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Year : 2020  |  Volume : 31  |  Issue : 5  |  Page : 774-781
Post-operative pain after using sodium hypochlorite and chlorhexidine as irrigation solutions in endodontics: Systematic review and meta-analysis of randomised clinical trials

1 Dental School of Presidente Prudente, University of Western Sao Paulo, Presidente Prudente, SP; Graduate Program in Dentistry, University of Western Sao Paulo, Presidente Prudente, SP, Brazil
2 Graduate Program in Dentistry, University of Western Sao Paulo, Presidente Prudente, SP, Brazil
3 Dental School of Presidente Prudente, University of Western Sao Paulo, Presidente Prudente, SP, Brazil

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Date of Submission01-Apr-2019
Date of Decision13-Dec-2019
Date of Acceptance06-May-2020
Date of Web Publication08-Jan-2021


Context: Is it possible that the irrigating solutions can have the potential to cause post-operative pain? Unfortunately, the current literature does not provide clear guidance. Aim: The purpose of this systematic review and meta-analysis was to comprehensively review two different irrigation solutions (sodium hypochlorite and chlorhexidine) regarding the post-operative pain after endodontic treatment. Settings and Design: This study was prepared according to the Cochrane criteria for creating a systematic review and meta-analysis and confirms the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Material and Methods: This search was conducted in the PubMed/MEDLINE, SCOPUS and Cochrane Library databases until February 2018 to answer the In [(Population) what is the effect of (Intervention) on (Outcome), compared with (Comparison) Intervention] (PICO) question: could sodium hypochlorite cause more post-operative pain than chlorhexidine in teeth subjected to endodontic treatment? The primary outcome was overall post-operative pain after 24 h. Results: After applying the inclusion and exclusion criteria, three randomized clinical trials fulfilled the eligibility criteria, and two were subjected to the meta-analysis. There was no difference in post-operative pain between the tested irrigating solutions. Conclusions: There are few studies published in the current literature; therefore, additional randomized clinical studies are required to on this topic to help clinicians make the best decision concerning treatment.

Keywords: Endodontics, irrigating solution, post-operative pain, randomized clinical trial, systematic review

How to cite this article:
Martins CM, da Silva Machado NE, Giopatto BV, de Souza Batista VE, Marsicano JA, Mori GG. Post-operative pain after using sodium hypochlorite and chlorhexidine as irrigation solutions in endodontics: Systematic review and meta-analysis of randomised clinical trials. Indian J Dent Res 2020;31:774-81

How to cite this URL:
Martins CM, da Silva Machado NE, Giopatto BV, de Souza Batista VE, Marsicano JA, Mori GG. Post-operative pain after using sodium hypochlorite and chlorhexidine as irrigation solutions in endodontics: Systematic review and meta-analysis of randomised clinical trials. Indian J Dent Res [serial online] 2020 [cited 2021 Jan 18];31:774-81. Available from:

   Introduction Top

Currently, it is understood that the greatest difficulty in achieving successful endodontic treatment is to overcome the anatomy,[1] in order to clean and shape the root canal well.[2] Otherwise, an unfavourable outcome, such as post-operative pain, can occur.[3] Sathorn et al., in a 2008 systematic review, observed a prevalence rate ranging from 3% to 58% for pain after root canal treatment.[3] Most of the etiologic factors of postoperative pain were related to insufficient disinfection, poor removal of remaining tissue and the extrusion of infected debris into periapical tissue.[4],[5],[6]

Chemomechanical preparation is considered the most essential procedure to minimize microorganisms and pathologic debris and to remove the remaining tissue.[7] The literature indicates that instrumentation techniques are not completely effective for deep cleaning of the root canal system because of their peculiar anatomy.[8] Thus, it is necessary to use irrigation solutions because flushing can remove tissue remnants and bacteria in the root canal walls that are not touched by mechanical instrumentations.[9],[10],[11]

For decades, sodium hypochlorite (NaOCl) has been the most widely used irrigation solution for cleansing and disinfection of the root canal.[12],[13] The main characteristics of this substance are its antimicrobial activity, properties as an excellent organic solvent, lubricating activity and rapid action.[8],[12],[14],[15] However, NaOCl may be cytotoxic to the peri-radicular tissues, particularly at high concentrations.[16],[17] Additionally, NaOCl accidents commonly occur,[18] in which the substance extrudes beyond the apex, especially when using a conventional open-ended 30-G needle.[19] Kleier et al., in their retrospective study, showed that 42% of diplomates of the American Board of Endodontics reported having at least one NaOCl accident during their career.[20]

Chlorhexidine 2% (CHX) is available in liquid or gel form and can be used instead of NaOCl. CHX has antimicrobial action like NaOCl,[10] high substantivity, low toxicity and good lubricating activity.[21],[22] Some investigators have suggested CHX as a good choice of irrigation solution, especially in cases of persistent Enterococcus faecalis[23] and as a final irrigation solution.[24] Despite its advantages, CHX activity is reduced in the presence of organic substances because it is not an organic solvent.[23],[24] In addition, its activity is pH-dependent.[23],[24] In the current literature, allergic reactions to CHX have been described.[25],[26] Furthermore, CHX can triggers the release of by-products such as parachloroaniline and reactive oxide species, which are carcinogenic substances in humans.[27]

Considering that NaOCl and CHX are the irrigating solutions with the greatest clinical applicability, neither is considered ideal, and the question that clinicians who read the published articles has is as follows: what is the most appropriate irrigating solution for the treatment of teeth with the potential for post-operative pain? Unfortunately, the currently literature does not provide clear guidance.

Thus, the purpose of this systematic review and meta-analysis was to comprehensively review two different irrigation solutions (NaOCl and CHX) regarding post-operative pain after endodontic treatment. The null hypothesis was that there would be no difference in post-operative pain between the tested irrigation solutions.

   Materials and Methods Top

Registry protocol

This article was designed according to the Cochrane criteria[28] for elaborating a systematic review and meta-analysis. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement.[29] The study was registered at the International Prospective Register of Systematic Reviews (PROSPERO - Register n° 83771).

Eligibility criteria

The inclusion criteria were: (A) randomized controlled trials (RCT), (B) studies that evaluated post-operative pain in teeth with endodontic treatment, (C) studies that used sodium hypochlorite compared to chlorhexidine as an irrigation solution and (D) studies published in English language with available abstracts. Exclusion criteria included any articles that did not compare sodium hypochlorite with chlorhexidine and studies that evaluated irrigation methods but did not evaluate irrigation solutions.

A specific clinical question was structured according to the PICO approach: could sodium hypochlorite cause more post-operative pain than chlorhexidine in teeth subjected to endodontic treatment? In this process, (P) represents teeth submitted to endodontic treatment, and (I) represents chlorhexidine in comparison with (C) sodium hypochlorite regarding to (O) post-operative pain.

The overall post-operative pain after 24 h was the primary outcome to be extracted and analysed through meta-analysis.

Information sources

An electronic search of the PubMed/MEDLINE, SCOPUS and Cochrane Library databases was conducted up to February 2018. A manual search was conducted to identify gray literature and registered trials not yet published until February 2018 from the following journals: Journal of Dental Research, Journal of Endodontics, International Endodontic Journal, PLOS One, Journal of Oral Science, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology.


Two independent researchers (NESM and BGV) performed the electronic search of the selected databases. The keywords used were: (A) irrigating solution, (B) endodontics, (C) randomized clinical trial, and (D) post-operative pain. We performed keyword crossing as follows: #1 (irrigation solution and endodontics); #2 (irrigation solution and randomized clinical trial); #3 (irrigation solution and post-operative pain); #4 (irrigation solution and endodontics and randomized clinical trial); #5 (irrigation solution and endodontics and post-operative pain); #6 (irrigating solution and endodontics and randomized clinical trial and post-operative pain). Others keyword crossing were eliminated due to unspecific results with the purpose of our work. No filter was used in the databases.

Study selection

Two researchers (NESM and BGV) independently selected the studies according to their titles and abstracts and categorized them as included or excluded. Any disagreements were settled through discussion and consensus with another researcher (GGM). Then, the articles selected for inclusion were read by both investigators, and a manual search was performed of the reference lists.

Data collection process and data items

Subsequently, the full text of the obtained articles was analysed. The analysis of these selected articles was used to answer the PICO questions. One researcher (NESM) collected relevant information from the articles, including authors, year, study type, gender, average age, number of patients, tooth sample size, details of treatment (pulp condition, number of sessions, instrumentation technique, irrigating solution, irrigation protocol, irrigation final, and pain control), methods of pain analysis, follow-up and pain outcome. Then, a second researcher (BGV) checked all collected information. Another researcher (CMM) settled any disagreement between the investigators through discussion until a consensus was reached.

Risk of bias

The risk of bias assessment in the included studies was evaluated using the Cochrane Collaboration's tool for assessing risk of bias in randomized trials.[28] The assessment criteria are a domain-based evaluations in which critical assessments are made separately for different domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting and other bias.[28] For each domain, the risk of bias was graded as high, low, or unclear based on the criteria described in the Cochrane handbook for systematic reviews of interventions 5.1.0.[28] Two researchers (CMM and GGM) independently performed the risk of bias analysis.

Summary measures

The meta-analysis was based on the inverse variance (IV) method. Overall post-operative pain was the continuous outcome measure that was evaluated for mean difference (MD) and the corresponding 95% confidence intervals (CI). When statistically significant (P < 0.10) heterogeneity was detected, a random-effects model was used to assess the significance of treatment effects. When no statistically significant heterogeneity was found, the analysis was performed using a fixed-effects model.[30],[31] The MD values were considered significant when P < 0.05. The software program Reviewer Manager 5 (Cochrane Group) was used for the meta-analysis and to generate the funnel plot.

Bias risk among the studies

An asymmetric funnel plot may indicate publication bias or other biases related to sample size, although the asymmetry may also show a true relationship between trial size and effect size.[32] Heterogeneity was assessed using the Q method (x2) and the value of I2.[33] The outcomes were dichotomized into good and poor results. I2 values above 75 (range 0–100) were considered to indicate significant heterogeneity.[33]

Additional analysis

The kappa statistic was calculated to define the inter-reader agreement in the study selection process. According to Landis and Koch (1977), the level of inter-reader agreement is almost perfect if the value of Kappa (K) is 0.81–1.00, substantial if K is 0.61–0.80, moderate if K is 0.41–0.60, fair if K is 0.21–0.40 and poor if K is < 0.20.[34]

   Results Top

Study selection

A total of 785 articles were retrieved [Figure 1], of which only seven fulfilled the eligibility criteria (inter–reader agreement, Kappa = 0.71 for PubMed/Medline, Kappa = 1 for Cochrane Library and Kappa = 1 for Scopus). All the studies selected were randomised clinical trials that compared the post-operative pain after using sodium hypochlorite and chlorhexidine as irrigation solutions.[35],[36],[37]
Figure 1: Flow diagram of the articles selected

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Initially, four articles were selected and were subsequently excluded. Tachieri et al., in 2009,[38] and Gondim et al., in 2010,[39] performed a study, but they did not compare sodium hypochlorite with chlorhexidine. In its turn, Tannure et al., in 2011,[40] compared the efficiency of removing the smear layer using distinct irrigation solution. Ramamoorthi et al., in 2015,[41] evaluated post-operative pain using various irrigating techniques; however, they did not compare irrigating solutions.

Study characteristics

The selected articles were published in three journals: one[35] was published in the Indian Journal of Dental Research, another[36] in the Journal Canadian Dental Association and the other the Brazilian Dental Journal.[37] The number of cases ranged from 62 to 126.[35],[37] All articles aimed to analyse whether there is a difference in post-operative pain when using 5.25% sodium hypochlorite vs 2% chlorhexidine as irrigation solution in endodontics.[35],[36],[37]

Risk of bias within studies

The aspects evaluated for risk of bias can be found in [Table 1]. The articles of Bashetty and Hegde (2010) and da Silva et al. (2015) presented low risk of bias for most of key domains;[35],[37] and the article of Almeida et al. (2012) presented a similar number of low and high key domains.[36]
Table 1: Risk of bias among the studies

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Individual studies

A total of 254 patients, regardless of gender, with an average age of 37.1 years had 254 teeth treated endodontically. From these teeth, 126 teeth were irrigated using sodium hypochlorite and the remaining teeth were irrigated using chlorhexidine. All studies used 5.25% sodium hypochlorite and 2% chlorhexidine.[35],[36],[37] Bashetty and Hegde, in 2010, did not clarify the irrigation protocol used.[35] Almeida et al., in 2012, and da Silva et al., in 2015, used 2 mL and 3 mL, respectively, of the appropriate solution for each group each time instruments were switched, and both used passive ultrasonic irrigation (PUI) as a final irrigation.[36],[37] Almeida et al. removed smear layer with 10 mL of 17% ethylene diamine tetraacetic acid (EDTA) applied with an ultrasonic cavitation unit for 3 min, followed by a final washout with 5 mL of 5.25% NaOCl for the sodium hypochlorite group or 10 mL of normal saline for the chlorhexidine group.[36] Silva et al. also removed smear layer but only applying 3 mL of 17% EDTA for 3 min followed by irrigation with 3 mL of 5.25% NaOCl for the sodium hypochlorite group or 3 mL of normal saline for the chlorhexidine group.[36]

Vital pulp was diagnosed in 26 teeth and 228 teeth were diagnosed with pulp necrosis with the presence or absence of peri-apical lesion. Two studies performed endodontic treatment only on teeth with pulp necrosis.[36],[37]

The endodontic treatment was completed in a single visit in two studies,[36],[37] but Bashetty and Hegde, in 2010, that performed two-visit endodontic treatment, although they did not use any dressing between appointments.[35]

Each clinical trial used one instrumentation technique. Bashetty and Hegde, in 2010, used manual file in a crown-down technique: The canal orifices were enlarged using orifice shapers; initial glide path was obtained by using #10 K-file of 0.02 taper; working lengths were determined with an apex locator and confirmed radiographically; memory instrument were determined using an apical ISO size of 30 using the two cited different root canal irrigants with 30-gauge Max-i-Probe syringe that had been placed down the canal and 3 mm short from apex.[35]

Almeida et al., in 2012, modified the ProTaper universal technique: initial exploration was performed with a size 10 or size 15 K-file, followed by S1 and SX rotary files; coronal flaring was completed with size 4, 3 and 2 gates–glidden drills keeping a constant 5-mm distance from the radiographically determined apical limit, and in curved canals, going as far as the beginning of the curve; the preparation length was kept 1 mm short of the apical foramen, as defined by an apex locator; cavity refinement with a minimum size 25, 30 or 35 flexofile, depending on the anatomy of the canal; apical patency was maintained with a size 10 file.[36]

Da Silva et al., in 2015, used the Reciproc system according to the manufacturer's instructions: an initial exploration of the root canal was performed with size 10, 15 and 20 K-files and only cases where a 30 K-file did not go passively to the working length were selected; a R40 Reciproc instrument was advanced in the root canal; the working length was confirmed by an electronic apex locator; the irrigation solutions were kept in and dispensed using a 30-G Max-i-Probe needle up to 3 mm short of the working length.[37]

After completion of the endodontic treatment, only da Silva et al., in 2015, prescribed a single dose of 400 mg of ibuprofen to their patients.[37] Bashetty and Hegde, in 2010, asked the patients to take notes if they needed medication intake in order to exclude these patients.[35] Almeida et al., in 2012, did not prescribe analgesics and did not describe what they made if analgesics were used.[36]

The follow-up was completed mostly using 4-point scale from 6 h to 7 days after endodontic treatment. The main objective was to analyse the post-operative pain. As a conclusion, one study reported more pain using sodium hypochlorite,[35] only 6 h after the treatment, and the remaining studies reported no difference between the experimental groups.[36],[37]

The details regarding each study are present in [Table 2], and the main goal and their respective primary outcomes are synthesized in [Table 3].
Table 2: Summary of each study according to aim of the study and outcome

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Table 3: Articles included in the systematic review

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To answer the PICO question, the outcome was performed by two studies[35],[37] that reported the main of pain after 24 h of endodontic treatment using NaOCl and CLX irrigation solutions. There was no significant difference for pain (P = 0.28; MD: -0.10: 0.69; 95% CI: -0.29 to 0.08; x2 = 0.01, I2 = 0%) after using the different irrigating solution in the endodontic treatment [Figure 2]. The funnel plot [Figure 3] showed an evident symmetry among the differences in means for the studies evaluated, suggesting the absence of bias.
Figure 2: Forest plot of meta-analysis that evaluated the pain after 24 h from endodontic treatment using NaOCl and CHX irrigation solutions of two selected articles[35],[37]

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Figure 3: Funnel plot of meta-analysis with the studies evaluated

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   Discussion Top

Although the current literature suggests a high level of success in endodontic treatment,[42],[43],[44],[45] the presence of post-operative pain could pose an unfavourable outcome.[3] This systematic review addressed the influence of two irrigating solutions, NaOCl and CHX, on post-operative pain. It is important to emphasise that systematic review and meta-analysis of randomised clinical trials has a strong relationship with clinical reality. Based on these results, the null hypothesis of 'no difference in post-operative pain between the tested irrigation solutions' was confirmed.

After meta-analysis, there was not statistically significant difference regarding post-operative pain between 5.25% NaOCl and 2% CHX after 24 h. However, Bashetty and Hegde, in 2010,[35] observed that the 5.25% NaOCl group presented more pain than did 2% CHX only at the 6th hour post-operatively (P < 0.05). It is known that in the first hours after endodontic treatment there is a pain peak, which is uniquely related to the presence of inflammation.[46] After one day, pain begins to decrease significantly.[46] Nevertheless, Almeida et al., in 2012,[36] and da Silva et al., in 2015,[37] reported the first evaluation period time at 24 h after endodontic treatment and did not find differences between the groups in any experimental period.

In addition, the study of Bashetty and Hegde, in 2010,[35] was the only one to evaluate post-operative pain in teeth diagnosed with irreversible pulpitis. Endodontic treatment on vital pulp teeth seems to be associated with less post-operative pain. Asymptomatic necrotic pulp with a peri-apical lesion is the most likely pre-disposing clinical condition for the occurrence of post-operative pain.[47] On the other hand, NaOCl can be a toxic substance to the peri-apical tissues, especially because of its dissolution ability, and it can be related to pain and acute inflammation.[15],[18],[19],[20],[48] However, the relationship between pulp condition and post-operative pain using distinct irrigation solutions cannot be made through this systematic review.

Single-visit treatment was often performed,[36],[37] however, Bashetty and Hegde[35] performed endodontic treatment in two visits using no intracanal medications between visits. Single-visit root canal treatment is associated with less post-operative pain,[49] but the cited studies performed two visits to try to avoid confounding responses related to the obturation process, and they did not use intracanal medication for this reason.

Each study used one instrumentation technique and one type of instrument with a particular transverse section.[35],[36],[37] Martins et al. (2019) performed a systematic review to comprehensively review two different kinematics of instrumentation (reciprocating and rotary) and association to the post-operative pain after endodontic treatment. After meta-analysis, it was observed that rotary motion had a negative impact on post-operative pain after endodontic treatment. Furthermore, after 48 h, more patients presented severe pain under rotary motion.[50] Sun et al. (2018) also studied the incidence and intensity of post-operative pain after single-visit root canal treatment using manual, rotary and reciprocating instruments through systematic review, and they have observed that manual instrumentation leads to high levels of post-operative pain.[51] Both systematic reviews related post-operative pain to debris extrusion, which can lead to an inflammatory response, presenting pain as one of the five cardinal signs.[50],[51]

Nevertheless, the pattern of response was the same. The similarity among the techniques was the instrumentation in the crown-down direction, which was associated with the highest success rate and less post-operative pain due to minor debris extrusion.[52]

Regarding substances availability, NaOCl is commercially available in various concentrations.[53] There is a directly proportional relationship between concentration and toxicity, but overall, it has great cleaning and disinfection properties, antimicrobial activity and organic solvent properties.[8],[12],[14],[15],[18] All studies used 5.25% NaOCl,[35],[36],[37] but the concentration can range from 0.5% to 6%.[53]

CHX is available in solution or gel forms. Bashetty and Hegde (2010) used the solution,[35] and Almeida et al. (2012) and da Silva et al. (2015) used the gel form.[36],[37] As a consequence to gel form, the flushing ability is limited. To overcome this difficulty, a saline solution is used during the irrigating procedure.[36],[37] Studies have reported that both forms present similar properties: antimicrobial activity, especially against gram-positive bacteria, low toxicity and the absence of organic solvent.[10],[21],[22],[23]

Currently, there is a new endodontic concept: 'shaping for cleaning.'[53],[54] In other words, the chemo-mechanical preparation is an important step that is associated not only with the endodontic instruments but also with irrigating solutions. The instruments and instrumentation technique will provide the space for the irrigation solution to complete its function.[53],[54] The associations of techniques with forms of irrigation will allow greater success in this phase of endodontic treatment. Almeida et al., in 2012, and da Silva et al., in 2015, reported the use of passive ultrasonic irrigation as a final step in order to improve the quality, penetration and solution action.[36],[37] Therefore, the irrigation solution plays an important role. To the best of our knowledge, there is no ideal irrigation solution in the market. NaOCl and CHX are good solutions, but both have disadvantages. Therefore, the decision to use one or another solution should be made based on clinical case characteristics.[53],[54]

One important characteristic to be considered is the possibility of post-operative pain. Regardless of meta-analysis result, the main question of this study was not clearly answered due to the small number of studies; unpublished studies; the absence of studies that evaluated initial times of post-operative pain; and the absence of studies that correlate post-operative pain, pulp diagnosis and irrigating solutions. It is necessary to elucidate the importance of carrying out new randomised clinical studies in relation to this topic and to encourage new investigators to perform these studies.

Finally, this systematic review and meta-analysis indicate that there was no difference in terms of post-operative pain using NaOCl and CLX as irrigation solutions. There are few studies published in the current literature; therefore, additional randomised clinical studies are required on this topic to help clinicians make the best decision for the treatment of their patients.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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Correspondence Address:
Dr. Graziela G Mori
Rua José Bongiovani, 700 - Cidade Universitária - Presidente Prudente, SP
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijdr.IJDR_294_19

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