BACKGROUND: Coronavirus disease-2019 (COVID-19) is associated with hypercoagulability and increased thrombotic risk in critically ill patients. To our knowledge, no studies have evaluated whether aspirin use is associated with reduced risk of mechanical ventilation, intensive care unit (ICU) admission, and in-hospital mortality. METHODS: A retrospective, observational cohort study of adult patients admitted with COVID-19 to multiple hospitals in the United States between March 2020 and July 2020 was performed. The primary outcome was the need for mechanical ventilation. Secondary outcomes were ICU admission and in-hospital mortality. Adjusted hazard ratios (HRs) for study outcomes were calculated using Cox-proportional hazards models after adjustment for the effects of demographics and comorbid conditions. RESULTS: Four hundred twelve patients were included in the study. Three hundred fourteen patients (76.3%) did not receive aspirin, while 98 patients (23.7%) received aspirin within 24 hours of admission or 7 days before admission. Aspirin use had a crude association with less mechanical ventilation (35.7% aspirin versus 48.4% nonaspirin, P = .03) and ICU admission (38.8% aspirin versus 51.0% nonaspirin, P = .04), but no crude association with in-hospital mortality (26.5% aspirin versus 23.2% nonaspirin, P = .51). After adjusting for 8 confounding variables, aspirin use was independently associated with decreased risk of mechanical ventilation (adjusted HR, 0.56, 95% confidence interval [CI], 0.37-0.85, P = .007), ICU admission (adjusted HR, 0.57, 95% CI, 0.38-0.85, P = .005), and in-hospital mortality (adjusted HR, 0.53, 95% CI, 0.31-0.90, P = .02). There were no differences in major bleeding (P = .69) or overt thrombosis (P = .82) between aspirin users and nonaspirin users. CONCLUSIONS: Aspirin use may be associated with improved outcomes in hospitalized COVID-19 patients. However, a sufficiently powered randomized controlled trial is needed to assess whether a causal relationship exists between aspirin use and reduced lung injury and mortality in COVID-19 patients.

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Background Delirium is a frequent manifestation of acute brain dysfunction and is associated with cognitive impairment. The hypothesized mechanism of brain dysfunction during critical illness is centered on neuroinflammation, regulated in part by the cholinergic system. Point-of-care serum cholinesterase enzyme activity measurements serve as a real-time index of cholinergic activity. We hypothesized that cholinesterase activity during critical illness would be associated with delirium in the intensive care unit (ICU) and cognitive impairment after discharge. Methods We enrolled adults with respiratory failure and/or shock and measured plasma acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity on days 1, 3, 5, and 7 after enrollment. AChE values were also normalized per gram of hemoglobin (AChE/Hgb). We assessed for coma and delirium twice daily using the Richmond Agitation Sedation Scale and the Confusion Assessment Method for the ICU to evaluate daily mental status (delirium, coma, normal) and days alive without delirium or coma. Cognitive impairment, disability, and health-related quality of life were assessed at up to 6 months post-discharge. We used multivariable regression to determine whether AChE, AChE/Hgb, and BChE activity were associated with outcomes after adjusting for relevant covariates. Results We included 272 critically ill patients who were a median (IQR) age 56 (39–67) years and had a median Sequential Organ Failure Assessment score at enrollment of 8 (5–11). Higher daily AChE levels were associated with increased odds of being delirious versus normal mental status on the same day (Odds Ratio [95% Confidence Interval] 1.64 [1.11, 2.43]; P = 0.045). AChE/Hgb and BChE activity levels were not associated with delirious mental status. Lower enrollment BChE was associated with fewer days alive without delirium or coma (P = 0.048). AChE, AChE/Hgb, and BChE levels were not significantly associated with cognitive impairment, disability, or quality of life after discharge. Conclusion Cholinesterase activity during critical illness is associated with delirium but not with outcomes after discharge, findings that may reflect mechanisms of acute brain organ dysfunction. Trial Registration: NCT03098472. Registered 31 March 2017.

Background: Tranexamic acid (TXA) administration is recommended in severely injured trauma patients. We examined TXA administration, admission fibrinolysis phenotypes, and clinical outcomes following traumatic injury and hypothesized that TXA was associated with increased multiple organ failure (MOF). Methods: Two-year, single-center, retrospective investigation. Inclusion criteria were age 18 years, Injury Severity Score (ISS) >16, admitted from scene of injury, thromboelastography within 30 min of arrival. Fibrinolysis was evaluated by lysis at 30 min (LY30) and fibrinolysis phenotypes were defined as: Shutdown: LY30 0.8%, Physiologic: LY30 0.81-2.9%, Hyperfibrinolysis: LY30 3.0%. Primary outcomes were 28-day mortality and MOF. The association of TXA with mortality and MOF was assessed among the entire study population and in each of the fibrinolysis phenotypes. Results: Four hundred twenty patients: 144/420 Shutdown (34.2%), 96/420 Physiologic (22.9%), and 180/410 Hyperfibrinolysis (42.9%). There was no difference in 28day mortality by TXA administration among the entire study population (P ¼ 0.52). However, there was a significant increase in MOF in patients who received TXA (11/46, 23.9% vs 16/374, 4.3%; P < 0.001). TXA was associated MOF (OR: 3.2, 95% CI 1.2-8.9), after adjusting for confounding variables. There was no difference in MOF in patients who received TXA in the Physiologic (1/5, 20.0% vs 7/91, 7.7%; P ¼ 0.33) group. There was a significant increase in MOF among patients who received TXA in the Shutdown (3/11, 27.3% vs 5/133, 3.8%; P ¼ 0.001) and Hyperfibrinolysis (7/30, 23.3% vs 5/150, 3.3%; P ¼ 0.001) groups. Conclusions: Administration of TXA following traumatic injury was associated with MOF in the fibrinolysis shutdown and hyperfibrinolysis phenotypes and warrants continued evaluation.