Nitroglycerin in theTreatment of Anal Fissure

Source: Lund JN, Scholefield JH. Lancet 1997;349:11-14.

At one point, all primary care clinicians are presented with patients who have pain with defecation, rectal bleeding or blood on the toilet tissue, and spasm of the internal anal sphincter (IAS). This triad is usually a result of an anal fissure. Topical ointment treatment is usually sufficient therapy. It is unknown how many hemorrhoids being treated in this way are actually anal fissures. Occasionally, patients don't get better, and further investigation provides evidence for anal fissure. Surgical dilatation and sphincterotomy have been the only treatments for this, but the problem of a short- or long-term impairment of continence in one-third of the patients prevents most patients from undergoing surgery. They learn to live with it.

Nitric oxide (NO) has been found to be efficacious in many areas of the body. Not surprisingly, in the anal sphincter, NO has been found to be an inhibitory neurotransmitter of the internal anal sphincter. Nitroglycerin or glyceryl trinitrate ointment degrades by cellular metabolism and releases nitric oxide. It has been found to drop maximum anal resting pressure. This would be equivalent to a chemical "sphincterotomy."

Lund and Scholefield have taken 80 consecutive patients with anal fissure and randomized them to identical-looking creams, one of which was placebo, the other of which was 0.2% GTN ointment. By measuring the maximum anal resting pressure and doing manometry over time, the patients were then given either medication or placebo in a double-blind fashion and told to apply this twice a day while recording their pain as an objective end point. After eight weeks, the data were collected. It was found that healing had occurred in 26 of the 38 (68%) patients treated with the nitroglycerin ointment. Only 8% of the patients treated with placebo had gotten better. The biggest side effect was headache, which in most patients was well-tolerated and caused discontinuation of the drug in only one patient.

By doing maximum anal resting pressures and manometry, they were able to find a drop in these pressures and a rise in anodermal blood flow.

Nitroglycerin ointment seems to be a viable treatment alternative to surgery of anal fissures.

Comment by Len Scarpinato, DO

The efficacy of nitroglycerin in conditions other than coronary ischemia has been known for many years. There has been at least one reported case of using topical nitrates in ischemic limbs.

However, to look at its effect in anal fissure is nothing but revolutionary. For primary care clinicians who see a fair amount of hemorrhoids, and probably anal fissures, treatment is exasperating, especially after the normal steroid enema and local analgesics do not work. Once an anal fissure is suspected or discovered, the only option has been surgery. With the high rate of incontinence and discomfort caused by this procedures, it's no surprise that patients refuse.

Now there's a potential therapy. Acting on several anecdotal reports in the literature that anal fissures can be healed by topical nitroglycerin, Lund and Scholefield completed a prospective, randomized, double-blind, placebo-controlled trial. It has shown that topical GTN is an effective therapy compared to placebo in the treatment of chronic anal fissure. By performing effective manometry, studies have also given us an idea about how it works.

There is still some question, however; the issue of tachyphylaxis that occurs in the angina patient has not been explored. The headache issue is real, but only one of their patients stopped treatment due to it. It is still not clear as to how long one should medicate a treatment failure before sending the patient to surgery.

In any case, the authors have contributed to the literature on anal fissures in a significant way.

Dr. Scarpinato is Associate Professor, Medical College of Wisconsin; Critical Care Curriculum Coordinator, St. Mary's Hospital, Milwaukee.