Reducing the burden of acute respiratory distress syndrome: The case for early intervention and the potential role of the emergency department

The mortality for acute respiratory distress syndrome (ARDS) remains unacceptably high. Success in clinical trials has been limited, resulting in a lack of effective therapies to treat the syndrome. The projected increase in mechanically ventilated patients and global need for critical care services suggests that the clinical and research landscape in ARDS can no longer be confined to the intensive care unit (ICU). A demonstrable minority of patients present to the emergency department (ED) with ARDS, and ARDS onset typically occurs shortly after ICU admission. Furthermore, the ED is an entry point for many of the highest risk patients for ARDS development and progression. These facts, combined with prolonged lengths of stay in the ED, suggest that the ED could represent a window of opportunity for treatment and preventive strategies, as well as clinical trial enrollment. This review aims to discuss some of the potential strategies which may prevent or alter the trajectory of ARDS, with a focus on the potential role the ED could play in reducing the burden of this syndrome

Emergency department hyperoxia is associated with increased mortality in mechanically ventilated patients: A cohort study

Definitions of comorbid conditions. (DOCX 13 kb

Lower tidal volume at initiation of mechanical ventilation may reduce progression to acute respiratory distress syndrome: A systematic review

INTRODUCTION: The most appropriate tidal volume in patients without acute respiratory distress syndrome (ARDS) is controversial and has not been rigorously examined. Our objective was to determine whether a mechanical ventilation strategy using lower tidal volume is associated with a decreased incidence of progression to ARDS when compared with a higher tidal volume strategy. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, the Cochrane Library, conference proceedings, and clinical trial registration was performed with a comprehensive strategy. Studies providing information on mechanically ventilated patients without ARDS at the time of initiation of mechanical ventilation, and in which tidal volume was independently studied as a predictor variable for outcome, were included. The primary outcome was progression to ARDS. RESULTS: The search yielded 1,704 studies, of which 13 were included in the final analysis. One randomized controlled trial was found; the remaining 12 studies were observational. The patient cohorts were significantly heterogeneous in composition and baseline risk for developing ARDS; therefore, a meta-analysis of the data was not performed. The majority of the studies (n = 8) showed a decrease in progression to ARDS with a lower tidal volume strategy. ARDS developed early in the course of illness (5 hours to 3.7 days). The development of ARDS was associated with increased mortality, lengths of stay, mechanical ventilation duration, and nonpulmonary organ failure. CONCLUSIONS: In mechanically ventilated patients without ARDS at the time of endotracheal intubation, the majority of data favors lower tidal volume to reduce progression to ARDS. However, due to significant heterogeneity in the data, no definitive recommendations can be made. Further randomized controlled trials examining the role of lower tidal volumes in patients without ARDS, controlling for ARDS risk, are needed. 2013 Fuller et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Importance of decision support implementation in emergency department vancomycin dosing

INTRODUCTION: The emergency department (ED) plays a critical role in the management of life-threatening infection. Prior data suggest that ED vancomycin dosing is frequently inappropriate. The objective is to assess the impact of an electronic medical record (EMR) intervention designed to improve vancomycin dosing accuracy, on vancomycin dosing and clinical outcomes in critically ill ED patients. METHODS: Retrospective before-after cohort study of all patients (n=278) treated with vancomycin in a 60,000-visit Midwestern academic ED (March 2008 and April 2011) and admitted to an intensive care unit. The primary outcome was the proportion of vancomycin doses defined as “appropriate” based on recorded actual body weight. We also evaluated secondary outcomes of mortality and length of stay. RESULTS: The EMR dose calculation tool was associated with an increase in mean vancomycin dose ([14.1±5.0] vs. [16.5±5.7] mg/kg, p<0.001) and a 10.3% absolute improvement in first-dose appropriateness (34.3% vs. 24.0%, p=0.07). After controlling for age, gender, methicillin-resistant staphylococcus aureus infection, and Acute Physiology and Chronic Health Evaluation II score, 28-day in-hospital mortality (odds ratio OR 1.72; 95% CI [0.76–3.88], p=0.12) was not affected. CONCLUSION: A computerized decision-support tool is associated with an increase in mean vancomycin dose in critically ill ED patients, but not with a statistically significant increase in therapeutic vancomycin doses. The impact of decision-support tools should be further explored to optimize compliance with accepted antibiotic guidelines and to potentially affect clinical outcome

Lung-protective ventilation initiated in the emergency department (LOV-ED): A study protocol for a quasi-experimental, before-after trial aimed at reducing pulmonary complications

INTRODUCTION: In critically ill patients, acute respiratory distress syndrome (ARDS) and ventilator-associated conditions (VACs) are associated with increased mortality, survivor morbidity and healthcare resource utilisation. Studies conclusively demonstrate that initial ventilator settings in patients with ARDS, and at risk for it, impact outcome. No studies have been conducted in the emergency department (ED) to determine if lung-protective ventilation in patients at risk for ARDS can reduce its incidence. Since the ED is the entry point to the intensive care unit for hundreds of thousands of mechanically ventilated patients annually in the USA, this represents a knowledge gap in this arena. A lung-protective ventilation strategy was instituted in our ED in 2014. It aims to address the parameters in need of quality improvement, as demonstrated by our previous research: (1) prevention of volutrauma; (2) appropriate positive end-expiratory pressure setting; (3) prevention of hyperoxia; and (4) aspiration precautions. METHODS AND ANALYSIS: The lung-protective ventilation initiated in the emergency department (LOV-ED) trial is a single-centre, quasi-experimental before-after study testing the hypothesis that lung-protective ventilation, initiated in the ED, is associated with reduced pulmonary complications. An intervention cohort of 513 mechanically ventilated adult ED patients will be compared with over 1000 preintervention control patients. The primary outcome is a composite outcome of pulmonary complications after admission (ARDS and VACs). Multivariable logistic regression with propensity score adjustment will test the hypothesis that ED lung-protective ventilation decreases the incidence of pulmonary complications. ETHICS AND DISSEMINATION: Approval of the study was obtained prior to data collection on the first patient. As the study is a before-after observational study, examining the effect of treatment changes over time, it is being conducted with waiver of informed consent. This work will be disseminated by publication of full-length manuscripts, presentation in abstract form at major scientific meetings and data sharing with other investigators through academically established means. TRIAL REGISTRATION NUMBER: NCT02543554

A dual-center cohort study on the association between early deep sedation and clinical outcomes in mechanically ventilated patients during the COVID-19 pandemic: The COVID-SED study

BACKGROUND: Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes. STUDY DESIGN AND METHODS: Dual-center, retrospective cohort study conducted over 6 months (March-August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 h were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of - 3 to - 5 or Riker Sedation-Agitation Scale of 1-3. To examine impact of early sedation depth on hospital mortality (primary outcome), we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days. RESULTS: 391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation (p \u3c 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65-7.17; p \u3c 0.01). These results were stable in the subgroup of patients with COVID-19. CONCLUSIONS: The management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach

A study protocol for a multicentre, prospective, before-and-after trial evaluating the feasibility of implementing targeted SEDation after initiation of mechanical ventilation in the emergency department (The ED-SED Pilot Trial)

INTRODUCTION: Sedation is a cornerstone therapy in the management of patients receiving mechanical ventilation and is highly influential on outcome. Early sedation depth appears especially influential, as early deep sedation is associated with worse outcome when compared with light sedation. Our research group has shown that patients receiving mechanical ventilation in the emergency department (ED) are exposed to deep sedation commonly, and ED sedation depth is impactful on intensive care unit (ICU) care and clinical outcomes. While extensive investigation has occurred for patients in the ICU, comparatively little data exist from the ED. Given the influence that ED sedation seems to carry, as well as a lack of ED-based sedation trials, there is significant rationale to investigate ED-based sedation as a means to improve outcome. METHODS AND ANALYSIS: This is a multicentre (n=3) prospective, before-and-after pilot trial examining the feasibility of implementing targeted sedation in the immediate postintubation period in the ED. A cohort of 344 patients receiving mechanical ventilation in ED will be included. Feasibility outcomes include: (1) participant recruitment; (2) proportion of Richmond Agitation-Sedation Scale (RASS) scores in the deep sedation range; (3) reliability (agreement) of RASS measurements performed by bedside ED nurses; and (4) adverse events. The proportion of deep sedation measurements before and after the intervention will be compared using the χ ETHICS AND DISSEMINATION: The Human Research Protection Office at Washington University in St. Louis School of Medicine has approved the study. The publication of peer-reviewed manuscripts and the presentation of abstracts at scientific meetings will be used to disseminate the work. REGISTRATION: ClinicalTrials.gov identifier NCT04410783; Pre-results

Awareness with paralysis and symptoms of post-traumatic stress disorder among mechanically ventilated emergency department survivors (ED-AWARENESS-2 Trial): study protocol for a pragmatic, multicenter, stepped wedge cluster randomized trial.

BACKGROUND: Awareness with paralysis (AWP) is memory recall during neuromuscular blockade (NMB) and can cause significant psychological harm. Decades of effort and rigorous trials have been conducted to prevent AWP in the operating room, where prevalence is 0.1-0.2%. By contrast, AWP in mechanically ventilated emergency department (ED) patients is common, with estimated prevalence of 3.3-7.4% among survivors given NMB. Longer-acting NMB use is a critical risk for AWP, and we have shown an association between ED rocuronium use and increased AWP prevalence. As NMB are given to more than 90% of ED patients during tracheal intubation, this trial provides a platform to test an intervention aimed at reducing AWP. The overall objective is to test the hypothesis that limiting ED rocuronium exposure will significantly reduce the proportion of patients experiencing AWP. METHODS: This is a pragmatic, stepped wedge cluster randomized trial conducted in five academic EDs, and will enroll 3090 patients. Per the design, all sites begin in a control phase, under observational conditions. At 6-month intervals, sites sequentially enter a 2-month transition phase, during which we will implement the multifaceted intervention, which will rely on use of nudges and defaults to change clinician decisions regarding ED NMB use. During the intervention phase, succinylcholine will be the default NMB over rocuronium. The primary outcome is AWP, assessed with the modified Brice questionnaire, adjudicated by three independent, blinded experts. The secondary outcome is the proportion of patients developing clinically significant symptoms of post-traumatic stress disorder at 30 and 180 days after hospital discharge. We will also assess for symptoms of depression and anxiety, and health-related quality of life. A generalized linear model, adjusted for time and cluster interactions, will be used to compare AWP in control versus intervention phases, analyzed by intention-to-treat. DISCUSSION: The ED-AWARENESS-2 Trial will be the first ED-based trial aimed at preventing AWP, a critical threat to patient safety. Results could shape clinical use of NMB in the ED and prevent more than 10,000 annual cases of AWP related to ED care. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05534243 . Registered 06, September 2022

Protocol for a prospective, observational cohort study of awareness in mechanically ventilated patients admitted from the emergency department: The ED-AWARENESS study

INTRODUCTION: Awareness with paralysis is a complication with potentially devastating psychological consequences for mechanically ventilated patients. While rigorous investigation into awareness has occurred for operating room patients, little attention has been paid outside of this domain. Mechanically ventilated patients in the emergency department (ED) have been historically managed in a way that predisposes them to awareness events: high incidence of neuromuscular blockade use, underdosing of analgesia and sedation, delayed administration of analgesia and sedation after intubation, and a lack of monitoring of sedation targets and depth. These practice patterns are discordant to recommendations for reducing the incidence of awareness, suggesting there is significant rationale to examine awareness in the ED population. METHODS AND ANALYSIS: This is a single centre, prospective cohort study examining the incidence of awareness in mechanically ventilated ED patients. A cohort of 383 mechanically ventilated ED patients will be included. The primary outcome is awareness with paralysis. Qualitative reports of all awareness events will be provided. Recognising the potential problem with conventional multivariable analysis arising from a small number of events (expected less than 10-phenomenon of separation), Firth penalised method, exact logistic regression model or penalised maximum likelihood estimation shrinkage (Ridge, LASSO) will be used to assess for predictors of awareness. ETHICS AND DISSEMINATION: Approval of the study by the Human Research Protection Office has been obtained. This work will be disseminated by publication of peer-reviewed manuscripts, presentation in abstract form at scientific meetings and data sharing with other investigators through academically established means