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.

Dexmedetomidine in the emergency department: A prospective observational cohort study.

BACKGROUND: Dexmedetomidine (DEX) is a centrally acting sympatholytic sedative. Abundant evidence from the intensive care unit and other settings demonstrates that the use of DEX is associated with improved sedation-related outcomes. There is a paucity of data on the use and efficacy of DEX in the emergency department (ED). METHODS: We performed a prospective single-center observational cohort study of patients treated with intravenous DEX for any indication in the ED. We performed serial bedside evaluations of sedation depth and delirium and administered standardized questionnaires to ED physicians about their use of DEX. We assessed the incidence of hemodynamic adverse events (HAEs; bradycardia or hypotension), clinically significant HAEs (HAEs accompanied by clinical intervention or discontinuation of DEX), sedation-related ED outcomes, and clinician perception of DEX effectiveness. RESULTS: We enrolled 75 patients treated with DEX in the ED during our study period. The most common indication for DEX was noninvasive positive pressure ventilation (32 patients, 43%). DEX was administered in the ED for a median of 2.6 h (interquartile range [IQR] 1.6-4.9 h), with a median infusion rate of 0.3 µg/kg/h (IQR 0.2-0.4 µg/kg/h). Clinically significant HAE occurred in nine patients (12%, 95% CI 6%-22%). Other sedative or analgesic infusions were administered in the ED to 21 patients (28%). Clinicians felt DEX was highly effective (median [IQR] effectiveness score of 5 [3-5] on a 5-point Likert scale). The median (IQR) ED Richmond Agitation Sedation Scale post-DEX was -1 (-4 to 0). CONCLUSIONS: DEX is used in the ED for diverse indications. Additional data from larger cohorts and comparative studies are required to determine the precise incidence of clinically significant HAE associated with DEX use in the ED. ED clinicians have a positive perception of the effectiveness of DEX.

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.

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.

The impact of telehealth in sepsis care: A systematic review.

OBJECTIVES: Sepsis is associated with significant mortality. Telehealth may improve the quality of early sepsis care, but the use and impact of telehealth applications for sepsis remain unclear. We aim to describe the telehealth interventions that have been used to facilitate sepsis care, and to summarize the reported effect of telehealth on sepsis outcomes. DATA SOURCES: We identified articles reporting telehealth use for sepsis using an English-language search of PubMed, CINAHL Plus (EBSCO), Academic Search Ultimate (EBSCO), APA PsycINFO (EBSCO), Public Health (ProQuest), and Web of Science databases with no restrictions on publication date. STUDY SELECTION: Included studies described the use of telehealth as an intervention for treating sepsis. Only comparative effectiveness analyses were included. DATA EXTRACTION AND SYNTHESIS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) guidelines, two investigators independently selected articles for inclusion and abstracted data. A random-effects subgroup analysis was conducted on patient survival treated with and without telehealth. RESULTS: A total of 15 studies were included, involving 188,418 patients with sepsis. Thirteen studies used observational study designs, and the most common telehealth applications were provider-to-provider telehealth consultation and intensive care unit telehealth. Clinical and methodological heterogeneity was significantly high. Telehealth use was associated with higher survival, especially in settings with low control group survival. The effect of telehealth on other care processes and outcomes were more varied and likely dependent on hospital-level factors. CONCLUSIONS: Telehealth has been used in diverse applications for sepsis care, and it may improve patient outcomes in certain contexts. Additional interventional trials and cost-based analyses would clarify the causal role of telehealth in improving sepsis outcomes.

The use of dexmedetomidine in the emergency department: A systematic review.

BACKGROUND: Dexmedetomidine (DEX), a centrally acting alpha-2 agonist, is increasingly used for sedation in multiple clinical settings. Evidence from the intensive care unit and operative settings suggests DEX may have significant advantages over traditional GABAergic sedatives such as benzodiazepines. There has been limited research on the use of DEX in the emergency department (ED). METHODS: We performed a systematic review of the medical literature to identify all published evidence regarding the use of DEX in the ED. We included randomized and nonrandomized studies and studies reporting any use of DEX in the ED, even when it was not the primary focus of the study. Two authors reviewed studies for inclusion, and a single author assessed studies for quality and risk of bias and abstracted data. RESULTS: We identified 35 studies meeting inclusion criteria, including 11 randomized controlled trials, 13 cohort and other nonrandomized studies, and 11 case reports and case series. Significant heterogeneity in interventions, comparators, indications, and outcomes precluded data pooling and meta-analysis. We found modest evidence that DEX was efficacious in facilitating medical imaging and mixed and limited evidence regarding its efficacy for procedural sedation and sedation of nonintubated medical and psychiatric patients. Our results suggested that DEX is associated with bradycardia and hypotension, which are generally transient and infrequently require medical intervention. CONCLUSIONS: A limited body of generally poor- to moderate-quality evidence suggests that the use of DEX may be efficacious in certain clinical scenarios in the ED and that DEX use in the ED is likely safe. Further high-quality research into DEX use in the ED setting is needed, with a particular focus on clear and consistent selection of indications, identification of clear and clinically relevant primary outcomes, and careful assessment of the clinical implications of the hemodynamic effects of DEX therapy.

Outcomes Associated With Rural Emergency Department Provider-to-Provider Telehealth for Sepsis Care: A Multicenter Cohort Study.

STUDY OBJECTIVE: To test the hypothesis that provider-to-provider tele-emergency department care is associated with more 28-day hospital-free days and improved Surviving Sepsis Campaign (SSC) guideline adherence in rural emergency departments (EDs). METHODS: Multicenter (n=23), propensity-matched, cohort study using medical records of patients with sepsis from rural hospitals in an established, on-demand, rural video tele-ED network in the upper Midwest between August 2016 and June 2019. The primary outcome was 28-day hospital-free days, with secondary outcomes of 28-day inhospital mortality and SSC guideline adherence. RESULTS: A total of 1,191 patients were included in the analysis, with tele-ED used for 326 (27%). Tele-ED cases were more likely to be transferred to another hospital (88% versus 8%, difference 79%, 95% confidence interval [CI] 75% to 83%). After matching and regression adjustment, tele-ED cases did not have more 28-day hospital-free days (difference 0.07 days more for tele-ED, 95% CI -0.04 to 0.17) or 28-day inhospital mortality (adjusted odds ratio [aOR] 0.51, 95% CI 0.16 to 1.60). Adherence with both the SSC 3-hour bundle (aOR 0.59, 95% CI 0.28 to 1.22) and complete bundle (aOR 0.45, 95% CI 0.02 to 11.60) were similar. An a priori-defined subgroup of patients treated by advanced practice providers suggested that the mortality was lower in the cohort with tele-ED use (aOR 0.11, 95% CI 0.02 to 0.73) despite no significant difference in complete SSC bundle adherence (aOR 2.88, 95% CI 0.52 to 15.86). CONCLUSION: Rural emergency department patients treated with provider-to-provider tele-ED care in a mature network appear to have similar clinical outcomes to those treated without.

Temperature Trajectory Subphenotypes in Oncology Patients with Neutropenia and Suspected Infection.

Rationale: Despite etiologic and severity heterogeneity in neutropenic sepsis, management is often uniform. Understanding host response clinical subphenotypes might inform treatment strategies for neutropenic sepsis. Objectives: In this retrospective two-hospital study, we analyzed whether temperature trajectory modeling could identify distinct, clinically relevant subphenotypes among oncology patients with neutropenia and suspected infection. Methods: Among adult oncologic admissions with neutropenia and blood cultures within 24 hours, a previously validated model classified patients' initial 72-hour temperature trajectories into one of four subphenotypes. We analyzed subphenotypes' independent relationships with hospital mortality and bloodstream infection using multivariable models. Measurements and Main Results: Patients (primary cohort n = 1,145, validation cohort n = 6,564) fit into one of four temperature subphenotypes. "Hyperthermic slow resolvers" (pooled n = 1,140 [14.8%], mortality n = 104 [9.1%]) and "hypothermic" encounters (n = 1,612 [20.9%], mortality n = 138 [8.6%]) had higher mortality than "hyperthermic fast resolvers" (n = 1,314 [17.0%], mortality n = 47 [3.6%]) and "normothermic" (n = 3,643 [47.3%], mortality n = 196 [5.4%]) encounters (P < 0.001). Bloodstream infections were more common among hyperthermic slow resolvers (n = 248 [21.8%]) and hyperthermic fast resolvers (n = 240 [18.3%]) than among hypothermic (n = 188 [11.7%]) or normothermic (n = 418 [11.5%]) encounters (P < 0.001). Adjusted for confounders, hyperthermic slow resolvers had increased adjusted odds for mortality (primary cohort odds ratio, 1.91 [P = 0.03]; validation cohort odds ratio, 2.19 [P < 0.001]) and bloodstream infection (primary odds ratio, 1.54 [P = 0.04]; validation cohort odds ratio, 2.15 [P < 0.001]). Conclusions: Temperature trajectory subphenotypes were independently associated with important outcomes among hospitalized patients with neutropenia in two independent cohorts.

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.

The safety and efficacy of push dose vasopressors in critically ill adults.

PURPOSE: To evaluate practice patterns, efficacy, and safety of push dose pressors (PDP) in critically ill patients outside of the operating room (OR) at a large academic medical center. MATERIALS AND METHODS: This was a single-center, retrospective cohort study (June 2018 to July 2020) conducted at a 1273-bed academic medical center. The primary outcome was efficacy, defined as a 25% increase in systolic blood pressure, and the cohort was analyzed according to PDP response (i.e. responders versus non-responders). A logistic regression model was used to assess predictors of response to PDPs. Safety outcomes included the incidence of hypertension, bradycardia, and tachycardia. RESULTS: 1727 patients were included in the final analysis. The median doses of phenylephrine and epinephrine administered were 400 µg (IQR 200-888 µg) and 50 µg (IQR 20-100 µg). The primary outcome was achieved in 102 (71.8%) patients in the epinephrine group and 1140 (55.9%) of patients in the phenylephrine group. Adverse effects after PDP receipt were minimal, with the most common being hypertension in 6.6% and 13.4% of the phenylephrine and epinephrine groups respectively. CONCLUSIONS: This study demonstrates that PDP phenylephrine and epinephrine are safe and efficacious in treating the acute hypotensive period.

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.

Therapeutic Hyperthermia Is Associated With Improved Survival in Afebrile Critically Ill Patients With Sepsis: A Pilot Randomized Trial.

OBJECTIVES: To test the hypothesis that forced-air warming of critically ill afebrile sepsis patients improves immune function compared to standard temperature management. DESIGN: Single-center, prospective, open-label, randomized controlled trial. SETTING: One thousand two hundred-bed academic medical center. PATIENTS: Eligible patients were mechanically ventilated septic adults with: 1) a diagnosis of sepsis within 48 hours of enrollment; 2) anticipated need for mechanical ventilation of greater than 48 hours; and 3) a maximum temperature less than 38.3°C within the 24 hours prior to enrollment. Primary exclusion criteria included: immunologic diseases, immune-suppressing medications, and any existing condition sensitive to therapeutic hyperthermia (e.g., brain injury). The primary outcome was monocyte human leukocyte antigen (HLA)-DR expression, with secondary outcomes of CD3/CD28-induced interferon gamma (IFN-γ) production, mortality, and 28-day hospital-free days. INTERVENTIONS: External warming using a forced-air warming blanket for 48 hours, with a goal temperature 1.5°C above the lowest temperature documented in the previous 24 hours. MEASUREMENTS AND MAIN RESULTS: We enrolled 56 participants in the study. No differences were observed between the groups in HLA-DR expression (692 vs 2,002; p = 0.396) or IFN-γ production (31 vs 69; p = 0.678). Participants allocated to external warming had lower 28-day mortality (18% vs 43%; absolute risk reduction, 25%; 95% CI, 2-48%) and more 28-day hospital-free days (difference, 2.6 d; 95% CI, 0-11.6). CONCLUSIONS: Participants randomized to external forced-air warming did not have a difference in HLA-DR expression or IFN-γ production. In this pilot study, however, 28-day mortality was lower in the intervention group. Future research should seek to better elucidate the impact of temperature modulation on immune and nonimmune organ failure pathways in sepsis.

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.

Posttraumatic stress disorder symptoms after respiratory and cardiovascular emergencies predict risk of hospital readmission: A prospective cohort study.

BACKGROUND: Twenty-five percent of patients presenting to the emergency department (ED) for a respiratory or cardiovascular medical emergency develop clinically significant posttraumatic stress disorder (PTSD) symptoms. It is possible that development of PTSD symptoms in this cohort is associated with subsequent adverse physical health events. Our objective was to test whether clinically significant PTSD symptoms 30 days postdischarge are associated with increased risk for hospital readmission within 24 months after discharge among patients presenting to the ED for a respiratory or cardiovascular emergency. METHODS: This was a prospective cohort study conducted between January 1, 2018, and December 31, 2020, at a U.S. academic medical center, including adult patients presenting with acute respiratory failure or cardiovascular instability requiring a potentially life-sustaining intervention in the ED. PTSD symptoms 30 days postdischarge were measured using the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders-5. The primary outcome was all-cause hospital readmission over the subsequent 24 months after hospital discharge from the index ED visit. RESULTS: Of the 99 patients included, 73% (95% confidence interval [CI] = 63% to 81%) had a hospital readmission within 24 months. In a multivariable Cox proportional hazards model adjusting for potential confounders (e.g., age, severity of illness during index ED visit, preexisting comorbid conditions) presence of clinically significant PTSD symptoms at 30 days was independently associated with increased risk for all-cause hospital readmission at 24 months (hazards ratio = 2.19, 95% CI = 1.30 to 3.69). These results remained statistically significant across multiple sensitivity analyses. CONCLUSIONS: Hospital readmission is common among survivors of acute respiratory failure and cardiovascular instability, and PTSD symptoms 30 days postdischarge are an independent predictor of hospital readmission. Survivors of medical emergencies may warrant follow-up evaluation for PTSD symptoms, and future research is warranted to better understand the relationship between psychological trauma and hospital readmission.

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.

The Use of Dexmedetomidine in the Emergency Department: A Cohort Study.

INTRODUCTION: Management of sedation, analgesia, and anxiolysis are cornerstone therapies in the emergency department (ED). Dexmedetomidine (DEX), a central alpha-2 agonist, is increasingly being used, and intensive care unit (ICU) data demonstrate improved outcomes in patients with respiratory failure. However, there is a lack of ED-based data. We therefore sought to: 1) characterize ED DEX use; 2) describe the incidence of adverse events; and 3) explore factors associated with adverse events among patients receiving DEX in the ED. METHODS: This was a single-center, retrospective, cohort study of consecutive ED patients administered DEX (January 1, 2017-July 1, 2019) at an academic, tertiary care ED with an annual census of ~90,000 patient visits. All included patients (n= 103) were analyzed for characterization of DEX use in the ED. The primary outcome was a composite of adverse events, bradycardia and hypotension. Secondary clinical outcomes included ventilator-, ICU-, and hospital-free days, and hospital mortality. To examine for variables associated with adverse events, we used a multivariable logistic regression model. RESULTS: We report on 103 patients. Dexmedetomidine was most commonly given for acute respiratory failure, including sedation for mechanical ventilation (28.9%) and facilitation of non-invasive ventilation (17.4%). Fifty-four (52.4%) patients experienced the composite adverse event, with hypotension occurring in 41 patients (39.8%) and bradycardia occurring in 18 patients (17.5%). Dexmedetomidine was stopped secondary to an adverse event in eight patients (7.8%). Duration of DEX use in the ED was associated with an increase adverse event risk (adjusted odds ratio, 1.004; 95% confidence interval, 1.001, 1.008). CONCLUSION: Dexmedetomidine is most commonly administered in the ED for patients with acute respiratory failure. Adverse events are relatively common, yet DEX is discontinued comparatively infrequently due to adverse events. Our results suggest that DEX could be a viable option for analgesia, anxiolysis, and sedation in ED patients.