Original Title: Organdonasjon med bruk av normoterm regional perfusjon hos pasienter som dør av hjerte- og åndedrettsstans når livsforlengende behandling avsluttes

Authors' objectives: Donation of organs from patients with severe brain injury who die after cardiac and respiratory arrest after withdrawal of life sustaining treatment, referred to as controlled Donation after circulatory death (cDCD), has been proposed for use in Norway. The proposed method - cDCD using normothermic regional perfusion (NRP) - is one of several methods under the common designation cDCD. Today's method is referred to as "Donation after Brain Death" (DBD), and means that patients with irreversible cessation of brain function are declared dead while still on mechanical ventilation. cDCD will come in addition to DBD. We conducted a health technology assessment of cDCD’s efficacy and safety, and we considered medical, legal and ethical issues raised by the method.

Authors' results and conclusions: Efficacy and safety We found no convincing difference in organ quality or graft survival after kidney and liver transplantation when comparing cDCD with DBD, because the confidence intervals were wide. We assessed the certainty of the evidence as very low using the GRADE approach mainly because there were few and small studies. Law: No legal barriers performing organ donation after cDCD have been identified. The professional medical community will ultimately be responsible for specifying and formulating a detailed description of death criteria. The description will be crucial for how the law and accompanying regulations are to be understood. The description may be included in a brief or by including more precise provisions in existing regulations. Ethics: A review of the ethical discussion in international academic literature revealed how cDCD has been a subject of debate for many years, particularly in the early phase of establishing the method internationally. Three criteria must be met for cDCD to be ethically sound: 1) The decision to withdraw life-sustaining treatment and the decision to perform organ donation must be separated from each other in a satisfactory way. 2) The premortem interventions must be regarded as very limited. 3) The "Dead Donor Rule" must be adhered to. A fourth criterion requires an ethically sound process for providing information and obtaining consent. The ethical review discusses arguments for and against these criteria are discussed. The conclusion is that with some minor modifications to the cDCD procedure, it will be possible to implement cDCD in an ethically sound manner. Our expert panel agreed about many of the underlying premises needed for the method to be considered ethically sound, but there was disagreement about others. Medical issues: There have been different assessments in the expert panel regarding the death criteria and the interpretation of the wording of law. If cDCD with normothermic regional perfusion is to be introduced, the expert panel believes that the professional medical community must design a more robust quality assurance concerning the death criteria and update the current cDCD procedure. This will include specific neurological tests to evaluate brain function and documentation of ceased breathing when confirming death. Some in the expert panel also believe that further measurement methods in addition to invasive measurement of blood pressure and heart rate should be used to ensure that cardiac arrest is achieved. The criteria proposed by the professional medical community can be stated in a brief or specified in existing regulations.

Authors' methods: We have prepared a health technology assessment that contains three domains: 1. Efficacy and safety including medical issues, 2. Law and 3. Ethics. Inclusion criteria: PICO 1 (P: population, I: intervention, C: comparator and O: outcome): Population: Individuals aged 16 to 60 (or up to 70 years based on individual assessments) with severe brain injury who are in intensive care and who die of cardiac and respiratory arrest when life-sustaing treatment is withdrawn. Intervention: cDCD with normothermic regional perfusion. For all three domains, effect and safety, law and ethics, the population and intervention in PICO 1 are the same. Topics and issues that are considered within law and ethics are described under the respective chapters. Efficacy, safety and medical issues: Inclusion criteria, continued: PICO 1: Outcome: The number of donors, the number of organs (kidneys, pancreas and lungs), and adverse events. Themes highlighted: a) Medical issues related to the diagnosis of death: premortem interventions, detection and assessment of lasting cardiac and respiratory arrest, and autoresuscitation; and b) cDCD guidelines in other countries. PICO 2: Population: recipient of organs from dead donor. Intervention: cDCD with normothermic regional perfusion. Comparison: DBD or cDCD with rapid recovery. Outcome: Deaths, recipient survival, organ function and graft survival. We conducted a systematic search for studies with and without control groups on 11.10.2018 and an update search 07.03.2019. The effect estimate was calculated as the risk ratio (RR) for dichotomous outcomes. We assessed the certainty of the evidence with the GRADE approach. The certainty in the evidence, that is, the degree of confidence we have that an effect estimate is close to a true underlying effect, can be considered high, medium, low or very low. For "Medical issues" and "Guidelines for cDCD in other countries", the results are presented descriptively. The publications are collected from the systematic search, consensus reports, guidelines, reference lists in included studies, procedures, and after input from the experts. Legal issues The specific legal issue considered in this health technology assessment primarily concerns whether the described method for cDCD can be implemented within the existing framework provided by the law and related regulations. Questions that arose during our investigations have revolved around issues related to (1) the life-sustaining withdrawal process, (2) the definition of death, and (3) questions related to information and consent (detailed in the ethics chapter). The section on legal aspects of organ donation from a deceased donor is written according to the standard legal method. It is based on ordinary legal sources: relevant legal text with regulations and preparatory work. In addition, we have used information from the legislative history for the Transplant law of 1973. The work did not present any methodological difficulties or disagreements, as the legal basis is simple and clear. Ethics We have examined most of the written ethics literature in the field and identified what seem to be the most important ethical issues concerning this method based on the number and content of articles. These questions can be formulated roughly as follows: Does the cDCD increase the risk that decisions to withdraw life-sustaining treatment are affected by the prospect of donation? Are pre-mortem interventions in cDCD ethically justifiable? Is the donor in the cDCD really dead (that is - is the Dead Donor Rule adhered to?)? Does cDCD need a whole new consent practice? We have addressed these issues by giving voice to different views and different positions. The ethical evaluation is partly a descriptive representation of the opinions of others: partly a careful weighting of different views and positions of the ethical experts in the expert group, based on their professional judgment, as well as critical input from all members of the expert group.

Project Status: Completed

Year Published: 2019

URL for published report: https://www.fhi.no/en/publ/2019/Organ-donation-with-the-use-of-normothermic-regional-perfusion/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Norway

Organisation Name: Norwegian Institute of Public Health

Contact Address: P.O. Box 222 Skoyen, N-0123, Oslo