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Purpose To provide a practical overview of the management of the potential organ donor in the intensive care unit. Methods Seven areas of donor management were considered for this review: hemodynamic management; fluids and electrolytes; respiratory management; endocrine management; temperature management; anaemia and coagulation; infection management. For each subchapter, a narrative review was conducted. Results and conclusions Most elements in the current recommendations and guidelines are based on pathophysiological reasoning, epidemiological observations, or extrapolations from general ICU management strategies, and not on evidence from randomized controlled trials. The cardiorespiratory management of brain-dead donors is very similar to the management of critically ill patients, and the same applies to the management of anaemia and coagulation. Central diabetes insipidus is of particular concern, and should be diagnosed based on clinical criteria. Depending on the degree of vasopressor dependency, it can be treated with intermittent desmopressin or continuous vasopressin, intravenously. Temperature management of the donor is an area of uncertainty, but it appears reasonable to strive for a core temperature of > 35 °C. The indications and controversies regarding endocrine therapies, in particular thyroid hormone replacement therapy, and corticosteroid therapy, are discussed. The potential donor should be assessed clinically for infections, and screening tests for specific infections are an essential part of donor management. Although the rate of infection transmission from donor to receptor is low, certain infections are still a formal contraindication to organ donation. However, new antiviral drugs and strategies now allow organ donation from certain infected donors to be done safely.

Hypothermic oxygenated machine perfusion (HOPE) was recently tested in preclinical trials in kidney transplantation (KT). Here we investigate the effects of HOPE on extended-criteria-donation (ECD) kidney allografts (KA). Fifteen ECD-KA were submitted to 152 ± 92 min of end-ischemic HOPE and were compared to a matched group undergoing conventional-cold-storage (CCS) KT (n = 30). Primary (delayed graft function-DGF) and secondary (e.g. postoperative complications, perfusion parameters) endpoints were analyzed within 6-months follow-up. There was no difference in the development of DGF between the HOPE and CCS groups (53% vs. 33%, respectively; p = 0.197). Serum urea was lower following HOPE compared to CCS (p = 0.003), whereas the CCS group displayed lower serum creatinine and higher eGFR rates on postoperative days (POD) 7 and 14. The relative decrease of renal vascular resistance (RR) following HOPE showed a significant inverse association with serum creatinine on POD1 (r = − 0.682; p = 0.006) as well as with serum urea and eGFR. Besides, the relative RR decrease was more prominent in KA with primary function when compared to KA with DGF (p = 0.013). Here we provide clinical evidence on HOPE in ECD-KT after brain death donation. Relative RR may be a useful predictive marker for KA function. Further validation in randomized controlled trials is warranted. Trial registration: clinicaltrials.gov (NCT03378817, Date of first registration: 20/12/2017).

This report describes transplantation of hearts from three infant donors (mean age at donation, 3.7 days) who had died from cardiocirculatory causes. The recipients (mean age, 2.2 months) all survived to 6 months with excellent left ventricular function. This approach to transplantation has been controversial but offers the prospect of expanding the donor pool. This report describes transplantation of hearts from three infant donors who had died from cardiocirculatory causes. The recipients all survived to 6 months with excellent left ventricular function. This controversial approach offers the prospect of expanding the donor pool. Pediatric heart transplantation after the declaration of brain death in donors has been performed for more than 25 years in more than 6000 recipients. 1 The first successful heart-transplant procedure in an infant was reported 20 years ago, and decades-long survival has been reported. 1 , 2 The average survival for children who are alive 1 year after transplantation is more than 15 years and exceeds that of adults. 3 However, the risk of death while awaiting a donor is highest for children awaiting a cardiac transplant. 4 Infant heart-transplant recipients face up to a 25% waiting-list mortality, which is an order of magnitude higher . . .

Background The major concern in liver transplantation of grafts from donation after circulatory death (DCD) donors remains the high incidence of non-anastomotic biliary strictures (NAS). Machine perfusion has been proposed as an alternative strategy for organ preservation which reduces ischemia-reperfusion injury (IRI). Experimental studies have shown that dual hypothermic oxygenated machine perfusion (DHOPE) is associated with less IRI, improved hepatocellular function, and better preserved mitochondrial and endothelial function compared to conventional static cold storage (SCS). Moreover, DHOPE was safely applied with promising results in a recently performed phase-1 study. The aim of the current study is to determine the efficacy of DHOPE in reducing the incidence of NAS after DCD liver transplantation. Methods This is an international multicenter randomized controlled trial. Adult patients (≥18 yrs. old) undergoing transplantation of a DCD donor liver (Maastricht category III) will be randomized between the intervention and control group. In the intervention group, livers will be subjected to two hours of end-ischemic DHOPE after SCS and before implantation. In the control group, livers will be subjected to care as usual with conventional SCS only. Primary outcome is the incidence of symptomatic NAS diagnosed by a blinded adjudication committee. In all patients, magnetic resonance cholangiography will be obtained at six months after transplantation. Discussion DHOPE is associated with reduced IRI of the bile ducts. Whether reduced IRI of the bile ducts leads to lower incidence of NAS after DCD liver transplantation can only be examined in a randomized controlled trial. Trial registration The trial was registered in Clinicaltrials.gov in September 2015 with the identifier NCT02584283 .

BACKGROUNDLow organ donation rates remain a major barrier to organ transplantation.OBJECTIVEWe aimed to determine the effect of a video and patient cueing on organ donation consent among patients meeting with their primary care provider.DESIGNThis was a randomized controlled trial between February 2013 and May 2014.SETTINGThe waiting rooms of 18 primary care clinics of a medical system in Cuyahoga County, Ohio.PATIENTSThe study included 915 patients over 15.5 years of age who had not previously consented to organ donation.INTERVENTIONSJust prior to their clinical encounter, intervention patients (n = 456) watched a 5-minute organ donation video on iPads and then choose a question regarding organ donation to ask their provider. Control patients (n = 459) visited their provider per usual routine.MAIN MEASURESThe primary outcome was the proportion of patients who consented for organ donation. Secondary outcomes included the proportion of patients who discussed organ donation with their provider and the proportion who were satisfied with the time spent with their provider during the clinical encounter.KEY RESULTSIntervention patients were more likely than control patients to consent to donate organs (22 % vs. 15 %, OR 1.50, 95%CI 1.10–2.13). Intervention patients were also more likely to have donation discussions with their provider (77 % vs. 18 %, OR 15.1, 95%CI 11.1–20.6). Intervention and control patients were similarly satisfied with the time they spent with their provider (83 % vs. 86 %, OR 0.87, 95%CI 0.61–1.25).LIMITATIONHow the observed increases in organ donation consent might translate into a greater organ supply is unclear.CONCLUSIONWatching a brief video regarding organ donation and being cued to ask a primary care provider a question about donation resulted in more organ donation discussions and an increase in organ donation consent. Satisfaction with the time spent during the clinical encounter was not affected.TRIAL REGISTRATIONclinicaltrials.gov Identifier: NCT01697137

The continuing shortage of deceased donor organs for transplantation, and the limited number of potential donors after brain death, has led to a resurgence of interest in donation after circulatory death (DCD). The processes of warm and cold ischemia threaten the viability of DCD organs, but these can be minimized by well-organized DCD pathways and new techniques of in situ organ preservation and ex situ resuscitation and repair post-explantation. Transplantation survival after DCD is comparable to donation after brain death despite higher rates of primary non-function and delayed graft function. Countries with successfully implemented DCD programs have achieved this primarily through the establishment of national ethical, professional and legal frameworks to address both public and professional concerns with all aspects of the DCD pathway. It is unlikely that expanding standard DCD programs will, in isolation, be sufficient to address the worldwide shortage of donor organs for transplantation. It is therefore likely that reliance on extended criteria donors will increase, with the attendant imperative to minimize ischemic injury to candidate organs. Normothermic regional perfusion and ex situ perfusion techniques allow enhanced preservation, assessment, resuscitation and/or repair of damaged organs as a way of improving overall organ quality and preventing the unnecessary discarding of DCD organs. This review will outline exemplar controlled and uncontrolled DCD pathways, highlighting practical and logistical considerations that minimize warm and cold ischemia times while addressing potential ethical concerns. Future perspectives will also be discussed.

The use of kidneys from controlled donation after circulatory death (DCD) donors has the potential to markedly increase kidney transplants performed. However, this potential is not being realized because of concerns that DCD kidneys are inferior to those from donation after brain-death (DBD) donors. The United Kingdom has developed a large and successful controlled DCD kidney transplant program that has allowed for a substantial increase in kidney transplant numbers. Here we describe recent trends in DCD kidney donor activity in the United Kingdom, outline aspects of the donation process, and describe donor selection and allocation of DCD kidneys. Previous UK Transplant Registry analyses have shown that while DCD kidneys are more susceptible to cold ischemic injury and have a higher incidence of delayed graft function, short- and medium-term transplant outcomes are similar in recipients of kidneys from DCD and DBD donors. We present an updated, extended UK registry analysis showing that longer-term transplant outcomes in DCD donor kidneys are also similar to those for DBD donor kidneys, and that transplant outcomes for kidneys from expanded-criteria DCD donors are no less favorable than for expanded-criteria DBD donors. Accordingly, the selection criteria for use of kidneys from DCD donors should be the same as those used for DBD donors. The UK experience suggests that wider international development of DCD kidney transplantation programs will help address the global shortage of deceased donor kidneys for transplantation.

We sought to build prediction models for organ transplantation and recipient survival using both biomarkers and clinical information. We abstracted clinical variables from a previous randomized trial (n = 556) of donor management. In a subset of donors (n = 97), we measured two candidate biomarkers in plasma at enrollment and just prior to explantation. Secretory leukocyte protease inhibitor (SLPI) was significant for predicting liver transplantation (C-statistic 0.65 (0.53, 0.78)). SLPI also significantly improved the predictive performance of a clinical model for liver transplantation (integrated discrimination improvement (IDI): 0.090 (0.009, 0.210)). For other organs, clinical variables alone had strong predictive ability (C-statistic >0.80). Recipient 3-years survival was 80.0% (71.9%, 87.0%). Donor IL-6 was significantly associated with recipient 3-years survival (adjusted Hazard Ratio (95%CI): 1.26(1.08, 1.48), P = .004). Neither clinical variables nor biomarkers showed strong predictive ability for 3-year recipient survival. Plasma biomarkers in neurologically deceased donors were associated with organ use. SLPI enhanced prediction within a liver transplantation model, whereas IL-6 before transplantation was significantly associated with recipient 3-year survival. Clinicaltrials.gov: NCT00987714. •Selection criteria for organs from neurologically deceased donors are imperfect.•SLPI was significant for predicting liver transplantation.•SLPI also improved prediction of a clinical model for liver transplantation.•Clinical variables alone had strong predictive ability for other organs.•Donor IL-6 was significantly associated with recipient 3-years survival.•Neither clinical variables nor biomarkers had strong prediction for 3-yr survival.

Background The quality of clinical care of brain-dead potential organ donors may help reduce donor losses caused by irreversible or unreversed cardiac arrest and increase the number of organs donated. We sought to determine whether an evidence-based, goal-directed checklist for donor management in intensive care units (ICUs) can reduce donor losses to cardiac arrest. Methods/design The DONORS study is a multicentre, cluster-randomised controlled trial with a 1:1 allocation ratio designed to compare an intervention group (goal-directed checklist for brain-dead potential organ donor management) with a control group (standard ICU care). The primary outcome is loss of potential donors due to cardiac arrest. Secondary outcomes are the number of actual organ donors and the number of solid organs recovered per actual donor. Exploratory outcomes include the achievement of relevant clinical goals during the management of brain-dead potential organ donors. The present statistical analysis plan (SAP) describes all primary statistical procedures that will be used to evaluate the results and perform exploratory and sensitivity analyses of the trial. Discussion The SAP of the DONORS study aims to describe its analytic procedures, enhancing the transparency of the study. At the moment of SAP subsmission, 63 institutions have been randomised and were enrolling study participants. Thus, the analyses reported herein have been defined before the end of the study recruitment and database locking. Trial registration ClinicalTrials.gov, NCT03179020 . Registered on 7 June 2017.

Orthotopic heart transplantation is the gold-standard long-term treatment for medically refractive end-stage heart failure. However, suitable cardiac donors are scarce. Although donation after circulatory death has been used for kidney, liver, and lung transplantation, it is not used for heart transplantation. We report a case series of heart transplantations from donors after circulatory death. The recipients were patients at St Vincent's Hospital, Sydney, Australia. They received Maastricht category III controlled hearts donated after circulatory death from people younger than 40 years and with a maximum warm ischaemic time of 30 min. We retrieved four hearts through initial myocardial protection with supplemented cardioplegia and transferred to an Organ Care System (Transmedics) for preservation, resuscitation, and transportation to the recipient hospital. Three recipients (two men, one woman; mean age 52 years) with low transpulmonary gradients (<8 mm Hg) and without previous cardiac surgery received the transplants. Donor heart warm ischaemic times were 28 min, 25 min, and 22 min, with ex-vivo Organ Care System perfusion times of 257 min, 260 min, and 245 min. Arteriovenous lactate values at the start of perfusion were 8·3–8·1 mmol/L for patient 1, 6·79–6·48 mmol/L for patient 2, and 7·6–7·4 mmol/L for patient 3. End of perfusion lactate values were 3·6–3·6 mmol/L, 2·8–2·3 mmol/L, and 2·69–2·54 mmol/L, respectively, showing favourable lactate uptake. Two patients needed temporary mechanical support. All three recipients had normal cardiac function within a week of transplantation and are making a good recovery at 176, 91, and 77 days after transplantation. Strict limitations on donor eligibility, optimised myocardial protection, and use of a portable ex-vivo organ perfusion platform can enable successful, distantly procured orthotopic transplantation of hearts donated after circulatory death. NHMRC, John T Reid Charitable Trust, EVOS Trust Fund, Harry Windsor Trust Fund.