Size, myths and the clinical pharmacokinetics of analgesia in paediatric patients

In the paediatric population, developmental changes can be predicted by age and are independent of size, which is predicted by bodyweight. Size is commonly standardised using either the per kilogram or the body surface area models. A great many physiological-, structural-and time-related variables scale predictably within and between species with weight exponents of 0.75, 1 and 0.25, respectively. Use of the per kilogram size model has led to the misconception that children have an enhanced capacity to metabolise drugs because of their relatively large liver size or increased hepatic blood flow. This is not necessarily the case. For example, the clearance of opioids often approaches adult rates within the first few months of life when an allometric 3/4 power model is used to scale for size. Age-related changes in physiological processes, such as respiration and cardiac output, disappear with appropriate size models. Size is an important, but little recognised, component in the speed of onset of drugs effects and uptake of inhalational anaesthetic agents. Size models cannot be reliably used to predict dose regimens for children from schedules established for adult patients. Dosage regimens are dependent on clearance and volume of distribution as well as pharmacodynamic factors, which change with age. The age-dependent pharmacodynamic changes described for some opioids in the very young have not yet been completely disentangled from age-related pharmacokinetic changes. When bodyweight is standardised and disentangled from age, developmental changes can be understood more clearly. The future investigation of drugs used in paediatric practice must also include an appropriate size model in order to differentiate age-related factors from size-related factors.