Does general anesthesia affect neurodevelopment in infants and children?

Abstract

General anesthesia has been unequivocally linked to abnormal development of the central nervous system, leading to neurocognitive impairments in laboratory models. In vitro and in vivo studies have consistently shown that exposure to GABA agonists (eg, volatile anesthetics, midazolam, and propofol) or NMDA antagonists (eg, ketamine, isoflurane, and nitrous oxide) produces dose dependent and developmental age dependent effects on various neuronal transmission systems. Exposure to these drugs increases neuronal cell death in juvenile animals including rats, mice, and non-human primates. The possibility of anesthetic induced neurotoxicity occurring in children has led to concerns about the safety of pediatric anesthesia. A spectrum of behavioral changes has been documented after general anesthetic exposure in young children, including emergence delirium, which may be evidence of toxicity. Most clinical studies are retrospective; specifics about medications or monitoring are unavailable and many of the outcomes may not be sensitive to detect small neurocognitive deficits. Some of these retrospective studies have shown an association between anesthesia exposure at a young age and neurocognitive deficits, but others have not. Practitioners and families should be reassured that although general anesthetics have the potential to induce neurotoxicity, very little clinical evidence exists to support this.

The Use of Bispectral Index Monitoring Does Not Change Intraoperative Exposure to Volatile Anesthetics in Children

“…There is considerable interest and some concern over the potential risk of general anesthesia, volatile anesthetics in particular, on the developing brain [1][2][3][4]. This potential for neurocognitive effects led the Food and Drug Administration (FDA) to release a Safety Statement in 2017, approving label changes for general anesthetics in young children.…”

A Cross-Sectional Analysis of Community Water Fluoridation and Prevalence of Pediatric Dental Surgery Among Medicaid Enrollees

“…A preponderance of basic science and animal model studies [43][44][45][46] have demonstrated the neurotoxic and neurological effects of commonly used medications for moderate sedation and general anesthesia. Ongoing clinical trials 21,25 have not supported an association between single anesthetic exposure and general intelligence or learning, but there is evidence suggesting that multiple exposures may decrease neuropsychological domains affecting executive functioning. 25,47 The US Food and Drug Administration approved a label change regarding possible neurotoxic effects of general anesthetic and sedation medications in children younger than 3 years, warning that "exposure to these medicines for lengthy periods of time or over multiple surgeries or procedures may negatively affect brain development in children younger than 3 years."…”

“…Ongoing clinical trials 21,25 have not supported an association between single anesthetic exposure and general intelligence or learning, but there is evidence suggesting that multiple exposures may decrease neuropsychological domains affecting executive functioning. 25,47 The US Food and Drug Administration approved a label change regarding possible neurotoxic effects of general anesthetic and sedation medications in children younger than 3 years, warning that "exposure to these medicines for lengthy periods of time or over multiple surgeries or procedures may negatively affect brain development in children younger than 3 years." 20 Beyond potential adverse clinical outcomes, reducing dental surgical procedures has immediate financial implications for health care systems.…”

Propofol Exposure Disturbs the Differentiation of Rodent Neural Stem Cells via an miR-124-3p/Sp1/Cdkn1b Axis

“…However, propofol is still an off-label choice in most clinical pediatric practices (Chidambaran et al, 2015). The current dilemma is that there is a lack of evidence to support the safe use of propofol and there are a growing number of pre-clinical studies attributing neurotoxicity and neurogenic impairment to propofol (Krzisch et al, 2013;Bosnjak et al, 2016;McCann and Soriano, 2019).…”