M A Frölich1, D M Dennis, J A Shuster, R J Melker. 1. Department of Anesthesiology, University of Florida Colleges of Medicine and Engineering, Gainesville, Florida, USA. froelich@uab.edu
Abstract
BACKGROUND: The purpose of this study is to test precision and systematic bias of a target controlled infusion (TCI) of propofol in human volunteers at two sedative concentrations. METHODS: We studied the 'Diprifusor' model (Marsh Pharmacokinetics and a Graseby 3400 infusion pump) in 18 human volunteers at two sedative target plasma concentrations (0.5 and 1.0 microg ml(-1)). Twenty minutes after infusion start or change and 20 min after discontinuation of the infusion plasma propofol concentrations were measured using liquid chromatography-mass spectroscopy (LC-MS). Plasma propofol concentrations were compared with concentrations predicted by the TCI system. Agreement of those two measures (precision and bias) was determined using regression analysis. RESULTS: We found little systematic bias but poor precision. When setting the TCI system to deliver a plasma concentration of 1.0 microg ml(-1) one can predict the actual plasma concentration with 95% confidence only within a range of 0.44-1.38 microg ml(-1). CONCLUSIONS: This finding helps to explain differences in responses to propofol sedation; pharmacokinetic variability appears to be an important factor.
BACKGROUND: The purpose of this study is to test precision and systematic bias of a target controlled infusion (TCI) of propofol in human volunteers at two sedative concentrations. METHODS: We studied the 'Diprifusor' model (Marsh Pharmacokinetics and a Graseby 3400 infusion pump) in 18 human volunteers at two sedative target plasma concentrations (0.5 and 1.0 microg ml(-1)). Twenty minutes after infusion start or change and 20 min after discontinuation of the infusion plasma propofol concentrations were measured using liquid chromatography-mass spectroscopy (LC-MS). Plasma propofol concentrations were compared with concentrations predicted by the TCI system. Agreement of those two measures (precision and bias) was determined using regression analysis. RESULTS: We found little systematic bias but poor precision. When setting the TCI system to deliver a plasma concentration of 1.0 microg ml(-1) one can predict the actual plasma concentration with 95% confidence only within a range of 0.44-1.38 microg ml(-1). CONCLUSIONS: This finding helps to explain differences in responses to propofol sedation; pharmacokinetic variability appears to be an important factor.
Authors: Fiona Marie Burton; David John Lowe; Jonathan Millar; Alasdair R Corfield; Malcolm J Watson; Malcolm A B Sim Journal: Emerg Med J Date: 2020-12-09 Impact factor: 2.740