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The effect of antibiotic use on endodontic post-operative pain and flare-up rate: a systematic review with meta-analysis

A Correction to this article was published on 24 June 2022

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Abstract

Aim Antibiotics are widely used to prevent flare-ups after endodontic treatment of non-vital teeth. This systematic review assessed the effect of antibiotic administration on post-endodontic treatment pain and flare-up rate.

Methods Five major databases including Web of Science, Cochrane Library, PubMed, Scopus and Embase were searched to identify randomised clinical trials (RCTs) published until September 2020. Retrieved papers were critically appraised using the revised Cochrane risk of bias tool (RoB 2). To reduce the clinical heterogeneity, the included studies were divided into two groups: studies on symptomatic non-vital teeth and studies on asymptomatic non-vital teeth. The primary outcomes were 'post-operative pain' and 'flare-up rate'. The data of included studies were statistically combined through meta-analysis using random-effect model. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence.

Results Six RCTs involving two RCTs (N = 61) on symptomatic teeth and four RCTs (N = 310) on asymptomatic teeth were included. In two RCTs on asymptomatic teeth, prophylactic antibiotic had been used, while in the remaining two RCTs, antibiotics had been administered after treatment. Quantitative synthesis of the RCTs showed that antibiotic administration following endodontic treatment of symptomatic non-vital teeth has no effect on pain severity at 24 hours following treatment (weighted mean difference [WMD] = -0.03; 95% confidence interval [CI]: -0.53 to 0.47), and the use of antibiotics before endodontic treatment of asymptomatic non-vital teeth has no effect on flare-up rate (relative risk [RR] = 0.58; 95% CI: 0.22-1.54). The GRADE approach revealed that the overall quality of evidence on the topic is low.

Conclusions The antibiotic administration following endodontic treatment of symptomatic non-vital teeth has no effect on pain severity at 24 hours following treatment. Also, prophylactic antibiotics are ineffective in reducing the flare-up rate following treatment of asymptomatic non-vital teeth. However, to evaluate the effect of post-treatment antibiotics on flare-up rate in asymptomatic non-vital teeth, more high-quality RCTs are needed.

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References

  1. Siqueira Jr J F. Microbial causes of endodontic flare-ups. Int Endod J 2003; 36: 453-463.

  2. Mata E, Koren L Z, Morse D R, Sinai I H. Prophylactic use of penicillin V in teeth with necrotic pulps and asymptomatic periapical radiolucencies. Oral Surg Oral Med Oral Pathol 1985; 60: 201-207.

  3. Aoun C, El Osta N, Naaman A, Zogheib C, Khalil I. Post-endodontic Flare-ups after a Single-visit Treatment Using the FUI Scoring Method and Associated Factors: A Clinical Prospective Study. J Contemp Dent Pract 2019; 20: 1033-1040.

  4. Azim A A, Azim K A, Abbott P V. Prevalence of inter-appointment endodontic flare-ups and host-related factors. Clin Oral Investig 2017; 21: 889-894.

  5. Pai S, Vivekananda Pai A R, Thomas M S, Bhat V. Effect of calcium hydroxide and triple antibiotic paste as intracanal medicaments on the incidence of inter-appointment flare-up in diabetic patients: An in vivo study. J Conserv Dent 2014; 17: 208-211.

  6. Pickenpaugh L, Reader A, Beck M, Meyers W J, Peterson L J. Effect of prophylactic amoxicillin on endodontic flare-up in asymptomatic, necrotic teeth. J Endod 2001; 27: 53-56.

  7. Siqueira Jr J F, Rocas I N, Favieri A et al. Incidence of post-operative pain after intracanal procedures based on an antimicrobial strategy. J Endod 2002; 28: 457-460.

  8. Tsesis I, Faivishevsky V, Fuss Z, Zukerman O. Flare-ups after endodontic treatment: a meta-analysis of literature. J Endod 2008; 34: 1177-1181.

  9. Seltzer S, Naidorf I J. Flare-ups in endodontics: II. Therapeutic measures. J Endod 1985; 11: 559-567.

  10. Torabinejad M, Kettering J D, McGraw J C, Cummings R R, Dwyer T G, Tobias T S. Factors associated with endodontic interappointment emergencies of teeth with necrotic pulps. J Endod 1988; 14: 261-266.

  11. Jayakodi H, Kailasam S, Kumaravadivel K, Thangavelu B, Mathew S. Clinical and pharmacological management of endodontic flare-up. J Pharm Bioallied Sci 2012; 4: S294-S298.

  12. Akhlaghi N, Azarshab M, Akhoundi N, Meraji N. The effect of ketorolac buccal infiltration on post-operative endodontic pain: a prospective, double-blind, randomized, controlled clinical trial. Quintessence Int 2019; 50: 540-546.

  13. Al-Rawhani A H, Gawdat S I, Wanees Amin S A. Effect of Diclofenac Potassium Premedication on Postendodontic Pain in Mandibular Molars with Symptomatic Irreversible Pulpitis: A Randomized Placebo-Controlled Double-Blind Trial. J Endod 2020; 46: 1023-1031.

  14. Mangal S, Mathew S, Murthy B V S, Hegde S, Dinesh K, Ramesh P. The efficacy of transdermal and oral diclofenac for post-endodontic pain control: A randomised controlled trial. Indian J Dent Res 2020; 31: 53-56.

  15. Shantiaee Y, Mahjour F, Dianat O. Efficacy comparison of periapical infiltration injection of dexamethasone, morphine and placebo for post-operative endodontic pain. Int Dent J 2012; 62: 74-78.

  16. Yavari H R, Jafari F, Jamloo H, Hallaj-Nezhadi S, Jafari S. The Effect of Submucosal Injection of Corticosteroids on Pain Perception and Quality of Life after Root Canal Treatment of Teeth with Irreversible Pulpitis: A Randomized Clinical Trial. J Endod 2019; 45: 477-482.

  17. Ahmed Y E, Emara R S, Sarhan S M et al. Post-treatment endodontic pain following occlusal reduction in mandibular posterior teeth with symptomatic irreversible pulpitis and sensitivity to percussion: a single-centre randomized controlled trial. Int Endod J 2020; 53: 1170-1180.

  18. Coelho M S, Vilas-Boas L, Tawil P Z. The effects of photodynamic therapy on post-operative pain in teeth with necrotic pulps. Photodiagnosis Photodyn Ther 2019; 27: 396-401.

  19. Doğanay Yıldız E, Arslan H. Effect of Low-level Laser Therapy on Post-operative Pain in Molars with Symptomatic Apical Periodontitis: A Randomized Placebo-controlled Clinical Trial. J Endod 2018; 44: 1610-1615.

  20. Samir Abouelenien S, Mohamed Ibrahim S, Gameel Shaker O, Mohamed Ahmed G. Evaluation of post-operative pain in infected root canals after using double antibiotic paste versus calcium hydroxide as intra-canal medication: A randomized controlled trial. F1000Res 2018; 7: 1768.

  21. Seltzer S, Naidorf I J. Flare-ups in endodontics: II. Therapeutic measures. J Endod 2004; 30: 482-488.

  22. Negm M M. Intracanal use of a corticosteroid-antibiotic compound for the management of posttreatment endodontic pain. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001; 92: 435-439.

  23. Kashefinejad M, Harandi A, Eram S, Bijani A. Comparison of Single Visit Post Endodontic Pain Using Mtwo Rotary and Hand K-File Instruments: A Randomized Clinical Trial. J Dent (Tehran) 2016; 13: 10-17.

  24. Sun C, Sun J, Tan M, Hu B, Gao X, Song J. Pain after root canal treatment with different instruments: A systematic review and meta-analysis. Oral Dis 2018; 24: 908-919.

  25. Iqbal M, Kurtz E, Kohli M. Incidence and factors related to flare-ups in a graduate endodontic programme. Int Endod J 2009; 42: 99-104.

  26. Shamszadeh S, Shirvani A, Asgary S. Does occlusal reduction reduce post-endodontic pain? A systematic review and meta-analysis. J Oral Rehabil 2020; 47: 528-535.

  27. Arslan H, Seckin F, Kurklu D, Karatas E, Yanikoglu N, Capar I D. The effect of various occlusal reduction levels on post-operative pain in teeth with symptomatic apical periodontitis using computerized analysis: a prospective, randomized, double-blind study. Clin Oral Investig 2017; 21: 857-863.

  28. Alonaizan F A, AlFawaz Y F. Is phototherapy effective in the management of post-operative endodontic pain? A systematic review of randomized controlled clinical trials. Photodiagnosis Photodyn Ther 2019; 26: 53-58.

  29. Chen Y, Chen X L, Zou X L, Chen S Z, Zou J, Wang Y. Efficacy of low-level laser therapy in pain management after root canal treatment or retreatment: a systematic review. Lasers Med Sci 2019; 34: 1305-1316.

  30. Emara R S, Abou El Nasr H M, El Boghdadi R M. Evaluation of post-operative pain intensity following occlusal reduction in teeth associated with symptomatic irreversible pulpitis and symptomatic apical periodontitis: a randomized clinical study. Int Endod J 2019; 52: 288-296.

  31. Iranmanesh F, Parirokh M, Haghdoost A A, Abbott P V. Effect of Corticosteroids on Pain Relief Following Root Canal Treatment: A Systematic Review. Iran Endod J 2017; 12: 123-130.

  32. Nath R, Daneshmand A, Sizemore D, Guo J, Enciso R. Efficacy of corticosteroids for post-operative endodontic pain: A systematic review and meta-analysis. J Dent Anesth Pain Med 2018; 18: 205-221.

  33. Henry M, Reader A, Beck M. Effect of penicillin on post-operative endodontic pain and swelling in symptomatic necrotic teeth. J Endod 2001; 27: 117-123.

  34. Alsomadi L, Al Habahbeh R. Role of prophylactic antibiotics in the management of post-operative endodontic pain. J Contemp Dent Pract 2015; 16: 939-943.

  35. Rimmer A. Intracanal medications and antibiotics in the control of interappointment flare-ups. Quintessence Int 1991; 22: 997-1005.

  36. Morse D R, Furst M L, Belott R M, Lefkowitz R D, Spritzer I B, Sideman B H. Prophylactic penicillin versus penicillin taken at the first sign of swelling in cases of asymptomatic pulpal-periapical lesions: a comparative analysis. Oral Surg Oral Med Oral Pathol 1988; 65: 228-232.

  37. Morse D R, Furst M L, Lefkowitz RD, D'Angelo D, Esposito J V. A comparison of erythromycin and cefadroxil in the prevention of flare-ups from asymptomatic teeth with pulpal necrosis and associated periapical pathosis. Oral Surg Oral Med Oral Pathol 1990; 69: 619-630.

  38. Morse D, Koren L, Esposito J, Goldberg J, Sinai I, Furst M. Asymptomatic teeth with necrotic pulps and associated periapical radiolucencies: Relationship of flare-ups to endodontic instrumentation, antibiotic usage and stress in three separate practices at three different time periods: Part IV - Comparative examination and discussion. Int J Psychsom 1986; 33: 64-81.

  39. Morse D R, Furst M L, Belott R M, Lefkowitz R D, Spritzer I B, Sideman B H. A prospective randomized trial comparing periapical instrumentation to intracanal instrumentation in cases of asymptomatic pulpal-periapical lesions. Oral Surg Oral Med Oral Pathol 1987; 64: 734-741.

  40. Torabinejad M, Dorn S O, Eleazer P D et al. Effectiveness of various medications on post-operative pain following root canal obturation. J Endod 1994; 20: 427-431.

  41. Al Masan A A, Dummer P M H, Farnell D J J, Vianna M E. Antibiotic prescribing for endodontic therapies: a comparative survey between general dental practitioners and final year Bachelor of Dental Surgery students in Cardiff UK. Int Endod J 2018; 51: 717-728.

  42. Bidar M, Gharechahi M, Soleimani T, Eslami N. A Survey over the Dentists' and Endodntists' Approaches towards the Management of Endodontic Emergencies in Mashhad, Iran. Iran Endod J 2015; 10: 256-262.

  43. Buttar R, Aleksejūnienė J, Coil J. Antibiotic and Opioid Analgesic Prescribing Patterns of Dentists in Vancouver and Endodontic Specialists in British Columbia. J Can Dent Assoc 2017; 83: h8.

  44. Germack M, Sedgley C M, Sabbah W, Whitten B. Antibiotic Use in 2016 by Members of the American Association of Endodontists: Report of a National Survey. J Endod 2017; 43: 1615-1622.

  45. Segura-Egea J J, Velasco-Ortega E, Torres-Lagares D, Velasco-Ponferrada M C, Monsalve-Guil L, Llamas-Carreras J M. Pattern of antibiotic prescription in the management of endodontic infections among Spanish oral surgeons. Int Endod J 2010; 43: 342-350.

  46. Yingling N M, Byrne B E, Hartwell G R. Antibiotic use by members of the American Association of Endodontists in the year 2000: report of a national survey. J Endod 2002; 28: 396-404.

  47. Akbar I. Efficacy of prophylactic use of antibiotics to avoid flare up during root canal treatment of non-vital teeth: a randomized clinical trial. J Clin Diagn Res 2015; DOI: 10.7860/JCDR/2015/12046.5620.

  48. Shah S I, Qayyum Z, Shah S A, Khan S, Pasha F. Prophylactic use of antibiotics to prevent flare - up in endodontic treatment. Pakist Oral Dental J 2011; 31: 427-431.

  49. Walton R E, Chiappinelli J. Prophylactic penicillin: effect on posttreatment symptoms following root canal treatment of asymptomatic periapical pathosis. J Endod 1993; 19: 466-470.

  50. Moher D, Liberati A, Tetzlaff J, Altman D G. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009; 62: 1006-1012.

  51. Shamseer L, Moher D, Clarke M et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2015; DOI: 10.1136/bmj.g7647.

  52. Hargreaves K M, Berman L H. Cohen's Pathways of the Pulp Expert Consult. St Louis: Elsevier Health Sciences, 2015.

  53. Ingle J I. Ingle's Endodontics 6. Hamilton: PMPH-USA, 2008.

  54. Sterne J A C, Savović J, Page M J et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019; DOI: 10.1136/bmj.l4898.

  55. Higgins J P, Thompson S G. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-1558.

  56. Hardy R J, Thompson S G. A likelihood approach to meta-analysis with random effects. Stat Med 1996; 15: 619-629.

  57. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634.

  58. Begg C B, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50: 1088-1101.

  59. Harbourd R M, Egger M, Sterne J A. A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints. Stat Med 2006; 25: 3443-3457.

  60. Atkins D, Best D, Briss P A et al. Grading quality of evidence and strength of recommendations. BMJ 2004; 328: 1490.

  61. Guyatt G H, Oxman A D, Vist G E et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008; 336: 924-926.

  62. Fouad A F, Rivera E M, Walton R E. Penicillin as a supplement in resolving the localized acute apical abscess. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996; 81: 590-595.

  63. Morse D R, Furst M L, Belott R M, Lefkowitz R D, Spritzer I B, Sideman B H. Infectious flare-ups and serious sequelae following endodontic treatment: a prospective randomized trial on efficacy of antibiotic prophylaxis in cases of asymptomatic pulpal-periapical lesions. Oral Surg Oral Med Oral Pathol 1987; 64: 96-109.

  64. Rehman K, Akber I, Qazi J. Role of antibiotics in control of post-endodontic pain: cases of symptomatic irreversible pulpitis and periapical periodontitis: a randomized control clinical trial. J Khyber College Dentistry 2012; 3: 12-16.

  65. Contardo L, Meneguzzi E, Cadenaro M, Di Lenarda R. Clinical evaluation of antibiotic prophylaxis before endodontic treatment of necrotic teeth. Minerva Stomatol 2005; 54: 153-160.

  66. Alves V D O. Endodontic flare-ups: A prospective study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; DOI: 10.1016/j.tripleo.2010.05.014.

  67. Martin-Gonzalez J, Echevarria-Perez M, Sanchez-Dominguez B et al. Influence of root canal instrumentation and obturation techniques on intra-operative pain during endodontic therapy. Med Oral Patol Oral Cir Bucal 2012; DOI: 10.4317/medoral.18234.

  68. Walton R, Fouad A. Endodontic interappointment flare-ups: a prospective study of incidence and related factors. J Endod 1992; 18: 172-177.

  69. Abbott A A, Koren L Z, Morse D R, Sinai I H, Doo R S, Furst M L. A prospective randomized trial on efficacy of antibiotic prophylaxis in asymptomatic teeth with pulpal necrosis and associated periapical pathosis. Oral Surg Oral Med Oral Pathol 1988; 66: 722-733.

  70. Jorgensen L, Paludan-Muller A S, Laursen D R et al. Evaluation of the Cochrane tool for assessing risk of bias in randomized clinical trials: overview of published comments and analysis of user practice in Cochrane and non-Cochrane reviews. Syst Rev 2016; 5: 80.

  71. Sipaviciute E, Maneliene R. Pain and flare-up after endodontic treatment procedures. Stomatologija 2014; 16: 25-30.

  72. Aminoshariae A, Kulild J C. Evidence-based recommendations for antibiotic usage to treat endodontic infections and pain A systematic review of randomized controlled trials. J Am Dent Assoc 2016; 147: 186-191.

  73. Nagle D, Reader A, Beck M, Weaver J. Effect of systemic penicillin on pain in untreated irreversible pulpitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000; 90: 636-640.

  74. Guyatt G, Oxman A D, Akl E A et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011; 64: 383-394.

  75. Bolfoni M R, Pappen F G, Pereira-Cenci T, Jacinto R C. Antibiotic prescription for endodontic infections: a survey of Brazilian Endodontists. Int Endod J 2018; 51: 148-156.

  76. Alós J I. Antibiotic resistance: A global crisis. Enferm Infecc Microbiol Clin 2015; 33: 692-699.

  77. Blumenthal K G, Peter J G, Trubiano J A, Phillips E J. Antibiotic allergy. Lancet 2019; 393: 183-198.

  78. Davies J, Davies D. Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev 2010; 74: 417-433.

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Acknowledgements

The authors thank Research Centre for Evidence-Based Medicine (EBM) of Tabriz University of Medical Sciences for financial support of this research.

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Milani, A., Froughreyhani, M., Taghiloo, H. et al. The effect of antibiotic use on endodontic post-operative pain and flare-up rate: a systematic review with meta-analysis. Evid Based Dent (2022). https://doi.org/10.1038/s41432-021-0205-z

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