A number of centers have advocated the use of older heart donors to expand the donor pool and have reported no significant difference in 1-year graft survival with donors over the age of 40,10,11 over the age of 45,8,12 or over the age of 50.13 However, the number of older donors reported from these centers is small and only univariate analysis has been employed. The major multivariate analyses of the effects of increased donor age on both early and long-term survival after heart transplantation have been reported from UNOS,26 the CTRD,25,27 and the ISHLT Registry.28 Each of these reports has found decreased survival for recipients of hearts from donors over the age of 40. Similar findings have been reported from the ISHLT for recipients of lungs from donors over the age of 50.28 Although the odds ratio for 1-year mortality using heart donors over the age of 50 is approximately 1.5, this only translates into an increase in 1-year mortality from
10%-15% which contrasts quite favorably with a waiting list mortality of 20% or a predicted mortality of 40-50% with NYHA Class III-IV congestive heart failure. Therefore, we continue to utilize highly selected older donors particularly for older recipients or those who are critically ill (e.g., facing the prospect of death or mechanical assistance within the near future).
Recipients of hearts from female donors were initially felt to have worse outcomes than those receiving male donor hearts. In fact, data from both the ISHLT Registry28 and from UNOS26 would initially appear to support this assumption. However, a more thorough analysis by the TCRD27 has noted that this effect disappears when the data are normalized for body surface area, suggesting that small body size rather than gender alone produces the differential outcomes. Although the use of female donors does not effect survival following heart transplantation, data from the TCRD does show a significant increase in acute rejection29 and late recurrent rejection30 with the use of female donors. Based on these findings, we have generally avoided using undersized female hearts for larger male recipients and monitor the recipients of female donors (particularly female recipients) more closely for rejection.
The effect of racial mismatches in heart or lung transplantation has not been critically analyzed. Recently released data from UNOS suggest that using non-white donors does not significantly impact early (30 day) graft or patient survival, but does have a negative impact on 1-year graft and patient survival for both heart and lung recipients.26 However, donor size was not factored into the analysis. Since the impact of racial mismatch appears to be small, we have chosen not to let racial factors influence donor selection.
Donor-recipient size matching (D/R wt ratio > 0.8) has long been advocated for cardiac transplantation.31 Attempts to expand the donor pool have prompted many centers to expand their size matching criteria.32-35 Success has been achieved with D/R weight ratios as low as 0.5. However, the undersized donor adapts by utilizing chronotropic and isotropic reserves (increased heart rate and filling pressures) to maintain a normal cardiac output.32 This suggests that the undersized donor heart may have less functional reserve and be less able to tolerate any additional perioperative hemodynamic stress prior to undergoing adaptation. In fact, the group at the University of Virginia has shown that the use of undersized donors in critically ill status I patients may be associated with a worse outcome.37 The role of pulmonary hypertension and elevated pulmonary vascular resistance in donor selection remains controversial. However, most centers will attempt to avoid undersizing in this situation. We have taken the approach favored by most major centers of not undersizing below a D/R weight ratio of 0.7 for older donors, for female donors into male recipients, for recipients with elevated pulmonary vascular resistance (above 4 Wood units), or in those cases where a prolonged donor ischemic time is anticipated.
Oversizing of donors for adult recipients is rarely ever an issue. Additional space can be created by opening the pericardium into the pleural spaces to accommodate almost any oversized heart. Thus, there is no upper limit on the D/R weight ratio for adults. However, in the pediatric population there are some geometric size constraints. The Loma Linda group have reported successful transplantation with a D/R weight ratio of up to 4.038,39 and we have had similar experience. However, this requires leaving the sternum open for a prolonged period of time which may compromise pulmonary function or increase the risk of infection. We would suggest not exceeding a D/R weight ratio over 3.0 for most recipients.
The optimal technique of size-matching for pulmonary transplantation is not entirely clear. Very little data are available regarding the adverse consequences of over-sizing or under-sizing donor lungs. Anecdotal experience suggests that over-sizing the donor lung may lead to difficulties with intraoperative exposure, hemodynamic compromise, or wound closure, in addition to difficulty with postoperative clearing of secretions and atelectasis. Similarly, under-sizing of the donor lung may lead to persistent air leaks, pleural space problems, or empyema.6,40,41 Initial attempts to size lung donors according to weight proved inadequate since the usual D/R weight ratio often exceeded 1.5/1 because of the severe cachexia associated with end-stage lung disease. Comparisons of the donor and recipient chest measurements taken either directly (circumference at the xyphoid) or obtained from the chest radiographs (vertical apex to dome of diaphragm; transverse internal thoracic diameter at dome of diaphragm) have also been used for size matching. However, these measurements are affected by position (upright/supine) and level of inspiration or ventilation. Several studies have suggested that matching the estimated vital capacity (VC) or total lung capacity (TLC) based on height, age, sex, and race (not weight) of the donor to the predicted normal values for the recipient is the most appropriate method for size-matching.41-43
Size-matching should also consider both the disease process of the recipient and the type of transplant planned (single versus bilateral sequential). Single lung transplantation is generally recommended for patients with idiopathic pulmonary fibrosis, and older individuals (> 50 years of age) with chronic obstructive pulmonary disease (COPD) or alpha-1-antitrypsin (A1A) deficiency. For recipients with idiopathic pulmonary fibrosis or restrictive lung disease, matching the donor and recipient to within 20% of expected recipient lung volume (based on age, sex, height, and race) is recommended. For those with chronic obstructive lung disease or A1A deficiency, oversizing up to 25% is recommended because of the mediastinal shift caused by hyperinflation of the diseased native lung. In some centers, primary pulmonary hypertension patients receive single lung transplants. In these patients, a single lung that closely matches (± 20%) the size of the native lung is preferable.
Bilateral sequential single lung transplantation is performed in younger patients with COPD or alpha-1-antitrypsin deficiency (< 50 years of age), septic lung disease (cystic fibrosis, end-stage bronchiectasis), and for many patients with primary pulmonary hypertension. In most situations, size matching to within 20% of the recipient's estimated lung volume is recommended. Again, in patients with obstructive pulmonary disease, oversizing of up to 25% is well tolerated.
Critical to the selection process is a detailed history of the events leading to the death of the donor, the measures used to resuscitate the donor, a complete hemo-dynamic history, a summary of all medications used in the management of the donor, and any additional procedures performed on the donor since first being observed (e.g., special testing, surgery, transfusions, invasive monitoring, etc.).
Considerations include the cause of death and mechanism of injury as it may relate to the proposed organ of interest. In cases of blunt chest trauma, for example, the potential for an unsuspected cardiac or pulmonary contusion could be important.
The need and duration of cardiopulmonary resuscitation (CPR) is often discussed, but not always a factor if echocardiography at the time of donor assessment demonstrates preserved cardiac function.
While the presence of donor transmissible infectious disease that will adversely affect the recipient remains an absolute contraindication to transplantation, not all infectious diseases have a significant impact on recipient outcomes. Transmissible infectious diseases that predate the donor's terminal illness such as HIV, HTLV, hepatitis B, malaria, Jakob-Creutzfeldt's disease, and disseminated tuberculosis are absolute contraindications to organ donation.44 The presence of other infectious diseases such as hepatitis C, EBV, CMV, bacterial or fungal infections, are only relative contraindications to organ donation depending on whether the organism is treatable, its location (localized or disseminated), or the medical urgency for transplantation of the recipient.7
The presence of active sepsis has traditionally been viewed as an exclusion criteria for organ donation. The donor organ in these cases is thought to harbor the blood-borne pathogen, or be affected functionally by the myocardial depressant effect of endotoxins or exotoxins. While active bacterial sepsis continues to be viewed as a relative contraindication for organ donation, its risks to the recipient may not be as high as initially suspected.45 A report of 19 donors with positive blood cultures showed that bacterial transmission from donor heart to recipient occurs more frequently with gram negative organisms than with gram positive species.46 Additionally, no serious infectious sequelae occurred in recipients from
donors with gram positive bacteremia, although significant morbidity and mortality was found in organ recipients from donors with gram negative bacteremia.
Any history of encephalitis of unknown cause is an absolute contraindication for organ donation. However, pneumococcal meningitis is an occasional cause of brain death that does not preclude the use of donor organs for transplantation if the donor has received appropriate antibiotic therapy (usually high dose penicillin) for at least 24 hours prior to organ procurement. We have adhered to a policy of treating the recipient for 7-10 days with appropriate antibiotics to cover any documented bacteremia or infection noted in the donor.
Potential donors with active or hematologic malignancies should not be considered for organ donation, due to the risk of a malignancy being transmitted from the donor to a recipient.44,47 While most surgeons would consider a five year disease-free interval from a prior malignancy as a "cure", some cancers (e.g., breast, colon, or malignant melanoma) have been reported to develop late metastases (beyond five years). Therefore, Penn48 has strongly advocated obtaining a complete autopsy on any donor with a history of a prior malignancy.
Donors with low grade cutaneous malignancies such as basal cell carcinoma, low grade squamous carcinoma, or carcinoma-in-situ of the cervix have been utilized for transplantation, as they are not considered to be at high risk for occult metastatic disease to the transplanted organ.48,49 Donors with primary CNS tumors are also considered to be suitable for transplantation if it is unequivocally documented that the brain tumor is not a metastatic lesion.
Any social history which could increase the risk of transmissible infectious disease such as a multi-partner homosexual or heterosexual life style, prostitution, recent prison confinement, or history of recent IV drug abuse is a relative contraindication for organ donation, even in the face of negative serologic testing. These donors should be considered high risk, and should be used only in high risk recipients and only after obtaining the informed consent of the recipient.
Exposure of the donor to known cardiac toxins should alert the procurement team to obtain a more careful history of drug abuse or toxin exposure, and to more carefully evaluate their effects on the performance of the donor heart.
Acute and chronic alcoholism are known to impair myocardial function. Experience from several centers suggests that the results of heart transplantation from chronic alcoholic donors, even with normal function at the time of donor evaluation, is associated with a significantly worse outcome.50,51 A history of chronic alcoholism can be obtained in up to 20% of donors, and is associated with a reduction in 1-year survival from 95%-61%.51 A careful history regarding the level of alcohol consumption and any laboratory tests documenting the acute alcohol level should be obtained. We would avoid using donors with a history of heavy and prolonged alcohol abuse except in very extenuating circumstances for a critically ill recipient, and then only if the donor had normal function on echo.
Carbon monoxide poisoning causes approximately 1500 accidental deaths and about 2000 suicidal deaths in the United States each year, certainly a potential source of donors. However, in addition to causing cerebral ischemia and brain death, carbon monoxide also causes myocardial ischemia and possible necrosis by inhibiting oxygen transport and oxidative metabolism. Both hearts and lungs have been successfully transplanted using donors who died from carbon monoxide poisoning.52-55 However, severe myocardial ischemia and necrosis with early graft failure has also been reported.56 We would recommend not using the heart from donors with carbon monoxide poisoning unless the echocardiographic function is normal, the ECG shows no evidence of ischemia, and there is no biochemical evidence for myocardial necrosis. We would also avoid using the lungs from a smoke inhalation victim unless the chest xray is clear and the oxygen challenge is exceptional (pO2 > 400 on FI02=1.0).
Cocaine can cause coronary vasospasm, myocardial ischemia, myocardial infarction, malignant arrhythmias, and sudden death. While intravenous cocaine usage remains a strong contraindication to use of a donor,57 recreational nonintravenous cocaine usage does not preclude organ donation. In a series of 112 heart transplants, 16% of donors were found to have either a history of recreational cocaine usage or a positive toxicology screen without adverse effects on graft function, length of hospital stay, rejection, or survival.58
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