Good afternoon, it's Chris Creel 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. The purpose of this study was to evaluate outcomes related to adherence to a strict hypothermia protocol versus normothermia. Adults aged 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. Additionally, 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 a hundred and eighty 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 rank and 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 the expect 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 in, 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 in 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 prehospital 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 a 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. 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 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, 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, 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 into 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 delumen 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.

TTM2 study

hypothermia protocol

normothermia

cardiac arrest

mortality

Emergency Medicine and EMS Care