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Articaine use in children: a review.

Introduction

Local analgesia can be one of the most challenging aspects of paediatric dentistry. An ideal agent should provide maximum efficacy using a minimum number of injections while causing negligible adverse effects. While lidocaine has been the gold standard local analgesia agent for the past 50 years, the search for a more effective agent has continued. Articaine was developed in Germany in the early 1970s, but its use in Ireland and the UK only came to the fore in 2006 during a shortage in supply of lidocaine. Since then articaine has become increasingly popular for adult dentistry, however an uncertainty exists among dentists regarding the safety of articaine in children. Although the safety and efficacy of articaine has been proven and it is reported to be comparable [Malamed et al., 2000a] or superior to lidocaine [Brandt et al., 2011], a survey of American general and paediatric dentists found that the majority of respondents still prefer lidocaine for use in children [Brickhouse et al., 2008].

How is articaine different? Articaine hydrochloride is an amide type local analgesia [Malamed, 1997]. It acts in a similar way to other amide analgesia but its unique chemical structure offers advantages over traditional amide analgesias. Articaine contains a thiophene ring which makes it more potent and more lipid-soluble, thereby enabling it to diffuse more readily through both hard and soft tissue. In addition, articaine has a high affinity for plasma protein binding and it is the only amide analgesia to contain an ester group; this allows it to be rapidly broken down into its inactive state, thus decreasing systemic toxicity [Malamed et al., 2000a; Oertel et al., 1997]. Articaine is manufactured as a 4% solution with 1:100,000 or 1:200,000 adrenaline in 2.2ml and 1.7ml glass dental cartridges. Both concentrations impart a rapid onset of analgesia and a similar degree of pulpal (approximately 1 hour) and soft tissue analgesia (3-5 hours) [Malamed et al., 2000a].

Is articaine safe to use in children? Articaine 4% 1:100,000 is reported to be a well-tolerated, safe and effective local analgesia for use in children [Dudkiewicz et al.,1987; Wright et al., 1989; Malamed et al., 2000a; Malamed et al., 2001; Ram and Amir, 2006; Adewumi et al., 2008; Katyal at el., 2010]. Articaine is 1.5 times as potent as lidocaine [Wright et al., 1989; Malamed, 1997] so administration uses a smaller volume of solution but a higher concentration of drug. This reduced volume may be of value in decreasing the discomfort of analgesia administration, particularly where co-operation in children is inadequate. Wright specifically investigated the use of articaine in paediatric dental patients less than 4 years of age with promising results [Wright et al., 1989], however the manufacturers still do not recommend it for children younger than 4 years. A recent systemic review had to conclude that there was insufficient data to support use of articaine in very young children [Katyal et al., 2010]. Precautions when using articaine are similar to those when using other amide products, specifically in children under 4 years of age. As with all medication, dosage should be calibrated on a mg/kg basis for children. Metabolism of articaine is age dependent and the clearance and volume of distribution decreases with increasing age [Oertal et al., 1999]. Due to these age related differences in pharmacokinetics, it has been reported that there is no need to fix a lower mg/kg articaine dose limit for children [Jakobs et al., 1995]. The current child dosage recommendation for articaine is 7mg/kg (Table 1); however some authors have advocated a lower limit of <5mg/kg for children aged 4-12 years, especially if used in conjunction with sedative agents [Wright et al., 1989]. In any case, while smaller volumes of articaine can be administered it must be remembered that the concentration of articaine is twice that of lidocaine so that the safe number of cartridges must be halved (Table 1). This maximal dosage could easily be exceeded if dentists are not vigilant in children.

Overall, the evidence suggests that articaine administration leads to few adverse events [Dudkiewicz et al., 1987; Wright et al., 1989; Ram and Amir, 2006], and is comparable to lidocaine in this respect [Malamed et al., 2000b; Malamed et al., 2001; Ram and Amir, 2006; Katyal, 2010] (Table 2). Allergy to local analgesia is uncommon and a patient allergic to articaine would likely have a similar allergy to other amide analgesia including lidocaine [Malamed et al., 2001]. Prolonged numbness has been reported as the most common adverse effect following articaine injection, particularly in children younger than 7 years [Adewumi et al., 2008]. Accidental injury to anaesthetised lips have been reported in about 2% of cases [Malamed et al., 2000b]. Adewumi and co-workers [2008] reported that when using articaine, 40% of children experience numbness for 3 hours and 11% for 5 hours, and this prolonged numbness can induce anxiety. Interestingly, there was no association between prolonged numbness and the site or amount of articaine administered. Similarly, Ram and Amir [2006] found the duration of soft tissue numbness following articaine injection was greater than that for lidocaine (3.43 [+ or -] 0.7 vs. 3.0 [+ or -] 0.8 hours). More recently, a randomised double blind study reported that articaine had a longer duration of soft tissue numbness than mepivacaine (140.69 +/- 49.76 versus 117.52 +/- 42.99 minutes) [Odabas et al., 2012]. Given the evidence presented above, parents of paediatric patients must be warned of the risk of self-inflicted soft tissue injury following use of articaine.

How effective is articaine compared to other analgesia in children? While the majority of the literature focuses on the use of articaine in adult populations, a few studies have investigated the efficacy and safety of articaine following use in children (Table 2). Malamed compared pain control achieved when using 4% articaine and 2% lidocaine in patients for simple and complex dental procedures [Malamed et al., 2000a]. When patients scored their perceived pain using a visual analogue scale (VAS), articaine was found to have a lower score for both simple and complex dental procedures indicating a more profound level of analgesia. Mikesell and colleagues reported that articaine achieved pulpal analgesia in 4-54% of cases compared to 2-48% for lidocaine following inferior alveolar nerve blocks (IANB) in patients of varying age ranges, although this difference was not significant [Mikesell et al., 2005]. Two recent meta-analyses comparing 4% articaine to 2% lidocaine provide strong evidence that articaine provides superior analgesia success [Brandt et al., 2011; Katyal, 2010]. Using successful pulpal analgesia in teeth with irreversible pulpitis as an outcome measure, Brandt concluded that articaine produced successful analgesia 2.44 times more often than lidocaine and was 3.81 times more effective when using an infiltration technique [Brandt et al., 2011]. Katyal investigated analgesia for patients requiring a wider range of dental treatments and concluded that articaine achieved analgesia of mandibular first permanent molars (FPM) 1.31 times that achieved with lidocaine [Katyal, 2010]. A comparison of articaine to analgesias other than lidocaine suggested no difference in the analgesia efficacy of 4% articaine 1:200,000 with 3% mepivacaine in 50 children aged 7-13 years [Odabas et al., 2012]. A study comparing articaine and prilocaine found that maxillary infiltration with prilocaine caused almost twice as many positive pain reactions than infiltration with articaine [Yilmaz et al., 2011]. In addition, using pain related behaviour scores to determine analgesia efficacy, articaine was found to be more effective than prilocaine during removal of coronal pulp yet the frequency of adverse events was similar for both analgesias. In summary, there is evidence that 4% articaine is comparable to or more efficacious than other analgesia agents used in children.

What about using articaine for mandibular block analgesia? The reluctance to use articaine for IANB in dentistry arose following initial reports of prolonged sensory disturbances with articaine use [Hass and Lennon, 1995]. The incidence of adverse drug reactions is similar among all local analgesia agents [Malamed et al., 2001] and most commonly occur due to accidental intravascular administration of LA solution or direct trauma to the tissues. Iatrogenic nerve damage following IANB is estimated to occur in about 1:500,000 blocks, with the lingual nerve more commonly affected and little information on the analgesia used [Meecham, 2009]. Hass and Lennon [1995] reported that nerve damage was more common using a 4% analgesia agent like articaine compared to a 2% solution, although it has been suggested that over-reporting of such injuries are more likely when a new drug is introduced [Meecham, 2009]. Recent reports suggest that there is no difference in the incidence of paraesthesia following IANB using lidocaine or articaine [Mikesell et al., 2005; Pogrel, 2007]. Pogrel suggested that there was no increased risk of inferior alveolar nerve damage using articaine and adverse effects were reported in proportion to its usage [Pogrel, 2007].

Can articaine infiltration replace an IANB? Infiltration with articaine is more effective than infiltration with lidocaine for anaesthetising the mandibular FPM area in adults [Robertson et al., 2007; Katyal, 2010; Brandt et al., 2011]. Existing evidence also indicates that IANB with articaine is equivalent to IANB with lidocaine [Mikesell et al., 2005]. Where a lidocaine IANB produces inadequate analgesia, it has been shown that supplemental buccal infiltration with articaine increases success [Kanaa et al., 2006; Hasse et al., 2008 and 2009]. Therefore, if added analgesia is required following an IANB with lidocaine, articaine should be used.

Buccal infiltration with 4% articaine is equally effective as articaine IANB in anaesthetising mandibular molars with irreversible pulpitis [Poorni et al., 2011]. As there is no significant difference in successful pulpal analgesia, there is no benefit in using articaine as an IANB [Meecham, 2009]. Furthermore, more successful mandibular FPM analgesia has been reported following using buccal infiltration with articaine (70.4%) compared to lidocaine IANB (55.6%) [Corbett et al., 2008]. Therefore, there is evidence to suggest that IANB with lidocaine can be substituted by buccal infiltrations with articaine. However further paediatric specific studies are required to verify this finding in adults.

Are there other advantages of using articaine in children?

Avoidance of an IANB in children has advantages. Pain control for pulp therapy and extractions of primary molars can be successfully achieved with articaine infiltration alone. The avoidance of an IANB in children eliminates the risk of inferior alveolar and lingual nerve damage. Replacement of IANB injections of lidocaine with buccal infiltrations of articaine will reduce the extent of soft tissue analgesia experienced by the patient, thus eliminating the poorly tolerated experience of lingual nerve analgesia. Teeth with molar incisor hypomineralisation (MIH) can be difficult to anaesthetise adequately, and in the author's experience buccal infiltration with articaine appears to offer superior analgesia.

In adults, palatal diffusion occurs when articaine is administered as a buccal infiltration in the maxilla [Uckan et al, 2006]. Articaine infiltration has also been shown to improve the analgesia success in the maxillary lateral incisor area compared to lidocaine in adults [Evans et al., 2008]. This may be useful in the treatment of traumatic injuries in children and may avoid the need for palatal injections.

Many groups of patients may benefit from being able to avoid IANB for dental treatment, including children with special health care needs. Articaine buccal infiltration is currently being used as an alternative to IANB in patients with hereditary coagulation disorders to decrease need for factor replacement during the provision of restorative dental care. This is very cost-effective and allows some patients to receive treatment in primary care setting.

Conclusion

Articaine is a safe and effective local analgesia which offers many advantages when providing dental analgesia in children. Most noteworthy is the potential that IANB can be replaced by infiltration technique. Soft tissue analgesia may be prolonged, but the risk of other adverse reactions is similar to other local analgesia agents. It is important that the dose of articaine be calculated for each child as smaller volumes of the more concentrated local analgesia solution are required than lidocaine. Practitioners should be aware of the effectiveness of articaine to diffuse through bone and soft tissue to give excellent depth of analgesia, while avoiding block and palatal analgesia for dental treatment in children.

References

Adewumi A, Hall M, Guelmann M, Riley J. The incidence of adverse reactions following 4% septocaine (articaine) in children. Pediatr Dent 2008; 30:424-428.

Brandt RG, Anderson PF, McDonald NJ, Sohn W, Peters MC. The pulpal analgesia efficacy of articaine versus lidocaine in dentistry: a meta-analysis. J Am Dent Assoc. 2011; 142:493-504.

Brickhouse TH, Unkel JH, Webb MD, Best AM, Hollowell RL. Articaine use in children among dental practitioners. Pediatric Dentistry 2008; 30:516-521.

Corbett IP, Kanaa MD, Whitworth JM, Meechan JG. Articaine infiltration for analgesia of mandibular first molars. J Endod 2008; 34:514-518.

Dudkiewicz A, Schwartz S, Laliberte R. Effectiveness of mandibular infiltration in children using the local anesthetic Ultracaine (articaine hydrochloride). J Can Dent Assoc 1987; 53:29-31.

Evans G, Nusstein J, Drum M, Reader A, Beck M. A prospective, randomized, double-blind comparison of articaine and lidocaine for maxillary infiltrations. J Endod 2008; 34:389-393..

Hass DA, Lennon D. A 21 year retrospective study of reports of paresthesia following local anesthetic administration. J Can Dent Assoc 1995; 61:319-330.

Hasse A, Reader A, Nusstein J, Beck M, Drum M. Comparing analgesia efficacy of articaine versus lidocaine as a supplemental buccal infiltration of the mandibular first molar after an inferior alveolar block. J Am Dent Assoc 2008; 139:1312.

Jakobs W, Ladwig B, Cichon P, Ortel P, Kirch W. Serum levels of articaine 2% and 4% in children. Anesth Prog 1995; 42:113-115.

Kanaa MD, Whitworth JM, Corbett IP, Meechan JG. Articaine and lidocaine mandibular buccal infiltration anesthesia: a prospective randomized double blind cross-over study. J Endod 2006; 32:296-298. Epub 2006 Feb 17.

Kanaa MD, Whitworth JM, Corbett IP, Meechan JG. Articaine buccal infiltration enhances the effectiveness of lidocaine inferior alveolar nerve block. Int Endod J 2009; 42:238-246.

Katyal V. The efficacy and safety of articaine versus lidocaine in dental treatments: a meta-analysis. J Dent 2010; 38:307-317.

Malamed SF. Handbook of local analgesia 4th ed. St Louis Mo. DV Mosby 1997.

Malamed SF, Gagnon S, Leblanc D. Efficacy of Articaine: a new amide local analgesia. J Am Dent Assoc 2000a; 131:635-642.

Malamed SF, Gagnon S, Leblanc D. A comparison between articaine HCL and lidocaine HCL in pediatric dental patients. Pediatr Dent 2000b; 22:307-311.

Malamed SF, Gagnon S, Leblanc D. Articaine hydrochloride: a study of the safety of a new amide local anesthetic. J Am Dent Assoc 2001; 132:177-185.

Meecham JG. Local analgesia, risks and controversies. Dental Update 2009;36:278-283

Mikesell P, Nusstein J, Reader A, Beck M, Weaver J. A comparison of articaine and lidocaine for inferior alveolar nerve blocks. J Endod 2005; 31:265-270.

Odabas ME, Cinar C, Deveci C, Alagam A. Comparison of the Anesthetic Efficacy of Articaine and Mepivacaine in Pediatric Patients: A Randomized, Double-blind Study. Pediatr Dent 2012; 34:42-45.

Oertel R, Rahn R, Kirch W. Clinical pharmacokinetics of articaine. Clin Pharmacokinet. 1997; 33:417-425.

Oertel R, Ebert U, Rahn R, Kirch W. The effect of age on pharmacokinetics of the local analgesia drug articaine. Reg Anesth Pain Med 1999; 24:524-528.

Pogrel MA. Permanent nerve damage from inferior alveolar nerve blocks--an update to include articaine. J Calif Dent Assoc 2007; 35:271-273.

Poorni S, Veniashok B, Senthilkumar AD, Indira R, Ramachandran S. Anesthetic efficacy of four percent articaine for pulpal anesthesia by using inferior alveolar nerve block and buccal infiltration techniques in patients with irreversible pulpitis: a prospective randomized double-blind clinical trial. J Endod 2011; 37:1603-1607.

Ram D, Amir E. Comparison of articaine 4% and lidocaine 2% in paediatric dental patients. Int J Paediatr Dent 2006; 16:252-256.

Robertson D, Nusstein J, Reader A, Beck M, McCartney M. The analgesia efficacy of articaine in buccal infiltration of mandibular posterior teeth. J Am Dent Assoc 2007; 138:1104-1112.

Uckan S, Danangac E, Araz K. Is permanent maxillary tooth removal without palatal injection possible? Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 102:733-735.

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R. Leith *, K. Lynch **, A.C. O'Connell *

* Dublin Dental University Hospital, Trinity College Dublin.

** Mayberry Dental Care, Kilnamanagh, Dublin, Ireland

Postal address: R. Leith, Dept of Public and Child Dental Health, Dublin Dental University Hospital, Trinity College Dublin, Lincoln Place, Dublin 2, Ireland.

Email: rona.leith@dental.tcd.ie
Table 1. Pharmacological data for Articaine and Lidocaine
[Malamed, 1997; Malamed et al., 2000a; Malamed et al., 2001; Meecham,
2009]

                       Duration of pulpal   Duration of soft
                           analgesia        tissue analgesia
                           (minutes)            (hours)

Articaine 4%                 66 *                 3-5
1:100,000 adrenaline       [75.sup.+]

Articaine 4%                 56 *                 3-5
1:200,000 adrenaline       [45.sup.+]

Lidocaine 2%                   45                 3-5
1:80,000 adrenaline

                         mg dosage per LA      Maximum dosage
                             cartridge            (mg / kg)

Articaine 4%              88 in 2.2 ml *              7
1:100,000 adrenaline   68 in 1.7 [ml.sup.+]

Articaine 4%              88 in 2.2 ml *              7
1:200,000 adrenaline   68 in 1.7 [ml.sup.+]

Lidocaine 2%               44 in 2.2 mg            4.4 -7
1:80,000 adrenaline        34 in 1.7 ml

                         Maximum number
                       of 2.2ml cartridges
                        for a 20 kg child

Articaine 4%                   1.6
1:100,000 adrenaline

Articaine 4%                   1.6
1:200,000 adrenaline

Lidocaine 2%                  2- 3.2
1:80,000 adrenaline

* Septodont +3M

Table 2. Studies investigating the efficacy and safety
of articaine in children

Study                     Number of subjects   Age (years)

Dudkiewicz et al., 1987   50                   4-10

Wright et al., 1989       211                  <4

Malamed et al., 2000a     1325                 4-80

Malamed et al., 2000b     50                   4-13

Malamed et al., 2001      1325                 4-80

Mikesell et al., 2005     57                   4-80

Ram et al., 2006          62                   5-13

Adewumi et al., 2008      204                  2-14

Katyal, 2010              Meta-analysis        All ages
                          9 trials

Brandt et al., 2011       Meta-analysis        All ages
                          13 studies

Yilmaz et al., 2011       162                  6-8

Odabas et al., 2012       50                   7-13

Study                     Local anaesthetic used

Dudkiewicz et al., 1987   Articaine 4% 1:100000
                          vs. 1:200000 adrenaline

Wright et al., 1989       Articaine 4% 1:100000
                          vs. 1:200000 adrenaline

Malamed et al., 2000a     Articaine 4% 1:100000 vs.
                          Lidocaine 2% 1:100000 adrenaline

Malamed et al., 2000b     Articaine 4% 1:100000 vs.
                          Lidocaine 2% 1:100000 adrenaline

Malamed et al., 2001      Articaine 4% 1:100000 vs.
                          Lidocaine 2% 1:100000 adrenaline

Mikesell et al., 2005     IANB using Articaine 4% 1:100000
                          vs. Lidocaine 2% 1:100000

Ram et al., 2006          Articaine 4% 1:200000
                          infiltration vs. Lidocaine
                          2% 1:100000 adrenaline

Adewumi et al., 2008      Articaine 4% 1:100000
                          adrenaline infiltration

Katyal, 2010              Articaine 4% 1:100000 vs.
                          Lidocaine 2% 1:100000 adrenaline

Brandt et al., 2011       Articaine 4% vs.Lidocaine 2%

Yilmaz et al., 2011       Articaine 4% 1:100000 vs.
                          Prilocaine 3% with felypressin
                          infiltration or IANB for
                          primary molar pulpotomy

Odabas et al., 2012       Articaine 4% 1:200000
                          vs. mepivacaine 3%

Study                     Outcome

Dudkiewicz et al., 1987   Anaesthesia successful in
                          all cases No adverse
                          effects reported

Wright et al., 1989       No adverse effects noted
                          (retrospective analysis)

Malamed et al., 2000a     Pain control Efficacy:
                          No significant difference

Malamed et al., 2000b     Efficacy: Pain control
                          during simple & complex
                          procedures No significant
                          difference in pain relief
                          Safety; No serious adverse
                          events

Malamed et al., 2001      Safety: Adverse reactions
                          similar: Articaine 22%
                          vs Lidocaine 20%.

Mikesell et al., 2005     Articaine pulpal
                          anaesthesia: 4-54%
                          Lidocaine pulpal
                          anaesthesia: 2-48%
                          No significant difference

Ram et al., 2006          Efficacy similar Longer
                          soft tissue numbness with
                          articaine Few adverse
                          events with either agent

Adewumi et al., 2008      Prolonged numbness is most
                          frequent adverse event:
                          Occurs mostly in patients
                          <7yrs Prolonged numbness
                          may cause anxiety

Katyal, 2010              Articaine more effective
                          than lidocaine for
                          anaesthetising lower
                          FPM Similar adverse
                          effects profile

Brandt et al., 2011       Articaine provides a
                          higher rate of anaesthetic
                          success Stronger evidence
                          for articaine's superiority
                          with infiltration
                          anesthesia than with
                          mandibular block anaesthesia

Yilmaz et al., 2011       Similar intensity of pain
                          during administration of LA
                          Pain related behaviour score
                          for prilocaine 1.5 times
                          higher than articaine when
                          removing coronal pulp
                          Similar adverse events

Odabas et al., 2012       No difference in anaesthetic
                          efficacy Longer soft tissue
                          numbness with articaine
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Author:Leith, R.; Lynch, K.; O'Connell, A.C.
Publication:European Archives of Paediatric Dentistry
Article Type:Report
Geographic Code:4EUIR
Date:Dec 1, 2012
Words:3422
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