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| 번호 | 제목 | 등록일 | 조회수 |
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| 140 | Clinical Use of Micronized Purified Flavonoid Fraction for Treatment of Symptoms After Hemorrhoidectomy: Results of a Randomized, Controlled, Clinical Trial [2004년 5월 DCR] | 2011-12-23 | 3642 |
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F. La Torre, M.D., A. P. Nicolai, M.D.
Department of Surgical Sciences, Universita` degli Studi di Roma “La Sapienza”, Policlinico Umberto I, Rome, Italy PURPOSE: The aim of this study was to evaluate if the combination of micronized purified flavonoid fraction with short-term routine antibiotic and anti-inflammatory therapy was better at reducing the intensity of postoperative symptoms and wound bleeding after a Milligan-Morgan’s open hemorrhoidectomy than antibiotic and anti-inflammatory treatment alone.
METHODS: Fifty patients were randomly assigned to receive routine antibiotic and anti-inflammatory treatment alone (control patients) or a combination of micronized purified flavonoid fraction with identical antibiotic and anti-inflammatory treatment (micronized purified flavonoid fraction patients). The evolution of symptoms (pain, tenesmus, pruritus, and bleeding) during the postoperative period was assessed by means of patients’ self-questionnaires. Each symptom was scored on a graded severity scale from 0 to 3, daily during the first three days of the immediate postoperative period, then at regular intervals (about every 14 days) until postoperative day 60. A global score for evaluation of each postoperative symptom and bleeding was used. The global score for each symptom was the sum of scores for each patient over the study period. The global score for each symptom was compared between the two groups with the Mann-Whitney U test.
RESULTS: No significant differences in age, gender distribution, and stage of disease between the two groups were noticed at baseline. Posthemorrhoidectomy symptoms were relieved more rapidly in the micronized purified flavonoid fraction group; during the first three postoperative days, the global score for
each symptom was significantly more reduced in the micronized purified flavonoid fraction group. The global scores for each symptom are as follows: pain after 3 days, 6.16 (SD = 1.9) in the control group vs. 3.48 (SD = 1.8) in the micronized purified flavonoid fraction group (P < 0.0001); tenesmus, 5.36 (SD = 1.8) in the control group vs. 1.48 (SD = 1.5) in the micronized purified flavonoid fraction group (P < 0.0001); pruritus, 4.04 (SD = 1.9) in the control group vs. 1.84 (SD = 1.4) in the micronized purified flavonoid fraction group (P < 0.0001); bleeding, 4.4 (SD = 2.1) in the control group vs. 2.0 (SD = 1.3) in the micronized purified flavonoid fraction group (P < 0.0001). A significant difference (P < 0.0001) between groups was also shown in favor of micronized purified flavonoid fraction patients when global scores were calculated over the entire study period (60 days). CONCLUSION: Micronized purified flavonoid fraction used in combination with short-term antibiotic
and anti-inflammatory treatment can reduce both the duration and extent of postoperative symptoms and wound bleeding following hemorrhoidectomy. Ho et al. have shown that the administration of a micronized purified flavonoid fraction (MPFF) at the
initial daily dose of 3 g (1 g t.i.d.) for three days and then 1.5 g/day (500 mg t.i.d.) for four days lessens the risk of secondary hemorrhage between day 7 and day 15 following pedicular hemorrhoidectomy with a standardized diathermy excision. The effectiveness of MPFF for treating symptoms of patients with hemorrhoidal disease has been widely established, for either acute episodes or as long-term treatment. MPFF is a semisynthetic micronized preparation of the -benzopyrone family, consisting of 90 percent diosmine and 10 percent flavonoids expressed as hesperidine (Arvenum 500®, Alvenor®, Ardium®, Capiven®, Daflon® 500 mg, Detralex®, Elatec®, Flebotropin®, Variton®, Venitol®). Micronization is a well-established technique that allows higher absorption of active compounds from the human gastrointestinal tract. This capability provides a rational explanation for the significantly greater reduction (by 83 percent) of experimentally induced capillary hyperpermeability by MPFF. As a result, the inflammatory process is inhibited and edema subsequently reduced. The superiority of anti-inflammatory action of MPFF over that of other flavonoids explains its clinical superiority in reducing pain and frequency of attacks in patients with hemorrhoids. MPFF improves venous tone and reinforces capillary resistance. This protective effect on capillary fragility may prevent postoperative bleeding. In addition, MPFF increases lymphatic drainage and protects the microcirculation from inflammatory mediators, resulting in reduced edema and pain. This “edema-protective” effect of the drug may have a favorable influence on postoperative symptoms. The drug has an excellent safety profile, as documented by both animal and clinical toxicological studies. Because of its many actions, MPFF has been chosen for the present study.
DISCUSSION
It could be postulated that a third group of patients without any pharmacological treatment would have enhanced the value of this trial. However, the aim of this trial was to demonstrate that the addition of MPFF to routine postoperative treatment (antibiotic plus NSAID) is better at reducing postoperative pain,
bleeding, and other symptoms related to hemorrhoidectomy than short-term postoperative treatment alone. According to different consensus papers, the treatment of postoperative morbidity, particularly postoperative pain, is based essentially on peripheral analgesics, NSAIDs, and morphine. Moreover, prophylactic antibiotherapy with metronidazole has been previously shown to reduce postoperative pain between Day 5 and Day 7 after surgery, to increase patients’ satisfaction, and to allow them to return to work earlier. In our study, this routine treatment based on both antibiotic and NSAID proved to be effective according to Friedman’s tests performed in both groups. Comparison of symptom GS regression between the MPFF and control groups (Mann-Whitney U test) confirmed that the addition of MPFF to postoperative antibiotic and anti-inflammatory treatment reduced the extent of posthemorrhoidectomy symptoms typified by pain, pruritus, tenesmus, and bleeding. This reinforces data found in previous clinical trials using varying dosages and of different study lengths, in which MPFF was more effective than placebo in reducing the duration and intensity of symptoms (e.g., bleeding, pain, and anal discharge) of acute hemorrhoid attacks. Bleeding from nonprolapsed internal hemorrhoids resolved more quickly with MPFF plus fiber than with fiber alone. In the same study, the efficacy of MPFF in treating acute bleeding related to internal hemorrhoids has been shown to be equal to that of a well-established surgical technique, rubber band ligation. The frequency and duration of relapses of acute hemorrhoidal symptoms were reduced with long-term MPFF treatment in patients with chronic hemorrhoids. In pregnant women, short-term treatment with MPFF alleviated symptoms of hemorrhoids (bleeding, pain, rectal discomfort, and rectal exudation) from baseline by 66 percent. Moreover, in a prospective, randomized, controlled trial of MPFF to reduce bleeding after surgery, Ho et
al. showed that the risk of secondary bleeding from hemorrhoidectomy decreased with postoperative MPFF treatment. According to the authors of these previous trials, the efficacy of MPFF in alleviating symptoms and bleeding in acute internal hemorrhoidal attacks and preventing recurrent attacks may be attributable to its phlebotropic activity, its protective effect against the capillary fragility, and its antiinflammatory effect. These different actions imply that MPFF is an “edema-protective” drug in treatment of acute hemorrhoids. It has been hypothesized that the positive effect of MPFF on anal mucosa is through decreasing the edema. The anti-inflammatory effect of MPFF protects the hemorrhoidectomy wound from progressing to a friable state. Therefore, the wound is less vulnerable to bacterial fibrinolysis and defecation stress and the risk of secondary hemorrhage is reduced. In our study, no secondary hemorrhage occurred after the seventh postoperative day, even though 88
percent of patients reported bleeding from the first day after surgery. Almost all patients had other symptoms at Day 1 (pain, 98 percent; pruritus, 82 percent; and tenesmus, 70 percent), and from as early as the third postoperative day until the 25th, symptom improvement became significant and was better with MPFF. Follow-up examinations showed a faster wound-healing process, a lower degree of perianal edema, and less secretion in the MPFF group than in the control group. |
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