Clinical effectiveness of bioflavonoids in the treatment of secondary lower limb lymphedema

Abstract

AIM: This study aimed to investigate the effectiveness of the application of a combination of the preparation of micronized purified flavonoid fraction (MPFF) and elastic compression in patients with acquired lymphostasis.

MATERIALS AND METHODS: Sixty patients with stage II secondary lower limb lymphedema according to М. Foeldi were included. The patients were divided into two groups through randomization with the envelope method. The first group (n = 30) was subjected to a conservative treatment (MPFF, 1000 mg/day) coupled with elastic compression (3rd class compression stockings). The second group was given compressive therapy (third-class compression stockings). The patients were physically examined through the measurement of the circumference of the limb at different levels.

RESULTS: In the first group, the circumference of the lower third of the shin decreased by 8.15% (p = 0.005) after 1 month and by the end of treatment – by 10.6% (p < 0.001), of the middle third of shin – by 3.15% (p = 0.001) and 4.78% (p < 0.001), and of the upper third–by 4.08% (p < 0.001) and 5.99% (p < 0.001). By the end of the observation period (3 months), the circumference of the lower third of the shin in the second group (29.68 ± 4.67 cm) was significantly greater than that in the first group (26.65 ± 2.92 cm, p = 0.035). No adverse reactions were observed in the MPFF group.

CONCLUSIONS: The volume of the lower limbs of patients with acquired lymphedema decreased after using a combination of MPFF and elastic compression to a larger extent than after the isolated use of elastic compression. Patients taking MPFF had a positive clinical effect without adverse reactions. Therefore, MPFF could be used in the pharmacotherapy of secondary lymphedema of the lower limbs.

Keywords

MOFF / lymphedema / lymphostasis / elephantiasis / bioflavonoids / venotonics / phleboprotectors

References

[1] Elwell R. An overview of the use of compression in lower-limb chronic oedema. British Journal of Community Nursing. 2016;21(1):36,38,40. doi: 10.12968/bjcn.2016.21.1.36

[2] Elwell R. An overview of the use of compression in lower-limb chronic oedema // British Journal of Community Nursing. 2016. Vol. 21, № 1. P. 36, 38, 40. doi: 10.12968/bjcn.2016.21.1.36

[3] Kalinin RE, Suchkov IA, Maksaev DA. Quality of Life of Patients with Secondary Lymphedema of the Lower Extremities. Flebologiya. 2021;15(1):6-12. (In Russ). doi: 10.17116/flebo2021150116

[4] Калинин Р.Е., Сучков И.А., Максаев Д.А. Качество жизни пациентов с вторичной лимфедемой нижних конечностей // Флебология. 2021. Т. 15, № 1. С. 6-12. doi: 10.17116/flebo2021150116

[5] Myshentsev PN, Sushkov SA, Katorkin SE, et al. Diagnostics of Lower Limbs Lymphedema. Flebologiya. 2017;11(4):228-37. (In Russ). doi: 10.17116/flebo2017114228-236

[6] Мышенцев П.Н., Сушков С.А., Каторкин С.Е., и др. Диагностика лимфедемы конечностей // Флебология. 2017. Т. 11, № 4. С. 228-237. doi: 10.17116/flebo2017114228-236

[7] Myshentsev PN, Katorkin SE. Tactics in the treatment of lower limb secondary lymphedema. Novosti Khirurgii. 2014;22(2):239-43. (In Russ).

[8] Мышенцев П.Н., Каторкин С.Е. Тактика лечения при вторичной лимфедеме нижних конечностей // Новости хирургии. 2014. Т. 22, № 2. С. 239-243.

[9] Kalinin RE, Suchkov IA, Maksaev DA. Endothelial dysfunction in patients with secondary lymphedema and methods of its correction (literature review). Nauka Molodykh (Eruditio Juvenium). 2019;7(2):283-93. (In Russ). doi: 10.23888/HMJ201972283-293

[10] Калинин Р.Е., Сучков И.А., Максаев Д.А. Эндотелиальная дисфункция у пациентов с вторичной лимфедемой и способы ее коррекции (обзор литературы) // Наука молодых (Eruditio Juvenium). 2019. Т. 7, № 2. С. 283-293. doi: 10.23888/HMJ201972283-293

[11] Badtieva VA, Apkhanova TV. Lymphedema of the lower extremities: current aspects of combined conservative therapy. Flebologiya. 2010;4(3):55-60. (In Russ).

[12] Бадтиева В.А., Апханова Т.В. Лимфедема нижних конечностей: современные аспекты комплексного консервативного лечения // Флебология. 2010. Т. 4, № 3. С. 55-60.

[13] Savkin ID. Surgical treatment of limb lymphedema. Nauka Molodykh (Eruditio Juvenium). 2013;(4):61-5. (In Russ).

[14] Савкин И.Д. Хирургическое лечение лимфедемы конечностей // Наука молодых (Eruditio Juvenium). 2013. № 4. С. 61-65.

[15] Lulay GR. Lymphedema. Diagnostics and therapy. Der Chirurg. 2013;84(7):607-16. doi: 10.1007/s00104-012-2388-5

[16] Lulay G.R. Lymphedema. Diagnostics and therapy // Der Chirurg. 2013. Vol. 84, № 7. P. 607-616. doi: 10.1007/s00104-012-2388-5

[17] Döller W. Possibilities of surgical therapy of lymphedema. Wiener Medizinische Wochenschrift. 2013;163(7-8):177-83. doi: 10.1007/s10354-013-0202-8

[18] Döller W. Possibilities of surgical therapy of lymphedema // Wiener Medizinische Wochenschrift. 2013. Vol. 163, № 7-8. P. 177-183. doi: 10.1007/s10354-013-0202-8

[19] Yarovenko GV, Myshentsev PN. Comprehensive Treatment of Patients with Lymphedema of the Lower Extremities. Journal of Experimental and Clinical Surgery. 2019;12(4):230-4. (In Russ). doi: 10.18499/2070-478X-2019-12-4-230-234

[20] Яровенко Г.В., Мышенцев П.Н. Комплексное лечение больных лимфедемой нижних конечностей // Вестник экспериментальной и клинической хирургии. 2019. Т. 12, №4. С. 230-234. doi: 10.18499/2070-478X-2019-12-4-230-234

[21] Myshencev PN, Katorkin SE, Lichman LA. A case of successful surgical treatment of a patient with lymphedema of lower limbs. I.P. Pavlov Russian Medical Biological Herald. 2018;26(2):288-95. (In Russ). doi: 10.23888/PAVLOVJ2018262288-295

[22] Мышенцев П.Н., Каторкин С.Е., Личман Л.А. Случай успешного оперативного лечения пациента с лимфедемой нижних конечностей // Российский медико-биологический вестник имени академика И.П. Павлова. 2018. Т. 26, № 2. С. 288-295. doi: 10.23888/PAVLOVJ2018262288-295

[23] Yudin VA, Savkin ID. Treatment of lymphedema limb (review). I.P. Pavlov Russian Medical Biological Herald. 2015;(4):145-53. (In Russ).

[24] Юдин В.А., Савкин И.Д. Лечение лимфедемы конечностей (обзор литературы) // Российский медико-биологический вестник имени академика И.П. Павлова. 2015. № 4. С. 145-153.

[25] Fionik OV, Bubnova NA, Petrov SV, et al. Farmakoterapiya limfedemy. Spravochnik Poliklinicheskogo Vracha. 2007;(10):72-5. (In Russ).

[26] Фионик О.В., Бубнова Н.А., Петров С.В., и др. Фармакотерапия лимфедемы // Справочник поликлинического врача. 2007. № 10. С. 72-75.

[27] Azhar SH, Lim HY, Tan B-K, et al. The Unresolved Pathophysiology of Lymphedema. Frontiers in Physiology. 2020;11:137. doi: 10.3389/fphys.2020.00137

[28] Azhar S.H., Lim H.Y., Tan B.-K., et al. The Unresolved Pathophysiology of Lymphedema // Frontiers in Physiology. 2020. Vol. 11. P. 137. doi: 10.3389/fphys.2020.00137

[29] The Diagnosis and Treatment of Peripheral Lymphedema: 2016 Consensus Document of the International Society of Lymphology. Lymphology. 2016;49(4):170-84.

[30] The Diagnosis and Treatment of Peripheral Lymphedema: 2016 Consensus Document of the International Society of Lymphology // Lymphology. 2016. Vol. 49, № 4. P. 170-184.

[31] Bogucka-Kocka A, Woźniak M, Feldo M, et al. Diosmin — isolation techniques, determination in plant material and pharmaceutical formulations, and clinical use. Natural Product Communications. 2013;8(4):545-50.

[32] Bogucka-Kocka A., Woźniak M., Feldo M., et al. Diosmin — isolation techniques, determination in plant material and pharmaceutical formulations, and clinical use // Natural Product Communications. 2013. Vol. 8, № 4. P. 545-550.

[33] Yarovenko GV, Katorkin SE, Myshentsev PN. Limfedema. 2nd ed. Samara: IE Nikiforov M.V.; 2020. (In Russ).

[34] Яровенко Г.В., Каторкин С.Е., Мышенцев П.Н. Лимфедема. 2-е изд. Самара: ИП Никифоров М.В.; 2020.

[35] Shishlo VK, Malinin AA, Dyurzhanov AA. Mechanisms of antioedemic effect of bioflavonoids in experiment. Angiology and Vascular Surgery. 2013;19(2):25-33. (In Russ).

[36] Шишло В.К., Малинин А.А., Дюржанов А.А. Механизмы противоотечного воздействия биофлавоноидов в эксперименте // Ангиология и сосудистая хирургия. 2013. Т. 19, № 2. С. 25-33.

[37] Klimenko DA, Kvetenadze TE, Mashimbayev EK, et al. Rol’ flavonoidov v stimulyatsii rezorbtsionnoy funktsii limfaticheskoy sistemy v eksperimente. Vestnik Limfologii. 2009;(4):22-7. (In Russ).

[38] Клименко Д.А., Кветенадзе Т.Е., Машимбаев Е.К., и др. Роль флавоноидов в стимуляции резорбционной функции лимфатической системы в эксперименте // Вестник лимфологии. 2009. № 4. С. 22-27.

[39] Kalinin RE, Suchkov IA, Mnikhovich MV, et al. Endothelial effects of the micronized purified flavonoid fraction in various experimental models of venous endothelial dysfunction. Flebologiya. 2014;8(4):29-36. (In Russ).

[40] Калинин Р.Е., Сучков И.А., Мнихович М.В., и др. Эндотелиотропные эффекты микронизированной очищенной фракции флавоноидов при различных экспериментальных моделях венозной эндотелиальной дисфункции // Флебология. 2014. Т. 8, № 4. С. 29-36.

[41] Borodin YuI, Lyubarskiy MS, Morozov VV. Rukovodstvo po klinicheskoy limfologii. Moscow: MIA; 2010. (In Russ).

[42] Бородин Ю.И., Любарский М.С., Морозов В.В. Руководство по клинической лимфологии. М.: МИА; 2010.

[43] Fionik OV, Bubnova NA, Petrov SV, et al. Limfedema nizhnikh konechnostey: algoritm diagnostiki i lecheniya. Novosti Khirurgii. 2009; 17(4):49-64. (In Russ).

[44] Фионик О.В., Бубнова Н.А., Петров С.В., и др. Лимфедема нижних конечностей: алгоритм диагностики и лечения // Новости хирургии. 2009. Т. 17, № 4. С. 49-64.

[45] Sander AP, Hajer NM, Hemenway K, et al. Upper-extremity volume measurements in women lymphedema: a comparison of measurements obtained via water displacement with geometrically determined volume. Physical Therapy. 2002;82(12):1201-12.

[46] Sander A.P., Hajer N.M., Hemenway K., et al. Upper-extremity volume measurements in women lymphedema: a comparison of measurements obtained via water displacement with geometrically determined volume // Physical Therapy. 2002. Vol. 82, № 12. P. 1201-1212.

[47] Valsamis JB, Vankerckhoves S, Vandermeeren L, et al. Measurement of lymphedema: pythagoras vs archimedes vs high-tech. European Journal of Lymphology. 2016;28(74):53.

[48] Valsamis J.B., Vankerckhove S., Vandermeeren L., et al. Measurement of lymphedema: pythagoras vs archimedes vs high-tech // European Journal of Lymphology. 2016. Vol. 28, № 74. P. 53.

[49] Michelini S, Fiorentino A, Cardone M. Melilotus, Rutin and Bromelain in primary and secondary lymphedema. Lymphology. 2019;52(4):177-86.

[50] Michelini S., Fiorentino A., Cardone M. Melilotus, Rutin and Bromelain in primary and secondary lymphedema // Lymphology. 2019. Vol. 52, № 4. P. 177-186.

[51] Casley-Smith JR, Casley-Smith JR. The effects of diosmin (a benzo-pyrone) upon some high-protein oedemas: lung contusion, and burn and lymphoedema of rat legs. Agents and Actions. 1985;17(1):14-20. doi: 10.1007/BF01966674

[52] Casley-Smith J.R., Casley-Smith J.R. The effects of diosmin (a benzo-pyrone) upon some high-protein oedemas: lung contusion, and burn and lymphoedema of rat legs // Agents and Actions. 1985. Vol. 17, № 1. P. 14-20. doi: 10.1007/BF01966674

[53] Casley-Smith JR, Casley-Smith JR. Treatment of Lymphedema by Complex Physical Therapy, with and without oral and topical benzopyrones. Lymphology.1996;29(2):76-82.

[54] Casley-Smith J.R., Casley-Smith J.R. Treatment of Lymphedema by Complex Physical Therapy, with and without oral and topical benzopyrones // Lymphology. 1996. Vol. 29, № 2. P. 76-82.

[55] Pecking AP, Février B, Wargon C, et al. Efficacy of Daflon 500 mg in the treatment of lymphedema (secondary to conventional therapy of breast cancer). Angiology. 1997;48(1):93-8. doi: 10.1177/000331979704800115

[56] Pecking A.P., Février B., Wargon C., et al. Efficacy of Daflon 500 mg in the treatment of lymphedema (secondary to conventional therapy of breast cancer) // Angiology. 1997. Vol. 48, № 1. P. 93-98. doi: 10.1177/000331979704800115

RIGHTS & PERMISSIONS

Kalinin R.E., Suchkov I.A., Maksaev D.A.