PEDIATRIC DENTISTRY V 43 / NO 2 MAR / APR 21

RANDOMIZED CONTROL TRIAL

Double-Blind, Randomized Clinical Trial Comparing One Percent Buffered Versus Two
Percent Unbuffered Lidocaine Injections in Children
Suzanne D. Baker, DDS, MPH1 • Jessica Y. Lee, DDS, MPH, PhD2 • Raymond P. White, DDS, PhD3 • Leonard Collins4 • Wanda Bodnar, PhD5 •
Ceib Philips, MPH, PhD6 • Kimon Divaris, DDS, PhD7

Abstract: Purpose: Buffered local anesthetics offer an alternative to conventional, unbuffered anesthetic formulations; however, evidence about
their use in children is scant. The purpose of this study was to determine the anesthetic and physiologic differences associated with the use of
buffered one percent and unbuffered two percent lidocaine (both with 1:100,000 epinephrine) in children. Methods: In this randomized, double-
blinded, crossover study, 25 children ages 10 to 12 years old received two inferior alveolar never blocks, at least one week apart, randomized to alter-
nating sequences of two drug formulations: (1) formula A–three mL buffered one percent lidocaine (i.e., including 0.3 mL of 8.4 percent sodium
bicarbonate); or (2) formula B–three mL unbuffered two percent lidocaine. Primary outcomes were mean blood lidocaine levels (15 minutes post-
injection), timing of clinical signs onset, response to pain on injection, and duration of anesthesia. Analyses relied upon analysis of variance for
crossover study designs and a P<0.05 statistical significance criterion. Results: The buffered formulation resulted in significantly lower mean blood
lidocaine levels compared to unbuffered–a 63 percent (P<0.05) weight-adjusted relative decrease. The authors found no important differences in
pain upon injection, onset, and duration of anesthesia. Conclusion: The buffered local anesthetic formulation showed equal effectiveness with a
double-concentration unbuffered formulation while resulting in lower mean blood lidocaine levels–an important gain for the prevention of anes-
thetic toxicity. (Pediatr Dent 2021;43(2):88-94) Received April 25, 2020 | Last Revision December 7, 2020 | Accepted December 14, 2020
KEYWORDS: LOCAL ANESTHESIA, LIDOCAINE, PEDIATRIC DENTISTRY, BUFFERED ANESTHETIC, INFERIOR ALVEOLAR NERVE BLOCK

Pain control is of paramount importance for procedure success
and patient management in pediatric dentistry. Although ad-
juncts exist to aid in pain management during procedures,
including distraction, anxiolytic medications, and sedative drugs,
the primary tool for pain prevention and management remains
local anesthesia. Unfortunately, injecting local anesthetic can
be a particularly anxiety-producing procedure for patients of
all ages, especially young children.1,2 Minimizing pain and maxi-
mizing safety during the administration of local anesthetic must
be a goal of all clinicians, particularly those treating children.
New options for improving local anesthetic effectiveness
continue to emerge with a better understanding of their phar-
macology. The addition of a vasopressor, usually epinephrine, to
lidocaine and other injected local anesthetics serves to prolong
the anesthetic effect by reducing blood flow to the anatomic
area and the diffusion of the drug away from the anatomic site
1 Dr. Baker is in private practice and 4Mr. Collins is a research specialist, Molecular
Education, Technology and Research Center, at North Carolina State University, both in
in Raleigh, N.C., USA. 2Dr. Lee is a distinguished professor and chair, Division of
Pediatric and Public Health, and a professor, Department of and Health Policy and
Management, Gillings School of Public Health; 3Dr. White is a professor, Division of
Craniofacial and Surgical Care, Adams School of Dentistry; 5Dr. Bodnar is an assistant
professor, Department of Environmental Sciences and Engineering; 6Dr. Phillips is an
associate dean of Advanced Education/Graduate Studies, Division of Oral and Cranio-
facial Health Sciences; and 7Dr. Divaris is a professor, Division of Pediatric and Public
Health, Adams School of Dentistry, all at the University of North Carolina at Chapel
Hill, Chapel Hill, N.C., USA.
Correspond with Dr. Lee at Jessica_Lee@unc.ed
HOW TO CITE:
Baker SD, Lee JY, White RP, et al. Double-blind, randomized clinical trial
comparing one percent buffered versus two percent unbuffered
lidocaine injections in children. Pediatr Dent 2021;43(2):88-94.
of injection. To prolong the shelf life of the vasopressor, the
drug combination must be formulated with a low pH: approxi-
mately pH 3.5 for lidocaine (1:100,000 epinephrine). When
injected, the low pH causes the sting felt by patients on injec-
tion. Several studies have demonstrated that buffering local
anesthetics just before use can produce positive outcomes, in-
cluding less sting on injection, faster onset of the drug, and
possibly added drug potency (i.e., providing the same positive
clinical effect at a lower dosage).3-8 The buffered drug injected
at a neutral pH reduces the time-lag required for buffering by
tissue fluid while retaining the desired qualities of the vaso-
pressor. The clinical outcome is a more rapid onset of the local
anesthetic effect.6,7
The ability to potentially decrease the required dose of a
local anesthetic drug while maintaining an equal anesthetic
effect has important implications for pediatric dentistry, as
children may be at greater risk for toxicity related to these
drugs.9 Although there is a lack of centrally reported data on
adverse events in dentistry for children, including local anes-
thetic toxicity, one recent study reviewed National Poison Data
System data and discovered that between the years of 2004 and
2018, for children 12 years old and younger, there were 27 cases
of local anesthetic toxicity reported in a dental setting.10 The
affected children’s average age was 6.8 years, and the most
frequent outcome was seizure activity following the administra-
tion of local anesthesia.
The benefits of buffered local anesthetic have not been
replicated and validated among pediatric populations. Chopra
et al. found no reduction in pain on injection or reduction in
time to onset of anesthesia for inferior alveolar nerve (IAN)
block using buffered versus unbuffered two percent lidocaine
(with 1:100,000 epinephrine) in children ages six to 12 years.11
That investigation utilized gingival probing to assess soft tissue
anesthesia, with parents reporting pain sensation based on

88 BUFFERED VS. UNBUFFERED LIDOCAINE IN CHILDREN

 PEDIATRIC DENTISTRY V 43 / NO 2 MAR / APR 21

observation of their children. Although pulpal anesthesia was presented in Figure 1. Analyses were conducted among the
not tested, dental treatment was performed following injection. 25 participants who completed the trial.
Another recent study comparing two percent buffered Randomization was performed for the type of drug given
versus two percent nonbuffered lidocaine found no difference first using a computer-generated random sequence for the first
in pain on injection or in time to onset of numbness between 24 participants. The randomization of the additional two parti-
the two formulations.12 Importantly, neither investigation mea- cipants was determined with a coin toss. During the first
sured blood lidocaine levels, which is a key objective physiologic session, each subject received a left IAN block with the first ran-
measure with relevance to anesthetic toxicity. Moreover, both domly assigned anesthetic using the Halstead technique. At
investigations studied two percent lidocaine formulations, least a week later, which was substantially longer than the 1.5-
whereas understanding whether lower lidocaine concentrations to two-hour elimination half-life of lidocaine, local anesthetic
are equally effective with the standard two percent when buffered injections were administered using the alternate local anes-
is an important, practical clinical question. To address this thetic. All injections were on the left side of the mouth to
knowledge gap and contribute to the evidence base on safety control for any variation in anatomy within individual subjects
and efficacy of local anesthesia in pediatric dentistry, this inves- and to control for variability in the technique of administration
tigation sought to compare the anesthetic effects of buffered of right versus left IAN block injections. Immediately prior
one percent lidocaine with those of unbuffered two percent to injection, the tissue was dried using a two by two gauze and
(both with 1:100,000 epinephrine). a topical anesthetic (LolliCaine, 20 percent benzocaine gel,
The purposes of this double-blind, randomized clinical trial Centrix, Shelton, CT) was placed on the site of injection for 30
were, for the first time in a pediatric dental setting, to: (1) com- seconds, with excess removed before injection. The administered
pare mean blood lidocaine levels between standardized injec- formulations were three mL of buffered one percent lidocaine
tions of buffered one percent and unbuffered two percent with 1:100,000 epinephrine or three mL nonbuffered of two
lidocaine (both with 1:100,000 epinephrine) in a pediatric percent lidocaine with 1:100,000 epinephrine. Buffering was
population; (2) compare self-reported pain on injection for each done using the Anutra system (Anutra Medical, Inc., Morrisville,
formulation; and (3) compare anesthetic characteristics between N.C., USA), a sterile and closed anesthetic delivery system in
the two formulations, including the time of onset as well as the which each mL of solution is individually buffered as it is
duration of numbness. drawn into a syringe, minimizing the risk for human error in
compounding the local anesthetic chairside.
Methods The total volume of the buffered formulation included 0.3
Study design and population. This double-blinded, random- mL of 8.4 percent sodium bicarbonate; thus 27 mg of lidocaine
ized clinical trial employed a crossover study design
(i.e., participants served as their own controls in alter-
nating sequences). It was approved by the Institutional
Review Board (IRB) of the UNC-Chapel Hill
(#16-3106) and registered as a randomized clinical trial
(NCT #03562481). Inclusion criteria at the time of en-
rollment included: 10 to 12 years old; healthy (ASA I);
body weight within the interquartile range (IQR) for
this age group as defined by the Centers for Disease
Control and Prevention (IQR equals 33 to 60 kg);
English-speaking and reading (subject and parent); will-
ingness to participate in two sessions; no history of
adverse reaction to dental anesthetic; and permanent
mandibular left first molar present and without a clin-
ically visible carious lesion. Subjects were excluded if they
had: an allergy to lidocaine anesthetic drugs; a local
anesthetic drug administered within the week before the
session in which they participated; or symptomatic teeth
or oral mucosa (i.e., pain in their mouth).
The authors enrolled 26 subjects, a sample size that
was estimated to provide adequate power based on data
from similar investigations among young, healthy adults
and which was within the authors’ budgetary limits.8,13
Eligible subjects were enrolled after obtaining verbal
and written informed assent as well as verbal and written
informed consent from their caregivers, as directed by the
IRB. Both children and caregivers were provided with in-
centives for participating in the study. Following session
one, each child and each caregiver were offered a $30 gift
card; following session two, which completed the study,
each child was offered two $30 gift cards and each care-
giver was offered one $30 gift card. A CONSORT (http:
//www.consort-statement.org/) flow diagram of subject Figure 1. CONSORT flow diagram illustrating the study participants’ recruitment, enroll-
recruitment, enrollment, randomization, and analysis is ment, randomization, and analysis.

BUFFERED VS. UNBUFFERED LIDOCAINE IN CHILDREN 89

PEDIATRIC DENTISTRY V 43 / NO 2 MAR / APR 21
was included in the buffered formulation compared to 60 mg
in the unbuffered formulation. A standard 27-gauge, 30-mm
long needle was utilized. A single clinician (the study’s cor-
responding author) administered all injections to minimize
variation, including injection speed. No additional modifiers
were in place to control the rate of injection, but the same
conditions were applied to all clinical sessions and the clinician
was blinded regarding the drug injected.
Data and specimen collection. Subjects’ vital signs were
recorded before lidocaine injection, just before the blood draw,
30 minutes after the blood draw, and prior to discharge. Both
study staff and subjects were masked regarding the formula-
tion (i.e., buffered or nonbuffered) of the injected drugs. The
following were recorded in each subject’s clinical station: (1)
response to pain on injection self-reported immediately follow-
ing a 10-point scale anchored (one equals “no pain” and 10
equals “worst pain imaginable,” recorded by the clinician per-
forming the IAN block); (2) self-reported response in minutes
from time of injection to time the lower lip became numb;
(3) response (yes/no) to cold test (Endo ice) on the ipsilateral
permanent mandibular first molar before injection and after
drug injection at 30-minute intervals through 120 minutes (a
subject’s response was considered “no” if they did not report
feeling a sensation for up to 15 seconds of contact with the
tooth); participants who provided a negative pulpal sensibility
response at baseline (i.e., prior to injection) were excluded from
subsequent analysis of this outcome; (4) response in minutes
to the time the lower lip was no longer numb up to 120 min-
utes; a fresh, single size one cotton pellet was used on the
occlusal two-thirds of the buccal surface of the permanent left
first molar at each time point, and a Frankl score (one to four)
was recorded at the time of injection.
A certified clinical trial nurse applied topical anesthetic
cream (EMLA Cream, a eutectic mixture of lidocaine 2.5% and
prilocaine 2.5%) to the antecubital fossa of the upper extrem-
ity 30 minutes prior to the blood draw. Fifteen minutes after
local anesthetic injection, the cream was wiped completely from
the skin using a gauze pad and 10 mL venous blood was ob-
tained.14 To ensure the collection of sufficient serum for analysis,
whole blood was collected from each patient into two vacutainer
tubes. Tubes were inverted three times and placed on ice 30
minutes following collection. Within two hours of collection,
Table 1. DEMOGRAPHIC INFORMATION
ABOUT THE 25 STUDY PARTICIPANTS
n %
Gender
Male 13 52
Female 12 48
Race
Black 4 16
Asian 1 4
White 19 76
Other 1 4
Age (years)
10 6 24
11 10 40
12 9 36
90 BUFFERED VS. UNBUFFERED LIDOCAINE IN CHILDREN
sample tubes were centrifuged at 1000 g for 15 minutes at four
degrees Centigrade to separate serum. Serum from both tubes
was combined in a secondary polypropylene tube and vortex
mixed to provide one serum sample of at least three mL or
more per patient.
Serum was then transferred to cryovials in 0.5 mL aliquots
and stored at -80 degrees Centigrade until assayed. Stable
isotope-labeled D10-lidocaine hydrochloride was used as the
internal standard. Lidocaine levels were quantified using a
Waters ACQUITY UPLC system (Waters Corp., Milford, Mass.,
USA) coupled to a Thermo TSQ Quantum Ultra triple-
quadrupole mass spectrometer (Thermo Fisher Scientific,
Waltham, Mass., USA). Raw data were processed with Xcalibur
3.0 software (Thermo Scientific, Waltham, Mass., USA).
Analytical approach. The study’s outcome variables in-
cluded: response to pain on injection; timed onset of clinical
signs (when subjects’ lower lips were numb and no longer
numb); binary response to pulpal anesthesia; and mean blood
lidocaine levels (15 minutes following injection). The interven-
tion (primary explanatory variable) was the alternate local anes-
thetic formulation. Scannable data collection forms and
questionnaires for clinical data were used via the Teleform system
for direct export into a Microsoft Access database (Microsoft
Corp., Redmond, Wash., USA), similar to previous studies. 8,11
Coded hardcopy case report forms were kept in a secure loca-
tion. Completed forms were digitized. Logical and quality
control checks were implemented using custom-written software
scripts.
Descriptive statistics, plots, and bivariate association tests
were used for data summarization and analysis. Nonparametric
tests (i.e., median and tests of symmetry and marginal homo-
geneity) were used to conduct initial contrasts of categorical and
interval subjective measures of anesthetic effectiveness between
drugs. Similarly, t-tests were used to contrast serum lidocaine
concentrations. Analyses of variance to determine drug differ-
ences in serum lidocaine concentration, pain upon injection,
and lip sign, accounting for the cross-over study design (i.e.,
period and sequence effects), were implemented using Stata 15.1
software (StataCorp LP, College Station, Texas, USA) using a
P<0.05 statistical significance criterion.
Results
The demographic characteristics of the analytical study sample
are presented in Table 1. Of note, no participants experienced
significant adverse events (defined as undesirable experiences
or outcomes that might jeopardize the patient or require med-
ical intervention) as a result of this study.
Blood lidocaine level (serum concentration). A signifi-
cant difference was detected between buffered and nonbuffered
drug formulations (P= 0.001) in the mean blood lidocaine
levels–a 63 percent relative decrease in blood lidocaine concen-
tration (ng/mL) at 15 minutes following injection for the buf-
fered formulation (Figure 2). The median blood lidocaine level
for the buffered drug was 230 ng/mL (range equals 88 to 762
ng/mL) and 534 ng/mL (interquartile range equals 243 to
2,836 ng/mL) for the nonbuffered drug. Mean blood lidocaine
levels for the buffered drug were 244 ng/mL and 600 ng/mL
for the nonbuffered drug.
Time to lip sign (onset of soft tissue numbness). No sig-
nificant difference was detected between buffered and non-
buffered drug formulations in time to onset of soft tissue
numbness (Table 2). The mean time for anesthesia onset was
one minute less for the buffered drug (i.e., 3.4 minutes
 PEDIATRIC DENTISTRY V 43 / NO 2 MAR / APR 21

versus 4.4 minutes for the nonbuffered drug). The median
time to onset of soft tissue anesthesia was three minutes for
both drugs.
Time to lip not numb (duration of soft tissue anesthesia).
No significant difference was detected between buffered and
nonbuffered drug formulations in time for the lower lip to no
longer be numb (Table 2). The mean duration of soft tissue
anesthesia tended to be longer for the nonbuffered drug (241
minutes ±91 minutes [standard deviation]) than the nonbuf-
fered drug (218 minutes ±60 minutes [standard deviation]).
Median times were virtually identical.
Pain upon injection. No significant difference was detec-
ted between buffered and nonbuffered drug formulations for
pain on injection (Table 2). Median reported pain levels for
both drugs were three on a scale ranging from zero to 10.
Duration of pulpal anesthesia. The duration of pulpal
anesthesia was measured as time to first positive response
(“yes”to feeling sensation) to Endo Ice on the permanent man-
dibular first molar. Seven participants were excluded from this
analysis due to testing negative (“no” to feeling sensation) at
baseline (i.e., preinjection). Two additional participants were
excluded due to having missing data at follow-up. Among the
16 participants included in this analysis, there was no signifi-
cant difference in the duration of pulpal anesthesia (P=0.09);
however, the duration of anesthesia tended to be longer with
the unbuffered anesthetic (Table 3).

Discussion
This study compared the anesthetic effects of buffered versus
unbuffered lidocaine for IAN block anesthesia among children
and adds to the evidence base of pediatric local anesthesia safety
and efficacy. The results presented here support that one per-
cent buffered lidocaine had the same anesthetic effects when
compared to two percent nonbuffered lidocaine, both with
1:100,000 epinephrine, and was associated with substantially
lower blood serum lidocaine levels. This novel information
addresses an existing knowledge gap regarding the use of buf-
fered local anesthetics in children and contributes to a growing
body of literature supporting the use of buffered formula-
tions as favorable alternatives to unbuffered ones.
In an earlier study by Chopra et al., no difference in time
of soft tissue onset of numbness was found between two percent
buffered and nonbuffered solutions using gingival probing as
a proxy for soft tissue anesthesia,10 as opposed to self-reported
of onset of lower lip numbness, which was used in the current
study. Other studies in adult populations report a faster onset of
numbness when using buffered lidocaine solutions versus non-
buffered solutions. Malamed et al. reported an average onset of
Figure 2. Mean blood lidocaine concentrations 15 minutes following anesthesia of under two minutes for alkalinized compared to
injection. The use of one percent buffered lidocaine resulted in a 63 over six minutes for onset with a nonalkalinized solution.15
percent relative decrease in mean blood lidocaine concentration as com-
pared to two percent nonbuffered lidocaine (P=0.001). The top and
bottom edges of each box represent the 75th and 25th percentiles of
the distribution, and the horizontal line within each box marks the
Table 3. DISTRIBUTION OF PULPAL ANESTHESIA DURATION
distribution median. The whiskers indicate the limits of the theoretical
distribution, defined as 1.5 times the interquartile range, and the dots (NEGATIVE PULPAL SENSIBILITY, COLD TEST) AMONG
illustrate the three outlying high observations. THE 25 STUDY PARTICIPANTS, ACCORDING TO
BUFFERED AND NONBUFFERED ANESTHETIC DRUG*†
Table 2. DISTRIBUTION OF SUBJECTIVE MEASURES OF Nonbuffered
ANESTHESIA AMONG THE 25 STUDY PARTICIPANTS, 30 60 minutes 90 ≥120
ACCORDING TO DRUG minutes minutes minutes
Buffered Nonbuffered P-value* 30 minutes 4 1 0 2
Median (range) 3 (2-7) 3 (0-18) 0.73 60 minutes 0 0 1 1
Time to “lip
Buffered 90 minutes 1 0 0 1
sign” (minutes) Mean±(SD)† 3.4±1.3 4.4±3.7 0.22
≥120 minutes 0 0 0 5
Time to “lip not Median (range) 212 (113-369) 210 (149-516) 0.32
numb” (minutes) Mean±(SD) 218±60 241±91 0.17 * Test of trend and symmetry for individuals receiving both formulations
(i.e., cross-over design), P=0.09; there was no statistically significant differ-
Pain upon Median (range) 3 (1-9) 3 (1-7) 0.29 ence between the two groups, but the duration of anesthesia tended to be
injection (10- longer among participants receiving the nonbuffered anesthetic formulation.
point scale score) Mean±(SD) 3±1.9 3.3±1.5 0.38
† Seven participants were excluded due to negative baseline (preinjection)
pulpal sensibility (cold) test and two participants were excluded due to
* P-values were derived from median tests for comparison of median values and missing data (i.e., one participant had missing pulpal sensibility testing
analyses of variance accounting for the crossover design for mean values. data at 90 minutes and another participant had missing pulpal sensibility
† SD=standard deviation. testing data at 120 minutes).

BUFFERED VS. UNBUFFERED LIDOCAINE IN CHILDREN 91

PEDIATRIC DENTISTRY V 43 / NO 2 MAR / APR 21
Kashyap6 and Phero8 corroborated these findings but with a less
dramatic difference between alkalinized and nonalkalinized
formulations. A 2018 meta-analysis by Guo et al. concluded
that buffering local anesthetics before IAN block anesthesia
could result in a faster onset of numbness by about one minute.16
The results generated in this investigation have limitations.
First, the sample size was small and, as it was estimated based
on similar previously reported trials conducted in adults, it was
not based on a formal sample size estimation. Consequently,
despite the finding of significantly lower lidocaine concentration
associated with the one percent buffered lidocaine formulation,
the authors may have been underpowered to detect significant
differences in other outcomes. Data were obtained from chil-
dren from a limited age range, subjects who were perhaps older
than patients who might benefit the most from buffered local
anesthetics administered at lower dosages. Subjective anesthetic
effectiveness data may be subject to different forms of bias;
however, this is an unavoidable consequence of measuring
sensations such as pain and numbness. The authors used lip
sign and thermal sensibility testing as proxies for clinical effective-
ness, as no restorative treatment was completed during sessions.
This was intentional to minimize the potential confounding
events of restorative appointments. In future studies, the in-
clusion of a preoperative assessment of fear or anxiety would
be valuable. Cold stimulation of molars, stimulating widely
distributed C-fibers and A-delta fibers in the dental pulp, is a
proxy for adequate anesthesia for dental procedures. Seven
participants tested negative in this pulpal sensibility assessment
at baseline (i.e., preinjection), and two additional participants
had incomplete data, resulting in a substantial reduction of the
effective sample size used for the study of this outcome.
Additional data on the effectiveness of buffered local anes-
thetic drugs for a range of interventions in pediatric dentistry
are needed to confirm the findings reported here. For example,
the authors do not know if similar results would be obtained
with higher or lower dosages of buffered local anesthetics. The
administered three mL per injection in the present study is
1.3 mL greater than the typical volume administered per IAN
block but still within a clinically acceptable range. Although
this study demonstrated the anesthetic equivalence of buffered
one percent with nonbuffered two percent lidocaine formu-
lation, it did not provide evidence of anesthetic efficacy of
one percent buffered lidocaine in lower administered volumes.
Future studies should investigate its efficacy in volumes typically
used in daily practice (e.g., one 1.7 mL cartridge) and possibly
compare additional formulations of interest (e.g., one percent
buffered versus one percent nonbuffered lidocaine).
There has been a heightened interest in the dental literature
regarding the duration of lip numbness with the investigation
of phentolamine mesylate (PM).17 In the present study, numb-
ness for both drug formulations had a duration of at least 120
minutes, and no prolonged numbness beyond 24 hours was
observed. Standard postoperative instructions to caregivers of
children undergoing dental procedures in the mandibular arch
include numbness precautions, requiring parental supervision
to prevent soft tissue injury.18 Average soft tissue anesthesia for
mandibular block injections is reported to be approximately
190 minutes. Recent studies investigating duration of numbness
with and without the use of PM indicate that, when using 0.5
to one standard carpule of two percent lidocaine 1:100,000
epinephrine, lip numbness can be expected to last up to 135
minutes. 17 With PM, this duration of numbness is reduced
to 60 minutes, which may not be clinically relevant in young
92 BUFFERED VS. UNBUFFERED LIDOCAINE IN CHILDREN
children.15 However, these studies included children presenting
for dental treatment that needed to be completed and from a
very wide age range without a standard dosage of anesthetic
drug given. As PM is a vasodilator, it results in the rapid up-
take of lidocaine into the bloodstream, an effect that is not
advisable in a pediatric population at increased risk for adverse
outcomes, including lowering the seizure threshold, particularly
if used alongside other sedative medications.
Pulpal anesthesia tended to have a longer duration in indi-
viduals anesthetized using the nonbuffered anesthetic formu-
lation. However, the nonbuffered formulation was twice as
concentrated as the buffered formulation, and this difference
was not significant. The present study did not find a significant
difference in duration of pulpal anesthesia; however, there was
a trend for longer anesthesia duration associated with the non-
buffered formulation. The authors acknowledge that thermal
testing is of limited value in children with immature permanent
teeth and false negatives are common to both thermal testing
and electric pulp test in these cases.19 The authors believe the
10- to 12-year-olds who comprise this study’s population are
reliable reporters of sensation, yet a third of individuals in the
present study were excluded from this outcome analysis due to
a negative response to cold at baseline.
While demonstrating substantially lower blood serum lido-
caine levels, the present study showed no difference in pain on
injection for buffered versus nonbuffered local anesthetic in a
pediatric population for mandibular IAN block anesthesia. This
is consistent with Chopra et al., who reported no difference in
pain during IAN block anesthesia using the visual analog
scale (VAS) or the sound, eye, and motor scale.11 This is also in
agreement with Meincken et al., who reported no difference in
pain on injection in addition to no difference in time of onset
of numbness following injection.12 The adult dental literature,
including a recent meta-analysis, suggests that buffered lido-
caine significantly reduces injection pain (using VAS) compared
to nonbuffered lidocaine in IAN block anesthesia.16 This anal-
ysis rated existing evidence as low and noted the heterogeneity
of the analyses and small sample sizes included in the available
literature. The median pain rating in the present study was
three out of a possible 10, with individuals consistent between
their two sessions. Using a profound topical anesthetic and
injecting at a slow and steady speed both also mitigate pain
experienced during needle penetration and deposition of anes-
thetic into soft tissues. Fear may be a predictor of the pain
experience, but the present study did not measure dental anxiety
or fear.
Importantly, the authors found a 63 percent decrease in
mean blood serum lidocaine concentrations when using one
percent buffered anesthetic as opposed to two percent non-
buffered. This is expected, given the differences in concentra-
tion of this study’s buffered and nonbuffered formulations, but
these measurements are meaningful to consider in the context
of safety. This is the first study to examine blood lidocaine con-
centrations in a pediatric dental population using standardized
dosing. The American Academy of Pediatric Dentistry recom-
mends calculating a maximum anesthesia dose prior to any
restorative procedures in order to maximize patient safety by
minimizing the risk for overdose.18 Signs of toxicity including
central nervous system and cardiovascular events can begin to
be seen at a serum concentration of 6,000 ng/mL.20 Although
the present study’s mean, median, and range for both drug
formulations fell well below 6,000 ng/mL, it is important to
note that the one outlier in the unbuffered group had a serum

concentration of 2,800 ng/mL, which may be due to intravas-
cular deposition of the drug. One study assessing intravenous
entrance of a needle during 359 IAN blocks via positive aspira-
tions found that intravenous entrance occurred 15 percent of
the time, regardless of the side of injection.21
There is a paucity of information regarding blood lidocaine
levels in children following intraoral injections. A 1998 study
by Jurevic et al. analyzed blood samples taken from 12 children
who were under intravenous sedation for dental treatment. In
that study, children’s ages ranged between 4.5 and 12.5 years.22
Following intraoral injections of local anesthetic ranging from
48 mg to 180 mg, blood samples were taken at five, 10, 15, and
30 minutes, resulting in concentrations ranging from 500 to
3,800 ng/mL. This study had a small sample size of 12, a large
age range, and a wide drug dose range and involved the
placement of EMLA cream (a potent cutaneous topical cream)
for 90 minutes before intravenous access.22 Because it is likely
that not every clinician aspirates prior to injecting, The present
study’s findings should be taken as a warning of the possibility
of an increase in blood lidocaine concentration in the presence
of intravenous deposition. This reemphasizes the importance of
respecting the weight-based dose limits for children.
Despite its limitations, this study has strengths inherent to
the design. This study was double-blinded and used a crossover
design that controls for much of the possible variation in sub-
jective and objective measures. The authors maintained strict
enrollment and exclusion criteria (e.g., age range, disease-free),
which may limit this study’s generalizability but were needed
to ensure internal validity. In sum, the authors found and re-
ported clinical advantages to administering buffered local anes-
thetic drugs to pediatric dental patients: lower blood lidocaine
levels with lower drug dosages, similar responses to cold testing
for pulpal anesthesia, and no delay in recovery of sensation.
Particularly, the authors find this salient for children at higher
risk for adverse outcomes, including those who are very young,
those with liver disease or dysfunction, and children who are
sedated; when using buffered lidocaine for intraoral injections
in children, less drug is needed to achieve comparable clinical
outcomes.
Conclusions
Based on this study’s results, the following conclusions can
be made:
1. Three mL total volume of buffered and unbuffered
lidocaine is safe for use in inferior alveolar nerve
blocks in children when using the appropriate tech-
nique, including aspiration before injection.
2. A buffered one percent solution resulted in a mean
blood lidocaine level 63 percent lower than for a
nonbuffered two percent solution.
3. There were no significant differences in duration of
presumed pulpal and soft tissue anesthesia up to 120
minutes.
4. There were no differences in self-reported pain on
injection between the two formulations.
Acknowledgments
The authors would like to thank Cindy Marsh, RN, who took
all blood samples, as well as the many individuals who volun-
teered to help make this study possible, including undergrad-
uates, dental students, and dental residents at the University
of North Carolina-Chapel Hill, Adams School of Dentistry.
PEDIATRIC DENTISTRY V 43 / NO 2 MAR / APR 21
Funding for this study was provided by the Sunstar/American
Academy of Pediatric Dentistry postgraduate research fellow-
ship, UNC School of Dentistry MS Research Support Award,
and UNC Pediatric Dentistry.
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