Pediatric models for adult target‐controlled infusion pumps

Abstract

Target-controlled infusion (TCI) pumps currently do not satisfactorily cater for the pediatric population, particularly for those under 5 years. Growth and development are two major aspects of children not readily apparent in adults, and these two aspects influence clearance (CL) and volume of distribution (V). In simple terms, V determines initial dose, and CL determines infusion rate at steady state. Three major covariates (size, age, and organ function) contribute to parameter variability in children. Size can be standardized for clearance in a 70-kg person using the allometric (3/4) power model. Remifentanil, a drug cleared by hydrolysis, can be modeled in all age groups by simple application of this model using a standardized clearance of 2790 ml x min(-1) for a 70-kg person. Allometry alone is insufficient to predict clearance in neonates and infants from adult parameters for most drugs used in anesthesia. The addition of a model describing maturation is required. The sigmoid Emax or Hill model has been found useful for describing this maturation process. Propofol maturation has been described with a mature clearance of 1.83 l x min(-1) x 70 kg(-1), a maturation half-time (TM(50)) of 44 weeks and a Hill coefficient of 4.9. Organ function also affects clearance, and propofol clearance is reduced in neonates and infants after cardiac surgery. Although pharmacokinetics (PK) in children is receiving increasing attention and is eminently programmable into a TCI device, pharmacodynamic (PD) measures in children remain poorly defined, partly because the depth of anesthesia monitoring are inadequate. Both PK and PD are necessary for safe use of TCI pumps.