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. 2025 Sep 5;28(9):849–858. doi: 10.4103/JCDE.JCDE_397_25

Effectiveness of calcium hydroxide as an intracanal medicament in endodontic retreatment: A systematic review of clinical outcome

Kashmiri Chowdhury 1, S Delphine Priscilla Antony 1,✉, Pradeep Solete 1, Praveen Kumar Elango 2, Amee Sanghavi 2, Shreshtha Muskan 1
PMCID: PMC12440338  PMID: 40964636

Abstract

Introduction:

Endodontic retreatment cases are complicated by persistent biofilm-forming pathogens such as Enterococcus faecalis, as well as remnants of prior obturation material. Intracanal medicaments (ICMs), especially calcium hydroxide (Ca[OH]2), play a vital role in improving treatment outcomes through effective disinfection. This systematic review aims to assess the efficacy of Ca(OH)2 in reducing postoperative pain, microbial load, and flare-ups in retreatment cases.

Materials and Methods:

A comprehensive search strategy was conducted using four electronic databases (PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Library) to identify clinical studies from January 2005 to August 2024. Inclusion criteria focused on randomized controlled trials evaluating Ca(OH)2 alone or in combination with other medicaments or adjuncts. Risk of bias (RoB) was assessed using the Cochrane RoB 2.0 tool.

Results:

Six studies involving 430 participants were included. Four assessed postoperative pain using various scales (VAS, Numeric Rating Scale, and Verbal Rating Scale), two evaluated flare-ups, one assessed bacterial reduction, and another measured inflammatory markers. Ca(OH)2 combined with chlorhexidine (CHX) or in nanoformulations yielded improved pain control and fewer flare-ups compared to Ca(OH)2 alone. Four studies showed low RoB, while two had moderate risk.

Conclusion:

Ca(OH)2 remains a valuable ICM in endodontic retreatment. Its efficacy is enhanced when used with adjuncts such as CHX or in nanoformulations. However, the evidence is limited by heterogeneity in outcome measures and sample sizes. Further standardized, high-powered trials are warranted.

Keywords: Antibacterial, calcium hydroxide, endodontic retreatment, intracanal medicament, root canal retreatment

INTRODUCTION

Endodontic retreatment is required when initial root canal therapy fails, typically due to persistent or reintroduced bacterial infections inside the system of root canals. These recurrent infections are often difficult to eradicate because they are dominated by biofilm-forming microorganisms, particularly Enterococcus faecalis.[1,2] This pathogen, known for its resilience and ability to survive in harsh environments, poses a significant challenge in endodontic retreatment due to its capacity to enter dentinal tubules, often contributing to posttreatment apical periodontitis.[3] Retreatment cases are more complex than initial treatments, as they involve managing not only residual infection but also the remnants of previous root canal fillings and biofilms deeply entrenched in dentinal tubules.[4,5] Therefore, successful retreatment hinges on effective disinfection strategies, often combining mechanical debridement with potent Intracanal medicaments (ICMs) to guarantee that all bacteria are eradicated from the root canal system and to promote periapical healing.

Among the various ICMs available, endodontic retreatment with Ca(OH)2 has been the standard due to its antimicrobial properties and its ability to eliminate bacterial endotoxins.[6,7,8] With its high pH, calcium hydroxide creates an alkaline environment that disrupts bacterial cell membranes and denatures proteins, making it highly effective against a broad spectrum of microorganisms. However, despite these advantages, calcium hydroxide has limitations, particularly its inability to completely eradicate bacteria deep within the dentinal tubules, where resilient microorganisms such as E. faecalis and Candida albicans can persist.[9,10] This issue is compounded by the fact that calcium hydroxide’s low solubility limits its penetration into these complex anatomical spaces, such as lateral canals, reducing its overall efficacy in retreatment cases.

To overcome these challenges, combinations of Ca(OH)2 with other medicaments, such as chlorhexidine (CHX), have also been explored.[11] CHX is a potent broad-spectrum antimicrobial agent that has been shown to enhance bacterial reduction, particularly against E. faecalis[12] and C. albicans.[10] In gel form, CHX’s viscosity improves its ability to remain in the canal system and enhances mechanical cleaning, while calcium hydroxide maintains its role as a barrier material. This combination therapy has shown promising results in retreatment cases, where complete bacterial eradication is paramount for successful healing. Previous Research has indicated that the combination of CHX and calcium hydroxide offers superior synergistic outcomes compared to using either agent alone, particularly in reducing postoperative pain, flare-ups, and microbial loads.[13,14]

The ultimate goal of endodontic retreatment is to ensure complete disinfection of the canal and microbial control while minimizing complications such as postoperative pain and flare-ups, which are more common in retreatment than in primary treatment cases. Calcium hydroxide, either by itself or in conjunction with CHX, has been shown to effectively reduce these adverse outcomes by efficient disinfection and promoting tissue healing.[14] However, the success of retreatments highly depends on the precise application of these medicaments and their ability to penetrate deep into the root canal system. Recent advancements, such as nanoformulated calcium hydroxide, have shown promise in enhancing the medicament’s penetration depths and surface properties, leading to better interaction with microbial biofilms, potentially leading to improved outcomes in retreatment procedures.

This systematic review aims to evaluate the efficacy of Ca (OH) 2 as an ICM in endodontic retreatment procedures. Specifically, the review focuses on its role in reducing postoperative pain, preventing flare-ups, and enhancing microbial control. In addition, the review will explore the benefits of other ICMs, the potential synergistic effects of Ca(OH)2 in combination with other agents, such as CHX and other adjunctive therapies (lasers).

MATERIALS AND METHODS

Protocol and registration

This systematic review has been registered in the PROSPERO database (Registration Number: CRD420250651009). This article followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.[15]

Research question

Using the Population, Intervention, Comparison, Outcome (PICO) framework to form our research question, we will be answering the following:

“In endodontic retreatment patients (P), how does calcium hydroxide (I) affect pain, flare-ups, and microbial control (O) compared to adjunctive treatments or alternative medicaments? (C).”

Eligibility criteria for selection of studies

The eligibility criteria for selection of articles for the current review is: Clinical studies involving adult patients undergoing endodontic retreatment, in which calcium hydroxide (Ca(OH)2) is used as an intracanal medicament (ICM) alone and compared with Ca(OH)2-based combinations (e.g., Ca(OH)2 with chlorhexidine), other adjunctive therapies (e.g., laser disinfection), or alternative ICMs, with respect to clinical outcomes.

  1. Population: Adult participants requiring endodontic retreatment

  2. Intervention: Application of calcium hydroxide as an ICM

  3. Comparison: Calcium hydroxide combinations, adjunctive therapies, and alternative ICMs or placebo

  4. Outcomes: Postoperative pain, bacterial reduction, incidence of flare-ups, and clinical success rates.

Search strategy

A thorough search of the existing literature was performed using several electronic databases, including PubMed (Medline), Scopus, Web of Science, and the Cochrane Library. The search covered studies published in the English language between January 2005 and August 2024, those which were categorized as endodontic retreatment cases, randomized controlled trials, and using calcium hydroxide as an ICM.

The following keywords were used to develop a comprehensive search strategy: “calcium hydroxide,” “endodontic retreatment,” “ICMs,” “postoperative pain,” “bacterial reduction,” and “flare-up.” Boolean operators, such as the search terms, were successfully combined by using AND and OR.

Studies focusing on in vitro models, nonhuman subjects, or nonpeer-reviewed theses were excluded from the above search. In addition, references of relevant studies were examined using the snowballing method to ensure no important studies were missed. The full search strategy and keyword combinations are detailed, as shown in Table 1.

Table 1.

Search terms

Search engine Keywords
MedLine via PubMed (“Endodontic retreatment” OR “Root canal retreatment” OR “Secondary endodontic treatment” OR “Endodontic failure”) AND (“Calcium hydroxide” OR “Ca(OH)2” OR “Intracanal calcium hydroxide”) AND (“Chlorhexidine” OR “Iodine” OR “Triple antibiotic paste” OR “Formocresol” OR “Sodium hypochlorite” OR “EDTA”) AND (“Postoperative pain” OR “Flare-ups” OR “Microbial control” OR “Bacterial reduction” OR “Periapical healing” OR “Treatment outcome”) AND (“Randomized controlled trial” OR “Clinical trial” OR “Prospective study” OR “Retrospective study”)
Web of Science TS=(“Endodontic retreatment” OR “Root canal retreatment” OR “Secondary endodontic treatment” OR “Endodontic failure”) AND TS=(“Calcium hydroxide” OR “Ca(OH)2” OR “Intracanal calcium hydroxide”) AND TS=(“Chlorhexidine” OR “Iodine” OR “Triple antibiotic paste” OR “Formocresol” OR “Sodium hypochlorite” OR “EDTA”) AND TS=(“Postoperative pain” OR “Flare-ups” OR “Microbial control” OR “Bacterial reduction” OR “Periapical healing” OR “Treatment outcome”) AND TS=(“Randomized controlled trial” OR “Clinical trial” OR “Prospective study” OR “Retrospective study”)
Scopus TITLE-ABS-KEY (“Endodontic retreatment” OR “Root canal retreatment” OR “Secondary endodontic treatment” OR “Endodontic failure”) AND TITLE-ABS-KEY (“Calcium hydroxide” OR “Ca(OH)2” OR “Intracanal calcium hydroxide”) AND TITLE-ABS-KEY (“Chlorhexidine” OR “Iodine” OR “Triple antibiotic paste” OR “Formocresol” OR “Sodium hypochlorite” OR “EDTA”) AND TITLE-ABS-KEY (“Postoperative pain” OR “Flare-ups” OR “Microbial control” OR “Bacterial reduction” OR “Periapical healing” OR “Treatment outcome”) AND TITLE-ABS-KEY (“Randomized controlled trial” OR “Clinical trial” OR “Prospective study” OR “Retrospective study”)
Cochrane library (Endodontic retreatment OR “Root canal retreatment” OR “Secondary endodontic treatment” OR “Endodontic failure”) AND (Calcium hydroxide OR “Ca(OH)2” OR “Intracanal calcium hydroxide”) AND (Chlorhexidine OR Iodine OR “Triple antibiotic paste” OR Formocresol OR “Sodium hypochlorite” OR EDTA) AND (“Postoperative pain” OR “Flare-ups” OR “Microbial control” OR “Bacterial reduction” OR “Periapical healing” OR “Treatment outcome”) AND (“Randomized controlled trial” OR “Clinical trial” OR “Prospective study” OR “Retrospective study”)
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Study selection and identification

After removing duplicates using Rayyan, two reviewers checked the identified records’ titles and abstracts for relevancy. Studies that met the inclusion criteria based on the PICO framework were retrieved in full text for further evaluation. Any inconsistency between the reviewers was resolved through discussion, and when necessary, a third reviewer was consulted to reach a consensus.

Data extraction and quality assessment

Data extraction was performed by two independent reviewers from the studies included by using a predesigned data extraction form. The extracted data included study design, sample size, intervention groups, outcomes assessed, duration of follow-up, blinding, retention rates, limitations, and results. In case of disagreements, a third reviewer was consulted in the data extraction process to make a final decision. Inter-rater reliability (IRR) was assessed using Cohen’s kappa, indicating substantial agreement (k = 0.76) between the two screening reviewers. This shows the screening process was done in a consistent and similar manner, suggesting a robust and reproducible decision-making (k) Cohen’s kappa formula is: κ = 1 − PePo − Pe, κ ≈ 0.76.

Risk of bias assessment

The quality of the included studies was assessed using the Cochrane Risk of Bias tool (RoB 2.0) for randomized controlled trials.[16] The RoB assessment was performed for all studies with the five key constructs being evaluated: bias arising from the randomization process, bias due to deviations from intended interventions, missing outcome data, RoB in measurement of the outcome, and RoB in selection of the reported result. The overall rating of each construct was classified as “low risk,” “high risk,” or “some concerns.” Two independent reviewers performed the RoB assessment, resolving conflicts through discussion or by consulting a third reviewer. If additional information was required, study authors were contacted via email for clarification.

Randomization protocol

All included studies were randomized controlled trials (RCTs), with random allocation sequences generated using computerized random number generators or random allocation software. Allocation concealment was described in four studies through the use of sealed opaque envelopes or third-party allocation. Two studies did not clearly describe the randomization process and were thus assessed as having “some concerns” under the randomization bias domain. None of the studies reported baseline imbalances, and most ensured equal distribution of confounding variables through proper random sequence generation and allocation methods.

RESULTS

Search and study selection

A total of 1797 articles were retrieved from 4 databases. After removal of 59 duplicate articles and 901 ineligible articles, 819 articles were screened for their title and abstract. The full-text eligibility of the articles was evaluated, and finally, 6 articles were included in this systematic review [Figure 1].

Figure 1.

Figure 1

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Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart of included studies

Characteristics of included studies

The characteristics of the included studies have been summarized in Table 2. This systematic review comprises studies that required endodontic retreatment due to failed primary root canal therapy, presenting as apical periodontitis, periapical lesions, or recurrent pain. A total of six randomized control trials, all published in the English language, with 430 systemically healthy participants were enrolled in the included studies. Except for one trial that was conducted in a private dental clinic, all the other RCTs were conducted in a university setting.[17] All included studies followed a two-visit endodontic retreatment protocol except for one, which compared a single-visit protocol without ICM to multiple visit retreatment protocols with ICM.[18] For the present review, the efficacy of Ca(OH)2 as an ICM in comparison to its various combinations, other ICMs, and different adjunctive therapeutic modalities is of interest. In all the studies, ICMs were placed for 7 days, except for one where calcium hydroxide was placed for 10 days.[17] Six different comparison groups were identified: no ICM, CHX, Ca(OH)2 + CHX, Nano-silver, Nano-Ca(OH)2 , and Ca(OH)2 + Laser Irradiation. Four articles reported postoperative pain assessment using either the Verbal Rating Scale, Numeric Rating Scale (NRS), or the Visual Analog Scale (VAS), across different time points.[18,19,20] Two studies evaluated the incidence of flare-ups.[20,21] One study assessed the reduction in bacterial count before and after placement of ICM,[20] while another assessed the levels of inflammatory markers.[22] Finally, one study assessed periapical healing after endodontic retreatment at 3 and 6 months.[17]

Table 2.

Characteristics table of included studies

Author name Year Country Study design Study setting Sample size Sample characteristics Tooth type Number of visits Intervention groups
Erdem Hepsenoglu et al.[18] 2018 Istanbul, Turkey RCT University dental clinic 150 Systemically healthy, patients needing nonsurgical retreatment without pain 150 teeth in 150 patients Single and multi-rooted teeth Single and multiple visits Group 1: Single-visit retreatment (n=50) Group 2: Multiple-visit retreatment with the interappointment application of Ca(OH)2 (n=50) Group 3: Multiple visit retreatment with the interappointment application of CHX gel (n=50)
Angın et al.[19] 2024 Aydin, Turkey RCT University Dental Clinic 108 Systemically healthy, patients with posttreatment apical periodontitis Single root and single-canal incisor, canine, premolar teeth 2 visits Group 1: Ca(OH)2 (n=39) Group 2: CHX (n=39) Group 3: Combination (n=39)
Fahim et al.[20] 2022 Cairo, Egypt RCT University dental clinic 69 Systemically healthy, posttreatment disease Single root teeth 2 visits Group 1: Nano-silver (n=23) Group 2: nano-Ca(OH)2 (n=23) Group 3: CH (n=23)
Noferesti et al.[17] 2024 Birjand, Iran RCT Private dental clinic 19 Systemically healthy Endodontic retreatment with periapical lesions or presence of apical periodontitis 24 teeth in 19 patients Single root teeth 2 visits Group 1: Ca(OH)2 (n=11) Group 2: Ca(OH)2 + laser irradiation (n=8)
Özdemir et al.[22] 2019 Erzurum, Turkey RCT University Dental Clinic 60 Systemically healthy, patients with apical periodontitis and failed primary treatment No information 2 visits Group 1: CH (n=30) Group 2: CHX gel (n=30)
Hussein and Sherif Elkhodary[21] 2019 Cairo, Egypt RCT University Dental Clinic 24 Patients requiring two-visit endodontic retreatment procedures Single and multi-root teeth 2 visits Group 1: GH + CHX combination Group 2: Ca(OH)2
Author name Duration of ICM Outcomes assessed using Duration of assessment Blinding Follow-up and retention Limitations Results obtained
Erdem Hepsenoglu et al.[18] Group 1: 7 days Group 2: 7 days Group 3: 7 days Postoperative pain using VRS after obturation 1,2,3,7, and 30 days Single-blind 100% retention No molecular microbiology for bacteria analysis CHX group reported more moderate-severe pain than CH group
Angın et al.[19] Group 1: 7 days Group 2: 7 days Group 3: 7 days Postoperative pain was evaluated at 6 h, 12 h, 1,2,3,4,5,6,7 days with VAS for pain levels after ICM placement Oral examination performed at 48 h and 7th day 7 days Single-blind 90% retention Limited to single-rooted teeth, short assessment period Ca(OH)2 had the lowest postoperative pain in the first 24 h No significant difference in VAS scores across groups; low flare-up rate (1 patient)
Fahim et al.[20] Group 1: 7 days Group 2: 7 days Group 3: 7 days Antibacterial effect (primary outcome) Bacterial count reduction Flare-ups, postoperative pain 6, 12, 24, 48 and 72 h after first visit (secondary outcome) using the NRS scale For bacterial count: 3 samples taken between 2 sessions For pain and flare up: 6, 12, 24, 48 and 72 h after first visit 1 week Double-blind All patients included in final analysis Short follow-up period, no long-term microbial assessment Antibacterial effect: Reduction in bacterial count, Enterococcus faecalis count and biofilm formation after cleaning and shaping as well as ICM application The highest incidence of flare ups was seen with CH as an ICM. Nano-based medicaments had similar antibacterial effects to CH, superior in controlling postoperative pain
Noferesti et al.[17] Group 1: 10 days Group 2: 10 days followed by LI Periapical lesion healing assessed by radiographs 3 months and 6 months Double-blind All patients included in final analysis Small sample size, lack of long-term follow-up In both groups, periapical healing after 6 months improved more than at 3 months Longer follow-up periods is necessary No statistically significant difference between the two groups at 3 and 6 months
Özdemir et al.[22] Group 1: 7 days Group 2: 7 days VIP, MMP-9 levels in periapical lesions 7 days, 12 months Not stated All patients included in the final analysis No molecular microbiological analysis CH increased VIP levels; CHX increased MMP-9 levels
Hussein and Sherif Elkhodary[21] Group 1: 7 days Group 2: 7 days Postoperative flare-up incidence after application of ICM, clinical pain scores (VAS) 6 h, 12 h, 24 h, 48 h, 72 h, and 7 days preobturation Single-blind All patients included in final analysis Limited to short-term follow-up The CH + CHX group had lower rates of postoperative flare-up and reduced pain levels compared to the CH group
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VRS: Verbal rating scale, VAS: Visual Analog Scale, Ca(OH)2: Calcium hydroxide, VIP: Vasoactive intestinal peptide, MMP-9: Matrix metalloproteinase-9, CHX: Chlorhexidine, RCT: Randomized controlled trials, ICM: Intracanal medicament

Risk of bias assessment

The RoB assessment for the included studies is presented in Table 3. Four of the six studies reported a low overall RoB, whereas two studies reported a moderate RoB, highlighting the strong methodology of the studies included in Figure 2 and 3.[17,18,19,20] Of the four studies evaluating postoperative pain, three displayed an overall low RoB,[18,19,20] while the fourth one demonstrated an overall moderate RoB,[21] primarily due to a moderate RoB in outcome measurement and deviations from intended intervention domains. Two studies evaluated flare-up incidence, one reported an overall low risk[20] and the other reported an overall moderate RoB due to a moderate RoB in outcome measurement and deviations from intended intervention domains.[21] One study measuring the inflammatory marker levels (vasoactive intestinal peptide [VIP] and matrix metalloproteinase-9 [MMP-9]) in periapical lesions reported an overall moderate RoB due to a moderate possibility of prejudice in the outcome measurement and in the selection of reporting results domains. Finally, the two studies measuring antibacterial reduction and periapical healing, respectively, reported an overall low RoB.[17,20]

Table 3.

Risk of bias assessment (risk of bias 2 tool)

Study D1: Bias due to randomization D2: Bias due to deviations from intended intervention D3: Bias due to missing data D4: Bias due to outcome measurement D5: Bias due to selection of reported result Overall RoB
Erdem Hepsenoglu et al.[18] Low Low Low Low Low Low
Angın et al.[19] Low Low Low Low Low Low
Fahim et al.[20] Low Low Low Low Low Low
Noferesti et al.[17] Low Low Low Low Low Low
Mine Büker Özdemir (2018)[22] Low Low Low Moderate Moderate Moderate
Hussein et al. (2019)[21] Low Moderate Low Moderate Low Moderate
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Hepsenoglu et al.[18] (2018), Angın et al.[19] (2024), Fahim MM et al. (2022), and Noferesti et al.[17](2024) studies demonstrate a low risk of bias, with well-executed randomization and blinding. Özdemir MB et al.[22] faces moderate risk of bias due to unclear blinding and possible selective reporting of biochemical markers. Hussein et al. (2019)[21] show moderate risk of bias, primarily due to lack of randomization, control group, and inconsistent outcome measurement

Figure 2.

Figure 2

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Risk of bias of included studies

Figure 3.

Figure 3

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Risk of bias (RoB) of the included studies (a) RoB, (b) Distribution of the RoB across domains

Outcomes measured

Postoperative pain

Four studies investigated postoperative pain in different ICMs and treatment protocols. Erdem Hepsenoglu et al. observed that postoperative pain was greater in women under 45 years old and in teeth with preoperative pain, as well as in those with short root fillings. In addition, the study highlighted that single-visit treatments led to significantly less pain compared to multiple visit treatments with ICM placement.[18] When comparing Ca(OH)2 , CHX, and its combination, The VAS scores for the three groups did not differ statistically significantly at any of the time points (P > 0.05). In addition, patients without a fistula experienced significantly greater pain in comparison to patients with a fistula. However, it is important to mention that the Ca (OH) 2 group had the lowest VAS scores during the first 24 h postoperatively, with the pain levels fluctuating up to the 7th day. In contrast, the Ca(OH)2 + CHX gel group exhibited higher VAS scores at 12 h but showed a continuous decline, reaching the least VAS score at 48 h in comparison to the other groups. The CHX gel group consistently reported higher pain levels than the other groups.[19] Fahim et al. reported significant pain reduction at 48 and 72 h after the application of nano-Ag and nano-Ca(OH)2.[20] Lastly, Hussein and Sherif Elkhodary reported that a combination of Ca(OH)2 and CHX resulted in significantly less pain than Ca(OH)2 alone after 6 h, with no significant differences at later time points.[21]

Flare-up

Along with postoperative pain and bacterial count, Fahim et al. also reported on the incidence of flare-ups, which was defined as “the development of swelling or the occurrence of severe pain (NRS ≥7) after the first visit.” In this study, most of flare-ups were observed with Ca(OH)2 ICM (3 cases), while only one case of flare-up was observed with either the nano-Ag or nano-Ca(OH)2 ICM.[20] Another study evaluating postoperative pain also described a flare-up as severe pain with or without a swelling, and assessment was performed at multiple time points – 6 h, 12 h, 24 h, 48 h, 72 h, and 7 days after the preobturation appointment. However, no statistically significant difference was found in the incidence of swelling between the two groups.[21]

Reduction in bacterial count

Along with postoperative pain and flare-up assessment, Fahim et al. also assessed the antimicrobial efficacy of nano-Ag, nano-Ca(OH)2, and Ca(OH)2 by assessing the reduction in E. faecalis and total bacterial counts, as well as the capacity to form biofilms of the remaining microbiota. Three microbial samples were collected during the treatment: Following the removal of the old canal filling, the first sample (S1) containing the original microorganisms was obtained. The second sample (S2) was taken after chemomechanical debridement before application of the ICM, and the final sample (S3) was collected 7 days later, after the removal of the ICM. The study reported a decrease in the overall number of bacteria, total E. faecalis count, as well as the biofilm-forming capacity of the remaining microorganisms, with the antimicrobial activity being prominent after the chemomechanical preparation in comparison to after ICM application. Nevertheless, no statistically significant variations were observed between nano-Ag, nano-Ca(OH)2, and Ca(OH)2 groups.[20]

Inflammatory markers

Interestingly, the study by Özdemir et al. assessed MMP-9 and VIP levels in periapical lesions after placement of Ca(OH)2 and CHX gel as an ICM. Both MMP-9 and VIP are considered as potent inflammatory mediators which may contribute to posttreatment flare-up. The results demonstrated that Ca(OH)2 does not increase the level of MMP-9 postoperatively but increases the VIP levels (P < 0.05). Conversely, CHX causes significant increase in MMP-9 levels without any significant change to the VIP levels.[22]

Periapical healing

Noferesti et al. assessed the effectiveness of Ca(OH)2 alone or in combination with 980 nm diode laser irradiation as an ICM by evaluating periapical radiographic healing before endodontic retreatment and at 3-month and 6-month follow-up appointments. It was observed that both Ca(OH)2 alone or in combination with laser irradiation improve periapical healing at the 6-month follow-up in comparison to the 3-month follow-up appointment. However, there was no statistically significant difference in the healing of the periapical lesions between the two groups after endodontic retreatment.[17]

DISCUSSION

This systematic review aims to assess the efficacy of Ca(OH)2 as an ICM in comparison to other therapeutic modalities in endodontic retreatment, focusing on clinical outcomes such as postoperative pain, incidence of flare-ups, bacterial count reduction, inflammatory marker levels, and progress in periapical healing. The review searched four electronic databases using a combination of free-text and controlled-vocabulary terms with an English language filter. Data extraction, RoB assessment, and identification of the included studies were all carried out independently by two reviewers. Inclusion criteria were specific to consider only retreatment cases using Ca(OH)2 as an ICM. IRR measures using Cohen’s kappa indicate substantial agreement (k = 0.76) between the two screening reviewers. This indicates the screening process was done in a consistent and similar manner, suggesting a robust and reproducible decision-making. The final review included six randomized controlled trials (RCTs) with a total of 430 participants, all of whom underwent endodontic retreatment following failed primary root canal therapy. However, due to the high degree of heterogeneity among the included articles and an overall moderate RoB in two of the studies, no pooled analysis was carried out. In addition, only two studies, Erdem Hepsenoglu et al. and Angın et al.,[18,19] had an adequate sample size of 100 or more participants, while the remaining studies[17,20,21,22] lacked sufficient power to detect significant outcomes [Figure 4]. Variability in outcome assessment tools further contributed to the observed heterogeneity. Despite these limitations, the review offers valuable insights into the clinical performance of Ca(OH)2 as an ICM, providing evidence that may aid clinicians in selecting the most appropriate ICM for successful endodontic retreatment.

Figure 4.

Figure 4

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Bar graph representing the sample size of the included studies

Postoperative pain was the most common clinical outcome measured, with four studies reporting pain at different time intervals. Erdem Hepsenoglu et al. reported higher incidence of postoperative pain in females and participants below 45 years of age,[18] while Angin et al. reported a similar age-related increased incidence of postoperative pain in participants between 35 and 49 years of age.[19] However, our findings are in contrast with a previous systematic review, which reported that age or the process of ageing does not impact the success of endodontic treatment.[24] Additionally, four out of six studies also reported using CHX as an ICM either alone or in combination with Ca (OH)2 to assess its potential as an ICM in comparison to Ca(OH)2 alone.[18,19,22,23] Both Hussein et al. and Angin et al. reported that the Ca(OH)2-CHX combination demonstrated superior properties as an ICM but exhibited lower pain reduction within the first 24 h.[19,21] Beyond this period, the groups’ pain scores did not differ in a way that was statistically significant.

Two studies[20,21] evaluated the incidence of flare-ups (characterized as a sudden onset of severe pain with or without the presence of swelling) at multiple timepoints: 6, 12, 24, 48, 72 h, and after 1 week. Fahim et al. reported an increased incidence of flare-ups (13%) after application of Ca(OH)2 as an ICM in comparison to nano-Ag or nano-Ca(OH)2 (4.2%).[20] Previous studies have found that nano-Ag gel used as an ICM in concentrations of 0.1% and 0.2% is more effective than CHX, camphorated phenol, and Ca(OH)2.[25,26] In addition, Fahim et al. reported a reduction in total microbial count, E. faecalis count, and biofilm-forming capacity.[20] This could be attributed to the increased surface area of the nanoparticles, which enhances their antimicrobial effect. The nanoparticles damage the bacterial cell membrane by targeting sulfur-containing proteins and DNA phosphates, thereby reducing the risk of postoperative complications.[27] Nano-based calcium hydroxide (Ca(OH)2) cements have demonstrated promising antibacterial efficacy against Enterococcus faecalis, even at high pH levels—an environment where conventional Ca(OH)2 typically shows reduced effectiveness.[28] Similarly, Hussein and Sherif Elkhodary reported lower incidence of flare-ups in participants with Ca(OH)2-CHX as an ICM.[21] CHX Chlorhexidine (CHX) is commonly used in endodontics as an ICM due to its broad antimicrobial activity, substantivity, low cytotoxicity, lubricating properties, chemical stability, water-solubility, and ability to inhibit metalloproteinase.[28] It has been hypothesized that a combination of CHX-Ca(OH)2 could offer excellent antimicrobial properties and greater clinical success as an ICM.

Persistent periapical infection after primary root canal therapy triggers the release of inflammatory mediators such as cytokines, prostaglandins, and proteolytic enzymes into the periapical area.[29] These inflammatory mediators result in severe pain and swelling; most often, patients require endodontic retreatment. In the current review, one study evaluating inflammatory mediators proposed that the type of medication may have an impact on the levels of inflammatory markers. A study conducted by Özdemir MB et al.[22] reported that participants who received calcium hydroxide (Ca(OH)2) as the intracanal medicament (ICM) showed increased post-treatment levels of vasoactive intestinal peptide (VIP), whereas those in the chlorhexidine (CHX) group exhibited elevated matrix metalloproteinase-9 (MMP-9) levels after treatment.[23] VIP expression levels have been found to inversely correlate with the diameter of chronic periapical lesions, with higher VIP levels observed in smaller lesions.[30] The capacity of Ca(OH)2 to inhibit osteoclast-like cell differentiation may promote lesion healing, potentially contributing to the increased VIP levels.[31] In addition, Ca(OH)2 stimulates expression of Th-2 type cytokine levels, which increases VIP levels.[32,33] The CHX (pH between 5 and 7) group exhibited increased posttreatment MMP-9 levels possibly due to its limited effectiveness against the lipopolysaccharide (LPS) of pathogenic bacteria.[34,35] The neutral pH of CHX, along with its limited impact on LPS, may have created a more acidic environment in the periapical region, leading to increased MMP-9 levels.

Calcium hydroxide (Ca(OH)2) is widely used as an ICM in endodontic retreatment due to its strong alkalinity, effective antimicrobial properties, and ability to promote periapical healing. However, its effectiveness in alleviating pain during retreatment remains inconsistent, suggesting it may vary depending on individual cases and clinical context.[36,37] Anjaneyulu and Nivedhitha assessed several trials and reported that Ca (OH) 2 does not provide reliable and consistent positive postoperative outcomes.[27] The present study focuses on the importance of various ICMs for endodontic retreatment, offering insights into their clinical efficacy in managing key outcomes such as postoperative pain, microbial reduction, flare-ups, and periapical healing. Our findings align with prior studies suggesting that a combination of Ca (OH) 2 and CHX can be particularly effective in reducing the postoperative complications associated with endodontic therapy.[27,28,38] A systematic review by Manobharathi et al. provides clinicians with evidence-based insights to support the selection of optimal strategies for endodontic retreatment, ultimately contributing to improved patient care and treatment success.[39] To guide endodontic retreatment decisions effectively, future research should incorporate larger study populations and outcomes of clinical relevance.[40] This review aims to help clinicians make informed decisions on the most appropriate ICM to use, tailored to the patient’s individual needs and the complexity of the case.

CONCLUSION

While Ca(OH)2 remains a cornerstone in endodontic retreatment, its effectiveness can be enhanced when used in combination with other ICMs such as CHX, as well as adjunctive therapeutic modalities. To optimize clinical outcomes and improve patient care, it is important to consider various treatment options. In the present review, the heterogeneity and inconsistency of results, largely due to the lack of standardized outcome measures, highlight the need for cautious interpretation. The limited evidence currently available emphasizes the necessity for more larger sample sizes in randomized controlled trials, uniform assessment tools, and robust methodologies to establish definitive, evidence-based treatment guidelines.

Authors’ contribution statement

Chowdhury K. developed the concept and methodology, carried out the search plan, assisted with data extraction, and wrote the manuscript. Antony DP came up with the concept and methodology, carried out the search plan, helped with data extraction, and wrote the manuscript. Pradeep S. developed the concept and methodology, carried out the search plan, helped with data extraction, and wrote the manuscript. Elango PK helped with the data extraction and analysis, the manuscript’s drafting and critical revision, and its writing and review. Sanghavi A contributed to data extraction and analysis, interpretation, drafted, and critically revised the manuscript. Muskan S contributed to data extraction and analysis and interpretation and drafted and critically revised the manuscript.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.

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