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Supplemental Digital Content is available in the text., OBJECTIVES: To assess the effectiveness of a chaplain patient navigator in improving outcomes and reducing costs in the ICU setting. DESIGN: A randomized controlled trial at a large, urban, academic community hospital in Baltimore, Maryland. SETTING/PATIENTS: All patients admitted to the Johns Hopkins Bayview Medical Center Cardiac and Medical ICUs between March 2015 and December 2015. INTERVENTIONS: Patients in the intervention group were assigned a chaplain patient navigator to facilitate communication, offer support, and setup multidisciplinary family meetings. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were hospital and ICU length of stay. Secondary outcomes included total and ICU charges, 60- and 90-day readmission rates, and the number of palliative care consults. For all outcomes, patients were included in the intention-to-treat analyses only if they remained in the ICU greater than 24 hours. In total, 1,174 were randomly assigned to “usual care” (n = 573) or to the intervention (n = 601). In the intervention group, 44.8% (269/601) had meetings within 24 hours of admission and, of those patients, 32.8% (88/268) took part in the larger multidisciplinary family meeting 2–3 days later. The intervention group had longer mean adjusted hospital length of stay (7.78 vs 8.63 d; p ≤ 0.001) and mean ICU length of stay (3.65 vs 3.87 d; p = 0.029). In addition, they had greater total and ICU charges. There were no differences in other outcomes. Of note, only differences in total and ICU charges remained when controlling for case-mix index, which were greater in the intervention group. CONCLUSIONS: Although the chaplain patient navigator anecdotally enhanced communication, our study found an increase in hospital and ICU length of stay as well as cost. Since other studies have shown benefits in some clinical outcomes, projects focused on patient navigators may learn lessons from our study in order to better prioritize family meetings, gather indicators of communication quality, and identify the optimal patient navigator operational context.

Supplemental Digital Content is available in the text., BACKGROUND: Ischemia-reperfusion injury is common in critically ill patients, and directed therapies are lacking. Inhaled hydrogen gas diminishes ischemia-reperfusion injury in models of shock, stroke, and cardiac arrest. The purpose of this study was to investigate the safety of inhaled hydrogen gas at doses required for a clinical efficacy study. DESIGN: Prospective, single-arm study. SETTING: Tertiary care hospital. PATIENTS/SUBJECTS: Eight healthy adult participants. INTERVENTIONS: Subjects underwent hospitalized exposure to 2.4% hydrogen gas in medical air via high-flow nasal cannula (15 L/min) for 24 (n = 2), 48 (n = 2), or 72 (n = 4) hours. MEASUREMENTS AND MAIN RESULTS: Endpoints included vital signs, patient- and nurse-reported signs and symptoms (stratified according to clinical significance), pulmonary function testing, 12-lead electrocardiogram, mini-mental state examinations, neurologic examination, and serologic testing prior to and following exposure. All adverse events were verified by two clinicians external to the study team and an external Data and Safety Monitoring Board. All eight participants (18–30 yr; 50% female; 62% non-Caucasian) completed the study without early termination. No clinically significant adverse events occurred in any patient. Compared with baseline measures, there were no clinically significant changes over time in vital signs, pulmonary function testing results, Mini-Mental State Examination scores, neurologic examination findings, electrocardiogram measurements, or serologic tests for hematologic (except for clinically insignificant increases in hematocrit and platelet counts), renal, hepatic, pancreatic, or cardiac injury associated with hydrogen gas inhalation. CONCLUSIONS: Inhalation of 2.4% hydrogen gas does not appear to cause clinically significant adverse effects in healthy adults. Although these data suggest that inhaled hydrogen gas may be well tolerated, future studies need to be powered to further evaluate safety. These data will be foundational to future interventional studies of inhaled hydrogen gas in injury states, including following cardiac arrest.

Supplemental Digital Content is available in the text., OBJECTIVES: To compare the performance of Sequential Organ Failure Assessment, systemic inflammatory response syndrome, Red Flag Sepsis, and National Institute of Clinical Excellence sepsis risk stratification tools in the identification of patients at greatest risk of mortality from sepsis in nonintensive care environments. DESIGN: Secondary analysis of three annual 24-hour point-prevalence study periods. SETTING: The general wards and emergency departments of 14 acute hospitals across Wales. Studies were conducted on the third Wednesday of October in 2017, 2018, and 2019. PATIENTS: We screened all patients presenting to the emergency department and on the general wards. MEASUREMENTS AND MAIN RESULTS: We recruited 1,271 patients, of which 724 (56.9%) had systemic inflammatory response syndrome greater than or equal to 2, 679 (53.4%) had Sequential Organ Failure Assessment greater than or equal to 2, and 977 (76.9%) had Red Flag Sepsis. When stratified according to National Institute of Clinical Excellence guidelines, 450 patients (35.4%) were in the “High risk” category in comparison with 665 (52.3%) in “Moderate to High risk” and 156 (12.3%) in “Low risk” category. In a planned sensitivity analysis, we found that none of the tools accurately predicted mortality at 90 days, and Sequential Organ Failure Assessment and National Institute of Clinical Excellence tools showed only moderate discriminatory power for mortality at 7 and 14 days. Furthermore, we could not find any significant correlation with any of the tools at any of the mortality time points. CONCLUSIONS: Our data suggest that the sepsis risk stratification tools currently utilized in emergency departments and on the general wards do not predict mortality adequately. This is illustrated by the disparity in mortality risk of the populations captured by each instrument, as well as the weak concordance between them. We propose that future studies on the development of sepsis identification tools should focus on identifying predicator values of both the short- and long-term outcomes of sepsis.

Supplemental Digital Content is available in the text., Objectives: To prospectively describe 1-year outcomes, with a focus on functional outcome, cognitive outcome, and the burden of anxiety, depression, and post-traumatic stress disorder, in coronavirus disease 2019 patients managed with extracorporeal membrane oxygenation. Design: Prospective case series. Setting: Tertiary extracorporeal membrane oxygenation center in the United States. Patients: Adult coronavirus disease 2019 acute respiratory distress syndrome patients managed with extracorporeal membrane oxygenation March 1, 2020, to July 31, 2020. Interventions: Baseline variables, treatment measures, and short-term outcomes were obtained from the medical record. Survivors were interviewed by telephone, a year following the index intensive care admission. Functional outcome was assessed using the modified Rankin Scale and the World Health Organization Disability Assessment Scale 2.0. Cognitive status was assessed with the 5-minute Montreal Cognitive Assessment. The Hospital Anxiety and Depression Scale was used to screen for anxiety and depression. Screening for post-traumatic stress disorder was performed with the Posttraumatic Stress Disorder Checklist 5 instrument. Measurements and Main Results: Twenty-three patients were managed with extracorporeal membrane oxygenation, 14 (61%) survived to hospital discharge. Thirteen (57%) were alive at 1 year. One patient was dependent on mechanical ventilation, another intermittently required supplemental oxygen at 1 year. The median modified Rankin Scale score was 2 (interquartile range, 1–2), median World Health Organization Disability Assessment Scale 2.0 impairment score was 21% (interquartile range, 6–42%). Six of 12 previously employed individuals (50%) had returned to work, and 10 of 12 (83%) were entirely independent in activities of daily living. The median Montreal Cognitive Assessment score was 14 (interquartile range, 13–14). Of 10 patients assessed with Hospital Anxiety and Depression Scale, 4 (40%) screened positive for depression and 6 (60%) for anxiety. Four of 10 (40%) screened positive for post-traumatic stress disorder. Conclusions: Functional impairment was common a year following the use of extracorporeal membrane oxygenation in coronavirus disease 2019, although the majority achieved independence in daily living and about half returned to work. Long-term anxiety, depression, and post-traumatic stress disorder were common, but cognitive impairment was not.

Supplemental Digital Content is available in the text., OBJECTIVES: We hypothesized that low serum albumin would contribute to pulmonary edema formation, thereby independently increasing the risk of developing acute respiratory distress syndrome in critically ill patients. DESIGN: Retrospective analysis of prospective cohort. SETTING: Medical, surgical, and cardiovascular ICUs at Vanderbilt University Medical Center. PATIENTS: Patients (n = 993) with serum albumin measured for clinical reasons within 24 hours of study enrollment on ICU day 2 were included. MEASUREMENTS AND MAIN RESULTS: The primary outcome was presence of acute respiratory distress syndrome at any time during the first 4 days in the ICU, as defined by the Berlin definition. Secondary outcomes included ventilator-free days and ICU length of stay. In an unadjusted analysis, lower serum albumin levels were associated with a higher occurrence rate of acute respiratory distress syndrome (p < 0.001). In a multivariable analysis controlling for prespecified confounders, lower serum albumin was independently associated with an increased risk of acute respiratory distress syndrome (odds ratio, 1.48 per 1-g/dL decrease in albumin; 95% CI, 1.14–1.94; p = 0.004). Additionally, lower serum albumin was associated with increased mortality (odds ratio, 1.56 per 1-g/dL decrease in albumin; 95% CI, 1.19–2.04; p = 0.001), increased ICU length of stay (incidence rate ratio, 1.19; 95% CI, 1.15–1.23; p < 0.001), higher Sequential Organ Failure Assessment score (p < 0.001), and fewer ventilator-free days (incidence rate ratio, 1.21; 95% CI, 1.19–1.24; p < 0.001). CONCLUSIONS: Among adult ICU patients, lower serum albumin was independently associated with increased risk of acute respiratory distress syndrome after controlling for severity of illness and potential confounders. These findings support the hypothesis that low plasma oncotic pressure contributes to pulmonary edema formation in patients at risk for acute respiratory distress syndrome, independent of severity of illness.

Supplemental Digital Content is available in the text., OBJECTIVES: Patients with aneurysmal subarachnoid hemorrhage (ruptured brain aneurysm) often have reduced health-related quality of life at follow-up in multiple domains (e.g., cognitive function and social function). We tested the hypothesis that there are distinct patterns of patient outcomes across domains of health-related quality of life, “complex patient outcomes,” in survivors of subarachnoid hemorrhage. DESIGN: Patients with subarachnoid hemorrhage were prospectively identified. Clinical data were prospectively recorded. Health-related quality of life was prospectively assessed at 3-month follow-up using the National Institutes of Health Patient Reported Outcomes Measurement Information System and neuro-quality of life in the domains of mobility, cognitive function, satisfaction with social roles, and depression. We used k-means clustering to analyze prospectively recorded health-related quality of life data, identifying clusters of complex patient outcomes. Decision tree analysis identified index hospital stay factors predictive of a patient having a particular complex patient outcome at follow-up. SETTING: Academic medical center. PATIENTS: One hundred three survivors of subarachnoid hemorrhage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 103 patients, of whom 75 (72.8%) were female, and mean age was 53.6 ± 13.4 years. There were three complex patient outcomes: health-related quality of life greater than 1 sd better than the U.S. mean across all domains (n = 23, 22.3%), health-related quality of life greater than 1 sd worse than U.S. mean across all domains (n = 26, 25.2%), and satisfaction with social roles greater than 0.5 sd worse than U.S. mean with cognitive function, depression, and mobility scores near the U.S. mean (n = 54, 52.4%). In decision tree analysis, hospital disposition and Hunt and Hess Grade were associated with complex patient outcome. CONCLUSIONS: Complex patient outcomes across multiple domains of health-related quality of life at follow-up after subarachnoid hemorrhage are distinct and may be predictable.

Supplemental Digital Content is available in the text., OBJECTIVES: Examine the safety and feasibility of a multimodal in-person or telehealth treatment program, administered in acute recovery phase for patients surviving critical coronavirus disease 2019. DESIGN: Pragmatic, pre-post, nonrandomized controlled trial with patients electing enrollment into one of the two recovery pathways. SETTING: ICU Recovery Clinic in an academic medical center. PATIENTS: Adult patients surviving acute respiratory failure due to critical coronavirus disease 2019. INTERVENTIONS: Patients participated in combined ICU Recovery clinic and 8 weeks of physical rehabilitation delivered: 1) in-person or 2) telehealth. Patients received medical care by an ICU Recovery Clinic interdisciplinary team and physical rehabilitation focused on aerobic, resistance, and respiratory muscle training. MEASUREMENTS AND MAIN RESULTS: Thirty-two patients enrolled with mean age 57 ± 12, 62% were male, and the median Sequential Organ Failure Assessment score was 9.5. There were no differences between the two groups except patients in telehealth pathway (n = 10) lived further from clinic than face-to-face patients (162 ± 60 vs 31 ± 47 kilometers, t = 6.06, p < 0.001). Four safety events occurred: one minor adverse event in the telehealth group, two minor adverse events, and one major adverse event in the in-person group. Three patients did not complete the study (two in-person and one telehealth). Six-minute walk distance increased to 101 ± 91 meters from pre to post (n = 29, t = 6.93, p < 0.0001), which was similar between the two groups (110 vs 80 meters, t = 1.34, p = 0.19). Self-reported levels of anxiety, depression, and distress were high in both groups with similar self-report quality of life. CONCLUSIONS: A multimodal treatment program combining care from an interdisciplinary team in an ICU Recovery Clinic with physical rehabilitation is safe and feasible in patients surviving the ICU for coronavirus disease 2019 acute respiratory failure.

Supplemental Digital Content is available in the text., OBJECTIVES: Psychologic sequelae after critical illness, part of the postintensive care syndrome, significantly decrease quality of life. A robustly effective treatment intervention is currently lacking. Virtual reality has beneficial effects on several non-ICU–related psychologic disorders. The aim of this study was to explore patient-related determinants of ICU-specific virtual reality, such as the timing of patients’ self-reported readiness to initiate virtual reality and the number of desired sessions and safety, and to explore the effects of ICU-specific virtual reality on mental health. DESIGN: A multicenter, randomized controlled feasibility study. SETTING: ICU at a university teaching hospital and a secondary care hospital in Rotterdam, The Netherlands. PATIENTS: Consecutive mechanically ventilated patients with sepsis or septic shock. INTERVENTIONS: Patients were randomly assigned (1:1) to receive ICU-specific virtual reality (ICU-specific virtual reality group) or exposure to a nature virtual reality environment (control virtual reality group). MEASUREMENT AND MAIN RESULTS: Explorative outcomes were feasibility, in terms of patient-related determinants, and safety. The effects of ICU-specific virtual reality on the psychologic components of postintensive care syndrome and quality of life were additionally studied. Fifty patients (median age: 61 yr; 21 [42%] female) were included. Patients in the ICU-specific virtual reality group felt ready to initiate the virtual reality intervention 10 days (median, 95% range, 5–21 d) after ICU discharge, and one session (median, 95% range, 1–6) was desired. ICU-specific virtual reality patients experienced higher immersion, cybersickness scores were low, and no changes in vital signs were observed. They also reported reduced posttraumatic stress disorder and depression scores and better mental health from 2 days until 1 month after initial exposure (Short Form-12 Mental Component Scale: ICU-specific virtual reality, 57 [36–67] vs control virtual reality, 47 [26–63]; p < 0.01). Six months after exposure, this effect was still present for posttraumatic stress disorder and depression, but not for mental quality of life. CONCLUSIONS: ICU-specific virtual reality is a feasible and acceptable novel intervention that could be used during recovery from an episode of critical illness in the ICU. A future, adequately powered study should confirm whether virtual reality is able to improve mental health and quality of life.

Supplemental Digital Content is available in the text., OBJECTIVES: Unbiased global metabolomic profiling has not been used to identify distinct subclasses in patients with early sepsis and sepsis-associated acute respiratory distress syndrome. In this study, we examined whether the plasma metabolome reflects systemic illness in early sepsis and in acute respiratory distress syndrome. DESIGN: Plasma metabolites were measured in subjects with early sepsis. SETTING: Patients were admitted from the emergency department to the ICU in a plasma sample collected within 24 hours of ICU admission. Metabolic profiling of 970 metabolites was performed by Metabolon (Durham, NC). Hierarchical clustering and partial least squares discriminant clustering were used to identify distinct clusters among patients with early sepsis and sepsis-associated acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among critically ill patients with early sepsis (n = 197), three metabolically distinct subgroups were identified, with metabolic subtype driven by plasma lipids. Group 1, with 45 subjects (23% of cohort), had increased 60-day mortality (odds ratio, 2; 95% CI, 0.99–4.0; p = 0.04 for group 1 vs all others). This group also had higher rates of vasopressor-dependent shock, acute kidney injury, and met Berlin acute respiratory distress syndrome criteria more often (all p < 0.05). Conversely, metabolic group 3, with 76 subjects (39% of cohort), had the lowest risk of 60-day mortality (odds ratio, 0.44; 95% CI, 0.22–0.86; p = 0.01) and lower rates of organ dysfunction as reflected in a lower Simplified Acute Physiology Score II (p < 0.001). In contrast, global metabolomic profiling did not separate patient with early sepsis with moderate-to-severe acute respiratory distress syndrome (n = 78) from those with sepsis without acute respiratory distress syndrome (n = 75). CONCLUSIONS: Plasma metabolomic profiling in patients with early sepsis identified three metabolically distinct groups that were characterized by different plasma lipid profiles, distinct clinical phenotypes, and 60-day mortality. Plasma metabolites did not distinguish patients with early sepsis who developed acute respiratory distress syndrome from those who did not.

Supplemental Digital Content is available in the text., OBJECTIVES: Hyper- and hypoinflammatory subphenotypes discovered in patients with acute respiratory distress syndrome predict clinical outcomes and therapeutic responses. These subphenotypes may be important in broader critically ill patient populations with acute respiratory failure regardless of clinical diagnosis. We investigated subphenotyping with latent class analysis in an inclusive population of acute respiratory failure, derived a parsimonious model for subphenotypic predictions based on a small set of variables, and examined associations with clinical outcomes. DESIGN: Prospective, observational cohort study. SETTING: Single-center, academic medical ICU. PATIENTS: Mechanically ventilated patients with acute respiratory failure. MEASUREMENTS AND MAIN RESULTS: We included 498 patients with acute respiratory failure (acute respiratory distress syndrome: 143, at-risk for acute respiratory distress syndrome: 198, congestive heart failure: 37, acute on chronic respiratory failure: 23, airway protection: 61, and multifactorial: 35) in our derivation cohort and measured 10 baseline plasma biomarkers. Latent class analysis considering clinical variables and biomarkers determined that a two-class model offered optimal fit (23% hyperinflammatory subphenotype). Distribution of hyperinflammatory subphenotype varied among acute respiratory failure etiologies (acute respiratory distress syndrome: 31%, at-risk for acute respiratory distress syndrome: 27%, congestive heart failure: 22%, acute on chronic respiratory failure 0%, airway protection: 5%, and multifactorial: 14%). Hyperinflammatory patients had higher Sequential Organ Failure Assessment scores, fewer ventilator-free days, and higher 30- and 90-day mortality (all p < 0.001). We derived a parsimonious model consisting of angiopoietin-2, soluble tumor necrosis factor receptor-1, procalcitonin, and bicarbonate and classified subphenotypes in a validation cohort (n = 139). Hyperinflammatory patients (19%) demonstrated higher levels of inflammatory biomarkers not included in the model (p < 0.01) and worse outcomes. CONCLUSIONS: Host-response subphenotypes are observable in a heterogeneous population with acute respiratory failure and predict clinical outcomes. Simple, biomarker-based models can offer prognostic enrichment in patients with acute respiratory failure. The differential distribution of subphenotypes by specific etiologies of acute respiratory failure indicates that subphenotyping may be more relevant in patients with hypoxemic causes of acute respiratory failure and not in patients intubated for airway protection or acute on chronic decompensation.

Supplemental Digital Content is available in the text., OBJECTIVES: To quantify short- and long-term psychologic distress, that is, symptoms of posttraumatic stress disorder, anxiety, and depression, and the health-related quality of life in coronavirus disease 2019 ICU survivors. DESIGN: A prospective, observational cohort study. SETTING: Postcoronavirus disease 2019 clinics of three hospitals in Rotterdam, the Netherlands. PATIENTS: Adult patients admitted for coronavirus disease 2019 to the ICU, who visited the postcoronavirus disease 2019 follow-up clinic. MEASURES AND MAIN RESULTS: The primary outcomes were psychologic distress and overall and mental health-related quality of life, assessed using the Impact of Event Scale-Revised, Hospital Anxiety and Depression Scale, Short-Form 36, and European Quality of Life 5D, 6 weeks, 3 months, and 6 months post hospital discharge. Second, we compared 3-month psychologic and mental health-related quality of life outcomes with a historical critical illness survivor cohort and overall and mental health-related quality of life with the Dutch population. We included 118 patients with a median age of 61 years (95% range, 36–77 yr) of whom 79 (68%) were male. At 6 weeks, 13 patients (23%) reported psychologic distress, copresence of probable psychiatric disorders was common, and no decline in psychologic distress was observed throughout follow-up. Coronavirus disease 2019 patients tend to suffer less from posttraumatic stress disorder and reported less severe symptoms of anxiety (Hospital Anxiety and Depression Scale Anxiety Score: 3 [0–17] vs 5 [0–16]; estimated mean difference 2.3 [95% CI, 0.0–4.7]; p = 0.05) and depression (Hospital Anxiety and Depression Scale Depression Score: 3 [0–15] vs 5 [0–16]; estimated mean difference 2.4 [95% CI, 0.1–2.4]; p = 0.04) than the historical critical illness cohort. Overall and mental health-related quality of life increased over time. Coronavirus disease 2019 ICU survivors reported better mental health-related quality of life than our historical cohort, but overall and mental health-related quality of life was still poorer than the Dutch population. CONCLUSIONS: Psychologic distress was common in coronavirus disease 2019 ICU survivors and remained similar until 6 months after hospital discharge. Health-related quality of life increased over time and was higher than in a historical cohort, but was lower than in the Dutch population. Our findings highlight that coronavirus disease 2019 ICU survivors should be monitored after ICU treatment to detect possible psychologic distress.

Supplemental Digital Content is available in the text., OBJECTIVES: Critically ill patients with coronavirus disease 2019 have variable mortality. Risk scores could improve care and be used for prognostic enrichment in trials. We aimed to compare machine learning algorithms and develop a simple tool for predicting 28-day mortality in ICU patients with coronavirus disease 2019. DESIGN: This was an observational study of adult patients with coronavirus disease 2019. The primary outcome was 28-day inhospital mortality. Machine learning models and a simple tool were derived using variables from the first 48 hours of ICU admission and validated externally in independent sites and temporally with more recent admissions. Models were compared with a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 using the area under the receiver operating characteristic curve and calibration. SETTING: Sixty-eight U.S. ICUs. PATIENTS: Adults with coronavirus disease 2019 admitted to 68 ICUs in the United States between March 4, 2020, and June 29, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study included 5,075 patients, 1,846 (36.4%) of whom died by day 28. eXtreme Gradient Boosting had the highest area under the receiver operating characteristic curve in external validation (0.81) and was well-calibrated, while k-nearest neighbors were the lowest performing machine learning algorithm (area under the receiver operating characteristic curve 0.69). Findings were similar with temporal validation. The simple tool, which was created using the most important features from the eXtreme Gradient Boosting model, had a significantly higher area under the receiver operating characteristic curve in external validation (0.78) than the Sequential Organ Failure Assessment score (0.69), National Early Warning Score (0.60), and CURB-65 (0.65; p < 0.05 for all comparisons). Age, number of ICU beds, creatinine, lactate, arterial pH, and Pao2/Fio2 ratio were the most important predictors in the eXtreme Gradient Boosting model. CONCLUSIONS: eXtreme Gradient Boosting had the highest discrimination overall, and our simple tool had higher discrimination than a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 on external validation. These models could be used to improve triage decisions and clinical trial enrichment.

OBJECTIVES:. Extracorporeal membrane oxygenator support is a powerful clinical tool that is currently enjoying a resurgence in popularity. Wider use of extracorporeal membrane oxygenator support is limited by its significant risk profile and extreme consumption of resources. This study examines the role of markers of liver dysfunction in predicting outcomes of adult patients requiring extracorporeal membrane oxygenator support. DESIGN:. Retrospective review. SETTING:. Large extracorporeal membrane oxygenator center, Chicago, IL. PATIENTS:. This study reports a single institution experience examining all adult patients for whom extracorporeal membrane oxygenator support was used over an 8-year period. Data were collected regarding patient demographics, details of extracorporeal membrane oxygenator support provided, laboratory data, and outcomes. Trends in liver function were examined for their ability to predict survival. INTERVENTION:. Extracorporeal membrane oxygenator support, critical care. MEASUREMENTS AND MAIN RESULTS:. Mean age was 50 years (range, 19–82 yr). There were 86 male patients (56.6%) and 66 female patients (43.4%). Indications for initiation of extracorporeal membrane oxygenator support included cardiac 76 patients (50.0%), respiratory 48 patients (31.6%), extracorporeal cardiopulmonary resuscitation 21 patients (13.3%), and combined cardiac/respiratory seven patients (4.6%). Mean duration of extracorporeal membrane oxygenator support was 17 days (range 1–223 d) or median 8 days (interquartile range, 4–17 d). Overall, in-hospital mortality was 56% (86/152). Forty-five percent of adult patients (68/152) surpassed at least one of the following established liver dysfunction thresholds: total bilirubin greater than 15 mg/dL, aspartate aminotransferase greater than 20× upper limit of normal, and alanine aminotransferase greater than 20× upper limit of normal. The multivariable logistic analysis yielded three significant findings associated with in-hospital mortality: highest total bilirubin greater than 15 (adjusted odds ratio = 4.40; 95% CI, 1.19–21.87; p = 0.04), age (adjusted odds ratio = 1.03; 95% CI, 1.00–1.05; p = 0.04), and highest lactate (adjusted odds ratio = 1.15; 95% CI, 1.06–1.26; p = 0.002). CONCLUSIONS:. Increases in age, highest total bilirubin, and lactate all correlated with in-hospital mortality in multivariable analysis of patients requiring extracorporeal membrane oxygenator support.

OBJECTIVES:. Family members commonly have inaccurate expectations of patient’s prognosis in ICU. Adding to classic oral information, a visual support, depicting day by day the evolution of the condition of the patient, improves the concordance in prognosis estimate between physicians and family members. The objective of this study was to evaluate the impact of this tool on symptoms of anxiety/depression of family members. DESIGN:. Bicenter prospective before-and-after study. SETTING:. A nonacademic and a university hospital. SUBJECTS:. Relatives of consecutive patients admitted in the two ICUs. INTERVENTIONS:. In the period “before,” family members received classic oral information, and in the period “after,” they could consult the visual support in the patient’s room. The primary endpoint was the Hospital Anxiety and Depression Scale score of relatives at day 5. Secondary outcomes were the prevalence of symptoms of anxiety (Hospital Anxiety and Depression Scale anxiety subscale score > 7) and depression (Hospital Anxiety and Depression Scale depression subscale score > 7) at day 5 and Hospital Anxiety and Depression Scale score at day 90. MEASUREMENTS AND MAIN RESULTS:. A total of 140 patients and their referent family members were included (77 in period before and 63 after). Characteristics of patients of the two groups were similar regarding age, reason for admission, Simplified Acute Physiology Score II at admission, and Sequential Organ Failure Assessment score at day 5. At day 5, median Hospital Anxiety and Depression Scale score was 17 (9–25) before and 15 (10–22) after the implementation of the visual support (p = 0.43). The prevalence of symptoms of anxiety and depression was similar in the two groups (66.2% and 49.4% before and 68.3% and 36.5% after [not significant], respectively). At day 90, median Hospital Anxiety and Depression Scale score was 11 before (7–16) and 9 (5–16) after the implementation of the tool (p = 0.38). CONCLUSIONS:. In this study, the use of a visual support tool dedicated to prognosis did not modify the level of stress of family members.

Supplemental Digital Content is available in the text., OBJECTIVES: To evaluate the link between early acute respiratory failure and functional morbidity in survivors using the plasma biomarkers interleukin-8, interleukin-1 receptor antagonist, thrombomodulin, and plasminogen activator inhibitor-1. We hypothesized that children with acute respiratory failure with higher levels of inflammation would have worse functional outcomes at discharge, as measured by Pediatric Overall Performance Category. DESIGN: Secondary analysis of the Genetic Variation and Biomarkers in Children with Acute Lung Injury (R01HL095410) study. SETTING: Twenty-two PICUs participating in the multisite clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (U01 HL086622) and the ancillary study (Biomarkers in Children with Acute Lung Injury). SUBJECTS: Children 2 weeks to 17 years requiring invasive mechanical ventilation for acute airways and/or parenchymal lung disease. Patients with an admission Pediatric Overall Performance Category greater than 3 (severe disability, coma, or brain death) were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among survivors, 387 patients had no worsening of Pediatric Overall Performance Category at discharge while 40 had worsening functional status, defined as any increase in Pediatric Overall Performance Category from baseline. There was no significant relationship between worsening of Pediatric Overall Performance Category and interleukin-8 or plasminogen activator inhibitor-1 on any day. There was no significant relationship between interleukin-1 receptor antagonist, or thrombomodulin, and worsening Pediatric Overall Performance Category on day 1. Plasma interleukin-1 receptor antagonist and thrombomodulin were significantly elevated on days 2 and 3 in those with worse functional status at discharge compared with those without. In multivariable analysis, interleukin-1 receptor antagonist and thrombomodulin were associated with a decline in functional status on days 2 and 3 after adjustment for age and highest oxygenation index. However, after adjusting for age and cardiovascular failure, only day 2 thrombomodulin levels were associated with a worsening in Pediatric Overall Performance Category. CONCLUSIONS: Higher levels of interleukin-1 receptor antagonist or thrombomodulin following intubation were associated with worse Pediatric Overall Performance Category scores at hospital discharge in children who survive acute respiratory failure. These data suggest that persistent inflammation may be related to functional decline.

OBJECTIVES:. We sought to validate prognostic scores in coronavirus disease 2019 including National Early Warning Score, Modified Early Warning Score, and age-based modifications, and define their performance characteristics. DESIGN:. We analyzed prospectively collected data from the Adaptive COVID-19 Treatment Trial. National Early Warning Score was collected daily during the trial, Modified Early Warning Score was calculated, and age applied to both scores. We assessed prognostic value for the end points of recovery, mechanical ventilation, and death for score at enrollment, average, and slope of score over the first 48 hours. SETTING:. A multisite international inpatient trial. PATIENTS:. A total of 1,062 adult nonpregnant inpatients with severe coronavirus disease 2019 pneumonia. INTERVENTIONS:. Adaptive COVID-19 Treatment Trial 1 randomized participants to receive remdesivir or placebo. The prognostic value of predictive scores was evaluated in both groups separately to assess for differential performance in the setting of remdesivir treatment. MEASUREMENTS AND MAIN RESULTS:. For mortality, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.60–0.68), and improved with addition of age (c-index, 0.66–0.74). For recovery, baseline National Early Warning Score and Modified Early Warning Score demonstrated somewhat better prognostic ability (c-index, 0.65–0.69); however, National Early Warning Score+age and Modified Early Warning Score+age further improved performance (c-index, 0.68–0.71). For deterioration, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.59–0.69) and improved with addition of age (c-index, 0.63–0.70). All prognostic performance improvements due to addition of age were significant (p < 0.05). CONCLUSIONS:. In the Adaptive COVID-19 Treatment Trial 1 cohort, National Early Warning Score and Modified Early Warning Score demonstrated moderate prognostic performance in patients with severe coronavirus disease 2019, with improvement in predictive ability for National Early Warning Score+age and Modified Early Warning Score+age. Area under receiver operating curve for National Early Warning Score and Modified Early Warning Score improved in patients receiving remdesivir versus placebo early in the pandemic for recovery and mortality. Although these scores are simple and readily obtainable in myriad settings, in our data set, they were insufficiently predictive to completely replace clinical judgment in coronavirus disease 2019 and may serve best as an adjunct to triage, disposition, and resourcing decisions.

Supplemental Digital Content is available in the text., OBJECTIVES: To measure the frequency of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis among decedents in hospitals of different sizes and teaching statuses. DESIGN: We performed a multicenter, retrospective cohort study. SETTING: Four large teaching hospitals, four affiliated small teaching hospitals, and nine affiliated nonteaching hospitals in the United States. PATIENTS: We included a sample of all adult inpatient decedents between August 2017 and August 2019. MEASUREMENTS AND MAIN RESULTS: We reviewed inpatient notes and categorized the immediately preceding circumstances as withdrawal of life-sustaining therapy for perceived poor neurologic prognosis, withdrawal of life-sustaining therapy for nonneurologic reasons, limitations or withholding of life support or resuscitation, cardiac death despite full treatment, or brain death. Of 2,100 patients, median age was 71 years (interquartile range, 60–81 yr), median hospital length of stay was 5 days (interquartile range, 2–11 d), and 1,326 (63%) were treated at four large teaching hospitals. Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis occurred in 516 patients (25%) and was the sole contributing factor to death in 331 (15%). Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis was common in all hospitals: 30% of deaths at large teaching hospitals, 19% of deaths in small teaching hospitals, and 15% of deaths at nonteaching hospitals. Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis happened frequently across all hospital units. Withdrawal of life-sustaining therapy for perceived poor neurologic prognosis contributed to one in 12 deaths in patients without a primary neurologic diagnosis. After accounting for patient and hospital characteristics, significant between-hospital variability in the odds of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis persisted. CONCLUSIONS: A quarter of inpatient deaths in this cohort occurred after withdrawal of life-sustaining therapy for perceived poor neurologic prognosis. The rate of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis occurred commonly in all type of hospital settings. We observed significant unexplained variation in the odds of withdrawal of life-sustaining therapy for perceived poor neurologic prognosis across participating hospitals.

Supplemental Digital Content is available in the text., OBJECTIVES: To determine methylprednisolone’s dose, duration, and administration from onset of symptoms and association with 60 days in hospital survival of coronavirus disease 2019 pneumonia. DESIGN: Cohort study. SETTING: Thirteen hospitals in New Jersey, United States during March to June 2020. PATIENTS: Seven-hundred fifty-nine hospitalized coronavirus disease 2019 patients. INTERVENTIONS: We performed a propensity matched cohort study between patients who received methylprednisolone and no methylprednisolone. Patients in the methylprednisolone group were further differentiated into dose (high dose and low dose), duration, and administration from onset of symptoms. MEASUREMENTS AND MAIN RESULTS: In the propensity matched sample, 99 out of 380 (26%) in no methylprednisolone, 69 out of 215 (31.9%) in low-dose methylprednisolone, and 74 out of 164 (55.2%) high-dose methylprednisolone expired. Overall median survival for no methylprednisolone (25.0 d), low-dose methylprednisolone (39.0 d), high-dose methylprednisolone (20.0 d), less than or equal to 7 days duration (19.0 d), 7–14 days duration (30.0 d), greater than 14 days duration (44.0 d), onset of symptoms less than or equal to 7 days (20.0 d), and onset of symptoms 7–14 days (27.0 d) were statistically significant (log-rank p ≤ 0.001). Multivariate Cox regression showed nursing home residents, coronary artery disease, and invasive mechanical ventilation were independently associated with mortality. Methylprednisolone was associated with reduced mortality compared with no methylprednisolone (hazard ratio, 0.40; 95% CI, 0.27–0.59; p < 0.001) but no added benefit with high dose. Low-dose methylprednisolone for 7–14 days was associated with reduced mortality compared with less than or equal to 7 days (hazard ratio, 0.45; 95% CI, 0.22–0.91; p = 0.0273), and no additional benefit if greater than 14 days (hazard ratio, 1.27; 95% CI, 0.60–2.69; p = 0.5434). Combination therapy with tocilizumab was associated with reduced mortality over monotherapy (p < 0.0116). CONCLUSIONS: Low-dose methylprednisolone was associated with reduced mortality if given greater than 7 days from onset of symptoms, and no additional benefit greater than 14 days. High dose was associated with higher mortality.

Supplemental Digital Content is available in the text., OBJECTIVES: Clinicians have little guidance on the time needed before assessing the effect of a mean airway pressure change during high-frequency oscillatory ventilation. We aimed to determine: 1) time to stable lung volume after a mean airway pressure change during high-frequency oscillatory ventilation and 2) the relationship between time to volume stability and the volume state of the lung. DESIGN: Prospective observational study. SETTING: Regional quaternary teaching hospital neonatal ICU. PATIENTS: Thirteen term or near-term infants receiving high-frequency oscillatory ventilation and muscle relaxants. INTERVENTIONS: One to two cm H2O mean airway pressure changes every 10 minutes as part of an open lung strategy based on oxygen response. MEASUREMENTS AND MAIN RESULTS: Continuous lung volume measurements (respiratory inductive plethysmography) were made during the mean airway pressure changes. Volume signals were analyzed with a biexponential model to calculate the time to stable lung volume if the model R2 was greater than 0.6. If volume stability did not occur within 10 minutes, the model was extrapolated to maximum 3,600 s. One-hundred ninety-six mean airway pressure changes were made, with no volume change in 33 occurrences (17%). One-hundred twenty-five volume signals met modeling criteria for inclusion; median (interquartile range) R2, 0.96 (0.91–0.98). The time to stable lung volume was 1,131 seconds (718–1,959 s) (mean airway pressure increases) and 647 seconds (439–1,309 s) (mean airway pressure decreases), with only 17 (14%) occurring within 10 minutes and time to stability being longer when the lung was atelectatic. CONCLUSIONS: During high-frequency oscillatory ventilation, the time to stable lung volume after a mean airway pressure change is variable, often requires more than 10 minutes, and is dependent on the preceding volume state.

Supplemental Digital Content is available in the text., OBJECTIVES: To investigate the association between plasma sodium concentrations and 6-month neurologic outcome in critically ill patients with aneurysmal subarachnoid hemorrhage. DESIGN: Prospective cohort study. SETTING: Eleven ICUs in Australia and New Zealand. PARTICIPANTS: Three-hundred fifty-six aneurysmal subarachnoid hemorrhage patients admitted to ICU between March 2016 and June 2018. The exposure variable was daily measured plasma sodium. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six-month neurologic outcome as measured by the modified Rankin Scale. A poor outcome was defined as a modified Rankin Scale greater than or equal to 4. The mean age was 57 years (± 12.6 yr), 68% were female, and 32% (n = 113) had a poor outcome. In multivariable analysis, including age, illness severity, and process of care measures as covariates, higher mean sodium concentrations (odds ratio, 1.17; 95% CI, 1.05–1.29), and greater overall variability—as measured by the sd (odds ratio, 1.53; 95% CI, 1.17–1.99)—were associated with a greater likelihood of a poor outcome. Multivariable generalized additive modeling demonstrated, specifically, that a high initial sodium concentration, followed by a gradual decline from day 3 onwards, was also associated with a poor outcome. Finally, greater variability in sodium concentrations was associated with a longer ICU and hospital length of stay: mean ICU length of stay ratio (1.13; 95% CI, 1.07–1.20) and mean hospital length of stay ratio (1.08; 95% CI, 1.01–1.15). CONCLUSIONS: In critically ill aneurysmal subarachnoid hemorrhage patients, higher mean sodium concentrations and greater variability were associated with worse neurologic outcomes at 6 months, despite adjustment for known confounders. Interventional studies would be required to demonstrate a causal relationship.

Supplemental Digital Content is available in the text., Objectives: To compare patient management and outcome during the first and second waves of the coronavirus 2019 pandemic. Design: Single-center prospective cohort study. Setting: Tertiary-care University Hospital. Patients: All adult patients admitted in either the first (from March 15 to May 15, 2020) or second (from October 1 to November 30, 2020) wave of coronavirus disease 2019. Interventions: None. Measurements and Main Results: Primary outcome was 30-day mortality. During the second wave of the coronavirus disease 2019 pandemic, 33 patients (4.8%) were transferred due to overcrowding and excluded from analysis. There were 341 (first wave of the coronavirus disease 2019 pandemic) and 695 (second wave of the coronavirus disease 2019 pandemic) coronavirus disease 2019 patients admitted to the hospital, with median age first wave of the coronavirus disease 2019 pandemic as 68 (57–80) and second wave of the coronavirus disease 2019 pandemic as 71 (60–80) (p = 0.15), and similar admission severity. For the first wave of the coronavirus disease 2019 pandemic versus second wave of the coronavirus disease 2019 pandemic, 30-day mortality was 74/341 (22%) and 98/662 (15%) (p = 0.007). In the ward, 11/341 (3.2%) and 404/662 (61%) received dexamethasone (p < 0.001); 6/341 (2%) and 79/662 (12%) received high-flow nasal oxygen (p < 0.0001); 2/341 (0.6%) and 88/662 (13.3%) received remdesivir (p < 0.0001); 249/341 (73%) and 0/662 (0%) received hydroxychloroquine (p < 0.0001); and 87/341 (26%) and 128/662 (19%) (p = 0.024) patients were transferred to ICU. On ICU admission, median Sequential Organ Failure Assessment was 6 (3–7) and 4 (3–6) (p = 0.02). High-flow nasal oxygen was given to 16/87 (18%) and 102/128 (80%) (p < 0.001); 69/87 (79%) and 56/128 (44%) received mechanical ventilation (p < 0.001) with durations 17 days (10–26 d) and 10 days (5–17 d) (p = 0.01). Median ICU length of stay was 14 days (5–27 d) and 6 days (3–11 d) (p < 0.001). Finally, 16/87 (18%) and 8/128 (6%) received renal replacement therapy (p = 0.0055); and 64/87 (74%) and 51/128 (40%) needed vasopressor support (p < 0.001). Conclusions: The main therapeutic changes between the first wave of the coronavirus disease 2019 pandemic and the second wave of the coronavirus disease 2019 pandemic were use of steroids, unrestrictive use of high-flow nasal oxygen for hypoxemic patients, and transfer of patients to other geographic areas in the case of ICU overcrowding. These changes were associated with a decrease in 30-day mortality, ICU admission, and organ support.

Supplemental Digital Content is available in the text., Objectives: There has been controversy about the timing and indications for intubation and mechanical ventilation in novel coronavirus disease 2019. This study assessed the effect of early intubation and mechanical ventilation on all-cause, inhospital mortality for coronavirus disease 2019 patients. Design: Multicenter retrospective cohort study. Setting: Eleven municipal hospitals in New York City from March 1, 2020, to December 1, 2020. Patients: Adult patients who tested positive for coronavirus disease 2019 in the emergency department were subsequently admitted. Patients with do-not-intubate orders at admission were excluded. Interventions: Intubation within 48 hours of triage and intubation at any point during hospital stay. Measurements and Main Results: Data from 7,597 coronavirus disease 2019 patients were included; of these, 1,628 (21%) were intubated overall and 807 (11%) were intubated within 48 hours of triage. After controlling for available confounders, intubation rates for coronavirus disease 2019 patients varied significantly across hospitals and decreased steadily as the pandemic progressed. After nearest neighbor propensity score matching, intubation within 48 hours of triage was associated with higher all-cause mortality (hazard ratio, 1.30 [1.15–1.48]; p < 0.0001), as was intubation at any time point (hazard ratio, 1.62 [1.45–1.80]; p < 0.0001). Among intubated patients, intubation within 48 hours of triage was not significantly associated with differences in mortality (hazard ratio, 1.09 [0.94–1.26]; p = 0.26). These results remained robust to multiple sensitivity analyses. CONCLUSIONS: Intubation within 48 hours of triage, as well as at any time point in the hospital course, was associated with increased mortality in coronavirus disease 2019 patients in this observational study.

Supplemental Digital Content is available in the text., OBJECTIVES: To characterize prearrest hemodynamic trajectories of children suffering inhospital cardiac arrest. DESIGN: Exploratory retrospective analysis of arterial blood pressure and electrocardiogram waveforms. SETTING: PICU and cardiac critical care unit in a tertiary-care children’s hospital. PATIENTS: Twenty-seven children with invasive blood pressure monitoring who suffered a total of 31 inhospital cardiac arrest events between June 2017 and June 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed changes in cardiac output, systemic vascular resistance, stroke volume, and heart rate derived from arterial blood pressure waveforms using three previously described estimation methods. We observed substantial prearrest drops in cardiac output (population median declines of 65–84% depending on estimation method) in all patients in the 10 minutes preceding inhospital cardiac arrest. Most patients’ mean arterial blood pressure also decreased, but this was not universal. We identified three hemodynamic patterns preceding inhospital cardiac arrest: subacute pulseless arrest (n = 18), acute pulseless arrest (n = 7), and bradycardic arrest (n = 6). Acute pulseless arrest events decompensated within seconds, whereas bradycardic and subacute pulseless arrest events deteriorated over several minutes. In the subacute and acute pulseless arrest groups, decreases in cardiac output were primarily due to declines in stroke volume, whereas in the bradycardic group, the decreases were primarily due to declines in heart rate. CONCLUSIONS: Critically ill children exhibit distinct physiologic behaviors prior to inhospital cardiac arrest. All events showed substantial declines in cardiac output shortly before inhospital cardiac arrest. We describe three distinct prearrest patterns with varying rates of decline and varying contributions of heart rate and stroke volume changes to the fall in cardiac output. Our findings suggest that monitoring changes in arterial blood pressure waveform-derived heart rate, pulse pressure, cardiac output, and systemic vascular resistance estimates could improve early detection of inhospital cardiac arrest by up to several minutes. Further study is necessary to verify the patterns witnessed in our cohort as a step toward patient rather than provider-centered definitions of inhospital cardiac arrest.

Supplemental Digital Content is available in the text., OBJECTIVES: With percutaneous left ventricular mechanical circulatory support devices becoming increasingly available for patients with cardiogenic shock due to acute myocardial infarction and the lack of a clear mortality benefit to date, identifying optimal candidates for this technology is crucial. We studied the effectiveness of Impella Cardiac Pow (Abiomed, Danvers, MA) in various stages of cardiogenic shock and elderly cohorts. DESIGN: Retrospective review. SETTING: Data were collected for patients at a single community hospital between January 1, 2018, and December 31, 2019. SUBJECTS: Thirty-one consecutive adult patients with cardiogenic shock due to acute myocardial infarction who received Impella Cardiac Pow support. Shock stages were defined by the Society for Cardiovascular Angiography and Intervention (Stages A–E). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was in-hospital death across Society for Cardiovascular Angiography and Intervention cardiogenic shock stages and in patients greater than or equal to 80 and less than 80 years old. Secondary outcomes were Valve Academic Research Consortium-2 vascular and bleeding complications, stroke, and renal failure requiring dialysis. The median age of the study population was 64 years, with seven patients (23%) being greater than or equal to 80 years old. No patients were in Society for Cardiovascular Angiography and Intervention Stage A, whereas there were seven in B, eight in C, six in D, and 10 (32%) in E. Overall in-hospital mortality occurred in 61% of patients. All 10 patients in Stage E died before hospital discharge. Mortality occurred in 54% of patients (13/24) age less than 80 years compared with 86% of those 80 years or older (6/7). A total of 38.7% of patients (12/31) and 32.3% of patients (10/31) experienced Valve Academic Research Consortium-2 bleeding and vascular events, which were evenly distributed across Society for Cardiovascular Angiography and Intervention cardiogenic shock Stages. CONCLUSIONS: In conclusion, patients with shock in extremis and those 80 years old and older may have a prohibitively high mortality despite Impella use. These findings merit further prospective investigation in a larger number of patients to evaluate the effectiveness of Impella (and other left ventricular mechanical circulatory devices) and the inherent resource utilization in advanced cardiogenic shock and the elderly.

Supplemental Digital Content is available in the text., OBJECTIVES: To evaluate whether different approaches in note text preparation (known as preprocessing) can impact machine learning model performance in the case of mortality prediction ICU. DESIGN: Clinical note text was used to build machine learning models for adults admitted to the ICU. Preprocessing strategies studied were none (raw text), cleaning text, stemming, term frequency-inverse document frequency vectorization, and creation of n-grams. Model performance was assessed by the area under the receiver operating characteristic curve. Models were trained and internally validated on University of California San Francisco data using 10-fold cross validation. These models were then externally validated on Beth Israel Deaconess Medical Center data. SETTING: ICUs at University of California San Francisco and Beth Israel Deaconess Medical Center. SUBJECTS: Ten thousand patients in the University of California San Francisco training and internal testing dataset and 27,058 patients in the external validation dataset, Beth Israel Deaconess Medical Center. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mortality rate at Beth Israel Deaconess Medical Center and University of California San Francisco was 10.9% and 7.4%, respectively. Data are presented as area under the receiver operating characteristic curve (95% CI) for models validated at University of California San Francisco and area under the receiver operating characteristic curve for models validated at Beth Israel Deaconess Medical Center. Models built and trained on University of California San Francisco data for the prediction of inhospital mortality improved from the raw note text model (AUROC, 0.84; CI, 0.80–0.89) to the term frequency-inverse document frequency model (AUROC, 0.89; CI, 0.85–0.94). When applying the models developed at University of California San Francisco to Beth Israel Deaconess Medical Center data, there was a similar increase in model performance from raw note text (area under the receiver operating characteristic curve at Beth Israel Deaconess Medical Center: 0.72) to the term frequency-inverse document frequency model (area under the receiver operating characteristic curve at Beth Israel Deaconess Medical Center: 0.83). CONCLUSIONS: Differences in preprocessing strategies for note text impacted model discrimination. Completing a preprocessing pathway including cleaning, stemming, and term frequency-inverse document frequency vectorization resulted in the preprocessing strategy with the greatest improvement in model performance. Further study is needed, with particular emphasis on how to manage author implicit bias present in note text, before natural language processing algorithms are implemented in the clinical setting.

Supplemental Digital Content is available in the text., OBJECTIVES: Hyperoxia is common among critically ill patients and may increase morbidity and mortality. However, limited evidence exists for critically injured patients. The objective of this study was to determine the association between hyperoxia and in-hospital mortality in adult trauma patients requiring ICU admission. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, retrospective cohort study was conducted at two level I trauma centers and one level II trauma center in CO between October 2015 and June 2018. All adult trauma patients requiring ICU admission within 24 hours of emergency department arrival were eligible. The primary exposure was oxygenation during the first 7 days of hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was in-hospital mortality. Secondary outcomes were hospital-free days and ventilator-free days. We included 3,464 critically injured patients with a mean age of 52.6 years. Sixty-five percent were male, and 66% had blunt trauma mechanism of injury. The primary outcome of in-hospital mortality occurred in 264 patients (7.6%). Of 226,057 patient-hours, 46% were spent in hyperoxia (oxygen saturation > 96%) and 52% in normoxia (oxygen saturation 90–96%). During periods of hyperoxia, the adjusted risk for mortality was higher with greater oxygen administration. At oxygen saturation of 100%, the adjusted risk scores for mortality (95% CI) at Fio2 of 100%, 80%, 60%, and 50% were 6.4 (3.5–11.8), 5.4 (3.4–8.6), 2.7 (1.7–4.1), and 1.5 (1.1–2.2), respectively. At oxygen saturation of 98%, the adjusted risk scores for mortality (95% CI) at Fio2 of 100%, 80%, 60%, and 50% were 7.7 (4.3–13.5), 6.3 (4.1–9.7), 3.2 (2.2–4.8), and 1.9 (1.4–2.7), respectively. CONCLUSIONS: During hyperoxia, higher oxygen administration was independently associated with a greater risk of mortality among critically injured patients. Level of evidence: Cohort study, level III.

Supplemental Digital Content is available in the text., Objectives: Treatment of hypoxemic respiratory failure and acute respiratory distress syndrome is complex. Evidence-based therapies that can improve survival and guidelines advocating their use exist; however, implementation is inconsistent. Our objective was to develop and validate an evidence-based, stakeholder-informed standardized management pathway for hypoxemic respiratory failure and acute respiratory distress syndrome to improve adherence to best practice. Design: A standardized management pathway was developed using a modified Delphi consensus process with a multidisciplinary group of ICU clinicians. The proposed pathway was externally validated with a survey involving multidisciplinary stakeholders and clinicians. Setting: In-person meeting and web-based surveys of ICU clinicians from 17 adult ICUs in the province of Alberta, Canada. Intervention: Not applicable. Measurements and Main Results: The consensus panel was comprised of 30 ICU clinicians (4 nurses, 10 respiratory therapists, 15 intensivists, 1 nurse practitioner; median years of practice 17 [interquartile range, 13–21]). Ninety-one components were serially rated and revised over two rounds of online and one in-person review. The final pathway included 46 elements. For the validation survey, 692 responses (including 59% nurses, 33% respiratory therapists, 7% intensivists and 1% nurse practitioners) were received. Agreement of greater than 75% was achieved on 43 of 46 pathway elements. Conclusions: A 46-element evidence-informed hypoxemic respiratory failure and acute respiratory distress syndrome standardized management pathway was developed and demonstrated to have content validity.

Supplemental Digital Content is available in the text., Objectives: ICU treatments frequently result in long-term psychologic impairments, negatively affecting quality of life. An effective treatment strategy is still lacking. The aim of this study was to describe and evaluate the safety and immersiveness of a newly designed ICU-specific virtual reality module. Design: A randomized controlled healthy volunteer trial. Setting: ICU of the Franciscus Gasthuis & Vlietland Hospital (Rotterdam, the Netherlands), a large teaching hospital. Participants: Forty-five virtual reality–naive healthy volunteers. Interventions: Volunteers were randomized to three arms: the head-mounted display virtual reality group (n = 15), the 2D group (n = 15), and the crossover group (n = 15). Safety was assessed by changes in vital signs and the occurrence of simulator sickness (Simulator Sickness Questionnaire). Immersiveness was assessed using the Igroup Presence Questionnaire. Measurements and Main Results: Volunteers in the head-mounted display virtual reality group experienced more mild symptoms of simulator sickness, expressed as symptoms of dizziness (p = 0.04) and stomach awareness (p = 0.04), than the 2D group. Nevertheless, none of the individual Simulator Sickness Questionnaire items were scored as being severe, no changes in vital signs were observed, and no sessions were prematurely stopped. Volunteers in the crossover group experienced a higher total presence (p < 0.001) when using head-mounted display virtual reality, expressed as a higher sense of presence (p < 0.001), more involvement (p < 0.01), and more experienced realism (p < 0.001). Conclusions: ICU-specific virtual reality appears safe and more immersive than 2D, implicating that ICU-specific virtual reality is feasible for clinical use. One should however be aware of simulator sickness-related symptoms. Future research is needed to confirm these findings in survivors of critical illness.

Supplemental Digital Content is available in the text., OBJECTIVES: To investigate patients’ experience of ICU diaries 6 months after ICU discharge among survivors. This study was designed to add insight into a large randomized study, which found no benefit of the ICU diary to post-traumatic stress disorder among critically ill patients having received mechanical ventilation. DESIGN: A preplanned qualitative substudy of patients receiving an ICU diary written by ICU caregivers and families. Six months after ICU discharge, survivors were contacted by a psychologist for a telephone interview using a semi-directive guide. SETTING: Thirty-five French ICUs. PATIENTS: All ICU survivors having received an ICU diary. INTERVENTION: An ICU diary written by both ICU staff and families. MEASUREMENTS AND MAIN RESULTS: Among the 332 patients randomized in the intervention group (having had an ICU diary filled by both ICU staff and families), 191 (57.7%) were alive at 6 months and 101 of 191 (52.9%) participated in a telephone interview. They were (median [interquartile range]) 64 years old (53–70 yr old); 65 (64.4%) were men, and 79 (78.2%) were medical patients. Duration of ICU stay was 13 days (8–21 d). Three themes were derived from the thematic analysis: 1) reading the diary: between emotion and pain, 2) how the diary helped, and 3) the bittersweet representation of the diary. For half of the patients, the diary is a good memory of difficult times (55/101, 54.5%), others seem to be more ambivalent about it (28/101, 27.8%), and 37 of 101, 36.6% see it as a painful representation of a time to be forgotten. CONCLUSIONS: When reading their ICU diaries, ICU survivors experienced mixed emotions, related to family messages, medical caregiving, and to the severity of their illness. Patients described diaries as a help or a hindrance to recovery, depending on their wish to remember the period or move on from it.

Supplemental Digital Content is available in the text., OBJECTIVES: The purpose of this study is to evaluate the overall occurrence of inhospital mortality in trauma patients who were placed on extracorporeal membrane oxygenation following the complication of the acute respiratory distress syndrome. DESIGN: Observational cohort study. SETTING: The data of all patients who were traumatically injured and developed the complication of acute respiratory distress syndrome were accessed from the Trauma Quality Improvement Program database from the calendar years of 2013 to 2016. PATIENTS: Patients 16 years old and less than 90 years old were included in the study. Variables included patient demography, Injury Severity Score, Glasgow Coma Scale score, Abbreviated Injury Scale score, and outcomes. INTERVENTIONS: Extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Propensity-matched analysis was performed between two groups: patients placed on extracorporeal membrane oxygenation and patients placed on conventional mode of ventilation. The primary outcome was inhospital mortality. Out of 6,121 patients who developed acute respiratory distress syndrome, 118 patients (1.93%) were placed on extracorporeal membrane oxygenation. The pair matched analysis showed significant difference between the two groups (extracorporeal membrane oxygenation vs conventional mode of ventilation) for overall inhospital mortality (35.6% vs 14.4%; p < 0.001). There were significant differences found between the two groups for the median hospital length of stay (41 [35–49] vs 27 [24–33]), ICU days (35 [30–41] vs 19 [17–24]), and ventilator days (30 [27–34] vs 15 [13–18]). All p values are less than 0.001. CONCLUSIONS: Approximately 2% of acute respiratory distress syndrome patients were placed on extracorporeal membrane oxygenation. The overall inhospital mortality remained high despite patients being placed on extracorporeal membrane oxygenation.

Supplemental Digital Content is available in the text., Objectives: The plasma level of N-terminal pro-brain natriuretic peptide is regulated by sex hormones. It has been controversial whether N-terminal pro-brain natriuretic peptide is a prognosis marker for sepsis. The aim of this study is to examine the sex-dependent association of plasma N-terminal pro-brain natriuretic peptide with organ dysfunction and mortality of sepsis patients. Design: In this retrospective study, the association between plasma N-terminal pro-brain natriuretic peptide concentration on the day of sepsis diagnosis and the degree of organ dysfunction, occurrence of septic shock, or 30-day mortality in both male and female patients was analyzed. Setting: This study was conducted in the Sepsis Laboratory at the Huaihe Hospital of Henan University in China. Patients: Diagnoses of sepsis, and septic shock, were based on the recently revised criteria (Sepsis 3.0). All sepsis patients (517) hospitalized in the respiratory ICU of the Huaihe Hospital from June 2016 to December 2019 were enrolled in this study. Interventions: None. Measurements and Main Results: No significant difference was found in the age, occurrence rate of septic shock, 30-day mortality, or degree of organ dysfunction between male and female patients. Median concentration of plasma N-terminal pro-brain Natriuretic peptide was higher by 93.48% in female than male patients. A significant association was found between N-terminal pro-brain natriuretic peptide and septic shock or 30-day mortality in female, but not in male patients of community- or hospital-acquired sepsis. N-terminal pro-brain natriuretic peptide levels correlated to functional deficiencies of the cardiac and nervous systems, only in female patients. Conclusions: The plasma N-terminal pro-brain natriuretic peptide level is a female-specific prognosis indicator of septic shock and mortality.

Supplemental Digital Content is available in the text., Objectives: To use latent class growth analysis to identify posttraumatic stress disorder symptom trajectories in ICU family caregivers. Design: Prospective cohort study. Setting: The medical ICU at a tertiary-care center in the United States. Participants: Adult patients experiencing acute cardiorespiratory failure (defined as requiring at least one of the following: 1) vasopressors, 2) noninvasive positive pressure ventilation, 3) high-flow nasal cannula, or 4) mechanical ventilation) were enrolled in a pair with their primary family caregivers. Measurements and Main Results: Participants were enrolled within the first 48 hours of ICU admission. Family caregiver posttraumatic stress disorder symptoms were measured using the Impact of Events Scale-Revised at four time points: at enrollment, shortly after ICU discharge, and at 3 and 6 months after ICU discharge. The data were examined using latent class growth analysis to identify posttraumatic stress disorder symptom trajectories. Two distinct symptom trajectories were identified: a persistently high trajectory, characterized by high posttraumatic stress disorder symptoms at initial assessment, which remained elevated over time, and a persistently low trajectory, characterized by low posttraumatic stress disorder symptoms at initial assessment, which remained low over time. Approximately two-thirds of caregivers belonged to the persistently high trajectory, and one-third of caregivers belonged to the persistently low trajectory. Conclusions: Using latent class growth analysis to measure 6-month ICU family caregiver posttraumatic stress disorder symptom trajectories, we identified two distinct trajectories (persistently low and persistently high). A larger cohort study is warranted to further delineate posttraumatic stress disorder trajectories in this population, with the ultimate goal of targeting high-risk caregivers for interventions to reduce psychologic distress and improve long-term caregiver outcomes.

Objectives:. To assess differences in cognitive outcomes and sleep in adult survivors of critical illness, managed with venovenous extracorporeal membrane oxygenation as compared to conventional mechanical ventilation only. Design:. Retrospective cohort study linked with data from the COGnitive outcomes and WELLness study. Setting:. A multisite study from five adult medical/surgical ICUs in Toronto. Patients:. Thirty-three ICU survivors including adult patients who received venovenous extracorporeal membrane oxygenation (n = 11) matched with patients who received mechanical ventilation only (n = 22) using specified covariates (e.g., age). Interventions:. None. Measurements and Main Results:. Baseline demographics and admission diagnoses were collected at enrollment. Cognitive outcome was evaluated using the Repeatable Battery for the Assessment of Neuropsychologic Status (global cognitive function) and Trail Making Test B (executive function), and sleep variables were estimated using actigraphy. Assessments occurred at 7 days post ICU discharge and again at 6- and 12-month follow-up. No statistically significant difference was seen between patients treated with or without venovenous extracorporeal membrane oxygenation in the mean daily Riker Sedation Agitation Score; however, patients in the venovenous extracorporeal membrane oxygenation group received greater amounts of fentanyl over their ICU stay as compared to patients receiving conventional mechanical ventilation only (p < 0.001). No significant differences were found in performance on either of the cognitive assessment tools, between survivors treated or not with venovenous extracorporeal membrane oxygenation at any of the time points assessed. Total sleep time estimated by actigraphy increased from approximately 6.5 hours in hospital to 7.5 hours at 6-month follow-up in all patients, regardless of treatment type. Total sleep time remained consistent in both groups from 6 to 12 months post ICU discharge. Conclusions:. In this small retrospective case series, no significant differences were found in sleep or cognitive outcomes between extracorporeal life support and non–extracorporeal life support survivors. Further, in this hypothesis-generating study, differences in administered sedative doses during the ICU stay seen between the two groups did not impact 6- or 12-month cognitive performance or actigraphy-estimated sleep time.

Objectives:. To identify the most efficacious timing for tocilizumab administration in critically ill patients infected with severe acute respiratory syndrome coronavirus-2. Design:. Observational multicenter cohort study. Setting:. A total of 23 acute care hospitals in four states. Patients:. One-hundred eighteen patients admitted between March 13, 2020, and April 16, 2020. Eighty-one patients received tocilizumab, and 37 were untreated and served as a control group. Measurements and Main Results:. The main outcome was mortality and was analyzed by timing of tocilizumab dosing. Early dosing was defined as a tocilizumab dose administered prior to or within 1 day of intubation. Late dosing was defined as a dose administered greater than 1 day after intubation. A control group that was treated only with standard of care, and without tocilizumab, was used for comparison. Early tocilizumab therapy was associated with a statistically significant decrease in mortality as compared to patients who were untreated (p = 0.003). Dosing tocilizumab late was associated with an increased mortality compared with the untreated group (p = 0.006). Conclusions:. Early tocilizumab administration was associated with decreased mortality in critically ill severe acute respiratory syndrome coronavirus-2 patients, but a potential detriment was suggested by dosing later in a patient’s course.

Objectives:. To determine how several existing crisis standards of care triage protocols would have distinguished between patients with coronavirus disease 2019 requiring intensive care. Design:. Retrospective cohort study. Setting:. Single urban academic medical center. Patients:. One-hundred twenty patients with coronavirus disease 2019 who required intensive care and mechanical ventilation. Interventions:. None. Measurements and Main Results:. The characteristics of each patient at the time of ICU triage were used to determine how patients would have been prioritized using four crisis standards of care protocols. The vast majority of patients in the cohort would have been in the highest priority group using a triage protocol focusing on Sequential Organ Failure Assessment alone. Prioritization based on Sequential Organ Failure Assessment and 1-year life expectancy would have resulted in only slightly more differentiation between patients. Prioritization based on Sequential Organ Failure Assessment and 5-year life expectancy would have added significant additional differentiation depending on how priority groups were defined. Conclusions:. There is considerable controversy regarding the use of criteria other than prognosis for short-term survival in initial allocation of critical care resources under crisis standards of care triage protocols. To the extent that initial triage protocols would not create sufficient differentiation between patients, effectively resulting in a first-come, first-served initial allocation of resources, it is important to focus on how resources would be reallocated in the event of ongoing scarcity.

Objectives:. Critical care teams are encouraged to follow best practice protocols to help wean mechanically ventilated patients from the ventilator to reduce ventilator-associated events including ventilator-associated conditions, probable ventilator-associated pneumonias, and infection-related ventilator-associated conditions. Providers monitor for alerts suggestive of possible ventilator-associated events and advise when patients should undergo spontaneous breathing trials. Compliance with protocols in most units is suboptimal. Design:. Retrospective review of clinical data over 24 months. Setting:. St. Joseph Mercy Hospital Candler Hospital Medical-Surgical ICU. Patients:. All mechanically ventilated patients. Interventions:. The Respiratory Knowledge Portal was implemented in our ICU. For 13 months, Respiratory Knowledge Portal data were ported to ICU workstations (control). For the following 11 months, Respiratory Knowledge Portal data were also presented on tablet computers (intervention) for use during multidisciplinary rounds. We performed a retrospective review of Respiratory Knowledge Portal data from before and after the implementation of the tablet computers. Measurements and Main Results:. Data were collected from 337 patients (187 control group, 150 intervention group). A decrease in the occurrence of ventilator-associated events was observed during the intervention group compared with the control group. Only 2.0% of patients in the intervention group experienced any category of ventilator-associated event, while 11.2% of patients in the control group experienced one event (p = 0.003). Intervention patients experienced less ventilator-associated conditions (p = 0.002), infection-related ventilator-associated conditions (p = 0.026), and probable ventilator-associated pneumonias (p = 0.036) than control patients. Twenty-one of the 24 patients with any ventilator-associated events were in the control group. There was no significant difference between the days spent on ventilation nor hospital length of stay in the control compared with intervention group patients. Conclusions:. Fewer ventilator-associated events, ventilator-associated conditions, infection-related ventilator-associated conditions, and probable ventilator-associated pneumonias were seen during the period when Respiratory Knowledge Portal monitoring data was presented on tablet computers. There was no difference in time on ventilator nor overall length of stay.

Supplemental Digital Content is available in the text., Objectives: To comprehensively classify interventions performed by emergency medicine clinical pharmacists and quantify cost avoidance generated through their accepted interventions. Design: A multicenter, prospective, observational study was performed between August 2018 and January 2019. Setting: Community and academic hospitals in the United States. Participants: Emergency medicine clinical pharmacists. Interventions: Recommendations classified into one of 38 intervention categories associated with cost avoidance. Measurements and Main Results: Eighty-eight emergency medicine pharmacists at 49 centers performed 13,984 interventions during 917 shifts that were accepted on 8,602 patients and generated $7,531,862 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established categories were as follows: adverse drug event prevention (1,631 interventions; $2,225,049 cost avoidance), resource utilization (628; $310,582), individualization of patient care (6,122; $1,787,170), prophylaxis (24; $22,804), hands-on care (3,533; $2,836,811), and administrative/supportive tasks (2,046; $342,881). Mean cost avoidance was $538.61 per intervention, $875.60 per patient, and $8,213.59 per emergency medicine pharmacist shift. The annualized cost avoidance from an emergency medicine pharmacist was $1,971,262. The monetary cost avoidance to pharmacist salary ratio was between $1.4:1 and $10.6:1. Conclusions: Pharmacist involvement in the care of patients presenting to the emergency department results in significant avoidance of healthcare costs, particularly in the areas of hands-on care and adverse drug event prevention. The potential monetary benefit-to-cost ratio for emergency medicine pharmacists is between $1.4:1 and $10.6:1.

Objectives:. To investigate the differences in clinical course, ventilator mechanics, and outcomes of patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection compared with a historical cohort of acute respiratory distress syndrome. Design:. Comparative case-control study. Setting:. Multicenter, comprehensive tertiary healthcare facility in Detroit, MI. Patients/Subjects:. Adult patients hospitalized with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection were compared with patients hospitalized with acute respiratory distress syndrome prior to the coronavirus disease 2019 pandemic (control). Interventions:. None. MEASUREMENTS AND Main Results:. We included 384 patients in the analysis. Inpatient mortality was significantly higher in patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection compared with controls (64% vs 49%; p = 0.007). Despite both groups demonstrating similar ventilatory function and Sequential Organ Failure Assessment score on day 1 of intubation, with similar lung compliance throughout the study period, patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection demonstrated progressive hypoxia compared with controls across the study period. Similarly, higher positive end-expiratory pressure levels and increased use of paralytics were observed in the patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection group. On univariate analysis of the entire cohort, significant risk factors for inpatient mortality included coronavirus disease 2019 infection (p = 0.007), older age (p < 0.001), high Sequential Organ Failure Assessment score (p = 0.003), vasopressor use (p = 0.039), paralytic use (p < 0.001), higher positive end-expiratory pressure levels on day 3 (p = 0.027) and day 7 (p < 0.001), in addition to acute respiratory distress syndrome severity on both days 3 (p = 0.008) and 7 (p < 0.001). Multivariate analysis identified coronavirus disease 2019 infection (odds ratio, 1.939; p = 0.021), older age (odds ratio, 1.042; p < 0.001), paralytic use (odds ratio, 3.366; p < 0.001), and higher Sequential Organ Failure Assessment score (odds ratio, 1.152; p = 0.027) as significant predictors of mortality across the entire cohort. Conclusions:. Patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection demonstrated higher mortality compared with control patients hospitalized with acute respiratory distress syndrome prior to the pandemic, with progressive hypoxia throughout the study period, despite similar lung mechanics and initial Sequential Organ Failure Assessment score. Coronavirus disease 2019 infection, older age, paralytic use, and higher Sequential Organ Failure Assessment scores were independent risk factors for 28-day mortality across the entire cohort.

Objectives:. Coronavirus disease 2019 continues to spread worldwide with high levels of morbidity and mortality. We performed anticoronavirus immunoglobulin G profiling of critically ill coronavirus disease 2019 patients to better define their underlying humoral response. Design:. Blood was collected at predetermined ICU days to measure immunoglobulin G with a research multiplex assay against four severe acute respiratory syndrome coronavirus 2 proteins/subunits and against all six additionally known human coronaviruses. Setting:. Tertiary care ICU and academic laboratory. Subjects:. ICU patients suspected of being infected with severe acute respiratory syndrome coronavirus 2 had blood collected until either polymerase chain reaction testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative) or until death or discharge if the patient tested polymerase chain reaction positive (coronavirus disease 2019 positive). Interventions:. None MEASUREMENTS AND MAIN RESULTS:. Age- and sex-matched healthy controls and ICU patients who were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients had greater body mass indexes, presented with bilateral pneumonias more frequently, and suffered lower Pao2:Fio2 ratios, when compared with coronavirus disease 2019 negative patients (p < 0.05). Mortality rate for coronavirus disease 2019 positive patients was 50%. On ICU days 1–3, anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G was significantly elevated in coronavirus disease 2019 positive patients, as compared to both healthy control subjects and coronavirus disease 2019 negative patients (p < 0.001). Weak severe acute respiratory syndrome coronavirus immunoglobulin G serologic responses were also detected, but not other coronavirus subtypes. The four anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G were maximal by ICU day 3, with all four anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G providing excellent diagnostic potential (severe acute respiratory syndrome coronavirus 2 Spike 1 protein immunoglobulin G, area under the curve 1.0, p < 0.0005; severe acute respiratory syndrome coronavirus receptor binding domain immunoglobulin G, area under the curve, 0.93–1.0; p ≤ 0.0001; severe acute respiratory syndrome coronavirus 2 Spike proteins immunoglobulin G, area under the curve, 1.0; p < 0.0001; severe acute respiratory syndrome coronavirus 2 Nucleocapsid protein immunoglobulin G area under the curve, 0.90–0.95; p ≤ 0.0003). Anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G increased and/or plateaued over 10 ICU days. Conclusions:. Critically ill coronavirus disease 2019 patients exhibited anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G, whereas serologic responses to non–severe acute respiratory syndrome coronavirus 2 antigens were weak or absent. Detection of human coronavirus immunoglobulin G against the different immunogenic structural proteins/subunits with multiplex assays may be useful for pathogen identification, patient cohorting, and guiding convalescent plasma therapy.

Supplemental Digital Content is available in the text., Objectives: To explain and demonstrate a new approach for rapidly developing a decision-support tool for prioritizing patients with coronovirus 2019 disease for admission to ICUs. Design: An expert group used multi-criteria decision analysis methods to specify criteria and weights, representing their relative importance, for prioritizing patients with coronovirus 2019 disease with respect to likely clinical benefit. Specialized multi-criteria decision analysis software, implementing the “Potentially All Pairwise RanKings of all possible Alternatives” method to determine the weights, was used. Social equity considerations for prioritizing patients were also identified as important. Setting: The prioritization tool was developed in New Zealand. Subjects: An expert group comprising specialists from intensive care medicine and nursing, Māori (New Zealand’s indigenous population) health, infectious diseases, and neonatology was formed. The group’s work was supported by health economists and decision analysts and overseen by an ethicist and a senior representative from the New Zealand Ministry of Health. Interventions: Multi-criteria decision analysis to create a prioritization tool. Measurements and Main Results: The prioritization tool comprised eight criteria with respect to likely clinical benefit. In decreasing order of importance (weights in parentheses): Sequential Organ Failure Assessment score (15.7%), preexisting cardiovascular conditions (15.7%), functional capacity (15.7%), age (12.4%), preexisting respiratory conditions (11.1%), immunocompromised (11.1%), body mass index (9.2%), and other relevant medical conditions (9.2%). Two social equity considerations were also included in the overarching decision framework to be used alongside the clinical criteria: prioritizing Māori and Pacific people (and, potentially, other at-risk groups), and healthcare and other frontline workers. Conclusions: The criteria and weights in the prioritization tool can be easily revised as new evidence emerges. The approach for developing the tool could be used in other countries whose ICUs are at risk of being overwhelmed by the coronavirus disease 2019 pandemic to rapidly develop their own prioritization tools. In the event that future crises threaten to overload ICUs, other prioritization tools could also be rapidly developed.

Objectives:. Researchers have shown in laboratory studies that different types of fabrics were associated with changes in skin moisture, friction, shear, and temperature that may predispose patients to pressure injury. There was an association between type of fiber used in hospital linens and pressure injury development in previous clinical studies. We examined if bed linens made from a newly developed synthetic fiber fabric affected occurrence rate, time to development, and severity of unit-acquired pressure injury in critically ill adult inpatients. Design:. Cluster randomized controlled trial. Setting:. Five adult medical ICUs within one quaternary care center in the Midwest United States. Patients:. Patients were assigned to a unit based on bed availability. In total, there were 3,332 patients in the study. INTERVENTIONS:. Participating medical ICUs were randomly assigned to cotton fiber or synthetic fiber linens for the first 6 months of the study period, and assignment reversed after a 14-day washout period for the final 6 months. Measurements and Main Results:. Unit-acquired pressure injury occurrence rate, time to first unit-acquired pressure injury, and severity were evaluated using generalized mixed effect models with patient as a random effect, and a marginal Cox proportional hazards model with repeated admissions from the same patient accounted for by use of a sandwich estimator of the variance. There were 1,706 patients on cotton fiber linens and 1,626 patients on synthetic fiber linens. Groups were similar on demographics except race and admitting diagnosis groupings. Occurrence rate (p = 0.99), time to development (p = 0.99), and maximum severity of unit-acquired pressure (p = 0.86) were similar between groups before and after controlling for race and admitting diagnosis groupings. Conclusions:. Linen type did not affect unit-acquired pressure injury occurrence rate, severity, or timing. Standard unit-acquired pressure injury prevention efforts may be more cost-effective than investment in synthetic fiber linens.

Objectives:. Given finite ICU bed capacity, knowledge of ICU bed utilization during the coronavirus disease 2019 pandemic is critical to ensure future strategies for resource allocation and utilization. We sought to examine ICU census trends in relation to ICU bed capacity during the rapid increase in severe coronavirus disease 2019 cases early during the pandemic. Design:. Observational cohort study. Setting:. Thirteen geographically dispersed academic medical centers in the United States. Patients/Subjects:. We obtained daily ICU censuses from March 26 to June 30, 2020, as well as prepandemic ICU bed capacities. The primary outcome was daily census of ICU patients stratified by coronavirus disease 2019 and mechanical ventilation status in relation to ICU capacity. Interventions:. None. Measurements and Main Results:. Prepandemic overall ICU capacity ranged from 62 to 225 beds (median 109). During the study period, the median daily coronavirus disease 2019 ICU census per hospital ranged from 1 to 84 patients, and the daily ICU census exceeded overall ICU capacity for at least 1 day at five institutions. The number of critically ill patients exceeded ICU capacity for a median (interquartile range) of 17 (12–50) of 97 days at these five sites. All 13 institutions experienced decreases in their noncoronavirus disease ICU population, whereas local coronavirus disease 2019 cases increased. Coronavirus disease 2019 patients reached their greatest proportion of ICU capacity on April 12, 2020, when they accounted for 44% of ICU patients across all participating hospitals. Maximum ICU census ranged from 52% to 289% of overall ICU capacity, with three sites less than 80%, four sites 80–100%, five sites 100–128%, and one site 289%. Conclusions:. From March to June 2020, the coronavirus disease 2019 pandemic led to ICU censuses greater than ICU bed capacity at fives of 13 institutions evaluated. These findings demonstrate the short-term adaptability of U.S. healthcare institutions in redirecting limited resources to accommodate a public health emergency.

Objectives:. We aimed to describe the characteristics and outcome in children with severe Mycoplasma pneumoniae pneumonia in a Chinese PICU. Design:. A retrospective observational study from 2017 to 2019. Setting:. A 36-bed university tertiary PICU at Shanghai Children’s Hospital. Patients:. Patients admitted to a tertiary PICU 29 days to 18 years old screened for laboratory-confirmed severe M. pneumoniae pneumonia. Interventions:. None. Measurements and Main Results:. Descriptive analysis of baseline characteristics for patients included hospital mortality, organ dysfunctions, use of mechanical ventilation, continuous renal replacement therapy, and/or extracorporeal membrane oxygenation. A total of 817 children with severe pneumonia were admitted to PICU, and 203 of 817 cases (24.8%) with severe M. pneumoniae pneumonia were included in this study. The median age was 41 months (interquartile range, 20–67 mo), of which 77.3% (157/203) were younger than 6 years old. Among 163 patients with the test for macrolide resistance, 90.2% cases (147/163) were macrolide-resistant M. pneumoniae. Severe M. pneumoniae pneumonia-associated organ dysfunction included acute respiratory failure (203 cases, 100%), followed by cardiovascular disorder (79/203, 38.9%), gastrointestinal dysfunction (24/203, 11.8%). The main complications were pleural effusion (79/203, 38.9%), capillary leak syndrome (58/203, 28.6%), and plastic bronchitis (20/203, 9.9%). All patients needed respiratory support, including 64.5% patients (131/203) who received mechanical ventilation and 35.5% patients (72/203) who received high-flow nasal oxygen. Twenty-five patients (12.3%) treated with continuous renal replacement therapy and nine cases (4.4%) received extracorporeal membrane oxygenation. The case fatality rate was 3.9% (8/203). Furthermore, cardiovascular dysfunction, liver injury, or multiple organ dysfunction syndrome were associated with longer mechanical ventilation duration, delayed PICU discharge, and high hospital mortality. Coinfection was a risk factor of delayed PICU discharge. Conclusions:. Children with severe M. pneumoniae pneumonia mainly occur under the age of 6 years, showing a high proportion of extrapulmonary organ dysfunction and macrolide resistances. Extrapulmonary organ dysfunction and coinfection are associated with worse outcomes. The overall mortality is relatively low after treated with appreciate antibiotics, respiratory support, and extracorporeal life support.

Supplemental Digital Content is available in the text., Objectives: To investigate the change in rate of invasive procedures (endotracheal intubation, central venous catheters, arterial catheters, and peripheral inserted central venous catheters) performed in PICUs per admission over time. Secondarily, to investigate the change in type of respiratory support over time. Design: Retrospective study of prospectively collected data using the Virtual Pediatric Systems (VPS; LLC, Los Angeles, CA) database. Setting: North American PICUs. Patients: Patients admitted from January 2009 to December 2017. Interventions: None. Measurements and Main Results: There were 902,624 admissions from 161 PICUs included in the analysis. Since 2009, there has been a decrease in rate of endotracheal intubations, central venous catheters placed, and arterial catheters placed and an increase in the rate of peripheral inserted central venous catheter insertion per admission over time after controlling for severity of illness and unit level effects. As compared to 2009, the incident rate ratio for 2017 for endotracheal intubation was 0.90 (95% CI, 0.83–0.98; p = 0.017), for central venous line placement 0.69 (0.63–0.74; p < 0.001), for arterial catheter insertion 0.85 (0.79–0.92; p < 0.001), and for peripheral inserted central venous catheter placement 1.14 (1.03–1.26; p = 0.013). Over this time period, in a subgroup with available data, there was a decrease in the rate of invasive mechanical ventilation and an increase in the rate of noninvasive respiratory support (bilevel positive airway pressure/continuous positive airway pressure and high-flow nasal oxygen) per admission. Conclusions: Over 9 years across multiple North American PICUs, the rate of endotracheal intubations, central catheter, and arterial catheter insertions per admission has decreased. The use of invasive mechanical ventilation has decreased with an increase in noninvasive respiratory support. These data support efforts to improve exposure to invasive procedures in training and structured systems to evaluate continued competency.

Supplemental Digital Content is available in the text., Objectives: Changes in right ventricular size and function are frequently observed in patients with severe acute respiratory distress syndrome. The majority of patients who receive venovenous extracorporeal membrane oxygenation undergo chest CT and transthoracic echocardiography. The aims of this study were to compare the use of CT and transthoracic echocardiography to evaluate the right ventricular function and to determine the prevalence of acute cor pulmonale in this patient population. Design: Observational, retrospective, single-center, cohort study. Setting: Severe respiratory failure and extracorporeal membrane oxygenation center. Patients: About 107 patients with severe acute respiratory distress syndrome managed with venovenous extracorporeal membrane oxygenation. Interventions: Chest CT to evaluate right ventricular size and transthoracic echocardiography to evaluate right ventricular size and function. Measurements and Main Results: All 107 patients had a qualitative assessment of right ventricular size and function on transthoracic echocardiography. Quantitative measurements were available in 54 patients (50%) who underwent transthoracic echocardiography and in 107 of patients (100%) who received CT. Right ventricular dilatation was defined as a right ventricle end-diastolic diameter greater than left ventricular end-diastolic diameter upon visual assessment or an right ventricle end-diastolic diameter/left ventricular end-diastolic diameter and/or right ventricle cavity area/left ventricular cavity area of greater than 0.9. Right ventricle systolic function was visually estimated as being normal or impaired (visual right ventricular systolic impairment). The right ventricle was found to be dilated in 38/107 patients (36%) and in 58/107 patients (54%), using transthoracic echocardiography or CT right ventricle end-diastolic diameter/left ventricular end-diastolic diameter, respectively. When the CT right ventricle cavity/left ventricular cavity area criterion was used, the right ventricle was dilated in 19/107 patients (18%). About 33/107 patients (31%) exhibited visual right ventricular systolic impairment. Transthoracic echocardiography right ventricle end-diastolic diameter/left ventricular end-diastolic diameter showed good agreement with CT right ventricle cavity/left ventricular cavity area (R2 = 0.57; p < 0.01). A CT right ventricle cavity/left ventricular cavity area greater than 0.9 provided the optimal cutoff for acute cor pulmonale on transthoracic echocardiography with an AUC of 0.78. Acute cor pulmonale was defined by the presence of a right ventricle “D-shape” and quantitative right ventricle dilatation on transthoracic echocardiography or a right ventricle cavity/left ventricular cavity area greater than 0.9 on CT. A diagnosis of acute cor pulmonale was made in 9/54 (14% patients) on transthoracic echocardiography and in 19/107 (18%) on CT. Conclusions: Changes in right ventricular size and function are common in patients with severe acute respiratory distress syndrome requiring venovenous extracorporeal membrane oxygenation with up to 18% showing imaging evidence of acute cor pulmonale. A CT right ventricular cavity /left ventricular cavity area greater than 0.9 is indicative of impaired right ventricular systolic function.

Objectives:. To evaluate the effect of high-flow oxygen implementation on the respiratory rate as a first-line ventilation support in chronic obstructive pulmonary disease patients with acute hypercapnic respiratory failure. Design:. Multicenter, prospective, analytic observational case series study. Setting:. Five ICUs in Argentina, between August 2018 and September 2019. Patients:. Patients greater than or equal to 18 years old with moderate to very severe chronic obstructive pulmonary disease, who had been admitted to the ICU with a diagnosis of hypercapnic acute respiratory failure, were entered in the study. Interventions:. High-flow oxygen therapy through nasal cannula delivered using high-velocity nasal insufflation. Measurements and Main Results:. Forty patients were studied, 62.5% severe chronic obstructive pulmonary disease. After the first hour of high-flow nasal cannula implementation, there was a significant decrease of respiratory rate compared with baseline values, with a 27% decline (29 vs 21 breaths/min; p < 0.001). Furthermore, a significant reduction of Paco2 (57 vs 52 mm Hg [7.6 vs 6.9 kPa]; p < 0.001) was observed. The high-flow nasal cannula application failed in 18% patients. In this group, the respiratory rate, pH, and Paco2 showed no significant change during the first hour in these patients. Conclusions:. High-flow oxygen therapy through nasal cannula delivered using high-velocity nasal insufflation was an effective tool for reducing respiratory rate in these chronic obstructive pulmonary disease patients with acute hypercapnic respiratory failure. Early determination and subsequent monitoring of clinical and blood gas parameters may help predict the outcome.

Supplemental Digital Content is available in the text., Objectives: Practices regarding anticoagulation use in coronavirus disease 2019 focus primarily on its efficacy in the critically ill without a clear understanding of when to begin anticoagulation. We sought to understand the association of preinfection daily oral anticoagulation use and the short-term mortality of patients hospitalized with coronavirus disease 2019. Design: Retrospective chart review. Setting: Large health system with high coronavirus disease 2019 prevalence. Patients: Patients 60 years or older admitted to the hospital with positive coronavirus disease 2019 polymerase chain reaction test. Interventions: We compared both those on warfarin and those on a direct oral anticoagulant prior to admission and throughout disease course with those who were never exposed to an oral anticoagulant. Results: Our primary outcome was inhospital mortality at 21 days from the first coronavirus disease 2019 test ordered. Patients in the direct oral anticoagulant group (n = 104) were found to have significantly lower 21-day all-cause in hospital mortality than patients in the control group (n = 894) both prior to adjustment (14.4% vs 23.8%; odds ratio, 0.57 [0.29–0.92]; p = 0.03) and after controlling for age, gender, and comorbidities (odds ratio, 0.44 [0.20–0.90]; p = 0.033). Patients on warfarin (n = 28) were found to have an elevated unadjusted mortality rate of 32% versus 23.8% in the control group (odds ratio, 1.51 [0.64–3.31]; p = 0.31). After adjustment, a reduction in mortality was observed but not found to be statistically significant (odds ratio, 0.29 [0.02–1.62]; p = 0.24). There was no statistical difference noted in the number of bleeding events in each group. Conclusions: In this retrospective cohort study evaluating oral anticoagulant use among patients with coronavirus disease 2019, we found that patients who are on daily oral anticoagulation at the time of infection and throughout their disease course had significantly lower risk of all-cause mortality at 21 days. Validation of these findings should be performed on population-based levels. While research regarding anticoagulation algorithms is ongoing, we believe these results support future randomized control trials to understand the efficacy and risk of the use of early oral anticoagulation.

Supplemental Digital Content is available in the text., Objectives: Patients on extracorporeal support for severe acute respiratory distress syndrome may require a prolonged period of deep sedation. In these patients, volatile sedation may represent a valid alternative to IV drugs. The aim of our study was to describe the feasibility of volatile sedation in a large cohort of acute respiratory distress syndrome patients undergoing venovenous extracorporeal membrane oxygenation and ultraprotective ventilation. Design: Retrospective monocentric study. Setting: Adult ICU, ASST Monza, Italy. Patients: Adult patients who underwent volatile sedation with isoflurane during venovenous extracorporeal membrane oxygenation between 2009 and 2019. Interventions: Isoflurane was delivered via the AnaConDa system. The sedation level, hemodynamics, and laboratory tests were compared between the volatile sedation phase and the IV sedation phases before and after the isoflurane sedation period. Measurements and Main Results: About 74 patients (50 yr [43–56 yr]) were included. Median duration of venovenous extracorporeal membrane oxygenation support was 22 days (14–51 d). Volatile sedation started on day 3 (2–6) of extracorporeal membrane oxygenation support, and its median duration was 7 days (4–13 d), ranging from 1 to 38 days. A total of 970 venovenous extracorporeal membrane oxygenation days were analyzed. During the volatile phase, the sedation level was slightly deeper (bispectral index 39 ± 6) compared with the IV phase before and after isoflurane (42 ± 8 and 43 ± 9, respectively, p < 0.001). Requirements of fentanyl and remifentanyl were reduced during the volatile phase. Minor differences in hemodynamics were observed during volatile sedation: mean arterial pressure was lower (75 ± 13 vs 79 ± 14 and 80 ± 15; p < 0.001), whereas cardiac output was higher (8.5 ± 1.9 vs 7.9 ± 1.8 and 8.0 ± 1.8; p = 0.003). Aspartate aminotransferase levels were lower during the volatile sedation phases (p < 0.001), whereas alanine aminotransferase, triglycerides, and creatine phosphokinase were more altered during the IV sedation phase before isoflurane (p < 0.001). Conclusions: Volatile sedation represents an alternative to IV agents to achieve long-term deep sedation in critically ill patients on extracorporeal membrane oxygenation undergoing ultraprotective ventilation.

Supplemental Digital Content is available in the text., OBJECTIVES: To investigate rebound hyperthermia following targeted temperature management after cardiac arrest and its impact on functional outcome. DESIGN: Post hoc analysis. SETTING: Ten European ICUs. PATIENTS: Patients included in the time-differentiated therapeutic hypothermia in out-of-hospital cardiac arrest survivors trial treated with targeted temperature management at 33°C for 48 or 24 hours. Favorable functional outcome was defined as a Cerebral Performance Category of 1 or 2 at 6 months. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 338 included patients, 103 (30%) experienced rebound hyperthermia defined as a maximum temperature after targeted temperature management and rewarming exceeding 38.5°C. Using multivariate logistic regression analysis, increasing age (odds ratio, 0.97; 95% CI, 0.95–0.99; p = 0.02) and severe acute kidney injury within 72 hours of ICU admission (odds ratio, 0.35; 95% CI, 0.13–0.91; p = 0.03) were associated with less rebound hyperthermia, whereas male gender (odds ratio, 3.94; 95% CI, 1.34–11.57; p = 0.01), highest C-reactive protein value (odds ratio, 1.04; 95% CI, 1.01–1.07; p = 0.02), and use of mechanical chest compression during cardiopulmonary resuscitation (odds ratio, 2.00; 95% CI, 1.10–3.67; p = 0.02) were associated with more rebound hyperthermia. Patients with favorable functional outcome spent less time after rewarming over 38.5°C (2.5% vs 6.3%; p = 0.03), 39°C (0.14% vs 2.7%; p < 0.01), and 39.5°C (0.03% vs 0.71%; p < 0.01) when compared with others. Median time to rebound hyperthermia was longer in the unfavorable functional outcome group (33.2 hr; interquartile range, 14.3–53.0 hr vs 6.5 hr; interquartile range, 2.2–34.1; p < 0.01). In a predefined multivariate binary logistic regression model, rebound hyperthermia was associated with decreased odds of favorable functional outcome (odds ratio, 0.42; 95% CI, 0.22–0.79). CONCLUSIONS: One-third of targeted temperature management patients experience rebound hyperthermia, and it is more common in younger male patients with an aggravated inflammatory response and those treated with a mechanical chest compression device. Later onset of rebound hyperthermia and temperatures exceeding 38.5°C associate with unfavorable outcome.

Supplemental Digital Content is available in the text., OBJECTIVES: Involvement of clinical pharmacists in the ICU attenuates costs, avoids adverse drug events, and reduces morbidity and mortality. This survey assessed services and activities of ICU pharmacists. Design: A 27-question, pretested survey. SETTING: 1,220 U.S. institutions. Subjects: Critical care pharmacists. Interventions: Electronic questionnaire of pharmacy services and activities across clinical practice, education, scholarship, and administration. Measurements and Main Results: A total of 401 (response rate of 35.4%) surveys representing 493 ICUs were completed. Median daily ICU census was 12 (interquartile range, 6–20) beds with 1 (interquartile range, 1–1.5) pharmacist full-time equivalent per ICU. Direct clinical ICU pharmacy services were available in 70.8% of ICUs. Pharmacists attended rounds 5 days (interquartile range, 4–5 d) per week with a median patient-to-pharmacist ratio of 17 (interquartile range, 12–26). The typical workweek consisted of 50% (interquartile range, 40–60%) direct ICU patient care, 10% (interquartile range, 8–16%) teaching, 8% (interquartile range, 5–18%) order processing, 5% (interquartile range, 0–20%) direct non-ICU patient care, 5% (interquartile range, 2–10%) administration, 5% (interquartile range, 0–10%) scholarship, and 0% (interquartile range, 0–5%) drug distribution. Common clinical activities as a percentage of the workweek were reviewing drug histories (28.5%); assessing adverse events (27.6%); and evaluating (26.1%), monitoring (23.8%), and managing (21.4%) drug therapies. Services were less likely to occur overnight or on weekends. Telemedicine was rarely employed. Dependent prescriptive authority (per protocol or via practice agreements) was available to 51.1% of pharmacists and independent prescriptive authority was provided by 13.4% of pharmacists. Educational services most frequently provided were inservices (97.6%) and experiential training of students or residents (89%). Education of ICU healthcare members was provided at a median of 5 times/mo (interquartile range, 3–15 times/mo). Most respondents were involved with ICU or departmental policies/guidelines (84–86.8%) and 65.7% conducted some form of scholarship. Conclusions: ICU pharmacists have diverse and versatile responsibilities and provide several key clinical and nonclinical services. Initiatives to increase the availability of services are warranted.