Abstract
BackgroundContinuous infusion of propofol has been used to achieve sedation in children. However, the relationship between the effect-site concentration (Ce) of propofol and sedation scale has not been previously examined. The objective of this study was to investigate the relationship between the Ce of propofol and the University of Michigan Sedation Scale (UMSS) score in children with population pharmacodynamic modeling.MethodsA 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 Ce of propofol during the induction of anesthesia. The pharmacodynamic relationship between the Ce of propofol and UMSS score was analyzed by logistic regression with nonlinear mixed-effect modeling.ResultsThe estimated Ce50 (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 Ce versus sedative response to propofol (95% confidence interval) was 5.76 (4.00–7.52).ConclusionsWe quantified the pharmacodynamic relationship between the Ce of propofol and UMSS score, and this finding may be helpful to predict the sedation score at the target Ce of propofol in children.Trial registrationhttp://www.clinicaltrials.gov (No.: NCT03195686, Date of registration: 22/06/2017).
Highlights
Continuous infusion of propofol has been used to achieve sedation in children
At a given University of Michigan Sedation Scale (UMSS) score, the Ce of propofol varied between individuals
This study was the first to quantify the relationship between Ce of propofol and the sedation probability in children according to the UMSS score using the pharmacodynamic model
Summary
Continuous infusion of propofol has been used to achieve sedation in children. The objective of this study was to investigate the relationship between the Ce of propofol and the University of Michigan Sedation Scale (UMSS) score in children with population pharmacodynamic modeling. Continuous infusion of propofol should be used [14, 15]. Several studies have investigated the manual infusion dosage required to achieve sedation in children [7, 14, 15]. Manual infusion of propofol guided by clinical assessment of the sedation scale is associated with an increased risk of overdosage or underdosage when compared to that with target-controlled infusion (TCI) [8,9,10]. Hypotension, bradycardia, apnea, airway obstruction, and delayed recovery are associated with overdosage of propofol [11, 17, 18] while insufficient concentrations of propofol can result in awakeness, sympathetic stimulation, and unsatisfactory procedural condition [10, 11]
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