Is continuous soft chelation protocol more efficacious than conventional irrigation protocol in removing the smear layer? – A systematic review

Abstract

Introduction:

The purpose of this systematic review is to compare the effectiveness of continuous soft chelation and conventional irrigation in removing the smear layer during endodontic treatment.

Methods:

Two reviewers independently carried out an extensive literature search. Following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines; PubMed/ MEDLINE, Google Scholar, and Cochrane were searched from 2000 to 2024. In vitro studies comparing continuous and conventional chelation in smear layer removal were included. Nine studies met the criteria.

Results:

Out of 7097 articles, nine were included. Continuous chelation showed better smear layer removal in four studies, while one study favored conventional irrigation. Four studies reported similar outcomes. Etidronic acid, a soft chelating agent, was commonly used, either alone or in combination with sodium hypochlorite (NaOCl). Variations existed in protocols and outcomes. There was low-certainty evidence that continuous soft chelation protocol is better in removing the smear layer than conventional irrigation protocol. This suggests that combining a weak chelator with NaOCl solution may produce a single irrigation solution mixture that has the ability to dissolve soft tissue, has antibacterial properties, and has the ability to chelate.

Conclusion:

Hence, continuous chelation shows promise as an alternative to conventional irrigation in smear layer removal, but more research is needed to validate findings and address methodological heterogeneity.

INTRODUCTION

The smear layer is an amorphous mixture of organic and inorganic debris, microorganisms, and odontoblastic processes that forms on the root canal walls during rotary instrumentation. While there are varying opinions on whether the smear layer should be removed or retained, most studies advocate for its removal.[1] The smear layer can compromise the disinfection of the root canal system by preventing irrigants from effectively penetrating the dentinal tubules.[2,3,4] In addition, it hinders the adhesion of root canal sealers to the dentin walls, which may ultimately lead to treatment failure due to bacterial regrowth or inadequate sealing.[4]

Effective root canal preparation requires thorough chemo-mechanical debridement, which is typically achieved through the use of irrigating solutions.[5] Among these, sodium hypochlorite (NaOCl) is the most commonly used irrigant due to its ability to dissolve organic matter and its strong antibacterial properties.[6] However, NaOCl is not highly effective at removing the inorganic components of the smear layer. To address this limitation, chelating agents such as ethylene diamine tetraacetic acid (EDTA) have been introduced. EDTA works by decalcifying the dentin and removing the inorganic portion of the smear layer.[7] In practice, NaOCl and EDTA are often used together, as neither one alone meets all the ideal criteria for an endodontic irrigant.[8] However, combining the two can lead to increased dentin erosion and reduced antibacterial efficacy, as EDTA can neutralize the action of NaOCl.[9]

To overcome the drawbacks of this combination, continuous chelation was introduced by Zehnder in 2005 as an innovative approach for root canal irrigation, and the term was given by Neelakantan et al. in 2012.[10] This protocol combines a mild chelator, such as etidronic acid (HEBP), with NaOCl throughout the entire chemo-mechanical preparation process.

Continuous chelation aims to retain the antibacterial and proteolytic properties of NaOCl while simultaneously removing the smear layer in a gentler and more effective manner.[11] Other continuous chelating agents, including clodronate, tetrasodium etidronate, and Dual Rinse 1-Hydroxyethane-1,1-Diphosphonic Acid (HEDP), have also been tested in endodontics.[12] Despite the theoretical advantages of continuous chelation, evidence comparing its efficacy to conventional irrigation protocols in terms of smear layer removal remains inconsistent and conflicting.

While several studies suggest that continuous chelation offers better smear layer removal, there is a lack of systematic reviews that consolidate the evidence and compare its effectiveness directly with conventional irrigation protocols. This gap in the literature has made it difficult to establish clear clinical guidelines for the use of continuous chelation in endodontic practice. Therefore, there is a clear need for a comprehensive systematic review to evaluate the relative efficacy of continuous soft chelation compared to conventional irrigation protocols in removing the smear layer.

Given the critical role of smear layer removal in achieving a successful endodontic outcome, this systematic review aims to answer the focused research question: Is continuous soft chelation more effective than conventional irrigation protocols in removing the smear layer in extracted human permanent teeth? By synthesizing the available in vitro evidence, this review seeks to clarify the comparative effectiveness of these irrigation protocols, filling an important gap in the existing literature and providing insights to guide clinical decision-making.

MATERIALS AND METHODS

The current systematic review followed the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) following the PRISMA 2020 Checklist as shown in Table 1 and was registered in the International Prospective Register of Systematic Reviews database under number CRD42023404850.

Table 1.

Preferred reporting items for systematic review and meta-analysis checklist

PRISMA 2020 checklist
Section and topic	Item number	Checklist item	Location where item is reported
Title
Title	1	Identify the report as a systematic review	1
Abstract
Abstract	2	See the PRISMA 2020 for abstracts checklist	1
Introduction
Rationale	3	Describe the rationale for the review in the context of existing knowledge	1
Objectives	4	Provide an explicit statement of the objective(s) or question(s) the review addresses	1,2
Methods
Eligibility criteria	5	Specify the inclusion and exclusion criteria for the review and how studies were grouped for the syntheses	2
Information sources	6	Specify all databases, registers, websites, organizations, reference lists, and other sources searched or consulted to identify studies. Specify the date when each source was last searched or consulted	2
Search strategy	7	Present the full search strategies for all databases, registers, and websites, including any filters and limits used	2,4
Selection process	8	Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and, if applicable, details of automation tools used in the process	2
Data collection process	9	Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and, if applicable, details of automation tools used in the process	2
Data items	10a	List and define all outcomes for which data were sought. Specify whether all results that were compatible with each outcome domain in each study were sought (e.g., for all measures, time points, analyses), and if not, the methods used to decide which results to collect	3,4
	10b	List and define all other variables for which data were sought (e.g., participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information	3,4
Study risk of bias assessment	11	Specify the methods used to assess risk of bias in the included studies, including details of the tool (s) used, how many reviewers assessed each study, and whether they worked independently, and if applicable, details of automation tools used in the process	4
Effect measures	12	Specify for each outcome the effect measure (s) (e.g., risk ratio, mean difference) used in the synthesis or presentation of results	4
Synthesis methods	13a	Describe the processes used to decide which studies were eligible for each synthesis (e.g., tabulating the study intervention characteristics and comparing against the planned groups for each synthesis [item number 5])	2
	13b	Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions	2
	13c	Describe any methods used to tabulate or visually display results of individual studies and syntheses	2
	13d	Describe any methods used to synthesize results and provide a rationale for the choice (s). If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used	2
	13e	Describe any methods used to explore possible causes of heterogeneity among study results (e.g., subgroup analysis, meta-regression)	2
	13f	Describe any sensitivity analyses conducted to assess robustness of the synthesized results	2
Reporting bias assessment	14	Describe any methods used to assess the risk of bias due to missing results in a synthesis (arising from reporting biases)	4
Certainty assessment	15	Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome	4
Results
Study selection	16a	Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram	4
	16b	Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded	4
Study characteristics	17	Cite each included study and present its characteristics	5
Risk of bias in studies	18	Present assessments of risk of bias for each included study	5
Results of individual studies	19	For all outcomes, present, for each study: (a) Summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g., confidence/credible interval), ideally using structured tables or plots	5
Results of syntheses	20a	For each synthesis, briefly summarize the characteristics and risk of bias among contributing studies	5
	20b	Present results of all statistical syntheses conducted. If meta-analysis was done, present for each the summary estimate and its precision (e.g., confidence/credible interval) and measures of statistical heterogeneity. If comparing groups, describe the direction of the effect	5
	20c	Present results of all investigations of possible causes of heterogeneity among study results	5
	20d	Present results of all sensitivity analyses conducted to assess the robustness of the synthesized results	5
Reporting biases	21	Present assessments of risk of bias due to missing results (arising from reporting biases) for each synthesis assessed	5
Certainty of evidence	22	Present assessments of certainty (or confidence) in the body of evidence for each outcome assessed	5
Discussion
Discussion	23a	Provide a general interpretation of the results in the context of other evidence	5
	23b	Discuss any limitations of the evidence included in the review	7
	23c	Discuss any limitations of the review processes used	7
	23d	Discuss implications of the results for practice, policy, and future research	7,8
Other information
Registration and protocol	24a	Provide registration information for the review, including register name and registration number, or state that the review was not registered	2
	24b	Indicate where the review protocol can be accessed, or state that a protocol was not prepared	2
	24c	Describe and explain any amendments to information provided at registration or in the protocol	2
Support	25	Describe sources of financial or nonfinancial support for the review, and the role of the funders or sponsors in the review	8
Competing interests	26	Declare any competing interests of review authors	8
Availability of data, code, and other materials	27	Report which of the following are publicly available and where they can be found: Template data collection forms; data extracted from included studies; data used for all analyses; analytic code; any other materials used in the review	8

PRISMA: Preferred reporting items for systematic review and meta-analysis

PICO analysis

• Participant: Extracted human permanent teeth subjected to different irrigation protocols for evaluation of the amount of smear layer removed

• Intervention: Smear layer removal with continuous soft chelation protocol

• Comparison: Smear layer removal with conventional irrigation protocol

• Outcome: Amount of smear layer removed pre- and posttreatment with different irrigating protocols.

According to PICO criteria, we included articles fulfilling the following eligibility criteria.

Inclusion criteria

• In-vitro studies pertaining to the comparison between the efficacy of continuous and conventional chelation in removing the smear layer

• Articles published between the years 2000 and 2024

• Full text articles

• Original articles.

Exclusion criteria

• Case reports/series

• Randomized controlled trials

• Review articles

• Editorial letters

• Surveys

• Animal studies.

Information source

To find prospective studies for the review, a thorough literature search was done on PubMed/MEDLINE, Google Scholar, and Cochrane between the years 2000 and 2024.

Search strategy

The following keywords and Boolean Operators were used for the electronic search: (“Continuous chelation” [MeSh] AND “Smear layer” [MeSh]” OR “EDTA” [MeSh] OR “ethylenediamine tetraacetic acid” [MeSh] OR “NaOCl” [MeSh] OR “sodium hypochlorite” [MeSh] OR “etidronic acid” [MeSh] OR “etidronate” [Mesh]).

Two authors (SK and VKB) individually carried out the search and performed the data extraction. When there were disagreements, a third author (ST) came to a consensus. First, the search results’ titles were examined, and then the abstracts and those studies that were determined to be relevant to the research design were further evaluated in accordance with the eligibility criteria. The complete text was analyzed and read in cases when it was difficult to draw a conclusion from the title and abstract alone. The next step was to read the entire articles that fulfilled the PICO strategy’s eligibility criteria. The two reviewers came to an agreement on the chosen articles. When there was a disagreement, a third author (ST) came to a conclusion. Studies that met the inclusion and exclusion criteria were then evaluated qualitatively. Author(s), publication year, study design, number of teeth examined per group, continuous chelation protocol groups, conventional irrigation protocol groups, and key findings were the information that was retrieved.

Methodological risk of bias assessment

Two authors individually assessed the possibility of bias using the QUIN tool. This tool was used to evaluate the risk of bias in every individual in vitro study included in this systematic review. In case of disagreement, the third author made the final decision.

Preferred reporting items for systematic review and meta-analysis flow diagram

The flowchart of the study search strategy is shown in Figure 1.

Figure 1.

Preferred Reporting Items for Systematic Review and Meta-Analysis flow diagram

RESULTS

Study selection

A total number of 7097 articles were found from the databases (1222 articles from PubMed, 2900 articles from Google Scholar, and 2975 articles from Cochrane). Among them, 4417 articles were excluded after removing the duplicate articles using EndNote 8 software, and 365 articles were marked ineligible by automation tools, leaving 2315 articles. Out of these, 1475 articles were not included depending on the title search, 728 after abstract evaluation, and 6 articles were not retrieved. Hence, 106 articles were assessed for eligibility, out of which 97 articles were not included depending on the eligibility criteria. The reasons for exclusion were as follows: 4 articles were literature reviews, and the remaining 93 articles did not compare the amount of smear layer removed by continuous chelation and conventional irrigation protocols. Finally, nine articles were included in the current review. Differences in conventional irrigation protocols, continuous chelating agents used, and the amount of smear layer removed by different irrigating regimes are described in Table 2.

Table 2.

Characteristics of the included studies

Authors	Year of publication	Teeth evaluated (population)	Continuous chelation protocol groups (intervention)	Conventional irrigation protocol groups (comparison)	Outcome
Hegde and Thakkar[13]	2019	60 single-rooted teeth	Mixture of chloroquick low (9% HEBP and 3% NaOCl) Mixture of chloroquick high (18% HEBP and 5.25% NaOCl)	5.25% NaOCl followed by 17% EDTA	ChloroQuick high group showed better smear layer removal at the apical thirds than the conventional irrigation group
Lottanti et al.[14]	2009	51 single-rooted premolar teeth	Mixture of 1% NaOCl and 9% etidronic acid	1% NaOCl followed by 17% EDTA	Irrigation protocols employ 1% NaOCl with 17% EDTA, and a combined solution containing 1% NaOCl and 9% etidronic acid left similar amounts of smear layer on instrumented root canal walls
Patel et al.[15]	2021	30 single-rooted teeth	Mixture of 3% NaOCl and Tween Kleen	5.25% NaOCl followed by 17% EDTA	17% EDTA showed significantly lesser amounts of smear layer covering the dentinal tubules than Tween Kleen solution
Mankeliya et al.[16]	2021	60 single-rooted teeth	Mixture of 5.25% NaOCl and 18% etidronic acid	5.25% NaOCl followed by 17% EDTA	18% etidronic acid was more efficient in removing the smear layer than 17% EDTA. However, there was no statistically significant difference between them
Pandez[17]	2020	9 anterior teeth	Mixture of 5.25% NaOCl and 18% HEBP	3% NaOCl followed by 17% EDTA	17% EDTA was found to be more efficient in removing the smear layer than 18% HEBP solution
Aoun et al.[18]	2023	75 mandibular premolars	Mixture of 3% NaOCl and Rinse HEDP	3% NaOCl followed by 17% EDTA	Dual Rinse HEDP +3% NaOCl improved smear layer elimination at the apical level of the root canal
Kfir et al.[19]	2020	40 single-rooted teeth	Mixture of 3% NaOCl and Dual Rinse HEDP	3% NaOCl followed by 17% EDTA	NaOCl\HEDP was as effective as NaOCl\EDTA in removing the smear layer
Ulusoy et al.[20]	2018	144 single-rooted teeth	Mixture of 2.5% NaOCl and 9% HEBP	2.5% NaOCl followed by 17% EDTA	There was no significant difference between NaOCl and NaOCl + HEBP in terms of tissue removal
Adham et al.[21]	2022	72 maxillary molar teeth	Mixture of 3% NaOCl and 9% HEDP	3% NaOCl followed by 17% EDTA	NaOCl\HEDP was as effective as NaOCl\EDTA in removing the smear layer

HEBP/HEDP: Etidronic acid, NaOCl: Sodium hypochlorite, EDTA: Ethylenediamine tetraacetic acid

Description of the included studies

Specimens

All studies were carried out in vitro on freshly extracted human permanent teeth. Eight studies[13,14,15,16,17,18,19,20] used single-rooted teeth, either anteriors or premolars, while only one study[21] used palatal roots of maxillary molar teeth.

Conventional irrigation protocols

The chemomechanical preparation for endodontic intervention was carried out with various NaOCl concentrations with 17% EDTA: 5.25% NaOCl,[13,15,16] 1% NaOCl,[14] 3% NaOCl,[17,18,19,21] and 2.5% NaOCl.[20]

Continuous chelation protocols

Concurrent use of etidronic acid with NaOCl has been used in all the studies. Etidronic acid has been used as such in seven studies,[14,16,17,18,19,20,21] in the form of chloroquick solution in one study[13], and in the form of Twin Kleen in one study.[15]

Outcomes

Among nine selected studies, four studies[13,15,16,18] reported better smear layer removal with continuous chelation protocols, one study[17] demonstrated that conventional irrigation protocols were superior, and four studies[14,19,20,21] reported similar amounts of smear layer removal by conventional and continuous chelation irrigation methods.

Bias risk and quality assessment

The authors of the review evaluated the risk of bias for each included study and mentioned the percentages of risk of bias across all studies as given in Table 3. The investigations revealed a minimal probability of bias in all categories.

Table 3.

Risk of bias assessment

Study	Clearly Stated Aims/Objectives	Sample Size Calculation	Sampling Technique	Comparison Groups	Detailed Methodology	Operator Details	Randomization	Outcome Measurement Method	Outcome Assessor Details	Blinding	Statistical Analysis	Presentation of Results	Score	Bias Evaluation
Hedge et al13	2	2	0	2	2	0	2	1	2	1	2	2	18	75% – Low risk
Lottanti et al14	2	2	0	2	2	0	2	1	2	1	2	1	17	70.8% – Low risk
Patel et al15	2	1	0	2	2	0	2	1	2	1	2	2	17	70.8% – Low risk
Mankeliya et al16	2	2	0	2	2	0	2	1	2	1	2	2	18	75% – Low risk
Pandez et al17	2	1	0	2	2	0	2	1	2	1	2	2	17	70.8% – Low risk
Aoun et al18	2	2	0	2	1	1	2	1	2	1	2	1	17	70.8% – Low risk
Kfir et al19	2	1	0	2	1	0	2	2	2	1	2	2	17	70.8% – Low risk
Ulusoy et al20	2	2	0	2	2	0	2	1	2	1	2	1	17	70.8% – Low risk
Adham et al21	2	1	0	2	1	2	2	1	2	1	2	2	18	75% – Low risk

DISCUSSION

This systematic review aimed to compare the effectiveness of continuous soft chelation versus conventional irrigation protocols for smear layer removal in endodontics. Smear layer removal is critical for ensuring effective disinfection and facilitating the sealing of the root canal system. Given the absence of in vivo studies and randomized controlled trials on this topic, the review focused on nine in vitro studies that met specific eligibility criteria.

Chelating agents used in the studies

Among the chelating agents tested, etidronic acid was the most commonly used across the studies. It was used either as a standalone agent or in formulations such as ChloroQuick and Twin Kleen.[22,23] Etidronic acid is known for its ability to effectively remove the inorganic component of the smear layer while being biocompatible and causing fewer detrimental effects on dentin compared to stronger agents like EDTA.[13] One key advantage of etidronic acid is its ability to remain effective when combined with NaOCl, unlike EDTA, which loses its ability to dissolve tissue and form calcium complexes when mixed with NaOCl.[22]

Chloroquick, a commercial solution containing 5% NaOCl and 18% etidronic acid, has been recently introduced and is known to provide a synergistic effect in smear layer removal. Similarly, Twin Kleen is marketed as an “All-in-One Irrigating Solution,” designed for short-term compatibility with NaOCl, which helps clear debris and reduce the formation of smear layers during rotary instrumentation.[15,24]

Outcomes of smear layer removal

1. Continuous chelation protocols: Four studies[13,15,16,18] found that continuous chelation protocols were significantly more effective at removing the smear layer compared to conventional irrigation methods. This can be attributed to the prolonged presence of the chelating agent in the canal, which allows for more thorough breakdown of both organic and inorganic components of the smear layer. In these studies, the chelation process occurred throughout instrumentation, leading to superior results.[25] Additionally, the maintenance of the hypochlorite-hypochlorous acid balance in the presence of NaOCl enhanced tissue breakdown, contributing to better smear layer removal[14]

2. Conventional irrigation protocols: In contrast, one study[17] demonstrated that conventional irrigation protocols resulted in more effective smear layer removal than continuous chelation. This discrepancy could be explained by the slower, less effective action of etidronic acid and NaOCl on inorganic components of the smear layer, with full removal potentially taking up to 300 s, as indicated by Abou-Rass M et al.[26] Etidronic acid’s reduced efficacy on sclerosed dentin might also contribute to its less favorable performance in certain conditions[27]

3. Comparable results: Four studies[14,19,20,21] found no significant difference between continuous chelation and conventional irrigation protocols. These studies noted that while NaOCl retains its proteolytic and antibacterial capabilities when combined with HEBP (hydroxyethylidene diphosphonic acid), it was not a powerful enough decalcifying agent to fully replace agents like EDTA in smear layer removal.[14,28]

Challenges in smear layer removal in different canal regions

The effectiveness of smear layer removal varies across different regions of the root canal. Studies consistently found that the apical third of the root canal presents a greater challenge for smear layer removal. Due to the narrower diameter and complex anatomy of the apical third, achieving effective contact between the irrigant and the dentinal walls is difficult. This anatomical challenge results in a significant difference in smear layer removal between the apical and coronal/middle thirds of the canal, with the apical region being notably more resistant to cleaning.[29,30]

Fluid dynamics, including irrigant flow rate and the duration of contact with the canal walls, play a crucial role in the efficacy of smear layer removal. The larger canal diameters in the coronal and middle thirds allow for better irrigant flow, whereas in the apical third, reduced space limits effective irrigation and reduces the ability to remove the smear layer.[31]

Factors influencing smear layer removal

Several factors can influence the effectiveness of both continuous chelation and conventional irrigation protocols.[32,33] These include:

• Concentration and volume of chelating agents: Studies suggest that lower concentrations of etidronic acid (around 9%) are more effective and safer for smear layer removal, as higher concentrations may have negative effects on dentin integrity

• Time of contact: The duration for which the chelating agents remain in the canal significantly impacts their ability to remove the smear layer. Continuous chelation protocols benefit from prolonged contact time, which enhances their effectiveness

• Needle design and flow rate: The design of the irrigation needle and the flow rate of the irrigant can also affect smear layer removal, especially in complex canal anatomies[14]

• Activation and agitation techniques: The use of agitation devices to enhance the movement of irrigants can improve their penetration into the apical third, where smear layer removal is most difficult

• Surfactants: Surfactants, used in studies by[13,17] reduce the surface tension of irrigant solutions, improving their penetration into narrow, complex canals. This is particularly beneficial in the apical region, where proper irrigation contact is often limited.

Assessment of smear layer removal

The studies included in this review used several scoring criteria to assess smear layer removal. Commonly used scoring systems included those developed by Torabinejad et al.,[13,16] Hulsmann et al.,[19,21] and Gambarini and Laszkiewicz. However, a few studies[14,15,17,20] did not specify a standardized rating scale, which could affect the comparability of results.

Methodological quality and risk of bias

The QUIN tool was employed to assess the methodological quality and risk of bias of the included studies. This tool included 12 different parameters for this purpose. The analysis revealed a generally low risk of bias across the studies, indicating that the findings are credible and the studies adhered to rigorous methodological standards. However, due to the diversity in study designs, including variations in irrigation protocols, confounding variables, and lack of standardization, some caution is warranted when interpreting the results.

Limitations and future research

One significant limitation of this review is the heterogeneity of the studies, which prevented a meta-analysis. Additionally, most studies were conducted in teeth with relatively straight canals (curvatures of <5°), which may not accurately reflect the challenges faced when treating curved canals.

In vivo studies and long-term clinical trials are needed to validate the in vitro findings and determine how these irrigating protocols perform in more complex clinical settings, particularly in canals with severe curvatures or anatomical variations. Furthermore, factors such as blood contamination, tissue remnants, and the use of activation devices (e.g., ultrasonic or laser activation) can significantly influence the behavior of chelating agents in the root canal system. These variables should be considered in future research to better simulate real clinical conditions.

CONCLUSION

Under the considerations of this systematic review, it may be inferred that continuous chelation protocol having improved soft tissue dissolving capacity, antimicrobial properties, and chelating ability can be regarded as a potential substitute to the conventional irrigation protocol in removing the smear layer in endodontics. However, considering the high methodological heterogeneity, such conclusions are based on low certainty of evidence.

Data availability

All data generated or analysed during this study are included in this published article.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.