Aspects fondamentaux de la toxicite éventuelle des drogues anesthésiques

Abstract

Brain development is a complex phenomenon in which several stages of production, maturation, and organization of neural cells in a network succeed each other. Various environmental factors can disrupt these stages. During the last decade, numerous in vitro and in vivo experimental studies in newborn animal models have established the neurotoxic effects of most anesthetic and sedative drugs used in pediatrics. These effects are essentially responsible for neuronal apoptosis and have been associated with learning disorders in adulthood. This neurotoxicity is time-varying: there is a vulnerability period during synaptogenesis. These toxic effects were attributed to agonist properties on GABA receptors or antagonist properties on NMDA receptors, which are characteristics of all implicated anesthetics. Excessive activation of the GABA pathway and/or excessive inhibition of the NMDA pathway activate cellular mechanisms leading to apoptosis. The intensity of neurotoxic effects is dose- and time-exposure-dependent. These numerous experimental data must be interpreted with caution with regard to their validity in humans, mainly because of interspecies differences as well as differences between experimental conditions and clinical practice. Today, these data are insufficient to change our practices, taking into account the indisputable benefits of the use of anesthetics and sedative drugs. However, progress in experimental research will help us identify the safest therapeutic strategies and neuroprotective treatments.