The effect of postoperative anesthesia on cognitive impairment in patients

The study of the problem of postoperative cognitive impairment arose from the first moment of anesthesia usage. Over the long history of observations, enough clinical information has been accumulated, however, sometimes it is contradictory and difficult to understand. In most cases, the connection between the fact of surgical intervention with the use of anesthesia and a slowdown in neurocognitive recovery in patients has been confi rmed. There is still an ongoing debate about whether the effects on cognitive abilities can be explained either by the anesthetics themselves or by other factors.

The aim of the work is to use a narrative review to study modern ideas about the effect of anesthesia on the occurrence of cognitive impairment and the further development of cognitive dysfunctions.

Material and methods. To analyze the literature, sources from the international databases Web of Science, Scopus, PubMed, as well as the national library system eLibrary were used.

Results and discussion. The review made it possible to collect the results of long-term clinical observations, as well as experimental studies. Several hypotheses have been put forward about the potential mechanisms triggering the occurrence and development of postoperative cognitive disorders, commonly referred to as postoperative cognitive dysfunction. In particular, special attention was paid to changes in the content of Aß- and Tau-protein substances, increased immunological markers of inflammation, impaired regulation of calcium, and mitochondrial dysfunction. All these mechanisms cannot be considered separately. It represents a complex of interrelated, consistent phenomena. Due to the increasing prevalence of various forms of dementia among the population, there is a need to solve the problem of a deeper study of potential factors affecting postoperative cognitive impairment.

Conclusions. Contemporary researchers are faced with the task of further studying the risk factors of postoperative cognitive impairment, their systematization, development and implementation in clinical practice. New methods of anesthesia in surgical interventions involve the modernization of techniques that reduce the potential risk of cognitive dysfunction.

1. Tsoy R.T., Turuspekova S.T., Klipitskaya N.K. Modern state of the problem of the prevalence of mild cognitive impairment and dementia. Neurosurgery and Neurology of Kazakhstan. 2018;1(50):47-53. (In Russian)].

2. Nichols E., Steinmetz J.D., Vollset S.E. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet. 2022;7(2):E105–E125. DOI:10.1016/S2468-2667(21)00249-8

3. Litvinenko I.V., Lobzin V.Yu. A new paradigm for the development of neurodegenerative diseases on the example of Alzheimer’s disease and Parkinson’s disease. Advances in Gerontology. 2022;35(2):263–273. (In Russian)]. DOI: 10.34922/AE.2022.35.2.010

4. Möllers T., Stocker H., Wei W. Length of hospital stay and dementia: a systematic review of observational studies. Int. J. Geriatr. Psychiatry. 2018;34:8–21. DOI: 10.1002/gps.4993

5. Sharipov R.А., Chelpanov P.N. Early postoperative cognitive dysfunctions in advanced reconstructive-plastic surgery performed under long-term combined multicomponent anesthesia. Practical medicine. 2014;78(2):115–118. (In Russian)].

6. Belova A.N., Prusakova Z.B., Zagrekov V.I. Alzheimer’s disease and anesthesia. Advances in current natural sciences. 2015;8:7–13. (In Russian)].

7. Bedford P.D. Adverse cerebral eff ects of anaesthesia on old people. Lancet. 1955;269:259–263. DOI: 10.1016/s0140-6736(55)92689-1

8. Symes E., Maruff P., Ajani A. Issues associated with the identifi cation of cognitive change following coronary artery bypass grafting. Aust. N. Z. J. Psychiatry. 2000;34:770–784. DOI: 10.1080/j.1440-1614.2000.00808.x

9. Lewis M., Maruff P., Silbert B. Statistical and conceptual issues in defi ning postoperative cognitive dysfunction. Neurosci. Biobehav. Rev. 2004;28:433–440. DOI: 10.1016/j.neubiorev.2004.05.002

10. Ermokhina N.V., Kuzovlev A.N., Polyakov P.A. Early postoperative cognitive impairment after trauma surgery: a prospective cohort study. Russian Journal of Anesthesiology and Reanimatology. 2024;(1):14-22. (In Russian)]. DOI: 10.17116/anaesthesiology202401114

11. Newman S., Klinger L., Venn G. Subjective reports of cognition in relation to assessed cognitive performance following coronary artery bypass surgery. J. Psychosom. Res. 1989;33:227–233. DOI: 10.1016/0022-3999(89)90050-0

12. Evered L., Silbert B., Knopman D.S., Recommendations for the nomenclature of cognitive change associated with Anaesthesia and Surgery-20181. J. Alzheimers Dis. 2018;66:1–10. DOI: 10.3233/JAD-189004

13. Chernykh O.A., Lakhin R.E., Shchegolev A.V. Comparison of the eff ect of combined general and regional anesthesia on the cognitive functions of women of reproductive age: retrospective observational study. Regional Anesthesia and Acute Pain Management. 2023;17(2):115–123. (In Russian)]. DOI: 10.17816/RA321363

14. Bhushan S., Huang X., Duan Y. The impact of regional versus general anesthesia on postoperative neurocognitive outcomes in elderly patients undergoing hip fracture surgery: A systematic review and meta-analysis. Int. J. Surg. 2022;105:106854. DOI: 10.1016/j.ijsu.2022.106854

15. Avdey G., Zhuk I., Makalovich Ya. Psycho-emotional and cognitive disorders in patients after noncardio-surgery operations depending on the type of anesthesia. Psychiatry, Psychotherapy and Clinical Psychology. 2017;8(4):506–515. (In Russian)].

16. Lu X., Jin X., Yang S., Xia Y. The correlation of the depth of anesthesia and postoperative cognitive impairment: a meta-analysis based on randomized controlled trials. J. Clin. Anesth. 2018;45:55– 59. DOI: 10.1016/j.jclinane.2017.12.002

17. Zozulya M.V., Lenkin A.I., Kurapeev I.S. Postoperative cognitive disorders: the pathogenesis, methods of prevention and treatment (literature review). Russian Journal of Anaesthesiology and Reanimatology. 2019;3:25–33. (In Russian)]. DOI: 10.17116/anaesthesiology201903125

18. Paolin A., Michielon P., Betetto M. Lower perfusion pressure during hypothermic cardiopulmonary bypass is associated with decreased cerebral blood fl ow and impaired memory performance 6 months postoperatively. Heart Surg. Forum. 2010;13:E7–12. DOI: 10.1532/HSF98.20091122

19. Kadoi Y., Kawauchi C., Kuroda M. Association between cerebrovascular carbon dioxide reactivity and postoperative short-term and long-term cognitive dysfunction in patients with diabetes mellitus. J. Anesth. 2011;25:641–647. DOI: 10.1007/s00540-011-1182-8

20. Shoair O.A., Grasso M.P., Lahaye L.A. Incidence and risk factors for postoperative cognitive dysfunction in older adults undergoing major noncardiac surgery: a prospective study. J. Anaesthesiol. Clin. Pharmacol. 2015;31:30–36. DOI: 10.4103/0970-9185.150530

21. Fantalis D., Bordovsky S.P., Preobrazhenskaya I.S. Cognitive and emotional disorders in neurosurgical patients and their impact on postoperative rehabilitation. S.S. Korsakov Journal of Neurology and Psychiatry. 2022;122(2):81–87. (In Russian)]. DOI: 10.17116/jnevro202212202181

22. Jiang J., Dong Y., Huang W. General anesthesia exposure and risk of dementia: a meta-analysis of epidemiological studies. Oncotarget. 2017;8:59628–59637. DOI: 10.18632/oncotarget.19524

23. Kim C.T., Myung W., Lewis M. Exposure to general anesthesia and risk of dementia: a Nationwide population-based cohort study. J. Alzheimers Dis. 2018;63:395–405. DOI: 10.3233/JAD-170951

24. Di Nino G., Adversi M., Samolsky Dekel B.G. Peri-operative risk management in patients with Alzheimer’s disease. J. Alzheimers Dis. 2010;22(Suppl 3):121–127. DOI: 10.3233/JAD-2010-101299

25. Baruah J., Easby J., Kessell G. Eff ects of acetylcholinesterase inhibitor therapy for Alzheimer’s disease on neuromuscular block. Br. J. Anaesth. 2008;100:420. DOI: 10.1093/bja/aen010

26. Crowe S., Collins L. Suxamethonium and donepezil: a cause of prolonged paralysis. Anesthesiology. 2003;98:574–575. DOI: 10.1097/00000542-200302000-00040

27. Khan M.A., Hossain F.S., Ahmed I. Predictors of early mortality after hip fracture surgery. Int. Orthop. 2013;37:2119–2124. DOI: 10.1007/s00264-013-2068-1

28. Wan Y., Xu J., Ma D. Postoperative impairment of cognitive function in rats: a possible role for cytokine-mediated infl ammation in the hippocampus. Anesthesiology. 2007;106:436–443. DOI: 10.1097/00000542-200703000-00007

29. Kawano T., Yamanaka D., Aoyama B. Involvement of acute neuroinfl ammation in postoperative delirium-like cognitive defi cits in rats. J. Anesth. 2018;32(4):506–517. DOI: 10.1007/s00540-018-2504-x

30. Xu Z., Dong Y., Wang H. Age- dependent postoperative cognitive impairment and Alzheimer-related neuropathology in mice. Sci. Rep. 2014;4. DOI: 10.1038/srep03766

31. Wu J., Zhang M., Li H. BDNF pathway is involved in the protective eff ects of SS-31 on isofl urane-induced cognitive defi cits in aging mice. Behav. Brain Res. 2016;305:115–121. DOI: 10.1016/j.bbr.2016.02.036

32. Callaway J.K., Wood C., Jenkins T.A. Isofl urane in the presence or absence of surgery increases hippocampal cytokines associated with memory defi cits and responses to brain injury in rats. Behav. Brain Res. 2016;303:44–52. DOI: 10.1016/j.bbr.2016.01.032

33. Le Freche H., Brouillette J., Fernandez-Gomez F.-J. Tau phosphorylation and sevofl urane anesthesia: an association to postoperative cognitive impairment. Anesthesiology. 2012;116:779–787. DOI: 10.1097/ALN.0b013e31824be8c7

34. Guo S., Liu L., Wang C. Repeated exposure to sevofl urane impairs the learning and memory of older male rats. Life Sci. 2018;192:75–83. DOI: 10.1016/j.lfs.2017.11.025

35. Tang J.X., Eckenhoff M.F. Anesthetic eff ects in Alzheimer transgenic mouse models. Prog. Neuro-Psychopharmacol. Biol. Psychiatry. 2013;47:167–171. DOI: 10.1016/j.pnpbp.2012.06.007

36. Bianchi S.L., Tran T., Liu C. Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics. Neurobiol. Aging. 2008;29:1002–1010. DOI: 10.1016/j.neurobiolaging.2007.02.009

37. Berger M., Nadler J.W., Friedman A. The eff ect of Propofol versus Isofl urane anesthesia on human cerebrospinal fl uid markers of Alzheimer’s disease: results of a randomized trial. J. Alzheimers Dis. 2016;52:1299–1310. DOI: 10.3233/JAD-151190

38. Pikwer A., Castegren M., Namdar S. Eff ects of surgery and propofolremifentanil total intravenous anesthesia on cerebrospinal fl uid biomarkers of infl ammation, Alzheimer’s disease, and neuronal injury in humans: a cohort study. J. Neuroinfl ammation. 2017;14:193. DOI: 10.1186/s12974-017-0950-2

39. Xie Z., Swain C.A., Ward S.A.P. Preoperative cerebrospinal fl uid β-amyloid/tau ratio and postoperative delirium. Ann. Clin. Transl. Neurol. 2014;1:319–328. DOI: 10.1002/acn3.58

40. Planel E., Richter K.E., Nolan C.E. Anesthesia leads to tau hyperphosphorylation through inhibition of phosphatase activity by hypothermia. J. Neurosci. 2007;27:3090–3097. DOI: 10.1523/JNEUROSCI.4854-06.2007

41. Xiao H., Run X., Cao X. Temperature control can abolish anesthesiainduced tau hyperphosphorylation and partly reverse anesthesiainduced cognitive impairment in old mice. Psychiatry Clin. Neurosci. 2013;67:493–500. DOI: 10.1111/pcn.12091

42. Dong Y., Wu X., Xu Z. Anesthetic isofl urane increases phosphorylated tau levels mediated by caspase activation and Aβ generation. PLoS One. 2012;7:e39386. DOI: 10.1371/journal.pone.0039386

43. Feng C., Liu Y., Yuan Y. Isofl urane anesthesia exacerbates learning and memory impairment in zinc-defi cient APP/PS1 transgenic mice. Neuropharmacology. 2016;111:119–129. DOI: 10.1016/j.neuropharm.2016.08.035

44. Malashenkova I.K., Hailov N.A., Krynskiy S.A. Glutamate dehydrogenase activity in platelets of patients with endogenous psychosis. S.S. Korsakov Journal of Neurology and Psychiatry. 2016;116(3):39–43. (In Russian)]. DOI: 10.17116/jnevro20161163139-43

45. Kline R., Wong E., Haile M. Peri-operative infl ammatory cytokines in plasma of the elderly correlate in prospective study with postoperative changes in cognitive test scores. Int. J. Anesthesiol. Res. 2016;4:313–321. DOI: 10.19070/2332-2780-1600065

46. Cui R-S., Wang K., Wang Z.-L. Sevofl urane anesthesia alters cognitive function by activating infl ammation and cell death in rats. Exp. Ther. Med. 2018;15:4127–4130. DOI: 10.3892/etm.2018.5976

47. Wu X., Lu Y., Dong Y. The inhalation anesthetic isofl urane increases levels of proinfl ammatory cytokine TNF-α, IL-6 and IL-1β. Neurobiol. Aging. 2012;33:1364–1378. DOI: 10.1016/j.neurobiolaging.2010.11.002

48. Miao H., Dong Y., Zhang Y. Anesthetic Isofl urane or Desfl urane Plus Surgery Diff erently Aff ects Cognitive Function in Alzheimer’s Disease Transgenic Mice. Mol. Neurobiol. 2018;55(7):5623–5638. DOI: 10.1007/s12035-017-0787-9

49. Zhang D.-X., Jiang S., Yu L.-N., Zhang F.-J., Zhuang Q., Yan M. The effect of sevofl urane on the cognitive function of rats and its association with the inhibition of synaptic transmission. Int. J. Clin. Exp. Med. 2015;8:20853–20860. eCollection 2015.

50. Zhang G., Dong Y., Zhang B., Ichinose F., Wu X., Culley D.J. Isofl urane-induced caspase-3 activation is dependent on cytosolic calcium and can be attenuated by memantine. J. Neurosci. 2008;28:4551–4560. DOI: 10.1523/JNEUROSCI.5694-07.2008