Consequences of General Anesthesia in Infancy on Behavior and Brain Structure.
Journal
Anesthesia and analgesia
ISSN: 1526-7598
Titre abrégé: Anesth Analg
Pays: United States
ID NLM: 1310650
Informations de publication
Date de publication:
01 02 2023
01 02 2023
Historique:
entrez:
13
1
2023
pubmed:
14
1
2023
medline:
18
1
2023
Statut:
ppublish
Résumé
One in 7 children will need general anesthesia (GA) before the age of 3. Brain toxicity of anesthetics is controversial. Our objective was to clarify whether exposure of GA to the developing brain could lead to lasting behavioral and structural brain changes. A first study was performed in mice. The behaviors (fear conditioning, Y-maze, and actimetry) and brain anatomy (high-resolution magnetic resonance imaging) of 6- to 8-week-old Swiss mice exposed or not exposed to GA from 4 to 10 days old were evaluated. A second study was a complementary analysis from the preexisting APprentissages EXécutifs et cerveau chez les enfants d'âge scolaire (APEX) cohort to assess the replicability of our data in humans. The behaviors (behavior rating inventory of executive function, emotional control, and working memory score, Backward Digit Span, and Raven 36) and brain anatomy (high-resolution magnetic resonance imaging) were compared in 102 children 9 to 10 years of age exposed or not exposed to a single GA (surgery) during infancy. The animal study revealed chronic exacerbated fear behavior in the adult mice (95% confidence interval [CI], 4-80; P = .03) exposed to postnatal GA; this was associated with an 11% (95% CI, 7.5-14.5) reduction of the periaqueductal gray matter (P = .046). The study in humans suggested lower emotional control (95% CI, 0.33-9.10; P = .06) and a 6.1% (95% CI, 4.3-7.8) reduction in the posterior part of the right inferior frontal gyrus (P = .019) in the children who had been exposed to a single GA procedure. The preclinical and clinical findings of these independent studies suggest lasting effects of early life exposure to anesthetics on later emotional control behaviors and brain structures.
Sections du résumé
BACKGROUND
One in 7 children will need general anesthesia (GA) before the age of 3. Brain toxicity of anesthetics is controversial. Our objective was to clarify whether exposure of GA to the developing brain could lead to lasting behavioral and structural brain changes.
METHODS
A first study was performed in mice. The behaviors (fear conditioning, Y-maze, and actimetry) and brain anatomy (high-resolution magnetic resonance imaging) of 6- to 8-week-old Swiss mice exposed or not exposed to GA from 4 to 10 days old were evaluated. A second study was a complementary analysis from the preexisting APprentissages EXécutifs et cerveau chez les enfants d'âge scolaire (APEX) cohort to assess the replicability of our data in humans. The behaviors (behavior rating inventory of executive function, emotional control, and working memory score, Backward Digit Span, and Raven 36) and brain anatomy (high-resolution magnetic resonance imaging) were compared in 102 children 9 to 10 years of age exposed or not exposed to a single GA (surgery) during infancy.
RESULTS
The animal study revealed chronic exacerbated fear behavior in the adult mice (95% confidence interval [CI], 4-80; P = .03) exposed to postnatal GA; this was associated with an 11% (95% CI, 7.5-14.5) reduction of the periaqueductal gray matter (P = .046). The study in humans suggested lower emotional control (95% CI, 0.33-9.10; P = .06) and a 6.1% (95% CI, 4.3-7.8) reduction in the posterior part of the right inferior frontal gyrus (P = .019) in the children who had been exposed to a single GA procedure.
CONCLUSIONS
The preclinical and clinical findings of these independent studies suggest lasting effects of early life exposure to anesthetics on later emotional control behaviors and brain structures.
Identifiants
pubmed: 36638508
doi: 10.1213/ANE.0000000000006233
pii: 00000539-202302000-00010
doi:
Substances chimiques
Anesthetics
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
240-250Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 International Anesthesia Research Society.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
Références
Jevtovic-Todorovic V. Monkey business: the importance of mounting behavioural evidence for anaesthesia-induced developmental neurotoxicity. Br J Anaesth. 2018;120:617–619.
Jevtovic-Todorovic V. Exposure of developing brain to general anesthesia: what is the animal evidence? Anesthesiology. 2018;128:832–839.
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.
McCann ME, de Graaff JC, Dorris L, et al.; GAS Consortium. 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.
Russell LE, Dalgleish HWP, Nutbrown R, et al. All-optical interrogation of neural circuits in behaving mice. Nat Protoc. 2022;17:1579–1620.
Poirel N, Borst G, Simon G, et al. Number conservation is related to children’s prefrontal inhibitory control: an fMRI study of a Piagetian task. PLoS One. 2012;7:e40802.
Mannara F, Radosevic M, Planagumà J, et al. Allosteric modulation of NMDA receptors prevents the antibody effects of patients with anti-NMDAR encephalitis. Brain. 2020;143:2709–2720.
Chatterjee S, Angelakos CC, Bahl E, et al. The CBP KIX domain regulates long-term memory and circadian activity. BMC Biol. 2020;18:155.
Dellu F, Contarino A, Simon H, et al. Genetic differences in response to novelty and spatial memory using a two-trial recognition task in mice. Neurobiol Learn Mem. 2000;73:31–48.
Chung MK, Worsley KJ, Paus T, et al. A unified statistical approach to deformation-based morphometry. Neuroimage. 2001;14:595–606.
Delalande L, Moyon M, Tissier C, et al. Complex and subtle structural changes in prefrontal cortex induced by inhibitory control training from childhood to adolescence. Dev Sci. 2020;23:e12898.
Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia. 1971;9:97–113.
Baron IS. Behavior rating inventory of executive function. Child Neuropsychol. 2000;6:235–238.
Raven J, Raven JC, Court JH. Manual for Raven’s Progressive Matrices and Vocabulary Scales. Oxford Psychologists Press; 1998.
Lemaire C, Moran GR, Swan H. Impact of audio/visual systems on pediatric sedation in magnetic resonance imaging. J Magn Reson Imaging. 2009;30:649–655.
Ashburner J. Computational anatomy with the SPM software. Magn Reson Imaging. 2009;27:1163–1174.
Ashburner J. A fast diffeomorphic image registration algorithm. Neuroimage. 2007;38:95–113.
Rozeske RR, Jercog D, Karalis N, et al. Prefrontal-periaqueductal gray-projecting neurons mediate context fear discrimination. Neuron. 2018;97:898–910.e6.
Ho YC, Lin TB, Hsieh MC, et al. Periaqueductal gray glutamatergic transmission governs chronic stress-induced depression. Neuropsychopharmacology. 2018;43:302–312.
Satomoto M, Sun Z, Adachi YU, et al. Neonatal sevoflurane exposure induces adulthood fear-induced learning disability and decreases glutamatergic neurons in the basolateral amygdala. J Neurosurg Anesthesiol. 2018;30:59–64.
Rosenholm M, Paro E, Antila H, et al. Repeated brief isoflurane anesthesia during early postnatal development produces negligible changes on adult behavior in male mice. PLoS One. 2017;12:e0175258.
Kodama M, Satoh Y, Otsubo Y, et al. Neonatal desflurane exposure induces more robust neuroapoptosis than do isoflurane and sevoflurane and impairs working memory. Anesthesiology. 2011;115:979–991.
Zhang L, Li W, Wang L, et al. Altered functional connectivity of right inferior frontal gyrus subregions in bipolar disorder: a resting state fMRI study. J Affect Disord. 2020;272:58–65.
Luby JL, Barch D, Whalen D, et al. Association between early life adversity and risk for poor emotional and physical health in adolescence: a putative mechanistic neurodevelopmental pathway. JAMA Pediatr. 2017;171:1168–1175.
Ing C, Jackson WM, Zaccariello MJ, et al. Prospectively assessed neurodevelopmental outcomes in studies of anaesthetic neurotoxicity in children: a systematic review and meta-analysis. Br J Anaesth. 2021;126:433–444.
Andropoulos DB, Easley RB, Brady K, et al. Changing expectations for neurological outcomes after the neonatal arterial switch operation. Ann Thorac Surg. 2012;94:1250–1255.
Habre W, Disma N, Virag K, et al.; APRICOT Group of the European Society of Anaesthesiology Clinical Trial Network. Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe. Lancet Respir Med. 2017;5:412–425.
Salvia E, Tissier C, Charron S, et al. The local properties of bold signal fluctuations at rest monitor inhibitory control training in adolescents. Dev Cogn Neurosci. 2019;38:100664.
Backeljauw B, Holland SK, Altaye M, et al. Cognition and brain structure following early childhood surgery with anesthesia. Pediatrics. 2015;136:e1–12.
Qiu J, Shi P, Mao W, et al. Effect of apoptosis in neural stem cells treated with sevoflurane. BMC Anesthesiol. 2015;15:25.
Yin W, Mei L, Sun T, et al. A central amygdala-ventrolateral periaqueductal gray matter pathway for pain in a mouse model of depression-like behavior. Anesthesiology. 2020;132:1175–1196.
Baud O, Saint-Faust M. Neuroinflammation in the developing brain: risk factors, involvement of microglial cells, and implication for early anesthesia. Anesth Analg. 2019;128:718–725.
Zhang X, Liu S, Newport GD, et al. In vivo monitoring of sevoflurane-induced adverse effects in neonatal nonhuman primates using small-animal positron emission tomography. Anesthesiology. 2016;125:133–146.
Apai C, Shah R, Tran K, et al. Anesthesia and the developing brain: a review of sevoflurane-induced neurotoxicity in pediatric populations. Clin Ther. 2021;43:762–778.
Chinn GA, Pearn ML, Vutskits L, et al. Standards for preclinical research and publications in developmental anaesthetic neurotoxicity: expert opinion statement from the SmartTots preclinical working group. Br J Anaesth. 2020;124:585–593.
Blakemore RL, Rieger SW, Vuilleumier P. Negative emotions facilitate isometric force through activation of prefrontal cortex and periaqueductal gray. Neuroimage. 2016;124:627–640.
Deng H, Xiao X, Wang Z. Periaqueductal gray neuronal activities underlie different aspects of defensive behaviors. J Neurosci. 2016;36:7580–7588.
Weiss M, Vutskits L, Hansen TG, et al. Safe anesthesia for every tot—the SAFETOTS initiative. Curr Opin Anaesthesiol. 2015;28:302–307.
Disma N, Veyckemans F, Virag K, et al.; NECTARINE Group of the European Society of Anaesthesiology Clinical Trial Network; Austria; Belgium; Croatia; Czech Republic; Denmark; Estonia; Finland; France; Germany; Greece; Hungary; Ireland; Italy; Latvia; Lithuania; Luxembourg; Malta; Netherlands; Norway; Poland; Portugal; Romania; Serbia; Slovakia; Slovenia; Spain; Switzerland; Turkey; Ukraine; United Kingdom. Morbidity and mortality after anaesthesia in early life: results of the European prospective multicentre observational study, neonate and children audit of anaesthesia practice in Europe (NECTARINE). Br J Anaesth. 2021;126:1157–1172.
Warner DO, Zaccariello MJ, Katusic SK, et al. Neuropsychological and behavioral outcomes after exposure of young children to procedures requiring general anesthesia: the Mayo Anesthesia Safety in Kids (MASK) study. Anesthesiology. 2018;129:89–105.