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