Meglumine Sodium Succinate in Diabetic Ketoacidosis

The most common agent used for infusion therapy in patients with diabetic ketoacidosis (DKA) is isotonic 0.9% sodium chloride solution. However, infusion of required volumes can result in development of iatrogenic complications — i. e., worsening of metabolic hyperchloremic acidosis in DKA patients with already altered acid-base balance. Balanced crystalloid solutions can be used as alternative to saline.
Objective. To evaluate the feasibility of using meglumine sodium succinate (MSS) balanced crystalloid solution in DKA.
Material and methods. We examined 2 groups of patients, 30 subjects each, with moderate and severe diabetic ketoacidosis admitted to anesthesiology and intensive care unit. Patients from both groups were administered with insulin and an infusion therapy was employed according to current clinical guidelines for the management of patients with complications of diabetes mellitus. In the comparison group, infusion therapy included 0.9% sodium chloride, 4% potassium chloride, and 5% dextrose. In the study group MSS intravenous drip infusions 10 ml/kg/daily were added to the infusion protocol. Volumes and infusion rates were comparable in both groups. The following indicators were evaluated: time to resolution and DKA resolution rates during thorough monitoring (first 48 hours of therapy), the time (in hours) before discontinuation of insulin infusion; the time to complete consciousness recovery (15 items on the Glasgow Coma scale); the duration (in hours) of stay in the intensive care unit (ICU), dynamics of blood electrolytes; parameters of acid-base balance; levels of glycemia and lactatemia.
Results. All patients improved and were transferred from ICU, the mortality rate was 0%. Infusion of MSS shortened the time to DKA resolution (30.0 h [24.0 h; 36.0 h] in the study group, vs 44.5 h [36.5 h; 51.5 h] in the comparison group (P=0.001)); DKA resolution rates during 48 hours from initiation of therapy achieved 90.0% (27) in the study group, vs 66.7% (20) in the comparison group (P=0.060)); duration of intravenous insulin infusion was 32.0 h [24.5 h; 40.0 h] in the study group vs 48.0 h [40.0 h; 55.5 h] in the comparison group (P=0.001)); duration of ICU stay was 41.0 h [30.0 h; 48.0 h] in the study group, vs 56.0 h [50.0 h; 66.3 h] in the comparison group (P=0.001).
Conclusion. Infusion of a balanced succinate-containing crystalloid solution improves the results of DKA treatment, as compared to traditional infusion of 0.9% sodium chloride.

1. Zabolotskikh I. B., Protsenko D. N. Intensive care: national guidelines. Vol. 2. 2nd ed., rev. and exp. M.: GEOTAR-Media; 2022: 1056. (in Russ.) DOI: 10.33029/9704-5018-5. ISBN 978-5-9704-6259-1.

2. Shestakova M.V., Vikulova O.K., Zheleznyakova A.V., Isakov M.A., Dedov I.I. Diabetes epidemiology in Russia: what has changed over the decade? Ter. Arkh/Terapevticheskiy Arkhiv. 2019; 91 (10): 4–13. (in Russ.). DOI: 10.26442/00403660.2019.10.000364

3. Jahangir A., Jahangir A., Siddiqui F.S., Niazi M.R.K., Yousaf F., Muhammad M., Sahra S. et al. Normal saline versus low chloride solutions in treatment of diabetic ketoacidosis: a systematic review of clinical trials. Cureus 14 (1): e21324. DOI: 10.7759/cureus.21324. PMID: 35186583

4. Roizen M. F., Fleisher L. A. Perioperative management of patients with concomitant diseases. In the book: «Anesthesia» by Ronald Miller (ed.). in 4 vols. St. Petersburg: Man/Chelovek; 2015 (2): 1139–1234. (in Russ.)

5. Standards of specialized diabetes care. Ed. by Dedov I.I., Shestakova M.V., Mayorov A.Yu. 10th ed. (revised). M.; 2021. (in Russ.). DOI: 10.14341/DM12802

6. Kovalenko A.L., Rizakhanov D.M., Yakovlev A.Yu., Simutis I.S., Parfenov S.A., Bobovnik S.V., Sorokin et al. Preliminary results of adding meglumine sodium succinate to the treatment of patients with moderate and severe acute pancreatitis. General Reanimatology/Obshchaya Reanimatologya. 2021; 17 (1): 46–56. (in Russ.). DOI: 10.15360/1813-9779-2021-1-0-1

7. Simutis I.S., Boyarinov G.A., Yuryev M.Yu., Petrovsky D.S., Kovalenko A.L., Sapozhnikov K.V. A new look at the correction of COVID-19-mediated pulmonary gas exchange disorders. Kazan Medical Journal/Kazanskiy Meditsinkiy Zhurnal. 2021; 102 (3): 362–372. (in Russ.). DOI: 10.17816/KMJ2021-362.

8. Handy J.M., Soni N. Physiological effects of hyperchloraemia and acidosis. Br J Anaesth. 2008; 101 (2): 141–150. DOI: 10.1093/bja/aen148. PMID: 18534973

9. Simutis I.S., Boyarinov G.A., Yuriev M.Yu., Petrovsky D.S., Kovalenko A.L., Sapozhnikov K.V. Meglumine sodium succinate to correct COVID-19-associated coagulopathy: the feasibility study. General Reanimatology/ Obshchaya Reanimatologya. 2021; 17 (3): 50–64. (in Russ). DOI: 10.15360/1813-9779-2021-3-50-64.

10. Federyakin D.V., Parfenov S.A., Veselov S.V., Kolgina N.Yu., Mayorov M.O., Sabitov T.F., Goncharuk A.V. et al. Hemodilution with meglumine sodium succinate during heart surgery in on-pump cardiac surgery. Cardiology and cardiovascular surgery/ Kardiologiya i SerdechnoSosudistaya Khirurgiya. 2020; 13 (2): 114–119. (in Russ.). DOI: 10.17116/kardio202013021114

11. Carrillo A.R., Elwood K., Werth C., Mitchell J., Sarangarm P. Balanced crystalloid versus normal saline as resuscitative fluid in diabetic ketoacidosis. Ann Pharmacother. 2022; 56 (9): 998–1006. DOI: 10.1177/10600280211063651. PMID: 34986659

12. Self W.H., Evans C.S., Jenkins C.A., Brown R.M., Casey J.D., Collins S.P., Coston T.D. et al. Clinical effects of balanced crystalloids vs saline in adults with diabetic ketoacidosis: a subgroup analysis of cluster randomized clinical trials. JAMA Netw Open. 2 020; 3 (11): e2024596. DOI: 10.1001/jamanetworkopen.2020.24596. PMID: 33196806.

13. Belkin A.A., Leiderman I.N., Kovalenko A.L., Ryazanova O.A., Parfenov S.A., Sapozhnikov K.V. Cytoflavin as a modulator of rehabilitation treatment of patients with ischemic stroke complicated by post-intensive care syndrome. S.S. Korsakov Journal of Neurology and Psychiatry/Zh. Nevrol.Psikhiatr. im. S.S. Korsakova. 2020; 120 (10): 27–32. (in Russ.). DOI: 10.17116/jnevro202012010127.

14. Glantz S.A. Medico-biological statistics. Translated from English M.: Praktika; 1998: 459.

15. Borovikov V.P. STATISTICA: the art of data analysis on a computer for professionals. St. Petersburg: Peter; 2001: 656. (in Russ.)

16. Eledrisi M.S., Elzouki A.-N. Management of diabetic ketoacidosis in adults: a narrative review. Saudi J Med Med Sci. 2020; 8 (3): 165–173. DOI: 10.4103/sjmms.sjmms_478_19. PMID: 32952507

17. Besen B.A.M.P., Boer W., Honore P.M. Fluid management in diabetic ketoacidosis: new tricks for old dogs? Intensive Care Med. 2021; 47 (11): 1312–1314. DOI: 10.1007/s00134-021-06527-7. PMID: 34608527

18. Marino P.L. Ed. Yaroshevsky A.I. Intensive therapy. Second edition. Translated from English. M.: GEOTARMedia; 2022: 1152. ISBN 978-5-9704-7041-1

19. Spichak I.I., Kopytova E.V. Application of polyionic reamberin solution in medicine and experience with its use in pediatric oncology. P.A. Herzen Journal of Oncology/ Oncologiya. Zhurnal im. P.A. Herzena. 2018; 7 (5): 47 55. (in Russ.). DOI; 10.17116/onkolog2018705147

20. Tikhonova E.O., Lyapina E.P., Shuldyakov A.A., Sattarova S.A. Use of succinate-containing agents in the treatment of infectious diseases. Ter. Arkh/Terapevticheskiy Arkhiv. 2016; 88 (11): 121–127. (in Russ.). DOI: 10.17116/terarkh20168811121-127

21. Shah B. N., Lapshin V.N., Kyrnyshev A.G., Smirnov D.B., Kravchenko-Berezhnaya N.R. Metabolic effects of a succinic acid. General Reanimatology/Obshchaya Reanimatologya. 2014; 10 (1): 33–42. (in Russ.). DOI: 10.15360/1813-9779-2014-1-33-42