Review Article
Efficacy of Corticosteroids on Postoperative
Endodontic Pain: A Systematic Review and
Meta-analysis
Sayna Shamszadeh, DDS,* Armin Shirvani, MD,† Mohammad Jafar Eghbal, DDS, MS,*
and Saeed Asgary, DDS, MS†
Abstract
Introduction: The purpose of this systematic review
and meta-analysis was to evaluate the effectiveness of
corticosteroids on postoperative endodontic pain and
to determine/adjust between-trial heterogeneity using
meta-regression analysis. Methods: A systematic liter-
ature search was conducted to identify randomized clin-
ical trials using corticosteroids to manage postoperative
endodontic pain in adults. The outcome measure was
pain intensity scores at 6, 12, and 24 hours postopera-
tively. Standardized mean differences (SMDs) with their
95% confidence intervals (CIs) were estimated using the
random effect inverse variance method. The level of sig-
nificance was set at P < .05. Meta-regression analysis
was also performed to examine the associations be-
tween effect sizes and study-level covariates. Results:
Eighteen randomized clinical trials, comprising 1088 pa-
tients, were included. Corticosteroids significantly reduced
the incidence of postoperative pain in endodontic patients
at 6 hours (SMD =
1.03; 95% CI,
1.55 to
0.51;
P = .000), 12 hours (SMD =
1.089; 95% CI,
1.71
to
0.46; P = .001), and 24 hours (SMD =
0.957; 95%
CI,
1.34 to
0.56; P = .000). Meta-regression analysis
showed that the type and dose of drug, performing
intention-to-treat analysis, and using rescue medication
could significantly influence the effect size at different
time points. Conclusions: Corticosteroids had a postoper-
ative pain-reducing effect in endodontic patients, and the
choice of drug regimens could be an important predictor
of pain reduction. (J Endod 2018;44:1057–1065)
Key Words
Corticosteroids, endodontics, meta-analysis, meta-
regression, postoperative pain, systematic review
From the *Dental Research Center and †Iranian Center for Endodontic Research, Research Institute of Dental Sciences, Shahid Beheshti University of Medical Science,
Tehran, Iran.
Address requests for reprints to Prof Saeed Asgary, Iranian Center for Endodontic Research, Shahid Beheshti Dental School, Daneshjou Boulevard, Evin, Tehran, Iran.
E-mail address: saasgary@yahoo.com
0099-2399/$ - see front matter
Copyright ª 2018 American Association of Endodontists.
https://doi.org/10.1016/j.joen.2018.03.010
JOE — Volume 44, Number 7, July 2018
P ostoperative pain is a
common complication
of endodontic proced-
Significance
For the first time, this meta-analysis has evaluated
the efficacy of corticosteroids on postoperative
ures, with a reported inci-
endodontic pain. Based on the included individual
dence of 3%–58% after
studies (with low to moderate risk of bias), available
root canal treatments
evidences suggest that corticosteroids might
(1). Such pain can lead
reduce the incidence of postoperative pain up to
to dissatisfaction of both
24 hours. The administration of prednisolone
patients and dental clini-
seems to result in greater pain reduction compared
cians. Thus, the manage-
with other corticosteroids.
ment of postoperative
pain is of the utmost
importance in the field of endodontics.
The most probable factor contributing to postoperative endodontic pain includes
periapical tissue irritation. It triggers a barrage of nociceptor activation and local inflam-
matory processes that lead to the release of chemical mediators, such as prostaglandins,
bradykinin, and cytokines from damaged tissues. These inflammatory mediators may in
turn activate and sensitize nociceptors, leading to peripheral sensitization (2).
Different pharmacologic strategies including nonsteroidal anti-inflammatory
drugs (NSAIDs); acetaminophen and corticosteroids have been examined to manage
postoperative endodontic pain (3). There is evidence that the use of NSAIDs and acet-
aminophen can effectively reduce postoperative endodontic pain (4). Corticosteroids
are another efficient group of drugs that function via inhibiting phospholipase A2
and leukotrienes at the site of the tissue injury (5).
The dental literature presents several clinical studies assessing the administration
of corticosteroids for the management of postoperative endodontic pain (6–8). A
previous systematic review evaluated the effect of corticosteroids on postoperative
endodontic pain and found a wide heterogeneity among selected studies. As a result,
the researchers reported that performing a meta-analysis was not possible (9).
Systematic reviews with a meta-analysis often reveal high heterogeneity of results,
which leads to a model that is not reliable in explaining the outcomes and the role of the
involved variables. A mechanism to reduce the heterogeneity of a meta-analysis is to
divide samples into subgroups according to a specific variable. However, this stratifica-
tion procedure reduces the sample size of each analysis. In meta-regression analysis,
data from different studies are pooled by accessing the effect magnitude of each variable
included in the same analysis. In this way, the role of each variable could be isolated and
adjusted to others. Meta-regression analysis is also appropriate for avoiding a stratified
meta-analysis of each variable (10).
Corticosteroids and Postoperative Endodontic Pain 1057
Review Article
The aim of the current study was to perform a meta-analysis in or-
der to assess the efficacy of corticosteroids on postoperative endodontic
pain. The study also included a coexisting object of determining/adjust-
ing between trial heterogeneity using meta-regression analysis to
examine the associations between effect sizes and study-level covariates.
Materials and Methods
The current study was performed in accordance with the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses statement
and the recommendation of the Cochrane Collaboration (11).
Selection Criteria
Studies were included if they were randomized controlled trials
(RCTs) comparing the efficacy of corticosteroids with placebo in
reducing postoperative endodontic pain. The target population was
defined as adults (>15 years old) who had undergone primary root ca-
nal therapy. The intervention was defined as different types of cortico-
steroids delivered via any route. The primary outcome was
postoperative pain intensity scores measured using the visual analog
scale at 24 hours postoperatively. Studies were excluded if they had
no placebo group or reported incomplete data.
Search Strategy
The electronic databases screened were PubMed, the Cochrane Cen-
tral Register of Controlled Trials, Scopus, Web of Science, and Google
Scholar. The searches were performed with no time and language restric-
tion up to October 2017. The following key words were used: (root canal
therapy OR endodontic) AND (postoperative pain) AND (corticosteroids).
The reference lists of the retrieved articles were additionally looked up to
identify any potential relevant article. Unpublished studies were found by
electronically searching the ProQuest Dissertation and Theses database.
Two reviewers (A.S. and S.S.) independently screened titles and
abstracts to identify potentially relevant articles. Next, the full text of
eligible articles were screened to find whether they met the selection
criteria. In case of disagreement, a third reviewer was consulted.
Data Extraction
Data from the included articles were extracted independently by 2
reviewers (A.S., and S.S.) using a customized data extraction form. Dis-
crepancies between the 2 reviewers were resolved through a discussion
with a third author. Data extracted were as follows:
1. Article identification information (authors and publication year)
2. Baseline demographic data (age, sex of participants, and preoper-
ative pulpal status)
3. Study characteristics (sample size and number of visits)
4. Intervention feature (corticosteroid regimen)
5. Outcomes of interest (postoperative pain scores and P values)
If statistical variables were shown graphically without any descrip-
tion of the original data, Adobe Photoshop software (Adobe System Inc,
San Jose, CA) was used to measure the values from the graphs.
Risk of Bias Assessment
The methodologic quality was examined using the Cochrane Col-
laboration’s Risk of Bias Assessment Tool. Domains that were assessed
are as follows:
1. Random sequence generation
2. Allocation concealment
3. Blinding of participants and personnel
4. Blinding of the outcome assessment
1058 Shamszadeh et al.
5. Incomplete outcome data
6. Selective reporting
7. Other sources of bias including group similarity, cointervention
avoided, and loss to follow-ups
Each domain was rated as ‘‘low risk,’’ ‘‘high risk,’’ or ‘‘unclear.’’
Any inconformity will be resolved by discussion.
Statistical Analysis
Meta-analysis was performed using Stata software version 12.0
(Stata Corporation, College Station, TX). Standardized mean differences
(SMDs) were used as the measures of effect size. In trials that did not
report standard deviation for the effect size calculation, we algebraically
computed equivalent effect sizes from standard error, 95% confidence
interval (CI), t statistics, or exact probability levels using approximation
methods (12). In order to include as many appropriate studies in the
meta-analysis as possible, SMDs were estimated based on the median,
range, or sample size according to the following equation:
 1=2
n1þn2
SMD ¼ t n1n2 .
If eligible studies compared different types of corticosteroids, all
types were included as separate comparisons (ie, 3-arm trials with 2
active interventions will generate 2 randomized comparisons with pla-
cebo). In this case, the numbers of participants in the placebo arms
were divided by the number of active treatment arms, thus avoiding dou-
ble counting of participants and yielding more conservative estimates.
The pooled effect was calculated using a random effect inverse
variance model. Statistical heterogeneity was assessed using the Q sta-
tistic test. The level of significance was set at P < .05.
When there was significant heterogeneity in the pooled results, we
performed random effects multivariable meta-regressions to explore
whether our estimates of treatment effects had been influenced by
explanatory covariates.
In the first model, different types of corticosteroids were fit by ad-
justing their dose to compare their efficacy at follow-ups. The second
model was planned to investigate the following covariates on the treat-
ment effect:
1. Intention-to-treat (ITT) analysis (explicitly reported vs not explicitly
reported or unclear)
2. The use of a cointervention (given vs not given rescue medication)
3. Pulp status (irreversible pulpitis vs necrosis)
4. The number of appointments (single vs multiple)
5. The route
6. The time of drug administration.
All meta-regression analyses were performed using the restricted
maximum likelihood estimate method, a recommended random effect
approach that accounts for residual between-trial heterogeneity. The
level of significance was set at P < .05.
Results
A search of the literature initially identified 205 publications. After de-
duplication, 80 articles remained. Titles and abstracts were reviewed, and
51 articles were identified as being potentially eligible at this stage. Thirty-
three studies were excluded because they did not include a randomized
double-blind study (13), did not provide appropriate treatment (14–
17), did not mention corticosteroids (18), assessed the efficacy of corti-
costeroids on the depth of anesthesia (19–21), reported postoperative
pain at the 7-day follow-up (22), had no full text available (23–25), or
JOE — Volume 44, Number 7, July 2018

did not provide appropriate statistics (26–38). The remaining 18 met the
selection criteria and were included in this meta-analysis (Fig. 1).
Study Characteristics
The characteristics of the included studies are listed in Table 1.
This review involved a total of 1028 adult patients with either a diagnosis
of irreversible pulpitis (6–8, 39–47) or pulpal necrosis (6, 7, 39, 40,
48, 49) and received either corticosteroids or placebo. The endodontic
procedure was performed in single or multiple sessions.
The corticosteroid type and dosing scheme varied between the
included studies; 7 studies used dexamethasone (dose ranging from
0.75–30 mg) (7, 8, 41, 42, 44, 47, 48), 4 used betamethasone (2
and 4 mg) (43, 49), 2 used prednisolone 30 mg (6, 39), 2 used
triamcinolone 1 mg, 1 used methylprednisolone (40), and 1 used
Meticortelone (Schering Corp, Kenilworth, NJ) (46). Corticosteroids
Figure 1. A flowchart of the search strategy.
JOE — Volume 44, Number 7, July 2018
Review Article
were administered at 3 different time periods: preoperatively
(6–8, 39, 40, 44, 47–49), intraoperatively (45, 46), or
postoperatively (41–43, 49). The drug was delivered through a
variety of routes including orally (6, 8, 39, 41–43, 47, 49),
intraligamentary (40, 44, 47), intramuscularly (47), intracanally
(45, 46), and supraperiostealy (47). In 9 trials, the patients were
instructed to take rescue medication, oral ibuprofen, and/or acetamin-
ophen when needed. Of these investigations, 4 studies excluded the pa-
tients from the trial, whereas the others did not. The visual analog score
was used for pain assessment in all studies. The follow-up periods
ranged from 6 to 24 hours postoperatively.
Risk of Bias Assessment
The risk of bias of each study is shown in Table 2. The procedure
of randomization, double blinding, and selective outcome reporting
Corticosteroids and Postoperative Endodontic Pain 1059
Review Article
TABLE 1. Characteristics of the Included Studies
Active Placebo
Reference group (n) group (n) Preoperative pulpal status Intervention used
Praveen (2017) 30 27 Vital, nonvital Preop prednisolone (30 mg) via oral route
Jalalzadeh (2010) 20 20 Vital, nonvital Preop prednisolone (30 mg) via oral route
Pochapski (2009) 25 22 Vital Preop dexamethasone (30 mg) via oral route
Kaufman (1994) 18 10 Vital, nonvital Preop methylprednisolone (8 mg) via IL route
Glassman (1989) 19 18 Vital Postop dexamethasone (4 mg) via oral route
Krasner (1986) 25 23 Vital Postop dexamethasone (0.75 mg) via oral route
Moradi (2013) 15 15 Nonvital Preop dexamethasone (4 mg) via periapical injection
Salarpoor (2013) 21 20 Vital Postop betamethasone (2 mg) via oral route
Mehrvarzfar (2008) 20 20 Vital Preop dexamethasone (8 mg) via IL route
Negm (2001) 245 230 Vital Triamcinolone (1 mg) as intracanal medicament
Eftekhar (2013) 40 40 Vital Triamcinolone (1 mg) as intracanal medicament
Zarrabi (2007) 20 20 Nonvital Preop betamethasone (2 mg) via oral route
Zarrabi (2007) 20 20 Nonvital Postop betamethasone (2 mg) via oral route
Chance (1987) 147 133 Vital Meticortelone intracanal medicament
Ahangari (2009) 20 20 Vital, nonvital Preop dexamethasone (0. 5 mg) via periapical injection
Sharma (2015) 80 20 Vital Preop dexamethasone (4 mg) via oral, IM, SP, IL routes
Shantiaee (2012) 30 30 Vital, nonvital Preop dexamethasone (4 mg) via periapical injection
Zarrabi (2003) 50 50 Vital Preop betamethasone (4 mg) via oral route
IL, intraligamentary; IM, intramuscular; Preop, preoperative; Postop, postoperative; SP, supraperiosteal.

were stated in all studies. No study reported incomplete outcome data.
Allocation concealment was not stated in any research. Five studies per-
formed ITT analysis, whereas the others did not.
Pain Scores at 6 Hours
Pain scores at 6 hours (Fig. 2) were investigated in 17 compari-
sons. Patients receiving corticosteroids reported significantly lower
pain scores compared with patients treated with placebo at 6 hours
(SMD =
1.03; 95% CI,
1.55 to
0.51; P = .000). However, the
pooled data analysis was influenced by heterogeneity (Q = 152.725,
P = .000). The meta-regression analysis found that the drug type, the
dosage of the drug (P = .00), and the use of rescue medication
(P = .01) are significant predictors of 6-hour pain scores. According
to the drug type, there was a statistically significant difference between
the following comparisons: prednisolone and betamethasone (P = .02)
and prednisolone and dexamethasone (P = .02), with superiority of
prednisolone. However, there was no significant difference between
dexamethasone and betamethasone (P = .56) (Table 3).
Pain Scores at 12 Hours
Pain scores at 12 hours (Fig. 3) were investigated in 14 compar-
isons. Patients receiving corticosteroids reported significantly lower
pain scores compared with patients treated with placebo at 12 hours
(SMD =
1.089; 95% CI,
1.71 to
0.46; P = .001). However, the
pooled data analysis was influenced by heterogeneity (Q = 141.704,
P = .000). Meta-regression showed that the type and dose of the
drug, the use of rescue medication (P = .06), and ITT analysis
(P = .03) can be significant predictors of pain scores. According to
the drug type, there was a statistically significant difference between
prednisolone and betamethasone (P = .02), with superiority of pred-
nisolone. However, there was no significant difference between dexa-
methasone and betamethasone (P = .23) (Tables 3 and 4).
Pain Scores at 24 Hours
Pain scores at 24 hours (Fig. 4) were investigated in 20 compar-
isons. Patients receiving corticosteroids reported significantly lower

TABLE 2. Risk of Bias Assessments

Lost to
Randomi- Allocation Blinding of Blinding of Incomplete Selective Group Co-intervention follow-
Reference zation concealment participants assessors outcome data reporting similarity avoided ups
Praveen (2017) + NA + +
+ +
+
Jalalzadeh (2010) + NA + +
+ + + +
Pochapski (2009) + NA + +
+ +


Kaufman (1994) + NA + +
+ + +

Glassman (1989) + NA + +
+ NA
+
Krasner (1986) + NA + +
+ NA
+
Moradi (2013) + NA + +
+ + +

Salarpoor (2013) + NA + +
+ +
+
Mehrvarzfar (2008) + NA + +
+ +


Negm (2001) + NA + +
+ +
+
Eftekhar (2013) + NA + +
+ NA +

Zarrabi (2007) + NA + +
+ NA +

Zarrabi (2007) + NA + +
+ NA +

Chance (1987) + NA + +
+ NA
+
Ahangari (2009) + NA + +
+ NA +

Sharma (2015) + NA + +
+ NA +

Shantiaee (2012) + NA + +
+ +


Zarrabi (2003) + NA + +
+ + +

+, yes;
, no; NA, not available.

1060 Shamszadeh et al. JOE — Volume 44, Number 7, July 2018

 Review Article

Figure 2. Forest plots of SMDs of corticosteroids versus placebo at 6 hours postoperatively. IL, intraligamentary; IM, intramuscular; SP, supraperiosteal.
TABLE 3. Meta-regression Analysis at Different Follow-ups (Model 1)
Follow-ups Model Covariates Coefficient (95% CI) P value
6h Comparison between dexamethasone and prednisolone with Dexamethasone 0.43 (
1.15 to 2.03) .56
betamethasone (dose adjustment) Prednisolone 4.40 (0.62–8.18) .02
Dose
0.16 (
0.27 to
0.05) .00
Constant
0.55 (
1.91 to 0.80) .39
Comparison between betamethasone and prednisolone with Prednisolone 3.96 (0.63–7.30) .02
dexamethasone (dose adjustment) Betamethasone
0.43 (
2.03 to 1.15) .56
Dose
0.16 (
0.27 to
0.05) .00
Constant
0.11 (
1.13 to 0.89) .80
Different route (oral, intraligamentary,* and PA injection) and time Oral
0.73 (
3.80 to 2.34) .61
of administration (preoperative or postoperative) PA Injection
0.35 (
3.80 to 3.08) .82
Preoperative 0.26 (
2.18 to 2.70) .81
Constant
0.87 (
4.48 to 2.74) .60
Number of visits Visit
1.19 (
2.84 to 0.45) .14
Constant 0.47 (
4.48 to 2.74) .65
12 h Comparison between dexamethasone and prednisolone with Dexamethasone 1.21 (
0.92 to 3.35) .23
betamethasone (dose adjustment) Prednisolone 3.86 (0.82–8.54) .09
Dose
1.13 (
0.27 to
0.03) .04
Constant
1.10 (
2.82 to 0.61) .18
Different route (oral, intraligamentary,* and PA injection) and time Oral
1.48 (
4.85 to 1.88) .33
of administration (preoperative or postoperative) Injection
0.55 (
4.67 to 3.55) .76
Preoperative 1.22 (
2.21 to 4.65) .43
Constant
1.16 (
5.66 to 3.33) .56
Number of visits Visit
1.41 (
4.12 to 1.28) .27
Constant 0.49 (
2.72 to 3.72) .74
24 h Comparison among dexamethasone, betamethasone, and Dexamethasone 1.19 (
1.25 to 3.65) .31
triamcinolone with prednisolone (dose adjustment) Betamethasone 1.48 (
1.46 to 4.44) .29
Triamcinolone 1.29 (
1.73 to 4.31) .37
Dose 0.04 (
0.04 to 0.14) .28
Constant
0.55 (
1.91 to 0.80) .39
Different route (oral, intraligamentary, intracanal medicament,† and Oral
1.10 (
3.52 to 1.31) .34
PA injection) and time of administration (preoperative, Injection
2.67 (
5.86 to 0.50) .09
intraoperative,‡ or postoperative) Intraligamentary
1.07 (
4.22 to 2.08) .47
Preoperative 0.50 (
1.34 to 2.35) .56
Constant
0.17 (
2.12 to 1.78) .85
Number of visits Visit
0.31 (
1.58 to 0.94) .60
Constant
0.57 (
2.39 to 1.25) .51
PA, periapical.
*The intraligamentary variable dropped because of collinearity.
†
The intacanal medicament variable dropped because of collinearity.
‡
The intraoperative variable dropped because of collinearity with the route of drug delivery.

JOE — Volume 44, Number 7, July 2018 Corticosteroids and Postoperative Endodontic Pain 1061
Review Article

Figure 3. Forest plots of SMDs of corticosteroids versus placebo at 12 hours postoperatively. IL, intraligamentary; IM, intramuscular; SP, supraperiosteal.

pain scores compared with patients treated with placebo at 24 hours use of rescue medication) could explain the heterogeneity of treat-
(SMD =
0.957; 95% CI,
1.34 to
0.56; P = .000). However, the ment effects between trials.
pooled data analysis was influenced by heterogeneity (Q = 151.469, Postoperative endodontic pain is still a common problem; it is
P = .000). Meta-regression analysis found no influence of covariates well-known that poor postoperative pain management is 1 of the
with the treatment effect at 24 hours (Table 3). predictors for successful endodontic treatment. Several studies
highlighted the role of inflammation in endodontic pain pathogen-
esis, and, thus, the application of corticosteroids with their phar-
Discussion macokinetics and pharmacodynamics (13) might be an
The present meta-analysis included 18 RCTs examining the ef- interesting option. In most included studies, corticosteroid use re-
fect of corticosteroids and placebo on postoperative pain in adults sulted in significant reductions in pain after root canal therapy.
undergoing root canal therapy. During the first 24 hours immedi- However, some investigations have reported that pain reduction
ately after endodontic treatment, corticosteroid administration re- was not significantly different between intervention and control
sulted in a significantly lower pain score versus placebo groups at 24- (8) and 48-hour (8, 38) follow-ups; this could be
administration. The studies included in the current analysis differed rational because it has been reported that the intensity of postop-
with regard to patient characteristics, corticosteroid regimens, and erative endodontic pain decreased by time (50).
methodologic design, leading to heterogeneous results. Conse- Because our results indicated that corticosteroid administration
quently, meta-regression analysis was performed, and it was found was effective for the management of postoperative endodontic pain,
that particular covariates (drug type and dosage, ITT analysis, and some dental clinicians advocated the use of corticosteroids to limit
the known predictable side effects. However, it was reported that a sin-
gle dose of corticosteroid, in the absence of contraindications, is
TABLE 4. Meta-regression Analysis of Intention-to-treat (ITT) and Use of without harmful effects (51).
Rescue Medication at Different Follow-ups (Model 2) Overall, our findings agreed with those of a recent review on the
Follow-ups Model Coefficient (95% CI) P value same topic (9); however, they did not pool the results because of clin-
ical heterogeneity among the eligible articles. Meta-analyses have been
6h Rescue
2.37 (
4.13 to
0.53) .01
medication considered reliable sources of evidence for the efficacy of treatment in
ITT analysis 1.23 (
0.34 to 2.81) .11 health care. Nevertheless, in the presence of heterogeneity, it was inap-
Constant
1.60 (
2.94 to
0.26) .02 propriate to draw conclusions from the pooled estimates of the treat-
12 h Rescue 2.56 (0.30 to 4.83) .03 ment effect (52). Meta-regression was a commonly used approach in
medication
ITT analysis
2.06 (
4.30 to 0.16) .06
meta-analysis to address the impact of covariates on study treatment ef-
Constant
3.02 (
5.10 to
0.94) .00 fects by using the regression-based method.
24 h Rescue 0.46 (
1.12 to 2.04) .54 The first major strength of our study was the performed meta-
medication analysis to provide evidence. Second, meta-regression analysis was con-
ITT analysis 0.28 (
1.31 to 1.87) .71 ducted to examine the possible sources of heterogeneity and to perform
Constant
1.32 (
2.70 to 0.05) .05
treatment comparisons among drug classes. Third, and with the excep-
CI, confidence interval. tion of 4 studies, we included all studies used for the previous review.

1062 Shamszadeh et al. JOE — Volume 44, Number 7, July 2018


Figure 4. Forest plots of SMDs of corticosteroids versus placebo at 24 hours postoperatively. IL, intraligamentary; IM, intramuscular; SP, supraperiosteal.
Three studies were not included because of incomplete outcome data.
One study was excluded because they reported pain scores after 7 days
(22). Moreover, we included 4 additional studies and thus provided ev-
idence with more power.
A considerable amount of statistical heterogeneity was explained
by the type of corticosteroid used. At 6 hours, patients achieved signif-
icantly greater pain reduction when prednisolone was compared with
dexamethasone and betamethasone. All of the mentioned drugs were
corticosteroids with an anti-inflammatory activity. Dexamethasone
and betamethasone are long-acting steroids with a biological half-life
between 36 and 72 hours, whereas prednisolone is an intermediate-
acting steroid with a half-life of 3 to 4 hours (53). The relatively higher
efficacy of prednisolone could be because of its shorter half-life when
compared with other drugs; prednisolone requires less time to diffuse
across cell membranes and alter gene transcription. Such an effect
could not be observed at other time points. This could be explained
by the fact that the intensity of postoperative endodontic pain was
decreased by time (50).
The obtained results showed that the dose of the drug might
have influenced the degree of pain reduction provided by corticoste-
roids because greater pain depletion was reported in trials investi-
gating corticosteroids with a higher dose at 6 and 12 hours
postoperatively. It is the rationale that the greater dosage did not in-
fluence the treatment effect at 24 hours because the endodontic pain
itself was reduced by time (54).
Loss to follow-up is frequent in RCTs and can be attributed to a
variety of causes. Most patients drop out of the trials because of a
lack of efficacy, adverse effects of treatment, or both (55). If noncom-
plainants and dropouts were excluded from the final analysis, it might
significantly decrease the sample size, which could lead to a decreased
statistical power (56). On the other hand, if noncomplainants and drop-
outs were mixed with complaining participants, heterogeneity might be
introduced. Thus, it was ideal to retain all participants in the study and
perform ITT analysis. A lack of such an analysis might lead to inflated
JOE — Volume 44, Number 7, July 2018
Review Article
estimates of treatment effects. This type of bias could directly affect
the results from meta-analysis, leading to inaccurate conclusions
(57). Our meta-regression analysis showed that ITT analysis could
explain some heterogeneity at 6 and 12 hours. A lack of such examina-
tions could lead to underestimation or overestimation of the treatment
effect.
Clinical trials in specific indications require the administration of
rescue medications in case a patient does not sufficiently respond to
investigational treatments. The effect of the investigational treatments
could be confounded by the additional medications (58). Our meta-
regression analysis showed that the use of rescue medications could in-
fluence the effect size at 6 and 12 hours to a degree. However, it could
not be a predictor of pain reduction at 24 hours. This could be attrib-
uted to the endodontic pain itself that reduced by time (50).
Our meta-analysis also had some potential limitations; patients
were given different types and doses of steroids, leading to marked het-
erogeneity among the included studies. Although meta-regression anal-
ysis explained certain variations between studies, some differences
might be still unclear. Another limitation was the small sample size.
In further clinical trials, close attention should be paid to more homog-
enous methodologic protocols and larger sample sizes.
It is well-known that the use of steroids suppresses the defensive
body mechanism (59). Although the literature reports that a single dose
of steroids does not have any specific harmful effects like immunosup-
pression (51), it is recommended to prescribe other classes of drugs,
such as nannarcotic analgesics, with fewer side effects. In other words,
the administration of corticosteroids should be done with caution after
weighing the risk/benefit ratio.
Because we evaluated the associations between effect sizes and
study-level covariates, we should keep in mind that meta-regression de-
scribes an observational association among included studies and there-
fore does not lend itself to demonstrate a causal relationship (60).
In conclusion, we hypothesized that the administration of cortico-
steroid drugs might be effective in reducing pain intensity in the first
Corticosteroids and Postoperative Endodontic Pain 1063
Review Article
24 hours after root canal treatment. The analgesic efficacy of corticoste-
roids can be influenced by the type and dose of the drug.
Acknowledgments
The authors thank the Iranian Center for Endodontic
Research, Research Institute of Dental Sciences, Dental School, Sha-
hid Beheshti University of Medical Sciences, Tehran, Iran, for their
support.
The authors deny any conflicts of interest related to this study.
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