Organ transplantation is the removal of an organ from one person (the donor), and placement into another (the recipient). Transplantation is performed in patients with end-stage organ failure and can increase life expectancy while also improving the patient's quality of life. The most commonly transplanted solid organ is the kidney, followed by the liver, heart, and lungs. Pancreatic and intestinal transplants are performed as well but are less common. More recently, vascularized composite allografts (VCAs, e.g., face, hand, penis) have been performed for reconstructive procedures.[1][2] Non-vital tissues, such as bones, corneas, and tendons, may also be transplanted. Organ donations can arise from living or deceased donors, but deceased donors are more common.

Deceased patients are the major contributor to donor organs, and the most common causes of death are cerebrovascular accidents followed closely by traumatic brain injuries. In recent years, opioid overdoses have become another significant source of deceased organ donation.[3][4] The dead donor rule holds that patients must be declared dead before the harvesting of donor organs. Donations can arise from patients who have suffered brain death or circulatory death. Brain death is a clinical diagnosis, defined as the permanent loss of brain function. This condition requires an irreversible loss of consciousness, absence of brain stem reflexes, and a lack of spontaneous respiration.[5][6][7] The diagnosis of brain death must be made before organ harvesting occurs. The definition of circulatory death is the irreversible loss of cardiopulmonary function.[8][9] Donation after circulatory death has been increasing in attempts to address the demand/supply mismatch of donor organs worldwide.[10] This process involves the withdrawal of life-sustaining treatment, followed by a declaration of death after permanent cessation of circulation. To avoid any conflicts of interest, the decision to withdraw care must take place before any discussion of organ donation, and members of the organ procurement/transplant teams should not be involved in the process of care withdrawal or the declaration of death.[11]

Living donations are less common but still serve to increase the existing donor pool. Over 7300 living donations were performed in the United States in 2019, saving patients from a potentially long-wait on the transplant list. The most frequently donated organ is a kidney, but portions of the liver or lung are transplanted as well. More recently, living donations of VCAs have been explored.[12] There are three types of living donations, the most common being directed donation. In directed donations, the donor designates to whom their organ will be given - most frequently a family member or close social acquaintance. In non-directed donation, also-known-as altruistic donation, the donor does not specify a recipient, and the organ is matched to a patient in need. Paired donations are more complicated, but generally involved two (or more) patients with a willing donor who is not a match for them. The pairs are then grouped, and the organs are 'traded' to ensure that all patients receive a compatible transplant. Living donations are considered safe, as donation has shown limited harmful outcomes, but patients must be closely followed to assess for medical and psychological harm.[13][14] Long-term studies have suggested no adverse psychological outcomes with a living donation, and high levels of overall life satisfaction, both for directed and non-directed donation.[15][16] Non-donors - potential donors who were unable to donate due to a negative match or withdrawal from consideration - were found to have lower levels of life satisfaction than living donors.[17]

The number of patients awaiting organ transplantation far outstrips the availability of donor organs. In the United States, estimates are that a new patient is added to the transplant list every ten minutes, and twenty patients die every day while awaiting transplant. In 2019, surgeons performed nearly 40,000 transplants, but at the end of the year, over 110,000 patients remained on the waiting list. While there are multiple ways to consent to organ donation (including a signed donor designation, designation on a driver's license, or signed consent from the deceased's next-of-kin), the estimate is that only 30 to 40% of potential donors in the United States become actual organ donors.[18] Approximately 80% of Americans support organ donation, but only 40% have an appropriate designation in place to donate their organs after death. This disconnect can be attributed, in part, to how the question of donation is presented.[19] The United States operates under an opt-in system, where the default is not to be an organ donor, and an active action is necessary to become an organ donor. In an alternative strategy, the presumed consent system, citizens are designated as organ donors unless they elect to opt-out. This strategy, commonly used in retirement savings, has shown mixed results in practice, with increased organ donation in countries with very low rates, but no significant increase in others.[20][21] Critics of this strategy argue that the policy is unethical, as failing to object is not equivalent to informed consent.[22] Others have shown that increasing the pool of potential donors will not increase the number of transplants performed if the proper infrastructure is not in place.[23]

The Function of Transplantation in Trauma Patients

Patients who have suffered traumatic injuries should be evaluated and resuscitated according to Advanced Trauma Life Support (ATLS) protocol, developed by the American College of Surgeons (ACS), including a proper primary and secondary survey.[24][25] The physician's primary focus must be the well-being of the patient during active resuscitation.[26] However, the recognition of potential organ donors can increase donor organ availability and viability. The ACS requires all verified trauma centers to establish a relationship with an Organ Procurement Organization (OPO) and to notify the OPO when a potential organ donor is available. Local OPOs assist with the coordination of organ donation, including the evaluation of potential donors, obtaining consent for organ donation, organ allocation, and the procurement process. Contacting the local OPO is the first step in 'The Critical Pathway,' a systematic approach to deceased organ donation. The critical pathway consists of five total phases, which can overlap.[27]

• Phase I - Identification of Potential Organ Donors, Referral to OPO
• Phase II - Declaration of Death, Acquisition of Consent for Organ Donation
• Phase III - Donor Evaluation
• Phase IV - Donor Management
• Phase V - Organ Procurement

Trauma donors are generally younger and have fewer co-morbidities than non-trauma donors. On average, trauma donors are more likely to yield additional (non-kidney) organs and produce more organs per donor, overall.[28] Higher rates of organ donation were found in patients who suffered traumatic brain injury versus traumatic cardiac arrest, and in pediatric versus adult patients.[29] Cardiac arrest/dysfunction is associated with lower donation rates, likely secondary to poor organ perfusion.[30]

Medical ethics, a set of values used to navigate complicated situations, are founded in the concepts of patient autonomy, beneficence, non-maleficence, and justice.[31] All four of these concepts are relevant in organ transplantation, and certain instances can conflict with one another.[32] Much of the ethical framework surrounding organ transplantation has its basis in the dead donor rule, which states that a patient must be declared dead before permitting the removal of vital organs. The dead donor rule is particularly relevant in donations after circulatory death, where the patient's circulatory function must irreversibly cease before beginning organ procurement. While most donations after circulatory death arise from neurologic injuries, it has also been used for end-stage pulmonary and neuromuscular disorders. Currently, after withdrawing life-sustaining care, providers await the cessation of cardiopulmonary functioning to declare death. Following this, clinicians observe a 'hands-off' period (typically 5 minutes) to ensure that no auto-resuscitation occurs. If no declaration is possible within a pre-designated period (usually 60 minutes), it cancels the donation. Some have questioned the utility of this approach in patients electing to withdraw care and a desire to donate their vital organs. In these patients, waiting for death can lead to ischemia, reducing the quality of donor organs or non-donation. 

In 2016, Canada introduced Medical Assistance in Dying (MAID), for cases of grievous and irremediable suffering. With an estimated 2,000 cases of euthanasia per year, this may present another avenue for increasing organ availability. From 2016 to 2019, 30 patients made donations for a total of 74 organs donated.[33] Voluntary euthanasia differs from the traditional withdrawal of care in two key respects - euthanasia requires first-person consent, and the primary intent is to end life. Withdrawal of care intends to provide comfort to the patient, with death as a side effect (the principle of the double effect).[34] Rethinking the dead donor rule could allow these patients to donate their organs prior to death, fulfilling their wishes.[35] Advocates of this approach argue that withdrawal of care with a do-not-resuscitate order in place is equivalent to death, and awaiting 'irreversibility' does more harm than good.[36] Opponents to this approach argue that it violates the principle of non-maleficence and public trust, and a loss of public trust will lead to a decrease in organ availability. However, a 2015 study suggested that approximately 70% of Americans would support organ donation before death.[37]

Donation after Brain Death (DBD)

The definition of brain death is the irreversible loss of consciousness, absence of brainstem reflexes, and persistent apnea. It is a clinical diagnosis made by two independent physicians. The most common causes are cerebrovascular accidents and traumatic brain injuries, but can also occur secondary to anoxia or brain tumors. To make a diagnosis of brain death, the patient must be in an irreversible coma with a known cause and completely unresponsive to mechanical stimuli. All reversible causes of coma must be excluded. The patient must be weaned off CNS depressant medications (alcohol, opioids, anesthetics) and neuromuscular-blocking agents. The patient cannot be hypothermic (core body temperature <35 degree Celsius) or hypotensive (mean arterial pressure [MAP] <60 mmHg). Severe acid-base and electrolyte abnormalities must be ruled out as well. All brainstem reflexes should be assessed, including the pupillary, corneal, oculocephalic, vestibular, and cough/gag reflexes. Spinal reflexes remain in up to 75% of patients, and their presence does not preclude a diagnosis of brain death. The apnea test can assess ventilatory drive. The patient is disconnected from the ventilator for 10 minutes, and a positive test occurs with absent respiratory effort and increasing PaCO2. The apnea test should stop, and the patient reconnected to the ventilator if the patient experiences hypotension, hypoxemia, or cardiac arrhythmia. A false-positive apnea test can occur when the patient is sedated or with a high cervical injury impairing diaphragmatic function. While brain death is a clinical diagnosis, additional testing can support the diagnosis, particularly when confounding factors are present. Electroencephalography (EEG) is a common method to assess for brain electrical activity, as it is non-invasive and is performable at the bedside. However, it can be heavily influenced by sedation, hypothermia, and metabolic derangements, limiting its usefulness. Cerebral angiography, transcranial doppler ultrasound, and cerebral scintigraphy - all assessments of cerebral blood flow - are not influenced by CNS depression, hypothermia, and metabolic disorders, making them very useful as confirmatory tests for brain death.[38][39]

Donation after Circulatory Death (DCD)

Circulatory death, defined as the permanent absence of respiration and circulation, is becoming increasingly prevalent in attempts to expand the number of potential organ donors. The typical DCD patient is one who has suffered a neurologic injury but does not fit the criteria for brain death; less common are patients with respiratory or neurodegenerative disease who are planning to withdraw treatment electively. Initially, only kidneys were transplanted, but the practice has expanded to include liver, lung, and pancreatic transplants. One of the primary challenges of DCD is the balance of ensuring donor death, while also limiting ischemia to the desired organs.  The Maastricht classification system is used to classify these patients into five categories based on the type of circulatory death, location, and other factors. There are two defined forms of DCD - controlled circulatory death, and uncontrolled circulatory death.[40][41] Uncontrolled DCD is most frequently seen when a patient is dead-on-arrival to the Emergency Department or undergoes insufficient resuscitation after arrival. Unexpected cardiac arrests in the ICU also classify as uncontrolled. Due to their unexpected nature, organ donations in this group are more complicated. End-organ ischemia has likely already begun, and steps are necessary to halt this progression while obtaining consent and preparing for organ procurement. Often, uncontrolled DCD is limited to a kidney-only donation, or possibly no donation, as a result of ischemic injury. In contrast, controlled DCD occurs when a patient undergoes an anticipated cardiac arrest. In these cases, the decision to withdraw care must take place before the decision to donate, and the declaration of death often occurs in the operating room. Life-sustaining care is withdrawn, and the patient is monitored until there is a loss of cardiopulmonary function. Following a waiting period (often 5 minutes, to ensure no spontaneous resumption of cardiac function), the patient can be declared dead, and procurement can begin. In approximately 20% of cases, the donor is not declared dead within a pre-determined period (commonly 60 minutes), and organ procurement is aborted. Members of the procurement team are not involved in the process of care withdrawal or declaration of death, and should not enter the operating room until death is declared.[42] While DCD organs are at higher risk for ischemia, research shows comparable outcomes between DBD and DCD organs in kidney, liver, lung, and pancreatic transplantation.[43][44][45][46]

Organ Procurement

Following the death declaration and appropriate preparation, the process of organ retrieval may then commence in the operating room. The patient is prepped and draped in a sterile fashion, and the intended organs mobilized. The donor is then exsanguinated, and blood rapidly replaced with a preservation solution. These solutions are hypothermic (often 5 to 10 degrees Celsius) and function to rapidly lower the temperature of the intended organs - decreasing metabolism and facilitating preservation. Rapid cooling can be enhanced with topical ice. Following cooling, the intended organs are removed, placed in sterile containers on ice, and then transported to another location for implantation. In general, the heart/lungs are removed first, followed by the liver then the kidneys. During organ removal, vascular conduits are an option to assist with vascular reconstruction during implantation. After solid organ removal, other tissues (bones, corneas, tendons, etc.) may be removed.