The relationship between the effect-site concentration of propofol and sedation scale in children: a pharmacodynamic modeling study

BACKGROUND: Continuous infusion of propofol has been used to achieve sedation in children. However, the relationship between the effect-site concentration (C(e)) of propofol and sedation scale has not been previously examined. The objective of this study was to investigate the relationship between the C(e) of propofol and the University of Michigan Sedation Scale (UMSS) score in children with population pharmacodynamic modeling. METHODS: A total of 30 patients (aged 3 to 6 years) who underwent surgery under general anesthesia with propofol and remifentanil lasting more than 1 h were enrolled in this study. Sedation levels were evaluated using the UMSS score every 20 s by a 1 μg/mL stepwise increase in the C(e) of propofol during the induction of anesthesia. The pharmacodynamic relationship between the C(e) of propofol and UMSS score was analyzed by logistic regression with nonlinear mixed-effect modeling. RESULTS: The estimated C(e50) (95% confidence interval) of propofol to yield UMSS scores equal to or greater than n were 1.84 (1.54–2.14), 2.64 (2.20–3.08), 3.98 (3.66–4.30), and 4.78 (4.53–5.03) μg/mL for n = 1, 2, 3, and 4, respectively. The slope steepness for the relationship of the C(e) versus sedative response to propofol (95% confidence interval) was 5.76 (4.00–7.52). CONCLUSIONS: We quantified the pharmacodynamic relationship between the C(e) of propofol and UMSS score, and this finding may be helpful to predict the sedation score at the target C(e) of propofol in children. TRIAL REGISTRATION: http://www.clinicaltrials.gov (No.: NCT03195686, Date of registration: 22/06/2017).