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  Increasingly successful solid organ transplantation has increased the need for organ donors.

  
  
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  Maximizing organ procurement and expanding donor acceptance criteria should decrease the organ shortage.

  
  
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  Aggressive ongoing critical care of the multiorgan donor is essential to improve organ retrieval and posttransplant graft performance.

  
  
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  Understanding the process of brain death is essential for directing donor treatment strategies to ensure preservation and function of donor organs.

  
  
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  The goals of management of the multiorgan donor are to maximize organ function by maintaining organ perfusion and oxygenation, and to promptly recognize and treat potential complications such as hypotension, dysrhythmia, pulmonary edema, massive diuresis, coagulopathy, hypothermia, and sepsis.

Organ transplantation has evolved rapidly from the first early successes to the current widespread use of donated organs for the treatment of end-stage kidney, liver, heart, and lung failure.¹ The success of solid organ transplantation has increased the need for an expanded supply of organ donors. In response to this need, the age limit for deceased donors has been increased, and donors over the age of 65 years are frequently successfully utilized.² The use of organs from living-related donors, living-unrelated donors, and non–heart-beating donors (ie, donation after cardiac death [DCD]) has also increased.³ Nevertheless, there has been a progressively widening gap between the number of patients waiting for transplants and the number of transplantations performed. According to the United States Organ Procurement and Transplantation Network (OPTN) as of December 31, 2010, the number of patient registrations was 100,597 with the majority of patients in the 18 to 64 year age range. In 2008, there were 14,203 donors available (deceased = 7984, living = 6219) and a total of 27,961 transplants were performed in the United States.⁴ In cadaveric donors, the largest increase has been in donors older than 50 years of age for last 10 years (170%). One consequence of the increased proportion of older and more diverse donors has been the increase in organs discarded after being procured.³

The relevance of a properly functioning transplanted organ cannot be overemphasized and it is clearly crucial for the success of transplantation of organs requiring immediate function such as the heart and lung. Acute lung allograft dysfunction is the leading cause of death within 30 days of lung transplantation.⁵ Temporary failure of the liver, kidneys, and pancreas may be tolerated with supportive measures such as hemodialysis and pharmacologic interventions.

At a time when transplant surgeons are facing an increasing number of deaths on the waiting list, and as the size of the list continues to grow, there has never been a greater drive to utilize a higher percentage of older or otherwise extended donors, minimize the incidence of primary graft dysfunction, and develop organ donor management strategies that continue to increase the number of organs available for transplant.^6-9

To increase the number of transplantable organs, UNOS created the Critical Pathway for the Organ Donor, a blueprint of an organ donor’s treatment plan. The Critical Pathway is a concise, one-page document designed to help critical care staff and procurement coordinators understand and follow the steps required for effective donor management.¹⁰ After brain death has been declared in potential organ donors and consent is given for donation, donors need to be medically managed to keep their organs viable until organ recovery can occur.¹¹ The Critical Pathway describes optimal care for the organ donor and maps the process to improve the outcome for successful organ transplantation. The Pathway promotes collaboration between organ procurement coordinators and critical care staff, and delineates roles to prevent duplication of effort or confusion.

Studies have shown that the Critical Pathway, which has been endorsed by four major transplantation associations, significantly increased the number of organs procured and transplanted from brain-dead donors.^7,8 There is no sacrifice in the quality of the transplanted organs or an increase in donor management time.

The two major limiting factors in organ donation today are (1) failure to identify patients that are potential organ donors and lack of referral of those patients to the organ procurement organization, and (2) refusal of patients’ families to consent to donation. A proactive donor detection program maintained by well-trained transplant coordinators, the introduction of systematic death audits in hospitals, combined with a positive social atmosphere, appropriate management of mass media relations, and appropriate economic reimbursement for the hospitals are the measures advocated by the Spanish. This model has resulted in the highest continuous increase by far in deceased donor organ donation within a large country, reaching 35 organ donors per million population.¹²

Once a patient is identified as a potential organ donor, the critical pathway should be initiated by contacting the local organ procurement organization to make the referral. Referral is critical; if this does not occur the opportunity for donation may be lost entirely. Organ procurement organization staff may wish to be notified as the condition of the patient deteriorates even before brain death occurs. Most often, the organ procurement organization can quickly do a preliminary assessment to determine whether the patient is a potential candidate for organ donation. If the patient is not a candidate, there is no need to discuss the option of donation with the patient’s family members, and the pathway is stopped. Furthermore, if family members broach the subject of organ donation, a clear answer can be provided as to why the patient is not a candidate for donation, and any confusion can be avoided. Even if a patient is not a candidate for organ donation, the family may have other options to consider, such as donations of eyes, skin, bone, and heart valves.¹³

Referral systems should be automatic and simple. Donors are lost when hospital staff with limited knowledge of the acceptance criteria for organ donors inappropriately rule out potential organ donors as medically unsuitable. Retrospective reviews of the records of patients who have died while in the hospital indicate that a surprising number of potential donors were never evaluated by organ procurement organization staff for this reason. The reasons given for the determination of unsuitability, if any reason is noted in the chart, are many and include age, use of vasoactive drugs, disease (eg, diabetes), cardiopulmonary resuscitation, and positive cultures. Any patient with a significant and potentially life-threatening injury to the head, whether caused by trauma, an intracerebral hemorrhage, or an anoxic event, should be referred to the organ procurement organization as early as possible for evaluation as a potential organ donor. This practice allows the organ procurement organization to evaluate the situation and apprise staff members early on about whether the patient is a potential donor or not. Currently, only a few medical contraindications to donation are absolute, including:

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  Transmissible infectious disease that will adversely affect the recipient (eg, human immunodeficiency virus (HIV) infection, active viral hepatitis B, encephalitis of unknown cause, prion disease, malaria, and disseminated tuberculosis)

  
  
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  Active visceral or hematologic malignant neoplasm

  
  
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  Characteristics that indicate the organ is unlikely to function

Indeed, the only typical feature of a potential donor today is brain death, and with the increased use of non–heart-beating donors in the United States, even brain death is not necessarily typical anymore.

Early referral is also key to success in recovering transplantable organs for potential recipients. If an organ procurement organization receives a referral from the critical care staff well after brain death has occurred, decreases in end-organ function will already have taken place if donors are not appropriately managed. If the organ procurement organization is called in only well after the signs of brain death are present, the donor who might have had 5 to 7 organs suitable for donation and transplantation, may by that time have only 1 or 2 suitable organs. On the other hand, delay of organ procurement to allow optimization of organ condition is also necessary sometimes.^14,15 It has been questioned whether it is reasonable to expect nurses and physicians to keep pace with all of the changes taking place in organ donation, and thus systems have been developed and implemented—sometimes required by law, that do not rely on hospital staff to screen potential donors.¹⁶

The introduction of successful kidney transplantation in the 1950s led to the concept of the use of organs from “heart-beating cadavers.” The clinical findings of “brain death” were first described by French investigators Mollaret and Gaulon in 1959, describing patients on ventilators who have loss of neurologic function after persistent deep coma and loss of spontaneous ventilation; they first called this condition “coma depassé” to denote neurologic damage beyond coma, but they did not equate this entity with death itself.¹⁷ In 1968, the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death was created to standardize the definition of brain death and resolve some of the growing controversies surrounding organ procurement for transplantation from heart-beating donors.¹⁸ The resolutions from this committee are known as the Harvard Criteria of Brain Death. The reasons for this redefinition of death, according to the aforementioned Committee, were the need to bring relief to the families of the sick, free up beds in the intensive care units, and remove the grounds for objecting to the obtaining of organs for transplantation.¹⁹

Two criteria were considered for determining brain death: either the irreversible loss of all of the functions of the entire brain, including the brain stem, or the irreversible loss of the functions of the brain stem only.²⁰

The concept of brain death continues to be a topic of international debate among medical clinicians, anthropologists, philosophers, and ethicists.^21,22 Much of this discussion is the result of the awareness of continuing technological advances, neurodiagnostic developments, and clinical insight. This ongoing dialogue can be viewed as a dynamically developing process of achieving a multidisciplinary consensus that is responsive to a continually changing technological environment.²³

Evidence-based guidelines for determining the brain-death criteria in the United States are based on the Report of the Medical Consultants on the Diagnosis of Death to the President’s Commission on the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research of 1981.²⁴ The President’s Commission requires loss of brain stem function, loss of cortical function, and that the condition is irreversible. Although the guidelines reflect generic, scientifically based recommendations, adaptation of certain details may vary across practice settings and states according to variations in institutional policy and local legislation.²⁵

In 2010, the American Academy of Neurology (AAN) published an updated guideline for determining brain death in adults.²⁶ It provided practical, opinion-based brain death evaluation protocols for clinicians. According to the updated guideline, the 1995 AAN practice parameter for the determination of brain death has not been invalidated by published reports of neurologic recovery in patients who fulfill these criteria. The AAN parameter emphasized the three clinical findings necessary to confirm irreversible cessation of all functions of the entire brain, including the brain stem: coma (with a known cause), absence of brainstem reflexes, and apnea.²⁷

Refusal by the family to provide consent for donation is the most common reason that organs of medically suitable potential donors are not recovered. According to estimates, 35% of the medically suitable organ donors do not donate because the family of the potential donor refuses to consent to donation. Hospitals with low donation rates were more likely to have staff members who perceived dealing with a potential donor as time-consuming and burdensome, and who were uncomfortable with how their hospital handled donation. The role that personal attitudes play in the ability of staff members to handle donation is unclear. Staff members in hospitals with high donation rates have a more positive personal attitude toward donation than do staff members in hospitals with low donation rates; however, a positive personal attitude does not correlate with the ability to approach families about donation.¹⁶

Another situational variable that has a marked influence on donation rates is the timing of the request (ie, when the request is made relative to when the family is informed of the death). Research clearly shows that inappropriate timing of the request (ie, informing the family of the death and requesting donation at the same time) is a formula for family refusal. Families need time to acknowledge the death before they are approached about donation. Consent rates have been shown to increase from 18% to 60% if there was a delay between death and the request for donation. Ensuring that this delay occurs is referred to as “decoupling” of the request. The timing of the request has been evaluated in numerous studies, and all the researchers have reached the same conclusion: that decoupling the request leads to improved donation rates. However, despite vigorous attempts by the organ donation and the health care community to educate critical care staff, about the importance of decoupling the request, a significant number of requests are still “coupled.”^16,28

Unfortunately, current medical school curricula generally lack training on how to break bad news and inform of death. It is important that the word “dead” should be pronounced and not avoided.²⁹ At the brain death declaration, the main task of the intensive care unit staff is not that of obtaining consent for organ removal, but rather counseling and helping the family to cope with the grieving process.³⁰ Minimizing the family’s distress is the focus of care and is an essential prerequisite for a subsequent organ donation request.

Unrestricted visits to the potential donor should not only be permitted, but actively encouraged. All the family’s questions about brain death must be answered unhurriedly by the staff, and the right words should be used in front of a warm cadaver with a heart that is still beating. For example, it is better to use terms which strengthen the certainty of the death, such as “no, he does not breathe, but the ventilator forces the air into the lungs,” or “yes, the heart is still pumping the blood, and it will do so for some hours more because it is artificially stimulated and this is why the skin is warm.” No mention about organ donation should be raised before the concept of brain death is comprehended and the death is accepted by the family. The staff should refer to the dead patient using the past tense; as soon as family members begin to talk of him or her using “was,” the acceptance of death becomes clear. The physician who is in charge of the intensive care unit should only discuss brain death with the family. The discussion relating to organ donation should be introduced by the transplant coordinator so that there is a clear distinction between the two functions (ie, treatment of the patient and preparation for donation). The request should be made by the transplant coordinator in a positive way. It should be proposed as an option that the hospital offers the family for helping other patients, rather than an apologetic or indifferent businesslike gesture. Those who have difficulty in requesting consent should delegate the task to more confident staff. The family must never be forced into making a hasty decision, and it is always advisable to let them take their time and discuss the matter among themselves and with other members of the family before asking again. Often an initial refusal turns into a convinced consent over the course of two or three meetings. While a firm refusal must be respected, hesitation can easily lead to authorization if the subject of the urgent need of organs for many patients, as a lifesaving procedure or a dialysis-relieving therapy, is raised tactfully. The consent process for organ and tissue donation should not only be considered a necessity, but also a family’s right¹⁶ and as a quality measure of an intensive care unit’s performance.

Obtaining consent for organ donation from families is enhanced by:

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  Allowing time for families to accept death

  
  
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  Having someone who is an expert in donation consent approach the family

  
  
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  Approaching the family in a private, quiet area in an unhurried manner

  
  
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  Involving nursing and the organ procurement organization staff in the coordination of the entire consent and donation process

Once consent for organ donation is given, a thorough evaluation is conducted. The organ procurement coordinator collaborates with the critical care nurse to obtain the necessary history and results of diagnostic tests. The donor’s chart is reviewed for prehospital and emergency department entries for details of the events leading to admission. The duration of “downtime” (cardiopulmonary arrest) and cardiopulmonary resuscitation, vital signs, drugs administered, and obvious signs of chest and abdominal trauma are noted. If an old chart or the patient’s primary physician is available, a pertinent medical history is obtained.

Completing a battery of laboratory tests in a timely manner will expedite organ placement and decrease the time required for donor management. A blood sample is also obtained from the donor, to perform bacteriologic and serological screening for infectious disease. This serological sample is usually sent to a central laboratory that performs such testing on a 24-hour basis; however, once the sample arrives at the laboratory, it usually takes about 6 hours for the results to be determined. Usually, the donation coordinator is aware of the serological results as the offers for organ-specific recovery are made.

The organ procurement coordinator reviews a comprehensive medical and social history with the appropriate family members or significant others. Donors are screened for a number of factors, including but not limited to, any history or treatment of heart disease, hypertension, chest pain, or diabetes; use of tobacco, drugs, and alcohol; and high-risk behaviors for transmission of human immunodeficiency and hepatitis viruses.³¹ Pertinent family history is reviewed also. The organ procurement coordinator does a complete physical examination of the donor, paying close attention to any finding that may influence organ integrity. The transplant surgeons determine the suitability of the donor with respect to the transplantable organs.

SCREENING FOR INFECTIOUS AGENTS

Serological screening for HIV, human T lymphotropic virus (HTLV), hepatitis B virus (HBV), hepatitis C virus (HCV), and cytomegalovirus (CMV) is routinely performed along with screening for Treponema antigen (syphilis) and for Toxoplasma.³² The presence of an active viral infection in the form of encephalitis or meningitis, varicella-zoster virus infection, or HIV infection is an absolute contraindication to organ donation because of the hazard that each of these clinical situations pose to the allograft recipient.

Isolated hepatitis B surface antibody positivity usually implies previous vaccination. Hepatitis B surface antigen (HBsAg) positivity reflects the presence of viral DNA in the blood that is related to current hepatitis B infection or a remote infection that has not cleared. These donors have contagious hepatitis B and will transmit the disease to the recipients unless the recipient has neutralizing antibodies due to previous exposure or vaccination.³² Patients who have acute hepatitis infection develop antibodies to the core antigen early in the course of the disease. Donors who are core antibody–positive should be considered infectious because they may be convalescing from acute infection. If both surface and core antibodies are positive, the patient has recovered from hepatitis B and demonstrates immunity. Nevertheless, liver recipients from these donors are at significant risk for the development of acute hepatitis B infection, as opposed to the recipients of the other organs. Organs from these core-positive donors are generally reserved for patients with a documented response to the hepatitis B vaccine.^32,33

All hepatitis C antibody–positive donors should be considered infectious.³² The hazard of HCV transmission from a previously infected organ donor is a concern for all allograft recipients. Approximately 5% of all organ donors are positive for antibody to HCV. The presence of antibody to HCV is indicative of HCV infection, because antibody to HCV appears in peripheral blood within 2 months of HCV exposure. Most organ procurement organizations have adopted a policy of screening organ donors for antibody to HCV. IgG antibody to HCV does not protect against donor organ contamination; however, the risks of transmission from HCV-RNA negative, HCV antibody-positive donors have not yet been fully determined.³²

Although a positive screening result does not necessarily rule out organ donation, a selective strategy of reserving organs from HCV-positive donors for recipients with previous HCV exposure and detectable antibody to HCV can be applied. Transplantation of a liver or kidney(s) from a donor positive for antibody to HCV to a recipient positive for antibody to HCV did not appear to cause increased 1- or 5-year mortality.³⁴ But a more recent report with a large cohort (>36,000 cases) has shown that kidney transplantation from HCV-donors does increase posttransplant mortality even in the subgroup of HCV-seropositive recipients.³⁵ Transplantation of an HCV-positive lung or heart-lung allograft when a HCV-negative recipient’s life is in danger may be the only alternative to immediate death because an HCV antibody–positive donor is an independent poor prognostic indicator for 1- and 5-year survivals.^34,36 Table 116-1 shows the relative risk of viral transmission for hepatitis B and C viruses.

Transplantation of an organ from a CMV-positive donor can result in subsequent reactivation of latent virus and replication in the immunosuppressed host.³⁷ The specific CMV serological status of the donor and recipient has implications for prophylaxis, the highest-risk group being CMV-seronegative recipients of CMV-seropositive donor organs (ie, the so-called primary mismatch group).

Nevertheless, transplantation of organs from CMV-seropositive donors has not been considered an absolute contraindication for transplantation, because the high sero-prevalence of the virus among the general population makes it impractical to rule out such donors. Regardless of donor CMV status, seronegative recipients should receive prophylaxis longer than CMV-seropositive recipients to prevent CMV disease after transplant.³²

Serological screening of organ donors for EBV is commonly performed because primary EBV infection (ie, transplantation of an organ from an EBV-seropositive donor to an EBV-seronegative recipient) is associated with an increased risk of posttransplant lymphoproliferative disease (PTLD).³⁸ Therefore, recognition of this mismatch in a potential allograft recipient known to be EBV-negative is important prognostic information.

The detection of antibody to treponemal antigen is not a contraindication to organ procurement, but it is a contraindication to tissue procurement. A standard course of penicillin therapy would provide sufficient antibiotic coverage to prevent syphilitic complications in an allograft recipient.³² The possible transmission of the protozoan Toxoplasma gondii is a concern, especially for heart allograft recipients, because of the predilection of this parasite for muscle tissue. Organ procurement from seropositive donors is not contraindicated; however, the detection of seropositivity means that the recipient may be placed at high risk. Fortunately, the use of trimethoprim-sulfamethoxazole as prophylaxis for Pneumocystis carinii infection prevents transmission of T gondii.³⁹

Regional directives will need to be implemented as necessary with regard to novel infectious agents carrying alarming epidemic/pandemic life-threatening potential.⁴⁰ Regions of North America have been faced with a relatively new entity, West Nile virus⁴⁰ and more recently, H1N1 influenza virus infection.⁴¹ Organ donors should be tested for evidence of West Nile virus viremia by polymerase chain reaction (PCR), nucleic acid amplification,⁴²

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