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ANESTHESIOLOGY
UNCLARITIES ABOUT ARTICAINE: EFFICACY AND THE
Review Articles
RISK OF PARESTHESIA
Nicolas de Ridder1a , Constantinus Politis1b*
1
Department of Oral and Maxillo-Facial Surgery, Faculty of Medicine, Catholic University of Leuven, Leuven, Belgium
MD, Student in Master of Medicine; e-mail: nicolas.deridder@student.kuleuven.be; ORCIDiD: https://orcid.org/0000-0003-1826-8470
a
MD, DDS, MM, MHM, PhD, Professor and Head; e-mail: constantinus.politis@uzleuven.be; ORCIDiD: https://orcid.org/0000-0003-4772-9897
b
ABSTRACT https://doi.org/10.25241/stomaeduj.2020.7(1).art.6
Background Articaine is a very popular local anesthetic in dentistry. A lot of claims have been made about
articaine over the years, both positive and negative. Many clinicians claim articaine is superior to lidocaine.
However, since a study in 1995 claiming an increased risk of paresthesia, there has been debate about
whether this is true or not.
Objective To review the current literature to clarify the current ambiguities about the possible superior
efficacy and the alleged higher risk of paresthesia.
Data sources As a basis, a handbook on local anesthesia was read, as well as its references to the topics
of interest. Afterward, the literature was searched for publications about both the efficacy and the risk of
paresthesia from 1990 to 2019.
Study selection Articles about the efficacy with clear data and minimal risk of bias were selected. For
paresthesia, the original articles were selected as well as more recent reviews highlighting the flaws in the
first studies.
Data extraction Information about the efficacy and the possible superiority of articaine compared to
lidocaine was extracted. For paresthesia, the most important historical publications were reviewed and
more recent reviews were evaluated.
Data synthesis These data were synthesized in an overview consisting of two parts. First, the properties
of articaine were review and what was learned about the efficacy of articaine in relation to other local
anesthetics was discussed. Secondly, an overview of the history of paresthesia was given and the flaws and
unclarities were highlighted.
KEYWORDS
Articaine; Epinephrine; Efficacy; Paresthesia; Dentistry.
1. INTRODUCTION (both good and bad). Some of the good claims
include a supposedly better potency, faster onset of
Articaine is an amide dental local anesthetic, anesthesia and a higher success rate. The bad claim
synthesized in 1969 in Germany. It was specifically is mainly an alleged increased risk of paresthesia.
developed for dental use and got its approval for Some of these claims have been shown to be correct
clinical use in countries all over the world in the (like the success in buccal infiltration anesthesia
years to follow. It became increasingly popular in the adult mandible). However, on a lot of other
and is now the second most used local anesthetic claims or initial reports there is no scientific evidence
in dentistry. Annually, approximately 600,000,000 to prove them or the results are contradictory.
cartridges are manufactured [1]. In 2018 the market
share of articaine was 39,3% in the United States, 2. MATERIALS AND METHODS
and as much as 97% in Germany [1,2]. However,
lidocaine still remains the golden standard for local As background information and the basis of this
anesthesia.Over the years, articaine has been the review, Malamed’s Handbook of Local Anesthesia
subject of intense discussion and (anecdotal) claims (seventh edition) was read. Afterward, searches were
OPEN ACCESS This is an Open Access article under the CC BY-NC 4.0 license.
Peer-Reviewed Article
Citation: de Ridder N, Politis C. Unclarities about articaine: efficacy and the risk of paresthesia. Stoma Edu J. 2020;7(1):44-51.
Received: January 22, 2020; Revised: February 13, 2020; Accepted: February 20, 2020 ; Published: February 22, 2020
*Corresponding author: Professor Constantinus Politis, MD, DDS, MM, MHM, PhD, Head, Department of Oral and Maxillo-Facial Surgery, Faculty of
Medicine, Catholic University of Leuven, Kapucijnenvoer 33, BE-3000, Leuven, Belgium
Tel: / Fax: 0032 (0)16332462
e-mail: constantinus.politis@uzleuven.be
Copyright: © 2020 the Editorial Council for the Stomatology Edu Journal.
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made on PubMed, Trip database and have a maximum recommended dose of 504 mg.
Review Articles
Limo with different combinations of the This equals 7 cartridges. These maximum dosages
following keywords: safety, clinical charac- are well above the dosages normally needed in
teristics, paresthesia, efficacy, lidocaine, articaine, routine dental care (normally a maximum of about
local anesthetics, epinephrine. A selection was made three to four cartridges are needed during routine
of the most relevant articles to make this narrative dental care). With six cartridges you could achieve
review. anesthesia of a full adult mouth [1]. Nevertheless,
exceeding the maximum recommended dose is the
3. CLINICAL CHARACTERISTICS most frequent cause of overdose reactions in dental
patients [1]. That is why it is important to always
Articaine hydrochloride (or 4-methyl-3-[2-(propylamino) calculate this maximum dosage. If used within this
propionamido]-2-hiophenecarboxylic acid methyl range, articaine is a safe drug to use. However, in
ester) is used in dental cartridges of 1.8 mL. These some cases (like certain cardiac patients) a dose
cartridges contain 72 mg of articaine and 0.09 to 0.18 restriction could be advisable to maximize safety,
mg of epinephrine, depending on the concentration as discussed in another review. There are also other
(1:200,000 and 1:100,000 respectively) [1]. important things to remember to safely use dental
local anesthetics and prevent overdose reactions.
3.1. Articaine Basic injection techniques should be applied when
Although it is classified as an amide anesthetic, administering local anesthetics to minimize the
articaine is considered a unique entity within the chance of an overdose reaction. Careful aspiration
amide local anesthetics. It has different properties should be performed prior to every injection to
compared to the other local anesthetics. Most avoid accidental intravascular injection [1]. Further-
importantly, it contains an ester-linkage that can be more, one of the most important factors for over-
hydrolyzed by plasma-esterases and turns articaine dose appears to be the rate of injection: ideally a
in an inactive compound: articainic acid [2]. This rapid cartridge is administered over a period of more than
manner of inactivation is the same biotransformation 60 seconds. A rapid injection (less than 15 seconds)
that occurs in the elimination of ester anesthetics [1]. results in significantly elevated blood levels when
This contributes greatly to the low systemic toxicity accidentally administered intravenously, facilitating
of the drug. This mechanism also gives articaine an overdose reaction [1].
its relatively short elimination half-life of only 27
minutes (compared to 90 minutes for lidocaine) [2]. 3.2. Epinephrine
Secondly, it contains an aromatic thiophene ring Epinephrine is added to the anesthetic solution as a
which would ensure greater lipid solubility. This vasoconstrictor. This has several benefits: First of all,
would increase potency because articaine is better it elicits vasoconstriction in the blood vessels, which
in penetrating tissue and bone [3]. Finally, articaine does not only delay the absorption of the local
has a high degree of protein binding (95%). This anesthetic and thereby decreasing systemic toxicity,
high degree of protein binding may account for a but it also gives hemostasis, less per operative blood
longer duration of anesthetic effect as well for the loss and better visibility. Secondly, it increases the
increased tendency to bind to the protein receptor depth as well as the duration of action of anesthesia,
[1]. Clinically, the drug works by binding reversibly to prolonging and enhancing the anesthetic effect.
the alfa-unit of the voltage-gated sodium channels Because of this, the dose of anesthetic used can
in the nerve, thereby preventing the propagation be reduced [1]. The addition of epinephrine does
of action potentials [3]. This gives pulpal anesthesia have its implications: because of its effects on the
for approximately 60 minutes and soft tissue anes- myocardium and the vascular tone, a dose restriction
thesia for 3 to 5 hours, making articaine an inter- to a maximum of 40 µg per appointment as stated
mediate-acting anesthetic [4]. There is a theory by Bennett and Malamed [2,6]. This equals four
suggesting that local saturation of serum esterases cartridges of epinephrine 1:200,000. The safe
would cause a delay in local metabolism of articaine. use of ≤ 4 cartridges of the higher concentrated
This mechanism would account for the prolonged anesthetic lidocaine (1:100,000 epinephrine) was
anesthetic effect while the systemic toxicity remains recently confirmed in a systematic review [7]. A
low [4]. A study showing high alveolar blood levels lot of the other contra-indications or possible
of articaine post-extraction with an increased interactions in the package leaflet of articaine are
metabolic rate from articaine to articainic acid included because of the addition of epinephrine as
supports these claims [5]. As with all drugs, the well. It should be noted however that the doses of
clinician should be careful not to elicit overdose epinephrine used in dentistry are minimal. One 1.8
reactions by using too much of the drug. Articaine mL of 1:100,000 and 1:200,000 epinephrine contains
has a maximum recommended dose of 7.0 mg/ 0.018 and 0.009 mg respectively. This dose is rather
kg [1]. A cartridge contains 1.8 mL of anesthetic low compared to other uses of epinephrine in
solution, so for articaine 4% it equals 72 mg of medicine (0.3 to 1 mg in case of anaphylactic shock)
articaine. A normal healthy adult of 72 kg would [1]. In these small quantities, the systemic cardio-
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Review Articles Table 1. Successful pulpal anesthesia. Table 2. Onset time of pulpal anesthesia.
Articaine Lidocaine P-value Articaine Lidocaine
onset ±SD onset ±SD P-value
Mandibular (min) (min)
75% 45% 0.0001
second molar
Mandibular
Mandibular first second 4.6 ± 4.0 11.1 ± 9.50 0.0001
87% 57% 0.0001
molar molar
Mandibular Mandibular
92% 67% 0.0001 4.2 ± 3.1 7.7 ± 4.3 0.0002
second premolar first molar
Mandibular first Mandibular
86% 61% 0.0001
premolar second 4.3 ± 2.3 6.9 ± 6.6 0.0014
premolar
Robertson D, Nusstein J, Reader A, Beck M, McCartney M. The anesthetic
efficacy of articaine in buccal infiltration of mandibular posterior teeth. J Am Mandibular
first 4.7 ± 2.4 6.3 ± 3.1 0.0137
Dent Assoc. 2007;138:1104–1112, Table 1 premolar
Robertson D, Nusstein J, Reader A, Beck M, McCartney M. The anesthetic
efficacy of articaine in buccal infiltration of mandibular posterior teeth. J Am
Dent Assoc. 2007;138:1104–1112, Table 2
vascular effects are modest to negligible depending As is turns out, articaine gives the best improvement
on the type of patient [1]. Of course, it should in success rate comparing to lidocaine (55,6% to
be mentioned that in some cases it is not safe to 91,7% for the first molar, 66,7% to 88,9% for the
use articaine (like some refractory unstable heart second molar) [10].
diseases) [1]. However, these are all contraindications
to general elective dental care as well and need 4.2. Conclusion
immediate attention from a medical specialist. A meta-analysis by Katyal in 2010 comparing arti-
caine with lidocaine concluded that articaine has a
4. EFFICACY higher anesthetic success in the posterior first molar
area, while the safety is comparable with lidocaine
There are some reports of clinicians who state that ‘in (RR 1.31, 95% CI of 1.12 to 1.54) [11]. However, the
their opinion’ articaine has a faster onset following variability of anesthetic success of certain techniques
injection. However, in a study comparing the time of and the effect of local inflammation were not taken
onset of pulpal anesthesia after an inferior alveolar into account [4,11]. Yapp provided a comprehensive
nerve block (IANB) between 2% lidocaine and 4% overview of seventeen papers comparing the efficacy
articaine in 1554 patients, these claims were not of articaine [4]. Ten papers found no significant
supported [2]. difference, while 7 papers did find an advantage
It has also been claimed that articaine may provide for articaine (however each review investigated
palatal anesthesia when given as maxillary buccal different clinical situations) [4]. As a conclusion, the
infiltration [1]. Although this claim is anecdotal, it overall efficacy of articaine is similar to lidocaine. For
could be attributed to the greater lipid solubility. mandibular infiltrations, mental nerve blocks and a
buccal infiltration following an IANB, articaine does
4.1. Mandibular infiltration appear to have a significant advantage [4]. Paxton
A claim that has been shown to be true is the and Thome reviewed all 27 publications until 2010
significant success of articaine used by buccal reporting on the efficacy of articaine [12]. These
infiltration in the mandible. publications showed a variability of outcomes,
When articaine was used for mandibular infiltration but nevertheless their meta-analysis did show a
in adults, it has been proven that the chances of significant difference (9.21% higher proportion of
success are significantly greater in comparison to success, 95% CI 2.56% to 15.58%) [2]. This suggested
lidocaine (see Table 1) [8]. an advantage for articaine, at least in some clini-
The time of onset for pulpal anesthesia was also cal situations [13]. Furthermore, articaine was com-
significantly shorter for articaine in the first and pared with 1:100,000 and 1:200,000 epinephrine
second molar, and the first premolar (see Table 2) [8]. concentrations and no significant difference was
Another study found similar results concerning found [12]. However, it should be noted that all these
the mandibular incisor: Both the duration and the studies are only low to moderate-quality evidence
success rate of pulpal anesthesia was considerably so conclusions must be critically reviewed.
longer with the articaine solution [9].
The reason for this increased success rate could be 5. PARESTHESIA
the relatively thin cortical plate, subject to the potent
penetrating capability of articaine [2]. Local anesthetics are used to achieve anesthesia in
Kanaa et al. did research on the addition of articaine the desired area to perform a pain-free procedure.
or lidocaine infiltration to improve the success rate Normally this anesthesia wears off in a matter of
of anesthesia following an IANB [10]. hours, but there have been reports of paresthesia
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Review Articles
Table 3. Risk of paresthesia from local anesthetic drugs. Table 4. Relative risks of paresthesia in Ontario, Canada and the
United States.
2007 2012 Result
Ontario, Canada United States
<1.0, less than
Lidocaine 0.64 0.5 Mepivacaine 1 : 1,250,000 1 : 623,112,900
expected
Lidocaine 1 : 1,125,000 1 : 181,076,673
Articaine 1.19 0.97 ~1, expected
Bupivacaine NA 1 : 123,286,050
>1.5, higher than Overall risk 1 : 785,000 1 : 13,800,970
Mepivacaine NA 2.2 expected Articaine 1 : 440,000 1 : 4,159,848
>3.0, higher than Prilocaine 1 : 588,000 1 : 2,070,678
Prilocaine 4.96 3.25 expected Malamed SF. Articaine 30 years later. Oral Health. 2016; Table 8
The ratio derived from the percentage of reported cases of paresthesia divided
the percent market share of the drug.
Malamed SF. Articaine 30 years later. Oral Health. 2016; Table 9
There have been studies reporting a higher incidence in Denmark, that a local anesthetic, articaine, was
of paresthesia with the use of 4% local anesthetics responsible for an increased risk of nerve injuries
like prilocaine and articaine. An overview of the compared with the risk associated with other local
history of this controversy is given below. anesthetics (mepivacaine, prilocaine, lidocaine)”
[15]. The report concluded: “Regarding articaine,
5.1. History the conclusion is that [the] safety profile of the drug
Everything started with a retrospective study by Haas has not significantly evolved since its initial launch
and Lennon in 1995 [13]. They examined voluntary (1999 in Denmark). Thus, no medical evidence exists
submissions that dentists made to their insurance to prohibit the use of articaine according to the
agency. They found 143 cases of paresthesia over current guidelines listed in the summary of product
a 20-year period (1973 to 1993), excluding those characteristics” [15]. “All local anesthetics may cause
associated with surgery [13]. The paresthesia involved nerve injury (they are neurotoxins). The occurrence
the lingual nerve, the inferior alveolar nerve or a of sensory impairment is apparently slightly more
combination of both [13]. Based on the distribution frequent following use of articaine and prilocaine.
of the market share of local anesthetics in Ontario in However, considering the number of patients treated,
1993, articaine and prilocaine had a relatively higher sensory impairments rarely occur. For example, the
risk of developing paresthesia [13]. In 1993, 10 of the incidence of sensory impairment following the use
14 reports of paresthesia were related to articaine, of articaine is estimated to be 1 case in 4.6 million
the other 4 to prilocaine. This equals an overall treated patients” [2,15]. Furthermore, they reported
risk of 1:785,000. The individual rates reported for that there are different incidents that can result in a
articaine (1:588,235) and prilocaine (1:440,529) nerve injury: mechanical injury due to needle trauma,
were a lot higher than the other anesthetics direct drug toxicity or neural ischemia for example
(1:1,250,000) [13]. Almost all of the forthcoming [15]. The Danish Medicines Agency followed up
papers claiming an increased risk of paresthesia with this study in October 2011 (117/43) [16]. Their
refer to this paper as the original source. Hillerup database of side effects comprised 160 reports of
and Jensen conducted a study (2006) reviewing adverse reactions related to articaine between 2001-
insurance claims in Denmark, where articaine was 2005, most of which concerning nerve damage [16].
introduced in 2001 [14]. They claimed that articaine However, since 2005 they have observed a drop
had a higher tendency to cause paresthesia as it was in the number of new adverse reaction reports.
most reported to the Danish Medicines Agency by For 2011, up until the first of October they only
dentists [14]. They declared that articaine should received 2 reports of possible sensory impairment
not be the anesthetic of choice when administering [16]. This drop in the number of adverse effects can
an IANB until factual information is available, a be explained by two phenomena: the Weber Effect
statement consequentially recommended by the and the effect of publicity on drug prescription and
Danish Dental Association as well [14]. In this usage [2]. Both phenomena will be clarified later.
review, 77% of the cases reviewed involved only the Pogrel also wrote some interesting papers about
lingual nerve, and not the inferior alveolar nerve articaine over the years [17–21]. In a 2007 paper,
[14]. In response, the Pharmacovigilance Working Pogrel investigated 57 nonsurgical cases of
Committee of the European Union reviewed arti- paresthesia following local anesthetic administration
caine use in 57 different countries addressing the from 2003 to 2005 [16,17]. His update on this paper
controversy about paresthesia [15]. They estimated in 2012 reported on an additional 41 cases from
the number of patients receiving articaine is around 2006 to 2011 [18]. In both reviews, Pogrel compared
100 million annually [15]. In October 2006 they the percentage of the market share of the local
published the following report: “This investigation anesthetic to the proportion of the incidences of
is a follow-up to an inquiry initiated in 2005. This paresthesia reports [17,18]. Articaine had a ratio of
enquiry resulted from suspicions that were raised 1.19 in 2007 and 0.98 in 2012 [17,18]. Lidocaine did
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Review Articles Table 5. Reports of paresthesia following local anesthesia with the most
common local anesthetics.
Table 6. Lingual nerve involvement in reported cases of paresthesia.
Cases of Lingual
All ADRs
paresthesia Nerve
Authors Country Year Involvement
Lidocaine 247 7,720 (%)
Bupivacaine 99 2,843 Haas and Canada 1995 70.6
Articaine 85 254 Lennon14
Combinations of Hillerup and Denmark 2006 77.0
45 2,687 Jensen15
local anesthesia
24
Prilocaine 30 396 Garisto et al. United States 2010 92.7
23
Other 67 4,647 Kingon et al. Australia 2011 80.0
Total 573 18,574 Malamed SF. Articaine 30 years later. Oral Health. 2016; Table 8
ADR: Adverse drug reactions
Piccinni C, Gissi DB, Gabusi A, Montebugnoli L, Poluzzi E. Paraesthesia after Lo-
cal Anaesthetics: An Analysis of Reports to the FDA Adverse Event Reporting
System. Basic and Clinical Pharmacology and Toxicology. 2015; Table 2
better than expected an only had a ratio of 0.64 in about the studies performed. What is the rationale
2007 and 0.5 in 2012 [18]. The results are shown in behind the fact that the vast majority of paresthesias
table 3 (see Table 3) [2,17,18]. Following these results, occurs after an IANB? Less than 5% of the cases
Pogrel concluded that there is no disproportionate involve the maxilla, while roughly half of the dental
nerve involvement for articaine [22]. Prilocaine, work is in the maxilla [2]. Why are these cases of
however, does show a higher incidence (ratio 4.96 paresthesia rather specific to the use of an IANB
and 2.2 in 2007 and 2012 respectively) [22]. One of and not with alternative nerve blocks (like Gow-
the points of criticism noted in this paper is that in the Gates) [2]. Why are there no similar reported toxicity
reports to outside agencies there is no mentioning cases with articaine use in the other branches of
whether the paresthesia was transient or permanent medicine (plastic surgery, dermatology, …) [3].
(as most of the paresthesias eventually recover) [23]. Some elements concerning the hypothesis of the
The Australian regulatory body issued a warning neurotoxicity as the cause of the cases of paresthesia
statement against articaine as well following a remain unexplained. As seen in the previous papers
2011 paper by Kingon discussing 5 case reports of the vast majority of cases of paresthesia involved
paresthesia following local anesthetic administration the lingual nerve, in the Garisto paper even 89%
[22]. However, in 2 of these cases, the only thing the involved exclusively the lingual nerve (see Table 6)
patient experienced was an ‘electric shock’ with [2,13,14,22,23]. If neurotoxicity caused paresthesia
the injection [22]. Garisto conducted research in we would expect the inferior alveolar nerve to
the United States in July 2010 with data gathered be involved much more commonly. Opening the
from the US Food and Drug Administration (FDA) mouth to deposit the cartridge could stretch out the
Adverse Event Reporting System (AERS) between lingual nerve, preventing it from being pushed away
1997 and 2008 [23]. From the 248 cases, of which by the needle and being damaged [2]. In another
94.5% happened as a result of an IANB, there was as paper, he explained this discrepancy could be
much as 89% that exclusively involved the lingual partially explained by the fact that the lingual nerve
nerve [23]. Of these 248 cases, 108 resolved in a only consists of one to three fascicles, while the IAN
time period between 1 to 736 days [23]. In this study consists of five to seven fascicles [21]. The claim of
Garisto compared the incidences with the paper of a possible higher intrinsic toxicity of articaine 4%
Haas and Lennon (1995): It appears the difference in compared to lidocaine 2%, which could possibly
incidence is more than a tenfold (see Table 4) [13,24]. explain a higher incidence of paresthesia, was not
It is noteworthy that the FDA website for AERS warns supported in in-vitro investigations [26]. While some
that the AERS data has limitations: Reports do not remain believing in the intrinsic higher neurotoxicity
require to prove a causal relationship, reports do not of the 4% anesthetics, others believe there are factors
always contain enough detail and not all adverse usually involved to cause the paresthesia (primarily
events are reported [24]. Therefore, they state that mechanical trauma) [1]. There are a lot of different
AERS cannot be used to calculate incidences for the ways nerve paresthesia could be explained: Trauma
US population [24]. Another study analyzed the data by contact of the nerve sheath with the needle,
of the AERS in the United States from 2005-2011. 573 hemorrhage into or around the neural sheath as the
cases of paresthesia were identified out of the 18,574 pressure on the nerve will increase, edema following
reports [25]. Table 5 gives an overview of the reports surgical procedures[1]. Keep in mind that one does
for the most common anesthetics (see Table 5). not exclude the other. Next, focus will be on the
Weber Effect and the effect of publicity. The Weber
5.2. Unclarities Effect is an epidemiological event that constitutes a
There are numerous comments or thoughts to be rise in reporting of adverse events after its regulatory
made about the controversy about paresthesia and approval, with a peak at the end of its second year
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advantages in comparison to other local anesthetics,
Review Articles
there is no conclusive evidence demonstrating
neurotoxicity or significantly superior anesthetic
properties of articaine for dental procedures” [4].
Van der Sleen evaluated 1000 patients receiving an
IANB, and concluded that no long-term injury will
be caused as long as the mandibular nerve is not
manipulated [29]. When applying a local anesthetic
would result in paresthesia, these are only temporary
and the cause remains unknown [29]. The most
common cause of nerve injury remains mechanical
trauma like surgery or third molar extractions.
Malamed makes the following recommendation:
Figure 1. Articaine use and reports of paresthesia (Denmark). For the administration of an IANB you can continue
Malamed SF. Handbook of Local Anesthesia. 7th ed. St Louis: Mosby; 2019, to use articaine 4% with epinephrine 1:100,000 or
Figure 20.9
1:200,000, provided you use the correct injection
(see Fig. 1) [1,2]. Afterward, the reports steadily techniques [2]. If, however, the practitioner is not
decline while prescribing rates keep rising steadily convinced by the absence of scientific evidence
[2]. This is a replicable and verified phenomenon or still concerned, an alternative could be to use
[27]. Publicity (whether positive or negative) lidocaine 2% with epinephrine 1:100,000 followed
affects how much drugs are used and prescribed by infiltration anesthesia with articaine in the desired
[2]. Implemented on this debate, we conclude that area to improve effectiveness [2].
indeed the use of articaine decreased after the
paper of Hillerup and the recommendation of the 6. DISCUSSION
Danish Dental Association [2]. After the EU report
explaining there was no significant evidence, the use In the early days of the drug, there were a lot of
increased again [2]. Another potential confounder anecdotal claims that articaine would function faster
might be the age of the dentist, as more numerous and better than other anesthetics. Different meta-
younger, inexperienced dentists use articaine as an analyses confirmed that the safety profile of articaine
anesthetic [26]. The last remark is the inconsistency is similar to that of lidocaine [9,10]. In certain clinical
of the reported risks on paresthesia. As already situations, articaine does have a significant advantage
mentioned, the variation between the reported risks over lidocaine (mainly for infiltration anesthesia in the
is tremendous, pleading there must be some kind posterior mandibula) [4,11,12]. However, there is no
of bias. In his 2000 paper, Pogrel estimated the risk convincing evidence to suggest that articaine has an
of permanent nerve damage following an IANB at overall superiority in efficacy over lidocaine. In 1995
1 in 26,762 injections [19]. Therefore, he stated that a retrospective study about paresthesia occurrence
a dentist would reasonably encounter at least one after the administration of local anesthetics started
case in their career [19]. For a risk of 1 in 785,000 as a controversial debate whether or not articaine
mentioned in the Ontario paper however, this would causes more paresthesias than lidocaine [11]. In the
mean a practitioner would encounter a paresthesia following years, numerous papers were published,
once every 436 years (averaging 1,800 injections and different recommendations were sent out by
every year) [28]. Another overall incidence reported different regulatory bodies. All these reports on
is 1:13,800,970 in the US [2]. To put these risks into the alleged higher incidence by articaine show
perspective: the risk of being struck by lightning in contradictory results, widely varying incidences, and
a given year in the US is between 1 in 328,000 and 1 incomplete or biased data. Malamed, well-known in
in 700,000 [1]. matters related to local anesthesia and a proponent
of articaine, wrote an interesting overview of the
5.3. Conclusion subject [4,11,12]. Whether negative or positive,
The studies reporting an increased risk of most of the time one single author is proclaiming
paresthesia contain a lot of bias: The total duration his/her own beliefs without high-quality clinical
of paresthesia, the injection technique, the size of evidence like a randomized controlled trial or a
the needle and even the anesthetic used (in 30% proper meta-analysis to back it up. Because of the
of the incidents reported) are examples of data rarity of the complication, an RCT would require
that are not always documented in these papers too large of a sample size. In 2006 the European
[28]. A 2011 review by Yapp highlights the flaws in Pharmacovigilance System concluded there was
studies concerning articaine: All studies reporting an no scientific or clinical evidence of a greater risk
increased risk contain bias in data recruitment and associated with articaine after examining all
are retrospective [4]. They are not suitable for a strong available clinical data from the Septodont database
recommendation [4]. He concluded that “although [2]. The Danish authorities confirmed these conclu-
there may be controversy regarding its safety and sions after reevaluation in 2012 [2]. Up until now,
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there is no conclusive evidence that articaine would tor for paresthesia is still mechanical violation during
Review Articles
cause a larger number of paresthesias in proportion surgery or tooth extractions. The lingual nerve is
to its market share [2]. most frequently affected rather than the inferior
alveolar nerve due to its anatomy. It should be
7. CONCLUSION kept in mind that a sensory disturbance after local
anesthetic use in non-surgical cases still remains an
Investigations on the superiority of articaine extremely rare event.
showed an advantage over lidocaine in certain situ-
ations (like infiltration anesthesia in the posterior CONFLICT OF INTEREST
mandible). There is insufficient evidence to state
that articaine has an overall superiority to lidocaine. The authors declare no conflict of interest.
Due to the lack of conclusive evidence, the choice
of local anesthetic should be purely based on the FUNDING
practitioner’s experience and personal preference.
Concerning the topic of paresthesia, there exists no This article did not require funding.
scientific evidence proving the alleged higher risk of
articaine on paresthesia. The available research on ACKNOWLEDGMENTS
the matter predominantly comprises the convictions
of one single author, whether positive or negative, This study was conducted as a master thesis to acquire the degree
without high-quality evidence. The main causal fac- of master in medicine at the Catholic University of Leuven.
REFERENCES
1. Malamed SF. Handbook of local anesthesia . Seventh edition. St. 15. Stenver DI, Case number: 3200-1367, Adverse effects from
Louis, MO: Elsevier Inc; 2020. anaesthetics used in relation with dental care with a special focus
2. Malamed SF. Articaine 30 years later. Oral Health. [Internet] 2016. on anaesthetics containing articaine. Pharmacovigilance Working
[Full text links] Party of the European Union. 20 October, 2006.
3.Snoeck M. Articaine: a review of its use for local and regional 16. Danish Medicines Agency (Laegemiddel Styrelsen), Report 25
anesthesia. Local Reg Anesth. 2012;5:23-33. October 2011.
[Full text links] [CrossRef ] [PubMed] Google Scholar Scopus 17. Pogrel MA. Permanent nerve damage from inferior alveolar
4.Yapp KE, Hopcraft MS, Parashos P. Articaine: a review of the nerve blocks - an update to include articaine. J Calif Dent Assoc.
literature. Br Dent J. 2011;210(7):323-329. 2007;35(4):271-273.
[Full text link] [CrossRef ] [PubMed] Google Scholar [Full text link] [PubMed] Google Scholar Scopus
5.Oertel R, Richter K, Weile K, et al. A simple method for the 18. Pogrel MA. Permanent nerve damage from inferior alveolar nerve
determination of articaine and its metabolite articainic acid in blocks: a current update. J Calif Dent Assoc. 2012;40(10):795-797.
dentistry: Application to a comparison of articaine and lidocaine [Full text link] [CrossRef ] [PubMed] Google Scholar Scopus
concentrations in alveolus blood. Methods Find Exp Clin Pharmacol. 19. Pogrel MA, Thamby S. Permanent nerve involvement resulting
1993;15(8):541-547. from inferior alveolar nerve blocks [published correction
[PubMed] Google Scholar Scopus appears in J Am Dent Assoc. 2000;131(10):1418]. J Am Dent Assoc.
6. Bennett CR. Monheim’s local anesthesia and pain control in dental 2000;131(7):901-907.
practice, 7th edition. St. Louis, MO: CV Mosby; 1984. [Full text link] [PubMed] Google Scholar Scopus
7. Godzieba A, Smektała T, Jędrzejewski M, Sporniak-Tutak K. Clinical 20. Pogrel MA, Thamby S. The etiology of altered sensation in the
assessment of the safe use local anaesthesia with vasoconstrictor inferior alveolar, lingual, and mental nerves as a result of dental
agents in cardiovascular compromised patients: a systematic treatment. J Calif Dent Assoc. 1999;27(7):531-538. [PubMed]
review. Med Sci Monit. 2014;20:393-398. doi: 10.12659/MSM.889984 Google Scholar Scopus
[Full text links] [PubMed] Google Scholar Scopus 21. Pogrel MA, Schmidt BL, Sambajon V, Jordan RCK. Lingual
8. Robertson D, Nusstein J, Reader A, et al. The anesthetic efficacy nerve damage due to inferior alveolar nerve blocks: a
of articaine in buccal infiltration of mandibular posterior teeth. J possible explanation. J Am Dent Assoc. 2003;134(2):195-199.
Am Dent Assoc. 2007 Aug;138(8):1104-1112; [Full text link] [CrossRef ] [PubMed] Google Scholar Scopus
[Full text link] [PubMed] Google Scholar Scopus 22. Kingon A, Sambrook P, Goss A. Higher concentration local
9. Meechan JG, Ledvinka JIM. Pulpal anaesthesia for mandibular anaesthetics causing prolonged anaesthesia. Do they? A literature
central incisor teeth: A comparison of infiltration and review and case reports. Aust Dent J. 2011;56(4):348-351.
intraligamentary injections. Int Endod J. 2002;35(7):629-634. [Full text link] [CrossRef ] [PubMed] Google Scholar
[Full text link] [CrossRef ] [PubMed] Google Scholar Scopus 23. Garisto GA, Gaffen AS, Lawrence HP, et al. Occurrence of
10. Kanaa MD, Whitworth JM, Corbett IP, Meechan JG. Articaine paresthesia after dental local anesthetic administration in the
buccal infiltration enhances the effectiveness of lidocaine United States [published correction appears in J Am Dent Assoc.
inferior alveolar nerve block. Int Endod J. 2009;42(3):238-246. 2010;141(8):944]. J Am Dent Assoc. 2010;141(7):836-844.
[Full text link] [CrossRef ] [PubMed] Google Scholar Scopus [Full text link] [CrossRef ] [PubMed] Google Scholar Scopus
11. Katyal V. The efficacy and safety of articaine versus lignocaine 24. U.S. Food and Drug Administration Center for Drug
in dental treatments: A meta-analysis. J Dent. 2010;38(4):307-317. Evaluation and Research, Office of Post-Marketing Drug Risk
[Full text link] [CrossRef ] [PubMed] Google Scholar Scopus Assessment. Revised 9 January 2009. http://www.fda.gov/Drugs/
12. Paxton K, Thome DE. Efficacy of articaine formulations: GuidanceComplianceRegulatoryInformation/Surveillance/
quantitative reviews. Dent Clin North Am. 2010;54(4):643-653. AdverseDrugEffects/default.htm.
[Full text link] [CrossRef ] [PubMed] Google Scholar Scopus 25. Piccinni C, Gissi DB, Gabusi A, et al. Paraesthesia after local
13. Haas DA, Lennon D. A 21 year retrospective study of reports of anaesthetics: an analysis of reports to the FDA Adverse Event
paresthesia following local anesthetic administration. J Can Dent Reporting System. Basic Clin Pharmacol Toxicol. 2015;117(1):52-56.
Assoc. 1995;61(4):319-330. [Full text link] [CrossRef ] [PubMed] Google Scholar Scopus
[PubMed] Google Scholar Scopus 26. Hopman AJG, Baart JA, Brand HS. Articaine and
14. Hillerup S, Jensen R. Nerve injury caused by mandibular block neurotoxicity - a review. Br Dent J. 2017;223(7):501-506.
analgesia. Int J Oral Maxillofac Surg. 2006;35(5):437-443. [Full text link] [CrossRef ] [PubMed] Google Scholar Scopus
[Full text link] [CrossRef ] [PubMed] Google Scholar Scopus
50 Stoma Edu J. 2020;7(1):44-51 pISSN 2360-2406; eISSN 2502-0285
Articaine: Efficacy and the risk of paresthesia
www.stomaeduj.com
27. Hartnell NR, Wilson JP. Replication of the Weber effect using 29. van der Sleen JM, Jaspers GW, de Lange J. Trigeminal
Review Articles
postmarketing adverse event reports voluntarily submitted to the nerve paraesthesia from inferior alveolar nerve blocks:
United States Food and Drug Administration. Pharmacotherapy. incidence and course. Oral Surg. 2015;8(4):217-220.
2004;24(6):743–749. [Full text link] [CrossRef ] Google Scholar Scopus
[Full text link] [CrossRef ] [PubMed] Google Scholar Scopus
28. Diaz M. Is it safe to use Articaine? TeamWork. 2009;2(2):28-35.
doi: 10.14219/jada.archive.2001.0152
[Full text link] [PubMed] Google Scholar
Nicolas de RIDDER
MD, Student in Master of Medicine
Department of Oral and Maxillo-Facial Surgery
Faculty of Medicine
Catholic University of Leuven
Leuven, Belgium
CV
Nicolas De Ridder (DOB: 28th of May, 1996) obtained his bachelor’s degree in Medicine at the Catholic University of Leuven,
Belgium (magna cum laude). He is currently in his final year of master in Medicine, expected to graduate in July 2020. He has
acquired experience in internships in the department of Stomatology, Oral and Maxillofacial surgery under the supervision of
Professor Constantinus Politis at UZ Leuven.
Questions
1. What is the most common cause of overdose reactions or complications in dental
treatment with local anesthetics?
qa. Using an excessive total dose of the drug;
qb. Not complying with the listed contraindications;
qc. Use in children;
qd. Use in cardiovascular compromised patients.
2. What is true about the efficacy of articaine compared to lidocaine?
qa. Articaine is overall the superior local anesthetic;
qb. The efficacy of articaine is similar to that of lidocaine, with an advantage in certain clinical situations;
qc. Articaine is an inferior local anesthetic compared to lidocaine;
qd. Articaine is a better local anesthetic than lidocaine, but it is not worth the benefit because of its higher
risks.
3. Which of the following statements concerning the pharmacological properties about
articaine is not true?
qa. Articaine has a shorter elimintation half-life than most other local anesthetics;
qb. Articaine has a thiophene ring ensuring greater lipid solubility;
qc. Articaine contains an ester-linkage that can be hydrolyzed by plasma-esterase, making it a hybrid
molecule;
qd. Articaine has a low degree of protein-binding, just as most other local anesthetics.
4. The incidence of paresthesia for articaine is:
qa. Significantly lower than lidocaine;
qb. In relation to its market share;
qc. Higher than prilocaine;
qd. Higher than its market share.
Stoma Edu J. 2020;7(1): 44-51 pISSN 2360-2406; eISSN 2502-0285 51