Do we really know the pharmacodynamics of anaesthetics used in newborns, infants and children? A review of the experimental and clinical data on neurodegeneration

Abstract

The practices of anaesthesiology and intensive therapy are difficult to imagine without sedation or general anaesthesia, regardless of whether the patient is a newborn, baby, child or adult. The relevant concerns for children are distinct from those for adults, primarily due to the effects of anatomical, physiological and pharmacokinetic-pharmacodynamic (PK/PD) differences, which become increasingly important in the brains of children as they develop. The process of central nervous system maturation in humans lasts for years, but its greatest activity (myelination and synaptogenesis) occurs during the fetal period and the first two years of life. Many experimental studies have demonstrated that exposure to anaesthetic drugs during this period can induce neurodegenerative changes in the central nervous systems of animals. The extrapolation of these results directly to humans must be performed with great caution, but anaesthesiologists around the world must begin to debate the safety of general anaesthesia in humans. Prospective trials should continue being carried out, and anaesthesia and surgery, delayed if possible among the smallest patients. The simultaneous use of different anaesthetics with the same potential neurotoxicities should also be avoided, potentially in favour of regional anaesthesia techniques, in this group of patients.