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Year : 2023  |  Volume : 26  |  Issue : 2  |  Page : 134-142
Comparative evaluation of calcium hydroxide and other intracanal medicaments on postoperative pain in patients undergoing endodontic treatment: A systematic review and meta-analysis

Department of Conservative Dentistry and Endodontics, Y. M. T Dental College and Hospital, Kharghar, Navi Mumbai, Maharashtra, India

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Date of Submission11-Sep-2022
Date of Decision23-Nov-2022
Date of Acceptance28-Nov-2022
Date of Web Publication16-Mar-2023


Aim: The aim of this study was to evaluate the effect upon postoperative pain in teeth of patients suffering from apical periodontitis or necrotic pulp when treated with calcium hydroxide and compare it with other intracanal medicaments.
Materials and Methods: MEDLINE database, PubMed and Google Scholar databases were searched based on the filters and inclusion and exclusion criteria. The screening was done to finally acquire 9 articles from the mass of searched articles. The data extraction followed the screening process, and qualitative and quantitative data were recorded. The risk of bias was conducted with the Cochrane Collaboration tool, and meta-analysis was done using Review Manager version 5.3.
Results: A total of 9 studies over the past five decades met the inclusion criteria for full-text reading, and all 9 of them were included for further analysis. When we assessed for pain outcome, in comparison with CHX and Ca(OH), the cumulative mean difference was −4.57 (confidence interval: −16.25, 7.11). The heterogeneity was significant I2 = 95%, hence we applied the random effects model. The mean difference showed that the mean pain outcome was more in the control (Ca(OH)) group, as compared to the intervention group.
Conclusion: Calcium hydroxide is effective in reducing posttreatment pain when it is used alone, but its effectiveness can be increased when used in combination with other medicaments such as chlorhexidine.

Keywords: Chlorhexidine; debris; dental pulp; endodontics; heterogeneity; pain

How to cite this article:
Hegde VR, Jain A, Patekar SB. Comparative evaluation of calcium hydroxide and other intracanal medicaments on postoperative pain in patients undergoing endodontic treatment: A systematic review and meta-analysis. J Conserv Dent 2023;26:134-42

How to cite this URL:
Hegde VR, Jain A, Patekar SB. Comparative evaluation of calcium hydroxide and other intracanal medicaments on postoperative pain in patients undergoing endodontic treatment: A systematic review and meta-analysis. J Conserv Dent [serial online] 2023 [cited 2023 May 29];26:134-42. Available from:

   Introduction Top

Pain of endodontic origin has been a major concern to patients and clinicians for many years. It may occur as a result of several factors, including chemical, mechanical, or bacterial irritation to the periapical tissues.[1],[2] Even when the endodontist has followed all appropriate standards of care, postendodontic pain is common in dentistry. Pulp therapy and root canal treatment (RCT) cause more frequent and severe postoperative pain than other dental operational treatments, according to previously published research.[2] The factors involved can be categorized as: (1) predisposing or host-related factors, such as patient's age, gender, tooth type, host's immunity, psychological factors, and local tissue changes; (2) the iatrogenic factors, such as overinstrumentation and chemical or obturating material extrusion; and (3) the microbial factors.[2] The iatrogenic errors can be avoided by a careful root canal preparation technique. Common reason for the postoperative endodontic pain occurs when the infected debris of the necrosed tooth gets extruded into the periapical area.[3] Mechanical variables, such as poor root canal instrumentation, apical debris extrusion, loss of the interappointment seal during endodontic treatment, and loss of apical constriction, may all contribute to postendodontic pain. Thus, to kill and remove microorganisms, their by-products, and remnant tissue, as well as remove the smear layer and other debris from the canal system, some sort of irrigation and disinfection is required. Irrigants, canal rinses, and interappointment medicaments are three types of chemicals (therapeutic) RCTs; calcium hydroxide is included in the latter group. In order to destroy any germs that survive the chemico-mechanical preparation, antibacterial intracanal medicaments have been advised.[4] Various intracanal medicaments are used in dentistry with wide range of uses, such as reducing the amount of residual bacteria after root canal instrumentation, decreasing postoperative inflammation, and effectively managing pain.[5] Calcium hydroxide is the most frequently used antimicrobial intracanal medicament, and it is extensively compared to other medicaments in the literature. Farhad and Mohammadi (2005) described it as a white odorless powder with the chemical formula Ca(OH) 2 and a molecular weight of 74.08. It has a low solubility in water (about 1.2 g L) 1 at 25°C, which diminishes as the temperature rises (Siqueira and Lopes 1999). It has a bactericidal and bacteriostatic effect at first, as well as a high pH. It also has the potential to reduce inflammation and repair damage.[6] Double antibiotic paste is a combination of metronidazole and ciprofloxacin that is used as an intracanal antibiotic for necrotic tooth disinfection. It has been shown to be useful in lowering the number of bacteria in infected root canals. Antibiotic paste can be used to treat teeth with extensive periapical lesions when conventional medications fail to relieve the symptoms.[7] Gram-negative, Gram-positive, and anaerobic bacteria are all affected by triple antibiotic paste which contains ciprofloxacin, metronidazole, and minocycline, and this combination can be helpful against odontogenic germs.[7],[8],[9],[10] In medicine, topical anesthetic treatments have been investigated in the past to relieve postoperative pain. In dental analgesia, lidocaine hydrochloride (HCl) is a regularly used local anesthetic. Lidocaine HCl can also be used as a topical anesthetic on the injection site or wound surfaces. In teeth with irreversible pulpitis and symptomatic apical period pain, the calcium hydroxide mixed with lidocaine HCl group may be effective in lowering postoperative pain.[11],[12],[13] To deal with the symptoms of postoperative endodontic pain, nonsteroidal anti-inflammatory drugs, systemic antibiotics, and corticosteroids can be given, but these agents need to be placed locally at the site of pain origin which is the root canal system.[14] Chlorhexidine is a broad-spectrum antimicrobial agent and has been advocated as an effective intracanal medicament in endodontics. The advantages of chlorhexidine are its retentive character in root canal dentin and its relatively low toxicity. In addition, it is also effective against strains resistant to calcium hydroxide. Some studies have suggested that chlorhexidine could be used in combination with calcium hydroxide to improve the antimicrobial efficacy against calcium hydroxide-resistant microorganisms. Although this combination has been tested for the reduction of postoperative pain, there was no control and no attempt was made to quantify the degree of pain relief.[15] Recently, the focus of research has shifted toward finding natural alternatives to synthetic medications.[16],[17] A systematic review is therefore conducted to review how the calcium hydroxide medication improves postoperative pain in patients undergoing RCT.

   Materials and Methods Top

Protocol and registration

The protocol was designed and recorded as per the Preferred Reported Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol statement,[18] and the same protocol was registered at PROSPERO International prospective register of systematic reviews ('prospero) under the registration number CRD42022304181.

Focused question

The systematic review aimed to answer the following question: what is the effect upon postoperative pain in teeth of patients suffering from apical periodontitis or necrotic pulp when treated with calcium hydroxide and comparing it with other intracanal medicaments?

The Population, Intervention, Comparison, and Outcome format was used to define a focused clinical question.

  • Population/participants: Patients diagnosed with apical periodontitis or necrotic pulp
  • Intervention: Conventional Ca(OH) 2
  • Comparison: Other intracanal medicaments (chlorhexidine, Ledermix, double antibiotic paste, lidocaine HCl, propolis, Ca(OH) mixed with dexamethasone, and TAP)
  • Outcome: Postoperative pain by Visual Analog Scale (VAS)

Inclusion criteria

The following studies were included in the study:

  • Randomized controlled trial (RCT)
  • Prospective studies with before–after comparisons
  • Studies must include calcium hydroxide (control group), and other intracanal medicaments, and studies must assess patients treated for apical periodontitis/necrotic pulp
  • Pain was the outcome of interest assessed in the study (postoperative).

Exclusion criteria

Reviews, case reports, abstracts, editorials, letters, studies including animal experiments and historical reviews, and in vitro studies were not included in the review.

Information sources

Electronic databases: MEDLINE database via PubMed, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), PROSPERO register was searched for studies in English, reporting on post-operative pain following the use of intra-canal medicaments in patients. The last search was performed in October 2021.

Search strategy

Two reviewers independently performed the search. Combinations of controlled terms (MeSH), keywords, and Boolean operators were used whenever possible. A detailed description of the search strategy is detailed in [Table 1].
Table 1: Electronic databases and search strategies according to the Population, Intervention, Comparison, and Outcome question components

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Study selection

After duplicate records have been removed by manual screening, two investigators independently performed the study selection by initially screening the title and abstract according to the inclusion criteria. Inclusion of articles for the full-text analyses was performed only after a mutual agreement between the two. Where there were disagreements, it was resolved by means of a consensus discussion presided over by the third reviewer. In instances of multiple studies from the same cohort or topic, if the publications reported different outcomes, both studies were included; if the similar outcome was seen at different visits, all the studies were included with pain outcome used for subgroup quantitative analysis. Inter-reviewer agreement was measured through Cohen's kappa (k = 0.88).

Data extraction

Data extraction was performed independently by the two reviewers according to the aims of the present systematic review and was reciprocally blinded to each other's extraction. Disagreements between the review authors were discussed and resolved with a third review author. The data extracted comprise the characteristics of the eligible studies which were put into the piloted data extraction sheet.

Data items

The following primary information was extracted from the selected articles: name of author, year of publication, country, study design, age of participants, gender, sample size, method of randomization, type of tooth, intervention-CHX, antibiotic paste, propolis, dexamethasone, TAP, Ledermix, nitrofurantoin, control-Ca(OH), outcome-VAS pain score, and author conclusion

Risk of bias within studies and quality assessment

Risk of bias within studies was independently evaluated by two review authors. The Cochrane Risk-of-Bias Tool for RCTs was used and the studies were classified as low (if all domains were at low risk of bias), unclear (if there was an unclear risk of bias of at least one domain), or high risk of bias (if at least one domain was scored as being at a high risk of bias). The following domains were assessed: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessor, incomplete outcome data, selective outcome reporting, and other sources of bias. Discrepancies between the review authors were discussed until consensus was reached.[19]

Risk of bias within studies

Risk of bias within the studies was evaluated independently by two review researchers. The studies were classified as low risk of bias, unclear, and high-risk bias.

Data analysis

After following the search strategy and application of selection criteria, 9 articles were selected for qualitative assessment. The cumulative mean difference was calculated for comparing the effectiveness of intracanal medicaments (CHX) and calcium hydroxide. The heterogeneity amongst studies was assessed as per the values of I2 and Cochrane Q to identify the statistical model to base applied, hence fixed/random effects model (Mantel-Haenszel) was applied wherever indicated. Since there were five studies, publication bias was not assessed as more than 5 studies are required to detect funnel plot asymmetry.[20]

Risk of bias

The methodological quality of individual selected studies was done using the risk-of-bias assessment tool as elaborated in the Cochrane handbook of systematic reviews of intervention (version 5.1.0) published in 2011 by John wiley and sons ltd.[19] The results are presented in [Figure 2]b and [Figure 2]c as the risk-of-bias graph and summary, respectively, which were generated using the RevMan software (v5.3). There are six domains under which the methodology of individual studies is assessed and granted a level of risk. The quality assessment of 9 included studies was done with representation [Figure 2]b and [Figure 2]c. All the studies had a moderate level of methodology overall that could be followed and none had a high risk of level of quality.
Figure 2: (a) Forest plot for pain assessment CHX versus Ca(OH) (b) Risk of bias graph: Review authors judgements about each risk of bias item presented as percentages across all included studies. (c) Risk of bias summary: review authors judgements about each risk of bias item for each included study

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   Result Top

[Figure 1] (PRISMA flowchart) depicts the summarized study selection. A total of 9 studies over the past five decades met the inclusion criteria for full-text reading and all 9 were included in further analysis.
Figure 1: PRISMA flow diagram showing the studies exclusion and final inclusion with reasons

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Study characteristics

Nine articles were selected from screening of the abovementioned number of articles by two independent reviewers. Following which, careful examination and discussion was conducted depending on the selection criteria. Any discrepancies in opinion were resolved by the third reviewer. Ultimately, nine articles were finalized for qualitative synthesis. Studies fitting the inclusion criteria underwent validity assessment and data extraction, and other studies were excluded. The data provided in the selected studies should contain and were recorded in Excel sheets under the headings: author, year of study, journal, region, age, gender, sample size, method of randomization, tooth type, treatment and control group details with outcome details, and author conclusions.

The publication year of studies varied from 2013 to 2021. A cumulative total of 728 patients were included in the nine studies. The male and females were in varying sample sizes. The sample size ranged from 18 to 128 patients per group. The studies were conducted all over the globe; most studies took place in Asia,[6],[7],[17],[21],[22],[23] Egypt,[8] Europe,[2] and Turkey.[11] The method of randomization was mostly simple randomization by lottery or computer-generated number in all the studies included. The study design was RCTs. The age of the patients ranged from 20 to 45 years.

The treatment group included different medicaments such as CHX, in combination of CHX and Ca(OH), double antibiotic paste, propolis, dexamethasone, Ledermix, and nitrofurantoin, while the control group was consistent with Ca(OH) used as a medicament.

The primary outcome was pain which was measured by VAS in all the studies. The data were recorded as continuous data in mean and standard deviation format as pre- and postintervention. Quantitative analysis was performed for two selective studies of CHX as experimental group and Ca(OH) as control group.

The meta-analysis was conducted on 2 studies which have data outcome that could be used for analysis. The results as a Forest plot are depicted in figures. With the meta-analysis conducted for the selected studies, the heterogeneity was analyzed for each outcome. The comparison for pain was done with subgroup analysis.

When we assessed for pain outcome, in comparison with CHX and Ca(OH), the cumulative mean difference was − 4.57 (CI: −16.25, 7.11). The heterogeneity was significant I2 = 95%, hence we applied the random effects model. The mean difference showed that the mean pain outcome was more in the control (Ca(OH)) group, as compared to the intervention group [Figure 2]a.

Publication bias

Publication bias was not assessed for these outcomes. The studies were less than 5 in number to assess the same.

   Discussion Top

Pain is the most common reason to consult a physician. It is the main symptom in many medical and dental conditions and can significantly alter the person's quality of life and general functioning.[24] Endodontic posttreatment pain remains to be a significant problem facing the dental profession.[6] Endodontic pain may occur before, during, or after endodontic treatment.[24]

The main rationale of endodontic treatment is to retain teeth affected by pulpal or periradicular diseases. Root canal infection is the main etiologic factor of apical periodontitis[25] and endodontic failure.[26]

The most common cause of postoperative pain is the presence of microorganisms in the root canal system due to improper disinfection of the canals.[4]

The antimicrobial dressing should have factors that enable the greatest possible and most long-lasting effect against a spectrum of bacterial species and not cause irritation of periapical tissue. The use of calcium hydroxide in reducing intracanal bacteria has been suggested.[27] Calcium hydroxide alters bacterial cell walls and denatures a potent endotoxin,[28] a lipopolysaccharide, thereby rendering it less antigenic.[28],[29] It has been studied that calcium hydroxide has pain-preventive properties because of its antimicrobial or tissue-altering effects and it controls inflammatory process in-turn inducing repair.[27],[28]

In the current review, two electronic databases were accessed and searched, with filters such as free-text and controlled-vocabulary terms that represent sources for published and gray literature without any restriction to date, language, or publication status to achieve comprehensive search. Two reviewers independently performed the identification of the screened studies and data extraction. Risk of bias assessment was done for individual studies. The authors of the trials were contacted via e-mail if any case of missing data. Inclusion criteria reflected the population most likely to receive an intracanal medicament nonsurgical endodontic treatment of patients having mature teeth with nonvital pulp. The best study design to answer a therapeutic clinical question is a randomized clinical trial, which was the only design included in the present review.

A total of 16 articles were included in this systematic review, which included 728 participants with 780 teeth, of which 780 were analyzed. Studies having compared CH to no or various other Intracanal medicaments (ICMs) were included. However, very handful studies were included in most comparisons precluding the possibility of drawing valid, reliable conclusions. Most of the studies had a relatively small size (8 of 9 articles with <100 participants) [Table 2]. Despite the relatively homogenous clinical procedures across studies, there was existence of statistical heterogeneity which could influence the validity of the pooled estimates during the meta-analysis that we conducted for the selective two studies. Most studies showed a high risk of bias relative to most outcomes which further downgrades the certainty of estimates.
Table 2: Characteristics of individual studies

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According to the RoB with Cochrane Collaboration tool, only three articles[2],[8],[11] of the included 13 assessing postoperative pain showed a low risk of bias. Most of the included articles showed an overall moderate risk of bias on the outcome level mostly due to having a high risk of bias in the domain of “bias and blinding in measurement of the outcome” which is attributed to the lack of information about blinding of the outcome assessor to the intervention regarding participant-reported outcomes (e.g., pain).[19]

In four studies, Ledermix was compared with calcium hydroxide,[24],[9],[12],[30] and three studies concluded that Ledermix is better than calcium hydroxide in reducing posttreatment pain.

Out of these nine studies, seven studies have concluded that there is a better outcome from any medicament (intervention) and the calcium hydroxide groups. Only two studies quantitatively concluded that calcium hydroxide is not better in reducing pain than the other medicament group. This limited action of calcium hydroxide could be because of the buffering effect that dentin exerts over calcium hydroxide, reducing its anti-microbial action. In addition, few studies[31],[32] found that certain bacteria found in the root canal system were resistant to high pH of calcium hydroxide.

The better attributes of CHX and its enhancing effect to CH (calcium hydroxide) in controlling postoperative painful incidents compared to CH alone have been demonstrated in several studies.[6],[33],[34],[35] This has been due to factors of CHX's such as high diffusibility, substantivity, and better effectiveness against resistant microbiota (e.g., Enterococcus faecalis and Candida albicans); its addition to CH also had a positive effect on CH's antimicrobial activity and the medication wettability to dentin.[36],[37],[38],[39] Moreover, the effectiveness of chlorhexidine as intracanal medication in controlling the postoperative pain might be because of its ability to reduce or eliminate the endotoxins associated with the development of spontaneous pain.

Another study done by Menakaya et al.[40] showed that there is a significant postoperative pain reduction in teeth dressed with chlorhexidine alone or in combination with calcium hydroxide than those teeth dressed with calcium hydroxide or placebo.

Through this systematic review, we aimed to contribute whether there was a decrease in postoperative pain after endodontic treatment with calcium hydroxide or other newly available ICMs. We followed stringent inclusion and exclusion criteria by the two reviewers in assistance with the third reviewer for better validity. Although there was a variation in the publication year of studies, all studies were randomized trials conducted all over the globe. Hence, we got an outlook on the effect of these intracanal medicaments and their responses in all types on patients. Even with various antibiotic pastes available, clinicians still use CHX as over Ca(OH).

Meta-analysis was conducted on two studies, as the outcome of interest was not available in other studies. Furthermore, the heterogeneity was high in the two studies involved owing to the use of random effects model. We exaggerate that there should be more studies conducted in near future with outcomes that are uniform and can be analyzed with meta-analysis for different interventions.

The risk of bias was overall moderate to low in the included studies which indicated that investigators did follow appropriate methods or protocols for conducting RCT, however, attrition bias was common which needs to be considered with calculating sample size to avoid reducing the power of the study and improve its reliability of results.

There is a need for future studies to use other antibiotic pastes and newer intracanal medicaments to be used in patients, so that further systematic reviews and meta-analyses can be conducted to review for a newer and better option if available, in reducing pain and improving the overall experience of endodontic treatment.

Statistics suggested that 30% of patients reported significant (moderate-to-severe) pain levels. Posttreatment, only 8% indicated significant pain after 2 days. Again, this is consistent with others who have reported such a decrease in symptoms.[41] Although we used the designation of moderate-to-severe pain, most of those in the severe category would not qualify as flare-ups (postappointment emergency). It would have been interesting to compare flare-up incidences between the two groups, as was done in the Trope study.[12] However, the number of flare-ups in our patients was too low to make meaningful comparisons. That we had few flare-ups is consistent with other carefully controlled clinical studies.[42],[43]

The lacunae of available studies relevant to the research question in the endodontic literature which is an everyday practice, together with their limited sample size, is considered an obvious limitation that precluded and inspired us to conduct this meta-analysis in several instances. When performed, however, meta-analyses were often associated with substantial heterogeneity and lack of desirable studies which shared a homogenous outcome assessment. The high risk of bias in most of the included studies in this review also represents a critical limitation affecting the ability to draw valid, reliable conclusions about CH effects on pain. An important strength of this study, however, might be the ability to perform the meta-analysis to obtain pooled estimates for future recommendations.

   Conclusion Top

From this systematic review, it can be concluded that the use of calcium hydroxide as an intracanal medicament was unrelated to the incidence and severity of posttreatment pain. Calcium hydroxide is not very effective in reducing posttreatment pain when it is used alone, but its effectiveness can be increased when used in combination with other medicaments such as chlorhexidine.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

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Correspondence Address:
Dr. Sheetal Bhimrao Patekar
Department of Conservative Dentistry and Endodontics, Y. M. T Dental College and Hospital, Kharghar, Navi Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcd.jcd_501_22

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  [Figure 1], [Figure 2]

  [Table 1], [Table 2]


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