CONSORT Randomized Clinical Trial
Comparison of the Anesthetic Efficacy
of Mepivacaine and Lidocaine in Patients
with Irreversible Pulpitis: A Double-blind
Randomized Clinical Trial
Renata Pieroni Visconti, DDS, MSc, Isabel Peixoto Tortamano, DDS, MSc, PhD,
and In^es Aparecida Buscariolo, DDS, MSc, PhD
Abstract
Introduction: The objective of this study was to
compare the anesthetic efficacy of 2% mepivacaine
combined with 1:100,000 epinephrine with 2% lido-
caine combined with 1:100,000 epinephrine during pul-
pectomy of mandibular posterior teeth in patients with
irreversible pulpitis. Methods: Forty-two patients with
irreversible pulpitis who were admitted to the Emer-
gency Center at the University of S~ao Paulo School of
Dentistry volunteered to take part in the study and
were randomized to receive conventional inferior alve-
olar nerve block containing 1.8 or 3.6 mL of either 2%
mepivacaine with 1:100,000 epinephrine or 2% lido-
caine with 1:100,000 epinephrine. We recorded pa-
tients subjective assessments of lip anesthesia,
absence/presence of pulpal anesthesia tested by using
electric pulp stimulation, and absence/presence of pain
during the subsequent pulpectomy by using a verbal
analogue scale. Results: All patients tested reported
lip anesthesia after application of either type of inferior
alveolar nerve block. Pulpal anesthesia success rates
measured by using the pulp tester were satisfactory
for both solutions (86% for mepivacaine and 67% for
lidocaine). Success rates according to patient report of
no pain or mild pain during pulpectomy were higher
for mepivacaine solution (55%) than for lidocaine solu-
tion (14%). The differences between mepivacaine and
lidocaine were statistically significant. Conclusions:
Mepivacaine resulted in effective pain control during
irreversible pulpitis treatments. The success rates with
either solution were not high enough to ensure com-
plete pulpal anesthesia. (J Endod 2016;42:13141319)
Key Words
Inferior alveolar nerve block, irreversible pulpitis, lido-
caine, mepivacaine
From the Department of Stomatology, Integrated Clinical Discipline, University of S~ao Paulo School of Dentistry, S~ao Paulo, S~ao Paulo, Brazil.
Address requests for reprints to Dr Renata Pieroni Visconti, University of S~ao Paulo School of Dentistry, Stomatology, S~ao Paulo, SP, Brazil. E-mail address:
ativaodontologia@gmail.com
0099-2399/$ - see front matter
Copyright 2016 American Association of Endodontists.
http://dx.doi.org/10.1016/j.joen.2016.06.015
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P ain is an unpleasant
sensation of varying in-
tensity associated with a
Signicance
In this article we report a randomized blind
controlled trial that used mepivacaine, which is
current or potential pro-
rarely explored in the literature for this purpose.
cess of tissue destruction.
This article represents original material, which
It is difficult to determine
was not previously published.
the intensity of pain sensa-
tions because there is an
emotional element (1), and each patient has a different threshold (2) involving both
subjectivity and previous experiences.
In irreversible pulpitis, the cause of pain is acute pulp inflammation. Certain
changes can be observed such as vasodilation, increased vascular permeability, and
leakage of leukocytes. Because the pulp is unable to expand, inflammation produces
a significant increase in internal tissue pressure (3).
Emergency control of irreversible pulpitis involves executing endodontic treat-
ment to relieve pain (3, 4), and pain control is critical in these procedures (1, 2,
512).
Mepivacaine and lidocaine are both classified as amides and are the most
commonly used solutions in dentistry, and there are 50 years of accumulated experi-
ence showing their effectiveness and safety for providing regional anesthesia for dental
treatment (13).
Mepivacaine is routinely used in painful clinical situations because it has a lower
ionization constant (pKa) than lidocaine and is therefore more compatible with in-
flamed tissues and has a shorter onset and longer duration of anesthesia.
Even in healthy teeth, inferior alveolar nerve (IAN) blocks are not always success-
ful. Success rates reported in studies vary from 62% to 96% (1, 69, 1416), and they
do not always ensure the success of the clinical procedure involved (15, 17), especially
in cases of irreversible pulpitis (2, 5, 7, 9, 11, 1416, 1825).
The failure rate of IAN blocks is even higher in irreversible pulpitis, ranging from
37% to 85%, according to several different authors (1, 5, 7, 11, 12, 1416, 18, 19, 22
27).
Many studies (1, 8, 9, 15, 16, 18, 19, 2325, 28, 29) have shown that achieving
soft tissue anesthesia does not guarantee the effectiveness of the block or a painless
clinical procedure. The fact that patients often feel pain during endodontic treatment
of teeth with irreversible pulpitis is a challenge for the clinician and the patient (1).
JOE Volume 42, Number 9, September 2016

Even if the block is confirmed by a negative response to electrical
testing, there is still a possibility that supplementary anesthesia will be
required. In other words, the block may have been achieved and tested,
but only at the time of pulpectomy will the need for additional anesthesia
be known on the basis of pain reported by the patient (2, 5, 11, 14, 18,
19, 22).
Even when supplementary techniques are used to increase the
effectiveness of the blocking procedure, pulpectomy that is totally pain-
less and comfortable for the patient is unachievable (6, 7, 10, 19, 21,
24, 25, 30).
There are a number of hypotheses to attempt to explain the
reduced effectiveness in teeth that are already painful (2, 4, 3133),
such as larger quantities of substance P in teeth with pulpitis and
increased expression of sodium channels. However, the subject still
needs to be studied further to achieve a better understanding.
In view of the lack of studies investigating mepivacaine, the objec-
tive of this study was to compare the anesthetic efficacy of 2% mepiva-
caine with that of 2% lidocaine, both administered in conjunction with
1:100,000 epinephrine, for IAN block in patients with irreversible pul-
pitis of mandibular posterior teeth.
Materials and Methods
Forty-two adult volunteer subjects who presented at the Emer-
gency Center at the University of S~ao Paulo School of Dentistry took
part in this prospective, randomized, double-blind study.
Inclusion criteria for volunteers were age from 18 to 50 years,
currently feeling pain, good health, and not taking any medication
that would alter perception of pain, which were determined by verbal
questioning and a written questionnaire. The research was approved
by the University of S~ao Paulo School of Dentistry Human Research
Ethics Committee (protocol 67/08), and informed consent was ob-
tained from each patient in writing.
In addition, to qualify for our study, patients had to be clinically
diagnosed with irreversible pulpitis on the basis of moderate to severe
spontaneous pain and prolonged response exhibited to cold testing with
Endo-Frost (Coltene-Roeko, Langenau, Germany) and a positive
response to the electric pulp test (Vitality Scanner 2006; SybronEndo,
Orange, CA).
Each participant had at least 1 adjacent tooth plus a healthy contra-
lateral canine or, alternatively, a contralateral canine without deep
caries damage, extensive restoration, advanced periodontal disease,
history of trauma, or sensitivity. Electric pulp stimulation of the contra-
lateral canine, which had not been anesthetized, was used as a control to
ensure that the equipment was working properly and that patients were
responding as expected. All preinjection and postinjection tests were
conducted by trained personnel who were blinded to the anesthetic vol-
umes administered. Electrocardiogram gel was applied to the probe tip,
which was placed in the middle third of the buccal surface of the tooth
being tested. The current rate was set to take 25 seconds to increase
from zero output (0) to maximum output (80 mA). The reading in
mA that was shown when the patient reported the first sensation was re-
corded.
Patients were asked to rate their current pain on the following 4-
point scale: 0, no pain; 1, mild pain (ie, pain that was recognizable but
did not cause discomfort); 2, moderate pain (ie, pain that was causing
discomfort but was bearable); and 3, severe pain (ie, pain that caused
considerable discomfort and was difficult to bear). Only patients with
moderate to severe pain were included in this study.
Patients were administered standard IAN block injections of 2%
mepivacaine or 2% lidocaine, both combined with 1:100,000
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CONSORT Randomized Clinical Trial
epinephrine (DFL Industria e Comercio Ltda, Rio de Janeiro, RJ,
Brazil). The same person administered all injections.
Blinding was achieved as follows: 3 cartridges (1.8 mL each) of
each anesthetic solution were sealed in 42 envelopes by the first author.
The senior researcher, who was not involved in the endodontic proce-
dure, administered the anesthesia injection after choosing 1 of the en-
velopes at random. Electric pulp stimulations to assess pulpal
anesthesia and the pulpectomy were performed by a postgraduate stu-
dent to guarantee that the anesthetic solution remained unknown and
thus maintain the double-blindness of the study.
Injections were performed by using a side-loading carpule syringe
fitted with 27-gauge 0.4  35 mm needle (Injex Industrias Cirurgicas
Ltda, S~ao Paulo, SP, Brazil) and equipped with a blood aspiration device
and a thumb ring (Konnen; Kennen Industria e Comercio Ltda, S~ao
Paulo, SP, Brazil). Blood aspiration tests were carried out before
each anesthesia injection and after changing needle position.
The first 2 cartridges of the anesthetic solution were administered
by using an indirect three-position technique as follows. In the first step
of the first attempt to achieve anesthesia (1 cartridge, 1.8 mL), the nee-
dle was introduced 35 mm deep, blood was aspirated, and approxi-
mately 0.3 mL anesthetic solution was injected. In the second step,
the syringe was moved to the premolar region on the opposite side,
where the needle was inserted until it made contact with bone. The nee-
dle was then withdrawn 12 mm, blood was aspirated, and the remain-
ing 1.5 mL anesthetic solution was slowly injected. The average injection
time for each cartridge was approximately 2 minutes.
Ten minutes after the initial IAN block procedure, each patient was
asked whether his/her lip was numb. The electric pulp test was repeated
on the tooth with pulpitis and the adjacent tooth to ensure the nerve
blockage had been successful. The criterion used to determine whether
pulp anesthesia had been successful was 2 consecutive negative re-
sponses to the maximum pulp stimulus (80 mA). Experimentally, the
80 reading is an end point that can be used to measure complete
pulp anesthesia over time.
If profound lip numbness was not recorded within 10 minutes and
the electric pulp tester did not reach maximum output without the pa-
tient reporting pain, the block was considered unsuccessful, and
another cartridge (1.8 mL) of the same anesthetic solution was reap-
plied with the same technique used before. Another 10 minutes were
allowed to elapse, and then the electric pulp test was repeated and signs
of lip anesthesia were observed. If profound lip numbness was not re-
corded or, most importantly, the electric pulp tester did not reach
80 mA without provoking sensation, the patients were excluded from
the study.
Immediately before the pulpectomy, electric pulp stimulation tests
were repeated to determine pulpal anesthesia. Patients were also in-
structed to report any painful discomfort during the pulpectomy proce-
dure. The intensity of any pain felt during the pulpectomy was evaluated
by using the same 4-point scale described above.
Efficacy of anesthesia was defined as successful if the dentist was
able to access the pulp chamber without the patient reporting pain (pain
scores 0 or 1). In these cases, the pulpectomy procedure was
continued. If the patient scored pain as 2 or 3, the efficacy of anesthesia
was classified as unsuccessful. In these cases, the extent of access
achieved was recorded as within dentin, pulp chamber, or root canal,
and intraligamentary or intrapulpal anesthesia was administered, de-
pending on the level of the site of pain, and then the pulpectomy was
finalized. The success rates of these complementary techniques are
far beyond the scope of this article.
Findings were recorded in a Microsoft Excel spreadsheet (Micro-
soft Office Excel 2003; Microsoft Corp, Redmond, WA) before statistical
evaluation by using the program GMC software, version 2002
Mepivacaine and Lidocaine in Irreversible Pulpitis 1315
CONSORT Randomized Clinical Trial
(FORP-USP, Ribeir~ao Preto, SP, Brazil). The Fisher exact test (2-tailed)
was chosen as an appropriate statistical instrument for the purposes of
this study. This test is a form of the c2 analysis that only evaluates
P values.
Results
There were no statistically significant differences between the pa-
tients in the 2 test groups in this study in terms of gender distribution,
age (mean age: mepivacaine group, 26 years; lidocaine group,
28 years), the types of teeth with irreversible pulpitis, or the average
baseline response to the electric pulp test (Table 1). The groups
were therefore considered homogeneous, and thus the results obtained
with both anesthetic solutions can be directly compared.
All patients reported subjective lip anesthesia 10 minutes after the
IAN block. From the original sample of 42 patients, 10 patients, 3 from
the mepivacaine group and 7 from the lidocaine group, did not reach
maximum output of the electric pulp tester without feeling pain even af-
ter the second cartridge and were excluded from the study (Fig. 1).
After injection of the first cartridge (1.8 mL), 11 patients in the me-
pivacaine group (52%) and 7 patients in the lidocaine group (33%)
exhibited pulpal anesthesia, ie, a negative response to the electrical
stimulus. After the second cartridges, another 7 patients in the mepiva-
caine group (86%) and 7 patients in the lidocaine group (67%) ex-
hibited pulpal anesthesia. Table 2 contains a comparison of the
percentages of IAN block success (pulpal anesthesia) in teeth with pul-
pitis and healthy teeth after administration of both volumes. There were
no statistically significant differences between the 2 experimental
groups (P value).
During pulpectomy, 8 patients in the mepivacaine group and 12
patients in the lidocaine group reported pain (pain scores 2 and 3).
This time the slight difference was statistically significant (P < .05)
(Fig. 2).
None of the patients given mepivacaine required an intraligamen-
tary injection; only intrapulpal administration was needed. One of the
lidocaine patients needed an intraligamentary injection because he
felt pain during dentin access.
Discussion
In this study only lower molars (predominantly the first and sec-
ond molars) were included to avoid variations in innervation (1), as
was also the case in several other studies (1, 12, 16, 2325, 27),
although some authors (8, 11, 14, 19, 22) have investigated lower
molars and premolars together. Fowler et al (2) studied the effect of
different volumes of 2% lidocaine in 375 premolars and molars with
irreversible pulpitis. They concluded that there is no difference between
the groups of teeth.
TABLE 1. Comparison of Age, Sex, Type of Teeth, and Mean Baseline Electric
Pulp Tester Results
Mepivacaine Lidocaine
Age (y) 26  10 28  11
Sex
Men 3 6
Women 18 16
Tooth, molar
First 12 9 cally significant (P < .05) when up to 2 carpules were used to achieve
Second 6 9
Third 3 3
Mean baseline electric 38 39
pulp tester results (mA)
There were no significant differences (P > .05) between the groups.
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It is difficult to define anesthetic success, and the subject itself is
controversial. Many researchers limit their analyses to the superficial
effects, but others have been highly meticulous in this respect (24).
Different studies have used a variety of different tests such as numbness
of lips and tongue (11, 14, 26, 27), visual analogue pain scales (2, 12,
18), and lack of response to cold stimuli (1, 6, 8, 12, 14, 18, 24) or to
electrical testing (7, 9, 15, 21, 25).
There are few studies in the literature that have used the anesthetic
salt mepivacaine. Rodrguez-Wong et al (24) compared 2% mepiva-
caine alone against 2% mepivacaine combined with tramadol (a cen-
trally acting opioid) in irreversible pulpitis cases. In a control group,
1.8 mL 2% mepivacaine used in isolation resulted in pulpal anesthesia
efficacy of 67.9% when the criterion was a negative response to a cold
test and of 53.6% when the criterion was access to the hard tissues of the
tooth with pulpitis without the patient reporting pain (24). We observed
52% for the electrical test criterion. Rodrguez-Wong et al observed a
46.4% blockage success rate during the pulpectomy, which is very close
to the 54% anesthesia efficacy observed in our mepivacaine group.
Cohen et al (1) compared the efficacy of 3% mepivacaine without a
vasoconstrictor against 2% lidocaine with 1:100,000 epinephrine in
molars with irreversible pulpitis. The efficacy of pulpal anesthesia
was assessed by numbness of lip and tongue and negative response
to a temperature test, resulting in 61% for the mepivacaine group
and 63% for the lidocaine group. They were able to conduct the pulpec-
tomy without pain and without supplementary anesthetic in 55% of the
sample for both solutions. In the present study, the group that was given
the same volume (1.8 mL) of mepivacaine as that administered by Co-
hen et al exhibited a pulpal anesthesia rate of 33%. This lower rate is the
result of the criterion chosen to define successful pulpal anesthesia. Our
results for successful, pain-free pulpectomy are similar, because with a
single carpule of 2% mepivacaine we achieved 54% success, although
we used different concentrations of the anesthetic and of the vasocon-
strictor.
There are no other clinical studies in the literature that have
compared the efficacy of 2% mepivacaine for cases of irreversible pul-
pitis, and so we have included studies that used 2% lidocaine combined
with epinephrine in the comparative analysis of results.
The anesthetic technique (25) used in this study proved to be
adequately effective, because it resulted in pulpal anesthesia in 76%
of the whole sample of patients with irreversible pulpitis, 86% of the pa-
tients in the mepivacaine group and 67% of those in the lidocaine group
(Table 2).
For both solutions, increasing the volume of anesthetic increased
the rate of pulpal anesthesia, but without statistical difference between
the 2 volumes, as has been reported in previous studies (12, 15, 18,
26). However, from a clinical perspective, mepivacaine exhibited
superior performance. Aggarwal et al (27) observed a statistically sig-
nificant improvement when volume was increased, which may be
because of the larger number of cases assessed (319 molars with irre-
versible pulpitis). In a recent study by using articaine Abazarpoor et al
(18) show that there is an improvement in performance of the block
when the second cartridge is injected, although complete control of
pain is not always achieved, requiring additional anesthetic during
the procedure.
Pain was reported with greater frequency in the lidocaine group,
and the difference compared with the mepivacaine group was statisti-
IAN block. In contrast, the electric pulp testing results for the healthy
control teeth were very similar for lidocaine and mepivacaine at 90%
and 95% success, respectively (Table 2). These data, in conjunction
with results reported in the literature, lead us to suspect that teeth
that are already painful exhibit different nociceptive behavior to
JOE Volume 42, Number 9, September 2016
 CONSORT Randomized Clinical Trial
Painful teeth n=42

Mepivacaine n=21 Lidocaine n=21

1st cartridge (1.8 mL)

EPT - EPT + EPT + EPT -

n=11 n=10 n=14 n=7

Efficacy of Efficacy of
anesthesia 54% anesthesia 0%

2nd cartridge (3.6 mL)

EPT - EPT + EPT + EPT -

n=7 n=3 n=7 n=7

Efficacy of Efficacy of
anesthesia 55% anesthesia 14%

Figure 1. Outline of the experimental procedures and results for efficacy of anesthesia during pulpectomy. Efficacy of anesthesia, dentist was able to access the
pulp chamber without pain; EPT , electric pulp test negative (pulpal anesthesia successful); EPT+, electric pulp test positive (pulpal anesthesia unsuccessful).

asymptomatic teeth, but even so, mepivacaine was more compatible and of the results, they concluded that both anesthetics are equally effective
effective. when used for mandibular block or maxillary infiltration.
In this study, lidocaine achieved a pulpal anesthesia rate of 67%, The degree of pulpal anesthesia success observed in this study ap-
but the IAN block success rate was only 14%. Mepivacaine exhibited pears to be sufficient for less invasive procedures, but not to enable
greater efficacy for pulpal anesthesia (86%) and a higher IAN block suc- intervention in pulpitis (2). Therefore, addition of the second carpule
cess rate (55%). These rates demonstrate that pulpal anesthesia does is warranted as long as there is evidence that pulpal anesthesia has been
not guarantee a painless clinical procedure (2, 6, 8, 11, 14, 16, 19, achieved, because this may be better used as supplementary anesthetic,
22, 23, 25, 30). which to date appears to be indispensable in irreversible pulpitis, in
Our results for the lidocaine group are in line with data in the liter- contrast with other authors (7, 9, 25) who have started with 3.6 mL.
ature (7, 22, 23, 25), despite minor variations between different It is safer to use smaller volumes and perform the anesthetic
studies. The success of pulpal anesthesia confirmed by the electrical
test varies from 43% to 70%, and the pain-free pulpectomy rate falls
within the reported range of 13%31%.
Differences in criteria for initial pulpal anesthesia, types of teeth,
populations of patients, and anesthetic volumes and concentrations
are probably responsible for the large variations in success rates be-
tween different studies (5, 11, 14).
To compile the various results and methodology of irreversible
pulpitis, Kung et al (5) conducted a systematic review and meta-
analysis to elucidate what is the effectiveness of articaine compared
with lidocaine in pain reduction in cases of endodontic treatment for
irreversible pulpitis. Following a rigorous methodology and analysis

TABLE 2. Comparison of Percentage Success of IANB Block (pulp anesthesia)

in Teeth with Pulpitis and in Healthy Teeth
Teeth with pulpitis (%) Healthy teeth (%)
Figure 2. Bar graph illustrating proportion of patients feeling pain during
Mepivacaine 18 of 21 (86) 20 of 21 (95)
Lidocaine 14 of 21 (67) 19 of 21 (90) pulpectomy after IAN block with 1 of 2 different solutions (2% mepivacaine
with 1:100,000 epinephrine or 2% lidocaine with 1:100,000 epinephrine).
There was no significant difference (P > .05) between the groups. *P < .05.

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CONSORT Randomized Clinical Trial
technique correctly, thereby reducing the risk of toxicity and providing
greater security for patient and professional (13).
With regard to the depth that was attained during endodontic ac-
cess, mepivacaine made it possible to get closer to the pulp chamber. In
1 case in the lidocaine group it was necessary to perform intraligamen-
tary injection before the intrapulpal injection. This contrasts with results
reported in the literature (11, 14, 19, 22), where intercurrent
conditions in the dentin outweighed those in the pulp and root. One
possible reason why this may have occurred is that we only analyzed
molars, whereas other studies investigated molars and premolars.
The depth attained is of relevance because the type of supplementary
analgesia administered depends on the site of pain (11, 14). Each
technique has its peculiarities with relation to discomfort during
administration, efficacy, and side effects, but these subjects are
beyond the scope of this article.
Hypotheses that have been raised to explain the routine lack of
success with anesthetic blocks attribute failure to decay of the pain
threshold for apprehensive patients (2), to variations in pH (7, 8,
32), to the physical and chemical properties of the anesthetic, to
activity of inflammatory mediators, and to the inflammation itself and
its pathophysiological components (4, 6, 32, 33). Inflammatory
mediators and neuropeptides (32, 33) play an important role in
sensitization and in reducing the threshold of the nerve fibers (4, 6,
20, 34), stimulating and intensifying pain and probably making
successful anesthetic block less likely in the presence of irreversible
pulpitis. Studies have shown that inflamed pulp expresses large
quantities of prostaglandins and substance P (31, 32). Another factor
to be taken into consideration is related to voltage-gated sodium chan-
nels (35), which can be elevated in the pulp of teeth with irreversible
pulpitis (34) by up to 6 times (4). An in vitro study conducted by Po-
tocnik et al (20) showed that local anesthetic provokes total disappear-
ance of the action potential of C fibers, but not of A fibers. These findings
may have a connection with anesthetic inefficacy in pulpitis, because
there are large quantities of A fibers in the dental pulp, originating
from the trigeminal nerve (34).
The drop in pH seen in inflamed pulp may interfere with dissoci-
ation of the anesthetic, and if this is the case, the fact that mepivacaine
has an ionization constant (pKa) of 7.6, which is lower than that of lido-
caine at 7.9, may mean that a greater quantity of the free base is able to
cross the nerve sheath, with the result that the nerve stimulus is more
completely interrupted (13, 29). This would in part explain the
better performance of mepivacaine.
Further research that correlates the neurophysiology of inflamed
pulp with the performance of mepivacaine should be conducted to
improve understanding and elucidate failure of anesthesia in irrevers-
ible pulpitis.
Conclusion
At smaller volumes (1 cartridge), mepivacaine was more effective
for achieving IAN block (for pulpectomy) than lidocaine. With fewer
additional injections and smaller volumes, mepivacaine made it
possible to get closer to the pulp tissue (pulp chamber), providing
greater clinical comfort than lidocaine. We suggest that the sample
should be increased to improve these results.
Acknowledgments
The authors deny any conflicts of interest related to this study.
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