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.

Awareness With Paralysis Among Critically Ill Emergency Department Patients: A Prospective Cohort Study.

OBJECTIVES: In mechanically ventilated patients, awareness with paralysis (AWP) can have devastating consequences, including post-traumatic stress disorder (PTSD), depression, and thoughts of suicide. Single-center data from the emergency department (ED) demonstrate an event rate for AWP factors higher than that reported from the operating room. However, there remains a lack of data on AWP among critically ill, mechanically ventilated patients. The objective was to assess the proportion of ED patients experiencing AWP and investigate modifiable variables associated with its occurrence. DESIGN: An a priori planned secondary analysis of a multicenter, prospective, before-and-after clinical trial. SETTING: The ED of three academic medical centers. PATIENTS: Mechanically ventilated adult patients that received neuromuscular blockers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All data related to sedation and analgesia were collected. AWP was the primary outcome, assessed with the modified Brice questionnaire, and was independently adjudicated by three expert reviewers. Perceived threat, in the causal pathway for PTSD, was the secondary outcome. A total of 388 patients were studied. The proportion of patients experiencing AWP was 3.4% ( n = 13), the majority of whom received rocuronium ( n = 12/13; 92.3%). Among patients who received rocuronium, 5.5% ( n = 12/230) experienced AWP, compared with 0.6% ( n = 1/158) among patients who did not receive rocuronium in the ED (odds ratio, 8.64; 95% CI, 1.11-67.15). Patients experiencing AWP had a higher mean ( sd ) threat perception scale score, compared with patients without AWP (15.6 [5.8] vs 7.7 [6.0]; p < 0.01). CONCLUSIONS: AWP was present in a concerning proportion of mechanically ventilated ED patients, was associated with rocuronium exposure in the ED, and led to increased levels of perceived threat, placing patients at greater risk for PTSD. Studies that aim to further quantify AWP in this vulnerable population and eliminate its occurrence are urgently needed.

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.

Mechanical Ventilation Practices and Low Tidal Volume Ventilation in Air Medical Transport Patients: The AIR-VENT Study.

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 H2O vs 18.0 [15.0-22.0] cm H2O) 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.

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.

Low Tidal Volume Ventilation for Emergency Department Patients: A Systematic Review and Meta-Analysis on Practice Patterns and Clinical Impact.

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.

The AIR-SED Study: A Multicenter Cohort Study of SEDation Practices, Deep Sedation, and Coma Among Mechanically Ventilated AIR Transport Patients.

OBJECTIVES: To characterize prehospital air medical transport sedation practices and test the hypothesis that modifiable variables related to the monitoring and delivery of analgesia and sedation are associated with prehospital deep sedation. DESIGN: Multicenter, retrospective cohort study. SETTING: A nationwide, multicenter (approximately 130 bases) air medical transport provider. PATIENTS: Consecutive, adult mechanically ventilated air medical transport patients treated in the prehospital environment (January 2015 to December 2020). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All data involving sedation (medications, monitoring) were recorded. Deep sedation was defined as: 1) Richmond Agitation-Sedation Scale of -3 to -5; 2) Ramsay Sedation Scale of 5 or 6; or 3) Glasgow Coma Scale of less than or equal to 9. Coma was defined as being unresponsive and based on median sedation depth: 1) Richmond Agitation-Sedation Scale of -5; 2) Ramsay of 6; or 3) Glasgow Coma Scale of 3. A total of 72,148 patients were studied. Prehospital deep sedation was observed in 63,478 patients (88.0%), and coma occurred in 42,483 patients (58.9%). Deeply sedated patients received neuromuscular blockers more frequently and were less likely to have sedation depth documented with a validated sedation depth scale (i.e., Ramsay or Richmond Agitation-Sedation Scale). After adjusting for covariates, a multivariable logistic regression model demonstrated that the use of longer-acting neuromuscular blockers (i.e., rocuronium and vecuronium) was an independent predictor of deep sedation (adjusted odds ratio, 1.28; 95% CI, 1.22-1.35; p < 0.001), while use of a validated sedation scale was associated with a lower odds of deep sedation (adjusted odds ratio, 0.29; 95% CI, 0.27-0.30; p < 0.001). CONCLUSIONS: Deep sedation (and coma) is very common in mechanically ventilated air transport patients and associated with modifiable variables related to the monitoring and delivery of analgesia and sedation. Sedation practices in the prehospital arena and associated clinical outcomes are in need of further investigation.

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.

The ED-AWARENESS Study: A Prospective, Observational Cohort Study of Awareness With Paralysis in Mechanically Ventilated Patients Admitted From the Emergency Department.

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.

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.

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.

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.

Touch engages visual spatial contextual processing.

The spatial context in which we view a visual stimulus strongly determines how we perceive the stimulus. In the visual tilt illusion, the perceived orientation of a visual grating is affected by the orientation signals in its surrounding context. Conceivably, the spatial context in which a visual grating is perceived can be defined by interactive multisensory information rather than visual signals alone. Here, we tested the hypothesis that tactile signals engage the neural mechanisms supporting visual contextual modulation. Because tactile signals also convey orientation information and touch can selectively interact with visual orientation perception, we predicted that tactile signals would modulate the visual tilt illusion. We applied a bias-free method to measure the tilt illusion while testing visual-only, tactile-only or visuo-tactile contextual surrounds. We found that a tactile context can influence visual tilt perception. Moreover, combining visual and tactile orientation information in the surround results in a larger tilt illusion relative to the illusion achieved with the visual-only surround. These results demonstrate that the visual tilt illusion is subject to multisensory influences and imply that non-visual signals access the neural circuits whose computations underlie the contextual modulation of vision.