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 testingon 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. 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.8–10
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.
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. 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, then 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.15
All hepatitis C antibody-positive donors should be considered infectious. 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, it is also important to emphasize that detection of antibody to HCV by serological screening of the donor is not predictive of HCV transmission.
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 from a donor positive for antibody to HCV to a recipient positive for antibody to HCV does not appear to cause increased morbidity or mortality. Transplantation of an HCV-positive heart or lung allograft when a HCV-negative recipient's life is in danger may be the only alternative to immediate death.16,17 Kidney recipients who are hepatitis C positive can shorten their time on the waiting list by accepting a kidney from a HCV-positive donor. Table 91-1 shows the relative risk of viral transmission for hepatitis B and C viruses.17
Table 91–1. Risk of Hepatitis Viral Transmission ||Download (.pdf)
Table 91–1. Risk of Hepatitis Viral Transmission
|Donor serology||HBsAb+ recipient||HBsAb−recipient|
|HBsAg+||Liver: Insufficient data||Liver: High|
|Non-liver: Insufficient data||Non-liver: High|
|HBcAb+||Liver: Low – Moderatea||Liver: Moderate to High|
|Non-liver: Very low||Non-liver: low|
|Liver: Highb||Liver: High|
|Non-liver: Insufficient datac||Non-liver: High|
Transplantation of an organ from a CMV-positive donor can result in subsequent reactivation of latent virus and replication in the immunosuppressed host. 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 (i.e., the so-called primary infection group).
Nevertheless, transplantation of organs from CMV seropositive donors has not been considered an absolute contraindication for transplantation, because the high seroprevalence of the virus among the general population makes it impractical to rule out such donors. Furthermore, recent evidence suggests that even mismatches between CMV-positive donors and CMV-negative recipients can be successfully overcome by strategies aimed at prophylaxis for CMV infection.
Over 95% of potential adult donors are seropositive (IgG antibody) for Epstein-Barr virus (EBV); thus serological screening of organ donors for EBV is not routinely performed. However, primary EBV infection (i.e., transplantation of an organ from an EBV-seropositive donor to an EBV-seronegative recipient) is associated with an increased risk of posttransplant lymphoproliferative disease. Therefore, recognition of this mismatch in a potential allograft recipient known to be EBV-negative may be important prognostic information. Currently, there is no effective means of preventing this complication.
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.
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.16
Regional directives will need to be implemented as necessary with regard to novel infectious agents carrying alarming epidemic/pandemic life-threatening potential. Recently regions of North America have been faced with two relatively new entities, West Nile virus and the severe acute respiratory syndrome (SARS). Organ donors should be tested for evidence of both West Nile virus viremia by polymerase chain reaction (PCR) and early antibody response (IgM) to West Nile virus. If either test is positive the potential donor is to be deemed ineligible for organ donation.
SARS screening is currently conducted by using a specifically directed series of questions on the donor medical and social history questionnaire. This investigates the donor institution's category of contamination as determined by the infection control officer at that institution; the donor's clinical history relative to the last 10 days prior to donor assessment with regard to signs or symptoms associated with SARS; and epidemiologic links related to direct contact with SARS risk or travel to an area listed in the current Travel Health Advisory.18
Transmission of donor malignancies is rare, with 18 cases from 34,933 cadaver donors and 3 cases from 32,052 living donors being reported to UNOS from 1994 through 2001. Donors with past histories of certain types of cancers may be considered as donors, including certain types of primary central nervous system (CNS) tumors. Risks of cancer transmission from donors with a history of nonmelanoma skin cancer and selected cancers of the CNS appear to be small. When considering organ use from donors suffering from intracranial malignancies, there are a number of general guidelines. Most important is to consider the known biologic behavior of various CNS neoplasms and their propensity to spread outside of the cranial vault. Repeated craniotomies as well as ventriculoperitoneal or ventriculojugular shunts have been associated with increased risk of metastasis.17,19–21
Risks of tumor transmission with certain other types of cancer may be acceptable, particularly if the donor has a long cancer-free interval prior to organ procurement, while certain other cancers pose a high transmission risk. Tumors that pose a high transmission risk include choriocarcinoma, melanoma, lymphoma, and carcinoma of the lung, colon, breast, kidney, and thyroid.
A list has been developed outlining the relative risks of CNS tumor transmission from cadaver donor to allograft recipient (Table 91-2).
Table 91–2. Relative Risk of Central Nervous System Tumor Transmission ||Download (.pdf)
Table 91–2. Relative Risk of Central Nervous System Tumor Transmission
- Lowest risk
- Benign meningiomas
- Pituitary adenomas
- Acoustic schwannomas
- Astrocytoma (grade I)
- Epidermoid cysts, colloid cysts
- Low-grade oligodendromas
- Gangliogliomas, gangliocytomas
- Pineocytomas, ependymomas
- Well-differentiated teratomas
- Moderate risk
- Astrocytoma (grade II)
- Gliomatosis cerebri
- Highest risk
- Anaplastic astrocytoma (grade III)
- Glioblastoma multiforme
- Anaplastic oligodendroglioma
- Malignant ependymomas
- Primary cerebral lymphomas
An initial electrocardiogram (ECG) should be obtained on every potential cardiac donor, and additional ECGs should be obtained when changes in heart rhythm occur. ECG changes may be temporary and related to alterations in sympathetic output. Nonspecific ST-segment and T-wave changes, prolonged QT intervals, and T-wave inversion are common. Tachycardia is common and may be caused by diabetes insipidus, diuresis, hemorrhage, vasopressor therapy, or electrolyte disturbances. ECGs are evaluated for signs of acute myocardial injury.8
A transthoracic or transesophageal echocardiogram may be obtained to evaluate motion of the heart wall and valve function, estimate ejection fraction, and to detect a pericardial effusion. Transient changes that do not preclude heart donation include a stunned myocardium or myocardial depression related to acidosis and hypoxemia. If the causes of the changes are reversible, the heart may still be successfully transplanted. Although echocardiography is effective in screening for anatomic abnormalities of the heart, the use of a single echocardiogram to determine the physiologic suitability of a donor is not supported by clinical evidence. An alternative approach, using a pulmonary artery catheter to guide the physiologic assessment and management of ventricular dysfunction, has been used with success in the United Kingdom.
Assessment and management of donor left ventricular dysfunction offers the greatest potential to increase heart donor utilization. Strong evidence indicates that younger hearts with left ventricular dysfunction can recover normal function over time in the donor and after transplantation into a recipient. Metabolic abnormalities, anemia, and excessive doses of inotropes should be corrected prior to obtaining an echocardiogram. Aggressive donor management, including pulmonary artery catheterization and hormonal resuscitation, should be performed in donors with an initial left ventricular ejection fraction less than 45%. Table 91-3 shows the heart donor criteria recently modified to potentially expand the available pool of cardiac donors.17
Table 91–3. Heart Donor Criteria ||Download (.pdf)
Table 91–3. Heart Donor Criteria
|Age||Donors >55 may be used selectively, though coexisting LVH and longer ischemic times may increase recipient mortality risks|
|Size||Despite an increased risk associated with small donors, a normal-sized adult male (>70 kg) donor is suitable for most recipients|
|LVH||Mild LVH (wall thickness <13 mm by echocardiography and no LVH by ECG criteria) does not preclude recovery, particularly with shorter ischemic times|
|Valvular lesions||Certain lesions, such as mild or moderate mitral or tricuspid regurgitation, or a normally functioning bicuspid aortic valve may be amenable to repair prior to transplantation|
|Congenital lesions||Certain lesions, such as a secundum type ASD, may be amenable to repair|
|Coronary angiography||a. Male donor age 35–45 years and female donor age 35–50 years: perform angiography if there is a history of cocaine use or ≥3 risk factors for CAD|
|b. Male donor age 46–55 years and female donor age 51–55 years: angiography recommended|
|c. Age >55 years: angiography strongly recommended|
|CAD||Donor hears with mild coronary artery disease should be considered for recipients with relatively urgent need|
The suitability of donor lungs for transplantation is determined with several diagnostic tests. A chest radiograph should be interpreted by a radiologist or qualified physician. A complete history of the donor's treatment while in the hospital, including the use of vasopressors and results of arterial blood gas analyses, are shared with centers considering the transplantation of lungs. Smoking history should be reported, along with the results of Gram stains of sputum (a specimen for detection of yeasts and fungi is desirable), and a description of the sputum characteristics. In addition, a bronchoscopic examination is performed to assess for signs of aspiration, and to document evidence of a foreign body or presence of blood or other material entering the lower airways from above. It also allows assessment of the character and amount of secretions in the lung and provides microbiologic specimens. A bronchoscopic examination will also promote pulmonary stability in the donor by removing airway secretions that may have accumulated. Blood gases are repeated every 3 hours to assess the results of interventions and to determine trends. Repeat pulmonary recruitment maneuvers are performed to optimize ventilation-perfusion matching.
Wider application of broader criteria for donor selection and procurement is possible and can clearly increase the size of the donor pool. If uniform multidisciplinary donor management protocols were developed, increased lung utilization would follow. Table 91-4 shows the current criteria that are used to determine the suitability of a cadaver lung donor. The Lung Transplant Working Group proposed the new criteria to include virtually any donor up to the age of 65 years, in the absence of significant lung injury from smoking, and absence of cancer with metastatic potential.8,17,22,23
Table 91–4. Lung Donor Criteria ||Download (.pdf)
Table 91–4. Lung Donor Criteria
- PO2:FiO2 ratio >300, FiO2 = 1.0, PEEP = 5 cm H2O
- Clear chest x-ray
- Age <55 years
- Absence of major chest trauma
- Absent aspiration, sepsis, or purulent secretions
- Smoking history of <20 pack-years
- No history of malignancy
In an effort to augment the donor pool, criteria have been loosened with the retrieval of organs from donors with greater smoking histories, infiltrates on radiography, or marginal gas exchange. Because these previously-considered marginal donors, or more appropriately termed “extended” donors, are now being used any potential brain-dead patient without obvious contraindication to cadaveric donation should be referred to appropriate local organ procurement agencies for final determination of suitability.17,23
The discard rate of kidneys procured from cadaveric donors in the U.S. has been increasing to an alarming level of more than 15% of those kidneys recovered for transplantation. Approximately 50% of kidneys from cadaveric donors over 60 years of age (older-age donors) are not transplanted due to donor quality.
The renal system in a cadaveric donor undergoes a number of physiologic changes that are influenced dramatically by both the medical therapies used to prevent brain death and by brain death itself. The results of basic renal function tests such as measurement of serum levels of creatinine and urea nitrogen and urinalysis should be reviewed to provide a profile of renal system function in the donor since admission. When kidney donors are evaluated, the effect of hemoconcentration on the results of these studies should always be considered. Elevated levels of serum creatinine and urea nitrogen and atypical urinalysis findings may suggest that renal function was compromised. The relative risk of dialysis after transplantation is 1.5 times greater in recipients of kidneys from donors >55 years of age vs. those who are <55. Table 91-517 shows the latest approved expanded kidney donor criteria, based on the relative risk >1.7 of having a graft failure for donors older than 50 years of age with at least two of the following factors: creatinine >1.5 mg/dL, a cerebrovascular accident (CVA) as a cause of death, and hypertension, as compared to a reference group of nonhypertensive donors between the ages of 10 and 39 whose cause of death was not CVA, and whose creatinine was <1.5 mg/dL.1,8,17
Table 91–5. Marginal Cadaver Kidney Donors ||Download (.pdf)
Table 91–5. Marginal Cadaver Kidney Donors
|Donor age categories|
|CVA + HTN + Creat >1.5||•||•|
|CVA + HTN||•||•|
|CVA + Creat >1.5||•||•|
|HTN + Creat >1.5||•||•|
|None of the above||•|
The assessment of a donor liver before transplantation has been the subject of much research; however, clinically one still relies on a subjective interpretation of donor data and the macro- and microscopic appearance of the liver to decide whether to use the graft. More reliable predictors of graft function are required. Significant efforts have been made to try to assess donor grafts by evaluating different aspects of liver function, including the ability of the liver to synthesize proteins, metabolize drugs, secrete bile, produce high-energy phosphates, and by following the levels of markers of microvascular injury. To date, many donor organs that were previously not considered suitable for transplantation, “marginal” grafts, are now being used in selected circumstances. The marginal donors are identified based on demographic, clinical, laboratory, and histologic data. This includes donor age >70 years or <3 months, donor body weight over 100 kg, moderate or severe macrovesicular fat infiltration of the liver, and abnormal liver function tests. Serum aspartate aminotransferase (AST) >160 IU/L, serum sodium >160 mmol/L, donor stay in intensive care of more than 5 days, significant periods of hypotension (<60 mm Hg systolic BP for more than 30 minutes associated with a rise in serum AST), and significant systemic infection are all parameters considered to define marginal grafts. Important in the assessment of potential grafts is the presence of hepatic steatosis: increased donor age, obesity, and a history of high alcohol intake have all been associated with fatty infiltration.
Donor selection remains highly subjective, and in the absence of reliable laboratory tests the decision whether to use a marginal graft is left to the judgment of the transplant surgeon. The definition of what constitutes a “marginal” or “extended” graft will continue to vary between centers until reliable parameters are available for prospectively predicting early graft function.17,24,25