Elsevier

The Lancet

Volume 349, Issue 9044, 4 January 1997, Pages 11-14
The Lancet

Articles
A randomised, prospective, double-blind, placebo-controlled trial of glyceryl trinitrate ointment in treatment of anal fissure

https://doi.org/10.1016/S0140-6736(96)06090-4Get rights and content

Summary

Background

Anal fissure is most commonly treated surgically by internal anal sphincterotomy. However, there is some concern over the effects of this procedure on continence. Nitric oxide donors such as glyceryl trinitrate (GIN) have been shown to cause a reversible chemical sphincterotomy capable of healing fissures in a small series of cases. This study reports a prospective, randomised, double-blind, placebo-controlled trial to test the hypothesis that topical GIN is the best first-line treatment for chronic anal fissure.

Methods

80 consecutive patients were randomised to receive treatments with topical 0·2% GTN ointment or placebo. Maximum anal resting pressure (MARP) was measured with a constantly perfused side-hole catheter before and after the first application of trial ointment. Anodermal blood flow was measured during manometry by laser Doppler flowmetry. After initial treatments, patients were given a supply of ointment (either GTN or placebo) to be applied to the lower anal canal twice daily. Patients were reviewed 2-weekly. At the initial and follow up visits patients were asked to record pain experienced on defaecation on a linear analogue pain score. Endpoints were healing of the fissure or condition after 8 weeks of treatment.

Findings

After 8 weeks, healing was observed in 26/38 (68%) patients treated with GTN and in 3/39 (8%) patients treated with placebo (p<0·0001, χ2 test). Linear analogue pain score fell significantly in both groups after 2 weeks of treatment. This fall was maintained in those treated with GTN but pain scores returned to pre-treatment values by 4 weeks on treatment with placebo. MARP fell significantly from a mean of 115·9 (SD 31·6) to 75·9 (30·1) cm H2O (p<0·001, Student's paired t-test) in patients treated with GTN but no change was seen in MARP after placebo. Anodermal blood flow measured by laser Doppler flowmetry significantly increased after application of GTN ointment but was unaffected by placebo.

Interpretation

Topical GTN provides rapid, sustained relief of pain in patients with anal fissure. Over two-thirds of patients treated in this way avoided surgery which would otherwise have been required for healing. Long-term follow up is needed to assess the risk of recurrent fissure in patients with GTN.

Introduction

Anal fissure is characterised by pain on defaecation, rectal bleeding, and spasm of the internal anal sphincter (IAS). The aetiology of anal fissure is contentious; it may be due to ischaemia of the posterior commissure of the anal canal, exacerbated by hypertonicity of the internal anal sphincter.1, 2 Although conservative treatment with topical ointments is successful for most acute anal fissures, they do not usually help in the treatment of chronic anal fissures.3, 4, 5 Surgical treatments for fissure overcome spasm of the IAS by forcible anal dilatation or internal sphincterotomy. Both anal dilatation and sphincterotomy are associated with short-term and long-term impairment of continence in up to 30% of patients.6, 7, 8 A non-surgical method of reducing anal pressure to treat anal fissure would be useful.9 Nitric oxide (NO) has recently been shown to be an inhibitory neurotransmitter in the IAS.10 Organic nitrates are degraded by cellular metabolism releasing NO.11 Glyceryl trinitrate (GTN) ointment applied to the anus causes a fall in maximum anal resting pressure (MARP) amounting to a reversible “chemical sphincterotomy”.12 Anodermal blood flow may be inversely related to MARP because the blood supply to the mucosa comes predominantly from vessels which cross the sphincter. Increase in anodermal blood flow has been reported after lateral internal sphincterotomy and topical applications of nitrates.13, 14 Small, uncontrolled studies have suggested that GTN ointment may be an effective treatment for chronic anal fissure but no prospective randomised trial has been done.14, 15, 16, 17 We evaluated topical GTN ointment in the treatment of chronic fissure in a randomised, double blind, placebo-controlled trial.

Section snippets

Methods

Consecutive patients who attended sugical outpatients clinics at two hospitals with chronic anal fissure were recruited. All patients had had symptoms of anal fissure of more than 6 weeks with fibrosis at the base of the fissure and were therefore deemed to be chronic. Patients were randomly allocated to receive either 0·2% GTN ointment (Percutol, Dominion Pharma, Haslemere, UK) diluted 1 in 5 with white soft paraffin or placebo (white soft paraffin) in a double-blind study. Randomisation was

Results

80 consecutive patients with chronic anal fissure were recruited between June, 1995, and April, 1996. 39 patients were randomised to treatment with 0·2% GTN ointment and 41 to placebo (figure 1). One patient in each group was found not to have an anal fissure on attending for manometry and were therefore excluded. One patient randomised to placebo failed to attend despite several postal reminders. Thus 38 patients were treated with 0·2% GTN ointment and 39 patients received placebo. Ten

Discussion

This study shows that 0·2% GTN ointment applied to the lower anal canal is effective in treating over two-thirds of chronic anal fissures which would otherwise require operation. In contrast with surgical sphincterotomy, “chemical sphincterotomy” with GTN is reversible and therefore unlikely to have long-term adverse effects on continence. In common with surgical sphincterotomy, pain relief is rapid and sustained in those patients treated with GTN. An initial reduction in pain score after 2

References (21)

  • NJ Mangione et al.

    Phenomenon of nitrate tolerance

    Am Heart J

    (1994)
  • B Klosterhalfen et al.

    Topography of the inferior rectal artery: a possible cause of chronic, primary anal fissure

    Dis Colon Rectum

    (1989)
  • CP Gibbons et al.

    Anal hypertonia in fissures: cause or effect?

    Br J Surg

    (1986)
  • SL Jensen

    Treatment of first episodes of acute anal fissure: prospective randomised study of lignocaine ointment versus hydro cortisone ointment or warm sitz baths plus bran

    BMJ

    (1986)
  • MR Lock et al.

    Fissure-in-ano: the initial management and prognosis

    Br J Surg

    (1977)
  • EE Frezza et al.

    Conservative and surgical treatment in acute and chronic and fissure. A study on 308 patients

    Int J Colorectal Dis

    (1992)
  • H Abcarian

    Surgical correction of chronic anal fissure: results of lateral internal sphincterotomy vs fissurectomy-midline sphincterotomy

    Dis Colon Rectum

    (1980)
  • G Milito et al.

    Subcutaneous lateral internal sphincterotomy in the treatment of chronic anal fissure

    Italian J Surg Sci

    (1983)
  • IT Khubchandani et al.

    Sequelae of internal sphincterotomy for chronic fissure in ano

    Br J Surg

    (1989)
  • AH Sultan et al.

    Prospective study of the extent of internal anal sphincter division during lateral sphincterotomy

    Dis Colon Rectum

    (1994)
There are more references available in the full text version of this article.

Cited by (338)

  • Fissure-in-Ano

    2019, Shackelford's Surgery of the Alimentary Tract: 2 Volume Set
  • Update on the management of anal fissure

    2015, Journal de Chirurgie Viscerale
  • Proctology

    2023, Deutsche Medizinische Wochenschrift
View all citing articles on Scopus
View full text