The use of a neurometabolic drug for the prevention of postoperative cognitive dysfunction in elderly patients operated on the lumbosacral spine

The objective was to evaluate the effect of perioperative use of the neurometabolic drug Cytoflavin on the dynamics of biomarkers of brain damage and the relationship of these indicators with the frequency of POCD in elderly patients who underwent surgery on the lumbosacral spine.

Materials and methods. Patients were divided into two groups: patients in the first group were injected with Cytoflavin (solution for intravenous administration) in the perioperative period; in the second group, Cytoflavin was not administered. Patients were surveyed using the Montreal Cognitive Assessment Scale (MoCA) and the National Institutes of Health (NIHSS) Stroke Scale. Transcranial Dopplerography was performed to assess velocity parameters in intracranial arteries. The levels of laboratory parameters in the blood were analyzed: matrix metalloproteinase (MMP-9), brain neurotrophic factor (BDNF), neuron-specific enolase (NSE), protein S-100 (S-100), antibodies to Nmethyl-D-aspartate receptors (NMDAR), C-reactive protein (CRP), lactate, lactate dehydrogenase (LDH). The studies were conducted at several points: 1 – the day before surgery; 2 – intraoperatively at the stage of hemostasis; 3 – the next day after surgery.

Results. There were no significant changes in the MoCA test results. The BDNF level decreased in the intraoperative period, returning to baseline values on the first postoperative day in both study groups. The concentration of NSE increased during surgery, returning to baseline values in the control group and decreased below baseline values in the main group. The S-100 protein increased in the control group on the first postoperative day. Fluctuations in the indicators of markers of brain damage in both study groups did not exceed the reference values.

Conclusion. Perioperative use of Cytoflavin in elderly patients who underwent surgery on the lumbosacral spine had no significant effect on the dynamics of biomarkers of brain damage; no relationship between these indicators and the occurrence of POCD was found based on testing of patients on the MoCA scale.

1. Zykova Yu. V., Evert L. S., Potupchik T. V. Neurotrophic factor of the brain as an indicator of diseases of the central nervous system. Doctor, 2021, vol. 32, no. 4, pp. 5–9. (In Russ.). https://doi.org/10.29296/25877305-2021-04-01.

2. Lugovoy A. V., Panteleeva M. V., Nadkina E. D., Ovezov A. M. Intraoperative prevention of cognitive impairment in total intravenous anesthesia in school-age children: randomized clinical trial. Annals of Critical Care, 2018, no. 4, pp. 57–64. https://doi.org/10.21320/1818-474X-2018-4-57-64.

3. Lyashenko E. A., Ivanova L. G., Chimagomedova A. Sh. Postoperative cognitive disorder. S. S. Korsakov Journal of Neurology and Psychiatry, 2020, vol. 120, no. 10, issue 2, pp. 39–45. (In Russ.). https://doi.org/10.17116/jnevro202012010239.

4. Ovezov A. M., Panteleeva M. V., Knyazev A. V. et al. Cognitive dysfunction and general anesthesia: from pathogenesis to prevention and correction. Neurology, neuropsychiatry, psychosomatics, 2016, vol. 8, no. 3, pp. 101–105. (In Russ.). http://dx.doi.org/10.14412/2074-2711-2016-3-101-105.

5. Orlov Yu. P., Butrov A. V., Sviridov S. V. et al. Succinate and succinate dehydrogenase as a «foothold» in the Krebs cycle in critical conditions. Antibioticsand Chemotherapy, 2023, vol. 68, no. 1–2, pp. 57–68. (In Russ.). https://doi.org/10.37489/0235-29902023-68-1-2-57-68.

6. Polushin A. Yu., Ianishevskiĭ S. N., Maslevtsov D. V. et al. The efficacy of prevention of postoperative cognitive dysfunction in cardiac surgeries with the use of the cerebrolysin. S. S. Korsakov Journal of Neurology and Psychiatry, 2017, vol. 117, no. 12, pp. 37–45. (In Russ.). https://doi.org/10.17116/jnevro201711712137-45.

7. Bricourt M. O., Ghnassia M. D., Legout-Montdargent V. Améliorationpar la CDP-choline de la récupération post-opératoire de sujets à risquecérébral [CDP-choline improves the postoperative rehabilitation of patients with cerebral risk]. Agressologie, 1990, vol. 31, no. 7, pp. 457–463.

8. Cuzner M. L., Opdenakker G. Plasminogen activators and matrix metalloproteases, mediators of extracellular proteolysis in inflammatory demyelination of the central nervous system. J Neuroimmunol, 1999, vol. 94, no. 1–2, pp. 1–14. https://doi.org/10.1016/s0165-5728(98)00241-0.

9. Dingledine R., Borges K., Bowie D. et al. The glutamate receptor ion channels. Pharmacol Rev, 1999, vol. 51, no. 1, pp. 7–61. PMID: 10049997.

10. Khodorov B. Glutamate-induced deregulation of calcium homeostasis and mitochondrial dysfunction in mammalian central neurons. ProgBiophysMol Biol, 2004, vol. 86, no. 2, pp. 279–351. https://doi.org/10.1016/j.pbiomolbio.2003.10.002.

11. Lin X., Chen Y., Zhang P. et al. The potential mechanism of postoperative cognitive dysfunction in older people. Exp Gerontol, 2020, vol. 130, pp. 110791. https://doi.org/10.1016/j.exger.2019.110791.

12. Leslie M. The post-op brain. Science, 2017, vol. 356, pp. 898–900. https://doi.org/10.1126/science.356.6341.898

13. Rasmussen L. S., Larsen K., Houx P. et al. The assessment of postoperative cognitive function. ActaAnaesthesiolScand, 2001, vol. 45, no. 3, pp. 275–289.

14. Rundshagen I. Postoperative cognitive dysfunction. DtschArztebl Int, 2014, vol. 111, no. 8, pp. 119–125. https://doi.org/10.3238/arztebl.2014.0119.

15. Terrando N., Eriksson L. I., Ryu J. K. et al. Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol, 2011, vol. 70, no. 6, pp. 986–995. https://doi.org/10.1002/ana.22664.

16. Vacas S., Degos V., Feng X. et al. The neuroinflammatory response of postoperative cognitive decline. Br Med Bull, 2013, vol. 106, pp. 161–178. https://doi.org/10.1093/bmb/ldt006.

17. Wei P., Yang F., Zheng Q. et al. The potential role of the NLRP3 inflammasome activation as a link between mitochondria ROS generation and neuroinflammation in postoperative cognitive dysfunction. Front Cell Neurosci, 2019, vol. 13, pp. 73. https://doi.org/10.3389/fncel.2019.00073.

18. Yang Y., Liu Y., Zhu J. et al. Neuroinflammation-mediated mitochondrial dysregulation involved in postoperative cognitive dysfunction. Free Radic Biol Med, 2022, vol. 178, pp. 134–146. https://doi.org/10.1016/j.freeradbiomed.2021.12.004.

19. Yin C., Gou L. S., Liu Y. et al. Repeated administration of propofolupregulated the expression of c-Fos and cleaved-caspase-3 proteins in the developing mouse brain. Indian J. Pharmacol, 2011, vol. 43, no. 6, pp. 648–651. https://doi.org/10.4103/0253-7613.89819.