Correspondence
Topical Nitroglycerin Therapy for Anal Fissures and Ulcers
N Engl J Med 1995; 333:1156-1157October 26, 1995
- Article
To the Editor:
Myenteric nerves innervating the internal sphincter muscle of the anus produce and release nitric oxide,1,2 the chemical messenger that mediates relaxation of this muscle.1 A derangement in nitric oxide regulation may underlie the anal-sphincter hypertonicity associated with anal fissures and ulcers. Nitroglycerin, which is locally metabolized to nitric oxide, lowers the mean resting pressure of the anal sphincter when applied topically to the anus.3 A pilot study of 15 patients showed that topical nitroglycerin was useful in treating anal fissures and ulcers.4
Forty patients with anal fissures (26 women and 14 men; mean age, 38 years) and 14 patients with anal ulcers (9 women and 5 men; mean age, 41 years) were recruited to participate in a trial of 0.3 percent nitroglycerin ointment, applied topically to the anus. This study was approved by the institutional review board of the Mount Sinai School of Medicine. After a diagnosis of anal fissure or ulcer was established, the patients were asked to rate their anal pain on a scale from 0 to 10, on which 0 denoted no pain and 10 severe pain. Approximately 200 mg of ointment was applied topically to the anal canal by the investigator. Five minutes later the patients were asked to rate their pain again.
The mean (±SD) pain scores before and after treatment were 4.8±2.5 and 1.4±1.4, respectively (difference, 3.4; 95 percent confidence interval, 2.7 to 4.0; P<0.001). Forty-six (90 percent) of the 51 patients able to assess their pain quantitatively had some relief with nitroglycerin. The patients were then instructed to continue nitroglycerin therapy at least four times daily and also after each bowel movement. A high-fiber diet, supplemented by psyllium seed as needed, was also suggested. The patients were questioned about their pain and reexamined every one to two weeks for eight weeks or until their lesions had healed.
Thirty patients with anal fissures and 11 patients with anal ulcers complied with the treatment regimen and completed the requested follow-up schedule. Most had relief of pain, when there was pain, for two to six hours after each application of nitroglycerin. The fissures healed in two weeks or less in 9 patients (30 percent), in four weeks or less in 21 patients (70 percent), and in eight weeks or less in 23 patients (77 percent). The ulcers healed in two weeks or less in two patients (18 percent), in four weeks or less in three patients (27 percent) and in eight weeks or less in six patients (54 percent). None of the patients became incontinent during treatment. Side effects were limited to mild, transient headaches in 12 patients, among whom 2 limited but did not discontinue their use of the ointment because of the headaches.
Nitric oxide mediates relaxation of the internal anal sphincter in vivo and in vitro. Nitroglycerin also causes relaxation of the sphincter, probably by the same mechanism. It appears that nitroglycerin provides rapid relief of anal pain and promotes the healing of anal fissures and ulcers.
4 ReferencesStephen R. Gorfine, M.D.
Mount Sinai School of Medicine, New York, NY 100291
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Loder PB ,Kamm MA ,Nicholls RJ ,Phillips RK . “Reversible chemical sphincterotomy“ by local application of glyceryl trinitrate. Br J Surg 1994;81:1386-1389
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Gorfine SR . Treatment of benign anal disease with topical nitroglycerin. Dis Colon Rectum 1995;38:453-457
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