Are anaesthetics toxic to the brain?

British Journal of Anaesthesia

Volumn 107, Issue 1, 2011, Pages 30-37

  Hudson, A E ^a   Hemmings, H C ^a  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

Alzheimers disease; anaesthesia, general; neurobehavioural manifestations; postoperative complications

Indexed keywords

4 AMINOBUTYRIC ACID; CLONAZEPAM; DESFLURANE; DIAZEPAM; ETOMIDATE; ISOFLURANE; KETAMINE; MIDAZOLAM; NITROUS OXIDE; PENTOBARBITAL; PROPOFOL; SEVOFLURANE; XENON;

AGING; ALZHEIMER DISEASE; ANESTHESIA COMPLICATION; APOPTOSIS; BRAIN DEVELOPMENT; COGNITIVE DEFECT; DRUG INDUCED DISEASE; DRUG MECHANISM; DRUG TARGETING; GENERAL ANESTHESIA; GERIATRIC ANESTHESIA; HUMAN; NERVE DEGENERATION; NEUROPATHOLOGY; NEUROPROTECTION; NEUROTOXICITY; NEUROTRANSMISSION; NONHUMAN; PEDIATRIC ANESTHESIA; POSTOPERATIVE COMPLICATION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SYNAPTOGENESIS;

EID: 79959463061     PISSN: 00070912     EISSN: 14716771     Source Type: Journal    
DOI: 10.1093/bja/aer122     Document Type: Review

References (69)

1. Rudolph U, Antkowiak B. Molecular and neuronal substrates for general anaesthetics. Nat Rev Neurosci 2004; 5: 709-20 (Pubitemid 39150142)
2. Hemmings HC Jr., Akabas MH, Goldstein PA, Trudell JR, Orser BA, Harrison NL. Emerging molecular mechanisms of general anesthetic action. Trends Pharmacol Sci 2005; 26: 503-10 (Pubitemid 41338560)
3. Jurd R, Arras M, Lambert S, et al. General anesthetic actions in vivo strongly attenuated by a point mutation in the GABA(A) receptor beta3 subunit. FASEB J 2003; 17: 250-2
4. Fütterer CD, Maurer MH, Schmitt A, Feldmann RE Jr, Kuschinsky W, Waschke KF. Alterations in rat brain proteins after desflurane anesthesia. Anesthesiology 2004; 100: 302-8 (Pubitemid 38133697)
5. Culley DJ, Yukhananov RY, Xie Z, Gali RR, Tanzi RE, Crosby G. Altered hippocampal gene expression 2 days after general anesthesia in rats. Eur J Pharmacol 2006; 549: 71-8 (Pubitemid 44441270)
6. Oppenheim RW. Cell death during development of the nervous system. Annu Rev Neurosci 1991; 14: 453-501
7. Rakic S, Zecevic N. Programmed cell death in the developing human telencephalon. Eur J Neurosci 2000; 12: 2721-34
8. 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. Neuro-science 2005; 135: 815-27
9. Veyckemans F. Excitation phenomena during sevoflurane anaesthesia in children. Curr Opin Anaesthesiol 2001; 14: 339-43 (Pubitemid 32530472)
10. Constant I, Seeman R, Murat I. Sevoflurane and epileptiform EEG changes. Paediatr Anaesth 2005; 15: 266-74 (Pubitemid 40462800)
11. Harrison JL. Postoperative seizures after isoflurane anesthesia. Anesth Anal 1986; 65: 1235-6 (Pubitemid 16005561)
12. Zeiler SR, Kaplan PW. Propofol withdrawal seizures (or not). Seizure 2008; 17: 665-7
13. Dzhala VI, Talos DM, Sdrulla DA, et al. NKCC1 transporter facilitates seizures in the developing brain. Nat Med 2005; 11: 1205-13 (Pubitemid 43093668)
14. Ikonomidou C, Bosch F, Miksa M, et al. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 1999; 283: 70-4 (Pubitemid 29044848)
15. Scallet AC, Schmued LC, Slikker W Jr, et al. Developmental neuro-toxicity of ketamine: morphometric confirmation, exposure parameters, and multiple fluorescent labeling of apoptotic neurons. Toxicol Sci 2004; 81: 364-70 (Pubitemid 39377966)
16. Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure to common anesthetic agents causes widespread neurodegenera-tion in the developing rat brain and persistent learning deficits. J Neurosci 2003; 23: 876-82 (Pubitemid 36206178)
17. Istaphanous GK, Howard J, Nan X, et al. Comparison of the neu-roapoptotic properties of equipotent anesthetic concentrations of desflurane, isoflurane, or sevoflurane in neonatal mice. Anesthesiology 2011; 114: 578-87
18. Young C, Jevtovic-Todorovic V, Qin YQ, et al. Potential of ketamine and midazolam, individually or in combination, to induce apopto-tic neurodegeneration in the infant mouse brain. Br J Pharmacol 2005; 146: 189-97 (Pubitemid 43079958)
19. Ikonomidou C, Bittigau P, Ishimaru MJ, et al. Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science 2000; 287: 1056-60 (Pubitemid 30094364)
20. Bittigau P, Sifringer M, Genz K, et al. Antiepileptic drugs and apop-totic neurodegeneration in the developing brain. Proc Natl Acad Sci USA 2002; 99: 15089-94 (Pubitemid 35334614)
21. Cattano D, Young C, Straiko MM, Olney JW. Subanesthetic doses of propofol induce neuroapoptosis in the infant mouse brain. Anesth Analg 2008; 106: 1712-4
22. Kahraman S, Zup SL, McCarthy MM, Fiskum G. GABAergic mechanism of propofol toxicity in immature neurons. J Neurosurg Anesthesiol 2008; 20: 233-40
23. Ma D, Williamson P, Januszewski A, et al. Xenon mitigates isoflurane-induced neuronal apoptosis in the developing rodent brain. Anesthesiology 2007; 106: 746-53 (Pubitemid 46555618)
24. Cattano D, Williamson P, Fukui K, et al. Potential of xenon to induce or to protect against neuroapoptosis in the developing mouse brain. Can J Anaesth 2008; 55: 429-36 (Pubitemid 351976619)
25. Olney JW, Young C, Wozniak DF, Ikonomidou C, Jevtovic-Todorovic V. Anesthesia-induced developmental neuroa-poptosis. Does it happen in humans? Anesthesiology 2004; 101: 273-5 (Pubitemid 38988479)
26. Edwards DA, Shah HP, Cao W, Gravenstein N, Seubert CN, Martynyuk AE. Bumetanide alleviates epileptogenic and neuro-toxic effects of sevoflurane in neonatal rat brain. Anesthesiology 2010; 112: 567-75
27. Stratmann G, Sall JW, May LD, et al. Isoflurane differentially affects neurogenesis and long-term neurocognitive function in 60-day-old and 7-day-old rats. Anesthesiology 2009; 110: 834-48
28. Zhu C, Gao J, Karlsson N, et al. Isoflurane anesthesia induced persistent, progressive memory impairment, caused a loss of neural stem cells, and reduced neurogenesis in young, but not adult, rodents. J Cereb Blood Flow Metab 2010; 30: 1017-30
29. Slikker W Jr., Zou X, Hotchkiss CE, et al. Ketamine-induced neur-onal cell death in the perinatal rhesus monkey. Toxicol Sci 2007; 98: 145-58 (Pubitemid 47073827)
30. Paule MG, Li M, Allen RR, et al. Ketamine anesthesia during the first week of life can cause long-lasting cognitive deficits in rhesus monkeys. Neurotoxicol Teratol 2011; 33: 220-30
31. Paule MG, Cranmer JM, Wilkins JD, Stern HP, Hoffman EL. Quanti-tation of complex brain function in children: preliminary evaluation using a nonhuman primate behavioral test battery. Neurotoxicology 1988; 9: 367-78
32. Brambrink AM, Evers AS, Avidan MS, et al. Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology 2010; 112: 834-41
33. Zou X, Patterson TA, Divine RL, et al. Prolonged exposure to keta-mine increases neurodegeneration in the developing monkey brain. Int J Dev Neurosci 2009; 27: 727-31
34. Clancy B, Finlay BL, Darlington RB, Anand KJ. Extrapolating brain development from experimental species to humans. Neurotoxi-cology 2007; 28: 931-7 (Pubitemid 47519794)
35. 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
36. DiMaggio C, Sun LS, Kakavouli A, Byrne MW, Li G. A retrospective cohort study of the association of anesthesia and hernia repair surgery with behavioral and developmental disorders in young children. J Neurosurg Anesthesiol 2009; 21: 286-91
37. Bartels M, Althoff RR, Boomsma DI. Anesthesia and cognitive performance in children: no evidence for a causal relationship. Twin Res Hum Genet 2009; 12: 246-53
38. Davidson AJ, McCann ME, Morton NS, Myles PS. Anesthesia and outcome after neonatal surgery: the role for randomized trials. Anesthesiology 2008; 109: 941-4
39. Sun LS, Li G, Dimaggio C, et al. Coinvestigators of the Pediatric Anesthesia Neurodevelopment Assessment (PANDA) Research Network. Anesthesia and neurodevelopment in children: time for an answer? Anesthesiology 2008; 109: 757-61
40. Moller JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet 1998; 351: 857-61 (Pubitemid 28121173)
41. Deiner S, Silverstein JH. Postoperative delirium and cognitive dysfunction. Br J Anaesth 2009; 103 (Suppl. 1): i41-46
42. Wei H, Xie Z. Anesthesia, calcium homeostasis and Alzheimer's disease. Curr Alzheimer Res 2009; 6: 30-5
43. Wan Y, Xu J, Ma D, Zeng Y, Cibelli M, Maze M. Postoperative impairment of cognitive function in rats: a possible role for cytokine-mediated inflammation in the hippocampus. Anesthesiology 2007; 106: 436-43 (Pubitemid 46662208)
44. Sall JW, Stratmann G, Leong J, et al. Isoflurane inhibits growth but does not cause cell death in hippocampal neural precursor cells grown in culture. Anesthesiology 2009; 110: 826-33
45. Bohnen NI, Warner MA, Kokmen E, Beard CM, Kurland LT. Alzheimer's disease and cumulative exposure to anesthesia: a case-control study. J Am Geriatr Soc 1994; 42: 198-201 (Pubitemid 24057360)
46. Xie Z, Culley DJ, Dong Y, et al. The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid beta-protein level in vivo. Ann Neurol 2008; 64: 618-27
47. Alonso A, Zaidi T, Novak M, Grundke-Iqbal I, Iqbal K. Hyperpho-sphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proc Natl Acad Sci USA 2001; 98: 6923-8 (Pubitemid 32538318)
48. Tanzi RE, Bertram L. Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective. Cell 2005; 120: 545-55. (Pubitemid 40269768)
49. Douglas PM, Dillin A. Protein homeostasis and aging in neurode-generation. J Cell Biol 2010; 190: 719-29
50. Wei H, Liang G, Yang H, et al. The common inhalational anesthetic isoflurane induces apoptosis via activation of inositol 1,4,5-trisphosphate receptors. Anesthesiology 2008; 108: 251-60 (Pubitemid 351156735)
51. Zhen Y, Dong Y, Wu X, et al. Nitrous oxide plus isoflurane induces apoptosis and increases beta-amyloid protein levels. Anesthesiology 2009; 111: 741-52
52. Dong Y, Zhang G, Zhang B, et al. The common inhalational anesthetic sevoflurane induces apoptosis and increases beta-amyloid protein levels. Arch Neurol 2009; 66: 620-31
53. Zhang B, Dong Y, Zhang G, et al. The inhalation anesthetic des-flurane induces caspase activation and increases amyloid beta-protein levels under hypoxic conditions. J Biol Chem 2008; 283: 11866-75
54. Eckenhoff RG, Johansson JS, Wei H, et al. Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. Anesthesiology 2004; 101: 703-9 (Pubitemid 39121650)
55. Mandal PK, Pettegrew JW. Abeta peptide interactions with isoflur-ane, propofol, thiopental and combined thiopental with halothane: a NMR study. Biochim Biophys Acta 2008; 1778: 2633-9
56. Bianchi SL, Tran T, Liu C, et al. Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics. Neurobiol Aging 2008; 29: 1002-10 (Pubitemid 351711665)
57. Li L, Peng L, Zuo Z. Isoflurane preconditioning increases B-cell lymphoma-2 expression and reduces cytochrome c release from the mitochondria in the ischemic penumbra of rat brain. Eur J Pharmacol 2008; 586: 106-13
58. Codaccioni JL, Velly LJ, Moubarik C, Bruder NJ, Pisano PS, Guillet BA. Sevoflurane preconditioning against focal cerebral ischemia: inhibition of apoptosis in the face of transient improvement of neurological outcome. Anesthesiology 2009; 110: 1271-8
59. Wei H, Liang G, Yang H. Isoflurane preconditioning inhibited isoflurane-induced neurotoxicity. Neurosci Lett 2007; 425: 59-62 (Pubitemid 47411660)
60. Planel E, Richter KE, Nolan CE, et al. Anesthesia leads to tau hyperphosphorylation through inhibition of phosphatase activity by hypothermia. J Neurosci 2007; 27: 3090-7 (Pubitemid 46474135)
61. Whittington RA, Virág L, Marcouiller F, et al.. Propofol directly increases tau phosphorylation. PLoS One 2011; 6: e16648
62. Cibelli M, Fidalgo AR, Terrando N, et al. Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol 2010; 68: 360-8
63. Terrando N, Monaco C, Ma D, Foxwell BM, Feldmann M, Maze M. Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci USA 2010; 107: 20518-22
64. Rosczyk HA, Sparkman NL, Johnson RW. Neuroinflammation and cognitive function in aged mice following minor surgery. Exp Gerontol 2008; 43: 840-6
65. Wu X, Lu Y, Dong Y, et al. The inhalation anesthetic isoflurane increases levels of proinflammatory TNF-a, IL-6, and IL-1b. Neu-robiol Aging 2010
66. Gasparini M, Vanacore N, Schiaffini C, et al. A case-control study on Alzheimer's disease and exposure to anesthesia. Neurol Sci 2002; 23: 11-4 (Pubitemid 34591412)
67. Bohnen N, Warner MA, Kokmen E, Kurland LT. Early and midlife exposure to anesthesia and age of onset of Alzheimer's disease. Int J Neurosci 1994b; 77: 181-5 (Pubitemid 2144593)
68. Avidan MS, Searleman AC, Storandt M, et al. Long-term cognitive decline in older subjects was not attributable to noncardiac surgery or major illness. Anesthesiology 2009; 111: 964-70
69. Sanders RD, Ma D, Brooks P, Maze M. Balancing paediatric anaesthesia: preclinical insights into analgesia, hypnosis, neuroprotec-tion, and neurotoxicity. Br J Anaesth 2008; 101: 597-609