A Description of Apixaban Dosing Patterns for Treatment or Prevention of Thrombotic Events in Hospitalized Patients on Dialysis.

Introduction: Apixaban is currently the only oral direct factor Xa inhibitor approved for treatment and prevention of venous thromboembolism (VTE) in patients on hemodialysis. Exclusion of dialysis patients from major clinical trials results in prescriber uncertainty regarding the optimal dose of apixaban for VTE treatment in this population. This study sought to characterize the variance in apixaban prescribing patterns for thrombotic indications other than atrial fibrillation. Methods: This retrospective, multi-center, descriptive study analyzed apixaban dosing patterns for hospitalized chronic dialysis patients with history of thrombosis. The primary outcome was incidence of deviation from manufacturer recommendations for dosing, assessed for either a new start or receipt prior to hospitalization. Secondary outcomes included observation of recurrent thrombotic and bleeding event rates during subsequent hospitalizations. Patients were analyzed into subgroups according to type of thrombotic indication for treatment. Data are reported with descriptive statistics. Results: A total of 101 patients were included. Deviations in recommended dosing were observed in 53 of 80 (66.2%) patients receiving apixaban for treatment of acute or chronic thrombosis. Of 44 patients started on apixaban during hospitalization for the indication of acute VTE, a dose deviation was observed in 79.5% of patients. Rates of rehospitalization for recurrent thrombotic events and bleeding were 11.8% and 9.9%, respectively. Conclusion: Variation in apixaban prescribing practices for the treatment of VTE in dialysis patients is common, suggesting an urgent need for prospective studies and updated dosing guidance to optimize safety with apixaban use in this population.

Standard- versus High-Dose Dexmedetomidine for Sedation in the Intensive Care Unit.

Background: Dexmedetomidine is a commonly used sedative in the intensive care unit (ICU), however the use of higher, off label dosing has yet to be elucidated. A dose limitation protocol was implemented at our institution allowing for comparison of dexmedetomidine doses. Objective: The purpose of this study is to evaluate time spent within goal Richmond Agitation Sedation Scale (RASS) range with standard-dosing of dexmedetomidine ≤1 mcg/kg/hour (SD group) compared to high-dose >1 mcg/kg/hour (HD group). Secondary outcomes included days requiring mechanical ventilation, concomitant sedation, and incidence of hypotension or bradycardia. Methods: This retrospective chart review of adult ICU patients at a single academic medical center included patients who required at least 24 hours of mechanical ventilation and received dexmedetomidine monotherapy for at least 4 hours. Patients were excluded for intubations at an outside hospital, continuous neuromuscular blocking infusions, or Glasgow Coma Score ≤4. Results: A total of 144 patients met inclusion criteria (n = 121 SD group and n = 23 HD group). The SD group spent a greater time within goal RASS range compared to the HD group (84.5% [IQR 47-100] vs 45.5% [IQR 30.1-85.4], P = .013). The SD group also had shorter durations of both dexmedetomidine infusion and mechanical ventilation, and required less concomitant sedation. There was no difference in hypotension or bradycardia. Conclusion: This study further adds to the literature that administration of high-dose dexmedetomidine does not appear to confer additional benefit over standard doses for ICU patients requiring mechanical ventilation. Application of this data may support lower institutional maximum doses.

Comparison of Low Dose Recombinant Factor VIIa and 4-Factor Prothrombin Complex Concentrate for Treatment of Bleeding Related to Cardiac Surgery.

Background: Recombinant factor VIIa (rFVIIa) and prothrombin concentrate complex (PCC) are used for uncontrolled bleeding in cardiac surgery (CS), however, there are limited direct comparisons of these agents. Objective: To evaluate the efficacy and safety of rFVIIa and PCC in CS related bleeding. Methods: This retrospective study included adult CS patients who received either low dose rFVIIa (<30 mcg/kg) or 4-factor PCC. The primary outcome was transfusion requirements of packed red blood cells (pRBC) within 6 hours of factor administration. Secondary efficacy outcomes included transfusion requirements 0-18 hours, doses of additional factor product, thrombotic events, and acute kidney injury (AKI). Results: A total of 179 patients were included (n = 78 rFVIIa; n = 101 PCC). Of patients who received blood products, there was no difference in the requirement of pRBCs within 6 hours (73.8 vs 68.9%, P = .5359) or in the median amount of pRBC transfused (500 mL vs 640 mL, P = .0723) in the rFVIIa and PCC groups respectively. Patients in the PCC group were more likely to require additional factor products (24.4% vs 47.5%, P = .0015), develop AKI (12.8% vs 25.7%, P = .0325), have longer ICU lengths of stay [2 (IQR 1-5) vs 4 (IQR 2-6), P = .0487] and greater in-hospital mortality (2.6% vs 10.9%, P = .033). There was no difference in thrombotic events. Conclusion: Although, there was no difference in pRBC transfusion requirements between PCC and rFVIIa, more patients in the PCC group required additional factor products and had increased adverse effects. Further comparisons of PCC and rFVIIa are warranted.

Risk Factors Associated With Acute Kidney Injury in Traumatic Brain Injury Patients Treated With Hypertonic Saline: A Retrospective Study.

Background: Hypertonic saline (HTS) is essential pharmacologic treatment for traumatic brain injury (TBI). Previous studies associate HTS with acute kidney injury (AKI), however evidence in TBIs is limited. Objective: This study examines factors associated with AKI in patients requiring HTS for TBI. Methods: This retrospective study was performed at a Level-1 Trauma, Academic Medical Center. Inclusion criteria were TBI, age ≥12 years, ICU length of stay ≥72 hours, and administration of ≥24 hours of continuous HTS or 500 mL of HTS boluses. The primary outcome was identifying factors associated with AKI. Secondary outcomes included correlation between chloride load and level with development of AKI. Chloride load was calculated from HTS and non-HTS sources. Results: Of 129 patients included, 18 (14%) developed AKI. Maximum sodium level was higher in the AKI group (P < 0.0001). Hyperchloremia (Cl ≥ 115 mEq/L) was more common in the AKI group (100% vs 81%, P = 0.0428). Maximum and change in serum chloride were higher in the AKI group (median 128 vs 123 mEq/L, P = 0.0026 and +24 mEq/L vs +17 mEq/L, P = 0.0084, respectively). Logistic regression analysis indicated an OR 1.095 times higher [95% CI (1.022, 1.172)] for developing AKI for every one mEq/L increase in maximum chloride level and an OR 1.032 [95% CI (1.006, 1.058)] for developing AKI for every 1-year increase in age. There was no difference in total chloride load between groups (P = 0.2143). Non-HTS sources provided more than 40% of total chloride load in both groups. Conclusion: Chloride level, and age may be associated with AKI in TBI patients treated with HTS.

PHarmacist Avoidance or Reductions in Medical Costs in Patients Presenting the EMergency Department: PHARM-EM Study.

To comprehensively classify interventions performed by emergency medicine clinical pharmacists and quantify cost avoidance generated through their accepted interventions. DESIGN: A multicenter, prospective, observational study was performed between August 2018 and January 2019. SETTING: Community and academic hospitals in the United States. PARTICIPANTS: Emergency medicine clinical pharmacists. INTERVENTIONS: Recommendations classified into one of 38 intervention categories associated with cost avoidance. MEASUREMENTS AND MAIN RESULTS: Eighty-eight emergency medicine pharmacists at 49 centers performed 13,984 interventions during 917 shifts that were accepted on 8,602 patients and generated $7,531,862 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established categories were as follows: adverse drug event prevention (1,631 interventions; $2,225,049 cost avoidance), resource utilization (628; $310,582), individualization of patient care (6,122; $1,787,170), prophylaxis (24; $22,804), hands-on care (3,533; $2,836,811), and administrative/supportive tasks (2,046; $342,881). Mean cost avoidance was $538.61 per intervention, $875.60 per patient, and $8,213.59 per emergency medicine pharmacist shift. The annualized cost avoidance from an emergency medicine pharmacist was $1,971,262. The monetary cost avoidance to pharmacist salary ratio was between $1.4:1 and $10.6:1. CONCLUSIONS: Pharmacist involvement in the care of patients presenting to the emergency department results in significant avoidance of healthcare costs, particularly in the areas of hands-on care and adverse drug event prevention. The potential monetary benefit-to-cost ratio for emergency medicine pharmacists is between $1.4:1 and $10.6:1.