The future of intensive care: the study of the microcirculation will help to guide our therapies.

The goal of hemodynamic resuscitation is to optimize the microcirculation of organs to meet their oxygen and metabolic needs. Clinicians are currently blind to what is happening in the microcirculation of organs, which prevents them from achieving an additional degree of individualization of the hemodynamic resuscitation at tissue level. Indeed, clinicians never know whether optimization of the microcirculation and tissue oxygenation is actually achieved after macrovascular hemodynamic optimization. The challenge for the future is to have noninvasive, easy-to-use equipment that allows reliable assessment and immediate quantitative analysis of the microcirculation at the bedside. There are different methods for assessing the microcirculation at the bedside; all have strengths and challenges. The use of automated analysis and the future possibility of introducing artificial intelligence into analysis software could eliminate observer bias and provide guidance on microvascular-targeted treatment options. In addition, to gain caregiver confidence and support for the need to monitor the microcirculation, it is necessary to demonstrate that incorporating microcirculation analysis into the reasoning guiding hemodynamic resuscitation prevents organ dysfunction and improves the outcome of critically ill patients.

Comparison of Clinical and Thrombotic Outcomes in Sars-Cov-2- Pneumonia Versus Other Viral Pneumonia in an Urban Academic Medical Center

Title: Comparison of Clinical and Thrombotic Outcomes in SARS-CoV-2- Pneumonia versus Other Viral Pneumonia in an Urban Academic Medical Center Objective: To compare clinical and thrombotic outcomes in SARS-CoV-2 pneumonia versus other viral pneumonias. Introduction: Viral pneumonia (PNA) causes oxidative stress to the pulmonary vasculature, triggering endothelial dysfunction and activation of the coagulation cascade. Elevations in coagulation markers, including d-dimer and fibrinogen, have been observed. Recent studies indicate that SARS-CoV-2 infection causes endothelial cell injury, with activation of the coagulation cascade, and a high frequency of systemic thrombotic events. It remains unclear whether it is viral pneumonia itself, a specific viral strain (and/or viral load) that drives the clinical and thrombotic outcomes. Furthermore, limited data is available regarding clinical outcomes in a diverse patient population hospitalized with SARS-CoV-2 infection. This study is from a single urban medical center in Chicago, Illinois. Study Design: A retrospective cohort study evaluating the medical records of hospitalized adult patients admitted to University of Illinois Hospital and Health Sciences System (UIHHSS) with SARS-CoV-2 pneumonia or other viral (H1N1 or H3N2) pneumonia between 10/01/2017 and 09/01/2020. Methods: Patients were included if ≥18 years old, hospitalized, with a primary confirmed diagnosis of viral pneumonia (SARS-CoV-2, H1N1 or H3N2) based on ICD-10 code, viral diagnostic testing, diagnosis description, and appropriate clinical characteristics/imaging studies. Past medical history, inpatient medications, coagulation parameters, arterial/venous thrombotic outcomes, and other clinical outcomes (renal replacement therapy, mechanical ventilation, co-infection) were ed from UIHHSS electronic health record database. Results: Medical records of 257 patient with a primary diagnosis of pneumonia were reviewed, 199 patients with SARS-CoV-2 PNA (95 male, average age 58 years, 52% Hispanic, 37% non-Hispanic Black) and 58 patients with other viral PNA (24 male, average age 63 years, 21% Hispanic, 55% non-Hispanic Black;34 with H3N2, 24 with H1N1). Coagulation parameters (maximum D-dimer, fibrinogen, INR) were similar in both groups;average D-dimer was >3x ULN. Anticoagulation therapy was similarly prescribed in both groups (SARS-CoV-2, 95% vs 84%, H1N1 or H3N2), with prophylactic dose anticoagulation prescribed most frequently (73% vs 62%) and with high average compliance rates (89% vs 83%). Admission to the intensive care unit (ICU;32% vs 29%) and the median length of stay (10 vs 4 days) was similar in both groups. Thrombotic events (n = 6, 3%) occurred only in SARS-CoV-2 PNA patients in the ICU: 3 pulmonary embolism (PE), 1 distal lower extremity deep vein thrombosis (DVT), 2 non-ST elevated myocardial infarctions (NSTEMI). There was a significantly higher incidence of use of renal replacement therapy (8.5% vs 0%, p=0.016) and mortality (15.6% vs 3.4%, p=0.048) in the SARS-CoV-2 PNA group compared to the H3N2/H1N1 PNA group. There were no differences in the rates of mechanical ventilation, the incidence of major bleeding or co-infection. In a multivariable logistic regression analysis, age (aOR 1.07), the presence of SARS-CoV-2 PNA (aOR 11.37), and ICU admission (aOR 41.95) were significantly associated with risk of mortality during hospitalization. Race and ethnicity were not associated with mortality. Conclusion: The overall incidence of thrombotic events was low and occurred only in the SARS-CoV-2 PNA group. The low rate of venous thrombosis detected in this group, especially in the ICU setting, is likely related to the reduced use of diagnostic studies during the first COVID-19 pandemic in 2020 and to the high rates of anticoagulation prophylaxis orders and compliance. SARS-CoV-2 PNA was associated with a higher rate of renal failure and mortality compared to patients with H3N2/H1N1 viral pneumonia. There was no difference in mortality rates between Hispanic and non-Hispanic and between Black and non-Black patients. This study suggests that SARS-CoV-2 pneumonia leads to greater endothelial dysfunction than that observed in H3N2/H1N1 viral pneumonia and that race/ethnicity does not drive mortality outcomes. Disclosures: Benken: BMS: Research Funding;CareDx: Research Funding;Transplant Genomics: Research Funding;Daiichi Sankyo: Research Funding;Verici Dx: Research Funding.

The Association of Altered Mental Status in the Emergency Department With In-Hospital Mortality in COVID-19 Patients

Study Objectives: Altered mental status (AMS) is frequently associated with poor outcomes across a wide spectrum of conditions including infections. This study aims to identify whether AMS in emergency department (ED) patients with COVID-19 is independently associated with in-hospital mortality. Methods: This was a retrospective multicenter cohort study. We included all patients with a positive SARS-CoV-2 PCR within 2 weeks of presentation, who were admitted from the ED of three hospitals in the greater Boston area between March and August 2020. The primary covariate of interest was ED AMS at ED arrival and the primary outcome was in-hospital mortality. The ED charts were abstracted for demographics, comorbid conditions, symptoms, laboratory testing, and radiology testing along with in-hospital outcomes. AMS was defined by documentation of changes in mental status from baseline. We used logistic regression modeling with backwards elimination to determine an adjusted estimate for the independent association of AMS with mortality. Results: We included 824 visits with 51% male, a mean age was 67.1 (SD 17.0) and 153 (18.6%) had AMS. There were 132 deaths for an overall mortality rate of 16.1%. Patients with AMS had in-hospital mortality of 38.2% (95% CI 30.4%-46.4%), compared to 11.1% (8.8%-13.7%) for patients without AMS (p<0.0001). After adjusting for potential confounders, visits by patients with AMS during their stay at the ED had 3.1 (95% CI, 2.1-5.9) times the odds of death compared to those without AMS. Conclusion: Among patients with COVID-19, AMS in the ED was associated with three-fold increase in mortality compared to patients without AMS.

Respiratory disease, and treatment / thematic poster session a novel approach to medical monitoring during the sars-cov-2 pandemic supporting the activ 4b outpatient anticoagulation trial

Rationale The ACTIV 4B (OWS/NHLBI supported) clinical trial addresses the use of anti-platelet and anticoagulant agents in symptomatic COVID-19 positive non-hospitalized patients with regards to safety and prevention of macro- and micro-thrombotic events using a composite outcome (symptomatic DVT/PE, arterial thromboembolism, MI, CVA, hospitalization for CV/pulmonary events, mortality). Concerns regarding SARS-CoV- 2 transmission risk to research staff and overburdened institutional environments create challenges for standard event monitoring. In addition, safety or outcome events often occur at other institutions rather than the enrollment site. Therefore, research methodology was adapted to effectively evaluate and categorize safety events using a remote low touch approach. Methods Trial over can be found at NCT04498273. Potential adverse events identified through patient electronic data capture survey or call center assessments are handled remotely by central clinical study staff. If an event is identified as a possible endpoint or SAE by the central study staff the electronic data collection (EDC) system notifies the central medical monitoring team, and the enrolling site coordinator if patient enrolled from an acute care setting, that additional source documents are necessary. The medical coordinator works with the site coordinator, or will reach out independently to treating institutions to obtain necessary source documents. Based on a review of clinical data from the EDC and all available source documents, final arbitration of seriousness, relatedness and expectedness is be made by the study's Medical Monitor, and appropriate study entities (NIH, FDA, IRB, study leadership, pharmaceutical co.) are notified.Results The process as described has been successfully and effectively implemented in >50 patients with anticipation of 7000 patient eventual enrollment. Events have been captured, source documentation has been procured and events have been reported as per established protocol processes. Conclusion We have effectively implemented a medical safety event monitoring methodology in a “low touch” study design to assess events in the complex COVID-19 outpatient space. Elements of our system can be effectively replicated in other COVID and non-COVID clinical trials. .

284EMF Thromboelastography to Assess Coagulopathy and Glycocalyx Degradation in Sepsis

Study Objectives: Sepsis is a common and deadly clinical syndrome that affects many patients presenting to the emergency department (ED). Sepsis-induced inflammation leads to abnormal coagulation. Additionally, one potential mechanism for abnormal coagulation and organ dysfunction in sepsis is injury to the endothelial glycocalyx;the glycocalyx contains heparans which are released during degradation and may cause mild coagulopathy. We hypothesize that coagulation abnormalities detected by bedside viscoelastic monitoring (VEM), such as thromboelastography, are associated with organ dysfunction and death (suggesting abnormal coagulation as a mediator). We further hypothesize that heparinase R-time, a VEM measurement that may detect glycocalyx degradation, will be associated with organ dysfunction. Methods: Patients >18 years old with a diagnosis of sepsis were recruited from an urban ED (∼55,000 visits per year) as part of an ongoing observational study of a convenience sample of patients. After informed consent was obtained, blood samples are to measure VEM. VEM measurements include the R time, K time, alpha angle, maximum amplitude (MA), lysis percent at 30 minutes (LY30), and change in R time with the addition of heparinase (ΔR). We also collect demographic information, comorbidities, sepsis severity, the information necessary to determine the Sequential Organ Failure Assessment (SOFA) score, and mortality data. We calculated descriptive statistics for VEM measurements, and Pearson correlations between VEM measurements and SOFA score on enrollment and on days 1-3. Results: We have enrolled 79 subjects thus far (study is ongoing). The baseline VEM parameters, expressed as median (IQR), are as follows: R, 5.3 minutes (4.2-6.4);K, 1.2 minutes (0.9-1.8);alpha angle, 72.0 degrees (65.7-75.8);MA, 68.3 millimeters (63.2-73.5);and LY30, 0.1 percent of maximum amplitude (0-1). The baseline ΔR is 0.4 minutes (IQR, 0.1-55). For patients enrolled to date, ΔR was correlated with day 1 SOFA score (r = -0.21, p < 0.03). Additionally, K was correlated with SOFA score on day 1 (0.22, p < 0.02) and day 2 (0.26, p < 0.03). Further results, delayed due to the impact of coronavirus on this project, will be available at the time of the Research Forum. Conclusion: It is feasible to obtain VEM measurements in patients with sepsis. Our ongoing work will recruit additional patients, measure syndecan-1 levels (a marker of glycocalyx degradation), determine illness severity scores (using Sequential Organ Failure Assessment scores) on days 0-3 and mortality outcomes, and determine whether syndecan-1 levels, VEM measurements, and patient outcome measurements are associated.