Single-centre real-life observational study on mortality and outcomes: decompressive craniectomy and brain death in traumatic brain injury, haemorrhage, and other cerebral diseases.

BACKGROUND: Decompressive hemicraniectomy (DHC) is used after severe brain damages with elevated, refractory intracranial pressure (ICP). In a non age-restricted population, mortality rates and long-term outcomes following DHC are still unclear. This study's objectives were to examine both, as well as to identify predictors of unfavourable outcomes. METHODS: We undertook a retrospective observational analysis of patients aged 18 years and older who underwent DHC at the University Hospital of Bonn between 2018 and 2020, due to traumatic brain injury (TBI), haemorrhage, tumours or infections. Patient outcomes were assessed by conducting telephone interviews, utilising questionnaires for modified Rankin Scale (mRS) and extended Glasgow Outcome scale (GOSE). We evaluated the health-related quality of life using the EuroQol (EQ-5D-5L) scale. RESULTS: A total of 144 patients with a median age of 58.5 years (range: 18 to 85 years) were evaluated. The mortality rate was 67%, with patients passing away at a median of 6.0 days (IQR [1.9-37.6]) after DHC. Favourable outcomes, as assessed by the mRS and GOSE were observed in 10.4% and 6.3% of patients, respectively. Cox regression analysis revealed a 2.0% increase in the mortality risk for every year of age (HR = 1.017; 95% CI [1.01-1.03]; p = 0.004). Uni- and bilateral fixed pupils were associated with a 1.72 (95% CI [1.03-2.87]; p = 0.037) and 3.97 (95% CI [2.44-6.46]; p < 0.001) times higher mortality risk, respectively. ROC-analysis demonstrated that age and pupillary reactivity predicted 6-month mortality with an AUC of 0.77 (95% CI [0.69-0.84]). The only parameter significantly associated with a better quality of life was younger age. CONCLUSIONS: Following DHC, mortality remains substantial, and favourable outcomes occur rarely. Particularly in elderly patients and in the presence of clinical signs of herniation, mortality rates are notably elevated. Hence, the indication for DHC should be set critically.

A ten-year retrospective analysis of decompressive craniectomy or craniotomy after severe brain injury and its implications for donation after brain death.

Craniotomy or decompressive craniectomy are among the therapeutic options to prevent or treat secondary damage after severe brain injury. The choice of procedure depends, among other things, on the type and severity of the initial injury. It remains controversial whether both procedures influence the neurological outcome differently. Thus, estimating the risk of brain herniation and death and consequently potential organ donation remains difficult. All patients at the University Hospital Münster for whom an isolated craniotomy or decompressive craniectomy was performed as a treatment after severe brain injury between 2013 and 2022 were retrospectively included. Proportion of survivors and deceased were evaluated. Deceased were further analyzed regarding anticoagulants, comorbidities, type of brain injury, potential and utilized donation after brain death. 595 patients were identified, 296 patients survived, and 299 deceased. Proportion of decompressive craniectomy was higher than craniotomy in survivors (89% vs. 11%, p < 0.001). Brain death was diagnosed in 12 deceased and 10 donations were utilized. Utilized donations were comparable after both procedures (5% vs. 2%, p = 0.194). Preserved brain stem reflexes as a reason against donation did not differ between decompressive craniectomy or craniotomy (32% vs. 29%, p = 0.470). Patients with severe brain injury were more likely to survive after decompressive craniectomy than craniotomy. Among the deceased, potential and utilized donations did not differ between both procedures. This suggests that brain death can occur independent of the previous neurosurgical procedure and that organ donation should always be considered in end-of-life decisions for patients with a fatal prognosis.

Evaluating the Effects of Time From Brain Death and Type of Inotrope Usage on Result of Heart Transplant: Results of 1-Year Follow-Up.

OBJECTIVES: Heart transplant is the most effective treatment in patients with advanced heart failure who are refractory to medical treatment. The brain death interval and type of inotrope We assessed the effects of these parameters on heart transplant outcomes. MATERIALS AND METHODS: In this follow-up study, we followed heart transplant recipients for 1 year to study patient survival, ejection fraction, adverse events, and organ rejection. We evaluated follow-up results on time from brainstem death test to the cross-clamp placement, as well as the type of inotrope used. RESULTS: Our study enrolled 54 heart transplant candidates. The inotrope dose was 3.66 ± 0.99 µg/kg/min, and the most used inotrope, with 28 cases (51.9%), was related to dopamine. Six cases (11.1%) of death and 1 case of infection after transplant were observed in recipients. The average ejection fraction of transplanted hearts before transplant, instantly at time of transplant, and 1 month, 6 months, and 1 year after transplant was 54.9 ± 0.68, 52.9 ± 10.4, 51.9 ± 10.7, 50.1 ± 10.9, and 46.8 ± 17, respectively; this decreasing trend over time was significant (P =.001). Furthermore, ejection fraction changes following transplant did not differ significantly in transplanted hearts regarding brain death interval and type of inotrope used. CONCLUSIONS: Our study revealed that cardiac output of a transplanted heart may decrease over time and the time elapsed from brain death, and both dopamine and norepinephrine could have negligible effects on cardiac function.

Calcineurin Inhibitor in NEuRoloGically deceased donors to decrease kidney delayed graft function study: study protocol of the CINERGY Pilot randomised controlled trial.

INTRODUCTION: Most solid organ transplants originate from donors meeting criteria for death by neurological criteria (DNC). Within the organ donor, physiological responses to brain death increase the risk of ischaemia reperfusion injury and delayed graft function. Donor preconditioning with calcineurin inhibition may reduce this risk. METHODS AND ANALYSIS: We designed a multicentre placebo-controlled pilot randomised trial involving nine organ donation hospitals and all 28 transplant programmes in the Canadian provinces of Ontario and Québec. We planned to enrol 90 DNC donors and their approximately 324 organ recipients, totalling 414 participants. Donors receive an intravenous infusion of either tacrolimus 0.02 mg/kg over 4 hours prior to organ retrieval, or a matching placebo, while monitored in an intensive care unit for any haemodynamic changes during the infusion. Among all study organ recipients, we record measures of graft function for the first 7 days in hospital and we will record graft survival after 1 year. We examine the feasibility of this trial with respect to the proportion of all eligible donors enrolled and the proportion of all eligible transplant recipients consenting to receive a CINERGY organ transplant and to allow the use of their health data for study purposes. We will report these feasibility outcomes as proportions with 95% CIs. We also record any barriers encountered in the launch and in the implementation of this trial with detailed source documentation. ETHICS AND DISSEMINATION: We will disseminate trial results through publications and presentations at participating sites and conferences. This study has been approved by Health Canada (HC6-24-c241083) and by the Research Ethics Boards of all participating sites and in Québec (MP-31-2020-3348) and Clinical Trials Ontario (Project #3309). TRIAL REGISTRATION NUMBER: NCT05148715.

Clinical Factors Associated With Mode of Death Following Cardiac Arrest.

BACKGROUND: Death after resuscitation from cardiac arrest is common. Although associated factors have been identified, knowledge about their relationship with specific modes of death is limited. OBJECTIVE: To identify clinical factors associated with specific modes of death following cardiac arrest. METHODS: This study involved a retrospective medical record review of patients admitted to a single health care center from January 2015 to March 2020 after resuscitation from cardiac arrest who died during their index hospitalization. Mode of death was categorized as either brain death, withdrawal of life-sustaining therapies due to neurologic causes, death due to medical causes, or withdrawal of life-sustaining therapies due to patient preference. Clinical characteristics across modes of death were compared. RESULTS: The analysis included 731 patients. Death due to medical causes was the most common mode of death. Compared with the other groups of patients, those with brain death were younger, had fewer comorbidities, were more likely to have experienced unwitnessed and longer cardiac arrest, and had more severe acidosis and hyperglycemia on presentation. Patients who died owing to medical causes or withdrawal of life-sustaining therapies due to patient preference were older and had more comorbidities, fewer unfavorable cardiac arrest characteristics, and fewer days between cardiac arrest and death. CONCLUSIONS: Significant associations were found between several clinical characteristics and specific mode of death following cardiac arrest. Decision-making regarding withdrawal of care after resuscitation from cardiac arrest should be based on a multimodal approach that takes account of a variety of personal and clinical factors.

An Ethics Committee's Evaluation of Normothermic Regional Perfusion (NRP) in 2018-Unsatisfactory Answers Then-and Now.

An adult university hospital ethics committee evaluated a proposed TA-NRP protocol in the fall of 2018. The protocol raised ethical concerns about violation of the Uniform Determination of Death Act and the prohibition known as the Dead Donor Rule, with potential resultant legal consequences. An additional concern was the potential for increased mistrust by the community of organ donation and transplantation. The ethics committee evaluated the responses to these concerns as unable to surmount the ethical and legal boundaries and the ethics committee declined to endorse the procedure. These concerns endure.

Criteria for brain death in Denmark.

In 1990, the Danish brain death legislation was adopted by the Danish Parliament. Each year, around 100 patients in Denmark fulfil criteria for brain death/death by neurological criteria (BD/DNC). In this review of current Danish criteria including the indication for ancillary investigation, which in Denmark is digital subtraction angiography (DSA), we conclude that the time has come to revise the national BD/DNC criteria. We propose that visible anoxic-ischaemic encephalopathy on brain CT after cardiac arrest does not require evaluation by ancillary testing, and that CT-angiography can be used instead of DSA.

The Unified Brain-Based Determination of Death Conceptually Justifies Death Determination in DCDD and NRP Protocols.

Organ donation after the circulatory determination of death requires the permanent cessation of circulation while organ donation after the brain determination of death requires the irreversible cessation of brain functions. The unified brain-based determination of death connects the brain and circulatory death criteria for circulatory death determination in organ donation as follows: permanent cessation of systemic circulation causes permanent cessation of brain circulation which causes permanent cessation of brain perfusion which causes permanent cessation of brain function. The relevant circulation that must cease in circulatory death determination is that to the brain. Eliminating brain circulation from the donor ECMO organ perfusion circuit in thoracoabdominal NRP protocols satisfies the unified brain-based determination of death but only if the complete cessation of brain circulation can be proved. Despite its medical and physiologic rationale, the unified brain-based determination of death remains inconsistent with the Uniform Determination of Death Act.

Systemic Inflammation Differences in Brain-vs. Circulatory-Dead Donors: Impact on Lung Transplant Recipients.

Brain death triggers a systemic inflammatory response. Whether systemic inflammation is different in lung donors after brain- (DBD) or circulatory-death (DCD) is unknown, but this may potentially increase the incidence of primary graft dysfunction (PGD) after lung transplantation. We compared the plasma levels of interleukin (IL)-6, IL-8, IL-10 and TNF-α in BDB and DCD and their respective recipients, as well as their relationship with PGD and mortality after LT. A prospective, observational, multicenter, comparative, cohort-nested study that included 40 DBD and 40 DCD lung donors matched and their respective recipients. Relevant clinical information and blood samples were collected before/during lung retrieval in donors and before/during/after (24, 48 and 72 h) LT in recipients. Incidence of PGD and short-term mortality after LT was recorded. Plasma levels of all determined cytokines were numerically higher in DBD than in DCD donors and reached statistical significance for IL-6, IL-10 and IL-8. In recipients with PGD the donor's plasma levels of TNF-α were higher. The post-operative mortality rate was very low and similar in both groups. DBD is associated with higher systemic inflammation than DCD donors, and higher TNF-α plasma levels in donors are associated with a higher incidence of PGD.

Effect of the Organ Donation Quality System on Donation Activity of Warsaw Hospitals.

BACKGROUND Like many other countries, Poland faces a shortage of transplantable organs despite implementing strategies to develop donation programs. Increasing the effectiveness of deceased organ donation programs requires the implementation of protocols and quality standards for the entire process. The aim of this study was to assess the organ donation potential in Warsaw hospitals (with and without implemented donation procedures) in the years 2017-2018, before the COVID-19 pandemic affected donation activity. The obtained results were compared with quality indicators established in the ODEQUS project and the European Commission project "Improving Knowledge and Practices in Organ Donation" (DOPKI). MATERIAL AND METHODS Retrospective analysis was performed of hospitalization and death causes (including deaths in the brain death mechanism) in the hospitals and intensive care units in 2017-2018. We divided 15 Warsaw hospitals into 2 groups: those with implemented quality programs for organ donation (n=4) and those without such programs (n=11). RESULTS Hospitals with procedures obtained significantly higher values than hospitals without procedures, but were lower than the values in DOPKI and ODEQUS. The success rate of the organ donation process after brain death recognition was comparable in all groups. The conversion rate to actual donors was 73% in hospitals with procedures compared to 68% in hospitals without procedures, significantly higher than in the 42% reported in the DOPKI project. CONCLUSIONS Low numbers of brain death declarations in Warsaw hospitals result from low recognition of deaths in the brain death mechanism. Implementing procedures at each hospital level will enable identification of critical points and comparison of solution outcomes.

Considerations for the use of porcine organ donation models in preclinical organ donor intervention research.

Use of animal models in preclinical transplant research is essential to the optimization of human allografts for clinical transplantation. Animal models of organ donation and preservation help to advance and improve technical elements of solid organ recovery and facilitate research of ischemia-reperfusion injury, organ preservation strategies, and future donor-based interventions. Important considerations include cost, public opinion regarding the conduct of animal research, translational value, and relevance of the animal model for clinical practice. We present an overview of two porcine models of organ donation: donation following brain death (DBD) and donation following circulatory death (DCD). The cardiovascular anatomy and physiology of pigs closely resembles those of humans, making this species the most appropriate for pre-clinical research. Pigs are also considered a potential source of organs for human heart and kidney xenotransplantation. It is imperative to minimize animal loss during procedures that are surgically complex. We present our experience with these models and describe in detail the use cases, procedural approach, challenges, alternatives, and limitations of each model.

Better liver transplant outcomes by donor interventions?

PURPOSE OF REVIEW: Donor risk factors and events surrounding donation impact the quantity and quality of grafts generated to meet liver transplant waitlist demands. Donor interventions represent an opportunity to mitigate injury and risk factors within donors themselves. The purpose of this review is to describe issues to address among donation after brain death, donation after circulatory determination of death, and living donors directly, for the sake of optimizing relevant outcomes among donors and recipients. RECENT FINDINGS: Studies on donor management practices and high-level evidence supporting specific interventions are scarce. Nonetheless, for donation after brain death (DBD), critical care principles are employed to correct cardiocirculatory compromise, impaired tissue oxygenation and perfusion, and neurohormonal deficits. As well, certain treatments as well as marginally prolonging duration of brain death among otherwise stable donors may help improve posttransplant outcomes. In donation after circulatory determination of death (DCD), interventions are performed to limit warm ischemia and reverse its adverse effects. Finally, dietary and exercise programs have improved donation outcomes for both standard as well as overweight living donor (LD) candidates, while minimally invasive surgical techniques may offer improved outcomes among LD themselves. SUMMARY: Donor interventions represent means to improve liver transplant yield and outcomes of liver donors and grafts.