Brain Death Research Articles

Hypothermic oxygenated perfusion of the donor heart in heart transplantation: the short-term outcome from a randomised, controlled, open-label, multicentre clinical trial

Static cold storage (SCS) remains the gold standard for preserving donor hearts before transplantation but is associated with ischaemia, anaerobic metabolism, and organ injuries, leading to patient morbidity and mortality. We aimed to evaluate whether continuous, hypothermic oxygenated machine perfusion (HOPE) of the donor heart is safe and superior compared with SCS. We performed a multinational, multicentre, randomised, controlled, open-label clinical trial with a superiority design at 15 transplant centres across eight European countries. Adult candidates for heart transplantation were eligible and randomly assigned in a 1:1 ratio. Donor inclusion criteria were age 18-70 years with no previous sternotomy and donation after brain death. In the treatment group, the preservation protocol involved the use of a portable machine perfusion system ensuring HOPE of the resting donor heart. The donor hearts in the control group underwent ischaemic SCS according to standard practices. The primary outcome was time to first event of a composite of either cardiac-related death, moderate or severe primary graft dysfunction (PGD) of the left ventricle, PGD of the right ventricle, acute cellular rejection at least grade 2R, or graft failure (with use of mechanical circulatory support or re-transplantation) within 30 days after transplantation. We included all patients who were randomly assigned, fulfilled inclusion and exclusion criteria, and received a transplant in the primary analysis and all patients who were randomly assigned and received a transplant in the safety analyses. This trial was registered with ClicalTrials.gov (NCT03991923) and is ongoing. A total of 229 patients were enrolled between Nov 25, 2020, and May 19, 2023. The primary analysis population included 204 patients who received a transplant. There were no patients who received a transplant lost to follow-up. All 100 donor hearts preserved with HOPE were transplantable after perfusion. The primary endpoint was registered in 19 (19%) of 101 patients in the HOPE group and 31 (30%) of 103 patients in the SCS group, corresponding to a risk reduction of 44% (hazard ratio 0·56; 95% CI 0·32-0·99; log-rank test p=0·059). PGD was the primary outcome event in 11 (11%) patients in the HOPE group and 29 (28%) in the SCS group (risk ratio 0·39; 95% CI 0·20-0·73). In the HOPE group, 63 (65%) patients had a reported serious adverse event (158 events) versus 87 (70%; 222 events) in the SCS group. Major adverse cardiac transplant events were reported in 18 (18%) and 33 (32%) patients in the HOPE and SCS group (risk ratio 0·56; 95% CI 0·34-0·92). Although there was not a significant difference in the primary endpoint, the 44% risk reduction associated with HOPE was suggested to be a clinically meaningful benefit. Post-transplant complications, measured as major adverse cardiac transplant events, were reduced. Analysis of secondary outcomes suggested that HOPE was beneficial in reducing primary graft dysfunction. HOPE in donor heart preservation addresses the existing challenges associated with graft preservation and the increasing complexity of donors and heart transplantation recipients. Future investigation will help to further elucidate the benefit of HOPE. XVIVO Perfusion.

Coronary computed tomographic angiographic imaging of cardiac allograft preserved in Paragonix SherpaPak Cardiac Transport System

Donation after circulatory death (DCD) heart transplantation is emerging as an alternative pathway to traditional donation after brain death (DBD) to expand the heart donor pool. Greater adoption of DCD heart allografts is hampered by the logistical and ethical constraints to perform invasive ante mortem testing, thus limiting the capacity for the standard donor organ quality evaluation. Identification of the absence of coronary artery disease in patients at risk is an essential prerequisite for organ acceptance by an implant institution. This case presents the novel approach to the examination of coronary arteries in a cardiac allograft. We demonstrated that the coronary computed tomographic angiographic (CTA) imaging of an ex-situ non-beating cardiac allograft preserved after recovery in SherpaPak® Cardiac Transport System (CTS) is technically feasible. The images are of good quality and allow for 3D reconstruction as well as quantification of coronary lesions.

Impact of Warm Ischemia Time on Donation After Circulatory Death Kidney Transplant Outcomes.

Efforts to address the shortage of donor organs include increasing the use of renal allografts from donors after circulatory death (DCD). While warm ischemia time (WIT) is thought to be an important factor in DCD kidney evaluation, few studies have compared the relationship between WIT and DCD kidney outcomes, and WIT acceptance practices remain variable. We conducted a single-center retrospective review of all adult patients who underwent deceased donor kidney transplantation from 2000 to 2021. We evaluated the impact of varied functional warm ischemia time (fWIT) in controlled DCD donors by comparing donor and recipient characteristics and posttransplant outcomes between high fWIT (>60min), low fWIT (≤60min), and kidneys transplanted from donors after brain death (DBD). Two thousand eight hundred eleven patients were identified, 638 received low fWIT DCD, 93 received high fWIT DCD, and 2080 received DBD kidneys. There was no significant difference in 5-year graft survival between the DCD low fWIT, high fWIT, and DBD groups, with 84%, 83%, and 83% of grafts functioning, respectively. Five-year patient survival was 91% in the low fWIT group, 92% in the high fWIT group, and 90% in the DBD group. An increase in kidney donor risk index (KDRI) (HR 3.37, 95% CI=2.1-5.7) and high CIT compared to low CIT (HR 2.12, 95% CI=1.4-3.1) have higher hazard ratios for 1-year graft failure. Increased acceptance of kidneys from selected DCD donors with prolonged fWIT may present an opportunity to increase kidney utilization while preserving outcomes. Our group specifically prioritizes the use of kidneys from younger donors, with lower KDPI, and without acute kidney injury, or risk factors for underlying chronic kidney disease.

Increasing Multiorgan Heart Transplantations From Donation After Circulatory Death Donors in the United States.

Donation after circulatory death (DCD) donors are becoming an important source of organs for heart-transplantation (HT), but there are limited data regarding their use in multiorgan-HT. Between January 2020 and June 2023, we identified 87 adult multiorgan-HTs performed using DCD-donors [77 heart-kidney, 6 heart-lung, 4 heart-liver] and 1494 multiorgan-HTs using donation after brain death (DBD) donors (1141 heart-kidney, 165 heart-lung, 188 heart-liver) in UNOS. For heart-kidney transplantations (the most common multiorgan-HT combination from DCD-donors), we also compared donor/recipient characteristics, and early outcomes, including 6-month mortality using Kaplan-Meier (KM) and Cox hazards-ratio (Cox-HR). Use of DCD-donors for multiorgan-HTs in the United States increased from 1% in January to June 2020 to 12% in January-June 2023 (p < 0.001); but there was a wide variation across UNOS regions and center volumes. Compared to recipients of DBD heart-kidney transplantations, recipients of DCD heart-kidney transplantations were less likely to be of UNOS Status 1/2 at transplant (35.06%vs. 69.59%) and had lower inotrope use (22.08%vs. 43.30%), lower IABP use (2.60%vs. 26.29%), but higher durable CF-LVAD use (19.48%vs. 12.97%), all p < 0.01. Compared to DBD-donors, DCD-donors used for heart-kidney transplantations were younger [28(22-34) vs. 32(25-39) years, p=0.004]. Recipients of heart-kidney transplantations from DCD-donors and DBD-donors had similar 6-month survival using both KM analysis, and unadjusted and adjusted Cox-HR models, including in propensity matched cohorts. Rates of PGF and in-hospital outcomes were also similar. Use of DCD-donors for multiorgan-HTs has increased rapidly in the United States and early outcomes of DCD heart-kidney transplantations are promising.

Extended Criteria Donor Use in Lung Transplants From Donation After Controlled Circulatory Death

BackgroundMost institutions apply the criteria for controlled donation after cardiac death (cDCD) lung retrieval identical to the criteria for donation after brain death (DBD). The availability of extended criteria donor (ECD) in lung transplants from cDCD remains unclear. MethodsThe United Network for Organ Sharing (UNOS) database was queried for adult lung transplants from cDCD, from May 03, 2005, to March 15, 2022. ECDs were defined by one or more items at variance from standard criteria: age 55 years or more, PaO2:FiO2 300 or less, smoking 20 pack-years or more, diabetes, or purulent secretions upon bronchoscopy. Recipients were divided into the standard criteria donor (SCD) group and the ECD group, and assessed for short- and long-term survival and postoperative events. ResultsAmong 827 records, the SCD and ECD group showed no differences in 5-year (P = .56) survival. No significant differences were found in 30-day, 90-day, 1-year mortality and postoperative outcomes before discharge, whether in length of hospital stay, rate of ventilator support for >48 hours or reintubation, incidence of grade 3 PGD 72 hours posttransplant, acute rejection, or dialysis. None of the 5 donor factors used as criteria for lung retrieval was independently associated with cDCD recipient survival. ConclusionsUsing donor lungs that extend the DBD criteria may be a safe strategy in cDCD lung transplantation. However, the current criteria may not be a perfect fit for cDCD lung retrieval. The specific DCD criteria for standard lung retrieval need to be determined.

Graft Steatosis and Donor Diabetes Mellitus Additively Impact on Recipient Outcomes After Liver Transplantation-A European Registry Study.

Biopsy-proven severe graft steatosis is associated with adverse outcomes after liver transplantation. The concomitant presence of metabolic risk factors might further increase this risk. We studied the association between graft steatosis and metabolic risk factors in the donor, with recipient outcomes after liver transplantation. We analyzed data from all consecutive first adult full-graft donation after brain death (DBD) liver transplantations performed in the Eurotransplant region between 2010 and 2020. The presence of graft steatosis and metabolic risk factors was assessed through a review of donor (imaging) reports, and associations with recipient retransplantation-free survival were studied through survival analyses. Of 12174 transplantations, graft steatosis was detected in 2689 (22.1%), and donor diabetes mellitus (DM), hypertension, and dyslipidemia were present in 1245 (10.2%), 5056 (41.5%), and 524 (4.3%). In multivariable Cox regression analysis, graft steatosis (adjusted HR [aHR] 1.197, p<0.001) and donor DM (aHR 1.157, p=0.004) were independently associated with impaired retransplantation-free survival. Graft steatosis and donor DM conferred an additive risk of retransplantation or death (DM alone, aHR: 1.156 [p=0.0185]; steatosis alone, aHR: 1.200 [p<0.001]; both steatosis and DM, aHR: 1.381 [p<0.001]). Findings were consistent in sensitivity analyses focusing on retransplantation-free survival within 7 days. Graft steatosis and donor diabetes mellitus additively increase the risk of retransplantation or death in adult DBD liver transplantation. Future studies should focus on methods to assess and improve the quality of these high-risk grafts. Until such time, caution should be exercised when considering these grafts for transplantation.

Survival, function, and immune profiling after beating heart transplantation

ObjectiveEx vivo normothermic perfusion of cardiac allografts has expanded the donor pool for heart transplant. Using a beating heart implantation method avoids the second cardioplegic arrest and subsequent ischemia-reperfusion injury typically associated with ex vivo heart perfusion. We sought to describe our institutional experience with beating heart transplantation. MethodsThis was a single-institution retrospective study of adult patients who underwent heart transplantation using ex vivo heart perfusion (EVHP) and a beating heart implantation technique between October 2022 and March 2024. Primary outcomes of interest included survival, initiation of mechanical circulatory support, and rejection. A subanalysis of our institutional series of nonbeating deceased after circulatory death (DCD) heart transplantations was performed as well. ResultsTwenty-four patients underwent isolated heart transplantation with the use of ex vivo heart perfusion and beating heart implantation between October 2022 and March 2024; 21 (87.5%) received hearts from DCD donors, and 3 (12.5%) received hearts from deceased after brain death (DBD) donors. The median duration of follow-up was 192 days (interquartile range [IQR], 124-253.5 days), and 23 out of 24 patients (95.8%) were alive at last follow-up. No patients required initiation of mechanical circulatory support. The majority of patients had pathologic grade 0 rejection at the time of biopsy (n = 16; 66.7%), and the median cell-free DNA percent was 0.04% (IQR, 0.04%-0.09%). The rate of mechanical circulatory support initiation in the 22-patient nonbeating DCD heart transplant cohort was significantly higher, at 36.4% (P < .005). ConclusionsA beating heart implantation technique can be used for transplantation of DCD and DBD hearts on EVHP and is associated with excellent survival and low levels of rejection.

Non-invasive Respiratory Support or Intubation during Stabilization after Birth and Neonatal and Neurodevelopmental Outcomes in Infants Born Preterm at 23-25 Weeks of Gestation

To examine the association between non-invasive respiratory support (NRS) or tracheal intubation (TI) during stabilization in infants born at 23-25 weeks of gestation and severe brain injury (sBI) or death, and significant neurodevelopmental impairment (sNDI). A retrospective cohort study of infants born at 230/7-256/7 weeks of gestation in Canada. We compared infants successfully managed with NRS or TI during 30 minutes after birth. The primary outcomes were sBI or death before discharge, and sNDI among survivors with follow-up data at 18-24 months corrected age. The associations between exposures and outcomes were assessed using logistic regression models, and propensity score matched (PSM) analyses. The mean (SD) of gestational age and birth weight were 24.6 (0.6), 24.3 (0.7) weeks [p <0.01], and 757 (173), 705 (130) grams [p <0.01] in the NRS, and TI groups, respectively, and 77% of infants in the NRS group were intubated by 7 days of age. sBI or death occurred in 25% (283/1118), and 36% (722/ 2012) of infants in the NRS and TI groups, respectively (adjusted odds ratio [aOR] and 95% confidence interval [CI] 0.74 [0.60, 0.91]). Among survivors with follow-up data, sNDI occurred in 17% (96/551), and 23% (218/937) of infants in the NRS and TI groups, respectively (aOR [95% CI] 0.77 [0.60, 0.99]). In the PSM analyses (NRS vs TI), results were consistent for sBI or death (OR [95% CI] 0.72 [0.60, 0.86]), but not for sNDI (OR [95% CI] 0.78 [0.58, 1.05]). Infants born at 23-25 weeks who were successfully managed with NRS, compared with TI, in the first 30 minutes after birth had lower odds of sBI or death before discharge, but had no significant differences in neurodevelopmental outcomes among survivors.

A brain death model with slow induction for experimental studies of organ donation

Aim. To test in experiment a pathogenetically adequate model of brain death due to increased intracranial pressure with gradual induction, allowing the evaluation of the changes occurring in the organs of a potential donor.Materials and methods. 6–8 months old outbred male rats of the experimental group (n = 18) and the control group (n = 8) were anesthetized, the left common carotid artery was catheterized to record systolic, diastolic blood pressure (BP) and heart rate (HR), the mean BP (MBP) was calculated. After transfer to artifi cial ventilation, brain death was simulated in the experimental group using the developed method.Results. All animals in the experimental group suffered brain death 30 minutes from the start of the experiment;10 rats (56%) died within 3 hours due to progression of circulatory failure. Initially, in anesthetized animals, MBP was 101 (90; 105) mm Hg, HR 310 (297; 315) beats/min. After 5 minutes from the start of brain death induction, MBP increased to 147 (140; 150) mm Hg (p = 0.01), HR to 396 (384; 406) beats/min (p = 0.03). Further, within 20 minutes there was a decrease in MBP to 94 (90; 100) mm Hg and HR to 290 beats/min. During the observation period from 26 to 90 minutes, there was a stabilization of MBP at the level of 87–92 mm Hg, there was a tendency to bradycardia with HR from 263 to 274 beats/min (p = 0.01). Then after 120–150 minutes from the beginning of brain death induction, MBP continued to decrease to 75–80 mmHg (p = 0,03), HR to 256–264 beats/min (p = 0,01). At the end of the experiment, despite volemic support, MBP decreased to 64 (61; 67) mm Hg (p = 0.02), bradycardia worsened with HR to 250 (248; 260) beats/min (p = 0.01), indicating the hemodynamic decompensation.Conclusion. The results of experimental testing of an animal brain death model on outbred rats showed that this model is pathogenetically adequate and useful to assess the condition of potential donor organs within 3 hours after the induction of brain death.

Spatial transcriptomics at the brain-electrode interface in rat motor cortex and the relationship to recording quality

Study of the foreign body reaction to implanted electrodes in the brain is an important area of research for the future development of neuroprostheses and experimental electrophysiology. After electrode implantation in the brain, microglial activation, reactive astrogliosis, and neuronal cell death create an environment immediately surrounding the electrode that is significantly altered from its homeostatic state. Objective. To uncover physiological changes potentially affecting device function and longevity, spatial transcriptomics (ST) was implemented to identify changes in gene expression driven by electrode implantation and compare this differential gene expression to traditional metrics of glial reactivity, neuronal loss, and electrophysiological recording quality. Approach. For these experiments, rats were chronically implanted with functional Michigan-style microelectrode arrays, from which electrophysiological recordings (multi-unit activity, local field potential) were taken over a six-week time course. Brain tissue cryosections surrounding each electrode were then mounted for ST processing. The tissue was immunolabeled for neurons and astrocytes, which provided both a spatial reference for ST and a quantitative measure of glial fibrillary acidic protein and neuronal nuclei immunolabeling surrounding each implant. Main results. Results from rat motor cortex within 300 µm of the implanted electrodes at 24 h, 1 week, and 6 weeks post-implantation showed up to 553 significantly differentially expressed (DE) genes between implanted and non-implanted tissue sections. Regression on the significant DE genes identified the 6–7 genes that had the strongest relationship to histological and electrophysiological metrics, revealing potential candidate biomarkers of recording quality and the tissue response to implanted electrodes. Significance. Our analysis has shed new light onto the potential mechanisms involved in the tissue response to implanted electrodes while generating hypotheses regarding potential biomarkers related to recorded signal quality. A new approach has been developed to understand the tissue response to electrodes implanted in the brain using genes identified through transcriptomics, and to screen those results for potential relationships with functional outcomes.

Healthcare Worker Attitudes to Living Donation Prior to Planned Withdrawal of Care.

This study assesses the attitudes of healthcare practitioners toward Living Donation Prior to Planned Withdrawal of Care (LD-PPW): the recovery of a living donor organ before withdrawal of life-sustaining measures in a patient who does not meet criteria for brain death, but for whom medical care toward meaningful recovery is deemed futile. An electronic survey was administered to 1735 members of the American Society of Transplant Surgeons mailing list with 187 responses (10.8%). Data from this study revealed that 70% of responding practitioners agreed with LD-PPW due to principles of beneficence and autonomy. Also, 65% of participants felt confident in their ability to declare the futility of care and 70% felt that LD-PPW should be added as an option when registering to become an organ donor. Currently, nearly half of all donation after circulatory determination of death do not proceed to donation. LD-PPW has been proposed as an alternative procedure targeted at increasing the quality and quantity of transplantable organs while respecting the donor's right to donate, though its implementation has been hindered by concerns over public and provider perception. This study revealed support for LD-PPW among healthcare practitioners as an alternative procedure to increase the quality and quantity of transplantable organs while respecting the donor's right to donate.

Impact of Donor Warm Ischemia Time on Graft Survival for Donation After Circulatory Death Kidney Transplantation.

The utilization of kidneys donated after circulatory death (DCD) is an important strategy to address the ongoing shortage of organs suitable for transplantation in the United States. However, the nonuse rate of DCD kidneys remains high compared with kidneys donated after brain death (DBD) because of concerns regarding the injury incurred during donor warm ischemia time (DWIT). Therefore, we investigated the impact of DWIT on the risk of death-censored graft failure after DCD kidney transplantation (KT). Retrospective analysis was conducted on DCD KTs using the Standard Transplant Analysis and Research data set. The association of DWIT with death-censored graft failure was evaluated using multivariable Cox proportional hazard regression, with reference to DCD KTs with Kidney Donor Risk Index (KDRI) of ≤0.78 and the median DWIT of 26 min. A total of 28 032 DCD kidney-alone transplants between January 2010 and December 2021 were studied. When stratified by KDRI, increasing DWIT was associated with a clinically significant increased risk for death-censored graft failure only in the subset of kidneys with KDRI >1.14 but not in those with KDRI >0.78-≤0.94 and >0.94-≤1.14, compared with the reference group. We suggest that clinicians should not decline kidneys on the basis of DWIT in favor of potential offers of DBD or other DCD kidneys with shorter DWIT, provided that their KDRI scores are within an acceptable limit. Our study highlights opportunities for more efficient usage of DCD kidneys and improving the shortage of transplantable organs.

Identifying Variation in Intraoperative Management of Brain-Dead Organ Donors and Opportunities for Improvement: A Multicenter Perioperative Outcomes Group Analysis.

Intraoperative events and clinical management of deceased organ donors after brain death are poorly characterized and may consequently vary between hospitals and organ procurement organization (OPO) regions. In a multicenter cohort, we sought to estimate the incidence of hypotension and anesthetic and nonanesthetic medication use during organ recovery procedures. We used data from electronic anesthetic records generated during organ recovery procedures from brain-dead adults across a Multicenter Perioperative Outcomes Group (MPOG) cohort of 14 US hospitals and 4 OPO regions (2014-2020). Hypotension, defined as mean arterial pressure or MAP <60 mm Hg for at least 10 cumulative minutes was the primary outcome of interest. The associations between hypotension and age, sex, race, anesthesia time, OPOs, and OPO case volume were examined using multivariable mixed-effects Poisson regression analyses with robust standard error estimates. We calculated intraclass correlation coefficients (ICCs) to describe the variation between-MPOG centers and the OPO regions in the use of medications, time of the operation, and duration of the operation. We examined 1338 brain-dead adult donors, with a mean age of 42± (standard deviation [SD] 15) years; 60% (n = 801) were males and 67% (n = 891) non-Hispanic White. During the entire intraoperative monitoring period, 321 donors (24%, 95% confidence interval [CI], 22%-26%) had hypotension for a median of 13.8% [quartile1-quartile 3: 9.4%-21%] of the monitoring period and a minimum of 10 minutes to a maximum of 96 minutes [(median: 17, quartile1-quartile 3: 12-24]). The probability having hypotension in donors 35 to 64 years and 65 years and older were approximately 30% less than in donors 18 to 34 years of age (adjusted relative risk ratios, aRR, 0.68, 95% CI, 0.55-0.82, aRR, 0.63, 95% CI, 0.42-0.94, respectively). Donors received intravenous heparin (96.4%, n = 1291), neuromuscular blockers (89.5%, n = 1198), vasoactive medications (82.7%, n = 1108), crystalloids (76.2%, n = 1020), halogenated anesthetic gases (63.5%, n = 850), diuretics (43.8%, n = 587), steroids (16.7%, n = 224), and opioids (23.2%, n = 310). The largest practice heterogeneity observed between the MPOG center and OPO regions was steroids (between-center ICCs = 0.65, 95% CI, 0.62-0.75, between-region ICCs = 0.39, 95% CI, 0.27-0.63) and diuretics (between-center ICCs = 0.44, 95% CI, 0.36-0.6, between-region ICCs = 0.30, 95% CI, 0.22-0.49). Despite guidelines recommending maintenance of MAP >60 mm Hg in adult brain-dead organ donors, hypotension during recovery procedures was common. Future research is needed to clarify the relationship between intraoperative events with donation and transplantation outcomes and to identify best practices for the anesthetic management of brain-dead donors in the operating room.

Predicting outcomes after transplantation of deceased donor kidneys of marginal quality within the Eurotransplant service area.

Kidneys of marginal quality are increasingly being used to overcome the shortage of donor organs. However, accurate prediction of outcome is needed to optimise the use of these kidneys. We aimed to test the performance of a recently proposed score consisting of delayed graft function (DGF), renal function recovery (RFR), and glomerular filtration rate (GFR) &lt;30 ml/min per 1.73 m2 90 days after transplantation for risk assessment of patient and graft survival. A total of 221 adult brain death donors with marginal kidneys, transplanted into 223 recipients within Eurotransplant were included in the analysis. Multivariable Cox proportional hazards models were constructed to assess death-censored and all-cause censored graft failure and recipient mortality at one and three years. Recipients with DGF had a higher risk of death-censored graft loss (HR, 95%CIs: 3.058 (1.195 - 7.825)). Recipients with a GFR &lt;30ml/min/1.73m² at 90 days after transplantation had a higher risk of death censored and all-cause graft failure (HR, 95%CIs: 2.122 (1.129-3.990 and 2.122 (1.129 - 3.990)). None of the three components of the proposed score was associated with a higher risk of mortality. DGF and eGFR &lt;30 ml/min/1.73m² but not RFR at 90 days predicted graft failure after transplantation of marginal kidneys. However, no combination of these factors was able to predict short-term patient and graft survival.

Brain Death and the Role of the Anaesthesiologist: A Review

Brain death is a critical and complex diagnosis in the medical field, necessitating precise and methodical evaluation. Anaesthesiologists play a pivotal role in this process, ensuring that the determination of brain death is accurate and ethically sound. This review examines the criteria and protocols for diagnosing brain death, the physiological and clinical challenges involved, and the crucial contributions of anaesthesiologists. We discuss the integration of neuroimaging and electrophysiological studies, the management of potential confounders such as intoxication or hypothermia, and the importance of maintaining homeostasis in potential organ donors. The involvement of anaesthesiologists in organ donation procedures, including maintaining optimal organ function and coordinating with transplant teams, is also explored. By highlighting the multi-faceted responsibilities of anaesthesiologists in the context of brain death, this review underscores their essential role in ensuring that diagnoses are made with the highest degree of accuracy and ethical consideration.

Why do children not survive extracorporeal membrane oxygenation?

Extracorporeal membrane oxygenation (ECMO) is used in critically ill children with cardiac and/or respiratory failure. Use is increasing in children with high-risk comorbidities. Reasons children do not survive ECMO are poorly described. Describe characteristics and cause of death, compare mortality in children with high-risk comorbidities, evaluate mortality trends over a decade. All children <18 years old who received ECMO at this institution from 1 January 2011 to 31 December 2020 were described and categorised by outcome: died on or <48 h post-ECMO, died ≥48 h post-ECMO, survived to hospital discharge. Children who did not survive ECMO (DNSE) were categorised to: ECMO withdrawal for irrecoverable original condition, withdrawal for poor prognosis neurological condition, brain death, withdrawal for poor prognosis with multiple complex conditions, and unsupportable. Poison regression was used to analyse survival trends. Four hundred twenty-eight children received ECMO, 19% DNSE, 14% died ≥48 h post-ECMO and 67% survived. ECMO was electively withdrawn for irrecoverable original condition (39%), poor prognosis for neurological condition (32%) or multiple complex conditions (18%). One hundred twenty-two children had ≥1 high-risk comorbidity. Children with genetic syndromes (58%), risk-adjusted congenital heart surgery score-1 ≥4 (53%), primary immunodeficiency (50%) had lower hospital survival. No children with malignancy/bone marrow transplant survived to hospital discharge. Overall hospital survival was 67%, with no significant change during the study period (P-trend = 0.99). Children who DNSE have therapy electively withdrawn for irrecoverable disease or poor prognosis. Children with high-risk comorbidities have a reasonable chance of survival. This study informs clinicians ECMO may be a therapeutic option.

Brain death: A review of the latest guidelines.

The incidence of brain death/death by neurologic criteria (BD/DNC) among all hospital deaths in the US is approximately 2.06% or 15,000-20,000 cases annually. This article reviews the latest guidelines for adult and pediatric BD/DNC. Although there have not been many changes to the guidelines over the years, BD/DNC guideline updates maintain consistency in determining BD/DNC.

Normothermic Machine Perfusion and Normothermic Regional Perfusion of DCD Kidneys Before Transplantation: A Systematic Review.

To overcome organ shortages, donation after circulatory death (DCD) kidneys are being increasingly used for transplantation. Prior research suggests that DCD kidneys have inferior outcomes compared with kidneys donated after brain death. Normothermic machine perfusion (NMP) and normothermic regional perfusion (NRP) may enhance the preservation of DCD kidneys and improve transplant outcomes. This study aimed to review the evidence surrounding NMP and NRP in DCD kidney transplantation. Two independent reviewers conducted searches for all publications reporting outcomes for NMP and NRP-controlled DCD kidneys, focusing on delayed graft function, primary nonfunction, graft function, graft survival, and graft utilization. Weighted means were calculated for all relevant outcomes and controls. Formal meta-analyses could not be conducted because of significant heterogeneity. Twenty studies were included for review (6 NMP studies and 14 NRP studies). Delayed graft function rates seemed to be lower for NRP kidneys (24.6%) compared with NMP kidneys (54.3%). Both modalities yielded similar outcomes with respect to primary nonfunction (NMP 3.3% and NRP 5.6%), graft function (12-mo creatinine 149.3 μmol/L for NMP and 129.9 μmol/L for NRP), and graft utilization (NMP 83.3% and NRP 89%). Although no direct comparisons exist, our evidence suggests that both modalities have good short- and medium-term graft outcomes and high graft survival rates. Current literature demonstrates that both NMP and NRP are feasible strategies that may increase donor organ utilization while maintaining acceptable transplant outcomes and likely improved outcomes compared with cold-stored DCD kidneys. Further research is needed to directly compare NRP and NMP outcomes.

Cadaveric organ donation: Indian perspective

Cadaveric organ donation in India, although started long back; its present status is not favourable. The percentage gain is very slow in comparison to most of the country even after having proper legislation. There are many reasons for this, lack of awareness being the most common. Most of the people does not know the concept of brain death. Although government and many NGOs are attached with it and are trying their level best to communicate with people for this noble cause, they have not yet reached the expected goal.To boost up the process of cadaveric organ donation, the hospitals and their staff including doctors must play a vital role. Hence, knowledge and orientation of such potential group is important for further processing because in most of the hospitals even doctors are not well-informed about the legal and ethical aspects of organ donation. If all the weak locus are addressed properly, we can definitely achieve the goals within a short span of time.

Donor Conditioning and Organ Pre-Treatment Prior to Kidney Transplantation: Reappraisal of the Available Clinical Evidence.

Therapeutic measures aimed at optimising organ function prior to transplantation-whether by conditioning the donor after determination of brain death or by improving organ preservation after kidney removal-have the potential to enhance outcomes after transplantation. The particular advantage is that, unlike any optimised immunosuppressive therapy, a favourable effect can be achieved without side effects for the organ recipient. In recent years, several such measures have been tested in controlled clinical trials on large patient cohorts following kidney transplantation. Hypothermic pulsatile machine perfusion, in particular, has become the focus of interest, but interventions in the donor prior to organ removal, such as the administration of low-dose dopamine until the start of cold perfusion as an example of conditioning antioxidant therapy and therapeutic donor hypothermia in the intensive care unit after brain death confirmation, have also significantly reduced the frequency of dialysis after transplantation with far less effort and cost. With regard to benefits for graft survival, the database for all procedures is less clear and controversial. The aim of this review article is to re-evaluate the available clinical evidence from large multicentre controlled trials, which have also significantly influenced later meta-analyses, and to assess the significance for use in routine clinical practice.