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

Abstract

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.