Invited Response to Letter to the Editor by Callaghan Et Al, "following the Flow: Changes in Organ Preservation Methods Require Changes in Our Data Collection".

We appreciate the support by Callaghan et al1 of our recent article advocating for enhanced data collection by transplant registries to reflect the recent advancements in perfusion and preservation techniques. We believe the Letter to the Editor by Callaghan et al1 highlights an interesting and important issue when applying traditional terminology to normothermic regional perfusion (NRP): when does cross-clamp occur in an NRP donor? Cross-clamp has conventionally been synonymous with both vascular occlusion and the start of donor exsanguination and cold flush. Therefore, cross-clamp is a time point that is used to calculate the duration of 2 critical phases: (1) the length of donor warm ischemic time (dWIT) in a donation after circulatory death donor and (2) the length of cold ischemic time. As we illustrate in Figure 1 of our article,2 in NRP, cold ischemic time does not immediately follow the end of dWIT because there is a period of in situ perfusion. Therefore, should we define cross-clamp at the initiation of NRP when vascular structures are occluded to contain blood circulation to the thoracic and/or abdominal cavities, as Callaghan et al1 suggested, or is it the time of donor exsanguination and the start of cold flush? Or should we adopt new terminology that better describes these events? To our knowledge, there is no consensus or clear published guidelines on how to define cross-clamp for an NRP donor. Because this time is used to calculate the duration of various periods of organ ischemia, the definition has important implications for organ allocation, risk adjustment, and research. In the United States, the lack of consensus is leading to problems as illustrated by the following example. Kidneys are often allocated postprocurement. If cross-clamp is defined as the start of cold flush in an NRP donor, then dWIT may exceed many transplant centers' acceptable length of dWIT. In the United States, centers may have predefined dWIT filters in the online allocation platform (DonorNet) that automatically decline these organs, incorrectly excluding patients from transplants. However, if donor cross-clamp is defined as the start of NRP, then the ex situ time will be falsely prolonged. DonorNet allows for 1 "cross-clamp" time and does not have the versatility to record multiple time points, which is necessary for NRP donors. We are aware that some organ procurement organizations may actively change what they record as "cross-clamp" when allocating kidneys so as to avoid automatic declines based upon falsely prolonged dWIT. However, after kidney distribution has occurred, the organ procurement organizations change the cross-clamp time so as to accurately reflect the organ ex-situ duration. We propose calling the start of NRP "in situ perfusion start" and the end of in situ perfusion and the start of cold perfusion "NRP-cross-clamp." We acknowledge that in Table 1 the definition of total ex situ time could be amended to be the time from the start of donor exsanguination and cold flush (what we termed "NRP-cross-clamp") to reperfusion in the recipient.2 Total preservation time is the sum of in situ and ex situ time. This discussion highlights that the adoption of new preservation and perfusion techniques have introduced new time points that cannot automatically assume the old time stamp definitions. We urge national and international organizations to formally adopt terminology and definitions so that there can be alignment throughout the transplant community.