Good afternoon, everybody. So as you heard from the previous two speakers, bridging these patients, these really sick patients, to transplant is of paramount importance to make a impact on their survival. So I'll focus on peritransplant and post-transplant ICU management. These are my disclosures. So from an outline standpoint, I'll briefly recap on some of the thoughts of the previous speaker about reviewing the pre-transplant arrangements in deconstitutory cirrhosis and ACLF that specifically influence post-transplant care. And then we'll just briefly recap on an organ system-based review of management strategies for all the organ systems, again, thinking about how do you bridge these really sick patients to successful liver transplantation. And then I want to switch gears and talk about sort of newer strategies as to how we're thinking about increasing the organ supply for liver transplant. And specifically, I think a lot of you may know, there has been an explosion of utilization of DCD organs, donation after cardiac death. So we'll briefly touch on that. And then I want to move on to, in the post-transplant phase, once the patient is transplanted, what are the specific organ-specific strategies to make sure that the patient has a stable post-operative course and a successful course? And then I'll wrap it up with thinking about specific surgical complications. Some of you in the audience may be taking care of these patients. So what are the specific surgical complications that we deal with, hopefully not often, in this patient population? So moving on to pre-transplant derangements, I think just to recap on the previous speakers, you're dealing with a patient phenotype that can get very sick very fast from a multi-organ standpoint. So if you heard about septic and hepatic encephalopathy from a neurologic standpoint, there's septic and cirrhotic cardiomyopathy. From a lung standpoint, unique derangements such as acute lung injury and hepatic out of thorax. From a cardiovascular standpoint, as you heard from Dr. Dong about a decrease in their baseline mean arterial pressure, that sets them up for distributed shock. From a renal standpoint, you heard eloquently from Jodi about HRS-AKI physiology. And then you have the direct complications of variceal bleeding, tense societies, abdominal compartment syndrome. And then to top that off, you have coagulopathy, a metabolic acidosis, and then I think an important take-home point from an ID standpoint is these patients are immunocompromised, exquisitely sensitive to multiple infections. So the goal, as you think about transplantation, is somehow you stabilize this really complex phenotype, get them to successfully maintain the window of transplantability from a physiologic standpoint, get them to liver transplant. And as I think a lot of you know, there can be a tremendous reversal of multi-organ failure once the new liver goes in, not just hepatic, but extra hepatic resolution of organ failures. The important take-home message for me in this slide is that the one thing that I think about in the post-transplant phase is keep an eye on your pre-transplant derangements that can influence post-transplant management. For example, if you have a large hepatic out of thorax, that is gonna come back post-transplant because you have diaphragmatic defects. If you have bad HRSAKI, you will be seeing AKI post-transplant. So how do you think about that? How do you anticipate that problem post-transplant? So just to recap again, and I'm just repeating some of what Dr. Dong said, but just to recap sort of the summary. Again, how do we think about bridging different organs for stabilization for transplant? From a neurologic standpoint, you heard about stabilizing hepatic and septic encephalopathy. We use albumin dialysis at our center for stabilization of refractory hepatic encephalopathy. From a cardiovascular standpoint, it's important to anticipate the risk of distributed shock in these patients because of their low mean natural pressure. And the other unique thing is monitoring for abdominal compartment syndrome physiology because of tense societies. And then you heard about the empiric use of stress-to-steroids for refractory shock. From a lung standpoint, anticipating that they can develop diffused lung injury and ARDS physiology given their immunocompromised state. And the other unique thing that we do at some frequency is drainage of refractory hepatic hydrothorax with small bowel catheters as a bridge to urgent transplantation. And then from a renal standpoint, you heard eloquently from the previous two speakers about anticipating and treating AKI aggressively, including preoperative CRT and continuation of intraoperative CRT in these settings. So again, I repeat this to sort of highlight the complexity of these patients and the importance of supportive care to maintain the physiologic stability of these patients as we try to keep them in the window for life-saving liver transplantation. So this then begs the question, when is a patient too sick to transplant? And the practices are all over the place. In North America and in Europe. And these are really center-specific. How much pressure is too much pressure? How much lung injury and FIO2 and PEEP is too much? And that becomes a center-specific practice depending on the transplant center. But a few sort of common themes may be from a neurologic standpoint, if you have refractory severe HE, is that a problem? You just can't wake the patient up. From a cardiovascular standpoint, it's a bit of a moving target, but is an RIP equivalent of 0.2 micrograms per kg per minute too much? So that's a conversation. From a lung standpoint, your FIO2 and your PEEP requirements, how much is too much? And this is the rule, for example, that we use at our center with respect to a potential pulmonary contraindication. From an ID standpoint, if they have active bacteremia or fungemia, that becomes a deal breaker with respect to thinking about acute transplantation. From a cardiovascular standpoint, as you heard, there's a unique form of pulmonary arterial hypertension these patients can develop, and moderate to severe portal pulmonary hypertension defined as a mean PA pressure greater than 35 would be a barrier in most centers. So this is just to give you an idea of some of these barriers that can become a problem as we think about transplanting these patients. All right, now let me switch gears and talk about strategies to increase organ donors. And just to take a deeper dive here, I think a lot of you know hepatitis C is becoming a thing of the past because you have such good drugs to eliminate hepatitis C. And so in the DA era, there is increasing utilization of hepatitis C positive donors into hepatitis C negative recipients. So at our center, for example, everybody gets offered a hepatitis C positive organ irrespective of their status with respect to hepatitis C. They have to opt out of it because we know with much certainty that we can eliminate hepatitis C with two months of therapy when it recurs post transplant in the hepatitis C negative recipient. And just to give you an idea of some of the data, this is a publication from one of the hepatology journals that over the years, you can see that there's a step up in hepatitis C positive donors across the board, even in hepatitis C negative recipients. And on the right, and hope you can see that on this slide, but what I wanna draw your attention to is the last row. And the last row is hepatitis C positive donors into hepatitis C negative recipients. And as you can see, this is data till 2019. But, and this data is looking even, this pattern is maintained as we look into 2025, this has become routine standard of care that hepatitis C positive donors are routinely being transplanted to hepatitis C negative recipients. So this is one major strategy that has sort of changed the paradigm with respect to increase the organ donor supply. The other thing that just to sort of, in the ID standpoint, this became important in the COVID era, we were transplanting COVID positive donors into COVID negative recipients except lung transplantation without any recipient antiviral prophylaxis. So this was one of those, another examples from an ID standpoint that we try to increase organ supply. And then the third thing, just to give you an example is HIV, the utilization of HIV positive donors. We, many centers are routinely transplanting hepatitis C positive donors into HIV positive recipients. So that's become almost standard of care. Moving on to I think another important point, a lot of you may be familiar with this, but this is a massive increase in DCD donor utilization, donation after cardiac death. So the conventional approach was to use donation after brain death. And there were some concerns about using donation after cardiac death donors because of the increased risk of ischemical angiopathy because of a higher rate or higher duration of lack of blood flow. But what has dramatically changed is the use of machine perfusion. You're basically taking the organ out from a DCD donor and putting it straight on a machine perfusion that maintains organ perfusion as you bridge that donor to a liver transplantation. And so this has really changed the paradigm with respect to using normal thermic machine perfusion in an ex vivo setting. The organ comes out, goes straight on a pump, and that organ that previously was not deemed usable has now become usable across the world, if you will. So just to give you an idea of some of the data, this is data from the US. And again, you can see the time on the x-axis. On the y-axis, on the red, is the step up in the number of DCD transplants. And so this has been a step up on the line itself shows you the major uptick in machine perfusion. And there's been a skyrocketing of machine perfusion across the US and now across Western Europe as well. And for example, at our center, we have now 50% of our transplants, and we did about 180 transplants last year, 50% of those transplants are DCD organs on machine perfusion, which is a major paradigm shift compared to prior state. All right, now let me switch gears again, and this will give you a flavor of potential surgical complications in liver transplants. And just to review the operation, the first anastomosis is the portal vein anastomosis. You can imagine this is the recipient portal vein being anastomosed with the donor portal vein. So that's one of the inflows, the vascular inflows. The outflow is the hepatic vein to the IBC, so that's your outflow. The third vascular anastomosis is the arterial anastomosis, which can be the potential Achilles heel because the hepatic artery caliber is small, so that's the hepatic artery anastomosis. And then those are the three vascular anastomosis, and then you have the bile duct anastomosis as your fourth anastomosis. And then I'll briefly touch on donor quality. This will become important. So we typically choose our organs well where there's less than 30% steatosis, and you try to minimize the call to ischemia time, and especially for donation after brain death. And as I'd already mentioned, now the paradigm has changed where we're using more DCD organs. That has really changed the landscape of transplantation. So switching gears again, let's talk about post-transplant management. And again, I'll take an organ system-based review. We'll talk about neurologic issues. We'll talk about specific cardiovascular issues. We'll touch on pulmonary issues, renal issues, and then we'll finish up with some of the hepatic and GI issues. And I wanna touch lastly on surgical complications as well. So neurologically, again, in all ICU patients or post-surgical patients, we're gonna see post-operative delirium, but there is now more and more retrospective data that pre-transplant hepatic and septic encephalopathy become risk factors for post-transplant delirium. And especially as we transplant more alcoholic liver disease, now there's an increasing awareness that the alcoholic brain syndrome in these acute alcoholic hepatitis cases or acute onchronics can be a risk factor for setting up post-operative delirium and encephalopathy. From a strategy standpoint, from a sedation analgesia, again, routine care, opioid monotherapy, second agent if needed, and there's no contraindication to IV acetaminophen in the post-liver transplant phase. So this has become almost standard of care at our center with respect to analgesic strategies. The one unique thing you gotta watch out for from a neurologic standpoint is the neurologic toxicity of tacrolimus, which is, as a lot of you know, is the backbone of immunosuppression. So you can have some unique diagnoses. One of them is posterior reversible leukoencephalopathy, which is an MRI diagnosis. You can have seizures, and then you can have just personality changes or confusion. So watch out for tacrolimus toxicity in particular. From a cardiovascular standpoint, some, again, unique issues. You can have Takotsubo's cardiomyopathy show up, and now there's been more and more publications on this, as an increasing cause of post-transplant systolic heart failure. And this can show up as classic findings on TTE with regional apical ballooning to regional wall motion abnormalities. From a diastolic dysfunction standpoint, this is some interesting physiology where it is interesting. As you transplant somebody, they were previously auto-afterload reduced because they're living at a low mean arterial pressure. Once the new liver goes in, the afterload can normalize, and you can start unmasking previously undiagnosed diastolic dysfunction that was not obvious on pre-transplant echo. So watch out for this physiology if you start seeing unexplained pleural effusions, hydrostatic pulmonary edema in this patient population. In a similar context, you can start having valvular dysfunction. The MR that looked mild on the pre-transplant echo suddenly can be moderate to severe, again, with a normalization of the afterload. So just something else to watch out for, especially for left-sided valvular dysfunction that can raise its head after transplantation. And then lastly, from a cardiovascular standpoint, as we transplant more mass serotics, we have to have an antennae out for cardiac ischemia in this patient population. From a lung standpoint, just sort of hooking it to the previous slide, watching out for post-operative hydrostatic pulmonary edema, especially if you unmask diastolic heart dysfunction or valvulopathy. Post-operative pleural effusions can have the same physiology. The other thing I wanna make a point is if a patient has pre-transplant hepatic out of thorax and with diaphragmatic defects, that will come back post-transplant. So you can anticipate that you will have a recurrence of a pleural effusion in somebody with pre-transplant hepatic out of thorax. And then tracheostomy, again, for hopefully this is not happening often, but if they have the right indications. And so that is something that there's no contraindication from an immunosuppression standpoint. From a GI standpoint, again, judicious use of opioid analgesia to minimize the risk of ileus. We use metal naltrexone, Relestor, often as needed. And this is something just standard of care. If you're having a biliary anastomosis that is a ruin why we typically do angio decompression. From a hepatic drug metabolism, you have to, again, assuming the liver, the new liver is working well, there shouldn't be any major barriers. There's no contraindications to routine hepatotoxic drugs. So IV amiodarone for your post-op AFib, IV acetaminophen as we spoke about. You have to watch out for some unique drug-drug interactions related to immunosuppressive agents such as tacrolimus and fluconazole. It'll be one example where it can affect the metabolism of tacrolimus. From a renal standpoint, just hooking back to the previous talks, post-operative AKI, again, especially if you take a high amount of patient to transplant with a high EBL, that is a perfect setup for intraoperative ATN. So you have to watch out for that. If a patient has pre-transplant HRS, that physiology can persist for days to weeks post-transplant. So you can anticipate the persistence of post-transplant AKI that may need continued therapy. And then as I'd mentioned, from an intrarenal standpoint, there is a risk for intraoperative ATN due to blood loss. And interestingly, there is now published data that as we increase the use of DCD organs that is associated with a potentially higher risk for acute kidney injury because of a cytokine surge that's coming out of the DCD organ. So something else that we're keeping our eye on as we increase the use of DCD organs. And then from a dialysis standpoint, as I'd already mentioned, if you have pre-transplant dialysis, you can anticipate that you will need to continue that post-transplant dialysis as the etiology of the acute kidney injury reverses. And then more and more centers are using intraoperative CRT to maintain electrolyte and acid-based homeostasis in the intraoperative setting. Just to summarize this slide, just for the sake of time, I'm just looking at the clock. I wanna make sure we have some time for questions if possible. Routine post-operative care for DBT prophylaxis, POD prophylaxis. From an ID standpoint, we have some standard of care practices. So we prophylax for PCP, HSV, and CMV, particularly with Bactrim and valgancyclovir. In the setting of high EBL cases, and that there's more consensus that you need empiric antifungal prophylaxis. For example, we use microfungin at our center. And then depending on the donor profiles, you may need to start therapy for hepatitis B and hepatitis C, as I'd mentioned before. And then one other unique issue in this patient population, if you have a new onset infection in this patient population, you have to add a donor-derived infection to your differential diagnosis, compared to all the other forms of critical care that we do. So that becomes important to chase the donor serologies and the donor cultures if that becomes an issue. So let me wrap up with surgical complications, just going back to the anatomy. So hepatic artery thrombosis is the one Achilles heel we have to watch out for. So everybody post-transplant gets a standard ultrasound to make sure the hepatic artery flow is patent. This is a problem if it goes down, because the hepatic artery is the sole blood supply for the biliary system. So you can start developing ischemical angiopathy, and that may be an indication for urgent retransplantation. So this is something that we really keep our antennae up for. The second common issue is biliary leak. And so there is something we're watching for with respect to the drain. Is the drain looking bilious or not? Right next to the biliary anastomosis. So that would be another indication for a take back to the oar. The other ones are relatively rare. So portal vein stenosis is very rare, but that can be treated with IR, or interventional radiology. Hepatic vein stenosis, again, is a relatively rare complication as well. I wanna mention a couple of specific complications with respect to the liver graft itself. Luckily, this is rare if you choose your organs well. Primary non-function. The liver goes in, it does not work. You'll start mimicking acute liver failure. The INR rises, the lactate rises, and that is an indication for urgent listing for retransplantation. So that is something that you can minimize by choosing your organs wisely. The other newer kid of the block, especially those in the audience who are dealing with transplant centers using DCD organs, is early allograft dysfunction. As we're pushing the envelope with DCD organs, we are seeing this phenomenon of a transaminitis, a hyperbilirubinemia, a mild INR elevation that luckily gets better with supportive care. But just something to watch out for, especially if you're using DCD organs. And just to wrap it up, subacute liver transplant complications. I mentioned this in the setting of those of you taking care of these patients a year, two years out. There are specific complications from immunosuppressants in particular. For example, sirolimus can induce a pericardial effusion. Lung complications you can have. Sirolimus induced acute pneumonitis, interstitial lung disease. From a renal standpoint, one of the limitations of Prograf is causing AKI and hyperkalemia. And then from an ID standpoint, again, you have to have your antennae up for infectious complications, so bacterial, fungal, and viral complications. A unique form of infection in this patient population is CMV. A lot of you may be familiar with this, is you have to watch out for somebody with pneumonitis or colitis that can potentially have a CMV trigger. And then from a neoplastic standpoint, there's a unique form of lymphoma called post-transplant lymphopoietic disorder, PTLD, that can manifest in any lymph node in any organ system. So just to summarize this part of the talk, optimal pre-transplant care involves, as you saw, application of evidence-based critical care principles from general critical care to manage hepatic and extrahepatic organ dysfunction as we aim to bridge that patient to life-saving liver transplant. The other point I'd share with you is successful post-liver transplant care is based on assessment of pre-transplant derangements such as HRS-AKI, hepatic out of thorax, and that's gonna help you successfully manage these patients post-transplant. From a cardiovascular standpoint, we spoke about anticipating certain complications once you normalize the afterload with respect to diastolic heart disease, unmasking diastolic heart dysfunction or valvular dysfunction. We spoke about the increasing use of DCD organs and the implications with respect to early allograft dysfunction and DCD-induced AKI. And we touched base on surgical complications including hepatic artery thrombosis and biliary complications. Thank you for your attention. Thank you.

liver transplant

multi-organ dysfunction

hepatitis C-positive donors

machine perfusion

post-operative care

immunosuppressive management