Enhanced Analgesic Outcomes with Low-dose Dexmedetomidine and Lignocaine–Adrenaline in Pediatric Inferior Alveolar Nerve Block: A Randomized Trial

Abstract

Aim and background

The present double-blind randomized trial was conducted to evaluate if dexmedetomidine enhances the effect of lignocaine-induced local anesthesia in 4–8-year-old children undergoing mandibular molar pulpectomies.

Materials and methods

This double-blind randomized controlled trial included 60 pediatric patients scheduled for mandibular molar pulpectomy, who were allocated into 2 groups. In group A (n = 30), inferior alveolar nerve block was administered with 2% lignocaine containing adrenaline (1:2,00,000), whereas group B (n = 30) received the same solution supplemented with a low dose of dexmedetomidine (0.5 µg/kg). The primary variable assessed was intraoperative pain, evaluated through the Wong–Baker Faces Pain Rating Scale and the FLACC (Face, Legs, Activity, Cry, and Consolability) scale. Secondary variables comprised commencement and persistence of anesthesia, sedation levels, and vital signs. Data analysis was performed using independent t-tests, with statistical significance set at p < 0.05.

Results

Children administered the dexmedetomidine–lignocaine combination demonstrated lower pain scores than those who received lignocaine alone, as shown by the Wong–Baker scale (p = 0.009) and the FLACC scale (p = 0.025). Furthermore, the onset of anesthesia occurred in a shorter duration, and the effect persisted longer with the dexmedetomidine–lignocaine combination (p = 0.001). No sedative effects were observed, and all physiological parameters remained stable in both groups of participants.

Conclusion

The low-dose dexmedetomidine successfully enhanced the effect of lignocaine by providing faster and enhanced anesthesia for better pain control.

Clinical significance

Incorporating low-dose dexmedetomidine with lignocaine in pediatric pulpectomies enhances local anesthetic efficacy by reducing pain, shortening onset, and prolonging duration of anesthesia. This combination offers a safer and more comfortable treatment experience for young children.

Introduction

Pain control during pediatric dental procedures is a significant concern in pediatric dentistry, especially when behavioral challenges are present.¹ Exposure to even minimal amount of pain in dental settings can affect the behavior and cooperation of children, precluding the successful completion of dental treatment efficiently.^2–4 Further, the child who experiences pain in first visit may be reluctant to provide cooperation in subsequent visits as well.^2,3 Henceforth, it is understood that effective pain control not only ensures that the child is more comfortable but also enhances compliance with dental procedures.

The nerve blocks are most commonly employed methods to achieve pain control and anesthesia in dentistry. Among the various techniques, the inferior alveolar nerve block (IANB) is one of the commonly administered blocks for obtaining profound local anesthesia in the mandible. Traditionally, local anesthetics such as lignocaine combined with adrenaline are used to induce anesthesia and maintain its duration.¹ However, children often exhibit increased apprehension and lower pain tolerance in relation to adults, complicating the administration of local anesthesia.⁵ This necessitates measures to compound the effect of local anesthetics by various additives.^6,7 A few reports have shown that addition of dexmedetomidine can potentiate the effect of lignocaine.^8–11

Dexmedetomidine, an α2 receptor agonist of marked specificity with sedation-producing, anxiolytic, and pain-relieving actions,^12,13 has gained popularity in recent years, as few studies have suggested its potential as an adjunct to local anesthesia in offering earlier initiation, longer duration of action, and efficient pain control.^8,11,14,15 Co-administering the 2 allows for parity of analgesic effects with respiratory safety and is therefore ideal in a pediatric population. However, there is hardly any evidence to support these findings in pediatric population in dental settings. Closing this knowledge gap is instrumental in enhancing pain control methods, which have immense clinical and patient-related effects in pediatric dentistry.

Keeping in mind the above facts, the present double-blind, randomized controlled trial was planned to investigate if low-dose dexmedetomidine can enhance the effect of lignocaine-adrenaline IANB in children aged 4–8 years scheduled for molar pulpectomies. By looking at a number of variables, such as initiation of anesthesia, effective period, pain scores, and cooperation during surgery, this study hopes to clarify whether dexmedetomidine improves perioperative pain control.

The results of this study are anticipated to establish a basis for the effective use of dexmedetomidine by investigating its synergistic interaction with conventional local anesthetic agents in enhancing pediatric dental pain control and hence improving care rendered to young patients.

Materials and Methods

Study Design and Settings

The present randomized controlled trial aimed to intercompare efficacy of low-dose dexmedetomidine in addition to lignocaine with adrenaline-induced anesthesia (intervention group) for IANB and conventional lignocaine with adrenaline-induced anesthesia (baseline/control group) IANB in 4–8-year-olds undergoing mandibular molar pulpectomy. The research was carried out in outpatient unit of Department of Pediatric and Preventive Dentistry in a dental training facility. The study was conducted from June 2022 to December 2022.

Study Objectives

The primary aim of this research involved comparing pain intensity between groups using the Wong–Baker Pain Scale.¹⁶ Additional aims included evaluating patient cooperation through the FLACC scale¹⁷ (Face, Legs, Activity, Cry, and Consolability), determining the onset and duration of anesthesia, monitoring vital parameters such as heart rate, noninvasive blood pressure, respiratory rate, and oxygen saturation (SpO₂), and recording any adverse events.

Study Population

The study sample comprised of 60 subjects (30 participants per group). The sample size was calculated by assuming clinical difference of 1 in pain scores as measured by Wong–Baker scale (primary outcome), a standard deviation of 1.3, a significance level (α) of 0.05, and a power (1−β) of 80%. A total of 30 participants was needed for each group. We did not optimize the sample size for potential dropouts, as each study subject was required to be observed only on the day of the procedure.

The eligibility criteria were children aged 4–8 years scheduled for mandibular molar pulpectomy with ASA physical status I or II. Parental/guardian written informed consent was mandatory requisite for enrollment in the study. Children with allergy to local anesthetics or dexmedetomidine, history of significant medical conditions affecting the study outcomes, children with special health care needs, abscess at the planned site of intervention, and children with Frankl definitely negative behavior rating did not participate in this research.

Randomization

Participants were placed into 2 groups using a randomization sequence generated online using www.graphpad.com/prism.

Group A (control/baseline): Lignocaine with adrenaline.

Group B (intervention): Lignocaine with adrenaline plus low-dose dexmedetomidine.

The sequence for random assignment was kept confidential until participants received their designated interventions. The personnel responsible for enrolling participants did not have access to the allocation sequence.

Blinding

The operator performing the dental procedures was blinded to the group allocations. An independent assistant prepared and provided the anesthetic solutions. The syringes were covered with opaque tape to avoid identification by visual observation. The syringes were loaded with solution prepared as per weight of child by a trained pediatric dentist not further involved in administration of local anesthesia and operative intervention.

Anesthetic Solutions

Group A: 2% lignocaine with 1:2,00,000 adrenaline (Xylocaine, Zydus Cadila, India).

Group B: 2% lignocaine with 1:2,00,000 adrenaline plus dexmedetomidine (Xamdex, Abbott Pharmaceuticals, India) at a dose of 0.5 µg/kg.

Procedure

All steps in both of the study groups, intervention as well as control, were carried out by single operator to avoid introduction of confounding factors. All study participants in both of the groups received routine behavior management as provided to all children in our clinics such as tender loving care, tell show do, and modeling. Topical anesthesia (2% lignocaine jelly) was applied at the site of administration of local anesthesia using cotton swab. The local anesthesia was administered using 26-gauge disposable syringe. The pulpectomy was performed in a routine standardized manner using rotary files under rubber dam isolation by single experienced pediatric dentist.

Preoperative Assessment

Baseline physiological parameters (heart rate, blood pressure, respiratory rate, and SpO₂ levels).

Administration of Anesthesia

Group A: 2% lignocaine with 1:2,00,000 adrenaline was delivered for inferior alveolar nerve block (IANB).

Group B: 2% lignocaine with 1:2,00,000 adrenaline plus low-dose dexmedetomidine was delivered for IANB.

Monitoring

The time of onset together with the span of anesthesia were documented. The time for initiation of anesthesia was described as time from administration of anesthesia till the lack of sensation was confirmed in gingival tissue surrounding tooth by operator using blunt explorer. The effective period of anesthesia was documented as the interval until the return of sensation using same tactile method. Pain during the procedure was evaluated using the Wong–Baker Pain Scale and FLACC Pain Scale. The assessment of sedation was done using Ramsay Sedation Scale from administration of local anesthesia to 30 minutes following its administration. Vital signs were monitored continuously during the procedure using the pulse oximeter, and recording on preprinted pro formas was done every 5 minutes.

Postoperative Assessment

The duration of postoperative analgesia was noted for 1 hour. The requirement for additional analgesic medicine was also noted.

Statistical Analysis

Data analysis was performed using SPSS software, version 27.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics were applied to present demographic and clinical variables as mean ± standard deviation or as frequencies with percentages. Independent t-tests were employed to assess differences in time to initiation of anesthesia, effective period of anesthesia, pain scores, and posttreatment analgesic effect between the 2 groups. Statistical significance was set at p < 0.05.

Results

Sixty-six subjects met the eligibility criteria for this research, out of which 60 participants were randomized into the 2 study groups (Fig. 1). The baseline demographic characteristics of both of the study groups were statistically equivalent (p > 0.05; Table 1). The intervention group exhibited a significantly faster onset of anesthesia and a significantly prolonged duration of anesthetic effect compared with the baseline group (p = 0.001; Table 2). Further, participants in the intervention group reported significantly reduced pain levels compared to the control/baseline group, as depicted by Wong–Baker scale (p = 0.009), and FLACC scale (p = 0.025) depicted higher comfort levels in intervention group (Table 3). Only 1 of the study subjects needed additional analgesia in postoperative observation period of 1 hour. No sedative effects were noted in intervention group (Table 4). Lastly, at all time points of observations, statistically similar differences (p > 0.05) were observed between the 2 study groups for vital sign parameters such as heart rate (Fig. 2), blood pressure (Fig. 3), respiratory rate (Fig. 4), and SpO₂ levels (Fig. 5).

Fig. 1.

Flow of participants in the study

Table 1.

Demographic characteristics of the participants

Characteristic	Group A (control)	Group B (intervention)	p-value
Number of participants	30	30	−
Age (years)	7.9 ± 1.31	7.4 ± 1.52	0.18#
Gender (M/F)	12/18	13/17	0.79!
Weight (kg)	22.6 ± 3.27	23.1 ± 3.68	0.58#

^#Calculated using independent t-test; ^!Calculated using Chi-squared test

Table 2.

Onset and duration of anesthesia

Parameter	Group A (control)	Group B (intervention)	p-value #
Onset of anesthesia (seconds)	164.65 ± 12.37	131.27 ± 11.91	0.001*
Duration of anesthesia (minutes)	123.55 ± 27.55	167.60 ± 22.50	<0.001*

^#Calculated using independent t-test; *Statistically significant p-value

Table 3.

Pain scores during the procedure

Pain Scale	Group A (control)	Group B (intervention)	p-value #
Wong–Baker (0–10)	2.1 ± 1.37	1.2 ± 1.19	0.009*
FLACC (0–10)	2.4 ± 1.43	1.6 ± 1.24	0.025*

^#Calculated using independent t-test; *Statistically significant p-value

Table 4.

Sedation levels (Ramsay sedation scale)

Time point (minutes)	Group A (control)	Group B (intervention)	p-value #
5	1.2 ± 0.47	1.3 ± 0.53	0.28
10	1.1 ± 0.32	1.2 ± 0.47	0.4
15	1.1 ± 0.21	1.2 ± 0.42	0.37
30	1 ± 0.15	1.2 ± 0.36	0.20

^#Calculated using independent t-test

Fig. 2.

Variation in heart rate at various time points of observation

Fig. 3.

Variation in blood pressure at various time points of observation

Fig. 4.

Variation in respiratory rate at various time points of observation

Fig. 5.

Variation in oxygen saturation at various time points of observation

Discussion

Efficient pain control is an important aspect of optimizing patient satisfaction in dental treatment. This is especially true in pediatric dentistry, where heightened anxiety and lack of emotional maturity further necessitate profound anesthesia and pain control.^1,18 Lignocaine in combination with adrenaline is one of the most commonly used anesthetic solutions to provide anesthesia and pain control in dentistry.¹⁹ A substantial amount of research has been conducted in past to potentiate the effect of lignocaine by using adrenaline, buffers such as bicarbonate, magnesium ions, nonsteroidal antiinflammatory drugs (NSAIDs), morphine, fentanyl, sulfentanil, and other agents.⁶ Adrenaline, the most widely used additive, is a natural vasoconstrictor and hence should be used cautiously in individuals with cardiovascular conditions.²⁰ Also, it has potential neurotoxicity, as it compromises endoneurial blood flow.²¹ This can precipitate neuropathy, and the same has been substantiated in rat model study. However, none of these measures could achieve wide acceptance.

Adrenaline is a natural vasoconstrictor and should be used cautiously in patients with cardiovascular compromise.²⁰ Also, it has potential neurotoxicity, as it compromises endoneurial blood flow.²¹ This can precipitate neuropathy, and the same has been substantiated in rat model study. Recent studies have provided evidence regarding the potential for dexmedetomidine to serve as an adjunct to lignocaine in enhancing anesthesia and pain control.^9,10,14,15

Dexmedetomidine is reported to act as a potential supplementary agent with local anesthetics, prolonging the duration of action and enhancing anesthesia.²² It is highly selective α2 clonidine receptor agonist with analgesic, sedative, and anxiolytic actions.^12,13 The plausible mechanism of enhancing the effect of local anesthesia by dexmedetomidine is local vasoconstriction with decrease in perineural inflammation.²³ It also affects the pH of the solution. It provides faster induction of anesthesia, an extended period of effect, and enhanced pain relief.^10,15 Although the mechanism of analgesic effect is not yet completely proven, there are a few in vitro reports that substantiated that it inhibits C-fiber action potential and Na+ channels in neurons. Further, it inhibits the central nociceptive pathways by activating α2 adrenoreceptors in locus coeruleus.¹²

Initial exploration of the potential of dexmedetomidine as a supplementary agent with local anesthesia proved its efficacy for sciatic nerve blocks in combination with ropivacaine and bupivacaine in rat model.^24,25 Further studies on human volunteers proved that dexmedetomidine as a supplementary agent with local anesthesia provided faster induction of anesthesia and extended period of action for nerve block in combination with ropivacaine and levobupivacaine for ulnar nerve block and spinal nerve block, respectively.^10,26 A handful of studies have evaluated dexmedetomidine's role in dental settings for IANB, infraorbital nerve block, and local infiltration for dental extraction and management of irreversible pulpitis. However, none evaluated its role in pediatric population.^{14,15,27–31}

To the best of our knowledge, this is among the first studies to evaluate the effectiveness of adding low-dose dexmedetomidine to lignocaine for IANB in pediatric patients undergoing molar pulpectomy. The principal aim was to investigate if dexmedetomidine enhances the efficacy of the routinely used local anesthetic, lignocaine with adrenaline, in achieving superior pain control in pediatric dental treatment.

Throughout the course of this research, methodological robustness was ensured. The randomization and operator blinding procedures reduced the likelihood of selection bias or performance bias.³² Standardized pain assessment tools, the Wong–Baker FACES Pain Rating Scale and FLACC Pain Scale score, were used to keep objective measurement of procedural pain. Careful continuous monitoring of vital parameters was performed in order to assure the safety of subjects as well as accurate data capture. Sample sizes were adequately powered across the intervention and baseline groups to identify significant variations, thereby strengthening validity. A single clinician carried out all procedures to reduce the introduction of confounding factors.

The findings of the present study emphasize many advantages of adjuncting lignocaine with adrenaline with low-dose dexmedetomidine for IANB in pediatric mandibular molar pulpectomies. With addition of dexmedetomidine, the induction period was reduced, and action of anesthesia lasted longer. The increase in duration of anesthesia resulted in an increased total time during which pain is relieved, and these findings are in accordance with earlier research in the field of dentistry.^14,15,28

Pain scores during the procedure, measured using both the Wong–Baker FACES Pain Rating Scale and the FLACC Pain Scale, were significantly lower in the intervention group compared to the control group. This suggests that dexmedetomidine enhances the analgesic effect of lignocaine and adrenaline, leading to better intraoperative pain control, and these findings are in line with previous research on dexmedetomidine as an adjuvant to local anesthesia.^29,30

The duration of postoperative analgesia was significantly longer in the dexmedetomidine group, and this was in corroboration with previous research in dental settings.^14,15,27,29 This extended period of pain relief postprocedure can reduce the need for additional analgesic interventions, improving patient comfort and potentially decreasing the overall analgesic burden. This was substantiated by findings of the present study as well.

Although heart rate and blood pressure were slightly reduced in the intervention group relative to the baseline group, these minimal differences were neither clinically nor statistically significant.

The effects of dexmedetomidine on heart rate and blood pressure are due to its known sympatholytic and anxiolytic properties. These hemodynamic changes imply minimal physiological stress and anxiety, which is useful during dental procedures. The respiratory rate and peripheral oxygen saturation were similar in both groups, and neither gas nor dexmedetomidine increased airway resistance. The minimal changes were seen because of very low dose used in the current study. Previously published literature also reported no >20% fluctuation in vital parameters upon coadministration of dexmedetomidine with local anesthesia.^14,28,30

This paper is a further exploration regarding dexmedetomidine as a supplementary agent with local anesthetics in pediatric dental treatment. The increase in anesthetic depth with better pain control clearly enhanced the patients' experience, as they became more comfortable during dental treatments. The consistency of cardiovascular stability with dexmedetomidine additionally confirms its safety profile and further supports reasons for its incorporation into the armamentarium of pediatric dental anesthesia.

Although the present study was conducted with methodological rigor, the findings are based on a single institutional experience. Similar results may also be achieved in other clinical practice settings. However, more of these types of studies involving racially as well as geographically diverse populations and different scenarios are required for confirmation.

We recommend that future research investigate the safety and efficacy of this combination in larger, more heterogeneous pediatric populations over longer periods. Further research investigating the ideal doses of dexmedetomidine and its efficacy in dental procedures of different types is required. In addition, it would be interesting to evaluate the potential of dexmedetomidine alongside other local anesthetic agents, as well as on different pain management pathways, given its potential implications for broader clinical use.

Conclusion

The results of this research suggest that low-dose dexmedetomidine enhances the anesthetic effects of lignocaine with adrenaline and offers improved pain control for pediatric patients undergoing mandibular molar pulpectomies. The results highlight the effectiveness of dexmedetomidine as a beneficial adjunct in pediatric dental anesthesia. However, future multicentric trials in varied settings are needed to add more evidence to support the routine application of dexmedetomidine alongside local anesthesia in pediatric dental settings.

Clinical Significance

This study highlights that adding low-dose dexmedetomidine to lignocaine significantly improves local anesthetic performance in pediatric dental procedures. Children experienced faster onset, extended period of anesthesia, and lower pain levels without any adverse sedative effects or changes in vital signs. These findings suggest a safe and effective modification of routine local anesthesia that can improve cooperation and comfort during pulpectomies. Incorporating this approach may enhance overall treatment outcomes in pediatric dentistry.

Ethical Considerations

The ethical clearance for the study was provided by Institutional Ethics Committee and review board (via letter number SU/2021-22/1300/48). Written informed consent was obtained from the parents or guardians of all participating children. The study adhered to ethical principles for research on human and biomedical subjects by Indian Council of Medical Research.

Author Contributions

Dr Neeti Mittal was chief investigator and responsible for ideation, conduction of study, and drafting manuscript; Dr Nidhi Gupta was responsible for data management and manuscript editing; Dr Sreelakshmi Jayalal was responsible for coordination for study and manuscript editing. All authors read and approved the final draft.

Acknowledgments

The research group sincerely expresses gratitude to the children and parents for participating in the research. The authors further express their appreciation to all departmental staff for their valuable support. Institution to which the work should be credited: Santosh Deemed to be University.

AI Disclosure

ChatGPT (OpenAI) was used solely for language editing, including grammar correction and rephrasing of the manuscript. The authors reviewed, revised, and approved all content and take full responsibility for the accuracy and integrity of the final manuscript.

Orcid

Neeti Mittal https://orcid.org/0000-0002-7866-5091

Nidhi Gupta https://orcid.org/0000-0002-1900-8622

Sreelakshmi Jayalal https://orcid.org/0009-0003-8064-4198

Data Availability Statement

Anonymized participant information, accompanying data dictionary, analysis scripts, and study resources cannot be accessed openly owing to confidentiality and moral constraints. However, these can be provided upon justified request by contacting the corresponding author, Prof. (Dr) Nidhi Gupta (email: nid_gup6@yahoo.co.in).