Pablo Sanchez, MD, explains clinical decision for unilateral or bilateral lung transplantation and he pros and cons of the alternative approaches to respiratory and hemodynamic support.
Good morning. Uh My name is Pablo Sanchez and I'm the surgical director for the land transplant team at the University of Pittsburgh. And today we're gonna be discussing the surgical aspects of a of a lung transplant. Well, we'll start uh defining first what is that that we consider a standard criteria donor. So when we get an offer, uh if the age of the donor is younger than 55 of course it has to be blood compatible without recipient, ideally it should have a clear X ray an A. B. G. Uh at you know, around 80 miles per kilogram of tidal volume. Uh People five and an F. I. 02. 100%. We're looking at appeal to higher than 300. These donors should have smoking history that list than than the 25 per year. We're looking at at the absence of significant chest trauma or infection. Uh in cases of aspiration of course, uh when we do a bronchoscopy and we have signs of food particles in their way, that's something we'll decline immediately. And then when our grants came from bronchial lavage is in this donor has um presence of bacteria, fungus or other significant number of white blood councils. Uh It will not comply with what we normally described as a standard criteria tonic. Mhm. The concern with this definition of the standard criteria is that only a few donors across the country will qualify to be used for land transplantation and that is why many centers now have extended those criteria and progressively have increased the number of donors that either older or have secretions in the airway. But those situations don't re accumulate or have changes in the X ray. As long as those X rays, As long as those changes are not the consolidation or pneumonia. Uh The the the ideal of extending this donor criteria is to increase donor utilization due to the present need to find um um suitable donors for our weighted listed patients. Recently a few technologies have come to the market and as you can see here different companies have invested in different versions of this technology. Uh And the whole goal of these technologies is to re evaluate or rescreen uh donor lungs under a control um temperature and profusion and ventilation uh with the goal of potentially isolating the organ from brain dead or shock or other um um physiological characteristics that the donor might be experiencing and under this better overall expendable conditions. See what is the true nature of that organ. Um If we abstract or try to summarize what are the uh technologies president. Even though they're different companies. The overall um application of ex vivo technology is is abstracted here in this slide. So you can either perform ex vivo at the center or you can perform Xbox facility a facility that is dedicated to do the XP professional for you if you perform it at the transplant center, what you normally do uh Or the two options that you have is one. You can procure the organs in a standard fashion and put it in a box transported back to the hospital and performed the expendable and profusion at your center before you transfer. The other option is the performance. We will and proficient during transport. And then um at the time that you're right to the center you gather enough data or you leave the lungs on the X ray machine until you feel satisfied with the data that you're seeing. The third option which is these facilities in which you can send the organ to after this has been procured this facility will perform acceptable and profusion and communicate the data back to you. And if the data is satisfactory meaning the physiology of the organized people, the X ray, the the overall oxygenation, then they would call the organ down packet again and send it to the transplant incentive to be transplanted here at the University of Pittsburgh. We uh perform a few of these or have access to a few of these technologies. We have the capacity of doing in our own institution, through the expendable and perfusion system. And overall what we do is to put a candle inside the pulmonary artery as you can see here and then a second cannula on the pulmonary veins as you can see here in green and an endotracheal tube here in the trachea. After these three structures coming calculated. Um we use we connected to this to this machine that we have in house which has access to all the physiology, physiological data and ventilate the organ and keeps it isolated during the professions in these organs. We can actually pretty much do have access to pretty much every piece of information that we normally have access during standard donation which is the bronchus copy through the electrical two or X rays or a Bgs through the different Canada that are connected to this organ. And as you can see here uh This is pretty much two very typical scenarios in which we can experience when we do an experiment and proficient here on on the left. This is a set of lungs that have been turned considering in the field but when the procurement team look at them, there were concerns on the consolidation on the right lower level as you can see here on the X ray and the oxygenation was a little marginal. So these lands were brought back and you can see the P. A Canada here, the left atrium Canada here and the endotracheal tube here. And these lands are being ventilated and and perf used through a period of the three at least three hours but sometimes up to six hours. And what do we do in these circumstances is that we evaluate the land compliance elasticity through time and as you can see here these lands progressively get less elastic less compliant which is a porcupine and at the same time the oxygenation continues also to decrease with non improvement or worsening of the pneumonia. So eventually these lands were declined and not transplanted here on the right, a very similar case. This Donald had a lower oxygenation in the field and we felt it had some bawdiness. So again you have the pulmonary artery cannula, the left atrial cannula, the industrial too. And we put him in the system. And as you can see, the elasticity remained stable at a good level for double Langenbrunner compliance of 80 and and the oxygenation progressively increase with an X ray that maintain itself clear or actually a little more clear than what it was at the beginning. So we proceed with transplantation in this case and these two cases kind of example exemplify the two polar opposites that we can see when we perform inexplicable and profusion. This is how the lungs will look when we're doing it. We have a professional system here that will be connected to a close secret. So these lungs will warm them up ventilated, expanded and keeping any system as I mentioned for at least three hours. But in many cases up to six hours to have a full evaluation of this order. As we have progressed in a land transplant history here at UPMC. Uh you know, at this time we have performed around 2300 land transplant programs. Land transplant cases since the inception of this program. And as the problem has change through times we have seen changes also in in the types of transplants that we performed in the times of diseases that we see more frequently. So uh you know the 1st 10 years from 82 to 92 you said that we will do very young patients most of the time were either the copts of pulmonary hypertension or cystic fibrosis. And and and and it was a very good split in terms of the Heartland transplants and single and transplants and double and transplants the second decade are recipients start becoming a little older And uh this is the era in which we were doing a lot of COPD and a lot of single transplants which changes in the land of issues score in 2005. What we have seen in our problem is the age of our recipient has significantly increased. And the number one disease that we are transplanted currently is pulmonary fibrosis. As you can see restricted. And the vast majority of the transplants that we perform at double and transplants. So this is what our program stands today. We're seeing more and more um an older population that requires transplant and more and more. These older population presents with pulmonary fibrosis in which many cases would have associated secondary pulmonary hypertension which require. And in most instances a double land transfer. The standard incision that we perform for for a double hand transplant is what you see here on your left, which is what we call a clamshell this incision goes from the left, the right to the left side and crosses the meatball here, the stern in which we split and later reconstruct. This is a very good incision because it gives us access both to the right land, left land and the heart. So in case in which we will need mechanical circulatory support during the transplant will have the heart radically accessible if we perform in a single and transplant, this is probably the incision that the patient will require, what we call an axillary for economy which is a lateral incision and allow us to perform uh the right hand transplant or left in cases that stand on the on the left and in many cases we can have access also to the heart, particularly from the right side if we require and circulatory support for a single and transport. Um The the need for her lung transplantation has significantly got down as as we have learned um that many of the things that we see on the right side of the heart, meaning a dilated right ventricle or uh the ventricle that is not contracting adequately is related to the amount of resistance that the heart is working against due to very diseased lungs. So in most cases in which our patients come to us with the need for Dublin transplant and severely dilated RV. These patients will undergo a hard failure evaluation and a land failure evaluation and we will define if it is absolutely necessary also to for the patient to undergo a heart transplant. As I say most frequently these patients, after we remove those disease lands the right heart will recover slowly function and these patients will do well just with the land transplant. Still in some cases heart lung transplantation might become a necessity. But this relatively rare procedure performed today in the United States will all say less than 50 Harland transplant performed every year. The natural sequence of either a single or double lung transplant will include an area anastomosis. As you can see here, we will announce the most what we call sequentially. We will do one line at the time. So what would happen is that we will take the either the right or the left leg out and then put the new right or left lung in the donor line because the airway is the most posterior uh structure. We will start with the airway in which you know, we're performing continuous anastomosis of the membrane nous. And then some corners teaches here to prepare their way to be open. And then we'll do a sequence of fears of a um um or use teachers to the cartilage. The next structure will be al pulmonary artery. As you can see it here. This is the veins veins we will do also a continuous suture of the pulmonary artery and finally we will finish up with our left HmD or pulmonary events which is an agent to HR anastomosis. As you can see in this picture at that point we will re profuse in the air the lungs. So we will open our pulmonary artery clamp and that will allow new blood to go into the lungs and the air removal there and all the preservation solution. And we will close aah and and start ventilating the land and that land will immediately start working. Um when we're looking at surgical complications, I think the the the early complications and the most fear complication under these circumstances is there were complications. Um different techniques through the year have been proposed as a way to reduce early complications. But at the same time the percentage of every complications um and how they are reported in the literature is pretty variable. As you can see we can go anywhere between 40% to 2%. And I think this is probably related to the way we identify and report these complications. Uh most of our patients undergo what we call an end to end anastomosis. And this has been a very safe procedure for us. And when we review our data, the percentage of airway to his senses, meaning both ends of the anastomosis disconnecting after transplant at least in our problem is less than 1%. Mhm. The kind of every complication that you will see, it will probably it will mostly be related to the time after transplant. Uh Early on in the transplant. The two more fear complications are the slaughtering of the airways, which will be related to the process of ischemia, re profusion injury or and as democracies, the Hisense meaning both ends of the anastomosis falling apart, which is related to surgical technique. And in addition to the amount of predniSONE that the patient was before transparent as we advance in time through the transparent, we can see other complications, some of them uh more frequent, which is some graduation at the level of our suture or some of them much much less frequent, like the Vanishing Airway syndrome, which eventually can lead to um to uh the need for re transplantation or bronchial um pulmonary artery or bronchi artificially, which again is very rare and very infrequent, but very little lethal complications. As I mentioned, you know the way that our world complications, Our reporter is extremely variable across institutions. So in in an effort to kind of uh um provides some ground for uh centers to report every complications uh uniformly uh the International society highland transplantation recently provided these guidelines in which we're looking at a more standardized way of reporting what we've seen. So we're looking at the ischemia necrosis. And then of course it's great bi locational extent, at the Hisense again by location, extent stenosis, location extent, or Malaysia of the airway anastomosis, this, in our opinion will provide a better way to compare different surgical techniques. Uh since all the other complications will be reported uniformly across the world. Mhm. Some other complications that we can see around land. Inland transplant cases though are extremely infrequent is in cases in which the arterial anastomosis or the arterial land is left too long. Either the recipient here or the donor are not shortened enough and you can have a kink of the pulmonary artery, which in all cases will require uh go to go back and repair the anastomosis at a more adequate length. And the same way that we see it in the pulmonary artery. We can also see in the pulmonary events if the Cavs are left too long, you can have qingqing on the pulmonary events which you know, will increase your your pulmonary capillary pressures that lead as you can see in this patient to pulmonary oedema and after it was corrected that that edema of the lungs, just because of any improvement in vocabulary pressure's better strain and allows this long to fully expand again. You have to remember that at the time we produce and cut our airway. We also cut in the lymphatic. So these lung transplant, his lungs don't have a good lymphatic drainage immediately after transplanting. There are a few um interventions that you can use during transplantation to reduce uh a stimulant profusion injury or primary graft dysfunction. One of the more frequent ones and one that still generates some some conversations and arguments across different centers is the use of inhaled nitric oxide. Uh In my opinion, the the use of nitric oxide in the transplant. It can have two effects. There is a lot of laboratory data showing that it can reduce or improved endothelial function leading to less poor primary graphics function. Doh clinical trials like this one from Toronto. Maybe we're under power to show that difference. Uh In in in in in in my opinion, the use of nitric oxide also can favor the uh more stable pulmonary artery pressure during the transplant. And in many cases will allow you to avoid mechanical circulatory support and perform the double hand transplant without the need of V. A. ECMO or the hard launching Again this study from Toronto unfortunately in my opinion was under power and that's why when you look at the data, there was not really any differences in clinical outcomes in the group that had uh nitric oxide supported and transplant. The group that didn't have uh support nitric oxide using nitric oxide. Mhm. So we still use it. Uh and as I say, the main reason for his use sometimes is uh want to stabilize the indo thallium potentially reduce the photograph dysfunction. So if we are doing a during a pump Harlem machine case will start. You get when the patient is induced well stop during the transplant and will restart it and re perfusion. And then when our patients get to the characteristic surgery. See you we transitioned the patient to call and immediately uh in cases in which uh have moderate pulmonary hypertension, we can also use nitric oxide as a way to avoid the need for cardiopulmonary bypass. As I mentioned it before soviet recently there have been uh an increasing interest on the best way to support the patient during the transplant, meaning most of the initial data in in in transplantation will clinical data will will demonstrate that doing the transplant without any cardio circulatory support lead to better outcomes. But as our patients are getting older and sicker and in many of these cases present to us with a need of a double hand transplant due to severe pulmonary hypertension or moderate to severe pulmonary hypertension in an older recipient, these patients require some level of security circulatory support to be able to safely perform the transplant. So it's unfeasible to do it any out of any support. Uh The the overall consensus within the medical the surgical establishment in land transplantation is a cardiopulmonary bypass is very useful but at the same time leads to some inflammation that can compromise you know or can lead to an increase in blood transfusion or to um the need for um um or the development of primary graft dysfunction. So with the improvement and the and the sophistication of ECMO technologies more and more centers have increased the use of in arterial ECMO during the land transplant as a way to reduce the amount of inflammation. Um The biggest difference between cardiopulmonary bypass and ECMO system is that, you know cardiopulmonary bypass is an open system. You have more surface of contact. You need full anti coagulation because of that there is a higher systemic inflammatory response. And in many cases you have a high a higher need for blood transfusions. Uh ECMO because it's the closest close system requires less anti coagulation. In theory reduce inflammatory response with a lower need for transfusion and that's why advocates of ECMO over cardiopulmonary bypass site. These differences as the one that favor very outcomes in this case. As I mentioned, several institutions have published. This is one of the earlier ones from Hanover in Germany showing that comparing when doing the compression of 30 patients and the cardiopulmonary bypass and 44 on ECMO. Uh the patients on on cardiopulmonary bypass required more red cells, more plate, less more need of postoperative dialysis. More need for post operative ECMO support and in addition the intro hospitalist mortality. Inter hospital mortality was higher in patients that underwent cardiopulmonary bypass. The toronto group did not see the difference in mortality or survival between the groups. They did see a higher transfusion rate more days on the event, a higher ICU and highland to stay. We have also published early on and we just went back to our data and the overall uh the thing that we have seen in our data now with over 100 and 50 patients on either the cardiopulmonary bypass or the Egmont group. This is the work that is about to be published is that yeah the cardiopulmonary bypass group sees a little more primary graft dysfunction sees a little more need for transfusion slightly higher need of days in the ICU. But all those different do not lead to higher mortality or higher. Um either right after transplant or within the one year. So in our opinion, in some cases, you know in which you needed uh cardiopulmonary bypass is still safe and necessary strategy to support patients safely during the procedure. Um There is the next step on on on on this development of application of technologies in in cardiopulmonary in the land transplantation with cardiopulmonary support which is should all land transplant be performed on V. A. ECMO. And there are some centers like the one from Austria and in Toronto in addition which independently if you have any indication or not for making for mechanical circulatory support, your transplant will be performed with V. A. ECMO. Um And and the advocates of these um of this proposal mentioned that, you know as you're doing the as you're doing the second Land the First Land when you're on video arterial ECMO doesn't see the full cardiopulmonary output which reduces the amount of ischemia. Very proficient injury that the first Land will observe. We have recently published this data and and and and as you can see in their opinion. Uh It's it's it's a safe and and relatively um um a novel way to go about carter supported patient to England transplant. Uh The true benefits of clinical benefits where haven't completely been elucidated or presented at this time. Though, the theoretical benefits are there, we haven't seen much in terms of clinical benefits of of these proposal of putting every single patient on via enigma for their planned transplant. Uh As you can see here, uh their use of ECMO doesn't add to the comorbidities when you compare with no ECMO. So but at the same time you don't see less uh primary graft dysfunction. As you can see here uh patients that are not supported at all. Uh 87% don't have primary graft dysfunction. So ECMO doesn't really add to that. So the strategy is safe. But as I mentioned, the benefits of this strategy are still to be elucidated and this is how they do it. We don't do it this way we don't put a cannula through the right age and we normally drain through the leg. These patients, in our opinion, that reduces the probability of sucking air through the right side of the heart. So you drain the right side of the heart and you put an arterial cannula. And then you do what we normally do sequential double hand transplant. And as you have the second line in place you ventilate it. I mean as you're doing the second land transplant, the first land that went in, it's ventilated, profuse with very uh non stress or low stress ventilation and profusion strategies, as I mentioned. Uh Well, the though there was a little bit of overall better survival, I think this comparison brought. It's a little unfair because we don't really know which ones were the no ECMO patients. So, uh based on this craft, it is an encouraging strategy though. I believe we still need to uh further investigate the true benefits of interpretive enigma for all. Um The Austrian group which has been very active on this uh suggested recently. Uh this this new party on online transplant, which will be uh you have a non optical donald long you can put it on acceptable in profusion, eventually improve the organ before transplant. Then you can support this patient with low stress strategies during the transplant. And and potentially leave these lungs on ECMO after transplant as a way also to reduce the amount of of ventilatory support. This in their opinion, leads to a reduced need for interpretive or drop or based oppressive support, which can lead to additional damage and eventually perpetuate primary graft dysfunction and later need for ECMO one of the other sizes other sources of donors that we can have in land transplantation. It's something that you might have heard as a donation after cardiac determination uh of death. Uh These are new, well, relatively new to land transplant though. They're not really new to other transplants. Um And these are tunnels that in most cases have devastating brain injury. But not to the point that makes them brain debt. But but to the point that is deemed non recoverable. Uh or uh some in some other cases somebody that has had and rest uh that either was witnessed around witness. So when we talk about donation after cardiac determination of circulatory death, we have two bigger theories which we have something that is an uncontrolled dcd meaning that came uh death to the E. D. Or came or there was an unsuccessful resuscitation at the in the E. D. Or a control the city, which means there is somebody that came to the hospital and and an injury was identified, the injury was the non reversible and the family eventually decided to move forward with donation by withdraw life support. These category three are Control This three. Category 3 are the more frequently using land transplantation. But even though the groups in Europe and in Australia are written in those places represent around 25% of their tunnel use in the United States is around 5% still uh uncontrolled the city in the United States has been a more logistically difficult donation strategy to implement, particularly in land transplantation. Mhm. Overall the data that we have seen with the use of control or because every three the city's has been extremely promising. These are many times very young donors donors that we didn't withdraw the with doing the withdraw life support. The lungs don't get injured and and they perform as in some cases significantly better than that that brain dead the city because these lungs didn't go through the process the injuries process of hormonal injury process of brain death, mm hmm. Another source of donation that has become very um encouraging lately, particularly after the the new uh far medicines and therapies that are available for hepatitis C is the use of hepatitis C positive donors. And uh the over the the overall differences here is that you can have a page donors that were exposed to hepatitis and they clear the virus. And at this point the only thing is that the antibody positive. So in these cases if you use these our strategy, it's just to transplant. Of course the patient has to agree to and and then monitor the net levels by pcr um In the recipient of these organs. And if at some point we see signs of hepatitis c infections treat those patients with new therapies. The probability of this happening is extremely low. Most of the data shows that it's less than 1%. We of the 20 patients that we have done our institution, we haven't seen any of them zero convert to hepatitis C. But if the not testing meaning that this donor did not clear the virus and the virus and the and the and the recipient is still very ironic. I mean sorry. And the donor is still very ironic. If the recipient consents to the use of this uh donor, we will treat them immediately after transplant. Okay, uh treatments are 98 98 efficiently state allowing patients to clear the virus with no problems. As you can see in this graph early on. Um many of the patients uh listed were not very kind. There was a lot of stigma around the use of hepatitis uh see donuts. But as as data has populated the literature and education has improved in our transplant programs. We see more and more of our way list recipients accepting organs for for from hepatitis C donors. So we see a significant increase in the number of our patients are actually consent for the use of these hepatitis C organs. Mm hmm. And that's uh pretty much that I wanted to talk to you today. It was a pleasure discussing some of these aspects of today today and some of the of the surgical aspects of uh of lung transplantation.
