New approaches to the impact on the pathogenetic links of sepsis

Sepsis is a systemic pathological reaction that arise because of a severe infection. Now, sepsis is considered as one of the most serious diseases and materially expensive nosology’s. For instance, out of 100% of cases of sepsis, only 40% survive. Thus, there is a high mortality rate and a wide prevalence (up to 300 thousand patients with sepsis are registered in Europe), which makes it possible to identify serious problems and the need to improve the clinical approach to the management strategy and tactics of such patients. The number of cases of detection and registration of sepsis has been expanding expansively since the thirties of the last century, and continues to grow dynamically, which obviously requires an improvement in the pathognomonic approach to therapy. The main reasons for the growth of septic conditions are the increasing use of invasive methods in medical practice, the pandemic of diabetes mellitus, the use of cytostatic and immunosuppressants, as well as the increasing number of antibiotic-resistant strains of pathogenic and conditionally pathogenic bacteria, total disruption of mucosal microbiocenoses, unreasonable use of probiotics with production strains containing foci of pathogenicity in patients with primary or secondary immunodeficiencies. Now, the main etiopathogenetic therapy of sepsis remains drugs aimed at the destruction of pathogenic microorganisms. However, based on the pathogenesis of the septic state, it seems effective to search for drugs with new points of application to individual pathogenesis links of the systemic inflammatory response. Today, studies aimed at establishing the effectiveness of influence on any individual links in the pathogenesis of sepsis - inflammatory mediators, have not yet yielded clear results.

1. Kushimoto S., Abe T., Ogura H., Shiraishi A., Saitoh D., Fujishima S., et al. Impact of Body Temperature Abnormalities on the Implementation of Sepsis Bundles and Outcomes in Patients with Severe Sepsis: A Retrospective Sub-Analysis of the Focused Outcome Research on Emergency Care for Acute Respiratory Distress Syndrome, Sepsis and Trauma Study. Critical Care Medicine: 2019;47(5):691-699. doi: 10.1097/CCM.0000000000003688.

2. Singer M., Deutschman C.S., Seymour C.W., Shankar-Hari M., Annane D., Bauer M., et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–810. doi: 10.1001/jama.2016.0287.

3. Hotchkiss R.S., Moldawer L.L., Opal S.M., Reinhart K., Turnbull I.R., Vincent J.L. Sepsis and septic shock. Nat Rev Dis Primers. 2016;(2):16045. doi: 10.1038/nrdp.2016.45.

4. Ranzani O.T., Shankar-Hari M., Harrison D.A., Rabello L.S., Salluh J.I.F., Rowan K.M., Soares M. A Comparison of Mortality From Sepsis in Brazil and England: The Impact of Heterogeneity in General and Sepsis-Specific Patient Characteristics. Crit Care Med. 2019;47(1):76-84. doi: 10.1097/CCM.0000000000003438.

5. Astafieva M.N., Rudnov V.A., Kulаbukhov V.V., Bаgin V.A., Zubаrevа N.A., Tribulev M.A., Mukhаchevа S.Y. QSOFA score for diagnostics of sepsis. Results of the russian multi-center trial of RISES. Vestnik anesteziologii i reanimatologii = Messenger of anesthesiology and resuscitation. 2018;15(4):14-22. (In Russ.) doi: 10.21292/2078-5658-2018-15-4-14-22.

6. Rhee C., Zhang Z., Kadri S.S., Murphy D.J., Martin G.S., Overton E., et al. CDC Prevention Epicenters Program. Sepsis Surveillance Using Adult Sepsis Events Simplified eSOFA Criteria Versus Sepsis-3 Sequential Organ Failure Assessment Criteria. Crit Care Med. 2019;47(3):307-314. doi: 10.1097/CCM.0000000000003521.

7. Meyer N., Harhay M., Small D., Prescott H., Bowles K., Gaieski D., Mikkelsen M., MSCE. Temporal Trends in Incidence, Sepsis-Related Mortality, and Hospital-Based Acute Care After Sepsis Critical Care Medicine. 2018;46(3):354-360. doi: 10.1097/CCM.0000000000002872.

8. Barbash I.J., Davis B., Kahn J.M. National Performance on the Medicare SEP-1 Sepsis Quality Measure. Crit Care Med. 2019;47(8):1026-1032. doi: 10.1097/CCM.0000000000003613.

9. Casserly B., Phillips G.S., Schorr C., Dellinger R.P., Townsend S.R., Osborn T.M., Reinhart K., Selvakumar N., Levy M.M. Lactate Measurements in Sepsis-Induced Tissue Hypoperfusion. Results from the Surviving Sepsis Campaign Database. Crit Care Med. 2015;43(3):567-73. doi: 10.1097/CCM.0000000000000742.

10. Pruinelli L., Westra B.L., Yadav P., Hoff A., Steinbach M., Kumar V., Delaney C.W., Simon G. Delay Within the 3-Hour Surviving Sepsis Campaign Guideline on Mortality for Patients With Severe Sepsis and Septic Shock. Crit Care Med. 2018;46(4):500-505. doi: 10.1097/CCM.0000000000002949.

11. Wong HR. Sepsis Biomarkers. J Pediatr Intensive Care. 2019;8(1):11-16. doi: 10.1055/s-0038-1677537

12. Polushin Yu.S., Shlyk I.V. Commentary of the issue. Will the modern approaches to sepsis managment be implemented in Russia? Vestnik anesteziologii i reanimatologii = Vestnik anesteziologii i reanimatologii. 2015;12(2):3-6. (In Russ.) Available at: https://cyberleninka.ru/article/n/kommentariy-k-nomeru-udastsya-liv-rossii-realizovat-sovremennye-podhody-klecheniyu-sepsisa.

13. Zulkarnaev A.B., Vatazin A.V., Pasov S.A., Podojnicin A.A. Modern concepts of sepsis pathogenesis and perspective approach to its treatment. Al’manakh klinicheskoy meditsiny = Almanac of Clinical Medicine. 2014;(30):91-98. (In Russ.) doi: 10.18786/2072-0505-2014-30-91-98.

14. Zweigner J., Gramm H.J., Singer O.C., Wegscheider K., Schumann R.R. High concentrations of lipopolysaccharide-binding protein in serum of patients with severe sepsis or septic shock inhibit the lipopolysaccharide response in human monocytes. Blood. 2001;98(13):3800–3808. doi: 10.1182/blood.v98.13.3800.

15. Remick D.G., Bolgos G.R., Siddiqui J., Shin J., Nemzek J.A. Six at six: interleukin-6 measured 6 h after the initiation of sepsis predicts mortality over 3 days. Shock. 2002;17(6):463–467. doi: 10.1097/00024382-200206000-00004.

16. Bulava G.V., Shabanov A.K., Nikitina O.V., Kislukina E.V. Dynamics of systemic inflammatory responce markers in patients with urgent conditions depending on the development of sepsis. Zhurnal im. N.V. Sklifosovskogo Neotlozhnaya meditsinskaya pomoshch = Russian Sklifosovsky Journal Emergency medical care. 2018;7(1):13-19. (In Russ.) doi: 10.23934/2223-9022-2018-7-1-13-19.

17. Loktionova I.L., Pokrovskiy M.V., Ragulina V.A., Titareva L.V., Denisuk T.A., Stupakova E.V., Sytnik M.V., Saroyan K.V., Losenok S.A. The status of vascular endothelium function in infectious diseases of various ethiologies. Nauchnye vedomosti BelGU. Seriya: Meditsina. Farmatsiya. = Belgorod State University

18. Scientific Bulletin. Medicine. Pharmacy. 2012;4(123):20-31. (In Russ.) Available at: https://cyberleninka.ru/article/n/sostoyaniefunktsii-sosudistogo-endoteliya-pri-infektsionnoy-patologii-razlichnoy-etiologii.

19. McHale T.M., Garciarena C.D., Fagan R.P., Smith S.G.J., Martin-Loches I., Curley G.F., Fitzpatrick F., Kerrigan S.W. Inhibition of Vascular Endothelial Cell Leak Following Escherichia coli Attachment in an Experimental Model of Sepsis. Crit Care Med. 2018;46(8):e805-e810. doi: 10.1097/CCM.0000000000003219.

20. Salvemini D., Doyle T.M., Cuzzocera S. Superoxide, peroxynitrite and oxidative/nitrative stress in inflammation. Biochem Soc Trans. 2006;34(5):965-70. doi: 10.1042/BST0340965.

21. Ferdinandy P., Schulz R. Nitric oxide, superoxide, and peroxynitrite in myocardial ischaemiareperfusion injury and preconditioning. Br J Pharmacol. 2003;138(4):532–543. doi: 10.1038/sj.bjp.0705080.

22. Vural K.M., Oz M.C., Liao H., Batirel H.F., Pinsky D.J. Membrane stabilization in harvested vein graft storage: effects on adhesion molecule expression and nitric oxide synthesis. Eur J Cardiothorac Surg. 1999;16(2):150-5. doi: 10.1016/s1010-7940(99)00128-1.

23. Jacobi J. Pathophysiology of sepsis. American Journal of Health-System Pharmacy. 2002; 59(1):3–8. doi: 10.1093/ajhp/59.suppl_1.S3.

24. Gomanova L.I., Fokina M.A. Contemporary views of pathogenetic septic shock mechanisms. Ehlektronnoe nauchnoe izdanie al’manakh prostranstvo i vremya = Electronic scientific edition Almanac space and time. 2018;16(3-4). (In Russ.) doi: 10.24411/2227-9490-2018-12072.

25. de Jong H.K., van der Poll T., Wiersinga W.J. The systemic pro-inflammatory response in sepsis. J Innate Immun. 2010;2(5):422-30. doi: 10.1159/000316286.

26. Weiss S.L., Zhang D., Bush J., Graham K., Starr J., Tuluc F., Henrickson S., Kilbaugh T., Deutschman C.S., Murdock D., McGowan F.X. Jr., Becker L., Wallace D.C. Persistent Mitochondrial Dysfunction Linked to Prolonged Organ Dysfunction in Pediatric Sepsis. Crit Care Med. 2019;47(10):1433-1441. doi: 10.1097/CCM.0000000000003931.

27. Higuchi M., Aggarwai B.B., Yeh T.Y. Activation of CPP3-like protease in tumor necrosis factor- induced apoptosis is dependent on mitochondrial function. J. Clin. Invest. 1997;99(7):1751-1758. Available at: http://www.biomedsearch.com/nih/Activation-CPP32-like-protease-in/9120020.html.

28. Kraft B.D., Chen L., Suliman H.B., Piantadosi C.A., Welty-Wolf K.E. Peripheral Blood Mononuclear Cells Demonstrate Mitochondrial Damage Clearance During Sepsis. Crit Care Med. 2019;47(5):651-658. doi: 10.1097/CCM.0000000000003681.

29. Semeraro N., Ammollo C.T., Semeraro F., Colucci M. Coagulopathy of Acute Sepsis. Semin Thromb Hemost. 2015;41(6):650-8. doi: 10.1055/s-0035-1556730.

30. Levi M., Poll Tv. Coagulation in patients with severe sepsis. Semin Thromb Hemost. 2015;41(1):9-15. doi: 10.1055/s-0034-1398376.

31. Gutierez G., Wulf M. Lactic acidosis in sepsis: a commentary. Intensive Care Med. 1996;22(1):6-16. doi: 10.1007/bf01728325.

32. Hotchkiss R.S., Karl I.E. Reevaluation of the role of cellular hypoxia and bioenergetic failure in sepsis. JAMA. 1992;267(11):1503-10. Available at: http://www.biomedsearch.com/nih/Reevaluation-role-cellular-hypoxiabioenergetic/1538541.html.

33. Pushkina T.A., Tokayev E.S., Popova T.S., Borodina E.N. Superoxide dismutase as a component of antioxidant therapy: current state of the issue and prospects (a literature review). Zhurnal im. N.V. Sklifosovskogo Neotlozhnaya meditsinskaya pomoshch = Russian Sklifosovsky Journal Emergency Medical Care. 2016;(4):42-47. (In Russ.) Available at: https://www.jnmp.ru/jour/article/view/321.