Development and validation of a volumetric absorptive microsampling- liquid chromatography mass spectrometry method for the analysis of cefepime in human whole blood: Application to pediatric pharmacokinetic study.

2020

113002

2020 Feb 05

1873-264X

<p>Cefepime is a fourth-generation cephalosporin antibiotic with an extended spectrum of activity against many Gram-positive and Gram-negative bacteria. There is a growing need to develop sensitive, small volume assays, along with less invasive sample collection to facilitate pediatric pharmacokinetic clinical trials and therapeutic drug monitoring. The volumetric absorptive microsampling (VAMS™) approach provides an accurate and precise collection of a fixed volume of blood (10 μL), reducing or eliminating the volumetric blood hematocrit assay-bias associated with the dried blood spotting technique. We developed a high-performance liquid chromatographic method with tandem mass spectrometry detection for quantification of cefepime. Sample extraction from VAMS™ devices, followed by reversed-phase chromatographic separation and selective detection using tandem mass spectrometry with a 4 min runtime per sample was employed. Standard curves were linear between 0.1-100 μg/mL for cefepime. Intra- and inter-day accuracies were within 95.4-113% and precision (CV) was &lt; 15 % based on a 3-day validation study. Recoveries ranged from 40.8 to 62.1% and the matrix effect was within 89.5-96.7% for cefepime. Cefepime was stable in human whole blood under assay conditions (3 h at room temperature, 24 h in autosampler post-extraction). Cefepime was also stable for at least 1 week (7 days) at 4 °C, 1 month (39 days) at -20 °C and 3 months (91 days) at -78 °C as dried microsamples. This assay provides an efficient quantitation of cefepime and was successfully implemented for the analysis of whole blood microsamples in a pediatric clinical trial.</p>

10.1016/j.jpba.2019.113002

J Pharm Biomed Anal

31785929

A pragmatic checklist to identify pediatric ICU patients at risk for cardiac arrest or code bell activation.

2016

33-7

2016 Feb

1873-1570

<p><strong>BACKGROUND: </strong>In-hospital cardiac arrest is a rare event associated with significant morbidity and mortality. The ability to identify the ICU patients at risk for cardiac arrest could allow the clinical team to prepare staff and equipment in anticipation.</p>

<p><strong>METHODS: </strong>This pilot study was completed at a large tertiary care pediatric intensive care unit to determine the feasibility of a simple checklist of clinical variables to predict deterioration. The daily checklist assessed patient risk for critical deterioration defined as cardiac arrest or code bell activation within 24h of the checklist screen. The Phase I checklist was developed by expert consensus and evaluated to determine standard diagnostic test performance. A modified Phase II checklist was developed to prospectively test the feasibility and bedside provider "number needed to train".</p>

<p><strong>RESULTS: </strong>For identifying patients requiring code bell activation, both checklists demonstrated a sensitivity of 100% with specificity of 76.0% during Phase I and 97.7% during Phase II. The positive likelihood ratio improved from 4.2 to 43.7. For identifying patients that had a cardiac arrest within 24h, the Phase I and II checklists demonstrated a sensitivity of 100% with specificity again improving from 75.7% to 97.6%. There was an improved positive likelihood ratio from 4.1 in Phase I to 41.9 in Phase II, with improvement of "number needed to train" from 149 to 7.4 providers.</p>

<p><strong>CONCLUSIONS: </strong>A novel high-risk clinical indicators checklist is feasible and provides timely and accurate identification of the ICU patients at risk for cardiac arrest or code bell activation.</p>

10.1016/j.resuscitation.2015.11.017

Resuscitation

26703460