A prothrombotic coagulopathy is commonly found in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS). A unique feature of COVID-19 respiratory failure is a relatively preserved lung compliance and high Alveolar-arterial oxygen gradient, with pathology reports consistently demonstrating diffuse pulmo-

BACKGROUND: COVID-19 predisposes patients to a prothrombotic state with demonstrated microvascular involvement. The degree of hypercoagulability appears to correlate with outcomes; however, optimal criteria to assess for the highest-risk patients for thrombotic events remain unclear; we hypothesized that deranged thromboelastography measurements of coagulation would correlate with thromboembolic events. STUDY DESIGN: Patients admitted to an ICU with COVID-19 diagnoses who had thromboelastography analyses performed were studied. Conventional coagulation assays, D-dimer levels, and viscoelastic measurements were analyzed using a receiver operating characteristic curve to predict thromboembolic outcomes and new-onset renal failure. RESULTS:Forty-four patients with COVID-19 were included in the analysis. Derangements in coagulation laboratory values, including elevated D-dimer, fibrinogen, prothrombin time, and partial thromboplastin time, were confirmed; viscoelastic measurements showed an elevated maximum amplitude and low lysis of clot at 30 minutes. A complete lack of lysis of clot at 30 minutes was seen in 57% of patients and predicted venous thromboembolic events with an area under the receiver operating characteristic curve of 0.742 (p ¼ 0.021). A D-dimer cutoff of 2,600 ng/mL predicted need for dialysis with an area under the receiver operating characteristic curve of 0.779 (p ¼ 0.005). Overall, patients with no lysis of clot at 30 minutes and a D-dimer > 2,600 ng/mL had a venous thromboembolic event rate of 50% compared with 0% for patients with neither risk factor (p ¼ 0.008), and had a hemodialysis rate of 80% compared with 14% (p ¼ 0.004). CONCLUSIONS: Fibrinolysis shutdown, as evidenced by elevated D-dimer and complete failure of clot lysis at 30 minutes on thromboelastography predicts thromboembolic events and need for hemodialysis in critically ill patients with COVID-19. Additional clinical trials are required to ascertain the need for early therapeutic anticoagulation or fibrinolytic therapy to address this state of fibrinolysis shutdown.

Acute kidney injury (AKI) is a heterogeneous disorder that is common in hospitalized patients and associated with short- and long-term morbidity and mortality. When AKI is present, prompt workup of the underlying cause should be pursued, with specific attention to reversible causes. Measures to prevent AKI include optimization of volume status and avoidance of nephrotoxic medications. Crystalloids are preferred over colloids for most patients, and hydroxyethyl starches should be avoided. Volume overload in the setting of AKI is associated with adverse outcomes, so attention should be paid to overall fluid balance. Currently there are no targeted pharmacotherapies approved for the treatment of AKI. The optimal timing of renal replacement therapy in critically ill patients with AKI is unclear, but is an area of active investigation. Recent studies suggest that AKI is not a "self-limited" process, but is strongly linked to increased risk for chronic kidney disease, subsequent AKI, and future mortality.

0.47 tiM. Following i.p. administration in mice, 7-NI (10-50 mg kg-') produces dose-related antinociception as evidenced by an inhibition of late phase (15-30 min) but not early phase (0-5 min) hindpaw licking time following subplantar injection of formalin (10 pl, 5% v/v). The ED50 for this effect was 26 mg kg-' (equivalent to 159.5 pmol kg-'). Similar i.p. administration of 7-NI (20 and 80 mg kg-') in urethane-anaesthetized mice failed to increase MAP. Thus, 7-NI is a novel inhibitor of NOS which exhibits selectivity for the brain enzyme. Accordingly, 7-NI may be a useful starting point for the development of selective, centrally acting NOS inhibitors devoid of cardiovascular side effects and as a tool to study the central pharmacological effects of nitric oxide (NO).