Showing papers in "Critical Care Medicine in 2020"

Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19).

Abstract: BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.

Coagulopathy of Coronavirus Disease 2019.

Abstract: OBJECTIVES: Recent studies have reported a high prevalence of thrombotic events in coronavirus disease 2019. However, the significance of thromboembolic complications has not been widely appreciated. The purpose of this review is to provide current knowledge of this serious problem. DESIGN: Narrative review. DATA SOURCES: Online search of published medical literature through PubMed using the term "COVID-19," "SARS," "acute respiratory distress syndrome," "coronavirus," "coagulopathy," "thrombus," and "anticoagulants." STUDY SELECTION AND DATA EXTRACTION: Articles were chosen for inclusion based on their relevance to coagulopathy and thrombosis in coronavirus disease 2019, and anticoagulant therapy. Reference lists were reviewed to identify additional relevant articles. DATA SYNTHESIS: Coronavirus disease 2019 is associated with a strikingly high prevalence of coagulopathy and venous thromboembolism that may contribute to respiratory deterioration. Monitoring coagulation variables is important, as abnormal coagulation tests are related to adverse outcomes and may necessitate adjuvant antithrombotic interventions. In the initial phase of the infection, D-dimer and fibrinogen levels are increased, while activated partial prothrombin time, prothrombin time, and platelet counts are often relatively normal. Increased D-dimer levels three times the upper limit of normal may trigger screening for venous thromboembolism. In all hospitalized patients, thromboprophylaxis using low-molecular-weight heparin is currently recommended. The etiology of the procoagulant responses is complex and thought to be a result of specific interactions between host defense mechanisms and the coagulation system. Although the coagulopathy is reminiscent of disseminated intravascular coagulation and thrombotic microangiopathy, it has features that are markedly distinct from these entities. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019 frequently induces hypercoagulability with both microangiopathy and local thrombus formation, and a systemic coagulation defect that leads to large vessel thrombosis and major thromboembolic complications, including pulmonary embolism in critically ill hospitalized patients. D-dimers and fibrinogen levels should be monitored, and all hospitalized patients should undergo thromboembolism prophylaxis with an increase in therapeutic anticoagulation in certain clinical situations.

ICU and Ventilator Mortality Among Critically Ill Adults With Coronavirus Disease 2019.

Abstract: Objectives To determine mortality rates among adults with critical illness from coronavirus disease 2019. Design Observational cohort study of patients admitted from March 6, 2020, to April 17, 2020. Setting Six coronavirus disease 2019 designated ICUs at three hospitals within an academic health center network in Atlanta, Georgia, United States. Patients Adults greater than or equal to 18 years old with confirmed severe acute respiratory syndrome-CoV-2 disease who were admitted to an ICU during the study period. Interventions None. Measurements and main results Among 217 critically ill patients, mortality for those who required mechanical ventilation was 35.7% (59/165), with 4.8% of patients (8/165) still on the ventilator at the time of this report. Overall mortality to date in this critically ill cohort is 30.9% (67/217) and 60.4% (131/217) patients have survived to hospital discharge. Mortality was significantly associated with older age, lower body mass index, chronic renal disease, higher Sequential Organ Failure Assessment score, lower PaO2/FIO2 ratio, higher D-dimer, higher C-reactive protein, and receipt of mechanical ventilation, vasopressors, renal replacement therapy, or vasodilator therapy. Conclusions Despite multiple reports of mortality rates exceeding 50% among critically ill adults with coronavirus disease 2019, particularly among those requiring mechanical ventilation, our early experience indicates that many patients survive their critical illness.

Early Prediction of Sepsis From Clinical Data: The PhysioNet/Computing in Cardiology Challenge 2019.

Abstract: Objectives Sepsis is a major public health concern with significant morbidity, mortality, and healthcare expenses. Early detection and antibiotic treatment of sepsis improve outcomes. However, although professional critical care societies have proposed new clinical criteria that aid sepsis recognition, the fundamental need for early detection and treatment remains unmet. In response, researchers have proposed algorithms for early sepsis detection, but directly comparing such methods has not been possible because of different patient cohorts, clinical variables and sepsis criteria, prediction tasks, evaluation metrics, and other differences. To address these issues, the PhysioNet/Computing in Cardiology Challenge 2019 facilitated the development of automated, open-source algorithms for the early detection of sepsis from clinical data. Design Participants submitted containerized algorithms to a cloud-based testing environment, where we graded entries for their binary classification performance using a novel clinical utility-based evaluation metric. We designed this scoring function specifically for the Challenge to reward algorithms for early predictions and penalize them for late or missed predictions and for false alarms. Setting ICUs in three separate hospital systems. We shared data from two systems publicly and sequestered data from all three systems for scoring. Patients We sourced over 60,000 ICU patients with up to 40 clinical variables for each hour of a patient's ICU stay. We applied Sepsis-3 clinical criteria for sepsis onset. Interventions None. Measurements and main results A total of 104 groups from academia and industry participated, contributing 853 submissions. Furthermore, 90 abstracts based on Challenge entries were accepted for presentation at Computing in Cardiology. Conclusions Diverse computational approaches predict the onset of sepsis several hours before clinical recognition, but generalizability to different hospital systems remains a challenge.

Management of Acute Ischemic Stroke.

Abstract: Objectives Concise "synthetic" review of the state of the art of management of acute ischemic stroke. Data sources Available literature on PubMed. Study selection We selected landmark studies, recent clinical trials, observational studies, and professional guidelines on the management of stroke including the last 10 years. Data extraction Eligible studies were identified and results leading to guideline recommendations were summarized. Data synthesis Stroke mortality has been declining over the past 6 decades, and as a result, stroke has fallen from the second to the fifth leading cause of death in the United States. This trend may follow recent advances in the management of stroke, which highlight the importance of early recognition and early revascularization. Recent studies have shown that early recognition, emergency interventional treatment of acute ischemic stroke, and treatment in dedicated stroke centers can significantly reduce stroke-related morbidity and mortality. However, stroke remains the second leading cause of death worldwide and the number one cause for acquired long-term disability, resulting in a global annual economic burden. Conclusions Appropriate treatment of ischemic stroke is essential in the reduction of mortality and morbidity. Management of stroke involves a multidisciplinary approach that starts and extends beyond hospital admission.

Acute Physiology and Chronic Health Evaluation II Score as a Predictor of Hospital Mortality in Patients of Coronavirus Disease 2019.

Abstract: Objectives Coronavirus disease 2019 has emerged as a major global health threat with a great number of deaths in China. We aimed to assess the association between Acute Physiology and Chronic Health Evaluation II score and hospital mortality in patients with coronavirus disease 2019, and to compare the predictive ability of Acute Physiology and Chronic Health Evaluation II score, with Sequential Organ Failure Assessment score and Confusion, Urea, Respiratory rate, Blood pressure, Age 65 (CURB65) score. Design Retrospective observational cohort. Setting Tongji Hospital in Wuhan, China. Subjects Confirmed patients with coronavirus disease 2019 hospitalized in the ICU of Tongji hospital from January 10, 2020, to February 10, 2020. Interventions None. Measurements and main results Of 178 potentially eligible patients with symptoms of coronavirus disease 2019, 23 patients (12.92%) were diagnosed as suspected cases, and one patient (0.56%) suffered from cardiac arrest immediately after admission. Ultimately, 154 patients were enrolled in the analysis and 52 patients (33.77%) died. Mean Acute Physiology and Chronic Health Evaluation II score (23.23 ± 6.05) was much higher in deaths compared with the mean Acute Physiology and Chronic Health Evaluation II score of 10.87 ± 4.40 in survivors (p Conclusions Acute Physiology and Chronic Health Evaluation II score was an effective clinical tool to predict hospital mortality in patients with coronavirus disease 2019 compared with Sequential Organ Failure Assessment score and CURB65 score. Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 serves as an early warning indicator of death and may provide guidance to make further clinical decisions.

Development and Reporting of Prediction Models: Guidance for Authors From Editors of Respiratory, Sleep, and Critical Care Journals.

Abstract: Prediction models aim to use available data to predict a health state or outcome that has not yet been observed. Prediction is primarily relevant to clinical practice, but is also used in research, and administration. While prediction modeling involves estimating the relationship between patient factors and outcomes, it is distinct from casual inference. Prediction modeling thus requires unique considerations for development, validation, and updating. This document represents an effort from editors at 31 respiratory, sleep, and critical care medicine journals to consolidate contemporary best practices and recommendations related to prediction study design, conduct, and reporting. Herein, we address issues commonly encountered in submissions to our various journals. Key topics include considerations for selecting predictor variables, operationalizing variables, dealing with missing data, the importance of appropriate validation, model performance measures and their interpretation, and good reporting practices. Supplemental discussion covers emerging topics such as model fairness, competing risks, pitfalls of "modifiable risk factors", measurement error, and risk for bias. This guidance is not meant to be overly prescriptive; we acknowledge that every study is different, and no set of rules will fit all cases. Additional best practices can be found in the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines, to which we refer readers for further details.

Potential for Lung Recruitment and Ventilation-Perfusion Mismatch in Patients With the Acute Respiratory Distress Syndrome From Coronavirus Disease 2019

Abstract: Objectives Severe cases of coronavirus disease 2019 develop the acute respiratory distress syndrome, requiring admission to the ICU. This study aimed to describe specific pathophysiological characteristics of acute respiratory distress syndrome from coronavirus disease 2019. Design Prospective crossover physiologic study. Setting ICU of a university-affiliated hospital from northern Italy dedicated to care of patients with confirmed diagnosis of coronavirus disease 2019. Patients Ten intubated patients with acute respiratory distress syndrome and confirmed diagnosis of coronavirus disease 2019. Interventions We performed a two-step positive end-expiratory pressure trial with change of 10 cm H2O in random order. Measurements and main results At each positive end-expiratory pressure level, we assessed arterial blood gases, respiratory mechanics, ventilation inhomogeneity, and potential for lung recruitment by electrical impedance tomography. Potential for lung recruitment was assessed by the recently described recruitment to inflation ratio. In a subgroup of seven paralyzed patients, we also measured ventilation-perfusion mismatch at lower positive end-expiratory pressure by electrical impedance tomography. At higher positive end-expiratory pressure, respiratory mechanics did not change significantly: compliance remained relatively high with low driving pressure. Oxygenation and ventilation inhomogeneity improved but arterial CO2 increased despite unchanged respiratory rate and tidal volume. The recruitment to inflation ratio presented median value higher than previously reported in acute respiratory distress syndrome patients but with large variability (median, 0.79 [0.53-1.08]; range, 0.16-1.40). The FIO2 needed to obtain viable oxygenation at lower positive end-expiratory pressure was significantly correlated with the recruitment to inflation ratio (r = 0.603; p = 0.05). The ventilation-perfusion mismatch was elevated (median, 34% [32-45%] of lung units) and, in six out of seven patients, ventilated nonperfused units represented a much larger proportion than perfused nonventilated ones. Conclusions In patients with acute respiratory distress syndrome from coronavirus disease 2019, potential for lung recruitment presents large variability, while elevated dead space fraction may be a specific pathophysiological trait. These findings may guide selection of personalized mechanical ventilation settings.

Society of Critical Care Medicine's International Consensus Conference on Prediction and Identification of Long-Term Impairments After Critical Illness.

Abstract: Background: After critical illness, new or worsening impairments in physical, cognitive, and/or mental health function are common among patients who have survived. Who should be screened for long-term impairments, what tools to use, and when remain unclear. Objectives: Provide pragmatic recommendations to clinicians caring for adult survivors of critical illness related to screening for postdischarge impairments. Participants: Thirty-one international experts in risk-stratification and assessment of survivors of critical illness, including practitioners involved in the Society of Critical Care Medicine’s Thrive Post-ICU Collaboratives, survivors of critical illness, and clinical researchers. Design: Society of Critical Care Medicine consensus conference on post-intensive care syndrome prediction and assessment, held in Dallas, in May 2019. A systematic search of PubMed and the Cochrane Library was conducted in 2018 and updated in 2019 to complete an original systematic review and to identify pre-existing systematic reviews. Meeting Outcomes: We concluded that existing tools are insufficient to reliably predict post-intensive care syndrome. We identified factors before (e.g., frailty, preexisting functional impairments), during (e.g., duration of delirium, sepsis, acute respiratory distress syndrome), and after (e.g., early symptoms of anxiety, depression, or post-traumatic stress disorder) critical illness that can be used to identify patients at high-risk for cognitive, mental health, and physical impairments after critical illness in whom screening is recommended. We recommend serial assessments, beginning within 2–4 weeks of hospital discharge, using the following screening tools: Montreal Cognitive Assessment test; Hospital Anxiety and Depression Scale; Impact of Event Scale-Revised (post-traumatic stress disorder); 6-minute walk; and/or the EuroQol-5D-5L, a health-related quality of life measure (physical function). Conclusions: Beginning with an assessment of a patient’s pre-ICU functional abilities at ICU admission, clinicians have a care coordination strategy to identify and manage impairments across the continuum. As hospital discharge approaches, clinicians should use brief, standardized assessments and compare these results to patient’s pre-ICU functional abilities (“functional reconciliation”). We recommend serial assessments for post-intensive care syndrome-related problems continue within 2–4 weeks of hospital discharge, be prioritized among high-risk patients, using the identified screening tools to prompt referrals for services and/or more detailed assessments.

The Epidemiology of Sepsis in Chinese ICUs: A National Cross-Sectional Survey.

Abstract: Objectives We performed a national cross-sectional survey to determine the epidemiologic characteristics of patients with sepsis in ICU in China. Design A cross-section survey study. Setting Forty-four hospitals in mainland China from December 1, 2015, to January 31, 2016. Patients All septic patients diagnosed according sepsis-1 criteria admitted to participating ICU. Interventions None. Measurements and main results We recorded demographic, physiologic, and microbiological data with follow-up for 90 days or death, if sooner. The frequency of sepsis and 90-day mortality rate were computed, and the relationship with gross domestic product determined. Multivariate logistic regression analysis was used to determine risk factors for 90-day mortality in patients with sepsis. Two-thousand three-hundred twenty-two patients with sepsis were included in the analysis, of whom 786 patients (33.9%) had hospital-acquired sepsis. The most common infection site was the lung (68.2%), followed by abdomen (26.6%) and bloodstream (7.8%). The frequency of sepsis in the ICU was 20.6 cases per 100 ICU admissions (95% CI, 15.8-25.4) with a 90-day mortality of 35.5%. The proportion of sepsis, severe sepsis, and septic shock were 3.10%, 43.6%, and 53.3% with a 90-day mortality of 2.78%, 17.69%, and 51.94%, respectively. Older age, low body weight, higher Sequential Organ Failure Assessment score, the number of systemic inflammatory response syndrome criteria, comorbid with heart failure, hematologic cancer, immunosuppression, higher level of lactate, infection site (pneumonia and bloodstream) were associated with 90-day mortality. Conclusions Sepsis affects a fifth of patients admitted to ICUs in mainland China with a 90-day mortality rate of 35.5%. Our findings indicate that a large burden of sepsis, and we need to focus on sepsis as a quality improvement target in China given the high mortality. In addition, further studies are needed to delineate the epidemiology of sepsis outside the ICU.

Corticosteroids as Adjunctive Therapy in the Treatment of Influenza: An Updated Cochrane Systematic Review and Meta-analysis.

Abstract: Objectives Corticosteroids may be beneficial in sepsis, but uncertainty remains over their effects in severe influenza. This systematic review updates the current evidence regarding corticosteroids in the treatment of influenza and examines the effect of dose on outcome. Data sources Electronic databases (MEDLINE, EMBASE, CINAHL, LILACS, CENTRAL, and Web of Science) and trial registries were searched to October 2018 for randomized controlled trials, quasi-experimental designs, and observational cohort studies reporting corticosteroid versus no corticosteroid treatment in individuals with influenza. Study selection and data extraction Two researchers independently assessed studies for inclusion. Risk of bias was assessed using the Cochrane Risk of Bias tool (randomized controlled trials) or Newcastle-Ottawa Scale (observational studies). Where appropriate, we estimated the effect of corticosteroids by random-effects meta-analyses using the generic inverse variance method. Meta-regression analysis was used to assess the association of corticosteroid dose and mortality. Data synthesis We identified 30 eligible studies, all observational apart from one randomized controlled trial. Twenty-one observational studies were included in the meta-analysis of mortality, which suggested an adverse association with corticosteroid therapy (odds ratio, 3.90; 95% CI, 2.31-6.60; 15 studies; adjusted hazard ratio, 1.49; 95% CI, 1.09-2.02; six studies). Risk of bias assessment was consistent with potential confounding by indication. Pooled analysis of seven studies showed increased odds of hospital-acquired infection in people treated with corticosteroids (unadjusted odds ratio, 2.74; 95% CI, 1.51-4.95). Meta-regression of the effect of dose on mortality did not reveal an association, but reported doses of corticosteroids in included studies were high (mostly > 40 mg methylprednisolone [or equivalent] per day). Conclusions Corticosteroid treatment in influenza is associated with increased mortality and hospital-acquired infection, but the evidence relates mainly to high corticosteroid doses and is of low quality with potential confounding by indication a major concern.

Sepsis Among Medicare Beneficiaries: 1. The Burdens of Sepsis, 2012–2018*

Abstract: Objectives To provide contemporary estimates of the burdens (costs and mortality) associated with acute inpatient Medicare beneficiary admissions for sepsis. Design Analysis of paid Medicare claims via the Centers for Medicare & Medicaid Services DataLink Project. Setting All U.S. acute care hospitals, excluding federally operated hospitals (Veterans Administration and Defense Health Agency). Patients All Medicare beneficiaries, 2012-2018, with an inpatient admission including one or more explicit sepsis codes. Interventions None. Measurements and main results Total inpatient hospital and skilled nursing facility admission counts, costs, and mortality over time. From calendar year (CY)2012-CY2018, the total number of Medicare Part A/B (fee-for-service) beneficiaries with an inpatient hospital admission associated with an explicit sepsis code rose from 811,644 to 1,136,889. The total cost of inpatient hospital admission including an explicit sepsis code for those beneficiaries in those calendar years rose from $17,792,657,303 to $22,439,794,212. The total cost of skilled nursing facility care in the 90 days subsequent to an inpatient hospital discharge that included an explicit sepsis code for Medicare Part A/B rose from $3,931,616,160 to $5,623,862,486 over that same interval. Precise costs are not available for Medicare Part C (Medicare Advantage) patients. Using available federal data sources, we estimated the aggregate cost of inpatient admissions and skilled nursing facility admissions for Medicare Advantage patients to have risen from $6.0 to $13.4 billion over the CY2012-CY2018 interval. Combining data for fee-for-service beneficiaries and estimates for Medicare Advantage beneficiaries, we estimate the total inpatient admission sepsis cost and any subsequent skilled nursing facility admission for all (fee-for-service and Medicare Advantage) Medicare patients to have risen from $27.7 to $41.5 billion. Contemporary 6-month mortality rates for Medicare fee-for-service beneficiaries with a sepsis inpatient admission remain high: for septic shock, approximately 60%; for severe sepsis, approximately 36%; for sepsis attributed to a specific organism, approximately 31%; and for unspecified sepsis, approximately 27%. Conclusion Sepsis remains common, costly to treat, and presages significant mortality for Medicare beneficiaries.

Routine Venous Thromboembolism Prophylaxis May Be Inadequate in the Hypercoagulable State of Severe Coronavirus Disease 2019.

Abstract: OBJECTIVES: The aim of this study was to determine the frequency of venous thromboembolism in critically ill coronavirus disease 2019 patients and associate a degree of inflammatory marker elevation to venous thromboembolism development. DESIGN: An observational study that identified patients with severe coronavirus disease 2019 between March 12, 2020, and March 31, 2020. Data reported are those available through May 6, 2020. SETTING: A multicenter study including three Indianapolis area academic hospitals. PATIENTS: Two-hundred forty consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 infection were admitted to one of three hospitals. One-hundred nine critically ill coronavirus disease 2019 patients admitted to the ICU were included in the analysis. INTERVENTIONS: All patients received routine subcutaneous chemical venous thromboembolism prophylaxis. MEASUREMENTS AND MAIN RESULTS: The primary outcome of this study was to determine the frequency of venous thromboembolism and the degree of inflammatory and coagulation marker elevation associated with venous thromboembolism development. Descriptive statistics outlined the frequency of venous thromboembolism at any time during severe coronavirus disease 2019. Clinical course and laboratory metrics were compared between patients that developed venous thromboembolism and patients that did not develop venous thromboembolism. Hypercoagulable thromboelastography was defined as two or more hypercoagulable parameters. MAIN RESULTS: One-hundred nine patients developed severe coronavirus disease 2019 requiring ICU care. The mean (± SD) age was 61 ± 16 years and 57% were male. Seventy-five patients (69%) were discharged home, 7 patients (6%) remain in the hospital, and 27 patients (25%) died. Venous thromboembolism was diagnosed in 31 patients (28%) 8 ± 7 days after hospital admission, including two patients diagnosed with venous thromboembolism at presentation to the hospital. Elevated admission D-dimer and peak D-dimer were associated with venous thromboembolism development (p < 0.05). D-dimer greater than 2,600 ng/mL predicted venous thromboembolism with an area under the receiver operating characteristic curve of 0.760 (95% CI, 0.661-0.858; p < 0.0001), sensitivity of 89.7%, and specificity of 59.5%. Twelve patients (11%) had thromboelastography performed and 58% of these patients had a hypercoagulable study. The calculated coagulation index was hypercoagulable in 50% of patients with thromboelastography. CONCLUSIONS: These data show that coronavirus disease 2019 results in a hypercoagulable state. Routine chemical venous thromboembolism prophylaxis may be inadequate in preventing venous thromboembolism in severe coronavirus disease 2019.

Critical Care Bed Capacity in Asian Countries and Regions.

Abstract: Objective To assess the number of adult critical care beds in Asian countries and regions in relation to population size. Design Cross-sectional observational study. Setting Twenty-three Asian countries and regions, covering 92.1% of the continent's population. Participants Ten low-income and lower-middle-income economies, five upper-middle-income economies, and eight high-income economies according to the World Bank classification. Interventions Data closest to 2017 on critical care beds, including ICU and intermediate care unit beds, were obtained through multiple means, including government sources, national critical care societies, colleges, or registries, personal contacts, and extrapolation of data. Measurements and main results Cumulatively, there were 3.6 critical care beds per 100,000 population. The median number of critical care beds per 100,000 population per country and region was significantly lower in low- and lower-middle-income economies (2.3; interquartile range, 1.4-2.7) than in upper-middle-income economies (4.6; interquartile range, 3.5-15.9) and high-income economies (12.3; interquartile range, 8.1-20.8) (p = 0.001), with a large variation even across countries and regions of the same World Bank income classification. This number was independently predicted by the World Bank income classification on multivariable analysis, and significantly correlated with the number of acute hospital beds per 100,000 population (r = 0.19; p = 0.047), the universal health coverage service coverage index (r = 0.35; p = 0.003), and the Human Development Index (r = 0.40; p = 0.001) on univariable analysis. Conclusions Critical care bed capacity varies widely across Asia and is significantly lower in low- and lower-middle-income than in upper-middle-income and high-income countries and regions.

Fluid Overload and Mortality in Adult Critical Care Patients-A Systematic Review and Meta-Analysis of Observational Studies.

Abstract: OBJECTIVE Fluid administration in combination with the increase in vasopermeability induced by critical illness often results in significant fluid overload in critically ill patients. Recent research indicates that mortality is increased in patients who have received large volumes of fluids. We have systematically reviewed and synthesized the evidence on fluid overload and mortality in critically ill patients and have performed a meta-analysis of available data from observational studies. DATA SOURCES A systematic search was performed on PubMed, EmBase, and the Cochrane Library databases. STUDY SELECTION AND DATA EXTRACTION All studies were eligible that investigated the impact of fluid overload (defined by weight gain > 5%) or positive cumulative fluid balance on mortality in adult critical care patients. We excluded animal studies and trials in pediatric populations (age < 16 years old), pregnant women, noncritically ill patients, very specific subpopulations of critically ill patients, and on early goal-directed therapy. Randomized controlled trials were only evaluated in the section on systematic review. Assessment followed the Cochrane/meta-analysis of observational trials in epidemiology guidelines for systematic reviews. DATA SYNTHESIS A total of 31 observational and three randomized controlled trials including 31,076 ICU patients met the inclusion criteria. Only observational studies were included in the meta-analysis. Fluid overload and cumulative fluid balance were both associated with pooled mortality: after 3 days of ICU stay, adjusted relative risk for fluid overload was 8.83 (95% CI, 4.03-19.33), and for cumulative fluid balance 2.15 (95% CI, 1.51-3.07), at any time point, adjusted relative risk for fluid overload was 2.79 (95% CI, 1.55-5.00) and 1.39 (95% CI, 1.15-1.69) for cumulative fluid balance. Fluid overload was associated with mortality in patients with both acute kidney injury (adjusted relative risk, 2.38; 95% CI, 1.75-2.98) and surgery (adjusted relative risk, 6.17; 95% CI, 4.81-7.97). Cumulative fluid balance was linked to mortality in patients with sepsis (adjusted relative risk, 1.66; 95% CI, 1.39-1.98), acute kidney injury (adjusted relative risk, 2.63; 95% CI, 1.30-5.30), and respiratory failure (adjusted relative risk, 1.19; 95% CI, 1.03-1.43). The risk of mortality increased by a factor of 1.19 (95% CI, 1.11-1.28) per liter increase in positive fluid balance. CONCLUSIONS This systematic review and meta-analysis of observational studies reporting adjusted risk estimates suggests that fluid overload and positive cumulative fluid balance are associated with increased mortality in a general population and defined subgroups of critically ill patients.

Timing of Intubation and Mortality Among Critically Ill Coronavirus Disease 2019 Patients: A Single-Center Cohort Study.

Abstract: Objectives Increasing time to mechanical ventilation and high-flow nasal cannula use may be associated with mortality in coronavirus disease 2019. We examined the impact of time to intubation and use of high-flow nasal cannula on clinical outcomes in patients with coronavirus disease 2019. Design Retrospective cohort study. Setting Six coronavirus disease 2019-specific ICUs across four university-affiliated hospitals in Atlanta, Georgia. Patients Adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection who received high-flow nasal cannula or mechanical ventilation. Interventions None. Measurements and main results Among 231 patients admitted to the ICU, 109 (47.2%) were treated with high-flow nasal cannula and 97 (42.0%) were intubated without preceding high-flow nasal cannula use. Of those managed with high-flow nasal cannula, 78 (71.6%) ultimately received mechanical ventilation. In total, 175 patients received mechanical ventilation; 44.6% were female, 66.3% were Black, and the median age was 66 years (interquartile range, 56-75 yr). Seventy-six patients (43.4%) were intubated within 8 hours of ICU admission, 57 (32.6%) between 8 and 24 hours of admission, and 42 (24.0%) greater than or equal to 24 hours after admission. Patients intubated within 8 hours were more likely to have diabetes, chronic comorbidities, and higher admission Sequential Organ Failure Assessment scores. Mortality did not differ by time to intubation (≤ 8 hr: 38.2%; 8-24 hr: 31.6%; ≥ 24 hr: 38.1%; p = 0.7), and there was no association between time to intubation and mortality in adjusted analysis. Similarly, there was no difference in initial static compliance, duration of mechanical ventilation, or ICU length of stay by timing of intubation. High-flow nasal cannula use prior to intubation was not associated with mortality. Conclusions In this cohort of critically ill patients with coronavirus disease 2019, neither time from ICU admission to intubation nor high-flow nasal cannula use were associated with increased mortality. This study provides evidence that coronavirus disease 2019 respiratory failure can be managed similarly to hypoxic respiratory failure of other etiologies.

Adult ICU Triage During the Coronavirus Disease 2019 Pandemic: Who Will Live and Who Will Die? Recommendations to Improve Survival.

Abstract: OBJECTIVES: Coronavirus disease 2019 patients are currently overwhelming the world's healthcare systems. This article provides practical guidance to front-line physicians forced to make critical rationing decisions. DATA SOURCES: PubMed and Medline search for scientific literature, reviews, and guidance documents related to epidemic ICU triage including from professional bodies. STUDY SELECTION: Clinical studies, reviews, and guidelines were selected and reviewed by all authors and discussed by internet conference and email. DATA EXTRACTION: References and data were based on relevance and author consensus. DATA SYNTHESIS: We review key challenges of resource-driven triage and data from affected ICUs. We recommend that once available resources are maximally extended, triage is justified utilizing a strategy that provides the greatest good for the greatest number of patients. A triage algorithm based on clinical estimations of the incremental survival benefit (saving the most life-years) provided by ICU care is proposed. "First come, first served" is used to choose between individuals with equal priorities and benefits. The algorithm provides practical guidance, is easy to follow, rapidly implementable and flexible. It has four prioritization categories: performance score, ASA score, number of organ failures, and predicted survival. Individual units can readily adapt the algorithm to meet local requirements for the evolving pandemic. Although the algorithm improves consistency and provides practical and psychologic support to those performing triage, the final decision remains a clinical one. Depending on country and operational circumstances, triage decisions may be made by a triage team or individual doctors. However, an experienced critical care specialist physician should be ultimately responsible for the triage decision. Cautious discharge criteria are proposed acknowledging the difficulties to facilitate the admission of queuing patients. CONCLUSIONS: Individual institutions may use this guidance to develop prospective protocols that assist the implementation of triage decisions to ensure fairness, enhance consistency, and decrease provider moral distress.

Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019-Induced Acute Respiratory Distress Syndrome: A Multicenter Descriptive Study.

Abstract: OBJECTIVES: Severe acute respiratory distress syndrome is complicated with coronavirus disease 2019 and extracorporeal membrane oxygenation support may be necessary in severe cases. This study is to summarize the clinical features, extracorporeal membrane oxygenation characteristics, and outcomes of patients with severe acute respiratory syndrome coronavirus 2 pneumonia received extracorporeal membrane oxygenation. DESIGN: Descriptive study from two hospitals. SETTING: The ICUs from university hospitals. PATIENTS: Patients with severe acute respiratory syndrome coronavirus 2 pneumonia received mechanical ventilation, including those underwent extracorporeal membrane oxygenation from Zhongnan Hospital of Wuhan University and Wuhan Pulmonary Hospital from January 8, 2020, to March 31, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical records, laboratory results, ventilator parameters, and extracorporeal membrane oxygenation-related data were abstracted from the medical records. One-hundred twenty-nine critically ill patients with severe acute respiratory syndrome coronavirus 2 pneumonia were admitted to ICU of the two referral hospitals. Fifty-nine patients received mechanical ventilation and 21 of them received extracorporeal membrane oxygenation support (fourteen from Zhongnan hospital and seven from Wuhan pulmonary hospital). Compared to mechanical ventilation patients without extracorporeal membrane oxygenation support, there was a tendency of decline in mortality but with no significant difference (no-extracorporeal membrane oxygenation group 24/38 [63.2%] vs extracorporeal membrane oxygenation group 12/21 [57.1%]; p = 0.782). For those patients with extracorporeal membrane oxygenation, 12 patients died and nine survived by April 7, 2020. Among extracorporeal membrane oxygenation patients, the PaCO2 prior to extracorporeal membrane oxygenation was lower (54.40 mm Hg [29.20-57.50 mm Hg] vs 63.20 mm Hg [55.40-72.12 mm Hg]; p = 0.006), and pH prior to extracorporeal membrane oxygenation was higher (7.38 [7.28-7.48] vs 7.23 [7.16-7.33]; p = 0.023) in survivors than nonsurvivors. CONCLUSIONS: Extracorporeal membrane oxygenation might be an effective salvage treatment for patients with severe acute respiratory syndrome coronavirus 2 pneumonia associated with severe acute respiratory distress syndrome. Severe CO2 retention and acidosis prior to extracorporeal membrane oxygenation indicated a poor prognosis.

Key Takeaways From the U.S. CDC's 2019 Antibiotic Resistance Threats Report for Frontline Providers.

Abstract: Critical Care Medicine www.ccmjournal.org 1 Critical care and other acute care providers on the frontline are no strangers to the problem of antibiotic resistance (AR). They strive daily at the bedside to predict the presence of resistant pathogens and preempt their detrimental effects in a highly vulnerable host population. However, what appears to represent frontline combat is in fact a complex interaction between the healthcare provider and their microadversaries with downstream implications that go far beyond the bedside and involve the local surroundings as well as the population at large. This cross-dimensional connectivity is probably best understood by conceptualizing the different milieux as concentric spheres (Fig. 1). The inner sphere represents a microcosm that encases the provider, the patient, and the pathogen. Here, management decisions prioritize improving patients’ outcomes and protecting them from acquiring resistant pathogens. The middle sphere pertains to the care setting and immediate surroundings. Here, institutional memory, guidelines, formularies, antibiograms, and feedback from antibiotic stewards inform providers’ predictions of resistance and selection of empiric therapy. The burden of resistance in the middle sphere is closely tied to provider behaviors around hand hygiene, isolation, decolonization, barrier protections, and procedural checklists. The outermost sphere pertains to the larger regional, national, or global environments. Indeed, this sphere is generally of lesser immediate relevance to the outcome of a severely ill patient. It is impacted by multiple external factors not limited to antibiotic overuse in food animals, agricultural contamination, international travel, and national and global policies as well as potential secondary infections and healthcare system collapses during viral pandemics such as coronavirus disease 2019. Busy clinicians siloed within their care settings often tend to place this outer sphere on the backburner. However, in reality, these arbitrary spheres are rather fluid and an action in one can have far-reaching consequences in the other. Despite multiple, well-recognized drivers for the development of resistance (1), indiscriminate antibiotic prescribing in the inner sphere is undoubtedly the most important driver that has catapulted the resistance problem into the daunting global crisis as we know it today. By sheer virtue of the environments they work in and the populations they serve, the community of critical care and other frontline providers has the power and potential to tip the resistance scale in either direction even on a population scale. A paradigm change is in order. Providers must assume a greater stake in the greater good, i.e. curbing the resistance crisis. Maintaining a tighter grasp on the ever-changing epidemiology of resistance will enable them to frequently appraise their own practices in light of population-based observations. The U.S. Centers for Disease Control and Prevention (CDC) recently released the 2019 AR Threats Report (2), a 140-page public document that provides an eye-catching landscape of the current state of the resistance crisis in the United States. This represents a tremendous body of work that was put together by a team of CDC scientists and a few external collaborators with collective expertise in infectious diseases, microbiology, epidemiology, data science, and policy. This is the second U.S. AR threats report of its kind. The previous report (3) from 2013 was based primarily on a point-prevalence survey and was thought to potentially underestimate the burden of deaths (4). The new 2019 report represents a major step forward; in addition to surveillance data, it leverages electronic health record and administrative data and relies on an American Hospital Association–weighted extrapolation to obtain national estimates. Importantly, this is an invaluable resource for critical care providers interested in obtaining a 30,000-foot view of the AR crisis in the United States—an account of that “outer sphere.” In the 2019 CDC report, comparisons of pathogen-specific prevalence in the 2019 report are generally reported for 2012/2013 versus 2017 using data from same source for both periods. The full report (2) is certainly worth a read. Below are some highlights from the report that focus on resistance phenotypes likely to be encountered in the critical care and other acute The opinions expressed in this article are those of the author and do not represent any position or policy of the National Institutes of Health, the U.S. Department of Health and Human Services, or the U.S. government. Supported, in part, by the intramural research program of the National Institutes of Health Clinical Center. Dr. Kadri received support for article research from the National Institutes of Health, and he disclosed government work. Key Takeaways From the U.S. CDC’s 2019 Antibiotic Resistance Threats Report for Frontline Providers

Trajectory of Mortality and Health-Related Quality of Life Morbidity Following Community-Acquired Pediatric Septic Shock.

Abstract: Objectives In-hospital pediatric sepsis mortality has decreased substantially, but long-term mortality and morbidity among children initially surviving sepsis, is unknown. Accordingly, the Life After Pediatric Sepsis Evaluation investigation was conducted to describe the trajectory of mortality and health-related quality of life morbidity for children encountering community-acquired septic shock. Design Prospective, cohort-outcome study, conducted 2013-2017. Setting Twelve academic PICUs in the United States. Patients Critically ill children, 1 month to 18 years, with community-acquired septic shock requiring vasoactive-inotropic support. Interventions Demographic, infection, illness severity, organ dysfunction, and resource utilization data were collected daily during PICU admission. Serial parent proxy-report health-related quality of life assessments were obtained at baseline, 7 days, and 1, 3, 6, and 12 months following PICU admission utilizing the Pediatric Quality of Life Inventory or Stein-Jessop Functional Status Scale. Measurements and main results Among 389 children enrolled, mean age was 7.4 ± 5.8 years; 46% were female; 18% were immunocompromised; and 51% demonstrated chronic comorbidities. Baseline Pediatric Overall Performance Category was normal in 38%. Median (Q1-Q3) Pediatric Risk of Mortality and Pediatric Logistic Organ Dysfunction scores at PICU admission were 11.0 (6.0-17.0) and 9.0 (6.0-11.0); durations of vasoactive-inotropic and mechanical ventilation support were 3.0 days (2.0-6.0 d) and 8.0 days (5.0-14.0 d); and durations of PICU and hospital stay were 9.4 days (5.6-15.4 d) and 15.7 days (9.2-26.0 d). At 1, 3, 6, and 12 months following PICU admission for the septic shock event, 8%, 11%, 12%, and 13% of patients had died, while 50%, 37%, 30%, and 35% of surviving patients had not regained their baseline health-related quality of life. Conclusions This investigation provides the first longitudinal description of long-term mortality and clinically relevant, health-related quality of life morbidity among children encountering community-acquired septic shock. Although in-hospital mortality was 9%, 35% of survivors demonstrated significant, health-related quality of life deterioration from baseline that persisted at least 1 year following hospitalization for septic shock.

Mesenchymal Stem Cell-Derived Extracellular Vesicles Alleviate Acute Lung Injury Via Transfer of miR-27a-3p.

Abstract: Objectives The goal of this study was to determine the role of microRNA transfer in mediating the effects of mesenchymal stem cell-derived extracellular vesicles in acute lung injury. Design Experimental cell and animal studies. Setting University-based research laboratory. Subjects THP-1 monocytes, bone marrow-derived macrophages, and C57BL/6 mice. Interventions To determine the microRNA transfer in vitro, mesenchymal stem cells and mesenchymal stem cell-derived extracellular vesicles were cultured with THP-1 cells and bone marrow-derived macrophages and then assayed for microRNA expression in the target cells. To examine the role of microRNA transfer in vivo, mesenchymal stem cell-derived extracellular vesicles were administered to mice with lipopolysaccharide-induced lung injury. Measurements and main results Mesenchymal stem cell-derived extracellular vesicles were efficiently taken up by macrophages in vitro and in vivo. miR-27a-3p was one of the most highly expressed microRNAs in THP-1 cells in microarray analysis and was transferred from mesenchymal stem cells and mesenchymal stem cell-derived extracellular vesicles to THP-1/bone marrow-derived macrophages. Mesenchymal stem cell-derived extracellular vesicles promoted M2 polarization in bone marrow-derived macrophages, which was inhibited by lentiviral anti-miR-27a-3p transduction. Mesenchymal stem cell-derived extracellular vesicles administered systemically and intratracheally were as effective as mesenchymal stem cells in alleviating acute lung injury, elevating miR-27a-3p levels in alveolar macrophages, and promoting M2 macrophage polarization. Treatment of mesenchymal stem cell-derived extracellular vesicles concurrently decreased alveolar macrophage expression of nuclear factor kappa B subunit 1, a target of miR-27a-3p. Lentiviral transduction of mesenchymal stem cells with anti-miR-27a-3p or knockdown of miR-27a-3p in vivo abolished the effects of mesenchymal stem cell-derived extracellular vesicles on acute lung injury and M2 macrophage polarization. Conclusions Mesenchymal stem cell-derived extracellular vesicles mitigate acute lung injury at least partially via transferring miR-27a-3p to alveolar macrophages. miR-27a-3p acts to target NFKB1 and is a crucial regulator of M2 macrophage polarization.

Association Between Cardiac Injury and Mortality in Hospitalized Patients Infected With Avian Influenza A (H7N9) Virus.

Abstract: OBJECTIVES To evaluate the prevalence of cardiac injury and its association with mortality in hospitalized patients infected with avian influenza A (H7N9) virus. DESIGN Retrospective cohort study. SETTING A total of 133 hospitals in 17 provinces, autonomous regions, and municipalities of mainland China that admitted influenza A (H7N9) virus-infected patients between January 22, 2015, and June 16, 2017. PATIENTS A total of 321 patients with influenza A (H7N9) virus infection were included in the final analysis. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Demographics and clinical characteristics were collected from medical records. Cardiac injury was defined according to cardiac biomarkers, electrocardiography, or echocardiography. Among the 321 patients, 203 (63.2%) showed evidence of cardiac injury. Compared with the uninjured group, the cardiac injury group had lower PaO2/FIO2 (median, 102.0 vs 148.4 mm Hg; p < 0.001), higher Acute Physiology and Chronic Health Evaluation II score (median, 17.0 vs 11.0; p < 0.001), longer stay in the ICU (10.0 vs 9.0 d; p = 0.029), and higher proportion of in-hospital death (64.0% vs 20.3%; p < 0.001). The proportion of virus clearance until discharge or death was lower in the cardiac injury group than in the uninjured group (58.6% vs 86.4%; p < 0.001). Multivariable-adjusted Cox proportional hazards regression analysis showed that cardiac injury was associated with higher mortality (hazards ratio, 2.06; 95% CI, 1.31-3.24) during hospitalization. CONCLUSIONS Cardiac injury is a frequent condition among hospitalized patients infected with influenza A (H7N9) virus, and it is associated with higher risk of mortality.

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Cardiovascular, Endocrine, Hematologic, Pulmonary, and Renal Considerations.

Abstract: Objectives To develop evidence-based recommendations for clinicians caring for adults with acute or acute on chronic liver failure in the ICU. Design The guideline panel comprised 29 members with expertise in aspects of care of the critically ill patient with liver failure and/or methodology. The Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy were followed throughout. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. Setting The panel was divided into nine subgroups: cardiovascular, hematology, pulmonary, renal, endocrine and nutrition, gastrointestinal, infection, perioperative, and neurology. Interventions We developed and selected population, intervention, comparison, and outcomes questions according to importance to patients and practicing clinicians. For each population, intervention, comparison, and outcomes question, we conducted a systematic review aiming to identify the best available evidence, statistically summarized the evidence whenever applicable, and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. Measurements and main results In this article, we report 29 recommendations (from 30 population, intervention, comparison, and outcomes questions) on the management acute or acute on chronic liver failure in the ICU, related to five groups (cardiovascular, hematology, pulmonary, renal, and endocrine). Overall, six were strong recommendations, 19 were conditional recommendations, four were best-practice statements, and in two instances, the panel did not issue a recommendation due to insufficient evidence. Conclusions Multidisciplinary international experts were able to formulate evidence-based recommendations for the management acute or acute on chronic liver failure in the ICU, acknowledging that most recommendations were based on low-quality indirect evidence.

Thromboelastography Profiles of Critically Ill Patients With Coronavirus Disease 2019.

Abstract: Objectives The rate of thromboembolic events among patients with coronavirus disease 2019 is high; however, there is no robust method to identify those at greatest risk We reviewed thromboelastography studies in critically ill patients with coronavirus disease 2019 to characterize their coagulation states Design Retrospective Setting Tertiary ICU in New York City Patients Sixty-four patients with coronavirus disease 2019 admitted to the ICU with thromboelastography performed Interventions None Measurements and main results Fifty percent of patients had a clotting index in the hypercoagulable range (clotting index > 3) (median 305) Reaction time and K values were below the lower limit of normal in 438% of the population consistent with a hypercoagulable profile The median α angle and maximum amplitude (758° and 728 mm, respectively) were in the hypercoagulable range The α angle was above reference range in 703% of patients indicative of rapid clot formation Maximum amplitude, a factor of fibrinogen and platelet count and function, and a measure of clot strength was above reference range in 601% of patients Thirty-one percent had thromboembolic events; thromboelastography parameters did not correlate with events in our cohort Those with D-dimer values greater than 2,000 were more likely to have shorter reaction times compared with those with D-dimer levels less than or equal to 2,000 (48 vs 56 min; p = 0001) Conclusions A large proportion of critically ill patients with coronavirus disease 2019 have hypercoagulable thromboelastography profiles with additional derangements related to fibrinogen and platelet function As the majority of patients have an elevated thromboelastography maximum amplitude, a follow-up study evaluating platelet aggregation would be instructive

Boarding of Critically Ill Patients in the Emergency Department.

Abstract: OBJECTIVES Emergency department boarding is the practice of caring for admitted patients in the emergency department after hospital admission, and boarding has been a growing problem in the United States. Boarding of the critically ill has achieved specific attention because of its association with poor clinical outcomes. Accordingly, the Society of Critical Care Medicine and the American College of Emergency Physicians convened a Task Force to understand the implications of emergency department boarding of the critically ill. The objective of this article is to review the U.S. literature on (1) the frequency of emergency department boarding among the critically ill, (2) the outcomes associated with critical care patient boarding, and (3) local strategies developed to mitigate the impact of emergency department critical care boarding on patient outcomes. DATA SOURCES AND STUDY SELECTION Review article. DATA EXTRACTION AND DATA SYNTHESIS Emergency department-based boarding of the critically ill patient is common, but no nationally representative frequency estimates has been reported. Boarding literature is limited by variation in the definitions used for boarding and variation in the facilities studied (boarding ranges from 2% to 88% of ICU admissions). Prolonged boarding in the emergency department has been associated with longer duration of mechanical ventilation, longer ICU and hospital length of stay, and higher mortality. Health systems have developed multiple mitigation strategies to address emergency department boarding of critically ill patients, including emergency department-based interventions, hospital-based interventions, and emergency department-based resuscitation care units. CONCLUSIONS Emergency department boarding of critically ill patients was common and was associated with worse clinical outcomes. Health systems have generated a number of strategies to mitigate these effects. A definition for emergency department boarding is proposed. Future work should establish formal criteria for analysis and benchmarking of emergency department-based boarding overall, with subsequent efforts focused on developing and reporting innovative strategies that improve clinical outcomes of critically ill patients boarded in the emergency department.

Sepsis and Coronavirus Disease 2019: Common Features and Anti-Inflammatory Therapeutic Approaches

Abstract: Great efforts are being made worldwide to identify the specific clinical characteristics of infected critically ill patients that mediate the associated pathogenesis, including vascular dysfunction, thrombosis, dysregulated inflammation, and respiratory complications. Recently, coronavirus disease 2019 has been closely related to sepsis, which suggests that most deaths in ICUs in infected patients are produced by viral sepsis. Understanding the physiopathology of the disease that lead to sepsis after severe acute respiratory syndrome coronavirus 2 infection is a current clinical need to improve intensive care-applied therapies applied to critically ill patients. Although the whole representative data characterizing the immune and inflammatory status in coronavirus disease 2019 patients are not completely known, it is clear that hyperinflammation and coagulopathy contribute to disease severity. Here, we present some common features shared by severe coronavirus disease 2019 patients and sepsis and describe proposed anti-inflammatory therapies for coronavirus disease 2019 which have been previously evaluated in sepsis.

Critical Illness Factors Associated With Long-Term Mortality and Health-Related Quality of Life Morbidity Following Community-Acquired Pediatric Septic Shock.

Abstract: OBJECTIVES A companion article reports the trajectory of long-term mortality and significant health-related quality of life disability among children encountering septic shock. In this article, the investigators examine critical illness factors associated with these adverse outcomes. DESIGN Prospective, cohort-outcome study, conducted 2013-2017. SETTING Twelve United States academic PICUs. PATIENTS Critically ill children, 1 month to 18 years, with community-acquired septic shock requiring vasoactive-inotropic support. INTERVENTIONS Illness severity, organ dysfunction, and resource utilization data were collected during PICU admission. Change from baseline health-related quality of life at the month 3 follow-up was assessed by parent proxy-report employing the Pediatric Quality of Life Inventory or the Stein-Jessop Functional Status Scale. MEASUREMENTS AND MAIN RESULTS In univariable modeling, critical illness variables associated with death and/or persistent, serious health-related quality of life deterioration were candidates for multivariable modeling using Bayesian information criterion. The most clinically relevant multivariable models were selected among models with near-optimal statistical fit. Three months following septic shock, 346 of 389 subjects (88.9%) were alive and 43 of 389 had died (11.1%); 203 of 389 (52.2%) had completed paired health-related quality of life surveys. Pediatric Risk of Mortality, cumulative Pediatric Logistic Organ Dysfunction scores, PICU and hospital durations of stay, maximum and cumulative vasoactive-inotropic scores, duration of mechanical ventilation, need for renal replacement therapy, extracorporeal life support or cardiopulmonary resuscitation, and appearance of pathologic neurologic signs were associated with adverse outcomes in univariable models. In multivariable regression analysis (odds ratio [95% CI]), summation of daily Pediatric Logistic Organ Dysfunction scores, 1.01/per point (1.01-1.02), p < 0.001; highest vasoactive-inotropic score, 1.02/per point (1.00-1.04), p = 0.003; and any acute pathologic neurologic sign/event, 5.04 (2.15-12.01), p < 0.001 were independently associated with death or persistent, serious deterioration of health-related quality of life at month 3. CONCLUSIONS AND RELEVANCE Biologically plausible factors related to sepsis-associated critical illness organ dysfunction and its treatment were associated with poor outcomes at month 3 follow-up among children encountering septic shock.

Prevalence and Impact of Hyponatremia in Patients With Coronavirus Disease 2019 in New York City

Abstract: Objectives Hyponatremia occurs in up to 30% of patients with pneumonia and is associated with increased morbidity and mortality. The prevalence of hyponatremia associated with coronavirus disease 2019 and the impact on outcome is unknown. We aimed to identify the prevalence, predictors, and impact on outcome of mild, moderate, and severe admission hyponatremia compared with normonatremia among coronavirus disease 2019 patients. Design Retrospective, multicenter, observational cohort study. Setting Four New York City hospitals that are part of the same health network. Patients Hospitalized, laboratory-confirmed adult coronavirus disease 2019 patients admitted between March 1, 2020, and May 13, 2020. Interventions None. Measurements and main results Hyponatremia was categorized as mild (sodium: 130-134 mmol/L), moderate (sodium: 121-129 mmol/L), or severe (sodium: ≤ 120 mmol/L) versus normonatremia (135-145 mmol/L). The primary outcome was the association of increasing severity of hyponatremia and in-hospital mortality assessed using multivariable logistic regression analysis. Secondary outcomes included encephalopathy, acute renal failure, mechanical ventilation, and discharge home compared across sodium levels using Kruskal-Wallis and chi-square tests. In exploratory analysis, the association of sodium levels and interleukin-6 levels (which has been linked to nonosmotic release of vasopressin) was assessed. Among 4,645 patient encounters, hyponatremia (sodium Conclusions Hyponatremia occurred in nearly a third of coronavirus disease 2019 patients, was an independent predictor of in-hospital mortality, and was associated with increased risk of encephalopathy and mechanical ventilation.

Comparative Performance of Pulmonary Ultrasound, Chest Radiograph, and CT Among Patients With Acute Respiratory Failure.

Abstract: OBJECTIVES The study goal was to concurrently evaluate agreement of a 9-point pulmonary ultrasound protocol and portable chest radiograph with chest CT for localization of pathology to the correct lung and also to specific anatomic lobes among a diverse group of intubated patients with acute respiratory failure. DESIGN Prospective cohort study. SETTING Medical, surgical, and neurologic ICUs at a 670-bed urban teaching hospital. PATIENTS Intubated adults with acute respiratory failure having chest CT and portable chest radiograph performed within 24 hours of intubation. INTERVENTIONS A 9-point pulmonary ultrasound examination performed at the time of intubation. MEASUREMENTS AND MAIN RESULTS Sixty-seven patients had pulmonary ultrasound, portable chest radiograph, and chest CT performed within 24 hours of intubation. Overall agreement of pulmonary ultrasound and portable chest radiograph findings with correlating lobe ("lobe-specific" agreement) on CT was 87% versus 62% (p < 0.001), respectively. Relaxing the agreement definition to a matching CT finding being present anywhere within the correct lung ("lung-specific" agreement), not necessarily the specific mapped lobe, showed improved agreement for both pulmonary ultrasound and portable chest radiograph respectively (right lung: 92.5% vs 65.7%; p < 0.001 and left lung: 83.6% vs 71.6%; p = 0.097). The highest lobe-specific agreement was for the finding of atelectasis/consolidation for both pulmonary ultrasound and portable chest radiograph (96% and 73%, respectively). The lowest lobe-specific agreement for pulmonary ultrasound was normal lung (79%) and interstitial process for portable chest radiograph (29%). Lobe-specific agreement differed most between pulmonary ultrasound and portable chest radiograph for interstitial findings (86% vs 29%, respectively). Pulmonary ultrasound had the lowest agreement with CT for findings in the left lower lobe (82.1%). Pleural effusion agreement also differed between pulmonary ultrasound and portable chest radiograph (right: 99% vs 87%; p = 0.009 and left: 99% vs 85%; p = 0.004). CONCLUSIONS A clinical, 9-point pulmonary ultrasound protocol strongly agreed with specific CT findings when analyzed by both lung- and lobe-specific location among a diverse population of mechanically ventilated patients with acute respiratory failure; in this regard, pulmonary ultrasound significantly outperformed portable chest radiograph.