A simple bedside approach to therapeutic goals achievement during the management of deceased organ donors – An adapted version of the “VIP” approach

The disproportion between the supply and demand of transplant organs could be alleviated by improving the quality of clinical management of deceased potential donors. As a large number of donor losses by cardiac arrest occur due to hemodynamic instability, without instituting all essential maintenance measures, it is likely that the application of simplified potential donor maintenance protocols will help to decrease potential donor losses and increase the supply of organs for transplantation. The Ventilation, Infusion and Pumping (VIP) strategy is a mnemonic method that brings together key aspects of the restoration of oxygen delivery to tissues during hemodynamic instability: adequate mechanical Ventilation, volume Infusion and evaluation of heart Pump effectiveness. The inclusion of the additional initials, “P” and “S,” refers to Pharmacological treatment and Specificities involved in the etiology of shock. The use of simplified care standards can assist in adhering to essential potential donor management measures. Therefore, using a simplified method as the adapted VIP approach can contribute to improving management standards of potential organ donors and increasing the supply of organs for transplantation.     

Safe orthotopic transplantation of hearts harvested 24 hours after brain death and preserved for 24 hours

Objectives. The aim of this study was to demonstrate safe orthotopic transplantation of porcine donor hearts harvested 24?hours after brain death and preserved for 24?hours before transplantation. Design. Circulatory normalization of brain dead (decapitated) pigs was obtained using a new pharmacological regimen (n?=?10). The donor hearts were perfused at 8?°C in cycles of 15?min perfusion followed by 60?min without perfusion. The perfusate consisted of an albumin-containing hyperoncotic cardioplegic nutrition solution with hormones and erythrocytes. Orthotopic transplantation was done in 10 recipient pigs after 24?hours’ preservation. Transplanted pigs were monitored for 24?hours, then an adrenaline stress test was done. Results. All transplanted pigs were stable throughout the 24-hour observation period with mean aortic pressure around 80?mmHg and normal urine production. Mean right and left atrial pressures were in the range of 3–6 and 5–10?mmHg, respectively. Blood gases at 24?hours did not differ from baseline values. The adrenaline test showed a dose dependent response, with aortic pressure increasing from 98/70 to 220/150?mmHg and heart rate from 110 to 185 beats/min. Conclusion. Orthotopic transplantation of porcine hearts harvested 24?hours after brain death and preserved for 24?hours can be done safely.     

Optimisation of the organ donor and effects on transplanted organs: a narrative review on current practice and future directions

Mortality remains high for patients on the waiting list for organ transplantation. A marked imbalance between the number of available organs and recipients that need to be transplanted persists. Organs from deceased donors are often declined due to perceived and actual suboptimal quality. Adequate donor management offers an opportunity to reduce organ injury and maximise the number of organs than can be offered in order to respect the donor's altruistic gift. The cornerstones of management include: correction of hypovolaemia; maintenance of organ perfusion; prompt treatment of diabetes insipidus; corticosteroid therapy; and lung protective ventilation. The interventions used to deliver these goals are largely based on pathophysiological rationale or extrapolations from general critical care patients. There is currently insufficient high-quality evidence that has assessed whether any interventions in the donor after brain death may actually improve immediate post-transplant function and long-term graft survival or recipient survival after transplantation. Improvements in our understanding of the underlying mechanisms following brain death, in particular the role of immunological and metabolic changes in donors, offer promising future therapeutic opportunities to increase organ utilisation. Establishing a UK donor management research programme involves consideration of ethical, logistical and legal issues that will benefit transplanted patients while respecting the wishes of donors and their families.     

Modeling the economic benefit of targeted mild hypothermia in deceased donor kidney transplantation

Delayed graft function (DGF) in kidney transplant significantly increases inpatient and outpatient cost. Targeted, mild hypothermia in organ donors after neurologic determination of death significantly reduced the rate of DGF in a recent randomized controlled clinical trial. To assess the potential economic benefit of national implementation of donor hypothermia, rates of reduction DGF were combined with estimates of the impact of DGF on hospital cost and total health expenditure for standard and extended criteria donor organs (SCD and ECD). DGF increases the cost of the transplant episode by $9487 for ECD transplant and $10 342 for SCD transplant. Medicare recipients with DGF incur an additional $18 513 spending for ECD and $14 948 in SCD transplants over the first year. An absolute reduction in DGF rate after kidney transplantation consistent with trial results (ECD 25%, SCD 7%) has the potential to lower annual hospital cost for kidney transplant by $13 178 746 and annual Medicare spending by $20 970 706 compared to standard donor management practice using static cold storage. Targeted mild hypothermia improves care of renal transplant patients by safely reducing DGF rates in both ECD and SCD transplant. Broader application of this safe, effective, and low‐cost intervention could reduce healthcare expenditures for providers and insurers.     

Optimized donor management and organ preservation before kidney transplantation

Kidney transplantation is a major medical improvement for patients with end‐stage renal disease, but organ shortage limits its widespread use. As a consequence, the proportion of grafts procured from extended criteria donors (ECD) has increased considerably, but this comes along with increased rates of delayed graft function (DGF) and a higher incidence of immune‐mediated rejection that limits organ and patient survival. Furthermore, most grafts are derived from brain dead organ donors, but the unphysiological state of brain death is associated with significant metabolic, hemodynamic, and pro‐inflammatory changes, which further compromise patient and graft survival. Thus, donor interventions to preserve graft quality are fundamental to improve long‐term transplantation outcome, but interventions must not harm other potentially transplantable grafts. Several donor pretreatment strategies have provided encouraging results in animal models, but evidence from human studies is sparse, as most clinical evidence is derived from single‐center or nonrandomized trials. Furthermore, ethical matters have to be considered especially concerning consent from donors, donor families, and transplant recipients to research in the field of donor treatment. This review provides an overview of clinically proven and promising preclinical strategies of donor treatment to optimize long‐term results after kidney transplantation.     

Living Anonymous Liver Donation: Case Report and Ethical Justification

Most living organ donations are from genetically or emotionally related donors. Although some transplant centers are willing to accept donations from living anonymous kidney donors (LAKDs), very few centers will accept donations from living anonymous liver donors (LALDs). The difference in acceptance rates is primarily due to the greater risk in liver donation, which is estimated to be 10-fold that of the risk in kidney donation. We present a case of donation from a LALD, the first reported in Canada. There are currently no established standards for LALDs. Our criteria for the ethical acceptability of LALDs require such donors to be physically healthy, mentally competent, altruistic, highly motivated, well-informed and able to give voluntary consent to donation. Another major ethical criterion is that the likely psychological benefit to the LALD balances the physical risks. Our case demonstrates that transplants from LALDs are medically successful and ethically justified under certain conditions.     

A stroke volume-based fluid resuscitation protocol decreases vasopressor support and may increase organ yield in brain-dead donors

Brain-dead donors are frequently hypovolemic and hypotensive requiring vasopressor support. We studied a stroke volume-based fluid resuscitation and vasopressor weaning protocol prospectively on 64 hypotensive donors, with a recent control cohort of 30 hypotensive donors treated without a protocol. Stroke volume was measured every 30 minutes for 4 hours by pulse contour analysis or esophageal Doppler. A 500 mL saline fluid bolus was infused over 30 minutes and repeated if the stroke volume increased by 10%. No fluid was infused if the stroke volume did not increase by 10%. Vasopressors were weaned every 10 minutes if the mean arterial pressure was greater than 65 mm Hg. The protocol group received 1937 ± 906 mL fluid compared to 1323 ± 919 mL in the control group (P = .003). Mean time on vasopressors was decreased from 957.6 ± 586.2 to 176.3 ± 82.2 minutes (P<.001). Donors in the protocol group were more likely to donate four or more organs than donors in the control group (OR = 4.114, 95% Confidence Interval (CI) = 1.003-16.876). While more organs were transplanted per donor in the protocol group (3.39 ± 1.52) than in the control group (2.93 ± 1.44) (P = .268), the difference did not reach statistical significance. A goal-directed fluid resuscitation protocol decreased organ ischemia and may increase organs transplanted.     

The Life-Years Saved by a Deceased Organ Donor

Understanding the additional life-years given to patients by deceased organ donors is necessary as substantial investments are being proposed to increase organ donation. Data were drawn from the Scientific Registry of Transplant Recipients. All patients placed on the wait-list as eligible to receive or receiving a deceased donor solid organ transplant between 1995 and 2002 were studied. The benefit of transplant was determined by the difference in the expected survival experiences of transplant recipients and candidates expecting transplant soon. An average organ donor provides 30.8 additional life-years distributed over an average 2.9 different solid organ transplant recipients, whereas utilization of all solid organs from a single donor provides 55.8 additional life-years spread over six organ transplant recipients. The relative contribution of the different organs to the overall life-year benefit is higher for liver, heart and kidney, and lowest for lung and pancreas. The life-year losses from unprocured and unused organs are comparable to suicide, congenital anomalies, homicide or perinatal conditions and half that of HIV. Approximately 250,000 additional life-years could be saved annually if consent for potential deceased donors could be increased to 100%. Therefore, increasing organ donation should be considered among our most important public health concerns.     

Center‐Level Patterns of Indicated Willingness to and Actual Acceptance of Marginal Kidneys

UNet^SM, the UNOS data collection and electronic organ allocation system, allows centers to specify organ offer acceptance criteria for patients on their kidney waiting list. We hypothesized that the system might not be fully utilized and that the criteria specified by most transplant centers would be much broader than the characteristics of organs actually transplanted by those centers. We analyzed the distribution of criteria values among waitlist patients (N = 304 385) between January 2000 and February 2009, mean criteria values among listed candidates on February 19, 2009 and differences between a center's specified criteria and the organs it accepted for transplant between July 2005 and April 2009. We found wide variation in use of criteria variables, with some variables mostly or entirely unused. Most centers specified very broad criteria, with little within‐center variation by patient. An offer of a kidney with parameters more extreme than the maximum actually transplanted at that center was designated a ‘surplus offer’ and indicated a potentially avoidable delay in distribution. We found 7373 surplus offers (7.1% of all offers), concentrated among a small number of centers. The organ acceptance criteria system is currently underutilized, leading to possibly avoidable inefficiencies in organ distribution.     

Evidence‐based development of liver allocation: a review

Liver transplantation has undergone a rapid evolution from a high‐risk experimental procedure to a mainstream therapy for thousands of patients with a wide range of hepatic diseases. Its increasing success has been accompanied by progressive imbalance between organ donor supply and the patients who might benefit. Where demand outstrips supply in transplantation, a system of organ allocation is inevitably required to make the wisest use of the available, but scarce, organs. Early attempts to rationally allocate donor livers were particularly hampered by lack of available and suitable data, leading to imperfect solutions that created or exacerbated inequities in the system. The advent and maturation of evidence‐based predictors of waiting list mortality risk led to more objective criteria for liver allocation, aided by the increasing availability of data on large numbers of patients. Until now, the vast majority of allocation systems for liver transplantation have relied on estimation of waiting list mortality. Evidence‐based allocation systems that incorporate measures of post‐transplant outcomes are conceptually attractive and these transplant benefit‐based allocation systems have been developed, modeled, and subjected to computer simulation. Future implementations of benefit‐based liver allocation await continued refinement and additional debate in the transplant community.     

Successful transplantation of organs retrieved from a donor with enterococcal endocarditis

We report on a patient with an extensive cerebral infarction secondary to enterococcal endocarditis that, in spite of adequate antibiotic treatment, evolved to brain death. The patient was evaluated as a potential organ donor; renal and liver function were normal and both liver and kidneys appeared normal on ultrasonographic examination. When negativity of serial blood and urine cultures was ascertained, liver and kidneys were retrieved for transplantation. The organs were transplanted into three recipients with good results after 14 months of follow-up. All of the recipients received antibiotic prophylaxis against Enterococcus faecalis. None of them has presented infectious complications to date. This case emphasizes that patients with enterococcal endocarditis may be potential organ donors provided both donor and recipients are adequately treated. This is especially important when organs are urgently needed. Received: 3 February 1998 Received after revision: 24 March 1998 Accepted: 15 April 1998     

Deceased Organ Donor Characteristics and Clinical Interventions Associated with Organ Yield

While the function of each organ is used by each transplant team to assess suitability for transplantation, little is known about the donor characteristics and clinical interventions that contribute toward overall organ transplantation potential. We conduct a retrospective review of United Network for Organ Sharing (UNOS) deceased donor registry data from January 2005 to December 2006. This registry contains all deceased donors from whom organs were recovered during this time period (n = 15  601). Ordinary least-squares (OLS) regression models using variables in the registry are estimated to predict the number of organs transplanted. Outcome is the number of organs transplanted per donor. Organ yield is found to depend significantly on donor age, anoxia as cause of death, history of myocardial infarction (MI), hypertension and/or diabetes, body mass index (BMI), B or AB blood type, cocaine and/or cigarette use and hepatitis infection (p < 0.01). In addition, the clinical interventions of steroid administration, desmopressin (DDAVP) and diuretic usage, as well as oxygenation, are associated with organ yield. Both intrinsic donor characteristics and medical management practice are observed to be highly variable across organ procurement organizations (OPOs). These findings may provide important information to explore and assess the efficacy of clinical interventions, compare OPO performance and point to best practices.     

Non-heart beating organ donation: overview and future perspectives

New indications for organ transplantation combined with a stagnating number of available donor grafts have severely lengthened the waiting list for almost all types of transplantations. This has led to a renewed interest in non-heart beating (NHB) donation, as a possible solution to bridge the gap between supply and demand. In this review, we present an overview of current NHB donation practice, outcome, existing problems and future perspectives. We focus on possible improvements in donor management, recipient care and new methods of organ preservation that may be better suited for these marginal organs. Successful institution of NHB protocols depends on adapting current transplantation practice at all levels, which is one of the greatest challenges for researchers and professionals in this interesting re-emerging field.     

Caution: deceased donor organ commercialism!

In the past 3 years there have been attempts to counter the international campaign against a market in organs from the living. In parallel to these attempts, support for a market in organs from the deceased has gained some traction. In this article we describe the various forms of this phenomenon, analyze its implications, and call upon policy makers to take steps to halt its progress.     

Expanding the Donor Pool: Can the Spanish Model Work in the United States?

Since the creation of the Organizacion Nacional de Trasplantes (ONT) in 1989, the organ donation rate in Spain has doubled. Although often attributed to improved donor recruitment efforts, this increase may also represent higher utilization of marginal donors. Therefore, age-related donor recruitment in Spain and the US was evaluated. Data from the ONT, the US Scientific Registry of Transplant Recipients (SRTR), the US Census Bureau, and the Tempus databank of Spain's Instituto Nacional de Estadistica (INE) were analyzed. Between 1989 and 1999, the number of donors in Spain increased from 14.3 to 33.7 per million population (pmp; 136% increase) compared with an increase in the US from 16.2 to 21.5 donors pmp (33%). The largest difference between Spain and the US in the increased number of donors was in the 45-year-old group, representing 30.3% of donors in Spain in 1999 (44 donors pmp). If the US increased its older donor rates to match Spain's, an incremental 1235 donors per year would be realized. The high Spanish organ donation rates are largely attributable to increased use of older donors. Utilizing similar proportions of older donors in the US would increase the donor pool by almost 40%.     

A plea for uniform European definitions for organ donor potential and family refusal rates

Conversion of potential organ donors to actual donors is negatively influenced by family refusals. Refusal rates differ strongly among countries. Is it possible to compare refusal rates in order to be able to learn from countries with the best practices? We searched in the literature for reviews of donor potential and refusal rates for organ donation in intensive care units. We found 14 articles pertinent to this study. There is an enormous diversity among the performed studies. The definitions of potential organ donors and family refusal differed substantially. We tried to re‐calculate the refusal rates. This method failed because of the influence caused by the registered will on donation in the Donor Register. We therefore calculated the total refusal rate. This strategy was also less satisfactory considering possible influence of the legal consent system on the approach of family. Because of lack of uniform definitions, we can conclude that the refusal rates for organ donation can not be used for a sound comparison among countries. To be able to learn from well‐performing countries, it is necessary to establish uniform definitions regarding organ donation and registration of all intensive care deaths.     

Solving the Organ Shortage Crisis: The 7th Annual American Society of Transplant Surgeons' State-of-the-Art Winter Symposium

The 2007 American Society of Transplant Surgeons' (ASTS) State-of-the-Art Winter Symposium entitled, 'Solving the Organ Shortage Crisis' explored ways to increase the supply of donor organs to meet the challenge of increasing waiting lists and deaths while awaiting transplantation. While the increasing use of organs previously considered marginal, such as those from expanded criteria donors (ECD) or donors after cardiac death (DCD) has increased the number of transplants from deceased donors, these transplants are often associated with inferior outcomes and higher costs. The need remains for innovative ways to increase both deceased and living donor transplants. In addition to increasing ECD and DCD utilization, increasing use of deceased donors with certain types of infections such as Hepatitis B and C, and increasing use of living donor liver, lung and intestinal transplants may also augment the organ supply. The extent by which donors may be offered incentives for donation, and the practical, ethical and legal implications of compensating organ donors were also debated. The expanded use of nonstandard organs raises potential ethical considerations about appropriate recipient selection, informed consent and concerns that the current regulatory environment discourages and penalizes these efforts.     

Growth of a nation part II: impact of recipient obesity on whole-organ pancreas transplantation

Obesity has reached epidemic proportions in the USA. Consequently, there is an increasing number of obese diabetic patients who would otherwise be appropriate candidates for pancreas transplantation (PTx). This is a retrospective study of all PTx performed at Indiana University between 2003 and 2009 (n = 308) comparing recipients with body mass index (BMI) < 25, 25-29.9, and ≥30 kg/m(2) Data included recipient and donor demographics, seven and 90-d graft loss, one-yr pancreas, kidney (for SPK only) and patient survival, causes of graft loss and death, peak amylase and lipase, length of stay, readmissions, complications, HbA1C, and c-peptide. Of the 308 PTx, 100 (32%) were overweight and 42 (14%) were obese. Obese recipients were older and more likely to be men. Donor demographics were similar. There was no difference in seven-d or 90-d graft loss, one-yr pancreas, kidney or patient survival, cause of graft loss or death, 30-d peak amylase or lipase, HbA1C, or C-peptide. The incidence of post-transplant technical, immunological and infectious complications was similar except for an increased incidence of cytomegalovirus infection in the obese group. Two recipients returned to insulin therapy despite normal C-peptide levels. Although technically challenging, PTx can be successful in select obese recipients with similar results compared to normal BMI recipients.