Efficacy of Phlebotonics in the Perioperative Period for Open Hemorrhoidectomy: A Single-Center Randomized Clinical Trial

Background. The use of phlebotonics in the postoperative period after hemorrhoidectomy has already proven effective in preventing postoperative complications. However, the initiation of phlebotonics in the preoperative period is covered in only a few publications in modern literature.

Aim: to evaluate the effect of phlebotonics on the postoperative course after open hemorrhoidectomy for stage II–IV haemorrhoidal disease when used both before and after surgery.

Material and methods. The study was a randomized controlled trial and included 60 patients with stage III–IV haemorrhoidal disease: in the main group (n = 30), phlebotonics (hesperidin 100 mg + diosmin 900 mg, Venarus®) were started 10 days before surgery at a dosage of 1000 mg once daily and continued after surgery according to the scheme: 1000 mg twice daily on days 1–7, then 1000 mg once daily on days 8–14; in the control group (n = 30), phlebotonics were started only after surgery and administered according to the protocol for acute hemorrhoids. The primary endpoint was the frequency of edema and thrombosis of the mucocutaneous bridges by day 14 after surgery. Secondary endpoints were pain intensity according to VAS, the presence of postoperative bleeding, the patient's quality of life according to the validated SF-36 questionnaire, the speed of postoperative wound healing, and the time to return to daily physical activity.

Results. The groups were comparable in terms of baseline characteristics; no significant differences in age, sex, BMI, disease stage, or main clinical manifestations of haemorrhoidal disease were recorded. Edema of the mucocutaneous bridges in the main group by day 21 after surgery was significantly lower compared to the control group (p = 0.05). No significant differences in bleeding between days 1 and 7 postoperatively were noted between the groups; however, a statistically significant reduction in discharge in the main group was observed in the second and third weeks after surgery (p = 0.03 and p = 0.02, respectively). The intensity of pain, starting from the first day and throughout the three weeks after surgery, was significantly lower in the main group (p ≤ 0.05). Patients in the main group had a faster return to daily physical activity and significantly faster healing of postoperative wounds, confirmed by the SF-36 questionnaire results in terms of social functioning, mental health, physical functioning, and general health (p = 0.05). On day 60 after surgery, residual perianal skin tags causing hygiene issues and discomfort were found in only 2 (7 %) patients of the first main group and 5 patients (17 %) of the second group (p = 0.4).

Conclusions. The use of phlebotonics in patients before and after open hemorrhoidectomy, compared to use only in the postoperative period, demonstrates statistically significant efficacy in preventing the development of edema of the mucocutaneous bridges and reducing pain syndrome.

1. Zagriadskiy E.A., Bogomazov A.M., Golovko E.B., Abritsova M.V. Influence of treatment methods on quality of life of patients with hemorrhoidal disease. Ambulatornaya khirurgiya = Ambulatory Surgery (Russia). 2022;19(1):68–80. (In Russ.). DOI: 10.21518/1995-1477-2022-19-1-68-80

2. Zagryadskiy E.A., Bogomazov A.M., Golovko E.B. Conservative treatment of hemorrhoids. An alternative to surgical methods or components? Chorus program results. Koloproktologia. 2018;35(1):27–35. (In Russ.). DOI: 10.33878/2073-7556-2018-0-1-27-35

3. Nelson R.L., Abcarian H., Davis F.G., Persky V. Prevalence of benign anorectal disease in a randomly selected population. Dis Colon Rectum. 1995;38(4):341–4. DOI: 10.1007/BF02054218

4. Garg P., Singh P. Adequate dietary fiber supplement and TONE can help avoid surgery in most patients with advanced hemorrhoids. Minerva Gastroenterol Dietol. 2017;63(2):92–6. DOI: 10.23736/S1121-421X.17.02364-9

5. Garg P., Tulina I., Ren D.L., Bhattacharya K., Yagnik V.D., Mahak G. TONEFACT: Can even advanced hemorrhoids be treated without surgery? A paradigm shift in the management of hemorrhoids. World J Gastrointest Surg. 2025;17(7):107099. DOI: 10.4240/wjgs.v17.i7.107099

6. Johanson J.F., Sonnenberg A. The prevalence of hemorrhoids and chronic constipation. An epidemiologic study. Gastroenterology. 1990;98(2):380–6. DOI: 10.1016/0016-5085(90)90828-o

7. Yeo D., Tan K.Y. Hemorrhoidectomy — making sense of the surgical options. World J Gastroenterol. 2014;20(45):16976–83. DOI: 10.3748/wjg.v20.i45.16976

8. Lohsiriwat V. Treatment of hemorrhoids: A coloproctologist’s view. World J Gastroenterol. 2015;21(31):9245–52. DOI: 10.3748/wjg.v21.i31.9245.

9. Aibuedefe B., Kling S.M., Philp M.M., Ross H.M., Poggio J.L. An update on surgical treatment of hemorrhoidal disease: a systematic review and meta-analysis. Int J Colorectal Dis. 2021;36(9):2041–9. DOI: 10.1007/s00384-021-03953-3

10. Clinical guidelines of the Ministry of Health of the Russian Federation “Hemorrhoids”, 2024 (In Russ.). URL: https://cr.minzdrav.gov.ru/preview-cr/178_2

11. Serafini M., Peluso I., Raguzzini A. Flavonoids as antiinflammatory agents. Proc Nutr Soc. 2010;69(3):273–8. DOI: 10.1017/S002966511000162X

12. Davis B.R., Lee-Kong S.A., Migaly J., Feingold D.L., Steele S.R. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Hemorrhoids. Dis Colon Rectum. 2018;61(3):284–92. DOI: 10.1097/DCR.0000000000001030

13. Berkoz M. Diosmin suppresses the proinflammatory mediators in lipopolysaccharide-induced RAW264.7 macrophages via NF-κB and MAPKs signal pathways. Gen Physiol Biophys. 2019;38(4):315–24. DOI: 10.4149/gpb_2019010

14. Shalkami A.S., Hassan M., Bakr A.G. Anti-inflammatory, antioxidant and anti-apoptotic activity of diosmin in acetic acid-induced ulcerative colitis. Hum Exp Toxicol. 2018;37(1):78–86. DOI: 10.1177/0960327117694075

15. Choi I.Y., Kim S.J., Jeong H.J., Park S.H., Song Y.S., Lee J.H., et al. Hesperidin inhibits expression of hypoxia inducible factor-1 alpha and inflammatory cytokine production from mast cells. Mol Cell Biochem. 2007;305(1– 2):153–61. DOI: 10.1007/s11010-007-9539-x

16. Shikh E.V., Haitovich E.D. Original clinical and pharmacological effects of hesperidin in the treatment of chronic venous diseases. Lechebnoye delo. 2023;4:17–31 (In Russ.). DOI: 10.24412/2071-5315-2023-13018

17. Godeberge P., Sheikh P., Lohsiriwat V., Jalife A., Shelygin Y. Micronized purified flavonoid fraction in the treatment of hemorrhoidal disease. J Comp Eff Res. 2021;10(10):801–13. DOI: 10.2217/cer-2021-0038

18. Rabelo F.E.F., Lacerda-Filho A., Mansur E.S., de Oliveira F.H., de Queiroz F.L., França-Neto P.R., et al. Benefits of flavonoid and metronidazole use after excisional hemorrhoidectomy: a randomized double-blind clinical trial. Tech Coloproctol. 2021;25(8):949–55. DOI: 10.1007/s10151-021-02465-0

19. La Torre F., Nicolai A.P. Clinical use of micronized purified flavonoid fraction for treatment of symptoms after hemorrhoidectomy: Results of a randomized, controlled, clinical trial. Dis Colon Rectum. 2004;47(5):704–10. DOI: 10.1007/s10350-003-0119-1

20. Medkova Y.S., Tulina I., Yudina V., Abdullaev R., Shcherbakova V., Novikov I., et al. Efficacy of micronized purified flavonoid fraction in the posthemorrhoidectomy period trial: Open-label randomized controlled trial. Dis Colon Rectum. 2024;67(6):826–33. DOI: 10.1097/DCR.0000000000003211

21. Titov A.Yu., Nekhrikova S.V., Veselov A.V. Medicamental therapy in the treatment of postoperative wounds perineum and anal canal. Koloproktologia. 2018;1:7–12 (In Russ.). DOI: 10.33878/2073-7556-2018-0-1-7-12

22. Orefice R., Litta F., Parello A., De Simone V., Campenni P., Marra A.A., et al. A Prospective study on the efficacy of two different phlebotonic therapies as a bridge to surgery in patients with advanced hemorrhoidal disease. J Clin Med. 2021;10(8):1549. DOI: 10.3390/jcm10081549

23. Wang X., Ji X. Sample size estimation in clinical research. Chest. 2020;158(1S):S12–20. DOI: 10.1016/j.chest.2020.03.010

24. Pitesa R., Yuen W.Y.R., Hill A.G. Flavonoids and post haemorrhoidectomy recovery: A systematic review and meta-analysis. ANZ J Surg. 2024;94(9):1480–90. DOI: 10.1111/ans.19116

25. Chiaretti M., Fegatelli D.A., Pappalardo G., Venti M.D.S., Chiaretti A.I. Comparison of centella with flavonoids for treatment of symptoms in hemorrhoidal disease and after surgical intervention: A randomized clinical trial. Sci Rep. 2020;10(1):8009. DOI: 10.1038/s41598-020-64772-0