Created May 21, 2015, last updated 4 months ago.
Collection: 18, Score: 1060, Trend score: 0, Read count: 1061, Articles count: 11, Created: 2015-05-21 04:21:37 UTC. Updated: 2021-02-15 23:29:45 UTC.
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Anaesthesia-related neurotoxicity in the developing brain has been observed in animal models and suggested by observational human trials. Conclusive, quality evidence directing significant practice change is however lacking. Anaesthetists should be aware of the current evidence and future directions of research into this important area.summary
Retrospective studies show that a single anesthesia exposure before age 3 may undermine language acquisition and abstract reasoning, and exposure to two or more anesthetics before age 2 almost doubles the risk of attention-deficit hyperactivity disorder, although in both cases causality has not yet been established.summary
A multitude of animal studies have shown that virtually all general anesthetics used in clinical practice possibly during a vulnerable period of brain development (i.e., brain growth spurt, peak of synaptogenesis) may lead to neurodegeneration (particularly apoptosis) and abnormal synaptic development with functional deficits in learning and behavior later in life. Initial studies were mainly performed in immature rodent pups, but more recent studies have included nonhumans primates (rhesus monkeys). Given the number of neonates, infants, and young children anesthetized annually worldwide, these findings could have significant public health implications. ⋯ Multiple anesthetic and surgical exposures on the other hand are different. But there may be other reasons for this than merely the anesthetics. Currently, there is no need to change current anesthetic clinical practice or to postpone or cancel truly urgent surgeries in young children.
A great deal of concern has recently arisen regarding the safety of anaesthesia in infants and children. There is mounting and convincing preclinical evidence in rodents and non-human primates that anaesthetics in common clinical use are neurotoxic to the developing brain in vitro and cause long-term neurobehavioural abnormalities in vivo. An estimated 6 million children (including 1.5 million infants) undergo surgery and anaesthesia each year in the USA alone, so the clinical relevance of anaesthetic neurotoxicity is an urgent matter of public health. ⋯ The aim of this study is to examine the neurodevelopmental effects of exposure to general anaesthesia during inguinal hernia surgery before 36 months of age. Another large-scale study is the GAS study, which will compare the neurodevelopmental outcome between two anaesthetic techniques, general sevoflurane anaesthesia and regional anaesthesia, in infants undergoing inguinal hernia repair. These study results should contribute significant information related to anaesthetic neurotoxicity in children.
The anaesthetic dose causing neurotoxicity in animals has been evaluated, but the relationship between duration of volatile anaesthetic (VA) exposure and neurodevelopment in children remains unclear. ⋯ Children with VA exposures ≤35 min did not differ from unexposed children, but those with exposures >35 min had lower total and expressive language scores. It remains unclear if this is a dose-response relationship, or if children requiring longer exposures for longer surgeries have other clinical reasons for lower scores.
Few studies of how exposure of children to anesthesia may affect neurodevelopment employ comprehensive neuropsychological assessments. This study tested the hypothesis that exposure to multiple, but not single, procedures requiring anesthesia before age 3 yr is associated with adverse neurodevelopmental outcomes. ⋯ Anesthesia exposure before age 3 yr was not associated with deficits in the primary outcome of general intelligence. Although secondary outcomes must be interpreted cautiously, they suggest the hypothesis that multiple, but not single, exposures are associated with a pattern of changes in specific neuropsychological domains that is associated with behavioral and learning difficulties.
Although there is reasonable confidence that a single general anaesthetic before three years of age has no consequences for intelligence development, there is an association between multiple exposures and learning and behavioural difficulties, possibly including ADHD. Animal studies have demonstrated ADHD-like changes in juvenile rats exposed to general anaesthetics.
There is a plausible physiological explanation for how general anaesthesia may induce ADHD, involving disruption of the prefrontal cortex and basal ganglia via dopaminergic, glutaminergic and neutrophic factor mechanisms.
Nonetheless, evidence to date linking general anaesthetic exposure in young children and ADHD development is far from conclusive and – as with many areas of practice – requires further research.summary
Randomized Controlled Trial Multicenter Study
Preclinical data suggest that general anaesthetics affect brain development. There is mixed evidence from cohort studies that young children exposed to anaesthesia can have an increased risk of poor neurodevelopmental outcome. We aimed to establish whether general anaesthesia in infancy has any effect on neurodevelopmental outcome. Here we report the secondary outcome of neurodevelopmental outcome at 2 years of age in the General Anaesthesia compared to Spinal anaesthesia (GAS) trial. ⋯ Australia National Health and Medical Research Council (NHMRC), Health Technologies Assessment-National Institute for Health Research UK, National Institutes of Health, Food and Drug Administration, Australian and New Zealand College of Anaesthetists, Murdoch Childrens Research Institute, Canadian Institute of Health Research, Canadian Anesthesiologists' Society, Pfizer Canada, Italian Ministry of Heath, Fonds NutsOhra, and UK Clinical Research Network (UKCRN).
Neurodegeneration has been reported in young animals after exposure to all commonly used general anesthetic agents. The brain may be particularly vulnerable to anesthetic toxicity during peak synaptogenesis (in gestation and infancy). Human studies of long-term neurodevelopmental outcome following general anesthesia in early childhood report contradictory findings. ⋯ We discuss potential solutions to these challenges. Further adequately powered, multicenter, prospective randomized controlled trials of anesthetic-induced neurotoxicity in children are required. However, we believe that the inherent methodological challenges of studying anesthetic-induced neurotoxicity necessitate the parallel use of well-designed observational cohort studies.
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