Good afternoon. My name is Dr. Jonathan Trager, and I am an attending physician in the departments of emergency medicine and critical care medicine at St. Luke's University Hospital in Bethlehem, Pennsylvania. I am also the medical director of our hospital's emergency and transport program, as well as our critical care transport division, and a practicing pre-hospital physician in Pennsylvania. I'm going to speak to you today on the topic of pre-hospital care and initial stabilization and transfer of the critically ill patient. I have no disclosures at this time. The objectives of this talk are to review literature related to pre-hospital critical care interventions. The focus of this topic will be on stop the bleeding or hemorrhage control options. The article that I have chosen to review is pre-hospital whole blood reduces early mortality in patients with hemorrhagic shock by Dr. Maxwell Braverman and his colleagues. Whole blood transfusion has been experiencing a resurgence of interest, mostly after our recent conflicts in Iraq and Afghanistan where resuscitation with whole blood was implemented and practiced in essentially all phases of care for the injured soldiers and has also been incorporated into the guidelines for tactical combat casualty care as a first-line agent hemorrhagic shock resuscitation. It's also preferred because of its ease of administration compared to standard therapy, which has been component therapy or as most of us are familiar with the one-to-one-to-one ratio of packed with blood cells to fresh frozen plasma and platelets. Furthermore, our pre-hospital colleagues do have limited therapeutic capabilities when treating trauma patients, especially those with significant hemorrhage and or penetrating injuries. This therapy will provide them with an additional option that may actually have benefits in saving their patients who are injured. The study objectives as outlined in the paper are to determine if pre-hospital low-titer O-hole blood, LTOWB transfusions compared to no pre-hospital LTOWB transfusions, improve survival in three distinct groups of trauma patients. Those receiving in-hospital transfusions only, those sustaining pre-hospital cardiac arrest, and those patients with development of shock physiology in the field. Not yet ready for prime time in the United States necessarily, but perhaps opportunities for the future, especially in situations of mass casualty incidents or mass gathering events, would be implementation of what the 75th Ranger Regiment was able to accomplish using a walking blood bank known as their ROLO program or Ranger Olo Titer program for battlefield blood transfusions by identifying the most ideal candidates for donation and pulling blood from them on the battlefield for rapid transfusion. To conduct this study, the Institutional Trauma Registry at a specified academic level when trauma center was queried from the years 2015-2019 for consecutive adult patients who underwent blood transfusions after their arrival to the emergency department. Incomplete records were defined as those that had no documented pre-hospital vital signs or incomplete pre-hospital vital signs that were required for the comparative analysis or those for whom a pre-hospital paper record was unavailable, thus rendering assessment and evaluation of the blood pressure and other vital signs impossible. Patients were then stratified based on receiving pre-hospital low titer O-hole blood identified as PHT or no pre-hospital low titer O-hole blood identified as the NT group. Patients in the NT group either received crystalloid infusion or no infusions while en route to the trauma center. A variety of data was compared to include patient demographics, injury characteristics, pre-hospital vital signs, and arrival vital signs, as well as the mortality in the emergency department at 6 hours, 12 hours, and overall length of stay. Comparisons were also made between the incidence of either massive transfusions defined as greater than 10 units of product transfused in 24 hours or the incidence of transfusion of greater than three units of product in one hour, otherwise identified as cat 3 plus. The team also compared the transfusion volumes in the emergency department versus over the total length of stay. Pre-hospital vital signs were defined by the nadir heart rate and systolic blood pressures throughout transport and the corresponding shock index with shock being defined as a systolic blood pressure less than or equal to 90 millimeters of mercury. The initiation of pre-hospital low titer O-hole blood transfusion was based on specific previously published criteria. The previously published criteria can be found in an alternative paper, the use of pre-hospital blood products in the resuscitation of trauma patients, a review of pre-hospital transfusion practices, and a description of our regional whole blood program in San Antonio, Texas, published in 2019. The left side of the screen depicts the setup and organization of the regional whole blood program and the right side of the screen, table 2, lists the transfusion criteria in San Antonio for pre-hospital use of low titer O-hole blood. Paramedic guidelines show that whole blood can be administered for patients with systolic blood pressures less than 70 millimeters of mercury or systolic blood pressure less than 90 with a heart rate greater than 110 beats per minute, or an untitled CO2 less than 25, or witness cardiac arrest less than five minutes prior to provider arrival and continuous CPR throughout, downtime or age greater than or equal to 65 years and a systolic blood pressure less than 100 and a heart rate greater than 100 beats per minute. They do list relative contraindications to include patients less than six years old, the need to consult medical direction if a patient is in hemorrhagic shock and less than six years old, the medical director may elect to give blood in patients less than six, and of course for religious objections to receiving whole blood. During the study period, a total of 803 patients who underwent transfusion after hospital arrival were identified with 538 patients remaining for analysis after exclusion of 265 patients due to missing pre-hospital data. Of the 538 patients undergoing transfusion upon arrival, 107 patients received pre-hospital transfusion with 431 patients in the non-transfusion group. The group was further subdivided into those who sustained pre-hospital cardiac arrest totaling 40 and a propensity match group for patients with pre-hospital shock totaling 214 patients of whom 58 received pre-hospital blood transfusion. Table 1 shows the demographics and injury characteristics for all patients undergoing transfusion upon arrival to the trauma bay and reveals that the pre-hospital transfusion group had a higher incidence of male patients, more penetrating trauma, and a lower median ISS or injury severity score. Table 2 depicts the pre-hospital arrival vital signs, mortality, massive transfusion rates, transfusion volumes upon arrival to the emergency department, and length of stay transfusion volumes for all patients on arrival to the trauma bay. Pre-hospital transfusion patients had a lower pre-hospital nadir systolic blood pressure, higher median heart rate, and a higher nadir shock index compared to the non-transfusion patients. The change in shock index depicted as delta SI from nadir to arrival was reduced more significantly in the pre-hospital transfusion group compared to the non-transfusion group. Mortality between the two groups at all time points was not statistically different, however. Although the number of patients in the PHT and NT groups were similar with regard to incidence of massive transfusion, the pre-hospital transfusion group had fewer patients undergoing massive transfusion, defined as greater than 10 units in 24 hours, compared to the non-transfusion group. Overall, pre-hospital transfusion patients required less blood product volume in the emergency department, but ultimately received the same total volume of transfusion over the course of their hospital stay, compared to non-transfusion patients. The pre-hospital transfusion group did receive significantly less pre-hospital crystalloid compared to the non-transfusion group, certainly a benefit of providing whole blood. A propensity matched cohort for patients with pre-hospital shock included a total of 214 patients, 58 of whom received pre-hospital transfusion and 156 who did not. The cohorts were overall similar in demographics and injury characteristics with a similar median injury severity score, similar median age for both groups. The pre-hospital transfusion patients had a higher percentage of male gender and a higher incidence of penetrating trauma, however. The pre-hospital transfusion and non-transfusion patients had similar median major systolic blood pressures, but the PHT group had a higher median heart rate with a trend towards a higher median shock index prior to transfusion. On arrival to the trauma bay, the patients undergoing pre-hospital transfusion had a lower median heart rate, a trend towards a higher median systolic blood pressure, and a greater improvement in median shock index compared to the non- transfusion patients. Overall ED mortality was reduced in the pre-hospital transfusion group with a trend towards lower six-hour mortality. 24-hour mortality and length of stay mortality were similar between both groups. There was no difference in incidence of massive transfusion or cat 3 plus transfusion between the groups. Pre-hospital transfusion patients had an overall lower median volume of blood products transfused in the ED on arrival, but ultimately required a larger transfusion volume over their entire hospital stay compared to the non-transfusion patients. One benefit, however, was that the pre-hospital transfusion group also received a significantly lower volume of crystalloid compared to the non-transfusion group. Despite the limitations of the study, the recent addition of whole blood and trauma resuscitation algorithms has led to the potential for improved survival in civilians. For some of the more severely injured patients, earlier reversal of shock physiology has a potential benefit to improve both short and long-term outcomes. This study illustrates a potential impact of pre-hospital transfusion with low titer O-hole blood in the more severely injured patients with hemorrhagic shock. When examining all of the patients transfused upon arrival, despite their higher degree of shock as defined by lower nadir systolic blood pressure and a higher shock index, those that received pre-hospital transfusion exhibited a greater improvement in shock index upon arrival with a resultant reduction in subsequent massive transfusion. In those patients with the most severe shock physiology in the pre-hospital environment, the pre-hospital transfusion cohort demonstrated an overall reduction in trauma-based mortality and a substantial improvement in shock after a low titer O-hole blood transfusion compared to those who do not receive blood transfusion. Two downsides, however, was that there was no observed benefit in long-term mortality outcomes between the groups and there overall did not appear to be a difference in the incidence of massive transfusion based on whether the patient received transfusion or did not. One major benefit of pre-hospital transfusion with blood products, and in this case low titer O-hole blood, was the overall reduction of the volume of pre-hospital crystalloids administered to the patients. As has been determined, crystalloid administration should really only be used for patients in shock who require additional volume to improve perfusing pressures and not those who are in hemorrhagic shock. The overall limitations of this particular study are that it is retrospective in nature and overall had a small sample size. Analysis of the original data revealed a significant difference between injury severity in the transfused population across the entire service area. The transfusion decision is also a multifactorial one and allows for significant provider discretion and clinical judgment despite having guidelines to follow. And transfusions were also administered to a variety of patients, not those who were deemed to be in shock. Additional limitations of the study include the lack of available transfusion triggers to the pre-hospital providers at the start of the study period prior to the initiation of the pre-hospital low-titer ovo-blood program. As a result, a propensity-matched cohort was necessary to allow for appropriate comparisons. This group, while reflective of severely injured patients, does not reflect the entire cohort of transfused patients who undergo pre-hospital transfusion across the service area. Additionally, a large portion of the original study cohort was excluded based on missing pre-hospital records. Nationally, seen vital signs are defined as vital signs obtained prior to leaving the scene of injury. As would be expected, a large number of patients are initially hemodynamically normal and progress towards shock while en route to the hospital, leading to the use of the nadir systolic blood pressure in this study as it more closely reflects the patient's vital signs at the time of transfusion. Unfortunately, some of these records were not universally available or in some cases were incomplete and thus did not allow for accurate comparisons of these groups, leading to a significant number of exclusions. Despite the limiting factors in this study, the administration of low-titer ovo-blood by our pre-hospital providers showed a greater improvement in shock index and a reduction early mortality in those patients arriving to the trauma bay. Currently, our providers have a limited arsenal of therapies which they can use to help those patients suffering from traumatic injury and specifically hemorrhagic shock and this tool certainly looks like it would be beneficial. Moving forward, however, additional studies will need to be completed, preferably those from a prospective nature involving multiple institutions and multiple EMS jurisdictions. I have listed here additional studies on this topic of pre-hospital blood transfusion that are worthy of your review. I would like to thank you for your undivided attention. I am happy to answer any questions. Please feel free to email me and I would like to give a shout out to my exemplary EMS and critical care transport crew at St. Luke's Emergency and Transport Services. Thank you very much. Have a great day. Hi, my name is Jayna Gardner-Gray. I am an emergency medicine intensivist from Henry Ford Hospital in Detroit, Michigan, and I have no disclosures as far as this lecture. Dr. Peter Safar is described by many as a founding father of critical care medicine here in the U.S. He defined critical care medicine as a triad of, one, resuscitation, two, emergency care for life-threatening conditions, and three, intensive care, and that's including all of the components of the emergency and critical care medicine delivery system, including the pre-hospital and beyond. We think of the ED as a portal of entry for the hospital, and this is the anchor within that continuum. Acknowledging that that triad exists, I'm going to spend the next 15 minutes discussing Time Zero and ICU care on arrival to the ED. I'll review two articles today that are going to go through management in the ED-ICU setting. One of the studies was based in the ED, the other in the ICU, but both pertain to management options in the emergency department. The first article that we're going to discuss today is titled Lung Protective Ventilation and Associated Outcomes and Costs Among Patients Receiving Invasive Mechanical Ventilation in the ED. This was published in CHESS February 2021 by author Dr. Shannon Fernando-Etal. The background of this study involves that invasive mechanical ventilation is often initiated in the emergency department, and this leads to increased demands for ICU beds. Along with limited infrastructure, this can lead to delays in the ICU transfer, increased ED length of stay. Both of these have been shown by recent studies to be associated with adverse outcomes. Additionally, over 250,000 ED patients receive mechanical ventilation annually in the U.S., so it's important to understand how invasive ventilation is used because early ventilation practices may contribute to ventilator-induced lung injury and other ventilator-related complications. So any way we could potentially mitigate those would be very important to know. So there have been many studies highlighting the importance of lung protective strategies in mechanically ventilated patients. The hallmark of lung protective ventilation is the use of low tidal volumes with the goal of reducing the ventilator-induced lung injury. And in the ICU, this is something that's a standard of the care, something that we do fairly routinely because of the improved outcomes that these studies have shown us, particularly those with ARDS, but we've noticed that even in patients without ARDS, there's a benefit to having lower tidal volumes and initiating these lung protective strategies. But these are not as commonly used in the emergency department. In fact, most EDs lack invasive ventilation protocols. So initiation of early lung protective ventilation in the ED, the benefit of this in the ED, I should say, for patients is unclear. However, if lung protective ventilation has been associated with favorable outcomes, this could highlight a field for future quality improvement work in the emergency department. So the research question the authors sought to answer is, what is the association between the use of lung protective ventilation in the ED and outcomes among invasively ventilated patients? So this study was a retrospective analysis of a prospective registry. The EDs that they were looking at had approximately 2,500 total ICU admissions per year, and of these, 1,300 were mechanically ventilated patients. The emergency department breakdown, two were academic tertiary centers and six were community hospitals. And what the study defined as lung protective ventilation was based on tidal volumes of eight cc's per kg of predicted body weight. The primary outcome they looked at was hospital mortality. The secondary outcomes included development of ARDS before hospital discharge or death, duration of invasive ventilation, extubation failure, ICU and hospital length of stay, and total cost for the entire hospital admission. And these included direct and indirect costs. So those direct costs were all the hospital expenses, imaging, laboratory tests, et cetera, and the indirect costs referred to any overhead or operational fees associated with the service provided. So inclusion criteria, adults greater than 18 years of age, you had to have undergone ED mechanical ventilation requiring an ICU admission. Exclusion criteria, if it was non-invasive, BiPAP or high flow nasal cannula, if you had a do not intubate directive, you didn't have data available, or death within 24 hours of the ICU admission. Data was abstracted including demographic, comorbidities, comorbidity index score, multi-organ dysfunction at ICU admission. Additionally, the patient's predicted body weight was recorded at the time of ICU admission. They also collected outcome data from the admission until hospital discharge or hospital death. The ED ventilator settings were taken from the respiratory therapy flow sheets, and the data included with that was ventilator mode, tidal volume, respiratory rate, PEEP, and FIO2. For patients that had multiple tidal volume settings while in the ED, they used the final ventilatory setting prior to ICU transfer. And then they actually did a sub-analysis looking at patients with hypoxemia and patients with ARDS, so two subgroups, which we'll talk about in terms of the results. A total of 4,453 invasively ventilated patients were admitted to the ED to one of the participating ICUs between January 2011 to June 2017. Of these, 4,174 patients were included, and of that, 58.4% or 2,437 received lung protective ventilation while in the ED. No differences were seen between the baseline demographics including age, sex, illness severity, comorbidities, transfer status, prevalence of no CPR directive or the most responsible diagnosis, and the use of lung protective strategies in the ED was associated with lower odds of hospital mortality and reduced incidence of ARDS. Additionally, they saw decreased median duration of mechanical ventilation, ICU length of stay, and hospital length of stay. When they looked at the total cost, they were lower among patients receiving lung protective ventilation as compared to those who did not, and it was a significant predictor of lower cost. This is a five knot restricted cubic spline analysis modeling the association between tidal volume and hospital mortality. If you look at A, this is the entire cohort of mechanically ventilated patients. B is that subgroup of hypoxemic patients, and C are the ED patients with ARDS. And you can see the downward arrows indicate generated knots for specific tidal volumes by predicted body weight. So the analysis identified a substantial inflection point at 8 cc's per kg above which mortality appeared to increase linearly in all of the groups as well as an inflection point at 6 cc's per kg at which the odds of mortality increased again in all groups. So the authors concluded from this study that in patients receiving invasive mechanical ventilation in the ED, one, the use of lung protective strategy was associated with reduced hospital mortality, development of ARDS, duration of invasive ventilation, and total cost. And number two, the use of ED-based protocols for initiation of lung protective ventilation may be beneficial in the care of this patient population. With that being said, there were a lot of limitations in regards to the study. First of all, considering these were retrospective observations done for the data analysis which determines association, not necessarily causation. And then the authors were limited by the data available in their registry. So there was some important data that was not available. And there were ventilator parameters that were not typically measured in the ED, things that we generally look at in the ICU setting including plateau airway pressure, peak inspiratory pressure, and mechanical power. The absence of data can allow for the possibility of confounding, particularly in relation to disease severity, and the P to F ratio was estimated in the study using a linear conversion. Other factors associated with the ED care were not available. For example, if patients received early intervention with antimicrobials for a pulmonary infection or paralysis, we wouldn't know about it. And therefore, the early lung protective ventilation may simply be associated with more timely and appropriate ED care since we did not have that data. We also didn't have the data regarding the duration of invasive ventilation at the initial ED tidal volume settings. It's unclear how the initial ED settings influenced subsequent ventilator settings when that patient was ultimately admitted to the ICU as well. Patients when they left the eight EDs were managed in two separate ICUs. So there is also the possibility of bias related to local practices in those ICUs that the patients were assigned. However, you look at similar protocols that are used in the care of patients for sepsis and DKA and have subsequently been associated with improved patient outcomes. So the use of ED protocols does show promise for a lot of other disease processes. And this study does show a lot of potential favor with implementing these lung protective strategies early on and then being associated with improved patient outcomes. The second study we're going to discuss is the MENDS-2 trial or dexmedetomidine or propofol for sedation of mechanically ventilated adults with sepsis. This was an ICU-based study by Dr. Christopher Hughes et al. and was published in the New England Journal of Medicine. So some of the background, 20 million patients each year have sepsis with organ dysfunction. And of these, over 20% receive mechanical ventilation. We use sedative medications routinely in our patients that are mechanically ventilated for comfort and safety. However, we are aware that some of the medications commonly used for sedation can potentiate brain dysfunction as well as long-term cognitive impairment. Dexmedetomidine is the new but not so new kid on the block that has shown some very favorable properties, specifically in regards to being anti-inflammatory as well as having bacterial clearance properties. These are shown to be superior to benzodiazepines as well as propofol. Some of the basic studies have shown that it reduces neuronal apoptosis and promotes biomimetic sleep, all of which could improve clinical outcomes. Trials comparing dexmedetomidine with benzodiazepines in adults have shown that the use of dexmedetomidine results in improvement in outcomes such as delirium, coma, and time receiving mechanical ventilation. Patients treated with dexmedetomidine had a lower incidence of subsequent infection, and the beneficial effects of dexmedetomidine include lower 28-day mortality, which were more pronounced in patients with sepsis. In comparing dexmedetomidine versus propofol, there was a non-inferiority trial comparing the two in critically ill patients. About half of these patients had sepsis, and it showed that patients who received dexmedetomidine were more interactive, but the choice of sedation did not affect the duration of mechanical ventilation, the length of stay in the ICU or hospital, or short-term mortality. So one treatment was not found to be inferior to the other. So the research question that the authors attempted to answer was, does dexmedetomidine lead to better short- and long-term outcomes than propofol in mechanically ventilated adults with sepsis? So this was a double-blind randomized controlled trial carried out in 13 medical centers in the United States. The primary efficacy endpoint was the number of calendar days alive without delirium or coma during the 14-day intervention period, and the secondary efficacy endpoints were ventilator-free days at that 28 days, death at 90 days, and global cognition at 6 months. The global cognition at 6 months was using the age-adjusted TICS total score. The inclusion criteria were medical or surgical ICU patients with suspected or known infection. They had to have continuous sedation as well as be mechanically ventilated. Exclusion criteria, severe cognitive impairment, pregnant or breastfeeding, blind, deaf, unable to understand approved languages, or a component of bradycardia, whether that be second- or third-degree heart block. Additionally, if the patients received benzodiazepines for extended period time or neuromuscular blockade, then they would be excluded from the study. So the process was pretty straightforward in the fact that dexmedetomidine or propofol were in identical intravenous fluid bags that were covered. The trial drug was initially infused at the same sedative dose that patients were receiving prior to randomization. They all aimed for light sedation, a ROS of 0 to negative 2, in all of the patients. And pain was controlled using the CPOT score, either with intermittent opioid boluses or the fentanyl infusion. Administration of the trial drug was temporarily held in the event of hypotension, bradycardia, if you reached a deeper level of sedation than light sedation, that 0 to 2 of a ROS, and for spontaneous awakening trials or surgery. The trial drug was discontinued after the 14-day intervention period if the patient was extubated, discharged from the ICU, or whichever of these came first. And all centers performed the ABCDE, awakening and breathing coordination, choice of sedation, delirium monitoring and management, and early mobility bundle. In terms of the results, the overall time spent at the target sedation was close to 60% in both groups. Pre-mendazolam was used in about half of the patients. The adjusted number of days alive without delirium or coma over that 14-day intervention period was not significantly different between the two groups. Additionally, there was no significant differences between the dexmedetomidine or propofol groups and the number of ventilator-free days at 28 days. The Kaplan-Meier shown here reflects the survival outcomes and shows that there was no significant difference between the trial groups with respect to death at 90 days. And there was no significant difference in long-term cognitive impairment at the six-month follow-up. Safety endpoints were also similar in both of the groups. The authors of the study concluded that they did not find evidence that sedation with dexmedetomidine led to, one, more days alive without acute brain dysfunction than propofol, or two, ventilator-free days at 28 days, death at 90 days, or global cognition at six months. So despite the theoretical benefits we discussed before, the anti-inflammatory and antibacterial studies supporting the use of dexmedetomidine, the choice between dexmedetomidine and propofol alone does not appear to substantially affect patient outcomes in critical illness with sepsis. So the authors ultimately reinforced the current guidelines recommending the use of either dexmedetomidine or propofol for late sedation when continuous sedation is needed for adults with or without sepsis who are on mechanical ventilation. One limitation to be noted is that unmasking episodes happen in 14% of patients and crossover in about 10% of the patients. There also was a cross-contamination with other sedatives, though this has shown to be less than in other sedation studies that have been conducted. The highlights from these two articles are, one, the use of ED-based protocols for initiation of lung protective ventilation may be beneficial in the care of our ED-ventilated patients, and two, there does not seem to be short or long-term benefit in using dexmedetomidine over propofol for sedation in mechanically ventilated patients. Thank you for listening in and for attending this session. Good afternoon. It's Chris Greal joining you for the third and final portion of EMCCM 2021 in review. I'd like to begin by discussing TTM2. This study was published in New England Journal of Medicine in February of 2021. It's an international multi-centered randomized superiority trial consisting of 14 countries and enrollment period from 2017 to 2020. Purpose of this study was to evaluate outcomes related to adherence to a strict hypothermia protocol versus normothermia. Adults age 18 or older that sustained a cardiac arrest outside of the hospital and demonstrated 20 minutes of sustained ROS time were included in this study. Early researchers evaluated or obtained a four-score full outline of unresponsiveness scale. A scale that doesn't depend on verbal response, but instead looks at ocular motor responses, respiratory patterns, and brainstem reflexes. Exclusion criteria included those that sustained an asystolic or unwitnessed arrest, were 180 minutes or greater from ROS to screening time, or were notably cannulated for ECMO, pregnant, or profoundly hypothermic on arrival and presentation. Researchers wanted to evaluate mortality at six months and functional impairment at six months as well. Functional impairment was defined by a modified Rankin score, namely score of four to six. So amidst the 4,000-plus patients that were screened in 1900 that were randomized, there were two groups of 930 and 931 in the hypothermia and normothermia group, respectively. On evaluation of outcomes, there was no difference in all-cause mortality at six months comparing the normothermia and hypothermia groups. On functional status evaluation and self-reporting levels of health-related quality of life, there was additionally no difference amongst the groups. Adverse events rate were also looked at. Those were similar within the two groups with respect to arrhythmias. There was an increased significance and incidence of that in the hypothermia group compared to the normothermia group. There was a subgroup analysis examining the role of gender, age, time to ROS, initial rhythm and shock present that is listed there and essentially resulted in the same findings. So with this slide and others in the future, I'd like to take a moment both to applaud and congratulate the authors of each study prior to transitioning to discuss some limitations and consideration of applicability and generalizability and overall look at the study in the scope of existing evidence-based literature. So firstly, I'd like to applaud and congratulate the authors of this study on their sound methodology and their solid primary outcomes as well as their attempts to blind or have blind evaluation whenever possible in a study as challenging as this. It was a well-balanced study amongst the two groups. There was a notable male predominance. Limitations included the fact that this was an outside hospital study population only. When we start looking at generalizability and overall implications, there were a moderate amount of devices that were required to avoid fever, about 46% of patients in the normothermia group did require a device. So when looking at cost implications, something to note. Overall the role of the cooling timeline has continued to be a discussion circulating TTM and definitely coming into play in this trial as the majority of patients were cooled within an eight-hour period, causing some to wonder and question the effect of this and this timeline on outcomes. When discussing considerations and kind of reviewing applicability and generalizability, I'd definitely be remiss if I didn't mention some of the distinct population characteristics of the subjects within this trial when we compare those to other studies that have previously reported a signal for not just benefit and quote avoiding fever, but in true TTM. So this population had a 92% witnessed arrest rate, 78% of these patients received bystander CPR, 30% or more, 30% excuse me, or less had shock on presentation or arrival, and the majority of patients had shockable rhythms with a 40% STEMI incidence rate. Now overall review of this study left me inspired to not just review existing trials and evaluate the concept of risk stratification in my post-arrest patients, but it additionally made me excited to review some of the results from upcoming clinical trials that are investigating the role of cooling timeline and associated outcomes such as ice cap. So amidst cardiopulmonary resuscitation ultrasound has demonstrated a pretty significant merit with respect to just visualization directly of cardiac motion, standstill, and overall identification of actionables, reversible etiologies, et cetera. This next study that I wanted to discuss examined the role of echo and ultrasound in post-arrest care diagnostics management and then looked at an association with some longitudinal outcomes. So the purpose of this study was to evaluate LV systolic dysfunction, which was described as an LVEF of less than 40 on echo, and also look at the presence of regional wall abnormalities. They additionally looked at a couple of different other outcomes, incidence rates of cardiogenic shock, CAD, and complexity of cardiovascular disease. Adult patients sustaining outside hospital arrest with a subsequent ROSC who received both an echo and heart cath were included in this study. Exclusion criteria is as listed. Researchers wanted to look at mortality at 12 months as well as at 30 days and then neurologic outcomes at six months, mode of death at 12 months, and again, incidence rates of cardiogenic shock and CAD as I mentioned previously. Amidst the 266 patients included, the predominance of this subject group were male, about 74%, with an average age of 64 and LVEF of 41%. There was a notably short zero and low flow time. A predominance of shockable rhythm and incidence of STEMI, bundle branch, or ischemic changes were present in about 61% of this population. Upon delving into the specific subgroups, looking at those with LV dysfunction or regional wall abnormalities, the LV dysfunction group was notably found to have more common longer durations of low flow time, increased metabolic derangements and acidemia, and then higher rates of cardiogenic shock and complex CAD. The regional wall motion abnormality group, on the other hand, had shorter total or low flow down times, more favorable metabolic profiles, and were more likely to have STEMI and culprit regions, less likely to have shock. On evaluation of outcomes, there were two pervasive groups that continued to stick out and were associated with having worse longitudinal outcomes. The first was mortality at 12 months, and when looking at that, and then subsequently looking at neurologic outcomes, cardiogenic modes of death, et cetera, the two groups that did the worst historically were those with a reduced ejection fraction less than 40, and those without the presence of regional wall abnormalities. Now upon evaluation of mode of death at 12 months, researchers wanted to look specifically at cardiogenic motor etiology. The group that was highest risk for this mode of death at 12 months were those with a reduced ejection fraction. This is an additional pictorial representation of outcomes. If you notice the flow chart on the left, it's a different visual presentation, but allows for kind of mental grouping and risk categorization stratification, again, demonstrating the best prognostic being a preserved EF on echo, and then within the subgroups of reduced and greater than 40, not truly preserved, but greater than 40% LVEF, having the best survival within those subgroups was associated with the presence of regional wall abnormalities, and as you saw, that highly correlated with the presence of a culprit region. So applause for the authors for this novel concept, and again, their utilization of pre-hospital database, their ability to communicate with the London Ambulance Service ensured that we had the amount of detailed information and accurate information that was provided in this trial. When discussing limitations with respect to generalizability and causation, this was a single-centered study, had a very specific population, and a pretty impressive cardiology availability, namely being able to perform an echo at bedside within 30 minutes of arrival. Again, when delving into the literature associated with this topic, I found myself, again, looking and thinking of how to assimilate these findings with that of DISCO and COACT and the Tomahawk trials when assessing angiographic timeline. I think overall it re-demonstrated to me at least the importance of the inclusion of echo in my algorithm of continued clinical and echocardiographic assessment of my patients post-ROSC. And honestly, with the expanding role of bedside, ultrasound, and TEE, although this is a small single-centered study, I have no doubt that some of the additional clinical questions that were raised by this study will continue to be explored, undoubtedly, in the future. So kind of continuing in this concept of incorporating new and existing evidence in a manner that allows us to better care for patients, I wanted to focus on a topic that is near and dear to our specialty, both personally and professionally, nutrition and food. So this publication was in Critical Care Medicine in January of 2021. It's a retrospective observational study with a pretty robust subject population in varied center geography and locations with respect to contributors to the study. And that's a result of it being obtained by an analysis of an international database or this international nutritional survey. The purpose of this study, they wanted to not just determine the incidence of enteral feeding intolerance, but also to look at some of the factors that were associated with that and then further delve into relationship between feeding intolerance and clinical outcomes. So adults that were ventilated for greater than 48 hours had been in the ICU for greater than 12 hours and received enteral nutrition within 12 days of ICU admission were included in this study. Some of the outcomes that they looked at included not just incidence and risk factors, like I mentioned, but in-hospital mortality, ICU and hospital length of stay, and ventilator-free days. So this was a large and multi-centered population, not just that it was a pretty nice mix of medical and surgical patients and ICU indications for admissions. Upon looking at outcomes, overall rate of enteral feeding intolerance was approximately 24%. It peaked on ICU day four to five and did have an increasing association with high Apache scores and a predominance in patients with burn, sepsis, or a GI indication for admission as opposed to like a metabolic or neurologic-based pathology indicating their admission to ICU. Other outcomes that they looked at when looking at protein and caloric goals being met, they found that there was decreased or reduced meeting of goals in patients that had feeding intolerance. There was also ventilator-free days were reduced also in this group. Upon looking at ICU length of stay and time to discharge, both of these were increased in duration in those that had documented enteral feeding intolerance. So again, there are some limitations in this study. The design is retrospective and observational, and it's obviously difficult to ascertain causation as a result of this. When looking at applicability, the variety of medical and surgical patients and diverse patient population and ability to get this data is something that I definitely applaud researchers for. As I reviewed this and kind of considered some of the controversy existing and surrounding gastric residual volumes and assessing those volumes, and then some skepticism with respect to how important is reduced caloric intake and what timeline is this clinically important and how does this translate into patient outcomes, I did find that some value in existing, kind of incorporating this existing data with respect to nutritional assessment, so not just scoring but multifactorial assessment of intolerance, risk for intolerance, profiles that would have more risk for malnutrition in the ICU, etc. I mean, overall, inarguably, consistent and appropriate nutrition in the ICU is incredibly important for all critically ill patients. Now how to best stratify those at risk early on prior to the development of clinical evidence of intolerance definitely is going to warrant further exploration, but it's also evidence for continued need for, how shall we say, the art behind medicine and the value of a multifactorial assessment and considerations guiding our management. The last thing, I would be remiss if I didn't at least bring one publication related to the pandemic that has left us forever changed. Being that the majority of us, myself included, are likely saturated with this topic, I did want to spend a moment discussing something that I think has not only expanded during this pandemic but has practical implications that I believe will continue to exponentially grow and be seen in the future. So I want to review the ALSO 2021 guidelines for utilization of ECMO in COVID-19. Now the purpose of this review was to kind of discuss the expanding role of ECMO, namely VV-ECMO for ARDS in the context of the COVID-19 pandemic, but as I mentioned, the implications for utilization of VV-ECMO in ARDS I think will continue to be there and this is a technology that has continued to boom and expand, so as we learn more about it, it's worth at least discussing or mentioning that this publication is out there. I think there were some notables and, you know, principles in consideration with respect to management prior to ECMO initiation, being that ECMO management or the management of patients on ECMO is relatively unchanged intra-pandemic compared to pre-pandemic data. The only difference that we're seeing or the predominant difference that we're seeing is a longer duration of support requirements in patients with ARDS secondary to COVID. Now when talking about considerations for patient management prior to ECMO, conventional management principles are the same. You know, advocacy of pronation, low pressure, low volume, ventilation, consideration neuromuscular blockade, all those principles hold. Now the rule for early transfer and referral, whether that's in anticipation of deterioration or at the first signs of inability to safely mechanically ventilate a patient, these are things worth considering when caring for these patients potentially at a center that is not an ECMO center. Other things to consider are overall duration of invasive mechanical support in history and compromising conditions, whether that's degree of comorbidities, life expectancy, advanced age, immunocompromised state. These are all things that ECMO consultants in an ECMO center will be evaluating but add to the complexity of these decisions, particularly in a time of limited resources and a pandemic. Also long-term options and bridging in therapy and some of the gray zones associated with management of patients on ECMO with very long duration of support requirements and those that don't have an option to bridge to transplant because they aren't candidacy or don't meet candidacy for transplantation. These are some of these gray zones that require some thought and consideration when having these initial conversations that I think are worth mentioning. So concepts that are being currently further explored in this patient subset and I hope will continue both at our center and at other ECMO centers include the concept of pronation, not just limited to patients off ECMO or pre-ECMO, but those on ECMO that meet indication or show that they might have demonstrable benefit for this. The concept of mechanical liberation from the ventilator. So early extubation, why keep a patient intubated when we can lighten their sedation, ameliorate their inaugural sedation requirements, allow them to progress to eating and phonating independently while they are awake and walking and rehabilitating early. Cannula configuration is something that additionally has continued to expand and grow, whether that's the initial configuration strategies and evaluation of reconfiguring cannulation strategies and the setting of recovery and weaning and some of these longer supports. But utilization of delumine cannulas, VVV strategies, RVAD type devices, it's been really interesting to see kind of applications of this in this population and what this will bring us in the future. So the primary sources are cited at the top of this and I have some secondary citations and references available on request. Thank you for your time.

cardiac arrest

hypothermia treatment

echocardiography

enteral feeding intolerance

ICU stays

ECMO utilization

COVID-19

conventional management

bridging therapy

Emergency Medicine and EMS Care