WG1: The diagnosis of pulpitis

Outcomes (all written as in protocol): Main outcome(s): A combination of outcome measures will be investigated for diagnostic accuracy with data used to calculate the pooled sensitivity, specificity, diagnostic odds ratio, positive predictive value (PPV) and negative predictive value (NPV) as probabilities for a correct test result and perhaps a receiver operating characteristic (ROC) analysis. For comparative studies and diagnostic nonrandomized and randomized clinical trials designed to combine diagnostic tests and therapeutic interventions, the outcomes of treatment will be primary measures. Additional outcome(s): (a) Pulp survival when teeth with caries are treated with any type of vital pulp treatment. (b) Relieve of pain after an operative procedure.

Time: For the review questions focusing on diagnostic accuracy, there is no time limitation. All other included comparative clinical trials must have a minimum of 1-year follow-up and a maximum of as long as possible.

Study type: Diagnostic accuracy studies examining the accuracy of the method in detecting pulp vitality, level of pulpal inflammation and pulpal condition with respect to whether it is possible to maintain pulpal vitality and cause of tooth pain in permanent teeth in humans. The study must have a gold standard reference, for example, histologic examination or pulpal examination (in vivo). Articles in which the primary objective was to evaluate the accuracy (sensitivity and specificity) of any type of diagnostic tool, radiological technique included, in humans will be selected. Diagnostic studies based on the ability to determine change in outcome or diagnostic decision-making are not the primary outcome but may be included (however, sensitivity/specificity will still be calculated wherever possible).

WG2: The diagnosis of apical periodontitis

Outcomes (as written in protocol): Main outcome(s): A combination of outcome measures will be investigated for diagnostic accuracy with data used to calculate the pooled sensitivity, specificity, diagnostic odds ratio, positive predictive value (PPV) and negative predictive value (NPV) as probabilities for a correct test result and perhaps a receiver operating characteristic (ROC) analysis. Additional outcome(s): For comparative studies and diagnostic nonrandomized and randomized clinical trials designed to combine diagnostic tests and therapeutic interventions, the outcomes of treatment will be primary measures and similar to those described for effectiveness of treatment.

Time: There is no defined duration for diagnostic accuracy and diagnostic thinking studies; however, comparative clinical trials will need to be followed up with a minimum time of 1 year and a maximum of as long as possible.

Study type: Diagnostic accuracy studies examining the accuracy of the method in detecting pulpitis/apical periodontitis (AP) on permanent teeth in humans. The study must have a gold standard reference, such as histologic examination for actual AP or pulpitis, pulpal examination (in vivo) or in situ visualization of bone defects (in vitro). Articles in which the primary objective was to evaluate the accuracy (sensitivity and specificity) of any type of diagnostic tool or radiographic technique in humans will be selected. Diagnostic studies may also be based on the ability to determine change in outcome, diagnostic decision-making or thinking and accuracy may not be the primary outcome (however, sensitivity/specificity can still be calculated). This will require other types of prospective comparative study design including before and after studies and trials.

WG1: The treatment of pulpitis

Outcomes: Main outcome(s): A combination of patient and clinician-reported outcome measures. The most critical outcome is ‘tooth survival’. Other critical outcomes are ‘pain, tenderness, swelling, need for medication (analgesics)’, ‘evidence of emerging apical radiolucency’ and ‘response to pulp sensibility test (not for full pulpotomy or pulpectomy)’. Additional outcome(s): Important outcomes are as follows: ‘tooth function (fracture, restoration longevity)’, ‘need for further intervention’, ‘adverse effects (including exacerbation, restoration integrity, allergy)’, ‘oral health-related quality of life (OHRQoL)’, ‘presence of sinus tract’ and ‘radiological evidence of continued root formation’.

Time: Defined a minimum of 1 year and maximum of as long as possible for all outcome measures, except ‘pain, tenderness, swelling, need for medication (analgesics)’, which is a minimum of 7 days and a maximum of 3 months, and OHRQoL, which is minimum of 6 months and a maximum of as long as possible.

Study type: Human clinical trials studies (randomized control trials, comparative clinical trials [CCTs]—nonrandomized, longitudinal observational studies [retrospective and prospective comparative cohort and case–control studies]). The number of patients needs to be at least 20 (10 in each arm) at the end of the study.

WG2: The treatment of apical periodontitis

Outcomes: Main outcome(s): A combination of patient- and clinician-reported outcome measures. The most critical outcome is ‘tooth survival’. Other critical outcomes are ‘pain, tenderness, swelling, need for medication (analgesics, antibiotics)’, ‘radiographic evidence of reduction of apical lesion size (loose criteria)’ and ‘radiographic evidence of normal periodontal ligament space (strict criteria)’. Additional outcome(s): Important outcomes are as follows: ‘tooth function (fracture, restoration longevity)’, ‘need for further intervention’, ‘adverse effects (including exacerbation, restoration integrity, allergy)’, ‘OHRQoL’ and ‘presence of sinus tract’.

Time: Defined a minimum of 1 year and a maximum of as long as possible for all outcome measures, except ‘pain, tenderness, swelling, need for medication (analgesics)’, which is a minimum of 7 days and a maximum of 3 months, and OHRQoL, which is minimum of 6 months and maximum of as long as possible.

Study type: Human clinical trials studies (randomized control trials, comparative clinical trials [CCTs]—nonrandomized, longitudinal observational studies [retrospective and prospective comparative cohort and case–control studies]). The number of patients needs to be at least 20 (10 in each arm) at the end of the study.

WG3: The surgical treatment of apical periodontitis

Outcomes: Main outcome(s): Most critical outcome ‘tooth survival’. Other critical outcomes: ‘pain, tenderness, swelling, need for medication (analgesics, antibiotics)’, ‘presence of sinus tract, satisfactory soft tissue healing’, ‘radiographic evidence of reduction of apical lesion size (loose criteria)’ and ‘radiographic evidence of normal periodontal ligament space (strict criteria)’. Additional outcome(s): Important outcomes are as follows: ‘need for further intervention’, ‘adverse effects (including exacerbation, restoration integrity, allergy)’, ‘OHRQoL’ and ‘mobility’.

Time: Defined a minimum of 1 year and a maximum of as long as possible for all outcome measures, except ‘pain, tenderness, swelling, need for medication (analgesics)’, which is a minimum of 7 days and a maximum of 3 months, and OHRQoL, which is minimum of 6 months and maximum of as long as possible.

Study type: Human clinical trials studies (randomized control trials, comparative clinical trials [CCTs]—nonrandomized, longitudinal observational studies [retrospective and prospective comparative cohort and case–control studies]). The number of patients need to be at least 20 (10 in each arm) at the end of the study.

WG4: The regenerative treatment of apical periodontitis

Outcomes: Main outcome(s): The most critical outcome is ‘tooth survival’, Other critical outcomes are ‘pain, tenderness, swelling, need for medication (analgesics, antibiotics)’, ‘radiographic evidence of reduction of apical lesion size (loose criteria)’, ‘radiographic evidence of normal periodontal ligament space (strict criteria)’ and ‘radiographic evidence of increased root thickness and length’. Additional outcome(s): Important outcomes are as follows: ‘tooth function (fracture, restoration longevity)’, ‘need for further intervention’, ‘adverse effects (including exacerbation, restoration integrity, allergy, discolouration)’, ‘OHRQoL’, ‘presence of sinus tract’ and ‘response to sensibility testing’.

Time: Defined as a minimum of 1 year and a maximum of as long as possible for all outcome measures, except ‘pain, tenderness, swelling, need for medication (analgesics)’, which is a minimum of 7 days and a maximum of 3 months, and OHRQoL, which is a minimum of 6 months and a maximum of as long as possible.

Study type: Human experimental studies (randomized control trials, comparative clinical trials [CCTs]– nonrandomized). Our search will be supplemented by longitudinal observational studies (retrospective and prospective comparative cohort and case–control studies) to ensure that all relevant clinical information that is often not tested in experimental studies is captured.

The number of patients is to be at least 20 (10 in each arm) at the end of the study.

Intervention

With respect to the assessment of diagnostic accuracy of pulp vitality assessment, cold and heat testing, electric pulp tester (EPT), pulse oximeter and percussion tests were investigated. The reference standards used were histology of pulp after tooth extraction (Dummer et al., 1980; Seltzer et al., 1963) or direct visual inspection of pulp tissue (Dastmalchi et al., 2012; Farid et al., 2015; Gopikrishna et al., 2007; Hazard et al., 2021; Jespersen et al., 2014; Kamburoglu & Paksoy, 2005; Petersson et al., 1999; Pigg et al., 2016; Villa-Chávez et al., 2013; Weisleder et al., 2009). With regards to diagnostic accuracy of the pulpal condition, thermal tests, presence and history of pain, spontaneous pain, pain at night (nocturnal), sensibility to percussion, pulp exposure by caries and expression of biomarkers were used as criteria. For assessment of biomarker expression, only studies that confirmed pulpal inflammation using classical histopathological criteria were included. For assessment of pulp condition, histology of the pulp tissue after extraction was used as the reference standard.

Available evidence

Twenty-eight diagnostic accuracy studies, 12 focusing on pulp vitality assessment (Dastmalchi et al., 2012; Dummer et al., 1980; Farid et al., 2015; Gopikrishna et al., 2007; Hazard et al., 2021; Jespersen et al., 2014; Kamburoglu & Paksoy, 2005; Petersson et al., 1999; Pigg et al., 2016; Seltzer et al., 1963; Villa-Chávez et al., 2013; Weisleder et al., 2009), 10 on diagnosis of the pulp condition (Barańska-Gachowska et al., 1969; Barańska-Gachowska & Waszkiewicz-Gołoś, 1969; Cisneros-Cabello & Segura-Egea, 2005; Dummer et al., 1980; Garfunkel et al., 1973; Hasler & Mitchell, 1970; Johnson et al., 1970; Ricucci et al., 2014; Seltzer et al., 1963; Tyldesley & Mumford, 1970) and 6 on expression of biomarkers (Abd-Elmeguid et al., 2013; Di Nardo Di Maio et al., 2004; Giuroiu et al., 2017; Petrini et al., 2012; Rauschenberger et al., 1997; Silva et al., 2009) were included in the review (Donnermeyer et al., 2022). Due to the considerable heterogeneity between the included studies and the fact that only one study provided 95% confidence intervals for all measures of validity (Pigg et al., 2016), and furthermore, due to the prevalence values of disease being highly heterogeneous, pooling predictive values from different studies was not possible. Therefore, calculation of effect sizes and confidence intervals was regarded as inappropriate.

None of the studies looked specifically at teeth without spontaneous pain. The studies examined the accuracy of the diagnostic methods including clinical findings such as symptoms, depth of caries lesion, pulp exposure, bleeding or presence of biomarkers in detecting the level of pulpal inflammation and pulpal condition with respect to if it is possible to maintain pulpal health in teeth with suspected pulpitis and no spontaneous pain. The comparator was a gold standard reference, such as (i) pulp survival, when teeth with suspicion of pulpitis were treated with any type of vital pulp treatment (Careddu & Duncan, 2021; Marques et al., 2015; Matsuo et al., 1996), (ii) histological evaluation of the pulp tissue after extraction and (iii) quantification of inflammatory mediators.

Risk of bias

All included studies regarding diagnostic accuracy of pulp vitality and accuracy of the pulp condition were considered to have a certain degree of bias. According to the QUADAS-2 tool for diagnostic accuracy studies and the Newcastle–Ottawa scale, the study quality was considered to be moderate for seven studies (Cisneros-Cabello & Segura-Egea, 2005; Gopikrishna et al., 2007; Hasler & Mitchell, 1970; Hazard et al., 2021; Pigg et al., 2016; Ricucci et al., 2014; Villa-Chávez et al., 2013) and unsatisfactory for all other studies included. For expression of biomarkers, most studies were considered as satisfactory according to the risk of bias assessment, whilst one study was rated as good (Abd-Elmeguid et al., 2013).

Consistency

Considerable heterogeneity between the included studies was obvious with regard to aspects related to patients (age, gender distribution and history of previous pain), assessors (blinded, two or more independent assessors and level of experience), type and clinical conditions of included teeth (caries, intrapulpal mineralization, condition of the pulp tissue, type and quality of coronal restorations) and prevalence of disease.

Clinical relevance and effect size

Effect sizes were not reported in any of the included studies. The diagnostic odds ratios (DOR) for cold used to determine pulp vitality were in the range 2.19–664.29. Regarding assessment of pulp conditions, DOR values were in the range 5–88 to 11.01 for ‘presence of pain’, 17.73 for ‘previous pain’, 31.41 for ‘spontaneous pain’, 24.62 for ‘pulp exposure’, 11.6 for ‘pain on heat’ and in the range 2.54–14.27 for ‘tenderness to percussion’.

Balance of benefits and harm

No serious adverse effects were reported, but the benefit of accurate diagnosis for provision of correct treatment and avoidance of overtreatment is obvious.

Ethical considerations

Not applicable.

Legal considerations

Not applicable.

Economic considerations

No cost-effectiveness outcomes were reported. Cost associated with use of combination of diagnostic test can be justified by the need to arrive at accurate diagnosis to facilitate provision of conservative less costly vital pulp treatments.

Patient preferences and values

No patients' preference/acceptability were reported for any of the diagnostic accuracy studies.

Applicability

Most tests are technically easy to use. Most of the studies were carried out in hospital or university settings (Efficacy) but few in general dental practice ‘real-world’ environments (Effectiveness). Although pulse oximetry was found to represent a reliable method to assess pulp vitality with an accuracy of 97.5% (Gopikrishna et al., 2007) and the fact that pulp necrosis was correctly identified in 93% to 100% of the teeth (sensitivity) and vital pulps in 95% to 100% of the teeth (specificity) (Dastmalchi et al., 2012; Gopikrishna et al., 2007), eligible commercially available devices for this specific test are currently not available. Therefore, at the moment, application of pulse oximetry would represent an off-label use and require modification of a probe for dental purposes.

Intervention

Patient symptoms and clinical information alone cannot reliably be used to assess the presence or absence of apical periodontitis, as the disease is chronic in nature, often with minimal pain and discomfort for the patient. It, therefore, becomes important to study to what extent imaging techniques display histopathological changes associated with apical periodontitis in humans. Studies using human cadavers have been used to investigate this since taking adequate biopsies in vivo, including the entire periapical area, would be considered unethical. The present study included only diagnostic accuracy studies including healthy reference teeth as a comparison. The only two radiographic modalities providing such information were studies on periapical radiography and CBCT.

Available evidence

In total, six studies comparing radiographic imaging with the true state of the periapical tissues verified by histology were included (Barthel et al., 2004; Brynolf, 1967; Green et al., 1997; Kanagasingam, Hussaini, et al., 2017; Kanagasingam, Lim, et al., 2017; Kruse et al., 2019). Two of the included studies were performed on the same study sample (Kanagasingam, Hussaini, et al., 2017; Kanagasingam, Lim, et al., 2017).

Periapical radiography: Five studies were identified and included (Barthel et al., 2004; Brynolf, 1967; Green et al., 1997; Kanagasingam, Hussaini, et al., 2017; Kanagasingam, Lim, et al., 2017). Considerable heterogeneity was seen amongst the radiographic protocols, including both conventional and digital radiographs. Furthermore, the exposure settings, object tube distance and beam angulations varied. In two studies, additional radiographs of each study object were taken. In two studies, the study object was teeth; one of these included only single-rooted teeth. In two studies, the study object was root. The two studies performed on the same study sample included only roots that were not root filled. One study included only root filled roots (Barthel et al., 2004), and two studies included both root filled and non-root filled teeth (Brynolf, 1967; Green et al., 1997).

CBCT: Two studies were identified and included. In both studies, the study object was root. Heterogeneity was seen in relation to CBCT unit, radiographic settings and protocols and disease threshold. One study included only non-root filled teeth (Kanagasingam, Lim, et al., 2017), whereas the other study included both root filled and non-root filled roots (Kruse et al., 2019).

Risk of bias

Periapical radiography: Three of the studies were based on teeth, one of these was assessed to have a high risk of bias (n teeth = 39) and one study was assessed to have some concerns regarding risk of bias (n teeth = 217). Two studies were based on roots, and for these studies, some concerns were noted when assessing risk of bias (n roots = 139).

CBCT: Two studies were identified and included (n roots = 421). Both studies were assessed to have some concerns regarding risk of bias.

Consistency

Considerable heterogeneity between the studies was obvious, regarding the study object, radiographic protocol and threshold for disease. However, specificity for both periapical radiographic imaging and CBCT was high. Overall, sensitivity was lower compared with specificity. Sensitivity in relation to periapical radiographic imaging was lower compared with CBCT, except for CBCT on root filled roots. Two studies, based on the same study sample, reported considerably lower sensitivity in relation to periapical radiography compared with the other three studies reporting on that parameter.

Clinical relevance and effect size

Periapical radiography: Specificity, the ability to identify the healthy, was high in all the studies ranging from 0.86 to 1.00. Sensitivity, the ability to identify disease, varied amongst studies from 0.27 to 0.90 (Barthel et al., 2004; Brynolf, 1967; Green et al., 1997; Kanagasingam, Hussaini, et al., 2017; Kanagasingam, Lim, et al., 2017).

CBCT: Specificity, the ability to identify the healthy, ranged from 0.69 to 1.00. Sensitivity, the ability to identify the diseased, ranged from 0.63 to 0.89 (Kanagasingam, Lim, et al., 2017; Kruse et al., 2019).

The studies used different thresholds, and sensitivity and specificity may differ accordingly. A low level of demineralization may create more uncertainty in the diagnostic accuracy.

Balance of benefits and harm

Additional cost and radiation of CBCT may be justified in selected cases. However, in relation to root filled teeth, there may be a significant risk of overdiagnosis, which could result in overtreatment of the patient if not combined with information from the clinical examination and testing.

Ethical considerations

Additional costs and radiation of CBCT data acquisitions should be considered in light of potential benefits in selected cases.

Applicability

Knowledge of the diagnostic accuracy related to radiographic imaging techniques should be applied when diagnosing apical periodontitis in patients. However, radiographic images in accuracy studies on cadavers have been acquired under optimal conditions, with no patient movement and on selected roots/teeth. It should be recognized that these conditions may not directly apply to the clinical situation, and may affect the certainty of a diagnosis.

Intervention

In teeth with caries in proximity to the pulp, different treatment options intended to preserve pulp tissue are available to the clinician. A conservative approach aims to avoid pulp exposure by retaining and sealing residual caries in proximity to the pulp and either restoring with immediate placement of a permanent restoration (selective caries removal) or with the placement of a temporary restoration and subsequent re-entry and permanent restoration (stepwise caries removal). Selective one-stage carious-tissue removal or stepwise excavation was recommended for the management of deep carious lesions to avoid pulp exposure when the tooth is asymptomatic or has signs and symptoms indicative of no worse than reversible pulpitis (ESE, 2019). In RCTs after performing selective/stepwise carious removal, 56 to 80% of teeth responded to sensibility tests and had no signs of emerging apical radiolucency after 1 to 3 years (Bjørndal et al., 2010; Maltz et al., 2012).

In contrast, direct pulp capping or pulpotomy (partial/full) after nonselective caries removal to ‘hard’ dentine aims to treat the inflamed/infected pulp tissue and capping with a suitable bioactive material. After direct pulp capping or pulpotomy (partial/full), 9% to 100% of teeth responded to sensibility tests and/or had no signs of emerging apical periodontitis after 1 to 5 years (Asgary et al., 2018; Bjørndal et al., 2017; Careddu & Duncan, 2021; Kundzina et al., 2017; Marques et al., 2015). Furthermore, an enhanced disinfection protocol has been recommended for these procedures (Ballal et al., 2022; ESE, 2019).

Available evidence

No studies with direct comparison were available.

Risk of bias

No studies were identified.

Consistency

N/A.

Clinical relevance and effect size

Maintaining pulp vitality is important for long-term survival of the tooth (Duncan, 2022). Therefore, treatment methods that create better conditions for the long-term preservation of a vital pulp are important and clinically relevant. This PICO highlights an important area for further research.

Balance of benefits and harm

The increased risk for pulp exposure associated with nonselective caries removal can be considered as a potential harm. However, this does not apply if vital pulp treatment following pulp exposure would achieve comparable or better results in terms of on-term survival of the pulp compared with selective excavation. The choice of treatment is hampered by the lack of objective measures of pulp inflammation and there are no available studies comparing these treatments and/or evaluating potential harms and benefits.

Ethical considerations

A direct comparison between selective caries removal and treatment after pulp exposure is challenging but high priority.

Accessibility, affordability and equity issues

Selective caries removal is a simple and affordable treatment that should be available in every setting. For teeth with pulp exposures due to caries, an enhanced protocol has been recommended regarding pulp capping or pulpotomy (partial/full), adding the use of aseptic conditions, magnification, disinfection of the exposed pulp and the use of suitable bioactive capping material. In general, vital pulp treatment is considered less technically demanding than root canal treatment.

Legal considerations

Not applicable.

Economic considerations

No cost-effectiveness analysis has been made based on a study directly comparing treatments. Vital pulp treatment following pulp exposure is anticipated to be more expensive than vital pulp treatment without pulp exposure but cheaper than root canal treatment.

Patient preferences and values

There is no evidence supporting one approach over the other but a preference for a less invasive and more affordable method would be likely.

Applicability

Data are lacking on treatment of older age groups. Furthermore, studies have mainly been performed in university settings.

Intervention

In teeth with deep caries in proximity to the pulp, the pulp may be exposed after removal of the carious tissue. For direct pulp capping, a biomaterial is directly applied onto the exposed pulp, whilst pulpotomy involves removal of a small portion (partial pulpotomy) or the complete removal of the coronal pulp tissue (full pulpotomy) after exposure, prior to application of the biomaterial and placement of a permanent restoration.

Available evidence

Two RCTs (Asgary et al., 2018; Bjørndal et al., 2010, 2017) with at least 12-month follow-up. One trial has published two reports at different time-points involving same cohorts (Bjørndal et al., 2010, 2017). Bjørndal et al. (2010) at 12 months follow-up reported 32.3% and 25.9% success for partial pulpotomy and direct pulp capping, respectively, with no difference between the groups (success was defined as pulp vitality without apical radiolucency). At 60 months, follow-up success decreases to 9.7% for partial pulpotomy and 3.7% for direct pulp capping (Bjørndal et al., 2017). On the other hand, Asgary et al. (2018) reported 40.8% success for partial pulpotomy, 56.5% for full pulpotomy and 61.6% for direct pulp capping at 12 months follow-up. The overall success rate from the study by Asgary et al. (2018) was a combination of clinical success (absence of signs/symptoms of inflammation/infection) and radiographic success. Postoperative pain was reported by Asgary et al. (2018) and no difference between the groups was noted.

Risk of bias

Low risk of bias for both RCTs (RoB 2). One study reported industry support, and one was supported by university funding.

Consistency

No meta-analysis could be performed due to the low number of studies and their heterogeneity in terms of methodology and reported success rates. Both included studies reported no difference between groups, although the effect size varied considerably between the two studies.

Clinical relevance and effect size

It is considered clinically relevant which treatment approach creates better conditions for the long-term preservation of a healthy pulp. The reported proportion of successful treatments varied greatly between the two included studies at 1 year; 62% (Asgary et al., 2018) and 26% (Bjørndal et al., 2010) for direct pulp capping. At 60 months, the proportion of successful treatments was less than 6% (Bjørndal et al., 2017). This variation brings some uncertainty but could be attributed to the fact that the comparison of partial pulpotomy and direct pulp capping was nested within a trial with another primary comparison in the Bjørndal study (Bjørndal et al., 2010).

Balance of benefits and harm

No data in included studies about harm directly related to procedures and no serious adverse effects were reported.

Ethical considerations

No obvious ethical issues.

Accessibility, affordability and equity issues

Direct pulp capping is considered a technically less demanding procedure compared with pulpotomy. However, for both procedures, an enhanced protocol including the use of aseptic conditions, magnification, disinfection of the exposed pulp and the use of suitable bioactive capping material has been recommended.

Legal considerations

No obvious ones.

Economic considerations

No cost-effectiveness analysis has been made based on a study directly comparing treatments. Initial costs would most likely be comparable for both treatment options, however, it is not possible to foresee whether there might be a higher cost for nonsuccessful cases of full pulpotomies as root canal treatment may be difficult to perform due to the formation of hard tissue at the canal orifices.

Patient preferences and values

There is no evidence supporting one approach over the other but a preference for a less invasive method would be more likely.

Applicability

There is a shortage of data for the treatment of older patient groups. Clinicians should be aware that the depth of the carious lesion and how the excavation is performed may affect the outcome of the treatments. Furthermore, studies have mainly been performed in university settings, which reduces the effectiveness and generalizability of the results.

Intervention

In teeth with caries in proximity to the pulp, the pulp may be exposed during operative treatment. Pulpotomy involves removal of a small portion (partial pulpotomy) or the complete removal of the coronal pulp tissue (full pulpotomy). Pulpectomy is a treatment with total removal of the pulp from the root canal system followed by root canal treatment, prior to placement of a permanent restoration. In cases of pulpitis associated with no or nonspontaneous pain when the pulp is cariously exposed, clinicians often prefer to carry out pulpectomy in assumption that the pulp is contaminated with bacteria, however, vital pulp treatment offers a less invasive treatment option.

Available evidence

One RCT (Galani et al., 2017) included 54 patients with deep caries randomly allocated to full pulpotomy or pulpectomy. Success was defined as combined clinical success (lack of pain, swelling and sinus tract and presence of intact restoration) and radiographic success (radiographs displayed PAI 1 at end of follow-up). Overall success rate was 81.5% in the pulpotomy group (full pulpotomy) and 77.8% in the RCTx group (pulpectomy) at 18-month follow-up, with no significant difference between groups (p > .05). No studies are currently available comparing partial pulpotomy with pulpectomy.

Risk of bias

RCT (Galani et al., 2017) with low risk of bias (RoB 2) but condition of the pulp is not precisely described. No statement of funding.

Consistency

Only one study was included.

Clinical relevance and effect size

It is considered clinically highly relevant which treatment approach creates better conditions for the long-term survival of the tooth. No reported difference between groups; proportion of successful treatments was 82% for full pulpotomy and 78% for pulpectomy at 18 months.

Balance of benefits and harm

No serious adverse effects were reported. Vital pulp treatment is generally considered quicker, less technically complex and less invasive than pulpectomy.

Ethical considerations

None.

Economic considerations

Pulpotomy (partial or full) is less costly and quicker to perform compared with pulpectomy. There are no data on cost-effectiveness of pulpotomy versus root canal treatment.

Patient preferences and values

No data are reported, but a preference for a less invasive method would be more likely.

Applicability

Evidence provided by only one study conducted in a well-controlled research environment; therefore, generalizability to general dental practice settings is unclear. Data are lacking on treatment of older-age groups.

Intervention

In cases of pulpitis associated with spontaneous pain, root canal treatment is considered by many clinicians to be the only choice of treatment to retain the tooth. Even though areas of bacterially infected or already necrotic tissue can be detected histologically beneath the carious lesion in the coronal pulp, this process does not affect the entire pulp tissue. Recent clinical studies have shown that high success rates may be achieved after partial or full pulpotomy. Partial pulpotomy is defined as removal of a small portion of coronal pulp tissue after exposure, followed by application of a biomaterial directly onto the remaining pulp tissue prior to placement of a permanent restoration. However, full pulpotomy is defined as complete removal of the coronal pulp and application of a biomaterial directly onto the pulp tissue at the level of the root canal orifice (s), prior to placement of the permanent restoration (ESE, 2019).

The studies included in the present SR performed one-visit root canal treatment with similar techniques. Instrumentation was performed with manual K-files, the working length was determined radiographically, whilst obturation was completed using cold lateral condensation (Asgary & Eghbal, 2010; Asgary et al., 2013, 2014, 2015). Eghbal et al. (2020) used rotary NiTi to prepare the canals, electronic apex locators/ radiographs to determine working length and obturation was carried out by cold lateral condensation.

In both studies, pulpotomy was performed with diamond burs in a high-speed handpiece. Haemorrhage control was achieved with saline in the Asgary et al.'s cohorts and with chlorhexidine (0.2%) and NaOCl (5.25%) in Eghbal et al.'s study. Calcium silicate cements were used in both studies, calcium-enriched mixture (CEM) was used as a pulp covering material in the Asgary et al's studies but Eghbal et al.'s study also included an MTA group. Permanent cavity filling was performed with dental amalgam 7 days after the pulpotomy in Asgary et al.'s cohort and a sandwich technique (glass–ionomer + light cured resin-bonded composite) was used in Eghbal et al.'s trial (Eghbal et al., 2020).

Available evidence

The systematic review (Tomson et al., 2022) included two RCTs (Eghbal et al., 2020; Asgary & Eghbal, 2010; Asgary et al., 2013, 2014, 2015). It is worth noting that one trial has published four reports at different time-points involving the same patient cohorts (Asgary et al., 2013, 2014, 2015; Asgary & Eghbal, 2010).

Postoperative pain meta-analysis revealed no difference in postoperative pain (day 7) between RCTx and pulpotomy (OR = 0.99, 95% CI 0.63–1.55, I² = 0%). Clinical success was high at year 1, 98% for both interventions, however, decreased over time to 78.1% (pulpotomy) and 75.3% (RCTx) at 5 years.

Risk of bias

Two RCTs with low risk of bias were available to study the ‘pain’ outcome (Asgary & Eghbal, 2010; Eghbal et al., 2020), whereas an RCT with high risk of bias (Asgary et al., 2013, 2014, 2015) was available to study ‘clinical and radiographic outcome’.

Consistency

Regarding postoperative pain outcome, meta-analysis was performed using two studies. The forest plot showed that I² statistic was 0%, which suggests that no heterogeneity was observed for the effect of two interventions (pulpotomy and root canal treatment). Regarding ‘clinical and radiographic’ outcomes, meta-analysis was not conducted because the studies have data from the same patient cohort published at different time-periods.

Clinical relevance and effect size

Considered as clinically relevant. No difference in postoperative pain (day 7) between RCTx and pulpotomy (OR = 0.99, 95% CI 0.63–1.55, I² = 0%). Clinical success was high at year 1, 98% for both interventions, however, decreased over time to 8.1% (pulpotomy) and 75.3% (RCTx) at 5 years.

Balance of benefits and harm

Vital pulp treatment including pulpotomy is generally quicker, less technically complex and less invasive than root canal treatment. It also reduces the risk of unwanted effects such as fracture, or residual periapical inflammation (ESE, 2019). There is a perception that root canal sclerosis could occur after pulpotomy, however, its prevalence is unknown and the degree to which it could prevent subsequent treatment to treat pulp necrosis or apical periodontitis cannot be predicted until longer-term clinical trials are conducted (Duncan et al., 2022).

Ethical considerations

None.

Accessibility, affordability and equity issues

Pulpotomy would be considered easier to perform than root canal treatment and therefore it would be anticipated it would be more widely available than root canal treatment which requires more time, greater expertise and more instruments to perform.

Legal considerations

None.

Economic considerations

Root canal treatment has additional costs compared to pulpotomy, which may not appear to be justified by the added benefits (Asgary et al., 2014).

Patient preferences and values

No data are reported. From the patient's perspective, pain control is an important issue. However, since both interventions (pulpotomy and root canal treatment) are equally effective in reducing postoperative pain, pain control does not seem to be a meaningful, determining factor in the choice of the final treatment approach.

Applicability

All included studies have been published by the same research group, involving patients from one country. Therefore, the generalizability of the results needs to be supported in future high-quality RCTs from other geographical regions. Both studies used calcium silicate cements for the biomaterial following pulpotomy, however, CEM was used in the Asgary et al. study cohort and this material is not available commercially currently in Europe.

Intervention

Root canal treatment is a ‘non-surgical’ approach used to treat two distinct endodontic disease entities: (1) ‘extirpation’ of vital, but ‘inflamed’ or ‘unsavable’ pulps, where the goal is to maintain existing periapical health and thus prevent periapical disease; this category also includes elective root canal treatment for prosthodontic reasons; or (2) the nonvital or dying, infected pulp, associated with radiographic signs of apical periodontitis. The goal of treatment for apical periodontitis is to restore the periradicular tissues to health. Additionally, the overall goal of root canal treatment is to ensure the survival and functionality of the teeth.

Available evidence

All 28 included studies were classified as cohort studies. Four of the five included studies, which reported on the outcome of tooth survival, showed pulp status is not a significant predictor (RR 1; 95% 1.00; n = 2 172 186 teeth). Presence of periapical radiolucency following RCTx in teeth with necrotic pulp was higher than teeth with vital pulp (RR 1.09; 95% CI 1.05, 1.13; n = 17 studies). In seven studies, no difference in postoperative pain in necrotic versus vital pulp was demonstrated. The quality of evidence for the outcome ‘tooth survival’ was considered to be moderate (one study of high RoB, one study of moderate RoB and one study of low RoB). The quality of evidence for the outcomes, ‘pain’ and ‘periapical health’, was considered to be moderate to high. The GRADE was dominated by the RoB and was not affected by heterogeneity; indirectness of evidence; imprecision; or publication bias.

Considerable heterogeneity amongst the included studies was obvious with regard to the periapical status of teeth with necrotic pulps, and criteria for determining ‘periapical health’ outcome. Statistical heterogeneity remained substantial after excluding data on teeth with necrotic pulp in the absence of radiographic signs of periradicular pathosis for analyses.

Risk of bias

Using the Risk of Bias 2.0. tool, one study (outcome ‘tooth survival’) was rated moderate risk of bias and two other studies (outcome ‘pain’ and ‘evidence of apical radiolucency’) were rated moderate-to-high risk of bias.

Consistency

The results from the different included studies are consistent.

Clinical relevance and effect size

Considered as clinically relevant. The CI was narrow in the meta-analysis (1.05, 1.13).

Balance of benefits and harm

Root canal treatment for teeth with vital and necrotic pulps is a predictable procedure when carried out to a high technical standard with no serious adverse effects reported by the reviewed studies. However, sodium hypochlorite accidents, extrusion of calcium hydroxide canal medicament or root filling material into the periapical tissues, maxillary sinus or inferior dental nerve canal have been reported to be associated with serious adverse effects (Alves et al., 2020; Gluskin et al., 2020; Guivarc'h et al., 2017; Yamaguchi et al., 2007).

Ethical considerations

The outcome data comparing root canal treatment on teeth with vital pulps versus necrotic pulps could only be obtained from observational studies because it is not ethically sound to electively devitalize and/or infect healthy teeth to generate randomized trial data.

Legal considerations

Pulp status should be confirmed to avoid overtreatment.

Economic considerations

The costs of root canal treatment on teeth with vital or necrotic pulps are comparable, although protocols may differ according to the pulp status. The setting will also influence costs and other economic considerations.

Patient preferences and values

No data are reported. It can be assumed that patients would rather not have root canal treatments in the absence of disease.

Applicability

In the majority of the included studies, the treatments were carried out in hospital or institution settings by undergraduate or postgraduate students under supervision and only some involved the primary care setting. Inference of the findings of the present systematic review can therefore not be necessarily drawn for the general dental practice setting, and in domiciliary setting which limits external validity. Furthermore, some earlier component studies used clinical techniques or materials not necessarily representative of contemporary practice.

Intervention

Immature permanent teeth with pulp necrosis with or without apical periodontitis pose particular technical challenges to the practitioner, as root morphology does not allow for conventional root canal treatment. Different treatment options are applied, which may be chosen, taking the stage of root development into account (Cvek, 1992). These include calcium hydroxide apexification, the apical plug technique and revitalization. Apexification refers to promoting the formation of a mineralized tissue barrier in teeth with an open apex and is considered suitable for Cvek stages II to IV. Calcium hydroxide has been used traditionally, where its repeated application led to the formation of an apical barrier which allowed for the subsequent root canal filling with Gutta–percha (Cvek, 1992; Kahler et al., 2014). After the introduction of hydraulic calcium silicate cements in endodontics, the apical plug technique was introduced as an alternative treatment (AAE, 2020). Revitalization as another treatment option was established more recently with benefits, particularly for Cvek stage I. The aim of the procedure is to create an environment to enable continued root formation. This may be achieved by triggering blood from the periapical area to clot in the root canal which can initiate the re-population of the pulp space with cells and subsequent formation of vital tissue (Wigler et al., 2013). Alternatively, mesenchymal stem cells could be transplanted inside the root canal (cell-based concept). The generally desired outcomes for revitalization are healing of periapical lesions, further root development and regaining of tooth sensitivity (AAE, 2018; Galler et al., 2016).

Available evidence

Two studies (Lin et al., 2017; Silujjai & Linsuwanont, 2017) addressed the PICO question, evaluating revitalization versus mineral trioxide aggregate (MTA) apical plug technique or calcium hydroxide apexification. Not all outcomes were addressed in the included studies. The most critical outcome was ‘survival’ and a combination of clinical and radiographical critical outcomes (absence of pain, tenderness, swelling, ‘radiographic evidence of reduction in apical lesion size’ and ‘radiographic evidence of increased root thickness and length’) was defined as ‘success’ in the current review. The survival and success rates seem to be high (76.5%–100%) during the first year after treatment and independent of the tooth and treatment type.

The additional outcome of sensitivity testing was not assessed in studies on immature permanent teeth.

Risk of bias

Survival after 12 months: Lin et al., 2017, and Silujjai & Linsuwanont, 2017, are both highly biased.

Success after 12 months: Lin et al., 2017, and Silujjai & Linsuwanont, 2017, are both highly biased.

Consistency

The studies differed in terms of study design, evaluation period, subject characteristics, treatment protocol and assessment method.

Clinical relevance and effect size

Effect size: <400 events = few events and hence not enough power to obtain a reliable level of certainty.

Clinical relevance: Due to limited evidence, revitalization may be considered a treatment option for apical periodontitis in immature permanent teeth.

Balance of benefits and harm

Revitalization may be a last resort for retention of very immature teeth (stages of root formation CVEK 1–2). This procedure offers a potential for root maturation, but still preserves options for future treatment due to retrievability; in cases of failure, all options to retreat still remain. Compared to calcium hydroxide apexification, there is a reduced number of visits. The apical plug technique similarly offers a reduced number of visits compared to calcium hydroxide apexification. The most frequently reported adverse event after revitalization was tooth discolouration due to the use of bismuth oxide-containing materials or other reasons (e.g blood, antibiotics).

Ethical considerations

For immature permanent teeth, revitalization is an established but not well-documented procedure.

Applicability

All clinical trials were conducted in well-controlled research settings and included specifically selected populations with no systemic diseases.

Intervention

With the objective of achieving biological regeneration of the dental pulp and providing a predictable and reproducible clinical outcome, researchers have made great efforts in recent years to develop tissue engineering strategies for application in the root canal. In this context, endodontic tissue engineering (ETE) can be subdivided into basic cell-based (CB-ETE) and primarily cell-free procedures (CF-ETE) (Widbiller & Schmalz, 2021; Dohan Ehrenfest et al., 2014; Lin et al., 2021). In the CB-ETE, the cells used must be expanded ex vivo and introduced into the root canal by transplantation into prefabricated scaffolds with added growth factors. In contrast, CF-ETE uses endogenous sources of stem or progenitor cells and bypasses ex vivo cell manipulation. Here, primarily cell-free scaffold materials are introduced into the root canal together with signalling molecules, where they are supposed to attract cells of the periapical tissue. A special application CF-ETE are autologous platelet products such as platelet-rich fibrin (PRF), platelet-rich growth factor (PRGF) or platelet-rich plasma (PRP), which can also be introduced in an orthograde direction into the root canal (Dohan Ehrenfest et al., 2014). Here, a fibrin matrix encapsulates blood components and platelets as a source of signalling molecules and, according to the concept of CF-ETE, provides the opportunity for cells to populate the root canal and form tissue.

Available evidence

One RCT (Xuan et al., 2018) addressed the PICO question, evaluating only approaches of cell-based endodontic tissue engineering. Survival after 12 months was reported. Furthermore, the study reported on pulp sensitivity and blood perfusion, however, it is not in a technically comparable form. Parameters of root maturation were addressed; radiographic evidence of periapical healing was also shown.

Risk of bias

Survival after 12 months: Xuan et al. (2018) with moderate concerns in terms of RoB.

Consistency

Not applicable due to only one study.

Clinical relevance and effect size

Effect size: <400 events = few events and hence not enough power to obtain a reliable level of certainty.

Clinical relevance: In patients with immature permanent teeth with pulp necrosis with or without apical periodontitis, CB-ETE may potentially be a valid treatment option.

Balance of benefits and harm

The study did not report on potential harm or adverse effects.

Ethical considerations

The possible advantages of endodontic tissue engineering with controllable risk together with the option to use the alternative therapy (calcium hydroxide apexification) in case of failure justify the treatment indication from an ethical perspective.

Applicability

The clinical trial (Xuan et al., 2018) was conducted in a well-controlled research setting and included specifically selected populations and age groups. In the underlying literature, only CB-ETE approaches were undertaken, limiting applicability to specialized facilities with appropriate equipment, expertise and authorization to perform cell transplantation. Therefore, generalizability of the results to general dental practice is not possible at this time.

Intervention

Treatment of patients diagnosed with apical periodontitis includes root canal preparation and chemo-mechanical debridement, which is accomplished with various types of instruments. Observable end-points of treatment are survival of teeth and postoperative pain (patient centred) and observable bony infill of apical radiolucent areas. Outcomes were compared between contemporary NiTi rotary instruments and classic techniques based on conventional stainless-steel hand instruments. Secondarily, differences in efficacy amongst various contemporary techniques were assessed.

Available evidence

The nine selected studies (Cheung & Liu, 2009; de Figueiredo, Lima, Lima, et al., 2020; Diniz-de-Figueiredo et al., 2020; Eyuboglu & Özcan, 2019; Fleming et al., 2010; Kandemir Demirci et al., 2021; Neves et al., 2020; Spili et al., 2005; Topçuoğlu & Topçuoğlu, 2017) included 1599 patients of which 1219 qualified for the systematic review. Three studies were retrospective studies (Cheung & Liu, 2009; Fleming et al., 2010; Spili et al., 2005) with overall good quality, whilst six of the studies were RCTs (de Figueiredo, Lima, Oliveira, et al., 2020; Diniz-de-Figueiredo et al., 2020; Eyuboglu & Özcan, 2019; Kandemir Demirci et al., 2021; Neves et al., 2020; Topçuoğlu & Topçuoğlu, 2017). Relative to the selected outcomes, five studies solely addressed the patient-centred outcomes survival (Fleming et al., 2010), quality of life (Diniz-de-Figueiredo et al., 2020) and postoperative pain (Eyuboglu & Özcan, 2019; Kandemir Demirci et al., 2021; Neves et al., 2020; Topçuoğlu & Topçuoğlu, 2017), three studies addressed periapical healing (Cheung & Liu, 2009; Spili et al., 2005), whilst one study included both outcomes (de Figueiredo, Lima, Lima, et al., 2020). A meta-analysis limited to three studies that addressed PICOT 1 and radiographic outcomes were performed (Cheung & Liu, 2009; de Figueiredo, Lima, Lima, et al., 2020; Spili et al., 2005).

The majority of studies (6/9) (Cheung & Liu, 2009; Diniz-de-Figueiredo et al., 2020; Fleming et al., 2010; Neves et al., 2020; Spili et al., 2005; de Figueiredo, Lima, Lima, et al., 2020) compared various forms of contemporary treatment in a variety of clinical scenarios with classic procedures defined as manual preparation with stainless-steel files. Two further studies (Eyuboglu & Özcan, 2019; Kandemir Demirci et al., 2021) provided outcome data comparing different forms of contemporary root canal preparation, such as rotary versus reciprocation or different types of contemporary instruments, whilst one study addressed both clinical questions.

Risk of bias

The retrospective studies (Cheung & Liu, 2009; Fleming et al., 2010; Spili et al., 2005) were judged as overall of good quality, whilst each of the three RCTs had a high risk of bias (de Figueiredo, Lima, Lima, et al., 2020; Diniz-de-Figueiredo et al., 2020; Eyuboglu & Özcan, 2019) or some concerns were noted (Kandemir Demirci et al., 2021; Neves et al., 2020; Topçuoğlu & Topçuoğlu, 2017). There was unclear publication bias in 3/6 reports for the RCTs (de Figueiredo, Lima, Lima, et al., 2020; Diniz-de-Figueiredo et al., 2020; Topçuoğlu & Topçuoğlu, 2017).

Consistency

Evidence was fragmented overall and only few data points were available for certain outcomes and comparisons, therefore the overall quality of evidence was considered moderate or weak. Patient-reported or -centred outcomes were inconsistently reported, however, adverse events, when reported, were rare. Study heterogeneity was high.

Clinical relevance and effect size

Survival: Current evidence suggested a benefit for contemporary over traditional root canal preparation techniques in terms of survival without post-treatment intervention (odds ratio = 0.13 [95% CI = 0.04–0.47]) from a retrospective study that included 289 patients (Fleming et al., 2010).

Oral health-related quality of life: Currently, there is weak evidence analysing OHIP-14 scores for a more favourable outcome in patients who received a root canal treatment using contemporary instrumentation with NiTi instruments (46 patients) compared with the classic group using stainless-steel hand instruments (42 patients) after 6 months. At 12-month follow-up, there were no differences between the contemporary and classic techniques, which included 42 and 45 patients respectively. Also, root canal filling techniques differed amongst groups (Diniz-de-Figueiredo et al., 2020).

Pain: Current evidence suggests that any type of mechanized root canal instrumentation with NiTi instruments may reduce postoperative pain after retreatment. No difference in pain score was seen amongst studies 1-week post-treatment, except for one study with high risk of bias (Topçuoğlu & Topçuoğlu, 2017).

Radiographic healing: Current evidence suggests a benefit for contemporary over traditional root canal preparation techniques. The results of the meta-analysis based on three studies (Cheung & Liu, 2009; de Figueiredo, Lima, Lima, et al., 2020; Spili et al., 2005) with 332 evaluable participants showed that contemporary instrumentation improved radiographic healing (p = .005) compared with traditional root canal preparation with stainless-steel instruments (odds ratio = 2.07 [95% CI = 1.25–3.44]) with no evidence of statistical heterogeneity (I² = 0%).

Current evidence is weak when suggesting that the use of reciprocating instrumentation in root canal retreatment may be associated with a higher intensity of postoperative pain. This statement is based on an RCT that showed a significantly higher intensity of postoperative pain in retreatment (p = .001) performed with reciprocating instrumentation (33 patients) up to day 7 when compared with different rotary instruments (66 patients) (Eyuboglu & Özcan, 2019). Other RCTs reported no significant differences between multifile rotary versus reciprocating single file for primary endodontic treatment (103 patients) (Kandemir Demirci et al., 2021) or retreatment (70 patients) (Topçuoğlu & Topçuoğlu, 2017). The overall effect size of the instrument type selected appears small.

Balance of benefits and harm

The majority of the studies did not report on potential harm/adverse effects.

Ethical considerations

Additional cost of nickel–titanium root canal instruments may be justified; reprocessing issues should be considered.

Applicability

The majority of studies were conducted in well-controlled research environments and included specifically selected populations, that is, those with no systemic diseases. Moreover, different operator competence levels were evident. However, the majority of the studies were performed by endodontic specialists. This appears to reduce applicability or external validity to different provider competence levels. The evidence presented illustrates ‘efficacy’ rather than ‘effectiveness’; therefore, generalizability to general dental practice settings is unclear.

Intervention

In association with chemo-mechanical root canal preparation with instruments, different types and/or concentrations of irrigant solutions have been suggested to improve outcomes for root canal treatment of teeth with an infected root canal system and apical periodontitis.

Available evidence

Two RCTs addressed the PICOTS question. One study involving 126 patients evaluated different types of irrigants: 5.25% sodium hypochlorite (NaOCl) and a mixture of 2% chlorhexidine gel and normal saline in association with 17% EDTA (Almeida et al., 2012). The other study, involving 86 patients evaluated the effect of different concentrations of NaOCl (1% and 5%) in association with 17% EDTA (Verma et al., 2019). Radiographic healing was reported in one study (Verma et al., 2019), whilst pain after 7 days was reported in two RCTs (Almeida et al., 2012; Verma et al., 2019). Meta-analysis was not performed.

Risk of bias

One RCT had low risk of bias, and one had some concerns.

Consistency

Study reporting was consistent with respect to pain. Only one study reported on radiographic healing.

Clinical relevance and effect size

Radiographic healing: One RCT assessed periapical healing at 1 year after root canal treatment using the Periapical Index. An overall healing rate of 76.7% (66/86) was reported. In the high-concentration (5% NaOCl) group, 81.4% healed, and in the low-concentration group, 72.1% healed, but the difference was not statistically significant (p > .05) (Verma et al., 2019).

Pain: Two RCTs assessed pain after 7 days, and in both studies, no patients reported severe pain at any postoperative time interval (Almeida et al., 2012; Verma et al., 2019). After 7 days, no patients (Verma et al., 2019), or only a few patients (Almeida et al., 2012), experienced even mild pain, with no significant difference between the groups. In one study, 20%–24% of patients required analgesics; however, there was no significant difference between groups (Verma et al., 2019). There is currently insufficient evidence to recommend any type and concentration of irrigant over another for the treatment of apical periodontitis or management of postoperative pain.

Survival and other outcomes were not reported in any included study.

Balance of benefits and harm

None of the included studies reported on potential harm/adverse effects.

Ethical considerations

As the use of inert irrigation solutions alone, such as water or saline, may be considered unethical, this could contribute to a relative scarcity of studies on irrigation solutions.

Applicability

The studies were conducted in well-controlled research environments and included specifically selected subpopulations, for example, with no systemic diseases (i.e. ‘no relevant comorbid conditions’ ‘immunocompromised or immunosuppressed’) (Almeida et al., 2012) or ‘diabetes, immunocompromised patients’ (Verma et al., 2019). Moreover, different operator competence levels were evident. This appears to reduce applicability to different provider competence levels. The evidence presented illustrates ‘efficacy’ rather than ‘effectiveness’; therefore, generalizability to general dental practice settings is unclear.

Intervention

Treatment of patients diagnosed with asymptomatic apical periodontitis may include, in addition to chemo-mechanical canal preparation, the use of various inter-appointment medicaments, with the aim of improving overall debridement and disinfection.

Available evidence

Four studies, all RCTs, reported on use of inter-appointment medication when treating asymptomatic apical periodontitis (Paredes-Vieyra & Jimenez-Enriquez, 2012; Peters & Wesselink, 2002; Waltimo et al., 2005; Weiger et al., 2000). Three studies compared single-visit treatment with multiple visits including inter-appointment medication in the form of calcium hydroxide, powder or mixed with water (Paredes-Vieyra & Jimenez-Enriquez, 2012; Peters & Wesselink, 2002; Weiger et al., 2000). All four studies reported on periapical healing, of which three used strict radiographic criteria and were sufficiently homogenous to be further synthesized via meta-analysis and showed a low statistical heterogeneity.

Risk of bias

One study was assessed to have low risk of bias, and three to have some concerns.

Consistency

Consistency was demonstrated across the studies, even though only one study individually showed a significant effect (Paredes-Vieyra & Jimenez-Enriquez, 2012).

Clinical relevance and effect size

It was demonstrated that there was a benefit for single-visit root canal treatment [without Ca(OH)₂] compared with multiple-visit root canal treatment [with Ca(OH)₂] in relation to radiographic healing using strict criteria (RR 1.10; 95% CI 1.03–1.19: p = .007).

Balance of benefits and harm

From a patient's point of view, there is a benefit of one visit compared to several visits in relation to discomfort, time and economy. The majority of the studies did not report on potential harm/adverse effects. The use of calcium hydroxide in case of extrusion may be associated with adverse effects based on case reports (Gluskin et al., 2020).

Ethical considerations

No relevant ethical considerations were identified.

Applicability

The majority of studies were conducted in well-controlled research environments and two included specifically selected populations that is those with no systemic diseases (i.e. ‘non-contributory medical history’ [Peters & Wesselink, 2002]; ‘patients in good health’ [Paredes-Vieyra & Jimenez-Enriquez, 2012]). The studies included only teeth with asymptomatic apical periodontitis, and findings therefore do not apply to treatment of acute apical periodontitis. Operator expertise was not disclosed, which reduces the applicability of the data to different provider competence levels. The evidence presented illustrates ‘efficacy’ rather than ‘effectiveness’; therefore, generalizability to general dental practice settings is unclear.

Intervention

After chemo-mechanical debridement of the root canal system, treatment of patients diagnosed with apical periodontitis includes root canal filling, accomplished with various materials and clinical techniques. Observable end-points of treatment are retention of teeth in function (survival) and postoperative pain as well as observable bone fill of apical radiolucent areas described based on semi-quantitative or qualitative measures. Outcomes were contrasted between lateral compaction of Gutta–percha with epoxy resin sealer and other clinical techniques. Secondarily, differences in efficiency amongst various sealers were assessed.

Available evidence

Ten studies were included. Nine prospective studies included 709 teeth (Chu et al., 2005; de Figueiredo, Lima, Lima, et al., 2020; de Figueiredo, Lima, Oliveira, et al., 2020; Diniz-de-Figueiredo et al., 2020; Graunaite et al., 2018; Kandemir Demirci & Çalışkan, 2016; Michanowicz et al., 1989; Özer & Aktener, 2009; Wong et al., 2015) and one retrospective study included 177 teeth (Aqrabawi, 2006). Eight studies were RCTs, including in total 651 teeth (de Figueiredo, Lima, Lima, et al., 2020; de Figueiredo, Lima, Oliveira, et al., 2020; Diniz-de-Figueiredo et al., 2020; Graunaite et al., 2018; Kandemir Demirci & Çalışkan, 2016; Michanowicz et al., 1989; Özer & Aktener, 2009; Wong et al., 2015).

Relative to the respective selected outcomes, seven studies addressed various patient-centred outcomes such as survival and postoperative pain, eight addressed a combination of periapical healing and clinical symptoms, whilst one study included both outcomes. The majority of studies (9/10) compared various root canal filling techniques to lateral compaction. Two further data sets provided outcome data comparing different types of sealers used for root canal filling.

Risk of bias

Nine studies were found to be at a high risk of bias, and one study had some concerns (Kandemir Demirci & Çalışkan, 2016). There was unclear publication bias in all reports.

Consistency

Evidence was overall fragmented and only few data points were available for some outcomes and comparisons, therefore the overall quality of evidence was considered moderate or weak. Patient-reported outcomes were inconsistently reported, however, adverse events, when reported, were rare. Study heterogeneity was high.

Clinical relevance and effect size

Survival: Current evidence suggested that tooth survival was similar in teeth treated using lateral compaction and a carrier-based system from a prospective study that included 58 teeth (Chu et al., 2005). Four teeth in the lateral compaction group and three teeth in the carrier-based group—a total of seven teeth—were extracted due to fracture before recall examination but it is not known whether these teeth had preoperative AP. All other studies did not report information on extracted teeth.

Radiographic healing: Current evidence suggested similar outcomes for nonlateral compaction techniques over cold lateral compaction techniques using Gutta–percha. The results of the systematic review based on seven studies with 385 evaluable teeth showed that any type of no lateral compaction technique did not improve radiographic healing compared to cold lateral compaction technique using Gutta–percha.

Current evidence did not suggest any consistent effect of varying sealer types on radiographic healing from a prospective study that included 177 teeth (Aqrabawi, 2006). Six of seven studies (n = 385) showed no significant difference (Chu et al., 2005; de Figueiredo, Lima, Lima, et al., 2020; Diniz-de-Figueiredo et al., 2020; Kandemir Demirci & Çalışkan, 2016; Michanowicz et al., 1989; Özer & Aktener, 2009).

Pain: Current evidence suggested that neither varying root canal filling techniques (from 3 prospective studies with 409 evaluable teeth; Diniz-de-Figueiredo et al., 2020; Kandemir Demirci & Çalışkan, 2016; Wong et al., 2015) nor the sealer type (from 1 RCT with 57 patients; Graunaite et al., 2018) resulted in different incidence of postoperative pain.

Sealers of various types, for example, epoxy resin, ZOE based or calcium silicate based, were tested and the overall effect size of sealer type on investigated outcomes appears to be limited.

Balance of benefits and harm

Nine studies did not report on potential harm/adverse effects. One study showed a higher risk of overfilling in relation to carrier-based technique but did not show any difference in outcome. Time required for root canal filling may be relevant for the patient.

Ethical considerations

Cost of materials should be considered.

Applicability

The majority of studies were conducted in well-controlled research environments and included specifically selected populations, that is, those with no systemic diseases. Moreover, different operator competence levels were evident. This appears to reduce applicability to different provider competence levels. The evidence presented illustrates ‘efficacy’ rather than ‘effectiveness’; therefore, generalizability to general dental practice settings is unclear.

Intervention

After chemo-mechanical root canal preparation with instruments and traditionally delivered irrigants, different forms of adjunct therapy have been investigated to optimize root canal cleaning and disinfection. These include irrigant activation methods/devices, light-mediated root canal disinfection (photo-activated disinfection and direct laser irradiation) and ozone therapy. Adjunct therapy has been suggested to improve treatment outcomes after root canal treatment of teeth with an infected root canal system.

Available evidence

Fourteen studies (13 RCTs and 1 retrospective cohort) addressed the PICO question, evaluating different types of adjunct therapy: antimicrobial photodynamic therapy (aPDT) (3 RCTs: [Barciela et al., 2019a; Guimarães et al., 2021; Souza et al., 2021]), diode laser canal irradiation (2 RCTs: [Kaplan et al., 2021; Morsy et al., 2018]), 1 retrospective cohort: (Masilionyte & Gutknecht, 2018), Nd:YAG laser canal irradiation (2 RCTs: [Koba et al., 1999, Verma et al., 2020]), Er:Cr:YSGG laser canal irradiation (one RCT: [Martins et al., 2014]), ozone therapy (2 RCTs: [Kist et al., 2017; Pietrzycka & Pawlicka, 2011]) and ultrasonically activated irrigation (UAI) (4 RCTs: [Liang et al., 2013; Middha et al., 2017; Tang et al., 2015; Verma et al., 2020]).

Radiographic healing was reported in seven studies, but meta-analysis was only possible for two RCTs investigating the use of UAI (Liang et al., 2013; Verma et al., 2020) and two RCTs investigating ozone therapy (Kist et al., 2017; Pietrzycka & Pawlicka, 2011); none of them showed any difference between intervention and control. The other trials (Martins et al., 2014; Masilionyte & Gutknecht, 2018; Tang et al., 2015) did not find any significant difference either.

Pain after 7 days was reported in seven RCTs. Meta-analysis was performed on three studies that used aPDT (Barciela et al., 2019a; Guimarães et al., 2021; Souza et al., 2021), and on two studies using diode laser irradiation (Morsy et al., 2018; Kaplan et al., 2021). None of the meta-analytic estimates showed a difference between intervention and control. Middha et al. (2017) found no difference in pain after 7 days between UAI and control, whilst Tang et al. (2015) reported significantly lower pain levels in the UAI group.

Risk of bias

Radiographic healing: three RCTs had high risk of bias, two had some concerns and only one had low risk of bias.

Pain: four RCTs had high risk of bias, two had some concerns and one had low risk of bias.

Consistency

Studies differed in terms of type of adjunct therapy, practical details of applied adjunct therapy (such as laser wavelength, type of photosensitizer and irradiation/activation time), outcome determination (e.g. clinical vs. radiographic success, strict vs. loose radiographic criteria) and several possible combinations of these. Within the same adjunct therapy, consistency was demonstrated across the studies.

Clinical relevance and effect size

Radiographic healing: The lesion reduction after 12 months in the ultrasonically activated irrigation group was 12% higher than in the control group; this was, however, not statistically significant (RD = −0.12; 95% CI: −0.25–0.02, p = .09). Two studies investigating the use of ozone, also showing no statistically significant difference (RD = −0.04; 95% CI: −0.23–0.16, p = .72). One RCT investigating Er;Cr:YSGG laser showed no significant difference in healing after 12 months. One cohort study (940 nm diode laser) showed no significant difference in healing after longer observation times.

Pain: Meta-analysis on three studies that used aPDT, and on two studies using diode laser irradiation showed no significant difference in the prevalence of pain after 7 days between the control and adjunct therapy—(RD = −0.07; 95% CI: −0.27–0.13, p = .51) and (RD = −0.03; 95% CI: −0.11–0.06, p = .50) respectively. One individual RCT (UAI) showed no significant difference (p = .154). One cohort study (UAI) indicated more pain after 7 days in the control group (p < .05).

There is currently insufficient evidence to recommend any adjunctive therapy for the treatment of apical periodontitis or management of pain occurring after 7 days.

Balance of benefits and harm

None of the studies reported on potential harm/adverse effects.

Ethical considerations

Additional costs associated with adjunctive therapy may not be justified in the absence of benefit for the patient.

Applicability

Most studies were conducted in well-controlled research environments and included specifically selected populations that is those with no systemic diseases. Moreover, different operator competence levels were evident. This appears to reduce applicability to different provider competence levels. The evidence presented illustrates ‘efficacy’ rather than ‘effectiveness’; therefore, generalizability to general dental practice settings is unclear.

Intervention

The gold standard for treating mature permanent teeth with pulp necrosis with or without apical periodontitis is root canal treatment. Nevertheless, revitalization, a treatment established for immature permanent teeth, has been explored also for mature teeth more recently. The treatment may enable good bony healing and a biological root canal filling (Glynis et al., 2021).

Available evidence

Two RCTs (Arslan et al., 2019; Jha et al., 2019) addressed the PICO question, evaluating revitalization versus root canal treatment. Not all outcomes were addressed in all included studies. The most critical outcome was ‘survival’ and a combination of clinical and radiographical critical outcomes (pain, tenderness, swelling and ‘radiographic evidence of reduction in apical lesion’) was defined as ‘success’ in the current review. The survival and success rates reported in these two studies seem to be high (≥80%) during the first year after treatment independent of the tooth and treatment type.

The additional outcome ‘Sensitivity Testing’ was not assessed by Jha et al., 2019 (16), but in Arslan et al., 2019, it was positive in 50% of the revitalized teeth. Brizuela et al., 2020, were also included in this systematic review, assessing revitalization in mature permanent teeth. Nevertheless, this study was excluded from the current recommendation, as it is a Phase I/II study (assessing safety and efficacy) and was not performed to present the superiority of this treatment approach in mature teeth.

Risk of bias

Success after 12 months: Two RCTs, Arslan et al., 2019 (15) and Jha et al., 2019 (16), both highly biased.

Consistency

Studies differed in terms of study design, subject characteristics, treatment protocol, assessment method and study outcome.

Clinical relevance and effect size

Balance of benefits and harm

Ethical considerations

Revitalization of mature permanent teeth seems to be experimental so far.

Applicability

All clinical trials were conducted in well-controlled research settings and included specifically selected populations with no systemic diseases.

Intervention

Apical surgery consists of periapical curettage, root-end resection/apicectomy, root-end preparation and root-end filling for the management of teeth with apical periodontitis following nonsurgical root canal treatment and when nonsurgical root canal retreatment is impractical or offers a poorer prognosis. However, the studies identified did not employ comparable surgical techniques that meet the currently accepted clinical standards.

Available evidence

Five studies (2 RCTs, 2 NRCTs and 1 retrospective cohort) addressed the PICOT question, evaluating root canal treatment or retreatment versus apical surgery. These studies showed large heterogeneity in many aspects, from the study protocol to the materials and techniques used, as well as in the radiographic evaluation. The included studies did not mention clinical aspects such as the initial size of the periapical lesion, the quality of the previous root canal treatment and the coronal restoration, or the training of the operator.

Tooth survival was reported in three studies (1 RCT and 2 NRCTs), but meta-analysis was not possible (Estrela et al., 2014; Prati et al., 2018; Riis et al., 2018).

Radiographic healing was reported in four studies (1 RCT, 2 NRCTs and 1 retrospective cohort study), but meta-analysis was not possible (Danin et al., 1996; Liu et al., 2021; Prati et al., 2018; Riis et al., 2018).

Need for further intervention was reported in three studies (1 RCT, 1 NRCT and 1 retrospective cohort study), but meta-analysis was not possible (Danin et al., 1996; Estrela et al., 2008; Liu et al., 2021).

Presence of symptoms (issues related to OHRQoL) was reported in one study (1 RCT), but meta-analysis was not possible (Danin et al., 1996). Further controlled clinical trials comparing the clinical and patient-related outcomes of apical surgery, nonsurgical root canal treatment or retreatment are still needed.

Risk of bias

Tooth survival: Two studies with high risk of bias (NRCT) and one with moderate risk of bias (RCT).

Radiographic healing: All studies had high risk of bias (1 RCT, 2 NRCTs and 1 retrospective cohort study).

Need for further intervention: Two studies had high risk of bias (1 NRCT and 1 retrospective study) and one had moderate risk of bias (1 RCT).

Presence of symptoms (issues related to OHRQoL): The one study had high risk of bias (1 RCT).

Consistency

The consistency of the studies is uncertain since confidence intervals of effect estimates were not reported.

Clinical relevance and effect size

Due to heterogeneity, no meta-analysis was possible for any outcome.

Tooth survival: 84.04% of teeth in the experimental group versus 88.19% in the control group (No. of patients at follow-up = 229).

Need for further intervention: 7.1% of teeth in the experimental group versus 18.3% in the control group (No. of patients at follow-up = 357).

Radiographic healing (complete or partial) 1 year after treatment: 82.9% of teeth in the experimental group versus 71.7% in the control group (No. of patients at follow-up = 408).

Oral health-related quality of life (presence of symptoms): 5.3% of teeth in the experimental group versus 22.2% in the control group (No. of patients at follow-up = 37).

Balance of benefits and harm

The studies did not report on potential harm/adverse effects, so no conclusion can be drawn.

Ethical considerations

No ethical considerations were detected.

Applicability

All of the studies were conducted in university or academic dental clinical settings. The majority of the studies did not report on the clinicians' experience or the patients' general health status, so this reduces applicability.

Intervention

Root resection or root amputation techniques are defined as the complete removal of an entire root and of the surrounding adherent soft tissues, leaving the crown intact and supported by other remaining roots. Hemisection is the procedure where the root is resected and removed with the corresponding portion of the crown, as it can happen in maxillary and mandibular molars. The procedure was reported for the management of teeth with periodontal involvement of the furcation, or apical periodontitis involving a single root in a multi-rooted tooth, with the aim of tooth retention, when other treatments were not considered feasible or had failed.

Available evidence

The systematic review on the topic (Corbella et al., 2022) reported that no comparative randomized or nonrandomized trials were available for the addressed comparisons. Sparse data were extracted and considered from three papers on retrospective case series (Alassadi et al., 2020; Derks et al., 2018; El Sayed et al., 2020) that reported clinical outcomes after root resection was performed for endodontic reasons. The validity of the available results, which are just partly focussed on the objective of the review, is substantially limited by the presence of confounding factors; such as the extent of periodontal involvement, heterogeneity of the study protocols and insufficient information about the endodontic status of the samples. Clinical trials comparing the effectiveness of root resection techniques with nonsurgical root canal retreatment or apical surgery are required.

Risk of bias

The assessment of the risk of bias in the studies found that two papers were classified as low quality (Alassadi et al., 2020; Derks et al., 2018), and one study was classified as moderate quality (El Sayed et al., 2020). No funding bias was found in relation to these three studies.

Consistency

The consistency of the studies is uncertain since confidence intervals of effect estimates were not reported.

Clinical relevance and effect size

Tooth survival: The studies included in the review consisted of data from 305 resected teeth, from 254 patients, with a follow-up period of 1–16.8 years. Overall, 151 teeth were extracted during the follow-up period. In these studies, root resection treatment was carried out on 42 teeth exclusively for endodontic reasons.

Balance of benefits and harm

The studies did not report on potential harm/adverse effects. However, whilst it allows for the potential of tooth retention, root resection techniques are surgical procedures that weaken tooth structure, potentially risking tooth/root fracture and prosthodontic failure.

Ethical considerations

No ethical considerations were detected.

Applicability

The applicability of root resection technique should be weighted by considering the periodontal condition of the teeth (periodontal attachment loss and furcation involvement), which was not acknowledged in the studies included in the review by Corbella et al. (2022).

Intervention

Intentional replantation entails intentional atraumatic tooth extraction, extra-alveolar evaluation of the root surfaces and endodontic management, followed by re-insertion of the tooth into its original position in the tooth socket. If needed, intentional replantation can also be combined with surgical extrusion, the repositioning of the tooth more coronally than its original position. Intentional replantation is a treatment option for permanent teeth with apical periodontitis that have not responded favourably following nonsurgical root canal treatment/retreatment or apical surgery.

Available evidence

None of the studies fulfilled the selection criteria. Therefore, we do not know the effectiveness of intentional replantation when compared with nonsurgical root canal treatment/retreatment or apical surgery in terms of clinical and patient-related outcomes in managing permanent teeth with apical periodontitis. Clinical trials comparing the effectiveness of intentional replantation with nonsurgical root canal treatment/retreatment or apical surgery are required. Despite being excluded, four noncomparative clinical studies (Cho et al., 2016; Choi et al., 2014; Jang et al., 2016; Wu & Chen, 2021) reported high overall survival rates in the mid-to-long term, with relatively low complication rates.

Risk of bias

None of the studies fulfilled the selection criteria. Hence, the risk of bias analysis was not performed.

Consistency

None of the studies fulfilled the selection criteria. Hence, the consistency cannot be assessed.

Clinical relevance and effect size

No effect size could be determined as no studies were included.

Balance of benefits and harm

There are certain risks associated with intentional replantation, such as tooth fracture during extraction, periodontal breakdown or possible future root resorption (mainly replacement root resorption or ankylosis), that are not objectively controllable. If anatomical conditions permit atraumatic extraction and an extraoral time of less than 15 minutes, then intentional replantation can be considered for the management of apical periodontitis, thereby preserving the tooth.

Ethical considerations

No ethical considerations were detected.

Economic considerations

Intentional replantation can be an alternative to tooth extraction and implant placement, thus potentially reducing the comparative costs for patients.

Patient preferences and values

In the absence of high-quality evidence from comparative clinical trials (CCTs), clinical decision-making should be on a case-by-case basis and in accordance with the clinician's experience and the patient's preference.

Applicability

Clinical studies showed that intentional replantation may be a treatment modality to manage problems of endodontic origin.