Uncontrolled Donation After Cardiac Death Research Articles

Donation After Cardiac Death, a Possibility to Expand the Donor Pool: Review and the Hungarian Experience

IntroductionLung transplantation is the only successful treatment option for patients experiencing end-stage lung disease. Results have improved significantly in the last decade; however, the number one limiting factor is still the shortage of donor lungs. Due to the discrepancy between available donor lungs and patients awaiting lung transplantation, many centers have reintroduced donation after cardiac death (DCD). According to their results, DCD and donation after brain death (DBD) are comparable in terms of survival and graft function.Currently in Hungary, donation is only allowed from DBD donors; however, due to the Eurotransplant agreement, non-heart-beating donation (NHBD) organs can be transplanted into Hungarian patients, and in some cases Hungarian transplant teams can also take part in NHBDs within the Eurotransplant region.The Hungarian experience. A Hungarian patient received a lung from a 15-year-old uncontrolled DCD in Vienna. The donor was reanimated for 54 minutes and after lung procurement the lungs were put on ex vivo lung perfusion and later successfully implanted into the Hungarian recipient. The recovery was very successful and the patient is still alive.The Hungarian Lung Transplantation Team was involved in a controlled Maastricht III donation in 2017. A 49-year-old female donor was reported from Ghent, Belgium. A multiorgan donation was carried out with 15 minutes of warm ischemic time in the case of the lungs. ConclusionDCD is an effective, safe, and available method to increase the donor pool. In the case of controlled donations, the necessary protocols have already been prepared. Although DBD is working very successfully in Hungary, infrastructural developments, education of professionals, and social preparations are all needed to implement a DCD protocol in Hungary.

Successful donation after cardiac death liver transplants with prolonged warm ischemia time using normothermic regional perfusion.

The role of donation after cardiac death (DCD) in expanding the donor pool is mainly limited by the incidence of primary nonfunction (PNF) and ischemia-related complications. Even greater concern exists toward uncontrolled DCD, which represents the largest potential pool of DCD donors. We recently started the first Italian series of DCD liver transplantation, using normothermic regional perfusion (NRP) in 6 uncontrolled donors and in 1 controlled case to deal with the legally required no-touch period of 20 minutes. We examined our first 7 cases for the incidence of PNF, early graft dysfunction, and biliary complications. Acceptance of the graft was based on the trend of serum transaminase and lactate during NRP, the macroscopic appearance, and the liver biopsy. Hypothermic machine perfusion (HMP) was associated in selected cases to improve cold storage. Most notably, no cases of PNF were observed. Median posttransplant transaminase peak was 1014 IU/L (range, 393-3268 IU/L). Patient and graft survival were both 100% after a mean follow-up of 6.1 months (range, 3-9 months). No cases of ischemic cholangiopathy occurred during the follow-up. Only 1 anastomotic stricture completely resolved with endoscopic stenting. In conclusion, DCD liver transplantation is feasible in Italy despite the protracted no-touch period. The use of NRP and HMP seems to earn good graft function and proves safe in these organs. Liver Transplantation 23 166-173 2017 AASLD.

Between a Rock and a Hard Place: Terminating Cardiopulmonary Resuscitation and Preserving Opportunities for Organ Donation.

Editorials6 December 2016Between a Rock and a Hard Place: Terminating Cardiopulmonary Resuscitation and Preserving Opportunities for Organ DonationJoanna L. Hart, MD, MS and Scott D. Halpern, MD, PhDJoanna L. Hart, MD, MSFrom Perelman School of Medicine and Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania.Search for more papers by this author and Scott D. Halpern, MD, PhDFrom Perelman School of Medicine and Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M16-2056 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Of the more than 300 000 out-of-hospital cardiac arrests (OHCAs) that occur annually in the United States, approximately 90% result in death (1). Prolonged resuscitation attempts may harm patients, family members, and those performing or witnessing the resuscitation. These adverse consequences may arise after resuscitative efforts in the field or en route to or in the emergency department. However, termination of resuscitation outside the hospital forecloses opportunities for organ donation. Advances in uncontrolled donation after cardiac death (UDCD) make successful organ recovery feasible if resuscitation is continued. Hence, society has interests not only in terminating resuscitative efforts that will not restore ...

Donor gluconate rescues livers from uncontrolled donation after cardiac death

Ischemia from organ preservation or donation causes cells and tissues to swell owing to loss of energy-dependent mechanisms of control of cell volume. These volume changes cause substantial preservation injury, because preventing these changes by adding cell impermeants to preservation solutions decreases preservation injury. The objective of this study was to assess if this effect could be realized early in uncontrolled donation after cardiac death (DCD) livers by systemically loading donors with gluconate immediately after death to prevent accelerated swelling injury during the warm ischemia period before liver retrieval. Uncontrolled DCD rat livers were cold-stored in University of Wisconsin solution for 24 hours and reperfused on an isolated perfused liver (IPL) device for 2 hours or transplanted into a rat as an allograft for 7 days. Donors were pretreated with a solution of the impermeant gluconate or a saline control immediately after cardiac death. Livers were retrieved after 30 minutes. In vivo, gluconate infusion in donors immediately before or after cardiac death prevented DCD-induced increases in total tissue water, decreased vascular resistance, increased oxygen consumption and synthesis of adenosine triphosphate, increased bile production, decreased lactate dehydrogenase release, and decreased histology injury scores after reperfusion on the IPL relative to saline-treated DCD controls. In the transplant model, donor gluconate pretreatment significantly decreased both alanine aminotransferase the first day after transplantation and total bilirubin the seventh day after transplantation. Cell and tissue swelling plays a key role in preservation injury of uncontrolled DCD livers, which can be mitigated by early administration of gluconate solutions to the donor immediately after death.

228 Therapeutic Effect of Surfactant Inhalation on Lungs Donated after Cardiac Death in a Canine Lung Transplantation Model

In lung transplantation, donation after cardiac death (DCD) has been introduced worldwide. To date, several programs have reported acceptable outcomes; however, the number of patients on waiting lists is indeed much more than that of the donated organs. Therefore, we considered the effective use of marginal donor grafts from uncontrolled DCD donors by investigating the effect of surfactant inhalation against pulmonary ischemia-reperfusion injury in canine lungs from DCD donors.

Kidney donation after cardiac death

There is continuing disparity between demand for and supply of kidneys for transplantation. This review describes the current state of kidney donation after cardiac death (DCD) and provides recommendations for a way forward. The conversion rate for potential DCD donors varies from 40%-80%. Compared to controlled DCD, uncontrolled DCD is more labour intensive, has a lower conversion rate and a higher discard rate. The super-rapid laparotomy technique involving direct aortic cannulation is preferred over in situ perfusion in controlled DCD donation and is associated with lower kidney discard rates, shorter warm ischaemia times and higher graft survival rates. DCD kidneys showed a 5.73-fold increase in the incidence of delayed graft function (DGF) and a higher primary non function rate compared to donation after brain death kidneys, but the long term graft function is equivalent between the two. The cold ischaemia time is a controllable factor that significantly influences the outcome of allografts, for example, limiting it to < 12 h markedly reduces DGF. DCD kidneys from donors < 50 function like standard criteria kidneys and should be viewed as such. As the majority of DCD kidneys are from controlled donation, incorporation of uncontrolled donation will expand the donor pool. Efforts to maximise the supply of kidneys from DCD include: implementing organ recovery from emergency department setting; improving family consent rate; utilising technological developments to optimise organs either prior to recovery from donors or during storage; improving organ allocation to ensure best utility; and improving viability testing to reduce primary non function.

Peculiar mechanisms of graft recovery through anti-inflammatory responses after rat lung transplantation from donation after cardiac death

BackgroundAlthough lung transplantation from donation after cardiac death (DCD), especially uncontrolled DCD, is limited by warm ischemic periods, the molecular mechanism of warm ischemia–reperfusion-injury (IRI) has not been well elucidated. The purpose of this study was to clarify the particular longitudinal mechanisms of molecular factors involved in warm IRI. MethodsCold ischemic-time (CIT)-group lungs were retrieved and subjected to 3-h of cold preservation, whereas warm ischemic-time (WIT)-group lungs were retrieved after 3-h of warm ischemia. Orthotopic rat lung transplantation was performed and the grafts were reperfused for 1 or 4-h. The graft functions, gene expression, and activation of inflammatory molecules in the grafts were analyzed. Exhaled-carbon-monoxide-concentration (ExCO-C) was measured during reperfusion. ResultsOnly the WIT-group showed obvious primary graft dysfunction at 1-h reperfusion, but the graft function was recovered during 4-h reperfusion. Most of pro-inflammatory cytokines and stress-induced molecules showed different expression and activation patterns between CIT and WIT groups. In the WIT-group, the expressions of anti-inflammatory molecules, IL-10 and HO-1, were significantly increased at 1-h reperfusion compared to the CIT-group, and these high levels were maintained through 4-h reperfusion. Furthermore, ExCO-C levels in the WIT-group increased immediately after reperfusion compared to the CIT-group. ConclusionsThis study indicates that warm IRI may involve a different mechanism than cold IRI and anti-inflammatory pathways may play important roles in the graft recovery after lung transplantation from uncontrolled DCD.

The effect of normothermic recirculation before cold preservation on post-transplant injury of ischemically damaged donor kidneys

Kidneys recovered from donation after cardiac death (DCD) are increasingly used to enlarge the deceased donor pool. Such renal grafts, especially those derived from uncontrolled DCD, have inevitably sustained profound warm ischemic injury, which compromises post-transplant function. Normothermic recirculation (NR) of the deceased donor's body before organ cooling could be an interesting approach to mitigate the detrimental effect of warm ischemia. To date, however, there is no evidence coming from preclinical studies to support the principle of NR in kidney transplantation. In this study, we subjected 48 Lewis rat kidneys to 15 or 30 min of warm ischemia, and subsequently 0, 1, or 2 h of NR. After 24 h cold storage, kidneys were transplanted into a recipient animal and 24 h later we measured the percentage of cortical necrosis, and determined gene expression of heme oxigenase-1, heat shock protein-70, transforming growth factor-β, kidney injury molecule-1, interleukin-6, hypoxia inducible factor-1α, monocyte chemoattractant protein-1, and α-smooth muscle actin in kidney tissue. We found that NR had no significant influence on any of these markers. Therefore, we conclude that this animal study by no means supports the presumed beneficial effect of NR on kidneys that have been severely damaged by warm ischemia.

Effect of Preprocurement Ventilation on Lungs Donated After Cardiac Death in a Canine Lung Transplantation Model

One method of countering chronic lung donor shortages is the practice of donation after cardiac death (DCD). However, this technique inevitably leads to pulmonary dysfunction related to warm ischemia. One promising method of alleviating this problem is ventilation. However, it can rarely be initiated from the onset of cardiac arrest, particularly in uncontrolled DCD donors. We investigated the protective effect of the last 60 min of ventilation during a 240-min warm ischemic time. We rendered donor dogs cardiac dead and left them at room temperature. Six dogs received ventilation with 100% oxygen for 60 min starting at 180 min after cardiac arrest (ventilation group). Eight dogs received no ventilation. Lungs were harvested 240 min after cardiac arrest, then transplanted into recipient dogs. At 60 min after reperfusion, the right pulmonary artery was ligated, and the function of the left transplanted lung was evaluated. In the ventilation group, all six animals survived for 240 min after reperfusion, whereas in the nonventilation group, only four of eight survived. The ventilation group demonstrated significantly better pulmonary oxygenation, shunt fraction, and wet-to-dry weight ratio. Furthermore, the ventilation group revealed significantly higher levels of high-energy phosphates in the lung tissues, fewer apoptotic cells, lower levels of tumor necrosis factor-α and interleukin-8 messenger RNA in the lung tissues, and lower levels of interleukin-6 messenger RNA in the serum. Our results suggest that ventilation during the late phase of the preprocurement period may ameliorate ischemia-reperfusion injury in DCD donors.

Uncontrolled organ donation following prehospital cardiac arrest: a potential solution to the shortage of organ donors in the United Kingdom?

Uncontrolled donation after cardiac death (DCD) could increase the donor pool in the UK. Air ambulance (AA) teams may be well placed to recruit these donors. They cover large geographical areas, have short transfer times and tasked predominantly to life-threatening cases. The potential to recruit from this pool of donors was reviewed. Seventy-five month activity of an AA unit was analysed identifying patients who entered prehospital cardiac arrest (PHCA). Patients over 70 years of age were excluded as were those whose cardiac arrest was unwitnessed. A minimum potential donor pool was estimated based upon patients dying of medical causes. Rates of bystander resuscitation, mechanism of death and patient demographic data were observed. During 10,022 missions 534 patients entered PHCA. A total of 106 patients met inclusion criteria. There were 12 paediatric cases; 39 cases of 17-50 year olds and 55 cases of 50-70 year olds. Medical and traumatic causes of death accounted for 60 and 46 cases respectively. Bystander resuscitation efforts were provided in 47% of cases. A regional AA could contribute to a national uncontrolled DCD programme. Given that there are 31 AA's in England and Wales, we estimate that there could be a minimum of 300 additional potential donors annually.

Part 3: Evidence Evaluation Process

Part 3: Evidence Evaluation Process

Donation after cardiac death: evaluation of revisiting an important donor source

To date, with a widening gap between organ supply and demand, many centres are revisiting donation after cardiac death (DCD) in order to enlarge the deceased donor pool. With increasing numbers of grafts that have suffered from prolonged warm ischaemia (WI), maintenance of organ viability has once again become an important factor to preserve current high standards for functional outcome and long-term survival after transplantation. The amount of injury differs for the various DCD donor categories (Table 1) [1]. Category III donors are most widely used, since the duration of WI is known and usually short. In addition, organ recovery can be planned in advance. Nevertheless, the time interval between withdrawal of treatment and cardiac arrest in the potential donor may account for additional WI injury due to low oxygenation and organ hypoperfusion. This period is usually not included in calculations of total WI time, but it is likely to be relevant to appreciate the real ischaemic insult that a particular organ has sustained. The length of this so-called agonal phase varies widely between individual donors, and many different upper limits for acceptable donation are in use, depending on which organs are to be procured. While, for example, in The Netherlands, a maximum period of 2 h is considered acceptable for kidney donation [2], US guidelines recommend no more than 60 min [3]. Since ischaemic injury accumulates as a continuum, influenced by a multitude of factors, setting an evidence-based cut-off value for the maximum length of the agonal phase remains difficult. Suntharalingam et al. have recently conducted a comprehensive multi-centre study to identify clinical parameters that independently predict the timing of death following treatment withdrawal. Their data show that younger age, higher FiO2, and the mode of ventilation (no pressure support versus pressure support) are independently associated with a shorter agonal phase before cardiocirculatory death [4]. These are important findings, as they may allow better identification of patients suitable for DCD and facilitate timing of organ retrieval. Various guidelines are in use for the maximum acceptable duration of true WI (commonly defined as the interval between a mean arterial pressure below 60 mmHg and initiation of organ perfusion). Most up-to-date evidence shows that, for the liver, a WI time above 20–30 min and, for the kidney, a WI time longer than 45–60 min is associated with increased complications post-transplant [5]. In some countries, donation after withdrawal of treatment is illegal. As a result, transplant programmes have to rely solely on uncontrolled DCD in which the average WI time is considerably longer. However, uncontrolled DCD may have one advantage over category III donors: Serious brain injury is associated with a significant pro-inflammatory and pro-coagulatory response in the donor, which has a negative effect on organ quality and increases the risk of immunological complications post-transplant [6]. Most controlled DCD donors have sustained irreversible cerebral injury. As a result, their organs may suffer more from negative immunological and coagulatory effects than grafts derived from uncontrolled DCD donors whose primary medical condition is usually not neurologic. In renal transplantation, the detrimental effect of delayed graft function (DGF) on graft survival (GS) appears to be more pronounced in kidneys derived from brain-injured donors versus organs coming from uncontrolled DCD donors [7]. These data suggest that WI plus profound cerebral injury could account for a different, more detrimental form of DGF than observed in uncontrolled DCD kidneys that have sustained only WI.

Application of an automated cardiopulmonary resuscitation device for kidney transplantation from uncontrolled donation after cardiac death donors in the emergency department

Vital-organ transplantation has become acceptable as the treatment of choice for end-stage organ failure. If the patient, facing the end of life, wishes to donate organs after cardiac arrest (CA), donation after cardiac death (DCD) is increasingly important for the realization of the patient's desires after CA. In Japan, kidney transplantation from uncontrolled DCD donors, who are identified in modified Maastricht categories II or V, is one of the critical factors in expanding the donor pool. However, according to the forensic code for post-mortems and the requirement of legal consent for transplantation, the time required to meet all procedural requirements has sometimes prohibited organ procurement from uncontrolled DCD donors. We have therefore attempted to use an automated cardiopulmonary resuscitation (CPR) device and maintain arterial pressure for uncontrolled DCD donors during all interim procedures after sudden CA. Comparing kidneys procured from standard DCD donors (n = 10) and uncontrolled DCD donors (n = 4), significant differences were seen in warm ischemic time (WIT), defined as the time from CA to initiation of cooling in situ. However, our early experience showed good tolerance and viability of uncontrolled DCD kidneys. Immediate availability of an automated CPR device might provide a bridge to kidney procurement from uncontrolled DCD donors.

Peritoneal Cooling May Provide Improved Protection for Uncontrolled Donors After Cardiac Death: An Exploratory Porcine Study

Uncontrolled donation after cardiac death (DCD) renal transplantation relies on rapid establishment of organ preservation interventions. We have developed a model of the uncontrolled DCD, comparing current in situ perfusion (ISP) techniques with additional peritoneal cooling (PC). Ten pigs were killed and subjected to a 2 h ischemia period. The ISP group modeled current DCD protocols. The PC group (PC) modeled current protocols plus PC. Two animals were used as controls and subjected to 2 h of warm ischemia. Core renal temperature and microdialysis markers of ischemia were measured. Preservation interventions began at 30 min, with rapid laparotomy and kidney recovery performed at 2 h, prior to machine perfusion viability testing. The final mean renal temperature achieved in the ISP group was 26.3 degrees C versus 16.9 degrees C in the PC group (p = 0.0001). A significant cryopreservation benefit was suggested by lower peak microdialysate lactate and glycerol levels (ISP vs. PC, p = 0.0003 and 0.0008), and the superiority of the PC group viability criteria (p = 0.0147). This pilot study has demonstrated significant temperature, ischemia protection and viability assessment benefits with the use of supplementary PC. The data suggests a need for further research to determine the potential for reductions in the rates of ischemia-related clinical phenomena for uncontrolled DCDs.

Improved Preservation of Warm Ischemic Livers by Hypothermic Machine Perfusion with Supplemented University of Wisconsin Solution

Hypothermic machine perfusion (HMP) has the potential to improve recovery and preservation of Donation after Cardiac Death (DCD) livers, including uncontrolled DCD livers. However, current perfusion solutions lack the needed substrates to improve energy recovery and minimize hepatic injury, if warm ischemic time (WIT) is extended. This proof-of-concept study tested the hypothesis that the University of Wisconsin (UW) solution supplemented with anaplerotic substrates, calcium chloride, thromboxane A2 inhibitor, and antioxidants could improve HMP preservation and minimize reperfusion injury of warm ischemic livers. Preflushed rat livers subjected to 60 min WIT were preserved for 5 h with standard UW or supplemented UW (SUW) solution. Post preservation hepatic functions and viability were assessed during isolated perfusion with Krebs–Henseleit solution. Livers preserved with SUW showed significantly (p <. 001) improved recovery of tissue ATP levels (μ mol/g liver), 2.06 ± 0.10 (mean ± SE), as compared to the UW group, 0.70 ± 0.10, and the level was 80% of that of fresh control livers (2.60 ± 0.13). At the end of 1 h of rewarming, lactate dehydrogenase (U/L) in the perfusate was significantly (p <. 05) lower in the SUW group (429 ± 58) as compared to ischemia–reperfusion (IR) (781 ± 12) and the UW group (1151 ± 83). Bile production (μ g/min/g liver) was significantly (p <. 05) higher in the SUW group (280 ± 13) as compared to the IR (224 ± 24) and the UW group (114 ± 14). The tissue edema formation assessed by tissue wet–dry ratio was significantly (p <. 05) higher in UW group. Histology showed well-preserved hepatic structure in the SUW group. In conclusion, this study suggests that HMP with SUW solution has the potential to restore and preserve livers with extended WIT.

Using livers from donation after cardiac death donors—A proposal to protect the true Achilles heel

As the waiting list for organ transplant continues to increase (over 90,000 candidates as of May 30, 2007), the pressure to increase the number of donor organs is the impetus to expand the use of organs from donation after cardiac death (DCD) donors. The focus on DCD, previously referred to as non–heart-beating donor (NHBD), has led to significant increases in its utilization (Table 1), although the contribution to the donor pool remains only 7% in the United States and is disproportionately reflected in increased kidney transplants (Table 2). Prior to the acceptance of brain death, donors were required to have cessation of heart function in order to procure organs for transplantation. In some areas where brain death legislation has not been widely adopted, such as Asia, DCD represents a significant source of organs for transplantation. Although the Maastricht Conference on DCD in 1994 identified 4 categories of DCD [Category I: dead on arrival; Category II: unsuccessful resuscitation; Category III: waiting cardiac death; and Category IV: cardiac death in a braindead donor], it is easier to envision DCD based on two distinct populations, one following uncontrolled cardiopulmonary arrest (Categories I and II) and the other under conditions of controlled removal from life support, without the criteria for brain death being fulfilled. In 1995, the University of Pittsburgh provided one of the earliest comparisons between controlled and uncontrolled DCD. There were 24 DCD livers, 14 in the uncontrolled group (Group 1) and 10 in the group in which controlled termination of life support was performed in the operating room (Group 2). Of the liver grafts that were used, the immediate graft function rate was 50% (3/6) in Group 1 and 100% (6/6) in Group 2; however, the overall 2-year patient and graft survival was only 58% and 33%, respectively. In order to improve outcomes with DCD donors, the decision was made to avoid using uncontrolled DCD livers and, with further experience, to more carefully control risk factors [e.g., avoidance of old ( 60 year old) DCD donors, avoidance of donors with long ( 60 minutes) warm ischemic times during procurement, avoidance of confounding factors in the DCD donors, and minimization of cold ischemic times]. While patient survival and graft survival have improved in more recent eras, the impact of DCD on liver transplantation, as assessed from the Scientific Registry of Transplant Recipients (SRTR) database, shows that DCD graft survival was significantly lower than that of donation after brain death (DBD) grafts, with 1and 3-year graft survival of 70.2% and 63.3% for DCD recipients versus 80.4% and 72.1% for recipients of livers from conventional DBD donors. Recipients of a DCD graft had a greater incidence of primary nonfunction (11.8 versus 6.4%) and retransplantation (13.9% versus 8.3%) compared with DBD recipients. Similar findings have also been reported at single centers 12,13 The mandated period of warm ischemia imposed during the process of certifying death in controlled DCD leads to stagnation of blood in the microcirculation.

Expanding the Donor Kidney Pool: Utility of Renal Allografts Procured in a Setting of Uncontrolled Cardiac Death

The chronic shortage of deceased kidney donors has led to increased utilization of donation after cardiac death (DCD) kidneys, the majority of which are procured in a controlled setting. The objective of this study is to evaluate transplantation outcomes from uncontrolled DCD (uDCD) donors and evaluate their utility as a source of donor kidneys. From January 1995 to December 2004, 75,865 kidney-alone transplants from donation after brain death (DBD) donors and 2136 transplants from DCD donors were reported to the United Network for Organ Sharing. Among the DCD transplants, 1814 were from controlled and 216 from uncontrolled DCD donors. The log-rank test was used to compare survival curves. The incidence of delayed graft function in controlled DCD (cDCD) was 42% and in uDCD kidneys was 51%, compared to only 24% in kidneys from DBD donors (p < 0.001). The overall graft and patient survival of DCD donors was similar to that of DBD donor kidneys (p = 0.66; p = 0.88). Despite longer donor warm and cold ischemic times, overall graft and patient survival of uDCD donors was comparable to that of cDCD donors (p = 0.65, p = 0.99). Concerted efforts should be focused on procurement of uDCD donors, which can provide another source of quality deceased donor kidneys.