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 author 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 eight cc's per kg above which mortality appeared to increase linearly in all of the groups as well as an inflection point at six 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 that 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 them 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 of 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 opiate 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. The human dazolam 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 happened 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.

ICU care

emergency department

lung protective ventilation

mechanically ventilated patients

sedation

Emergency Medicine and EMS Care