A randomized trial of oral vs. topical diltiazem for chronic anal fissures. Double blind randomised controlled trial of topical glyceryl trinitrate in anal fissure. A comparison of the effects of diltiazem and glyceryl trinitrate ointment in the treatment of chronic anal fissure: a randomized clinical trial. A dose finding study with 0.1%, 0.2%, and 0.4% glyceryl trinitrate ointment in patients with chronic anal fissures. A prospective, randomized, double-blind, placebo-controlled trial of glyceryl-trinitrate ointment in the treatment of children with anal fissure. The use of glyceryl trinitrate (GTN) in the treatment of chronic anal fissure in children. Topical anal fissure treatment: placebo-controlled study of mononitrate and trinitrate therapies. Randomized clinical trial of botulinum toxin plus glyceryl trinitrate vs. botulinum toxin alone for medically resistant chronic anal fissure: overall poor healing rates. A prospective randomized trial of diltiazem and glyceryltrinitrate ointment in the treatment of chronic anal fissure.
Chemical sphincterotomy has proved effective in treating chronic anal fissure. Glyceryl trinitrate is the most widely used agent, and topical 0.2 percent glyceryl trinitrate ointment heals up to two thirds of chronic anal fissures. Unfortunately, however, many patients experience troublesome headaches as a side effect of this treatment. This study assessed the effectiveness of oral and topical diltiazem in healing chronic fissures.
                Fifty consecutive patients with chronic anal fissures were randomly assigned to receive oral (60 mg) or topical (2 percent gel) diltiazem twice daily for up to eight weeks. Anal manometry was performed before and after the first dose, and blood pressure was recorded at 15-minute intervals. Patients were reviewed fortnightly, pain was expressed with a visual linear analog scale, blood pressure was recorded, fissure healing was assessed, and side effects were noted.
                Twenty-four patients received oral diltiazem, and 26 received topical diltiazem. Mean (+/- standard error of the mean) maximum resting anal pressures fell by 15 and 23 percent from 95 +/- 4 to 81 +/- 4 and from 102 +/- 5 to 79 +/- 5 cm H2O in the two groups, respectively. There was no significant reduction in blood pressure during the study or at follow-up in either group. Fissure healing was complete in 9 patients (38 percent) receiving oral diltiazem and 15 (65 percent) on topical treatment by eight weeks. Oral diltiazem caused side effects in eight patients (rash, two; headaches, two; nausea or vomiting, three; reduced smell and taste, one), whereas no side effects were seen in those receiving topical therapy (P = 0.001).
                Oral and topical diltiazem heal chronic anal fissures. Topical diltiazem is more effective, achieving healing rates comparable to those reported with topical nitrates, with significantly fewer side effects. To determine the effectiveness and safety of topical glyceryl trinitrate (GTN) in the management of acute anal fissure in children.
                Individual children were randomised to receive GTN paste or placebo for six weeks in addition to oral senna and lactulose. Patients took laxatives alone for a further 10 weeks. Each week a research nurse telephoned families to assess pain scores and give advice. Main outcome measures were validated standardised pain scores and time to painless defaecation.
                Forty subjects were recruited from 46 eligible children; 31 children completed the trial (13 in the GTN group and 18 in the placebo group). No differences in the proportion of those achieving pain free defaecation with relation to time were seen between the two groups. Similarly, there were no significant differences in pain scores between the two groups over the 16 week study period. However, in both groups pain scores had decreased significantly. There were no differences in the incidence of rectal bleeding, faecal soiling, presence of visible fissure, skin tag, or faecal loading at outpatient review at the time of recruitment, or at 6 weeks and 16 weeks. No serious adverse effects were observed.
                This study suggests that 0.2% GTN paste is ineffective in the treatment of acute anal fissures in childhood. However the overall fissure healing rate is high (84%) with associated reduction in pain scores, suggesting that a nurse based treatment programme can achieve a high rate of fissure healing. Anal fissure is a common problem affecting all age groups with an equal incidence in both sexes. Traditional surgical treatments, like manual anal dilatation or a sphincterotomy, effectively heal most fissures within a few weeks but such procedures may result in anal incontinence. In recent years, various medical therapies have been used for the treatment of chronic anal fissure without fear of incontinence.
                Ninety patients with a symptomatic anal fissure were randomly divided into three groups. Group I was treated with 2% diltiazem ointment, Group II was treated with 0.2% glyceryl trinitrate (GTN) ointment, and Group III was kept as the control group. The improvement in the signs and symptoms, the time taken for healing, and side effects were recorded in each group. The patients were followed up monthly and then every 3 months for any recurrence of fissure. Comparative evaluations of the three groups regarding an improvement in symptoms, progress in healing, appearance of side effects, and recurrence were made using the Tukey HSD test.
                Diltiazem ointment was found to be superior regarding pain relief, fewer side effects, and late recurrence as compared with GTN ointment.
                Diltiazem ointment (2%) and GTN ointment (0.2%) are both effective treatment modalities for chronic anal fissure, with diltiazem giving better patient outcome. Anal fissure is a common painful condition affecting the anal canal. The majority of acute fissures heal spontaneously. However, some of these acute fissures do not resolve but become chronic. Chronic anal fissures were traditionally treated by anal dilation or by lateral sphincterotomy. However, both of these surgical treatments may cause a degree of incontinence in up to 30% of patients. Several recent trials have shown that nitric oxide donors such as glyceryl trinitrate (GTN) can reduce sphincter pressure and heal up to 70% of chronic fissures.
                This study addressed the dose-response to three different concentrations of GTN ointment compared with placebo in a double blind randomised controlled trial.
                A double blind, multicentre, randomised controlled trial was set up to compare placebo ointment against three active treatment arms (0.1%, 0.2%, and 0.4% GTN ointment applied at a dose of 220 mg twice daily) in chronic anal fissures. The primary end point was complete healing of the fissure.
                Two hundred patients were recruited over an eight month period from 18 centres. After eight weeks of treatment the healing rate in the placebo group was 37.5% compared with 46.9% for 0.1%, 40.4% for 0.2%, and 54.1% for 0.4% GTN. None was significantly better than the placebo response. A secondary analysis excluded fissures without secondary criteria for chronicity. Healing rates were then found to be 24% in the placebo group compared with 50% in the 0.1% GTN group, 36% in the 0.2% group, and 57% in the 0.4% GTN group. These values were statistically significantly different for the placebo group compared with 0.1% GTN, 0.4% GTN, and for the GTN treated group as a whole.
                The results of this study have demonstrated the significant benefit of topical GTN when applied to patients suffering from chronic anal fissures but acute fissures showed a tendency to resolve spontaneously. The high proportion of fissures which healed in the placebo group suggests that the definition of "chronicity" needs to be reassessed. Further studies are required to confirm the optimal therapeutic strategy. Anal fissure in children usually is treated by sitz baths, stool softeners, and analgesic ointments. However, some cases are intractable to the treatment. In recent years, it has been reported that nitric oxide donors such as local glyceryl-trinitrate (GTN) ointment causes a reversible chemical sphincterotomy. Although the GTN ointment can be an alternative therapy for adult cases, it has not yet been studied in the children who suffer from anal fissure.
                Sixty-five children with anal fissure were divided randomly into 3 groups. Each group received double-blinded a topical ointment that contained either 0.2% GTN, 10% lidocaine, or placebo. These ointments were applied to the lowest part of the anal canal twice daily. Patients were periodically reviewed, and the study was ended after 8 weeks.
                Complete healing of the fissure occurred in 26 of 31 (83.9%) patients treated with GTN, 7 of 14 (50%) patients treated with lidocaine, and 6 of 17 (35.2%) treated with placebo. In 29 of 31 (93.5%) GTN-treated patients, a total relief of symptoms was observed, whereas this occurred in 7 of 14 (50%) treated with lidocaine and 6 of 11 (35.3%) in the placebo group. The differences between the study group and control groups were highly statistically significant (P < .001).
                The majority of children suffering from anal fissure will be cured and have relief of symptoms after topical application of GTN ointment to the anal canal. 0.2 per cent topical glyceryl trinitrate (GTN) ointment heals up to two-thirds of chronic anal fissures in adults although many patients experience troublesome headaches. This double blind randomised pilot study assessed the efficacy and side effects of 0.1 and 0.05 per cent GTN ointment in treatment of chronic anal fissures in children.
                15 consecutive children with chronic anal fissures were randomised to receive either 0.05 or 0.1 per cent GTN ointment applied topically twice daily for eight weeks. Clinical review was undertaken at weeks 4 and 8 and questions relating to symptoms and the incidence of headache were asked.
                The median age of the 15 (8 male) patients was 6 years (range 3-13). There were 5 anterior and 10 posterior fissures. The median duration of symptoms was 9 (3-30) months. 13/15 (86.7%) patients were taking laxatives at the time of referral. Fissure healing was complete at 8 weeks in all seven patients who received 0.05% and in 5/8 (62.5%) patients using the 0.1% ointment (Fisher's exact test, not significant). One patient from each arm experienced headaches during the first week of the trial which resolved without treatment and did not affect compliance. There were no other side effects.
                Topical glyceryl trinitrate ointment is effective in healing chronic anal fissures in children. Healing rates and side effect profile are comparable when either 0.05 or 0.1 per cent ointment is used. The present study aims to evaluate and compare the efficacy of two nitrate gels, containing isosorbide-5-mononitrate (ISMN) or glyceryl trinitrate (GTN), in the therapy of chronic anal fissure.
                The patients were randomly assigned to three groups: 0.1% ISMN gel (21 patients), 0.1% GTN gel (21 patients) and a placebo group (ten patients). The ethic committee of our hospital approved the protocol and informed consent was obtained from all participants. All patients underwent clinical examination, visual inspection of the fissure and anal manometry prior to and after therapy.
                The chronic anal fissure was completely healed in 71% of the patients treated with ISMN, 67% with GTN and in 30% from the placebo group. One patient in the ISMN group reported mild headache. Three patients in the GTN group had anal burning.
                Both topical nitrate treatments (ISMN and GTN) were effective for chronic anal fissures. The reduction of the anal pressure was slightly higher after ISMN treatment (28%) than the treatment with GTN (23%). However, the statistical difference was not significant (p>0.05). This study was designed to assess whether addition of glyceryl trinitrate to botulinum toxin improves the healing rate of glyceryl trinitrate-resistant fissures over that achieved with botulinum toxin alone.
                Patients were randomized between botulinum toxin plus glyceryl trinitrate (Group A) and botulinum toxin plus placebo paste (Group B). Patients were seen at baseline, four and eight weeks, and six months. The primary end point was fissure healing at eight weeks. Secondary end points were symptomatic relief, need for surgery, side effects, and reduction in maximum resting and squeeze pressures.
                Thirty patients were randomized. Two-thirds of patients had maximum anal resting pressures below or within the normal range at entry to the study. Healing rates in both treatment groups were disappointing. There was a nonsignificant trend to better outcomes in Group A compared with Group B in terms of fissure healing (47 vs. 27 percent), symptomatic improvement (87 vs. 67 percent), and resort to surgery (27 vs. 47 percent).
                There is some evidence to suggest that combining glyceryl trinitrate with botulinum toxin is superior to the use of botulinum toxin alone for glyceryl trinitrate-resistant anal fissure. The poor healing rate may reflect the fact that many of the patients did not have significant anal spasm at trial entry. The aim of this study was to compare prospectively diltiazem with GTN ointment in the treatment of anal fissure.
                Of 43 outpatients with chronic anal fissure, 22 patients were randomized to topical diltiazem (2%) ointment and 21 patients to glyceryltrinitrate (GTN) (0.5%) ointment twice daily for 8 weeks. During the course of treatment each patient was seen three times. Side-effects and healing were recorded.
                Healing occurred in 19 of 22 patients treated with diltiazem and 18 of 21 patients were cured with GTN (P = 0.95). Those who were treated with nitroglycerin ointment developed headache and dizziness developed after GTN in 33.3% of cases while no patient had any side-effects after diltiazem.
                Diltiazem and glyceryltrinitrate (GTN) were equally effective in healing anal fissure but the former resulted in fewer side-effects.
Medical therapy for chronic anal fissure, currently consisting of topical glyceryl trinitrate, botulinum toxin injection or the topical calcium channel blockers nifedipine or diltiazem in acute and chronic fissure and fissure in children may be applied with a chance of cure that is marginally better than placebo. For chronic fissure in adults all medical therapies are far less effective than surgery. A few of the newer agents investigated show promise based only upon single studies (clove oil, sildenifil and a "healer cream") but lack comparison to more established medications.