CONSORT Randomized Clinical Trial
A Prospective, Randomized, Double-blind Comparison of 2%
Lidocaine With 1:100,000 and 1:50,000 Epinephrine and 3%
Mepivacaine for Maxillary Infiltrations
Rick Mason, DDS, MS,* Melissa Drum, DDS, MS,† Al Reader, DDS, MS,† John Nusstein, DDS, MS,†
and Mike Beck, DDS, MA‡
Abstract
Introduction: The purpose of this prospective, random-
ized, double-blind crossover study was to evaluate the
anesthetic efficacy of 2% lidocaine with 1:100,000 and
1:50,000 epinephrine and 3% mepivacaine in maxillary
lateral incisors and first molars. Methods: Sixty subjects
randomly received, in a double-blind manner, maxillary
lateral incisor and first molar infiltrations of 1.8 mL of
2% lidocaine with 1:100,000 epinephrine, 2% lidocaine
with 1:50,000 epinephrine, and 3% mepivacaine at
three separate appointments spaced at least 1 week
apart. The teeth were pulp tested in 3-minute cycles
for a total of 60 minutes. Results and Conclusions:
Anesthetic success and the onset of pulpal anesthesia
were not significantly different between 2% lidocaine
with either 1:100,000 or 1:50,000 epinephrine and 3%
mepivacaine for the lateral incisor and first molar.
Increasing the epinephrine concentration from
1:100,000 to 1:50,000 in a 2% lidocaine formulation
significantly decreased pulpal anesthesia of short dura-
tion for the lateral incisor but not the first molar. For
both the lateral incisor and first molar, 3% mepivacaine
significantly increased pulpal anesthesia of short dura-
tion compared with 2% lidocaine with either
1:100,000 or 1:50,000 epinephrine. (J Endod 2009;35:
1173–1177)
Key Words
Epinephrine, infiltration, lidocaine, maxillary, mepiva-
caine
From *Private Practice, State College, PA; and the Divisions
of †Endodontics and ‡Oral Biology, The Ohio State University,
Columbus, OH.
Address requests for reprints to Dr Melissa Drum, Division
of Endodontics, College of Dentistry, The Ohio State University,
305 West 12th Avenue, Columbus, OH 43210. E-mail address:
drum.13@osu.edu.
0099-2399/$0 - see front matter
Copyright ª 2009 American Association of Endodontists.
doi:10.1016/j.joen.2009.06.016
JOE — Volume 35, Number 9, September 2009
M axillary infiltration anesthesia is a common method to anesthetize maxillary teeth.
Previous studies (1–17) have evaluated the success of maxillary infiltrations using
the electric pulp tester. Using a volume of 1.8 mL or less and various anesthetic formu-
lations, pulpal anesthetic success (obtaining maximum output with an electric pulp
tester) ranged from 62% to 100%.
Although increasing the concentration of epinephrine in an inferior alveolar nerve
block did not result in increased success (18), Knoll-Köhler and Förtsch (6) found that
an increase in epinephrine concentration prolonged anesthetic duration in the maxil-
lary incisor. The current study evaluated if increasing the epinephrine concentration
would prolong the duration of pulpal anesthesia in both the lateral incisor and first
molar.
Three percent mepivacaine has been found to be equivalent to 2% lidocaine with
1:100,000 epinephrine for inferior alveolar nerve blocks (19, 20). Aberg and Sydnes
(21) reported an 89% success rate of 3% mepivacaine for maxillary lateral incisor infil-
tration. Burns et al (22) studied the palatal-anterior superior alveolar nerve block and
found that 3% mepivacaine was significantly less effective than 2% lidocaine with
1:100,000 epinephrine. The current study evaluated if 3% mepivacaine would be effec-
tive for pulpal anesthesia in both the lateral incisor and first molar.
Although a number of studies have evaluated infiltration injections in the posterior
maxilla (4, 5, 9, 12–15), none have evaluated 2% lidocaine with 1:50,000 epinephrine
or 3% mepivacaine. Because anesthesia may vary between the anterior and posterior
maxilla, it would be of interest to study posterior infiltration anesthesia.
The efficacy of 2% lidocaine with 1:100,000 and 1:50,000 epinephrine and 3%
mepivacaine in providing pulpal anesthesia when administered to human maxillary
teeth needs further investigation to ensure their appropriate clinical use. The purpose
of this prospective, randomized, double-blind crossover study was to evaluate the anes-
thetic efficacy of 2% lidocaine with 1:100,000 and 1:50,000 epinephrine and 3%
mepivacaine in maxillary lateral incisors and first molars.
Materials and Methods
Sixty adult subjects participated in this study. All subjects were in good health and
were not taking any medication that would alter pain perception as determined by
a written health history and oral questioning. Exclusion criteria were as follows:
younger than 18 or older than 65 years of age, allergies to local anesthetics or sulfites,
pregnancy, history of significant medical conditions, taking any medications that may
affect anesthetic assessment, active sites of pathosis in area of injection, and inability
to give informed consent. The Ohio State University Human Subjects Review Committee
approved the study, and written informed consent was obtained from each subject.
Using a crossover design, 30 subjects received three maxillary lateral incisor infil-
trations, and 30 subjects received three maxillary first molar infiltrations at three sepa-
rate appointments spaced at least 1 week apart. For each lateral incisor or first molar,
the three infiltrations consisted of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine,
1.8 mL of 2% lidocaine with 1:50,000 epinephrine, and 1.8 mL of 3% mepivacaine.
With the crossover design, 90 infiltrations were administered for the lateral
incisor, and 90 infiltrations for the first molar and each subject served as his/her
Comparison of 2% Lidocaine with Epinephrine and Mepivacaine for Maxillary Infiltrations 1173
CONSORT Randomized Clinical Trial
TABLE 1. Percentages and Number of Subjects who Experienced Anesthetic
Success
2% lidocaine 2% lidocaine
(1:100,000 (1:50,000 3%
epinephrine) epinephrine) mepivacaine
Lateral 100 (30/30) 100 (30/30) 93 (28/30)
incisor
(%)*
First 97 (29/30) 93 (28/30) 93 (28/30)
molar
(%)*
*There were no significant differences (p < 0.05) among the solutions.
own control. Fifteen maxillary right lateral incisors and 15 maxillary left
lateral incisors were used. Fifteen maxillary right molars and 15 maxil-
lary left molars were used. The same side chosen for the first infiltration
was used again for the second and third infiltration. The same tooth was
used at the three visits for each anesthetic solution. The contralateral
canine was used as the control to ensure that the pulp tester was oper-
ating properly and that the subject was responding appropriately. A
visual and clinical examination was conducted to ensure that all teeth
were free of caries, large restorations, crowns, and periodontal disease
and that none had a history of trauma or sensitivity.
Before the injections at all of the appointments, the experimental
tooth and the contralateral canine (control) were tested three times
with the electric pulp tester (Analytic Technology Corp, Redmond,
WA) to obtain baseline information. The teeth were isolated with cotton
rolls and dried with an air syringe. Toothpaste was applied to the probe
tip, which was placed in the middle third of the facial or buccal surface
of the tooth being tested. The value at the initial sensation was recorded.
The current rate was set at 25 seconds to increase from no output (0) to
the maximum output (80). Trained personnel, who were blinded to the
anesthetic solutions, administered all preinjection and postinjection
tests.
Before the experiment, the three anesthetic solutions were
randomly assigned to designate which anesthetic solution was to be
administered at each appointment. Only the random numbers were re-
corded on the data-collection sheets to further blind the experiment.
Under sterile conditions, the 2% lidocaine cartridges with
1:100,000 epinephrine (Xylocaine; Astra Pharmaceutical Products,
Inc., Worchester, MA), the 2% lidocaine cartridges with 1:50,000
epinephrine (Xylocaine), and 3% mepivacaine cartridges (Carbocaine;
Graham Chemical Corp, Jamaica, NY) were masked with opaque labels,
and the cartridge caps and plungers were masked with a black felt tip
marker. The corresponding random code number was written on each
cartridge label. All anesthetic solutions were checked to ensure that the
anesthetic solution had not expired.
A standard maxillary infiltration injection was administered with
an aspirating syringe and a 27-G 1-inch needle (Sherwood Medical
Co, St Louis, MO). The target site was centered over the root apex of
the maxillary lateral incisor or between the mesiobuccal and distobuc-
cal root apices of the maxillary first molar. The needle was gently placed
into the alveolar mucosa with the bevel toward bone and advanced until
the needle was estimated to be at or just superior to the apex of the
lateral incisor or the apices of the first molar. The anesthetic formula-
tion was deposited over a period of 1 minute. All infiltrations were given
by the senior author (RM).
The depth of anesthesia was monitored with the electric pulp
tester. At 1 minute after the infiltration injection, pulp test readings
were obtained for the experimental tooth (first molar or lateral incisor)
and the contralateral maxillary canine. The testing continued in
1174 Mason et al.
3-minute cycles for a total of 60 minutes. At every third cycle, the control
tooth, the contralateral canine, was tested by an inactivated electric pulp
tester to test the reliability of the subject (ie, if the subject responded
positively to an inactivated pulp tester, then they were considered not
reliable and could not be used in the study).
No response from the subject at the maximum output (80 reading)
of the pulp tester was used as the criterion for pulpal anesthesia. Anes-
thesia was considered successful when two consecutive 80 readings
with the pulp tester were obtained within 10 minutes after the infiltra-
tion. The onset of anesthesia was defined as the first of two consecutive
80 readings. Anesthesia was classified as short duration if the subject
achieved two consecutive 80 readings, lost the 80 reading, and never
regained it within the 60-minute period. Assuming a 50% anesthetic
success rate and a nondirectional alpha risk of 0.05, a sample size of
30 subjects would be required to show a change in anesthetic success
of 25 percentage points with a power of 0.80.
The data were analyzed statistically. Group comparisons among
the lidocaine formulations and the mepivacaine formulation for anes-
thetic success and short duration of anesthesia were analyzed using
multiple McNemar tests. All values were adjusted using the step-down
Bonferroni method of Holm. The onset of anesthesia was assessed using
a one-way repeated measures analysis of variance. Comparisons were
considered significant at p < 0.05.
Results
For the lateral incisor, 15 men and 15 women ranging in age from
19 to 43 years, with an average age of 25 years, participated in this study.
For the first molar, 16 men and 14 women ranging in age from 20 to 42
years, with an average age of 25 years, participated.
Table 1 shows the percentages of successful pulpal anesthesia. The
success rates ranged from 93% to 100%. There was no significant
difference among the anesthetic formulations. The onset of pulpal anes-
thesia is listed in Table 2. There was no significant difference among the
anesthetic formulations.
Anesthesia of short duration is presented in Table 3. The 2% lido-
caine with 1:50,000 epinephrine formulation significantly decreased
anesthesia of short duration for the lateral incisor but not the first
molar. The 3% mepivacaine formulation had a significantly increased
incidence of anesthesia of short duration when compared with both
the lidocaine formulations. The incidence of pulpal anesthesia (80
readings across time) for the three anesthetic solutions is presented
in Figures 1 and 2.
Discussion
We based our use of the electric pulp test reading of 80, signaling
maximum output, as a criterion for pulpal anesthesia on the studies of
Dreven et al (23) and Certosimo and Archer (24). These studies (23,
24) showed that no patient response to an 80 reading ensured pulpal
anesthesia in vital, asymptomatic teeth. Additionally, Certosimo and
Archer (24) showed that electric pulp test readings of less than 80 re-
sulted in pain during operative procedures in asymptomatic teeth.
Therefore, using the electric pulp tester before beginning dental proce-
dures on asymptomatic, vital teeth will provide the clinician a reliable
indicator of pulpal anesthesia.
The success of the infiltration of 2% lidocaine with 1:100,000
epinephrine was 100% in the lateral incisor (Table 1). Various authors
(1–17) have evaluated the success of maxillary infiltrations using the
electric pulp tester. Generally, the results of these studies showed
successful anesthesia ranging from 62% to 100%. It is very difficult
to compare the results of the previous studies with the current study
because the authors used different dosages of anesthetic agents and
vasoconstrictors and evaluated different teeth. Nusstein et al (11), Gross
JOE — Volume 35, Number 9, September 2009
 CONSORT Randomized Clinical Trial
TABLE 2. The Onset of Pulpal Anesthesia (minutes,  standard error) 2 Lidocaine with 1:100,000 2 Lidocaine with 1:50,000
epinephrine epinephrine
2% 2% 3 Mepivacaine
lidocaine lidocaine
(1:100,000 (1:50,000 3% 100
epinephrine) epinephrine) mepivacaine

Percentage of 80 Readings
Lateral 3.9 (0.6) 3.1 (0.4) 2.6 (0.5)
incisor* 75
First molar* 5.1 (1.1) 4.3 (0.6) 4.0 (0.4)
n = 28 for the lateral incisor and n = 28 for the first molar.
50
*There were no significant differences (p < 0.05) among the solutions.

et al (13), Mikesell et al (14), Evans et al (15), and Scott et al (17) used 25

a similar methodology to the current study and showed an 85%, 97%,
97%, 62%, and 95% to 100% success rate, respectively, for the lateral
incisor with an infiltration of 1.8 mL of 2% lidocaine with 1:100,000 0
epinephrine. Regarding the first molar, the success rate was 97% 1 5 9 13 17 21 25 29 33 37 41 45 49 53 57

with the 2% lidocaine with 1:100,000 epinephrine (Table 2). Gross
et al (13), Mikesell et al (14), and Evans et al (15) used a similar meth-
odology to the current study and showed an 82%, 100%, and 72%
success rate, respectively, for the first molar with an infiltration of
1.8 mL of 2% lidocaine with 1:100,000 epinephrine. The success
rate for both the lateral incisor and first molar in the previous studies
(11, 13–15, 17) shows some variation that may relate to population or
operator differences. In general, the infiltration injection of 1.8 mL of
2% lidocaine with 1:100,000 epinephrine may not always be 100%
successful because of the individual variations in response to the
drug administered, operator differences, and variations of anatomy
as well as tooth position. For instance, previous investigations have
found varying success rates when using the same type and volume of
anesthetic (suggesting variations in response to the drug administered)
in studies designed with the same operator protocol (suggesting oper-
ator differences) and using patient populations that were similar in age
and sex. Also, some investigators have found differences in success by
tooth position such as lateral incisor versus the molar (13, 15).
The success rate of the 2% lidocaine with 1:50,000 epinephrine
formulation was 100% for the lateral incisor and 93% for the first molar
(Table 1). The success rate of the 3% mepivacaine formulation was 93%
for both the lateral incisor and first molar (Table 1). Because the defi-
nition of success did not include the duration of pulpal anesthesia, there
was no significant difference among the anesthetic solutions. Because
we studied a young adult population, the results of this study may not
apply to children or the elderly.
Time (Minutes)
Figure 1. The incidence of maxillary lateral incisor pulpal anesthesia as
determined by the lack of response to electrical pulp testing at the maximum
setting (percentage of 80 readings) at each postinjection time interval, for the
three anesthetic solutions.
Gross et al (13), Mikesell et al (14), Nusstein et al (11), Evans et al
(15), and Scott et al (17), using 1.8 mL of 2% lidocaine with
1:100,000 epinephrine, reported onset times for the lateral incisor of
2.5, 2.9, 5.1, 3.0, and 4.7 minutes, respectively. Except for Nusstein et
al (11) and Scott et al (17), the results are similar for the current study.
The differences between this study and the Nusstein (11) and Scott (17)
investigations are most likely attributable to differences in patient popu-
lations, although it is possible that operator differences may play a role.
In the first molar, the onset times ranged from 4.0 to 5.1 minutes with no
statistical differences among the three solutions (Table 2). Gross et al
(13), Mikesell et al (14), and Evans et al (15) using 1.8 mL of 2%
lidocaine with 1:100,000 epinephrine reported onset times for the first
molar of 4.3, 4.7, and 3.7 minutes, respectively. Other authors
(1–17) have reported onset times of 2 to 5 minutes for maxillary infil-
trations using lidocaine solutions. Increasing the epinephrine
2% Lidocaine with 1:100,000 2% Lidocaine with 1:50,000
epinephrine epinephrine
3% Mepivacaine

In the lateral incisor, the onset times ranged from 2.6 to 3.9 minutes 100
with no statistical differences among the three solutions (Table 2).
Percentage of 80 Readings

75
TABLE 3. Percentages and Number of Subjects who Experienced Short
Duration of Anesthesia
2% lidocaine 2% lidocaine 50
(1:100,000 (1:50,000 3%
epinephrine) epinephrine) Mepivacaine
Lateral 60 (18/30) 20 (6/30) 96 (27/28) 25
incisor
(%)*†‡
First 17 (5/29) 25 (7/28) 93 (26/28)
0
molar 1 5 9 13 17 21 25 29 33 37 41 45 49 53 57
(%)†‡
Time (Minutes)
Failures were excluded from the calculation of short duration of anesthesia.
*Significant difference between the 2% lidocaine with 1:100,000 epinephrine and 2% lidocaine with Figure 2. The incidence of maxillary first molar pulpal anesthesia as deter-
1:50,000 epinephrine. mined by the lack of response to electrical pulp testing at the maximum setting
†
Significant difference between the 2% lidocaine with 1:100,000 epinephrine and 3% mepivacaine. (percentage of 80 readings) at each postinjection time interval for the three
‡
Significant difference between the 2% lidocaine with 1:50,000 epinephrine and 3% mepivacaine. anesthetic solutions.

JOE — Volume 35, Number 9, September 2009 Comparison of 2% Lidocaine with Epinephrine and Mepivacaine for Maxillary Infiltrations 1175
CONSORT Randomized Clinical Trial
concentration to 1:50,000 epinephrine or using a plain solution of 3%
mepivacaine did not increase the onset of pulpal anesthesia. Therefore,
in general, onset times for maxillary infiltrations with these solutions
would range from 2 to 5 minutes (1–11, 13–15).
Figure 1 shows the decline of pulpal anesthesia over 60 minutes
for the lateral incisor. For the 2% lidocaine with 1:100,000 epinephrine
formulation, approximately 63% of the subjects had pulpal anesthesia at
45 minutes and only 33% at 60 minutes. Nusstein et al (11), Gross et al
(13), Mikesell et al (14), Evans et al (15), and Scott et al (17) also
showed similar declining rates of pulpal anesthesia when using 1.8
mL of 2% lidocaine with 1:100,000 epinephrine. The 2% lidocaine
with 1:50,000 epinephrine maintained a higher percentage of pulpal
anesthesia than the 1:100,000 epinephrine solution (Fig. 1). Approxi-
mately 97% of the subjects had pulpal anesthesia at 45 minutes and
almost 80% at 60 minutes. Anesthesia of short duration was significantly
decreased with the 2% lidocaine with 1:50,000 epinephrine formula-
tion (Table 3). Therefore, increasing the epinephrine concentration
to 1:50,000 increases the duration of pulpal anesthesia for the lateral
incisor. A previous study by Knoll-Köhler and Förtsch (6) has also
shown a higher epinephrine concentration increases the duration of
anesthesia in anterior teeth. Mikesell et al (14) showed a statistically
slower decline of pulpal anesthesia with a 3.6-mL volume of 2% lido-
caine with 1:100,000 epinephrine over 60 minutes for the lateral
incisor when compared with the 1.8-mL volume, with 72% of the
subjects having pulpal anesthesia at 45 minutes and 50% at 60 minutes.
In the current study, there was a higher percentage of subjects with
pulpal anesthesia at 45 and 60 minutes than recorded by Mikesell et
al (14). However, 2% lidocaine with 1:50,000 epinephrine did not
provide complete pulpal anesthesia for an hour. Scott et al (17) found
a repeated infiltration of 1.8 mL of 2% lidocaine with 1:100,000
epinephrine 30 minutes after an initial infiltration of the same dose
of anesthetic significantly improved the duration of pulpal anesthesia,
from 37 minutes through 90 minutes, in the maxillary lateral incisor.
They found 90% of the subjects had pulpal anesthesia at 60 minutes
for the repeated infiltration. Therefore, if pulpal anesthesia is required
for 60 minutes, an initial dose of 1.8 mL of 2% lidocaine with 1:50,000
epinephrine or repeating an infiltration at 30 minutes using 1.8 mL of
2% lidocaine with 1:100,000 epinephrine should both be reasonably
effective.
Figure 1 shows a significant decline in pulpal anesthesia with the
3% mepivacaine formulation in the lateral incisor. Approximately 73%
of the subjects had pulpal anesthesia at 20 minutes, 30% at 30 minutes,
and none at 47 minutes. Anesthesia of short duration was significantly
higher with the 3% mepivacaine formulation when compared with the
two lidocaine formulations (Table 3). Petersen et al (2) and Burns et al
(22) also showed a shorter duration of anesthesia for 3% mepivacaine
in the maxilla.
For the first molar, a slower decline of pulpal anesthesia was
shown for 2% lidocaine with 1:100,000 than in the lateral incisor
(Fig. 2). Gross et al (13), Mikesell et al (14), and Evans et al (15)
also showed a similar pattern of pulpal anesthesia of the first molar
when using 1.8 mL of 2% lidocaine with 1:100,000 epinephrine.
This difference in the decline of pulpal anesthesia may be attributed
to differences in maxillary anatomy in the lateral incisor versus molar
region. Differences in bone thickness, root approximation, and
vascular supply may play a role in anesthetic duration. Previous differ-
ences in anesthetic success between the lateral incisor and molar
region (13, 15) have also been attributed to maxillary anatomical
considerations. Anesthesia of short duration was not significantly
different between the two lidocaine formulations (Table 3). Therefore,
increasing the epinephrine concentration does not contribute signifi-
cantly to a longer duration of pulpal anesthesia in the first molar.
1176 Mason et al.
Recently, Mikesell et al (14) showed that increasing the amount of
lidocaine from 1.8 mL to 3.6 mL provided a longer duration of pulpal
anesthesia for the first molar. However, complete pulpal anesthesia
was not obtained for 60 minutes. In the current study, pulpal anes-
thesia started to decline for 2% lidocaine with 1:100,000 or
1:50,000 epinephrine after about 49 to 53 minutes (Fig. 2). It is
important to realize that if an hour of pulpal anesthesia is required
for the first molar, 1.8 mL of 2% lidocaine with either 1:100,000 or
1:50,000 epinephrine may not provide the necessary duration of
pulpal anesthesia.
Figure 2 shows a significant decline in pulpal anesthesia with the
3% mepivacaine formulation in the first molar. Approximately 73% of
the subjects had pulpal anesthesia at 20 minutes, 30% at 30 minutes,
and only 20% at 47 minutes. Anesthesia of short duration was signifi-
cantly higher with the 3% mepivacaine formulation when compared
with the two lidocaine formulations (Table 3).
Conclusions
The onset of pulpal anesthesia was not significantly different
between 2% lidocaine with either 1:100,000 or 1:50,000 epinephrine
and 3% mepivacaine for the lateral incisor and first molar. Anesthetic
success was not significantly different between 2% lidocaine with either
1:100,000 or 1:50,000 epinephrine and 3% mepivacaine for the lateral
incisor and first molar. Increasing the epinephrine concentration from
1:100,000 to 1:50,000 in a 2% lidocaine formulation significantly
decreased pulpal anesthesia of short duration for the lateral incisor
but not the first molar. For both the lateral incisor and first molar,
3% mepivacaine significantly increased pulpal anesthesia of short dura-
tion compared with 2% lidocaine with either 1:100,000 or 1:50,000
epinephrine.
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