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- W989869345 abstract "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. How General Anesthesia Works According to the 2004 National Hospital Discharge Survey, approximately three million children in the United States undergo surgical procedures that require general anesthesia. 26 This does not include children that require general anesthesia for nonsurgical purposes such as dental procedures or imaging studies. A large portion of these children are infants when they are first exposed to general anesthesia. This fact is concerning considering that many general anesthetics exhibit neurotoxicity in infant animals (including non-human primates). Furthermore, retrospective studies demonstrate that children requiring surgery as infants have lower cognitive performance than children who did not require surgery. 20–22,24,25 Unfortunately, many have criticized this data claiming that these studies could be irrelevant due to confounding factors. The concern for the long-term neurological effects of general anesthesia on infants prompted the FDA in 2007 to look into the data concerning general anesthesia’s neurotoxicity. 26 The FDA determined that no changes could be made to which general anesthetics are administered to infants based on current evidence. 26,27 However, they urged that more comprehensive and conclusive clinical studies be conducted promptly to determine which general anesthetics were neurotoxic to infants or children. 26,27 The FDA also recommended that purely elective surgery be deferred to after 6 months of age at a minimum. 26,27 Clinical studies in infants are crucial considering how long the critical period of neurological development lasts. General anesthetics have been shown to have the most severe detrimental effects on neurological development in animals during critical periods known as synaptogenesis. 9,10,28 The length of synaptogenesis in humans lasts from approximately the second trimester of pregnancy to three" @default.
- W989869345 created "2016-06-24" @default.
- W989869345 creator A5056587082 @default.
- W989869345 date "2015-01-01" @default.
- W989869345 modified "2023-09-27" @default.
- W989869345 title "Certain General Anesthetics Used in Pediatrics Hinder Neurological Development in Infants" @default.
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