Director of the Penn Lung Transplant Center and Pulmonologist,
Dr. Maria Crespo, examines the critical factors pertaining to lung transplants. Some of these factors include evaluation, selection and the timing of the listing. She discusses the uncertainty of patients on ECMO for COVID-19 ARDS and the potential surgical challenges for these patients along with sharing early results of a lung transplant.
@PennMDForum Um I wanted to thank uh the symposium, the directors for giving me the uh the chance. I mean of uh talking to all of you again. Um So I will be discussing the critical factors which are uh involved in the evaluation uh selection and timing for listing some of the pros and cons and the ethical aspects that they are involved in that decision. Discuss the uncertainty of patients on EMA for COVID R D uh becoming long holders. Uh an initial consideration for land transplant, some of the surgical challenge in this uh population as well as uh review some of the early result of uh land transplant in patients uh with uh COVID uh land land diseases and also just share some of uh some of actually like uh experience uh at pen with these patients. So, over 364 land transplants, they have been performing in the United States uh for COVID uh 19 related lung diseases and most of them for A R DS and 39% that was for P fibrosis. And that basically represents 10% of the, of the increase in the boum. Uh from 2021 making. Uh COVID uh 19 lung disease. The the most common indication for land transplantation in this year. Uh after a P fibrosis and emphysema, the median number of land transplants for COVID-19 respiratory failure per center was uh in the range between 1 to 25. And also what we have seen with uh COVID is a tremendous increase in the ECMO support uh before the transplant as well as mechanical ventilation and the combination of EMA and mechanical ventilation based on the O P T N S RT R data, I mean, and that reflects the tremendous increase on the uh IC U resources that we have all experienced. So when you compare with uh 10 years ago, the ECMO to transplantation was uh 3% and it has substantially increased to 19%. The phenotypes of patients that they are referred to as for, for COVID-19 uh lung diseases. They are patients with uh A R DS that they are either on mechanical ventilation or uh failing to improve or they uh that they have uh left a significant residual fibrosis and hypoxemia. The timing for land transplants in the A R DS uh related with COVID has varied between the as early as 41 days to six months. And that is based on the, the published literature and it remains a very challenging to find what is the correct timing. There's a very scanty uh literature uh published on the, on the what is the land transplant outcomes in this uh in this population? And it is limited to very small case series and uh large cohort retrospective uh uh analysis of uno a database with only short term follow up. So, uh land transplantation indications for this population remains very controversial as there's no much actually like uh a robust data and uh and guidance to see what is the best uh the best candidate as well as uh we don't know what is the long term uh uh as well as uh uh as uh we don't know really what is the correct timing for these patients to undergo uh land transplantation evaluation and listing the decision that is very challenging that due to a robust evidence to help with uh in decision making, uh patient selection is key, we have just to make sure that the is that the correct age appropriate, the functional status of the candidate that the candidate doesn't have any, any concerning comorbidities. The time of we want just to make sure that these patients, they are not highly sensitized or they have very small chest cavities because that might increase the wait time to to be listed. I mean increasing the risk of dieing while waiting for a transplant. And uh we also check uh the B M I the frailty and the risk of renal failure infections is also in this patient, something that we need to uh to look very carefully what is the, the micro, micro data and make sure that they don't, they have not had any history of uh multiple drug uh um uh resistant uh antibiotics, uh bacterial infections. Uh The surgical challenge. Uh these patients, they have been infected before. They have had complications of empyema. They have had maybe like uh a hemo. And so they have a very bad plural involvement and due to the ECMO, they can have also uh a vascular complications, making the surgical, the surgical, the uh challenges uh much higher. And uh this is actually like something that whenever we present a patient, I mean, we always review the imaging studies with the surgeons. It's very important to have a multidisciplinary team involved, not just in the evaluation but just in the longitudinal care of these patients while they're waiting for the transplant and in the post transplant care, it's uh it's very important to have a clearly defined the course of care in these patients that they are on for COVID R DS with the patient if that is possible, but also with the family members. So we don't reach a situation of the patient is on to nowhere with no hope to survive back to this. In particular. There are patients that they are not a candidate for land transplantation, but also in patients that there were candidates. But now you have uh not to consider them anymore any longer candidates just because they have either either some uh some actually like a condition like maybe penal failure or liver failure. So the all of this leads to a significant from uh for the treatment er team and the ethical concerns that we have uh you know, experienced, I mean during the COVID uh in our IC US and uh and talking with uh other colleagues also, they have experienced the same things of ethical consents of disagreements among families and care, team over continuation and withdrawal of uh support. There have been several uh proposed uh criteria uh to for the selection of land transplant candidates for COVID. I mean, the first one, it was uh by the Toronto group. Then the S H L D COVID-19 task force also uh um publish some recommendations. This is from Chicago group, I mean, but they have a lot of things in common. I mean, we have just to make sure that that the patients have uh cleared the COVID infection. Uh They also, I mean, the age in here, I mean, in this group is probably a little bit much higher than some other centers. But we want also just to make sure that at least we allow the patient to have the time, you know, to, you know, to see if the, if the lung injury will recover. And in here in Boston for weeks. So what we did at pen is that we also created our own uh uh candidate criteria which uh was going to be very helpful. Uh when we were getting a lot of calls for from outside hospitals to try to treat as much as possible those patients. So our was 55 year old. We also use a minimum of uh four weeks just to give time uh to see if there were going to be some recovering. And we were actually finding that physiologically, I mean, no, no winning from the, as well as from, from as well as c uh changes uh consistent with uh with uh a lot of fibrosis and no indication that those lungs, they were going to recover. We also pay attention to the, the B M I, we needed to clear uh the the, the COVID infection. And then at the same time with uh our colleagues from transplant infectious disease, we were reviewing all the micro micro data, make sure that they didn't have a, a concern in actual like resistant uh organist infection. And with these, these patients, they have been on the ventilator and in the IC U for a long time. So, and the nutrition and the skin and the skin with the uh was going to be needed to be good. I mean, without any, any findings of the time, obviously single organ failure, you know, we were making sure that those patients, they were not highly sensitized and meet the other pen and transplant selection criteria. They have to be of paralytics and at least be awake and at least be able just to participate in some uh uh some rehab, I mean, with physical therapy. So and have some per rehabilitation that potential we were also doing virtual meetings uh with the outside hospitals as well as uh with the family just to go over. I mean, the what exactly was the uh the social support that these patients they were having as well as uh as the for them just to understand, well, what this was actually like in with land transplantation and uh some of the complications. Uh also, since the COVID vaccines started, we also mandated that patients that needed to be fully vaccinated. So what is the correct time for evaluation and transplant? And this is still actually like very challenging. I mean, when you're seeing this figure, I mean, since the patient has the infection has the pneumonia is in very high flow oxygen. And if things get worse, I mean, they are on mechanical support and then later on on. No, but they in here you don't want us to do it when the pay whenever is uh is the patient is in a, in a too early phase for recovery. But at the same time, you don't want to wait until it's too late. The patient is already very debilitated and they even actually like probably with the chances of losing that sweet spot window uh because they might have maybe now complications and they are now deemed not a candidate for land transplantation. So, uh it has to weigh the delayed recovery and against the risk of complications from prolonged uh support. So, there was uh there, there, there, there have been also some studies showing the what is actually like the, the progression from er A R DS to fibrosis and how the fibrosis look on, on the imaging studies uh with uh traction bronchitis and aural fibrosis. But there are studies showing that 38% of patients, they can have a complete radiological solution. Also, they have found that some of the risk factors of uh patients uh after the the COVID infection to develop fibrosis, they are the older they are when the, the how severe they have been the underlying uh illness, the longer I see you stay, the more prolonged mechanical ventilation with that probably reflects also the uh the oxygen toxicity uh accelerating mo the fibrosis in these patients. And also they have a history of smoking or alcohol use. So, I mean, they found that the majority of these patients, I mean, they, they can actually improve and remain stable. But the problem is is that we don't know who are the type of patient and how long it is going to to need actually for us to wait. There's some clinical trials now uh using the antifibrotic ages with uh as well as I mean, and uh we will see actually like if maybe some of these patients that they are able to be uh extubated and win from ECMO. But they are, they remain on very high flux again. They might probably actually like improve the lung function to the, to the point that they might not donate uh a an transplant. So this is a study from uh from uh from Dallas and they have uh 20 patients. Uh the uh the 10 of them, they were on support uh for less than 30 days and the 10 of them they were on the support for more than 30 days. And that is the ones that they define as a loan uh holders. So they, they started uh right away the plan evaluation and the only thing that there were three of them very good candidates for a lot transplant. One die, I mean, one goal and transplant, but the, another one also got, I mean, clinically uh better uh to the point that was extubated and decannulated. And after 10 weeks of uh support could actually like, uh not just clinically but also radiologically improvement. Again, this is actually like a very small co but opens the idea that, you know, this actually like can happen and they are as er some actually like a set of patients that they can improve actually like the, the lung function. So, in this Mayan analysis, they also found that that from those two cohorts that the long, longer, the longer uh they have actually like a better survival compared with uh with the other ones. Also, they found that by day 60, the improvement in the minute ventilation seemed to have plateau. So these are some of the surgical considerations, I mean, and the, and the complexities that that always uh um are very challenged. I mean, uh we know that the infection is uh these patients that are infected, they have more like uh very bad chest cavities, contrary to other transplantations, more risk of bleeding. Uh the risk actually because of the infection that during the, the longest plantation, that there can be some spill of infection and cause actually like a secondary afterwards. Most of the rest of them, they actually like because of bleeding and sometimes actually like size mismatch, they end up actually having to have their chest open after the transplant and require post. I mean, these, these patients also, there's a lot of concern because they go for a transplant, being debilitated uh due to the fact that they have been on prolonged mechanical support and IC U. And also we don't know about some of the future risk of uh of uh the uh and complications in these patients. So this is actually what the surgeons actually like uh like to see uh uh in the operating room whenever they open the, the chest cavity. And er, I'm not a surgeon, but it looks pretty bad for me. So this is one of the patients that uh we had a a that there was a complication. He was a 45 year old male uh COVID D R DS. Uh He was close to five months old on B B and they went a bi later lung transplant which was complicated by pulmonary, even thrombosis, which uh require repair. But then after we, he developed uh a, a very bad actually like necrotic uh lung. I mean, to the point that this man actually had to have a and he was having a lot of like uh and uh difficult to oxygenate. So he ended up having uh a pneumonectomy which later on actually he developed uh uh a and then, and then also like a right bronchial, the, the only the, the only Antos that he had left, he developed septic shock, I mean, and then ultimately, he was withdrawn from uh uh from. So this is uh so what do we know um er by now? So uh related with uh with the outcomes of uh on the land transplantation in patients with COVID. So this was the first uh the first publication and this is like uh 12 consecutive cases from four different countries. Uh And there were 12 patients, there was no much difference between the, between the patients in terms of age. I mean, in here, what you can see is that once the patient uh uh is actually like uh supported of there's 44 median of 49 days that it's you know, so very short until the patient is uh listed once the patient is listed. I mean, it's only like six, Say something. They get a transplant so they get a transplant are very quickly. The follow up is that was actually like the first, uh the first uh series. Uh the follow up was very short from those 12 patients. One of them died. Uh so they were 11 that they are alive and they have actually like um you know, complications that they are expected. So this is the same group also um compare er patients that they were on uh B B uh related with COVID and not COVID. And what they found is that this was the A match and the match group. And what they found is that there was no, there was no different differences in the, in the overall survival between the two groups but patients, so with uh COVID A R DS, they, they require more ECMO um they believe more. So they are more transfusions, higher degrees of P G D. They are uh they have actually a longer mechanical ventilation support large uh longer, actually IC U and hospital stay. And also one of the things that is important is that this the the this group also, they develop a renal failure that it was, it was actually like uh at the end, they didn't, it didn't recover at all. So this is also another group. Uh another study uh with uh Yeah. OK. Yeah. Yeah, hold on a minute. Um I mean, this is actually like the last uh the last study. Uh But again, it was only just based on the, you know, s data and uh it was very limited because only they have the, all the information from 100 and 83 patients. I mean, the follow up was very small. Uh And uh but I mean, it was a good result. So this is our first uh transplantation uh and that we have in the audience. Uh and he was only on, of course, for seven weeks. No, not really too much. I mean, but, but we knew actually that there was lungs there, there were no way that they were going to recover. Uh He's already two years, two years. And I'm, I'm actually like a very, very, it's my pleasure that he's my patient And he was the star of the day seven. This is uh another successful patient and this one I just wanted to make sure because that was the last one. So I put the first one and the last one. And this one actually, like he was actually for more than six months, actually, seven months on more support. And it took a lot of time because even he had so many complications in the outside hospital with a lot of uh you know, exploratory laparotomy with cholecystitis and perforated gall bladder. And they look at this I mean, he, he was the most complicated one but he's doing well. So uh I'm, I'm actually, I'm finishing. Yeah. So we evaluated more than 64 patients. Um but we end at listing the 24, but at the end, we only transplanted 21. And the if you look at the other slides, I mean, so any hospital mortality for the bridge was 6%. So it was not a very high and this is actually like some of the characteristics. Uh And so, in summary, uh we know that land transplantation uh for COVID uh is an acceptable treatment option in the selected patients with uh with COVID related A R DS uh er with uh reasonable short term outcomes. Uh The multidisciplinary team is, is important and there's still a greater uncertainty in determining the the uh the reversibility of uh the lung injury and the potential for lung recovery. And maybe we might need more, you know, research actually to find which are the phenotypes of patients that they will recover, but it might take a little bit of time. So, um so we know, I mean, I have discussed about all of this, the clinical management, the ses are highly center specific and transplant centers should determine what risk are acceptable for uh for the center. And obviously, we need longer, longer actually like uh a Coors. And uh and also just that to make sure that we have uh better data on long term outcomes that is lacking. And uh and I wanted, I wanted also to thank the people that they contribute with uh with the Atlan Transplant team actually for, for make sure that uh this actually like happen and, and that's it.