Investigating the Efficacy of Dexmedetomidine as an Adjuvant to Local Anesthesia in Dentistry: Systematic Review and Meta Analysis

Investigating the Efficacy of Dexmedetomidine as an Adjuvant to Local Anesthesia in Dentistry: Systematic Review and Meta Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Investigating the Efficacy of Dexmedetomidine as an Adjuvant to Local Anesthesia in Dentistry: Systematic Review and Meta Analysis Salah Ameen Abdu, Wafa Ali Asaad, Tao Wei, Muaadh Wdaan, Wendong Wan, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5597524/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background and Objectives: Dexmedetomidine has been considered an effective adjunct to dental local anesthetics. Uncertainty about its efficacy and safety in dental use still remains. This study is primarily designed to evaluate the effectiveness and safety of dexmedetomidine as an adjunct to local anesthesia in dental procedures. Methods: A meta-analysis of controlled trials assessed the effects of dexmedetomidine as an adjunct to local anesthesia in dental procedures, focusing on anesthesia duration and onset time. Studies were identified via multiple databases, and methodological quality was evaluated using ROBINS-I and Cochrane Risk of Bias tools. RevMan V.5.1 was used for heterogeneity analysis, sensitivity analyses, pooling mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CI), and assessing publication bias. Results: This meta-analysis included sixteen clinically controlled trials involving 658 patients ( n =877 samples). Adding dexmedetomidine significantly reduced onset time by 48.78 seconds (95 % CI : -64.22 to -33.35 seconds) and prolonged analgesia duration by 31.10 minutes (95 % CI : 13.77 to 48.43 minutes). It also significantly increased postoperative analgesic duration by 186.19 minutes (95 % CI : 109.09 to 263.29 minutes). Hemodynamic analysis revealed non-significant changes in heart rate, intraoperative systolic and diastolic pressures, and oxygen saturation. It is important to note that minor heart rate and blood pressure fluctuations did not lead to clinically significant hypotension or bradycardia during dental procedures. Conclusions: Dexmedetomidine enhances dental local anesthesia by providing quicker onset, longer duration, improved postoperative pain management, and a favorable safety profile, though further research is needed to address variability. Dexmedetomidine Local anesthesia Dental procedures Nerve block Adjuvant anesthetics Anesthetic efficacy Pain management Meta-analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Introduction Effective postoperative pain control is an integral part of patient care in dentistry, especially for procedures such as third molar extractions, which are known to be significantly painful postoperatively [1–3]. Local anaesthesia forms the main modality of pain management in dental surgery; however, it suffers from drawbacks related to a very limited duration of action and systemic toxicity with larger doses of local anaesthetics [4]. Consequently, the search for adjuvants that enhance the quality and duration of anesthesia and analgesia with a reduction of adverse effects has been continued [4]. Dexmedetomidine (DEX) is an α2-adrenergic receptor agonist that has demonstrated high selectivity and appeared as an effective adjuvant to extend the action of local anesthetics [5–10]. DEX possesses analgesic, anxiolytic, and sedative effects with minimal respiratory depression [5–7, 9, 11–14]. When used with local anesthetics, DEX can prolong analgesia duration, reduce postoperative pain scores, and reduce the need for rescue analgesics [5–12, 15, 16]. The application of DEX as an adjuvant with local anaesthesia has become a subject of interest in dentistry; however, there is still a need for an overview regarding efficacy and the profile of this drug's safety. Numerous systematic reviews and meta-analyses were performed to outline the role of DEX in regional anesthesia techniques, such as peripheral nerve blocks, neuraxial blocks, and intravenous regional anesthesia [5–8, 10, 11, 17, 18]. However, there is limited conclusive evidence regarding its application in dentistry, and the optimal dosage for dental purposes is not clearly specified [5, 6, 10, 15, 19, 20]. Furthermore, while generally considered safe, DEX can cause haemodynamic changes, such as bradycardia and hypotension [3, 12, 15, 16]. The potential effect of DEX in modifying the parameters of haemodynamics becomes relevant in dental settings, where the majority of procedures are day-care surgeries and demand quick recovery with minimal side effects [3, 9]. Although several studies have explored the hemodynamic effects of DEX as an adjuvant to local anaesthesia in dentistry, the results were conflicting [3, 4, 9, 13, 19–25]. Therefore, the primary objective of our systematic review and meta-analysis is to assess whether dexmedetomidine prolongs the duration of dental nerve blockade as an adjuvant to local anesthesia compared with the use of local anesthesia alone (control) in adult patients ≥ 10 years of age undergoing dental procedures. We further want to elaborate on the adverse events profile of dexmedetomidine in order to understand its safety. Methods The PRISMA methodological approach was adopted in the present study to systematically conduct the review and meta-analysis. It, therefore, provided a systematic guide on the identification, evaluation, and synthesis of studies in a manner that made the review as transparent and reproducible as possible. In line with the PRISMA guidelines, we set out to provide a comprehensive overview of the available evidence with respect to the effectiveness and safety of dexmedetomidine as an adjunct to local dental anesthesia [26]. Criteria for Study Inclusion and Exclusion Our systematic review and meta-analysis focused on clinical trials that evaluated dexmedetomidine as an adjunct to local anaesthesia in adults (≥ 10 years) undergoing oral procedures. Only studies using local anaesthesia were included to maintain consistency and minimise the high level of expected heterogeneity. The choice of local anaesthetic and its dosage and the specific dose of dexmedetomidine were not considered for inclusion. The articles published in English are included in this systematic review and meta-analysis. Studies primarily investigating dexmedetomidine's effect on dental pulpal anaesthesia were excluded. Identification of Relevant Studies An experienced evidence-based medicine librarian (TW) developed a comprehensive search strategy, including both published and unpublished studies, across multiple databases: MEDLINE, EMBASE, Cochrane Library, Ovid, Web of Science and Google Scholar. The title of each search result after January 2014 to November 4, 2024, was meticulously screened by two independent reviewers, SAA and WAA. First of all, screening was done in duplicate based on title and abstract. Following that, all the potentially qualified articles would undergo a full-text review to confirm their eligibility for inclusion. During this time, any discrepancies arising between these three reviewers were resolved through collaboration by discussion to a consensus. In case there was no consensus through discussion, an independent third reviewer's (NL) evaluation provided an assessment of the disagreement. Lastly, the bibliographies and citations of all the included articles were carefully scanned to ensure the comprehensiveness of the search strategy regarding any missed studies. Outcomes Assessed The primary outcomes of our meta-analysis were to compare the onset and duration of dental local nerve blockade with the addition of dexmedetomidine versus control. The secondary outcomes of this review were overall postoperative pain at 12–24-hour follow-up, duration of analgesia, postoperative analgesic consumption, and adverse events. The adverse events included in this meta-analysis were hypotension (systolic and diastolic blood pressure), oxygen saturation, and heart rate. These were selected because they were commonly reported by involved studies and were considered to be clinically important. Data Management and Extraction A data extraction form was designed and then piloted by an independent reviewer (SAA). The data extraction form collected information regarding the clinical setting, demographics, outcome data (eg, onset of anesthesia, duration of anesthesia), and adverse events. Two independent reviewers (SAA, WAA) extracted data to ensure accuracy and minimize risk of error. In the case of a disagreement in data extraction, the 2 reviewers discussed until a consensus was reached. If a consensus still could not be reached, a third reviewer (NL) was tasked with making the final decision. The study characteristic Methodological Quality Assessment Process Two independent reviewers (Salah and Wafa) conducted the methodological quality assessment of the included studies. The Revised Cochrane Risk-of-Bias tool (RoB 2) was used to evaluate the 14 randomized controlled trials across five domains, with risk levels categorized as high (red), unclear (yellow), or low (green) [27]. The ROBINS-I tool assessed the 2 non-randomized studies across seven domains, with risk levels designated as serious (dark red), critical/high (red), moderate (yellow), or low (green) [28]. An unweighted kappa statistic was calculated to evaluate initial interrater agreement. Disagreements between reviewers were resolved through discussion, and when consensus couldn't be reached, a third reviewer (TW) was consulted for final decision-making. Meta-Analysis and Heterogeneity Assessment This meta-analysis was carried out using Review-Manager software provided by the Cochrane Collaboration (RevMan V.5.1). Binary outcome data were pooled and expressed as risk ratios ( RR ) with confidence intervals ( CI ) of 95%. Continuous outcome data were pooled using mean difference (MD) with confidence intervals ( CI ) of 95 % . The Chi- square test was used with the Mantel-Haenszel method ( I 2 ≥ 50 % , P ≤ 0.1) to determine the heterogeneity of the included studies. Looking for possible reasons for heterogeneity, subgroup and sensitivity analyses were performed. A random-effects model (DerSimonian and Laird method) was adopted when statistical or clinical heterogeneity was assessed as high, considering the variability among studies. A P value of ≤ 0.05 was established as the significance level for reporting the overall effect size. With a low heterogeneity, a fixed-effects model was used to evaluate the assumed common underlying treatment. Results Study Characteristics At first, a literature search identified a total of 1220 articles. Ninety-seven articles were assessed as a primary result for initial screening. After screening the title and abstract, 23 articles were assessed for full-text eligibility. Of these articles, 16 articles were included in this meta-analysis, seven articles were excluded because of their age < 10 [29–32], article review [33], and dental pulp studies[14, 34]. The full-flow diagram of study inclusion is shown in (Fig. 1 ). A comprehensive overview of all included studies is presented in Table 1. All studies were published between 2014 and 2024. Across all included studies, 658 patients (877 samples) were assessed. Regarding the technique of local anesthetic used, a total of 15 studies utilized nerve block [2–4, 13, 19–24, 35–39], 11 mainly used an inferior alveolar [2, 3, 13, 19–22, 35, 36, 38, 39], while 4 study used infraorbital nerve block and inferior alveolar nerve block [4, 23, 24, 37]. Dexmedetomidine was used as an adjuvant to three different local anesthetics, which included lidocaine [2–4, 13, 19–24, 36, 37, 39, 40], levobupivacaine [35], ropivacaine [38]. Across the studies, the dose of dexmedetomidine ranged from 1 µg to 15 µg , and the dosages of local anesthetics varied among the studies. Figure 1 Diagram illustrates the complete process of study inclusion. Table 1 offers a comprehensive overview of all studies included in this meta-analysis. Bias assessment After bias assessment, the 14 RCTs assessed with RoB 2 mostly showed low bias (green), but some had high bias (red) in blinding [13, 21, 35] and unclear bias (yellow) in selective reporting or other domains. For the 2 non-randomized studies using ROBINS-I, Priyaranjan et al had critical/high bias (red) in confounding and selection, while Kosar et al showed low bias overall with moderate bias (yellow) in selective reporting. Overall, the RCTs had fewer bias concerns than the non-randomized studies. For more information the bias assessment of included studies was clarified in Fig. 2 a, 2 b. Figure 2 a Assessment of bias for all randomized trials included in in this study. Figure 2 b Assessment of bias for both nonrandomized trials included in this study. Onset of Anesthesia Figure 3 (a) Mean onset time for nerve blockade in seconds with 95% CI for dexmedetomidine versus control. Figure 3 b Subgroup mean onset time for maxillary and mandibular nerve blockade with 95% CI for dexmedetomidine. Figure 3 c Subgroup mean onset time for nerve blockade in seconds with 95% CI for dexmedetomidine 1µg/ml. Figure 3 d Subgroup mean onset time for nerve blockade in seconds with 95% CI for dexmedetomidine compared to lidocaine. Of 16 studies, 12 ones assessed the onset time of anesthesia; however, eight studies ( n = 560) had sufficient information to allow for pooling [4, 21–24, 35, 37, 38]. The addition of dexmedetomidine significantly decreased the onset time of anesthesia of nerve blockade by an average of -48.78 seconds in comparison to the control (95 % CI : -64.22 to -33.35; I = 95 % ), favouring dexmedetomidine, with a highly significant overall effect ( Z = 6.20, p < 0.00001) (Fig. 3 a). Subgroup analyses were performed because the heterogeneity was above our predefined cutoff. Studies were grouped according to mandibular comparing to maxillary anesthesia (Fig. 3 b), dexmedetomidine concentration1 µg/mL (Fig. 3 c), and lidocaine (Fig. 3 d). The mandibular anesthesia meta-analysis mean difference was − 47.94 seconds (95% CI : -74.01 to -21.86), showing a faster onset favouring dexmedetomidine. Heterogeneity was high ( I² = 98%). Maxillary Anesthesia mean difference was − 49.88 seconds (95 % CI : -63.76 to -35.99), with significant efficacy in reducing onset time and slightly high heterogeneity ( I² = 62 % ). While the subgroup for one µg/mL dexmedetomidine showed a mean difference of -43.72 seconds (95% CI : -59.69 to -27.76). This consistent improvement underlines the effective concentration used, though with high heterogeneity ( I² = 94%). It was even stronger when put in relation to lidocaine, and the mean difference was − 49.09 seconds (95% CI : -60.11, -38.08). The heterogeneity was lower than the others, with I² = 83 % , indicating some variability yet a strong general effect. Duration of Anesthesia Figure 4 Mean duration of nerve blockade in minutes with 95% CI for dexmedetomidine versus control patients. Out of 16 studies, 13 revealed the duration time of anesthesia, but only seven studies had sufficient information to allow for pooling [2, 4, 20, 22, 24, 36, 37]. The meta-analysis compiled data from the seven studies involving 534 patients, with 267 assigned to the dexmedetomidine group and 267 to the control group. The pooled results showed a mean difference of 31.10 minutes (95 % confidence interval: 13.77 to 48.43) in favour of the dexmedetomidine group. The findings were statistically significant, with a Z -value of 3.52 and a p -value of 0.0004. However, the meta-analysis showed significant heterogeneity among the included studies, with an I² value of 94 % (Fig. 4 ). This high degree of heterogeneity suggests that there might be significant changes in methodology, type of local anaesthetics used, study designs, and patient demographics—all elements that could affect results. Analgesic Duration Figure 5 Mean duration of postoperative analgesia in minutes with 95% CI for dexmedetomidine versus control patients. The meta-analysis synthesized findings from four studies [2, 21, 23, 35] involving 270 patients—135 in the dexmedetomidine group and 135 in the control group. Each study measured the duration of analgesia following the administration of dexmedetomidine alongside conventional local anesthetics. The dexmedetomidine group and the control group mean difference in analgesia duration was 186.19 minutes (95 % CI : 109.09 to 263.29); statistical analysis revealed a high level of significance, with a Z -value of 4.73 and a p -value of < 0.00001 (Fig. 5). Overall, seven studies [2, 3, 21, 23, 35, 39] reported that the addition of dexmedetomidine significantly decreased postoperative analgesic requirement at12 to 24 hours or more in comparison to control. The amount of postoperative analgesic drug consumed during 24h of following by the patients exposed to dexmedetomidine combined with local anesthesia was significantly less than standard local anesthesia with P < 0.05 [2, 23, 35]. Duration of postoperative analgesia was determined by measuring the time from the end of the procedure until the patient's pain score reached a predefined threshold (e.g., VAS ≥ 3) or they requested rescue analgesia [21, 23]. Patients were commonly prescribed a combination of analgesics, including Paracetamol, Diclofenac Potassium, Enzoflam, Ketorolac Tromethamine, and pethidine, for pain relief [2, 21, 23, 39]. The studies also documented the use of rescue analgesics, typically intravenous Tramadol, for breakthrough pain when the VAS score was ≥ 4 [2, 23]. Because of the different analgesics used and the lack of sufficient reporting to allow for pooling, we could not estimate the effect of this outcome. Post-operative Pain Management and Follow-up The included studies emphasised the importance of postoperative pain management and follow-up in dental procedures, particularly third molar extractions, which are known to induce moderate to severe pain [21, 35]. Varied pain scores and follow-up protocols were used within the first 12 to 24 hours after surgery to evaluate the efficacy of various anaesthetic procedures. The Visual Analogue Scale ( VAS ) was widely employed in seven included investigations [2, 3, 23, 24, 35, 38, 39], requiring patients to mark their pain level on a 10-centimetre line ranging from 10 (worst agony possible) to 0 (no pain). However, just one study used the Faces Pain Scale (FPS) [21], which depicts varying levels of pain through a sequence of facial emotions ranging from smiling to crying (Table 2 ). Pain intensity was measured regularly after the surgery to improve patient comfort and check analgesia effectiveness. The studies assessed pain at various time intervals following surgery, including 1, 3, 6, and 12 hours [21, 35, 38]. This enabled researchers to monitor the progression of pain alleviation and identify potential rebound pain. Table 2 Individual study data for postoperative pain comparing dexmedetomidine and control at 12–24-hours follow-up. Study ID Dexmedetomidine Control P Value Pain Scoring System Used Main (SD) Main (SD) Bhardwaj et al ,2024 [38] 2 5 p < 0.05 Visual Analog Scale (VAS), postoperative pain score at 12 h Doshi et al, 2024 [21] 7.22 (0.56) h† 4.54 (0.38) h† 2.1 (0.38) h†* p = 0.0001 Face Pain Scale (FPS), pain score reached a level of 3 or higher, the time was recorded, (†or † *) Another 2 groups Patil et al, 2022 [35] 1 4 P = 0.0001 Visual Analog Scale (VAS), postoperative pain score at 24 hours, Estimated from figure Suryawanshi et al, 2022 [23] 443.60 99.28) min 332.50 (73.20) min‡ p = 0.000 Visual Analog Scale (VAS), ‡The time recorded from the point of completion of the extraction (In maxillary) to the time when the pain intensity was scored ≥ 3 Suryawanshi et al, 2022 [23] 446.12 (86.32) min ‡ 335.13 (69.82) min ‡ p = 0.000 Visual Analog Scale (VAS), ‡The time recorded from the point of completion of the extraction (In mandibular) to the time when the pain intensity was scored ≥ 3 Elsawy et al, 2021[2] 2 (2,3) * 3 (3,3) * p < 0.05 Visual Analog Scale (VAS) pain score during 24 hours of follow up, *Interquartile range Priyaranjan et al, 2020 [3] 3 4 p < 0.05 Visual Analog Scale (VAS) pain score Singh et al, 2017 [24] Not specified Not specified Not specified Visual Analog Scale (VAS) Alizargar et al, 2021[39] 1.60 (2.37) 4.00 (2.49) p = 0.003 Visual Analog Scale (VAS), postoperative pain score at 24 hours Sedation Effect A few studies specifically investigated the sedation side effects of dexmedetomidine when used as an adjunct to local anesthesia. For instance, Etemadi et al. found that patients receiving dexmedetomidine during third molar surgery felt significantly more relaxed than those in the control group[13]. Ouchi and Sugiyama found that increasing concentrations of dexmedetomidine led to an increase in sedation scores [36]. However, it is essential to keep in mind that no participant in any of the studies reported experiencing profound sedation. The remaining studies acknowledged the positive properties of dexmedetomidine as part of its mechanism of action but did not focus on this aspect as a primary outcome [19, 22]. Haemodynamic Event Most of the involved studies found no significant changes in heart rate, systolic blood pressure, diastolic blood pressure, or oxygen saturation when comparing a local anesthetic combined with dexmedetomidine to a local anesthetic alone or a local anesthetic with adrenaline [2, 3, 19–24, 35–37]. While several studies noted a drop in either heart rate or blood pressure in the dexmedetomidine group, these usually were slight and did not lead to hypotension or bradycardia [3, 4, 19, 20]. One study even noted that oxygen saturation was greater in the dexmedetomidine group [19]. Regarding the meta-analysis of Intraoperative heart rate(30 minutes), among seven studies (350 patients) [21, 23, 24, 35, 38–40], the mean difference was 0.10 bpm (95% CI : -1.02 to 1.23), indicating no significant impact ( p = 0.86). Heterogeneity was low ( I² = 12 % ). Heart rate at 120 minutes, from three studies (150 patients) [21, 35, 40], the mean difference was 0.00 bpm (95 % CI : -1.20 to 1.20), also showing no significant effect impact ( p = 1.00). With no heterogeneity ( I² = 0%). While heart rate at postoperative, from four studies (200 patients) [23, 24, 38, 39], the mean difference was 1.72 bpm (95% CI : -1.59 to 4.02), also showing no significant effect impact ( p = 0.14), With low heterogeneity ( I² = 20%) (Fig. 6 ). The meta-analysis evaluated the effect of dexmedetomidine on systolic blood pressure intraoperatively (30 min), 120 minutes, and postoperatively. Intraoperative systolic pressure, among seven studies (350 patients) ) [21, 23, 24, 35, 38–40], the mean difference was − 0.13 mmHg (95% CI : -1.53 to 1.80), showing no significant impact ( p = 0.88) with no heterogeneity ( I² = 0 % ). Subgroup analysis of Systolic pressure at 120 minutes for three studies (150 patients) ) [21, 35, 40], the mean difference was − 1.65 mmHg (95% CI : -0.68 to 3.98), also indicating no significant effect ( p = 0.16) and no heterogeneity ( I² = 0%). Whereas, postoperatively systolic blood pressure, from four studies (200 patients) [23, 24, 38, 39], the mean difference was − 2.15 bpm (95% CI : -4.64 to 0.34), showing no significant effect impact ( p = 0.09) with low heterogeneity ( I² = 49 % ) (Fig. 7 ). Our meta-analysis also clarified the impact of dexmedetomidine on diastolic blood pressure during surgery (30 minutes), 120 minutes, and postoperatively. Intraoperative Diastolic Pressure, across seven studies (350 patients) ) [21, 23, 24, 35, 38–40], the mean difference was − 0.13 mmHg (95% CI : -1.53 to 1.80), with no significant effect ( p = 0.88) with no heterogeneity ( I² = 0 % ). Diastolic pressure at 120 minutes, among three studies (150 patients) ) [21, 35, 40], the mean difference was 1.65 mmHg (95 % CI : -0.68 to 3.98), again showing no significant impact ( p = 0.16) and no heterogeneity ( I² = 0%). In addition, in four studies (200 patients) at postoperative [23, 24, 38, 39], the mean difference was − 2.15 mmHg (95% CI : -4.64 to 0.34), again showing no significant impact ( p = 0.09) and low heterogeneity ( I² = 49%) (Fig. 8). Furthermore, the oxygen saturation meta-analysis also performed with five studies included [23, 24, 35, 38, 39], the mean difference was − 0.00 SpO 2 (95 % CI : -0.11 to 0.10), with no significant effect ( p = 0.94) with no heterogeneity ( I² = 0%) (Fig. 9 ). Figure 6 Mean heart rate risk difference with 95% confidence interval in dexmedetomidine patients versus control. Figure 7 Mean systolic blood pressure risk difference with 95% confidence interval for dexmedetomidine versus control patients. Figure 8 Mean diastolic blood pressure risk difference with 95% confidence interval for dexmedetomidine versus control patients. Figure 9 Mean diastolic oxygen saturation risk difference with 95% confidence interval for dexmedetomidine versus control patients. Discussion Our systematic review and meta-analysis support that dexmedetomidine can be used with dental local anaesthesia as an effective adjuvant, significantly shortening the onset time by an average of 48.78 seconds, making the anaesthesia more effective. Furthermore, it extended the duration of anaesthesia by an average of 31.10 minutes, which is good for prolonged surgeries, and improved patient comfort by possibly decreasing the number of additional injections. These findings agreed with other systematic reviews and meta-analyses describing dexmedetomidine's efficacy in many clinical practices. For instance, Hussain et al. investigated dexmedetomidine, which significantly increased both the onset and duration of sensory and motor block durations in brachial plexus blocks [16]. Specifically, they observed a reduction in sensory block onset time by 3.19 minutes and a prolongation of sensory block duration by 261.41 minutes12. Similarly, motor block onset was reduced by 2.92 minutes, with duration prolonged by 200.9 minutes [16]. Further supporting the finding regarding the extended duration of anaesthesia with dexmedetomidine, Abdallah et al., in their systematic review and meta-analysis, found that dexmedetomidine used in neuraxial and peripheral nerve blocks, prolonged sensory block duration by 150 minutes with intrathecal administration [12]. Another study focusing on dexmedetomidine as an adjunct to local anaesthetics in an erector spinae plane block (ESPB) observed a prolonged duration of anaesthesia and reduced postoperative analgesic demand [17]. The studies mentioned above, and others focusing on upper extremity nerve blocks consistently demonstrate dexmedetomidine's benefits in enhancing onset times across different procedural contexts [5]. This finding suggests that dexmedetomidine as an adjuvant to local anaesthesia had potential benefits that extend beyond dental procedures to various clinical settings. In terms of postoperative pain management, our meta-analysis showed a significantly prolonged duration of analgesia, with a mean of 186.19 minutes and reduced postoperative analgesic demands with dexmedetomidine. This also concurs with other studies in different clinical scenarios. For example, Wu et al., in their meta-analysis on neuraxial applications of dexmedetomidine, reported significantly enhanced analgesic duration [41]. Similarly, a study by Zhao et al. on femoral nerve blocks further confirmed that dexmedetomidine augmented postoperative pain control [11]. Our studies also reported that from the safety perspective, no serious adverse changes in heart rate, blood pressure, and oxygen saturation were related to dexmedetomidine. The minor fluctuations in heart rate or blood pressure occasionally did not progress to clinically significant hypotension or bradycardia, consistent with other meta-analyses where transient, easily managed bradycardia was noted [11, 16]. The low incidence of postoperative adverse events in dentistry in the current review compared to other systematic reviews and meta-analyses reporting some hypotension or bradycardia may be explained by the low dose of dexmedetomidine used in most of our included studies, 1 µg/ml . This suggests that dexmedetomidine is safe and effective for managing dental postoperative pain, especially in low dosages. Considering these positive outputs, we need to point out some limitations that must be considered in our study. A high degree of heterogeneity was demonstrated, suggesting variability in methodological differences, variations in the type of anaesthetic agents used, and differences in the demographics of the patients included. This heterogeneity complicates the pooling of data, especially regarding the consumption of postoperative analgesics, as inconsistent reporting across studies impedes a detailed assessment regarding the role of dexmedetomidine for pain management. That would then require future studies to standardise methodologies and report trials to integrate data better. It would also be interesting to study the effect of different doses and long-term effects of dexmedetomidine in a wide range of patients to establish further the drug's utility and safety in dental anaesthesia. Conclusion In general, this study has provided evidence for the benefits of dexmedetomidine as an adjunct to local anaesthesia in dentistry. As an adjuvant, dexmedetomidine can exhibit multiple advantages with low dosage, including faster onset and prolonged duration of anaesthesia, better postoperative pain control, and a good safety profile. Some heterogeneity in specific analyses and limitations in data availability are needed for further research. Declarations Ethics Approval and Consent to Participate Not applicable. Consent for Publication All authors have given consent for publication. Availability of Data and Material The original data presented in this article are available upon reasonable request from the corresponding author. Competing Interests There is no competing interest to declare. Funding No external funding was received for this study. Authors’ Contribution SAA, WAA, TW, and NL contributed to the conceptualization and study design. SAA and WAA collected and extracted the data. SAA, WAA, and NL performed data analysis and interpretation. All authors SAA, WAA, NL, TW, WW, MW, and YQH were involved in the writing or revision of the manuscript and approved the final version. Acknowledgements Not applicable. Authors’ Information Not applicable. 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Wang, Effects of dexmedetomidine as a perineural adjuvant for femoral nerve block: A systematic review and meta-analysis. Plos One, 2020. 15 (10) DOI: https://doi.org/10.1371/journal.pone.0240561. Abdallah, F. and R. Brull, Facilitatory effects of perineural dexmedetomidine on neuraxial and peripheral nerve block: a systematic review and meta-analysis. British journal of anaesthesia, 2013. 110 (6): p. 915-925 DOI: https://doi.org/10.1093/bja/aet066. Etemadi Sh, M., et al., Effect of Dexmedetomidine Added to Lidocaine Cartridge on the Level of Patient Sedation, Cooperation, and Patient and Surgeon Satisfaction during Mandibular Third-Molar Extraction Surgery: A Randomized Double-Blind Controlled Trial. International Journal of Dentistry, 2022. 2022 DOI: https://doi.org/10.1155/2022/4722674. Vahedi, Z., A. Moshari, and M. Moshari, Efficacy of adding dexmedetomidine to lidocaine to enhance inferior alveolar nerve block in patients with asymptomatic irreversible pulpitis: double-blind randomized clinical trial. Clinical Oral Investigations, 2022. 26 (7): p. 4727-4734 DOI: https://doi.org/10.1007/s00784-022-04436-7. Alsultan, D., Efficacy of dexmedetomidine as an adjuvant in transverse abdominal plane blocks for cesarean section pain management: A systematic review and meta-analysis. Saudi Journal of Anaesthesia, 2024. 18 (4): p. 545-555 DOI: https://doi.org/10.4103/sja.sja_306_24. Hussain, N., et al., Investigating the Efficacy of Dexmedetomidine as an Adjuvant to Local Anesthesia in Brachial Plexus Block: A Systematic Review and Meta-Analysis of 18 Randomized Controlled Trials. Reg Anesth Pain Med, 2017. 42 (2): p. 184-196 DOI: https://doi.org/10.1097/aap.0000000000000564. Liang, Y., S. Xiaojuan, and L. He, The effect and safety of dexmedetomidine as an adjuvant to local anesthetics in erector spinae plane block: a systematic review and meta-analysis of randomized controlled trials. 2023 DOI: https://doi.org/10.1186/s12871-023-02019-x. Albrecht, E., et al., Dexamethasone Is Superior to Dexmedetomidine as a Perineural Adjunct for Supraclavicular Brachial Plexus Block: Systematic Review and Indirect Meta-analysis. Anesth Analg, 2019. 128 (3): p. 543-554 DOI: https://doi.org/10.1213/ANE.0000000000003860. Nalawade, S., et al., A clinical comparative study of dexmedetomidine as an adjuvant to 2% plain lignocaine and 2% lignocaine with 1: 200,000 adrenaline as local anesthetic agents for surgical removal of impacted mandibular third molars. Natl. j. maxillofac. surg., 2021. 12 (2): p. 255-261 DOI: https://doi.org/10.4103/njms.NJMS_7_20. Ouchi, K., Dexmedetomidine 2 ppm Is Appropriate for the Enhancement Effect of Local Anesthetic Action of Lidocaine in Inferior Alveolar Nerve Block: a Preliminary, Randomized Cross-over Study. Clinical journal of pain, 2020. 36 (8): p. 618‐625 DOI: https://doi.org/10.1097/AJP.0000000000000839. Doshi, A., N. Bhola, and A. Agarwal, Comparing the efficacy of adrenaline, clonidine, and dexmedetomidine in enhancing local anesthesia for impacted third molar extraction: a randomized controlled trial. Journal of dental anesthesia and pain medicine, 2024. 24 (4): p. 285‐295 DOI: https://doi.org/10.17245/jdapm.2024.24.4.285. Khandaitkar, S., et al., A clinical study to determine the efficacy of 7ppm dexmedetomidine as an adjuvant to 2% lignocaine in infraorbital nerve block. The British journal of oral & maxillofacial surgery, 2016. 54 (9): p. 997-1000 DOI: https://dx.doi.org/10.1016/j.bjoms.2016.07.011. Suryawanshi, T., et al., Comparative Analysis of Anaesthetic Efficacy of 2% Lignocaine With Dexmedetomidine as an Adjunct in Nerve Blocks for Dental Extractions: A Randomised Controlled Study. Cureus, 2022. 14 (9) DOI: https://doi.org/10.7759/cureus.28867. Singh, V., et al., Dexmedetomidine as an Additive to Local Anesthesia: A Step to Development in Dentistry. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons, 2018. 76 (10): p. 2091.e1-2091.e7 DOI: https://dx.doi.org/10.1016/j.joms.2018.05.037. Ryu, D.-S., et al., Sedation protocol using dexmedetomidine for third molar extraction. Journal of Oral and Maxillofacial Surgery, 2016. 74 (5): p. 926. e1-926. e7 DOI: https://doi.org/10.1016/j.joms.2015.12.021. Page, M.J., et al., The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Systematic Reviews, 2021. 10 (1): p. 89 DOI: https://doi.org/10.1186/s13643-021-01626-4. Sterne, J.A.C., et al., RoB 2: a revised tool for assessing risk of bias in randomised trials. Bmj, 2019. 366 : p. l4898 DOI: https://doi.org/10.1136/bmj.l4898. Igelström, E., et al., Cochrane's risk of bias tool for non-randomized studies (ROBINS-I) is frequently misapplied: A methodological systematic review. J Clin Epidemiol, 2021. 140 : p. 22-32 DOI: https://doi.org/10.1016/j.jclinepi.2021.08.022. Mansour, R.F. and M.S. Abdelghany, Ultrasound-guided suprazygomatic maxillary nerve block in cleft palate surgery: The efficacy of adding dexmedetomidine to bupivacaine. Egyptian Journal of Anaesthesia, 2021. 37 (1): p. 329-336 DOI: https://doi.org/10.1080/11101849.2021.1953832. Mostafa, M.F., et al., Dexmedetomidine during suprazygomatic maxillary nerve block for pediatric cleft palate repair, randomized double-blind controlled study. Korean Journal of Pain, 2020. 33 (1): p. 81-89 DOI: https://doi.org/10.3344/kjp.2020.33.1.81. Alansary, A.M., M.M. Ali, and M.A. Elshafie, A randomized controlled trial of dexmedetomidine vs magnesium sulfate as adjuvants to bupivacaine in infraorbital nerve block for perioperative analgesia in pediatric patients undergoing cleft lip surgery. Anaesthesia Pain & Intensive Care, 2023. 27 (4): p. 514-522 DOI: https://doi.org/10.35975/apic.v27i4.2261. El-Emam, E.-S. and E. El motlb, Comparative Evaluation of Dexamethasone and Dexmedetomidine as Adjuvants for Bupivacaine in Ultrasound-Guided Infraorbital Nerve Block for Cleft Lip Repair: A Prospective, Randomized, Double-Blind Study. Anesth Essays Res, 2019. 13 (2): p. 354-358 DOI: https://doi.org/10.4103/aer.AER_14_19. Stepien, A., P. Stepien, and J. Kornatowska, DEXMEDETOMIDINE AS AN ADDITIVE TO LOCAL ANESTHESIA IN DENTISTRY. Prospects in Pharmaceutical Sciences, 2024. 22 (3): p. 58-61 DOI: https://doi.org/10.56782/pps.211. Tonooka, Y. and K. Sunada, Dexmedetomidine Enhances the Pulpal Anesthetic Effect of Lidocaine: A Pilot Study. Anesthesia progress, 2018. 65 (1): p. 38-43 DOI: https://doi.org/10.2344/anpr-65-01-05. Patil, S.M., et al., Does dexmedetomidine combined with levobupivacaine in inferior alveolar nerve blocks among patients undergoing impacted third molar surgery control postoperative morbidity? Journal of dental anesthesia and pain medicine, 2022. 22 (2): p. 145‐153 DOI: https://doi.org/10.17245/jdapm.2022.22.2.145. Ouchi, K. and K. Sugiyama, Dexmedetomidine Dose Dependently Enhances the Local Anesthetic Action of Lidocaine in Inferior Alveolar Nerve Block: a Randomized Double-Blind Study. Regional anesthesia and pain medicine, 2016. 41 (3): p. 348‐355 DOI: https://doi.org/10.1097/AAP.0000000000000380. Kosar, S., et al. Use of Dexmedetomidine in Dentistry as an Additive to Local Anesthesia in Place of Adrenaline . 2021. DOI: https://doi.org/10.21275/ART20205 Bhardwaj, S., et al., Ropivacaine vs. Ropivacaine-Dexmedetomidine for IANB in Mandibular Third Molar Extraction. Nanotechnology Perceptions, 2024: p. 948-955 DOI: https://doi.org/10.62441/nano-ntp.v20iS9.69. Alizargar, J., et al., Injection of Lidocaine Alone versus Lidocaine plus Dexmedetomidine in Impacted Third Molar Extraction Surgery, a Double-Blind Randomized Control Trial for Postoperative Pain Evaluation. Pain research & management, 2021. 2021 : p. 6623792 DOI: https://dx.doi.org/10.1155/2021/6623792. Yamane, A., et al., Effect of dexmedetomidine injected into the oral mucosa in combination with lidocaine on local anesthetic potency in humans: a crossover double-blind study. J Oral Maxillofac Surg, 2015. 73 (4): p. 616-21 DOI: https://doi.org/10.1016/j.joms.2014.09.029. Wu, H.-H., et al., Does dexmedetomidine as a neuraxial adjuvant facilitate better anesthesia and analgesia? A systematic review and meta-analysis. PloS one, 2014. 9 (3): p. e93114 DOI: https://doi.org/10.1371/journal.pone.0093114. Tables Table 1 is available in the Supplementary Files section. Supplementary Files Table1.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 07 Aug, 2025 Reviewers agreed at journal 06 Jan, 2025 Reviewers invited by journal 03 Jan, 2025 Editor assigned by journal 03 Jan, 2025 First submitted to journal 06 Dec, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5597524","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":397259992,"identity":"2627a9e4-cf50-4b7f-9af9-bc0e064ba18b","order_by":0,"name":"Salah Ameen Abdu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIiWNgGAWjYFAC5gZmBjYw4wCQkJAhQgsjRAsPG1sCSAsPKVp4DEBcwlrk2w82fi4os8mzl+/5/OpGjQUPA/vhoxvwaTE4k9gsPeNcWjEPG+8265xjQIfxpKXdwKuFIbFBmrftcGIPUItxDhtQiwSPGV4t8v0Pm3/ztv0HauF5ZpzzjwgtDDcS24C2HABpYX6c20aEFoMbD9usec4lJ/YcSzNjzu2TAIYcAb/I9ycfvs1TZpfY3nz48eecb3Vy/OyHj+F3GBJgkwCTxCoHAeYPpKgeBaNgFIyCkQMAKhJD+WWcgEwAAAAASUVORK5CYII=","orcid":"https://orcid.org/0009-0004-0846-9847","institution":"Central South University First Hospital: Xiangya Hospital Central South University","correspondingAuthor":true,"prefix":"","firstName":"Salah","middleName":"Ameen","lastName":"Abdu","suffix":""},{"id":397259993,"identity":"b2705f02-6a0b-449a-ba74-69ce7b92c0e5","order_by":1,"name":"Wafa Ali Asaad","email":"","orcid":"","institution":"Kunming Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wafa","middleName":"Ali","lastName":"Asaad","suffix":""},{"id":397259994,"identity":"ce91b3b0-334f-413d-be31-4ca886cd1817","order_by":2,"name":"Tao Wei","email":"","orcid":"","institution":"Kunming Medical University","correspondingAuthor":false,"prefix":"","firstName":"Tao","middleName":"","lastName":"Wei","suffix":""},{"id":397259995,"identity":"0e5b04ab-cc63-454c-9565-23baf69f43d5","order_by":3,"name":"Muaadh Wdaan","email":"","orcid":"","institution":"Central South University First Hospital: Xiangya Hospital Central South University","correspondingAuthor":false,"prefix":"","firstName":"Muaadh","middleName":"","lastName":"Wdaan","suffix":""},{"id":397259996,"identity":"f48a45de-af90-4e9d-ad29-c836329780c4","order_by":4,"name":"Wendong Wan","email":"","orcid":"","institution":"Central South University First Hospital: Xiangya Hospital Central South University","correspondingAuthor":false,"prefix":"","firstName":"Wendong","middleName":"","lastName":"Wan","suffix":""},{"id":397259997,"identity":"42be9137-a8d8-4783-97d4-9e86b07701d1","order_by":5,"name":"Yu-Qi Huang","email":"","orcid":"","institution":"Central South University First Hospital: Xiangya Hospital Central South University","correspondingAuthor":false,"prefix":"","firstName":"Yu-Qi","middleName":"","lastName":"Huang","suffix":""},{"id":397259998,"identity":"32fe862e-72d3-4f6a-b97b-7bc59732753f","order_by":6,"name":"Ning Li","email":"","orcid":"","institution":"Central South University First Hospital: Xiangya Hospital Central South University","correspondingAuthor":false,"prefix":"","firstName":"Ning","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2024-12-07 07:21:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5597524/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5597524/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":75995516,"identity":"c239dbef-9b5c-486e-a41c-ca37fb5d5aa8","added_by":"auto","created_at":"2025-02-11 09:51:43","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":14499,"visible":true,"origin":"","legend":"\u003cp\u003eDiagram illustrates the complete process of study inclusion.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5597524/v1/dd78f2ab4ecdf093c4860641.png"},{"id":75993428,"identity":"7df42909-1115-477d-847d-8341dc6d7276","added_by":"auto","created_at":"2025-02-11 09:35:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":93536,"visible":true,"origin":"","legend":"\u003cp\u003ea Assessment of bias for all randomized trials included in in this study.\u003c/p\u003e\n\u003cp\u003eb Assessment of bias for both nonrandomized trials included in this study.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5597524/v1/efc06fcb6a077e00d11b4f40.png"},{"id":75994879,"identity":"144ba337-faaf-465f-8f6c-1519adf51964","added_by":"auto","created_at":"2025-02-11 09:43:43","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":151768,"visible":true,"origin":"","legend":"\u003cp\u003ea. Mean onset time for nerve blockade in seconds with 95% CI for dexmedetomidine versus control.\u003c/p\u003e\n\u003cp\u003eb Subgroup mean onset time for maxillary and mandibular nerve blockade with 95% CI for dexmedetomidine.\u003c/p\u003e\n\u003cp\u003ec Subgroup mean onset time for nerve blockade in seconds with 95% CI for dexmedetomidine \u003cem\u003e1µg/ml.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ed Subgroup mean onset time for nerve blockade in seconds with 95% CI for dexmedetomidine compared to lidocaine.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5597524/v1/40091fc05f0ef6d5747c9103.png"},{"id":75993426,"identity":"cf5f5016-939b-4627-bee9-6eeabda2a2ff","added_by":"auto","created_at":"2025-02-11 09:35:43","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":15609,"visible":true,"origin":"","legend":"\u003cp\u003eMean duration of nerve blockade in minutes with 95% CI for dexmedetomidine versus control patients.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-5597524/v1/7113cfe1ff2b9dbb6c6eccaf.png"},{"id":75997121,"identity":"81b66dbf-2df8-4a38-847e-3c3c2f989a44","added_by":"auto","created_at":"2025-02-11 09:59:43","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":11469,"visible":true,"origin":"","legend":"\u003cp\u003eMean duration of postoperative analgesia in minutes with 95% CI for dexmedetomidine versus control patients.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-5597524/v1/258929cf0fb75376d8487ea8.png"},{"id":75994881,"identity":"351eb888-927e-4fba-8235-b09eaa497cab","added_by":"auto","created_at":"2025-02-11 09:43:44","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":28612,"visible":true,"origin":"","legend":"\u003cp\u003eMean heart rate risk difference with 95% confidence interval in dexmedetomidine patients versus control.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-5597524/v1/90e5f2f13dbf0cda2a882f76.png"},{"id":75994874,"identity":"0591ed7a-b81c-48ae-ada9-5996a3e6cb21","added_by":"auto","created_at":"2025-02-11 09:43:43","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":29393,"visible":true,"origin":"","legend":"\u003cp\u003eMean systolic blood pressure risk difference with 95% confidence interval for dexmedetomidine versus control patients.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-5597524/v1/8132686fe8a5e3e79f20af66.png"},{"id":75993454,"identity":"f706aeb2-96f1-42cc-8e4b-8353a602bfc8","added_by":"auto","created_at":"2025-02-11 09:35:44","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":29173,"visible":true,"origin":"","legend":"\u003cp\u003eMean diastolic blood pressure risk difference with 95% confidence interval for dexmedetomidine versus control patients.\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-5597524/v1/430c6537c232b2fac4ad1113.png"},{"id":75994920,"identity":"e9299138-c488-455d-9a82-2fa916e40322","added_by":"auto","created_at":"2025-02-11 09:43:47","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":9243,"visible":true,"origin":"","legend":"\u003cp\u003eMean diastolic oxygen saturation risk difference with 95% confidence interval for dexmedetomidine versus control patients.\u003c/p\u003e","description":"","filename":"9.png","url":"https://assets-eu.researchsquare.com/files/rs-5597524/v1/bca89b1c7111d1260ce54870.png"},{"id":76674789,"identity":"4340d123-e708-479a-a0ac-1cd703874a3f","added_by":"auto","created_at":"2025-02-19 14:14:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1183431,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5597524/v1/3d6b09ab-f5c2-4f68-a0e9-a9a2d9ade725.pdf"},{"id":75993435,"identity":"14d040e5-e850-4928-ac62-5318264aab7a","added_by":"auto","created_at":"2025-02-11 09:35:43","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":12241,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5597524/v1/1f25c2b719d5abc8b85d1ecd.xlsx"}],"financialInterests":"","formattedTitle":"Investigating the Efficacy of Dexmedetomidine as an Adjuvant to Local Anesthesia in Dentistry: Systematic Review and Meta Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEffective postoperative pain control is an integral part of patient care in dentistry, especially for procedures such as third molar extractions, which are known to be significantly painful postoperatively [1\u0026ndash;3]. Local anaesthesia forms the main modality of pain management in dental surgery; however, it suffers from drawbacks related to a very limited duration of action and systemic toxicity with larger doses of local anaesthetics [4]. Consequently, the search for adjuvants that enhance the quality and duration of anesthesia and analgesia with a reduction of adverse effects has been continued [4].\u003c/p\u003e \u003cp\u003eDexmedetomidine (DEX) is an α2-adrenergic receptor agonist that has demonstrated high selectivity and appeared as an effective adjuvant to extend the action of local anesthetics [5\u0026ndash;10]. DEX possesses analgesic, anxiolytic, and sedative effects with minimal respiratory depression [5\u0026ndash;7, 9, 11\u0026ndash;14]. When used with local anesthetics, DEX can prolong analgesia duration, reduce postoperative pain scores, and reduce the need for rescue analgesics [5\u0026ndash;12, 15, 16]. The application of DEX as an adjuvant with local anaesthesia has become a subject of interest in dentistry; however, there is still a need for an overview regarding efficacy and the profile of this drug's safety. Numerous systematic reviews and meta-analyses were performed to outline the role of DEX in regional anesthesia techniques, such as peripheral nerve blocks, neuraxial blocks, and intravenous regional anesthesia [5\u0026ndash;8, 10, 11, 17, 18]. However, there is limited conclusive evidence regarding its application in dentistry, and the optimal dosage for dental purposes is not clearly specified [5, 6, 10, 15, 19, 20]. Furthermore, while generally considered safe, DEX can cause haemodynamic changes, such as bradycardia and hypotension [3, 12, 15, 16]. The potential effect of DEX in modifying the parameters of haemodynamics becomes relevant in dental settings, where the majority of procedures are day-care surgeries and demand quick recovery with minimal side effects [3, 9]. Although several studies have explored the hemodynamic effects of DEX as an adjuvant to local anaesthesia in dentistry, the results were conflicting [3, 4, 9, 13, 19\u0026ndash;25]. Therefore, the primary objective of our systematic review and meta-analysis is to assess whether dexmedetomidine prolongs the duration of dental nerve blockade as an adjuvant to local anesthesia compared with the use of local anesthesia alone (control) in adult patients\u0026thinsp;\u0026ge;\u0026thinsp;10 years of age undergoing dental procedures. We further want to elaborate on the adverse events profile of dexmedetomidine in order to understand its safety.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e The PRISMA methodological approach was adopted in the present study to systematically conduct the review and meta-analysis. It, therefore, provided a systematic guide on the identification, evaluation, and synthesis of studies in a manner that made the review as transparent and reproducible as possible. In line with the PRISMA guidelines, we set out to provide a comprehensive overview of the available evidence with respect to the effectiveness and safety of dexmedetomidine as an adjunct to local dental anesthesia [26].\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCriteria for Study Inclusion and Exclusion\u003c/h2\u003e \u003cp\u003e Our systematic review and meta-analysis focused on clinical trials that evaluated dexmedetomidine as an adjunct to local anaesthesia in adults (\u0026ge;\u0026thinsp;10 years) undergoing oral procedures. Only studies using local anaesthesia were included to maintain consistency and minimise the high level of expected heterogeneity. The choice of local anaesthetic and its dosage and the specific dose of dexmedetomidine were not considered for inclusion. The articles published in English are included in this systematic review and meta-analysis. Studies primarily investigating dexmedetomidine's effect on dental pulpal anaesthesia were excluded.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eIdentification of Relevant Studies\u003c/h3\u003e\n\u003cp\u003eAn experienced evidence-based medicine librarian (TW) developed a comprehensive search strategy, including both published and unpublished studies, across multiple databases: MEDLINE, EMBASE, Cochrane Library, Ovid, Web of Science and Google Scholar. The title of each search result after January 2014 to November 4, 2024, was meticulously screened by two independent reviewers, SAA and WAA. First of all, screening was done in duplicate based on title and abstract. Following that, all the potentially qualified articles would undergo a full-text review to confirm their eligibility for inclusion. During this time, any discrepancies arising between these three reviewers were resolved through collaboration by discussion to a consensus. In case there was no consensus through discussion, an independent third reviewer's (NL) evaluation provided an assessment of the disagreement. Lastly, the bibliographies and citations of all the included articles were carefully scanned to ensure the comprehensiveness of the search strategy regarding any missed studies.\u003c/p\u003e\n\u003ch3\u003eOutcomes Assessed\u003c/h3\u003e\n\u003cp\u003eThe primary outcomes of our meta-analysis were to compare the onset and duration of dental local nerve blockade with the addition of dexmedetomidine versus control. The secondary outcomes of this review were overall postoperative pain at 12\u0026ndash;24-hour follow-up, duration of analgesia, postoperative analgesic consumption, and adverse events. The adverse events included in this meta-analysis were hypotension (systolic and diastolic blood pressure), oxygen saturation, and heart rate. These were selected because they were commonly reported by involved studies and were considered to be clinically important.\u003c/p\u003e\n\u003ch3\u003eData Management and Extraction\u003c/h3\u003e\n\u003cp\u003eA data extraction form was designed and then piloted by an independent reviewer (SAA). The data extraction form collected information regarding the clinical setting, demographics, outcome data (eg, onset of anesthesia, duration of anesthesia), and adverse events. Two independent reviewers (SAA, WAA) extracted data to ensure accuracy and minimize risk of error. In the case of a disagreement in data extraction, the 2 reviewers discussed until a consensus was reached. If a consensus still could not be reached, a third reviewer (NL) was tasked with making the final decision. The study characteristic\u003c/p\u003e\n\u003ch3\u003eMethodological Quality Assessment Process\u003c/h3\u003e\n\u003cp\u003eTwo independent reviewers (Salah and Wafa) conducted the methodological quality assessment of the included studies. The Revised Cochrane Risk-of-Bias tool (RoB 2) was used to evaluate the 14 randomized controlled trials across five domains, with risk levels categorized as high (red), unclear (yellow), or low (green) [27]. The ROBINS-I tool assessed the 2 non-randomized studies across seven domains, with risk levels designated as serious (dark red), critical/high (red), moderate (yellow), or low (green) [28]. An unweighted kappa statistic was calculated to evaluate initial interrater agreement. Disagreements between reviewers were resolved through discussion, and when consensus couldn't be reached, a third reviewer (TW) was consulted for final decision-making.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eMeta-Analysis and Heterogeneity Assessment\u003c/h2\u003e \u003cp\u003eThis meta-analysis was carried out using Review-Manager software provided by the Cochrane Collaboration (RevMan V.5.1). Binary outcome data were pooled and expressed as risk ratios (\u003cem\u003eRR\u003c/em\u003e) with confidence intervals (\u003cem\u003eCI\u003c/em\u003e) of 95%. Continuous outcome data were pooled using mean difference (MD) with confidence intervals (\u003cem\u003eCI\u003c/em\u003e) of 95\u003cem\u003e%\u003c/em\u003e. The \u003cem\u003eChi-\u003c/em\u003esquare test was used with the Mantel-Haenszel method (\u003cem\u003eI\u003c/em\u003e2\u0026thinsp;\u0026ge;\u0026thinsp;50\u003cem\u003e%\u003c/em\u003e, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.1) to determine the heterogeneity of the included studies. Looking for possible reasons for heterogeneity, subgroup and sensitivity analyses were performed. A random-effects model (DerSimonian and Laird method) was adopted when statistical or clinical heterogeneity was assessed as high, considering the variability among studies. A \u003cem\u003eP\u003c/em\u003e value of \u0026le;\u0026thinsp;0.05 was established as the significance level for reporting the overall effect size. With a low heterogeneity, a fixed-effects model was used to evaluate the assumed common underlying treatment.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStudy Characteristics\u003c/h2\u003e \u003cp\u003eAt first, a literature search identified a total of 1220 articles. Ninety-seven articles were assessed as a primary result for initial screening. After screening the title and abstract, 23 articles were assessed for full-text eligibility. Of these articles, 16 articles were included in this meta-analysis, seven articles were excluded because of their age\u0026thinsp;\u0026lt;\u0026thinsp;10 [29\u0026ndash;32], article review [33], and dental pulp studies[14, 34]. The full-flow diagram of study inclusion is shown in (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). A comprehensive overview of all included studies is presented in Table\u0026nbsp;1. All studies were published between 2014 and 2024. Across all included studies, 658 patients (877 samples) were assessed. Regarding the technique of local anesthetic used, a total of 15 studies utilized nerve block [2\u0026ndash;4, 13, 19\u0026ndash;24, 35\u0026ndash;39], 11 mainly used an inferior alveolar [2, 3, 13, 19\u0026ndash;22, 35, 36, 38, 39], while 4 study used infraorbital nerve block and inferior alveolar nerve block [4, 23, 24, 37]. Dexmedetomidine was used as an adjuvant to three different local anesthetics, which included lidocaine [2\u0026ndash;4, 13, 19\u0026ndash;24, 36, 37, 39, 40], levobupivacaine [35], ropivacaine [38]. Across the studies, the dose of dexmedetomidine ranged from 1 \u003cem\u003e\u0026micro;g\u003c/em\u003e to 15 \u003cem\u003e\u0026micro;g\u003c/em\u003e, and the dosages of local anesthetics varied among the studies.\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e Diagram illustrates the complete process of study inclusion.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;1 offers a comprehensive overview of all studies included in this meta-analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eBias assessment\u003c/h2\u003e \u003cp\u003eAfter bias assessment, the 14 RCTs assessed with RoB 2 mostly showed low bias (green), but some had high bias (red) in blinding [13, 21, 35] and unclear bias (yellow) in selective reporting or other domains. For the 2 non-randomized studies using ROBINS-I, Priyaranjan et al had critical/high bias (red) in confounding and selection, while Kosar et al showed low bias overall with moderate bias (yellow) in selective reporting. Overall, the RCTs had fewer bias concerns than the non-randomized studies. For more information the bias assessment of included studies was clarified in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003ea, \u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003eb.\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003ea Assessment of bias for all randomized trials included in in this study.\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003eb Assessment of bias for both nonrandomized trials included in this study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eOnset of Anesthesia\u003c/h2\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e3\u003c/span\u003e (a) Mean onset time for nerve blockade in seconds with 95% CI for dexmedetomidine versus control.\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e3\u003c/span\u003eb Subgroup mean onset time for maxillary and mandibular nerve blockade with 95% CI for dexmedetomidine.\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e3\u003c/span\u003ec Subgroup mean onset time for nerve blockade in seconds with 95% CI for dexmedetomidine \u003cem\u003e1\u0026micro;g/ml.\u003c/em\u003e\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e3\u003c/span\u003ed Subgroup mean onset time for nerve blockade in seconds with 95% CI for dexmedetomidine compared to lidocaine.\u003c/p\u003e \u003cp\u003eOf 16 studies, 12 ones assessed the onset time of anesthesia; however, eight studies (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;560) had sufficient information to allow for pooling [4, 21\u0026ndash;24, 35, 37, 38]. The addition of dexmedetomidine significantly decreased the onset time of anesthesia of nerve blockade by an average of -48.78 seconds in comparison to the control (95\u003cem\u003e% CI\u003c/em\u003e: -64.22 to -33.35; \u003cem\u003eI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;95\u003cem\u003e%\u003c/em\u003e), favouring dexmedetomidine, with a highly significant overall effect (\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.20, p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). Subgroup analyses were performed because the heterogeneity was above our predefined cutoff. Studies were grouped according to mandibular comparing to maxillary anesthesia (Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e3\u003c/span\u003eb), dexmedetomidine concentration1 \u003cem\u003e\u0026micro;g/mL\u003c/em\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e3\u003c/span\u003ec), and lidocaine (Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e3\u003c/span\u003ed). The mandibular anesthesia meta-analysis mean difference was \u0026minus;\u0026thinsp;47.94 seconds (95% \u003cem\u003eCI\u003c/em\u003e: -74.01 to -21.86), showing a faster onset favouring dexmedetomidine. Heterogeneity was high (\u003cem\u003eI\u0026sup2;\u003c/em\u003e = 98%). Maxillary Anesthesia mean difference was \u0026minus;\u0026thinsp;49.88 seconds (95\u003cem\u003e% CI\u003c/em\u003e: -63.76 to -35.99), with significant efficacy in reducing onset time and slightly high heterogeneity (\u003cem\u003eI\u0026sup2;\u003c/em\u003e = 62\u003cem\u003e%\u003c/em\u003e). While the subgroup for one \u0026micro;g/mL dexmedetomidine showed a mean difference of -43.72 seconds (95% \u003cem\u003eCI\u003c/em\u003e: -59.69 to -27.76). This consistent improvement underlines the effective concentration used, though with high heterogeneity (\u003cem\u003eI\u0026sup2;\u003c/em\u003e = 94%). It was even stronger when put in relation to lidocaine, and the mean difference was \u0026minus;\u0026thinsp;49.09 seconds (95% \u003cem\u003eCI\u003c/em\u003e: -60.11, -38.08). The heterogeneity was lower than the others, with \u003cem\u003eI\u0026sup2;\u003c/em\u003e = 83\u003cem\u003e%\u003c/em\u003e, indicating some variability yet a strong general effect.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eDuration of Anesthesia\u003c/h2\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e4\u003c/span\u003e Mean duration of nerve blockade in minutes with 95% CI for dexmedetomidine versus control patients.\u003c/p\u003e \u003cp\u003eOut of 16 studies, 13 revealed the duration time of anesthesia, but only seven studies had sufficient information to allow for pooling [2, 4, 20, 22, 24, 36, 37]. The meta-analysis compiled data from the seven studies involving 534 patients, with 267 assigned to the dexmedetomidine group and 267 to the control group. The pooled results showed a mean difference of 31.10 minutes (95\u003cem\u003e%\u003c/em\u003e confidence interval: 13.77 to 48.43) in favour of the dexmedetomidine group. The findings were statistically significant, with a \u003cem\u003eZ\u003c/em\u003e-value of 3.52 and a \u003cem\u003ep\u003c/em\u003e-value of 0.0004. However, the meta-analysis showed significant heterogeneity among the included studies, with an \u003cem\u003eI\u0026sup2;\u003c/em\u003e value of 94\u003cem\u003e%\u003c/em\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e4\u003c/span\u003e). This high degree of heterogeneity suggests that there might be significant changes in methodology, type of local anaesthetics used, study designs, and patient demographics\u0026mdash;all elements that could affect results.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eAnalgesic Duration\u003c/h2\u003e \u003cp\u003eFigure\u0026nbsp;5 Mean duration of postoperative analgesia in minutes with 95% CI for dexmedetomidine versus control patients.\u003c/p\u003e \u003cp\u003eThe meta-analysis synthesized findings from four studies [2, 21, 23, 35] involving 270 patients\u0026mdash;135 in the dexmedetomidine group and 135 in the control group. Each study measured the duration of analgesia following the administration of dexmedetomidine alongside conventional local anesthetics. The dexmedetomidine group and the control group mean difference in analgesia duration was 186.19 minutes (95\u003cem\u003e% CI\u003c/em\u003e: 109.09 to 263.29); statistical analysis revealed a high level of significance, with a \u003cem\u003eZ\u003c/em\u003e-value of 4.73 and a \u003cem\u003ep\u003c/em\u003e-value of \u0026lt;\u0026thinsp;0.00001 (Fig.\u0026nbsp;5). Overall, seven studies [2, 3, 21, 23, 35, 39] reported that the addition of dexmedetomidine significantly decreased postoperative analgesic requirement at12 to 24 hours or more in comparison to control. The amount of postoperative analgesic drug consumed during 24h of following by the patients exposed to dexmedetomidine combined with local anesthesia was significantly less than standard local anesthesia with \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 [2, 23, 35]. Duration of postoperative analgesia was determined by measuring the time from the end of the procedure until the patient's pain score reached a predefined threshold (e.g., \u003cem\u003eVAS\u003c/em\u003e\u0026thinsp;\u0026ge;\u0026thinsp;3) or they requested rescue analgesia [21, 23]. Patients were commonly prescribed a combination of analgesics, including Paracetamol, Diclofenac Potassium, Enzoflam, Ketorolac Tromethamine, and pethidine, for pain relief [2, 21, 23, 39]. The studies also documented the use of rescue analgesics, typically intravenous Tramadol, for breakthrough pain when the \u003cem\u003eVAS\u003c/em\u003e score was \u0026ge;\u0026thinsp;4 [2, 23]. Because of the different analgesics used and the lack of sufficient reporting to allow for pooling, we could not estimate the effect of this outcome.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003ePost-operative Pain Management and Follow-up\u003c/h2\u003e \u003cp\u003eThe included studies emphasised the importance of postoperative pain management and follow-up in dental procedures, particularly third molar extractions, which are known to induce moderate to severe pain [21, 35]. Varied pain scores and follow-up protocols were used within the first 12 to 24 hours after surgery to evaluate the efficacy of various anaesthetic procedures. The Visual Analogue Scale (\u003cem\u003eVAS\u003c/em\u003e) was widely employed in seven included investigations [2, 3, 23, 24, 35, 38, 39], requiring patients to mark their pain level on a 10-centimetre line ranging from 10 (worst agony possible) to 0 (no pain). However, just one study used the Faces Pain Scale (FPS) [21], which depicts varying levels of pain through a sequence of facial emotions ranging from smiling to crying (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Pain intensity was measured regularly after the surgery to improve patient comfort and check analgesia effectiveness. The studies assessed pain at various time intervals following surgery, including 1, 3, 6, and 12 hours [21, 35, 38]. This enabled researchers to monitor the progression of pain alleviation and identify potential rebound pain.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIndividual study data for postoperative pain comparing dexmedetomidine and control at 12\u0026ndash;24-hours follow-up.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStudy ID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDexmedetomidine\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e Value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePain Scoring System Used\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMain (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMain (SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBhardwaj et al ,2024 [38]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVisual Analog Scale (VAS), postoperative pain score at 12 h\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDoshi et al,\u003c/p\u003e \u003cp\u003e2024 [21]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.22 (0.56) h\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.54 (0.38) h\u0026dagger; \u003c/p\u003e \u003cp\u003e2.1 (0.38) h\u0026dagger;*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFace Pain Scale (FPS), pain score reached a level of 3 or higher, the time was recorded, (\u0026dagger;or \u0026dagger; *) Another 2 groups\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatil et al, \u003c/p\u003e \u003cp\u003e2022 [35]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVisual Analog Scale (VAS), postoperative pain score at 24 hours, Estimated from figure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuryawanshi et al,\u003c/p\u003e \u003cp\u003e2022 [23]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e443.60 \u003c/p\u003e \u003cp\u003e99.28) min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e332.50 \u003c/p\u003e \u003cp\u003e(73.20) min\u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVisual Analog Scale (VAS), \u0026Dagger;The time recorded from the point of completion of the extraction (In maxillary) to the time when the pain intensity was scored\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuryawanshi et al,\u003c/p\u003e \u003cp\u003e2022 [23]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e446.12 \u003c/p\u003e \u003cp\u003e(86.32) min \u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e335.13\u003c/p\u003e \u003cp\u003e(69.82) min \u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVisual Analog Scale (VAS), \u0026Dagger;The time recorded from the point of completion of the extraction (In mandibular) to the time when the pain intensity was scored\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElsawy et al,\u003c/p\u003e \u003cp\u003e2021[2]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2,3) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (3,3) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVisual Analog Scale (VAS) pain score during 24 hours of follow up, *Interquartile range\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePriyaranjan et al, \u003c/p\u003e \u003cp\u003e2020 [3]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVisual Analog Scale (VAS) pain score\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingh et al, 2017 [24]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot specified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNot specified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNot \u003c/p\u003e \u003cp\u003especified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVisual Analog Scale (VAS)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlizargar et al, 2021[39]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.60 (2.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.00 (2.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVisual Analog Scale (VAS), postoperative pain score at 24 hours\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eSedation Effect\u003c/h2\u003e \u003cp\u003eA few studies specifically investigated the sedation side effects of dexmedetomidine when used as an adjunct to local anesthesia. For instance, Etemadi et al. found that patients receiving dexmedetomidine during third molar surgery felt significantly more relaxed than those in the control group[13]. Ouchi and Sugiyama found that increasing concentrations of dexmedetomidine led to an increase in sedation scores [36]. However, it is essential to keep in mind that no participant in any of the studies reported experiencing profound sedation. The remaining studies acknowledged the positive properties of dexmedetomidine as part of its mechanism of action but did not focus on this aspect as a primary outcome [19, 22].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eHaemodynamic Event\u003c/h2\u003e \u003cp\u003eMost of the involved studies found no significant changes in heart rate, systolic blood pressure, diastolic blood pressure, or oxygen saturation when comparing a local anesthetic combined with dexmedetomidine to a local anesthetic alone or a local anesthetic with adrenaline [2, 3, 19\u0026ndash;24, 35\u0026ndash;37]. While several studies noted a drop in either heart rate or blood pressure in the dexmedetomidine group, these usually were slight and did not lead to hypotension or bradycardia [3, 4, 19, 20]. One study even noted that oxygen saturation was greater in the dexmedetomidine group [19]. Regarding the meta-analysis of Intraoperative heart rate(30 minutes), among seven studies (350 patients) [21, 23, 24, 35, 38\u0026ndash;40], the mean difference was 0.10 \u003cem\u003ebpm\u003c/em\u003e (95% \u003cem\u003eCI\u003c/em\u003e: -1.02 to 1.23), indicating no significant impact (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.86). Heterogeneity was low (\u003cem\u003eI\u0026sup2;\u003c/em\u003e = 12\u003cem\u003e%\u003c/em\u003e). Heart rate at 120 minutes, from three studies (150 patients) [21, 35, 40], the mean difference was 0.00 bpm (95\u003cem\u003e% CI\u003c/em\u003e: -1.20 to 1.20), also showing no significant effect impact (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.00). With no heterogeneity (\u003cem\u003eI\u0026sup2;\u003c/em\u003e = 0%). While heart rate at postoperative, from four studies (200 patients) [23, 24, 38, 39], the mean difference was 1.72 bpm (95% \u003cem\u003eCI\u003c/em\u003e: -1.59 to 4.02), also showing no significant effect impact (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.14), With low heterogeneity (\u003cem\u003eI\u0026sup2;\u003c/em\u003e = 20%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe meta-analysis evaluated the effect of dexmedetomidine on systolic blood pressure intraoperatively (30 min), 120 minutes, and postoperatively. Intraoperative systolic pressure, among seven studies (350 patients) ) [21, 23, 24, 35, 38\u0026ndash;40], the mean difference was \u0026minus;\u0026thinsp;0.13 mmHg (95% \u003cem\u003eCI\u003c/em\u003e: -1.53 to 1.80), showing no significant impact (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.88) with no heterogeneity (\u003cem\u003eI\u0026sup2;\u003c/em\u003e = 0\u003cem\u003e%\u003c/em\u003e). Subgroup analysis of Systolic pressure at 120 minutes for three studies (150 patients) ) [21, 35, 40], the mean difference was \u0026minus;\u0026thinsp;1.65 \u003cem\u003emmHg\u003c/em\u003e (95% \u003cem\u003eCI\u003c/em\u003e: -0.68 to 3.98), also indicating no significant effect (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.16) and no heterogeneity (\u003cem\u003eI\u0026sup2;\u003c/em\u003e = 0%). Whereas, postoperatively systolic blood pressure, from four studies (200 patients) [23, 24, 38, 39], the mean difference was \u0026minus;\u0026thinsp;2.15 bpm (95% \u003cem\u003eCI\u003c/em\u003e: -4.64 to 0.34), showing no significant effect impact (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.09) with low heterogeneity (\u003cem\u003eI\u0026sup2;\u003c/em\u003e = 49\u003cem\u003e%\u003c/em\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur meta-analysis also clarified the impact of dexmedetomidine on diastolic blood pressure during surgery (30 minutes), 120 minutes, and postoperatively. Intraoperative Diastolic Pressure, across seven studies (350 patients) ) [21, 23, 24, 35, 38\u0026ndash;40], the mean difference was \u0026minus;\u0026thinsp;0.13 mmHg (95% \u003cem\u003eCI\u003c/em\u003e: -1.53 to 1.80), with no significant effect (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.88) with no heterogeneity (\u003cem\u003eI\u0026sup2;\u003c/em\u003e = 0\u003cem\u003e%\u003c/em\u003e). Diastolic pressure at 120 minutes, among three studies (150 patients) ) [21, 35, 40], the mean difference was 1.65 \u003cem\u003emmHg\u003c/em\u003e (95\u003cem\u003e% CI\u003c/em\u003e: -0.68 to 3.98), again showing no significant impact (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.16) and no heterogeneity (\u003cem\u003eI\u0026sup2;\u003c/em\u003e = 0%). In addition, in four studies (200 patients) at postoperative [23, 24, 38, 39], the mean difference was \u0026minus;\u0026thinsp;2.15 mmHg (95% \u003cem\u003eCI\u003c/em\u003e: -4.64 to 0.34), again showing no significant impact (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.09) and low heterogeneity (\u003cem\u003eI\u0026sup2;\u003c/em\u003e = 49%) (Fig.\u0026nbsp;8). Furthermore, the oxygen saturation meta-analysis also performed with five studies included [23, 24, 35, 38, 39], the mean difference was \u0026minus;\u0026thinsp;0.00 \u003cem\u003eSpO\u003c/em\u003e\u003csub\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sub\u003e (95\u003cem\u003e% CI\u003c/em\u003e: -0.11 to 0.10), with no significant effect (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.94) with no heterogeneity (\u003cem\u003eI\u0026sup2;\u003c/em\u003e = 0%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e6\u003c/span\u003e Mean heart rate risk difference with 95% confidence interval in dexmedetomidine patients versus control.\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e7\u003c/span\u003e Mean systolic blood pressure risk difference with 95% confidence interval for dexmedetomidine versus control patients.\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;8 Mean diastolic blood pressure risk difference with 95% confidence interval for dexmedetomidine versus control patients.\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e9\u003c/span\u003e Mean diastolic oxygen saturation risk difference with 95% confidence interval for dexmedetomidine versus control patients.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur systematic review and meta-analysis support that dexmedetomidine can be used with dental local anaesthesia as an effective adjuvant, significantly shortening the onset time by an average of 48.78 seconds, making the anaesthesia more effective. Furthermore, it extended the duration of anaesthesia by an average of 31.10 minutes, which is good for prolonged surgeries, and improved patient comfort by possibly decreasing the number of additional injections. These findings agreed with other systematic reviews and meta-analyses describing dexmedetomidine's efficacy in many clinical practices. For instance, Hussain et al. investigated dexmedetomidine, which significantly increased both the onset and duration of sensory and motor block durations in brachial plexus blocks [16]. Specifically, they observed a reduction in sensory block onset time by 3.19 minutes and a prolongation of sensory block duration by 261.41 minutes12. Similarly, motor block onset was reduced by 2.92 minutes, with duration prolonged by 200.9 minutes [16]. Further supporting the finding regarding the extended duration of anaesthesia with dexmedetomidine, Abdallah et al., in their systematic review and meta-analysis, found that dexmedetomidine used in neuraxial and peripheral nerve blocks, prolonged sensory block duration by 150 minutes with intrathecal administration [12]. Another study focusing on dexmedetomidine as an adjunct to local anaesthetics in an erector spinae plane block (ESPB) observed a prolonged duration of anaesthesia and reduced postoperative analgesic demand [17]. The studies mentioned above, and others focusing on upper extremity nerve blocks consistently demonstrate dexmedetomidine's benefits in enhancing onset times across different procedural contexts [5]. This finding suggests that dexmedetomidine as an adjuvant to local anaesthesia had potential benefits that extend beyond dental procedures to various clinical settings.\u003c/p\u003e \u003cp\u003eIn terms of postoperative pain management, our meta-analysis showed a significantly prolonged duration of analgesia, with a mean of 186.19 minutes and reduced postoperative analgesic demands with dexmedetomidine. This also concurs with other studies in different clinical scenarios. For example, Wu et al., in their meta-analysis on neuraxial applications of dexmedetomidine, reported significantly enhanced analgesic duration [41]. Similarly, a study by Zhao et al. on femoral nerve blocks further confirmed that dexmedetomidine augmented postoperative pain control [11]. Our studies also reported that from the safety perspective, no serious adverse changes in heart rate, blood pressure, and oxygen saturation were related to dexmedetomidine. The minor fluctuations in heart rate or blood pressure occasionally did not progress to clinically significant hypotension or bradycardia, consistent with other meta-analyses where transient, easily managed bradycardia was noted [11, 16]. The low incidence of postoperative adverse events in dentistry in the current review compared to other systematic reviews and meta-analyses reporting some hypotension or bradycardia may be explained by the low dose of dexmedetomidine used in most of our included studies, 1 \u003cem\u003e\u0026micro;g/ml\u003c/em\u003e. This suggests that dexmedetomidine is safe and effective for managing dental postoperative pain, especially in low dosages.\u003c/p\u003e \u003cp\u003eConsidering these positive outputs, we need to point out some limitations that must be considered in our study. A high degree of heterogeneity was demonstrated, suggesting variability in methodological differences, variations in the type of anaesthetic agents used, and differences in the demographics of the patients included. This heterogeneity complicates the pooling of data, especially regarding the consumption of postoperative analgesics, as inconsistent reporting across studies impedes a detailed assessment regarding the role of dexmedetomidine for pain management. That would then require future studies to standardise methodologies and report trials to integrate data better. It would also be interesting to study the effect of different doses and long-term effects of dexmedetomidine in a wide range of patients to establish further the drug's utility and safety in dental anaesthesia.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn general, this study has provided evidence for the benefits of dexmedetomidine as an adjunct to local anaesthesia in dentistry. As an adjuvant, dexmedetomidine can exhibit multiple advantages with low dosage, including faster onset and prolonged duration of anaesthesia, better postoperative pain control, and a good safety profile. Some heterogeneity in specific analyses and limitations in data availability are needed for further research.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have given consent for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original data presented in this article are available upon reasonable request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere is no competing interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo external funding was received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSAA, WAA, TW, and NL contributed to the conceptualization and study design. SAA and WAA collected and extracted the data. SAA, WAA, and NL performed data analysis and interpretation. All authors SAA, WAA, NL, TW, WW, MW, and YQH were involved in the writing or revision of the manuscript and approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eEl-Boghdadly, K., et al., \u003cem\u003ePerineural Dexmedetomidine Is More Effective Than Clonidine When Added to Local Anesthetic for Supraclavicular Brachial Plexus Block: A Systematic Review and Meta-analysis.\u003c/em\u003e Anesth Analg, 2017. \u003cstrong\u003e124\u003c/strong\u003e(6): p. 2008-2020 DOI: https://doi.org/10.1213/ANE.0000000000002014.\u003c/li\u003e\n \u003cli\u003eElsawy, A. and A.M. Khalifa, \u003cem\u003eDexmedetomidine is an excellent additive to local anaesthesia for postoperative analgesia in bilateral third molar teeth extraction surgery.\u003c/em\u003e Al-Azhar International Medical Journal, 2021. \u003cstrong\u003e2\u003c/strong\u003e(3): p. 30-36 DOI: https://doi.org/10.21608/aimj.2021.66816.1430.\u003c/li\u003e\n \u003cli\u003ePriyaranjan, et al., \u003cem\u003eA Comparative Study Evaluating the Efficacy of Lignocaine and Dexmedetomidine with Lignocaine and Adrenaline in Third Molar Surgery.\u003c/em\u003e Journal of Maxillofacial \u0026amp; Oral Surgery, 2022. \u003cstrong\u003e21\u003c/strong\u003e(2): p. 634-638 DOI: https://doi.org/10.1007/s12663-020-01477-x.\u003c/li\u003e\n \u003cli\u003eKumar, P., et al., \u003cem\u003eThe newer aspect of dexmedetomidine use in dentistry: As an additive to local anesthesia, initial experience, and review of literature.\u003c/em\u003e Natl. j. maxillofac. surg., 2016. \u003cstrong\u003e7\u003c/strong\u003e(1): p. 76-79 DOI: https://doi.org/10.4103/0975-5950.196137.\u003c/li\u003e\n \u003cli\u003eSong, Z.-G., et al., \u003cem\u003eComparison of postoperative analgesic effects in response to either dexamethasone or dexmedetomidine as local anesthetic adjuvants: a systematic review and meta-analysis of randomized controlled trials.\u003c/em\u003e Journal of anesthesia, 2021. \u003cstrong\u003e35\u003c/strong\u003e: p. 270-287 DOI: https://doi.org/10.1007/s00540-021-02895-y.\u003c/li\u003e\n \u003cli\u003eKarmaniolou, I., C. Staikou, and P. Surda, \u003cem\u003eThe role of dexmedetomidine as an additive to intravenous regional anesthesia: a systematic review and meta-analysis.\u003c/em\u003e Balkan Medical Journal, 2021. \u003cstrong\u003e38\u003c/strong\u003e(3): p. 156 DOI: https://doi.org/10.5152/balkanmedj.2021.20076.\u003c/li\u003e\n \u003cli\u003eWang, K., et al., \u003cem\u003eDexmedetomidine combined with local anesthetics in thoracic paravertebral block: A systematic review and meta-analysis of randomized controlled trials.\u003c/em\u003e Medicine (Baltimore), 2018. \u003cstrong\u003e97\u003c/strong\u003e(46): p. e13164 DOI: https://doi.org/10.1097/MD.0000000000013164.\u003c/li\u003e\n \u003cli\u003eTsaousi, G.G., et al., \u003cem\u003eDexmedetomidine as a sedative and analgesic adjuvant in spine surgery: a systematic review and meta-analysis of randomized controlled trials.\u003c/em\u003e European journal of clinical pharmacology, 2018. \u003cstrong\u003e74\u003c/strong\u003e: p. 1377-1389 DOI: https://doi.org/10.1007/s00228-018-2520-7.\u003c/li\u003e\n \u003cli\u003eHemavathi, U., et al., \u003cem\u003eEvaluation of Analgesic Efficacy of Dexmedetomidine as an Adjuvant to Local Anaesthesia in Maxillofacial Soft Tissue Injuries: A Prospective Randomised Clinical Trial.\u003c/em\u003e Journal of Maxillofacial \u0026amp; Oral Surgery, 2024 DOI: https://doi.org/10.1007/s12663-024-02122-7.\u003c/li\u003e\n \u003cli\u003eLiu, D., et al., \u003cem\u003eEfficaciousness of dexmedetomidine in children undergoing cleft lip and palate repair: a systematic review and meta-analysis.\u003c/em\u003e BMJ Open, 2021. \u003cstrong\u003e11\u003c/strong\u003e(8): p. e046798 DOI: https://doi.org/10.1136/bmjopen-2020-046798.\u003c/li\u003e\n \u003cli\u003eZhao, Z.-F., L. Du, and D.-X. Wang, \u003cem\u003eEffects of dexmedetomidine as a perineural adjuvant for femoral nerve block: A systematic review and meta-analysis.\u003c/em\u003e Plos One, 2020. \u003cstrong\u003e15\u003c/strong\u003e(10) DOI: https://doi.org/10.1371/journal.pone.0240561.\u003c/li\u003e\n \u003cli\u003eAbdallah, F. and R. Brull, \u003cem\u003eFacilitatory effects of perineural dexmedetomidine on neuraxial and peripheral nerve block: a systematic review and meta-analysis.\u003c/em\u003e British journal of anaesthesia, 2013. \u003cstrong\u003e110\u003c/strong\u003e(6): p. 915-925 DOI: https://doi.org/10.1093/bja/aet066.\u003c/li\u003e\n \u003cli\u003eEtemadi Sh, M., et al., \u003cem\u003eEffect of Dexmedetomidine Added to Lidocaine Cartridge on the Level of Patient Sedation, Cooperation, and Patient and Surgeon Satisfaction during Mandibular Third-Molar Extraction Surgery: A Randomized Double-Blind Controlled Trial.\u003c/em\u003e International Journal of Dentistry, 2022. \u003cstrong\u003e2022\u003c/strong\u003e DOI: https://doi.org/10.1155/2022/4722674.\u003c/li\u003e\n \u003cli\u003eVahedi, Z., A. Moshari, and M. Moshari, \u003cem\u003eEfficacy of adding dexmedetomidine to lidocaine to enhance inferior alveolar nerve block in patients with asymptomatic irreversible pulpitis: double-blind randomized clinical trial.\u003c/em\u003e Clinical Oral Investigations, 2022. \u003cstrong\u003e26\u003c/strong\u003e(7): p. 4727-4734 DOI: https://doi.org/10.1007/s00784-022-04436-7.\u003c/li\u003e\n \u003cli\u003eAlsultan, D., \u003cem\u003eEfficacy of dexmedetomidine as an adjuvant in transverse abdominal plane blocks for cesarean section pain management: A systematic review and meta-analysis.\u003c/em\u003e Saudi Journal of Anaesthesia, 2024. \u003cstrong\u003e18\u003c/strong\u003e(4): p. 545-555 DOI: https://doi.org/10.4103/sja.sja_306_24.\u003c/li\u003e\n \u003cli\u003eHussain, N., et al., \u003cem\u003eInvestigating the Efficacy of Dexmedetomidine as an Adjuvant to Local Anesthesia in Brachial Plexus Block: A Systematic Review and Meta-Analysis of 18 Randomized Controlled Trials.\u003c/em\u003e Reg Anesth Pain Med, 2017. \u003cstrong\u003e42\u003c/strong\u003e(2): p. 184-196 DOI: https://doi.org/10.1097/aap.0000000000000564.\u003c/li\u003e\n \u003cli\u003eLiang, Y., S. Xiaojuan, and L. He, \u003cem\u003eThe effect and safety of dexmedetomidine as an adjuvant to local anesthetics in erector spinae plane block: a systematic review and meta-analysis of randomized controlled trials.\u003c/em\u003e 2023 DOI: https://doi.org/10.1186/s12871-023-02019-x.\u003c/li\u003e\n \u003cli\u003eAlbrecht, E., et al., \u003cem\u003eDexamethasone Is Superior to Dexmedetomidine as a Perineural Adjunct for Supraclavicular Brachial Plexus Block: Systematic Review and Indirect Meta-analysis.\u003c/em\u003e Anesth Analg, 2019. \u003cstrong\u003e128\u003c/strong\u003e(3): p. 543-554 DOI: https://doi.org/10.1213/ANE.0000000000003860.\u003c/li\u003e\n \u003cli\u003eNalawade, S., et al., \u003cem\u003eA clinical comparative study of dexmedetomidine as an adjuvant to 2% plain lignocaine and 2% lignocaine with 1: 200,000 adrenaline as local anesthetic agents for surgical removal of impacted mandibular third molars.\u003c/em\u003e Natl. j. maxillofac. surg., 2021. \u003cstrong\u003e12\u003c/strong\u003e(2): p. 255-261 DOI: https://doi.org/10.4103/njms.NJMS_7_20.\u003c/li\u003e\n \u003cli\u003eOuchi, K., \u003cem\u003eDexmedetomidine 2\u0026thinsp;ppm Is Appropriate for the Enhancement Effect of Local Anesthetic Action of Lidocaine in Inferior Alveolar Nerve Block: a Preliminary, Randomized Cross-over Study.\u003c/em\u003e Clinical journal of pain, 2020. \u003cstrong\u003e36\u003c/strong\u003e(8): p. 618‐625 DOI: https://doi.org/10.1097/AJP.0000000000000839.\u003c/li\u003e\n \u003cli\u003eDoshi, A., N. Bhola, and A. Agarwal, \u003cem\u003eComparing the efficacy of adrenaline, clonidine, and dexmedetomidine in enhancing local anesthesia for impacted third molar extraction: a randomized controlled trial.\u003c/em\u003e Journal of dental anesthesia and pain medicine, 2024. \u003cstrong\u003e24\u003c/strong\u003e(4): p. 285‐295 DOI: https://doi.org/10.17245/jdapm.2024.24.4.285.\u003c/li\u003e\n \u003cli\u003eKhandaitkar, S., et al., \u003cem\u003eA clinical study to determine the efficacy of 7ppm dexmedetomidine as an adjuvant to 2% lignocaine in infraorbital nerve block.\u003c/em\u003e The British journal of oral \u0026amp; maxillofacial surgery, 2016. \u003cstrong\u003e54\u003c/strong\u003e(9): p. 997-1000 DOI: https://dx.doi.org/10.1016/j.bjoms.2016.07.011.\u003c/li\u003e\n \u003cli\u003eSuryawanshi, T., et al., \u003cem\u003eComparative Analysis of Anaesthetic Efficacy of 2% Lignocaine With Dexmedetomidine as an Adjunct in Nerve Blocks for Dental Extractions: A Randomised Controlled Study.\u003c/em\u003e Cureus, 2022. \u003cstrong\u003e14\u003c/strong\u003e(9) DOI: https://doi.org/10.7759/cureus.28867.\u003c/li\u003e\n \u003cli\u003eSingh, V., et al., \u003cem\u003eDexmedetomidine as an Additive to Local Anesthesia: A Step to Development in Dentistry.\u003c/em\u003e Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons, 2018. \u003cstrong\u003e76\u003c/strong\u003e(10): p. 2091.e1-2091.e7 DOI: https://dx.doi.org/10.1016/j.joms.2018.05.037.\u003c/li\u003e\n \u003cli\u003eRyu, D.-S., et al., \u003cem\u003eSedation protocol using dexmedetomidine for third molar extraction.\u003c/em\u003e Journal of Oral and Maxillofacial Surgery, 2016. \u003cstrong\u003e74\u003c/strong\u003e(5): p. 926. e1-926. e7 DOI: https://doi.org/10.1016/j.joms.2015.12.021.\u003c/li\u003e\n \u003cli\u003ePage, M.J., et al., \u003cem\u003eThe PRISMA 2020 statement: an updated guideline for reporting systematic reviews.\u003c/em\u003e Systematic Reviews, 2021. \u003cstrong\u003e10\u003c/strong\u003e(1): p. 89 DOI: https://doi.org/10.1186/s13643-021-01626-4.\u003c/li\u003e\n \u003cli\u003eSterne, J.A.C., et al., \u003cem\u003eRoB 2: a revised tool for assessing risk of bias in randomised trials.\u003c/em\u003e Bmj, 2019. \u003cstrong\u003e366\u003c/strong\u003e: p. l4898 DOI: https://doi.org/10.1136/bmj.l4898.\u003c/li\u003e\n \u003cli\u003eIgelstr\u0026ouml;m, E., et al., \u003cem\u003eCochrane\u0026apos;s risk of bias tool for non-randomized studies (ROBINS-I) is frequently misapplied: A methodological systematic review.\u003c/em\u003e J Clin Epidemiol, 2021. \u003cstrong\u003e140\u003c/strong\u003e: p. 22-32 DOI: https://doi.org/10.1016/j.jclinepi.2021.08.022.\u003c/li\u003e\n \u003cli\u003eMansour, R.F. and M.S. Abdelghany, \u003cem\u003eUltrasound-guided suprazygomatic maxillary nerve block in cleft palate surgery: The efficacy of adding dexmedetomidine to bupivacaine.\u003c/em\u003e Egyptian Journal of Anaesthesia, 2021. \u003cstrong\u003e37\u003c/strong\u003e(1): p. 329-336 DOI: https://doi.org/10.1080/11101849.2021.1953832.\u003c/li\u003e\n \u003cli\u003eMostafa, M.F., et al., \u003cem\u003eDexmedetomidine during suprazygomatic maxillary nerve block for pediatric cleft palate repair, randomized double-blind controlled study.\u003c/em\u003e Korean Journal of Pain, 2020. \u003cstrong\u003e33\u003c/strong\u003e(1): p. 81-89 DOI: https://doi.org/10.3344/kjp.2020.33.1.81.\u003c/li\u003e\n \u003cli\u003eAlansary, A.M., M.M. Ali, and M.A. Elshafie, \u003cem\u003eA randomized controlled trial of dexmedetomidine vs magnesium sulfate as adjuvants to bupivacaine in infraorbital nerve block for perioperative analgesia in pediatric patients undergoing cleft lip surgery.\u003c/em\u003e Anaesthesia Pain \u0026amp; Intensive Care, 2023. \u003cstrong\u003e27\u003c/strong\u003e(4): p. 514-522 DOI: https://doi.org/10.35975/apic.v27i4.2261.\u003c/li\u003e\n \u003cli\u003eEl-Emam, E.-S. and E. El motlb, \u003cem\u003eComparative Evaluation of Dexamethasone and Dexmedetomidine as Adjuvants for Bupivacaine in Ultrasound-Guided Infraorbital Nerve Block for Cleft Lip Repair: A Prospective, Randomized, Double-Blind Study.\u003c/em\u003e Anesth Essays Res, 2019. \u003cstrong\u003e13\u003c/strong\u003e(2): p. 354-358 DOI: https://doi.org/10.4103/aer.AER_14_19.\u003c/li\u003e\n \u003cli\u003eStepien, A., P. Stepien, and J. Kornatowska, \u003cem\u003eDEXMEDETOMIDINE AS AN ADDITIVE TO LOCAL ANESTHESIA IN DENTISTRY.\u003c/em\u003e Prospects in Pharmaceutical Sciences, 2024. \u003cstrong\u003e22\u003c/strong\u003e(3): p. 58-61 DOI: https://doi.org/10.56782/pps.211.\u003c/li\u003e\n \u003cli\u003eTonooka, Y. and K. Sunada, \u003cem\u003eDexmedetomidine Enhances the Pulpal Anesthetic Effect of Lidocaine: A Pilot Study.\u003c/em\u003e Anesthesia progress, 2018. \u003cstrong\u003e65\u003c/strong\u003e(1): p. 38-43 DOI: https://doi.org/10.2344/anpr-65-01-05.\u003c/li\u003e\n \u003cli\u003ePatil, S.M., et al., \u003cem\u003eDoes dexmedetomidine combined with levobupivacaine in inferior alveolar nerve blocks among patients undergoing impacted third molar surgery control postoperative morbidity?\u003c/em\u003e Journal of dental anesthesia and pain medicine, 2022. \u003cstrong\u003e22\u003c/strong\u003e(2): p. 145‐153 DOI: https://doi.org/10.17245/jdapm.2022.22.2.145.\u003c/li\u003e\n \u003cli\u003eOuchi, K. and K. Sugiyama, \u003cem\u003eDexmedetomidine Dose Dependently Enhances the Local Anesthetic Action of Lidocaine in Inferior Alveolar Nerve Block: a Randomized Double-Blind Study.\u003c/em\u003e Regional anesthesia and pain medicine, 2016. \u003cstrong\u003e41\u003c/strong\u003e(3): p. 348‐355 DOI: https://doi.org/10.1097/AAP.0000000000000380.\u003c/li\u003e\n \u003cli\u003eKosar, S., et al. \u003cem\u003eUse of Dexmedetomidine in Dentistry as an Additive to Local Anesthesia in Place of Adrenaline\u003c/em\u003e. 2021. \u0026nbsp;DOI: https://doi.org/10.21275/ART20205\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eBhardwaj, S., et al., \u003cem\u003eRopivacaine vs. Ropivacaine-Dexmedetomidine for IANB in Mandibular Third Molar Extraction.\u003c/em\u003e Nanotechnology Perceptions, 2024: p. 948-955 DOI: https://doi.org/10.62441/nano-ntp.v20iS9.69.\u003c/li\u003e\n \u003cli\u003eAlizargar, J., et al., \u003cem\u003eInjection of Lidocaine Alone versus Lidocaine plus Dexmedetomidine in Impacted Third Molar Extraction Surgery, a Double-Blind Randomized Control Trial for Postoperative Pain Evaluation.\u003c/em\u003e Pain research \u0026amp; management, 2021. \u003cstrong\u003e2021\u003c/strong\u003e: p. 6623792 DOI: https://dx.doi.org/10.1155/2021/6623792.\u003c/li\u003e\n \u003cli\u003eYamane, A., et al., \u003cem\u003eEffect of dexmedetomidine injected into the oral mucosa in combination with lidocaine on local anesthetic potency in humans: a\u0026nbsp;crossover double-blind study.\u003c/em\u003e J Oral Maxillofac Surg, 2015. \u003cstrong\u003e73\u003c/strong\u003e(4): p. 616-21 DOI: https://doi.org/10.1016/j.joms.2014.09.029.\u003c/li\u003e\n \u003cli\u003eWu, H.-H., et al., \u003cem\u003eDoes dexmedetomidine as a neuraxial adjuvant facilitate better anesthesia and analgesia? A systematic review and meta-analysis.\u003c/em\u003e PloS one, 2014. \u003cstrong\u003e9\u003c/strong\u003e(3): p. e93114 DOI: https://doi.org/10.1371/journal.pone.0093114.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Dexmedetomidine, Local anesthesia, Dental procedures, Nerve block, Adjuvant anesthetics, Anesthetic efficacy, Pain management, Meta-analysis","lastPublishedDoi":"10.21203/rs.3.rs-5597524/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5597524/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground and Objectives:\u003c/strong\u003e Dexmedetomidine has been considered an effective adjunct to dental local anesthetics. Uncertainty about its efficacy and safety in dental use still remains. This study is primarily designed to evaluate the effectiveness and safety of dexmedetomidine as an adjunct to local anesthesia in dental procedures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e A meta-analysis of controlled trials assessed the effects of dexmedetomidine as an adjunct to local anesthesia in dental procedures, focusing on anesthesia duration and onset time. Studies were identified via multiple databases, and methodological quality was evaluated using ROBINS-I and Cochrane Risk of Bias tools. RevMan V.5.1 was used for heterogeneity analysis, sensitivity analyses, pooling mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CI), and assessing publication bias.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThis meta-analysis included sixteen clinically controlled trials involving 658 patients (\u003cem\u003en\u003c/em\u003e=877 samples). Adding dexmedetomidine significantly reduced onset time by 48.78 seconds (95\u003cem\u003e% CI\u003c/em\u003e: -64.22 to -33.35 seconds) and prolonged analgesia duration by 31.10 minutes (95\u003cem\u003e% CI\u003c/em\u003e: 13.77 to 48.43 minutes). It also significantly increased postoperative analgesic duration by 186.19 minutes (95\u003cem\u003e% CI\u003c/em\u003e: 109.09 to 263.29 minutes). Hemodynamic analysis revealed non-significant changes in heart rate, intraoperative systolic and diastolic pressures, and oxygen saturation. It is important to note that minor heart rate and blood pressure fluctuations did not lead to clinically significant hypotension or bradycardia during dental procedures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003eDexmedetomidine enhances dental local anesthesia by providing quicker onset, longer duration, improved postoperative pain management, and a favorable safety profile, though further research is needed to address variability.\u003c/p\u003e","manuscriptTitle":"Investigating the Efficacy of Dexmedetomidine as an Adjuvant to Local Anesthesia in Dentistry: Systematic Review and Meta Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-11 09:35:38","doi":"10.21203/rs.3.rs-5597524/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2025-08-08T03:08:35+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-01-06T07:46:50+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-01-03T11:39:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-01-03T07:13:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"Systematic Reviews","date":"2024-12-07T02:21:07+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"829f012f-3b97-4f44-b3e6-cbdc8c94c67e","owner":[],"postedDate":"February 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-07T10:12:24+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-11 09:35:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5597524","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5597524","identity":"rs-5597524","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}