Abstract
Background
Extraction of impacted third molars is a standard procedure in dentistry. However, the postoperative inflammation and pain are undesired and uncomforTable. Methylprednisolone has emerged as a possible solution to improve outcomes. This systematic review aimed to evaluate methylprednisolone in the postoperative period of impacted third molars in relation to its efficacy in postoperative pain and edema, dosage regimens, administration forms, and adverse effects.
Material and Methods
Following the PRISMA guidelines, the focus question was: “In patients who underwent impacted third molar extraction, what was the effect of methylprednisolone used postoperatively compared to non-use or the use of other medications within the same pharmacotherapeutic group to reduce inflammation and pain?” PubMed/MEDLINE and Scopus were consulted, and an additional manual was performed. The search included articles published in the last 10 years, with the language restriction to English. The articles were analyzed using the PRISMA principles, with pre-defined eligibility criteria. The data were extracted based on the general necessary information. The risk of bias for the RCTs included was performed using a revised Cochrane risk-of-bias tool for randomized trials, and a meta-analysis was performed.
Results
Nine articles were included, and five were quantitatively analyzed. Evaluating the test and control groups (methylprednisolone versus controls), there was no significant heterogeneity for pain at 24 hours (p=0.15, I²=47%) and 7 days (p=0.15, I²=47%), with non-significant effects (p=0.85). In the inter-incisal reduction, there was homogeneity at 48 hours (p=0.96, I²=0%) and 7 days (p=0.37, I²=0%), with a greater reduction in the methylprednisolone group (p<0.01 and p<0.05, respectively).
Conclusions
Methylprednisolone is efficient in safely treating patients after third molar extraction, reducing pain, edema, and trismus. It achieved better results for the inter-incisal level than dexamethasone; otherwise, dexamethasone is preferable in minimizing postoperative trismus, presenting superior potential in this specific clinical context.
Key words:Third molar, impacted teeth, methylprednisolone, corticosteroids, oral surgery.
Introduction
Third molar extractions are typically a complex procedure that requires a significant amount of time, experience, and knowledge from the professional. The location of third molars is anatomically complex due to the innervation and vascularization of these teeth. Then, post-operative sequelae, such as edema, pain, and trismus, are expected to appear immediately after surgery. Following the procedure, the worst-case scenario could include: infection, dry socket, paresthesia, and fracture (1). Usually, the referral for extraction is based on these associated pathologies. In the case of asymptomatic third molars without pathology, it is possible to monitor the patient according to the risk-benefit ratio evaluation (2,3).
Pain, trismus, and swelling are the most common postoperative complications in this type of surgery. Therefore, understanding that it is an invasive procedure, the professional must provide the patients with the most appropriate pre-, intra-, and post-operative care (2). The complications are also associated with other factors, such as the degree of tooth impaction, patient's age and health status, surgeon's experience, smoking habits, use of contraceptives, and technique used (4). Thus, there are different ways of approaching the complications depending on the type of surgery and patient.
Corticosteroids are one of the most common medications given for post-operative complications. Corticosteroids are prescribed for various conditions and have a wide range of effects on the human body. They are synthetic analogs of natural steroid hormones produced by the adrenal cortex. Their function and objective is to reduce inflammation by suppressing the immune system (5), decreasing cellular permeability and capillary dilatation by inhibiting the production of vasoactive substances and diminishing the amount of cytokines (6). Furthermore, corticosteroids repress the generation of prostaglandins, obtaining an analgesic effect (7). Corticosteroids can be divided into two groups: glucocorticoids and mineralocorticoids. Glucocorticoids have anti-inflammatory properties with minimal or no influence on the fluid or electrolyte balance (8). Regarding biodistribution, corticosteroids are immediately absorbed in the gastrointestinal tract, where they vigorously bind to proteins, undergoing hepatic metabolism and renal excretion. These drugs are available in oral, intramuscular, intravenous, intra-articular, topical, and aerosols for inhalation (9).
These drugs are also classified according to the duration of their action. Short-acting corticosteroids contain cortisone and cortisol (hydrocortisone), with an action time of less than 12 hours and an anti-inflammatory potency of one. Intermediate-acting has an action time between 12 and 36 hours; these contain prednisone and prednisolone with an anti-inflammatory potency of 4, and 6-methylprednisolone and triamcinolone have a potency of 5 and are examples of intermediate-acting drugs. Betamethasone and dexamethasone are long-acting glucocorticoids with a time of action greater than 36 hours and a potency of the anti-inflammatory character of 25 hours (10). Methylprednisolone and dexamethasone are the most often corticosteroids used after impacted third molar surgery to decrease the initial inflammatory response. These can be administered by injection into the surgical area or systemically (10,11).
Another previous systematic study (11) made the comparison between both drugs (methylprednisolone and dexamethasone); therefore, it restricted the study to those medications only. Then, the primary goal of this systematic study was to evaluate the use of methylprednisolone in the postoperative period of impacted third molars in relation to its efficacy in postoperative pain and edema, dosage regimens, forms of administration, and adverse effects. Secondarily, the aim was to analyze the impact of methylprednisolone after the extraction of impacted teeth compared to no medication use or the use of different drugs from the same pharmacotherapeutic group.
Material and Methods
This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement (12). This study was registered in PROSPERO (CRD42024512561). The PICO (Population/Intervention/Comparison/Outcome) strategy was used to formulate the clinical focus question: “In patients who underwent impacted third molar extraction (P), what was the effect of methylprednisolone used postoperatively (I) compared to non-use or the use of other medications within the same pharmacotherapeutic group (C) to reduce inflammation and pain (O)?” The outcomes observed were: (a) reduction of postoperative pain, (b) postoperative edema, (c) other complications of inflammatory origin, (d) trismus, (e) need for parallel analgesia, and (f) quality of life after extraction.
- Eligibility Criteria
The inclusion criteria were: 1. Randomized controlled trials (RCTs), 2. published within less than 10 years (2013-2023), 3. with a minimum of 10 patients, 4. published in English, and 5. reported the use of methylprednisolone in the postoperative period of extraction of impacted teeth. The exclusion were: 1. controlled clinical trials (CCTs), clinical studies, reviews, in vivo, in vitro studies, case series, and case reports, 2. studies that ignored the chronic use of medications that could interfere with the results, 3. studies that included patients with non-controllable systemic disease, 4. studies that included smokers, and 5. studies with a lack of information or detail and missing follow-up descriptions.
- Search strategy and Data extraction
Two independent investigators (HL and BL-A) performed an electronic search in the following databases: PubMed/MEDLINE and Scopus to find articles about methylprednisolone that were related to the extraction of third molars. A manual search was also performed. The combination of specific keywords was applied in each database, associated with Boolean operators: 1. PubMed/MEDLINE: (methylprednisolone) OR (corticosteroids) OR (steroids) AND ((third molar) OR (impacted teeth) OR (impacted tooth)); it was applied filters to adjust the result; 2. Scopus: (methylprednisolone) OR (corticosteroids) OR (steroids) AND ((third molar) OR (impacted teeth) OR (impacted tooth)); with filters: Limited to dentistry/limited article, clinical studies, RCT, CCT, Review, English, and 2013-2023. The agreeability inter-reviewer was assessed using Cohen’s Kappa test.
The data were extracted based on the general study design, year of publication, type of study, number of patients included, gender, age, follow-up, detail of the surgeries, dosage of the medication, drug administration route, method of swelling, maximum mouth opening (MMO) evaluation, and pain assessment.
- Quality assessment and Statistical analysis
Two reviewers (HL and BL-A) independently assessed the quality of the study; in case of disagreement, a third author (TB) was consulted. The risk of bias for the RCTs included was performed using a revised Cochrane risk-of-bias tool for randomized trials (RoB2). The following domains were observed: the randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of reported outcomes. The low risk of bias was represented by the green color and indicated that the study implemented robust measures, minimizing the risk of bias in the respective domain; uncertain risk of bias (yellow) suggested that the study lacks clear information or details, making it difficult to determine the risk of bias; high risk (red) showed the study had significant limitations or flaws in the design or execution, increasing the risk of bias. Suppose all parameters were filled with low risk (green) or until two unclear (yellow), the overall result was a low risk of bias (green). For results with only one high risk (red) and up to two unclear (yellow), the result was a moderate risk of bias. Whereas if filled with 2 or more high risks (red) and/or more than 2 unclear risks present (yellow), the overall result will be a high risk of bias (13).
The random effect model was used for the meta-analysis to evaluate the variables. Heterogeneity was analyzed using Cochran's Q test and Higgins' I2 statistics. Standardized mean differences were used to measure the effect. The statistical analyses were carried out using Review Manager 5.4 software. A comparative analysis of the studies' results was used to analyze variables where meta-analysis was not possible.
Results
The search queries identified 158 studies; 149 were excluded due to duplicates and/or did not meet the predefined eligibility criteria. These were excluded after the initial evaluation of the title and abstract. Nine articles were included for full-text analysis, resulting in the nine articles included (14-22) in this systematic review that met the eligibility criteria (k=0.92) (Fig. 1).
Figure 1.
PRISMA flowchart for the selection and inclusion of the studies.
- Study characteristics and General assessment
The data was collected and exposed in Table 1. The 9 RCTs included evaluated 354 patients, with a mean age of 25.53 years; 475 surgeries were developed. Except for Chugh et al.’s (16) and Selvaraj et al.’s (22) studies, female patients prevailed. The route of drug administration varied through oral, muscle, submucosal, or intravenous (Table 1). There was great variability in sample size, with one study having a sample of 10 patients and another with 65 patients, giving a mean value of 39.33 ± 21.18 patients per study. The average age of the patients is relatively close between the studies, except for Alcantara et al.’s (14) study, which has the lowest average value, 20.3, and Koçer et al.’s (18) study, which has the highest average value, 29.6. The number of surgeries reported in the studies varied between 20 and 104 (mean of 52.78 ± 24.06), which reveals a disparity in the number of surgeries analyzed in the studies.
Table 1.
Demographic and study design information.
| Author | Year | Type of study | nº of patients | Gender | Mean age | Follow-up | nº of surgeries | Dosage of administration (route) |
|---|---|---|---|---|---|---|---|---|
| Alcântara et al. (13) | 2014 | RCT | 16 | 3M/12F | 20.3 ±1.25 | 24h/48h/72h/7 days | 32 | Group 1: 8mg Dexamethasone (oral) Group 2: 40mg Methylprednisolone (oral) |
| Lim et al. (14) | 2017 | RCT | 65 | 11M/49FGroup 1: 3M/17F Group 2: 0M/20F Group 3: 8M/12F | Mean: 25±4 Group 1: 24.2 Group 2: 25.2 Group 3: 25.8 | 24h/48h/72h/(5/7) days | 65 | Group 1: Control (placebo) Group 2: 4mg Dexamethasone (masseter muscle) Group 3: 40mg Methylprednisolone (masseter muscle) |
| Chugh et al. (15) | 2017 | RCT | 60 | 38M/22F | 29.7 | 48h/7 days | 60 | Group 1: Control (saline solution) Group 2: 8mg Dexamethasone (submucosal) Group 3: 40mg Methylprednisolone (submucosal) |
| Srivastava et al. (16) | 2020 | RCT | 20 | 7M/13F | 26.7 | 24h/48h/72h/(4/5/7)days | 40 | Group 1: 40mg Methylprednisolone (masseter muscle) Group 2: 8mg Dexamethasone (masseter muscle) |
| Koçer et al. (17) | 2014 | RCT | 44 | 18M/26F | 29.6 | 48h/7 days | 44 | Group 1: Control Group 2: 20mg Methylprednisolone (masseter muscle) Group 3: 20mg Methylprednisolone (oral) Group 4: 20mg Methylprednisolone (intravenous) |
| Gholami et al. (18) | 2021 | RCT | 60 | 29M/31FGroup 1: 8M/12F Group 2: 13M/7F Group 3: 8M/12F | Mean: 27.55 Group 1: 27.55 Group 2: 27.25 Group 3: 25.7 | 24h (5/7) days | 60 | Group 1: 40mg Methylprednisolone (masseter muscle) Group 2: 40mg Methylprednisolone (gluteal muscle) Group 3: Control |
| Darawade et al. (19) | 2014 | RCT | 25 | NR | 25.9±6 | 24h/48h/72h/7 days | 50 | Group 1: 8mg Dexamethasone (oral) Group 2: 40mg Methylprednisolone (oral) |
| Larsen et al. (20) | 2021 | RCT | 52 | 16M/36F | 27±6 | 24h/72h/7days/1 month | 104 | Group 1: 20mg Methylprednisolone (masseter muscle) Group 2: 30mg Methylprednisolone (masseter muscle) Group 3: 40mg Methylprednisolone (masseter muscle) Group 4: Saline solution |
| Selvaraj et al. (21) | 2014 | RCT | 10 | 6M/4F | 27±6 | 48h/7 days | 20 | Group 1: 40mg Methylprednisolone (masseter muscle) Group 2: 40mg Methylprednisolone (gluteal muscle) |
NR: Not Reported; F: female; M: male.
Five studies (15,16,18,19,21) compared methylprednisolone and placebo results in the postoperative period after impacted third molars extraction. They assessed the postoperative trismus, examined the patients' range of mouth opening after impacted third molar extraction surgery, and noted any restriction in mandibular movement (subjective appraisal). In addition, those authors also evaluated the postoperative pain, measuring the intensity and duration reported. Standard pain assessment scales were used, allowing a more in-depth understanding of the effects of methylprednisolone on postoperative pain relief compared to the control/placebo group. Furthermore, the same studies also evaluated postoperative swelling, which permitted observing the facial swelling levels after extraction. The soft tissues around the surgical region were examined, noting any noticeable increase.
Five studies (14-16,20,22) compared methylprednisolone and dexamethasone in the postoperative period. Postoperative pain was assessed exclusively using the Visual Analog Scale (VAS); edema was evaluated through the presence and magnitude of its dimension; and trismus was measured through the mouth opening amplitude. These measurements were carried out using standardized assessment instruments, recording the distance between anatomical reference points in the mandible and maxilla. This assessment method allowed a quantitative analysis of trismus, providing objective data on the extent of mouth opening limitation following impacted third molar extraction.
Regarding the routes of administration for methylprednisolone in the postoperative period, three studies (23,24,27) performed the comparison. Koçer et al. (18) evaluated the oral, intravenous, and masseter routes; and Gholami et al. (19) and Selvaraj et al. (22) investigated the gluteal and masseter muscle routes. This comprehensive analysis of these studies aims to examine the relative efficacy of methylprednisolone administered by different vias, offering valuable insights for clinical practice by identifying the most effective route of administration to optimize the control of postoperative pain, edema, and trismus.
- Clinical outcomes
Table 2 shows the details of the parameters analyzed. Table 3 summarizes the inter-incisal reduction/MMO and shows the outcomes obtained comparing methylprednisolone and the control group. Koçer et al.’s (18) and Chugh's (16) results show that the experimental group had less reduction and decreased over time. On the other hand, in the 7-day results of Chugh et al. (16) and Darawade et al. (20), the average reduction was higher in the experimental group. Table 3 summarizes the studies that reported results on inter-incisal reduction using only methylprednisolone (single group).
Table 2.
Clinical outcomes design.
| Author | Swelling assessment | MMO | Pain assessment |
|---|---|---|---|
| Alcântara et al. (13) | Sum of the three measurements (corner of the eye/angle of the mandible-tragus/corner of the mouth-tragus/pogonion) | Reduction in MMO from baseline value | VAS score (0-10) |
| Lim et al. (14) | Sum of 2 lines-corner of the eye to angle and tragus to corner of mouth. Measure as % change in baseline value. Reported in graphical data only | Maximum interincisal distance between pre-operative and post-operative days | VAS score (0-10) |
| Chugh et al. (15) | Sum of 2 lines-corner of the eye to angle and tragus to corner of mouth. Measure as mean change in base value in mm | Reduction in MMO from baseline value | VAS score (0-10) |
| Srivastava et al. (16) | Lines: Tragus-Commissure + Gonion-external canthus + gonion-commissure | Reduction in MMO from baseline value | VAS score (0-10) |
| Koçer et al. (17) | Lines: Canthus-gnathion line; tragus-commissure line; tragus-pogonion | The distance between the upper and lower incisal borders of the central incisors was measured using a digital caliper | NR |
| Gholami et al. (18) | Measured by ultrasound imaging | Maximum interincisal distance between pre-operative and post-operative days | VAS score (0-10) |
| Darawade et al. (19) | Tape measuring method described by Ustun et al. | Measure of the distance between the right upper and lower central incisors with the help of a caliper | VAS score (0-10) |
| Larsen et al. (20) | NR | Maximum interincisal distance between pre-operative and post-operative days | VAS score (0-100) |
| Selvaraj et al. (21) | Distance between tragus-lip commissure, gonion-lip commissure and gonion-external canthus of the eye using surgical silk thread | Measured with Caprovich callipers | VAS score (0-100) |
MMO: Maximum mouth opening; NR: Not Reported.
Table 3.
Summary of studies on inter-incisal reduction.
| Author | Administration route | Dose (mg) | Control (mm) | Methylprednisolone (mm) | |||||
|---|---|---|---|---|---|---|---|---|---|
| Average (48h) | Average (7d) | nº | Average (48h) | Average (7d) | nº | ||||
| MMO | Koçer et al. (a) | Oral | 20 | 17.5 | 11.1 | 11 | 13.3 | 5.1 | 11 |
| Koçer et al.(b) | IV | 20 | 17.5 | 11.1 | 11 | 8 | 1.7 | 11 | |
| Koçer et al. (c) | Muscular (masseter) | 20 | 17.5 | 11.1 | 11 | 7.7 | 1.6 | 11 | |
| Chugh et al. | Submucosal | 40 | 7.2±4.54 | 1.4±2.45 | 17 | 5.5±4.73 | 1.7±3.09 | 23 | |
| Darawade et al.(a) | Muscular (masseter) | 40 | NR | 3.55 | 20 | NR | 8 | 20 | |
| Darawade et al.(b) | Muscular (gluteal) | 40 | NR | 3.55 | 20 | NR | 6.33 | 20 | |
| MMO (Methylprednisolone - single group) | Selvaraj et al.(a) | Muscular (masseter) | 40 | - | - | - | NR | 10.8 | 4.7 |
| Selvaraj et al. (b) | Muscular (gluteal) | 40 | - | - | - | NR | 11.1 | 3.3 | |
| Alcantara et al. | Oral | 40 | - | - | - | 16.27±8.13 | 19.97±7.88 | 6.47±4.32 | |
| Lim et al. | Submucosal | 40 | - | - | - | 8 | 7 | 2 | |
| Srisvastava et al. | Muscular (masseter) | 40 | - | - | - | NR | 15.85 | 7.15 | |
| Darawade et al. | Oral | 40 | - | - | - | 14.64±7.30 | 17.97±7.09 | 5.82±3.88 | |
NR: Not reported; IV: intravenous; MMO: Maximum mouth opening; h: hours; d: days.
Comparing methylprednisolone and dexamethasone (Table 4), the pain increased over time in both groups in the Alcantara et al. study (14); in the Srivastava et al. (17) and Darawade et al. (20) studies, it decreased in the methylprednisolone group and remained the same in the dexamethasone group over time.
Table 4.
Overview and summary of pain, edema (Tragus-Commissure), and edema (Canthus-Gnathion).
| Author | Administration route | Dose (mg) | Dexamethasone (mm) - Pain Control (mm) - Edema | Methylprednisolone (mm) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Preop. | Average (1st period) | Average (2nd period) | nº | Preop. | Average (1st period) | Average (2nd period) | nº | ||||
| Pain (1st period: 24h/ 2nd period: 48h) | Alcantara et al. | Oral | 40 | - | 2 | 4 | 16 | - | 1 | 2 | 16 |
| Srivastava et al. | Muscular (masseter) | 40 | - | 7±6.60 | 6±6.05 | 10 | - | 7±6.80 | 7±6.45 | 10 | |
| Chugh et al. | Submucosal | 40 | - | 5.3±3.25 | NR | 23 | - | 3.5±3.13 | NR | 20 | |
| Darawade et al. | Oral | 40 | - | 2.5 | 1.5 | 25 | - | 1.5 | 1.5 | 25 | |
| Edema (Tragus-Commissure) (1st period: 48h/ 2nd period: 7d) | Koçer et al. (a) | Oral | 20 | 114 | 126.4 | 120.6 | 11 | 114 | 123.0 | 117.5 | 11 |
| Koçer et al. (b) | IV | 20 | 114 | 126.4 | 120.6 | 11 | 116.6 | 122.4 | 117.3 | 11 | |
| Koçer et al. (c) | Muscular (masseter) | 20 | 114 | 126.4 | 120.6 | 11 | 111.2 | 114.6 | 111.6 | 11 | |
| Edema (Canthus-Gnathion) (1st period: 48h/ 2nd period: 7d) | Koçer et al.(a) | Oral | 20 | 92 | 98.3 | 95.1 | 11 | 99.6 | 103.6 | 100.5 | 11 |
| Koçer et al.(b) | IV | 20 | 92 | 98.3 | 95.1 | 11 | 109.6 | 112.8 | 110.3 | 11 | |
| Koçer et al. (c) | Muscular (masseter) | 20 | 92 | 98.3 | 95.1 | 11 | 101.9 | 102.9 | 101.9 | 11 | |
NR: Not reported; Preop.: preoperatively; IV: intravenous; d: days; h: hours; mm: millimeters.
For the swelling analysis, Table 4 show the results for Tragus-Commissure and Canthus-Gnathion edema, respectively, reported in Koçer et al.'s study (18). For Tragus-Commissure, the experimental group has lower average values than the control group in all three studies, and in both groups, the results decrease over time. For Canthus-Gnathion, the experimental group showed higher results on average than the control group in all three studies; in both groups, the results decreased over time.
- Quality assessment and Statistical analysis
Fig. 2 presents the risk of bias for the included RCTs. Three studies had a low risk of bias, 2 had a moderate risk, and 4 had a high risk. Due to limitations in the included literature, the meta-analysis was only done for specific parameters. The careful selection of parameters was based on the availability and comparability of data, guaranteeing the robustness and validity of the results obtained.
Figure 2.
Overall Risk of Bias Assessment using RoB2 tool.
Fig. 3 shows the pain results after 24 hours and 7 days, comparing the result of methylprednisolone with placebo (control). After 24 hours, Cochran's Q (p=0.15>0.05) and I2=47%, it was observed moderate heterogeneity; the forest plot shows that the effect of the meta-analysis 0.05 (95%CI [-0.45;0.55]) was not statistically significant (p=0.85). After 7 days, the forest plot showed the effect of the meta-analysis -0.08 (95%CI [-0.58;0.42]), which was also not statistically significant (p=0.85). Analyzing the data for the comparison between methylprednisolone and dexamethasone, Cochran's Q (p=0.31>0.05) and I2=3%, it was concluded there was homogeneity between studies after 24 hours; the forest plot shows that the effect of the meta-analysis 0.37 (95%CI [-0.14;0.88]) was not statistically significant (p=0.16).
Figure 3.
Meta-analysis results for pain after (A) 24h and (B) 7 days comparing methylprednisolone with placebo, and (C) after 24h comparing methylprednisolone with dexamethasone.
Fig. 4 shows the inter-incisal/MMO reduction results at 48 hours and 7 days. Given the results, Cochran's Q (p=0.96>0.05) and I2=0% (A) and Q (p=0.37>0.05) and I2=0% (B), it was concluded that there was homogeneity between studies about inter-incisal/MMO reduction at 48 hours and 7 days. The forest plot presented the most significant reduction occurred in the methylprednisolone group, and the effect was 0.65 (95%CI [0.29;1.01]) (A) and 0.44 (95%CI [0.09;0.80]) (B), respectively, statistically significant result (p<0.01 and p<0.05).
Figure 4.
Meta-analysis results for inter-incisal reduction after 48 hours (A) and after 7 days (B).
Discussion
The aim of this systematic review was to assess the effect of methylprednisolone in patients undergoing third molar surgery, with a specific focus on post-operative trismus, pain, and edema. This analysis was carried out considering the predefined criteria, grouping all available randomized controlled trials (RCTs) that investigated the use of methylprednisolone in comparison with a control group, as well as in comparison with dexamethasone.
For the dosage of corticosteroids to be effective, it must exceed the physiological production of the human body (5-30mg/day) (23). The doses used in this review were 20 mg and 40 mg. The results of this review showed that methylprednisolone was efficient in reducing pain, edema, and trismus. It is similarly observed in the literature, where the corticosteroids, e.g., dexamethasone and methylprednisolone, showed the ability to inhibit the immune system. It is an anti-inflammatory with analgesic and anti-allergic potential. Moreover, the toxicology proved that both are safe at low dosages via oral or other use routes (24). Therefore, careful instructions should be passed to the patients when using glucocorticoids.
The literature has shown that methylprednisolone, at standard doses, was considered more effective than dexamethasone and prednisolone for treatments (25) and five times more potent than hydrocortisone (26). It suggests that methylation of prednisolone makes it more potent by aiding interaction with a cellular target rather than increasing its stability. Otherwise, the long-term use of these medications and when used in high dosages, may cause some undesired side effects (steroid osteoporosis, steroid diabetes, delayed wound healing, and are closely associated with mortality) (27). Methylprednisolone exhibited linear plasma protein binding (average of 77%) and was moderately distributed into tissue spaces; however, the volume of distribution of prednisolone is only one-half that of methylprednisolone, proving the superiority of this drug (28).
Within this context, the results of the present review revealed after 48 hours and 7 days that dexamethasone had lower inter-incisal/MMO reduction compared to methylprednisolone (respectively, p<0.01 and p<0.05). Agrawal et al.'s (29) results agree with the evidence presented herein, reinforcing the efficacy of corticosteroids. This consistency strengthens the evidence of the positive potential of corticosteroids in mitigating postoperative trismus, providing additional support for their effectiveness in promoting a more comforTable and effective recovery after third molar surgery (30).
Regarding pain, after 24 hours, there was no significant effect between methylprednisolone and dexamethasone (p=0.16). This highlights the complexity of post-operative pain, which is influenced by different factors such as surgical trauma and the individual inflammatory response and threshold. Variability in pain administration and measurement methods between studies may also have contributed to these results. Furthermore, the prophylactic oral intake of dexamethasone 8 mg was compared to 4 mg to verify the control of the postsurgical edema after third molar extractions; 8 mg presented greater efficacy in the control of postsurgical edema (31). The literature also suggests other medications, such as the postoperative administration of 30 mg prednisolone; it demonstrated relief for trismus, swelling, and pain compared to non-steroidal anti-inflammatory (NSAI) (control group); this fact shows the potential of prednisolone. There was a significant reduction of swelling (p<0.05) and higher MMO and visual analogue scale (VAS) for the use of prednisolone, without any disturbance of wound healing or other corticosteroid-related complications (32). In addition, another medication typically prescribed is ibuprofen (NSAI). Ibuprofen and methylprednisolone are the two drugs largely used in this type of surgery (third molar extraction) (2); Schultze-Mosgau et al. (33) showed that the combination of both medications allowed to obtain better analgesic and anti-inflammatory effects than the separate use. López Carriches et al. compared methylprednisolone and diclofenac in reducing trismus (34). Similarly, Bamgbose et al. also verified the absence of differences in the control of trismus when they compared a group medicated with dexamethasone and diclofenac versus using only diclofenac (35). On the other hand, the results obtained by Troullos et al. supported the existence of differences between the tested groups, with considerably lower trismus values in patients medicated with methylprednisolone compared to those medicated with ibuprofen (36).
Comparing the methylprednisolone with the control groups included, the pain parameter was observed after 24 hours and 7 days; in both periods, no significant effect was observed in favor of methylprednisolone (p=0.85). This suggests that methylprednisolone may not be more effective than the control assessed in reducing pain at these time intervals. However, it is essential to consider that postoperative pain is a subjective experience and can be influenced by various factors (such as the type of surgery performed, the patient's psychological state, the presence of pre-existing conditions, the quality of pain management, and the level of social support) (37). Subgroup analyses may provide additional insights into the efficacy of methylprednisolone in different populations and surgical contexts (18). Another study (38) also reported no significant differences in pain between the groups treated with methylprednisolone and the control groups at the same period. These results highlight the need to consider postoperative pain as a multifaceted experience influenced by a variety of factors and the importance of more detailed analyses to understand the effects of methylprednisolone on postoperative pain management fully.
In 2023, a systematic study (11) recently compared methylprednisolone versus dexamethasone's efficacy in managing post-surgical pain, swelling, and trismus after surgery. Some methodological differences were observed compared to our study: 1. the present systematic study compared the results of methylprednisolone with any other medication or no medication, while the other systematic included articles that performed only the comparison between dexamethasone versus methylprednisolone; 2. the authors included other databases besides what was used in the present study, which can obtain a different inclusion; 3. the authors considered articles published without publication date or language restrictions, whereas the present study included some limitations (articles published in the last 10 years [2013-2023] and English language); and 4. there was differences in the eligibility criteria comparing both systematic studies. Otherwise, a similar result was found for dexamethasone, which had statistically significant and better results than methylprednisolone in reducing trismus.
- Limitations of the Study
As a limitation, it is possible to verify that a low number of RCTs have been developed on the subject. Also, many of the articles needed to have more crucial values. Several studies did not report complete measurements, and many did not include standard deviations, which made it impossible to include these studies in the meta-analysis. In addition, the divergence in the measures used between the different studies represented a significant challenge. For example, when assessing trismus, we opted to use the inter-incisal reduction measure since most of the available articles employed this specific method, providing greater consistency and comparability between studies. However, when trying to convert data from articles that measured maximum mouth opening to the inter-incisal reduction measure, we often lost the standard deviation value, making it impossible to calculate this crucial statistic for the meta-analysis accurately. Similarly, there was significant variability in the measurement methods used between the different studies in assessing edema. This methodological heterogeneity and the lack of reported standard deviations made it difficult to harmonize the data, limiting the possibility of carrying out a comprehensive and comparative meta-analysis.
- Final considerations
Within the limitations of this study, it was possible to verify that methylprednisolone efficiently treats patients safely after third molar extraction, reducing pain, edema, and trismus. There was a positive trend for edema reduction via masseter muscle; however, there was no significant difference or comparable data available regarding pain, the best route of administration, adverse effects, and patient post-operative comfort. Methylprednisolone achieved better inter-incisal level/MMO results than dexamethasone; otherwise, dexamethasone is preferable in minimizing postoperative trismus, presenting superior potential in this specific clinical context. All data should be carefully analyzed due to the study's limitations, the small number of studies included, heterogeneity found, and the risk of bias present. More RCT studies are recommended to confirm the findings of this study.
Acknowledgement
Declared none.
Institutional Review Board Statement
Declared none.
Author Contributions
Conceptualization, HL, TB, MP, BL-A; methodology, HL, TB, MP, BL-A; software, HL, TB, MP, WR, JCHF, GVOF, BL-A; validation, HL, TB, MP, BL-A; formal analysis, HL, TB, MP, WR, JCHF, GVOF, BL-A; investigation, HL, TB, MP, WR, JCHF, GVOF, BL-A; resources, HL, TB, MP, WR, JCHF, GVOF, BL-A; data curation, HL, TB, MP, WR, JCHF, GVOF, BL-A; writing-original draft preparation, HL, TB, MP, WR, JCHF, GVOF, BL-A; writing-review and editing, HL, TB, MP, WR, JCHF, GVOF, BL-A; visualization, HL, TB, MP, GVOF, BL-A; supervision, TB, MP, BL-A; project administration, TB, MP, BL-A. All authors have read and agreed to the published version of the manuscript.
Funding
None.
Conflict of interest
The authors declare no conflict of interest, financial or otherwise.
References
- 1.Bamgbose BO, Akinwande JA, Adeyemo WL, Ladeinde AL, Arotiba GT, Ogunlewe MO. Effects of co-administered dexamethasone and diclofenac potassium on pain, swelling and trismus following third molar surgery. Head Face Med. 2005;1:1–6. doi: 10.1186/1746-160X-1-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Osunde OD, Ra A, Uk O. Management of inflammatory complications in third molar surgery: A review of the literature. Afr Health Sci. 2011;11:530–7. [PMC free article] [PubMed] [Google Scholar]
- 3.Marciani RD. Is there pathology associated with asymptomatic third molars? J Oral Maxillofac Surg. 2012;70:S15–9. doi: 10.1016/j.joms.2012.04.025. [DOI] [PubMed] [Google Scholar]
- 4.Dudde F, Giese M, Schuck O, Krüger C. Impacted third molar surgery in older patients-Is patient's age really a risk factor for complications? Clin Oral Investig. 2024;28:576. doi: 10.1007/s00784-024-05975-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Prado CE, Crowe SF. Corticosteroids and cognition: A meta-analysis. Neuropsychol Rev. 2019;29:288–312. doi: 10.1007/s11065-019-09405-8. [DOI] [PubMed] [Google Scholar]
- 6.Montgomery MT, Hogg JP, Roberts DL, Redding SW. The use of glucocorticosteroids to lessen the inflammatory sequelae following third molar surgery. J Oral Maxillofac Surg. 1990;48:179–87. doi: 10.1016/s0278-2391(10)80207-1. [DOI] [PubMed] [Google Scholar]
- 7.Hargreaves KM, Costello A. Glucocorticoids suppress levels of immunoreactive bradykinin in inflamed tissue as evaluated by microdialysis probes. Clin Pharmacol Ther. 1990;48:168–78. doi: 10.1038/clpt.1990.132. [DOI] [PubMed] [Google Scholar]
- 8.Ngeow WC, Lim D. Do corticosteroids still have a role in the management of third molar surgery? Adv Ther. 2016;33:1105–39. doi: 10.1007/s12325-016-0357-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Kapugi M, Cunningham K. Corticosteroids. Orthop Nurs. 2019;38:336–9. doi: 10.1097/NOR.0000000000000595. [DOI] [PubMed] [Google Scholar]
- 10.Larsen MK, Kofod T, Christiansen AE, Starch-Jensen T. Different dosages of corticosteroid and routes of administration in mandibular third molar surgery: a systematic review. J Oral Maxillofac Res. 2018;9:e1. doi: 10.5037/jomr.2018.9201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Singh A, Pentapati KC, Kodali MVRM, Smriti K, Patil V, Chowdhary GL. Efficacy of Preemptive Dexamethasone versus Methylprednisolone in the Management of Postoperative Discomfort and Pain after Mandibular Third Molar Surgery: A Systematic Review and Meta-Analysis. Sci World J. 2023;2023:7412026. doi: 10.1155/2023/7412026. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Syst Rev. 2021;10:89. doi: 10.1186/s13643-021-01626-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Rondone EM, Leitão-Almeida B, Pereira MS, Fernandes GVO, Borges T. The Use of Tissue Grafts Associated with Immediate Implant Placement to Achieve Better Peri-Implant Stability and Efficacy: A Systematic Review and Meta-Analysis. J Clin Med. 2024;13:821. doi: 10.3390/jcm13030821. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Alcântara CEP, Falci SGM, Oliveira-Ferreira F, Santos CRR, Pinheiro MLP. Pre-emptive effect of dexamethasone and methylprednisolone on pain, swelling, and trismus after third molar surgery: a split-mouth randomized triple-blind clinical trial. Int J Oral Maxillofac Surg. 2014;43:93–8. doi: 10.1016/j.ijom.2013.05.016. [DOI] [PubMed] [Google Scholar]
- 15.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;75:2278–86. doi: 10.1016/j.joms.2017.05.033. [DOI] [PubMed] [Google Scholar]
- 16.Chugh A, Singh S, Mittal Y, Chugh V. Submucosal injection of dexamethasone and methylprednisolone for the control of postoperative sequelae after third molar surgery: randomized controlled trial. Int J Oral Maxillofac Surg. 2018;47:228–33. doi: 10.1016/j.ijom.2017.07.009. [DOI] [PubMed] [Google Scholar]
- 17.Srivastava N, Shetty A, Kumar P, Rishi D, Bagga V, Kale SG. Comparison of Preemptive Effect of Dexamethasone and Methylprednisolone After Third Molar Surgery: A Split-Mouth Randomized Triple-Blind Clinical Trial. J Maxillofac Oral Surg. 2021;20:264–70. doi: 10.1007/s12663-020-01346-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Koçer G, Yuce E, Oncul AT, Dereci O, Koskan O. Effect of the route of administration of methylprednisolone on oedema and trismus in impacted lower third molar surgery. Int J Oral Maxillofac Surg. 2014;43:639–43. doi: 10.1016/j.ijom.2013.11.005. [DOI] [PubMed] [Google Scholar]
- 19.Gholami M, Anbiaee N, Abad SBMF, Asadi M. What are the effects of methylprednisolone injection into the masseter and gluteal muscle on pain, edema and trismus after impacted lower third molar surgery? A randomized clinical trial. J Oral Maxillofac Surg. 2021;79:1829–36. doi: 10.1016/j.joms.2021.03.006. [DOI] [PubMed] [Google Scholar]
- 20.Darawade DA, Kumar S, Mehta R, Sharma AR, Reddy GS. In search of a better option: dexamethasone versus methylprednisolone in third molar impaction surgery. J Int Oral Health. 2014;6:14–7. [PMC free article] [PubMed] [Google Scholar]
- 21.Larsen MK, Kofod T, Duch K, Starch-Jensen T. Efficacy of methylprednisolone on pain, trismus and quality of life following surgical removal of mandibular third molars: a double-blind, split-mouth, randomised controlled trial. Med Oral Patol Oral Cir Bucal. 2021;26:e156–63. doi: 10.4317/medoral.24094. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Selvaraj L, Rao SH, Lankupalli AS. Comparison of Efficacy of Methylprednisolone Injection into Masseter Muscle Versus Gluteal Muscle for Surgical Removal of Impacted Lower Third Molar. J Maxillofac Oral Surg. 2014;13:495–8. doi: 10.1007/s12663-013-0562-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.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;49:647–52. doi: 10.1016/j.bjoms.2010.09.021. [DOI] [PubMed] [Google Scholar]
- 24.Mehta J, Rolta R, Mehta BB, Kaushik N, Choi EH, Kaushik NK. Role of Dexamethasone and Methylprednisolone Corticosteroids in Coronavirus Disease 2019 Hospitalized Patients: A Review. Front Microbiol. 2022;13:813358. doi: 10.3389/fmicb.2022.813358. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Sari A, Ekinci O, Saraçoglu KT, Balik R, Aslan M, Balik Y. A Comparison of the Effects of Dexamethasone and Methylprednisolone, Used on Level-3 Intensive Care COVID-19 Patients, on Mortality: A Multi-Center Retrospective Study. J Korean Med Sci. 2023;38:e232. doi: 10.3346/jkms.2023.38.e232. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Mico-Llorens JM, Satorres-Nieto M, Gargallo-Albiol J, Arnabat-Dominguez J, Berini-Aytes L, Gay-Escoda C. Efficacy of methylprednisolone in controlling complications after impacted lower third molar surgical extraction. Eur J Clin Pharmacol. 2006;62:693–8. doi: 10.1007/s00228-006-0164-5. [DOI] [PubMed] [Google Scholar]
- 27.Hwang JL, Weiss RE. Steroid-induced diabetes: a clinical and molecular approach to understanding and treatment. Diabetes Metab Res Rev. 2014;30:96–102. doi: 10.1002/dmrr.2486. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Szefler SJ, Ebling WF, Georgitis JW, Jusko WJ. Methylprednisolone versus prednisolone pharmacokinetics in relation to dose in adults. Eur J Clin Pharmacol. 1986;30:323–9. doi: 10.1007/BF00541537. [DOI] [PubMed] [Google Scholar]
- 29.Agrawal A, Chandel S, Singh N, Tiwari AK, Singh AK, Singh G. The efficacy of intralesional dexamethasone versus intravenous dexamethasone in surgery for impacted third molars: A randomized controlled trial. Natl J Maxillofac Surg. 2020;11:94–97. doi: 10.4103/njms.NJMS_46_17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Yadav R, Verma U, Tiwari R, Article O. Heterogeneous conceptualization of etiopathogenesis: Oral pyogenic granuloma. Natl J Maxillofac Surg. 2019;10:3–7. doi: 10.4103/njms.NJMS_55_18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Filho JRL, Maurette PE, Allais M, Cotinho M, Fernandes C. Clinical comparative study of the effectiveness of two dosages of Dexamethasone to control postoperative swelling, trismus and pain after the surgical extraction of mandibular impacted third molars. Med Oral Patol Oral Cir Bucal. 2008;13:E129–32. [PubMed] [Google Scholar]
- 32.Tiigimae-Saar J, Leibur E, Tamme T. The effect of prednisolone on reduction of complaints after impacted third molar removal. Stomatologija. 2010;12:17–22. [PubMed] [Google Scholar]
- 33.Schultze-Mosgau S, Schmelzeisen R, Frolich JC, Schmele H. Use of ibuprofen and methylprednisolone for the prevention of pain and swelling after removal of impacted third molars. J Oral Maxillofac Surg. 1995;53:2–8. doi: 10.1016/0278-2391(95)90486-7. [DOI] [PubMed] [Google Scholar]
- 34.Carriches CL, Martinez Gonzalez JM, Rodriguez MD. The use of methylprednisolone versus diclofenac in the treatment of inflammation and trismus after surgical removal of lower third molars. Med Oral Patol Oral Cir Bucal. 2006;11:E440–5. [PubMed] [Google Scholar]
- 35.Bamgbose BO, Akinwande JA, Adeyemo WL, Ladeinde AL, Arotiba GT, Ogunlewe MO. Effects of co-administered dexamethasone and diclofenac potassium on pain, swelling and trismus following third molar surgery. Head Face Med. 2005;1:11. doi: 10.1186/1746-160X-1-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Troullos ES, Hargreaves KM, Butler DP, Dionne RA. Comparison of nonsteroidal anti-inflammatory drugs, ibuprofen and flurbiprofen, with methylprednisolone and placebo for acute pain, swelling, and trismus. J Oral Maxillofac Surg. 1990;48:945–52. doi: 10.1016/0278-2391(90)90007-o. [DOI] [PubMed] [Google Scholar]
- 37.Khorshidi R, Maghsood K, Ayda P, Saadat P, Khiavi G. Pain control following impacted third molar surgery with bupivacaine irrigation of tooth socket: a prospective study. J Dent Res Dent Clin Dent Prospect. 2010;4:105–9. doi: 10.5681/joddd.2010.027. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Markiewicz MR, Brady MF, Ding EL, Dodson TB. Corticosteroids reduce postoperative morbidity after third molar surgery: a systematic review and meta-analysis. J Oral Maxillofac Surg. 2008;66:1881–94. doi: 10.1016/j.joms.2008.04.022. [DOI] [PubMed] [Google Scholar]