Disinfection of the root canal system and its general effect on endodontic outcomes is a complex issue, parts of which have been studied widely, but its specific effect is not well documented in clinical trials with high levels of clinical evidence. Many steps are performed during endodontic therapy and they involve methods that try to disinfect the root canal system. Many of these methods have been investigated, particularly in in-vitro testing, but clinical outcome studies are difficult because of the many steps involved. It is difficult to examine which specific steps may improve outcomes. These steps include irrigation, instrumentation, and intracanal medication. Other factors are different irrigating solutions and different concentrations of irrigants; size and length of instrumentation; method of delivery of irrigants; one visit versus two visits; and initial therapy versus retreatment.
Difficulty in assessing clinical outcomes is because of the lack of randomized clinical trials where one specific step is evaluated in terms of outcome and other steps used to disinfect are the same; so there is only one variable. The levels of clinical evidence are listed in Tables 5.1 and 5.2. These high-level studies of clinical outcomes are difficult to perform for a number of reasons, ranging from adequate sample size, different criteria for healing, lack of standardization, differences in study designs, time of recall, adequate number or recalls, and ethical concerns, to name a few. The clinician is left to formulate evidence for treatment techniques that are based on a combination of studies of lower clinical evidence to predict the outcome of treatment for patients. This chapter addresses some of the information that exists for the disinfection of root canal systems, using what evidence is known in the literature to predict outcomes.
Table 5.1 Levels of clinical evidence.
|Levels of evidence||Therapy/prevention, etiology/harm|
|1a||Systematic review of randomized controlled trial (RCT)|
|1b||RCT (with narrow confidence interval)|
|1c||All or none|
|2a||Systematic review of cohort studies|
|2b||Individual cohort study (including low-quality RCT; i.e., <80%)|
|3a||Systematic review of case-controlled studies|
|3b||Individual case-controlled study|
|4||Case series (and poor-quality cohort and case-control studies)|
|5||Expert opinion without explicit critical appraisal, or based on physiology, bench research, or “proof of principle study”|
|Bench top studies|
Journal of Evidence Based Dental Practice. Reproduced with permission of Elsevier.
|Level||Therapy/prevention, etiology/harm||Prognosis||Diagnosis||Differential diagnosis/symptom prevalence study||Economic and decision analyses|
|1a||SR (with homogeneity*) of RCTs||SR (with homogeneity*) of inception cohort studies; CDR† validated in different populations||SR (with homogeneity*) of level 1 diagnostic studies; CDR† with 1b studies from different clinical centers||SR (with homogeneity*) of prospective cohort studies||SR (with homogeneity*) of level 1 economic studies|
|1b||Individual RCT (with narrow confidence interval‡)||Individual inception cohort study with >80% follow-up; CDR† validated in a single population||Validating** cohort study with good††† reference standards; or CDR† tested within one clinical center||Prospective cohort study with good follow-up****||Analysis based on clinically sensible costs or alternatives; systematic review(s) of the evidence; and including multiway sensitivity analyses|
|1c||All or none§||All or none case series||Absolute SpPins and SnNouts††||All or none case series||Absolute better-value or worse-value analyses††††|
|2a||SR (with homogeneity*) of cohort studies||SR (with homogeneity*) of either retrospective cohort studies or untreated control groups in RCTs||SR (with homogeneity*) of level >2 diagnostic studies||SR (with homogeneity*) of 2b and better studies||SR (with homogeneity*) of level >2 economic studies|
|2b||Individual cohort study (including low quality RCT; e.g., <80% follow-up)||Retrospective cohort study or follow-up of untreated control patients in an RCT; Derivation of CDR† or validated on split-sample§§§ only||Exploratory** cohort study with good††† reference standards; CDR† after derivation, or validated only on split-sample§§§ or databases||Retrospective cohort study, or poor follow-up||Analysis based on clinically sensible costs or alternatives; limited review(s) of the evidence, or single studies; and including multiway sensitivity analyses|
|2c||“Outcomes” research; ecological studies||“Outcomes” research||Ecological studies||Audit or outcomes research|
|3a||SR (with homogeneity*) of case-control studies||SR (with homogeneity*) of 3b and better studies||SR (with homogeneity*) of 3b and better studies||SR (with homogeneity*) of 3b and better studies|
|3b||Individual case-control study||Nonconsecutive study; or without consistently applied reference standards||Nonconsecutive cohort study; or very limited population||Analysis based on limited alternatives or costs, poor quality estimates of data, but including sensitivity analyses incorporating clinically sensible variations|
|4||Case series (and poor quality cohort and case-control studies§§)||Case series (and poor quality prognostic cohort studies***)||Case-control study, poor or nonindependent reference standard||Case series or superseded reference standards||Analysis with no sensitivity analysis|
|Level||Therapy/prevention, etiology/harm||Prognosis||Diagnosis||Differential diagnosis/symptom prevalence study||Economic and decision analyses|
|5||Expert opinion without explicit critical appraisal, or based on physiology, bench research, or “first principles”||Expert opinion without explicit critical appraisal, or based on physiology, bench research, or “first principles”||Expert opinion without explicit critical appraisal, or based on physiology, bench research, or “first principles”||Expert opinion without explicit critical appraisal, or based on economic theory or “first principles”|
Oxford Center for Evidenced-based Medicine—Levels of Evidence (March 2009) www.cebm.net/index.aspx?o=1025.
Produced by Bob Phillips, Chris Ball, Dave Sackett, Doug Badenoch, Sharon Straus, Brian Haynes, Martin Dawes since November 1998. Updated by Jeremy Howick March 2009.
Users can add a minus sign “−” to denote the level that fails to provide a conclusive answer because of either a single result with a wide confidence interval or a systematic review with troublesome heterogeneity.
Such evidence is inconclusive, and therefore can only generate Grade D recommendations.
* By homogeneity we mean a systematic review that is free of worrisome variations (heterogeneity) in the directions and degrees of results between individual studies. Not all systematic reviews with statistically significant heterogeneity need be worrisome, and not all worrisome heterogeneity need be statistically significant. As noted above, studies displaying worrisome heterogeneity should be tagged with a “−” at the end of their designated level.
† Clinical Decision Rule. (These are algorithms or scoring systems that lead to a prognostic estimation or a diagnostic category.)
‡ See note above for advice on how to understand, rate, and use trials or other studies with wide confidence intervals.
§ Met when all patients died before the Rx became available, but now some survive on it; or when some patients died before the Rx became available, but now none die on it.
§§ By poor quality cohort study we mean one that failed to clearly define comparison groups and/or failed to measure exposures and outcomes in the same (preferably blinded), objective way in both exposed and nonexposed individuals and/or failed to identify or appropriately control known confounders and/or failed to carry out a sufficiently long and complete follow-up of patients. By poor quality case-control study we mean one that failed to clearly define comparison groups and/or failed to measure exposures and outcomes in the same (preferably blinded), objective way in both cases and controls and/or failed to identify or appropriately control known confounders.
§§§ Split-sample validation is achieved by collecting all the information in a single tranche, then artificially dividing this into “derivation” and “validation” samples.
†† An “Absolute SpPin” is a diagnostic finding whose specificity is so high that a positive result rules-in the diagnosis. An “Absolute SnNout” is a diagnostic finding whose sensitivity is so high that a negative result rules out the diagnosis.
‡ Good, better, bad, and worse refer to the comparisons between treatments in terms of their clinical risks and benefits.
††† Good reference standards are independent of the test, and applied blindly or objectively to all patients. Poor reference standards are haphazardly applied, but still independent of the test. Use of a nonindependent reference standard (where the “test” is included in the “reference,” or where the “testing” affects the “reference”) implies a level 4 study.
†††† Better-value treatments are clearly as good but cheaper, or better at the same or reduced cost. Worse-value treatments are as good and more expensive, or worse and equal or more expensive.
** Validating studies test the quality of a specific diagnostic test, based on prior evidence. An exploratory study collects information and trawls the data (e.g., using a regression analysis) to find which factors are “significant.”
*** By poor quality prognostic cohort study, we mean one in which sampling was biased in favor of patients who already had the target outcome, or the measurement of outcomes was accomplished in less than 80% of study patients, or outcomes were determined in an unblinded, nonobjective way, or there was no correction for confounding factors.
**** Good follow-up in a differential diagnosis study is greater than 80%, with adequate time for alternative diagnoses to emerge (e.g., 1–6 months acute, 1–5 years chronic).
Grades of recommendation
|A||Consistent level 1 studies|
|B||Consistent level 2 or 3 studies or extrapolations from level 1 studies|
|C||Level 4 studies or extrapolations from level 2 or 3 studies|
|D||Level 5 evidence or troublingly inconsistent or inconclusive studies of any level|
“Extrapolations” are where data is used in a situation that has potentially clinically important differences than the original study situation.
It is understood that if a canal system can be filled after a negative culture is obtained, the outcome is better (1). Which steps produce a canal system with a low level of bacteria remaining are of some dispute, and what level is critical to produce a significantly higher outcome is not known.
What is needed is a series of randomized clinical trials, systematic reviews, and meta-analysis of these systematic reviews.
Nair (2) lists the following causes for persistent apical periodontitis: intraradicular infection (intraradicular bacteria); extraradicular infection found in apical tissues (Actinomyces, Enterococcus, and Propionibacterium, among others); cystic apical periodontitis (radicular cysts that do not heal after nonsurgical endodontic treatment, and may require surgical endodontic treatment, also known as true cysts); the presence of cholesterol crystals that may give rise to a foreign body reaction; the presence of foreign bodies in apical tissues that may include gutta-percha, root canal sealers, plant materials, paper points, cotton fibers, amalgam, or other materials; and, finally, the persistent apical lesion may actually heal by scar tissue formation. The presence of intracanal microorganisms is by far the most common cause of persistent apical periodontitis and is most relative to outcomes affected by the disinfection of canals.
Friedman (3) has compared outcome studies and the effects of numerous factors on the outcome of endodontic treatment in terms of healed apical periodontitis, healing of apical periodontitis, and asymptomatic functional teeth.
Friedman reviewed preoperative factors such as the patient’s age and gender, the patient’s systemic health, tooth location, the presentation of clinical signs and symptoms, the status of the pulp, the presence or absence of apical periodontitis, the size of the radiolucent lesion, and the status of the periodontium, and in the case of endodontic retreatment, the time elapsed from initial treatment to retreatment, the existence of a previous perforation, and the quality of the previous root canal filling.
The intraoperative factors that Friedman (3) examined in outcome studies include the apical extent of treatment, the amount of apical enlargement, negative bacterial cultures before root canal filling, number of treatment sessions (one visit vs. two visits), the occurrence of midtreatment flare-ups, materials and techniques used for treatment, and midtreatment complications.
Friedman also examined postoperative factors, such as the type and presence of an adequate restoration after endodontic treatment.
The findings in most outcome studies examined by Freidman (3) are that the presence of apical periodontitis seems to influence the prognosis to the greatest degree, and that other factors are less defined in terms of outcomes. Apical periodontitis is caused by root canal infection, and the presence of microorganisms within the canal can continue and expand apical periodontitis. In addition, apical periodontitis can be developed if bacteria are reintroduced into the root canal system after initially eliminating them.
Kakehashi et al. (4) demonstrated the direct correlation between the presence of bacteria and pulpal and apical infection and disease. Sjogren et al. (1) showed that the bacteriological status of the root canal at the time of root canal obturation may be a critical factor in determining the outcome of endodontic treatment. Other studies have shown the importance of bacteria on the development of apical periodontitis (5, 6).
Bacteria elimination from root canals, specifically, the effect of irrigation, intracanal interappointment medication, and the effect of apical enlargement during root canal preparation have been investigated. In the subsequent sections, the elimination of bacteria from root canal systems by means of chemicals is discussed, along with the effect of this elimination of bacteria on the outcome of nonsurgical endodontic treatment. Using real-time polymerase chain reaction, it was found that root canals with primary infections contain higher bacterial loads and that chemomechanical root canal preparations can reduce bacterial counts by at least 95% (7).
Irrigation is one of the most important steps in endodontic therapy. It carries out many functions including tissue dissolution, lavage, killing of microorganisms, removal of debris, lubrication of the canal for instrumentation, and smear layer removal (8). Disruption of biofilms is an important factor in reducing endodontic infections (9–11).
The best solution to be used for irrigation has been extensively studied, but, in terms of strong clinical evidence, there is no conclusive evidence. Several solutions have been used ranging from water, saline, sodium hypochlorite (NaOCl), chlorhexidine (CHX), iodine potassium iodide, ethylenediaminetetraacetic acid (EDTA), hydrogen peroxide (H2O2), urea peroxide, citric acid, dequalinium acetate, and others (8). The most widely used irrigating solutions are sodium hypochlorite, chlorhexidine, and iodine potassium iodide; and the solution most widely used as a chelating agent for irrigation and for the removal of the inorganic portion of the smear layer is EDTA.
NaOCl has a broad antimicrobial spectrum. It dissolves both necrotic and vital pulp tissue. It inactivates endotoxin and dissolves the organic portion of the smear layer (5).
The germicidal ability of NaOCl comes from the formation of hypochlorous acid when it contacts organic debris. Hypochlorous acid oxidizes the sulfhydryl groups of bacterial enzymes, disrupting metabolism(12). Hand et al. (13) found that 5.25% NaOCl was significantly more effective as a necrotic tissue solvent than 2.5% NaOCl, 1.0% NaOCl, 0.05% NaOCl, distilled water, normal saline solution, or 3% H2O2. Rosenfeld et al. (14) discovered that 5.25% NaOCl can dissolve vital pulp tissue, but the ability of NaOCl to dissolve tissues is limited in confined spaces, such as a root canal. Stojicic et al. (15) found that optimizing the concentration, temperature, flow, and surface tension can improve the tissue-dissolving effectiveness of NaOCl.
Chlorhexidine (CHX) is a cationic bisbiguanide. Chlorhexidine’s antibacterial action is possible following the absorption onto the bacterial surface and disruption of the cytoplasmic membrane (16). CHX solutions have been used as an irrigant, but are unable to dissolve necrotic tissue, and are less effective against gram-negative bacteria than gram-positive bacteria (5). CHX has good substantivity in root canals when used as an irrigant or medicament (17–20). CHX has good antimicrobial action both when used as an irrigant and as a medicament used in conjunction with calcium hydroxide (12, 21–24).
There is some controversy over whether para-chloroaniline is formed when CHX is used in combination with NaOCl (25–30).
Iodine potassium iodide
The molecular iodine (I2) is the active portion of the solution. The iodine has a similar action as chlorine in sodium hypochlorite (31, 32). The iodine does not dissolve necrotic tissue (33); however, it is bactericidal, fungicidal, virucidal, and sporicidal, but to a lesser degree than sodium hypochlorite (34, 35). It is less cytotoxic than sodium hypochlorite (34, 36). Iodine potassium iodide does have a high allergic potential and may also stain dentin.
Clinical evidence to assess the effects of irrigants used in the nonsurgical root canal treatment of teeth
Although there are many studies on irrigants used in endodontics, documentation of the effect of the irrigants on clinical outcomes is lacking.
Fedorowicz et al. (37) performed a systematic review in the Cochrane review and performed a meta-analysis. They found that NaOCl and chlorhexidine are the commonly used irrigating solutions, but there is uncertainty as to which solution is the most effective.
Ng et al. (38) in a prospective study found that the addition of a rinse with 0.2% chlorhexidine with NaOCl irrigation did not improve the odds of success, but actually decreased the odds of success by 53%.
EDTA and other chelators
EDTA is a chelating agent that removes the inorganic portion of the smear layer, softens dentin, and facilitates the removal of calcific obstructions (39–42). The effects of EDTA on dentin may be self-limiting (43), but prolonged contact of EDTA with dentin for 10 min may cause the erosion of dentin (44). Although EDTA may have some antimicrobial activity, the ability of EDTA to remove smear layer and expose bacteria in dentinal tubules to other more potent antimicrobial agents may be its best quality (45–51).
Ng et al. (38), in a prospective study of the factors affecting the outcomes of nonsurgical root canal treatment, found that the use of an EDTA rinse followed with a final rinse of NaOCl had no significant improvement in the outcome of primary endodontic treatment, but it significantly increased the odds of healing by twofold for cases of secondary endodontic treatment.
Effects of various concentrations of solutions
The ultimate concentrations of these various irrigating solutions have also been investigated with regard to their ability to dissolve vital and necrotic tissue, kill microorganisms, remove debris, remove the smear layer, and their biocompatibility with host tissues.
One study compared three strengths of sodium hypochlorite, 1%, 2.5%, and 5% (52). The higher concentration reduced the number of canals with positive cultures. After final irrigation, 10 of 39 (25.8%) samples irrigated with 1% sodium hypochlorite still had positive cultures; 5 of 36 (13.7%) of samples irrigated with 2.5% sodium hypochlorite still had positive cultures; and only 2 out of 36 (6.6%) of samples irrigated with 5% sodium hypochlorite had positive cultures.
The volume of irrigating solution is thought by some to be a very important factor in the successful outcome of endodontically treated teeth, regardless of the solution or concentration. Baker et al. (53) found that the volume of irrigant used was more important than the solution and recommended using the most biologically acceptable irrigating solution. They found that there was no difference in the effectiveness of any solution tested in removing root canal debris. They examined different volumes of the following solutions: saline, 3% H2O2, 1% NaOCl, 15% EDTA, glyoxide, and RC-Prep (Premier Dental Products, Morristown, PA). It should be noted that the concentration of 1% NaOCl used was less compared to what many clinicians use in the clinical practice of endodontics. There is, however, general agreement that copious volumes of irrigation during treatment are important for many reasons, especially for the lavage of the area.
Fedorowicz et al. (37) in their systematic review could not find clinical evidence as to which concentration or combination of irrigating solutions would lead to a better clinical outcome.
Effect and efficacy of the delivery of irrigating solutions
Another factor to be considered is how the irrigating solution is delivered to the canal. This would include the depth of the irrigating needle penetration into the canal, size and design of the needle used for irrigation, sonic or ultrasonic agitation of the irrigating solution to produce acoustic streaming, and the use of positive or negative pressure irrigation. Related to the depth of irrigation is the size of canal preparation.
If the irrigating needle can reach the apical few millimeters of the canal, irrigation is more effective in debris removal (54, 55). The ability of the irrigating needle to reach the apical portion of the canal is dependent on the size of the preparation of the canal (55–58). Syringe irrigation has been found to be effective in canals with apical preparations 0.3 mm or greater, and ultrasonic irrigation with NaOCl was more effective than syringe irrigation (59). The 27-gauge notch-tip needle has been found to be effective in canals instrumented to size 30 and 35 (60). A brush-covered irrigating needle produced cleaner coronal thirds than conventional irrigation, as found in one study (61).
Sonic and ultrasonic irrigation, especially passive ultrasonic irrigation, has been found to help eliminate debris and bacteria from instrumented root canals, and is effective in the removal of tissue and debris from isthmus areas (62–67). One clinical study looked at the influence of passive sonic irrigation on the elimination of bacteria from root canal systems and found that there was no significant difference between sonic irrigation and standard syringe irrigation in eliminating bacteria from root canals, but multivisit treatment using calcium hydroxide as an intervisit medication did eliminate cultivable bacteria from canals more than the single visit group (68). One study compared passive ultrasonic irrigation to traditional irrigation, passive sonic irrigation, and apical negative pressure irrigation, and found that passive ultrasonic irrigation moved more irrigant into lateral canals than did the other methods of irrigation, but the apical negative pressure irrigation brought more irrigant into the apical extent of the canal (69).
Perazzi et al. (70) in a systematic review of the literature illustrates a “current lack of published or ongoing randomized controlled trials and the unavailability of high-level evidence, based on clinically relevant outcomes, for the effectiveness of ultrasonic instrumentation used alone or as an adjunct to hand instrumentation for orthograde root canal treatment.”
The effectiveness of negative pressure irrigation has been studied and compared to other methods of irrigation. Many investigations have found negative pressure irrigation to be superior in terms of both debris removal and elimination of bacteria, particularly in the apical aspect of the canal (71–75). Cohenca et al. (76), in a randomized controlled clinical trial, found that taper and apical size failed to demonstrate a difference in microbiological reduction of cultivable bacteria, but did find that apical negative pressure irrigation showed a significant difference in the reduction of cultivable bacteria over traditional positive pressure irrigation. Others, who have examined debris removal and the removal of bacteria, have found no differences between negative pressure irrigation and other forms of irrigation (77, 78). One study found that the apical negative pressure irrigation allowed irrigant to reach the apical portions of the canal better than other irrigation regimens (69).
It is recognized that negative pressure irrigation is safer than other forms of irrigation with respect to decreasing or eliminating the possibility of apical extrusion of irrigants (79–81).
As the depth of irrigating needle penetration with traditional irrigation depends on the size of the canal preparation, so does irrigation with negative pressure irrigation (82). Preparation size should be at least to an ISO size 40 with a taper of 0.04 (83). Another study found that with negative pressure irrigation, an apical preparation size of 40 with a 0.06 taper sign/>