There are no validated propofol infusion regimens in neonates and infants. Existing pharmacokinetic pharmacodynamic (PKPD) models do not include data from babies under the age of 1 year (1) making dosing in this population empirical, largely based on recommendations from Steur et al (2).
Steur and colleagues recommend a bolus dose between 3-5 mg·kg-1 followed by infusion rates unique for age bands (0-3 months, 3-6 months, 6-9 months, 9-12 months and 1-3 years) and these recommendations were obtained by adapting the adult dosage scheme to neonates and infants. The number of propofol boluses and the time from administration to awakening were used as criteria to adjust the dosage scheme, rather than any pharmacokinetic knowledge (2). The recommended bolus dose of propofol is high for this group; known to have immature clearance pathways and smaller distribution volumes, and the resulting concentrations achieved with these doses are unknown.
A PKPD model for propofol target controlled infusions (the Eleveld model) was developed using pooled data from 1033 subjects with ages ranging from 27 weeks post menstrual age (PMA) to 88 years, and included a maturation model to account for changes in clearance with age (3).
This model was used to simulate expected plasma concentrations based on dosing regimens proposed by Steur et al in 10 children aged 37 weeks PMA – 2 years. Patient demographics (age, height, weight and normal fat mass) were obtained from an existing dataset (4). Simulations were performed in NONMEM (NONMEM 7.4.1, Icon Development Solutions, USA) with 1000 replications and 95% confidence intervals constructed.
Simulated concentrations are interpreted in the context of a target propofol concentration of 3 µg·ml-1; associated with an adequate depth of anaesthesia (5). Proposed changes to dosing regimens are given based on the Eleveld model. This is a work in progress.
- Hara M, Masui K, Eleveld DJ, Struys M, Uchida O. Predictive performance of eleven pharmacokinetic models for propofol infusion in children for long-duration anaesthesia. Br J Anaesth. 2017;118(3):415-23.
- Steur RJ, Perez RS, De Lange JJ. Dosage scheme for propofol in children under 3 years of age. Paediatr Anaesth. 2004;14(6):462-7.
- Eleveld D, Colin P, Absalom A, Struys M. Pharmacokinetic–pharmacodynamic model for propofol for broad application in anaesthesia and sedation. British journal of anaesthesia. 2018;120(5):942-59.
- Anderson B, Holford N. Evaluation of a morphine maturation model for the prediction of morphine clearance in children. Br J Clin Pharmacol. 2011;72(3):518-20; author reply 21-3.
- McFarlan CS, Anderson BJ, Short TG. The use of propofol infusions in paediatric anaesthesia: a practical guide. Pediatric Anesthesia. 1999;9(3):209-16.