Impact of concomitant fluconazole on direct oral anticoagulant bleeding risk.

STUDY OBJECTIVE: The aim of this study was to evaluate the effect on bleeding risk when fluconazole is administered concomitantly with direct oral anticoagulants (DOACs). DESIGN: This was a retrospective cohort study including hospitalized adult patients prescribed a DOAC with or without fluconazole. SETTING: The Ohio State University Wexner Medical Center, a tertiary care academic medical center with more than 1800 beds. PATIENTS: Hospitalized patients ages 18-89 years who received apixaban or rivaroxaban with or without fluconazole from October 1, 2016, to September 30, 2021, were included. The minimum duration of DOAC or DOAC with fluconazole therapy was 48 h. Patients were excluded if they received fluconazole <400 mg daily or a DOAC at doses outside those recommended for atrial fibrillation or venous thromboembolism treatment or prophylaxis. Patients were matched based on DOAC received. INTERVENTION: Patients who received a DOAC with fluconazole were compared with those receiving a DOAC alone. The primary outcome was a composite of major, clinically relevant nonmajor, and minor bleeding events at 30 days. MEASUREMENTS AND MAIN RESULTS: There were 216 patients included, 108 in the DOAC with fluconazole group and 108 in the DOAC alone group. More patients in the DOAC with fluconazole group experienced bleeding at 30 days compared with the DOAC alone group [35/108 (32%) vs. 21/108 (19%), respectively; p = 0.03]; however, after adjusting for proven confounding variables (hemoglobin and concomitant carvedilol) this was found not to be statistically significant [adjusted odds ratio 1.71, 95% confidence interval 0.85-3.40]. CONCLUSIONS: Patients receiving a DOAC with fluconazole were not at significantly increased risk for bleeding at 30 days compared with those receiving a DOAC alone after controlling for confounding variables. As an increasing number of patients are prescribed DOACs, the results of this study may inform clinical decision-making on the safety of concomitant DOAC and fluconazole use.

Safety and Efficacy of Urea for Hyponatremia.

Background and Objective: Urea is an alternative for treatment of hyponatremia however, its use has not been widely studied. The purpose of this study was to evaluate the safety and efficacy of urea for the treatment of hyponatremia. Methods: A retrospective cohort of patients with hyponatremia (serum sodium <135 mEq/L) of any cause who received at least 1 dose of urea during hospitalization and no prior use of urea. Serum sodium levels were collected at baseline and for 4 days or until urea was discontinued, whichever occurred first. The primary outcome was the serum sodium change between baseline and discharge or urea discontinuation. Results: Median serum sodium increased 2 [IQR, 0-4] mEq/L per day after urea administration at a median dose of 30 g/day. A significant difference in serum sodium was observed between baseline and discharge or discontinuation (124.2 ± 4 vs 130.1 ± 5.1; P < .001) and serum blood urea nitrogen (BUN) levels (18.4 ± 13.1 vs 41.1 ± 26.6; P ≤ .001). Serum sodium overcorrection (increase >8 mEq/L in 24 hours) occurred in 6 patients (8%). Urea was discontinued in 39 patients (53%); 20 discontinuations were due to patient intolerance. Conclusion: Urea appears to be an effective treatment for hyponatremia; however, patient tolerance, the rate of serum sodium overcorrection, and outpatient affordability may limit its use.

Anticoagulation Considerations in Liver Disease.

Coagulopathy of liver disease is a complex pathology that may result in thrombosis and/or bleeding complications. Routine laboratory values are not always reflective of the degree of these risks. Additionally, prophylaxis and treatment of venous thromboembolism in patients with cirrhosis require careful evaluation when selecting and monitoring drug therapy for these indications. Therefore, this article aims to provide insight regarding coagulopathy of liver disease, influence on laboratory values, and anticoagulant therapy considerations for critical care nurses assuming care for patients with cirrhosis.