Good afternoon. My name is Dr. Adwoa Boateng-Evans, and I will be presenting the year in review which will chronicle the top 10 articles of anesthesiology critical care throughout 2021. I'm a clinical assistant professor at Stanford University Medical Center and work as an anesthesiologist intensivist. I have no disclosures to report. Our itinerary for the session is as follows. We will begin by discussing seminal literature relating to the treatment of COVID-19, which will bring us to high-yield papers surrounding hypoxia therapies. We will then transition to a core tenet of critical care, that is sedation, analgesia, resuscitation, and end with a key discussion of articles on traumatic brain injury and neurocritical care management. The HOT ICU trial published in the New England Journal of Medicine looks to answer the key question, what is the ideal oxygenation target in patients with acute hypoxic respiratory failure? That balances not only the risk of hypoxia, but also hyperoxia, which we know can include sequelae such as resorption atelectasis, lung injury, and oxidative stress. Clinical practice guidelines give great recommendations for patients who are suffering from ARDS and have recommended a conservative range with a PAO2 from 55 to 80 millimeters of mercury. However, for those outside of the setting of ARDS, there aren't clear recommendations as to an optimal oxygenation target. To do so, the study enrolled about 2,900 patients across 35 ICUs in Denmark, Switzerland, Finland, the Netherlands, and Norway. About 60% of the patients were admitted with pneumonia, about 60% requiring mechanical ventilation, and about 12% of the participants actually had ARDS. They were randomized to receive a lower oxygen target of about a PAO2 of 60 millimeters of mercury or a higher oxygen target of about a PAO2 of 90 millimeters of mercury. There was no significant difference found in 90-day all-cause mortality, days alive without life support, median percentage days alive after hospital discharge, or serious adverse events as prior data had indicated. Thus, targeting a PAO2 of about 60 to 90 continues to be appropriate with undue harm or risk for critically ill patients with acute hypoxic respiratory failure. Number two, the pre-oxygenation using high-flow nasal cannula versus tight face masks during rapid sequence induction was published in February 2021 in Anesthesia and sought to identify which method of oxygenation really mitigates the risk of hypoxia in this setting. So the study enrolled about 300 patients across six centers in Sweden and Switzerland who were undergoing elective surgery requiring rapid sequence induction. The patients were randomized to high-flow nasal cannula at about 100% or a tight-fitting face mask and monitored for an outcome of 93% or less from the time of induction to one minute post-intubation. There was no difference in the lowest mean oxygen saturation from the start of pre-oxygenation until one minute post-intubation. There was also no significant difference in the end-tidal CO2 levels in the first breath after intubation between the two groups. However, a subtle difference that was noticed was that the oxygen concentration in the first breath after intubation was higher in the face mask group than in the high-flow nasal cannula group. And the thought process behind this is likely due to some patients inspiring the study with their mouth open and diluting the 100% oxygen with room air, thus lowering the end-tidal oxygen concentration after that first breath. Similarly, because end-tidal oxygen has been used as a surrogate for the efficacy of pre-oxygenation, that variable was not able to be ascertained accurately during high-flow nasal oxygenation and thus does not take into effect the ethnic pre-oxygenation period. Similarly, the study did not include obese patients, pregnant women, and populations who we know are at risk for desaturation during apnea due to low FRCs, low functional residual capacities, and concomitant high metabolic demand. However, the study overall shows that high-flow nasal cannula is a suitable method for pre- and pre-oxygenation to maintain adequate oxygen levels during rapid sequence induction and is an alternative to traditional face-mass pre-oxygenation. Number three, the recovery trial. As a society of critical care medicine, we'd be entirely remiss if we did not discuss one of the most seminal pieces of critical care literature throughout 2021 and thus not discuss recovery. Recovery, for those who are unfamiliar, is the randomized evaluation of COVID-19 therapy trial, which actually began in 2021, and is an umbrella trial designed to assess the effectiveness and is an umbrella trial design that simultaneously looks at various treatment modalities for patients with SARS-CoV-2. We are specifically going to discuss the dexamethasone arm of that trial. The premise of the study being that steroids have been used favorably in disease states that mirror COVID-19, such as SARS, MERS, influenza, and even community-acquired pneumonia. And so the question remained if and how corticosteroids could be used in syndromes similar to COVID. And so the authors were able to erect an unblinded, adapted, randomized controlled trial that took place amidst 176 NHS hospitals in the UK, and patients were randomized to dexamethasone 6 milligrams once per day for 10 days, or less if they were discharged from the hospital, and compared to patients randomized to usual care alone. What was found was that the dexamethasone group reduced mortality, particularly in patients with ARDS, requiring mechanical ventilation, with a number needed to treat of 8. The age-adjusted mortality was about 21% in the dexamethasone group as compared to 24% in the placebo group. Similarly, the length of hospital stay was also reduced in the dexamethasone group from 13 days to 12 days. However, for patients not receiving respiratory support, there was no significant difference. Notably, the trial was unblinded, and usual care was actually not standardized given the time period by which this took place, which was about March to May 2020, and because ventilation methods, as well as treatment modalities, were evolving rapidly during that time period. Nonetheless, overall, the trial has led to a mainstay of COVID-19 therapy, and that is the use of dexamethasone for those with respiratory failure. Number four, the Co-Barrier Study, funded by Eli Lilly, was a double-blinded, placebo-controlled parallel group phase three randomized control trial that investigated the efficacy and safety of baricitinib in patients hospitalized with COVID-19. For those who are unfamiliar, baricitinib is a JAK2 inhibitor known to have anti-cytokine properties used in disease states such as rheumatoid arthritis and postulated to have some antiviral properties. And thus, included patients had to have serologies consistent with SARS-CoV-2 and at least one elevated inflammatory marker. This study took place in about 101 centers across 12 countries, with about a quarter of the study participants being located in Brazil. Baricitinib was studied in combination with remdesivir in a prior study called the ACT-2 trial, and this demonstrated a reduction in the time to recovery compared with those receiving However, it was not powered to detect a mortality difference. Thus, this study utilized a National Institute of Allergy and Infectious Disease ordinal scale and enrolled those who scored a five or higher, meaning that the patients were hospitalized and continuing to require medical care with or without supplemental respiratory support. These participants were given four milligrams of baricitinib daily versus placebo, and as an intention to treat analysis, baricitinib was administered in a single dose. However, as an intention to treat analysis, the study ultimately found no difference in the primary endpoint, which was progression of the previously mentioned scale, which reflects essentially worsening critical illness requiring the increased need for supplemental oxygen. However, there was a significant difference in one of the secondary outcomes, which looked at all-cause mortality at day 28 and day 60, with a number needed to treat of 20. Adverse events occurred with equal prevalence across the placebo and intervention groups, and in terms of the generalizability, notably, this difference was actually more pronounced in the subgroup of patients who were sicker at baseline. So overall, the study demonstrates that baricitinib appears to be safe and effective for critically ill patients with COVID-19. We've come to use it at my center as well as other centers throughout the United States. The MENS 2 trial asked the question, can we mitigate the risk of delirium and coma by using dexmedetomidine in lieu of propofol? Much of the impetus for the study arose from its precursor, the MENS study, which demonstrated that the use of dexmedetomidine resulted in more days alive without delirium and coma as compared to lorazepam. Thus, the MENS 2 study was a double-blind placebo-controlled randomized trial that enrolled about 400 patients in medical and surgical ICUs with suspected or confirmed infection, essentially sepsis, and respiratory failure requiring mechanical ventilation. The participants received anywhere from 0.1 to 1.5 mics per kilo per hour of dexmedetomidine with an average dose, excuse me, a median dose of 0.27, and a propofol infusion at between 5 to 50 mics per kilo per minute with a median dose of about 10. Both chitrated to actual body weight. The primary endpoint elucidated that there was no significant difference in days alive without delirium or coma during the 14-day study period. The secondary endpoint similarly showed no difference in ventilator-free days between the two groups at day 28, nor at death at day 90 or global cognition at six months. And lastly, there was no difference in safety endpoints, significant organ dysfunction between the two groups. There was one reported incidence of propofol infusion syndrome, but that was later dismissed after further analysis of the study participant. So overall, the study demonstrates near equivalence of two commonly used sedatives among critically ill patients for neurologic-related outcomes. The BASICS trial is a randomized control trial that was conducted across 75 ICUs in Brazil, which enrolled about 11,000 patients looking to see if there was a mortality benefit with the use of a balanced crystalloid solution as compared to isotonic saline. Thus, they enrolled patients who were requiring fluid resuscitation due to hyperperfusion, but also demonstrating fluid responsiveness and had at least one factor for acute kidney injury. They additionally wanted to assess whether there was a mortality benefit in FAS, which was defined by about a liter per hour versus slow infusion rates. So they assessed both the type of fluid as well as the speed of infusion. And the study builds off of prior data published in the SPLIT and SMART trials, which some of us are familiar with. Those trials actually demonstrated opposite outcomes, the former showing no difference in 90-day AKI, while the latter showed a significant increase in some of the incidents of 30-day mortality events, such as AKI. Thus, in the BASICS trial, the fluid that the patient was randomized to was used for the entirety of their ICU stay with the exception of certain pathophysiologic states that would require alternative IV infusions, such as hypernatremia. However, once safely feasible to do so, the study fluid was resumed. Regarding the primary outcome, there was no difference in 90-day mortality. However, there was a statistically significant difference in one of the secondary outcomes, including the SOFID score at day 7 in the balanced solution group. There were no significant differences in the additional 17 secondary outcomes, which also included renal replacement therapy during admission, ventilator-free days, and CADECO scores above 2 at days 3 and 7. However, the subgroup analysis did reveal an interesting statistically significant interaction between the presence of traumatic brain injury, fluid type, and 90-day mortality. As for the rapid versus slow rate of infusion, there was no difference in the primary outcome, 90-day mortality. As for the secondary outcomes, we did see differences in the cardiovascular, respiratory, and coagulation SOFA scores. And these were actually statistically significant. However, they were not found by day 7. And the SOFA scores had also dissipated by that time. The differences in the SOFA scores had dissipated by that time. So overall, the study neither demonstrates a mortality benefit with the selection of balanced versus isotonic saline, nor with the rate of infusion. However, the subgroup analysis among TBI patients cannot be overlooked, suggesting the role for isotonic saline in that demographic. The VAM-IHCA trial sought to answer the question, in patients who suffer in-hospital cardiac arrest, does vasopressin plus methylprednisolone increase the likelihood of achieving ROSC? Part of the impetus for this study was previous literature that demonstrates that endogenous vasopressin levels are actually lower in non-survivals of cardiac arrest. So here, 10 hospitals across Denmark randomized about 500 patients to the intervention arm, or placebo, the intervention including 40 milligrams of methylprednisolone and 20 international units of vasopressin. The SOFA scores were collected at 24, 48, and 72 hours post-arrest. And neurologic outcomes were assessed at 30, 90, 180, and one year post-arrest. Final participants were about age 70, with a male predominance, and about equal rates of comorbidities between the two groups. The primary rhythm identified in the arrest were PEA. The primary outcome showed a statistically significant higher rate of ROSC in the intervention vasopressin methylprednisolone group. However, there was no significant difference at 30 or 90 days of survival, demonstrating favorable neurologic outcome. So while the study demonstrates a favorable outcome in terms of ROSC, it remains to be demonstrated if this correlates to long-term survival benefit. And we see that exemplified here with a risk ratio of 1.3 for ROSC. However, a risk ratio of about 0.8 for 30-day survival. Number eight, the COBE trial looked to assess, can a continuous infusion of 20% hypertonic saline improve neurologic outcomes at six months in traumatic brain injury patients by essentially staving off intracranial hypertension? However, hypertonic solutions, as we know, are wrought with myriad side effects. And so does the benefit outweigh the risk in this patient population? The study design here was a multicenter, parallel group, open-labeled, randomized control trial conducted across nine French hospitals with high-volume traumatic brain injury patients. Participants had to have moderate to severe TBI, as documented by a GCS equal to or less than 12 in positive CAT scan findings. After patients were randomized, a one-hour infusion of either the intervention or placebo therapy was given within 24 hours and modified for the patient's baseline sodium so as not to exceed a sodium of 155, which was the author's threshold for hypernatremia. Notably, those administering the intervention were not blinded. The control arm had a standard therapy of intracranial hypertension, which include boluses of sedative drugs and hyperosmolar therapy as needed. The primary outcome showed no significant difference in the six-month Glasgow outcome scale between the two groups at six months with an adjusted odds ratio of about 1.02. As for the secondary outcomes, there were also no differences in ICH nor with median length of ICU stay. Note that rates of severe hypernatremia were about 12% in the intervention group and about 6% in the control group. The intervention was also associated with reduction of the risk of intracranial hypertension. However, more patients in the intervention group did develop delayed intracranial hypertension, suggesting something like a rebound effect with therapy cessation. So overall, the findings do not support the use of 20% hypertonic saline toward better neurologic status at six months. The ULTRA study sought to answer the question, does early treatment with TSA improve outcomes at six months in patients with subarachnoid hemorrhage? The study was conducted across 24 sites in the Netherlands, enrolling about 1,000 patients with admission-documented subarachnoid hemorrhage on a non-contrast CT scan. The intervention arm were randomized to receive either placebo or a one-gram bolus of transexamic acid plus one-gram QA hours as compared to the standard treatment. The primary outcome found no difference in the modified Rankin scale at six months, which was assessed via a standard telephone interview. The secondary outcome was actually notable for a difference in quote-unquote excellent outcomes, which was denoted by a modified Rankin scale of 0 to 2 at six months, and that was significantly lower in the TSA group. However, there was no difference in thromboembolic events during intervascular treatment, all-cause mortality at six months, serious adverse events, re-bleeding before securing the aneurysm, or delayed cerebral ischemia. Thus, overall, the study does not show any clear clinical benefit from transexamic acid use in subarachnoid hemorrhage, particularly given the risk for delayed cerebral ischemia. And last but not least, we will finish with another seminal trial in a series looking at targeted temperature management, TTM2. Temperature management after cardiac arrest is a very well-studied area of literature within critical care, though with very disparate findings. Unanimously, we understand that fever and certainly hyperthermia have been demonstrated to be deleterious and affiliated with worse outcomes. However, the ideal temperature after arrest in patients who are unconscious remains to be elucidated. And so here, the authors compared targeted hypothermia versus targeted normalthermia and their impact on all-cause mortality. They did this by conducting an international, multi-centered, randomized superior trial that was non-blinded across 14 countries and 61 institutions, predominantly in Europe, with specific inclusion criteria being out-of-hospital cardiac arrest in a state of unconsciousness after arrest. Participants had similar baseline characteristics, but there was no clear clinical benefit from For the hypothermia group, rapid cooling was achieved by cool fluids or physical cooling devices, either surface or intravascular, and patients were re-warmed after 28 hours. In the normalthermia arm, participants who developed a temperature over 37.8, which was the trigger, were cooled similarly with surface cooling devices or intravascular cooling, which were set at 37.5 degrees centigrade. Of those, about 46% of patients actually did require that cooling device to achieve the target temperature. The primary outcome found no difference in all-cause mortality at six months. Neither was there a difference appreciated in the secondary outcomes, which included functional status and health-related quality of life. And that concludes our talk for this session. Thank you all for attending, and I wish you an enjoyable rest of the conference. Hi, this is Alexey Pustovoytov. 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 Co-op Tech and stock ownership in GE, Butterfly Network, SanoBioTechnology, Moderna, AstraZeneca, eHealth, and Attea Pharmaceuticals. After 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 rise 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, hepatopalmary syndrome, portopalmary 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 acute liver failure. They can develop serious bacterial peritonitis or catheter-related bloodstream infections. Endocrine system is not working well either due to adrenal insufficiency and hypoglycemia is very common. Patients 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 and subsequent procedures for hemostasis, bile 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 recipients. One involves discontinuous care in multiple units during pre-operative 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 and not transplanted. Interoperative 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. Interoperatively, 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 and 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 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 organs selection committee to optimize patient outcomes 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, and access to advanced endoscopic and 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 a 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 a 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 a 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 melt sodium scores 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, is 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 the rapid response teams were called on critical events in this patient population. Only 28% of patients in those groups had DNA 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. Hi to everyone watching. My name is Emily Naum and I am a dual trained critical care physician and obstetric anesthesiologist at Massachusetts General Hospital. I'm here today to speak about perioperative intensive care of the high risk obstetrics patient. To quickly go through goals for this session, I'll review current trends in maternal morbidity and mortality, ICU admission characteristics in this population. We'll go through pregnancy physiology and how that affects our ability to detect deterioration in pregnant women and identify opportunities for non-traditional critical care administration models in these patients. So let's start with some epidemiology. Severe maternal morbidity are CDC defined unexpected outcomes of labor and delivery that result in significant short or long-term consequences to a woman's health. There are 21 indicators with conditions in various systems as noted here. The rate of severe maternal morbidity is rising over the last two decades by almost 200% overall since 1993. This increase has been mostly driven by blood transfusions, but even when you exclude those, the rate of severe maternal morbidity increased by about 20% over time from 1993 to 2014. Severe maternal morbidity is associated with ICU admission as well as mortality. Recognizing who's at risk for these complications when they appear on the labor floor is important to maintain vigilance and monitoring in those people who are most likely to experience morbidity. A study was done in 2013 of more than 850,000 women using Medicaid data to look at conditions associated with the CDC defined diagnoses for severe maternal morbidity. The conditions were weighted and a comorbidity index was created and subsequently validated in the clinical setting. I'll talk more about this later as a way to flag at-risk patients, so let's put a pin in this for now. Medical conditions associated with increased morbidity include chronic heart, liver, and renal disease, lupus, and HIV. Obstetric conditions include preeclampsia and other features, multiple distation, and prior cesarean delivery. Social risk factors include public or absent health insurance as well as lower education levels and lower incomes. Significant racial and ethnic disparities have also persisted in maternal morbidity and mortality. This gap exists in every racial and ethnic minority category compared with deliveries among non-Hispanic white women. Non-Hispanic black women are particularly affected with severe maternal morbidity occurring in 230 per 10,000 delivery hospitalizations compared to only 139 in non-Hispanic white women. Maternal mortality is a very real problem in both low-income and high-income countries. As you can see here, the US maternal mortality rate is quoted at 17.3 per 100,000 live births based on a study of pregnancy-related mortality by the CDC. This is substantially increased over the last two decades from 10 in 100,000 in 1990, which is closer to the current mortality rate in the UK. An important point to be made here is that several large-scale studies have shown that ICU admission and maternal mortalities have been deemed potentially avoidable in a significant number of cases. Two of the most common factors include lack of recognition of complexity or seriousness of the condition by the caregiver and a lack of knowledge and skills by staff. This figure comes from a retrospective study of maternal mortality in the United States. It demonstrates the leading cause of maternal death in the US is cardiovascular conditions with slightly more than a quarter of deaths followed by pre-existing illness, sepsis, and then hemorrhage. Of note, this study did not include psychiatric conditions, which has been increasingly highlighted as a leading cause of maternal morbidity. A recent article in JAMA Network Open found that the number four leading cause of pregnancy-related maternal death is perinatal mood and anxiety disorders. Reviewing the trends, the rates of maternal deaths from hemorrhage, hypertensive disorders of pregnancy, and anesthesia complications have decreased over time. However, one condition that deserves highlighting is that of maternal sepsis, with a mortality rate that remains around 12% over the last three decades, despite the publication and implementation of the surviving sepsis guidelines. This figure comes from the UK Embrace, which is a collaboration that conducts surveillance and inquiry into maternal deaths. It shows similar trends to the U.S. reports with cardiac disease leading the causes of death, followed by thromboembolism, neurologic morbidity, and here they include psychiatric disease. Following this, we see that pre-existing illness and sepsis that we see in higher numbers in the U.S. maternal mortality study. Importantly, they found that deaths related to pregnancy-related infections actually increased from 2012 to 2018, again highlighting the need for better detection and management in this at-risk population. Inequality in maternal health and outcomes remains an ongoing battle. This figure comes from the CDC, and it demonstrates clear racial disparities in the incidence of pregnancy-related mortality. Variability in the risk of death by race and ethnicity may be due to several factors, including access to care, quality of care, prevalence of chronic diseases, structural racism, and implicit biases. So how often do we actually see pregnant patients in the ICU? The estimates in ICU admission are challenging due to lack of consistency in definition, and it's likely underestimated due to confounders like excluding women who were critically ill but not ultimately admitted to an ICU or women who didn't suffer significant organ failure. Overall, 1% to 3% of peripartum women require ICU admission or critical care services in the U.S. each year. This is comparable to rates in other developed nations. Most of these admissions are postpartum. The causes of ICU admission do not actually differ significantly in high-income versus low- and middle-income countries, although there is a significantly higher maternal mortality rate in low- and middle-income countries compared to high-income. Hemorrhage and hypertensive disorders of pregnancy account for the majority of maternal ICU admissions, although the exact case mix differs widely in each country and even within different regions. This is likely multifactorial and related to differences in preconception counseling, prenatal care, socioeconomic and environmental factors, surgical practices, and regional ICU admission guidelines. This figure shows the causes of maternal ICU admission in high-income countries across several studies ranging from 2006 to 2019. These were all retrospective analyses of admission diagnoses in the U.S., Canada, the Netherlands, Italy, France, and New Zealand. This table comes from a study of obstetric ICU admissions in New Jersey that highlights significant risk factors for ICU admission, including hypertensive disorders of pregnancy, cesarean delivery, multiple gestation, and hemorrhage. This study looked at over 18 million live births in the U.S. between 2012 and 2016. The authors developed a predictive model looking at factors associated with maternal ICU admission and identified cesarean delivery, hypertensive disorders, and induction of labor as the highest risk factors for critical care needs. Other notable risk factors include a BMI greater than 50, and again, to highlight the racial disparities with Black and Hispanic women having an increased risk of admission compared with white women. I mentioned before that we would circle back to severe maternal morbidity. We discussed the 2013 study that created the comorbidity index score where various maternal and obstetric conditions are assigned a weighted number and the total score is calculated. This score was primarily calculated to estimate morbidity, but this figure shows one of the secondary outcomes of that study was ICU admission, which was also found to be associated with higher comorbidity index scores, or CMI scores. Clinically, simplified tools have allowed us to determine these scores and they can be used to make a universal baseline assessment of every patient on a labor and delivery floor. A higher initial CMI score draws attention to those patients who may require closer monitoring and help to influence providers to escalate care more promptly. If you know that they're at risk of being sick, you may be more likely to tune in to even subtle abnormalities when they develop and capture evolving complications earlier in their time course. One cannot give a maternal critical care lecture without a brief review of the physiologic changes of pregnancy. Cardiovascular changes of pregnancy are related to the hyperdynamic state. Increased cardiac output comes from an increased stroke volume and heart rate and increased contractility. SVR and PVR decrease throughout pregnancy, resulting in lower systolic blood pressures, which nature in the second trimester. Pulmonary changes include an increased tidal volume related to increased anterior-posterior diameter of the chest, and this results in a respiratory alkalosis that's compensated by renal bicarbonate excretion. There's a physiologic anemia of pregnancy due to a disproportionate increase in plasma volume compared to red blood cell volume. Most clotting factors increase, resulting in a hypercoagulable state. White blood cell count increases in pregnancy, and this is generally a reflection of an increase in the number of polymorphonuclear cells with the appearance of immature granulocytic forms. Levels of IgA, IgG, and IgM are unchanged during gestation, but humoral antibody titers to certain viruses are decreased. Renal blood flow and creatinine clearance increase throughout the pregnancy, resulting in a lower serum creatinine. And progesterone effects on the GI system include biliary stasis. This contributes to the increased incidence of gallbladder disease during pregnancy. And finally, increased abdominal pressure and reduced lower esophageal sphincter tone increase the risk of gastric aspiration in pregnant patients. Keeping in mind these physiologic changes, I want to reflect upon the scoring systems that we have to detect sepsis in the general population and challenge you to apply them in the peripartum period. The SIRS criteria actually describes normal pregnancy physiology in three out of the four values that we look at. These have been found to be very sensitive, but poorly specific in pregnancy. The QSOFA score is more specific. However, the sensitivity has been found to be only 50% in pregnant patients who had known sepsis due to the rarity of mental status changes and unreliable estimates of respiratory rates. The SOFA score has better predictive value for patients who are admitted to the ICU for in-hospital mortality than SIRS or QSOFA, but poor specificity for maternal sepsis, again, due to the physiologic changes of pregnancy. And finally, the APACHE-2 score consistently overestimates mortality risks for pregnant and recently pregnant women. Because of these issues detecting vital sign changes in pregnant patients, comprehensive early warning systems have been developed specifically for obstetric patients. These include the Maternal Early Warning Criteria, or MEW criteria, and the Modified Early Warning Score. And variants of these have been studied and implemented across the world. The MEW criteria require one or more of several physiologic alterations to trigger a clinician evaluation and possible escalation of care if needed. A case control study in 2018, looking at patients with maternal sepsis showed that the MEW criteria had a sensitivity of 82% and a specificity of 87%, and that this performed significantly better than SIRS or QSOFA. Another score, the Modified Early Obstetric Warning Score uses similar physiologic variables to the MEW criteria, but with additional components that are noted here. It includes different levels of trigger based on the degree of abnormality. A case control validation study looking at overall maternal ICU admission, so not just for sepsis, showed that this modified score had a high sensitivity at 96% and a specificity of 73% when using one or more red trigger values. Notably, the four variables that were significantly associated with ICU admission at greater than 24 hours were maximum temperature, heart rate, systolic blood pressure, and respiratory rate. Integrating these warning systems into clinical pathways has real appeal to standardized evaluation and early intervention in at-risk or deteriorating patients. This figure comes from a study published by a group in California where they reported nearly 120,000 deliveries after implementation of this tool. It includes early warning triggers and pathway-specific recommendations to expedite treatment for the most common areas of morbidity, sepsis, cardiac dysfunction, hypertension, and hemorrhage. This group actually noted a statistically significant reduction in severe maternal morbidity when comparing baseline data to after implementation of the tool. Identifying patients who are developing critical illness is really challenging, and overcoming the cognitive bias that most of these patients are healthy young women who couldn't possibly be developing critical illness is another real challenge. These kinds of systems help to create a universal check-in for providers on labor delivery floors to object to the use of critical illness to objectively evaluate the patients and proactively manage complications to prevent further morbidity. Our biggest challenge is when these patients exist in the gray part of the spectrum of critical illness. Sometimes though, there are clear indications for admission. Mechanical ventilation, vasopressor support or invasive monitoring, ongoing bleeding, acute liver, cardiac, or neurologic failure all generally require an ICU admission at most institutions. As our pregnant population evolves into more complex patients with more chronic illness, we should consider directions for the future. An important evolution in practice is determining the best location to deliver care to critically ill obstetric patients, particularly those who are not yet delivered. The advantages of delivering on the labor floor are increased physical space, familiarity with obstetric interventions and access to operating rooms, and a reduced risk of nosocomial infections. Conversely, the advantages of delivering in the ICU are immediate availability of ICU providers, advanced monitoring and higher level interventions. The choice really depends on the degree of patient instability and the interventions required. The emphasis should remain on maternal wellbeing as the primary goal. Providers who regularly work in labor and delivery have the greatest familiarity with obstetric interventions, obstetric medications, which are not routine in the ICU and close access to operating room facilities for potential delivery. Although many intensivists consider the safest place for all patients in the hospital to be the ICU, this is a rare and highly specialized patient population. The majority of intensivists do not routinely care for pregnant patients and especially not in the immediate peri-delivery period. So those providers who do have experience with obstetric, obstetric anesthesia, high-risk medical and or surgical care to pregnant patients on a more regular basis should be available to provide direct or consultant care. Finally, recall that I mentioned psychiatric illness is a leading cause of death and depression and PTSD are very real complications from ICU admission. The importance of emotional attachment and maternal fetal bonding must not be overlooked. An alluring prospect is the idea of graduated escalation of critical care delivery. A nice article published in 2019 outlines the cosmic paradigm. This is a four-step system of early multidisciplinary consultation, automated surveillance, monitoring and intensive care aimed to identify high-risk and clinically deteriorating patients. The proposed concept is that at-risk patients are best managed on the labor and delivery floor with a remote ICU telemedicine service except in the most extraordinary cases. This model provides a monitoring framework on labor and delivery using nurses who have both ICU and obstetric training, ICU level patient monitoring and telemedicine consultation and select high-risk OB patients to add an additional layer of vigilance for patients who may not otherwise be sick enough for ICU admission, but when you want to bring an ICU level of care to labor and delivery. Proponents of this model highlight the importance of immediate proximity to obstetricians, obstetric anesthesiologists and the operating room. I wanna close by taking a high-level view in maternal critical care with a big step back. Adoption counseling and medical optimization is crucial in high-risk obstetric patients. Upon admission, patients should be assessed for risk of morbidity and they should be continuously monitored for development of complications using maternal specific warning systems. If critical illness develops, there are bundles in place for common maternal conditions that are associated with morbidity and these emphasize prompt assessment and treatment, multidisciplinary involvement of care teams and escalation of care when appropriate. Thank you for taking the time to listen. My email is listed here on this slide. I welcome any and all feedback or conversation surrounding maternal critical care. Please feel free to contact me. Looking forward to meeting in real life whenever we're back to in-person meetings. Thank you so much again for listening.

perioperative intensive care

high-risk obstetric patients

severe maternal morbidity

mortality rates

hemorrhage

hypertensive disorders

racial and ethnic disparities

early recognition of complications

comprehensive early warning systems