Clinical Oral Investigations

, Volume 22, Issue 7, pp 2581–2591 | Cite as

A randomized controlled clinical trial on the effectiveness of three different mouthrinses (chlorhexidine with or without alcohol and C31G), adjunct to periodontal surgery, in early wound healing

  • Anastasios M. GkatzonisEmail author
  • Spyridon I. Vassilopoulos
  • Ioannis K. Karoussis
  • Archontia Kaminari
  • Phoebus N. Madianos
  • Ioannis A. Vrotsos
Original Article



The use of chlorhexidine (CHX) with or without alcohol has been recommended for a number of clinical applications. On the other hand, there is a plethora of widely subscribed antiseptics, such as agent C31G (alkyl dimethyl glycine/alkyl dimethyl amine oxide), which has not yet been evaluated postsurgically. The effectiveness of three different mouthrinses (CHX with and without alcohol, C31G) in plaque control and early wound healing was compared postoperatively.

Materials and methods

In this, randomized, double-blind, controlled clinical trial 42 patients were allocated to three groups assigned to 2 weeks rinsing after non-regenerative periodontal flap surgery with or without osseous surgery with C31G (group A), alcohol-free CHX 0.12% (group B) or alcohol-based CHX 0.12% (group C). At days 7 and 14, plaque and early wound healing indices were recorded. At day 14, total bacterial counts were estimated utilizing real-time quantitative polymerase chain reaction (qPCR). Statistics included linear and generalized linear mixed models.


At day 7, healing response was not significantly different among groups. At day 14, group A revealed the highest while group C demonstrated the lowest plaque index values (B vs A, odds ratio—OR = 0.18, p = 0.012; C vs A, OR = 0.01, p < 0.001; C vs B, OR = 0.06, p < 0.001). Group C demonstrated the lowest bacterial counts levels at day 14 (38.470 × 106, 48.190 × 106, and 3.020 × 106 for groups A, B, and C, respectively). At day 14, healing was significantly better in group C compared to B (p = 0.007). Group A showed no significant differences compared to other groups.


(1) The presence of alcohol may increase the effectiveness of CHX in early wound healing, (2) C31G might be an alternative solution prescribed during early postoperative period after non-regenerative periodontal flap surgery.

Clinical relevance

The present study found that active agent C31G displayed no significant differences to CHX formulations regarding periodontal wound healing improvement and might be used alternatively after non-regenerative periodontal flap surgery. In addition, an alcohol based 0.12% CHX mouthwash was more effective than an alcohol-free 0.12% CHX and C31G mouthrinse on plaque control in the absence of mechanical oral hygiene.


Chlorhexidine Alcohol C31G Mouthrinses Early postsurgical wound healing 



The laboratory support provided by Dr. Effie C. Tsilibary (Head of Institute of Biosciences and Applications, National Center for Scientific Research “Demokritos”, Athens, Greece) and Christina Gkolfinopoulou is highly appreciated.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in human participants were in accordance with the ethical standards of Research and Ethics Committee of School of Dental Medicine, National and Kapodistrian University of Athens, Greece and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Hamp SE, Rosling B, Lindhe J (1975) Effect of chlorhexidine on gingival wound healing in the dog. A histometric study. J Clin Periodontol 2:143–152CrossRefPubMedGoogle Scholar
  2. 2.
    Powell CA, Mealey BL, Deas DE, McDonnell HT, Moritz AJ (2005) Post-surgical infections: prevalence associated with various periodontal surgical procedures. J Periodontol 76(3):329–333. CrossRefPubMedGoogle Scholar
  3. 3.
    Noguerol B, Sanz M, Follana M, Bascones A (1991) Efficacy of an ultra-soft toothbrush in the postoperative period after periodontal surgery (Spanish). Periodoncia 1:52–63Google Scholar
  4. 4.
    Brecx M, Netuschil L, Reichert B, Schreil G (1990) Efficacy of Listerine, Meridol and chlorhexidine mouthrinses on plaque, gingivitis and plaque bacteria vitality. J Clin Periodontol 17(5):292–297. CrossRefPubMedGoogle Scholar
  5. 5.
    Overholser CD, Meiller TF, DePaola LG, Minah GE, Niehaus C (1990) Comparative effects of 2 chemotherapeutic mouthrinses on the development of supragingival dental plaque and gingivitis. J Clin Periodontol 17(8):575–579. CrossRefPubMedGoogle Scholar
  6. 6.
    Charles CH, Mostler KM, Bartels LL, Mankodi SM (2004) Comparative antiplaque and antigingivitis effectiveness of a chlorhexidine and an essential oil mouthrinse: 6-month clinical trial. J Clin Periodontol 31(10):878–884. CrossRefPubMedGoogle Scholar
  7. 7.
    Loe H, Schiott CR (1970) The effect of mouthrinses and topical application of chlorhexidine on the development of dental plaque and gingivitis in man. J Periodontal Res 5(2):79–83. CrossRefPubMedGoogle Scholar
  8. 8.
    Emilson CG (1977) Susceptibility of various microorganisms to chlorhexidine. Scand J Dent Res 85(4):255–265PubMedGoogle Scholar
  9. 9.
    Wade WG, Addy M (1989) In vitro activity of a chlorhexidine-containing mouthwash against subgingival bacteria. J Periodontol 60(9):521–525. CrossRefPubMedGoogle Scholar
  10. 10.
    Denyer SP (1995) Mechanisms of action of antibacterial biocides. Int Biodeterior Biodegrad 36(3-4):227–245. CrossRefGoogle Scholar
  11. 11.
    Schiott CR, Loe H, Jensen SB, Kilian M, Davies RM, Glavind K (1970) The effect of chlorhexidine mouthrinses on the human oral flora. J Periodontal Res 5(2):84–89. CrossRefPubMedGoogle Scholar
  12. 12.
    Schiott CR, Briner WW, Loe H (1976) Two year oral use of chlorhexidine in man. II The effect on the salivary bacterial flora. J Periodontal Res 11(3):145–152CrossRefPubMedGoogle Scholar
  13. 13.
    Hase JC, Edwardsson S, Rundegren J, Attstrom R, Kelty E (1998) 6-month use of 0.2% delmopinol hydrochloride in comparison with 0.2% chlorhexidine digluconate and placebo (II). Effect on plaque and salivary microflora. J Clin Periodontol 25:841–849CrossRefPubMedGoogle Scholar
  14. 14.
    Flotra L, Gjermo P, Rolla G, Waerhaug J (1971) Side effects of chlorhexidine mouth washes. Scand J Dent Res 79(2):119–125PubMedGoogle Scholar
  15. 15.
    Van Strydonck DA, Slot DE, Van der Velden U, Van der Weijden F (2012) Effect of a chlorhexidine mouthrinse on plaque, gingival inflammation and staining in gingivitis patients: a systematic review. J Clin Periodontol 39(11):1042–1055. CrossRefPubMedGoogle Scholar
  16. 16.
    Dogan S, Gunay H, Leyhausen G, Geurtsen W (2003) Effects of low-concentrated chlorhexidine on growth of Streptococcus sobrinus and primary human gingival fibroblasts. Clin Oral Investig 7(4):212–216. CrossRefPubMedGoogle Scholar
  17. 17.
    Boisnic S, Ben Slama L, Branchet-Gumila MC, Watts M, d’Arros G (2006) Wound healing effect of Eludril in a model of human gingival mucosa (Serbian). Rev Stomatol Chir Maxillofac 107:431–435CrossRefPubMedGoogle Scholar
  18. 18.
    Ribeiro DA, Bazo AP, da Silva Franchi CA, Marques ME, Salvadori DM (2004) Chlorhexidine induces DNA damage in rat peripheral leukocytes and oral mucosal cells. J Periodontal Res 39(5):358–361. CrossRefPubMedGoogle Scholar
  19. 19.
    Eren K, Ozmeric N, Sardas S (2002) Monitoring of buccal epithelial cells by alkaline comet assay (single cell gel electrophoresis technique) in cytogenetic evaluation of chlorhexidine. Clin Oral Investig 6:150–154. CrossRefPubMedGoogle Scholar
  20. 20.
    Lamster IB, Alfano MC, Seiguer MC, Gordon JM (1983) The effect of Listerine antiseptic on reduction of existing plaque and gingivitis. Clin Prev Dent 5:12–16Google Scholar
  21. 21.
    Claffey N (2003) Essential oil mouthwashes: a key component in oral health management. J Clin Periodontol 30(Suppl. 5):22–24. CrossRefPubMedGoogle Scholar
  22. 22.
    Bolanowski SJ, Gescheider GA, Sutton SV (1995) Relationship between oral pain and ethanol concentration in mouthrinses. J Periodontal Res 30(3):192–197. CrossRefPubMedGoogle Scholar
  23. 23.
    Penugonda B, Settembrini L, Scherer W, Hittelman E, Strassler H (1994) Alcohol-containing mouthwashes: effect on composite hardness. J Clin Dent 5:60–62PubMedGoogle Scholar
  24. 24.
    Winn DM, Blot WJ, McLaughlin JK, Austin DF, Greenberg RS, Preston-Martin S, Schoenberg JB, Fraumeni JF (1991) Mouthwash use and oral conditions in the risk of oral and pharyngeal cancer. Cancer Res 51(11):3044–3047PubMedGoogle Scholar
  25. 25.
    Wynder EL, Kabat G, Rosenberg S, Levenstein M (1983) Oral cancer and mouthwash use. J Natl Cancer Inst 70(2):255–260PubMedGoogle Scholar
  26. 26.
    Lachenmeier DW, Gumbel-Mako S, Sohnius EM, Keck-Wilhelm A, Kratz E, Mildau G (2009) Salivary acetaldehyde increase due to alcohol-containing mouthwash use: a risk factor for oral cancer. Int J Cancer 125(3):730–735. CrossRefPubMedGoogle Scholar
  27. 27.
    La Vecchia C (2009) Mouthwash and oral cancer risk: an update. Oral Oncol 45(3):198–200. CrossRefPubMedGoogle Scholar
  28. 28.
    Leyes Borrajo JL, Garcia VL, Lopez CG, Rodriguez-Nunez I, Garcia FM, Gallas TM (2002) Efficacy of chlorhexidine mouthrinses with and without alcohol: a clinical study. J Periodontol 73(3):317–321. CrossRefPubMedGoogle Scholar
  29. 29.
    Lorenz K, Bruhn G, Heumann C, Netuschil L, Brecx M, Hoffmann T (2006) Effect of two new chlorhexidine mouthrinses on the development of dental plaque, gingivitis, and discolouration. A randomized, investigator-blind, placebo-controlled, 3-week experimental gingivitis study. J Clin Periodontol 33(8):561–567. CrossRefPubMedGoogle Scholar
  30. 30.
    Todkar R, Sheikh S, Byakod G, Muglikar S (2012) Efficacy of chlorhexidine mouthrinses with and without alcohol—a clinical study. Oral Health Prev Dent 10(3):291–296PubMedGoogle Scholar
  31. 31.
    Papaioannou W, Vassilopoulos S, Vrotsos I, Margaritis V, Panis VA (2016) Comparison of a new alcohol-free 0.2% chlorhexidine oral rinse to an established 0.2% chlorhexidine rinse with alcohol for the control of dental plaque accumulation. Int J Dent Hyg 14(4):272–277. CrossRefPubMedGoogle Scholar
  32. 32.
    Cortellini P, Labriola A, Zambelli R, Prato GP, Nieri M, Tonetti MS (2008) Chlorhexidine with an anti discoloration system after periodontal flap surgery: a cross-over, randomized, triple-blind clinical trial. J Clin Periodontol 35(7):614–620. CrossRefPubMedGoogle Scholar
  33. 33.
    Olsson H, Asklow B, Johansson E, Slotte C (2012) Rinsing with alcohol-free or alcohol-based chlorhexidine solutions after periodontal surgery. A double-blind, randomized, cross-over, pilot study. Swed Dent J 36(2):91–99PubMedGoogle Scholar
  34. 34.
    Corner AM, Dolan MM, Yankell SL, Malamud D (1988) C31G, a new agent for oral use with potent antimicrobial and antiadherence properties. Antimicrob Agents Chemother 32(3):350–353. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Corner AM, Brightman VJ, Cooper S, Yankell SL, Malamud D (1990) Clinical study of a C31G containing mouthrinse: effect on salivary microorganisms. J Clin Dent 2(2):34–38PubMedGoogle Scholar
  36. 36.
    Renton-Harper P, Addy M, Moran J, Doherty FM, Newcombe RG (1996) A comparison of chlorhexidine, cetylpyridinium chloride, triclosan, and C31G mouthrinse products for plaque inhibition. J Periodontol 67(5):486–489. CrossRefPubMedGoogle Scholar
  37. 37.
    Armitage GC (1999) Development of a classification system for periodontal diseases and conditions. Ann Periodontol 4(1):1–6. CrossRefPubMedGoogle Scholar
  38. 38.
    Miller SC (1950) Textbook of Periodontia, 3rd edn. The Blakeston Co., Philadelphia, p 125Google Scholar
  39. 39.
    Hamp SE, Nyman S, Lindhe J (1975) Periodontal treatment of multirooted teeth: results after 5 years. J Clin Periodontol 2:126–135CrossRefPubMedGoogle Scholar
  40. 40.
    O'Leary TJ, Drake RB, Naylor JE (1972) The plaque control record. J Periodontol 43(1):38. CrossRefPubMedGoogle Scholar
  41. 41.
    Ainamo J, Bay I (1975) Problems and proposals for recording gingivitis and plaque. Int Dent J 25(4):229–235PubMedGoogle Scholar
  42. 42.
    Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ et al (2010) CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. J Clin Epidemiol 63(8):e1–37. CrossRefPubMedGoogle Scholar
  43. 43.
    Cortellini P, Prato GP, Tonetti MS (1995) The modified papilla preservation technique. A new surgical approach for interproximal regenerative procedures. J Periodontol 66(4):261–266. CrossRefPubMedGoogle Scholar
  44. 44.
    Cortellini P, Prato GP, Tonetti MS (1999) The simplified papilla preservation flap. A novel surgical approach for the management of soft tissues in regenerative procedures. Int J Periodontics Restorative Dent 19(6):589–599PubMedGoogle Scholar
  45. 45.
    Wachtel H, Schenk G, Bohm S, Weng D, Zuhr O, Hurzeler MB (2003) Microsurgical access flap and enamel matrix derivative for the treatment of periodontal intrabony defects: a controlled clinical study. J Clin Periodontol 30(6):496–504. CrossRefPubMedGoogle Scholar
  46. 46.
    Silness J, Loe H (1964) Periodontal disease in pregnancy. II. Correlation between oral hygiene and periodontal condition. Acta Odontol Scand 22(1):121–135. CrossRefPubMedGoogle Scholar
  47. 47.
    Sagel PA, Lapujade PG, Miller JM, Sunberg RJ (2000) Objective quantification of plaque using digital image analysis. Monogr Oral Sci 17:130–143. CrossRefPubMedGoogle Scholar
  48. 48.
    Laugisch O, Ramseier CA, Salvi GE, Hägi TT, Bürgin W, Eick S, Sculean A (2016) Effects of two different post-surgical protocols including either 0.05% chlorhexidine herbal extract or 0.1% chlorhexidine on post-surgical plaque control, early wound healing and patient acceptance following standard periodontal surgery and implant placement. Clin Oral Investig 20(8):2175–2183. CrossRefPubMedGoogle Scholar
  49. 49.
    Nadkarni MA, Martin FE, Jacques NA, Hunter N (2002) Determination of bacterial load by real-time PCR using a broad-range (universal) probe and primers set. Microbiology 148(1):257–266. CrossRefPubMedGoogle Scholar
  50. 50.
    Dastoor SF, Travan S, Neiva RF, Rayburn LA, Giannobile WV, Wang HL (2007) Effect of adjunctive systemic azithromycin with periodontal surgery in the treatment of chronic periodontitis in smokers: a pilot study. J Periodontol 78(10):1887–1896. CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Kumar P, Rattan V, Rai S (2015) Comparative evaluation of healing after gingivectomy with electrocautery and laser. J Oral Biol Craniofacial Res 5:69–74CrossRefGoogle Scholar
  52. 52.
    Poggi P, Rodriguez y Baena R, Rizzo S, Rota MT (2003) Mouthrinses with alcohol: cytotoxic effects on human gingival fibroblasts in vitro. J Periodontol 74(5):623–629. CrossRefPubMedGoogle Scholar
  53. 53.
    Furuichi Y, Lindhe J, Ramberg P, Volpe AR (1992) Patterns of de novo plaque formation in the human dentition. J Clin Periodontol 19(6):423–433. CrossRefPubMedGoogle Scholar
  54. 54.
    Caton JG, Blieden TM, Eowenguth RA, Erantz BJ, Wagener CJ, Dohlin JM, Stein SH, Proskin HM (1993) Comparison between mechanical cleaning and an antimicrobial rinse for the treatment and prevention of interdental gingivitis. J Clin Periodontol 20(3):172–178. CrossRefPubMedGoogle Scholar
  55. 55.
    Bergstrom J (1981) Short-term investigation on the influence of cigarette smoking upon plaque accumulation. Scand J Dent Res 89(3):235–238PubMedGoogle Scholar
  56. 56.
    Chen X, Wolff L, Aeppli D, Guo Z, Luan W-M, Baelum V, Fejeskov O (2001) Cigarette smoking, salivary/gingival crevicular fluid cotinine and periodontal status. A 10-year longitudinal study. J Clin Periodontol 28:331–339CrossRefPubMedGoogle Scholar
  57. 57.
    Salvi GE, Ramseier CA, Kandylaki M, Sigrist L, Awedowa E, Lang NP (2005) Experimental gingivitis in cigarette smokers. A clinical and microbiological study. J Clin Periodontol 32(5):441–447. CrossRefPubMedGoogle Scholar
  58. 58.
    Diaz PI, Chalmers NI, Rickard AH, Kong C, Milburn CL, Palmer RJ, Kolenbrander PE (2006) Molecular characterization of subject-specific oral microflora during initial colonization of enamel. Appl Environ Microbiol 72(4):2837–2848. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Anastasios M. Gkatzonis
    • 1
    Email author
  • Spyridon I. Vassilopoulos
    • 1
  • Ioannis K. Karoussis
    • 1
  • Archontia Kaminari
    • 2
  • Phoebus N. Madianos
    • 1
  • Ioannis A. Vrotsos
    • 1
  1. 1.Department of Periodontology, School of Dental MedicineNational and Kapodistrian University of AthensAthensGreece
  2. 2.Institute of Biosciences and ApplicationsNational Center for Scientific Research “Demokritos”AthensGreece

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