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Department of Surgery, Dammam Central Hospital, Dammam, Eastern Province, Saudi Arabia

Correspondence to: A-W. N. Meshikhes, P O Box 18418, Qatif 31911, Saudi Arabia Email: meshikhes@doctor.com

Introduction

Materials and Methods

Results

Discussion

References

Keywords: Daflon, haemorrhoids, medical treatment, surgery Surg J R Coll Surg Edinb Irel., 1 December 2004, 335-338

Background: Daflon, a phlebotropic agent, is of proven efficacy in the treatment of various venous disorders. Although it has been tried in the treatment of haemorrhoids, its efficacy in alleviating various haemorrhoidal symptoms has not been assessed properly. The aim of this study was to confirm the efficacy of Daflon in the treatment of haemorrhoidal symptoms. Methods: Two hundred and sixty eight patients presenting with haemorrhoidal symptoms were recruited. This was a multicentre non-randomised observational study with no placebo arm. After establishing the extent of their symptoms and determining the position, size and degree of haemorrhoids by proctoscopy, all patients were started on Daflon, four tablets per day, in two divided doses for four weeks. Patients were seen weekly during the study period and carefully questioned as regard to symptoms, and a proctoscopy was carried out. Results: There was a statistically significant improvement (p<0.001) in all haemorrhoidal symptoms (pain, heaviness, bleeding, pruritus and anal discharge) and in the proctoscopic appearance of the ‘piles,’ comparing baseline visit findings with the last visit four weeks after treatment with Daflon. Conclusions: Daflon has been shown to be effective in alleviating (variable degree) haemorrhoidal symptoms and improving the proctoscopic appearance of haemorrhoids. Therefore, it should be considered initially for patients presenting with haemorrhoidal symptoms. However, prospective randomised trials and longer follow-up are needed to confirm the findings of this study and delineate more precisely the role of Daflon in the management of haemorrhoidal disease

Haemorrhoidal disease is a common anorectal condition affecting many individuals throughout the world. There are many treatment options available depending on the degree of the haemorrhoidal disorder. Nevertheless, the best treatment is prevention; by avoiding constipation, intake of high fibre diet and administration of bulk laxatives. Local symptoms can be alleviated by some soothing creams and suppositories, but longterm benefit is not often achieved. Nonsurgical treatment modalities such as rubber band ligation, injection sclerotherapy (using 5% phenol in almond oil), photocoagulation and cryotherapy are well established and acceptable to patients. However, they are not suitable for all grades of ‘piles’ and have recognised complications.^1-3 On the other hand, surgical haemorrhoidectomy is associated with a significant morbidity and may lead to delays in return to work.^3,4 Therefore, provision of a medical treatment that is easy to administer, free of any significant complications and reduces the likelihood of surgery would be attractive to patients and surgeons alike.

Daflon (Les Laboratoires Servier, Orleans, France) is a flavonoid vasoprotector venotonic agent whose active component is micronized flavonidic fraction that contains flavonoid extracts of rutaceae, equivalent to 150mg diosmin expressed as hesperidine. It is a phlebotrophic agent that has a proven efficacy in the treatment of various venous disorders.^3,5 It has also been used in the past to reduce the risk of post-operative secondary bleeding from haemorrhoidectomy.6 Daflon has been used in the past for the treatment of haemorrhoids with a reported favourable outcome.^3,5 Its use, however, has been challenged and overshadowed by various non-operative therapeutic modalities such as sclerotherapy and rubber band ligation. Thus, its use has become uncommon in the daily practice of general practitioners in health centres and in general surgical clinics. The following study was conducted to confirm its efficacy and safety in the management of patients with this troublesome condition and reassess its utilisation as a valuable treatment option readily available to general practitioners.

A multi-centre observational clinical study was designed to involve five major hospitals in three provinces of the Kingdom of Saudi Arabia (Central, Western and Eastern). This was a non-randomised and non-placebo controlled study. Inclusion criteria were based on the symptoms and physical signs documented in the patients. Symptomatic criteria were pain (including discomfort and tensemus during or other than at the time of defecation), heaviness, bleeding, pruritus and mucus discharge. Physical signs were determined objectively by prosctoscopy. The study included 268 patients who were attending the clinics for the first time and were presenting with haemorrhoidal problems. All patients were interviewed in a detailed way, recording their age, sex, duration of the present episode, bowel habits, previous treatments and presence of any associated medical diseases. A proctoscopic examination was also conducted to establish the size, site and degree of the ‘piles’. Patients with thrombosed haemorrhoids were subjected to incision and evacuation at the time of the first examination and excluded from the study. All gave their consent prior to inclusion in the study and were started on four Daflon tablets (each 250 mg) per day in two divided doses for four weeks. All were treated on an outpatient basis and were seen weekly over the study period and carefully questioned as regard to symptoms in an attempt to score their severity and any side effects of treatment that might have occurred. Pain was assessed by using a pain score ranging from 0 (no pain) to 10 (worst pain). Similar scoring systems were adopted for heaviness, pruritus and anal discharge. A symptom score of 8-10 was regarded as severe, 5-7 was scored as moderate, 1-5 was mild and no symptoms was scored zero. The severity of bleeding was assessed by the number of bleeding episodes per day over a given week, before and after treatment. Bleeding was considered severe if it occurred more than five times a week, moderate if three to five times per week and mild if less than three times per week. Proctoscopic examination was conducted at each consultation and findings of size (small, medium or large) and position of the haemorrhoids were carefully recorded. Results were analysed and statistical analyses, comparing symptoms and proctoscopic findings at first (baseline) visit and at the last visit after four weeks of treatment with Daflon, were carried out using the Wilcoxon Signed Ranks test and the Chi-squared test. The study was approved by the Credential and Scientific Research Committees of the participating centres.

A total of 268 patients (169 males and 99 females) were recruited over the study period (December 2000 - May 2001). The mean age was 36 (range 15-84) years. In the initial baseline assessment, 185 patients (69%) presented with their first episode within 12 months, 43 (16%) within 1-2 years and 40 (15%) more than two years following development of symptoms. Constipation was a major complaint in 177 patients (66%), while 72 (27%) had a normal bowel habit and 19 (7%) had a change in bowel habit. Of those entered in the study, 145 patients (54%) had already received some local anti-haemorrhoidal agents in the past without improvement, 102 (38%) were already on laxatives and 13 patients (5%) had some form of previous surgery for their haemorrhoids. Seventy patients (26%) were anaemic, 16 (6%) were obese and five had proctitis. There were three pregnant females and three had an associated anal fissure. Other associated diseases were hypertension, Behcet disease, diabetes and ischaemic heart disease, one each respectively. Results were assessed as shown in Table 1.

There was significant improvement (p<0.001) in the severity of all haemorrhoidal symptoms (pain, heaviness, bleeding, pruritus anal discharge) at the last visit (four weeks treatment), compared with symptoms at presentation during the baseline visit (Table 1).

The size of the haemorrhoids on proctoscopy was assessed as small in 51% of cases and 53% of patients had second degree piles. The most common position for haemorrhoids in the study population was at 3, 7 and 11 o’clock position (21%) followed by 5, 7 and 11 o’clock positions (17%). Congested ‘piles’ were present in 166 (62%) patients. This was relieved in 140 patients (84%) after four weeks of treatment.

Based on the assessment of symptoms and proctoscopic findings, 37% (n=99) had excellent improvement, 48% (n=127) had good results, 12% (n=32) had moderate results and 3% (n=8) had no improvement.

Side effects of Daflon were documented in eight patients (3%) but did not interrupt the study medication. Five patients complained of minor gastrointestinal symptoms, two of renal colic-like pain and one experienced mild palpitation.

Haemorrhoidal disease is a common affliction, particularly in the Saudi population. Studies into the aetiology and incidence of haemorrhoids in Saudi Arabia are lacking, but they are believed to be due to an underlying genetic predisposition. Toilet habits, chronic constipation and a westernized diet are believed to be common contributing factors. In the author’s institute, an average of 120 haemorrhoidectomies are carried out each year making it the third most common elective surgical procedure after cholecystectomy and hernia repair (unpublished hospital statistics).

This study is a prospective multi-centre observational study and was conducted in five major hospitals in four cities of Saudi Arabia (Riyadh, Jeddah, Dammam and Mecca). It encompassed a population from various walks of life. Some problems were encountered in conducting this study: failure of some participants to attend weekly to the clinic for proctoscopic examination, either due to reticence to undergo proctoscopy or inability to attend for other reasons (e.g. difficulty with transportation). Therefore, comparison was only possible between the baseline and last visits. Although this is a prospective study, certain pitfalls are inherent. The major deficit was the lack of randomisation with lack of a suitable placebo. The investigators were not blinded and patients were not randomised so a degree of subjective bias may have occurred in the assessment. Moreover, some patients in this study may have already been using some other forms of anti-haemorrhoidal treatments, which they failed to disclose to us. Hence, the improvement in symptoms may not be entirely attributable to Daflon. Despite such deficiencies, the findings demonstrate a significant improvement in virtually all haemorrhoidal symptoms after a four-week course of treatment.

This study confirms the safety and efficacy of Daflon in the treatment of the symptoms of haemorrhoidal disease. Previous reports have confirmed the efficacy of oral diosmin (Daflon; Les Laboratoires Servier, Orleans, France), compared with placebo.^8-10 In our study the side effects were minimal and trivial and were averted by taking the tablets after meals. An advantage is Daflon’s safety in pregnancy, a period when ‘piles’ is common and surgery is a relative contraindication.¹¹ This study included three pregnant females who presented with congestive haemorrhoidal disease and responded favourably to Daflon. Also, another advantage is lack of Daflon interaction with anticoagulant drugs such as warfarin. This study included a patient who had Behcet’s disease and was on warfarin; his haemorrhoidal symptoms were controlled with a month course of Daflon, which averted surgery with all its attendant risks.

As the long-term effect of Daflon treatment was not addressed in this study, it would be sensible to have long-term follow-up for patients in this study to see if symptoms recurred and how long after the initial treatment, and the percentage of the study patients who eventually come to surgery. The author has treated recurrent symptoms with Daflon. Failure to control symptoms is an indication for other forms of treatment that are available to the surgeon. It is just over 18 months since the conclusion of the study and to the author’s best knowledge, only five of the study patients have required surgery, to date.

A new promising operation that is suitable for ‘piles’, especially that accompanied by mucosal prolapse, is stapled hemorrhoidectomy. This was first introduced by Longo in 1998 and it has been gaining popularity due to its numerous advantages in terms of short hospital stay, less pain and rapid return to work.¹² Daflon will continue to play a role in reducing post-hemorrhoidectomy bleeding even after the stapled procedure.⁶

This study confirms the value of Daflon in treating various haemorrhoidal symptoms in patients attending the surgical clinic. It also confirms its value in significantly improving the proctoscopic appearance of ‘piles’ within four weeks. This suggests that Daflon may be suitable as an initial treatment of all haemorrhoid symptoms and, in particular, before embarking on surgical management with its associated risk of morbidity.

The author is indebted to all members of the Daflon group in the participating hospitals: Professor Sulaiman Sulaiman and Dr. Saif Ismail, consultant surgeons, Security Forces Hospital, Riyadh; Dr. Faiza Fadl Elahi, consultant surgeon, King Abdul Aziz Hospital, Jeddah; Dr. Ismail Khodary, consultant surgeon, King Fahad General Hospital, Jeddah; Drs. Khaled Dhafer and Mashaal Al Harthy, consultant surgeons, Al Nour Hospital, Mecca. The author also thanks Nagy Research, Cairo, Egypt for conducting the statistical analyses in the study.

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TABLE 1. IMPROVEMENTS OF VARIOUS HAEMORRHOIDAL SYMPTOMS AT FIRST AND LAST VISITS
Symptom	Degree of severity	Number of patients		P value
		First visit (baseline)	Last visit (at four weeks)
Pain	Severe	60 (22)	3 (1)	<0.001
	Moderate	80 (30)	11 (4)
	Mild	72 (27)	45 (17)
	None	56 (21)	209 (78)
Heaviness	Severe	35 (13)	0	<0.001
	Moderate	64 (24)	8 (3)
	Mild	67 (25)	24 (9)
	None	102 (38)	236 (88)
Bleeding	Severe	24 (9)	0	<0.001
	Moderate	108 (40)	13 (5)
	Mild	88 (33)	35 (13)
	None	48 (18)	220 (82)
Pruritus	Severe	24 (9)	0	<0.001
	Moderate	64 (24)	8 (3)
	Mild	89 (33)	35 (13)
	None	91 (34)	225 (84)
Mucus discharge	Severe	19 (7)	1 (0.4)	<0.001
	Moderate	29 (11)	3 (1.1)
	Mild	86 (32)	27 (10.1)
	None	134 (50)	237 (88.4)
Values in parentheses are percentages