Comparison of Sodium Hypochlorite and Chlorhexidine Gluconate: Quality of Current EvidenceVolume 19, Issue 4 on 29 September 2008Elaine DangUniversity of California, Los AngelesAbstractSuccessful endodontic treatment involves removal of necrotic tissue, bacterial infiltrates, and accumulatedprocedural debris. However, available irrigants may potentially cause postoperative pain which results indiscomfort for the patients. This study aims to evaluate the quality of the current evidences that comparedthe mildness and antimicrobial activities of the most widely used endodontic irrigants: sodiumhypochlorite and chlorhexidine gluconate. A Timmer analysis is performed in developing a best baseseries relevant to antibacterial effects of these two root canal irrigants. The research question for thisstudy is stated as: “Will sodium hypochlorite compared to chlorhexidine reduce Entrococcus faecalisbacterial counts in the root canal space?” A comprehensive search of the literature was done throughMedline using the flowing keywords: sodium hypochlorite, chlorhexidine gluconate, root canal irrigant,Entrococcus faecalis, anti-microbial activities, and toxicity. The results of this study shows that the bestcurrent evidence is that of an randomized, in vitro design which implies that an in vivo design and/orimproved research methods need to be conducted in order to improve the current evidence.IntroductionNumerous bacteria colonize the root canal space including Fusobacterium nucleatum, Eubacteriumalactolyticum, E. nodatum, Lactobacillus casei, and Peptostreptococcus micros. Upon infection, the mostcommon bacterial infiltrate is Enterococcus faecalis (E. faecalis). Endodontic procedures, or root canaltherapy, are performed to treat the infection and seal the tooth against re-infection. Successful endodontictreatement involves removal of necrotic tissue, bacterial infiltrates, and accumulated procedural debris.Root canal irrigants, used in endodontic procedures, include camphorated monchlorophenol,ethylenediaminetetraacetic acid (EDTA), formocresol, hydrogen peroxide, metacresylacetate, and sodiumhypochlorite. Sodium hypochlorite (NaOCl) is the preferred irrigant to disinfect and remove proceduraldebris from the root canal space. NaOCl, however, has an unpleasant taste, is toxic in highconcentrations, and has a limited bactericidal spectrum. Recently, chlorhexidine gluconate (CHX) hasbeen introduced as a root canal irrigant. Compared to NaOCl, CHX is effective against E. faecalis, activepostoperatively for up to 72 hours. These irrigants, however, may cause postoperative pain. Thus, rootcanal debridement requires an irrigant that demonstrates maximum bactericidal and cleansing activities.An irrigant must also reduce patient discomfort by minimizing tissue toxicity and inflammation.The purpose of this study is to establish an acceptance score for a best case series in determining theantibacterial effects of two root canal irrigants: 5.25% sodium hypochlorite compared to 2%chlorhexidine gluconate. The findings are used to discuss the quality of evidence currently available for asubsequent systematic review.MethodsPICO AnalysisPICO is an abbreviation for population (P), intervention (I), comparison (C), and outcome (O). Thisanalysis includes the population studied, the interventions that are compared, and the outcome that is tobe measured. For this research question, the population is inclusive of those studies that used human teeth
as their samples, compared the interventions sodium hypochlorite to chlorohexidine gluconate, andmeasured of E. faecalis bacterial counts as the outcome.Gathering EvidenceA comprehensive search of the literature was done to compile a case series relevant to the researchquestion. A search of PubMed (NCBI, National Library of Medicine) online database, Medline, and theBritish Journal of Dentistry was performed using the following keywords: sodium hypochlorite,chlorhexidine gluconate, root canal, E. faecalis, and anti-microbial activities. The acquired abstracts werefiltered using inclusion and exclusion criteria (Table 1).The inclusion criteria included those abstracts that used human teeth to compare the bactericidal, or anti-bacterial, activity of sodium hypochlorite to chlorhexidine gluconate. Antimicrobial activity was limitedto measuring the reduction of E. faecalis counts. The exclusion criteria removed from the analysis thoseabstracts that used animal teeth to study other anti-bacterial or non-antibacterial irrigants, in reducingother bacteria infiltrates found in the root canal spaces. Also excluded were predictions that provided theprobability of one or other interventions in reducing E. faecalis counts. From this process, an initial caseseries of abstracts was obtained. For the initial case series, a Timmer analysis (Timmer et.al., 2003) wasperformed to develop the best case series for a subsequent systematic review.Table 1. Inclusion and Exclusion Selectrion Criteria: These are the criteria used to select appropriateabstracts to answer the topic of interest. This analysis includes the population studied, the interventionsthat are compared, and the outcome that is to be measuredTimmer AnalysisThe Timmer analysis consists of the Quality Assessment (QAS; Table 2), Study Design (SDS; Table 3)and Summary scores. The calculation of the QAS is accomplished for each abstract of the initial caseseries. The QAS instrument contains 19 items. The abstract is scored by each item according to if the itemhas been fully met: yes for 2 points, partial for 1 point, no for 0 points, and not applicable (N/A) for -2points. The QAS is determined by the sum of all assigned points. The maximum QAS is 38 points. TheSDS is determined by the type of study design with an additional point given if the study is randomized.The maximum SDS is 5 points for a randomized, human intervention study, or randomized clinical trial.Other study design categories will have a lesser maximum SDS. Thus, the highest scoring abstract, arandomized clinical trial, is awarded a QAS of 38 points and a SDS of 5 points for a total score of 43points. The Summary score (Figure 1) is a ratio of the awarded score (QAS + SDS) to the maximumpossible points. The maximum possible points are again dependent on the individual study’s designcategory. For example, the maximum possible points for a randomized clinical trial study design are 43points. Other study design categories will have a lesser maximum possible points. Thus, the randomizedclinical trial will have a Summary score of 1 and gives the highest level of evidence. Abstracts with alower Summary score than 1 in their study design category indicates a study whose findings are lessrigorous and subject to more variation. For all abstracts analyzed in this study, however, the denominatorfor calculation of the Summary score was chosen to be equivalent to the highest design category. Thus, allabstracts in the initial case series were analyzed against the highest level of evidence, the randomizedclinical trial study design.
Figure 1. Calculation of Summary Score: Summary Score of each abstract is calculated as the sum of theQuality Assessment Score (QAS) and the Study Design Score (SDS) divided by the total possible scoreTable 2. Quality Assessment Score (QAS): Each abstract is rated based on the Quality Assessment Test.The QAS instrument contains 19 items. The abstract is scored by each item according to if the item hasbeen fully met: yes for 2 points, partial for 1 point, no for 0 points, and not applicable (N/A) for -2 points.The QAS is determined by the sum of all assigned points. The maximum QAS is 38 points
Table 3. Study Design Score Sheet: This sheet contains summary of all the accepted study designs and thetype of designs each employed to complete the research. The maximum SDS is 5 points for a randomized,human intervention study, or randomized clinical trialAcceptance ScoreThe Acceptance score was arrived at by determining the average between the lowest and highest Timmerscores. The difference between these scores was divided by 2. The result was subtracted from the highestTimmer score to give the initial cut-off point in determining the Acceptance score. The initial cut-offpoint provided a threshold in separating acceptable from unacceptable research designs based on amidpoint of calculated scores. The research design attributes or characteristics were then analyzed. Anevaluation was made to determine if the initial cut-off point produced an Acceptance score that stillincluded unacceptable designs in comparison with that of the abstract with the highest Timmer score. Ifthe initial cut-off point did so, then the cut-off point analysis was performed again. This process producedthe final Acceptance score for acceptable research designs in producing best evidence from availableresearch designs acquired at this time.ResultsFiltering unacceptable designsThe initial case series consisted of eight abstracts (Table 4)
Table 4. Summary scores for selected case series: Table summarizes the score for each selected caseseries and also lists the methods each research used. The research designs for the initial case series included in vitro and randomized in vitro studies. Foreach abstract, the research design describes its ranking on the hierarchical scale of acceptable designs(Figure 2)Figure 2. Evidence Pyramid: The pyramid shows the different types of materials used in a research withthe least clinically relevant at the bottom and the most clinically relevant at the top. The four layers at thetop represent actual clinical research whereas the layers at the bottom are not as clinically relevant butcan be used as guides in the initial research stages. From the Timmer analysis, the Summary score for each abstract of the initial case series ranged from49% to 65%. The final cut-off point, and thus the Acceptance score, was determined to be 57%. However,Abstract 8 lacked randomization and was excluded from the best case series. Thus, the best case seriesincluded 2 abstracts with Summary scores ranging from 60% to 65% (Table 5)
Table 5. Summary scores for best-case series: Two best case series are selected based on the scores theyreceived and the research designs employed. The research designs of these accepted abstracts differed from the unacceptable designs in severalrespects.Lack of randomization and statistical testsOf the abstracts with unacceptable designs, Abstracts 1, 3, and 8 lacked randomization. Randomizationassures that each tooth has an equal and independent chance of being assigned to either irrigant testgroups. Random allocation minimizes differences in tooth characteristics between the test groups andincreases the reliability of the results. While Abstracts 1 and 3 described their findings, abstract 8 usedappropriate statistical tests in reporting findings using p-values. Reporting findings in descriptive termsdiminishes the ability to replicate findings, being subject to different interpretations. The remainingexcluded abstracts were randomized. Abstracts 5 and 7, however, provided descriptive findings, and then,in minimal detail. Abstract 4 compared NaOCL to CHX. Yet, the outcome measured inflammatorychanges rather than bacterial counts.Determining the best-case seriesAs a result of the analysis, 2 out of the 8 abstracts were included in the best case series, 25% of the totalabstracts in the initial case series. The best case series included Abstracts 2 and 6 (Table 5). Bothabstracts had clearly stated objectives that supported the hypotheses provided. Sample size and statisticalanalyses were appropriate to reporting the study findings. Significant results were reported that weresufficiently detailed and included p-values. Finally, findings from Abstracts 2 and 6 could be applied toanswering the research question (Table 6)Table 6. Quality Assessment Scores Attributes: Table provides full explanations of the two scores andlists the qualities each possesses. Also included is the analysis of the missing desirable qualities fromboth research designs.
None of the excluded and included abstracts met all assessment criteria. While human teeth were used,the studies comprised in vitro conditions in that they were laboratory, not human studies. None usedblinding. With these deficiencies, the validity of the evidence is decreased.DiscussionThe Acceptance score for the best case series is 57%. The acceptance score provides an evaluation ofexisting research relevant to the research question. By setting the level at 65%, acceptable research studydesigns are separated from unacceptable designs. At this time, the highest level of evidence is arandomized in vitro study.The quality of the evidence for the best case series did not meet all the criteria in providing completeevidence to answer the research question. The reliability of the evidence was supported by randomization.The evidence, however, lacked sufficient validity. The major decrement in validity was the lack of in vivoconditions, using teeth in human subjects. Instead, the studies were carried out under in vitro, orlaboratory, conditions. While the NaOCL test group acted as the control group, investigator blinding wasnot done, further decreasing validity. With Summary scores ranging from 60% to 65%, the abstracts ofthe best case series did not meet many of the criteria, for example, confidence intervals, powercalculations, and using human subjects.On a scale from poor (69% and below) to excellent (90% and above), the best case series suggests that thebest available evidence is poor. While poor, the evidence is the best available evidence at this time inanswering the research question for the subsequent systematic review.ConclusionThe randomized, in vitro study design renders the best evidence in answering the research question. TheAcceptance score for available best evidence at this time is 57%. This score suggests that the availableevidence is poor. Therefore, the evidence may not be sufficient in conducting a systematic review whoseresults will have relevance in current clinical practice. More research is needed to update and improve theAcceptance score to reflect new evidence in answering like research questions: “Will 5.25% sodiumhypochlorite compared to 2% chlorhexidine gluconate reduce E. faecalis counts in the root canal space?”Future research requires the use of in vivo study designs.References 1. Ferguson, D.B., Marley, J.T., Hartwell, G.R., (2003). The effect of chlorhexidine gluconate as an endodontic irrigant on the apical seal: long-term results. Journal of Endodontics. 29(2), 91-94. 2. Jeansonne M. J., White R. R., (1994). A Comparison of 2.0% Chlorhexidine Gluconate and 5.25% Sodium Hypochlorite as Antimicrobial Endodontic Irrigants / Journal of Endodontics. 20(6), 276- 278. 3. Niu, W., Yoshioka, T., Kobayashi, C., Suda, H., (2002). A scanning electron microscopic study of dentinal erosion by final irrigation with EDTA and NaOCl solutions. International Endodontic Journal. 35(11), 934-939. 4. Oncag, O., Hosgor M., Hilmioglu., S, Zekioglu., O., Eronat C., (2003). Comparison of antibacterial and toxic effects of various root canal irrigants. Interational Endodondic Journal. 36(6), 423-432. 5. Shabahang, S.,Torabinejad M., (2003) Effect of MTAD on Enterococcus faecalis-contaminated root canals of extracted human teeth. Journal of Endodontics. 29(9), 576-579. 6. Sirtes G, Waltimo T, Schaetzle M, Zehnder M., (2005) The effects of temperature on sodium hypochlorite short-term stability, pulp dissolution capacity, and antimicrobial efficacy. Journal of Endodontics, 31(9), 669-71. 7. Tanomaru, F. M., Leonardo, M.R., Silva, L.A., Anibal, F.F., Faccioli, L.H., (2002) Inflammatory response to different endodontic irrigating solutions. International Endodontic Journal, 35(9), 735- 739.
8. Timmer, A., Sutherland, L.R., Hilsden, R.J. (2003). Development and evaluation of a quality score for abstracts. BMC Med Res Methodol.9. Weber, C. D., McClanahan, S.B., Miller, G. A., Diener-West, M., Johnson, J. D., (2003). The Effect of Passive Ultrasonic Activation of 2% Chlorhexidine or 5.25% Sodium Hypochlorite Irrigant on Residual Antimicrobial Activity in Root Canals. Journal of Endodontics. 29(9), 562- 564.10. Yamashita, J.C., Tanomaru F.M., Leonardo, M.R., Rossi, M.A., (2003). Scanning electron microscopic study of the cleaning ability of chlorhexidine as a root-canal irrigant. International Endodontic Journal. 36(6), 391-394.