Effect of Anesthesia on the Developing Brain: Infant and Fetus

Abstract

recent human clinical anesthetic neurotoxicity trials. Finally, the rationale for studying dexmedetomidine as a potential neuroprotectant agent in anesthetic neurotoxicity will be reviewed along with study design for two human clinical trials involving dexmedetomidine.

Analgesics and Sedatives in Critically Ill Newborns and Infants: The Impact on Long‐Term Neurodevelopment

“…Commonly used sedatives such as midazolam and propofol bind either to gamma‐aminobutyric acid or NMDA receptors. The gamma‐aminobutyric acid and NDMA receptor systems are crucial for neuronal connection and communication in the developing brain and, if unavailable, lead to neuroapoptosis . These agents have been suggested to disrupt memory formation through its effects on the hippocampus .…”

“…In neonatal pain management, the ultimate goal is to achieve adequate pain management with minimal short‐ and long‐term side effects. The search for the lowest, most effective exposure to analgosedatives becomes even more relevant when taking into account their potential effect on long‐term neurocognitive outcome . For both new compounds and for the already used drugs, dose finding studies (phase 2) can be very instructive before conducting phase 3 efficacy and safety trials .…”

“…In the hippocampus, NMDA receptors are highly involved in long‐term potentiation, a system of persistent strengthening of synapses following high levels of stimulation, that results in the ability to form memories . If these NMDA receptors become occupied due to the presence of, for instance, midazolam, memory formation will be disrupted …”

“…As the majority of infants admitted to neonatal or pediatric intensive care units now survive to discharge, this is of major concern. Although there may be long‐term effects of anesthetic agents on the brain as well, this has been extensively described and reviewed in the past few years due to a recent Food and Drug Administration warning about its use in children younger than 3 years, and is therefore beyond the scope of the current review …”

A systematic review and narrative synthesis on the histological and neurobehavioral long‐term effects of dexmedetomidine

“…Dexmedetomidine, a highly selective alpha‐2 adrenoceptor agonist, is a sedative with analgesic sparing properties. Therefore, it has been suggested as an alternative nontoxic sedative drug . It is already clinically widely used as a sedative in adults and increasingly used in pediatric health care for sedation .…”