Challenges and Possible Solutions to Donation After Circulatory Death in Turkey and the Middle East: Panel Discussion Summary Report.

The 20th century has witnessed the development of tissue and organ transplantation as the best therapeutic option for end-stage organ failure; however, organ shortages remain a prominent worldwide issue. Donation after circulatory death is an accepted practice in several countries around the world but also poses many challenges. Presently, controlled donations after circulatory death are not really in practice in Turkey and the Middle East, and the implementation of this practice seems complicated. To gather information about the possible reasons underlying the lack of organs from donors after circulatory death, as well as solutions, a discussion session took place during the International Symposium on "Brain Death and Circulatory Death" on November 29-30, 2023, in Ankara, Turkey. A description on different topics that were discussed is presented.

The Effects of 15 Golden Key Points to Increase the Family Consent Rate in Iran.

OBJECTIVES: In nations where organ donation is governed by the opt-in policy, the most crucial stage in the organ procurement process is the family approach and gaining the approval of families of decedents with brain death. In times of grief and sorrow, the ability of health care workers to communicate and have donation conversations is vital to the decision-making process of families and the subsequent consent rate. In this study, we investigated the effects of teaching important points to coordinators in the family approach and gaining consent of families for organ donation. MATERIALS AND METHODS: A new training program for Iranian coordinators was designed to increase the skills and knowledge of interviewers and increase the self-confidence of the coordinators. In the training program, 15 golden key points to have when meeting with families of brain dead decedents regarding organ donation consent were presented and discussed with participants. Three coordinating groups participated in this training program. The satisfaction rate of the families was assessed at comparable intervals (12 months for group 1, 6 months for group 2, and 3 months for group 3) before and after the training session to assess the continuity of the training impact. We used the Wilcoxon signed rank test for comparisons. RESULTS: The family consent rate was significantly different for all participants, before and after the 15 golden key points were presented, increasing from 50% to 62.5% (P = .037). In addition, participant sex (P = .051), previous training (P = .090), education (P = .068), and cooperation time (P = .008) had significant effects on family consent rate. CONCLUSIONS: Our training approach can increase the performance of coordinators in achieving family satisfaction.

The Role of Radionuclide Imaging in Brain Death Diagnosis.

Brain death is defined as the complete and irreversible cessation of the entire brain function, including the brainstem. For the most part, the diagnosis is clinical, and ancillary testing is only needed when clinical criteria are not satisfied. Differences exist in brain death diagnosis policy in the confirmation of brain death with ancillary testing and the particular test used. Demonstration of the absence of cerebral circulation is a reliable indicator of brain death. Currently, there are no agreed-on universal criteria for ancillary imaging investigation. However, several guidelines and meta-analyses have referred to radionuclide imaging as the most reliable, accurate, and validated ancillary imaging procedure in the confirmation of brain death. Whenever available, lipophilic agents should be preferred using tomographic imaging in all or as needed. False results may occur because of slight temporal delays in flow-function interaction, and such findings may carry prognostic information. Detectable cerebral circulation in the clinical presence of brain death most probably indicates that the process of dying is not yet complete. The results of radionuclide studies may also suggest that the loss of viability in a significant proportion of brain tissue is not compatible with life.

Donation after Brain Death and Circulatory Death in Turkey: Current Status.

Tissue and organ transplantation is the best treatment option for end-stage organ failure. However, organ shortage still remains to be the greatest challenge facing the field of organ transplantation. Millions of people die and are buried with healthy organs, which could save the lives of many patients who continue to wait on transplant lists. Countries must aim to work towards a system of matching organs as much as possible with the deceased donation to meet the growing demand for organs. This action will not only result in the reduction of organ trafficking activities but shall also make an enormous difference to those patients awaiting transplants where living organ donors are not an option. Donation after circulator death (DCD) has gained much attention over the last decade as one of the accepted practices in order to expand the donor pool. DCD donation takes place after declaration of death using cardio-respiratory criteria in contrast to donation after brain death (DBD) where neurological criteria are used. Although DCD remains a focus of interest and contributes to donor numbers in many countries, it also poses many challenges medically, ethically and legally.

Road To Deceased Donor Transplantation in Egypt.

In Egypt, there is presently a growing need to have a deceased donor transplant program. Egypt conducted its first kidney transplant from a living donor in 1976 and a first partial liver transplant in 2001. Since 2009, the Egyptian Health Authorities Combat Transplant Tourism in concordance with ethics codes and the Declaration of Istanbul Custodian Group has been in place. The Egyptian Transplantation Law of 2011 mentions that organs could be procured from deceased donors based on a will and on family consent. This law has had many critics, including religious authorities who have stressed that organs cannot be taken from a person with brain death because, in their view, life ends with death of all organs. Many intensivists disagree over the definition of death. In addition, the media has communicated contradicting and sometimes misleading health care information. Mummification is rooted in pharos practice and linked to religious beliefs. The ancient Egyptians believed that, by burying the deceased with their organs, they may rejoin with them in the afterlife. Since 2019, the transplant community in Egypt has started collaborations with international transplant organizations and campaigns with doctors and celebrities to donate their organs after death, which have stressed that a deceased donor program could help against end-stage organ mortality. In November 2022, after communications with politicians, President Abdelfattah El Sisi directed the government to establish a regional center for organ transplantation, which aimed to be the biggest in the Middle East and North Africa region. The new center will be part of a new medical city that would replace Nasser Medical Institution in Cairo, Egypt. The Ministry of Health issued an official form to be signed by a person before his death, accepting use of organs, to give hope and support to other patients in need.

Evolution of the Concept of Death.

The definition of death remains unresolved. To define death, one has to define the characteristics of a living person and to confirm whether an individual with brain death fulfils any of these characteristics. Although the concept of irreversible cessation of brain function is clear, controversy remains on the treatment of individuals with brain death and beating hearts. An individual with brain death but a beating heart is not breathing on his own and is dependent on medications and machines to maintain respiration, heartbeat, and blood pressure. Muslim scholars remain divided over the issue of whether death also means irreversible cessation of brain function. Questions remain on when it is permissible to remove vital organs for organ transplant. Groups have advocated for uniformity in law and medical practice on the definition of brain death.

Organ donation after extracorporeal cardiopulmonary resuscitation: a nationwide retrospective cohort study.

BACKGROUND: Limited data are available on organ donation practices and recipient outcomes, particularly when comparing donors who experienced cardiac arrest and received extracorporeal cardiopulmonary resuscitation (ECPR) followed by veno-arterial extracorporeal membrane oxygenation (ECMO) decannulation, versus those who experienced cardiac arrest without receiving ECPR. This study aims to explore organ donation practices and outcomes post-ECPR to enhance our understanding of the donation potential after cardiac arrest. METHODS: We conducted a nationwide retrospective cohort study using data from the Japan Organ Transplant Network database, covering all deceased organ donors between July 17, 2010, and August 31, 2022. We included donors who experienced at least one episode of cardiac arrest. During the study period, patients undergoing ECMO treatment were not eligible for a legal diagnosis of brain death. We compared the timeframes associated with each donor's management and the long-term graft outcomes of recipients between ECPR and non-ECPR groups. RESULTS: Among 370 brain death donors with an episode of cardiac arrest, 26 (7.0%) received ECPR and 344 (93.0%) did not; the majority were due to out-of-hospital cardiac arrests. The median duration of veno-arterial ECMO support after ECPR was 3 days. Patients in the ECPR group had significantly longer intervals from admission to organ procurement compared to those not receiving ECPR (13 vs. 9 days, P = 0.005). Lung graft survival rates were significantly lower in the ECPR group (log-rank test P = 0.009), with no significant differences in other organ graft survival rates. Of 160 circulatory death donors with an episode of cardiac arrest, 27 (16.9%) received ECPR and 133 (83.1%) did not. Time intervals from admission to organ procurement following circulatory death and graft survival showed no significant differences between ECPR and non-ECPR groups. The number of organs donated was similar between the ECPR and non-ECPR groups, regardless of brain or circulatory death. CONCLUSIONS: This nationwide study reveals that lung graft survival was lower in recipients from ECPR-treated donors, highlighting the need for targeted research and protocol adjustments in post-ECPR organ donation.

Lung Transplantation in Controlled Donation after Circulatory-Determination-of-Death Using Normothermic Abdominal Perfusion.

The main limitation to increased rates of lung transplantation (LT) continues to be the availability of suitable donors. At present, the largest source of lung allografts is still donation after the neurologic determination of death (brain-death donors, DBD). However, only 20% of these donors provide acceptable lung allografts for transplantation. One of the proposed strategies to increase the lung donor pool is the use of donors after circulatory-determination-of-death (DCD), which has the potential to significantly alleviate the shortage of transplantable lungs. According to the Maastricht classification, there are five types of DCD donors. The first two categories are uncontrolled DCD donors (uDCD); the other three are controlled DCD donors (cDCD). Clinical experience with uncontrolled DCD donors is scarce and remains limited to small case series. Controlled DCD donation, meanwhile, is the most accepted type of DCD donation for lungs. Although the DCD donor pool has significantly increased, it is still underutilized worldwide. To achieve a high retrieval rate, experience with DCD donation, adequate management of the potential DCD donor at the intensive care unit (ICU), and expertise in combined organ procurement are critical. This review presents a concise update of lung donation after circulatory-determination-of-death and includes a step-by-step protocol of lung procurement using abdominal normothermic regional perfusion.

Patient's last wish: organ donation after euthanasia. What conditions should be met to fulfill it?

Abstract: Organ donation after euthanasia (ODE) is a complex procedure involving the patient, the family, and the medical staff. Most organ donations occur from patients declared brain dead, and healthcare professionals rely on surrogate decisions, or the possible expression of ante-mortem will. Organ donation from deceased individuals is thus feasible under rigorous conditions, while direct donation after euthana-sia is not possible. The scientific community has not reached a shared conclusion. It is also difficult to quantify the number of patients who would be medically eligible to donate organs after euthanasia. In keep-ing with the core the principle of self-determination, any decision to undergo euthanasia (with or without organ donation) must be voluntary and not influenced by external pressures. For this reason, the physician should avoid informing the patient about the possibility of donating their organs before their request for euthanasia is evaluated. Just as noteworthy is the issue of healthcare providers' conscientious objec-tion and the receiving patient's right to know whether the transplanted organs come from a subject who underwent euthanasia. Finally, the patient who requests to end their life does so primarily because they are tormented by unbearable suffering and often expresses, as a last wish, the desire to exercise their free will regarding their own body. Organ donation after euthanasia would therefore seem to reinforce patient autonomy and self-esteem, thus giving a different meaning to their inevitable death, which is useful in saving the lives of others.

Orbital doppler ultrasound as an ancillary test for diagnosing brain death: A prospective, single blind comparative study.

OBJECTIVE: Transcranial Doppler ultrasound (TDUS), computed tomography angiography (CTA), and transcranial Doppler ultrasound to detect cerebral blood flow are among the adjunctive tests in diagnosing brain death. This study aimed to investigate the effectiveness of orbital doppler ultrasound (ODUS). METHODS: This prospective, single-blind study included 66 patients for whom brain death was to be diagnosed. Primary outcome measures were ODUS measurements, Ophthalmic artery peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive indices (RI) measurements recorded during the brain death determination process. Secondary outcome measures were computed tomography angio (CTA), transcranial Doppler ultrasound (TDUS), and demographic data. RESULTS: This study investigating the effectiveness of ODUS in diagnosing brain death provided diagnostic success with 100% sensitivity and 93% specificity compared to CT angiography. It was noted that anatomical variations may limit its use. CONCLUSION: ODUS was found to have high sensitivity and specificity in the diagnosis of clinical brain death. It may assist in early prognostic assessment and shorten patient follow-up and diagnostic processes.

Low frequency oscillations reflect neurovascular coupling and disappear after cerebral death.

Spectrum power analysis in the low frequency oscillations (LFO) region of functional near infrared spectroscopy (fNIRS) is a promising method to deliver information about brain activation and therefore might be used for prognostication in patients with disorders of consciousness in the neurocritical care unit alongside with established methods. In this study, we measure the cortical hemodynamic response measured by fNIRS in the LFO region following auditory and somatosensory stimulation in healthy subjects. The significant hemodynamic reaction in the contralateral hemisphere correlation with the physiologic electric response suggests neurovascular coupling. In addition, we investigate power spectrum changes in steady state measurements of cerebral death patients and healthy subjects in the LFO region, the frequency of the heartbeat and respiration. The spectral power within the LFO region was lower in the patients with cerebral death compared to the healthy subjects, whereas there were no differences in spectral power for physiological activities such as heartbeat and respiration rate. This finding indicates the cerebral origin of our low frequency measurements. Therefore, LFO measurements are a potential method to detect brain activation in patients with disorders of consciousness and cerebral death. However, further studies in patients are needed to investigate its potential clinical use.

[Brain death: from the transformation of medical concept to the change of medical practice].

The implementation of death determination by clinicians usually involves three steps: learning the concept of death, mastering the skills of death determination, and recording the results of death determination. Each process needs to be changed with the progress of medical science. The transformation of brain death concept is the establishment and formation of the latest cognition of "irreversible brain function", which needs to be completed based on the theoretical learning of recognized standards. The transformation of brain death determination is the learning and mastering of the latest skills of brain death determination, which requires relearning and retraining based on special technologies. The transformation of brain death determination is the habit formation of standardized records of brain death judgement results, which needs to be completed based on the continuous improvement of case quality control. The gradual advancement of the three steps will accelerate the process of determining brain death in China.

Active Donor Management Goals in Serial Donors After Brain Death.

OBJECTIVES: Management of potential organ donors is crucial in the donation process, considering that hemodynamic instability is quite common. MATERIALS AND METHODS: In the this single-center retrospective observational study, we analyzed 87 utilized brain death donors consecutively admitted to our intensive care unit from January 1, 2019, to December 31, 2022. We assessed the achievement of donor management goals during the observation period, and we also evaluated whether the achieve-ment of donor goals differed between younger and older donors (arbitrary age cutoff of 65 years). RESULTS: In our series, mean age of donors was 67 ± 18 y, and organ-per-donor ratio was 2.3. The number of donor goals significantly increased during the 6-hour observation period (P < .001) and all donor goals were achieved in most donors (84/87) at the end of the observation period with no changes in the use and dose of vasoactive drugs. With respect to age, the number of donor goals was significantly higher in older donors at first evaluation, but goals significantly increased in both age subgroups of donors at the end of the 6-hour observation period. CONCLUSIONS: Our data strongly suggested that a strict hemodynamic monitoring schedule allows the achievement of donor goals both in older and in younger brain death donors. We confirmed our previous findings that hemodynamic management in brain death donors is influenced by age. A strict hemodynamic monitoring schedule of brain death donors is useful to consistently achieve donor goals.

Liver Transplantation from Brain-Dead Donors with Hepatitis B or C in South Korea: A 2014-2020 Korean Organ Transplantation Registry Data Analysis.

BACKGROUND According to the current guidelines for liver transplantation (LT) of brain-dead donors with hepatitis B or C virus (HBV or HCV) in Korea, grafts from hepatitis B surface antigen (HBsAg)(+) or HCV antibody (anti-HCV)(+) donors must be transplanted only to HBsAg(+) or anti-HCV(+) recipients, respectively. We aimed to determine the current status and outcomes of brain-dead donor LT with HBV or HCV in Korea. MATERIAL AND METHODS This retrospective observational study included all LTs from brain-dead donors in the Korean Organ Transplantation Registry between April 2014 and December 2020. According to donor hepatitis status, 24 HBV(+), 1 HCV(+), and 1010 HBV(-)/HCV(-) donors were included. RESULTS Baseline/final model for end-stage liver disease score (MELD) for HBV(+), HCV(+), and HBV(-)/HCV(-) were 22.4±9.3/27.8±7.8, 16/11, and 33.0±15.4/35.5±7.1, respectively. MELD score of HBV (+) were lower than those of HBV(-)/HCV(-) (P<0.01). Five-year graft and patient survival rates of HBV(+) and HBV(-)/HCV(-) recipients were 81.7%/85.6%, and 76.6%/76.7%, respectively (P=0.73 and P=0.038). One-year graft and patient survival rates of HCV (+) graft recipients were both 100%. CONCLUSIONS No differences in graft and patient survival rates between HBV(+) and HBV(-)/HCV(-) groups were observed. Although accumulating the results of transplants from HBV (+) or HCV(+) grafts to HBV(-) or HCV(-) recipients is not possible owing to domestic regulations, Korea should conditionally permit transplantations from HBV(+) or HCV(+) grafts to HBV(-) or HCV(-) recipients by considering the risks and benefits based on foreign studies. Thereafter, we can accumulate the data from Korea and analyze the outcomes.

17ß-estradiol and methylprednisolone association as a therapeutic option to modulate lung inflammation in brain-dead female rats.

Introduction: Brain death (BD) is known to compromise graft quality by causing hemodynamic, metabolic, and hormonal changes. The abrupt reduction of female sex hormones after BD was associated with increased lung inflammation. The use of both corticoids and estradiol independently has presented positive results in modulating BD-induced inflammatory response. However, studies have shown that for females the presence of both estrogen and corticoids is necessary to ensure adequate immune response. In that sense, this study aims to investigate how the association of methylprednisolone (MP) and estradiol (E2) could modulate the lung inflammation triggered by BD in female rats. Methods: Female Wistar rats (8 weeks) were divided into four groups: sham (animals submitted to the surgical process, without induction of BD), BD (animals submitted to BD), MP/E2 (animals submitted to BD that received MP and E2 treatment 3h after BD induction) and MP (animals submitted to BD that received MP treatment 3h after BD induction). Results: Hemodynamics, systemic and local quantification of IL-6, IL-1ß, VEGF, and TNF-α, leukocyte infiltration to the lung parenchyma and airways, and adhesion molecule expression were analyzed. After treatment, MP/E2 association was able to reinstate mean arterial pressure to levels close to Sham animals (p<0.05). BD increased leukocyte infiltration to the airways and MP/E2 was able to reduce the number of cells (p=0.0139). Also, the associated treatment modulated the vasculature by reducing the expression of VEGF (p=0.0616) and maintaining eNOS levels (p=0.004) in lung tissue. Discussion: Data presented in this study show that the association between corticoids and estradiol could represent a better treatment strategy for lung inflammation in the female BD donor by presenting a positive effect in the hemodynamic management of the donor, as well as by reducing infiltrated leukocyte to the airways and release of inflammatory markers in the short and long term.

Anti-inflammatory effect of thalidomide in an experimental lung donor model of brain death.

Lung transplantation stands as a vital treatment for severe lung diseases, primarily sourcing organs from donors with brain death (BD). This research delved into the potential anti-inflammatory effects of thalidomide in rats with BD-induced lung complications. In this study twenty-four Wistar rats were divided into three groups: the control (CTR), brain death (BD) and brain death + thalidomide (TLD) groups. Post specific procedures, a 360 min monitoring period ensued. Comprehensive analyses of blood and heart-lung samples were conducted. Elevated IL-6 levels characterized both BD and TLD groups relative to the CTR (p = 0.0067 and p = 0.0137). Furthermore, TNF-α levels were notably higher in the BD group than both CTR and TLD (p = 0.0152 and p = 0.0495). Additionally, IL-1ß concentrations were significantly pronounced in both BD and TLD compared to CTR, with the BD group surpassing TLD (p = 0.0256). Immunohistochemical assessments revealed augmented NF-ĸB expression in the BD group in comparison to both CTR and TLD (p = 0.0006 and p = 0.0005). With this study we can conclude that BD induced acute pulmonary inflammation, whereas thalidomide manifested a notable capability in diminishing key inflammatory markers, indicating its prospective therapeutic significance in lung transplantation scenarios.

Pulmonary strain and end-expiratory lung volume during apnea test: a comparative analysis using electrical impedance tomography.

The apnea test, employed for brain death assessment, aims to demonstrate the absence of respiratory drive due to hypercapnia. The tracheal oxygen insufflation apnea test mode (I-AT) involves disconnecting the patient from invasive mechanical ventilation (iMV) for approximately 8 minutes while maintaining oxygenation. This test supports the diagnosis of brain death based on a specified increase in PaCO2. Common complications include hypoxemia and hemodynamic instability, and lung collapse-induced reduction in end-expiratory lung volume (EELV). In our case series utilizing electrical impedance tomography (EIT), we observed that continuous positive airway pressure during the apnea test (CPAP-AT) effectively mitigated lung collapse. This resulted in improved pulmonary strain compared to the disconnection of iMV. These findings suggest the potential benefits of routine CPAP-AT, particularly for potential lung donors, emphasizing the relevance of our study in providing quantitative insights into EELV loss and its association with pulmonary strain and potential lung injury.

La prueba de apnea es una técnica diagnóstica ampliamente utilizada para la evaluación de la muerte cerebral, con el objetivo de demostrar la ausencia de impulso respiratorio debido a la hipercapnia. La variante de la prueba de apnea con insuflación de oxígeno traqueal (I-AT) implica desconectar al paciente de la ventilación mecánica invasiva (iVM) durante aproximadamente 8 minutos, manteniendo la oxigenación mediante un catéter de insuflación. Esta prueba respalda el diagnóstico de muerte cerebral cuando se determina un aumento de la PaCO 2 superior a 20 mmHg en comparación con el valor inicial o un nivel de PaCO 2 superior a 60 mmHg al final de la prueba. En nuestra serie de casos, la implementación de la tomografía de impedancia eléctrica (EIT) reveló que la prueba de apnea con presión positiva continua (CPAPAT) mitiga eficazmente el colapso pulmonar. Este enfoque resulta en una mejora en la tensión pulmonar en comparación con la desconexión de iMV, demostrando su relevancia en el contexto de potenciales donantes de pulmones.

Consciousness and the Dying Brain.

The near-death experience has been reported since antiquity and is often characterized by the perception of light, interactions with other entities, and life recall. Near-death experiences can occur in a variety of situations, but they have been studied systematically after in-hospital cardiac arrest, with an incidence of 10 to 20%. Long attributed to metaphysical or supernatural causes, there have been recent advances in understanding the neurophysiologic basis of this unique category of conscious experience. This article reviews the epidemiology and neurobiology of near-death experiences, with a focus on clinical and laboratory evidence for a surge of neurophysiologic gamma oscillations and cortical connectivity after cardiac and respiratory arrest.