Evaluation of Dosing Regimens of Vancomycin and Aminoglycosides in Pediatric Patients on Continuous Renal Replacement Therapy.

OBJECTIVE: To determine the optimal empiric dosing regimen to achieve therapeutic serum concentrations of vancomycin and aminoglycosides in pediatric patients who are receiving continuous renal replacement therapy (CRRT). METHODS: This retrospective study investigated pediatric patients (<18 years old) who received at least one dose of an aminoglycoside and/or vancomycin while on CRRT and who had at least one serum concentration assessed during the study period. Rates of culture clearance and discontinuation of renal replacement therapy, pharmacokinetic variables (i.e., volume of distribution [Vd], half-life [t½], rate of elimination [ke]), and correlations between patient's age and weight in regard to the empiric dosing regimen were evaluated. RESULTS: Forty-three patients were included in this study. The median dose required to reach therapeutic serum concentrations for vancomycin was 17.6 mg/kg (12.8-20.4 mg/kg) every 12 hours (6-30 hours) in continuous venovenous hemodialysis (CVVHD) patients and 16.3 mg/kg (13.9-21.4 mg/kg) every 12 hours (6-24 hours) in continuous venovenous hemodiafiltration (CVVHDF) patients. The median dose for aminoglycosides was unable to be determined. In CVVHD patients, the median vancomycin ke was 0.04 hr-1, t½ was 18 hours, and Vd was 1.6 L/kg. In CVVHDF patients, the median vancomycin ke was 0.05 hr-1, t½ was 14 hours, and Vd was 0.6 L/kg. No correlation was found between age and weight with regard to effective dosing regimen. CONCLUSIONS: To achieve therapeutic trough concentrations in pediatric patients on CRRT, vancomycin should be dosed at approximately 17.5 mg/kg administered every 12 hours.

Andexanet alfa and four-factor prothrombin complex concentrate for reversal of apixaban and rivaroxaban in patients diagnosed with intracranial hemorrhage.

Limited data exists regarding the clinical outcomes of andexanet alfa and four factor prothrombin complex concentrate (4F-PCC) for reversal of apixaban or rivaroxaban in the setting of intracranial hemorrhage (ICH). The objective of this study was to evaluate clinical outcomes of 4F-PCC and andexanet alfa for reversal of ICH associated with oral factor Xa inhibitors. This was a retrospective, single-center, case series evaluating hemostatic efficacy of patients receiving andexanet alfa) or 4F-PCC for reversal of apixaban or rivaroxaban after ICH. Secondary endpoints included in-hospital mortality, thrombotic complications, timing of reversal agents, intensive care unit and hospital length of stay, patient disposition, and 30-day readmission rate. During the study period, 21 patients received andexanet alfa and 35 received 4F-PCC. Hemostatic efficacy occurred in 64.7% of patients receiving andexanet alfa and 54.8% of receiving 4F-PCC. Thirty-day all-cause mortality was 45.2% for 4F-PCC and 30% for andexanet alfa. Thrombotic events were higher with 4F-PCC (31.4%) compared to andexanet alfa (14.3%). Median time from presentation to administration of reversal agent was 2.67 [1.75-4.13] hours with andexanet alfa and 1.73 [1.21-3.55] hours with 4F-PCC. Discharge to skilled nursing facilities and 30-day readmission were similar between groups. In this cohort, reversal with andexanet alfa and 4F-PCC differed in terms ofhemostatic efficacy and thrombotic events after ICH in patients anticoagulated with apixaban or rivaroxaban.

Reversal agents for oral anticoagulants.

For more than half a century, warfarin, a vitamin K antagonist, has been the anticoagulant of choice. However, direct oral anticoagulants are rapidly gaining in popularity, which poses the need for efficacious reversal agents. This review article summarizes the strategies and agents used to reverse oral anticoagulants.