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Postoperative encephalopathy: Pathophysiological and morphological bases of its prevention under general anesthesia

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In vitro and in vivo studies have provided sufficient evidence of the neurotoxicity of general anesthetics and their ability to cause postoperative cognitive dysfunction (POCD). The latter is one of the undesirable phenomena associated with general anesthesia. Recently, the prevention of postoperative cognitive impairments has been of particular relevance because of their high incidence, longer length of hospital stay, higher cost of treatment, worse quality of life in patients, and no approaches to drug correction and prevention. The review gives data on the negative effects of general anesthesia in patients of different age groups, highlights the pathogenetic mechanisms of POCD, and proposes its possible drug prevention and treatment strategies: identification of patients at high risk for POCD and both pre- and postoperative neuropsychological testing; intraoperative POCD prevention using a package of measures and, if inefficient, drug correction of found cognitive impairments just in the early postoperative period.

About the Authors

A. M. Ovezov
M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia 61/2, Shchepkin St., Moscow 129110
Russian Federation

A. V. Knyazev
M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia 61/2, Shchepkin St., Moscow 129110
Russian Federation

M. V. Panteleeva
M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia 61/2, Shchepkin St., Moscow 129110
Russian Federation

M. A. Lobov
M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia 61/2, Shchepkin St., Moscow 129110
Russian Federation

M. N. Borisova
M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia 61/2, Shchepkin St., Moscow 129110
Russian Federation

A. V. Lugovoy
M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia 61/2, Shchepkin St., Moscow 129110
Russian Federation


1. Эйткенхед AР, Смит Г. Руководство по анестезиологии. Том 2. Москва: Медицина; 1999. 552 c. [Eitkenkhed AR, Smit G. Rukovodstvo po anesteziologii [Guide in anesthesiology]. Vol. 2. Moscow: Meditsina; 1999. 552 p.].

2. Chong KY, Gelb AW. Cerebrovascular and cerebral metabolic effects of commonly used anaesthetics. Ann Acad Med Singapore. 1994 Nov;23(6 Suppl):145–9.

3. Hudson AE, Hemmings HC Jr. Are anaesthetics toxic to the brain? Br J Anaesth. 2011 Jul;107(1):30–7. doi: 10.1093/bja/aer122. Epub 2011 May 26.

4. Levin ED, Uemura E, Bowman RE. Neurobehavioral toxicology of halothane in rats. Neurotoxicol Teratol. 1991 Jul-Aug;13(4):461–70

5. Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing ratbrain and persistent learning deficits. J Neurosci. 2003 Feb 1;23(3):876–82.

6. Brambrink AM, Evers AS, Avidan MS, et al. Isoflurane-induced Neuroapoptosis in the Neonatal Rhesus Macaque Brain. Anesthesiology. 2010 Apr;112(4):834–41. doi: 10.1097/ALN.0b013e3181d049cd.

7. Fredriksson A, Ponten 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 Sep;107(3):427–36.

8. Johnson SA, Young C, Olney JW. Isofluraneinduced neuroapoptosis in the developing brain of non-hypoglycemic mice. J Neurosurg Anesthesiol. 2008 Jan;20(1):21–8.

9. Paule MG, Li M, Allen RR, et al. Ketamine anesthesia during the first week of life can ause long-lasting cognitive deficits in rhesus monkeys. Neurotoxicol Teratol. 2011 Mar- Apr;33(2):220–30. doi: 10.1016/ 01.001. Epub 2011 Jan 15.

10. Slikker W Jr, Zou X, Hotchkiss CE, et al. Ketamine induced neuronal cell death in the perinatal rhesus monkey. Toxicol Sci. 2007 Jul;98(1):145–58. Epub 2007 Apr 10.

11. Zou X, Patterson TA, Divine RL, et al. Prolonged exposure to ketamine increases neurodegeneration in the developing monkey brain. Int J Dev Neurosci. 2009 Nov;27(7):727–31. doi: 10.1016/j.ijdevneu.2009.06.010. Epub 2009 Jul 4.

12. Block RI, Thomas JJ, Bayman EO, et al. Are anesthesia and surgery during infancy associated with altered academic performance during childhood? Anesthesiology. 2012 Sep;117(3):494–503.

13. Лобов МА, Болевич СБ, Дубовая ТК и др. Патофизиологические и морфологические основы периоперационной церебропротекции. Новости анестезиологии и реаниматологии. 2011;(3):10–3. [Lobov MA, Bolevich SB, Dubovaya TK, et al. Pathophysiological and morphological basis of perioperative cerebral protection. Novosti anesteziologii i reanimatologii.2011;(3):10–3. (In Russ.)].

14. Soriano SG, Anand KJ, Rovnaghi CR, Hickey PR. Of mice and men: should we extrapolate rodent experimental data to the care of human neonates? Anesthesiology. 2005 Apr;102(4):866–8; author reply 868-9.

15. Scallet AC, Schmued LC, Slikker W Jr, et al. Developmental neurotoxicity of ketamine: morphometric confirmation, exposure parameters, and multiple fluorescent labeling of apoptotic neurons. Toxicol Sci. 2004 Oct;81(2):364–70. Epub 2004 Jul 14.

16. Bartels M, Althoff RR, Boomsma DI. Anesthesia and cognitive performance in children: no evidence for a causal relationship. Twin Res Hum Genet. 2009 Jun;12(3):246–53. doi: 10.1375/twin.12.3.246.

17. 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 Nov;113(5):1143–51. doi: 10.1213/ANE. 0b013e3182147f42. Epub 2011 Mar 17.

18. Hansen TG, Pedersen JK, Henneberg SW, et al. Academic performance in adolescence after inguinal hernia repair in infancy: a nationwide cohort study. Anesthesiology. 2011 May;114(5):1076–85. doi: 10.1097/ALN.0b013e31820e77a0.

19. Kalkman CJ, Peelen L, Moons KG, et al. Behavior and development in children and age at the time of first anesthetic exposure. Anesthesiology. 2009 Apr;110(4):805–12. doi: 10.1097/ALN.0b013e31819c7124.

20. Sprung J, Flick RP, Wilder RT, et al. Anesthesia for cesarean delivery and learning disabilities in a population-based birth cohort. Anesthesiology. 2009 Aug;111(2):302–10. doi: 10.1097/ALN.0b013e3181adf481.

21. Wilder RT, Flick RP, Sprung J, et al. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology. 2009 Apr;110(4):796–804. doi: 10.1097/01.anes.0000344728.34332.5d.

22. Moller JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive ysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet. 1998 Mar 21;351(9106):857–61.

23. Rasmussen LS, Larsen K, Houx P, et al. ISPOCD group. The assessment of postoperative cognitive function. Acta Anaesthesiol Scand. 2001 Mar;45(3):275-89.

24. Demeure MJ, Fain MJ. The elderly surgical patient and postoperative delirium. J Am Coll Surg. 2006 Nov;203(5):752–7. Epub 2006 Sep 26.

25. Большедворов РВ, Кичин ВВ, Федоров СА, Лихванцев ВВ. Эпидемиология послеоперационных когнитивных расстройств. Анестезиология и реаниматология. 2009;(3):20–4. [Bol'shedvorov RV, Kichin VV, Fedorov SA, Likhvantsev VV. Epidemiology of postoperative cognitive disorders. Anesteziologiya i reanimatologiya. 2009;(3):20–4. (In Russ.)].

26. Evered L, Scott DA, Silbert B, Maruff P. Postoperative cognitive dysfunction is ndependent of type of surgery and anesthetic. Anesth Analg. 2011 May;112(5):1179–85. doi: 10.1213/ANE.0b013e318215217e. Epub 2011 Apr 7.

27. Monk TG, Weldon BC, Garvan CW, et al. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology. 2008 Jan;108(1):18–30.

28. Burkhart CS, Steiner LA. Can Postoperative Cognitive Dysfunction Be Avoided? Hosp ract (1995). 2012 Feb;40(1):214–23. doi: 10.3810/hp.2012.02.962.

29. Федоров СА, Большедворов РВ, Лихванцев ВВ. Причины ранних расстройств психики больного после операций, выполненных в условиях общей анестезии. Вестник интенсивной терапии. 2007;(4):17–25. [Fedorov SA, Bol'shedvorov RV, Likhvantsev VV. Causes of early disorders of the psyche of the patient after operations performed under general anesthesia. Vestnik intensivnoi terapii. 2007;(4):17–25. (In Russ.)].

30. Vacas S, Degos V, Feng X, Maze M. The neuroinflammatory response of postoperative cognitive decline. Br Med Bull. 2013;106:161–78. doi: 10.1093/bmb/ldt006. Epub 2013 Apr 4.

31. Yin C, Gou LS, Liu Y, et al. Repeated administration of propofol upregulated the expression of c-Fos and cleaved-caspase-3 proteins in the developing mouse brain. Indian J Pharmacol. 2011 Nov;43(6):648–51. doi: 10.4103/0253-7613.89819.

32. Pratico C, Quattrone D, Lucanto T, et al.Drugs of anesthesia acting on central cholinergic system may cause post-operative cognitive dysfunction and delirium. Med Hypotheses. 2005;65(5):972–82.

33. Cibelli M, Fidalgo AR, Terrando N, et al. Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol. 2010 Sep;68(3):360–8. doi: 10.1002/ana.22082.

34. Loop T, Dovi-Akue D, Frick M, et al. Volatile anesthetics induce caspase-dependent, mitochondria-mediated apoptosis in human T lymphocytes in vitro. Anesthesiology. 2005 Jun;102(6):1147–57.

35. Князев АВ, Пантелеева МВ. Неврологические осложнения у детей с врожденными пороками сердца в предоперационном, интраоперационном и постоперационном периодах. Альманах клинической медицины. 2001;(4):254–9. [Knyazev AV, Panteleeva MV. Neurologic complications in children with congenital heart disease in the preoperative, intraoperative and postoperative periods. Al'manakh klinicheskoi meditsiny. 2001;(4):254– .

36. (In Russ.)].

37. Лобов МА, Болевич СБ, Гринько АН и др. Церебральные и метаболические нарушения при оперативных вмешательствах под общим обезболиванием у детей. Альманах клинической медицины. 2006;(8):170–2. [Lobov MA, Bolevich SB, Grin'ko AN, et l. Cerebral and metabolic disorders during surgery under general anesthesia in children. Al'manakh klinicheskoi meditsiny. 2006;(8):170–2].

38. Arora SS, Gooch JL, Garcia PS. Postoperative cognitive dysfunction, Alzheimer's disease, and anesthesia. Int J Neurosci. 2014;124(4):236–42.

39. Perucho J, Rubio I, Casarejos MJ, et al. Anesthesia with isoflurane increases amyloid pathology in mice models of Alzheimer’s disease. J Alzheimers Dis. 2010;19(4):1245–57. doi: 10.3233/JAD-2010-1318.

40. Run X, Liang Z, Zhang L, et al. Anesthesia induces phosphorylation of tau. J Alzheimers Dis. 2009;16(3):619–26. doi: 10.3233/JAD- 2009-1003.

41. Zhang B, Dong Y, Zhang G, et al. The inhalation anesthetic desflurane induces caspase activation and increases amyloid betaprotein levels under hypoxic conditions. J Biol Chem. 2008 May 2;283(18):11866–75. doi: 10.1074/jbc.M800199200. Epub 2008 Mar 6.

42. Avidan MS, Evers AS. Review of clinical evidence for persistent cognitive decline or incident dementia attributable to surgery or general anesthesia. J Alzheimers Dis. 2011;24(2):201–16. doi: 10.3233/JAD-2011-101680.

43. Chen PL, Yang CW, Tseng YK, et al. Risk of dementia after anaesthesia and surgery. Br J Psychiatry. 2014 Mar;204(3):188–93. doi: 10.1192/bjp.bp.112.119610. Epub 2013 Jul 25.

44. Gasparini M, Vanacore N, Schiaffini C, et al. A case-control study on Alzheimer’s disease and exposure to anesthesia. Neurol Sci. 2002 Apr;23(1):11–4.

45. Steinmetz J, Siersma V, Kessing LV, Rasmussen LS; ISPOCD Group. Is postoperative cognitive dysfunction a risk factor for dementia? A cohort follow-up study. Br J Anaesth. 2013 Jun;110 Suppl 1:i92–7. doi: 10.1093/bja/aes466. Epub 2012 Dec 28.

46. Bilotta F, Gelb WA, Stazi E, et al. Pharmacological perioperative brain neuroprotection: a ualitative review of randomized clinical trials. Br J Anaesth. 2013 Jun;110 Suppl 1:i113–20. doi: 10.1093/bja/aet059. Epub 2013 Apr 5.

47. Овезов АМ, Брагина СВ, Прокошев ПВ. Цитофлавин при тотальной внутривенной анестезии. Вестник хирургии. 2010;169(2):64–7. [Ovezov AM, Bragina SV, Prokoshev PV. Cytoflavin in total intravenous anaesthesia. Vestnik khirurgii. 2010;169(2):64–7. (In Russ.)].

48. Овезов АМ, Лобов МА, Машков АЕ и др. Частота развития и возможность коррекции послеоперационной когнитивной дисфункции у детей школьного возраста при современных вариантах анестезиологического обеспечения. Consilium Medicum. 2013;(2):50–4. [Ovezov AM, Lobov MA, ashkov AE, et al. The incidence and the possibility of correction of postoperative cognitive dysfunction in school-age children in modern versions of anesthetic management. Consilium Medicum. 2013;(2):50–4. (In Russ.)].

49. Овезов АМ, Лобов МА, Надькина ЕД и др. Цитиколин в профилактике послеоперационной когнитивной дисфункции при тотальной внутривенной анестезии. Анналы клинической и экспериментальной неврологии. 2013;7(2):27–34. [Ovezov AM, Lobov MA, Nad'kina ED i dr. Citicoline in the prevention of postoperative cognitive dysfunction during total intravenous anaesthesia. Annaly klinicheskoi i eksperimental'noi nevrologii. 2013;7(2):27–34. (In Russ.)].

50. Thomas J, Crosby G, Drummond JC, Todd M. Anesthetic Neurotoxicity: A Difficult Dragon to Slay. Anesth Analg. 2011 Nov;113(5):969–71. doi: 10.1213/ANE.0b013e318227740b.


For citations:

Ovezov A.M., Knyazev A.V., Panteleeva M.V., Lobov M.A., Borisova M.N., Lugovoy A.V. Postoperative encephalopathy: Pathophysiological and morphological bases of its prevention under general anesthesia. Neurology, Neuropsychiatry, Psychosomatics. 2015;7(2):61-66. (In Russ.)

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