Beyond the Concepts of Elder and Marginal in DCD Liver Transplantation: A Prospective Observational Matched-Cohort Study in the Italian Clinical Setting.

Donation after circulatory determination of death (DCD) is a valuable strategy to increase the availability of grafts for liver transplantation (LT). As the average age of populations rises, the donor pool is likely to be affected by a potential increase in DCD donor age in the near future. We conducted a prospective cohort study to evaluate post-transplantation outcomes in recipients of grafts from elderly DCD donors compared with younger DCD donors, and elderly donors after brainstem determination of death (DBD). From August 2020 to May 2022, consecutive recipients of deceased donor liver-only transplants were enrolled in the study. DCD recipients were propensity score matched 1:3 to DBD recipients. One-hundred fifty-seven patients were included, 26 of whom (16.6%) were transplanted with a DCD liver graft. After propensity score matching and stratification, three groups were obtained: 15 recipients of DCD donors ≥75 years, 11 recipients of DCD donors <75 years, and 28 recipients of DBD donors ≥75 years. Short-term outcomes, as well as 12 months graft survival rates (93.3%, 100%, and 89.3% respectively), were comparable among the groups. LT involving grafts retrieved from very elderly DCD donors was feasible and safe in an experienced high-volume center, with outcomes comparable to LTs from younger DCD donors and age-matched DBD donors.

What does "brainstem death" mean? A review of international protocols.

PURPOSE: The term "brainstem death" is ambiguous; it can be used to refer either exclusively to loss of function of the brainstem or loss of function of the whole brain. We aimed to establish the term's intended meaning in national protocols for the determination of brain death/death by neurologic criteria (BD/DNC) from around the world. METHODS: Of 78 unique international protocols on determination of BD/DNC, we identified eight that referred exclusively to loss of function of the brainstem in the definition of death. Each protocol was reviewed to ascertain whether it 1) required assessment for loss of function of the whole brain, 2) required assessment only for loss of function of the brainstem, or 3) was ambiguous about whether loss of function of the higher brain was required to declare DNC. RESULTS: Of the eight protocols, two (25%) required assessment for loss of function of the whole brain, three (37.5%) only required assessment for loss of function of the brainstem, and three (37.5%) were ambiguous about whether loss of function of the higher brain was required to declare death. The overall agreement between raters was 94% (κ = 0.91). CONCLUSIONS: There is international variability in the intended meaning of the terms "brainstem death" and "whole brain death" resulting in ambiguity and potentially inaccurate or inconsistent diagnosis. Regardless of the nomenclature, we advocate for national protocols to be clear regarding any requirement for ancillary testing in cases of primary infratentorial brain injury who may fulfill clinical criteria for BD/DNC.

RéSUMé: OBJECTIF: Le terme « mort du tronc cérébral ¼ est ambigu; il peut être utilisé pour désigner soit la perte de fonction du tronc cérébral uniquement, soit la perte de fonction du cerveau entier. Nous avons cherché à établir la signification voulue du terme dans les protocoles nationaux utilisés pour la détermination de la mort cérébrale/du décès selon des critères neurologiques (MC/DCN) du monde entier. MéTHODE: Sur 78 protocoles internationaux uniques sur la détermination de la MC/DCN, nous en avons identifié huit qui faisaient exclusivement référence à la perte de fonction du tronc cérébral dans la définition de la mort. Chaque protocole a été examiné pour déterminer s'il 1) exigeait une évaluation de la perte de fonction du cerveau entier, 2) exigeait une évaluation uniquement pour la perte de fonction du tronc cérébral, ou 3) était ambigu quant à savoir si la perte de fonction du cerveau supérieur était requise pour déclarer un DCN. RéSULTATS: Sur les huit protocoles, deux (25 %) exigeaient une évaluation de la perte de fonction de l'ensemble du cerveau, trois (37,5 %) ne nécessitaient qu'une évaluation de la perte de fonction du tronc cérébral, et trois (37,5 %) étaient ambigus quant à savoir si la perte de fonction du cerveau supérieur était nécessaire pour déclarer le décès. L'accord global entre les évaluateurs était de 94 %, (κ = 0,91). CONCLUSION: Il existe une variabilité internationale quant au sens voulu des termes « mort du tronc cérébral ¼ et « mort cérébrale totale ¼ qui entraîne une ambiguïté et un diagnostic potentiellement inexact ou incohérent. Quelle que soit la nomenclature, nous préconisons que les protocoles nationaux soient clairs en ce qui concerne toute exigence d'examens auxiliaires dans les cas de lésion cérébrale infratentorielle primaire qui pourraient répondre aux critères cliniques de MC/DCN.

Infratentorial brain injury and death by neurologic criteria in Canada: a narrative review.

There are two anatomic formulations of death by neurologic criteria accepted worldwide: whole-brain death and brainstem death. As part of the Canadian Death Definition and Determination Project, we convened an expert working group and performed a narrative review of the literature. Infratentorial brain injury (IBI) with an unconfounded clinical assessment consistent with death by neurologic criteria represents a nonrecoverable injury. The clinical determination of death cannot distinguish between IBI and whole-brain cessation of function. Current clinical, functional, and neuroimaging assessments cannot reliably confirm the complete and permanent destruction of the brainstem. No patient with isolated brainstem death has been reported to recover consciousness and all patients have died. Studies suggest a significant majority of isolated brainstem death will evolve into whole-brain death, influenced by time/duration of somatic support and impacted by ventricular drainage and/or posterior fossa decompressive craniectomy. Acknowledging variability in intensive care unit (ICU) physician opinion on this matter, a majority of Canadian ICU physicians would perform ancillary testing for death determination by neurologic criteria in the context of IBI. There is currently no reliable ancillary test to confirm complete destruction of the brainstem; ancillary testing currently includes evaluation of both infratentorial and supratentorial flow. Acknowledging international variability in this regard, the existing evidence reviewed does not provide sufficient confidence that the clinical exam in IBI represents a complete and permanent destruction of the reticular activating system and thus the capacity for consciousness. On this basis, IBI consistent with clinical signs of death by neurologic criteria without significant supratentorial involvement does not fulfill criteria for death in Canada and ancillary testing is required.

RéSUMé: Il existe deux formulations anatomiques du décès selon des critères neurologiques acceptés dans le monde entier : la mort du cerveau entier et la mort du tronc cérébral. Dans le cadre du Projet canadien de définition et de détermination du décès, nous avons réuni un groupe de travail composé d'experts et réalisé un compte rendu narratif de la littérature. Une lésion cérébrale infratentorielle (LCI) avec une évaluation clinique sans facteur confondant et compatible avec un décès selon des critères neurologiques représente une atteinte irrécupérable. La détermination clinique du décès ne permet pas de faire la distinction entre une LCI et l'arrêt de la fonction dans le cerveau entier. Les évaluations cliniques, fonctionnelles et de neuroimagerie actuelles ne peuvent pas confirmer de manière fiable la destruction complète et permanente du tronc cérébral. La récupération de la conscience n'a jamais été signalée chez aucun patient présentant une mort isolée du tronc cérébral, et tous les patients sont décédés. Des études suggèrent qu'une majorité significative des morts isolées du tronc cérébral évolueront vers la mort cérébrale entière, étant influencées par le temps et la durée de l'assistance somatique et impactées par le drainage ventriculaire et/ou la craniectomie décompressive de la fosse postérieure. Compte tenu de la variabilité des opinions des médecins intensivistes à ce sujet, la majorité des médecins intensivistes canadiens réaliseraient des examens auxiliaires pour déterminer le décès selon des critères neurologiques dans le contexte d'une LCI. Il n'existe actuellement aucun examen auxiliaire fiable pour confirmer la destruction complète du tronc cérébral; les examens auxiliaires comprennent actuellement l'évaluation de la circulation infratentorielle et supratentorielle. Reconnaissant la variabilité internationale à cet égard, les données probantes existantes passées en revue ne sont pas suffisamment fiables pour affirmer que l'examen clinique en cas de LCI représente une destruction complète et permanente du système d'activation réticulaire et donc de la capacité de conscience. En se fondant sur cette base, une LCI compatible avec les signes cliniques d'un décès selon des critères neurologiques sans atteinte supratentorielle significative ne répond pas aux critères de décès au Canada et un examen auxiliaire est requis.

A New Defense of Brain Death as the Death of the Human Organism.

This paper provides a new rationale for equating brain death with the death of the human organism, in light of well-known criticisms made by Alan D Shewmon, Franklin Miller and Robert Truog and a number of other writers. We claim that these criticisms can be answered, but only if we accept that we have slightly redefined the concept of death when equating brain death with death simpliciter. Accordingly, much of the paper defends the legitimacy of redefining death against objections, before turning to the specific task of defending a new rationale for equating brain death with death as slightly redefined.

Admission Perfusion CT for Classifying Early In-Hospital Mortality of Patients With Severe Traumatic Brain Injury: A Pilot Study.

OBJECTIVE. The purposes of this study were to assess the feasibility and safety of perfusion CT of patients with severe traumatic brain injury (TBI) at hospital admission and to examine whether early in-hospital mortality could be characterized with perfusion CT (PCT). The hypothesis was that PCT can be used to characterize brain death, when present, in patients with severe TBI at hospital admission. SUBJECTS AND METHODS. In this prospective cohort pilot study, PCT was performed on patients with severe TBI at first imaging workup at hospital admission. PCT images were processed at the end of the study and assessed for features of brain death. The PCT features were then compared with the clinical outcome of in-hospital mortality. RESULTS. A total of 19 patients (13 men [68.4%]; six women [31.6%]; mean age, 36.4 years; median, 27.5 years) had a mean hospital stay longer than 1 month. No complications of PCT were found. In the first 48 hours after admission, four patients (21%) died. Admission PCT changes suggesting brainstem death were sensitive (75%) and specific (100%) and had high positive (100%) and negative (93.75%) predictive value for correct classification early in-hospital mortality. CONCLUSION. Admission PCT of patients with severe TBI was feasible and safe. Admission PCT findings helped in correctly classifying early in-hospital mortality in the first 48 hours of hospital admission.

Increase in Cadaver Organ Donation Rate at a Tertiary Care Hospital: 23 Years of Experience.

BACKGROUND: Transplantation of Human Organ Act was passed in India in 1994 to streamline organ donation and transplantation activities. It is time to retrospect ourselves and analyze the method to increase organ donation. TYPE OF STUDY: Retrospective observational analysis. OBJECTIVES: To evaluate the change in organ donation rate and reasons for changes in rates. SUBJECTS: Brainstem dead declared patients whose family consented for organ donations in the last 23 years (1997-2019) at Ruby Hall Clinic, Pune, India. MATERIALS AND METHODS: Retrospectively demographic data of the brainstem dead declared donors, the primary diagnoses, comorbidities, and the complete data of their management till organ retrieval was assessed. RESULTS: One hundred cases in the age group 15-75 years (mean 41.6 ± 15.3 years) of brainstem death consented for organ donation were retrospectively studied. The period was divided into two groups, group I and group II included study duration from 1997 to 2013 and from 2013 to 2019 respectively. During the entire period, though the major cause of donor death remained road traffic accidents (RTA) in both the groups (84.21% till 2013 vs 48.15% after 2013), the proportion of donors declared brain dead due to RTA dipped significantly after 2013 (p = 0.004) and the non-RTA causes of brain dead contributed more than RTA causes (51.85% non-RTA vs 48.15% RTA). The major contributor among non-RTA causes was intracranial bleeds (5.26% before 2013 vs 33.33% after 2013, p = 0.014). Compared to the previous 17 years (from 1997) there were more than fourfold rise in the rate of transplantation in the last 6 years (2014-2019) at our institute. Kidneys were retrieved from 90% donors followed by cornea 84%, liver 65%, heart 22%, skin 7%, lungs 6%, and pancreas 5%. CONCLUSION: We have observed that the cadaveric organ donation rate significantly improved after 2013. Reasons might be widening of the donor pool by the selection of more of non-RTA brain death donors over RTA, acceptability of elderly population donor (>60 years) by our transplant teams, early identification of potential organ donor, and better protocol-based management of the cadaver organ donor. HOW TO CITE THIS ARTICLE: Zirpe KG, Suryawanshi P, Gurav S, Deshmukh A, Pote P, Tungenwar A, et al. Increase in Cadaver Organ Donation Rate at a Tertiary Care Hospital: 23 Years of Experience. Indian J Crit Care Med 2020;24(9):804-808.

Survival advantage for patients accepting the offer of a circulatory death liver transplant.

BACKGROUND & AIMS: Donation after circulatory death (DCD) in the UK has tripled in the last decade. However, outcomes following DCD liver transplantation are worse than for donation after brainstem death (DBD) liver transplants. This study examines whether a recipient should accept a "poorer quality" DCD organ or wait longer for a "better" DBD organ. METHODS: Data were collected on 5,825 patients who were registered on the elective waiting list for a first adult liver-only transplant and 3,949 patients who received a liver-only transplant in the UK between 1 January 2008 and 31 December 2015. Survival following deceased donor liver transplantation performed between 2008 and 2015 was compared by Cox regression modelling to assess the impact on patient survival of accepting a DCD liver compared to deferring for a potential DBD transplant. RESULTS: A total of 953 (23%) of the 3,949 liver transplantations performed utilised DCD donors. Five-year post-transplant survival was worse following DCD than DBD transplantation (69.1% [DCD] vs. 78.3% [DBD]; p <0.0001: adjusted hazard ratio [HR] 1.65; 95% CI 1.40-1.94). Of the 5,798 patients registered on the transplant list, 1,325 (23%) died or were removed from the list without receiving a transplant. Patients who received DCD livers had a lower risk-adjusted hazard of death than those who remained on the waiting list for a potential DBD organ (adjusted HR 0.55; 95% CI 0.47-0.65). The greatest survival benefit was in those with the most advanced liver disease (adjusted HR 0.19; 95% CI 0.07-0.50). CONCLUSIONS: Although DCD liver transplantation leads to worse transplant outcomes than DBD transplantation, the individual's survival is enhanced by accepting a DCD offer, particularly for patients with more severe liver disease. DCD liver transplantation improves overall survival for UK listed patients and should be encouraged. LAY SUMMARY: This study looks at patients who require a liver transplant to save their lives; this liver can be donated by a person who has died either after their heart has stopped (donation after cardiac death [DCD]) or after the brain has been injured and can no longer support life (donation after brainstem death [DBD]). We know that livers donated after brainstem death function better than those after cardiac death, but there are not enough of these livers for everyone, so we wished to help patients decide whether it was better for them to accept an early offer of a DCD liver than waiting longer to receive a "better" liver from a DBD donor. We found that patients were more likely to survive if they accepted the offer of a liver transplant as soon as possible (DCD or DBD), especially if their liver disease was very severe.

Redefining Death: Urgent Need to Evolve toward a Homogeneous Definition of Death in India.

The interdependent circulatory-respiratory criteria and brainstem criteria are used to define death. Continuing life-support in brainstem dead patients is a legal conundrum for the health-care professionals and an ethical worry for the society at large. There is an urgent need to revisit this subject to evolve a more uniform definition of death irrespective of the circumstances. A compelling take-home message from this discussion is to spread awareness about brainstem death amongst healthcare professionals. HOW TO CITE THIS ARTICLE: Vadi S, Shroff S. Redefining Death: Urgent Need to Evolve Toward a Homogeneous Definition of Death in India. Indian J Crit Care Med 2019;23(8):368-370.

Re A (A Child) and the United Kingdom Code of Practice for the Diagnosis and Confirmation of Death: Should a Secular Construct of Death Override Religious Values in a Pluralistic Society?

The determination of death by neurological criteria remains controversial scientifically, culturally, and legally, worldwide. In the United Kingdom, although the determination of death by neurological criteria is not legally codified, the Code of Practice of the Academy of Medical Royal Colleges is customarily used for neurological (brainstem) death determination and treatment withdrawal. Unlike some states in the US, however, there are no provisions under the law requiring accommodation of and respect for residents' religious rights and commitments when secular conceptions of death based on medical codes and practices conflict with a traditional concept well-grounded in religious and cultural values and practices. In this article, we analyse the medical, ethical, and legal issues that were generated by the recent judgement of the High Court of England and Wales in Re: A (A Child) [2015] EWHC 443 (Fam). Mechanical ventilation was withdrawn in this case despite parental religious objection to a determination of death based on the code of practice. We outline contemporary evidence that has refuted the reliability of tests of brainstem function to ascertain the two conjunctive clinical criteria for the determination of death that are stipulated in the code of practice: irreversible loss of capacity for consciousness and somatic integration of bodily biological functions. We argue that: (1) the tests of brainstem function were not properly undertaken in this case; (2) the two conjunctive clinical criteria set forth in the code of practice cannot be reliably confirmed by these tests in any event; and (3) absent authentication of the clinical criteria of death, the code of practice (in fact, although implicitly rather than explicitly) wrongly invokes a secular definition of death based on the loss of personhood. Consequently, the moral obligation of a pluralistic society to honor and respect diverse religious convictions to the greatest extent possible is being violated. Re A (A Child) is contrasted with the US case of Jahi McMath in which the court accommodated parental religious objection to the determination of neurological death codified in the Uniform Determination of Death Act. We conclude that the legal system in the United Kingdom should not favour a secular definition of death over a definition of death that is respectful of religious values about the inviolability and sanctity of life. We recommend the legal recognition of religious accommodation in death determination to facilitate cultural sensitivity and compassionate care to patients and families in a pluralistic society.

Primary Posterior Fossa Lesions and Preserved Supratentorial Cerebral Blood Flow: Implications for Brain Death Determination.

BACKGROUND: Patients with primary posterior fossa catastrophic lesions may clinically meet brain death criteria, but may retain supratentorial brain function or blood flow. These patients could be declared brain-dead in the United Kingdom (UK), but not in the United States of America (USA). We report the outcome of adult patients with primary posterior fossa lesions without concurrent major supratentorial injury. METHODS: Henry Ford Hospital database was reviewed over a period of 88 months in order to identify all adult patients with isolated brainstem or posterior fossa lesions. We excluded patients with concurrent significant supratentorial pathology potentially confounding the clinical brain death examination. One more patient from a different hospital meeting these criteria was also included. RESULTS: Three patients out of 161 met inclusion criteria (1.9% of all brain deaths during this period). With the addition of a fourth patient from another hospital, 4 patients were analyzed. All four patients had catastrophic brainstem and cerebellar injuries meeting the clinical criteria of brain death with positive apnea test in the UK. All had preserved supratentorial blood flow, which after a period of 2 h to 6 days disappeared on repeat testing, allowing declaration of brain death by US criteria in all four. One patient became an organ donor. CONCLUSIONS: Patients with primary posterior fossa catastrophic lesions, who clinically seem to be brain-dead, evolve from retaining to losing supratentorial blood flow. If absent cerebral blood flow is used as an additional criterion for the declaration of death by neurological criteria, these patients are not different than those who become brain death due to supratentorial lesions.

Seeing for themselves - healthcare professionals' views about the presence of family members during brainstem death testing.

AIMS AND OBJECTIVES: To provide an insight into the views of healthcare professionals on the presence of family members during brainstem death testing. BACKGROUND: Brainstem death presents families with a paradoxical death that can be difficult to define. International research suggests families should be given the choice to be present at brainstem death testing, yet it appears few units offer families the choice to be present and little attention has been paid to developing practice to enable effective facilitation of choice. DESIGN: A qualitative, exploratory design was adopted to understand the perceptions of healthcare professionals. Individual semi-structured interviews were audio-taped and carried out over two months. METHODS: A purposive sample of 10 nurses and 10 doctors from two tertiary intensive care units in the United Kingdom was interviewed, and transcripts were analysed using content analysis to identify emergent categories and themes. RESULTS: Healthcare professionals indicated different perceptions of death in the context of catastrophic brainstem injury. The majority of participants favoured offering families the choice to be present while acknowledging the influence of organisational culture. Identified benefits included acceptance, closure and better understanding. Suggested challenges involved the assumption of trauma or disruption and sense of obligation for families to accept if choice was offered. Key issues involved improving knowledge and communication skills to individually tailor support for families involved. CONCLUSIONS: If families are to be offered the choice of witnessing brainstem death testing, considering that needs and conventions will differ according to global cultural backgrounds, then key needs must be met to ensure that effective care and support is provided to families and clinicians. RELEVANCE TO CLINICAL PRACTICE: A proactive approach to facilitating family choice to be present at testing requires the development of guidelines that accommodate cultural and professional variations to provide excellence in end-of-life care.

Frequent Preservation of Neurologic Function in Brain Death and Brainstem Death Entails False-Positive Misdiagnosis and Cerebral Perfusion.

Some patients who have been diagnosed as "dead by neurologic criteria" continue to exhibit certain brain functions, most commonly, neuroendocrine functions. This preservation of neurologic function after the diagnosis of "brain death" or "brainstem death" is an ongoing source of controversy and concern in the medical, bioethics, and legal literatures. Most obviously, if some brain function persists, then it is not the case that all functions of the entire brain have ceased and hence, declaring such a patient to be "dead" would be a false positive, in any nation with so-called "whole brain death" laws. Furthermore, and perhaps more concerning, the preservation of any brain function necessarily entails the preservation of some amount of brain perfusion, thereby raising the concern as to whether additional areas of neural tissue may remain viable, including areas in the brainstem. These and other considerations cast significant doubt on the reliability of diagnosing either "brain death" or "brainstem death."

Intrathecal baclofen overdose mimicking brainstem death during deep brain stimulation surgery for pain.

We describe a unique case of intrathecal baclofen overdose mimicking brainstem death, during bilateral anterior cingulate cortex deep brain stimulation (DBS) for pain. A 37-year-old man with chronic regional pain syndrome requiring an intrathecal baclofen pump underwent DBS under general anaesthesia and experienced an intraoperative generalised tonic-clonic seizure on dural opening. Once the operation was completed, the patient was noted to have fixed, dilated pupils bilaterally and was transferred for an emergency computed tomography scan of the head, which did not reveal any acute intracranial pathology. The patient was transferred to the intensive care unit for management of concurrent hypotension, bradycardia and supportive management of his low Glasgow Coma Scale (GCS) score. A trial of atropine to counter the bradycardia was unsuccessful. Intrathecal baclofen toxicity was suspected as a diagnosis of exclusion, necessitating urgent aspiration of the baclofen pump. The patient's GCS score improved after pump aspiration and he was discharged home several days later. It was noted that the intrathecal baclofen pump had been refilled several days previously and the patient had reported intermittent episodes of somnolence. In perioperative patients with intrathecal baclofen pumps in situ, baclofen toxicity should always be considered as a differential in perioperative complications, even if it is considered a rare event.

Brain death: a clinical overview.

Brain death, also commonly referred to as death by neurologic criteria, has been considered a legal definition of death for decades. Its determination involves many considerations and subtleties. In this review, we discuss the philosophy and history of brain death, its clinical determination, and special considerations. We discuss performance of the main clinical components of the brain death exam: assessment of coma, cranial nerves, motor testing, and apnea testing. We also discuss common ancillary tests, including advantages and pitfalls. Special discussion is given to extracorporeal membrane oxygenation, target temperature management, and determination of brain death in pediatric populations. Lastly, we discuss existing controversies and future directions in the field.

Hypothalamic function in patients diagnosed as brain dead and its practical consequences.

Some patients who have been diagnosed as "dead by neurologic criteria" continue to exhibit certain brain functions, most commonly, neuroendocrine functions. In this chapter, we review the pathophysiology of brain death that can lead either to neuroendocrine failure or to preserved neuroendocrine functioning. We review the evidence on continued hypothalamic functioning in patients who have been declared "brain dead," examine potential mechanisms that would explain these findings, and discuss how these findings create additional confounds for brain death testing. We conclude by reviewing the evidence for the management of hypothalamic-pituitary failure in the setting of brain death and organ transplantation.

A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death.

BACKGROUND: Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient. To enable future assessment of novel perfusion technologies in our research program, we thus aimed to develop a clinically relevant sheep model of HTx following 24 h of donor BSD. METHODS: BSD donors (vs. sham neurological injury, 4/group) were hemodynamically supported and monitored for 24 h, followed by heart preservation with cold static storage. Bicaval orthotopic HTx was performed in matched recipients, who were weaned from cardiopulmonary bypass (CPB), and monitored for 6 h. Donor and recipient blood were assayed for inflammatory and cardiac injury markers, and cardiac function was assessed using echocardiography. Repeated measurements between the two different groups during the study observation period were assessed by mixed ANOVA for repeated measures. RESULTS: Brainstem death caused an immediate catecholaminergic hemodynamic response (mean arterial pressure, p = 0.09), systemic inflammation (IL-6 - p = 0.025, IL-8 - p = 0.002) and cardiac injury (cardiac troponin I, p = 0.048), requiring vasopressor support (vasopressor dependency index, VDI, p = 0.023), with normalisation of biomarkers and physiology over 24 h. All hearts were weaned from CPB and monitored for 6 h post-HTx, except one (sham) recipient that died 2 h post-HTx. Hemodynamic (VDI - p = 0.592, heart rate - p = 0.747) and metabolic (blood lactate, p = 0.546) parameters post-HTx were comparable between groups, despite the observed physiological perturbations that occurred during donor BSD. All p values denote interaction among groups and time in the ANOVA for repeated measures. CONCLUSIONS: We have successfully developed an ovine HTx model following 24 h of donor BSD. After 6 h of critical care management post-HTx, there were no differences between groups, despite evident hemodynamic perturbations, systemic inflammation, and cardiac injury observed during donor BSD. This preclinical model provides a platform for critical assessment of injury development pre- and post-HTx, and novel therapeutic evaluation.