Non surgical therapy for anal fissure

Abstract

Background: Because of the disability associated with surgery for anal fissure and the risk of incontinence, medical alternatives for surgery have been sought. Most recently, pharmacologic methods that relax the anal smooth muscle, to accomplish reversibly what occurs in surgery, have been used to obtain fissure healing.

Objectives: To assess the efficacy and morbidity of various medical therapies for anal fissure.

Search methods: Search terms include "anal fissure randomized". Timing from 1966 to August 2010. Further details of the search below.

Selection criteria: Studies in which participants were randomized to a non-surgical therapy for anal fissure. Comparison groups may include an operative procedure, an alternate medical therapy or placebo. Chronic fissure, acute fissure and fissure in children are included in the review. Atypical fissures associated with inflammatory bowel disease or cancer or anal infection are excluded.

Data collection and analysis: Data were abstracted from published reports and meeting abstracts, assessing method of randomization, blinding, "intention to treat" and drop-outs, therapies, supportive measures (applied to both groups), dosing and frequency and cross-overs. Dichotomous outcome measures included Non-healing of the fissure (a combination of persistence and recurrence), and Adverse events (including incontinence, headache, infection, anaphylaxis). Continuous outcome measures included measures of pain relief and anorectal manometry.

Main results: In this update 23 studies including 1236 participants is added to the 54 studies and 3904 participants in the 2008 publication, however 2 studies were from the last version reclassified as un included, so the final number of participants is 5031.49 different comparisons of the ability of medical therapies to heal anal fissure have been reported in 75 RCTs. Seventeen agents were used (nitroglycerin ointment (GTN), isosorbide mono & dinitrate, Botulinum toxin (Botox), diltiazem, nifedipine (Calcium channel blockers or CCBs), hydrocortisone, lignocaine, bran, minoxidil, indoramin, clove oil, L-arginine, sitz baths, sildenafil, "healer cream" and placebo) as well as Sitz baths, anal dilators and surgical sphincterotomy. GTN was found to be marginally but significantly better than placebo in healing anal fissure (48.9% vs. 35.5%, p < 0.0009), but late recurrence of fissure was common, in the range of 50% of those initially cured. Botox and CCBs were equivalent to GTN in efficacy with fewer adverse events. No medical therapy came close to the efficacy of surgical sphincterotomy, though none of the medical therapies in these RCTs were associated with the risk of incontinence.

Authors' conclusions: 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.

Conflict of interest statement

none

Figures

1

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

3

Funnel plot of comparison: 1 GTN versus Placebo, outcome: 1.1 NON ‐ Healing of fissure (persistence or recurrence).

4

Funnel plot of comparison: 16 Any Surgery vs any Medical Therapy, outcome: 16.1 NON ‐ Healing (persistence or recurrence).

1.1. Analysis

Comparison 1 GTN versus Placebo, Outcome 1 NON ‐ Healing of fissure (persistence or recurrence).

1.2. Analysis

Comparison 1 GTN versus Placebo, Outcome 2 Headache.

2.1. Analysis

Comparison 2 GTN or IDN versus sphincterotomy, Outcome 1 NON ‐ Healing of Fissure (persistence or recurrence_.

2.2. Analysis

Comparison 2 GTN or IDN versus sphincterotomy, Outcome 2 Minor Incontinence.

2.3. Analysis

Comparison 2 GTN or IDN versus sphincterotomy, Outcome 3 Headache.

3.1. Analysis

Comparison 3 GTN or IDN versus Botox, Outcome 1 NON ‐ Healing.

3.2. Analysis

Comparison 3 GTN or IDN versus Botox, Outcome 2 Headache.

3.3. Analysis

Comparison 3 GTN or IDN versus Botox, Outcome 3 Minor Incontinence.

4.1. Analysis

Comparison 4 GTN versus Calcium Channel Blocker, Outcome 1 NON ‐ Healing.

4.2. Analysis

Comparison 4 GTN versus Calcium Channel Blocker, Outcome 2 Adverse Events.

4.3. Analysis

Comparison 4 GTN versus Calcium Channel Blocker, Outcome 3 Headache.

5.1. Analysis

Comparison 5 GTN versus Patch GTN, Outcome 1 NON ‐ Healing.

5.2. Analysis

Comparison 5 GTN versus Patch GTN, Outcome 2 Headache.

6.1. Analysis

Comparison 6 Dilator & Normal Care versus Normal Care Alone for acute and chronic fissure, Outcome 1 NON ‐ Healing in acute and ?chronic? fissure.

7.1. Analysis

Comparison 7 Botox versus Placebo (or Lignocaine (Colak)), Outcome 1 Non‐healing of Fissure.

7.2. Analysis

Comparison 7 Botox versus Placebo (or Lignocaine (Colak)), Outcome 2 Adverse Events.

8.1. Analysis

Comparison 8 Botox versus sphincterotomy, Outcome 1 NON ‐ Healing of the fissure.

8.2. Analysis

Comparison 8 Botox versus sphincterotomy, Outcome 2 Minor Incontinence.

9.1. Analysis

Comparison 9 Botox dose levels: High versus Higher, Outcome 1 NON ‐ Healing.

10.1. Analysis

Comparison 10 Topical CCB (0.3% topical Nifedipine) versus Hydrocortisone (both got Lignocaine), Outcome 1 NON ‐ Healing (persistence and recurrence).

11.1. Analysis

Comparison 11 Diltiazem Oral versus Topical, Outcome 1 NON ‐ Healing (persistence & recurrence).

11.3. Analysis

Comparison 11 Diltiazem Oral versus Topical, Outcome 3 Adverse Events.

12.1. Analysis

Comparison 12 GTN vs. Placebo in children, Outcome 1 NON ‐ Healing.

13.1. Analysis

Comparison 13 GTN vs placebo in adults, Outcome 1 NON ‐ Healing.

14.1. Analysis

Comparison 14 GTN vs. Lignocaine, Outcome 1 NON ‐ Healing.

14.2. Analysis

Comparison 14 GTN vs. Lignocaine, Outcome 2 Adverse Events.

15.1. Analysis

Comparison 15 CCB (Topical Nifedipine) vs. lignocaine + HC gel, Outcome 1 NON ‐ Healing.

16.1. Analysis

Comparison 16 Any Surgery vs any Medical Therapy, Outcome 1 NON ‐ Healing (persistence or recurrence).

17.1. Analysis

Comparison 17 Lignocaine ointment vs. placebo in children, Outcome 1 NON ‐ Healing.

18.1. Analysis

Comparison 18 bran vs placebo, Outcome 1 Acute Fissure Recurrence; a prophylaxis study.

19.1. Analysis

Comparison 19 lignocaine vs bran, Outcome 1 NON ‐ Healing.

20.1. Analysis

Comparison 20 lignocaine vs hydrocortisone, Outcome 1 NON ‐ Healing.

21.1. Analysis

Comparison 21 bran vs hydrocortisone, Outcome 1 NON ‐ Healing.

22.1. Analysis

Comparison 22 Sensitivity analyses, Outcome 1 Sensitivity analysis: Excluding GTN/Placebo RCTs with very low placebo response rates (

22.2. Analysis

Comparison 22 Sensitivity analyses, Outcome 2 Excluding RCT in Children with very low Placebo response rate: NON‐healing.

22.3. Analysis

Comparison 22 Sensitivity analyses, Outcome 3 Excluding RCT in Adults with very low Placebo response rate: NON‐healing.

22.4. Analysis

Comparison 22 Sensitivity analyses, Outcome 4 Excluding RCT with very low Placebo response rate: NON‐healing; Lignocaine.

22.5. Analysis

Comparison 22 Sensitivity analyses, Outcome 5 Excluding study with

22.6. Analysis

Comparison 22 Sensitivity analyses, Outcome 6 Excluding Mishra to investigate heterogeneity, Comparison 16; Medicine vs. Surgery.

22.7. Analysis

Comparison 22 Sensitivity analyses, Outcome 7 Three Largest GTN/Placebo Studies.

23.1. Analysis

Comparison 23 Botox versus Botox Dysport, Outcome 1 Non‐healing of fissure.

24.1. Analysis

Comparison 24 CCB versus LIS, Outcome 1 Non‐Healing of the Fissure.

24.2. Analysis

Comparison 24 CCB versus LIS, Outcome 2 Incontinence.

24.3. Analysis

Comparison 24 CCB versus LIS, Outcome 3 Headache.

25.1. Analysis

Comparison 25 Minoxidil versus Lidocaine, Outcome 1 Non‐healing of the fissure.

26.1. Analysis

Comparison 26 Indoramine versus placebo, Outcome 1 Non‐healing of the fissure.

26.2. Analysis

Comparison 26 Indoramine versus placebo, Outcome 2 Headache.

27.1. Analysis

Comparison 27 GTN Dose Comparisons, Outcome 1 Non‐healing of the fissure.

28.1. Analysis

Comparison 28 Calcium Channel blocker (oral Nifedipine) versus Botox, Outcome 1 Non healing of the fissure.

29.1. Analysis

Comparison 29 Long Term Follow‐up (> 1 year) ; Any Operation vs. Any Medical Therapy, Outcome 1 Non‐healing of the fissure.

30.1. Analysis

Comparison 30 GTN vs. Patient Self Dilation (vs. both), Outcome 1 Non Healing.

30.2. Analysis

Comparison 30 GTN vs. Patient Self Dilation (vs. both), Outcome 2 Headache.

31.1. Analysis

Comparison 31 Lignocaine vs Clove Oil, Outcome 1 NON ‐ Healing.

32.1. Analysis

Comparison 32 L‐Arginine vs Surgery, Outcome 1 NON ‐ Healing.

32.2. Analysis

Comparison 32 L‐Arginine vs Surgery, Outcome 2 Headache.

33.1. Analysis

Comparison 33 Sitz Baths vs Control, Outcome 1 NON ‐ Healing.

34.1. Analysis

Comparison 34 Sildenafil versus Placebo, Outcome 1 NON ‐ Healing.

35.1. Analysis

Comparison 35 Nitroglycerine Topical vs Intra‐anal injection, Outcome 1 NON ‐ Healing.

35.2. Analysis

Comparison 35 Nitroglycerine Topical vs Intra‐anal injection, Outcome 2 Headache.

36.1. Analysis

Comparison 36 diltiazem vs. no treatment, Outcome 1 NON ‐ Healing.

37.1. Analysis

Comparison 37 GTN vs ISMN, Outcome 1 NON ‐ Healing.

37.2. Analysis

Comparison 37 GTN vs ISMN, Outcome 2 Headache.

38.1. Analysis

Comparison 38 ISMN vs Placebo, Outcome 1 NON ‐ Healing.

38.2. Analysis

Comparison 38 ISMN vs Placebo, Outcome 2 Headache.

39.1. Analysis

Comparison 39 "Healer cream" vs Lignocaine, Outcome 1 NON ‐ healing.

39.2. Analysis

Comparison 39 "Healer cream" vs Lignocaine, Outcome 2 Headache.

40.1. Analysis

Comparison 40 "Healer Cream" vs GTN, Outcome 1 NON ‐ Healing.

40.2. Analysis

Comparison 40 "Healer Cream" vs GTN, Outcome 2 Headache.

41.1. Analysis

Comparison 41 Lignocaine + Botox vs Lignocaine + GTN, Outcome 1 NON ‐ Healing.

41.2. Analysis

Comparison 41 Lignocaine + Botox vs Lignocaine + GTN, Outcome 2 Headache.

42.1. Analysis

Comparison 42 Botox vs Botox + GTN, Outcome 1 NON ‐ Healing.

42.2. Analysis

Comparison 42 Botox vs Botox + GTN, Outcome 2 Minor incontinence.

43.1. Analysis

Comparison 43 GTN vs GTN + cryothermal dilators, Outcome 1 NON ‐ Healing.

43.2. Analysis

Comparison 43 GTN vs GTN + cryothermal dilators, Outcome 2 Headache.

44.1. Analysis

Comparison 44 Botox injection site location, Outcome 1 Non healing of the fissure.