Clinical and economic assessment of the therapy of acute kidney injury in sepsis with continuous combined methods of renal replacement therapy

Objective: complex assessment of clinical and economic effectiveness as well as saving of the state budget assets within the therapy of patients with sepsis/septic shock based on different technologies of blood purification.

Methods. Evaluation of direct and indirect costs of the eight blood purifcation methods. The target population includes adult patients 18+ with septic acute kidney injury. The study was conducted in compliance with acting Standards on Clinical Economic Studies used in the Russian Federation.

The study methods included evaluation of existing randomized clinical studies and trials with data from network meta-analyses and systematic reviews of the target technologies. The direct medical and indirect non-medical costs were calculated and analyzed in respect of cost-effectiveness  and budget impact analyses.

Results. Direct and indirect costs were calculated for the sorption devices oXiris (Baxter International Inc.), Toraymyxin (Toray Medical Co.), Alteco LPS Adsorber (Alteco Medical AB), Toxipak (POKARD NPF), Desepta.LPS (BIOTECH M NPP), CytoSorb (CytoSorbents Inc.), HA330 (Jafron Biomedical Co.), Desepta (BIOTECH M NPP) for two time-horizons: 1-year period and 5-years period with discounting. For both periods, the use of oXiris hemoflter results in the least economic burden for the state budget.

Conclusion. The use of blood purifcation in septic patients therapy is associated with considerable direct and indirect fnancial expenses, the amount of which and consequential budget saving depend on the technology of blood purifcation applied. The actual tariff compensation policy evidently demands revising.

1. Аndrusev А.M., Tomilina N.А., Peregudova N.G. et al. Zamestitelnaya terapiya terminalnoy khronicheskoy pochechnoy nedostatochnosti v Rossiyskoy Federatsii 2014-2018 gg. Otchet po dannym Obscherossiyskogo Registra zamestitelnoy pochechnou terapii Rossiyskogo dializnogo obschestva. [Replacement therapy for terminal chronic kindey disease in the Russian Federation 2014-2018. Report based on data of the All-Russian Register of Substitutive Renal Therapy of the Russian Dialysis Society]. Available: https://clck.ru/Vzmjr (Accessed: 30.06.2021).

2. Kim T.G., Magomedov M.А., Protsenko D.N. et al. The current state of renal replacement therapy in the treatment of sepsis. Messenger of Anesthesiology and Resuscitation, 2021, no. 4 (18). (In Russ.) doi:10.21292/2078-5658-2021-18-4-80-89.

3. Metodicheskie rekomendatsii po provedeniyu sravnitelnoy kliniko-ekonomicheskoy otsenki lekarstvennogo preparata (novaya redaktsiya). [Guidelines for comparative clinical and economic evaluation of drugs (new revision)]. Approved by Edict No.242-od as of 29.12.2018 by FGBU TsEKKMP of the Russian Ministry of Health. (Epub.), Available: https://rosmedex.ru/wp-content/uploads/2019/06/MR-KE%60I_novaya-redaktsiya_2018-g.pdf (Accessed 15.05.2021).

4. Metodicheskie rekomendatsii po sposobam oplaty meditsinskoy pomoschi za schet sredstv obyazatelnogo meditsinskogo strakhovaniya na 2021 god.[Guidelines on the methods of payment for medical help from mandatory medical insurance fund for 2021]. Edited by the Russian Ministry of Health, Russian Federal Mandatory Medical Insurance Fund, Moscow, 2021, (Epub.), Available: https://rosmedex.ru/wp-content/uploads/2021/04/metodicheskie-rekomendaczii.pdf (Accessed: 22.05.2021).

5. Optimizatsiya metodov ekstrakorporalnoy gemokorrektsii u bolnykh s tyazhelym sepsisom. Metodicheskie rekomendatsii No. 26. Optimizatsiya. [Optimization of extracorporeal hemocorrection methods in patients with severe sepsis. Guidelines No 26. Optimization]. Moscow, 2017, (Epub.), Available: http://mosgorzdrav.ru/ru-RU/science/default/download/364.html (Accessed: 29.05.2021).

6. Polushin Y.S., Sokolov D.V., Belousov D.Y. et al. Pharmacoeconomic assessment of intermittent and continuous renal replacement therapy. Messenger of Anesthesiology and Resuscitation, 2017, no. 6 (14), pp. 6-20. (In Russ.) doi: 10.21292/2078-5658-2017-14-6-6-2.

7. 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.

8. Unarokov Z.M., Borisov А.S., Sokolnikova T.А. et al. Prolonged intermittent dialysis as an alternative to continuous renal replacement therapy in critically ill patients: a systematic review and meta-analysis. Patologiya Krovoobrascheniya i Kardiokhirurgiya, 2016, no. 1 (20), pp. 25-34. (In Russ.) doi: 10.21688/1681-3472-2016-1-25-34.

9. Yagudina R.I., Аbdrashitova G.T., Serpik V.G. 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, no. 3 (3), pp. 103-110. (In Russ.)

10. Yagudina R.I., Аbdrashitova G.T., Serpik V.G. et al. Economic burden of chronic renal disease in the Russian Federation. Farmakoekonomika: Teoriya i Praktika, 2014, no. 4 (2), pp. 34-39. (In Russ.)

11. Case J., Khan S., Khalid R. et al. Epidemiology of acute kidney injury in the intensive care unit. Crit. Care Res. Pract., 2013, (2013). doi: 10.1155/2013/479730.

12. Eloot S., Biesen W. van, Dhondt A. et al. Impact of hemodialysis duration on the removal of uremic retention solutes. Kidney International, 2008, no. 6 (73). doi: 10.1038/sj.ki.5002750.

13. Ethgen O., Schneider A.G., Bagshaw S.M. et al. Economics of dialysis dependence following renal replacement therapy for critically ill acute kidney injury patients. Nephrol. Dial. Transplantat., 2015, no. 1 (30). doi: 10.1093/ndt/gfu314.

14. Farese S., Jakob S. M., Kalicki R. et al. Treatment of acute renal failure in the intensive care unit: lower costs by intermittent dialysis than continuous venovenous hemodiafiltration // Artific. Organs. ‒ 2009. ‒ № 8 (33). doi: 10.1111/j.1525-1594.2009.00794.x.

15. Gemmell L., Docking R., Black E. Renal replacement therapy in critical care // BJA Education. ‒ 2017. ‒ № 3 (17). doi: 10.1093/bjaed/mkw070.

16. Hawchar F., László I., Öveges N. et al. Extracorporeal cytokine adsorption in septic shock: A proof of concept randomized, controlled pilot study // J. Crit. Care. ‒ 2019. ‒ № 49. doi: 10.1016/j.jcrc.2018.11.003.

17. Iba T., Fowler L. Is polymyxin B-immobilized fiber column ineffective for septic shock? A discussion on the press release for EUPHRATES trial // J. Intens. Care. ‒ 2017. ‒ № 1 (5). doi: 10.1186/s40560-017-0236-x.

18. Incidence of severe sepsis and septic shock in German intensive care units: the prospective, multicentre INSEP study // Intens. Care Med. ‒ 2016. ‒ № 12 (42). doi: 10.1007/s00134-016-4504-3.

19. Kawanishi H. Terminology and classification of blood purification in critical care in Japan Basel: KARGER, 2010. doi: 10.1159/000314846.

20. 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. ‒ № 1 (6). doi: 10.15441/ceem.18.007.

21. 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. ‒ № 12 (44). doi: 10.1007/s00134-018-5463-7.

22. Malard B., Lambert C., Kellum J. A. In vitro comparison of the adsorption of inflammatory mediators by blood purification devices // Intens. Care Med. Experim. ‒ 2018. ‒ № 1 (6). doi: 10.1186/s40635-018-0177-2.

23. Mayr F. B. Infection rate and acute organ dysfunction risk as explanations for racial differences in severe sepsis // JAMA. ‒ 2010. ‒ № 24 (303). doi: 10.1001/jama.2010.851.

24. Monard C., Rimmelé T., Ronco C. Extracorporeal blood purification therapies for sepsis // Blood Purificat. ‒ 2019. ‒ Suppl. 3 (47). doi: 10.1159/000499520.

25. 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. ‒ № 12 (46). doi: 10.1097/CCM.0000000000003342.

26. Ronco C., Ricci Z., Backer D. et al. Renal replacement therapy in acute kidney injury: controversy and consensus // Crit. Care. ‒ 2015. ‒ № 1 (19). doi:10.1097/CCM.0000000000003342.

27. 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. ‒ № 10219 (395). doi: 10.1016/S0140-6736(19)32989-7.

28. 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. ‒ Doc 01 (13). doi: 10.3205/hta000127.

29. 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 Purificat. ‒ 2020. doi: 10.3205/hta000127.

30. Sun Z., Ye H., Shen X. et al. Continuous venovenous hemofiltration versus extended daily hemofiltration in patients with septic acute kidney injury: a retrospective cohort study // Crit. Care. ‒ 2014. ‒ № 2 (18). doi: 10.3205/hta000127.

31. Thomas M., Moriyama K., Ledebo I. AN69: Evolution of the world’s first high permeability membrane 2011. doi: 10.3205/hta000127.

32. 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 Quality (US), 2016. [Электронный ресурс]. URL: https://www.ncbi.nlm.nih.gov/books/NBK368492/ (дата обращения:14.06.2021).

33. Turani F., Barchetta R., Falco M. et al. Continuous renal replacement therapy with the adsorbing filter Oxiris in septic patients: a case series // Blood Purification. ‒ 2019. ‒ Suppl. 3 (47). doi: 10.1159/000499589.

34. 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. ‒ № 4 (42). doi:10.1159/000499589.

35. Yaroustovsky M., Abramyan M., Popok Z. et al. Preliminary report regarding the use of selective sorbents in complex cardiac surgery patients with extensive sepsis and prolonged intensive care stay // Blood Purification. ‒ 2009. ‒ № 3 (28). doi: 10.1159/000231988.

36. Yumoto M., Nishida O., Moriyama K. et al. In vitro evaluation of high mobility group box 1 protein removal with various membranes for continuous hemofiltration // Therap. Apher. Dialys. ‒ 2011. ‒ № 4 (15). doi: 10.1111/j.1744-9987.2011.00971.x.

37. Zhang L., Yang J., Eastwood G. M. et al. Extended daily dialysis versus continuous renal replacement therapy for acute kidney injury: a meta-analysis // Am. J. Kidney Dis. ‒ 2015. ‒ № 2 (66). doi: 10.1053/j.ajkd.2015.02.328.

38. Zhou F., Peng Z., Murugan R. et al. Blood purification and mortality in sepsis // Crit. Care Med. ‒ 2013. ‒ № 9 (41). doi: 10.1097/CCM.0b013e31828cf412.