BACKGROUND Patients with liver disease are concomitantly at increased risk of venous thromboembolism (VTE) and bleeding events due to changes in the balance of pro- and anti-hemostatic substances. As such, recommendations for the use of pharmacological VTE prophylaxis are lacking. Recent studies have found no difference in rates of VTE in those receiving and not receiving pharmacological VTE prophylaxis, though most studies have been small. Thus, our study sought to establish if pharmacological VTE prophylaxis is effective and safe in patients with liver disease. AIM To determine if there is net clinical benefit to providing pharmacological VTE prophylaxis to cirrhotic patients. METHODS In this retrospective study, 1806 patients were propensity matched to assess if pharmacological VTE prophylaxis is effective and safe in patients with cirrhosis. Patients were divided and evaluated based on receipt of pharmacological VTE prophylaxis. RESULTS The composite primary outcome of VTE or major bleeding was more common in the no prophylaxis group than the prophylaxis group (8.7% vs 5.1%, P = 0.002), though this outcome was driven by higher rates of major bleeding (6.9% vs 2.9%, P < 0.001) rather than VTE (1.9% vs 2.2%, P = 0.62). There was no difference in length of stay or in-hospital mortality between groups. Pharmacological VTE prophylaxis was independently associated with lower rates of major bleeding (OR = 0.42, 95%CI: 0.25-0.68, P = 0.0005), but was not protective against VTE on multivariable analysis. CONCLUSION Pharmacological VTE prophylaxis was not associated with a significant reduction in the rate of VTE in patients with liver disease, though no increase in major bleeding events was observed.

Introduction:Positive hemodynamic response to vasopressin after 6 hours of infusion was independently associated with lower mortality in a previous retrospective study of patients with septic shock. However, factors previously associated with higher plasma vasopressin concentration were not associated with response, and the relationship between plasma vasopressin concentration and hemodynamic response has not been evaluated. Objectives:This cross-sectional study compared plasma vasopressin concentrations in hemodynamic responders and non-responders to vasopressin in patients with septic shock to evaluate plasma vasopressin concentration as a therapeutic target for hemodynamic response to vasopressin.Methods: Adult patients with septic shock were included if they were treated with fixed-dose vasopressin as an adjunct to catecholamines for at least 3 hours. Patients were assigned to groups based on vasopressin response.Results: Ten hemodynamic responders to vasopressin and eight non-responders were included. Blood samples for plasma vasopressin concentration were collected 3 to 6 hours after vasopressin initiation. Baseline characteristics were similar between groups. No difference was detected in plasma vasopressin concentrations between hemodynamic responders and non-responders (median 88.6 pg/ml [interquartile range (IQR) 84.4, 107.5 pg/ml] vs 89.9 pg/ml [IQR 67.5, 157.4 pg/ml],

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Background: Essential to the coagulation pathway, vitamin K (phytonadione) is used to correct clotting factor deficiencies and for reversal of warfarin-induced bleeding. In practice, high-dose intravenous (IV) vitamin K is often used, despite limited evidence supporting repeated dosing. Objective: This study sought to characterize differences in responders and nonresponders to high-dose vitamin K to guide dosing strategies. Methods: This was a case-control study of hospitalized adults who received vitamin K 10 mg IV daily for 3 days. Cases were represented by patients who responded to the first dose of IV vitamin K and controls were nonresponders. The primary outcome was change in international normalized ratio (INR) over time with subsequent vitamin K doses. Secondary outcomes included factors associated with response to vitamin K and incidence of safety events. The Cleveland Clinic Institutional Review Board approved this study. Results: There were 497 patients included, and 182 were responders. Most patients had underlying cirrhosis (91.5%). In responders, the INR decreased from 1.89 at baseline (95% CI = [1.74-2.04]) to 1.40 on day 3 (95% CI = [1.30-1.50]). In nonresponders, the INR decreased from 1.97 (95% CI = [1.83-2.13]) to 1.85 ([1.72-1.99]). Factors associated with response included lower body weight, absence of cirrhosis, and lower bilirubin. There was a low incidence of safety events observed. Conclusions: In this study of mainly patients with cirrhosis, the overall adjusted decrease in INR over 3 days was 0.3, which may have minimal clinical impact. Additional studies are needed to identify populations who may benefit from repeated daily doses of high-dose IV vitamin K.

Background: Vancomycin pharmacokinetics are altered in the critically ill and are further distorted by renal replacement therapy. Limited literature is available evaluating vancomycin dosing in continuous veno-venous hemodialysis (CVVHD). Objective: The goal of this analysis was to identify factors that affect vancomycin trough concentration in patients on CVVHD and to determine an appropriate dosing strategy. Methods: This was a single-center, retrospective cohort study of adult inpatients admitted to the Cleveland Clinic from May 2016-December 2017. Patients in the intensive care unit who received ≥ 2 doses of vancomycin during CVVHD were included. Patients with interruptions of CVVHD inappropriately timed troughs, a change in dialysate rate, and those who received different vancomycin dosages were excluded. Multivariable linear regression including age, sex, weight, Sequential Organ Failure Assessment score, albumin, 24-hour urine output (UOP), dialysate rate, filter type, and vancomycin dose was run to determine predictors of vancomycin concentration. Results: A total of 160 patients were included. The median vancomycin dose was 12.6 mg/kg with a trough of 24.6 mcg/mL. Weight, 24-hour UOP, vancomycin dose (mg/kg), and dialysate rate (mL/kg/h) were all determined to be independent predictors of vancomycin trough level. Patients who received <10 mg/kg doses of vancomycin (N=18) achieved a median trough of 21.5 mcg/mL, with 83% being therapuetic. In patients who received >10 mg/kg (N=142), the median trough was 25.5 mcg/mL, with 47% being therapeutic. Conclusion and Relevance: Vancomycin dose, dialysate rate, UOP, and weight are independently associated with vancomycin trough concentration. In CVVHD patients, vancomycin dosed at 10 mg/kg every 24 hours may be an appropriate recommendation.