Adults versus children

10 ‐ no studies with just children

Gingivitis alone versus gingivitis with perio

8

0.12

‐0.14 to 0.38

Increase in GI effect estimate for gingivitis and perio

0.30

Prophylaxis or not

9

0.05

‐0.22 to 0.32

Increase in GI effect estimate for prophylaxis

0.66

Baseline gingivitis < 1 versus > 1

9

0.02

‐0.25 to 0.30

Increase in GI effect estimate for higher baseline score

0.84

Adults versus children

13

‐0.17

‐0.42 to 0.09

Increase in GI effect estimate for adults

0.185

Gingivitis alone versus gingivitis with perio

9

0.15

‐0.14 to 0.44

Increase in GI effect estimate for gingivitis and perio

0.25

Prophylaxis or not

11

‐0.13

‐0.25 to ‐0.004

Increase in GI effect estimate for no prophylaxis

0.045

Baseline gingivitis

< 1 versus > 1

9

‐0.05

‐0.39 to 0.30

Decrease in GI effect estimate for higher baseline score

0.75

4 to 6 weeks

0.2

6 (552)

MD ‐0.27 (‐0.46 to ‐0.09)

0.003 favours CHX

0.41

0.1 and 0.12

5 (253)

MD ‐0.19 (‐0.27 to ‐0.10)

< 0.0001 favours CHX

6 months

0.2

1 (86)

MD ‐0.12 (‐0.20 to ‐0.04)

0.005

Too few studies in subgroup

0.1 and 0.12

10 (2352)

MD ‐0.22 (‐0.33 to ‐0.11)

< 0.00001 favours CHX

0.05

1 (150)

MD ‐0.04 (‐0.11 to 0.03)

0.28

4 to 6 weeks

0.2

4 (472)

SMD ‐0.71 (‐0.90 to ‐0.51)

< 0.00001 favours CHX

0.18

0.1 and 0.12

3 (127)

SMD ‐0.32 (‐0.85 to 0.21)

0.23

6 months

0.2

2 (155)

SMD ‐1.20 (‐2.48 to 0.08)

0.07

0.34

0.12

6 (977)

SMD ‐0.57 (‐0.79 to ‐0.36)

< 0.00001 favours CHX

4 to 6 weeks

0.2

8 (685)

SMD ‐1.75 (‐2.45 to ‐1.04)

< 0.00001 favours CHX

0.04

0.1 and 0.12

4 (215)

SMD ‐0.95 (‐1.23 to ‐0.66)

< 0.00001 favours CHX

6 months

0.2

2 (149)

SMD ‐1.26 (‐1.61 to ‐0.90)

< 0.00001 favours Chx

0.65

0.1 and 0.12

8 (1898)

SMD ‐1.38 (‐1.75 to ‐1.00)

< 0.00001 favours CHX

4 to 6 weeks

0.12

1 (52)

MD 0.01 (‐0.21 to 0.23)

0.93

7 to 12 weeks

0.2

2 (159)

SMD ‐0.03 (‐0.43 to 0.36)

0.86

0.05

0.12

4 (266)

SMD 0.52 (0.13 to 0.91)

0.10

6 months

0.2

2 (149)

SMD 0.41 (0.09 to 0.74)

0.01

0.005

0.12

2 (174)

SMD 1.17 (0.76 to 1.59)

< 0.00001 favours control

4 to 6 weeks

0.2

2 (116)

SMD 1.45 (1.04 to 1.87)

< 0.00001 favours control

0.05

0.1 and 0.12

6 (299)

SMD 0.96 (0.68 to 1.24)

< 0.00001 favours control

7 to 12 weeks

0.2

3 (181)

SMD 1.38 (1.05 to 1.71)

< 0.00001 favours control

0.10

0.12

7 (361)

SMD 1.2 (0.96 to 1.45)

< 0.00001 favours control

0.05

1 (39)

SMD 0.59 (‐0.05 to 1.24)

0.07

6 months

0.2

2 (149)

SMD 1.79 (1.41 to 2.17)

< 0.00001 favours control

0.08

0.12

2 (174)

SMD 1.33 (1.00 to 1.66)

< 0.00001 favours control

4 to 6 weeks

Twice per day

9 (785)

MD ‐0.22 (‐0.33 to ‐0.11)

< 0.0001

Too few studies in subgroup

Once per day

1 (20)

MD ‐0.13 (‐0.31 to 0.06)

0.18

6 months

Twice per day

11 (1614)

MD ‐0.17 (‐0.20 to ‐0.13)

< 0.0001

0.56

Once per day

2 (1002)

MD ‐0.34 (‐0.93 to 0.25)

0.26

4 to 6 weeks

Twice per day

8 (649)

SMD ‐0.56 (‐0.79 to ‐0.33)

< 0.0001

‐

6 months

Twice per day

8 (1132)

SMD ‐0.72 (‐1.02 to ‐0.42)

< 0.0001

‐

4 to 6 weeks

Twice per day

11 (930)

SMD ‐1.49 (‐1.97 to ‐1.02)

< 0.0001

Too few studies in subgroup

Once per day

1 (20)

SMD ‐0.92 (‐1.86 to 0.02)

0.05

6 months

Twice per day

10 (1223)

SMD ‐1.34 (‐1.66 to ‐1.03)

< 0.0001

Too few studies in subgroup

Once a day

1 (852)

SMD ‐2.10 (‐2.27 to ‐1.93)

< 0.0001

4 to 6 weeks

Twice per day

1 (50)

MD 0.03 (‐0.11 to 0.17)

0.70

‐

7 to 12 weeks

Twice per day

5 (373)

SMD 0.33 (‐0.11 to 0.77)

0.14

‐

6 months

Twice per day

4 (323)

SMD 0.80 (0.33 to 1.26)

0.0007

‐

4 to 6 weeks

3 times per day

1 (33)

SMD 1.55 (0.76 to 2.34)

< 0.0001

Too few studies in subgroup

Twice per day

5 (310)

SMD 1.18 (0.93 to 1.44)

< 0.0001

Once per day

1(20)

SMD 0.39 (‐0.5 to 1.28)

0.39

7 to 12 weeks

3 times per day

1 (33)

SMD 0.77 (0.06 to 1.48)

0.03

Too few studies in subgroup

Twice per day

9 (496)

SMD 1.26 (1.04 to 1.49)

< 0.0001

6 months

Twice per day

4 (323)

SMD 1.54 (1.22 to 1.86)

< 0.0001

‐

Results for studies with no rinse control arms

7 to 12 weeks

< 0.1

2 (196)

MD ‐0.07 (‐0.16 to 0.02)

0.13 favours CHX

P = 0.19, I² = 40%

7 to 12 weeks

< 0.1

2 (196)

SMD ‐0.77 (‐1.07 to ‐0.47)

< 0.00001 favours CHX

P = 0.61, I² = 0%

Results for studies with placebo/control rinse arms

7 to 12 weeks

0.2 and 0.12

4 (144)

MD ‐0.47 (‐0.76 to ‐0.18)

0.001 favours CHX

P < 0.0001, I² = 86%

> 6 months

0.1 and 0.12

2 (1124)

MD ‐0.50 (‐1.11 to 0.11)

0.11 favours CHX

P < 0.0001, I² = 99%

7 to 12 weeks

0.12 and < 0.1

5 (182)

SMD ‐1.29 (‐1.85 to ‐0.72)

< 0.00001 favours CHX

P = 0.02, I² = 64%

Long term

0.12

3 (99)

MD ‐0.12 (‐0.2 to ‐0.04)

0.003 favours CHX

P = 0.33, I² = 11%

7 to 12 weeks

0.2, 0.12 and < 0.1

10 (423)

SMD ‐1.74 (‐2.51 to ‐0.98)

< 0.00001 favours CHX

P < 0.00001, I² = 91%

> 6 months

0.1

1 (852)

MD ‐1.55 (‐1.79 to ‐1.31)

< 0.00001 favours CHX

N/A

Long term

0.12

4 (132)

SMD ‐1.10 (‐1.18 to ‐0.40)

< 0.002 favours CHX

P = 0.02, I² = 71%

Anauate‐Netto 2014

CHX 0.12% vs placebo

PBS

0.9 (0.6)

0.7 (0.4)

40

Did not report GI. Quote: "..no statistically significant differences were detected among groups"

Anderson 1997

CHX 0.12% vs placebo

GI

0.345

0.895

28

Reported mean GI by surface + SD. No overall SD. We calculated overall mean. Quote: "The means of the …gingival indices did not show any significant differences (P<0.05) 1 or 2 months after baseline. However there were significant differences (P<0.05) in the changes recorded at 30 and 60 days at all sites in…..the experimental group"

de la Rosa 1888b

CHX 0.12% vs placebo

PMGI severity (mean score of all sites graded)

0.1413

0.2902

92

Did not report GI or a SD. Quote: "..the effect of the chlorhexidine rinse on the occurrence and severity of gingivitis amounted to a 51% reduction of the disease compared to the placebo rinse…differences were statistically significant"

de la Rosa 1988a

CHX 0.12% vs placebo

PMGI severity (mean score of all sites graded)

0.2892

0.4526

99

Did not report GI or a SD. Quote: "..the gingivitis reductions were 34% and 36% for occurrence and severity respectively…differences were statistically significant"

Eaton 1997

CHX 0.12% vs placebo

mGI

0.42 (0.383)

0.55 (0.382)

98

Did not report GI. Quote: "..the pooled mean mGI score improved by 25% from 0.56 at baseline to 0.42 at 12 weeks in the ChD (CHX) group but showed no change (0.54 to 0.55) in the placebo group"

Ferretti 1987

CHX 0.12% vs placebo

PMGI

0.8

1.94

33

Did not report GI and SD depicted in graph but not reported. Quote: "Significant reductions in …gingivitis scores were seen on days 33 (P<0.0001) and 60… (P<0.001) for those patients using chlorhexidine rinse"

Segreto 1986

0.2% vs 0.12% vs placebo

GI

0.4112/0.3640

0.5039

454

Did not report a SD. Quote: "Gingivitis severity by the GI method was… significantly lower at 3 months for both chlorhexidine groups compared to the placebo group. Differences ranged from 28‐46% and averaged 37% for the 0.12% group. Differences ranged from 18‐40% for the 0.20% group and averaged 29%"

Weitz 1992

CHX 0.12% vs placebo

GI

1.69

1.86

36

Did not report a SD. Quote: "…the active (CHX) groups had significantly lower… gingivitis scores than the respective control groups. Overall, the active group had a 10.27% reduction in the gingival index…compared to insignificant changes in the control groups"

Fine 1985

CHX+OH vs OH

Not clear. Quote: "a gingival inflammation Index"

NR

NR

83

Outcomes reported in graphs which are difficult to decipher. Quote: "Whilst there was a general improvement in all… groups of patients, no one group was statistically significantly different from the other…"

Hoffmann 2001

CHX 0.1%, CHX 0.06%, CHX 0.06%+F vs control

GI

Median 0.15/0.29/0.34

Median 0.45

58

No SD. At 3 months "..only the 0.1% CHX was different from the control". At 6 months "…the 0.1% CHX showed significant differences…in the GI…when compared to the 0.06% CHX/F" (P = 0.043)

Overholser 1990

CHX 0.12% vs control

mGI

0.81 (SE 0.065)

1.166 (SE 0.063)

83

Did not report a SD. Quote: "PX (CHX) inhibited gingivitis development by 26.8% (P<0.001) at 3 months and by 30.5% (P<0.001) at 6 months, compared to the control"

Axelsson 1987

CHX 0.2% vs CHX 0.1% vs placebo

Mean % of gingival units with GI score 2 or 3

12%/11%

25%

64

Did not report a SD. Quote: "In all…study groups, the % of gingival units scored GI 2+3 was reduced between baseline..and end of trial"

Graziani 2015

CHX 0.2%+Alc vs CHX 0.2% no Alc vs CHX+ADS vs control rinse

FMBS /BOP

Not clear

13.47%

70

Partial reporting of outcome data. Quote: "Statistically significant decreases in mean full‐mouth scores of gingival inflammation were noted for all experimental study groups at day 35 compared to baseline. Between‐group changes in FMBS…were statistically significant only when CHX2 (mean difference of 43.4 ± 22.4, P = 0.05) and CHX 3 (mean difference of 46.1 ± 23.1, P = 0.05) were compared to the CTRL group" (note: CHX 2 = CHX no Alc, CHX 3 = CHX + ADS)

Sanz 1989

CHX 0.12% vs placebo

Mean % sites GI score 2 and 3

18.78%

31.31%

38

Did not report a SD. Quote: "Beginning at 4 weeks of rinsing, gingival bleeding was significantly lower in the CHX group compared to the placebo group by an average of 41.6% (P < 0.05). At 6 weeks that reduction was 40%, (P < 0.05)"

Corbet 1997

CHX 0.12% vs placebo

Mean % sites GI score 2 and 3

27%(anterior)

42%(posterior)

52%(anterior)

75%(posterior)

36

Did not report a SD. Quote: "The difference between the mean percentage of GB of the test and control groups at 3 months was highly significant (P < 0.001)"

Segreto 1986

CHX 0.2% vs CHX 0.12% vs placebo

Mean % sites GI score 2 and 3

Examiner A: 3.4%/2%

Examiner B: 7.2%/6.2%

Examiner A: 3.81%

Examiner B: 14.9%

454

Did not report a SD.

O.2% Quote: "Bleeding was 31% lower (range 11‐52%) compared to the placebo group" (P > 0.05)

0.12% Quote: "..gingival bleeding was significantly lower by an average of 53% for both examiners (range 48‐59%)" (P ≤ 0.05)

Banting 1989

CHX 0.12% vs placebo

Mean % sites GI score 2 and 3

2.41%

4.12%

383

Did not report a SD. Regarding outcomes at 6 months to 2 years: Quote: "Subjects in the treatment group…displayed between 42% and 51% fewer sites with moderate to severe gingivitis (GI scores of 2 or 3) compared with subjects in the control group" (P < 0.0001)

Charles 2004

CHX 0.12% vs control

Mean % sites GI score 2 and 3

11.01%

20.65%

1156 sites

% of bleeding sites in each group is presented. There is a unit of analysis error (number of sites rather than number of subjects). Quote: "There was a considerable reduction in percent bleeding sites in the chlorhexidine…groups at 6 months compared with both control and baseline"

Lucas 1999

CHX 0.12% vs placebo

Mean % sites GI score 2 and 3

1%

4.2%

20

Did not report a SD. Quote: "Although the percentage of bleeding surfaces in the chlorhexidine group was less than in the placebo group on days 90 (33%) and 180 (76%), the differences were not significant" (P = 0.07)

Sanz 1994

CHX 0.12% vs placebo

% sites GI score 2 and 3

Graph

Graph

130

% bleeding sites reported incompletely in text and also in a graph. Did not report a SD.

Quote: "At 6 months…the positive control group had significantly fewer bleeding sites than the control group (.. 23%...)"

Banting 1989

CHX 0.12% vs placebo

Mean % sites GI score 2 and 3

4.41%

8.88%

272

Did not report a SD. Regarding outcomes at 6 months to 2 years: Quote: "Subjects in the treatment group…displayed between 42% and 51% fewer sites with moderate to severe gingivitis (GI scores of 2 or 3) compared with subjects in the control group" (P < 0.0001)

Sanz 1989

CHX 0.12% vs placebo

PI

0.452

0.9907

38

Did not report a SD

Anderson 1997

CHX 0.12% vs placebo

PI

0.3175*

0.8425*

28

Mean GI by surface + SD reported. We calculated the overall mean. No overall SD

de la Rosa 1888b

CHX 0.12% vs placebo

TQH

NR

NR

92

Quote: "The reductions in dental plaque were not statistically significant.."

de la Rosa 1988a

CHX 0.12% vs placebo

TQH

NR

NR

99

Quote: "The reductions in dental plaque were not statistically significant.."

Segreto 1986

0.2% vs 0.12% vs placebo

TQH

1.14/1.01

1.58

451

Did not report a SD

Weitz 1992

CHX 0.12% vs placebo

PI

1.84

2.21

36

Did not report a SD

Banting 1989

CHX 0.12% vs placebo

TQH

Graph

Graph

383

Data presented in a graph. Did not report a SD. Quote: "Subjects in the treatment group had significantly lower mean plaque scores than those in the control group at six months, and at one and two years. The difference between the groups ranged from 35% to 46%"

Hoffmann 2001

CHX 0.1%/CHX 0.06%/CHX 0.06%+F vs control rinse

PI

Median 0.13/0.25/0.27

Median 0.72

58

Median only. Did not report a SD

Jayaprakash 2007

CHX 0.05%/ CHX 0.05%+F vs placebo

PI

0.0813/0.0459

0.1189

100

Did not report a SD

Lucas 1999

CHX 0.12% vs placebo

OHI‐S

0.33

0.59

20

Did not report a SD

Sanz 1994

CHX 0.12% vs placebo

PI

Graph

Graph

130

Data presented in a graph. Did not report a SD. Quote: "…reductions in Plaque Index...were statistically significant for the positive control group…compared with the reduction obtained with the control group.. These reductions were 41% (positive control)…after 3 months and 35%..after 6 months.."

Banting 1989

CHX 0.12% vs placebo

TQH

Graph

Graph

272

Data presented in a graph. Did not report a SD. Quote: "Subjects in the treatment group had significantly lower mean plaque scores than those in the control group at six months, and at one and two years. The difference between the groups ranged from 35% to 46%"

Anderson 1997

CHX 0.12% vs placebo

RI

0.1075

0.0475

29

Mean RI by surface + SD reported. We calculated overall mean. No overall SD

Anderson 1997

CHX 0.12% vs placebo

RI

0.0875

0.0525

28

Mean RI by surface + SD reported. We calculated overall mean. No overall SD

Charles 2004

CHX 0.12% vs control

VM

0.37 (SD NR)

0.11 (SD NR)

74

Did not report a SD

Sanz 1994

CHX 0.12% vs placebo

VM

Graph

Graph

130

Data presented in graph. Did not report a SD. Quote: "All groups developed calculus after the initial cleaning at baseline. This increase was only statistically significant for the positive control group compared with the control group at 6 months"

Banting 1989

CHX 0.12% vs placebo

VM

NR

NR

383

Results reported at 24 months only. See results at > 6 months below

Charles 2004

CHX 0.12% vs control

VM

0.45 (SD NR)

0.21 (SD NR)

73

Did not report a SD

Grossman 1986

CHX 0.12% vs placebo

Not specified

NR

NR

380

Quote: "Supragingival calculus was higher in the group using chlorhexidine but this increase in calculus did not diminish the therapeutic effects of chlorhexidine since subjects with significant increases in calculus also had significant decreases in gingivitis"

Sanz 1994

CHX 0.12% vs placebo

VM

Graph

Graph

130

Data presented in a graph. Did not report a SD. Quote: "All groups developed calculus after the initial cleaning at baseline. This increase was only statistically significant for the positive control group compared with the control group at 6 months"

Banting 1989

CHX 0.12% vs placebo

VM

NR

NR

272

At 24 months subjects in the treatment group had higher mean supragingival calculus scores, but at the same time more subjects were free of subgingival calculus

Axelsson 1987

CHX 0.2%/0.1% vs control

DI (Lobene)

0.1171 (0.297)

0

64

Not included in meta‐analysis as control mean is 0. We combined data from the 0.2% and 0.1% CHX groups

Bhat 2014

CHX 0.2% vs control

Reported number and proportion of participants with mild or moderate 'discolouration' in text

20 (91%)

0

44

Not clear whether discolouration relates to teeth or oral tissues or both

Flotra 1972 & 1971 (4‐month study that reports this outcome at 4 weeks)

CHX 0.2%/0.1%/0.1% (acetate) vs control

No index

Reported narratively

12% of tooth surfaces without fillings

62% of silicate fillings

NR

48 (at 4 weeks)

Quote: "..12% of the tooth surfaces without fillings became discolored within the first 4 weeks of the experiment…this happened more frequently on the interproximal surfaces than on the labial surfaces (ratio2:1). Sixty‐two per cent of the silicate fillings in these areas were discolored.."

Graziani 2015

CHX 0.2% vs control

SI

0.2228 (0.18)

0

70

Not included in meta‐analysis as control mean is 0. We combined data from the 3 CHX groups

Hase 1995

CHX 0.2% vs placebo

Subjective of participants regarding staining of teeth and/or tongue using VAS

38 (SE 7)

9 (SE 1)

39

Teeth and/or tongue staining reported together. Data estimated from a graph

López‐Jornet 2012

CHX 0.2% vs placebo

Registration of side effects including denture/dental staining (n and %)

2 (5.71%)

3 (8.57%)

70

Denture and dental staining reported together

Turkoglu 2009

CHX (conc not reported) vs placebo

No index

Reported narratively

14 (56%)

Assumed 0

50

Quote: "Of the 25 subjects who rinsed their mouth with CHX mouthrinse..14 showed discolouration of teeth and/or tongue"

Zimmer 2006

CHX 0.06%+F+OH vs OH

Staining of teeth and tongue registered at final examination (n)

4

0

78

Stain on teeth/tongue reported together. If more than 1 side effect was present, only the most relevant was listed i.e. side effects were reported with no double counting

Charles 2004

CHX 0.12% vs control

DI (Lobene)

1.61 (SD NR)

0.01 (SD NR)

74

Did not report a SD

Grossman 1989

CHX 0.12% vs placebo

Not specified Quote: "Photographs of facial surfaces of the 12 anterior teeth (maxillary and mandibular, cuspid to cuspid) were graded for stain intensity and coverage"

4.66 (SD NR)

2.59 (SD NR)

246

Did not report a SD

Sanz 1994

CHX 0.12% vs placebo

Not specified

NR

NR

130

Data presented in a graph at 6 months only See 6‐month results below

Zimmer 2006

CHX 0.06% +F+OH vs OH

Staining of teeth and tongue registered at final examination (n)

6

0

78

Stain on teeth/tongue reported together. If more than 1 side effect was present, only the most relevant was listed i.e. side effects were reported with no double counting

Charles 2004

CHX 0.12% vs control

DI (Lobene)

2.08 (SD NR)

0.01 (SD NR)

73

Did not report a SD

Grossman 1986

CHX 0.12% vs placebo

Not specified

NR

NR

380

Outcome data not reported. Quote: "Some extrinsic tooth staining was observed in the chlorhexidine group"

Grossman 1989

CHX 0.12% vs placebo

Not specified Quote: "Photographs of facial surfaces of the 12 anterior teeth (maxillary and mandibular, cuspid to cuspid) were graded for stain intensity and coverage"

5.15 (SD NR)

2.75 (SD NR)

246

Did not report a SD

Hoffmann 2001

CHX 0.1%/ 0.06%/0.06%+F vs control

DI (Lang and Räber)

1.13/1.02/1.06 (SD NR)

0.38 (SD NR)

58

Median only. Did not report a SD

Sanz 1994

CHX 0.12% vs placebo

Not specified Quote: "Photographs of facial surfaces of the 12 anterior teeth (maxillary and mandibular, cuspid to cuspid) were graded for stain intensity and coverage"

Graph

Graph

130

Data presented in graph Did not report a SD

Quote: "Statistically significant more overall staining, more intense staining and stain coverage per tooth were detected for the positive control group…compared with the control group"