Inferior alveolar nerve block (IANB) is the most common technique used to anesthetize

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1 Efficacy of Articaine versus Lidocaine in Block and Infiltration Anesthesia Administered in Teeth with Irreversible Pulpitis: A Prospective, Randomized, Double-blind Study Hengameh Ashraf, DDS, MS, Majeed Kazem, DDS, MS, Omid Dianat, DDS, MS, and Fatemeh Noghrehkar, DDS Abstract Introduction: Profound pulpal anesthesia in posterior mandibular teeth with irreversible pulpitis usually requires administering an inferior alveolar nerve block (IANB) plus other supplemental injections. The purpose of this prospective, randomized, double-blind study was to compare the anesthetic success rate of buccal infiltration injections of articaine and lidocaine when supplemented with an IANB. Methods: One hundred twenty-five emergency patients who had their first or second mandibular molar diagnosed with irreversible pulpitis participated in the study and received the IANB by using either 2% lidocaine with 1:100,000 epinephrine or 4% articaine with 1:100,000 epinephrine. One hundred two of the patients reported moderate-tosevere pain upon initiation of their endodontic treatment or through filing of their tooth canals and received supplemental buccal infiltration injections by using the same anesthetic that the IANB had been performed. After the block or the supplemental buccal infiltration injections, success was achieved with no or mild pain during instrumentation of the tooth canals. Results: The success rate after the administration of the infiltration injections after an incomplete IANB by using lidocaine was 29%, whereas by using articaine it was 71% (P <.001). No statistical differences were detected in the success rates between the 2 anesthetics after the block injections. Conclusions: Supplementing an incomplete articaine IANB with articaine infiltration raises the anesthetic success more effectively compared with lidocaine in mandibular molars with irreversible pulpitis. (J Endod 2013;39:6 10) From the Department of Endodontics, Faculty of Dentistry, Shahid Beheshti Medical University, Tehran, Iran. Supported by the research funding of Shahid Beheshti Medical University. This article was adapted from a thesis submitted by Dr Fatemeh Noghrehkar with the supervision of Dr Hengameh Ashraf. Address requests for reprints to Dr Fatemeh Noghrehkar, Endodontics Department, Faculty of Dentistry, Shahid Beheshti Medical University, Tehran , Iran. address: fnoghrehkar@gmail.com /$ - see front matter Copyright ª 2013 American Association of Endodontists. Key Words Articaine, infiltration, irreversible pulpitis, lidocaine Inferior alveolar nerve block (IANB) is the most common technique used to anesthetize posterior mandibular teeth during endodontic procedures (1 4). However, it fails to perform effectively 10% 81% of the time (1 6). Supplemental techniques such as the intraosseous, intraligamentary, and infiltration injections have been studied to raise anesthetic success rates (6 9). The intraosseous injection seems to raise the success rate to a reliable extent as shown in some previous studies (10). It is not a preferable technique because it requires special equipment, drilling of the cortical bone, and preparing a site for administration of the anesthetic solution (11). The intraligamentary injections have a short duration of action and may increase postoperative pain (12). The intraosseous and intraligamentary techniques are effective in raising anesthesia levels in difficult anesthetic situations; however, it would be beneficial if similar results could be achieved by simpler options such as the infiltration technique. This technique has been studied extensively in asymptomatic teeth (13 19). Some of these studies performed a comparison between lidocaine and articaine (13 16). The results of some revealed no significant differences between the 2 anesthetics (13, 14), whereas the findings of others suggested that articaine was superior to lidocaine in raising pulpal anesthesia in mandibular teeth (15, 16). In a study by Kanna et al (20), lidocaine and articaine were compared in maxillary teeth with irreversible pulpitis. The results of their study showed no significant differences between these anesthetics. In a study by McEntire et al (21), the anesthetic efficacy of 4% articaine with 1:200,000 epinephrine was shown to be comparable to 4% articaine with 1:100,000 epinephrine in a primary mandibular buccal infiltration of asymptomatic mandibular first molars. In a study by Poorni et al (22) on mandibular molars with irreversible pulpitis, the efficacy of an IANB with articaine or lidocaine showed similar success rates compared with a buccal infiltration with articaine that had not been supplemented with an IANB. This may bring up the point that the infiltration technique could be a reliable choice of anesthesia. Aggarwal and colleagues (23) performed a study on mandibular molars with irreversible pulpitis. Their findings showed that lidocaine IANB along with supplementary infiltration of articaine or articaine plus ketorolac tromethamine increased the anesthesia success rates to 54% and 62%, respectively. In a study by Matthews et al (9), supplemental articaine infiltration injections were administered after failure of lidocaine IANB in posterior mandibular teeth with irreversible pulpitis. They found that the articaine infiltration injection was successful 58% of the time. Aggarwal et al (6) compared lidocaine and articaine infiltration injections that were applied on both buccal and lingual sides of posterior mandibular teeth with irreversible pulpitis after lidocaine IANB. They found the success rates of lidocaine and articaine to be 47% and 67%, respectively. Even though these studies investigated mandibular teeth with irreversible pulpitis, they had performed the IAN blocks by using lidocaine, and the obtained results would not predict pulpal anesthesia in all patients 6 Ashraf et al. JOE Volume 39, Number 1, January 2013

2 requiring endodontic treatments. Because the infiltration injections with articaine enhanced the success rate of pulpal anesthesia, we thought it was possible to raise the success rate further if the block injections were also administered by articaine. We therefore compared the degree of anesthesia achieved by applying either 2% lidocaine with 1:100,000 epinephrine or 4% articaine with 1:100,000 epinephrine if both the IANB and infiltration injections were performed by using the same anesthetic solution in the first and second mandibular molars with irreversible pulpitis. Materials and Methods One hundred twenty-five emergency patients experiencing pain in their first or second mandibular molar who were attending Shahid Beheshti University s dependent dental clinic participated in this study. Patients were given a questionnaire first, and those who were younger than 20 years, pregnant women, patients with systemic disease, and those with clinically observed lesions or swellings at the injection site were excluded from the study. The Ethics Committee in Shahid Beheshti Medical University approved the protocol of the study. Written informed consent was obtained from each participant. All patients were experiencing active pain in their first or second mandibular molar and had not taken any pain killers on the day of treatment. Prolonged response to cold testing by using an ice stick, vital pulp tissue during access opening, and the absence of periapical radiolucencies on periapical radiographs (except for periodontal ligament widening) confirmed the presence of irreversible pulpitis in the teeth. The Heft-Parker visual analogue scale (HP-VAS) was used to rate the pain experienced by patients throughout the treatment. HP-VAS was a 170-mm line divided into different categories of pain. Different marks on the line showed a description of a certain pain level. Absence of pain corresponded to 0 mm. Mild pain with the descriptors of faint, weak, and mild pain corresponded to greater than 0 mm up to 54 mm, moderate pain corresponded to greater than 54 mm up to 114 mm, and severe pain with the descriptors of strong, intense, and maximum possible amount of pain corresponded to greater than 114 mm up to 170 mm. Patients were asked to rate their pain before initiation of their treatment, after the block injections, and after receiving the infiltration injections for those who required them. The study was given a parallel design with the allocation ratio of N articaine/n lidocaine for each primary and final outcome. Initially, the patients were divided into 2 groups of men and women, who were then classified randomly into 2 subgroups of lidocaine or articaine by using random allocation software. One blinded nurse enrolled all participants and assigned them to intervention. There were equal numbers of lidocaine and articaine cartridges available that had been covered and given a code. Another nurse in the department was aware of the codes and gave out the cartridges randomly and in equal numbers according to the subgroups of lidocaine or articaine. There was 1 code for each of the 2 cartridges packed together because Assessed for eligibility (n= 156) Not meeting inclusion criteria (n= 22 ) Declined to participate (n= 7 ) Other reasons (n= 2) Randomized (n= 125) Received IANB (n= 125) Did not receive supplemental infiltration injections due to successful IANB or absence of lip numbness after IANB (n= 23) Received allocated intervention of lidocaine infiltration (n= 51) Received allocated intervention of articaine infiltration (n= 51) Analysed (n= 51) Analysed (n= 51) Figure 1. Flow diagram demonstrating patient assignment to different groups. JOE Volume 39, Number 1, January 2013 Efficacy of Articaine versus Lidocaine in Block and Infiltration Anesthesia 7

3 the block and infiltration injections were supposed to be administered by using the same anesthetic. All patients received 1.5 ml of either anesthetic solution for the block injection, and 0.3 ml (almost one-eighth of a cartridge s content) was used for the long buccal injections. The infiltration injections were performed by using 1.8 ml of the same anesthetic for those required. All the injections were given by the same clinician. All patients received the standard IANB and long buccal injections by use of 2% lidocaine with 1:100,000 epinephrine (Persocaine- E; Darou Pakhsh Pharmaceutical Manufacturing Co, Tehran, Iran) or 4% articaine with 1:100,000 epinephrine (Septocaine; Septodont, Lancaster, PA) that were based on the code of their cartridges. After 15 minutes, they were asked whether they were having lip numbness. Patients who did not report lip numbness were excluded from the study, and their cartridges were replaced. Those who reported lip numbness were studied for data analyses. The procedure included isolating the teeth with a rubber dam, preparing the access cavity, and performing the initial filing of the canals. Patients were instructed to rate any discomfort on the HP-VAS scale through the different steps of the treatment. If according to the HP-VAS scale the patient experienced no pain or mild pain after the IANB, the block was considered successful, and endodontic treatment was carried out without applying the supplemental infiltration injections. For those who had moderate-to-severe pain on the basis of the values of the HP-VAS scale, the rubber dam was removed, and the infiltration injection was administered with the same anesthetic solution that the block injection had been performed. For the infiltration injections 27-gauge short needles (Septoject; Septodont) were used, and the needle was advanced until the estimated apical root position of the teeth. The cartridge content was deposited at a rate of 1 ml/min. After 5 minutes the endodontic treatment continued, and success of the block or supplemental infiltrations was defined as the ability to continue the procedure of preparing the access cavity or initial filing of the canals with no or mild discomfort (Fig. 1). Statistical Analyses The mean continuous variables between the 2 intervention groups were compared by using the independent sample t test. The number of patients in each group was determined by using PS vs (power and sample size calculation software; Department of Biostatistics, Vanderbilt University, Nashville, TN). For the power of our study to be more than 80% (20% false negative), detecting 15% difference in the success rates of the groups of lidocaine or articaine infiltrations, we allocated 50 patients in each group. We assumed a dropout of 25 patients because of absence of lip numbness after the IANB or other reasons of missing data. The total number of our study population was therefore calculated around 125 subjects. Significant level was considered as P <.05. Considering the binary outcome, we applied logistic regression by using SPSS vs (SPSS Inc, Chicago, IL). Results One hundred twenty-five adult patients aged years received the IANB and participated in the study. The IANB was successful in 14% of the patients (17/125). Six patients did not experience lip numbness after the IANB. Twenty-three patients did not receive the supplemental infiltration injections. There were no significant differences in the block injections between the 2 anesthetic solutions. One hundred two of the patients, including 47 men (47/102) and 55 women (55/102), received the supplemental infiltration injections. The total number of successful infiltration injections was 58 of 102 (57%). The anesthetic success was 71% by use of articaine and 29% by use of lidocaine (P <.001). Articaine had 4 times greater chance of being effective in the infiltration injections according to our age- and sex-adjusted logistic regression analysis (odds ratio = 4.343; 95% confidence interval, ; P <.002). The second molars showed higher success rates than the first molars (28% versus 72%, P <.01). There were no significant differences detected between men and women regarding the success rates of the 2 anesthetics (50% versus 50%). Percentage and number of successful injections according to the different anesthetics, teeth, and sex groups are shown in Table 1. Discussion The results of our study indicated that the anesthetic success of articaine infiltrations after incomplete anesthesia achieved by articaine IANB was 71% and that of lidocaine infiltrations after incomplete anesthesia achieved by lidocaine IANB was 29%. This is higher than the values reported by Matthews et al (9) and Aggrawal et al (6) of 58% and 67%, respectively, for articaine infiltration anesthesia in posterior mandibular teeth with irreversible pulpitis. However, they had performed all the IANBs by using 2% lidocaine with 1:100,000 epinephrine, whereas half of our block injections were administered by using articaine, and we were able to compare the 2 anesthetics in both the block and infiltration injections. The higher success rate achieved in our study could therefore be due to performing both the block and infiltration injections with articaine. The difference of 4% between our results and the findings of Aggarwal et al (6) is not significant. However, they had administered the infiltration injections on both the buccal and lingual sides of the mandibular teeth, but we omitted the lingual side to avoid the possible threats to lingual nerve, and yet we found nearly similar results. We also performed logistic regression analysis on our data, which takes the role of other variables such as age, sex, and the type of tooth into account and provides us with a more realistic result. These findings indicated that regardless of the patient s age, sex, and the type of tooth under treatment, the chance of articaine for a successful infiltration injection will be 4 times greater than that of lidocaine. TABLE 1. Percentage and Number of Successful Injections on the Basis of the Different Anesthetics, Teeth, and Sex Groups Articaine Lidocaine P value* Age ( mean standard deviation) (y) 37.9 (10.0) 32.5 (8.7) <.01 Men 24/47 (51%) 23/47 (49%) NS Women 27/55 (49%) 28/55 (51%) NS First molar 17/42 (40%) 25/42 (60%).05 Second molar 34/60 (57%) 26/60 (43%).05 Successful block injections 8/17 (47%) 9/17 (53%) NS Successful infiltration anesthesia 41/58 (71%) 17/58 (29%) <.001 NS, not significant. *Chi-square test. 8 Ashraf et al. JOE Volume 39, Number 1, January 2013

4 In a study by Kanna et al (24) on mandibular teeth with irreversible pulpitis, buccal infiltration with articaine after lidocaine IANB was successful 84% of the time. The higher success rate in their study could be due to a higher volume of the anesthetic solution used (2.0 ml) for the infiltration injections. Martin et al (25) compared the anesthetic efficacy of the buccal infiltration of 1.8 ml with 3.6 ml 4% articaine in asymptomatic mandibular first molars. The 3.6-mL volume of the anesthetic showed a statistically higher success rate of 70% compared with 50% success rate achieved by 1.8 ml of the anesthetic solution. After administration of the IANBs, endodontic treatment was initiated, and the infiltration injections were not performed until the pain ratings on the HP-VAS proved the need for supplemental anesthesia. Thus, we were able to determine the efficacy of the block injections by using either lidocaine or articaine in teeth with irreversible pulpitis, and patients did not receive supplemental injections when there was no indication for their use. It should be noted that the presence of lip numbness does not always ensure profound pulpal anesthesia by IANB (5, 16, 26). The IANB only performed effectively in 17 of 125 patients, suggesting that supplemental injections would be required in most of the cases of posterior mandibular teeth with irreversible pulpitis. The degree of pulpal anesthesia was measured by using HP-VAS, and further tests with an electric pulp tester (EPT) were eliminated in our study. This was based on the findings of Nusstein et al (27) on teeth with irreversible pulpitis in which EPT was used for measuring the pain level. Their results demonstrated that 42% of patients with negative response to EPT after receiving anesthesia still reported pain during treatment and needed supplemental injections. We did not find significant statistical differences between articaine and lidocaine in the IANBs. Similar findings have been reported in other studies (5, 28, 29). It has been shown that buccal infiltration alone would induce anesthesia for a short period of time (16). A successful IANB would therefore be useful in both raising the anesthetic success and prolonging the duration of action. We divided men and women into 2 different groups and carried out the study independently for each group. We thought there may be some differences between them such as different reactions to pain. There were no significant differences detected between men and women regarding the success rates of the 2 anesthetics (50% versus 50%). We found the infiltration injections to act more effectively in the second mandibular molars. The number of injections performed by using lidocaine and articaine was equal, but the teeth were randomly selected to receive either of the anesthetics by random allocation software. The second molars happened to receive the articaine infiltration injections more frequently. This may have been the reason for their higher success rate. It would be beneficial if further studies measured the anesthetic efficacy of articaine on second molars with irreversible pulpitis, because the thicker bone present at the site of these teeth would be expected to lower their success rate. The results of the studies of Oliveira et al (30) and Costa et al (31) suggested that the duration of pulpal anesthesia also lasts longer with articaine than with lidocaine. We should point out that we waited 15 minutes after the IANB and 5 minutes after the infiltration injections, which was based on the time suggested by previous studies for these injections to take full effect (3, 16). The impacts of the anesthetics used were therefore maximized in our study. Some studies have shown that articaine use may lead to a higher incidence of paresthesia (32, 33). None of the subjects in our study revealed any signs of paresthesia. In the study of Haas and Lennon (32), it was shown that paresthesia associated with articaine or prilocaine is rare, with an incidence of 1:785,000 injections. Malamed et al (34) reported equal incidence of paresthesia for articaine and lidocaine in their study of 1325 patients. It should be noted that the paresthesias resolved in all the involved patients. To the best of our knowledge, administration of both the block and infiltration injections with articaine in mandibular teeth with irreversible pulpitis was done in our study for the first time. It would be worthwhile to perform further studies on teeth with irreversible pulpitis and the efficacy of articaine in these teeth. Our higher chance of success rate of 4 times with articaine than with lidocaine according to our logistic regression analysis would provide dentists and patients with better anesthesia choices if future studies confirm such findings. Conclusion Applying supplemental injections after the IANB in posterior mandibular teeth with irreversible pulpitis would be necessary for most patients. Articaine seems to raise anesthetic success more effectively compared with lidocaine after an incomplete IANB is supplemented with an infiltration injection by using the same anesthetic for both injections in teeth with irreversible pulpitis. Achieving profound pulpal anesthesia in all patients remains a future goal requiring further investigation. Acknowledgments The authors deny any conflicts of interest related to this study. References 1. Dagher BF, Yared GM, Machtou P. The anesthetic efficacy of volumes of lidocaine in inferior alveolar nerve blocks. J Endod 1997;23: Goldberg S, Reader A, Drum M, et al. Comparison of the anesthetic efficacy of the conventional inferior alveolar, Gow-Gates, and Vazirani-Akinosi techniques. J Endod 2008;34: Vreeland DL, Reader A, Beck M, et al. An evaluation of volumes and concentrations of lidocaine in human inferior alveolar nerve block. J Endod 1989;15: Cohen HP, Cha BY, Spangberg LS. Endodontic anesthesia in mandibular molars: a clinical study. J Endod 1993;19: Mikesell P, Nusstein J, Reader A, et al. A comparison of articaine and lidocaine for inferior alveolar nerve blocks. J Endod 2005;31: Aggarwal V, Jain A, Kabi D. Anesthetic efficacy of supplemental buccal and lingual infiltrations of articaine and lidocaine after an inferior alveolar nerve block in patients with irreversible pulpitis. J Endod 2009;35: Childers M, Reader A, Nist R, et al. Anesthetic efficacy of the periodontal ligament injection after an inferior alveolar nerve block. J Endod 1996;22: Nusstein J, Reader A, Nist R, et al. Anesthetic efficacy of the supplemental intraosseous injection of 2% lidocaine with 1:100,000 epinephrine in irreversible pulpitis. J Endod 1998;24: Matthews R, Drum M, Reader A, et al. Articaine for supplemental buccal mandibular infiltration anesthesia in patients with irreversible pulpitis when the inferior alveolar nerve block fails. J Endod 2009;35: Bigby J, Reader A, Nusstein J, et al. Articaine for supplemental intraosseous anesthesia in patients with irreversible pulpitis. J Endod 2006;32: Hargreaves KM, Keiser K. Local anesthetic failure in endodontics: mechanisms and management. Endod Topics 2002;1: McLean ME, Wayman BE, Mayhew RB. Duration of anesthesia using the periodontal ligament injection: a comparison of bupivacaine to lidocaine. Anesth Pain Control Dent 1992;1: Haas DA, Harper DG, Saso MA, et al. Lack of differential effect by Ultracaine (articaine) and Citanest (prilocaine) in infiltration anaesthesia. J Can Dent Assoc 1991;57: Haas DA, Harper DG, Saso MA, et al. Comparison of articaine and prilocaine anesthesia by infiltration in maxillary and mandibular arches. Anesth Prog 1990;37: Kanaa MD, Whitworth JM, Corbett IP, et al. Articaine and lidocaine mandibular buccal infiltration anesthesia: a prospective randomized double-blind cross-over study. J Endod 2006;32: Robertson D, Nusstein J, Reader A, et al. The anesthetic efficacy of articaine in buccal infiltration of mandibular posterior teeth. J Am Dent Assoc 2007;138: Corbett IP, Kanaa MD, Whitworth JM, et al. Articaine infiltration for anesthesia of mandibular first molars. J Endod 2008;34: JOE Volume 39, Number 1, January 2013 Efficacy of Articaine versus Lidocaine in Block and Infiltration Anesthesia 9

5 18. Jung YIL, Kim JH, Kim SE, et al. An evaluation of buccal infiltrations and inferior alveolar nerve blocks in pulpal anesthesia for mandibular first molars. J Endod 2008;34: Meechan JG, Kanaa MD, Corbett IP, et al. Pulpal anaesthesia for mandibular permanent first molar teeth: a double-blind randomized cross-over trial comparing buccal and buccal plus lingual infiltration injections in volunteers. Int Endod J 2006;39: Kanaa MD, Whitworth JM, Meechan JG. A comparison of the efficacy of 4% articaine with 1:100,000 epinephrine and 2% lidocaine with 1:80,000 epinephrine in achieving pulpal anesthesia in maxillary teeth with irreversible pulpitis. J Endod 2012;38: McEntire M, Nusstein J, Drum M, et al. Anesthetic efficacy of 4% articaine with 1:100,000 epinephrine versus 4% articaine with 1:200,000 epinephrine as a primary buccal infiltration in the mandibular first molar. J Endod 2011;37: Poorni S, Veniashok B, Senthilkumar AD, et al. 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: Aggarwal V, Singla M, Rizvi A, et al. Comparative evaluation of local infiltration of articaine, articaine plus ketorolac, and dexamethasone on anesthetic efficacy of inferior alveolar nerve block with lidocaine in patients with irreversible pulpitis. J Endod 2011;37: Kanaa MD, Whitworth JM, Meechan JG. A prospective randomized trial of different supplementary local anesthetic techniques after failure of inferior alveolar nerve block in patients with irreversible pulpitis in mandibular teeth. J Endod 2012;38: Martin M, Nusstein J, Drum M, et al. Anesthetic efficacy of 1.8 ml versus 3.6 ml of 4% articaine with 1:100,000 epinephrine as a primary buccal infiltration of the mandibular first molar. J Endod 2011;37: Nusstein J, Reader A, Beck FM. Anesthetic efficacy of different volumes of lidocaine with epinephrine for inferior alveolar nerve blocks. Gen Dent 2002;50: Nusstein J, Reader A, Nist R, et al. Anesthetic efficacy of the supplemental intraosseous injection of 2% lidocaine with 100,000 epinephrine in irreversible pulpitis. J Endod 1998;24: Tortamano IP, Siviero M, Costa CG, et al. A comparison of the anesthetic efficacy of articaine and lidocaine in patients with irreversible pulpitis. J Endod 2009;35: Claffey E, Reader A, Nusstein J, et al. Anesthetic efficacy of articaine for inferior alveolar nerve blocks in patients with irreversible pulpitis. J Endod 2004;30: Oliveira PC, Volpato MC, Ramacciato JC, Ranali J. Articaine and lignocaine efficiency in infiltration anaesthesia: a pilot study. Br Dent J 2004;197: Costa CG, Tortamano IP, Rocha RG, et al. Onset and duration periods of articaine and lidocaine on maxillary infiltration. Quintessence Int 2005;36: Haas DA, Lennon D. A 21 year retrospective study of reports of paresthesia following local anesthetic administration. J Can Dent Assoc 1995;61:319 20, , Miller P, Lennon D. Incidence of local anesthetic-induced neuropathies in Ontario from J Dent Res 2000;79: 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: Ashraf et al. JOE Volume 39, Number 1, January 2013