Experimental Justification of the Use of Colloidal Blood Substitutes for Fat Globulemia

The purpose of the study is to assess in vitro the effect of colloidal blood substitutes on fat globules in the blood of patients with severe polytrauma.

Materials and methods. Perftoran, 5% albumin solution, dextran-40, dextran-60, modified gelatin, hydroxyethyl starches 200/0.5 and 130/0.42 were added to the blood of 19 patients with severe polytrauma at ratios 1:20, 1:10, 1:5 and 1:3, respectively, which corresponded to the addition of 0.015 ml, 0.03 ml, 0.06 ml, 0.1 ml of the blood substitute under test to 0.3 ml of blood in a tube. Microscopy of the samples with assessment of the number and area of fat globules was carried out using a transmitted-light medical microvisor mVizo-101 (LOMO, Russia) 30 minutes after the blood and blood substitute exposure and subsequent staining with Sudan IV. The findings were processed using JMicroVision 1.2.7 software.

Results. Dextran-60, hydroxyethyl starch 200/0.5 and 130/0.42 in vitro lead to a decrease in fat globules in the blood of patients with severe polytrauma in proportion to the dilution degree. Modified gelatin, dextran-40, 5% albumin solution and Perftoran have a significant additional emulsifying effect on the fat globules. The maximum emulsifying effect was obtained after addition of Perftoran to the blood.

Conclusion. The experimental data on the effect of 5% albumin solution, modified gelatin, dextran-40, and Perftoran on fat globules justify the prospect for their further clinical application for prevention and treatment of fat embolism in an extended clinical trials.

1. Kwiatt M.E., Seamon M.J. Fat embolism syndrome. Int. J. Crit. Illn. Inj. Sci. 2013; 3 (1): 64–68. DOI: 10.4103/2229-5151.109426. PMID: 23724388

2. Kosova E., Bergmark B., Piazza G. Fat embolism syndrome. Circulation. 2015; 131 (3): 317-320. DOI: 10.1161/CIRCULATIONAHA.114.010835. PMID: 25601951

3. George J., George R., Dixit R., Gupta R.C., Gupta N. Fat embolism syndrome. Lung India. 2013; 30 (1): 47-53. DOI: 10.4103/0970-2113.106133. PMID: 23661916

4. Cárdenas-Camarena L., Gerardo L. P. A., Durán H., Bayter-Marin J. E. Strategies for reducing fatal complications in liposuction. Plast. Reconstr. Surg. Glob. Open. 2017; 5 (10): e1539. DOI: 10.1097/GOX.0000000000001539. PMID: 29184746

5. Dhakal L.P., Bourgeois K., Barrett K.M., Freeman W.D. The “starfield” pattern of cerebral fat embolism from bone marrow necrosis in sickle cell crisis. Neurohospitalist. 2015; 5 (2): 74-76. DOI: 10.1177/1941874414554300. PMID: 25829988

6. Zenker F.A. Beitragezuranatomie und physiologie der lunge. J. Braunsdorf. 1861.

7. Lehman E.P., Moore R.M. Fat embolism, including experimental production without trauma. Arch. Surg. 1927; 14: 621. DOI: 10.1001/archsurg.1927.01130150002001

8. Agarwal A.K., Sen R., Tripathy S.K., Aggarwal S., G N., Gupta D. Is there any role of inhalational corticosteroids in the prophylaxis of post-traumatic fat embolism syndrome? Cureus. 2015; 7 (9): e332. DOI: 10.7759/cureus.332. PMID: 26543690

9. Sen R.K., Tripathy S.K., Krishnan V. Role of corticosteroid as a prophylactic measure in fat embolism syndrome: a literature review. Musculoskelet Surg. 2012; 96 (1): 1-8. DOI: 10.1007/s12306-011-0156-1. PMID: 21773697

10. Sen R.K., Prakash S., Tripathy S.K., Agarwal A., Sen I.M. Inhalational Ciclesonide found beneficial in prevention of fat embolism syndrome and improvement of hypoxia in isolated skeletal trauma victims. Eur. J. Trauma Emerg. Surg. 2016; 43 (3): 313-318. DOI: 10.1007/s00068-0160633-1. PMID: 26781645

11. Liu X.M., Huang J.C., Wang G.D., Lan S.H., Wang H.S., Pan C.W., Zhang J.P., Cai X.H. Clinical effectiveness analysis of dextran 40 plus dexamethasone on the prevention of fat embolism syndrome. Int. J. Clin. Exp. Med. 2014; 7 (8): 2343-2346. PMID: 25232433

12. Plakhotina E.N., Bocharov S.N., Tvorogova S.S., Dmitrieva L.A., Rodionova L.V., Kinash I.N. The effectiveness of experimental fat embolism treatment with preparations more often used in clinical practice. Byulleten VSNTs SO RAMN. 2005; 6: 157—161. [In Russ.]

13. Li S., Zou D., Qin Z., Liu N., Zhang J., Li Z., Shao Y., Deng K., Chen Y., Huang P. Non fracture-associated pulmonary fat embolism after blunt force fatality: case report and review of the literature. Am. J. Forensic. Med. Pathol. 2015; 36 (2): 61–65. DOI: 10.1097/PAF.0000000000000142. PMID: 25651164

14. Pevnev A.A., Belous M.S., Chistyakov S.I., Yakovlev A.Yu.. In vitro effect of colloid infusion solutions on fat globules. Sovremennye Tekhnologii v Meditsine. 2016; 8 (4): 306-308. [In Russ.]

15. Titov V.N., Rozhkova T.A., Amelyushkina V.A. Fatty acids, triglycerides, hypertriglyceridemia, hyperglycemia and insulin (pathogenesis, diagnosis and treatment). Moscow: Infra-M; 2016: 198. ISBN 978-5-16011325-8. [In Russ.]

16. Rafikova O., Sokolova E., Rafikov R., Nudler E. Control of plasma nitric oxide bioactivity by perfluorocarbons: physiological mechanisms and clinical implications. Circulation. 2004; 110 (23): 3573–3580. DOI: 10.1161/01.CIR.0000148782.37563.F8. PMID: 15557364

17. Rafikova O., Rafikov R., Nudler E. Catalysis of S-nitrosothiols formation by serum albumin: the mechanism and implication in vascular control. Proc. Natl. Acad. Sci. USA. 2002; 99 (9): 5913–5918. DOI: 10.1073/pnas.092048999. PMID: 11983891

18. Moroz V.V., Molchanova L.V., Gerasimov L.V., Ostapchenko D.A., Yershova L.I., Likhovetskaya Z.M., Gorbunova N.A. Blood rheological and hemolytic effects of perfluorane in patients with severe injury and blood loss. Obshchaya Reanimatologiya = General Reanimatology. 2006; 2 (1): 5-11. DOI: 10.15360/1813-9779-2006-1-5-11. [In Russ., In Engl.]

19. Moroz V.V., Ryzhkov I.A. Acute blood loss: regional blood flow and microcirculation (review, part I). Obshchaya Reanimatologiya = General Reanimatology. 2016; 12 (2): 66-89. DOI: 10.15360/1813-9779-2016-256-65. [In Russ., In Engl.]

20. Moroz V.V., Novoderzhkina I.S., Afanasyev A.V., Zarzhetsky Y.V., Ryzhkov I.A., Kozlova E.K., Chernysh A.M. Effect of perftoran on membrane nanostructure of discocyte and stomatocyte after acute blood loss. Obshchaya Reanimatologiya = General Reanimatology. 2017; 13 (2): 32-39. DOI: 10.15360/1813-9779-2017-2-32-39. [In Russ., In Engl.]