A systematic review is a method of study that uses scientific ways to identify and collect quantitative or quantitative findings of all studies related to a question at the highest level required in health research. This type of study helps review evidence, develop guidelines, inform policies, and assess the cost-effectiveness of interventions.¹,² Over the past decade, systematic reviews have grown as critical tools for promoting evidence-based health care and as a type of high-level, low-cost research. However, some found that the quality of the articles was generally poor as a result of the reports and methodological shortcomings.³,⁴ This field has both opportunities and risks: In particular, it creates an environment where researchers can make the best decision based on accurate, concise, credible, and understandable evidence. However, variations in empirical quality and validity can lead to biases or inaccuracies that affect the validity of findings.¹

Successful management of pain during endodontic treatment is essential for both patients and dentists.⁵ Achieving adequate pulp anesthesia is a significant concern for patients with irreversible pulpitis during endodontic treatment.⁶ Practitioners commonly use the inferior alveolar nerve block (IANB) technique to achieve pulp anesthesia in mandibular teeth. Researchers observed that the IANB failure rate was between 43% and 83% in patients with irreversible pulpitis.⁷,⁸,⁹ The researchers have mainly related IANB failure in teeth with irreversible pulpitis to inflammation in the pulp.¹⁰ Inflammation occurs through the production of prostaglandins, which are involved in causing and enhancing pain, from arachidonic acid in cell membranes by cyclooxygenase enzymes.¹⁰,¹¹ The increased sensitization of nociceptors due to inflammation decreases the success of IANB.¹⁰,¹¹,¹² The main focus is on reducing inflammation before delivery of local anesthesia to increase the success of anesthetic drugs. Inflammation is responsible for inappropriate anesthesia because inflammation mediators can stimulate pain fibers even at very low thresholds. It has been suggested that reducing prostaglandin levels may increase the local anesthetic effects.¹³ As a result, several authors have made efforts to prescribe the best drug or combination of medicines before endodontic therapy to reduce inflammation and reduce the mediators that are the leading cause of painful symptoms. However, while some drugs are promising, there is no clinical consensus among authors on the subject through systematic reviews.

With the increase in the number of available systematic reviews, a logical and appropriate next step is to review the existing systematic reviews, allowing the findings of independent studies to be compared and contrasted, thus providing the best evidence needed for practitioners. A review of systematic reviews is carried out under several different names in the scientific literature, including umbrella reviews, an overview of reviews, summaries of systematic reviews, and synthesis of reviews. Irrespective of their name, these reviews have a defining feature in common: A systematic review is a principal and often sole “study type” that is considered for inclusion.¹⁴,¹⁵,¹⁶ The principal reason for conducting an umbrella review is summarizing the evidence from multiple research syntheses.¹⁵ The conduct of an umbrella review may also offer a means for a rapid review of the evidence to address broad and high-quality information about a topic.¹⁶ Umbrella reviews are conducted to comprehensively examine a given topic's available body of knowledge and compare and contrast published systematic reviews' results.¹⁴ Thus, this umbrella review aimed to revise, qualify and summarize the existing body of evidence on the effect of premedication on IANB in patients diagnosed with irreversible pulpitis in molar teeth.

This umbrella review was undertook following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and its protocol is registered in in PROSPERO (CRD42021286004).¹⁷

Review question

The review question was made based on the patient, intervention, comparison, outcome framework.

Does premedication (I) improve the success rate of IANB (O) compared to placebo (C) in adult patients (P) diagnosed with irreversible pulpitis in molar teeth?

Sources and search-line

PubMed (MEDLINE), Scopus, the Web of Science, and the Cochrane Library of systematic reviews were reviewed up to September 15^th, 2021, Considering MeSH terms and synonyms related to IANB (“IANB” OR “mandibular nerve block” OR “IANB”) and related to premedication (“Oral premedication” OR “premedication”) and related to systematic reviews (“systematic review” OR “meta-analysis”) adapted for each database, with no date restrictions, only records published in English were selected. We performed a hand search in the reference lists of selected records. OpenGrey, ProQuest, and WorldCat were searched to obtain grey literature and unpublished reviews.

Eligibility criteria

The included records had to report the anesthetic solution used and the premedication drug to identify any association. The included studies had to clarify the method of checking the proper anesthesia (no response to electric pulp tester (EPT), no pain feeling during access cavity preparation or instrumentation). We excluded network meta-analysis (due to different methodology), literature reviews, critical reviews, letters to the editor, case reports or case series, and observational or clinical studies.

Study selection

Two reviewers (S. B. and N. M) independently evaluated the titles and abstracts of all records. Next full-text copies from studies that met the inclusion criteria or for which there were insufficient data available to make a clear decision possible were retrieved. Two reviewers resolved any disagreements through consensus or discussion with a third expert reviewer (A. K.).

Data extraction

Details of each study (first author's name, date of search, and date of publication), study methods (method of analysis, methodological quality assessment tool (s) used), results (number of studies included, meta-analysis), and study conclusions were extracted by two reviewers (S. B. and N. M.) independently. Any disagreements between authors were resolved through a third author (A. K). When necessary, we contacted corresponding authors to obtain missing (or not specified) data from the included studies via E-mail.

Risk of bias (methodological quality assessment)

AMSTAR 2 approach was used to evaluate the methodological quality of retrieved systematic reviews.¹,² Two reviewers (S. B. and N. M.) independently discussed the AMSTAR 2 [Supplementary Table 1[SUPPORTING:1]] criteria and this instrument's application in the selected studies, defining each parameter of analysis. Any disagreement was resolved by consultation with a third reviewer (A. K.). AMSTAR 2 includes a 16-item checklist covering all of the steps taken during a systematic review and meta-analysis. The following seven domains can critically affect the conclusions (items 2, 7, 9, 11, 13,14 and 15).¹ Based on critical and noncritical domains, AMSTAR 2 calculates the degree of confidence in the results of a review as either critically low, low, moderate, or high.¹

Choice of the best body of evidence

When a premedication was addressed by more than one systematic review with discordance, the Jadad decision algorithm was applied to select the systematic review that provided the best body of evidence according to the currently available studies. The Jadad decision algorithm is designed as an adjunct decision tool to help decision-makers interpret and choose among discordant systematic reviews.¹⁸ It is a sequence of reasoning (comprising questions on the methodology of the studies) used when two or more systematic reviews had discordant conclusions about the same exposure. This decision (choice of the study, or studies, that preset the best methodology and, consequently, the best evidence) is based on differences in the study question, trials included, type of study method selected, quality of assessments, criteria for the selection of primary studies, data extraction methods, data combinations, statistical analysis methods, search strategies, and study selection.

Literature search

Relevant systematic reviews were identified and selected Figure 1. The initial search resulted in 29 reviews, and of these, 9 were removed as they were duplicates. Following title and abstract screening, a total of 16 studies were excluded, because they did not satisfy the inclusion criteria with 4 studies being shortlisted for full-text retrieval. After reading the full text, all 4 systematic reviews were selected for this umbrella review (Nagendrababu et al.,¹⁹ de Geus et al.,²⁰ Shirvani et al.²¹ and Karapina-Kazandag et al.²²).Figure 1

Flow diagram of study selection process.

This umbrella review attempted to identify the best premedication drug for successful local anesthesia in the mandible in adult patients with irreversible pulpitis requiring root canal treatment. Inability to achieve pulpal anesthesia during root canal treatment can increase fear and anxiety in patients. Thus, patient management will be more challenging, prolonging the duration of the appointments and creating concern in the mind of patients about physician competence.²³ In an umbrella review, the results of several systematic reviews are summarized in an overview before combining the data to integrate all relevant information. The goal is to make it more straightforward, reduce uncertainty about decisions, identify gaps in knowledge, and provide a reference publication that contains essential information on the subject.²⁴,²⁵ Therefore, an umbrella review offers the highest level of scientific evidence and is a benchmark for clinical decision-making.

Consequently, we used an umbrella review approach in this study to provide specific and clear recommendations to clinicians on what premedication they should use in addition to local anesthesia for their adult patients presenting with irreversible pulpitis and needing root canal treatment. The authors of the current umbrella review had planned to perform a meta-analysis if the primary outcome of the four included studies revealed a disagreement. However, the systematic review with the best body of evidence¹⁹ as well as the other systematic reviews²⁰,²¹,²² concluded that premedication with 400 mg of ibuprofen significantly improved the success of IANB. As a consequence of the consistent conclusions, we considered that there was no need for a meta-analysis.

Quality of systematic reviews

The quality of two individual systematic reviews included in this umbrella review was categorized as “high.”¹⁹,²⁰ The quality of the other two was classified as “low”²¹,²² when using the AMSTAR 2 tool. AMSTAR has been reported to provide reasonable evidence of validity and reliability and help the reader evaluate the crucial components that a systematic review should include to interpret the results and implications correctly.² AMSTAR 2 has 11 aspects which include a priori design, study selection, and data extraction process, literature search, publication status, study list, characteristics of the included studies, scientific quality of included and evaluated studies, scientific quality of included studies used in formulating conclusions, methods of combining findings, publication bias, and conflict of interest.² AMSTAR's high score for a systematic review does not necessarily mean that the initial randomized clinical trials they included were of high quality. However, it is crucial to perform a qualitative evaluation of the randomized clinical trials included in a systematic review to evaluate the quality of the evidence obtained from a subsequent meta-analysis.

Strengths

We conducted the current umbrella review with a strong methodology because it used three electronic databases to search for and identify relevant systematic reviews. Two independent reviewers participated in the selection of the systematic review and data extraction. This accurate method improves the quality of the review process. Umbrella review only included systematic reviews that included randomized clinical trials to provide the highest level of evidence. In addition, registering a priori protocol in the PROSPERO database improves the methodological quality and reporting of the review, increases transparency, reduces the potential for bias, and helps prevent unwanted duplication of studies.

Limitations

The heterogeneity between the randomized clinical trials included in the systematic reviews is widely one of the limitations of this umbrella review. Study heterogeneity included geographical location, sample size, operator experience, criteria for detecting irreversible pulpitis, the volume of anesthetic solution, vasoconstrictor concentration, and injection rate. Systematic reviews published in languages other than English have been omitted, creating a degree of selection bias.

Inconsistencies at the initial research-level complicate the interpretation in this umbrella review because the outcome criterion used to evaluate the efficacy of premedication alongside local anesthetic solutions in randomized clinical trials varied between studies. In some clinical trials, the efficacy of local anesthesia was assessed by a pulp sensitivity test (cold test or EPT). In contrast, in others, efficacy was requested by the patient to show discomfort/pain using the Visual Analogue Scale during the access cavity preparation or pulp removal. This variation in outcome measures causes uncertainty and confusion in the subsequent systematic review, so physicians are unsure of the best premedication and anesthetic solution to use in the root canal treatment.

Concluding remarks

There is ample evidence that premedication with ibuprofen at a dose of >400 mg is associated with a higher success rate of local anesthesia following IANBs

Financial support and sponsorship

Nil.

Conflicts of interest

The authors of this manuscript declare that they have no conflicts of interest, real or perceived, financial or nonfinancial in this article.