Twenty-five years ago, surgery was commonly performed on awake or paralyzed infants and children without the benefit of analgesics, sedatives, or anesthetics. This practice was justified by a fear that these drugs would increase the risk of adverse surgical outcomes and the belief that infants did not experience pain. Subsequent clinical studies have demonstrated that inadequate sedation, anesthesia, and analgesia may actually increase the risk of adverse postoperative outcomes in infants and children and have led to a paradigm shift such that the use of general anesthetics and analgesics is now routine in the humane practice of pediatric anesthesiology. This does not mean that doing so is without risk or controversy. Seven years after this change, questions began to arise from the laboratory of John Olney, M.D., who was well known for his work on fetal alcohol syndrome, suggesting that exposure to anesthetics and sedatives with mechanisms of action similar to those of alcohol may result in adverse outcomes in neonatal animals. These findings have been replicated in multiple laboratories, using a number of animal species, and demonstrate that prolonged or repeated administration of anesthetics and sedatives to prenatal and neonatal animals is associated with abnormal brain development and an increased risk of cognitive and behavioral abnormalities in later life. In this issue of Anesthesiology, Dr. Jevtovic-Todorovic, a prominent investigator in the field, reviews the basic science literature that served to suggest to the U.S. Food and Drug Administration (FDA; Silver Spring, Maryland) a need for a warning on the use sedatives and anesthetics during pregnancy and early childhood.
- Propofol and Sevoflurane Anesthesia in Early Childhood Do Not Influence Seizure Threshold in Adult Rats.
- Sevoflurane Exposure in the Developing Brain Induces Hyperactivity, Anxiety-Free, and Enhancement of Memory Consolidation in Mice.
- Fentanyl induces autism-like behaviours in mice by hypermethylation of the glutamate receptor gene Grin2b.
- Multiple exposures to sevoflurane across postnatal development may cause cognitive deficits in older age.
- Mitochondria-Related Ferroptosis Drives Cognitive Deficits in Neonatal Mice Following Sevoflurane Administration.