A manual propofol infusion regimen for neonates and infants.

Abstract

Manual propofol infusion regimens for neonates and infants have been determined from clinical observations in children under the age of 3years 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. Simulations using a reported general purpose pharmacokinetic propofol model were used to predict propofol blood plasma concentrations during manual infusion regimens recommended for children 0-3years. Simulated steady state concentrations were 6-8µg.mL-1 in the first 30minutes that were not sustained during 100minutes infusions. Pooled clinical data (n=161, 1902 plasma concentrations) were used to determine an alternative pharmacokinetic parameter set for propofol using nonlinear mixed effects models. A new manual infusion regimen for propofol that achieves a steady-state concentration of 3µg.mL-1 was determined using a heuristic approach. A manual dosing regimen predicted to achieve steady-state plasma concentration of 3µg.mL-1 comprised a loading dose of 2mg.kg-1 followed by an infusion rate of 9mg.kg-1 .h-1 for the first 15minutes, 7mg.kg-1 .h-1 from 15 to 30minutes, 6mg.kg-1 .h-1 from 30 to 60minutes, 5mg.kg-1 .h-1 from 1 to 2hours in neonates (38-44weeks postmenstrual age). Dose increased with age in those aged 1-2years with a loading dose of 2.5mg.kg-1 followed by an infusion rate of 13mg.kg-1 .h-1 for the first 15minutes, 12mg.kg-1 .h-1 from 15 to 30minutes, 11mg.kg-1 .h-1 from 30 to 60minutes, and 10mg.kg-1 .h-1 from 1 to 2hours. Propofol clearance increases throughout infancy to reach 92% that reported in adults (1.93L.min.70kg-1 ) by 6months postnatal age and infusion regimens should reflect clearance maturation and be cognizant 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.