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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 (pCO 2 ) 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 pCO 2 and outcomes, with higher pCO 2 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 pCO 2 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 pCO 2 based on pH in the ED may be a potential intervention target for future clinical trials to improve clinical outcomes., Competing Interests: Declaration of competing interest On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Mechanically ventilated emergency department (ED) patients experience high morbidity and mortality. In a prior trial at our center, ED-based lung-protective ventilation was associated with improved care delivery and outcomes. Whether this strategy has persisted in the years after the trial remains unclear. The objective was to assess practice change and clinical outcomes associated with ED lung-protective ventilation., Design: Secondary analysis of individual patient-level data from prior clinical trials and cohort studies., Setting: ED and ICUs of a single academic center., Patients: Mechanically ventilated adults., Interventions: A lung-protective ventilator protocol used as the default approach in the ED., Measurements and Main Results: The primary ventilator-related outcome was tidal volume, and the primary clinical outcome was hospital mortality. Secondary outcomes included ventilator-, hospital-, and ICU-free days. Multivariable logistic regression, propensity score (PS)-adjustment, and multiple a priori subgroup analyses were used to evaluate outcome as a function of the intervention. A total of 1,796 patients in the preintervention period and 1,403 patients in the intervention period were included. In the intervention period, tidal volume was reduced from 8.2 mL/kg predicted body weight (PBW) (7.3-9.1) to 6.5 mL/kg PBW (6.1-7.1), and low tidal volume ventilation increased from 46.8% to 96.2% ( p < 0.01). The intervention period was associated with lower mortality (35.9% vs 19.1%), remaining significant after multivariable logistic regression analysis (adjusted odds ratio [aOR], 0.43; 95% CI, 0.35-0.53; p < 0.01). Similar results were seen after PS adjustment and in subgroups. The intervention group had more ventilator- (18.8 [10.1] vs 14.1 [11.9]; p < 0.01), hospital- (12.2 [9.6] vs 9.4 [9.5]; p < 0.01), and ICU-free days (16.6 [10.1] vs 13.1 [11.1]; p < 0.01)., Conclusions: ED lung-protective ventilation has persisted in the years since implementation and was associated with improved outcomes. These data suggest the use of ED-based lung-protective ventilation as a means to improve outcome., Competing Interests: Dr. Kollef is supported by the Barnes-Jewish Hospital Foundation. Dr. Fuller is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R34HL150404. Dr. Carpenter is supported by the National Institute of Aging under award numbers R21/R33AG058926 and R61/R33 AG069822. Drs. Fuller, Yan, and Roberts received support for article research from the National Institutes of Health. Dr. Mohr’s institution received funding from ESSOS. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

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., Competing Interests: Drs. Fuller’s, Roberts’, and Mohr’s institutions received funding from the National Heart, Lung, and Blood Institute. Drs. Fuller, Roberts, Mohr, Faine, and Yan received support for article research from the National Institutes of Health. Dr. Fuller is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R34HL150404. Dr. Kollef is supported by the Barnes-Jewish Hospital Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: The management of mechanical ventilation critically impacts outcome for patients with acute respiratory failure. Ventilator settings in the early post-intubation period may be especially influential on outcome. Low tidal volume ventilation in the prehospital setting has been shown to impact the provision of low tidal volume after admission and influence outcome. However, there is an overall paucity of data on mechanical ventilation for air medical transport patients. The objectives of this study were to characterize air medical transport ventilation practices and assess variables associated with nonprotective ventilation., Methods: This was a multi-center, nationwide (approximately 130 bases) retrospective cohort study conducted on consecutive, adult mechanically ventilated air medical transport patients treated in the prehospital environment. Descriptive statistics were used to assess the cohort; the chi-square test compared categorical variables, and continuous variables were compared using independent samples t test or Mann-Whitney U test. To assess for predictors of nonprotective ventilation, a multivariable logistic regression model was constructed to adjust for potentially confounding variables. Low tidal volume ventilation was defined as a tidal volume of ≤ 8 mL/kg predicted body weight (PBW)., Results: A total of 68,365 subjects were studied. Height was documented in only 4,186 (6.1%) subjects. Significantly higher tidal volume/PBW (8.6 [8.3-9.2] mL vs 6.5 [6.1-7.0] mL) and plateau pressure (20.0 [16.5-25.0] cm H 2 O vs 18.0 [15.0-22.0] cm H 2 O) were seen in the nonpro-tective ventilation group (P < .001 for both). According to sex, females received higher tidal volume/PBW compared to males (7.4 [6.6-8.0] mL vs 6.4 [6.0-6.8] mL, P < .001) and composed 75% of those subjects with nonprotective ventilation compared to 25% male, P < .001. After multivariable logistic regression, female sex was an independent predictor of nonprotective ventilation (adjusted odds ratio 6.79 [95% CI 5.47-8.43], P < .001)., Conclusions: The overwhelming majority of air medical transport subjects had tidal volume set empirically, which may be exposing patients to nonprotective ventilator settings. Given a lack of PBW assessments, the frequency of low tidal volume use remains unknown. Performance improvement initiatives aimed at indexing tidal volume to PBW are easy targets to improve the delivery of mechanical ventilation in the prehospital arena, especially for females., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2022 by Daedalus Enterprises.)

Objectives: Data suggest that low tidal volume ventilation (LTVV) initiated in the emergency department (ED) has a positive impact on outcome. This systematic review and meta-analysis quantify the impact of ED-based LTVV on outcomes and ventilator settings in the ED and ICU., Data Sources: We systematically reviewed MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, references, conferences, and ClinicalTrials.gov., Study Selection: Randomized and nonrandomized studies of mechanically ventilated ED adults were eligible., Data Extraction: Two reviewers independently screened abstracts. The primary outcome was mortality. Secondary outcomes included ventilation duration, lengths of stay, and occurrence rate of acute respiratory distress syndrome (ARDS). We assessed impact of ED LTVV interventions on ED and ICU tidal volumes., Data Synthesis: The search identified 1,023 studies. Eleven studies (n = 12,912) provided outcome data and were meta-analyzed; 10 additional studies (n = 1,863) provided descriptive ED tidal volume data. Overall quality of evidence was low. Random effect meta-analytic models revealed that ED LTVV was associated with lower mortality (26.5%) versus non-LTVV (31.1%) (odds ratio, 0.80 [0.72-0.88]). ED LTVV was associated with shorter ICU (mean difference, -1.0; 95% CI, -1.7 to -0.3) and hospital (mean difference, -1.2; 95% CI, -2.3 to -0.1) lengths of stay, more ventilator-free days (mean difference, 1.4; 95% CI, 0.4-2.4), and lower occurrence rate (4.5% vs 8.3%) of ARDS (odds ratio, 0.57 [0.44-0.75]). ED LTVV interventions were associated with reductions in ED (-1.5-mL/kg predicted body weight [PBW] [-1.9 to -1.0]; p < 0.001) and ICU (-1.0-mL/kg PBW [-1.8 to -0.2]; p = 0.01) tidal volume., Conclusions: The use of LTVV in the ED is associated with improved clinical outcomes and increased use of lung protection, recognizing low quality of evidence in this domain. Interventions aimed at implementing and sustaining LTVV in the ED should be explored., Competing Interests: Dr. Fuller is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) under award number R34HL150404. Dr. Palmer’s institution received funding from the Barnes Jewish Foundation grant and Washington University Department of Anesthesia; he disclosed he is an Omnicure seed investor. Dr. Ablordeppey’s institution received funding from the National Heart, Lung, and Blood Institute. Dr. Fuller’s institution received funding from the National Institutes of Health NIH (R34HL150404); he received support for article research from the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Funders played no role in the following features of the study: study design, data collection, data management, data analysis, data interpretation, writing of the manuscript, or decision to submit the article for publication. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Study Objective: Awareness with paralysis is a devastating complication for patients receiving mechanical ventilation and risks long-term psychological morbidity. Data from the emergency department (ED) demonstrate a high rate of longer-acting neuromuscular blocking agent use, delayed analgosedation, and a lack of sedation depth monitoring. These practices are discordant with recommendations for preventing awareness with paralysis. Despite this, awareness with paralysis has not been rigorously studied in the ED population. Our objective is to assess the prevalence of awareness with paralysis in ED patients receiving mechanical ventilation., Methods: This was a single-center, prospective, observational cohort study on 383 mechanically ventilated ED patients. After extubation, we assessed patients for awareness with paralysis by using the modified Brice questionnaire. Three expert reviewers independently adjudicated awareness with paralysis. We report the prevalence of awareness with paralysis (primary outcome); the secondary outcome was perceived threat, a mediator for development of posttraumatic stress disorder., Results: The prevalence of awareness with paralysis was 2.6% (10/383). Exposure to rocuronium at any point in the ED was significantly different between patients who experienced awareness with paralysis (70%) versus the rest of the cohort (31.4%) (unadjusted odds ratio 5.1; 95% confidence interval 1.30 to 20.1). Patients experiencing awareness with paralysis had higher mean values on the threat perception scale, denoting a higher degree of perceived threat, compared with patients who did not experience awareness with paralysis (13.4 [SD 7.7] versus 8.5 [SD 6.2]; mean difference 4.9; 95% confidence interval 0.94 to 8.8)., Conclusion: Awareness with paralysis occurs in a significant minority of ED patients who receive mechanical ventilation. Potential associations of awareness with paralysis with ED care and increased perceived threat warrant further evaluation., (Copyright © 2020 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Mr. Pappal received funding from the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) under Award Number TL1TR002344, Principal investigator: Jay F. Piccirillo, MD, FACS. Project Title: Washington University Institute of Clinical and Translational Sciences. Mr. Winkler was supported by the NIH T35 National Heart, Lung, and Blood Institute Training Grant, Grant Number 5T35HL007815, Principal investigator: Koong-Nah Chung, PhD. Dr. Fuller was supported by a grant-in-aid from the Division of Clinical and Translational Research of the Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

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 2 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: In mechanically ventilated patients, sedation strategies are a major determinant of outcome. The emergency department (ED) is the earliest exposure to mechanical ventilation for hundreds of thousands of patients annually in the USA. The one retrospective study that exists regarding ED sedation for mechanically ventilated patients showed a strong association between deep sedation in the ED and worse clinical outcomes. This finding suggests that the ED may be an optimal location to study the impact of early sedation on outcome, yet a lack of prospective studies represents a knowledge gap in this arena. This protocol describes a prospective observational study aimed at further characterising ED sedation practices and assessing the relationship between ED sedation and clinical outcomes. An association between ED sedation and clinical outcomes across multiple sites would suggest the need for changes in the current sedation strategies used in the ED, and provide evidence for future interventional studies in this field., Methods and Analysis: This is a multicentre, prospective cohort study testing the hypothesis that deep sedation in the ED is associated with worse clinical outcomes. A cohort of over 300 mechanically ventilated ED patients will be included. The primary outcome is ventilator-free days, and secondary outcomes include hospital mortality, incidence of acute brain dysfunction and lengths of stay. Multivariable linear regression will test the hypothesis that deep sedation in the ED is associated with a decrease in ventilator-free days., Ethics and Dissemination: Approval of the study by the Institutional Review Board (IRB) at each participating site has been obtained prior to data collection on the first patient. 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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.

Background: Providing supplemental oxygen is fundamental in the management of mechanically ventilated patients. Increasing amounts of data show worse clinical outcomes associated with hyperoxia. However, these previous data in the critically ill have not focused on outcomes associated with brief hyperoxia exposure immediately after endotracheal intubation. Therefore, the objectives of this study were to evaluate the impact of isolated early hyperoxia exposure in the emergency department (ED) on clinical outcomes among mechanically ventilated patients with subsequent normoxia in the intensive care unit (ICU)., Methods: This was an observational cohort study conducted in the ED and ICUs of an academic center in the USA. Mechanically ventilated normoxic (partial pressure of arterial oxygen (P a O 2 ) 60-120 mm Hg) ICU patients with mechanical ventilation initiated in the ED were studied. The cohort was categorized into three oxygen exposure groups based on P a O 2 values obtained after ED intubation: hypoxia, normoxia, and hyperoxia (defined as P a O 2  < 60 mmHg, P a O 2 60-120 mm Hg, and P a O 2  > 120 mm Hg, respectively, based on previous literature)., Results: A total of 688 patients were included. ED normoxia occurred in 350 (50.9%) patients, and 300 (43.6%) had exposure to ED hyperoxia. The ED hyperoxia group had a median (IQR) ED P a O 2 of 189 mm Hg (146-249), compared to an ED P a O 2 of 88 mm Hg (76-101) in the normoxia group, P < 0.001. Patients with ED hyperoxia had greater hospital mortality (29.7%), when compared to those with normoxia (19.4%) and hypoxia (13.2%). After multivariable logistic regression analysis, ED hyperoxia was an independent predictor of hospital mortality (adjusted OR 1.95 (1.34-2.85))., Conclusions: ED exposure to hyperoxia is common and associated with increased mortality in mechanically ventilated patients achieving normoxia after admission. This suggests that hyperoxia in the immediate post-intubation period could be particularly injurious, and targeting normoxia from initiation of mechanical ventilation may improve outcome.

Objective: Patients with prolonged mechanical ventilation (PMV) represent important "outliers" of hospital length of stay (LOS) and costs (∼$26 billion annually in the United States). We tested the hypothesis that a Lean Six Sigma (LSS) approach for process improvement could reduce hospital LOS and the associated costs of care for patients with PMV., Design: Before-and-after cohort study., Setting: Multidisciplinary intensive care unit (ICU) in an academic medical center., Patients: Adult patients admitted to the ICU and treated with PMV, as defined by diagnosis-related group (DRG)., Methods: We implemented a clinical redesign intervention based on LSS principles. We identified eight distinct processes in preparing patients with PMV for post-acute care. Our clinical redesign included reengineering daily patient care rounds ("Lean ICU rounds") to reduce variation and waste in these processes. We compared hospital LOS and direct cost per case in patients with PMV before (2013) and after (2014) our LSS intervention., Results: Among 259 patients with PMV (131 preintervention; 128 postintervention), median hospital LOS decreased by 24% during the intervention period (29 vs. 22 days, p < .001). Accordingly, median hospital direct cost per case decreased by 27% ($66,335 vs. $48,370, p < .001)., Conclusion: We found that a LSS-based clinical redesign reduced hospital LOS and the costs of care for patients with PMV.

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., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the prevalence of hypocapnia and hypercapnia during the earliest period of mechanical ventilation, and determine the association between P a CO 2 and mortality., Materials and Methods: A cohort study using an emergency department registry of mechanically ventilated patients. P a CO 2 was categorized: hypocapnia (<35mmHg), normocapnia (35-45mmHg), and hypercapnia (>45mmHg). The primary outcome was survival to hospital discharge., Results: A total of 1,491 patients were included. Hypocapnia occurred in 375 (25%) patients and hypercapnia in 569 (38%). Hypercapnia (85%) had higher survival rate compared to normocapnia (74%) and hypocapnia (66%), P<0.001. P a CO 2 was an independent predictor of survival to hospital discharge [hypocapnia (aOR 0.65 (95% confidence interval [CI] 0.48-0.89), normocapnia (reference category), hypercapnia (aOR 1.83 (95% CI 1.32-2.54)]. Over ascending ranges of P a CO 2 , there was a linear trend of increasing survival up to a P a CO 2 range of 66-75mmHg, which had the strongest survival association, aOR 3.18 (95% CI 1.35-7.50)., Conclusions: Hypocapnia and hypercapnia occurred frequently after initiation of mechanical ventilation. Higher P a CO 2 levels were associated with increased survival. These data provide rationale for a trial examining the optimal P a CO 2 in the critically ill., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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 I 2 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)., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Prolonged dependence on mechanical ventilation after critical illness is an emerging public health challenge; however, long-term outcomes are incompletely understood. We aimed to systematically analyse long-term survival of critically ill patients treated with prolonged mechanical ventilation., Methods: We searched PubMed, CINAHL, and the Cochrane Library between 1988 and Nov 6, 2013, with no language restrictions, for studies on prolonged mechanical ventilation. We included studies of adult populations treated with mechanical ventilation for more than 14 days, who were admitted to a ventilator weaning unit, or who had a tracheostomy for acute respiratory failure. We abstracted data with a standardised collection template and assessed study quality (ie, risk of bias) using a customised Newcastle-Ottawa Scale. We did a stratified analysis based on study setting (eg, acute vs post-acute care hospitals), and used a random-effects model to calculate pooled statistics (proportions with 95% CIs) for all outcomes. We did sensitivity analyses based on study quality (ie, high-quality studies only) and country of origin (USA vs non-USA and USA vs UK). The primary outcome was mortality at 1 year. Secondary outcomes were in-hospital mortality, discharge destination among survivors, successful liberation from mechanical ventilation while in hospital, and mortality at timepoints longer than 1 year., Findings: Of 6326 studies identified, 402 underwent full manuscript review, and 124 studies from 16 countries met the inclusion criteria. 39 studies reported mortality at 1 year, which was 59% (95% CI 56-62). Among the 29 high-quality studies, the pooled mortality at 1 year was 62% (95% CI 57-67). Pooled mortality at hospital discharge was 29% (95% CI 26-32). However, only 19% (16-24) were discharged to home and only 50% (47-53) were successfully liberated from mechanical ventilation. For studies in post-acute care hospitals, outcomes were worse in the USA than internationally (mortality at 1 year was 73% [95% CI 67-78] in the USA vs 47% [29-65] in non-USA countries; in-hospital mortality was 31% [26-37] vs 18% [14-24]; and liberation from ventilation was 47% [42-51] vs 63% [59-68]; p<0·0001 for all)., Interpretation: Although a high proportion of patients survived to hospital discharge, fewer than half of patients survived beyond 1 year. Future studies should focus on optimum patient selection for prolonged mechanical ventilation and integration of long-term outcome information into clinical decision making., Funding: Cooper University Health Care and Cooper Medical School of Rowan University., (Copyright © 2015 Elsevier Ltd. All rights reserved.)