Comparing the Efficacy of Twin Mix and Lidocaine for Inferior Alveolar Nerve Blocks in Patients With Symptomatic Irreversible Pulpitis

Abstract

This randomized, active-controlled, double-blind, prospective clinical trial evaluated the anesthetic efficacy of 2% lidocaine with 1:200,000 epinephrine versus an admixture of 2% lidocaine with 1:200,000 epinephrine and 1 mL of 4 mg dexamethasone (Twin mix) for inferior alveolar nerve blocks (IANBs) in patients with symptomatic irreversible pulpitis (SIP) of the mandibular molars. Seventy-eight patients with SIP of mandibular molars were randomly allocated to the 2 groups of 39 subjects. All patients were required to have profound lip numbness within 10 minutes of local anesthetic deposition. The efficacy of pulpal anesthesia was confirmed by absence of pain or mild pain (Heft-Parker visual analogue scale ≤54 mm) during access cavity preparation and placement of glide path files. The collected data were subjected to independent t test, chi-square test, and Fisher exact test using SPSS software version 20.0 at a significance level of 0.05. IANB success rates for the lidocaine group and the Twin mix group was 66% and 68% respectively, which was not a statistically significant difference (p > .05). This study demonstrated that the anesthetic efficacy of Twin mix was equivalent to 2% lidocaine for IANBs in teeth with SIP.

The inferior alveolar nerve block (IANB) is an injection technique regularly used to achieve pulpal anesthesia for mandibular teeth requiring endodontic treatment.¹ However, this technique has a failure rate of 30–80% in teeth with symptomatic irreversible pulpitis (SIP), and many patients experience pain during access cavity preparation and instrumentation.^1–3 Failure may be attributed to several factors, including anatomic variability leading to difficulty with needle placement, accessory innervation, psychological implications, and the effects of inflammation on local tissue pH, local blood flow, nociceptors, and central sensitization.² However, the exact mechanism for failure often remains elusive. Considerable research has been directed at improving the success rate of IANBs in patients with SIP. This has included utilizing different injection techniques, anesthetic solutions, and supplemental injections; premedication; and the addition of adjuncts to the local anesthetic solution.^4–6

Dexamethasone is a glucocorticosteroid used for suppressing the immune system and controlling inflammation. Numerous studies report that premedication and supplemental injections with dexamethasone improve the efficacy of lidocaine in cases with SIP.^4,7 A systematic review by Nogueira et al⁸ concluded that dexamethasone is effective in relieving pain in patients with SIP when administered as an oral tablet, intracanal medicament, or supraperiosteal injection.

As a single injection admixture, 1.8 mL of 2% lidocaine with 1:200,000 epinephrine and 1 mL of 4 mg dexamethasone (Twin mix) has been studied for its anesthetic efficacy in third molar surgeries. It shortens the anesthetic latency, prolongs the duration of anesthesia, and decreases postoperative discomfort in third molar surgeries.⁹ Previous studies have concluded that a combination of a local anesthetic and perineural dexamethasone prolongs sensory block duration without increased neural toxicity.¹⁰

However, no study has investigated the efficacy of Twin mix in patients with SIP. Therefore, the objective of this study was to compare the anesthetic efficacy of Twin mix versus 2% lidocaine with 1:200,000 epinephrine for IANBs in patients presenting with SIP in mandibular first or second molars. The null hypothesis for this study is that there is no difference between Twin mix and 2% lidocaine with 1:200,000 epinephrine for the success rate of IANB anesthesia in teeth with SIP. The primary expected outcome is more profound pulpal anesthesia in patients with SIP permitting painless endodontic therapy.

METHODOLOGY

This single-center, prospective, randomized, active-controlled, double-blind clinical trial was approved by the Institutional Ethical Committee of Army College of Dental Sciences (ACDS/IEC/01/Dec2016) and registered with Clinical Trials Registry, India, no. CTRI/2017/05/008544. The different steps of the study followed the CONSORT guidelines.

Patients reporting to the Department of Conservative Dentistry and Endodontics, Army College of Dental Sciences, who were diagnosed with SIP involving the mandibular molars as assessed by an independent operator were assessed for eligibility. Symptomatic irreversible pulpitis was characterized by spontaneous pain, lingering sensitivity to cold, and referred pain, with no pain or discomfort on percussion. Criteria for inclusion in the study were (a) age 18–50 years, (b) history of pain suggestive of SIP, (c) lingering response to cold test, (d) having 1 adjacent healthy tooth plus a healthy contralateral canine to serve as control, and (e) absence of periapical pathology in diagnostic radiograph. Exclusion criteria were (a) existence of acute infection and/or swelling, (b) systemic disorders, (c) pregnancy, (d) any medication that may alter pain perception like analgesics, sedatives, antianxiety drugs, or antidepressants, (e) contraindications for using dexamethasone, and (f) a history of allergy to local anesthesia.

An a priori power analysis using a two-tailed alpha of .05, a power of 80%, and an effect size of ±25% in local anesthetic success was performed with the Fleiss formula to calculate a sample size of 37 subjects per group. Of the 100 patients diagnosed with SIP, 78 fulfilled the eligibility criteria and were enrolled in the study (Figure). Written informed consent was obtained from all the participants.

The flow chart of sample size selection and subgroup division based on CONSORT.

Participants assessed their initial pain using a 170-mm Heft-Parker visual analogue scale (HP-VAS) as a preliminary step. The HP-VAS scale was subdivided into 4 descriptive scoring categories: no pain (0; 0 mm), mild pain (1; 1–54 mm), moderate pain (2; 55–113 mm), and severe pain (3; 114–170 mm). Only patients exhibiting moderate and severe initial pain (HP-VAS scores of 2 and 3) were included in this study. A prolonged response to cold test (Endo-frost; Coltene-Whaledent, Langenau, Germany) was pathognomonic of SIP. Patients were then randomly allocated into two groups of 39 using a web program (available at www.randomizer.org).

For both groups, 1.8 mL of 2% lidocaine with 1:200,000 epinephrine (Lox 2%; Neon Laboratories Ltd, Mumbai, India) was drawn into a sterile 5-mL Luer lock syringe fitted with a 26-gauge, 1½-inch (38-mm) needle (Unolok, Hindustan Syringes & Medical Devices, Ballabgarh, India) by a dental assistant. This was followed by drawing 1 mL of 4 mg dexamethasone (Decaden, Wockhardt Ltd, Mumbai, India) into the same syringe for the test (Twin mix) group and 1 mL of distilled water for the control (lidocaine) group. Both groups received equivalent total dosages of lidocaine (36 mg) and epinephrine (0.009 mg) per injection. The dental assistant prepared the solutions and coded the syringes numerically according to the active ingredients before delivery to operator 1, who administered all the injections. Both the operator and the patient were blinded to the contents of the anesthetic syringe.

With the patient placed in a reclined position and the patient's mouth fully open, the coronoid notch and the posterior border of the ramus were identified by the operator's thumb and index finger respectively, with the line between the finger and thumb determining the height of the injecting site. The injection site was the mucosal tissue overlaying the medial surface of the ramus, lateral to the pterygomandibular raphe. The syringe was positioned parallel to the mandibular occlusal plane and directed from the premolars of the opposite side. The needle was advanced slowly until bony contact was felt. The needle was then withdrawn slightly, aspiration was performed, and the test solution was deposited at a speed of ∼1 mL/min.

Operator 2 performed the preinjection and postinjection tests for pulpal response with an electric pulp tester (Gentle Pulse Analog Pulp Vitality Tester; Parkell, Edgewood, NY) for the indicated tooth and the contralateral canine. Electric pulp test (EPT) on the contralateral canine, which was not anesthetized, was used as a control to ensure that the equipment was working and to verify the patient's response. Ten minutes after injection, the patient was questioned about lip numbness and EPT was repeated. The criterion for successful pulpal anesthesia was 2 consecutive readings of 80 μA. If lip numbness or negative EPT was not achieved, a second injection of the same local anesthetic solution was given. After another 10 minutes the EPT was repeated and signs of lip anesthesia recorded. Only patients with no response to EPT continued to participate in the study. Patients who continued to respond to EPT were eliminated from the study.

Operator 1, who performed the injections, initiated endodontic access under rubber dam (Coltene-Whaledent, Langenau, Germany) isolation and subsequently placed a number 10 K-File (Dentsply Maillefer, Tulsa, OK) in the root canals to length as approximated from the preoperative radiograph. Pain and discomfort experienced by the patient during access or instrumentation was recorded using the HP-VAS scale.

The efficacy of anesthesia was recorded successful if patients reported no (score 0) or mild (score 1) pain during pulpal access and endodontic file placement. Subsequently, the routine root canal procedure was completed. If the patient experienced moderate (score 2) or severe (score 3) pain per the HP-VAS scale, the efficacy of anesthesia was deemed unsuccessful and recorded as a failure. Supplemental anesthesia was given as needed and the root canal procedure completed.

The results were tabulated and analyzed using SPSS 20.0 (SPSS Inc, Chicago, Ill). The results for Twin mix and lidocaine groups were calculated as mean ± SD. They were compared statistically for age and initial pain score using independent t test. Differences in gender, tooth type, and anesthetic success were analyzed using chi-square test and Fisher exact test. Comparisons at p < .05 were considered statistically significant.¹¹

RESULTS

The age, gender, and tooth type data for the 78 enrolled patients are listed in Table 1. There were no statistically significant differences (p > .05) between the 2 groups with respect to age, gender, and tooth type. The groups were considered homogenous and the results were compared.

Table 1. .

Age, Gender, and Tooth Type for Lidocaine and Twin Mix Groups

	Lidocaine	Twin Mix	p Value
Age, y	32 ± 9	29 ± 8	.15*
Gender			.88*
Male	15	15
Female	24	24
Tooth type			.84*
First molar	29	29
Second molar	10	10

^*p > .05.

All patients reported lip numbness after the initial IANB, with 25 patients in the lidocaine group and 29 patients in the Twin mix group not responding to EPT. The remaining patients received a second injection because of the EPT response. After the second injection for those patients, another 10 patients in the lidocaine group and 5 in the Twin mix group no longer responded to EPT. Pulpal anesthesia was considered successful in 89% (35/39) of the lidocaine group and 87% (34/39) of the Twin mix group as based on lip numbness and no response to EPT (Table 2). However, this difference between the 2 experimental groups was not statistically significant (p = 1).

Table 2. .

Results of Sequential Evaluation Tests and the Anesthetic Success Rate for Lidocaine and Twin Mix Groups (n = 78)*

	Lidocaine (n = 39)	Twin Mix (n = 39)	p Value
Patients with no response to EPT (first dose)	25	29
Patients requiring second dose of anesthetic	14	10
Patients with no response to EPT (second dose)	10	5
Patients with positive EPT after second dose	4	5
No. (%) of patients with no response to EPT reading	35 of 39 (89.74)	34 of 39 (87.17)	1.00
No. (%) of patients with anesthetic success	23 of 35 (66)	23 of 34 (68)	.625
No. (%) of patients with anesthetic failure	12 of 35 (34.28)	11 of 34 (32.35)

^*EPT indicates electric pulp test.

No pain/mild pain as reported by patient HP-VAS scores of 0 or 1 during access cavity preparation and initial instrumentation indicated successful anesthesia. Patients reporting moderate to severe pain scores of 2 or 3 during access cavity preparation were considered anesthetic failures. The success rates for the lidocaine and the Twin mix groups were 66% (23/35) and 68% (23/34), respectively (Table 2). There was no statistically significant difference (p = .625) in the success rate of anesthesia between the 2 groups. Of the original 78 patients, 4 from the lidocaine group and 5 from the Twin mix group continued to respond to EPT despite a second injection and were excluded from the study (Table 2). The primary outcome of the study, the IANB success rate, was 66% and 68% for the lidocaine and Twin mix groups respectively.

DISCUSSION

Conventional IANB is the most popular technique used for anesthetizing mandibular molars. However, its anesthetic efficacy for teeth with SIP is as low as 15–57%, leading to research focused on improving the efficacy of IANBs.^1–3 Previous studies have investigated adjuvants such as meperidine, diphenhydramine, hyaluronidase, and sodium bicarbonate without any significant improvement over standard lidocaine with epinephrine solutions.^12–15 This study sought to compare the anesthetic efficacy and the success rate of lidocaine and epinephrine with the same local anesthetic combination plus dexamethasone for IANBs in teeth with SIP.

Evidence suggests that nociceptor priming because of the presence of inflammatory mediators is a major cause for decreased success rates of local anesthesia in patients with irreversible pulpitis.^1,5,16–19 Glucocorticoids act by inducing the formation of lipocortins (phospholipase A2 inhibitory proteins), potent anti-inflammatory agents that suppress the formation of arachidonic acid from cell membrane phospholipid metabolism, preventing subsequent activation of the cyclooxygenase and lipoxygenase pathways and the respective synthesis of inflammatory mediators like prostaglandins and leukotrienes.^20,21 Glucocorticoids act to suppress vasodilation, edema, migration of polymorphonuclear leukocytes, and phagocytosis. Clinically, the intraosseous injection of glucocorticosteroids like methylprednisolone have reportedly temporarily reduced the symptoms of irreversible pulpitis.²² A systematic review reported success for pulpal anesthesia in patients with irreversible pulpitis when premedicated with dexamethasone.²³

Some studies have suggested that buccal infiltration of dexamethasone reduces tissue inflammation and improves the efficacy of IANBs in teeth with irreversible pulpitis.⁷ Additionally, the onset time of sensory and motor blocks has been reported to be significantly reduced with the addition of dexamethasone to lidocaine.²⁴ Bhargava et al²⁵ recommended mixing of a glucocorticoid steroid and a local anesthetic for combined use as a single injection for third molar extractions and reported a high success rate for pain control. As the conventional IANB technique delivers both drugs together in a single injection, there is no need to utilize additional clinical techniques to administer this admixture.

The addition of dexamethasone to lidocaine with epinephrine for an IANB increases the pH of the local anesthetic solution. This raises the concentration of free-base local anesthetic molecules available to cross the cell membrane, decreasing the onset time. The increased pH also leads to decreased pain or burning upon injection.⁹ A study by Mackinnon et al²⁶ demonstrated that dexamethasone causes minimal peripheral nerve damage after injection unlike hydrocortisone and triamcinolone. Furthermore, although there may be concern about healing after the use of corticosteroid, Thorén et al²⁷ found no augmented risk of delayed healing with dexamethasone doses ≤30 mg or an equivalent.

The success of IANB is assessed using a variety of different signs such as lip numbness,¹³ visual analogue scales,^28,29 and lack of response to cold^13,29 or electric stimuli (EPT). In the present study, 100%of patients reported lip numbness. However, although a lack of lip numbness can be an indicator of a missed block, lip numbness does not guarantee pulpal anesthesia.^30–32 Therefore, once lip numbness was noted, pulpal anesthesia was further assessed via EPT. A lack of patient response to EPT was used to identify likely pulpal anesthesia prior to endodontic access and file placement. However, for this study successful anesthesia was defined by being able to complete access to the pulp and place files in the root canals with the patient experiencing no pain or mild pain (HP-VAS score 0 or 1). Nusstein et al³³ used EPT as an indicator for successful anesthesia in IANB for teeth with irreversible pulpitis and reported that 42% of patients with negative EPT still experienced pain during access and instrumentation. Comparable to their findings, in this study 32% of the Twin mix group and 34% of the lidocaine group experienced pain. The use of a second anesthetic delivered a greater weight/volume percentage of drug, leading to improved outcome.

Though some authors suggest that the concentration of vasoconstrictors influences the success of IANB,³⁴ others contradict it.³⁵ In the present study, 1:200,000 epinephrine was selected over the more traditional 1:100,000 because 1:200,000 concentration of epinephrine provides results comparable to 1:100,000 with fewer systemic side effects.³⁶ Also, Twin mix has been customarily prepared with 1:200,000 epinephrine formulations.⁹

In this study, pulpal anesthesia achieved by Twin mix and lidocaine was 87% and 89%, respectively. These values were higher than previously conducted studies by Visconti et al⁶ and Tortamano et al,³⁷ where the pulpal anesthesia with lidocaine was 67% and 70%, respectively. The IANB success rate using Twin mix and lidocaine for teeth with SIP during endodontic access and instrumentation was 68% and 66%, respectively. The success achieved by both groups was comparable, and the difference not statistically significant. These values are higher than studies performed by Visconti et al⁶ and Tortamano et al,³⁷ where the IANB success rates were 14% and 45%, respectively. Mehrvarzfar et al³⁸ concluded that corticosteroids must be present at the site of inflammation to exert their anti-inflammatory action. In this study, dexamethasone was used as IANB and not as an infiltration at site of inflammation, which could explain the lack of superiority of Twin mix over standard lidocaine with epinephrine for IANBs.

CONCLUSION

The primary outcome of the study was that the anesthetic efficacy of Twin mix was equivalent to 2% lidocaine with 1:200,000 epinephrine for IANB in teeth with SIP. Within the limitations of this study, the use of dexamethasone combined with 2% lidocaine with 1:200,000 epinephrine (Twin mix) for IANB in patients with SIP is not recommended.