Experience of heart transplantation from hemodynamically unstable brain-dead donors with extracorporeal support

Yang H‐Y, Lin C‐Y, Tsai Y‐T, Lee C‐Y, Tsai C‐S. Experience of heart transplantation from hemodynamically unstable brain‐dead donors with extracorporeal support. Abstract: The shortage of organ donors remains a major problem for transplantation worldwide. Potential donors after brain death may become hemodynamically unstable, despite maximal medical management, which ultimately leads to failure of organ procurement. We reviewed the medical records of five brain‐dead potential donors who presented with hemodynamic instability despite maximal medical management that were supported by extracorporeal circulation membrane oxygenation (ECMO). The outcomes of heart recipients were reviewed. The five donors under extracorporeal support finished a declaration of brain death without cardiac arrest. Donor organs, including three hearts, nine kidneys, and four livers, were harvested from the five donors under ECMO support. All three heart recipients recovered uneventfully after one yr of follow‐up. Our experience indicates that potential donors may experience central‐failure‐related hemodynamic instability after brain death, despite maximal medical support, which leads to a fatal result. Beyond medical management, prompt and early extracorporeal support for salvaging brain‐dead potential donors from cardiac death seems to be a practical strategy to increase the donor pool and preserve donor organs.     

Impact of deceased donor multidrug‐resistant bacterial organisms on organ utilization

The extent to which donor multidrug‐resistant organisms (MDROs) affect organ utilization remains unclear. We performed a retrospective cohort study at 4 transplant centers between 2015 and 2016 to evaluate this question. All deceased donors who donated at least one organ were included. Exposed donors had at least one MDRO on culture. Unexposed donors had no MDRO‐positive cultures. Only cultures obtained during the donor's terminal hospitalization were evaluated. Multivariable regression was used to determine the association between donor MDRO and (1) number of organs transplanted per donor and (2) the match run at which each organ was accepted. Subsequently, we restricted the analysis to donors with MDR‐Gram‐negative (GN) organisms. Of 440 total donors, 29 (7%) donors grew MDROs and 7 (2%) grew MDR‐GNs. There was no significant association between donor MDRO and either measure of organ utilization. However, donor MDR‐GNs were associated with a significant reduction in the number of organs transplanted per donor (incidence rate ratio 0.43, 95% confidence interval [CI] 0.39‐0.48, P < .01), and organs were accepted significantly further down the match list (relative count 5.08, 95% CI 1.64‐15.68, P = .01). Though donor MDR‐GNs were infrequent in our study, their growing prevalence could meaningfully reduce the donor pool over time.     

Cardio‐pulmonary resuscitation of brain‐dead organ donors: a literature review and suggestions for practice

“Organ preserving cardiopulmonary resuscitation (OP‐CPR)” is defined as the use of CPR in cases of cardiac arrest to preserve organs for transplantation, rather than to revive the patient. Is it ethical to provide OP‐CPR in a brain‐dead organ donor to save organs that would otherwise be lost? To answer this question, we review the literature on brain‐dead organ donors, conduct an ethical analysis, and make recommendations. We conclude that OP‐CPR can benefit patients and families by fulfilling the wish to donate. However, it is an aggressive procedure that can cause physical damage to patients, and risks psychological harm to families and healthcare professionals. In a brain‐dead organ donor, OP‐CPR is acceptable without specific informed consent to OP‐CPR, although advance discussion with next of kin regarding this possibility is strongly advised. In a patient where brain death is yet to be determined, but there is known wish for organ donation, OP‐CPR would only be acceptable with a specific informed consent from the next of kin. When futility of treatment has not been established or it is as yet unknown if the patient wished to be an organ donor then OP‐CPR should be prohibited, in order to avoid any conflict of interest.     

The utilization of solid organs for transplantation in the setting of infection with multidrug‐resistant organisms: an expert opinion

Organ transplantation remains the optimal treatment for many patients suffering from end‐stage organ disease. Increasing numbers of patients admitted to intensive care units, among them potential heart‐beating, brain‐dead organ donors, are exposed to infections with multidrug‐resistant organisms, in particular carbapenem‐resistant Klebsiella pneumoniae (CR‐KP). An extensive literature search failed to reveal any information regarding the eligibility for transplantation of organs from such donors. For this reason, in 2009, the Israel Transplant Center, together with the Israeli Society for Infectious Diseases, established a working group with the intention of developing a national‐specific approach to the use of these organs. In this viewpoint article, we present an algorithm based on expert opinion and our clinical experience with a donor who was found to be an asymptomatic carrier of CR‐KP.     

Donor pre‐treatment in clinical kidney transplantation: a critical appraisal

Kidney transplantation represents one of the medical achievements of the 20th century. However, its continued success is limited by the increasing shortage of donor grafts. As a result, more kidney grafts from marginal donors are being considered for transplantation, with concomitantly more initial graft injury and limited organ and patient survival. This has led to an increased need for interventions aiming to optimize and preserve graft quality. Interventions within the donor may protect against ischemia/reperfusion injury, and therefore, donor pre‐treatment is a promising strategy to increase graft function and survival. During the last decade, diverse donor pre‐treatment interventions have been explored in animal studies. Moreover, the first human trials concerning donor pre‐treatment in kidney transplantation have provided encouraging results. Unfortunately, it remains difficult to determine how and where to intervene in the multifactorial and complex processes that affect the donor kidney. Moreover, ethical matters play a critical role in donor interventions, and pre‐treatment should principally not have any potentially unfavorable effects on other organs to be transplanted or on the living donor. This review provides an overview of promising therapeutical strategies for donor pre‐treatment in kidney transplantation and discusses the clinical trials that have been conducted thus far.     

Effect of Active and Early Possible Organ and Tissue Donor Detection in the Emergency Room in a University Hospital

PurposeThe emergency room of the hospital is the gateway for patients with severe brain damage due to neurologic or cardiac conditions such as stroke or cardiac arrest. The main purpose is to design an active registry of patients, in the emergency room, to facilitate the detection and follow-up of potential donors according to their clinical evolution.Material and MethodsThis is a 1-year prospective study from May 2017 to May 2018 with a register for detection of patients admitted to the emergency room with severe brain damage (Glasgow Coma Scale score ≤ 8), with active follow-up until hospital discharge, who might have died or otherwise become possible organ and tissue donors.ResultsOne hundred sixty-six (107 men and 59 women) patients met the inclusion criteria: (1) 30.7% recovered from cardiac arrest; (2) 31.3% from stroke; (3) 16.9% from traumatic brain injury and multiple trauma; (4) 10.2% had decreased level of consciousness; (5) 4.8% had other cardiac conditions; and (6) 6.0% had other diagnoses.Seventy-seven out of 166 patients (46.4%) were evaluated as possible organ and tissue donors, with 37 out of 77 (48.0%) of the possible donors becoming real donors. This means that 37 out of 166 (22.3%) of the possible donors admitted to the emergency room became real donors. Twenty-two out of 77 of the patients (28.6%) evaluated had clinical contraindications for donation and in 18 out of 77 (23.4%), there was family refusal for any kind of organ or tissue donation. This record allowed the generation of the following organs and tissues: 4 hearts, 19 livers, 14 lungs, 52 kidneys, 2 pancreata, 29 corneas, 19 donations of bone allografts, 15 donations of skin tissue, 14 donations of valvular allografts, and 11 vascular allografts.ConclusionsThe early and active possible donors registry at the emergency room has facilitated early detection and allow adequate follow-up and evaluation of possible organ and tissue donors.     

Organ Donation and Utilization in the United States: 1998–2007

Organ transplantation remains the only life-saving therapy for many patients with organ failure. Despite the work of the Organ Donation and Transplant Collaboratives, and the marked increases in deceased donors early in the effort, deceased donors only rose by 67 from 2006 and the number of living donors declined during the same time period. There continues to be increases in the use of organs from donors after cardiac death (DCD) and expanded criteria donors (ECD). This year has seen a major change in the way organs are offered with increased patient safety measures in those organ offers made by OPOs using DonorNet^©. Unfortunately, the goals of 75% conversion rates, 3.75 organs transplanted per donor, 10% of all donors from DCD sources and 20% growth of transplant center volume have yet to be reached across all donation service areas (DSAs) and transplant centers; however, there are DSAs that have not only met, but exceeded, these goals. Changes in organ preservation techniques took place this year, partly due to expanding organ acceptance criteria and increasing numbers of ECDs and DCDs. Finally, the national transplant environment has changed in response to increased regulatory oversight and new requirements for donation and transplant provider organizations.     

In situ liver splitting under extracorporeal membrane oxygenation in brain‐dead donor

Hemodynamic instability is generally considered as a contraindication to liver splitting, in particular when using an in situ technique. We describe the cases of two young donors with brain death in whom refractory cardiac arrest and hemodynamic instability were supported by veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO), allowing uneventful in situ splitting. Two adult and two pediatric liver recipients were successfully transplanted with immediate graft function. Favorable outcomes were also observed for the other transplanted organs, including one heart, two lungs, and four kidneys. Refractory cardiac arrest and hemodynamic instability corrected by VA‐ECMO should not be considered as a contraindication to in situ liver splitting.     

The Influence of End‐of‐Life Care on Organ Donor Potential

Many patients with acute devastating brain injury die outside intensive care units and could go unrecognized as potential organ donors. We conducted a prospective observational study in seven hospitals in the Netherlands to define the number of unrecognized potential organ donors outside intensive care units, and to identify the effect that end‐of‐life care has on organ donor potential. Records of all patients who died between January 2013 and March 2014 were reviewed. Patients were included if they died within 72 h after hospital admission outside the intensive care unit due to devastating brain injury, and fulfilled the criteria for organ donation. Physicians of included patients were interviewed using a standardized questionnaire regarding logistics and medical decisions related to end‐of‐life care. Of the 5170 patients screened, we found 72 additional potential organ donors outside intensive care units. Initiation of end‐of‐life care in acute settings and lack of knowledge and experience in organ donation practices outside intensive care units can result in under‐recognition of potential donors equivalent to 11–34% of the total pool of organ donors. Collaboration with the intensive care unit and adjusting the end‐of‐life path in these patients is required to increase the likelihood of organ donation.     

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.     

Allowing HIV‐Positive Organ Donation: Ethical,Legal and Operational Considerations

Case reports of kidney transplantation using HIV‐positive (HIV+) donors in South Africa and advances in the clinical care of HIV+ transplant recipients have drawn attention to the legal prohibition of transplanting organs from HIV+ donors in the United States. For HIV+ transplant candidates, who face high barriers to transplant access, this prohibition violates beneficence by placing an unjustified limitation on the organ supply. However, transplanting HIV+ organs raises nonmaleficence concerns given limited data on recipient outcomes. Informed consent and careful monitoring of outcome data should mitigate these concerns, even in the rare circumstance when an HIV+ organ is intentionally transplanted into an HIV‐negative recipient. For potential donors, the federal ban on transplanting HIV+ organs raises justice concerns. While in practice there are a number of medical criteria that preclude organ donation, only HIV+ status is singled out as a mandated exclusion to donation under the National Organ Transplant Act (NOTA). Operational objections could be addressed by adapting existing approaches used for organ donors with hepatitis. Center‐specific outcomes should be adjusted for HIV donor and recipient status. In summary, transplant professionals should advocate for eliminating the ban on HIV+ organ donation and funding studies to determine outcomes after transplantation of these organs.     

Outcome of Transplantation Using Organs From Donors Infected or Colonized With Carbapenem‐Resistant Gram‐Negative Bacteria

Donor‐derived infections due to multidrug‐resistant bacteria are a growing problem in solid organ transplantation, and optimal management options are not clear. In a 2‐year period, 30/214 (14%) recipients received an organ from 18/170 (10.5%) deceased donors with infection or colonization caused by a carbapenem‐resistant gram‐negative bacteria that was unknown at the time of transplantation. Among them, 14/30 recipients (47%) received a transplant from a donor with bacteremia or with infection/colonization of the transplanted organ and were considered at high risk of donor‐derived infection transmission. The remaining 16/30 (53%) recipients received an organ from a nonbacteremic donor with colonization of a nontransplanted organ and were considered at low risk of infection transmission. Proven transmission occurred in 4 of the 14 high‐risk recipients because donor infection was either not recognized, underestimated, or not communicated. These recipients received late, short or inappropriate posttransplant antibiotic therapy. Transmission did not occur in high‐risk recipients who received appropriate and prompt antibiotic therapy for at least 7 days. The safe use of organs from donors with multidrug‐resistant bacteria requires intra‐ and inter‐institutional communication to allow appropriate management and prompt treatment of recipients in order to avoid transmission of infection.     

Organ donor management and organ outcome: a 6-year review from a Level I trauma center

A retrospective review of 114 solid organ donors over a 6-year period (1982-1987) was undertaken to identify problems in organ donor management and determine outcome of donated organs. Admission GCS was less than or equal to 4 in 84% of the donors. Complications included hypotension (81%), multiple transfusion requirements (63%), diabetes insipidus (53%), DIC (28%), arrhythmias (27%), cardiac arrest requiring CPR (25%), pulmonary edema (19%), hypoxia (11%), acidosis (11%), seizures (10%), and positive bacterial cultures (10%). Only 18% of organs were procured within 3 hours of brain death; 23% were procured more than 6 hours later. Six patients excluded from this study suffered cardiovascular collapse before their organs could be retrieved. From 114 organ donors, consent was obtained to procure 224 kidneys, 77 livers, 62 hearts, 35 pancreata, and ten heart-lung units. All 224 donated kidneys were procured and 202 were ultimately transplanted. Of 77 donated livers, 32 were procured; 31 transplanted. Of 62 donated hearts, 38 were procured; 29 transplanted and nine used for valves. Ten heart-lung units were donated; six were procured and transplanted. Of 35 donated pancreata, 11 were procured; only five were transplanted. Reasons for failure of donated organs to be procured or transplanted included abnormal organ characteristics, lack of compatible recipients, unavailability of surgical teams, organ injury during procurement, intraoperative arrest, and anatomic limitations precluding multiple organ procurement. This study identifies characteristics of organ donors and common organ-threatening complications. Rapid and continuing resuscitation of clinically brain dead trauma victims is mandatory.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intra‐arrest formation of right‐heart thrombi – a case illustrated by real‐time ultrasonography

The presence of free‐floating right‐heart thrombus has been reported in a cardiac arrest patient in the periarrest period. Free‐floating right atrial thrombus is a rare phenomenon seen in patients developing severe pulmonary embolism, and is associated with increased mortality. However, there have been no previously reported cases of right‐heart thrombus formation during a resuscitated cardiac arrest. We present the pre‐hospital case of a woman in the clinical setting of cardiogenic shock due to acute myocardial infarction who developed asystolic cardiac arrest on the scene. Recent implementation of ultrasonography into the regional pre‐hospital care protocol enabled sonographic investigation before and during cardiac arrest. This allowed detection of right atrial septal thrombus formation in the course of advanced life support and its migration through the tricuspid valve. The pathophysiological consequences, clinical significance and potential therapeutic options are discussed.     

Cardiac arrest in the organ donor does not negatively influence recipient survival after heart transplantation.

OBJECTIVE: Cardiac arrest in the organ donor raises concerns about the possibility of ischemic cardiac damage. We evaluated the outcome of heart transplantation in patients receiving an organ from donors who had suffered a period of cardiac arrest. METHODS: Demographics, operative details and outcome data were obtained retrospectively. Actuarial survival was reported using Kaplan-Meier analysis and compared with the log rank test. Cox proportional hazards regression was used to model risk adjusted survival. RESULTS: Between 1 January 1991 and 1 November 2004 38 patients were transplanted with hearts from multiorgan donors who were resuscitated after a cardiac arrest. The mean (standard deviation) duration of cardiac arrest was 15 (8)min. The interval between donor cardiac arrest and organ excision was 69 (5)h. The 30-day mortality was 2.6% (1/38). In the same interim 566 patients underwent cardiac transplantation with hearts from organ donors without a cardiac arrest. Median time to follow up was 61 months (IQR 15-166). One and 5-year survival comparing the arrest and non-arrest groups was 94.2% versus 83.6% and 79.8% versus 74.5%, respectively, p=0.35. Donor cardiac arrest was not an adverse predictor of mortality on multivariate analysis, the adjusted odds ratio was 0.86 (95% CI 0.60-1.25, p=0.42). CONCLUSIONS: With careful case selection, there was no evidence that survival after cardiac transplantation was worse following a period of cardiac arrest in the organ donor. A history of cardiac arrest in the organ donor should not exclude an organ from being considered for transplantation.     

The number of lung transplants can be safely doubled using extended criteria donors; A single‐center review

Relaxing the standard lung donor criteria may significantly increase the reported 15% organ yield but post‐transplant recipient outcome should be carefully monitored. Charts from all consecutive deceased organ donors within our hospital network were reviewed over a 2‐year period. Reasons for lung refusals and number of lungs transplanted were analysed. Hospital outcome including early recipient survival was compared between standard‐ and extended criteria donors. Out of 283 referrals, 164 (58%) qualified as donor of any organ. The majority (65.9%) of these effective donors were declined for lung donation because of chest X‐ray abnormalities (20%), age >70 years (13%), poor oxygenation (10%), or aspiration (9%). Out of 56 (34.1%) accepted lung donors, 50 transplants were performed at our center, 23 from standard criteria donors versus 27 from extended criteria donors. There were no significant differences in hospital outcome and in early survival between lung recipients from both donor groups. Lung acceptance rate (34.1%) in our donor network is 10–20% higher than reported figures. The number of lung transplants in our center doubled by accepting extended criteria donors. This policy did not negatively influence our results after lung transplantation.     

Plasma B-type natriuretic peptide levels in cardiac donors

Abstract: Introduction: Elevated levels of plasma brain natriuretic peptide (BNP) and amino‐terminal BNP (NT‐proBNP) are associated with adverse cardiac outcomes. It is not known whether BNP and NT‐proBNP levels in heart donors can aid in selection and predict outcomes in transplant recipients. Methods: Plasma BNP and NT‐proBNP were measured in 32 organ donors prior to removal from life‐support systems. Twelve hearts were accepted and 20 hearts were declined (no suitable recipient – 12, probable coronary artery disease – four, abnormal echocardiogram – three, other medical reasons – one). Records of heart transplant recipients were reviewed for: survival at 30 d, length of intensive care stay and need for intra‐aortic balloon counter‐pulsation (IABP). Results: Donors were divided into three groups – Group 1 (n = 12): accepted hearts; Group 2 (n = 12): acceptable hearts not transplanted for logistic reasons; Group 3 (n = 8): declined because of probable cardiac disease. BNP and NT‐proBNP levels were significantly lower in donors with acceptable hearts (n = 24) compared with those with unacceptable hearts (n = 8) (p = 0.02 and 0.032, respectively). Of the 12 patients transplanted, four suffered a suboptimal outcome (two died, one required inotropic support and IABP, one prolonged hospitalization) while eight had good outcomes with no significant difference in BNP/NT‐proBNP levels between these groups. Conclusion: BNP and NT‐proBNP levels were lower in organ donors whose hearts were acceptable for transplantation compared with those whose hearts were unsuitable. Measuring natriuretic peptides may be a useful adjunctive tool in the selection of donor hearts. We feel that further studies are warranted.     

Donor‐Derived Strongyloides stercoralis Infection in Solid Organ Transplant Recipients in the United States, 2009–2013

Infection with Strongyloides stercoralis is typically asymptomatic in immunocompetent hosts, despite chronic infection. In contrast, immunocompromised hosts such as solid organ transplant recipients are at risk for hyperinfection syndrome and/or disseminated disease, frequently resulting in fatal outcomes. Infection in these recipients may result from reactivation of latent infection or infection through transmission from an infected donor. We describe the Centers for Disease Control and Prevention's experience with seven clusters of donor‐derived infection from 2009 to 2013. Six of the seven (86%) donors were born in Latin America; donor screening was not performed prior to organ transplantation in any of these investigations. Eleven of the 20 (55%) organ recipients were symptomatic, two of whom died from complications of strongyloidiasis. We also describe the New York Organ Donor Network (NYODN) experience with targeted donor screening from 2010 to 2013. Of the 233 consented potential donors tested, 10 tested positive for Strongyloides antibody; and 18 organs were transplanted. The majority (86%) of the donors were born in Central or South America. Fourteen recipients received prophylaxis after transplantation; no recipients developed strongyloidiasis. The NYODN experience provides evidence that when targeted donor screening is performed prior to transplantation, donor‐derived infection can be averted in recipients.     

Donor‐Derived Bacteremia in Liver Transplant Recipients Despite Antibiotic Prophylaxis

As the disparity between the number of candidates listed for transplant and the number of donors continues to grow, marginal organ donors are increasingly utilized. This includes bacteremic donors which may carry an increased risk of transmission of infection. It is recommended that recipients of organs from bacteremic donors receive antibiotic prophylaxis based on the susceptibilities of the donor isolate to prevent transmission. Here, we present four cases of donor‐derived bacteremia, despite appropriate antimicrobial prophylaxis, in four liver transplant recipients. Transmitted pathogens included Staphylococcus aureus in two cases, and Escherichia coli and Group B Streptococcus each in one case. Interestingly, none of the nonhepatic organs (n = 10) utilized from these bacteremic donors resulted in transmissions. These cases highlight the fact that risk of transmission from bacteremic donors is not eliminated with antimicrobial therapy in the donor and recipient. As no transmissions occurred in recipients of nonhepatic organs from these donors, these cases also suggest that liver recipients may be at higher risk of donor transmitted bacteremia.