Early exposure to general anaesthesia: considerations for age-related vulnerability and behavioural outcomes

Millions of children undergo general anaesthesia each year during surgery, imaging, and other medical procedures. The potential pathogenic effects of anaesthesia on the developing brain have become increasingly concerning. However, the mechanisms and confounding factors of paediatric anaesthesia toxicity are not well understood, limiting our ability to investigate this subject comprehensively. The timing, duration, and frequency of anaesthesia exposure has been suggested to potentially determine the degree of brain impairment. 1 Robinson EJ Lyne TC Blaise BJ Safety of general anaesthetics on the developing brain: are we there yet?. BJA Open. 2022; 2100012 Summary Full Text Full Text PDF PubMed Google Scholar Notably though, while preclinical studies typically indicate behavioural deficits, human studies present a more variable picture, with some showing these effects 2 Wilder RT Flick RP Sprung J et al. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology. 2009; 110: 796-804 Crossref PubMed Scopus (1182) Google Scholar , 3 Chemaly M El-Rajab MA Ziade FM Naja ZM Effect of one anesthetic exposure on long-term behavioral changes in children. J Clin Anesth. 2014; 26: 551-556 Crossref PubMed Google Scholar and others not. 4 McCann ME de Graaff JC Dorris L et al. Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicentre, randomised, controlled equivalence trial. Lancet. 2019; 393: 664-677 Summary Full Text Full Text PDF PubMed Scopus (441) Google Scholar , 5 Sun LS Li G Miller TL et al. Association between a single general anesthesia exposure before age 36 months and neurocognitive outcomes in later childhood. JAMA. 2016; 315: 2312-2320 Crossref PubMed Google Scholar Therefore, efforts are concentrating on three main points of research in this area: conducting more prospective randomised studies in children to increase and enrich clinical data, finding clear mechanisms at least at the preclinical level, and unifying preclinical and clinical studies to make them comparable. Long-term outcomes of early exposure to repeated general anaesthesia in children with cystic fibrosis (CF-GAIN): a multicentre, open-label, randomised controlled phase 4 trialOur findings suggest that repeated general anaesthesia exposure in young children with cystic fibrosis is not related to functional impairment in attention, intellectual quotient, executive function, or brain structure compared with a group with fewer and shorter cumulative anaesthesia durations. Full-Text PDF