Donation after circulatory death: a narrative review of current controversies, attitudes, and the evolving role of regional perfusion technology

Introduction

There are two distinct pathways for deceased organ donation today: donation after brain death (DBD) and donation after circulatory death (DCD). DCD was previously known as non-heart-beating donation (NHBD), donation after cardiac death and more recently as donation after the circulatory determination of death (DCDD). DCD is the term in most common use today (1). Patients who might be considered as DCD organ donors are divided into groups known as the Maastricht categories. These were most recently updated in 2013 (Table 1) (2).

DCD is a significant growth area in organ donation. In 2019, DCD donations accounted for 20% of all donated organs in the European Union (EU) (4). Similarly in 2021, it accounted for 30% of donated organs in the USA (5). Despite this increase, DCD has complex ethical, cultural and legal aspects which have limited its introduction worldwide, despite expert society endorsement (6-16).

Organ utilisation rates (OURs) are lower with DCD. In the UK, an average of 3.6 organs are transplanted per DBD donation, compared with 2.1 organs after a DCD donation (17). Similar figures are reported in Switzerland (3.5 vs. 2.3) (18).

DCD has limitations from an organ quality perspective. DCD organs suffer a period of hypoperfusion known as the warm ischaemic time (WIT). Hypoperfusion is most damaging at systolic blood pressures below 50 mmHg: the onset of the functional WIT (fWIT) (Table 2).

As a result, DCD organs are prone to early graft dysfunction, increased reintervention rates and frequently have inferior outcomes when compared with DBD organs. Livers are predisposed to vascular stenosis, ischaemic cholangiopathy and consequently, increased costs (22). Delayed graft function (DGF) in kidneys is significant and patients remain longer in hospital (23).

Despite warm ischaemic injury, outcomes from DCD lung transplantation are encouraging with equal primary graft dysfunction, acute rejection rates and mortality reported (24,25). These results are supported by a systematic review of 17 studies from Europe, the USA and Australia. This said, airway anastomotic complications were twice as likely to occur in DCD lungs (DCD 8–29% vs. DBD 4–14%) (26). While DCD cardiac transplantation also has been successful, either in-situ or ex-situ perfusion is an essential prerequisite to implantation. Studies of DCD simultaneous pancreas-kidney transplants have demonstrated almost equal outcomes to DBD pancreas transplant. However, it is likely that many more pancreas transplants could be performed if the maximum WIT could be extended (27,28).

Where the time from withdrawal of life-sustaining therapies (WLST) to cardiac arrest (known as the withdrawal time) exceeds that set by the transplant team, the process of DCD is stood down. This is reported in up to 25% of DCD attempts in the USA and 40% of DCD attempts in the UK (5,17) (Table 3). An attempted but non-progressing DCD can discourage those involved from pursuing the process in the future. Terms including “waste” and “loss of valuable organs” have been used by donor families. Healthcare professionals have used the expression “a second loss” to describe the experience of families when the process is stood down (29).

In contrast to DBD, estimates of flow and perfusion are not possible during the rapid retrieval operation typical of DCD. Time pressures during the retrieval operation may predispose to organ injury. In context, a reticence to transplant organs where there are legitimate concerns about the degree of ischaemic or mechanical injury is understandable.

The objectives of this review are multiple. Firstly, we aim to examine areas of discourse and obstacles to the wider adoption of DCD with particular emphasis placed on terminology and language. We examine reasons why DCD has been slow to gain momentum and present two areas where international variation is evident: the time of death and the case for antemortem heparin.

Secondly, we present the options for organ preservation in DCD: in-situ cold perfusion (ISP), super-rapid retrieval (SRR) and the most recent evolution of practice—normothermic regional perfusion (NRP). We provide a summary of consensus guidelines and a synopsis of evidence on the use of NRP.

Thirdly, we briefly discuss the preservation of DCD organs using ex-situ technologies. Finally, we discuss ethics particular to NRP, namely antemortem cannulation, post-mortem cerebral isolation and the prevention of collateral perfusion of the brain.

Similar publications individually cover at least one of these four facets in detail (30-32). The target audience are healthcare professionals, from those with a superficial knowledge of DCD to those in Intensive Care Medicine or Transplantation and people in a position to implement change within their own organisation. We present this article in accordance with the Narrative Review reporting checklist (available at https://amj.amegroups.com/article/view/10.21037/amj-23-65/rc).

Methods

We performed a database search as outlined in Table 4. Two reviewers assessed each article. The articles selected and summarised in Tables 5-7 deal with outcomes primarily from liver and kidney transplantation. The references section of each article was accessed and relevant articles examined for inclusion. General outcome measures of organ transplantation were retrieved and summarised, including DGF, primary non-function (PNF), OUR together with graft and patient survival. Delayed post-transplant complications of liver transplantation such as cholangiopathy, ischaemic type biliary lesions (ITBLs) and vascular complications are included. Websites of learned bodies and organ donor organisations were accessed where we sought position and consensus statements. These learned bodies included the Society of Critical Care Medicine (USA), the Intensive Care Society (UK), the Australian and New Zealand Intensive Care Society (ANZICS) and other international transplantation societies.

Language, attitudes and controversies in DCD

Language and attitudes around DCD

The role of language and terminology is an important and perhaps underappreciated area; the language surrounding DCD in particular must be identified and managed. In one study, healthcare professionals experienced in both DBD and DCD were presented with a series of terms and words with positive and negative connotations, significantly more negative words were ascribed to the practice of DCD (65). Terms such as “controlled” and “uncontrolled” populate DCD literature, yet who would wish to be involved in an “uncontrolled process”? In DCD, the terms “controlled” and “uncontrolled” are used, not as a measure of clinical coordination, but rather to reflect applicable time constraints for authorisation or consent and the logistics of organising retrieval teams.

Futility, in reference to further medical treatment, is inextricably linked to the process of DCD however the term itself should ideally be avoided. The word futile may be misinterpreted by relatives to reflect a lack of empathy on the part of the medical professional.

Care is never “withdrawn”, the focus of care is redirected towards palliative measures to allow, insofar as is possible, natural death to occur. Irregular or partially obstructed breathing, frequently referred to as “agonal”, is evident is some patients. This does not necessarily mean patient distress and this word is best avoided.

Healthcare professionals must be careful in how they present the case for DCD, how the topic is introduced and the timing of such an approach. Professional bodies recommend a period of separation between informing families that end-of-life care is appropriate and discussions about the potential for DCD. Where NRP is contemplated, terminology such as “extracorporeal membrane oxygenation”, “resuscitation” and “reanimation”, must be considered carefully before use. Others favour the terms “in-situ tissue perfusion” or “dynamic in-situ organ assessment” (66).

There are aspects of DCD which may negatively influence healthcare professionals’ attitudes. Maastricht “category V” is included in many classifications. This is organ donation following medical assistance in dying (MAiD), organ donation after euthanasia (ODE) or voluntary assisted dying (VAD). While most pathways are characterised by the requirement for patient-initiated request, first-person consent and periods of reflection, many healthcare professionals express unease with these processes (3).

Some transplant professionals argue that controlled DCD (cDCD) may represent a shorter path for intensive care clinicians to follow rather than spending time to determine if brain death will ensue. This is termed “substitution”, and while a valid concern, it is rarely the case. In cDCD, the determination of medical futility is based on clinical examination, radiological investigations and electroencephalographic investigations. Given the scope of investigations required, a significant time may have elapsed before a decision to WLST is reached. An international collaborative of clinicians recommends delaying WLST for a period of 72 hours to improve prognostication. This time will determine the trajectory of the patient’s neurological condition (67).

Defining death and what is reversible

It is important to consider opinions from those opposed to DCD; their criticisms can only serve to develop a more comprehensive understanding for all. The German Medical Association guided by the German Ethics Council have repeatedly rejected the concept of DCD (68). They state that while the diagnosis of brain death is definitive, they argue that DCD involves unacceptable uncertainty.

In Maastricht categories I and II [uncontrolled DCD (uDCD)]: when does irreversible become completely irreversible? While informed by protocols and expert opinion there cannot be complete certainty that resuscitation becomes irreversible at even 30, 60 or 90 minutes.

In Maastricht category III (cDCD): when can medically administered therapies to sustain life be deemed inappropriate with absolute certainty? After how many minutes of circulatory arrest is it appropriate to diagnose death and proceed with organ donation? And finally, could the decision to withdraw life sustaining therapies be influenced in any way by the potential for organ donation?

The uncontrolled categories of DCD (Maastricht categories I and II) have been criticised because of contention around the appropriate duration of resuscitation. The European Resuscitation Council suggest cardiopulmonary resuscitation (CPR) for 90 minutes following arrest where pulmonary embolism is suspected and thrombolytics administered (17). In the era of extracorporeal CPR (eCPR), emergency percutaneous coronary intervention and advanced resuscitation techniques, clinicians must continuously appraise the evidence to avoid the premature termination of resuscitation (29). In later publications, the same authors and others argue that in the setting of failed eCPR, that eCPR and uDCD protocols may coexist and complement each other (18,30).

In cDCD (Maastricht category III), the potential for premature WLST is a frequently cited as an area of concern. Decisions to redirect therapy towards end-of-life care are not made lightly. The UK Donation Ethics Committee recommends two doctors, one a consultant and a second senior doctor, make the decision that further active treatment is no longer of benefit to the patient (69). The Irish National Guideline stipulates that this decision is made by at least two intensive care consultants and a third consultant whose speciality is neurological, such as a neurologist, neurosurgeon, or stroke physician (6). Therefore, at least three consultants and frequently four must reach consensus before consideration is given to DCD. Clinicians involved in caring for these patients at the end of life are not transplant professionals and there is separation between of end-of-life care and transplantation.

The German Medical Association emphasises the importance of confidence and trusts in the medical profession. Although this is certainly important, medical professionals also have a responsibility to pursue change where it may yield benefit for patients. Clinicians are best placed to collate and examine the evidence and in partnership with legal professionals, propose changes to the law if needed (68,70). Decisions regarding the acceptability of DCD in any jurisdiction must be led by medical professionals and have substantive input from ethics, law, and lay members.

In several ways DCD is a straightforward process, and with over 50 years of experience it is a proven concept. The knowledge surrounding the diagnosis of death is explicit and variability in the conduct of DCD is not desirable, hence the importance of national and international consensus documents. Confidence and trust in the system of organ donation is promoted by clarity of the processes involved and the knowledge that the process has been subject to scrutiny (71).

The diagnosis and time of death

The diagnosis of death must satisfy the criterion of permanence. An accepted definition from an expert panel is:

“Death is the permanent loss of capacity for consciousness and all brainstem functions. This may result from permanent cessation of circulation or catastrophic brain injury. In the context of death determination, ‘permanent’ refers to loss of function that cannot resume spontaneously and will not be restored through intervention” (36).

One criticism of DCD is the variability in time periods before death is diagnosed. This inconsistency arises due to concerns around the potential for autoresuscitation (Table 8).

The word “irreversible” frequently appears within definitions of death. “Irreversible” may mean:

• The loss of function that cannot be restored now or at any time in the future, or
• The loss of function that cannot be restored by those present at the time, or
• The loss of function that will not resume and will not be restored.

In the context of DCD, once the period where autoresuscitation is possible has passed, and provided that no attempts will be made to restore circulation as in (III), then the permanence criterion has been satisfied and death may be diagnosed.

ANZICS describe death as a “process” where cellular and organ functions progressively cease:

“The determination and certification of death indicate that an irrevocable point in the dying process has been reached. The precise time of death is somewhat arbitrary and represents a societal consensus that is informed by biological understanding” (16).

While similar to the statement from the expert panel review (above), the word “irrevocable” in context defines the time beyond which autoresuscitation is possible.

In 2023, the Canadian “brain-based definition of death” and the criteria for its determination were published. The scope of the guideline is to include all potential organ donors who will undergo death determination by circulatory criteria or by neurological criteria. The “brain-based diagnosis of death” unifies circulatory death and brain death on the basis of an absent circulation causing the permanent cessation of brain functions. The unified brain-based criteria stipulate that death may result from cessation of blood circulation to the brain after circulatory arrest and/or from devastating brain injury (73,74).

This has significant implications in terms of in-situ establishment of a regional circuit of warmed blood post-mortem, in other words, the permissibility of NRP. In Australian law, circulatory death is diagnosed after the circulation stops and if a circulation is started (including via a regional perfusion circuit) then the patient is no longer dead legally, therefore NRP is not permitted at present (75).

While there are legal, ethical, cultural and religious aspects to the diagnosis of death, there is an inextricable link between circulation and neuronal function. After 20 seconds of circulatory arrest, the electroencephalogram (EEG) becomes isoelectric, the biological events that follow are subject to the potential for resuscitation and the intentions of bystanders. Once the time where the potential for autoresuscitation has elapsed, then neuronal function may only be re-established by creating a circulation. Therefore, the exact time that death is diagnosed is dependent on the clinical setting (76).

cDCD

Autoresuscitation following WLST is extremely rare. The largest prospective observational study involved 631 patients. Clinically reported resumption of cardiac activity (an arterial pressure of at least 5 mmHg), respiratory movement, or both confirmed by waveform analysis occurred in 1% of the sample (5 patients). The longest duration of pulselessness before resumption of cardiac activity was 4 minutes 20 seconds (77).

In an updated systematic review by the same investigators, the measured incidence of autoresuscitation in cases of WLST with or without DCD was 1.8% (19 of 1,049 patients). The principal recommendation from this review was that a 5-minute observation period is sufficient for cDCD, a view supported by most clinicians (Maastricht category III) (78).

uDCD

Autoresuscitation has been described in situations of failed resuscitation after up to 10 minutes. Therefore, in Maastricht categories I and II, it is reasonable to ensure a period of 10 minutes of circulatory arrest has elapsed before death is diagnosed (77).

The case for antemortem heparin

The administration of antemortem heparin in DCD must be considered in context. A medication which provides no direct benefit to the donor patient may be considered “not in their best interests”. However, “best interests” may extend beyond the patient’s medical needs:

“Best interests must also include their social, emotional, cultural and religious interests, so if a patient wished to donate their organs, it would be in their best interests to ensure that the organs are transplanted in the best possible condition” (79).

The UK Donation Ethics Committee called for further work to determine if the use of ante-mortem heparin should be revisited, objections were legal in nature. It stated that there is no ethical barrier, provided an individualised risk assessment is completed (69). In the UK, antemortem heparin is administered to Maastricht category IV donor patients (80).

The Australian Organ Donation and Tissue Authority national protocol and the National Health and Medical Research Council support antemortem interventions providing there is no legal impediment, and state that they support:

“Administering heparin [e.g., 25,000 units (or 300 U/kg)] to prevent small-vessel thrombosis —[however] if there is any concern than heparin may foreshorten the patient’s life, the heparin can be given when the patient is apnoeic.” (16).

In 2013, the American Thoracic Society, the International Society for Heart and Lung Transplantation and the Society of Critical Care Medicine deemed the administration of antemortem heparin ethically acceptable once the risks and potential benefits were disclosed (10). The American Association of Thoracic Surgery 2023 expert consensus document states (in relation to adult cardiac transplantation) that in DCD:

“Administration of intravenous heparin at the point of the WLST is the current standard of care. There are no reported cases of heparin administered at this time hastening death” (81).

In summary, although there is no benefit to the potential donor patient, the principle of non-maleficence must also be considered. Antemortem heparin decreases the incidence of PNF of liver grafts and the rate of vascular thrombosis in pancreatic grafts (82,83). Beneficial effects in other organs are less clear, but may include improved machine perfusion (MP) indices and less glomerular microthrombi in renal transplant and less pulmonary thrombi in lung transplantation.

The evolution of organ preservation

Organ preservation techniques used in DCD

Four techniques are used to minimise the ischaemic injury suffered by organs after circulatory death.

ISP

Cold perfusate is flushed into the femoral artery though a double balloon triple lumen catheter. This localises perfusion to the abdominal organs, a venous vent drains the effluent. Rates of flow are reduced as the venous effluent becomes clear. In practice, this technique is limited to uDCD (Figure 1).

Figure 1 In-situ cold perfusion.

SRR

The flow diagram outlines the process from WLST until laparotomy (Figure 2). At the end of a limited period of organ ischaemia, this technique involves a rapid laparotomy, isolation of the inferior vena cava (IVC) and aorta and immediate cold flushing before recovering the organs.

Figure 2 Schematic for cDCD—rapid retrieval. SBP, systolic blood pressure; SpO₂, oxygen saturation; cDCD, controlled donation after circulatory death.

NRP

In the context of DCD, NRP is an enhanced therapy, delivered post-mortem which ameliorates the effects of ischaemia on donated organs (Figures 3,4). Regional perfusion may be limited to the abdominal-NRP (A-NRP), or to thoraco-abdominal-NRP (TA-NRP). The focus of this paper is the use of A-NRP in cDCD (Maastricht categories III and IV).

Figure 3 Schematic highlighting time-periods for cDCD with NRP. fWIT, functional warm ischaemic time; SBP, systolic blood pressure; SpO₂, oxygen saturation; cDCD, controlled donation after circulatory death; NRP, normothermic regional perfusion.

Figure 4 Circulatory path for abdominal-NRP (cDCD or uDCD). Low pressure points in proximal aorta. (A) Endovascular aortic occlusion balloon & low-pressure aortic point via wiring lumen of catheter. (B) External aortic occlusion with cross-clamp & low-pressure aortic point via arch cannula. cDCD, controlled donation after circulatory death; uDCD, uncontrolled donation after circulatory death.

NRP has the potential to increase the time-period from WLST until organ donation begins by several hours. If the timer starts with the onset of fWIT, and NRP is used, then it is likely that less stand-downs will occur. The number of organs retrieved per patient are higher than with standard DCD (3.3 vs. 2.6) (38). While on NRP, macroscopic appearances and trends in biochemical parameters provide reassurance of post-transplant function.

Ex-situ MP technologies

Normothermic MP (NMP) and hypothermic oxygenated perfusion (HOPE) modalities enable ex-situ organ assessment. These machines are portable and facilitate organ transport with ongoing artificial nutrients and oxygen perfusion. Several trials have demonstrated comparable outcomes for A-NRP and NMP liver transplants where graft dysfunction and OUR are examined (84,85). In heart transplantation, the direct procurement protocol and MP (DPP-MP) strategy has yielded equal outcomes to a matched cohort of DBD heart donors. In the USA, 80% of DCD heart donors are retrieved by DPP-MP (86), this is also the current standard in Australia and the UK (87).

While ex-vivo technologies are ethically less problematic, expense is significant; the cost of disposables for the NRP circuit is $4,000 USD, while the Heart OCS™ (Transmedics, Inc., Andover, MA, USA) averages $46,000 USD (88).

NRP

Evidence for the use of NRP

Protocols, process and outcomes of NRP in the context of DCD are widely published (22,33-36,67,72,89-95). Online webinar series are available from the European Society of Organ Transplantation and the Organ Donation Alliance (12,96). The use of NRP is evidence-based and supported by individuals and expert groups in numerous reviews and consensus statements (Table 5).

The importance and contribution of perfusion repair is supported by an international group from the USA, the UK, Canada, Australia and other European centres (67).

“The value of perfusion repair… is established by this consensus statement to recommend that a protocol of cDCD utilise either in-situ or ex-situ perfusion consistent with the practice of each country conducting cDCD”.

The evidence for the use of NRP in DCD is supported by review and consensus articles (Table 5) in both cDCD (Table 6) and uDCD (Table 7). NRP allows time for the close inspection and viability assessments of perfused abdominal organs. It permits the elective recovery of organs and reduces the potential for organ damage as a consequence of the SRR technique.

While the economic case for the adoption of NRP has been proven in the context of hepatic transplantation, ultimately, some commentators suggest the economic case for NRP could be championed by the renal allograft experience (41,79,94).

Benefits of NRP

Reduced DGF in renal transplants

Earlier improved renal graft function will decrease hospital stay and the sustained improvement in glomerular filtration rate will lead to longer graft function in recipients.

Improved outcomes from hepatic transplantation

Previously, rates of ischaemic cholangiopathy seen in DCD have been major deterrents. NRP ameliorates the damaging effects of warm ischaemia and outcomes seen with DCD-NRP approximate those seen with DBD. Consequently, the Spanish Liver Transplant Society and the International Liver Transplant Society both recommend NRP in DCD liver transplant (34,97).

DCD lung transplantation

There has been concern that the adoption of A-NRP may impede lung retrieval, or will lead to a reduction in the number of lungs retrieval in DCD. While technically more complex, A-NRP and lung retrieval in DCD may be combined; a dual hypothermic thoracic and normothermic abdominal approach may be the technique of choice. Reports from Spain have demonstrated similar outcomes when compared with DBD donors (24,38,51,98).

Where lung retrieval is contemplated using TA-NRP, anterograde perfusion will not be possible until the heart begins beating (67). Despite this, demonstrated outcomes have been excellent albeit with small numbers (n=26) (99).

Essential components of an NRP protocol

Multiple NRP protocols are available online, which vary depending on their country of origin (72,95,100-102). The development of an institutional and national protocol for NRP is a difficult process. The agreement of key stakeholders in transplant surgery, transplant medicine, intensive care medicine, legal professional bodies and the broader medical community is an essential step. One or more bodies may be charged with the application of professional standards and accreditation based on guidelines, quality assurance, audit and governance.

The separation and professional independence of intensive care medicine and transplantation is of paramount importance. Specific aspects of intensive care unit (ICU) management include the location of end-of-life care, the WLST, acceptable antemortem interventions, diagnosing death and preparation of the patient following death. In all protocols there is a specific focus on ischaemic times, with a strong emphasis on go and no-go timepoints.

Adopting NRP is likely to result in significant baseline capital expenditure. There are additional ongoing costs of funding rotas, recruitment and training. In the UK, specialist training and certification is required for the role of Advanced Perfusion and Organ Preservation Specialist (APOPS), an individual central to the success of NRP (101).

Specific ethical considerations in NRP

A significant number of DCD attempts do not progress to organ donation as patients may not die within the timeframes outlined. End-of-life care may be a significant stress for medical and nursing staff, and, where time constraints are involved in the context of organ donation, an attempted but non-progressing organ donation can discourage future attempts (29). NRP significantly decreases these time constraints. While there are several contentious areas, we focus on two: patient cannulation and the potential for residual flow where the cerebral circulation is not adequately excluded.

Postmortem cannulation

Patient cannulation for the purposes of A-NRP may be achieved post-mortem via femoral or central vessels. In A-NRP, the aorta and IVC are exposed and cannulated at the point at which they bifurcate in the lower abdomen. In TA-NRP, the thoracic aorta and right atrium are cannulated in the chest.

Antemortem cannulation

There is a balance between what antemortem cannulation can offer and the risks it poses to the patient. International practice varies considerably regarding the permissibility of cannulation in the setting of cDCD. Some jurisdictions are completely opposed, while others such as Spain allow complete cannulation for A-NRP antemortem. In other jurisdictions, a more nuanced approach is adopted: vessel localising cannulas are placed in the femoral vessels antemortem, these are then upsized after death. It could be argued that there is merit and dignity for the potential organ donor patient where successful postmortem femoral cannulation is guaranteed, therefore avoiding a rapid cut-down or pressurised laparotomy. This then allows a slow and careful dissection for organ retrieval.

Peripheral cannulation: antemortem vessel localisation for percutaneous femoral cannulation

Placing two sheaths using local anaesthesia, ultrasound and micropuncture techniques will minimise pain and discomfort. The sheaths are then covered with a sterile dressing. These cannulas do not require patient movement or X-ray confirmation and may be removed with minimal discomfort if DCD is stood down.

In 2019, an ethical evaluation on the use of A-NRP in cDCD was conducted by the Norwegian Institute of Public Health. It was their assessment:

“that the antemortem insertion of thin cannulas into the femoral arteries and veins does not deviate from good patient care or differ in ethical terms from practices adopted to support DBD.” (102).

Others argue:

“there is a certain amount of intellectual strain involved in thinking antemortem interventions [are] motivated by a concern for the best interests of the donor”;

“While antemortem interventions may promote an autonomous wish to donate organs, critics worry that this may come at the cost of causing deontological harm.” (103).

Echoing the case for antemortem heparin, discussions return to an interpretation of patient’s best interests. The patient’s beliefs, values, and social, cultural and altruistic interests should be considered alongside their clinical interests (79,104,105).

Preventing reconstitution of the cerebral circulation

In the period following death, the principle of permanence mandates that there must be no flow of blood outside the limited NRP circuit. This must be absolute. Escape of blood outside of the oxygenated circuit and into the cerebral circulation risks the potential for nociception (106). Pressures within the abdominal aorta during A-NRP are 38–65 mmHg, while pressures above the aortic occlusion balloon are 5 cmH₂O (3 mmHg) or less.

A second area of concern in A-NRP is the potential escape of oxygenated blood through small collateral circulations. Theoretically, blood might travel via a series of anatomical connections to reach the central nervous system (CNS).

Whether the escape of blood from an abdominal NRP circuit could result in a return of spontaneous cerebral and cardiac activity (ROSCCA) is important. One systematic review addressed this question in 484 donor patients in 12 case series (58). In 472 patients the aorta was occluded by an aortic balloon and in 12 cases by aortic cross-clamp, the authors concluded:

“There is no evidence to suggest that ROSCCA may occur following the institution of A-NRP in DCDs where the proximal aorta has been occluded.”

In TA-NRP, despite ligation of the carotid and subclavian arteries, small amounts of blood flow have been demonstrated to drain from the distal ligated ends of these vessels. The recommendation is that the cranial end of each vessel is opened and allowed to drain freely.

The diagnosis of death is contingent upon the absence of cerebral circulation and the prohibition of any intervention which could potentially cause a resumption of cerebral blood flow. Concerns that NRP could invalidate the diagnosis of death have been raised by the American College of Physicians. In particular, concerns have been raised in cases of TA-NRP where the heart may be restarted once the cerebral circulation has been disconnected (107). Some argue that the surgical ligation and exclusion of the carotid and vertebral arteries makes the surgeon complicit in the patient’s death. Other authors refute these assertions and argue, where the patient has been diagnosed with cardiocirculatory death, this diagnosis stands once the cerebral circulation has been isolated:

“the act of clamping the cerebral circulation, occurs after death and so it does not bring on death”;

“Restoring the function of the heart through an ECMO circuit is not autoresuscitation or resuscitation of the person”… [it provides];

“mechanically assisted circulation to maintain perfusion and oxygenation of organs for transplantation” (73,74,106,108-114).

Commentators on the brain-based definition of death add that the circulation of the brain is the foremost concern and state:

“Provided brain function has ceased before initiation of NRP, ligation, occlusion, or transection [of the aortic arch vessels] do not induce cessation of brain function they maintain it.” (114).

The prohibition of manoeuvres which might cause a resumption of cerebral blood flow are the bedrock upon which the diagnosis of death by circulatory criteria is based, i.e., the principle of permanence. Yet, if circulation is re-established by NRP, could this diagnosis of death be retrospectively invalidated? The brain-based concept of death effectively answers this question in stating that the relevant circulation which must have ceased permanently is the circulation to the brain:

“If NRP is effectively restricted to ensure no circulation to the brain, thereby preventing brain perfusion and function, NRP fulfils the requirements of donor death determination and respects the dead donor rule.” (74).

A-NRP is seen by many authors as an option less likely to cause collateral perfusion than TA-NRP because the thoracic aorta, internal thoracic and intercostal arteries are excluded. Surgical ligation of lumbar vessels and the ligation of the femoral vessels exclude superficial epigastric flows (58).

In A-NRP where an endoclamp or aortic occlusion balloon is used, the wiring lumen of the endovascular balloon catheter provides a monitoring port for pressure. This lumen opens outside of the NRP circuit and may be opened to atmospheric pressure. In open surgical cannulation, the aorta is most frequently occluded by an external aortic cross-clamp. A line placed in the supradiaphragmatic aorta above this cross-clamp is then left open to atmospheric pressure. Both “flow diversion” lines act as the lowest pressure point in the body, expected pressures above the aortic balloon or external aortic clamp are less than 5 cmH₂O or 0–3 mmHg (Figure 4) (80,106).

In both situations, first—failure of the external or internal aortic cross-clamp and second—collateral circulations, an aortic arch pressure less than 5 cmH₂O provides a central sump or low pressure point in the circulation. Where doubt exists about the integrity of the cross-clamp, or excessive blood is emitted from the flow diversion line, A-NRP must be discontinued and cold perfusion commenced. These recommendations are consistent with, and satisfy the requirements of, the UK National protocol for A-NRP (80).

Conclusions

DCD can be a challenging process, but organ donation has helped many families gain solace from knowing that the altruistic gift of their loved one is helping others. While protocolised therapy has its place, the adoption of NRP must be in the context of the team, the protocol, the equipment, the oversight, audit and governance. We see NRP as a significant area of improvement in DCD. In many respects it reduces stress for all involved, reducing time constraints in the ICU, reducing the pressure on surgeons to rapidly retrieve the organs and reducing the risk of graft dysfunction in recipients.

In France, Italy and Norway, A-NRP has become the standard organ retrieval procedure for DCD donors mandated by the health authorities. It is the preferred procedure in several regions in the UK and Spain. The function and outcomes after kidney and liver transplantation using NRP appear superior to non-A-NRP DCD.

The future of organ donation may comprise a suite of technologies to include in-situ perfusion-NRP and ex-situ perfusion devices such as the OCS™ (Transmedics) device for cardiac support, mobile ex-situ lung perfusion and the OrganOx (Oxford, UK) machine for ex-situ liver perfusion. While each of these technologies has something to offer, perhaps NRP offers most in terms of ameliorating ischaemic injuries to several organs simultaneously. Although TA-NRP has hurdles to overcome before gaining widespread acceptance, the adoption of A-NRP is an easier route in the short-term.

The authors acknowledge the limitations of this review, there are a notable lack of prospective randomised trials concerning the use of NRP and other ex-situ technologies. Previous meta-analysis has commented on the heterogenous nature of many studies. Each included study was at the discretion of the authors and may not represent a thorough quality analysis of each paper. While we acknowledge the obstacles, the evidence supports the more widespread adoption of NRP.

Acknowledgments

Funding: None.

Footnote

Peer Review File: Available at https://amj.amegroups.com/article/view/10.21037/amj-23-65/prf

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://amj.amegroups.com/article/view/10.21037/amj-23-65/rc

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://amj.amegroups.com/article/view/10.21037/amj-23-65/coif). J.O.R. is a clinical lead in organ donation and a national clinical lead for Donation after Circulatory Death (DCD). He is member of the advisory board of the Organ Donation Transplant Ireland (ODTI) – The National Organ Donation and Transplant Advisory Group (NODTAG), this is not a paid role. He provides clinical support to donor coordinators within the national organ procurement service. Standard on-call rates of pay apply to this role. J.O.R. serves as an unpaid editorial board member of AME Medical Journal from January 2023 to December 2024. A.G. is a clinical lead in organ donation and works closely with Organ Donation and Transplant Ireland (ODTI). Part of his role consultant’s salary is supported by ODTI. He provides advisory to the ODTI in areas such as of strategy, education, and planning. He provides clinical support to consultants in other hospitals in areas relating to organ donation and transplant. He is a member of the advisory board of the Organ Donation Transplant Ireland – The National Organ Donation and Transplant Advisory Group (NODTAG). He is the national lead for the potential donor audit. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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