Surge Capacity in the COVID-19 Era: a Natural Experiment of Neurocritical Care in General Critical Care.

BACKGROUND: COVID-19 surges led to significant challenges in ensuring critical care capacity. In response, some centers leveraged neurocritical care (NCC) capacity as part of the surge response, with neurointensivists providing general critical care for patients with COVID-19 without neurologic illness. The relative outcomes of NCC critical care management of patients with COVID-19 remain unclear and may help guide further surge planning and provide broader insights into general critical care provided in NCC units. METHODS: We performed an observational cohort study of all patients requiring critical care for COVID-19 across four hospitals within the Emory Healthcare system during the first three surges. Patients were categorized on the basis of admission to intensive care units (ICUs) staffed by general intensivists or neurointensivists. Patients with primary neurological diagnoses were excluded. Baseline demographics, clinical complications, and outcomes were compared between groups using univariable and propensity score matching statistics. RESULTS: A total of 1141 patients with a primary diagnosis of COVID-19 required ICU admission. ICUs were staffed by general intensivists (n = 1071) or neurointensivists (n = 70). Baseline demographics and presentation characteristics were similar between groups, except for patients admitted to neurointensivist-staffed ICUs being younger (59 vs. 65, p = 0.027) and having a higher PaO2/FiO2 ratio (153 vs. 120, p = 0.002). After propensity score matching, there was no correlation between ICU staffing and the use of mechanical ventilation, renal replacement therapy, and vasopressors. The rates of in-hospital mortality and hospice disposition were similar in neurointensivist-staffed COVID-19 units (odds ratio 0.9, 95% confidence interval 0.31-2.64, p = 0.842). CONCLUSIONS: COVID-19 surges precipitated a natural experiment in which neurology-trained neurointensivists provided critical care in a comparable context to general intensivists treating the same disease. Neurology-trained neurointensivists delivered comparable outcomes to those of general ICUs during COVID-19 surges. These results further support the role of NCC in meeting general critical care needs of neurocritically ill patients and as a viable surge resource in general critical care.

Coronavirus Disease 2019 Temperature Trajectories Correlate With Hyperinflammatory and Hypercoagulable Subphenotypes.

OBJECTIVES: Body temperature trajectories of infected patients are associated with specific immune profiles and survival. We determined the association between temperature trajectories and distinct manifestations of coronavirus disease 2019. DESIGN: Retrospective observational study. SETTING: Four hospitals within an academic healthcare system from March 2020 to February 2021. PATIENTS: All adult patients hospitalized with coronavirus disease 2019. INTERVENTIONS: Using a validated group-based trajectory model, we classified patients into four previously defined temperature trajectory subphenotypes using oral temperature measurements from the first 72 hours of hospitalization. Clinical characteristics, biomarkers, and outcomes were compared between subphenotypes. MEASUREMENTS AND MAIN RESULTS: The 5,903 hospitalized coronavirus disease 2019 patients were classified into four subphenotypes: hyperthermic slow resolvers (n = 1,452, 25%), hyperthermic fast resolvers (1,469, 25%), normothermics (2,126, 36%), and hypothermics (856, 15%). Hypothermics had abnormal coagulation markers, with the highest d-dimer and fibrin monomers (p < 0.001) and the highest prevalence of cerebrovascular accidents (10%, p = 0.001). The prevalence of venous thromboembolism was significantly different between subphenotypes (p = 0.005), with the highest rate in hypothermics (8.5%) and lowest in hyperthermic slow resolvers (5.1%). Hyperthermic slow resolvers had abnormal inflammatory markers, with the highest C-reactive protein, ferritin, and interleukin-6 (p < 0.001). Hyperthermic slow resolvers had increased odds of mechanical ventilation, vasopressors, and 30-day inpatient mortality (odds ratio, 1.58; 95% CI, 1.13-2.19) compared with hyperthermic fast resolvers. Over the course of the pandemic, we observed a drastic decrease in the prevalence of hyperthermic slow resolvers, from representing 53% of admissions in March 2020 to less than 15% by 2021. We found that dexamethasone use was associated with significant reduction in probability of hyperthermic slow resolvers membership (27% reduction; 95% CI, 23-31%; p < 0.001). CONCLUSIONS: Hypothermics had abnormal coagulation markers, suggesting a hypercoagulable subphenotype. Hyperthermic slow resolvers had elevated inflammatory markers and the highest odds of mortality, suggesting a hyperinflammatory subphenotype. Future work should investigate whether temperature subphenotypes benefit from targeted antithrombotic and anti-inflammatory strategies.

Trends in ICU Mortality From Coronavirus Disease 2019: A Tale of Three Surges.

OBJECTIVES: To determine the association between time period of hospitalization and hospital mortality among critically ill adults with coronavirus disease 2019. DESIGN: Observational cohort study from March 6, 2020, to January 31, 2021. SETTING: ICUs at four hospitals within an academic health center network in Atlanta, GA. PATIENTS: Adults greater than or equal to 18 years with coronavirus disease 2019 admitted to an ICU during the study period (i.e., Surge 1: March to April, Lull 1: May to June, Surge 2: July to August, Lull 2: September to November, Surge 3: December to January). MEASUREMENTS AND MAIN RESULTS: Among 1,686 patients with coronavirus disease 2019 admitted to an ICU during the study period, all-cause hospital mortality was 29.7%. Mortality differed significantly over time: 28.7% in Surge 1, 21.3% in Lull 1, 25.2% in Surge 2, 30.2% in Lull 2, 34.7% in Surge 3 (p = 0.007). Mortality was significantly associated with 1) preexisting risk factors (older age, race, ethnicity, lower body mass index, higher Elixhauser Comorbidity Index, admission from a nursing home); 2) clinical status at ICU admission (higher Sequential Organ Failure Assessment score, higher d-dimer, higher C-reactive protein); and 3) ICU interventions (receipt of mechanical ventilation, vasopressors, renal replacement therapy, inhaled vasodilators). After adjusting for baseline and clinical variables, there was a significantly increased risk of mortality associated with admission during Lull 2 (relative risk, 1.37 [95% CI = 1.03-1.81]) and Surge 3 (relative risk, 1.35 [95% CI = 1.04-1.77]) as compared to Surge 1. CONCLUSIONS: Despite increased experience and evidence-based treatments, the risk of death for patients admitted to the ICU with coronavirus disease 2019 was highest during the fall and winter of 2020. Reasons for this increased mortality are not clear.

Critical Care Response During the COVID-19 Pandemic.

Hospitals and health care systems with active critical care organizations (CCOs) that unified ICU units before the onset of the COVID-19 Pandemic were better positioned to adapt to the demands of the pandemic, due to their established standardization of care and integration of critical care within the larger structure of the hospital or health care system. CCOs should continue to make changes, based on the real experience of COVID-19 that would lead to improved care during the ongoing pandemic, and beyond.

Altered Heart Rate Variability Early in ICU Admission Differentiates Critically Ill Coronavirus Disease 2019 and All-Cause Sepsis Patients.

IMPORTANCE: Altered heart rate variability has been associated with autonomic dysfunction in a number of disease profiles, in this work we elucidate differences in the biomarker among patients with all-cause sepsis and coronavirus disease 2019. OBJECTIVES: To measure heart rate variability metrics in critically ill coronavirus disease 2019 patients with comparison to all-cause critically ill sepsis patients. DESIGN SETTING AND PARTICIPANTS: Retrospective analysis of coronavirus disease 2019 patients admitted to an ICU for at least 24 hours at any of Emory Healthcare ICUs between March 2020 and April 2020 up to 5 days of ICU stay. The comparison group was a cohort of all-cause sepsis patients prior to coronavirus disease 2019 pandemic. MAIN OUTCOMES AND MEASURES: Continuous waveforms were captured from the patient monitor. The electrocardiogram was then analyzed for each patient over a 300 seconds observational window that was shifted by 30 seconds in each iteration from admission till discharge. A total of 23 heart rate variability metrics were extracted in each iteration. We use the Kruskal-Wallis and Steel-Dwass tests (p < 0.05) for statistical analysis and interpretations of heart rate variability multiple measures. RESULTS: A total of 141 critically ill coronavirus disease 2019 patients met inclusion criteria, who were compared with 208 patients with all-cause sepsis. Three nonlinear markers, including the ratio of standard deviation derived from the Poincaré plot, sample entropy, and approximate entropy and four linear features, including mode of beat-to-beat interval, acceleration capacity, deceleration capacity, and the proportion of consecutive RR intervals that differ by more than 50 ms, were all statistically significant (p < 0.05) between the coronavirus disease 2019 and all-cause sepsis cohorts. The three nonlinear features and acceleration capacity, deceleration capacity, and beat-to-beat interval (mode) were statistically significant (p < 0.05) when comparing pairwise analysis among the combinations of survivors and nonsurvivors between the coronavirus disease 2019 and sepsis cohorts. Temporal analysis of the main markers showed low variability across the 5 days of analysis compared with sepsis patients. CONCLUSIONS AND RELEVANCE: In this descriptive statistical study, heart rate variability measures were found to be statistically different across critically ill patients infected with severe acute respiratory syndrome coronavirus 2 and distinct from bacterial sepsis.

Developing Treatment Guidelines During a Pandemic Health Crisis: Lessons Learned From COVID-19.

The development of the National Institutes of Health (NIH) COVID-19 Treatment Guidelines began in March 2020 in response to a request from the White House Coronavirus Task Force. Within 4 days of the request, the NIH COVID-19 Treatment Guidelines Panel was established and the first meeting took place (virtually-as did subsequent meetings). The Panel comprises 57 individuals representing 6 governmental agencies, 11 professional societies, and 33 medical centers, plus 2 community members, who have worked together to create and frequently update the guidelines on the basis of evidence from the most recent clinical studies available. The initial version of the guidelines was completed within 2 weeks and posted online on 21 April 2020. Initially, sparse evidence was available to guide COVID-19 treatment recommendations. However, treatment data rapidly accrued based on results from clinical studies that used various study designs and evaluated different therapeutic agents and approaches. Data have continued to evolve at a rapid pace, leading to 24 revisions and updates of the guidelines in the first year. This process has provided important lessons for responding to an unprecedented public health emergency: Providers and stakeholders are eager to access credible, current treatment guidelines; governmental agencies, professional societies, and health care leaders can work together effectively and expeditiously; panelists from various disciplines, including biostatistics, are important for quickly developing well-informed recommendations; well-powered randomized clinical trials continue to provide the most compelling evidence to guide treatment recommendations; treatment recommendations need to be developed in a confidential setting free from external pressures; development of a user-friendly, web-based format for communicating with health care providers requires substantial administrative support; and frequent updates are necessary as clinical evidence rapidly emerges.

The Coronavirus Disease 2019 Pandemic Impacts Burnout Syndrome Differently Among Multiprofessional Critical Care Clinicians-A Longitudinal Survey Study.

OBJECTIVES: To determine the impact of coronavirus disease 2019 on burnout syndrome in the multiprofessional ICU team and to identify factors associated with burnout syndrome. DESIGN: Longitudinal, cross-sectional survey. SETTING: All adult ICUs within an academic health system. SUBJECTS: Critical care nurses, advanced practice providers, physicians, respiratory therapists, pharmacists, social workers, and spiritual health workers were surveyed on burnout in 2017 and during the coronavirus disease 2019 pandemic in 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Burnout syndrome and contributing factors were measured using the Maslach Burnout Inventory of Health and Human Service and Areas of Worklife Survey. Response rates were 46.5% (572 respondents) in 2017 and 49.9% (710 respondents) in 2020. The prevalence of burnout increased from 59% to 69% (p < 0.001). Nurses were disproportionately impacted, with the highest increase during the pandemic (58-72%; p < 0.0001) with increases in emotional exhaustion and depersonalization, and personal achievement decreases. In contrast, although burnout was high before and during coronavirus disease 2019 in all specialties, most professions had similar or lower burnout in 2020 as they had in 2017. Physicians had the lowest rates of burnout, measured at 51% and 58%, respectively. There was no difference in burnout between clinicians working in ICUs who treated coronavirus disease 2019 than those who did not (71% vs 67%; p = 0.26). Burnout significantly increased in females (71% vs 60%; p = 0.001) and was higher than in males during the pandemic (71% vs 60%; p = 0.01). CONCLUSIONS: Burnout syndrome was common in all multiprofessional ICU team members prior to and increased substantially during the pandemic, independent of whether one treated coronavirus disease 2019 patients. Nurses had the highest prevalence of burnout during coronavirus disease 2019 and had the highest increase in burnout from the prepandemic baseline. Female clinicians were significantly more impacted by burnout than males. Different susceptibility to burnout syndrome may require profession-specific interventions as well as work system improvements.

Integrated evaluation of lung disease in single animals.

During infectious disease, pathogen load drives inflammation and immune response that together contribute to tissue injury often resulting in organ dysfunction. Pulmonary failure in SARS-CoV2-infected hospitalized COVID-19 patients is one such prominent example. Intervention strategies require characterization of the host-pathogen interaction by accurately assessing all of the above-mentioned disease parameters. To study infection in intact mammals, mice are often used as essential genetic models. Due to humane concerns, there is a constant unmet demand to develop studies that reduce the number of mice utilized while generating objective data. Here, we describe an integrated method of evaluating lung inflammation in mice infected with Pseudomonas aeruginosa or murine gammaherpesvirus (MHV)-68. This method conserves animal resources while permitting evaluation of disease mechanisms in both infection settings. Lungs from a single euthanized mouse were used for two purposes-biological assays to determine inflammation and infection load, as well as histology to evaluate tissue architecture. For this concurrent assessment of multiple parameters from a single euthanized mouse, we limit in-situ formalin fixation to the right lung of the cadaver. The unfixed left lung is collected immediately and divided into several segments for biological assays including determination of pathogen titer, assessment of infection-driven cytokine levels and appearance of cell death markers. In situ fixed right lung was then processed for histological determination of tissue injury and confirmation of infection-driven cell death patterns. This method reduces overall animal use and minimizes inter-animal variability that results from sacrificing different animals for different types of assays. The technique can be applied to any lung disease study in mice or other mammals.

The Surviving Sepsis Campaign: Research Priorities for Coronavirus Disease 2019 in Critical Illness.

OBJECTIVES: To identify research priorities in the management, pathophysiology, and host response of coronavirus disease 2019 in critically ill patients. DESIGN: The Surviving Sepsis Research Committee, a multiprofessional group of 17 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine, was virtually convened during the coronavirus disease 2019 pandemic. The committee iteratively developed the recommendations and subsequent document. METHODS: Each committee member submitted a list of what they believed were the most important priorities for coronavirus disease 2019 research. The entire committee voted on 58 submitted questions to determine top priorities for coronavirus disease 2019 research. RESULTS: The Surviving Sepsis Research Committee provides 13 priorities for coronavirus disease 2019. Of these, the top six priorities were identified and include the following questions: 1) Should the approach to ventilator management differ from the standard approach in patients with acute hypoxic respiratory failure?, 2) Can the host response be modulated for therapeutic benefit?, 3) What specific cells are directly targeted by severe acute respiratory syndrome coronavirus 2, and how do these cells respond?, 4) Can early data be used to predict outcomes of coronavirus disease 2019 and, by extension, to guide therapies?, 5) What is the role of prone positioning and noninvasive ventilation in nonventilated patients with coronavirus disease?, and 6) Which interventions are best to use for viral load modulation and when should they be given? CONCLUSIONS: Although knowledge of both biology and treatment has increased exponentially in the first year of the coronavirus disease 2019 pandemic, significant knowledge gaps remain. The research priorities identified represent a roadmap for investigation in coronavirus disease 2019.

Surviving Sepsis Campaign Guidelines on the Management of Adults With Coronavirus Disease 2019 (COVID-19) in the ICU: First Update.

BACKGROUND: The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU. METHODS: The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. RESULTS: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning. CONCLUSION: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.

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

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.