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Effect of Glyceryl Trinitrate Ointment on Pain Control After Hemorrhoidectomy: A Meta-analysis of Randomized Controlled Trials

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Abstract

Background

Hemorrhoidectomy is associated with postoperative pain and prolonged wound healing. Glyceryl trinitrate has been shown to decrease muscle spasm and increase anodermal blood flow. A meta-analysis of randomized controlled trials was conducted to evaluate the efficacy of topical glyceryl trinitrate application in pain relief after hemorrhoidectomy.

Methods

PubMed, EMBASE, Cochrane Library, Scopus, and ClinicalTrials.gov registries were searched for studies published before August 2015. Individual effect sizes were standardized, and a meta-analysis was conducted to calculate a pooled effect size using random effects models. Pain was assessed using a visual analog scale on days 1, 3, 7, and 14 after operation. Secondary outcomes included time taken to resume routine activities, wound healing at 3 weeks after operation, complication, and headache incidence.

Results

A total of 12 trials with 1095 patients were reviewed. Significant pain reduction was observed on days 1, 3, 7, and 14 after hemorrhoidectomy in the glyceryl trinitrate groups. Glyceryl trinitrate-treated patients appeared to resume routine activities earlier than those in the control group (weight mean difference −7.52; 95 % confidence interval: 16.13–1.08). The wound healing rates 3 weeks after operation were significant higher in the glyceryl trinitrate-treated groups than in the control group (risk ratio 1.79; 95 % confidence interval: 1.38–2.33). However, the incidence of headache significantly increased in the glyceryl trinitrate group (risk ratio 3.68; 95 % confidence interval: 1.62–8.34).

Conclusion

Topical application of glyceryl trinitrate effectively relieves pain and promotes wound healing after hemorrhoidectomy; however, the substantial headache incidence may limit extensive application.

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References

  1. MacRae HM, McLeod RS (1995) Comparison of hemorrhoidal treatment modalities: a meta-analysis. Dis Colon Rectum 38:687–694

    Article  PubMed  CAS  Google Scholar 

  2. Burch J, Epstein D, Sari AB et al (2009) Stapled haemorrhoidopexy for the treatment of haemorrhoids: a systematic review. Colorectal Dis 11:233–243; discussion 243

    Article  PubMed  CAS  Google Scholar 

  3. Cheetham MJ, Mortensen NJ, Nystrom PO, Kamm MA, Phillips RK (2000) Persistent pain and faecal urgency after stapled haemorrhoidectomy. Lancet 356:730–733

    Article  PubMed  CAS  Google Scholar 

  4. Ganio E, Altomare DF, Gabrielli F, Milito G, Canuti S (2001) Prospective randomized multicentre trial comparing stapled with open haemorrhoidectomy. Br J Surg 88:669–674

    Article  PubMed  CAS  Google Scholar 

  5. Goldstein ET, Williamson PR, Larach SW (1993) Subcutaneous morphine pump for postoperative hemorrhoidectomy pain management. Dis Colon Rectum 36:439–446

    Article  PubMed  CAS  Google Scholar 

  6. Schouten WR, Briel JW, Auwerda JJ, Boerma MO (1996) Anal fissure: new concepts in pathogenesis and treatment. Scand J Gastroenterol Suppl 218:78–81

    Article  PubMed  CAS  Google Scholar 

  7. Kua KB, Kocher HM, Kelkar A, Patel AG (2001) Effect of topical glyceryl trinitrate on anodermal blood flow in patients with chronic anal fissures. ANZ J Surg 71:548–550

    Article  PubMed  CAS  Google Scholar 

  8. Poh A, Tan KY, Seow-Choen F (2010) Innovations in chronic anal fissure treatment: a systematic review. World J Gastrointest Surg 2:231–241

    Article  PubMed  PubMed Central  Google Scholar 

  9. Utzig MJ, Kroesen AJ, Buhr HJ (2003) Concepts in pathogenesis and treatment of chronic anal fissure—a review of the literature. Am J Gastroenterol 98:968–974

    PubMed  CAS  Google Scholar 

  10. Di Vita G, Patti R, Arcara M, Petrone R, Davì V, Leo P (2004) A painless treatment for patients undergoing Milligan-Morgan haemorrhoidectomy. Ann Ital Chir 75:471–474

    PubMed  Google Scholar 

  11. Elton C, Sen P, Montgomery AC (2001) Initial study to assess the effects of topical glyceryl trinitrate for pain after haemorrhoidectomy. Int J Surg Investig 2:353–357

    PubMed  CAS  Google Scholar 

  12. Ratnasingham K, Uzzaman M, Andreani SM, Light D, Patel B (2010) Meta-analysis of the use of glyceryl trinitrate ointment after haemorrhoidectomy as an analgesic and in promoting wound healing. Int J Surg 8:606–611

    Article  PubMed  CAS  Google Scholar 

  13. Siddiqui MR, Daulatzai N (2011) Re: meta-analysis of the use of glyceryl trinitrate ointment after haemorrhoidectomy as an analgesic and in promoting wound healing. Int J Surg 9:272

    Article  PubMed  CAS  Google Scholar 

  14. Cross T, Bartlett L, Mushaya C, Ashour M, Ho YH (2012) Glyceryl trinitrate ointment did not reduce pain after stapled hemorrhoidectomy: a randomized controlled trial. Int Surg 97:112–119

    Article  PubMed  PubMed Central  Google Scholar 

  15. Franceschilli L, D’Ugo S, de Luca E et al (2013) Role of 0.4% glyceryl trinitrate ointment after haemorrhoidectomy: results of a prospective randomised study. Int J Colorectal Dis 28:365–369

    Article  PubMed  Google Scholar 

  16. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. www.cochrane-handbook.org

  17. Liberati A, Altman DG, Tetzlaff J et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62:e1–e34

    Article  PubMed  Google Scholar 

  18. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  PubMed  CAS  Google Scholar 

  19. Hwang DY, Yoon SG, Kim HS, Lee JK, Kim KY (2003) Effect of 0.2 percent glyceryl trinitrate ointment on wound healing after ahemorrhoidectomy: results of a randomized, prospective, double-blind, placebo-controlled trial. Dis Colon Rectum 46:950–954

    Article  PubMed  Google Scholar 

  20. Karanlik H, Akturk R, Camlica H, Asoglu O (2009) The effect of glyceryl trinitrate ointment on posthemorrhoidectomy pain and wound healing: results of a randomized, double-blind, placebo-controlled study. Dis Colon Rectum 52:280–285

    Article  PubMed  Google Scholar 

  21. Mari FS, Nigri G, Dall’Oglio A et al (2013) Topical glyceryl trinitrate ointment for pain related to anal hypertonia after stapled hemorrhoidopexy: a randomized controlled trial. Dis Colon Rectum 56:768–773

    Article  PubMed  Google Scholar 

  22. Patti R, Arcara M, Padronaggio D et al (2005) Efficacy of topical use of 0.2% glyceryl trinitrate in reducing post-haemorrhoidectomy pain and improving wound healing. Chir Ital 57:77–85

    PubMed  Google Scholar 

  23. Patti R, Almasio PL, Arcara M et al (2006) Botulinum toxin vs. topical glyceryl trinitrate ointment for pain control in patients undergoing hemorrhoidectomy: a randomized trial. Dis Colon Rectum 49:1741–1748

    Article  PubMed  Google Scholar 

  24. Tan KY, Sng KK, Tay KH, Lai JH, Eu KW (2006) Randomized clinical trial of 0.2 per cent glyceryl trinitrate ointment for wound healing and pain reduction after open diathermy haemorrhoidectomy. Br J Surg 93:1464–1468

    Article  PubMed  CAS  Google Scholar 

  25. Wasvary HJ, Hain J, Mosed-Vogel M, Bendick P, Barkel DC, Klein SN (2001) Randomized, prospective, double-blind, placebo-controlled trial of effect of nitroglycerin ointment on pain after hemorrhoidectomy. Dis Colon Rectum 44:1069–1073

    Article  PubMed  CAS  Google Scholar 

  26. Khan K, Waqas A, Akmal M, Mahmood S, Iqbal A (2014) Efficacy of combination of 0.2% GTN and lignocaine ointments in wound healing and pain relief after Milligan Morgan hemorrhoidectomy—a comparison with lignocaine and 0.2% GTN ointments separately. Int J Surg 12:329–333

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  28. 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 42:1000–1006

    Article  PubMed  CAS  Google Scholar 

  29. Altomare DF, Rinaldi M, Milito G et al (2000) Glyceryl trinitrate for chronic anal fissure–healing or headache? Results of a multicenter, randomized, placebo-controled, double-blind trial. Dis Colon Rectum 43:174–179; discussion 179–181

    Article  PubMed  CAS  Google Scholar 

  30. Nelson R (2004) A systematic review of medical therapy for anal fissure. Dis Colon Rectum 47:422–431

    Article  PubMed  Google Scholar 

  31. Nelson RL, Thomas K, Morgan J, Jones A (2012) Non surgical therapy for anal fissure. Cochrane Database Syst Rev 15(2):CD003431

    Google Scholar 

  32. Perrotti P, Dominici P, Grossi E, Cerutti R, Antropoli C (2010) Topical nifedipine with lidocaine ointment versus active control for pain after hemorrhoidectomy: results of a multicentre, prospective, randomized, double-blind study. Can J Surg 53:17–24

    PubMed  PubMed Central  Google Scholar 

  33. Silverman R, Bendick PJ, Wasvary HJ (2005) A randomized, prospective, double-blind, placebo-controlled trial of the effect of a calcium channel blocker ointment on pain after hemorrhoidectomy. Dis Colon Rectum 48:1913–1916

    Article  PubMed  Google Scholar 

  34. Sugimoto T, Tsunoda A, Kano N, Kashiwagura Y, Hirose K, Sasaki T (2013) A randomized, prospective, double-blind, placebo-controlled trial of the effect of diltiazem gel on pain after hemorrhoidectomy. World J Surg 37:2454–2457. doi:10.1007/s00268-013-2124-

    Article  PubMed  Google Scholar 

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Funding support

This work was supported by a research grant from Taipei Medical University and Shin Kong Wu Ho-Su Memorial Hospital (Grant no. SKH-TMU-103-07). The sponsoring organization was not involved in the study design, data analysis, or interpretation.

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Authors and Affiliations

  1. Department of Pharmacy, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

    Jen-Wei Liu & Chun-Yu Wang

  2. Center for Evidence-based Health Care, Taipei Medical University - Shuang Ho Hospital, New Taipei City, Taiwan

    Chao-Chun Lin & Ka-Wai Tam

  3. Division of Colorectal Surgery, Department of Surgery, Taipei Medical University - Shuang Ho Hospital, New Taipei City, Taiwan

    Kee-Thai Kiu

  4. Division of General Surgery, Department of Surgery, Taipei Medical University - Shuang Ho Hospital, New Taipei City, Taiwan

    Ka-Wai Tam

  5. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Ka-Wai Tam

  6. Center for Evidence-based Medicine, College of Medicine, Taipei Medical University - Shuang Ho Hospital, New Taipei City, Taiwan

    Ka-Wai Tam

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  1. Jen-Wei Liu
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  2. Chao-Chun Lin
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Correspondence to Ka-Wai Tam.

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The authors Jen-Wei Liu, Chao-Chun Lin, Kee-Thai Kiu, Chun-Yu Wang, and Ka-Wai Tam have no conflicts of interest or financial ties to disclose.

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Liu, JW., Lin, CC., Kiu, KT. et al. Effect of Glyceryl Trinitrate Ointment on Pain Control After Hemorrhoidectomy: A Meta-analysis of Randomized Controlled Trials. World J Surg 40, 215–224 (2016). https://doi.org/10.1007/s00268-015-3344-6

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  • DOI: https://doi.org/10.1007/s00268-015-3344-6

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