| Abstract|| |
Aim of the study: To assess the clinical efficacy of 0.2% glyceryl trinitrate ointment in the management of acute and chronic anal fissures.
Patients and methods: A prospective clinical study conducted on consecutive patients presented to the surgical clinic of King Khalid University Hospital, Riyadh with acute and chronic anal fissures, from January to December 2003. These patients were treated with topical 0.2% glyceryl trinitrate paste in soft white paraffin three times a day. Patients were examined at regular intervals to evaluate the fissure status, adverse reactions, symptomatic control and recurrence.
Results: This study comprised 121 patients, six of them were lost to follow-up and 109 (94.7%) of the remaining 115 patients were cured. Of those cured, 13 patients (11.3%) presented with acute and 102 (88.7%) with chronic fissures. There were 98 male and 17 female patients with median age of 41 years (range, 14-70 years). Complete symptomatic relief was achieved in all patients within one month of therapy. Two patients, with chronic anal fissures presented with recurrent symptoms within one month of the completion of therapy both of them were successfully treated with repeat glyceryl trinitrate course. Treatment had to be terminated in six (5.2%) patients: five (4.3%) experienced intolerable adverse effects and one (0.8%) patient failed to respond. All these patients were successfully treated with lateral internal sphincterotomy. No patient complained of change in continence.
Conclusion: Glyceryl trinitrate ointment produces adequate symptomatic control and healing of the anal fissures and can be considered as one of the recommended treatment options
Keywords: Anal fissure, glyceryl trinitrate ointment, lateral internal sphincterotomy, nitric oxide donor.
|How to cite this article:|
El Tinay OE, Guraya SY. The use of 0.2% glyceryl trinirate oinment for anal fissures. Saudi J Gastroenterol 2005;11:40-4
Anal fissure is a benign painful condition of the anoderm. Raised resting internal anal sphincter pressure is important in the pathogenesis of anal fissure, possibly by impairing tissue perfusion and leading to ischemic ulcer ,,, . Conservative management of the anal fissures traditionally involves stool softeners, warm sitz baths and the application of topical anesthetics. Chronic fissures tend to be more resistant to conservative management characterized by frequent recurrences  . Surgical procedures to reduce resting anal tone for the recalcitrant fissures are effective but carry a significant risk of permanent minor impairment of continence , . Manual anal dilatation may cause irreversible , uncontrolled injury to the internal and external anal sphincters  with the associated incidence of fecal incontinence being 39%  . Lateral subcutaneous internal sphincterotomy leads to successful healing of the fissure in more than 90 % patients but temporary incontinence for the flatus or feces occurs in 0-30 % of the patients  . Such observations have fuelled attempts to develop non-operative measures for reducing internal sphincter spasm.
Nitric oxide has emerged as one of the most important neurotransmitter mediating internal sphincter relaxation.  Topical glyceryl trinitrate (GTN), a nitric oxide donor produces a successful chemical sphincterotomy and improves anodermal blood flow  . The aim of this study was to present a more pragmatic assessment of the ultimate usefulness of GTN in the treatment of acute and chronic anal fissures.
| Patients and Methods|| |
This prospective study included the consecutive patients with acute and chronic anal fissures presented to the Surgical Clinic of King Khalid University Hospital Riyadh, Saudi Arabia from January to December 2003. These patients had persistent, symptomatic anal fissures that were recalcitrant to sitz bath, fiber supplements and topical anesthetics. The chronicity of the fissure was established by the presence of a sentinel pile, hypertrophied papillae or exposed internal sphincter fibers at the base of the anal fissure. Fifteen patients with inflammatory bowel disease, HIV infection and those with cardiac disease using oral or sublingual nitrates were excluded from this study. Informed consent was obtained from all the patients after an explanation of the nature of the disease, treatment method and the possible unwanted effects. Patients were instructed to apply small amounts of especially prepared 0.2% GTN paste in soft white paraffin, to the anoderm with finger tips three times per day  . All patients were encouraged to take high fiber diet, warm sitz baths twice a day and warned about the possible adverse effects. Patients were evaluated at two-week intervals and at each visit the symptoms control, adverse effects and fissure status were recorded. If there was symptomatic relief or the fissure healing was in progress, the treatment was continued for a total duration of eight weeks. Afterwards, the patients were given the option to resume the treatment in case of recurrence or abandon this therapy and consider surgical intervention. Two follow up visits, at twomonth interval, were arranged after the completion of the initial therapy to establish the long-term durability of 0.2% GTN ointment. Patients were declared cured in case of complete symptomatic relief with fissure healing. The SPSS 10.0 software package (SPSS Inc., Chicago, IL) was used for data analysis.
| Results|| |
Out of 121 patients, six were lost to follow up. Of the remaining 115 patients, (98 male and 17 female patients, with a mean age of 41 years, range 14 -70) for males and 40.2 years (range 14-67) for females [Table - 1].
One hundred nine (94.7%) patients were cured of their disease with the use of 0.2% GTN ointment. Of those with complete cure, 1 ipatients (10%) had acute and 98 patients (90%) chronic fissures [Figure - 1].
Two (1.7%) patients with acute and three (2.6%) with chronic anal fissures presented with symptomatic relief sufficient to obviate the need for any operative treatment, despite the persistence of fissure. Complete symptomatic relief was obtained within one month of the therapy for all those patients cured of the disease. Two patients (1.7%) presented with recurrent symptoms three months after the initial treatment which was successfully treated with a second course of 0.2% GTN. No change in flatus or fecal continence was reported in this study. Five patients (4.3%) experienced intolerable side effects while one (0.8%) patient failed to respond to 0.2% GTN therapy [Table - 2]. All these patients were treated with lateral internal sphincterotomy without any postoperative complaint.
| Discussion|| |
The present clinical trial establishes the clinical efficacy of 0.2% GTN ointment in the treatment of anal fissures. The published data of a high cure rate of 70 80% in various studies ,, with a paucity of significant side effects are encouraging [Table - 3]. In a recent study  the recurrence rate has been less than 5% and major complications were quite uncommon with the use of GTN ointment. Gorfine used 0.3% GTN ointment four times a day to induce healing in 12 of 15 anal fissures within one month of treatment (18) A subsequent study demonstrated a 77% healing rate for anal fissure with a reported incidence of 35% for headaches  . In the present series, only five patients (4.3%) felt headache because the dose of GTN used was significantly lower than the dose used in other studies ,, Similarly, tachyphylaxis (rapid development of tolerance to the effects of GTN) was not observed in this study which is explained by the volatility of the preparation when exposed to air and the short half-life of GTN. The published literature ,, has shown a recurrence rate of 3-25% with internal sphincterotomy for anal fissures while in this study two patients (1.7%) had symptomatic recurrence GTN ointment necessitating repeat therapy. Kennedy et al  have concluded in their placebo-controlled, randomized, doubleblind trial of 43 patients that topical GTN produced a successful chemical sphincterotomy, which resulted in longterm healing of 59% of chronic anal fissures.
GTN therapy seems to offer outright benefit for those patients with the highest risk of anal incontinence, including multiparous women, and those with previous anal surgery, recurrent fissures or peri anal irradiation  . Cost effectiveness and complete treatment in the Outpatient Clinic, with a subsequent reduction in the hospital waiting lists are among other advantages of this treatment modality. The reported efficacy of nitric oxide donors varies widely in the literature (47-88%) , , depending on the agent used, the duration of treatment, whether the fissure was acute or chronic, and how the success of therapy was measured i.e. symptomatic relief, healed fissure or manometric finding of reduced anal sphincter tone. This highlights the need for further data-based clinical trials to elucidate the correct dose, optimal dosing intervals and the best delivery method of GTN.
Lateral internal sphincterotomy has been among the most gratifying surgical interventions for anal fissures  but published literature has reported a 2.3 wound infection rate  and 0 to 34 incidence of incontinence to flatus and liquid stool  following this procedure In the present study, no change in the continent status was reported with the application of GTN, an observation which elaborates the safe clinical profile of the GTN therapy.
In conclusion, GTN is a useful therapeutic modality in the management of acute and chronic anal fissures, which are refractory to dietary modifications, fiber supplements and sitz baths. As GTN is safe and effective we suggest to perform a randomized comparative study with surgical gold standard treatment.
| References|| |
|1.||Gibbons CP, Read NW. Anal hypertonia in fissure: cause or effect? Br J Surg 1986; 73: 443-5. [PUBMED] |
|2.||McNamara MJ, Percy JP, Fielding IR. A manometric study of anal fissure treated by subcutaneous lateral sphincterotomy. Ann Surg 1990; 211: 235-8. [PUBMED] [FULLTEXT]|
|3.||Schouten WR, Briel JW, Auwerda JJA. Relationship between anal pressure and anodermal blood flow: the vascular pathogenesis of anal fissure. Gut 1993; 34: S25. |
|4.||Golligher J. Surgery of the anus, rectum and colon. London: Balliere Tindall 1984; 170: 170-91. |
|5.||Oh C, Divino CM, Steinhagen RM. Anal fissure: 20- year experience. Dis Colon Rectum 1995; 38: 378-82. [PUBMED] |
|6.||Snooks S, Henry MM, Swash M. Fecal incontinence after anal dilatation. Br J Surg 1984; 71: 617-8. [PUBMED] |
|7.||Khubchandani IT, Reed JF. Sequel of internal sphincterotomy for chronic fissure in ano. Br J Surg 1989; 76: 431-4. [PUBMED] |
|8.||Farouk R, Bartolo DCC. The use of endoluminal ultrasound in the assessment of patients with fecal incontinence. J R Coll Edinb 1994; 39: 312-18. |
|9.||MacDonald A, Smith A, McNeill AD, Finlay IG. Manual dilatation of the anus. Br J Surg 1992; 79: 1381-2. |
|10.||Pernikoff BJ, Eisenstat TE, Rubin RJ, Oliver GC, Salvati EP. Reappraisal of partial lateral internal sphincterotomy. Dis Colon Rectum 1994; 37: 1291-95. [PUBMED] |
|11.||Ward DI, Miller BJ, Schache DJ, Cohen JR. Cut or paste? The use of glyceryl trinitrate in the treatment of acute and chronic anal fissure. Aust NZ J Surg 2000; 70: 19-21. |
|12.||Watson SJ, Kamm MA, Nicholls RJ, Phillips RK. Topical glyceryl trinitrate in the treatment of chronic anal fissure. Br J Surg 1996; 83: 771-5. [PUBMED] |
|13.||Evans J, Luck A, Hewett P. Glyceryl trinitrate vs lateral sphincterotomy for chronic anal fissure. Dis Colon Rectum 2001; 44: 93-7. [PUBMED] |
|14.||Hyman NH, Cataldo PA. Nitroglycerine ointment for anal fissures: effective treatment or just a headache? Dis Colon Rectum 1999; 42: 383-5. [PUBMED] |
|15.||Bacher H, Mischinger HJ, Werkgartner G. Local nitroglycerine for treatment of anal fissures: an alternative to lateral sphincterotomy. Dis Colon Rectum 1997; 40:840-5. |
|16.||Lund JN, Scholefield JH. A randomized, prospective, double-blind, placebo- controlled trial of glyceryl trinitrate ointment in the treatment of anal fissure. Lancet 1997; 349: 11-14. [PUBMED] [FULLTEXT]|
|17.||The Standard Task Force, American Society of Colon and Rectal Surgeons, Rosen L, Abel ME Gordon PH. Practice Parameters for The Management of anal fissure. Dis Colon Rectum 1992; 35: 206-8. |
|18.||Gorfme SR. Treatment of benign anal disease with topical nitroglycerine. Dis Colon Rectum 1995; 38: 453-7. |
|19.||Gorfine SR. Topical nitroglycerine therapy for anal fissures and ulcers. N Engl J Med 1995; 333 156 - 7. |
|20.||Richard CS, Gregorie R, Plewes EA, Silverman R. Internal sphincterotomy is superior to topical nitroglycerine in the treatment of chronic anal fissure. Results of randomized, controlled trial by the Canadian Colorectal Surgical Trial Group. Dis Colon Rectum 2000; 43: 1048-1055. |
|21.||Notoras MJ. Anal fissure and stenosis. Surg Clin. North Am. 1988; 68: 1427-40. |
|22.||Keighley MRB, Greca F, Nevah E, Hares M, Alexander- Williams J. Treatment of anal fissure by lateral sphincterotomy should be under general anesthesia. Br J Suirg 1981; 68: 400-1. |
|23.||Kennedy ML, Sowter S, Nguyen H, Lubowski DZ. Glyceryl trinitrate ointment for the treatment of chronic anal fissure. Results of a placebo- controlled trial and long-term follow-up. Dis Colon Rectum 1999; 42: 10006. |
|24.||Schouten WR, Briel JW, Boerma MD, Auwerda JJ, Wilms EB, Graatsma BH. Pathophysiologal aspects and clinical outcome of intra-anal application of isosorbide dinitrate in patients with chronic anal fissure. Gut 1996; 39: 465-9. |
|25.||Rattan S, Sarkar A, Chakder S. Nitric oxide pathway in recto-anal inhibitory reflex of opossum internal anal sphincter. Gastroenterology 1992; 103: 43-50. [PUBMED] |
|26.||Gracia-Aguilar J, Belmonte C, Wong WD, Lowry AC, Madoff RD. Open vs closed sphincterotomy for chronic anal fissure: long term results. Dis Colon Rectum 1996; 39: 4403. |
|27.||Lewis TH, Corman ML, Prager ED, Robertson WG. Long term results of open and closed sphincterotomy for anal fissure. Dis Colon Rectum 1988; 31: 368-71. [PUBMED] |
|28.||Arnell TD, Stamos MJ. Sphincterotomy for anal fissure. Semin colon rectal surg 1997; 8: 24-8. |
Omer El Farouq El Tinay
Department of Surgery, King Khalid University Hospital, P 0 Box 7805. Riyadh 11472
Source of Support: None, Conflict of Interest: None
[Figure - 1]
[Table - 1], [Table - 2], [Table - 3]