Promotion Promotion Promotion
Welcome to Win12u about us product education testimonials Clinical Results Contact

The Efficacy Of An Alcohol-Free 0.12% w/v Chlorhexidine Gluconate Mouthrinse (Oradex)
UMA.S*, Dasan Swaminathan, Faculty of Dentistry, University of Malaya, Kuala Lumpur

Abstract

Chlorhexidine gluconate, a dicationic bisbiguanide agent, contains anti-plaque properties and has undergone thorough research in the past few decades. Most chlorhexidine gluconate mouthrinses presently available contain alcohol in varying concentrations. The role of alcohol in these mouthrinses is to act as a preservative and solvent although it may have deleterious effects on the oral epithelium on long term usage. Recently, a locally produces alcohol-free 0.12% w/v alcohol-free chlorhexidine gluconate mouthrinse (Oradex has become available in Malaysia. This double-blind, cross-over, placebo controlled clinical study was aimed at determining the effect of this alcohol-free product compared to a placebo without the active ingredient chlorhexidine gluconate. A group of 60 meticulously screened subjects were assigned into two groups of 30 each. The first group started using the test product for 2 weeks followed by a washout period of 4 weeks. After this duration, this group used the placebo for a further 2 weeks. The 2nd group underwent similar protocol as the 1st except that this group started with the placebo. Measurements consisting of the following scores were recorded at baseline and after 2 weeks for each group: Plaque (Quigley-Hein with Turesky Modification Index); Gingivitis (Loe & Silness Index); Papillary bleeding (Saxer & Muhlemann Index); Stain (Shaw & Murray Index) and Calculus (Volpe-Manhold Index). Full mouth prophylaxis was carried out for all subjects after measurements at baseline as well as after the 2-week period. Each subject was provided with a standard toothbrush and toothpaste and instructed to continue with their routine, unsupervised oral hygiene. They were told to rinse with 15ml of the designated mouthrinse twice daily for 30s each after toothbrushing. The results of this study indicated that there was significant improvement in the plaque (p<0.05), gingival (p<0.05) and papilla bleeding (p<0.05) scores compared to the placebo, which was anticipated with this dicationic anti-plaque agent. The results of this study was comparable to several other studies on chlorhexidine gluconate mouthrinses of similar concentrations and containing alcohol. In conclusion, this clinical study showed that this alcohol-free 0.12% w/v chlorhexidine gluconate mouthrinse is effective in reducing plaque and gingivitis but causes staining and calculus formation. (a result of dead bacteria becoming calcified)

Introduction

Dental plaque accumulation is the prerequisite for the development of gingivitis (Löe et al. 1965). Current opinion favours the concept that plaque-induced gingivitis always precedes periodontitis (Löe 1986 and Lindhe 1986) although not all gingivitis proceeds to periodontitis (Newman 1987).
Indeed, the long-term success of periodontal treatment is dependent on satisfactory oral hygiene practices by individuals to maintain plaque level compatible with gingival health (Axelsson and Lindhe 1981 a,b). Periodontal treatment is also directed towards eliminating subgingival plaque which itself is derived from supragingival plaque (Lindhe 1999).
Supragingival plaque control is largely the responsibility of the individual, using toothbrushes and interdental cleaning devices (Axelsson 1994) and remains the most widely accepted method of oral disease prevention (Hancock 1996). Chemical agents have increasingly been used as adjuncts to mechanical plaque control. They are intended to augment, and not to replace, mechanical plaque control (Ciantar 1995). Given the microbial nature of plaque, antimicrobial agents such as chlorhexidine have thus far been the mainstay of chemical plaque control and have been used in the prevention and treatment of gingivitis and periodontitis (Addy 1986; Slots & Rams 1990; Wennstrom 1992: Addy et al. 1994; Goodson 1994 and Addy & Renton-Harper 1996). Most chlorhexidine mouthrinses available in the market today contain alcohol in variable concentrations. Concerns over the possible association of alcohol intake and oral and pharyngeal cancer have been extended to include alcohol-containing mouthrinses, although the scientific validity of these concerns has not been established to date (Lindhe 1999).

Aim of the Study

To ascertain the effects of an alcohol-free chlorhexidine mouthrinse (Oradex) on plaque, gingivitis, papilla bleeding, stain and calculus status of patients compared to a placebo.

Literature review

Dental plaque occupies a central role as the major aetiological factor in the pathogenesis of dental caries and periodontal disease (Löe et al. 1965, Theilade et al. 1966 and Von Der Fehr et al. 1970). The conceptual framework for these oral diseases, like other infectious diseases, is that of a balance between host response on the one hand and microbial pathogeneses on the other. In health, host immune responses are sufficient to hold in check the pathogenic potential of both the normal resident microbial flora or exogenous microbial pathogens (Shibly et al. 1995). Infectious diseases such as dental caries and periodontal disease occur when this equilibrium is disturbed (Hardie 1992). Consequently, these two diseases may be prevented or successfully controlled by the complete, regular removal of plaque from tooth surfaces (Seymour et al. 1992).

Rationale for chemical supragingival plaque control

Periodontal disease is global in distribution and as such, control of the disease in all its forms must cross all socioeconomic barriers (Moran 1997).
In some countries, virtually 100% of the population is effected to some degree by gingivitis at some time (Addy et al. 1986). For more severe periodontal disease in which tooth longevity is at risk, prevalence figures of approximately 5-15% of the population have been quoted and this is much higher than some other diseases (Pilot & Miyazaki 1991 and Löe et al. 1986).
It is widely accepted that the cornerstone for prevention of periodontal disease is that of prevention and/or removal of dental plaque and inhibition of gingivitis and therefore the occurrence or recurrence of periodontitis (Lindhe 1999). Research shows that the time spent on the toothbrushing procedure and the frequency of toothbrushing are key factors in determining the efficiency of supragingival plaque removal (Cummins 1997). In addition, patient dexterity, motivation and awareness of the benefits of good oral hygiene are important (Hodges et al. 1991; De Vore et al. 1990 and Lang et al. 1973). However, the dedication and motivation required to achieve or maintain such control is not the norm for most individuals (Cummins & Creeth 1992). A typical response to prophylaxis, toothbrushing instructions and motivation is a temporary improvement in gingival health, which is lost in the absence of further motivation (Svatun et al. 1990 and Stephens et al. 1990). Furthermore, population surveys suggest that high proportions of adults is affected by early periodontal disease (Burt et al. 1996 and Miller et al. 1987) suggesting that mechanical plaque control is insufficient to ensure periodontal health in most individuals.
These observations have provided a compelling rationale for the introduction of chemical agents as adjuncts to mechanical oral hygiene procedures (Kornman 1986; Newman 1986; Mandell 1988 and Van der Ouederra 1991) to control supragingival plaque formation (Cummins 1997). Indeed, antimicrobial therapy has today become established as a part of the armamentaria for the reduction of plaque and gingivitis (Jeffcoat et al. 2000).

Alcohol in Mouthrinses

Mouthrinses have been available for a long time and with the recent proliferation of varieties, their mass marketing and their sale to the general public without restriction has led to substantially increased use. With this increased usage, the monitoring and assessment of any potential adverse effects is paramount, no matter how insignificant they may seem. One of the features of mouthrinses that is of concern to dental public health workers and which could lead to oral tissue damage, is their alcohol (ethanol) content (Bhatti et al. 1994).
The amount alcohol in some mouthrinses equaled or exceeded that contained in many alcoholic beverages and if used over a long term could be a contributory factor in oral cancer (Walsh 1996). Alcohol (ethanol) within the mouthwash may cause dissolution of enamel.

CHLORHEXIDINE

The dental profession has used chlorhexidine for more than two decades and it is recognized as the primary agent for chemical plaque control (Jones 1997). Chlorhexidine is a dicationic chlorophenyl biguanide with outstanding bacteriostatic properties (Seymour & Heasman 1992). The drug was synthesized and first reported by Imperial Chemical Industries, England in 1954, following extensive investigations of the biological properties of polydiguanide compounds (Davies et al. 1954). Chlorhexidine is well-tolerated and long-lasting antiseptic which is not neutralized by body fluids or other organic compounds (Snyder & Finch 1982) and this compound was introduced for medical use in 1953 as an antiseptic cream for wounds. Its later applications included those of a presurgical skin cleanser, a surgical scrub, an obstetric cream and an instrument sterilization fluid (Seymour & Heasman 1992). The application of chlorhexidine as an antiplaque agent was suggested by Schroeder in 1969. Most of the chlorhexidine mouthrinses available in the market today contain alcohol (mainly ethanol) in varying concentrations. There are several reports of the ill effects of alcohol on the oral tissue although there is little scientific proof of this.

Materials and Methods

A group of 60 subjects (48 females, 12 males; age range 22 to 46 years), were recruited from the staff of the University Hospital. Prior to their participation, they were meticulously screened to ascertain if they conformed with the criteria for the study. They were given written and verbal explanation and instructions pertaining to the study. Consent forms were signed by all participants.
The trial design was a placebo-controlled, double-blind, crossover type consisting of two 14-day test periods separated by a washout period of 4 weeks. During the entire study the participants continued to exercise their regular non-supervised, self-performed oral hygiene measures. They were each provided with a toothbrush (Oral B) and toothpaste (Oral B).
The participants were assigned into two groups, those receiving the mouthrinses in the order active/placebo(Group A0 and those in the order placebo/active(Group B). The mouthrinses were dispensed through a staff of the Department who held a sealed code-breaker. Due to the double-blind design, all solutions had the same colour and were kept in the same kind of bottle.

Clinical measurements

Plaque Scores

Assessment was done after disclosing the supragingival plaque with erythrosine dye. Four surfaces (mesiobuccal, mesiolingual, distobuccal and distolingual) on four teeth (incisor, canine, premolar and molar) in each quadrant were scored according to the criteria of the Turesky et al.(1970) modification of the Quigley and Hein (1963) plaque index.

Gingivitis Scores

Gingivitis was scored on four surfaces (mesiobuccal, mesiolingual, distobuccal and distolingual) of four teeth (incisor, canine, premolar and molar) in each quadrant according to the criteria of Loe and Silness (1963).

Papillary Bleeding Scores

The interdental papilla of four teeth (incisor, canine, premolar and molar) in each quadrant were scored following gentle probing according to the criteria of Saxer & Muhlemann (1975).

Calculus Scores

Scoring was done on the lingual surfaces of the lower anterior teeth according to the criteria of the Vlope-Mabhold Index (1965). The greatest area of calculus is measured in millimeters using a periodontal probe through the mesio-incisal and disto-incisal angles of the teeth.

Stain Scores

The Shaw and Murray Index (1977) was used to score stain on four surfaces of four teeth in each quadrant.

Methodology

Pre-treatment phase

All subjects were rendered prophylaxis prior to commencement of the study. This was because some of the subjects had dental check-up with scaling done only recently whereas some others had not had scaling for the past few years. A period of four weeks was then allowed to elapse before the first test period to obtain more standardized levels of oral hygiene.

First test period

Baseline measurements of plaque, gingivitis, papillary bleeding, calculus and stain were recorded. Plaque was scored the last after disclosing it with erythrosine dye. This was followed by ultrasonic scaling and polishing of all teeth with a rubber cup and prophylaxis paste.
The subjects were each given a new medium-soft toothbrush (Oral B) and a tube of toothpaste (Oral B). They were instructed to continue with their routine toothbrushing methods. The designated mouthrinses were dispensed according to the groups of the subjects. Group A started with the active product whereas Group B with the placebo. They were instructed to rinse twice daily about 30 minutes after toothbrushing with 15ml of the solution for 60 seconds, followed by expectoration of residual mouthrinse. On day 14, all subjects returned for clinical measurements. This was followed by scaling and polishing of all teeth.

Washout period

An interval of four weeks was given after the first test period so that the effects from the previous mouthrinse did not carry over into the next test period. During the washout period the subjects exercised toothbrushing as they are used to but refrained from using any mouthrinse.

Second test period

The baseline measurements were repeated and followed by prophylaxis. The subjects were allotted the alternative mouthrinse and instructed to use is exactly as they did the previous product. They returned two weeks later for clinical measurements. All the subjects were then offered full-mouth prophylaxis.

Results

All subjects satisfactorily completed both rinsing regiments and presented for examination on the respective days. All data were analysed using Pearsons chi-square test with the SPSS version 9.0 programme.

1. Plaque Score

Higher percentage of subjects were found to have improved plaque status when they rinsed with chlorhexidine compared to placebo (71.7% Vs 35%). The difference was found to be statistically significant (p<0.05). (Table 1.)

 

Type of Mouthrinse

Effect

Total

Effective

Not Effective

Chlorhexidine

Count

43

17

60

Percentage

71.7%

28.3%

100.0%

Placebo

Count

21

39

60

Percentage

35%

65%

100.0%

                                                                                            Table 1

2. Gingivitis Score 

Higher percentage of subjects exhibited improved gingival status when they rinsed with chlorhexidine compared to placebo (85% Vs 28.3%). The difference was found to be statistically significant (p<0.05). (Table 2)

Type of Mouthrinse

Effect

Total

Effective

Not Effective

Chlorhexidine

Count

51

9

60

Percentage

85.0%

15.0%

100.0%

Placebo

Count

17

43

60

Percentage

28.3%

71.1%

100.0%

                                                                                       Table 2

3. Papilla Bleeding Score 
Higher percentage of patients had improved papilla bleeding status when they rinsed with chlorhexidine compared with placebo (90% Vs 45%). The difference was found to be statistically significant (p<0.05). 
(Table 3)

Type of Mouthrinse

Effect

Total

Effective

Not Effective

Chlorhexidine

Count

54

6

60

Percentage

90.0%

10.0%

100.0%

Placebo

Count

27

33

60

Percentage

45.0%

55.0%

100.0%

                                                                                    Table 3

4. Calculus Score 
Higher percentage of subjects exhibited increased calculus deposition when they rinsed with chlorhexidine compared to the placebo (86.7% Vs 23.3%). The difference was found to be statistically significant (p<0.05). (Table 4).

Type of Mouthrinse

Effect

Total

Effective

Not Effective

Chlorhexidine

Count

52

8

60

Percentage

86.7%

13.3%

100.0%

Placebo

Count

14

46

60

Percentage

23.3%

76.7%

100.0%

                                                                                      Table 4

5. Stain Score 
Higher percentage of subjects had increased stain formation when rinsing with chlorhexidine compared to the placebo (95% Vs 18.3%). The difference was found to be statistically significant (p<0.05). (Table 5)

Type of Mouthrinse

Effect

Total

Effective

Not Effective

Chlorhexidine

Count

57

3

60

Percentage

95.0%

5.0%

100.0%

Placebo

Count

11

49

60

Percentage

18.3%

81.7%

100.0%

                                                                                  Table 5

Discussion

Mouthrinses have been available for a long time and with the recent proliferation of varieties, their mass marketing and their sale to the public without restriction has led to substantially increased use. With this increased usage, the monitoring and assessment of any potential adverse effect is paramount, no matter how insignificant they may seem. One of the features of mouthrinses that is of concern to dental public health workers and which could lead to oral tissue damage is their alcohol content (Bhatti et al. 1994). The concept of alcohol-free mouthrinses is relatively new (Eldridge et al. 1998). The findings of this study is similar with those of the only other clinical study done on alcohol-free chlorexidine mouthrinse by Eldridge et al. (1998) which concluded that alcohol-free chlorhexidine mouthrinse was effective in reducing plaque and gingivitis. The results of the present study were also similar to several other studies done on alcohol-containing 0.12% chlorhexidine mouthrinses which concluded that 15ml of 0.12% chlorhexidine mouthrinse was significantly clinically better than a placebo when used alongside toothbrushing.

Conclusion

In conclusion, this alcohol-free product is effective in improving plaque, gingivitis papilla bleeding but causes calculus and stain formation in comparison to the placebo. The formation of calculus is a result of the presence of dead bacteria becoming calcified because of the excellent antibacterial properties of chlorhexidine.
The results of this study indicate that alcohol-free chlorhexidine mouthrinses are worthy of further clinical investigation. This would be particulary useful to individuals who are averse to alcohol.

REFERENCES

1. Addy M & Renton-Harper P (1996). Local and systemic chemotheraphy in the management of periodontal disease: an opinion and review of the concept. J of Oral Rehabilitation 1996; 23: 219-231.
2. Addy M Chlorhexidine compared with other locally delivered anti-microbials. A short review. Journal of Clin Periodontol 1986; 13: 957-964.
3. Addy M, Dummer PMH, Griffiths G, Hicks R, Kingdon A, Shaw WC. Prevalence of plaque, gingivitis and caries in 11-12 year olds in South Wales. Community Dent Oral Epidemiol 1986; 14: 115-118.
4. Addy M, Moran J and Wade W. Chemical plaque control in the prevention of gingivitis and periodontitis. In: Lang, N.P. & Karring T, eds. Proceedings of the 1st European Workshop on Periodontology. London : Quintessence Publishing 1994; pp.244-257.
5. Axelsson P & Lindle J. Effect of controlled oral hygiene procedures on caries and periodontal disease in adults. Results after 6 yrs. J of Clin Periodontol 1981a; 8: 239-248.
6. Axelsson P & Lindhe J. The significance of maintenance care in the treatment of periodontal disease. J of Clin Periodontol 1981b; 8: 281-294.
7. Axelsson P. Mechanical plaque control. In : Lang, N.P. & Karring T, eds. Proceedings of the 1st European Workshop on Periodontology. London : Quintessence Publishing 1994, pp.219-243.
8. Bhatti SA, Walsh TF and Douglas CIW. Ethanol and pH levels of proprietary mouthrinses. Community Dental Health 1994; 11: 71-74.
9. Burt BA, Armitage GC, Cochran DL, Cohen RC, Greenstein G, Mariotti D, Rethman MP, Somerman MP, Van Dyke TE, Dennison DK, Genco RJ, Hanes DK, Page RC, Rees TD and Young WL. Epidemiology of periodontal diseases. J Periodontol 1996; 67: 935-945.
10. Ciantar M. Chemical agents in Periodontal Theraphy : Use or Misuse? Dental Update 1995 July/August; 238-241.
11. Cummins D & Creeth JE. Delivery of Antiplaque Agents from Dentifrices, Gels and Mouthwashes. J Dent Res 1992; 7: 1439-1449.
12. Cummins D. Vehicles: How to deliver the goods. Periodontology 2000 1997;15:84-99.
13. Davies GE, Francis J and Martin AR. 1:6-di-4' clorophenyl-diguanido-hexane ('Hibitane'):laboratory investigation of a new antibacterial agent of high potency. British Journal of Pharmacology 1954; 9: 192-196.
14. De Vore CH, Beck FM and Horton JE. Plaque score changes based primarily on patient performance at specific time intervals. J of Periodontol 1990; 61: 343-346.
15. Goodson JM. Antimicrobial strategies for treatment of periodontal diseases. Periodontology 2000 1994;5: 142-168.
16. Hancock EB. Prevention. Proceedings of the 1996 World Workshop in Periodontitis. Annals Periodontol 1996; 1: 223-255.
17. Hardie JM. Oral microbiology: current concepts in the microbiology of dental caries and periodontal disease. Br Dent J 1992; 172: 271-278.
18. Hodges CA, Branco JG and Cancro LP. Dental plaque under timed intervals of toothbrushing. J Dent Res 1991; 60: 425.
19. Jeffcoat MK, Palcanis KG, Weatherford TW, Reese M, Geurs NC and Flashner M. Use of a Biodegradable Chlorhexidine chip in the treatment of Adult Periodontitis: Chemical and Radiograhic findings. J of Periodontol 2000; 71: 256-262.
20. Jones CG. Chlorhexidine : is it still the gold standard? Periodontology 2000 1997; Vol. 15: 55-62.
21. Kornman KS. The role of supragingival plaque in the prevention and treatment of periodontal disease. A review of current concepts. J Periodontal Res 1986; 16(suppl): 5-22.
22. Lang NP, Cumming BR and Loe H. Toothbrushing frequency as it relates to plaque development and gingival health. J of Periodontol 1973; 44: 396-405.
23. Lindhe J. In : Gingivitis, General Discussion. J of Clin Periodontal 1986; 13:395.
24. Lindhe J. Clinical Periodontology and Implant Dentistry. Third Ed. Munksgaard 1999 pp. 461-487.
25. Loe H, Progression of natural untreated periodontal disease in man. In : Borderland between Caries and Periodontal Disease 1986, 3rd edn. Geneve : Medecin et Hygiene.
26. Loe H, Theilade E and Jensen S. Experimental gingivitis in man. J Periodontol 1965; 36: 177-187.
27. Mandel ID. Chemotherapeutic aspects for controlling plaque and gingivitis. J Clin Periodontol 1988; 15: 488-498.
28. Miller AJ, Brunelle JA, Carlos JP, Brown LJ and Loe H. Oral health of United States adults. National findings. The national survey of oral health in US employed adults and seniors (1985-1986). Washington DC:NIH (Publication 87-2868).
29. Moran J. Chemical plaque control : prevention for the masses. Periodontology 2000 1997; 15: 109-117.
30. Newman M. Oral microbiology with emphasis on etiology. In : perspectives on oral microbial therapeutics. Littleton, MA 1987 : PSG Publishing: 1-24.
31. Pilot T & Miyazaki H. Periodontal conditions in Europe. J Clin Periodontol 1991; 18: 353-357.
32. Schroeder HE. Formation and inhibition of dental calculus, 1969; p. 129. Hans Huber. Stuttgart.
33. Seymour RA & Heasman PA. Anti plaque and anti calculus agents. In: Drugs, Diseases and the Periodontium 1992, pp 153-179, New York, Oxford University Press.
34. Shibly O, Rifai S and Zambon JJ. Supragingival dental plaque in the etiology of oral diseases. Periodontology 2000 1995; Vol.8: 42-59.
35. Slots J & Rams TE. Antibiotics in periodontal theraphy : advantages and disadvantages. J of Clin Periodontol 1990; 17 : 479-493.
36. Snyder IS & Finch RG. Antiseptics, disinfectants and sterilization. In Modern Pharmacology (ed. CR Craig and RE Stitzel) 1982, p. 743. Little, Brown & Co., Boston.
37. Svatun B, Gjermo P, Eriksen M and Rolla G (1990). A comparison of plaque inhibiting activity of stannous fluoride and chlorhexidine. Acta Odontol Scand 1990; 35: 247-250.
38. Theilade E, Wright WH, Jensen SB and Loe H. Experimental gingivitis in man. II. A longitudinal clinical and bacteriological investigation. J of Periodontal Res 1966; 1:1-13.
39. Van der Ouderaa FJG. Antiplaque agents. Rationale and prospects for prevention of gingivitis and periodontal disease. J Clin Periodontol 1991; 18:447-454.
40. Von Der Fehr FR, Loe H and Theilade E (1970). Experimental caries in man. Caries Research 1970; 4: 131-148