Efficacy of Bivalirudin for Therapeutic Anticoagulation in COVID-19 Patients Requiring ECMO Support.

OBJECTIVES: The Coronavirus Disease 2019 (COVID-19) pandemic has been associated with cases of refractory acute respiratory distress syndrome (ARDS) sometimes requiring support with extracorporeal membrane oxygenation (ECMO). Bivalirudin can be used for anticoagulation in patients on ECMO support, but its efficacy and safety in patients with COVID-19 is unknown. The authors set out to compare the pharmacologic characteristics and dosing requirements of bivalirudin in patients requiring ECMO support for ARDS due to COVID-19 versus ARDS from other etiologies. DESIGN AND SETTING: This retrospective case-control study was performed at Indiana University Health Methodist Hospital in Indianapolis, Indiana. PARTICIPANTS: Patients were included if they were on venovenous ECMO support between June 2019 and June 2020, and divided into two groups: ARDS secondary to COVID-19 and those with ARDS from another etiology (Non-COVID). INTERVENTIONS: Patient demographics, such as age, sex, weight, chronic comorbid conditions, baseline antiplatelet and anticoagulant use, antiplatelet use during ECMO, and need for renal replacement therapy were collected, and compared between groups. Time to activated partial thromboplastin time (aPTT) goal, percentage of time at aPTT goal, bivalirudin rates, total bivalirudin requirements, total duration on bivalirudin, total duration on ECMO, mortality, and complications associated with ECMO were collected and compared between groups. MEASUREMENTS AND MAIN RESULTS: A total of 42 patients met inclusion criteria (n = 19 COVID-19, n = 23 non-COVID). However, percentages of aPTTs at goal were maintained more consistently in patients with COVID-19 versus non-COVID (86% v 74%: p < 0.01). Higher median (IQR) daily rates (3.1 µg/kg/min [2.3-5.2] v 2.4 µg/kg/min [1.7-3.3]: p = 0.05) and higher median (IQR) maximum rates of bivalirudin (5 µg/kg/min [3.7-7.5] v 3.8 µg/kg/min [2.5-5]: p = 0.03) were required in the COVID-19 group versus the non-COVID group. Time to goal aPTT was similar between groups. There were no differences in complications associated with anticoagulation, as demonstrated by similar rates of bleeding and thrombosis between both groups. CONCLUSIONS: Patients on ECMO with ARDS from COVID-19 require more bivalirudin overall and higher rates of bivalirudin to maintain goal aPTTs compared with patients without COVID-19. However, COVID-19 patients more consistently maintain goal aPTT. Future randomized trials are needed to support efficacy and safety of bivalirudin for anticoagulation of COVID-19 patients on ECMO.

Fluid Resuscitation and Progression to Renal Replacement Therapy in Patients With COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with respiratory symptoms and renal effects. Data regarding fluid resuscitation and kidney injury in COVID-19 are lacking, and understanding this relationship is critical. OBJECTIVES: To determine if there is an association between fluid volume administered in 24 h and development of renal failure in COVID-19 patients. METHODS: Retrospective chart review; 14 hospitals in Indiana. Included patients were adults admitted between March 11, 2020 and April 13, 2020 with a positive test for severe acute respiratory syndrome coronavirus 2 within 3 days of admission. Patients requiring renal replacement therapy prior to admission were excluded. Volumes and types of resuscitative intravenous fluids in the first 24 h were obtained with demographics, medical history, and other objective data. The primary outcome was initiation of renal replacement therapy. Logistic regression modeling was utilized in creating multivariate models for determining factors associated with the primary outcome. RESULTS: The fluid volume received in the first 24 h after hospital admission was associated with initiation of renal replacement therapy in two different multivariate logistic regression models. An odds ratio of 1.42 (95% confidence interval 1.01-1.99) was observed when adjusting for age, heart failure, obesity, creatinine, bicarbonate, and total fluid volume. An odds ratio of 1.45 (95% confidence interval 1.02-2.05) was observed when variables significant in univariate analysis were adjusted for. CONCLUSIONS: Each liter of intravenous fluid administered to patients with COVID-19 in the first 24 h of presentation was independently associated with an increased risk for initiation of renal replacement therapy, supporting judicious fluid administration in patients with this disease.

Can we predict which COVID-19 patients will need transfer to intensive care within 24 hours of floor admission?

BACKGROUND: Patients with COVID-19 can present to the emergency department (ED) at any point during the spectrum of illness, making it difficult to predict what level of care the patient will ultimately require. Admission to a ward bed, which is subsequently upgraded within hours to an intensive care unit (ICU) bed, represents an inability to appropriately predict the patient's course of illness. Predicting which patients will require ICU care within 24 hours would allow admissions to be managed more appropriately. METHODS: This was a retrospective study of adults admitted to a large health care system, including 14 hospitals across the state of Indiana. Included patients were aged ≥ 18 years, were admitted to the hospital from the ED, and had a positive polymerase chain reaction (PCR) test for COVID-19. Patients directly admitted to the ICU or in whom the PCR test was obtained > 3 days after hospital admission were excluded. Extracted data points included demographics, comorbidities, ED vital signs, laboratory values, chest imaging results, and level of care on admission. The primary outcome was a combination of either death or transfer to ICU within 24 hours of admission to the hospital. Data analysis was performed by logistic regression modeling to determine a multivariable model of variables that could predict the primary outcome. RESULTS: Of the 542 included patients, 46 (10%) required transfer to ICU within 24 hours of admission. The final composite model, adjusted for age and admission location, included history of heart failure and initial oxygen saturation of <93% plus either white blood cell count > 6.4 or glomerular filtration rate < 46. The odds ratio (OR) for decompensation within 24 hours was 5.17 (95% confidence interval [CI] = 2.17 to 12.31) when all criteria were present. For patients without the above criteria, the OR for ICU transfer was 0.20 (95% CI = 0.09 to 0.45). CONCLUSIONS: Although our model did not perform well enough to stand alone as a decision guide, it highlights certain clinical features that are associated with increased risk of decompensation.

Characteristics of COVID-19 patients with bacterial coinfection admitted to the hospital from the emergency department in a large regional healthcare system.

INTRODUCTION: The rate of bacterial coinfection with SARS-CoV-2 is poorly defined. The decision to administer antibiotics early in the course of SARS-CoV-2 infection depends on the likelihood of bacterial coinfection. METHODS: We performed a retrospective chart review of all patients admitted through the emergency department with confirmed SARS-CoV-2 infection over a 6-week period in a large healthcare system in the United States. Blood and respiratory culture results were abstracted and adjudicated by multiple authors. The primary outcome was the rate of bacteremia. We secondarily looked to define clinical or laboratory features associated with bacteremia. RESULTS: There were 542 patients admitted with confirmed SARS-CoV-2 infection, with an average age of 62.8 years. Of these, 395 had blood cultures performed upon admission, with six true positive results (1.1% of the total population). An additional 14 patients had positive respiratory cultures treated as true pathogens in the first 72 h. Low blood pressure and elevated white blood cell count, neutrophil count, blood urea nitrogen, and lactate were statistically significantly associated with bacteremia. Clinical outcomes were not statistically significantly different between patients with and without bacteremia. CONCLUSIONS: We found a low rate of bacteremia in patients admitted with confirmed SARS-CoV-2 infection. In hemodynamically stable patients, routine antibiotics may not be warranted in this population.

Incidence of Venous Thromboembolism in Critically Ill Coronavirus Disease 2019 Patients Receiving Prophylactic Anticoagulation.

OBJECTIVES: One of the defining features of the novel coronavirus disease 2019 infection has been high rates of venous thromboses. The present study aimed to describe the prevalence of venous thromboembolism in critically ill patients receiving different regimens of prophylactic anticoagulation. DESIGN: Single-center retrospective review using data from patients with confirmed severe acute respiratory syndrome coronavirus 2 requiring intubation. SETTING: Tertiary-care center in Indianapolis, IN, United States. PATIENTS: Patients hospitalized at international units Health Methodist Hospital with severe acute respiratory syndrome coronavirus 2 requiring intubation between March 23, 2020, and April 8, 2020, who underwent ultrasound evaluation for venous thrombosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 45 patients were included. Nineteen of 45 patients (42.2%) were found to have deep venous thrombosis. Patients found to have deep venous thrombosis had no difference in time to intubation (p = 0.97) but underwent ultrasound earlier in their hospital course (p = 0.02). Sequential Organ Failure Assessment scores were similar between the groups on day of intubation and day of ultrasound (p = 0.44 and p = 0.07, respectively). D-dimers were markedly higher in patients with deep venous thrombosis, both for maximum value and value on day of ultrasound (p < 0.01 for both). Choice of prophylactic regimen was not related to presence of deep venous thrombosis (p = 0.35). Ultrasound evaluation is recommended if D-dimer is greater than 2,000 ng/mL (sensitivity 95%, specificity 46%) and empiric anticoagulation considered if D-dimer is greater than 5,500 ng/mL (sensitivity 53%, specificity 88%). CONCLUSIONS: Deep venous thrombosis is very common in critically ill patients with coronavirus disease 2019. There was no difference in incidence of deep venous thrombosis among different pharmacologic prophylaxis regimens, although our analysis is limited by small sample size. D-dimer values are elevated in the majority of these patients, but there may be thresholds at which screening ultrasound or even empiric systemic anticoagulation is indicated.