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The efficacy of an elevated concentration of lidocaine HCl in impacted lower third molar surgery

Background There have been few studies on the effect of an elevated concentration of lidocaine hydrochloride in the surgical removal of an impacted lower third molar. This study aimed to examine the efficacy of 4% lidocaine along with 1:100,000 epinephrine compared to 2% lidocaine along with 1:100,000 epinephrine as inferior alveolar nerve block for the removal of an impacted lower third molar. Methods This single-blind study involved 31 healthy patients (mean age: 23 y; range: 19-33 y) with symmetrically impacted lower third molars as observed on panoramic radiographs. Volunteers required 2 surgical interventions by the same surgeon with a 3-week washout period. The volunteers were assigned either 4% lidocaine with 1:100,000 epinephrine or 2% lidocaine with 1:100,000 epinephrine as local anesthetic during each operation. Results We recorded the time of administration, need for additional anesthetic administration, total volume of anesthetic used. We found that the patient's preference for either of the 2 types of local anesthetic were significantly different (P < 0.05). However, the extent of pulpal anesthesia, surgical duration, and duration of soft tissue anesthesia were not significantly different. Conclusions Our study suggested that inferior alveolar nerve block using 4% lidocaine HCl with 1:100,000 epinephrine as a local anesthetic was clinically more effective than that using 2% lidocaine HCl with 1:100,000 epinephrine; the surgical duration was not affected, and no clinically adverse effects were encountered.


INTRODUCTION
An impacted lower third molar is a common abnormality observed in the eruption pattern of human teeth, which requires surgical removal to prevent further complications and to reduce the susceptibility to disease, including bone pathology [1]. Such surgery requires an effective local anesthetic to achieve sufficient nerve block. Inferior alveolar nerve block (IANB) does not always result in successful pulpal anesthesia during the operation, even when the correct injection technique is followed [2,3]. Researchers have manipulated a range of variables to improve the effectiveness of the local anesthetic used in IANB, such as increasing its volume, modifying its concentration, adjusting its pH, or adding a buffering agent to the local anesthetic cartridge [3][4][5][6][7][8][9].
Besides 2% lidocaine with epinephrine, which is readily available commercially, 3% lidocaine with norepinephrine has become available in dental cartridge form [11].
However, very few studies report the effect of increasing lidocaine HCl concentration for surgical removal of impacted lower third molars. Thus, the purpose of this study was to examine the efficacy of 4% and 2% lido-

Inclusion criteria
Exclusion criteria • Symmetrically impacted third molars, requiring surgical removal • Presence of at least 1 healthy lower first or second molar on both sides (i.e., without caries or restoration) • Patient consent • Healthy volunteers, aged between 18 and 45 y • Non-smoker and non-alcoholic • Able to understand and carry out the instructions given by the investigators • Systolic blood pressure (> 140 mmHg, < 90 mmHg) • Diastolic blood pressure (> 90 mmHg, < 60 mmHg) • Heart rate (> 100 bpm, < 60 bpm) • Pregnancy or current lactation • Allergic to local anesthetics • Presence of facial deformities • Swelling and/or infection associated with the third molar site • Use of medication 5 days prior to surgery (analgesics, antidepressants) • Inability to follow the instructions or uncooperative during the study (1 mg/ml) was withdrawn from a 1-ml ampule into the lidocaine ampule.
The following formula was used to calculate the volume of the active ingredient: where C(i) = initial concentration , V(i) = initial volume,

RESULTS
The control group had a pH = 3.96, which was lower than that of the test group (pH = 5.79), after mixing of 4% lidocaine (pH = 5.83) with epinephrine (pH = 3). The type of impaction was accessed using a panoramic      during the administration of the drug into the soft tissue (Table 3), the 4% lidocaine group experienced more pain (20.77 ± 23.3 mm) than the 2% group (16.51 ± 14.21 mm), but the difference was not statistically significant.
During tooth-sectioning, however, the difference between the 2 types of anesthetic solutions was nearly significant (P = 0.052; Table 3 and 4). There was no significant difference between the 2 types of local anesthetics in terms of intensity of intra-operative pain. Table 4 shows the degree of intra-operative pain, from the absence of pain to severe pain, based on the VAS value as rated by the volunteers.
In this study, the EPT device was used to confirm pulpal anesthesia. Based on the status of healthy teeth, 62 canine, 58 first molars, and 4 second molars were tested. The results showed no significant differences between the solutions in terms of baseline values of pulpal anesthesia.
The distribution of the volunteers according to the occurrence of pulpal sensibility after 10 min was not signi-ficantly different between the groups (Fig. 1) Postoperatively, there were no signs of nerve dysfunction, paresthesia, or infection reported or assessed. Only a few volunteers reported a longer-acting anesthesia in the 4% lidocaine group, as shown in Table 2, but these values were not significantly different.

DISCUSSION
Volunteers with bilaterally symmetrical impaction provide us with the opportunity to conduct a blind split-mouth clinical study; in this way, the individual bias based on the difference in the degree of discomfort and the intensity of the pain response can be reduced. Some previous studies have addressed the effects of anesthetic solutions in third molar surgery without a split-mouth design, which confounds the comparison of the results [18]. We found that onset of anesthesia in the 4% lidocaine group was significantly faster, both subjectively and objectively, than in the 2% group. Our results were similar to those of a study by Chaney et al. [2]. The onset of local anesthesia can be influenced by the pH of the solution. We found that the test solution had a higher pH than the standard solution (5.79 vs. 3.96). A literature review indicated that on the injection side, the local anesthetic is converted to a quaternary salt (BH + ) and a tertiary base (B), which is one of the core factors that enhances the onset of anesthesia, via the pKa and the pH of physiological tissue [19,20]. It has been suggested that a rapid onset is promoted by a high pH [3,21].
Recently, Whitcomb et al. [3] found that adjustment of the pH of the lidocaine to 7.5 did not have any negative effects. Acidic solutions have been reported to produce a burning sensation in the tissue during drug administration [20]; however, in our research, the incidence of pain during drug administration was not significantly different between high and low pH solutions. These results corroborated those of other previous studies on pH-adjusted local anesthetics [2,3,9,22]. The rating of moderate (3%-16%) and severe pain (3.22%; Table 4) in our groups was lower than that reported in a study by Ridenour (2001), which rated moderate pain as 13%-23% and severe pain as 7% [22]. In terms of the VAS, the test and control groups rated pain as 20.77 ± 23.3 and 16.51 ± 14.21 mm, respectively, but these results were not significantly different.
The duration of soft tissue numbness is shown in  Tables 3 and 4 show the degree of intra-operative pain that the volunteers rated on the 0-100 mm VAS. In both groups, it was noted that the surgical removal of an impacted lower third molar was a painful operation, especially during the tooth-sectioning period, and required supplementary local anesthetic. The pain scale showed that the pain sensation remained between mild to moderate in both groups, but that the 4% lidocaine group experienced less intra-operative pain, although the difference was not significant. We also found that patients significantly preferred 4% lidocaine to 2% for surgical removal of impacted lower third molars (P = 0.004), because of reduced intra-operative pain. This result is in agreement with that of Rood's pilot study [6]. Another double-blind trial conducted by the same author showed that the success rate of IANB for the extraction of pulpally inflamed teeth was higher with 5% lidocaine (93%) with 1:80,000 epinephrine than with the standard 2% solution (22%).
Complications and adverse effects of anesthesia were other important variables that were evaluated in our research. Postoperatively, the volunteers were placed in a comfortable room for 1 h and were observed for any immediate side effects of the drug. None of the volunteers reported any adverse complications or paresthesia postoperatively or on the 7th-day follow-up visit. These findings were consistent with those of previous reviews and studies that have stated that lidocaine is the gold standard local anesthetic with low toxicity [20,24]. However, a high concentration of lidocaine has been reported to produce neurotoxicity in some in vitro studies [25].
Controversially, there have been no reports of neurotoxicity in humans [24]. Additionally, a study by Eldridge and Rood reported that the use of 50 mg/ml lidocaine with 1:80,000 epinephrine for routine dental treatment did not show any adverse clinical events, following which, this local anesthetic solution was used in a pediatric patient clinical trial, in which it was considered to be safe and in which no adverse reactions were observed [5,8]. EPT has become the standard research method to identify the extent of pulpal anesthesia after endodontic administration of local anesthetic [12][13][14][15][16]. In our study, there was no statistical difference in the percentage of teeth that achieved the maximum EPT output of 80 μA after 10 min post-injection with either solution (Fig. 1), although we found a higher percentage of maximum EPT output in the 4% lidocaine group than in the 2% lidocaine group. Interestingly, even when the EPT reached the maximum output of 80 μA, some patients still complained of pulpal sensitivity during tooth sectioning. It may have been because our procedure was more traumatizing to the pulp nerve bundle. Based on these findings, we suggest that a maximum output of 80 μA by the EPT device may not represent complete pulpal anesthesia in impacted lower third molar surgery during tooth sectioning.
Moreover, the total volume of local anesthetic used in each group was significantly higher in the 2% lidocaine group than in the 4% lidocaine group.
In our study, four cases in the 2% lidocaine group required repeated IANB, although those were subjective in nature and had reported complete lower lip numbness at the injection site. It is possible that failure of the injection or the effectiveness of the standard drug solution was inadequate to produce a sufficient objective onset of anesthesia. Moreover, there was a greater requirement for additional local anesthetic in the 2% lidocaine group; this need was significantly greater during the toothsectioning period, which may have been due to an insufficient volume of anesthetic to control pain during the operation.
Based on our results, we suggest that 4% lidocaine with 1:100,000 epinephrine can be used as a standard local anesthetic in dentistry, especially during the surgical removal of an impacted lower third molar. This concentration of lidocaine did not produce any adverse reaction in healthy adult patients in our study. Patients also significantly preferred it to 2% lidocaine for reducing operative pain.