Ustavojtov. I'm an associate professor in the Department of Anesthesiology and Critical Care Medicine at the Johns Hopkins School of Medicine. Today we're going to talk about perioperative intensive care of the liver transplant recipient. My disclosures include equity ownership in CoopTech and stock ownership in GE, Butterfly Network, SanoBioTechnology, Moderna, AstraZeneca, eHealth, and Attea Pharmaceuticals. So listening to this presentation, you will be able to identify routine and unique needs of patients with end-stage liver disease, describe different models of transplant critical care, discuss multidisciplinary approach and specific roles of transplant surgeons and critical care physicians, and evaluate roles of specialized transplant ICU in modifying patient outcomes. So let's start with identifying routine and unique needs of our patients. According to Scientific Registry of Transplant Recipients, in 2019, there were approximately 12,500 listed liver transplant candidates. Almost 9,000 of patients were transplanted. Out of those who were removed from the list, 62% were transplanted, 18% died or were too sick for transplant, and almost 7% improved without transplant. What we also know that from 2009 to 2019, patients were sicker going into the transplant. About 23% of the patients had MELD score of 35 and higher, and almost 14% of the patients started from ICU before the liver transplant. During perioperative management of liver transplantation, ICU needs of patients can arise either pre-transplant due to manifestations of end-stage liver disease, acute and chronic liver failure, or acute liver failure, resultant multi-organ dysfunction syndrome, and may result in optimization of candidacy. Post-transplant, the needs can include recipient recovery, allograft function, immunosuppression. During both pre-transplant and post-transplant period, palliative care improvement can be a key to patient management too. Why do patients need critical care before transplant? Their brain may not be working well due to acute liver failure with cerebral edema or hepatic encephalopathy. Their lungs are not normal either. They may have pleural effusions, hepato-pulmonary syndrome, porta-pulmonary hypertension. They may be hypotensive or develop cardiomyopathy. Their kidneys are not normal either due to acute renal failure or hepatorenal syndrome with associated acid-base and electrolyte disorders like hyperkalemia or metabolic acidosis. Their hematologic system is not working well either. They can have rebalanced hemostasis with either bleeding or excessive coagulation. They develop portal hypertension with varices, ascites, gastropathy. They can be severely malnourished. They also develop sepsis due to either spontaneous bacterial peritonitis or catheter-related bloodstream infections. Endocrine system is not working well either due to adrenal insufficiency and hypoglycemia is very common. This recovery in post-transplant period is driven by emergence from general anesthesia, recovering multi-organ dysfunction and establishing liver graft function. In addition, on occasion there is a need for damage control surgical procedures when abdomen remains open and subsequent procedures for hemostasis, bowel duct reconstruction and abdominal wall closure. Many of the problems that were pre-existing in pre-operative period persist. Specific needs post-operatively may include the need for pain analgesia and delirium management, patient early mobilization. Commonly early extubation practices are implemented either in the operating room or early on in the ICU. Also patients become immunosuppressed to avoid liver graft rejection. Glycemic control unlike pre-operatively is more commonly centered on management of hyperglycemia. Patients still remain prone to sepsis either early or late infections. Okay, now let's talk about different models of transplant critical care. There are two main models of critical care for liver transplant recipient. One involves discontinuous care in multiple units during perioperative period. For example, pre-operative care can occur in medical ICU and not only will involve patients who ended up transplanted, but also will involve care of patients who are never listed or listed not transplanted. Intraoperative care occurs in the operating room and provided by anesthesia and surgeons and post-operative management occurs in the surgical unit and involves recovery from the surgical procedure and multi-organ dysfunction as well as immunosuppression. The alternative model involves holistic management by the same multidisciplinary team. Under those circumstances, the same team would take care of the patient pre-operatively and post-operatively. Intraoperatively, it will be the same surgeons taking care of the patient and anesthesiologists are commonly part of the same multidisciplinary team who participate in pre-operative patient selection, but also commonly are intensivists who have extensive expertise in taking care of liver transplant recipients. The advantages of continuous model of care include continuity of care as well as concentrated expertise in taking care of this patient population. It involves medical support, nutritional support, mental health and social support of liver transplant recipients, physical rehabilitation and palliative care when needed. Also, such a unit provides a great opportunity for utilization of liver support as well as vehicle for research. The disadvantages of continuous model of care stem from relatively small size of the patient population which would be served in those units. The example is given here. In the United States, there is approximately 26,000 patients with cirrhosis being admitted to ICU, which is only half percent out of all ICU admissions. Additionally, there is approximately 2,000 patients with acute liver failure and there is 9,000 liver and simultaneous liver kidney transplants in the United States, with only about 14% of those coming out of ICU. There are 115 centers approximately in the country that perform five liver transplants or more and when averaging it per center, there will be approximately 322 admissions per center and 78 transplants per center. Patients with cirrhosis spend more days in the ICU than the patients after the transplant and after taking into account length of stay of both cirrhotic patients and patients after liver transplant, we will come up that the average size of the patient unit is only seven patients. It also brings up the point that the transplant conversion rate is only about four and a half percent. This brings the financial viability of such units into play. The second big point to serve this relatively small patient population, staffing needs to be trained and finding staffing with appropriate level of training may be very difficult. Let's now talk about what multidisciplinary approach entails and what are the specific roles of transplant surgeons and critical care physicians. In 2011, American Society of Transplant Surgeons published a white paper on the leading role of transplant surgeon as the intensivist of choice for patients undergoing liver transplantation. While that may have merit, in modern days, multidisciplinary critical care, such an approach may have its own shortcomings. Here I summarize the role of the intensivist and the transplant surgeon in the transplantation. The intensivist does usually have routine leadership role in the ICU and they have organ support expertise which can apply across a variety of patient populations. They're also continuously present and they always look into optimization of outcome of their patient populations. Transplant surgeon does have a routine leadership role in transplantation and they lead candidate and organ selection committee to optimize patient outcome through selection of appropriate candidates. They also have technical expertise to perform organ transplantation as well as understand what these potential complications are. However, their role in the ICU is commonly limited to episodic presence only. So our suggestion that overall multidisciplinary approach is the best way to care for this patient population. So what is the multidisciplinary team for liver transplant patients? That team may include hepatologists, transplant surgeons, anesthesiologists, intensivists, as well as nurses, respiratory therapists, nutritionists, pharmacists, physical therapists, social workers, access to advanced endoscopic interventional radiology services. And those are by far not quite all the specialists that are needed to achieve the optimal outcomes in this patient population. An example of a successful multidisciplinary program is King's College experience. King's College has liver intensive care unit consisting of 15 beds and four additional high dependency beds. Over 800 patients are treated in this unit each year. In King's College, over 200 liver transplants performed per year. This unit is an internationally renowned acute liver failure center and also is leading research in this area. This is an intensivist driven multidisciplinary unit with daily input from surgeons, hepatologists, and other specialists. In the United States too, certain high volume centers which perform over 100 transplantations per year open their own multidisciplinary unit such as at Mount Sinai, New York, or UCLA. Finally, let's talk about how specialized transplant ICUs can modify patient outcomes. In 2011, Lott et al. in their original study looking into outcomes of patients admitted to general versus diagnosis appropriate specialty ICU or diagnosis inappropriate specialty ICU demonstrated that there were no differences in risk adjusted mortality between general versus ideal specialty ICU for all conditions except for pneumonia. However, there was a greater risk adjusted mortality for patients admitted to non-ideal specialty ICU. What implications does it have for liver transplantation is very difficult to say since that patient population was not included in the study. However, it also specified that specialty ICUs were like medical ICU versus surgical ICU and patients with end-stage liver failure as well as post-transplant patients do not fit exactly into any one of those categories. What do we know then about specialized liver ICU? So in this study, Zimmerman et al. described an experience of a multidisciplinary team led by transplant surgeons and looked at patients before and after implementation of specialized ICU. They would transplant patients out of ICU if they fulfilled the minimal criteria including absence of active infection, minimal ventilator requirements, stable hemodynamic status, and acceptable nutritional status. After implementation of liver ICU, they found that significantly more patients with MELD score 35 or greater or status one were added to the wait list, transplanted while on the list, as well as fewer were removed from the wait list. We know that mortality of patients with advanced liver disease admitted to ICU is very high, such that at six months only about 25% of patients survive. We also know that only 3.8% of those patients get transplanted. What if one is able to list more patients, transplant more patients, and if they are not transplanted, optimize their care or provide palliative care in a higher quality? That would be a significant goal of liver ICU. Sufficient tools were developed to understand prognosis of liver disease and the conditions of acute liver failure, acute and chronic liver failure, and progressive cirrhosis based on the trajectory of liver disease. Here are the most commonly used scores for end-stage liver disease, acute and chronic liver failure, and acute liver failure. For example, for acute liver failure, King's College criteria can be utilized. For acute and chronic liver failure, SOFR score, CLIF-SOFR score can be utilized. Whereas for end-stage liver disease, MELD and MELD-sodium score is the most commonly used. Out of our understanding of prognosis of patients with advanced liver disease, there are only four goals that are relevant to specialized liver ICUs. It's to optimize patient care, list as many patients as possible, and transplant as many as possible. Finally, if none of that applies, palliative care should be provided as needed. An example is given here. In this study, out of patients who were denied transplantation, majority of them died. And many of them may have benefited from palliative care. Whereas out of those patients who were listed, majority of them survived, whether they did or did not receive transplant. Well, transplant usually being denied under those circumstances when patient's disease improves. Well, I mentioned palliative care a few times before. The lack of a structured approach to palliative care in this population is stunning. The example is given here. In this study, patients who were referred for palliative care, who received actually palliative care, the median hospital stay was 14 days and the median time to death was 52 days. However, during that time, about half of them still required ICU admission, more than half required additional hospital admission, required therapeutic paracentesis, gastroscopy, and rapid response teams were called on critical events in this patient population. Only 28% of patients in those groups had DNR orders, and only 11 of those patients were referred to palliative care. Many of these patients experienced pain, nausea, lack of appetite, and the overall palliative care experience can be described as inadequate in this patient population. So in conclusion, we can say that a peer-operative management of liver transplant recipients benefits from specialized multidisciplinary ICU care. Specialized liver transplant ICUs are feasible in large volume programs for financial and staffing sustainability. Goals of specialized ICU care of liver transplant recipients are to improve candidacy, optimize candidacy, optimize outcomes of non-candidates, optimize transplant outcomes, and provide palliative care to non-survivors. And I would like to finish with this slide, which states that experience is something you don't get until just after you need it. This applies to specialized liver ICUs. The more patients there are in those ICUs, the greater the provider experience, the better the outcome of each subsequent patient, and more research opportunities will drive research in this area.

perioperative intensive care

liver transplant recipients

multidisciplinary approach

specialized liver transplant ICUs

patient outcomes