Patients waitlisted for and recipients of solid organ transplants (SOT) are perceived to have a higher risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and death; ...however, definitive epidemiological evidence is lacking. In a comprehensive national cohort study enabled by linkage of the UK transplant registry and Public Health England and NHS Digital Tracing services, we examined the incidence of laboratory‐confirmed SARS‐CoV‐2 infection and subsequent mortality in patients on the active waiting list for a deceased donor SOT and recipients with a functioning SOT as of February 1, 2020 with follow‐up to May 20, 2020. Univariate and multivariable techniques were used to compare differences between groups and to control for case‐mix. One hundred ninety‐seven (3.8%) of the 5184 waitlisted patients and 597 (1.3%) of the 46 789 SOT recipients tested positive for SARS‐CoV‐2. Mortality after testing positive for SARS‐CoV‐2 was 10.2% (20/197) for waitlisted patients and 25.8% (154/597) for SOT recipients. Increasing recipient age was the only variable independently associated with death after positive SARS‐CoV‐2 test. Of the 1004 transplants performed in 2020, 41 (4.1%) recipients have tested positive for SARS‐CoV‐2 with 8 (0.8%) deaths reported by May 20. These data provide evidence to support decisions on the risks and benefits of SOT during the coronavirus disease 2019 pandemic.
The authors link national datasets in England and compare waitlisted patients and transplant recipients on the incidence of SARS‐CoV‐2 infection and subsequent mortality to inform risk/benefit decisions during the COVID‐19 pandemic.
Summary
Donation after circulatory death (DCD) has become an accepted practice in many countries and remains a focus of intense interest in the transplant community. The present study is aimed at ...providing a description of the current situation of DCD in European countries. Specific questionnaires were developed to compile information on DCD practices, activities and post‐transplant outcomes. Thirty‐five countries completed the survey. DCD is practiced in 18 countries: eight have both controlled DCD (cDCD) and uncontrolled DCD (uDCD) programs, 4 only cDCD and 6 only uDCD. All these countries have legally binding and/or nonbinding texts to regulate the practice of DCD. The no‐touch period ranges from 5 to 30 min. There are variations in ante and post mortem interventions used for the practice of cDCD. During 2008–2016, the highest DCD activity was described in the United Kingdom, Spain, Russia, the Netherlands, Belgium and France. Data on post‐transplant outcomes of patients who receive DCD donor kidneys show better results with grafts obtained from cDCD versus uDCD donors. In conclusion, DCD is becoming increasingly accepted and performed in Europe, importantly contributing to the number of organs available and providing acceptable post‐transplantation outcomes.
There is international variability in the determination of death. Death in donation after circulatory death (DCD) can be defined by the permanent cessation of brain circulation. Post‐mortem ...interventions that restore brain perfusion should be prohibited as they invalidate the diagnosis of death. Retrieval teams should develop protocols that ensure the continued absence of brain perfusion during DCD organ recovery. In situ normothermic regional perfusion (NRP) or restarting the heart in the donor's body may interrupt the permanent cessation of brain perfusion because, theoretically, collateral circulations may restore it. We propose refinements to current protocols to monitor and exclude brain reperfusion during in situ NRP. In abdominal NRP, complete occlusion of the descending aorta prevents brain perfusion in most cases. Inserting a cannula in the ascending aorta identifies inadequate occlusion of the descending aorta or any collateral flow and diverts flow away from the brain. In thoracoabdominal NRP opening the aortic arch vessels to atmosphere allows collateral flow to be diverted away from the brain, maintaining the permanence standard for death and respecting the dead donor rule. We propose that these hypotheses are correct when using techniques that simultaneously occlude the descending aorta and open the aortic arch vessels to atmosphere.
The authors present techniques to prevent the restoration of brain perfusion during in situ normothermic regional perfusion by ensuring the diversion of any possible collateral supply.
International resurgence in the donation of organs after circulatory death (DCD) - seven major ethical, legal and professional guidances have been published in the UK relating to deceased donation ...and DCD since 2008 - professional framework that underpins the DCD programme in the UK is the strongest in the world.
The diagnosis of death using neurological criteria (brain death) has profound social, legal and ethical implications. The diagnosis can be made using standard clinical tests examining for brain ...function, but in some patient populations and in some countries additional tests may be required. Computed tomography (CT) angiography, which is currently in wide clinical use, has been identified as one such test.
To assess from the current literature the sensitivity of CT cerebral angiography as an additional confirmatory test for diagnosing death using neurological criteria, following satisfaction of clinical neurological criteria for brain death.
We performed comprehensive literature searches to identify studies that would assess the diagnostic accuracy of CT angiography (the index test) in cohorts of adult patients, using the diagnosis of brain death according to neurological criteria as the target condition. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5) and the following databases from January 1992 to August 2012: MEDLINE; EMBASE; BNI; CINAHL; ISI Web of Science; BioMed Central. We also conducted searches in regional electronic bibliographic databases and subject-specific databases (MEDION; IndMed; African Index Medicus). A search was also conducted in Google Scholar where we reviewed the first 100 results only. We handsearched reference lists and conference proceedings to identify primary studies and review articles. Abstracts were identified by two authors. Methodological assessment of studies using the QUADAS-2 tool and further data extraction for re-analysis were performed by three authors.
We included in this review all large case series and cohort studies that compared the results of CT angiography with the diagnosis of brain death according to neurological criteria. Uniquely, the reference standard was the same as the target condition in this review.
We reviewed all included studies for methodological quality according to the QUADAS-2 criteria. We encountered significant heterogeneity in methods used to interpret CT angiography studies and therefore, where possible, we re-analysed the published data to conform to a standard radiological interpretation model. The majority of studies (with one exception) were not designed to include patients who were not brain dead, and therefore overall specificity was not estimable as part of a meta-analysis. Sensitivity, confidence and prediction intervals were calculated for both as-published data and as re-analysed to a standardized interpretation model.
Ten studies were found including 366 patients in total. We included eight studies in the as-published data analysis, comprising 337 patients . The methodological quality of the studies was overall satisfactory, however there was potential for introduction of significant bias in several specific areas relating to performance of the index test and to the timing of index versus reference tests. Results demonstrated a sensitivity estimate of 0.84 (95% confidence interval (CI) 0.69 to 0.93). The 95% approximate prediction interval was very wide (0.34 to 0.98). Data in three studies were available as a four-vessel interpretation model and the data could be re-analysed to a four-vessel interpretation model in a further five studies, comprising 314 patient events. Results demonstrated a similar sensitivity estimate of 0.85 (95% CI 0.77 to 0.91) but with an improved 95% approximate prediction interval (0.56 to 0.96).
The available evidence cannot support the use of CT angiography as a mandatory test, or as a complete replacement for neurological testing, in the management pathway of patients who are suspected to be clinically brain dead. CT angiography may be useful as a confirmatory or add-on test following a clinical diagnosis of death, assuming that clinicians are aware of the relatively low overall sensitivity. Consensus on a standard radiological interpretation protocol for future published studies would facilitate further meta-analysis.
Abstract Background The availability of extracorporeal membrane oxygenation (ECMO) assisted cardiopulmonary resuscitation (E-CPR), for use in refractory out-of hospital cardiac arrest (OHCA), is ...increasing. In parallel, some countries have developed uncontrolled donation after circulatory determination of death (uDCDD) programs using ECMO to preserve organs for transplantation purposes. Aim When facing a refractory OHCA, how does the medical team choose between initiating ECMO as part of an E-CPR protocol or ECMO as part of a uDCDD protocol? Methods To answer these questions we conducted a literature review on E-CPR compared to uDCDD protocols using ECMO and analyzed the raised ethical issues. Results Our analysis reveals that the inclusion criteria in E-CPR and uDCDD protocols are similar. There may be a non-negligible risk of including patients in a uDCDD protocol, when the patient might have been saved by the use of E-CPR. Conclusion In order to avoid the fatal error of letting a saveable patient die, safeguards are necessary. We recommend: (1) the development of internationally accepted termination of resuscitation guidelines that would have to be satisfied prior to inclusion of patients in any uDCDD protocol, (2) the choice regarding modalities of ongoing resuscitation during transfer should be focused on the primary priority of attempting to save the life of patients, (3) only centers of excellence in life-saving resuscitation should initiate or maintain uDCDD programs, (4) E-CPR should be clinically considered first before the initiation of any uDCDD protocol, and (5) there should be no discrimination in the availability of access to E-CPR.
Technological advances, particularly in the capacity to support, replace or transplant failing organs, continue to challenge and refine our understanding of human death. Given the ability to ...reanimate organs before and after death, both inside and outside of the body, through reinstitution of oxygenated circulation, concepts related to death of organs (e.g. cardiac death) are no longer valid. This paper advances the rationale for a single conceptual determination of death related to permanent brain arrest, resulting from primary brain injury or secondary to circulatory arrest. The clinical characteristics of brain arrest are the permanent loss of capacity for consciousness and loss of all brainstem functions. In the setting of circulatory arrest, death occurs after the arrest of circulation to the brain rather than death of the heart. Correspondingly, any intervention that resumes oxygenated circulation to the brain after circulatory arrest would invalidate the determination of death.
The 'Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration In Cardiac Arrest' (PARAMEDIC2) trial showed that adrenaline improves overall survival, but ...not neurological outcomes. We sought to determine the within-trial and lifetime health and social care costs and benefits associated with adrenaline, including secondary benefits from organ donation.
We estimated the costs, benefits (quality-adjusted life years (QALYs)) and incremental cost-effectiveness ratios (ICERs) associated with adrenaline during the 6-month trial follow-up. Model-based analyses explored how results altered when the time horizon was extended beyond 6 months and the scope extended to include recipients of donated organs.
The within-trial (6 months) and lifetime horizon economic evaluations focussed on the trial population produced ICERs of £1,693,003 (€1,946,953) and £81,070 (€93,231) per QALY gained in 2017 prices, respectively, reflecting significantly higher mean costs and only marginally higher mean QALYs in the adrenaline group. The probability that adrenaline is cost-effective was less than 1% across a range of cost-effectiveness thresholds. Combined direct economic effects over the lifetimes of survivors and indirect economic effects in organ recipients produced an ICER of £16,086 (€18,499) per QALY gained for adrenaline with the probability that adrenaline is cost-effective increasing to 90% at a £30,000 (€34,500) per QALY cost-effectiveness threshold.
Adrenaline was not cost-effective when only directly related costs and consequences are considered. However, incorporating the indirect economic effects associated with transplanted organs substantially alters cost-effectiveness, suggesting decision-makers should consider the complexity of direct and indirect economic impacts of adrenaline.
ISRCTN73485024 . Registered on 13 March 2014.
There are inequalities experienced by minority ethnic groups in the UK in organ donation and transplant services, with significant variation in relation to demand for, access to and waiting times for ...these services.
A narrative review of research obtained via several databases, including PubMed and Medline, was conducted.
A vision of equity and inclusion, which meets the need of the heterogeneous UK population, can only be realized by adopting a culturally competent approach to systems-wide working in organ donation in four core areas-transplant services; workforce and staff training; diversity and inclusion research; and public engagement.
Most of the data on the background of organ donors and recipients use general categories such as Asian or Black. We need to progress to a position of more granular data by more specific ethnicity so that we can better understand the trends and target action accordingly.
By positively embracing the heterogeneity of the UK population, demand for transplantation can be reduced through a sustained commitment to public health interventions and culturally competent approaches in the management of long-term conditions.
Improved access to transplantation and reduced waiting times can be achieved to increase the number of organ donors from minority ethnic groups if there are concerted and adequately resourced culturally competent interventions with concomitant evaluation programmes.
PDF
