What Are the Real Issues in Providing Extracorporeal Membrane Oxygenation (ECMO) Support: A Survey.

INTRODUCTION: By using a novel survey our study aimed to assess the challenges ECMO and Critical Care (CC) teams face when initiating and managing patient's ECMO support. METHODS: A qualitative survey-based observational study was performed of members of 2 Critical Care Medicine organizations involved in decision-making around the practice of Extracorporeal Membrane Oxygenation (ECMO). The range of exploratory questions covered ethical principles of informed consent, autonomy and goals of care discussions, beneficence, non-maleficence (offering life-sustaining treatments in end-of-life care), and justice (insurance-related limitations of treatment). Questions also covered pragmatic practice and quality improvement areas, such as exploring whether palliative care or ethics teams were involved in such decision-making. RESULTS: 305 members received the survey links, and a total of 61 completed surveys were received, for an overall response rate of 20% among all eligible members. Only 70% of the participants who manage ECMO patients are involved in the ECMO initiation decision process. The majority do not involve Ethics or Palliative care at the initial ECMO initiation decision step. Of the ethical and moral dilemmas reported, the majority revolved around 1. Prognostication of patients receiving VV and VA ECMO support, 2. Lack of knowledge of patient's wishes and goals, 3. Disconnect between expectations of families and outcomes and 4. Staff moral distress around when to stop ECMO in case of futility. CONCLUSION: Our survey highlights areas of distress and dilemma which have been stressed before in the initiation, management, and outcomes of ECMO patients, however with the increasing use of this modality of cardiopulmonary mechanical support being offered, the survey results can offer a guidance using sound ethical principles.

Essential right heart physiology for the perioperative practitioner POQI IX: current perspectives on the right heart in the perioperative period.

As patients continue to live longer from diseases that predispose them to right ventricular (RV) dysfunction or failure, many more patients will require surgery for acute or chronic health issues. Because RV dysfunction results in significant perioperative morbidity if not adequately assessed or managed, understanding appropriate assessment and treatments is important in preventing subsequent morbidity and mortality in the perioperative period. In light of the epidemiology of right heart disease, a working knowledge of right heart anatomy and physiology and an understanding of the implications of right-sided heart function for perioperative care are essential for perioperative practitioners. However, a significant knowledge gap exists concerning this topic. This manuscript is one part of a collection of papers from the PeriOperative Quality Initiative (POQI) IX Conference focusing on "Current Perspectives on the Right Heart in the Perioperative Period." This review aims to provide perioperative clinicians with an essential understanding of right heart physiology by answering five key questions on this topic and providing an explanation of seven fundamental concepts concerning right heart physiology.

Diagnosis and management of autoimmune diseases in the ICU.

Autoimmune diseases encompass a broad spectrum of disorders characterized by disturbed immunoregulation leading to the development of specific autoantibodies, resulting in inflammation and multiple organ involvement. A distinction should be made between connective tissue diseases (mainly systemic lupus erythematosus, systemic scleroderma, inflammatory muscle diseases, and rheumatoid arthritis) and vasculitides (mainly small-vessel vasculitis such as antineutrophil cytoplasmic antibody-associated vasculitis and immune-complex mediated vasculitis). Admission of patients with autoimmune diseases to the intensive care unit (ICU) is often triggered by disease flare-ups, infections, and organ failure and is associated with high mortality rates. Management of these patients is complex, including prompt disease identification, immunosuppressive treatment initiation, and life-sustaining therapies, and requires multi-disciplinary involvement. Data about autoimmune diseases in the ICU are limited and there is a need for multicenter, international collaboration to improve patients' diagnosis, management, and outcomes. The objective of this narrative review is to summarize the epidemiology, clinical features, and selected management of severe systemic autoimmune diseases.

Exploring phenotype-based ventilator parameter optimization to mitigate postoperative pulmonary complications: a retrospective observational cohort study.

PURPOSE: To identify tidal volume (VT) and positive end-expiratory pressure (PEEP) associated with the lowest incidence and severity of postoperative pulmonary complications (PPCs) for each phenotype based on preoperative characteristics. METHODS: The subjects of this retrospective observational cohort study were 34,910 adults who underwent surgery, using general anesthesia with mechanical ventilation. Initially, the least absolute shrinkage and selection operator regression was employed to select relevant preoperative characteristics. Then, the classification and regression tree (CART) was built to identify phenotypes. Finally, we computed the area under the receiver operating characteristic curves from logistic regressions to identify VT and PEEP associated with the lowest incidence and severity of PPCs for each phenotype. RESULTS: CARTs classified seven phenotypes for each outcome. A probability of the development of PPCs ranged from the lowest (3.51%) to the highest (68.57%), whereas the probability of the development of the highest level of PPC severity ranged from 3.3% to 91.0%. Across all phenotypes, the VT and PEEP associated with the most desirable outcomes were within a small range of VT 7-8 ml/kg predicted body weight with PEEP of between 6 and 8 cmH2O. CONCLUSIONS: The ranges of optimal VT and PEEP were small, regardless of the phenotypes, which had a wide range of risk profiles.

Epidemiology, Resistance Profiles, and Outcomes of Bloodstream Infections in Community-Onset Sepsis in the United States.

OBJECTIVES: To describe frequency of positive blood cultures, patterns of pathogens' characteristics and their resistance profile in patients with blood cultures drawn due to a presumed diagnosis of community-onset sepsis, and to examine the association between blood culture-positive pathogens and hospital mortality. DESIGN: Retrospective cohort study. SETTING: Two hundred one U.S. hospitals from 2016 to 2020 using the Premier Healthcare Database. SUBJECTS: Adult patients presenting with community-onset sepsis who had blood cultures collected within 2 days of hospital admission. We defined sepsis using the U.S. Centers for Disease Control Adult Sepsis Event Surveillance criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 147,061 patients with community-onset sepsis. The number of blood culture-positive sepsis episodes was 21,167 (14%) and the number of nonblood culture-positive sepsis episodes was 20,326 (14%). Among patients with blood culture-positive sepsis, Gram-negative rods were isolated in 55% of patients, Gram-positive cocci were isolated in 47%. Of those, methicillin-resistant Staphylococcus aureus (MRSA) was 11%, ceftriaxone-resistant Enterobacterales /extended-spectrum ß-lactamase was 7%, and carbapenem-resistant Enterobacterales was 1.3%. The crude in-hospital mortality was 17% for culture-negative sepsis, 13% for nonblood culture-positive sepsis, and 17% for blood culture-positive sepsis. In multilevel logistic regression models, compared with culture-negative sepsis, blood culture-positive sepsis (adjusted odds ratio [aOR], 0.89; 95% CI, 0.85-0.94) and nonblood culture-positive sepsis (aOR, 0.82; 95% CI, 0.78-0.87) were associated with lower odds of in-hospital mortality. Acinetobacter species, Pseudomonas aeruginosa , methicillin-sensitive Staphylococcus aureus , and MRSA were associated with higher in-hospital mortality, whereas Escherichia coli , Klebsiella species, Proteus species, and Streptococcus species were associated with lower in-hospital mortality. CONCLUSIONS: In patients hospitalized with community-onset sepsis, the prevalence of blood culture-positive sepsis was 14%. Among positive blood culture sepsis resistant organisms were infrequent. Compared with culture-negative sepsis, blood culture-positive sepsis and nonblood culture-positive sepsis were associated with lower in-hospital mortality.

Association of Appropriate Empirical Antimicrobial Therapy With In-Hospital Mortality in Patients With Bloodstream Infections in the US.

Importance: Bloodstream infections (BSIs) are a major public health problem associated with high morbidity. Little evidence exists regarding the epidemiology of BSIs and the use of appropriate empirical antimicrobial therapy. Objective: To estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality. Design, Setting, and Participants: This retrospective cross-sectional study used data from the Premier Healthcare database from 2016 to 2020. The analysis included 32 100 adult patients (aged ≥18 years) with BSIs from 183 US hospitals who received at least 1 new systemic antimicrobial agent within 2 days after blood samples were collected during the hospitalization. Patients with polymicrobial infections were excluded from the analysis. Exposures: Appropriate empirical therapy was defined as initiation of at least 1 new empirical antimicrobial agent to which the pathogen isolated from blood culture was susceptible either on the day of or the day after the blood sample was collected. Main Outcomes and Measures: Multilevel logistic regression models were used to estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality for patients infected with gram-negative rods (GNRs), gram-positive cocci (GPC), and Candida species. Results: Among 32 100 patients who had BSIs and received new empirical antimicrobial agents, the mean (SD) age was 64 (16) years; 54.8% were male, 69.9% were non-Hispanic White, and in-hospital mortality was 14.3%. The most common pathogens were Escherichia coli (58.4%) and Staphylococcus aureus (31.8%). Among patients infected with S aureus, methicillin-resistant S aureus was isolated in 43.6%. The crude proportions of appropriate empirical therapy use were 94.4% for GNR, 97.0% for GPC, and 65.1% for Candida species. The proportions of appropriate therapy use for resistant organisms were 55.3% for carbapenem-resistant Enterobacterales species and 60.4% for vancomycin-resistant Enterococcus species. Compared with inappropriate empirical therapy, receipt of appropriate empirical antimicrobial therapy was associated with lower in-hospital risk of death for 3 pathogen groups (GNR: adjusted odds ratio [aOR], 0.52 [95% CI, 0.42-0.64]; GPC: aOR, 0.60 [95% CI, 0.47-0.78]; Candida species: aOR, 0.43 [95% CI, 0.21-0.87]). Conclusions and Relevance: In this cross-sectional study of patients hospitalized with BSIs, receipt of appropriate initial empirical antimicrobial therapy was associated with lower in-hospital mortality. It is important for clinicians to carefully choose empirical antimicrobial agents to improve outcomes in patients with BSIs.

Postoperative Acute Kidney Injury by Age and Sex: A Retrospective Cohort Association Study.

BACKGROUND: Acute kidney injury (AKI) after noncardiac surgery is common and has substantial health impact. Preclinical and clinical studies examining the influence of sex on AKI have yielded conflicting results, although they typically do not account for age-related changes. The objective of the study was to determine the association of age and sex groups on postoperative AKI. The authors hypothesized that younger females would display lower risk of postoperative AKI than males of similar age, and the protection would be lost in older females. METHODS: This was a multicenter retrospective cohort study across 46 institutions between 2013 and 2019. Participants included adult inpatients without pre-existing end-stage kidney disease undergoing index major noncardiac, nonkidney/urologic surgeries. The authors' primary exposure was age and sex groups defined as females 50 yr or younger, females older than 50 yr, males 50 yr or younger, and males older than 50 yr. The authors' primary outcome was development of AKI by Kidney Disease-Improving Global Outcomes serum creatinine criteria. Exploratory analyses included associations of ascending age groups and hormone replacement therapy home medications with postoperative AKI. RESULTS: Among 390,382 patients, 25,809 (6.6%) developed postoperative AKI (females 50 yr or younger: 2,190 of 58,585 [3.7%]; females older than 50 yr: 9,320 of 14,4047 [6.5%]; males 50 yr or younger: 3,289 of 55,503 [5.9%]; males older than 50 yr: 11,010 of 132,447 [8.3%]). When adjusted for AKI risk factors, compared to females younger than 50 yr (odds ratio, 1), the odds of AKI were higher in females older than 50 yr (odds ratio, 1.51; 95% CI, 1.43 to 1.59), males younger than 50 yr (odds ratio, 1.90; 95% CI, 1.79 to 2.01), and males older than 50 yr (odds ratio, 2.06; 95% CI, 1.96 to 2.17). CONCLUSIONS: Younger females display a lower odds of postoperative AKI that gradually increases with age. These results suggest that age-related changes in women should be further studied as modifiers of postoperative AKI risk after noncardiac surgery.

The impact of race on utilization of durable left ventricular assist device therapy in patients with advanced heart failure.

BACKGROUND: Heart failure affects >6 million people in the United States alone and is most prevalent in Black patients who suffer the highest mortality risk. Yet prior studies have suggested that Black patients are less likely to receive advanced heart failure therapy. We hypothesized that Black patients would have decreased rates of durable left ventricular assist device (LVAD) implantation within our expansive heart failure program. METHODS: A retrospective single-center cohort study was conducted at a single high-volume academic medical center. Patients between 18 and 85 years admitted with a diagnosis of cardiogenic shock or congestive heart failure between 1, 2013 and 12, 2017 with a left ventricular ejection fraction < 30% and inotropic dependence or need for mechanical circulatory support were included. Patients with contraindications to durable LVAD were excluded. An adjusted logistic regression model for durable LVAD implantation within 90 days of the index admission was used to determine the effect of race on durable LVAD implantation. RESULTS: Among the 702 study patients (60.9% White, 34.1% Black), durable LVAD implantation was performed within 90 days of the index admission in 183 (26%) of the cohort. After multivariate analysis, Black patients were not found to have a statistically significant difference in durable LVAD implantation rates compared to White patients in our study (OR: 0.68 [95% confidence interval: 0.45-1.04; p: .074]). CONCLUSIONS: Black patients in our study did not have a statistically significant difference in the rate of durable LVAD implantation compared with White patients after adjustments were made for age, sex, socioeconomic, and clinical covariates. Larger prospective studies are needed to validate these findings.

No Association of Early Postoperative Heart Rate With Outcomes After Coronary Artery Bypass Grafting.

BACKGROUND: Elevated perioperative heart rate potentially causes perioperative myocardial injury because of imbalance in oxygen supply and demand. However, large multicenter studies evaluating early postoperative heart rate and major adverse cardiac and cerebrovascular events (MACCEs) are lacking. OBJECTIVE: To assess the associations of 4 postoperative heart rate assessment methods with in-hospital MACCEs after elective coronary artery bypass grafting (CABG). METHODS: Using data from the eICU Collaborative Research Database in the United States from 2014 to 2015, the study evaluated postoperative heart rate measured during hospitalization within 24 hours after intensive care unit admission. Four heart rate assessment methods were evaluated: maximum heart rate, duration above heart rate 100/min, area above heart rate 100/min, and time-weighted average heart rate. The outcome was in-hospital MACCEs, defined as a composite of in-hospital death, myocardial infarction, angina, arrhythmia, heart failure, stroke, cardiac arrest, or repeat revascularization. RESULTS: Among 2585 patients, the crude rate of in-hospital MACCEs was 6.2%. In multivariable logistic regression analysis, the adjusted odds ratios (95% CI) for in-hospital MAC-CEs assessed by maximum heart rate in each heart rate category (beats per minute: >100-110, >110-120, >120-130, and >130) were 1.43 (0.95-2.15), 0.98 (0.56-1.64), 1.47 (0.76-2.69), and 1.71 (0.80-3.35), respectively. Similarly, none of the other 3 methods were associated with MACCEs. CONCLUSIONS: More research is needed to assess the usefulness of heart rate measurement in patients after CABG.

Racial and Ethnic Differences in the Prevalence of Do-Not-Resuscitate Orders among Older Adults with Severe Traumatic Brain Injury.

BACKGROUND: Older adults suffering from traumatic brain injury (TBI) are subject to higher injury burden and mortality. Do Not Resuscitate (DNR) orders are used to provide care aligned with patient wishes, but they may not be equitably distributed across racial/ethnic groups. We examined racial/ethnic differences in the prevalence of DNR orders at hospital admission in older patients with severe TBI. METHODS: We conducted a retrospective cohort study using the National Trauma Databank (NTDB) between 2007 to 2016. We examined patients ≥ 65 years with severe TBI. For our primary aim, the exposure was race/ethnicity and outcome was the presence of a documented DNR at hospital admission. We conducted an exploratory analysis of hospital outcomes including hospital mortality, discharge to hospice, and healthcare utilization (intracranial pressure monitor placement, hospital LOS, and duration of mechanical ventilation). RESULTS: Compared to White patients, Black patients (OR 0.48, 95% CI 0.35-0.64), Hispanic patients (OR 0.54, 95% CI 0.40-0.70), and Asian patients (OR 0.63, 95% CI 0.44-0.90) had decreased odds of having a DNR order at hospital admission. Patients with DNRs had increased odds of hospital mortality (OR 2.16, 95% CI 1.94-2.42), discharge to hospice (OR 2.08, 95% CI 1.75-2.46), shorter hospital LOS (-2.07 days, 95% CI -3.07 to -1.08) and duration of mechanical ventilation (-1.09 days, 95% CI -1.52 to -0.67). There was no significant difference in the utilization of ICP monitoring (OR 0.94, 95% CI 0.78-1.12). CONCLUSIONS: We found significant racial and ethnic differences in the utilization of DNR orders among older patients with severe TBI. Additionally. DNR orders at hospital admission were associated with increased in-hospital mortality, increased hospice utilization, and decreased healthcare utilization. Future studies should examine mechanisms underlying race-based differences in DNR utilization.

Mechanical thrombectomy for perioperative ischemic stroke following elective inpatient surgery in the United States.

Perioperative ischemic stroke significantly increases morbidity and mortality in patients undergoing elective surgery. Mechanical thrombectomy can improve ischemic stroke outcomes, but frequency and trend of its utilization for treatment of perioperative ischemic stroke is not studied. We identified adults who underwent elective inpatient surgery from 2008 to 2018 and suffered from a perioperative ischemic stroke from the Premier Healthcare Database. The difference in mechanical thrombectomy usage before and after the updated recommendation inacute stroke guidelines was assessed in a univariate analysis using a chi-squared test. A segmented regression model was created to assess the change in rate over time.Of 6,349,668 patients with elective inpatient surgery, 12,507 (0.2%) had perioperative ischemic stroke. Mean age (and standard deviation) was 69.5 (11.7) years, and 48.8% were female. Mechanical thrombectomy was used in 1.7% patients and its use increased from 0.0% in 3rd quarter, 2008 to 4.4% in 4th quarter, 2018. Significant increase in the use of mechanical thrombectomy was seen after 3rd quarter, 2015 when its use was incorporated in acute stroke treatment guideline (1.14% before 3rd quarter, 2015 versus 3.07% after; p < 0.0001). Amongst patients with perioperative ischemic stroke, patients who received mechanical thrombectomy were more likely to have their surgery performed at a teaching institute (67.3% versus 53.9%). Although a significant increase in rates of utilization of mechanical thrombectomy was observed, rates of utilization remain low, especially in non-teaching hospitals. This highlights improvements in the management of perioperative ischemic strokes and further opportunities to improve outcomes.

Underutilization of Acetaminophen in Older Adult Trauma Patients.

INTRODUCTION: Older adults are more vulnerable to opioid-associated morbidity. The purpose of this study was to determine the frequency and timing of acetaminophen and opioid use in the postoperative period. METHODS: Older adult trauma patients (≥65 years) with hip fractures requiring femur or hip fixation were reviewed (Premier Database 2008-2014). We examined rates of acetaminophen use on the day of surgery and prior to receipt of oral opioids. Mixed-effects linear regression models were used to examine the effects of an acetaminophen-first approach on opioid use the day prior to and on the day of discharge. RESULTS: Of the 192 768 patients, 81.6% were Caucasian; 74.0% were female; and the mean age was 82.0 years [± 7.0]. Only 16.8% (32 291) of patients received acetaminophen prior to being prescribed opioids. 27.4% (52 779) received an acetaminophen-opioid combination, and 9.2% (17 730) received opioids without acetaminophen first. Acetaminophen first was associated with reduced opioid use on the day prior to and on the day of discharge (3.52 parenteral morphine equivalent doses (PMEs) less [95% CI: 3.33, 3.70]; P < .0001). A statistically but not clinically significant reduction in length of stay was observed in the acetaminophen-first group. CONCLUSION: Nearly 37% of older adult patients did not receive acetaminophen as first-line analgesia after hip surgery. Multimodal analgesia, including non-opioid medications as first-line, should be encouraged.

Association Between Gabapentinoids and Postoperative Pulmonary Complications in Patients Undergoing Thoracic Surgery.

OBJECTIVE: Perioperative gabapentinoids in general surgery have been associated with an increased risk of postoperative pulmonary complications (PPCs), while resulting in equivocal pain relief. This study's aim was to examine the utilization of gabapentinoids in thoracic surgery to determine the association of gabapentinoids with PPCs and perioperative opioid utilization. DESIGN: A multicenter retrospective cohort study. SETTING: Hospitals in the Premier Healthcare Database from 2012 to 2018. PARTICIPANTS: A total of 70,336 patients undergoing elective open thoracotomy, video-assisted thoracic surgery, and robotic-assisted thoracic surgery. INTERVENTIONS: Propensity score analyses were used to assess the association between gabapentinoids on day of surgery and the primary composite outcome of PPCs, defined as respiratory failure, pneumonia, reintubation, pulmonary edema, and noninvasive and invasive ventilation. Secondary outcomes included invasive and noninvasive ventilation, hospital mortality, length of stay, opioid consumption on day of surgery, and average daily opioid consumption after day of surgery. RESULTS: Overall, 8,142 (12%) patients received gabapentinoids. The prevalence of gabapentin on day of surgery increased from 3.8% in 2012 to 15.9% in 2018. Use of gabapentinoids on day of surgery was associated with greater odds of PPCs (odds ratio [OR] 1.19, 95% CI 1.11-1.28), noninvasive mechanical ventilation (OR 1.30, 95% CI 1.16-1.45), and invasive mechanical ventilation (OR 1.14, 95% CI 1.02-1.28). Secondary outcomes indicated no clinically meaningful associations of gabapentinoid use with opioid consumption, hospital mortality, or length of stay. CONCLUSIONS: Perioperative gabapentinoid administration in elective thoracic surgery may be associated with a higher risk of PPCs and no opioid-sparing effect.

Clinical Data Extraction During Public Health Emergencies: A Blockchain Technology Assessment.

OBJECTIVE: We sought to explore the technical and legal readiness of healthcare institutions for novel data-sharing methods that allow clinical information to be extracted from electronic health records (EHRs) and submitted securely to the Food and Drug Administration's (FDA's) blockchain through a secure data broker (SDB). MATERIALS AND METHODS: This assessment was divided into four sections: an institutional EHR readiness assessment, legal consultation, institutional review board application submission, and a test of healthcare data transmission over a blockchain infrastructure. RESULTS: All participating institutions reported the ability to electronically extract data from EHRs for research. Formal legal agreements were deemed unnecessary to the project but would be needed in future tests of real patient data exchange. Data transmission to the FDA blockchain met the success criteria of data connection from within the four institutions' firewalls, externally to the FDA blockchain via a SDB. DISCUSSION: The readiness survey indicated advanced analytic capability in hospital institutions and highlighted inconsistency in Fast Healthcare Interoperability Resources format utilitzation across institutions, despite requirements of the 21st Century Cures Act. Further testing across more institutions and annual exercises leveraging the application of data exchange over a blockchain infrastructure are recommended actions for determining the feasibility of this approach during a public health emergency and broaden the understanding of technical requirements for multisite data extraction. CONCLUSION: The FDA's RAPID (Real-Time Application for Portable Interactive Devices) program, in collaboration with Discovery, the Critical Care Research Network's PREP (Program for Resilience and Emergency Preparedness), identified the technical and legal challenges and requirements for rapid data exchange to a government entity using the FDA blockchain infrastructure.

Variation in Early Management Practices in Moderate-to-Severe ARDS in the United States: The Severe ARDS: Generating Evidence Study.

BACKGROUND: Although specific interventions previously demonstrated benefit in patients with ARDS, use of these interventions is inconsistent, and patient mortality remains high. The impact of variability in center management practices on ARDS mortality rates remains unknown. RESEARCH QUESTION: What is the impact of treatment variability on mortality in patients with moderate to severe ARDS in the United States? STUDY DESIGN AND METHODS: We conducted a multicenter, observational cohort study of mechanically ventilated adults with ARDS and Pao2 to Fio2 ratio of ≤ 150 with positive end-expiratory pressure of ≥ 5 cm H2O, who were admitted to 29 US centers between October 1, 2016, and April 30, 2017. The primary outcome was 28-day in-hospital mortality. Center variation in ventilator management, adjunctive therapy use, and mortality also were assessed. RESULTS: A total of 2,466 patients were enrolled. Median baseline Pao2 to Fio2 ratio was 105 (interquartile range, 78.0-129.0). In-hospital 28-day mortality was 40.7%. Initial adherence to lung protective ventilation (LPV; tidal volume, ≤ 6.5 mL/kg predicted body weight; plateau pressure, or when unavailable, peak inspiratory pressure, ≤ 30 mm H2O) was 31.4% and varied between centers (0%-65%), as did rates of adjunctive therapy use (27.1%-96.4%), methods used (neuromuscular blockade, prone positioning, systemic steroids, pulmonary vasodilators, and extracorporeal support), and mortality (16.7%-73.3%). Center standardized mortality ratios (SMRs), calculated using baseline patient-level characteristics to derive expected mortality rate, ranged from 0.33 to 1.98. Of the treatment-level factors explored, only center adherence to early LPV was correlated with SMR. INTERPRETATION: Substantial center-to-center variability exists in ARDS management, suggesting that further opportunities for improving ARDS outcomes exist. Early adherence to LPV was associated with lower center mortality and may be a surrogate for overall quality of care processes. Future collaboration is needed to identify additional treatment-level factors influencing center-level outcomes. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03021824; URL: www.clinicaltrials.gov.

Association of Early Multiple Organ Dysfunction With Clinical and Functional Outcomes Over the Year Following Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study.

OBJECTIVES: Traumatic brain injury is a leading cause of death and disability in the United States. While the impact of early multiple organ dysfunction syndrome has been studied in many critical care paradigms, the clinical impact of early multiple organ dysfunction syndrome in traumatic brain injury is poorly understood. We examined the incidence and impact of early multiple organ dysfunction syndrome on clinical, functional, and disability outcomes over the year following traumatic brain injury. DESIGN: Retrospective cohort study. SETTING: Patients enrolled in the Transforming Clinical Research and Knowledge in Traumatic Brain Injury study, an 18-center prospective cohort study of traumatic brain injury patients evaluated in participating level 1 trauma centers. SUBJECTS: Adult (age > 17 yr) patients with moderate-severe traumatic brain injury (Glasgow Coma Scale < 13). We excluded patients with major extracranial injury (Abbreviated Injury Scale score ≥ 3). INTERVENTIONS: Development of early multiple organ dysfunction syndrome, defined as a maximum modified Sequential Organ Failure Assessment score greater than 7 during the initial 72 hours following admission. MEASUREMENTS AND MAIN RESULTS: The main outcomes were: hospital mortality, length of stay, 6-month functional and disability domains (Glasgow Outcome Scale-Extended and Disability Rating Scale), and 1-year mortality. Secondary outcomes included: ICU length of stay, 3-month Glasgow Outcome Scale-Extended, 3-month Disability Rating Scale, 1-year Glasgow Outcome Scale-Extended, and 1-year Disability Rating Scale. We examined 373 subjects with moderate-severe traumatic brain injury. The mean (sd) Glasgow Coma Scale in the emergency department was 5.8 (3.2), with 280 subjects (75%) classified as severe traumatic brain injury (Glasgow Coma Scale 3-8). Among subjects with moderate-severe traumatic brain injury, 252 (68%) developed early multiple organ dysfunction syndrome. Subjects that developed early multiple organ dysfunction syndrome had a 75% decreased odds of a favorable outcome (Glasgow Outcome Scale-Extended 5-8) at 6 months (adjusted odds ratio, 0.25; 95% CI, 0.12-0.51) and increased disability (higher Disability Rating Scale score) at 6 months (adjusted mean difference, 2.04; 95% CI, 0.92-3.17). Subjects that developed early multiple organ dysfunction syndrome experienced an increased hospital length of stay (adjusted mean difference, 11.4 d; 95% CI, 7.1-15.8), with a nonsignificantly decreased survival to hospital discharge (odds ratio, 0.47; 95% CI, 0.18-1.2). CONCLUSIONS: Early multiple organ dysfunction following moderate-severe traumatic brain injury is common and independently impacts multiple domains (mortality, function, and disability) over the year following injury. Further research is necessary to understand underlying mechanisms, improve early recognition, and optimize management strategies.