Skip to main content

Advertisement

SpringerLink
Log in

A systematic review and meta-analysis of the efficacy of topical sphincterotomy treatments for anal fissure

  • Review
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background

Anal fissure is a common condition that can be treated medically or surgically. Chemical sphincterotomy is often used before surgical intervention. This study aims to evaluate the effectiveness of topical agents for chemical sphincterotomy on healing of anal fissures and side-effects.

Methods

A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant systematic review was performed using MEDLINE, EMBASE, Scopus, and CENTRAL databases. Eligible studies included randomized controlled trials which compared topical sphincterotomy agents with topical placebo agents or each other. Studies that included surgical treatments were excluded. Overall evidence was synthesized according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

Results

Thirty-seven studies met the study selection criteria. Seventeen studies show that glyceryl trinitrate (GTN) was significantly more likely to heal anal fissure than placebo (relative risk (RR) = 1.96, 95% confidence interval (95%CI) = 1.35–2.84, I2 = 80%). Eleven studies showed a marginally significant difference between healing rates for diltiazem vs GTN, RR = 1.16, (1.01–1.33) I2 = 48%. There was no significant difference in healing between diltiazem and placebo, RR = 1.65, (0.64–4.23), I2 = 92%. GTN significantly reduced pain on the visual analog scale compared to the placebo group, MD–0.97 (–1.64 to –0.29) I2 = 92%. There was high certainty of evidence that GTN was significantly more likely to cause headache than placebo (RR = 2.73 (1.82–4.10) I2 = 58%) and diltiazem RR = 6.88 (2.19–21.63) I2 = 17%.

Conclusion

There is low certainty evidence topical nitrates are an effective treatment for anal fissure healing and pain reduction compared to placebo. Despite widespread use of topical diltiazem, more evidence is required to establish the effectiveness of calcium channel blockers compared to placebo.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Keighley MR, Williams NS (2018) Keighley & Williams' Surgery of the Anus, Rectum and Colon: Two-volume set: CRC Press

  2. Lund J, Scholefield J (1996) Aetiology and treatment of anal fissure. Br J Surg 83(10):1335–1344

    Article  CAS  Google Scholar 

  3. Siddiqui J, Fowler GE, Zahid A, Brown K, Young CJ (2019) Treatment of anal fissure: a survey of surgical practice in Australia and New Zealand. Colorectal Dis 21(2):226–233

    Article  CAS  Google Scholar 

  4. Stewart DB Sr, Gaertner W, Glasgow S, Migaly J, Feingold D, Steele SR (2017) Clinical practice guideline for the management of anal fissures. Dis Colon Rectum 60(1):7–14

    Article  Google Scholar 

  5. Ebinger SM, Hardt J, Warschkow R, Schmied BM, Herold A, Post S et al (2017) Operative and medical treatment of chronic anal fissures-a review and network meta-analysis of randomized controlled trials. J Gastroenterol 52(6):663–676

    Article  Google Scholar 

  6. Nelson RL, Thomas K, Morgan J, Jones A (2012) Non surgical therapy for anal fissure. Cochrane database of systematic reviews. (2)

  7. Altomare DF, Rinaldi M, Milito G, Arcana F, Spinelli F, Nardelli N et al (2000) Glyceryl trinitrate for chronic anal fissure - Healing or headache? - Results of a multicenter, randomized, placebo-controlled, double-blind trial. Dis Colon Rectum 43(2):174–181

    Article  CAS  Google Scholar 

  8. Antropoli C, Perrotti P, Rubino M, Martino A, De Stefano G, Migliore G et al (1999) Nifedipine for local use in conservative treatment of anal fissures: preliminary results of a multicenter study. Dis Colon Rectum 42(8):1011–1015

    Article  CAS  Google Scholar 

  9. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J et al (2011) GRADE guidelines: 1. Introduction—GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 64(4):383–94

  10. Wan X, Wang W, Liu J, Tong T (2014) Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 14(1):1–13

    Article  Google Scholar 

  11. Team RC (2013) R: A language and environment for statistical computing

  12. Schwarzer G (2007) meta: An R package for meta-analysis. R news 7(3):40–45

    Google Scholar 

  13. Sterne JA, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I et al (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. bmj 366

  14. McGuinness LA, Higgins JP (2021) Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments. Research Synthesis Methods 12(1):55–61

    Article  Google Scholar 

  15. Ahmad J, Andrabi SI, Rathore MA (2007) Comparison of topical glyceryl trinitrate with lignocaine ointment for treatment of anal fissure: a randomised controlled trial. Int J Surg 5(6):429–432

    Article  CAS  Google Scholar 

  16. Bacher H, Mischinger HJ, Werkgartner G, Cerwenka H, El-Shabrawi A, Pfeifer J et al (1997) Local nitroglycerin for treatment of anal fissures: An alternative to lateral sphincterotomy? Dis Colon Rectum 40(7):840–845

    Article  CAS  Google Scholar 

  17. Bailey HR, Beck DE, Billingham RP, Binderow SR, Gottesman L, Hull TL et al (2002) A study to determine the nitroglycerin ointment dose and dosing interval that best promote the healing of chronic anal fissures. Dis Colon Rectum 45(9):1192–1199

    Article  Google Scholar 

  18. Berry SM, Barish CF, Bhandari R, Clark G, Collins GV, Howell J et al (2013) Nitroglycerin 0.4% ointment vs placebo in the treatment of pain resulting from chronic anal fissure: A randomized, double-blind, placebo-controlled study. BMC Gastroenterology. 13(1)

  19. Carapeti EA, Kamm MA, McDonald PJ, Chadwick SJ, Melville D, Phillips RK (1999) Randomised controlled trial shows that glyceryl trinitrate heals anal fissures, higher doses are not more effective, and there is a high recurrence rate. Gut 44(5):727–730

    Article  CAS  Google Scholar 

  20. Emami MH, Sayedyahossein S, Aslani A (2008) Safety and efficacy of new glyceryl trinitrate suppository formula: First double blind placebo-controlled clinical trial. Dis Colon Rectum 51(7):1079–1083

    Article  CAS  Google Scholar 

  21. Joda AE, Al-Mayoof AF (2017) Efficacy of nitroglycerine ointment in the treatment of pediatric anal fissure. J Pediatr Surg 52(11):1782–1786

    Article  Google Scholar 

  22. Kennedy ML, Sowter S, Nguyen H, Lubowski DZ (1999) Glyceryl trinitrate ointment for the treatment of chronic anal fissure - Results of a placebo-controlled trial and long-term follow-up. Dis Colon Rectum 42(8):1000–1006

    Article  CAS  Google Scholar 

  23. Lund JN, Scholefield JH (1997) A randomised, prospective, double-blind, placebo-controlled trial of glyceryl trinitrate ointment in treatment of anal fissure. Lancet 349(9044):11–14

    Article  CAS  Google Scholar 

  24. Lysy J, Israelit-Yatzkan Y, Sestiery-Ittah M, Weksler-Zangen S, Keret D, Goldin E (2001) Topical nitrates potentiate the effect of botulinum toxin in the treatment of patients with refractory anal fissure. Gut 48(2):221–224

    Article  CAS  Google Scholar 

  25. Scholefield JH, Bock JU, Marla B, Richter HJ, Athanasiadis S, Prols M et al (2003) A dose finding study with 0.1%, 0.2%, and 0.4% glyceryl trinitrate ointment in patients with chronic anal fissures. Gut. 52(2):264–9

  26. Sonmez K, Demirogullari B, Ekingen G, Turkyilmaz Z, Karabulut R, Basaklar AC et al (2002) Randomized, placebo-controlled treatment of anal fissure by lidocaine, EMLA, and GTN in children. J Pediatr Surg 37(9):1313–1316

    Article  Google Scholar 

  27. Tander B, Guven A, Demirbag S, Ozkan Y, Ozturk H, Cetinkursun S (1999) A prospective, randomized, double-blind, placebo-controlled trial of glyceryl-trinitrate ointment in the treatment of children with anal fissure. J Pediatr Surg 34(12):1810–1812

    Article  CAS  Google Scholar 

  28. Tankova L, Yoncheva K, Kovatchki D, Doytchinova I (2009) Topical anal fissure treatment: Placebo-controlled study of mononitrate and trinitrate therapies. Int J Colorectal Dis 24(4):461–464

    Article  Google Scholar 

  29. Werre AJ, Palamba HW, Bilgen EJS, Eggink WF (2003) Isosorbide dinitrate in the treatment of anal fissure: a randomised, prospective, double blind, placebo-controlled trial. Eur J Surg 167(5):382–385

    Google Scholar 

  30. Yakoot M, Salaam MA (2009) Study of efficacy and safety of a new local cream (“ healer”) in the treatment of chronic anal fissure: a prospective, randomized, single-blind, comparative study. Arq Gastroenterol 46(3):179–182

    Article  Google Scholar 

  31. Shrivastava UK, Jain BK, Kumar P, Saifee Y (2007) A comparison of the effects of diltiazem and glyceryl trinitrate ointment in the treatment of chronic anal fissure: a randomized clinical trial. Surg Today 37(6):482–485

    Article  CAS  Google Scholar 

  32. Ala S, Saeedi M, Hadianamrei R, Ghorbanian A (2012) Topical Diltiazem vs. topical Glyceril trinitrate in the treatment of chronic anal fissure: A prospective, randomized, double-blind trial. Acta Gastro-Enterologica Belgica. 75(4):438–42

  33. Bielecki K, Kolodziejczak M (2003) A prospective randomized trial of diltiazem and glyceryltrinitrate ointment in the treatment of chronic anal fissure. Colorectal Dis 5(3):256–257

    Article  CAS  Google Scholar 

  34. Cevik M, Boleken ME, Koruk I, Ocal S, Balcioglu ME, Aydinoglu A et al (2012) A prospective, randomized, double-blind study comparing the efficacy of diltiazem, glyceryl trinitrate, and lidocaine for the treatment of anal fissure in children. Pediatr Surg Int 28(4):411–416

    Article  Google Scholar 

  35. Jawaid M, Masood Z, Salim M (2009) Topical diltiazem hydrochloride and glyceryl trinitrate in the treatment of chronic anal fissure. J College of Phys and Surg Pakistan 19(10):614–617

    PubMed  Google Scholar 

  36. Khan MS, Akbar I, Zeb J, Ahmad S, Khan A (2017) Outcome Of 0.2% Glyceryltrinitrate Cream Versus 2% Diltiazem Cream In The Treatment Of Chronic Anal Fissure. J Ayub Med College, Abbott. 29(2):280‐4

  37. Kocher HM, Steward M, Leather AJ, Cullen PT (2002) Randomized clinical trial assessing the side-effects of glyceryl trinitrate and diltiazem hydrochloride in the treatment of chronic anal fissure. Br J Surg 89(4):413–417

    Article  CAS  Google Scholar 

  38. Sanei B, Mahmoodieh M, Masoudpour H (2009) Comparison of topical glyceryl trinitrate with diltiazem ointment for treatment of chronic anal fissure. A randomized clinical trial. Annali italiani di chirurgia. 80(5):379–83

  39. Tomar V, Saxena A (2014) Establishing the Superiority of Topical Diltiazem over Glyceryl Trinitrate in the Treatment of Chronic Anal Fissure: a Prospective Analytical Study. Global J Surg 2(3):37–41

    Google Scholar 

  40. Alshehri A, Barghouthi R, Albanyan S, Alayed M, Alsubaie H, Alhayyan R et al (2020) A prospective, double-blind, randomized, placebo-controlled trial comparing the efficacy of polyethylene glycol versus polyethylene glycol combined with topical diltiazem for treating anal fissure in children. J Ped Surg

  41. Hanumanthappa MB, Suvarna R, Guruprasad RD (2012) Topical diltiazem is superior to topical lignocaine in the treatment of chronic anal fissure: Results of a prospective comparative study. J Clin Diagn Res 6(6):1014–1017

    CAS  Google Scholar 

  42. Tavakoli-Dastjerdi S, Motavasselian M, Emami SA, Mansourian M, Sahebkar A, Teimouri A (2019) Efficacy of a combination of herbal gel versus topical diltiazem (2%) in chronic anal fissure healing: A randomized double-blind clinical trial. J Herb Med Pharmacol 8(2):139–145

    Article  Google Scholar 

  43. Golfam F, Golfam P, Khalaj A, Mortaz SSS (2010) The effect of topical nifedipine in treatment of chronic anal fissure. Acta Med Iran 48(5):295–299

    CAS  PubMed  Google Scholar 

  44. Perrotti P, Bove A, Antropoli C, Molino D, Antropoli M, Balzano A et al (2002) Topical nifedipine with lidocaine ointment vs. active control for treatment of chronic anal fissure: Results of a prospective, randomized, double-blind study. Diseases of the Colon and Rectum. 45(11):1468–75

  45. Ezri T, Susmallian S (2003) Topical nifedipine vs. topical glyceryl trinitrate for treatment of chronic anal fissure. Diseases of the colon & rectum. 46(6):805–8

  46. Khaledifar B, Mahmoudi MYA, Mobasheri M (2015) A double-blind randomized trial comparing the effectiveness and safety of nifedipine and isosorbide dinitrate in chronic anal fissure. The Malaysian journal of medical sciences: MJMS 22(5):42

    PubMed  PubMed Central  Google Scholar 

  47. Pardhan A, Azami R, Mazahir S, Murtaza G (2014) Diltiazem vs. glyceryl tri-nitrate for symptomatic relief in anal fissure: a randomised clnical study. JPMA The J Pakistan Med Assoc. 64(5):510‐3

  48. Bansal A, Yadav PK, Godara R, Pal N, Tripura R (2016) Comparative evaluation of 0.2% glyceryl trinitrate vs. 2% diltiazem ointment in treatment of chronic anal fissure treatment-a randomized trial. Hellenic J Surg. 88(1):25–30

  49. Bulus H, Varol N, Tas A, Coskun A (2013) Comparison of topical isosorbide mononitrate, topical diltiazem, and their combination in the treatment of chronic anal fissure. Asian J Surg 36(4):165–169

    Article  Google Scholar 

  50. Nelson R, Manuel D, Gumienny C, Spencer B, Patel K, Schmitt K et al (2017) A systematic review and meta-analysis of the treatment of anal fissure. Tech Coloproctol 21(8):605–625

    Article  CAS  Google Scholar 

  51. Shah M, Sandler L, Rai V, Sharma C, Raghavan L (2013) Quality of compounded topical 2% diltiazem hydrochloride formulations for anal fissure. World J Gastroenterol: WJG 19(34):5645

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, South Auckland Clinical Campus, The University of Auckland, Auckland, New Zealand

    James Z. Jin, Molly-Olivia Hardy, Hanson Unasa, Melbourne Mauiliu-Wallis & Andrew G. Hill

  2. Department of Surgery, Counties Manukau District Health Board, Manukau, New Zealand

    Hanson Unasa, Melbourne Mauiliu-Wallis, Maree Weston, Andrew Connolly, Primal (Parry) Singh & Andrew G. Hill

Authors
  1. James Z. Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Molly-Olivia Hardy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hanson Unasa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Melbourne Mauiliu-Wallis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maree Weston
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrew Connolly
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Primal (Parry) Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Andrew G. Hill
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James Z. Jin.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jin, J.Z., Hardy, MO., Unasa, H. et al. A systematic review and meta-analysis of the efficacy of topical sphincterotomy treatments for anal fissure. Int J Colorectal Dis 37, 1–15 (2022). https://doi.org/10.1007/s00384-021-04040-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-021-04040-3

Keywords

Search

Navigation