Efficacy of 4% articaine vs 2% lidocaine in mandibular and maxillary block and infiltration anaesthesia in patients with irreversible pulpitis: a systematic review and meta-analysis

Protocol development

This systematic review and meta-analysis are written and reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement and registered in PROSPERO (CRD42020204606). The following focused question in the Patient, Intervention, Comparison, and Outcome (PICO) format was proposed “Is there a difference in the efficacy of 4% articaine vs 2% lidocaine in the mandibular and maxillary block and infiltration anaesthesia in patients with IP?”

Search strategy

To obtain publications in the English language, a complete electronic search was conducted through July 2020 on databases such as PubMed and MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science. A detailed electronic search of the journals listed in Table 1 was carried out. The searches in the clinical trials database, cross-referencing and Grey literature were conducted using Google Scholar, Greylist, and OpenGrey.

Articles were found using Medical Subject Headings (MeSH) terms, keywords, and other free terms coupled with Boolean operators (OR, AND). Following the syntactic guidelines of each database, the same terms were utilised across all search platforms. Table 1 shows the search strategy, population, interventions, comparisons, outcomes, and study design (PICOS) tool.

Inclusion criteria outline according to the PICOS strategy

Population (P):

Studies on patients with symptomatic IP, requiring endodontic treatment under maxillary and mandibular infiltration or blocked anaesthesia on at least one tooth in the mandibular or maxillary region irrespective of age, gender, race, or socioeconomic status, were evaluated. Active responses to spontaneous pain, thermal tester, cold tester, or an electronic pulp tester were considered as diagnostic criteria for IP.

Interventions (I): Studies using 4% articaine as a LA solution for the treatment of IP.

Comparison (C): Studies using 2% lidocaine as a LA solution for the treatment of IP.

Outcome (O): Primary outcome: It included the success rate assessed as ‘no/mild’ pain during access cavity preparation and biomechanical preparation phase on the Heft Parker visual analogue scale (VAS).

Secondary outcome: Onset of anaesthesia assessed from the time lapse between the end of the NB and the onset of symptoms of subjective anaesthesia (feeling of heaviness at the site of injection) were calculated in seconds, and the pain was assessed quantitatively during the treatment.

Study design (S): In vivo studies, clinical trials, RCTs, cluster randomised trials, quasi-experimental studies and non-randomised trials (NRS).

Exclusion criteria

• Studies involving patients with a significant medical history or on medicaments that may affect the anaesthetic assessment.

• Observational study designs, case reports, case series, cross-sectional studies, and reviews.

• Trials reporting a single intervention.

• Article reporting only abstracts and full-texts were not available in the database.

Screening process

Two reviewing authors did the search and screening according to the previously stated methodology (SP & AM). The titles and abstracts were examined first. Second, full-text publications were picked for in-depth reading and analysis based on the data extraction criterion’s inclusion and exclusion criteria. Cohen’s kappa (k) determined the degree of agreement between the two reviewers to be 0.94 for titles and abstracts and 0.96 for full-texts. After discussions, the third author SM was able to reconcile the disagreements among the authors/reviewers. The authors of the listed papers were contacted via email for clarification of any concerns or missing data.

Data extraction

The two independent authors (IA & BA) extracted the following data from the included studies: author names, study design, tooth, sample size, method of pulp testing, type of local anaesthesia used, injection technique, method of analysis, method of outcome assessment, follow-up and author’s conclusions.

Assessments of the risk of bias and quality

The level of evidence for included studies was assessed using the Joanna Briggs Institute (JBI) level of evidence (The Joanna Briggs Institute, 2014). The quality of the selected studies was assessed using the Cochrane Collaboration Tool (Higgins et al., 2019) for RCTs, including random sequence generation, allocation concealment, blinding of participants, incomplete outcome data, selective reporting, and other biases. The quality of NRS was assessed using the Minors checklist (Slim et al., 2003), wherein the minimum outcome assessment time of 5 min was considered appropriate for the included studies.

Statistical analysis

Review Manager (RevMan) 5.3 was used for statistical analysis. The combined results were expressed as relative risks (RRs) for the dichotomous data at 95% confidence intervals (CIs) and P < 0.05 was considered significant. Statistical heterogeneity was assessed by the I² test at α = 0.10. Subgroup analysis was conducted for I² > 50% and P ≤ 0.10. For I² > 50%, the random-effects model was applied. Sensitivity analysis was conducted to assess the stability of the results. Funnel plots were drawn to detect publication bias for studies exceeding 10 in number for each outcome assessed (Su et al., 2016).

Literature search

The PRISMA statement flowchart summarising the selection process is presented in Fig. 1. Among 33 full-text articles, 26 were selected after pre-screening, applying the eligibility criteria, and addressing the PICOS question. Seven studies were excluded as three did not have a control group, three had inappropriate population variables, and one applied intraosseous injection technique, hence only 26 studies were included in the qualitative analysis, whereas 22 out of 26 studies for quantitative synthesis.

Study characteristics

The general characteristics of 26 studies (Gao & Meng, 2020; Kumar et al., 2020; Aggarwal et al., 2019; Ghazalgoo et al., 2018; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Shapiro et al., 2018; Aggarwal, Singla & Miglani, 2017; Umesh, 2017; Allegretti et al., 2016; Hosseini et al., 2016; Saraf et al., 2016; Zain et al., 2016; Monteiro et al., 2015; Rajput et al., 2015; Ahmad et al., 2014; Nabeel, Ahmed & Sikander, 2014; Rogers et al., 2014; Sood, Hans & Shetty, 2014; Ashraf et al., 2013; Tortamano et al., 2013; Kanaa, Whitworth & Meechan, 2012a; Kanaa, Whitworth & Meechan, 2012b; Aggarwal et al., 2011; Poorni et al., 2011) are presented in Table 2. All included studies were unicentric trials published between 2011 and 2020. Of the 26 studies, 10 studies (Kumar et al., 2020; Aggarwal et al., 2019; Lokhande et al., 2019; Aggarwal, Singla & Miglani, 2017; Umesh, 2017; Saraf et al., 2016; Sood, Hans & Shetty, 2014; Subbiya et al., 2011; Aggarwal et al., 2011; Poorni et al., 2011) were conducted in different parts of India, 3 in Iran (Ghazalgoo et al., 2018; Hosseini et al., 2016; Ashraf et al., 2013), Pakistan (Zain et al., 2016; Rajput et al., 2015; Nabeel, Ahmed & Sikander, 2014) and Brazil (Allegretti et al., 2016; Monteiro et al., 2015; Tortamano et al., 2013), 2 in the USA (Shapiro et al., 2018; Rogers et al., 2014), 2 in the UK (Kanaa, Whitworth & Meechan, 2012a; Kanaa, Whitworth & Meechan, 2012b) and one each in China (Gao & Meng, 2020), Colombia (Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018) and Saudi Arabia (Ahmad et al., 2014). The study design of 24 studies (Gao & Meng, 2020; Kumar et al., 2020; Aggarwal et al., 2019; Ghazalgoo et al., 2018; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Shapiro et al., 2018; Aggarwal, Singla & Miglani, 2017; Umesh, 2017; Allegretti et al., 2016; Hosseini et al., 2016; Saraf et al., 2016; Zain et al., 2016; Monteiro et al., 2015; Rajput et al., 2015; Nabeel, Ahmed & Sikander, 2014; Rogers et al., 2014; Sood, Hans & Shetty, 2014; Ashraf et al., 2013; Kanaa, Whitworth & Meechan, 2012a; Kanaa, Whitworth & Meechan, 2012b; Aggarwal et al., 2011; Poorni et al., 2011) was RCTs, and the remaining 2 studies (Ahmad et al., 2014; Subbiya et al., 2011) were NRS. The age of the participants was 15–65 years. The ethical clearance and informed consent were obtained in all except 2 studies (Lokhande et al., 2019; Subbiya et al., 2011). A total of 1,824 teeth with completely formed root apex, diagnosed with symptomatic IP and anaesthetised with either articaine or lidocaine were included in the review, 1,578 mandibular teeth from 22 studies (Gao & Meng, 2020; Kumar et al., 2020; Aggarwal et al., 2019; Ghazalgoo et al., 2018; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Shapiro et al., 2018; Aggarwal, Singla & Miglani, 2017; Umesh, 2017; Allegretti et al., 2016; Zain et al., 2016; Monteiro et al., 2015; Rajput et al., 2015; Ahmad et al., 2014; Rogers et al., 2014; Sood, Hans & Shetty, 2014; Ashraf et al., 2013; Tortamano et al., 2013; Kanaa, Whitworth & Meechan, 2012b; Subbiya et al., 2011; Aggarwal et al., 2011; Poorni et al., 2011) and 246 maxillary teeth from 4 studies comprised the present meta-analysis (Hosseini et al., 2016; Saraf et al., 2016; Nabeel, Ahmed & Sikander, 2014; Kanaa, Whitworth & Meechan, 2012a) (Table 2).

A significant methodological heterogeneity was observed between the studies. This could be attributed due to the differences in the anatomic location of the teeth being anaesthetized (mandible (Gao & Meng, 2020; Kumar et al., 2020; Aggarwal et al., 2019; Ghazalgoo et al., 2018; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Shapiro et al., 2018; Aggarwal, Singla & Miglani, 2017; Umesh, 2017; Allegretti et al., 2016; Zain et al., 2016; Monteiro et al., 2015; Rajput et al., 2015; Ahmad et al., 2014; Rogers et al., 2014; Sood, Hans & Shetty, 2014; Ashraf et al., 2013; Tortamano et al., 2013; Kanaa, Whitworth & Meechan, 2012b; Subbiya et al., 2011; Aggarwal et al., 2011; Poorni et al., 2011) or maxilla (Hosseini et al., 2016; Saraf et al., 2016; Nabeel, Ahmed & Sikander, 2014; Kanaa, Whitworth & Meechan, 2012a), anterior (Saraf et al., 2016; Kanaa, Whitworth & Meechan, 2012a; Kanaa, Whitworth & Meechan, 2012b) or posterior (Gao & Meng, 2020; Kumar et al., 2020; Aggarwal et al., 2019; Ghazalgoo et al., 2018; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Shapiro et al., 2018; Aggarwal, Singla & Miglani, 2017; Umesh, 2017; Allegretti et al., 2016; Hosseini et al., 2016; Saraf et al., 2016; Zain et al., 2016; Monteiro et al., 2015; Rajput et al., 2015; Ahmad et al., 2014; Nabeel, Ahmed & Sikander, 2014; Rogers et al., 2014; Sood, Hans & Shetty, 2014; Ashraf et al., 2013; Tortamano et al., 2013; Kanaa, Whitworth & Meechan, 2012a; Kanaa, Whitworth & Meechan, 2012b; Aggarwal et al., 2011; Poorni et al., 2011), tooth type (molars Gao & Meng, 2020; Kumar et al., 2020; Aggarwal et al., 2019; Ghazalgoo et al., 2018; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Shapiro et al., 2018; Aggarwal, Singla & Miglani, 2017; Umesh, 2017; Allegretti et al., 2016; Hosseini et al., 2016; Zain et al., 2016; Monteiro et al., 2015; Rajput et al., 2015; Ahmad et al., 2014; Rogers et al., 2014; Sood, Hans & Shetty, 2014; Ashraf et al., 2013; Tortamano et al., 2013; Kanaa, Whitworth & Meechan, 2012b; Subbiya et al., 2011; Aggarwal et al., 2011; Poorni et al., 2011, premolars (Saraf et al., 2016; Nabeel, Ahmed & Sikander, 2014; Kanaa, Whitworth & Meechan, 2012a; Kanaa, Whitworth & Meechan, 2012b) or anterior teeth (Saraf et al., 2016; Kanaa, Whitworth & Meechan, 2012a; Kanaa, Whitworth & Meechan, 2012b)), volume of anaesthetic solution administered during the intervention (0.6 mL (Aggarwal et al., 2019), 0.9 mL (Gao & Meng, 2020), 1.7 mL (Shapiro et al., 2018; Rajput et al., 2015; Nabeel, Ahmed & Sikander, 2014; Rogers et al., 2014; Subbiya et al., 2011), 1.8 mL (Kumar et al., 2020; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Aggarwal, Singla & Miglani, 2017; Hosseini et al., 2016; Zain et al., 2016; Monteiro et al., 2015; Sood, Hans & Shetty, 2014; Ashraf et al., 2013; Tortamano et al., 2013; Aggarwal et al., 2011; Poorni et al., 2011), 2.0 mL (Lokhande et al., 2019; Saraf et al., 2016; Kanaa, Whitworth & Meechan, 2012a; Kanaa, Whitworth & Meechan, 2012b), 3 mL (Umesh, 2017), 3.6 mL (Allegretti et al., 2016) and 6 mL (Umesh, 2017)), concentration of epinephrine in articaine and lidocaine and delivery route of the anaesthetic solution. Interestingly, the anaesthetic solutions for mandibular teeth were delivered via IANB (Kumar et al., 2020; Ghazalgoo et al., 2018; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Aggarwal, Singla & Miglani, 2017; Umesh, 2017; Allegretti et al., 2016; Ahmad et al., 2014; Sood, Hans & Shetty, 2014; Tortamano et al., 2013; Poorni et al., 2011), BI (Hosseini et al., 2016; Zain et al., 2016; Monteiro et al., 2015; Rajput et al., 2015; Nabeel, Ahmed & Sikander, 2014; Subbiya et al., 2011; Poorni et al., 2011), supplementary BI after IANB failure (Gao & Meng, 2020; Shapiro et al., 2018; Rogers et al., 2014; Kanaa, Whitworth & Meechan, 2012b), BI combined with intraligamentary injection (Lokhande et al., 2019), supplementary intraligamentary injections after IANB failure (Aggarwal et al., 2019), standard IANB and long Bis (Ashraf et al., 2013) and IANB plus BI (Aggarwal et al., 2011) and for maxillary teeth via BI (Kanaa, Whitworth & Meechan, 2012a), anterior middle superior alveolar nerve block (AMSA) (Saraf et al., 2016) and infraorbital nerve block (IONB) (Saraf et al., 2016). In nineteen studies, both the anaesthetic solutions were administered by the same dentist. (Gao & Meng, 2020; Kumar et al., 2020; Ghazalgoo et al., 2018; Lokhande et al., 2019; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Shapiro et al., 2018; Aggarwal, Singla & Miglani, 2017; Umesh, 2017; Allegretti et al., 2016; Zain et al., 2016; Ahmad et al., 2014; Rogers et al., 2014; Sood, Hans & Shetty, 2014; Ashraf et al., 2013; Kanaa, Whitworth & Meechan, 2012a; Kanaa, Whitworth & Meechan, 2012b; Aggarwal et al., 2011; Poorni et al., 2011) (Table 2).

The outcome parameters assessed post-intervention varied across studies. The success of pulpal anaesthesia assessed by VAS on a 4-point Likert scale or on a measured scale as no/mild pain during root canal treatment (endodontic access and pulpectomy) after administration of local anaesthesia, whereas the postoperative pain was assessed by the corresponding pain score on the numerical scale (Shapiro et al., 2018; Saraf et al., 2016; Zain et al., 2016; Rogers et al., 2014; Subbiya et al., 2011). The onset of anaesthesia was assessed from the time lapse between the end of NB and the onset of symptoms of subjective anaesthesia, such as the feeling of heaviness at the site of injection and lip numbness, or by electric pulp testing, cold testing, pulp evaluation and canal preparation using a standard digital stop clock. For the mandibular region, 19 studies assessed the success rate of anaesthesia (Gao & Meng, 2020; Kumar et al., 2020; Aggarwal et al., 2019; Ghazalgoo et al., 2018; Lokhande et al., 2019; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Shapiro et al., 2018; Aggarwal, Singla & Miglani, 2017; Allegretti et al., 2016; Zain et al., 2016; Monteiro et al., 2015; Rajput et al., 2015; Ahmad et al., 2014; Rogers et al., 2014; Sood, Hans & Shetty, 2014; Ashraf et al., 2013; Kanaa, Whitworth & Meechan, 2012b; Subbiya et al., 2011; Aggarwal et al., 2011; Poorni et al., 2011), 4 studies evaluated the postoperative pain (Umesh, 2017; Zain et al., 2016; Rogers et al., 2014; Aggarwal et al., 2011) and 1 study evaluated the mean onset time of anaesthesia (Tortamano et al., 2013). For the maxillary region, the success rate of anaesthesia was reported by 3 studies (Hosseini et al., 2016; Nabeel, Ahmed & Sikander, 2014; Kanaa, Whitworth & Meechan, 2012a), 1 study (Saraf et al., 2016) reported postoperative pain and 2 studies reported (Saraf et al., 2016; Kanaa, Whitworth & Meechan, 2012a) the mean onset time of anaesthesia. The recording time after LA injection ranged from 5–30 min in all the included studies, except in one (Umesh, 2017), which did not mention the time. VAS was used to assess the outcome in all studies except that the verbal analogue scale was applied by Allegretti et al. (2016) and the study by Tortamano et al. (2013) calculated the onset of pulpal anaesthesia in minutes. Overall, post-intervention results showed improvements in the intervention groups based on the outcome parameters (Gao & Meng, 2020; Kumar et al., 2020; Ghazalgoo et al., 2018; Lokhande et al., 2019; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Shapiro et al., 2018; Aggarwal, Singla & Miglani, 2017; Umesh, 2017; Hosseini et al., 2016; Saraf et al., 2016; Zain et al., 2016; Monteiro et al., 2015; Rajput et al., 2015; Ahmad et al., 2014; Nabeel, Ahmed & Sikander, 2014; Rogers et al., 2014; Sood, Hans & Shetty, 2014; Ashraf et al., 2013; Tortamano et al., 2013; Kanaa, Whitworth & Meechan, 2012a; Kanaa, Whitworth & Meechan, 2012b; Aggarwal et al., 2011; Poorni et al., 2011).

The mandibular postoperative pain assessed by Ghazalgoo et al. (2018), Umesh (2017), Zain et al. (2016), Rogers et al. (2014) and Aggarwal et al. (2011) using Heft Parker VAS did not show a statistically significant difference between the two groups. The time point for outcome measurement and the outcomes of interest, based on the scoring criteria, were different; also, the method of delivery of the anaesthetic solution varied in each of the included studies. Thus, these were precluded from the meta-analysis, and only qualitative analysis was conducted (Table 2).

The study by Saraf et al. (2016) concluded that 4% articaine was more efficacious than 2% lidocaine, and AMSANB was more beneficial than IONB in achieving the anaesthetic effect of maxillary anterior teeth and premolars. It was a single study included for assessing the postoperative pain using the visual analogue scale and the onset time of anaesthesia for maxillary teeth and was not considered for qualitative synthesis. The onset time of anaesthesia for mandibular teeth was assessed by Tortamano et al. (2013) and concluded that 4% articaine exhibited rapid onset with the highest duration of pulpal anaesthesia in IANB. However, since this was a single study, it was not considered for quantitative synthesis (Table 2).

Assessments of the level of evidence, risk of bias, and quality

According to JBI level of evidence, 21 studies (Gao & Meng, 2020; Kumar et al., 2020; Aggarwal et al., 2019; Ghazalgoo et al., 2018; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Shapiro et al., 2018; Aggarwal, Singla & Miglani, 2017; Umesh, 2017; Allegretti et al., 2016; Hosseini et al., 2016; Zain et al., 2016; Monteiro et al., 2015; Rajput et al., 2015; Nabeel, Ahmed & Sikander, 2014; Rogers et al., 2014; Sood, Hans & Shetty, 2014; Ashraf et al., 2013; Kanaa, Whitworth & Meechan, 2012a; Kanaa, Whitworth & Meechan, 2012b; Aggarwal et al., 2011; Poorni et al., 2011) were ranked at 1c and the remaining 5 studies (Lokhande et al., 2019; Saraf et al., 2016; Ahmad et al., 2014; Tortamano et al., 2013; Subbiya et al., 2011) as 1d.

The quality assessment of 11 RCTs was executed according to the Cochrane Risk of Bias Tool (Gao & Meng, 2020; Kumar et al., 2020; Aggarwal et al., 2019; Ghazalgoo et al., 2018; Lokhande et al., 2019; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Shapiro et al., 2018; Aggarwal, Singla & Miglani, 2017; Umesh, 2017; Allegretti et al., 2016; Hosseini et al., 2016; Saraf et al., 2016; Monteiro et al., 2015; Rajput et al., 2015; Nabeel, Ahmed & Sikander, 2014; Rogers et al., 2014; Sood, Hans & Shetty, 2014; Ashraf et al., 2013; Tortamano et al., 2013; Kanaa, Whitworth & Meechan, 2012a; Kanaa, Whitworth & Meechan, 2012b; Aggarwal et al., 2011; Poorni et al., 2011). Moreover, 13 studies (Gao & Meng, 2020; Aggarwal et al., 2019; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Shapiro et al., 2018; Aggarwal, Singla & Miglani, 2017; Umesh, 2017; Allegretti et al., 2016; Hosseini et al., 2016; Monteiro et al., 2015; Rogers et al., 2014; Ashraf et al., 2013; Kanaa, Whitworth & Meechan, 2012a; Aggarwal et al., 2011; Poorni et al., 2011) showed a low potential risk of bias, 3 (Kumar et al., 2020; Monteiro et al., 2015; Sood, Hans & Shetty, 2014) presented a moderate risk and 7 (Lokhande et al., 2019; Saraf et al., 2016; Zain et al., 2016; Rajput et al., 2015; Nabeel, Ahmed & Sikander, 2014; Tortamano et al., 2013; Kanaa, Whitworth & Meechan, 2012b) had a high potential risk of bias (Fig. 2).

MINORS was used for quality assessment of 2 non-randomised comparative studies (Ahmad et al., 2014; Subbiya et al., 2011) that presented a score of 21 (Table 3). Only 5/26 studies (Hosseini et al., 2016; Ahmad et al., 2014; Rogers et al., 2014; Ashraf et al., 2013; Poorni et al., 2011) disclosed receiving financial support for the work.

Synthesis of results

A total of 22 studies (Gao & Meng, 2020; Kumar et al., 2020; Aggarwal et al., 2019; Lokhande et al., 2019; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Shapiro et al., 2018; Aggarwal, Singla & Miglani, 2017; Allegretti et al., 2016; Hosseini et al., 2016; Zain et al., 2016; Monteiro et al., 2015; Rajput et al., 2015; Ahmad et al., 2014; Nabeel, Ahmed & Sikander, 2014; Rogers et al., 2014; Sood, Hans & Shetty, 2014; Ashraf et al., 2013; Tortamano et al., 2013; Kanaa, Whitworth & Meechan, 2012a; Kanaa, Whitworth & Meechan, 2012b; Subbiya et al., 2011; Aggarwal et al., 2011; Poorni et al., 2011) fulfilled the inclusion criteria for quantitative analysis. Subsequently, two meta-analyses, including one subgroup analysis, were performed on the success rate of anaesthesia for mandibular and maxillary teeth.

The success rate of anaesthesia for mandibular teeth

The pooled outcomes from 19 studies, in tooth level unit, using random-effect model showed that 4% articaine resulted in a success rate 1.37-fold higher than that of 2% lidocaine (RR, 1.37; 95% CI [1.17–1.62]; P = 0.0002), showing statistically significant difference favouring the articaine group and 72% heterogeneity (I²). When subgroup analysis was performed according to the injection techniques using random-effect model, it was observed that for IANB (Kumar et al., 2020; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Aggarwal, Singla & Miglani, 2017; Allegretti et al., 2016; Ahmad et al., 2014; Sood, Hans & Shetty, 2014; Poorni et al., 2011), 4% articaine resulted in a success rate 1.25-fold higher than that for 2% lidocaine (RR, 1.25; 95% CI [0.98–1.59]; P = 0.007) showing statistically significant difference favouring the articaine group with 43% heterogeneity. For BI technique (Kumar et al., 2020; Zain et al., 2016; Monteiro et al., 2015; Rajput et al., 2015; Kanaa, Whitworth & Meechan, 2012b; Poorni et al., 2011), 4% articaine resulted in a success rate 1.13-fold higher than that for 2% lidocaine (RR, 1.13; 95% CI [0.89–1.45]; P = 0.31) with 68% heterogeneity. Supplementary BI after IANB failure technique (Gao & Meng, 2020; Shapiro et al., 2018; Rogers et al., 2014; Kanaa, Whitworth & Meechan, 2012b) showed that 4% articaine resulted in a success rate of 1.53-fold higher than 2% lidocaine (RR, 1.53; 95% CI [1.821–1.94]; P = 0.0004) showing statistically significant difference favouring the articaine group with the heterogeneity of 36% (I²). BI combined with intraligamentary injection technique (Lokhande et al., 2019) showed that 4% articaine resulted in a success rate of 8.33-fold higher than that for 2% lidocaine (RR, 8.33; 95% CI [2.81–24.67]; P = 0.0001) showing statistically significant difference favouring the articaine group. For supplementary intraligamentary injections after IANB failure (Aggarwal et al., 2019) and standard IANB and long BI technique (Ashraf et al., 2013), 4% articaine resulted in a success rate 0.9-fold (RR, 0.9; 95% CI [0.67–1.2]; P = 0.47) and 2.41-fold (RR, 2.41; 95% CI [1.56–1.2]; P < 0.0001) higher than that of 2% lidocaine, respectively showing statistically significant difference favouring the articaine group for standard IANB and long BI technique but not for supplementary intraligamentary injections after IANB failure. For IANB plus BI technique (Aggarwal et al., 2011), 4% articaine resulted in a success rate of 1.38-fold higher than that for 2% lidocaine (RR, 1.38; 95% CI [0.74–2.6]; P < 0.0001) showing a statistically significant difference favouring the articaine group (Fig. 3).

The success rate of anaesthesia for maxillary teeth

The pooled outcomes from 3 studies (Hosseini et al., 2016; Nabeel, Ahmed & Sikander, 2014; Kanaa, Whitworth & Meechan, 2012a) on tooth level unit for maxillary buccal infiltration technique showed that 4% articaine resulted in a success rate of 1.06-fold higher than that for 2% lidocaine (RR, 1.06; 95% CI [0.95–1.2]; P = 0.3, I² = 0%) using random-effects model, showing statistically insignificant difference (Fig. 4).

Sensitivity analysis

Table 4 represents the results of sensitivity analysis for mandibular teeth. Studies of high risk (Lokhande et al., 2019; Saraf et al., 2016; Zain et al., 2016; Rajput et al., 2015; Nabeel, Ahmed & Sikander, 2014; Tortamano et al., 2013; Kanaa, Whitworth & Meechan, 2012b), moderate risk (Kumar et al., 2020; Monteiro et al., 2015; Sood, Hans & Shetty, 2014) or low risk of bias (Gao & Meng, 2020; Kumar et al., 2020; Aggarwal et al., 2019; Ghazalgoo et al., 2018; Lokhande et al., 2019; Martínez-Martínez, Freyle-Granados & Senior-Carmona, 2018; Shapiro et al., 2018; Aggarwal, Singla & Miglani, 2017; Umesh, 2017; Allegretti et al., 2016; Hosseini et al., 2016; Saraf et al., 2016; Monteiro et al., 2015; Rajput et al., 2015; Ahmad et al., 2014; Nabeel, Ahmed & Sikander, 2014; Rogers et al., 2014; Sood, Hans & Shetty, 2014; Ashraf et al., 2013; Tortamano et al., 2013; Kanaa, Whitworth & Meechan, 2012a; Kanaa, Whitworth & Meechan, 2012b; Aggarwal et al., 2011; Poorni et al., 2011) were excluded from sensitivity analysis. The clinical success rates comparing the articaine and lidocaine groups showed a significant change after the exclusion of these studies. Reanalysis using the fixed-effect model also showed that the outcomes were not adverse. The exclusion of subgroups with a single study showed a significant improvement in the success rate of articaine group as compared to the lidocaine group in the treatment of IP. Moreover, the subgroup analysis for different injection techniques showed a significant change after the inclusion of only supplementary BI after IANB failure technique as compared to the inclusion of IANB and BI technique (Table 4).

Publication bias for studies included on mandibular anaesthetic technique was evaluated using a funnel plot (Fig. 5). The funnel plot showed asymmetry at the apex from the centre line having more studies on the right side as compared to left, representing a lack of inclusion of publications describing non-significant intervention results as well as the omission of unpublished studies that might result in an over-estimation of the true effect of an intervention.

KEY HIGHLIGHTS of the current analysis

1. Successful pulpal anaesthesia is the cornerstone for painless root canal treatment, especially in patients with symptomatic pulpitis.

2. Articaine was introduced to overcome supplemental anaesthesia and to increase the effectiveness of the quality of anaesthesia.

3. Articaine is associated with a lower visual analogue scale rating for pain.

4. Articaine resulted in 1.37-fold and 1.06-fold higher clinical success rate than lidocaine for mandibular and maxillary teeth respectively.