Treatment of Chronic Anal Fissure by Application of l-Arginine Gel: A Phase II Study in 15 Patients

Abstract

PURPOSE: Local application of exogenous nitric oxide donors, such as isosorbide dinitrate and glyceryl trinitrate, promotes fissure healing by reducing anal resting pressure and improving anodermal blood flow. The major drawback of these nitric oxide donors is headache. The overall incidence of this side effect is approximately 40 percent. Recently we have shown in healthy volunteers that L-arginine, being an intrinsic precursor of nitric oxide, reduces anal resting pressure without headache as a side effect. The aim of the present study was to evaluate the effect of L-arginine on anal resting pressure, anodermal blood flow, and fissure healing in patients with chronic anal fissure. METHODS: Fifteen patients with a chronic anal fissure were included in the present study. Before entering the study 10 patients were unsuccessfully treated by local application of isosorbide dinitrate. Six of these patients experienced severe headache during treatment with isosorbide dinitrate. All patients were treated for at least 12 weeks by local application of a gel containing L-arginine 400 mg/ml five times a day. In patients with a persistent fissure, treatment was continued until 18 weeks. Anal manometry and laser Doppler flowmetry of the anoderm were performed before treatment, 20 minutes after local application of the first dose, and after 12 weeks of treatment. A visual analog scale was used to assess fissurerelated pain and headache. RESULTS: One patient dropped out after one day of treatment, and one was excluded because of violation of the study protocol. After 12 weeks of treatment complete fissure healing was observed in 3 of 13 (23 percent) patients, and after 18 weeks the healing rate was 8 of 13 (62 percent) patients. None of the 13 patients experienced typical nitric oxide-induced headache. The pressure recordings showed a significant reduction of maximum anal resting pressure (mean ± SD): pretreatment 89 ± 17 mmHg; 20 minutes after application of the first dose 67 ± 17 mmHg; 12 weeks after treatment 74 ± 14 mmHg (P < 0.005). Recordings of anodermal blood flow showed a significant increase in flow: pretreatment 0.36 ± 0.25 volts; 20 minutes after application of the first dose 0.59 ± 0.27; 12 weeks after treatment 0.64 ± 0.33 (P < 0.005). CONCLU-SIONS: Local application of L-arginine promotes fissure healing without headache as a side effect, and L-arginine is effective even in patients not responding to isosorbide dinitrate treatment. [

A review of chronic anal fissure management

“…One small trial demonstrated promotion of anal fissure healing when L-arginine was applied topically (62% of 15 patients at 18 weeks) [160], but no effect on resting anal pressure was observed with oral preparations [161]. One benefit of this treatment, compared to NO donors (e.g.…”

Nifedipine Gel with Lidocaine in the Treatment of Anal Fissure in Children: A Pilot Study and Review of the Literature

“…Patient non-compliance and tachyphylaxis are also major drawnbacks to this treatment. Local application of another precursor of nitric oxide, L-arginine, has been reported as effective in promoting fissure healing without headache as a side effect (Gosselink et al, 2005).…”

Arginine Is a Critical Substrate for the Pathogenesis ofPseudomonas aeruginosain Burn Wound Infections

“…2A). These concentrations fall within the range of l -Arg that have been administered topically to patients (26, 27). P. aeruginosa exhibited a small, but significant, increase in swimming motility when the medium was supplemented with 100 mM l -Arg; however, at higher concentrations, swimming motility was significantly reduced (Fig.…”

“…To test this, we inoculated burned mice with P. aeruginosa cells mixed with either phosphate-buffered saline (PBS) or 0.125 g/ml l -Arg. This concentration of arginine equates to approximately 600 mM l -Arg HCl in each bolus injection or 1 g/kg of body weight per mouse and was previously shown to be safe for topical application in both rodents and humans (26, 31). In control mice (PBS treated), P. aeruginosa colonized and spread rapidly through the burn wound from the inoculation site to the perimeter of the wound by 18 h postburn and postinfection (Fig.…”