors, and bereavement support for families, especially after an unsuccessful donation attempt.
- Based on OPTN data. Available at: . Accessed Sept. 1, 2019.
- U.S. Government Information on Organ Donation and Transplantation. Health Resources & Services Administration. Available at: . Accessed Aug. 31, 2019.
- Donate Life America web site. Available at: . Accessed Aug. 27, 2019.
- Kotloff RM, Blosser S, Fulda GJ, et al. Management of the potential organ donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement. Crit Care Med 2015;43:1291-1325.
- United Network for Organ Sharing. Available at: . Accessed Aug. 31, 3019.
- Singbartl K, Murugan R, Kaynar AM, et al. Intensivist-led management of brain-dead donors is associated with an increase in organ recovery for transplantation. Am J Transplant 2011;11:1517-1521.
- Braksick SA, Robinson CP, Gronseth GS, et al. Variability in reported physician practices for brain death determination. Neurology 2019;92:e888-e894.
- Wijdicks EF, Varelas PN, Gronseth GS, Greer DM. Evidence-based guideline update: Determining brain death in adults: Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2010;74:1911-1918.
- DeVita MA, Brooks MM, Zawistowski C, et al. Donors after cardiac death: Validation of identification criteria (DVIC) study for predictors of rapid death. Am J Transplant 2008;8:432-441.
- Wind J, Snoeijs MG, Brugman CA, et al. Prediction of time of death after withdrawal of life-sustaining treatment in potential donors after cardiac death. Crit Care Med 2012;40:766-769.
- DuBois JM, DeVita M. Donation after cardiac death in the United States: How to move forward. Crit Care Med 2006;34:3045-3047.
- Siminoff LA, Gordon N, Hewlett J, Arnold RM. Factors influencing families’ consent for donation of solid organs for transplantation. JAMA 2001;286:71-77.
- Buell JF, Beebe TM, Trofe J, et al. Donor transmitted malignancies. Ann Transplant 2004;9:53-56.
- Kauffman HM, Cherikh WS, McBride MA, et al. Deceased donors with a past history of malignancy: An organ procurement and transplantation network/united network for organ sharing update. Transplantation 2007;84:272-274.
- Schnuelle P, Gottmann U, Hoeger S, et al. Effects of donor pretreatment with dopamine on graft function after kidney transplantation: A randomized controlled trial. JAMA 2009;302:1067-1075.
- Schnuelle P, Benck U, Yard BA. Dopamine in transplantation: Written off or comeback with novel indication? Clin Transplant 2018;32:e13292.
- Plurad DS, Bricker S, Neville A, et al. Arginine vasopressin significantly increases the rate of successful organ procurement in potential donors. Am J Surg 2012;204:856-860.
- Association of Organ Procurement Organizations. Available at: www.aopo.org. Accessed Sept. 1, 2019.
- Merchant SJ, Yoshida EM, Lee TK, et al. Exploring the psychological effects of deceased organ donation on the families of the organ donors. Clin Transplant 2008;22:341-347.
- Taylor LJ, Buffington A, Scalea JR, et al. Harms of unsuccessful donation after circulatory death: An exploratory study. Am J Transplant 2018;18:402-409.