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.

The Practice Change and Clinical Impact of Lung-Protective Ventilation Initiated in the Emergency Department: A Secondary Analysis of Individual Patient-Level Data From Prior Clinical Trials and Cohort Studies.

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.

Arterial to end-tidal carbon dioxide gap and its characterization in mechanically ventilated adults in the emergency department.

PURPOSE: To evaluate early measurement of the arterial to end-tidal carbon dioxide (PaCO2-PetCO2) gap, a surrogate for physiologic dead space, and its association with clinical outcomes in intubated adults in the emergency department (ED). MATERIALS AND METHODS: Observational cohort study of invasively mechanically ventilated adults in an academic medical center (years 2009 to 2016). The association of the PaCO2-PetCO2 gap was evaluated with respect to clinical outcomes; the primary outcome was in-hospital mortality. RESULTS: 519 patients were included. 325 (63%) patients had an elevated (>5 mmHg) PaCO2-PetCO2. Patients with an elevated PaCO2-PetCO2 were significantly older, had higher APACHE II scores, more frequently had chronic obstructive pulmonary disease (COPD), had lower arterial oxygen to fraction of inspired oxygen (P:F) ratios, and were more likely to be intubated for exacerbation of COPD or sepsis. There was no difference in mortality for patients with an elevated PaCO2-PetCO2 (25% vs 26%) in unadjusted analysis (p = 0.829) or adjusted analysis (aOR = 0.81 [95% CI: 0.53-1.26]), as compared to a non-elevated PaCO2-PetCO2. CONCLUSIONS: An elevated PaCO2-PetCO2 gap is common in the post-intubation period in the ED, but not significantly associated with clinical outcomes.

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.

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.

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.

Validation of a 5-Item Tool to Measure Patient Assessment of Clinician Compassion in Hospitals.

BACKGROUND: We previously validated a 5-item compassion measure to assess patient experience of clinician compassion in the outpatient setting. However, currently, there is no validated and feasible method for health care systems to measure patient experience of clinician compassion in the inpatient setting across multiple hospitals. OBJECTIVE: To test if the 5-item compassion measure can validly and distinctly measure patient assessment of physician and nurse compassion in the inpatient setting. DESIGN: Cross-sectional study between July 1 and July 31, 2020, in a US health care network of 91 community hospitals across 16 states consisting of approximately 15,000 beds. PATIENTS: Adult patients who had an inpatient hospital stay and completed the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. MEASUREMENTS: We adapted the original 5-item compassion measure to be specific for physicians, as well as for nurses. We disseminated both measures with the HCAHPS survey and used confirmatory factor analysis for validity testing. We tested reliability using Cronbach's alpha, as well as convergent validity with patient assessment of physician and nursing communication and overall hospital rating questions from HCAHPS. RESULTS: We analyzed 4756 patient responses. Confirmatory factor analysis found good fit for two distinct constructs (i.e., physician and nurse compassion). Both measures demonstrated good internal consistency (alpha > 0.90) and good convergent validity but reflected a construct (compassionate care) distinct from what is currently captured in HCAHPS. CONCLUSION: We validated two 5-item tools that can distinctly measure patient experience of physician and nurse compassion for use in the inpatient hospital setting in conjunction with HCAHPS.

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.

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.

Delays in reporting and publishing trial results during pandemics: cross sectional analysis of 2009 H1N1, 2014 Ebola, and 2016 Zika clinical trials.

BACKGROUND: Pandemic events often trigger a surge of clinical trial activity aimed at rapidly evaluating therapeutic or preventative interventions. Ensuring rapid public access to the complete and unbiased trial record is particularly critical for pandemic research given the urgent associated public health needs. The World Health Organization (WHO) established standards requiring posting of results to a registry within 12 months of trial completion and publication in a peer reviewed journal within 24 months of completion, though compliance with these requirements among pandemic trials is unknown. METHODS: This cross-sectional analysis characterizes availability of results in trial registries and publications among registered trials performed during the 2009 H1N1 influenza, 2014 Ebola, and 2016 Zika pandemics. We searched trial registries to identify clinical trials testing interventions related to these pandemics, and determined the time elapsed between trial completion and availability of results in the registry. We also performed a comprehensive search of MEDLINE via PubMed, Google Scholar, and EMBASE to identify corresponding peer reviewed publications. The primary outcome was the compliance with either of the WHO's established standards for sharing clinical trial results. Secondary outcomes included compliance with both standards, and assessing the time elapsed between trial completion and public availability of results. RESULTS: Three hundred thirty-three trials met eligibility criteria, including 261 H1N1 influenza trials, 60 Ebola trials, and 12 Zika trials. Of these, 139 (42%) either had results available in the trial registry within 12 months of study completion or had results available in a peer-reviewed publication within 24 months. Five trials (2%) met both standards. No results were available in either a registry or publication for 59 trials (18%). Among trials with registered results, a median of 42 months (IQR 16-76 months) elapsed between trial completion and results posting. For published trials, the median elapsed time between completion and publication was 21 months (IQR 9-34 months). Results were available within 24 months of study completion in either the trial registry or a peer reviewed publication for 166 trials (50%). CONCLUSIONS: Very few trials performed during prior pandemic events met established standards for the timely public dissemination of trial results.

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.

Effects of hypercapnia in sepsis: A scoping review of clinical and pre-clinical data.

BACKGROUND: Perform a scoping review of (1) pre-clinical studies testing the physiological effects of higher PaCO2 levels in the setting of sepsis models and (2) clinical investigations testing the effects of hypercapnia on clinical outcomes in mechanically ventilated patients with sepsis. METHODS: We performed a search of CENTRAL, PUBMED, CINAHL, and EMBASE. Study inclusion criteria for pre-clinical studies were: (1) bacterial sepsis model (2) measurement of PaCO2 , and (3) comparison of outcome measure between different PaCO2 levels. Inclusion criteria for clinical studies were: (1) diagnosis of sepsis, (2) receiving invasive mechanical ventilation, (3) measurement of PaCO2 , and (4) comparison of outcomes between different PaCO2 levels. We performed a qualitative analysis to collate and summarize the physiological and clinical effects of hypercapnia according to the recommended methodology from the Cochrane Handbook. RESULTS: Fifteen pre-clinical and nine clinical studies were included. Among pre-clinical studies, the individual studies found higher PaCO2 augments tissue blood flow and oxygenation, and attenuates inflammation and lung injury; however, all pre-clinical studies were found to have some degree of risk of bias. Six of the nine clinical studies were deemed to be good quality. Among clinical studies hypercapnia was associated with increased cerebral perfusion and oxygenation; however, there were conflicting results testing the association between hypercapnia and mortality. CONCLUSION: While individual pre-clinical studies identified potential mechanisms by which changes in PaCO2 levels could affect pathophysiology in sepsis, there is a paucity of clinical data as to the optimal PaCO2 range, demonstrating a need for future research. REGISTRATION: PROSPERO number CRD42018086703.

Incidence and significance of injuries on secondary CT imaging after initial selective imaging in blunt trauma patients.

OBJECTIVE: It is unclear if additional computerized tomography (CT) imaging is warranted after injuries are identified on CT in blunt trauma patients. The objective of this study was to determine the incidence and significance of injuries identified on secondary CT imaging after identification of injuries on initial CTs in blunt trauma patients. METHODS: This was a retrospective cohort study at an academic Level 1 trauma center with a two-tiered trauma system. INCLUSION CRITERIA: age ≥ 18, level 2 trauma activation, injury identified on initial CT, and secondary CTs ordered. Secondary injuries were categorized as resulting in: no changes, minor changes, or major changes in management. RESULTS: 537 patients underwent 1179 initial CT scans which identified 744 injuries. There were 1094 secondary CTs which identified 143 additional injuries in 94 (18%) patients. 9 (1.7%) patients had at least one major management change and 64 (12%) had at least one minor management change. Rib fracture(s) was the most common injury on secondary scans [45/143 (32%)]. The major management changes were: tube thoracostomy for pneumothorax (4 patients), blood transfusion for hemoperitoneum (1 patient), surgery for acetabular fracture (1 patient), thoracolumbar brace for spine fracture (2 patients) and angiography for splenic injury (1 patient). CONCLUSION: While a significant proportion of patients (18%) had injuries on secondary CT, only 1.7% of patients had a resultant major management change. Future research is warranted to determine the need for additional CT imaging after an initial selective imaging strategy in blunt trauma patients.

Association Between Early Hyperoxia Exposure After Resuscitation From Cardiac Arrest and Neurological Disability: Prospective Multicenter Protocol-Directed Cohort Study.

BACKGROUND: Studies examining the association between hyperoxia exposure after resuscitation from cardiac arrest and clinical outcomes have reported conflicting results. Our objective was to test the hypothesis that early postresuscitation hyperoxia is associated with poor neurological outcome. METHODS: This was a multicenter prospective cohort study. We included adult patients with cardiac arrest who were mechanically ventilated and received targeted temperature management after return of spontaneous circulation. We excluded patients with cardiac arrest caused by trauma or sepsis. Per protocol, partial pressure of arterial oxygen (Pao2) was measured at 1 and 6 hours after return of spontaneous circulation. Hyperoxia was defined as a Pao2 >300 mm Hg during the initial 6 hours after return of spontaneous circulation. The primary outcome was poor neurological function at hospital discharge, defined as a modified Rankin Scale score >3. Multivariable generalized linear regression with a log link was used to test the association between Pao2 and poor neurological outcome. To assess whether there was an association between other supranormal Pao2 levels and poor neurological outcome, we used other Pao2 cut points to define hyperoxia (ie, 100, 150, 200, 250, 350, 400 mm Hg). RESULTS: Of the 280 patients included, 105 (38%) had exposure to hyperoxia. Poor neurological function at hospital discharge occurred in 70% of patients in the entire cohort and in 77% versus 65% among patients with versus without exposure to hyperoxia respectively (absolute risk difference, 12%; 95% confidence interval, 1-23). Hyperoxia was independently associated with poor neurological function (relative risk, 1.23; 95% confidence interval, 1.11-1.35). On multivariable analysis, a 1-hour-longer duration of hyperoxia exposure was associated with a 3% increase in risk of poor neurological outcome (relative risk, 1.03; 95% confidence interval, 1.02-1.05). We found that the association with poor neurological outcome began at ≥300 mm Hg. CONCLUSIONS: Early hyperoxia exposure after resuscitation from cardiac arrest was independently associated with poor neurological function at hospital discharge.

Association Between Elevated Mean Arterial Blood Pressure and Neurologic Outcome After Resuscitation From Cardiac Arrest: Results From a Multicenter Prospective Cohort Study.

OBJECTIVES: Laboratory studies suggest elevated blood pressure after resuscitation from cardiac arrest may be protective; however, clinical data are limited. We sought to test the hypothesis that elevated postresuscitation mean arterial blood pressure is associated with neurologic outcome. DESIGN: Preplanned analysis of a prospective cohort study. SETTING: Six academic hospitals in the United States. PATIENTS: Adult, nontraumatic cardiac arrest patients treated with targeted temperature management after return of spontaneous circulation. INTERVENTIONS: Mean arterial blood pressure was measured noninvasively after return of spontaneous circulation and every hour during the initial 6 hours after return of spontaneous circulation. MEASURES AND MAIN RESULTS: We calculated the mean arterial blood pressure and a priori dichotomized subjects into two groups: mean arterial blood pressure 70-90 and greater than 90 mm Hg. The primary outcome was good neurologic function, defined as a modified Rankin Scale less than or equal to 3. The modified Rankin Scale was prospectively determined at hospital discharge. Of the 269 patients included, 159 (59%) had a mean arterial blood pressure greater than 90 mm Hg. Good neurologic function at hospital discharge occurred in 30% of patients in the entire cohort and was significantly higher in patients with a mean arterial blood pressure greater than 90 mm Hg (42%) as compared with mean arterial blood pressure 70-90 mm Hg (15%) (absolute risk difference, 27%; 95% CI, 17-37%). In a multivariable Poisson regression model adjusting for potential confounders, mean arterial blood pressure greater than 90 mm Hg was associated with good neurologic function (adjusted relative risk, 2.46; 95% CI; 2.09-2.88). Over ascending ranges of mean arterial blood pressure, there was a dose-response increase in probability of good neurologic outcome, with mean arterial blood pressure greater than 110 mm Hg having the strongest association (adjusted relative risk, 2.97; 95% CI, 1.86-4.76). CONCLUSIONS: Elevated blood pressure during the initial 6 hours after resuscitation from cardiac arrest was independently associated with good neurologic function at hospital discharge. Further investigation is warranted to determine if targeting an elevated mean arterial blood pressure would improve neurologic outcome after cardiac arrest.

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.

Validation of a 5-item tool to measure patient assessment of clinician compassion in the emergency department.

BACKGROUND: To test if the 5-item compassion measure (a tool previously validated in the outpatient setting to measure patient assessment of clinician compassion) is a valid and reliable tool to quantify a distinct construct (i.e. clinical compassion) among patients evaluated in the emergency department (ED). METHODS: Cross-sectional study conducted in three academic emergency departments in the U.S. between November 2018 and April 2019. We enrolled adult patients who were evaluated in the EDs of the participating institutions and administered the 5-item compassion measure after completion of care in the ED. Validity testing was performed using confirmatory factor analysis. Cronbach's alpha was used to test reliability. Convergent validity with patient assessment of overall satisfaction questions was tested using Spearman correlation coefficients and we tested if the 5-item compassion measure assessed a construct distinct from overall patient satisfaction using confirmatory factor analysis. RESULTS: We analyzed 866 patient responses. Confirmatory factor analysis found all five items loaded well on a single construct and our model was found to have good fit. Reliability was excellent (Cronbach's alpha = 0.93) among the entire cohort. These results remained consistent on sub-analyses stratified by individual institutions. The 5-item compassion measure had moderate correlation with overall patient satisfaction (r = 0.66) and patient recommendation of the ED to friends and family (r = 0.57), but reflected a patient experience domain (i.e. compassionate care) distinctly different from patient satisfaction. CONCLUSIONS: The 5-item compassion measure is a valid and reliable tool to measure patient assessment of clinical compassion in the ED.

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.

Early Interventions for the Prevention of Posttraumatic Stress Symptoms in Survivors of Critical Illness: A Qualitative Systematic Review.

OBJECTIVES: Posttraumatic stress disorder among survivors of critical illness is of public health importance, as it is common and reduces patient quality of life. The objective of this systematic review was to collate the world's literature on interventions aimed at preventing posttraumatic stress disorder among survivors of critical illness. DATA SOURCES: We performed a search of CENTRAL, MEDLINE, EMBASE, CINAHL, and clinical trials registry platforms, with no restriction to language using a comprehensive strategy. STUDY SELECTION: Study inclusion criteria were as follows: 1) adult human subjects, 2) patients treated in an ICU setting, 3) intervention arm aimed at reducing posttraumatic stress disorder symptoms, 4) use of a control arm, and 5) an outcome measure assessing development of acute stress or posttraumatic stress disorder symptoms. DATA EXTRACTION: We performed a qualitative analysis to collate and summarize effects of identified interventions according to the recommended methodology from the Cochrane Handbook. DATA SYNTHESIS: Seventeen studies met all inclusion and no exclusion criteria. There was heterogeneity in interventions and outcome measures used. All studies had some concern for risk of bias as per the Cochrane tool for assessing risk of bias. In eight of 12 studies (67%) testing early interventions (i.e., initiated in the ICU course) and one of five studies (20%) testing delayed interventions following ICU discharge, posttraumatic stress disorder symptoms were decreased among the intervention group compared with controls. CONCLUSIONS: Despite a paucity of high-quality clinical investigations, the preponderance of evidence to date suggests that 1) posttraumatic stress disorder among survivors of critical illness may be preventable and 2) early interventions may be the most effective.

Association Between Partial Pressure of Arterial Carbon Dioxide and Survival to Hospital Discharge Among Patients Diagnosed With Sepsis in the Emergency Department.

OBJECTIVE: The objective of this study was to test the association between the partial pressure of arterial carbon dioxide and survival to hospital discharge among mechanically ventilated patients diagnosed with sepsis in the emergency department. DESIGN: Retrospective cohort study of a single center trial registry. SETTING: Academic medical center. PATIENTS: Mechanically ventilated emergency department patients. INCLUSION CRITERIA: age 18 years and older, diagnosed with sepsis in the emergency department, and mechanical ventilation initiated in the emergency department. INTERVENTIONS: Arterial blood gases obtained after initiation of mechanical ventilation were analyzed. The primary outcome was survival to hospital discharge. We tested the association between partial pressure of arterial carbon dioxide and survival using multivariable logistic regression adjusting for potential confounders. Sensitivity analyses, including propensity score matching were also performed. MEASUREMENTS AND MAIN RESULTS: Six hundred subjects were included, and 429 (72%) survived to hospital discharge. The median (interquartile range) partial pressure of arterial carbon dioxide was 42 (34-53) mm Hg for the entire cohort and 44 (35-57) and 39 (31-45) mm Hg among survivors and nonsurvivors, respectively (p < 0.0001 Wilcox rank-sum test). On multivariable analysis, a 1 mm Hg rise in partial pressure of arterial carbon dioxide was associated with a 3% increase in odds of survival (adjusted odds ratio, 1.03; 95% CI, 1.01-1.04) after adjusting for tidal volume and other potential confounders. These results remained significant on all sensitivity analyses. CONCLUSION: In this sample of mechanically ventilated sepsis patients, we found an association between increasing levels of partial pressure of arterial carbon dioxide and survival to hospital discharge. These findings justify future studies to determine the optimal target partial pressure of arterial carbon dioxide range for mechanically ventilated sepsis patients.