A manual propofol infusion regimen for neonates and infants

Aims: 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.

Methods: 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 µg.mL^-1 in the first 30 minutes that were not sustained during 100 minutes 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 3 µg.mL^-1 was determined using a heuristic approach.

Results: A manual dosing regimen predicted to achieve steady-state plasma concentration of 3 µg.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 minutes, 7 mg.kg^-1 .h^-1 from 15 to 30 minutes, 6 mg.kg^-1 .h^-1 from 30 to 60 minutes, 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 minutes, 12 mg.kg^-1 .h^-1 from 15 to 30 minutes, 11 mg.kg^-1 .h^-1 from 30 to 60 minutes, and 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.70 kg^-1 ) by 6 months 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.