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Postoperative Cognitive Function Following General Anesthesia in Children

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Book cover General Anesthesia Research

Part of the book series: Neuromethods ((NM,volume 150))

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Abstract

Research into the developmental effects of anesthetic use began from the study of the fetal and postnatal effects of maternal alcohol consumption. Broadly speaking, alcohol is an anesthetic of sorts, and its toxicity as such has been firmly established: there is a consensus on the danger of alcohol to children as the warning label on every can of beer reminds us. Furthermore, studies using rodents have largely confirmed the toxicity of anesthetics on the developing brain. Although some human retrospective observational studies have found anesthetics to be toxic while others have not, as mentioned earlier the difficulty of assembling cohorts with matching backgrounds has rendered interpretation of the results difficult. To date, two large-scale human studies have been conducted; the preliminary findings of one of these demonstrated no apparent effect of the short-term use of anesthetics on healthy children. Against this, we have the warning issued by the FDA and based on the results of the animal studies and retrospective observation studies, which applies to all anesthetics and sedatives besides alpha-2 agonists, as previously described: the extended or multiple use of these agents in children younger than 3 years of age or in fetuses during the third trimester may adversely affect brain development. In light of the foregoing information, the clinician is left to ponder the very serious question of which anesthetic procedures to use with pediatric patients. Given the state of our current knowledge, the answer to this question must be to shorten exposure as much as possible and to limit the dosage to strictly appropriate quantities. The prevailing view at present is that short-term exposure of healthy children to anesthetics has no adverse effects on brain development.

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References

  1. Jones KL, Smith DW (1973) Recognition of the fetal alcohol syndrome in early infancy. Lancet 302:999–1001

    Article  CAS  Google Scholar 

  2. Jones KL, Smith DW, Ulleland CN et al (1973) Pattern of malformation in offspring of chronic alcoholic mothers. Lancet 1:1267–1271

    Article  CAS  Google Scholar 

  3. Clarren SK, Smith DW (1978) The fetal alcohol syndrome. N Engl J Med 298:1063–1067

    Article  CAS  Google Scholar 

  4. Dobbing J, Sands J (1979) Comparative aspects of the brain growth spurt. Early Hum Dev 3:79–83

    Article  CAS  Google Scholar 

  5. Rice D, Barone S Jr (2000) Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect 108S:511–533

    Google Scholar 

  6. Ikonomidou C, Bosch F, Miksa M et al (1999) Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 283:70–74

    Article  CAS  Google Scholar 

  7. Ikonomidou C, Bittigau P, Ishimaru MJ et al (2000) Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science 287:1056–1060

    Article  CAS  Google Scholar 

  8. Fredriksson A, Pontén E, Gordh T et al (2007) Neonatal exposure to a combination of N-methyl-D-aspartate and gamma-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits. Anesthesiology 107:427–436

    Article  CAS  Google Scholar 

  9. Hemmings HC Jr, Akabas MH, Goldstein PA et al (2005) Emerging molecular mechanisms of general anesthetic action. Trends Pharmacol Sci 26:503–510

    Article  CAS  Google Scholar 

  10. Paule MG, Li M, Allen RR et al (2011) Ketamine anesthesia during the first week of life can cause long-lasting cognitive deficits in rhesus monkeys. Neurotoxicol Teratol 33:220–230

    Article  CAS  Google Scholar 

  11. Rizzi S, Carter LB, Ori C et al (2008) Clinical anesthesia causes permanent damage to the fetal guinea pig brain. Brain Pathol 18:198–210

    Article  Google Scholar 

  12. Shen X, Dong Y, Xu Z et al (2013) Selective anesthesia-induced neuroinflammation in developing mouse brain and cognitive impairment. Anesthesiology 118:502–515

    Article  CAS  Google Scholar 

  13. Shen X, Liu Y, Xu S et al (2013) Early life exposure to sevoflurane impairs adulthood spatial memory in the rat. Neurotoxicology 39:45–56

    Article  CAS  Google Scholar 

  14. Zou X, Liu F, Zhang X et al (2011) Inhalation anesthetic-induced neuronal damage in the developing rhesus monkey. Neurotoxicol Teratol 33:592–597

    Article  CAS  Google Scholar 

  15. Istaphanous GK, Howard J, Nan X et al (2011) Comparison of the neuroapoptotic properties of equipotent anesthetic concentrations of desflurane, isoflurane, or sevoflurane in neonatal mice. Anesthesiology 114:578–587

    Article  CAS  Google Scholar 

  16. Jevtovic-Todorovic V, Hartman RE, Izumi Y et al (2003) Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 23:876–882

    Article  CAS  Google Scholar 

  17. Rizzi S, Ori C, Jevtovic-Todorovic V (2010) Timing versus duration: Determinants of anesthesia-induced developmental apoptosis in the young mammalian brain. Ann N Y Acad Sci 1199:43–51

    Article  CAS  Google Scholar 

  18. Young C, Jevtovic-Todorovic V, Qin YQ et al (2005) Potential of ketamine and midazolam, individually or in combination, to induce apoptotic neurodegeneration in the infant mouse brain. Br J Pharmacol 146:189–197

    Article  CAS  Google Scholar 

  19. Nikizad H, Yon JH, Carter LB et al (2007) Early exposure to general anesthesia causes significant neuronal deletion in the developing rat brain. Ann N Y Acad Sci 1122:69–82

    Article  CAS  Google Scholar 

  20. Sanders RD, Xu J, Shu Y et al (2008) General anesthetics induce apoptotic neurodegeneration in the neonatal rat spinal cord. Anesth Analg 106:1708–1711

    Article  CAS  Google Scholar 

  21. Straiko MMW, Young C, Cattano D et al (2009) Lithium protects against anesthesia-induced developmental neuroapoptosis. Anesthesiology 110:662–668

    Article  Google Scholar 

  22. Sanders RD, Sun P, Patel S et al (2010) Dexmedetomidine provides cortical neuroprotection: impact on anaesthetic-induced neuroapoptosis in the rat developing brain. Acta Anaesthesiol Scand 54:710–716

    Article  CAS  Google Scholar 

  23. Yon JH, Carter LB, Jevtovic-Todorovic V (2006) Melatonin reduces the severity of anesthesia-induced apoptotic neurodegeneration in the developing rat brain. Neurobiol Dis 21:522–530

    Article  CAS  Google Scholar 

  24. Cattano D, Young C, Olney JW (2008) Sub-anesthetic doses of propofol induce neuroapoptosis in the infant mouse brain. Anesth Analg 106:1712–1714

    Article  CAS  Google Scholar 

  25. Ma D, Williamson P, Januszewski A et al (2007) Xenon mitigates isoflurane-induced neuronal apoptosis in the developing rodent brain. Anesthesiology 106:746–753

    Article  CAS  Google Scholar 

  26. Johnson SA, Young C, Olney JW (2008) Isoflurane-induced neuroapoptosis in the developing brain of non-hypoglycemic mice. J Neurosurg Anesth 20:21–28

    Article  Google Scholar 

  27. Sanders RD, Xu J, Shu Y et al (2009) Dexmedetomidine attenuates isoflurane-induced neurocognitive impairment in neonatal rats. Anesthesiology 110:11077–11085

    Google Scholar 

  28. Zhang X, Xue Z, Sun A (2008) Subclinical concentration of sevoflurane potentiates neuronal apoptosis in the developing C57BL/6 mouse brain. Neurosci Lett 447:109–114

    Article  CAS  Google Scholar 

  29. Cattano D, Williamson P, Fukui K et al (2008) Potential of xenon to induce or to protect against neuroapoptosis in the developing mouse brain. Can J Anesth 55:429–436

    Article  Google Scholar 

  30. Brambrink AM, Evers AS, Avidan MS et al (2010) Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology 112:834–841

    Article  CAS  Google Scholar 

  31. Brambrink AM, Evers AS, Avidan MS et al (2012) Ketamine-induced neuroapoptosis in the fetal and neonatal rhesus macaque brain. Anesthesiology 116:372–384

    Article  CAS  Google Scholar 

  32. Brambrink AM, Back SA, Riddle A et al (2012) Isoflurane-induced apoptosis of oligodendrocytes in the neonatal primate brain. Ann Neurol 72:525–535

    Article  CAS  Google Scholar 

  33. Slikker W Jr, Zou X, Hotchkiss CE et al (2007) Ketamine-induced neuronal cell death in the perinatal rhesus monkey. Toxicol Sci 98:145–158

    Article  CAS  Google Scholar 

  34. Zou X, Patterson TA, Divine RL et al (2009) Prolonged exposure to ketamine increases neurodegeneration in the developing monkey brain. Int J Dev Neurosci 27:727–731

    Article  CAS  Google Scholar 

  35. Fredriksson A, Archer T (2004) Neurobehavioural deficits associated with apoptotic neurodegeneration and vulnerability for ADHD. Neurotox Res 6:435–456

    Article  Google Scholar 

  36. Satomoto M, Satoh Y, Terui K et al (2009) Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice. Anesthesiology 110:628–637

    Article  CAS  Google Scholar 

  37. Stratmann G, Sall JW, May LD et al (2009) Isoflurane differentially affects neurogenesis and long-term neurocognitive function in 60- and 7-day-old rats. Anesthesiology 110:834–848

    Article  CAS  Google Scholar 

  38. Wozniak DF, Hartman RE, Boyle MP et al (2004) Apoptotic neurodegeneration induced by ethanol in neonatal mice is associated with profound learning/memory deficits in juveniles followed by progressive functional recovery in adults. Neurobiol Dis 17:403–414

    Article  CAS  Google Scholar 

  39. Sun Z, Satomoto M, Adachi YU et al (2016) Inhibiting NADPH oxidase protects against long-term memory impairment induced by neonatal sevoflurane exposure in mice. Br J Anaesth 117:80–86

    Article  CAS  Google Scholar 

  40. Satomoto M, Sun Z, Adachi YU et al (2016) Neonatal sevoflurane exposure induces adulthood fear-induced learning disability and decreases glutamatergic neurons in the basolateral amygdala. J Neurosurg Anesthesiol. https://doi.org/10.1097/ANA.0000000000000387

  41. Wilder RT, Flick RP, Sprung J et al (2009) Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology 110:796–804

    Article  Google Scholar 

  42. Kalkman CJ, Peelen L, Moons KG et al (2009) Behavior and development in children and age at the time of first anesthetic exposure. Anesthesiology 110:805–812

    Article  Google Scholar 

  43. DiMaggio C, Sun LS, Kakavouli A et al (2009) A retrospective cohort study of the association of anesthesia and hernia repair surgery with behavioral and developmental disorders in young children. J Neurosurg Anesthesiol 21:286–291

    Article  Google Scholar 

  44. Bartels M, Althoff RR, Boomsma DI (2009) Anesthesia and cognitive performance in children: no evidence for a causal relationship. Twin Res Hum Genet 12:246–253

    Article  Google Scholar 

  45. Hansen TG, Pedersen JK, Henneberg SW et al (2011) Academic performance in adolescence after inguinal hernia repair in infancy: a nationwide cohort study. Anesthesiology 114:1076–1085

    Article  Google Scholar 

  46. Block RI, Thomas JJ, Bayman EO et al (2012) Are anesthesia and surgery during infancy associated with altered academic performance during childhood? Anesthesiology 117:494–503

    Article  Google Scholar 

  47. Davidson AJ, Disma N, de Graaff JC et al (2016) Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet 387:239–250

    Article  Google Scholar 

  48. Sun LS, Li G, Miller TL et al (2016) Association between a single general anesthesia exposure before age 36 months and neurocognitive outcomes in later childhood. JAMA 315:2312–2320

    Article  CAS  Google Scholar 

  49. Hu D, Flick RP, Gleich SJ et al (2016) Construction and characterization of a population-based cohort to study the association of anesthesia exposure with neurodevelopmental outcomes. PLoS One 11:e0155288

    Article  Google Scholar 

  50. Pinyavat T, Warner DO, Flick RP et al (2016) Summary of the update session on clinical neurotoxicity studies. J Neurosurg Anesthesiol 28:356–360

    Article  Google Scholar 

  51. Stratmann G, Lee J, Sall JW et al (2014) Effect of general anesthesia in infancy on long-term recognition memory in humans and rats. Neuropsychopharmacology 39:2275–2287

    Article  CAS  Google Scholar 

  52. Spann MN, Serino D, Bansal R et al (2015) Morphological features of the neonatal brain following exposure to regional anesthesia during labor and delivery. Magn Reson Imaging 33:213–221

    Article  Google Scholar 

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Correspondence to Maiko Satomoto .

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Satomoto, M. (2020). Postoperative Cognitive Function Following General Anesthesia in Children. In: Cascella, M. (eds) General Anesthesia Research. Neuromethods, vol 150. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9891-3_10

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  • DOI: https://doi.org/10.1007/978-1-4939-9891-3_10

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9890-6

  • Online ISBN: 978-1-4939-9891-3

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