Clinical Outcomes in Critically-Ill Patients with COVID-19 Treated with Therapeutic Dose of Anticoagulants for Suspected Thromboembolism

Introduction Since March 2020, the New York City hospitals have experienced a tremendous surge of COVID-19 cases. Our hospital admitted 877 patients in a 2-week period, from March 15 to Apr 1, 2020. The exact mechanism of how COVID-19 causes vascular injury is unclear but some experts attribute it to widespread vascular inflammation[2,3]. The limited understanding of the hypercoagulable mechanism has limited our treatment techniques. To date, whether therapeutic anticoagulation is the right choice in regard to optimal management of patients with COVID-19 in suspected but not confirmed DVT (deep vein thrombosis) or PE (pulmonary embolism) is still a question[4]. Method We performed a retrospective observational cohort analysis of 145 adult ICU patients at an acute care teaching hospital located in Queens County, New York between March 15, 2020 to April 1, 2020. The study was approved by IRB. All patients >18 years of age with confirmed SARS-CoV-2 infection and determined to require admission to intensive care units between March 15, 2020 and April 1, 2020, inclusive of those dates, were included in the investigation, with the exclusion of pregnant patients. All data was collected from the electronic health record (Allscripts) and was compiled in REDCap software for data encryption. During that study period, therapeutic anticoagulants were used in hospitalized patients with COVID-19 with high clinical risk or suspicion for venous thromboembolism (VTE). As per hospital protocol, heparin continuous infusion with a target activated partial thromboplastin time of 50 to 70 seconds or enoxaparin 1mg/kilogram(kg) twice a day for creatinine clearance (CrCl) above 30 ml/min or once a day for CrCl below 30 ml/min were used to achieve therapeutic anticoagulation. The primary outcome of the study was 28-day in-hospital mortality for critically ill patients affected by COVID-19 with or without the use of therapeutic anticoagulation. Covariates included in analysis were hypertension, diabetes, hyperlipidemia, cardiac history, and use of antiplatelet and anticoagulant medications prior to admission. Statistical analysis was done using R version 4.0.2. Results Out of 145 ICU patients, 61 received therapeutic anticoagulation. Kaplan-Meier survival curves show the survival probability with respect to days after admission for the two groups (those who used anticoagulant therapeutic drugs and those who didn't) using 28-day in-hospital mortality.(Fig 1) Median age for patients was 61 years for patients who didn't receive therapeutic anticoagulants compared to 60 years for patients who received therapeutic doses. The mean D-dimer among patients who received therapeutic anticoagulation was 20462 ng/ml (D-dimer units) compared to 7872 ng/ml for those who did not. The median number of days of survival for those who did not take anticoagulant therapeutic drugs is 10 days, while the median for those who did take anticoagulant therapeutic drugs is 25 days. After adjusting for hypertension, diabetes, hyperlipidemia, cardiac history, home antiplatelet medication use and continuous response for peak d-dimer levels, the results also show that there is a causal effect of 22.2 % decreased risk of 28-day in-hospital mortality if one received the therapeutic anticoagulant in the hospital. Conclusion Our findings suggest that there is a significantly higher median survival time in critically ill patients who received therapeutic anticoagulants in the hospital compared to those who didn't. However, our study is limited by observational nature, possible unobserved confounding, lack of metrics to classify illness severity as well as lack of evidence based decision guideline in initiation of therapeutic anticoagulation. There is an urgent need for further evidence-based studies like clinical trials which are necessary to provide specific guidelines for use of therapeutic anticoagulants in patients with COVID-19 infection. References 1. Becker RC. COVID-19 update: Covid-19-associated coagulopathy. J Thromb Thrombolysis. 2020;50(1):54-67. 2. Tay, M.Z., Poh, C M., Rénia, L. et al. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol 20, 363-374 (2020). 3. Lisa K. Moores, Tobias Tritschler, et al. Prevention, Diagnosis, and Treatment of VTE in Patients With Coronavirus Disease 2019: CHEST Guideline and Expert Panel Report, Chest, Volume 158, Issue 3, 2020, Pages 1143-1163, ISSN 0012-3692. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

TIMING OF INTUBATION AND OUTCOME IN THE COVID-19 PANDEMIC: CHALLENGING THE CONCEPT OF PERMISSIVE HYPOXEMIA

SESSION TITLE: Critical Care Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: After the novel coronavirus disease (COVID-19), was declared a pandemic, New York quickly became the new epicenter of the disease, with Queens County reporting the most confirmed cases in the United States. This study was conducted during the peak of COVID-19 in Queens. Due to the severity of the disease and limited resources, patients were intubated at varying degrees of oxygenation. This study examines the preoxygenation state of COVID-19 ARDS patients prior to intubation and its implication on clinical outcomes. METHODS: At a single acute tertiary care hospital located in Queens, New York, all patients admitted between March 15 and April 15, 2020 were screened. Active COVID-19 status was confirmed with reverse transcriptase-polymerase chain reaction assay on nasopharyngeal samples. All COVID-19 patients who were intubated with documented pre-intubation oxygen saturation (PreO2) were included. All data were collected from the electronic health record, including laboratory data, ventilator settings, and hospital course. Peri-intubation cardiac arrest events up to 24 hours post-intubation and mortality during the study period were examined as outcomes. Data was analyzed with SPSS (version 25). Continuous variables were tested using independent T-tests. All tests of significance were two-tailed, and a p-value of 0.05 was considered significant. RESULTS: A total of 192 patients were included in the study. They had a mean age of 61.2 ± 12.2 years, and 130 (64.1%) were men. The mean preO2 of all patients was 71.3 ± 13.6, and the mean peri-intubation PF ratio was 120.84 ± 58.6. 32 out of 192 patients (16.7%) with peri-intubation cardiac arrest demonstrated significantly lower preO2 (p=0.03) compared to those without. These 32 patients also demonstrated more days with symptoms prior to intubation (p=0.004). 121 patients who expired during the clinical course demonstrated lower PreO2 (p=0.60) and PF Ratios (p=0.48) compared to the 71 patients who did not, but these comparisons were not statistically significant. Patients who expired demonstrated fewer symptomatic days prior to intubation than those who did not, but this was not statistically significant (p=0.06). CONCLUSIONS: At the time of intubation, the patients had significant hypoxemia and severe ARDS by PF ratio. Lower oxygenation prior to intubation is associated with an increase in peri-intubation complications. CLINICAL IMPLICATIONS: Due to unclear pathophysiology of ARDS in COVID-19, the optimal timing of intubation continues to be debated. Physicians should consider intubation earlier in the disease course prior to significant hypoxemia, which may have a negative impact on peri-intubation complications. Clinical outcome was further impacted by the restriction on preoxygenation of the patients prior to intubation, given its risk of viral aerosolization. Means of preoxygenating with minimal risk of disease spread should continue to be explored. DISCLOSURES: Advisory Committee Member relationship with Ambu Please note: $1-$1000 by Olumayowa Abe, source=Admin input, value=Honoraria No relevant relationships by Ahmed Al-Ghrairi, source=Web Response No relevant relationships by Christian Castaneda, source=Web Response No relevant relationships by Ettaib El Marabti, source=Web Response No relevant relationships by Hadya Elshakh, source=Web Response No relevant relationships by Teressa Ju, source=Web Response No relevant relationships by Michael Karass, source=Admin input No relevant relationships by Miri Kim, source=Web Response No relevant relationships by Jack Mann, source=Web Response No relevant relationships by Christina Jee Ah Rhee, source=Web Response No relevant relationships by Fizza Sajid, source=Web Response No relevant relationships by Angelina Voronina, source=Web Response

SELF-EXTUBATION RATE AND SEDATION REQUIREMENT IN COVID-19

SESSION TITLE: Critical Care Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: After the novel coronavirus disease (COVID-19), was declared a pandemic, New York quickly became the new epicenter of the disease. This study was conducted during the peak of COVID-19 in Queens. Many COVID-19 patients with severe acute respiratory distress syndrome (ARDS) required endotracheal intubation and heavy sedation for prolonged periods of time. Unplanned extubation (UE) events have a notable impact on clinical course and outcome. [1] Self-extubation (SE) is the most common reason for UE, and inadequate sedation is one of its most significant risk factors. [1,2] This study examines factors associated with SE events in patients with ARDS in COVID-19. METHODS: At a single acute tertiary care hospital located in Queens, New York, all patients with SARS-CoV-2 infection admitted between March 15, 2020 and April 15, 2020, were screened. Active COVID-19 status was confirmed with reverse transcriptase-polymerase chain reaction assay performed on nasopharyngeal samples. All patients who underwent endotracheal intubation were included in the study. All data were collected from the electronic health record for 28-day outcomes. All UE events, including SE and other causes for UE, number and dosages of sedatives at the time of SE, adverse events, such as cardiac arrest and anoxic brain injury following UE, were examined. RESULTS: A total of 205 patients were included in the study. Of these, 24 patients (11.7%) had one or more UE. Nine were due to SE (4.4%). None of these patients had plans for extubation. Only one was not on sedation due to a delay on the general medicine floor. The rest were sedated on 2 or more sedatives, including continuous infusions of opioids, propofol, dexmedetomidine, and ketamine at high doses. (Table 1) Five patients out of 9 with SE got reintubated right after SE event (55.6%). Two patients with SE events did not require reintubation (22.2%). There were 2 cardiac arrests following 9 SE events (22.2%), and only 1 patient survived. The 28-day mortality for patients with SE and patients without any UE were 66.7 % and 62%, respectively. CONCLUSIONS: Multiple SE events occurred in ARDS in COVID-19 patients, who were on multiple sedatives without any plans for extubation trial. In comparison with SE in other ARDS patients, these patients required higher doses of sedatives to achieve adequate sedation. SE events also had a significant rate of complication. Although this study is limited by its small sample size, it provides a narrative of what the experience has been with the COVID-19 patients. This highlights the need for further studies with higher statistical power in order to better understand the disease characteristics. CLINICAL IMPLICATIONS: Critical care physicians should consider tracheostomy in ARDS patients with COVID-19, to prevent complications of heavy sedation required for endotracheal intubation and complications of SE. DISCLOSURES: Advisory Committee Member relationship with Ambu Please note: $1-$1000 by Olumayowa Abe, source=Admin input, value=Honoraria No relevant relationships by Ahmed Al-Ghrairi, source=Web Response No relevant relationships by Ettaib El Marabti, source=Web Response No relevant relationships by Hadya Elshakh, source=Web Response No relevant relationships by Teressa Ju, source=Web Response No relevant relationships by Michael Karass, source=Admin input No relevant relationships by Miri Kim, source=Web Response No relevant relationships by Jack Mann, source=Web Response No relevant relationships by Christina Jee Ah Rhee, source=Web Response No relevant relationships by Fizza Sajid, source=Web Response No relevant relationships by Angelina Voronina, source=Web Response

OUTCOME OF EXTUBATION ATTEMPTS AND DAYS WITH ENDOTRACHEAL VENTILATION IN COVID-19

SESSION TITLE: Critical Care Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: As of May 2020, Queens County, New York reported the most confirmed cases of the novel coronavirus disease (COVID-19) in the United States. This study was conducted during the peak of COVID-19 in Queens. Many COVID-19 patients with acute respiratory distress syndrome (ARDS) required mechanical ventilation via endotracheal intubation for extended periods of time. This study examines the length of ventilation via endotracheal tube (ETT) and the outcome of extubation attempts (EXA). METHODS: At a single acute tertiary care hospital located in Queens, New York, all patients with COVID-19 admitted between March 15 to April 15, 2020, who were intubated with ETT were included. All data were collected from the electronic health record until April 25, 2020. Hospital course, extubation events, reintubation events, and number of tracheostomies were gathered. Number of ventilated days via ETT and mortality were studied as outcomes. Patients were divided into those who expired with ETT, were successfully extubated at first EXA, failed EXA, and underwent tracheostomy. Cardiac arrest and anoxic brain injury were studied as adverse events. RESULTS: 205 patients were included. Their mortality was 63.4% with 130 in-hospital deaths, of which 110 patients (54.7%) expired while on ventilator via ETT. 13 out of 205 patients (5.4%) were successfully extubated on first attempt, of which 2 were unplanned self-extubation events. The average ventilated days via ETT for this group was 9.36 days (SD 4.7 days). 7 out of 205 patients (3.4%) failed EXA. The average time to EXA in this group was 9.29 days (SD 5.8 days). There were 0 reported cardiac arrests or anoxic brain injuries following EXA. The average time from EXA to reintubation was 1.14 days (SD 1.9 days). 2 of the 7 patients who failed EXA expired on ventilator support via ETT. 36 out of 205 patients underwent tracheostomy. The mortality rate for this group was 19.4% (SD). The average ventilated days via ETT was 16.2 days (SD 5.3 days). CONCLUSIONS: COVID-19 patients that were intubated for severe ARDS had a notable mortality rate, and those who survived required a prolonged course of ventilation. Both groups of successful extubation and failed extubation had similar time on endotracheal ventilation prior to the attempt, making it an unlikely factor determining successful extubation. Patients who were able to undergo tracheostomy had lower mortality, but it is unclear if there was a direct correlation, as patients were generally less ill to be able to undergo such a procedure. CLINICAL IMPLICATIONS: Patients with severe ARDS in COVID-19 required a prolonged course of mechanical ventilation and exhibited a high likelihood of failure to extubate. In order to avoid the complications of prolonged ventilation via ETT, early tracheostomy should be considered. In the future, a larger cohort of patients should be examined to provide statistical reinforcement of our findings. DISCLOSURES: Advisory Committee Member relationship with Ambu Please note: $1-$1000 by Olumayowa Abe, source=Admin input, value=Honoraria No relevant relationships by Ahmed Al-Ghrairi, source=Web Response No relevant relationships by Christian Castaneda, source=Web Response No relevant relationships by Ettaib El Marabti, source=Web Response No relevant relationships by Hadya Elshakh, source=Web Response No relevant relationships by Teressa Ju, source=Web Response No relevant relationships by Michael Karass, source=Admin input No relevant relationships by Miri Kim, source=Web Response No relevant relationships by Jack Mann, source=Web Response No relevant relationships by Christina Jee Ah Rhee, source=Web Response No relevant relationships by Fizza Sajid, source=Web Response No relevant relationships by Angelina Voronina, source=Web Response