PLACE OF PRESEPSIN IN THE SCREENING FOR INFECTIONS IN THE CRITICALLY ILL PATIENTS

In the patients staying in the intensive care wards, it is often necessary to differentiate the cause of systemic inflammatory response and multiple organ failure (infectious and non-infectious cause), which is often impossible unless various biomarkers are used.

The objective: to study the informativeness of presepsin versus traditional biomarkers (procalcitonin, C-reactive protein), to find benefits and drawbacks of these biomarkers when investigating the nature of the systemic inflammatory response in critical states of various etiology.

Subjects and methods. The retrospective-prospective study trail was conducted. 95 patients were included into the trial, they all were admitted to intensive care wards with symptoms of systemic inflammatory response and multiple organ failure, assessed as 2 and more SOFA scores and who had their levels of procalcitonin, presepsin and C-reactive protein tested. In order to assess sensitivity and specificity of presepsin for diagnostics of infections in the patients with disorders of excretory function of the kidneys and those with neutropenia, and the patients after massive traumatic surgeries, the following categories of patients were prospectively included in the study: patients with chronic kidney disease receiving hemodialysis (n=17), those with oncohematological disorders (n=8), and patients undergoing cardiac surgery (n=20) with cardiopulmonary bypass and without it (of pump).

Results. It was demonstrated that presepsin was more sensitive and specific for diagnostics of sepsis versus other investigated biomarkers. It was found out that in the patients with sepsis and disorders of excretory function of the kidneys, the level of presepsin (IU 10 876 (2 030; 15 972) was nearly 8 times higher than in the patients receiving no substitutive renal therapy with hemodialysis Patients with neutropenia (IU of white blood count ‒ 0.4 (0.3; 0.5) and infectious complications had the level of presepsin compatible with the one in the patients undergoing surgery with no neutropenia: IU of presepsin in the patients with local infection made 324 (191; 601) pg/ml, and in the patients with sepsis it made 3,176 (1,514‒4,837) pg/ml. During the peri-operative period, the changes in the biomarkers level in the patients undergoing cardiac surgery demonstrated that their level significantly increases in 12 hours after surgery versus pre-operative level, despite the absence of the systemic infection. And the fold of procalcitonin increase (22-fold rise) was much higher versus presepsin (3-fold rise). The tendency to normalization of presepsin level was observed in 24 hours, the fact of cardiopulmonary bypass provided no significant impact on the changes in presepsin level.

Conclusion. As an infection biomarker, presepsin possesses high sensitivity and specificity. It can be used for diagnostics of infection in the patients with neutropenia and without it. But it should be noted that its level can be increased in case of a critical state not related to the development of infectious complications. When interpreting the obtained clinical data it is important to understand which mechanisms can cause the elevation of its level in blood in a certain situation. For the most difficult cases, the most adequate result can be obtained when the levels of different biomarkers are tested simultaneously.

1. Velkov V.V. Presepsin is a new highly effective biomarker of sepsis. Kliniko-laboratorny Konsilium. Nauch. Prakt. Journal, 2012, vol. 2, no. 42, pp. 56-62. (In Russ.)

2. Velkov V.V. Procalcitonin and C-reactive protein in the modern laboratory diagnostics. Part 1. Kliniko-laboratorny Konsilium. Nauch. Prakt. Journal, 2008, vol. 6, no. 25, pp. 46-52. (In Russ.)

3. Gelfand B.R., Burnevich S.Z., Gelfand E.B., Brazhnik T.B., Sergeeva N.А. Biochemical markers of system inflammation response: role of procalcitoni in the diagnostics of sepsis. Infeksii v Khirurgii, 2007, vol. 5, no. 1, pp. 19-24. (In Russ.)

4. Plyusch M.G., Rogalskaya E.А., Samsonova N.N. et al. Informativeness of presepsin level for stratification of risk in the patients after cardiac and vascular surgery. Laboratoriya, 2014, vol. 2, no. 49. (In Russ.)

5. Polushin Yu.S., Аfanasiev А.А., Malyshev M.Yu., Pivovarova L.P. Changes of procalcitonin level in the post-traumatic period and its role in systemic response to trauma. Vestnik Anasteziol. i Reanimatol., 2017, vol. 14, no. 2, pp. 5-13. (In Russ.)

6. Polushin Yu.S., Аfanasiev А.А., Malyshev M.Yu., Pivovarova L.P. Clinical and diagnostic value of procalcitonin level in those suffering with severe concurrent trauma. Vestnik Anasteziol. i Reanimatol., 2015, vol. 12, no. 1, pp. 46-54. (In Russ.)

7. Polyakova I.N., Аndrosova M.V., Mazanov M.Kh., Godkov M.А. Changes in presepsin blood level in the patients with ischemic heart disease who had surgery with cardiopulmonary bypass. VII Nauchno-prakticheskaya konferentisya Sovremennye tekhnologii i metody diagnostiki razlichnykh grupp zabolevany, laboratorny analiz. [The VlIth Scientific Practical Conference on Modern Technology and Methods for Diagnostics of Various Diseases, Laboratory Testing]. Moscow, 2014.

8. Popov D.А., Plyusch M.G., Ovseenko S.T. et al. Monitoring of SCD14-ST (presepsin) level in pre-operative period in the patients undergoing cardiac surgery. Anesteziol. i Reanimatol., 2013, vol. 3, pp. 30-35. (In Russ.)

9. Rudnov V.A. Sepsis: modern approaches to diagnostics and intensive therapy (part one). Vestnik Anasteziol. i Reanimatol., 2010, no. 1, pp. 48-57. (In Russ.)

10. Sepsis v nachale XXI v. Klassifikatsiya, kliniko-diagnosticheskaya kontseptiya i lecheniye. Patologoanatomicheskaya diagnostika. [Sepsis in early XXI cen. Classification, clinical and diagnostic concept and treatment. Postmortem diagnostics]. V.S. Saveliev, B.R. Gelfand, eds. Moscow, Litterra Publ., 2006, 176 p.

11. Shlyk I.V. Patogenez, rannyaya diagnostika i printsipy lecheniya sepsisa u tyazheloobozhzhennykh. Diss. dokt. med, nauk. [Sepsis pathogenesis, early diagnostics and treatment in those with severe burns. Doct. Diss.]. 14.01.20, St. Petersburg, 2009, 268 p.

12. Arai Y., Mizugishi K., Nonomura K., Naitoh K., Takaori-Kondo A., Yamashita K. Phagocytosis by human monocytes is required for the secretion of presepsin. J. Infect. Chemother., 2015, vol. 21, no. 8, pp. 564-569.

13. Benoist J.F., Mimoz O., Assicot M. Procalcitonin in severe trauma. Ann. Biol. Clin. (Paris), 1998, vol. 56, no. 5, pp. 571-574.

14. Bommer J., Weinreich T., Lovett D.H. et al. Particles from dialysis tubing stimulate interleukin – 1 secretion by macrophage. Nephrology Dialysis Transplantation, 1990, vol. 5, pp. 208-213.

15. Bone R.C., Balk R.A., Cerra F.B., Dellinger R.P., Fein A.M., Knaus W.A., Schein R.M., Sibbald W.J. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest, 1992, vol. 101, no. 6, pp. 1644-1655.

16. Carracedo J., Ramirez R., Pintado O. et al. Cell aggregation and apoptosis induced by hemodialysis membranes. J. Am. Soc. Nephrol., 1995, vol. 6, pp. 1586-1591.

17. Churpek M.M., Zadravecz F.J., Winslow C., Howell M.D., Edelson D.P. Incidence and prognostic value of the systemic inflammatory response syndrome and organ dysfunctions in ward patients. Am. J. Respir. Crit. Care Med., 2015, vol. 192, pp. 958-964.

18. Descamps-Latscha B., Goldfarb B., Nguyen A.T. et al. Etablishing the relationship between complement activation and stimulation of phagocyte oxidative metabolism in hemodialyzed patients a randomized prospective study. Nephron., 1991, vol. 59, pp. 279-285.

19. Dornbusch H.J., Strenger V., Sovinz P., Lackner H., Schwinger W., Kerbl R., Urban C. Non-infectious causes of elevated procalcitonin and C-reactive protein serum levels in pediatric patients with hematologic and oncologic disorders. Support Care Cancer, 2008, vol. 16, no. 9, pp. 1035-1040.

20. Downing G., Biomarkers Definitions Working Group. Biomarkers and Surrogate Endpoints. Clinical Pharmacology & Therapeutics, 2001, vol. 69, pp. 89-95.

21. Grace E., Mackenzie Turner R. Use of procalcitonin in patients with various degrees of chronic kidney disease including renal replacement therapy. Clin. Infecti. Diseases, 2014, vol. 59, no. 12, pp. 1761-1767.

22. Himmelfarb J., MacMonagle E., Holbrook D., Toth C. Soluble complement receptor 1 inhibits both complement and granulocyte activation during ex vivo hemodialysis. J. Lab. Clin. Med., 1995, vol. 126, pp. 392-400.

23. Kubatiev A., Rudko I., Ermolenko V. Complement activation and neutrophil aggregation changes during haemodialysis. Int. J. Clin. Pharmacol. Res., 1993, vol. 13, pp. 293-299.

24. Lucchi I., Bonucchi D., Acerbi M.A. et al. Improved biocompatibility by modified cellulosis membranes: the case of hemofan. Artif. Organs, 1989, vol. 13, pp. 417-421.

25. Makarova P., Galstyan G., Krechetova A. Usefulness of presepsin (PSP) for assessment of sepsis in leukopeniс patients (pts). Abstr. 27th Annual Congress, ESICM LIVES 2014, Barcelona, Spain, 27 September –1 October 2014. Crit. Care, 2014.

26. Marshall J.C., Vincent J.L., Fink M.P., Cook D.J., Rubenfeld G., Foster D. et al. Measures, markers, and mediators: toward a staging system for clinical sepsis. A report of the Fifth Toronto Sepsis Roundtable, Toronto, Ontario, Canada, October 25–26, 2000. Crit. Care Med., 2003, vol. 31, no. 5, pp. 1560-1567.

27. Marshall J.C., Reinhart K. Biomarkers of sepsis. Crit. Care Med., 2009, vol. 37, no. 7, pp. 2290-2298.

28. Maurice M., Nafea D., Sawy M., Soelam R., Youssef S. Usefulness of presepsin (soluble CD14 subtype) as a diagnostic marker of sepsis in Egyptian patients with acute myeloid leukemia. Am. J. Molec. Biology, 2014, vol. 4, pp. 169-176.

29. Mokart D. et al. Procalcitonin, interleukin 6 and systemic inflammatory response syndrome (SIRS): early markers of postoperative sepsis after major surgery. Brit. J. Anaesthesia, 2005, vol. 94, no. 6, pp. 767-773.

30. Moore L.J., Moore F.A., Todd S.R. et al. Sepsis in general surgery: the 2005–2007 national surgical quality improvement program perspective. Arch. Surg., 2010, vol. 145, no. 7, pp. 695-700.

31. Nakamura Y., Ishikura H., Nishida T. et al. Usefulness of presepsin in the diagnosis of sepsis in patients with or without acute kidney injury. BMC Anesthesiol., 2014, vol. 14, no. 8.

32. Namas R., Zamora R., Namas R. et al. Sepsis: Something old, something new, and a systems view. J. Crit. Care, 2012, vol. 27, no. 3, pp. 314.

33. Pierrakos C., Vincent J.L. Sepsis biomarkers: a review. Crit. Care, 2010, vol. 14, no. 1, pp. 2-18.

34. Ramana K.V., Pinnelli V.B.K., Kandi S., Asha G., Jayashankar C.A., Bhanuprakash, Raghavendra D.S., Sanjeev D. Presepsin: a novel and potential diagnostic biomarker for sepsis. Am. J. Med. Biol. Research, 2014, vol. 2, no. 4, pp. 97-100.

35. Saito J. et al. Changes in presepsin concentrations in surgical patients with end-stage kidney disease undergoing living kidney transplantation: a pilot study. J. Anesth., 2015, vol. 30, no. 1, pp. 174-177.

36. Schneider H.G., Lam Q.T. Procalcitonin for the clinical laboratory: a review. Pathology, 2007, vol. 39, no. 4, pp. 383-390.

37. Singer M. et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 2016, vol. 315, no. 8, pp. 801-810. (In Russ.)

38. Skroeder N.R., Kjellstrand P., Holmquist B., Nillson U., Jacobson S.H. Increased amounts of C3a and the terminal complement complex at high dialysis blood-flow: the relation with dialysis efficiency. Nepfron, 1996, vol. 72, pp. 523-529.

39. Uzzan B., Cohen R., Nicolas P., Cucherat M., Perret G. Y. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Crit. Care Med., 2006, vol. 34, pp. 1996-2003.

40. Wanner G.A. et al. Relationship between procalcitonin plasma levels and severity of injury, sepsis, organ failure, and mortality in injured patients. Critical Care Medicine-Baltimore, 2000, vol. 28, no. 4, pp. 950-957.

41. Warren O.J., Smith A. J., Alexiou C., Rogers P.L., Jawad N., Vincent C., Darzi A.W., Athanasiou T. The inflammatory response to cardiopulmonary bypass: part 1 – mechanisms of pathogenesis. J. Cardiothorac. Vasc. Anesth., 2009, vol. 23, no. 2, pp. 223-231.

42. Wojtaszek M. et al. Changes of procalcitonin level in multiple trauma patients. Anaesthesiol. Int. Ther., 2014, vol. 46, no. 2, pp. 78-82.