Корреляция между повышенным уровнем соотношения нейтрофилов и лимфоцитов, показателем вазотропности и инотропности, суммарным балансом жидкости и уровнем активных форм кислорода у пациентов с сепсисом

Введение. Активные формы кислорода (ROS) служат биомаркером сепсиса, в то время как соотношение нейтрофилов и лимфоцитов (NLR), показатель вазотропно-инотропного действия (VIS) и общий баланс жидкости (CFB) коррелируют с воспалением и смертностью. Понимание корреляции между повышенным уровнем ROS и этими маркерами помогает в прогнозировании.

Цель – изучение корреляции между повышенным уровнем соотношения нейтрофилов и лимфоцитов, показателем вазотропности и инотропности, суммарным балансом жидкости и уровнем активных форм кислорода у пациентов с сепсисом.

Материалы и методы. В проспективном когортном исследовании, проведенном в отделении интенсивной терапии доктора Муварди в RSUD с июня по август 2023 г., использовали одномерный, двумерный (корреляция Спирмена) и многомерный логистический регрессионный анализы.

Результаты. У 34 пациентов с сепсисом выявлена значимая положительная корреляция показателей NLR и VIS в первый день, а показателей NLR, VIS и FB – на третий день. Дельта-изменения показателей NLR и VIS достоверно коррелировали с ROS.

Заключение. изменения NLR и VIS предсказывают уровни ROS, в то время как CFB демонстрирует слабую корреляцию, которая заслуживает дополнительного изучения. Это подчеркивает важность NLR и VIS как прогностических показателей при сепсисе.

1. Cecconi M., Evans L., Levy M., Rhodes A. Sepsis and septic shock. The Lancet, 2018, vol. 392, pp. 75–87. DOI: 10.1016/S0140-6736(18)30696-2.

2. Shetty A., Macdonald S.P.J., Keijzers G., Williams J.M. Review article: Sepsis in the emergency department – Part 2: Investigations and monitoring. Emerg Med Australas, 2018, vol. 30, no. 1, pp. 4–12. DOI: 10.1111/1742-6723.12924.

3. Zhang S., Luan X., Zhang W., Jin Z. Platelet-to-lymphocyte and neutrophil-to-lymphocyte ratio as predictive biomarkers for early-onset neonatal sepsis. Journal of the College of Physicians and Surgeons Pakistan, 2021, vol. 31, pp. 821–824.

4. Gaies M.G., Jeffries H.E., Niebler R.A. et al. Vasoactive-inotropic score is associated with outcome after infant cardiac surgery: An analysis from the pediatric cardiac critical care consortium and virtual PICU system registries. Pediatric Critical Care Medicine, 2014, vol. 15, pp. 529–537. DOI: 10.1097/PCC.0000000000000153.

5. Donohue J.E., Yu S., Gall C., Rice T.B. Vasoactive-Inotropic Score (VIS) is Associated with Outcome After Infant Cardiac Surgery: An Analysis from the Pediatric Cardiac Critical Care Consortium (PC4) and Virtual PICU System Registries. Pediatric critical care medicine, 2015, vol. 15, pp. 529–537. DOI: 10.1097/PCC.0000000000000153.

6. Song J., Cho H., Park D.W. et al. Vasoactive-inotropic score as an early predictor of mortality in adult patients with sepsis. J Clin Med, 2021, vol. 10, no. 3, pp. 495.

7. Huang A.C.C., Lee T.Y.T., Ko M. et al. Fluid balance correlates with clinical course of multiple organ dysfunction syndrome and mortality in patients Конфликт интересов. Авторы заявляют об отсутствии у них конфликта интересов. Conflict of Interests. The authors state that they have no conflict of interests. with septic shock. PLoS One, 2019, vol. 14, no. 12, pp. e0225423. DOI: 10.1371/JOURNAL.PONE.0225423.

8. Chousterman B.G., Swirski F.K., Weber G.F. Cytokine storm and sepsis disease pathogenesis. Semin Immunopathol, 2017, vol. 39, pp. 517–528. DOI: 10.1007/s00281-017-0639-8.

9. Velissaris D., Pantzaris N.-D., Bountouris P., Gogos C. Correlation between neutrophil-to-lymphocyte ratio and severity scores in septic patients upon hospital admission. A series of 50 patients. Romanian Journal of Internal Medicine, 2018, vol. 56, pp. 153–157. DOI: 10.2478/rjim-2018-0005.

10. Chan A.S., Rout A. Use of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in COVID-19. J Clin Med Res, 2020, vol. 12, pp. 448–453. DOI: 10.14740/jocmr4240.

11. Jiang J., Liu R., Yu X. et al. The neutrophil-lymphocyte count ratio as a diagnostic marker for bacteraemia: A systematic review and meta-analysis. Am J Emerg Med, 2019, vol. 37, pp. 1482–1489. DOI: 10.1016/j.ajem.2018.10.057.

12. Li X., Liu C., Mao Z. et al. Predictive values of neutrophil-to-lymphocyte ratio on disease severity and mortality in COVID-19 patients: a systematic review and meta-analysis. Crit Care, 2020, vol. 24, no. 1, pp. 647. DOI: 10.1186/s13054-020-03374-8.

13. Buonacera A., Stancanelli B., Colaci M., Malatino L. Neutrophil to lymphocyte ratio: an emerging marker of the relationships between the immune system and diseases. International Journal of Molecular Sciences, 2022, vol. 23, no. 7, pp. 3636. DOI: 10.3390/ijms23073636.

14. Drifte G., Dunn-Siegrist I., Tissières P., Pugin J. Innate immune functions of immature neutrophils in patients with sepsis and severe systemic inflammatory response Syndrome*. Crit Care Med, 2013, vol. 41, pp. 820–832. DOI: 10.1097/CCM.0b013e318274647d.

15. Veenith T., Martin H., Le Breuilly M. et al. High generation of reactive oxygen species from neutrophils in patients with severe COVID-19. Sci Rep, 2022, vol. 12, no. 1, pp. 10484. DOI: 10.1038/s41598-022-13825-7.

16. Laforge M., Elbim C., Frère C. et al. Tissue damage from neutrophil-induced oxidative stress in COVID-19. Nature Reviews Immunology. Nature Research, 2020, vol. 20, no. 9, pp. 515–516. DOI: 10.1038/s41577-020-0407-1.

17. Song J., Cho H., Won Park D. et al. Clinical medicine vasoactive-inotropic score as an early predictor of mortality in adult patients with sepsis. J Clin Med, 2021, vol. 10, pp. 495. DOI: 10.3390/jcm100.

18. Huang Z., Fu Z., Huang W., Huang K. Prognostic value of neutrophil-to-lymphocyte ratio in sepsis: A meta-analysis. Am J Emerg Med, 2020, vol. 38, pp. 641–647. DOI: 10.1016/j.ajem.2019.10.023.

19. Spoto S., Lupoi D.M., Valeriani E. et al. Diagnostic accuracy and prognostic value of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in septic patients outside the intensive care unit. Medicina (B Aires), 2021, vol. 57, pp. 811. DOI: 10.3390/medicina57080811.

20. Bangash M.N., Kong M., Pearse R.M. Use of inotropes and vasopressor agents in critically ill patients. Br J Pharmacol, 2012, vol. 165, pp. 2015–2033. DOI: 10.1111/j.1476-5381.2011.01588.x.

21. Kallekkattu D., Rameshkumar R., Chidambaram M. et al. Threshold of inotropic score and vasoactive–inotropic score for predicting mortality in pediatric septic shock. Indian J Pediatr, 2022, vol. 89, pp. 432–437. DOI: 10.1007/s12098-021-03846-x.

22. Bime C., Zhou T., Wang T. et al. Reactive oxygen species–associated molecular signature predicts survival in patients with sepsis. Pulm Circ, 2016, vol. 6, pp. 196–201. DOI: 10.1086/685547.

23. Belletti A., Lerose C.C., Zangrillo A., Landoni G. Vasoactive-inotropic score: evolution, clinical utility, and pitfalls. J Cardiothorac Vasc Anesth. 2021, vol. 35, pp. 3067–3077. DOI: 10.1053/j.jvca.2020.09.117.

24. Macdonald S. Fluid Resuscitation in patients presenting with sepsis: current insights. Open Access Emerg Med. 2022, vol. 14, pp. 633. DOI: 10.2147/OAEM. S363520.

25. Monnet X., Marik P.E., Teboul J.L. Prediction of fluid responsiveness: an update. Ann Intensive Care, 2016, vol. 6, pp. 111. DOI: 10.1186/S13613-016-0216-7.

26. Hyun D.G., Ahn J.H., Huh J.W. et al. Impact of a cumulative positive fluid balance during the first three ICU days in patients with sepsis, pp. a propensity score-matched cohort study. Ann Intensive Care, 2023, vol. 13, pp. 1–9. DOI: 10.1186/S13613-023-01178-X/FIGURES/4.

27. Crimi E., Sica V., Williams-Ignarro S. et al. The role of oxidative stress in adult critical care. Free Radic Biol Med, 2006, vol. 40, pp. 398–406. DOI: 10.1016/J. FREERADBIOMED.2005.10.054.

28. Ibarz M., Boumendil A., Haas L.E.M. et al. Sepsis at ICU admission does not decrease 30-day survival in very old patients: a post-hoc analysis of the VIP1 multinational cohort study. Ann Intensive Care, 2020, vol. 10, pp. 1–12. DOI: 10.1186/S13613-020-00672-W/TABLES/3.

29. Shim H., Jang J.Y., Lee S.H., Lee J.G. Correlation of the oxygen radical activity and antioxidants and severity in critically ill surgical patients – study protocol. World Journal of Emergency Surgery, 2013, vol. 8, pp. 1–4. DOI: 10.1186/1749-7922-8-18/TABLES/1.

30. Payen D., de Pont A.C., Sakr Y. et al. A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit Care, 2008, vol. 12, no. 3, pp. R74. DOI: 10.1186/CC6916.

31. Marik P.E., Byrne L., van Haren F. Fluid resuscitation in sepsis: The great 30 mL per kg hoax. Journal of Thoracic Disease, 2020, vol. 12, Suppl 1, pp. S37– S47. DOI: 10.21037/jtd.2019.12.84.

32. Zhang L., Xu F., Li S. et al. Influence of fluid balance on the prognosis of patients with sepsis. BMC Anesthesiol, 2021, vol. 21, no. 1, pp. 269. DOI: 10.1186/s12871-021-01489-1.

33. Hoste E.A., Maitland K., Brudney C.S. et al. Four phases of intravenous fluid therapy, pp. a conceptual model. Br J Anaesth, 2014, vol. 113, pp. 740–747. DOI: 10.1093/BJA/AEU300.

34. Biswal S., Remick D.G. Sepsis: redox mechanisms and therapeutic opportunities. Antioxid Redox Signal, 2007, vol. 9, pp. 1959. DOI: 10.1089/ARS.2007.1808.

35. Fataya E., Fadrian, Noer M., Elvira D. et al. Characteristics of adult sepsis patients admitted to department of internal medicine, Dr. M. Djamil General Hospital, Padang, Indonesia. Bioscientia Medicina: Journal of Biomedicine and Translational Research, 2023, vol. 7, pp. 3191–3198. DOI: 10.37275/BSM.V7I3.791.

36. Abu-Humaidan A.H.A., Ahmad F.M., Al-Binni M.A. et al. Characteristics of adult sepsis patients in the intensive care units in a tertiary hospital in Jordan: An observational study. Crit Care Res Pract, 2021, vol. 2021, pp. 2741271. DOI: 10.1155/2021/2741271.

37. Abe T., Ogura H., Shiraishi A. et al. Characteristics, management, and in-hospital mortality among patients with severe sepsis in intensive care units in Japan: The FORECAST study. Crit Care, 2018, vol. 22, pp. 1–12. DOI: 10.1186/S13054-018-2186-7/TABLES/7.