Anesthesia for Organ Procurement


Key Points

  • The shortage of organs available for transplantation is a worldwide problem.

  • The discrepancy between the number of patients waiting for organ transplantation and the available organs remains significant, but has narrowed since 2013.

  • Most organs in the United States are donated after neurologic death, with a small portion donated after circulatory death and from living organ donors.

  • Neurologic-death donors have physiologic alterations that must be actively managed to ensure that the organs are suitable for transplantation.

  • Determining neurologic death and circulatory death should follow national guidelines and local institutional protocols.

  • The anesthesiologist must have an awareness of the ethical and legal issues related to the declaration of death that precedes organ donation.

  • Expansion of the donor pool through the inclusion of extended criteria, such as high-risk donors, addresses the organ shortage and decreases waiting-list mortality.

  • The use of extended criteria high-risk organs significantly impacts recipient outcomes and presents challenges to perioperative management.

  • Ischemia-reperfusion injury in organ transplantation is unavoidable; however, management strategies can lessen the likelihood of postoperative graft failure.

  • Goal-directed donor management can improve the number of organs transplanted per donor.

  • Living organ donor kidney transplantation remains an important donor source in the United States, whereas the use of living donors for liver transplantation varies by country.

  • New technologies, including machine perfusion after procurement, are promising as a means to mitigate the effects of prolonged preservation time, to increase the donor pool, and to improve transplant recipient outcomes.

Introduction

Organ transplantation requires the donation and successful procurement of a human organ. The success of organ transplantation relies on a functioning donor graft. The majority of organs used for transplantation in the United States are from donors after the declaration of neurologic death (donation after neurologic death, DND). Organs from donation after circulatory (cardiac) death (DCD) and living organ donation are in the minority, however, they remain an important source of donors. Organs procured from these sources have different characteristics and present varying challenges in management. For instance, DND donors often have significant physiologic alterations and hemodynamic instability that is associated with neurologic death. These alterations and instability, if not treated, will lead to organ deterioration and may prevent the organ from being suitable for transplantation. In contrast, DCD donors have an obligatory period of hypotension of varying duration before cardiac arrest. The resulting compromise in perfusion can exacerbate reperfusion injury and lead to an increased incidence of posttransplant biliary dysfunction.

The shortage of organs is a worldwide problem and is the most important obstacle in organ transplantation. The gap between the number of patients waiting for transplant and the available organs has widened ( Fig. 61.1 ). In 2015, more than 119,000 transplant candidates were wait-listed in the United States through the United Network for Organ Sharing. Of these, 33,000 candidates underwent transplant surgery. The majority of candidates were awaiting kidney grafts, with a smaller number awaiting liver, heart, and lung grafts. Many strategies were implemented to decrease the gap between the demand and supply, including public awareness campaigns and updates to the organ allocation system. Organ donation rates and the number of organs transplanted per donor vary substantially across geographic regions. Per 100 eligible deaths in the United States in 2016, the organ donation rate was 72.3, ranging from 52.9 to a high of 93.3 (Israni OPTN 2016 Annual Data Report). To increase the number of organs for transplant, many programs have expanded the donor pool by using extended criteria donors (ECDs). Not surprisingly, the number of organs transplanted per donor varies according to donor category: ECD, DCD, or standard criteria donor (SCD). The number of organs transplanted from DCD donors is similar to ECDs, primarily attributable to the ability of the kidney to tolerate the longer periods of ischemia associated with organ procurement after DCD. The use of living-related and living-unrelated donors is widespread in countries with moral or legal objections to neurologic death and is an important worldwide donor source. Many policies have been proposed to promote the best practices in organ donation. There are several areas that have the potential to expand the donor pool, which include deaths that are not referred to the organ sharing agencies and organs that have been procured, but unused for transplant.

Fig. 61.1, The gap in the United States between the number of donors, patients transplanted, and patients on the waitlist by year, 1991 to 2015. The gap has declined since 2013.

Organ transplantation is a complex process that requires close coordination among many specialized teams. Procurement organizations, transplant coordinators, social workers, nurses, surgeons, internists, intensivists, and anesthesiologists are involved in the process. To maximize the number of organs transplanted and to preserve the best possible function of donated organs, anesthesiologists need to understand the pathophysiologic derangements associated with donation and ischemia-reperfusion injury. In addition, anesthesiologists must be aware of the ethical and legal issues related to the declaration of death and organ donation.

Management of Organ Donors After Declaration of Neurologic Death

DND (also called after declaration of brain death) provides the majority of donated organs in the United States. Organ procurement from DND donors can only occur after the declaration of death. The concept of neurologic death emerged in the 1950s. In 1968, a Harvard Ad Hoc Committee on Irreversible Coma established a set of criteria that has been widely used for the determination of neurologic death. In the United States, the Uniform Determination of Death Act was approved in 1981 by the National Conference of Commissioners on Uniform State Laws, in cooperation with the American Medical Association, the American Bar Association, and the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. Although the criteria for the declaration of neurologic death were based on ethical principles established several decades ago, the criteria remain valid today.

Although the concept of neurologic death has been widely accepted in Western cultures, minor variations in definition and implementation exist in different countries. Despite these differences, the clinical criteria are similar. A larger difference exists among different cultures in accepting and implementing the neurologic death criteria. In fact, neurologic death has not reached a legal status in some countries, such as China.

Pathophysiologic Changes With Neurologic Death

A variety of pathophysiologic changes are associated with neurologic death. The pathophysiologic mechanisms of neurologic death have profound effects at the molecular, cellular, and tissue levels. The clinical presentations associated with neurologic death may be complex and vary from patient to patient. They can be further complicated by prior pathologic abnormalities, disease, and therapy. The typical pathophysiologic changes associated with neurologic death are further described in Table 61.1 .

Table 61.1
Pathophysiologic Changes Associated With Neurologic Death
Signs and Symptoms Pathophysiologic Changes Incidence (%)
Hypertension Catecholamine storm 80-90
Hypotension Vasoplegia, hypovolemia, reduced coronary blood flow, myocardial dysfunction 80-90
Bradycardia and other arrhythmias Catecholamine storm, myocardial damage, reduced coronary blood flow 25-30
Pulmonary edema Acute blood volume diversion, capillary damage 10-20
Diabetes insipidus Posterior pituitary damage 45-80
Disseminated intravascular coagulation Tissue factor release, coagulopathy 30-55
Hypothermia Hypothalamic damage, reduced metabolic rate, vasodilation, and heat loss Varied
Hyperglycemia Decreased insulin concentration, increased insulin resistance Common

Cardiovascular Responses to Neurologic Death

The cardiovascular system is closely regulated by the central neural system. Cardiovascular responses to neurologic death usually consist of two phases. The first phase is characterized by sympathetic discharge (catecholamine storm), which causes intense vasoconstriction or elevated systemic vascular resistance (hypertensive crisis), tachycardia, and a redistribution of blood volume with visceral ischemia. Acute myocardial injury can occur in neurologic-dead donors without a history of coronary artery disease. Echocardiographic evidence of myocardial dysfunction is observed in 40% of neurologic-dead donors under consideration for heart donation. At times, parasympathetic activation can result in bradycardia. After the sympathetic discharge of the first phase, the loss of sympathetic tone, decreased cardiac output, blunted hemostatic responses, and severe peripheral vasodilatation (vasoplegia) characterize the second phase. In addition to neurohormonal disturbances, other contributing factors include blood loss, intravascular depletion attributable to capillary leakage, osmotic therapy for rising intracranial pressure (ICP), and diabetes insipidus.

The first phase is correlated with ischemia in various parts of the brain and is attributable to an increase of ICP, and the second phase is caused by cerebral herniation and spinal cord ischemia. Although the first hypertensive phase generally represents a transient period in the progression to neurologic death, the second hypotensive phase is profound and sustained. Failure to correct these cardiovascular derangements results in poor organ perfusion and inadequate tissue oxygenation, which will threaten the viability of the donated organs.

Respiratory Responses to Neurologic Death

An increase in systemic vascular resistance after neurologic death results in blood shifting from the systemic circulation to the more compliant pulmonary circulation. The resulting increase in hydrostatic pressure in the pulmonary circulation causes pulmonary capillary leakage and pulmonary edema. Sympathetic activity triggers a sterile systemic inflammatory response, initiating infiltration of neutrophils and increasing pulmonary endothelial permeability, which further contributes to lung injury. Proinflammatory cytokines are released at the alveoli and are associated with early graft failure and mortality after lung transplantation. The inflammatory response in neurologic-dead donors is associated with the deterioration in cardiac function and a shift to anaerobic metabolism. Hormonal instability can reduce alveolar fluid clearance, resulting in significant accumulation of extravascular lung water. If ventilation is not supported, then respiratory arrhythmia progresses to apnea and cardiac arrest.

Endocrine, Metabolic, and Stress Responses to Neurologic Death

Neurologic death is frequently associated with pituitary failure and disturbances of cortisol, thyroid hormones, antidiuretic hormone, and insulin. Posterior pituitary function in neurologic-dead donors is frequently lost. The development of central diabetes insipidus results in severe fluid and electrolyte derangements and can be observed in up to 90% of neurologic-dead donors. Anterior pituitary function in neurologic death can also be affected, resulting in a deficiency in triiodothyronine (T 3 ) and thyroxine (T 4 ), adrenocorticotropic hormone, thyroid-stimulating hormone, and human growth hormone. Thyroid hormonal deficiency may be similar to the euthyroid sick syndrome commonly observed in the non-neurologic injured patient with multisystem organ failure. Hyperglycemia is commonly encountered in neurologic-dead donors because of decreased insulin concentrations and increased insulin resistance. Hypothalamic function and control of body temperature are lost. Although hyperpyrexia may initially occur, hypothermia follows, which is caused by a reduction in metabolic rate and muscle activity, in combination with peripheral vasodilation. Disseminated intravascular coagulation is present in up to one-third of isolated patients with head injuries and is believed to be caused by the release of tissue thromboplastin from brain tissue.

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