Partial pressure of carbon dioxide/pH interaction and its association with mortality among patients mechanically ventilated in the emergency department.

OBJECTIVES: There is currently conflicting data as to the effects of hypercapnia on clinical outcomes among mechanically ventilated patients in the emergency department (ED). These conflicting results may be explained by the degree of acidosis. We sought to test the hypothesis that hypercapnia is associated with increased in-hospital mortality and decreased ventilator-free days at lower pH, but associated with decreased in-hospital mortality and increased ventilator-free days at higher pH, among patients requiring mechanical ventilation in the emergency department (ED). METHODS: Secondary analysis of patient level data from prior clinical trials and cohort studies that enrolled adult patients who required mechanical ventilation in the ED. Patients who had a documented blood gas while on mechanical ventilation in the ED were included in these analyses. The primary outcome was in-hospital mortality, and secondary outcome was ventilator-free days. Mixed-effects logistic, linear, and survival-time regression models were used to test if pH modified the association between partial pressure of carbon dioxide (pCO2) and outcome measures. RESULTS: Of the 2348 subjects included, the median [interquartile range (IQR)] pCO2 was 43 (35-54) and pH was 7.31 (7.22-7.39). Overall, in-hospital mortality was 27%. We found pH modified the association between pCO2 and outcomes, with higher pCO2 associated with increased probability of in-hospital mortality when pH is below 7.00, and decreased probability of in-hospital mortality when pH is above 7.10. These results remained consistent across multiple sensitivity and subgroup analyses. A similar relationship was found with ventilator-free days. CONCLUSIONS: Higher pCO2 is associated with decreased mortality and greater ventilator-free days when pH is >7.10; however, it is associated with increased mortality and fewer ventilator-free days when the pH is below 7.00. Targeting pCO2 based on pH in the ED may be a potential intervention target for future clinical trials to improve clinical outcomes.

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.

Benzonatate Overdose Presenting as Cardiac Arrest with Rapidly Narrowing QRS Interval.

INTRODUCTION: Benzonatate is a local anesthetic-like sodium channel antagonist that is widely prescribed as an antitussive. While it may be reasonable to assume that patients would present with a prolonged QRS interval following benzonatate overdose, the published literature does not support this. We report a case of a patient presenting following a benzonatate overdose with a prolonged QRS on her initial electrocardiograph (ECG) rhythm strip with rapid normalization of QRS duration. CASE REPORT: A 14-year-old girl presented in cardiac arrest following a benzonatate overdose. The patient was found in cardiac arrest within minutes of last being known well. Bystanders immediately provided cardiopulmonary resuscitation (CPR), and she was in asystole on emergency medical services (EMS) arrival. Return of spontaneous circulation (ROSC) was obtained following administration of intraosseous epinephrine and naloxone. EMS obtained an ECG rhythm strip following ROSC demonstrating a sinus rhythm with a QRS duration of 160 ms. Over the ensuing 30 minutes, there was progressive narrowing of the QRS. A 12-lead ECG obtained on arrival in the emergency department (ED) 44 minutes later demonstrated a QRS duration of 94 ms. Initially, EMS ECG rhythm strips were unavailable and an isolated benzonatate ingestion was considered less likely as ECG intervals were normal. Benzonatate exposure was later confirmed with a urine benzonatate concentration, which was 8.5 mcg/mL. The patient made a full recovery. DISCUSSION: Cases of pediatric benzonatate overdose with rapid development of cardiac arrest and full recovery have been previously reported. In this case, evidence of cardiac sodium channel blockade was demonstrated with a prolonged QRS interval on initial ECG rhythm strip analysis. However, unlike previous cases, rapid resolution of QRS prolongation occurred in this case. While transient QRS prolongation may be observed, finding a normal QRS interval should not discount the possibility of benzonatate overdose.

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 < 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 < 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.

The Feasibility of Implementing Targeted SEDation in Mechanically Ventilated Emergency Department Patients: The ED-SED Pilot Trial.

OBJECTIVES: Deep sedation in the emergency department (ED) is common, increases deep sedation in the ICU, and is negatively associated with outcome. Limiting ED deep sedation may, therefore, be a high-yield intervention to improve outcome. However, the feasibility of conducting an adequately powered ED-based clinical sedation trial is unknown. Our objectives were to assess trial feasibility in terms of: 1) recruitment, 2) protocol implementation and practice change, and 3) safety. Patient-centered clinical outcomes were assessed to better plan for a future large-scale clinical trial. DESIGN: Pragmatic, multicenter ( n = 3), prospective before-after pilot and feasibility trial. SETTING: The ED and ICUs at three medical centers. PATIENTS: Consecutive, adult mechanically ventilation ED patients. INTERVENTIONS: An educational initiative aimed at reliable ED sedation depth documentation and reducing the proportion of deeply sedated patients (primary outcome). MEASUREMENTS AND MAIN RESULTS: Sedation-related data in the ED and the first 48 ICU hours were recorded. Deep sedation was defined as a Richmond Agitation-Sedation Scale of -3 to -5 or a Sedation-Agitation Scale of 1-3. One thousand three hundred fifty-six patients were screened; 415 comprised the final population. Lighter ED sedation was achieved in the intervention group, and the proportion of deeply sedated patients was reduced from 60.2% to 38.8% ( p < 0.01). There were no concerning trends in adverse events (i.e., inadvertent extubation, device removal, and awareness with paralysis). Mortality was 10.0% in the intervention group and 20.4% in the preintervention group ( p < 0.01). Compared with preintervention, the intervention group experienced more ventilator-free days [22.0 (9.0) vs 19.9 (10.6)] and ICU-free days [20.8 (8.7) vs 18.1 (10.4)], p < 0.05 for both. CONCLUSIONS: This pilot trial confirmed the feasibility of targeting the ED in order to improve sedation practices and reduce deep sedation. These findings justify an appropriately powered clinical trial regarding ED-based sedation to improve clinical outcomes.

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 six months (March - August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 hours 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 < 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 <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. Clinical Trial Registration : Not applicable.

Awareness With Paralysis in Mechanically Ventilated Patients in the Emergency Department and ICU: A Systematic Review and Meta-Analysis.

OBJECTIVE: Awareness with paralysis is a devastating complication for mechanically ventilated patients and can carry long-term psychologic sequelae. Hundreds of thousands of patients require mechanical ventilation in the emergency department and ICU annually, yet awareness has only been rigorously examined in the operating room (incidence ~0.1%). This report collates the global literature regarding the incidence of awareness with paralysis outside of the operating room. DATA SOURCES: We searched OvidMedline, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, conference proceedings, and reference lists. STUDY SELECTION: Randomized or nonrandomized studies (except single case studies) reporting on awareness with paralysis in the emergency department or ICU were eligible. DATA EXTRACTION: Two independent reviewers screened abstracts for eligibility. DATA SYNTHESIS: The search identified 4,454 potentially eligible studies. Seven studies (n = 941 patients) were included for analysis. A random effects meta-analysis of proportions along with multiple subgroup analyses was performed. Significant between-study heterogeneity in reporting of awareness with paralysis was noted, and the quality of the evidence was low. Analyses stratified by: 1) good-quality studies and 2) use of the modified Brice questionnaire to detect awareness revealed estimates of 3.4% (95% CI, 0-10.2%) and 1.9% (95% CI, 1.0-3.0%), respectively. CONCLUSIONS: The incidence of awareness with paralysis in mechanically ventilated patients in the emergency department and ICU, as evaluated in a small number of qualifying studies from this comprehensive systematic review, appears much higher than that reported from the operating room. Given the clinical and statistical heterogeneity, caution is warranted in the interpretation of these findings. Further high-quality studies are needed to both define the true incidence and to target the prevention of awareness with paralysis in this vulnerable patient cohort.

Central Nervous System Infections in the Immunocompromised Adult Presenting to the Emergency Department.

Over the past 2 decades, the population of immunocompromised patients has increased dramatically in the United States. These patients are at elevated risk for both community-acquired and opportunistic central nervous system infections. We review the most common and serious central nervous system pathogens affecting these patients and outline a diagnostic and therapeutic approach to their management in the emergency department. We recommend a broad diagnostic evaluation, including neuroimaging and cerebrospinal fluid studies where appropriate, empiric antimicrobial therapy, and early involvement of subspecialists to provide comprehensive care for these complex patients.

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 χ2 test. Logistic regression will be used to compare before-and-after differences, adjusting for potential confounders. The inter-rater correlation coefficient will be used to assess paired observations between a study team member and bedside ED nurses, and to describe reliability of RASS measurements. 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 and bispectral index (BIS) monitoring in mechanically ventilated patients in the emergency department and intensive care unit: a systematic review protocol.

INTRODUCTION: Accidental awareness with recall is one of the most feared complications for patients undergoing general anaesthesia and can lead to post-traumatic stress disorder in up to 70% of patients experiencing it. To reduce the incidence of awareness with recall, the bispectral index monitor is recommended for patients receiving total intravenous anaesthetics, especially those receiving neuromuscular blockers. While extensive investigation into awareness and bispectral index monitoring has occurred for operating room patients, this has not extended to other clinical arenas where sedated and mechanically ventilated patients are cared for, namely the intensive care unit and emergency department. The purpose of this systematic review is to assess the world's literature to determine the incidence of awareness with paralysis in mechanically ventilated patients and the impact of bispectral index monitoring for reducing this complication. METHODS AND ANALYSIS: Randomised trials and non-randomised studies are eligible for inclusion. With aid from a medical librarian, an electronic search will include Ovid Medline, Embase.com, Scopus, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials. To find data published in abstract form, literature from professional society conferences (2010-2019) will be manually searched. Two authors will independently review search results and consensus will be reached with assistance from a third author, as needed. Heterogeneity and publication bias will be assessed and reported. If possible and appropriate, a meta-analysis of the data will be conducted for quantitative data analysis. ETHICS AND DISSEMINATION: The proposed systematic review does not require ethical approval, as it is conducted at the study level and does not involve individual patient-level data. Results will be disseminated by data sharing via academically established means, presentation at local and national scientific meetings and publication as a peer-reviewed manuscript. PROSPERO REGISTRATION NUMBER: The protocol has been submitted to International Prospective Register of Systematic Reviews and is awaiting registration.

Ketamine sedation in mechanically ventilated patients: A systematic review and meta-analysis.

PURPOSE: Ketamine use as a sedative agent in mechanically ventilated patients is increasing. This systematic review and meta-analysis collates existing literature and quantifies the impact of ketamine in mechanically ventilated patients. MATERIALS AND METHODS: EMBASE, MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, conference proceedings, and reference lists were searched. Randomized and nonrandomized studies were included, and two reviewers independently screened abstracts of identified studies for eligibility. RESULTS: Fifteen studies (n = 892 patients) were included. Random effects meta-analytic models revealed that ketamine was associated with a reduction in propofol infusion rate (mean difference in dose, -699 µg/min; 95% CI -1169 to -230, p = .003), but had no impact on fentanyl or midazolam. Ketamine was not associated with mortality, on-target sedation, vasopressor dependence, or hospital length of stay. Cardiovascular complications (e.g. tachycardia and hypertension) were most commonly reported, followed by neurocognitive events, such as agitation and delirium. CONCLUSIONS: The data regarding ketamine use in mechanically ventilated patients is limited in terms of quantity, methodological quality, and demonstrated clinical benefit. Ketamine may play a role as a sedative-sparing agent, but may be associated with harm. High-quality studies are needed before widespread adoption of ketamine earlier in the sedation pathway.

The ED-SED Study: A Multicenter, Prospective Cohort Study of Practice Patterns and Clinical Outcomes Associated With Emergency Department SEDation for Mechanically Ventilated Patients.

OBJECTIVES: To characterize emergency department sedation practices in mechanically ventilated patients, and test the hypothesis that deep sedation in the emergency department is associated with worse outcomes. DESIGN: Multicenter, prospective cohort study. SETTING: The emergency department and ICUs of 15 medical centers. PATIENTS: Mechanically ventilated adult emergency department patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All data involving sedation (medications, monitoring) were recorded. Deep sedation was defined as Richmond Agitation-Sedation Scale of -3 to -5 or Sedation-Agitation Scale of 2 or 1. A total of 324 patients were studied. Emergency department deep sedation was observed in 171 patients (52.8%), and was associated with a higher frequency of deep sedation in the ICU on day 1 (53.8% vs 20.3%; p < 0.001) and day 2 (33.3% vs 16.9%; p = 0.001), when compared to light sedation. Mean (SD) ventilator-free days were 18.1 (10.8) in the emergency department deep sedation group compared to 20.0 (9.8) in the light sedation group (mean difference, 1.9; 95% CI, -0.40 to 4.13). Similar results according to emergency department sedation depth existed for ICU-free days (mean difference, 1.6; 95% CI, -0.54 to 3.83) and hospital-free days (mean difference, 2.3; 95% CI, 0.26-4.32). Mortality was 21.1% in the deep sedation group and 17.0% in the light sedation group (between-group difference, 4.1%; odds ratio, 1.30; 0.74-2.28). The occurrence rate of acute brain dysfunction (delirium and coma) was 68.4% in the deep sedation group and 55.6% in the light sedation group (between-group difference, 12.8%; odds ratio, 1.73; 1.10-2.73). CONCLUSIONS: Early deep sedation in the emergency department is common, carries over into the ICU, and may be associated with worse outcomes. Sedation practice in the emergency department and its association with clinical outcomes is in need of further investigation.

Mechanical Ventilation in the Prehospital and Emergency Department Environment.

Patients who require mechanical ventilation in the prehospital and emergency department environments experience high mortality and are at high risk of ventilator-associated ventilator-induced lung injury and ARDS. In addition, little attention has been given in the literature, trainee education, or clinical emphasis to ventilator management in these patients. ARDS and ventilator-induced lung injury are time-sensitive disease processes that develop early in mechanical ventilation and could potentially be prevented with early lung-protective ventilation. Prehospital and emergency department ventilation, in general, is characterized by potentially injurious tidal volume, high FIO2 , and low PEEP. Recent literature highlights improved subjects outcomes in the setting of early lung-protective ventilation in both subjects with and those without ARDS. This review of the literature led us to recommend that lung-protective ventilation with avoidance of hyperoxia be the default goal ventilator strategy for all patients with prehospital and emergency department mechanical ventilation. This can be achieved by delivering low tidal volumes with stepwise, concurrent titration of FIO2 and PEEP to facilitate adequate oxygenation.

Practice Patterns and Outcomes Associated With Early Sedation Depth in Mechanically Ventilated Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Emerging data suggest that early deep sedation may negatively impact clinical outcomes. This systematic review and meta-analysis defines and quantifies the impact of deep sedation within 48 hours of initiation of mechanical ventilation, as described in the world's literature. The primary outcome was mortality. Secondary outcomes included hospital and ICU lengths of stay, mechanical ventilation duration, and delirium and tracheostomy frequency. DATA SOURCES: The following data sources were searched: MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews and Effects, Cochrane Database of Systematic Reviews databases, ClinicalTrials.gov, conference proceedings, and reference lists. STUDY SELECTION: Randomized controlled trials and nonrandomized studies were included. DATA EXTRACTION: Two reviewers independently screened abstracts of identified studies for eligibility. DATA SYNTHESIS: Nine studies (n = 4,521 patients) published between 2012 and 2017 were included. A random effects meta-analytic model revealed that early light sedation was associated with lower mortality (9.2%) versus deep sedation (27.6%) (odds ratio, 0.34 [0.21-0.54]). Light sedation was associated with fewer mechanical ventilation (mean difference, -2.1; 95% CI, -3.6 to -0.5) and ICU days (mean difference, -3.0 (95% CI, -5.4 to -0.6). Delirium frequency was 28.7% in the light sedation group and 48.5% in the deep sedation group, odds ratio, 0.50 (0.22-1.16). CONCLUSIONS: Deep sedation in mechanically ventilated patients, as evaluated in a small number of qualifying heterogeneous randomized controlled trials and observational studies, was associated with increased mortality and lengths of stay. Interventions targeting early sedation depth assessment, starting in the emergency department and subsequent ICU admission, deserve further investigation and could improve outcome.

Pulmonary Mechanics and Mortality in Mechanically Ventilated Patients Without Acute Respiratory Distress Syndrome: A Cohort Study.

BACKGROUND: Driving pressure has been proposed as a major determinant of outcome in patients with acute respiratory distress syndrome (ARDS), but there is little data examining the association between pulmonary mechanics, including driving pressure, and outcomes in mechanically ventilated patients without ARDS. METHODS: Secondary analysis from 1,705 mechanically ventilated patients enrolled in a clinical study that examined outcomes associated with the use of early lung-protective mechanical ventilation. The primary outcome was mortality and the secondary outcome was the incidence of ARDS. Multivariable models were constructed to: define the association between pulmonary mechanics (driving pressure, plateau pressure, and compliance) and mortality; and evaluate if driving pressure contributed information beyond that provided by other pulmonary mechanics. RESULTS: The mortality rate for the entire cohort was 26.0%. Compared with survivors, non-survivors had significantly higher driving pressure [15.9 (5.4) vs. 14.9 (4.4), P = 0.005] and plateau pressure [21.4 (5.7) vs. 20.4 (4.6), P = 0.001]. Driving pressure was independently associated with mortality [adjusted OR, 1.04 (1.01-1.07)]. Models related to plateau pressure also revealed an independent association with mortality, with similar effect size and interval estimates as driving pressure. There were 152 patients who progressed to ARDS (8.9%). Along with driving pressure and plateau pressure, mechanical power [adjusted OR, 1.03 (1.00-1.06)] was also independently associated with ARDS development. CONCLUSIONS: In mechanically ventilated patients, driving pressure and plateau pressure are risk factors for mortality and ARDS, and provide similar information. Mechanical power is also a risk factor for ARDS.

Practice patterns and outcomes associated with early sedation depth in mechanically ventilated patients: a systematic review protocol.

INTRODUCTION: Mechanical ventilation is a commonly performed intervention in critically ill patients. Frequently, these patients experience deep sedation early in their clinical course. Emerging data suggest that the practice of early deep sedation may negatively impact patient outcomes. The purpose of this review is to assess the world's literature to describe and determine the impact of early deep sedation on the outcomes of mechanically ventilated patients. METHODS AND ANALYSIS: Randomised controlled trials and non-randomised studies will be eligible for inclusion in this systematic review. With the assistance of a medical librarian, we will comprehensively search MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews and Effects, and Cochrane Database of Systematic Reviews for peer-reviewed literature. Grey literature from appropriate professional society conferences, held from 2010 to 2017, will be reviewed manually. Two authors will independently review all search results, and disagreements will be resolved through arbitration by a third author. If appropriate, meta-analysis will be used for quantitative analysis of the data. Heterogeneity between studies will be assessed using the I2 statistic. ETHICS AND DISSEMINATION: The proposed systematic review will not collect data that are associated with individual patients and does not require ethical approval. Results of this study will contribute to the understanding of early sedation, identify future research targets and guide early care in mechanically ventilated patients. TRIAL REGISTRATION NUMBER: This systematic review has been registered in the international prospective register of systematic reviews (PROSPERO #CRD42017057264).

Analgosedation Practices and the Impact of Sedation Depth on Clinical Outcomes Among Patients Requiring Mechanical Ventilation in the ED: A Cohort Study.

BACKGROUND: Analgesia and sedation are cornerstone therapies for mechanically ventilated patients. Despite data showing that early deep sedation in the ICU influences outcome, this has not been investigated in the ED. Therefore, ED-based sedation practices, and their influence on outcome, remain incompletely defined. This study's objectives were to describe ED sedation practices in mechanically ventilated patients and to test the hypothesis that ED sedation depth is associated with worse outcomes. METHODS: This was a cohort study of a prospectively compiled ED registry of adult mechanically ventilated patients at a single academic medical center. Hospital mortality was the primary outcome and hospital-, ICU-, and ventilator-free days were secondary outcomes. A backward stepwise multivariable logistic regression model evaluated the primary outcome as a function of ED sedation depth. Sedation depth was assessed with the Richmond Agitation-Sedation Scale (RASS). RESULTS: Four hundred fourteen patients were studied. In the ED, 354 patients (85.5%) received fentanyl, 254 (61.3%) received midazolam, and 194 (46.9%) received propofol. Deep sedation was observed in 244 patients (64.0%). After adjusting for confounders, a deeper ED RASS was associated with mortality (adjusted OR, 0.77; 95% CI, 0.63-0.94). CONCLUSIONS: Early deep sedation is common in mechanically ventilated ED patients and is associated with worse mortality. These data suggest that ED-based sedation is a modifiable variable that could be targeted to improve outcome.

Lung-Protective Ventilation Initiated in the Emergency Department (LOV-ED): A Quasi-Experimental, Before-After Trial.

STUDY OBJECTIVE: We evaluated the efficacy of an emergency department (ED)-based lung-protective mechanical ventilation protocol for the prevention of pulmonary complications. METHODS: This was a quasi-experimental, before-after study that consisted of a preintervention period, a run-in period of approximately 6 months, and a prospective intervention period. The intervention was a multifaceted ED-based mechanical ventilator protocol targeting lung-protective tidal volume, appropriate setting of positive end-expiratory pressure, rapid oxygen weaning, and head-of-bed elevation. A propensity score-matched analysis was used to evaluate the primary outcome, which was the composite incidence of acute respiratory distress syndrome and ventilator-associated conditions. RESULTS: A total of 1,192 patients in the preintervention group and 513 patients in the intervention group were included. Lung-protective ventilation increased by 48.4% in the intervention group. In the propensity score-matched analysis (n=490 in each group), the primary outcome occurred in 71 patients (14.5%) in the preintervention group compared with 36 patients (7.4%) in the intervention group (adjusted odds ratio 0.47; 95% confidence interval [CI] 0.31 to 0.71). There was an increase in ventilator-free days (mean difference 3.7; 95% CI 2.3 to 5.1), ICU-free days (mean difference 2.4; 95% CI 1.0 to 3.7), and hospital-free days (mean difference 2.4; 95% CI 1.2 to 3.6) associated with the intervention. The mortality rate was 34.1% in the preintervention group and 19.6% in the intervention group (adjusted odds ratio 0.47; 95% CI 0.35 to 0.63). CONCLUSION: Implementing a mechanical ventilator protocol in the ED is feasible and is associated with significant improvements in the delivery of safe mechanical ventilation and clinical outcome.

A Quasi-Experimental, Before-After Trial Examining the Impact of an Emergency Department Mechanical Ventilator Protocol on Clinical Outcomes and Lung-Protective Ventilation in Acute Respiratory Distress Syndrome.

OBJECTIVES: To evaluate the impact of an emergency department mechanical ventilation protocol on clinical outcomes and adherence to lung-protective ventilation in patients with acute respiratory distress syndrome. DESIGN: Quasi-experimental, before-after trial. SETTING: Emergency department and ICUs of an academic center. PATIENTS: Mechanically ventilated emergency department patients experiencing acute respiratory distress syndrome while in the emergency department or after admission to the ICU. INTERVENTIONS: An emergency department ventilator protocol which targeted variables in need of quality improvement, as identified by prior work: 1) lung-protective tidal volume, 2) appropriate setting of positive end-expiratory pressure, 3) oxygen weaning, and 4) head-of-bed elevation. MEASUREMENTS AND MAIN RESULTS: A total of 229 patients (186 preintervention group, 43 intervention group) were studied. In the emergency department, the intervention was associated with significant changes (p < 0.01 for all) in tidal volume, positive end-expiratory pressure, respiratory rate, oxygen administration, and head-of-bed elevation. There was a reduction in emergency department tidal volume from 8.1 mL/kg predicted body weight (7.0-9.1) to 6.4 mL/kg predicted body weight (6.1-6.7) and an increase in lung-protective ventilation from 11.1% to 61.5%, p value of less than 0.01. The intervention was associated with a reduction in mortality from 54.8% to 39.5% (odds ratio, 0.38; 95% CI, 0.17-0.83; p = 0.02) and a 3.9 day increase in ventilator-free days, p value equals to 0.01. CONCLUSIONS: This before-after study of mechanically ventilated patients with acute respiratory distress syndrome demonstrates that implementing a mechanical ventilator protocol in the emergency department is feasible and associated with improved clinical outcomes.

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.