The experience of using succinate-containing crystalloid solution in the correction of COVID-19-associated endotheliopathy

Abstract

BACKGROUND: Early experience with succinate-containing agents has demonstrated their effectiveness in controlling COVID-19-related systemic disease and coagulopathy. The work is aimed at studying the possibilities of infusion correction of COVID-19-associated endotheliopathy.

AIM: To evaluate the effect of using meglumine sodium succinate 1.5% solution on the severity of COVID-19-associated endotheliopathy in patients with severe coronavirus infection.

MATERIALS AND METHODS: Clinical and laboratory parameters of 53 patients in the intensive care unit with COVID-19 complicated by community-acquired bilateral polysegmental pneumonia were analyzed. The intensive care package for 27 patients (study group) included a daily infusion of a 1.5% solution of meglumine sodium succinate (Reamberin) in a daily dose of up to 10 ml/kg for a course of at least 11 days or during the entire stay in the department. The control group, which included 26 patients, received a similar volume of Ringer’s solution. At all stages of the study, the level of endotheliocytosis, homocysteine, fibrinogen, activated partial thromboplastin time, platelet count, and antithrombin III was determined.

RESULTS: Assessment of the degree of endotheliopathy in the meglumine succinate group showed a significant decrease in the initially elevated levels of endothelemia and homocysteinemia at all stages of the study. The pattern of changes in the study group highly correlated (r values were in the range 0.90–0.96) with the dynamics of fibrinogenemia, platelet levels, and antithrombin III.

CONCLUSIONS: The use of a succinate-containing infusion solution in patients with a new coronavirus infection promotes a more rapid and sustainable correction of COVID-19-associated endotheliopathy, which, in turn, is manifested by a decrease in the levels of endotheliocytosis, secondary markers of endotheliopathy, a platelet-protective effect and a decrease in heparin resistance.

Keywords

COVID-19 / endothelial dysfunction / endotheliopathy / succinate / meglumine sodium succinate

References

[1] Escher R, Breakey N, Lämmle B. Severe COVID-19 infection associated with endothelial activation. Thromb Res. 2020;190:62. doi: 10.1016/j.thromres.2020.04.014

[2] Escher R., Breakey N., Lämmle B. Severe COVID-19 infection associated with endothelial activation // Thromb Res. 2020. Vol. 190. P. 62. doi: 10.1016/j.thromres.2020.04.014

[3] Moreno-Castaño A, Fernández S, Palomo M, et al. Circulating biomarkers of COVID-19-triggered endotheliopathy: From conjecture to certainty. Blood. 2020;136:31–32. doi: 10.1182/blood-2020-142311

[4] Moreno-Castaño A., Fernández S., Palomo M., et al. Circulating biomarkers of COVID-19-triggered endotheliopathy: From conjecture to certainty // Blood. 2020. Vol. 136. P. 31–32. doi: 10.1182/blood-2020-142311

[5] Shabrov AV, Apresyan AG, Dobkes AL, et al. Current methods of endothelial dysfunction assessment and their possible use in the practical medicine. Rational Pharmacotherapy in Cardiology. 2016;12(6):733–742. EDN: XSALQB doi: 10.20996/1819-6446-2016-12-6-733-742

[6] Шабров А.В., Апресян А.Г., Добкес А.Л., и др. Современные методы оценки эндотелиальной дисфункции и возможности их применения в практической медицине // Рациональная фармакотерапия в кардиологии. 2016. Т. 12, № 6. С. 733–742. EDN: XSALQB doi: 10.20996/1819-6446-2016-12-6-733-742

[7] Gainetdinov RR, Kurochkin SV. Lung lesions caused by COVID-19 in comparison with bacterial pneumonia and influenza pneumonia: Pathomorphological features. Kazan Medical Journal. 2021;102(5):703–715. EDN: COOORW doi: 10.17816/KMJ2021-703

[8] Гайнетдинов Р.Р., Курочкин С.В. Поражение легких при COVID-19 в сравнении с бактериальной пневмонией и пневмонией при гриппе: патоморфологические особенности // Казанский медицинский журнал. 2021. Т. 102, № 5. С. 703–715. EDN: COOORW doi: 10.17816/KMJ2021-703

[9] Camporota L, Cronin JN, Busana M, et al. Pathophysiology of coronavirus-19 disease acute lung injury. Curr Opin Crit Care. 2022;28(1):9–16. doi: 10.1097/MCC.0000000000000911

[10] Camporota L., Cronin J.N., Busana M., et al. Pathophysiology of coronavirus-19 disease acute lung injury // Curr Opin Crit Care. 2022. Vol. 28, N 1. P. 9–16. doi: 10.1097/MCC.0000000000000911

[11] Gattinoni L, Chiumello D, Rossi S. COVID-19 pneumonia: ARDS or not? Crit Care. 2020;24(1):154. doi: 10.1186/s13054-020-02880-z

[12] Gattinoni L., Chiumello D., Rossi S. COVID-19 pneumonia: ARDS or not? // Crit Care. 2020. Vol. 24, N 1. P. 154. doi: 10.1186/s13054-020-02880-z

[13] Nardelli P, Landoni G. COVID-19-related thromboinflammatory status: MicroCLOTS and beyond. General Reanimatology. 2020;16(3):14–15. EDN: ZHCOHL doi: 10.15360/1813-9779-2020-3-0-2

[14] Нарделли П., Ландони Дж. COVID-19-ассоциированный тромбовоспалительный статус: гипотеза MicroCLOTS и ее перспективы // Общая реаниматология. 2020. Т. 16, № 3. С. 14–15. EDN: ZHCOHL doi: 10.15360/1813-9779-2020-3-0-2

[15] Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N Engl J Med. 2020;383(2):120–128. doi: 10.1056/NEJMoa2015432

[16] Ackermann M., Verleden S.E., Kuehnel M., et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19 // N Engl J Med. 2020. Vol. 383, N 2. P. 120–128. doi: 10.1056/NEJMoa2015432

[17] Cheng H, Wang Y, Wang G-Q. Organ-protective effect of angiotensin-converting enzyme 2 and its effect on the prognosis of COVID-19. J Med Virol. 2020;92(7):726–730. doi: 10.1002/jmv.25785

[18] Cheng H., Wang Y., Wang G.-Q. Organ-protective effect of angiotensin-converting enzyme 2 and its effect on the prognosis of COVID-19 // J Med Virol. 2020. Vol. 92, N 7. P. 726–730. doi: 10.1002/jmv.25785

[19] McGonagle D, Bridgewood C, Meaney JFM. A tricompartmental model of lung oxygenation disruption to explain pulmonary and systemic pathology in severe COVID-19. Lancet Respir Med. 2021;9(6):665–672. doi: 10.1016/S2213-2600(21)00213-7

[20] McGonagle D., Bridgewood C., Meaney J.F.M. A tricompartmental model of lung oxygenation disruption to explain pulmonary and systemic pathology in severe COVID-19. // Lancet Respir Med. 2021. Vol. 9, N 6. P. 665–672. doi: 10.1016/S2213-2600(21)00213-7

[21] Temporary guidelines Prevention, diagnosis and treatment of new coronavirus infection (COVID-19). Version 16 (02/18/2022). 249 p. [Internet]. Available from: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/060/193/original/%D0%92%D0%9C%D0%A0_COVID-19_V16.pdf. Accessed: 14 Nov 2022. (In Russ.)

[22] Временные методические рекомендации Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19). Версия 16 (18.02.2022). 249 с. [Электронный ресурс]. Режим доступа: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/060/193/original _COVID-19_V16.pdf. Дата обращения: 14.11.2022.

[23] González-Ruiz FJ. Pharmacological and non-pharmacological strategies in coronavirus disease 2019: a literature review. Ann Med Surg. 2022;77:103709. doi: 10.1016/j.amsu.2022.103709

[24] González-Ruiz F.J. Pharmacological and non-pharmacological strategies in coronavirus disease 2019: a literature review // Ann Med Surg. 2022. Vol. 77. P. 103709. doi: 10.1016/j.amsu.2022.103709

[25] Boffi A, Ravenel M, Lupieri E, et al. Physiological response to prone positioning in intubated adults with COVID-19 acute respiratory distress syndrome: A retrospective study. Respir Res. 2022;23(1):320. doi: 10.1186/s12931-022-02247-8

[26] Boffi A., Ravenel M., Lupieri E., et al. Physiological response to prone positioning in intubated adults with COVID-19 acute respiratory distress syndrome: A retrospective study // Respir Res. 2022. Vol. 23, N 1. P. 320. doi: 10.1186/s12931-022-02247-8

[27] Chary MA, Barbuto AF, Izadmehr S, Hayes BD. COVID-19: Therapeutics and their toxicities. J Med Toxicol. 2020;16(3):284–294. doi: 10.1007/s13181-020-00777-5

[28] Chary M.A., Barbuto A.F., Izadmehr S., Hayes B.D. COVID-19: Therapeutics and their toxicities // J Med Toxicol. 2020. Vol. 16, N 3. P. 284–294. doi: 10.1007/s13181-020-00777-5

[29] Martin C, Cortegiani A, Gregoretti C, et al. Choice of fluids in critically ill patients. BMC Anesthesiol. 2018;18(1):200. doi: 10.1186/s12871-018-0669-3

[30] Martin C., Cortegiani A., Gregoretti C., et al. Choice of fluids in critically ill patients // BMC Anesthesiol. 2018. Vol. 18, N 1. P. 200. doi: 10.1186/s12871-018-0669-3

[31] Simutis IS, Boyarinov GA, Yuriev MYu, et al. Meglumine sodium succinate to correct COVID-19-associated coagulopathy: The feasibility study. General Reanimatology. 2021;17(3):50–64. EDN: AJBRBY doi: 10.15360/1813-9779-2021-3-50-6

[32] Симутис И.С., Бояринов Г.А., Юрьев М.Ю., и др. Первый опыт применения меглюмина натрия сукцината в коррекции COVID-19-ассоциированной коагулопатии // Общая реаниматология. 2021. Т. 17, № 3. С. 50–64. EDN: AJBRBY doi: 10.15360/1813-9779-2021-3-50-6

[33] Feoktistova VS, Vavilkova TV, Sirotkina OV, et al. The new approach to evaluation of dysfunction of endothelium: Detection of number of circulating endothelium cell using flow cytometry technique. Clinical laboratory diagnosis. 2015;60(4):23–39. EDN: TSEQJN

[34] Феоктистова B.C., Вавилова T.B., Сироткина О.В., и др. Новый подход к оценке дисфункции эндотелия: определение количества циркулирующих эндотелиальных клеток методом проточной цитометрии // Клиническая лабораторная диагностика. 2015. Т. 60, № 4. С. 23–39. EDN: TSEQJN

[35] Guervilly C, Burtey S, Sabatier F, et al. Circulating endothelial cells as a marker of endothelial injury in severe COVID-19. J Infect Dis. 2020;222(11):1789–1793. doi: 10.1093/infdis/jiaa528

[36] Guervilly C., Burtey S., Sabatier F., et al. Circulating endothelial cells as a marker of endothelial injury in severe COVID-19 // J Infect Dis. 2020. Vol. 222, N 11. P. 1789–1793. doi: 10.1093/infdis/jiaa528

[37] Gendron N, Smadja DM. Circulating endothelial cells: A new biomarker of endothelial dysfunction in hematological diseases. Ann Biol Clin (Paris). 2016;74(4):395–404. doi: 10.1684/abc.2016.1160

[38] Gendron N., Smadja D.M. Circulating endothelial cells: A new biomarker of endothelial dysfunction in hematological diseases // Ann Biol Clin (Paris). 2016. Vol. 74, N 4. P. 395–404. doi: 10.1684/abc.2016.1160

[39] Peng M, Yan Q-H, Gao Y, et al. World correlation between circulating endothelial cell level and acute respiratory distress syndrome in postoperative patients. World J Clin Cases. 2021;9(32):9731–9740. doi: 10.12998/wjcc.v9.i32.9731

[40] Peng M., Yan Q.-H., Gao Y., et al. World correlation between circulating endothelial cell level and acute respiratory distress syndrome in postoperative patients // World J Clin Cases. 2021. Vol. 9, N 32. P. 9731–9740. doi: 10.12998/wjcc.v9.i32.9731

[41] Mancuso P, Gidaro A, Gregato G, et al. Circulating endothelial progenitors are increased in COVID-19 patients and correlate with SARS-CoV-2 RNA in severe cases. J Thromb Haemost. 2020;18(10):2744–2750. doi: 10.1111/jth.15044

[42] Mancuso P., Gidaro A., Gregato G., et al. Circulating endothelial progenitors are increased in COVID-19 patients and correlate with SARS-CoV-2 RNA in severe cases // J Thromb Haemost. 2020. Vol. 18, N 10. P. 2744–2750. doi: 10.1111/jth.15044

[43] Vokhmianina NV, Gaikovaya LB, Evteeva DA, Vlasova YuA. Homocysteine as a predictor of the severity of coronavirus infection: biochemical justification. Laboratory Service. 2022;11(1):43–50. EDN: UIZZRL doi: 10.17116/labs20221101143

[44] Вохмянина Н.В., Гайковая Л.Б., Евтеева Д.А., Власова Ю.А. Гомоцистеин как предиктор тяжести течения коронавирусной инфекции: биохимическое обоснование // Лабораторная служба. 2022. Т. 11, № 1. С. 43–50. EDN: UIZZRL doi: 10.17116/labs20221101143

[45] Ponti G, Ruini C, Tomasi A. Homocysteine as a potential predictor of cardiovascular risk in patients with COVID-19. Med Hypotheses. 2020;143:109859. doi: 10.1016/j.mehy.2020.109859

[46] Ponti G., Ruini C., Tomasi A. Homocysteine as a potential predictor of cardiovascular risk in patients with COVID-19 // Med Hypotheses. 2020. Vol. 143. P. 109859. doi: 10.1016/j.mehy.2020.109859

[47] Mallat J, Lemyze M, Meddour M, et al. Ratios of central venous-to-arterial carbon dioxide content or tension to arteriovenous oxygen content are better markers of global anaerobic metabolism than lactate in septic shock patients. Ann Intensive Care. 2016;6(1):10. doi: 10.1186/s13613-016-0110-3

[48] Mallat J., Lemyze M., Meddour M., et al. Ratios of central venous-to-arterial carbon dioxide content or tension to arteriovenous oxygen content are better markers of global anaerobic metabolism than lactate in septic shock patients // Ann Intensive Care. 2016. Vol. 6, N 1. P. 10. doi: 10.1186/s13613-016-0110-3

RIGHTS & PERMISSIONS

Eco-Vector