P32
A SIMULATION OF PROPOFOL TARGET CONTROLLED INFUSION IN IMMATURE INFANTS
B. O. Atandi, P. Arnold
Alder Hey NHS Foundation Trust, UK
Introduction and Aims
Eleveld et. al described a pharmacokinetic-pharmacodynamic model for propofol target controlled infusion (TCI) applicable to a wide population. This is now available in commercial TCI pumps[1]. The pump available in our hospital (Alaris™ neXus) limits the minimum age to 6 months and omits input of gestational age[2]. Nonetheless, the authors are aware of use of these pumps in this age group. The Eleveld model assumes allometric scaling of size and contains two sigmoidal equations adjusting for maturity. We sought, by simulation, to examine the impact of pharmacokinetic differences in younger infants using pumps set at an age of 6 months.
Methods
The study was a computer simulation, without data from real patients. Analysis was conducted in the R computer language (Version 2023.12.1) using the TCI package[3]. We validated the simulation with the neXus TCI pump. Infusion rates were determined by Eleveld effect site TCI for a 6-month-old boy weighing 3.5kg, height 50cm, born at 40 weeks gestation and not receiving opioids. A concentration of 3μg/ml was targeted for 120 minutes, and expected effect site concentration calculated at 10 second intervals for infants of 3 months, 1 month, 2 weeks and newborn. All other patient characteristics were identical. Additionally, pharmacokinetic parameters were calculated (manually and within the package) with inter-patient variability to better understand variations with age.
Results
The model showed good agreement with similar infusion rates to the TCI pump. Figure 1 demonstrates that in infants below the lower age limit of the pump, propofol accumulates gradually to steady state beyond that targeted by the pump. This effect becomes greater and will take longer to reach steady state in younger infants. The greatest difference in pharmacokinetic parameters is in elimination clearance with expected values (25th to 75th quantiles) of; 0.19(0.13-0.26) l/min at 6 months, 0.17(0.12-0.24) at 3 months, 0.11(0.081-0.16) at 1 month, 0.093(0.066-0.13) at 2 weeks, and 0.071(0.05-0.1) in newborns.
Conclusions
If Eleveld TCI pumps are used in infants below 6 months caution is required. At 3 months age the demonstrated effect is small and within expected inter-patient variation. In newborns the effect site concentration would still be rising at 2 hours, reaching approximately twice the targeted value. These differences largely relate to differences in elimination clearance. There is little overlap in expected clearance between newborns and 6-month-olds. In practice all anaesthetics are titrated to patient response, but propofol accumulation should be anticipated in younger infants unless these pumps are modified for immaturity. A limitation is that simulation cannot replace clinical data, our simulation is based on Eleveld modelling, assuming its correctness at these ages. Ultimately, ‘all models are wrong, but some are more useful than others’.
References:
- Eleveld DJ, Colin P, Absalom AR, Struys MMRF. Pharmacokinetic-pharmacodynamic model for propofol for broad application in anaesthesia and sedation. Br J Anaesth. 2018 May;120(5):942-959. doi: 10.1016/j.bja.2018.01.018.
- BD. BD Alaris™ neXus PK Specification sheet. https://www.bd.com/documents/international/brochures/infusion/BD-48755-BD-Alaris-neXus-PK-spec.pdf [Accessed 25th Jan 2024].
- CRAN. Introduction to tci package. https://cran.r-project.org/web/packages/tci/vignettes/overview.html [Accessed 25th Nov 2023].