Corticosteroids for managing acute pain subsequent to surgical extraction of mandibular third molars: A systematic review and meta-analysis

Anna Miroshnychenko; Maria Azab; Sara Ibrahim; Yetiani Roldan; Juan Pablo Diaz Martinez; Divyalakshmi Tamilselvan; Leon He; Olivia Urquhart; Francisca Verdugo-Paiva; Malavika Tampi; Deborah E Polk; Paul A Moore; Elliot V Hersh; Romina Brignardello-Petersen; Alonso Carrasco-Labra

doi:10.1016/j.adaj.2023.04.018

. Author manuscript; available in PMC: 2024 Mar 4.

Published in final edited form as: J Am Dent Assoc. 2023 Aug;154(8):727–741.e10. doi: 10.1016/j.adaj.2023.04.018

Corticosteroids for managing acute pain subsequent to surgical extraction of mandibular third molars

A systematic review and meta-analysis

Anna Miroshnychenko ¹, Maria Azab ², Sara Ibrahim ³, Yetiani Roldan ⁴, Juan Pablo Diaz Martinez ⁵, Divyalakshmi Tamilselvan ⁶, Leon He ⁷, Olivia Urquhart ⁸, Francisca Verdugo-Paiva ⁹, Malavika Tampi ¹⁰, Deborah E Polk ¹¹, Paul A Moore ¹², Elliot V Hersh ¹³, Romina Brignardello-Petersen ¹⁴, Alonso Carrasco-Labra ¹⁵

¹Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.

²Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada, when the work described in this article was conducted. She now is a medical student, The Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

³Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.

⁴Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.

⁵Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.

⁶Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.

⁷Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada, when the work described in this article was conducted. He now is a medical student, The Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

⁸Department of Evidence Synthesis and Translation Research, American Dental Association Science and Research Institute, Chicago, IL, when part of the work described in this article was conducted. She now is an instructor, Center for Integrative Global Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA.

⁹Epistemonikos Foundation, Santiago, Chile.

¹⁰Department of Cariology, School of Dentistry, University of Michigan, Ann Arbor, MI.

¹¹Department of Dental Public Health, University of Pittsburgh, Pittsburgh, PA.

¹²Department of Dental Public Health, University of Pittsburgh, Pittsburgh, PA.

¹³Department of Oral Surgery and Pharmacology, University of Pennsylvania, Philadelphia, PA.

¹⁴Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.

¹⁵Department of Evidence Synthesis and Translation Research, American Dental Association Science and Research Institute, when part of the work described in this article was conducted. He now is an associate professor, Center for Integrative Global Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA.

^✉

Address correspondence to Dr. Carrasco-Labra, Center for Integrative Global Oral Health, School of Dental Medicine, University of Pennsylvania, 240 S 40th St, 3rd Floor E, Philadelphia, PA 19104, carrascl@upenn.edu.

Roles

Anna Miroshnychenko: MSc, PhD student

Maria Azab: BHSc, bachelor of health sciences student

Sara Ibrahim: BHSc, master’s student

Yetiani Roldan: MD, master’s student

Juan Pablo Diaz Martinez: MSc, research assistant

Divyalakshmi Tamilselvan: BHSc, bachelor of health sciences student

Leon He: BHSc, bachelor of health sciences student

Olivia Urquhart: MPH, senior research associate

Francisca Verdugo-Paiva: DDS, MSc, chief scientific innovation officer

Malavika Tampi: MPH, adjunct professor

Deborah E Polk: PhD, assistant professor

Paul A Moore: DMD, PhD, MPH, professor emeritus

Elliot V Hersh: DMD, MS, PhD, professor

Romina Brignardello-Petersen: DDS, MSc, PhD, assistant professor

Alonso Carrasco-Labra: DDS, MSc, PhD, senior director

PMCID: PMC10910594 NIHMSID: NIHMS1962454 PMID: 37500235

Abstract

Background.

Corticosteroids are used to manage pain after surgical tooth extractions. The authors assessed the effect of corticosteroids on acute postoperative pain in patients undergoing surgical tooth extractions of mandibular third molars.

Types of Studies Reviewed.

The authors conducted a systematic review and meta-analysis. The authors searched the Epistemonikos database, including MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and the US clinical trials registry (ClinicalTrials.gov) from inception until April 2023. Pairs of reviewers independently screened titles and abstracts, then full texts of trials were identified as potentially eligible. After duplicate data abstraction, the authors conducted random-effects meta-analyses. Risk of bias was assessed using Version 2 of the Cochrane Risk of Bias tool and certainty of the evidence was determined using the Grading of Recommendations Assessment, Development and Evaluation approach.

Results.

Forty randomized controlled trials proved eligible. The evidence suggested that corticosteroids compared with a placebo provided a trivial reduction in pain intensity measured 6 hours (mean difference, 8.79 points lower; 95% CI, 14.8 to 2.77 points lower; low certainty) and 24 hours after surgical tooth extraction (mean difference, 8.89 points lower; 95% CI, 10.71 to 7.06 points lower; very low certainty). The authors found no important difference between corticosteroids and a placebo with regard to incidence of postoperative infection (risk difference, 0%; 95% CI, −1% to 1%; low certainty) and alveolar osteitis (risk difference, 0%; 95% CI, −3% to 4%; very low certainty).

Practical Implications.

Low and very low certainty evidence suggests that there is a trivial difference regarding postoperative pain intensity and adverse effects of corticosteroids administered orally, submucosally, or intramuscularly compared with a placebo in patients undergoing third-molar extractions.

Keywords: Corticosteroids, surgical tooth extraction, third molars, postoperative pain, evidence-based dentistry

Surgical removal of impacted mandibular third molars is 1 of the most frequently performed surgical interventions in dental surgery, with more than 10 million teeth extracted per year.¹ The most common complications, including pain, swelling, and trismus, can severely affect a patient’s quality of life during the immediate postoperative period. Analgesics and anti-inflammatory drugs prescribed postoperatively should relieve pain, reduce swelling and trismus, and improve healing without undesirable adverse effects. Therefore, medications that exert both analgesic and anti-inflammatory effects, such as corticosteroids, could be used for the management of postoperative discomfort.

Corticosteroids can be divided into 2 major groups, that is, glucocorticoids and mineralocorticoids. Glucocorticoids are used for the management of postoperative complications after surgical tooth extraction because of their substantial anti-inflammatory effects.² The term corticosteroids will be used to represent glucocorticoids in our review.

Corticosteroids are classified according to their duration of action and relative anti-inflammatory potency compared with hydrocortisone, a reference standard with a potency of 1. The higher the relative potency anti-inflammatory score, the higher the corticosteroid’s anti-inflammatory potency. Short-acting glucocorticoids include cortisol and cortisone, with a duration of action of fewer than 12 hours and anti-inflammatory potency of 1.³ Intermediate-acting corticosteroids include prednisone and prednisolone, with an anti-inflammatory potency of 4, and 6-methylprednisolone and triamcinolone, which both have an anti-inflammatory potency of 5. Intermediate corticosteroids have a duration of action of 12 through 36 hours. The long-acting glucocorticoids include dexamethasone, with a duration of action of more than 36 hours and anti-inflammatory potency of 25.³ The administration of corticosteroids in dentistry typically varies among oral, intramuscular, and submucosal routes.

Available systematic reviews (SRs) to inform the effect of corticosteroids for managing postoperative acute pain consecutive to surgical tooth extractions have several limitations. Almost all were published before 2018,^4–7 with only 1 published in 2020.⁸ They did not use the Grading of Recommendations Assessment, Development and Evaluation (GRADE)⁹ approach to assess the certainty of the evidence—an essential component of SRs and a key step to inform the formulation of guideline recommendations—and they applied suboptimal methods to synthesize pain-related outcomes.

The purpose of our SR was to determine the effect of corticosteroids administered orally, submucosally, or intramuscularly on the management of pain subsequent to surgical tooth extraction, including impacted mandibular third-molar extractions. Our review informed the clinical questions posed by the forthcoming evidence-based clinical practice guideline for the pharmacologic management of acute dental pain consecutive to tooth extractions (A. Carrasco-Labra D.E. Polk, O. Urquhart, and colleagues, unpublished data, 2023). This review and associated clinical practice guidelines were led by the American Dental Association Science and Research Institute, the School of Dental Medicine at the University of Pittsburgh, the Center for Integrative Global Oral Health at the University of Pennsylvania, and a guideline panel including primary care dentists, oral and maxillofacial surgeons, public health practitioners, pharmacoepidemiologists, biostatisticians, and health research methodologists, among others.

METHODS

This article follows the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement¹⁰ (eTable 1, available online at the end of this article). We also followed established methodological considerations defined for evidence synthesis and guideline development, used eligibility criteria determined per the recommendation questions that the guideline panel proposed, and used information outlined in the National Academy of Medicine’s Framing Opioid Prescribing Guidelines for Acute Pain: Developing the Evidence.¹¹

Eligibility criteria

We included randomized controlled trials (RCTs) that compared the effect of corticosteroids administered orally, submucosally, or intramuscularly at any dose with that of a placebo in adolescent, adult, or older adult participants undergoing surgical (that is, extraction of a tooth with the need of a flap and osteotomy) third-molar extraction, regardless of the language of publication. We included the following continuous outcomes: pain intensity at 6 hours, pain at 24 hours, total pain relief at 6 hours, and global efficacy rating at 6 hours. We included the following dichotomous outcome: adverse effects (for example, postoperative surgical site infection, alveolar osteitis, mood alteration, and gastrointestinal [GI] adverse effect at any time). We excluded studies that administered corticosteroids intravenously and studies that only reported outcomes associated with the management of inflammatory complications (that is, trismus, facial swelling, or infection).

Search methods to identify and select studies

We performed the evidence search in 2 steps. First, we conducted searches in the Epistemonikos database, a comprehensive mate-search engine and updated source of relevant SRs and primary studies to inform health decision making (Appendix, available online at the end of this article). Using artificial intelligence technology, Epistemonikos periodically screens across the following databases: Cochrane Database of Systematic Reviews, PubMed, MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Latin American and Caribbean Health Sciences Literature, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database, Campbell Collection online library, Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports, Evidence for Policy and Practice Centre Evidence Library, and the US clinical trials registry (ClinicalTrials.gov).¹² Our search strategy included a combination of free and controlled key words. These terms include specific key words to represent the concepts of surgical extraction, third molars, and corticosteroids (Appendix, available online at the end of this article).

In addition, we used the Living Overview of Evidence (L·OVE) platform (Epistemonikos Foundation), which maps the question of interest to a repository maintained through additional searches on PubMed, Embase, and Cochrane Central Register of Controlled Trials. We searched L·OVE for third-molar–related literature without restriction according to study design, language, or publication status.¹³ The search covered the period from the inception date of each database through April 2023 and had no language restrictions. The results of the searches in each source were deduplicated by means of an algorithm that compares unique identifiers (that is, database identi-fication, digital object identifier, and trial registry identification) and citation details (that is, author names, journal, year of publication, volume, number, pages, article title, and article abstract).

Pairs of reviewers (A.M., M.A., Y.R., J.P.D.M., D.T., L.H., F.V.-P.) independently evaluated the titles, abstracts, and full text of potentially eligible studies across all databases. When eligibility consensus was elusive, a third reviewer served as arbiter (R.B.-P., A.C.-L.).

Data collection

After training and calibration exercises, pairs of reviewers independently extracted data for each eligible trial using a standardized, pilot-tested data extraction form. We collected information on trial characteristics (for example, intervention, comparison, and co-interventions), patient characteristics (for example, age, sex, country, and type of extraction), and outcomes of interest. Reviewers resolved discrepancies by means of discussion, and, when necessary, a third reviewer served as arbiter.

Risk of bias in studies

After training and calibration exercises, pairs of reviewers used Version 2 of the Cochrane Risk of Bias tool for each eligible trial and outcome to assess risk of bias in RCTs, rating trials as being at low risk of bias, probably at low risk of bias, probably at high risk of bias, or at high risk of bias across the domains of bias arising from the randomization process, bias due to deviations from the intended intervention, bias due to missing data, bias due to measurement of the outcome, and bias in selection of the reported results.¹⁴ We rated trials as high risk of bias overall if 1 or more domains were rated as probably high risk of bias or at high risk of bias, and we rated trials as low risk of bias overall if all domains were rated as probably at low risk of bias or at low risk of bias. Reviewers resolved discrepancies by means of discussion and, when necessary, a third reviewer served as arbiter.

Data synthesis

For dichotomous outcomes, we summarized the effect of interventions using odds ratios. When the incidence of the outcome was low across studies (that is, there were no events in several study groups), we used the risk difference. For continuous outcomes, we used the mean difference. When studies reported the same outcome using a scale with a different range, we converted the data to the most reported scale before conducting analyses. In addition, we calculated 95% CIs around all of these estimates and created forest plots (in which the black diamond represents the pooled estimate across studies). In instances when the SD was not reported, we calculated SDs using SE, CIs, means, and sample sizes. In rare cases when none of these statistics were reported, we imputed the SD by means of averaging the SDs of 3 studies with similar means. We conducted random-effects meta-analyses using Review Manager (Cochrane) software.

Certainty of the evidence

We assessed the certainty of the evidence using the GRADE approach.⁹ Two methodologists (F.V.-P., A.C.-L.) formally trained in using GRADE rated each domain for each comparison and outcome independently, resolving discrepancies by means of discussion. We rated the certainty as high, moderate, low, or very low, taking into consideration risk of bias, inconsistency, indirectness, publication bias, and imprecision. We used a minimally contextualized approach with a null effect threshold to rate the certainty that there is a benefit or harm.¹⁵ When the point estimate was close to the null effect, we rated our certainty as having a trivial effect (that is, no important difference) using a threshold of 10% of the baseline risk of dichotomous outcomes and 10% of the scale range for continuous outcomes.¹⁶ For dichotomous outcomes, we calculated absolute estimates of effect using the mean baseline risk across trials. We created GRADE summary of findings tables using GRADEpro software (McMaster University and Evidence Prime).

Subgroup analyses

We performed 2 subgroup analyses to determine the extent to which treatment effects vary according to the type of corticosteroid (for example, dexamethasone, methylprednisolone, prednisolone, and triamcinolone acetonide) and routes of administration (oral, intramuscular, submucosal) compared with a placebo.

RESULTS

The search of the Epistemonikos database initially identified a total of 44 search results. Titles and abstracts of all SRs were screened for our inclusion criteria, and 19 SRs proved relevant. These SRs included a total of 79 RCTs (reported in 81 references) comparing the use of corticosteroids with a placebo for patients undergoing surgical third-molar extractions. All identified RCTs were entered into our database. The following link provides access to the interactive version of the matrix of evidence that we built, as described above (corticosteroids vs a placebo for patients undergoing third-molar extractions: http://www.epistemonikos.org/matrixes/60cfb16e7aaac86eee79456c).

After removal of duplicates, the search in the L·OVE platform for “corticosteroids” and “third molar” yielded 240 records to screen at the title and abstract stage. Then, 103 of those records were potentially eligible, and their full texts were evaluated. Finally, 40 RCTs (64 references) were included.^17–56 The complete study selection process, including the reasons for excluding studies at the time of the full-text review, is summarized in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart (Figure 1).

Figure 1. — Study identification and selection flowchart.

Characteristics of included studies

Most RCTs were parallel group in design (88%), with the number of participants ranging from 30 through 450. Mean (SD) age of participants across studies ranged from 18 (not reported) to 31.42 (11.76) years. All populations across included studies underwent surgical extraction of the impacted third molars (Table 1).

Table 1.

Characteristics of the included studies examining corticosteroids.

STUDY^*	STUDY DESIGN	COUNTRY	PARTICIPANTS RANDOMIZED, NO.	AGE, Y	SEX, FEMALE, %	TYPE OF EXTRACTION	INTERVENTIONS
ElHag and Colleagues,²⁸ 1985	Parallel group	England	70	Mean (SD), 23.5 (NR^†)	51.42	Surgical tooth extraction (impacted third molar)	10 mg of dexamethasone 1 h preoperatively and 10–18 h postoperatively (intramuscular), no corticosteroid treatment (placebo)
Pedersen and Colleagues,⁴⁷ 1985	Split mouth	Denmark	66	Mean (SD), 22 (NR)	56.66	Surgical tooth extraction (impacted third molar)	4 mg of dexamethasone (intramuscular), no treatment (placebo)
Schmelzeisen and Colleagues,⁵¹ 1993	Split mouth	Germany	80	Mean (SD), 18 (NR)	45	Surgical tooth extraction (impacted third molar)	6 mg of dexamethasone 12 h preoperatively and 12 h postoperatively (oral), no treatment (placebo)
Buyukkurt and Colleagues,²³ 2006	Parallel group	Turkey	30	Range, 18–36	44.44	Surgical tooth extraction (impacted third molar)	25 mg of prednisolone postoperatively (intramuscular), no treatment (placebo)
Grossi and Colleagues,³³ 2007A	Parallel group	Italy	61	Mean (SD), 27.7 (6.5)	45.9	Surgical tooth extraction (impacted third molar)	4 mg of dexamethasone (submucosal), no treatment (placebo)
Grossi and Colleagues,³³ 2007B	Parallel group	Italy	61	Mean (SD), 27.7 (6.5)	45.9	Surgical tooth extraction (impacted third molar)	8 mg of dexamethasone (submucosal), no treatment (placebo)
Vegas-Bustamante and Colleagues,⁵⁵ 2008	Parallel group	Spain	80	Mean (SD), 25 (5)	46	Surgical tooth extraction (impacted third molar)	40 mg of methylprednisolone (intramuscular), no treatment
Kang and Colleagues,³⁶ 2010A	Parallel group	Republic of Korea	450	Range, 20–30	NR	Surgical tooth extraction (impacted third molar)	10 mg of prednisolone (oral), no treatment (placebo)
Kang and Colleagues,³⁶ 2010B	Parallel group	Republic of Korea	450	Range, 20–30	NR	Surgical tooth extraction (impacted third molar)	20 mg of prednisolone (oral), no treatment (placebo)
Tiigimae and Colleagues,⁵⁴ 2010	Parallel group	Estonia	78	Mean (SD) 30.57 (13.73)	73	Surgical tooth extraction (impacted third molar)	120 mg of etorikoxib preoperatively and 30 mg of prednisolone immediately postoperatively (oral), 120 mg of etorikoxib preoperatively
Antunes and Colleagues,¹⁸ 2011A	Parallel group	Brazil	60	Mean (SD), 21 (5.4)	38.4	Surgical tooth extraction (impacted third molar)	8 mg of dexamethasone (intramuscular), no treatment (placebo)
Antunes and Colleagues¹⁸ 2011B	Parallel group	Brazil	60	Mean (SD), 21 (5.4)	38.4	Surgical tooth extraction (impacted third molar)	8 mg of dexamethasone (oral), no treatment (placebo)
Deo and Colleagues,²⁵ 2011	Parallel group	India	30	Mean (SD), 24.93 (NR)	40	Surgical tooth extraction (impacted third molar)	8 mg of dexamethasone (submucosal), no treatment (placebo)
Majid and Colleagues,⁴¹ 2011A	Parallel group	Iraq	33	Mean (SD), 26.9 (6.1)	51.51	Surgical tooth extraction (impacted third molar)	4 mg of dexamethasone (intramuscular), no treatment (placebo)
Majid and Colleagues,⁴¹ 2011B	Parallel group	Iraq	33	Mean (SD), 26.9 (6.1)	51.51	Surgical tooth extraction (impacted third molar)	4 mg of dexamethasone (submucosal), no treatment (placebo)
Majid and Colleagues,⁴² 2011A	Parallel group	Iraq	30	Mean (SD), 26.7 (6.3)	46.66	Surgical tooth extraction (impacted third molar)	4 mg of dexamethasone (intramuscular), no treatment (placebo)
Majid and Colleagues,⁴² 2011B	Parallel group	Iraq	30	Mean (SD), 26.7 (6.3)	46.66	Surgical tooth extraction (impacted third molar)	4 mg of dexamethasone (submucosal), no treatment (placebo)
Bauer and Colleagues,²⁰ 2012	Parallel group	Brazil	54	Mean (SD), 22 (3.6)	68.09	Surgical tooth extraction (impacted third molar)	600 mg of ibuprofen, 8 mg of dexamethasone (oral), no corticosteroid treatment (placebo)
Bortoluzzi and Colleagues,²² 2013A	Parallel group	Brazil	50	Mean (SD), 22.5 (NR)	NR	Surgical tooth extraction (impacted third molar)	8 mg of dexamethasone and 2 g of amoxicillin, 2 g of amoxicillin (oral)
Bortoluzzi and Colleagues,²² 2013B	Parallel group	Brazil	50	Mean (SD), 22.5 (NR)	NR	Surgical tooth extraction (impacted third molar)	8 mg of dexamethasone (oral), no treatment (placebo)
Majid and Colleagues,⁴³ 2013A	Parallel group	Iraq	47	Mean (SD), 25.69 (5.53)	57.45	Surgical tooth extraction (impacted third molar)	4 mg of dexamethasone (intramuscular), no treatment (placebo)
Majid and Colleagues,⁴³ 2013B	Parallel group	Iraq	47	Mean (SD), 25.69 (5.53)	57.45	Surgical tooth extraction (impacted third molar)	4 mg of dexamethasone (submucosal), no treatment (placebo)
Majid and Colleagues,⁴³ 2013C	Parallel group	Iraq	47	Mean (SD), 25.69 (5.53)	57.45	Surgical tooth extraction (impacted third molar)	1 mg of dexamethasone (oral), no treatment (placebo)
Nair and Colleagues,⁴⁵ 2013	Parallel group	India	100	NR	NR	Surgical tooth extraction (impacted third molar)	4 mg of dexamethasone (submucosal), no treatment (placebo)
Simone and Colleagues,⁵³ 2013	Parallel group	Brazil	34	NR	70.59	Surgical tooth extraction (impacted third molar)	8 mg of dexamethasone (oral), no treatment (placebo)
Bhargava and Colleagues,²¹ 2014A	Parallel group	India	40	NR	NR	Surgical tooth extraction (impacted third molar)	4 mg/mL of dexamethasone (submucosal), no treatment (placebo)
Bhargava and Colleagues,²¹ 2014B	Parallel group	India	40	NA	NA	Surgical tooth extraction (impacted third molar)	4 mg/mL of dexamethasone (intramuscular), no treatment (placebo)
Bhargava and Colleagues,²¹ 2014C	Parallel group	India	40	NA	NA	Surgical tooth extraction (impacted third molar)	4 mg of dexamethasone (oral), no treatment (placebo)
Zerener and Colleagues,⁵⁶ 2015A	Parallel group	Turkey	78	Mean (SD), 22.6 (6.3)	48.72	Surgical tooth extraction (impacted third molar)	4 mg of dexamethasone (submucosal), no treatment (placebo)
Zerener and Colleagues,⁵⁶ 2015B	Parallel group	Turkey	78	Mean (SD), 22.6 (6.3)	48.72	Surgical tooth extraction (impacted third molar)	4 mg of triamcinolone acetonide (submucosal), no treatment (placebo)
Deo and Colleagues,²⁶ 2016A	Parallel group	Nepal	40	Mean (SD), 24.93 (NR)	36.67	Surgical tooth extraction (impacted third molar)	2 mL of 4 mg/mL of dexamethasone (submucosal), no treatment (placebo)
Deo and Colleagues,²⁷ 2016B	Parallel group	Nepal	40	Range, 20–41	NR	Surgical tooth extraction (impacted third molar)	2 mL of 4 mg/mL of dexamethasone (submucosal), no treatment (placebo)
Ibikunle and Colleagues,³⁴ 2016A	Parallel group	Nigeria	191	Mean (SD), 28.1 (7.4)	62.9	Surgical tooth extraction (impacted third molar)	40 mg of prednisolone (oral), no treatment (placebo)
Ibikunle and Colleagues,³⁴ 2016B	Parallel group	Nigeria	191	Mean (SD), 28.1 (7.4)	62.9	Surgical tooth extraction (impacted third molar)	40 mg of prednisolone (submucosal), no treatment (placebo)
Prashar and Colleagues,⁴⁸ 2016	Parallel group	India	30	Mean (SD), 26.5 (NR)	NR	Surgical tooth extraction (impacted third molar)	8 mg of methylprednisolone and 50 mg of diclofenac (oral), 50 mg of diclofenac
Saravanan and Colleagues,⁵⁰ 2016A	Parallel groups	India	60	NR	NR	Surgical tooth extraction (impacted third molar)	4 mg of dexamethasone (intramuscular), no treatment (placebo)
Saravanan and Colleagues,⁵⁰ 2016B	Parallel groups	India	60	NR	NR	Surgical tooth extraction (impacted third molar)	4 mg of dexamethasone (submucosal), no treatment (placebo)
Ghensi and Colleagues,²⁹ 2017A	Parallel group	Italy	80	Mean (SD), 27 (7.1)	46.25	Surgical tooth extraction (impacted third molar)	4 mg of dexamethasone (submucosal), no treatment (placebo)
Ghensi and Colleagues,²⁹ 2017B	Parallel group	Italy	80	Mean (SD), 27 (7.1)	46.25	Surgical tooth extraction (impacted third molar)	4 mg of dexamethasone and 40 mg of bromelain (submucosal), 40 mg of bromelain
Gopinath and Colleagues,³¹ 2017	Parallel group	India	80	NR	NR	Surgical tooth extraction (impacted third molar)	4 mg of dexamethasone (submucosal), no treatment (placebo)
Gozali and Colleagues,³² 2017	Split mouth	Thailand	96	Range, 18–30	60.42	Surgical tooth extraction (impacted third molar)	8 mg of dexamethasone (submucosal), no treatment (placebo)
Khalida and Colleagues,³⁷ 2017	Parallel group	Pakistan	60	Mean (SD), 28.77 (7.04)	36.67	Surgical tooth extraction (impacted third molar)	4 mg/mL of dexamethasone (submucosal), no treatment (placebo)
Lim and Colleagues,⁴⁰ 2017A	Parallel group	Malaysia	65	Mean (SD), 25 (4)	81.67	Surgical tooth extraction (impacted third molar)	4 mg/mL of dexamethasone (submucosal), no treatment (placebo)
Lim and Colleagues,⁴⁰ 2017B	Parallel group	Malaysia	65	Mean (SD), 25 (4)	81.67	Surgical tooth extraction (impacted third molar)	40 mg of methylprednisolone (submucosal), no treatment (placebo)
Mojsa and Colleagues,⁴⁴ 2017A	Parallel group	Poland	60	Range, 18–42	64.44	Surgical tooth extraction (impacted third molar)	4 mg/mL of dexamethasone preoperatively (submucosal), no treatment (placebo)
Mojsa and Colleagues,⁴⁴ 2017B	Parallel group	Poland	60	Range, 18–42	64.44	Surgical tooth extraction (impacted third molar)	4 mg/mL of dexamethasone postoperatively (submucosal), no treatment (placebo)
Selimovic and Colleagues,⁵² 2017	Parallel group	Bosnia and Herzegovina	40	Range, 18–45	NR	Surgical tooth extraction (impacted third molar)	32 mg of methylprednisolone and 15 mg of meloxicam (oral), 15 mg of meloxicam
Afkan and Colleagues,¹⁷ 2018A	Parallel group	Iran	75	Mean (SD), 28 (NR)	NR	Surgical tooth extraction (impacted third molar)	2 mg of dexamethasone preoperatively and postoperatively (oral), no treatment (placebo)
Afkan and Colleagues,¹⁷ 2018B	Parallel group	Iran	75	Mean (SD), 28 (NR)	NR	Surgical tooth extraction (impacted third molar)	2 mg of dexamethasone (oral), no treatment (placebo)
Chugh and colleagues,²⁴ 2018A	Parallel group	India	60	Mean (SD), 29.79 (8.37)	36.67	Surgical tooth extraction (impacted third molar)	8 mg of dexamethasone (submucosal), no treatment (placebo)
Chugh and colleagues,²⁴ 2018B	Parallel group	India	60	Mean (SD), 29.79 (8.37)	36.67	Surgical tooth extraction (impacted third molar)	40 mg of methylprednisolone (submucosal), no treatment (placebo)
Atalay and colleagues,¹⁹ 2020A	Parallel group	Turkey	60	Mean (SD), 25.18 (5.26)	46.67	Surgical tooth extraction (impacted third molar)	1 mL of 4 mg/mL of dexamethasone solution (submucosal), no treatment (placebo)
Atalay and colleagues,¹⁹ 2020B	Parallel group	Turkey	60	Mean (SD), 25.18 (5.26)	46.67	Surgical tooth extraction (impacted third molar)	2 mL of 8 mg/mL of examethasone solution (submucosal), no treatment (placebo)
Larsen and Colleagues,³⁸ 2020A	Split mouth	Denmark	104	Mean (SD), 25.92 (5.99)	69.23	Surgical tooth extraction (impacted third molar)	20 mg of methylprednisolone (intramuscular), no treatment (placebo)
Larsen and Colleagues,³⁸ 2020B	Split mouth	Denmark	104	Mean (SD), 25.92 (5.99)	69.23	Surgical tooth extraction (impacted third molar)	30 mg of methylprednisolone (intramuscular), no treatment (placebo)
Larsen and Colleagues,³⁸ 2020C	Split mouth	Denmark	104	Mean (SD), 25.92 (5.99)	69.23	Surgical tooth extraction (impacted third molar)	40 mg of methylprednisolone (intramuscular), no treatment (placebo)
Pansard and Colleagues,⁴⁶ 2020	Parallel group	Brazil	114	Mean (SD), 31.43 (11.76)	65.59	Surgical tooth extraction (impacted third molar)	8 mg of dexamethasone (oral), no treatment (placebo)
Sahu and Colleagues,⁴⁹ 2020	Parallel group	India	40	Range, 18–60	NR	Surgical tooth extraction (impacted third molar)	4 mg/mL of dexamethasone (submucosal), no treatment (placebo)
Gholami and Colleagues,³⁰ 2021A	Parallel group	Iran	60	Mean (SD), 26.83 (4.19)	51.67	Surgical tooth extraction (impacted third molar)	40 mg of methylprednisolone (intramuscular, masseter), no treatment (placebo)
Gholami and Colleagues,³⁰ 2021B	Parallel group	Iran	60	Mean (SD), 26.83 (4.19)	51.67	Surgical tooth extraction (impacted third molar)	40 mg of methylprednisolone (intramuscular, gluteal), no treatment (placebo)
Imon and Colleagues,³⁵ 2021	Parallel group	Bangladesh	294	Mean (SD), 25 (NR)	44.9	Surgical tooth extraction (impacted third molar)	Dexamethasone tapering dose (oral), no treatment (placebo)
Larsen and Colleagues,³⁹ 2021A	Split mouth	Denmark	104	Mean (SD), 25.92 (5.99)	69.23	Surgical tooth extraction (impacted third molar)	20 mg of methylprednisolone (intramuscular), no treatment (placebo)
Larsen and Colleagues,³⁹ 2021B	Split mouth	Denmark	104	Mean (SD), 25.92 (5.99)	69.23	Surgical tooth extraction (impacted third molar)	30 mg of methylprednisolone (intramuscular), no treatment (placebo)
Larsen and Colleagues,³⁹ 2021C	Split mouth	Denmark	104	Mean (SD), 25.92 (5.99)	69.23	Surgical tooth extraction (impacted third molar)	40 mg of methylprednisolone (intramuscular), no treatment (placebo)

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A, B, and C represent different interventions within the same study.

^†

NR: Not reported.

Risk of bias in included studies

Randomization, deviations from the intended intervention, and measurement of outcomes were the risk of bias domains judged as high or probably high risk of bias most frequently across the included studies (eTable 2, available online at the end of this article).

Subgroup analyses

The various types of corticosteroids identified in this review included dexamethasone, methylprednisolone, prednisolone, and triamcinolone acetonide. The route of administration varied among oral, intramuscular, and submucosal. We did not find evidence of a subgroup effect for the comparison of each specific corticosteroid with a placebo (Figures 2–4). Similarly, we did not find compelling evidence of a subgroup effect for the comparison of corticosteroids with a placebo based on administration modes (Figures 3 and 4). Any minor quantitative differences observed across analyses were not clinically significant.

Figure 2. — Corticosteroids vs a placebo for the outcome of pain at 6 hours (corticosteroid type). A and B represent different interventions within the same study.

Figure 4. — Corticosteroids vs a placebo for the outcome of pain at 24 hours (corticosteroid type and route of administration). A, B, and C represent different interventions within the same study.

Figure 3. — Corticosteroids vs a placebo for the outcome of pain at 6 hours (route of administration). A and B represent different interventions within the same study.

Outcome measures

Corticosteroids Compared With a Placebo (No Treatment With Corticosteroids)

Postoperative pain

Seven RCTs, including 396 participants, assessed pain using a visual analog scale ranging from 0 (no pain) through 100 (worst pain imaginable) at 6 hours.^{17,20,22,23,44,53,55} The results suggested that there may be a trivial benefit of corticosteroids compared with a placebo in terms of pain intensity measured 6 hours postoperatively (mean difference, 8.79 points lower; 95% CI, 14.8 to 2.77 points lower; low certainty) (Table 2, Figure 2). Twenty-three RCTs, including 1,555 participants, assessed pain using a visual analog scale ranging from 0 (no pain) through 100 (worst pain imaginable) at 24 hours.^{18,20–22,24–26,30,32,34,36,39–44,48–50,53,55,56} Very low certainty evidence suggested that there may be a trivial difference between corticosteroids and a placebo in terms of pain intensity measured 24 hours postoperatively (mean difference, 8.89 points lower; 95% CI 10.71 to 7.06 points lower; very low certainty) (Table 2, Figure 4).

Table 2.

Corticosteroids vs a placebo (no treatment with corticosteroids) for acute dental pain.

OUTCOME	RELATIVE EFFECT (95% CI)^*	ANTICIPATED ABSOLUTE EFFECTS			CERTAINTY^†	WHAT HAPPENS
OUTCOME	RELATIVE EFFECT (95% CI)^*	With No Treatment (Placebo)	With Corticosteroids	Difference (95% CI)	CERTAINTY^†	WHAT HAPPENS
Pain
Assessed with visual analog scale ranging from 0 (no pain) through 100 (worst pain) Follow-up: 6 h No. of participants: 396 (7 RCTs^§)	–^‡	Median pain, 32.43 points	–	Mean difference 8.79 points lower (14.8 to 2.77 points lower)	Low^¶,#	There may be a trivial benefit of corticosteroids compared with no treatment (placebo) in terms of pain measured 6 h postoperatively.
Assessed with visual analog scale ranging from 0 (no pain) through 100 (worst pain) Follow-up: 24 h No. of participants: 1,555 (23 RCTs)	–	Median pain, 26.06 points	–	Mean difference 8.89 points lower (10.71 to 7.06 points lower)	Very low^**^{,††,‡‡}	There is very low certainty evidence regarding the difference between corticosteroids and no treatment (placebo) in terms of pain measured 24 h postoperatively.
Adverse Effect
Postoperative infection Assessed with proportion of patients experiencing postoperative infection Follow-up: any time No. of participants: 1,630(21 RCTs)	Not estimable	1.3%	2.4%	0% fewer (1% fewer to 1% more)	Low^§§,¶¶	There may be no difference between corticosteroids and no treatment (placebo) with regard to incidence of postoperative infection.
Alveolar osteitis Assessed with proportion of patients experiencing alveolar osteitis Follow-up: any time No. of participants: 410 (8 RCTs)	Not estimable	1.2%	0.8%	0% fewer (3% fewer to 4% more)	Very low^§§,##	There is very low certainty evidence regarding the difference between corticosteroids and no treatment (placebo) in terms of incidence of alveolar osteitis.
Gastrointestinal Assessed with proportion of patients experiencing nausea/vomiting Follow-up: any time No. of participants: 120 (3 RCTs)	Not estimable	21.4%	7.8%	19% fewer (54% fewer to 16% more)	Very low^***^{,†††,‡‡‡}	There is very low certainty evidence regarding the difference between corticosteroids and no treatment (placebo) in terms of incidence of nausea/vomiting.
Total Pain Relief at 6 h, Not Measured	–	–	–	–	–	–
Global Efficacy Rating at 6 h, Not Measured	–	–	–	–	–	–
Mood Alteration, Not Measured	–	–	–	–	–	–

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The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

^†

GRADE Working Group grades of evidence: High certainty: very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

^‡

–: No data were available for the outcome.

^§

RCT: Randomized controlled trial.

^¶

Four studies were at a high risk of reporting bias as they did not provide measures of variability. Three studies were at either a high or probably high risk of attrition bias due to missing outcome data. Therefore, the authors rated down 1 level due to risk of bias.

Using a threshold of 10 points (based on 10% of the scale range), the lower bound of the CI suggests an important difference favoring corticosteroids and the upper bound suggests a trivial difference favoring corticosteroids. Therefore, the authors rated down 1 level due to imprecision.

^**

Several studies were probably at a high risk of bias arising from the randomization process because there was no mention of allocation concealment and the health care providers were not blinded or it was unclear whether they were blinded. Several studies were also at a high risk of performance and detection bias due to a lack of blinding of participants (outcome assessors). In addition, some studies were at a high risk of reporting bias, as they did not report measures of variability. Therefore, the authors rated down 1 level due to risk of bias.

^††

There is high statistical heterogeneity (I² = 91%; P < .00001) and the effect estimates of some studies are importantly different from each other. Therefore, the authors rated down 1 level due to inconsistency.

^‡‡

^§§

Several studies were probably at a high risk of bias arising from the randomization process because there was no mention of allocation concealment and the health care providers were not blinded or it was unclear whether they were blinded. Several studies were also at a high risk of bias due to a lack of blinding of participants. Therefore, the authors rated down 1 level due to risk of bias.

^¶¶

Given the very low event rate, the optimal information size for this outcome was not met. Therefore, the authors rated down 1 level due to imprecision.

^##

Using a threshold of 0.12% (based on 10% of the baseline risk, that is, the risk with a placebo), the lower bound of the CI suggests an important difference favoring corticosteroids and the upper bound suggests an important difference favoring no treatment (placebo). Therefore, the authors rated down 2 levels due to imprecision.

^***

Two studies were at a high risk of attrition bias due to missing outcome data. Two studies were at a high or probably high risk of detection bias as participants were not blinded. One of these studies also had concerns regarding reporting bias as well as the randomization process, as it did not mention allocation concealment and it was unclear whether health care providers were blinded. Therefore, the authors rated down 1 level due to risk of bias.

^†††

There is high statistical heterogeneity (I² = 90%; P < .0001) and the CI of 1 study that contributes 29.7% to the pooled estimate does not overlap with the others. Therefore, the authors rated down 1 level due to inconsistency.

^‡‡‡

Using a threshold of 2.14% (based on 10% of the baseline risk, that is, the risk with a placebo), the lower bound of the CI suggests an important difference favoring corticosteroids and the upper bound suggests an important difference favoring no treatment (placebo). Therefore, the authors rated down 1 level due to imprecision.

Reported Adverse Effects

Infection

Twenty-one RCTs, including 1,630 participants, assessed the incidence of postoperative infection as an adverse effect at different follow-up times.^{19,22,24,28,29,31,33,35,37,38,40–47,51,54,55} The studies suggested that there may be no difference between corticosteroids and a placebo with regard to incidence of postoperative infection (risk difference, 0%; 95% CI, −1% to 1%; low certainty) (Table 2, eFigure 1, available online at the end of this article).

Alveolar osteitis

Eight RCTs, including 410 participants, examined the occurrence of alveolar osteitis as the proportion of participants experiencing this outcome at any time.^{22,24,28,37,41–43,47} Very low certainty evidence suggested that there may be no difference between corticosteroids and a placebo in terms of incidence of alveolar osteitis (risk difference, 0%; 95% CI, −3% to 4%; very low certainty) (Table 2, eFigure 2, available online at the end of this article).

GI adverse effects

Three RCTs, including 120 participants, provided evidence on the incidence of GI adverse effects expressed as the proportion of participants experiencing nausea or vomiting at any time.^27,51,52

Corticosteroids may reduce the incidence of GI adverse effects compared with a placebo; however, the evidence is uncertain (risk difference, −19%; 95% CI, −54% to 16%; very low certainty) (Table 2, eFigure 3, available online at the end of this article). In addition, although we identified a statistically significant difference in GI adverse effects depending on the route of administration (oral multidose vs submucosal single dose), the small number of events and studies did not provide compelling evidence to claim a subgroup effect (Table 2, eFigure 4, eFigure 5, available online at the end of this article).

Total pain relief, global efficacy rating, and mood alteration

None of the included studies provided evidence related to the effect of corticosteroids compared with a placebo on total pain relief, global efficacy rating, or mood alteration outcomes.

DISCUSSION

Low certainty evidence suggested that corticosteroids administered orally, submucosally, or intramuscularly in adolescent, adult, or older adult participants may decrease pain intensity a trivial amount at 6 hours compared with a placebo (no treatment with corticosteroids). This difference remained trivial at 24 hours (very low certainty). We found no difference between corticosteroids compared with a placebo with regard to the incidence of postoperative infection (low certainty) and alveolar osteitis (very low certainty). With regard to adverse events, in particular GI events (for example, nausea and vomiting), the available evidence suggested that corticosteroids could result in a small benefit (that is, a reduction in GI adverse events) compared with a placebo (very low certainty); however, these results are not trustworthy due to the small number of studies and participants. Most of the included RCTs had serious issues related to the randomization process, deviations from the intended intervention, and measurement of outcomes. In addition, none of the primary studies were conducted in the United States, where intravenous corticosteroids (not oral, submucosal, intramuscular) are often administered, patients regularly receive intravenous sedation, and more than 1 mandibular third molar may be extracted at a single appointment. To improve the certainty of the evidence, future trials should focus on conducting methodologically rigorous RCTs and increasing the sample size.

In an SR including 12 RCTs, researchers examined the impact of corticosteroids on postoperative morbidity after third-molar extraction.⁴ The researchers examined the effects of perioperative corticosteroid administration (that is, betamethasone, prednisolone, methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate, dexamethasone) on pain intensity, trismus, and swelling. Their finding suggested that corticosteroids reduced swelling and trismus in the early (1–3 days) and late (> 3 days) postoperative phases. The researchers could not determine the effect of corticosteroids on pain intensity. This differed from our findings, which suggested a negligible difference between corticosteroids and a placebo at 6 and 24 hours postoperatively. In another SR, researchers also examined the effect of corticosteroids and included 28 RCTs.⁵ The researchers concluded that corticosteroids (that is, dexamethasone, prednisolone, methylprednisolone, betamethasone) improved patients’ postoperative experiences and had a significant benefit on trismus and inflammation. As we focused our review on pain intensity and adverse effects, we did not examine the evidence regarding trismus, swelling, or inflammation; therefore, we cannot compare the results of the reviews cited above with the results of our review.

In a third SR and meta-analysis, including 8 RCTs, researchers assessed the effect of submucosal injection of dexamethasone after third-molar extraction.⁶ The results of the review suggested that the submucosal injection of dexamethasone resulted in a reduction in swelling and pain from impacted third-molar surgery. In that review, the researchers also found no difference between dexamethasone and a placebo in relation to trismus. These results are similar to those from our review in terms of reduction of pain with the use of corticosteroids.

In a fourth SR, including 7 RCTs, researchers examined the impact of different dosages of corticosteroids (that is, cortisol, prednisone, prednisolone, methylprednisolone, dexamethasone, and betamethasone) and administration routes on facial swelling, pain, and trismus.⁷ The researchers concluded that preoperative submucosal injection of corticosteroids significantly diminished facial swelling, postoperative pain, and trismus compared with a placebo. Although we did not examine facial swelling and trismus, our findings are aligned regarding pain reduction, although the magnitude of effect that we found was lower than our clinically significant threshold (10%). The researchers concluded that the optimal dosage of corticosteroids and administration route for decreasing postsurgical morbidity and improving quality of life after surgical removal of mandibular third molars was unknown.⁷

In a fifth SR, researchers analyzed the efficacy of corticosteroids for pain management after mandibular third-molar extraction.⁸ The review included 27 RCTs and the researchers concluded that corticosteroids (that is, dexamethasone, methylprednisolone, and betamethasone) could be used as an adjuvant for pain reduction after an impacted third-molar extraction. The researchers also suggested that methylprednisolone and dexamethasone delivered via an intramuscular route were the best interventions for effective pain reduction. The ideal time for administration of corticosteroids was the preoperative period. These results were similar to the results of our review in terms of reduction of pain. However, our review included dexamethasone, methylprednisolone, prednisolone, and triamcinolone acetonide and did not find a difference in pain intensity among the different corticosteroids.

The researchers in the SRs mentioned did not assess the certainty of the evidence. The results of our SR established that the best evidence supporting the outcomes of choice ranged from low through very low certainty, highlighting the need for RCTs of higher methodological and reporting quality, as well as statistical precision.

Strengths and limitations

The strengths of our review relied on each stage of the process being conducted independently and in duplicate. We assessed the risk of bias for each RCT and the certainty of the evidence for each outcome of interest. We performed the analyses and interpreted the results using the latest methodological guidance from the GRADE working group. A limitation is that we restricted our eligibility criteria to peer-reviewed research articles published in English. However, we believe it is unlikely that our conclusions would have been different had we included studies in a different language.

CONCLUSIONS

The results of our SR and meta-analysis indicated that there was low and very low certainty evidence informing the effect of corticosteroids administered orally, submucosally, or intramuscularly in adolescent, adult, or older adult participants compared with a placebo for the management of acute pain after surgical tooth extraction. Patients receiving corticosteroids in the modalities above may experience a trivial reduction in pain intensity compared with those receiving a placebo at 6- and 24-hour follow-ups; however, the evidence is uncertain. Future research should focus on examining the effect of corticosteroids on various patient-important outcomes in patients undergoing surgical tooth extractions.

Supplementary Material

NIHMS1962454-supplement-1.pdf^{(521.8KB, pdf)}

Acknowledgments

This project was financially supported by the US Food and Drug Administration, Department of Health and Human Services.

ABBREVIATION KEY

GI: Gastrointestinal
GRADE: Grading of Recommendations Assessment, Development and Evaluation
L·OVE: Living Overview of Evidence
NR: Not reported
RCT: Randomized controlled trial
SR: Systematic review

Footnotes

SUPPLEMENTAL DATA

Supplemental data related to this article can be found at: https://doi.org/10.1016/j.adaj.2023.04.018.

The findings and conclusions in this project are those of the authors and do not necessarily reflect the official views, position, or policy of, nor an endorsement by, the US Food and Drug Administration, US Department of Health and Human Services, the US government, and the American Dental Association.

Presented at the International Association for Dental Research General Session and Exhibition, June 25, 2022. https://www.iadr.org/2022iags

Disclosure. None of the authors reported any disclosures.

Contributor Information

Anna Miroshnychenko, Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada..

Maria Azab, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada, when the work described in this article was conducted. She now is a medical student, The Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada..

Sara Ibrahim, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada..

Yetiani Roldan, Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada..

Juan Pablo Diaz Martinez, Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada..

Divyalakshmi Tamilselvan, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada..

Leon He, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada, when the work described in this article was conducted. He now is a medical student, The Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada..

Olivia Urquhart, Department of Evidence Synthesis and Translation Research, American Dental Association Science and Research Institute, Chicago, IL, when part of the work described in this article was conducted. She now is an instructor, Center for Integrative Global Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA..

Francisca Verdugo-Paiva, Epistemonikos Foundation, Santiago, Chile..

Malavika Tampi, Department of Cariology, School of Dentistry, University of Michigan, Ann Arbor, MI..

Deborah E. Polk, Department of Dental Public Health, University of Pittsburgh, Pittsburgh, PA..

Paul A. Moore, Department of Dental Public Health, University of Pittsburgh, Pittsburgh, PA..

Elliot V. Hersh, Department of Oral Surgery and Pharmacology, University of Pennsylvania, Philadelphia, PA..

Romina Brignardello-Petersen, Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada..

Alonso Carrasco-Labra, Department of Evidence Synthesis and Translation Research, American Dental Association Science and Research Institute, when part of the work described in this article was conducted. He now is an associate professor, Center for Integrative Global Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA..

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40.Lim D, Ngeow WC. A comparative study on the efficacy of submucosal injection of dexamethasone versus methylprednisolone in reducing postoperative sequelae after third molar surgery. J Oral Maxillofac Surg. 2017; 75(11):2278–2286. [DOI] [PubMed] [Google Scholar]
41.Majid OW. Submucosal dexamethasone injection improves quality of life measures after third molar surgery: a comparative study. J Oral Maxillofac Surg. 2011;69(9): 2289–2297. [DOI] [PubMed] [Google Scholar]
42.Majid OW, Mahmood WK. Effect of submucosal and intramuscular dexamethasone on postoperative sequelae after third molar surgery: comparative study. Br J Oral Maxillofac Surg. 2011;49(8):647–652. [DOI] [PubMed] [Google Scholar]
43.Majid OW, Mahmood WK. Use of dexamethasone to minimise post-operative sequelae after third molar surgery: comparison of five different routes of administration. Oral Surg. 2013;6(4):200–208. [Google Scholar]
44.Mojsa IM, Pokrowiecki R, Lipczynski K, Czerwonka D, Szczeklik K, Zaleska M. Effect of submucosal dexamethasone injection on postoperative pain, oedema, and trismus following mandibular third molar surgery: a prospective, randomized, double-blind clinical trial. Int J Oral Maxillofac Surg. 2017;46(4): 524–530. [DOI] [PubMed] [Google Scholar]
45.Nair RB, Rahman NM, Ummar M. Effect of submucosal injection of dexamethasone on postoperative discomfort after third molar surgery: a prospective study. J Contemp Dent Pract. 2013;14(3):401–404. [DOI] [PubMed] [Google Scholar]
46.Pansard HB, Prado MC, Marchi GF, Sfreddo CS, Skupien JA. The impact of prior use of corticosteroid to dental extraction on oral health-related quality-of-life and clinical outcomes: a randomized clinical trial. J Oral Maxillofac Surg. 2020;78(12):2153.e1–e53.e9. [DOI] [PubMed] [Google Scholar]
47.Pedersen A Decadronphosphate in the relief of complaints after third molar surgery: a double-blind, controlled trial with bilateral oral surgery. Int J Oral Surg. 1985;14(3):235–240. [DOI] [PubMed] [Google Scholar]
48.Prashar DV, Pahwa D, Kalia V, Jindal G, Kaur R. A comparative evaluation of the effect of diclofenac sodium with and without per-orally administered methylprednisolone on the sequelae of impacted mandibular third molar removal: a cohort randomized double-blind clinical trial. Indian J Dent. 2016;7(1):11–16. [DOI] [PMC free article] [PubMed] [Google Scholar]
49.Sahu S, Patley A, Kharsan V, Madan RS, Manjula V, Tiwari RVC. Comparative evaluation of efficacy and latency of twin mix vs 2% lignocaine HCL with 1:80000 epinephrine in surgical removal of impacted mandibular third molar. J Family Med Prim Care. 2020; 9(2):904–908. [DOI] [PMC free article] [PubMed] [Google Scholar]
50.Saravanan K, Kannan R, John RR, Nantha Kumar C. A single pre operative dose of sub mucosal dexamethasone is effective in improving post operative quality of life in the surgical management of impacted third molars: a comparative randomised prospective study. J Maxillofac Oral Surg. 2016;15(1):67–71. [DOI] [PMC free article] [PubMed] [Google Scholar]
51.Schmelzeisen R, Frölich JC. Prevention of post-operative swelling and pain by dexamethasone after operative removal of impacted third molar teeth. Eur J Clin Pharmacol. 1993;44(3):275–277. [DOI] [PubMed] [Google Scholar]
52.Selimović E, Ibrahimagić-Šeper L, Šišić I, Sivić S, Huseinagić S. Prevention of trismus with different pharmacological therapies after surgical extraction of impacted mandibular third molar. Med Glas (Zenica). 2017;14(1): 145–151. [DOI] [PubMed] [Google Scholar]
53.Simone JL, Jorge WA, Horliana AC, Canaval TG, Tortamano IP. Comparative analysis of preemptive analgesic effect of dexamethasone and diclofenac following third molar surgery. Braz Oral Res. 2013;27(3): 266–271. [DOI] [PubMed] [Google Scholar]
54.Tiigimae-Saar J, Leibur E, Tamme T. The effect of prednisolone on reduction of complaints after impacted third molar removal. Stomatologija. 2010; 12(1):17–22. [PubMed] [Google Scholar]
55.Vegas-Bustamante E, Micó-Llorens J, Gargallo-Albiol J, Satorres-Nieto M, Berini-Aytés L, Gay-Escoda C. Efficacy of methylprednisolone injected into the masseter muscle following the surgical extraction of impacted lower third molars. Int J Oral Maxillofac Surg. 2008;37(3):260–263. [DOI] [PubMed] [Google Scholar]
56.Zerener T, Aydintug YS, Sencimen M, et al. Clinical comparison of submucosal injection of dexamethasone and triamcinolone acetonide on postoperative discomfort after third molar surgery. Quintessence Int. 2015;46(4): 317–326. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

NIHMS1962454-supplement-1.pdf^{(521.8KB, pdf)}

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[R52] 52.Selimović E, Ibrahimagić-Šeper L, Šišić I, Sivić S, Huseinagić S. Prevention of trismus with different pharmacological therapies after surgical extraction of impacted mandibular third molar. Med Glas (Zenica). 2017;14(1): 145–151. [DOI] [PubMed] [Google Scholar]

[R53] 53.Simone JL, Jorge WA, Horliana AC, Canaval TG, Tortamano IP. Comparative analysis of preemptive analgesic effect of dexamethasone and diclofenac following third molar surgery. Braz Oral Res. 2013;27(3): 266–271. [DOI] [PubMed] [Google Scholar]

[R54] 54.Tiigimae-Saar J, Leibur E, Tamme T. The effect of prednisolone on reduction of complaints after impacted third molar removal. Stomatologija. 2010; 12(1):17–22. [PubMed] [Google Scholar]

[R55] 55.Vegas-Bustamante E, Micó-Llorens J, Gargallo-Albiol J, Satorres-Nieto M, Berini-Aytés L, Gay-Escoda C. Efficacy of methylprednisolone injected into the masseter muscle following the surgical extraction of impacted lower third molars. Int J Oral Maxillofac Surg. 2008;37(3):260–263. [DOI] [PubMed] [Google Scholar]

[R56] 56.Zerener T, Aydintug YS, Sencimen M, et al. Clinical comparison of submucosal injection of dexamethasone and triamcinolone acetonide on postoperative discomfort after third molar surgery. Quintessence Int. 2015;46(4): 317–326. [DOI] [PubMed] [Google Scholar]

PERMALINK

Corticosteroids for managing acute pain subsequent to surgical extraction of mandibular third molars

Anna Miroshnychenko, MSc

Maria Azab, BHSc

Sara Ibrahim, BHSc

Yetiani Roldan, MD

Juan Pablo Diaz Martinez, MSc

Divyalakshmi Tamilselvan, BHSc

Leon He, BHSc

Olivia Urquhart, MPH

Francisca Verdugo-Paiva, DDS, MSc

Malavika Tampi, MPH

Deborah E Polk, PhD

Paul A Moore, DMD, PhD, MPH

Elliot V Hersh, DMD, MS, PhD

Romina Brignardello-Petersen, DDS, MSc, PhD

Alonso Carrasco-Labra, DDS, MSc, PhD

Roles

Abstract

Background.

Types of Studies Reviewed.

Results.

Practical Implications.

METHODS

Eligibility criteria

Search methods to identify and select studies

Data collection

Risk of bias in studies

Data synthesis

Certainty of the evidence

Subgroup analyses

RESULTS

Figure 1.

Characteristics of included studies

Table 1.

Risk of bias in included studies

Subgroup analyses

Figure 2.

Figure 4.

Figure 3.

Outcome measures

Corticosteroids Compared With a Placebo (No Treatment With Corticosteroids)

Postoperative pain

Table 2.

Reported Adverse Effects

Infection

Alveolar osteitis

GI adverse effects

Total pain relief, global efficacy rating, and mood alteration

DISCUSSION

Strengths and limitations

CONCLUSIONS

Supplementary Material

Acknowledgments

ABBREVIATION KEY

Footnotes

Contributor Information

References

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

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