Comparing the Effect of 0.06%, 0.12% and 0.2% Chlorhexidine on Plaque, Bleeding and Side Effects in an Experimental Gingivitis Model

A Parallel Group, Double Masked Randomized Clinical Trial

Maliha Haydari; Ayse Gul Bardakci; Odd Carsten Koldsland; Anne Merete Aass; Leiv Sandvik; Hans R. Preus

Disclosures

BMC Oral Health. 2017;17(118) 

In This Article

Discussion

The findings of the present study showed that CHX 0.2% proved statistically significantly better than 0.12% and 0.06% CHX in preventing supragingival plaque on the participants' teeth after 21 days when applying the plaque score of Løe and Silness.[12] Moreover, between them, the 0.06% and 0.12% CHX products showed no statistical significant difference in plaque inhibition with any of the plaque indices.[11,12] No statistically significant differences in gingival index between the groups were found after 3 weeks rinsing with the 3 different CHX solutions.

The finding of no significant difference in gingival index scores between the three mouthwashes, despite significant difference in plaque scores between the 0.2% and the 0.12%/0.06% concentrations warrants a discussion. No human is free of slight gingival inflammation, and most adults have a GI of approximately 1 following regular tooth cleaning. The average GI for quadrant 1 (rinsing only) after 3 weeks in group 1, 2 and 3 respectively were all 1.1 (all sites combined), and 1.2 (only approximal surfaces). These were in concert with findings following the "the non-cleansing period", i.e. no chemical or mechanical plaque preventing procedures from the original experiment by Löe et al.[13] where the GI of maxillary premolars and molars were 1.01 and 1.1 respectively. Testing CHX 0.2% in a group of soldiers, Fløtra et al. 1972[17] showed that average GI score was a little shy of 1 in the experimental group after 8 weeks whereas the plaque index was 0.8, the latter being in the range of observations from the present study. Fløtra et al.[17] used a laboratory produced CHX solution, whereas the present study tested the commercial products, and this may have had an impact on the effect of the CHX on plaque as well as the gingivitis (for discussion - see below).

CHX 0.12% and 0.2% mouthwashes are both recommended for short-term use, and for medicinal purposes, classifying the products as medical products. CHX 0.06%, recommended for long-term use, is intended to be a supplement to daily tooth cleaning/brushing and is therefore classified amongst the cosmetic and toiletry product lines with a market strategy aimed at preventing dental plaque at a population level. Gingivitis is the result of prolonged tissue-exposure to supragingival plaque,[18] and even if the 0.06% CHX did not produce significantly more gingivitis than the 0.12% and the 0.2% CHX after 3 weeks, a remaining long standing plaque index of 1 will induce gingivitis in the long run.[13,17,18] This brings to the discussion a much more serious problem. A low-concentrate biocide like CHX is bringing a potential danger for resistance development in oral bacteria – but even more so – in the sewage microbiome. The increased use of CHX in oral and general health care[19–28] is today a clear and present danger for resistance development against this versatile antiseptic. The overall risk for acquired resistance to biocidal agents, such as CHX, is still considered to be small, provided the antiseptics are being used with care and in correct situations.[29,30] However, several outbreaks have been reported associated with contaminated CHX solutions[31] which demonstrate the ability of bacteria to adapt to CHX.[32] Therefore, future research carries with it the obligation to explore the bacterial resistance development against CHX, and not only in the oral cavity. The sewage microbiome, influenced by the increasing influx of low concentrate CHX, will eventually and inevitably produce more CHX resistant bacteria that will transcolonize humans and their microbiomes.

Few studies have compared different CHX products.[33–39] However, a systematic review and meta-analysis[9] comparing studies on 0.2% and 0.12% CHX concluded: a "small but significant difference in favor of 0.2% CHX, but that the clinical relevance of this difference was probably negligible". These studies, all but one, used Quigley and Hine plaque index (11), or the Turesky modification[11] to score the presence of plaque after the prescribed use of the tested CHX compounds. The Quigley and Hine, Turesky[11] modification index requires plaque disclosing solution, which precludes the registration between baseline and endpoint in case the participants should not brush their teeth in the meantime. Therefore, the present study was only registering the plaque and gingivitis indices at baseline and at termination of the study. Both this index (12) and the plaque and gingivitis index of Løe and Silness[12] were used for comparison to previous studies. A possible explanation for the results conveyed here being different from those previously published[9,33–39] may be that this plaque index[11] also register some of the protein coating that retains the plaque disclosing solution and that it is difficult to distinguish and set a correct score, whereas the Løe and Silness plaque index[12] detects the plaque accumulation along the gingival margin. This notion was supported by the high standard deviation (sd.) found when registering the Quigley and Hine scores in quadrant 1 (Table 2), where plaque was abundant. The sd. was more in the normal range – but still almost doubled those of Løe and Silness' - when registering Quigley and Hine scores in quadrant 2 where plaque was reduced considerably by brushing (Table 2). In studying the effect on gingivitis and periodontal diseases it would suffice to score the plaque deposits along the gingival margin as with the Løe and Silness plaque index[12] and the coronal spread of bacteria on the tooth surface does not seem that relevant.

In the present study only the commercial CHX products were compared, and no comparison to rinsing with a negative control, like water, saline or placebo solution was performed. The decision not to use a placebo solution was based on the fact that it would be impossible to make since the taste, smell, color and osmolality are different for the three mouthwashes. Also, the study was designed to compare 2 relatively new mouthwashes (0.12% and 0.06% CHX) on the Norwegian market against the well documented effect of the positive control - the 0.2% CHX mouthwash. Therefore, testing against a negative control as water seemed unnecessary. However, recently Preus and coworkers (Unpublished Observations; HR Preus) compared a commercially available essential oil product against sterile water in the same model, the same scoring crew and population of students as in the present study. In the present study the group rinsing with 0.06% CHX showed an average plaque score of all surfaces of 0.93 ± 0.41, which is almost half of the result of the average score, 1.7 ± 0.42, found when rinsing only with water in the former study (Unpublished Observations; HR Preus). Although the results cannot be compared directly, because they were not obtained in the same persons at the same time, it should be emphasized that in the present study the groups rinsing with CHX 0.12% and 0.06% presented with a much lower plaque score than those rinsing with water in the above mentioned, previous study (Unpublished Observations; HR Preus).

Another finding was that the commercially available 0.2% CHX mouthwash showed an average score of 0.65 ± 0.42 in the present study, being double the plaque score of what a 0.2% CHX solution produced (0.3 ± 0.2) in another comparable population and study of Preus et al.[15] The explanation may be that in the present study the 0.2% CHX group rinsed with a commercial product, while Preus et al.[15] used a laboratory produced rinsing solution of 0.2% CHX-glukonat with 7% alcohol and 0.2% NaF in water. The reason for the self-made CHX solution proving that much better should be investigated further, but one hypothesis may be that that the 7% alcohol, which was an ingredient in the previous formulation of Corsodyl 0.2% CHX prior to 2012, may add that much to the plaque preventing effect of the product. Another may be that the added color, taste and flavor, which were not added to the laboratory produced mouthwash, may reduce the effect of the CHX in the commercial product. Regarding the known ingredient NaF, in the 0.12 and 0.06% CHX mouthwashes, it has been shown[40] that it does not reduce the effect of the CHX, at least not in dentifrices. Moreover, 0.091% NaF (in 0.12% CHX mouthwash) and 0.025% NaF (in 0.06% CHX mouthwash) is regarded as too low concentration for sufficiently preventive effect on caries.[41]

There are suggestions by clinicians that lower concentrations of CHX in products may be compensated by increasing rinsing volume. In this study all the test subjects rinsed with 10 ml regardless of which product they tested. When one uses a plaque preventing rinse, it is not so much the product concentration that is interesting; it is the number of active molecules available for plaque prevention that is of the essence. Therefore, it would be wrong to compare the three products, with different concentrations, but at the same time make more of the active ingredient available by increasing the rinsing volume in the lower concentration products (0.12% and 0.06% CHX). Therefore, to perform a just comparison, they all rinsed with 10 ml of product, regardless of CHX concentration.

Among the self-reported side-effects, "loss of taste"/"taste perturbation" and "numb feeling" were the most common complaints, and the number of participants complaining about "loss of taste" was statistically significantly higher in the 0.2% CHX group than in those of 0.12% and 0.06% CHX groups. This is in concert with previous studies but in opposition to others (10).

In quadrant 2 (brushing + CHX), the plaque index remained low in all groups, suggesting that tooth brushing is sufficient to keep plaque and gingivitis scores sufficiently low to prevent gingivitis, which is in agreement with other studies.[15,41,42] Thus, sufficient oral hygiene for prevention of oral plaque-related diseases could easily be achieved without the help of daily antibacterial mouth rinses.

The subjects in the present study were dental hygienist, dental and medical students. One may therefore assume that they can present with a better oral hygiene than the layman. However, by comparing Q1 with mouth guard and Q2 without mouthguard in the same subjects, possible distinction from the general population was eliminated. The population in the study did not use tobacco of any kind, thus staining or masked gingival inflammation or keratinization due to tobacco did not influence on the results.

The research team was masked to the group allocation. Although both the commercial products 0.06% and 0.12% was fairly new to the market, some of the students might themselves have known the products by recognizing taste, especially those who rinsed with the commercially available 0.2% CHX mouthwash. To investigate a possible recognition effect among the participants they were asked at day 7, 14 and 21 if they had recognized the taste and knew which rinsing compound they were assigned to, and no guessing. The results of this showed that only a couple reported to recognize the compound they were rinsing with, which is not surprising since most of these young students never had been exposed to either of the commercial products tested. Thus, the study should be regarded as double blind.

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