Dr Darrell Campbell (Ann Arbor, MI)
I remember when this really first started off, we thought, “Well, okay, we can do this maybe in the perfect donor.” We tried kidneys, and that seemed to work okay. And then some brave soul, I think it was probably Tony, said “We can try this in liver transplants.” And that seemed to offer something. And then pancreas, and now lungs.
So it has been a very rapid evolution, but it is not without a tremendous amount of work. But I think you should be very proud of this effort because it has saved a lot of lives, and that is what we are all trying to do.
So with that evolution, there are some questions I have. And I tried to pick a few questions that I thought would be of interest to the nontransplanters in the group, also.
That trigger time when most of the patients that you have were taken to the operating room intubated, and then you extubate the patient and expect them to die. But sometimes they do not die when you are there, their heart continues to beat, and much longer than we thought it would, and there are some agonal respirations or something.
So my question is, What do you do in that circumstance? What percentage of the time do you have to say, “Well, this just is not going to work. Take them back to the floor.” That, in itself, is a terrible experience for the family, obviously. We do not want that to happen. But what are the criteria that you would use to say either too much time has passed or this is just too much ischemia, we cannot tolerate that, we are not going to do it.
Then the second question has something to do with the liver transplants. You said that the overall results are not as good for liver transplantation. And for the patient who is dying on the list, that is not an issue, because anything is better than nothing. So it is not a question of whether they would take it or not. But for the patient who is stable on the list, my question is, when that call comes at 2:00 in the morning, what is the informed consent that you do or do not engage in with that patient to say, “Well, we have a liver. You are not dying right at the moment, but this liver is not going to work as well as from a brain-dead donor.” I think that is an important question. I would be interested to know how you handle that.
And then the question is, because we do know that the results are not quite as good in the liver transplant, do you try to steer those donors to lower Model for End-Stage Liver Disease (MELD) patients, for instance. Again, for the nontransplanters, that would be imply a healthier patient who is in better shape. Is that a strategy that we should embark upon?
And I have 1 more because I know it is hard to remember all these questions. The final question is, I know you can either cold store these kidneys when we take them out or we can pump them. And the University of Wisconsin has traditionally pumped the kidneys, put them on a pump, and pumped preservation solution through them. When you do that, you get data about flow. And my question then is, when you pump your kidneys from a donation after cardiac death (DCD) donor, are there flow characteristics that would say to you, well, this just is not going to work, we’ll discard these kidneys?
Dr Anthony D’Alessandro (Madison, WI)
We did develop a predictive tool. Although it is not perfect, it is a scoring system that is basically a respiratory assessment drive that we previously published. And based on this scoring tool, it is 80% predictive that a patient will, within 2 hours, expire. And we have also looked at the ones that we decided not to proceed on. And we miss about 20% of the donors, if you will, if we do not go on those.
And so every time we do a DCD donor, there is a discussion with the family, the physicians, the nursing staff, as to what the disposition of the patient will be afterward, because that patient does need to be cared for until they do expire, which is usually several hours later at most.
What we do find, which is somewhat different, I think, than what you referred to, is that families are quite appreciative. In fact, when the patient does not expire within that time frame, they are somewhat disappointed that there was not something that could come out of this tragedy that they could donate. So they do appreciate the opportunity and the effort that was made to see if their loved one could donate.
There have been a couple of other tools that are validated. There are some United Network for Organ Sharing (UNOS) criteria that look at not only respiratory drive but a number of other factors. But still, none of them are 100% predictive. So there are situations, as you mentioned, that, when we do a DCD donor, that patient will not expire within that time frame.
And we have a time frame that we pick that, beyond that, there is too much hypotension, hypoxia to make those donor organs usable.
As regards your question about informed consent, although informed consent is not required by any organization or UNOS for the utilization of DCD organs, because our data show a difference in outcomes, we have instituted, I believe for the last 3 years, an informed consent regarding biliary complications, and all the complications related to transplantation for DCD organs, that is discussed at the time of evaluation, and not at the time when we call a patient in the middle of the night.
And we find that is a very useful tool to discuss these types of livers. And what you mentioned is true, the results are not as good, but we are trying to determine not getting a liver transplant. What is the cost of that? And will a liver come in time before this patient expires on the waiting list?
And that gets to the next question regarding the MELD score and using them in lower MELD scores. There are emerging data, and our data as well, that suggest that you should not use these organs in patients with low MELD scores, that they may have time to wait for a higher quality liver to come along. And in fact, in our institution, we do not use the DCD livers now for patients unless their MELD is >18.
We always are stuck trying to put an organ, say, that is of lesser quality into a sicker patient, which has a much higher MELD score because we know that the outcome of the sicker patients is not as good, and the outcome of a marginal organ is not as good. So you combine them, you may not get a great result, but what you are doing is comparing that with whether that patient survives or not. I think that is important. So we do not use those in lower MELD scores.
As regards cold storage versus machine perfusion, as you know, we have been perfusing forever. I do not think we have ever stopped perfusing kidney transplants. And we do look at the flow characteristics. And interestingly enough, we discard very few of the organs that go on the pump. And usually we look at a resistance >0.4. Definitely >0.5, we would discard those. It also depends on how the kidney looks on the pump, whether it still looks modeled or not, well-perfused in those first couple of hours after we have put it on.
But by and large, I think the way we select our potential donors and the organs we recover, we have a low discard rate off the pump.
Dr Scott Gruber (Detroit, MI)
The vast majority of both the DCD and the DBD kidneys were machine perfused, although there significantly were less than the DBD group. What were your criteria for machine perfusion. Or, stated differently, which kidneys were not perfused? And do you think this difference positively affected the outcomes of the DCD group?
Second, did you expand the maximum warm ischemic time that was permissible for procurement of the DCD organs over the course of the study?
Third, was donor age significantly lower in the DCD group, both overall and in both of the 2 eras? If so, do you see this as a major contributor to outcomes?
Can much of the success of DCD simply be due to use of organs from younger donors with less other negative factors, such as comorbidities and pressers and so on?
Fourth, given the negative outcomes from your group, as well as the Northwestern group and others, regarding the use of DCD livers, what do you think is the future for transplantation of these organs? With these small numbers that you have, I think it will be difficult to determine how best to select out the appropriate donor and recipient combination for these high-risk transplants.
And then, fifth, was there a comparable proportion of SPK versus solitary pancreas transplants in the 2 groups? I think this could have had influenced your outcomes.
Finally, even though the difference did not reach significance, perhaps because of small numbers, the thrombosis rate of 11% is somewhat high in the DCD pancreas group, particularly for your program. Do you have any explanation for this, particularly in the absence of a difference in the incidence of transplant pancreatitis and acute rejection that might have contributed to the thrombosis?
Dr Anthony D’Alessandro
With regard to your first question on machine perfusion, the default is that all kidneys get put on the machine. And it is only because either the operating room is ready when we return, or there is vascular reconstruction that needs to be done, that we do not perfuse the kidneys. So there is no real intent to either perfuse or not perfuse any of the kidneys, although there has been some discussion in some groups because of costs whether we should just cold store standard criteria donors versus machine perfuse the other, more marginal, ECD/DCD donors, even though the delayed graft function rate has always been shown to be less with your machine perfuse.
We are actually going the other way in terms of warm ischemic time. We are decreasing it, particularly in liver transplantation. We would prefer that warm ischemic time to be 20 minutes, no longer than 30 minutes, based on our current definition. We are looking at sats and blood pressures and when they fall below certain levels to see if that may be more predictive.
The vast majority of kidneys were recovered in <1 hour, so we are still continuing with 1 hour for kidneys. We go to 2 hours, but there have only been a handful of cases beyond 1 hour that we have used.
There was no difference in donor age statistically between the DCD or the DBD groups that we saw.
I have not looked in the earlier experience. There tended to be, in the earlier experience, probably younger donors, as I recall how we went for donors in the earlier years. But later on, it has become the opposite direction. We have actually gone for more older donors than younger donors because of the changing donor population.
With regards to the liver and the negative outcomes, we continue to modify and vary our protocols to see. And hopefully, we can perhaps look at some of the techniques that we are using, modify those. And I think this requires some study in the laboratory to determine whether there are microthrombi that are developing, whether there is some other mechanism that is resulting in this ischemia, or are there other ways to prevent this ischemia in the donor before reperfusion.
There were no isolated pancreases in this series. All the pancreases were simultaneous kidney–pancreas transplantation. And I agree with you. The thrombosis rate, although numerically higher in the DCD pancreas, it did not achieve significance, but it did raise our concern that perhaps there is a higher thrombosis rate, although it is about 6%, I believe, in the DBD donors, not statistically different. But it does concern us that there may be something there that we have not really flushed out yet.