In October 1997, the “ Organ Transplantation Act” was established, and it became possible to donate organs under brain death in Japan. And 13 years later, in 2010, the law was revised to donate organs for children who were legally diagnosed with brain death. If the person’s intention regarding organ donation is unknown, it became possible to donate organs under brain death with the consent of the family. As a result, the number of donation of organs under brain death tended to increase every year, and the number was 97 cases in 2019. However, the existence of various burdens on organ donation facilities is also an issue, which is the background for hesitating to present so-called options. We suppose that it is necessary to solve such problems in order to realize the intention of patients and their families regarding organ donation. In this paper, in order to understand the issues of organ donation for the medical staff, we will look back on the history and transition of the organ donation system in Japan and describe its problems and solutions.

In 2020, the international consensus for determining brain death/death of neurological criteria (BD/DNC) was published in the Journal of the American Medical Association. This consensus provides a novel definition and concept of brain death, including existing whole brain death and brainstem death. It was created as the minimum standard for legislation action worldwide. This review discusses the process of creating this consensus summary, how to recommend it, and explains the “worldwide variance of BD/DNC” and “concept of BD/DNC.”

The world consensus on brain death and death by neurologic criteria (BD/DNC) was published in 2020. In this consensus, BD/DNC requires confirmation of deep coma, loss of brainstem reflexes, and apnea, but does not require loss of activity in electroencephalogram (EEG), which is required to determine brain death in Japan. This is because EEG is ineffective in assessing brainstem function. Furthermore, ancillary tests and the use of positive end-expiratory pressure during apnea tests are recommended contents to be included in the Japanese procedure. Considering the current situation in Japan, it is necessary to achieve consistency with the international consensus. The international consensus on brain death criteria was summarized in this manuscript, with differences and concerns compared to the current situation in Japan.

In 2020, the world-consensus of determination of brain death and death by neurologic criteria (BD/DNC) was established. In this consensus, ancillary testing such as cerebral blood flow imaging or electrophysiology testing are recommended when the clinical examination cannot be completed. In this consensus, electroencephalogram (EEG) is not recommended as the ancillary testing for BD/DNC diagnosis since EEG cannot estimate the lack of brainstem function. However, EEG is still mandatory in Japan. The cerebral blood flow tests, such as CT angiography or MR angiography are widely spread in Japan, although these image tests are not recommended as additional ancillary testing due to lack of evidence. The BD/DNC ancillary testing has quite wide variety throughout the world. We thus need to modify the balance between our fashion and international trend on this topic. In this manuscript, the recent international consensus on ancillary testing for BD/DNC diagnosis is summarized, then the knowledge gap and problems on this topic is described.

Extracorporeal membrane oxygenation (ECMO) is widely used in the intensive care unit to treat severe respiratory and/or circulatory failure. Outside Japan, determination of Brain death/Death by neurologic criteria (BD/DNC) and subsequent organ donation under ECMO have been reported. However, as of September 2021, BD/DNC has not yet been formally confirmed for any patient under ECMO in our country. A project to harmonize practice and improve the rigor of BD/DNC criteria has been started and published (Greer DM, et al. JAMA. 2020). Based on this recommendation, we raise the difficulties for determining BD/DNC in patients under ECMO in Japan. Several issues must be addressed before making a first determination of BD/DNC under ECMO in our country. The Japanese protocol for BD/DNC determination should be modified. Performing an apnea test for a patient receiving ECMO requires standardization. Patients whose BD/DNC needs to be confirmed under ECMO will arise in our nation in the near future. It is important to accumulate knowledge on BD/DNC determination under ECMO.

In determining brain death/death by neurologic criteria (BD/DNC) in patients treated with targeted temperature management (TTM), it is important to note that therapeutic hypothermia may temporarily blunt the brainstem reflexes and that therapeutic hypothermia may delay the metabolism of drugs used in TTM, which may affect the BD/DNC determination. The BD/DNC determination should be performed at least 24 hours after the patient has recovered to 36℃ or higher. If sedatives were administered, it is necessary to wait at least five times the half-life of the administered drug after the end of administration.

When organ donation is considered in a clinically brain-dead patient, it is necessary to establish Brain Death/Death by Neurological Criteria (BD/DNC) and continue intensive somatic support to preserve organs for transplantation. Although most management strategies in organ donors are similar to those for critically ill patients, specific pathophysiological changes observed in organ donors include catecholamine surge, neurological lung edema prior to and after BD/DNC, and endocrine complications, such as diabetes insipidus. We summarize the world-consensus statement about brain death and death by neurologic criteria established in 2020 and the current Japanese recommendations and management strategies for five areas, namely, mechanical ventilator settings, catecholamine selection and dosing strategy, choice of antibiotics, management of electrolyte imbalance, and nutrition.

In August 2020, an international consensus of brain death was published. Related to that consensus, this paper outlines issues on children, education, records, religion, and law in comparison with the current situation in Japan. The consideration of children is problematic since BD/DNC is also indicated for neonates according to the international consensus. However, in Japan, the indications are applied to infants for 12 weeks after birth. The education system for physicians to determine BD/DNC（Brain Death/Death by Neurologic Criteria） is not well established. Also, the general public and even the general medical professionals are not educated about brain death and organ transplantation The records of brain-death diagnosis should also include description items for ancillary test. We introduced the checklist prepared by referring to the international consensus. From the perspective of religion, we have to understand various backgrounds and points of views, in order to support patients and their families. When compared with the international consensus, the biggest issue in Japan is whether a patient who is determined to be BD/DNC is considered dead or alive. It is necessary to sort out the problems from each point of view and discuss how to deal with them in Japan.