3.2.1 Legislation and terminology

MAiD legislation has been discussed in many countries with varying levels of support and opposition.^s8–s13 As of May 2022, 19 jurisdictions in eight countries have legislation permitting “MAiD by intravenous practitioner-administration of lethal substances,” the form of MAiD compatible with ODE (Data S5: Table B1). The main differences arise from the legals structure. Where MAiD is governed by the criminal code, the provider is only exempted from prosecution if MAiD is provided in accordance with appropriate care requirements. Where MAiD is decriminalized, postprocedural overview procedures are usually established. MAiD laws operate in conjunction with regional patient/professional medical treatment legislation to ensure appropriate end-of-life care alongside MAiD provision.

The legal act of practitioner administration of lethal MAiD substances with the intention of ending a patient's life at their voluntary, competent request was introduced in 2001 in the Netherlands, using the term euthanasia.^s14,s15 Historical associations have caused reluctance to use this term universally, resulting in inconsistent use of terminology, with terms often encompassing both patient self-administration and practitioner administration of MAiD substances.^s16 For the purposes of this review, “MAiD” refers to practitioner administration of lethal substances.

3.2.2 Procedural aspects

The aim of the “MAiD-patient care pathway” is a controlled, comfortable, and swift death, accomplished by circulatory arrest after induced acidosis, hypoxia, and cardiac depression, preceded by induced coma.^s17,s18 MAiD legislation generally stipulates “reserved MAiD acts”, which may only be performed by the legal MAiD provider. These are administration of the MAiD substances and death declaration. The Netherlands,^s17 Colombia,^s19 and Spain^s20 have specific national guidelines, whereas other jurisdictions have protocols.^s21–s30 Provision commences with an intravenous coma-inducing drug, followed by a paralytic agent and sometimes a cardioplegic agent. Typical coma inducers are thiopental and propofol. Nondepolarizing amino steroids are used as paralytic drugs and potassium chloride or bupivacaine as cardioplegic drugs.

The MAiD provider must declare death to bring the procedure to its legal conclusion. However, MAiD laws do not stipulate how death should be determined. Under general laws, death declaration is at the discretion of the attending physician.^s31–s35 Where MAiD is governed by the criminal code, death is often required to be certified by a coroner.

The central eligibility criterion in all countries for MAiD is a required “symptom state” (Table 1). One of the main safeguards is that the MAiD provider must obtain and retain autonomous first-person consent following a patient-initiated request (Table 2). Autonomous means voluntary (competent and without coercion), well-considered, and having unbiased information. Information should be provided about potentially burdensome premortal interventions such as intravenous cannula placement and MAiD assessments such as mandatory peer consultation by an unknown independent physician. Moreover, information provision must take account of the narrative aspects of autonomy, so information should be discussed in relation to the patient's expectations, values, and wishes.^s36–s45 Ongoing end-of-life discussions, including ongoing assessment of the validity of the consent and care planning by the MAiD provider, are an important part of quality end-of-life care.^s46–s56 Regulations generally allow for healthcare professionals having conscientious objections to performing MAiD.

3.2.3 Practice

The 2020 incidence of MAiD, including self-administration, was 17 217 (Data S5: Table B2). Underlying medical conditions were predominantly oncological followed by neurological conditions. The practitioner administration mode of MAiD dominates. The time between MAiD induction and circulatory arrest averages 9 min, shortened by 1–2 min with the use of cardioplegia.^{s23,s27,s29,s30} Rare complications relate to venous access problems and the need for a second dose.^{s17,s18,s23,s27,s29,s30}

3.3.1 Legislation and terminology

Organ donation legislation focuses on consent rules, prohibition of organ trade, donor care, premortal assessments, and the obligation to uphold the “dead donor rule,” originally devised in the USA, which states that patients must be deceased at the time of organ retrieval and the act of retrieval cannot be the cause of death.^{s42,s57–s59} DCDD, the donation scenario compatible with ODE, is not provided in Colombia or Luxembourg.^s60–s62

Consent for the DCDD donor pathway must be obtained and retained by an OPO representative and may be given in advance, deemed (via opt-out) or by a surrogate (in the absence of advance or deemed consent). In most jurisdictions, hospitals are required to notify the OPO of imminent deaths where organ donation may be possible.

DCDD is subdivided into uncontrolled (after unanticipated death) and controlled (after anticipated death) circumstances.^s63 The latest DCDD classification refers to controlled DCDD (DCDD-III) as “planned withdrawal of life sustaining therapy with expected cardiac arrest” with the footnote “This category mainly refers to the withdrawal of life-sustaining therapy decision. Legislation in some countries allows euthanasia and subsequent organ donation described as the fifth category.”^s63

Typical controlled DCDD involves unconscious, intensive care patients, with pathologies that have not caused death by neurological criteria, but where further treatment is no longer considered beneficial to the patient.^s64 Withdrawal of life-sustaining therapy is then performed with death as a foreseen but unintended consequence, allowing procurement of organs.^s65,s66 Rare conscious DCDD involves patients who are dependent on life-sustaining treatment but elect to cease treatment and donate their organs.^s67–s70

3.3.2 Procedural aspects

Three “patient care pathways” are distinguished in DCDD, each with their own objectives, ethical justification, practice, stakeholder motivations, and consent procedures as follows: the death pathway leading to the donating patient's death, the donor pathway leading to the donation of the patient's organs, and the recipient pathway leading to organ implantation (Table 3).^s71–s78 It is important to note that the death and donor pathways involve the same dying patient.

While practice varies, withdrawal of life-sustaining therapy is generally initiated in the DCDD death pathway in intensive care or operating room by administration of sedatives/analgesics followed by withdrawal of vasoactive drugs and mechanical ventilation.^s79–s82

The DCDD donor pathway involves premortal interventions for the recipient's benefit. Depending on which premortal interventions the country's legislation permits, these may include imaging, blood tests, invasive arterial blood pressure monitoring, heparin administration, and changing the setting where death takes place.^{s66,s79,s83–s88} Relatively new are postmortal regional perfusion procedures.^{s83,s89–s104}

Death, currently defined as the moment of “permanent death,” must be awaited before organ procurement, to uphold the dead donor rule in the DCDD donor pathway.^{s42, s105–s108} With DCDD, the moment of permanent death is defined as the moment when circulation to the brain ceases following cardiac arrest and chances of spontaneous return of circulation are very small.^s65 Circulatory arrest assessment methods and the wait time after arrest, required to establish “permanent death,” vary internationally (Table 4). Related OPO regulations and targets vary too.^s109–s113

Eligibility for DCDD is mainly determined not only by consent, donor criteria, and logistics but also by jurisdiction-specific circulatory death certification. The OPO representative must ascertain or obtain and retain consent for the DCDD donation pathway.^s59 Where deemed or advance consent exists, this requirement is satisfied.^s66,s114 In its absence, surrogate consent must be obtained from the family.

Premortal interventions and immediate postmortal procedures are justified for the recipient's benefit to optimize donor organ quality.^{s79,s83–s89,s115–s131} However, varying outcomes when evaluating premortal intervention benefit-to-harm ratios result in differences between provisions in different jurisdictions.^{s42,s66,s79,s84–s86,s114,s132,s133} Postmortal regional perfusion is under discussion in some jurisdictions, as it may pose death safeguard challenges or conflict with legal death definitions.^s134–s145 For example, Australian legislation prohibits restoration of any circulation after death.^s141 Healthcare professionals' conscientious objections to DCDD aspects are receiving increasing attention.^s146–s149

3.3.3 Practice

DCDD incidence is increasing.^{s65,s150–s155} The period between starting the withdrawal of life-sustaining therapy and permanent circulation arrest, which determines donor eligibility, varies from minutes to days (47% of DCDD cases meet the commonly applied 2 hours limit for donation eligibility) and is difficult to predict.^{s79–s81,s156–s161} Donation outcomes after DCDD are similar to outcomes following donation after neurological determination of death for kidneys, lungs, and pancreatic islets, but they are more variable for livers and hearts.^{s102,s140,s156,s162–s223}

3.4.1 Legislation and terminology

Current laws do not prohibit ODE, but do not mention the possibility either, and regulatory organs only make cautious statements, such as “Voluntary termination of life by means of euthanasia does not necessarily preclude organ and tissue donation.”^{1, 42, 43} Or, for ODEH, “The committee regards the procedure in principle as a viable route, provided that it does not impede a careful establishment of death.”⁴⁴ This contrasts with the open support of “Right to Die” organizations, patient advocacy organizations, individual patients, and OPOs.^45-55

The requirement for hospitals to notify OPOs of imminent deaths, in general, does not apply to MAiD patients, except in Ontario and Quebec in Canada where this is unclear.^56-58 ODE-derived organs can only be allocated to jurisdictions where MAiD is permitted.⁵³

In 2017, the acronyms ODE and ODEH were coined to refer specifically to the total process that combines MAiD and DCDD, preserving the eligibility assessments and safeguards for both these subprocedures but integrating them in a way that places the emphasis on caring for the MAiD patient and the ethical perspectives and considerations this entails.^{59, 60} This emphasis is what distinguishes ODE from conscious (or unconscious) withdrawal of life-sustaining therapy DCDD/DCDD-III or DCDD-V procedures. ODE should also be clearly distinguished from “living donation in anticipation of MAiD,” which has no regulatory or professional endorsement, and “MAiD by removal of organs in an anesthetized patient,” which constitutes homicide.^61-72

3.4.2 Procedural aspects

The major difference between ODE and typical DCDD-III (or withdrawal of life-sustaining therapy/DCDD) is the MAiD act in the DCDD death pathway, resulting in the foreseen and intended death of a conscious patient in the donor pathway, significantly affecting both pathways. ODEH involves additional deployment of a mobile team and mid-procedure transport.^{73, 74}

The Netherlands published a national guideline, based on a 2-year Delphi-like multistakeholder process organized by the Dutch Transplant Foundation (Table 5). Key considerations were peer-reviewed, published, and presented to the Dutch house of representatives.^{59, 83} The guideline has two parts, consisting of a practice manual and background information, and replaces earlier manuals. It focuses on the MAiD patient in the death pathway during four phases: (1) decision-making about the end of life, (2) preparations for the end of life, (3) end of life, and (4) organ donation and family grief counseling. The 2022 update includes the recommendation for the invasive blood pressure measurement and the ODEH option.

Canada published national policy guidance, based on a 2-day forum organized by the Canadian Blood Services and operating together with existing protocols.^{77, 78, 84, 85} Key considerations were peer-reviewed and published. The primary perspective is the DCDD donor patient pathway, with MAiD regarded as an end-of-life intervention with five steps: (1 + 2) MAiD request and determination of eligibility, (3) OPO referral and DCDD suitability assessment, (4) MAiD patient approach by OPO representative for consent and donor testing, and (5) hospital admission for premortal interventions and MAiD provision. Recent summits were held regarding the 2021 changes to MAiD legislation and the ODEH option.

Belgium published a national DCDD consensus by an expert group, organized by the Belgian Transplantation Society.³⁴ A chapter is dedicated to ODE, with the primary perspective of the donor pathway and focusing on the importance of preserving MAiD patient autonomy. More specific local protocols have been developed.⁸⁶

Spain commenced ODE practice following the legalization of MAiD but has no official publications yet.^79-82

3.4.3 ODEH models

No ODEH guidelines have been published yet, but several models exist (Table 6 and Figure 2). With the Dutch model, an anesthesiologist/intensivist waits near the patient's preferred dying location. The procedure is initiated with midazolam sedation by the MAiD provider, with only the patient and their loved ones present for final farewells. After sedation, the anesthesiologist/intensivist is alerted and converts sedation to anesthesia with propofol, intubation, and the application of tidal ventilation. Subsequent continuous propofol administration is provided during transport and physiological conditions are maintained until MAiD death occurs in the hospital. Premortal interventions are performed in the hospital before MAiD administration. Death declaration by the MAiD provider according to permanent death criteria concludes the MAiD procedure and multiorgan donation follows. If mechanical, ventilated, or organ-perfusion support unexpectedly fails during transport, the MAiD substances are administered immediately, initiating uncontrolled but comfortable death. Three variants have been performed. The first (Dutch-I) variant differs from II and III by the absence of medic/paramedic attendance during farewells, the absence of vital monitoring when the patient is still conscious and subsequent transport with controlled anesthesia (variant III only).

With the Canadian model, a respiratory therapist and a physician wait close to the patient's preferred dying location. After MAiD substance administration at this location, the body is moved to the nearby ambulance, where EKG and apnea are monitored for 5 min. Death certification by the MAID provider and the second physician according to permanent death criteria concludes the MAiD procedure. After intubation and another 5-min waiting period, a nonperfused, in situ lung preservation technique is applied and transport is initiated. At the hospital, lung retrieval is performed.

3.4.4 Eligibility and safeguards

Aside from logistical feasibility, eligibility for ODE/ODEH coincides with eligibility for MAiD and DCDD. The main safeguards involve the independent provision and maintenance of first-person consent for both MAiD and DCDD. To safeguard autonomy, many jurisdictions prohibit or discourage OPO/physician-initiated DCDD consent approaches or directed donation with ODE.^{59, 77, 91-98}

Safeguarding end-of-life experience for MAiD patients in the ODE context requires active monitoring, given the potential for changes to the benefit/harm balance with these, sick, vulnerable patients, unlike unconscious withdrawal of life-sustaining therapy patients. Examples include burdensome assessments during their final days of life, painful interventions, the presence of unknown healthcare teams during MAiD, a different setting for MAiD, changes to the family's experience, and bereavement due to the removal of the body for several hours.^{59, 77, 92, 95, 99-116}

The Dutch guideline incorporates choices about varying levels of premortal intervention burden as an explicit part of the donor pathway consent process, with the patient deciding the level of burden they wish to endure and OPO representatives then deciding which organs can be procured based on the premortal interventions appropriate to this level of imposed burden.⁵⁹ In contrast to the regular approach of presenting premortal interventions and the promise of higher organ yield, this diminishes the risk of insufficiently well-considered compromises to the end-of-life experience.⁵⁹ The Canadian guidance states “Based on their own comfort and preferences over how they wish to spend their last days, they may have questions and decline some investigations or donation interventions.”⁷⁷ With ODEH, some burdens and potential distress are reduced compared with ODE (Table 7).

Reappraisal of the benefit/harm ratios of premortal interventions with ODE led to the removal of the requirement for potentially painful invasive blood pressure monitoring for death assessment in Canada, unlike the Netherlands, where the same discussions resulted in this requirement being re-emphasized.^{44, 77} With ODEH, invasive blood pressure measurement is not burdensome as the patient is unconscious.

Concerns have been expressed regarding the use of sedatives during mid-procedure ODEH transport as, unlike propofol anesthesia, these do not guarantee complete loss of awareness.^{88, 118}

Healthcare providers' conscientious objections are a familiar topic within MAiD care pathways, but less common in DCDD death pathways, typically performed with the less controversial withdrawal of life-sustaining therapy, and jurisdictions are developing protocols for this scenario.^{59, 77}

3.4.5 Practice and donations

By 2021, ODE had been provided 286 times and ODEH 8 times, with the incidence rising annually (Table 8). The main underlying conditions were neurodegenerative and the most common MAiD provider was the general practitioner.

The quality of ODE donor organs is at least comparable to organs retrieved following the withdrawal of life-sustaining therapy/DCDD and even donation after neurological determination of death (Data S4).

This—perhaps not universally anticipated—similarity in organ quality may be due to earlier methodological bias in ischemia assessment, minimal lasting effects of MAiD substances, and underlying conditions and specific—pathophysiologic—effects related to donation after neurological determination of death. Experience with ODEH is limited, but there is no logical reason to assume inferiority.

Since 2005, 1136 organs have been donated, 988 of which were transplanted, to approximately 837 recipients resulting on average in 2.9 recipients receiving organs per ODE patient (Data S5: Tables B3/B4 and Figure 3).

3.4.6 Desirability and appropriate care

Eligibility criteria and safeguards should ensure the highest quality of care with medical procedures. The remaining challenges mentioned in the literature can be characterized as issues of desirability and appropriate care (also called due care).¹³⁶

The first ODE patient from Belgium told her GP in 2005: “I want to donate my organs. That way, I'll still be doing something good with this body of mine.”¹¹⁹ A Dutch ODEH patient expressed the same sentiment in 2017: “I want to donate to be able to do something good with the diseased body that's also leading me to choose euthanasia.”^{48, 89} In 2019, a Canadian ODEH patient explained that “he wanted to save another person's life after seeing so many traumatic deaths on the job (being a policeman),” and an ODE patient “…kept pushing even though she wasn't able to speak (anymore).”^{45, 46} Many more patients have voiced this desire publicly.^{45-47, 52, 137} These patients appear to have a dual perception of their bodies: instrumental as an object for donation and manifesting as a subject in the world.^138-140 This can be reformulated as “the severely diseased body that causes the loss of hope and suffering is, at the same time, a source of something good,” perhaps linked with the idea of a “body project,” indicating the importance of the body as a site for personal preferences and decisions.^{48, 59, 119, 139, 141, 142} Such a “body project” may contribute to the donor's moral identity, in which they see the body as a useful source for others in need, expressing something about their moral character.^{139, 143} For end-of-life care stakeholders, the desirability of ODE coincides with the last wishes of the MAiD patient.^{46, 144, 145} Recipients and their stakeholders welcome the addition of donor organs. Public opinion is still evolving, but a Canadian survey has shown strong support for ODE.⁷⁷ The main concerns about appropriate care center around two issues: the potential for the MAiD decision and the organ donation decision to influence one another and premortal interventions and their effect on the MAiD patient's end-of-life experience in the donor pathway (Data S5: Table B5).

4.1.1 Consent

Resolving the consent issues in ODE starts with the recognition that the death pathway and donor pathway in DCDD involve the same potentially influenceable MAiD patient. There are several reasons why it is inherently impossible to adhere to the strict principle of separation of care pathways, as advocated in the withdrawal of life-sustaining therapy/DCDD practice to minimize the risk of influence.^{91, 96, 110, 146-149} With the withdrawal of life-sustaining therapy/DCDD, an unconscious patient's decision to donate is not subject to influence if deemed/advance consent is present. In its absence, approaching the family to obtain surrogate consent is explored. Besides, within the death pathway, the withdrawal of life-sustaining therapy decisions with an unconscious patient is inherently nonpatient-dependent. The only potential for influence on this decision lies in the interaction between the patient's intensive care team/surrogate decision-maker and OPO representatives.

With ODE, there are multiple opportunities for considerations in one pathway to influence a decision made in the other. Current guidance indicates that the MAiD decision should precede discussion of organ donation and only after consent for MAiD is confirmed may the OPO representative approach the MAiD patient to obtain and retain consent for the donor pathway. But, from that moment on, the potentially influenceable patient (in contrast to the withdrawal of life-sustaining therapy patient) not only decides on providing and maintaining donor pathway consent but also on maintaining the MAID death pathway consent. There is an inevitable intertwining of care pathways and ongoing interactions with the OPO representatives/donor coordinator might influence the donor to maintain consent for MAiD and donation. The MAiD provider needs to understand the dynamics of human decision-making and the inherent psychological processes of altruism and social desirability that could uniquely influence the MAiD consent process in the context of ODE (but not when MAiD is the only consideration).^{146, 150-154}

First-person consent with ODE respects the interests of autonomy better than deemed or surrogate consent. Some ODEH modes enhance this, as patient care pathways do not intertwine on the final day while the patient is still conscious.^{73, 74, 154}

To anticipate the pathway interaction risks, the Dutch guideline advocates minimal contact between OPO representatives and the conscious MAiD patient.⁵⁹ Communication should be confined to providing donor pathway information, without the aim of conversion to ODE or retaining consent for DCDD, and MAiD should not be discussed at all.¹¹¹ With ODE, end-of-life care should remain the responsibility of the primary patient care team. From this perspective, labeling the donor consent process as “end-of-life care” could lead to coercion-sensitive confusion. The Canadian guidance advocates specialized OPO representatives to deal with ODE practice.⁷⁷

4.1.2 End-of-life care

For the MAiD patient in the donor pathway, unlike the unconscious withdrawal of life-sustaining therapy patient, every premortal intervention is potentially burdensome. The literature agrees that for valid donor pathway consent, all premortal interventions for the recipient's benefit must be discussed with the MAiD patient in terms of their necessity and impact on the end-of-life experience, bearing in mind the patient's aims and wishes for the end-of-life experience. Every premortal intervention should be carefully analyzed to establish its benefit/harm ratio. With some ODEH modes, the burden is diminished, as most premortal interventions can be performed while the patient is anesthetized.

4.1.3 ODE guidelines

ODE is an exceptional procedure, presenting legal, ethical, and operational challenges and requiring dedicated guidance that will gain and retain society's confidence. If protocols are diffuse in their aims or burdened by earlier habits and ways of thinking, quality of care could be compromised and trust lost.^{96, 153, 155} Professionals need to recognize each other's different roles and interests and coordination of this should be incorporated in a guidance document. Separate classifications of ODE-related DCDD (DCDD-V) and ODE-related MAiD aid this objective.^{156, 157}

4.1.4 Death

Upholding the dead donor rule and the need for viable organs led to the “permanent” death definition within DCDD. However, permanent does not equal irreversible, leaving a window for rare, undesired autoresuscitation.^158-165 Also, dying sometimes takes longer than expected. From the perspective of the MAiD-patient care pathway, which focuses on swift and comfortable death, the occurrence of delayed death or autoresuscitation would suggest an insufficient first dose and a second dose should follow. In the withdrawal of life-sustaining therapy patient care pathway, focused on ending mechanical, ventilated, or organ-perfusion support when no longer considered beneficial to the patient while preventing discomfort, this occurrence signifies a prolonged dying phase and circulatory arrest (or its return) must be awaited. In the DCDD donor patient care pathway, focused on donor organ care without harming the donor, this occurrence also signifies a prolonged dying phase and death must be awaited (or awaited again) for the dead donor rule to be fulfilled before procurement can commence. Within ODE, the most feasible option in the event of delayed death seems to be for the MAiD provider to administer a second dose of MAiD substances after a predefined fixed period and for the OPO providers to wait for permanent death to occur (or reoccur).

4.1.5 Access

The main limitation to ODE access is the limited number of jurisdictions (19) allowing practitioner-administered MAiD.^{79, 166-170} The MAiD “stopcock infusion procedure,” available in some jurisdictions⁴² and involving the patient self-administering the intravenous MAiD substances, might be acceptable in more jurisdictions as it qualifies as assisted suicide and could be used with ODE.

DCDD access is also limited (17 countries).¹⁷¹ DCDD incidence as a proportion of total deceased donations varies significantly by jurisdiction and further acceptance might increase access.

ODE incidence in jurisdictions permitting MAiD was 37 in 2020, while MAiD incidence was 16 977. With an estimated 10% eligibility, this would put utilization at roughly 2%, possibly due to a lack of familiarity and acceptance, the need for guideline development, and implementation.¹⁷²

Regional ODE access aspects include imminent-death eligibility criteria for MAiD in New Zealand and Australia, the prereview requirement in Spain, and the legal default of self-administration in some Australian jurisdictions.