Influence of Sedation with Dexmedetomidine on Oxidative Distress During Delirium Developed Following Severe Polytrauma

Purpose is to evaluate the influence of intravenous sedation with dexmedetomidine and propofol on the intensity of oxidative distress, delirium severity and duration in severe polytrauma patients.

Material and methods. 100 victims (18 to 50 years of age, trauma of two regions and more, ISS score at admission equal to 16–50) were included in the study. Depending on sedation method, the patients were split into group I (n=51) and group II (n=49), in the combined therapy of whom propofol and dexmedetomidine were used, respectively. In addition to standard examinations, the blood plasma carbonylated peptides were assayed in all patients.

Results. It has been established that the assay content of carbonylated peptides in blood might reflect polytrauma severity. A link between the oxidative distress intensity and delirium duration (r=0.34; P<0.05) and severity (r=0.38, P<0.05) in severe polytrauma patients has been demonstrated, which might support the role of oxidative distress in delirium development. Influence of the sedation drugs dexmedetomidine or propofol on oxidative distress intensity was not evident in all stages of the study.

Conclusion. Significant oxidative distress promotes longer and more severe course of delirium in severe polytrauma patients. The content of carbonylated proteins over 0.78 nmol/mg predicts the development of cognitive dysfunction one month after severe polytrauma with 62% sensitivity and 67% specificity. In spite of clinical efficacy, neither dexmedetomidine nor propofol reliably reduce oxidative distress in severe polytrauma patients.

1. Kichin V.V., Likhvancev V.V., Bolshedvorov R.V., Ryabov S.V., Sungurov V.A. Selected issues of anesthesia and intensive care of severe concomitant injury. Moscow: Border (Granitsa); 2010: 312. [In Russ.]

2. Rezepov N.A., Skripkin Y.V., Ulitkina O.N., Grebenchikov O.A., Likhvantsev V.V. Predictors of the Severity and Duration of Treatment of Sepsis-Associated Delirium. Obshchaya reanimatologiya=General Reanimatology. 2017; 13 (6): 28–37. [In Russ., In Engl.] DOI: 10.15360/1813-9779-2017-6-28-37

3. Vereshchagin E.I., Mitrofanov I.M., Samatov I.Y., Streltsova E.I., Veinberg A.L., Potter E.A., Bogachov S.S. Nucleic Acid Metabolism in Patients with Severe Burn Injury and the Possibility of Its Correction. Obshchaya reanimatologiya=General Reanimatology. 2019; 15 (1): 4–11. [In Russ., In Engl.] DOI: 10.15360/1813-9779-2019-1-4-11

4. Li Y., Yu Z.X., Ji M.S., Yan J., Cai Y., Liu J., Yang H.F., Jin Z.C. A Pilot Study of the Use of Dexmedetomidine for the Control of Delirium by Reducing the Serum Concentrations of Brain-Derived Neurotrophic Factor, Neuron-Specific Enolase, and S100B in Polytrauma Patients. Journal of Intensive Care Medicine. 2017; 1: 8. PMID: 28569132. DOI: 10.1177/0885066617710643

5. Fineberg S., Nandyala S., Marquez-Lara A., Oglesby M., Patel A., Singh K. Incidence and risk factors for postoperative delirium after lumbar spine surgery. Spine (Phila Pa 1976). 2013; 38 (20): 1790–1796. PMID: 23797502. DOI: 10.1097/BRS.0b013e3182a0d507

6. Bellelli G., Mazzola P., Morandi A., Bruni A., Carnevali L., Corsi M., Zatti G., Zambon A., Corrao G., Olofsson B., Gustafson Y., Annoni G. Duration of postoperative delirium is an independent predictor of 6month mortality in older adults after hip fracture. J. Am. Geriatr. Soc.. 2014; 2 (7): 1335–1340. PMID: 24890941. DOI: 10.1111/jgs.12885

7. Aldecoa C., Bettelli G., Bilotta F., Sanders R., Audisio R., Borozdina A., Cherubini A., Jones C., Kehlet H., MacLullich A., Radtke F., Riese F., Slooter A.J., Veyckemans F., Kramer S., Neuner B., Weiss B., Spies C.D. European Society of Anaesthesiology evidence-based and consensus based guideline on postoperative delirium. Eur. J. Anaesthesiol. 2017; 34 (4): 192–214. PMID: 28187050. DOI: 10.1097/EJA.0000000000000594

8. Bickel H., Gradinger R., Kochs E., Forstl H. High risk of cognitive and functional decline after postoperative delirium. A three-year prospective study. Dement. Geriatr. Cogn. Disord.. 2008; 26 (1): 26–31. PMID: 18577850. DOI: 10.1159/000140804

9. Lihvancev V.V. Nonspecific delirium in the intensive care unit. Anesteziol. Reanimatol. 2015; 60 (2): 55–59 [In Russ.]

10. Descamps L., Coisne C., Dehouck B., Cecchelli R., Torpier G. Protective effect of glial cells against lipopolysaccharide-mediated blood-brain barrier injury. Glia. 2003; 42: 46–58. PMID: 12594736. DOI: 10.1002/glia.10205

11. Alexander J.J., Jacob A., Cunningham P., Hensley L., Quigg R.J. TNF is a key mediator of septic encephalopathy acting through its receptor, TNF receptor-1. Neurochem Int. 2008; 52: 447–456. PMID: 17884256. DOI: 10.1016/j.neuint.2007.08.006

12. Hughes C.G., Patel M.B., Pandharipande P.P. Pathophysiology of acute brain dysfunction: what’s the cause of all this confusion? Curr Opin Crit Care. 2012; 18: 518–526. PMID: 22941208. DOI: 10.1097/MCC.0b013e328357effa

13. Vorobjeva N., Prikhodko A., Galkin I., Pletjushkina O., Zinovkin R., Sud’ina G., Chernyak B., Pinegin B. Mitochondrial reactive oxygen species are involved in chemoattractant-induced oxidative burst and degranulation of human neutrophils in vitro. European Journal of Cell Biology. 96 (3): 254–265. PMID: 28325500. DOI: 10.1016/j.ejcb.2017.03.003

14. American Geriatrics Society Expert Panel on Postoperative Delirium in Older Adults Postoperative delirium in older adults: best practice statement from the American Geriatrics Society.// J. Am. Coll. Surg. 2015; 220 (2): 136–148. PMID: 25535170. DOI: 10.1016/j.jamcollsurg.2014.10.019

15. Yao W., Luo G., Zhu G., Chi X., Zhang A., Xia Z., Hei Z. Propofol activation of the Nrf2 pathway is associated with amelioration of acute lung injury in a rat liver transplantation model. Oxid Med Cell Longev. 2014: 258–567. PMID: 24669282. DOI: 10.1155/2014/258567

16. Lee S., Kim K., Kim Y.H., Chung M.H., Kang I., Ha J., Choe W. Preventive role of propofol in hypoxia/reoxygenation-induced apoptotic H9c2 rat cardiac myoblast cell death. Mol Med Rep. 2011; 4 (2): 351–356. PMID: 21468576.

17. Si Y.N., Bao H.G.,, Xu L., Wang X.L., Shen Y., Wang J.S., Yang X.B. Dexmedetomidine protects against ischemia/reperfusion injury in rat kidney. Eur. Rev. Med. Pharmacol. Sci. 2014; 18 (13): 1843–1855. PMID: 25010612

18. Ulitkina O.N., Grebenchikov O.A., Skripkin Yu.V., Bershadskij F.F. Organoprotective properties of dexmedetomidine. Vestn. Anesteziol. Reanimatol.2018; 15 (2): 54–60. [In Russ.] DOI: 10.21292/2078-56582018-15-2-54-60

19. Kip G., Celik A., Bilge M., Alkan M., Kiraz H.A., Ozer A., Tyvgyn V., Erdem O., Arslan M., Kavutcu M. Dexmedetomidine protects from postmyocardial ischaemia reperfusion lung damage in diabetic rats. Libyan J Med. 2015; 10: 10. PMID: 26387799. DOI: 10.3402/ljm.v10.27828

20. Chen S., Hua F., Lu J., Jiang Y., Tang Y., Tao L., Zou B., Wu Q. Effect of dexmedetomidine on myocardial ischemia-reperfusion injury. Int J Clin Exp Med. 2015; 8 (11): 21166–21172. PMID: 26885050

21. Association for Automotive Medicine. The Abbreviated Injury Scale 2005: Des Plaines; 2008: 167.

22. Baker S., O’Neill B., Haddon W., Long W. The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J. Trauma. 1974; 14 (3): 187-196. PMID: 4814394

23. Gelfand B.R., Saltanov A.I. Intensive therapy: national guideline. М.: GEOTAR-Media; 2011: 984. [In Russ.]

24. Mock C. Guidelines for essential trauma care. Geneva: World Health Organization, 2004: 94.

25. Ely E., Margolin R., Francis J., May L., Truman B., Dittus R., Speroff T., Gautam S., Bernard G.R., Inouye S.K. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit. Care Med. 2001; 29 (7): 1370–1379. PMID: 11445689

26. Bergeron N., Dubois M., Dumont M., Dial S., Skrobik Y. Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med. 2001; 27 (5): 859–864. PMID: 11430542

27. Sessler C., Gosnell M., Grap M., Brophy G., O’Neal P., Keane K., Tesoro E.P., Elswick R.K. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am. J. Respir. Crit. Care Med. 2002; 166 (10): 1338–1344. PMID: 12421743. DOI: 10.1164/rccm.2107138

28. Fomina M.A., Abalenihina Yu.V. The method of comprehensive assessment of the content of products of oxidative modification of proteins in tissues and biological fluids. Ryazan: Ryazan State Medical University. 2014: 60. [In Russ.]

29. Levine R., Williams J., Stadtman E., Shacter E. Carbonyl assays for determination of oxidatively modified proteins. Methods Enzymol. 1994; 233: 346–357. PMID: 8015469

30. Le Gall J., Lemeshow S., Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993; 270 (24): 2957–2963. PMID: 8254858

31. Bershadskij F.F., Ulitkina O.N., Skripkin Yu.V., Lihvancev V.V. Factors determining clinical outcomes in patients with severe combined trauma complicated by delirium. Almanakh klinicheskoj mediciny. 2017; 14 (6): 37–43. [In Russ.] DOI: 10.21292/2078-5658-2017-146-37-43

32. Filippovskaya Zр.S., Gerasimenko O.N., Grebenchikov O.A., Zinovkin R.A., Larkov R.N., Ulitkina O.N., Skripkin Yu.V., Lihvancev V.V. Oxidative stress and early complications of post-surgery complications in cardiosurgery Vestnik anesteziologii i reanimatologii.2016; 13 (6): 13–21. [In Russ.]