Anesthesia, Local, Pain
Conditions
Keywords
Healthy pediatric volunteers
Brief summary
Local anesthesia is an integral part of clinical pediatric dental practice, but it has challenges. It can be uncomfortable for children, and the risk of adverse events limits how much is used. Some evidence suggests benefits of buffering local anesthetics including equal effect with less pain on injection. These findings have not been replicated and validated among pediatric populations, creating a gap in the knowledge base. To address this knowledge gap and contribute to the evidence base on safety and efficacy of local anesthesia in pediatric dentistry, this investigation proposes to compare the anesthetic effects of buffered 1% lidocaine with those of unbuffered 2%, among children. The specific aims of this investigation are to determine differences between buffered 1% and unbuffered 2% lidocaine (both with 1:100,000 epinephrine) used for inferior alveolar nerve block (IAN) anesthesia, in the following domains: 1. Pain experience on injection, time to onset following the administration, and time to recovery \[subjective\] 2. Blood lidocaine levels 15 minutes following the administration and duration of pulpal anesthesia \[objective\] Null Hypotheses: 1. No difference exists in anesthetic effectiveness for pulpal anesthesia after intraoral IAN block between buffered 1% Lidocaine with 1:100,000 epinephrine as compared to unbuffered 2% Lidocaine with 1:100,000 epinephrine. 2. No differences exist in peak blood lidocaine levels, pain on injection, time to lip numbness, and duration of anesthesia between the two drug formulations. Randomized subjects will be injected orally for bottom jaw anesthesia, with 3cc of buffered 1% lidocaine (30mg) 1:100,000 epinephrine or 3cc unbuffered of 2% lidocaine (60mg) 1:100,000 epinephrine. The injectable volume of the buffered formulation will include 0.3cc of 8.4% sodium bicarbonate. One faculty member in the Department of Pediatric Dentistry at the University of North Carolina (UNC) School of Dentistry will administer the drugs in the Pediatric Dentistry clinic. The same clinician will administer injection to the same subjects at both visits. Clinicians and subjects will not know which drug formulation is given at which appointment. A clinician will measure the level of discomfort on injection, how long it takes for the lip to be numb, how long it takes for the first molar tooth in that area to be numb, how long it takes the local anesthetic to wear off, and how much of the anesthetic is in the blood.
Interventions
DRUG1% Buffered Lidocaine 1:100,000 Epinephrine
A single IAN block with 3cc 1% Buffered Lidocaine (30mg) 1:100,000 Epinephrine using the Halstead technique.
DRUG2% Unbuffered Lidocaine 1:100,000 Epinephrine
A single IAN block with 3cc 2% Unbuffered Lidocaine (60mg) 1:100,000 Epinephrine using the Halstead technique.
Sponsors
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Intervention model description
Study subjects will serve as their own controls in this crossover AB/BA study design which is uniform within sequences (groups, i.e. AB/BA, of order of drug formulation administration), uniform within periods (equal time between administration of alternating drug formulations), and balanced (equal number of subjects within each study arm). The randomization will be performed to the type of drug given first, using a balanced randomization (half subjects buffered, half unbuffered) implemented with SAS software routines. During the first session, each subject will receive an IAN block with the first randomly assigned anesthetic formulation using the Halstead technique. At least a week later, substantially longer than the elimination half-life of the drug lidocaine (1.5-2hr), local anesthetic injections will be done using the alternate local anesthetic formulation.
Eligibility
Sex/Gender
ALL
Age
10 Years to 12 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 10-12 years * American Society of Anesthesiologists (ASA) Class I (Healthy) * Body Weight: the Interquartile Range (IQR) 33-60Kg for subject ages * Have ability to speak and read English * Willingness to participate in two sessions * No history of adverse reaction to dental anesthetic * Have bilateral, disease/symptom-free mandibular first molars present
Exclusion criteria
* Allergy to lidocaine class of anesthetic drugs * Local anesthetic drug use in past week * Current symptomatic teeth or oral mucosa * ASA II or above (including asthma)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Serum Lidocaine Concentration at 15 Minutes Post Injection | One blood draw taken 15 minutes following injection | Blood Lidocaine Level (mcg/mL) as measured in 10cc venous blood, taken 15 minutes following injection. Blood assayed for serum lidocaine levels with a Sciex TripleTOF liquid chromatography- mass spectrometry (LC-MS) equipped with a C18 Hypersil (10mm x 2.1mm, 3.0μm). |
| Mean Pain Scores Following Injection | Within 10 minutes of injection | Perceived pain on injection, self-reported verbally using a Likert scale from 1-10, with lower numbers corresponding to less pain (1 = no pain, 10 = worst pain imaginable). Lower scores reflect a lesser degree of pain. |
| Mean Time to Lower Lip Numbness Following Injection | Up to 30 minutes following injection | Time in minutes beginning immediately following injection to patient-reported lip numbness |
| Mean Time to Baseline Lip Sensation | Within 24 hours following injection | Response in minutes from injection to when lip is no longer numb, as self reported by patient. |
| Number of Participants Who Respond to Cold Stimulus (Positive/Negative) Prior to Injection | 5 minutes prior to injection | Response to experiencing sensation to cold stimulus on permanent molar tooth prior to injection |
| Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 30 Minutes Following Injection | 30 minutes following injection | Response to experiencing sensation to cold stimulus on permanent molar tooth 30 minutes following injection |
| Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 60 Minutes Following Injection | 60 minutes following injection | Response to experiencing sensation to cold stimulus on permanent molar tooth 60 minutes following injection |
| Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 90 Minutes Following Injection | 90 minutes following injection | Response to experiencing sensation to cold stimulus on permanent molar tooth 90 minutes following injection |
| Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 120 Minutes Following Injection | 120 minutes following injection | Response to experiencing sensation to cold stimulus on permanent molar tooth 120 minutes following injection |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1: Unbuffered Anesthetic, Then Buffered Anesthetic Subjects randomized to Unbuffered Anesthetic, then Buffered Anesthetic will first receive an injection with 2% Unbuffered Lidocaine 1:100,000 Epinephrine. After one week minimum washout period, subjects will then receive an injection with 1% Buffered Lidocaine 1:100,000 Epinephrine. | 12 |
| Sequence 2: Buffered Anesthetic, Then Unbuffered Anesthetic Subjects randomized to Buffered Anesthetic, then Unbuffered Anesthetic will first receive an injection with 1% Buffered Lidocaine 1:100,000 Epinephrine. After one week minimum washout period, subjects will then receive an injection with 2% Unbuffered Lidocaine 1:100,000 Epinephrine. | 14 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Sequence 1: Unbuffered Anesthetic, Then Buffered Anesthetic | Sequence 2: Buffered Anesthetic, Then Unbuffered Anesthetic | Total |
|---|---|---|---|
| Age, Continuous | 11.5 years STANDARD_DEVIATION 0.5 | 10.9 years STANDARD_DEVIATION 0.9 | 11.2 years STANDARD_DEVIATION 0.8 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 12 Participants | 19 Participants |
| Region of Enrollment United States | 12 Participants | 14 Participants | 26 Participants |
| Response to Cold Testing Negative Response to Cold Testing at Baseline | 2 Participants | 4 Participants | 6 Participants |
| Response to Cold Testing Positive Response to Cold Testing at Baseline | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 13 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 26 |
| other Total, other adverse events | 0 / 25 | 0 / 26 |
| serious Total, serious adverse events | 0 / 25 | 0 / 26 |
Outcome results
Primary
Average Serum Lidocaine Concentration at 15 Minutes Post Injection
Blood Lidocaine Level (mcg/mL) as measured in 10cc venous blood, taken 15 minutes following injection. Blood assayed for serum lidocaine levels with a Sciex TripleTOF liquid chromatography- mass spectrometry (LC-MS) equipped with a C18 Hypersil (10mm x 2.1mm, 3.0μm).
Time frame: One blood draw taken 15 minutes following injection
Population: One participant did not complete the second intervention and was excluded from the data analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buffered Anesthetic | Average Serum Lidocaine Concentration at 15 Minutes Post Injection | 243.5 mcg/ml | Standard Deviation 127.9 |
| Unbuffered Anesthetic | Average Serum Lidocaine Concentration at 15 Minutes Post Injection | 600.2 mcg/ml | Standard Deviation 497 |
Comparison: Analysis of variance for 2x2 crossover study using the pkcross routine of Stata 16.1 adjusting for perio and sequence effects.p-value: 0.003ANOVA
Primary
Mean Pain Scores Following Injection
Perceived pain on injection, self-reported verbally using a Likert scale from 1-10, with lower numbers corresponding to less pain (1 = no pain, 10 = worst pain imaginable). Lower scores reflect a lesser degree of pain.
Time frame: Within 10 minutes of injection
Population: One participant did not complete the second intervention and was excluded from the data analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buffered Anesthetic | Mean Pain Scores Following Injection | 3.0 score on a scale | Standard Deviation 1.9 |
| Unbuffered Anesthetic | Mean Pain Scores Following Injection | 3.3 score on a scale | Standard Deviation 1.5 |
p-value: 0.38ANOVA
Primary
Mean Time to Baseline Lip Sensation
Response in minutes from injection to when lip is no longer numb, as self reported by patient.
Time frame: Within 24 hours following injection
Population: One participant did not complete the second intervention and was excluded from the data analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buffered Anesthetic | Mean Time to Baseline Lip Sensation | 218 minutes | Standard Deviation 59.6 |
| Unbuffered Anesthetic | Mean Time to Baseline Lip Sensation | 241 minutes | Standard Deviation 91.4 |
p-value: 0.33Sign test
Primary
Mean Time to Lower Lip Numbness Following Injection
Time in minutes beginning immediately following injection to patient-reported lip numbness
Time frame: Up to 30 minutes following injection
Population: One participant did not complete the second intervention and was excluded from the data analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buffered Anesthetic | Mean Time to Lower Lip Numbness Following Injection | 3.4 minutes | Standard Deviation 1.3 |
| Unbuffered Anesthetic | Mean Time to Lower Lip Numbness Following Injection | 4.4 minutes | Standard Deviation 3.7 |
Comparison: Analysis of variance for 2x2 crossover study using the pkcross routine of Stata 16.1 and accounting for sequence and period effects.p-value: 0.28ANOVA
Primary
Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 120 Minutes Following Injection
Response to experiencing sensation to cold stimulus on permanent molar tooth 120 minutes following injection
Time frame: 120 minutes following injection
Population: One participant did not complete the second intervention and was excluded from the data analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Buffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 120 Minutes Following Injection | Negative Response to Cold Testing | 13 Participants |
| Buffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 120 Minutes Following Injection | Positive Response to Cold Testing | 12 Participants |
| Unbuffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 120 Minutes Following Injection | Negative Response to Cold Testing | 19 Participants |
| Unbuffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 120 Minutes Following Injection | Positive Response to Cold Testing | 6 Participants |
Comparison: Test of symmetry (marginal homogeneity, Stuart-Maxwell) implemented using the symmetry routine in Stata 16.1.p-value: 0.26Sruart-Maxwell symmetry test
Primary
Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 30 Minutes Following Injection
Response to experiencing sensation to cold stimulus on permanent molar tooth 30 minutes following injection
Time frame: 30 minutes following injection
Population: One participant did not complete the second intervention and was excluded from the data analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Buffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 30 Minutes Following Injection | Negative Response to Cold Testing | 17 Participants |
| Buffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 30 Minutes Following Injection | Positive Response to Cold Testing | 8 Participants |
| Unbuffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 30 Minutes Following Injection | Negative Response to Cold Testing | 18 Participants |
| Unbuffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 30 Minutes Following Injection | Positive Response to Cold Testing | 7 Participants |
Comparison: Stuart-Maxwell test of marginal homogeneity implemented with the symmetry routine in Stata 16.1p-value: 0.65Sruart-Maxwell symmetry test
Primary
Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 60 Minutes Following Injection
Response to experiencing sensation to cold stimulus on permanent molar tooth 60 minutes following injection
Time frame: 60 minutes following injection
Population: One participant did not complete the second intervention and was excluded from the data analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Buffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 60 Minutes Following Injection | Negative Response to Cold Testing | 17 Participants |
| Buffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 60 Minutes Following Injection | Positive Response to Cold Testing | 8 Participants |
| Unbuffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 60 Minutes Following Injection | Negative Response to Cold Testing | 18 Participants |
| Unbuffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 60 Minutes Following Injection | Positive Response to Cold Testing | 7 Participants |
Comparison: Test of symmetry or marginal homogeneity (Stuart-Maxwell) implemented with the symmetry routine in Stata 16.1.p-value: 0.71Sruart-Maxwell symmetry test
Primary
Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 90 Minutes Following Injection
Response to experiencing sensation to cold stimulus on permanent molar tooth 90 minutes following injection
Time frame: 90 minutes following injection
Population: One participant did not complete the second intervention and was excluded from the data analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Buffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 90 Minutes Following Injection | Negative Response to Cold Testing | 15 Participants |
| Buffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 90 Minutes Following Injection | Positive Response to Cold Testing | 10 Participants |
| Unbuffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 90 Minutes Following Injection | Negative Response to Cold Testing | 18 Participants |
| Unbuffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 90 Minutes Following Injection | Positive Response to Cold Testing | 7 Participants |
Comparison: Test of symmetry (marginal homogeneity, Stuart-Maxwell) implemented using the symmetry routine in Stata 16.1.p-value: 0.32Sruart-Maxwell symmetry test
Primary
Number of Participants Who Respond to Cold Stimulus (Positive/Negative) Prior to Injection
Response to experiencing sensation to cold stimulus on permanent molar tooth prior to injection
Time frame: 5 minutes prior to injection
Population: One participant did not complete the second intervention and was excluded from the data analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Buffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) Prior to Injection | Negative Response to Cold Testing at Baseline | 6 Participants |
| Buffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) Prior to Injection | Positive Response to Cold Testing at Baseline | 19 Participants |
| Unbuffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) Prior to Injection | Negative Response to Cold Testing at Baseline | 2 Participants |
| Unbuffered Anesthetic | Number of Participants Who Respond to Cold Stimulus (Positive/Negative) Prior to Injection | Positive Response to Cold Testing at Baseline | 23 Participants |
p-value: 0.37Chi-squared