A Manual Propofol Infusion Regimen for Neonates and Infants

Abstract

Abstract Aim Manual propofol infusion regimens for neonates and infants have been determined from clinical observations in children under the age of 3 years undergoing anesthesia. We assessed the performance of these regimens using reported age-specific pharmacokinetic parameters for propofol. Where performance was poor, we propose alternative dosing regimens. Method Simulations using a reported general purpose pharmacokinetic propofol model were used to predict propofol blood plasma concentrations during manual infusion regimens recommended for children 0-3 years. Simulated steady state concentrations were 6-8 ?g.mL?1 in the first 30 min that were not sustained during 100 min infusions. Pooled clinical data (n=161, 1902 plasma concentrations) were used to determine an alternative pharmacokinetic parameter set for propofol using non-linear mixed effects models. A new manual infusion regimen for propofol that achieves a steady-state concentration of 3 ?g.mL?1 was determined using a heuristic approach. Results A manual dosing regimen predicted to achieve steady state plasma concentration of 3 ?g.mL?1 comprised a loading dose of 2 mg.kg?1 followed by an infusion rate of 9 mg.kg?1.h?1 for the first 15 min, 7 mg.kg?1.h?1 from 15 to 30 min, 6 mg.kg?1.h?1 from 30 to 60 min, 5 mg.kg?1.h?1 from 1 to 2 hours in neonates (38-44 weeks postmenstrual age). Dose increased with age in those aged 1-2 years with a loading dose of 2.5 mg.kg?1 followed by an infusion rate of 13 mg.kg?1.h?1 for the first 15 min, 12 mg.kg?1.h?1 from 15 to 30 min, 11 mg.kg?1.h?1 from 30 to 60 min, 10 mg.kg?1.h?1 from 1 to 2 hours. Conclusion Propofol clearance increases throughout infancy to reach 92% that reported in adults (1.93 L.min.70kg?1) by 6 months postnatal age and infusion regimens should reflect clearance maturation and be cognisant of adverse effects from concentrations greater than the target plasma concentration. Predicted concentrations using a published general purpose pharmacokinetic propofol model were similar to those determined using a new parameter set using richer neonatal and infant data. This article is protected by copyright. All rights reserved.