Articaine efficacy and safety in young children

below the age of four years: An equivalent

parallel randomized control trial
Ahmad Abdel Hamid Elheeny
Int J Paediatr Dent. 2020;00:1–9.
Presented By: Dr. Shraddha Patil
(1st year PG)
Guided by: Dr. Rashmi Jayanna
Dr. Swapnil Mhatre
Dr. Priyanka Razdan
 INTRODUCTION

• One of the most significant determinants of successful accomplishment of dental

treatment and shaping the child’s later attitude in the dental office is pain control.

• Adequate local anesthesia has an imperative role in pain elimination throughout

the dental setting and subsequent establishment of a positive and effective pediatric
treatment triangle.

• The cardinal aspects of any local anesthetic agent have to be fulfilled are safety and
efficacy.

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• Lidocaine as a member of the amide group was primarily introduced in the middle
of the preceding century.

• As a result of its efficient performance and scarce inimical side effect, lidocaine
gained ubiquitous worldwide popularity and considered as the ‘gold standard’ for
comparison with subsequently introduced local anesthetic agents.

• In 1969, Articaine hydrochloride as new local anesthetic agent emerges.

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• Articaine chemical structure characterized by the existence of a thiophene ring
instead of the ordinary benzene ring that presents in other local anesthetics making
articaine more lipophilic and subsequently increases its potency.

• The other exclusive feature is the presence of ester group.

• These inimitable properties allow the quick hydrolysis of articaine in the blood and
minimize the risk of systemic toxicity.

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•In comparison with lidocaine, articaine is 1.5 times more potent and 0.6 times less
toxic.

• Plenty of literature support the use of articaine pediatric patients for its safety and
efficiency; however, its use is restricted for children above the age of four years
based on the manufacturer's instructions.

• There is no evidence supports that claim and contraindicate the use of articaine
local anesthesia in dental practice for children below the age of four years.

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 AIM
→ To assess the safety and efficacy of 4% articaine local an
esthetic in young children below four years old.

 The null hypothesis of this study (H0) assumed that the

efficiency and safety of articaine and lidocaine were not
equivalent.
On the other hand, the alternative hypothesis (H1)
supports that both local anesthetic drugs are equivalent.
 METHODS

Ethical approval
• All procedures performed in studies involving human participants were under
the ethical standards of the institutional and/or national research committee
(Ethical approval number of 176) and with the 1964 Helsinki declaration and its
later amendments or comparable ethical standards.

• The trial registered at ClinicalTrials.govPRS (Protocol registration and Result

System) under a number of NCT04061265.

• Informed consent was signed by the participants’ parents/legal guardians

before launching the procedures
 Setting, design, and sample size calculation

• This trial carried in the outpatient clinic, Pediatric Dentistry Department,

Faculty of Dentistry, Minia University.

• The trial was held between August 2019 and completed in January 2020.

• The study was equivalent randomized control trial with two parallel arms.

• The sample size per group was calculated according to the following equation
for binary outcomes; N = 2*(Zα/2 + Zβ)2*p(1 − p)/δ2.8
 Setting, design, and sample size calculation

• The level of significance 5% (P ˂ .05), power of the trial= 80% (β = 0.2).

• An additional 10% of participants were added to compensate for the

withdrawal bias.

• Therefore, 92 children per group (total of 184 children) were suitable to declare
the difference if present between the two local anesthetic agents at 95%
confidence level (95% CI).
 Randomization, allocation, and blinding

• Out of examined 239 children, 184 children who met the inclusion criteria were
selected.

• An independent clinician was responsible for generating a random allocation

sequence that kept hidden from all the trial participants.

• Based on local anesthetic drugs, the participants were assigned equally into two
groups using a computer-generated block randomization technique.

• Randomization was performed using online databases for clinical trials at

https:// www.seale denve lope.com/simple-rando miser/ v1/lists.
 Randomization, allocation, and blinding

• The printed letters were folded several times and placed within an aluminum foil.

• An additional task performed with the independent nurse was the peeling of the
manufacture's local anesthetic cartridge and relabeled with an identification code.

• The letter and relabeled local anesthetic cartridge placed inside an opaque sealed
and stapled envelope, including patient's identification code, name, time, and date.

• The nature of treatment was masked for the patient/parents, chief investigator who
performed the clinical procedures and the two dental clinicians who assess the
child's behavior and pain intensity.
 ELIGIBILITY CRITERIA

Inclusion  Class I and Class II ASA classification

standards  Child's age was between 36 and 47 months inclusive
 Intellectually qualified for communication
 Child's body weight must be at least 15 kg
 Mandibular primary molars indicated for pulpotomy (ie,
carious teeth with vital pulp exposure, normal clinical, and
radiographic findings with no evidence of pulp degeneration)

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 ×
Exclusion  History or signs of swelling, inflammation, mobility, fistulous
tract, or periapical lesion, which confirmed with pre-
standards operative periapical radiograph at or close to the injection
site
 Intellectual or severe emotional problems
 Considerable behavior problems
 Parents refuse participation in the trial
 History of previous dental experience
 Past dental visit to not influence child perception

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 Standardization and calibration

• Before launching the investigation, all dental staff (clinicians and assistants) took part
in the investigation trained for one day on the clinical steps and assessment scale.

• The local anesthetic injection and pulpotomy conducted by one investigator.

• Two pediatric dentists with at least 5 years of experience evaluated and recorded the
scores of a pain assessment tool using Faces, Legs, Activity, Cry, and Consolability
(FLACC) and child's behavior using Frankl Behavior Rating Scale (FBRS).

• The inter-observer reliability (Cohen's kappa coefficient χ) was calculated.

Clinical procedures and post-operative negative reaction
evaluation
• The dose of each local anesthetic drug adjusted based on each child's weight taking
part in the investigation.

• Topical anesthesia did not apply to allow accurate calculation of the drug dose and
obviate drug toxicity.

• Alternatively, non-pharmacological behavior management such as a distraction

technique was considered.

• Aspirating syringe with a 30-gauge short needle (Sirio, Tecnofar, Italy 0.30 × 12 mm)
was used for buccal infiltration injection.
• The anesthetic solution injected near the distal root apex of the intended
mandibular primary molar at a rate of 1 mL/min.

• Local anesthetic drugs were lidocaine hydrochloride 2% and epinephrine 1:100 000
(Lignospan® standard, 1.7 mL, SEPTODONT Ltd) for the control group. ‘

• The intervention group received articaine hydrochloride 4% and epinephrine 1:100

000 (Septocaine® 1.7 mL, SEPTODONT Ltd).

• The maximum recommended dose for lidocaine and articaine calculated according
to the AAPD guidelines was 4.4 and 5 mg/kg, respectively.
• The maximum dose, however, adopted for articaine was 5 mg/kg.

• The treatment deemed to be unsuccessful in case of failure to complete the

pulpotomy procedures and reschedule.

• Vital signs including blood pressure, heart rate, and respiratory rate were measured
at 3 occasions; the first before injection, the second was 5 minutes following the
injection, and the third occasion was immediately after finishing the pulpotomy.

• After 24 hours, the chief investigator inquired from the parent about the child's post-
operative pain using as parents' post-operative pain measure (PPPM) and any
undesired adverse effects.
 Definition of different study outcomes

• The different scales used in this trial defined based on binary outcomes as follows:

• Faces, Legs, Activity, Cry, and Consolability (FLACC) dichotomized into

 no or mild pain (0-3)
 moderate to severe pain (4-10)

• Frankl Behavior Rating Scale (FBRS) dichotomized into

 positive (behavior rating 3 or 4)
 negative (behavior rating 1 or 2)
 Definition of different study outcomes

• Local anesthesia delivery success dichotomized into

 no (0) and yes (1)

• Parents' post-operative pain measure (PPPM) dichotomized into

 absent (0-5) present (6-15)

• Post-operative lip pr cheek biting, use of medication and/or others dichotomized

 into no (0) yes (1)
 Statistical analysis
• The descriptive baseline characteristics of the participants in the experimental and control
groups were analyzed using frequency tables, mean and standard deviation (SD), chi-square
test, and t test.

• To test the equivalence between the two local anesthetic agents, on the basis of success
rates of articaine and lidocaine from previous literature, the margin of equivalence (±δ) was
adjusted at 20%.

• The absolute risk difference (ARR) of success rates of the two anesthetic drugs was
calculated at 95% confidence interval (95% CI) and 5% cutoff point of the level of
significance (P ˂ .05).

• Equivalence was announced when the ARR exited within the margins of equivalence (±δ =
0.2).
 RESULTS

Baseline
characteristics of
children, tooth type,
and dental
procedures
 RESULTS

Vital signs of
children
in lidocaine and
articaine groups at
three
different occasions
Success and failure
rates of
lidocaine and
articaine at
administration and
during pulpotomy
 Frankl's Behavior Rating Scale

• The success rate of articaine during injection and throughout pulpotomy was 81.5%
and 87%, respectively.

• Although the success rate in the lidocaine group was 79.3% at local anesthetic
administration and 78.3% during the treatment, absolute risk difference between
articaine and lidocaine groups during local anesthetic administration and treatment
procedures was 0.022 (95% CI −0.093; 0.136) and 0.087 (−0.023; 0.196), respectively.

• Both 95% CI limits were within the margin of equivalence boundaries (±δ = 0.2)
suggesting that the two anesthetic drugs were equivalent.
Post-operative side
effects
of lidocaine and
articaine
 DISCUSSION

• Most dental procedures relay on local anesthesia for pain control.

• However, Local anesthetic injection, represents the major source of anxiety

stimulation especially in pediatric patients.

• Despite the wide use of articaine in pediatric dentistry because of its proved
effectiveness and safety, articaine application in children below the age of four years
is still argumentative.

• Concerning the use of articaine in very young children, the available data are still
very deficient.
• Therefore, the current prospective equivalent trial has been conducted to examine
the safety and effectiveness of articaine in pulpotomy procedures in children aged 3-
to 4-year-old.

• The scientific background of this study based on the results of a retrospective study
records conducted on 211 pediatric children under the age of four from two
pediatric dental offices in Canada.

• Children have been assigned into two groups, the first group treated under sedation
with the use of articaine local anesthesia and in the second group children have
received articaine local anesthesia solely.

• The findings in both groups revealed no systemic adverse reactions.

• Another article has been conducted to test the effectiveness of infiltration
anesthesia using 4% articaine in comparison with mepivacaine hydrochloride 2%,
prilocaine hydrochloride for cavity preparation and rubber dam application among
66 young children aged between 42- and 72- month-old.

• For standardizations, only one painful procedure (ie, pulpotomy of the mandibular
primary molars) using infiltration anesthesia has been adopted to perform this study.

• Although development of children's cognitive ability for discrimination between

different pain intensity scales.
• For that reason, the present trial depended on an objective measure to assess pain
at injection and during treatment.

• FLACC pain scale has been nominated to fulfill such task for several rationales
including the following:
 suitable objective tool for the age group from two months up to seven-year-old,
 improved to have excellent reliability and validity
 has appropriate psychometric properties.

• To evaluate the anxiety in dental sitting, FBRS has been applied in the present trial
because of its simplicity, higher reliability, and its immense use of literature.
• A direct comparison between the findings of previously published literature was an
intractable issue for a group of considerations.

 The limited number of investigations concerned with age below of four years
 the diversity in study design, sample size, and inclusion specifications
 the use of variable tools for pain assessment.

• Concerning articaine efficacy, most published articles among pediatric patients

pointed out that articaine infiltration showed comparable or higher results over
lidocaine, which was in line with the findings of this study.
• For instance, a former trial has reported a 71% successful buccal infiltration
anesthesia of articaine versus 64% for lignocaine among 56 children with an average
age of 12.9 years.

• Another prospective random trial was conducted on 62 children aged from 5 to 13

years old recorded that no difference in pain using Wong-Baker FACES pain rating
scale between 2% lidocaine with 1:100 000 epinephrine and articaine 4% with 1:200
000 epinephrine.

• Furthermore, an equivalent randomized controlled trial reported that the success

rate of 4% articaine mandibular buccal infiltration was 73.5% using Visual Analogue
Scale (VAS) and 79.6% for lidocaine group using the same subjective assessment
tool.
• Articaine and lidocaine were equivalent during anesthetic injection. While during
treatment, the two anesthetic drugs were not equivalent with little number of cases
expressed pain in the articaine group in comparison with those received lidocaine
anesthetic agent.

• These findings were opposite to Alzahrani et al, who reported non-equivalence while
the anesthetic drug was administrated via buccal infiltration and inferior alveolar
nerve block.

• On the other hand, equivalence has been detected during treatment procedures.

• Pain severity associated with inferior alveolar nerve block was higher compared to
infiltration injection.
• Another article concluded that the efficacy of lidocaine and articaine was similar
during buccal infiltration and inferior alveolar nerve block of 62 children with an age
group ranged from 5 to 13 years.

• With respect to vital signs, this study displayed that there was no statistically
significant difference between articaine and lidocaine.

• These findings were in line with the finding of Odabaş,et al who concluded that
blood pressure, heart rate, or oxygen saturation were within the normal range
immediately after maxillary injection and post-intervention with articaine 4% with
1:200,000 epinephrine.
• In addition, Mitta et al reported no statistically significant difference in the
hemodynamic records when compared the efficacy of lidocaine to articaine during
extraction of maxillary primary molars, and these observations were suitable with
the findings of this study.

• Regarding the post-operative negative reactions, no significant differences between

the articaine and lidocaine groups have been identified.

• Post-operative pain and analgesics were likely attributed to the self-injurious

lip/buccal mucosa or the pulpotomy procedure itself and not be connected to the
type of local anesthetic agent.
• Regarding the post-operative negative reactions, no significant differences between
the articaine and lidocaine groups have been identified.

• Post-operative pain and analgesics were likely attributed to the self-injurious

lip/buccal mucosa or the pulpotomy procedure itself and not be connected to the
type of local anesthetic agent.

• Previous literature studied the post-operative reactions after articaine injection for
50 children between 4 and 13 years old, only one case suffered from accidental lip-
biting which less than recorded in this study.

• This might be due to the younger age of children recruited in this study
 MERIT

 adequate number of participants, which ensured

sample representativeness
 the dependence on objective tools with high
reliability and validity for pain assessment
 the inter-observer reliability was high, and finally
 The rigorous actions have been taken to avoid any
bias such as double-blinding and assessment
unprejudiced candidates.

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DEMERITS

 20% difference was established on the

basis of previous literature of how the
2 anesthetics compare, rather than
considerations of what would be
acceptable to clinicians
 ●lack of assessment of the pharmacokinetics of the
articaine.

●Short follow-up period (24 hours).

24 hours, however, was an enough time to address
LIMITATIONS
delayed complications after the treatment session,
to determine whether any adverse reaction
occurred and also, the onset of classic presentation
of local anesthetic systemic toxicity (prodromes,
central nervous system, and cardiovascular system
syndromes) is <5 minutes
 Why this paper is important to pediatric
dentists?
 Buccal infiltration with Lidocaine in a painful procedure such as pulpotomy
may not be sufficient. Therefore, the introduction of another safe and more
potent anesthetic drug will be more beneficial.

 Despite the manufacturer's instructions do not recommend the use of

articaine in children below the age of four years old, there is no evidence
support this claim.

 The current trial revealed the efficiency of articaine administration with

comparable results to lidocaine.
 CONCLUSION

 This study supported the secure use of articaine

hydrochloride 4% with epinephrine 1:100 000 for
treatment of children between the age of 3 and below
4 years old.

 Its safety was comparable to lidocaine hydrochloride

2% and epinephrine 1:100 000.

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Efficacy of articaine: a new amide local anesthetic
S F Malamed , S Gagnon, D Leblanc
JADA, 2000, May, 135(5) 165

● The authors compared the safety and efficacy of 4 percent articaine with
epinephrine 1:100,000 with 2 percent lidocaine with epinephrine
1:100,000.

● In three identical randomized, double-blind, multicenter trials, subjects 4 to

80 years of age received either 4 percent articaine with epinephrine
1:100,000 or 2 percent lidocaine with epinephrine 1:100,000 for simple or
complex dental procedures.

● Efficacy was determined by both subject and investigator using a visual

analog scale, or VAS.
 Conclusion
● The authors found that 4 percent articaine with epinephrine 1:100,000
was well-tolerated in 882 subjects.

● It also provided clinically effective pain relief during most dental

procedures and had a time to onset and duration of anesthesia
appropriate for clinical use and comparable to those observed for
other commercially available local anesthetics
The Use of Articaine Local Anesthesia In Children Under 4 Years of Age—A
Retrospective Report
Gerald Z. Wright,Sergio J. Weinberger,Clive S. Friedman, Olaf B. Plotzke
Anesth Prog 36:268-271 1989

● Articaine anesthetic was administered to 211 patients, 29 having additional

administrations of the agent.

Conclusion :
● No adverse systemic adverse reactions were noted on the charts or known
to the clinicians.
● The present retrospective study supports the use of articaine in children
under 4 years of age.
Thank You!

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