Pediatric models for adult target-controlled infusion pumps

Area of Science:

• Pharmacology
• Pediatric Anesthesia
• Drug Delivery Systems

Background:

• Current target-controlled infusion (TCI) pumps are inadequate for pediatric patients, especially those under five years old.
• Pediatric growth and development significantly impact drug clearance (CL) and volume of distribution (V), affecting initial dosing and infusion rates.
• Key covariates like size, age, and organ function contribute to pharmacokinetic variability in children.

Purpose of the Study:

• To address the limitations of TCI pumps in pediatric anesthesia.
• To explore the application of allometric scaling and maturation models for pediatric drug dosing.
• To highlight the need for integrated pharmacokinetic and pharmacodynamic data for safe TCI use in children.

Main Methods:

• Utilizing allometric (3/4) power model to standardize clearance for size.
• Applying maturation models, such as the sigmoid Emax or Hill model, to account for developmental changes.
• Analyzing the influence of organ function, particularly in neonates and infants post-cardiac surgery.

Main Results:

• Allometric scaling is effective for drugs like remifentanil but insufficient alone for neonates and infants.
• Maturation models, exemplified by propofol with specific parameters (mature CL, TM(50), Hill coefficient), are necessary for accurate pediatric pharmacokinetic prediction.
• Propofol clearance is notably reduced in neonates and infants after cardiac surgery, underscoring the role of organ function.

Conclusions:

• Pharmacokinetic models for pediatric TCI require integration of size, age-related maturation, and organ function.
• While pharmacokinetics are programmable, pharmacodynamic measures in children remain poorly defined, hindering optimal TCI use.
• Accurate pharmacokinetic and pharmacodynamic data are essential for the safe and effective application of TCI pumps in pediatric anesthesia.