Evaluation of dosing and safety outcomes of low-dose prophylactic warfarin in children after cardiothoracic surgery.

PURPOSE: Prophylactic warfarin with an International Normalized Ratio (INR) goal of 1.5 to 2.0 is one antithrombotic therapy utilized in children after cardiothoracic surgery (CTS); published sources suggest a dose of 0.1 mg/kg per day to achieve this goal. However, few studies have evaluated dosing in this population. The purpose of this study was to evaluate dosing and safety outcomes in children receiving warfarin after CTS. METHODS: A descriptive, retrospective review was conducted to evaluate warfarin dosing and INR outcomes in patients 18 years of age or younger who underwent CTS and received prophylactic warfarin with an INR goal of 1.5 to 2.0 from January 2014 through December 2018. The primary objective was to determine the median initial warfarin dose. Secondary objectives included identifying the percentage of documented INR values that were outside the therapeutic range, the percentage of patients with therapeutic INRs at discharge, and the 30-day readmission rate. RESULTS: Twenty-six patients were included in the review. The median initial warfarin dosage was 0.07 mg/kg/d (interquartile range [IQR], 0.05-0.10 mg/kg/d). Of the total of 177 INR values collected during the entire study period, 67 (37.9%) were therapeutic, 64 (36.2%) were subtherapeutic, and 46 (26.0%) were supratherapeutic. Eighteen patients (69.2%) had at least 1 supratherapeutic INR at any point during the study period, most frequently on days 2 through 4 of therapy. At discharge, 11 patients (42.3%) had therapeutic INRs. Four patients (15.4%) were readmitted within 30 days, with bleeding documented in 2 patients during their readmission. CONCLUSION: The majority of patients received an initial warfarin dose less than that specified in published recommendations but still had a supratherapeutic INR at least once during the study period. When initiating warfarin after CTS, a dosage of <0.1 mg/kg per day and frequent monitoring may be needed to achieve an INR goal of 1.5 to 2.0.

Prevalence of Unrounded Medication Doses and Associated Factors Among Hospitalized Pediatric Patients.

OBJECTIVES: This study aims to determine the prevalence and factors associated with unrounded doses ordered via a computerized prescriber order entry (CPOE) system among children during a 1-week reference period. METHODS: This retrospective, cross-sectional study included children younger than 18 years admitted during a 7-day period. An unrounded dose was defined as an unrounded actual dose (eg, dose calculated to the tenths place for non-neonatal intensive care (non-NICU) patients and dose calculated to the hundredth place for NICU patients) or unrounded volume per dose [eg, <0.1 mL for non-NICU patients and <0.01 mL for NICU patients]. A multilevel logistic regression model was used to determine the prevalence and factors associated with unrounded doses via a CPOE system with adjustment for clustering effects. RESULTS: A total of 395 patients were admitted with 391 receiving medications. The overall prevalence of unrounded doses was 30% among the 2426 doses administered. Patients on the NICU team had the highest prevalence of unrounded doses. The odds of an unrounded dose were 4% (adjusted odds ratio, 0.96; 95% confidence interval, 0.94-0.98) lower with each additional kilogram increase in weight after controlling for age, route, scheduled versus as-needed administration, and cluster effects. CONCLUSIONS: The prevalence of unrounded doses was higher than in previous studies. It was higher in smaller children after controlling for age, medication-related variables, and clustering. Future studies should focus on the role of CPOE in preventing unrounded and unmeasurable doses and if these strategies affect clinical outcomes (eg, adverse drug events).

Peramivir for the treatment of influenza.

Peramivir (BioCryst Pharmaceuticals) is a novel investigational intravenous neuraminidase inhibitor that exhibits potent antiviral activity against influenza A and B viruses. Peramivir is created by a structure-based drug design and consists of a cyclopentane backbone with a positively charged guanidinyl group and lipophilic side chains. Peramivir was made available in the USA through the Emergency Investigational New Drug regulations and under an Emergency Use Authorization for hospitalized patients with known or suspected influenza during the 2009 H1N1 influenza pandemic. In trials involving ambulatory adult subjects, intravenous peramivir is safe and has a pharmacokinetic profile that supports once-daily dosing. The drug is licensed in Japan and South Korea and is currently undergoing Phase III trials in the USA. Viral resistance mechanisms to peramivir have not been fully delineated and ongoing surveillance is important. Given the serious health threat of influenza at all ages and limitations in vaccine delivery, peramivir is a promising addition to the currently limited treatment options for the treatment of severe influenza infection.