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Neurotoxicity of ketamine and nitrous oxide

  • Conference paper
Anaesthesia, Pain, Intensive Care and Emergency Medicine — A.P.I.C.E.

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Abstract

Since its first clinical administration in 1965 by Corssen and Domino [1], the dissociative anaesthetic ketamine, a derivative of phencyclidine (PCP), has been used in many clinical settings. Unlike other intravenous anaesthetics (e.g. barbiturates, benzodiazepines, propofol), ketamine provides significant analgesia without depressing cardiovascular and respiratory functions. Therefore it is frequently used for sedation of paediatric and critically ill patients.

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References

  1. Corssen G, Domino EF (1966) Dissociative anesthesia: further pharmacologic studies and first clinical experiences with the phencyclidine derivative CI-581. Anesth Analg 45: 29

    Article  PubMed  CAS  Google Scholar 

  2. Gonsowski CT, Eger II EI (1994) Nitrous oxide minimum alveolar anesthetic concentration in rats is greater than previously reported. Anesth Analg 79: 710–712

    Article  PubMed  CAS  Google Scholar 

  3. Hornbein TF, Eger EI II, Winter PM et al (1982) The minimum alveolar concentration of nitrous oxide in man. Anesth Analg 61: 553–556

    Article  PubMed  CAS  Google Scholar 

  4. Franks NP, Lieb WR (1994) Molecular and cellular mechanism of general anesthesia. Nature 367: 607–614

    Article  PubMed  CAS  Google Scholar 

  5. Nishikawa K, MacIver MB (2001) Agent-selective effects of volatile anesthetics on GABAA receptor-mediated synaptic inhibition in hippocampal interneurons. Anesthesiology 94: 340–347

    Article  PubMed  CAS  Google Scholar 

  6. Lodge D, Anis NA (1982) Effects of phencyclidine on excitatory amino acid activation of spinal interneurons in the cat. Eur J Pharmacol 77: 203–204

    Article  PubMed  CAS  Google Scholar 

  7. Jevtovic-Todorovic V, Todorovic SM, Mennerick S et al (1998) Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nat Med 4: 460–463

    Article  PubMed  CAS  Google Scholar 

  8. Mennerick S, Jevtovic-Todorovic V, Todorovic SM et al (1998) Effect of nitrous oxide on excitatory and inhibitory synaptic transmission in hippocampal cultures. J Neurosci 18: 9716–9726

    PubMed  CAS  Google Scholar 

  9. Stevens WC, Kingston HGG (1992) Inhalation anesthesia. In: Barash PG et al (eds) Clinical anesthesia. Lippincott, Philadelphia, pp 439–465

    Google Scholar 

  10. Fragren RJ and Avram MJ (1992) Nonopioid intravenous anesthetesia. In: Barash PG et al (eds) Clinical anesthesia. Lippincott, Philadelphia, pp 385–412

    Google Scholar 

  11. Luby ED, Gottlieb JS, Cohen BD et al (1962) Model psychosis and schizophrenia. Am J Psychiatry 119: 61

    Google Scholar 

  12. Krystal JH, Karper LP, Seibyl JP et al (1993) Dose-related effects of the NMDA antagonist, ketamine, in healthy humans. Schizophr Res 9: 240–241

    Article  Google Scholar 

  13. Newcomer JW, Farber NB, Jevtovic-Todorovic V et al (1999) Ketamine-induced NMDA receptor hypofunction as a model of memory impairment in schizophrenia. Neuropsychopharmacology 20: 106–118

    Article  PubMed  CAS  Google Scholar 

  14. Magbagbeola JAO, Thomas NA (1974) Effect of thiopentone on emergence reactions to ketamine anaesthesia. Can Anaesth Soc J 21: 321

    Article  PubMed  CAS  Google Scholar 

  15. White PF, Way WL, Trevor AJ (1982) Ketamine — its pharmacology and therapeutic uses. Anesthesiology 56: 1 19

    Google Scholar 

  16. Bovill JG, Coppell, L. Dundee JW et al (1971) Current status of ketamine anesthesia. Lancet 1: 1285

    Article  PubMed  CAS  Google Scholar 

  17. Dohrn CS, Lichtor JL, Coalson DW et al (1993) Related articles, links reinforcing effects of extended inhalation of nitrous oxide in humans. Drug Alcohol Depend 31: 265–280

    Article  PubMed  CAS  Google Scholar 

  18. Gillman MA (1992) Nitrous oxide abuse in perspective. Clinical Neuropharmacol 15: 297–306

    Article  CAS  Google Scholar 

  19. Herrling PL (1994) D-CPPene (SDZ EAA 494), a competitive NMDA antagonist: results from animal models and first results in humans. Neuropsychopharmacology 10: (Part 1):591 S

    Google Scholar 

  20. Grotta J (1995) Why do all drugs work in animals but none in stroke patients? 2. Neuroprotective therapy. J Intern Med 237: 89

    Article  PubMed  CAS  Google Scholar 

  21. Olney JW, Labruyere J, Price MT (1989) Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science 244: 1360

    Article  PubMed  CAS  Google Scholar 

  22. Jevtovic-Todorovic V, Wozniak DW, Benshoff ND et al (2001) Comparative evaluation of the neurotoxic properties of ketamine and nitrous oxide. Brain Res 895: 264–267

    Article  PubMed  CAS  Google Scholar 

  23. Jevtovic-Todorovic V, Benshoff N, Olney JW (1998) Prolonged nitrous oxide anesthesia kills neurons in the adult rat brain. J Neurosurg Anesthesiol 10: 257

    Google Scholar 

  24. Livingston A, Waterman AE (1977) Influence of age and sex on the duration of action of ketamine in rats. Br J Pharmacol 59: 491

    Google Scholar 

  25. Hong K, Trudell JR, O’Neil JR et al (1980) Metabolism of nitrous oxide by human and rat intestinal contents. Anesthesiology 52: 16–19

    Article  PubMed  CAS  Google Scholar 

  26. Jevtovic-Todorovic V, Benshoff N, Olney JW (2000) Ketamine potentiates cerebrocortical damage induced by the common anesthetic agent nitrous oxide in adult rats. Br J Pharmacol 130: 1692–1698

    Article  PubMed  CAS  Google Scholar 

  27. Wozniak DF, Dikranian K, Ishimaru MJ et al (1998) Disseminated corticolimbic neuronal degeneration induced in rat brain by MK-801: potential relevance to Alzheimer’s disease. Neurobiol Dis 5: 305–322

    Article  PubMed  CAS  Google Scholar 

  28. Corso TD, Sesma MA, Tenkova TI et al (1997) Multifocal brain damage induced by phencyclidine is augmented by pilocarpine. Brain Res 752: 1–14

    Article  PubMed  CAS  Google Scholar 

  29. Olney JW, Labruyere J, Wang G et al (1991) NMDA antagonist neurotoxicity: mechanism and protection. Science 254: 1515–1518

    Article  PubMed  CAS  Google Scholar 

  30. Olney JW, Farber NB (1995) NMDA antagonists as neurotherapeutic drugs, psychotogens, neurotoxins, and research tools for studying schizophrenia. Neuropsychopharmacology 13: 335–345

    Article  PubMed  CAS  Google Scholar 

  31. Jevtovic-Todorovic V, Kirby CO, Olney JW (1997) Isoflurane and propofol block neurotoxicity caused by MK-801 in the rat posterior cingulate/retrosplenial cortex. Cereb Blood Flow Metab 17: 168–174

    CAS  Google Scholar 

  32. Ishimaru M, Fukamauchi F, Olney JW (1995) Halothane prevents MK-801 neurotoxicity in the rat cingulate cortex. Neurosci Lett 193: 1–4

    Article  PubMed  CAS  Google Scholar 

  33. Farber NB, Foster J, Duhan NL et al (1995) Alpha 2 adrenergic agonists prevent MK-801 neurotoxicity. Neuropsychopharmacology 12: 347–349

    Article  PubMed  CAS  Google Scholar 

  34. Farber NB, Foster J, Duhan NL et al (1996) Olanzapine and fluperlapine mimic clozapine in preventing MK-801 neurotoxicity. Schizophr Res 21: 33–37

    Article  PubMed  CAS  Google Scholar 

  35. Farber NB, Hanslick J, Kirby C et al (1998) Serotonergic agents that activate 5HT2A receptors prevent NMDA antagonist neurotoxicity. Neuropsychopharmacology 18: 57–62

    Article  PubMed  CAS  Google Scholar 

  36. Farber NB, Kim SH, Dikranian K et al (2002) Receptor mechanisms and circuitry underlying NMDA antagonist neurotoxicity. Mol Psychiatry 7: 32–43

    Article  PubMed  CAS  Google Scholar 

  37. Gonzales RA, Brown LM, Jones TW et al (1991) N-Methyl-D-aspartate mediated responses decrease with age in Fischer 344 rat brain. Neurobiol Aging 12: 219–225

    Article  PubMed  CAS  Google Scholar 

  38. Magnusson KR, Cotman CW (1993) Age-related changes in excitatory amino acid receptors in two mouse strains. Neurobiol Aging 14: 197–206

    Article  PubMed  CAS  Google Scholar 

  39. Wenk GL, Walker LC, Price DL et al (1991) Loss of NMDA, but not GABA-A, binding in the brains of aged rats and monkeys. Neurobiol Aging 12: 93–98

    Article  PubMed  CAS  Google Scholar 

  40. Beals JK, Carter LB, Jevtovic-Todorovic V (2003) Neurotoxicity of nitrous oxide and ketamine is more severe in aged than in young rat brain. Ann NY Acad Sci 993: 1

    Article  Google Scholar 

  41. Farber NB, Wozniak DF, Price MT et al (1995) Age-specific neurotoxicity in the rat associated with NMDA receptor blockade: potential relevance to schizophrenia? Biol Psychiatry 38: 788–796

    Article  PubMed  CAS  Google Scholar 

  42. 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  PubMed  CAS  Google Scholar 

  43. Young C, Tenkova T, Wang H et al (2003) A single sedating dose of ketamine causes neuronal apoptosis in developing mouse brain (abstract). Soc Neurosci (in press)

    Google Scholar 

  44. 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

    PubMed  CAS  Google Scholar 

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Authors
  1. V. Jevtovic-Todorovic
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Editors and Affiliations

  1. Department of Perioperative Medicine, Intensive Care and Emergency, Trieste University School of Medicine, Trieste, Italy

    Antonino Gullo M.D. (Head) (Head)

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© 2004 Springer-Verlag Italia, Milano

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Jevtovic-Todorovic, V. (2004). Neurotoxicity of ketamine and nitrous oxide. In: Gullo, A. (eds) Anaesthesia, Pain, Intensive Care and Emergency Medicine — A.P.I.C.E.. Springer, Milano. https://doi.org/10.1007/978-88-470-2189-1_21

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  • DOI: https://doi.org/10.1007/978-88-470-2189-1_21

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-0235-7

  • Online ISBN: 978-88-470-2189-1

  • eBook Packages: Springer Book Archive

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