Time to death after withdrawal of treatment in donation after circulatory death (DCD) donors

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1 REVIEW C URRENT OPINION Time to death after withdrawal of treatment in donation after circulatory death (DCD) donors J.A. Bradley, G.J. Pettigrew, and C.J. Watson Purpose Controlled donation after circulatory death (DCD) donors make an important contribution to organ transplantation but there is considerable scope for further increasing the conversion of potential to actual DCD organ donors. The period between withdrawal of life-supporting treatment and death (the withdrawal period) is a major determinant of whether organ donation proceeds and it is therefore timely to review recent relevant studies in this area. Recent Findings The duration and haemodynamic nature of the withdrawal period is extremely variable, and clinical guidelines for management of the potential donor during this period differ widely. Recent evidence suggests that kidneys from DCD donors with a prolonged withdrawal period can be used to increase the number of transplants performed and provide satisfactory graft function, suggesting that it is not the duration but the haemodynamic profile of the donor during this phase that are important. This suggestion questions the relevance of clinical indices predicting death within 1 h of treatment withdrawal. Summary Future studies should aim to define clinical and physiological variables during the withdrawal period that can be used to maximize well tolerated use of organs from potential DCD donors; these thresholds are likely to differ according to organ type. Keywords circulatory death, donation after circulatory death donor, deceased donor, kidney transplantation INTRODUCTION Donation after circulatory death (DCD) donors have become a major source of organs for transplantation in the United Kingdom, The Netherlands, Australia and the USA, and several other countries are developing DCD organ transplant programmes [1 && ]. Even where well established DCD programmes exist, there is considerable scope for further expansion. Nevertheless, DCD donor schemes pose a number of important challenges in terms of identification of potential donors and managing them appropriately within an ethically and legally acceptable framework that maximizes the number of transplantable organs obtained and minimizes warm ischaemic injury [1 &&,2]. The vast majority of DCD donors are controlled Maastricht category III donors [3]. Such donors do not fulfil the criteria for certification of death by neurological testing but most have irreversible brain injuries such that the clinicians caring for them have concluded that further treatment is not in the patient s best interest. Life-supporting treatment is therefore withdrawn, following which circulatory arrest occurs and death is verified. The period from withdrawal of life-supporting treatment to circulatory arrest is highly variable and may range from a few minutes to many hours, and occasionally days. Its duration and nature has a major impact on whether organ donation is likely to occur and on the quality of the organs retrieved for transplantation. This review provides a brief update on the latest outcomes after transplantation with organs from controlled DCD donors. It then outlines the challenges posed after withdrawal of life-supporting treatment in potential DCD donors, both for intensive care and transplant clinicians. Of particular Department of Surgery, University of Cambridge, and Cambridge NIHR Biomedical Research Centre, Cambridge, United Kingdom Correspondence to Professor J. Andrew Bradley, University Department of Surgery, Addenbrooke s Hospital, Cambridge, United Kingdom. CB2 0QQ. Tel: ; jab52@cam.ac.uk Curr Opin Organ Transplant 2013, 18: DOI: /MOT.0b013e32835ed81b ß 2013 Wolters Kluwer Health Lippincott Williams & Wilkins

2 Organ preservation and procurement KEY POINTS Outcomes after controlled DCD donor kidney, pancreas and lung transplantation are similar to that for organs from DBD donors, but DCD donor livers have a higher rate of biliary complications. There is considerable scope for increasing further the conversion of potential controlled DCD organ donors to actual organ donors. There are several clinical scoring systems for predicting the likely duration of the time to asystole after withdrawal of life-supporting treatment (withdrawal period) but their clinical utility remains unclear. Time to cardiorespiratory arrest after withdrawal of lifesupporting treatment does indicate the degree of ischaemic organ injury in DCD donors. interest is the extent to which it is possible to predict the duration and nature of this time period and the implications for subsequent transplant outcome. Outcome after transplantation with organs from donation after circulatory death donors Recent analysis of outcome after transplantation with organs from DCD donors generally shows that the outcomes after kidney, pancreas and lung transplantation are broadly similar for DCD and donation after brain death (DBD) donor organs [4 9]. However, it is important to note that current practice for DCD donor selection and organ retrieval is probably conservative and does not explore the extremes of warm ischaemia. The largest experience of transplantation using organs from DCD donors relates to kidney transplantation. This is not only because they are the most common type of organ transplanted but also because, in contrast to other organ types, a period of delayed graft function resulting from ischaemic injury is not life threatening and can easily be supported by dialysis. Several recent single centre studies have shown that kidneys from DCD donors have a high rate of delayed graft function but graft survival is comparable with that for kidneys from DBD donors [4,5]. In the United Kingdom, there has been a very marked increase in kidney donation after circulatory death accounting for over one-third of kidney transplants from deceased donors. Analysis of UK transplant registry data shows that kidneys from controlled DCD donors and DBD donors have similar graft survival and function up to 5 years following transplantation [6]. A more recent analysis confirmed these findings and shows that kidneys from older DCD donors fare as well as those from older DBD donors, although DCD kidneys are more susceptible to cold ischaemic injury [10 & ]. Similarly, recent single-centre studies of pancreas transplantation have shown that grafts from DCD donors have a similar outcome [7], and UK registry data on pancreas transplantation have shown that early (1 year) graft survival is similarly good for grafts from DCD and DBD donors [11]. In the case of lung transplantation, several recent single centre reports have shown that grafts from DCD donors have similar outcomes to those reported for DBD donor organs [4,8,9,12]. In contrast with kidney, pancreas and lung transplants, liver transplantation using grafts from DCD donors is associated with a worse outcome and an increased risk of biliary complications, including ischaemic cholangiopathy [4]. A large cohort analysis derived from the United Network of Organ Sharing/Organ Procurement and Transplantation Network database revealed that, overall, recipients of liver transplants from DCD donors had significantly worse survival compared with those receiving grafts from DBD donors [13]. Children who received a DCD graft showed similar survival to those receiving a graft from a DBD donor, and for the whole DCD cohort, favorable donor characteristics included a cold ischaemic time of less than 8 h and warm ischaemic time less than 20 min [13]. Although DCD livers appear not to be as good as those from DBD donors, the outcomes following transplantation need to be balanced against the high waiting list mortality. Terminology in controlled donation after circulatory death donors Certain timepoints between withdrawal of treatment and in-situ cold perfusion of the organs are recognized (Fig. 1), although the terminology around the various timeperiods varies and there is a need for an unambiguous and universally adopted nomenclature. Withdrawal of life-supporting treatment usually involves cessation of inotropes and disconnection of ventilatory support; in many cases the potential donor is also extubated at this timepoint. The donor then enters the withdrawal or agonal period, that is the time period up until asystole. During the withdrawal period the circulation may collapse very quickly, or there may be a period of continued respiration and circulatory stability until eventually respiration becomes less frequent and effective, and the blood pressure falls. At some point, during this withdrawal period, the blood pressure is no longer sufficient to maintain organ viability and functional warm ischaemia Volume 18 Number 2 April 2013

3 Time to death in donation after circulatory death organ donors Bradley et al. Total warm ischaemic period Functional warm ischaemic period Withdrawal (agonal) period Asystolic warm ischaemic period Withdrawal of life-supporting treatment Inadequate organ perfusion Circulatory arrest Confirmation of death In-situ cold perfusion FIGURE 1. Graphic depicting the different time periods relating to donation after circulatory death (DCD) organ donation. begins. Circulatory arrest follows and true warm ischaemia begins (the asystolic warm period), and extends until the donor organs are flushed in situ with cold preservation solution or a circulation is restored using a normothermic extracorporeal oxygenation circuit. At some point following circulatory arrest death can be verified; in the United Kingdom this is 5 min, but there is no international agreement. The evidence for a specific blood pressure or oxygen saturation at which functional warm ischaemia begins is poor, and different countries and transplant organisations have chosen different values, ranging from a SBP of 35 mmhg to a mean arterial pressure of 60 mmhg [14 16]. Whether systolic, diastolic, or mean arterial pressure is the best measurement to use remains to be determined. Similarly, low oxygen saturation has been taken as a threshold for functional warm ischaemia, but the threshold varies from 25 to 70% [14,16]. However, the oxygen saturations measured on a finger probe are likely to be different from those measured using a probe on the tongue (central perfusion) or a femoral artery blood gas, since as hypotension develops there is reflex peripheral vasoconstriction. Moreover, age of the potential donor should also be taken into account as it is likely that in a previously hypertensive elderly individual, the threshold blood pressure for adequate perfusion of organs is very different from that of an otherwise fit young adult. The point at which asystole occurs is not clearly defined, and may variously be taken as the cessation of contractions on echocardiography, loss of a pulse wave on an arterial blood pressure monitor, or cessation of electrical activity. In reality, the circulation has stopped sometime before electrical activity ceases, so, in determining the precise ischaemic time, it is important to know upon what basis circulatory arrest was defined. Which option is used in practice depends on national recommendations and the discretion of the non-transplant clinician who verifies death. There is considerable variability in the way that different organisations and centres have defined the duration of warm ischaemia for organs from controlled DCD donors and this factor may have an important influence on whether organs are used for transplantation or considered unsuitable [14]. United States guidelines have defined total warm ischaemic time as the timeperiod from withdrawal of life-supporting treatment to in-situ perfusion [15] and this definition has been used by many to define usability of organs [17 19]. Although easily measured, total warm ischaemic time fails to take into account the large variability in haemodynamic parameters following withdrawal of life-supporting treatment. A more meaningful approach is to distinguish between total warm ischaemic time and functional warm ischaemic time [14,15,20 & ]. Treatment withdrawal in controlled donation after circulatory death donors To understand the impact of treatment withdrawal on the length and characteristics of the withdrawal period it is necessary to consider the clinical context of the withdrawal process in more detail. The United Kingdom has one of the largest number of DCD donors per million population in the World [1 && ] and hence a UK perspective maybe particularly informative. The UK wide prospective donor audit shows that the most common diagnoses in DCD donors are intracranial haemorrhage (45%), hypoxic brain damage (25%) and trauma/head injury (11%). There must be universal agreement that the decision to withdraw treatment is in the best interests of the patient and independent from any considerations regarding organ donation. Once the decision to withdraw treatment has been made and consent for organ donation sought, withdrawal ß 2013 Wolters Kluwer Health Lippincott Williams & Wilkins 135

4 Organ preservation and procurement of life-supporting treatment may be delayed until arrangements for organ retrieval have been finalized. The practical details of how withdrawal of lifesupporting treatment is managed vary widely between and within different countries. Clinical guidelines in this area focus predominantly on the general principles of treatment withdrawal rather than the specific details. In the UK, there is, for example, no consensus on airway management during treatment withdrawal. Data from the UK Potential Donor Audit suggest that extubation (i.e. removal of the endotracheal tube) is more often associated with progression to actual organ donation than reduction/withdrawal of ventilation without extubation (15 vs. 4%) and most actual DCD donors in the UK are extubated [1 && ]. There is no consensus in the UK on the use of additional sedation and analgesia during treatment withdrawal in potential DCD donors and controversy exists regarding the limitations of treatment that facilitates organ donation but might hasten death [21]. There is also wide variation in whether withdrawal of treatment is undertaken in the ICU or whether the potential donor is transferred to the operating theatre for treatment withdrawal so that warm ischaemic time following diagnosis of death is not extended by the need for transfer. If treatment is withdrawn in the operating theatre, there are clear guidelines aimed to ensure end-of-life care is given appropriately without involvement of the organ transplant team [22]. In the UK, intervention prior to death is not allowed, so neither administration of drugs, such as heparin nor procedures, such as femoral cannulation are permitted; this is not the case in some countries, notably the USA. The duration of the withdrawal period The variable time to death after withdrawal of lifesupporting treatment poses major challenges for both the intensive care team and the organ procurement team and many potential DCD donors do not proceed to organ donation because they do not die within an appropriately short time period after treatment withdrawal. In the United Kingdom approximately 40% of potential DCD donors do not proceed for this reason and the uncertainty regarding donation often causes distress for the potential donor s family as well as logistical problems for the ICU staff and the donor procurement team. A long withdrawal period is often accompanied by a sustained period of haemodynamic instability and poor oxygenation, resulting in severe ischaemic injury to the organs that preclude their use for transplantation. In addition, an extended withdrawal time has important logistical implications in terms of maintaining an organ procurement team on standby with immediate access to an operating theatre. Consequently, consensus documents and clinical practice guidelines recommend a cut-off time if cardiorespiratory arrest has not occurred within a defined period of time, although this time period varies quite markedly and may vary according to the organ type being retrieved [19,22]. For example, the Australian guidelines recommend that for DCD donation to proceed, death must occur within 30 min of withdrawal of treatment for liver and pancreas, 60 min for kidney and 90 min for lung [19]. The evidence base for such stand down times is limited. Figure 2 shows that almost half of all potential DCD donors in the United Kingdom die within the first hour, of which 92% become organ donors, compared with just 3% in which death occurs beyond 4 h after treatment withdrawal. Within the first 4 h the organ retrieval team stood down on 67% of occasions. Although many of the potential donors who died beyond 1 h did not become organ donors due to prolonged functional warm ischaemia, in many instances the major factor was that the organ retrieval team had stood down in the face of donor stability. There maybe considerable potential for increasing organ retrieval rates by extending the period of attendance at the donor hospital, although this has logistical implications for both the retrieval team and the donor hospital. The UK national organ retrieval service have recently introduced minimum periods from withdrawal of life-supporting treatment before the organ retrieval team stands down in order to increase the number of potential DCD donors who convert to donation. Following withdrawal of treatment from a potential DCD donor, the cardiothoracic retrieval team is required to wait at least 2 h and the abdominal team at least 3 h for the onset of functional warm ischaemia (defined as a SBP <50 mmhg). Once the SBP has fallen below 50 mmhg (i.e. onset of functional warm ischaemia), the retrieval teams are required to wait for 30 min before abandoning the liver and pancreas, 1 h before abandoning the lungs, and 2 h before abandoning the kidneys as not transplantable because of excessive warm ischaemic damage. Predicting the duration of the withdrawal period If the duration of the withdrawal period for a particular potential DCD donor could be predicted this would help intensive care staff to better use their resources and manage expectations by patient Volume 18 Number 2 April 2013

5 Time to death in donation after circulatory death organ donors Bradley et al. Number of potential donors Potential DCD donors not proceeding to donation Potential DCD donors proceeding to donation <1 1 <2 2 <3 3 <4 4 <24 24 Not reported Time (hours) from withdrawal of life-supporting treatment to asystole. FIGURE 2. Time to death after withdrawal of life-supporting treatment for potential donation after circulatory death donors in the United Kingdom, 1st April 2010 to 31st March Data supplied by Rachel Johnson, NHS Blood and Transplant, UK. relatives, as well as enable more effective use of organ procurement teams and help to help maximise DCD numbers. Several attempts have been made to devise predictive models for early death after treatment withdrawal but it is important to appreciate that their general applicability may be limited by the nature of the patient demographics, selection criteria and the healthcare setting studied. North American studies have highlighted factors that might have predictive value for early death after treatment withdrawal [23,24]. Several predictive criteria were identified and as the total of the number of these UNOS DCD criteria met increases so does the percentage of patients dying within 1 h of treatment withdrawal [24]. In the United Kingdom, Suntharalingam et al. [25] reported a multicentre study that evaluated time to death in 91 potential adult DCD donors. After treatment withdrawal two-thirds of potential donors died within 2 h and three-quarters within 4 h. Most of those who became organ donors (83%) died within the first hour of treatment withdrawal. When the clinical factors associated with time to death were assessed, young age, high FiO 2 and non-triggered modes of artificial ventilation were all independently associated with a shorter time to death. The results of this study are in broad agreement with an earlier study from the USA [24]. Rabinstein et al. [26] recently produced a simple score based on clinical evaluation that predicts the onset of circulatory death in comatose patients with catastrophic brain damage undergoing withdrawal of life-sustaining treatment. Their scoring system was based on an earlier retrospective single-centre study they had undertaken suggesting that four easily tested clinical variables (absent corneal reflex, absent cough reflex, extensor or absent motor response and high oxygenation index) were each independently associated with death within 60 min of withdrawal of life-supporting treatment from patients with irreversible cerebral damage [27]. Apart from oxygenation index, none of the other non-neurological variables examined (including clinical measures of haemodynamic and additional measures of respiratory function) was independently associated with death within 60 min after withdrawal of life support [26]. When these clinical variables were evaluated prospectively in a multicentre study of comatose patients the authors were able to derive a predictive score for cardiac death in patients in a neurocritical state (the DCD-N score) based on the sum of points awarded for each of the ß 2013 Wolters Kluwer Health Lippincott Williams & Wilkins 137

6 Organ preservation and procurement four clinical variables. Absence of corneal reflex, absence of motor response and an oxygen index score of more that 3.0 were each scored one point and absence of a cough reflex two points. They found that a total score of three or more correctly identified 75 of 96 (72%) of those dying within 60 min and a score of 0 2 identified 75 of the 96 (78%) of those who did not die within this time frame. As the authors emphasised the DCD-N scoring system is only applicable to patients that die as a result of irreversible brain injury and the patient population that it was validated on was not restricted to potential candidates for DCD organ donation as it included, for example, patients with cancer and severe infection [26]. A recent single centre report from a large UK liver transplant unit analyzed all controlled DCD donor liver offers and associated liver transplant rates and then derived and validated models for both the prediction of cardiac arrest and liver graft usability [28]. Over the 10-year study period, a total of 1579 potential DCD liver donors were referred for consideration, of which 621 (39%) were deemed acceptable and of these 400 (64%) underwent cardiac arrest within the designated time period (1 h from withdrawal of life-supporting treatment). From the 400 liver donors, 173 livers (43%) were subsequently transplanted. Factors that predicted cardiac arrest within 1 h in this study were donor age less than 40 years, inotrope use and absence of a gag/cough reflex. The factors that were predictive for non-use of the donor liver were donor age more than 50 years, BMI more than 30, warm ischaemia more than25 min, prolonged stay in ITU (>7 days) and raised ALT. Using indices to predict time to death inevitably will result in missed opportunities for donation. Firstly, no index is 100% accurate and opportunities for organ recovery will be missed from donors who do die within an hour, and many more who die beyond an hour. Secondly, it presumes haemodynamic instability from the time of treatment withdrawal, which is often not the case. Maximizing conversion of potential to real donation after circulatory death donors It is important to emphasise that the time to cardiorespiratory arrest is not a measure of the degree of ischaemic organ injury incurred. Potential DCD donors may remain relatively stable for an extended period of time after withdrawal of life-supporting treatment and then rapidly deteriorate before undergoing cardiorespiratory arrest. Conversely, potential donors may experience profound cardiorespiratory instability following withdrawal of life-supporting treatment making organ donation unwise even though death is subsequently confirmed within 60 min [29]. A recent single centre analysis of procurement factors that were associated with biliary complications after transplantation with livers from DCD donors reported that of all the time periods during procurement, only asystole to cross clamp time (i.e. the true warm ischaemic period) predicted the development of biliary complications [20 & ]. Other variables examined, including the time period from withdrawal of life-supporting treatment to asystole and adverse haemodynamic changes in the agonal period were not predictive of biliary complications. Since 2004 our own centre has pursued a policy of adopting a minimum period of 4 h after withdrawal of life-supporting treatment from potential DCD donors before the organ retrieval team is stood down. Analysis of our DCD kidney donor programme showed that extending the stand-down time from 1 to 4 h leads to a 30% increase in the number of DCD kidneys retrieved and transplanted, without compromising transplant outcome [30 && ]. Of 117 potential DCD donors proceeding to kidney donation, 90 (76.9%) had cardiorespiratory arrest within 1 h, eight (6.8%) between 1 and 2 h, 11 (9.3%) between 2 and 4 h and a further eight (6.8%) beyond 4 h. A withdrawal period greater than 1 h was associated with increased donor instability (hypotension, hypoxia, oliguria and anuria, and acidosis) although not uncommonly donors with withdrawal periods of less than 1 h showed haemodynamic instability. Surprisingly, neither haemodynamic instability during the withdrawal period nor the duration of the withdrawal period appeared to adversely influence graft function at 3 or 12 months [30 && ]. First, these findings support the notion that the duration of the withdrawal period per se is not an important determinant of kidney transplant outcome. More controversially the results suggest that the presence of unfavourable withdrawal phase characteristics alone should not be a contraindication to retrieval of controlled DCD kidneys for transplantation. CONCLUSION There is considerable scope for further increasing the conversion of potential controlled DCD organ donors to actual organ donors. The duration and course of the withdrawal period is extremely variable and its significance to subsequent transplant outcome not clear. Clinical scoring systems for predicting which donors will die within an hour now exist but they are not yet sufficiently accurate Volume 18 Number 2 April 2013

7 Time to death in donation after circulatory death organ donors Bradley et al. and their clinical relevance is questionable given the recent data suggesting duration of withdrawal period may not be the critical variable in determining transplant outcome. Recent evidence suggests that using kidneys from DCD donors with an extended withdrawal period can be used to increase the number of transplants performed and provide satisfactory graft function. Future studies should aim to define clinical and physiological variables during the withdrawal period that can be used to maximize well tolerated use of kidneys and other organs from potential DCD donors. Long withdrawal periods are not an absolute contraindication to organ donation. Acknowledgements The authors have received research grants and honoraria for travel, accommodation, and registration to transplant conferences from Astellas, Novartis, Roche, and Wyeth; and research grants from Organ Recovery Systems. Conflicts of interest There are no conflicts of interest. REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 241). 1. Manara AR, Murphy PG, O Callaghan G. Donation after circulatory death. Br J && Anaesth 2012; 108 (Suppl 1):i108 i121. An in-depth review from the perspective of the intensivist. 2. Association of Medical Royal Colleges UDEC: An ethical framework for controlled donation after circulatory death: Consultation Koostra G, Daemen J, Oomen A. Categories on nonheart-beating donors. Transplant Proc 1995; 27: Bellingham JM, Santhanakrishnan C, Neidlinger N, et al. Donation after cardiac death: a 29-year experience. Surgery 2011; 150: Singh RP, Farney AC, Rogers J, et al. Kidney transplantation from donation after cardiac death donors: lack of impact of delayed graft function on posttransplant outcomes. Clin Transplant 2011; 25: Summers DM, Johnson RJ, Allen J, et al. Analysis of factors that affect outcome after transplantation of kidneys donated after cardiac death in the UK: a cohort study. Lancet 2010; 376: Qureshi MS, Callaghan CJ, Bradley JA, et al. Outcomes of simultaneous pancreas-kidney transplantation from brain-dead and controlled circulatory death donors. Br J Surg 2012; 99: De Vleeschauwer SI, Wauters S, Dupont LJ, et al. Medium-term outcome after lung transplantation is comparable between brain-dead and cardiac-dead donors. J Heart Lung Transplant 2011; 30: Zych B, Popov AF, Amrani M, et al. Lungs from donation after circulatory death donors: an alternative source to brain-dead donors? Midterm results at a single institution. Eur J Cardiothorac Surg 2012; 42: & Summers DM, Johnson RJ, Hudson A, et al. Effect of donor age and cold storage time on outcome in recipients of kidneys donated after circulatory death in the UK: a cohort study. Lancet This article from a National Registry shows that kidneys from old DCD donors do as well as those from old DBD donors, but tolerate prolonged cold storage less well. 11. Muthusamy AS, Mumford L, Hudson A, et al. Pancreas transplantation from donors after circulatory death from the United Kingdom. Am J Transplant 2012; 12: Mason DP, Brown CR, Murthy SC, et al. Growing single-center experience with lung transplantation using donation after cardiac death. Ann Thorac Surg 2012; 94: Harring TR, Nguyen NT, Cotton RT, et al. Liver transplantation with donation after cardiac death donors: a comprehensive update. J Surg Res 2012; 178: Detry O, Le Dinh H, Noterdaeme T, et al. Categories of donation after cardiocirculatory death. Transplant Proc 2012; 44: Reich DJ, Mulligan DC, Abt PL, et al. 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Transplant Int 2012; 25: This article shows that only the true warm ischaemic period (asystolic period) predicts biliary complications following DCD donor liver transplantation. 21. Souter M, Van Norman G. Ethical controversies at end of life after traumatic brain injury: defining death and organ donation. Crit Care Med 2010; 38:S Intensive Care Society NHS Blood and Transplant, and the British Transplantation Society: Organ donation after circulatory death. Report of a consensus meeting Bernat JL, D Alessandro AM, Port FK, et al. Report of a National Conference on Donation after cardiac death. Am J Transplant 2006; 6: DeVita MA, Brooks MM, Zawistowski C, et al. Donors after cardiac death: validation of identification criteria (DVIC) study for predictors of rapid death. Am J Transplant 2008; 8: Suntharalingam C, Sharples L, Dudley C, et al. Time to cardiac death after withdrawal of life-sustaining treatment in potential organ donors. Am J Transplant 2009; 9: Rabinstein AA, Yee AH, Mandrekar J, et al. Prediction of potential for organ donation after cardiac death in patients in neurocritical state: a prospective observational study. Lancet Neurol 2012; 11: Yee AH, Rabinstein AA, Thapa P, et al. Factors influencing time to death after withdrawal of life support in neurocritical patients. Neurology 2010; 74: Davila D, Ciria R, Jassem W, et al. Prediction models of donor arrest and graft utilization in liver transplantation from Maastricht-3 donors after circulatory death. Am J Transplant 2012; 12: Levvey BJ, Westall GP, Kotsimbos T, et al. Definitions of warm ischemic time when using controlled donation after cardiac death lung donors. Transplantation 2008; 86: && Reid AW, Harper S, Jackson CH, et al. Expansion of the kidney donor pool by using cardiac death donors with prolonged time to cardiorespiratory arrest. Am J Transplant 2011; 11: This article shows that extending retrieval team stand down time to 4 h increases the number of DCD kidneys transplanted with good outcome ß 2013 Wolters Kluwer Health Lippincott Williams & Wilkins 139