Pediatric Neurotoxicity of Anesthetic Agents: Are We too Worried or too Little?

Rashmi Bhatt; Puneet Khanna

doi:10.1055/s-0037-1618323

Journal of Neuroanaesthesiology and Critical Care, Table of Contents

CC-BY-NC-ND 4.0 · J Neuroanaesth Crit Care 2018; 05(01): 3-7
DOI: 10.1055/s-0037-1618323

Review Article

Thieme Medical and Scientific Publishers Private Limited

Pediatric Neurotoxicity of Anesthetic Agents: Are We too Worried or too Little?

Rashmi Bhatt

¹Department of Anaesthesiology, Pain Medicine and Critical Care, AIIMS, New Delhi, India

,

Puneet Khanna

¹Department of Anaesthesiology, Pain Medicine and Critical Care, AIIMS, New Delhi, India

› Author Affiliations

Abstract

The debate on possible neurocognitive adverse effects of anesthetic agents refuses to cease. As evidence builds up, both for and against the debate, a conclusion evades us. More human studies on the subject have now been carried out, and yet we do not have a consensus. In this review, we attempt to relook at the existing evidence, as well as examine some new information as we pursue a greater understanding of this complex matter.

Keywords

anesthetic agents - neonates and infants - neurocognition - neurotoxicity

Full Text

References

References
1 Vutskits L, Davis PJ, Hansen TG. Anesthetics and the developing brain: Time for a change in practice? A pro/con debate.. Paediatr Anaesth 2012; 22: 973-980
2 Rozé JC, Denizot S, Carbajal R, Ancel PY, Kaminski M, Arnaud C. et al. Prolonged sedation and/or analgesia and 5-year neurodevelopment outcome in very preterm infants: Results from the EPIPAGE cohort.. Arch Pediatr Adolesc Med 2008; 162: 728-733
3 Kalkman CJ, Peelen L, Moons KG, Veenhuizen M, Bruens M, Sinnema G. et al. Behavior and development in children and age at the time of first anesthetic exposure.. Anesthesiology 2009; 110: 805-812
4 Bartels M, Althoff RR, Boomsma DI. Anesthesia and cognitive performance in children: No evidence for a causal relationship.. Twin Res Hum Genet 2009; 12: 246-253
5 Guerra GG, Robertson CM, Alton GY, Joffe AR, Cave DA, Dinu IA. et al. Neurodevelopmental outcome following exposure to sedative and analgesic drugs for complex cardiac surgery in infancy.. Paediatr Anaesth 2011; 21: 932-941
6 DiMaggio C, Sun LS, Li G. Early childhood exposure to anesthesia and risk of developmental and behavioral disorders in a sibling birth cohort.. Anesth Analg 2011; 113: 1143-1151
7 Flick RP, Katusic SK, Colligan RC, Wilder RT, Voigt RG, Olson MD. et al. Cognitive and behavioral outcomes after early exposure to anesthesia and surgery.. Pediatrics 2011; 128: e1053-e1061
8 Sun LS, Li G, DiMaggio CJ, Byrne MW, Ing C, Miller TL. et al. Feasibility and pilot study of the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) project.. J Neurosurg Anesthesiol 2012; 24: 382-388
9 Yazar S, Hewitt AW, Forward H, Jacques A, Ing C, von Ungern-Sternberg BS. et al. Early Anesthesia Exposure and the Effect on Visual Acuity, Refractive Error, and Retinal Nerve Fiber Layer Thickness of Young Adults. J Pediatr 2016; 169: 256-259.e1
10 Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vöckler J, Dikranian K. et al. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain.. Science 1999; 283: 70-74
11 Mellon RD, Simone AF, Rappaport BA. Use of anesthetic agents in neonates and young children.. Anesth Analg 2007; 104: 509-520
12 Ikonomidou C, Bittigau P, Ishimaru MJ, Wozniak DF, Koch C, Genz K. et al. Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome.. Science 2000; 287: 1056-1060
13 Bittigau P, Sifringer M, Genz K, Reith E, Pospischil D, Govindarajalu S. et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain.. Proc Natl Acad Sci U S A 2002; 99: 15089-15094
14 Jevtovic-Todorovic V, Hartman RE, Izumi Y, Benshoff ND, Dikranian K, Zorumski CF. et al. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits.. J Neurosci 2003; 23: 876-882
15 Johnson SA, Young C, Olney JW. Isoflurane-induced neuroapoptosis in the developing brain of nonhypoglycemic mice.. J Neurosurg Anesthesiol 2008; 20: 21-28
16 Fredriksson A, Pontén E, Gordh T, Eriksson P. 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 2007; 107: 427-436
17 Rizzi S, Ori C, Jevtovic-Todorovic V. Timing versus duration: Determinants of anesthesia-induced developmental apoptosis in the young mammalian brain.. Ann N Y Acad Sci 2010; 1199: 43-51
18 Yon JH, Daniel-Johnson J, Carter LB, Jevtovic-Todorovic V. Anesthesia induces neuronal cell death in the developing rat brain via the intrinsic and extrinsic apoptotic pathways.. Neuroscience 2005; 135: 815-827
19 Sanders RD, Ma D, Brooks P, Maze M. Balancing paediatric anaesthesia: Preclinical insights into analgesia, hypnosis, neuroprotection, and neurotoxicity.. Br J Anaesth 2008; 101: 597-609
20 Shu Y, Patel SM, Pac-Soo C, Fidalgo AR, Wan Y, Maze M. et al. Xenon pretreatment attenuates anesthetic-induced apoptosis in the developing brain in comparison with nitrous oxide and hypoxia.. Anesthesiology 2010; 113: 360-368
21 Davidson AJ, Becke K, de Graaff J, Giribaldi G, Habre W, Hansen T. et al. Anesthesia and the developing brain: A way forward for clinical research.. Paediatr Anaesth 2015; 25: 447-452
22 Hansen TG, Engelhardt T, Weiss M. The relevance of anesthetic drug-induced neurotoxicity.. JAMA Pediatr 2017; 171: e163481
23 Glatz P, Sandin RH, Pedersen NL, Bonamy AE, Eriksson LI, Granath FN. Academic performance after anesthesia and surgery during childhood: A large-scale nation-wide study.. Anesth Analg 2015; 120: S289
24 Ng E, Taddio A, Ohlsson A. Intravenous midazolam infusion for sedation of infants in the neonatal Intensive Care Unit.. Cochrane Database Syst Rev 2017: 1-CD002052
25 Sanders RD, Xu J, Shu Y, Januszewski A, Haider S, Fidalgo A. et al. Dexmedetomidine attenuates isoflurane-induced neurocognitive impairment in neonatal rats.. Anesthesiology 2009; 110: 1077-1085
26 Yon JH, Carter LB, Reiter RJ, Jevtovic-Todorovic V. Melatonin reduces the severity of anesthesia-induced apoptotic neurodegeneration in the developing rat brain.. Neurobiol Dis 2006; 21: 522-530
27 Straiko MM, Young C, Cattano D, Creeley CE, Wang H, Smith DJ. et al. Lithium protects against anesthesia-induced developmental neuroapoptosis.. Anesthesiology 2009; 110: 862-868
28 Walker K, Holland AJ, Winlaw D, Sherwood M, Badawi N. Neurodevelopmental outcomes and surgery in neonates.. J Paediatr Child Health 2006; 42: 749-751
29 Sanders RD, Hassell J, Davidson AJ, Robertson NJ, Ma D. Impact of anaesthetics and surgery on neurodevelopment: An update.. Br J Anaesth 2013; 110 Suppl 1 i53-172
30 Sanders RD, Manning HJ, Robertson NJ, Ma D, Edwards AD, Hagberg H. et al. Preconditioning and postinsult therapies for perinatal hypoxic-ischemic injury at term.. Anesthesiology 2010; 113: 233-249
31 Zhang X, Liu F, Slikker Jr. W, Wang C, Paule MG. Minimally invasive biomarkers of general anesthetic-induced developmental neurotoxicity.. Neurotoxicol Teratol 2017; 60: 95-101
32 Morton NS. Local and regional anaesthesia in infants. Continuing education in anaesthesia.. Critical Care and Pain 2004; 4 (05) 169-171