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Uncontrolled Donation After Circulatory Death: A Unique Opportunity

Coll, Elisabeth MD, PhD1; Miñambres, Eduardo MD, PhD2; Sánchez-Fructuoso, Ana MD, PhD3; Fondevila, Constantino MD, PhD4; Campo-Cañaveral de la Cruz, José Luis MD, PhD5; Domínguez-Gil, Beatriz MD, PhD1

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doi: 10.1097/TP.0000000000003139
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Abstract

INTRODUCTION

Organ transplantation represents the best, if not the only, therapeutic option for patients with end-stage organ failure. However, the inability to properly satisfy the needs of patients limits the full expansion of transplant therapies. In 2017, almost 140 000 solid organ transplants were carried out in the world,1 an activity that barely covered 10% of a global need that is expected to increase.2 Meeting the demand of organs for transplantation is further challenged by the declining incidence of brain death that has been described in some settings.3

Donation after circulatory death (DCD) re-emerged during the 90s as a promising option to expand the donor pool.4 While controlled DCD (cDCD) refers to donation from patients who die following the decision to withdraw life-sustaining treatments that are no longer deemed beneficial to the patient, uncontrolled DCD (uDCD) is defined as donation from persons who die following an unexpected cardiac arrest (CA) that is unsuccessfully resuscitated.5 The modified Maastricht classification of DCD donors defines this type of donation as category II, and further subclassifies it into category IIa, if the CA preceding the donor’s death occurs in the out-of-hospital setting, and IIb, if it occurs within the hospital.6 This distinction is due to the different duration of warm ischemia and profile of potential uDCD donors depending on where the CA occurs.

uDCD is developed in a reduced number of countries, mostly in the European setting (Figure 1).7,8 Quantitatively speaking, the most successful programs have been developed in France and Spain (IIa), and in Russia (IIb). Of note, the number of uDCD donors and associated transplant procedures have been declining over time in the most developed European programs, after reaching a maximum back in 2010 (Figure 2). The limited number of uDCD programs is surprising given the straightforward recommendation of the European Resuscitation Guidelines, that uDCD should be considered when advanced cardiopulmonary resuscitation (aCPR) is terminated.9 It is also surprising given the large potential for uDCD. In 2006, the Institute of Medicine estimated that uDCD could increase the potential donor pool in the United States by 22 000 cases each year and urged for the development of this kind of programs.10 However, as of today, uDCD has not been successfully implemented in this country.11 The European Registry of Cardiac Arrest (EuReCa ONE) study monitored all cases of witnessed out-of-hospital CA attended by emergency medical services (EMS) or a bystander in 27 European countries during 1 month. Out of 7146 identified cases, return of spontaneous circulation (ROSC) was achieved in 28.6%.12 The study hence revealed a large unrealized potential for uDCD. However, more refined assessments of the potential for uDCD show that, of patients suffering a CA with no ROSC, many fail to fulfill the selection criteria to be considered potential uDCD donors.13-15 Still, the potential contribution of uDCD to donation and transplantation activities can be substantial.

FIGURE 1.
FIGURE 1.:
European countries that have developed at least 1 uncontrolled donation after circulatory death (uDCD) procedure during 2008–2018 (Austria, Belgium, France, Israel, Italy, Latvia, Lithuania, Poland, Portugal, Russian Federation, Spain, Switzerland, The Netherlands, and United Kingdom) and number of uDCD donors during that period of time. Source: Unpublished work from Lomero M, Lomero M, Gardiner D, Coll E, et al. Donation after circulatory death today: an updated overview of the European landscape. Transpl Int 2019 Sep 3. doi: 10.1111/tri.13506 and data derived from International Figures on Organ Donation and Transplantation. Newsletter Transplant. Available at https://www.edqm.eu/en/reports-and-publications. Accessed December 2019.
FIGURE 2.
FIGURE 2.:
Number of uncontrolled donors after circulatory death and transplant-related procedures during 2008–2018 in European countries. The number of European countries with at least 1 uncontrolled donation after circulatory death (DCD) procedure is indicated for each y. Source: Unpublished work from Lomero M, Lomero M, Gardiner D, Coll E, et al. Donation after circulatory death today: an updated overview of the European landscape. Transpl Int 2019 Sep 3. doi: 10.1111/tri.13506 and data derived from International Figures on Organ Donation and Transplantation. Newsletter Transplant. Available at https://www.edqm.eu/en/reports-and-publications. Accessed December 2019.

The reduced number of active programs—and the declining activity in existing ones—can be explained by the apparent complexity of the uDCD procedure, its reduced effectiveness in terms of organs deemed suitable for transplantation, the limited knowledge about the quality of uDCD organs, the resources required, and the ethical dilemmas that the procedure poses,8 issues that are subject to review in this article (Table 1).

TABLE 1.
TABLE 1.:
Areas of research, development, and implementation in uDCD

THE PROCEDURE OF uDCD

Figure 3 represents the uDCD process, as carried out in the most successful European IIa programs. After a witnessed CA, out-of-hospital EMS apply aCPR according to national protocols that are aligned with international standards,16,17 aiming for ROSC. The first duty of the EMS is to resuscitate the patient, whenever possible. The patient is only considered a potential uDCD donor when aCPR has been exhausted and considered unsuccessful by the treating team, and a set of strict inclusion criteria are met. The EMS contacts the donor coordinator at a receiving hospital for a joint evaluation based on initial on-site inclusion criteria (Table 2). After determining the donor suitability, the uDCD protocol is activated. Cardiac compression and mechanical ventilation are then extended beyond futility to preserve organs during the transfer of the potential donor to the hospital and thus retain the option of organ donation until their wishes are known. In some countries, the uDCD protocol is only activated once the irreversibility of the CA has been determined in the in-hospital setting following the transfer of patients to the hospital with a therapeutic purpose.

TABLE 2.
TABLE 2.:
Inclusion criteria for uncontrolled donation after circulatory death
FIGURE 3.
FIGURE 3.:
The process of uncontrolled donation after circulatory death (uDCD). aCPR, advanced cardiopulmonary resuscitation; CA, cardiac arrest; HRP, hypothermic regional perfusion; NRP, normothermic regional perfusion.

In existing programs, death is always certified in the hospital by physicians who are independent from the EMS and from the donor coordination and transplant teams. These professionals must ensure the irreversibility of the CA and observe a period of complete absence of spontaneous circulation and respiration. In most programs, this no-touch period is of 5 minutes.8 After death has been determined, cardiac compression and mechanical ventilation are restored for organ preservation purposes in some countries,18 where this is permitted, since death follows exhausted aCPR efforts and prolonged no-flow and low-flow periods.18,19 In the Spanish program, cardiac compression and ventilation are continued until legal permission for in situ organ preservation is obtained, which is required in most cases.

Following the determination of death and the legal authorization (when appropriate), a central vascular catheter is inserted to collect blood samples for medical purposes and for the legal authorities. Heparin is administered to the potential donor, and in situ preservation methods are then initiated. In situ preservation strategies may consist of the cooling of organs with the triple-lumen double-balloon catheter technique or the use of hypothermic regional perfusion (HRP) or normothermic regional perfusion (NRP). In HRP/NRP, an extracorporeal membrane oxygenation (ECMO) device is established to reperfuse organs with oxygenated blood. The cannulation procedures have been described previously.20,21 To restrict preservation to the abdominal cavity, an aortic occlusion balloon catheter is introduced through an arterial cannula. The proper positioning of the balloon is confirmed by a chest radiograph. Pump flow is maintained at 1.7–2.4 L/min, temperature at 36°C (NRP) or 4°C (HRP). Normothermia is always used if liver donation is considered. The maximum duration of HRP/NRP has been empirically established at 240 minutes. This time is critical to complete consent and authorization requirements and the characterization of the donor and the organs for transplantation. NRP not only facilitates the logistics of the process, but it also has the potential to regenerate ischemically damaged tissue and allows a better evaluation of the viability of organs based on the behavior of biochemical markers (aspartate aminotransferase, alanine aminotransferase, and lactate).

If lungs are preserved, a 24F tube is inserted into each hemithorax (anterior second intercostal space) and a preservation solution is instilled at 4°C for topical cooling. The orotracheal tube is left open to the exterior. Two additional tubes may be placed to allow the recirculation of the perfusion solution through a heat exchanger. Esophageal temperature is maintained below 21°C.19,22,23

Donor coordinators must assess the position of the patient towards organ donation through the donor or the advanced directives registries and a dedicated interview with their family. Discussion about donation opportunities may take place at different moments throughout the process, from the moment when aCPR is terminated, to after the initiation of in situ preservation measures. In Spain, different scenarios are considered to decide the time for this conversation, a decision that is driven by the emotional situation of relatives and their request for information.24 Once consent has been obtained and legal permission granted, organ recovery is performed.

Organs are validated in a similar way to donation after brain death (DBD) donor organs, based on function, macroscopic appearance, and histology, when appropriate. Biochemical parameters monitored during NRP are of particular interest for the validation of the liver. It has been established that livers should not be considered suitable for transplantation if alanine aminotransferase/aspartate aminotransferase levels are 4× beyond the upper normal limit at the beginning and 5× beyond the upper normal limit at the end of NRP.24 To assess the viability of lungs, after lungs have been perfused, 300 mL of donor blood are infused through the pulmonary artery and samples are taken from the effluent through the left atria to perform gasometries corrected by temperature. A Pao2/Fio2 ratio equal to or above 400 is considered appropriate. Centers, where machine perfusion (MP) is routinely applied for ex situ preservation of organs, may use specific parameters to anticipate organ viability. However, the precise role of these parameters in uDCD is still to be elucidated.

RESULTS OF uDCD

Effectiveness of the Process

uDCD can substantially contribute to increasing organ availability,21,25,26 but the effectiveness of the process is lower compared with cDCD and DBD in terms of donor utilization and the number of organs recovered and transplanted per donor.8,27 In a recent European study assessing the effectiveness of the different deceased donation pathways in 2016, utilization of uDCD donors was 75%, compared with 91% in cDCD and 93% in DBD.8 The number of organs transplanted per donor was 1.6 versus 2.6 and 3.5, respectively. This reduced effectiveness of uDCD mostly derived from a less frequent consideration of liver and lung donation, and a 32% discard rate of kidneys following recovery. The limited effectiveness of uDCD is associated with potentially modifiable and nonmodifiable factors.

Because of the urgency of the uDCD procedure, not all organs may be able to be recovered if the donor hospital lacks a specific transplant program or a well-trained and readily available recovery team. The use of in situ preservation strategies can provide time for dedicated recovery teams from other centers to reach the donor hospital in time. Therefore, it is essential that procedures are agreed upon either with local transplant teams or with reference centers that describe organ-specific selection criteria and the way organ recovery will be taking place upon the activation of uDCD.

NRP, critical if liver transplantation is considered, can preclude cold in situ preservation of lungs before recovery. This has made teams either consider liver or lung donation, and hence NRP or HRP, when activating uDCD.23 A case-by-case assessment must be made to consider either lung or liver donation, depending on organ suitability, size of the waiting list, and availability of the corresponding recovery or transplant teams. A preliminary experience with a bithermia approach to simultaneously preserve lungs in cold while using NRP has been published, but further information on this strategy is required.28

Once recovered, the high discard rates of abdominal organs mainly result from poor perfusion.27 Although poor perfusion of organs is a consequence inherent to prolonged warm ischemia in uDCD, it can be minimized through a strict control and registration of the relevant times, appropriate selection of donors and organs, and adequate preservation strategies both outside and within the hospital. This requires perfect coordination with the EMS, a continuous review of existing protocols, and training of participating staff.

Outcomes of Kidney Transplantation

uDCD has shown to significantly impact kidney transplant rates and reduce time on the waiting list.20,29-35Table 3 summarizes the most relevant experiences published in kidney transplantation from uDCD donors. Graft survival rates are acceptable in most studies. Compared to kidney transplants from standard criteria DBD donors, uDCD donor kidneys have been described as leading to similar30 or worse29 results in terms of survival and graft function. However, such results have been better29,36 or at least comparable31,38 to those obtained with kidney transplants from expanded criteria DBD donors.

TABLE 3.
TABLE 3.:
Results of kidney transplantation from uDCD donors in published series

The most important challenge in uDCD kidney transplantation is primary nonfunction (PNF), with a reported incidence ranging from 1.8%39 to 20%34,35 in the largest series. These discrepancies are partly due to differences in donor and recipient selection criteria and to variations in preservation techniques. Very strict organ selection criteria may reduce PNF, but this carries the risk of discarding viable organs.40 When excluding cases with PNF, graft survival of uDCD kidneys is similar to that of standard criteria DBD donor kidneys.29,36 Thus, uDCD kidney transplants have the potential for excellent results if further efforts are made to address the high rate of PNF. A very careful management of the donor and the recipient is critical. Several risk factors for kidney graft failure in uDCD have been identified, the most relevant series agreeing that older donor age,20,29,30,32-35 specific causes of donor death,29,32 long warm ischemia time,29,30,32,34,35 and in situ cooling of organs (versus HRP/NRP)20,37 are associated with early graft loss. Indeed, the poor results obtained with the in situ cooling of kidneys invites the abandonment of this technique. Other factors described as associated with graft loss, such as long cold ischemia time34,35 and the type of immunosuppressive therapy used,35 have not been corroborated in the largest series available.20,29,30 It should not be forgotten that uDCD organs are exposed to an unavoidable period of warm ischemia after the circulatory arrest, which may have serious implications for graft function. The use of MP for ex situ preservation, which has been effective in reducing the incidence of delayed graft function (DGF), has not been associated with a decreased risk of PNF.41-43 However, MP could become a tool to select uDCD kidneys based on the renal resistance index.44 The findings of several randomized trials are expected to be reported within the next 2 years, which may shed light on the value of different ex situ perfusion methods and indicate those perfusion parameters that may be useful to predict organ viability.

The rate of DGF is also higher in uDCD compared with DBD kidney transplantation, though for unclear reasons, DGF has no apparent effect on graft survival in most studies.29,30,36 Kidneys from uDCD donors are not exposed to the process of brain death, which may be extremely injurious and is associated with the activation of specific pathways of the innate immune system and with changes in metabolic gene expression in renal tissue.45 The use of NRP has proven to reduce DGF in different studies,31,46 but not in others.47

Regarding renal function of kidney transplants from uDCD versus standard criteria DBD donors, some studies report similar30 while others report worse29,36 values. Viglietti et al48 described an early increased posttransplant fibrosis in uDCD kidneys compared with those from DBD donors, which was associated with donor age and the duration of the no-flow period. However, the most important series published show superior estimated glomerular filtration rates (eGFR) at 5 and 10 years in recipients of uDCD versus extended criteria DBD donors.29 The duration of the donor CA has recently been reported to have an impact on renal function.48 A no-flow period of 10 minutes or shorter leads to a 1-year eGFR and an interstitial fibrosis and tubular atrophy score comparable to those described in recipients of DBD donor grafts. In contrast, when the no-flow period is longer than 10 minutes, both parameters are significantly worse. This cutoff time of 10 minutes explains the lower 1-year eGFR in the uDCD group. It has also been described that the measured GFR in recipients of uDCD kidneys is higher with NRP than with the in situ cooling of organs.47

Outcomes of Liver Transplantation

Early reports of uDCD liver transplantation included organ recovery methods different from NRP. In 1995, Casavilla et al49 from the University of Pittsburgh reported the transplantation of livers from donors who had experienced an unexpected CA after or during the process of declaring brain death. Following arrest, aCPR was maintained while donors were taken to the operating room, where super-rapid cold perfusion and recovery were performed. Six out of a total of 10 uDCD livers recovered in this fashion over a 4-year period were transplanted, but only 1 patient survived beyond 2 months. In La Coruña (Spain), livers have been transplanted from category II uDCD donors maintained with ongoing cardiopulmonary resuscitation (CPR) or NRP/HRP. Reports on this group’s experience transplanting a total of 27 livers (10 from donors maintained with simultaneous chest and abdominal compressions, 10 with NRP, and 7 with HRP) have described an 18% incidence of PNF, 42% posttransplant biliary complications, including 25% nonanastomotic biliary strictures/ischemic-type biliary lesions (ITBL), and 1-year graft survival of approximately 65%.50,51

In contrast with earlier experiences, contemporary reports on uDCD liver transplantation have all included the use of postmortem NRP. Series from Spain, France, and Italy have been published in recent years and described incidences of 8%–23% PNF, 8%–16% ITBL, and 1-year graft survival (not censored for patient death) of 69%–74% following transplantation of these grafts (Table 4). These results are inferior to those achieved with standard DBD and even with well-selected cDCD livers, though it has been noted that posttransplant results have improved from the initial to the more recent period of each group’s experiences, with 1-year graft survival rates surpassing 80% in the latter periods.52,56 Aside from meticulous donor and recipient selection criteria (recipients <60 y and low model for end-stage liver disease scores/compensated liver disease), optimized perioperative management of uDCD liver recipients, with an aggressive correction of hemodynamic and coagulation abnormalities and the prophylactic administration of tranexamic acid before graft reperfusion in all cases,57 have played an important role in the improvements in outcomes that have been observed over time.

TABLE 4.
TABLE 4.:
Donor and preservation conditions, acceptance criteria, and clinical outcomes of contemporary series of uncontrolled DCD liver transplantation

In addition to in situ NRP, ex situ MP is a technique currently under investigation to increase the number and improve the quality of DCD livers in general, and uDCD livers in particular. MP provides a continuous supply of oxygen and other substrates during the ex situ preservation period, clears metabolic wastes, and offers an opportunity to assess graft function before transplantation.54,58,59 To date, clinical experience with 15 uDCD livers undergoing in situ NRP followed by ex situ MP (14 hypothermic oxygenated MP—HOPE—and 1 normothermic MP) has been reported.54,60 While preliminary results of the aforementioned case studies have been promising, other recent reports on viability testing of marginal livers have described relatively high rates of posttransplant ITBL among cDCD recipients (25%–30%),59,61 indicating the need for further refinement of the MP technique and the selection criteria for marginal DCD grafts.

Outcomes of Lung Transplantation

The first uDCD lung transplant was published by Steen et al62 in 2001. The 54-year-old donor suffered a CA and was unsuccessfully resuscitated after 50 minutes of aCPR. After 65 minutes, the lungs were subject to intrapleural topical cooling for 3 hours before retrieval. The team evaluated the lungs with ex situ MP and then performed a single lung transplant, which also became the first lung graft following this type of ex situ assessment.

The University Hospital Puerta de Hierro (Madrid, Spain) has published the largest experience with uDCD lung transplants.22,63,64 Survival at 3 months, 1 year, and 5 years after transplantation was 78%, 68%, and 51%, respectively, and the incidence of obliterans bronchiolitis was 11%, 35%, and 45% at 1, 3, and 5 years. More recently, this same group compared the outcomes of 38 recipients of lungs from uDCD donors with those of 292 recipients of DBD lungs performed during 2002–2012.65 The early results were comparable between the 2 groups, in terms of duration of admission in the intensive care unit (10.5 versus 9 d), hospital admission (35 versus 33.5 d), and incidence of grade 3 primary graft dysfunction (34.2% versus 24%). Survival free of chronic rejection was also similar between the groups. However, significant differences were found in global survival at 1, 5, and 10 years (71.1%, 50.8%, and 16.5% versus 75%, 58.4%, and 38.1%; P = 0.048). Despite these differences, the results obtained with uDCD lungs were acceptable. Of note, 3 of the 8 uDCD lungs subject to ex situ MP-developed grade 3 primary graft dysfunction, which suggests that this type of additional assessment may not be able to identify the injury caused by warm ischemia in all cases.

In 2012, the University Hospital 12 de Octubre (Madrid, Spain) published their initial experience with 3 uDCD lung transplants with excellent short-term results.28 The University Hospital Marqués de Valdecilla (Santander, Spain) reported the results of 5 single lung uDCD transplants; with a mean ischemia time of 84 minutes, 1-month and 1-year survival was 100% and 80%, respectively.21 In the expanded series of 8 lung transplants undertaken during 2012–2018, this same group described an excellent 5-year survival of 87.5%.23 The mean ischemia time was 96.8 minutes and only the last organ was subject to ex situ MP.

In recent years, additional cases have been published by Suzuki et al66 and Valenza et al,67 all performed with ex situ MP before transplantation. In 2019, the Toronto group reported its initial experience with a uDCD program only devoted to lung recovery. Of note, intrapleural topical cooling was not undertaken before lung retrieval.68 Three uDCD lung transplants were performed over the course of 1.5 years, with a mean warm ischemia time of 160 minutes and all subject to ex situ MP. Only 1 patient, under an ECMO device as a bridge to transplantation, died as a result of a multiorgan failure 100 days after the transplant.

In summary, results of uDCD lungs are acceptable in general terms and comparable to those obtained from conventional donors. Since a prolonged warm ischemia time can compromise graft survival, it seems critical to simplify protocols and implement measures to reduce its duration, as well as to effectively preserve the lungs before recovery. The procedure of topical lung cooling is simple, cheap, and associated with appropriate outcomes. The value of ex situ MP as a tool to evaluate the viability of uDCD lungs and to repair ischemically damaged tissue is still to be validated.

ETHICAL ASPECTS

uDCD poses a set of ethical challenges that need to be overcome through a properly designed protocol.69 First, EMS may be considered to face a conflict of interests when deciding upon the termination of aCPR and activating uDCD. To avoid such potential conflict, professionals need to work in complete alignment with national and international guidance on aCPR.16,17 The cessation of aCPR must be independent of any consideration of organ donation. It is also important that healthcare professionals, independent from the EMS and the donor and transplant teams, reassess the irreversibility of the CA and determine death.70 This is one of the reasons why death is determined in the hospital in most programs. As an alternative, the New York City protocol has foreseen the participation of a dedicated organ preservation unit to start uDCD onsite once the EMS has previously and independently made the decision to terminate aCPR.71

The extension of cardiac compression and mechanical ventilation beyond futility during the transfer of the potential donor to the hospital has been questioned by some scholars.72 The alternative would be to determine death in the street and assess the wishes of the patient in the out-of-hospital setting. However, this does not seem to be the optimal approach. Extending CPR beyond futility allows the determination of death to be deferred to the hospital and the position of the patient and that of their legal representatives towards posthumous donation to be properly assessed. Determining death in the hospital provides the opportunity for an independent assessment of the irreversibility of the CA, as stressed above.70 Although rare, ROSC can potentially occur during donor transfer.73 Should this happen, it will be identified by the continuous monitoring of the patient and lead to the initiation of post-CPR treatment. Time is also required to consult the donor’s registry and the advanced directives registry. In addition, an adequate communication with family members requires time for them to understand the loss of their loved one,74 and that such a conversation is led by the most appropriate professional. Deferring the conversation with family members about donation opportunities to the hospital allows such an interview to take place in a more adequate setting, and under the leadership of experienced and properly trained professionals who will be able to devote time to relatives. This should not, however, contravene the principle of transparency in the communication process (see below).

In the most successful uDCD programs, cardiac compression and mechanical ventilation are resumed following the determination of death. In the cDCD setting, death by circulatory criteria is defined by the permanent (will not return), not by the irreversible (cannot return), cessation of circulation, that will lead to the irreversible loss of brain functions.75 After 5 minutes of the circulatory arrest that follows the withdrawal of life-sustaining therapies, cases of autoresuscitation have not been described.73 Death can be determined in this setting as long as circulation is not artificially restored to the brain. If NRP is initiated after the determination of death in cDCD, the aorta must be blocked with a balloon or by surgical clamping or vessel ligation to avoid reperfusion of the brain.5 The question is if these same criteria are applicable to the uDCD setting. As the protocols have been designed, potential uDCD donors are exposed to at least 2 no-flow periods (that of the CA and that of the no-touch period) and to prolonged periods of low-flow.18 In the Spanish experience, the median time between the CA and the determination of death is 90 minutes. This intense and prolonged ischemic injury to the brain has led to the assumption that brain death has developed at the moment CPR for preservation purposes is resumed. Still, more evidence is needed to understand the process by which no-flow and low-flow periods lead to the irreversible cessation of neurological functions.

Regarding communication with family members, transparency is a fundamental principle. However, information needs to be provided in a compassionate manner and respecting the appropriate timing.74 Decoupling information is an essential element in the family approach to discuss organ donation in any donation pathway; this means that donation is not presented as an option until the relatives have accepted and understood the death of their loved one or the poor prognosis that has led to the decision to stop therapy. Information about organ donation also needs to be provided in an appropriate setting. These concepts regarding the family approach are equally important in uDCD. Time should be provided for family members to accept their loss and they should set the pace for the provision of information. On the other hand, the EMS may feel conflicted when they transfer a patient to the hospital with the purpose of organ donation if they do not openly disclose this information to the donor’s family. To resolve this situation, the Spanish program has devised 4 different scenarios that, based on the information requested by the families and their emotional status, lead to the provision of information about prognosis and organ donation either by the EMS in the out-of-hospital setting, or by the donor coordinator once in the hospital.24,76 This second option also allows a more appropriate setting for the interview with the donor family.

Finally, extracorporeal-assisted cardiopulmonary resuscitation (E-CPR) is being developed as an option for selected patients with a refractory CA.77 Although international guidance does not support the systematic introduction of this novel approach, centers may choose to engage in clinical trials and contribute to generating evidence to support E-CPR.78 It has been suggested that an E-CPR program can conflict with uDCD and vice versa.72,79 On the contrary, a recent Portuguese experience has made evident that both programs can successfully coexist.80 Should an E-CPR program be in place and patients fulfill the selection criteria, the corresponding process should be activated, and uDCD not considered, since aCPR strategies would have not been exhausted in those particular cases. Of note, an inclusion criterion to activate an E-CPR protocol is a defibrillating rhythm, the presence of which is a contraindication to initiate uDCD since aCPR in this setting must be maintained. Other selection criteria for E-CPR include a very short no-flow period (<2–5 min) and the initiation of veno-arterial ECMO within 60 minutes of the CA.77 Therefore, there are clear differences in selection criteria between both pathways.

LOGISTICAL ASPECTS

The development of a successful uDCD program requires a well-designed logistical plan to allow for the efficient activation of the uDCD pathway once the donation opportunity has been identified. The key is to fulfill the logistical and legal requirements to reduce warm ischemic injury to the organs that will be subject to transplantation.

The presence of physicians at the scene of the CA improves the quality of assistance and makes the decision about futility of aCPR easier.69,76 The role of physicians on site that also includes the first approach to the patient’s relatives, coupled with the expertise of donor coordinators, could explain the low rates of refusals to donate described in uDCD programs.81 Indeed, Spain and France, with physician-led EMS, have developed the most successful uDCD programs.19

Although there are differences between programs, the activation of the uDCD protocol is decided based on the exchange of information between the EMS and the donor coordinator at the hospital. Therefore, it is mandatory to define clear inclusion criteria (Table 2) to facilitate the decision-making process.

The implementation of uDCD does not entail the need for additional resources on the EMS side, since these are the same as those required for aCPR. However, the use of mechanical compression devices is highly recommended to maintain an optimal chest compression during a prolonged period of time (usually >1 h) and with continuous movements in the ambulance during the transfer of the potential donor.82

Although in uDCD, several professionals are activated, only a few need to be present when the potential uDCD donor arrives at the hospital: (1) a physician on duty to diagnose death; (2) a surgeon to cannulate the femoral vessels; (3) a professional to manage the ECMO device (when HRP/NRP is used); and (4) a donor coordinator to lead and coordinate the whole process. Once the in situ preservation of organs has been initiated, other professionals involved in the retrieval and the transplantation procedures will be activated.21

The determination of death and the cannulation of vessels for organ preservation purposes can be performed in the emergency department, the intensive care unit, or the operating room. As warm ischemia time needs to be reduced as much as possible, it is desirable that the entire procedure takes place in the same unit.21

In most cases, legal permission will be required for cannulation of femoral vessels and organ retrieval. Therefore, a clear protocol including judges and coroners is highly recommended.19,21

In order to minimize the duration of cold ischemia, it is advisable that organs are allocated locally and only shared with other centers in the event that no suitable recipients are identified on the local waiting lists.20 In such cases, fast-track allocation schemes should be used to make the organ offers to centers that have previously expressed interest in using uDCD organs for transplantation.

CONCLUSIONS

uDCD is a complex procedure from a logistical point of view and can only be developed under an appropriate regulatory framework that deals with the ethical challenges that it poses. uDCD can significantly contribute to increase transplantation activities and leads to acceptable posttransplant outcomes, that can improve if modifiable and well-identified factors are controlled. Making uDCD possible after an unsuccessfully resuscitated CA not only improves patient access to transplantation therapies, but it also provides more patients with the unique opportunity to donate organs upon their death, if donation is consistent with their wishes and values.

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