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 Table of Contents  
REVIEW ARTICLE
Year : 2023  |  Volume : 13  |  Issue : 1  |  Page : 9-21

Preoperative nonsteroidal anti-inflammatory drugs on the success of inferior alveolar nerve block in irreversible pulpitis: An overview of systematic reviews


1 Department of Conservative Dentistry and Endodontics, Manav Rachna Dental College, Faridabad, Haryana, India
2 Department of Orthodontics and Dentofacial Orthopedics, Manav Rachna Dental College, Faridabad, Haryana, India
3 Department of Conservative Dentistry and Endodontics, Jamia Milia Islamia, New Delhi, India
4 Government Multi Speciality Hospital, Chandigarh, India
5 Consultant and Private Practitioner, Chandigarh, India

Date of Submission02-Mar-2022
Date of Decision29-Apr-2022
Date of Acceptance29-Apr-2022
Date of Web Publication11-Jan-2023

Correspondence Address:
Dr. Alpa Gupta
Department of Conservative Dentistry and Endodontics, Manav Rachna Dental College, Sector – 43, Delhi, Suraj Kund Badkhal Rd., Faridabad - 121 004, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sej.sej_46_22

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  Abstract 

Introduction: The inflammatory conditions of pulp often lead to pain which is managed by adequate anesthesia. Achieving optimum anesthethic effect in such conditions is difficult; therefore, various supplemental techniques have been used to enhance the effect. Premedication is one such technique vastly studied. This study aimed to critically analyze the systematic reviews, including their respective meta-analyses, to summarize the data regarding the role of nonsteroidal anti-inflammatory drugs (NSAIDs) on the success of inferior alveolar nerve block (IANB) in patients with irreversible pulpitis.
Materials and Methods: The protocol was formulated using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist, and the formulated PICO question was “Is there any effect of oral premedication with NSAIDs on the anesthetic success of IANB in irreversible pulpitis?” The reviews were analyzed using a measurement tool to assess systematic reviews (AMSTAR).
Results: Twelve reviews were selected, out of which three were finally included for detailed analysis and their AMSTAR scores were 'high.' Individual meta-analyses results pointed toward the anesthetic success of IANB with NSAIDs as oral premedication.
Conclusion: The current overview justifies the use of NSAIDs by highlighting the supporting and conflicting data of each systematic review.

Keywords: Anesthesia, inferior alveolar nerve block, irreversible pulpitis, nonsteroidal anti-inflammatory drugs, oral premedication


How to cite this article:
Gupta A, Aneja K, Wadhwa J, Aggarwal V, Sidhu S, Mehta N. Preoperative nonsteroidal anti-inflammatory drugs on the success of inferior alveolar nerve block in irreversible pulpitis: An overview of systematic reviews. Saudi Endod J 2023;13:9-21

How to cite this URL:
Gupta A, Aneja K, Wadhwa J, Aggarwal V, Sidhu S, Mehta N. Preoperative nonsteroidal anti-inflammatory drugs on the success of inferior alveolar nerve block in irreversible pulpitis: An overview of systematic reviews. Saudi Endod J [serial online] 2023 [cited 2023 Feb 6];13:9-21. Available from: https://www.saudiendodj.com/text.asp?2023/13/1/9/367516


  Introduction Top


Symptomatic irreversible pulpitis is an inflammatory pulpal condition that leads to sharp pain and is often indicated for root canal treatment. Various factors play a role in mediating the inflammatory process. Inflammatory mediators such as prostaglandins (PGs) E2 and PGI2, which are formed by the cyclo-oxygenase (COX) enzymes, activate the nociceptive neurons through their interaction with specific receptors. These PGs sensitize neurons and overall reduce the activation threshold resulting in an enhanced response to stimuli.[1],[2]

Local anesthesia forms an integral part of managing painful endodontic emergencies. However, local anesthetic efficacy is reduced when injected in patients with inflammatory conditions such as irreversible pulpitis.[3],[4] The IANB is the most commonly used technique to anesthetize mandibular teeth. However, failure of IANB has been reported in 43%–83% of cases of irreversible pulpitis.[5] Anesthetic failure is attributed to multiple causes such as anatomical variations causing an inability to deposit the anesthetic solution at the target area, acute tachyphylaxis to local anesthesia, psychological factors, and inflammation.[1],[6] Hence, it is imperative to augment the anesthetic efficiency of the IANB block for painless and comfortable endodontic treatment.

The increase in the success of mandibular anesthesia in teeth with irreversible pulpitis can be achieved by various techniques such as supplemental buccal infiltration,[7] periodontal ligament injection,[8] intraosseous anesthesia,[9] and oral premedications.[10],[11],[12],[13] Variety of oral pharmacological agents such as steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen alone or in combination with other analgesics, opioids, and benzodiazepines have been investigated by various randomized control trials highlighting the role of these agents in improving the anesthetic efficacy in irreversible pulpitis.[14],[15],[16],[17],[18],[19],[20],[21],[22],[23]

NSAIDs exert their analgesic and anti-inflammatory property by blocking the COX enzymes. The COX enzyme occurs in two isoforms – the COX-1 enzyme is the constitutive form and is involved in a range of physiological functions of the stomach, kidneys, and platelets, while the COX-2 enzyme is the inducible form and is present in pathological conditions like inflammation or tissue injury.[24],[25] Since NSAIDs reduce the levels of inflammatory mediators, mainly PGs, it has been hypothesized that NSAIDs when taken as an oral premedication can affect the success of local anesthesia in patients with irreversible pulpitis.

The corticosteroids, on the other hand, block both the COX and lipoxygenase pathways by reducing the vasodilation, migration of leukocytes, and by inhibiting the formation of arachidonic acid;[14] however, there is only limited literature on the use of steroids for improving the efficacy of IANB.[14],[15]

Another class of drugs that have been investigated for increasing the efficacy of IANB are opioid analgesics such as hydrocodone[26] and tramadol.[21],[27],[28] These act by interaction with specific receptors by binding to them during tissue injury resulting in analgesia.[26] Despite the opioid analgesics having a profound effect on the effect of IANB, they are not much advocated due to their side effects such as sleepiness and nausea.

Benzodiazepines (triazolam and alprazolam) are sedatives that reduce pain-related anxiety by stimulating the Gamma-aminobutyric acid receptors in the spinal cord and act against hyperalgesia.[29] They enhance the concentration of inherent opioids like Enkephalin in areas of the central nervous system related to processing pain. However, premedication with sedatives should be avoided owing to patient's inability to drive themselves home after the treatment. Scanty literature is available on the role of these types of drugs as oral premedication depicting the anesthetic success of IANB.[22],[23]

The classification of acetaminophen is fraught with difficulty. It is a distinct class of analgesics from NSAIDs that works similarly to aspirin but with a mild anti-inflammatory effect on the peripheral nerves. In the presence of peroxides produced at the inflammatory site, acetaminophen is a mild inhibitor of COX. It has already been established that acetaminophen does not improve the efficacy of IANB when used alone, but, when combined with other NSAIDs, it has a considerable effect.[30]

Various randomized control trials have studied the role of NSAIDs on the anesthetic efficacy of IANB. Twelve systematic reviews, with or without meta-analyses, have been published in this regard.[10],[11],[12],[13],[30],[31],[32],[33],[34],[35],[36],[37] Eight of these compared the role of NSAIDs with placebo on the anesthetic success of IANB as one of the interventions. Four systematic reviews solely evaluated the role of NSAIDs with placebo.[10],[13],[33],[37]

Various concerns have been raised regarding these reviews. To begin, whether studies using acetaminophen in conjunction with other analgesics[38],[39] should be included in a systematic review focused solely on NSAIDs.[10],[11] Second, there should be well-defined criteria to evaluate the anesthetic success of IANB with oral premedication on the visual analog scale. Third, whether the studies on asymptomatic irreversible pulpitis should be part of concerned systematic reviews. It has been established that the anesthetic efficacy of IANB is affected by the presence of preoperative pain in cases of symptomatic irreversible pulpitis;[40] accordingly, does asymptomatic irreversible pulpitis also affect the efficacy of IANB?

This overview intends to critically analyze all the systematic reviews with or without meta-analysis including their consistent and conflicting data. Finally, with the help of high evidence level systematic reviews, we will try to interpret the conclusion on the role of NSAIDs on the anesthetic efficacy of IANB in patients with irreversible pulpitis.


  Materials and Methods Top


The protocol for this review was framed using the standard Preferred Reporting Items for Systematic Reviews and Meta-Analyses Checklist,[41] which was then registered in the PROSPERO database (CRD238020). PICO protocol that specifically defines the population, intervention, comparison, and outcome of the study was followed to formulate the review question, which was “Is there any effect of premedication with oral NSAIDs on the anesthetic success of inferior alveolar nerve block in patients with irreversible pulpitis?”

Literature search strategy

An advanced database search was conducted in the MEDLINE/PubMed and Scopus without any language restriction for reviews that were within the scope of this overview. Three examiners separately carried out a systematic database search from inception till November 2020. MeSH (Medical Subject Headings https://www.ncbi.nml.nih.gov/mesh) terms along with Boolean operators “AND” and “OR” were used to formulate a combination of keywords for database search. The following search strategy: (Irreversible pulpitis) AND ((local anesthesia) OR inferior alveolar nerve block) AND ((((NSAIDS) OR oral premedication) OR preoperative medication)) AND ((systematic review) AND (Meta Analyses) were followed to categorize relevant literature. In addition, the bibliography of the included reviews was thoroughly searched manually. Two independent reviewers identified the relevant reviews and any doubts were cleared by a discussion with the third reviewer. The collected literature was extensively searched to identify and exclude duplicates.

Inclusion and exclusion criteria

Systematic reviews that evaluated the efficacy of NSAIDs alone or as part of additional approaches in obtaining pulpal anesthesia in cases of irreversible pulpitis indicated for nonsurgical endodontic treatment were included. The interventions of interest were oral premedication with any NSAID at any dose compared to placebo. The success rate of IANB anesthesia, as measured by pain experienced during root canal access and instrumentation, was the primary outcome of relevance. Systematic reviews that focused solely on NSAIDs but included studies that use acetaminophenen in conjunction with NSAIDs were omitted. Clinical studies, laboratory research, animal studies, and narrative reviews were also excluded.

Data extraction

Data characterisation was explained on the basis of information that includes year, journal name, first author's name, databases searched, time period of the search, type of study, quality assessment tools in the study, outcomes analyzed, number of included studies, and sample size in the study. Meta Analyses was explained on the basis of calculation protocol specific relative risk (RR) estimates with a confidence interval (CI), I square value (I2) (to evaluate heterogeneity), and publication bias.

Primary outcome

Effect of oral premedication with NSAIDs on anestheric success of IANB during root canal access opening and instrumentation.

Secondary outcomes

Any adverse effect of NSAIDs or any rank and dose-related effect of NSAIDs in terms of the anesthetic success of IANB.

Methodological quality assessment

The methodological quality assessment was carried out using the AMSTAR tool consisting of 11 items.[42] Two reviewers individually assessed the quality of included reviews; any disagreements were resolved by the third reviewer. A score of “1” was assigned to the items that met the required criteria. A score of “0” was assigned to any material in the systematic review that was unclear. The reviews were categorized as high, medium, or low quality, with scores ranging from 8 to 11, 4–7, and 0–3, respectively, based on scoring.[43] The inter-examiner agreement on quality analysis of included reviews was calculated using Cohen's kappa analysis.


  Results Top


[Figure 1] depicts the full search and identification method. The total number of studies selected after a search of databases was 1853, and after the initial screening process (title/abstract), 635 studies remained. Twelve reviews were selected for full-text analysis after duplicate exclusion.[10],[11],[12],[13],[30],[31],[32],[33],[34],[35],[36],[37] Five reviews[10],[11],[12],[35],[37] were excluded during the second phase (full-text reading) since they have included studies by Modaresi et al.[44] and Mokhtari et al.[45] who have not given any well-defined criteria for the success of IANB. Furthermore, a review by Li et al.[10] was also excluded. Although the review was exclusive on NSAIDs, it included studies on acetaminophen[38],[39] which is not categorized under NSAIDs. Furthermore, four systematic reviews[33],[34],[35],[36] were excluded since they have included the study by Yadav et al.[46] which does not have a placebo as a control group, thereby defying their inclusion criteria. Two systematic reviews[32],[34] were excluded on the fact that their inclusion criteria were specifically based on studies on patients diagnosed with symptomatic irreversible pulpitis, but they have included a study by Shahi et al.[14] which was on asymptomatic irreversible pulpitis. Finally, three systematic reviews were included[13],[30],[31] as a part of the present overview. Moreover, Tupyota et al.[31] have included studies by Simpson et al. 2011[38] and Ianiro et al. 2007,[39] since it was not exclusively on NSAIDs, hence fits our inclusion criteria.
Figure 1: A flowchart of the screening of studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendation

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Characteristics of included reviews

Characteristics of studies included in systematic reviews and the characteristics of the systematic reviews included in this overview are summarized in [Table 1] and [Table 2], respectively. The systematic reviews were published between 2017 and 2018 in the Australian Endodontic Journal (n = 1), Journal of Endodontics (n = 1), and International Endodontic Journal (n = 1). The specific reviews used MEDLINE/PubMed, Scopus, EBSCOhost, MEDLINE/Ovid, and Cochrane Central Register of Controlled Trials for their respective search to categorize relevant literature in their respective reviews. The period for search within the reviews was till October 2017. Each review had 5–14 studies. All the three included reviews carried out meta-analyses.[13],[30],[31] The risk of bias assessment by Tupyota et al.[31] was done through the Cochrane Handbook for Systematic Reviews of Interventions,[54] while in the other two reviews,[13],[30] revised Cochrane Risk-of-Bias Tool for Randomized Trials (RoB 2.0) was used.[54] Two reviews[13],[30] used the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) method to rate the evidence quality (high, moderate, low, and very low) using GRADE pro-GDT software, whereas one review[31] did not specify any quality analysis tool based on seven domains mentioned in the Cochrane Handbook for Systematic Reviews of Interventions.[55]
Table 1: Characteristics of studies included in the selected reviews

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Table 2: Characteristics of included systematic reviews

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Summary of meta-analyses

All systematic reviews[13],[30],[31] calculated the success rate of pulpal anesthesia as RR with a 95% CI. Forest plots were represented for each included study. I2 depicted heterogeneity. Subgroup analysis was carried out to find statistical significance between groups. The random-effect meta-analyses were used to merge esthetic success rates. In the systematic review by Tupyota et al.,[31] five relevant studies[14],[16],[17],[47],[48] using premedication with NSAIDs showed a statistically significant high success rate of pulpal anesthesia (P = 0.001; random pooled RR = 1.75, 95% CI = 1.24–2.48). I2 = 43% which is <50% indicates statistical heterogeneity was not as significant. A funnel plot revealed no publication bias.

In the systematic review by Nagendrababu et al.,[13] out of all 1034 participants undergoing endodontic treatment, 493 (47.6%) had successful anesthetic outcomes with painless and comfortable root canal treatment procedures. Quantitative pooling of all results showed a significant increase in anesthetic outcome with NSAIDs compared to placebo (RR = 1.96; 95% CI, 1.63–2.35; I2 = 6.8%). Fixed model sensitivity analysis model (RR = 2.07; 95% CI, 1.73–2.47; I2 = 6.8%) showed similar values as the main analysis. Thus, the analysis can be considered reliable, and NSAIDs showed superior efficacy.

For nine trials using ibuprofen (at any dose), significantly increased anesthetic success in the subgroup analysis was found (RR = 1.83; 95% CI, 1.43–2.35; I2 = 20.8%). Stratification on the basis of doses, ibuprofen >400 mg/d was found to be significantly more efficacious as compared to placebo (RR = 1.85; 95% CI, 1.39–2.45; I2 = 26.7%), whereas no significant association was found for ibuprofen ≤400 mg/d (RR = 1.78; 95% CI, 0.90–3.55; I2 = 38.7%). Other NSAIDs, diclofenac 50 mg and ketorolac 10 mg, also showed a statistically significant increase in the IANB success as in comparison with placebo (RR = 2.56; 95% CI, 1.46–4.50; I2 = 44.8% and RR = 2.07; 95% CI, 1.47–2.90; I2 = 0%, respectively).

For NSAIDs, Trial sequential analysis (TSA) for the primary efficacy outcome among 8 trials revealed a low risk of bias. The information size (n = 131) surpassed with a cumulative z statistic above 1.96. This conclusively confirmed the validity of the results of the MA that NSAIDs increased the success of IANB anesthesia. TSAs of subgroups (heterogeneity-adjusted information size: ibuprofen at any dose [n = 190], ibuprofen >400 mg/d [n = 157], ketorolac 10 mg [n = 88], and diclofenac 50 mg [n = 160]) also depicted a positive impact in increasing the anesthetic success of IANB. However, it was found that the sample size for meta-analyses did not exceed the required information size, indicating that the collected evidence was uncertain for ibuprofen ≤400 mg/d. Funnel plot asymmetry and Egger regression tests revealed no publication bias.

Overall, the GRADE evaluation showed the high quality of the accumulated evidence for premedication with NSAIDs for the anesthetic success of IANB. Similarly, GRADE methodology when applied for other interventions (ibuprofen at any dose, ibuprofen >400 mg/d, diclofenac 50 mg, and ketorolac 10 mg) showed that the collective evidence was of high quality.

The results of the systematic review by Pulikkotil et al.[30] performed standard pairwise random-effect meta-analyses, which showed dexamethasone (RR, 3.00 [95% CI: 1.39, 6.48]), NSAIDs (RR, 1.93 [95% CI: 1.63, 2.29]), and NSAIDs + acetaminophen (RR, 1.50 [95% CI: 1.08, 2.08]) led to a significant increase in the success of IANB anesthesia during the treatment procedure. When compared, NSAIDs were revealed to be superior to acetaminophen for IANB success (RR, 4.25 [95% CI: 1.13, 16.03]). No significant difference was found for the comparison of dexamethasone and NSAIDs (RR, 1.64 [95% CI: 0.85, 2.63]).

Network meta-analyses revealed the success rate of all the included trials to be comparable with those from standard pairwise meta-analyses. Assessed for comparative efficacy dexamethasone was superior to all other agents, except NSAIDs, for which the association did not reach significance (RR, 1.52 [95%CI 0.91,2.52]). When individual NSAIDs and other interventions were considered, the network MA showed that, in comparison with placebo, dexamethasone 0.5 mg (RR, 3.29 [95% CI: 1.61, 6.74]) was on top with a significant increase in the success of IANB anesthesia, followed by ketorolac 10 mg (RR, 2.34 [95% CI: 1.74,3.15]), piroxicam 20 mg (RR, 2.40 [95% CI: 1.36, 4.21]), ibuprofen 400 mg + acetaminophen 500 mg (RR, 2.42 [95% CI: 1.25, 4.68]), and tramadol 50 mg (RR, 2.28 [95%CI: 1.18, 4.39]). However, aceclofenac 100 mg, ibuprofen 300 mg, and naproxen 550 mg could not show any significant associations for primary efficacy outcome. Similarly, no significant association was found for acetaminophen (any dose), alprazolam, and some other combinations. The funnel plot revealed no publication bias.

On applying GRADE criteria, high, moderate, and low confidence estimates supported NSAIDs, dexamethasone, and tramadol, for use as premedication for the success of IANB anesthesia. The high quality was assigned that showed no difference for the comparison of NSAIDs with the combination of NSAIDs and acetaminophen. [Table 3] shows the overall summary of meta-analyses.
Table 3: Summary of meta-analysis

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Methodological quality

The methodological quality scores are represented in [Table 4]. The AMSTAR score ranged from 9 to 10 out of 11 (maximum score) and was therefore categorized as “high.” All the reviews had a score of 0 for only one of the items: “Was the status of publication (i.e., gray literature) used as an inclusion criterion?.” For Tupyota et al., one examiner considered the score 0 for “Was an 'a priori' design provided?” The inter-examiner reliability scores were 0.95 (range: 0.4–1, CI = 0.88–0.98).
Table 4: The Assessment of Multiple Systematic Reviews

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  Discussion Top


Many oral premedications have been considered to increase the anesthetic efficacy of IANB, NSAIDs being the most popular. The need of the present overview is to define the effect of oral premedication with NSAIDs on the anesthetic success of IANB in patients with irreversible pulpitis by highlighting the conclusive facts through high-quality systematic reviews. Although 12 systematic reviews[10],[11],[12],[13],[30],[31],[32],[33],[34],[35],[36],[37] with or without aeta-analyses were performed defining this problem, only three[13],[30],[31] high-quality systematic reviews considering the inclusion criteria answered the problem appropriately. Among them, two systematic reviews with the help of TSA and direct/indirect network meta-analyses conclusively confirmed the use of NSAIDs as an oral premedication to increase the efficacy of IANB in patients of irreversible pulpitis undergoing endodontic treatment.

The question arises as to why only NSAIDS have been given preference when other analgesics and anti-inflammatory drugs such as steroids, opioids, benzodiazepines, and acetaminophen are available. The clinical trials on dexamethasone and tramadol comparing the effect with placebo are very limited to solve the concerned question.[14],[21] Furthermore, these two clinical trials were on asymptomatic irreversible pulpitis, which does not address the concerning question as studies on symptomatic irreversible pulpitis will give reliable findings. It has already been established that the success rate of IANB for symptomatic and asymptomatic irreversible pulpitis was 64.2% and 86.9%, respectively.[56] Limited literature is available concerning benzodiazipines. Benzodiazipines also prove to have harmful sedative action on patients. Acetaminophen in combination with NSAIDs has a minimal advantage in improving the anesthetic success of IANB, which has been concluded by Pulikkotil et al.[30] In conclusion, the maximum work including low-risk and high-risk clinical trials was on NSAIDs only.

The outcome assessed by all three reviews[13],[30],[31] is chiefly the role of NSAIDs in comparison with placebo in increasing the efficacy of IANB during access opening or root canal instrumentation. Nagendrababu et al.[13] and Pulikkotil et al.[30] specifically mentioned the dose-related effect of NSAIDs on the success of IANB. Pulikkotil et al.[30] specifically compared NSAIDs with other oral premedications by direct and indirect network meta-analyses and finally conclusively prioritized the superior role of NSAIDs in comparison to other drugs. This is attributed to the role of NSAIDs in reducing nociceptor activation by decreasing the levels of inflammatory mediators. The subgroup analysis of the high-quality systematic review by Nagendrababu et al.[13] clearly defined the role of ibuprofen >400 mg, diclofenac 50 mg, and ketorolac on the anesthetic success of IANB through TSA. Role of ibuprofen ≤400 mg is still inconclusive. Furthermore, among NSAIDs, the dose-wise ranking is as follows: ketorolac 10 mg, piroxicam 20 mg, ibuprofen 400 mg, plus acetaminophen 500 mg on the success of IANB. Acelofenac 100 mg, ibuprofen 300 mg, and naproxen 550 mg did not provide any significant effect on anesthetic success of IANB.

Regarding the quality of included reviews, a total of three systematic reviews with meta-analyses were included following the inclusion criteria of this overview.[13],[30],[31] The quality was appraised with the aid of the AMSTAR tool. Since the number of systematic reviews on oral premedication including NSAIDs is more, therefore, it is imperative to evaluate the quality and reliability of the included systematic reviews with meta analyses. Tupyota et al.[31] included only five randomized control trials with a low risk of bias and did not include all the studies[18],[20],[50],[51],[52] for their mentioned search strategy time frame (i.e., April 2013). Thirteen randomized control trials were included by Nagendrababu et al.,[13] out of which eight had a low risk of bias,[14],[16],[17],[47],[48],[49],[51],[53] four with a high risk of bias,[18],[20],[50],[52] and one with unclear risk of bias.[19] Pulikkotil et al.[30] evaluated 14 randomized control trials, eight with low risk of bias,[14],[16],[17],[47],[48],[49],[51],[53] four with high risk of bias,[18],[20],[50],[52] and two with unclear risk of bias.[19],[21]

All three reviews[13],[30],[31] included the studies of asymptomatic irreversible pulpitis, which are limited in number to affect the results.[14],[21] The studies on symptomatic irreversible pulpitis are much more in this group. But if we consider them separately in the steroid group or opioid analgesics group, then the confirmatory results cannot be achieved based on these limited studies with asymptomatic irreversible pulpitis patients. Ideally, studies of asymptomatic irreversible pulpitis should not be part of reviews highlighting the role of any medication on the anesthetic success of IANB in patients with irreversible pulpitis as it may influence the results.

All three systematic reviews possess a high-quality evidence level including meta-analyses. Two reviews[13],[30] performed high-quality meta-analyses by including TSA, direct and indirect network meta-analyses to prove the accuracy and reliability of the work. The present overview has summarized systematically the current evidence on the effect of oral premedication with NSAIDs on the anesthetic success of inferior alveolar nerve block in patients with irreversible pulpitis with high evidence-based results.

Discussing the limitations of other systematic reviews, one review has not defined any particular criteria for evaluating the anesthetic success of IANB.[10] In some reviews, the success criteria are mentioned; however, they have included studies not following the criteria.[10],[11],[12],[35],[37] Some of them did not include placebo as a comparator to the NSAIDs.[33],[34],[35],[36] Two reviews mentioned symptomatic irreversible pulpitis in their inclusion criteria and have included studies with asymptomatic irreversible pulpitis.[32],[34] One review strictly involved NSAIDs as part of the study but included studies in combination with acetaminophen.[10] Hence, these points should be considered while further writing a systematic review on the effect of oral premedication on the anesthetic success of IANB.

Recommendations for further clinical trials

The inclusion criteria should be well defined keeping in mind: (i) the patients/population involved in terms of symptomatic or asymptomatic irreversible pulpitis, (ii) placebo should be one of the comparator groups, (iii) well-defined criteria for accessing the anesthetic success of IANB must be mentioned, (iv) acetaminophen should not be considered a part of studies specifically on NSAIDs, (v) The dose-dependent effect of NSAIDs should be evaluated, (vi) the secondary outcome in the form of any reported side effect of the drug should be considered, (vii) involved clinical trials should possess the low risk of bias by avoiding the confounding factors, (viii) the planned protocol should be registered with a well-defined PICO question, (ix) gray literature should be included as an as a part of search strategy, (x) the quality assessment results of all the clinical trials should be part of the review, and (xi) Sub-group meta-analyses should be considered for the dose-dependent effect of the drug.

The following points can be considered as the strength of the present overview: (i) a properly framed protocol registered in the PROSPERO database, (ii) a thorough literature search to not miss any relevant reviews, (iii) independent literature search and data extraction by two reviewers with any disagreement resolved by the third reviewer Appraising the quality of reviews using AMSTAR. This overview tries to highlight the limitation of other systematic reviews through its exclusion criteria.

Although only three systematic reviews are part of this overview, all of them are of high evidence level with high quality of meta-analyses sufficient to prove the question.

Limitations

The following limitations in the current overview have been pointed out: (i) none of the systematic reviews revealed the adverse effect of the NSAIDs since included randomized control trials did not consider this issue, (ii) more work is required regarding the conclusive statement for subgroup analysis related to the ranking and dose-dependent effect of NSAIDs on the anesthetic success of IANB, and (iii) exclusion of systematic reviews in any language other than English.


  Conclusion Top


With the help of this overview, a lot of dilemmas regarding the use of NSAIDs as oral premedication for the success of IANB can be cleared. In the future, more work is required regarding the conclusive statement for subgroup analysis related to the ranking and dose-dependent effect of NSAIDs on the anesthetic success of IANB in patients with irreversible pulpitis during root canal treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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