Date of Award


Document Type


Primary Advisor

Dr. Jeremy Day-Storms


General anesthetics act by either blocking N-methyl-d-aspartate (NMDA) receptors or over stimulating γ-aminobutyric acid (GABA) receptors.1–3 The actions of these receptors are responsible for the anesthetized state and are also crucial in the neurological development of infants.2,4–8 Animal studies, although limited, provide vital information about general anesthesia’s neurotoxicity its hindrance of neurological development. Exposure to general anesthesia can severely hinder proper neuronal migration, synaptogenesis, and can drastically increase neuronal apoptosis in infant animals.9–16 General anesthetics are more neurotoxic to infant animals in combination compared to individually.10,16,17 Additionally, multiple exposures to general anesthesia tend to have compounding deleterious effects on neurological development in infant animals.12 It is likely that repeated exposure and combinational exposure to general anesthetics are the most detrimental to neurological development. Many retrospective studies on human infants show a correlation between exposure to general anesthesia and an increased risk of neurodevelopment disorders.18–25 However, these studies are statistically limited due to confounding factors. These confounding factors are the reason direct evidence of the neurotoxic effects of general anesthetics has been so elusive. In vitro human stem cell models provide an ethical alternative to clinical studies. However, clinical trials are necessary and are the most promising methods for obtaining direct evidence of the deleterious effects of general anesthesia on the developing human brain. Different methods used in clinical trials on infants help to minimalize ethical dilemmas, increase recruitment rates, and maximize safety and expediency. Specifically, this paper will evaluate the efficacy and safety of different methods used in clinical trials and will propose how clinical trials can be designed for future studies.