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AQ10 Recent Advances in Dental and BioAllied Sciences


1 The Impact of Chlorhexidine as an Endodontic Irrigant/Medicament 1
2 2
3 on Post‑Obturation Pain in Patients Following Endodontic Therapy: A 3
4
5
Preliminary Bayesian Meta‑Analysis 4
5
6 AQ9 Dexter R. Brave1, Akshayraj K. Langaliya2, Jasuma S. Rai3, Astha J. Buch4, Muktishree Mahendra5, Saloni Patel6 6
7 7
8 8
9
1
Department of Conservative Purpose: To assess the overall impact of chlorhexidine, when used as an endodontic 9

Abstract
Dentistry and Endodontics,
10
K M Shah Dental College
irrigant/medicament, on post‑obturation pain following endodontic treatment by 10
11 and Hospital, Sumandeep the application of Bayes methods of meta‑analysis. Settings and Design: This 11
12 Vidyapeeth, Vadodara, study aimed to combine recently documented evidence using rigorous and specific 12
13 Gujarat, India, 2Department search criteria. The available data were analyzed using Bayesian methods, which 13
14 of Conservative Dentistry have the advantage of accounting for uncertainties in estimates. This is in contrast 14
15 and Endodontics, AMC to commonly used frequentist meta‑analysis methods, which are not able to model 15
16 Dental College and Hospital, 16
Ahmedabad, Gujarat,
uncertainties as effectively, particularly when there is heterogeneity present.
17 Methodology: A preliminary search was conducted in the Pubmed, Cochrane, 17
18 India, 3Department of 18
Periodontology, K M Shah and Scielo databases using appropriate keywords. The search aimed to identify
19 19
Dental College and Hospital, human randomized clinical studies that evaluated post‑operative endodontic pain
20 Sumandeep Vidyapeeth, 20
and involved the use of chlorhexidine as an endodontic irrigant or medicament.
21 Vadodara, Gujarat, India, 21
22
Results: The preliminary Bayesian meta‑analysis produced a more accurate 22
4
Department of Conservative
23 Dentistry and Endodontics,
estimate compared to a frequentist random effect meta‑analysis model, with a 23
24 Faculty of Dental Sciences, narrower credible interval. The frequentist model demonstrated a detrimental 24
25 DDIT, Nadiad, Gujarat, India, impact of chlorhexidine on post‑obturation pain, while the Bayesian model 25
26
5
Department of Conservative indicated a somewhat favorable effect of chlorhexidine on post‑obturation pain. 26
27 Dentistry and Endodontics, Conclusion: Based on the scope of this investigation, it can be inferred that a 27
Bhabha College of Dental Bayesian random effects meta‑analysis model demonstrated a somewhat favorable
28 28
Sciences, Bhopal, Madhya
29 Pradesh, India, 6AMC
impact of chlorhexidine on post‑endodontic pain, which carries significant 29
30 AQ2 Dental College and Hospital, therapeutic significance. 30
31 AQ3 Austin, Texas 31
32 32
33 33
Submitted: 25‑Mar‑2024
34 AQ5 34
Revised: ???
35 Accepted: 02‑Apr‑2024 35
36 Published: *** Keywords: Chlorhexidine, endodontic irrigant, post‑obturation pain 36
37 37
38 38
Introduction The use of irrigation solutions and medicaments during
39 root canal preparation operations might potentially lead 39
40
41
42
T he primary objective of root canal treatment is
to attain a hermetic and impermeable seal of
the root canal system.[1] Post‑operative endodontic
40
41
42
Address for correspondence: Dr. Dexter Ralph Brave,
43 discomfort, which occurs after root canal treatment, is Department of Conservative Dentistry and Endodontics, 43
44 a prevalent yet uncomfortable ailment. The process of K M Shah Dental College and Hospital, Sumandeep 44
Vidyapeeth, Vadodara, Gujarat, India.
45 instrumentation relies on the clinician’s expertise and E‑mail: smilep91@gmail.com 45
46 other criteria, including the type of instrument and its 46
47 kinematics. Hence, post‑operative pain is regarded as This is an open access article distributed under the terms of the Creative Commons 47
Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak,
48 complex.[2] and build upon the work non‑commercially, as long as the author is credited and the new
48
49 creations are licensed under the identical terms. 49
50 Access this article online 50
Quick Response Code: For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
51 51
52 Website: https://journals.lww.com/jpbs 52
53 How to cite this article: Brave DR, Langaliya AK, Rai JS, Buch AJ, 53
Mahendra M, Patel S. The impact of chlorhexidine as an endodontic
54 irrigant/medicament on post‑obturation pain in patients following
54
55 DOI: 10.4103/jpbs.jpbs_284_24 endodontic therapy: A preliminary Bayesian meta‑analysis. J Pharm Bioall 55
56 Sci 2024;XX:XX-XX. 56

© 2024 Journal of Pharmacy and Bioallied Sciences | Published by Wolters Kluwer - Medknow 1
AQ1 Brave, et al.: ???

1 to irritation and chemomechanical damage to the tissues pain. Nevertheless, there is currently no comprehensive 1
2 around the root, which can result in post‑operative evaluation of the impact of chlorhexidine in diminishing 2
3 pain.[3] A comprehensive analysis revealed that the post‑operative endodontic discomfort that has been 3
4 occurrence of pain after root canal therapy varied recorded. 4
5 between 2.5% and 60%.[4] 5
6 This meta‑analysis aims to assess the cumulative effect 6
7 Chlorhexidine (CHX) can potentially decrease of chlorhexidine on post‑operative endodontic pain. It 7
8 post‑operative pain due to its effective antibacterial utilizes a Bayesian approach with a hierarchal structure 8
9 properties, long‑lasting effects, and minimal toxicity. to evaluate the impact of different moderator variables 9
10 Studies have demonstrated that using chlorhexidine that may influence the outcome of post‑operative 10
11 as a final irrigant in necrotic teeth can effectively endodontic pain. This analysis is necessary due to the 11
12 decrease post‑operative pain.[5] Nevertheless, a recent diverse nature of previous clinical studies on the subject. 12
13 comprehensive analysis examined the impact of 13
14
Inclusion criteria: This study includes human 14
chlorhexidine and sodium hypochlorite solution on clinical trials or studies that have performed primary
15 post‑operative pain and concluded no notable disparities 15
16 non‑surgical root canal therapy. The study must 16
between the two substances.[6] have employed chlorhexidine as one of the irrigants
17 17
18 Meta‑analysis is a robust method that enables researchers or medicaments. Additionally, the study must have 18
19 to combine and analyze data from multiple individual measured post‑operative endodontic pain using a 19
20 studies. It allows for the pooling of participants across standardized scale. 20
21 studies and facilitates the testing of hypotheses with high 21
22 statistical power, even when the individual studies have Methodology 22
23 limited power.[7] Additionally, meta‑analysis can assess An initial search was conducted based on the specified 23
24 the variability of effect sizes, which is also known as inclusion criteria in English across multiple databases 24
25 including Pubmed, Scielo, and Cochrane. The 25
effect size heterogeneity.
26 abstracts of the search results were examined for the 26
27 Meta‑analytic investigations employ either a fixed‑effect 27
pertinent discoveries. Articles meeting the specified
28 model, which assumes that all observed effect sizes in 28
criteria in their abstracts were chosen for full‑text
29 the sample originate from a single genuine underlying 29
retrieval and subsequently included in meta‑analyses.
30 effect, or a random‑effects model, which assumes that the 30
31 Following the extraction of pertinent data from the 31
true underlying effect may vary across studies.[8] Another individual full‑text articles provided, a preliminary
32 benefit of meta‑analyses is the ability to examine factors 32
33 Bayesian random‑effects meta‑analysis was conducted 33
that may have influenced variations between studies using the R programming language. This analysis
34 34
through moderator analyses.[9] For instance, let us was then compared to a frequentist random effects
35 35
consider a scenario where half of the research indicates meta‑analysis. Both studies were conducted using
36 36
37 a favorable impact, while the remaining half indicates an the R programming language. After doing an initial 37
38 unfavorable impact. Meta‑analyses can be employed to search, the following studies were selected for this 38
39 examine hypotheses regarding potential moderators that preliminary analysis: 39
40 elucidate this discrepancy. 40
41 The study conducted by Kurt et al. in 2018 41
Bayesian approaches can be employed as a means to do
42 meta‑analyses. Similar to traditional methods, Bayesian The study conducted by Almeida et al. in 2012 42
43 43
meta‑analyses gather information from previous studies, The study conducted by Selen et al. in 2022 provides
44 44
identify tiny effects, and analyze how different factors valuable insights.
45 45
46 affect the results of the studies.[10] 46
The publication by Shetty and Hegde in 2010
47 Nevertheless, the Bayesian technique offers numerous 47
48 supplementary advantages for researchers in practical Results 48
49 settings. Bayesian meta‑analyses allow researchers to 49
Random‑Effects Model by the Frequentist Approach AQ4
50 measure the strength of the evidence supporting both the 50
51
(k = 4; tau^2 estimator: REML) 51
alternative and null hypotheses using the Bayes factor.[11]
52 logLik deviance 52
53 AQ6 Rationale for the research 53
54 ‑6.3835 12.7670 54
A recent systematic study conducted a comparative
55 analysis of the effectiveness of sodium hypochlorite and tau^2 (estimated amount of total heterogeneity): 55
56 chlorhexidine in alleviating post‑operative endodontic 1.7989 (SE = 3.3690) 56

2 Journal of Pharmacy and Bioallied Sciences ¦ Volume XX ¦ Issue XX ¦ Month 2024


AQ1 Brave, et al.: ???

1 tau (square root of estimated tau^2 value): 1.3412 assessed the impact of chlorhexidine on post‑operative 1
2 endodontic pain after 24 hours. 2
I^2 (total heterogeneity/total variability): 43.61%
3 3
4 All the studies included in the analysis examined the 4
H^2 (total variability/sampling variability): 1.77
5 impact of chlorhexidine on post‑operative endodontic 5
6 Test for Heterogeneity: pain at different time intervals. However, for this 6
7 Q (df = 3) =5.3178, p‑val = 0.1499 preliminary analysis, the results from the 24‑hour 7
8 time point were selected from each study to ensure a 8
9 Model Results: consistent temporal effect analysis. 9
10 estimate se pval The odds ratio was used as the effect size for 10
11 11
‑5.6444 1.0156 <.0001 this investigation because of its widespread usage
12 12
in meta‑analysis. The frequentist random effects
13 13
meta‑analysis yielded a broad variation and an
14 14
15
estimated mean of ‑5.64, demonstrating a negative 15
16 effect of chlorhexidine on post‑operative endodontic 16
17 pain. The substantial disparity may be attributed to 17
18 the existence of numerous confounding factors in each 18
19 study (heterogeneity = 43.6%). These were excluded 19
20 from this initial analysis. The odds ratio, calculated using 20
21 the log odds ratio, was employed as the effect size in 21
22 this investigation. The log odds ratio quantifies the level 22
23 of correlation between the dependent and independent 23
24 variables in a distribution that follows a normal pattern. 24
25 25
The Bayesian random effects meta‑analysis yielded a
26 Study1 ‑ Kurt et al. (2018) 26
27 mean log odds ratio of 0.42, demonstrating a favorable 27
Study 2 ‑ Almeida et al. (2012) association between the utilization of chlorhexidine and
28 28
Study 3 ‑ Selen et al. (2022) post‑endodontic discomfort. There is a slight positive
29 29
Study 4 ‑ KB Shetty and Hegde (2010) correlation between the usage of chlorhexidine and
30 30
31 Bayes random effects meta‑analysis post‑endodontic discomfort. 31
32 However, doing additional tests to assess 32
marginal posterior summary:
33 multi‑collinearity among the variables and performing 33
34 tau mu 34
time series analysis to examine the impact at different
35 mode 0.0000000 ‑5.6354228 35
time intervals are necessary to enhance the reliability
36 36
median 0.3644859 ‑5.6356671 and predictability of the outcome analysis.
37 37
mean 0.4244321 ‑5.6358237
38 38
39
sd 0.3130008 0.8062803 Conclusion 39
40 95% lower 0.0000000 ‑7.2183400 In this investigation, chlorhexidine showed a slightly 40
41 95% upper 1.0222201 ‑4.0535073 favorable impact on post‑endodontic pain when employed 41
42 as an endodontic irrigant or medicament. Nevertheless, it 42
43 Discussion is advisable to do more analyses to allow for sensitivity 43
44 Bayesian meta‑analyses enable researchers to integrate analysis, moderator analysis, multi‑collinearity, and 44
45 their understanding of a phenomenon into the study by reparametrization, as well as Bayesian meta‑regression, if 45
46 utilizing a prior distribution.[12] Crucially, meta‑analytic applicable for a more accurate exploration of the impact 46
47 evidence may be regularly updated as new research of other factors on post‑obturation discomfort. 47
48 becomes available.[13] 48
49 Financial support and sponsorship 49
50 Acquiring evidence that supports the null hypothesis is Nil. 50
51 particularly significant given the replication crisis,[14] and 51
Conflicts of interest
52 Bayesian meta‑analyses allow for the same to evaluate 52
whether the overall data support the null or alternative There are no conflicts of interest.
53 53
54 hypothesis.[15] 54
55
References 55
The included studies exhibited a significant degree 1. Lee S‑H, Oh S, Al‑Ghamdi AS, Mandorah AO, Kum K‑Y,
56 56
of variation at the inter‑study level. All studies solely Chang SW. Sealing ability of AH plus and guttaflow bioseal.

Journal of Pharmacy and Bioallied Sciences ¦ Volume XX ¦ Issue XX ¦ Month 2024 3


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1 Bioinorg Chem Appl 2020;2020:8892561. 8. 1


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2 2. Zawrzykraj E, Krużyński W, Radwański M, AQ7
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E‑J. A primer on Bayesian model‑averaged meta‑analysis. Adv
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of randomised clinical trials. Indian J Dent Res 2020;31: meta‑analyses and preregistered multiple‑laboratory replication
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