SUMMARY

Objective:

To perform a systematic review to answer the following research question: Is at-home bleaching in adults with more concentrated carbamide peroxide (CP) gels as effective and safe as bleaching performed with 10% carbamide peroxide gels?

Methods and Materials:

A comprehensive search was carried out in the MEDLINE via PubMed, Scopus, Web of Science, LILACS, BBO, Cochrane Library and SIGLE, without restrictions. IADR abstracts (1990 to 2016) and unpublished and ongoing trial registries, dissertations and theses (ProQuest Dissertations and Periodicos Capes Theses Databases) were also searched. The risk of bias of the included studies was analyzed using the Cochrane Risk of Bias tool from the Cochrane Collaboration. We meta-analyzed the data using the random effects model to compare 10% CP and more concentrated CP gels in terms of color change (ΔSGU or ΔE) and risk and intensity of tooth sensitivity (TS). The quality of the evidence was rated using the GRADE approach.

Results:

After the database screening, 182 articles remained, and this number was reduced to 17 after examination of the abstracts and/or full texts. Four articles were follow-ups of earlier studies, and thus we collected 13 studies. Ten studies were at unclear risk of bias, while three were at low risk of bias. Lower risk and intensity of TS was observed for 10% CP. The odds ratio for the risk of TS was 0.41 (95% CI 0.20 to 0.84, p=0.01), and the difference in means for TS intensity was 0.44 (95% CI 0.67 to −0.20, p=0.0003). No significant difference was observed in terms of color change in ΔSGU (difference in means 0.29; 95% CI 0.25 to 0.83, p=0.29) and for ΔE (difference in means −0.16; 95% CI 0.38 to 0.06, p=0.16). Except from the ΔSGU, for which the evidence was graded as low quality, the other outcomes were considered at moderate quality.

Conclusions:

At-home bleaching with 10% CP showed similar bleaching efficacy with lower risk and intensity of TS in comparison with more concentrated carbamide peroxide gels.

INTRODUCTION

At-home bleaching can be regarded as a popular cosmetic technique for treating dental discoloration since it provides rapid results, employs reduced chair time, and has lower risk of side effects compared to in-office bleaching.1-3 

The effectiveness of at-home whitening with 10% carbamide peroxide (CP) has been well reported in the literature.4-7  However, manufacturers have introduced different concentrations of CP (5% to 22%) for at-home bleaching8,9  and recommended their use for shorter periods of time.

Due to the continuing release of bleaching gels with different concentrations and protocols, choosing the best product for clinical recommendation is a very challenging task since clinicians should choose a product with similar or superior clinical effectiveness while maintaining patients' safety.

For selection of a bleaching agent, two aspects should be taken into consideration: the whitening efficacy and the risk of side effects. In regard to the former, some clinical studies have shown faster color change for bleaching gels with higher concentrations,10-12  while other studies did not detect significant differences in groups treated with 10% or more concentrated CP agents.4,13  In the same trend, the risk and intensity of tooth sensitivity (TS), which is the most common side effect of bleaching protocols, are shown to be similar4,10,13-15  or higher5,16-18  for more concentrated CP agents.

Therefore, attempts to reach a consensus to make the choice easier are of clinical interest. Consequently, the aim of this systematic review of the literature was to answer the following PICO question: Is 10% CP gel more effective in terms of color change and safer in terms of TS than bleaching gels with higher concentrations of CP for at-home bleaching in adults?

METHODS AND MATERIALS

Protocol and Registration

This study protocol was registered at PROSPERO (CRD42016029360), and we followed the recommendations of the PRISMA statement for the report of a systematic review.19 

Information Sources and Search Strategy

The controlled vocabulary (mesh terms) and free key word in the search strategy are in Table 1 and defined based on the following PICOS question reported in the end of the introduction section:

  1. Population (P): adult patients submitted to dental bleaching

  2. Intervention (I): at-home bleaching with 10% CP

  3. Comparison (C): at-home bleaching with more concentrated CP agents

  4. Outcome (O): risk and intensity of TS during dental bleaching and color change in shade guide units and in ΔE

  5. Study design (S): randomized clinical trials

The outcomes were not used in the search strategy to maximize the sensitivity of the search. To identify trials to be included for this review, we searched the electronic databases MEDLINE via PubMed, Scopus, Web of Science, Latin American and Caribbean Health Sciences Literature database (LILACS), Brazilian Library in Dentistry (BBO), and Cochrane Library. An expert librarian guided the whole search strategy. We hand searched the reference lists of all primary studies for additional relevant publications and the related articles link of each primary study in the PubMed database without restrictions to publication date or languages.

Other sources were also used to identify more articles. We searched the abstracts from the annual conference of the International Association for Dental Research (IADR) and the Brazilian regional division (1990–2016). We explored the gray literature using the database System for Information on Grey literature in Europe (SIGLE). Dissertations and theses were searched for using the ProQuest Dissertations and Theses Full Text database and the Periodicos Capes Theses database.

To locate unpublished and ongoing trials related to the review question, we searched the following clinical trials registries: Current Controlled Trials (http://www.controlled-trials.com), International Clinical trials registry platform (http://apps.who.int/trialsearch), ClinicalTrials.gov (http://www.clinicaltrials.gov), Rebec (http://www.rebec.gov.br), and EU Clinical Trials Register (http://www.clinicaltrialsregister.eu).

Eligibility Criteria

We included parallel and split-mouth randomized clinical trials (RCTs) that compared the risk and intensity of TS and color change after at-home bleaching with different concentrations of CP in adult patients of any age-group. The efficacy of the bleaching treatment was compared using the ΔSGU (shade guide units) and/or ΔE values.

RCT studies were excluded if studies compared 10% CP with 1) hydrogen peroxide, 2) in-office bleaching, 3) different placebos, 4) whitening toothpastes, 5) over-the-counter products, and 6) higher CP concentrations but did not measure any of the outcomes under investigation in this systematic review.

Study Selection and Data Collection Process

Initially, the articles were selected by title and abstracts according to the previously described search strategy. Articles that appeared in more than one database were considered only once. Full-text articles were also obtained when the title and abstract had insufficient information to make a clear decision. Subsequently, three reviewers (JLG, LMW, and TFB) classified those that met the inclusion criteria. To handle such a large number of studies, we used a study ID for each eligible study, combining first author and then year of publication. Data were extracted using customized extraction forms and the following data recorded for each included study:

  • Details of the study, including year of publication and author(s)

  • Details of study methods, including study design and setting

  • Details of participants, including age and gender

  • Details of bleaching protocol

  • Details of concentration of the bleaching gels

  • Details of TS perception using different types of scales

  • Details of color evaluation using shade guides and/or spectrophotometers

If there were multiple reports of the same study (ie, reports with different follow-ups), data from all reports were extracted directly into a single data collection form to avoid overlapping data. When data were not reported in the studies, we attempted to contact authors by e-mail at least twice to request the missing information.

When data from multiple bleaching sessions were provided, we made an average of the figures for each bleaching protocol. Concerning color change, we employed the data that represented the immediate result (up to three months postbleaching). When more than one concentrated CP agent was included in the study, their values were combined to make a single entry.

Risk of Bias in Individual Studies

Quality assessments of the selected trials were evaluated by three independent reviewers (JLG, LMW, and TFB) using the Cochrane Collaboration tool for assessing risk of bias in randomized trials.20  The assessment criteria contain six items: sequence generation, allocation concealment, blinding of the outcome assessors, incomplete outcome data, selective outcome reporting, and other possible sources of bias. During data selection and quality assessment, any disagreements between the reviewers were solved through discussion and, if needed, by consulting a fourth reviewer (AR).

For each aspect of the quality assessment, the risk of bias was scored following recommendations as described in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (http://handbook.cochrane.org). The judgment for each entry involved recording “yes,” indicating low risk of bias; “no,” indicating high risk of bias; and “unclear,” indicating either lack of information or uncertainty over the potential for bias.

For the outcomes risk, intensity of TS, and color change in shade guide units, studies were at “low” risk of bias if there was adequate sequence generation, allocation concealment, and blinding (key domains). For the objective evaluation of color in ΔE*, examiner blinding was not considered a key domain, as the foreknowledge of the treatment would not affect the results produced by the instrument tool.

To summarize the risk of bias within a study for each outcome, we followed the directions of the Cochrane Collaboration. An outcome of a study is at low risk of bias when all key domains for that outcome are at low risk of bias. The study was considered at unclear risk when one or more key domain was also unclear, and, finally, the study was at high risk of bias when at least one key domain was at high risk.

Summary Measures and Synthesis of the Results

Data from studies at low or unclear risk of bias were meta-analyzed using Revman 5 (Review Manager version 5, Cochrane Collaboration, Copenhagen, Denmark). Data from eligible studies were either dichotomous (absolute risk of TS) or continuous (intensity of TS, ΔSGU, and ΔE).

The outcomes were summarized by calculating the standardized mean difference for the continuous data and the odds ratio along with the 95% confidence interval (CI) for the dichotomous data. The random effects models were employed. Heterogeneity was assessed using the Cochran Q-test and I2 statistics. No subgroup analysis was performed. Sensitivity analyses were conducted to investigate the reasons for high heterogeneity whenever detected.

Assessment of the Quality of Evidence Using GRADE

We graded the quality of the evidence for each outcome across studies (body of evidence) using the Grading of Recommendations: Assessment, Development, and Evaluation (GRADE) (http://www.gradeworkinggroup.org) to determine the overall strength of evidence for each meta-analysis.21  The GRADE approach is used to contextualize or justify intervention recommendations with four levels of evidence quality, ranging from high to very low.

The GRADE approach begins with the study design (RCTs or observational studies) and then addresses five reasons (risk of bias, imprecision, inconsistency, indirectness of evidence, and publication bias) to possibly rate down the quality of the evidence (one or two levels) and three to possibly rate up the quality (large effect, management of confounding factors, and dose-response gradient).21  Each one of these topics was assessed as “no limitation,” “serious limitations,” and “very serious limitations” to allow categorization of the quality of the evidence for each outcome into high, moderate, low, and very low. “High quality” suggests that we are very confident that the true effect lies close to the estimate of the effect. On the other extreme, “very low quality” suggests that we have very little confidence in the effect estimate and that the estimate reported can be substantially different from what it was measured.

The GRADEpro Guideline Development Tool available online at http://www.gradepro.org) was used to create a summary of finding tables as suggested in the Cochrane Handbook for Systematic Reviews of Interventions.22 

RESULTS

Study Selection

After the database screening and removal of duplicates, 1418 studies were identified (Figure 1). After title screening, 182 studies remained, and this number was reduced to 22 after careful examination of the abstracts. After reading the articles, only 17 studies were included in the qualitative analysis.

Characteristics of the Included Articles

The characteristics of the 17 articles selected are listed in Table 2. Four articles were follow-ups of earlier studies, three from Meireles23-25  and one from Matis,12  totaling 13 studies from a total of 17 articles. The parallel study design was predominantly used in these studies.4,5,10,11,15-17,26,27  Four out of the 13 studies used the split-mouth design.13,14,18,28 

Three studies used a visual analog scale for pain evaluation,10,17,18  and six studies used a numeric rating scale.4,5,13,15,27,28  Three studies evaluated only the risk of TS,14,16,26  and one study did not evaluate this outcome.11 

For color evaluation, 10 studies used a shade guide.4,5,10,11,13,15,17,18,26,28  Eight used an objective instrument (spectrophotometer or colorimeter) for color assessment.4,11,13,15,17,18,27,28  Photographs or digital images were used in four studies.13,16,27,28  One study did not evaluate the color change.14 

The number of patients per group included in these studies ranged from 10 to 30. The average age of all participants included in the clinical trials was approximately 32.4 years.4,13-17  Seven studies did not report this information.5,10,11,18,26-28  In one study, most of the participants were male;17  in six articles, females predominated.4,5,13-16  Six studies did not report this information.10,11,18,26-28 

Bleaching Protocol and Features

Bleaching trays with reservoir were used in most of the studies.4,11,13,14,16,17,26-28  Three studies used custom-bleaching trays without reservoirs,5,15,18  and one study did not report this information.10 

Regarding the bleaching protocol (Table 2), CP with different concentrations, such as 12%,26  15%,10,13,15,16,18,28  16%,4,14,18  17%,11,17  20%,5,16,28  and 28%,27  were used for at-home bleaching.

The daily usage time of at-home bleaching gels varied from 20 minutes to overnight and the duration of bleaching in days varied from seven days to six months, but most of the studies performed bleaching for 14 days.10,13-16,26  (Table 2).

Assessment of the Risk of Bias

The risk of bias of the included studies is presented in Figure 2. Few full-text studies reported the method of randomization, allocation concealment, and whether the examiner was blinded during color assessment in shade guide units.

In summary, from the 13 studies, ten10,11,14-18,26-28  were considered at unclear risk of bias in the key domains of the Cochrane risk of bias tool, and three studies4,5,13  were classified at low risk of bias.

Meta-Analyses

All meta-analyses were performed on studies at low and unclear risk of bias and from which the information about the outcome could be extracted. For instance, we could not extract the data from the study of Leonard and others14  for any of the outcomes. The study of Turkun and others27  compared very different protocols between the two study groups, being four to six hours daily for 10% carbamide peroxide and only 20 minutes per day for 20% carbamide peroxide . Thus, from 13 studies, only 11 have data to be used at least in one of the outcomes of this study. This explains the variation in the number of studies in the forest plots of the different meta-analysies.

Risk of TS

This analysis was based on nine studies.4,5,10,15-18,26,28  The odds ratio was 0.41 (95% CI 0.20 to 0.84; p=0.01), which means that two people from the PC 10% will experience the event for every five who will not (Figure 3). Data were not heterogeneous (χ2 test, p=0.09; I2=41%; Figure 3), which means that all studies included in the analysis share a common effect size.

Intensity of TS

This analysis was based on six studies.4,5,10,15,17,28  The standardized difference in means was −0.44 (95% CI −0.67 to −0.20; p=0.0003). This provides evidence that there is a moderate difference,29  with lower intensity of pain for CP 10% than CP with higher concentrations (Figure 4). Data were not heterogeneous (χ2 test, p=0.34; I2=12%; Figure 4).

Color Change in ΔSGU

This analysis was based on seven studies.4,5,10,11,15,18,26  The standardized difference in means was 0.29, with a confidence interval varying from −0.25 to 0.83 (p=0.29). This showed that there was no difference in the color change measured in shade guide units (Figure 5). Data were heterogeneous (χ2 test, p<0.00001; I2=85%; Figure 5), which means that all studies included in the analysis did not share a common effect size. Through a sensitivity analysis, we did not identify the reason for this high heterogeneity.

Color Change in ΔE*

This analysis was based on five studies.4,13,15,16,18  The standardized difference in means was −0.16, with a confidence interval varying from −0.38 to 0.06 (p=0.16). These results show that there was no significant difference in the color change measured with a spectrophotometer (Figure 6). Data were not heterogeneous (χ2 test, p=0.56; I2=0%; Figure 5).

Assessment of the Quality of Evidence

In the summary of findings in Table 3, we can observe that except for the color change in ΔSGU, graded as low in the quality of evidence, the other outcomes were assessed as moderate quality using GRADE. The reasons for downgrading the evidence for ΔSGU were that most RCTs are at “unclear” risk of bias, presence of inconsistency with nonexplained statistical heterogeneity, and imprecision with a high 95% confidence interval, which does not exclude important harm or benefit (Table 3). For the other outcomes, the evidence was downgraded only for the unclear risk of bias of most RCTs.

DISCUSSION

In the present systematic review, we observed that at-home bleaching with 10% CP produced similar color change and lower risk and intensity of TS than at-home bleaching performed with more concentrated CP concentrations.

From a theoretical point of view, a faster or higher degree of color change was expected to occur with more concentrated CP gels. Chemical theories state that in simplest chemical reactions, an increase in the concentration of reactants may increase the reaction rate. Indeed, a closer look of several primary studies indicated that more concentrated CP products yielded a higher degree of whitening in the first days or week of bleaching,4,10,11  but this difference was not maintained at the end of the treatment.

For instance, Matis and others13  showed that a 15% CP gel achieved a higher degree of whitening than did the 10% CP gel after two weeks of use. However, by extending the treatment time to six weeks, the differences in color change or brightness were no longer statistically different. Similarly, Leonard and others14  concluded that higher CP concentrations achieved faster bleaching, but the results were equivalent, as longer application times were used for the lower CP concentrations.

When bleaching starts, the organic component of dentin has not been oxidized yet; therefore, a higher number of free radicals, available in highly concentrated CP products, have sufficient substrate for oxidization, leading to a higher degree of whitening at the beginning of bleaching. As time passes, the nonoxidized substrate reduces significantly, and the excess of active hydrogen peroxide in more concentrated CP products no longer has much substrate for action; while there are more available in dentin of those bleached with 10% CP. The lower concentration of active hydrogen peroxide in 10% CP gels is compensated for by the repetitive daily at-home bleaching protocol in a nonlinear trend. For instance, when 10% CP was applied in participants for eight hours daily, this group achieved faster bleaching than the group that used the product one hour daily; however, in just two more days, the color change of the one-hour group became similar to that of the eight-hour group.30 

Analogously, this also help us understand why a higher risk and intensity of TS was observed for higher-concentrated CP products. The surplus of hydrogen peroxide from highly concentrated products without substrate to oxidize reaches the organic component of the pulp tissue, where it may induce the formation of reactive or reparative dentin.31,32  Peroxides diffuse very quickly into dentin, reaching the pulp chamber, but the rate of penetration depends on the concentration and composition of the bleaching agent, the thickness of the hard tissue,33-36  and the application protocol.30  The higher the concentration of the bleaching agent, the greater the aggression to the pulp cells.31,32,37 

The damage caused by the hydrogen peroxide leads to the expression of inflammatory mediators, such as substance-P38  and prostaglandins, which have a recognized role in triggering nociceptive impulses for the perception of pain,39  helping us explain why higher-concentrated hydrogen peroxide could be responsible for the higher absolute risk and intensity of TS.

Most of the studies in dental bleaching use shade guides for color evaluation.4,5,10,11,13,17,18,26,28  Although these shade guides were designed primarily for shade matching with composite resins, their use is supported in the literature for evaluating bleaching efficacy.34,40-42  Compared with the spectrophotometer, the shade guides show better visual correlation and have the potential to allow for more accurate and consistent monitoring and reliable color of teeth.43 

It is worth mentioning that the conclusions herein collected are of moderate quality of evidence, and this means that we are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is different. The great limitation observed in this systematic review was the high number of studies at unclear risk of bias. Future studies with well-designed protocols, when added to the results collected so far in future systematic reviews of the same topic, may eventually lead the conclusions to high quality of evidence.

CONCLUSIONS

The 10% CP product demonstrated a significantly lower risk and intensity of TS when compared to higher CP concentrations without jeopardizing color change. In any case, these results should be interpreted with caution since most of the studies included in the meta-analysis were at unclear risk of bias.

Acknowledgment

This study was partially supported by the National Council for Scientific and Technological Development (CNPq) under grants 305588/2014-1 from Brazil.

Regulatory Statement

This study was conducted in accordance with all the provisions of the local human subjects oversight committee guidelines and policies of the State University of Ponta Grassa, Brazil.

Conflict of Interest

The authors of this article certify that they have no proprietary, financial, or other personal interest of any nature or kind in any product, service, and/or company that is presented in this article.

REFERENCES

1
Hasson
H,
Ismail
AI,
&
Neiva
G
(
2006
)
Home-based chemically-induced whitening of teeth in adults
Cochrane Database of Systematic Reviews
Oct 18(4) CD006202.
2
Zekonis
R,
Matis
BA,
Cochran
MA,
Al Shetri
SE,
Eckert
GJ,
&
Carlson
TJ
(
2003
)
Clinical evaluation of in-office and at-home bleaching treatments
Operative Dentistry
28
(
2
)
114
-
121
.
3
Rezende
M,
Loguercio
AD,
Kossatz
S,
&
Reis
A
(
2016
)
Predictive factors on the efficacy and risk/intensity of tooth sensitivity of dental bleaching: A multi regression and logistic analysis
Journal of Dentistry
45
1
-
6
.
4
Meireles
SS,
Heckmann
SS,
Leida
FL,
dos Santos Ida
S,
Della Bona
A,
&
Demarco
FF
(
2008
)
Efficacy and safety of 10% and 16% carbamide peroxide tooth-whitening gels: A randomized clinical trial
Operative Dentistry
33
(
6
)
606
-
612
.
5
Basting
RT,
Amaral
FLB,
França
FMG,
&
Flório
FM
(
2012
)
Clinical comparative study of the effectiveness of and tooth sensitivity to 10% and 20% carbamide peroxide home-use and 35% and 38% hydrogen peroxide in-office bleaching materials containing desensitizing agents
Operative Dentistry
37
(
5
)
464
-
473
.
6
Jadad
E,
Montoya
J,
Arana
G,
Gordillo
LA,
Palo
RM,
&
Loguercio
AD
(
2011
)
Spectrophotometric evaluation of color alterations with a new dental bleaching product in patients wearing orthodontic appliances
American Journal of Orthodontics and Dentofacial Orthopedics
140
(
1
)
e43
-
e47
.
7
Grobler
SR,
Hayward
R,
Wiese
S,
Moola
MH,
&
van
WKTJ
(
2010
)
Spectrophotometric assessment of the effectiveness of Opalescence PF 10%: A 14-month clinical study
Journal of Dentistry
38
(
2
)
113
-
117
.
8
Li
Y,
Lee
SS,
Cartwright
S,
Wilson
AC,
DeVizio
W,
Petrone
M,
Volpe
AR,
&
Zhang
YP
(
2004
)
Comparative tooth whitening efficacy of 18% carbamide peroxide liquid whitening gel using three different regimens
Journal of Clinical Dentistry
15
(
1
)
11
-
16
.
9
Matis
BA
(
2003
)
Tray whitening: What the evidence shows
Compendium of Continuing Education in Dentistry
24(4A) 354-362.
10
Kihn
PW,
Barnes
DM,
Romberg
E,
&
Petterson
K
(
2000
)
A clinical evaluation of 10 percent vs. 15 percent: Carbamide peroxide tooth-whitening agents
Journal of the American Dental Association
131
(
10
)
1478
-
1484
.
11
Braun
A,
Jepsen
S,
&
Krause
F
(
2007
)
Spectrophotometric and visual evaluation of vital tooth bleaching employing different carbamide peroxide concentrations
Dental Materials
23
(
2
)
165
-
169
.
12
Matis
BA,
Wang
Y,
Eckert
GJ,
Cochran
MA,
&
Jiang
T
(
2006
)
Extended bleaching of tetracycline-stained teeth: A 5-year study
Operative Dentistry
31
(
6
)
643
-
651
.
13
Matis
BA,
Mousa
HN,
Cochran
MA,
&
Eckert
GJ
(
2000
)
Clinical evaluation of bleaching agents of different concentrations
Quintessence International
31
(
5
)
303
-
310
.
14
Leonard
RH,
Garland
GE,
Eagle
JC,
&
Caplan
DJ
(
2002
)
Safety issues when using a 16% carbamide peroxide whitening solution
Journal of Esthetic and Restorative Dentistry
14
(
6
)
358
-
367
.
15
Alonso de la Pena
V,
&
Lopez Raton
M
(
2014
)
Randomized clinical trial on the efficacy and safety of four professional at-home tooth whitening gels
Operative Dentistry
39
(
2
)
136
-
143
.
16
Gerlach
RW,
Gibb
RD,
&
Sagel
PA
(
2000
)
A randomized clinical trial comparing a novel 5.3% hydrogen peroxide whitening strip to 10%, 15%, and 20% carbamide peroxide tray-based bleaching systems
Compendium of Continuing Education in Dentistry
(29) S22-S28.
17
Krause
F,
Jepsen
S,
&
Braun
A
(
2008
)
Subjective intensities of pain and contentment with treatment outcomes during tray bleaching of vital teeth employing different carbamide peroxide concentrations
Quintessence International
39
(
3
)
203
-
209
.
18
Bernardon
JK,
Vieira Martins
M,
Branco Rauber
G,
Monteiro Junior
S,
&
Baratieri
LN
(
2016
)
Clinical evaluation of different desensitizing agents in home-bleaching gels
Journal of Prosthetic Dentistry
115
(
6
)
692
-
696
.
19
Moher
D,
Liberati
A,
Tetzlaff
J,
&
Altman
DG
(
2009
)
Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement
British Medical Journal
339
b2535
.
20
Higgins
JP,
Altman
DG,
Gotzsche
PC,
Juni
P,
Moher
D,
Oxman
AD,
Savovic
J,
Schulz
KF,
Weeks
L,
Sterne
JA,
Cochrane Bias Methods Group, & Cochrane Statistical Methods Group
(
2011
)
The Cochrane Collaboration's tool for assessing risk of bias in randomised trials
British Medical Journal
343
d5928
.
21
Guyatt
GH,
Oxman
AD,
Schunemann
HJ,
Tugwell
P,
&
Knottnerus
A
(
2011
)
GRADE guidelines: A new series of articles in the Journal of Clinical Epidemiology
Journal of Clinical Epidemiology
64
(
4
)
380
-
382
.
22
Schünemann
HJ,
Oxman
AD,
Higgins
JPT,
Vist
GE,
Glasziou
P,
&
Guyatt
GH
(
2011
)
Chapter 11: Presenting results and “Summary of findings” tables
.
In
:
Higgins
JPT,
Green
S,
(
eds
)
Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0
The Cochrane Collaboration, Baltimore MD 335-338.
23
Meireles
SS,
Da Silva Dos Santos
I,
Delia Bona
A,
&
Demarco
FF
(
2009
)
A double-blind randomized controlled clinical trial of 10 percent versus 16 percent carbamide peroxide tooth-bleaching agents Journal of the American Dental Association 140(9) 1109-1117
.
24
Meireles
SS,
Heckmann
SS,
Santos
IS,
Della Bona
A,
&
Demarco
FF
(
2008
)
A double blind randomized clinical trial of at-home tooth bleaching using two carbamide peroxide concentrations: 6-month follow-up
Journal of Dentistry
36
(
11
)
878
-
884
.
25
Meireles
SS,
Santos
IS,
Bona
AD,
&
Demarco
FF
(
2010
)
A double-blind randomized clinical trial of two carbamide peroxide tooth bleaching agents: 2-year follow-up
Journal of Dentistry
38
(
12
)
956
-
963
.
26
Callan
RS,
Browning
WD,
Downey
MC,
&
Brackett
MG
(
2008
)
Comparison of two low sensitivity whiteners
American Journal of Dentistry
21
(
1
)
17
-
20
.
27
Türkün
M,
Celik
EU,
Alada
A,
&
Gökay
N
(
2010
)
One-year clinical evaluation of the efficacy of a new daytime at-home bleaching technique
Journal of Esthetic and Restorative Dentistry
22
(
2
)
139
-
146
.
28
Matis
BA,
Wang
YN,
Jiang
T,
&
Eckert
GJ
(
2002
)
Extended at-home bleaching of tetracycline-stained teeth with different concentrations of carbamide peroxide
Quintessence International
33
(
9
)
645
-
655
.
29
Cohen
J
(
1988
)
Statistical Power Analysis for the Behavioral Sciences
Erlbaum
,
Hillsdale, NJ
.
30
Cardoso
PC,
Reis
A,
Loguercio
A,
Vieira
LC,
&
Baratieri
LN
(
2010
)
Clinical effectiveness and tooth sensitivity associated with different bleaching times for a 10 percent carbamide peroxide gel
Journal of the American Dental Association
141
(
10
)
1213
-
1220
.
31
Soares
DG,
Basso
FG,
Hebling
J,
&
de Souza Costa
CA
(
2014
)
Concentrations of and application protocols for hydrogen peroxide bleaching gels: Effects on pulp cell viability and whitening efficacy
Journal of Dentistry
42
(
2
)
185
-
198
.
32
Soares
DG,
Basso
FG,
Pontes
ECV,
Garcia
LdFR,
Hebling
J,
&
de Souza Costa
CA
(
2014
)
Effective tooth-bleaching protocols capable of reducing H2O2 diffusion through enamel and dentine
Journal of Dentistry
42
351
-
358
.
33
de Oliveira Duque
CC,
Soares
DG,
Basso
FG,
Hebling
J,
&
de Souza Costa
CA
(
2017
)
Influence of enamel/dentin thickness on the toxic and esthetic effects of experimental in-office bleaching protocols
Clinical Oral Investigations
21
(
8
)
2509
-
2520
.
34
Bonafe
E,
Bacovis
CL,
Iensen
S,
Loguercio
AD,
Reis
A,
&
Kossatz
S
(
2013
)
Tooth sensitivity and efficacy of in-office bleaching in restored teeth
Journal of Dentistry
41
(
4
)
363
-
369
.
35
Marson
FC,
Goncalves
RS,
Silva
CO,
Cintra
LT,
Pascotto
RC,
Santos
PH,
&
Briso
AL
(
2015
)
Penetration of hydrogen peroxide and degradation rate of different bleaching products
Operative Dentistry
40
(
1
)
72
-
79
.
36
Roderjan
DA,
Stanislawczuk
R,
Hebling
J,
de Souza Costa
CA,
Soares
DG,
Reis
A,
&
Loguercio
AD
(
2014
)
Histopathological features of dental pulp tissue from bleached mandibular incisors
Journal of Materials Science and Engineering
12
(
6
)
178
-
185
.
37
Markowitz
K
(
2010
)
Pretty painful: Why does tooth bleaching hurt?
Medical Hypotheses
74
(
5
)
835
-
840
.
38
Caviedes-Bucheli
J,
Ariza-Garcia
G,
Restrepo-Mendez
S,
Rios-Osorio
N,
Lombana
N,
&
Munoz
HR
(
2008
)
The effect of tooth bleaching on substance P expression in human dental pulp
Journal of Endodontics
34
(
12
)
1462
-
1465
.
39
Huynh
MP,
&
Yagiela
JA
(
2003
)
Current concepts in acute pain management
Journal of the California Dental Association
31
(
5
)
419
-
427
.
40
Rezende
M,
Loguercio
AD,
Reis
A,
&
Kossatz
S
(
2013
)
Clinical effects of exposure to coffee during at-home vital bleaching
Operative Dentistry
38
(
6
)
E229
-
E236
.
41
de Geus
JL,
Bersezio
C,
Urrutia
J,
Yamada
T,
Fernandez
E,
Loguercio
AD,
Reis
A,
&
Kossatz
S
(
2015
)
Effectiveness of and tooth sensitivity with at-home bleaching in smokers: A multicenter clinical trial
Journal of the American Dental Association
146
(
4
)
233
-
240
.
42
Bernardon
JK,
Sartori
N,
Ballarin
A,
Perdigao
J,
Lopes
GC,
&
Baratieri
LN
(
2010
)
Clinical performance of vital bleaching techniques
Operative Dentistry
35
(
1
)
3
-
10
.
43
Paravina
RD,
Johnston
WM,
&
Powers
JM
(
2007
)
New shade guide for evaluation of tooth whitening—Colorimetric study
Journal of Esthetic and Restorative Dentistry
19
(
5
)
276
-
283
.