Organ Failure and Transplantation

Overview

Solid organ transplantation is an accepted, successful, and commonly employed treatment option for patients with end-organ failure. Transplantation recipients of a heart, liver, kidney, lung(s), pancreas, or small intestine now live longer with an overall improved quality of life. Transplantation now also offers hope to patients with severed upper limbs and to those who have suffered facial disfigurement. Progress in the development of immunosuppressive medications and in methods of organ procurement and distribution has also enabled transplantation. Former contraindications to transplant, such as a history of cancer or HIV infection, are no longer absolute barriers.

In the United States, the United Network for Organ Sharing (UNOS), a non-profit organization endowed by Congress but reporting to the Department of Health and Human Services, regulates the allocation and distribution of donor organs. UNOS has two branches: the Organ Procurement and Transplant Network (OPTN) and the Scientific Registry of Transplant Recipients (SRTR). The OPTN divides the country into 11 distinct geographic regions or donation service areas (DSA) and each region has its own waiting lists. Allocation of organs generally follows local, regional, and national progress, where local refers to the boundaries of the DSA. The length of time that a transplant candidate spends on a waiting list, regardless of organ, can differ greatly among regions.

The method of determination of a transplant candidate's place on a waiting list is organ-specific. For kidneys, “time served” on the waiting list is the primary determining factor. Potential pediatric recipients (age 18 years and younger) for both kidneys and livers take priority over adults. In 2014, OPTN/UNOS Kidney Transplantation Committee implemented new guidelines for adult transplant candidates taking into account a candidate's Estimated Post-Transplant Survival (EPTS) and creating a measure of kidney quality or the Kidney Donor Profile Index (KDPI) in an effort to optimize the match between donors and recipients. The Lung Allocation Score (LAS) is a calculated score for patients over 12 years of age that identifies, among other things, the severity of illness and the likelihood of a successful transplant outcome. The score undergoes frequent modifications based on several factors, including shifts in the characteristics of the candidate cohort, with the consistent goal of reducing time spent on the waiting list. That score, in addition to other factors, includes age, blood type, and geographic location, and determines waiting-list placement for potential lung transplantation recipients. OPTN limits the allocation of lungs to patients less than 12 years of age to donors within the same age range. This policy has come under scrutiny due to a highly publicized case, in which the parents of a 10-year-old girl appealed to a federal judge to allow the patient access to lungs from the adult donor pool. Increasingly, patients with acute respiratory failure have been placed on an extracorporeal membrane oxygenator (ECMO) as a bridge to transplant. The Model for End-stage Liver Disease (MELD) is also a calculated score that predicts how urgently a patient over 12 years of age will need a transplant within the next 3 months. The only exception to the MELD system is a special category known as “Status 1.” Status 1A patients have suffered acute hepatic failure and might die within hours or days without a transplant ( Tables 29-1 and 29-2 list the LAS and MELD criteria). Since 1999, heart transplant recipients have received organs based on medical urgency; in 2005, UNOS/OPTN implemented a modification to that policy in terms of geographic sharing of organs. In 2012, it became clear that the current allocation policy was not sufficient based on the number of critically ill candidates who are not able to receive transplants. The heart subcommittee of UNOS/OPTN is now attempting to modify these guidelines and is engaged in an ongoing discussion about the most equitable way to distribute donor hearts.

Several factors limit the success of organ transplantation. Allograft rejection and the complications of anti-rejection therapy also continue to limit successful transplantation. In addition, immunocompromised hosts are vulnerable to bacteria, viruses, and fungi that are not considered pathogenic in the normal population. Finally, the side effects of immunosuppressive medications that are used to manage rejection can be debilitating, disfiguring, or life-threatening, and increase the risk for neoplasm, problems with bone metabolism, a cushingoid body habitus, nephrotoxicity, posterior-reversible encephalopathic syndrome (PRES), and the development of diabetes mellitus.

The most pressing challenge, however, remains the shortage of available deceased-donor and living-donor organs. The scarcity of cadaveric organs creates a mismatch between the number of patients who need transplantation and the number who can undergo transplantation. In 2015, there were approximately 30,000 transplants performed in the United States; almost 25,000 were from deceased donors and 5000 from living donors. Kidney and liver transplants comprised the majority with approximately 18,000 and 7000, respectively. The remainder included heart, lung, and pancreas. In recent years, transplant centers have attempted to expand the donor pool by harvesting organs from donors after circulatory death (DCD) in addition to harvesting organs from persons who have been declared dead by neurological criteria (i.e., brain death). The recent changes in how deceased-donor kidneys are distributed, noted above, have helped to increase the number of patients who are “difficult to match” getting a transplant. But, there are still more than 101,000 patients on the national kidney transplant waiting list in 2017.

Organ donation by living donors is an increasingly important potential source of transplantable kidneys, livers, and lungs. This is especially true in Japan where there are no defined criteria for determination of brain death and therefore few cadaveric organs are available for harvest. In the United States, living donors may be: related to the recipient; unrelated but emotionally connected; or anonymous, altruistic strangers. According to data from OPTN (from 2015) 24,980 transplanted organs came from deceased donors and 5989 organ transplants came from live donors. Parent-to-child liver transplantation (of the left lateral lobe) is an option, as is adult-to-adult transplantation of the right hepatic lobe. Living-lung donation is also an option for carefully selected candidates, but it requires a lower lobe from two different donors for each single potential recipient. The source of the donated organ (i.e., from a deceased donor or living donor) does not affect recipient outcome.

Living organ donation raises several ethical questions: What is true informed consent regarding both short- and long-term risks for the donor? Is the donor's offer (be it from an emotionally connected or unrelated person) truly voluntary? It is difficult to determine what level of risk is acceptable for a healthy, altruistic donor.

Several retrospective studies of the long-term medical and psychological sequelae in living organ donors have been conducted. Short-term risks for live kidney donors include the morbidity secondary to surgery and anesthesia (e.g., bleeding, infection) and salary loss during the weeks of recovery. For kidney donors, long-term health risks include the development of microalbuminuria and the potential for renal failure in the remaining kidney. Very recently, researchers created a model to estimate a potential kidney donor's long-term risk of developing end-stage renal disease (ESRD) without donation that they hope will be helpful in advising potential donors. The mortality rates for kidney donors is 0.03%; with adult-to-adult liver donation there is a significant degree of morbidity, and mortality rate estimates approach 0.1% for left lateral donation and 0.5% for right lateral donation. To date, no deaths have resulted from living lobar lung donation. One study found that donors lose 15% to 20% of their total lung volume and often experience a decrease in exercise capacity. Another study demonstrated that both the forced vital capacity (FVC) and forced expiratory volume at 1 minute (FEV1) returned to 90% of baseline at 1 year post-lobectomy.

Psychiatric Evaluation of the Transplant Patient

Psychiatrists and other mental health professionals are involved in many different aspects of the transplantation process. In some centers, a designated psychiatrist works with a specific team: for example, the kidney transplant team. Other transplant centers rely on general hospital psychiatric consultation services, psychologists, or social workers to provide case-by-case consultation. The involvement of mental health professionals ranges from the preoperative evaluation of candidates and living donors, to the short- and long-term postoperative management of solid organ recipients.

The psychiatrist or other mental health professional plays an important role in the evaluation of the patient who is approaching a transplant. Initially, the psychiatrist conducts a thorough psychiatric evaluation of the potential recipient to determine suitability for transplant. The psychiatrist must be familiar with medical and surgical problems facing the patient (both before and after transplantation), in order to educate both the patient and the family members about the risks and benefits of transplantation.

The psychiatrist may also act as a liaison between the patient (and family members) and the transplant team. The patient will need support, direction, and clarification of the transplant team's expectations and concerns. The transplant team may require help interpreting a patient's behavior. The psychiatrist can direct the team's attention on ethical dilemmas that may arise, particularly in the area of directed living donation by a related or unrelated donor.

After transplantation, the psychiatrist will be instrumental in guiding the family through the patient's often difficult and unpredictable postoperative course, as well as in managing the neuropsychiatric sequelae secondary to graft rejection, infection, and immunosuppression.

Psychiatric Considerations in Patients With End-Organ Failure

Many psychiatric disorders (such as depression, anxiety, adjustment disorders, post-traumatic stress disorder [PTSD], and substance abuse) are common in the pre-transplant candidate population, regardless of the type of end-stage organ failure. Other disorders are unique to patients who suffer from a particular type of end-organ failure. Usually, there is a significant wait between the time of listing for transplant and the transplant itself. Many patients with heart failure must wait in a hospital's intensive care unit (ICU) attached to a cardiac monitor or an intra-aortic balloon pump (IABP); others live outside the hospital with left ventricular assist devices (LVADs). Years can go by while the patient with lung disease waits at home, sometimes far from a transplant center, becoming gradually sicker and more sedentary, all the while tethered to an oxygen tank. The wait is stressful. A call from a member of the transplant team saying that an organ is available can come at any time or not at all. Sometimes a patient arrives at the hospital only to learn that the quality of the harvested organ is not good enough—the so-called “false start” or “dry run.” Loss of physical strength and productivity (with accompanying role change within the family or community) can lead to an adjustment disorder or to depression.

As many as 25% of dialysis-dependent patients with ESRD manifest symptoms of clinical depression. Disorders of endocrine function (e.g., hyper-parathyroidism), and chronic anemia can also contribute to depression. The dialysis-dysequilibrium syndrome with resultant cerebral edema, as well as uremia, can precipitate a change in mental status or even a frank encephalopathy. Patients with renal failure are prone to delirium from the accumulation of toxins (e.g., aluminum) or prescribed medications that are normally cleared through the kidney.

Patients with cardiac failure are also at risk for depression and delirium. These patients can spend long periods in the ICU awaiting transplantation with little contact with the outside world. Delirium can be caused by decreased cerebral blood flow, by multiple small ischemic events, or by IABP treatment. The development of the LVAD as a bridge to heart transplantation offers a chance for improved quality of life and functional status in this population. LVAD implantation as a bridge to transplant (BTT) confers a survival benefit for transplant candidates compared with those who are managed medically. LVAD can also be used as a bridge to candidacy (BTC) as implantation can stabilize a patient long enough for him/her to address other issues that preclude transplant candidacy, such as weight and possibly cardiac-induced pulmonary hypertension.

Hepatic failure (e.g., from cirrhosis) is also associated with a high degree of depression and subclinical or frank encephalopathy. Treatment of the mood disorder can result in a more positive outlook and in better self-care. Suicide attempt by toxic ingestion (e.g., of acetaminophen) can result in sudden, drastic, hepatic failure and in an immediate need for transplantation. These patients are more difficult to assess because they are often on ventilators. The psychiatric consultant must therefore rely on collateral sources of information about the patient's pre-morbid function.

Patients with end-stage lung disease are likely to suffer from anxiety disorders, particularly panic disorder, in addition to adjustment disorders, depression, and delirium. Most patients who are not anxious pre-morbidly become anxious in the setting of increasing shortness of breath. They often describe anticipatory anxiety (in the setting of planned exertion), panic attacks, and agoraphobia, despite adequate oxygen supplementation. A decreasing radius of activity leads to both adjustment disorder and, sometimes, major depression, as patients struggle to cope with their relentless and progressive inability to perform even simple activities of daily living (ADLs).

Extremely compromised patients with pulmonary failure may become delirious from hypoxia or hypercapnia or from medications (such as IV benzodiazepines and narcotics) used to treat their anxiety and pain. Use of an extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant poses new challenges. Unlike mechanical ventilation, which has been considered a contraindication to transplant, ECMO allows patients to remain awake and alert and to participate in physical therapy. However, patients on ECMO are often fearful of their tenuous condition and their total dependence on the machine and the staff. In this setting, they often become demanding and angry and deplete the energy and patience of the ICU team.