Speaker 1the average survival for a lung transplant with both lungs so bilateral lung transplant is about seven years compared to other organs that surpass that I mean they're 20 years plus especially when you're looking at kidney liver so our organs really struggle long term and one that's because we have just like you mentioned the lungs have chronic exposure so not only are they chronically sensitized but they're chronically exposed to different viruses molds bacteria ntm is a problem and so because of all that you have a cascade of problems in the future we have to have really high program for whatever immunosuppression you're using goals and these levels that we target come with side effects welcome to
Speaker 2critical care time the podcast for everyone who cares for the critically ill I'm one of your hosts Dr Cyrus asking here with my illustrious co-host Dr Nick Mark I don't know about illustrious but but I am here yes and your internet connection at least seems to be working so that makes for one of us I guess that's true
Speaker 3uh listeners may not be aware of this but Cyrus apparently lives in a cave where there's very poor internet connection which complicates our
Speaker 2recordings yeah um it's just I've heard it's good to like operate out of a Faraday cage if you can can do that at all
Speaker 3so we were saying it would be more efficient to wrap the tinfoil around your head than around the router but I do that too
Speaker 2though I I do have a tinfoil hat that I
Speaker 3wear good can't be too safe you don't want to let the the 5G vaccine waves into your brain no I don't
Speaker 2yeah but I get great cell signal at least no internet but great cell signal there's always that yeah
Speaker 3all right man so what are we uh what are we talking
Speaker 2about today great question Nick so one of the areas of medicine that we really haven't touched on yet here on critical care time is transplant medicine and as you guys know transplant can be complex and really sick so big hospitals and academic centers they often have teams and special ICUs dedicated to the care of these patients who really do benefit from it whether it's kind of peritransplant or decidedly post yeah and
Speaker 3I think you know there's there's a lot of complexity to this right there's the underlying disease there's the immune suppressive meds there's potential complications of the transplant like rejection and then there's all the infections that these people can get I I also think it's worth pointing out that just because this happens at these you know Elite medical centers it doesn't mean that people who have received a transplant don't get sick and wind up somewhere else or people who need a transplant go to another center I need to get transferred so I think regardless of where you work this is probably a high yield episode for our listeners
Speaker 2I love it and of course we had to start with our two favorite paired organs the lungs uh no offense to the nephrophiles but uh you know you can't
Speaker 3that's not my favorite pair organ but I'll
Speaker 2stop there yeah fine fine fair enough uh this is uh now turned into critical care time after hours I'm glad to be a part of it yes well you know Nick's seems to be really intent on losing as many listeners as possible on a weekly basis and yet it's not working so okay despite my efforts right well okay thanks for that Nick we're going to be focused on lung transplant today and we are very excited to do it with a couple of amazing guests the first that I'll introduce is Laura Jones who's an assistant professor of medicine specializing in lung transplantation as well as kind of pulmonary and critical care medicine she's here uh nearby uh me anyway at UT Health San Antonio as is our other guest so Dr Jones did complete her fellowship and training in pulmonary and critical care medicine followed by a dedicated lung transplant fellowship and she's now practicing as I said in San Antonio her clinical and research interests focus on post lung transplant complications immunosuppression management infection frailty uh with multiple national presentations in a recent publication at ishlt and chest so super excited to have you here Laura um and then Nick if you want to take it from
Speaker 3there yeah joining Laura uh and for the first time on our show we have a surgeon Dr Jason Goucher a thoracic surgeon at UT San Antonio his focus is on lung transplant and thoracic oncology he serves as the surgical director of their lung transplant program and before moving to sunny San Antonio he spent nine years at I guess also Sunny uh Washington University in St Louis so anyway great to have you both on the show with us thanks Nick all right now
Speaker 2we've introduced our guests and the topic let's get on with the show all right so uh again welcome to both of you uh welcome to the show so excited to have you guys here before we really get into the meat and potatoes here uh Laura maybe you can share a little bit with us and with the audience about who you are and how you got interested in transplant
Speaker 1medicine yeah thanks so much for the introduction and thanks for having me on your podcast I feel absolutely honored to be here with you guys so I was drawn to transplant medicine for many different reasons but really two reasons stick out one I was really lucky early in my training to have incredible role models that have followed me throughout my Fellowship and I work with closely now as a faculty and these people have showed me how to um work with patients who are technically um complex in a demanding role high-stakes medicine and doing all this with humility and compassion and they're the reason why I joined the field the reason why I stayed here is for the patients these patients live in constant space of uncertainty and hope at the same time and they let me into these lives during their moments which are incredibly vulnerable so this is something I don't take lightly I find it incredibly rewarding and I'm so lucky to be a part of their journey that's
Speaker 3great yeah um Jason do you want to follow suit you want to tell us your superhero origin story or I guess being a surgeon there's a non-zero chance that you could have a super villain origin story I'll let you uh disambiguate why didn't
Speaker 1I get that question my answer is
Speaker 4not gonna be nearly as good as Laura so it doesn't help that case but yeah so I I went into medicine for the same reason that a lot of people do um nothing too unique I really like science was good at it and I wanted to help people so it seemed logical um and nobody in my family was medical so I didn't really know what I was getting into and and never thought about surgery until one day uh when I was an undergrad a cardiothoracic surgeon offered to have me uh shadow him in the OR I figured why not and I looked you know looked it up the night before uh to figure out what that specialty kind of even was and I went in the next day and was just blown away and I decided at that day I was going to be a CT surgeon and and I I entertained some other specialties along the way and uh somewhere in my path of training I got really interested in thoracic oncology and lung transplantation so that's where it's been most of my uh time now is treating those two
Speaker 3conditions great well um two experts uh two two related but slightly different perspectives so we're really excited to have you guys on Cyrus has done a great job laying out kind of a flow for us where I think what we'll do is we'll kind of start with a case and sort of walk through from the pre-transplant peri-transplant post-transplant and kind of see how the story unfolds so Cyrus why don't you take us away
Speaker 2oh thanks Nick you really that was very interesting okay uh so let's uh let's get on with it uh 54 year old man with end-stage fibrotic lung disease he's got a UIP pattern on CT progressive despite antifibrotics consistent with IPF uh he's also got chronic hypoxemic respiratory failure as a result he's on high flow nasal cannula and unfortunately he's in the ICU he's got worsening dyspnea rising oxygen requirements so a patient that we're probably all familiar with unfortunately um he's got no significant extra pulmonary organ dysfunction his BMI is 27 he's got no active infection and he really does have a lot of bacteria in his blood so he's got a lot of bacteria in his blood so he's got a lot of bacteria in his blood so he's got a lot of bacteria in his blood so he's got a lot of bacteria in his blood so he's got a lot of bacteria in his blood infection and he really does have some strong social support big family um you know and so he's in a good spot there so given the focus of the show you know we're not going to delve into the the list and the nuances of what makes for a good candidate in the ambulatory setting but we'll say that the patient's been listed for a couple lungs he's been awaiting transplant and so we'll kind of start with the the pre-transplant period here and some of the bridging decisions that we might have to um consider I'll pose this to both of y'all maybe first to Laura and then next to Jason this patient shows up in the ICU what are the key factors that you're going to be assessing to help you decide whether they actually are going to remain a viable lung transplant candidate or whether they might have to be
Speaker 1delisted yeah I think so to answer this question it really helps first to clarify what we mean when we say a patient is in evaluation when they're listed when they're status 7 or when they're delisted some of those are pretty obvious um but the distinctions really matter to us and they really matter when the patients are in the unit a patient in evaluation means that they have met ISHLT criteria to get a lung transplant but they're still completing testing consultations so they're not technically on the transplant list once that process is complete the multidisciplinary transplant committee reviews the case they decide whether to list defer or decline and if a patient is listed they can actively receive donor offers status 7 means that the patient was listed but they're temporarily on hold because of a potentially reversible issue and then delisting is different that's when a patient was previously listed is removed and that's usually because of an irreversible condition so when a listed patient lands in the ICU I usually ask myself three questions because our team has to decide if we should keep the patient patient listed or not so the first thing I ask myself is is the reason for the ICU level of care a progression of their underlying condition or is it just because of the patient's condition or is it just because of the underlying condition or is it just because of the underlying disease and if the answer to this is yes then it's easy they remain listed assuming everything else is normal and we optimize them as much as possible for surgery while they're awaiting offers And this means, if necessary, we put them on hyponasal cannula, we put them on non-invasive positive pressure ventilation if needed, mechanical ventilation via tracheostomy, or ECMO until they get transplanted. So whatever support they need, we do it. The next thing I ask myself is, if it's not related to their pulmonary disease, is the issue reversible? The most common reasons why we place someone on status 7 include things like major medication changes. So if they have an increase in their steroids, and for our program, anything greater than 20 milligrams means that we temporarily put them on hold. If they're on vasopressors because they're in the midst of cardiogenic or septic shock or something like that, we'll also put them on hold. And then other common medications are things like opioids, benzodiazepines. And for some reason, they had a PCI and they're on Plavix or some sort of antiplatelet therapy, we'll put them on hold as well. And then any new organ dysfunctions such as renal failure, GI bleeding, especially an ability to ambulate, we'll put them on hold temporarily until we can figure that out. And then the third thing I ask myself is, can we clearly define what recovery would look like and how do we get there? So occasionally, the reasons I listed above, they can become really complex. For example, a patient may have new GI bleeding due to a peptic ulcer, and this can complicate timing of relisting. So we can't just say, "Oh, I'm going to have to go to the doctor and get a new GI bleeding." We can't just say, "Oh, I'm going to have to go to the doctor and get a new GI bleeding." Most importantly, we have patients that are living with little physiologic reserve and one complication can tip over their compensation and they can spiral into what I think of as a frailty cascade. So they stop moving, they stop eating, they lose muscle mass, sarcopenia sets in. Once this happens, outcomes are consistently poor and this almost not always but often leads to delisting unless there is a possibility of recovery there. That said, if a patient is admitted for progression of their lung disease and they go into this frailty cascade, we're going to try to do everything we can to get them out of it, especially if it's just because of their lung disease. Candidacy in the ICU is never static. It's a continuous reassessment of risk, reversibility, physiologic reserve, and a decision that we make as a committee with multidisciplinary discussions.
Speaker 3What a great overview. I really like that summary of it. And I think, you know, there's already sort of a call to action evident there, which is that as the people caring for people who are listed in the ICU. It's really important for us to do what we can to avoid that frailty cascade. I'm sure we'll come back to this point. But, you know, we often harp on this show about the importance of nutrition, mobility, weaning from devices as soon as possible. And I think you just emphasized why. And we often harp on this show about the importance of nutrition, mobility, weaning from devices as soon as possible.
Speaker 4They're full of T cells and B cells. cells, they mount incredible immune responses, as you all have seen in ARDS. I mean, that's a tremendous inflammatory response that most organs couldn't do. And so the lungs are just highly
Speaker 1immunogenic. Yeah. And I think to your point, the average survival for a lung transplant with both lungs, so bilateral lung transplant is about seven years compared to other organs that surpass that. I mean, they're 20 years plus, especially when you're looking at kidney liver. So our organs really struggle long-term. And one, that's because we have, just like you mentioned, the lungs have chronic exposure. So not only are they chronically sensitized, but they're chronically exposed to different viruses, molds, bacteria, NTM is a problem. And so because of all that, you have a cascade of problems in the future. We have to have really high program for whatever immunosuppression you're using goals. And to these levels that we target come with side effects. So a lot of our patients develop side effects to the immunosuppression agents that we use. We use a three-prong approach of a calcineurin inhibitor. So tacrolimus is what most people use. Cell cycle inhibitor is mycophenolate. That's what most people use. And then prednisone. But all these medications come with side effects and toxicities that the patients deal with long-term. Almost every single person gets CKD. And so we have to be very careful about that. Every single person gets hypertension, hyperlipidemia, diabetes, and these kind of wear and tear the body. But this is long-term, not ICU acute things. The transplant itself is an eight to 10-hour surgery. And almost every single person goes on some sort of support, at least at our institution. We take really high-risk patients who come in with group three pulmonary hypertension or just group one pulmonary hypertension. And they require bypass or ECMO perioperatively, which comes with its own set of complications.
Speaker 3So I really want to go back to our case. And yet you guys keep saying such great things that I feel like we have to talk more about. So just to expound on a couple of points you both made there. So number one, you listed the sort of three sort of tiers or three, I don't know, like tines of a fork of like immune suppression. I always think that like this is something that everybody needs to know. And I think it's really important to think about it. And I think it's really important to know because everybody needs to watch for this in the sense that like if somebody who's a lung transplant recipient comes into a small community hospital in the middle of the night, it's really important to be like, okay, this person's had a lung transplant. Where are these three meds? And this is probably not the kind of thing that you're like, oh, the team can sort this out in the morning. Like these are not meds to wait on. Is that right?
Speaker 1Right. Yeah. And, you know, this stuff can get so nuanced because say you have a patient who's 10 years out from their transplant and has recurrent skin cancer, sometimes they won't be on CellCept and they're, they may be on tacrolimus, but their goals are really low because they're having some sort of toxicity to them. So if you don't see a medication, it may be because there's a reason it's not there. But to answer your question, most patients, especially within the first year, are going to be on three medications for immunosuppression. Gold standard is tacrolimus. And compared head to head with cyclosporine, which is an agent we used to use and use for the first few transplants. But it's shown over and over again to be superior in terms of preventing rejection. And so almost always our patients will be on tacrolimus unless they can't tolerate it. And then the alternative will be cyclosporine. Very rarely, you may see someone on a combination of tacrolimus and rapamycin. And we do that to lower the tacrolimus goal so that the patients have less toxicity. We do that specifically in patients with malignancies or those patients that may have CKD or other toxicities to tacrolimus.
Speaker 4To kind of help frame how you think about it, these immunosuppression strategies have been adapted from other solid organs, namely kidney and liver. So they're very similar. So like if a patient gets a kidney transplant or a liver transplant, at least in my understanding from my training, unless things have changed, it was a calcineurin inhibitor like cyclosporine and tacrolimus. It was a prednisone and cellsept. So it's very similar for lungs.
Speaker 1Yeah. So the cell cycle inhibitor, if for some reason they can't tolerate mycophenolate because they develop neutropenia or GI side effects or what have you, the other alternative is Imuran. So if you don't see cellsept on board, usually you'll have Imuran there. And then prednisone is like the nuclear bomb of the immune system that every single organ loves and the lung specifically. So our patients are on it lifelong. And the dose differs based on programs. Some do 10 milligrams lifelong. Some do five. Just kind of depends on the program.
Speaker 2Excellent. You're like a little fellowship, a mini transplant fellowship in an episode. I'm learning a lot.
Speaker 1I mean, you guys ask the questions. I'm happy to talk about it.
Speaker 4These patients are really good at remembering their medicines. So obviously when you're in the critical care setting, you get a lot of patients, patients that aren't able to recount their history as they normally will. But if you talk to them and they're in their usual state of mind, they're going to be able to tell you because these are people that are already been screened and determined to be reliable and have good social support and be able to keep up with things.
Speaker 3I think that's a great point. And I think also my experience with transplant patients and particularly lung transplant patients is they know who to call, right? So if there's a doubt, it's not like, oh, we'll sort this out after the long weekend. It's like, they know who to get in touch with today to answer this question. So this person is in the ICU with acute hypoxemic respiratory failure. They are kind of perhaps on the verge of needing invasive mechanical ventilation. I'm curious to get your take, maybe Laura first, and then Jason, you know, when you're, when you're considering having to intubate somebody in this situation, like what, what additional considerations are there?
Speaker 1Yeah, I'd say honestly, for our lung transplant candidates, mechanical, invasive mechanical ventilation is almost always a liability. The caveat here is a patient on mechanical ventilation via tracheostomy where the explicit goal is to keep the patient awake, interactive, and actively rehabbing. And what I've learned over time compared to my early training, where we knee jerked put anyone who is intubated on propofol and fentanyl is how harmful over sedation is, especially in our patients. Sedation drives delirium, delirium drives immobility, immobility drives deconditioning and frailty. And again, once that cascade starts, patients can miss their transplant window. Our ICU does an amazing job minimizing sedation and keeping even intubated patients via like ET tube walking down the hallway, which blows my mind, but we do it. That said, despite our best efforts, patients can still lose their tremendous amount of ground and muscle mass if they're intubated via ET tube and on mechanical ventilation. They lose endurance and cognitive clarity. And so we always try to avoid it as much as possible. So, you know, I've been asked in the past, well, should we like, what kind of ventilator settings do you want in this patient who has ILD and their peak pressures are 65 and we're really scared, you know, because their tidal volumes are down to 150 and how do we prevent ventilator associated lung injury? And I hate to say this, and maybe I shouldn't say this on y'all's podcast, but while ventilator associated lung injury is always something to respect in our patients with end-stage lung disease who are actively awaiting transplant, I've largely accepted that the native lungs are already lost. And my bigger concern isn't about injuring the lungs that are about to be replaced, it's injuring the rest of the patient. And honestly, to be clear, I think I say that and I like stand on a hill and say this on rounds and then the intensivists are like, okay, yeah, Laura, and then they go and like fix the ventilator and make sure that they're on protective lung settings and are doing all the best things for the patient. But, you know, I stress less about the lungs that are already really injured, especially when they're about to get a lung transplant. What they need is a transplant.
Speaker 2Yeah, Laura, that's great. And I think there's a couple of things I'm, you know, reminded of. So we have done a couple episodes now. We've done one with Callie Dayton on mobility in the ICU and being a mobility champion. We've done the one with Wessie Lee on the importance of, you know, recognizing delirium in your patients. And those are kind of two significant issues, debility and delirium that can really, really cause problems with your ICU patients that are awaiting transplant. These are typically not short stays in the ICU either. So they're at incredibly high risk for all of these issues like, like Laura, you'd mentioned. We hope to in the near future, I've actually got a physical therapist who does a lot of physical therapy with ECMO patients in town who I want to bring on and talk about specifically sarcopenia, rehab, you know, in the ICU, how do you keep these folks moving? Because it is just so, so important. It's like you just, the idea of trying to do the best for someone and take care of them only to sort of like hurt them ultimately in the grand scheme of things is just really heartbreaking. And I think it's important for our audience to recognize that potential when they're taking care of these patients. So with that being said, you know, maybe Jason, I'll turn to you and say, okay, well, you know, we've done this, that and the other. And ultimately we decided this patient needs to be on ECMO. And fortunately their heart's working well but they do need to be on on vv ecmo and so how did i come to that conclusion let's say you know how how might you come to that conclusion and what makes a candidate either good or poor with respect to using ecmo as as a bridge as we would in this circumstance
Speaker 4well for the reasons that laura laid out uh you know i would second that often being mechanically ventilated is is a liability and so if this is something that's going to be reversible we can probably get them better then then we'll intubate but otherwise if we think they're they just need to go then down the direction of getting a transplant then we just uh we'll often just put them on on ecmo and and we can talk about you know awake ecmo versus intubate them and then place them on it there's some things to discuss there for sure but whenever it's time to step up their treatment and um and we elect that ecmo is the best option i i think you have to ask yourself the question do they need do they need to get this done now quickly to save them and rescue them or do we need or can we do this more uh more electively and think about the best way to configure them to promote their mobility the gentleman that i just transplanted last weekend was was you know i mean incredibly sick nearly going to arrest had to be placed on ecmo urgently you know that's not a patient that you should take to the cath lab and use fluoro to do an advanced configuration you got to get them on smoothly and smooth as fast and so that's usually femoral femoral venous ecmo if a patient has profound hemodynamic abnormalities you're worried about their heart namely their right heart in the setting pulmonary hypertension va ecmo usually groins is going to be the quickest way to go and then once you get them stabilized you can ask questions about how that can be optimized
Speaker 3excellent i think there's a lot of great points there yeah i too i've seen ecmo used as both a life-saving tool and as a bridge to transplant tool and sometimes it's the same and sometimes it's sort of one and then the configuration is different and sometimes it's the same and sometimes the configuration is changed to facilitate the other for centers that are ecmo centers that are not transplant centers any thoughts on like what what they should be doing to to care for these patients you know because i mean presumably the hope is cannulate them save their life and then facilitate a transfer any any considerations there i would just
Speaker 4say that there's a tremendous amount of lives that can be saved with that and and that alone and that is how we are helping save a lot of people's lives is because they were bailed out of trouble at another hospital and so the the goal there is just to get them alive and get them somewhere that can that can you know figure the rest out even even if they're not transplants not even on their radar um just just getting somebody on ecmo is often a safer way to transplant i mean to transfer them and then they can get the work up once they're at a transplant center i think in in those settings um i i think femoral ecmo is usually the easiest way to go be that vv or or va but we've certainly had transfers from other hospitals with advanced configuration strategies and and i i applaud that but um that that's you know just center dependent i think the most important thing is to keep them alive and have them safely transferred and
Speaker 2jason you know this isn't uh obviously an ecmo episode per se but i was hoping you could maybe unpack some of those specific configurations briefly just so that our audience has at least heard some of the terms and and know what they're talking about sure yeah absolutely
Speaker 4so you know whenever we look at placing somebody on on vv that's generally because they have inadequate ventilation and or oxygenation and their hemodynamics are okay uh whenever we talk about lung transplant patients they're the high afterload on the right heart from pulmonary hypertension can put folks in a cardiogenic shock and we've all seen that and in that case sometimes vv can can improve that but most of the time if they're in shock they just need to be placed on va and uh and so once they're on va you know that's not something that we want to continue for very long uh if we can avoid it um we certainly do place patients on the wait list who are on this but there's risks of being on va ecmo um namely if you're cannulated in the groin with the femoral artery there's a very high risk of of limb ischemia which carries a really substantial uh chance of mortality obviously very high morbidity so um we'll often try and reconfigure folks who are placed on va urgently to um something that's going to decrease our risk of limb ischemia and allow them to mobilize in the lung transplant population that's often vpa where we'll have some sort of drain in the svc ibc um usually a multi-stage cannula drain in the right atrium ibc svc and then we have another cannula going from from the left or the right arm or neck into the pulmonary artery as the uh outflow and this unloads the right heart and allows folks to mobilize in the same way that that you know they would if they were on traditional vv or had one of the advanced configuration strategies whenever they're on vv ecmo um they certainly can ambulate with uh bilateral femoral veins being cannulated we see that that a lot but uh it can cause some get up and down when they sit, those cannulas can be positional. You can have issues with recirculation. You can have the cannulas advance too far and go through the interatrial septum. And so I've become a fan of either moving one of those to the neck, right IJ femoral, or using like a dual lumen cannula, like a Crescent or Avalon cannula in the right IJ, so that you can drain the SVC, IVC, and then flow towards a tricuspid valve. That's a really nice way to configure people so they can mobilize.
Speaker 3I also love that configuration for mobility in these folks. Absolutely. And I also love your point too about how you can start with one configuration to save their life and then adjust to another configuration to optimize for mobility and other factors, which is ultimately what's going to save their life.
Speaker 4Right. I think most of the time that that's the right answer, is to do what's easy first, get them out of trouble, and then optimize it later. You're on the front
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Speaker 2now back to our show. So in this case that
Speaker 3we're talking about, this is somebody who's already listed. But you guys have mentioned sort of an edge case that comes up, which is somebody whose illness has happened so quickly that they are not even evaluated prior to their becoming sick. You know, in these folks, ECMO can be a bridge to transplant, but it can be a very uncertain bridge. Laura, how do you navigate the sort of ethical considerations surrounding that when you might be building a
Speaker 1where, essentially? Yeah, I mean, gosh, these cases are so difficult. They're difficult for the patients, difficult for the family members, incredibly challenging for all of our teams, you know, the ICU team, the transplant team, C2 surgery team. And usually when we cannulate, it requires multidisciplinary input. But you do have the rare case that comes into the emergency department, saturating 20% with clear ILD on their x-ray. And they get cannulated to save their lives. And then, you know, we're stuck with a patient with lots of question marks, and they're on ECMO. And we've kind of mentioned the two different populations that we have here. But I think just to redefine or to help myself answer this question really well, I think the two populations that we have are the clear bridge to transplant. They've been evaluated. They're on the list. Worsening progressive lung disease, that's pretty clear. ECMO is the answer for them. No problems. Mostly everyone agrees yes. And then you have those patients that come in who, just like we mentioned, hypoxemic, never seen a doctor before, don't know what their comorbidities are. And they're on ECMO with a bridge to question mark recovery, a bridge to nowhere, or a bridge to transplant. The way that I navigate this from day one is I try to be very explicit about three things. What does success look like? What does futility look like? And what is our exit strategy if we have one? And then we try to define what does futile care look like for this patient on ECMO. And I think it's ethically justified as a bridge if there's a realistic path to transplant and meaningful recovery. So we continuously reassess. Are the organs being preserved? Brains, kidney, liver. And so we get these tests, every day and do neurologic exams every day? Is the right ventricle still salvageable? And, you know, most of the time it is and need, like Jason mentioned, just VPA or something to help support them through that. The other thing that we ask, is the patient awake, interactive? Are they able to participate in rehab? Is the clinical trend improving? Are we taking big steps back? And if we are, what are the big steps that we're taking back? Is this irreversible injury that we need to start talking about? When the answer is trending towards a progressive multi-organ failure, refractory shock, or irreversible neurologic injury, because that happens often, that's when ECMO stops being a bridge and starts becoming a non-beneficial life support. And we have to name that honestly with the multidisciplinary team and with the patient and their family. And to bridge into that second is going to be transparency with families. And gosh, this is incredible. And I think that's going to be a big step forward. And I think it's incredibly difficult to do. For patients that are not actively listed, we don't have a relationship with them. They don't have a relationship with us. They don't even know how to spell ECMO. They don't know anything about ECMO and the complications that come with it. And so we try to frame ECMO as a time-limited trial, to be frank. So we say this is not a guarantee. This is a sliver of hope, and we're all going to cling to it and hope for the best, but prepare for the worst. And so we tell these families early on, we may reach a point where transplant is no longer safe or appropriate for you. And then again, the third thing is having an exit strategy. So before we initiate ECMO, or as soon as the patient is cannulated, we define what are the off-ramps. So what milestones would get them to transplant candidacy? We sometimes say the patients need to be walking a certain distance or their nutrition needs to be at a certain goal. So we define these for each patient. And most of these we're pretty rigid on. And then what would, prompt de-escalation or withdrawal look like? What is the maximum amount of time we can justify ECMO without meaningful progress? Because, you know, sometimes people are in ECMO and they have a week where they're depressed and they were previously walking a thousand feet and this week they went down to 300. And that doesn't necessarily mean we give up. We just say, okay, well, what does next week look like? So having these guardrails protects the patient from prolonged non-beneficial treatment, and it protects the patient from prolonged non-beneficial treatment. And it protects our team and all the teams taking care of the patient, in addition to their family from moral distress. And it ensures fair stewardship of ICU resources. So when the trajectory becomes uncertain, an ethical approach is structured uncertainty. So defined trial, measurable goals, which is so important for not only the patient, but for the ICU team, and then clear stopping rules. So what would futility look like? So transparency is always, always the plan.
Speaker 3It's fantastic. I mean, I think both the way you outline that is great. And as a framework, both for other healthcare providers involved in the decision and for families and for the patient, I think that's really, that's a great way to lay it out.
Speaker 2Yeah, that's, that's, that was great, Laura. And I, it's like, it's just, um, remind me, I, I've have very little real like transplant experience. Uh, you know, it's just some during fellowship and, and just, but, but, but even so being part of those discussions and feeling like you are holding people's lives in your hands, which we often experience. And the ICU, but it's just, it's, I think different. So many of the ICU patients we have are patients who we really never knew. We haven't established a relationship with them, you know, but then, uh, working in a transplant center, you can often have patients that come in and they end up on ECMO or, you know, other advanced therapies and their folks, you know, you've seen them in clinic for a long time. And now you're sort of like having to have these really hard discussions and make some really hard decisions. And I'm, I'm glad we have, you know, folks like you and Jason to do some of that. Cause my God, it's, it's certainly not an enviable task.
Speaker 1Yeah. The benefit we have, um, is, or at least the patients we get to see in our pre-transplant clinic, we do get the, um, opportunity to mention ECMO to them and complications of what ECMO would look like, et cetera. So most of our patients are somewhat prepared if, and when it comes to that.
Speaker 3I know Cyrus is going to want me to continue on with the case and move, move us along, but I just gotta, um, yeah, that's one sort of interesting question, which has come up at my center a few times, which is sometimes, somebody comes in, they don't have a pre-existing relationship. They're not listed for transplant anywhere. They develop severe respiratory failure requiring ECMO. And then it's almost like shopping around for a transplant center that will take them. Um, I'm curious if you guys have any thoughts on that, which is kind of interesting. I mean, we, we had a case at my hospital where we sent somebody, you know, thousands of miles to a, a transplant center that would while on ECMO transported them thousands of miles to a center where they did very well. And they've since come back, but you know, those are really challenging cases. And I'm, I'm curious if you guys have any thoughts on, on that, like what makes that successful?
Speaker 1Yeah. So I think, um, while this isn't a frequent occurrence, it definitely happens and it's definitely happened to us. And we'll probably again, we're all just in this to try to help the patient. And so if for some reason the patient, for some reason doesn't meet criteria at our institution for a transplant, we're going to look at other facilities to try to get them to come back. And so I think that's a really, really important part of this. And so I think that's, I think that's a really, really important part of this. And I think that's a really, really important part of this. Um, where they want to be. Um, sometimes it's something as silly as an insurance issue. You know, they're like not in our network, but they're in the hospital next door's network, which seems insane, but it happens. And so they were cannulated for ECMO at our institution, but unfortunately we can't start an evaluation because we don't have insurance authorization and send them somewhere else. So it can be as simple as that, or it can be that they're either really medically complex and need both a lung and a heart. And that's something that may not be done at a certain institution, and so they need to go elsewhere. So yeah, it can, it can happen. And we have no problems collaborating with other transplant centers to try to get the patient the best outcome. And if a lung transplant is what we think is the answer, then we're going to try to make it happen. Another really important point that I think maybe a lot of ICU providers or even pulmonologists may not know is most transplant centers require the patients to move to their center. So if you're an institution that can place someone on ECMO and needs to transfer them for a transplant evaluation because you don't have a transplant program at your center, it's really important to think about how that would affect the patients when you send them to, you know, X, Y, and Z transplant institutions because they're most likely going to have to move there. And it's such a financial burden for our patients to have to do that. And it's incredibly emotionally challenging to have to move to a new center for a year. So it's really important to think about how that would affect the patients when you send them to, you know, X, Y, and Z transplant institutions because they're most likely going to have to move there. So that's, I think, an important point that maybe not a lot of people know.
Speaker 2Yeah, that's a really good point. Jason, I wanted to throw you sort of like a nice and easy pitch here, something you could really like hammer out of the park. And that's really to turn to the intraoperative sort of considerations, intraoperative ECMO, cardiopulmonary support. So let's say we're now sort of in the OR. And of course, we're not an OR podcast, but I think it's helpful for surgical intensivists, let's say, to have an appreciation for what's going on. You know, behind the drape. So let's say, you know, we're in the transplant or we're sort of like about to approach it. Let's say we have the benefit of deciding, like this isn't a patient, let's say, on ECMO, but we're sort of trying to decide between ECMO or cardiopulmonary bypass or perhaps no extracorporeal support. What are sort of the ramifications of those decisions? How do you and the rest of the team tease through that decision in the best interest of the patient?
Speaker 4My preference is always to avoid using mechanical circular support if we can't. And there's similar to the initiation of ECMO, there's really three reasons that we do it whenever we get in the operating room. There's some cases that, you know, I'm going to have to decompress the heart and I'm going to have to support them with bypass or ECMO during this case. But for a lot of them, you figure that out once you get in there. But before I even make incision, I start nitric oxide to lower the PA pressures. I talk to anesthesiologists to optimize hemodynamics. And then we always start with the ECMO. And then we start with the ECMO. And then we just have a ventilation perfusion scan on these patients to know which lung is contributing more to their perfusion and ventilation compared to the other. And then we will try and do the other lung first. If they can't oxygenate well enough, ventilate well enough, or they're in heart failure, their PA pressures are rising, that's when we turn to ECMO or cardiopulmonary bypass. There are pros and cons of each. And I can talk about that a little more if that's helpful.
Speaker 3I want you to, but I want to ask you one other question first. In this whole episode, from the very beginning when I made it off Color Joke, we've been talking about a pair of organs, right? Maybe we should say a few words about single versus double lung transplant and how you choose their pros and cons.
Speaker 4Yep, absolutely. So that decision depends on the patient. And it also kind of depends on institutional practices. Single lung transplants are done way more commonly at some places than others. I think that has a lot to do with the patient population. But in general, if a patient can, if we expect them to do well with a bilateral lung transplant, then we give them a bilateral lung transplant. If we worry that they're going to be too frail to make it through that, then a single lung seems to be less than half the surgery and recovery of a double. You know, instead of having a very large incision, it's a much smaller thoracotomy through the side. It's less chance of bleeding. It's it's less hemodynamic disturbances during the procedure. So we generally reserve that for patients that are in their upper 60s or around 70 who are on the frailer side. That being said, there's some patients even at that age or who are frail who have a contraindication to doing a single lung transplant. The two main contraindications that would come to mind are infectious lung disease and worried about seeding the new allograft with infection or those with pulmonary hypertension that would overload the new lung that has less vascular resistance. Great points.
Speaker 3Yeah, back when I trained, there was this thing called cystic fibrosis that was a major cause of lung transplant. That's blessedly becoming less common these days.
Speaker 4Yeah, yes, it is big time. Absolutely amazing. Yeah, it is.
Speaker 1It's incredible. Yeah, we were talking about this earlier and like the UNOS data just came out and out of all the transplants that were done last year, it was like 14 or so were CF patients, which is completely insane. They used to lead the reason for needing a transplant, you know, and now they're almost not getting it.
Speaker 3Like a rounding error. Yeah, that's crazy. What progress? Okay, one more question I have to ask, which is kind of an interesting social question now. So one potential perk of doing single lung transplant is in a situation where lungs are a scarce and limiting resource. Does that mean that more people can get lung transplants? Are there any considerations there?
Speaker 4Yeah, yeah. That is certainly a consideration and it does work out that way at times. Whenever in the early days of lung transplant, the thought was that since the donor pool is so limited and single lung transplant is a good procedure that offers longevity, increased quality of life, that if we do single lung transplants, then we can double the donor pool. But in reality, only about a third of donor lungs, let's say only about a third of donors who have had a single lung procured, have the contralateral lung used for transplant in a new recipient. So it doesn't end up working out that way in practice. And the reason is that, you know, it's complex and multifactorial, but there's just not that many matches for a patient, for example, that's going to get only a right lung offer at this blood type, at this size. And then whenever you look at the wait list, there's just not that many people in the nation that meet that criteria. And then among those, you screen out transplant centers that can do it logistically, that may not like the organ offer, maybe there's pneumonia in that side. So it doesn't end up working out in a
Speaker 1one-to-one fashion. And the survival with a single lung is less than bilateral, five years compared to seven. That's right.
Speaker 2Okay. So getting back to kind of some of those considerations, I think we are going to talk a little bit about sort of pros cons of options, kind of intraoperatively ECMO versus preeclampsia. So let's get started. So can you speak to that, Jason?
Speaker 4Yeah. Yeah, absolutely. So both are widely used. Each has its own advantages and disadvantages. Most surgeons tend to pick one strategy and lean on that one pretty heavily and use the other one when there's a reason to do that or a reason not to use what they typically do. There's no difference in long-term outcomes among the two. And so it really comes down to practice patterns most of the time. There are some distinct advantages though with ECMO. The main thing that comes to mind is that you don't have to anticoagulate to the degree that you do for cardiopulmonary bypass. So for ECMO, we're generally running ACTs above 180 compared to 480 on cardiopulmonary bypass. That's the difference of 5,000 IV heparin versus 30,000 IV heparin depending on the patient. And I've heard of some places not even giving heparin and the outcomes are good. Because of that, lung transplants on ECMO tend to have shorter operative times. They have reduced requirements for blood transfusions whenever you look at large patient databases. But there's some distinct drawbacks. ECMO doesn't have a reservoir. The patient is the reservoir. Blood comes in, it goes through the oxygenator, it goes through the pump, it goes back to the patient. With bypass, we can completely empty out the heart. We can recapture our blood loss in the operative field and we can put that back into the patient. That's the main difference in my mind. The reason I prefer to do bypass on most patients is because it just gives you more control. And then also with ECMO, because there's no reservoir, there's no tolerance for air. So if, God forbid, a cannula slips out or there's some issue with the circuit, that could result in a really catastrophic problem and air embolism. With bypass, that's not a problem at all.
Speaker 2Great answer. And it's, yeah, I was saying it before. So the surgeon's leaning into control. That's hard to believe. It makes sense. Makes good sense. Touche. Same though. Same though. Cool. Okay. Well, I think that's, yeah, that's a great little overview.
Speaker 3Nick, sorry. So let's go back to our hypothetical patient here. Yeah. So let's say that they've undergone surgery and things went well in the operating room. But now fast forward to the first day post-op, they're now developing worsening hypoxemia. Laura, how do you differentiate common things we see, like infection and volume overload, from more transplant-specific things like rejection, primary graft dysfunction? And what are we supposed to do with this when we see this?
Speaker 1Yeah. So early on, within the first couple of days after a transplant, if they have bilateral infiltrates, they're not going to be able to do anything. So they're not going to be able to do anything. Yeah. So early on, within the first couple of days after a transplant, if they have bilateral infiltrates, PF ratios that aren't looking good, it's almost always going to be PGD. I say that, but PGD is supposed to be a diagnosis of exclusion. So technically, you're supposed to exclude everything out, everything else out, and then say, okay, I don't have an infection. I don't have volume overload. I don't have rejection. So it's PGD. But that's not how it works in the real world. So what I would say is we do a bronchoscopy on all of our patients immediately after the transplant. And almost all of them grow something on their BAL. So almost every single patient immediately after transplant is going to have some sort of infection or positive culture in their BAL. So I don't know if it's that easy to differentiate infection from PGD. And almost all of them are going to have some sort of volume overload. They get 15, 20 liters or so, depending on how well our surgeons perform. Just kidding. A lot of volume early on. I was trying to dig over at Jason, and he just ignored me, which is pretty typical. For the people who are
Speaker 3watching this on YouTube, there was a great look there. For people who are listening, you'll just have to take my word for it. But it was a great
Speaker 4surgical look. Look, we've had some hard transplants lately, okay?
Speaker 1Laura? No, we haven't. They're all doing fabulous. Despite the 20 plus liters you give them. No, but in all seriousness. So PGD comes as a diagnosis of exclusion. It has certain criteria that we use. We measured on post-op day 0, 24, 48, and 72. And then everything else kind of comes along with it. Everyone gets a ton of volume. Everyone has a positive BAL. Almost 0% of patients are going to have hyperacute rejection because we do such a great job matching them pre-transplant. So we don't really see that often anymore. At least not as much as we used to. At our institution, we have like zero episodes of hyperacute rejection. So not a thing for us. At least within the first 72 hours, you can definitely get rejection after that. But again, what's interesting to know about PGD is that it is a non-cardiogenic pulmonary edema pathophysiology. So it's very similar to ARDS and almost like the ARDS of a lung transplant patient. In fact, if you look at it under a slide, it's going to have diffuse alveolar damage, just like ARDS does. You know, so that's the way that I think about PGD. Early on, usually some sort of DAD-like histology. And then the criteria are pretty much the same. The PF ratios differ a little bit when you want to grade it. And then again, the big etiology that contributes to it is an ischemic reperfusion injury. So there's increased permeability across the alveolar capillary membrane. You have impaired sodium fluid transport. And then there's increased permeability across the lymphatic drainage is not immediately restored after implantation. And so the lung early on simply cannot tolerate the amount of volume that it sees. So sometimes we get patients with pulmonary edema.
Speaker 2I just couldn't help but look over at Jason when you're talking about sodium and other, and he was just like glazed over for a hot second, like smirking a little bit. I was like, oh man.
Speaker 1As he passed out in his chair, maybe I need to shut up and we can move on. No, no, I'm into it.
Speaker 4You surprised me with the lymphatics thing. That's a really good, that's a really cool point. I haven't, I don't know that I've thought about it quite that way, but you're right. The lymphatics are cut on all these transplants. And it takes about six to eight weeks, at least in mice to regenerate them. So that very well could explain why they, you know, don't, don't have a good capacity to handle fluid shifts.
Speaker 1I think about lymphatics every day.
Speaker 4Just wake up and think of lymphatics.
Speaker 1Yeah. I wonder what the lymphs are doing.
Speaker 2Maybe, let's look at the, Let's turn the coin over, Jason, and talk about some of the early post-op complications related to the surgery itself. So maybe you can help me and our listeners understand what are some of the red flags for surgical complications, things like bronchial and asthmatic dehiscence, vascular bleeding, and how can we as bedside intensivists avoid missing those complications?
Speaker 4Yeah, absolutely. Those are certainly things that I'll speak to, but I just want to say and lead with that 95% of my attention immediately after transplant is going to medical issues. It's going to hemodynamics. It's going to making sure that the patient is doing well clinically because that's where most of the pitfalls are. There certainly are surgical complications, and these are things that we got to keep a lookout for, but they tend to be pretty rare. It's like bleeding is the most common by far because these are major operations on big blood vessels. But not everybody's risk is created equal. We've done some lung transplants recently that were completely fused from prior infections. Those are really long surgeries. Those have a much higher risk of bleeding. Patients that have not had prior chest surgery, have not had a pleurodesis, have not had recurrent lung infections, those tend to be much faster, not get blood transfusions or just have some product given, and have a lower risk of bleeding. The chances that you're going to actually have to go back to the operating room for bleeding is pretty low. It's probably about 4% or 5%, maybe 1% and 20%, but it's always something to look out
Speaker 3for. And just to double-click on something you said there, Jason, so I think a lot of people might naively think that it's the anastomosis that's going to bleed. You're sewing these pulmonary arteries and pulmonary veins together, but that's not the case. Is that right?
Speaker 4Yeah, yeah. It's pretty unusual. It definitely can happen, especially whenever patients have. been on very high-dose steroids, their tissues get to be very, very friable, and if they have some sudden increase in their PA pressures, heart failure, but for any reasons, hypoxic pulmonary vasoconstriction, something suddenly increases the pulmonary vascular resistance, theoretically, that could cause a bleed from the anastomosis. That being said, I haven't seen it. Most of the bleeds are usually from the bronchial arteries. We have to cut all the bronchial arteries when some can be quite sizable, especially in patients that have chronic inflammatory phenotypes, and then the intercostal branches from the intercostal arteries. Those tend to be the most common reason, or the internal mammary, chest wall, basically.
Speaker 3Great. Okay, so that's bleeding, and now let's talk about the other anastomosis, which is the airway anastomosis. What are some issues that can arise there?
Speaker 4Yeah. So issues with the bronchial anastomosis are pretty uncommon immediately post-op. They certainly can become a problem in the next. In the next couple months, but in the immediate peri-op setting, it's usually okay. You know, the patient gets good connections, things are going to heal, they're airtight, it's all good. But by the nature of a transplant, the lungs connection is ischemic, because you have to cut the bronchial artery circulation in the donor and the recipient. So when you put the two together, the donor bronchus at the anastomosis is going to be ischemic. And so because of that, a lot of patients, I'd probably say the majority, get some sort of mucosal sloughing at the anastomosis from ischemic airways, but that's rarely clinically significant. And whenever you look at, you know, what we really care about is clinically significant airway ischemia, that's single-digit percentages that have that. We're talking like 2% to 8% in the literature. Most all of these can be managed bronchoscopically with debridement, stents. Occasionally, that sloughing mucosa can develop infections, namely fungal infections, and that's what we're looking for in these patients, and these patients need inhaled antifungals. Reoperation is very rare. I have heard of it where the anastomosis needed to be revised, but that's a pretty uncommon thing. And the risk factors for the connections of the airways having problems are pretty generalizable risk factors. A long ICU stay, older patients, patients that have been on a lot of steroids, have diabetes, things like that. And these are usually detectable. They're usually detected during routine surveillance bronchoscopies. But if it were to present early, it would present as a new pneumothorax or a large air leak, probably not a small, subtle one, a large air leak in a chest tube that previously didn't have one. That should raise your suspicion for it. Great point. Yeah, for bronchodehiscence.
Speaker 3One other point that I often make to people is to be very mindful when intubating somebody who's a lung transplant recipient. Just because theoretically, or maybe not theoretically, an endotracheal tube that's placed too deep could damage the anastomosis.
Speaker 4Absolutely, yeah. But because of the airways anatomy, that right bronchial connection is very close to the carina, and then the left mainstem is much longer. And so that tends to be what we see when there's iatrogenic airway injuries, either from a tracheostomy being placed in a post-patient, that's another cause, or when the ET tube is too deep, it tends to be intubated. An injury to the inferior right bronchial anastomosis.
Speaker 1Yeah, and it happens. We've seen it before.
Speaker 3It happens. Yeah, I think the takeaway is get that tube just through the cords. Don't go too deep. That's right. Or potentially, you know, intubate over a bronchoscope if you're really worried, because then you can see where you're going, and you can evaluate the anastomosis at the same time. Okay, well, this is an excellent summary of the sort of immediate post-transplant complications and issues. Let's think now about kind of. that trade-off that we talked about earlier, the trade-off between infection and immune suppression. How do we balance the risks and benefits of these different meds? Laura, if you want to tell us more about that.
Speaker 1Yeah, so I think we talked about the immunosuppression early on, but what I'll say is most programs have fairly structured protocols that they follow for induction therapy and maintenance therapy, immediately post-operative. And then, you know, we do for years and years, but sometimes that management alters. I will say. I will say there are a few times where we will deliberately change the immunosuppression because we think that the patients may not tolerate a standard therapy. For example, some of our patients who come to us with ILD because of short telomere syndrome, we know that they have bone marrow suppression or at least increased risk for bone marrow suppression. So either after transplant or for, you know, immediately after transplant or further after transplant, we may have to remove cell sept or mycophenolate because it can cause, you know, endometriosis and neutropenia as well. So we do.
Speaker 3That's a board question, folks, by the way, short telomere syndrome and sensitivity to
Speaker 1MMS. Yes. Yeah, it is. But we see it all the time. It's real. And in our patients, we get a lot of ILDers who come to us with short telomere syndrome and it happens. Another board question, just FYI, is the bronchial anastomosis and mold. Mold love bronchial anastomosis. So if you see dehiscence, it's almost always caused by mold. Sometimes pseudomonas, but almost always mold. Anyway, getting back. The question at hand, because we worry about infection, especially donor-derived infection within the first couple of weeks, we have standard antibiotics that we put our patients on for the first three days. We cover MRSA with vancomycin. And in the first 10 days, we cover our patients with cefepime. And that's just based on our antimicrobials history. And then if the donor has grown something different, we may change our antibiotics to try to tailor to that. But almost always, that's what we start with. And then we also initiate antifungal therapy, prophylaxis or therapy if the patient needs it early on. So we try to broadly cover anything that could come from the donor or could arise because of a nosocomial infection early on after transplant. And then we always keep a low threshold in case they develop some sort of sign of new infection so that we can treat it as soon as possible. And then renal injury. There's always a concern with tacrolimus. It's notorious for causing both AKI. So you may see that early on post-transplant and CKD long-term. So both issues arise. And then I don't know if this is well-known, but both cyclosporine and tacrolimus are known to cause thrombotic microangiopathy. So like TTP and HUS do happen. And we've seen it before when tacrolimus and cyclosporine are on. And I'm like incredibly boring to Jason. So I'm going to try to speed this up.
Speaker 4This is great. I'm learning. You tripped me up with TTP. I had to think about that one. And I'm still not sure I got it right.
Speaker 1Okay. Well, we'll talk later. So what's interesting about AKI early on with tacrolimus is that it's almost like a pre-renal process. So the pathophysiology there is that it causes afferent arteriolar vasoconstriction. And so, you know, we try to avoid this as much as possible, but sometimes it happens and we just ride through it and things get better and we target a level of 10 to 15. And if they're starting to get an AKI, we may go down a little bit lower to 10. So chronic injury happens later from tubular damage. And then you see things like diabetes hypertension, which contribute to it as well. So to answer your question in a very long-winded way, there's just a bunch of balancing that we try to do with pretty aggressive immunosuppression up front and the side effects that happen. And as the side effects come along, we just treat them as they happen.
Speaker 3one point that I always make to people, you know, caring for transplant patients is BID and Q12 aren't the same thing. And, or it may not be at your institution. And this is a really important point when it comes to tacrolimus. Do you want to say anything about that?
Speaker 1Yeah. So, you know, when you say that, I think about all the patients who are like, look, I'm not a morning person. I wake up at 10 a.m. I'm not going to wake up at 6 a.m. or 8 a.m. or whatever you want me to do to take my tacrolimus. And so the way that we dose it in the hospital is 8 a.m., 8 p.m. And then we get a trough at 6 a.m. Any deviation from that is not a true trough. And we don't really know how to manage the tacrolimus if it's not a true trough. You just kind of shrug your shoulders and move about your day. And then the one important thing to know about rapamycin is that we don't get labs every day to check the levels. We only check the levels about every five to seven days because it takes such a long time to get up to a steady state. So if you check a trough earlier than that, it's probably not going to be reflective of a true trough. So, yeah, you know, we do 8 a.m., 8 p.m. religiously. Our patients who go home try to do that. But we do have a patient who's like, yeah, no, I'm not waking up at 8 a.m. So when they come into clinic, we have to know what time to get their labs so that we do have a true trough.
Speaker 2So, yeah, all super helpful, especially that point on the timing of the tacrolimus. And when to keep an eye on it, when to be checking the trough, how to counsel the patients. I think that's super important. I wanted to move to another kind of question that comes up often. And certainly, you know, Laura, whatever your insights are here would be helpful. And then Jason, too, if you have any thoughts. But let's say that this patient now developed some new infiltrates. And then let's say they've left the ICU. And so you actually you hear about them feeling not so great on the outside. So get an X-ray. You see some new infiltrates. And then you get some spirometry on them. And it looks like their lung function is actually going to be doing a little bit worse. And so in that person who's having a change on their imaging and maybe a little bit of a functional change that you wouldn't expect, how would you approach the differential on that? And when would you treat empirically for rejection in a patient like that?
Speaker 1Yeah. So if they're early post-transplant, almost always it's going to be infection. The thing about rejection is more often than not, it's silent, right? So like they come into clinic, they're actually feeling great. And we get PFTs and they've dropped from their baseline. And then we get a bronchoscopy. And they have like A3 ACR, which is a high grade and it's terrible and scary. And their X-ray is completely clean. So always we have a low index of suspicion for rejection. But if it's early on, they just left the hospital, they have multifocal opacities, and it's less than a month from their transplant, I'm really worried about some sort of nosocomial infection that they left the hospital with that was brewing. And now it's really raging and ugly head outpatient. If it's like six months later, we're going to have a new patient. And then we're going to have a new patient. is highest on my differential. And I'd be worried about that and be getting a bronchoscopy immediately. But I think what most of us would do is, if we see this patient in clinic, we're going to directly admit them, start them on really broad spectrum IV antibiotics to try to treat some sort of infection. And we get a bronchoscopy with BAL and transbronchial biopsy, or we do a bronchoscopy with BAL and transbronchial biopsy ASAP to try to rule out at least acute cellular rejection or rule in acute cellular rejection, and then see what's going on on their BAL, what type of infection do they have. So we'll send bacterial, we'll send fungal and AFB cultures. We'll send CMV, PCR, aspergillus galactam and I mean, you know, pretty much the whole gamut of things. Some centers send to Karius, which is, you know, like, I'm sure you guys have heard of this. It's, yeah, okay. But why don't you tell
Speaker 3our listeners though, it's a great test.
Speaker 1Yeah. So, you know, Karius is a test that will give you like, what, 101 results of different types of infections. It's a PCR and is great in terms of pretty quick turnaround. And the problem with it is that sometimes it will give you results that you don't know what to do with. So it seems to be really, really sensitive and picking up a lot of different organisms that sometimes you don't know what to make of. But some centers do use it and they treat everything that grows and their patients do really well. So I think there's something to be said about it. The problem is that it's incredibly expensive. And so we don't regularly use it at our institution. And so, you know, you wait a couple of days for the results. In the meantime, we're getting some serology. We can check something called donor-derived cell-free DNA. Um, which is a new hot thing. And I really shouldn't say new hot thing. I mean, my gosh, it's been out in the market for ages now, but it helps us rule in or rule out, I should say rejection and prospect or donor-derived cell-free DNA is a talk on its own. Um, but sometimes we get that. And then of course we're checking serology to see if the patients had developed, um, donor specific antibodies to rule in or rule out antibody mediated rejection. So we do like a when these patients are this sick, decline in PFTs, they don't feel good and their spirometry is down. That's really concerning.
Speaker 3Yeah. I think, I think that's the key takeaway for people who don't, who don't take care of transplant patients frequently, which is that there's no such thing as a little drop in lung function in these folks. We have to treat it very seriously because it can portend something really serious, either an infection or rejection.
Speaker 1Yeah. Yeah, absolutely.
Speaker 3Turning to kind of the, the infectious side of that. Um, what infections are you worried about in these folks? You mentioned a couple, but maybe we could run through a little more detail.
Speaker 1Yeah. So timing is the most important when we're trying to figure out what type of infections are brewing. One month after a transplant almost always are going to be some sort of nosocomial bacterial type of infection. So Pseudomonas, MRSAs, um, we see Acinetobacter, um, donor derived are usually early on, but can pop up later on our cultures. So, sometimes we're surprised and we get an M. abscessus, you know, cause these patients or the donors do aspirate when they have their event and we transmit that to our recipients. So we do see NTM's early on. Molds are huge. We see Aspergillus frequently. So those are the common things within the first month, at least within the lungs. And other common things would be like C. diff, Lyme infections, those types of infections, um, as well. And then you have the one to six month period where that, uh, pneumocystis starts to rise and the viruses, CMV, um, EBV, those types of viruses can cause problems. Um, but pneumocystis is a big one. So that's why we prophylax, um, all of our patients for pneumocystis pneumonia, and we prophylax all of our patients for CMV, at least until they get to one year. And then we may stop it at one year, depending on their risk, their donor recipient match. So I would say if I was seeing this patient in clinic and I'm on that's what I would be thinking about six months, it's going to be some sort of virus fungus to pneumocystis. And then further out, it's also going to be other types of, um, like flu bacterial infections, your run of the mill community acquired pneumonia, those types of things. And viruses can cause problems. Um, especially if you have a patient who's had recurrent rejection and you're giving them a lot of immunosuppression, they're set up for a virus to give them problems in the future.
Speaker 3Uh, you know, I, I don't love, I don't love this saying, but you know, people can have fleas and lice. And so often, you know, these things, you know, one can cause the other, or people are set up for more than one thing. So like a viral infection can cause rejection or somebody can have multiple different infections at once. Jason, do you
Speaker 2guys ever have to get involved in the diagnostic process here with these types of infections from a surgical standpoint, or is it usually just bronchoscopic
Speaker 4stuff? Yeah. The vast majority of is bronchoscopically the times that we have to intervene surgically is mostly with, you know, a virus. So, you know, if you have a virus that's in you know, nine times out of 10, maybe more than that. It's whenever there's a plural space infection, the majority of them are just treated medically.
Speaker 2Makes sense. Yeah.
Speaker 1Jason's getting involved. We have problems.
Speaker 2Yeah. I would, I would imagine so. I would imagine so. So kind of, as we start to wind down our conversation, we've been on the, on the line now for a little while here, and I want to make sure that, you know, we respect everyone's time. I did want to at least spend a moment here talking about clad or chronic long allograft dysfunction. And, and, and ask you, you know, really both of you, maybe, maybe again, Laura first, because I know this is a little more on the medical side of the house. So for intensivists, I think clad can often feel like more of a distant outpatient problem, but I'll ask you, you know, what early ICU relevant events can increase the long-term risk of a patient developing clad and what can we do differently?
Speaker 1Yeah. So thank you so much for this question. Anyone who thinks about distant outpatient problems knows the way to my heart because this is what I do. This is my bread and butter. And the earlier we think about it, It's not so distant for you
Speaker 3because you see these patients in clinic.
Speaker 1So I, you like, this makes me want to cry tears of happiness that you mentioned this. I appreciate the question so much. So I don't think intensivists always realize how predictive the early post operative ICU course can affect our long-term outcomes. I mean, I like to list a few PGD, PGD, PGD, right? Like PGD over and over again is a, is associated with long-term chronic rejection, which we call clad. And it's specifically PGD grade three, one and two, maybe not so much, but definitely three can, um, is associated with clad and increased, um, at least 90 day mortality and probably just mortality in general. general. So prevention.
Speaker 3Just for our listeners, the grading is based on P to F. You don't have to worry about what the numbers are, but just so you know, just like everything, we grade everything in medicine, right?
Speaker 1Yes. Yes. Grade is P to F. You got it. And always prevention here matters. And we do our best to try to prevent, but I think the most important thing in addition to that is early recognition and aggressive supportive therapy. That includes ECMO when appropriate rather than prolonged interest ventilation. This is where I care about ventilator-associated injury. Not pre, but post. Not pre, definitely post. Please don't hurt the lungs. Something that we don't appreciate very often and something that Jason mentioned earlier is foregut dysfunction. So a lot of our patients come to us with some sort of esophageal gastric motility issue, and we can't fix that. The issue pre-transplant because they may be too sick or, you know, something. They can't get it done before the transplant. And so they actually get the transplant and will still have the foregut motility issue after the transplant with the goal of treating it in three days. But it's really important that we feed the jejunum and not the stomach if patients have really good, really terrible foregut issues. So sometimes you'll see us putting in GJ tubes, instead of just G tubes, if our patients have known foregut motility issues. And sometimes, you know, we don't do it very often, but if we do do it, it's to a bridge to some sort of surgery to fix whatever the issue is. And that is because aspiration esophageal dysmotility, really bad gastroparesis, are associated with CLAD. So that's something that we pay attention to, something that we always talk about on rounds and focus on. So we try to get, if they have a dop hop or feeding tubes, we try to get it post-transplant. We try to get it post-pyloric as much as we can. And then I know this sounds silly, but DVT prevention is another big one. DVTs are notorious for our patients because of the nature of the surgery and the nature of their lung disease and their inflammatory and their clotting and their thrombocytopenic. And so a lot of our patients develop DVTs at some point during their postoperative stay. And this is associated with worse, of course, morbidity, but mortality most importantly. So we try our best to prevent DVTs by removing lines as quickly as possible, starting DVT prophylaxis as soon as it's safe. But really mobility is key here too. And then kidney injury is huge. I talked about that earlier with tacrolimus and the AKI. We try our best to avoid any nephrotoxins. We wait a couple of days before we add Lasix. We don't aggressively go up on our tacrolimus goal, but anyone, who develops CRT and eventually needs intermittent hemodialysis after transplant has increased morbidity and mortality after transplant. So we try our best to optimize those patients and prevent kidney injury as much as we can. And then something really important is blood products. So blood transfusions, specifically platelet transfusions, are sensitizing events. So if you have a patient who is crashing on the floor and they're sanguinating in front of you and you're like, well, I really don't think I should give them this crash blood because they may have a sensitizing event, like I appreciate you thinking about me and the patient's future cloud, you should probably still give them the blood transfusion, but it increases their risk for AMR and rejection in the future. And so we really try to hold off on those types of transfusions if we can. And then the last thing is virus prevention. Any sort of rhinovirus, influenza, COVID, you know, whatever it may be. Given to these patients can cause problems in the future and increases their risk of developing chronic rejection. So even just your run-of-the-mill cold can cause really big problems for these patients in the future. So we try to always wear masks when we see the patients. If we're not feeling well, we stay away from them. Prevention here is key.
Speaker 3Great points. Yeah. So, I mean, what I'm taking away from this is that it's just like everything in the ICU. It's not about doing one big thing. It's about doing a hundred little things all right. Right. You know, it's about avoiding all of these death by a thousand cuts that can set people up for bad outcomes in future years. Right. Yeah. So, so thinking about that now, thinking about kind of, you know, the months and years that follow, maybe we should talk a little bit about prognosis. I know you said earlier kind of what the, what the typical survival is after lung transplant. Maybe you could speak to that a little bit more. And then what, what do you do, you know, if you're, if you're at, you know, let's say year eight or nine and their lung function has steadily declined, like how do you approach that situation?
Speaker 1Yeah. You know, the situations where patients develop chronic rejection or even acute rejection and all of a sudden have AMR or ACR that lands them in the ICU on a mechanical ventilator, talking about tracheostomy, talking about end of life, these situations happen more often than, than not. And so we unfortunately have a lot of experience with them and these situations are so difficult. And so I think it's really important to think about that. And I think it's important to think about that. And I think it's really important to think about that. And I think it's really important to think about because these patients are our family. We know about their goals, their lives, their grandchildren, their travels. And you know, the name of their parent. And I do. Right. Hopefully they've gotten rid of, but occasionally they don't, but like, they're so difficult. Like we, I've cried in patients rooms before when we have these conversations, they are incredibly difficult, but they, they know that it's coming. And, and we're at some point in time where we're like, we're at some point and we're realistic with them and talk about expectations and how things are going to look for the future. We are incredibly lucky at our institution because we have a palliative care provider who sees our patients with us and sees them pre-transplant, early post-transplant and then specifically follows our patients with chronic rejection. And she has changed the landscape for these patients because they know her really well. And, and when we have to start focusing our goals of care on palliative symptoms more than I want to live forever, she is wonderful at helping us tackle these discussions. And so we're really lucky in that sense, but yeah, I mean, we have in our pre-transplant clinic, we have conversations with patients about like, this is the average survival for a single. This is the average survival for a double. We explain the process. So everyone goes into this knowing that it's going to happen at some point. And yeah, it's kind of a well-oiled machine. Jason, I wanted to give
Speaker 2you an opportunity to chime in as well from like a surgical perspective when you're sort of going into the journey with the patient, if there's anything you say upfront to sort of prepare them for a possible bad outcome and how you kind of have that discussion.
Speaker 4Yeah. Yeah. I mean, it's, it's really important for me to understand that, that they know can really deeply on a deep level, what this process is, what it looks like, what the recovery looks like, what the risks are, and then the good that, that can come from it. You know, I, everybody wants to live longer, live better. But, but it, it always gets harder before it gets better for these folks. And, and so whenever I see a patient in the pre-evaluation phase, I booked that clinic visit for an hour and we go through this fully and we have lots of time to talk about these things and meet with the family because whenever we make place them on the wait list, us, the patients and their family, we're all in, and we're all in one mind and one accord. And, and that just, it takes time and it, and it really takes a lot of, a lot of listening and, and, and the space for that discussion to happen.
Speaker 2Well, folks, thank you for joining us for this episode of Critical Care Time. We had a fantastic discussion with Laura and Jason where we, I think, really drilled down pretty deeply into the world of lung transplant with a focus on, on considerations for the intensivist. But then I think we also did a nice job of talking about some of the considerations, kind of pre and post transplant and, and really a nice little tasting menu, if you will, of all things related to lung transplant. I hope you guys enjoyed it. If you want to learn more, you should definitely check out the website. You should do a fellowship
Speaker 3in this, actually, if you want to learn more.
Speaker 2That's right. Do a fellowship.
Speaker 1Or just come hang out with us.
Speaker 2That's true too. Or what might be a little faster is head over to www.criticalcaretime.com Check out our show notes, subscribe to our mailing list, leave a comment. Again, thank you, thank you, thank you to our phenomenal guests. You guys were amazing. Thank you so much.
Speaker 3Hey, it was a pleasure. Thank you. It was fun. Also, big thanks to our listeners, especially those who have left us five-star reviews. We really appreciate you. And that one person with the one-star review, we do not appreciate you, but most of you, five stars, we like you. Big thanks to our team over at PodPaste. They're the production team that, you know, makes this show possible. Kurt Belknap for our theme music, everybody else behind the scenes who contributes. Thank you all for supporting us. If you haven't already, be sure to subscribe, give us a like, give us a five-star rating. Yeah, we appreciate all of you.
Speaker 2And after you've left that five-star rating, give us a holler. We're on X as at CritCareTime. We're individually at NickMMark, at Askins underscore Razor. You can follow us on Instagram, LinkedIn, Blue Sky Threads, YouTube, or really some permutation of Critical Care Time will find us.
Speaker 3Right. We especially love LinkedIn, our favorite social network. And now some disclaimers. The views expressed within this podcast and any associated media do not necessarily. necessarily reflect the views of our employers. All references to patients or encounters have been modified to be HIPAA compliant, and thus any similarities to real-world cases are purely
Speaker 2coincidental. And remember, this podcast is for educational and entertainment purposes only and should not be used in lieu of seeking medical advice. One final thank you to our amazing guests, to Laura and to Jason. You guys are awesome. I'm Dr. Cyrus Askin. Thanks for listening. And I'm Dr. Nate Mark. I'll see you next time. Bye.
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