doi:10.1111/iej.

13215

REVIEW
Is articaine more effective than lidocaine in
patients with irreversible pulpitis? An umbrella
review

V. Nagendrababu1 , H. F. Duncan2 , J. Whitworth3, M. H. Nekoofar4,5 ,

S. J. Pulikkotil1 , S. K. Veettil6 & P. M. H. Dummer5
1
Division of Clinical Dentistry, School of Dentistry, International Medical University, Kuala Lumpur, Malaysia; 2Division of
Restorative Dentistry, Dublin Dental University Hospital, Trinity College Dublin, Dublin, Ireland; 3Centre for Oral Health
Research, School of Dental Sciences, Newcastle University, Newcastle upon Tyne, UK; 4Department of Endodontics, School of
Dentistry, Tehran University of Medical Sciences, Tehran, Iran; 5School of Dentistry, College of Biomedical and Life Sciences,
Cardiff University, Cardiff, UK; and 6School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia

Abstract independent reviewers using the AMSTAR tool (a

measurement tool to assess systematic reviews). Each
Nagendrababu V, Duncan HF, Whitworth J,
of the 11 AMSTAR items was given a score of 1 if
Nekoofar MH, Pulikkotil SJ, Veettil SK, Dummer
the specific criterion was met, or 0 if the criterion
PMH. Is articaine more effective than lidocaine in patients
was not met or the information was unclear.
with irreversible pulpitis? An umbrella review. International
Results Five systematic reviews with meta-analyses
Endodontic Journal, 53, 200–213, 2020.
were included. The AMSTAR score for the reviews ran-
Background Pain management can be challenging ged from 8 to 11, out of a maximum score of 11, and all
during root canal treatment of teeth with irreversible reviews were categorized as ‘high’ quality. Two reviews
pulpitis. scored 0 for item 8 in AMSTAR because the scientific
Aim To identify whether articaine or lidocaine is the quality of the clinical trials included in these reviews
most appropriate local anaesthetic solution for teeth with was not used in the formulation of the conclusions.
irreversible pulpitis undergoing root canal treatment. Limitations Systematic reviews published only in
Data source The protocol of this umbrella review the English language were included. Only a small num-
is registered in the PROSPERO database ber of studies were available to assess pain intensity
(CRD42019137624). PubMed, EBSCHO host and Sco- during the injection phase, the time until the onset of
pus databases were searched until June 2019. anaesthesia and the occurrence of adverse events.
Study eligibility criteria, participants and Conclusions and implications of key find-
interventions Systematic reviews published in English ings Articaine is more effective than lidocaine for
comparing the effectiveness of local anaesthesia following local anaesthesia of teeth with irreversible pulpitis
administration of articaine or lidocaine in patients under- undergoing root canal treatment. There is limited evi-
going root canal treatment of teeth diagnosed with irre- dence that injection of articaine is less painful, has
versible pulpitis were included. Two independent reviewers more rapid onset and has fewer adverse events com-
selected the studies and carried out the data extraction and pared with lidocaine.
the appraisal of the included reviews. Disagreements were
Keywords: articaine, irreversible pulpitis, lidocaine,
resolved in consultation with a third reviewer.
meta-analysis, umbrella review, systematic review.
Study appraisal and synthesis methods The
quality of the included reviews was appraised by two Received 2 September 2019; accepted 2 September 2019

Correspondence: V. Nagendrababu, Division of Clinical Dentistry, School of Dentistry, International Medical University, Bukit
Jalil – 57000, Kuala Lumpur, Malaysia (e-mail: [email protected]).

200 International Endodontic Journal, 53, 200–213, 2020 © 2019 International Endodontic Journal. Published by John Wiley & Sons Ltd
 13652591, 2020, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13215 by Cochrane Mexico, Wiley Online Library on [12/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Nagendrababu et al. Anaesthetic efficacy of articaine and lidocaine

In an attempt to better understand the inconsistent

Introduction
results of these randomized clinical trials, several sys-
Adequate pain management is essential to ensure tematic reviews and meta-analyses comparing the effi-
patient comfort and reduce fear and anxiety during cacy of articaine and lidocaine have been published.
dental treatment (Scott & Hirschman 1982, Khan The first systematic review comparing articaine with
et al. 2016). Achieving profound anaesthesia during lidocaine (Katyal 2010) concluded that articaine was
root canal treatment is often challenging, particularly more effective than lidocaine for successful local
in teeth with symptomatic irreversible pulpitis (Mod- anaesthesia during routine dentistry following infiltra-
aresi et al. 2006, Segura-Egea et al. 2009). This may tion in the first maxillary molar region and after
be attributed to a range of factors, including central IANB in the mandibular molar region. However, this
sensitization, prostaglandin-induced sensitization of systematic review included teeth with a range of pul-
peripheral nociceptors, acute tachyphylaxis, inflam- pal diagnoses and did not select specifically for irre-
matory responses affecting local tissue pH and blood versible pulpitis. Another review (Brandt et al. 2011)
flow, and psychological factors (Hargreaves & Keiser compared the anaesthetic efficacy of lidocaine with
2004, Henry & Hargreaves 2007, Khan et al. 2007, articaine for pulpal anaesthesia in maxillary and
Owatz et al. 2007). mandibular posterior teeth, after infiltration or block
Lidocaine (or lignocaine) is the most commonly used routes of administration, respectively. It concluded
local anaesthetic solution in dentistry (Gaffen & Haas that whilst there was no difference in efficacy between
2009, Oliver et al. 2016). Chemically classed as an articaine and lidocaine, it was too early to recom-
amide anaesthetic, lidocaine has a rapid onset of action mend articaine for mandibular block anaesthesia for
and an intermediate duration of anaesthesia when com- teeth with irreversible pulpitis (Brandt et al. 2011).
bined with adrenaline. It is generally accepted that this Since then, four additional systematic reviews have
combination has the ability to produce pulpal anaesthe- concluded that articaine is superior to lidocaine for
sia for approximately 60 min and soft tissue anaesthesia pulpal anaesthesia, at least by some routes of admin-
for 3–5 h (Malamed 2006, Kung et al. 2015). Articaine istration, for teeth with irreversible pulpitis (Kung
is another amide local anaesthetic solution that substi- et al. 2015, Su et al. 2016, St George et al. 2018,
tutes a thiophene ring for the benzene ring present in Nagendrababu et al. 2019). The review by Kung et al.
lidocaine. This modification allows articaine molecules (2015) analysed studies on infiltration and block
to diffuse through nerve membranes more effectively anaesthetic techniques separately and concluded that
than lidocaine molecules, due to increased lipid solubil- there was no difference in the efficacy of articaine
ity. The two solutions further differ by the incorporation and lidocaine for mandibular block or maxillary infil-
of an ester linkage into the articaine molecule, which tration, with the only benefit of articaine being for
results in hydrolysis of articaine by plasma esterases supplementary infiltrations in mandibular teeth. The
(Malamed et al. 2001). Ninety to 95% of articaine is more recent reviews reported that articaine was supe-
metabolized in the blood by plasma esterases, with the rior to lidocaine for pulpal anaesthesia following
remainder being broken down in the liver, whereas 90% IANB during treatment of mandibular posterior teeth
of lidocaine is metabolized in the liver (Oertel et al. with irreversible pulpitis in both children (Su et al.
1997, Brandt et al. 2011). 2016) and adults (Nagendrababu et al. 2019),
Several randomized clinical trials have reported whereas the review by St George et al. (2018)
that articaine is more effective than lidocaine in reported that there was no evidence of a difference
achieving profound dental pulp anaesthesia particu- between the anaesthetic solutions.
larly following infiltration in the maxilla (Evans et al. An ‘umbrella’ review represents an overview of sys-
2008, Srinivasan et al. 2009) and as a supplementary tematic reviews and is a new approach to analyse a
infiltration following inferior alveolar nerve block collection of systematic reviews on a defined topic or
(IANB) in the mandible (Aggarwal et al. 2009, Ashraf question. An umbrella review should identify both the
et al. 2013, Rogers et al. 2014). Conversely, other strengths and shortcomings of existing systematic
clinical trials have reported no benefit of articaine reviews that could affect the quality of the results
over lidocaine for pulpal anaesthesia in irreversibly obtained. Such reviews also help to identify consistent
pulpitic mandibular teeth after IANB (Tortamano or contradictory findings when considering whether
et al. 2009, Aggarwal et al. 2017). the independent systematic reviews assessed the

© 2019 International Endodontic Journal. Published by John Wiley & Sons Ltd International Endodontic Journal, 53, 200–213, 2020 201
 13652591, 2020, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13215 by Cochrane Mexico, Wiley Online Library on [12/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Anaesthetic efficacy of articaine and lidocaine Nagendrababu et al.

question and arrived at reliable conclusions (Aro-

Selection criteria
mataris et al. 2015, 2017).
This umbrella review was undertaken to analyse Articles were included if they satisfied the following
the results of previous systematic reviews in order to criteria:
determine: • systematic reviews with or without meta-analysis;
1. the most effective local anaesthetic solution for • published in English;
teeth with irreversible pulpitis when comparing • reviews comparing anaesthetic efficacy between
articaine and lidocaine; articaine and lidocaine/lignocaine in patients
2. the anaesthetic solution associated with the least undergoing root canal treatment in maxillary and/
pain during injection when comparing articaine or mandibular teeth with irreversible pulpitis.
and lidocaine; Narrative reviews, case reports and individual clini-
3. the anaesthetic solution with the most rapid cal trials were excluded.
onset of pulpal anaesthesia when comparing arti-
caine and lidocaine;
Data source and search strategy
4. the anaesthetic solution with the fewest adverse
events when comparing articaine and lidocaine; The literature search was performed in PubMed, EBS-
and COhost and Scopus electronic databases from incep-
5. reporting deficiencies and gaps in knowledge in tion to June 2019 using the following search
this area. strategy: (((((articaine) OR lidocaine) OR lignocaine))
AND ((((((((root canal) OR endod) OR irreversible pul-
pitis) OR IANB) OR Gow-Gates) OR mental incisive
Methods
nerve block) OR Vazirani-Akinosi) OR maxillary infil-
This current umbrella review was developed accord- tration)) AND ((systematic review) OR meta-analysis).
ing to the Preferred Reporting Items for Systematic Reference lists of included systematic reviews were
Reviews and Meta-Analyses (PRISMA) guidelines also hand-searched to identify other relevant system-
(Moher et al. 2009). The protocol of the review was atic reviews. Initially, two independent reviewers (VN,
registered in the PROSPERO database SP) screened the titles and abstracts of identified
(CRD42019137624). reviews to decide on inclusion or exclusion. In cases
of doubt after reading the title and abstract, the full
text of each systematic review was read to decide on
Review questions
their inclusion/exclusion. Disagreements were
The review questions were developed based on the resolved with the help of a third reviewer (PD). If
PICO (population, intervention, control and outcome) needed, the authors of included reviews were con-
framework: tacted to provide missing data and/or clarify informa-
1. Is articaine (I) more effective than lidocaine (C) tion that was unclear.
for dental pulp anaesthesia (O) in maxillary and
mandibular teeth with irreversible pulpitis under- Data extraction
going root canal treatment (P)?
2. Does articaine (I) result in more rapid onset of Two independent reviewers (NV, SP) performed the
pulpal anaesthesia (O) than lidocaine (C) in max- data extraction. Disagreements were resolved by con-
illary and mandibular teeth with irreversible pul- sulting with the third reviewer (PD). Two separate
pitis undergoing root canal treatment (P)? data extraction forms were created:
3. Does the injection of articaine (I) cause less pain 1. General characteristics of the included systematic
(O) than the injection of lidocaine (C) in patients reviews and meta-analyses: name and country of
(P) with irreversibly pulpitic maxillary and the first author, year of publication, name of the
mandibular teeth undergoing root canal treat- journal published, database searched, search
ment? period during which the original included stud-
4. Does articaine (I) result in fewer adverse events (O) ies were published, languages included, interven-
than lidocaine (C) following administration for tions, number of studies included for meta-
patients undergoing root canal treatment of maxil- analysis, number of participants, type of study
lary or mandibular teeth with irreversible pulpitis? design included, instrument used to assess

202 International Endodontic Journal, 53, 200–213, 2020 © 2019 International Endodontic Journal. Published by John Wiley & Sons Ltd
 13652591, 2020, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13215 by Cochrane Mexico, Wiley Online Library on [12/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Nagendrababu et al. Anaesthetic efficacy of articaine and lidocaine

the quality of included studies and outcome

Results
assessed;
2. Summary of the meta-analyses: meta-analysis
Literature search
model, number of samples in intervention and
comparison group (total and events), study-speci- Relevant systematic reviews were identified and
fic relative risk estimates (risk ratio, odds ratio or selected (Fig. 1). The initial search resulted in 863
standardized mean differences) along with the reviews, and of these, 107 were removed as they
corresponding 95% confidence intervals (CI), I2 were duplicates. Following title and abstract screen-
statistic and publication bias. ing, a total of 748 studies were excluded, because
they did not satisfy the inclusion criteria with eight
studies being shortlisted for full-text retrieval. After
Primary outcome
reading the full text, three reviews were excluded for
Successful pulpal anaesthesia in maxillary and the following reasons: inclusion of studies with other
mandibular teeth with irreversible pulpitis undergoing anaesthetic solutions in the meta-analysis (Tupyota
root canal treatment. The diagnostic criteria for irre- et al. 2018), inclusion of studies with a range of pul-
versible pulpitis were moderate-to-severe spontaneous pal diagnoses and not limited to irreversible pulpitis
pain, prolonged response to a cold test and a positive (Katyal 2010, Bartlett & Mansoor 2016). Finally, five
response to an electric pulp test. Anaesthetic success systematic reviews with meta-analysis were included
was defined as: no pain or mild pain according to for the current umbrella review (Brandt et al. 2011,
patient-reported pain scores during access cavity Kung et al. 2015, Su et al. 2016, St George et al.
preparation and instrumentation or no response to 2018, Nagendrababu et al. 2019).
pulp sensibility testing (heat/cold/electric pulp tester).

Characteristics of the included systematic reviews

Secondary outcomes
The general characteristics of the included systematic
(i) Pain intensity during local anaesthetic injection, reviews with meta-analysis are summarized in
(ii) Time of onset of pulpal anaesthesia, and (iii) Table 1. Figure 2 provides a summary of the meta-
Adverse events reported. analyses for pulpal anaesthesia and adverse events,
whereas Fig. 3 provides the summary of the meta-
analyses for pain intensity during injection and onset
Methodological quality assessment
time of pulpal anaesthesia. Amongst the five included
Two independent reviewers (VN, SP) appraised the reviews, two were from the USA, with one each from
methodological quality of included systematic reviews the UK, China and Malaysia. The number of data-
using the AMSTAR tool (a measurement tool to bases searched by the authors of the included reviews
assess systematic reviews; Shea et al. 2007). A third ranged from two to five, and the reviews included
reviewer (PD) resolved doubts or discrepancies between 3 and 15 randomized clinical trials. No other
between the two reviewers. The AMSTAR checklist type of experimental clinical study was included in
consists of 11 items. Each item was given a score of 1 any review. Su et al. (2016) included amongst the 15
if the specific criterion was met, or 0 if the criterion individual randomized clinical trials they analysed,
was not met or information was unclear. Missing four that included children under 16 years of age; all
information was obtained by contacting the authors; other reviews included only adults (>16 years).
if there was no response, the item was scored as 0. Three of the reviews used the Cochrane Collabora-
After scoring, each systematic review was categorized tion ‘Risk of Bias’ tool for quality assessment (Kung
into high, medium and low quality, if it received a et al. 2015, Su et al. 2016, St George et al. 2018),
score between 8 and 11, 4–7 and 0–3, respectively whereas one review used the more recently intro-
(Rangel-Rinc on et al. 2018). The degree of agreement duced Cochrane risk of bias tool (RoB 2.0; Nagen-
between the two independent reviewers (VN and SP) drababu et al. 2019). Brandt et al. (2011) assessed
and intra-examiner agreement in assessing the the methodological quality of the trials they included
methodological quality of included systematic reviews within five domains, namely randomization, alloca-
was calculated by Cohen’s kappa analysis. tion concealment, outcome assessment, adverse

© 2019 International Endodontic Journal. Published by John Wiley & Sons Ltd International Endodontic Journal, 53, 200–213, 2020 203
 13652591, 2020, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13215 by Cochrane Mexico, Wiley Online Library on [12/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Anaesthetic efficacy of articaine and lidocaine Nagendrababu et al.

Identification
Records identified through database Additional records identified
searching through other sources
(n = 863) (n = 0)

Records after duplicates removed

(n = 756)

Screening Records screened Records excluded

(n = 756) (n = 748)
Eligibility

Full-text articles assessed Full-text articles excluded,

for eligibility with reasons
(n = 8) (n = 3)

Studies included in
Included

qualitative synthesis
(n = 5)

Figure 1 Search process.

events reporting and loss to follow-up, as indicators of et al. 2015, Su et al. 2016) comparing the anaesthetic
quality. All the systematic reviews were published in efficacy of articaine with lidocaine including all delivery
SCImago tier1/tier2 journals such as International routes (combined with infiltration, mandibular blocks,
Endodontic Journal (Nagendrababu et al. 2019), Journal supplemental infiltration), there was moderate hetero-
of Endodontics (Kung et al. 2015), Australian Endodon- geneity (30–60% [Higgins & Green 2011]), whereas in
tic Journal (Su et al. 2016) and Journal of the American the review by Brandt et al. (2011) 0% heterogeneity
Dental Association (Brandt et al. 2011). One review was observed.
was published in the Cochrane database (St George
et al. 2018).
Methodological quality
Heterogeneity and publication bias in the included
A quality assessment of the five systematic reviews
systematic reviews
with meta-analysis included in this umbrella review is
Each systematic review used funnel plots to detect pub- provided in Table S1. The AMSTAR score for the
lication bias. The plots in two of the reviews were sym- included systematic reviews ranged from 8 to 11.
metrical and revealed no evidence of bias (Su et al. Two reviews (Brandt et al. 2011, Kung et al. 2015)
2016, Nagendrababu et al. 2019), whereas the review were scored as 0 for ‘scientific quality of the included
by Kung et al. (2015) revealed asymmetry in the base studies used appropriately in formulating conclu-
of the funnel, indicative of potential publication bias. In sions’. All the systematic reviews were categorized as
the review by Brandt et al. (2011), publication bias ‘high’ quality. The intra- and interexaminer reliability
was not assessed, with no reason being provided, whilst scores (VK and SP) for scoring the AMSTAR items of
in the review by St George et al. (2018), publication the included studies based on the Kappa statistics
bias was not assessed due to the small number of trials were 1 and 0.88 (P < 0.001), respectively. This
selected. In the meta-analyses of two studies (Kung equates to ‘almost perfect’ agreement.

204 International Endodontic Journal, 53, 200–213, 2020 © 2019 International Endodontic Journal. Published by John Wiley & Sons Ltd
 Table 1 Main characteristics of the included systematic reviews and meta-analysis

Number
of
Country studies Study
Name of the of the included design –
S journal first Search for meta- included Instrument of quality
No Author, year published Database searched author period Language Groups analysis studies assessment

1 Brandt et al. Journal of MEDLINE and Embase USA 1970– English, German, 4% Articaine, 3 Randomized Five domains
(2011) American 2009 Croatian and 2% Lidocaine clinical namely
Dental Russian in combination trials randomization,
Association with allocation
vasoconstrictor concealment,
outcome
assessment,
adverse effect
reporting and loss
to follow-up
2. Kung et al. Journal of MEDLINE, Scopus and USA 1976– No language 4% Articaine, 10 Randomized Cochrane
(2015) Endodontics Cochrane Library 2013 restriction. (if an 2% Lidocaine clinical Collaboration
abstract was not in combination trials
available in with

© 2019 International Endodontic Journal. Published by John Wiley & Sons Ltd
English for vasoconstrictor
screening
purposes, the
article was not
included)
3 Su et al. (2016) Australian MEDLINE, Cochrane China 1946– No language 4% Articaine, 15 Randomized Cochrane
Endodontic Central Register of 2015 restriction 2% Lidocaine clinical Collaboration ‘Risk
Journal Controlled Trials, in combination trials of Bias’ tool
EMBASE, Chinese with
BioMedical Literature vasoconstrictor
Database and China
National
Knowledge Infrastructure
4 St George Cochrane Cochrane Central UK Until No language 4% Articaine, 4 Randomized Cochrane
et al. (2018) Database of Register of Controlled 2018 restriction 2% Lidocaine clinical Collaboration ‘Risk
Systematic Trials (CENTRAL; the in combination trials of Bias’ tool
Reviews Cochrane Library; 2018, with
Issue 1), MEDLINE vasoconstrictor
(OVID SP), Embase,
CINAHL PLUS, WEB OF
SCIENCE

International Endodontic Journal, 53, 200–213, 2020

Nagendrababu et al. Anaesthetic efficacy of articaine and lidocaine

205
13652591, 2020, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13215 by Cochrane Mexico, Wiley Online Library on [12/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
 13652591, 2020, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13215 by Cochrane Mexico, Wiley Online Library on [12/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Anaesthetic efficacy of articaine and lidocaine Nagendrababu et al.

Instrument of quality

Cochrane risk of bias

Principal findings

assessment
Five systematic reviews were finally included in this
review, which contained 35 individual meta-analyses

(RoB 2.0)
addressing four unique outcomes:
1. Pulpal anaesthesia success rate from 31 meta-
analyses;

Randomized
2. Pain intensity during injection from 1 meta-anal-
included
design –

studies
Study

ysis;

clinical
trials
3. Onset time of pulpal anaesthesia from 1 meta-
analyses;
4. Adverse events from 1 meta-analysis.
for meta-
included
Number

analysis
studies
of

15

Pulpal anaesthesia
Three reviews reported that articaine had a 1.15–2.3
vasoconstrictor
in combination
2% Lidocaine

times greater success rate than lidocaine (Kung et al.

4% Articaine,
Groups

2015, Su et al. 2016, St George et al. 2018), whereas

Brandt et al. (2011) concluded there was no differ-
with

ence between the solutions. Nagendrababu et al.

(2019) included eight clinical trials in their meta-
analysis and concluded that articaine had a 1.16
Language

times higher anaesthetic success rate than lidocaine,

when the solutions were delivered as an IANB.
English

Tooth and jaw. Generally, infiltrations are the preferred

local anaesthetic technique for maxillary teeth with
Inception

irreversible pulpitis. Three of the five reviews (Kung

Search

to 2018
period

et al. 2015, Su et al. 2016, St George et al. 2018)

performed a separate analysis for maxillary teeth.
Amongst these, two reviews (Su et al. 2016, St
Malaysia
Country

author
of the
first

George et al. 2018) concluded that articaine had a

superior success rate than lidocaine, whereas another
(Kung et al. 2015) concluded there was no difference
between the two anaesthetic solutions for maxillary
Database searched

teeth. Four of the reviews performed analyses sepa-

PubMed, Scopus

rately for mandibular teeth with irreversible pulpitis.

They concluded that articaine had a greater anaes-
thetic success rate compared with lidocaine when the
anaesthetic solution was delivered by any technique
for anaesthetizing mandibular molars.
Name of the

International
Endodontic
published

Technique. Three reviews (Kung et al. 2015, Su et al.

journal

Journal

2016, St George et al. 2018) combined studies assess-

ing the effectiveness of anaesthesia using various
techniques of conventional IANB alone and conven-
Nagendrababu

tional IANB supplemented by buccal infiltration. The

Author, year
Table 1 Continued

et al. (2019)

other two reviews (Su et al. 2016, Nagendrababu

et al. 2019) evaluated studies that used only IANBs.
The analysis in these reviews revealed that articaine
was superior to lidocaine for mandibular molars with
No

irreversible pulpitis undergoing root canal treatment.

S

206 International Endodontic Journal, 53, 200–213, 2020 © 2019 International Endodontic Journal. Published by John Wiley & Sons Ltd
 13652591, 2020, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13215 by Cochrane Mexico, Wiley Online Library on [12/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Nagendrababu et al. Anaesthetic efficacy of articaine and lidocaine

Overall, four of the reviews concluded that articaine for clinical decision-making (Silva et al. 2012, 2015).
had a greater anaesthetic success rate than lidocaine Therefore, an umbrella review approach was used in
during the treatment of teeth with irreversible pulpitis. this study to provide clear and unambiguous recom-
mendations to clinicians when selecting articaine or
Pain during injection lidocaine anaesthetic solutions for local anaesthesia of
Su et al. (2016) reported that articaine was associated their adult patients presenting with irreversible pulpi-
with a lower pain (VAS) score during injection than tis and requiring root canal treatment. The authors of
lidocaine; however, these data were taken from only the current umbrella review had planned to perform
one clinical trial (Kanaa et al. 2012). a meta-analysis, if the primary outcome of the five
included reviews revealed a disagreement. However,
Onset of anaesthesia the more recent systematic reviews (Kung et al.
Su et al. (2016), taking into account the outcome of 2015, Su et al. 2016, St George et al. 2018, Nagen-
a meta-analyses from four pooled clinical trials, drababu et al. 2019) all concluded that articaine was
reported that articaine was associated with a more more effective than lidocaine, whereas Brandt et al.
rapid onset of pulpal anaesthesia than lidocaine. (2011) reported no difference, probably due to the
small number of clinical trials included. As a conse-
Adverse events quence of the consistent conclusions, it was consid-
Kung et al. (2015) highlighted that one trial reported ered that there was no need for a meta-analysis.
the absence of adverse events, whereas no mention
was made in the other studies they included. In con-
Quality of systematic reviews
trast, Su et al. (2016) performed a meta-analysis for
adverse events and reported that articaine was associ- The quality of the individual systematic reviews
ated with a lower percentage of patients suffering included in this umbrella review was categorized as
adverse events than lidocaine, including oedema, hae- ‘high’ when using the AMSTAR tool. AMSTAR has
matoma, dizziness, nausea, allergy and shock. Thus, been reported to provide good evidence of validity and
they concluded that articaine is less toxic and safer to reliability, and helps the reader to appraise the critical
use than to lidocaine (Su et al. 2016). None of the components that a systematic review should include
systematic reviews mentioned paraesthesia as an in order to appropriately interpret the results and its
adverse event; however, this may not have been pos- implications (Shea et al. 2007). AMSTAR has 11
sible to identify and report since there was no long- domains namely priori design, study selection and
term follow-up of patients. data extraction process, literature search, status of
publication, studies list, characteristics of included
studies, scientific quality of the included studies
Discussion
assessed and documented, scientific quality of the
The inability to achieve pulpal anaesthesia during included studies used appropriately in formulating
root canal treatment has the potential to increase fear conclusions, methods to combine findings, publication
and anxiety in patients and thus make patient man- bias and conflict of interest (Shea et al. 2007). A high
agement more challenging, prolong the duration of AMSTAR score for a systematic review does not nec-
appointments and create concerns in the mind of essarily mean that the original randomized clinical
patients about the competence of the clinician. It may trials they included were of high quality. However,
also exacerbate systemic medical conditions (Kung carrying out a quality assessment of the individual
et al. 2015). In an umbrella review, the results of randomized clinical trials included in a systematic
multiple systematic reviews are compiled into a single review is important in order to evaluate the quality of
overarching review, before synthesizing the data in evidence obtained by a subsequent meta-analysis.
an attempt to integrate all relevant information. The Two of the systematic reviews failed to formulate their
intention is to create greater clarity, reduce uncer- conclusions based on the quality of the randomized
tainty for decision-making, identify residual gaps in trials they included (Brandt et al. 2011, Kung et al.
knowledge and provide a reference publication that 2015). This is a critical flaw of these reviews as it will
contains the essential information on that topic. An affect the results and conclusions, which may be used
umbrella review is considered to provide the highest subsequently to develop clinical practice guidelines
level of scientific evidence and thus the benchmark that directly influence patient care.

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Anaesthetic efficacy of articaine and lidocaine Nagendrababu et al.

Figure 2 Meta-analyses summary for pulpal anaesthesia and adverse events outcomes. CI, confidence interval; MD, mean dif-
ference; NR, not reported; NA, not applicable; RR, risk ratio; OR, odds ratio.

Figure 3 Meta-analyses summary for pain intensity during injection and onset time of pulpal anaesthesia. CI, confidence inter-
val; MD, mean difference; NR, not reported; NA, not applicable; RR, risk ratio; OR, odds ratio.

the PROSPERO database improves the methodological

Strengths
and reporting quality of a review, promoting trans-
The current umbrella review was conducted with a parency and reducing potential for bias, and helping
robust methodology as it used three electronic data- to avoid unintended duplication of reviews.
bases to search for and identify suitable systematic
reviews and two independent reviewers were involved
Limitations
in systematic review selection and data extraction.
This rigorous methodology improves the quality of The heterogeneity amongst the randomized clinical
the review process. The umbrella review only trials included within each systematic review is by
included systematic reviews that contained random- extension also a limitation of this umbrella review.
ized clinical trials, to provide the highest level of evi- Study heterogeneity included factors such as geo-
dence. Furthermore, a priori protocol registration in graphic location, sample size, experience of operators,

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Nagendrababu et al. Anaesthetic efficacy of articaine and lidocaine

criteria for defining the diagnosis of symptomatic irre- the included systematic reviews and meta-analyses, as
versible pulpitis, volume of anaesthetic solution, the well as the quality of the individual randomized clini-
concentration of vasoconstrictor and speed of injec- cal trials included in each meta-analysis. For primary
tion. Systematic reviews published in language other research studies, researchers must adhere to CON-
than English were excluded, which creates a degree of SORT guidelines and should register their clinical trial
selection bias. Amongst the five reviews, four included in advance in clinical trial registries such as Clini-
randomized clinical trials with only adult patients, calTrials.gov, Health Canada Clinical Trial Database,
whereas Su et al. (2016) included both children Iranian Registry of Clinical Trials, EU Clinical Trials
(<16 years) and adult patients. Register and Australian New Zealand Clinical Trials
Flaws and inconsistencies at the primary research Registry.
level further complicates the interpretation within this
umbrella review, as the outcome measure used to assess Diagnosis – irreversible pulpitis.
the efficacy of local anaesthetic solutions in randomized 1. Randomized clinical trials comparing the anaes-
clinical trials varied between studies. In some clinical tri- thetic efficacy of various local anaesthetic solu-
als, local anaesthetic efficacy was assessed by pulp sensi- tions need to adhere to an accepted definition of
bility testing (cold test/electric pulp tester; Hsiao-Wu irreversible pulpitis; for example, the American
et al. 2007, Evans et al. 2008), whilst in others, efficacy Association of Endodontists (AAE 2013) defines
was assessed by asking the patient to indicate discom- irreversible pulpitis as ‘Symptomatic irreversible
fort/pain using a visual analogue scale (VAS) during pulpitis may include sharp pain upon thermal
access cavity preparation or pulp extirpation (Torta- stimulus, lingering pain (often 30 s or longer
mano et al. 2009, Aggarwal et al. 2017). Nusstein et al. after stimulus removal), spontaneity (unprovoked
(1998) reported 42% of posterior teeth that had pain) and referred pain. Sometimes the pain may
responded negatively to an electric pulp test were associ- be accentuated by postural changes such as lying
ated with pain during root canal treatment. Thus, pulp down or bending over and over-the-counter anal-
sensibility testing is not a reliable indicator for assessing gesics are typically ineffective’.
anaesthetic efficacy during actual treatment. The sys- 2. The presence or absence of an apical radiolucency/
tematic review by Kung et al. (2015) combined clinical widening of the apical periodontal ligament should
trials that assessed the outcome using pulp sensibility be included in the results. If teeth exhibiting an api-
tests and patient pain ratings, whereas Nagendrababu cal radiolucency are to be excluded, this must be
et al. (2019) combined studies only using a patient rat- made explicit and a clear rationale provided.
ing scale or VAS. This variation in outcome measures Details of the radiographic technique (e.g. imaging
creates uncertainty and confusion in the subsequent sys- type, exposure conditions, use of paralleling
tematic review, with the result that clinicians are unsure devices) and under what conditions the radio-
of the best anaesthetic solution to use during root canal graphs were interpreted must be included, for
treatment of teeth with irreversible pulpitis. example the experience of each examiner and the
degree of agreement (intrarater or interrater agree-
ment) if two or more examiners were involved in
Reporting deficiencies and gaps in knowledge/ the interpretation of radiographs.
methodology 3. Details of the clinical process for establishing a
On reviewing the randomized clinical trials and sys- pulpal diagnosis, as well as the techniques and
tematic reviews on the topic of anaesthetic efficacy, devices used for pulp sensibility testing (manufac-
several deficiencies in methodology and reporting turer, city, country), must be described accu-
were identified. To improve the quality of clinical tri- rately.
als and systematic reviews, the following recommen- 4. The experience of the operator(s) (undergraduate/
dations are proposed on their conduct and reporting. postgraduate/endodontist) who performed the
clinical examination, pulp sensibility tests and
Recommendations for conducting randomized clinical interpretation of radiographs to confirm the pulp
trials on anaesthetic solutions status must be provided. The operator who per-
forms the pulp sensibility tests should ideally be
Adhere to CONSORT guidelines. The quality of evidence independent of the research team. Even with a
from this umbrella review is affected by the quality of clear definition of irreversible pulpitis and an

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 13652591, 2020, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13215 by Cochrane Mexico, Wiley Online Library on [12/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Anaesthetic efficacy of articaine and lidocaine Nagendrababu et al.

independent evaluator of pulpal status, consis- tests may also have an effect with evidence that the
tently diagnosing irreversible pulpitis can be diffi- result of the first test may have an effect on the reac-
cult. Although, spontaneous, radiating pain that tion to subsequent tests to give a false-negative result
lingers after removal of the stimulus tends to indi- (Nusstein et al. 2010). Hence, a more reliable indica-
cate irreversible pulpitis (ESE 2019), it should be tor for assessing anaesthetic efficacy in clinical trials
remembered that this is a dynamic clinical diag- is to record pain during the endodontic procedure
nosis, which does not always accurately reflect (e.g. access cavity preparation, pulp tissue manipula-
the histological inflammatory state of the pulp tion, canal instrumentation). It would be best practice
(Dummer et al. 1980). Indeed, irreversible pulpitis to report the success of anaesthesia separately for
can be symptomless in anywhere between 14% access cavity preparation, initial pulp penetration and
and 60% of cases (Seltzer et al. 1963, Michaelson canal instrumentation procedures (Poorni et al.
& Holland 2002). This makes an accurate diag- 2011). Details of the individual(s) who performed the
nosis of irreversible pulpitis difficult and often root canal treatment procedure(s) must be described,
unreliable even for experienced operators, which for example, were they blinded to the experimental
adds a potential bias into a clinical trial. groups, how many operators were involved, their sta-
tus (undergraduate/postgraduate/endodontist) and
Inclusion/exclusion criteria. The selection criteria of their relative experience.
patients/volunteers must be described clearly. The age
of the patients, preoperative pain status and how it Clinical significance of the results. When planning ran-
was measured, radiographic status and medical and domized clinical trials comparing two local anaes-
dental history (such as history of trauma, previous thetic solutions, it is critical that the study is
restorative and orthodontic treatments, previous pain adequately powered. Several randomized clinical trials
from the tooth) are essential. Patients taking medica- that have compared articaine with lidocaine in teeth
tion that could interfere with the action of any of the with irreversible pulpitis and used a VAS to measure
anaesthetic solutions must be excluded and reasons pain during root canal instrumentation have reported
for their exclusion highlighted in the results section. a trend for more effective anaesthesia, albeit non-
significant, results with articaine (Poorni et al. 2011,
Anaesthetic solution. Details of the anaesthetic solu- Sood et al. 2014, Allegretti et al. 2016). For example,
tions must be provided including volume, concentra- Sood et al. (2014) reported 88% success with arti-
tion, vasoconstrictor used and temperature when caine and 82% success with lidocaine, whilst Poorni
injected. et al. (2011) reported 69% with articaine and 65%
with lidocaine, and Allegretti et al. (2016) 63.6% for
Delivery of anaesthetic solution. The length and gauge articaine and 54.5% for lidocaine. In addition to the
of the needle used to deliver the anaesthetic solution lack of statistical significance, the number of partici-
(s) must be provided as well as the estimated average pants was also relatively small (<55 patients in each
injection speed. arm) increasing the potential for type II error as the
studies were underpowered. It is essential that new
Blinding. The blinding method and individuals studies investigating articaine and lidocaine use previ-
involved in the blinding process must be described ously published percentage differences to establish the
fully including operator, patient and evaluator. sample size.

Time before intervention. The period between delivery Adverse events. The occurrence of adverse event(s)
of an anaesthetic solution and the assessment of during clinical trials and how they are managed must
anaesthetic efficacy must be standardized and be carefully described. If no adverse event(s) occur,
reported (e.g. lip numbness, patient self-reported this should also be mentioned.
assessment [Visual Aanalog Scale]).
Recommendations for conducting systematic reviews and
Outcome measure. In teeth with irreversible pulpitis, meta-analyses on anaesthetic solutions
the lack of a response to pulp sensibility tests might The quality of evidence from this umbrella review is
not guarantee profound pulpal anaesthesia for pain- affected by the methodological and reporting quality
less treatment. The waiting time between sensibility of the included systematic reviews and meta-analyses.

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Nagendrababu et al. Anaesthetic efficacy of articaine and lidocaine

All systematic reviews and meta-analyses must It is hoped that these recommendations will help
adhere to the AMSTAR and PRISMA guidelines and researchers to effectively plan and design randomized
additionally authors need to consider the following clinical trials and systematic reviews for the benefit of
parameters, whilst conducting and reporting system- clinicians and patients and also help to increase the
atic reviews and meta-analyses on local anaesthetic accuracy, validity and credibility of publications
solutions: through the development of high-quality manuscripts.
1. The results of the scientific quality assessment Finally, it must be emphasised that even when using
(risk of bias) of the primary randomized trials articaine the problem of achieving pulp anaesthesia
they include and use that information to formu- has not been solved completely and supplementary
late the conclusions; anaesthetic techniques to achieve successful pulp
2. subgroup and sensitivity analysis based on out- anaesthesia in many cases of irreversible pulpitis will
come measures (pulp sensibility, record pain dur- be required, regardless of the primary injection and
ing the endodontic procedure) and local solution employed.
anaesthetic solution (volume, concentration,
vasoconstrictor used and temperature);
3. evaluation of adverse events associated with com-
Conflict of interest
monly used local anaesthetic solutions; The authors have stated explicitly that there are no
4. a clear and consistently applied definition of pul- conflicts of interest in connection with this article.
pal status must be used.
These recommendations will help to increase the
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efficacy of 4% articaine with 1: 100,000 epinephrine and
Additional Supporting Information may be found in
2% lidocaine with 1: 80,000 epinephrine for inferior alve-
the online version of this article:
olar nerve block in patients with irreversible pulpitis. Jour-
Table S1. AMSTAR score for included SRs and
nal of Clinical and Experimental Dentistry 6, e520–3.
Srinivasan N, Kavitha M, Loganathan CS, Padmini G (2009) MA.
Comparison of anesthetic efficacy of 4% articaine and 2%

© 2019 International Endodontic Journal. Published by John Wiley & Sons Ltd International Endodontic Journal, 53, 200–213, 2020 213