Clinical and Economic Evaluation of the Blood Purification with Selective Sorption Techniques in ICU Patients

The objective was to analyze the clinical and economic feasibility of using selective methods  of lipopolysaccharide (LPS) sorption  for sepsis treatment.

Materials and methods.  A clinical and economic model was used to assess the feasibility of using some technologies of selective lipopolysaccharide sorption. The model was developed in accordance with the current industry standard «Clinical and Economic Research» used in Russia. The target  population was patients of 18 years old and older with sepsis. The methodology involved the evaluation of available randomized clinical trials, as well as studies involving data from network meta-analyses and systematic  reviews of the use of the studied  technologies. The calculation of direct  medical and indirect non-medical  costs was made with an analysis of the impact on the budget  during  the first year and on the time horizon for five years.

Results. The value of direct  and indirect costs was determined when using sorption  devices based on Efferon LPS, Toraymyxin,  Alteco LPS Adsorber,  Toxipak  columns. It was shown that  among the therapeutic alternatives, the use of the Efferon LPS column had the least burden on the budget.

Conclusion. The  use of selective  lipopolysaccharide sorption  technologies in the  intensive  care program  for sepsis patients, although accompanied  by an increase  in direct  and indirect financial costs, leads to budget  savings in the medium  term. Improving  the mechanism  for compensating the costs of using this technology is a promising way to improve the outcomes of sepsis treatment.

1. Guidelines for comparative clinical and economic evaluation of drugs (new revision). Approved by Edict No.242-od as of 29.12.2018 by Center for Healthcare Quality Assessment and Control of the Ministry of Health of the Russian Federation provides expertise, information and methodological support in implementing healthcare policy. (In Russ.) (Epub.), Available: https://clck.ru/GqdJz (Accessed 28.07.2022) (In Russ.).

2. Paternoster D., Nagi A. Immunomodulation, immunostimulation and extracorporal blood purification for sepsis: prospectives for the technologies use in cardio surgery. Messenger of Anesthesiology and Resuscitation, 2019, vol. 16, no. 2, pp. 96-106. (In Russ.). Doi:10.21292/2078-5658-2019-16-2-96-106.

3. Polushin Yu. S., Dreval R. O., Zabotina A. N. Clinical and economic assessment of the therapy of acute kidney injury in sepsis with continuous combined methods of renal replacement therapy. Messenger of Anesthesiology and Resuscitation, 2021, vol. 18, no 5, pp. 7-20. (In Russ.) Doi: 10.21292/2078-5658-2021-18-5-7-20.

4. Polushin Yu. S., Sokolov D. V., Belousov D. Yu., Cheberda A. E. Pharmaeco-nomic assessment of intermittent and continuous renal replacement therapy. Messenger of Anesthesiology and Resuscitation, 2017, vol. 14, no. 6, pp. 6-20. (In Russ.) Doi: 10.21292/2078-5658-2017-14-6-6-20.

5. Rubtsov M. S., Shukevich D. L. Modern extracorporeal methods for critical conditions caused by systemic inflammatory response (review). Anesteziologiya i Reanimatologiya, 2019, no. 4, pp. 20-30. (In Russ.) Doi:10.17116/anaesthesiology201904120.

6. Sepsis: classification, clinical diagnostic concept, and treatment. / Eds. by B. R. Gelfand. 4th ed., revised. Moscow, Medical information agency, 2017, 408 p. (In Russ.). ISBN: 978-5-8948-1988-4.

7. Yagudina R. I., Abdrashitova G. T., Serpik V. G. Economic burden of chronic renal disease in the Russian Federation. Farmakoekonomika: Teoriya i Praktika, 2014, vol. 2, no. 4, pp. 34-39. (In Russ.). Doi:10.30809/phe.3.2015.2.

8. Yagudina R. I., Abdrashitova G. T., Serpik V. G. et al. Pharmaco-economic analysis of medical care for patients with chronic renal disease in need of renal replacement therapy through peritoneal dialysis and hemodialysis in the Russian health system. Farmakoekonomika: Teoriya i Praktika, 2015, vol. 3, no. 3, pp. 103-110. (In Russ.). Doi:10.30809/phe.4.2014.5.

9. Abdollahi M., Chelkeba L., Ahmadi A. et al. Early goal-directed therapy reduces mortality in adult patients with severe sepsis and septic shock: Systematic review and meta-analysis. Indian J Crit Care Med, 2015, vol. 19, no. 7, pp. 401-11. Doi: 10.4103/0972-5229.160281.

10. Bagshaw S. M., Uchino S., Bellomo R. et al. Beginning and ending supportive therapy for the kidney (BEST Kidney) investigators. Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol, 2007, vol. 2, no. 3, pp. 431-9. Doi: 10.2215/CJN.03681106.

11. Beltran-Garda J., Osca-Verdegal R., Pallardo F V. et al. Sepsis and coronavirus disease 2019: common features and anti-inflammatory therapeutic approaches. Crit Care Med, 2020, vol. 48, no. 12, pp. 1841-1844. Doi: 10.1097/CCM.0000000000004625.

12. Bottiroli M., Monti G., Pinciroli R. et al. Prevalence and clinical significance of early high endotoxin activity in septic shock: an observational study. Journal of Critical Care, 2017, no. 41, pp. 124-129. Doi:10.1016/j.jcrc.2017.04.030

13. Case J., Khan S., Khalid R. et al. Epidemiology of acute kidney injury in the intensive care unit. Crit Care Res Pract, 2013, no. 2013, p. 479730. Doi:: 10.1155/2013/479730.

14. Dellinger R. P., Bagshaw S. M., Antonelli M. et al. Effect of targeted polymyxin B hemoperfusion on 28-day mortality in patients with septic shock and elevated endotoxin level: the EUPHRATES randomized clinical trial. JAMA, 2018, vol. 320, no. 14, pp. 1455-1463. Doi:10.1001/jama.2018.14618.

15. Dupuis C., Bouadma L., Ruckly S. et al. Sepsis and septic shock in France: incidences, outcomes and costs of care. Ann Intensive Care, 2020, vol. 10, no. 1, pp. 145. Doi: 10.1186/s13613-020-00760-x.

16. Evans L., Rhodes A., Alhazzani W. et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med, 2021, vol. 49, no. 11, pp. e1063-e1143. Doi:10.1097/CCM.0000000000005337.

17. Gemmell L., Docking R., Black E. Renal replacement therapy in critical care. BJA Education, 2017, no. 17, pp. 88-93. Doi:: 10.1093/bjaed/mkw070.

18. Gotts J. E., Matthay M. A. Sepsis: pathophysiology and clinical management. BMJ, 2016, no. 353, pp. i1585. Doi:10.1136/bmj.i1585.

19. Hoste E. A., Bagshaw S. M., Bellomo R. et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med, 2015, vol. 41, no. 8, pp. 1411-1423. Doi: 10.1007/s00134-015-3934-7.

20. Incidence of severe sepsis and septic shock in German intensive care units: the prospective, multicentre INSEP study. Intensive Care Med, 2016, vol. 42, no. 12, pp. 1980-1989. Doi: 10.1007/s00134-016-4504-3.

21. Kim J., Kim K., Lee H. et al. Epidemiology of sepsis in Korea: a population-based study of incidence, mortality, cost and risk factors for death in sepsis. Clin. Experim. Emerg. Med., 2019, vol. 6, no. 1, pp. 49-63. Doi: 10.15441/ceem.18.007.

22. Klein D. J., Foster D., Walker P. M. et al. Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia: a post hoc analysis of the EUPHRATES trial. Intens. Care Med., 2018, vol. 44, no. 12, pp. 2205-2212. Doi: 10.1007/s00134-018-5463-7.

23. Lai T. S., Wang C. Y., Pan S. C. et al. Risk of developing severe sepsis after acute kidney injury: a population-based cohort study. Crit Care, 2013, vol. 17, no. 5, pp. R231. Doi: 10.1186/cc13054.

24. Lipcsey M., Tenhunen J., Pischke S. E. et al. Endotoxin removal in septic shock with the alteco LPS adsorber was safe but showed no benefit compared to placebo in the double-blind randomized controlled trial-the asset study. Shock, 2020, vol. 54, no. 2, pp. 224-231. Doi: 10.1097/SHK.0000000000001503.

25. Lipcsey M., Tenhunen J., Sjolin J. et al. Abdominal Septic Shock - Endotoxin adsorption treatment (ASSET) - endotoxin removal in abdominal and urogenital septic shock with the Alteco® LPS Adsorber: study protocol for a double-blinded, randomized placebo-controlled trial. Trials, 2016, vol. 17, no. 1, pp. 587. Doi: 10.1186/s13063-016-1723-4.

26. Marik P. E. Don't miss the diagnosis of sepsis! Crit Care, 2014, vol. 18, no. , pp. 1-3. Doi: 10.1186/s13054-014-0529-6.

27. Mat-Nor M. B., Ralib A., Abdulah N. Z. et al. The diagnostic ability of procalcitonin and interleukin-6 to differentiate infectious from noninfectious systemic inflammatory response syndrome and to predict mortality. Journal of critical care, 2016, no. 33, pp. 245-251. Doi: 10.1016/j.jcrc.2016.01.002.

28. Mayr F. B. Infection rate and acute organ dysfunction risk as explanations for racial differences in severe sepsis. JAMA, 2010, vol. 303, no. 24. Doi: 10.1001/jama.2010.851.

29. Monard C., Rimmele T., Ronco C. Extracorporeal blood purification therapies for sepsis. Blood Purif, 2019; no. 47, suppl. 3, pp. 1-14. Doi: 10.1159/000499520.

30. Paoli C. J., Reynolds M. A., Sinha M. et al. Epidemiology and costs of sepsis in the united states - an analysis based on timing of diagnosis and severity level. Crit. Care Med., 2018, vol. 46, no. 12. Doi: 10.1097/CCM.0000000000003342.

31. Rudd K. E., Johnson S. C., Agesa K. M. et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet, 2020, vol. 395, no. 10219. Doi: 10.1016/S0140-6736(19)32989-7.

32. Schoenfelder T., Chen X., Bleb H. H. Effects of continuous and intermittent renal replacement therapies among adult patients with acute kidney injury. GMS Health Technology Assessment, 2017, no. 13, doc 01. Doi: 10.3205/hta000127.

33. Snow T. A. C., Littlewood S., Corredor C. et al. Effect of extracorporeal blood purification on mortality in sepsis: a meta-analysis and trial sequential analysis. Blood Purif., 2021, vol. 50, no. 4-5, pp. 462-472.

34. Tiru B., DiNino E. K., Orenstein A. et al. The economic and humanistic burden of severe sepsis. Pharmacoeconomics, 2015, vol. 33, no. 9, pp. 925-937. Doi: 10.1007/s40273-015-0282-y.

35. Torio C. M., Moore B. J. National inpatient hospital costs. The most expensive conditions by payer, 2013. Statistical Brief #204 Rockville (MD). Agency for healthcare research and ouality (US), 2016. (Epub.), Available: https://www.ncbi.nlm.nih.gov/books/NBK368492/ (Accessed: 09.02. 2023).

36. Wald R., Shariff S. Z., Adhikari N. K. J. et al. The association between renal replacement therapy modality and long-term outcomes among critically ill adults with acute kidney injury. Crit. Care Med., 2014, vol. 4, no. 42, pp. 868-77. Doi: 10.1159/000499589.

37. Ye Z., Wang Y., Ge L. et al. Comparing renal replacement therapy modalities in critically ill patients with acute kidney injury: a systematic review and network meta-analysis. Crit Care Explor., 2021; vol. 3, no. 5, pp. e0399. Doi: 10.1097/CCE.0000000000000399.

38. Zhou F., Peng Z., Murugan R. et al. Blood purification and mortality in sepsis. Crit. Care Med., 2013, vol. 41, no. 9. Doi: 10.1097/CCM.0b013e31828cf412.