A manual propofol infusion regimen for neonates and infants

Aims: Manual propofol infusion regimens for neonates and infants have been de‐ termined from clinical observations in children under the age of 3 years undergoing anesthesia. We assessed the performance of these regimens using reported age‐spe‐ cific 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 con‐ centrations 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 heu‐ ristic approach. Results: A manual dosing regimen predicted to achieve steady‐state plasma concen‐ tration 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 re‐ ported 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 con‐ centrations 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.

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