Comparative Study of the Anaesthetic Efficacy of 4% Articaine Versus 2% Mepivacaine in Mandibular Third Molar Germectomy Using Different Anaesthetic Techniques: a Split-mouth Clinical Trial
Phase: NA
Conditions: Local Anesthetic Efficacy
Sponsor: University of Campania Luigi Vanvitelli

 
 
Comparative study of the anaesthetic efficacy of 4% 
articaine versus 2% mepivacaine in mandibular third 
molar 
germectomy 
using 
different 
anaesthetic 
techniques: a split-mouth clinical trial. 
 
 
*Menditti D., *De Rosa A., *Nucci L., **Ribeiro Sobrinho A.P. *Laino L., *Guglielmotti M., 
*d’Apuzzo F., *Menditti M., ***Boccellino M., ****Rinaldi B. 
 
*  
Multidisciplinary Department of Medical-Surgical and Dental Specialties, University of Campania Luigi Vanvitelli, Naples, Italy. 
**  
Department of Operative Dentistry, School of Dentistry, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. 
***  
Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy. 
****  
Department of Experimental Medicine, University of Campania Luigi Vanvitelli, Naples, Italy. 
 
 
 
 
 
 
April 20, 2020 
 
 

ABSTRACT 
Aim: To compare the clinical efficacy of local anaesthetics with articaine 4% or mepivacaine 2% 
(both with epinephrine 1:100.000) using different anaesthetic techniques to perform germectomy 
of lower third molars and to assess patients' feelings and pain during surgery. 
Methods: 50 patients (ranged 11-16 years) who required germectomy of mandibular third molars 
were recruited. Each patient received local anaesthesia on one side with articaine inoculated with 
plexus technique while on the other side with mepivacaine using inferior alveolar nerve block 
technique. The patients' evaluation was performed on pre and intraoperative tactile-pressure 
feelings and intraoperative pain with four levels on the analogic visual scale (VAS). 
Results: Surgical operations lasted less with more efficient analgesia when articaine was used. 
The additional intraosseous injection was required mainly in the mepivacaine group 
intraoperatively. A few patients had tactile-pressure feelings while intraoperative pain sensation 
was absent in 90% of cases with articaine. Significant differences were found in the cases who 
reported "absent" and "moderate" VAS values, favoring the use of articaine. 
Conclusion: Articaine injected with a plexus anaesthetic technique seems to be more clinically 
manageable than mepivacaine for the mandibular third molar germectomy. The discomfort of 
tactile-pressure feelings and pain experienced was lower using articaine anaesthetic technique 
used. 
 
KEYWORDS 
Local Anaesthetic, Articaine, Mepivacaine, Third Mandibular Molar, Germectomy 
 
INTRODUCTION 
The surgical extraction of a tooth that exhibits at least a third of its root in formation, with a 
periodontal ligament discernible on panoramic x-ray, is defined as germectomy. Early germectomy 
is a useful intervention to avoid several problematics caused by lower third molar retention and 

impaction, and it is often required before or after orthodontic treatment [1-4]. This surgical 
technique would also allow to avoid complications, such as inferior alveolar and lingual nerve 
damage [3-6]. 
The control of the patient's pain and anxiety by using efficient anxiolytics and local anaesthesia is 
essential in oral surgery [7]. These aspects become important in adolescents, above all in the case 
of third molar germectomy [8]. Local anaesthetic (LA) injection is often the only painful part of 
the dental procedure, and the fear associated with this technique is the main reason that leads 
patients to avoid dental treatment [9]. A study by Kaufman [10] assessed and compared the pain, 
pressure and discomfort induced by four intraoral LA injection techniques. The results indicated 
that the inferior alveolar nerve block (IANB) is the most painful while the local infiltration is the 
least painful probably because the submucosa area has fewer number of free nerve endings 
compared to the oral mucosa and the periodontium. Among the possible ways to minimize the 
discomfort perceived at the time of injection, the distensibility of the tissues through short tremors 
(trembling) of the mucous membrane to be stung can be used [11].   
During the execution of these surgical procedures, anaesthesia of the structures innervated by the 
mandibular nerve is necessary, and many local anaesthetic techniques are described in the literature 
[12]. Generally, infiltration plexus technique is usually performed for maxillary procedures while 
IANB is used for molar mandibular sites with 2% local anaesthetics [4-8]. Failure rates for IANB 
are high, sometimes reaching 80% for the lower incisors with this technique, and numerous 
approaches for the implementation of a new technique of IANB have been described [13].  Among 
them, the articaine 4% already has been successfully used to achieve local anesthesia [14-17] and 
facial infiltration anaesthetic technique in the mandible showed efficacy with encouraging result 
that can be overlapped to the IANB technique [13]. Articaine (4-methyl-3-[2-(propylamino)-
propionamido]-2-thiophene-carboxylic acid, methyl ester hydrochloride) contains a thiophene ring 
instead of benzene and an ester group. The thiophene ring allows for higher lipid solubility so a 
greater portion of an administered dose can enter in neurons. Gazal et al. [17] found that a 

combination of nerve block anaesthesia, buccal infiltration and intra-ligamentary injection resulted 
in more profound anaesthesia (P =0.003) and higher success rates compared to IANB alone in 
mandibular first molar pulp anaesthesia. Other studies reported the use of articaine in implantology 
interventions in which it was used with subperiosteal technique on the buccal and vestibular sides 
[18]. 
Thus, the literature showed several conflicting results on the mandibular facial plexus infiltration 
technique used with different anesthetics [6,8,14]. 
Recent studies of this anaesthetic technique found that 1.8 cc of 4% articaine facial infiltration in 
the mandible can be effective when the thickness of mandibular facial cortex is < 2.0-3.0 mm, with 
5-10 minutes needed for the adequate anaesthesia, and often an additional 1.8 cc of the dose was 
required to obtain anaesthesia in adult patients [13-15]. 
It was reported that many dental procedures on deciduous molars could be accomplished with 
infiltration of articaine alone in the pediatric population [19]. 
As above mentioned, the difficulty in achieving reliable anaesthesia in the third mandibular molars 
in adults with facial infiltration of local anaesthetic is related to the thickness of the cortical bone 
and inability to achieve consistently inferior alveolar nerve [12]. An ideal local anaesthetic should 
have the following characteristics: a) short latency time; b) strength of the intense effect; c) 
duration of prolonged action; d) lack of harmful local and systemic effects [19-20]. 
Currently, mepivacaine is among the most used and studied anaesthetics in dentistry [17]; however, 
articaine is nowadays increasingly used for its manageability, lack of side effects and high 
anaesthetic potency [13,21,22]. Mepivacaine is an amide-type anaesthetic with fast action from 
the beginning and 30-120 minutes duration. Its maximum allowed dose is 300 mg with epinephrine 
or 500 mg alone. The dose for children is 4-6 mg/kg/dose (maximum: 270 mg) without epinephrine 
[19].         
 Articaine, due to its chemical characteristics, is quickly soluble and rapidly released from 
adipose/lipid tissue. The ester side chain of articaine is hydrolyzed by plasmaesterases rendering 

the molecule inactive. Evidence suggests that it is the local anaesthetic that best spreads within 
soft and hard tissues 23. Then, it has a non-conducive effect on extended operations having a 
shorter half-life of 25 minutes compared to approximately 90 minutes of other amides (115 minutes 
for mepivacaine) that require hepatic clearance [24]. Accordingly, it was suggested that articaine 
does not own any relevant side effects or systemic toxicities [25]. 
For this reason, articaine has been used at higher concentrations (4%), associated with epinephrine, 
compared to other local dental anesthetics [26].  This higher concentration ensures an excellent 
spread both in hard and soft tissues, also promoted by a pKa (7,8) very similar to the physiological 
pH of tissues. Its great liposolubility allows a rapid diffusion in adipose tissue (spread coefficient 
= 17,0) and involves a lower adherence to the nerve membranes and, above all, lower toxicity for 
the tissues. Moreover, articaine has a high protein-based bond (94%) which allows a better affinity 
for the protein-based membrane receptors, and it is a direct sign of its increased anaesthetic potency 
[19,27-29]. 
Dental local anaesthetics are often combined with vasoconstrictors, such as epinephrine, to 
increase the depth and duration of analgesia [24,29]. Clinical experiments, in which articaine 
without vasoconstrictor was used, did not show any satisfying results [30], whereas the use of 
articaine combined with low concentrations of vasoconstrictors produced better anaesthetic effects 
than other common local anaesthetics such as bupivacaine [31] and mepivacaine [32]. It is well 
documented that vasoconstrictors have a safety range [33] if used at low doses, and not directly 
injected in the blood vessels, even in particular care patients [34,35]. 
The present study aimed to compare the clinical efficacy of articaine 4% (epinephrine 1:100.000) 
versus mepivacaine 2% (epinephrine 1:100.000) for the surgical germectomy of mandibular third 
molars with two different conventional anaesthetic techniques in young patients whom jawbone is 
not completely mineralized yet and more penetrable by the articaine molecule. 
 
MATERIALS AND METHODS 

This observational prospective split-mouth clinical trial was performed at the Oral Surgery of the 
University of Campania “Luigi Vanvitelli”. Fifty patients, aged between 11 and 16 years old, 
requiring bilateral germectomy of mandibular third molars before orthodontic treatment, after 
evaluating their panoramic x-ray, were consecutively recruited between June 2018 and October 
2019 (Table 1). The subjects were children undergoing orthodontic treatment in whom early 
extraction was indicated to facilitate their treatment in some specific conditions (i.e. posterior 
crowding, altered second molar eruption, non-extraction approach) [1,2]. Thus, patients were 
checked for the fulfilment of inclusion criteria through medical history collection and clinical 
examinations, then routine blood tests were made before intervention. All included patient’s 
parents gave informed written consent after providing them with detailed information and the 
guidelines approved by the Ethics Committee of the University of Campania “Luigi Vanvitelli” 
(Prot. number 6251) were followed in this investigation. At the preliminary visit, a good 
explication on the surgical procedures was provide to encourage the compliance of young patients 
and their parents. 
Exclusion criteria were patients presenting systemic and oral diseases, overweight, and allergy to 
the drugs and substances used during the surgical intervention. If the anaesthesia was not adequate 
with one of the two techniques, or if the patient, already included in the study, presented an 
excessive anxiety state, the patient was also excluded from the analysis. 
Germectomy, defined as the removal of an impacted tooth with at least a third of its root 
information with a periodontal ligament discernible on panoramic x-ray, was the surgical operation 
planned in the present study. 
The type of local anaesthesia (solution containing mepivacaine 2% with 1:100.000 epinephrine or 
solution containing articaine 4% with 1:100.000 epinephrine) and the related technique to be used 
on the right or left side were randomly selected using a computerized randomization program 
before starting the protocol. In Table 2 are shown the pharmacokinetic parameters of the two 
anaesthetics. 

For each subject, the first germectomy was scheduled 15 days apart. The same senior operator, 
assisted by the same practitioner, completed all the surgical procedures. All interventions made 
with mepivacaine were performed with the same anaesthetic technique routinely used in Oral 
surgery (IANB). The technique was complemented with anaesthesia of the buccal nerve, as routine 
for this technique, administering another 1.8 ml of the same anaesthetic used in each intervention. 
On the other hand, the surgical procedures in articaine cases were made practising a plexus 
technique, performing a deep buccal injection distally to the second mandibular molar. 
At the first intervention, patients received mepivacaine 2% with 1:100.000 epinephrine or articaine 
4% with 1:100.000 epinephrine. In the articaine group, an alternative procedure was applied to 
perform a plexus technique on the buccal side distal to the second mandibular molar region. Two 
injections of articaine were performed. Firstly, equivalent to one-quarter of the cartridge was 
injected in the buccal fornix in the sovraperiosteal area of the lower third molar. It was asked to 
practice a trembling manoeuvre to prevent patients from perceiving the discomfort of the first 
puncture, avoiding the pain by the next injection in the deeper tissues. Secondly, it was used the 
rest of the cartridge, approximately after three minutes deeper in the subperiosteal area at the same 
point with direct contact to the mandibular cortical bone. It was not necessary to provide an 
additional injection of anaesthetic to obtain lingually anaesthesia in the articaine groups. During 
the surgical procedures, an additional injection of anaesthesia was requested mainly in the 
mepivacaine group. 
Once performed the injections, patients were asked to notice on a visual analogue scale (VAS) [7],  
how much discomfort they felt due to the anaesthetic injections. Moreover, patients were asked to 
notice, after 6-8 minutes from the injection, the tactile and pressure feelings on the same VAS 
scale. These perceptions were stimulated using a periodontal probe applied distal to gingiva of the 
second mandibular molar on the same side of the intervention. The same pressure and tactile tests 
were repeated intraoperatively directly on the exposed bone using the same method. Finally, a 
mucoperiosteal flap was lifted, without vertical releasing incisions were not required, followed by 

germectomy of the third mandibular molar. 
At the end of each surgical operation, patients were asked to notice intra-operative pain on another 
visual analogue scale (VAS) with four different levels of pain: absent (0), mild (1), moderate (2), 
high (3) [7]. All interventions were performed with the same surgical technique and completed 
with satisfactory results without any intra-operative and post-operative complications. All patients 
were discharged after nearly 2 hours from the end of the intervention giving home instructions, 
and antibiotic and anti-inflammatory medical coverage. The suture applied at the end of surgery 
was removed seven days after surgery. Student t-test statistical analyses were performed to 
compare the VAS results. 
 
RESULTS 
In the mepivacaine group, the mean time between injection and full anaesthetic effect ranged 
between about 7 minutes. In 40 patients (82%) additional intraosseous injection (Table 3) (0.5 ml, 
45% of one cartridge) was requested intraoperatively on the bone, limited to the duration of the 
intervention on the bone. The average time of surgical procedures was 25 minutes, with a minimum 
of 20 minutes and a maximum of 30 minutes. 
In the articaine group, it took about 4 minutes to achieve full anaesthesia after the second 
inoculation. In 21 cases (mild/moderate pain), additional intraosseous injections were needed 
(42%): it was practiced because patients asked for maximum comfort (0.2 ml). The average time 
of the operations was approximately 20 minutes, with a minimum of 15 and a maximum of 25 
(Table 3). 
After 6-8 minutes from IANB anaesthesia/buccal nerve block and plexus technique, tactile-
pressure feelings were recorded, as in a previous study [25]: in the mepivacaine group no patients 
experienced severe tactile-pressure feelings, but 40% had them in other categories, whereas in the 
articaine group, 70% of patients did not experience any tactile-pressure feelings (Tables 4, 5). 
About the intraoperative tactile-pressure feelings, in the mepivacaine group in 60% of cases a 

moderate/severe solicitation was experienced, mild in 16% of cases and absent only in 24% of 
interventions; in the articaine group, tactile-pressure feelings were absent in almost all 
interventions (43 cases) (Tables 4, 5). 
According to VAS during intraoperative pain sensation, the results were more homogeneous in the 
articaine group than in the mepivacaine one: in the articaine group, it was absent in 90% of cases 
(Tables 4, 5). 
One of the most exciting aspects was that the youngest patients of our sample (11-13 years old, 
50%) reported the best comfortable feelings, either post-operative. 
The results of patients' feelings and pain after the use of the two different anaesthetics present 
statistically significant differences (P <0.05) in the cases that were reported "absent" and 
"moderate" VAS values, favoring the use of articaine (Table 6). 
Additionally, patients who received supplementary articaine injections verbally reported that the 
sufficient anaesthetic period was prolonged for approximately 2-3 hours. All patients experienced 
a high degree of discomfort with intraoral IANB due to the anaesthetic injection puncture 
performed through the internal pterygoid muscle. Conversely, as expected, the buccal plexus 
anaesthesia realized with the technique of the two subsequent injections of progressive depth did 
not leave in the patients any memory of discomfort injection. 
 
DISCUSSION 
Our preliminary results showed how it could be possible to avoid the painful and unpleasant 
sensation due to the traditional IANB technique injection through the internal pterygoid muscle 
taking advantage of the plexus technique allowed by the use of articaine. Moreover, this plexus 
technique avoids the need for a double injection that is performed typically in IANB technique, 
when a supplementary puncture is requested to block the buccal nerve and often on the lingual 
side. Lastly, no additional injection of anaesthetic was needed to obtain lingual anaesthesia in the 
articaine cases. 

In our opinion, these data are clinically crucial for all patients, particularly for the younger and for 
all those patients that never experienced any dental treatment before, often generating the well-
known "odontophobia". These shreds of evidence could lead to reducing the number of patients 
requiring dental care under general anaesthesia with less risk of damage to their health, the chance 
of unpleasant anaesthetic complications, respecting the cost-containment social. In addition, 
trismus and nonsurgical paresthesia, as results of damage caused by the needle to the inferior 
alveolar and lingual nerves, could be avoided. 
The faster activation of drugs could explain the difference in latency time between articaine and 
mepivacaine that we experienced in our study with lower pKa and by the strong aptitude of 
articaine in bonding proteins, especially those of nervous tissue [19]. 
Moreover, these peculiarities promote deep anaesthesia that makes more comfortable performing 
the surgical germectomy of third mandibular molars, favoring more tranquility and collaboration 
from young patients: this can be related to shorter interventions (15-25 minutes) compared to 
mepivacaine (20-30 minutes). On the other hand, patients who received supplementary articaine 
intraosseous injections reported that the sufficient anaesthetic period was prolonged for 
approximately 3-4 hours, agreeing with results retrieved in literature [35,36]. Moreover, in our 
study it was never necessary to practice the IANB in the articaine group before starting the surgical 
procedures. 
These data, combined with the lack of need for additional anaesthesia, represent an unquestionable 
benefit for using articaine as this reduced the waiting time between one patient and another and 
the psychological stress for patients undergoing surgical interventions, also avoiding the lower lip 
anesthesia [25]. 
Our choice of articaine instead of mepivacaine is widely supported in the literature, whereas the 
choice of a buccal plexus injection is justified by other experiences that confirmed the anaesthetic 
effect in case of pulpitis [37,38]. Borchard [39] believes that a local anaesthetic at the concentration 
of 4% is more long-lasting and has a higher effect than a concentration of 2%, denying the 

hypothesis of a higher toxicity. Dudkiewicz [40] reported that, in the mandible, articaine HCl owns 
a partition coefficient higher than lidocaine (123.0 versus 10.0) that provides the physiochemical 
evidence to support the contention of better penetration and diffusion of articaine HCl. Significant 
differences were detected in time of onset and duration of action. The onset described in literature 
[41] as well as the anaesthetic duration of 4% articaine with 1:100.000 epinephrine is per our 
results. Articaine affinity for the membrane receptors of nerve cells is confirmed by anatomical 
studies on the trigeminal nerve and its selective block, which reported how the anaesthetic 
diffusion is related to the different diameters of different nervous fibres [42]. First fibres to be 
blocked are C-ones with the related lifting of the thermal sensitivity and burning pain, then A-  
fibres with loss of the cold+ sensitivity and stinging pain. At last, also A-  fibres, that have the 
largest diameter, are blocked, losing tactile-pressure feelings [21,23,29]. 
Hence, after combining our results with the literature data on the physiology of the trigeminal 
nerve, it is possible to state the efficacy and depth of articaine in its selective and complete block 
action of nervous fibres, which resulted in being higher than with mepivacaine [43]. 
Authors of a recent systematic review with meta-analysis investigated and compared the efficacy 
and safety of articaine with lidocaine [44]. They found out that 4% articaine with 1:100.000 
epinephrine showed a higher success rate in anaesthesia, lower VAS scores during injection phase 
and treatment phase, shorter onset time of pulpal anaesthesia and a lower percentage of patients 
experiencing adverse events. This study also confirmed other advantages with the use of articaine 
described in literature, such as less painful injection, faster onset of effect, with fewer adverse 
events, also avoiding pre-sedations used to reduce the intensity of anxiety in young patients during 
third lower molar extractions [45]. 
 
CONCLUSIONS 
This study showed the differences in terms of tactile pressure and pain feelings, between the two 
anaesthetic drugs used with different anesthesiological techniques, which were assessed with VAS 

encouraging the choice of articaine versus mepivacaine in the third molar germectomy in young 
patients. It should also be noted that the most effective anaesthetic effect was obtained by using 
articaine with a more comfortable and less painful anaesthetic technique, thanks to its intrinsic 
chemical characteristics, that reduce the unpleasant feelings due to classic IANB that involves a 
crossing of muscle fibres of the internal pterygoid muscle. 
In conclusion, articaine has been found to provide significant clinical efficacy compared to 
mepivacaine. Moreover, it was observed shorter latency times, better anaesthetic quality, both pre 
and intraoperatively. Articaine requires less additional anaesthetic than mepivacaine and presents 
better patient compliance with a less unpleasant memory of the intervention. Further studies are 
necessary to determine clinical efficacy using articaine without IANB. 
 
 
AUTHOR CONTRIBUTIONS 
Conceptualization, D.M., B.R.; Methodology, L.L., F.D.; Validation, M.B., D.M.; Investigation, 
L.N., M.G., M.M.; Data Curation, L.N., M.G.; Writing – Original Draft Preparation, M.B., M.M.; 
Writing – Review & Editing, F.D., A.P.R.S.; Supervision, A.D.R.; B.R.; Funding Acquisition, 
A.D.R. 
All Authors have approved the submitted version and agree to be personally accountable for the 
author’s own contributions and for ensuring that questions related to the accuracy or integrity of 
any part of the work are appropriately investigated, resolved, and documented in the literature. 
 
 
 
CONFLICTS OF INTEREST  
The authors declare no conflict of interest. 
 
 
REFERENCES 
1. 
Perillo L, Vitale M, d’Apuzzo F, Isola G, Nucera R, Matarese G. Interdisciplinary approach 

for a patient with unilateral cleft lip and palate.Am J Orthod Dentofacial Orthop. 
2018;153(6);883-94. PMID: 29853246 
2. 
Raucci G, Pachêco-Pereira C, Elyasi M, d'Apuzzo F, Flores-Mir C. Perillo L. Short- and 
long-term evaluation of mandibular dental arch dimensional changes in patients treated 
with a Lip Bumper during mixed dentition followed by fixed appliances. Angle Orthod. 
2016;86(5):753-60. PMID: 26771718 
3. 
Chiapasco M, Crescentini M, Romanoni G. The extraction of the lower third molars: 
germectomy or late avulsion?. Minerva Stomatol 1994;43(5):191-8. PMID: 8072466 
4. 
Rayati F, Noruziha A, Jabbarian R. Efficacy of buccal infiltration anaesthesia with 
articaine for extraction of mandibular molars: a clinical trial. Br J Oral Maxillofac Surg. 
2018;56(7):607-10. PMID: 29980352 
5. 
Almpani K, Kolokitha O. Role of third molars in orthodontics. World J Clin Cases. 2015; 
3(2):132-40. PMID: 25685759 
6. 
Bjørnland T, Haanaes HR, Lind PO, Zachrisson B. Removal of third molar germs. Study 
of complications. Int J Oral Maxillofac Surg. 1987;16(4):385-90. PMID: 3117908 
7. 
Eccleston C. Role of psychology in pain management. Br J Anaesth. 2001;87:144-52.  
PMID: 11460803            
8. 
Gunter JB. Benefit and risks of local anesthetics in infants and children. Paediatr Drugs. 
2002;4(10):649-72. PMID: 12269841 
9. 
Milgrom P. Four dimensions of fear of dental injections. J Am Dent Assoc. 1997;128:756-
62. PMID: 9188235 
10. 
Kaufman E, Epstein JB, Naveh E, Gorsky M, Gross A, Cohen G. A survey of pain, 
pressure, and discomfort induced by commonly used oral local anesthesia injections. 
Anesth Prog. 2005;52(4):122-7. PMID: 16596910 
11. 
Malamed SF. Handbook of Local Anesthesia. 4th ed. St Louis, Mo: CV Mosby; 1997. 
12. 
Khoury J, Townsend G. Neural blockade anaesthesia of the mandibular nerve and its 

terminal branches: rationale for different anaesthetic techniques including their advantages 
and disadvantages. Anesthesiol Res Pract. 2011;307423. PMID: 21716730       
13. 
Flanagan DF. The effectiveness of articaine in mandibular facial infiltrations. Local Reg 
Anesth. 2016;9:1-6. PMID: 26730209 
14. 
Saxena P, Gupta SK, Newaskar V, Chandra A. Advances in dental local anesthesia 
techniques and devices: An update. J Maxillofacial Surg. 2013;4(1):19-24. PMID: 
24163548                                                                                                        
15. 
Meechan JG. The use of the mandibular infiltration anesthetic technique in adults. J Am 
Dent Assoc. 2011;142(3 Suppl):19-24.  PMID: 21881058                 
16. 
Malamed SF. Is the mandibular nerve block passé? J Am Dent Assoc. 2011;142(9 Suppl):3-
7. PMID: 21881055 
17. 
Gazal G, Fareed WM, Zafar MS. Role of intraseptal anesthesia for pain-free dental treat                     
ment. Saudi Anaesth. 2016;10(1):81-6. PMID: 26955316 
18. 
Heller A.A., Shankland W.E.Alternative to the Inferior Alveolar Nerve Block Anesthesia 
When Placing Mandibular Dental Implants Posterior to the Mental Foramen J Oral 
Implantol.  2001;27(3):127-33. PMID: 12500871 
19. 
Leith R, Lynch K, O'Connell AC. Articaine use in children: a review. Eur Arch Paediatr 
Dent. 2012;13(6):293-6.    PMID: 23235128 
20. 
Gazal G. Comparison of speed of action and injection discomfort of 4% articaine and 2% 
mepivacaine for pulpal anesthesia in mandibular teeth: a randomized, double blind cross-
over trial. Eur J Dent. 2015;9(2):201-6. PMID: 26038650 
21. 
Cowan A. Clinical assessment of a new local anesthetic agent – articaine. Oral Surg Oral 
Med Oral Path. 1977;43(2):174-80. PMID: 264643 
22. 
Srisurang S, Narit L, Prisana P. Clinical efficacy of lidocaine, mepivacaine and articaine 
for local infiltration. J Investig Clin Dent. 2011;2(1):23-8. PMID: 25427324 
23. 
Vree TB, Gielen MJ. Clinical pharmacology and the use of articaine for local and regional 

anaesthesia. Best Pract Res Clin Anaesthesiol. 2005;19:293-308. PMID: 15966499  
24. 
Jastak JT, Yagiela JA. Vasoconstrictors and local anesthesia: a review and rationale for use. 
J Am Dent Assoc. 1988;3:623-30.  PMID: 6355236 
25. 
Leuschner J, Leblanc D. Studies on the toxological profile of the local anaesthetic articaine. 
Arzneim Forschung. 1999;49:126-32.  PMID: 10083981 
26. 
Frenkel G, Aderhold L, Lambrecht JT, Leilich G, Raetzke P. Outpatient oral surgery. Sci 
Dent Tech. Ed. Milan: Edizioni Internazionali srl, Italy,1999. 
27. 
Abazarpoor R, Parirokh M, Nakhaee N, Abbott PV. A comparison of different volumes of 
articaine for inferior alveolar nerve block for molar teeth with symptomatic irreversibile 
pulpitis. J Endod. 2015;41(9):1408-11. PMID: 26149210  
28. 
Mittal M, Sharma S, Kumar A, Chopra R, Srivastava D. Comparison of anesthetic efficacy 
of articaine and lidocaine during primary maxillary molar extractions in children. Pediatr 
Dent 2015;37(7):520-4. PMID: 26883609   
29. 
Di Bella O, Laino L, Mezzogiorno A, Diana DPL, Marino D, Antonucci F, Illiano F, 
Checchi V, Menditti D. Sperimentazione clinica sull’efficacia anestesiologica (profondità 
e reclutamento di fibre nervose) di articaina vs mepivacaina nella chirurgia odontoiatrica 
mandibolare. Giornale Anestesia Stomatologica 2008;35(1-2):39-45. 
30. 
Corbett IP, Kanaa MD, Whitworth JM, Meechan JG. Articaine infiltration anesthesia of 
mandibular first molars. J Endod. 2008;34(5):514-8.  PMID: 18436027 
31. 
Pellicer-Chover H, Cervera-Ballester J, Sanchis-Bielsa JM, Penarrocha-Diago MA, 
Penarrocha-Diago M, Garcia-Mira B. Comparative split-mouth study of anesthetic efficacy 
of 4% articaine versus 0.5% bupivacaine in impacted third molar extraction. J Clin Exp 
Dent. 2013;5(2):e66-71.  PMID: 24455059 
32. 
Ram D, Peretz B. Administering local anaesthesia to paediatric patients: current status and 
prospects for the future. Int J Paediatr Dent. 2002;12(2):80-9. PMID: 11966886  
33. 
Becker DE, Reed KL. Local anesthetics: review of pharmacological considerations. Anesth 

Prog. 2012;59:90-102. PMID: 22822998  
34. 
Vigen EC. Articaine hydrocloride: is it the solution? Dent Update. 2015;42(5):493.  PMID: 
26964452 
35. 
Menditti D, Laino G, Rullo R, Spera M. Association between local anesthetics and 
epinephrine in dental interventions on cardiopathic patients. Rivista Italiana Chirurgia 
Orale 1995;3:45-9. 
36. 
Kämmerer PW, Palarie V, Daubländer M, Bicer C, Shabazfar N, Brüllman D, Al-Nawas B. 
Comparison of 4% articaine with epinephrine (1:100,000) and without epinephrine in 
inferior alveolar block for tooth extraction: double-blind randomized clinical trial of 
anesthetic efficacy. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;113(4):495-9.  
PMID: 22676931 
37. 
Pabst L, Nusstein J, Drum M, Reader A, Beck M. The efficacy of a repeated buccal 
infiltration of articaine in prolonging duration of pulpal anesthesia in the mandibular first 
molar. Anesth Prog. 2009;56:128-34.  PMID: 20020793 
38. 
Bence R. Handbook of clinical endodontics. St Louis: The C.V. Mosby Company;1980. 
39. 
Borchard U. Pharmakologische Aspekte der zahnarztlichen Lokalanasthesie. Der freie 
zahnarzt. 1995;9:58. 
40. 
Dudkiewicz A, Schwartz S, Laliberté R. Effectiveness of mandibular infiltration in 
children using the local anesthetic Ultracaine (articaine hydrochloride). J Can Dent Assoc. 
1987;53:29-31.  PMID: 3545399 
41. 
Tofoli GR, Ramacciato JC, de Oliveira PC, Volpato MC, Groppo FC, Ranali J, et al. 
Comparison of effectiveness of 4% articaine associated with 1:100,000 or 1:200,000 
epinephrine in inferior alveolar nerve block. Anesth Prog. 2003;50:164-8.  PMID: 
14959904 
42. 
Sierra-Rebolledo A, Delgado-Molina E, Berini-Aytis L, Gay- Escoda C. Comparative 
study of the anesthetic efficacy of 4% articaine versus 2% lidocaine in inferior alveolar 

nerve block during surgical extraction of impacted lower third molars.Med Oral Patol Oral 
Cir Bucal. 2007;12:E139-44.  PMID: 17322803 
43. 
Wright GZ, Weinberger SJ, Marti R, Plotzke O. The effectiveness of infiltration anesthesia 
in the mandibular primary molar region. Pediatr Dent. 1991;13(5):278-93.  PMID: 
1815200 
44. 
Ramadurai N, Gurunathan D, Samuel AV, Subramanian E, Rodrigues SJL.Effectiveness of 
2% Articaine as an anesthetic agent in children: randomized controlled trial.Clin Oral 
Investig. 2019;23(9):3543-50.   PMID: 30552590 
45. 
Marino D, Boscolo I, Fabris E, Fontana G, Floreani S, Mazzucchin M, Menditti D, Ruffato 
L, Ruzza C, Zanni B, Bazzato MF, Sivolella S, Zanette G, Berengo M. Anxiolysis and 
treatment of acute postoperative pain in thrid molar extraction. J Dent Anaest. 2004;31:5-
11. 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TABLES 
 
Age of patients (yrs) 
n° of cases 
11-13 
25 
14-15 
15 
15-16 
10 
 
 

 
Table 1. Age distribution of cases. 
 
 
Formulation 
Maximum Dose mg/kg 
(Total) 
Elimination T ½ 
(min) 
Duration of Anesthesia 
Infiltration 
2% Mepivacaine 
1:100.000 epinephrine 
7 (550) 
114 
40-60 min 
4% Articaine 
1:100.000 epinephrine 
5-7 (500) 
20 
60-75 min 
 
 
Table 2. Anesthetics pharmacokinetics parameters. 
 
 
 
Type of anaesthesia 
n° of cases 
(%) 
Mepivacaine 
40 
80 
Articaine 
21 
42 
 
 
Table 3. Request for additional anesthetic injection 
 
 
Tactile-pressure feelings 
after 6-8’ since injection 
(n° of cases) 
(%) 
Intraoperative tactile-
pressure feelings 
(n° of cases) 
(%) Intraoperative 
pain 
 
(n° of cases) 
(%) 
Absent (0) 
20 
40 
12 
24 
 10 
20 
Mild (1) 
10 
20 
8 
16 
9 
18 
Moderate 
(2) 
20 
40 
15 
30 
 15 
30 
Severe (3) 
0 
0 
15 
30 
 16 
32 
 
 
 
 
 
 
Table 4. Mepivacaine-related tactile-pressure and pain feelings 
 
 
 
Tactile-pressure feelings 
after 6-8’ since injection 
(n° of cases) 
(%) 
Intraoperative tactile-
pressure feelings 
(n° of cases) 
(%) Intraoperative 
pain 
 
(n° of cases) 
(%) 

Absent (0) 
35 
70 
43 
86 
45 
90 
Mild (1) 
15 
30 
7 
14 
5 
10 
Moderate 
(2) 
0 
0 
0 
0 
0 
0 
Severe (3) 
0 
0 
0 
0 
0 
0 
 
 
 
Table 5. Articaine-related tactile-pressure and pain feelings 
 
 
Feelings and pain 
Mepivacaine vs 
Articaine 
Absent 
Mild 
Moderate 
Severe 
P-value 
0.048 (*) 
1.000 
0.010 (*) 
0.184 
(*) P < 0.05 
 
 
 
Table 6. Comparison between the patients’ feelings and pain after mepivacaine or articaine 
use.